AU4031700A - Low adenosine anti-sense oligonucleotide, compositions, kit and method for treatment of airway disorders associated with bronchoconstriction, lung inflammation,allergy(ies) and surfactant depletion - Google Patents

Description

WO 00/62736 PCT/USOO/08020 LOW ADENOSINE ANTI-SENSE OLIGONUCLEOTIDE, COMPOSITIONS, KIT & METHOD FOR TREATMENT OF AIRWAY DISORDERS ASSOCIATED WITH BRONCHOCONSTRICTION, LUNG INFLAMMATION, ALLERGY(IES) & SURFACTANT DEPLETION 5 BACKGROUND OF THE INVENTION Field of the Invention This patent relates to a composition comprising oligonucleotides (oligos) that are anti-sense to adenosine receptors, and contain low amounts of or no adenosine (A). These agents are suitable for the treatment, among others, of pulmonary diseases associated with inflammation, impaired airways, 10 including lung disease and diseases whose secondary effects afflict the lungs of a subject. Examples of these diseases are allergies, asthma, impeded respiration, allergic rhynitis, pain, cystic fibrosis, and cancers such as leukemias, e.g. colon cancer, and the like. The present agent may be administered prophylactically or therapeutically in conjunction with other therapies, or may be utilized as a substitute for therapies that have significant, negative side effects. 15 Background of the Invention Respiratory ailments, associated with a variety of diseases and conditions, are extremely common in the general population, and more so in certain ethnic groups, such as African Americans. In some cases they are accompanied by inflammation, which aggravates the condition of the lungs. Asthma, for example, is one of the most common diseases in industrialized countries. In the United 20 States it accounts for about 1% of all health care costs. An alarming increase in both the prevalence and mortality of asthma over the past decade has been reported, and asthma is predicted to be the preeminent occupational lung disease in the next decade. While the increasing mortality of asthma in industrialized countries could be attributable to the depletion reliance upon beta agonists in the treatment of this disease, the underlying causes of asthma remain poorly understood. 25 Adenosine may constitute an important mediator in the lung for various diseases, including bronchial asthma. Its potential role was suggested by the finding that asthmatics respond favorably to aerosolized adenosine with marked bronchoconstriction whereas normal individuals do not. An asthmatic rabbit animal model, the dust mite allergic rabbit model for human asthma, responded in a similar fashion to aerosolized adenosine with marked bronchoconstriction whereas non-asthmatic 30 rabbits showed no response. More recent work with this animal model suggested that adenosine induced bronchoconstriction and bronchial hyperresponsiveness in asthma may be mediated primarily through the stimulation of adenosine receptors. Adenosine has also been shown to cause adverse effects, including death, when administered therapeutically for other diseases and conditions in subjects with previously undiagnosed hyper reactive airways. 35 A handful of medicaments have been available for the treatment of respiratory diseases and conditions, although in general they all have limitations. Theophylline, an important drug in the treatment of asthma, is a known adenosine receptor antagonist which was reported to eliminate adenosine-mediated bronchoconstriction in asthmatic rabbits. A selective adenosine A, receptor antagonist, 8-cyclopentyl-1, 3-dipropylxanthine (DPCPX) was also reported to inhibit adenosine 40 mediated bronchoconstriction and bronchial hyperresponsiveness in allergic rabbits. The therapeutic and preventative applications of currently available. adenosine A, receptor-specific antagonists are, nevertheless, limited by their toxicity. Theophylline, for example, has been widely used in the treatment of asthma, but is associated with frequent, significant toxicity resulting from its narrow therapeutic dose range. DPCPX is far too toxic to be useful clinically. The fact that, despite decades of 45 extensive research, no specific adenosine receptor antagonist is available for clinical use attests to the general toxicity of these agents. Anti-sense oligonucleotides have received considerable theoretical consideration as potential useful pharmacological agents in human disease. Their practical application in actual models of human disease, however, has been somewhat elusive. One important impediment to their effective application has been a difficulty in finding an appropriate route of administration to WO 00/62736 2 PCT/USOO/08020 deliver them to their site of action. Many in vivo experiments were conducted by administering anti sense oligonucleotides directly to specific regions of the brain. These applications, however, necessarily have limited clinical utility due to their invasive nature. Although anti-sense oligonucleotides have received considerable theoretical consideration for their potential use as 5 pharmacological agents in human disease, finding practical and effective applications for these agents in actual models of human disease, however, have been few and far between, particularly because they had to be administered in large doses. Another important consideration in the pharmacologic application of these molecules is their route of administration. Many in vivo applications have involved the direct administration of anti-sense oligonucleotides to limited regions of the brain. Such 10 applications, however, have limited clinical utility due to their invasive nature. The systemic administration of anti-sense oligonucleotides as pharmacological agents has been found to have also significant problems, not the least of which being an inherent difficulty in targeting disease-involved tissues. That is, the necessary dilution of the anti-sense oligonucleotide in the circulatory system makes extremely difficult to attain a therapeutic dose at the target tissue by intravenous or oral administration. 15 The bioavailability of orally administered anti-sense oligonucleotides is very low, of the order of less than about 5%. Anti-sense oligonucleotides have been used in therapy by many, including the present inventor, who in his previous work successfully treated various diseases and conditions by direct administration of these agents to the lung. In many instances, other workers have had to face the difficulties associated with the delivery of DNA molecules to a desired target. Thus, the route of 20 administration may be of extreme importance for treating generalized diseases and conditions as well as those which are localized. In contrast, up to the present time, the delivery of anti-sense agents to the lung has been relatively undeveloped. As described by the present inventor in more detail below, the lung is an excellent target for the direct administration of anti-sense oligonucleotides and provides a non-invasive and a tissue-specific route. 25 Clearly, there exist presently no effective therapies for treating these ailments, or at least no therapies which are effective and devoid of significant detrimental side effects. Accordingly, there is still a need for an agent for the treatment of adenosine mediated ailments afflicting the pulmonary and respiratory ailments affecting the lung airways, including respiratory problems, bronchoconstriction, inflammation, allergy(ies), depletion or hyposecretion of surfactant, etc., which is highly effective and 30 sufficiently selective to avoid detrimental side effects produced by other therapies. In addition, there is a definite need for making available a delivery method that will require low amounts of therapeutic agents and will be effective for the rapid and targeted access of tissue genes of mRNAs and the reversal of untoward effects afflicting a subject. SUMMARY OF THE INVENTION 35 The present invention generally relates to a pharmaceutical or veterinary composition, comprising an anti-sense oligonucleotide(s) (oligo(s)) which is (are) effective for alleviating bronchoconstriction and/or lung inflammation, allergy(ies), and\or surfactant depletion and\or hyposecretion, when administered to a mammal, the oligo containing about 0 to about 15% adenosine (A) and being anti-sense to a target selected from the group consisting of the initiation codon, the 40 coding region, the 5'-end and the 3'-end genomic flanking regions, the 5' and 3' intron-exon junctions, and regions within 2 to 10 nucleotides of the junctions of a gene encoding a target polypeptide associated with lung airway dysfunction or anti-sense to the polypeptide mRNA; combinations of the oligos; and mixtures of the oligos; and a pharmaceutically or veterinarily acceptable carrier or diluent. The targets are typically molecules associated with airway disease, cancer, etc., such as transcription 45 factors, stimulating and activating peptide factors, cytokines, cytokine receptors, chemokines, chemokine receptors, adenosine receptors, bradykinin receptors, endogenously produced specific and non-specific enzymes, immunoglobulins and antibodies, antibody receptors, central nervous system (CNS) and peripheral nervous and non-nervous system receptors, CNS and peripheral nervous and non-nervous system peptide transmitters, adhesion molecules, defensins, growth factors, vasoactive 50 peptides and receptors, binding proteins, and malignancy associated proteins, among others. Examples WO 00/62736 PCT/USOO/08020 3 are oligo(s) targeted to adenosine receptor(s) and it(they) are typically present in the composition in an amount effective to reduce adenosine mediated effect(s), such as airway obstruction, inflammation, allergy(ies), and sufactant depletion, among others. The adenosine receptor is preferably selected from the group consisting of the adenosine A 1 , A 2 b, and A 3 receptors, and in some instances even adenosine 5 A, receptors. The oligo of the invention may be applied to the preparation of a medicament for (a) reducing adenosine-mediated bronchoconstriction, impeded respiration, inflammation, allergy(ies), depletion production of surfactant, and other detrimental pulmonary effects in a subject in need of treatment, and/or for (b) treating specific diseases and conditions such as asthma, cystic fibrosis, allergic rhynitis, COPD, etc. For the first time this invention provides the targeted administration of 10 one or more oligonucleotides directly into the repiratory system. The oligos may be directed to any target and are intended for fast delivery through the mucosal tissue of the lungs for hybridization to a desired target polynucleotide, e. g. mRNA, to prevent gene transcription and translation, such that protein expression will be reduced, hampered, or completely stopped. Thus, this invention also provides a more general method for administering oligonucleotides that are anti-sense to targeted genes 15 and mRNAs associated with any type of diseases, by direct administration into the respiratory system, e. g. by inhalation, by introduction of a solution or aerosol into the respiratory airways, and/or directly into the lung. The present oligos, moreover, are suitable for reducing effects mediated by a variety of target proteins and genes, for example adenosine-mediated effects, including pulmonary, respiratory, and 20 other associated effects, e. g. bronchoconstriction, inflammation, immune mediated reactions, allergy(ies) and other airway problems, which may be caused by different conditions, including cancer. Examples of diseases and conditions, which may be treated preventatively, prophylactically and therapeutically with the agent of this invention, are pulmonary vasoconstriction, inflammation, allergies, asthma, impeded respiration, respiratory distress syndrome, pain, cystic fibrosis, allergic 25 rhynitis, pulmonary hypertension, pulmonary vasoconstriction, emphysema, chronic obstructive pulmonary disease (COPD), bronchitis, and cancers such as leukemias, lymphomas, carcinomas, and the like, e.g. colon cancer, breast cancer, lung cancer, pancreatic cancer, hepatocellular carcinoma, kidney cancer, melanoma, hepatic metastases, etc., as well as all types of cancers which may metastasize or have metastasized to the lung(s), including breast and prostate cancer. The present 30 agents are also suitable for administration before, during and after other treatments, including radiation, chemotherapy, antibody therapy, phototherapy and cancer, and other types of surgery. The present agent is effectively administered prophylactically and therapeutically in conjunction with other therapies, or by itself for conditions without known therapies or as a substitute for therapies that have significant negative side effects. The oligo(s) may be administered by any means known to a subject, 35 e. g. to the lungs of the subject, more generally through any and all systemic and topical routes. This oligonucleotide(s) (oligo(s)) employed are anti-sense to to a target DNA or RNA, e. g. an adenosine receptor DNA or RNA, and preferably consist essentially of up to about 15% adenosine (A), and more preferably contain no adenosine. The oligos are provided in the form of specific compositions and formulations, with a carrier or diluent, and optionally with other therapeutic agents and additives which 40 are used for administration by specific routes, e.g. into the respiratory system, topically, transdermally, parenterally, by implantation, and the like. The oligo is also provided as a capsule or cartridge, and in the form of a kit. The oligos of the invention may be produced by selection of specific targeted segments of the gene or mRNA encoding the adenosine receptor as described below. In one preferred embodiment, the selection is made to obtain oligos that consisting essentially of less than about 15% 45 adenosine (A). This may be done by selecting the target as done above, which includes genes, genomic flanking regions, RNAs and polypeptide associated with an ailment afflicting the lung airways, obtaining the sequence of a mRNA(s) corresponding to the target gene(s) and/or their genomic flanking region(s) and/or the juxta-membrane regions thereof, and mRNA(s) encoding the target polypeptide(s), selecting at least one segment of the mRNA(s), and synthesizing one or more anti-sense 50 oligonucleotide(s) to the selected mRNA segment(s), and substituting, if necessary, an alternative, e. g.

WO 00/62736 PCT/USOO/08020 4 a universal base(s) or other base(s) for one or more A to reduce the proportion of A present in the oligonucleotide to less than about 15%, and down to no adenosine. Similarly, alternative and/or universal bases may be substituted for adenosine, e. g. specific adenosine Al, A2b and A3 receptor antagonists or A2a receptor agonists, theophilline, enprophylline, and many other adenosine receptor 5 antagonists known in the art as well as agonists with significantly reduced agonist activity with respect to adenosine, e. g. less than 0.5%, less than 0.3%, and the like. The invention will now be described in general in conceptual and experimental terms, with reference to specific examples. Other objects, advantages and features of the present invention will become apparent to those skilled in the art from the description that follows. 10 DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS This invention arose from a desire by the inventor to improve on prior art treatments for pulmonary and other diseases, which technology is generally frought with detrimental side effects and by the need of administering high doses of therapeutical agents. The present invention arises from the inventor's own discovery that adenosine receptor targeted anti-sense oligonucleotides (oligos) may be 15 utilized therapeutically in the treatment of diseases or conditions which impair respiration, cause inflammation and/or allergy(ies), constrict bronchial tissue, obstruct the lung airways, depletion surfactant secretion, or otherwise impede normal breathing. In general, many diseases and conditions are associated with or cause inflammation, constrict bronchial tissue or the lung airways, depletion secretion of surfactant, augment allergy(ies), or otherwise impede normal breathing. This treatment is 20 selective for specific targets associated with or mediating these symptoms, and the agents are administered in up to 1000-fold lower doses than those seen in the art. The inventor, in addition, wanted to provide a treatment which would improve the outcome and life style of patients undergoing other procedures or being administered other therapies, including antibody therapy, chemotherapy, radiation, phototherapy, and surgery e.g. cancer surgery, and that could be effectively administered 25 preventatively, prophylactically or therapeutically. He reasoned that he could further improve on this discovery by selecting oligos of reduced adenosine content, or reducing the adenosine content of otherwise targeted anti-sense oligos corresponding to endogenous polynucleotide sequences: The present invention is premised on the discovery by the inventor that oligonucleotides are metabolized in vivo to their mononucleotides. Adenosine (A)-containing oligonucleotides break down and release 30 adenosine which, in turn, activates adenosine receptors, thereby causing bronchoconstriction, inflammation, surfactant depletion, allergy(ies), and the like. He, thus, conceived of employing low adenosine-free adenosine oligos to avoid these side effects upon their administration. He succeeded in this endeavor and is providing in this patent novel and improved compositions, formulations and methods which afford greatly improved results when compared with previously known treatments for 35 preventing and alleviating bronchoconstriction, allergy(ies), inflammation, breathing difficulties, surfactant depletion and blockage of airways, as well as for other conditions which affect the lung directly or indirectly. In different embodiments, one or more nucleic acids of the invention may be formulated alone, and/or with one or more surfactant components and/or with a carrier, and/or with other therapeutic agents and/or formulation agents known in the art. The compositions of this 40 invention, thus, may be incorporated into a variety of formulations for systemic and topical administration. Moreover, the inventor also provides a broad method for delivery of anti-sense oligonucleotides (oligos) through the respiratory system, as a fast means of starting treatment to address acute attacks of asthma and other diseases and conditions that have a rapid onset. In addition, the present agents have long halflives and may be administered at very low doses. This makes them 45 ideal for once a week type therapies. In the past, anti-sense oligonucleotides received considerable theoretical consideration as being potentially useful as pharmacologic agents for the treatment of human disease. Wagner, R., Nature 372: 333-335 (1994). However, it has been difficult to actually apply these molecules to alleviating and curing human diseases. One important consideration in the pharmacologic application of these molecules has been the failure of various routes of administration 50 to deliver the compounds to its target while avoiding invading the circulation and, therefore, other WO 00/62736 PCT/USOO/08020 5 untargeted tissues which, thus, produces a plethora of side effects. Most in vivo experiments utilizing anti-sense oligonucleotides involved a direct application of the oligo to limited regions of the brain. See, Wahlestedt, C., Trends in Pharmacol. Sci. 15: 42-46 (1994); Lai, J. et al., Neuroreport 5: 1049 1052 (1994); Standifer, K., et al., Neuron 12: 805-810 (1994); Akabayashi, A., et al., Brain Res. 21: 5 55-61 (1994). Others applied them into the spinal fluid. See, e.g. Tseng, L., et al., European J. Pharmacol. 258: R1-3 (1994); Raffa, R., et al., European J. Pharmacol. 258: R5-7 (1994); Gillardon, F., et al., European J. Neurosci. 6: 880-884 (1994). Such applications, clearly, have no practical clinical utility due to their invasive nature. Thus, the systemic administration of anti-sense oligonucleotides poses significant problems with respect to their pharmacologic application, not the 10 least of which is the difficulty in selectively targeting disease-involved tissues. The systemic administration of anti-sense oligonucleotides also poses significant problems with respect to their pharmacologic application, not the least of which is the difficulty in selectively targeting disease involved tissues. The respiratory system, and in particular the lung, as the ultimate port of entry into the 15 organism, however, is an excellent route of administration for anti-sense oligonucleotides. This is so not only for the treatment of lung disease, but also when utilizing the lung as a means for delivery, particularly because of its non-invasive and tissue-specific nature. Thus, local delivery of antisense oligonucleotides directly to the target tissue enables the therapeutic use of these compounds. Fomivirsen (ISIS 2302) is an example of a local drug delivery into the eye to treat cytomegalovirus 20 (CMV) retinitis, for which a new drug application has been filed by ISIS. The administration of a drug through the lung offers the further advantage that inhalation is non-invasive whereas direct injection in to the vitreous of the eye is invasive. The composition and formulations of this invention are highly efficacious for preventing and treating diseases and conditions associated with bronchoconstriction, difficult breathing, impeded and obstructed lung airways, allergy(ies), inflammation and surfactant 25 depletion, among others. Examples of diseases and conditions which are suitably treated by the present method are diseases and conditions, including Acute Respiratory Distress Syndrome (ARDS), asthma, adenosine administration e.g. in the treatment of SupraVentricular Tachycardia (SVT) and other arrhythmias, and in stress tests to hyper-sensitized individuals, ischemia, renal damage or failure induced by certain drugs, infantile respiratory distress syndrome, pain, cystic fibrosis, pulmonary 30 hypertension, pulmonary vasoconstriction, emphysema, chronic obstructive pulmonary disease (COPD), lung transplantation rejection, pulmonary infections, and cancers such as leukemias, lymphomas, carcinomas, and the like, including colon cancer, breast cancer, lung cancer, pancreatic cancer, hepatocellular carcinoma, kidney cancer, melanoma, hepatic metastases, etc., as well as all types of cancers which may metastasize or have metastasized to the lung(s), including breast and 35 prostate cancer. The invention will be described with respect to the adenosine receptors as targets, but is similarly applicable to any other target with respect to the pulmonary administration of anti-sense oligos. The examples provided below show a complete inhibition of such adenosine receptor associated symptoms in a rabbit model for human bronchoconstriction, allergy(ies) and inflammation as well as the elimination of the ability of the adenosine receptor agonist par excellence, adenosine, to 40 cause bronchoconstriction in hyper-responsive monkeys, which are animal models for human hyper responsiveness to adenosine receptor agonists. The pharmaceutical composition and formulations of the invention, therefore, are suitable for preventing and alleviating the symptoms associated with stimulation of adenosine receptors, such as the adenosine A, receptors. The compositions and formulations of this invention, thus, are also suitable for prevent the untoward side effects of 45 adenosine-mediated hyperresponsiveness in certain individuals, which are generally seen in diseases affecting respiratory activity. The method of the present invention may be used to treat airway diseases and conditions in a subject of any kind and for any reason, with the intention that the adenosine content of anti-sense compounds be minimized, reduced or eliminated so as to prevent its liberation upon anti-sense 50 degradation. Examples of diseases and conditions, which may be treated preventatively, WO 00/62736 PCT/USOO/08020 6 prophylactically and therapeutically with the compositions and formulations of this invention, are pulmonary vasoconstriction, inflammation, allergies, asthma, allergic rhynitis, impeded respiration, Acute Respiratory Distress Syndrome (ARDS), renal damage and failure associated with ischemia as well as the administration of certain drugs, side effects associated with adenosine administration e.g. in 5 SupraVentricular Tachycardia (SVT) and in adenosine stress tests, infantile Respiratory Distress Syndrome (infantile RDS), ARDS, pain, cystic fibrosis, pulmonary hypertension, pulmonary vasoconstriction, emphysema, chronic obstructive pulmonary disease (COPD), lung transplantation rejection, pulmonary infections, and cancers such as leukemias, lymphomas, carcinomas, and the like, e.g. colon cancer, breast cancer, lung cancer, pancreatic cancer, hepatocellular carcinoma, kidney 10 cancer, melanoma, metastatic cancer such as hepatic metastases, lung, breast and prostate metastases, among others. The present compositions and formulations are suitable for administration before, during and after other treatments, including radiation, chemotherapy, antibody therapy, phototherapy and cancer, and other types of surgery. The present compositions and formulations may also be administered effectively as a substitute for therapies that have significant negative side effects.The 15 terms "anti-sense" oligonucleotides generally refers to small, synthetic oligonucleotides, resembling single-stranded DNA, which in this patent are applied to the inhibition of gene expression by inhibition of a target messenger RNA (mRNA). See, Milligan, J. F. et al., J. Med. Chem. 36(14), 1923-1937 (1993), the relevant portion of which is hereby incorporated in its entirety by reference. For consistency=s sake, all RNAs and oligonucleotides are represented in this patent by a single strand in 20 the 5' to 3' direction, when read from left to right, although their complementary sequence(s) is (are) also encompassed within the four corners of the invention. In addition, all nucleotide bases and amino acids are represented utilizing the recommendations of the IUPAC-IUB Biochemical Nomenclature Commission, or by the known 3-letter code (for amino acids). Nucleotide sequences are presented herein by single strand only, in the 5' to 3' direction, from left to right. In addition, nucleotide and 25 amino acids are represented herein in the manner recommended by the IUPAC-IUB Biochemical Nomenclature Commission, or (for amino acids) by three letter code, in accordance with 37 CFR ' 1.822 and established usage. See, e.g., PatentIn User Manual, 99-102 (Nov. 1990) (U.S. Patent and Trademark Office, Office of the Assistant Commissioner for Patents, Washington, D.C. 20231); U.S. Patent No. 4,871,670 to Hudson et al. at col. 3, lines 20-43. The present method utilizes anti-sense 30 agents to inhibit or down-regulate gene expression of target genes, including those listed in Tables 1 and 2 below. This is generally attained by hybridization of the anti-sense oligonucleotides to coding (sense) sequences of a targeted messenger RNA (mRNA), as is known in the art. The exogenously administered agents of the invention decrease the levels of mRNA and protein encoded by the target gene and/or cause changes in the growth characteristics or shapes of the thus treated cells. See, 35 Milligan et al. (1993); Helene, C. and Toulme, J. Biochim. Biophys. Acta 1049, 99-125 (1990); Cohen, J. S. D., Ed., Oligodeoxynucleotides as Anti-sense Inhibitors of Gene Expression; CRC Press: Boca Raton, FL (1987), the relevant portion of which is hereby incorporated in its entirety by reference. As used herein, "anti-sense oligonucleotide or asnti-sense oligo" is generally a short sequence of synthetic nucleotide that (1) hybridizes to any segment of a mRNA encoding a targeted protein under 40 appropriate hybridization conditions, and which (2) upon hybridization causes a decrease in gene expression of the targeted protein. The terms "desAdenosine" (desA) and "des-thymidine" (desT) refer to oligonucleotides substantially lacking either adenosine (desA) or thymidine (desT). In some instances, the des A or des T sequences are naturally occurring, and in others they may result from substitution of an undesirable nucleotide (A) by another lacking its undesirable activity, such as acting 45 as an agonist or having a triggering effect at the adenosine A receptor(s). In the present context, the substitution is generally accomplished by substitution of A with a "universal or alternative base", presently known in the art or to be ascertained at a later time. As used herein, the terms "prevent", "preventing", "treat" or "treating" refer to a preventative, prophylactic, maintenance, or therapeutic treatment which decreases the likelihood that the subject administered such treatment will manifest 50 symptoms associated with adenosine receptor stimulation. The term "down-regulate" refers to inducing WO 00/62736 PCT/USOO/08020 7 a decrease in production, secretion or availability and, thus, a decrease in concentration, of intracellular target product, be it a receptor e. g. adenosine A 1 , A 2 b, A 3 , bradykinin 2B, GATA-3, or other receptors, or an increase in concentration of the adenosine A2a receptor. The present technology relies on the design of anti-sense oligos targeted to mRNAs associated with ailments involving lung airway 5 pathology(ies), and on their modification to reduce the occurrence of undesirable side effects caused by their release of adenosine upon breakdown, while preserving their activity and efficacy for their intended purpose. In this manner, the inventor targets a specific gene to design one or more anti-sense oligonucleotide(s) (oligos) that selectively bind(s) to the corresponding mRNA, and then reduces, if necessary, their content of adenosine via substitution with an alternative or a universal base, or an 10 adenosine analog incapable of significantly, or having substantially reduced ability for, activating or antagonizing adenosine A, A 2 b or A, receptors or which may act as an agonist at the adenosine A 2 a, receptor. Any number of adenosines present may be substituted by an alternative and/or universal base, such as heteroaromatic bases, which binds to a thymidine base but has less than about 0.3 of the adenosine base agonist or antagonist activity at the adenosine A 1 , A 2 a, A 2 b and A 3 receptors. Based on 15 his prior experience in the field, the inventor reasoned that in addition to "downregulating" specific genes, he could increase the effect of the agent(s) administered by either selecting segments of RNA that are devoid, or have a low content, of thymidine (T) or, alternatively, substitute one or more adenosine(s) present in the designed oligonucleotide(s) with other nucleotide bases, so called universal bases, which bind to thymidine but lack the ability to activate adenosine receptors and otherwise 20 exercise the constricting effect of adenosine in the lungs, etc. Given that adenosine (A) is a nucleotide base complementary to thymidine (T), when a T appears in the RNA, the anti-sense oligo will have an A at the same position. In one aspect of this invention, the anti-sense oligonucleotide has a sequence which specifically binds to a portion or segment of a mRNA molecule which encodes a protein associated 25 with impeded breathing, allergy(ies), lung inflammation, depletion of lung surfactant or lowering of lung surfactant, airway obstruction, bronchitis, and the like. One effect of this binding is to reduce or even prevent the translation of the corresponding mRNA and, thereby, reduce the available amount of target protein in the subject-s lung. In one preferred embodiment of this invention, the phosphodiester residues of the anti-sense oligonucleotide are modified or substituted. Chemical analogs of 30 oligonucleotides with modified or substituted phosphodiester residues, e.g., to the methylphosphonate, the phosphotriester, the phosphorothioate, the phosphorodithioate, or the phosphoramidate, a= methoxy ethyl and similar modifications, which increase the in vivo stability of the oligonucleotide are particularly preferred. The naturally occurring phosphodiester linkages of oligonucleotides are susceptible to some degree of degradation by cellular nucleases. Many of the residues proposed herein, 35 on the contrary, are highly resistant to nuclease degradation. See, Milligan et al.; Cohen, J. S. D., supra. In another preferred embodiment of the invention, the oligonucleotides may be protected from degradation by adding a "3'-end cap" by which nuclease-resistant linkages are substituted for phosphodiester linkages at the 3' end of the oligonucleotide. See, Tidd, D. M. and Warenius, H.M., Be. J. Cancer 60: 343-350 (1989); Shaw, J.P. et al., Nucleic Acids Res. 19: 747-750 (1991), the relevant 40 section of which are incorporated in their entireties herein by reference. Phosphoramidates, phosphorothioates, and methylphosphonate linkages all function adequately in this manner for the purposes of this invention, as do a' modifications, such as a' methoxy ethyl, and the like. The more extensive the modification of the phosphodiester backbone the more stable the resulting agent, and in many instances the higher their RNA affinity and cellular permeation. See, Milligan, et al., supra. In 45 addition, a plurality of substitutions to the carbohydrate ring are also known to improve stability of nucleic acids. Thus, the number of residues which may be modified or substituted will vary depending on the need, target, and route of administration, and may be from 1 to all the residues, to any number in between. Many different methods for replacing the entire phosphodiester backbone with novel linkages are known. See, Millikan et al, supra. Preferred backbone analogue residues include phosphoramidate, 50 phosphorothioate, methylphosphonate, phosphorotriester, phosphotriester, thioformacetal, WO 00/62736 PCT/USOO/08020 8 phosphorodithioate, phosphoramidate, formacetal, triformacetal, thioether, carbamate, boranophosphate, 3'-thioformacetal, 5'-thioether, carbonate, C 5 -substituted nucleotides, 5'-N carbamate, sulfate, sulfonate, sulfamate, sulfonamide, sulfone, sulfite, 2'-O methyl, sulfoxide, sulfide, hydroxylamine, methylene(methylimino) (MMI), methoxymethyl (MOM), and methoxyethyl(MOE), 5 and methyleneoxy(methylimino) (MOMI) residues, and combinations thereof. Phosphorothioate and methylphosphonate-modified oligonucleotides are particularly preferred due to their availability through automated oligonucleotide synthesis. See, Millikan et al, supra. Where appropriate, the agent of this invention may be administered in the form of their pharmaceutically acceptable salts, or as a mixture of the anti-sense oligonucleotide and its salt. In another embodiment of this invention, a 10 mixture of different anti-sense oligonucleotides or their pharmaceutically acceptable salts is administered. A single agent of this invention has the capacity to attenuate the expression of a target mRNA and/or various agents to enhance or attenuate the activity of a pathway. By means of example, the present method may be practiced by identifying all possible deoxyribonucleotide segments which are low in thymidine (T) or deoxynucleotide segments low in adenosine (A) of about 7 or more 15 mononucleotides, preferably up to about 60 mononucleotides, more preferably about 10 to about 36 mononucleotides, and still more preferably about 12 to about 21 mononucleotides, in a target mRNA or a gene, respectively. This may be attained by searching for mononucleotide segments within a target sequence which are low in, or lack thymidine (RNA), a nucleotide which is complementary to adenosine, or that are low in adenosine (gene), that are 7 or more nucleotides long. In most cases, this 20 search typically results in about 10 to 30 such sequences, i.e. naturally lacking or having less than about 40% adenosine, anti-sense oligonucleotides of varying lengths for a typical target mRNA of average length, i.e., about 1800 nucleotides long. Those with high content of T or A, respectively, may be fixed by substitution of a universal base for one or more As. The agent(s) of this invention may be of any suitable length, including but not limited to, about 7 to about 60 nucleotides long, preferably 25 about 12 to about 45, more preferably up to about 30 nucleotides long, and still more preferably up to about 21, although they may be of other lengths as well, depending on the particular target and the mode of delivery. The agent(s) of the invention may be directed to any and all segments of a target RNA. One preferred group of agent(s) includes those directed to an mRNA region containing a junction between an intron and an exon. Where the agent is directed to an intron/exon junction, it may 30 either entirely overlie the junction or it may be sufficiently close to the junction to inhibit the splicing out of the intervening exon during processing of precursor mRNA to mature mRNA, e.g. with the 3' or 5' terminus of the anti-sense oligonucleotide being positioned within about, for example, within about 2 to 10, preferably about 3 to 5, nucleotide of the intron/exon junction. Also preferred are anti-sense oligonucleotides which overlap the initiation codon, and those near the 5' and 3' termini of the coding 35 region. The flanking regions of the exons may also be targeted as well as the spliced segments in the precursor mRNAs. The mRNA sequences of the adenosine receptors and of many other targets are derived from the DNA base sequence of the gene expressing either receptors, e. g. the adenosine receptors, the enzymes, factors, or other targets associated with airway disease. For example, the sequence of the genomic human A, adenosine receptor is known and is disclosed in U.S. Patent No. 40 5,320,963 to Stiles, G., et al. The A, adenosine receptor has been cloned, sequenced and expressed in rat (see, Zhou, F., et al., P.N.A.S. (USA) 89: 7432 (1992)) and human (see, Jacobson, M. A., et al., U.K. Patent Application No. 9304582.1 (1993)). The sequence of the adenosine A 2 b receptor gene is also known. See, Salvatore, C. A., Luneau, C. J., Johnson, R. G. and Jacobson, M., Genomics (1995), the relevant portion of which is hereby incorporated in its entirety by reference. The sequences of 45 many of the remaining exemplary target genes are also known. See, GenBank, NIH. The sequences of those genes whose sequences are not yet available may be obtained by isolating the target segments applying technology known in the art. Once the sequence of the gene, its RNA and/or the protein are known, an anti-sense oligonucleotides may be produced according to this invention as described above to reduce the production of the targeted protein in accordance with standard techniques. The sequences 50 for the adenosine Ala bradykinin, and other genes as well as methods for preparation of WO 00/62736 PCT/USOO/08020 9 oligonucleotides are also known as those of many other target genes and mRNAs for which this invention is suitable. Thus, anti-sense oligonucleotides that downregulate the production of target sequences associated with airway disease, including the adenosine A 1 , Ala, A 2 b, A 3 , bradykinin, GATA 3, COX-2, and many other receptors, may be produced in accordance with standard techniques. 5 Examples of diseases and conditions which are suitably treated by the present method are diseases and conditions, including Acute Respiratory Distress Syndrome (ARDS), asthma, adenosine administration e.g. in the treatment of SupraVentricular Tachycardia (SVT) and other arrhythmias, and in stress tests to hyper-sensitized individuals, ischemia, renal damage or failure induced by certain drugs, infantile respiratory distress syndrome, pain, cystic fibrosis, pulmonary hypertension, pulmonary 10 vasoconstriction, emphysema, chronic obstructive pulmonary disease (COPD), pulmonary transplantation rejection, pulmonary infections, and cancers such as leukemias, lymphomas, carcinomas, and the like, including colon cancer, breast cancer, lung cancer, pancreatic cancer, hepatocellular carcinoma, kidney cancer, melanoma, hepatic metastases, etc., as well as all types of cancers which may metastasize or have metastasized to the lung(s), including breast and prostate 15 cancer. The adenosine receptors discussed above are mere examples of the high power of the inventors technology. In fact, a large number of genes may be targeted in a similar manner by the present agent(s), to reduce or down-regulate protein expression. By means of example, if the target disease or condition is one associated with impeded or reduced breathing, bronchoconstriction, chronic 20 bronchitis, pulmonary bronchoconstriction and/or hypertension, chronic obstructive pulmonary disease (COPD), pulmonary transplantation rejection, pulmonary infections, allergy, asthma, cystic fibrosis, respiratory distress syndrome, cancers, which either directly or by metastasis afflict the lung, the present method may be applied to a list of potential target mRNAs, which includes the targets listed in Table 1 and Table 2 below, among others. The anti-sense agent(s) of the invention have a low A 25 content to prevent its liberation upon in vivo degradation of the agent(s). For example, if the system is the pulmonary or respiratory system, a large number of genes is involved in different functions, including those listed in Table 1 below. Table 1: Pulmonary Disease or Condition Pulmonary and Inflammation Targets Nf6B Transcription Factor Interleukin-8 Receptor (IL-8 R) 30 Interleukin-5 Receptor (IL-5R) Interleukin-4 Receptor (IL-4R) Interleukin-3 Receptor (IL-3R) Interleukin- 1 P (IL-i ) Interleukin- lP Receptor (IL-i IR) Eotaxin Tryptase Major Basic Protein P2-adrenergic Receptor Kinase Endothelin Receptor A 35 Endothelin Receptor B Preproendothelin Bradykinin B2 Receptor (B2BR) IgE (High Affinity Receptor) Interleukin- 1 (IL-1) Interleukin 1 Receptor (IL-I R) Interleukin-9 (IL-9) Interleukin-9 Receptor (IL-9 R) Interleukin- 11 (IL-11) Interleukin- 11 Receptor (IL-11 R) 40 Inducible Nitric Oxide Synthase Cyclooxygenase (COX) Intracellular Adhesion Molecule 1 (ICAM- 1) Vascular Cellular Adhesion Molecule Substance P (VCAM) Rantes Endothelial Leukocyte Adhesion Molecule Endothelin ETA Receptor (ELAM-i) 45 Cyclooxygenase-2 (COX-2) GM-CSF, Endothelin-l Monocyte Activating Factor Neutrophil Chemotactic Factor Neutrophil Elastase 'Defensin 1,2,3 Muscarinic Acetylcholine Receptors Platelet Activating Factor Tumor Necrosis Factor a 5-lipoxygenase 50 Phosphodiesterase IV Substance P Substance P Receptor Histamine Receptor Chymase CCR- 1 CC Chemokine Receptor Interleukin-2 (IL-2) Interleukin-4 (IL-4) WO 00/62736 PCT/USOO/08020 10 Interleukin-12 (IL-12) Interleukin-5 (IL-5) Interleukin-6 (IL-6) Interleukin-7 (IL-7) Interleukin-8 (IL-8) Interleukin-12 Receptor (IL-12R) Interleukin-7 Receptor (IL-7R) Interleukin- 1 (IL-i) 5 Interleukin- 14 Receptor (IL-14R) Interleukin- 14 CCR-2 CC Chemokine Receptor CCR-3 CC Chemokine Receptor CCR-4 CC Chemokine Receptor CCR-5 CC Chemokine Receptor Prostanoid Receptors GATA-3 Transcription Factor Neutrophil Adherence Receptor MAP Kinase 10 Interleukin- 15 (IL-15) Interleukin- 15 Receptor (IL-I 5R) Interleukin- 11 (IL-11) Interleukin- 11 Receptor (IL-li R) NFAT Transcription Factors STAT 4 MIP- 1 a MCP-2 MCP-3 MCP-4 15 Cyclophillin (A, B, etc.) Phospholipase A2 Basic Fibroblast Growth Factor Metalloproteinase CSBP/p38 MAP Kinase Tryptase Receptor PDG2 Interleukin-3 (IL-3) Interleukin- 10 (IL- 10) Cyclosporin A - Binding Protein 20 FK506-Binding Protein a4Pi Selectin Fibronectin a4D7 Selectin Table 1: Pulmonary Disease or Condition Pulmonary and Inflammation Targets cMad CAM-1 LFA-I (CD1 a/CD 18) PECAM-1 LFA-l Selectin 25 C3bi PSGL-i E-Selectin P-Selectin CD-34 L-Selectin p150,95 Mac- I (CD I Ib/CDi18) Fucosyl transferase VLA-4 30 STAT-i STAT-2 CD-18/CDiia CDiib/CDi8 ICAM2 and ICAM3 G~a CCR3 (Eotaxin Receptor) CCR1, CCR2, CCR4, CCR LTB-4 AP- 1 Transcription Factor 35 Protein kinase C Cysteinyl Leukotriene Receptor Tachykinnen Receptors (tach R) 16B Kinase 1 & 2 Interleukin-2 Receptor (IL-2R) (e.g., Substance P, NK-1 & NK-3 Receptors) STAT 6 c-mas NF-Interleukin-6 (NF-IL-6) Interleukin- 10 Receptor (IL-i1 OR) 40 Interieukin-3 (IL-3) Interleukin-2 Receptor (IL-2R) Interieukin-i3 (IL-M3) Interleukin-2 Receptor (IL-i2R) Interleukin- 14 (IL- 14) Interleukin-6 Receptor (IL-6R) Interleukin- 16 (IL- 16) Interleukin- 13 Receptor (IL-i1 3R) Meduliasin Interleukin-16 Receptor (IL-i6R) 45 Adenosine A, Receptor (AA R) Tryptase B P Adenosine A 2 b Receptor (A 2 ,, R) Adenosine A, Receptor (A, R) P3 Tryptase STAT-3 Adenosine A 2 a Receptor (AU, R) IgE Receptor P Subunit (IgE R 3 Fc-epsilon receptor CD23 antigen IgE Receptor a Subunit (IgE R a) 50 IgE Receptor Fc Epsilon Receptor (IgERFc R) Substance P Receptor Histidine decarboxylase Tryptase- 1 Prostaglandin D Synthase Eosinophi Cationic Protein Eosinophil Derived Neurotoxin Bosinophil Peroxidase Endothelial Nitric Oxide Synthase Endothelial Monocyte Activating Factor 55 Neutrophil Oxidase Factor Cathepsin G Macrophage Inflammnatory Protein-i- Interleukin-8 Receptor a Subunit (IL-S Ra) Apha/Rantes Receptor Endothelin Receptor ET-B WO 00/62736 PCT/USOO/08020 11 These genes, and others, are involved in the normal functioning of respiration as well as in diseases associated with respiratory pathologies, including cystic fibrosis, asthma, pulmonary hypertension and vasoconstriction, chronic obstructive pulmonary disease (COPD), pulmonary transplantation rejection, pulmonary infections, chronic bronchitis, respiratory distress syndrome 5 (ARDS), allergic rhinitis, lung cancer and lung metastatic cancers and other airway diseases, including those with inflammatory response. Anti-sense oligos to the target receptors, e. g. the adenosine A,, Ala, A 2 b, and A, receptors, CCR3 (chemokine receptors), bradykinin 2B, CAM (vascular cell adhesion molecule), and eosinophil receptors, among others, have been shown to be effective in down-regulating the expression of their 10 genes. Some of these act to alleviate the symptoms or reduce respiratory ailments and/or inflammation, for example, by "down regulation" of the adenosine A 1 , Ala, A 2 b, and/or A 3 receptors and CCR3, bradykinin 2B, VCAM (vascular cell adhesion molecule) and eosinophil receptors. These agents may be utilized by the present method alone or in conjunction with anti-sense oligos targeted to other genes to validate pathway and/or networks in which they are involved. For better results, the oligos are 15 preferably administered directly into the respiratory system, e.g., by inhalation or other means, of the experimental animal, so that they may reach the lungs without widespread systemic dissemination. This permits the use of low agent doses as compared with those administered systemically or by other generalized routes and, consequently, reduces the number and degree of undesirable side effects resulting from the agents widespread distribution in the body. The agent(s) of this invention has 20 (have) been shown to reduce the amount of receptor protein expressed by the tissue. These agents, thus, rather than merely interacting with their targets, e.g. a receptor, lower the number of target proteins that other drugs may interact with. In this manner, the present agent(s) afford(s) extremely high efficacy with low toxicity. Anti-sense oligonucleotides to the A 1 , A 2 b, A 3 , bradykinin B2, GATA 3, CAM (vascular cell adhesion molecule), eosinophil receptors, and COX-2 receptors, among others, 25 have been shown to be effective in the down-regulation of the respective receptor proteins in the cell. One novel feature of this treatment, as compared to traditional treatments for adenosine-mediated bronchoconstriction, is that administration is direct to the lungs, or in situ to other tissues, organs or systems of the body. Additionally, a receptor protein itself is reduced in amount, rather than merely interacting with a drug, and toxicity is reduced. Other proteins that may be targeted with anti-sense 30 agents for the treatment of lung conditions include, but are not limited to: CCR3 (chemokine) receptors, human Ala adenosine receptor, human A 2 adenosine receptor, human IgE receptor P, human Fc-epsilon receptor CD23 antigen, human histidine decarboxylase, human beta tryptase, human tryptase-I, human prostaglandin D synthase, human cyclooxigenase-2, human eosinophil cationic protein, human eosinophil derived neurotoxin, human eosinophil peroxidase, human intercellular 35 adhesion molecule-1 (ICAM-1), human vascular cell adhesion molecule-1 (VCAM-1), human endothelial leukocyte adhesion molecule-1 (ELAM-1), human P selectin, human endothelial monocyte activating factor, human IL-3, human IL-4, human IL-5, human IL-6, human IL-8, human monocyte derived neutrophil chemotactic factor, human neutrophil elastase, human neutrophil oxidase factor, human cathepsin G, human defensin 1, human defensin 3, human macrophage inflammatory protein- 1 40 alpha, human muscarinic acetylcholine receptor HM3, human fibronectin, human GM-CSF, human tumor necrosis factor a, human leukotriene C4 synthase, human major basic protein, and human endothelin 1. Although not intended to be exclusive, a more extensive list of genes is provided below. Some of these act to alleviate the symptoms or reduce respiratory ailments and/or inflammation, for example, by "down regulation" of the adenosine A 1 , Ala, A 2 b, and/or A, receptors and CCR3, 45 bradykinin 2B, VCAM (vascular cell adhesion molecule) and eosinophil receptors. These agents are preferably administered directly into the respiratory system, e.g., by inhalation or other means, so that they may reach the lungs without widespread systemic dissemination. This permits the use of substantially lower doses of the agent of the invention as compared with those administered by the prior art, systemically or by other generalized routes and, consequently, reduce undesirable side effects 50 resulting from the agents widespread distribution in the body. The agent(s) of this invention has WO 00/62736 PCT/USOO/08020 12 (have) been shown to reduce the amount of receptor protein expressed by the tissue. These agents, thus, rather than merely interacting with their targets, e.g. a receptor, lower the number of target proteins that other drugs may interact with. In this manner, the present agent(s) afford(s) extremely high efficacy with low toxicity. In these latter targets, and in target genes in general, it is particularly 5 imperative to eliminate or reduce the adenosine content of the corresponding anti-sense oligonucleotide to prevent their breakdown products from liberating adenosine. As used herein, the term "treat" or "treating" asthma refers to a treatment which decreases the likelihood that the subject administered such treatment will manifest symptoms of the lung disease. The term "downregulate" refers to inducing a decrease in production, secretion or availability (and thus 10 a decrease in concentration) of the targeted intracellular protein. The present invention is concerned primarily with the treatment of human subjects. However, the agents and methods disclosed here may also be employed for veterinary purposes, such as is the case in the treatment of other mammals, such as cattle, horses, wild animals, zoo animals, and domestic animals, e. g. dogs and cats. Targeted proteins are preferably mammalian and more preferably of the same species as the subject being 15 treated. In general, "anti-sense" refers to the use of small, synthetic oligonucleotides, resembling single-stranded DNA, to inhibit gene expression by inhibiting the function of the target messenger RNA (mRNA). Milligan, J. F. et al., J. Med. Chem. 36(14), 1923-1937 (1993). In the present invention, inhibition of gene expression of the A, or A, adenosine receptor is desired. Gene expression is inhibited through hybridization to coding (sense) sequences in a specific messenger RNA (mRNA) 20 target by hydrogen bonding according to Watson-Crick base pairing rules. The mechanism of anti sense inhibition is that the exogenously applied oligonucleotides decrease the mRNA and protein levels of the target gene or cause changes in the growth characteristics or shapes of the cells. Id. See, also Helene, C. and Toulme, J., Biochim. Biophys. Acta 1049, 99-125 (1990); Cohen, J. S. D., Ed., Oligodeoxynucleotides as Anti-sense Inhibitors of Gene Expression; CRC Press: Boca Raton, FL 25 (1987). As used herein, "anti-sense oligonucleotide" is defined as a short sequence of synthetic nucleotide that (1) hybridizes to any coding sequence in an mRNA which codes for the targeted protein, according to hybridization conditions described below, and (2) upon hybridization causes a decrease in gene expression of the A, or A, adenosine receptor. The receptors discussed above are mere examples of the high power of the present technology. In fact, a large number of genes may be 30 targeted in a similar manner by practicing the present methods, to significantly down-regulate or obliterate protein expression and observe any changes wrought to one or more functions within a system, e.g. the respiratory system and other lung disease associated targets. By means of example, in the respiratory system, the targets may be associated with difficulties of breathing, bronchoconstriction, inflammation, allergic rhynitis, chronic bronchitis, surfactant depletion, and 35 others associated with diseases and conditions such as chronic obstructive pulmonary disease (COPD), pulmonary transplantation rejection, pulmonary infections, inhalation bums, Acute Respiratory Distress Syndrome (ARDS), cystic fibrosis, pulmonary fibrosis, radiation pulmonitis, tonsilitis, emphysema, dental pain, oral inflammation, joint pain, esophagitis, cancers afflicting the respiratory system either directly such as lung cancer, esophageal cancer, and the like, or indirectly by means of 40 metastases, among others. These functions are of great interest because of their association with respiratory dysfunction, as is the case in asthma, allergies, allergic rhinitis, pulmonary bronchoconstriction and hypertension, chronic obstructive pulmonary disease (COPD), pulmonary transplantation rejection, pulmonary infections, allergy, asthma, cystic fibrosis (CF), Acute Respiratory Distress Syndrome (ARDS) as well as infantile and pregnancy-related RDS, cancer, etc., which either 45 directly or by metastasis afflict the lung, the present anti-sense oligonucleotides may be directed to a list of target mRNAs, which includes the targets listed in Table 1 above, among others. The oligos of this invention may be obtained by first selecting fragments of a target nucleic acid having at least 4 contiguous nucleic acids selected from the group consisting of G and C and/or having a specific type and/or extent of activity, and then obtaining a first oligonucleotide 4 to 60 50 nucleotides long which comprises the selected fragment and has a thymidine (T) nucleic acid content WO 00/62736 PCT/USOO/08020 13 of up to and including about 15%, preferably, about 12%, about 10%, about 7%, about 5%, about 3%, about 1%, and more preferably no thymidine. The latter step may be conducted by obtaining a second oligonucleotide 4 to 60 nucleotides long comprising a sequence which is anti-sense to the selected fragment, the second oligonucleotide having an adenosine base content of up to and including about 5 15%, preferably about 12%, about 10%, about 7%, about 5%, about 3%, about 1%, and more preferably no adenosine. When the selected fragment comprises at least one thymidine base, an adenosine base may be substituted in the corresponding anti-sense nucleotide fragment with a universal base selected from the group consisting of heteroaromatic bases which bind to a thymidine base but have less than about bout 10%, preferably less than about 1%, and more preferably less than about 10 0.3% of the adenosine base agonist activity at the adenosine A,, A 2 a, A 2 b and A, receptors, and heteroaromatic bases which have no activity at the adenosine A 2 a receptor, when validating in the respiratory system. Other adenosine activities in other systems may be determined in other systems, as appropriate. The analogue heteroaromatic bases may be selected from all pyrimidines and purines, which may be substituted by 0, halo, NH 2 , SH, SO, SO2, SO 3 , COOH and branched and fused primary 15 and secondary amino, alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, alkoxy, alkenoxy, acyl, cycloacyl, arylacyl, alkynoxy, cycloalkoxy, aroyl, arylthio, arylsulfoxyl, halocycloalkyl, alkylcycloalkyl, alkenylcycloalkyl, alkynylcycloalkyl, haloaryl, alkylaryl, alkenylaryl, alkynylaryl, arylalkyl, arylalkenyl, arylalkynyl, arylcycloalkyl, which may be further substituted by 0, halo, NH 2 , primary, secondary and tertiary amine, SH, SO, SO 2 , SO 3 , cycloalkyl, heterocycloalkyl and 20 heteroaryl. The pyrimidines and purines may be substituted at all positions as is known in the art, but preferred are those which are substituted at positions 1, 2, 3, 4, 7 and/or 8. More preferred are pyrimidines and purines such as theophylline, caffeine, dyphylline, etophylline, acephylline piperazine, bamifylline, enprofylline and xantine having the chemical formula 0 M I I I || a wherein R' and R 2 are independently H, alkyl, alkenyl or alkynyl and R 3 is H, aryl, dicycloalkyl, 25 dicycloalkenyl, dicycloalkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, 0-cycloalkyl, 0-cycloalkenyl, 0-cycloalkynyl, NH 2 -alkylamino-ketoxyalkyloxy-aryl, mono and dialkylaminoalkyl-N-alkylamino

SO

2 aryl, among others. Similar modifications in the sugar are also embodiments of this invention. Reduced adenosine content of the anti-sense oligos corresponding to the thymidines (T) present in the target RNA serves to prevent the breakdown of the oligos into products that free adenosine into thd 30 system, e.g. the lung, brain, heart, kidney, etc., tissue environment and, thereby, to prevent any unwanted effects due to it. By means of example, the Nf6B transcription factor may be selected as a target, and its mRNA or DNA searched for low thymidine (T) or desthymidine (desT) fragments. Only desT segments of the mRNA or DNA are selected which, in turn, will produce desA anti-sense as their complementary strand. When a number of RNA desT segments are found, the sequence of the anti 35 sense segments may be deduced. Typically, about 10 to 30 and even larger numbers of desA anti-sense sequences may be obtained. These anti-sense sequences may include some or all desA anti-sense oligonucleotide sequences corresponding to desT segments of the mRNA of the target, such as anyone of those shown in Table 1 above, in Table 2 below, and others associated with functions of the brain, cardiovascular and renal systems, and many others. When this occurs, the anti-sense oligonucleotides 40 found are said to be 100% A-free. For each of the original desA anti-sense oligonucleotide sequences corresponding to the target gene, e.g. the NF6B transcription factor, typically about 10 to 30 sequences may be found within the target gene or RNA which have a low content of thymidine (RNA). In accordance with this invention, the selected fragment sequences may also contain a small number of thymidine (RNA) nucleotides within the secondary or tertiary or quaternary sequences. In some cases, WO 00/62736 PCT/USOO/08020 14 a large adenosine content may suffice to render the anti-sense oligonucleotide less active or even inactive against the target. In accordance with this invention, these so called "non-fully desA" sequences may preferably have a content of adenosine of less than about 15%, about 12%, about 10%, about 7%, about 5%, and about 2% adenosine. Most preferred is no adenosine content (0%). In some 5 instances, however, a higher content of adenosine is acceptable and the oligonucleotides still fail to show detrimental "adenosine activity". A particular important embodiment is that where the adenosine nucleotide is "fixed" or replaced by a "Universal or alternative" base that may base-pair with similar or equal affinity to two or more of the four nucleotide present in natural DNA: A, G, C, and T. A universal or alternative base is defined in this patent as any compound, more commonly an 10 adenosine analogue, which has substantial capacity to hybridize to thymidine, while at the same time having reduced, or substantially lacking, ability to bind adenosine receptors or other molecules through which adenosine may exert an undesirable side effect in the experimental animal or in a cell system. Alternatively, adenosine analogs which completely fail to activate, or have significantly reduce ability for activating, adenosine receptors, such as the adenosine A,, A 2 , and/or A, receptors, most preferably 15 A, receptors, and those that may even act as agonists of the adenosine Aa, receptor, may be used. One example of a universal base is a-deoxyribofuranosol-(5-nitroindole), and an artisan will know how to select others. This "fixing" step generates further novel sequences, different from those anti-sense to the ones found in nature, that permits the anti-sense oligonucleotide to bind, preferably equally well, with the target RNA. Other examples of universal or alternative bases are 2-deoxyribosyl-(5 20 nitroindole). Other examples of universal bases are 3 - nitropyrrole - 2' - deoxynucleoside, 5 - nitro indole, 2 - deoxyribosyl - (5 - nitroindole), 2-deoxyribofuranosyl - (5-nitroindole), 2' - deoxyinosine, 2' -deoxynebularine, 6H, 8H-3,4-dihydropyrimido [ 4, 5 - c] oxazine - 7 - one and 2 - amino - 6 -methoxy aminopurine. In addition to the above, Universal bases which may be substituted for any other base although with somewhat reduced hybridization potential, include 3 - nitropyrrole 2' - deoxynucleoside 25 2 - deoxyribofuranosyl - (5 - nitroindole), 2' - deoxyinosine and 2' - deoxynebularine (Glen Research, Sterling, VA). More specific mismatch repairs may be made using "P" nucleotide, 6H, 8H - 3, 4 dihydropyrimido [4,5 - c] [1, 2] oxazin - 7 - one, which base pairs with either guanine (G) or adenine (A) and "K" nucleotide, 2 - amino - 6 - methoxyaminopurine, which base pairs with either cytidine (C) or thymidine (T), among others. Others which are known in the art or will become available are also 30 suitable. See, for example, Loakes, D. and Brown, D. M., Nucl. Acids Res. 22:4039-4043 (1994); Ohtsuka, E. et al., J. Biol. Chem.260(5):2605-2608 (1985); Lin, P.K.T. and Brown, D. M., Nucleic Acids Res. 20(19):5149-5152 (1992; Nichols, R. et al., Nature 369(6480): 492-493 (1994); Rahmon , M. S. and Humayun, N. Z., Mutation Research 377 (2): 263-8 (1997); Amosova, 0., et al., Nucleic Acids Res. 25 (!0): 1930-1934 (1997); Loakes D. & Brown, D. M., Nucleic Acids Res. 22 (20): 4039 35 4043 (1994), the entire sections relating to universal bases and their preparation and use in nucleic acid binding being incorporated herein by reference. When non-fully desT sequences are found in the naturally occurring target, they typically are selected so that about 1 to 3 universal base substitutions will suffice to obtain a 100% "desA" anti-sense oligonucleotide. Thus, the present method provides either anti-sense oligonucleotides to different targets which are low in, or devoid of, A content, as well 40 as anti-sense oligonucleotides where one or more adenosine nucleotides, e. g. about 1 to 3, or more, may be "fixed" by replacement with a "Universal" or "replacement" base. Universal bases are known in the art and need not be listed herein. An artisan will know which bases may act as universal bases, and replace them for A. Table 2 below provides a selected number of targets to which the agents of the invention are effectively applied. Others, however, may also be targeted. 45 Table 2: Cancer Targets Transforming Therapy Onco2enes Targets ras thymidylate synthetase src thymidylate synthetase 50 myc dihydrofolate reductase WO 00/62736 PCT/USOO/08020 15 bcl-2 thymidine kinase deoxycytidine kinase ribonucleotide reductase Angiogenesis factors Adhesion Molecules 5 Oncogenes Folate Pathway Enzymes DNA repair genes (One Carbon Pool) Telomerase HMG CoA Reductase Farnesyl Transferase 10 Glucose-6-Phosphate Transferase A group of preferred targets for the treatment of cancer are genes associated with any of different types of cancers, or those generally known to be associated with malignancies, whether they are regulatory or involved in the production of RNA and/or proteins. Examples are transforming oncogenes, including, but not limited to, ras, src, myc, and BCL-2, among others. Other targets are 15 those to which present cancer chemotherapeutic agents are directed to, such as various enzymes, primarily, although not exclusively, thymidylate synthetase, dihydrofolate reductase, thymidine kinase, deoxycytidine kinase, ribonucleotide reductase, and the like. The present technology is particularly useful in the treatment of cancer ailments given that traditional cancer therapies are fraught with the unresolved problem of selectively killing cancer cells while preserving normal living cells from the 20 devastating effects of treatments such as chemotherapy, radiotherapy, and the like. The present technology provides the ability of selectively attenuating or enhancing a desired pathway or target. This approach provides a significant advantage over standard treatments of cancer because it permits the selection of a pathway, including primary, secondary and possibly tertiary targets, which are not generally expressed simultaneously in normal cells. Thus, the present agent may be administered to a 25 subject to cause a selective increase in toxicity within tumor cells that, for instance, express all three targets while normal cells that may expresses only one or two of the targets will be significantly less affected or even spared. A group of preferred targets for the treatment of cancers are genes associated with different types of cancers, or those generally known to be associated with malignancies, whether they are regulatory or involved in the production of RNA and/or proteins. Examples are transforming 30 oncogenes, including, but not limited to, ras, src, myc, and BCL-2, among others. Other targets are those to which present cancer chemotherapeutic agents are directed to, such as various enzymes, primarily, although not exclusively, thymidylate synthetase, dihydrofolate reductase, thymidine kinase, deoxycytidine kinase, ribonucleotide reductase, and the like. In one embodiment, at least one of the mRNAs to which the oligo of the invention is targeted 35 encodes a protein such as transcription factors, stimulating and activating factors, intracellular and extracellular receptors and peptide transmitters in general, interleukins, interleukin receptors, chemokines, chemokine receptors, endogenously produced specific and non-specific enzymes, immunoglobulins, antibody receptors, central nervous system (CNS) and peripheral nervous and non nervous system receptors, CNS and peripheral nervous and non-nervous system peptide transmitters, 40 adhesion molecules, defensines, growth factors, vasoactive peptides and receptors, and binding proteins, among others; or the mRNA is corresponding to an oncogene and other genes associated with various diseases or conditions. Examples of target proteins are eotaxin, major basic protein, preproendothelin, eosinophil cationic protein, P-selectin, STAT 4, MIP-la, MCP-2, MCP-3, MCP-4, STAT 6, c-mas, NF-IL-6, cyclophillins, PDG2, cyclosporin A-binding protein, FK5-binding protein, 45 fibronectin, LFA-1 (CDlla/CD18), PECAM-1, C3bi, PSGL-1,CD-34, substance P, p150,95, Mac-1 (CD1lb/CD18), VLA-4, CD-18/CD1la, CD1lb/CD18, C5a, CCR1, CCR2, CCR4, CCR5, and LTB-4, among others. Others are, however, suitable, as well. In another embodiment, at least one of the mRNAs to which the oligo is targeted encodes intracellular and extracellular receptors and peptide transmitters such as sympathomimetic receptors, parasympathetic receptors, GABA receptors, 50 adenosine receptors, bradykinin receptors, insulin receptors, glucagon receptors, prostaglandin receptors, thyroid receptors, androgen receptors, anabolic receptors, estrogen receptors, progesterone WO 00/62736 PCT/USOO/08020 16 receptors, receptors associated with the coagulation cascade, adenohypophyseal receptors, adenohypophyseal peptide transmitters, and histamine receptors (HisR), among others. However others are also contemplated. The encoded sympathomimetic receptors and parasympathomimetic receptors include acetylcholinesterase receptors (AcChaseR) acetylcholine receptors (AcChR), atropine 5 receptors, muscarinic receptors, epinephrine receptors (EpiR), dopamine receptors (DOPAR), and norepinephrine receptors (NEpiR), among others. Further examples of encoded receptors are adenosine A, receptor, adenosine A 2 B receptor, adenosine A, receptor, endothelin receptor A, endothelin receptor B, IgE high affinity receptor, muscarinic acetylcholine receptors, substance P receptor, histamine receptor, CCR-1 CC chemokine receptor, CCR-2 CC chemokine receptor, CCR-3 CC chemokine 10 receptor (Eotaxin Receptor), interleukin-1 receptor (IL-i R), interleukin-1 receptor (IL-1R), interleukin-1 receptor (IL-ipR), interleukin-3 receptor (IL-3R), CCR-4 CC chemokine receptor, cysteinyl leukotriene receptors, prostanoid receptors, GATA-3 transcription factor receptor, interleukin-1 receptor (IL-iR), interleukin-4 receptor (IL-4R), interleukin-5 receptor (IL-5R), interleukin-8 receptor (IL-8R), interleukin-9 receptor (IL-9R), interleukin-11 receptor (IL-11R), 15 bradykinin B2 receptor, sympathomimetic receptors, parasympathomimetic receptors, GABA receptors, adenosine receptors, bradykinin receptors, insulin receptors, glucagon receptors, prostaglandin receptors, thyroid receptors, androgen receptors, anabolic receptors, estrogen receptors, progesterone receptors, receptors associated with the coagulation cascade, adenohypophyseal receptors, and histamine receptors (HisR). Others are also contemplated even though not listed herein. 20 The encoded enzymes for development of the oligos of the invention include synthetases, kinases, oxidases, phosphatases, reductases, polysaccharide, triglyceride, and protein hydrolases, esterases, elastases, and , polysaccharide, triglyceride, lipid, and protein synthases, among others. Examples of target enzymes are tryptase, inducible nitric oxide synthase, cyclooxygenase (Cox), MAP kinase, eosinophil peroxidase, p2-adrenergic receptor kinase, leukotriene c-4 synthase, 5-lipooxygenase, 25 phosphodiesterase IV, metalloproteinase, tryptase, CSBP/p38 MAP kinase, neutrophil elastase, phospholipase A 2 , cyclooxygenase 2 (Cox-2), fucosyl transferase, chymase, protein kinase C, thymidylate synthetase, dihydrofolate reductase, thymidine kinase, deoxycytidine kinase, and ribonucleotide reductase, among others. Any enzyme associated with a disease or condition, however, is suitable as a target for this invention. Suitable encoded factors for application of this invention are, 30 among others, Nf6B transcription factor, granulocyte macrophage colony stimulating factor (GM CSF), AP-1 transcription factor, GATA-3 transcription factor, monocyte activating factor, neutrophil chemotactic factor, granulocyte/macrophage colony-stimulating-factor (G-CSF), NFAT transcription factors, platelet activating factor, tumor necrosis factor a (TNF a), and basic fibroblast growth factor (BFGF). Additional factors are also within the invention even though not specifically mentioned. 35 Suitable adhesion molecules for use with this invention include intracellular adhesion molecules 1 (ICAM-1), 2 (ICAM-2) and 3 (ICAM-3), vascular cellular adhesion molecule (VCAM), endothelial leukocyte adhesion molecule-1 (ELAM-1), neutrophil adherence receptor, mad CAM-1, and the like. Other known and unknown factors (at this time) may also be targeted herein. Among the cytokines, lymphokines and chemokines preferred are interleukin-1 (IL-1), interleukin-1p (IL-1 ), interleukin-3 40 (IL-3), interleukin-4 (IL-4), interleukin-5 (IL-5), interleukin-8 (IL-8), interleukin-9 (IL-9), interleukin II (IL-1 1),CCR-5 CC chemokine, and Rantes. Others, however, may also be targeted, as they are known to be involved in specific diseases or conditions to be treated, or for their generic activities, such as inflammation. Examples of defensins for the practice of this invention are defensin 1, defensin 2, and defensin 3, and of selectins are a4pl selectin, a4P7 selectin, LFA-1 selectin, E-selectin, P 45 selectin, and L-selectin. Examples of oncogenes, although not an all inclusive list, are ras, src, myc, and bcBCL. Others, however, are also suitable for use with this invention. The agents administered in accordance with this invention are preferably designed to be anti sense to target genes and/or mRNAs related in origin to the species to which it is to be administered. When treating humans, the agents are preferably designed to be anti-sense to a human gene or RNA. 50 The agents of the invention encompass oligonucleotides which are anti-sense to naturally occurring WO 00/62736 PCT/USOO/08020 17 DNA and/or RNA sequences, fragments thereof of up to a length of one (1) base less than the targeted sequence, preferably at least about 7 nucleotides long, oligos having only over about 0.02%, more preferably over about 0.1%, still more preferably over about 1%, and even more preferably over about 4% adenosine nucleotides, and up to about 30%, more preferably up to about 15%, still more 5 preferably up to about 10% and even more preferably up to about 5%, adenosine nucleotide, or lacking adenosine altogether, and oligos in which one or more of the adenosine nucleotides have been replaced with so-called universal bases, which may pair up with thymidine nucleotides but fail to substantially trigger adenosine receptor activity. Examples of human sequences and fragments, which are not limiting, of anti-sense oligonucleotide of the invention are the following fragments as well as shorter 10 segments of the fragments and of the full gene or mRNA coding sequences, exons and intron-exon junctions encompassing preferably 7, 10, 15, 18 to 21, 24, 27, 30, n-1 nucleotides for each sequence, where n is the sequence=s total number of nucleotides. These fragments may be selected from any portion of the longer oligo, for example, from the middle, 5'- end, 3'- end or starting at any other site of the original sequence. Of particular importance are fragments of low adenosine nucleotide content, that 15 is, those fragments containing less than or about 30%, preferably less than or about 15%, more preferably less than or about 10%, and even more preferably less than or about 5%, and most preferably those devoid of adenosine nucleotide, either by choice or by replacement with a universal base in accordance with this invention. The agent of the invention includes as a most preferred group sequences and their fragments where one or more adenosines present in the sequence have been 20 replaced by a universal base (B), as exemplified here. Similarly, also encompassed are all shorter fragments of the B-containing fragments designed by substitution of B(s) for adenosine(s) (A(s)) contained in the sequences, fragments thereof or segments thereof, as described above. A limited list of sequences and fragments is provided below. Some of the examples of anti-sense oligonucleotide sequence fragments target the initiation 25 codon of the respective gene, and in some cases adenosine is substituted with a universal or alternative base adenosine analogue denoted as "B", which lacks ability to bind to the adenosine A, and/or A, receptors. In fact, such replacement nucleotide acts as a "spacer". Many of the examples shown below provide one such sequence and many fragments overlapping the initiation codon, preferably wherein the number of nucleotides n is about 7, about 10, about 12, about 15, about 18, about 21 and up to 30 about 28, about 35, about 40, about 50, about 60. Human Receptor-related Antisense Polynucleotide 5'-GGCGGCCTGG AAAGCTGAGA TGGAGGGCGG CATGGCGGGC ACAGGCTGGG C TGCTTTTCT TTTCTGGGCC TCTGTGGTCT GTTTITCT GGCCCTGCTG GGGCGCTCTC CGCCGCCCGC CTGGCTCCCG GBGCCCBTGB TGGGCBTGCC GTGGTTCTTG CCCTCCTTTG GCTGCCGTGC CCGCTCCCCG GCCTCCTGGC GGGTGGCCGT 35 TGGGCCCGTG TTCCCCTGGG GCCTGGGGCT CCCTTCTCTC GCCCTTCTTG CTGGGCCTCT GCTGCTGCTG GTGCTGTGGC CCCCGTACA CCGAGGAGCC CATGATGGGC ATGCCACAGA CGACAGGCGT BCBCCGBGGB GCCCBTGBTG GGCBTGCCBC BGBCGBCBGG C GGC GCC GTG CCG CGT CTT GGT GGC GGC GG GTT CGC GCC CGC GCG GGG CCC CTC CGG TCC GTT CGC GCC CGC GCG GGG CCC CTC CGG TCC CGG GTC GGG GCC CCC CGC GGC C GCC TCG GGG CTG GGG CGC TGG TGG CCG GG CCG CGC CTC CGC CTG CCG CTT CTG GCT 40 GGG CCC CGG GCG CCC CCT CCC CTC TTG CTC GGG TCC CCG TG ACA GCG CGT CCT GTG TCT CCA GCA GCA TGG CCG GGC CAG CTG GGC CCC BCB GCG CGT CCT GTG TCT CCB GCB GCB TGG CCG GGC CBG CTG GGC CCC ACA GAG CAG TGC TGT TGT TGG GCA TCT TGC CTT CCC AGG G BCB GBG CB TGC TGT TGT TGG GCB TCT TGC CTT CCC BGG GCC CTT TTC TGG TGG GGT GGT GCT GTT GTT GGG CTT TCT TCT GTT CCC BCB GBG CBG TGC TGT TGT TGG GCB TCT TGC CTT CCC BGG GCC CTT TTC TGG TGG GGT GGT GCT GTT 45 GTT GGG C TTT CTT CTG TTC CC TTT CCC CTG GGT CIT CC CTC CTG CTC TTT TTT C ATT TGC TCT CCT ATT ACT TTC TGT GTC CAT TTT TTC ATT AAC CGA GCT GT BTT TGC TCT CCT BTT BCT TTC TGT GTC CBT TTT TTC BTT BBC CGB GCT GT GCC TGT GTC TGT CCT CCT GCT TCG TTC CTC TCG TTC CTG CTT GGT GCC CTT GCC G GTC CTG CTC CTC CGG GCT GTG G GTC GTG GCC CTG GCT CCG GCT GGT GGG CTC CCC TGG CCT TCG CTG GCT GGC GGC GTG C GGG TCT TGC TCT GGG CCT GGC TGT GGC CGT GGT TGG GGG TCT 50 TC GCT GCC TCC GTT TGG GTG GC TCT CTG AAT ATT GAC CTT CCT CCA TGG CGG TCC TGC TTG GAT TCT CCC GA TCT CTG BBT BTT GBC CTT CCT CCB TGG CGG TCC TGC TTG GBT TCT CCC GB GCC TTT CCT GGT TCT CTT GTT GTT TTT GGG GTT TGG CTT ACA GTA GAG TAG GGG ATT CCA TGG CAG GAG CCA TCT WO 00/62736 PCT/USOO/08020 18 TCT TCA TGG ACT CC TTC AAG GAG ACC TTA GGT TTC TGA GGG ACT GCT AAC ACG CCA TCT GGA GC BCB GTB GBG TBG GGG BTT CCB TGG CBG GBG CCB TCT TCT TCB TGG BCT CC TTC BBG GBG BCC TTB GGT TTC TGB GGG BCT GCT BBC BCG CCB TCT GGB GC GTT GTT TTT GGG GTT TGG CTT GCC TTT CCT GGT TCT CTT BCB GTB GBG TBG GGG BTT CCB TGG CBG GBG CCB TCT TCT TCB TGG BCT CC TTC BBG 5 GBG BCC TTB GGT TTC TGB GGG BCT GCT BBC BCG CCB TCT GGB GC GCC TGT GTC TGT CCT CCT GCT TCG TTC CTC TCG TTC CTG CTT GGT GCC CTT GCC G GTC CTG CTC CTC CGG GCT GTG G GTC CTC GCC CTG GCT CCG GCT GGT GGG CTC CCC TGG CCT TCG CTG GCT GGC GGC GTG C CCC BGB BCG BGB CCC GGB CCG BCB GGC CGT GGT TGG GGG TCT TC GCT GCC TCC GTT TGG GTG GC GAT CTC TGA ATA TTGA CCT TCC ATG GCG GTC CTG CTT GGA GBT CTC TGB BTB TTGB CCT TCC BTG GCG GTC CTG CTT GGB TCT 10 GGG GTG TCC TGG CCT TCG TGG TTC CTC TTC CTT CGT TTG CCG TCC GCG GGG GCC CCC GGG CCT GGC TGC GCT CCT GCC CCG CCT CTT TCC CGG GCT CTT GCG CTG GGG GGT GCT CC CGT GTG TTT GCG CCC TC CTC CTG GTC GCG CTT GTC GTT TTG GGG CCG GCT TTG CCC GCC TCC CGG CGC CTG GCC CGG CC TTC CTG GGC TGC GTG CGC GTT CTG TTC TTC TTC CTG GCT CTG GGG TGT CCT GGC CTU CGT GGT TCC TCT TCC TTC GTT TGC CGT CCG CGG GGG CCC CCG GGC CT GGC TGC GCT CCT GCC CCG CCT CTT TCC CGG 15 GCT CTT GCG CTG GGG GGT GCT CCC GTG TGT TTG CGC CCT CCT CCT GGT CGC GCT TGT CGT TTT GG GGC CGG CTT TGC CCG CCT CCC GGC GCC TGG CCC GGC CTT CCT GGG CTG CGT GCG CGT TCT GTT CTT CTT CCT GGC GCA GGA GAC AGG GCA GGG CGA TCA GGA GCA GCG TGA GCC AAA GGA GGA CCA TCG GGA ACG CAG CTC CGG AAC GCA GGA CAG AGG TGC C GC BGG BGB CBG GGC BGG GCG BTC BGG BGC BGC GTG BGC CBB BGG BGG BCC BTC GGG BBC GCB GCT CCG GBB CGC BGG BCB GBG GTG CC TCT GCC 20 CTG TCC GCC GGC TCT TCG GTG GCT CGG CCC CGC TCC TTG TCT TGC CGC GGG TTG GTT CCT GGG CCT GGT TCT TGC GGG CGT TTC GGT CTG CTG GCT GGT CTG GGC CCG CGG TGC GGC GGG TGG CTT GCT GTT CTG CCT GGG CTC TCC CCT CTC CTC CTT TTC TCC CTT CCT CTG TCT TGC CTC CTU CCT CTG GGT CCT CTT GGC CTG GGC GCT CTT CCC CTC GGG CGG CTG CGG GCG CTC GTG CTG CCT GGT CCG CTC CCT GGG GGT GCT CCT TCC CTT TCC CCG CTC GTG GGG TTT GCG GGG CTG GGC TGC CCT GGG GGG TCT GGG CCT 25 TTT GGG GTC GGC TGG CTG CTG CTT CGG GCC GCC TGG GCT TCC CTG TGC CCC TTT CCT CTG CTG GGT CCC CCT CCC GTT CCA AGC TGC ACC GCA CAG ACC GGC GCT ACA GGA CAG AGC CAG GCA AGC ACC CAT GGG GAT CCA GGC CCA GCT GTT CCB BGC TGC BCC GCB CBG BCC GGC GCT BCB GGB CBG BGC CBG GCB BGC BCC CBT GGG GBT CCB GGC CCB GCT G CTCAGTGGCC CCCAAAAGGA TGAGTAATAC ATGCGCCACG ATGATCATAT CCTTTTTACT ATGAGGCCGT GTCTGTCGTG TCTTTCCTTT GCTCTTGGTG 30 TGTCTTTGCT GTGCCCTGCC TCTCTGCCCG TGTCTGTCGT GTCTTTCCTT TGCTCTTGGT GTGTCTTTGC TGTGCCCTGC CTCTCTGCC CGTGTCTGTC GTGTCTTTCC TTTGCTCTTG GTGTGTCTTT GCTGTGCCCT GCCTCTCTGC GGGGGTGGCT TCCTGCCGCG TCTCTGGGCC GTCCCGTCCC TCGGCCCCGC GCCGCGCTCG GCTCCTCTCC CTCTGGCCCG GCTCGGGGCG GGGCGGGGCG GTGGGCGGGC GGCGCTGCCC TGCGCGCGGC GCTGGCCCCT GCTGGCCGTC GGCTGCGCGC TGCTGGCTGC CCTGCTGGCC GCGCCGGGGC CTGTCCGCCT 35 CTGCGGGCGC TGTCTCCTGG CTTGTCTCC GGCTCTTCTG CTGGGGTGGG GCTGGGCGGC CGGCCCGGTG CTGGGGCTCC TCGGGGGGGG GGGCTCTTCC GGGCTGTCTC CCTCCGGGGC GGGGGTTTCT GGCCGTGGGG GTCTTGCCTG GCCTCCGGGC TCCTGCTUGT CTTGCCTTCC TTCTCTGGTC GGTTGTGGCT CGGGGCTCCG TGGGTCCCTG GCGCCCGTTT GTGTTTTGTC TTTTCCCCTG GCGTCCCTGT GCCCCTCTCC TCTCCTTCCT CTGCTCTCG CTCTCCTTrG TGGGGCCCTC CCTGCTGCTC TTGGTTTTGG GCTTTTTTC TCTCCTCCT 40 TTTTCGTGCG TGGGCCTCC GCACGCCTCT TGCCACCTCC TGCGCAGGGC AGCGCCTTGG GGCCAGCGCC GCTCCCGGCG CGGCCAGCAG GGCAGCCAGC AGCGCGCAGC CGACGGCCAG CATGCTTCCT CCTCGGCTAC CACTCCATGG TCCCGCAGAG GCGGACAGGC GCBCGCCTC TTGCCBCCTC CTGCGCBGGG CBGCGCCTTG GGGCCBGCGC CGCTCCCGGC GCGGCCBGCB GGGCBGCCBG CBGCGCGCBG CCGBCGGCCB GCBTGCTTCC TCCTCGGCTB CCBCTCCBTG GTCCCGCBGB GGCGGBCBGG C GCTGCCCGGC GGGGTGTGCG CTTGGCGCTC 45 CCGTGCTCGG TTCTCTGTCT CCCGGTCCCC CTGCCTGGC GTCTCGGGCC TTCGTCCTCT TCCTCTTCTT CCTCCGCTC CGTGGGGGCT GCTTGGTGGG GGCCTGTGCCT CGGGGTCCCG GGGCTTCTGG CCCTTGCCGT TCATGGTGGC TAGGTGGGGC GTTCBTGGTG GCTBGGTGGG GC GGG GTG GGT BGG CCG TGT CTG GGGGTT GGC CBT GTT GGT TGC CTCT TGG TGG TGC GCC GGG CGCG TCT TGG CTT TCT TCT CCT TCG GGC CCT CGG GCC GGT GCT TGT GGGCT CCT CCC GGG CGG CCT CCC CGG GCG GGG GCT TCT TGGCG CTG GCG 50 GGG GGG CCT CCTGCT CTG TGG CTG GGC GTT CCT TGG TGT TCT GGG TGGTGG CGG GCG TGG TGG CCT CTG TGGGGG CCC GCG GCT GCB GGG GTTG CCT GTC TGC TTC GTCCTU TGC GCT CCC GGG CCG CCGGG GTG GGT AGG CCG TGT CTG GGGGTT GGC CAT GTT GGT TGC CGGG CCC GCG GCT GCA GGG G ACAGGGGCTG TAATCTTCATC TGCAGGTGGC ATGCCAGTGA AATTTAGATC ATCAAAATCC CACATCTGTG GATCTGTAAT ATTTGACATG TCCTCTCAG TTTCAGCAAT GGTTTGATCT AACTGAAGCA CCGGCCAGGB 55 CBGGGGCTGT BBTCTTCBTC TGCBGGTGGC BTGCCBGTGB BBTTTBGBTC BTCBBBBTCC CBCBTCTGTG GBTCTGTBBT BTTTGBCBTG TCCTCTTCBG TTTCBGCBB TGGTTTGBTC TBBCTGBBGC BCCGGCCBGG WO 00/62736 PCT/USOO/08020 19 TGGCTCGGTG CTTCTGCCCC TGTTGTTGCG GCGCTCGGTT GGTGTGGCCC CTGTGGTGCT TCGTTTCCCC CTCTTTCTCT TTGTTCGGGG GTTCTTGTGG CGGGCTGCTT GTCTCGTTCC GCCCTGTCGG GCGGGAAGCC TCTCTCCTCT CCCCAGATC CGCGACAGGC CGCAGGCAAG AACCAGCGCA ACCAGGGCGC GTCCGCACAG ACTTGGAGGC GGCTGCATGC TGCTACCTGC TCCAGAAGCG TCCGGTGGCC GCCGCGCC CTGTCGGGCG 5 GGBBGCCTCT CTCCTCTCCC CBGBTCCGCG BCBGGCCGCB GGCBBGBBCC BGCGCBBCCB GGGCGCGTCC GCBCBGBCTT GGBGGCGGCT GCBTGCTGCT BCCTGCTCGGGCG GGBBGCCTCCG GTGGCCGCCG CGCGTCCGGT GGCCGCCGCG CCTCTCTCCT CTCCCCGTGG CCCTGTCGGG CGGGTCCTGC CGTCCTGTCT CCTTTCTTT TGCTGTCTTG TCTTCCCGTC TCTGCTTT GTCTGTCCTC CCCGTCTCCT CCCACTGCTT CTCCCGGGGG CTTCCCCGGC TTCGGGTGGC CGGTGTCCCG GGCTCCGGCG CGGCGGCGGC TTCGGCTGCG 10 GGTGGGTGGC GCGGGCTGCC GGGTCCGCGC GGCGCCTGGG CCCTTGTGCT GCTTTGCT TGTTCCGTTC TGGCTGCTCC GGTCTGTGTT GTGGTTGTTT TGTTTCTTCT TGGGTGTGGG CCTTGCGGTT TTGGCTGTGG GCCCTTTGGG GCCTTGGCTT CTGGCTCGTC TGTCCTCCCC GTCTCCTCCC ACTGCTTCT CCCGGGGGCT TCCCCGGCTT CGGGTGGCCG GTGTCCCGGG CTCCGGCGCG GCGGCGGCTT CGGCTGCGGG TGGGTGGCGC GGGCTGCCGG GTCCGCGCGG CGCCTGGGCC CTTGTGCTGC TTTTTGCTTG TTCCGTTCTG GCTGCTCCGG 15 TCTGTGTTGT GGTTGTTTTG TTTCTrCTTG GGTGTGGGCC TTGCGGTT GGCTGTGGGC CCTTTGGGGC CTTGGCTTCT GGCTCCAT CCACATGATT GCTTAGATTT GTGCTGTATC TCTCAGGATT ATCACTGATT ACACATCCAA CCAGTGCCAG CCAAAAGGAT GCCCTGAGGC AAAGGGTTTC CATCTTGAGG CAAATTTGAG GACBTCCBC BTGBTTGCTT BGBTTTGTGC TGTBTCTCTC BGGBTTBTCB CTGBTTBCBC BTCCBBCCBG TGCCBGCCBB BBGGBTGCCC TGBGGCBBBG GGTTTCCBTC TTGBGGCBBB TTGBGGBGGGCTBBGBT 20 GBTCCBCBTC BCTBCCBCGT TGCCCBCCBC BGBGGTCBCC BCBBTGBCCG TGTBGGCBGC TGCCCBBBGG BCBBTTTGCC BGGCTGGTTG CBCGBBCTGB TTGGGTTCCG BGGTGTTBGT GGBGBTGTTT GGGGBGBGGT CTGBGTCCBC CGGGBGGBCG TTBTCCBTTT CGBBGCTBGG CGGTBBBGCC CTBCTBTCTG TBCBCBBCCC CCCTCTGCBG CBGBGTCCTG TCGTGGCGCC TGGGGCTCBG GGTCCGGGC TAAGATGATC CACATCACTA CCACGTTGCC CACCACAGAG GTCACCACAA TGACCGTGTA GGCAGCTGCC CAAAGGACAA TTTGCCAGGC 25 TGGTTGCACG AACTGATTGG GTTCCGAGGT GTTAGTGGAG ATGTTTGGGG AGAGGTCTGA GTCCACCGGG AGGACGTTAT CCATTTCGAA GCTAGGCGGT AAAGCCCTAC TATCTGTACA CAACCCCCCT CTGCAGCAGA GTCCTGTCGT GGCGCCTGGG GCTCAGGGTC CGTCCTGTCG TGGCGCCTGG GGCTCTTCTT TTGTGGGCTC TTTGGTGGCT GTGGCTGTGG TCTCTGTGGT TGCTGCCCTG GGTCTGGGGG TGTGGCCTTG GGGCCGTCCT CTGGCTCCTC CTCGTGGGCC CCC GGTGBCBTTG BGCBTGTCGG CGCGGTCCCG TTBBGBGTGG GCCCGCCAGC 30 CCAGCCACTC CACTTGGGGG CGGGTGGCCA GCACGAACAG CACCCAGAGG AAGGGGGGCG GCCCAGAAGG GCAGCCCGCA GGCCAGGATC AGGTCTGCTG CGGCCGGAGA TAATGGCATT CACCACGCGG CGGCCCAGCG CACGCCGCGC ATCCGGCCCG GGTTCTGACC TGCAGCCCCC GTCTCCTTGG CATTCCTGGG CCCCAGTCAC TCCTCTCCCT GCCCCCCTTG CTGGGGCAGG GACGGGGTG BCBTTGBGCB TGTCGGCGCG GTCCCGTTBB GBGTGGGCCC GCCAGCCCAG CCACTCCACT TGGGGGCGGG TGGCCAGCAC GAACAGCACC CAGAGGAAGG 35 GGGGCGGCCC AGAAGGGCAG CCCGCAGGCC AGGATCAGGT CTGCTGCGGC CGGAGATAAT GGCATTCACC ACGCGGCGGC CCAGCGCACG CCGCGCATCC GGCCCGGGTT CTGACCTGCA GCCCCCGTCT CCTTGGCATT CCTGGGCCCC AGTCACTCCT CTCCCTGCCC CCCTTGCTGG GGCAGGGACG GCCGTGTTGT CBGTGGTGCT GCCCGTTTGB GGTBTGGCGC TCCBCCBBTT CCCTTTTCTC CTTGTTTTCC GTTTCTCTTG CCGTCTGTGG TT ATGCCGCCCT CCATCTCAGC TTTCCAGGCC GCCTACATCG GCATCGAGGT GCTCATCGCC CTGGTCTCTG 40 TGCCCGGGAA CGTGCTGGTG ATCTGGGCGG TGAAGGTGAA CCAGGCGCTG CGGGATGCCA CCTTCTGCTT CATCGTCTCG CTGGCGGTGG CTGATGTGGC CGTGGGTGCC CTGGTCATCC CCCTCGCCAT CCTCATCAAC ATTGGGCCAC AGACCTACTT CCACACCTGC CTCATGGTTG CCTGTCCGGT CCTCATCCTC ACCCAGAGCT CCATCCTGGC CCTGCTGGCA ATTGCTGTGG ACCGCTACCT CCGGGTCAAG ATCCCTCTCC GGTACAAGAT GGTGGTGACC CCCCGGAGGG CGGCGGTGGC CATAGCCGGC TGCTGGATCC TCTCCTTCGT GGTGGGACTG 45 CCCCTATGT TTGGCTGGAA CAATCTGAGT GCGGTGGAGC GGGCCTGGGC AGCCAACGGC AGCATGGGGG AGCCCGTGAT CAAGTGCGAG TTCGAGAAGG TCATCAGCAT GGAGTACATG GTCTACTTCA ACTTCTTTGT GTGGGTGCTG CCCCCGCTTC TCCTCATGGT CCTCATCTAC CTGGAGGTCT TCTACCTAAT CCGCAAGCAG CTCAACAAGA AGGTGTCGGC CTCCTCCGGC GACCCGCAGA AGTACTATGG GAAGGAGCTG AAGATCGCCA AGTCGCTGGC CCTCATCCTC TTCCTCTTTG CCCTCAGCTG GCTGCCTG CACATCCTCA ACTGCATCAC 50 CCTCTTCTGC CCGTCCTGCC ACAAGCCCAG CATCCTTACC TACATTGCCA TCTTCCTCAC GCACGGCAAC TCGGCCATGA ACCCCATTGT CTATGCCTTC CGCATCCAGA AGTTCCGCGT CACCTTCCTT AAGATTTGGA ATGACCATTT CCGCTGCCAG CCTGCACCTC CCATTGACGA GGATCTCCCA GAAGAGAGGC CTGATGACTA G ATGAGTGTCA GAAGTGTGAA GGGTGCCTGT TCTGAATCCC AGAGCCTCCT CTCCCTCTGT GAGGCTGGCA GGTGAGGAAG GGTTTAACCT CACTGGAAGG AATCCCTGGA GCTAGCGGCT GCTGAAGGCG TCGAGGTGTG 55 GGGGCACTTG GACAGAACAG TCAGGCAGCC GGGAGCTCTG CCAGCTGG TGACCTTGGG CCGGGCTGGG AGCGCTGCGG CGGGAGCCGG AGGACTATGA GCTGCCGCGC GTTGTCCAGA GCCCAGCCCA GCCCTACGCG WO 00/62736 PCT/USOO/08020 20 CGCGGCCCGG AGCTCTGTTC CCTGGAACTT TGGGCACTGC CTCTGGGACC CCTGCCGGCC AGCAGGCAGG ATGGTGCTTG CCTCGTGCCC CTTGGTGCCC GTCTGCTGAT GTGCCCAGCC TGTGCCCGCC ATGCCGCCCT CCATCTCAGC TTTCCAGGCC GCCTACATCG GCATCGAGGT GCTCATCGCC CTGGTCTCTG TGCCCGGGAA CGTGCTGGTG ATCTGGGCGG TGAAGGTGAA CCAGGCGCTG CGGGATGCCA CCTTCTGCTT CATCGTGTCG 5 CTGGCGGTGG CTGATGTGGC CGTGGGTGCC CTGGTCATCC CCCTCGCCAT CCTCATCAAC ATTGGGCCAC AGACCTACTT CCACACCTGC CTCATGGTTG CCTGTCCGGT CCTCATCCTC ACCCAGAGCT CCATCCTGGC CCTGCTGGCA ATTGCTGTGG ACCGCTACCT CCGGGTCAAG ATCCCTCTCC GGTACAAGAT GGTGGTGACC CCCCGGAGGG CGGCGGTGGC CATAGCCGGC TGCTGGATCC TCTCCTTCGT GGTGGGACTG ACCCCTATGT TTGGCTGGAA CAATCTGAGT GCGGTGGAGC GGGCCTGGGC AGCCAACGGC AGCATGGGGG AGCCCGTGAT 10 CAAGTGCGAG TTCGAGAAGG TCATCAGCAT GGAGTACATG GTCTACTTCA ACTTCTTTGT GTGGGTGCTG CCCCCGCTTC TCCTCATGGT CCTCATCTAC CTGGAGGTCT TCTACCTAAT CCGCAAGCAG CTCAACAAGA AGGTGTCGGC CTCCTCCGGC GACCCGCAGA AGTACTATGG GAAGGAGCTG AAGATCGCCA AGTCGCTGGC CCTCATCCTC TTCCTCTTTG CCCTCAGCTG GCTGCCTTTG CACATCCTCA ACTGCATCAC CCTCTTCTGC CCGTCCTGCC ACAAGCCCAG CATCCTTACC TACATTGCCA TCTTCCTCAC GCACGGCAAC TCGGCCATGA 15 ACCCCATTGT CTATGCCTTC CGCATCCAGA AGTTCCGCGT CACCTTCCTT AAGATTTGGA ATGACCATTT CCGCTGCCAG CCTGCACCTC CCATTGACGA GGATCTCCCA GAAGAGAGGC CTGATGACTA GACCCCGCCT TCCGCTCCCA CCAGCCCACA TCCAGTGGGG TCTCAGTCCA GTCCTCACAT GCCCGCTGTC CCAGGGGTCT CCCTGAGCCT GCCCCAGCTG GGCTGTTGGC TGGGGGCATG GGGGAGGCTC TGAAGAGATA CCCACAGAGT GTGGTCCCTC CACTAGGAGT TAACTACCCT ACACCTCTGG GCCCTGCAGG AGGCCTGGGA GGGCAAGGGT 20 CCTACGGAGG GACCAGGTGT CTAGAGGCAA CAGTGTTCTG AGCCCCCACC TGCCTGACCA TCCCATGAGC AGTCCAGCGC TTCAGGGCTG GGCAGGTCCT GGGGAGGCTG AGACTGCAGA GGAGCCACCT GGGCTGGGAG AAGGTGCTTG GGCTTCTGCG GTGAGGCAGG GGAGTCTGCT TGTCTTAGAT GTTGGTGGTG CAGCCCCAGG ACCAAGCTTA AGGAGAGGAG AGCATCTGCT CTGAGACGGA TGGAAGGAGA GAGGTTGAGG ATGCACTGGC CTGTTCTGTA GGAGAGACTG GCCAGAGGCA GCTAAGGGGC AGGAATCAAG GAGCCTCCGT TCCCACCTCT 25 GAGGACTCTG GACCCCAGGC CATACCAGGT GCTAGGGTGC CTGCTCTCCT TGCCCTGGGC CAGCCCAGGA TTGTACGTGG GAGAGGCAGA AAGGGTAGGT TCAGTAATCA TTrCTGATGA TTTGCTGGAG TGCTGGCTCC ACGCCCTGGG GAGTGAGCTT GGTGCGGTAG GTGCTGGCCT CAAACAGCCA CGAGGTGGTA GCTCTGAGCC CTCCTTCTTG CCCTGAGCTT TCCGGGGAGG AGCCTGGAGT GTAATTACCT GTCATCTGGG CCACCAGCTC CACTGGCCCC CGTTGCCGGG CCTGGACTGT CCTAGGTGAC CCCATCTCTG CTGCTTCTGG GCCTGATGGA 30 GAGGAGAACA CTAGACATGC CAACTCGGGA GCATTCTGCC TGCCTGGGAA CGGGGTGGAC GAGGGAGTGT CTGTAAGGAC TCAGTGTTGA CTGTAGGCGC CCCTGGGGTG GGTTTAGCAG GCTGCAGCAG GCAGAGGAGG AGTACCCCCC TGAGAGCATG TGGGGGAAGG CCTTGCTGTC ATGTGAATCC CTCAATACCC CTAGTATCTG GCTGGGTTTT CAGGGGCTTT GGAAGCTCTG TTGCAGGTGT CCGGGGGTCT AGGACTT7AG GGATCTGGGA TCTGGGGAAG GACCAACCCA TGCCCTGCCA AGCCTGGAGC CCCTGTGTTG GGGGGCAAGG TGGGGGAGCC 35 TGGAGCCCCT GTGTGGGAGG GCGAGGCGGG GGAGCCTGGA GCCCCTGTGT GGGAGGGCGA GGCGGGGGAT CCTGGAGCCC CTGTGTCGGG GGGCGAGGGA GGGGAGGTGG CCGTCGGTTG ACCTTCTGAA CATGAGTGTC AACTCCAGGA CTTGCTTCCA AGCCCTT'CCC TCTGTTGGAA ATTGGGTGTG CCCTGGCTCC CAAGGGAGGC CCATGTGACT AATAAAAAAC TGTGAACCCT CGCATTTGTG TITTAATAAA AGAATCTGGA AGATAAATAG TCTTGAAGAG AGACAAAGGA AGGAAAATTT AAATCCTTAG ATTCAAGCAG AAGAATTCCA TGTGGAAGGT 40 TTGGGTTGTT GTTGTFGTTG TTTGGTGTGT TTTGTTTT TTTGTTT TGTTrT TGAGATGGAG TCTCGCTGTG TTACCGGGAG CGACAGAGCC GCACGGCCGA GTCGAGTCCC AGCCAGCTAC CATCCCTCTG GAGCTTACCG GCCGGCCTTG GCTTCCCCAG GAATCCCTGG AGCTAGCGGC TGCTGAAGGC GTCGAGGTGT GGGGGCACTT GGACAGAACA GTCAGGCAGC CGGGAGCTCT GCCAGCTTTG GTGACCTTGG GTGCTTGCCT CGTGCCCCTT GGTGCCCGTC TGCTGATGTG CCCAGCCTGT GCCCGCCATG CCGCCCTCCA TCTCAGCTTT 45 CCAGGCCGCC TACATCGGCA TCGAGGTGCT CATCGCCCTG GTCTCTGTGC CCGGGAACGT GCTGGTGATC TGGGCGGTGA AGGTGAACCA GGCGCTGCGG GATGCCACCT TCTGCTTCAT CGTGTCGCTG GCGGTGGCTG ATGTGGCCGT GGGTGCCCTG GTCATCCCCC TCGCCATCCT CATCAACATT GGGCCACAGA CCTACTTCCA CACCTGCCTC ATGGTTGCCT GTCCGGTCCT CATCCTCACC CAGAGCTCCA TCCTGGCCCT GCTGGCAATT GCTGTGGACC GCTACCTCCG GGTCAAGATC CCTCTCCGGT ACAAGATGGT GGTGACCCCC CGGAGGGCGG 50 CGGTGGCCAT AGCCGGCTGC TGGATCCTCT CCTTCGTGGT GGGACTGACC CCTATGTTTG GCTGGAACAA TCTGAGTGCG GTGGAGCGGG CCTGGGCAGC CAACGGCAGC ATGGGGGAGC CCGTGATCAA GTGCGAGTTC GAGAAGGTCA TCAGCATGGA GTACATGGTC TACTTCAACT TCTTTGTGTG GGTGCTGCCC CCGCTTCTCC TCATGGTCCT CATCTACCTG GAGGTCTTCT ACCTAATCCG CAAGCAGCTC AACAAGAAGG TGTCGGCCTC CTCCGGCGAC CCGCAGAAGT ACTATGGGAA GGAGCTGAAG ATCGCCAAGT CGCTGGCCCT CATCCTCTTC 55 CTCTTTGCCC TCAGCTGGCT GCCTTFGCAC ATCCTCAACT GCATCACCCT CTTCTGCCCG TCCTGCCACA AGCCCAGCAT CCTTACCTAC ATTGCCATCT TCCTCACGCA CGGCAACTCG GCCATGAACC CCATTGTCTA WO 00/62736 PCT/USOO/08020 21 TGCCTCCGC ATCCAGAAGT TCCGCGTCAC CTTCCTTAAG ATTTGGAATG ACCATTTCCG CTGCCAGCCT GCACCTCCCA TTGACGAGGA TCTCCCAGAA GAGAGGCCTG ATGACTAGAC CCCGCCTrCC GCTCCCACCG CCCACATCCA GTGGGGTCTC AGTCCAGTCC TCACATGCCC GCTGTCCCAG GGGTCTCCCT GAGCCTGCCC CAGCTGGGCT GTTGGCTGGG GGCATGGGGG AGGCTCTGAA GAGATACCCA CAGAGTGTGG TCCCTCCACT 5 AGGAGTTAAC TACCCTACAC CTCTGGGCCC TGCAGGAGGC CTGGGAGGGC AAGGGTCCTA CGGAGGGACC AGGTGTCTAG AGGCAACAGT GTTCTGAGCC CCCACCTGCC TGACCATCCC ATGAGCAGTC CAGAGCTTCA GGGCTGGGCA GGTCCTGGGG AGGCTGAGAC TGCAGAGGAG CCACCTGGGC TGGGAGAAGG TGCTTGGGCT TCTGCGGTGA GGCAGGGGAG TCTGCTTGTC TTAGATGTTG GTGGTGCAGC CCCAGGACCA AGCTTAAGGA GAGGAGAGCA TCTGCTCTGA GACGGATGGA AGGAGAGAGG TTGAGGATGC ACTGGCCTGT TCTGTAGGAG 10 AGACTGGCCA GA CCCAGCCCCG AGGCTCAGAA GCGGCAGGCG GAGGCGCGGT CCGGGCGCTA TGGCCATGCC CGGCGGGTCT CACGCGGCTG CCCCTCGCCC GGCGCGCCTT CGGTAGGGGG CGCCCGGGGC CCAGCTGGCC CGGCCATGCT GCTGGAGACA CAGGACGCGC TGTACGTGGC GCTGGAGCTG GTCATCGCCG CGCTTTCGGT GGCGGGCAAC GTGCTGGTGT GCGCCGCGGT GGGCACGGCG AACACTCTGC AGACGCCCAC CAACTACTTC CTGGTGTCCC TGGCTGCGGC CGACGTGGCC GTGGGGCTCT TCGCCATCCC CTTTGCCATC 15 ACCATCAGCC TGGGCTTCTG CACTGACTTC TACGGCTGCC TCTTCCTCGC CTGCTTCGTG CTGGTGCTCA CGCAGAGCTC CATCTTCAGC CTTCTGGCCG TGGCAGTCGA CAGATACCTG GCCATCTGTG TCCCGCTCAG GTATAAAAGT T7GGTCACGG GGACCCGAGC AAGAGGGGTC ATTGCTGTCC TCTGGGTCCT TGCCTTTGGC ATCGGATTGA CTCCATTCCT GGGGTGGAAC AGTAAAGACA GTGCCACCAA CAACTGCACA GAACCCTGGG ATGGAACCAC GAATGAAAGC TGCTGCCTTG TGAAGTGTCT CTTTGAGAAT GTGGTCCCCA TGAGCTACAT 20 GGTATATTTC AATTCTTTG GGTGTGTTCT GCCCCCACTG CTTATAATGC TGGTGATCTA CATTAAGATC TTCCTGGTGG CCTGCAGGCA GCTTCAGCGC ACTGAGCTGA TGGACCACTC GAGGACCACC CTCCAGCGGG AGATCCATGC AGCCAAGTCA CTGGCCATGA TTGTGGGGAT TTTTGCCCTG TGCTGGTTAC CTGTGCATGC TGTTAACTGT GTCACTCTTT TCCAGCCAGC TCAGGGTAAA AATAAGCCCA AGTGGGCAAT GAATATGGCC ATTCTTCTGT CACATGCCAA TTCAGTTGTC AATCCCATTG TCTATGCTTA CCGGAACCGA GACTTCCGCT 25 ACACTTTTCA CAAAATTATC TCCAGGTATC TTCTCTGCCA AGCAGATGTC AAGAGTGGGA ATGGTCAGGC TGGGGTACAG CCTGCTCTCG GTGTGGGCCT ATGATCTAGG CTCTCGCCTC TTCCAGGAGA AGATACAAAT CCACAAGAAA CAAAGAGGAC ACGGCTGGTT TrCATTGTGA AAGATAGCTA CACCTCACAA GGAAATGGAC TGCCTCTCTT GAGCACTTCC CTGGAGCTAC CACGTATCTA GCTAATATGT ATGTGTCAGT AGTAGCACCA AGGATTGACA AATATATTTA TGATCTATTC AGCTGCTTT ACTGTGTGGA TTATGCCAAC AGCTTGAATG 30 GATTCTAACA GACTCTTTTG TTTAAAAG TCTGCCTTGT TTATGGTGGA AAATTACTGA AACTATTTTA CTGTGAAACA GTGTGAACTA TTATAATGCA AATACTT AACTTAGAGG CAATGGAAAA ATAAAAGTTG ACTGTACTAA AAATGTATAC TTGTrGCCAG GAAGGTGACC TCAAAAATTA AAAGTATAAT TATTCGGCCG GGCATGGTGG CTCACACCTG TAATTCCAGC ACTGGGAG GCCAAGGCAG GCGGATCACG AGGTCAGGAG TTCAAAACCA GCCTGTCCAA TATAGTG GGGCAATTTG TTAGTTATCC GCCGCCACCA AGACGCGGCA 35 CGGCGCCTGG ACCGGAGGGG CCCCGCGCGG GCGCGAACTT TGGGCTCGGG CGAGTGGGTG GTGCTCCGCC CAGCCCGAGA CGGGCGGGCG CGCGGGCCAA TGGGTGCCGC CTCTTGGCCG CGGGGGGCCC CGACCCGTGG GTCCCGGCCA CCAGCGCCCC AGCCCCGAGG CTCAGAAGCG GCAGGCGGAG GCGCGGTCCG GGCGCTATGG CCATGCCCGG CGGGTCTCAC GCGGCTGCCC CTCGCCCGGC GCGCCTrCGG TAGGGGGCGC CCGGGGCCCA GCTGGCCCGG CCATGCTGCT GGAGACACAG GACGCGCTGT ACGTGGCGCT GGAGCTGGTC ATCGCCGCGC 40 TTTCGGTGGC GGGCAACGTG CTGGTGTGCG CCGCGGTGGG CACGGCGAAC ACTCTGCAGA CGCCCACCAA CTACTTCCTG GTGTCCCTGG CTGCGGCCGA CGTGGCCGTG GGGCTCTTCG CCATCCCCTT TGCCATCACC ATCAGCCTGG GCTTCTGCAC TGACTTCTAC GGCTGCCTCT TCCTCGCCTG CTTCGTGCTG GTGCTCACGC AGAGCTCCAT CTrCAGCCTT CTGGCCGTGG CAGTCGACAG ATACCTGGCC ATCTGTGTCC CGCTCAGGTA TAAAAGTTTG GTCACGGGGA CCCGAGCAAG AGGGGTCATT GCTGTCCTCT GGGTCCTrGC CTTTGGCATC 45 GGATTGACTC CATTCCTGGG GTGGAACAGT AAAGACAGTG CCACCAACAA CTGCACAGAA CCCTGGGATG GAACCACGAA TGAAAGCTGC TGCCTTGTGA AGTGTCTCTT TGAGAATGTG GTCCCCATGA GCTACATGGT ATA'TrCAAT TrCTTTGGGT GTGTTCTGCC CCCACTGCTT ATAATGCTGG TGATCTACAT TAAGATCTTC CTGGTGGCCT GCAGGCAGCT TCAGCGCACT GAGCTGATGG ACCACTCGAG GACCACCCTC CAGCGGGAGA TCCATGCAGC CAAGTCACTG GCCATGATTG TGGGGATT TGCCCTGTGC TGGTTACCTG TGCATGCTGT 50 TAACTGTGTC ACTCTTTTCC AGCCAGCTCA GGGTAAAAAT AAGCCCAAGT GGGCAATGAA TATGGCCATT CTTCTGTCAC ATGCCAATTC AGTTGTCAAT CCCATTGTCT ATGCTTACCG GAACCGAGAC TTCCGCTACA CTTCACAA AATTATCTCC AGGTATCTTC TCTGCCAAGC AGATGTCAAG AGTGGGAATG GTCAGGCTGG GGTACAGCCT GCTCTCGGTG TGGGCCTATG ATCTAGGCTC TCGCCTCTTC CAGGAGAAGA TACAAATCCA CAAGAAACAA AGAGGACACG GCTGGTTC ATTGTGAAAG ATAGCTACAC CTCACAAGGA AATGGACTGC 55 CTCTCTTGAG CACTTCCCTG GAGCTACCAC GTATCTAGCT AATATGTATG TGTCAGTAGT AGGCTCCAAG GATTGACAAA TATATTTATG ATCTATTCAG CTGCTTTTAC TGTGTGGATT ATGCCAACAG CTTGAATGGA WO 00/62736 PCT/USOO/08020 22 71?CTAACAGA CTC'FrTTGTr TrAAAAGTC TGCC'I1GTT1T ATGGTGGAAA ATTACTGAAA CTATI'TTACT GTGAAACAGT GTGAACTATT ATAATGCAAA TACTITFAA =TAGAGGCA ATGGAAAAAT AAAAGTTGAC TGTACTAAAA ATG GAATTCCCAG ATGGGCAGAG GTGGCTGGGC TGGTGACCCT AAGTGTGTCT CCTGCCT'FTA TTCTCTCTAG TGGGTTATlC TITCATGTGG TATCTrGCCT ACAGCATGCT GTG1TTGGAC 5 ACAAACCCCT TTCCTTGG'rr TCTCTGACCC AGCTGAGATG GACTGATTCC AAAAGAACTC ACCTATGTAC TGGGGTAGGG GAGGGAGGGT TITGCAGT A'LTTAACTAA GGTrCAAAGA GTGCTATATA GTGAGAAAGG CTTC1TIT TI-rrTT YfTTTGGCA GAGTGCTGCC TCCTAGAAAT TTCTCTTGGT AACTrCC'rrC TCTGAAGCAC AGATAAAGAA AACAATT1ACA GTAGAAACAT TT1ATGAGGGA CACATTGGAG GCCGATGAAG C'T=rCAAGT TCCAGCAGTG CAGGGATGTG GGCAGAACTG ACA'ITGGAAA ATACTAGAAT GATGGAAATT 10 CAGTTGGAGA GGACTGCCCT =LhAATGTC TGGGGAGTCT GCTCAGGGAG AAATGACAAG TCTGGCGGGG ACAAGTATGG GATTTGGTAA GACTTGGATC AACTTGGGAT ACAGGGTGGG GGTCGGGAGT GGAATCAATG AATGATGCCA GAGCAGATCA ACTAACAAGA GGACCCTGAT GAGCCCCAGG CAGAGGCGTC TCCCTI7ATGC CCCACTCTGA AGTGTTTGTT AGTAAACACC AGAACGCCAT TGTT'TACT GCTGAATIT ATTTT1GGGCT GTACATATT AGATGCTTAA GGTAAAAATG ATAAAGCCCT CAAGCCACTG TGTGGGTF-rG GGTCCAAGTG 15 TrCC'rFCTrG CTGCCTCTCT AACACGCCTG GTTAAAATAA TCCCTITGGA TGGTGCTGAG AAGCACCTGA ACCAAGTGGG TCCCCAAATA ACAATGGCGT GCAAGTGTCT GG'I1CCCAGA AG'ITGGTGAC TAGGTAAGCA GCTI1?CAGGGA GAGGGGGCTG ATT1CCCAGAC AGTCGCCTGT TCCTGCGGGG ATGGGGCTGA GGCTTGGGGA ATGTGGGCAG GAGGATATGC CAMFGATTC TGTrGCACAC GTTCT'=CC CTTCTJTCTG TATGTCTGGT CATTCTGCTA TTCTGTCGT-r CCTCACATAG GTrGGACA'rr GGCCGGCTGC CAGCATAAGT GCCAGTGTGA 20 rT=GCTAGG TGTGAGCTGA GAAAGAGAGG TGGAGGCTAA GCAGGTGTGA TGcTTrCTCAG AGGTGCTGAG ThITGCCCT TCTGAGCAGG GAATC'=GC T-rATCCC'lTr GACCAAGGAT CTGCTGCA AAGGCTGGGT ATCGGCTGTG CTCAGCAAAG CGTCAACTCG TGCAAGAACT TAGCAGGAAT AGT~rCTGGCT AAGGTTAGGA GGCTGCCACC AAAGTCTCTT =TIL1CCT CTGCTTCTCC CGT'I17GCCTC CTTATCATGA GATCTTTITG CTAAGCTGGC AGAAAGAYJTG CATAGTCAGT GCTICCAGCT CTGCTCCCAC CTGATCCTGC ACTGTCCTCT 25 GGTCCCTGAA TGAATGAACT CTGATACCCA ATCTTGTCTC GAGCCTTFCTC TATGCCACTC ATGGCTCCTC TTCTGCTCF'T TCCATCTIT TGCTGAGAGT TCTGAGCTCT GTACTTCCTC TTGGCCCATC TCACL1CCTG AAACACCCCT GAAGAGGGTT GCflATCL1G ATGGAACTCA AAAAGCCAAA AAGCTGCAGG CAGAGGCG'I1 GAGGACATCT GTTTGGGGAA CTAAGAGCAG CAGCACTrTC AGATTCAGTC CATATAGAGC TGTCCTACAG CATTCTGGAA ACTTGAGGAT GTGCGGTGCA TAAAGGGGCT GGAAGTGACC CACCTGTGAT GAGCCCTITC 30 TAAGGAGAAG GGTrTCCAAG AGATCACCCC ACCAGAAAAG GGTAGGAATG AGCAAGT7GG GAATITTAGA CTGTCACTGC ACATGGACCT CTGGGAAGAC GTCTGGCGAG AGCTAGGCCC ACTGGCCCTA CAGACGGATC TTGCTGGCTC ACCTGTCCCT GTGGAGGTTC CCCTGGGAAG GCAAGATGCC CAACAACAGC ACTGCTCTGT CAT'rGGCCAA TGTTACCTAC ATCACCATGG AAAYTTCAT TGGACTCTGC GCCATAGTGG GCAACGTGGT GGTCATCTGC GTGGTCAAGC TGAACCCCAG CCTGCAGACC ACCACCTTCT A'ITrCATTGT CTCTCTAGCC 35 CTGGCTGACA TTGCTGTTGG GGTGCTGGTC ATGCC'IMGG CCA'FrGTrGT CAGCCTGGGC ATCACAATCC ACTTCTACAG CTGCCTI1TT ATGACTTGCC TACTGCTTAT CTTTACCCAC GCCTCCATCA TGTCCTTGCT GGCCATCGCT GTGGACCGAT ACUTGCGGGT CAAGMTACC GTCAGGTAGC CTGCGGCGTG GGGTGGGCAG CAATTGAGGC AGCTGGGAAA TGAGGCTACA AAGCCAGAGC CTGCTGAA117 TrA'm'TGGA CTGTACATAT TTAGATGCTT AAGGTAAAAA TGATAAAGCC CTCAAGCCAC TGTGTGGGTT GGGTCCAAGT GTTCCTTGCT 40 GCTGCCTCTC TAACACGCCT GGTTAAAATA ATCCCTrGG ATGGTGCTGA GAAGCACCTG AACCAAGTGG GTCCCCAAAT AACTATGGCG TGCAAGTGTC TGGTTCCCAG AAGTT1GGTGA CTAGGTAAGC GACTCAGGGA GAGGGGCTGA Y17CCCAGACA GTCGCCTGTT1 CCTGCTGGGA TGGGGCTGAG GCTTGGGGAA TGTGGGCAGG AGGATATGCC A'TTGATTCT GTTGCACACG TTCTTTTCCC TTCT1TCTGT ATGTCTGGTC ATTCTGCTAT TCTGTCGT'rC CTCACATAGG TTGGACATTG GCCGGCTGCC AGCATAAGTG CCAGTGTGAT TFTGCTAGGG 45 TGTGAGCTGA GAAAGAGAGG TGGAGGCTAA GCAGGTGTGA TGCTrCTCAG AGGTGCTGAG TITTGCCCT TCTGAGCAGG GAATCTGC 'ITATCCC'IT GACCAAGGAT C'TTGCTCCA AAGGCTGGGT ATCGGCTGTG CTCAGCAAAG CGTCAACTCG TGCAAGAACT TAGCAGGAAT AGTTCTGGCT AAGGTTAGGA GGCTGCCACC AAAGTCTCTT TfGTTCCT CTGCTTCTCC CGTITGCCTC C'ITATCATGA GATCTYrTTG CTAAGCTGGC AGAAAGATTG CATAATCAGT GCTrCCAGCT CCGCTCCCAC CTGATCCTGC ACTGTCCTCT GGTCCCTGAA 50 TGAATGAACT CTGATACCCA ATCTTGTCTC GAGC=TCTC TATGCCACTC ATGGCTCCTC TTCTGCTCTT TCCATCTITI TGCTGAGAGT TACTGAGCTC TGTACTI7CCT CTTGGCCCAT CTCAC'ITCCT GAAACACCCC TGAAGAGGGT TGC117ATCTT1 GATGGAACTC AAAAAGCCAA AAAGCTGCAG GCAGAGGCGT TGAGGACATC TGTIGGGGA ACTAAGAGCA GCAGCAC=I CAGATI7CAGT CCATATAGAG CTGTCCTACA GCA'ITCTGGA AACTTGAGGA TGTGCGGTGC ATAAAGGGGC TGGAAGTGAC CCACCTGTGA TGAGCCCTr CTAAGGAGAA 55 GGGTCCAA GAGATCACCC CACCAGAAAA GGGTAGGAAT GAGCAAG FTG GGAAYITTAG ACTGTCACTG CACATGGACC TCTGGGAAGA CGTCTGGCGA GAGCTAGGCC CACTGGCCCT ACAGACGGAT C'L1?GCTGGCT WO 00/62736 PCT/USOO/08020 23 CACCTGTCCC TGTGGAGGTT CCCCTGGGAA GGCAAGATGC CCAACAACAG CACTGCTCTG CGAATTCGGG GGACATCTGT TTGGGGAACT AAGAGCAGCA GCACTTTCAG ATTCAGTCCA TATAGAGCTG TCCTACAGCA TTCTGGAAAC TTGAGGATGT GCGGTGCATA AACGGGCTGG AAGTGACCCA CCTGTGATGA GCCCTTTCTA AGGAGAAGGG TTTCCAAGAG ATCACCCCAC CAGAAAAGGG TAGGAATGAG CAAGTTGGGA AYTTAGACT 5 GTCACTGCAC ATGGACCTCT GGGAAGACGT CTGGCGAGAG CTAGGCCCAC TGGCCCTACA GACGGATCTT GCTGGCTCAC CTGTCCCTGT GGAGGTTCCC CTGGGAAGGC AAGATGCCCA ACAACAGCAC TGCTCTGTCA TTGGCCAATG TTACCTACAT CACCATGGAA ATTTTCATTG GACTCTGCGC CATAGTGGGC AACGTGCTGG TCATCTGCGT GGTCAAGCTG AACCCCAGCC TGCAGACCAC CACCTTCTAT TTCATTGTCT CTCTAGCCCT GGCTGACATT GCTGTTGGGG TGCTGGTCAT GCCTTTGGCC ATTGTTGTCA GCCTGGGCAT CACAATCCAC 10 TTCTACAGCT GCCTTTTTAT GACTTGCCTA CTGCTTATCT TTACCCACGC CTCCATCATG TCCTTGCTGG CCATCGCTGT GGACCGATAC TTGCGGGTCA AGCTTACCGT CAGATACAAG AGGGTCACCA CTCACAGAAG AATATGGCTG GCCCTGGGCC TTTGCTGGCT GGTGTCATTC CTGGTGGGAT TGACCCCCAT GTTTGGCTGG AACATGAAAC TGACCTCAGA GTACCACAGA AATGTCACCT TCCTTTCATG CCAATTTGTr TCCGTCATGA GGATGGACTA CATGGTATAC TTCAGCTTCC TCACCTGGAT TTTCATCCCC CTGGTTGTCA TGTGCGCCAT 15 CTATCTTGAC ATCTTACA TCATTCGGAA CAAACTCAGT CTGAACTTAT CTAACTCCAA AGAGACAGGT GCATTTTATG GACGGGAGTT CAAGACGGCT AAGTCCTTGT TTCTGGTTCT TTrCTTGTTT GCTCTGTCAT GGCTGCCTTT ATCTCTCATC AACTGCATCA TCTACTTTAA TGGTGAGGTA CCACAGCTTG TGCTGTACAT GGGCATCCTG CTGTCCCATG CCAACTCCAT GATGAACCCT ATCGTCTATG CCTATAAAAT AAAGAAGTTC AAGGAAACCT ACCTTTTGAT CCTCAAAGCC TGTGTGGTCT GCCATCCCTC TGATTCTTTG GACACAAGCA 20 TTGAGAAGAA TTCTGAGTAG TTATCCATCA GAGATGACTC TGTCTCATTG ACCTTCAGAT TCCCCATCAA CAAACACTTG AGGGCCTGTA TGCCTGGGCC AAGGGATTT TACATCCTTG ATTACTTCCA CTGAGGTGGG AGCATCTCCA GTGCTCCCCA ATTATATCTC CCCCACTCCA CTACTCTCTT CCTCCACTTC ATTTTTCCTT TGTCCTTTCT CTCTAATTCA GTGTTGGA GGCCTGACTT GGGGACAACG TATTATTGAT ATTATTGTCT GTTTTCCTTC TTCCCAATAG AAGAATAAGT CATGGAGCCT GAAGGGTGCC TAGTTGACTT ACTGACAAAA 25 GGCTCTAGTT GGGCTGAACA TGTGTGTGGT GGTGACTCAT TTCCATGCCA TTGTGGAATT GAGCAGAGAA CCTGCTCTCG GAGGATGCCT AGGAGATGTT GGGAACAGAA GAAATAAACT GAGTTTAAGG GGGACTTAAA CTGCTGAATT C CAGATTCACA AACTGCAGGA CTGGGCAGGG AGCAGACAGT GAGCAAACGC CAGCAGGGCT GCTGTGAATT TGTGTAAGGA TTGAGGGACA GTTGCTTC AGCATGGGCC CAGGAATGCC AAGGAGACAT CTATGCACGA CCTTGGGAAA TGAGTTGATG TCTCCGGTAA AACACCGGAG ACTAATTCCT GCCCTGCCCA 30 ATTTTGCAGG GAGCATGGCT GTGAGGATGG GGTGAACTCA CGCACAGCCA AGGACTCCAA AATCACAACA GCATTACTGT TCTrATTTGC TGCCACACCT GAGCCAGCCT GCTCCTTCCC AGGAGTGGAG GAGGCCTGGG GGGAGGGAGA GGAGTGACTG AGCTTCCCTC CCGTGTGTTC TCCGTCCCTG CCCCAGCAAG ACAACTTAGA TCTCCAGGAG AACTGCCATC CAGCTTTGGT GCAATGGCTG AGTGCACAAG TGAGTTGTTG CCCTGGGTTT CTTTAATCTA TTCAGCTAGA ACTTTGAAGG ACAATrCTT GCATTAATAA AGGTTAAGCC CTGAGGGGTC 35 CCTGATAACA ACCTGGAGAC CAGGATTA TGGCTCCCCT CACTGATGGA CAAGGAGGTC TGTGCCAAAG AAGAATCCAA TAAGCACATA TTGAGCACTT GCTGTATATG CAGTATTGAG CACTGTAGGC AAGACCCAAG AAAGAGAAGG AGCCATCTCC ATCTTGAAGG AACTCAAAGA CTCAAGTGGG AACGACTGGG CACTGCCACC ACCAGAAAGC TGTTCGACGA GACGGTCGAG CAGGGTGCTG TGGGTGATAT GGACAGCAGA AGGGGGAGAC CAAGGTTCCA GCTCAACCAA TAACTATTGC ACAACCACCT GTCCCTGCCT CAGTTCCCTT TTATGTAACA 40 TGAAGTCGTT GTGAGGGTTA AAGGCAGTAA CAGGTATAAA GTACTTAGAA AAGCAAAGGG TGCTACGTAC ATGTGAGGCA TCATTACGCA GACGTAACTG GGATATGT ACTATAAGGA AAAGACACTG AGGTCTAGAA ATAGCTCCGT GGAGCAGAAT CAGTATTGGG AGCCGGTGGC GGTGTGAAGC ACCAGTGTCT GGCACACAGT. AGGTGCTCAT TGGCTCCCTT CCACCTGTCA TTCCCACCAC CCTGAGGCCC CAACCGCCAC ACACACAGGA GCATTTGGAG AGAAGGCCAT GTCTTCAAAG TCTGATTTGT GATGAGGCAG AGGAAGATAT TTCTAATCGG 45 TCTTGCCCAG AGGATCACAG TGCTGAGACC CCCCACCACC AGCCGGTACC TGGGAAGGGG GAGAGTGCAG GCCTGCTCAG GGACTGTTCC TGTCTCAGCA ACCAAGGGAT TGTTCCTGTC AATCAATGGT TTATTGGAAG GTGGCCCAGT ATGAGCCCTA GAAGAGTGTG AAAAGGAATG GCAATGGTGT TCACCATCGG CAGTGCCAGG GCAGCACTCA TTCACTTGAT AAATGAATAT TTATTAGCTG GTTGGAGAGC TAGAACCTGG AGAGCTAGAA CCTGGAGAAC TAGAACCTGG AGGGCTAGAA CCTGGAGAGG CTAGAACCAA GAAGGGCTAG AACCTGGAGG 50 GGCTAGAACC TAGAGAAGCT AAAACCTGAG CTAGAAGCTG GAGGACTAGA ACCTGGAGGG CTGGAATCTG AAGGGCTAGA ACCTGGAGGG CTGGAATCTG GAGAGCTAGA ACCTGGAGGG CTAGAACCTG GAGGGCTAGA ACCTAGAAGG GCTAGAACCT GGAGGGCTGG AATCTGGAGA GCTAGAACCT GGAGGGCTAG AACCTGGAGG GCTAGAACCT AGAAGGGCTA GAACCTGGAG GGCTAGAACC TGGCAGGTTA GAACCTAGAA GGGCTAGAAC CTGGAGAGCC AGAACCTGGA GGGCTAGAAC CTGGAAGGGC TAGAACCTGT AGAGCTAGAA CATGGAGAGC 55 TAGAACCCGG CAGGCTAGAA CCTGGCAAGC TAGAACCTGG AGGGAATGAA CCTGGAGGGC TAGAACCTGG AGAATGAGAA AAATTTACAT GGCAAAGAGC CCATAAATCC TGACCAATCC AACTCTGAAT TTTAAAGCAA WO 00/62736 PCT/USOO/08020 24 AAGCGTGAAA AAAAAGATTC CCTCCTTACC CCCAACCCAC TCTTTCC CACCACCCAC TCTCCTCTGC CTCAGTAAGT ATCTGGAGGA AGAAAACAGG TGAAAGAAGA AGTAAAAACC ATTTAGTATT AGTATTAGAA TGAAGTCAAA CTGTGCCACA CATGGTGAAT GAAAAAAAAA AAAAAGAGGC TGTGTTTGT CACACAGGGC AGTCATTCAG CACCAGAGCA CGTGATGGTC TGAGACTCTC TTAGGAGCAG AGCTCTGCCG CAATGGCCAT 5 GTGGGGATCC ACACCTGGTC TGAGGGGCAA CTGAGTCTGC GGGAGAAGAG CGGCCCTATG CATGGTGTAG ATGCCCTGAT AAAGAACATC TGTCCTGTGA AAGACTCAAT GAGCTGTTAT GTTGTAAACA GGAAGCATTT CACATCCAAA CGAGAAAATC ATGTAAACAT GTGTCTTTTC TGTAGAGCAT AATAAATGGA TGAGGTTTT GCAAAAAAAA AAAAAAAAA ATGCCGCCCT CCATCTCAGC TTTCCAGGCC GCCTACATCG GCATCGAGGT GCTCATCGCC CTGGTCTCTG TGCCCGGGAA CGTGCTGGTG ATCTGGGCGG TGAAGGTGAA CCAGGCGCTG 10 CGGGATGCCA CCTTCTGCTT CATCGTCTCG CTGGCGGTGG CTGATGTGGC CGTGGGTGCC CTGGTCATCC CCCTCGCCAT CCTCATCAAC ATTGGGCCAC AGACCTACTT CCACACCTGC CTCATGGTTG CCTGTCCGGT CCTCATCCTC ACCCAGAGCT CCATCCTGGC CCTGCTGGCA ATTGCTGTGG ACCGCTACCT CCGGGTCAAG ATCCCTCTCC GGTACAAGAT GGTGGTGACC CCCCGGAGGG CGGCGGTGGC CATAGCCGGC TGCTGGATCC TCTCCTTCGT GGTGGGACTG ACCCCTATGT TTGGCTGGAA CAATCTGAGT GCGGTGGAGC GGGCCTGGGC 15 AGCCAACGGC AGCATGGGGG AGCCCGTGAT CAAGTGCGAG TTCGAGAAGG TCATCAGCAT GGAGTACATG GTCTACTTCA ACTrCTTTGT GTGGGTGCTG CCCCCGCTrC TCCTCATGGT CCTCATCTAC CTGGAGGTCT TCTACCTAAT CCGCAAGCAG CTCAACAAGA AGGTGTCGGC CTCCTCCGGC GACCCGCAGA AGTACTATGG GAAGGAGCTG AAGATCGCCA AGTCGCTGGC CCTCATCCTC TT1CCTCTTTG CCCTCAGCTG GCTGCCTTTG CACATCCTCA ACTGCATCAC CCTCTTCTGC CCGTCCTGCC ACAAGCCCAG CATCCTTACC TACATTGCCA 20 TCTTCCTCAC GCACGGCAAC TCGGCCATGA ACCCCATTGT CTATGCCTTC CGCATCCAGA AGTTCCGCGT CACCTTCCTT AAGATTTGGA ATGACCATTT CCGCTGCCAG CCTGCACCTC CCATTGACGA GGATCTCCCA GAAGAGAGGC CTGATGACTA G ATGAGTGTCA GAAGTGTGAA GGGTGCCTGT TCTGAATCCC AGAGCCTCCT CTCCCTCTGT GAGGCTGGCA GGTGAGGAAG GGTTTAACCT CACTGGAAGG AATCCCTGGA GCTAGCGGCT GCTGAAGGCG TCGAGGTGTG GGGGCACTTG GACAGAACAG TCAGGCAGCC GGGAGCTCTG CCAGCTTTGG 25 TGACCTTGGG CCGGGCTGGG AGCGCTGCGG CGGGAGCCGG AGGACTATGA GCTGCCGCGC GTTGTCCAGA GCCCAGCCCA GCCCTACGCG CGCGGCCCGG AGCTCTGTTC CCTGGAACTT TGGGCACTGC CTCTGGGACC CCTGCCGGCC AGCAGGCAGG ATGGTGCTTG CCTCGTGCCC CTTGGTGCCC GTCTGCTGAT GTGCCCAGCC TGTGCCCGCC ATGCCGCCCT CCATCTCAGC TTTCCAGGCC GCCTACATCG GCATCGAGGT GCTCATCGCC CTGGTCTCTG TGCCCGGGAA CGTGCTGGTG ATCTGGGCGG TGAAGGTGAA CCAGGCGCTG CGGGATGCCA 30 CCTTCTGCTT CATCGTGTCG CTGGCGGTGG CTGATGTGGC CGTGGGTGCC CTGGTCATCC CCCTCGCCAT CCTCATCAAC ATTGGGCCAC AGACCTACTT CCACACCTGC CTCATGGTTG CCTGTCCGGT CCTCATCCTC ACCCAGAGCT CCATCCTGGC CCTGCTGGCA ATrGCTGTGG ACCGCTACCT CCGGGTCAAG ATCCCTCTCC GGTACAAGAT GGTGGTGACC CCCCGGAGGG CGGCGGTGGC CATAGCCGGC TGCTGGATCC TCTCCTTCGT GGTGGGACTG ACCCCTATGT TTGGCTGGAA CAATCTGAGT GCGGTGGAGC GGGCCTGGGC AGCCAACGGC 35 AGCATGGGGG AGCCCGTGAT CAAGTGCGAG TTCGAGAAGG TCATCAGCAT GGAGTACATG GTCTACTTCA ACTTCTTGT GTGGGTGCTG CCCCCGCTTC TCCTCATGGT CCTCATCTAC CTGGAGGTCT TCTACCTAAT CCGCAAGCAG CTCAACAAGA AGGTGTCGGC CTCCTCCGGC GACCCGCAGA AGTACTATGG GAAGGAGCTG AAGATCGCCA AGTCGCTGGC CCTCATCCTC TTCCTCTTTG CCCTCAGCTG GCTGCCTTTG CACATCCTCA ACTGCATCAC CCTCTTCTGC CCGTCCTGCC ACAAGCCCAG CATCCTTACC TACATTGCCA TCTTCCTCAC 40 GCACGGCAAC TCGGCCATGA ACCCCATTGT CTATGCCTTC CGCATCCAGA AGTTCCGCGT CACCTTCCTT AAGATTTGGA ATGACCATTT CCGCTGCCAG CCTGCACCTC CCATTGACGA GGATCTCCCA GAAGAGAGGC CTGATGACTA GACCCCGCCT TCCGCTCCCA CCAGCCCACA TCCAGTGGGG TCTCAGTCCA GTCCTCACAT GCCCGCTGTC CCAGGGGTCT CCCTGAGCCT GCCCCAGCTG GGCTGTTGGC TGGGGGCATG GGGGAGGCTC TGAAGAGATA CCCACAGAGT GTGGTCCCTC CACTAGGAGT TAACTACCCT ACACCTCTGG GCCCTGCAGG 45 AGGCCTGGGA GGGCAAGGGT CCTACGGAGG GACCAGGTGT CTAGAGGCAA CAGTGTTCTG AGCCCCCACC TGCCTGACCA TCCCATGAGC AGTCCAGCGC TrCAGGGCTG GGCAGGTCCT GGGGAGGCTG AGACTGCAGA GGAGCCACCT GGGCTGGGAG AAGGTGCTTG GGCTTCTGCG GTGAGGCAGG GGAGTCTGCT TGTCTTAGAT GTTGGTGGTG CAGCCCCAGG ACCAAGCTTA AGGAGAGGAG AGCATCTGCT CTGAGACGGA TGGAAGGAGA GAGGTTGAGG ATGCACTGGC CTGTTCTGTA GGAGAGACTG GCCAGAGGCA GCTAAGGGGC AGGAATCAAG 50 GAGCCTCCGT TCCCACCTCT GAGGACTCTG GACCCCAGGC CATACCAGGT GCTAGGGTGC CTGCTCTCCT TGCCCTGGGC CAGCCCAGGA TTGTACGTGG GAGAGGCAGA AAGGGTAGGT TCAGTAATCA TTTCTGATGA TTTGCTGGAG TGCTGGCTCC ACGCCCTGGG GAGTGAGCTT GGTGCGGTAG GTGCTGGCCT CAAACAGCCA CGAGGTGGTA GCTCTGAGCC CTCCTTCTTG CCCTGAGCTT TCCGGGGAGG AGCCTGGAGT GTAATTACCT GTCATCTGGG CCACCAGCTC CACTGGCCCC CGTTGCCGGG CCTGGACTGT CCTAGGTGAC CCCATCTCTG 55 CTGCTTCTGG GCCTGATGGA GAGGAGAACA CTAGACATGC CAACTCGGGA GCATTCTGCC TGCCTGGGAA CGGGGTGGAC GAGGGAGTGT CTGTAAGGAC TCAGTGTTGA CTGTAGGCGC CCCTGGGGTG GGTTTAGCAG WO 00/62736 PCT/USOO/08020 25 GCTGCAGCAG GCAGAGGAGG AGTACCCCCC TGAGAGCATG TGGGGGAAGG CCTTGCTGTC ATGTGAATCC CTCAATACCC CTAGTATCTG GCTGGGTT CAGGGGCTTT GGAAGCTCTG TTGCAGGTGT CCGGGGGTCT AGGACTTTAG GGATCTGGGA TCTGGGGAAG GACCAACCCA TGCCCTGCCA AGCCTGGAGC CCCTGTGTTG GGGGGCAAGG TGGGGGAGCC TGGAGCCCCT GTGTGGGAGG GCGAGGCGGG GGAGCCTGGA GCCCCTGTGT 5 GGGAGGGCGA GGCGGGGGAT CCTGGAGCCC CTGTGTCGGG GGGCGAGGGA GGGGAGGTGG CCGTCGGTTG ACCTTCTGAA CATGAGTGTC AACTCCAGGA CTTGCTTCCA AGCCCTTCCC TCTGTTGGAA ATTGGGTGTG CCCTGGCTCC CAAGGGAGGC CCATGTGACT AATAAAAAAC TGTGAACCCT CGCATTTGTG TTTTAATAAA AGAATCTGGA AGATAAATAG TCTTGAAGAG AGACAAAGGA AGGAAAATTT AAATCCTTAG ATTCAAGCAG AAGAATTCCA TGTGGAAGGT TTGGGTTGTT GTTGTTGTTG TTTGGTGTGT TTTTGTT TTTGTTTT 10 TGTTTTT TGAGATGGAG TCTCGCTGTG TTACCGGGAG CGACAGAGCC GCACGGCCGA GTCGAGTCCC AGCCAGCTAC CATCCCTCTG GAGCTTACCG GCCGGCCTTG GCTTCCCCAG GAATCCCTGG AGCTAGCGGC TGCTGAAGGC GTCGAGGTGT GGGGGCACTT GGACAGAACA GTCAGGCAGC CGGGAGCTCT GCCAGCTTTG GTGACCTTGG GTGCTTGCCT CGTGCCCCTT GGTGCCCGTC TGCTGATGTG CCCAGCCTGT GCCCGCCATG CCGCCCTCCA TCTCAGCTTT CCAGGCCGCC TACATCGGCA TCGAGGTGCT CATCGCCCTG GTCTCTGTGC 15 CCGGGAACGT GCTGGTGATC TGGGCGGTGA AGGTGAACCA GGCGCTGCGG GATGCCACCT TCTGCTTCAT CGTGTCGCTG GCGGTGGCTG ATGTGGCCGT GGGTGCCCTG GTCATCCCCC TCGCCATCCT CATCAACATT GGGCCACAGA CCTACTTCCA CACCTGCCTC ATGGTTGCCT GTCCGGTCCT CATCCTCACC CAGAGCTCCA TCCTGGCCCT GCTGGCAATT GCTGTGGACC GCTACCTCCG GGTCAAGATC CCTCTCCGGT ACAAGATGGT GGTGACCCCC CGGAGGGCGG CGGTGGCCAT AGCCGGCTGC TGGATCCTCT CCTTCGTGGT GGGACTGACC 20 CCTATGTG GCTGGAACAA TCTGAGTGCG GTGGAGCGGG CCTGGGCAGC CAACGGCAGC ATGGGGGAGC CCGTGATCAA GTGCGAGTTC GAGAAGGTCA TCAGCATGGA GTACATGGTC TACTTCAACT TCTTTGTGTG GGTGCTGCCC CCGCTTCTCC TCATGGTCCT CATCTACCTG GAGGTCTTCT ACCTAATCCG CAAGCAGCTC AACAAGAAGG TGTCGGCCTC CTCCGGCGAC CCGCAGAAGT ACTATGGGAA GGAGCTGAAG ATCGCCAAGT CGCTGGCCCT CATCCTCTTC CTCTTTGCCC TCAGCTGGCT GCCTTTGCAC ATCCTCAACT GCATCACCCT 25 CTTCTGCCCG TCCTGCCACA AGCCCAGCAT CCTTACCTAC ATTGCCATCT TCCTCACGCA CGGCAACTCG GCCATGAACC CCATTGTCTA TGCCTTCCGC ATCCAGAAGT TCCGCGTCAC CTTCCTTAAG ATTTGGAATG ACCATTTCCG CTGCCAGCCT GCACCTCCCA TTGACGAGGA TCTCCCAGAA GAGAGGCCTG ATGACTAGAC CCCGCCTTCC GCTCCCACCG CCCACATCCA GTGGGGTCTC AGTCCAGTCC TCACATGCCC GCTGTCCCAG GGGTCTCCCT GAGCCTGCCC CAGCTGGGCT GTTGGCTGGG GGCATGGGGG AGGCTCTGAA GAGATACCCA 30 CAGAGTGTGG TCCCTCCACT AGGAGTTAAC TACCCTACAC CTCTGGGCCC TGCAGGAGGC CTGGGAGGGC AAGGGTCCTA CGGAGGGACC AGGTGTCTAG AGGCAACAGT GTTCTGAGCC CCCACCTGCC TGACCATCCC ATGAGCAGTC CAGAGCTTCA GGGCTGGGCA GGTCCTGGGG AGGCTGAGAC TGCAGAGGAG CCACCTGGGC TGGGAGAAGG TGCTTGGGCT TCTGCGGTGA GGCAGGGGAG TCTGCTTGTC TTAGATGTFG GTGGTGCAGC CCCAGGACCA AGCTTAAGGA GAGGAGAGCA TCTGCTCTGA GACGGATGGA AGGAGAGAGG TTGAGGATGC 35 ACTGGCCTGT TCTGTAGGAG AGACTGGCCA GA CCCAGCCCCG AGGCTCAGAA GCGGCAGGCG GAGGCGCGGT CCGGGCGCTA TGGCCATGCC CGGCGGGTCT CACGCGGCTG CCCCTCGCCC GGCGCGCCTT CGGTAGGGGG CGCCCGGGGC CCAGCTGGCC CGGCCATGCT GCTGGAGACA CAGGACGCGC TGTACGTGGC GCTGGAGCTG GTCATCGCCG CGCTTCGGT GGCGGGCAAC GTGCTGGTGT GCGCCGCGGT GGGCACGGCG AACACTCTGC AGACGCCCAC CAACTACTTC CTGGTGTCCC TGGCTGCGGC CGACGTGGCC GTGGGGCTCT 40 TCGCCATCCC CTTTGCCATC ACCATCAGCC TGGGCTTCTG CACTGACTTC TACGGCTGCC TCTTCCTCGC CTGCTTCGTG CTGGTGCTCA CGCAGAGCTC CATCTTCAGC CTrCTGGCCG TGGCAGTCGA CAGATACCTG GCCATCTGTG TCCCGCTCAG GTATAAAAGT TTGGTCACGG GGACCCGAGC AAGAGGGGTC ATTGCTGTCC TCTGGGTCCT TGCCTTTGGC ATCGGATTGA CTCCATTCCT GGGGTGGAAC AGTAAAGACA GTGCCACCAA CAACTGCACA GAACCCTGGG ATGGAACCAC GAATGAAAGC TGCTGCCTTG TGAAGTGTCT CTTITGAGAAT 45 GTGGTCCCCA TGAGCTACAT GGTATATTTC AATTTCTG GGTGTGTTCT GCCCCCACTG CTTATAATGC TGGTGATCTA CATTAAGATC TTCCTGGTGG CCTGCAGGCA GCTTCAGCGC ACTGAGCTGA TGGACCACTC GAGGACCACC CTCCAGCGGG AGATCCATGC AGCCAAGTCA CTGGCCATGA TTGTGGGGAT TTTGCCCTG TGCTGGTTAC CTGTGCATGC TGTTAACTGT GTCACTCTTT TCCAGCCAGC TCAGGGTAAA AATAAGCCCA AGTGGGCAAT GAATATGGCC ATTCTTCTGT CACATGCCAA TTCAGTTGTC AATCCCATTG TCTATGCTrA 50 CCGGAACCGA GACTTCCGCT ACACTTTCA CAAAATTATC TCCAGGTATC TTCTCTGCCA AGCAGATGTC AAGAGTGGGA ATGGTCAGGC TGGGGTACAG CCTGCTCTCG GTGTGGGCCT ATGATCTAGG CTCTCGCCTC TTCCAGGAGA AGATACAAAT CCACAAGAAA CAAAGAGGAC ACGGCTGGT[ TTCATTGTGA AAGATAGCTA CACCTCACAA GGAAATGGAC TGCCTCTCTT GAGCACTTCC CTGGAGCTAC CACGTATCTA GCTAATATGT ATGTGTCAGT AGTAGCACCA AGGATTGACA AATATATTTA TGATCTATTC AGCTGCTTTT ACTGTGTGGA 55 TTATGCCAAC AGCTTGAATG GATTCTAACA GACTCTTTTG TTTTAAAAG TCTGCCTTGT TTATGGTGGA AAATTACTGA AACTATTTTA CTGTGAAACA GTGTGAACTA TTATAATGCA AATACTTTTT AACTTAGAGG WO 00/62736 PCT/US00/08020 26 CAATGGAAAA ATAAAAGTTG ACTGTACTAA AAATGTATAC TTGTTGCCAG GAAGGTGACC TCAAAAATTA AAAGTATAAT TATTCGGCCG GGCATGGTGG CTCACACCTG TAATTCCAGC ACTTTGGGAG GCCAAGGCAG GCGGATCACG AGGTCAGGAG TTCAAAACCA GCCTGTCCAA TATAGTG GGGCAATTTG TTAGTTATCC GCCGCCACCA AGACGCGGCA CGGCGCCTGG ACCGGAGGGG CCCCGCGCGG GCGCGAACTT TGGGCTCGGG 5 CGAGTGGGTG GTGCTCCGCC CAGCCCGAGA CGGGCGGGCG CGCGGGCCAA TGGGTGCCGC CTCTTGGCCG CGGGGGGCCC CGACCCGTGG GTCCCGGCCA CCAGCGCCCC AGCCCCGAGG CTCAGAAGCG GCAGGCGGAG GCGCGGTCCG GGCGCTATGG CCATGCCCGG CGGGTCTCAC GCGGCTGCCC CTCGCCCGGC GCGCCTTCGG TAGGGGGCGC CCGGGGCCCA GCTGGCCCGG CCATGCTGCT GGAGACACAG GACGCGCTGT ACGTGGCGCT GGAGCTGGTC ATCGCCGCGC TTTCGGTGGC GGGCAACGTG CTGGTGTGCG CCGCGGTGGG CACGGCGAAC 10 ACTCTGCAGA CGCCCACCAA CTACTTCCTG GTGTCCCTGG CTGCGGCCGA CGTGGCCGTG GGGCTCTTCG CCATCCCCTT TGCCATCACC ATCAGCCTGG GCTTCTGCAC TGACTTCTAC GGCTGCCTCT TCCTCGCCTG CTTCGTGCTG GTGCTCACGC AGAGCTCCAT CTTCAGCCTT CTGGCCGTGG CAGTCGACAG ATACCTGGCC ATCTGTGTCC CGCTCAGGTA TAAAAGTTTG GTCACGGGGA CCCGAGCAAG AGGGGTCATT GCTGTCCTCT GGGTCCTTGC CTTTGGCATC GGATTGACTC CATTCCTGGG GTGGAACAGT AAAGACAGTG CCACCAACAA 15 CTGCACAGAA CCCTGGGATG GAACCACGAA TGAAAGCTGC TGCCTTGTGA AGTGTCTCTT TGAGAATGTG GTCCCCATGA GCTACATGGT ATATTTCAAT TTCTTTGGGT GTGTTCTGCC CCCACTGCTT ATAATGCTGG TGATCTACAT TAAGATCTTC CTGGTGGCCT GCAGGCAGCT TCAGCGCACT GAGCTGATGG ACCACTCGAG GACCACCCTC CAGCGGGAGA TCCATGCAGC CAAGTCACTG GCCATGATTG TGGGGATT TGCCCTGTGC TGGTTACCTG TGCATGCTGT TAACTGTGTC ACTCT'TCC AGCCAGCTCA GGGTAAAAAT AAGCCCAAGT 20 GGGCAATGAA TATGGCCATT CTTCTGTCAC ATGCCAATTC AGTTGTCAAT CCCATTGTCT ATGCTTACCG GAACCGAGAC TTCCGCTACA CTTCACAA AATTATCTCC AGGTATCTTC TCTGCCAAGC AGATGTCAAG AGTGGGAATG GTCAGGCTGG GGTACAGCCT GCTCTCGGTG TGGGCCTATG ATCTAGGCTC TCGCCTCTTC CAGGAGAAGA TACAAATCCA CAAGAAACAA AGAGGACACG GCTGGTTC ATTGTGAAAG ATAGCTACAC CTCACAAGGA AATGGACTGC CTCTCTTGAG CACTTCCCTG GAGCTACCAC GTATCTAGCT AATATGTATG 25 TGTCAGTAGT AGGCTCCAAG GATTGACAAA TATATATG ATCTATTCAG CTGCTTTTAC TGTGTGGATT ATGCCAACAG CTTGAATGGA TTCTAACAGA CTCTTGTT TTTAAAAGTC TGCCTTGTTT ATGGTGGAAA ATTACTGAAA CTATTTACT GTGAAACAGT GTGAACTATT ATAATGCAAA TACTTTTTAA CTTAGAGGCA ATGGAAAAAT AAAAGTTGAC TGTACTAAAA ATG GAATTCCCAG ATGGGCAGAG GTGGCTGGGC TGGTGACCCT AAGTGTGTCT CCTGCCTTTA TTCTCTCTAG TGGGTTATTC TTTCATGTGG TATCTTGCCT 30 ACAGCATGCT GTGTTTGGAC ACAAACCCCT TTCCTTGGTT TCTCTGACCC AGCTGAGATG GACTGATTCC AAAAGAACTC ACCTATGTAC TGGGGTAGGG GAGGGAGGGT TTGCAGT ATTAACTAA GGTTCAAAGA GTGCTATATA GTGAGAAAGG CTTCTTTTTT TTTTTTTT TTTTTTGGCA GAGTGCTGCC TCCTAGAAAT TTCTCTrGGT AACTTCCTTC TCTGAAGCAC AGATAAAGAA AACAATTACA GTAGAAACAT TTATGAGGGA CACATTGGAG GCCGATGAAG CTTTTCAAGT TCCAGCAGTG CAGGGATGTG GGCAGAACTG ACATTGGAAA 35 ATACTAGAAT GATGGAAATT CAGTTGGAGA GGACTGCCCT TTAATGTC TGGGGAGTCT GCTCAGGGAG AAATGACAAG TCTGGCGGGG ACAAGTATGG GATTTGGTAA GACTTGGATC AACTTGGGAT ACAGGGTGGG GGTCGGGAGT GGAATCAATG AATGATGCCA GAGCAGATCA ACTAACAAGA GGACCCTGAT GAGCCCCAGG CAGAGGCGTC TCCCTTATGC CCCACTCTGA AGTGTTTGTT AGTAAACACC AGAACGCCAT TGTTGTTACT GCTGAATTTT ATTTTGGGCT GTACATATTT AGATGCTTAA GGTAAAAATG ATAAAGCCCT CAAGCCACTG 40 TGTGGGTTTG GGTCCAAGTG TTCCTTCTTG CTGCCTCTCT AACACGCCTG GTTAAAATAA TCCCTTTGGA TGGTGCTGAG AAGCACCTGA ACCAAGTGGG TCCCCAAATA ACAATGGCGT GCAAGTGTCT GGTTCCCAGA AGTTGGTGAC TAGGTAAGCA GCTTCAGGGA GAGGGGGCTG ATTCCCAGAC AGTCGCCTGT TCCTGCGGGG ATGGGGCTGA GGCTTGGGGA ATGTGGGCAG GAGGATATGC CATTTGATTC TGTTGCACAC GTTCTTTTCC CTTCTTTCTG TATGTCTGGT CATTCTGCTA TTCTGTCGTT CCTCACATAG GTTGGACATT GGCCGGCTGC 45 CAGCATAAGT GCCAGTGTGA TTGCTAGG TGTGAGCTGA GAAAGAGAGG TGGAGGCTAA GCAGGTGTGA TGCTTCTCAG AGGTGCTGAG TTTGCCCT TCTGAGCAGG GAATCTTGC TTATCCCTTT GACCAAGGAT CTTTGCTGCA AAGGCTGGGT ATCGGCTGTG CTCAGCAAAG CGTCAACTCG TGCAAGAACT TAGCAGGAAT AGTTCTGGCT AAGGTTAGGA GGCTGCCACC AAAGTCTCTT TTTTGTTCCT CTGCTTCTCC CGTTTGCCTC CTTATCATGA GATCTTTTTG CTAAGCTGGC AGAAAGAT7G CATAGTCAGT GCTTCCAGCT CTGCTCCCAC 50 CTGATCCTGC ACTGTCCTCT GGTCCCTGAA TGAATGAACT CTGATACCCA ATCTTGTCTC GAGCCTTCTC TATGCCACTC ATGGCTCCTC TTCTGCTCTT TCCATCTTT TGCTGAGAGT TCTGAGCTCT GTACTTCCTC TTGGCCCATC TCACTTCCTG AAACACCCCT GAAGAGGGTT GCTTATCTTG ATGGAACTCA AAAAGCCAAA AAGCTGCAGG CAGAGGCGTT GAGGACATCT GTTTGGGGAA CTAAGAGCAG CAGCACTTTC AGATTCAGTC CATATAGAGC TGTCCTACAG CATTCTGGAA ACTTGAGGAT GTGCGGTGCA TAAAGGGGCT GGAAGTGACC 55 CACCTGTGAT GAGCCCTTrC TAAGGAGAAG GGTTTCCAAG AGATCACCCC ACCAGAAAAG GGTAGGAATG AGCAAGTTGG GAATTTTAGA CTGTCACTGC ACATGGACCT CTGGGAAGAC GTCTGGCGAG AGCTAGGCCC WO 00/62736 PCT/USOO/08020 27 ACTGGCCCTA CAGACGGATC TTGCTGGCTC ACCTGTCCCT GTGGAGGTTC CCCTGGGAAG GCAAGATGCC CAACAACAGC ACTGCTCTGT CATTGGCCAA TGTTACCTAC ATCACCATGG AAATTTTCAT TGGACTCTGC GCCATAGTGG GCAACGTGCT GGTCATCTGC GTGGTCAAGC TGAACCCCAG CCTGCAGACC ACCACCTTCT ATTTCATTGT CTCTCTAGCC CTGGCTGACA TTGCTGTrGG GGTGCTGGTC ATGCCTTTGG CCATTGTTGT 5 CAGCCTGGGC ATCACAATCC ACTTCTACAG CTGCCTTT ATGACTTGCC TACTGCTTAT CTTTACCCAC GCCTCCATCA TGTCCTTGCT GGCCATCGCT GTGGACCGAT ACTTGCGGGT CAAGCTTACC GTCAGGTAGC CTGCGGCGTG GGGTGGGCAG CAATTGAGGC AGCTGGGAAA TGAGGCTACA AAGCCAGAGCS CTGCTGAATT TTATTTTGGA CTGTACATAT TTAGATGCTT AAGGTAAAAA TGATAAAGCC CTCAAGCCAC TGTGTGGGTT GGGTCCAAGT GTTCCTTGCT GCTGCCTCTC TAACACGCCT GGTTAAAATA ATCCCTTTGG ATGGTGCTGA 10 GAAGCACCTG AACCAAGTGG GTCCCCAAAT AACTATGGCG TGCAAGTGTC TGGTTCCCAG AAGTTGGTGA CTAGGTAAGC GACTCAGGGA GAGGGGCTGA TTCCCAGACA GTCGCCTGTT CCTGCTGGGA TGGGGCTGAG GCTTGGGGAA TGTGGGCAGG AGGATATGCC ATTTGATTCT GTTGCACACG TTCTTTTCCC TTCTTTCTGT ATGTCTGGTC ATTCTGCTAT TCTGTCGTTC CTCACATAGG TTGGACATTG GCCGGCTGCC AGCATAAGTG CCAGTGTGAT TTTGCTAGGG TGTGAGCTGA GAAAGAGAGG TGGAGGCTAA GCAGGTGTGA TGCTTCTCAG 15 AGGTGCTGAG TTTTTGCCCT TCTGAGCAGG GAATCTTTGC TTATCCCTTT GACCAAGGAT CTTTGCTCCA AAGGCTGGGT ATCGGCTGTG CTCAGCAAAG CGTCAACTCG TGCAAGAACT TAGCAGGAAT AGTTCTGGCT AAGGTTAGGA GGCTGCCACC AAAGTCTCTT TTGTTCCT CTGCTTCTCC CGTTGCCTC CTTATCATGA GATCTTTG CTAAGCTGGC AGAAAGATTG CATAATCAGT GCTTCCAGCT CCGCTCCCAC CTGATCCTGC ACTGTCCTCT GGTCCCTGAA TGAATGAACT CTGATACCCA ATCTTGTCTC GAGCCTTCTC TATGCCACTC 20 ATGGCTCCTC TTCTGCTCTT TCCATCTT TGCTGAGAGT TACTGAGCTC TGTACTTCCT CTTGGCCCAT CTCAC'TCCT GAAACACCCC TGAAGAGGGT TGCTATCTT GATGGAACTC AAAAAGCCAA AAAGCTGCAG GCAGAGGCGT TGAGGACATC TGTTTGGGGA ACTAAGAGCA GCAGCACT CAGATTCAGT CCATATAGAG CTGTCCTACA GCATTCTGGA AACTTGAGGA TGTGCGGTGC ATAAAGGGGC TGGAAGTGAC CCACCTGTGA TGAGCCCTTT CTAAGGAGAA GGGTTTCCAA GAGATCACCC CACCAGAAAA GGGTAGGAAT GAGCAAGTTG 25 GGAATTTTAG ACTGTCACTG CACATGGACC TCTGGGAAGA CGTCTGGCGA GAGCTAGGCC CACTGGCCCT ACAGACGGAT CTTGCTGGCT CACCTGTCCC TGTGGAGGTT CCCCTGGGAA GGCAAGATGC CCAACAACAG CACTGCTCTG CGAATTCGGG GGACATCTGT TTGGGGAACT AAGAGCAGCA GCACTTTCAG ATTCAGTCCA TATAGAGCTG TCCTACAGCA TTCTGGAAAC TTGAGGATGT GCGGTGCATA AACGGGCTGG AAGTGACCCA CCTGTGATGA GCCCTTCTA AGGAGAAGGG TTTCCAAGAG ATCACCCCAC CAGAAAAGGG TAGGAATGAG 30 CAAGTTGGGA ATTTTAGACT GTCACTGCAC ATGGACCTCT GGGAAGACGT CTGGCGAGAG CTAGGCCCAC TGGCCCTACA GACGGATCTT GCTGGCTCAC CTGTCCCTGT GGAGGTTCCC CTGGGAAGGC AAGATGCCCA ACAACAGCAC TGCTCTGTCA TTGGCCAATG TTACCTACAT CACCATGGAA ATTTTCATTG GACTCTGCGC CATAGTGGGC AACGTGCTGG TCATCTGCGT GGTCAAGCTG AACCCCAGCC TGCAGACCAC CACCTTCTAT TTCATTGTCT CTCTAGCCCT GGCTGACATT GCTGTTGGGG TGCTGGTCAT GCCTTTGGCC ATTGTTGTCA 35 GCCTGGGCAT CACAATCCAC TTCTACAGCT GCCTTTTTAT GACTTGCCTA CTGCTTATCT TTACCCACGC CTCCATCATG TCCTTGCTGG CCATCGCTGT GGACCGATAC TTGCGGGTCA AGCTTACCGT CAGATACAAG AGGGTCACCA CTCACAGAAG AATATGGCTG GCCCTGGGCC TTTGCTGGCT GGTGTCATTC CTGGTGGGAT TGACCCCCAT GTTTGGCTGG AACATGAAAC TGACCTCAGA GTACCACAGA AATGTCACCT TCCTTTCATG CCAATTTGTT TCCGTCATGA GGATGGACTA CATGGTATAC TTCAGCTTCC TCACCTGGAT TTTCATCCCC 40 CTGGTTGTCA TGTGCGCCAT CTATCTTGAC ATCTTTTACA TCATTCGGAA CAAACTCAGT CTGAACTrAT CTAACTCCAA AGAGACAGGT GCATTTATG GACGGGAGTT CAAGACGGCT AAGTCCTTGT TTCTGGTTCT TTTCTTGTTT GCTCTGTCAT GGCTGCCTTT ATCTCTCATC AACTGCATCA TCTACTTrAA TGGTGAGGTA CCACAGCTTG TGCTGTACAT GGGCATCCTG CTGTCCCATG CCAACTCCAT GATGAACCCT ATCGTCTATG CCTATAAAAT AAAGAAGTTC AAGGAAACCT ACCTTGAT CCTCAAAGCC TGTGTGGTCT GCCATCCCTC 45 TGATTCTTTG GACACAAGCA TTGAGAAGAA TTCTGAGTAG TTATCCATCA GAGATGACTC TGTCTCATrG ACCTTCAGAT TCCCCATCAA CAAACACTTG AGGGCCTGTA TGCCTGGGCC AAGGGATTTT TACATCCTTG ATTACTTCCA CTGAGGTGGG AGCATCTCCA GTGCTCCCCA ATTATATCTC CCCCACTCCA CTACTCTCTT CCTCCACTTC ATTTTTCCTT TGTCCTTTCT CTCTAATTCA GTGTTTTGGA GGCCTGACTT GGGGACAACG TATTATTGAT ATTATTGTCT GTTTTCCTTC TTCCCAATAG AAGAATAAGT CATGGAGCCT GAAGGGTGCC 50 TAGTTGACTT ACTGACAAAA GGCTCTAGTT GGGCTGAACA TGTGTGTGGT GGTGACTCAT TTCCATGCCA TTGTGGAATT GAGCAGAGAA CCTGCTCTCG GAGGATGCCT AGGAGATGTT GGGAACAGAA GAAATAAACT GAGTAAGG GGGACTTAAA CTGCTGAATT C AAATGATAGA CCGTCAATAA TITTGTTAAAT GCTTTTTAAA ATGAATGCTT TAAGCCGGGT GCAGTGCCTC ACATCTGTAA TCCCAGCACT TITGGAGCCGA GCGGGTGGAT TGTGTGAGGT CAGGAGTTCG AGACCAACCT GGCCAACATG GCAAAACCTC ACTCTCTACC AAAAATACAA 55 AAATTAGCCA GGCATGGTGG CAGGCACCTG TGATCCCAGC TACTCAGGAG GCTGAGACAG GAGAATCGCT TGAACCCGGG AGGCAAGGTT GCAGTGAGCC AAGATTACGC CATTGTACTC CAGCCTGGGT GACAGAGAGA WO 00/62736 PCT/USOO/08020 28 GACTCCGTCT CAAAAAAAAA AAAAAAAAAA AAAAAATTAC GCTTCAAACA CATGATCTCT CACCACTGrT GAATCTT TCTATGAGCC CAGGAGGGCC TCTCAGAGAG GAAAGCTCCT AGGTCTTCCT I1CCCTCTGC AAACTCCCTG CCTTGAAGGT TCAGAAGGAC TGTGCGTGCT CGTTGCATCC 'ITTGCAAGTG TCCAAACCCT GATCCCAGCT GTGC'ITAGGG GTTCCTGCAA ACCTITCCA GGTGT-FAATT ACCTCCCACT TCATJTCCTG 5 TIACCAACT CAGCTr'TI7G T'TrAGTGTG TTTGAATTCC CTGAACTGAC CGTTGTCTGA TCTCCACCTC CCAACTGAAT TAGGGGAGCT GGGCTTCTGG AAACCCAGGT GCCGGGTGTT GCAGAGTGGC TGAAAGCTGG GATGTGGCAG ATCCGTGGCT ACATTCATGC ACACACACAC ACCCACATAC CCACACATGC ACACACACAC ACACACCCGC ACTCACACAC TTGGACATGC ATAGACCACA GCITCCACA CCCTTCCTAG ACAGGGGTCA CTTGGTATCC TGGAGAGAGT GTGAAGTCCT GGAATGGAAA GAGGGGGGAT TAAGCCCCAC CTCTAGCCAT 10 GGGACTGAGA CAAGTCACCA CCAACCCATC TGCGCCTTGT TTACCTCCTC TGTGAGGCAA GCACAGAGCC CATGCCTGCC CCCCTGGATG GGAGTGATGT GAAACT7GAA GGGCGGTCAG AGCAAGGGTC GGGAATGGAA GGCCCTTGGG AAAAAAGGCC CTI1?CAACTA GGGGCACAGA GGAGGCCCTG GGCTGAGAAC YTGACAGCAC CTI7GTAATI7G GTAAGCCAAG CCCGAAGGGA CTGGAAATAC TCAGATGTGT CTGTCTCCCT TATTAGGTTC AAAGTCCCTC AAGACCCTGT CTCCATCACA GTGCTCCAGT CCAGACCCCT CCTCTGAGCT CCAGACCCTG 15 CTGGACCCAA CCAGCCCTAT GGGGTCGCAT CCCCACCTGC CTGGAATTCT CCAAAGAACC TCCCCTI1AA CAGTICCAGC C'ITTAACAGT TCCAGTCTAA ACACATGACC TrTCTCCTCT AAATCAGCCC CCCATCTCTG CC'ITTGCAGG AGATGGAAGC CATGACACCT GCCTCGCCCC TGTCCTCACC CCATCCATGT CCAATCAAGC ACTAGGCATG TCAGG'ITTAC CCTCTAAACT CCTCTGGAAT CCAGTCTCTC AGTCTCCATC ATCCCAGGTC GAAGCTAATG GGCTAACTGG TCCTTGCTTC CACTCTACCC CCACTGCAGT CCTGACYTCC TGAGCAGCAG 20 CCAGGGCCTA ATCGATATL1C ACACCAAGCG CCAACCTGAC TGAGATATCC TCCTGCACCA TCATCCCTCC ACCCTGTTTA GYITCTGCTCA CCCTCAGTGT TCTCATCAAT AATCCACTCC CCTCACAGGC GCGTITGGGA CCCCATGTTC TATGCTCTCA CAGGACC'= TGCTlGAT1T 'ITCACTGTAC ITAGGTCAGT TTGCAGTTAT TAAGTGACTG AGCAATGTCT GGC'ITCTCCA GTAGACTGTC AGCTCCTAGC CATTGTATAC CTAGCACCGC TGTGTGGGAG CACGTGACAA ACGTCCAGTG AGTCAGGGAC TCAGCAGTCT CCAYITCTCC GCCCTGCTGG 25 AGAATGCGTG TA ITGGCAA TCCCCAGCCC CTGTGCCATC TAACCATCTT TTCTTCTCTG TTCAGCCCAG GTGTGGCCTC ACTCACATCC CACTCTGAGT CCAAATGTFC TCTCCCTGGA AGATATCAAT GTTTCTGTCT GITCGTGAGG ACTCCGTGCC CACCACGGCC TUITrCAGGT GAGTCAAAGG GATTCCTCAG YI7CACTAGTT AGGGGAGGTG GGCAGACACC CTGGAGAACT CCCTGGAAAG CTCAACTCTC ATGCCCCGGA CAACAGTTGA AGGAACCATG GTGATGTTAA GCCCAAAGAC AAAACCTCTC AGGTGTCCAA GTCCCTG11G GAATC'ITGGG 30 AGCAGAGGGA ATG117CTGTG GTCTAGAGGA AGAGGGGCTC AGGGAGGAGA AGGGCACAYT CCTGGFTGTIT ATATG'TTTCT ATCTATCCCA GATGAACTTG GAAGTGAAGG GAAGAGAGT7 AAACATTAAA GTAAATACCC AGTGGATCAG ACAGCAATGT GCCAGATTGC CTTGGAAACA AAATATCTCC AACACATGGC TGACATTffGG TGGGAGATCA GAACACCCTA AAGAGAGAAT YFAAGGGGAG GGGGAGGAGG ACCTGAGCCA GAGTAGAAGC AGAGGATAGG GAGATCTGT-T CTTGGGGACA GCATrGCAA GAAACAAGGC TGAGGGGTCC ACTCCAACCT 35 CTCCACCCTG CTGCAGGTGC TGCCTATGAT GAAGATGAGC AGATGGCCAT CTCAGCTGGG GCCACAGTGC ACTGGACCTA TAGYI17CCAA TTCCGCACTC AGCAGGCATC 'ITTCTGATGA TCCGATGGCT TCTCAGAGCC AGGGATGGGC CAGGATCCAT CCCC'I1rGGCT ACTGTCYrGC TGAGAAATTT ATAAGCAGCA TCTGGTGCTA TAC TJ7GGTC TCTAGTGAGT TAGCTCATGA AAGATGATAG ACTCTCCAAG CCAGGGGTAT GCAGGAAATG GGTTTTCTGT AGCTACAGAA ATGGGGTTGA GGGTTGGACC AAGGGACTAC CCAGGGGAAG TCTTACCTTC 40 AGAGGACTCT GGAAAGGAGG CTGCAAGT TCATGGGTCA AGAATTCAGA GCCCAGTAGA GACAGCTTAT CTCTGT7CCA AGATGTCTGG GGCCTrGGTT GGAAGATTCA AAGGCTAGGA AACCAGGAGC CACCAAAAGC GTAACTGGGG CCAGAGGATC CACTTTCAAG GTGGCAAGTT GGTTCCCCCC ATGTGGCTGC TTGAGTATCC TCACATGGCG GCTCACATCC TTCCAAGTAA GCAATGCAAA AGGCCAAGAA AGATGCTGCA AAGATGTITAT GACCTAGCCT CAGAAATCAC ACACCATCCC TGCCACCATT AGTAAGAAGT CCAGCCCACG TCCAGGAGAA 45 GAGGAAGCAG A'rFCCTCCTT TTGAAATGAA GAATATCAAG TAATTCGGGG GGCATATGAA AGCCACCACA CACCACAGOG ATCT1TAG AGCATACITC TI'ATACCATC ACTGTAGTTC CTTAAGACTC AGGGGCAAAG CCTCACYI'CC TTAGCACCCA GTGAAGACCA CGCTTACTCC CTCACTCAAC CTCTTGCTAC TTCCCACCTC TCCTGTCCAA CATCTAGTGT CACTTCCAG AACATACCAA CAGCTTCCCC AGTrCTGTGC CTCTGCTCAG GCTG'VrCCCC CTGCCTGGTC CAC'ITGTCCT CCTTC'TFGTC CGGTCAAAAT GCTTCTTATC CTTCAAGACC 50 CAGCTCTAGA GTCACCTCCA ACCCCTI'ACC CACCAGCCCC CTCTCCAAGT CTGTGTCCCA CAACCCCCCT GCTCCCTCCA GGGCACCCTC CACCCTCTGG GCCACAGTrG TCAGGAGTCA GGCAGGGCAG GGGCCGGGTG GTGTCT7CTT TGTGTTCTTG CACTCAGGGC AGAGCTCAGC ACAGAGCAGA CGCTCAAAAA ACA'ITTAAAG GATAGAAGCA TrGATTTGTG GGTCCCCCAG TCTGGCTCCA GGATGCCAGC CAGCTGCTCC TAGAAGCAAA CGGACTITTC CTGGGAAATC CCAGAGGTGA TGATCAGTAA TCTCTCCCGT GACTCGTAGT TCAGCTCTTC 55 CTCCATGAGC CTGACTATCA GTGGACCT7C CAGAAAGAGC CCCTF=CCT TCTCTCACCC ACAGCACAGG GCACTGGGAA AATGCCCAAT GAGTCCTGCC TCTGGGTT1GT GCTTTGGACT TITCAGTGTG TCTCGCATCC WO 00/62736 PCT/USOO/08020 29 ACTCTTCAAC TTGAATGTTG CAACAGCCAT GAAAAAAGAA ATGCAAAGCG ATTCAGGATG AGAGCAATAC CCTACTCCAA AGAAGGCAAC ATAGAAGCTC AGAGAGATCA AGCAATTrGC CCAAGACCAC ACAGCTAGGA GTGGAACTCA TGGCTGTCCA AGCCCCATGC CTCTGCTGAA GGTAGAGATG AATTACAGCA ACAAGTCTAG AAAGGTGCCT GCCCTATGGT CTGTGAGTCT TGCCTAAGAA TGAAAGAGGA GCCAGTGGGT TAAAGATGAG 5 GTCACCAACA ACGGTGGTGT TGGAGTTAC CACTGATAAT AAGGGTGCAA AATGTAAATT ACTAATGTTT ATTGAGCCTA GTGCAGTGCG TGGGGCATTT TGCACATTGT CTCTGATCCC TATGACAACC CTGAGAGGTA GTGGTTTTAA CTGCCATGTT ACAGGTGAGG TCATTGTGGT TCAAGGACGT TAAGTAACTT CCCCAGCGTG ACACGGCTTA TAAGTAAGGC AGCCAGGATG TGAACCCAGT AGGACTATCT GGCTGCAAAG TCCCCACCCC CCTCGCCATC TGTATCCTCC AATCACTTCA GTGCTTTGCT GCATAGAAGG TAACGGAAAT CACGATGCCA 10 CAGACTGTCC AGGAAGACAG AAACTAGGCA GATGGGCTGG CCATGGTCTC CAAGCCAGAC TGGAATCTCC AGGTCTGGAA TGATATCATT TTTCTCTT AATAAATTAA CTCACCCACC ACACGGCTTT GAGAGGCTCA AAGTTGACCA ACTCCCTTGG GAGGGCCCCG GTTGATAAGG AAGGAACGTG AATCCTCCCA TCACGGAAGC TTCAAGGAGG TCAAGGGTCC AACACTTGAG ATTGTTAGTG CTGTTGGTGG ATACTGGCCA AGGAAATATC CCAGTGGAGC CTCGAGATGA AGAACATGAG GCCCCCGTTT AGAACCAAGG ATCAGAGGGG GCTCTGTAAG 15 ACCCAGGGGA GTCAGGTGCA CTGGAGCGCG GGCATGCAGA AAACAGCCTG AGCTCCACCT CGGCTTCTCC TTGTCCTGGC TGGTTGTCCT TAACCCCTGT CTCCTTCTGG ACCAGTT GTCCTTCCCT TGTGACCGCT GAGGGGTAAC AGCCTCTTTC CACTTTCTTT CAGCGCCGAC ATGCTCAATG TCACCTTGCA AGGGCCCACT CTTAACGGGA CCTTTGCCCA GAGCAAATGC CCCCAAGTGG AGTGGCTGGG CTGGCTCAAC ACCATCCAGC CCCCCTTCCT CTGGGTGCTG TTCGTGCTGG CCACCCTAGA GAACATCTTT GTCCTCAGCG TCTTCTGCCT 20 GCACAAGAGC AGCTGCACGG TGGCAGAGAT CTACCTGGGG AACCTGGCCG CAGCAGACCT GATCCTGGCC TGCGGGCTGC CCTTCTGGGC CATCACCATC TCCAACAACT TCGACTGGCT CTTTGGGGAG ACGCTCTGCC GCGTGGTGAA TGCCATTATC TCCATGAACC TGTACAGCAG CATCTGTTTC CTGATGCTGG TGAGCATCGA CCGCTACCTG GCCCTGGTGA AAACCATGTC CATGGGCCGG ATGCGCGGCG TGCGCTGGGC CAAGCTCTAC AGCTTGGTGA TCTGGGGGTG TACGCTGCTC CTGAGCTCAC CCATGCTGGT GTTCCGGACC ATGAAGGAGT 25 ACAGCGATGA GGGCCACAAC GTCACCGCTT GTGTCATCAG CTACCCATCC CTCATCTGGG AAGTGTTCAC CAACATGCTC CTGAATGTCG TGGGCTFCCT GCTGCCCCTG AGTGTCATCA CCTTCTGCAC GATGCAGATC ATGCAGGTGC TGCGGAACAA CGAGATGCAG AAGTTCAAGG AGATCCAGAC GGAGAGGAGG GCCACGGTGC TAGTCCTGGT TGTGCTGCTG CTATTCATCA TCTGCTGGCT GCCCTrCCAG ATCAGCACCT TCCTGGATAC GCTGCATCGC CTCGGCATCC TCTCCAGCTG CCAGGACGAG CGCATCATCG ATGTAATCAC ACAGATCGCC 30 TCCTTCATGG CCTACAGCAA CAGCTGCCTC AACCCACTGG TGTACGTGAT CGTGGGCAAG CGCTTCCGAA AGAAGTCTTG GGAGGTGTAC CAGGGAGTGT GCCAGAAAGG GGGCTGCAGG TCAGAACCCA TTCAGATGGA GAACTCCATG GGCACACTGC GGACCTCCAT CTCCGTGGAA CGCCAGATTC ACAAACTGCA GGACTGGGCA GGGAGCAGAC AGTGAGCAAA CGCCAGCAGG GCTGCTGTGA ATTTGTGTAA GGATTGAGGG ACAGTTGCTT TTCAGCATGG GCCCAGGAAT GCCAAGGAGA CATCTATGCA CGACCTTGGG AAATGAGTTG ATGTCTCCGG 35 TAAAACACCG GAGACTAATT CCTGCCCTGC CCAATTTTGC AGGGAGCATG GCTGTGAGGA TGGGGTGAAC TCACGCACAG CCAAGGACTC CAAAATCACA ACAGCATTAC TGTTCTTATT TGCTGCCACA CCTGAGCCAG CCTGCTCCTT CCCAGGAGTG GAGGAGGCCT GGGGGCAGGG AGAGGAGTGA CTGAGCTTCC CTCCCGTGTG TTCTCCGTCC CTGCCCCAGC AAGACAACTT AGATCTCCAG GAGAACTGCC ATCCAGCT GGTGCAATGG CTGAGTGCAC AAGTGAGTTG TTGCCCTGGG TTTCTTTAAT CTATTCAGCT AGAACTTTGA AGGACAATTT 40 CTTGCATTAA TAAAGGTTAA GCCCTGAGGG GTCCCTGATA ACAACCTGGA GACCAGGATT TTATGGCTCC CCTCACTGAT GGACAAGGAG GTCTGTGCCA AAGAAGAATC CAATAAGCAC ATATTGAGCA CTTGCTGTAT ATGCAGTATT GAGCACTGTA GGCAAGAGGG AAGAAAGAGA AGGAGCCATC TCCATCTTGA AGGAACTCAA AGACTCAAGT GGGAACGACT GGGCACTGCC ACCACCAGAA AGCTGTTCGA TGAGACGGTC GAGCAGGGTG CTGTGGGTGA TATGGACAGC AGAAGGGGGA GCCAGGTTCC AGCTCACCAA TACTATTGCA CACCACCTGT 45 CCTGCCTC GCCCTTCAAA GATGAGCTGT TCCCGCCGCC ACTCCAGCTC TGGCTTCTGG GCTCCGAGGA GGGGTGGGGA CGGTGGTGAC GGTGGGGACA TCAGGCTGCC CCGCAGTACC AGGGAGCGAC TGAAGTGCCC ATGCCGCTTG CTCCGGAGAA GGTGGGTGCC GGGCAGGGGC TGCTCCAGCC GCCTCACCTC TGCTGGGAGG ACAAACTGTC CCAGCACAGA GGGAGGGAGG GAGGGCAGGC AGCGGGGAGA AGTTTCCCTG TGGTCGTGGG GAGTT GAGCTCTTCA ATATTTTAGT GAAAGCTATA GATGAGGCTC CATAGGGGAT AAAGCACAGA 50 CACACCTTTT CAGAGGGCTT GTGGACTCTG GGCAGCCTGT CCATAGACCT CTGTCCCCAA CTGGCAAGTC AGGAAACTCC AGATTAAGGA GCCCCAATGT GGTrGAACAG CCAGGTGCAC AGATGAGTCA ACCACACAGC CAGGCCAGGG AGGGCCTTCA CTCAAGAGCC TACAGCCAGT TCACAGCCAA GCCAGGGCTA GCGCCAGGCC ACCCATAAAC TGATCTGAGA CTCTGTTTCC CTGTCTCCAT GATGATGGGA TCAGGCTTGA TTGCTGGTTT GTAGGCTTGT TATGAATCAA GTCACAGGGA AGAGGAGCTG ATGGGCTGGG GGGACGTCCT CTGGCCCTCC 55 TGTCTCTTICC CCAGATCCAC TGGGCCCACT CTTATCTGTT CTCTTCTGAA GGAAGGGTTT TAAGGCTTCA AAAAAAAATG T-TGAAAGT CCCTGCCCTT TCCAGCTCCT ACCGTCTCAG CCCTGGGAGT GTAAAGTGCT WO 00/62736 PCT/USOO/08020 30 GCAGATAGTT AGTAAGTCTT TGAGCAAAAC TGAGAAAGCC AGCCTGAGCC TTGACATGGG AGAAACCTCC GCCATACATC TCCGAAGAAA CGGCCGCGTG TCTCAGGGGA GCGCAAACAC CCGTACCCAG GAAACAGGAC AGCTTCTGCC ACTGTCGCCC TTGGGAGCCG TACGTGGCAT GACAAAGAAA TCCCAGGACT CCGCCTGCCC ACCTGGCCAC CCTCTGTTTA CACCTTCCGC GTAAACGCCC ACTGTTTACA TCCAAAACTC AGACACAAAA 5 TAACCACCTC AAGAAGATAA ATAATGATAA GAAATAAATG TTACGCGAGG CAAATTTATT CACATGGGGC TTCCCAGGCC ACTTTGTGGT CAGCCGGGAG GGACGTTTT GCCGTCCCAC GACTCCAACG GGCAGCCGGG CCTACGCAAA CATGGAAATC TTCCAAGAGC CTCCCTGGCC CCCAGGGCTC AGAGGGTGGC AGAGCGGAGA GCGAAGGTGG CCGCAGCCTT CCCGGCCCCA CAGCCAGCCT GGCTCCAGCT GGGCAGGAGT GCAGAGCTCA GCTGGAGGCG AGGGGGAAGT GCCCAGGAGG CTGATGACAT CACTACCCAG CCCTTCAAAG ATGAGCTGTT 10 CCCGCCGCCA CTCCAGCTCT GGCTTCTGGG CTCCGAGGAG GGGTGGGGAC GGTGGTGACG GTGGGGACAT CAGGCTGCCC CGCAGTACCA GGGAGCGACT GAAGTGCCCA TGCCGCTTGC TCCGGAGAAG GTGGGTGCCG GGCAGGGGCT GCTCCAGCCG CCTCACCTCT GCTGGGAGGA CAAACTGTCC CAGCACAGAG GGAGGGAGGG AGGGCAGGCA GCGGGGAGAA GTTTCCCTGT GGTCGTGGGG AGTTGGGAAA AGTTCCCTTC CTTCCGGAGG GAGG CAGATTCACA AACTGCAGGA CTGGGCAGGG AGCAGACAGT GAGCAAACGC CAGCAGGGCT 15 GCTGTGAATT TGTGTAAGGA TTGAGGGACA GTTGCTTTC AGCATGGGCC CAGGAATGCC AAGGAGACAT CTATGCACGA CCTTGGGAAA TGAGTTGATG TCTCCGGTAA AACACCGGAG ACTAATTCCT GCCCTGCCCA ATTTTGCAGG GAGCATGGCT GTGAGGATGG GGTGAACTCA CGCACAGCCA AGGACTCCAA AATCACAACA GCATTACTGT TCTTATTTGC TGCCACACCT GAGCCAGCCT GCTCCTTCCC AGGAGTGGAG GAGGCCTGGG GGGAGGGAGA GGAGTGACTG AGCTTCCCTC CCGTGTGTTC TCCGTCCCTG CCCCAGCAAG ACAACTTAGA 20 TCTCCAGGAG AACTGCCATC CAGCTTTGGT GCAATGGCTG AGTGCACAAG TGAGTTGTTG CCCTGGGTTT CTTTAATCTA TTCAGCTAGA ACTTTGAAGG ACAATTTCTT GCATTAATAA AGGTTAAGCC CTGAGGGGTC CCTGATAACA ACCTGGAGAC CAGGAITTA TGGCTCCCCT CACTGATGGA CAAGGAGGTC TGTGCCAAAG AAGAATCCAA TAAGCACATA TTGAGCACTr GCTGTATATG CAGTATTGAG CACTGTAGGC AAGACCCAAG AAAGAGAAGG AGCCATCTCC ATCTTGAAGG AACTCAAAGA CTCAAGTGGG AACGACTGGG CACTGCCACC 25 ACCAGAAAGC TGTTCGACGA GACGGTCGAG CAGGGTGCTG TGGGTGATAT GGACAGCAGA AGGGGGAGAC CAAGGTTCCA GCTCAACCAA TAACTATTGC ACAACCACCT GTCCCTGCCT CAGTTCCCTT TTATGTAACA TGAAGTCGTT GTGAGGGTTA AAGGCAGTAA CAGGTATAAA GTACTTAGAA AAGCAAAGGG TGCTACGTAC ATGTGAGGCA TCATTACGCA GACGTAACTG GGATATGTTT ACTATAAGGA AAAGACACTG AGGTCTAGAA ATAGCTCCGT GGAGCAGAAT CAGTATTGGG AGCCGGTGGC GGTGTGAAGC ACCAGTGTCT GGCACACAGT 30 AGGTGCTCAT TGGCTCCCTT CCACCTGTCA TTCCCACCAC CCTGAGGCCC CAACCGCCAC ACACACAGGA GCATTTGGAG AGAAGGCCAT GTCTTCAAAG TCTGATTGT GATGAGGCAG AGGAAGATAT TTCTAATCGG TCTTGCCCAG AGGATCACAG TGCTGAGACC CCCCACCACC AGCCGGTACC TGGGAAGGGG GAGAGTGCAG GCCTGCTCAG GGACTGTTICC TGTCTCAGCA ACCAAGGGAT TGTTCCTGTC AATCAATGGT TTATTGGAAG GTGGCCCAGT ATGAGCCCTA GAAGAGTGTG AAAAGGAATG GCAATGGTGT TCACCATCGG CAGTGCCAGG 35 GCAGCACTCA TTCACTTGAT AAATGAATAT TTATTAGCTG GTTGGAGAGC TAGAACCTGG AGAGCTAGAA CCTGGAGAAC TAGAACCTGG AGGGCTAGAA CCTGGAGAGG CTAGAACCAA GAAGGGCTAG AACCTGGAGG GGCTAGAACC TAGAGAAGCT AAAACCTGAG CTAGAAGCTG GAGGACTAGA ACCTGGAGGG CTGGAATCTG AAGGGCTAGA ACCTGGAGGG CTGGAATCTG GAGAGCTAGA ACCTGGAGGG CTAGAACCTG GAGGGCTAGA ACCTAGAAGG GCTAGAACCT GGAGGGCTGG AATCTGGAGA GCTAGAACCT GGAGGGCTAG AACCTGGAGG 40 GCTAGAACCT AGAAGGGCTA GAACCTGGAG GGCTAGAACC TGGCAGGTTA GAACCTAGAA GGGCTAGAAC CTGGAGAGCC AGAACCTGGA GGGCTAGAAC CTGGAAGGGC TAGAACCTGT AGAGCTAGAA CATGGAGAGC TAGAACCCGG CAGGCTAGAA CCTGGCAAGC TAGAACCTGG AGGGAATGAA CCTGGAGGGC TAGAACCTGG AGAATGAGAA AAATTTACAT GGCAAAGAGC CCATAAATCC TGACCAATCC AACTCTGAAT TTTAAAGCAA AAGCGTGAAA AAAAAGATTC CCTCCTTACC CCCAACCCAC TCTTTTTTCC CACCACCCAC TCTCCTCTGC 45 CTCAGTAAGT ATCTGGAGGA AGAAAACAGG TGAAAGAAGA AGTAAAAACC ATTTAGTATr AGTATTAGAA TGAAGTCAAA CTGTGCCACA CATGGTGAAT GAAAAAAAAA AAAAAGAGGC TGTGTTTTGT CACACAGGGC AGTCATTCAG CACCAGAGCA CGTGATGGTC TGAGACTCTC TTAGGAGCAG AGCTCTGCCG CAATGGCCAT GTGGGGATCC ACACCTGGTC TGAGGGGCAA CTGAGTCTGC GGGAGAAGAG CGGCCCTATG CATGGTGTAG ATGCCCTGAT AAAGAACATC TGTCCTGTGA AAGACTCAAT GAGCTGTTAT GTTGTAAACA GGAAGCATTT 50 CACATCCAAA CGAGAAAATC ATGTAAACAT GTGTCTTTTC TGTAGAGCAT AATAAATGGA TGAGGTTT GCAAAAAAAA AAAAAAAAA AAATGATAGA CCGTCAATAA TTTGT[AAAT GCT=TTAAA ATGAATGCTT TAAGCCGGGT GCAGTGCCTC ACATCTGTAA TCCCAGCACT TTGGAGCCGA GCGGGTGGAT TGTGTGAGGT CAGGAGTTCG AGACCAACCT GGCCAACATG GCAAAACCTC ACTCTCTACC AAAAATACAA AAATTAGCCA GGCATGGTGG CAGGCACCTG TGATCCCAGC TACTCAGGAG GCTGAGACAG GAGAATCGCT TGAACCCGGG 55 AGGCAAGGTT GCAGTGAGCC AAGATTACGC CATTGTACTC CAGCCTGGGT GACAGAGAGA GACTCCGTCT CAAAAAAAAA AAAAAAAAAA AAAAAATFAC GCTTCAAACA CATGATCTCT CACCACTGTT GAATTTTCTT WO 00/62736 PCT/US00/08020 31 TCTATGAGCC CAGGAGGGCC TCTCAGAGAG GAAAGCTCCT AGGTCTTCCT TTCCCTCTGC AAACTCCCTG CCTTGAAGGT TCAGAAGGAC TGTGCGTGCT CGTTGCATCC TTTGCAAGTG TCCAAACCCT GATCCCAGCT GTGCTTAGGG GTTCCTGCAA ACCTITTCCA GGTGTTAATT ACCTCCCACT TCATTTCCTG TTTACCAACT CAGCTTTTTG TTTTAGTGTG TTTGAATTCC CTGAACTGAC CGTTGTCTGA TCTCCACCTC CCAACTGAAT 5 TAGGGGAGCT GGGCTTCTGG AAACCCAGGT GCCGGGTGTT GCAGAGTGGC TGAAAGCTGG GATGTGGCAG ATCCGTGGCT ACATTCATGC ACACACACAC ACCCACATAC CCACACATGC ACACACACAC ACACACCCGC ACTCACACAC TTGGACATGC ATAGACCACA GCTTTCCACA CCCTTCCTAG ACAGGGGTCA CTTGGTATCC TGGAGAGAGT GTGAAGTCCT GGAATGGAAA GAGGGGGGAT TAAGCCCCAC CTCTAGCCAT GGGACTGAGA CAAGTCACCA CCAACCCATC TGCGCCTTGT TTACCTCCTC TGTGAGGCAA GCACAGAGCC CATGCCTGCC 10 CCCCTGGATG GGAGTGATGT GAAACTTGAA GGGCGGTCAG AGCAAGGGTC GGGAATGGAA GGCCCTTGGG AAAAAAGGCC CTTTCAACTA GGGGCACAGA GGAGGCCCTG GGCTGAGAAC TTGACAGCAC CTTGTAATTG GTAAGCCAAG CCCGAAGGGA CTGGAAATAC TCAGATGTGT CTGTCTCCCT TATTAGGTTC AAAGTCCCTC AAGACCCTGT CTCCATCACA GTGCTCCAGT CCAGACCCCT CCTCTGAGCT CCAGACCCTG CTGGACCCAA CCAGCCCTAT GGGGTCGCAT CCCCACCTGC CTGGAATTCT CCAAAGAACC TCCCCTTTAA CAGTTCCAGC 15 CTTTAACAGT TCCAGTCTAA ACACATGACC TTTCTCCTCT AAATCAGCCC CCCATCTCTG CCTTTGCAGG AGATGGAAGC CATGACACCT GCCTCGCCCC TGTCCTCACC CCATCCATGT CCAATCAAGC ACTAGGCATG TCAGGTTTAC CCTCTAAACT CCTCTGGAAT CCAGTCTCTC AGTCTCCATC ATCCCAGGTC GAAGCTAATG GGCTAACTGG TCCTTGCTTC CACTCTACCC CCACTGCAGT CCTGACTTCC TGAGCAGCAG CCAGGGCCTA ATCGATATTC ACACCAAGCG CCAACCTGAC TGAGATATCC TCCTGCACCA TCATCCCTCC ACCCTGTTTA 20 GTTCTGCTCA CCCTCAGTGT TCTCATCAAT AATCCACTCC CCTCACAGGC GCGTTGGGA CCCCATGTTC TATGCTCTCA CAGGACCTT TGCTTGATTT TTCACTGTAC TTAGGTCAGT TTGCAGTTAT TAAGTGACTG AGCAATGTCT GGCTTCTCCA GTAGACTGTC AGCTCCTAGC CATTGTATAC CTAGCACCGC TGTGTGGGAG CACGTGACAA ACGTCCAGTG AGTCAGGGAC TCAGCAGTCT CCATTCTCC GCCCTGCTGG AGAATGCGTG TATTTGGCAA TCCCCAGCCC CTGTGCCATC TAACCATCTT TTCTTCTCTG TTCAGCCCAG GTGTGGCCTC 25 ACTCACATCC CACTCTGAGT CCAAATGTTC TCTCCCTGGA AGATATCAAT GTfTCTGTCT GTrCGTGAGG ACTCCGTGCC CACCACGGCC TCTTTCAGGT GAGTCAAAGG GATTCCTCAG TTCACTAGTT AGGGGAGGTG GGCAGACACC CTGGAGAACT CCCTGGAAAG CTCAACTCTC ATGCCCCGGA CAACAGTTGA AGGAACCATG GTGATGTTAA GCCCAAAGAC AAAACCTCTC AGGTGTCCAA GTCCCTGTTG GAATCTTGGG AGCAGAGGGA ATGTTCTGTG GTCTAGAGGA AGAGGGGCTC AGGGAGGAGA AGGGCACATT CCTGGTTGTT ATATGTTTCT 30 ATCTATCCCA GATGAACTTG GAAGTGAAGG GAAGAGAGTT AAACATTAAA GTAAATACCC AGTGGATCAG ACAGCAATGT GCCAGATTGC CTTGGAAACA AAATATCTCC AACACATGGC TGACATTTGG TGGGAGATCA GAACACCCTA AAGAGAGAAT TTAAGGGGAG GGGGAGGAGG ACCTGAGCCA GAGTAGAAGC AGAGGATAGG GAGATCTGTT CTTGGGGACA GCATTTGCAA GAAACAAGGC TGAGGGGTCC ACTCCAACCT CTCCACCCTG CTGCAGGTGC TGCCTATGAT GAAGATGAGC AGATGGCCAT CTCAGCTGGG GCCACAGTGC ACTGGACCTA 35 TAGTTTCCAA TTCCGCACTC AGCAGGCATC TTTCTGATGA TCCGATGGCT TCTCAGAGCC AGGGATGGGC CAGGATCCAT CCCCTTGGCT ACTGTCTTGC TGAGAAATTT ATAAGCAGCA TCTGGTGCTA TACTTTGGTC TCTAGTGAGT TAGCTCATGA AAGATGATAG ACTCTCCAAG CCAGGGGTAT GCAGGAAATG GGTTCTGT AGCTACAGAA ATGGGGTTGA GGGTTGGACC AAGGGACTAC CCAGGGGAAG TCTTACCTTC AGAGGACTCT GGAAAGGAGG CTGCAAGTTT TCATGGGTCA AGAATTCAGA GCCCAGTAGA GACAGCTTAT CTCTGTTCCA 40 AGATGTCTGG GGCCTTGGTT GGAAGATTCA AAGGCTAGGA AACCAGGAGC CACCAAAAGC GTAACTGGGG CCAGAGGATC CACTTTCAAG GTGGCAAGTT GGTTCCCCCC ATGTGGCTGC TTGAGTATCC TCACATGGCG GCTCACATCC TTCCAAGTAA GCAATGCAAA AGGCCAAGAA AGATGCTGCA AAGATGTTAT GACCTAGCCT CAGAAATCAC ACACCATCCC TGCCACCATT AGTAAGAAGT CCAGCCCACG TCCAGGAGAA GAGGAAGCAG ATTCCTCCTT TTGAAATGAA GAATATCAAG TAATTCGGGG GGCATATGAA AGCCACCACA CACCACAGGG 45 ATCTTAG AGCATACTTC TTATACCATC ACTGTAGTTC CTTAAGACTC AGGGGCAAAG CCTCACTTCC TTAGCACCCA GTGAAGACCA CGCTTACTCC CTCACTCAAC CTCTTGCTAC TTCCCACCTC TCCTGTCCAA CATCTAGTGT CACTTTCCAG AACATACCAA CAGCTTCCCC AGTTCTGTGC CTCTGCTCAG GCTGTTCCCC CTGCCTGGTC CACTTGTCCT CCTTCTTGTC CGGTCAAAAT GCTTCTTATC CTTCAAGACC CAGCTCTAGA GTCACCTCCA ACCCCTTACC CACCAGCCCC CTCTCCAAGT CTGTGTCCCA CAACCCCCCT GCTCCCTCCA 50 GGGCACCCTC CACCCTCTGG GCCACAGTTG TCAGGAGTCA GGCAGGGCAG GGGCCGGGTG GTGTCTTCTT TGTGTTCTTG CACTCAGGGC AGAGCTCAGC ACAGAGCAGA CGCTCAAAAA ACATTTAAAG GATAGAAGCA TTGATTTGTG GGTCCCCCAG TCTGGCTCCA GGATGCCAGC CAGCTGCTCC TAGAAGCAAA CGGACTTTTC CTGGGAAATC CCAGAGGTGA TGATCAGTAA TCTCTCCCGT GACTCGTAGT TCAGCTCTTC CTCCATGAGC CTGACTATCA GTGGACCTTC CAGAAAGAGC CCCTTTTCCT TCTCTCACCC ACAGCACAGG GCACTGGGAA 55 AATGCCCAAT GAGTCCTGCC TCTGGGTTGT GCTGGACT TTTCAGTGTG TCTCGCATCC ACTCTTCAAC TTGAATGTTG CAACAGCCAT GAAAAAAGAA ATGCAAAGCG ATTCAGGATG AGAGCAATAC CCTACTCCAA WO 00/62736 PCT/USOO/08020 32 AGAAGGCAAC ATAGAAGCTC AGAGAGATCA AGCAATTTGC CCAAGACCAC ACAGCTAGGA GTGGAACTCA TGGCTGTCCA AGCCCCATGC CTCTGCTGAA GGTAGAGATG AATTACAGCA ACAAGTCTAG AAAGGTGCCT GCCCTATGGT CTGTGAGTCT TGCCTAAGAA TGAAAGAGGA GCCAGTGGGT TAAAGATGAG GTCACCAACA ACGGTGGTGT TGGAGTTTAC CACTGATAAT AAGGGTGCAA AATGTAAATT ACTAATGTTT ATTGAGCCTA 5 GTGCAGTGCG TGGGGCATTT TGCACATTGT CTCTGATCCC TATGACAACC CTGAGAGGTA GTGGTTTTAA CTGCCATGTT ACAGGTGAGG TCATTGTGGT TCAAGGACGT TAAGTAACTT CCCCAGCGTG ACACGGCTITA TAAGTAAGGC AGCCAGGATG TGAACCCAGT AGGACTATCT GGCTGCAAAG TCCCCACCCC CCTCGCCATC TGTATCCTCC AATCACTTCA GTGCTTGCT GCATAGAAGG TAACGGAAAT CACGATGCCA CAGACTGTCC AGGAAGACAG AAACTAGGCA GATGGGCTGG CCATGGTCTC CAAGCCAGAC TGGAATCTCC AGGTCTGGAA 10 TGATATCATT TTTCTCTTTT AATAAATTAA CTCACCCACC ACACGGCT GAGAGGCTCA AAGTTGACCA ACTCCCTTGG GAGGGCCCCG GTTGATAAGG AAGGAACGTG AATCCTCCCA TCACGGAAGC TTCAAGGAGG TCAAGGGTCC AACACTTGAG ATTGTTAGTG CTGTTGGTGG ATACTGGCCA AGGAAATATC CCAGTGGAGC CTCGAGATGA AGAACATGAG GCCCCCGTTT AGAACCAAGG ATCAGAGGGG GCTCTGTAAG ACCCAGGGGA GTCAGGTGCA CTGGAGCGCG GGCATGCAGA AAACAGCCTG AGCTCCACCT CGGCTTCTCC TTGTCCTGGC 15 TGGTTGTCCT TAACCCCTGT CTCCTTCTGG ACCAGTTTTT GTCCTTCCCT TGTGACCGCT GAGGGGTAAC AGCCTCTTTC CACTTTCTTT CAGCGCCGAC ATGCTCAATG TCACCTTGCA AGGGCCCACT CTTAACGGGA CCTTTGCCCA GAGCAAATGC CCCCAAGTGG AGTGGCTGGG CTGGCTCAAC ACCATCCAGC CCCCCTTCCT CTGGGTGCTG TTCGTGCTGG CCACCCTAGA GAACATCTTT GTCCTCAGCG TCTTCTGCCT GCACAAGAGC AGCTGCACGG TGGCAGAGAT CTACCTGGGG AACCTGGCCG CAGCAGACCT GATCCTGGCC TGCGGGCTGC 20 CCTTCTGGGC CATCACCATC TCCAACAACT TCGACTGGCT C'TTTGGGGAG ACGCTCTGCC GCGTGGTGAA TGCCATTATC TCCATGAACC TGTACAGCAG CATCTGTTTC CTGATGCTGG TGAGCATCGA CCGCTACCTG GCCCTGGTGA AAACCATGTC CATGGGCCGG ATGCGCGGCG TGCGCTGGGC CAAGCTCTAC AGCTTGGTGA TCTGGGGGTG TACGCTGCTC CTGAGCTCAC CCATGCTGGT GTTCCGGACC ATGAAGGAGT ACAGCGATGA GGGCCACAAC GTCACCGCTT GTGTCATCAG CTACCCATCC CTCATCTGGG AAGTGTTCAC CAACATGCTC 25 CTGAATGTCG TGGGCTTCCT GCTGCCCCTG AGTGTCATCA CCT7CTGCAC GATGCAGATC ATGCAGGTGC TGCGGAACAA CGAGATGCAG AAGTTCAAGG AGATCCAGAC GGAGAGGAGG GCCACGGTGC TAGTCCTGGT TGTGCTGCTG CTATTCATCA TCTGCTGGCT GCCCTTCCAG ATCAGCACCT TCCTGGATAC GCTGCATCGC CTCGGCATCC TCTCCAGCTG CCAGGACGAG CGCATCATCG ATGTAATCAC ACAGATCGCC TCCTTCATGG CCTACAGCAA CAGCTGCCTC AACCCACTGG TGTACGTGAT CGTGGGCAAG CGCTTCCGAA AGAAGTCTTG 30 GGAGGTGTAC CAGGGAGTGT GCCAGAAAGG GGGCTGCAGG TCAGAACCCA TTCAGATGGA GAACTCCATG GGCACACTGC GGACCTCCAT CTCCGTGGAA CGCCAGATTC ACAAACTGCA GGACTGGGCA GGGAGCAGAC AGTGAGCAAA CGCCAGCAGG GCTGCTGTGA ATTTGTGTAA GGATTGAGGG ACAGTTGCTT TTCAGCATGG GCCCAGGAAT GCCAAGGAGA CATCTATGCA CGACCTTGGG AAATGAGTTG ATGTCTCCGG TAAAACACCG GAGACTAATT CCTGCCCTGC CCAATTGC AGGGAGCATG GCTGTGAGGA TGGGGTGAAC TCACGCACAG 35 CCAAGGACTC CAAAATCACA ACAGCATTAC TGTTCTTATT TGCTGCCACA CCTGAGCCAG CCTGCTCCTT CCCAGGAGTG GAGGAGGCCT GGGGGCAGGG AGAGGAGTGA CTGAGCTTCC CTCCCGTGTG TTCTCCGTCC CTGCCCCAGC AAGACAACTT AGATCTCCAG GAGAACTGCC ATCCAGCTTT GGTGCAATGG CTGAGTGCAC AAGTGAGTTG TTGCCCTGGG TTTCTTTAAT CTATTCAGCT AGAACTTTGA AGGACAATTT CTTGCATTAA TAAAGGTTAA GCCCTGAGGG GTCCCTGATA ACAACCTGGA GACCAGGATT TTATGGCTCC CCTCACTGAT 40 GGACAAGGAG GTCTGTGCCA AAGAAGAATC CAATAAGCAC ATATTGAGCA CTTGCTGTAT ATGCAGTATT GAGCACTGTA GGCAAGAGGG AAGAAAGAGA AGGAGCCATC TCCATCTTGA AGGAACTCAA AGACTCAAGT GGGAACGACT GGGCACTGCC ACCACCAGAA AGCTGTTCGA TGAGACGGTC GAGCAGGGTG CTGTGGGTGA TATGGACAGC AGAAGGGGGA GCCAGGTTCC AGCTCACCAA TACTATTGCA CACCACCTGT CCTGCCTC CTGCAGAAAA CAGCCTGAGC TCCACCTCGG CTTCTCCTTG CCCTGGCTGG TTGTCCTTAA CCCCTGTCTC 45 CTTCTGGACC AGTTTTTGTC CTTCCCTTGT GACCCTGAGG GGTAACAGCC TCTTTCCAC TTTCTTTCAG CGCCGACATG CTCAATGTCA CCTTGCAAGG GCCCACTCTr AACGGGACCT TTGCCCAGAG CAAATGCCCC CAAGTGGAGT GGCTGGGCTG GCTCAACACC ATCCAGCCCC CCTTCCTCTG GGTGCTGTTC GTGCTGGCCA CCCTAGAGAA CATCTTTGTC CTCAGCGTCT TCTGCCTGCA CAAGAGCAGC TGCACGGTGG CAGAGATCTA CCTGGGGAAC CTGGCCGCAG CAGACCTGAT CCTGGCCTGC GGGCTGCCCT TCTGGGCCAT CACCATCTCC 50 AACAACTTCG ACTGGCTCTT TGGGGAGACG CTCTGCCGCG TGGTGAATGC CATTATCTCC ATGAACCTGT ACAGCAGCAT CTGTTTCCTG ATGCTGGTGA GCATCGACCG CTACCTGGCC CTGGTGAAAA CCATGTCCAT GGGCCGGATG CGCGGCGTGC GCTGGGCCAA GCTCTACAGC TTGGTGATCT GGGGGTGTAC GCTGCTCCTG AGCTCACCCA TGCTGGTGTT CCGGACCATG AAGGAGTACA GCGATGAGGG CCACAACGTC ACCGCTrGTG TCATCAGCTA CCCATCCCTC ATCTGGGAAG TGTTCACCAA CATGCTCCTG AATGTCGTGG GCTTCCTGCT 55 GCCCCTGAGT GTCATCACCT TCTGCACGAT GCAGATCATG CAGGTGCTGC GGAACAACGA GATGCAGAAG TTCAAGGAGA TCCAGACGGA GAGGAGGGCC ACGGTGCTAG TCCTGGTTGT GCTGCTGCTA TTCATCATCT WO 00/62736 PCT/USOO/08020 33 GCTGGCTGCC CTTCCAGATC AGCACCTTCC TGGATACGCT GCATCGCCTC GGCATCCTCT CCAGCTGCCA GGACGAGCGC ATCATCGATG TAATCACACA GATCGCCTCC TTCATGGCCT ACAGCAACAG CTGCCTCAAC CCACTGGTGT ACGTGATCGT GGGCAAGCGC TTCCGAAAGA AGTCTTGGGA GGTGTACCAG GGAGTGTGCC AGAAAGGGGG CTGCAGGTCA GAACCCATTC AGATGGAGAA CTCCATGGGC ACACTGCGGA CCTCCATCTC 5 CGTGGAACGC CAGATTCACA AACTGCAGGA CTGGGCAGGG AGCAGACAGT GAGCAAACGC CAGCAGGGCT GCTGTGAATT TGTGTAAGGA TTGAGGGACA GTTGCTTC AGCATGGGCC CAGGAATGCC AAGGAGACAT CTATGCACGA CCTTGGGAAA TGAGTTGATG TCTCCGGTAA AACACCGGAG ACTAATTCCT GNCCTGCCCA ATTTTGCAGG GAGCATGGCT GTGAGGATGG GGTGAACTCA CGCACAGCCA AGGACTCCAA AATCACAACA GCATTACTGT TCTTATTTGC TGCCACACCT GAGCCAGCCT GCTCCTTCCC AGGAGTGGAG GAGGCCTGGG 10 GGCAGGGAGA GGAGTGACTG AGCTTCCCTC CCGTGTGTTC TCCGTCCCTG CCCCAGCAAG ACAACTTAGA TCTCCAGGAG AACTGCCATC CAGCTGGT GCAATGGCTG AGTGCACAAG TGAGTTGTTG CCCTGGGTTT CTTTAATCTA TTCAGCTAGA ACTTTGAAGG ACAATTCTT GCATTAATAA AGGTTAAGCC CTGAGGGGTC CCTGATAACA ACCTGGAGAC CAGGATTTTA TGGCTCCCCT CACTGATGGA CAAGGGAGGT CTGTGCCAAA GAAGAATCCA ATAAGCACAT ATTGAGCACT TGCTGTATAT GCAGTATTGA GCACTGTAGG CAAGAGGGAA 15 GAAAGAGAAG GAGCCATCTC CATCTTGAAG GAACTCAAAG ACTCAAGTGG GAACGACTGG CACTGCCACC ACCAGAAAGC TGTTCGACGA GACGGTCGAG CAGGGTGCTG TGGGTGATAT GGACAGCAGA AGGGGGAGAC CAAGGTTCCA GCTCAACCAA TAACTATTGC ACAACCACCT GTCCCTGCCT CAGTTCCCTC TTCTGTAACA TGAAGTCGTT GTGAGGGTTA AAGGCAGTAA CAGGTATAAA GTACTTAGAA AAGCAAAGGG TGCTACGTAC ATGTGAGGCA TCATTACGCA GACGTAACTG GGATATGTTT ACTATAAGGA AAAGACACTG AGGTCTAGA 20 TGATCCTATC ACAACCTGAG AGTAGTT ACTCCATTTA CAGGTGAGGT CATTGTGGTT CAAGGACGTT AAGTAACTTC CCCAGCTCAC ACGGCTTATA AGTAAGGCAG CCAGGATGTG AACCCAGTAG GACTATCTGG CTGCAAAGTC CCCACCCTCC CTCGCCATCT GTATCCTCCA ATCATCTTCA GTGCTTTGCT GATAGAAGGT ACGGAAATAC GATGCCACAG ACTGTCCAGG AAGACAGAAA CTAGGCAGAT GGGCTGGCCA TGGTCTCCAA GCCAGACTGG AATCTCCAGG TCTGGAATGA TATCATTTTT CTCTTTTAAT AAATTAACTC ACCCACCACA 25 CGGCTTTGAG AGGCTCAAAG GTGACCAACT CCCTTGGGAG GGCCCCGGTT GATAAGGAAG GAATGTGAAT CCTCCCATCA CGGAAGCTTC AAGGAGGTCA AGGGTCCAAC ACTTGAGATT GTTAGTGCTG TTGGTGGATA CTGCAGAATA TCCAGTGGAG CCTCAGATGA AGAACATGAG GCCCCGTTTA GATCCAAGGA TCAGAGGGGG CTCTGTAAGA CCCAGGGGAG TCAGGTGCAC TGGAGCGCGG GCTGCAGAAA ACAGCCTGAG CTCCACCTCG GCTTCTCCTT GCCCTGGCTG GTTGTCCTTA ACCCCTGTCT CCTTCTGGAC CAGTTTTTGT CCTTCCCTTG 30 TGACCTGAGG GGTAACAGCC TCITTCCAC TTTCTTTCAG CGCCGACATG CTCAATGTCA CCTTGCAAGG GCCCACTCTT AACGGGACCT TTGCCCAGAG CAAATGCCCC CAAGTGGAGT GGCTGGGCTG GCTCAACACC ATCCAGCCCC CCTTCCTCTG GGTGCTGTTC GTGCTGGCCA CCCTAGAGAA CATCTGTC CTCAGCGTCT TCTGCCTGCA CAAGAGCAGC TGCACGGTGG CAGAGATCTA CCTGGGGAAC CTGGCCGCAG CAGACCTGAT CCTGGCCTGC GGGCTGCCCT TCTGGGCCAT CACCATCTCC AACAACTTCG ACTGGCTCTT TGGGGAGACG 35 CTCTGCCGCG TGGTGAATGC CATTATCTCC ATGAACCTGT ACAGCAGCAT CTGTCCTG ATGCTGGTGA GCATCGACCG CTACCTGGCC CTGGTGAAAA CCATGTCCAT GGGCCGGATG CGCGGCGTGC GCTGGGCCAA GCTCTACAGC TTGGTGATCT GGGGGTGTAC GCTGCTCCTG AGCTCACCCA TGCTGGTGTT CCGGACCATG AAGGAGTACA GCGATGAGGG CCACAACGTC ACCGCTTGTG TCATCAGCTA CCCATCCCTC ATCTGGGAAG TGTTCACCAA CATGCTCCTG AATGTCGTGG GCTTCCTGCT GCCCCTGAGT GTCATCACCT TCTGCACGAT 40 GCAGATCATG CAGGTGCTGC GGAACAACGA GATGCAGAAG TTCAAGGAGA TCCAGACGGA GAGGAGGGCC ACGGTGCTAG TCCTGGTTGT GCTGCTGCTA TTCATCATCT GCTGGCTGCC CTTCCAGATC AGCACCTTCC TGGATACGCT GCATCGCCTC GGCATCCTCT CCAGCTGCCA GGACGAGCGC ATCATCGATG TAATCACACA GATCGCCTCC TTCATGGCCT ACAGCAACAG CTGCCTCAAC CCACTGGTGT ACGTGATCGT GGGCAAGCGC TTCCGAAAGA AGTCTTGGGA GGTGTACCAG GGAGTGTGCC AGAAAGGGGG CTGCAGGTCA GAACCCATTC 45 AGATGGAGAA CTCCATGGGC ACACTGCGGA CCTCCATCTC CGTGGAACGC CAGATTCACA AACTGCAGGA CTGGGCAGGG AGCAGACAGT GAGCAAACGC CAGCAGGGCT GCTGTGAATT TGTGTAAGGA TTGAGGGACA GTTGCTTTC AGCATGGGCC CAGGAATGCC AAGGAGACAT CTATGCACGA CCTTGGGAAA TGAGTGTTGA TGTCTCCGGT AAAACACCGG AGACTAATTC CTGCCCTGCC CAATTTTCGA GGGAGCATGG CTGTGAGGAT GGGGTGAACT CACGCACAGC CAAGGACTCC AAAATCACAA CAGCATTACT GTTCTTATTT GCTGCCACAC 50 CTGAGCCAGC CTGCTCCTTC CCAGGAGTGG AGGAGGCCTG GGGGAGGGAG AGGAGTGACT GAGCTTCCCT CCCGTGTGTT CTCCGTCCCT GCCCCAGCAA GACAACTTAG ATCTCCAGGA GAACTGCCAT CCACGTTTGG TGCAATGGCT GAGTGCACAA GTGAGTTGTF GCCCTGGGTT TCTTTAATCT ATCAGCTAGA ACTTTGAAGG ACAATTTCTT GCATTAATAA AGGTTAAGCC CTGAGGGGTC CCTTGATAAC AACCTGGAGA CCAGGATTTT ATGGCTCCCC TCACTGATGG ACAAGGAGGT CTGTGCCAAA GAAGAATCAA TAAGCACATA TGAGCACTTC 55 TGTATATCAG TATTGAGCAC TGTAGGCA ATGTTCTCTC CCTGGAAGAT ATCAATGT CTGTCTGT GTGAGGACTC CGTGCCCACC ACGGCCTCTT TCAGCGCCGA CATGCTCAAT GTCACCTTGC AAGGGCCCAC WO 00/62736 PCT/USOO/08020 34 TCTTAACGGG ACCTTGCCC AGAGCAAATG CCCCCAAGTG GAGTGGCTGG GCTGGCTCAA CACCATCCAG CCCCCCTTCC TCTGGGTGCT GTTCGTGCTG GCCACCCTAG AGAACATCTT TGTCCTCAGC GTCTTCTGCC TGCACAAGAG CAGCTGCACG GTGGCAGAGA TCTACCTGGG GAACCTGGCC GCAGCAGACC TGATCCTGGC CTGCGGGCTG CCCTTCTGGG CCATCACCAT CTCCAACAAC TTCGACTGGC TC'TTGGGGA GACGCTCTGC 5 CGCGTGGTGA ATGCCATTAT CTCCATGAAC CTGTACAGCA GCATCTGTTT CCTGATGCTG GTGAGCATCG ACCGCTACCT GGCCCTGGTG AAAACCATGT CCATGGGCCG GATGCGCGGC GTGCGCTGGG CCAAGCTCTA CAGCTTGGTG ATCTGGGGGT GTACGCTGCT CCTGAGCTCA CCCATGCTGG TGTTCCGGAC CATGAAGGAG TACAGCGATG AGGGCCACAA CGTCACCGCT TGTGTCATCA GCTACCCATC CCTCATCTGG GAAGTGTfCA CCAACATGCT CCTGAATGTC GTGGGCTTCC TGCTGCCCCT GAGTGTCATC ACCTTCTGCA CGATGCAGAT 10 CATGCAGGTG CTGCGGAACA ACGAGATGCA GAAGTTCAAG GAGATCCAGA CGGAGAGGAG GGCCACGGTG CTAGTCCTGG TTGTGCTGCT GCTATTCATC ATCTGCTGGC TGCCCTTCCA GATCAGCACC TTCCTGGATA CGCTGCATCG CCTCGGCATC CTCTCCAGCT GCCAGGACGA GCGCATCATC GATGTAATCA CACAGATCGC CTCCTTCATG GCCTACAGCA ACAGCTGCCT CAACCCACTG GTGTACGTGA TCGTGGGCAA GCGCTTCCGA AAGAAGTCTT GGGAGGTGTA CCAGGGAGTG TGCCAGAAAG GGGGCTGCAG GTCAGAACCC ATTCAGATGG 15 AGAACTCCAT GGGCACACTG CGGACCTCCA TCTCCGTGGA ACGCCAGATT CACAAACTGC AGGACTGGGC AGGGAGCAGA CAGTGAGCAA ACGCCAGCAG GGCTGCTGTG AATTTGTGTA AGGATTGAGG GACAGTTGCT T ATGTTCTCTC CCTGGAAGAT ATCAATGT CTGTCTGTTC GTGAGGACTC CGTGCCCACC ACGGCCTCTT TCAGCGCCGA CATGCTCAAT GTCACCTTGC AAGGGCCCAC TCTTAACGGG ACCTTTGCCC AGAGCAAATG CCCCCAAGTG GAGTGGCTGG GCTGGCTCAA CACCATCCAG CCCCCCTTCC TCTGGGTGCT GTTCGTGCTG 20 GCCACCCTAG AGAACATCTT TGTCCTCAGC GTCTTCTGCC TGCACAAGAG CAGCTGCACG GTGGCAGAGA TCTACCTGGG GAACCTGGCC GCAGCAGACC TGATCCTGGC CTGCGGGCTG CCCTTCTGGG CCATCACCAT CTCCAACAAC TTCGACTGGC TCTTTGGGGA GACGCTCTGC CGCGTGGTGA ATGCCATTAT CTCCATGAAC CTGTACAGCA GCATCTGTTT CCTGATGCTG GTGAGCATCG ACCGCTACCT GGCCCTGGTG AAAACCATGT CCATGGGCCG GATGCGCGGC GTGCGCTGGG CCAAGCTCTA CAGCTTGGTG ATCTGGGGGT GTACGCTGCT 25 CCTGAGCTCA CCCATGCTGG TGTTCCGGAC CATGAAGGAG TACAGCGATG AGGGCCACAA CGTCACCGCT TGTGTCATCA GCTACCCATC CCTCATCTGG GAAGTGTTCA CCAACATGCT CCTGAATGTC GTGGGCTTCC TGCTGCCCCT GAGTGTCATC ACCTTCTGCA CGATGCAGAT CATGCAGGTG CTGCGGAACA ACGAGATGCA GAAGTTCAAG GAGATCCAGA CGGAGAGGAG GGCCACGGTG CTAGTCCTGG TTGTGCTGCT GCTATTCATC ATCTGCTGGC TGCCCTTCCA GATCAGCACC TTCCTGGATA CGCTGCATCG CCTCGGCATC CTCTCCAGCT 30 GCCAGGACGA GCGCATCATC GATGTAATCA CACAGATCGC CTCCTTCATG GCCTACAGCA ACAGCTGCCT CAACCCACTG GTGTACGTGA TCGTGGGCAA GCGCTTCCGA AAGAAGTCTT GGGAGGTGTA CCAGGGAGTG TGCCAGAAAG GGGGCTGCAG GTCAGAACCC ATTCAGATGG AGAACTCCAT GGGCACACTG CGGACCTCCA TCTCCGTGGA ACGCCAGATT CACAAACTGC AGGACTGGGC AGGGAGCAGA CAGTGAGCAA ACGCCAGCAG GGCTGCTGTG AATTTGTGTA AGGATTGAGG GACAGTTGCT T GCCCTTCAAA GATGAGCTGT TCCCGCCGCC 35 ACTCCAGCTC TGGCTTCTGG GCTCCGAGGA GGGGTGGGGA CGGTGGGGAC ATCAGGCTGC CCCGCAGTAC CAGGGAGCGA CTGAAGTGCC CATGCCGCTT GCTCCGGAGA AGGTGGGTGC CGGGCAGGGG CTGCTCCAGC CGCCTCACCT CTGCTGGGAG GACAAACTGT CCCAGCACAG AGGGAGGGAG GGAGGGCAGG CAGCGGGGAG AAGTTrCCCT GTGGTCGTGG GGAGTT GCCCTTCAAA GATGAGCTGT TCCCGCCGCC ACTCCAGCTC TGGCTTCTGG GCTCCGAGGA GGGGTGGGGA CGGTGGTGAC GGTGGGGACA TCAGGCTGCC CCGCAGTACC 40 AGGGAGCGAC TGAAGTGCCC ATGCCGCTTG CTCCGGAGAA GGTGGGTGCC GGGCAGGGGC TGCTCCAGCC GCCTCACCTC TGCTGGGAGG ACAAACTGTC CCAGCACAGA GGGAGGGAGG GAGGGCAGGC AGCGGGGAGA AGTTTCCCTG TGGTCGTGGG GAGTT GAGCTCTTCA ATATTTTAGT GAAAGCTATA GATGAGGCTC CATAGGGGAT AAAGCACAGA CACACCTT CAGAGGGCTT GTGGACTCTG GGCAGCCTGT CCATAGACCT CTGTCCCCAA CTGGCAAGTC AGGAAACTCC AGATTAAGGA GCCCCAATGT GGTTGAACAG CCAGGTGCAC 45 AGATGAGTCA ACCACACAGC CAGGCCAGGG AGGGCCTTCA CTCAAGAGCC TACAGCCAGT TCACAGCCAA GCCAGGGCTA GCGCCAGGCC ACCCATAAAC TGATCTGAGA CTCTGTTTCC CTGTCTCCAT GATGATGGGA TCAGGCTTGA TTGCTGGTTr GTAGGCTTGT TATGAATCAA GTCACAGGGA AGAGGAGCTG ATGGGCTGGG GGGACGTCCT CTGGCCCTCC TGTCTCTTCC CCAGATCCAC TGGGCCCACT CTTATCTGTT CTCTTCTGAA GGAAGGGTTT TAAGGCTTrCA AAAAAAAATG TTTGAAAGT CCCTGCCCTT TCCAGCTCCT ACCGTCTCAG 50 CCCTGGGAGT GTAAAGTGCT GCAGATAGTT AGTAAGTCTT TGAGCAAAAC TGAGAAAGCC AGCCTGAGCC TTGACATGGG AGAAACCTCC GCCATACATC TCCGAAGAAA CGGCCGCGTG TCTCAGGGGA GCGCAAACAC CCGTACCCAG GAAACAGGAC AGCTrCTGCC ACTGTCGCCC TTGGGAGCCG TACGTGGCAT GACAAAGAAA TCCCAGGACT CCGCCTGCCC ACCTGGCCAC CCTCTGTTTA CACCTTCCGC GTAAACGCCC ACTGTTTACA TCCAAAACTC AGACACAAAA TAACCACCTC AAGAAGATAA ATAATGATAA GAAATAAATG TrACGCGAGG 55 CAAATTTATT CACATGGGGC TTCCCAGGCC ACTGTGGT CAGCCGGGAG GGACGTTTTT GCCGTCCCAC GACTCCAACG GGCAGCCGGG CCTACGCAAA CATGGAAATC TTCCAAGAGC CTCCCTGGCC CCCAGGGCTC WO 00/62736 PCT/US00/08020 35 AGAGGGTGGC AGAGCGGAGA GCGAAGGTGG CCGCAGCCTI' CCCGGCCCCA CAGCCAGCCT GGCTCCAGCT GGGCAGGAGT GCAGAGCTCA GCTGGAGGCG AGGGGGAAGT GCCCAGGAGG CTGATGACAT CACTACCCAG CCCTTCAAAG ATGAGCTGTT CCCGCCGCCA CTCCAGCTCT GGCTrCTGGG CTCCGAGGAG GGGTGGGGAC GGTGGTGACG GTGGGGACAT CAGdCTGCCC CGCAGTACCA GGGAGCGACT GAAGTGCCCA TGCCGC'FrGC 5 TCCGGAGAAG GTGGGTGCCG GGCAGGGGCT GCTCCAGCCG CCTCACCTCT GCTGGGAGGA CAAACTGTCC CAGGACAGAG GGAGGGAGGG AGGGCAGGCA GCGGGGAGAA GTITCCCTGT GGTCGTGGGG AGTTGGGAAA AGTTCCCTTC CTCCGGAGG GAGG CAGA FTCACA AACTGCAGGA CTGGGCAGGG AGCAGACAGT GAGCAAACGC CAGCAGGGCT GCTGTGAATT TGTGTAAGGA TrGAGGGACA GTTGCTITC AGCATGGGCC CAGGAATGCC AAGGAGACAT CTATGCACGA CCTTGGGAAA TGAGTTGATG TCTCCGGTAA AACACCGGAG 10 ACTAATTCCT GCCCTGCCCA A1TIGCAGG GAGCATGGCT GTGAGGATGG GGTGAACTCA CGCACAGCCA AGGACTCCAA AATCACAACA GCA'ITACTGT TC11TNITTGC TGCCACACCT GAGCCAGCCT GCTCCTTCCC AGGAGTGGAG GAGGCCTGGG GGGAGG.GAGA GGAGTGACTG AGCTTCCCTC CCGTGTGTTC TCCGTCCCTG CCCCAGCAAG ACAACTT1AGA TCTCCAGGAG AACTGCCATC CAGCTTTGGT GCAATGGCTG AGTGCACAAG TGAGTI'GTTG CCCTGGGITT CTITAATCTA TTCAGCTAGA A=IIGAAGG ACAATThrCTT GCAT7AATAA 15 AGG TrAAGCC CTGAGGGGTC CCTGATAACA ACCTGGAGAC CAGGATITA TGGCTCCCCT CACTGATGGA CAAGGAGGTC TGTGCCAAAG AAGAATCCAA TAAGCACATA TTGAGCAC'rr GCTGTATATG CAGTATTGAG CACTGTAGGC AAGACCCAAG AAAGAGAAGG AGCCATCTCC ATCTTGAAGG AACTCAAAGA CTCAAGTGGG AACGACTGGG CACTGCCACC ACCAGAAAGC TGTTCGACGA GACGGTCGAG CAGGGTGCTG TGGGTGATAT GGACAGCAGA AGGGGGAGAC CAAGGTTCCA GCTCAACCAA TAACTATTGC ACAACCACCT GTCCCTGCCT 20 CAGTTCCC Fr TTATGTAACA TGAAGTCGTT1 GTGAGGGTTA AAGGCAGTAA CAGGTATAAA GTACTTAGAA AAGCAAAGGG TGCTACGTAC ATGTGAGGCA TCATTACGCA GACGTAACTG GGATATG=~ ACTATAAGGA AAAGACACTG AGGTCTAGAA ATAGCTCCGT GGAGCAGAAT CAGTATTGGG AGCCGGTGGC GGTGTGAAGC ACCAGTGTCT GGCACACAGT AGGTGCTCAT TGGCTCCC'IT CCACCTGTCA TT1CCCACCAC CCTGAGGCCC CAACCGCCAC ACACACAGGA GCATTTGGAG AGAAGGCCAT GTcYJ7CAAAG TCTGATTTGT GATGAGGCAG 25 AGGAAGATAT TTCTAATCGG TCTTGCCCAG AGGATCACAG TGCTGAGACC CCCCACCACC AGCCGGTACC TGGGAAGGGG GAGAGTGCAG GCCTGCTCAG GGACTGTTCC TGTCTCAGCA ACCAAGGGAT TGTTCCTGTC AATCAATGGT TTATTGGAAG GTGGCCCAGT ATGAGCCCTA GAAGAGTGTG AAAAGGAATG GCAATGGTGT TCACCATCGG CAGTGCCAGG GCAGCACTCA TTCACTTGAT AAATGAATAT TFATTAGCTG GTTGGAGAGC TAGAACCTGG AGAGCTAGAA CCTGGAGAAC TAGAACCTGG AGGGCTAGAA CCTGGAGAGG CTAGAACCAA 30 GAAGGGCTAG AACCTGGAGG GGCTAGAACC TAGAGAAGCT AAAACCTGAG CTAGAAGCTG GAGGACTAGA ACCTGGAGGG CTGGAATCTG AAGGGCTAGA ACGTGGAGGG CTGGAATCTG GAGAGCTAGA ACCTGGAGGG CTAGAACCTG GAGGGCTAGA ACCTAGAAGG GCTAGAACCT GGAGGGCTGG AATCTGGAGA GCTAGAACCT GGAGGGCTAG AACCTGGAGG GCTAGAACCT AGAAGGGCTA GAACCTGGAG GGCTAGAACC TGGCAGGTTA GAACCTAGAA GGGCTAGAAC CTGGAGAGCC AGAACCTGGA GGGCTAGAAC CTGGAAGGGC TAGAACCTGT 35 AGAGCTAGAA CATGGAGAGC TAGAACCCGG CAGGCTAGAA CCTGGCAAGC TAGAACCTGG AGGGAATGAA CCTGGAGGGC TAGAACCTGG AGAATGAGAA AAAT11ACAT GGCAAAGAGC CCATAAATCC TGACCAATCC AACTCTGAAT MTAAAGCAA AAGCGTGAAA AAAAAGA'ITC CCTCCTTACC CCCAACCCAC TCYTIT=CC CACCACCCAC TCTCCTCTGC CTCAGTAAGT ATCTGGAGGA AGAAAACAGG TGAAAGAAGA AGTAAAAACC ATrTAGTATT AGTA FTAGAA TGAAGTCAAA CTGTGCCACA CATGGTGAAT GAAAAAAAAA AAAAAGAGGC 40 TGTGTIMGT CACACAGGGC AGTCA LTCAG CACCAGAGCA CGTGATGGTC TGAGACTCTC YI7AGGAGCAG AGCTCTGCCG CAATGGCCAT GTGGGGATCC ACACCTGGTC TGAGGGGCAA CTGAGTCTGC GGGAGAAGAG CGGCCCTATG CATGGTGTAG ATGCCCTGAT AAAGAACATC TGTCCTGTGA AAGACTCAAT GAGCTGTrAT GTTGTAAACA GGAAGCAT'rr CACATCCAAA CGAGAAAATC ATGTAAACAT GTGTCTTC TGTAGAGCAT AATAAATGGA TGAGGT1TT GCAAAAAAAA AAAAAAAAA AAATGATAGA CCGTCAATAA TTrGTAAAT 45 GCTI=rAAA ATGAATGCTT TAAGCCGGGT GCAGTGCCTC ACATCTGTAA TCCCAGCACT 'FrGGAGCCGA GCGGGTGGAT TGTGTGAGGT CAGGAG PTCG AGACCAACCT GGCCAACATG GCAAAACCTC ACTCTCTACC AAAAATACAA AAATTAGCCA GGCATGGTGG CAGGCACCTG TGATCCCAGC TACTCAGGAG GCTGAGACAG GAGAATCGCT TGAACCCGGG AGGCAAGGTL1 GCAGTGAGCC AAGATTACGC CA117GTACTC CAGCCTGGGT GACAGAGAGA GACTCCGTCT CAAAAAAAAA AAAAAAAAAA AAAAAATTAC GCTI'CAAACA CATGATCTCT 50 CACCACTGTT GAATITT TCTATGAGCC CAGGAGGGCC TCTCAGAGAG GAAAGCTCCT AGGTCTTCCT TTCCCTCTGC AAACTCCCTG CCTrGAAGGT TCAGAAGGAC TGTGCGTGCT CGTTGCATCC TTTGCAAGTG TCCAAACCCT GATCCCAGCT GTGCTTAGGG GTTCCTGCAA ACCYITCCA GGTGTT1AATTr ACCTCCCACT TCATTTCCTG TFACCAACT CAGCTIT1G TTT7AGTGTG TTFGAATTCC CTGAACTGAC CGTTGTCTGA TCTCCACCTC CCAACTGAAT TAGGGGAGCT GGGCTTCTGG AAACCCAGGT GCCGGGTGTT GCAGAGTGGC 55 TGAAAGCTGG GATGTGGCAG ATCCGTGGCT ACAT7CATGC ACACACACAC ACCCACATAC CCACACATGC ACACACACAC ACACACCCGC ACTCACACAC TTGGACATGC ATAGACCACA GCTITCCACA CCCTTCCTAG WO 00/62736 PCT/USOO/08020 36 ACAGGGGTCA CTTGGTATCC TGGAGAGAGT GTGAAGTCCT GGAATGGAAA GAGGGGGGAT TAAGCCCCAC CTCTAGCCAT GGGACTGAGA CAAGTCACCA CCAACCCATC TGCGCCTTGT TTACCTCCTC TGTGAGGCAA GCACAGAGCC CATGCCTGCC CCCCTGGATG GGAGTGATGT GAAACTTGAA GGGCGGTCAG AGCAAGGGTC GGGAATGGAA GGCCCTTGGG AAAAAAGGCC CTTTCAACTA GGGGCACAGA GGAGGCCCTG GGCTGAGAAC 5 TTGACAGCAC CTTGTAATTG GTAAGCCAAG CCCGAAGGGA CTGGAAATAC TCAGATGTGT CTGTCTCCCT TATTAGGTTC AAAGTCCCTC AAGACCCTGT CTCCATCACA GTGCTCCAGT CCAGACCCCT CCTCTGAGCT CCAGACCCTG CTGGACCCAA CCAGCCCTAT GGGGTCGCAT CCCCACCTGC CTGGAATTCT CCAAAGAACC TCCCCTTTAA CAGTrCCAGC CTTTAACAGT TCCAGTCTAA ACACATGACC TTTCTCCTCT AAATCAGCCC CCCATCTCTG CCTTGCAGG AGATGGAAGC CATGACACCT GCCTCGCCCC TGTCCTCACC CCATCCATGT 10 CCAATCAAGC ACTAGGCATG TCAGGTTTAC CCTCTAAACT CCTCTGGAAT CCAGTCTCTC AGTCTCCATC ATCCCAGGTC GAAGCTAATG GGCTAACTGG TCCTTGCTTC CACTCTACCC CCACTGCAGT CCTGACTTCC TGAGCAGCAG CCAGGGCCTA ATCGATATTC ACACCAAGCG CCAACCTGAC TGAGATATCC TCCTGCACCA TCATCCCTCC ACCCTGTTTA GTTCTGCTCA CCCTCAGTGT TCTCATCAAT AATCCACTCC CCTCACAGGC GCGTTTGGGA CCCCATGTTC TATGCTCTCA CAGGACCTTT TGCTTGATTT TTCACTGTAC TTAGGTCAGT 15 TTGCAGTTAT TAAGTGACTG AGCAATGTCT GGCTTCTCCA GTAGACTGTC AGCTCCTAGC CATTGTATAC CTAGCACCGC TGTGTGGGAG CACGTGACAA ACGTCCAGTG AGTCAGGGAC TCAGCAGTCT CCATTTCTCC GCCCTGCTGG AGAATGCGTG TATTTGGCAA TCCCCAGCCC CTGTGCCATC TAACCATCTT TTCTTCTCTG TTCAGCCCAG GTGTGGCCTC ACTCACATCC CACTCTGAGT CCAAATGTTC TCTCCCTGGA AGATATCAAT GTTTCTGTCT GTTCGTGAGG ACTCCGTGCC CACCACGGCC TCTTrCAGGT GAGTCAAAGG GATTCCTCAG 20 TTCACTAGTT AGGGGAGGTG GGCAGACACC CTGGAGAACT CCCTGGAAAG CTCAACTCTC ATGCCCCGGA CAACAGTTGA AGGAACCATG GTGATGTTAA GCCCAAAGAC AAAACCTCTC AGGTGTCCAA GTCCCTGTTG GAATCTTGGG AGCAGAGGGA ATGTTCTGTG GTCTAGAGGA AGAGGGGCTC AGGGAGGAGA AGGGCACATT CCTGGTTGTT ATATGTTCT ATCTATCCCA GATGAACTTG GAAGTGAAGG GAAGAGAGTT AAACATTAAA GTAAATACCC AGTGGATCAG ACAGCAATGT GCCAGATTGC CTTGGAAACA AAATATCTCC AACACATGGC 25 TGACATTTGG TGGGAGATCA GAACACCCTA AAGAGAGAAT TTAAGGGGAG GGGGAGGAGG ACCTGAGCCA GAGTAGAAGC AGAGGATAGG GAGATCTGT7 CTTGGGGACA GCATTTGCAA GAAACAAGGC TGAGGGGTCC ACTCCAACCT CTCCACCCTG CTGCAGGTGC TGCCTATGAT GAAGATGAGC AGATGGCCAT CTCAGCTGGG GCCACAGTGC ACTGGACCTA TAGTTTCCAA TTCCGCACTC AGCAGGCATC YTCTGATGA TCCGATGGCT TCTCAGAGCC AGGGATGGGC CAGGATCCAT CCCCTTGGCT ACTGTCTTGC TGAGAAATTT ATAAGCAGCA 30 TCTGGTGCTA TACTTTrGGTC TCTAGTGAGT TAGCTCATGA AAGATGATAG ACTCTCCAAG CCAGGGGTAT GCAGGAAATG GGTTTTCTGT AGCTACAGAA ATGGGGTTGA GGGTTGGACC AAGGGACTAC CCAGGGGAAG TCTTACCTTC AGAGGACTCT GGAAAGGAGG CTGCAAGTTT TCATGGGTCA AGAATTCAGA GCCCAGTAGA GACAGCTTAT CTCTGTTCCA AGATGTCTGG GGCCTTGGTT GGAAGATTCA AAGGCTAGGA AACCAGGAGC CACCAAAAGC GTAACTGGGG CCAGAGGATC CACTTTCAAG GTGGCAAGTT GGTTCCCCCC ATGTGGCTGC 35 TTGAGTATCC TCACATGGCG GCTCACATCC TTCCAAGTAA GCAATGCAAA AGGCCAAGAA AGATGCTGCA AAGATGTTAT GACCTAGCCT CAGAAATCAC ACACCATCCC TGCCACCATT AGTAAGAAGT CCAGCCCACG TCCAGGAGAA GAGGAAGCAG ATTCCTCCTT TTGAAATGAA GAATATCAAG TAATTCGGGG GGCATATGAA AGCCACCACA CACCACAGGG ATCTTAG AGCATACTTC TTATACCATC ACTGTAGTTC CTTAAGACTC AGGGGCAAAG CCTCACTTCC TTAGCACCCA GTGAAGACCA CGCTTrACTCC CTCACTCAAC CTCTTGCTAC 40 TTCCCACCTC TCCTGTCCAA CATCTAGTGT CACTTTCCAG AACATACCAA CAGCTTCCCC AGTTCTGTGC CTCTGCTCAG GCTGTTCCCC CTGCCTGGTC CACTTGTCCT CCTTCTrGTC CGGTCAAAAT GCTTCTTATC CTTCAAGACC CAGCTCTAGA GTCACCTCCA ACCCCTTACC CACCAGCCCC CTCTCCAAGT CTGTGTCCCA CAACCCCCCT GCTCCCTCCA GGGCACCCTC CACCCTCTGG GCCACAGTTG TCAGGAGTCA GGCAGGGCAG GGGCCGGGTG GTGTCTTCTT TGTGTTCTTG CACTCAGGGC AGAGCTCAGC ACAGAGCAGA CGCTCAAAAA 45 ACATTTAAAG GATAGAAGCA TTGATTTGTG GGTCCCCCAG TCTGGCTCCA GGATGCCAGC CAGCTGCTCC TAGAAGCAAA CGGACTTC CTGGGAAATC CCAGAGGTGA TGATCAGTAA TCTCTCCCGT GACTCGTAGT TCAGCTCTTC CTCCATGAGC CTGACTATCA GTGGACCTTC CAGAAAGAGC CCCTTTTCCT TCTCTCACCC ACAGCACAGG GCACTGGGAA AATGCCCAAT GAGTCCTGCC TCTGGGT7GT GCTTTGGACT TTTCAGTGTG TCTCGCATCC ACTCTTCAAC TTGAATGTTG CAACAGCCAT GAAAAAAGAA ATGCAAAGCG ATTCAGGATG 50 AGAGCAATAC CCTACTCCAA AGAAGGCAAC ATAGAAGCTC AGAGAGATCA AGCAATTGC CCAAGACCAC ACAGCTAGGA GTGGAACTCA TGGCTGTCCA AGCCCCATGC CTCTGCTGAA GGTAGAGATG AATTACAGCA ACAAGTCTAG AAAGGTGCCT GCCCTATGGT CTGTGAGTCT TGCCTAAGAA TGAAAGAGGA GCCAGTGGGT TAAAGATGAG GTCACCAACA ACGGTGGTGT TGGAGTTTAC CACTGATAAT AAGGGTGCAA AATGTAAATT ACTAATGTTT ATTGAGCCTA GTGCAGTGCG TGGGGCAT TGCACATTGT CTCTGATCCC TATGACAACC 55 CTGAGAGGTA GTGGTTAA CTGCCATGTT ACAGGTGAGG TCATTGTGGT TCAAGGACGT TAAGTAACTT CCCCAGCGTG ACACGGCTTA TAAGTAAGGC AGCCAGGATG TGAACCCAGT AGGACTATCT GGCTGCAAAG WO 00/62736 PCT/USOO/08020 37 TCCCCACCCC CCTCGCCATC TGTATCCTCC AATCACTTCA GTGCTTGCT GCATAGAAGG TAACGGAAAT CACGATGCCA CAGACTGTCC AGGAAGACAG AAACTAGGCA GATGGGCTGG CCATGGTCTC CAAGCCAGAC TGGAATCTCC AGGTCTGGAA TGATATCATT TTTCTCTT AATAAATTAA CTCACCCACC ACACGGCTTT GAGAGGCTCA AAGTTGACCA ACTCCCTTGG GAGGGCCCCG GTTGATAAGG AAGGAACGTG AATCCTCCCA 5 TCACGGAAGC TTCAAGGAGG TCAAGGGTCC AACACTTGAG ATTGTTAGTG CTGTTGGTGG ATACTGGCCA AGGAAATATC CCAGTGGAGC CTCGAGATGA AGAACATGAG GCCCCCGTTT AGAACCAAGG ATCAGAGGGG GCTCTGTAAG ACCCAGGGGA GTCAGGTGCA CTGGAGCGCG GGCATGCAGA AAACAGCCTG AGCTCCACCT CGGCTTCTCC TTGTCCTGGC TGGTTGTCCT TAACCCCTGT CTCCTTCTGG ACCAGTT GTCCTTCCCT TGTGACCGCT GAGGGGTAAC AGCCTCTTTC CACTTTCTTT CAGCGCCGAC ATGCTCAATG TCACCTTGCA 10 AGGGCCCACT CTTAACGGGA CCTTTGCCCA GAGCAAATGC CCCCAAGTGG AGTGGCTGGG CTGGCTCAAC ACCATCCAGC CCCCCTTCCT CTGGGTGCTG TTCGTGCTGG CCACCCTAGA GAACATCTTT GTCCTCAGCG TCTTCTGCCT GCACAAGAGC AGCTGCACGG TGGCAGAGAT CTACCTGGGG AACCTGGCCG CAGCAGACCT GATCCTGGCC TGCGGGCTGC CCTTCTGGGC CATCACCATC TCCAACAACT TCGACTGGCT CTTTGGGGAG ACGCTCTGCC GCGTGGTGAA TGCCATTATC TCCATGAACC TGTACAGCAG CATCTGTTTC CTGATGCTGG 15 TGAGCATCGA CCGCTACCTG GCCCTGGTGA AAACCATGTC CATGGGCCGG ATGCGCGGCG TGCGCTGGGC CAAGCTCTAC AGCTTGGTGA TCTGGGGGTG TACGCTGCTC CTGAGCTCAC CCATGCTGGT GTTCCGGACC ATGAAGGAGT ACAGCGATGA GGGCCACAAC GTCACCGCTT GTGTCATCAG CTACCCATCC CTCATCTGGG AAGTGTTCAC CAACATGCTC CTGAATGTCG TGGGCTTCCT GCTGCCCCTG AGTGTCATCA CCTTCTGCAC GATGCAGATC ATGCAGGTGC TGCGGAACAA CGAGATGCAG AAGTTCAAGG AGATCCAGAC GGAGAGGAGG 20 GCCACGGTGC TAGTCCTGGT TGTGCTGCTG CTATTCATCA TCTGCTGGCT GCCCTrCCAG ATCAGCACCT TCCTGGATAC GCTGCATCGC CTCGGCATCC TCTCCAGCTG CCAGGACGAG CGCATCATCG ATGTAATCAC ACAGATCGCC TCCTTCATGG CCTACAGCAA CAGCTGCCTC AACCCACTGG TGTACGTGAT CGTGGGCAAG CGCTTCCGAA AGAAGTCTTG GGAGGTGTAC CAGGGAGTGT GCCAGAAAGG GGGCTGCAGG TCAGAACCCA TTCAGATGGA GAACTCCATG GGCACACTGC GGACCTCCAT CTCCGTGGAA CGCCAGATTC ACAAACTGCA 25 GGACTGGGCA GGGAGCAGAC AGTGAGCAAA CGCCAGCAGG GCTGCTGTGA ATTTGTGTAA GGATTGAGGG ACAGTTGCTT TTCAGCATGG GCCCAGGAAT GCCAAGGAGA CATCTATGCA CGACCTTGGG AAATGAGTTG ATGTCTCCGG TAAAACACCG GAGACTAATT CCTGCCCTGC CCAAYTTGC AGGGAGCATG GCTGTGAGGA TGGGGTGAAC TCACGCACAG CCAAGGACTC CAAAATCACA ACAGCATTAC TGTTCTTATT TGCTGCCACA CCTGAGCCAG CCTGCTCCTT CCCAGGAGTG GAGGAGGCCT GGGGGCAGGG AGAGGAGTGA CTGAGCTTCC 30 CTCCCGTGTG TTCTCCGTCC CTGCCCCAGC AAGACAACTT AGATCTCCAG GAGAACTGCC ATCCAGCTTT GGTGCAATGG CTGAGTGCAC AAGTGAGTTG TTGCCCTGGG TTTCTTTAAT CTATTCAGCT AGAACTTTGA AGGACAATTT CTTGCATTAA TAAAGGTrAA GCCCTGAGGG GTCCCTGATA ACAACCTGGA GACCAGGATT TTATGGCTCC CCTCACTGAT GGACAAGGAG GTCTGTGCCA AAGAAGAATC CAATAAGCAC ATATTGAGCA CT'TGCTGTAT ATGCAGTATT GAGCACTGTA GGCAAGAGGG AAGAAAGAGA AGGAGCCATC TCCATCTTGA 35 AGGAACTCAA AGACTCAAGT GGGAACGACT GGGCACTGCC ACCACCAGAA AGCTGTTCGA TGAGACGGTC GAGCAGGGTG CTGTGGGTGA TATGGACAGC AGAAGGGGGA GCCAGGTTCC AGCTCACCAA TACTATTGCA CACCACCTGT CCTGCCTC CTGCAGAAAA CAGCCTGAGC TCCACCTCGG CTTCTCCTTG CCCTGGCTGG TTGTCCTTAA CCCCTGTCTC CTTCTGGACC AGTTTGTC CTTCCCTTGT GACCCTGAGG GGTAACAGCC TCTTTTCCAC TTCTTTCAG CGCCGACATG CTCAATGTCA CCTTGCAAGG GCCCACTCTT AACGGGACCT 40 TTGCCCAGAG CAAATGCCCC CAAGTGGAGT GGCTGGGCTG GCTCAACACC ATCCAGCCCC CCTTCCTCTG GGTGCTGT7C GTGCTGGCCA CCCTAGAGAA CATCTTGTC CTCAGCGTCT TCTGCCTGCA CAAGAGCAGC TGCACGGTGG CAGAGATCTA CCTGGGGAAC CTGGCCGCAG CAGACCTGAT CCTGGCCTGC GGGCTGCCCT TCTGGGCCAT CACCATCTCC AACAACTTCG ACTGGCTCT TGGGGAGACG CTCTGCCGCG TGGTGAATGC CATTATCTCC ATGAACCTGT ACAGCAGCAT CTGTTTCCTG ATGCTGGTGA GCATCGACCG CTACCTGGCC 45 CTGGTGAAAA CCATGTCCAT GGGCCGGATG CGCGGCGTGC GCTGGGCCAA GCTCTACAGC TTGGTGATCT GGGGGTGTAC GCTGCTCCTG AGCTCACCCA TGCTGGTGTT CCGGACCATG AAGGAGTACA GCGATGAGGG CCACAACGTC ACCGCTTGTG TCATCAGCTA CCCATCCCTC ATCTGGGAAG TGTTCACCAA CATGCTCCTG AATGTCGTGG GCTTCCTGCT GCCCCTGAGT GTCATCACCT TCTGCACGAT GCAGATCATG CAGGTGCTGC GGAACAACGA GATGCAGAAG TTCAAGGAGA TCCAGACGGA GAGGAGGGCC ACGGTGCTAG TCCTGGTTGT 50 GCTGCTGCTA T7CATCATCT GCTGGCTGCC CTTCCAGATC AGCACCTTCC TGGATACGCT GCATCGCCTC GGCATCCTCT CCAGCTGCCA GGACGAGCGC ATCATCGATG TAATCACACA GATCGCCTCC TTCATGGCCT ACAGCAACAG CTGCCTCAAC CCACTGGTGT ACGTGATCGT GGGCAAGCGC TTCCGAAAGA AGTCTTGGGA GGTGTACCAG GGAGTGTGCC AGAAAGGGGG CTGCAGGTCA GAACCCATTC AGATGGAGAA CTCCATGGGC ACACTGCGGA CCTCCATCTC CGTGGAACGC CAGATTCACA AACTGCAGGA CTGGGCAGGG AGCAGACAGT 55 GAGCAAACGC CAGCAGGGCT GCTGTGAATT TGTGTAAGGA TTGAGGGACA GTTGCTC AGCATGGGCC CAGGAATGCC AAGGAGACAT CTATGCACGA CCTTGGGAAA TGAGTTGATG TCTCCGGTAA AACACCGGAG WO 00/62736 PCT/USOO/08020 38 ACTAATTCCT GNCCTGCCCA AT'TGCAGG GAGCATGGCT GTGAGGATGG GGTGAACTCA CGCACAGCCA AGGACTCCAA AATCACAACA GCATTACTGT TCTTATTTGC TGCCACACCT GAGCCAGCCT GCTCCTTCCC AGGAGTGGAG GAGGCCTGGG GGCAGGGAGA GGAGTGACTG AGCTTCCCTC CCGTGTGTrC TCCGTCCCTG CCCCAGCAAG ACAACTTAGA TCTCCAGGAG AACTGCCATC CAGCTTTGGT GCAATGGCTG AGTGCACAAG 5 TGAGTTGTTG CCCTGGGTTT CTTTAATCTA TTCAGCTAGA ACTTGAAGG ACAATTTCTT GCATTAATAA AGGTTAAGCC CTGAGGGGTC CCTGATAACA ACCTGGAGAC CAGGATTTTA TGGCTCCCCT CACTGATGGA CAAGGGAGGT CTGTGCCAAA GAAGAATCCA ATAAGCACAT ATTGAGCACT TGCTGTATAT GCAGTATTGA GCACTGTAGG CAAGAGGGAA GAAAGAGAAG GAGCCATCTC CATCTTGAAG GAACTCAAAG ACTCAAGTGG GAACGACTGG CACTGCCACC ACCAGAAAGC TGTTCGACGA GACGGTCGAG CAGGGTGCTG TGGGTGATAT 10 GGACAGCAGA AGGGGGAGAC CAAGGTTCCA GCTCAACCAA TAACTATTGC ACAACCACCT GTCCCTGCCT CAGTTCCCTC TTCTGTAACA TGAAGTCGTT GTGAGGGTrA AAGGCAGTAA CAGGTATAAA GTACTTAGAA AAGCAAAGGG TGCTACGTAC ATGTGAGGCA TCATTACGCA GACGTAACTG GGATATGTTT ACTATAAGGA AAAGACACTG AGGTCTAGA TGATCCTATC ACAACCTGAG AGTAGTTTTT ACTCCATTTA CAGGTGAGGT CATTGTGGTT CAAGGACGTT AAGTAACTTC CCCAGCTCAC ACGGCTTATA AGTAAGGCAG CCAGGATGTG 15 AACCCAGTAG GACTATCTGG CTGCAAAGTC CCCACCCTCC CTCGCCATCT GTATCCTCCA ATCATCTTCA GTGCTTTGCT GATAGAAGGT ACGGAAATAC GATGCCACAG ACTGTCCAGG AAGACAGAAA CTAGGCAGAT GGGCTGGCCA TGGTCTCCAA GCCAGACTGG AATCTCCAGG TCTGGAATGA TATCATTTTT CTCTTTTAAT AAATTAACTC ACCCACCACA CGGCTTTGAG AGGCTCAAAG GTGACCAACT CCCTTGGGAG GGCCCCGGTT GATAAGGAAG GAATGTGAAT CCTCCCATCA CGGAAGCTTC AAGGAGGTCA AGGGTCCAAC ACTTGAGATT 20 GTTAGTGCTG TTGGTGGATA CTGCAGAATA TCCAGTGGAG CCTCAGATGA AGAACATGAG GCCCCGTTTA GATCCAAGGA TCAGAGGGGG CTCTGTAAGA CCCAGGGGAG TCAGGTGCAC TGGAGCGCGG GCTGCAGAAA ACAGCCTGAG CTCCACCTCG GCTTCTCCTT GCCCTGGCTG GTTGTCCTTA ACCCCTGTCT CCTTCTGGAC CAGTTTTTGT CCTTCCCTTG TGACCTGAGG GGTAACAGCC TCTTTTCCAC TTTCTTTCAG CGCCGACATG CTCAATGTCA CCTFGCAAGG GCCCACTCTT AACGGGACCT TTGCCCAGAG CAAATGCCCC CAAGTGGAGT 25 GGCTGGGCTG GCTCAACACC ATCCAGCCCC CCTTCCTCTG GGTGCTGTTC GTGCTGGCCA CCCTAGAGAA CATCTTTGTC CTCAGCGTCT TCTGCCTGCA CAAGAGCAGC TGCACGGTGG CAGAGATCTA CCTGGGGAAC CTGGCCGCAG CAGACCTGAT CCTGGCCTGC GGGCTGCCCT TCTGGGCCAT CACCATCTCC AACAACTTCG ACTGGCTCTT TGGGGAGACG CTCTGCCGCG TGGTGAATGC CATTATCTCC ATGAACCTGT ACAGCAGCAT CTGTTTCCTG ATGCTGGTGA GCATCGACCG CTACCTGGCC CTGGTGAAAA CCATGTCCAT GGGCCGGATG 30 CGCGGCGTGC GCTGGGCCAA GCTCTACAGC TTGGTGATCT GGGGGTGTAC GCTGCTCCTG AGCTCACCCA TGCTGGTGTT CCGGACCATG AAGGAGTACA GCGATGAGGG CCACAACGTC ACCGCTTGTG TCATCAGCTA CCCATCCCTC ATCTGGGAAG TGTTCACCAA CATGCTCCTG AATGTCGTGG GCTTCCTGCT GCCCCTGAGT GTCATCACCT TCTGCACGAT GCAGATCATG CAGGTGCTGC GGAACAACGA GATGCAGAAG TTCAAGGAGA TCCAGACGGA GAGGAGGGCC ACGGTGCTAG TCCTGGTTGT GCTGCTGCTA TTCATCATCT GCTGGCTGCC 35 CTTCCAGATC AGCACCTTCC TGGATACGCT GCATCGCCTC GGCATCCTCT CCAGCTGCCA GGACGAGCGC ATCATCGATG TAATCACACA GATCGCCTCC TTCATGGCCT ACAGCAACAG CTGCCTCAAC CCACTGGTGT ACGTGATCGT GGGCAAGCGC TTCCGAAAGA AGTCTTGGGA GGTGTACCAG GGAGTGTGCC AGAAAGGGGG CTGCAGGTCA GAACCCATTC AGATGGAGAA CTCCATGGGC ACACTGCGGA CCTCCATCTC CGTGGAACGC CAGATTCACA AACTGCAGGA CTGGGCAGGG AGCAGACAGT GAGCAAACGC CAGCAGGGCT GCTGTGAATTI 40 TGTGTAAGGA TTGAGGGACA GTTGCTTTTC AGCATGGGCC CAGGAATGCC AAGGAGACAT CTATGCACGA CCTTGGGAAA TGAGTGTTGA TGTCTCCGGT AAAACACCGG AGACTAATTC CTGCCCTGCC CAATTTTCGA GGGAGCATGG CTGTGAGGAT GGGGTGAACT CACGCACAGC CAAGGACTCC AAAATCACAA CAGCATTACT GTTCTTATTT GCTGCCACAC CTGAGCCAGC CTGCTCCTTC CCAGGAGTGG AGGAGGCCTG GGGGAGGGAG AGGAGTGACT GAGCTTCCCT CCCGTGTGTT CTCCGTCCCT GCCCCAGCAA GACAACTTAG ATCTCCAGGA 45 GAACTGCCAT CCACGTTTGG TGCAATGGCT GAGTGCACAA GTGAGTTGTT GCCCTGGGTT TCTTTAATCT ATCAGCTAGA ACTTTGAAGG ACAATTTCTT GCATTAATAA AGGTTAAGCC CTGAGGGGTC CCTTGATAAC AACCTGGAGA CCAGGATTTT ATGGCTCCCC TCACTGATGG ACAAGGAGGT CTGTGCCAAA GAAGAATCAA TAAGCACATA TGAGCACTTC TGTATATCAG TATTGAGCAC TGTAGGCA ATGTTCTCTC CCTGGAAGAT ATCAATGTTT CTGTCTGTTT GTGAGGACTC CGTGCCCACC ACGGCCTCTT TCAGCGCCGA CATGCTCAAT 50 GTCACCTTGC AAGGGCCCAC TCTTAACGGG ACCTGCCC AGAGCAAATG CCCCCAAGTG GAGTGGCTGG GCTGGCTCAA CACCATCCAG CCCCCCTTCC TCTGGGTGCT GTTCGTGCTG GCCACCCTAG AGAACATCTT TGTCCTCAGC GTCTTCTGCC TGCACAAGAG CAGCTGCACG GTGGCAGAGA TCTACCTGGG GAACCTGGCC GCAGCAGACC TGATCCTGGC CTGCGGGCTG CCCTTCTGGG CCATCACCAT CTCCAACAAC TTCGACTGGC TCTTTGGGGA GACGCTCTGC CGCGTGGTGA ATGCCATTAT CTCCATGAAC CTGTACAGCA GCATCTGTTT 55 CCTGATGCTG GTGAGCATCG ACCGCTACCT GGCCCTGGTG AAAACCATGT CCATGGGCCG GATGCGCGGC GTGCGCTGGG CCAAGCTCTA CAGCTTGGTG ATCTGGGGGT GTACGCTGCT CCTGAGCTCA CCCATGCTGG WO 00/62736 PCT/USOO/08020 39 TGTTCCGGAC CATGAAGGAG TACAGCGATG AGGGCCACAA CGTCACCGCT TGTGTCATCA GCTACCCATC CCTCATCTGG GAAGTGTTCA CCAACATGCT CCTGAATGTC GTGGGCTTCC TGCTGCCCCT GAGTGTCATC ACCTTCTGCA CGATGCAGAT CATGCAGGTG CTGCGGAACA ACGAGATGCA GAAGTTCAAG GAGATCCAGA CGGAGAGGAG GGCCACGGTG CTAGTCCTGG TTGTGCTGCT GCTATTCATC ATCTGCTGGC TGCCCTTCCA 5 GATCAGCACC TTCCTGGATA CGCTGCATCG CCTCGGCATC CTCTCCAGCT GCCAGGACGA GCGCATCATC GATGTAATCA CACAGATCGC CTCCTTCATG GCCTACAGCA ACAGCTGCCT CAACCCACTG GTGTACGTGA TCGTGGGCAA GCGCTTCCGA AAGAAGTCTT GGGAGGTGTA CCAGGGAGTG TGCCAGAAAG GGGGCTGCAG GTCAGAACCC ATTCAGATGG AGAACTCCAT GGGCACACTG CGGACCTCCA TCTCCGTGGA ACGCCAGATT CACAAACTGC AGGACTGGGC AGGGAGCAGA CAGTGAGCAA ACGCCAGCAG GGCTGCTGTG AATTTGTGTA 10 AGGATTGAGG GACAGTTGCT T ATGTTCTCTC CCTGGAAGAT ATCAATGTT CTGTCTGTTC GTGAGGACTC CGTGCCCACC ACGGCCTCTT TCAGCGCCGA CATGCTCAAT GTCACCTTGC AAGGGCCCAC TCTTAACGGG ACCTTTGCCC AGAGCAAATG CCCCCAAGTG GAGTGGCTGG GCTGGCTCAA CACCATCCAG CCCCCCTTCC TCTGGGTGCT GTTCGTGCTG GCCACCCTAG AGAACATCTT TGTCCTCAGC GTCTTCTGCC TGCACAAGAG CAGCTGCACG GTGGCAGAGA TCTACCTGGG GAACCTGGCC GCAGCAGACC TGATCCTGGC CTGCGGGCTG 15 CCCTTCTGGG CCATCACCAT CTCCAACAAC TTCGACTGGC TCTTTGGGGA GACGCTCTGC CGCGTGGTGA ATGCCATTAT CTCCATGAAC CTGTACAGCA GCATCTGTTT CCTGATGCTG GTGAGCATCG ACCGCTACCT GGCCCTGGTG AAAACCATGT CCATGGGCCG GATGCGCGGC GTGCGCTGGG CCAAGCTCTA CAGCTTGGTG ATCTGGGGGT GTACGCTGCT CCTGAGCTCA CCCATGCTGG TGTTCCGGAC CATGAAGGAG TACAGCGATG AGGGCCACAA CGTCACCGCT TGTGTCATCA GCTACCCATC CCTCATCTGG GAAGTGTTCA CCAACATGCT 20 CCTGAATGTC GTGGGCTTCC TGCTGCCCCT GAGTGTCATC ACCTTCTGCA CGATGCAGAT CATGCAGGTG CTGCGGAACA ACGAGATGCA GAAGTTCAAG GAGATCCAGA CGGAGAGGAG GGCCACGGTG CTAGTCCTGG TTGTGCTGCT GCTATTCATC ATCTGCTGGC TGCCCTTCCA GATCAGCACC TTCCTGGATA CGCTGCATCG CCTCGGCATC CTCTCCAGCT GCCAGGACGA GCGCATCATC GATGTAATCA CACAGATCGC CTCCTTCATG GCCTACAGCA ACAGCTGCCT CAACCCACTG GTGTACGTGA TCGTGGGCAA GCGCTTCCGA AAGAAGTCTT 25 GGGAGGTGTA CCAGGGAGTG TGCCAGAAAG GGGGCTGCAG GTCAGAACCC ATTCAGATGG AGAACTCCAT GGGCACACTG CGGACCTCCA TCTCCGTGGA ACGCCAGATT CACAAACTGC AGGACTGGGC AGGGAGCAGA CAGTGAGCAA ACGCCAGCAG GGCTGCTGTG AATTTGTGTA AGGATTGAGG GACAGTTGCT T GCCCTTCAAA GATGAGCTGT TCCCGCCGCC ACTCCAGCTC TGGCTTCTGG GCTCCGAGGA GGGGTGGGGA CGGTGGGGAC ATCAGGCTGC CCCGCAGTAC CAGGGAGCGA CTGAAGTGCC CATGCCGCTT GCTCCGGAGA AGGTGGGTGC 30 CGGGCAGGGG CTGCTCCAGC CGCCTCACCT CTGCTGGGAG GACAAACTGT CCCAGCACAG AGGGAGGGAG GGAGGGCAGG CAGCGGGGAG AAGTTTCCCT GTGGTCGTGG GGAGTT GCCCTTCAAA GATGAGCTGT TCCCGCCGCC ACTCCAGCTC TGGCTTCTGG GCTCCGAGGA GGGGTGGGGA CGGTGGTGAC GGTGGGGACA TCAGGCTGCC CCGCAGTACC AGGGAGCGAC TGAAGTGCCC ATGCCGCTTG CTCCGGAGAA GGTGGGTGCC GGGCAGGGGC TGCTCCAGCC GCCTCACCTC TGCTGGGAGG ACAAACTGTC CCAGCACAGA GGGAGGGAGG 35 GAGGGCAGGC AGCGGGGAGA AGTTTCCCTG TGGTCGTGGG GAGTr GAGCTCTTCA ATATTTTAGT GAAAGCTATA GATGAGGCTC CATAGGGGAT AAAGCACAGA CACACCTTTT CAGAGGGCTT GTGGACTCTG GGCAGCCTGT CCATAGACCT CTGTCCCCAA CTGGCAAGTC AGGAAACTCC AGATTAAGGA GCCCCAATGT GGTTGAACAG CCAGGTGCAC AGATGAGTCA ACCACACAGC CAGGCCAGGG AGGGCCTTCA CTCAAGAGCC TACAGCCAGT TCACAGCCAA GCCAGGGCTA GCGCCAGGCC ACCCATAAAC TGATCTGAGA CTCTGTTTCC 40 CTGTCTCCAT GATGATGGGA TCAGGCTTGA TTGCTGGTTT GTAGGCTTGT TATGAATCAA GTCACAGGGA AGAGGAGCTG ATGGGCTGGG GGGACGTCCT CTGGCCCTCC TGTCTCTTCC CCAGATCCAC TGGGCCCACT CTTATCTGTT CTCTTCTGAA GGAAGGGTTT TAAGGCTTCA AAAAAAAATG 'TTGAAAGT CCCTGCCCTT TCCAGCTCCT ACCGTCTCAG CCCTGGGAGT GTAAAGTGCT GCAGATAGTT AGTAAGTCTT TGAGCAAAAC TGAGAAAGCC AGCCTGAGCC TTGACATGGG AGAAACCTCC GCCATACATC TCCGAAGAAA CGGCCGCGTG 45 TCTCAGGGGA GCGCAAACAC CCGTACCCAG GAAACAGGAC AGCTTCTGCC ACTGTCGCCC TTGGGAGCCG TACGTGGCAT GACAAAGAAA TCCCAGGACT CCGCCTGCCC ACCTGGCCAC CCTCTGTTTA CACCTTCCGC GTAAACGCCC ACTGTTTACA TCCAAAACTC AGACACAAAA TAACCACCTC AAGAAGATAA ATAATGATAA GAAATAAATG TTACGCGAGG CAAATTTATT CACATGGGGC TTCCCAGGCC ACTTTGTGGT CAGCCGGGAG GGACGTTTTT GCCGTCCCAC GACTCCAACG GGCAGCCGGG CCTACGCAAA CATGGAAATC TTCCAAGAGC 50 CTCCCTGGCC CCCAGGGCTC AGAGGGTGGC AGAGCGGAGA GCGAAGGTGG CCGCAGCCTT CCCGGCCCCA CAGCCAGCCT GGCTCCAGCT GGGCAGGAGT GCAGAGCTCA GCTGGAGGCG AGGGGGAAGT GCCCAGGAGG CTGATGACAT CACTACCCAG CCCTTCAAAG ATGAGCTGTT CCCGCCGCCA CTCCAGCTCT GGCTTCTGGG CTCCGAGGAG GGGTGGGGAC GGTGGTGACG GTGGGGACAT CAGGCTGCCC CGCAGTACCA GGGAGCGACT GAAGTGCCCA TGCCGCTTGC TCCGGAGAAG GTGGGTGCCG GGCAGGGGCT GCTCCAGCCG CCTCACCTCT 55 GCTGGGAGGA CAAACTGTCC CAGCACAGAG GGAGGGAGGG AGGGCAGGCA GCGGGGAGAA GTTCCCTGT GGTCGTGGGG AGTTGGGAAA AGTTCCCTTC CTTCCGGAGG GAGG GAATTCGGGA AAAAGTGAAG WO 00/62736 PCT/USOO/08020 40 GTGTAAAAGC AGCACAAGTG CAATAAGAGA TATTTCCTCA AATTTGCCTC AAGATGGAAA CCCTTTGCCT CAGGGCATCC TTGGCTGG CACTGGTTGG ATGTGTAATC AGTGATAATC CTGAGAGATA CAGCACAAAT CTAAGCAATC ATGTGGATGA TTTCACCACT TTTCGTGGCA CAGAGCTCAG CTTCCTGGTT ACCACTCATC AACCCACTAA TTTGGTCCTA CCCAGCAATG GCTCAATGCA CAACTATTGC CCACAGCAGA CTAAAATTAC 5 TTCAGCTTTC AAATACATTA ACACTGTGAT ATCTTGTACT ATTTTCATCG TGGGAATGGT GGGGAATGCA ACTCTGCTCA GGATCATTTA CCAGAACAAA TGTATGAGGA ATGGCCCCAA CGCGCTGATA GCCAGTCTTG CCCTTGGAGA CCTTATCTAT GTGGTCATTG ATCTCCCTAT CAATGTATTT AAGCTGCTGG CTGGGCGCTG GCCTTTTGAT CACAATGACT TTGGCGTATT TCTTTGCAAG CTGTTCCCCT TTTTGCAGAA GTCCTCGGTG GGGATCACCG TCCTCAACCT CTGCGCTCTT AGTGTTGACA GGTACAGAGC AGTTGCCTCC TGGAGTCGTG 10 TTCAGGGAAT TGGGATTCCT TTGGTAACTG CCATTrGAAAT TGTCTCCATC TGGATCCTGT CCTTTATCCT GGCCATTCCT GAAGCGATTG GCTTCGTCAT GGTACCCTTT GAATATAGGG GTGAACAGCA TAAAACCTGT ATGCTCAATG CCACATCAAA ATTCATGGAG TTCTACCAAG ATGTAAAGGA CTGGTGGCTC TTCGGGTTCT ATTCTGTAT GCCCTTGGTG TGCACTGCGA TCTTCTACAC CCTCATGACT TGTGAGATGT TGAACAGAAG GAATGGCAGC TTGAGAATTG CCCTCAGTGA ACATCTTAAG CAGCGTCGAG AAGTGGCAAA AACAGTTTTC 15 TGCTTGGTTG TAATTGC TCTTTGCTGG TTCCCTCTTC ATTTAAGCCG TATATTGAAG AAAACTGTGT ATAACGAGAT GGACAAGAAC CGATGTGAAT TACTTAGTTT CTTACTGCTC ATGGATTACA TCGGTATTAA CTTGGCAACC ATGAATTCAT GTATAAACCC CATAGCTCTG TATTTTGTGA GCAAGAAATT TAAAAATTGT TTCCAGTCAT GCCTCTGCTG CTGCTGTTAC CAGTCCAAAA GTCTGATGAC CTCGGTCCCC ATGAACGGAA CAAGCATCCA GTGGAAGAAC CACGATCAAA ACAACCACAA CACAGACCGG AGCAGCCATA AGGACAGCAT 20 GAACTGACCA CCCTTAGAAG CACTCCTCGG TACTCCCATA ATCCTCTCGG AGAAAAAAAT CACAAGGCAA CTGTGAGTCC GGGAATCTCT TCTCTGATCC TTCTTCCTTA ATTCACTCCC ACACCCAAGA AGAAATGCTT TCCAAAACCG CAAGGGTAGA CTGGTTTATC CACCCACAAC ATCTACGAAT CGTACTTCTT TAATTGATCT AATTTACATA TTCTGCGTGT TGTATTCAGC ACTAAAAAAT GGTGGGAGCT GGGGGAGAAT GAAGACTGTT AAATGAAACC AGAAGGATAT TTACTACTTT TGCATGAAAA TAGAGCTTrC AAGTACATGG CTAGCTTTTA 25 TGGCAGTTCT GGTGAATGTT CAATGGGAAC TGGTCACCAT GAAACTTTAG AGATTAACGA CAAGATTTTC TACTTTTT AAGTGATTTT TTTGTCCTTC AGCCAAACAC AATATGGGCT CAAGTCACTT TTATTTGAAA TGTCATTTGG TGCCAGTATC CCGAATTC GCCACCATGG AAACCCTG CCTCAGGGCA TCCTTTTGGC TGGCACTGGT TGGATGTGTA ATCAGTGATA ATCCTGAGAG ATACAGCACA AATCTAAGCA ATCATGTGGA TGATTTCACC ACTTTTCGTG GCACAGAGCT CAGCTTCCTG GTTACCACTC ATCAACCCAC TAATTTGGTC 30 CTACCCAGCA ATGGCTCAAT GCACAACTAT TGCCCACAGC AGACTAAAAT TACTTCAGCT TTCAAATACA TTAACACTGT GATATCTTGT ACTATTCA TCGTGGGAAT GGTGGGGAAT GCAACTCTGC TCAGGATCAT TTACCAGAAC AAATGTATGA GGAATGGCCC CAACGCGCTG ATAGCCAGTC TTGCCCTTGG AGACCTTATC TATGTGGTCA TTGATCTCCC TATCAATGTA TTTAAGCTGC TGGCTGGGCG CTGGCCTT GATCACAATG ACTTTGGCGT ATTTCTTTGC AAGCTGTTCC CCTTGCA GAAGTCCTCG GTGGGGATCA CCGTCCTCAA 35 CCTCTGCGCT CTTAGTGTTG ACAGGTACAG AGCAGTTGCC TCCTGGAGTC GTGTTCAGGG AATT1GGGATT CCTT'TGGTAA CTGCCATTGA AATTGCCTCC ATCTGGATCC TGTCCTTTAT CCTGGCCATT CCTGAAGCGA TTGGCTTCGT CATGGTACCC TTTGAATATA GGGGTGGACA GCATAAAACC TGTATGCTCA ATGCCACATC AAAATTCATG GAGTTCTACC AAGATGTAAA GGACTGGTGG CTCTTCGGGT TCTATTTCTG TATGCCCTTG GTGTGCACTG CGATCTTCTA CACCCTCATG ACTGGTGAGA TGTTGAACAG AAGGAATGGC AGCTTGAGAA 40 TTGCCCTCAG TGAACATCTT AAGCAGCGTC GAGAAGTGGC AAAAACAGTT TTCTGCTTGG TTGTAATTTT TGCTCTTTGC TGGTTCCCTC TTCATTTAAG CCGTATATTG AAGAAAACTG TGTATAACGA GATGGACAAG AACCGATGTG AATTACTTAG TTTCTTACTG CTCATGGAT7 ACATCGGTAT TAACTTGGCA ACCATGAATT CATGTATAAA CCCCATAGCT CTGTATTG TGAGCAAGAA ATTTAAAAAT TGTTTCCAGT CATGCCTCTG CTGCTGCTGT TACCAGTCCA AAAGTCTGAT GACCTCGGTC CCCATGAACG GAACAAGCAT CCAGTGGAAG 45 AACCACGATC AAAACAACCA CAACACAGAC CGGAGCAGCC ATAAGGACAG CATGAACTGA CCACCCTTAG AAGCACTCCT GAATTCGGGA AAAAGTGAAG GTGTAAAAGC AGCACAAGTG CAATAAGAGA TATTTCCTCA AATTTGCCTC AAGATGGAAA CCCTTTGCCT CAGGGCATCC TTTGGCTGG CACTGGTTGG ATGTGTAATC AGTGATAATC CTGAGAGATA CAGCACAAAT CTAAGCAATC ATGTGGATGA TCACCACT TTTCGTGGCA CAGAGCTCAG CTTCCTGGTT ACCACTCATC AACCCACTAA TTTGGTCCTA CCCAGCAATG GCTCAATGCA 50 CAACTATTGC CCACAGCAGA CTAAAATTAC TTCAGCTC AAATACATTA ACACTGTGAT ATCTTGTACT ATTTCATCG TGGGAATGGT GGGGAATGCA ACTCTGCTCA GGATCATTTA CCAGAACAAA TGTATGAGGA ATGGCCCCAA CGCGCTGATA GCCAGTCTTG CCCTTGGAGA CCTTATCTAT GTGGTCATTG ATCTCCCTAT CAATGTATTT AAGCTGCTGG CTGGGCGCTG GCCTTTTGAT CACAATGACT TTGGCGTATIT TCTTTGCAAG CTGTTCCCCT TTTTGCAGAA GTCCTCGGTG GGGATCACCG TCCTCAACCT CTGCGCTCTT AGTGTTGACA 55 GGTACAGAGC AGTTGCCTCC TGGAGTCGTG TTCAGGGAAT TGGGATTCCT TITGGTAACTG CCATTGAAAT TGTCTCCATC TGGATCCTGT CCTT7ATCCT GGCCATTCCT GAAGCGATTG GCTTCGTCAT GGTACCCTTT WO 00/62736 PCT/USOO/08020 41 GAATATAGGG GTGAACAGCA TAAAACCTGT ATGCTCAATG CCACATCAAA ATTCATGGAG TTCTACCAAG ATGTAAAGGA CTGGTGGCTC TTCGGGTTCT ATCTGTAT GCCCTTGGTG TGCACTGCGA TCTTCTACAC CCTCATGACT TGTGAGATGT TGAACAGAAG GAATGGCAGC 'TrGAGAATTG CCCTCAGTGA ACATCTTAAG CAGCGTCGAG AAGTGGCAAA AACAGTTC TGCTTGGTTG TAATITTTGC TCTTTGCTGG 'JTCCCTCTTC 5 AITrAAGCCG TATATT1GAAG AAAACTGTGT ATAACGAGAT GGACAAGAAC CGATGTGAAT TAC~rAGm~ CTACTGCTC ATGGATTACA TCGGTATrAA CTT1GGCAACC ATGAATTCAT GTATAAACCC CATAGCTCTG TNITIGTGA GCAAGAAAT[ TAAAAATTGT TCCAGTCAT GCCTCTGCTG CTGCTGTTAC CAGTCCAAAA GTCTGATGAC CTCGGTCCCC ATGAACGGAA CAAGCATCCA GTGGAAGAAC CACGATCAAA ACAACCACAA CACAGACCGG AGCAGCCATA AGGACAGCAT GAACTGACCA CCCTITAGAAG CACTCCTCGG TACTCCCATA 10 ATCCTCTCGG AGAAAAAAAT CACAAGGCAA CTGTGAGTCC GGGAATCTCT TCTCTGATCC TTC TTCC FTA ATTCACTCCC ACACCCAAGA AGAAATGCTT TCCAAAACCG CAAGGGTAGA CTGGTTTATC CACCCACAAC ATCTACGAAT CGTACTITCTT TAATTGATCT AA ITTACATA TTCTGCGTGT TGTATTCAGC ACTAAAAAAT GGTGGGAGCT GGGGGAGAAT GAAGACTGTT1 AAATGAAACC AGAAGGATAT TTACTACTTT TGCATGAAAA TAGAGCTTTC AAGTACATGG CTAGCTTrA TGGCAGTTCT GGTGAATGTT CAATGGGAAC TGGTCACCAT 15 GAAACTTTAG AGATTAACGA CAAGATTTC TACTTT= AAGTGATT 1TTTGTCC FTC AGCCAAACAC AATATGGGCT CAAGTCACTT TTrA'TTGAAA TGTCATMGG TGCCAGTATC CCGAAF-FC AACAAGAAAA GCGTTGGTAG CTCTGGTGAA TCCCAAAAGA ATGTGGCAGT TGCTAGCCAT GCTCCTGAAT ATGTATAAAC AGTACATCAT ATGACTAAGA GMTGACTTA GGGGTTAGAT 2TTATGTGTr TGAACCCCAA ATTAGT7ATT TAATAGJ'TGG CACCCCAAAA CAAGTTACTT AACCTCACTA AGG'JTCAGTF TTCCTGTITA TAAAATGTAG 20 ATAGTGATAG TATGTACTTT ATAGGATI1AT TGTGAAAAAT'AAATGAAATA TCAGA=TAT TTAGGATAAC ACCTGGCATA TGTTTGGTAT TCAGAATTAG 'ITGCTGCTGT TFITATTCTGC TCTCCCTTGC ATCCCACTIT TCTAAGY7GT AAACTAAATA GTTGTACACA GATTGACAGA TTAAGAAAGG CTTGTGATTG TGCTAGACCT ATGCCTATGC CTCTGTCTCA CCAGATTCCA GGTGTATATG TGGAGGTGGG ATAGGGAGTG GAGTAAGTGG GTAAATAYI'A AATI'GCCCAG TTGGGCACCA TCCTGAATAT TATCTCTAAA GAAAGAAGCA AAACCAGGCA 25 CAGCTGATGG GT-rAACCAGA TATGATACAG AAAACATrTC CTrCTGC'Tr TTGGT'TAA GCCTATAM~ GAAGCCTTAG ATCTCTCCAG CACAGTAAGC ACCAGGAGTC CATGAAGAAG ATG GATCTTCATG3 TGGAATGACT GG'TrCAT7C AATAGACT11A ATTCAGCAGT CTGTGGGGAA GAGCAAGGTA TGATAGAATG GT'TCCTCAAG TGCTTCAGAT GTGAAGTGGG 'ITTAAATATA CTGTCCCTGT CTCTTCAGA GTI'TTGGTAA AGATAAAATA GGACACTCAT TTAAAAGCAA TC1TJTGCAAA TGACAAGCCA CTATAGACAT TAATAGAGTr 30 'ITCATICCA GTATrATCAT TAATATCAGA TCCTGGAAGA AGGTTGAGCC TTGACCTAGA GCAAAAAAAC AGAAGAATTA GTAAAGGAAT CCTGGAGAAA GCCCCTGCTG TGTATTTAAA GGAGAAAGGG AGATCATGT GGGAAATTAT AATATTAAAA GTAAACAAAA GCTAGGAAGT AAAATAAAAT AAATTATATG GCCTAGATCC CCATAAGTAA TGGYIAACT TCTGCC'I1CC TGTGTTCTGA GCCAGATTAG GGCACAGTAG AGAAAGAGGA GTCTCTGAAA ATGTI'TCCAA 'ITCGCTGGT CAGACAGCGG ATCATCAGTG AATCAGATGA AAAYJTGTGG 35 A'I=ATGCAC TAACTGATCA GCAGGAAATT AAACAAGAAA AGCGTrGGTA GCTCTGGTGA ATCCCAAAAG AATTTGGCAG TTGCTAGCCA TGCTCCTGAA TATGTATAAA CAGTACATCA TATGACTAAG AGTTTGACTT AGGGGTT~AGA TITATGTGT 'ITGAACCCCA AATTAG'ITAT TTAATAGTTG GCACCCCAAA ACAAGTTACT TAACCTCACT AAGATTCAGT TTTCCTGTT ATAAAATGTA GATAGTGATA GTATGTACTT TATAGGATTA TTGTGAAAAA TAAATGAAAT ATCAGATTTA 1TTTAGGATAA CACCTGGCAT ATG IGGTA TTCAGTAATT 40 AGTTGCTGCT G'rTrATTCT GCTCTCCCTT GCATCCCACT LTTCTAAGTT GTAAACTAAA TAGTTGTACA CAGATTGACA GATTAAGAAA GGCTTGTGAT TGTGCTAGAC CTATGCCTCT CTCTCACCAG ATTCCAGGTG TATATGTGGA GGTGGGATAG GGAGTGGAGT AAGTGGGTAA ATATTAAA'rr GCCCAGTTGG GCACCATCCT GAATA'ITATC TCTAAAGAAA GAAGCAAAAC CAGGCACAGC TGATGGGTTA ACCAGATATG ATACAGAAAA CATI1TCCTT1C TGCTITGG TITI7AAGCCT ATA ITFGAAG CC'ITAGATCT CTCCAGCACA GTAAGCACCA 45 GGAGTCCATG AAGAAGATGG CTCCTGCCAT GGAATCCCCT ACTCTACTGT GTGTAGCC'I1 ACTGTTCT-rC GGTAAGTAGA GA'I1CAA L1A CCCCTCCCAG GGAGGCCCAA ATGAA'TrGG GGAGCAGCTG GGGTAGGAAC CTI1?ACTGTG GGTGGTGACT TITCTAGGA CATGTGCAAA CTAITTGGGCA TITCCCAGGG ACTCTGTAGT GGAGCCAAGC TAGAAAGCAG AGGCAAGTGG GCTGAGCAAC ACCTAAGGAG GAAGCCAGAC TGAAAGCTTG GTTCCT17GCA 'TTTGCTCTGG CATCTI7CCAG AGTGCAAATT TCCTACCAAG GTAATGAGGG TAGAGGAGAG 50 AAAGAAGCTC 'ITTCTrCCCC TGATTCTCAT TCCTGAAAAG ACGGTrGGTC CTTA AAATTC CATGGATGTA GATCTTATCC CCACACCCAG ATJTCTAGTCC TCTGGAGATA AAGAAGACTG CTGGACACTA ATGTATCCTC TCTGGACT'r TGCAGCTCCA GATGGCGTGT TAGCAGGTGA GTCCTCTG'IT CTTFCCCT TGGTGTATCA ACATGTCTGG GCATTGCTTT CCTCTCACTA 'I1TTrCGT CCCATCACT11 CTGC'TrTCTA ATGAGCATGA ATCTGT-rCCT TGGCCAGACT ACTTTCCCTC TCCACCTFGC CTFGTCTTC TITITITCCC TGATTCAT-fG 55 CATTCTCTCA AGTCATTCTC TCCTCTGITTT TAGTCAATAA CCATGTCTGT TGCACATATA CATGTCTCAT TCTCTCTCCT AGACAC'JTTG GCATGATCTC GCTCAATAAT TACA FTA FA TTATTATFGC CATTTTATAA WO 00/62736 PCT/USOO/08020 42 TTGAGGATGC TGAAACTCAG TGATI=CTG GTGGTTACAT GGCTAAGGAA CTGGA'TrTCA ACGTAAGTTC CTTGGATCTA AGTCCAGT11C TCTTCTGACT ATATCACCCT TTTGTTATCA CCATGTATCT ACflCThTGG TCTCTG'I1CA AA=IIGCACT ACATCCCCTT GTTCCAGGAA GCCATTCAAG ACTGAC1TC TTAGTGCCTC TCACTACTT7 CTGGAACTGA CATATGYIT TCACTCTGTA TATACTTACA ATTAAATAGT CATAAATATr 5 CAGAGCTrGG AGAAACCTTA TA'1TCATCC AGTCCAGTAA ATTTATCCAT CCATAATrCA CTCArrCATTr CACATAATAA ATAFI1AATG TAACAATGGT TGAACATGGC AGACAGTGTT TCTACCTCAA AAGAGATTGC AGTCCTCATT TACAGATACT GAATTGAAAT TAACAGAAGT AGAGTGAGTC AGCTCAAATC ACATAGTGAA 'rrGGTTTCTT TGYTTAAA TCTCCTGCAT ATGTGTCCTG TCTrCTCCC TGTGTTGGGC GTTCCCTGGG GCACCAATAC TAATYrCTCC 'FrCCCCTAGA AATCAAAACA GGGTCTTATC ACCAACAGAA TAAGGACAGG 10 TTGACCACTG ATTGTCAGAA TATFGCTTCG =TGTACrrr TAAGCCTAGA CAG=FTCAA TGACTT1T TCTCTCTACA TGTCTTTTCA TATTITATC ITCTTGAAGT CCCTCAGAAA CCTAAGGTCT CCTTGAACCC TCCATGGAAT AGAATA'ITTA AAGGAGAGAA TGTGACTCT= ACATGTAATG GGAACAA'ITT CYL17GAAGTC AGTTCCACCA AATGGTTCCA CAATGGCAGC C1TTCAGAAG AGACAAATFC AAGTTTGAAT APJ7GTGAATG CCAAAMTGA AGACAGTGGA GAATACAAAT GTCAGCACCA ACAAGTTAAT GAGAGTGAAC CTGTGTACCT 15 GGAAGTC'I1C AGTGGTAAGT TCCAGGGATA TGGAAATACA GATCTCTCAT GTGAGGGATG GCTCATCTGA AGATGGGAAA AAACAGGTTA TTCCAAGGGT TAGGACACCA GAGTGGGATI' CAAGGCCTCT CNITTTAAG ACCCCTGCAT TGGCTGGGCA CAGTGGCTCA CGCCTGTAAT CCCAGCACT11 TGGGAGGCTG AGGCAGGTGG ATCACGAGGT CAGGAGATCG AGACCATCCG GCTAACATGG TGAAACCCCA TCTCTGCTAA AAAATATATA TATATAAAAT TAGCCGGGCG TAGTGGTGGG CACCTGTAGT CCCAGGTACT CGGGAGGCTG AGGCAGGAGA 20 ATGGTGTGAA CCCAGGAGGT GGAGG I1GCA GTGAGCTGAG ATCACGCCAC TGCCCTCCAG CCTGGGCTAC AGAGCAAGAC TCCGTCTCAA AAAATAAATA AATAAATAAA AAAGACCCCT GCATCTCIT TC ITCTACCC CCTTCCCTr TGATTACTTG TATGCCTCT TTCAATATTC TAGTCATCTC TCAATATTAT TCCTCCACCC TATJTCCTC TATCTTCT GCCTAGATTC AGGTATATAT TATGTGGTCA AACAGCATGA CATATATGTG AACATrTCAA AGAGCTGTGT ATCTGGAATA GGATCAAAAG GTT7GACTTA AAGYITTGCT CTGCATAATC 25 CATATGGCAG GACCTGAATA TTAGGTTGTA CTCTTCGTTA TGAAACATAT CTGGGTACAT YTCCTFATGT CCTCTGT7GT TACTTAAGAA CACATATIC ATGCTFGTIT CATITATC ACTCCTACTG CCAACAAATA GCATAGCATG CTTAGGCACA TGTGGC'ITAA TTAGCAAATG TTGAATAAAC AAATrAATGA TVGAATAG TGACCAATAG GTCTCTTTA TACTCTATAT TTTTCTCTT1G AGTGAAAAAA AATG'ITTCAA CCTCCATATG TAAATI'CCAA ACACAAACTA AAGCAATGTA GAATAGCTI'C 'ITTATTCCCT GGAGTAGGTr CTAGAGAAGT 30 CCTAAAGGAT TGGTCCTAAA TTAAFrATGC TTATTATGCT AGCGATA TT CC'TrTCAAAA TTCTCC'ITTA ATGAATGCTI1 TrAATTTTT ACAAAAGCAT TAACCATAGA ATGTGATrCT TGTCTITCAC TGACTCArrTA GTGACAAATA YI1GTT1GAGT ACCTACCAAC TCCTAAGTAT TGCTACCAAC TCCTAAATAC TGTGFTGGGC ATTCAGAATA GAATGTAGAA CTAGACAGGG TCCCTGACTT CTTGGAGCAC AGAGCAGTAT GGGAAGAGGA CATTAAATAA AGAATTACAT AAGTAATTAA TrTAAAMTAT ACATG'rT=G AAGAAGTIT =~GACAA 35 CTATAATTAA CACTAGAACT GGGAAGTC TATAAGGTAA GAGAGGACAA AATAGACACT CTCCTAAGCT AAAATTCCCA AGAAAGACTG TI17ATITTCC CCTAACTAAC TAGAACTAGC AACAGAAGAT CTGAAAGGAA TrCTGGC'I= CAAGTGTTCC ATGTATGGAC TCATCAGGGA GGTCCGAGAG GC'ITTGTGGC CCCAGACTGA C'T=1CAGGA GGGGAAAGGA TTTATCAATA CACAAGACAG GCTCTAAGCA TTATrrrGTG CCCITTrAAAA ATCCACTTA TGAGCCAAAA AGTGAGTAA TGATAATTCA TAGThrCTGA CACATGCTCT ATGCGTGGCT 40 CTCTI'TTCTC TATTCATTCT CTCTCTCTT1C A'ITTATTGTT AAATAAATAA TGTAATGAAT GYFCTTCAGA CTGGCTGCTC CTTCAGGCCT CTGCTGAGGT GGTGATGGAG GGCCAGCCCC TCTT1CCTCAG GTGCCATGGT TGGAGGAACT GGGATGTGTA CAAGGTGATC TATTATAAGG ATGGTGAAGC TCTCAAGTAC TGGTATGAGA ACCACAACAT CTCCATTACA AATGCCACAG TTGAAGACAG TGGAACCTAC TACTGTACGG GCAAAGTGTG GCAGCTGGAC TATGAGTCTG AGCCCCTCAA CATTACTGTA ATAAAAGGTG AGYI7GGTAAA GGAAAGGAAA 45 AGCATCCATA GCAGGGGAAG GAAGAGAGAA CTTCTGAGCC TGAGCAGTTG CAGCTTGTAG AAGGGGGGCA CCTGTGATAC ACTGGAAAGC CTACCAGACT TGCAATGAGG AGACCTGGGT GATAGTATAT ATCTCAATCT CTGTTTCAAA GCCTTGACTT GTFAAATGGT GATAGTAATA CCTGCTTGCA CTATGAAA T ITrATGAAGA TTAATGTGGT AATATITGTG AAATGACI= GTAAACTGTT AAGCACTACC CAAGCATAAC AGATTGTGAT TACTATrTG ATCTCAAAGT CATCTG FTGC TCCTGGGGGA ACACTTATAT TI'ATCAAATfl GAAAAAAAGT 50 TTCAAAGTTG AATGAAGAAA GGATATAAAG AGCTTGAGGA GCCCATCCA GCTTAGGAGG GCTGGGAAAG GAAACCAGCA AGTCAGTAAG CTGTGTGCCT GTGTATTGAG GGAGGAGGGA ATGGAC'TrGA TATGGAGAGG GTAGGGAGGT GGACTGCCTC TATGGCCTGT AAGAAAAACT GCTCTCTCCA AACTCTTTAT AAGAGAGGGA GCCTGTGAAG TATTCACTr TGAAGGAGAA AGTI7AGACTr TTCCTTCACA CACTTTGTAC ATAATAATGT TTAAAAAAGC ATGAGGTCAA AATACATAAT TAAGTCCTAG CAGTTrCTCTG TTAACTAATT TGAGACTGAA 55 GTGCTATGTA CTI1GTCTCTA GGCTI1CCAGT ATCTTCATCT GTAAAACAGA ATATPTGGTC TAGAYFCCAT TAGAATCATI' TGATAACIA AAAAATATAT TGATGCTCAT GTCTCA'ITTC 'GAGATTCT GATTTAATTG WO 00/62736 PCT/USOO/08020 43 GTTTGGGGTG CAGCCTGGGT ATACGTAT TTCATAGGTC 'ITCACATAA TGGTAATGGG TAGCCAATAT TGAGAATCAC 'rTGTCTAGGT GATCITTTAAA TGATFTCTGG ATGTAATATT CTGAGGCTCT ATAATTTGAG ACTAATCACA AAAATCGGTA CAG'TrATAA ACAGACTAAC AGAACCACAA. AATAATAGAA TTGGAAGGCA A'ITTAACTAG TGCAA'TrTCT TCA'T=rGCC TAACAGGCAT GTAAGAAATG ATGATI7GATT GAGTAATAGG 5 CATTGATGAC CCCTGTCCTC Ac'LTrGTCCC CTTTCCACCC CTI1AATTATA TGTGAAT7CT GGTCTTGTCA TTTCGAATAA GGGG TTATC TTTCCTATTG TCT-rCCCCTC TGGGCACGGC ACACTGGCTA CTGGAG'ITAA GAGGAAATGC TTAGGACTCC CTGTGGCTCC AGGGAGCACC AACAGAGCAA CTCAACCTAG TGTTAATCTG AGTGTI1TTCT CTGTGCTTCT GGATGCCACA TCACGCTAAA AATGAAGGAC AAAGCTTGGT CTTTCTC3TA GGGAGGATGA AACTCTGAAC CTCATI1TC AGTTCCCAAG ATGAAT~rATG T11TCTCATTG CATCTGTGTT 10 CCACTACAGC TCCGCGTGAG AAGTACTGGC TACAA'TT11 TATCCCAT1TG I1GGTGGTGA rrCTGFITGC TGTGGACACA GGATTATrA TCTCAACTCA GCAGCAGGTC ACATTTCTCT TGAAGATTAA GAGAACCAGG AAAGGCTTCA. GACTrTCTGAA CCCACATCCT AAGCCAAACC CCAAAAACAA CTGATATAAT TACTCAAGAA ATA'TrGCAA CA VrAG'I= TTTCCAGCAT CAGCAATTGC TACTCAATrG TCAAACACAG CTTGCAATAT ACATAGAAAC GTCTGTGCTC AAGGA'ITTAT AGAAATGCTT CATTAAACTG AGTGAAACTG GTTAAGTGGC 15 ATGTAATAGT AAGTGCTCAA TTAACATTGG TTGAATAAAT GAGAGAATGA ATAGA,17CAT TTATTAGCAT TTGTAAAAGA GATG'rTCAAT TTCAATAAAA TAAATATAAA ACCATGTAAC AGAATGCTrC TGAGTATTCA AGGCTFGCTA G1T7GTTTGT TTGTITTTCTA CTAAAGGCAA GGACCATGAA GTTCTAGATT GGAAATGTCC TCTCTTGACT ATrGCAAGTG CGATCTAGGA ATGAAAAGAC ATAGGAGGAT GCCAGTGAGG TGGATCAITTT TTATGCTTCT TCTTCAGCTT ACTAAATATG AACTrCAGT TC'I17GGCAGA ATCAGGGACA GTCTCAAGAC 20 ATAGGACTCT CAGGATGAAG TAGAGTCCAG GATTCCTCTG TGATTGTTT GCCCCTCCCA AATTTATATC TrGAAC'flAT GTCTTGTATC TTfIATACAGC ACCTGAACCA AGCATITGG AGAAATTCCA GCTAATAATA ATAACCAAAA CCTTCGGCTC TGAAAACAGT CCAGGACTGA ATAAGATCITF GGGCAAAAGA ACTAGACAGT TTTGGMfAT TITCCCTITC A=FTATGTC TTCATCATAG TCATGGAGG CTCA'rrCTrC TTGTCATGGA GTAAATGGGA TTAAAG'ITC TACTAAGAGT CTCCAGCATC CTCCACCTGT CTACCACCGA GCATGGGCCT 25 ATATrGAAG CCTT1AGATCT CTCCAGCACA GTAAGCACCA GGAGTCCATG AAGAAGATGG CTCCTGCCAT GGAATCCCCT ACTCTACTGT GTGTAGCCTT ACTG I1CTT1C GCTCCAGATG GCGTGTTAGC AGTCCCTCAG AAACCTAAGG TCTCC'I7GAA CCCTCCATGG AATAGAATAT 'ITAAAGGAGA GAATGTGACT C'ITACATGTA ATGGGAACAA TITC'ITTGAA GTCAGTTCCA CCAAATGGTT CCACAATGGC AGCCTITCAG AAGAGACAAA TTCAAGTG AATATI'GTGA ATGCCAAATT TGAAGACAGT GGAGAATACA AATGTCAGCA CCAACAAGTT 30 AATGAGAGTG AACCTGTGTA CCTGGAAGTC TTCAGTGACT GGCTGCTCCT TCAGGCCTCT GcTGAGGTGG TGATGGAGGG CCAGCCCCTC TTCCTCAGGT GCCATGGITG GAGGAACTGG GATGTGTACA AGGTGATCTA TTATAAGGAT GGTGAAGCTC TCAAGTACTG GTATGAGAAC CACAACATCT CCNVFACAAA TGCCACAGTT GAAGACAGTG GAACCTACTA CTGTACGGGC AAAGTGTGGC AGCTGGACTA TGAGTCTGAG CCCCTCAACA TTACTGTAAT AAAAGCTCCG CGTGAGAAGT ACTGGCTACA AYTT=ATC CCATTGTTGG TGGTGATTCT 35 G=~GCTGTG GACACAGGAT TA'T7ATCTC AACTCAGCAG CAGGTCACAT ITCTCTTGAA GATTAAGAGA ACCAGGAAAG GCTT1CAGACT TCTGAACCCA CATCCTAAGC CAAACCCCAA AAACAACTGA TATAATI'ACT CAAGAAATAT TTGCAACATT AGTTFIT=C CAGCATCAGC AATYFGCTACT CAATTGTCAA ACACAGCTTG CAATATACAT AGAAACGTCT GTGCTCAAGG A ITATAGAA ATGCTTCATT AAACTGAGTG AAACTGGTrTA AGTGGCATGT AATAGTAAGT GCTCAATTAA CATTGGTTGA ATAAATGAGA GAATGAATAG ATTCATTTAT 40 TAGCATTTGT AAAAGAGATG TTCAA M CA ATAAAATAAA TATAAAACCA TGTAACAGAA TGCTTCTGAG TAAAAAAAAA AAAAAAAAAA. AAAAAAAA TCTCAATATA ATAATATTCT TTATTCCTGG ACAGCTCGGT TAATGAAAAA ATGGACACAG AAAGTAATAG GAGAGCAAAT CTTGCTCTCC CACAGGAGCC 'FrCCAGTGTG CCTGCATTG AAGTCTI1GGA AATATCTCCC CAGGAAGTAT CTTCAGGCAG ACTATTGAAG TCGGCCTCAT CCCCACCACT GCATACATGG CTGACAGYI17 TGAAAAAAGA GCAGGAGTTC CTGGGGGTAA CACAAAT1?CT 45 GACTGCTATG ATATGCCT GT'LTGGAAC AGTTGTCTGC TCTGTACTTG ATATITCACA CATTGAGGGA GACATTTT CATCA'TrAA AGCAGGTI'AT CCATT1CTGGG GAGCCATA'IT 'TTrCTA'rr TCTGGAATGT TGTCAATTAT ATCTGAAAGG AGAAATGCAA CATATCTGGT GAGAGGAAGC CTGGGAGCAA ACACTGCCAG CAGCATAGCT GGGGGAACGG GAATI'ACCAT CCTGATCATC AACCTGAAGA AGAGCP-rGGC CTATATCCAC ATCCACAGTT GCCAGAAATT TTTTGAGACC AAGTGCTfTA TGGCTTCCTT TTCCACTGAA ATTGTAGTGA 50 TGATGCTGTT TCTCACCATI? CTGGGACTI7G GTAGTGCTGT GTCACTCACA ATCTGTGGAG CTGGGGAAGA ACTCAAAGGA AACAAGGT7C CAGAGGATCG TGTrATGAA GAATTAAACA TATA'VrCAGC TAC'ITACAGT GAGTTGGAAG ACCCAGGGGA AATGTCTCCT CCCATTGATT TATAAGAATC ACGTGTCCAG AACACTCTGA TI7CACAGCCA AGGATCCAGA AGGCCAAGGT CT7GTTAAGG GGCTACTGGA AAAATTT1CTA TTCTCTCCAC AGCCTGCTGG TTTT AAGCT=TCA AAGGTGCAAT TGGATAACTT CTGCCATGAG AAATGGCTGA 55 ATTGGGACAC AAGTGGGGAC AATrCCAGAA GAAGGGCACA TCTC'TT7CT TTCTGCAGTT CTTTCTCACC TTCTCAACTC CTACTAAAAT GTCTCAT1T CAGGTrCTGT AAATCCTGCT AGTCTCAGGC AAAATTATGC WO 00/62736 PCT/US00/08020 44 TCCAGGAGTC TCAAA'II7C TI'A'TI'CATA TTAGTCTTTA ITrAGTAGAC TTCTCAAETT 'rrCTA'rrCAT CACAAGTAAA AGCCTGTI7GA TCTTAATCAG CCAAGAAACT TATCTGTCTG GCAAATGACT TATGTATAAA GAGAATCATC AATGTCATGA GGTAACCCAT TTCAACTGCC TATTCAGAGC ATGCAGTAAG AGGAAATCCA CCAAGTCTCA ATATAATAAT ATFCTIATT CCTGGACAGC TCGGITAATG AAAAAATGGA CACAGAAAGT 5 AATAGGAGAG CAAATCTI'GC TCTCCCACAG GAGCCTrFCCA GGTAGGTACA AGGTATTATT TITICTACC CTCAGTCACT TGTGGCAGGG GAAGTCATAG TCACGGTGCT TAGGAGATGA AACTITATTG ATTTAGGCAT GGATCCATCT AGTTAA1?A ATATATTGGG TATGAGGAAG CTACTTGCTG TAQTTCCAT GTGGTTCTCT CTCCCTGGAG AGGAACA'Tr TTACTCAGCT TGCAAACTGG AAATAGATI TCTCACA'ITA GAAGCTCATT TTCTGGGTAT GAGACAGGAG AGTTCATACT GTGTATGTAG ATCTCTGGCT TCTGGGTCTG ACATGTGCTG 10 AGGGACACAT ATCC FTCACA CATGC3TIA TAAATACTTG ATAAAGTAAC CTGCTrc'ITG ATTGGTCTI1 ATAATCCATA AGCTGTGGGA TGCTTCTCTG AAGATGAAAA TAGTAATAGA GTCCCATCTA GCTATTCAAA GCCATrCCPT CATTGTATTC TGTGCACATG AAGrTGGGGT TTGTTACTGA CAAAATATAT TCAGATACAT 'ITCTATGTTA AAAGGATTGT GAGATGCATA GGTAAATGTG ITrATTTTCA G'ITTACTTG TCAACATAGA TGAATGAGAA AGAACTTGAA AGTAACACTG GATTAAGAAT AGGAAAA'TrT GGCATGGA'T 'FrGCTCCATrr 15 TTGTCCCATC TAATCACTrG GATAGTGTTC AGGTG'ITC'r GGTCAGTTAC TTGGATGCTC TGAGCFPTAG TJTCTrGGTG ATTACAATGA AGATTTGAAT TACAGGATGG CTGAAAAA ATAAACAAAA CTCCCCTTTC TGTCTGTCGA GAATGTTGCA CAGGGAGTrA CAGAATGTTC TCATGACTGA A'ITGC'rT=A AAT'ITCACAG TGTGCCTGCA TITGAAGTCT TGGAAATATC TCCCCAGGAA GTATCUTCAG GCAGACTAT1F GAAGTCGGCC TCATCCCCAC CACTGCATAC ATGGCTGACA GTIIGAAAA AAGAGCAGGA GTTCCTGGGG GTGAGTGAGC 20 CTCCTCCAAC ThJ'GACTAGA GTAAGGGT17G GGTCTAGAAA AGAATAflGA GflGCATCAA CTGTITTCCC ACTTGGATTC ATGAGAGGTG TTAGGTCCTT TAAAAAACAT GGTAGATAAA GAG'rrGACAC TAACTGGGTC CITrGGGAA GAGCCAGAAG CATTTCCTCA TAAAGACTI17 AAATTGCTAG GACGAGAATG GCCAACAGGA GTGAAGGATT CATAAC'I=TA TC'ITTACTTA GATGTAAAGA ACAATTACTG ATGTTCAACA TGACTACATA CATAAAGGCG CATGGAGAAA AGTATTGGCC TITCCATGCAT TAGGTAGTGC TTGTATCAAT TCTT1ATAGTG 25 GCTAGGGTAT CCTGGAAAAT CTTACGTGTG GATCAMICT CAGGACAGTC TAGGACACTA ACGCAGTC TCATGTITGG CrrCTATTAT TAAAAAATGA TACAATCTCG GGAAAATIT ThrGA=F~C ATGAAATTCA TGTGT C TATAGGTAAC ACAAATTCTG ACTGCTATGA TATGCC'ITTG 'TPTGGAACA GTTGTCTGCT CTGTACTTGA TATrCACAC ATTGAGGGAG ACA'rTrC ATCA'TT7AAA GCAGGTTATC CATTCTGGGG AGCCATA1TT GTGAGTATAT ATCTATAATT1 G'ITTCTGAAA TAACACTGAA CATAGGTIT TCTCTTTCTC 30 AGATGTAACC AGTrG'TTfAT TCCCAGTATT AAGATGATAT TFrATAATTCT TAATTATAAA TATATGTGAG CATATATAAC ATAGATATGC TCATTAACAA CAACAAAAGA rrC'TAC AATI'AACGGT GGGTTAAACA 'TAGCCCAC AGTITTATCC CATGAGAAAC CTGAATCTAA TACAAGTTAA ATGACTTGCC TAAGGGCCAC TTGACTAATA GTAATTGAAC CTAAACTC AGAATCCAAC TCCAGGAACA TACTTCTAGC ACTATTCATC AATAAAGT'FA TATGATAAAT ACATACAACT TTATCTGTCA ACTAAAAATA ACAACAGAGG CTGGGCATGG 35 TGGCTCACAC CCGTAATCCC AGCACTrTGG GAGGCTGAGG CAGGTGGATC ACCTGAGGTC AGGAGTrTGA GACCAGCCTG ACCAACATGG TGAAACCTCA TCTCTACTAA ATATAAAAAA TrAGCTGAGT GTGATAGTGC ATACCTGTAA TCCAGCTACT TAAGAGGCTG AGGCAGGAGG CITG M~GAA CCTGGAAGGC AGAGGTTGCA GTGAGCTGAG ATTGTGCCAT TGCACTCCAG CCTGGGCAAT AAGTGCGAAC TCTGTCTCAA AATAATAATA ATAATAATAG AAAATAAAGT TGTCTTCATG AAAAATGAGG AAAGAGATTG CTGGGGTGAG AAACATTAAG 40 ATCAATGGGC ATATGGTGAC CTTCTATGCC CTAGAAACTC TITTANGGTA TITTCTCCTG GTATCTCT-I7 TACNCATCGT TCTATCTGGA AAAATAGGTG GATGAGTGAG ATAATAACGG TATATACT'IT YTAAAGGTCT AATTGACATA TATAAATTGC AAGTATrCA GATGTCAATT TGCTAACCTT GACACACATA GACACACATG AAAACATCAC CACATTAATA CAATGTATGT ATCCATCATT CCAAAAGCT CCCTGTGTAT CTTrGTAACT C'ITTCTTCCT CCCTCCACTC CTTGTCCTCT CGTTCCCAAG AAAACATTGA TCTGCTTCCT GTGAATATAA 45 ATT1AACTTAC AYTI1AGA GC'ITrATATA AGTATG'rrCT CTT7ACTGT7 TGTCTTCCTT CGCTGCACAG TrA FTrTGAG ATrTTCAAG TTTTTrCIT ATATCGATAC TTCATTCACA AGAATATATT TTAATTCTAG ACTATGTCAC A'I17GACTFTG TCGTCTGCTA AATCCTTAGT GCTCAGATGA C117G I1CAGG ACTCTC=TG AACCTGTACC TCTGTTANAT TGAAACTTGT CTCTACTGTC 'TTrA'I=C AAACACAGCT TA I1AGGTGT CTCTCAACCC ATCAAACNCA CAATCTGAGT CT7AGGAGA TI1GCTTGAA LTTGTGCTAT TGACTTATAT 50 NTATATNAAA TNTGTAAATG 'I=GGTAAAA ATATCATCAT GTACNT'=C ATAATTACGC TATNTNCACA TGATATATGT CAGACTCTGG AAATATGCAT GCCACAGACA CGTGTTTCTr GCCTAAAGGG GCTGATGGAA GACNCACATA CNAATAGACG ATTGCAGTAG AATGAGAGTG GTGGTCTAAN CAGTACATGT CCTGATGTrG CTCGGACAGT TACTACNCCA AGAGTACCCC CTGCATrGTC AGGGTTAGCA TCTCCTGGAA GCCTCATGTA AATGAAGAAT TTCATGCTCC ATCCAGGACC TAATGAATAA GAATCTGCAT MTAGCAAGA CCCTCATATG 55 ATTCATATAC ACThI11"11 'TTTrA GATGGAGTCT CACTCTTGTC GCCCAGGCTG GAGTGCAATG GCATGATCTT GGCTCACTGC AACCTCTGCC TCCCGGGUfC AAGTGATI1CT CCTGTCTCAG CCTCCCTAGT WO 00/62736 PCT/US00/08020 45 AGCTGGGACT ACAGGTGCAT GCCACAGTGG CTGGCTAATT TT7GTATTTT TAGTAGAGAC AGGGTTTCAC CATTTTGGTC AGGCTGGTCT TGAACTCATG ACCTCCGGTG ATTCCCCCGC CTCGGCTTCC CAAAGTGCTG GGATTACAGA CATGAGCCAC CACACCCGCC TTATTCGTAT ACNCATTrAA TTCTGAGAAG CACTCTATAG AAAATAAGAA TAAGAAAATA TTGGGCTCAC AGGTGACATT AATAAGTAAC TTTATCGAGT ACCCCAAATT 5 TTACCTATGT TTGGAAGATG GGGTTAAAAG GACACATTGA AAACAAGAAC TCATTGTGGC TTTTTTTTCC TCCTTTTGA ACAGTTTTCT ATTTCTGGAA TGTTGTCAAT TATATCTGAA AGGAGAAATG CAACATATCT GGTGAGTTGC CCGTTTCTGT CTTTGTCCAT CCTTGAAAAG ATAAGAAGAA CAGAGTTA AGAGTCTTAA GGGAAACACA TCTGTCTC CTATATTACT TGTGAATGTG GATATATGAT TTGTTTCAA TCTATTTTGT GTCCTAAGGC TTTTTGCAAC AGAAGTTGGA TATATCATTA GAAACATAAA TTGTACCATT TAACATACAT 10 GAAGTTATG TTTACCTTGA CGTTCTTCTA AAAAGTGTCC TACACCGGCA TTGTCC17GT AGGCATATTC ACATGATCAA ATAAAATAAT TAGTTCAA TTAAGGAGAA TATTTGAGGA AAGACCGTAC GTGTTCATGT GGTTCCTGAA GGCAGTCCAG TGAGAAAGTA ATATATGCTT CATTAAACAA TGCGGACATT TTCAGGGTTT CCCTTTTAA CCAAAATTTG GAAGCAATGT GGAATTTACT GGATGCATCC AGCCCTGAAA TGAAGATAGG TTTATTGAAT GTGCCAGCAA GTGCAGGCCC AGGTCTGAGT GTTCTTCATT ATTIATCAGGT GAGAGGAAGC 15 CTGGGAGCAA ACACTGCCAG CAGCATAGCT GGGGGAACGG GAATT1ACCAT CCTGATCATC AACCTGAAGA AGAGCTTGGC CTATATCCAC ATCCACAGTT GCCAGAAATT TTTGAGACC AAGTGCTTTA TGGCTTCCTT TTCCACTGTA TGTATTTTTT TTTGTGTGGG AAGACTAAGA TTCTGGGTCC TAATGTAAGT AAGAAGCCCT CTTCTCCTGT TCCATGAACA CCATCCTTTT CTGTAACTTC TATT1ACACAG TATAGTGGTT CTGTAAGTTC ACACAGCCCA GGGAGATGCT GGCTGCCCAC TCCCCTCAAC CCAGGCAAAT TCCTCGGGGT TAAAGTTATC 20 TACTGCAAGT GACGATCTCT GGGTTCT GTGCCTGTGT TTGTGTGTGT GTGTGTGTGT GTGTGTGTGT GTATGTGTCA CTTTAAAAGG ACTGGTCAGA TGGTAGGGAG ATGAAAACAG GAGATGCTAT AAGAAAATAA ACTTTTGGGG CGAATACCAA TGTGACTCTT TTTGTTTGTC ATTTGTTGCT GTTCAATAGG AAATTGTAGT GATGATGCTG TTTCTCACCA TTCTGGGACT TGGTAGTGCT GTGTCACTCA CAATCTGTGG AGCTGGGGAA GAACTCAAAG GAAACAAGGT AGATAGAAGC CCGATATAAA ATCTTGAATG ACAGGTTAAC GAATTGGAGC 25 TTTATrCCTT AAAATATGGC CTGGGTTC TGAAACATTT CTTCCAGAAA ATAGTTTCTC CAAGTTTTAT TACTTTGGTT TACAAATCTC ACATAAAT CACATTAT ACCATAAGTA GCACACATTT CATAATATTC CTCTGAATGA GGGTTGGGAT AATAGGACTG ATATGTTAGA AATGCCTTAA AGTGTGTGGA GCATGAGAGA TGGATGTACA GAAGGCTTGT GAGGAAACCA CCCAGGTATC TGGCCTTGTT TTCTGCCCCA GAACTAGCCG CCTATTCCTG TTTCTGTTTT ATTCCTTTGT TTCTTGACTT TTCCTTCCA ACTTGCTCTA AAACCTCAGT 30 TTTCTTTCCT TTCTGATTCA TGACTACCAA ATGTTCAC TTGCCTCACC CGTCCATTAC ACCTTTGATA AGAACCACCA GACCTTGTGC TCATGTACTT GCCCATGTCT GATGGAAGAA ACATACTCTC TCCATCTGTC CACTTTCCTG AGGCATTCAA GTCTAGCCAC CTTTTAAAAT CACTCTCCTC CAGGCTGGGC ACGGTGTCAC GCCTGTAATC TCAGCACTTT GTGAGGCTGA GGAGGGCGGA TCACTTGAAG TCAGGAGTTC AAAACCAGCC TGGCCAAATG GCAAAACCAA ATCTTCTTCA ATTATAACCA AATCTTAAAC CAAATCTCTA CTAAAAAATA 35 CAACAAAACA AAACAACAAC AACAAAAACA GAAAAGGAAA CATTAGCCCA GCGTGGTGGC AGGTACCTGA GGTTCCAGAT ACTTGGGAGG CTGAAGCAGG AGAATCGCT-T GAGCCCAAGA GATGGAGGTT GCAGTGAGCC GAGATCATGC CACTGCACCA CAGCCAGGGT GACAGAGCCA TACTTCCCAG CACATTGGGA GGCCAAAGCT GAAGAATAAT TTGAGGTGAG GATTTGGAGA CCAGCCTGGC CAACATGGTG AAACTCCGTC TGTACTAAAA ATATAAAACT TAGTGGGGCA TGGGGGCACA CACCTGTAAT TTCAGCTACT TAGGAGGCTG AGGCAGGAGA 40 ATTGCTTGAA CCCGGGAGGC GGAAGTTGCA GTGAGCCAAG ATCGTGGCCA CTGCACTCCA GCCTGGGTGA CATAGTGAGA TTCTGTCTCA AAAAAAATAA AAGAAATTTA AAAAATCACT CTCTTCCAAA GATAGATAAA TAAGACAGCA GATATACTAA GGAATAACCT CACCAACTTG TCATTGACTG ACATGATTTC TTTTGGCCCA CTTGGCCAGC TAGTCTGGTT TGGTTTCTG GAAATGAAAG AAATAATCAG AGTTTAATGA CAGAGAGCGT GAGACCCAGA AAGACAAAAG TAGATGAGGT AAGTCTCTTG AGCGAGACTT CTAGGGATGG GAAATTTGTG 45 GTGATTGATA TGAAATGATT TTTCCCTTAT CAGGTTCCAG AGGATCGTGT TTATGAAGAA TTAAACATAT ATTCAGCTAC TTACAGTGAG TTGGAAGACC CAGGGGAAAT GTCTCCTCCC ATTGATTTAT AAGAATCACG TGTCCAGAAC ACTCTGATTC ACAGCCAAGG ATCCAGAAGG CCAAGGTTTT GTTAAGGGGC TACTGGAAAA ATTTCTATTC TCTCCACAGC CTGCTGGTTT TACATTAGAT TTATTCGCCT GATAAGAATA TTTTGTTTCT GCTGCTTCTG TCCACCTTAA TATGCTCCTT CTATGTAG ATATGATAGA CTCCTATTTT TCTTGTTTTA 50 TATTATGACC ACACACATCT CTGCTGGAAA GTCAACATGT AGTAAGCAAG ATTTAACTGT TTGATTATAA CTGTGCAAAT ACAGAAAAAA AGAAGGCTGG CTGAAAGTTG AGTTAAACTT TGACAGTTTG ATAATATTTG GTTCTTAGGG TTTTTTTTTT TTTTAGCATT CTTAATAGTT ACAGTTGGGC ATGATTTGTA CCATCCACCC ATACCCACAC AGTCACAGTC ACACACACAT ATGTATTACT TACACTATAT ATAACTTCCT ATGCAAATAT TTTACCACCA GTCAATAATA CATTTGCC AAGACATGAA GTTTTATAAA GATCTGTATA ATTGCCTGAA 55 TCACCAGCAC ATTCACTGAC ATGATATTAT TTGCAGATrG ACAAGTAGGA AGTGGGGAAC TTTTATTAAG TTACTCGTTG TCTGGGGAGG TAAATAGGTT AAAAACAGGG AAATTATAAG TGCAGAGATT AACATTTCAC WO 00/62736 PCT/USOO/08020 46 AAATGTTTAG TGAAACATTT GTGAAAAAAG AAGACTAAAT TAAGACCTGA GCTGAAATAA AGTGACGTGG AAATGGAAAT AATGGTTATA TCTAAAACAT GTAGAAAAAG AGTAACTGGT AGATTGTT AACAAATTAA AGAATAAAGT TAGACAAGCA ACTGGTTGAC TAATACATTA AGCGTTTGAG TCTAAGATGA AAGGAGAACA CTGGTTATGT TGATAGAATG ATAAAAAGGG TCGGGCGCGG AGGCTCACGC CTGTAATCCC AGCCCTTTGG 5 GAGGCCGAGG TGGGCAGATC ACGAAGTCAG TAGTTTGAGA CCAGCCTGGC CAACATAGTG AAACCCCGTC TCTACTAAAA ATACAAAAAA AAAATTAGCT GGGTGTGGTG GCAGTCACCT GTAGTCCCAG CTACTTGGGA GGATGAGGCA GGAGAATCGC TTGAACCTGG GAGGCGGAGG TTGCAGTGAG CCGAGATCGC ACCAGTGCAC TCCAGCCTTG GTGACAATGG GAGACTCCAT CTCAAAAAAA AAAAAAAAAA AAAAAAGATA AAAAGTCAGA AATCTGAAAA GTGGAGGAAG AGTACAAATA GACCTAAATT AAGTCTCATT TTTTGGCTTT GATTGGGG 10 AGACAAAGGG AAATGCAGCC ATAGAGGGCC TGATGACATC CAATACATGA GTTCTGGTAA AGATAAAATT TGATACACGG TTTGGTGTCA TTATAAGAGA AATCATTATT AAATGAAGCA AGTTAACACT CTAAGAGAAT TATTGAGA TAGAAGTGAA GCTAAGCTAA ACTTCACATG CCTATAATTG GAGGGAAAAA CTAAGGATAA AATCTAGCCT AGAAGATACA ATAATTAGTC ATAAACATGC ATTGTGAAAC TGTAGAGAGC AGGTAGCCCA AAATAGAGAA AGATTAGATA AAGAGAAAAT AAGTATCCAT CAGAGACAGT ATCTCTAGGC TTGGGCAAGA 15 GAAAAGTCCA CAGTGATAAG CAACTCCACC TAAGGCATGA ATATGCGGCA GAGAAAACAG CAATAGTGAA TGAATGCAAA AGGTGCTGAG CAAATTCCAC ACATGAGTAT TGTGCATGAG TAAATGAATA AAACATGC AAAGACCTTT AGAGAAAGAG AATGGGAGCA TATGTGCGAA ATAAGATAGT TGATTATGAA TAGAAGGTAG TGAAGAAAAG CAAGCTAAGA AAAAATTCTG TTTATAAAAG AAGGAAAAGA TAGTTTATGT TrTTAGCCTA AGTATAAGAG TCCTACAGAT GGACTGAAAA AAATCAGTCT GAGAGTATTA GTCACAATTA ATGAAATAAT 20 TACATTTTAT GTATTGAGGA TGCCAAGATT AAAAGGTGAC AGGTAGATGT TAATTTCCCT AGATTGTGAA AGTGATCACG ACAATCACAC AACAAATAAT TAAGTGACTT GGTATGCTTT ATTTAATTGT AGGGCCTGAG GTTTTCCATT CTCATTTC TAAAATACAA TTTTGTTTCT CCAAATTTGA CAGCAGAATA AAAACCCTAC CCTTTCACTG TGTATCATGC TAAGCTGCAT CTCTACTCTT GATCATCTGT AGGTATTAAT CACATCACTT CCATGGCATG GATGTTCACA TACAGACTCT TAACCCTGGT TTACCAGGAC CTCTAGGAGT GGATCCAATC 25 TATATCTA CAGTTGTATA GTATATGATA TCTCTTTAT TTCACTCAAT TTATATTTTC ATCATTGACT ACATATT7CT TATACACAAC ACACAATTTA TGAATTTTTT CTCAAGATCA TTCTGAGAGT TGCCCCACCC TACCTGCCTT TTATAGTACG CCCACCTCAG GCAGACACAG AGCACAATGC TGGGGTTCTC TTCACACTAT CACTGCCCCA AATTGTCTTT CTAAATTTCA ACTTCAATGT CATCTrCTCC ATGAAGACCA CTGAATGAAC ACCTTTTCAT CCAGCCTTAA TTTCTTGCTC CATAACTACT CTATCCCACG ATGCAGTATT GTATCATTAA 30 TTATTAGTGT GCTTGTGACC TCCTTATGTA TTCTCAATTA CCTGTATTTG TGCAATAAAT TGGAATAATG TAACTTGATT TCTTATCTGT GTTTGTGTTG GCATGCAAGA TTrAGGTACT TATCAAGATA ATGGGGAATT AAGGCATCAA TAAAATGATG CCAAAGACCA AGAGCAGTTT CTGAAGTCCT CCTTTTCATC AGCTCTTTAT CAAACAGAAC ACTCTATAAA CAACCCATAG CCAGAAAACA GGATGTAGGA ACAATCACCA GCACACTCTA TAAACAACCC ATAGCCAGAA AACAGAATGT AAGGACAATC ACCAGCCATC TTGTCAAT AATTGATGGA 35 ATAGAGTTGA AAGGAACTGG AGCATGAGTC ATATTGACC AGTCAGTCCT CACTCTTATT TACTTGCTAT GTAAACTTGA GAAAGCTTTT TTCTCTTTGT GAACCTCAGG TTACATCT GAAAATGAGA AATTTGGAAC AAAAGATTCC TAACTGGTCT TTCTGTTCCC ATATTCTGTG ATTTTTCAAT ATTTAGGATT TTTGGTAATC ACAATTACTT AGTTTGTGGT TGAGATAGCA ACACGAATCA GAACTATTTG GTGGACATAT TTTCAAAGGA GTAGCTCTCC ACTTTGGGTA AAGAAGTGAT GCNGGTCGTG GTGGCTCACG CCTGTAATCC CAGCACTTTA 40 GGGAGGCCAA GGCGGGTGGA TCACGAGGTC AGGAGATCGA GACCATCCTG GCTAACACGG TGAAACCCCG TCTCTACTAA AAAATACAAA AAATTAGCCA GGCGTGGTGG CGGGCGCCTG TAGTCCCACG TACTCGGGAG GCTGAGGCAG GAGAATGGCA TGAACCAGGG AGGCGGAGCT TGCCGTGAGC CGAGATAGCG CCACTGCAGT CCCTCCTGGG CAAAAGAGCA AGACTGCGTC TCAAAAAAAA AAAAAAAAAA AAAAAAAGAA GTGTGTGGAG TAGCAGGACA CCTGCAACAA TAATATTTTT CTAAATCCCT CTGAAAAATG CTAATCAAAG GGTTTTC 45 CTAAAAATTG TCTTAGAAAT AAAATTTCCC CTGGGAGA CCGAGGCTGG CAGATCACGA GGTCAGGAGA TAGAGACCAC GGTGAAACCC CGTCTCTACT AAAAATACTA AAAATTAGCC GGGGNGTGGT GGTGGGTACA CCTGTAGTCC CAGCTACTTG GAGGCTGAGG CTGGAGAATC ACGTGAAC GCCACGTGCT GCTGGGTCTC AGTCCTCCAC TTCCCGTGTC CTCTGGAAGT TGTCAGGAGC AATGTTGCGC TTGTACGTGT TGGTAATGGG AGTTTCTGCC TTCACCCTTC AGCCTGCGGC ACACACAGGG GCTGCCAGAA GCTGCCGGTT TCGTGGGAGG 50 CATTACAAGC GGGAGTTCAG GCTGGAAGGG GAGCCTGTAG CCCTGAGGTG CCCCCAGGTG CCCTACTGGT TGTGGGCCTC TGTCAGCCCC CGCATCAACC TGACATGGCA TAAAAATGAC TCTGCTAGGA CGGTCCCAGG AGAAGAAGAG ACACGGATGT GGGCCCAGGA CGGTGCTCTG TGGCTTCTGC CAGCCTTGCA GGAGGACTCT GGCACCTACG TCTGCACTAC TAGAAATGCT TCTTACTGTG ACAAAATGTC CATTGAGCTC AGAGTTTTG AGAATACAGA TGCTTTCCTG CCGTTCATCT CATACCCGCA AATTAACC TTGTCAACCT CTGGGGTATT 55 AGTATGCCCT GACCTGAGTG AATTCACCCG TGACAAAACT GACGTGAAGA TTCAATGGTA CAAGGAT7CT CTTCITTGG ATAAAGACAA TGAGAAATTT CTAAGTGTGA GGGGGACCAC TCACTTACTC GTACACGATG WO 00/62736 PCT/USOO/08020 47 TGGCCCTGGA AGATGCTGGC TATTACCGCT GTGTCCTGAC ATTTGCCCAT GAAGGCCAGC AATACAACAT CACTAGGAGT ATTGAGCTAC GCATCAAGAA AAAAAAAGAA GAGACCATTC CTGTGATCAT TTCCCCCCTC AAGACCATAT CAGCTTCTCT GGGGTCAAGA CTGACAATCC CGTGTAAGGT GTTCTGGGA ACCGGCACAC CCTTAACCAC CATGCTGTGG TGGACGGCCA ATGACACCCA CATAGAGAGC GCCTACCCGG GAGGCCGCGT 5 GACCGAGGGG CCACGCCAGG AATATTCAGA AAATAATGAG AACTACATTG AAGTGCCATT GATTTTGAT CCTGTCACAA GAGAGGATTT GCACATGGAT TTTAAATGTG TTGTCCATA-A TACCCTGAGT TTTCAGACAC TACGCACCAC AGTCAAGGAA GCCTCCTCCA CGTTCTCCTG GGGCATTGTG CTGGCCCCAC TTTCACTGGC CTTCTTGGTT TTGGGGGGAA TATGGATGCA CAGACGGTGC AAACACAGAA CTGGAAAAGC AGATGGTCTG ACTGTGCTAT GGCCTCATCA TCAAGACTTT CAATCCTATC CCAAGTGAAA TAAATGGAAT GAAATAATTC 10 AAACACAAAA AAAAAAAAAA AAAAAAAA GCCGGAGCCG ACTCGGAGCG CGCGGCGCGG CCGGGAGGAG CCGAGCGCGC CGGGCGCGGC GTGGGGGCGC CGGCTGCCCC GCGCGCCCAG GGAGCGGCAG GAATGTGACA ATCGCGCGCC CGCACCGTAG CACTCCTCGC TCGGCTCCTA GGGCTCTCGC CCTCTGAGCT GAGCCGGGTT CCGCCCGGGC TGGGATCCCA TCACCCTCCA CGGCCGTCCG TCCAGGTAGA CGCACCCTCT GAAGATGGTG ACTCCCTCCT GAGAAGCTGG ACCCCTTGGT AAAAGACAAG GCCTTCTCCA AGAAGAATAT GAAAGTGTTA 15 CTCAGACTTA TTTGTTTCAT AGCTCTACTG ATTrCTrCTC TGGAGGCTGA TAAATGCAAG GAACGTGAAG AAAAAATAAT TTTAGTGTCA TCTGCAAATG AAATTGATGT TCGTCCCTGT CCTCTTAACC CAAATGAACA CAAAGGCACT ATAACTTGGT ATAAAGATGA CAGCAAGACA CCTGTATCTA CAGAACAAGC CTCCAGGATT CATCAACACA AAGAGAAACT TTGGTTTGTT CCTGCTAAGG TGGAGGATTC AGGACATTAC TATTGCGTGG TAAGAAATTC ATCTTACTGC CTCAGAATTA AAATAAGTGC AAAATTTGTG GAGAATGAGC CTAACTTATG 20 TTATAATGCA CAAGCCATAT TTAAGCAGAA ACTACCCGTT GCAGGAGACG GAGGACTTGT GTGCCCTTAT ATGGAGTT TTAAAAATGA AAATAATGAG TTACCTAAAT TACAGTGGTA TAAGGATTGC AAACCTCTAC TTCTTGACAA TATACACTTT AGTGGAGTCA AAGATAGGCT CATCGTGATG AATGTGGCTG AAAAGCATAG AGGGAACTAT ACTTGTCATG CATCCTACAC ATACTTGGGC AAGCAATATC CTATTACCCG GGTAATAGAA TTTrATTACTC TAGAGGAAAA CAAACCCACA AGGCCTGTGA 'TTGTGAGCCC AGCTAATGAG ACAATGGAAG 25 TAGACTTGGG ATCCCAGATA CAATTGATCT GTAATGTCAC CGGCCAGTTG AGTGACATTG CTTACTGGAA GTGGAATGGG TCAGTAATTG ATGAAGATGA CCCAGTGCTA GGGGAAGACT ATTACAGTGT GGAAAATCCT GCAAACAAAA GAAGGAGTAC CCTCATCACA GTGCTTAATA TATCGGAAAT TGAAAGTAGA TTTTATAAAC ATCCATTTAC CTGTTTGCC AAGAATACAC ATGGTATAGA TGCAGCATAT ATCCAGTTAA TATATCCAGT CACTAATTTC CAGAAGCACA TGATTGGTAT ATGTGTCACG TTGACAGTCA TAATTGTGTG TTCTGTTTrC 30 ATCTATAAAA TCTTCAAGAT TGACATTGTG CTTTGGTACA GGGATTCCTG CTATGATTTT CTCCCAATAA AAGCTTCAGA TGGAAAGACC TATGACGCAT ATATACTGTA TCCAAAGACT GTTGGGGAAG GGTCTACCTC TGACTGTGAT ATTTGTGT TTAAAGTCTr GCCTGAGGTC TTGGAAAAAC AGTGTGGATA TAAGCTGTTC ATTTATGGAA GGGATGACTA CGT7GGGGAA GACATTGTTG AGGTCATTAA TGAAAACGTA AAGAAAAGCA GAAGACTGAT TATCATTTTA GTCAGAGAAA CATCAGGCTr CAGCTGGCTG GGTGGTTCAT CTGAAGAGCA 35 AATAGCCATG TATAATGCTC TTGTTCAGGA TGGAATTAAA GTTGTCCTGC TTGAGCTGGA GAAAATCCAA GACTATGAGA AAATGCCAGA ATCGATTAAA TTCATTAAGC AGAAACATGG GGCTATCCGC TGGTCAGGGG ACTTTACACA GGGACCACAG TCTGCAAAGA CAAGGTTCTG GAAGAATGTC AGGTACCACA TGCCAGTCCA GCGACGGTCA CCTTCATCTA AACACCAGTT ACTGTCACCA GCCACTAAGG AGAAACTGCA AAGAGAGGCT CACGTGCCTC TCGGGTAGCA TGGAGAAGTT GCCAAGAGTT CTTAGGTGC CTCCTGTCTT ATGGCGTTGC 40 AGGCCAGGTT ATGCCTCATG CTGACTTGCA GAGTTCATGG AATGTAACTA TATCATCCTT TATCCCTGAG GTCACCAGGA ATCAGG-3'(SEQ.ID NO:3002) Human Enzyme-related Antisense Polynucleotide 5'-CTT GCT CCT GGG GGC CTC CTG GTC CCT CTG GCT G TT CCC GGC CCT GGB CTG GGG CBG GGG CCG CGT BGG CGC GGC TCG CCB GGB CGG GCB GCG CCB GCB GCB GCB GGC TCB GCB TCC TGG CCB CGG BBT 45 TCC GGT GTG CGG GGC CTG GTG CC CCT GGG CCT CGG GTG CTG CCT GT GCG CTG CCT TCT TCT CCT GG GTC CTC GCC GGG GCC CTT GCT GCC CTG GCT GT GCC CTG GGG GTC TGG GTT CGG CTG T CCC CBG CBG GBC CBG TCC CBT CCB CBG CGT GTG BTG BGT BGC CBT TCT CCT GCB GCC GBG GGG CGC GGG CGB GCB TCG C TTT GGG CTT TTC TCC TTT GGT T TGB GCG CCB GGB CCG CGC BCB GCB GCB GGG CGC GGG CGB GCB TCG CBO COG CGG GCB GGG GGGCTCCCGC CGCGBGBGGT TBTGGGCTCC CBGGBCCBCC 50 CGCBCCGCGC GGBCGTTTBC BTTCGCCBCG CBGTGCGCGG CCGBCBTGBC GBBGTTGGGC GCBBTCBGGG TGGCGCCGCB GBBGTGGCCT CCGCGCBGCT GCBGGGBCBC CBTGBBGGGC CBCGCGTGGG GCCGCGCTCG CCGGCCCCCC BCBBTCTCCG BGGCCBGCGC GGTGCCCCCC BGCBGCBBGG CCGGCBGGBC BCBGGCGBGG BGBCBCGCGB GTCGGCGGCC GBGGGTCBTG GTGGGGCTGG GGCTCCGGGG TCTCTGCCCC TCCGTGCTGG TGGGGCTGGG GCTCCGGGG TCTCTGCCCC TCCGTGCCGC GTGGGGCCGC GCTCGCCGGC CCCCCCCTGC 55 CGGGTGGGCT CCCGCCGCGC GCCGGCCTGC CGGCCCCTCG TGGGTCCTGC TGGCCGGGTC CGGGTCCCGG GGGTGGGGCG CGBGTCGGCG GCCGBGGGTC CCCTCCBCBT CTGCTCTGBC CTGCTGGBCT CTGGBTCTGB BGBTBCGCCB TGTBGGGGCG GGBGTGGGGC CTGCTCTCCC GGCCTCCGBT GBTCTCCCCT GCCTCBGCCC CBGTGGGTBG GBGBBBGGCC BGCBGBBGCB GGBGTGGCTG CBTCTTTCCT GGTGGGGCCT GCTCTCCCGG WO 00/62736 PCT/USOO/08020 48 CCTCCGTGTG TTGCTGGGTG TTTTCCCGTC TCTGGTCTGC CTTCGGGGGT CGT CCGGGGCTGC BGCBBCCTCB TCBGCTCTTG CCTGGBGTGG CTCBGCCTGG GCCTGCBGGG CCBCCBGGBG BBTGGCBGCB BGGBTGGCGB GGGTCCTCBT GGCTGGGGTC BCBGBTCCTC TBGCTBGGCB GGGTGBCCBG BGBGGGC GGG TCC TCB TGG CTG GGG GCC TGG GCC TGC BGG GCC GCT CTT GCC TGG BGT GGC TC GCC CBG BGT CTT CCC TGG T 5 CGCTGCBBTC TGCTCCGGGG CTGCBGCBBC CTCBTCBGCTC TTGCCTGGBGTG GCTCBGCCTGG GCCTGCBGGG CCBCCBGGBGB BTGGCBGCBBG GBTGGCGBGGG TCCTCBTGGC TGGGGTCBCCT GGBGGBGGGB GBGCBGGGGG TCCTCBTGGC TGGGGTCCCT CTCTCCCGTC CT CGG TTT1 CCT TTG CGG TC TTG GCC CGG GCT CCG GGT G CCC GCC CGC CCG CCG GCC GCC GC CCC GCC GGG CTG TCC CCG CCC CGC CCC GGC CCG GGG CGC GGG GG CGG CCC TCC CGC CCC TCT GG GCC GGC GCG GGC GTC GG CCG CTC GCG CCT 10 GGG GTT CCC TCT CCT CCC CCT GTG C GCC TGC CTC TTG CTC TTCTGC GTC CGC TGC CTT CTC CC CTC TCC TCG GCC GTT GCC TGT GC TGT CCG TCC TGT CGC CCT TCC GTG GTG C TGT TGT CTC TTC TGC CCT C GGT GTG CTG GTG CTG GTG GTG GTG CCT CTG CCC GTG CTC GCCCTG CCT GGG CTG GCC TCT TCGGGT GTG GCT TTG GGG CTC TCT TGG TTG CCC TTT CT7 CTC GTG GTG CCT CTC CTC CCT GGC TTG GTC GT TGT CTG GGG TGG TGC TCC TCT CCC TTT CCC TGC TGG CCG TTT GT CCT GTT TTC TGT CTT CCT CT TTC 15 CTC CTG TTT CTC CGT TTG GCT TGC TGC TTG CGG GGC TGT CTC C CTT GCC CCT GTG GGC TTT CCC TGG TCC GGT CTT CTC CTT GGG GGT C GCC CTT CTT GGT GGG CTGGCT CGT CTG TCT TTT TCC TTC C TGG GGG TGG CCG TTG TGG GCG GTG TGG TCC GCC T TGC CTC TGC TGG TCT TTC CTCGGTBGBC GCGCTCGBBC TCGGGTGGGC CGGTGGTGBG CGGCGGCGBCB CGCGGBBGGC CCTGCGCGCC GBGBTCBCCTG CBGGGBGBBG TBGGCTTGCB GCBGGBCTCC CBGGBGGGTG BCBGCBGCCB GTBGBGCTBC CTCGTCCTT1C 20 BTGGTBCCGT CGGTGTGGTG GCBCGGGCTG TGTGTGBBGG CGBGCTGGGC CCCGTCTGCT GCTCCTCGTG CCGCCTCGTC CTTCA TGG TA CCGTCGGTGT GGTGGCCTCG GGTGGGCCGG TGGTGGGGCG CGCGCGCTCG CGTGGCTCCG GCTCTTCTTT CCCGGCTCCGT CGGCCCGGGG GCCTTGGTCT CCCTCGTCCT TCBTGGTBCC G BCCGGCGGBG CCGCCBGGGT GGBCTGGGBG TGGGTTTCTC CCCGCCGTTC TCBCCCBCCG CGCTGBGCTC BGCGCCTBBG BCTGCTGTTT CTGGBGCTCC TTGGCBBGCC BCBBBCBGCB GBGBGBBBBT CBTGBGCBBB 25 TBBTCCBTTC TGBBBBBBBG GGBTCBBBBB CCTCCCGTTC CCCGTTCGCC TGGCGCGCGC TGCGGGTTCC TCGTGGGTTT CTCCCCGCCG TTCTCCGGTC TGTTGCCTTT GTGGGCTTCT TGTCTTTTTG GCTGTTCTTT TCCTGCTTGG CGTCTTTTCC TT7CTTTGTG CTCGGTTGTG GGTCCGCTGG TCCTTTGCCC TGTGTGTTTC TGCTGCCCGT TCGCCTGGCG CGCGCTGCGG GTTCCTCGTG GGTTTCTCCC CGCCGTTCTC CGGTCTGTTG CCTTTGTGGG CT7CTTGTCT TTGGCTGT TCTTTTCCTG CTTGGCGTCT TTTCCTT7CT TTGTGCTCGG 30 T7GTGGGTCC GCTGGTCCTT TGCCCTGTGT GTTTCTGCTG GGBGCTGBTB CTGCBGATTT CBGBGGGBBG BBCCCTGBTB CTCBCCBGCT TCBGCTCTGG BGCBCBBGBG BBBGBGCBGC BGGGGGBGBG GBBGBBGCBG CBTCTTCCCB GBGBGGCTGC CTGBGCBBBT GCTGGTTTTC CTTTCCBGTC T'TGGGTTTTB TBBCTCCCBG BBGGCBBGBG BGGGGCBBGG CGTTTTCTTC TCTCGCTGGT TTTCCTTTCC TGGCAGTGGG TGGGGGTGGG GGTGGGGTGG CTTCCTTGTT CCTGGGGGTG TCCTCTTGCT CTGGGCTTTT CTCCCCTTTT CCTTCCTGTC 35 TGTTTTCCTG GGGCTCTCCT CTGTCTCTGT GTCCTTGCCC TGGCCCTCTT CCCTCTCCTG TCTCCTGTCC CTGTGT7CCG CCCGTCTTCC CTCTCCTGAC CTCCTTTTCC TCCGCTGGGT GGGGCCCTGC CTGTTCTCTG CTCCCTGGCT TGGGGTTTCT TCTGTGTGTC TTCTTCCTCT GTTGGCTGGC TTCTCCTTC TTTTGTCTTC CTGGGTGCCC C TTCTTCCTT TCTTGGGTCC TTGGTGCTTG GGCTGGG GCGTCT7GGG GTGCBGGGCC CBTCCTGCTG CGCCTGGGCG CTGCTGTGCG TCCGTCTGCT GGGGGGCCGG GGTGGCTGGG CCCTGCTTGC 40 CGCACGACCC CGGGCCGACC CGAGGCTCGG GGGGCTGTGT TCTGGCGCTG GTGGGCTTGG GCCCCTCTGG GGGCTGGGTT TCCTGCTGCG CCTGGGCGCT GGCGTCTTGG GGTGCGGGGC COOGGGCCG GGGGGCCGCT GTTCGTGGGC CTGGGGGTGC CTGTGGCTGC CGGTTGCCCC GGTTGGTGGC GCCGTCCTGC TGCCGGTCGT TGGCTGGGTC CCCCCGCCCG TTTCCTGGGG TCCGCGTGGG GTGCTCCGGT TCCTCGTGCC GCTGCTGCCT TGTCTTTCCG GCCGTGGCGG CGTGGTGGTC CGCCCCCCCT GGCCTTCTGC TCGGGGTCTG GCTGGTTGCC 45 GGTGCCCTTG GCGGCGGTCT TCTTCCTGGT GGCTCTGGGC CCGGCCGGTC TCGGGCGTCT CGTGTTCGCT CTTGTGCTGT TCCGGCCGCT CCTTCCTCTT CCGCCGCCGC CGCTCCCCGC CCGCTCGTCG CCCTGGCCCG GCCTCCTCCT GGCCGCTGTC TCGGGCOOCG GCCTTGGCGC TCCGTTTGGG GCTGCCTCTG GCGCTTCCGG CCCTCGGCCT GGGCGCTCTC TTCCGCCTGT .GCTGGTGGCC CTCGTGGGCC CCTCCTGGCC TCCGGTGTCC TGTGGTCCCC CGGCTGGTGG CCGGGCCGGT TGGGCGGGCG TGGGCGCCGG CGGGTCCTCC GGGCTGCCCT 50 TCTCCGCCGG GGGTCCCGCG CTCCTGCTGT TCCCTGGGCT C17CTGCCTC TCTCCTGGGT GGGTGCTGGG TGCCGGGGTC TCCGGGCTTG GCCCGCGCTG CTGGGCGTTC TGCGGTCTTG GGGTTGTCTG TGGCCCCGCT CGTGTCGCCC TCCGTCGCCC GTCGCCGGCC TCGTCCCCTC CTGGGTGCGC GGCGGGCTGG TCCTGGCGTT TTGCTCCTTC CTGGGCGTCT TGGGGTGCBG GGCCCBTCCT GCTGCGCCTG GGCGCTGCTG TGCGTCCGTC TGCTGGGGGG CCOGGGTGGC TGGGCCCTGC TTGCCGCACG ACCCCGGGCC GACCCGAGGC TCGGGGGGCT 55 GTGTTCTGGC GCTGGTGGGC TTGGGCCCCT CTGGGGGCTG GGTTTCCTGC TGCGCCTGGG CGCTGGCGTC TTGGGGTGCG GGGCCGGGGG GCCGGGGGGC CGCTGTTCGT GGGCCTGGGG GTGCCTGTGG CTGCCGGTTG CCCCGGTTGG TGGCGCCGTC CTGCTGCCGG TCGTTGGCTG GGTCCCCCCG CCCGTTTCCT GGGGTCCGCG TGGGGTGCTC CGGTTCCTCG TGCCGCTGCT GCCTTGTCTT TCCGGCCGTG GCGGCGTGGT GGTCCGCCCC CCCTGGCCTT CTGCTCGGGG TCTGGCTGGT TGCCGGTGCC CTTGGCGGCG GTCTTCTTCC TGGTGGCTCT 60 GGGCCCGGCC GGTCTCGGGC GTCTCGTGTT CGCTCT7GTG CTGTTrCCGGC CGCTCCTTCC TCTTCCGCCG CCGCCGCTCC CCGCCCGCTC GTCGCCCTGG CCCGGCCTCC TCCTGGCCGC TGTCTCGGGC GGCGGCCTTG GCGCTCCGTT TGGGGCTGCC TCTGGCGCTT CCGGCCCTCG GCCTGGGCGC TCTCTTCCGC CTGTGCTGGT GGGCCCTCGTG GGCCCCTCCT GGCCTCCGGT GTCCTGTGGT CCCCCGGCTG GTGGCCGGGC CGGTTGGGCG GGCGTGGGCG CCGGCGGGTC CTCCGGGCTG CCCTTCTCCG CCGGGGGTCC CGCGCTCCTG CTGTTCCCTG 65 GGCTCTTCTG CCTCTCTCCT GGGTGGGTGC TGGGTGCCGG GGTCTCCGGG CTTGCCCCGC GCTGCTGGGC GT'TCTGCGGT CTTGGGGTTG TCTGTGGCCC CGCTCGTGTC GCCCTCCGTC GCCCGTCGCC GGCCTCGTCC WO 00/62736 PCT/US00/08020 49 CCTCCTGGGT GCGCGGCGGG CTGGTCCTGG CGTTGCTC CTTCCTGG CTGCCCCBGT TTTGBTCCT CBCBTGCCGT GGGGBGGBCB BTGGCTGCCT CCCCGGGGTT TCTGCTGCTT GCTGCTTCTT TCCCGTCTCC CTTCTTTCCC GTCTCCTTTT TGCCTCTTTG GGTTCCTGTT GTTTCTGGCC TGCTTGGTGG CGGCTTGTGC GTTTCCTCTC TCTTCTCTTG GGTCTCCGCT TCTCGTCCTG CCTITTCCTG TCTCTGTCGC GCCGTTCCTC 5 CTCCGGCGTC CTCCTGCCCT GTGCTGTTTG CCTCGGGTGG TGCGGGTCCC GGTGCTCCCC CGGCGGGCCG GCTGGTTGCC. TGGGCCTGTC TGGTGGGGTG TGGGGCCGCT GGGTTGGGGG TGTGGTGGGC TCTTCTGTGG CCTGTGGGGC TGTTGGTGTC TCTGTGGGCG TGTGCTGGGT CTTGGGGCTT CCTCCCTTGT GCTGGGTGCG GCCTCCCCGC CCCCCTTCTG GGCCGGTGGC CTGGCTCCTT GTGGGCGCTT CTGGCTCTTG CCCTGTCCTT CTTCGCCTCG TGGCTGCTGG GCTGC GCCGCCGCCG CCAAGATGGC GGACCTGGAG GCGGTGCTGG 10 CCGACGTGAG CTACCTGATG GCCATGGAGA AGAGCAAGGC CACGCCGGCC GCGCGCGCCA GCAAGAAGAT ACTGCTGCCC GAGCCCAGCA TCCGCAGTGT CATGCAGAAG TACCTGGAGG ACCGGGGCGA GGTGACCTTT GAGAAGATCT TTTCCCAGAA GCTGGGGTAC CTGCTCTTCC GAGACTTCTG CCTGAACCAC CTGGAGGAGG CCAGGCCCT7 GGTGGAATTC TATGAGGAGA TCAAGAAGTA CGAGAAGCTG GAGACGGAGG AGGAGCGTGT GGCCCGCAGC CGGGAGATCT TCGACTCATA CATCATGAAG GAGCTGCTGG CCTGCTCGCA TCCCTTCTCG 15 AAGAGTGCCA CTGAGCATGT CCAAGGCCAC CTGGGGAAGA AGCAGGTGCC TCCGGATCTC TTCCAGCCAT ACATCGAAGA GATTTGTCAA AACCTCCGAG GGGACGTGTT CCAGAAATTC ATTGAGAGCG ATAAGTTCAC ACGGTTTGC CAGTGGAAGA ATGTGGAGCT CAACATCCAC CTGACCATGA ATGACTTCAG CGTGCATCGC ATCATTGGGC GCGGGGGCTT TGGCGAGGTC TATGGGTGCC GGAAGGCTGA CACAGGCAAG ATGTACGCCA TGAAGTGCCT GGACAAAAAG CGCATCAAGA TGAAGCAGGG GGAGACCCTG GCCCTGAACG AGCGCATCAT 20 GCTCTCGCTC GTCAGCACTG GGGACTGCCC ATTCAT7GTC TGCATGTCAT ACGCGTTCCA CACGCCAGAC AAGCTCAGCT TCATCCTGGA CCTCATGAAC GGTGGGGACC TGCACTACCA CCTCTCCCAG CACGGGGTCT TCTCAGAGGC TGACATGCGC TTCTATGCGG CCGAGATCAT CCTGGGCCTG GAGCACATGC ACAACCGCTT CGTGGTCTAC CGGGACCTGA AGCCAGCCAA CATCCTTCTG GACGAGCATG GCCACGTGCG GATCTCGGAC CTGGGCCTGG CCTGTGACTT CTCCAAGAAG AAGCCCCATG CCAGCGTGGG CACCCACGGG TACATGGCTC 25 CGGAGGTCCT GCAGAAGGGC GTGGCCTACG ACAGCAGTGC CGACTGGTTC TCTCTGGGGT GCATGCTCTT CAAGTTGCTG CGGGGGCACA GCCCCTTCCG GCAGCACAAG ACCAAAGACA AGCATGAGAT CGACCGCATG ACGCTGACGA TGGCCGTGGA GCTGCCCGAC TCCTTCTCCC CTGAACTACG CTCCCTGCTG GAGGGGTTGC TGCAGAGGGA TGTCAACCGG AGATTGGGCT GCCTGGGCCG AGGGGCTCAG GAGGTGAAAG AGAGCCCCTT TTTCCGCTCC CTGGACTGGC AGATGGTCTT CTTGCAGAAG TACCCTCCCC CGCTGATCCC CCCACGAGGG 30 GAGGTGAACG CGGCCGACGC CTTCGACATT GGCTCCTTCG ATGAGGAGGA CACAAAAGGA ATCAAGTTAC TGGACAGTGA TCAGGAGCTC TACCGCAACT TCCCCCTCAC CATCTCGGAG CGGTGGCAGC AGGAGGTGGC AGAGACTGTC TTCGACACCA TCAACGCTGA GACAGACCGG CTGGAGGCTC GCAAGAAAGC CAAGAACAAG CAGCTGGGCC ATGAGGAAGA CTACGCCCTG GGCAAGGACT GCATCATGCA TGGCTACATG TCCAAGATGG GCAACCCCTT CCTGACCCAG TGGCAGCGGC GGTACTTCTA CCTGTTCCCC AACCGCCTCG AGTGGCGGGG 35 CGAGGGCGAG GCCCCGCAGA GCCTGCTGAC CATGGAGGAG ATCCAGTCGG TGGAGGAGAC GCAGATCAAG GAGCGCAAGT GCCTGCTCCT CAAGATCCGC GGTGGGAAAC AGTTCATTTT GCAGTGCGAT AGCGACCCTG AGCTGGTGCA GTGGAAGAAG GAGCTGCGCG ACGCCTACCG CGAGGCCCAG CAGCTGGTGC AGCGGGTGCC CAAGATGAAG AACAAGCCGC GCTCGCCCGT GGTGGAGCTG AGCAAGGTGC CGCTGGTCCA GCGCGGCAGT GCCAACGGCC TCTGACCCGC CCACCCGCCT CCAGGAAGCT ACCTGGAGGA GGTGAGTCTT AGCGGATGAG 40 TAGGAGTTGT CCACGGAGGA AGGTACACAG AAGGGCTTCC AGGCCCAGGA AACAGCAGAG GCACAGAAGT GAGAATGGGT GGGTGAGT-TG GTGGGGAAAC TCCAGGTGCA GAGGATGGTA GCGAAACAAA CTGGAGCATT AAGGTCCAAG TCCTCCAAGA TCTTGACTTG CAGATTAAGG AGTTTGTTCA CCTAATCTGC TTTGGGCAGA GTGTGGTGAG TCCTAGAGAC CCCTCTAGGT CTCTCCTCTC AGTAGCCCCA GAAGGCCTGG AGAGCTGCTT CTGGGTGCCA AGCAGGCAGT GACTCCATCA GATCTAGATT TGGGAAAAGC ATCCCTGGTC AGGGCCTGCA 45 TCAGGGCAGT GGCTGGCCAT GAGGACCCTG AGAAGTAGAC AGATTCACGG AGATTCTCAG GAGGCCAGAC AGGAGACTAT GGTGACAAAT TAGATTAGAG AAGGGGAGAG AATGAAGGAG CAGTTGGGGT AAAAGAAAAC TGAGGCTGAC ATGGGTATAT GGGTGGCGAG TGACTCACCA CCCACTGAGA GGAGAACCTC ACAAGCTCTG ACATGCTCTG GTTCCAGGTT CTGITGGGGC TGATCCAAGA TGGTAGCCTA GAGGTGCACA GAGATGGGGG CCTTGCTTTG CAAAAGGATG CTGGCTGCTG GCCCACAGCA TGGTAATGAG ATTTGAGCTT TATGTGCCCA 50 GGGCTGGGAG GAGGGTCCTG TCACTTTGAA AGCAAAGAGA GGCTCTAGAG AGGGGCATGT TGAGATAGGA ATGCTGCCTT GAGACACCTG GCTTTCCCCA CTCTGGGTGG CTCTCAGCAG GGTGGGTTTC CCCTGCCAGG CAGCACTGAA CCTCTGTGCG CTTCCGGCTG GGAGAGTTTT TACCGTAACT ACATGTGGAA CCATCCTGAA GGAACATCTG GATGGGATGG GGTACAGGGA AGGGAGCTGC CAAGAGTGCT GGCCAGGGAC CTGGGTCTAT GAGCTGGTTG GGGGGTGGGG TTGGGTGCAG GGTACTTGAT CCTGAGTGGG CCTTCTGCGG CCAGGATTGG 55 TTCTAGAGTA GGAGGGGTGG GATCGGGGAT GGGGGAAGCC TGTAACTGCG CTGCAGTTGT CAGGTCCCAG GTTCTGGGTG ACCTACTAAG GATTCTGGGT CCAGTGTGGG TCCCAGGTTA GACGTCCTAG TCCTGAGTCC GTGTCCACAG TTCTGGGTGT TGAGTCTAGG ACAGTGATCT GGAGTTGACA GTCCAATCTA GGTCTGAGTC CTGACCCCAA GTCTAGAGTT CAGGGTCATG GTAGTAGCCT AGGGTCAGAA TCAAGGTTGG GGTCAGTAAC CAGGATGGGA TCGAGGTCAT GGTCCAAAAT CTGGATCTGG GGACCTGTTG GGGGTCTGAG GTGAGTGTCG 60 CAGTCTGGGT ATGGCGTTGG AGACCCAGGG CTGTGATCTG AGGTCATGGT TAGAGTCTCA GGTGGTGGGC CAAGGTTTGA GTCTGGGGTC CTGTTTGGAG TCTGGTGTCA GGTCGTGGAC TGCGTCCAAG GTCAGGGAGT CCGGGGTTAT AGCCAGGGTC TGAGATGAAA GTCCCAGATG GTGTTCAGAG GTCTGAATCT GTGTCTTGGT GAGCGTCCAG GTTCCCTGTG ATCACGTTTG GTGTCAGGGC TGCGGCCCGA CTGGGGAGCC TGGGATCCAG AGATGTGACC CGAGGTTGTG GTCAGAGAAT GGGTCTCGGG TCGTCTTCGT GCCGGGTCCC TGTCGTGTTC 65 CAGGCCCGGG TCTCCGTCCA GCATCGAGGG CCGAGGTCAC GGCCAGGGTC TGAGCCCGCG GTCGCAGGTC TGGTTCGGGG TCAGATTCCG CGCGGCCTCC AGGGGGCGCC GTCGCCGCCC GGCTCGGCCC CTCGCGGGCT WO 00/62736 PCT/USOO/08020 50 CGCTGGCGTT GTGCGCGGCA GGCGGGGCCG GAGGCGGCGG CGGCTCCGGG GGCGCGGGCC GGGCGGCGGC GGCGGCGGCG CCCCGACTGC AGTCCCGGCG GGAGCGGAGC GCGAAGCGCG GGGCCGGGCC CGGAGCCGGC GCCATGGGGC GGCGCCGCCT GTGAGCGGCG GCGAGCGGAG CCGCGGGCGC CGAGCAGGGC CAGGCGGGAG CGTCGGCGCC CGAGGCCGAG CGAGCCGCGG CCGGGCCGGG CCGAGCGCCG AGCGAGCAGG AGCGGCGGCG 5 GCGGCGGCGG CGGCGGGAGG AGGCAGCGCC GCCGCCAAGA TGGCGGACCT GGAGGCGGTG CTGGCCGACG TGAGCTACCT GATGGCCATG GAGAAGAGCA AGGCCACGCC GGCCGCGCGC GCCAGCAAGA AGATACTGCT GCCCGAGCCC AGGTGAGGAG AAGCT TCCCAGTTAA TACATAATCA ATATGCAATF TATFAATACA TCTCTCCATG TCCACTCCCC CTGTATC I1G CCATTYGA CCTGCAMTC CATCCTCCTT ACCTTCCCTA GAGGCCAACT CAT~CT17 GAAAAACCTG GCATTCCCA GAAAAAAAAG TGAAGGGCTG GGAGCTGTCC 10 GTTGTCCTGA TI17GCTCCCT CTGCCCTTGC TFTCCAAATGT GGTTGGAAAG AAGCACTA'IT GAAAAATCCC TAAACGCACC CCTGCAGGGT TGGCTCTACC CTGTAGCCAT GGACACATGC TGTrGATACC ACCTGCCTCA TGAGTCTCAC ATAAIT1TGCC C'TICACACT ATCTACCCCA TCAGCCTTAC CAAAACCATA CCTGCATCCT GGGCAGCATC TGCCCTI'CAA GAGACTAAGG AATCTCCTTG CAACCAAGAA TGACTAGACC AATGAGACAC CCTTTAAGGC CCCAGCACAA TATAGAAATC CCACAATATG GTAATCCCAG TAAGGAGCTA TCAAGCCATr 15 GCAGGACCAT CTAGAATACA ACTAGAGTAT AG'ITCC'=fC AATCCAGGAA CTATACTCTA ACAGCTT1GGC TCACAGGAAC CAGAAGTGAA GATGATGAGG ATCAGGGCTG AGCCTGTGAG CACCAGCTCC ACCACTGACA CCAACCACAG ATFAAACAAG CATCTTGTGG ACCCCTGGGA TGGAAAGAAT AGTTGTTGCC TTATCAACCT CCCCCACAGC CCACACAGAA AAGATAAAAT CATCATGGCT ACAGTGnIAC AGAAGATGAT GACCCAAGGA GTAGGCCTGC CTGAGTGAAT GCTGAGAGTG ATAATGGGAG CAGTAGCATC TCAGAGACTA CAGCAGAAAC 20 CATGCACATA AAGAGC'TTFG CCCAAACYJA TGATAAAGGG CACCCTCAGA GACTCTCCCT AC1TTrAATAT TAGCCCATL1G CAGAAATGGT GAGTGGAAAG AGAAATCTJ7A GGAAGAACCC CTTAAAAAAG CAAAATGC'I1 TTTfAGGTITG TGCTGAAGAG CCTGGAAAAG AAATAAGGAC ACACACGCTG AGAAATCTTC CTCCTGCCCC AACACTGGGA TAATCTCCAA GGATCTCTCC ATATCTCAITr CTCCTGGATA CACTGTCCAC TCAGAAATAT TGTGCAGAGT GCAGTAAYI7C AAAAGTGAGC TA'ITGTG'TrA GGAGTGAAGG CAAGAGTATC GTAAAATAAA 25 TCAAKITTTGA AATGAATTCT CTI'AAA~rGC TTTATAGATG =PAATGTAA GCCAGCAGCT ATTAAACGAT AAACCTTAAA TrCGAGAAAA AC ITGGTCAT TCAGAAACTA TAGAAACAGG CAGGACTrAT TGCGAGGGCA AACACAGAGT GAGCTCCAGC CTGCTrCAGG AAAATCTGCC AGTGCCATGA AGGATGTACT CTGTCTGCTC CACTGCACTA CTGCTCAGTA TGAGCCCATG CCATCAGCTG TCCCTGACCC ACAGGAG FTC 1TTAGAAGAG ACTGGTCAAC AAAAG ITTCT AGGGTGT'= ATACCTGCCA ACTCGAGGGT TAAAACAAGT TGCATAGAAA 30 TGCTCAATCA AGAAAGACAC AGTCA'TACT CAGAGAATAA TAAACAGCCT GGCAGCACAT GAATGAATAG AAAAAAGATG 'TrACATGCAA AGCATGAAAT AACCAAATTC CATAACAGAT GTI'AATCTGT AATGTGTIA GGAGAA'TTTA GAGGAAGTAT AAGAMTT~ C'I=CATCAA AAAAATrATA GCCAATGAGG ATATATCTAT CAATYrATCCA TCAAGTGGTG ATATGGCAGC ACAAGGTAAA ACACAAAGGA ATAAAACCAA CGTPTAT7AA GAACCAATCA TGTGGCA'TTr CACA17GAGC ATCATA1TTA ATTCTGAAAA AAATCCTTGT ACTGTATCAT 35 TCTTCATATFr TTATGGATGC AGTAACTAAG GCTGAGAAGT TTAAAATTTT TCCTAAGTTC AGACACATAG CTAAGTGGCA GAACCAAGAT TCAAACTCAC CCCATCTAAC TGCAGAGCAA ACTGCATGCC TTAAATGTCA AAGTGAATAC TAGCACAGTT AATACAATGT TTGGAAACTC AGAGAAGGAA TGATCCCTCT GCA FFATAGT TACTAAGGAA TCATTGCCAT TATrFAAATG CCAGTGCTrC TACATCAGGC CCAAATT1C TGTCCTACTA ACTGTGAATC AAG3ACTTGAT TCAACCTCTA CTI7GAGTATC TGCCGCAATG AGAAATCACT TACCTCCACT 40 AACCACACAT 'PTAITATA ACAACAGATT G'rTAGTAAGT cc'TTTrAT ACATACTCAA CAGCTGCTTC CCAAGATGCT GTAGGATT1AT GTCTAGAGTC AAACTAGCCA GAAGCAATGT CCAAAATACA CCATAACACT GTGCAGCAAA GGTCCTACTA CCACT7GT GGCCCAAACA TTCTAGGCAG CACTGGATAT CTGAATCATC AATFATTCC ACAAACACTG ACCCCTCTAC CAGTCACCCT CACTAGAAGA ATTAAflCCA CATGATAATA GCTCCCTCAT G ITACTCCCT TCTAAGTCAA ATTGTACACC CCTITATCTG ATTAACAGAG TCTAAGTCAC 45 ATGACCTAAA TGCAAGAGAA CTGGGAATGG ACG'TrGTGG ATTCTACCTT AGTAAGGCAA AGTTATCA FT GGGAATrCCT CTAATACAGG AAGGGTGTTC CAGAGACATT AAGGAGCCAT ATAAATGGAA AATGTCCACT ACAATCCATC ACTTFGGTTGC CCCACATCAA CATTCATTCT TTTGCCACAC TTAAAG FJTC CAAGAACAAA AATTIATCCCA CTGAACATAA TC'1ACTAT C'TITTATATA AAGGAAAATT AGACTI'GACT CAGCAGAACT GAAATAACCC AGCTCTAACA GTTACTGCFl TTAACTCAA GTACTGTGTC TCTAGGTGAT ACCTGCTCCA 50 ACAATAGT11T GGTCACATTT TCAATTGAT ATTCTCTAGT CTCCCAACTT GATAACTGTA CCCTAAACCA TAAAGYFCAC TACCAACATG CTATATATAA AATAACCAAA GGGGGAAGAA GAAAGAGAAA AAGGAAATCT CTTAAAATAC ACAGGTATAC ATATGACAAA GCAAAGAAGG AAATGTGAGC AGATAGTGCA GTCCTCGTrT CTGAAATT1GG TCCCCTGACT GGGGCTATAC CTATCCA'rr TCCTCACCCT CAGCCAGGCA GGTGGAGCAA AAACTrAAGT =TGGTGGAT CTGAATC11G ATGCTGTGGA GCTGTCTTAC TAGCCCCAGA CTACCTGCCT 55 CTCAA'TTCT AATATATCA GTGAAAGCAA ACAGCTITGA TGTI17AAG CCTCTGATrT MIIGGTCTAA CTGATGTAAG ACCACAAGGA CAAGAGTTCT CCAGCTCCGG A TrCTCTTrCT GTTCTGTTAA TGGTGAAATG CCCGAGAGAA GAGYI'GCCAA CTTTGGCAAA TAAAAAATAC AGGATTCCAG TTAAA'rTCAA A'ITAGATAA ACAACAATI' TTTAGTATTA GTGTGTCCCA TTCAATAT GGACATACT-' AACTAAAAAA TGA ITGTTG TTCATCTGAA ATACAAA'TT AACTGGGCAT TCTGAATA FI' CTCTGGCAAC CCCCGAGAGA GTGAAGAAAG 60 TGGTACAAGG ACACTTFAAGA AGACCAGA'rr TGAAAAGACA TTACGGATGT G2TAAATGT CTTA ITCTAG AGAGAGTTAG AGCTGTAGGT AGAACTI1GGG AAATTAAGTT AAAAGCAGAC ACAGAGACCT GGCCAATATA TACTAAGGAG TGGATCACTC TGGTCACAAG CCCAACCTGA GACCAAGGGC ATAGTGAGAT GATVI'GGGAA AGGCACTTAT ACACTACTCA TCCCCGTCI17 TGAACTAAAT GCCTTATAAA TCTCCAAGAG AAATGACAGT CCACCATGTG GACTGCTI'TC TGTAAGTCCA GGGAAAATAA AAGCTATGTG CTrGAAACCC ACTTrCTGATA 65 TTATAAGGTG TGTGATCTTT GTCATGL1AA TGGGTCTGAG TATCAATTCT ACAATTGTAA AGTGACAGTA ATGGTGTGTC CCCAGGTTGT TGTGGAAAGC TTGATTCITrA ATGCAACAGT AGGAAACCCC AGCCTCTCTG WO 00/62736 PCT/US00/08020 51 GAGCAAACAC CCTTCTACAT CTTTACTTCC CCTGCACATT GGCAGGACTC TATTCCTCTA TTTCTCTCTA GTGCTAGAGC AGAAAGGGAC CTTGATTTGA TATCAGGAAA ATCTATTTCT GAACCATAAG CTATGATAGC TGATTTAAAA AATTGACTAT CATGACATGA TAATGATCAT AATGGTAATA CATATTGATA GGGTTGCCGT GAAAGTAATA ATATATCTAA GAGrGTGAC AATATATGAT ACGCCTAGAC TCTCAGAAAA TGCTAATTCC 5 AATCCCAATT GCTCTTTGCA TAAAGTTCTG TCCTAGGGTC TGTTCTTTTC CCACATCTAC CCTCCTTGGA TCTCTCTTCT GTCTTTCA TGTGGTTCAG AGGAGGAGAG AGATCCAGGT CAATGTT CAAATTACAA GGAATTATCA TTTAAATGGG GAAGAAGCTC AAGTTGAC GTGTAGTGGA ATTGGAGTGG AGTGGAGTGG AATGGAAACT AACAGGAAGA CACTGCACAT GGTTAAGATA AAGATTGTTT CCTGAAACCT TTAATGTG CTTACATACT CACACATACA TATGTGCATG CACTGGGACT CTGCAATATG CATTTCTGAC TATGGAACAT 10 AGCCATAAAA GTCTGCAC TGAACGTTCA GTGGGCCTTT CACAAGCTGC CCTAATTGGG AAAGAAAAAC ATGGTCCCTC CATTTCCTGC CCCCAACTCC AGAAAAGTCA CCATAGTTGA GGGTACATCT GAGAAGCCAG CACTTGGGAG TTCAGGGCTC AAGTTCCTTT CTAGAAAAAC ACTGGGTGAT TCTAGGGGAA CTTCCGATCA GAAACAGCCA ATTCAGAGTG AGAGAAGAAA ACGTGACCAT GCAGTTCCTG TGGTTACCAG CCTTGCCCCT CTCTTGCCTT CTGGGAGTTA TAAAACCCAA GACTGGAAAG GAAAACCAGC ATTTGCTCAG GCAGCCTCTC 15 TGGGAAGATG CTGCTTCTTC CTCTCCCCCT GCTGCTCTTT CTCTTGTGCT CCAGAGCTGA AGCTGGTGAG TATCAGGGTT CTTCCCTCTG AAATCTGCAG TATCAGCTCC TGAAACAAAG. ATGTTTAGTC TGAAATAGCT GACTCCTAAA CAGGGTTCCA AGATCTCTCT TCAAGAGTCC CACAGAGGAA ATTTCCACTT GGGATGTGTG CCACCCCACC CCCACCCCCA CCCACTGCCA TTCTCTACAG CCTAGGACAC CCCCAGGAAC AAGGAATTITC ACCTCAATTG TAGAAAAGCC CAGAGCAAGT GGAAGGAAAA GGGGTATCCC CAGGAAAACA GACATGTCCT 20 CTTAATCTTC TGAGCATCAG GGCTACCCAT TACTTTGTGA CTTTCTCACT CTGTGACCAT GCTCAAGAGC TATGGAGAAA TCTAAAACAG GAACCTGGAC AGTGGGTCCT ACACAGAGAC AGAGGAGAGT GGGCCAGGGC AAGGTGGGAG TGGGAGAAGT CTGAGATGAA AACATCAGAA TGGAGCAGAG GCAAGAATGA GATTTCACCT GGGAGGTTAT GGGTGGGGAA AGATACGAAA TACAGGAGAC AGGAGAGGGA AGATGGGCGG AACACAGGGT GAGAATGAGA TTCCAGGGAA GCCTAGCTCA GCTTTAACCC AATTTGTCCA TTCATTGGAG AGAGTATCTA 25 TGGCCGTGTT CAAACCCTGG GGTGCTCTGT TCCAGGGGAG ATCATCGGGG GCACAGAATG CAAGCCACAT TCCCGCCCCT ACATGGCCTA CCTGGAAATT GTAACTTCCA ACGGTCCCTC AAAATGT GGTGGTTTCC TTATAAGACG GAACTTTGTG CTGACGGCTG CTCATTGTGC AGGAAGGTGA GACAACAGGG TCTATTTATC TCCAAATGGG AGATGAACAA CCAGAGTAGC ATCCAGGAAT ACACCTGCAC TGGGGACTGA AGAGGGGGTC CTGGGTCTTG TCAACTTTCA GGAGAGGGAA GACTTTGGGC TGAAAGACTT TAGTCTGTGT TTGAATAGTT 30 CCTTGAGCCT CAGTCACTGA GCTAAGCTCC CTTCGGAGGA AAAGGAGGTC CTGTCCGAAG GTCCCTCTTG TTGCAGTAGC ACCCCTCACC CCTACCCAAC TCAAGACACA CGGCTCACT7 TTCAGGGCCC CACCCAGTCT CAGGGCCACT TCCTCTATGG CCTTTCAAG AACACTGGCT CTAGTTCTCA GGGTCCTGAA CCCATCATTT TATGGGAGCA GAGAACAGGT CTACATAAGA CCCCCACTTT CCCGTTTTAA CTGATATCTC CTGCTTCAGG GGCTGGCCCT CATGCAGGGT TCCCTGAATT AGGAAGTGTG AACCCTGTCC CCTGAGTCCT CCCTGGCCTG 35 TFCAGTCCCC AGCAATTCCA GGGGTCGTAG AAATTGTGTC TGTTTCCTGA GAAAGCTCTT TCATGAGTTA AGCCTGAGCC CTCAAATGCC ACAAGTGGCC CATGAAAAGG GAGATGGGTA GAGTCCGGCN ACCCAGTGAC AGAGTAGT CCTCTTTTCT CAGAATGAGC TCACCTCAGA AGAAACCCCA AGCCATCACT GTCGCCTCCT TTTCCTTCCT TCTTCCTCAC AGCAGGTCTA TAACAGTCAC CCTTGGAGCC CATAACATAA CAGAGGAAGA AGACACATGG CAGAAGCTTG AGGTTATAAA GCAATTCCGT CATCCAAAAT ATAACACTTC TACTCTTCAC 40 CACGATATCA TGTTACTAAA GGTGACAACA CCTCTCTTCT CCCTTTCCAC TTCCCATTCT CCTAAGCTTC TCCTTCAGGT CCTCATTGCC CTGAATTTT CTTAGGACTT GGCTATAACA TGAAGCTACT CACCCTGTCC CTCCCTGATC ACCTCCAACT GTCCAGAGCC CATTTCGAGG ACTGACAGTC CTTCATTCCC TTCACAGTTG AAGGAGAAAG CCAGCCTGAC CCTGGCTGTG GGGACACTCC CCTTCCCATC ACAATTCAAC TTTGTCCCAC CTGGGAGAAT GTGCCGGGTG GCTGGCTGGG GAAGAACAGG TGTGTTGAAG CCGGGCTCAG ACACTCTGCA 45 AGAGGTGAAG CTGAGACTCA TGGATCCCCA GGCCTGCAGC CACTTCAGAG ACTTTGACCA CAATCTTCAG CTGTGTGTGG GCAATCCCAG GAAGACAAAA TCTGCATTTA AGGTGATCCT CCAACTAGGT TTCCTCTCCA AAACTCACTG TTCAGGGACC TGAATGCTCT TAGAAGGAGA TGGGGTCAGC AGGTTGTCAG TCAGGTGACA GGGTGAGCAT CACAGGAATT GCTGTCCTCC CGTGGTCCAA GACAGCCTCT GACCATCCAT TCCAGTCTAC TGCACTGGGG GCATGGGGTG ACTGTGGAGA ATGTGGATGA CGGTCCCAAG AAAGGAAGAA GGGGCATCAG 50 AACTAGATGT ATAAGTGAGG AGCTCCACCT CCTGGGTCTG ACTTTAGGTC TCACTGTGAC TCCAAGCTGG CTGGCAGACA GGAGTGGAGG ACTTCCCGGG CTCACCTTCT TCTCTCTCTC CTCCCCCTAC AGGGAGACTC TGGGGGCCCT CTTCTGTGTG CTGGGGTGGC CCAGGGCATC GTATCCTATG GACGGTCGGA TGCAAAGCCC CCTGCTGTCT TCACCCGAAT CTCCCATTAC CGGCCCTGGA TCAACCAGAT CCTGCAGGCA AATTAATCCT GGATCCTGAG CCAGCCTGAA GGGAAGCTGG AACTGGACCT TAGCAGCAAA GTGTGTGCAA CTCATTCTGG 55 TTCTACCCTT GGTTCCCTCA GCCACAACCC TAAGCCTCCA AGAGGTCTCC TACAGGTAAC AGAACTTTCA ATAAACTTCA GTGAAGACAC AGCTTCTAGT CGTGAGTGTG TGTCCCTCTC TGCTGCTCTC TTCTCCTGCA CATGTGACCT GATTCCCAGC CCAAGCACCA AGGA CACCGCTCCT GTCAGCCAAC AAATATCCAT TGAGCGACAC CTGTGTCCCA GGTGCTGCTC TGGGCCCTGG GAGAAGTGCA TCAGTGGGCT TGGTAGTAGA GGGTAGGGAT GGAGTGAAGG GTAGGCAGGA AGAATGTCCC CAGGCTGGTA GGAGGTGGGG TGGGGGGT 60 CAGTCTCAAA ACTCCCATGA AAACCAGAGA GAAGTTTCAG AACTCCACCC AAGAGGCTGG GTTTCTAGGG CCCAGAGCTG CCCTCCCCCA CCCTAGAATG GGCTATAAAA GTCCCTTCCC AGCTACGTCC AGAGAAGAGC TGGAGGAAGT GAGAGGTCGG CTGGGGGTCC TCAAAGTGAG AGGGGAGCAG AGGATCCTCC CGTGCAGGCT GTGGATGTCA CTCACTTCCC AGCTGGTGAA GCCTCGCTGC AGAGATGCAT CTGCTCCCAG CCCTGGCAGG GGTCCTGGCC ACACTCGTCC TCGCCCAGCC CTGTGAGGGC ACTGACCCAG GTAATAGTCC CCTAGACAGG 65 CAAGGAGGAG GGAGGGGAAA TGGAAGGGGA AGCACTTGGG TCTTGGAGGG GGTCTTGTGG CTTGCTGAAC CCTGAGTCCC CATCTCTG AACAGCCTCC CCTGGGGCAG TGGAGACCTC GGTCCTGCGA GACTGCATAG WO 00/62736 PCT/USOO/08020 52 CAGAGGCCAA GTTGCTGGTG GATGCTGCCT ACAATTGGAC CCAGAAGAGG TGGACTTGGG TCTGGGGGCT GCATGGGCCT GGGAGGATCA GT TAATACCTTG TGGGGTCAGG GAGCCCATGT CCCGTGCTGA TGTTATTTCC CCACCAGGTC CGGGCTGTCT CCAACCAGAT TGTGCGCTTC CCCAATGAGA GACTGACCTC CGACCGTGGC CGAGCCCTCA TGTTCATGCA GTGGGGCCAG TTCATrGACC ATGACCTGGA CTTCTCCCCG GAGTCCCCGG 5 CCAGAGTGGC CTTCACTGCA GGCGTTGACT GTGAGAGGAC CTGCGCCCAG CTGCCCCCCT GCTTCCCAT CAAGGTACCT ACCCTCAGCC AATCTCCCAT GCCCTTGTGT GGCCTCCCCC AAAGGCAAGG TGCTGGGGGT GGGGATCTGG AAGACTGGAG CACCATCCTT AAGGAGCTGC CTGTGGAGCT AGGGTATGAG ACAGAGACAC AAG CACTGTCTCC TCTTCCATCT CAGATCCCAC CCAATGACCC CCGCATCAAG AACCAGCGTG ACTGCATCCC TTTCTTCCGC TCGGCACCCT CATGCCCCCA AAACAAGAAC AGAGTCCGCA ACCAGATCAA 10 CGCGCTCACC TCCTTTGTGG ACGCCAGCAT GGTGTATGGC AGTGAGGTCT CCCTCTCGCT GCGGCTCCGC AACCGGACCA ACTACCTGGG GCTGCTGGCC ATCAACCAGC GCTTTCAAGA CAACGGCCGG GCCCTGCTGC CCTTCGACAA CCTGCACGAT GACCCCTGTC TCCTCACCAA CCGCTCGGCG CGCATCCCCT GCTTCCTGGC AGGTCAGACA GGGAGGAAGG TGGTGTCTTC CCAGGAAACA GCCATCCCTG GGGTCCCAAC TGGGAAGCAA TGGTGGGATG TGGTGAAGGT ACATGGTTG GGACCTCAGT ATTAGGCACA CCATAAGCAT GGATCTGTGC AC 15 TGAAGAGATG GAGGTCCAGT GAGGGCCAGG AGTTTGGCCC ACCCCGTCTC TCCCATCCCC AGCCCTGGGT CTACCCTGGT AGAAAGACAT TTCTCTGGGA AAGGCTGCAG TAAATCTGAG CTTGGGGTTr TCAAGGTGAC ACCCGATCAA CGGAAACCCC CAAACTGGCA GCCATGCACA CCCTCTTTAT GCGAGAGCAC AACCGGCTGG CCACCGAGCT GAGACGCCTG AATCCCCGGT GGAATGGAGA CAAACTGTAC AATGAGGCTC GGAAGATCAT GGGGGCCATG GTCCAGGTAA GGAGCTCTGC ATCCCAGCAT CCCCC CTTTGTATCT CCACCCACCA 20 ATAGTAAATT AATGTTGTCA CATTTGACGT GATGACAATA AAGAATATGT CTGAGCCACC CTTTGAAAAG GCAAGGGTAT GGGTGAGTAG CCTCTGGGGA ATGTTCCTCC TGTCTTCCCT TCCAGATCAT CACCTACCGA GACYTCTGC CCCTGGTTCT GGGCAAGGCC CGGGCCAGGA GAACCCTGGG GCACTACAGG GGGTACTGCT CCAATGTGGA CCCACGGGTG GCCAATGTCT TCACCCTGGC CTTCCGCT GGCCACACAA TGCTCCAGCC CTTCATGTTC CGCTTGGACA GTCAGTACCG GGCCTCCGCA CCCAACTCGC ATGTCCCACT TAGCTCTGCC 25 TTCTTTGCCA GCTGGCGGAT CGTGTATGAA GGTGACCAGG TTTTCCAGGG GGCAAATGGG GGTGAGGGTG GGGAGCATGC CCTCCCCTAG GTGG TCCAGCTGCT TCATGTCTCT CCAGAACTCT GTTTCCTGAC AAACGTTACT AACATACCCG ACTGGCTTGT CCAGCTCTGG GCTAGCTTGG CATCATGTGA TAACCCAAGT AGCTTCCCAG AGGCTGGTCC AATCTGTGCT GCTCACATTC CCTGCCACCA GGGGGCATCG ACCCCATCCT CCGGGGCCTC ATGGCCACCC CTGCCAAGCT GAACCGTCAG GATGCCATGT TAGTGGATGA GCTCCGGGAC 30 CGGCTGTTTC GGCAAGTGAG GAGGATTGGG CTGGACCTGG CAGCTCTCAA CATGCAACGA AGCCGGGACC ACGGCCTTCC AGGTGAGGGG GCTGTCCACC TCTTCTCCCA GCTTTGCTCG GGCCAGGCTG CTCAAGGGGT TCTGGGAAGA CCCTGGTACC CGACTGCCTG GTAGGTTCTG GTGGCAGAAA CGAGGTGTTT TCACCAAAAG ACAGCGCAAG GCCCTGAGCA GAATTTCCTT GTCTCGAATT ATATGTGACA ATACCGGTAT CACCACGGTT TCAAGGGACA TCTTCAGAGC CAACATCTAC CCTCGGGGCT TTGTGAACTG CAGCCGTATC CCCAGGTTGA 35 ACCTATCAGC CTGGCGAGGG ACATGAGGCT TCTGCAGGTA AGGGGAGGCC ACCTCCAGCA CCCTGGGCTG GTTAAGCCTC ACATCCTTCC CTGGATGGAT GGCTGAGTCC TCTTAGGTCT CTAAGCAGAG AAAACAGAAC TTGTCACTAG GTACTCTTC CAAGTGGCTT CCCAATGTGC TAGTTTCTGG GCTGACAGTC AATTCCAGGC CCTAGGACTT TGGGGGGAAA TTAGGAGCAT CCAACTA GAATTCCGTG GCCAGGACCC CTGCCAGGGC ACTGACCCAG CCTCCCCTGG GGCAGTGGAG ACCTCGGTCC TGCGAGACTG CATAGCAGAG GCCAAGTTGC 40 TGGTGGATGC TGCCTACAAT TGGACCCAGA AGAGCATCAA GCAGCGGCTT CGCAGCGGTT CAGCCAGCCC CATGGACCTC CTGTCCTACT TCAAACAACC GGTAGCAGCC ACCAGGACAG TTGTTCGGGC CGCAGATTAT ATGCATGTGG CTTTGGGGCT GCTTGAAGAG AAGTTACAAC CCCAGCGGTC CGGACCCTTC ATTGTCACTG ATGTGCTAAC AGAACCACAG CTGCGGCTGC TGTCCCAGGC CAGTGGCTGT GCTCTCCGGG ACCAGGCCGA GCGCTGCAGC GACAAGTACC GCACCATCAC TGGACGGTGC AACAACAAGA GGAGACCCTT GCTAGGGGCC 45 TCCAACCAGG CTCTGGCTCG CTGGCTGCCC GCCGAGTATG AGGATGGGCT GTCGCTCCCC TTCGGCTGGA CCCCCAGCAG GAGGCGCAAT GGCTTCCTTC TCCCTCTTGT CCGGGCTGTC TCCAACCAGA TTGTGCGCTT CCCCAATGAG AGACTGACCT CCGACCGTGG CCGAGCCCTC ATGTTCATGC AGTGGGGCCA GTTCATTGAC CATGACCTGG ACTTCTCCCC GGAGTCCCCG GCCAGAGTGG CCTTCACTGC AGGCGTTGAC TGTGAGAGGA CCTGCGCCCA GCTGCCCCCC TGCTTrCCCA TCAAGATCCC ACCCAATGAC CCCCGCATCA AGAACCAGCG 50 TGACTGCATC CCTTrCTTCC GCTCGGCACC CTCATGCCCC CAAAACAAGA ACAGAGTCCG CAACCAGATC AACGCGCTCA CCTCCTTTGT GGACGCCAGC ATGGTGTATG GCAGTGAGGT CTCCCTCTCG CTGCGGCTCC GCAACCGGAC CAACTACCTG GGGCTGCTGG CCATCAACCA GCGCTTTCAA GACAACGGCC GGGCCCTGCT GCCCTTCGAC AACCTGCACG ATGACCCCTG TCTCCTCACC AACCGCTCGG CGCGCATCCC CTGCTTCCTG GCAGGTGACA CCCGATCAAC GGAAACCCCC AAACTGGCAG CCATGCACAC CCTCTTTATG CGAGAGCACA 55 ACCGGCTGGC CACCGAGCTG AGACGCCTGA ATCCCCGGTG GAATGGAGAC AAACTGTACA ATGAGGCTCG GAAGATCATG GGGGCCATGG TCCAGATCAT CACCTACCGA GACTTTCTGC CCCTGGTTCT GGGCAAGGCC CGGGCCAGGA GAACCCTGGG GCACTACAGG GGGTACTGCT CCAATGTGGA CCCACGGGTG GCCAATGTCT TCACCCTGGC CTTCCGCTTT GGCCACACAA TGCTCCAGCC CTTCATGTTC CGCTTGGACA GTCAGTACCG GGCCTCCGCA CCCAACTCGC ATGTCCCACT TAGCTCTGCC TrCTTTGCCA GCTGGCGGAT CGTGTATGAA 60 GGGGGCATCG ACCCCATCCT CCGGGGCCTC ATGGCCACCC CTGCCAAGCT GAACCGTCAG GATGCCATGT TAGTGGATGA GCTCCGGGAC CGGCTGTTC GGCAAGTGAG GAGGATTGGG CTGGACCTGG CAGCTCTCAA CATGCAACGA AGCCGGGACC ACGGCCTTCC AGGGTACAAT GCTTGGAGGC GCTTCTGTGG GCTCTCCCAG CCCCGGAATT TGGCACAGCT TAGCCGGGTG CTGAAAAACC AGGACTTGGC AAGGAAGTTC CTGAATTTGT ATGGAACACC TGACAACATT GACATCTGGA TTGGGGCCAT CGCTGAGCCT CTTITGCCGG GGGCTCGAGT 65 GGGGCCTCTT CTGGCTTGTC TGTTCGAGAA CCAGTTCAGA AGAGCCGAGA CGGAGACAGG TrCTGGTGGC AGAACGAGGT GTTTCACCA AAGACAGCGC AAGGCCCTGA GCAGAATTTC CTTGTCTCGA ATTATATGTG WO 00/62736 PCT/USOO/08020 53 ACAATACCGG TATCACCACG GTTTCAAGGG ACATCTTCAG AGCCAACATC TACCCTCGGG GCTTTGTGAA CTGCAGCCGT ATCCCCAGGT TGAACCTATC AGCCTGGCGA GGGACATGAG GCTTCTGCAG GAGTCTATCC CAAGTCTCCA ACTTTTGGAG ACAAGGGGAA GGGGAGGACC ATGAGGCTGC CTTGTCTCCC TGGAGCAAGT GCAGGCTCGT GACGCTTCTG CTGGCTACAG CTCAGAGCTG GGTTCCCCAG CCAGGAGTGA AGGCTGGGGG 5 CTCCTATCAG CAATGGACCT TCCGCCTTGG GAGCCTCTTA GGTATTAGGC TATGAATCAG CGCCACGTGC AAAGGCTTGG GAGCCAAGCC ATGTGGTCTT GCACCCCAGG CAAGAAAAGT. CAGCTGGAGG GTTTACAGCA CTTCTACTG TTTCCCAGCC CTCCCTCCCC TCCCTCACCA TGACTAAGAG ACCACTCGGT CCTAGCCTCC AGACACCCCA CAATACTCCT CTGAGCCTGA GGCCAGGCAG CATGCTCTGC TTCTACCAAT AAAGCACTGC CGGAATTC CATATGTATG GGAATACTGT ATTTCAGGCA TTATAAGGAA TGAAATTATA GGCCGGGCAT 10 TGTGGCTAAC CCTTGTAATC CTAGCACTTT GAGAGGCTGA AGTGGGCAGA TCACTTGAGC TTCAGAGTTC GAGACCAGCA TGGACAACAT GGTGAAACCC AGTCTCTACC AAAAACACAA AAATATTAGC TGGGTGTGGT GGTGCATGCC TGTAGTCCCA GCTACTCAGG AGGCTGAGGT GGGAGGATCG CTTGAGCCTG GGAGGCAGAA GTTGCAATGA GCAGAGATCG TGCCACTCCG CTCCAGTCTT GGTGACAGAA TGAGACTCCA TCTCAAAAAT AAATAAATAA ATAAATAAAA TAAATGAAAT GAAATTATAA GAAATTACCA CTITTTCATG TAAGAAGTGA 15 TCATTTCCAT TATAAGGGAA GGAATTTAAT CCTACCTGCC ATTCCACCAA AGCTTACCTA GTGCTAAAGG ATGAGGTGTT AGTAAGACCA ACATCTCAGA GGCCTCTCTG TGCCAATAGC CTTCCTTCCT TTCCCTrCCA AAAACCTCAA GTGACTAGTT CAGAGGCCTG TCTGGAATAA TGGCATCATC TAATATCACT GGCCTTCTGG AACCTGGGCA TTTTCCAGTG TGTTCCATAC TGTCAATATT CCCCCAGCTT CCTGGACTCC TGTCACAAGC TGGAAAAGTG AGAGGATGGA CAGGGATTAA CCAGAGAGCT CCCTGCTGAG GAAAAAATCT CCCAGATGCT 20 GAAAGTGAGG CCATGTGGCT TGGCCAAATA AAACCTGGCT CCGTGGTGCC TCTGTCTTAG CAGCCACCCT GCTGATGAAC TGCCACCTTG GACTTGGGAC CAGAAAGAGG TGGGTTGGGT GAAGAGGCAC CACACAGAGT GATGTAACAG CAAGATCAGG TCACCCACAG GCCCTGGCAG TCACAGTCAT AAATTAGCTA ACTGTACACA AGCTGGGGAC ACTCCCTTTG GAAACCAAAA AAAAAAAAAA AAAAAAGAGA CCTTATGCA AAAACAACTC TCTGGATGGC ATGGGGTGAG TATAAATACT TCTTGGCTGC CAGTGTGTTC ATAACTTTGT AGCGAGTCGA 25 AAACTGAGGC TCCGGCCGCA GAGAACTCAG CCTCATTCCT GCTTTAAAAT CTCTCGGCCA CCTTTGATGA GGGGACTGGG CAGTTCTAGA CAGTCCCGAA GTTCTCAAGG CACAGGTCTC TTCCTGGTTT GACTGTCCTT ACCCCGGGGA GGCAGTGCAG CCAGCTGCAA GGTGAGTTGC C CATATGTATG GGAATACTGT ATTTCAGGCA TTATAAGGAA TGAAATTATA GGCCGGGCAT TGTGGCTAAC CCT7GTAATC CTAGCACTTT GAGAGGCTGA AGTGGGCAGA TCACTTGAGC TTCAGAGTTC GAGACCAGCA TGGACAACAT GGTGAAACCC AGTCTCTACC 30 AAAAACACAA AAATATTAGC TGGGTGTGGT GGTGCATGCC TGTAGTCCCA GCTACTCAGG AGGCTGAGGT GGGAGGATCG CTTGAGCCTG GGAGGCAGAA GTTGCAATGA GCAGAGATCG TGCCACTCCG CTCCAGTCTT GGTGACAGAA TGAGACTCCA TCTCAAAAAT AAATAAATAA ATAAATAAAA TAAATGAAAT GAAATTATAA GAAAT7ACCA CTTTTTCATG TAAGAAGTGA TCATTTCCAT TATAAGGGAA GGAATAAT CCTACCTGCC ATTCCACCAA AGCTTACCTA GTGCTAAAGG ATGAGGTGTT AGTAAGACCA ACATCTCAGA GGCCTCTCTG 35 TGCCAATAGC CTTCCTTCCT TTCCCTTCCA AAAACCTCAA GTGACTAGT7 CAGAGGCCTG TCTGGAATAA TGGCATCATC TAATATCACT GGCCTTCTGG AACCTGGGCA TITTCCAGTG TGTTCCATAC TGTCAATATT CCCCCAGCTT CCTGGACTCC TGTCACAAGC TGGAAAAGTG AGAGGATGGA CAGGGATTAA CCAGAGAGCT CCCTGCTGAG GAAAAAATCT CCCAGATGCT GAAAGTGAGG CCATGTGGCT TGGCCAAATA AAACCTGGCT CCGTGGTGCC TCTGTCTTAG CAGCCACCCT GCTGATGAAC TGCCACCTTG GACTTGGGAC CAGAAAGAGG 40 TGGGTTGGGT GAAGAGGCAC CACACAGAGT GATGTAACAG CAAGATCAGG TCACCCACAG GCCCTGGCAG TCACAGTCAT AAATTAGCTA ACTGTACACA AGCTGGGGAC ACTCCCTTTG GAAACCAAAA AAAAAAAAAA AAAAAAGAGA CCTTTATGCA AAAACAACTC TCTGGATGGC ATGGGGTGAG TATAAATACT TCTTGGCTGC CAGTGTGTTC ATAACTGT AGCGAGTCGA AAACTGAGGC TCCGGCCGCA GAGAACTCAG CCTCATTCCT GCTTTAAAAT CTCTCGGCCA CCTTTGATGA GGGGACTGGG CAGTTCTAGA CAGTCCCGAA GTTCTCAAGG 45 CACAGGTCTC TTCCTGGTTT GACTGTCCTT ACCCCGGGGA GGCAGTGCAG CCAGCTGCAA GGTGAGTTIGC C CTGCTTTAAA ATCTCTCGGC CACCTGAT GAGGGGACTG GGCAGYrCTA GACAGTCCCG AAGTTCTCAA GGCACAGGTC TCTTCCTGGT TTGACTGTCC TTACCCCGGG GAGGCAGTGC AGCCAGCTGC AAGCCCCACA GTGAAGAACA TCTGAGCTCA AATCCAGATA AGTGACATAA GTGACCTGCT TTGTAAAGCC ATAGAGATGG CCTGTCCTTG GAAATTTCTG TTCAAGACCA AATTCCACCA GTATGCAATG AATGGGGAAA AAGACATCAA 50 CAACAATGTG GAGAAAGCCC CCTGTGCCAC CTCCAGTCCA GTGACACAGG ATGACCTTCA GTATCACAAC CTCAGCAAGC AGCAGAATGA GTCCCCGCAG CCCCTCGTGG AGACGGGAAA GAAGTCTCCA GAATCTCTGG TCAAGCTGGA TGCAACCCCA TTGTCCTCCC CACGGCATGT GAGGATCAAA AACTGGGGCA GCGGGATGAC TTTCCAAGAC ACACTTCACC ATAAGGCCAA AGGGATTTTA ACTTGCAGGT CCAAATCTTG CCTGGGGTCC ATTATGACTC CCAAAAGTT GACCAGAGGA CCCAGGGACA AGCCTACCCC TCCAGATGAG CTTCTACCTC 55 AAGCTATCGA ATTTGTCAAC CAATATTACG GCTCCTTCAA AGAGGCAAAA ATAGAGGAAC ATCTGGCCAG GGTGGAAGCG GTAACAAAGG AGATAGAAAC AACAGGAACC TACCAACTGA CGGGAGATGA GCTCATCTTC GCCACCAAGC AGGCCTGGCG CAATGCCCCA CGCTGCATTG GGAGGATCCA GTGGTCCAAC CTGCAGGTCT TCGATGCCCG CAGCTGTTCC ACTGCCCGGG AAATGTTTGA ACACATCTGC AGACACGTGC GTTACTCCAC CAACAATGGC AACATCAGGT CGGCCATCAC CGTGTTCCCC CAGCGGAGTG ATGGCAAGCA CGACTTCCGG 60 GTGTGGAATG CTCAGCTCAT CCGCTATGCT GGCTACCAGA TGCCAGATGG CAGCATCAGA GGGGACCCTG CCAACGTGGA ATTCACTCAG CTGTGCATCG ACCTGGGCTG GAAGCCCAAG TACGGCCGCT TCGATGTGGT CCCCCTGGTC CTGCAGGCCA ATGGCCGTGA CCCTGAGCTC TTCGAAATCC CACCTGACCT TGTGCTTGAG GTGGCCATGG AACATCCCAA ATACGAGTGG TTTCGGGAAC TGGAGCTAAA GTGGTACGCC CTGCCTGCAG TGGCCAACAT GCTGCTTGAG GTGGGCGGCC TGGAGTTCCC AGGGTGCCCC TTCAATGGCT GGTACATGGG 65 CACAGAGATC GGAGTCCGGG ACT7CTGTGA CGTCCAGCGC TACAACATCC TGGAGGAAGT GGGCAGGAGA ATGGGCCTGG AAACGCACAA GCTGGCCTCG CTCTGGAAAG ACCAGGCTGT CGTTGAGATC AACATTGCTG WO 00/62736 PCT/USOO/08020 54 TGATCCATAG TTCAGAAG CAGAATGTGA CCATCATGGA CCACCACTCG GCTGCAGAAT CCTTCATGAA GTACATGCAG AATGAATACC GGTCCCGTGG GGGCTGCCCG GCAGACTGGA TTTGGCTGGT CCCTCCCATG TCTGGGAGCA TCACCCCCGT GTTTCACCAG GAGATGCTGA ACTACGTCCT GTCCCCTTTC TACTACTATC AGGTAGAGGC CTGGAAAACC CATGTCTGGC AGGACGAGAA GCGGAGACCC AAGAGAAGAG AGATTCCATT 5 GAAAGTCTTG GTCAAAGCTG TGCTCTTTGC CTGTATGCTG ATGCGCAAGA CAATGGCGTC CCGAGTCAGA GTCACCATCC TCTTTGCGAC AGAGACAGGA AAATCAGAGG CGCTGGCCTG GGACCTGGGG GCCTTATTCA GCTGTGCCTT CAACCCCAAG GTTGTCTGCA TGGATAAGTA CAGGCTGAGC TGCCTGGAGG AGGAACGGCT GCTGTTGGTG GTGACCAGTA CGTTGGCAA TGGAGACTGC CCTGGCAATG GAGAGAAACT GAAGAAATCG CTCTTCATGC TGAAAGAGCT CAACAACAAA TTCAGGTACG CTGTGTTTGG CCTCGGCTCC AGCATGTACC 10 CTCGGTTCTG CGCCTTTGCT CATGACATTG ATCAGAAGCT GTCCCACCTG GGGGCCTCTC AGCTCACCCC GATGGGAGAA GGGGATGAGC TCAGTGGGCA GGAGGACGCC TTCCGCAGCT GGGCCGTGCA AACCTTCAAG GCAGCCTGTG AGACGTTTGA TGTCCGAGGC AAACAGCACA TTCAGATCCC CAAGCTCTAC ACCTCCAATG TGACCTGGGA CCCGCACCAC TACAGGCTCG TGCAGGACTC ACAGCCTTTG GACCTCAGCA AAGCCCTCAG CAGCATGCAT GCCAAGAACG TGTTCACCAT GAGGCTCAAA TCTCGGCAGA ATCTACAAAG TCCGACATCC 15 AGCCGTGCCA CCATCCTGGT GGAACTCTCC TGTGAGGATG GCCAAGGCCT GAACTACCTG CCGGGGGAGC ACCTTGGGGT TTGCCCAGGC AACCAGCCGG CCCTGGTCCA AGGCATCCTG GAGCGAGTGG TGGATGGCCC CACACCCCAC CAGACAGTGC GCCTGGAGGA CCTGGATGAG AGTGGCAGCT ACTGGGTCAG TGACAAGAGG CTGCCCCCCT GCTCACTCAG CCAGGCCCTC ACCTACTCCC CGGACATCAC CACACCCCCA ACCCAGCTGC TGCTCCAAAA GCTGGCCCAG GTGGCCACAG AAGAGCCTGA GAGACAGAGG CTGGAGGCCC TGTGCCAGCC 20 CTCAGAGTAC AGCAAGTGGA AGTTCACCAA CAGCCCCACA TTCCTGGAGG TGCTAGAGGA GTTCCCGTCC CTGCGGGTGT CTGCTGGCTT CCTGCTTTCC CAGCTCCCCA TTCTGAAGCC CAGGTTCTAC TCCATCAGCT CCTCCCGGGA TCACACGCCC ACGGAGATCC ACCTGACTGT GGCCGTGGTC ACCTACCACA CCGGAGATGG CCAGGGTCCC CTGCACCACG GTGTCTGCAG CACATGGCTC AACAGCCTGA AGCCCCAAGA CCCAGTGCCC TGCTTTGTGC GGAATGCCAG CGCCTTCCAC CTCCCCGAGG ATCCCTCCCA TCCTTGCATC CTCATCGGGC 25 CTGGCACAGG CATCGTGCCC TTCCGCAGTT TCTGGCAGCA ACGGCTCCAT GACTCCCAGC ACAAGGGAGT GCGGGGAGGC CGCATGACCT TGGTGTTTGG GTGCCGCCGC CCAGATGAGG ACCACATCTA CCAGGAGGAG ATGCTGGAGA TGGCCCAGAA GGGGGTGCTG CATGCGGTGC ACACAGCCTA TTCCCGCCTG CCTGGCAAGC CCAAGGTCTA TGTTCAGGAC ATCCTGCGGC AGCAGCTGGC CAGCGAGGTG CTCCGTGTGC TCCACAAGGA GCCAGGCCAC CTCTATGTTT GCGGGGATGT GCGCATGGCC CGGGACGTGG CCCACACCCT GAAGCAGCTG 30 GTGGCTGCCA AGCTGAAATT GAATGAGGAG CAGGTCGAGG ACTATTTCTT TCAGCTCAAG AGCCAGAAGC GCTATCACGA AGATATCTTC GGTGCTGTAT T[CCTTACGA GGCGAAGAAG GACAGGGTGG CGGTGCAGCC CAGCAGCCTG GAGATGTCAG CGCTCTGAGG GCCTACAGGA GGGGTTAAAG CTGCCGGCAC AGAACTrAAG GATGGAGCCA GCTCTGCATT ATCTGAGGTC ACAGGGCCTG GGGAGATGGA GGAAAGTGAT ATCCCCCAGC CTCAAGTCTT ATTTCCTCAA CGTTGCTCCC CATCAAGCCC TTTACTTGAC CTCCTAACAA GTAGCACCCT 35 GGATTGATCG GAGCCTCCTC TCTCAAACTG GGGCCTCCCT GGTCCCTTGG AGACAAAATC TTAAATGCCA GGCCTGGCGA GTGGGTGAAA GATGGAACTT GCTGCTGAGT GCACCACTTC AAGTGACCAC CAGGAGGTGC TATCGCACCA CTGTGTATTT AACTGCCTTG TGTACAGTTA TTFATGCCTC TGTATTTAAA AAACTAACAC CCAGTCTGTT CCCCATGGCC ACTTGGGTCT TCCCTGTATG ATTCCTTGAT GGAGATATTT ACATGAATTG CATACTT TAATC GAATTCCCAC TCTGCTGCCT GCTCCAGCAG ACGGACGCAC AGTAACATGG 40 GCAACTTGAA GAGCGTGGCC CAGGAGCCTG GGCCACCCTG CGGCCTGGGG CTGGGGCTGG GCCTTGGGCT GTGCGGCAAG CAGGGCCCAG CCACCCCGGC CCCTGAGCCC AGCCGGGCCC CAGCATCCCT ACTCCCACCA GCGCCAGAAC ACAGCCCCCC GAGCTCCCCG CTAACCCAGC CCCCAGAGGG GCCCAAGTTC CCTCGTGTGA AGAACTGGGA GGTGGGGAGC ATCACCTATG ACACCCTCAG CGCCCAGGCG CAGCAGGATG GGCCCTGCAC CCCAAGACGC TGCCTGGGCT CCCTGGTATT TCCACGGAAA CTACAGGGCC GGCCCTCCCC CGGCCCCCCG 45 GCCCCTGAGC AGCTGCTGAG TCAGGCCCGG GACTTCATCA ACCAGTACTA CAGCTCCATT AAGAGGAGCG GCTCCCAGGC CCACGAACAG CGGCTTCAAG AGGTGGAAGC CGAGGTGGCA GCCACAGGCA CCTACCAGCT TAGGGAGAGC GAGCTGGTGT TCGGGGCTAA GCAGGCCTGG CGCAACGCTC CCCGCTGCGT GGGCCGGATC CAGTGGGGGA AGCTGCAGGT GTTCGATGCC CGGGACTGCA GGTCTGCACA GGAAATGTTC ACCTACATCT GCAACCACAT CAAGTATGCC ACCAACCGGG GCAACCTTCG CTCGGCCATC ACAGTGTTCC CGCAGCGCTG 50 CCCTGGCCGA GGAGACTTCC GAATCTGGAA CAGCCAGCTG GTGCGCTACG CGGGCTACCG GCAGCAGGAC GGCTCTGTGC GGGGGGACCC AGCCAACGTG GAGATCACCG AGCTCTGCAT TCAGCACGGC TGGACCCCAG GAAACGGTCG CTTCGACGTG CTGCCCCTGC TGCTGCAGGC CCCAGATGAG CCCCCAGAAC TCTTCCTTCT GCCCCCCGAG CTGGTCCTTG AGGTGCCCCT GGAGCACCCC ACGCTGGAGT GGTGCAGC CCTGGGCCTG CGCTGGTACG CCCTCCCGGC AGTGTCCAAC ATGCTGCTGG AAATTGGGGG CCTGGAGTTC CCCGCAGCCC 55 CCTTCAGTGG CTGGTACATG AGCACTGAGA TCGGCACGAG GAACCTGTGT GACCCTCACC GCTACAACAT CCTGGAGGAT GTGGCTGTCT GCATGGACCT GGATACCCGG ACCACCTCGT CCCTGTGGAA AGACAAGGCA GCAGTGGAAA TCAACGTGGC CGTGCTGCAC AGTTACCAGC TAGCCAAAGT CACCATCGTG GACCACCACG CCGCCACGGC CTCTCATG AAGCACCTGG AGAATGAGCA GAAGGCCAGG GGGGGCTGCC CTGCAGACTG GGCCTGGATC GTGCCCCCCA TCTCGGGCAG CCTCACTCCT GYTCCATC AGGAGATGGT CAACTATTTC 60 CTGTCCCCGG CCTTCCGCTA CCAGCCAGAC CCCTGGAAGG GGAGTGCCGC CAAGGGCACC GGCATCACCA GGAAGAAGAC CTTTAAAGAA GTGGCCAACG CCGTGAAGAT CTCCGCCTCG CTCATGGGCA CGGTGATGGC GAAGCGAGTG AAGGCGACAA TCCTGTATGG CTCCGAGACC GGCCGGGCCC AGAGCTACGC ACAGCAGCTG GGGAGACTCT TCCGGAAGGC TTTTGATCCC CGGGTCCTGT GTATGGATGA GTATGACGTG GTGTCCCTCG AACACGAGAC GCTGGTGCTG GTGGTAACCA GCACATTTGG GAATGGGGAT CCCCCGGAGA ATGGAGAGAG 65 CTTTGCAGCT GCCCTGATGG AGATGTCCGG CCCCTACAAC AGCTCCCCTC GGCCGGAACA GCACAAGAGT TATAAGATCC GCTTCAACAG CATCTCCTGC TCAGACCCAC TGGTGTCCTC TTGGCGGCGG AAGAGGAAGG WO 00/62736 PCT/USOO/08020 55 AGTCCAGTAA CACAGACAGT GCAGGGGCCC TGGGCACCCT CAGGTTCTGT GTGT7CGGGC TCGGCTCCCG GGCATACCCC CACTTCTGCG CCTTTGCTCG TGCCGTGGAC ACACGGCTGG AGGAACTGGG CGGGGAGCGG CTGCTGCAGC TGGGCCAGGG CGACGAGCTG TGCGGCCAGG AGGAGGCCTT CCGAGGCTGG GCCCAGGCTG CCTTCCAGGC CGCCTGTGAG ACCTTCTGTG TGGGAGAGGA TGCCAAGGCC GCCGCCCGAG ACATCTTCAG 5 CCCCAAACGG AGCTGGAAGC GCCAGAGGTA CCGGCTGAGC GCCCAGGCCG AGGGCCTGCA GTTGCTGCCA GGTCTGATCC ACGTGCACAG GCGGAAGATG TTCCAGGCTA CAATCCGCTC AGTGGAAAAC CTGCAAAGCA GCAAGTCCAC GAGGGCCACC ATCCTGGTGC GCCTGGACAC CGGAGGCCAG GAGGGGCTGC AGTACCAGCC GGGGGACCAC ATAGGTGTCT GCCCGCCCAA CCGGCCCGGC CTTGTGGAGG CGCTGCTGAG CCGCGTGGAG GACCCGCCGG CGCCCACTGA GCCCGTGGCA GTAGAGCAGC TGGAGAAGGG CAGCCCTGGT GGCCCTCCCC 10 CCGGCTGGGT GCGGGACCCC CGGCTGCCCC CGTGCACGCT GCGCCAGGCT CTCACCTTCT TCCTGGACAT CACCTCCCCA CCCAGCCCTC AGCTCTTGCG GCTGCTCAGC ACCTTGGCAG AAGAGCCCAG GGAACAGCAG GAGCTGGAGG CCCTCAGCCA GGATCCCCGA CGCTACGAGG AGTGGAAGTG GTTCCGCTGC CCCACGCTGC TGGAGGTGCT GGAGCAGTTC CCGTCGGTGG CGCTGCCTGC CCCACTGCTC CTCACCCAGC TGCCTCTGCT CCAGCCCCGG TACTACTCAG TCAGCTCGGC ACCCAGCACC CACCCAGGAG AGATCCACCT CACTGTAGCT 15 GTGCTGGCAT ACAGGACTCA GGATGGGCTG GGCCCCCTGC ACTATGGAGT CTGCTCCACG TGGCTAAGCC AGCTCAAGCC CGGAGACCCT GTGCCCTGCT TCATCCGGGG GGCTCCCTCC TTCCGGCTGC CACCCGATCC CAGCTTGCCC TGCATCCTGG TGGGTCCAGG CACTGGCATT GCCCCCTTCC GGGGATTCTG GCAGGAGCGG CTGCATGACA TTGAGAGCAA AGGGCTGCAG CCCACTCCCA TGACTTGGT GTTCGGCTGC CGATGCTCCC AACTTGACCA TCTCTACCGC GACGAGGTGC AGAACGCCCA GCAGCGCGGG GTGTTTGGCC GAGTCCTCAC 20 CGCCTTCTCC CGGGAACCTG ACAACCCCAA GACCTACGTG CAGGACATCC TGAGGACGGA GCTGGCTGCG GAGGTGCACC GCGTGCTGTG CCTCGAGCGG GGCCACATGT TTGTCTGCGG CGATGTTACC ATGGCAACCA ACGTCCTGCA GACCGTGCAG CGCATCCTGG CGACGGAGGG CGACATGGAG CTGGACGAGG CCGGCGACGT CATCGGCGTG CTGCGGGATC AGCAACGCTA CCACGAAGAC ATTTTCGGGC TCACGCTGCG CACCCAGGAG GTGACAAGCC GCATACGCAC CCAGAGCTTT TCCTTGCAGG AGCGTCAGTT GCGGGGCGCA GTGCCCTGGG 25 CGTTCGACCC TCCCGGCTCA GACACCAACA GCCCCTGAGA GCCGCCTGGC TTCCCTTCC AGTTCCGGGA GAGCGGCTGC CCGACTCAGG TCCGCCCGAC CAGGATCAGC CCCGCTCCTC CCCTCTTGAG GTGGTGCCTT CTCACATCTG TCCAGAGGCT GCAAGGATTC AGCATTATTC CTCCAGGAAG GAGCAAAACG CCTCTTTTCC CTCTCTAGGC CTGTTGCCTC GGGCCTGGGT CCGCCTTAAT CTGGAAGGCC CCTCCCAGCA GCGGTACCCC AGGGCCTACT GCCACCCGCT TCCTGTTTCT TAGTCCGAAT GTTAGATTCC TCTTGCCTCT CTCAGGAGTA 30 TCTTACCTGT AAAGTCTAAT CTCTAAATCA AGTATTTATT ATTGAAGATT TACCATAAGG GACTGTGCCA GATGTTAGGA GAACTACTAA AGTGCCTACC CCAGCTC-3' (SEQ. ID NO:3003) Human Factor Related Anti-sense Oligonucleotide 5'-CCT CCT TCC TGG TCT GTC TGC CBG BCB BBT TTG GGB BGT GBB CBG TTT TGG BBC CBT GTT TCC CBG TCT CTG BGC TGT GGC GCC CTG CTG CTC TTT CTG CT TCC CTT GGT GGG TTG GGC C GCT GGT TGT TCT 35 GGG GTT C TTG CTG CCC CTT CTG TCC C TGT TTG CTG GTG TCT GCG C CCC CBB CBG BBG BBG CBG BCB BBT TTG GGB BGT GBB CBG TTT TGG BBC CBT GTT TCC TGT GCG CTC GGC CTG GTC CCG G GGG TCT CCT CTT GTT GTT GC TTG CGC CTC CTG CTG GGG GT CC CTC TGT TCT TGT TTT GGG GGC GGG CCC GGC CGT TGT CTT G GTT TGG GGG TTT CCG TTG GGG TTC TCC TGG CCC GGG CCT TGC CC GGC CGT GGT CCC GGC TTC GTTCCT GTC TCC GTC TCG GCT CTT CTG GGG CCT TGC GCT GTC TTT GGT G GCB CCG TCC 40 BGT GBT GGT GCG GTB CTT GTC GCT GCB GCG CTC GGC CTG GTC CCG GBG BGC GCG CGG GCC GGG GGC TGC TGG G GGT TGG CCC GGG GTG CCC C GCC GCT GGG TGC CCT CGT CCT CTG CGG TC GTG TCT CCT GGC TCT GGT TCC CC GCT GCG CCC GTT GTC CTC TGG GGT GGC CTT C GCT CCC GGG TCT GGT TCT TGT GT TGG GGG TCC CTT T17 GGG CCT GTT GT GGC GTG GCT TGT GTG TTC GGT TTC TGC CCT GTC CTC CGG CGT CCC CGG BGC CTC CCC GGG GCB GGB TGB CTT TTG BGG GGG BCB CBG BTG TCT GGG CBT TGC CBG 45 GTC CTG GGB BCB GBG CCC CGB GCB GGB CCB GGB GTG CGG GCB GCG CGG GCC OGG GGC TGC TGG GBG CCB TBG CGB GGC TGB G CCT CTT TTC TGT TTT TCC C CTC TGC CTT TGT TTG GGT TCG CTT CCT TTC TGC TTC TTC C CTG TGT CTC CTG TCT CCG CTT TT TCT TC GTC TTT GTT GTT T7C TCT TCC TTG CTG BGC BBG BTB TCT BGB TTC TGG GGT GGT CTC GBT TTT BBBB GCT TGB GBB GCT GCB BBC BTT BTC CBB BGT BTB TTT GBG GCT CCB BGG BTC BCG BCC BTC TTC CCB GGC BTT TTB BGT TGC TGT CGT BBG TGB 50 GBG CTG BGB GBB BCT GTG BBG CBB TCB TGB CTT CBB GBG TTC TT7 TCB CCC GTT CT]? GGC TTC TTC TGT C CGT TGG CTT CTC GTT GTC CC TGT GGG CTT CTC GTT GTC CC CCC TTC GGG GGC TGG TGG GGC CGT CCT TGC CTG CTG G GTT CTT GGC TTC TTC TGT CCG T TGG CTT CTC GTT GTC CC TGT GGG CTT CTC GTT GTC CC CCC TTC GGG GGC TGG TGG GGC CGT CCT TGC CTG CTG G TI TCT CTT TCG CTT TCT TTT CGT CTC CTG TTC CTC CTT TT TTG CTG TTT TTT CTC CTT CTT CTC TCC TTT CTT TTC TTT TCT CTT 55 TCG CTT TCT TTT CGT CTC CTG TTC CTC CTT TT TTG CTG TTT TTT CTC CTT CTT CTC TCC TTIT CTT TTC CTC TGT CTT GTT CTG GTC CTT CGT GGG GCT CTG TGT CGC GTG G GTG CGG CCG TGG CC GGC GGB CCB GGB GTT GGB GCB GGB GCB GGB CGG GCB GGC GGC TCB TGT TTG GBT CGG CBG GBG GCB CTC CTC TGG TTG GCT TCC TTC GCC GGC BCB TGC TBG CBG GBB GBB CBG BGG GGG BBG CBG TTG GGB GGT GBG BCC CBT TBB TBG GTG TCG B TCCCTGTTTC CCCCCTTTCG TTCTGCGTT7 GCCTTTGGCG TTTTTTGTTT 60 GTTTTCTCTC TCCGTCTTTC TTCTCCCCT GTGGGBBTT CTGTGGGGBT GGCBTBCBCG TBGGCBGCTC CBBGBGCTBG CBBBCTCBBB TGCBGBBGCB TCCTCBTGGC TCTGBBBCGG TGGGAATTTC TGTGGGGBTG GCATACACGT AGGCAGCTCC AAGAGCTAGC AAACTCAAAT GCAGAAGCATC CTCATGGCTC TGAAACG GGGGGTGGCT TCCTGCCGCG TCTCTGGGCC GTCCCGTCCC TCGGCCCCGC GCCGCGCTCG GCTCCTCTCC CTCTGGCCCG GCTCGGGGCG GGGCGGGGCG GTGGGCGGGC GGCGCTGCCC TGCGCGCGGC GCTGGCCCCT 65 GCTGGCCGTC GGCTGCGCGC TGCTGGCTGC CCTGCTGGCC GCGCCGGGGC CTGTCCGCCT CTGCGGGCGC WO 00/62736 PCT/USOO/08020 56 TGTCTCCTGG CTTGTCTTCC GGCTCTTCTG CTGGGGTGGG GCTGGGCGGC CGGCCCGGTG CTGGGGCTCC TCGGGGGGGG GGGCTCTTCC GGGCTGTCTC CCTCCGGGGC GGGGGTTTCT GGCCGTGGGG GTCTTGCCTG GCCTCCGGGC TCCTGCTTGT CTTGCCTTCC TTCTCTGGTC GGTTGTGGCT CGGGGCTCCG TGGGTCCCTG GCGCCCGTTT GTGTTTTGTC TTTTCCCCTG GCGTCCCTGT GCCCCTCTCC TCTCCTTCCT CTGCTTCTCG 5 CTCTCCTTTG TGGGGCCCTC CCTGCTGCTC TTGGTTTTGG GCTTTTTTTC TCTTCCTCCT TTTTCGTGCG TGGGCCTCC GCACGCCTCT TGCCACCTCC TGCGCAGGGC AGCGCCTTGG GGCCAGCGCC GCTCCCGGCG CGGCCAGCAG GGCAGCCAGC AGCGCGCAGC CGACGGCCAG CATGCTTCCT CCTCGGCTAC CACTCCATGG TCCCGCAGAG GCGGACAGGC GCBCGCCTC TTGCCBCCTC CTGCGCBGGG CBGCGCCTTG GGGCCBGCGC CGCTCCCGGC GCGGCCBGCB GGGCBGCCBG CBGCGCGCBG CCGBCGGCCB GCBTGCTTCC TCCTCGGCTB 10 CCBCTCCBTG GTCCCGCBGB GGCGGBCBGG C GGGGTGGBBB GGTTTGGBGT BTGTCTTTBT GCBCTGBCBT CTBBGTTCTT TBGCBCTCCT TGGCBBBBCT GCBCCTTCBC BCBGBGCTGC BGBBBTCBGG BBGGCTGCCB BGBGBGCCBC GGCCBGCTTG GBBGTCBTGT TTBCBCBCBG TGBGBTGGTT CCTTCCGGGC TTGTGTGCTC TGCTGTCTCT TGGTTCCTTC CGGTGGTTTC TTCCTGGCTC TTGTCCTTTC TCTTGG CCCT TGGC CGGGBGTGGG GGTCCTGGBC GGCBCTGBBG GCBTCCBGGG CTCCCTTCCB GTCCTTCTTG TCCGCTGCCB 15 GCBCCCCTTC BTTCCBGBGG CTGBTGGCCT CCBCCBGGGB CBTGBTTBGG TBGBBBCTBG GBGGCCGGCC TCCBCCBGGG BCBTGGTCCT TCTTGTCCGC TGCCTCTCTG GGGTTTTCGG TCTGGGTGGG CTTTCCTCCT GGGGCTGCTG CTGGGCTCTT CTTTTTGTTT CTGGCCTGGT GCTCTCTCGT GCCCTTTCCC TTGGGTGTCT TGTTTTTGTG GCCTCCBCCB GGGBCBTG GTCTTTGTTr CTGGGCTCGT GCCCCBTCCC GGCTTCTCTC TGGTTCCGTC CTCTGTGGTG TTGGCCCTG CTTCCTTTTG CCTGTTGAGG GGGCAGCAGT TGGGCCCCAA 20 AGGCCCTCTC GTTCACCTTC TGGCACGGAGTT GCATCCCCATA GTCAAACTCT GTGGTCGTGT CATAGTCCTC TGTGGTGTTT GGAGTTTCCA TCCCGGCTTC TCTCTGGTTC CAAGGGAGB GGGGGCBGCB GTTGGGCCCC BBBGGCCCTC TCGTTCBCCT TCTGGCBCGG BGTTGCBTCC CCBTBGTCBB BCTCTGTGGT CGTGTCBTBG TCCTCTGTGG TGTTTGGBGT TTCCBTCCCG GCTTCTCTCT GGTTCCBBGG GB GGGCBCGGGG CBGTGGGCGG GCBBTGTBGG CBBBGCBGCB GGGTGTGGTG TCCGBGGBBT BTGGGGBGGC BGBTGCBGGB GCGCBGBGGG 25 CBGTBGCBBT GBGGBTGBCB GCGBGGCGTG CCGCGGBGBC CTTCBTGGTB CCTGTGGBGB GGCTGTCGGB GGGGGTGTGG TGTCCGCTTG GCGGTTCTTT CGGGTGTTTC TTCTCTGGGT TGGCCTGCTG CTCGTCGTGGT CGCTCCGCTC CCGGGTTCGT CTCGCTCTGT CGCCCCTTCC TTCCTTGTCG TGTTCCTCCC TTCCTTGCCT CT GBTGTTTGTT BCCBBBGCBT CBBGBBTBGC TTTGCTBTCT BBGGBTCBCB TTTBGBCBTB GGBBBBCGCT GTBGGTCBGBB BGBTGTGCTT BCCTTCBCBC BGBGCTGCBG BBBTCBGGBBGG CTGCCBBGBGBG 30 CCBCGGCCBGC TTGGBGTCBT GTTTBCBCBC BGTGBGGTGC TCCGGTGGCT TTTTGCTTGT GTGCTCTGCT GTCTCTG TTC CTTCCGGTGG TTTCTTCCTG GCTCTTGTCC TTTCTCTTGG CCCTTGGCCC CTTGBGCBGG BBGCTCTGGG GCBGGGBGCT GGCBGGGCCC BGGGGGGTGG CTTCCTGCBC TGTCCBGBGT GCBCTGTGCC BCBGCBGCBG CTGCBGGGCC BTCBGCTTCB TGGGGCTCTG GGTGGCBGGT CCBGCCBTGG GTCTGGGTGG GGCTGGGCTG CBGGCTCCGG GCGGTCCBGCCBTGGGTCTG GGGGCTGGG CTGCBGGCTC CGGGCGGGCG 35 GGTGCGGGCT GCGTGCTGGG GGCTGCCCCG CAGGCCCTGC GGTCCBGCCB TGGGTCTGGG GGCTGGGCTG CBGGCTCCGG GCGGGCGGGT GCGGGCTGCG TGCTGGGGGC TGCCCCGCAG GCCCTGC GCBCCGCCTG GBGCCCTGGG GCCCCCCTGT CTTCTTGGGG BGCGCCTCCT CGGCCBGCTC CBCGTCCCGG BTCBTGCTTT CBGTGCTCBT GGTGTCCTTT CCBGGGGBGB GBGGGGCTGG TCCTCTGCTG TCCTTGCTGG TGCTCBTGGT GTCCTTTCCG CCCTGGGGCC CCCCTGTCTT CTTGGGGCCT CTTCCCTCTG GGGGCCGTCT CTCTCCCTCT 40 CTTGCGTCTC TCTCTTTCTC TCTCTCTCTT CCCCTTTCCC GCTCTTTCTG TCTCGGTGTC TGGTTTTCTC TCTCCGCTGG CTGCCTGTCT GGCCTGCGCT CTTGGCCTGT GCTGTTCCTC CTCCGGTTCC TGTCCTCTCT GTCTGTCGCC CCCTCTGGGG TCTCCCTCTG GGTGGTGGTC TTGTTGCTTG GGCTGGGCTC CGTGTCTCCB GTGCTCBTGG TGTCCGCTGB GGGBGCGTCT GCTGGCGCTG GTCCTCTGCTGTC CTTGCTGGTG CTCBTGGTGT CCTTTCCGCC CTGGGGCCCC CCTGTCTTCT TGGGGCCTCT TCCCTCTGGG GGCCGTCTC TCTCCCTCTC 45 TTGCGTCTCT CTC'TTCTCT CTCTCTCTTC CCCT'TTCCCG CTCTTTCTGT CTCGGTGTCT GGTTTTCTCT CTCCGCTGGC TGCCTGTCTG GCCTGCGCTC TTGGCCTGTG CTGTTCCTCC TCCGGTTCCT GTCCTCTCTG TCTGTCGCCC CCTCTGGGGT CTCCCTCTGG CGTGGTGGTC TTGTTGCTTG GGCTGGGCTC CGTGTCTCCB GTGCTCBTGG TGTCCGCTGB GGGBGCGTCT GCTGGC CTGCTGBGGC TTGGGTCTCC GGGCGBTTCT CTGCBGBBGB TGCTCBBBGG GCTCCGGCBG TTCCTCCTTG BTCTGGTCGCT GTCGTBCCBG TCGGBCCBGT 50 BBTTCBGBTC BTCBTTGGCT CCTBTTTCTT CTGCBBBCBG CTGBGTGGBG BCBBGBBBBB BGBCTGCCBB GGCCBCGBGG BTTTTCBTGT TGGBTTTTGC GBCGGBCBGT CCCGCGGGGT GCTGAGTTTC TCTGGTTCCT CCGBGCGCBC GTGGTCGCTC CGCGTTTCTC TGGTTCCTCC GGTCCCGCGG GGTGCTGTCT GGTCGCTGTC GTGGCTTGGG TCTCCGGGCG GTTTCCTTCC TTTTCCGC CGGCCCTTCT CACTGGAGGC ACCGGGCAGT CCTCCATGGG AGGGTTGGGC TTGGCCGGGG CTGCCCGGTG CCTCCTCTTG GCTGGTCCCT CGTTGTCCTT 55 GGGCCCCGC TCCCGCTGCT CGGCCTCCGT GTTCTTTGGC CTCTTGCTCC GCCTGCTGTC TTGTCCCGTC CCCTCCTCGC TTGCGTTTCC CTCTTCCTTG TCTTCCAGGC CTTCCTCCGC TTCCGCTGCT GGGGCCCGCG CCGGGGGGGC GCTCGGCTCC GCGGCTTCCT CCCCGGCTGG GGGGTCCTGG TCTCCGGGGC CTGCGGCTCG CGGGCTCGGG GCTGCGTGCG CCGCGCGCGG CGTCCGCGGT GGGTGGCGCT GTCCCGCCGT GGTGTGTCTC CGTTCTCGTC CTGCGCCGTC CTGGTCTGCC CGTGGGGTCC TGGGCGTGGT GGGGGGCGTC TGGTGCCTCG 60 TCTGCCCCGT GGGGCTTCGG GCTCGGGGCT GTTCGTCCCC CCTGCCGCTC TGTGGCCTCC GGGGCTCCTC GTTTTCGCTG CTTCGGGTGT CCTTCTCGGC GTGTGGCCCC GGGTCCCGGC CCTGCTGGGC TGGGCGGGGT CGCTGCCCTG GGCTTCTGGC CCGTCTGGTT GTCTGTCGGT GCTTGTCTCG GGTTTCTGGC CTCTGTGCTG GGCGCTTCTC TGCCTCCTGC TCCGCCCTCC TGGTGGCTCG GCTGGGGGTG CCCGTGCGGG GGTGGGTGTG GGGTGTTTTC GGGGTCCTCC CCTTCCC GTT TCA TCT TGG CTT TAT CCTCT CCC CTT GTT CCT CCC CTCT 65 CCT GCT CTG GRG TCT CCT C TTC CCT CCC TCC CCT GCC GTG TTG TCT GTG GGT GTC GTT TCG CTC TTG TTG CCC TGG GCC CTT CCC TGC TGG GGG GGA GTT TCA TCT TGG GTT TCB TCT TGG CTT TBT CCTCT CCC WO 00/62736 PCT/US00/08020 57 CTT GTT CCT CCC CTCT CCT GCT CTG GRG TCT CCT C 'ITC CCT CCC TCC CCT GCC GTG TTG TCT GTG GGT GTC G'rT TCG CTC TTG TTG CCC TGG GCC C'rr CCC TGC TGG GGG GGB G'117 TCB TCT TOG GGG GGB GTT TCB TCT TGG CiT T CCGTGTTGTC BGTGGTGCTG CCCGTTTGBG GTBTGGCGCT CCBCCBBTTC CCTTTTCTCC TTGTTTTCCG TTTCTCTTGC CGTCTGTGGT T GCTCAGCCTC CAAAGGAGCC AGCCTCTCCC 5 CAGTTCCTGA AATCCTGAGT G'ITGCCTGCC AGTCGCCATG AGAAC'ITCCT ACCTTCTGCT G'TTACTCTC TGCTTACTTT TGTCTGAGAT GGCCTCAGGT GGTAAC'=C TCACAGGCCT TGGCCACAGA TCTGATCATT ACAAT'rGCGT CAGCAGTGGA GGGCAATGTC TCTATTCTGC CTGCCCGATC 'FfrACCAAAA 317CAAGGCAC CTGTTACAGA GGGAAGGCCA AGTGCTGCAA GTGAGCTGGG AGTGACCAGA AGAAATGACG CAGAAGTGAA ATGAACTTr TATAAGCATT CTI=AATAA AGGAAAATTG C=~GAAGT AT ATCC TI7AAG TCAATGGACT 10 TI7GCATCAGT CACACCATCT TTrGTTACTT TGGACTCCC CAGCTATGTr CAATAATTAC TGTrCTrCCC TTGGGCCCCA TrGTAATGGC TACAGCCTCG ACAAAAAGTC TACACTrFGA AGCATTAAGG CTCGGACATC AGCACCAAAT TTfACATC'IT TACCATCACT TCAAGTGAGG TGAGGAGCCA GTAGCCTGGA CACTGGTCTC ATCTGGTGAA AGACTGTGG TAATGGAAGC A M CTGTGG GGTGCTGGCA GGACATGTGC ATGGCGAGGC AGGTCATCAG CAGCAAGTGA GAGCTGCCTC TTACTITCTA AAGGTGACAT AGCAAATATA CAAAAAAAAA 15 TAAATAAATT ATI'AAYIAG GTAGAGCACA TAAAGGCTr A'ITTCATAT CCAYI1CTCT GTATGC'ITTC TrCACCAGGA AGAAATAGTT 'TAGTGTCAG GAATGAATGA GTCTGCCCCT CAATTCCAGC CTGCTCAACA CACAAGGAAA CAAAGCCCTG ACAATCAGAG TGACTCCCTG GTGACTAAGC TCCCAGTCCT GGATGCATAT 'FrGTTTAGCA GTFCTGACAG CAYI1?GACCC AGCCCTCTCT CTGCATATCC CATCAGAACC TTCTTf iTrTTTTC'1 TGAGACTGAG TCTTGCTCTG TCGGAAGCGA CTCCTGTGCC TCAGCCTCCC AAATACCTGG 20 AATTATAGGC GTAAGCCATC ATGCCTGGCT AATITIGTA TI=fCATGG AGATGGGGTT TTGCCATGTT GGTCAAA'I17G GTCTCACACT CCTGACCTCA TGTGATCCAC CTGCCTCAGC CTCCCAAACT GCTGGGATGA CAGGTGTAAG CCACCATGCT AGGCTCAGAA AiTCC'In ATAAAAATGT CATTAAGGAT CTTGGCTGCA CAATATCGTT ACCAGCTTCC TAAATCCA C'ITCTGGCCT GCCAGGAATC AGGTrCTI1CA GAACCTGACA T=rAAATGA AGAGGTCAGG CAGTTCATGA GGAAAGCCTC ATrGTCCCCA TGTCTCTGTC ACTGCTGCAC 25 CCCTGAGACA TCACAGACAT GGACACTGGG GCCTGCI1GT TrCTCAAACT GCCCTTAGAT CGAAAGAGGG AGGAACCAGG ATGAATGCCA CTCATTfCC CAAGAAAGGC CCTCTCCTGA GTGCCCGGGA TGGGGCTCTG TCCATTGCCT GGGGCCGCCA ATFGCTACTC TGGG'FFACGG AGGAAGGACA GGGTCCTGAG AGACACCAGA GACCTCACAC AGCCCTGAAA ACATGGGGCT CC317CATAAG TG'I=rCCCAT CACCAACAGG GAGACCACGT GGAGGCCTTG CAGCCCCACT CGGTGCTTCT CCACCAAATC CCAAGGGCAG TGACGCTGAC GTCTGTGGAA 30 AGCAGAGAAA GCCCTGGCTC CCAAAGCCCT GAAGTCCCTG TGGAGCTGAC ATTCCCTGAG TGACGGTGTG AATGGAAGGA ACTCAAGTGC GGGTGGTAGG CCACCTCCTG GCCCAGGCCT GGGTGAACTC TGAGGGGACA CATGTAGTCA CAATCCCATC CTCCCA'ITCT CCTTCTCAGA GGAAGGAAGT GGGCATCCAT CTGCCTCATC TCTCTCCCGT GGGGAAGATG GGGAGYI17CA GGGGAACTT CACATAAATT TCACCAGCTC AGATCTCCTG TGAGGATGGG GCCCACCATG CTCCCGGTGC TGCCAGAGGC CCTGAGCCCC TCCCAGGGTC CCTGGGTTTG 35 AGCCAGCCCT GTATCATCCC CAGGAGCTGA ATGTCAGAGC AATGGATAGA AT7AGATGGA AAGAGCTCTC AATI17GACCT GAGACTGTCC CCAGATACTC AGGAAAAACA GGACGTCGCA CAGAGTGGGC AGCAGGTGAG TGGCAGGT11A TAGGTCCTGA GTTTGAGTL'T GTrCTCACGT GAGACAGACC CAGCCCCTCA CTCCATTCAC ACACTGGGT11 'ITAAATGGTG CAAGATAGGA GCAATITCT GGTCCCAAGA GCAGGAGGAA GGGA'IrTCT GGGGTrCCT GAGTCCAGAT TrGCATAAGA TCTCCTGAGT GTGCATTGTT CT[ITGAGGAC CATITCTCTGA 40 CTCACCAGGT AAGTGGCTGA ATTCTAACCT CTGTAATGAG CATTGCACCC AATACCAG'Fr CTGAACTCTA CCTGGTGACC AGGGACCAGG ACCTI17ATAA GGTGGAAGGC TTGATGTCCT CCCCAGACTC AGCTCCTGGT GAAGCTCCCA GCCATCAGCC ATGAGGGTCT TGTATCTCCT CTI1CTCGTrC CTCTTCATAT TCCTGATGCC TCTFCCAGGT GAGATGGGCC AGGGAAATAG GAGGGTTGGC CAAATGGAAG AATGGCGTAG AAGTTCTCTG TCTCCTCTCA TTCCCCTCCA CCTATCTCTC CCTCATCCCT CTCTCTCCTT CCTCTCTCTG TGTGTCCCCT 45 CCATCC1T117 CTCCTGCTTC TCTCTCTTrCT TCCCTCTCTC TCTTITCT GTCTTTC'IIr TTCCTCTCTC CCTAGAGCAT GT=CTTTI~ CTTTCTCT17 CCTTTCTrCT ACCCACACTT TTAGACTGAA TGCCCTATr AA'ITGAACAA AGCATTGCTT1 CCTTCAATAG AAAAGGAGTT TGAGAACCCA ATGGACACCT CACTCGTTCT TCTAAGCCAA TATGAAGGAG CCCAGTAGCT TGTAAATATC ATCTCTTCAC TGC'TrTCCAT GCTACAACTG CTGAGACTAT GGYI'GAAACC TGTrAGGTGA CTFT7AAAT AAAAGGCAGA AATITTGATf TI'ATCTAAAG 50 AAAGTAGTAT AGAATGTCAT ITTrCTAAATT ITTATA TTTA AAGGGTAGAT ACTGCAACCT AGAGAATTCC AGATAATCTT AAGGCCCAGC CTATACTGTG AGAACTACTG CAGCAAGACA CTCTGCCTCC AGGACYIJC TGATCAGAGG CCCTGAGAAC AGTCCCTGCC ACTAGGCCAC TGCAGG I1CA CAGGACAGGG TACAGCCCAT TGAAACCTAC 'ITAAACCT GGATGCCTAA CCTTCATTL CTCC'I17GATA TTATGAAAAT AAAATAAAAA CCATGAAAGG ATAAAAGAGG GAGAGTGGAA GGGAAGGATG GAGAAAGGGA AAAAGAAAAT ITGAGAGTAA 55 ATCCTAAAAC AATTAATCTA ATAGATATCA TCTTGTGAAA TCCTCATF ACCAATCTTA TITATGAGTC CTGGGTITG TGAGAACAAT GGGGTrCTGA GAGGCACCAG AGACCTCATG TIT7CCAAAA CCTAGAACAG TATAATGAAG GAAGGCGGGG AGGCAGGGAG GCAGGGAGGC AGGGAGGCAG GGAGGCGGGC AGGTGGGGAG GGAGGGACGG AAGGAGGGAG GGAGGGAGGG AGGGAGGGAG GGAGGGATAA AAAAAGAAGA ATGAGGTTGA AACCAGGACT TAGATATTAG AAACAAGCCA TTIACAAAATT TAITTFCTATG GTTAATTGTG G TITCAACT 60 GTAAGTTACT TGGTGTTrAAT TT1CCTATTAA ACAATT17CAG TAAG'ITGCAT CTT'TTATCC CATCTCAGGT CAAATAC'ITA ACAGACTAAA TGATTGAAA AAGCAAAAGT TrACTGGC FT GTGTGTGTTA AAATGGAGGT ATGGTGGC'r TGATATFATC TTCTTGTGGT GGAGCTGAAT TCACAAGAGA TCGTTrGCTGA GCTCCTACCA GACCCCACCT GGAGGCCCCA GTCACTCAGG AGAGATCAGG GTC=TCACA ATCAGGTI7CT ACAAAAATAA ACATCCCCCC AACCACAGCA GTGCCAG3Tf CCATGTCAGA AAC'ITAGATC CAAATGACTG ACTCGCGTCT 65 CATTATCATG ATGGAAAAGC CCAGGCTTGA GAAAGAAGCC CGCTGCGGAT '1TACTCAAGG CGATACTGAC ACAGGGTTTG TGTTITTTCCA ACATGAG TF TGAGTTCTTA CACGCTG'rfr GCTCTTTG TGTGTTrr WO 00/62736 PCT/USOO/08020 58 CCCTGTTAGG TGTITGGT GGTATAGGCG ATCCTGTTAC CTGCCTTAAG AGTGGAGCCA TATGTCATCC AGTCTTTTGC CCTAGAAGGT ATAAACAAAT TGGCACCTGT GGTCTCCCTG GAACAAAATG CTGCAAAAAG CCATGAGGAG GCCAAGAAGC TGCTGTGGCT GATGCGGATT CAGAAAGGGC TCCCTCATCA GAGACGTGCG ACATGTAAAC CAAATTAAAC TATGGTGTCC AAAGATACGC AATCTTTATC CTAGTAATTG TGGTCATTGG 5 GTGATGTT7GG TTTGGGCAGG CCATCTCTAA TATCCTTGAA ACACCTTr CTGCTCTCCA GGAAGGGGTC AGGGCTGCCA CAGCGGGGCT TGGAGTGCTT TCCAGGGTCA CAGGCATCTG TATTCTTTGG ATTCCTTGAC CTTCCCCAT TATTCCCGGC ATTTTCCTAA AACGTGTGCT TTGCTCCTCC TGCATCCTCC CCTTGCATGC CCTCACCTAC CCCACATCTT CCCTAAAAAA AGCAAGCCCA ACTCAAAGAC CAGTTCCCTC ATGGAATCAT AGTGGATCTG CCAAGGGAGG GGATGCCCAG TCCTCTGTTC TTCACAAGAC TCCCTTCTTC TGGCTAAGGT 10 TTCTTATGCA ATTAT CTGCAGTGGT AAAAAGATTC TATATCTGCT GTTTGATGAA TGCAGCACCC ACTAGCCACA TAGTGCTCGT GAGCACTTGC AATGCGGCTA GGGTGATTrC AATTAACCTA AAAGAGAACA GCCACAGGGA GCATGTGGCT GCCATATTGG ATGGTGCTGC TTTGAGAACA AAATGAGAGA AATGAAGCCT CTATTACCT TGGTTGGCGG AACACATTGA AGGGACTCTG TATTGATACC AGGCTTCAAA CTTTGGGAAG TGTACTGGCC AACTTAAACA CATCCACAGG AGAATGAAGA GGTGGGAA GGGACCAGAA ACCAGGCATT 15 GAGGACAATG AGAAGAGTTT TTCAAAAGTG GAATTACTGC AAAAAGTGGA AAAATAGCCT TTGGATGGAA GTTACTGATG AGACAATTTC CATCGGTGTG AAAGCCATCT TTCCAACAGA GATCTGCAAC ATGAGAATGT ACTGTCTCCT AGGGTAGCGA TGGCCTCTTG TATTAGTCCG CTCAGGCTAC CAGATTTATC GTTTAAACTG CCCATAAACA GACCAGGCAG TTTAAACAAC AGAAATTTAT TTCCTCGCAG TCCTGGAGGC AGGAAGTCTG CGATCAAGGT GGAAGCAGGG TTGGCTTCTTr CTCAGGTGTC TGTCCTTGGC TGGTAGATGA CCGCCGCCTC 20 CCTGGGTCCT CACATGGTCT TTCCTCTGTG TGTGTCTGTC CCAATCTCTT CTTATAAGGA TGCAAGTCTT ATGGATCAGA GCACACCCCA ATGACCGTGT TTAACTTGAA TCACCTCTTT AAAGTTTCTC TCTCCAAATA CAATCACCTC CTGAGGCACT GT7AGGGCTT CGACACAGGA ATTCTTTTCC TAGGGGATTC AGTTCAGTCC AAAACGCCTA CCAGTGGAGA CTTGCAACAT GGCGGCCTGC TGGTCCCTCG CCAGGAATAT CACAGGCGAC TGTTCCCTGT TGCATGGAAT AGAAGGCTAT TCCAGAGTAC TGTCTCTATT TATCAGATCT GGGATACTGG 25 GAGAAGGGCA AAATAAAGTC CAAGTAGAAA AAAAAACTAT GAAAGTTA GAGAGTAACC ATAATTTCAG CCCGATGTGA AACGATCCTA GATCAGCT GAAATAGTGA TGTGGGAAGT GAGGGGGCCG GGATTCAAGG CAGAGGGAAC AGCGTAACTG AAGGCATGGA AGGAGGGAAG TGTAGGCTGT GTTTGAAGAG TGGCAGCTGC TTCCACATTT CTAAAACACA GGATGTGATT TTGGGGTGTG TTGAGACAAG GCAGAAAACT TGTTTGGAAA AATAACTTGA ATTCCCTGCA CATTTAAAAT CTCTCAGCAG AAGAAAACCC CACTCAGAAC CCCACTGTTC 30 ATTCCTTGGC TTGTATTTGG SCACAGCTGG CATAGCCCCA GACTGAGTAA GCTCTTCAGA CACCTCATTT CATGAGTAGC CCCAAAGATC AATCATGGGC CAATCTrG GAAGAGAAGA CTCTCCGGTG TTTTGCAGTT ATTTGTTCTG CTTTrCGCGAG ATGTTCTCAA ATCGTTGCAG CTACAAGCCA TGAGTCTGAA GTGTTTGTGT TCCCTCCTTA CAGGTGGTAA CTTTCTCACA GGCCTTGGCC ACAGATCTGA TCATTACAAT TGCGTCAGCA GTGGAGGGCA ATGTCTCTAT TCTGCCTGCC CGATCTAC CAAAATTCAA GGCACCTGTT ACAGAGGGAA 35 GGCCAAGTGC TGCAAGTGAG CTGAGAGTGA CCAGAAGAAA TGACGCAGAA GTGAAATGAA CTTTTTATAA GCATTCTT AATAAAGGAA AATTGCTT GAAGTATACC TCCTTTGGGC CAAAATGAAT CTTGTGTCTC AATTGGAAGA GGTAAAGAAG TAGGGGGTTA GGGTGCATGG GTTGGAACGT GAGACAGGTC GAACCACAAA GCCTGCCTGG AAAAGGGGAG TGACGTCCTA GGCTTCAGTG ATGTCACCTC CACTTTGTTT GATCCACAAA CCAACAGGTG ACTGATTTTG GTCAGCTCAG CCTCCAAAGG AGCCAGCCTC TCCCCAGTTC CTGAAATCCT 40 GAGTGTTGCC TGCCAGTCGC CATGAGAACT TCCTACCTTC TGCTGTTTAC TCTCTGCTTA CYTTGTCTG AGATGGCCTC AGGTGGTAAC TTTCTCACAG GCCTTGGCCA CAGATCTGAT CATTACAATT GCGTCAGCAG TGGAGGGCAA TGTCTCTATT CTGCCTGCCC GATCITACC AAAATTCAAG GCACCTGTTA CAGAGGGAAG GCCAAGTGCT GCAAGTGAGC TGGGAGTGAC CAGAAGAAAT GACGCAGAAG TGAAATGAAC TT GAATTCACAT TTCTCACCTT TTGATGTATT AAGAAAGTAT GGAGAAATAT ATCCTCTATC AAATTTTCAT 45 GCCTTCAATA ATTTCTAATT CATCAGTCAG TGTTTCCA TCCTTTACTG TGATGATGCC CTTTCTTCCA AACTTTCA TTGCATCAGA GATGATGTTA CCAATTTCT7 TGTCTCCATT TGCAGAAATT GTAGCAACCT GTGCAATTTC TTCAGGTTTG GTCACAGGTT TAGACTGCTT TTAAGTTCA GCAATTACAG CATCAACAGC TAACATCACA CCTCTCTTGA TTTCCACTGG ATTAGCACCT TTGCTAACCT TCTGGAAGGC TTATTTGGAA ATAGAGCATA CCAGTACAGC AGCAGTGATA GTGCCATCCC CCAGTCTCTC CATTTGTGTT ATTGGCAACA 50 TCTTGGACAA GTTTAGCTCC AATGCTTTTA TATTTATCCT TTAAGTCAAT TGACTTTGCA TCAGTCACAC CATCTTTTGT TACTTTGGGA CT7CCCCAGC TATGTTCAAT AATTACTGTT CTTCCCTTTG GCCCCATTGT AATGGCTACA GCATCGACAA AAAGTCTACA CTTTGAAGCA TTAAGGCTCA GACATCAGCA CCAAATTTTA CATCTTTACC ATCACTTCAA GTGAGGTGAG GAGCCAGTAG CCTGGACACT GGTCTCATCT GGTGAAAGAC TGTGGGTAAT GGAAGCATTT CTGTGGGGTG GTGGCAGGAC ATGTGCATGG TGAGGCAGGT CATCAGCAGC 55 AAGTGAGAGC TGCCTCTTAC TTTCTAAAGG TGACATAGCA AGTATACAAA AAAAAATAAA ATATTAATTT AGGCAGAGCA CATAAAGGCT TTATTTCATA TTCCATTTCT CTGTATGCTT TCTTCACCAG GAAGAAATAG TTTTAGTGTC AGGAATGAAT GAGTCTGCCC CTCAATTCCA GCCTGCTCAG CACACAAGGA AACAAAGCCC TGACAATCAG AGTGACTCCC TGGTGACTAA GCTCCAGTCC TGGATGCATA TTTGTTAGC AGTTCTGACA GCATCTGACC CAGCCCTCTC TTGCATACC CCACCAGAAC CTTCTTTTTT 7TTTTTTTTC TTTGAGACTG 60 AGTCTTGCTC TGTCGGAAGC GATT1CCCGTG CCTCAGCCTC CCAAATACCT GGAATTATAG GCGTAAGCCA TCATGCCTGG CTAATTTTTG TATTCAT GGAGATGGGG TTTTGCCATG TTGGTCAAAT TGGTCTCACA CTCCTGACCT CATGTGATCC ACCTGCCTCA GCCTCCCAAA GTGCTGGGAT GACAGGTGTA AGCCACCATG CTAGGCTCAG AAATTCCTT TTATAAAAAT GTCATTAAGG ATCTTGGCTG CACAATATCG TTACCAGCTT CCTTTAAATC CACCTCTGGC CTGCCAGGAA TCAGGGTTCT TCAGAACCTG ACATTTTAAA TGAAGAGGTC 65 AGGCAGGTCA TGAGGAAAGC CTCATTrGTCC CCATGTCTCT GTCACTGCTG CACCCCTGAG ACATCACAGA CATGGACACT GGGGCCTGCT TGTTTCTCAA ACTGCCCTTA GATCGAAAGA GGGAGGAACC AGGATGAATG WO 00/62736 PCT/US00/08020 59 CCACTCATr TCCCAAGAAA GGCCCTCTCC TGAGTGCCCG GGATGGGGCT CTGTCCATTG CCTGGGGCCG CCAATTGCTA CTCTGGGTTA CGGAAGAAGG ACAGGGTCCT GAGAGACACC AGAGACCTCA CACAGCCCTG AAAACATGGG GCTCCTTCAT AAGTGTTTCC CATCACCAAC AGGGAGACCA CGTGGAGGCC TJ'GCAGCCCT ACTCGGTGCT TCTCCACCAA ATCCCAAGGG CAGTGACGCT GACGTCTGTG GAAAGCAGAG AAAGCCCTGG 5 CTCCCAAAGC CCTGAAGTCC TGTGGAGCTG ACATTCCCTG AGTGACGGTG TGAATGGAAG GAACTCAAGT GCGGGTGGTA GGCCACCTCC TGGCCCAGGC CTGGGTGAAC TCTGAGGGGA CACATGTAGT CACAATCCCA TCCTCCCATT CTCCTrCTCA GAGGAAGGAA GTGGGCATCC ATCTGCCTCA TCTCTCTCCC GTGGGGAAGA TGGGGAGTTT CAGGGGAACT TTCACATAAA TITCACCAGC TCAGATCTCC TGTGAGGATG GGGCCCACCA TGCTCCCGGT GCTGCCAGAG GCCCTGAGCC CCTCCAGGGT CCCTGGG'TT GAGCCAGCCC TGTATCATCC 10 CCAGGAGCTG AATGTCCGAA CAATGGATAG AATT1AGATGG AAAGAGCTCT CAAYTTGGCC TGAGACTGTC CCCAGATACT CAGGAAAAAC AGGACGTCGC ACAGAGTGGG CAGCAGGTGA GTGGCAGGTT ATAGGTCCTG AG'TTGAG'T TGTTCTCACG TGAGACAGAC CCAGCCCCTC ACTCCATrCA CACACTGGGT TTrAAATGGT GCAAGATAGG AGGAATTC TGGTCCCAAG AGCAGGAGGA AGGGAYIIC TGGGGTTTCC TGAGTCCAGA ITTGCATAAG ATCTCCTGAG TGTGCATrGT TC'ITrGAGGA CCATTCTCTG ACTCACCAGG TAAGTGGCTG 15 AATTCTAACC TCTGTAATGA GCATI7GCACC CAATACCAGT TCTGAACTCT ACCTGGTGAC CAGGGACCAG GACC ITATA AGGTGGAAGG CTT1GATGTCC TCCCCAGACT CAGCTCCTGG TGAAGCTCCC AGCCATCAGC CATGAGGGTC TTGTATCTCC TC31?CTCGTT CCTCITFCATA TTCCTGATGC CTCT~rCCAGG TGAGATGGGC CAGGGAAATA GGAGGGTTGG CCAAATGGAA GAATGGCGTA GAAGTTCTCT GTCTCCTCTC A'ITCCCCTCC ACCTATCTCT CCCTCATCCC TCTCTCTCCT TCCTCTCTCT GTGTGTCCCC TCCATCC'lM TCTCCTGCT 20 CTCTCTCTTC TTCCCTCTCT CTC TTI'T CTGTCMTCT 1TICCTCTC TCCCTAGAGC ATGTCT-rCT TTCTTTCTCT TrCC'TrCTr CTACCCACAC YTTAGACTG AGTAGACTGA ATGCCCTATT1 TAATTGAACC AAGCATFGCT TCCTrCAATA GAAAAGGAGT TTGAGAACCC AATGGACAAC TCACTCGTrC YTCTAAGCCA ATATGAAGGA GCCCAGTAGT TTGTAAATAT CATCTCTTCA CTGCTITCCA TGCTACAACT GCTGAGACTA TGG'I1GAAAC CTGTTAGGTG ACTTMAAA TAAAAGGCAG AAA T=GAT 'TTTATCTAAA GAAAGTAGTA 25 TAGAATGTCA ITICTAAAT TFFI'ATA'TrT AAAGAGTAGA TACTGCAACC TAGAGAATTC CAGATAATCT TAAGGCCCAG CCTATACTGT GAGAACTACT GCAGCAGACA CTCTGCCCCC AGGACTI=C TGATCAGAGG CCCTGAGAAC AGTCCCTGCC ACTAGGCCAC TGCAGGTTCA CAGGACAGGG ACAGCCCAT7 GAAACCAACT YI1AAACCTG GATGCCTAAC CTTCATITC TCCTTGATAT TATGAAAATA AAATAAAAAC CATGAAAGGA TAAAAGAGGG AGAGTGGAAG GGAAGGATGG AGAAAGGGAA AAAGAAAATT TGAGAGTAAA TCCTAAAACA 30 ATTAATCTAA TAGATATCAT CTT1GTGAAAT CCTCA T=A CCAATCTTAT TT1ATGAGTCC TGGGTFTTGT GAGAACAATG GGGT1'CTGAG AGGCACCAGA GACCTCATAT TrCCAAAAC CTAGAACAGT ATAATGAAGG AAGGAGGGAA GGAGGGAGGG AGGGAGGGAA GGAGGGAAGG AGGGAGGGAG GGAGGGAAAC AAAAAGAAGA ATGAGGTTGA AACCAGGACT TAGATAT1'AG AAACAAGCCA T7ACAAAATT TA'ITTCTATG GTrAATTGTG GT1TCAACT GTAAGTTACT TGGTGTTAAT TTCCTATFAA ACAA'ITTCAG TAAGTTGCAT 35 CYTITTTATC CCATCTCAGA TCAAATACTr AACAGACTAA ATGATTTGAA AAAGCAAAAG V[TACTGGCT TGTGTGTGTT AAAATGGAGG TATGGTGGCT 'ITGATAT7AT CTTCTTGTGG TGGAGCTGAA TJTCACAAGAG ATCGTGCTG AGCTCCTGCC AGACCCCACC TGGAGGCCCC AGTCACTCAG GAGAGATCAG GGTCTrTCAC AATCAGGTTC TACAAAAATA AACATCCCCC AAACCACAGC AGTGCCAGTT TCCATGTCAG AAACTTAGAT CCAAATGACT GACTCGCGTC TCATFATCAT GATGGAAAAG CCCAGGCTFG AGAAAGAAGC CCGCTGCGGA 40 PIACTCAAG GCGATACTGA CACAGGGrT GTG TTCC AACATGAGTT1 'rrGAGTTCTr ACACGCTGTT TGCTC'T= GTGTGT=T TCCCTG'ITAG GTGTT=GG TGGTATAGGC GATCCTGTTA CCTGCCTVAA GAGTGGAGCC ATATGTCATC CAGTCTTG CCCTAGAAGG TATAAACAAA FTGGCACCTG TGGTCTCCCT GGAACAAAAT GCTGCAAAAA GCCATGAGGA GGCCAAGAAG CTGCTGTGGC TGATGCGGAT TCAGAAAGGG CTCCCTCATC AGAGACGTGC GACATGTAAA CCAAATTAAA CTATGGTGTC CAAAGATACG CAATCTTTAT 45 CCTAGTAATT GTGGTCATT1G GGTGATGTTG GTT-TGGGCAG GCCATCTCTA ATATCCTTGA AACACCTITTT TCTGCTCTCC AGGAAGGGGT CAGGGCTGCC ACAGCGGGGC TTGGAGTGC GAA'ITCCCTG TAAGCCCTGT TACAGGGGCT GCACCCCAGA TACAACCTGA CCTGTGTCCA AGGCGGGCAA CTCAACCCTT AGATATTGAA TGGGTCCCAT GGCACCAATG CTTAAACACC AGCAGCCCTC ACAACCACAG ATCGTG1TI AAGGATGAGG AGGTAG'1CT CTGGATGCAC AGGCTTCAAT CCAAATGGGC TCATGACGCC GCAGCACACA CCCAGTCTGC 50 AGCCTGAAGA GTTGGAGCAT TGCATTCACA GAAAGCATCC AGACATGATC ATGGGCTCAG GGATACACCT GTTCTCCGAT GTGTACCAGT GAAGGATGGA AACTCCTATG CCTCCCAGAA AGCACCACTC AAGCTTTTGC TGAATGCTTC TCTGAAGGCC CACAAGGCTG AGAGGCTGTG CAACACCAGC AGTAAAGTGA ATGCCCAGAC TCCCACCTCC 'ITTCTTGGGT GGCCATCTGG AAAGGCCACT CCCACCCTGA TGGCTAATGC CTCAGACCAG TTCF'rGGCCC AGATGATCCT AGACAATTGT TTAAGCTAA ACTG'flCA'IT GGCCAAGCAA ACAGGTGATA 55 GTACCTCTGG GGAACCACAT GCCGCGTGTA CATCCAGATC TCAGGAGAAC CCAAAAATGT CTGYTCCACA TAGCAACAGA AGCCCAGGTA GCACTCAGTC TCACCTGGGT GTTCTCCAAC ATCCCAGCTC AGCCAAATGG C'TrTCATTAG TT MATGGT TAGACCCCAG GTCCTCGGGA CACTGC ITA GAAACACATT CCAAATCCTC CTCTGTGTGC AGGTGGCATT1 CCTATCCCAA TCTC'TrGCA GGGCGTATAC TGTGATACGC AGCCAGGCTG TCCCAGAGGC CTrAAATATT CCCT1FGGTGC AGGTAG'I1CA GCTTAGCCAC AGCCAATGCA TCACAGGGTC 60 AACTGTGTTA GGAGCCATTG AGAATCCATA GTTGGT'FGCT GCCTGGGCCT GGCCAGGGCT GACCAAGGTA GATGAGAGGT TCCTCTGTGG AGTTCTACTT TAACCTCACC TrCCCACCAA ATI17CtCAAC TGTCCTTGCC ACCACAATTA MPAATGGAC CCAACAGAAA GTAACCCCGG AAATTAGGAC ACCTCATCCC AAAAGACCTI' TAAATAGGGG AAGTCCACTT GTGCACGGCT GCTCC'I1GCT ATAGAAGACC TGGGACAGAG GACTGCTGTC TGCCCTCTCT GGTCACCCTG CCTAGCTAGA GGATCTGTAA GTACTACAAA ACTI1AAAC17 TACACTGAGT 65 TI1?CATCATT GAAGCTATGC CTCCAATCTG ACCTCTGACT GTGGGGCCGC CCCAGAGGGA CCCAGCGGGT GAATCCCTGC TAGGAACGTC TGTCCGGACC TCTGGTGACT GCTGGGGACG ATGGCTTCCA GCTAACTI7AA WO 00/62736 PCT/USOO/08020 60 TAGAGAAACT CAAGCAGT[ CCTTCTAAAT ACACATGTCA CATGTCCTGG TTGACATGTC CAGTAAGAAG ACTATCACAG GTC'=GGAA CA'ITIT G AGAGAAACCT ATrAGGTCC TTGGTCTGTr ITT7CAATCAG GTTGTffGAT TFIGCTATT GAGTTG'FrGG AATTCCTTAT GTATrCAGAT ATTTGCCCCT TCTGCCATGT AGGTITTGCA AATAT1TCT CTCATTTCT GGGTrATCTr TTCACTCGGT TGATrG'IMC C'1TTGCTGTG 5 CAGATGC'Tr AGCGTTAAAT GAAGCCACAC TTGTCTAMI TCCCTITAT TGCCTGTGCC TTTGGTGTCA TAGCCAAGAA ATCATTACCT ACATCAATGT CAAAAGCTTT ATCCTTCTAT ACACTTCTAG TAG1TT-ATGG YPCAGTTGT TACATTTAGG TnI7CAA'ITC ATTCTGAGiTT GATGTTCGTA CATGGTGTGA GATAAAGATT TAAATACATA CATATATAAA ATCATGAGGT AGTGTACACT ATAAATATAC AATIGTTAAT TG'ITACTCAA GTCTAAGTAG AGGTGGAAAT AATAAAC Tr CTITT17A CTrAAACCAC TCTGTGTCAC TGAGCTGATT 10 TCACCTTTAG CCTGATAAAA TCATrGTCCT CTCCACCCTG ATT1CCTACAG GAGACTACTC ACCCCATAAC CTCAAAAACC TCTCATGAG GATGGTAAGT CACCTGAATC CTGAAGTGAA T;FACTCGCTA TTCCATTGGA ACTCATATAG GACACCAGAA TCTAGACCTC CAGAGAACAG CAGGACCCAT CTICAGAAAA TAAGAAGCAT TTGITCCCTG AGCCTGTTGA ATCAAAGTGC AATrCTATrr C'TTrGGAA TGTT1AAAAAG TGAATCATAA TATITTAAGCA GGTGAACCCA CGAGTAACAT AGCAGGGTCT TTCTTGTCAT TATTAGCTCC AACCTAGCAC 15 AGACA I1AAA GGTACAGATG TATACTAGCA TGAAACTGGG AGAACAGGAG CATrTCGAGCA ACCTTGAGAC CAATGGGCCT CTC=ATAAA ATGCACACCT CCTCTCACTG AGATTGAGGA AGGYI17'I1G TCTCCGAGCC TTCTCCCAGT AGAGCTATAA ATCCAGGCTG GCTCCTCCCT CCCCACACAG CTGCTCCTGC TCTCCCTCCT CCAGGTGACC CCAGCCATGA GGACCCTCGC CATCC'1GCT GCCATTCTCC TGGTGGCCCT GCAGGCCCAG GCTGAGCCAC TCCAGGCAAG AGCTGATGAG GTTGCTGCAG CCCCGGAGCA GATI7GCAGCG GACATCCCAG 20 AAGTGGTTGT 'FrCCCTrGCA TGGGACGAAA GCTI7GGCTCC AAAGCATCCA GGTGAGAGAG GCAGGCATGC AGAGCTGCTA AGTCTAGAGG GAAGGACGGG AGAGAGGTTC CAGAGTTGGG TCTCAGCAGT CTATGTCACT GAGGTGGCTT CACITAGAAT CTCTGGGCAT TGATIT7CTC ATCTAGAAAT TGAACAGAGA GCCAAATAAA CCTGAGAAAC 'TrTAITrCTC CAAAGACTTG ATTCCAAGAA ACATCTGTGA AATTCACTAA GTITAAGATA TGAAGAGACA GACTAG'rTAT TfTCTGGATCT AAACAAGTAG ACTrAG'rTGT AAAGAGAACA PPI1ACTCTA 25 TCTACAGAAG AGCITPTAAA AACTGCAGCC AAGCCTGAGG GTAAGTTCAG GTGTGTGTGT GATGGGGCAG GAATGCAAAA ATGAGAGCAA AGGAGAATGA GTCTCAAAT7 CTGTGTGACA AGCACTGCTC TGCGTG'FfA TTCCTATCGA CTGAGGTI7GT TCGTGCTACC GGCTGCAATG CAGCCAGCAT CACCTGTCAG CTAGCATGTG ACTCCCCGA GATTCTITT CTT1ACCCACT GCTAACTCCA TACTCAA'ITT CTCATGCTCT CCCTGTCCCA GGCTCAAGGA AAAACATGGA CTGCTATTGC AGAATACCAG CGTGCATTGC AGGAGAACGT CGCTATGGAA 30 CCTGCATCTA CCAGGGAAGA CTCTGGGCAT TCTGCTGCTG AGCTTGCAGA AAAAGAAAAA TGAGCTCAAA AT=GCTTTG AGAGCTACAG GGAA'TrGCTA TTACTCCTGT ACCTTCTGCT CAA'TrCCTr TCCTCATCTC AAATAAATGC CTTACAA GATrCTGTG TTCCACCTC 'TrAATGTGT GATATGTGTC TGTGTCAAGA CACTTGGGAT ACACGTACCA AAACGCAAAA TCAAA1TIT GAACAATATA CCTACCYJ7GC TATAGAAGAC CTGGGACAGA GGACTGCTGT CTGCCCTCTC TGGTCACCCT GCCTAGCTAG AGGATCTGTG ACCCCAGCCA 35 TGAGGACCCT CGCCATCCTT GCTGCCATTC TCCTGGTGGC CCTGCAGGCC CAGGCTGAGC CACTCCAGGC AAGAGCTGAT GAGGTTGCTG CAGCCCCGGA GCAGATrGCA GCGGACATCC CAGAAGTGGT TGTTTCCCT7 GCATGGGACG AAAGCTTGGC TCCAAAGCAT CCAGGCTCAA GGAAAAACAT GGACTGCTAT TGCAGAATAC CAGCGTGCAT TGCAGGAGAA CGTCGCTATG GAACCTGCAT CTACCAGGGA AGACTCTGGG CATTCTGCTG CTGAGCTTGC AGAAAAAGAA AAATGAGCTC AAAAYVITGCT TTGAGAGCTA CAGGGAATTG CTA FTACTCC 40 TGTACC'I1CT GCTCAA'ITC ='T GATCAAAATT MTACCTATT ATGCA=~GA TATATAAATA AGTATATAAA TGCACACACA GACACAGCAA TGATGGTGAA CAGTCTTCAT ACAATTATAT GGATGAATCT CATAAAATGC TGAGTTAAAG AAATCAGACC AAAGAACATA TACTGAAAGA 'VrCTCTCTAT ATACAAAGTT CAAAAATAGG TGGACCAATT CATGGTGGTG TTAGAAATCA GAAGAGAGGC TACCTTTGTG GGGAGGGGAC AGTTTAATGC CCAGAAGCGG TAAATAAGGA ATCCTCTGGG GAGTGGTAAT GATCTGGATG CTGGCTACAG 45 GATGTG'ITGG TTGTAAAAAT GCATTfTr ATATCTAGCT =FTCCATGT GTATATTATA CTTCAAAGAA G F7CAGTTAA TAA TTCTCA TGTCACTGTA GAGTAGCTCA GTTAGCCCCA GCAAGCCTCT GGCTTAATCT TGTITTTACCT TAAGCCATCA GTCATTTACA AGTAGGAAAA TTCACAGGGA AAGTrAGAGT ATAAAATCCA GAATGAAGGT TI7ACTGGGTA AGAGTCTCTC CAT=TCCAA AGCCCG TFTA TTTCTTGA'rr CCAGTTCrrA AGAAGTCTCA GCATTGTGTC 'TLTCATGT ATCTT1ACAAG AAGACAGCAT GTGCTTCTAA CACCTGATAC 50 ATTGTATCTA CCAGCACTI7G GTAAACAGAA AAGAACCACA TTrCfGT AGGAGAAATT1 TGGTGCCTAT TTCCTACCAG GCACCAATAA GTGGGACCAA TAGGTGGGAT TAAAGATACA GTAGAAAGTA 'VrrAAAACTT GCCAGGGGGC AATAGTCTGA AAATAAGTAA ATTGGTGCTA TAGAATGGAA GTTACAGGCT TC=TCTT TTCCCACAAG ATCTGCTCCT TGAGCCCCTA GAGAC'TITC TGTCTGTTAC TGTI17CTTCA TTCCTCATCT GCAGAGCCAG CCCTGAGAAG TGCAGACCAA AGCCAGGGAA GGCTCTGCAA AGATGTACAA ATGGAAGTCA 55 CCTTAATAAC CTCTGACTGC TGCGCATAAT ACATTTCACT CAAAAGAGGG GTI7AAACAAT GGAACAGAAT ACAGAGGCCA GAAATAATGC TGAACACTGA CAACCATCTG ATCYIGACA AAATCCACAA AAACAAGCAA TGGAGAAAGG ACTCCCTATI1 CCATAATGGT GCTGGGATAA CTGTCTAGCT ATATACAGAA GATTGAACCT GGGCCCC'TC C'IACATCAT ATACAAAAAA TAACTCAAGA TGGAGTAAAG AC ITAAATCT AAAACCAAAC ACTATAAAAA CCCTGGAAGA TAGCCTGGGA AATACCATTC TGGACATAGG ACCTGGCAAA GACTTCATGA 60 CAAGACACCA AAAGCAATAG CAACAAAAAC CAAATTGACT AATGAAACTA ATGAAACTCT TTAGTTGTAC AACAGATAGT TTATCTGTAC AACAAAATAA ACTATCAACA GAGTAAACAA CCTACAGAAT GGAAAAATIT TTTGCAAACT ATGCATCTGA CAAAGGTCTA ATATCCAGAA TCTATAAGGA ATrTAAACAA A1TTACAAGC AAAAAAATGA CCTCATTAAA AAGTGGGCAA AGGACATGAA CAGATGC'TrT TCAAAATAAG ACAPI'CACAC ATCCAACAAC CATATGAAAA ciATG'IMAAC ATCACTAATC ATT1AGAGGAA TACAAATCAA AAGCATAATA 65 AGATACCATC TAATACCAGT AGGAATGACT ACTATT1AAAA AGTCAGACAA TAACAGATGC TGGTGAAGGT TGTGGAGAAA AGGGAATGYI7 TATGCACTGC TAGTGGGAAT GTAAACTAGT TCAGCCATTG TGGAAGAGAG WO 00/62736 PCT/USOO/08020 61 TGTGGTGATT CCTCAAAGAA TGTAAAACCG AACTGCC'= CAATCCAGCA ATCCCATTAT TGGATATACA CCAAAAGGAA TAGAAATTGT M~ACCGTAA AGGCGCATGC ATGCATATGT TCATTACAGC ACTAMTACG ATAGCAAAGA CATGGAATCG TCTAAATGCC CATCAGTGGT AGACTAGCTA AAAAAAAAAA AATGTGGTAC ATATACATCA CAGAATAGTA TGCAGCCATA AAAATGAACA AGATCATCAT GTCCTITGCA GCAACATGGA 5 TGTAGTTGGA GGCCATTATC CTAAGCAAAT TAATGCAGGA ACAGAAAGCC AAATACCACA TGTTCTCATIT TATAAGTGAC AGCTAAATAT TGAGTACACA TGGACACAAA, GAAGGGAACA ATAGACATGG GACCTACTTG AGAATAGAGG GTGGGAGGAG GGTGAGGATC AAAAAGTACC CATAGGACAC TGTGC'TrrA ACCTGGGTGA TGAAATAATT TGCACACCAA ACCCCTGTGA CACACAA'TI7F ACCTATATAG AAAACCTGTG CATGTACCCC TGAACCTAAA AGTlAATGGT GGGGGGGTGG GGTTAAGCTA C1TTGTGGTA TAAATCTGAG CATTCATATr 10 AAAATAAAAT A'ITTACCTCA TTAGAGTAAT TAACA TTAT TAAGCAAAGA GCCAAGTACC TTACACACAT GATGTI'TAAT CTCACAATGA TCTIT7AATCT CATAACAACC GTCCATTGTA TGTACATATG TGGAAATTGA GCCTT1GGAGA GA FfAAATGC ATGGGGCATG CCATrGACT AGAAACTGGA AGCATCAGGA TTTAAACTCA GTTCTGAATG GTITTGTAGG CTrGTFIT TCCACATTAT AGCATGGCCT GCCATGAAGA ACAGGTCCTT TCTGGTGrJ'T GTCTT1GTTTG GTTTAAGTGA AGCAAATATT TATTTAAATA TTCAAGATAT GCTGTI7AAAT 15 T=TACTCAA AAA IMGAGT ACAGTATGGA TC'ITCTGAAG CCAAATAACT CTTAT7CAAT GCTTAGTrGA GAAATTAT GGAGTAGTTC TCAATITTTTA TGTAGTTCCA CTGCAAAGGT AAGTCTTATG GAAAGATTCA CTGTAATTf YTTCCTCAT 117GGACATCA GC TITCTT 'FrCCTCAGAC CCGCTGAAAG ATAAT17A AAATAAAAAC CTTGTTrA TATCAAGTGG GGACAT1T TCCAAATGAA AACCGTGTAT TCAT1TTATA TGATAAAATC AATGT7ATTA TITIAAAAT TTTGATTTAA AAATCA TAA AAATAAATT TCAGATATTA 20 CCTGAAATTC TACCATCCAG AGATAATAGT GCTTAAAGAT TTGATATATA GACACACACA CATATATACA TATATATCAT CCTAAACTTC TL17GTATAAA TGTATATAAA GTf1TAATA AAAACTAGGA GATFAATGCC C'ITTGAATGA AAATAAATAC AATGTGTATG C FTTAACATC TTGCCTAC ITTTATAACAT 'FTATCACAGC AGTCATGAGA TAATGATTTA CATGGTCAT? GTL1AGTAAGC TAATAGCTAA GTGCATGAAC TCTGGAGCTA GCCTCCCTGG A'rTAATCC CAGATCTGTC ACTGACCAGC TGAGCAATAC TAGGTAAATT GCTCTTGTTC 25 C'rrAG'ITTCT TCATCTGTAA AATAGAGATA AAAATAATAT CCACCTCATA GGATTGGTGT GAGCAT7AAA TGAGCATACG TATGTAGGCC ACTI1AACAAC AATGCCTTCA CATACTGAAC ACAAATATAC GAGCTGTTGT C'VrATTGGGC TCATG'I1TJT CCTACCACTA AGCCGCATGC ATGCAAGGAC CATGTTGGTT TJ'GTrCCACA 'FrGCATCCCC AACCTGGTAT ACAGTGTGCA TT1CAATAGTT1 GTTGACTAYI' ATTACTAGTG GCATAACA AATATCTGTT1 AAATGAGTGA AGAAATACCC ATTACTGCA AGTGTGTCTA ATATT1GATGG CATAATGGGG 30 GAAACTCAAA CTCTGGAGTC AAACAGG'I= TAAAACCTTA TrCCCTCATC CTCAG'ITATr GACG TTT TITTGGCAGG TGTGTGTGTG GGACAACT7A TTGAACTIT CTGAATT7CC AGCTTCGCAT ATATAAAATA GAGATAGTGA TTCATCFTG CAATGTATGG ATTGAGACA ATI'GTGTAAG TI17ATCAATA AATAGTAGCT ATfTTGTAT AAGTATTACA TATAATATCC AGGCCACTGC TIGCATAAC CCAAAAGGGG CACCATTCAT GCAGAATACA ACATAAATGG TGTCCCTGGA GCAGTGCAGT ATAGGAACCC TGAGGGGACC TACAGTATAC 35 TTTATAGTTC ATAGATTACA AATTATCCCT TTATCAGAGT CTCTCAAGGT TGGATGTATT TGAGGTCCAT AAGAGCAATT TAGGATTAAC AGTAGCTGCA GAAACCATCT GCAGTGATAT TCTCA'11TTA AATCCGCGGG AAAGAAGACA GCTATAAACT TGGGACCTGG GIM AAGCAT 'ITTAAATGCC AAGTJ7CACCA T = CTAAAA CACAACAAAT ACCCAGTGAG AGAGGGAGAA GGGAAGTAAA TGCCTCTGAA TAAGCAAG'I7 AATGTCAGTA GTIGTACTGT ATGCATATTG ATGAACAATA GAGGAACCAA TGTCCAATCA GATGAGCAGG ATA1TTGGCA 40 ATAACAAGTI' GCCTIGAGG AAAAATGATT 'rrC'rrGGCAA GTrCTrATC AGCATI'ACAA AGCTAAAAGC TACGCTI'ATC ATCACYI7ATA CTAGCATACC CTGTTGTGCA AATGCTGTCT GTGTTTGCAT CTGCTATTGT TGATGCCTGG TGCATGAATC AGGACTCCAG CCCACAAG'rr TTCCCAGAAC TTTCTTATGG CCATCATCTT TAAGTGTCTG GTGAACAGTC ATAGTTTGGT ACACAAAAGG GTCAACCTGG GGGATGGCTA GGGTrTGACT CAGTCGTTAC ATVTCAATAG AGCAGGAAGG GGAAATGGTG GCCTGTAACC TCAGGGAA17 TTGCCAGTTG 45 GTCCACCCCA CTCTCTCTCT CCTGCTCTGA GGAAGTGGCA CAGCCTAGAA CAGCACCACA GGTGAGAGAA ATGCAAACCC TAACCAGAGA AGCAGACTCT TTGCCAGTAG TAATAGYI7CA GGACCACCAC CAGCTITTAT TAAAATI AATAACACTC AAGTATTGGC AGAAAGAAAT AATCTTGGGT TAACTATAAC TAGAATATTG ACTCTTCCTC TGTGGAAGAA TCAGCCAATC ACA'rrrGTr ACATCAGTrC CCCTGAAGAA GAAAAATACA CTGATGT'rGC AGCAAGACAA A'ITTAAGCTA GATGTAAATA ACTrCC'TIA GCCTGTAATG CTAGGCTAAT 50 TACATATTGG AACTATI= TCAGGGAAGA ATTGTGTAGG G'TrTCAGGGA AGAATTCTGA AGAAAATATA GAGCTGAAAT GATCTTGCAG CTCACTGAAA CTGCAGGGTT TAGATCCACA CTGATACTCG TTFCTAYTATC ACTGTAATGA AGGCTGATGG AATAAGTAAA AATG FTGT ATTAGTATGT TITTACACTT AYPITGCAAGG CATAAATAGG TTAGGTITG ATCTTAATT AA'FrCTAACA TGTATGTGC ACAAGCTGTG AGCAGTTI'C AGGAGTTAGG TATCTGGCCA .TGACTGA'ITr TTCAGGAGTT AATCATCTGG TAGAAGGGTC ATACACAATA 55 GGAAGATGTG TGTGACAGGT TGTGATCATT ACTATAATCA CACAGAGAGC TGTAGAA'IM TAGGCTGGCA GGGTGGCTCA CGCCTGTAAT CCCAGCACTT TGGGAGGCCA AGGCAGGCGG ATCAAGAGGT CAGGAGATGG AGACCATCCT GGCTAACACG GTGAAACCCC GTCTGTACTA AAAATACAAA AAAAAAAAAA AGCCAGGCGT GGTGGTGGGC GCCTGTAGTC CCAGCTAC~r GGGAGGCTGA GGCAGGAGAA TGGCGTGAAC CCGGGAGGTG GAGCTrTGCAG TGAGCCGAGA TCGCATCACT GCAATCCAAC CTGGGCGACA GAGGGAGACT CAGTCTCAAA 60 AAAAAAAAAA AAAAAAAGTC ATGTTAGATC CAGAGGGGTA GCAACTGGGG CTGGGCTGTC AGTCAACTCA GTCAACTCAG TCAACTCTGC TCCCCCACAG GAGATGCCAG TGATGCATrT TCATGGCCAA CATTGTCAGT CAGCATCATT GAATTACTCC TGATTIATAGA GACACAGCTG CAAACGATTC CCCATFAAAT ATGATGTTC TTrGCAATGTT TGGAAGGTAC TCC'IThAG TAAGGGAAAT CCCCTCTrCT GGCTTGCTGA AAGTIT=C TTTCCA TTTT AAAAATCGTG AATTCC111 TGCAATATTG AGGTGGTTAT ATGGFI'TCTC TTCTCTAATC 65 TGTTAATATG GTGATI1'AAT GGTTAGAAAT TTTCTAATGT AAATTCCACT CATATI'GCAG AAATAAACCT AAACTGAGCA TGAGGCTATA TIT=TIATT GCT-FCTATAT 1TGGTTGCTA TACAGTATTA TG'ITAAGAT WO 00/62736 PCT/USOO/08020 62 TTGT'TCACAT ATATI'TGTGA ATGGGATTGG ACTATTITC CrrCTTGCCG ATITPATCT GGTTTAAA TTAAGGATAT =~AGACTTA TGAAATA'ITr GGCAAACAAT CCTTGGCAAG TAATIT1TG GGGAATTTGT TTGGCTATT TTGAGTATTA CCCAATATAT 'TrAATrAAG 'ITATTCTTAA TGT1TCTTA A FTAAAAAAA TTACCTACTC TAGAGATA IT C'ITrATGTAC TCCAGAT1T GTCTA1TIAT ACCACT1TC TrTTTTFCCTC 5 GATGAGTGTC ATAGATGTI'C ATCTATITP TTATCTTCTf TG.ATCTTCTC TTA'rTCCTTG TTTCTATTAA CTL'CTGAAGT P-FATTATI CTIT1TCCA CTTCC'ITATG G=TATrCITr TCAA T1TC TCTAACTTCT TAAG'ITGGGT G TrAATITT TAGCTTGCTT1 TGCTTITA GGATAAGCAT TAAAACTACA AATTI17CC'I1 GTTATrCTTT TGCTGCACCC CAAA FrGTTG ATATTCTAT TGTCTAATF CTATTCAAvr AGAATACYI AAAGMICTT TTTGGTI1T AAAAACTAAC TIT1AAA'IT GACAAATAAA AATTGTGTAT ATATTGTG 10 CACAGGATAT GGCT=GAAA TATATGTACA TL'GTGGAATG GCTAAAMTA GCT[AT-rAAT GTATGCATFrA TCTCACATAC TTATCATTI17 TTGTGGTGAG AGCTATGTGA CTI=GAACT TATGAG'ITAT TTAAATAT'IF TTAAATTATT AAGCATATTG GGA=IrAAG TAATFTACCT =TFrATr AACTTATAAC AAGTAGAACA GTTAACCTGT ATGATT1CTAC ATCATTGAAA TrATTGACA ITTGCTTCAT AGTCTATTAT ATGGTCTACT T'FrGTrCATG TIACATCTGT AGTAGAATTG GCTAATAGTr GAGTAAAGTA CACATATGTC TATGAAATCA 15 AGTGTAATCC AGAGAAAAAG AGAAA'TTAC TGAATATATT GTTCTAGGTG CTATFATATG FTGTCATGTT TAATCCTCAC CACAATTGTA TGAGGCAGCC ATAAflAATT CCAC'TIACA CATGAGGAGC CTGAGGGTTA AAAAAAAAGC TAGCTCTACT A'J1TGTAAAG AATGAAGCAA AGATACAAAT GAAGGCCCAC ATATCCTATA ACTAGATATT TAAGCATTTT AA'rrCAAGCT TTAAAACTGC TAAATAAAAT GTGCTCCAAT TrCTATATTG ACAGACATAC CTTCCTAATG AGCTGGGGIT CGAA TTTAGA AATC'ITTGAT GCTCAGAGT CCACACTGAA 20 ATGTGGAGGC ACATAGTGAG TT1GGTCCCCA GCCTI1CAGTC CACCCACCTT CTC'TACTA AATCACCTI1? CACATACATG TATGAACACC CCAGCCTCCA AGTCCAAACC CTAAACAAAA TGGGACACCC TITGTGCATAC ACAGAGACAC AGCCCATCCT CAGGAAAACC TGGAAAAGTC CATACAAGTT CTGGAAGCAA GC'rTGGGACG GTTTCAGTAG TGTGGTCTAT AAGGGAGGCC TCAGAAGACA GGTTTFC17A ATTCTGTGAA CTTCTCCCAC AGTAGAAAGG GTGCTGGAGG AGGGTCAGAG TGAGGACTC TAAAGCATGG GTCCTGAGTA GGGGCCACTC 25 TTGCCCAAGT CTAAGAAGGG TACTAGAATA GCACACTACT ACTAGATACT AGAACCCAGA TACAAGCACA GGTCTTCTGA AAYI'AATAAT AATAATAACT ATrACCATTA TTATACCAGT AGCTGTCATT TATJTAGTGC TTATTAT'ITG CCAGTCACTG TTCTAAAflC TTTACATGTA TTATACAACT GCCATATAAC TGCCATATGA GGGATGTACC CTCATTGTCA CCA'TPTACC GATGAGAAAA CTGGCATAAA ACG1TI7AAGT AACTGTCCA AGTTACAGAG C'I1AGTGAAG CCACAATGTT GCTCAA=rG CTCTCAAACT TCAAAGGGAT GGGAAGGACA 30 CCTAAGTCAT AGAGTCTITA AGAATCAGAG CTAGAAGGAA TCTrAGATGT TATCTAGTCA GCCTCCTCCC A'ITACAGTCC AAGAGAAGAT GGCCCTGAGT TACTTGTAGC TATIT=GCA TGTGAA ITGC AAGTGAATAT ACAT'rCTACT GAAGATAAAA GATA I=AAA GATATCGCTG GATATAGGAA CAGTGGTI AAATCTCTAG GCTTTAACTT1 YFCTCAGAAC AAGAAATCCT TTFGGTITTT AATCTATATG CACATCTGTA 'TTTCTCAA TrATCGGGTA GTAAAATATA AC2FTCTTC TGTAATAYVI' TTAAC1TA ATGAGTGTTC CTCATAATAG 35 AAAAGTTTGG AAACCATTGC TATGGGTATA TACTrCTAA AGGGATAGTA AYJTCTCTAG AATATTCATT TAATGCTCCA GAAGTAATTA GCACAATTGT GCAAGTCTGT GCATCATCAA CTATACATTC TGCCTGMTA CTCCAAATCC ACATGAAACT GATTATACAG TCAAAGGCGA GCCCAGTGGA GAGGCA'II1 TGGAGAC'I1C CTGGTACATT1 GAGACAGGGT CGGCCAGTCT GCGTrAGGGT CTTGGTCAAA ACTGCATTC TGAAACTAAA CTCAGATTGC TCT=IAA GGGGTCAGAA CTGATTCAAA TCTACA TrT TAAAAGCC117 AGATGTGGGG 40 CTITCCTAT TCCCAGTCTC CGCTATTGGT CT7GTGAAT CCACAGGCAA 1TIGGCCACA TCCT7GACTC TCTCTTATAT TAAGAATI'AA ACAGCTAAGT TCATGCAGAG GAAATATAAC AAAGGAGGGA CTrTCCTACA AGATCTITTGA AAAATGGAAC A'TrGCATAA GTCATA'ITTA GCCAGAACTG TTG'TrTATA TVTrCC1TTC TGAATACTTT GTT1ACACCTC CTCCCAGCCA ACCCCCCCCC TCCCTGACCC CAACTAGTCA GAGACCAAAG CCTT1CACAAT GG TI'ACACT TGAACCTTCC TGGCCCCACC CTCATCATCA CGCCTGAATA A FrACATrCA 45 CTGACTGGTC TCCCCTGCTT CCGTTTATCT CCACTCCTAA ACCCTCTGAC ACCTrAATCT TCCCAGAATA CCATTGTGAT CCTGTTCCAC TCTTGCTCAA G1TICCCAG AAACTAGAGT ACAAAC'rIA TAAGCYI17AG AGTI7GAAAGC CACTCTATCT CTTITrCATC CCCAGGTCTC TGCCAAGGCA GTATAACCTG TCCAACATCT CTAACTTCAA TACCrT7GTC TTAGATACTA GACTCTCCTC CTGGTTCTA A FFAAACCTG ATCTAGGATC TAA'TrrGCC TCTGAATTCT GTTGCCC'= GCCAAGTGAT CTCTTCCTCC TCTGAGCCGC AGCATCTCTG 50 AGCTGCACA cT-rAGCATAG CCATAGCACA CACAGCCTA GCTTFGCAGTT CAGGGTGTTF ACCTI7CCCTC CCCTTCCAGA TGCTGGATCC CCAGGGATAG GAACTCTGCC CTTATGTGTC CATAGCCCCT GGTAGTATGT CTTGCAGTCG TACATITCA GCAAATGTTT AATTGG2ITAA TTGAAGACAA CTGTCCCATG CCTTAAGCCT CTCYTITGC TAAACATGCC TGTGTCCT7 GTCAITrGAAC AACTATTG ATCTATTC TTCCTGACAT AGGGGTCAGT TCCGAGGATG CTGAAATCAA GAGACATAGC TI'ATTCTCTC AAAA'ITGCTT TCAAGAGTGA 55 TITTr1GTG AATTGAGAAC TGGCTGCCTA CTITGGACT ACCCACTTCA GCAAGAGTGT TTGAAACCAA ATCTAI17CTA AGTAAT1T1 TA'I7CCCT TCTCTATGGC ATTAGACACA CAGCTC'n= AAACTACCTT TCGTTATCTA TTAAACAGAC ATI1CAGTAAC TCTATAGACA CTGTCTAGCT ATATGAACT7 AGACAAACTA ATATCTCTGA GCTTCAGITT CTTAAAATr AAAATGAGGA CAATACCATC TATGGCCGGG GATrAAATGC TATGAGGAAT GTAAACCAGA TGTCAGGTAC CATCTCTCTA AAATCCAGAT AAAATGAATT AAAAATACTG 60 GCCGCAAACC CTCTCTAAGA GTTCTCAAAA TTCTCAGAGA GCTTAA TI' CATGCTCACC ATAGCACCGA Tr'CTTCTA AATA'TITGT TTCTACCAAA ATAITTTTGTC CCAA T=GC CTTTATGGC TATI12CTTCA TATCCACMT CCCAAACTAA AGAAGCAGCC CCTTCACCTT AAACTCCTCC TTCAAAGCAA CCTAAATACA GGTCTGGGTT TGTATTCCTA GTGGGATGI17 ACAGAGGTTA GTGTGATGCA GAGGAGGAGT CATGCTGTT AAATCCATAC TAGTCCCCAG AGGCCAGGCT GCTTCTGCCA CCCCTACCCC TCCCGCCACA GAGCTCTTCA 65 GCTTCTCACA TTTCTAGTTC TTCTCTCTCT ACTTTCATrA CCrTCTCTCT 'TITP~Tr CTTCTCATGT GCTCACGGGA GCAGAGAAAA TTAACTCCTC TAAG TTrCT TAACACAGAG TGCCTTAA117 ACATATTlACT WO 00/62736 PCT/US00/08020 63 ATTGTITGAG TTCCTGCCAA CACTACGTCT GTAGGGTCAC ACCTGCTATA TTAGAGGCTT ATCAAAAAAA GATAGCTTrC TCCTAAAAAG GGATTTGGAT GCCTACTAAG ATAACTGGAT GCCAAGATAA GTTTAACCTA ACAAACTTTA TTATTATTAT TATTATTATT ATTAGAGATA GGTACTTATT CTGTCACCCA GACTGCAGTG CAGGGATGCA ATAATAGCTC ACTGCAGCCT CAAAGTCCTG AGTTCATGCA ATCCTTCTGC TTCAGCTCCC 5 TGAGTAGCTA GGACTACAGG CATATGCTAC TCTGCCCAGC TACTTTTAAA AAAATAATTA GGGATGGGGT CTrGTTGTAT TGCCCAGGCT CGTCTCAAAC TTCTGGTC AAGCAATCCT CCTGCCTTTT ACCTCCCTAA TTGTTGGAGT TACAGGCATG AGCCACAGCA CTCAACCAAG ATTTAAAAAC TTTAAAAGA AATCACATTA CTTACTGTTA TCATCATTAT GGTTACTACC AGTGTTAAAA CAATTGGTAT TGAAAACACC ACTACCAGAT CAAGCTTCAA ACCAAGATGT CAAGTAAATA TTATTGTCAG ACCTCTGAGC CCAAGCCTGC AGGTATACAC 10 CCAGATGGCC TGAAGCAAGT GAAGAATCAC AAAAGAACTG AAAATGGCCG GTTrCCTGCCT TAACTGATGA CATTCCACCA TTGTGATTTG TTCCTGCCCC ACCTTGACTG AGGGATTAAC CTTGTGAAAT TCCTTCCCCT GGCTCAGAAG CTCCCCGACT GAGTACCTTG TGACCCCCAC CCCTGCCCAC AAGTGAAAAA CCCCCTITTGA CTGTAATTTT CCACTACCCA CCCAAATCCT ATAAAACAGC CTCACCCCTA TCTCCCTTCG CTGACTCTCT TTTCAGACTC AACCTGCCTG CACCTAGGTG ATTCAAAAGC TTTATTGCTC ACACAAAGCC TGTTTGGTGG 15 TCTCTTCACA CAGACCATGT GACATTTGGT GCCGTAACTC AGATCGGGGA ACCTCCCTTG GGAGATCAGT CCCCTGTCAT CCTGCTCTTT GCTCCATGAG AAAGATCCAC CTATGACCTC TGGTCCTCAG ACCAACCAGC CCAAGGAACA TCTCACCAAT TTTAAATTGG GTAAGTGGCC TCTTTTTACT CTCTTCTCCA GCCTCTCTCA CTATCCCTCA ACATCTTTCT CCTTTCAATC TTGGCACCAC GCTTCAATCT CTCCCTTCCC TTAATTTCAG TTCCTTTCTr TCTGGTAG AGACAGAGGA AACGTGTTCT ATCTGTGAAC CCAAAACTCC AGCACTGGTC 20 ATGGACTTGG AAAGACAGTC TTCCCTTGAT GTTTAATCAC TGCAGGGATG CCTGCCTGAT TATTCACCCA CATTTCAGAG CTGTCTGATC ACTGCAGGGA CGCCTGCCTG GATCCTTCAC CTTAGTGGCA AGTACCACTT TGCCTGGGTG GCAAGCACCA CCTCTCCTGG GGGGCAAGCA CCACCTCTCC TGGGGGGCAA GTACCCCCCA ACCCCTTCTC TCCATGTCTC CACCCTCTCT TCTCTGGGCT TGCCTCCTTC ACTATGGGCC ACCTTCCACC CTCCATTCCT CCCTTCTC CCTTAGCCTG TGTTCTCAAG AACTTAAAAC CTCTTCAACT CACGTCTGAC 25 CTAAAACCTA AATGCCTTAC TTTCTTCTGC AATACCGCTT GACCCCAATA CAAACTCAAC AATGGTTCCA AATAGCCTGA AAACGGCACT TTCAATTTCT CCATCCCACA AGATCTAAAT AATTCTTGTC GTAAAATGGA CAAATGGTCT GAGGTGCCTG ACATCTGGGC ATTCTTTTAC ACGTCGGTCC CTCCCTAGTC TCTGTTCCCA ATGCAACTCA TCCCAAATCC TCCTTCTTTC CCTCCTGCCT GTCCCCTCAG TCCCAACCCC AAGTGTCGCT GAGTCTTTCC AATCTTCCTT TTCTACTGAC CCATCTGACC TCTCCCCTCT TCCCCAGACT GCTCCTCCTC 30 AGGTCGCTCC CCGCCAGGCT GAATCAGGCT CCAATTCTTC CTCAGCGTCC GCTCCTCCAC CCTATAATCC TTCTATCACC TCCCCTCCTC ACACCTGGTC CAGCTTACAG TTTCATTCTG TGACTAGCCC TCCCCCACCT GCCCAACAAT TTCCTCTTAA AGAGGTGGCT GGAGCTAAAG GCATAGTCAA GGTTAATGCT CCTTTTTCTT TATCCAACCT CTCCCATCTC AGTTAGTATT TAGGCTTTTT TTCATCAAAT ATGAATACCT AGCCCACTCC ATGGCTCATT TGGCAGCAAC TCCTAGACAT TTTACAGCCT TGGACCCAGA GGGGCCAGAA GGTCATCTTA 35 TTCTCAATAT GCATTTTATT ACCCAATCCA CTCCCAACAT TAGAAAAAGC TCCAAAAGTT AGACTCCGGC CCTCAAACCC CACAACAGGA CTTAATTAAC CTTGCCTTCA AAGCGTACAA TAATAGAGTA GAGGCAGCCA AGTAGCAACA TATTTCTGAG TTGCAATTCC TTGCCTCCAC TGTGAGAGAA ACCCCAGCCA CATCTCCAGT ACACAAGAAC TTCAAAATGC CTAAGCCACA GTGGTCAAGC ATTCCTACAG GACCTCCTCC ATCAGGATCT TGCTTCAAGT GCCAGAAATC TGGCCACTGG GCCAAGGAAT GCCCTCAGCC TGGGATTCCT CCTAAGCCAT 40 GTTCCATCTG TGTGGGACCC CACTGGAAAT CGGACTGTCC AACTTGCCCA GCACCCACTC CCAGAGCCCC TGGAACTCTG GCCCAAGGCT CTCTGACTGA CTCCTTCCCA GATCTTCTTG GCTTAGTGGC TGAAGACTGA TGCTGCCTGA TCGCCTCAGA AGCCTCCTGG ACCATCACAG ATGCTTTGG TAACTCTTAC AGTGGAGGGT AAGTCCGTCC CCTTCTTAAT CAATGCAGAG GCTACCCACT CCACATTACC TTCTCTTCAA GGTCCTGT CCCTTGTCTT CATAAATGTT GTGGGTATTG ATGGCCAGGC TTCTAAACCC CTTAAAACTC CCCAACTCTG 45 GTGCCGATTT AAACAACATT CTTATACA CTTCTTTA GTTATCCCCA CCTGCCCAGT TCCCTTATTA GGCTGAGACA TTTTAACCAA ATTATTTGCT TCCCTGACTA TTCCTGGACT ACAGCCACAT CTCATTGCTG CCCTTCTTCC CAACCCAAAA GTGGCAACTC CTTTGCCACT TCCTCTCATA TCCCCCTACC TTAACCCACA GGTATGGGAC ACCTCTACTC CCTCCCTGGC AACAAATCAC ACCCTCATTA CTATCCCATT AAAACCTAAT CACCCTTACC TGGGTCAACG CCAGTATCCC ATCCCACAAC AGGCTTTAAA GGGATTAAAG CCTGTTATCA 50 CTrGCCTGTT ACAACATGTC CTTAAAGC CTGTAAACTC TCCTTACAAT TCCCCCATTIT TACCTGTCCA AAAACTGGAC ATGCCTTACA GGTTAGTTCA GGATCTGTGC CTTATCAACC AAATTGTCTT GCCTATCCAC GCCATGGTGC CAAACCCATA TACTCTCCTA TCCTCAATAC CTCCCTCCAA AACCCCTCCA TAACCCTTAT TCTGTTCTGG ATCTCAAAAC ATGCTTTCTT TACTATTCAT TTGCACCCTT CATCCCAGCC TCTCTTCACT TTCACTTGGA CTGACCCTGA CACCCATCAG CCTCAGCAAC TTACCTGGGC TGTACTGCCG CAAGGCTTCA 55 TGGACAGCCC CCATTACCTC AGTCAACCCA AATTTCTrCT TCATCCATTA CCTATCCAGG CATAGTTCTT CATGAAAACA CACGTGCTCT CCCTGCTGAT CATGTCCAGC TAATCTCCCC AACCCCAGGA CTGGCAAATT GACTTTACTC ACATGCCCCA AATCAGGACA CTAAAGTACC TCTTGGTCTG GGTAGACACT TTCACTGGAT AGGTAGATGC CTTTCCCACA GGGCCTAAGA AGGCCACCGT GGTCATTCT TCCCTTCTGT CAGACATAAT TCCTTGGTTT GGCCTTCCCA CCTCTATACA GTCTGATAAT GGACAAGCCT TTACTAGTCA AAGCACGCAA 60 GCAGTTCTC AGGCTCTTGG TATTCAGTGA AACCTTCATA CCCCTTACCG TCCTCAATCC TTAGGAAAGG TAGAACTGAT TAATGGTCTT TTAAAAACAC ACCTCACCAA GCTCAGCCTC CAACTTAAAA AGGACTGGAC AGTACTT'rTA CCACTTGCCA TTCTCAGAAT TCGGGCCTGT CCTCGAAATG CTACAAGGTA CAGCCCATTT AAGATTrCTGT ATGGACGCTC CTTTATTA GGCCCCAGTC TCATTCCAGA CACCAGCCCA ACTTGAACTG TGCCCCAAAA ACTTGTCATC CCTACAATCT TCTGTCTAGT CATACTCCTA TTCACCATTC TCAACTACTT 65 GTAAATGCCC TGCCCTTT TACAGTGCTG ATTTATACTT TTCCTCCAAA CCATCATAAC TGATATCTCC TGGTTTTACC TCAAACCGCC ACCCTTAAGT CTCTCTTAAA GTGGATAGAA GATCTTCAGT GACAAGGTAC WO 00/62736 PCT/USOO/08020 64 ACTCCAATAC TTCACCCTA ATAAAGCCCT ATrTI1ACT ITTATATTCA CTCTI7ATTCT TG'FrCCCATr CTTATGCCAC TCTCTACCTC TCCCCAGCTA TCTCCACCAC ACTATCAATC TCACTCACTC TCTCCTAGCC AYI1CTAATC CTTCTTTAAC AAACAATTGC TGGC'TrACA ATrTCTC'= CCTCCAAAAT CACCGAGTCC TCAA'TrACT CACTGCTAAA AAAGGGGACT CTGCATA'IM TTAAATGAAG AGTGrrGT-T ITACCTAAAT 5 CAATCTGGCC TGGTATATGA CAACATAAAA AAAACTCAAG GATAGAGCCA AAAACC11TGC CAACCAAGCA AGTAATT1ATG CTGAACCCCC TI1GGGCACTC TAATTAGATG TCCTGGGTTC TCCCGA'FrCT TAATCCTTTA ATACCTG'Tr TT-CTCCTTCT CTTATGCAGA CCTJ7GTGTCT TCCATTT1AGT TTCTCAAITC ATACAAAACC GTATCCAGGC CATCACCAAT CATTCTATAC GACAAATGYF 'ITAAGGGAGG AGACCACCCC TCATATTGTC TFATGCCCAA TICTGCCTC CAAAGAAAGA AGTAAAAATG AAAAGGCAGA AATGAAATCC ACAGGCAGAC 10 AGCCTGATGC CACACCCTGG GCCTGGTGGT TAAGATCAAC CCCTGACCTA ATCAGTTATG 'I1ATCTATAG ATPACAGACA T1GTATGGAA AAGCACTGTG AAAATCCCTG TCTTGTTCTG TTCCTCTAAT TACCAGTACA CGCAGCCCCT AGTCATGTAC CCCCTGCTTG CTCCCCCTGC TI1GCTCAATC AGTCATGACC CTCTCACGCA GACCCCCTTA GAGTTGTAAG CCCTTAAGAG GAAAAGGAAT TGTTCACTCG GAGAGCTCGG 'T1TTTGAGAC ATGAGTCTTG CCAATGCTCC CAGCTGAATA AAGCCCTTCC rrC'rTAACT CAGTGTCTGA GGGGTrGT 15 CTGTGTCTTG TCCTGCTACA GTCATCTA ACAACCCCAT AATATCACCC CTTACCACAA AATCT-FCCTT CAGCTFAATC TCTCCCACTC TAGG'TrCTCA CGCCACCCCT AATCCTGCTC GAAGCAGCCC TGAGAAACAT CGCCCGTTAT CTCTCCACAC CACCCCCAAA AATITCACT GCCCCAACAC 'TrACCACTA TTTCG'I1TTA rfTrCrrAT TAATATAAGA AGATAGAAAT GTCAGGCCTC TGAGCCCAAG CCTGCACGTA TACATCCACA TGGCCTGAAG CAAGTGAAGA ATCACAAAAG AAGTGAAAAT GGCTGGTTCC TGCCTTAACT GATGATATrTC 20 CACCATTGTG A TrGTTCCT GCGCCACCY-r GACTGAGGGA TTAACCTL7GT GAAATTCCTT CCCCTGGCTC AGAAGCTCCC CCACTGAGCA CCTTGTGACC CCCACCCCTA CCCACAAGTG AAAAACCCCC TTTGACTGTA ATITTCCACT ACCCACCCAA ATCCTATAAA ACAGCCCCAC CCCATCTCCC TTTGCTGACT CTATITTTGG ACTCAGCCCA CCTGCACCCA GGTGA1TCAA AAGC'rTCATT GCTCACACAA AGCCTGnI7G GTGGTCTCTI' CACACCGACA CGCGTGATAA TrATrATATI1 ACT=IAACT AAAACCCT CAGAGTCTCG CAGGGAAGGC 25 TGTATATATC TCATAAAATG TTGGGGCCCA CTGGATCAGA CAAGGCCACA AAGGCCAAAG GGAAGTAAAG ATCTCATTAT TTCTCCTAAT AA'TrCCCTG TCCITTGTCA TAAATGGTGG GTAGGCTGTT ATGGTGATGG CAGATITCT TTCCATAAAA TGTCCATAAT AGGACATFFTG AACAGAAGGG AAAAATCAAA TTGCTGAAGT TGAAAGAGGG CAATGCAAAG AAC'1TGGAG AAAGAACTGT ACAGAGAAGT CAACTGGCAG ATGGGAGGAA G'TTTAAGGGG AAAAATATAG ATGTCTAAAG AATACA'TrTA TTCATICC ACAGTGCAAT TTGGACAAGA 30 AGCCTCTTC 'FrGC'rrC'T CTATTCTCAT TAAATCATTA GAGCTCAAGC AATCCTTCTG CCTCAGCTTC CCGACTAGCT AGGACTACAG GTATGTGCTA CTATGCCCAG CTAATT1T AAAAATTAGA 'rITrAA'ITTG GTGAACTATT TCTGTAGGAA ACTACAATAA TACAGCCCAG GCACATlGAT CTI1GGGTGAA CAAATCAGAA, GGAATGAATA ATTCTGTGTT CCTGGGACTC TGACAA TrC ATGAACTTGG TACTCTGAGT AAAGCATAGG AGGAGTFATT TCATAAAATG TGGAGCACAA TCATGTGACA AAGATAATGG GATCCCCATT TCATAAATAA 35 ATCTGAAGT7 CAGAGAGAGT AACAACTGGC CAGGGTCACA TCACGGAGAC AGAGGCAGGG TTCCCACTGA TGCCTCTGAC TCCCTGTCCC AGGCCCTTCC TCCTCCCGCA AGCAGAAGTG CAGGGGGCAG AGCTGACCCT GTGCAGTGAA AATCTGAGGG CTGAGTTCCT ATTGGAACAC AAGTGAAAGA CTTCCTGGCT TCTAATCTCA GGATAAGGAC TCAGAGCTCC ATCTGTTCCA GCC'IAGGAT AAGAACCAGA ATCTrACACC ATGAAAGCAT GAAAGGTAAG A'TrGAGTGA GGAAAAAAAA AAAAAAAGTC TGTGT1TCAG ATTCAGTTCA CAAAGCAGTT 40 TCATACTTAA GGTACCATCA CAATAACCCT GTGGGGTAAG CAAGGCAAAT TFCATTCTTG 'T=~ATGGGC ATAGGAAGTA AGTCTCAGGG AGGI1?AAGAC CAAGGMIICT GGAGAAT1T ATATTATGAA TC'ITGATrA TGGGA TACT ATTATGTAAT TCCTAAGATC ATATAGGAAT CCTAGAGCTr GAATATAGAA CT117ArITT7 AAATCTATAT ACATCATAAT TACAAGGAGT AGTGTCCAT7 TGGGTTCCT GGCCCTGATG TGTTAGTGGA ATAAACATF TTGTCAGGGT TGCCATGTGT GTCTGTGCAC GTGTGCACTG TACACCTCCA GGGGATGTAC 45 CCTAAACCAC ATGAATGTGA TITfGCACATC CAAGA'ITTAC AGTGTACTAT AGGGAGAATC TITTGCAACA GCT=TGCTA TAATACAGAA TCTGAGATGT C'TrGAGAAA GAAAAGTGTA ATCATI'ACCA AAAAAT'rATr CTCATAATGT GTGCAAAT GTATGAAATC TATATTGGCC ATGGGACAAG GAGGTA ITC CAGCTAGCTT CTGAAAGGGC TCTA'I17CTCT CATAAGAATr CAGCTGTTGA CATTAGGTGA TATCTGCCCA GGTCATCAGA TGCCATAGAG AAAGAGGGTI' TGCTGAAACT TATATCAGCA GTGCACTGTA TGCTC'ITTCT GATrTATITG 50 AACATTCATT TATTGAGTGT CAAGTAATGC ACTAGATACT CCAGGGATCT GACACAAACT CTGCCCTGAA GGAGCATGTA ATCTCACTGG GGAGAAAACA AAACATATGA TAA TTCAAA ATAACAAACT AGGCAAACTA GTTAACACT'T AAAAAGCAGG C'TrATTCAA ATGCAAAATT GCATG'ITACA GGGTAACCTT TCAGTAAGAA GCCAGGAAGA GGAGCTCATC ATGGGTTGGA TTAGTAAAGG ACTAG'ITATA AAAGAAGTGG TGGGGTrGAG GGAGGCCTGA GATGAAATJT AAAGAATATG TAGAATCTAG GTAAGTGGAT AAAAGGTCTG GGGGCAGGGG 55 AAAGGAGAGC A=~CA317GT GAATCAAGGA ATTrCTCCAC CTG'1T11?AAC TCTTCCATAT GACATCAAAG AGATGTCACT TGCAGCTAGC ATI'CAGTGA TG'PITrCTTA CTAATAATAT CGTGATAAAA GAAACATI'GA CTATAAGAAA TAGGAATGGG TCTCATAAAA GGAAACAGCA AAACCCCCAA ACTAAAAAAC AGCGCAGGCT A ITTCTCTCT TCTCTCCTI1' TGCTTGGCAC TCATGAGATG CTAGGTGTGG AAGTCAGCCA ACTGAAAAAG AGAGGTGGCT GAAGAAGGTG GGGAGGCTGA AGCCAGTTAA ATAGGATGGT CCAATI7CACA GACGGCGAGG 60 CTACAGTGCA AATAGGACTC Th1CAACYG AGCAGGACCC CA ITACTMCA CTGGAGTI7AG AAAGAAAGGA GAGCGTAGAC TITGAACT TTCTATAAGA GTGTACCTCC ACAGTATACA GAAGACGACG TGAAA'1TTGA TCTGCAAGAA AACTGAGTCC ATATTCACAT ATGTATCAAA TrGCACTTC A'I=AGAAGT GTCTGTCATC AAGTACAGCA CTGAA'JTGAA ACTGAAAACA AGAGTCAAGA AAGAGCAAAG TCAGCCATCT TTATATITCCA CATGAATCCT TI1CCCTTTAT GGTCTFAThr G'IMCTCCTC AGAAAAGACA AAAAGCTGAG CTGTATAAAC 65 ACCTGTGGGC TGGGGGTTGA GGGATAAATG AGGGGCGAAA TGGAAGCTGA AGGAACTGTT1 GGTCAGGTAG AAATCTTCCC AGATGCACTG AAGGAAACAC ACTTCATGTT TGACGTAGGA GGTGCCACCA CACAAAACGT WO 00/62736 PCT/USOO/08020 65 TTCATGGAAG GATI17AAAGG ATCTCATGAT FTAGTATT CCAAGAAMJ TC'I=CACCA AGGGCGAT AATATGGGTC A I1CATACTG AAAGAAAAAC AAAAGATAAT AAGAGMIAA AAATI'GCAAA ACITGGAGTG TrAGTAGTAA AGGTAAATAT TCATTAGAGA TGAGAAGAGG AGCAAGGAAA TGCTTTCAGC TGGAAATCTC AGACAAGAGG CCAGGC'TrA GGAACCTCTG AAGATGAACA AATGTAAGCA AACCCTAGTA GCAGCAC'rrC 5 TCAGATTTTC ATGTGCTrAC CACTCAGAGA TGGTGTTAAA ATGCAGACTC TGATTCAGTA GGTCTGAGTG GAGCCTGAGA TTCTGCACCC CTAACAAGCT C'IMAGTGAT GCTTATGCCA CTGGCGCACA GACCCCACTr GGAGAAATh1r I1TGTGGTGCA TACGGTCTTT GTCTCCAGAT CTAATGAGTC TGAAGGACAG TGTAGATTrGA YTTTAAAT TTATGTTT1AT TrrTAATTTAA TPTAA1TIAA 'TTA~rrArr TKITAT1T TGAGATGGAG TCTCACTCTG TTGCCCAGTC CGGAGTGCAG TGGCACGGAG GCAGCTCATG CAACCACGGC CTCCTGGOfl 10 CAAGCGATTC TTCCGCCTCA ACTTCCTGAG TAGCTGGGAA TACAGGCACG TGCCAGCACA CCCAGCTAAT T1TGTATTT TTAGTAGAGA TGGGGTI1?CA CCACATTGGC CAAGCTAATC TCAAACTCCT GACCTCATcIA TCCACCTGCC ACGGCCTCCG AAAGTGCTGG GA'ITACAGGC GTGAGCCACC GAGCCCAGCT GTAGATTGAT TrTGAGCAGT GGAAAGTCAA GGAATT1AGAA GGCATGCTT1A AATGGAAAGT GAAATrGGAG AAAATY7AAA CTCATGAAAT AGTGGTGGTT ATAAACTCGT GATAAATTAT ATCCTGGGAT ATAATAAT GAGATGGTAA 15 CACKITTAGT 'ITAAAGAAAT AAGTGACACT TITITGTGT GACACAACTG TC FTAFCTT GGAAAGGACA AGGAGAGAAT GAAATATGGT ATGTCTTCAC AGCACCTIC AAAGGGAGAA CCAGATFTCTG AGGAGCTGGT CTCATGATGA ACTGTCAGGG TAAACCACAG TTCAGCAGCT GCAAATGTGC TTGCCAAAAT AGAGACAAAA AAATG'TrCT GAAAACAAAA TTTCACATAT GCCCTCCTCT GAGGTFGGCA TCATATCTrC CTGTGTATCT TGGGTGTAGC TrCTATCCTG CCAGAAM~A GACAGTAGAA ACCAAATGAG GTGATAAACA GAGTCA'TT 20 GCAGAAGAGT CAAAATAACC CAGCAAGAAA TGAAACCACA AATGCCCAAG GAGTCATTCA 'FrCACCATrC AAAAGCTAAT AGAAATGAAC ACAAACTACT ATGAAAATTC ACCCAAGAAC TI'AAAAAAAA AAAAAAAGGC TCATGGTGTT TAGTGTGATA GTATTCAMT TACCTErGAC TTGTTCTAAA AACACACCAT ACTTCTACCC CACCCT]?CCT CAGTGCCGTC ACACAATGGT TTCAGTGTGA AAAAAAAAAC CACGTFrACTG GAAAAGGAGG GTGCCTGGGA C~rGCCACTC TAAGCTGGTA GTCAAGGGTC TTGAGTTCTA AAAGCATACG CGTTAAGAGC 25 ATGATrCCTG GATCCAAATG AGTATGGATC TCAGcATrGC CA TTATTGT GACCTCAGGC TAITrA'rfr CTCTGTGCCT GTI1TCFI1AT CAGTAATGAA GATG117CATA GACCCTTCTC CCACAGAC'IT AAAGGCATAT TTrCATGATVFT AAGACATGTA AACCAPTCAT AACAGTATAC AACATGGAAT TAATA3TTGA TAAAGGFTTA TGATITATTGT AACTAACTCT GTCAM~GCT CAAGGCCTAT AGAAAACTTA CTrAAVrAGT TCAACTACAA AAAGAGT-rTG AATGTGATAT CCACCAAGAT CATA'ITCAGA CCTAGAATTC TGTGATTCTT ATGAATTAAT 30 ACAGCCTTGG TCAATAAATG AGAGCTGGGC AAATAATrCT TCTITGCTAG GCC'ITTCTAG ACCATCTGGT GAAGCATTCA AGACT-TATGT TATI1GGGGCC AGCCTFCCTT TCCAACTrCA ACTCCACAAC TCCTCAATAA GCCATGGGCT CAAGAAAG'IT CTGCTCAGTG GCCCCTGAAA AATGC'TTrCA TAGTCTCACT ACCATACCAC TGCTI'ACACA ATTTCCFrCC TACAGACTGC CTTCCTTTCC TGCTTTTCTC CATATACCTA AATCCTATCT ATTCTTCATA AGCAACC2FTC ITTATAACAT TTCTATAAC CACCAAGCCA AATGACC'ITT TCCTT=AA 35 ATATAGCACC CATrGGCCAT TACCATGCTC TGCCTTGTAT YITCTGAT-r 'TTrCnIC TATATI'CCTG TCTTAACTCC CCAGCTAGGT AATAA ITC CTGAAATCAG GGACCAGGCT GACTCCTCTr GCTGTCTCAA GAAAGCTTAG CAGTITCCAA CACAAAAATG 'PTCAATAAAC AACTATTAAT TGACTGATTA TAAAAAATCA GTGAACCATT AAACTTAATA TAGCAA'IMG CYI'AGCATGG TAA'ITAGCTr TTGCTAATA TTCTTCCAGC CAGTCTCTCC TCCTGTGCCT CAAGGACATC TTAAAAAAAA AAAATCTAGT TGATCTGCTT CCATCTAGTG 40 GCAATTAAAA CAGGTGGTTC CGGTAGCCAG AAAACAGCTC TGGGTAGATT GTGCCAGAAA ATAC'I=CAC TCAGTAGGTG CGAGTrTGAA AGAAATCTI7C ACATCTGTGG GTrTCCTGCC ACAGACATAG GGAGACCAGC CCAGAGAAAG AAGCCTTTCC TCACTAGACT CCATTTGCAC TAGTAAAGAG AAGACAGAGT AAYFAAAAAG AATAAAAAGA ACCTCCACTG ATCGTACATC CTCATCCAGT TACCCCTGCC CCACTTCTCC 'I1CACAGCCA AACATITAA AAGAGATGAC TGCTTG'I1CT GTCTCTAC~r TCTCATCCTC AGTAATGCTC AATGC'PTGGC 45 CGTCTGACCT CTGTCTTGAT GTCTGCACTG CAAATAGTCT CCCCACTGAC ACCCT-rGTTG CATCCAGGGG ATACTI1ACTG G FTCTCTTGG CAATGTT7GA AACCG1TCCC CM'~GT TTCCTTGGCA 'ITCATI'ACCC CACACTCT CTCCTC'rTCC TrCTCCCTGC CTGGCAACAT C'TCATr CTCTTTCCCT TAGGTGACTI? ATTAGATAAT GATGTTCCTC TGGCTCCCAT ACTCTCTCCC AGGTCCTCTT CCATITCTTrAA AGCACTCACA CCCTCCCTGG ATGATAGTAC CCACTCCTGA GATGGCAGTF ACCTCCTGAA ATGTGAGGGA CCCAAATCCA 50 CTTCTCCTGC CATAGCCTCT GTGCITJTGGA TAGGTCCAAT GAGCCACAGT GAATGATGTG CATACACCCA AAGCTCAGTA CAAAACTGAA CCCATGATCT 'I7ACCTCCAA AACCTCTCAT TC'TTfATGT TCCCTFrCTCA GAAGTAAACA GGACTACCAT CCGCCAGTTT CCAGGTGAGA AAGATGATAA TITGATTCTT CTCTCTCACT 'ITAGCCAAT TAACAGACAC ATFrCAGTT1AA TATCACCTCC TC'ITA'11CA TGAACCCATr CTTACTACTA GTTCCCTAGA CAGGCGCCAT CGGTTAAT CTAATAACTG CAAATGCCTC CAAAACAAGT CTC'TrGAAT 55 CCAGGCTCAC CTGTCTCCCA CACTrGCCAT ACTGCTCTGC AGGGTGACCT TATAAGATGC CAGAGGTAAG GCTACTCACT GTTTAAACCC C'FTrAGTGAT ATCCCAAAAG ACCTCAAGAT AAAGCCCATA TCACATGGCT TATACA ITAG ITATGATCT GGCT-FCTGGT GCCTCATITI? TCCCCACTI TTCC'rrrGCA 'TCTAAGCAA TGGCCCATAC TAAGTTTGTG ATTGGTAGGA TGGTTGCCCA AACCAGCATC CAATCCC'ITC AGAAATCATC TCACTTCATT TCTAGCAYJ TAAAGGAAGC TCAGTTGTCC AGCTGGGTAC TGAATATGTC ACCAAAGTCC 60 TccTI1rCATA G~rTATTTTA CTTAAACTCT CCTTCCTAAA ATTCCAGAGC AAGTCACTAA ACCCTAGATA CTGAGAAATA T1TICCATC TI1CATTTCTG CCAGGTGGGC CATCAACTI17 CACATGTCTG CATCTCCTCC CACTGTGCTA TTCTCCAGT AGAAGAAATT TGAGCTTCAA GACCAAACTG AAAAATACTT GCCTCCTTGG GGAAGCTGTA GGTAGAATTC ATGCTCCCTA TCITTrCCCAC AT[CTGAAG GACAATGCCT GTTAGAGCAA FTGAATGCAA ATAGTCAATT GAATAAGCAT 'PTATrCA'Tr CTCAATAAGT GCTTGTTCAA TrGAATAMr 65 CTrAAATAAT ATAT7FAAGA ACAAGAAGAA CACACCACAA TG'TFrAAC CCTCAGAAAA AATTCTGAGG TAATCAGAAA AATCTCCCTT TACATAAACT GCCCTITCT AATAGGGATT ACTTGTTCGT TCAYI7CATI'C WO 00/62736 PCT/USOO/08020 66 ATCAGCTCC ACTAGCACCA AAAAGCACAG CTCTGAAAGG AAGCTAGTAG ATrFATCACC TTATCTGGTC ATTGGATGA GGACCCCAGG TAAATAAACT ACTATGGGGT TAATGTGTCT AGCTAGAGCA GGAAGTAACT TAAGGAAGTA GAGAATGAAT CAGGAGATOT GGAAACTCCT CGCCACTAAT AAAACTTACC TTCTCTTGGA Th[CTTGCCT GAAAATAGAA AATAGAGAAA AGGCArrAGC AAAAATrAGA CAMTTTAAAG 'TITTTCAAGT 5 AAGGGAGAAG GAAGACTCCC ACTCTCAAAA CTGTC'IrG AAGTATATTA GGTATTGTT AGGTGGACCC TATCTGTGTC AAAGGAGATT TGAGGAACTG GCTTAATAAA CAGTGGTAGA CACTAATACA GAACAGACAT GTrGATGCAG ATGCCTCCTG AGGTI7CCATT1 CCATTCTCCG TGCTACTCAA. GAAGACAGAA 25441 TTGCTAAATT GCCTGGTGGC AAGACCCAAT ATGTCCATTC AAGTG'LTTAT CCCTTCCCAA TCTGCCATCT CATCCTACCT GCAGA'I1CTI? CCCflGAGGG ACAGCTGCTA ATACTGTAAA ACTATGTGCC ATTACAGCTC 10 ACAGCATCAT CTCTATGAGA ATCCACAAGA GAATr7CACT TTGGTCTTGT TGGTAGGAAT TGTGCAGCCT CATCTGAGTA ACTAATGTGT T=fATCTTA CAAACACAAG GAATATCACA TGGTT~CTCCT T7GACTGGCT GTAAGGAAAC TCAGAGCTAG ATCTGAGACC CTCTCCTACC AAGTATATAA AAC'ITTGTGA CATACATITTT TGTGCCATAA CTITCAACCTT GGTTCCAAAT GATITIGTA CCCTAAGT= AANITTTGGCT TTCTTTT~ TITTYTGTA CTCAATAAAA CATCAAGCTC ATTTATTATT GCGAAGAGCG AAACAACAAA GCTI'CCACAG 15 CGTGGAAGGG GACCCGAGTG GGTT1GCCCAA ATTGGCTTCT T==CTACT 'T=AATTAA TrrAA'TTG CTATACTGAA CACATTI'GT ACTG FTCTCA CATTCTI= GAAAAAAGCA GAATATAAAT AAGTAGATAA CTTAAAAAAA ACTCTrT1GAG CAGAAAGAAT CA'TrTGGGAG GCAATATATT TCAGTGGCTG TAAAGTGGCA TTCTAGAATC ATCCTACCCA GGTGAAAGCC CTATITGCC ACCrGTAGTG TAGTGTGTAT TTGAACAGCT ACTTTCTfl17 CTAAACTACA A=TCTTCAT CTGTTAAAGA GGCATAATAA TTGTATCATC CTCATTGGGT 20 TGATAAAATA AAATA'Tr7CC AAGTA TTAG 'ITCAGGTCCT AGCACGTAGA CAGTGTTGCA 'rrACTG'rrrr AATCCTTTAA AGTATTAAAG ACTACTATIT GAAATC'ITTT CTTCTAAAAT TCAGCCTGCT GATGACCAAG TGCACTTGAG CAGGGGGAAT CAAATCTGAA 'PTAATrCAG AITCTGGTTA GC'ITCACATA AATATTT TTAGGGATGA TGAACCTAAC AGCAATAGAT GAGTAAGAAT CTGTTCCTAC TGAGAGAGTJ? TCATTTTGAA GAAAAAGGAA CTAAGGGGGC ATGTG'I1CAG T7CATGCCC TGGTCTAACC CTGTGTGI7G GTI7CTGGTGG 25 GAAATTCTTC CAACCGAGGA AAAAACCAGT TCACAAATCT GAAGACCAGT GAYITAGAA GATGTATCTG GACTGGAGTC TAATCTCTGA CTCTGGGTCC TGCTGATATG GTA'TrGA GATrGGCCT AAAACATCAT TGCCCTGGTTr TCCTTAT-TTA CCAAACAGGG CCAATGGTAG TGACTAATCA GAAAATGATA ATGCCTGGTG CACAAAATGT GTCTAGATGA GCCCATGCAC AAGGACACAT G'TI'CTGGAA CTGTTCCTTA TrCC'TrTCCT AAAAGAAAGG AGGGAAAGTC TCCATACTAA GACTACTAGG GCAGGGGACA AAGTGCTAGA GTCAGAAGAT 30 TCATCTGAGG ACAGAAGAAT AGGGGTGAAG GCTCTAGTCA CTTCATrGGC TACCATGCTC TAAATAG'L1A CCTGTGCCCT TITCTAACT ATTAGAACCC AAAAAGCCTA TAAATTCTCT CTCTCTCTCT CTCTCTCTCT GTGTATATAT ATACATATAC ACACACACAT AGACACACAC ACACACCTAA ACACACACAT AGAGA'ITTAT GACITI'AC TITrATCCT-r GTAAATGCCA 'FrAACTATAT 'ITGTCTTAG A'TTAGCCTG GGAATGTAGC CAYI'ATTTCT ACCATTGCCT CCATAGGAAA AATACTCTTC ATGT1TTAAA GGACCAACCT ACAACTAAAA 35 TC'TrGGAAA GCAGAATCAT T-rGTAAGTTG GTGAAAATGG AAGATGTTGT 'ITTATAAATG AAGACTL'T TTITTTTTT L=GAGACA GGGCCTCACT CTGTTGTGGA GTGCAGTGGT GCTGTCATGG CTTACTGCAG CC317GACCTC CTGGGTTCAA GTGATCCTCC CACCTCAGTC TCCTGGGTAG CTGGGACTAC ATGTGCATGC TACCATGCCT GACTAAYITT TTGTATITI1 GTAGAGATGT GG'ITCGCCA TGTJ7GCCCAG GCTGGTCTTG AACTCGTGGG CTCAAGTAAT CCTCCTGCCT CAGCCTCCAA AAGTGCTGGG ATTAGAGGTG ACAGCCAAGG 40 TGCCTGGCCC ACAGATGAAG ACTATTTAAT GTTATCTTAA AGATACCCTA AGCTTCCTAC CAAGCCAGTG ATCThI1GGG GCTTCTGTfl7 TCTITG~rGG CATAACTGTA ACTAGCCTAA CTGCCCGTrA TCTGFITCCT G'TrTGCCCCA CACTGATI7CC CACAGCAGTr TTCAAGTTAT CGGTTGAGA TCTTGTACAG AAATGACTCC AAGGTAAAAA ATITAAAAAC AACCCCTCTA AT'TITPTAC CCTTGC'ITAT AAAACAGCCT TAGCCAGCTA ACCCCTCACT ACATGCAAAT GAGTGATr CTATTC'TIT GATTCTACAA ACACTTATTA AAAGATITA 45 GAATTCGGAA ATAAATAGCT TCCTATTAA GGTGACTTAC AGCCCCAAAG TCCT fIAAAAT TATTTAGACA ATAGCCACCT TATCCCAGGG GGCAGTGTGT AATAACCCAC CCTG'I7CTCT ATCCGTCAGT TCTGCCATCA TCGCCCAAGG TAGGAAGAAA GACAGGACAA CCGGGGTCAA GATTTGAAGT CTCAATGGAA AGAATAATCA GTGGTT1GGAG AAAACTGTCA TTCTTCTI= GCC'ITAATGC AGTACTI1GAT ACTrrATAC'IT AGTACTGTAT AGTACTTAGT ACTGTATAAT ACTATAAGAT AGTGAGA'TC AATCAGCACA GAA'ITCTAA TAGCAAGGGC 50 AGAGACATTT TAACTGCTCA GTGCTCTCAG GTFTATACATA GCTAATGAAG TTCTTGCATA TCAACAATCC CCACCCCCCT CACACACT'IT GTCTTTCTGG ATTGGTI7AGA AAACTTACCT AGCGCCCACT ATI7CTCAAAT TTAAATGAAA GATAAGATCA GAGTGGCACG CAATTAGGGA CTGATAAATA ATA'TT]GT AATTGCCAGT GTAAATGGAC AGGGGGCAAC C=IIACATAC CATATTCAGT GAACAGAATA CGTACTAACT ANITTGATGG AAGGAAAATT AAAATGACAA TCAACTGAGC CCACAGAAAG GCAACACAGA GCAG'ITGGTr AGCAATTG'117 55 TCGAGATCAT CCCTGAACTT GAAACAGGTA TATCTJTITT 'TTTT= TTGAGACAGA GTCTCACTCT GTCACCAGGC TGGAGTGCAA TGGTGCGGTC TCAGCTCACT GCAACCTCCG CCTCCCGGGT TCAAGTGAT~r C'VrCTGTCTC AGCCTCCCGA GTAGCTGGGA TTACAGGTGC CCGCCACCAC GCCTGGCTAA TIT=GTATr YT-AGTAGAG ACAGGGPTfC ACCATGTTGG CCAGGCTGGT CTTGAACTGC TGAGCTCATG ATCCGCCCGC CTCGGCCTCC CAAAGTGCTG GGA I1ACAGG CATGAGCCAC CACACCTGGC CAAAAcAGGT ATATC'PTAAA 60 AGCTGCCCAA TGTCCATGAA TGTTACAGCC TTGAATGGTT CTTCCAGGTG AGTTTGGCCA AATGTGGCAC CATACACCCA AGGCCTGCTG CAGGCTAGTG GG'rrGCTCAC ACTrTAAAGC TGAGACACAC TCATGCCTTA AGGTAAAGGG AGTGATAATC TGGGCAGCAG ATGTTAACTT CTCAAGGCAG TCCTCCTTCT CTTTnCCTCT CCAGTGACGG ATGGTTGGAA AGCATATATG GTGCA'ITTGG ITFAGAGCTGT GGCCTrTGGTG AATAGATACT TGGGAGAATA CATGGGAAT[ TCTCCCAGGG TTAATGCAAT GCCCATGTGT TGGGAACCAG GTGACTCTTG 65 AAGAGGTCAG GTATTGGGA GCAGTGCCTT GAAACCTTAG TGGACATTAG ACCCACTTCC TAGTGGAATr GTAGCATTGA AATCCAAGGC ATGTAGGCTC T'rAGAGGACA GAGATAGTGT GTCATT CAGAATTAAT WO 00/62736 PCT/USOO/08020 67 TAAGAGCAGG CCAGGCGTGG TGGCTCACAC CTGTAATCCA AGCCC'TrGG GAGGCCAAGG CAGGCAGATC ACGAGGTCAG GAGATCGAGA CCACTCTGGC TAACACAGTG AAACCCCGTG TCTACTAAAA ATACAAAAAA TTAGCTGGGC ATGGTGGCAC GCTCCTGTAG TCCCAGCTAC TTGGGAGGCT GAGGTGGGAG AATAGCTTGA ACCCAGAAGG CGGAGGTTGC AGTGAGCTGA AATTGCACCA CTGCACTCTA GCCTGGTGAC AGAGTGAGGC 5 TCTGTCTCAA AAAAAAAAAA GTATTAAAGA ATrrACATAAG AGCAAAGAAC CATrAGAATA TCTCACTTAG TTGTITATCAG CCTAGCAAGC TGCCTTGAAG GTAATAGACA TITTFAAAAG 'TTrATCAGAT GAAAAGCGAA AATCAGCCAA CCTGTITTAA TGAAGGTGTG TCCTGGGCTG A'TrACATGT CTCCAGGGAC TGATGGCTCT AGAATGTAAA GCTTGGCATC CTGC717GTGT TGAATCTATC ACATTTAATT TCCTGTGGGT TTCFTTT TFrTCTTT-C ACT-rTAAAGT TGTGTTC'TI' TCATGTGAAG 'rTAAACTCAC ATACC'TITT TTAATCTCCT 10 TGCCAGCCAA ATGATAAATG CCAACCCAGA GAATGCAGTA ACCATGACTG CCACTGGAAT GAAGAGGGGG TTATAATCAC CCTCCTTAAT CATTGAGAAA C3T=GTCCA ATTCTGAAAG AGAAATCAGT AAGGCACATA GCATGAGACC ACCAGCATrA TTTCCTAGT CTATCTCATG ATA TrGACT TITrCCTCC 'I1ACATCTCC CAGTAGTAGC CCA'TrGATG CCATTTGACA GATGAGGAAA CTGGCATGGG AAGGCCCCTG ATGAGTCTAC AGCATAGGCA AAGACTGGAC CAGCCTTGCT AGTCTAATGC CTACAGAATC TCAATGCCCA GATTTGTGGT 15 TCATAGAGTT CCTGAAAATG CACCTAAAAA TGTTGGCAAG AATGGTCATC GTrGTATrA GCTCCATGGA CTTGTrCAAT GACTGGAACT CTGAAACACA GAGAAGAGCT AAAAGCCTAA TACAACTTCA GGAAAAATAA AAGCCAATGA TCTGAACTGG ATAAT1'CACC AGTCAAAGGA AATCA'JTAAT GCTTTTACTrT TAAAGCAGTI' GTGCAAAAAT AAGCACI1TGA 'TIrACATG CCAAGGACCT GCACTAATIT CTTTCCAATG CAGTAGTTAC CAC117CCCTC TACTTCCTTC ACGAATAAGT AAAAGGGCAT GTTTAGAGAT ACTCTTGTAA GTGTAAACTA 20 AGTTCATTTG GGAGCCTCTA TTTGAAAATA CTGGTATAAA AAAAAATCTG TCTCCTGATA CTAACATTITG AAGGAATCTA CTT=fACA TATTGGCAGA GGGTCTGATT CTATCC'I1AG TTCTTCCCAT TACYITGATG AACCTTCA AGGTGA117TG ATCCCCACAC CCAAATATAT GATTGAGAGA AGGCTCAAGT TCCCAGGAGC TCCAGACAGA AGGTACCTGT TGGCTTGATG AAGATGAGGA GGAAATGAAC ACTAGCTAGG CCTTAAAGGG AAATGTCTCT GATAGGCCTA ATACACAGTC CTCTGCTAAA GGCCTCCCTG CCTCTCTCTG CTCATCCACT 25 CTACTCCCTG GCCCTGGGCA CGCAGCACAC AGAGATCAGC ATTTCTGACA GCTITCTGTAG ATCCTACCAT T7AAAGAC' TTGTCATCCA TGCAGATAGT CTCAGGAGCA GACACAGGTA GCTATTC'IM CACATGCTAG CT'AACATGC ATTGC'TA GCACCTATTG CCAGGCACTG TGTCAGGTGG AGGGTATACA AAGATGAACA AGACATGATT CTTCTCATAT ACAGATAGAT TTTGGAGGCA TrAGCT7AGT GATGATTCAG GAGTATCCAT TATh17GGGGA AGTAGGTGGT CATFAGTGAC C'I1TACAGG CATI17CAATG GGCTAACAGA GATGTTAGAT 30 TGTAGTGGAA TAGAAGAATG GGTAAAAAGT AAATCAGTGA GTrCAGAT TAGGAGTTAA GATGGCAAGA GGTGAGAACA AAAAAAGGAA ATGATTGTCA 'TTAAAGGAGG AGGAAAGACC AGCCAAAGAT FI17ACAGTGA GTTAAGCATA CAAATTTATT TCTAGGCCAC ATATrCTTAG CAAAACAACA TGTAAATGTT TATGTATGTC TIFTCCTCATA TCTGCTCATC CATCAGCTCC ATCGTTAAGA TTTCAG=1T CCAGGACAAA CTTACTCACT TTrGACATAT[ GGACTAGGAT TT1GACCAGAT TCCAGATGAT TCACAAATGG TI=CTrC'vr CCCAATTAAC 35 TCAGTTCC117 CTGAGCAGAT GAAGGTACAT GCAGAGGTAA AGCTGAAGCT GGCCAGGGGA TGGCTACAGT TCATGATCCC CAAATCTGGT GCTGATAGAG GCTCACACTG AATCACTTCA ATGAAAAAGA AAAAAAAAAA AAAGACAAAA CAGTA LTTCT GAGTAGAGAC CCTCCCTTGA GCAAAGGATr YI1AGCCAAA GCTGCCTGAC TACATTACTT GTGATATTGC TTCCAGGCTT TATITCTTG AGAATGATGG TGGGTGGTGA ATGAGAGATG AAGGCAAGGA AGCATTGAAA GCTGTGGGGA GAGGAGTAGC TACTCCAGGC TGCTGCCCTA GCTAAGGTGA 40 CCCTCCCCTT CTGCTGGAAG TACCATGCCA TATGGCCTCT GCATCAAGGG CTCTTATGGG ATATTCTCAG AGAATCTCTG CCGTICATC TGTrCTGATA TCTACCCAAG CATITGAAA AACATCCCAA TTCACTGAAG CAAGTCCAAC TTCCGTAAAT TCCAGTAGGT GGGTrGACAG TI1ATAAfl TCAATAAGGG ATTTTGATAG CACT]?CTAAG AATTAAACTA CTTAAACTAA TGCATCAGGA GCATACTTGT AGAAAAGTTA ACCAAAACTT CGTAAGTTCA GATGACA'ITG GT1TCTCCC ATATGGAGAT AAGG'TrGGCA GTT'AAAAATG AAAAAAAAAA 45 AAAAACCTAC CTFATTTCAA ACTITGAAAAG ATCAAGAGAT TGTGTITG TTTCAG'rr GTTATTCTCC TAAAAGTThrA TGCATGAGGA AAAGTAAAAG TGAYTTAAG AATAAGCCAA ATAAAACAAC CAAGAAAGAC CTCCACTACC CTGGGAAGGA AACTGGTGG TATTAAGTAG GACACCACAT AAAACAGGTG PI7ATTGAGAG GAGAAGAACC AAAATGTAAC TGAGGTTCAA CAAGACATTA ITATGCAAT GGCAATGAGA AAAATAAAAA ACACAGTATA ACCATGCTGT A ITGCTATAA GTCATGTTAC ACACTGGGAG ATGGCTTCAG GGGTATI7TGG 50 TI=rA=T TTGMTGGGA GG'TITICAA AAAAATTTAG TTAGAATAAG TCCTTTGAGA AACATCACAG TAGGTTAAAC AAAGTTAGGT TAAATTAGGC TCCTAAG= GACTTCTCAG CAAACTI'CTA CTGAATGTrC TGACTGTAAG CCCAGGATTG CATGACAAAA CCTCTAGTCT GAAGTT1ACTC ACCTT1GACAG GI17GGTTCTG GAGATGACCA G TTCCAAAT GGTCCACAGG TGGTITCTTC AATCCCAGTrf AAGTITTGTI1C CTTCAGAGCA GCTGAAGGCA CACTGTGAGC TGAAGCTGAA GTTTCCCAAA GGGTGAGTAC AGTCCATGGT ACCCAGCTCT 55 GGGGCCTCCA AAGGCTCACA CTGAATCACT TCAATAGGGA AAGAAACAGjT ATGGGGAAGA GTT1AAGAGGA ACTGACGCCT GGAUTTGAAT CCTAGCCCTG CCACTTGATA ACCATGTGCC TflTAAACAAG GTTACTTGAA CCCTCCAACT TCAG=TCTT CATCTATATA AGAGGAATAA TGAAA'I1GTG TrATCT1TAT CAAATTGATA TGGAAACTAA ATGTAATI'CA ATI'AGCATAA GTCAAGGACC TTAGAACAAA GCCTGACTCA TCAGAAATTC TAAGTAAACA TTAGCTAGTC TTCATATTAT TATCTTCAGC ATTATCTGTA GTGAGAATCC TFAAAGCCAA 60 ATAGGTGTAA CTGGGAATGA CCAGCTrAGT CGGGAAATAA CTATCACATC AGAGCCCCTG AGTCTACTAG AGTATITGGGA GCAAGATGTT1 CAGAGAAAGA GTGGGTCTCC ATAATAAGCC TTCTTTGCAA GGAGAGAATA TAAAAGTCTA GGAAGCAYPT TGACCTCAAT TCTGTCTTCT ATFCTAGCTC AGT1'CCAGAA TITrAACTCT YI-GATrTTG ACAACCCTCT CCAGAAACTG TATCTATrC CCTGTTCTGA TT1GGTGGTAC AATAGGTAAA T~rAAGACTT GGAAATCAAA G=mCACAT TTTAGACCCT GCCATGCCAT rrAGTAAACA GTACAAC'TI? 65 CATGTCTTAT TCCTCATCTG TCAAA LTTAA GCCATTATTG CTACCTTGCT CTAGAGACTT CAAGGAAGAA TGGACTCAAG GAATCAGAAG AAT'1'TGTA 'TrGGAAACT ATATGAGATG AGATL1AGGGA GAAACATGGG WO 00/62736 PCT/USOO/08020 68 AACTAAGAGA AAATGflATC TTTCATT GATPTAAAGA GTATCTATTA TATATCAAGC ATTACTCTGG GGCTTGAAGA GCTTAGAT CACCCTGTAG GACAAAATGG TAGGTAGAAA TTAATGGGTG GATTGTCATG TATGTGTGAT GTGYITAAT TGCT=fAAT TGATCAGTCT CCCTGTAGTA TGAATAATGT ATTTGAGGGG AGCTAATA AAATFGTGGA ACTCATCTAA TAAACTATTG CAAGAATCTA GAAGAAAGAT AATGACGGCA 5 ATGGTAGTAG AGTT]GACAAG TGGAAGACAA ATTAGAAAAA CACTAAGTI'G TAAAAATTGG TAGAATGTrA CCCTGCATAA ATGTrGGGGG AGrrAAGAGA GTCTCATACC AGGGTGCCCA TGTAAATGGT GATTCCACAT ACTGAGATAA GAAATACGAA GAGAAAAGCT GACTGGGAAC AATTGGTTF ATAGTCTTTT AAACATCCCA AAGGACATCC TTAGCATAYI? TGAGTTCAGA GCTGGAGATA GGCTTATCAG TCCAAAGATC ACATAGATIT GTGAGTCCGC AAAAGTCAGT AAGYTTGACC AAAGGATACA TGTAGATTAG AGTCAGAAGA GCAATATACA 10 AAAGACAAAA GCTGAGAAAT TATAGTAG'IT TATGGTCCTG GATAAGTGCT CATGAAGGAT CTCAGGAGAA ATGATCACAG GTAGAAAGAA TGAGAAAAGA GTGATATGAG AGAAACCAAG ACAAAGAAAA GTAAAATGTF AAAAATGAGT GAAATAGGCA TACCAATAAT TAAAAATGAG TAAAATAGGC ATACCAATAA CATAAGGGTT AAAAAATAGA GTTCAAAAAT GGGGTGAGGG TAAAGTATTA GGAAGGAGTC ATGGCCCAGG GATCAAGTGA AATGAGT'rAG ATCTATAGAT CTATICAGT TGGTrGACAT TrAAATGTAT 'fFFGGTI=A ATTCTTTATrT 15 GTITACAAAC ATTGCT1T= TAAAAAATTA AATTGTCCAA 'ITCAITFCAG GCTCACAAGC AAGTGCCTCA TATATACAGG CATTTTGTGG ATCCCAAAGA TGCAATGATA AATAGGACAC TTACTGATCT CAAGAAGTr TCAGTACCAG AGGAGACGGA CAAGTGAACA GATGACTTCA ACATAAGTGG GAGAAATGAG GAAGAAATAT GTGGAGCTAT CAGAACTAAG AAAGCTFCCT AGAAGAAACT GTCITTrGAAC AATGTCTTAA AGATGACATG TT~TTGGCC ATGTGCAAAA TGAGAGAGAA GGCCACCAGC AAAGTCAGTG TGCTACAGAG CACATGTGTT 20 AAGTGTGGAG AACTGCAAGA AGGAAAGGAA CTACTAGAAG GAAAAAGCAA GATACYJCT GGGTAACTCA GCCTCCTAAT GATAAATGGC ATAGYI17CTT CCAGACCTTA GAGTTCTAAT TAATCTAACA AGCTCATTAG ATCGTGAGCT TCT7GAGAGC GGGAATCTAC CATGCTAA11? CCTTATGGTA ACCCTGACAG CYI17TATCCC AACACTGTGC TTCTrGTGGT ACTCAAAAAG ACTTGTT7GAG AAGTGAGTCG AAACTTCATG CTGA=~ATG AAATCTTI1AC GGAAAGGTAA CAATATTGTG AAAGCAGAGC TITCTGATCA AAACTTCCCA YI'TCTCAGAG 25 TGGCTAGTAT CA=IIGTfC CAACCAGCTT CATGATAAGC TATAATGATT CCTGTGACTT TACCTAAGAA GAAGCAAAGA AAGGAAAGAG ACTTACCAAA CTGACACTGG GGCCCATAGT ACCCCACATC ACAGTFGCAG GTGTAA'ITAT TGATGATI17C TACACATTCT CCATGGCCAC TGCATGACCA GGGCTGGCAA GAAGCTTTAA GGAGGTCAGA AAAAAAATAT =PAATGTGA TTACA'r=A GTACTCAAAG TCAYTTT AGACATAGAT AACCTTrGT CTGAGATGAT TTAAATAATC AGGAAAGGTT1 TATrGTAAA TTCATAGCAT AAAAATCATA 30 TGCTAAAATT 'TrACGTATA AAATACACTA AGCATATAGT CATAGGCATI' TAT~rTGC1T TGGAATGAAA TT1ACCAATAC TAATATTCTG TAACACTTAT AGGAAACTTA GTGGCATACC TTGAAACTCT TGAAATT1ACT TGTr'ITrAAT GAGTGAGAAG GTrAAATGAT GACCTGACCT CAATCA1TI7C TGCATGCAAT TATTCTTGG CAATCCCTr CTITATAGAA ATCAAAGATT AAAAAGTCCA AATI17GCTAA AACGGTAGAG TCCAMTTTAT AAGAGACCAA ATTAACTATG GTTCATTATT AAAACATCAC TTGGAAAATG CTGGCTGTrT TGGAArTGTA 35 GAAGATITIA CAGAAATATT CATACACCAA AGATAGTGCA ATTI7ATAT AAAATTATAT AAGGTTAGAC CAAGAAGGAA GCACGCAGCA CCACACTCTC TACTI1CACAA TGTGAAAACT GAGGTGATGT GAGCCTAAGT TTCCAACTGG CCCCAGCTGT CAGCTCTCC TCCCCTGCCT TATTATCAAA GGCACTGATT GTCTAGCTCT TCCTCTGTAC TTCCTACGTA GATCTATCAT TITGATGTAA C'FrGATTrAG GGGTATAGCT TTGTGCACA GGGACAAATC ITACACACCA AAAATrCTTA GGAGTGACAC GATGCAAGAT TATATAGAGG GCTAGATGTA: 40 T=1AGAATG AACCAGAAGC TG'ITCTCATC CCCCCACCTT TCCATGGGGT AAATCTGAGT ATTCTCTTAA CCGTGGCCCT TCCTGAGTCT GAGGCAGCAT AGCCGTCTTG TCACTCCCTA CCTGTGTAAC AGAGGGCTGC CTrAGTTTG TGGCAGGCGT CATCGTTCCA YTGCCTGCA TC'IfrGTITC TCTTrGATATA GATCTCCACG CAGTCCTCCT TG317GTTCTT G'FrGTTGGGC TCACCATCTC CCCAGTrCTC TGCTTCTTCA GTAAGAGATT TGT'TGGTTCC CACCCACGTC CATA'VrCCTC CTATCTrCCG GATTCCTATC CAGTAGTAAG AACGACTGAA 45 AGGCAGAGTC TrCTCCAGAT ACTCAA'1TTC CGCCTTGTVF TGTATGGCAA CTAAATCTGT GTAATFGTCT CGGCAGAATC TTCTAGCCCT 'ITGCCAGTrC ATGGGTTT CAGAATAATG GTAAGTCCAG CAGTCGGTTC CATGATGTGC CAGGAAATCT GCAAGACATC AGTGTGACCT ATGCAGACTI ACATAATGTT ACAGCTAAAA AGAACCTAGC ACTACTCCAG GCTGAGCTAG ACACTrAGAG ATGAGGAAAC AGAGCCTAAG AGTGTATGTG ACCATCTCAG GATCACAGAA TAGTTG LTTG CAGATTTGAA GTAGAACCTA GACCTTCTGG CITGAATATA 50 AGATGCT= ATCTAAGGTT CTATITGAAA CAAA1TJAGT GG1TICTAG GITATITC TrATFTAATI1? TITTCTCAAA ATI'ATTTCAG GTGAAATTTA ACCAACATAT TTTAGACAYr CATATTTCTT TTTCTGTA GCTGTTAATG A TrACAACT AATTACCGTG TAATATCATA TAACTATACA AThrACGTAT AC'TTrAAT CCTGGAATCA 'TCTTGAAG GCCAACACAT ATGTACCTAT GGGAGAAGCA TAATAAGGAC AGGAAGAACA GTGACATACT TTAAGTAAC CTCTITACA TAAAAAACAT 1T7M1TAC CATAGGAAGA ACTGCFTCTG 55 GAAAAGCCCA ATATACCACT CAACTCTTAT ATATCTAACT GTATAATITI TAAAAAGAAC AATPACAAA GCCAAATGGT ATAGGATTAT GAAATrCA'rr AGATCATGTT CTATACACAA AGAGACTCAA CTGATGATGT TrAATAAACA TATGGACCCA TCAAATATGA GGGC=rGAA GATATCTAAT TAAACACATA ATrACACAAT GACTTCATAA TAATATATGG CA'ITCTAAGC ATGGTATGAT CTACATGAAT CACTATTTAA TACAGTAAAG AAACAGATAT AATTGATGGT AAAGAGCATC ATAAAATAAA CA FTGAAC AGAG FITrGA ATGAGCATTC 60 CACTAGAATG CAAGTTCTAA GAGGGAAAAA ACTGT7GTGT CCACTGCTGT ATCCTTAGTG CCTAGCATAA ATTTCACACA TI1GTAGGGAC TCAGAAAATA CCTGTFGTAT GAAAAGAGCA CTAAGTTT1CT ATGTGACACA GTGCAGACAT GGCATAAGGA ATGTGTGAAC GGGAGAGTTA GCATG'TrGC TI'GGCTAGAG CTGAAAATCC AGGCTAGGGA GAAAGAAGAC ATTAGTTTAC TTAGGAAATG AAAAACCAAG TTCAAAGCTA TYFGCTGGAGA GTCTTCAAGA ATCAGATATA AAATI'TGTCA CAACAATGGG AGAAGGACCA AAAAATGATA AACCCCCGTC 65 CCTAATAAG CTCGTA'TTGT AATTGTAGAA ATGACATI'AA TGTACACTGA ACTATGAATA AAAAATAGAA AATGAGGTGC TAAATATITG GTACAGA'ITG TAAGTACCTT1 AACAGAGATT TCTTAAL1AA CA'rrATTCCT WO 00/62736 PCT/USOO/08020 69 YFATAA'PTGA GGGA I1TTGT GGGG'rrAnG GGATGAAC TCTACAGCAT GGGCTATrAT AGGTrAAAAA TAGTGTTCAG GAG'1TTCTGG GGAAGAACTA AAGGTAAGAA GAAAAGAGAT GTTACAGAA GGGATAGAAT TAACAGCTCT GTGAAATAAT TTTCCCTTAG ACTATGTATA ACTAGTGGAT A TrAAGAAA AATGAATATA AGTAAAATAG ACTTAGCGAT ATATAAATAT CATAACATAC CACAACAGAG CATrGTCCAC CCCCACAACT 5 TGAAGATGTI' CCATAAGTCC CTCTGGGTGC TCTGACAT CCATGGAAAT ATCTGCAAAT GAAATACAAA ATTATATTTA GATGTATACT C317AAACCAC ACATYrATAG CCTrGAGGT GGTGCTTACA ACTTTCTTAA TAATCAGAAT AAAACACATA TGTCTACTAA CCCTGTCTGA GGTAACAGGT 'ITCTCAGACA TAGATGAAAA ATTACTTCAA AITTACATCA GAACTGATGC ACAGTITGT TIGTTCTAT TTTA'TFIA CGC'TrTAGTC TCAAGTTGCT AATCGGTACT GCCCTGAATT1 ITTrCTATGG TrTGGTAATr TJ17ATACCTG C'TrrCTGCT 10 GAGCTATTAG ATAAAACTAT TI'AATA=~A CTATGTATAT TT=AAAGT AITGTTGCTG CTrAATTAAC TATTGATGCT TATATI17AAT GTTATAGCCT CACTCTTGAT CATAATGGGT CAATGCCTCA AATACCTAAA AAAAAAAAAA ATI'AGATAGC CAGACACCAG GAAAGAAAAG TA TTT 'TI7AATAAAA AGAAATACCT 7MIGAGCAA CTGAAATGAC AAAGTCACAA ATITCCTGCA CACCrrAAAA TATACTTAAT GTAAATGACG AGTTAATGGG TGCAGCACAC CAACATGGCA CATGTATACA TGTGTGACAA ACCTGTATGT TGTGCACATG 15 TACCCTAGAA CTTAAAGTAT AA'TI1AAAA AAATTCTATC TTCCAAAGCA TATCACL1CT CAGGTAGACA CAGTGT'AT TGCAAAAGAT CTGA'ITTCAA TAGTATTTCT TCAAGAGTCT CCCCAGAGAC AAAGTCAAGA AGAGGAAATC AGCATATCTG AGAAGAAAGA 'ITTCAGGATC AC'rrrrITrG AGGGTCTGAG AAAATGTTTA G=F1CTATAT TATTTAAAAC CAGAAT7GAA ATGGGGTGAT TCCTATCC'IT GCCACCTGCC TCTACAACCC CAAGAGTITC TATCTGAGCA TCTAAACGTC T1TTAGGCTG AAAGGCTCAC CATGGCTTTG CTTGGTCCTT 20 CTCTAGTTCT TCTGCAGCCC ATTGAGCCTC TTGACTAGC ACAAGGGTCT CAGGTCCTTG CCCAAAGGGA GTGTGCTGTG CTGCAGGTAG ACTGCACTGA ATGTCAACAG AAAGCCTT1GC TTTCTTTCAT TTCTCTAACC CAGTCTCACA TCCTCCTCCT CCTCCCCTIT TCCCTCCCCT TCCTCCTGCA CTTCTCLTTC CTCThrCCCC ACCCCTYFTCC TAGACTGGCC TCTATTGCCT CCCACTGAGA CAAAAATGAA CTGCTGATCA GAAAGTAATG TGACTAGATT CTCTCTTCCT TCCCTCCTrT CTATCCTJTCC TI7CCATTCTC CTATGCATCT TTCCTTACCC 25 TCCTCCTCCT TCACTCATTG T-rGT-rGCTGT TCTT1CTTCCT C'ITCTIT=C CTCCTGCTCC TCTTCTrCTA CTTGTTCTTG TTCTTGT1TT TG'TJ7GGTTC TTGTTCTCCT CTTCCTCCTT CTCTCTCTCC TCCTCCTCCT TC'TrrCCAC CACCCTCCCC TATCTTTC ATAAATGCTA AACTAACTCT TGGCTACCTG TGGTAAATGG CCCTTGGAAA TTGCAAATAC TACAAATCAA AACTGCATIT CAGACATA117 TATGATGITT? GCAAAACTTC AGTAGAGCTA AGCAGTGGAC 'rrGACTCGTr TCGGTT1CCTT CACCTCCGTC TrCCTrTGCT CACCACCTAG 30 TGGACGTCCT TGTTAGTGGC ACTTCCTGAA GTTAACCCCT GAAGAGAGCC CATGCTCTCT AGC'TPTTCAC CGTGTAGGTT TGGGAGCCTA CAAGTACCTT TAATATrCTT GGACTATAAA ATGAGATGGT YT7ATAAGAC TGCATGTGAA ATTAGGACCC ATATGATGAA GGACAATAAA AAGGAAGACC CACTGATGTG AGTCAATGAG TCAAATGCAA ATCAGATTTG CAVII=AGG AAAATAATAA TAACAACAAC AAAAACTCTG AAGCTCAGCG CCCCATAThT ATTATATTGT PrTAATC'ITTA TAACAGCTCT CTGCTATAGA TATGATrATT ATCCCCATTC 35 TAAAGAGTCT CAAAGAGGTI' AAGAAACAAA TTCAAAAACT AGCGAAAGAC AAGAAATAAC TAAGATCAGA GCAGAACCAT AGGAGGTAGA GACACGAAAA AGCCTTCAAA AAATCAATAA ATCCAGGAGC TGCAT=TGA AAAGATTAAC AAAATAGATG GACCACTAGC TAGACTAATA AGAAAGAAGA ATCAATAGAC ACAATAAAAA ATGGTAAAGG GGATATTACC ACTGATCCCG TAGAAATACA AACTACCATC AGAGAL1ACT ATAAACATCT TT1ACACAAAT AAACTAGAAA ATCTAGAAGA AATGGATAAA TTCCTGGACA CATACACCCT CCCAAGACTA 40 AACCAGGAAG AAGTCAAATC CCTGAATAGA CTAATAACAA GTTCTGAAAT TAAGGCAGCA A'ITAATAGCC TACCAACTAA AAAAAGCCCA GGACCAGATG GATTCACAGC CAAA'I7CTAC CAGAGGTACA AAGAGGTGCT GGTACCATTC CTTCTGAAAC TATT1CCAGAG AATAGAAAAA GAGGAACTCC TCCCTCACTC A'ITTATGAG GCCAGCATCA TCCTGATACT AAAACCTGGC AGAGACACAA CAAAAAAAGA AAATTTCAGG CCAATATCCC TGATGAACAT CATTGCGAAA ATACTCAATA AAATACGGCA AACTGAATCC AGCAGCACAT CAAAAAGC=r 45 ATCAACCACA ATCAAGTTGG C'FrCATCCCT GGAATGCAAG GCTGGrrCAA CATACACAAA TCAATAAACA GAATCCATTA CGTAAACAGA ACCAATCACA AAAACCACGT GATI'ATCTCA ATAGATGCAG AAAAGGCCTT GGATAAAAr17 CAACACCCCT TCATGCTAAA AACTCTCAAT AAACTAGGTA TTGATGGAAC GTATCTCAAA ATAATAAGAG CTA'ITTATGA CAAACCCACA GCCAATAGCA TACTGAATGG GCAAAAACTG AAAGCGTTCC C'TrAAAAAC TGGCACAAGA CAAGTATGCC TCTCTCACCA CTCCTGTTCA ACATAGTA'IT GGAAGYI'CTG 50 GCCAGGGCAA TCAGGCAAGA GAAAGAAATA AAGTGTA'ITC AAATAGAAGA GAGGAAGTCA AA'ITGTGTCT GT[TGCAGAT GACATGATI'G TATATTTAGA AAATCCCATT GTCTCAGCCC AAAATCTCCT TAAACTGATC AGCAACTTCA GCAAAGTCTC AGGTrACAAA ATCAATGTGA AAAAATCACA AGAATTCCTA TACAGCAATA ATAGACAAAC AGAGAGCCAA ATCATGAGTG AACTCCCATr CACGATTGCT ACAAAGAGAA TAAAATACCT AGGAATCCAA CTACAAGGA ATGTGAAGGA CCTATTCAAG GAGAACTACA AACCACTGCT CAAGGAAATA 55 AGAGAGGACA CAAATGAATG GAAAAACAYr CCATGCTCAT GGGTAGGAAG AATCAATATC ATGAAAATGA CCATACTGCC CAAGGTAATT TATAGATTCA GTGCTATCCC CATCAAGCTA CTACTGAC11 TrTTCACAGA ATTAGAAAAA AACTAC'1TTA AATTTCATAT GGAACCAAAA AAGAGCTrGT ATAGCCAAGA CAATCCTAAG CAAAAAGAAC AAAGCTGGAG GCATCATGCT ACCTGACTC AAACTATACT ACAAGGCTAT AGTAACCAAA ACAGCATGGT GCTGGTACAA AAACAGATAT ATGGACCAAC GGAACAGAAC AGAGGCATCA GAAATAACAC 60 CACACATCTA CAACCATCTG ATC'TGACA AAGCTGACAA AAAGAAGCAA TTGGGAAAGG ATTCCCCAYT TAATAAATGA TGTTGGGAAA ACTGGCTAGC CATATGCAGA AAACTGAAAC TGGATCCCTT CCTTACACCT TATATAAAAA FFAACTCAAG ATGGATL'AAA GACTTAAATG GAAGACCTAA AACCATAAAA A FrCTAGGAG AAAACCTAGG CAATACCATT1 CAGGACGTAG GTATGGGCAA AGACTTCATG ACTAAAACAC CAAAAGCAAC AGCAACAAAA GCCAAAATTG ACAAATGGGA TCTAATTAAA CTAAAGAGCT TCTGCACAGT AGAAAAAAAA 65 AAACTATCAT CAAAGTGAAC AGGAAACCTA CAGAATGGGA GAAAATTT GCAATCTAITr CACCTGACAA AGGGCTAATA TCCAAAATCT ACAAGAAACT TAAACAAA IT TACAAGAAAA AACAAACAAC ACCATCAAAA WO 00/62736 PCT/USOO/08020 70 AGTGAGTGAA GGATATGAAC AGATGCTTCT CAAAAGAAGA AG'ITATGCA GTCAACAAAC ATATGAAAAA AAGCTCATCA TCACTGGTCA TTAGAGAAAT GCAAATCAAA ACCACAATGA GATGCCATCT CATGCCAGTT AGAATGGCGA TTATTAAAAA GTCAGGAAAC AACAGATGCT GGAGAGGATG TGGAGAAATA AGAATGCMr TTACAGTG'r GGTGGAAGTG TAAA'FrAG'rr CAATCATTGT GGAAGACAAT GTGGCGAMV CTCAAGGATC 5 TATAACTAGA AAAACCATr GACCCAGCAA TCCCATTACT GGGTATATAC CCAAAGGATT ATAAATCATT CTACGATAAA GACACATGCA CACTFATGTT TATTGAGGCA CTATTCACAA CAGCAAAGAG TTGGAACCAA CCCAAATGCC CACCAATGAT AAACTGGATA AAGATGATGT GGCACATATA CATCATGGAA TACTATACAG CCATAAAAAA GGATGAGTTC ATGTCC'ITTG CAGGGACATG GATGAAGCTG GAAACCGTCA TTCTCAGCAA ACTAACACTG GAACAGAAAA CCAAACATTA CCCATTCTCA CTCATAAGTG GGAGTTGAAC AATGAGAACA 10 CATGGACACA GGGAGGGGAA CATCACACAC TGGGGCATGT CAGGGGATGT GGGGCTAGGG GAGGAACAGC ATTAGGAGAA ATACCTAATG TAGATGACAG GTJ7GATGAAT GCAGCAAACC ACCATGGCAC ATGTATACCT ATGTAACAAA CCTGCACG'JT CTGCTCATGT ATCCCAGAAA ITAAAGTATA ATITAAAAAA AGTTTAAAAA AAGAAAGT-rG CCTVAGTCAC ATAACTAGTA AGAGACATGG TTGGGAATVT GAACAGAGGC CAATCAGTTC CAAATCCATG CTCTTGATCA TTAAGCTGAA CTTATGGCAG GAACTTGGAA GACATGGTAA AATGGGGAAA 15 AACGTGGAGC CAGGGAGACT TGTGAAAGTG CCAGTGCTCC CACTATACCC TGAAAGAAGT ATCTAGACT AC'TTfTCT AAGTCCTCTC CTCTAATTCT CTCAATCTCT CTCTCTCTr CTCTAAGAGA TGGGAATGCT GCTCTGTCAC TCAGGCTAGA GTGCAGTGGT GCGATCATAG CTCATrGCAC TCAAGGAATC CTAGGGTCTA GTGCCCCTTC TCCCTCAGCC TCCCATGTAG CTAAGACTAC AGGCACATGC CCCAACCCTC GACTAATTT TTrrA'=rf ATT=IGTAG AGACAGGATC TCACTATGT GCTCAGGCTG TAATTCTGTC 117GAAGCTTG 20 TCCAATCAGG CTTTCAGCCA CACCAATTCC CTGAGACTGC TCTCACCAAG GTCCTACACT TCACTAACAC AAACAGCCTA TTCTCCATCC TCATC'ITACT TCACCAGGGA GCTCCTGG'I17 TrfCCTCCTAC TTCACTGGCT ATTTCTTCTG TATCATGTGT TGATrCTCCC TCATCTCCCC AACCTCCAAA CCCTTGGAGT ACTCCAGAGA TCACCGCTIT GCTCTTCTGT GTCTAACCTC ACTAACTTGG TGGTCCAATTr CACACTCTrG ACTfTGAATA CCATI17AAAT GCGAACGAAT TCTAAATT1CT GTACAACCAG AACCA'ITCTC CTGTAGCCAA ATGCCTACTC 25 AACATCTCCA TCCCCAAACA AATAGTTG TT1CAATAAGC CTCTCATATT TTACATATCC CAAACTGAAC TTCTGAAT' CTCCTCCAAT CTGTAGGGCT CYrCCCACAG CCTTTCCATC TCAGTGGATT ATAACTCCAT CCTTCCAGTT ACTCAGACCA AAACT=VGG AGTTAACTGA GACACCTCTC 3T~ITCA CAAGTCATAT CCAATGTGTC AACAAA'I1TT GGTAGTGGAA ATATTGCGGG AITrAAG AAATCAGAGA GACCGATGGG GTI7CAGGAGG ATATI17ATTA TTTAGGTGCA CTGGCCAAGT CAGATT1AACA TCCAAAGGAC TGAGCCCTGA 30 ACAAAGAGPr AAGTTACCT TT-AAGCATTr TGTGGGGTGG GAGAGAGGGG TATCTGTGCA GGGGGAAGCA TACTACAGAA GTGAGAAATA AAGACAGTI'A TTCAATrAAT TGAGACATGC ATTACATCAT TTCTrACT TCAAGAAGAA ACATGYITG CGACTGAGT Tr1ATCTGTCT AGTGACCTTG CAGCTGCACA GCTAGAGAAA CAGGGTCYPC ACAATGCCTG GGAAAGGAGG AGAGGTAAGT CTCACTAGCC ACAGAAAAAC AGGCAGTTAA TTITTAAAGG GCTCCAGCTC 'ITrCTC=TC TCAGGGGGAG TTGGGTmlG TI1ACATACAA CTGAGTCC 35 GCTTACACAT TA'TTAA'TI' CPI=AATTC CTG'FrCCAAA AGAAGCCAGA TACAAAAGGT TACATGFITGT CTGA317CCAT TTATATGAAA CATATAGAAG AGGTAAATCC ATAGAGACAG AAAGTAGATT AGAGGYTCCC AGGGGCTGAG GAAGAAATGG GGACTAACTG CTTATAGGGT ACAGAGT=T CTTCTGATAA AAATATTrG GAACTAGATA GACA'TMrGT TAGGCCATTC TTGCATTGTT ATAAAGAATT ACCTGAGACT TGGTAA'TTTA TAAAGAAAAG ATGTITAAUT GGCTTACACT TCTGCAAGCT TT1ACAGGAAG CATGGTGCCG ATATCTGCTC 40 AGCTTCTGGT AAGGCCTCAG GAAGCTrACA ATCATGGCAG AAGGTGAAAG GGGAGCAGGC ATATCACATA GCAAAAGCAG GAGCAAGAGA GGGATGTGGG GAGGTGACAG TCACTITAA ACAGCCAGAT CTTGTGAGAA CTCATTCACT ATCATGAAGA CAGTACCAAG AGGATGGTAC TAAATCATT1C ATGAGAAACC CCACCCTCAT GATCAAATCA CCTCCCACCA GGCCCCACCT CCAACACTGG GGATTACAAT T~[GACATGAG A'ITTGAGTGA GAACACGGAT CCAAACCATA TCAGAGATGG TGGTTATACA ATGCGATAAA CGTCACTGGA TTGTACACTT 45 TAAGATGGTT GTTATGTr GTGTGAACTT CACCTCAATA AAAAAAAATA 'TrTAATGTAC ATTCAGCCAA AAGAAGAYI1 GGAATAGGAA AGGTCATGGA GATATATTAA CAGCCATTTG ATGGGTGGTA AGGAAAAGAG TGGTTATTAG ACTGTITGT GGCCCTCAAA AGGTAGAACT AGATCGAGT7 GGTGAGCAYT ATAAAACCAT CACAAAACCC TGGAGAGAGG ACCCAGTGCT GAAGAACCGT TTGCCTGCCA TGAGACATGA GGGAAGTACC AGTGAATGCC A'I1GAAAGCA GCATCCCTGG GTCCAAGGGA TGGTCAAAGG ACCACTACCC AACCCTTCCC 50 TAGCCTACGC CTCCATI1ACA GATGACCGCA AGAMTIATT GCTCATTGCT GCCAACCAAG GCTGCACTCA CTGCAGTIGC TATCAGThTA TCATGGGTAA AAGGAATGTG CAGTAGAGAA CTAACTAACT GCCCACCTAC CTCCACAATC CTATCAGGAC AAATCACCAT GGCTCACATT1 TCCTTACATT TGGCATGTAA GCCCCTCTTA CTGTCTGTCA TCTATCTCCT ACACAG'ITCA CCTAAACTGT TCTCTCCTGA CCCAACCTTG ATITTCATCC CAAATGCTTC CTI1GCCATCT CTGGGATTCC TGTCTTCACC ATCACCAAAC TCCCCTCAAT CTTICCAGTTT 55 CCTGTTCAAA CTITTCTCCT ACCTCCTTGC TrFGTCATrA GCCCGACTGC CTCCCTAGGA CATCAC'YrCC CCTGCAGATC TCTCAAGATG ACAATA'TrTA TTCTCCACAC AGCACATACT TCAGGGTT1GG AAGGCAGGGG CAATCTJ7CTC C=fATAATG AGTGCCTCT ATATATGYT- ATTCATCTGC CCTCTTGTAA AACACACACA CACACACACA CAAAGAAGAA ATAAAATAAC TCTGCTTCTT TGAAGCTTGT GACACTGAGA TAAACCATCT CACTGTCCTC ATTGTAGTGA CCTCTCAACT CCTCATGCAA GA I1GGCTTT GGCACCTAGT TCCTGATCTT 60 CCTTTCCCTG TAAGCAC'ITC TCATAGTC'I17 ACGGGACTTC ACCATCCATG GCACAACCAA TACCACAGCC CAGATCCTCA GCTCTCCAAT GACA1TPCC TCCACTAGAC TTGAGCTACC TCCTTCCCTA GGCACAGCCT CAACCTCGAC AACACCTAAG ACTGTACCGT CTCTAAAGTC ACATGTTCAA ACACTTCACT CTITAACCAC TGTCTCCTAT TCTTGCAAGT GTATTGCTCA AGTATCTCAT TGCAATGCTT TPTACTTCTA CCTCATITGAA CCTCCAGGCC ATI'AAACATI1 TCCTTATTTC TAACCATCAG G'1TTCTCCTT ACTrG'rrrGT TTrGThTA'T7 65 GTI1TC'Tfl 'TIT1YFTT TTTGAGACAG GGTCTCACTC TGTTGCCCAG GCTGGAGTGC AGTGGTATGA TCTCGGCTCA CTGCAGCCTC CATCTCCCTG G'ITCAAGTGA TTCTCATGTC TCAGCCTCCC GAGTAGCTGG WO 00/62736 PCT/US00/08020 71 GACTACAGGT GCATGCCACT ACGCCTGGCT AAGATITGT ATITATFA GAGAAGGGGT TTTGCCATGT TGGCCAAGCT GGTCTCGAAC TCCTAACCTC AGGTGATCCA CCTGCCTCAG CCTCCCAAAG TGCTGAGA'r ATAGGCATGA GCCACTATGC CCCACCTGGT TTCTCCTTAT TTATCAAG TCTATGCTGC ACTATTAAAA CTGCCTTGAC AAAAATTATA ATAGTGAGAA AATTATGACA GTGAAAGAGA TCTGAAATAA TCAACCCCCA 5 TCTTGCCT-IT ACC'FrCCAGA CTGCCCTTAA TAA'ITCCTGA GCTrGGGCCA AGCTATC IT GGCAGAAATT TAG'TIATAG TTTAAATGAT AATAGCCCTr CTCCAAAACT AAACTGCCTr TGTAAAACTA ATAAAAGACC ACCAATGAAA GGTTAGGAGG ATGAGAGGAG CCTGAATTCT GCTAAGGTGT AGATGTAAAC AATTACCAAC TGTrAT'rCCG GAGGTCACAA GATITGCAAC ATCGCCAATT ACTCCTGCAG ATAACAGCAC TATCATAGAA TCTGATTGGC CTITGAGAT GTCTT=CAG ATTCTTACAT TrCAACTGGT GGCTCTACCT GGACCCATCA 10 ACAAGTCCTG TGGCTCCACC CAGAAGCAGA CTTAACATGC ACAAGGACCA TITTCCACAC CGCTATGATT GCATCCCAAC CAATCAGCAG CAACCATI'CC TCTGCCTGCC AAATT1ATCCT TGAAAAATCT TAGCCTTAGA ATTmTGGGGG AGGCTGATTT CAGTAATAAC AAAACCCCGG TCTCCCATTT GGCTGGCTCT GCATGAATTA AATrCTTTCT CTA'I17GCAGT TCCCATCTTG ATAAATCACC MLIATCTGGG CAGCAAACAA AAGGAACCCA TTGGACAGTT ACACTGT-rGG CAGATATATC TTGCTrCCAA AATTGGATTT TTGTTTAATG AATI17ATTCT 15 GTITTCTTGA TAMTACAAC TGTGAATGrr GTGTCTGAAT TCTCTTTATT TCrrGTrGAA AAGAACTATA TTGCTACAGC CAGTACATAC AGATGGATAG CTAATrACTC AACACGGGGG GATGTGACCA TCACCGCACT GTGCAAATGA ATGTTACCCA TYrGTCCACTTr TTCCCAAACT ACATAGTGTT ATATGGTATA TGACCCAATC AACGGTGGCA AAGCTCCAGA AATACCACAT AGACATCAGG GACACTrTAA ACTAATCAGC CTATAGTCCT T=CAGTAA TI7CCAAACC TGGTrGTGCA TCCAAATCAC TTGGTAACAT TAAAAAAACA AAAAAATATA 20 CACGCAACAT TCGCTCCCAA TCCTACTGAA TCAGAATATI' TTGGGTTGGT TCAGGAACAT TCAGGAGYI1? TTCAGGGTCC AAGGTI17ATA TAATITGAGG TCTCTC'TfTG AGAAAAGGAA CGTAAAAGCG TCTTGC1TY ATAGATCYTA CAAAGATGTA TTACCATGTA AACACATTCC TAGGACCCAG GCCCTTGTAA TTTAAAGGTIT TATCTAAGTA ATGGGCCCTG AAGCTFAATT TTCA ITATCT TCAGGGCAAA TTACCTGTGG GY7AGGG=T AGGAATATAT CTCTCTGTGT ATGTGTGTGC ACATTAGGAT GTACGCT-FGT GTGGA'Trr TfTVFFT 25 'TFTTT rC TGAGACAGAG TCTCGCTCTG TCGCCAGGCT GGAGTGCAGT GGCGTGATCT CTGCTCACTG CAAACTCCGC CTCCCAGGCT CAAGCGATTC TTCTGCCTCA GCCTCT7GAG TAGCTGGGAC TATAGGCACG CACCACTATG CCCAGCTAAT TTTTGTAYI17 TTAGTAGAGT TGGGGTTTCG CCATGTTGGC CAGGATGGTC 'ITGATCTCTTI GACCTCGTGA TCCACCCGCC TCCACCTCCC AAAGTGCTGG GATTACAGGC GTGAGTCACC ATGCCCAGCA CTTGTGTGGA TGTI-TAAGC TCCCAGGTGA GTGAATACAA AACTAGATCT TTCCCTTCTG 30 TAGCATCTGT ACTGMIIACT CTATGCATCT CAATATIT TCTITAGTA TCTTrCC'T TTCTCTC FTA 'rrACTrCCTC 'PTGTGCTATr 'rrTACACCTC C71TITAAA AAA'TTTC CCTITTA'IT CTATI'GACCT T7AGCCCTCA CAATGA'I1CC TACAAGCCCC A'IMCTGTAA ATGGGGATTG AAATAATTGC TGGACTTG AGAGATAGAT ATATT1AAATT GCAAACTGGC AGTAGTGGGG GCAGTTGATA CATAACTAGG TTTTAAAGTC TAGCCTTCTG AGACCACTCA 'PTCCATTTGT GAAAAGTGAT TCTAC'FFC'r AYFATGAGCC AAAATATGCA 35 TTCATTCACC CATGCATTGA TTTATTCATT CAATAAATAT TTGTTGGATG TCCACTCTGT ATCAGGAATG TGCTAGGTTC TGGGAATACA GCAATGAACA AGGTAATIT TCCCTACCCC TAAGGAACTT AGAGTTrAGT GGGGAAGACA GACATTAAAC AAACAATTGT GCAAGTAATA ATCTATAATT ATATTACA ATTAAAGGAA GGAAGAGACA TATGGA117AT GAGGGCATTA AAGAGGAGAC CTAGTGTAAG TAGCCAGTL1C TCGTGAAGGG ACATGTATTA GTI7GGAGUC TCCAGAGAAA CAGAACCAAT GGTGTGTGTG TGTGTGTGTG CGTGTGTGCG 40 TGTGTGTGTT GGGGTGTGGG GGTGTGGTAT TJTI1ATAGA AATTGTCTCA CACAATTATG GAAGCTGAGA AGTCCCATGG CCTGCTGTCT ACGAGCTGAG AACCAGGAAA GCCAGTGGAA TACTTCAAAG TCCAAAGGCC CTGGAACCAA GAGTGCCAGT GTI7GGAAGGC AGGAGAAGAT GGGTGTCCCA GCTTAAAAAG ACAGTGAAT7 CACTCTTIT GCTCTACATA GGGCCTCAAT GGGTTGGATC ATGGCCACCC ACAI17GGTGA AGGCAATCCT CTI7AGTCTAC CAATTAAATA CTAATCTCTTr TGGAAATACT CTCACAGACA CACTGAGAAA TAATGTITA 45 TCAGGGTGAT AGAAATCTTC TGGAGTT1AAA CAATGGTGAT AGCTGTACAA TCACATACAT FTTAAAGGG TGCGFITTAT GGAAAGTGAG TTTTATCTAA ATAAAATI1'C TAAGAAAGAG ACTTAACACA GAGATAAACA TAAGCACATT TA'TrGTCAAC C'TATAGTG TTATGTCAAA TAGGTCTGAC ATAAGCTTAA ATAAATATAT ACt=AAAAA TTATAAAATA TI'AAGTTA TAATTI'AAAA TTCTCAATAA AACTCAAACA CAAACCACAC TGGTAT'rTCA CACAGCTAAT TTCTAATGCA G'TrTACATAA ATATACAA CAC31?AAACA A'ITCAAAGA 50 AAATAACACT GTA ITCCATA CATAGCCTGA TCACAGTAGT TGTTCTCTCT TATTTCCCAG AGT1TrCTG CCCC'ITTAAA AGAACCTCTG CTGTTCTGAT CCTTATCACA TCTCTG'II GACTGTTGGC TrG'TGTrG CCAGTGTJ'CA GCCAGAACTT CTCTGAAACT TITTCAA CACATGCTAA G7rAATGGAA GTGTAGGAGA GTTGATTC TCACACTCCT CAAGGCTAGA GCAGC'I=GG CAA1TACTGA CTGAGAATI' TTCAT[GCCA GTGATCAACT GAAAACTGGA GATTCCTh7FG GAATTGTTAA ATCTGCTTAT AAATAAACAT AAATGCTTGC 55 TCACACAGGC ATTCCTCTCT TCCAGAGCAC CCTAACATAC AGAAGAAAAC AAATAGGGAA TAACTATTAG ACATCT7CAT TCGTTAAAAA TCTACCAGAT GACTC'T-rA CATGGTGAGT TTCTA'ITGTG AATTT1AAAAT CTITCCATAAT ATACAAGAAT TATGMIIACA TATCATATCT GACAAACATC ITTGTAGGAA TGCAAAGCAC ATCCATCTI1? CTGTATTCTT TTCCAACAAA GACATTCATA AAATTATACC TTrGTGTG Fr TGCATrTATG CTFJTATTFAG 'ITCAAAACGT TTGGCCTCAT GGAAG7II= CATCGTGGAA ACCACATAI1 TCTGAAAAAA 60 TATCTGACAA TATACAAACC 'PTCCATTCAG TIT1ACTCT CCAATTCTAC CATGTTCA AAAAACAACT GTAGTAAAAA CACTCAGAAC LTTA'FrCTGG TT1AACATCAT GCC'I1GCTAG GGGACAATAG YFTCCCT=f TGAAATAAAT TTFAAAACAGA TGTAACATAA 'TrTGrAATA AACAATGAGG GGGTAATCTA GAATAAGTAA CTTTTACCAT ATCATAGTL'G ACAGCATTTA CAAGTT1T AAGTCCCTAC CACACTTGTA TI'GAATGAAG AAGTATGGAA GATTATAATA TATTCAATGC AAGTAAAAAT ATCACAATCC T7AAGAACTC TTTAAGAAGC 65 ACTGAATCCC ATAGGGATGA AAGTGA TTAA AT[GTGCATA GTAACCCTCG CACAGAGCAT TCAGTAGGAT TTGCACCATT AACAACCCTC CATGCAMG CCTGTGGGCA TTCAACATCT GTCATVIT TAAGTTATAA WO 00/62736 PCT/USOO/08020 72 TATTTTAGT CATTTTC CTCTAAACTC TGGATAATTA TTATTCATTC TTATGACAGC AACTGTGTAA TCAGCTGTCG AAACACTGTG AAGGGCAAAA GAAAGAAAGC CACAAAATAT TGTGTTTCTG TGCCAAGATT TTACAGCGAG CAAGGGAGAG TTAGAAAAGG AATTCTGAGA TTTCAGAGTC TTGGTCTCTT CACCTTTGCT TGGAAGAAAA TATCCTTTCC CTTCATTAGC CAACACTTTC TTGATCCTGA GAGTAGGAAA GGGAACACTG 5 AGTCTTTTCA GTTGAAGGCC GTCCTTGCCT GCTGGACTTT GATCTATTGA AGTGGTGATG GGTGTTGCGG TTTCAGCCAT AAAGGCATCT GGCATAGTAG GCAAGAAGGG CCAGAGACCC GAGGAGAGTT ATCTGTCTCT GTTAACTTCA GTGTATCCCT CTAGTTCCCC AGATGCACCT GTTCTGTAA ATATAAACAT GCATGTCATC AGAACACTTA ATATTCTGCA TACTGATCAT GACAACAAAA TGTACCTTCT AACACAGACA CTCTCACTAG GATAGACCAT GTAGGAACAT CGAATTCTAT TCAGTTAGGA CAGTGATGAT GTCTACATAT TATACCTCTG 10 TCAAAACCTA CAGAATATAC AACACAGCAC AGAGTGAATT CTAATGTAGC CTGTGGACAT TAATGAATAA TAATGTATCA ATATTGGCCC ATCAGTTGTA ACACTAATAT AAGATGTrAA TAACAGGGGG AATTGAAGGG GTGGTGGGGA GATATGTTGG AACTCTTTGT GCTTTCTGCT CAATTTTTCT GTAAACTTAA AACCGCACAC ACAAAAAAAG TTATTAAT TTTAAAAA GTATTCAGAG GGACTTGACC TCCAAATT CTCTCAAAGC AGGTCGGAGT AGTTAAGAAC ACAAATTA GAACCAGACT GCCAGAGTTT GAATCCTGGC TACACCACTT 15 ACTAGCTTTG AGATTTCAGA CAATTTACTF AACTTCTCTG TCTCATTTTC TTICATCTGTG TGATAAGAAA TAAAGTAACA GGCCAGGCCC AGTGGCTCAC GCCTGTAATC CCAGCACTTT GAGAGGCCAA GGCGGGTGGA TCAGGAGTTC AAGATCAGCC TGGCCAACAT GACGAAAAAA TACAAAATCT CTACTAAAAA TACAAAAATT AGCTGGGTGT GGTGGCAGGC ACCTGTAATC CCAGCTACTC AGGAGGCTGA GGCAGGAGAA TTGCTTGAAC GCAGGAGGTG GAGGTTGCAG TGAGCCAAGA TCATGCCACT GCACTCCAGT CTAGGCAACA GAATGAGACT 20 CCATCTCAAA ATTAAAAAAA AAAAAAGTAA AAAGAAAAGA TAAGAAATAT AGTACCAGCC CCTATCTCAG AGT7CCTAGC TTAGAAAAAT TCCCAGAATA TAATAAGTGC AATGTAAGGG TCAGCTATCT TCATTATTAT TATCTATCAT AAATGAAATT ACACAATAAA GCTAGATCCG TTTCTTTCCT CTCCTTCTAC AAAAAATAAA GCAACTTTCC AGAACAATAC CCAGGTGATG ATTTCTCCCC TGCTCCCTCC CTAAGATATr GGCAAGTTTG GAGGGTTCAA GGAGAAACAG AGCATGTAGA GAAGATACCT CTCTCATAAC CATTTGTGAT TTACAAGTCT 25 TACCTGATTC TTTTGAACTT AAAGGATGTA AGAAGGCTTT TGGTAGCTTC CATCTGATTC AAGGCTTTGG CAGCTGCTGT GGAATACATG AGAACACTAG GTAAAGCACT GTCTTCCAAC ATGAAGAGAG AAAAATATGT GGAATGTTCA ATGGCATGCT TTGTATAAGA ATGCAACTTA CCTGGCAGGA ACAAATTTCT TTGCTGCAAA AGAAAAGACA AACAACCATT AATTCAGACT AAATGACTT TAAGGATATA TTAAATCCAG ATACAATATG ACTTAATTCA TCAAGTGTTG CAAACTCGAT GCTTCAGGGC CTCTGTAATA ATCAGAGCAC AAGCATGGCT 30 CTGTGGCATC TAGGGTAAAA TGCAAAGTGC ACAGCCATCC AAAGGGCATA GCAGCTTCCT AATGCCAGCA AATAGCTACG GGGTCATCTT GCCCAATTCA GCTCCCAATT TTTCATGAGA AGTCCAAAGT CTTAATTTAA ATGTGAGATT TCCTATTTG TAAACGTCAG AACTTAACTC AAAAATGTTT TAAGTACTCT TAAACATGTA AGCCAAACAA ACCATGAGTG TAGTCAGATG TGCTTCCATA TTCCTTATGA GAGACTCTCA AATTTAAGCC TGTACTCCAA ATAAATCTCC TTAGGAAGAA TTTATCCAT TTTCCTTAGA GTGCTCATCA TGGCAGTTCC 35 ATTGCACAAT TCCGGGAGGC ATCATATAAT TCAACATGAA TAGCACCCCC TGGAGTTGTA CAATATTAGG CACGACTAAC ATTTTTATTT CCTGAAACAC TTCCCACACT GAGTTGTACT ACTAACTCTT TTCTTAATAC TTCTGCTTAA TTATACTGCA TTTTATCCAG ATTCTAATTA TTGTTTAAAT CAGTAAGCAA GACCATGACT TATCAATGAG AAAGAAATGT ATTCAAAA ACATTTGA AGTACATTCA TAAACTTCCT CACCTTTCCG TAAGCATTTC CGAAGCCAGA GGAGAAATGG TGCTAATGTC AGGAGGGAGA GTCCAGCAGC AGAAAGTCCA 40 GCTACCAAGG GAATGTTGGA CTCAGTGGGA GCTAAGGAAG TAAGAGACGA AGAAAGGTCA TGAGGAAGAA TTGATGTTAA AGTCTCTCCG TCCTGTCCCT TTGGCCTTT TTCTGTACAT TCATTACTAG GAGCAGAAGA GCTATCTAGT TTAATACAAG AAGCAGAGAT GTGGCATTAC AGGCCTTTGA GATCTGCTCC AAGCCACCTT TGAAGCTATT TCCACCATTG GCAGGCAGAA CTCTAACTTG CCAAGCTCGT TCACAATACC ACACCACACC TTGGTTAATA AACACTGCAC TTGC7GCTC TCTTGCTCTC ACTCCCTCTT GTMCCATT TCCCCTTTCT 45 CCTCTCCTCT CTCTGTCTCC TTTTCCAGT TGTCAGAATT CTACCCTTTC CATCAACATG CAACTTCTGT TTTCTCTA TCCCCATACA ACTTAATATT CACAACTTGT CAACCTGGGC GAACTTTCTG GTTTGGATAT AATGAATAGT TGATTACTGT AACAAGATAG CTCCCCCTT7 TTCTTTTTAA TCACCAGACA ACCACCATCA ATCAATGCAT CACCTTCACA GGTAGGTAGC AGGCCAGACC AGTGTCCTGT GGCTCCACAT GTCCGAGCTG CAGAGCCATT GAGCGTCCAT CCTTCAGGAC AGGCGAACTT GCACACAGTG CCAAACACGG GCTCCCCACT 50 GCAGCTCATG TTGATCTTTC CCGGAACTGC CAGGCTTGAA CATTACCA CTGCAAATGT TAGGTACACA GGCAGAGTTT CAGAAAAATC TACTGGAAAA CTTCCAAAAC TTGCTTAAAA GTCAACAATG AATGTAAAGT GTAAGCGCTA CTTAGTTTC AGCATGTAGG AAATTAGGAC CAAACCCCTT TGGGGCAATC TAGGTTCAGA AACTTTATGA AGTATTTGAC CTGTACCCTA AAAAAGTCTG CACTCAATTC TACCTTGGCA GGAAGGAACC TCTTCTGTCC ATTGTCCCTG AGATGTGCAC TCAAGTTGAG TTGATCCATG TAATTCAAAT CCCTCCTCAC 55 AGCTGAAGGC ACAAGAGGAC TTGTAGGTGA ATTCTCCAAT AGGGGAATGA GCACACCTCA CCAAACCCTT CGGGGGCTGG TGGACAGCAT CGCATCTCAC AGCTGGAACA CACGAGAGAG CACTTTAGAA GTTTGTTTGC ATCTCCAGCA ATACGTTCC CAAGGTAACC AAGTTCCCAA GCTCTTCAAT AGTTCTTT ATCTTAAAAT AAAATAAAAA CAAAGACTGT ACCTTCACAT GTGGGCTTCT CGTTGTCCCA CTCCCCTGTG GGGCCACATT GGAGCCTTTT GGATCCCTTC AACACAAAAC CCTGCTCACA GGAGAACTCA CAGCTGGACC CATAACGGAA 60 ACTGCCAGAA GCACTAGGAA GACAATTCAT GTAGCCTCGC TCGGGGTTGG ACAAGGCTGT GCACTGGAAA GCTGAGACAT CAAAATGATG GTCAGAAAAT ATTGCAGTGG AACTAGAGAG TACTTGGCGT TTGTTGAGTG AACCCAGTTC ATTCAAGCAA CACTTGGAGA ACTGAAGATT CTTTATAATT CCCTGGACAA ATGGGAAGAT GGCTGTGTTT TCTTTGAATT TCAGCCCCCT CACTGATCAT GGCACTAATT AAAAGACTAA TTAATCAGAA CATT1AGTrCC TGAGCACTGT TCTTCTAACA CACAAAATAA ATTATGGTCC AAGGAAAGAT TTCACGCAGT 65 CTGAGGACAA CATATGGGTC ATGGATGTTr ATAGATGGTG CCAAAAAGAA AGAAAAGAAA GCACCCCTAT AAAATTTGTC TGTTTTGCAG TTTGGTTTTT GTGTTATGTT TTGCTACTGG AAATCATTCT GTGCTGGCTT WO 00/62736 PCT/USOO/08020 73 TGGCTAGGAC AAGGCCAGTG CCTGATAGTA AAAACTGC'IT GTTrrCAATA TCCTTGCTCT CAC'ITAAAG TGAATTAAAA =rACTGCTT ATATATGCAT CAATACTATC TCTGTAGCTG ACACCATGCT TGAAACAGTC TCATCACTGC TAATTATGAG CCA'1TTCAGA AGACAGGTGT GATGAGAGTT T17ACATTCAA ATCATGTTCT CATT1A117CTG CTICCGAAT 'TrCTAATAT GA'ITCC'TrA GATTAAGAAT TCTGTCTATT CCATGCTAAT 5 GTCTACAAAG TITTATCAGC ACATCACAGT TAAAAAAAAA CAGCAAAGAA rrCATTCITA ACACATATGA TCCTITCCCT GGCCAAACAT TAGTrCTIT AAATGAATCT CAAAGATACG AGGG'FrGCTC ATCAAATCTG ATTTCTATAG TrrAAAGTGGG TATFTGGTI TLTITCACT GTCCAAGTT GAAGATGGTT GTrCITTAAG AAAGTATAAA TCGAAGGATC TCAAGCTT1AC CTTCACAAAC TGGGA = GC TGTGTCCACT GCCCTTGAGT GGTGCATTCA ACCTGGGCTG GTCCCTGCAA CATGAAGCCT TCCTCACAGG TGAAGTTGCA GGATGATTTG 10 AAGGTGAACT CTCCAGCAGG GGAATGGCTG CACCTCACAG AGCCATT1CTG AGGCTGGCGG ACGGCCCTGC ATGTCACAGC TGTAACAAAT ATACGCATTG ATATTAGCAC GGCCTAGAAT TAGCTTGCCC ATTTCCAGTA TGGGTTGAGA GAAAGAATGT TCACAGTAAG TCTCCATGTG GAACAACTCT ACCTTT1ACAC GTTGGCTTCT CGTTGTCCCA ATTCCCAGAT GAGGTACACT GAAGGCTCTG GGCTCCCATIF AG'I1CAAATC CTTCTTCACA GTCAAATGTA CAGGTTGTGT TCCATGGGAA GCTTCCAGGG 'T=rGGAAAC ATTCCACGAA CCCATTGGCT 15 GGATTTGTCA CAGCATCACA CTCAACCACT GAGGATITIA AAGAGCACCA TGAAT1TAC AGAAGAATGA TCTmT7CACT TCCTATTGAG CTGGGTGCCT AACAGAGTGA GGAAGCTGCC TTCAAAGGGT AGATCCCAAA GTCCTATGTC AATTCTT1AGG GACATGCACA GCCAGAATAA AAGC1TIAT TCTITTCAT GGATATTCTA TCrr'ITCTGA TI17CCAC3TT GCCTATGCTG AGTGGTCTCT AATCTATG IT ATCATTTACG TGAGGTAAAA A'TfAAAAAA AATAGATI1CC AGA'ITAGGAG TrATGACTAG TACTGACATA CGTAGGCTAT TCATrTATTT 20 TAGCCCATCA GAGCCTGAAG AACTGA'F= TCTTIrG GCCTCTGGYr CAGAAAGATA AAATTAAGAG AGAAAAAGAG ATACTAAGAC TGCFI7GACTA TCATGGTCTT AAGTTAGTCC CATGGC FTGG AAAAGTTAAA CAGGGAAACA AGATGAGAAA TCCATTGAGA ITCTAGAGC TTTATTGIT TATGGTCTCC CTITACAAATC ACCAGAGCCT CAGAAACACC CATTTCAAGC ATAGAATAAA AAAACCTCTC TCAACCCAAG CAGGTACTGG G'I1GGCAATA TACATTGGCT GAGAGAACAA ATT1GTATrAA AAACAAAAAC AAAAAAAAAA CTI7TCCCTGA 25 AGTTTTGAAA ATGTAAG'PTG AATCAAAAAA CAGAAGCAAT GAGGGATGAG TTACAGAACG TTCTGTGCAT TCTCAGAGGG NITACCATT GCAGGCTGGA ATAGGAGGAC TCCA'ITCTCC AGAGGACATA CACTGCATGG TCTCCATGCT GCTTGGCAGG TAACCCCTAT CACAGCTGAT AGAGCAGGAA GAATITGTAGC TGAAGTITCC CAGTGGGTGA CTGCAAACCA GGCTTCCATG CTCAGGGGAT TCCAGGGCTG TACAGYTCAC! AACTGAAAAA GAAACCCAAA TCAGTTCTGC TCATCTCTCA CC'HTAACA.G ATAAGAACAC TGGAAACTAG AACTACAGTT1 30 TGG1TITYP TITTrAGT TTAAAAATT ATAAAAMTC TAATGGAA'Pr TGTAAAATTG ACTGTAATFC TACCCCTTTT CTm1AT-FCA AGAAAATGCT GATCCATAAC AACAACAACA AAAAAGCAGT GATGACAACC ATAAAAAAGA AATATI7GAGT GATATGGGGA GAGTAGTGTA ATrGTGITrA CCTCAAAACT GTTCAAATTA TATGAACAAA CACAGCAAAC TTAGGTACCA CAACAAMT= CT7T'FAC' TrCTCACAAC TGCTAAAAAT ACTACAGTAA GCTTCCAACC AGGATGAGAA CCATTCACAA AGCTATA'TrT CAAA'JTTAAG TACTAGAATA 35 CA'117ACAAAT I=AAAACCC TAATGCTGCA CTGTCTACTA TAGTAGCCAC TATCTGTGTG GCTACTCAAA Th17AAACTTG AATTCGTTGA AATCAAATAA CATTTAAAAT TCAGTTCCTC AGTGTCACCA GCCACATTTC AAGTACTCAA TAACCACATG TGGCTCATAG GTACACACTG GAAAACACAG CTATGGAACA 'TrCCATTAT CACAAAAGCT CTACTGCACA ACGCTGTGCT AAGGAATCTTN GGAGAGAAGC TCATCTAACT CTCTTAATGT ACAAATTTAG GAACTGAGAC CTCNT~CAT TCAAGTGACT TGCTCCATGC TACACGGCTA GTCATrACAG 40 AGCCAGAGGC CAGAGCATGA ACCAAGATAC CCTGGACTCT GTAACTCACT CAT=TCTACT GCAACGTCTT GTTACCACCT AGATGAGGTG AGTACATGTT CCTCGCAGGG ACACAGAA IT ACAGTTATT1 GAATGTGTCC TGTGTGCCAG GCACCATGTA ACCATGAGCC TATGAAGTTC ACACTA'ITAT TATCCTCATr TTACAATGAG AAAACTGACA TAGAGAGTTA AACTATCTTG TCAAGGTGCC AAAATAAATA AcTGGTGAAT CTAGGACTCA AACCCAGCAG GGTCTGACTT CATAGTCTCA GCTCACGATC ACCATATGAC ACCATCTGCA CCAGGGAAGG 45 GAAGGCATGC AGACCTGACT CTAATGCCAG CTAGGACGTG AGATGGTGCT ACCATCTCAA GTGAAGAAAG AGGCAAGAAC CAGACTTACT 'FrGCTCACAC TTGAGTCCAC TGAAGCCAGG GTCACACTTG CAAGTGTAAT TATTGATGGT CTCTACACAT TCACCGTGGC CACTGCAGGA TGTATTGGTA CAGGCAGCTA CGGAAAATAC AAAGCATGAT GAGGAGGACT A'ITACTGTGC TTATACTGAG TGCCTITGAT TrrAGAATCA ACAGTGTGCA ACAGAGACAT CAGCAGTCCT ACAGAGTGCC ATAGACTTA ACTGAAGTGT TIACAAAGT TCCAAATCTG 50 AGTTCAGGC CCACCTATCC TAAACCTlGA TGCTAATGTA TAGCTGTGGC TGGCACCTAC! CGTAGAAAAT TTAC117CTTC ACAAACTCTG AAGACAGTTC CCCTACCACA AATAAACAAG TAATTAAAAT ATGTATTGTG TGTGTGCA.TT 'TrATATGTA AAGAACTACA TA ITTGCCTA CAGTATTTAT ATATATTA TATATATACA TACACACATA TATGTGTGTA TATGTGTGTA TGTATATATA TAAAATGTAT ATAAATGCTG TAGGCTATAT ATATATACAC ACACACATAT ATGTGTGTGT GTATATATGT GTGTGTGTGT ATATATATAC ATATCCACAT 55 ATTCPI7GCCC ACATTCACAC AAAACAGCAA AAGAGAGAAA CTTTAGCAGT TAAACAGAAT CTfl1GGAAC ATAAAATGAC CACAATAGAG AGCAGTfIT GCATGCTGTA AATI17GCCAA. GATGCCCACA CACTGAAACT ACCTCCCACT GCTGCCGCAA ACTCCCTACC TGTGTAGCAT AGGGCAAGCT TCTTCTTGCT GCACCTCTCA TCATTCCACA TGCCCACATC TITCTCTC TTGATGTAGA TCTCCACGCA GTCCTCATCT TITTGCCTAT TGTTGGG FfC ACCTGGAGCC CAGTrC'ITGG CTrCTTCTGT CAGAGGMTC TGGGTCCTA CCCAGACCCA 60 CACATTGTTrG AcT-rITCTGA TTCCAATCCA GTAATAACFJ? GGTGAATAGC TCAATATGGA GTTTAGGTAC TCAATCTCTTf CTTTG=TG AA'L1GCAACC AGGTGTGTGT ACCTT7GCTG ACAATAAGCA CTGGCCTCAT CATAAGTCAT AGC~rCCGTG GAGGTGTT1GT AAGACCAGGC TCCACTCTCT TTAATGAGAA GCACTAGTGG GAGAAAAAGA AAAGAAATGG TAGAGTTTGG TACTGTTGTG GTI1AACTCT GACAACTGTG C'TITT~G TCTTA'TITT GGCAATG'LTT GTGACATGGC CCAGAC'Ir CTCATCTIT CAAAAGTAAG AAGTACGTAT 65 GAAGAAACAG CGACTTATTG 'TTFATCTCT7 11GTGACTGC CACCCACTAG GTAccTTrATC CACACTCACT CACAACATTA TAGTATACCC ATTTTGTAGT AGAATAATAA TCAGAATAAC TAAGC'TrAT TGAGCACT-rA WO 00/62736 PCT/USOO/08020 74 GTATGCACCA AGAAGCACTG TATGAGGTAC 'TrCCATGAA CCATGCTA~r GAATCCTCAC AATGCATCTG GGAAATAGGT CATTATGATC CACACTTTAC ACTTAAGGAA AGGGAGACAC CAAGAGGTAA AGTAAATGAC CCCAAGCCCA GGGAAGAACA CATrGCAGGT AGAGGTCAAG GATGCTGCCA GATATCCTGT GCAGGACAGC CCCAGACAAG CAAGGATATT TCAGTCTGAA ATATCTATAG TGCGAGAATG AGAAATC'rrG GTCTAATGGC 5 ACTGACTTAC CCAAAGTGAG AGCTGAGAGA AACTGTGAAG CAATCATGAC TrCAAGAGTr CTTICACCC AAAGGTTTAG GCTTGAAATA C~rCCTGGG GAGATAAAAC ACAAAATGAA ITAAAGAAGG AAATCGTGGG TAGCTAGTTA CATTATTCTA CCATGATGTT1 TAAGGCAGCA TCCTAAGA'I7 3TGGGCAAAG GACACTAGTG CAATAATCTT TATTrCAGAG TTTAATCAAA TAAATAAACA AA'TITAAGA C ITCAT[AT TTAGGTCAAA GAGAAAAGAC AGGTTAGC TACAATACAA TAAGAGCTTG TACAGATGTG GTTATrA GAAGGCCTIT 10 TGCATATCTG TGT117CATGG CCCGAGGCTG CC=TATAAA GCGTTCTGCA CTTACCG'IT TGGGAAGCAG TT-GTrCAAAC ACAGGATCTC TCAGGTGGGT ATCACTGCTG CCTCTGTCTC AGGTCAGTAT AGGAGT=G ATGTGAAGTC AGCCAAGAAC AGCTGAACAC TACTTCGGCT GAGGCCC Tr TATAGGAGGG ATTGCTTCCT GTGAATAATA GGAGGATATT GTCCACATCC AGTAAAGAGG AAATCCCCAA TGGCATCCAA AAACTJTCCC GGGAATATCC ACGATGCTTA AAATITACAAT GATGTCAGAA ACTCTGTCTC TrGAAGCTAC TTCACCT'frG 15 TCCATGCCTT TATATCGTAT ATGCAATITr AThAATATGA CAAAAATGCA TGATITTTAA TTATAATAAC ATAAAGTCTA TGTCTI17AAA AAGTT1GTAAA ACMIGCTG TTAGTAGTGT CTCTCATGTA GTTGTGGTAG TAATTAGAAT 'I1CAGAAACA GAAGGAAACC AAGAATAGGT TTGTCATCCA TAGTCTACTA CCTTCAATT CTCATTCATA GCTGTGGATA ACCAATCACT ACTCATTI TCTTrCr TCACCTGCCA ATTCAACATA TTTAACATGC ACTGTCTCAC AGAGGAATGA CTCACAAGGT AGATATTAAT CTTCAGATTT TGCACGGCAG 20 TTATGCCTAA ATTAAAATAT TATCTAAAAA TAATATCTAA CACTCAAATG GTTAAAATAA TGCCTTA'rrr TAAAAAAAGA AAAATGGGAA ATAGATATIT ACATCTGGGA AAGTTTCATG GTTTGTTCAG TGAAAAAAAT AAAAAGGAGG CCAGGCACAG TGGCTCACGC CTGTAATCCC ACCACTI1TGG GAGGCCGAGG CAGGCGGATC ACCTGAGGCC GGGAGTT1CAA GACCAGCCTG ACCAACATGG AGAAACGCCA TCTCTACTAA AAATACAAAA TTAGCTGGGC ATGGTGGCGC ATGCCTGTAA TCCCAGCTAC TCGGGAGGCT GAGOCAGGAG AATCGCTTGA 25 ACCCGGGAAG TGGAGGTTGC AGTGAGCCAA GATCACGCCA GTGCACTCCA GCCTGGGAAA CGAGTGAAAC TCTGTCTTAA AAAAAAAAAA AAAAAAAGAA AAGAAAAGAA AAAAAATAAA ACGGAAAACT ATATATATAT A1TTAATI1GG TCAAAAt1T GTTJ7AAAATT TPGAAATGT TAATGTGCAA AGAATAAAAA 'rTCYFrCCACA ATG FTAACAG TGACTAACTC TGGATGGCAG GA'ITrGGGAT AA'TTn7ATA TCCTrCATTA TTATF1TCAG GATITAAAG fTT=CAA TITCCC'Th7 'FCACCTIT ATAGTAACAA GAATACAGT-r TAAAGAAACT 30 TGTCTCTAGG CCAGGCATGA TGGCTCATGC CTGTAATCCC AGCACTTTGG GAGGCTGAGG TGGGTGGATC ACCTGAGGTC AGGAGTTCCA GACCAGCGTG GCCAATATGG TGAAACCCTG TCTCTACTAA AAATACAAAA ATTFAGCCGGG GTGTAGTGGC GCATGCCTGT AATCCCAGCT ACTGGGGAGC CTGATGCAAG AGAATCGCTT GAACCCAGGA GGCAGAGGTT GCAGTGAGCT GAAATCACAC CATTGCACTC CAGCCTGGGC GACAGAGCAA GACTCCATCT CAAAAAAAAA GAAAAAAAGA AAAAGAAAAG AAAAGAAATI' TG=~CCAAA TGCAACAGAA 35 GGAGATGTAT GTGGTATCCT ATATTCCTGC TCTrCATIT GACA'rrrCT- CTGGGTGATT GTATACAT~rC CCCATCTCTG CATC'I1ACCC TATCTAAATG ATGGTAACAG TAAATGGGGA TCATITTAAT TTrCCATATTC TGTAGGT=T CAGAGCTCAA GTCAAGCTAA TATJ7CTATAT CTACAGCCTr TCAAAATAGG AGGTCTATCT AAAAATGTAC TGTCAGCAGA CCTGAACGAG TAGTGGTAAA AGCCTCGTTT TFCTCTTTAC TTGTTAGCAC TGGTCTrTCT GTGTTCATAA AGATGTCAAG ACCCAAAAAA AAAACAAGAA AAGAGAAGAA AAA'rrCCAAA 40 AAAGACAACT GATTAGAAAA AAATAAC FTA ATrAACGAAT TTAATTICAAC CCCTATCAAA AAGCATAGAA TTATTCCCT CCACCTrACC ACTCTCTTAC ATGATCCAGA TACTGACATT A'PTCCAATTC ITTATCCCAC '1TTACTrAGC TCAATGTGGT TGTTGCTTCA ATAAATTCAG AAGAGTAATC ACTCATATAG TGTTATTTA GATTAGGG CAGAATGTCA AGTTGGGTTA ATACAYI'ATC TGTATGTATT T7A TTTAA TAAAGTATGA ATACATAATC TGCTATIT1 AAAAAGCATG GTCAAATGTA TAGAGTAGCC AAATCTTAAA AAACAA=hA 45 TCTTCGATAT CAATAAAGTA CCTAATAATT ATATTGCTAA TAGAAATTAG TCGTITAACAT CCCTAGATAA CTAACn7TAT TATTGCGAAT =IICATAAC TAAGTTATA G TTATCTCT TCCCC~fT= AAAATTAG Fr CAAAGATATC TAAAAATAGC CCCAGTGGTG ATGAAGTTTC TKITTTACTI7 ACATATATAT GTCCTGGACC CCCAATTATA ATCTCTAACA 'ITTATGAGT GCT-FACTATG TGCCAGGCCA TAYICTGAGC A TI1TGTATG TTCACCTATT GATTATTCAA TCCGTACAAC AGCCTATGAA ATAGGTACTC CTA I1'ATCCC CArTrACAG 50 ATGAGGAAAT TGAGAATCTG GGGATEITAT CTCATTCAAA AGCACAGAGC TAAGGGTI1GA AACCAGGCAG TTGATATCCA GAGCCCACTC CCTACCTGC TACTCCAAAC CATGATTCT 'TrTG'TGTrA TGCCCCGAGA 'FrCCTrGTTC TACCCAAGT[ TCCTGTACTC TTCTTGCCCT CTrC'FrCCTG AGACATCCTT GACCATCACA GCTCTCCACT GAGATAACTG TGTCCTGGGT TCTGAGACAT GGGGGCTGGA AGGGACCCCA GGGACAGTGA GCAGTAGGGA GAGGATGCAG TGAGAACAGA CCCTGGATCC CCGGTGCATA GGCAGGGAGA AAGTGGACAA 55 AGGAAAAAAC AAGCAAGGCA GGTGGAGCCA TGCCTAGGTA AAGTTGATCC CTAAGCCACA GTrCCCAGAA GT'TCCTGATT CAAAAGCAAA TTTTCTCTAA GGTCAAAGGG CAAACTGATT ATI'CTAAATT CTAAACTGAT TAITTCTAAA TTGAGAAAGC FTCAGGGAGA GATCCCAATA TTCGAAGGAT AAGAGAAATG AGGAGTGGAA GAGATAGGTG AGTAACAGTA ACT1TAAATGT AGACTATATA TAATATATAA TATATGTAGA GTATATATAT ATAA'ITACAA TATATTATAT ATGTGGAATA TATATATTAT TTATATATAT TTATATAMII TATATATATA 60 GATAYITIA TATTTTATAT ATAAATATAG ATATITMAT A11=ATATA TAAATATAGA TAThT=ATA TATATTATAT ATAAATATAT GTAAAATACT GTGAAAGAAG AATAGAATCT TGAGACCTCA AATTICACTAT GCCAAAGGGA AAGTI'AAGCT TGGGAAATGA GTCATGCAAA AACTGCCTTrC C1TrTTCC CAAATACCTG TAA'TTCACA TGC'FrACTT ATCTTATATA AAATGTAGAT GTACTGAGCA TGAGATCCAT GCATAATTC CCTCTAGTCC CTTC'TTrA CATGTAAAGT GTAGACTCAC TGAGTGTTAC AGAGCCT7GC CACAATGTAA 65 ACACTTGTCT CAYIGCCAAC CCATC'ITTCG 'ITTAT=CT TCCCCTCCTG CTTGCTC'rl CCCCTCTAAA GATGGAAG Fr CCCAAAACTC TCTTGGAAA AAGCGCAGGT CACAGATCCT ACAGTGATTT GTGTTTCTIT WO 00/62736 PCT/USOO/08020 75 TACCTGGGAC AAAATAAACC TCTAATCTGT TGAGATATGC 'ITCAGTrACT 'FTTGGTTTA CAATATGTAC ATGTATGTAT ATAA'ITTATA TGTATATAAT ATATGTACTT G11TAACCA GAGGTATGTr A I1CAAAATC CATTCATCCT TACAATT1ACC TGCATTCTCC CACAGTAT TCTGTGTCCC TGCCCCCGAG GTrGTCACTG CAAATCAGGT ACATGGATAC TGGGAGGTGA TGGGCTCCCC TCTGGCTACC TGGGCTGCTG AAGGGGCCAT 5 AGACAGACCC AGCTTTCCTC TCGTGGAGAG GCCCTGGGCC AGCGCTGCGT GGGAGTGGGA TI1ACAACCAG ACTATAGC'IT CTrCACCTGC 'TCCTAT. CAGGAT7CA TAAGAGGCAA 'FrGCTTGTr FITGAGGGTG GGGGCAAATC AGGGGGAGTI7 GAAGAGGAAA TTGGGTAAGA TTTGAATAGT TGGGCATGTT GAATATrATG AATATCATCT CCCTCTTCAA ATAATCCAAA ATATACCCCC AAGAAACAGG CTGATTAGAG GTGC'I1CAAG GCTCCACTGA ATCTCCCAAG CTCTGAAGAT GTAGCTAGCT GTTACCGGAT TGCCGGTrT CAAGCCTCGC 10 CTCACATGGA CCCTCTTGGC AG = ]CTCGC ATGGGGGAAG CATCCGCTAC ATAGATGGGA ATGAAAAGAG GAAAGAAGAC GGTGCAAACT CAGGCACACC CCGGTGTCTG CCACCAGTGC TATITAATCT CTGAGGTGTC ACCCTTCCTG GCT11TAT-GT CTCTTCCTGG AAGTCTCTIG TCCTCTCCTC CACACCCMT AATCAGGCAT CAAAGACT AACCAGTIT GCTGTGTGCC CAGGCCCACT CATTCTCACT 'TrATGGCAA AGGGAGTGGG AGACAGAGAG ATAGCCAGAA AGAAGAGAT[ GGGGACCCCA AGACAAATGT TAGAAT1TA ACCAAGGCCA 15 CCCTGTGGAC AGGAGATTAT TGGGTVrAGT GGAAAGCAGC ACTGGCCACA ACCACACGTG GCAAAAGCAT CTATCGAGGA GTGAAGYI7AT ATI1GGTGAA TGTGACCGGG AAGCAGGGGC AGTGGTGTCC TCCTGCCT7C CTGAGGCACT CTG T7CCCT ACCTCTGCGA AGGC'fATT TACCCCTGAG TGC'I1AGT TGAAAGCCTT AGTTCCCTCT CTCCCATAAA AAAGCTCTAC TCTGCTAACA TCTAAGTrAC CTGCAGAG TCTTAGGTAG AGGGAGGAAA TCCCAATAAA GATTCCACCC TATCTGCAAA ATACAAACAT GGTATL17CTT1 GCA'VrCCCAA 20 AATrGTGAAA GAAAATGTGT ATCACCACAG TAGAGAATGG CA'TTTGT TTGATCAAAA CCTAAATATA TTTGATGAAA ATGTGTCTGG TTCTAAGTTT ATrCCCAGA AAGCCATGUT TACTCACTTG GAAITATAG ACATCTTATA ATATCTGAGT CGAGTAGGAG CTCCGGGCTC TACCTCACTC TTTTCTCCCA CACCCAGGGG GAAGTGTAGG GTTCTCAGAC TI17AGAATAA AGAGGAATCA CCTGGACAAC TCACCTAAAA TGCACATCTT CAGGTCTCAT ACTCAGAGGC TCTGACTCAA CAGGTCTGGG TGGCGCCCAA GAA'ITTGGGC TTTAAATGAG 25 TATCTCAGAT GATTCTAATA CAGAATGTGT AAGATGACCA GATCCTATCA CACTrFAGATG TATI7GGCCTA GGGCCACCTA ACTTGGAGAA AATGTT1AGTA AGACCCCGTG GTTGGTGCTC AGCTATAGGT ACCAGAAThT TGATCAAAAT TTACTATCAT TGTGACACTT CTMTCGGAA CTGGAAGGCC AGAACCCCAC TTGTAAAGTG CTGGGAAAAT ACAAGGAAAA TTTAGGGTGA GTAGCA'TT GAATTCI7AC ACATGGAAAG TAAATGTATA AGAAT1'CTI'A CCAATAAAAA AAAAGCAAGA GAGAATAGCT GCTAAAGAAT TAACACAAAT ATGTATATAT 30 TAGTTAL17CT CTTTTCTCCT CTGATTCCAG AGGACTTTGT AA'rrCCACTA A'rrC'FCTrFG AGCTTCCAGG ATGATCTGAG AC'I1GAATI17 TTCATGTGCT T=IGCTTCC TA I=GGCAG CATCTI7ATCT TGAAGTPCC GCT'1TCTGCT TGGGGACCTA AAAACTAACT AATGGGAATJ' TCTTCAAAAT GAGCAAACTC TGGTGAATTC CCAAAGCGGA AGAAACAAGT GAGGATCGGG CTGGTTAATr AAGAGAACTT TTCCTGAATG TAGCCAGACT GTTTGCCGAC TGTTGTTAAC ATGAGGGAAG AAATACCCCT GGATTTAGA AGAGCCCCT7 GTrTGTTI17C 35 C'frGGCCATTr TGTGCTGCYI' GTITGTAAG TCAGAAA TT CCTGAAGGAC TATTATTAGC TTTI17CTCA CGTCAGAAAA C'TCTGCTCT GGCCACTITT AAACATATAA CTTGGATIT ACTGTAT7AG AAAATGTAAC AA'ITACAGAC AGCACTAAAA GGACACCAAA GGGCAAAGAA AATGGGTAAC TTrCT TCCCCAAATC TAAAATAGGT GATLTGGAG AAGTAGGAGA AAAACCTGGA =IICTAGAT CTCTI17AGAG CTCAACAACT GATATAGTrA ATTATGTAAG TC3TGATAT 'PTGGAAATGA TTGGATTAAC CGGATAACAA TGAATA'1TTA 40 AATACAGTGA TTTGGCCAGG AGCAGTGGCT CATGCCTGTA ATCCCAGCAT TTGGGGAGGC TGAGGCGGGT GGATCACCTA AGGCCGGGAG TTCCAGACCA GCCTGGCCAA CATGGTGAAA CCCCATCTCT ACTAAAAATA CAAAATTAGC CAGGCGTGGT GGTGCAAGAC TGTAATCCCA GCAACTCGGG AGGCTGAGGC AGGAGAATTrG CTTGAACCCG GGAGGCAGAG GTTGCAGTGA GCCAAGATCA CGCCATTGCA CTCCAGCCTG GGCAACAAGA GCGAAATTCC ATCTCAATAA ATAAATAAAT AAATACAGTG ATrTAACACA AGAGA'TTCT ATITCACACT 45 AATGAGCTCT GTCACTGGGG CAAGCTTC'T TGCCTCAT-rA AGTCTCAGAT TI7CCCGAGAG CTTA'TrATr TATACCAAGA GTGC ITTACT ACCGTCTCTG CTAGCTGTGA CATAATATGA CAAAAGGTAT AAATATGGGA AAAGGCACTA A ITATATCA AAGCGTTCTT CG'TI=CCT TGCTGTGAAG TITTTAGCTA ATAATTCATA AGAATATACC ATATE7AGAG TGTTTACTAT GCATGGGCCT GGCAC11FCAC ATACATTGCT TCTTACAAAT Th7ACAAAGT GAAAGGTAGA TA'ITAATCTC A'TJTATGGA GGACAAGATA GAGATCTGGA GAGGTTACAT 50 AACTTGCCAG TGTTITCA GTTAATAAAT GGTAGGGTGG AGATTCAATC TGTGTTACTC TAAAGTCCGT GTCC'TTTA 'ITGGCTCCAT GCCTACTCAG ATITAAATCT CAGCAGGGAA GTAAACCYTA GTTI=ACAT GAGAAAATGT TACAGCAGCC TCTCGGCTI' CCTrTACCCC CATCCCAGTT TCACGAGCTT1 AGTGCCTTAG ATCGGGTTCC TTTAGAAGCA GACCTCGAAA TAAGGATGTG GGTGCCAGTC A'TrATTGAA AAGATGATCC CAAGAAAGCC TAGTAGGAGA GTGAGGAAGT GAGATGGGGA AAGGAAGAAA CTCCACAAGA AGTGTGTTAA 55 TAAGCAGGTT ACCGCTGTGG GCAGCCATGG GGCTCAGCTG CACTAACAAA CTCTGTCTAG TACAGAAAAC CTCAGGGTCT CCCCAAGGAG GGGCAAGAAG TCTGCCTAGG GTATATATCC GCCAACTCAG TCACTGGCTG AGAGCTGATC CTGGGAGGGC ATGGTTAATT1 CCTCTGCACT 'I7CAAGTGGA 'I7CCTGTGGT CAGAAAAAGC CCTCTACAAT GAAI17CCAGA TGCTTGTNT TAAATCTGAC ATGATCTGAA TGCTGTGT7G GGACAGGGTG GGCGTTATTA G=TCTGTC ATTACTGTAA CAGATTACTA CAAACCTGAT GGCTGCAAAC AACACATATT1 60 TATTATGTCA TAG=hLGTGT GGGTCAGAAG TACAGGTTAG CTCAACTAGT TTICTCTGCTC TAGGTFTCAC ATTGCCAATA TCAAGGTGTC ATCCAGTTGG GCTCTTCTTG GGAGGCTI'GG GGATGAATCC ACFJTCAAGC TCATI'CAGAT TGTrGGCAGA ATCCAGTTCC TTGTGGTTGC AGGACCAAGG TCCCTGTITGC CTTGCTGGCT GTTGGCCAGG AGTCATTCTT AGCTTCTAGA GACTACCTGT ACTCTCTGAC TCGTGTCTCC ACTrCACCTT TCAAACCAGC AGCGGCTAGT CGAGTCCCTC TCTTCAAATG TCTCCAACTG TGCC117CACC TCA TrTCTCC 65 TCTGTGTACC ATGTCTGCCT CTACTGCTTG TAAGGGCTCA TGGGATTACA TTGGATTTAT TCAATCCAGG ATAATCTCCA TA'ITIAAGG CTAGCTGACT AGTGATCTTA AT7CCATCTA CAAAGTCCCT TCCAATAGTA WO 00/62736 PCT/USOO/08020 76 CTGTATTAGT CCATITTCAT GCTACTGATA AAGACATACC CAAGACTGGG CAATTCACAA AAGAAAGAGG TTAA'11AGA TTTACAGTTC CACATGGCTG GGGAAGCCTC ACAATCATGG CAGAAGTCAA GGAAGAGCAA GTCATGTCTT ACATAGATGG CAGCAGGCAA AGAGAGAGAG CTTGTGCAGG GAACTCCTCT FITTAAAACC ATCAGATCTC ATAATACTTA TTCACTATCA CAAGAACAGC ATGGGAAAGT CTTGCCCCCA TGATrCAATr 5 ACTCCCACCA GGTCCCTCCC ACAACATGCA GGAATTCAAG ATGAGATG TGTGGGGACA CAGCCAAACC ATATCAAGTA CCTAGATTCA TG ITTGATTA AACAACCAGG GAGCAGAAAT CTTCAGGAGT GGGGGGCATC TAGAATTC TGCCCACCAA GGCTGGGCGC GGTGGCTCAC ACCTGTAATC CCAGCAC'Tr GGGAGGCCAA GGTGGGTGGA TCATGAGGTC AAGAGATCGA GACCACCCTG GCCATGGTGA AACCCCATrT CTACTAAAAA TACAAAAATT AGCCAGGTAT GGTGGTGGGC ACCTGTAGTC CCAGCTACTC AGGAGGCTGA GGTAGGAGAA 10 TCACTTGAAC CCAGGAAGCG GAGGTGCAG TGAGCCAAGA TTGCGCCGCT GCACTCCAGC CTGGGAGACA GAGCAAGACT GTCTCAAAAA AAAAGAATTC TGCCCATCAT AGTAGGCTGT CCTACAGAGA CATAACCCAG GAATTAGGTG AATGGCTAAC CTAAATTAGC ACTGTGATGT GTITCTGAC ITFGGTCC2FrA TAGCTCCTCT GCTTAGATGT GGAACTAATC CATGAATGCA AGGGTTTGTC TAGAG=P~A AGTGGGAG1T AAATATCCAA AGTACAGGAG ATATTATGGG TGCCTCATCC ATGTCCCCTT GGCATIT7ATC 1TTCTTGGAT AACCCAACTC 15 TATTAGTTTT TATATCTCAC 'ITGTrCCTAT ACTCTGTGAA CTGATGTCCC ATAAATAGAC ATTTCA=IT GCCAGTCT7C ITGAACAATA ATTAGGATTA YI'AATCTAGC AGTTATCATT AAT-rGGCCAC TTCACAFAG ACACAGCACT TAGGACTTAA GAATACCATG TCATTTGATC ATCATAATAT GGTCAGGAAT TAAGTATTGC TATCCAAA317 TTACAAAGAA GGCACTGAGG GTrAGAGMr AAATAAC'JTG CTTAAGATGT CATAGCCTGT AAGTGACAAA ACTAGGACTC AAATACAGGT CCATCTGACT CCAAAGTCTA TGTTCTT1GGC TACCACACTG 20 CCTCTCCTAC AAGTGACCTG TGGTITACT ACTATATTCA CACTCTACTA ACTrACCAT CTCCCATGAG TCTGTCTAGA GGAGGGCACA CACAGCACAG AAAACACATG AATGCAAAAT AAGGAAGGGC CTACTTACTA CACAGAGCCA TT1CTAATACC TGATGTI7TGC TCTAATCCAG TITTACTATT AATTAGTTGC TGGTGCCCAA G'TT1TACTG AGAAATGGGG ATAATITGG AAGTCATAAT GATGCC'I1CT TCTCATAGGG TATITITATI17 G'rrGTrGTAT CTCCAGGCCC CAACACAGCC TGGCrI=AG TAAATGATCA AAAATACCTG 'ITGAATGAAT 25 AAATGGAGTC ACCTGAAACA TGT7AAACAT TTG L17CATGT GTCCTAATCG TGGATTTCAG GATAGTAAGC ATCCTAAAAG GAAAGCATGC ACACTGTI'CT TGCTACATI'A A TTrCTCACA ATATAAAAAA AGAAAAGCAT CTGAAAAAAG CTGCCAGCCG CTGTGTCTCC TAATATCAAA CTGAGCACAG ATATGGAGAA GCTAAGGGAG AGGGATGATG GGCCATGCCT CTAACCTCAT CATGGCAAAA GTCCTGGGGG TCAGACCCGA GGAGAGCAGG AAGTGTC'TTT TGAGGGATAC A'ITTCCACAG TGGAAATAAT GAGAC'rTAAA TAAATATTAT ATACACAG T 30 CAACTGTIT TATGTGTAAA GGTAGTAGGT TrCACAGTA AGGAAGCACT TCTTTT '1TTGTTTGAG ACAGAGTCTC GCTCTGTCTC CCAGCCTGGA GTACAGTGGT GCTATCTCGG CTCACTGCAA TCTCTGCCTC CTGGATFCAA GTGATTCTCC TGCCTCAGCC TCCCGAGTAG CTGGGACAAC AGGTGTGTGC CATTACACCT GGCTAATT' TGTATFJA GCAGAGATGC GG TTCACCA TGTTGGCCAG GCTGATCTCG AACTCCTGAC CTCAGGTGTT CTGCCCGCCT CTGCCTCCCA ATGTGCTGGG ATTACAGGCA TGAGCCACTG CACTCACCAA 35 GCACTTCTAC TGATAGCATT TACAAACCCT TMTAGAATA MAAAAA'rr CTAAGAGAAG AGTAAAT7GA GCC FTCCCAA CTAATACTAG GAGGTFATAA CCTTCATACC AAAACTGGAC AATGCTTGCA CAAAAGAAGG AAGCCAATGA GGCCACCTAG AAGGAAGACT GGGCATTGGG CCCAGTGAGT CCTGGAAACC TCATCTGTGC CAGCCACCCC GGCATGGCCT GTATGAGTGG ATGAGGGTGA C'frGTCCACA GACAATAGCC ATCTAGCTGT GATAAAGGAG TCAAGGTAGT CAGCTGCATC TCTTTCACCT GTTTGCCAAT GTT1ACACAGG TTGAAAAGCT 40 AAGGTTTATG TAAAGCAAGC ATCAAAGATG ATGAAATGAT CAACCTGACA ATGAGTACTA TGCTGCA'ITG TCCAGAAAGG AACTGTGGAA GAThITGGGC TGAA'TTFCAA AACAGAATTT CCTCACTCTC TGGATGTrTGG CTTACTTGGC CTTrGATGTT CAGAGGTGGT GCCTrGTGT TGTTGAACAA TGTTGATIT GGAGAGAAAA CAGAGTTGAA AAACCCACAA GTCATTCCCT GGGGAGTATT ACCGGAATAC AGAGGATAAT 'ITCAGCAAGC CAGCAAGGCC TCATCTCTGC TTCTAATAGA TAGGAAGAAA GGAAGAGAGG AACAATACTT TLTTAAGAAG 45 CTCAGCTrTA TCGCCTTATC TCATAGAAAG ATGCCTCCAG TCTGTCTGGC TAAAGGTAAT TGGCATGGGA AAGTCTTTAT CTGTGATTCT AACAAGTGGA ATGTCCCT TCATT1AAGAG AGCCTTGTCT GGCTTGGGGA AATGAAACAC 'ITCTCCGAT ATGAGTGGGC TGTAACCCCT GCTACTAAAT ACTCAGAAGA AATAAGGCGG TT1GTGGAGCA GTCAGGAATG AGTCACTTGC CTCCCTGGAA TA I7CAGAAA ACTGAATCAA AAGTACATTC TTCTGGGTTT TCTrAGTCTA ATAGACTAAG GGTCTCTACT TTGTTAAATT TCTGGGAAAC AGCATAGAAT 50 GGGAGAAAAA ACTGGTCACT GTAGTCATGC AAATCTGCAA AACAAACAAA AAAGTCTGGG TATTGCTGCT AACTAGCTAT GTGACCTTAA GCAAGGTATT AACTCTCTCT GAA'ITTCAGG TI1CTTCATCT GTTAAATAGC ATATCTGTAA AATGGGAATT ATITCATAT CATAATGCTG TAGCTTTAAA AAATAAAATA AAATGGATGA GATAATCAGA ATTAAAGAGC CTGGGATATA TAGTT1AATAT ATAGGAGGAT GTAAAGATCC TGTTAGAAAT GCTAA'TPTA CAGTTAACCA 'TrGGAGATG ATCCGCCAAA GCTGCTAGTG TAGAGGCAAC TGAGAATTI'G 55 CCTGTCCTITC AGAATATGAA TAAATAACTG TCAATGATGT CTCAAGCCTA GAAAAACCTA TCCATCTGGA TGGGTGGGAA AThI7CTAGGC TAGTATTGAG AAGCCCATI17 CTTGGGAAAT AGGTCCTGGA CTGAGTGAAG GAAAAGAAAC AGTAAAACCC ATGGTAAAGC AGCAAGGCTC TCTAGAGGCT CTGGAGAGGA TGAATTGAAT TCTAGAAGAT GAAGTAGGGA AGACGCIT]?A CCTTCTGTG AAATGGAYrC AAAGATTCAA AGACCTTCGG GAATCTCCAA TTGTATAAAT GGCACCATAG CTGTATGTTC CATGGAACAC TACTTCCCAG AGATGCCCAG 60 TGAAAAAAGA ATGCCACAGT CAAATAAGTI7 TGGAAACACT CCATTATGTG GCCACCTCCT TGAAGACTCT AATGCACATF AGCATGTT1AA ACAGTCTTGA GAAGTCCTGC AGAGCAGAAA TTGCTTCACA TCTGCTAAGC CGGCAGTTTC CCAATATACT TGATTATGGA TAGTTITC CTI7ACAACAC CATTCTCTGA TATGCTTCCA ATGACATGAA ATAAATATAT ATGCATGAGG TrC'ITCA'rTA GGGCATACTT ITTAATAGAA AATATTGAGA ATAATCTAAA TATAAATGCA CAGCATTTAC C=mCTGCA TAAACTATAT ACAGGCATAC CTrGGAGATA 65 CTATGGGMT GGTTCCCACA ATATCTCCAA AACCACATT1C GGTITATGA CCACTGCCAT AAAACCAGCC ACATGAAThT =TGGT~rCC CAATGTATAT CAAAGTT1ACA YTTTACTAT ACCATAGTCT ATTATATATA WO 00/62736 PCT/USOO/08020 77 CAATAGCATT ATATCTAAAA AACAACGTAA ACACCTTAAT TTAAGGCTGT GGCTGGTfG A TTffCTACC CAGACCACTA AAAC1TT'CTT CATATCAGCA ATAAGGCTGT TI1CACTTCT TACTAYTI1 TGTGATAGCA CTTrCCThr CCTTCAAGAA T=CCMI CTATTCACAA M~GTTrGAT ACAAGAGGAC TAGATTTTAG C'ITATCTCAG TITAAGGTGT TTACATTGTT AGCTAAAAAT GCTAATGATC ATCTGAGACT TCAGCAAGTC 5 ATAATCTTTTr GCTGGTGGAA GGTCYTGCCT CAGTG'ITGAT GTCTGCTGAC TGGGTGGCTTr TGGCAATTrC TTAAAGTAAG ACAACAATCA AGTTrGACAT ATCAATTGAC CCTTCCTGTC ATAAATGAVFTT ITfTITCT CTGTAGCCTG CAATGCTCTT TGATAGCAT7 TTACCCACAG TAGAAT]TC AAAATTGGAG TCAATCC'Tr CAAACTCTGG TGCTGYTI'-A TCAACTAAGT TTATGGAGTA TTAGAAATCC CTFGTTGTCA TF-CAACAAT GTTCACACCA TCTITCCCCAG GAGTATA'ITC TACCTCAAGA AACCAC TI7C TTTGCTCATC TATAAGAAGC 10 AGCTCCTCAT CCACTAAAGT TITATCCTGA GATTGCAACA ATTCAGTTAC ATCTTCAGGC TCTAC=CTA ATI7CTAGTTC TCTTGCTGTT TCTATCTCAT TTGTGCTTAC TPCTCCGCT GAAGTCTTGA ACCCCTTAAA GTCACTCATG AGGGPI'GGAA TCAACTTCTT ACAAACTCCT GTVGATGTTG ATNITPGAC CTGCTCCCAT GATTCATGGG TATTCTTAAT GGCATCTAGA ATGGTGAACG 'ITCAGAAG G=r~CAGT11 GGCTTTGCCC GGATCCATCA GACGAATCCC TATCTATGGA AGCTATAGAT TrATAAAATG TAMhC3 TITTTGTGGGGG 15 CATAGCGTCT CACCCTGTCA CCCAACCTGG AATGCAGTGG CACAGTCATA ACTCACTGAA GACTCAAACT CCTGGGCTCA AGTGATTCTT CCACCTTGGC CTCCCAAAAC ACTGGATTAC AAGCTI7GAGC CACTGTGTCT AGCCCAAAAT GTATATCATA ACTAATGAGG CTTGAAAGTC AAAGTGACTC CTTGATCCAT GGGCTACAGA ATGGACGCTG GGTTACCAGA CATGAAAACA ATACTCATCT CCTCATACAT CTCCTTCAGA GCTCCTGGGT GAGCAGGCCC ATTGTCAAAT GAGCAGTAGT ATC1TGAAAG AAATTTP TCTGAGCAGT AGATCTCCAC 20 AGTGGAC117A AAATAGTCAG TAAACTATGC TGTAAACAGA AGTGCTGTCA TCCAAGCTCT GTITCCAC TGATAGGGCA AAAGCAGAGT AGATGGCA TAA'ITCTCTA GGGCCTTAGG ATITTGGAA TGGCAAATTG AGCATTGGCT TCAAC'Tf 1TfTITfl? TTTTGAG ACAGAGTCTr GGTCTGTCAC CCAGGCTGGA GTGCAGTGGT GCAATCTCGG CCCACTGCAA GCTCTGCCTC CTAGGTTCAC ACCATTCTCC TGCCTCTGCC TCCTGAGTAG CTGGGACTAC AGGCACCCGC CACCATGCCC GGCTAATIT TTGTAT17A GTACAGACGG 25 GGTTTCGCCA TGTTAGCCAG GATGGTCTCG ATCTCCTGAC CTCGTGATCC ACCCGCCTCG GCCTCCCAAA GTGCTGGGAT TACAGGCGTG AGCCACAGCG CCCAGCCTGT CTITCAACTTA AAGTCGCCAG CTGTGTTAGC CTCTAATAAG AGAGTCTGCC TGTCCT[rCA AGCTrGAAG CCAGGCATCA TTCTCTTFCTC TAGCTATGAA AATCTTAGAT AGCATCTTCT CCCAATAGGA AGCCATIT TATGCCCTAA AAATCTGTCG TI7GGTGTAG CCACCTTCAT CATTGATCTT ACCTAGATCC GCTGGATAAC TTACCACAGT GTCTACATCA TTACTTCTGC 30 TTCACCTTGC ACTr17TATGT TATGGGGATG GCTCC'IMCC TCTAACCTCA TAAACTAACC TCCACTAGCC TCACATTCTFT CTITACAGC TTCCTCGCCT CTCTCAGAGT TCACAGAA IT GAAGAATGTF GGGCCTTGGA TrACACTm7G GTTTAAGGGA ATGCTGTGGC TGGTTTGAT7 TI7CTATCCAG AACACTAAAA CITTC TrCAT ATCAGCAATA AGACTGTTTC AC'ITCTI'AC TATITPI'GT GATAGCACTTr TrCC'ITCCT TCAAGAATT TTCCTITrCTA TTCACAATIT GACCG'TTTGA TATGAGAGGC CTAGAYTTA GCCAATCTCA GTTTACACCA 35 TGCCTTTC ACTAAGCTT1C ATCATI1AG C'TITIATI17 AAAGTAAGAT GTGTGACCCT TCC TTTCATT TGAACACTTA CATGATGATG CCTGGCTTCA AAGCTTGAAA GGACAGGCAG ACTCTCTTAT TAGGGGCTAA CACAGCTGGC GACTIAAG TTGAAGCCAA TGCTCAATTT GCCATTAGAA GCCA FTGTAG GGTTAATTAA 'TGCCTAAT TrTAATATTA TGGTGTCTCA GGGAATAAGG AGGCCTGAGT AGAGGGAGGG AGATGGGGAA ACAGCCAGTC ATCAGAGCAC ACACAACATT1 TATCAATTAA G = ATCACC TI7GAGGGCAC AGGTCATGAT 40 ACTI'CAAAAC AATTACAATA ATAAAATAAA AAATCA ITGA TCGCAGATCA CCATAACAGA TATAATGATA ATGAAAAAYF TGAAGTATTG TGAGAATTAC CAAAACGTGA CACACAGACA CAAAGTGAGC ACATGTCAITT GGAAAAGTGG TGCTGATAGA CTTACTrCAT GCAGGGTTGC CACAAATACT CAATCTGTAA AAAATTCAAT TATCTACATA GTACCATAAA AACAAGGTAT ACCTGTTTAT ATAATCAAGA CCAACAGAAC CCTAGAGAAA ATAGCTCACT CCCTAGCTCG GAGACA'TTCT AACCAACATA CAC FTACCTT TC'TITGCT GTGTACAGAA 45 TTCAAATCCC TGTCTCAGCA AAAYI7GCAAA GTATCAAATG TCATGTCCAT CTAATACTCA AAACTGCAAA TG'ITAAGTCT TGTAAGCCCA GAGACCACTG TATATACAAG TGTTGCTATA AGCATTAGTr CTrCTCCAAA GAAAATAGTC CACTTGGTAG AAACAAACAA AAAGAAAAAA AAAGAAAGAA AAAACAT1T, TACAAGAAG ATFCAGTCTC TTACCTACAT AAGCAAAAAT ATGAGATG'IT CTCTTATCAT 1TTTTCCATCT ATCTTATAAT CTTTGGTGCT GACTI'AGACA CTCATMTCC TITGTACG TGACCATGTA AAAGTTCAAG TCAAGAAAAA 50 CTTGTITGA CAFI'TG FITT GCTGAGTGAT GGGTCCCTAA AAGAAATITG GC=rGCTrT TGAAAAGYIFC AGCATGATAT TGTGTGAATT TTTCATGGCT AATGATTT AGAACAGYI'G TGATGTGM~ AGGTGTTA AGAATATGAA GCATFTCAGTG GTAAGTTG GTTGTTATAA AATGAAAGAA TATGAAGGAA AGCCTTCTTG TCTTAGAACA CACTGA'rTCA CAAATAAGCA GCTTCTCTCA AAATG'VrGTA ATTACAAAAA TTCCAAGGCA AATATAATAA ACTCCTT1GTC GGTGCTATGT CTAGAAACTT AACAGCCCCA AAGAAAGTCC TGACAAGGCA 55 AAAAATATAT ATATATATAC AAATT1GTGGA AGCAGGGTGT TGAAAGAAGA ATAAAGACTA TATAAGGACA AAGTGTTAA AAGGGAGGGT ATCCTI'GAAA GCTrGACACT TGACTCT= GACGAGGCTG AGGGAAAACA CTCAGTCA TAGATT1GCTG GTACGGATGT AAAATAGTGA CATCCCTATA GAGAGGAATIT TGGCAATATC TAGCAAAAGT GCTTATGCAT TTATTC'ITTG ACCTAGTAAT CCCGCTTCTA GGATI1AGTGG TGAAGATACA CCTCAACAAT AAAAATATAT ATACAUTAGG TTATTAGTTA TGG1TTAA FT 'TTAATAGCA AAATATTAA 60 AACAACCTAC ATGAACAAAT AGGAGACTTA CTGAATAAAC TATGGTATAT CTGTACAATA AAGTGCAATT CACTTATGTT GTTAA'ITTGT TCCAAAAATC CAGAGCCAAA GAGTAT~rGT TATGCTCTCT TI7AGTATAAG AAAGGGGAAA TAAGATATGT GTGCATCTGT TTATITTTGT GAAAATAAGT ACAGAAAGGA TAAGTAAGAA ACTAGTAAAA CTAGTTATCT CCTAGTGTTA GTAGAAATAG AATGAAAGTG AA FIAGGCTr CTTGAGTAT ATGT117ATAT ATAGTTFGA CT1TGAATT ATGTI1'ATGT 'TTACATAGTC AAAAATATAA ATTAATCAAC 65 AGAAATAACA AAAAAAGAAG AAATCACAAG CT=AAAATT TAATACAAAC AGAAATAATT GAATCTAACA GTATATCAAA GTGATAACGT AAACTCAGAA GAAAAAAACA TAATCCAACA TACCAGTGGA ACACAATATT WO 00/62736 PCT/US00/08020 78 CTAACTGTAT ACAT]7CAGTG GTTATAGTCT AAGGACAAGA AAAATTGCAA AAATATCTTG AACITTAGCT TGTAGGAMr TTA'ITGGTAG CAATACTAAT GTACTAATrC TGAAATTAAT GTrCGTGTAT TATAGAATTG AGTAAATGAA TAAATATGTI' GATGTTATTG GGAACTAAAA FrATCATTCT GGGAGTAGAG AAATATAAAT ATGGACTrGG CAAATGAAAC AAAGACCTGC AGAGAGATAA CCATATAAAC TCATrA'Ir AAAAATTATA 5 AGTGTCCTAG CTCTGTTACT GAAAAGGCCT AGATTCAATC TTATCT7GAT AGACAGGAGG GCACCCCITT CTCAGAACAT GGTITCCAAA TGCCATT1CTC CATrAAAAGG AACAAGGTCT TCTTGGAGAA AAGACTGAT7 CTAGGTCTGG A TTAGGTAAA GTACAACGL7 AGTCTGGAAT TTCTTGCTGA ATCAGAAGTA AGAAAGTGCT CAAAAACATG GGAACATGTC ACAAACACAC GTGAGGCAAC 'ITGAATCCTC ACTGGCCATA YJTAGGACAA TCGAGCATCA AAAAAAAAAA AAATG117GAG AATAATGGAT TCTAACACTT AAAACAAAAA ATAATCCATA 10 GCCCACAGAA GGGGAAGAGA GGGGGAGCTC TTATTFACAG ATGAATATCA AATAGCAAAG ACAGAAGAAA TGACAGAATT AGAGAAACAT CAYITGCAA AACACCACTG TAATAATCAA 'I1CAGGCAAG TATTATTAAT GGATGTAI17A CTATTGCGTA AAACCAGTTG GGGAACAGGA TATFCATACA GTCTGAAGGT GTCACCCTAA ACATAACTTA TTACAAGTGG AAAATGGTGC CTTTACAATG AAGAAATCTA GCAGAAACCA TCTTAATCTA GTGATCAAAC TT1AGTATCAC CAATAATGGA TCATACTGAG TCATGTGTCT CCTAATATGA TGCACCAGGA 15 AGGATGCAAC GTCATGAACG TTGTA I1C'IT TT'GTATT1CAA CAGACCACCC AGGGTAAAGG CAGC TT~CTC ACTTACTAAT CAGAATTGTT GGTITAAYP CA ITGGAT FITAAGKT CTTACTITCT TGTCAGCTCA GAAATATT TAAGATGATT TrTATC'Trr ATTCAATACT TTAGCTI'GGA GAACCATTCA GAGTITCTAA CTCATTGTAT TGCCAAAAAT AGAAAACAGC ATGG'TrTCTr TTGAAAATGT CTAAC ITIAA AGTTACTFGT GTGTGTCACT CAGATTCACA TAGC~fTT GCCTAGTAAT GTAGTATCAT GTGGCAAGGC TATAAAAATG 20 MhACAATCT TITAMflAAT ATGACTCTFG AGAG'TrATT CTAAGGAAAT AATTGAATAG TAACAAAACA CTATFAACAC AAAGCATAGC AATrGATrT GGGCAACCAA ACACTGGAAA CAACCTAAAT GTCCATJ'ACA GGAATCATTI' ATGAAGCAAA CACTAAAATA 'rITATTGTGA AGATTATGAG AACATAGAAG ACAGTTATGA GAGTAAA'IM GAAAACCTGA ACACAAAACT TACATATACT CCAA'FrGTAA C'11ATAAAAA ATACGTGCAT ATAAGGATAA AACAGTACAA ACAAAAAAAT AGT7GCGTTA GATTGGTAGA A'ITATGGCTC CYITTGCTGT 25 CTTrAA'TTr TCC=TACA YFFGATACA TTATITI'AAT 'ITTAArI=A AAA'ITCAAAA GAAITTGCCA CTCATCT-ffG CCACTTCAAG GAAAAAAGAA ATGTGTTCGA TTATTCTGTT CTTrAGTATAG rTrrGGCAAT TTCCTCACGT GTAAAAAGAG AATACTATTA ATAA'IMCAG TATCTATAAG ACAATATAAA ATTAAAGAAT CTAGCCCAGT AACTGGTACA TGGAACGTAA TTAATAAATC ATTATGGACT TrrI=CTCA CACCCAAGTA GGGAGGAATC AGTGGTCCCC TAGAGGCCCA GTGTAGAGGT GGCAGCACCA ATCCCTAGGG GAGAAGATCT 30 TGGTGATGAT AATrCCTGAG CAGACAGTTA GCTGAGAATT CAAGAGCAGA AAAGTAAGAA AGAAACAACT TCTTGCTAAC ACCITCCAC CCACGTrTCC CTGTrCTGTT GTACTCTGCT TACCCTTTCA TGGATGGAGG CAGAGGAAAG AGAACCAAGT ITGCTCTI'AG TCA'TTCACTA TGTTGTrTAA TCTGCCTTCC ATCTI'TC'TA TCAGTTCAAA TTAGAATGTA GACCTGAATT TAAATCCCCG I17CTGTCAGT TATAATGTGA CCCTAGACAA AACACATTCT CTGAACCTCA GAGAACATTC 117CA'TTGTA GAATGGGAAG ATTAATCTAT ATTCCAC'rrG 35 GATGGCAAGT CTTTTATAAA CTI'TATAACC TAAACATGTG TGAG31TGCTA GTATCATh4T GTTGGTAAAG TTATPrCTGAG ATATGATAAC AGAACTG TT TGTCTAACTC CACTAGCATG GTTCAGGTrT AGAGAGTGTG GAA'ITAAAAG GC3TIATCCT CAAATATGAC TTAAATCCGA ThITCTCAT CCAC'ITTCCT CCACAAACAA ATCCTCAGGA AATGACAAAC TI'ACATGGT TAAACATCAG =ITGTTTAG TC'TTTGACAT CCACATGG11 AAATCATACA T=GAAAACT GCTTATA'Tr GTGTrGTCTA TGTCTAAMTT GAAAAGACTT APFGAGGAAT 40 AGAAGACTAC ACATTMCA GCAAACACTG CACGTTTGC AGAATTTCCC CAGGCACCAG TCTCCAGGAA = TTGGCT ACTAACAATA CTAAGATATG GATGAATGAG GAAATCAAAA TGGAGATC'rr GCAAG'ITI7G TGAGAATGGG TGAATGGTCC AAATGAAGAG ATAAGTTGTG AAATATTAGT ACAAGTAAAA ATTA3TTACA ATGAAAGACA TITTGTCAAT AGCTATGAGA A'TTrACCAT TGACCCAGAA ATJ7CCATI1?C '1TTCTT1CAGA AATACCCACG TAGGTATACA TATAAAAAGT TATTCATT1AC AGTATCG'I= TTCATAGGAA AAAGFTrAA 45 AAATCAGAAG CTATCTAAAC TATGGTATAT CTAGGTCATA GAAATCAAAT GACTAAAAAT G-FAATATAA GCATATGYPT '11AAATTAAC TTGGCYI'GGG TCTI'CAGCAA AATTGGCTTC TTAACATrGC ACTCCAGAGT TAGACTTACC CACTCAGTCA CTTATCATGC AGGAGCAGAC TCCTAATACC ACATATCATA GAGCAGAGTA GGACACAGGT TCTCTGCAGG CAGGCAAATC CCAAAGAGAA GGGAGGAAAG GGCTGAGACA CTGCATGGTC AATTTCTTCT GAACTCTGCA ATGTACGGAG GTGGACAGTG TCCACAAAGA TTGCTCCCCT GGACCCACCA 50 TCATAATAAC ACAACGGCTT TGTITGMP TTGTITMGT TTrGACAC GGAG'IIGC TCTTGTTGTC CAGGCTGGAG TGCAATGGTG TGATCTCGAC TCACCACAAC CTCCACTTCC TGGGTTCAAG TGATrTCTCCT GCCTCAGCCT CCTGAGTGGA TGGGATJACA GGCATGCACC ACCATGCCCA GCTAAT=TG TATTTTTAGT AGAGACGAGG TTTCTCCACG TTGGCCAGGC TGGTCTCAAA CTCTTAACCT CAGGTGATCC ACCCGTCTTG GCCTCCCAAA GTGCTGCGAT TACAGGTGTG AGCCACCGCG CCCAGCCCAC AATGGCCTI1? TG'TrTACATC 55 TCTAGTGCAG CACTCATTTC ATGTTCYITC AAGAAGAATA CATATI1CAT C'T'IAT TATACAGCAA TT1AGCACAGT GCCTGGCATA AGGAAAATGA TCATTAAAAG CTGGGTGAAA AACCTAATAA AGCTACTGAG GATAGGAACT GCAGACCAGC ATGGAAAGAA AACTATGAGC CAGATATTGA CATCATCCTG AAAGGCAGAA GA'TTIAGTAT AGGCAAGAAG TATGC=flG GAATATAGAA AATCTGGA'T ATGATAAGAA AAGAATCATA TnrGTCTrAT CTTACCTACT CAC'ITCTCAG TTCCACATGT 'ITCTGAGGCT G'TrGTCCTT ACICTITT= 60 CTGTTTTATC CACTCTTTCT GTTCTTTAGA TTGGATCATTr CCTATTGAGC TGACATCAAG TTAACTGACC T'TrATTTTG TCCAAACTGC TGTTAAATGC ATCCAGTGAA ThTTTAACTT TATATAGTAT ATCFFL17AGT CCTAGAATTT CCACATGAGT 'TI=AAGTT TCCAYITCTC TGCTGAGATC TCCTATTTGT TCATTCATTA TGACCATATT TYPTCTCTACA TTATTGAGCA TAATI'ATAAC AGCTCTFCTA AAATTCYI'GT CTGCACATITC TAACACCTGA ATTATTCTGG GGTCAGTCTC TGTTACATTG CC ITATTACA AAAACAGTAT AAGTCACATT 65 GCCTTGMrC TTAATATGCA AAATGATH TGATTGCAGA CTAGACATI7 TGAATTAAAC ATTrATAGAGA TTCTGGATTC TCGAGAGAGT ATrGACTTGT TITTFCCATC AGGCAGGTAA CTTGACTGGA CTCAAACTCC WO 00/62736 PCT/USOO/08020 79 AAACTCTAGG TCCTCTGTAA TGGGCAACTG CAGTAATCTT TGTTTAGTTC TTTAAGACTT ATTGGCCAGG CACGGGGGCT CATGCCTGCA ATCCCAGCAC TGTGGGAGGC CAAGGTGGGA GGATCACCTG AGGTCAGGAG TTCGAGACCA GCCTGGCCCA CATGGTGAAA CCCTGCCTCT ACTAAAAATA CAAAAATTAG CCGGGTGTGG TGGTGGGCGC CTGTAGTCCC AGCTACTCAG AAGGCTAAGG CAGAAGAATC ACTTGAACCT GGAAGGCAGA 5 GGTTGCAGTG AGCCGAGATT GTGCCACTAT ACTCCAGCCT GGGTGACAAA AGCGAGACTC CCTCTCAAAA AAAAATTTAT TGGCACTGCT TGGCATCTGC TATGAATACA TGAAGTTCAT GGGTCAGCTA TAGATCTGGG CACGTTATAC ACAGAATTTG GGTCTCCCTT TCTCTGGATT TCTCCTTTTC TGGATTTCTT TTCTCATTTT CCAGCAGCTG TGGTTGCCCT AAACTCGGTC CTCTGTTTCT TTACGGCAGT AAGATTTGGG AACTTTTAGG TTTTACCTGC CTCTCAGACA AAATAAAAAA TAATTTTCAT CTTGATGCTA CTCCTTTCTT CCAGATGTAG 10 ACACCTCTCT AATTTCCAGT TGCTTTTTAT TGCTCTCCAG AGTCTAAAGA TTATCATTGT TTTCTGTGGG AGAGTTGGTC TGATAAAAAC TACTCCCCCA AAACTGGAAG CTGGAAGCTT GTAATTATGA ATAGACTTTG AGTAGTATTC TTCTTTGGAA AAGGATTTTA ACTACTCCCT ATGTACTTCT TTATTTCCTG TTTTTCTCAT CCGTAATCTT TTTATTTTCA TACTTCCTAA GTCAGACAAT TTTCCTACTT GAAGATTCAG TGACTGCTAT CAAATGACCC CCATATTACT AAATACAATA TCCCCAACTG CATTTATAAA AAGAAAATTT ACTGTTTATT 15 AGTAAACAAT GTTGTAGAAT AGTAAAATAT TGCTGGGCTT TGGAGCCAGA TAATCAAGGT TAGAATCCCA GATTCTAACT TACTAGCTGG TGTATTAGTC CTTTCTCATG CTGCTAATAA AGACATACCC CAGACTGGGA GACTGGGTAA TTTATGAAGA AAAGAGGTTT AATTGACTCA CAGTTCAGCA TGGCTGGGGA GGCCTTAGGA AACTTACAGT CATGGTGGCA GCAAGGAGAA GTTCCAAGCA AAGAGGGAAA AGCCCCTTAT AAAACCATCT GATCTTATGA GAACTCACTC ACTATCACGA GAACAGCATG AGGGTAACTG CCCTCACGTT TAATTACCTT 20 CCACCAGTTC CCCCCCATGA CACATGGGGA TTATGAAAGC TATAATTCAA GATGAGATTT GGGTGGAGAA ATAGCCAAAC CATATAATTC CACCCCTGGC CCCTCTCAAA TCTCATGTCC TCACATTTCA AAACTCAATC ATGCCCTCCC AACTGTCCCC CAAGGTCTTA ACTCATTCCA GCATTAAGTC AAAAATCCAA GTTCAAAGTC TCATCTGAGA CAAGGCAAGT CCCTTCTGCC TATGAGCCTA TAAAATCAAA AGCATGTTAG TTACTTCCTA GATACAGTGG GGGTACAGGC GTTGGGTAAA TACACTGATT CCAAATGGGA GAAATTGCCA AAACAAAAGA 25 GTTACAGACC CCATGCAAGT CCAAAACCCA ATAGGGCAGT CATTAACATT AAAGTTCCAA AATGATCTCC TTTGACTTCA TGTCTCACAT CCAGGTCACA CTGATGCAAG AGGTGGGCTT CCAATGGCCT TGGGCAGCTC TGCCCCTGTG GCTTTGCAGG GTATAGCCTG CTTCCTGTTT GCTTTCAC AGGCTGACAT TGAGTGTCTG TGGCTTTTCC ATGAGTATGG TGCAAGCTGT TGGTGGATTT ACCATTCTGG GGTCTGGGCC AGGTGCAGTG GCTCATGCCT GTAATCCCAG CACTTTGGGA GGCTGAGGTG GGGGATCACA AGGTCAGGAG ATCGAGACCA 30 TCCTGGCTAA CACGGTAAAA CCCAGTCTCT GCTTAAAAAA TACAAAAAAT TAGCCAGGCG TGGTGGTGGG TGCCTGTAGT CCCAGATACT TGGGAGGCTG AGGCAGGAGA ATGGCGTGAA CCCAGGAGGT GGAGCTTGCA GCGAGCTGAG ATTGTGCCAC TGCACTCCAG CCTGGGCGAC AGAGCAAGAC TCCATCAAAA AAAAAAACAA AAAAACCATT CTGGGGTCTG GAGAATGGTA GCCCTTACAG CACCACCAGG CAGTGCCCCA GTGGGGACTC TGTGTGGGGG CTCTGACCCC ACATTTCCCT TCTGCACGGC CCTAGTAGAG GTTCTCCATG AGGGTTCTAC 35 CCCTGCAGCA AACTTCTGCC TGGACATCCA GGCATTTCCA TACATCCTCG GAAATCTAAG CCGCGGAGGT TCCCAAACTT CAATTCTTGA CTCCTGTGCA CCCACAGGCT CAATACCACA TGTAAGCCAC CAATGCTTGG TCAGGGCTTG AACCCTCTGA AGCAATGGCC TGAGCTGTAC GTTGACACCT TTTAGCCTAG ACATCTAGGA CACAGGGCAC CATGACCCGA AGCTTCATAA AGTGGGAGGG CCTTGGGACT AGCTGAGGAA ACCATTTTTC CATCCTAGGC CTCCAGGCCT GTGATGGGAA GGGCAGCCAT GAAGGTGCCT GACATGCCCT GGAGACGTTT 40 TCCCCATTGT CTTGGTAACT AACATTCAGC TCCGTGTGCA GCACCAACTT ACTTATGCAA ATTTCTGTCA CTGGTTTGAA TTTCTCCCCA GAAAACAGGA TTTTTCTTTT CTATTGCATC ATCATGCTGC AAATTTTCAA ACTTTTATGC TATGCTTCCT GTTGAAGACT TTGCGGCTTA GAAATrTCTT CCCCCAGATA CCCAAAATTA TCTCTCTCAA GTTCAAAGTT CCACAGATAT CTAGGGGACA AAATGTTGCC AGTCTCTTTG CATAGCAAGA GTGACCTTTA CTCCAGTTCC CAACAAGTTT CTCATCTCCA TATGAGACCA TCTCAGCTTG GACTTAGTTG 45 TCCATGTTAC TATCAACATT TTGGTCAAAG CCATTCAACA AGTCTCTATG AAGTTTCAAA CTTCCCCATG TTTTCCTGTC TTCTAATAGC CCTCCAAATT TTTCCAACCT CTGTCTGTTA CCCAGTTCTA AAGTCACTTC TACATTTTTG GGTATCTTTA CAGCAGTGGC ACTCCCCATG GTACTAATTT ACTGTATTAG TCTGTTCTCA TGCTGCTAAT AAAGACTTAC TCGAGACTGG GTAATTTATA AAGAACAGAG GTTCAACTGG CTCACAGTTC AGCATGGCTG GGAGGCCTCA GGAAACTTAC AAACATGGTG GCAGCAAAGA GAAGTTCCAA GCAAAGAGGG 50 AAAAGCCCCT TATAAAACCA TCAGATCTTG TGAGAATTCA CTATCATGAA AATAGCATGA GGGTAACTGC CCCCATGATT AATTTACCTC CCACAGGGTC CCTCCCATGA CAGGTGGGGA TTATGGGAAC TACAATTCAA GATGAGATIT GGGTGGGGAC ACAGCCATAC CATGCCAGCT AGAGAGCCTT AAGAAAGTCA CCTAATCTCC ACAAATAAAA GGTTTCCTAT TTGTTCAACA AAAATAATGA CACCCCTTTT ATGGGATTTC TGTGAGGACA AATGATAACT AACATAGCCT TGCATAGTGT CTGGCACAAA ATAGCTACTC AAAAAATAAT AGAAACAACA 55 TTTAAAAAAT GTAGACTTTA TTTTTTAGAG TTTTATGTAC AAAGCAAAAT TGAGCAGAAT GTACAGAGAG TTTCCGTATA GCACTCCCTA CCCCCAAGCA CAGATAGCCT CCCCCAGTAT CAGCATCCCG CACCAGAGTG GTACATTTAT TATAACTGAT GAATCTATAT TGACGTGTCA TTTTCATCCA AAATCCATAG TTTATATTAG GGATGCCTCT TGGTGTTGTA CCTTCTATGG GTTTTGACAA ATGTATAATG ACATGTATTC ACCATTACAG TATCATAAAG AATAGTTTCA CTGTCCTAAA AATCTTTGAT CTTCTTCCTA TTCATCACTC CCTCCCCATT 60 AATCCCTGAC AACTACTGCT AATTTTCCTG TCTCCATTGT TTTGTC'TT CCTGAATGTC ATATAGTTTA AATATACAGT ATGTAGGATT TTCAAACTGG TTTATTTCAC TTAGTAATAT GCATTTGATG TTCTTCCATA TCTTTTCAAA GCTTCATAGT TCAATATTTA TAGAATTGAA TAATATTCCA TTGTCTGGAT GTACTACAGT TTATGTATTC ATTCACCTAT CAAAGAACAC CTTGGTTGCT TCCAAGTTTC AACAATCATG AGTAAAGCTG CTATAAACAT CTATGTACAT GTTTTTTTGT GAATTGAACA TTTTCAGCTT TTTTAGCTCC ATTCCTAGGA 65 GTGCAATTGC TGGATTGTAT GATAAGGGTA TGTTTAGTGT TGTAAGAAAC TGCCACGCTC TTCCTAACTG GATGTACTGT TTTGCATTCT CACCAGCAAT GAAAGAGTTC CTGTTGCTCC ACATACTCAC CAGCATTTGG WO 00/62736 PCT/USOO/08020 80 TGTCGTCAAT GTTTGAGCA ATAGCA'TIT GATCTAACTT TCCTAGGTA TTCTJTFGA AGGAAATAAT ATGACAGATA ATAGAGAAAG GATATAGGAG GACAGTI'CTG TCC ITTATTT ATAGTCCATC ArTAATGAA GGACTCTGTC CACAC317GGT ATFITTAACT CTGATCCTCC TCTCCCATGA ACTCTGACAA TCTCCTAAAT CCCTGTTGCT GGCACACATG GTTGTGTATC AGGCCCCCTG TGGTCTGTCT GAAGCATGGC TT1TTTTLT 5 T7ITTI 'FTrGAG ACGGAGTCTC GCTCTGTCGC CCAGGCTGGA GTGCAGTGGC GCGATCTCGG CTCACTGCAA GCTCCGCCTC CCGGGTTCAC GCCATTCTCC TGCCTCAGCC TCCCGAGTAG CTGGGACTAC AGGCGCCCGC CACCACGCCT GGCTAATITT I1GTAThIT AGTAGAGGCG GGGTTTCACT GTGTTAGCCA GGATGGTCTC GATCTCCTGA CC'ITGTGATC CGCCCGCCTC TGCCTCCCAA AGTGCTGGGA TTACAGGCGT GAGCCACCGC GCCCGGCCTT 'TfTTI17 TTrmlTI= TI"TGAGATGG AGTCTGTCAC TCTGTCACCC 10 AGGCTGGTGC AGTGATGCAA TCTT1GGCTCA CTACAACCTC CATCTTrrCAG GTTCAAGTGA TTCTGCCACC TCAGCCTCCC AAGTACCTGG GATTACAGGT GCCCGCCACC ACACCCAGCT ATITTTTGT A'ITITAGTA GAGACGTAGT TTCACCATGT TGGCCAGGCT GGTCTCATTC CTGACCTGA GTGATCCACC TGCCTTGGCC TCCCAAAGTG CTGGGATTAC AGGCATGGGT CATCACATGT GGCCTGAAGC ATGACTGTTG C TrAATCAT ATGAAATACT GCTCTGTATT GTI7ATCTAT TGAAATGCCA CACCTCCTGA GCTAAATTGC AAGCT1TAT 15 GGAGCACAAA CCATATTTAT ATATATTAGC ATGATACCAT GACACATATC AAAAGCTGTT ATATATTGTT ACGTGAATI'G A FTCTTTCTC AGTI'AAGAGG ACCTCTGTAG TAGCACTITC ATACCGTTAA 'FPITTCAT TGTGCCCAGC CCCTACTCTG TGAAAAATGA AATGAATCCT G'I1ATCATTT CCCTCCCAGG CCTITCTCC TTGTGGACAA TGTGTGGCTC AAGAGAAAAT TCAGTCAGTA AAT17GTTCA GTGCACAAAC TCTITATCAC CTCTCACTGT TCTCAAGTGA GATAGAACAG AACATCCATC CAGTGTCT-FA CAAATTGTCT GGTATATAGT 20 AGGCACTCAA TAAATGTTTT TTGAATAAAT GCATACATGA ATCCTATTCC TATATATAGT ATGGTAGACA GATCATTGAT ACCCAAAGAT GCCCAAATGC TGATCCCCAG AAC'ITGTGAA TATGYFACAT TTCATGTCAA AAGGGACTTT GCTAATGTGA TTAAGGATTC AGACCCTTGG ATTGTAAGAT TATCCCGGAT TAACCAGGGC CAATCTAATC ACATGAGACC TITAAAAAAGC AGAAAACATT TCCCAGCTGG GTJ7AGAGAGA GATGAGACAG AGTAAAAAGG AAAGAGATT1C AGGGCATGAA AATGACTCTA CCCACTGTTG CTGGCTTTGA AGATAGAGGA 25 ACTAGGCCAC AAAACAAGGA GTATGAGTGG CCYrAAGAAA TAGGAAAAAG CCCTCATCTG ACAGCCAGCT AGAAAGCAGT CCTCTGACCA CAAGAAATTG GATTCTGCCA ACCACTCAAA TGAGCAAGGA AATGGATTCT CCCCTAGAAC CTCCAGAAAG GAACACAGCT CTGTAATGCC FTGA L1TTAG CCAGGTGAGA CCTGTrTCAG ACTrrGACC TATGGAAATA TAAGATAATA AAGTTTFATT GTATGCTGCT AAATTTGCGG TAGTETATTA CTGAAGCAAT GGAAAGCCAA TACAGACAGA ATATACAGAG AGAAAGAGAA TGAGTTCTTr CCTGATAATT 30 TGTAAATATI' TGGGTC'I1CA CTGGACAAGC TTCACAGAGG ATTCACTGGT TCCCTAGCAA ACCAGCATGT CCAGTCCTGC AGCCTCCCTT TC'ITAGGCCC AGCATATGTC AGCTGTGTGC ATAGAAAAAT CAAAGCAGGA CCCTGAGTAG TTGGAAAGAA AAGATGGTTG GAAATGGGTT GCACTTCAAG TGAGGAAACA AGAGGTAGGA GACCGGCATC TC'TTTCTCAT ATGTCCCAGG CTGACTCTTG TGAG7FGTFT TCCC'I1GGAG GCTATCGATG ACAGTCACAG TAACCTGATG GAACCTGGAT CATGATGAAA GAAGTAAGTG TCAATGGCTC CGACTI7CCAA 35 GGACTCTGAT GTCCCACAGC ACTAGCTAAA CAAAGCCAGT TGGAAATGAG C'ITAAATGGG GAA'ITTCCTG AATATATrCC CTATTGTTAG GAAGCCAGGT TGGCTrCCTT GCCTACAATT ATGCCAAGCA GTCACACTAT AGAGTCCCTA GGGACATGAT ATTAAGTGAT TCTIJAACA CAAACAAC117 AATAATCATr TATACTAATA GCAAAACGGC CAACGGCTGA TATTCCACTT GAAGTAGAAT TGGCTATCCA ACTGGAAGAG AAGACAGGAA GACGTGATCT CCAGGGAGCC ACTAAAAGGA TTGGCACCTG CCTCTGGATT CCCCTITTTCC TL1ATATI7ACC 40 TCTCAGCACT GGCAGGCCYI' TA'TrTCAGGA TACAGTI1TCA CAAGTATTAT GTCACGTCTC TGAGAATTAT GYFGGTAGAT ATITGCTCCT CTGGCCAGAA AGACCTAGYI? TGGAGTCTGG AGTCATGAAG GTGACATACA TGTAGCTAGT GACATAAGTG TAGCTAGTAA AAATAGTGAG TAATGGCCCT GAAATTCTAT TGAATGCCCA AAGTGCTGAC CAGGAACAAG CATGCTCTAG C'ITATCTCAC AAGGAAC'ITG ACAA II1CT TCAAAAATCC TAGTAGCTAA GA'ITTCTrAG TAACAAAGCC ACTAAGGCAC AAT7ATGAYF AACTTGACCC TTAGGTGACT 45 T=TAAGGACT ATTCTATAAA ATATTACAAC TAATAGTGGA TCCAAGCCAG CACACTCTGC TATATAAGAT TAATI1GACAG TGTCCACACT GGTAAAATAA GTTG=TCAT AAATACATTA GAATTCATT GCACTTTCTA CACAGCCCCA AGTCCAGAAC 'TrCCCCAGA ATAGGTCTAT GVM~GCAAT CTGCTACTCC ATACAGAGAT T'TGAGTTCAC TTGGCAA=L AGTGCTGCTI' ATATGTGACC AGrrAGTCTG TJTfACTTAT CTATGCCTA AACATTACTA TACTTACTAA CTCCAAGATG CCTGGTCTCA ACI17GACAAA AATACCCCAA GTTGGGAAAT 50 CCTTATGTGA ATATGTAGAT AGTCACAA'rr GCTGGTTGAT GATGATCTGT CT1TCCTGT AYPTGAGAAA ATGGAGATAA AATGGACCAA TCCAAATAAT GGATTAAACA TGGGAATAGG TGAGAGAGAG AGAGGAATAC ATGGTGGCTC TCAGTGTCTG GCTTAGGCAG TAAACAC'IT CGTTAATAAA GACGGAAAAT AAAAAAGGAA TAATrFGGTGT CTAGGGGAAA ATAATGAGCT CAAGTITAA CACTCTGAGT TCCCGGATGT GAGACATCCA GGCGCATTTA TCCAAGAGGC AG'I7GGAAGC AACGTTCCGG AGCTTAGGAG AGAGGCATGA CCAAAAGCTG 55 GTGGGACTGT GAAAAGGTAT GGCCATTCTG GAAAACTGTr TGGCAGT1TTC TrAGAAAATrr AAACATGTAC TAACAACCCA GCAATTGTAC TCTTGAGCAT TTGTCCCAGA TAAATGAAAA AAAAAAAAAG CATTTITIT ACACAAAAAC ATATACATGA AAGTrCATAG AAGTG ITATr CATAAAAAAC TGGAAAAAAC TGAGATGTCT TTA F7GAGTG AATGCTTAGG CAAACGGTGG TCTATCCATA CAATGGAATT ATGCTTAGCA ATAAAGAGAA AAGAACTAYI' GATACATGCA ATAACACAGA TGAATCTCAA AGGAATI'AAT GCTGAGTGGG AAAAAAAGCA 60 CATCTCAAAA TGGTATATAC TGTACTATTT1 TAT1T7ACTTA ACATI=AAA AATAGCAAAA TCATAGAGAT GGAGAACAGA TTAATGGGTA CTGTGT1TG GGATGGGGAG TGAGAAAAGG GTAAGGTGTA AATATAAAGG GGTAGCACAA AAGAGCCTTG TGG317GAAGG ATTCTATGTC TTGG'I7GTAG TCGTGATrGC AGGAATCTAC ATGTGATAAA A'ITGTATGGG TCTACATACG CATACACACA AGAGCATATA AAACTGGTGA CATGTGAAGA AGCTCCGCAC ATTGTGCCAA CATCAGTATC CTAG'IMCAA TATCAGACTA CAG'rrATACA AAACA FTGTC 65 ATTGAGGGAA ACTGGGTAAA GGGAACACAG GACAITTGGC ATATATTT GCAATTTCCT GTGAATCCGT AAT7A ITAA AAATAACAGA TATACTACAT ATCAAAAATT TAATGTCATA AAGTI'GATGA GTACCTAG WO 00/62736 PCT/USOO/08020 81 TGGATAGC'r TG'ITAATATC TGCTATAAGA CTACTGAAAA TGACAGT~rAT GCAAGTATAA GCTCAGAGAA C'ITTCCTCCC CCTTCGTAAA TGAAATGAGC AAAAGAAATG AAACAGGAAA GGCAAGCAGT ACTGAAAACA GGGAAGGGCT CTTCCCCATA TAACTATATC TGCGACTrCA ACAGCTATTC ATCCAGAAAC ACAGCCTCTT GCGCTAAGAG GAAACTTrGG ATAACAATAT GT'TrCACTC TCCAAGAGAG AAAATGGATA GATTAATITTT 5 TAAGAAAAAA AAAAAAACCT CACCAATTTC ATGCTGTGGC TrGCACC'ITT AATCCCAGCT ACCTACAAGG CTGAGGTGAG AGGCTTACTT GAGCCCAGGA GTTCAAGGCT GCAATGAGCT ATGATTGATT GTGCTATCGC ACTCCAACCT GGAGTACTAA GCTAAGAGCT AAGAACACAG CTGAGAGCGG AGAAGAAACA AACAAATCTG ACCAATAACC CCCACTCCCC TCATITACT GGAGTGAGCT GAGACTGCTG GCAAACATGG CCITrGACCT AGCCTGAACT GTAGCAAAAG TCATCAGATA TTTCCACC AATCAACAGA CAGAAGTGGG GAGAAAACAA 10 TCGTAGTTCA TAACTACAAC AAGCAGATAA ACGAAGGCCA TGGTGAGGGA TGGAAGACAT TGTGATATAT CAAAGGCAGG CTCA TTAAA ACTCAACCCA AATTCCAAAC AAAATATATA ATTGAATATG TATTAATGCC AAAGGAGCTT GAGTGAGCTT TAGCACAAAC CCCGCCCTCC AGCCCCCACC CAAAAAAATC ACTCTGTTCT CTCCCCATrTC TTTGATAGGC ATACTTGCTG TTT-FCTCACA GCCAAGGTAC AGAGGGGACT TAGAGGAACT AGAACTCTAA TACACTGCTA GCAGGAATGT AAAATGAAGC ATCTACTTCA GAAAACCA'rT TTATCAGT~ 15 CTAGAAAGTT1 AAACATAGAC CCACCATGCA GCCCAGCCAC TCTACTCCTA AGTATTTACA CAAGAGAAAT GAAAACGTGT CCCCACACAG TTGTATTTAA AGGTGATGGT TAGCC I1GTG TGTCAACTTG GCTAGGCTAT AATACCCAGT TACTGAATCA AATAGTAATC TAGGTGCATC TGTGAAGGTA T=~GTAGAT GTGGTTAACA GCTACAATCT GTGAC'FrCA AGTAAAGGAG A'I1GCTC11G ATAGTATGGG TGGGCTrCAT CCAATCAA11 GAAGGCCY'TA AGAGCAAAAA GTAAGGTTTC CCGGAGAGAA AGAAA317CTG CCTCAAGACT GCAGCCTCAA 20 CTCCTGCCTG AGTTCCAGT CAGCCAGCCA GCCTAAAGAT TTGCTAGGCA TTATAATCAC ATCAGCTAAT TTFCTTAAAAT AAACCTC'ITT ATATATATrO ATACAATGAA TGGT7ATAGC AGCCTTATT GTAATAGCCA CAAACTGGAA ACAACCTAAA TGTCCTTCAA TAAGTGAATA CATAAACAAA TYFGTGGTATA TCCACAATT TTACGCAGCA GTAAAAAGGA ATAAATGGTT GAATAAGGAA TAAACACATA ACAAGGATGA ACCTI7AAAAC CGTAAGGCTG AATGGAAAAA GTCAGACAAA ACTAATACAT ACTGAATAAT TCCATTTATA YI7GAAGTTCT 25 AGAAAATGAG GACTAACCTA TAGTAACAAA AAGCAGAAAA A FTIGCCCA CTGGTGATGG AGGGGGCGCA GGTATTGTAG AGTATCTGAG AAAGGACAAC TGGATAAAAG GGGGCACAAG AAAACT=G AGGGTGATTG ATATGTTCAT TATC'TGTGG CATGGTTTCA TAGGTGCATA CATATGTCAA AACATCAAGT TATACAC'TTr TAAAATGT-rC AGTTTACTGT ATATCTAYIA TACTTCAGTA GAGAGGAAGG AAGAAAGTGG GCAGGGTGGG GGAGAGGAAA GGAAACGAGG GAGGAAAGGC CCTAATAGGA AGGATITGG AG'ITTAGATI' TT1AAAATGAT 30 AAAGGATGTT TGACACTCTA GGCATATGAC GAATATAGGA TTATGAGTCC ACAAAAACCA CCAGGAAGTC ATGTATGT[rT ATACTTAA GTGAAGGATC AGTGGATTAT CAACTCCCTA ATGCITT7GCC TCTCTATGAC TGGCTGCTGT CCTrCTCATC CCAATACTCC TTCCAAAGCC CCTTGCTTAA ATGTAAGCCT TC TTCCTCC TITCAACACA TCCTGCATTC CGTGACAAAA TAAGThCC TI'AAACAGAA TGTACAGCAT ATJ7ATTTGTA CAATT1AAAAA TITPGGCCA GGTGTGATGA CTCATGCCTG TAATCCCAGC AA'TrGGGAG GCCGAGATGT 35 GTGGATITACC TGAGGTCAGG AGTTCGAGAC CAGCCTGGCC AACATGGTGA AACCCTGTCT CTACTAAAAA TACAAAAAT7 AGCTGAGTGT AGTGTGGCAG GTACCTGTAA TCCCAGCTAC TCAGGAAGCT GAGGCAGGAG AATCGC L1GA ACCTGGGAGG TGGAGGTTGC TGTGAGCAGA GATCAGACTA TTGCALTCTA GGCTAGGAGA CAGAGTGAGA CTCGGTCCCC AAAAAAAAAC ACATTTT MT rAATGTrC CTCCTFGCCT GTAGGAAAAA GGCTCTGACT CCTTAGCCTG GGCATCAGAG CTCTATCTAA ATGGACTrA ACCTGAT=f GTGGCACTAA 40 TTCCATTGCA GTACTTGTCC GCTCACTGGC CTGTGCCTCT CTGCCACTAT TITGGAATA ATGTCCTCTC TCCATCTTGT TTACTCAACT ATATCCAACC TCTAAGGCTG TGCTCCTACA AAGCCTCCCC TGGCTACYI'C AGCCCACAGA GATATrAAC TGCTCTGCAG TT1CAGGACAT TCT-TCTGACT C1TTAAATCA CAT1TACTTA TATATGATCT TGTGATA'ITT TTTGTTGACG TGTTTACT117 AA'ITCTTC CATAACCTAT TCATTCAACA AACTCAACAA TTAT1TA'I1A AATGCCAAGT TAGAAAAATA TrATTGATrT TATATAGATT ATAGATATGT 45 TTGAAAT=T ATITGGCAAT CTGCAAGTAG AAAAATAATr ATAATGTGGT ATATCTGTGA TAGAAGTAL1 AGTGCAGAGA CCATGGGGAA CATAATCCAG CCTGGAAGTT CAGGAGAGAT ACGTGGAAGA AAGGACGTCA GAGCC'TTI CCTACAGGCA TGGAAGAAAC ATTAAAAAAA ATTTTI TTGAGATGGA GTCTCACTCT GTCTCCCAGC CTAGACTGTG GTGGTGCGAT CTCTGCTCAC TGCAACCTCT GTCTCCCGGG TTCAAGTGAT TCTCCTGCCT CAGCTTCCCA AGTAGCTGGG A'ITACAGGTA CCTGCCACAC ATGGATGATA AATATGATCA 50 TATITTCTTG 'ITCYTT-CCT CCTCAGTGT CTTCCCTGAA GAAAGGAATG CCTITTATAG ATGACAAACT CCCATTrCTCA AGAACAAGGA 'T1TGACCA ATrAAT=A ATCAGATGTC TGGCITT7GAC CTAGAAACAC AGTCACGAAA CTTGGTGATT AGAGACCAAT TCCCAAACAT GAGCATTTCT TAGGAAACAC AGTAAAGATC TGAGAGACCC AAGAGCAGAA GGGCGAGAAA CCAAAAGCCA TCAGT'ITGCA TAGGAAACAC CTrGTTTAGC CTAATCTT TATL=ATT ACTCTATTAG TCACTACAAC TA1TFCTGA TTGCTATGGT GATAGATGGT 55 TTAAAACAAG CCTI7CATTAA GAATTGTCAC ACCATGGTCT CAGTCAAAAA CACCAACATT TPTA'VrGGTA TTGACAATTA TGGGAATATC CAATTCCAAG AAGACAAGGA GACCTCTGAA CT=CTAAAT GAAGACTCCA ATC ITCCTGA TCTGATGGGA AGCAGCTTGG CAAGATTACC AACCACCACC ACAGAGAGTG GACTCTAAGC TAAGACTTAA AAGATAAGTA GAAA'FrATCC AGGTAAAGAT GTGTACAGAG AAGGAAGTAC ATCCAGGGGA AAAGAACAAT ACGTGCAAAA GTACGGAAAT GGTAAAAAGT AATACTACAT AGTCAAAGCC AAGCAGAGTT 60 CAGAAGGGAT CTGGTGGTGA AAAATACGGC TAGAGAAAGC AGCAAGGA'IT GGC'I7CTAAA ACCTATGTAG TATCTTGGAC C I1ACCCTAA ATGTAATGAG AAGCT'FCTAA AGAATCTrC ATTTATTCAT TCATTGAACA AATAT'IrTGA GGCTTTCTGT GAAGAACATC ATT1CTAAGTA GTAAAGATAC AGCAGTGAAT AGGACACATA AAATCCTAGA TCTCACAGAA TTGACAFCC AGAGAGGGAA AGGTAGACAA TAAATACATA AACAAATCAT ITrAACAAGAT GATTTCAGAC AATGGTACGT ACTGTGAAAA AAATGAAACA AGGTAATGGA CAGCGAAAAG 65 GCACTGGAAG GAAGCCTGCT TACC1TGCA TGGYFAGAAA AGATCTCTCT AAGAAAGAGA CCACATGTGA GCTGCGACCT GAAGGATACC GAGAAGCTAG GTGTGCAAAG ATGTGGGGAC AGAACTTG GACTGAATAG WO 00/62736 PCT/US00/08020 82 CAAATACAAA TGCCCTTGGG TGCAAGC'1TT GCCTGTrCAA GGACCAAAAA GAAGGCCAGT GTGCCTGCAG CATACTAAGC ACAGAGGAAA ACACTGTFAT ATGCTGAGAT TGGAATTATA AGTAGAGCCA GATAATATAG TCTCTTATAG GTCATAATAA GGCAACCAGA TITTATTCCA AGAGGA TTA AAAATCACTG GAGGTrTGC ACTAGGGTGA GAGGTGTGAT TTGTATITT AAAAGATAAT TCTGGAGAAT TAACTATAAT GAGGTAGGAG 5 TAAACTAAGT TAGGGGCTAT T[CAGTGGCT CAGACAAGAG ATAATGGTAG CTTAGACTAG GATAGTAGTC GTAGAAATAA ATAAAAGTGG CACTCTACTT TGGGGGTAGA GTCTATAATA GG'TrGGTTr ATGGATCATA TATGAGAGTA AAAAAAAGAA AATAAATTAA TAATGGTTCC TAGGTTTGTA CCTGAGCAAC TGAATAAATG GGTGCTGTGA ATTGAGATAA AGGAGATTGA GAATCACAGG CTITGTITG CAAATTAATT TTGAGAGGCT TAYFAGACAT CCCAGTGGAG ATI17CAGGTG AGTGGAGCCC A17GAAAGGT AAGGGACAGG GTCAGGTGTG 10 GTAGGTCAGG CCTGTGATCC CAGGACYI17G GAAGGCCAAG GCAGACAGAT CAGTTGAGCT CAGGAGYTrG AGACCAGCCT GGGCAACATG GGAAAACCCT GTCTCTACAA AATATGCAAA ATATTACCTG GGCATGGTGG CATATGACTG TGGTCCAAGC CACTTGGGGG GCTGAGATGG GAGGATCACT TGAGTACAGG AGGCGGAGGT TGCAGTGAGC CAAGATCTCG CCACTGCAAA CCAGCITrAGG TGACAGAGTG AGAACCTGTC TCAATAAATA AATAAGAAAC GTAAGGGAAA AGGAAATTAA TCTGATCATr GGCAAATGCA TAGTATTTAA AGCCAGGGGA 15 GTAGATGAGA TACTCAAAGT AGGTGAAGAT AAGGAGGCAA TGAAGGCCTA GGACTCTGGT GTACATTTAG ATGGT'TATAA GAGGAATAGA AACTGGCAAA ATAAGTAACA CTGAGCACCC AATGAGGTGG AGAGGAAAGC CAGGAGATGA AGCATCATAG AAGGCAAGAG AAGAAGGGTG TCAAAGAGGC GAGGCAGTCA TCAACTTCTG GGCAGTCAAA TAATATAAGG ACAGAAAAGT GACCATTGGA TTTGGAAATA TGATGAGCAC ThL'GAGTGGA GTGTTGAGAC AGAAGACCAA TT1AGAGTAGA TTGAGGAGAT AACGAGAAAT GAGAAAATGT AACCTGCAAG 20 CACAGACAAT TCTTGAGAGA CTTTJ7CTGTG AAAGGAAACA GACACAGAGT CTTAGCATGT CTTGTCTVTC TATGGGAAAT GTAAATAGT7 TGAGATCAGG GATAGTAThI? TATTCTGCY17 TTTGTACCTC TACATTACCT AGCATAGAGC TAGCTAATGT GCACTTAAGT ATG'I1CTCAA TTCTI7ATCGC CTGAATGACT GGATGGGTGA AAGAATGGAT GGATGGATGG ATGGATGGAT GGAAGGATGG ATGGATGGAT GGAAGACTTC TGATJTGCCA AGAAGAGGAT ACTGGTAGCA GAAATAAAAA CAGCACTGGA GAAAGAAGAG TrAGAYIT TATTCTITGG 25 TGTCAGYI'AG ACAGGAAAGT AAGACA'TAG AAGAGTCCY7 AGATAMTTTA TGTAATTGTT CACTTAGGAT TTTVrAAATGT GATCACTGAT ATTGGACATG 'rTCCTAGTGA AGCATITG GTGTTCACT GGTrGAAGTT AATAACTGTA AAATTATVI'C CCGTTCAGGA CAGAAAAACA GAAAAC FTGA AGCTCCTATI' AGAAAGTTCA AGATTCTCTG GGG'rrC'FAG GATTACTGT TCCCAAAACT CTGTCAAGAA CAAGAAAATG ACCTGTATAC TTAACTGGTC TAGGCAACAG TGGAAAGACA ATTCTCAGAG AAGA'rrrGTT TTAAGAAGAC ACTTTCCATA 30 GGAATCAAAC AATAGC=IC AGTGACTAAC ATGGTA.AGAC ACAGGGTGTr AGCTCTJCC TI'CCAACCTC ATGGCTGTTG TACCTTACCT TTCGACCCCG TGTTCCTGAA ATTGTrAAAT TCATAAACTT ACCAAGGACT AACCAGCCTC TGGGGAATTG CTGTATACLT AGCAAACTrA CAATGGACAT A'I=ATAAGC CATAATGATA ACTGACTAAT AGGAAATACC CTCAACTGAA AATGAGAGAT CATCATTTGC AAATGAGTTC CCYTGCCCAG GCAACTACTG GGGAAAATGT CATGCAAGCA AAATTAATCT TTGAAATCCT CCTITTCCAT TF=PGTGTC 35 'rrCCYI=CC ATAGGCACCA GAAATATCAT GGTGCCTGGA TCTCATCTCT ACAGAAAAAA AAAGTGATT GATAAACTGA 'TrATATTGT GTCCAAATGT GATTGTAM~ TCAAAGATAA CCTAAGGGGA GAATGCTGTC TGGCCCAACA GCAGGCTCTC GACTrFCA'TFT CAGACACTGT GGCCAATGGC TGGGAAACAG GTATGAACAG TAGGTMCTG AGTCCCCTGG AAYFATTCCA TATGTAGC CACCTCCATG ACAGGAAGCC TCCCTACTCT TACTTCCCAG 'ITTGTTCATT CATGGCACCA GGTTGCAGAT TAAAATTTGC TCAGTGACCT TrATCTAAT 40 AATGTGTTAC CTT1C'I1CTCT TAAAAAGTAC AAGGGACAAA TGCTCATGGT ATACTI'TTAG GAGATTGTGG CTCTCTATTA ACAGTATI17A TI1CAACAAAC AYI1TATTGAG CA'ITTATATG TGCATCATGC TAGGGACTGG AACCTAGTAA GTGTAGCACA TATTA TTCA TTAATCCTC ACAACAAACC CATGAGGFTG GTITJ7ATGAT CCCAATTT CAGAAGAAGA AACTGATATI? CAGAACCAGT TAACTAACTG GTTCAAGGTC ATGCAAFI17C TAAGATACAG'AACCAAGAGT CAAAGACATG ATITAAACC AAAGCTITP CTGCTACTCC ACA'rrGCTTC 45 CCTAGGTGAG ATCTGAGGCA 'rTCCGCGAAA AGAGAAGGGT CATAAAGCCA AGGGAAGACA AGC'ITAGGAA AAAAAAGGGA AATGTCCTAA ATAAACAGCT TL1CCTATI1TA CCAGAAACCA CTAG'FTrAAA AATATAATGG GAAAAATCCT A FrCACTTA ACAATG FTAA AAAAAAAAAA GATAGAAGAA ACATAGGGAT AAACTTAACA CATTTGTAGG ATATGTAAAG AAACTAAAAG ATGTTAATAA TGGCCTAAAG AAAAAAAAAC YJ7ACATGTAT GGGGAGATAG ACCATC'ITAC TGGATrCTAA TATTTAATAG TCTAGGTGYI7 CCATrCTCA CCAAATTAAT 50 GTATACA'rfr AATACAATGT CAAACGAAAT ATCTTAGGAA TTGCTTACAA ATITGTCAGAT AATTACAAAG TITACCTGGG AAATATAAGC ATATATGAAG AGTGAATGGG ACCCCACCAC TCCCCCCAAA ACAAAAAAGG TCTGAAAAGG ACAGAAATCA AGGAGAGTCT TGCCTGCCAG ATACAAAATT CTA'ITATAAA GGTGTATTGA TGAAAACAAT TI'AATACTAG TGTAGCAATA GGCAGCAAAG CAATGAAACA GCATAAAAAG ACCAGAACTA TACCTAATTA TGATGAAGAT TTAAGGTATG ATAAACATGA CATAATTCAA ATCAGCAGAA ATTGGCATAG 55 ATAGGGT7AA GACAAATAGC TAATCA'ITAG AGGGGAGGAA GGAAAGGAGG GAGGATAAAA TTAGGTTCCT GCCTTCATCT TACA ITAAAA TAAATTCCAG ATGTA'JTACA TrAAA=II TTTAAAAAAA GAAACCACAA AATACTTGAA GAAAATATAA GTTGTTATAT AGTCTITGA TGGGAATITT TITITfLTC AGAGACAGGG TCTTGCTCTG TCACCTAGCC TAGAGTGCAA TGGCATGATC ATGGCTCACT GCAGCCTTGA ACTCCTGGGC TCAAGTGATC CTCCCAGCTC AGCCCCCCAG GTAGCAGGAA CTACAGGCAT GCGACACCCC ATCCAAC'ITA 60 TITTT'ATTT TTTGTAGAGA CAGGGGTCTI' GC'IMG'IC CCAGGCTTAT CTCGAACTTC TGCCTTCAAG CACCTCAGCC TCCCAAAGAG CTGGGCTGAT GGGACA'TrT TTAACATAGT GCCACATTAC CATAAATGAA AAGCTTGTAA AATACTAAT7 'IAAAACTA ATATATATCA GAAATLTA TAAACAAAGT TAAAAAGCAA ACACAAAAAA TFTGTAGCAC TTATGACAAA TATATGTATA TATATGAATA CAAAAAGAGC CTfTACAAAA CAGTAAGAAA ACAATGAATA CTCCCAATGG AGTATTCAAA ACTAAACTGC TAAAAGCAAT TCAAAACAAA 65 AAACATAAAC TATGCATATA TGTATGTGAA AAAGTTAAC CTTATCAAAG AAGTAAACTC TCAAAGAAAT AAACATCAAA TAAGGAAATA GCCTFICCC ACAAATAACC AAAATCTGTA AGAATACTGA GCTGCGAATG WO 00/62736 PCT/USOO/08020 83 'TTCAGAAAA AAAAAAAAAT CATACACCTA GTFCGGCATG TAATTAATAT AGATCAGAAC ACTTTAAAAA TATTATAGG CCAGGCACGG TGGCTCATGC CTATAATCCC AGCACM1GG GAGGCCAAGG CGGGTGGATC ACCTGAAGTC AGGAG'TITGA GACCATCCTG ACCAACATGG TGAAACCCTG TCTCTACTAA AAATACAAAA ACTAGCCAGG CATGTTGGCG TATGCTGGTA ATCCTGGCTA CTCGGGAGGC TGAGGCAGGA GAATTGCTrG 5 AACCCAGGAG GTGGAGGTTG CAGTGAGCTG ACATTGTGCC ACTGTACTCC AGCCTGGGCA ACAAGAGCAA AACTCTGTCT CAAAAAATAA TAATAAATAA AAATAAAATA TrATATACT CTGACCCATC AATITGTCCA GCATAATTAG GCATGTGTAC AAGGGTTTAC ACACAAGAAT GCCTATTGCA ATA11'GCI TAATGCTAAA AAAAATTGGG GAAAATGCTT TAAAAATATA GATTAAGACT GTACATTGTG GTACAGTCAT ATAATCAATA GTATACAGCT A'FrAT1TATT1 'ECAGCCACT GTCCAAAATA TAGCCTGGCC TAACAACA FT CTGTrAGGAT 10 ACGCAAGCAC CGTGAGGAGA TCAGCTATAA AGTATCAGTG TITCACACCA CTGCTCCTTT GCTAATAACC TTCAATGGCT 'IMAAAGAAG TAAAAAACAA AGGCAAAAT7 CCTrAGTCAG CCCTTAAGAC TCTCTGTTAC TTAGCTCAAA CTACCCTTTT CAACAACACT GCCCTAACCA GGATGAGYIT TTTGCCCCCC TGGAGTACAT TCAGCC1TC CflATCAAAC CTTCCTrAA ATAAGTATCT TCTCCAGGAC CACYI7CACTr TCTTCCCCAA 'TTAGCATTT TCTATATCTC CAGGCCTACC TCTATAAAGC CTGTCCTAAC CACTCAAACC CTAGCTT1T 15 CTCTGAACTG CTAGAAATAT 'I=CTCTCA TTGGCCA'IM AGGTAAAAAG GTLTIACTG TTTATTACCT ACTCAATAAA AATTCTTT FLTGAGACA AGGTCTTACT CTGTCGCCTA GAATGGGGGG AAGTGGTGTG ATCACAACTC ACTGCAGC'IT CTACCTCCCA GCTCAACAGT CCTCCCACCT CAGCCTAGTG AGTAGCTGTG ACTACAGGCA TGTGCCACCA TACCCCACTA CYITCATTT TTTA'TT[ GTGAGATGGA ATCTCACTAT GTTACCCAGG CTGGTCTGCT GATCTCAATT GATCCTCCCA CTGTGGCCTC CCAAAATGCT GGGA'I1ACAG 20 GCATGAGCCA CAATATCTGG CCCCAGTAAG CT1TAAGGC CATI7AACATG AGGAACAGTG TTCTITACAC TATMTATCA GCTAGGGCTT TGCATGGAGT AGGAGTrAG TAAATGCGGT TGATGGG1TA ATCAATGTGT GAAAATATTC AGAGCCACCA AAAACAGATA TTATGTCTAT TCTCATCAAC AATCAAAATr GAGTAAACAG CCAT=CTA ATACAGGAAA CCACAAAACA TTGAATGGTG ACA ITAAAAA ATTCCCCCAG CAGGAGCCAA CCAA1TT= CATCCTGATC CAAGTTAGCA AACTGCAAAA GATAGGAAGC ACTAATGAGT GGAAATTTGA 25 GTAGAAGCAT TTCTrATGAA GGCTGTC'YrG ACTGGATCAC ATTITATTG CTGTTGGAGG TGCCAAATGT GTGTGTTTAT GCTAATCCTC CACCTCAGGC AACACACAGT CAAGGATCCT ACCAAGTGTT ACCGTCAAGT GTCTGTTGGC AGCTCAAGGC CCCAGCGTTG T-rCCC'IGCA CTAGGGAAAA GACATATI7CC AGGTACAAGT ACTCCCACTT TGATGCTACA GAGGAGT7GC TGAAC'=GT GTCATrAATC TCTCTTCGTT AGATCCCAAC CCTG'ITTAAA TCCCACTATC TGCCTACTCT GGGTCTTCAC CAAYI17ACTA GATCATAGTr GGAGAAAATC 30 TACAAAGCCT TGCTCCC1T1T AGATrAAAC AGGTCTCCGT TTAAATTTAG AATTGCTAAC TTCAAGCGGG CCCTTATGCG ACAGTATGCC TGTCAGTCAT ACTACAMC CTCAATTCCA TITCATGTGAC TGCTCCATAC CCTTrCCCTCT CTCTI1CATAC TACTATT1ATC TCTTCCCCCC TCCCTCATI1? 'TAACTGATG ATCTTrGM~C CTA'ITTCTCT GAGAAAATAG AAGCCATCAA AAGAGAGTT CCACAAACTC CTACTGCCTT ATCTAGCCCT GTACCATATA C'ITTGCATfl? CCTCTCATTA CCATGGATGT ACTGCCTATC TGTGCTTCTA TCTAAGGCTA 35 ACCC'I1CCAC TTCAGT=JG AATA'ITATCA GCTCTTACCA ACTCAAGGCC ATTGCTCTAG CAATCTCTC ATJ7CTCTCTC ATTTTCTTCC ATCAAG=Ir CC FT1CTI'C AA ITAACAGA GTAGCTCCTA AAGGGAAAAA AAAGTC'ITCT T =TCAATGC TCATCATCAC TGGCCATCAG AGAAATGCAA ATCAAAACCA CAATGAGATA TCATCTCACA CCAGTTAGAA TGGCAATCAT TAAAAAGTCA GGAAACAACA GGTGCTGGAG AGGATGTGGA GAAATAGGAA CACTTACA CTG'ITGGTGG GACTGTAAAC TAGTTCAACC ATTGTGGAAG ACAGTGTGGC 40 GATTCCTCAG GGATCTAGAA TTAGAAATAC CATI1?GACCC AGCCATCCCA '11ACTGGGTA TATACCCAAA GGATTATAAA CAATGCTGCT ATAAAGACAC ATGCACACGT ATG MITTfG TGGCACTACT CACAATAGCA AAGACTTGGA ACCAACCCAA ACGTCCAACA ATGATAGACT GGATTAAGAA AATGTGGCAC ATATACACCA TGGAATACTA TGCAGCCATA AAAAATGATG AGTTCATGTC CTTTGTAGGG ACATGGAGGA AGCTGGAAAC CATCACTCTC AGCAAACTAT CACAAGGACA AAAAACCAAA CACTGCATGT TCTCACTCAT AGGTGGGAAT 45 TGAACAATGA GAACAC'FrGG ACACAGGAAG GGGAACATCA CCCACTGGGG CCTGT-rGTGG GATGAGGGGA GTGGGGAGGG ATAGCATI'AG GAGATATACC TAATGTTAAA TGATGAG'ITA ATGGGTGCAG CACACCAACA TAGCACATGT ATACATATGT AACAAACCTG CACGTTGTGC ACATGTACCC TAAAACTTAA AGTATAATAA AAAAATATAT ATATATATAT AAAACAACTA AAAATAAATC TTCT7M'CT GCAGGATCAG TCCATCACCA CACACACAGG CTGTGTITA TGTTGTTCCC CAGCTTAAGA GATCGT~rCTC CAGATCCCAC TGCTCCTrCC 50 AGTTGTCACC TCAGTTCTCC ACnrCTT GCTGATAAAC TACTCTAACT AGTTACATAT GA'ITTCTGTC CCCAGGTCCC CTCCCTCAGT TGTITGAAC ATAATCA TT ATATCA'ITA TCAT1TCAC TCTAATTGCA CAACCAAAAA CTCCCTTT YTTAGATGG AGTCTCACTC TGTCACCTAG GCTGGAGTGC AGTGGCATGA TCTCGGCTCA CTCCAACCTC CGCCTCACGG GTTCAAGTGA TCCCCCTGCC TTAGCCTCCT GAATAGCTGG GATTATACAC ATGCACCACC ACACCTGGCT AATTGCTTTG Th1T=GTTG TGTGTGTGTG TGTTTT 55 TITrGGA CAGAGTCTCA CTCTGTTGCC CAGGCTAGAC TGCAGTGGCA TGATCTCAGC TCACTGCAAC CTCCACCTCC TGGGYFCAAG CGATTCTCCT GCCTCAGCCT CCCGAGTAGC TGGGACTACA GGCATGCACC ACCATGCCAG GCTAA T= TTGTATTC AGTAGAGACC AGGTTTCACC ATGTTGGTCA GGCTGGTCTI' GAACTCCTGA CCTCAAATGA TCTGCGCACC TGGACCTCCC AAAGTGCTGG GATTACAGAC TTGAGCTACT GCGCCGGGCT ATTGTGTT 'LTTAGTAAAG ACGGGG TTTC ACCATGTTGT CCAGGCTGGT CTCAAACTCC 60 TGACCTCAAG TGATCCGCTC GCCTCAGGCC CTCAAAGTGC TGGGATTACA GGAGTGAGCC ACCATGCCTG GCCATAAAAC TGCCCTJTGT TAATATGACT GTTGGCCTGC ACATI'GTCAA ATCCAGTGGC ATI'CATCTFA CTCGGCCAAC CTACGGCA117 TGACACTGTC TGTCnI7CCT TCTGTTCCTC TATCTGTITC CAGTATACTG GCCTGGCTTT1 CTTTTACCT CTITATATG CTCTTCCAGT CTCAGGCTCC TrTGGGGA'rr TGAAGGTATG TTGCA'TPTG CTATTCAATG AATAATGACA AGTAATGATC AC FTAAGACA TTAAGTGGTC AGTTCCTA 65 CTAGGATAAA AATAATh7C 'ITCCCAACAT GGGGCATAT7 CCATTTCCAG TCTGACTGTT CTGTGTAATC 'P=GTATTCC TrfGGCAGCCC CT=IATATC AGTTCATCTA CTGTGCAGGA AATFGGACAA ACAMIIGCAC WO 00/62736 PCT/USOO/08020 84 TGGTATAACC AAATACAGTT GAAC1T1GG CTT1GACTCTT AGCTGAACTC ACCAAAAATA ATTTCTGTAA GAGACTGAGA CGTCTACGAG TAGG'TI=C AGAATTAGTA AACATAAATC AAGGATACAC AGGTAGA'IT GAATTTCAGA TAAACAACAA ATAC'TTrr AGTATGTCTA CTGAAATATT TGTATC'ITAT CTGGCAATTC TACCTGGTAC AGAACTAATC CATrCTCTTG AAAGATCTTG ACTCTGTAAT AAGTFTC TG GTGATGGAAG 5 GGAGGTATTr CTGTAATTAG AGTCACTGTC TrCCTCCCAG TIT=7ATCC TGGCCCAGAT CTGCAATGAA CACACGACAG AATCCAGGGG GGATGAAGAT GGGTGC7TTTG CAGGAAAAAA AAATTAAAAA CATCTGAAAA AGCTTrGTA CTAAAAGAAT GTGATCTAAA AAAGAAAGCA GGAGAACTTT CTGTCTGCAC 'TrACATCAG AACAACC117G GCGTCTAGAA GCTGTGCCCT GTGGGAAGTG GTGGTGCTTG GTAAGAGATG CCAGGACCAG TGGTACCCAC TGGGAGCACT GCCAATACCC AGCAAGGAGC ATGGGTGCAC AGTAAGGCAT TGCACTGTGA 10 TI1CAGCATAA AATAACAATA AGGGAACGTC ACGGAGAAAA GGCCAGACTPT CC'ITTGTITA GAATGTGGGA AATGTCTTCT GAAAAATGGT AGTAAAAAAG CATGCTTGGA TGGTCCACTC CAGGCAAAAC TGACTAATCG GGGGTCAGGG ATACAACCCC TGCATCATAT GMIGTI17CT GTITGGGCTGA CATGAGGTTC ACTGTGACCA CTGTGGTTTA ACCCCATAGT CTCCTGGAAA TACAGCCAGG TCAAGAGAGC TCCACATAAA ACATAATCAA AAAAATAAAC TCAAGTTTCC ACTGATCAGC TI=CACAAC TCTTATCCTr TCACTAACTT TGGAGCAAGA 15 TITGAGAATr GGATGGCTAT TTGAGGGCTA TTTCTGCGCT TTAGTTCAAT GTTGTTCT TTCnITATTA GAGAACTATG GTlI=1ATT ATATT7ACAC TAAGTTCT AGGGTACATG TGCACAACGT GCAGATITGT TACACAGGTA TAAATGTGCC ATGTITGG=I GCTGCACCCA TCAACTCGTC AM~ACATrA GGTA'ITTCTC CTAATGCTAT CCCTCCCCCA GTCCCCCACC CCCCGACAGG CCCTGGTGTG TGATGTTCCC CTTCCTGTGT CCAAGTGTI7C TG'ITTATGTG ATAGATTACG 'TrATTGATT TGTGTATGT GAACCAGCCT TGCATCACAG 20 TCACTTGC117 ACAAGAAACA AACACTTCAC AGATGGATCA TTATGTGTGA TAAGTGAAAT CCAAGGATI1T ATGCTCAGAG GTGGGCTTAA CAGGTAGGAA GAGCAGTA'IT TTCCTTCAAC CATGAGTGTA TGCAGGTYT TCTTTTC'T 'TrGAGATGG AGTCTCACTC Y1TACCCAG GCTGGCGCGC AGTGGTGCGA T=TGGCTCA CTGTAACCTC TGCCACCTGG GTT1CAAGCAA TTCTCCTGCC TCAGCCTCCC AAGTGGCTGG GATTACAGGC ACCTGCCACT GTCTCCGGCT AATTGTC 'TTrfAGTAG AGATGGGGTT TCACCATCTT GGCCAGCCTr 25 GTCTT1GAACT CCTGACCTCA TGAATCATCC 'L1TCTCAGCCT CCCAAAGTGC TGGGATTACA GGCATGAGCC ACTGCGCCCA GCCCACAGGT TTI17CAAAGA CTAAACTTAA AAAAAAAAAA AAAATTTCCC AATGAAATAT AAAACTAAAG TGCTAAACTG TGATAGACTG 'TrTACAAGA ATGCCAGM~ TCACAAGTGT CTATAGAACA TGTAATTAG ATAGGTAAGA TGAAATTG ATAATA'TrG ATGGCAAATF TAAACAGGTA TACAACAAAA ATAAAATTCT AAGCCCCTCA ACCAACTGAA TGGACTCC'IT CTCTCAGCCA AAGGAATACC AAAGTAAACC 30 TGAAAAACTA GTITGGCCA GGATrGGGGG TAGGTGGGGG AAGCCCAACA TGACTCA'TrA TTCTCTCCTC CCTTPTGGAAT TCAGGCACAA CTGAATGTCA GCATTGACAC TAAAACACAG ATCU-AAGAC TGACAAGCCA GACTCTTFGT AGCAGAGAGC CAGGCCCTGG AAGAAATCAA GTTATITAT CCCAAAAAAT A=TCTTTGA TATAT=TCA AATGGCCCTG CAAAGCTGTC TCTrGTGGGG AAAATTGACA TGCTGTACAG AATTCCTIrC TCTITCCAAG TITThACTGA TCCAGGAGAG ATTAACTAA GAGGCTAGCA TG T1TT TTT rrr 35 TGAGGCGGAG TCTTGCTCTG TTGCCCAGGC TGGAGTGCAG TGGCGTGATC TCAGCTCACT GCAACCTTCG CCTCCCGGGT TCAAGCGA11 CTCCTGCCTC AGC'ITCCCGA GTAGCTGGGA TTACAGATCC ATGCCACTAT GCCCAGCTAA TITTFGTA Ff T'TrGTAGAG ACAGGG ITTC ACCATGTTGG CCAGGCTAGT ATTGAACTCC TGACCTCGTG ATCCGCCCAC CTCGGCCTCC CAAAGTGCTG GCATTACAGG CGTGAGCCAC CGTGCCCAGC ACAAGACATT TACCGTCTAT TCTCTCTGAA GCTACTATCT AGAGGCTTCA TCAACATAAT AAGACCC FrG 40 GTCTCCACAA CTCCTTATCT TATCCTA'ITA GTITCTACTG ATT1CCAGGTC TrAGATAAT AACAACTCTT TCAACCAATT GCCAATCAGA AAGTC1TGA ATCCACCTAT GA=TAAAAG CCCCACTCCT TCAAGTTATC CCGCCTT1TCT GGACTGAACC AATGTACACC 'ITATATGTGT TGATGGATAT CTGCCTGTAA C'L17CCATI'CC CCTAAAATGT ATAACATCAA GCTGTAACCC AACCACCrrG GGCACATGTT TTCAGGAACT CATGAGACTG TG'TGCAGAC CTTGGTCACT CATATTTGGC TCACAGTAAA CT'rC'ITAAA TAYI7GTATAG AGTTTGGCTT 45 T=TCATT1GA CACAGGAAAA ATAAAGAATT GGAAGGTCTT TCATCAGTCA CTGAGCCAGC TTCATATCTG ACTGAGGTCA TACAGTI7CAG TGATrTGTAG CITI7GCTACT TAGATTGCTA TCCATTATCT AGAAGCATCA GGATCACGTG GGACCTA'ITG GAAATGCAGA C'TTTCCTCCT AGAACCCAGG ACCTrGGAAT A'FrCTrGGCA CATAGTAGGT GCTCAATACA TATTGAACTC CTAGGTGCAA TTCATFTAATT CATGAATTAA TGAA'11AACA CGCTCTCAAA GMITAGTGCT TT=CACAGA CTAGTC'TrC TGCCTCTTAA GCACTCAGCT CACCACGCTT 50 CCAGTCTCAC TCCCCTATITA GTCTGATTAA AATCTGCTTA CATGTGAGTC TGAGATCAAG TGTTrATCTCT TCTGAGAAGT CTTCCCTCAC TGGCCCAAAG GAATFTCTCC TCTATITTAG CACTGTCCCA GTTGACTTGT CATFATTCTA GTCTI1TCA TATTAGTTGT TI=CATATA TATGTTArTA AGGAAACTAG TCATTTCCCC TAATAGAACA AAATTGCTGG CC'T7GGGGT TGGCAATGGA GGGGAGGCTC TT1CTTGAAAA GGGGGAAGAG TGTTCTCCTA ATAITTrCT TACGAGAT11? ATGTTGCTCA TCTITAGCCT TTAGTCCCCC ATTGCCTGCC 55 TACAGTrGGC AGAGACCATC TG FTCTCTCA CTGTCAGGAA CTGTCTCAAT TC'TGAAGITr CAGAGTCAAA AAAGAAGCAA G=ITCCTAG CTCITTGATC AAC'T17CAAA GYM1ACTTC CA'ITTGAAAA TITACTAAGT CACCAGGAGA TGGTITTATAC TGAGAAATAT CCACTCATAC TC FTCCTCTT CAACTTTC'IT CCATATACAC CCTATTACAG GGATATAGTC TTACTCTATA GCTCAAAAGG ATGACCCTAT CAGAAACCTG CACAGTATGT AAAACATTCT CACCAGAGGT TCACTIGTGT A TrCCACCC TAGAATGGAA GCTCTACAAA AGCACAGAAT 60 GTATCAIT AACTI'AGAT TCTATrTCA CACCCAGTGC TTGACACATG ATTTGAAG'IT AATATTIATI' TATCAAGTGA TTGTITTAAA ATCATGACTC ACTCAACAAA G FTATAAGAA TAAGAATAGT G'rrACAGAAT TGGTATACAC AAGCTGACCA TAATCAACAC ACCTATTATC ATT GC GACAGGL17CT CGCTGTCTCA CCCTGGCTGG AGTGGAGTGG CATGACCACG GTTCACTGCA GGTTTGAACT TCCAGGCTCA AGCAATCCTC CCACCTCAGC CTCCCACATA GCTGAGCCCA CAGGTGTGTG CCACCATGTC CAGCTAACT~r TITAATT= 65 TGTAGAGACA GGGTCACCCT ATGTT1GCCCA AGCTGGTC'I17 GAAcTccT-rG GCTAGAGAGA TCCTCCCTCC AAGGTCCCCC AAAATGCTGG GATCTCAGGC AAGAGCCACC ATGCCTGGCC ATAATCAATA CACTTITTAAG WO 00/62736 PCT/USOO/08020 85 AATGCTAGAA TGTTATATCA GATGCATACT TCAGCACTAT CTCAAGCAAA CTGGGGTGTG GGTTATTCTA CATATAAAGT TCAGCAGTGT TGTTCCACAG TCCCAAACTC CAACTGAGGT CAAATGTAGG GTGCAGCAAG GTCACTGGGG CTGTCATCAA GGGCCTCTCC TTGCACTCTT GCCAACCCTG TTTCTrGA'rr GTCTCTACCA CCATGAGTCA CCAGCAATCT CCCACAGTCA CTTGTITAAA AGTrCACAAG TATTGTGTGA AP-FGCAGGCA 5 ACCCCTI1GAC TCCCTGATTG CCTGGTCTTC TTCCTTGGGC TCTACCA'IT TITICCCCA GCACTCM~C TGCTGCTCTA AAYITAATT CATGCAATTC CATATGTGTT1 TCTCTATCAT TCTITCATCTC ITI7CCTCTCC CTTCCATCCA A1TTG TCTGTTGCT TGCTrGCTI'G CTJ7AATACA 3TCTCTY= TCTGAGAAGG CTTGAGTCCA AAACTCTCAG TTACCTGTTG TTCTGTI1'CC CGTrAGrrAA TCTCCGAACC F7CATAAATr AAATCTGACA AAGTCCCCTG ACTAACAAAG GAAATGCACA AGTCACAGTA AAAGGGGCAC ACACAGAACA 10 CAAATAGACC CAGGGTCTTT TCTGTTCATC ACTCAGC'ITr IATAGGAGA TCCAGGAGAA ATGAAGTGGA AAGGGAAGTG TGTTGAG'I1A CTATACAACA CAAGAGTAAA C'TI'CTTATA AGTGGTAA 7 ITTTrACA GGAATAATTG AAAATGGAAA TTACCTTCTC TACTCATAGT AAGTACTCAG TGCG'rrCTTG ATGGGATGAG AATGTGTI17G AGC'ITAGTG TAAGGCAGAA TTCTGTfrAG TCTGCCAGTA T7GGAGAAAA ATAAAACACA AAGGGACTGA CATGTAGGAA GTGGCACCTG GGAGGGTCTC AATTCTTCCT A'TrACAAAAA TGCCCCAGAG 15 AAATAAAAAG CTTGTGTACA TGTTGAGATG GGAGAGTT1CT CTGGCCCCCC TCGCAGGATG TGTGACAGTG GGGTGGCTCT CTGCTGCGCC ACCATGAGCT CAAACCCCTC ATAGGAGGGG GAGCACACAG GCAGGAAGGT GCAGGAGCTG GGCGAGCTCT TTGGGCTCTG GCCCCGTGGT ACTGTCTAGA GGTGGGTGCC TGCAACTCCT GAAAGCCCAA GTGGGCATGT GTTACAGTGC ACTCTrCAG C=TGCTGTC TGCAGCTTAA GCGTTAACCA GCTCAG'ITTC TTCTrGGTAC CCAGGTCCTI' GTCTGGCATC CAGGAAGAAT CAGGTTACAC ATGGACFTGA 20 AGGATGAATG TGGGAGTTTT ATGGAGTGGT GGAGGTGGCT CTCAGTGGGA TGGATGGGGA GCTGGAAGGG GGATGGAGTG GGAAGATGAT ATTCTCCTGG AGTTTGGCTG TCCAGCAGCC GATCTCCTCT CCAGTCGTCC CCAGCCTCTC GACGTTCAGA TGCTCCTCT[ CTCTCC'ITCT CTGCCATGCT GTTCTGCCGT TCATCTGCCT GTCTCTCTCT GGAGCCTGGA ATTrGGGGTT TATATGGTAC ACAATAAGGG GCATGGCAGG CCAAAAGGGA ACTTTAGG TGCAAAAAAC AGGAATGCCT CTrCTCACTT AGGGCTATAG A=~CAGGC TTGAAGGTGG 25 GGCC'TrACC AGCGAACCTG TNITTTCCCTG TCTCCTGTGC ATATCAATGT AATCAAATAC TGGGCTGATC CAGGATGTTT C'TTTAGACCA ATTATGGGTA AAATAA'TrA CATTCAGGTT 'TTATATITG C'TrTTGTCAT TTC'FTMAA GCAATCATGT AAAATATCTA TACGACAGTA ATAGATGATA GCGAACCTAA TTAAAATFAC CAGAAACFTTA AGAATCTCTA ATGAITTCAA CTGTAACTAA GGYPA'ITTCT C'TIATGTTG AACAATGTTG GGAGATAAGA CACAAGAGTT TCTGAAGTAT TTCAGAAACA CAAAGAGGGA GGTTATATAA ATAATATTT 30 TTTCCTACTT TGGGAAAATG AAAGCTAGTC ACAAAGTTAA ACGAGTGGTT A'TH'AATAT TTAAAATACA GGCTTGGATG TATCCTGT TAAAGAAAAT AAAATGCAGA ATATTCAAAA CGTCTGACCA CCCTTCTAAG AAAATGCATC TCTGAGGTAT T ITTCCTTAG AAG'FrATTGT AAAAATCCTG GAGAAGCTTG AACACAGCAA AGCAAACAGG ATGCAGAG'I1 TAATCTGTGG AAAGC'rrAGG GAAGAAAAGC AAATCATTAA AAATAGGTCT TCCTCTGAAG ATI=AAAA CGCAAAGAGG GTGGAATAGC AATGATAATA AAAAAGCTGG CATAGAGAGT 35 GGCACAATTT GCTGTGCCAC TGAGCTGACT GGATGTGTrC TGAA'ITCTA GGCAT'rAGTG TACCTTTCCA CACGCATTCT CC='~AAAA AAAATGCCCA CACACTGAAT ACTTrCA TGCAAITTAA AATAAGCGCA CCATCTAGP'T TACAGAAATT CACTAGAAGT TA'TrATCCT AAAATAGCAG AGATCTAGAA GAA'TrTTGAG CTCTAGGACA TITAGACAC ACAGAAAGAA GAATCTGGAC AAGTCflGAC CAGACATGAC AGAATAGAAA rrCrrrrCC TA'TTATCTC 'FIGAATAAA ATITT'CAGGA TCTTACAGTG GACAAGTrG TTATCTACAC 40 ATTGTGAAGC ACATT1GA'TTT CTCCTCTGTA GCC'ITAGGAA GATCTGAGAG GTGACTGAGC TGATTGAATG ATCCGTGACC GCTCTACTGG GACCAGTAGT AGAAC'1TAC TGGTGGAGAC CTGCTGGAGG T17GAGAGCA GACTPTGAAA ATTACTAGAG CTACACAGAT ACTGTGTGGC TAACTGGAT[ ATG'TrAGAG GC'TrCAGAA CTATGCTGCT GCTGCTGCAG TGTAGCCAGG ACGCACAGAG AACATCTAAG GCTCTTGAAT GGGGCGATAG GGACAGA3TTT CAGCAGCCAT CTGACTTCAG TGCTCATIT GATGC'T~rCC CTGCAGGGTG CAGTGTGCAG 45 TGTGCAGTGT GCAGTGGTGG GAGGCTCACA CAGGAATACT TGCTICTGTA GCCCTAA'TrT CCGG'ITCAAA CTCTGCAT7C ACCTT1GACAG ATTC'TrCCT TGGCCAAAAT TTAGTTAGGC TrCTGGGCTT TCTCTTATGC CCACCTGCAG ACT'IrGGT AAAATCCAGT 1TAGTAAAG AGCTCTGCTA AGTCAGTTTA GCAAGAATCC CCACCTCAAA AGTCACTATC TCCCTCCCTG GTAGTGTCTG GC'ITGTCTT1C AGCGAGAATT CTAYFAGGITr CTGYFAGATT AGAATCCTCC TTACCCTTGA TGCTTCCTCT TAGTAT=1 TCATCCACTG ACTCCTTGAC 50 CCACCTTGCT CCTCGGCTAT AAAT7CCCAC TrGCCCATAC TCTGCAGTTA AGACTAT1T CTCCCCACTA CTGCAAAATC CCA'ITGCCAT GGTCCCTATA CTATCTCAAT GGTAATGAAT AAAGTCTGCC TITACCATGCT TTAACAAGTA ACA'ITGAACC ATITITI1CT TTAACAATCT GCTGCACAAT GAGATTACTA AAACTTTAFT CCAT'ITTGCC ATGCTGGATG TCCTCAATGG AATGGCTC'17 GTGAGCACCA AATCATTGTG AGAAGGAAAA CCCATCTCTT ACAGCCCCCT GTAACGTGAT GTATG'ITACA TGTGATGTAT GTTACATAGT TITTTTITCAT 55 GTFrGATCACT TITGCCCAT TTTCCTATAT C117ATCAGTT1 GGAAGACTGT GGAAGTTTGT AGTACTAAGC CACAAGATGA CTAAGAAGAG TTGAAAGGGC AAGTGGGGCT AAAAACAGAT TrG'TTGAC TrACCCCACC ATTCCCCCTA TCATGGGGCT GAATCTGCCT GGAGGAAGGA GCATCTAT C'TrTGTACTG TGAACCACAC AGTCTAGCAG CAGCACAGCC AAGGCACTTG GGG'TTCATG AGACTAAGTA CATGCAATTC TATTGTAAAG GCTTAAAATA TATACAACTG ACCCTTGAAC AACATGAATT TGAArrGCAT GGTCAGTTAT ACGCAGATTr 60 TCTTCCACCT CTGCCACCCC TGAGACAGTA AGATCAATCA ATCCTCTTCC TCCTACTCCT CAGTCTACTC AAAGATACTT GAAGTCTACT TGAAGATGAC AAGCACAAAG ACAMrATGA TGATCCACTT CCAC'TTAGTG AATAGTAAAT ATGTITCTC YL'CCTCCTAA TITITAACA CTrCTTCTC TCTAGCTTAA rJTA'ITGrrA AGAATACAAT CTATAATACA TATGACATAC AAAATATGTC TTAG'rTGACT G'ITTATG FTA TCTGTAAGGC TTCAGGTCAA GAGTATGCTA TTAGTGGTrA AGTITCGAG GAGTCAAAAG GTGTATGTGG ACTTTCAACT 65 GCAGGGGGGT GGGCACCCCT GCCCCCATGT TGTI7CAAGGG TCAAC'ITTAC TGCCAAAGGC AAGCCTITAC ATCCACT'Tr TCCATCCCAT CAGTAAATGG AAAAAGATAG CTACAGTATC CCTGCGTCAA ATCTTTI WO 00/62736 PCT/US00/08020 86 TTGCAGATCA CAAATI'GGCC ACTCACCTTG CTCTGTGAGG GGTAAAATGC CCCA='TCT TTAGTAATAT FrAAGTTAGA TAATATAA G'ITATAAAGT TGTTCT~GT AATCGTTAAT TGTAAT1TF ACATAGTC TTTCAAACAG AAATAGCATT 31?TGTTAGAT AACCTCCCGT ATAGATGATG AAACTCCTrT TAAGGGCTAT CTGAAF=TA A'rCCTTGAA AAGGCAGAAA TTGGATAGCT AGTAGTCATA AATGTACTGT GGCTTCCCCC 5 AACCATCTGG GCTATATAGA AGCTGCATCC TTGGACTGCA GTAGAGGAGT C'TTACAAAGC ACAGAGCAAC TTrCTCTCCTG GGTrGCGCTA GTTATGATGG CAATITTrAAA TGTGTAC'= TACCCAAAGA AAATCCTFTAT TATCAACAAT CACAATGCCA TCATAACCAT GGTATAAAAA ATTCAAAATG TCCCAGCTGA AGTGGAGGCA AAGACTCAAG TTCATGGAGT CAGAG1TTCC TI7GCTATrCC TCTITICAA ATGACCATTT AGTAAGCACC TGAAGAAAAT ACTATGGACG GCATTGAAAA GTGAAGATAG GTrAATCTr CTCGAAAATC TAATTCTCCA 10 GATGAAACGC TGACACTTAT CCACCCCACA GACCCTATAG CAGATGTGTC ACTGGCCATC ACATI'TGACA CAGAGAAGTC ATAACTCAGT CAGCACAGAG ACA'TrCCAT GAG'I=rCTGA ACCATOGACA GAACGTCGTC TGTGGGACAT GAAAACTGGA ACTTAGAGGA CAGGCACATC TGAGAAATGG GCAGTTTAAA GGCAGAACAT AGCACATATG TGACTGGGTT TTAGAAGCAA A'IMACAAGA CGCACTCTTC TTCATCCTAA ATAATCTGCA ACCAAAGCT'r CCAAAAAAGA CAATIAGGA ATGCAGAGGT GAGGAGTAGG GAGGGGAATG GGATGAGAGA 15 GAGTGGAGAT TAA.TGGTGGG CAGAGCGAGG TrAGAACTr AGTGG1T7CT TCAGGTTCTG AACTGAAATT TGTATACTGT AAAGGCACAA ACACCAYIT TAACAAAAGT GAGGAGGACT TCCTATCTGG TTCAGAAAAT AGGTGAATAA ATAGTACGAA TTATI1AAAAA TAATAATI17C CACTTATACA TAGGAAAC'I1 GATAGGAACC ATGATAAATG CTFAACTCTT AATC'ITCAAG GAACTCTGCT AGGGATATA-A TATTATAAAT CrrGTrTGC AGATGGAGAA ATTGANIT=1 AACCCAAGTT ATCATAACCC TTAAATGATT AAATGATACT GTTACATGAG 20 AAAGCTGCGT ATCTGTTTCC TGGATTTGTA GCCATAA'T7 GTGTCTCAAG TCCC=IrGC TGCCAGCTAT CTTGGGTAGG TGTG'ITCCCT TT1GGGCTGTT TGATACCCCC ACAT117ATCT 'fTflrTFC TCTTTG TTGAGAGAGT CTTTCCCTGT TGCCTAGGCT GGAGGGCAAT GGCGCGATCT CGGCTCACTG CAACCTCCGC CTCCTGGGTT CAAGTGCTTC TCACGATTCT CTTGTCCCAG CCTCTCTAAT AGCTCGGATT ACTGGCATGC ACCACCACGC CCACCTAAT[ TTGTA'TTr AGTAGACAAG GGGTTTCTCC ATGTTGGTCA GGGTGGTCTC 25 AAACTCCTGA CCTCAGGTGA TCTGCCTGCC TI7GGCCTCCC AAAGTGCTGG GATTACAGGT GTGAGCCACC ATGCCTGGCC CCAAATTTAT CnITIAATGCC CCAAATTATC TAGTTCCCAT GACTGGGCTT CTGCFTTGAT CCTTTCTGCA CTrGCTGGAC CCTCTCCCTG GGAAATGAGA TT1GTGTCCTG AGCCCCTAGT TAGAGGCTAT GTCTCTGCTG 'FrCCTGAATG GGCCTCCTGG ATGAGACCTC ATT1AAAAGTC TAATTCTCTT GGAGAATTGA GAGATACCTA TTTGTCTCAA. AATCATTGAA ACCAA FrAAT GTATTATGAG CCTCTATCCA GTGAMEGTA 30 CCTCAATTCC CCAATCCAGC TGTCAAGGCC AA'1TTGTTCT ACCI17ACCTA GTAGGTAAGT CTGGAATTGT AGCTGTGGCA TTTTCAGTAA TGGTACTCTA GG'ITAGCAGT CCCCAACCTT TTTGGCACCA GGGACCAGTT TTGTGGAAGA CAATI1TTCC ATGAAGGGCT GGGCAGGGGA GTGGTCAG GATGAAACTG TTCCACCTCA GATCATCAGG CA'ITAGATTC TCACAAGGAG TGCGCAAGCT AGATCCCTCA CACATGCAGT TCACAATAGG GTGTGCACTC CCATGAGAAT CTAACACCGC TGCTGATCTG ACAGGAGACA GAGCTCAGGC AGTAATACTC 35 A'TrTGCCTAC CGCTCACCTC CTGCCGTGCA GCTCAGTrCC TAACAGGCCA CGGACCAGTA CTGGTCCACG GCGCAGGCAT CAGGGACCCC TGTT1GCTAGG TATAAGCATC TGGCTGCTGC ATGTC'ITCTG TGTAGCTACA TCTGTATGTG TATCTGATGA GATATAAATF ATJ7GATTAT AAATTAC1T C'ITCATATTA GAGTTGTGAA TGAGTATCAC ATATAATIAT ACATAAACTA GGAATATGCT TITTAATAAT GTATATAAGT AAGMhCCTT AACTATGACT I17CATCTTAG, CGTAGTAAGA GGGTGCTAAG AAATATTTGT GATGAAAATA GGCA'FrGGTA 40 GAGTTGAGAC CACTGGGTGA TGAAAGAGTG TAAAGA=~1 AAAGCC'ITCA GATGCTGGTT CAAGGTGAGA AATGTGAFI'G GGAGCAAATC AA FrAACTTC 'ITGAAGTCTr ATAGGGCAGT TATGAATACT TAATGTI'AAC ATATGTAAAG CTCTFCTGCC CTGTATACAG TAAATGCTAG TAGCTA FTA TGATCACTAC TAAAATGGGG ATGACATAAA CCTCATAAGG TITAAGTAT TATGCAAGAT ACTATACAAA GTCCAGTAAA TATCACATTC AATTGAATCC ATGATGTCCG A'rTTrAG CTACTTCCAA GAGAGAAAAA AATGCTGTCA GTTTTACTGT 45 TCTI'ATAGAG AGCAAGGCAG ATCCCAAT7C CCAATGTGGT AACGTGAAAA TITTGCATr TGAATCAACA AAACACTTTC TCCTT17CTTT CCTACTAThT AACAACTGGT AAGTCTATAC TCCCCCAAAT CTGGAAT7CT CCTLTTCT'TAT TC'T1TCCT CCTACCAAGA CCGCAGGATC 1T=ACTTGG CTATAAGGGG TAAACCTCAA GTAGTACAAG TTCTCTGTAT TACTITATA CTCTGTCACA GA'FrCCCTTT G TrTCCTCAT CTCCATGTGA A'ITTAGT'TAA A'rrCTCAGCA TrTCTGATCCT TACTATACAA GGTAAATGAA TATAAAAACA AAACGAAACA 50 AAAACCTC11' CCTAThI'ACA TAAGGCCCCA ACCTAATATI' TAGTGATATA TATTAATGTG AACAAGGAAC TAACGAAGAC TGGGAAGAAA TTCACAGACT TGAGAGAAGA AATGGCAGGA T117CCTGGGA ACAMTTCAT GTAACGTCAA AGGTGGTAAA AGGTCAAATA GAATGAAGAT GGAGAATACC GGAT=Tf ACAAAATGAT TTCCCAGGAG ATCTCATCAA ATGCACGAGG ATACC'ITCTC AGTTTCACCT AGTGAGTAAA AGACTGGTAA CATAGCTCAC TTACAATTTG GATAAACAAA ACTAAACAAA CAACATCAAA AITCAGAAA AAATAATAGC 55 AAAACAGAAA TCAAACACTC AAA'TTTGG TCCTT1CTGT7 TATTTCAMT TGGATACTCA GTGAATGYJ7A 'ATTAACCAGG AAACTTAAAA GTrATTTCAA. FATGAACCT CTI'CAATCCT TCATCAATTA ThITGAGTAT TCTGGTCTTA AAAACATCTC 'ITTCTTCTAC AAACTTCTGA AAGAGATGAA CACCTCCACC TACACCAAAA TAATGTGCTT TGCTGGCCAA AAGTACACGT CCA'TTMAC TI1AACAGTCT AAGGAAAGTC TGGTGCAAAT TACTATAATA ATCTGGGTTG TAAATGGTTT CTGAGGTGAG AATGAGATCA TATITTACAA AAAGTYTITC 60 ACTACTTAGT ACAAGCTI'AC AAAACTCAGA CCACTCACCA GAAAAAAATC GGCATTTATA TAG'I1GTGTr ACTTTTGGTT TCCTGCATCT TTT1CACATCT GGCTCATTrA CATCAT=C 'ITCATCTrCC AAAGTGGAGT TAGCTACTAC ATTAGGTAAG GTTACTI7CAT CAATCACCAT ACTGTTATAA TCTTGAAAGT GAATITCTIT GGACCCTCCC TI1GAATGCAG TTATACCTAG TAAACCTGAT CCACAACCAA GATCCAAGAC TTTTCCCA GCAAAYJTCA C'IMGGCCTT TGTGAAATAA GCCAGGAGGT CAAAGGTACA TTCCCAGAT 'TrAAGCCTC 65 CCTCATAAAC ACCTGTAATC AGATCAGAGT GAGAAGAAAA GC'TI=GAA ACTATGTIT CTCCAGGGAA GTFrCTCTTrC AACAAGATGG =FTCACTAC TGATAACTA ACATGCTGGA AACCTGGTAA TGrTCTATG WO 00/62736 PCT/USOO/08020 87 ACTTTA'TrT CTAACATCTT CTTTAAATCT 'FrAGGCATAG CATGCTCTIT GGCAGCTCTC AAGGAGGGCT G ITTTCCATG TGGCTCCAAG 'ITCCITrGAAC TGCTGGCTGC ACTGAGTGGA CTGTCTGTGT C117GAGAGGG AGCTGCNT TCCATTGACT TATGYICCCA CAAGTGATCC TGAGGCAAGT CAAATTG11TC TGCAGAACAT TTTCTGTCCC TCTCTTCTCC 'TI=GACTT TCTGAGACTG ACAGCTCMI TGAGGAATCC AGGGTCAAAG 5 CTCCATCTCT AATGGGTGTT1 AATrCNIT= CCAGATGGTC TT1CTATAGTG AAATI'AAACT GAAAGGTCAT CCTCTTATTA AATGCACACA ATCTrrAAAT TCAGATTCTT CAACTTCTGG ATAGAATIrTG ATGATACACA CAAATCTGCC TCAATTATTC AATTAG1T= GTTGGGCCCA ATTTCTC'TT AGCAGCTAT ACATGGTAAC AAATA'TTAG AGATAYI17CC AAATGAC T7. AGACGTCT TTGGTCCTCT TCCAAGCAG CTCTGGAAAG AAAAAAAAAA AAAAAAGAAA GAAAATGATG ATTAAAGCAA AATGGCACAT FTCACTAAAG TGTAATATTA 10 AACAGCCACC CCCACCCCTC CCTGTCCCAC CATACAGCTG CT11TCTTA AAAAGTTGTG GGGAAGAGAG AGAGATAAGA GATGGACA CTCATACACA CC'ITAAGGGT TCCAAAGTGG GAGAAGAAAA TCAACTATAA AAACAAACAG AAGAACAACA GCAACCACCA CCACTACCAC CTGGACAAAC ATAAAGTCCA AGATA'FrCAG ACAGGACAGC CTAGCTACTT GCTGTC'TrC AGCTGTCTTG ATITTGTGTCC AACCATATTC ACCCCCTAAG, CTTCCAGAAT AACTI'CACYI7 CTGTC'IIA CAGAAGAGGT GCAGTATFT A TTTGGTAA GTCAGCGTCC 15 CTTTAAAAAC ATGCATAGGT ATGGCCTGGT GTGTGTAAAT TCATCCAAGA CTTCACTCCA AACATrTAGT CGAGAACAGC AGCCCTAAGT GTATAGAAGT GGGGGTAATT TGGCAATAAT TAGTAAAGAC TAATTCGGTG GCAGAGCAAA CGCAAACTAG GGCACTGCAG TAG TrTGGAG AGACCTGTAG AAATAAGAAG CAACTTTATT GAGAATCT-FC TATCTACTGC GCTAGACACT ATACCATCTG CCTCAAYI= CACAGTTCTG GCAAGTGGGA TCTrT7GTTCC CTTTATACAA GATTTACAAT TTGGGGGAGA GGCGGGTCAC CCAGTCCCGC GGCTAGGAAC 20 GCGCCTCTTT CCTCTCCCAT CACGCTGCAA GGCUTGGAGT CACTTCCGGC TGCAGGTCCC GGAACAAATC CGACCCCAGA AGTGGGGACT TCTGGCCCTC ACCTCCCCAT TTGAATGTAA TGTTI'ACAGT GATCCAGACC TGGGGATGCT TGCTTCCCGA CGTGTCCTGG GATCGCGC117 CTGAAAAAGC TCACCTCACA ACGCCTCCTC CGGACCTAAA TCGCGCACCA GTGAGTCGAG TCCTCCAGGG GCTAGAGAAG CCCGACTITTC TFTCCGGCCT TGAGGGACCC GGGCTCACCA AGAAACCAGC CGCCCTCCTC TCTATGG'ITr TGGAGCCGGC GGAGAGCGCG 25 CAAGGGTFGG CGGGACTGCG AG'ITTCCGGT CTGGGCTrG GCGGGTCTGG TJTGAAGCTC TCCTGTTTGA CGAAAGTATG TCTCAGGAAG GTGCGGTCCC AGCTAGCGCG GTrCCCCTGG AAGAATT1AAG TAGCTGGCCA GAGGAGCTAT GCCGCCGGGA ACTGCCGTCC GTCCTGCCCC GACTCCTCAT ATCCTTCCT7 GGTT1GTCACT TCTACCTAGA GAAGGGTGTG GGCGGGTCGC GAACC'ITTCT CTTCTGTCCC TITCAGACCCA CCGCCAGGCT GGGTTATATT ACCGCGGCCT GAACCCCCTC T1FCn7~GT CAGTGAGTGG GATGAAAAGT GAGGGACTGG 30 AGGGGAAGCG ACAACCGTGG TAGAM~AAG TAAGGCTrG GCCCTGGAAA GCCTCGCGGA CGTGTTFCTGA CCCAAGG'I= TAGCAGTGGA TGTGGCG ITT TCTI7CCATTC CTTCYI17CAG TI1TCTGTA CTCGTTGCTT GCAATTAAGT GTAAATACTT TTGCTAGTGG ATAATGGGGG AGGCAAGGAC TGAGACCTGC GGTATGACGA TAGCTCTGGC TC'ITAATAGT TTGAGGTAAA GCGAGATACT CTGAGCTT GTCTCCCGTA AAAAGGGTGG TGAATATGAA TAAGGGC'TrT CTrAGCG'FTA TAAGAATI7AA AGGGCATAGT TCTGTGGTGT GAAATC'ITTA 35 AAAGATG'ITC AGTAAATAAA AATGATLTC CTCCTTCCCC TCTCAGACCT CTITTrCTTC ITrCTTTCTTr ThfTTTT'GAC AAGTI7CTCAC TCCTCTCACC CAGGCTGGAG TCTTTCTGAA AGAGTTCTTC CGC'FrGTrGT TGGCT'PTCAA 'CTGT-rGGATr TGAGGCGCTT AGCGCCTrCT TCGTCCGGGT GCAGCACATIT CTTGATTGGT CTCATGCC'I TGTGGTTGTA AATGTGCCTG GAATCCTAGC CTTFCATGGT AAACCATATG TATATGTATC 'T=CACAA CA'ITTGAGCC CAGCTTTATA CAATTACACT CAAAAGAAAA AAAGTAACCT TCACTTGAGA 40 GAATCTCAAT ACTGCACAAA TA~rGTGCAG CTAAAGCCCT ATGTAATCAC ATAGAAGTCA FCACCTAGG CATTAGCAAA ATCTCAGAAG GTGCCAAAGC CCCCTTIT AG'TI1TGTG TAGGTACAGA ACTGCCGTCT TCAAGGAGTT TCAACTTGAA AACAAATAGC CACCCTCAAA ACATICAAAA ACACTTAAAC TGCGTGCATA ATGTGTGTGA GACATGGTGT TAGGC'TrTGG GAGAACAGAG ACACGGAACG TGATJ'CCTCT TC'I1CCCCAC AAGCTTATAG AGAGACTTCA TTAAGTTGAA AGTCAACATT1 CCCACCTAGC ITTGCACTTC AAACGACATA 45 TTCAAAAAAG CCCAAACTT1C CTCTAGT1T CTFCATCTGA GTAAATGGTI' TCACAAACTG AAACCTTGAA TCCTCTCTGT CTCACACACC CGATCAGTAA GY7CTATT1GT TrCTGA FTCC AAACTATGTC TTGAATCAAT CCGYJ'TATCT CCATCCTCAT TGCTACCACT CTGATTCCAA ACCCTTATCA CCTCTCACTT GGAGTATTAA TAG1TTrCCTFr GThL'CTACTC ATAAYrCATT ATTCCAAAAA AGTTAAGAGG GGAAAAACAT AGATCTCGTC A ITTCCCTTT TTAAACCACT TTACCTTCAA GGTrCCAGGT GATCTAAGCC TI'GCCCTI'CT CTCATACCTA 50 GTTAATTAAC TACACTCTGT TCATGAATAC AT-rAGGCTCA CCTACCTCAA GATC T-=G CTCAGCCTGA TTTG'FTCTCT CAGCC'TPTG CATA'ITTCAT G ITTATGTCT TGGCCCAAAT GTCACY7CCT TAGAGGGGCT TITT7CAGAGC CTTCAATCTT AGGCAGTTCC CCCAAACGCA GTCTTACACT TGTATCACAT TGGCCTGTTC AGTTCTAA AAAGCACATT ACCA'ITAAAA GAAATGCTCT TG TTGCTr GTATATL=C CAC'rrCTACA CATTATGT'rG CAAAGTTCAT AAAGGCAGGA TGTTGA=I~ CTTCACAGCG TTACCCTCAG CACCTAGAAC 55 AGTGCCTGAC ACATAGTAAG CA FTCA~fAA AGGGCTAAAA ATATI17CATG iTTTAAAAAT ACFI7GGGAGT CTAA'FTAGAC AATACTTI T1'CAGCTTAA TGGTAGTATT TTAGCTTCAC TATITAACA AATGAAAAAT T'rGCAATAAA TCTACAATGC CATTACCCCC CAAAAT='~ TTCATG TIT GCATIIACG TATTATT17C CAGGCCTTAC CTGCATGTCT GCATAATCAT AACTGACTAA TTGGAACA GCTGGTAATT A'TrTGAGCTT TACTGAAATr T'ITTCATGAG GCCAATTCTA CCCTACTGAA CTCAAAT1TG AGTTAATGAT GACCTCA1TI 60 TGA'TTGCTGC TGTAAAAAAT AAGA'TI'CGG AAGAGGAATG AA ITC'ITGTA TT1ACTGTGGT AGGACTATGG GTTTT G'ITGTTTGT TTGTITGAG ACGGAGTCTC ACCCTGTCAC CCAGGCTGGA GTGCAGTGGT GCGATCTCAG CTCACAGCAG CCAGGTTCAA GTGATTCTCC 'ITCCTCAGCC TCCCGAGTAG CTGAGATTAC AGGCACGTGC CACCATGCCC GGCTAATTP TTGTATCT AGTAGAGATG GTI17CACCAT GTTGGCCAGG CTGGTCTCGA ACTCCTGACC TCGTGATCCG CCTGCCTCAG CCTCCCAAAG TGCTGGGACT ACAGGCGTGA 65 GCCACCGTGC CCGGCCGGGT TATTCA'nl TCT7ATTAAC ATrCTTTGAT GATrT-rATG GTGTI7GTTAC AGTAAAACAT TI'CTAACAAT TATTCTAACA A'FfA'FCTTG ATGGTGTATA TGAAGAATI' ATTGTCGTGT WO 00/62736 PCT/US00/08020 88 A'ITTGTAAGC TGCTATGTGC AGAAGAATTT CAGTCAAATA AAGT"TGGTAA GATAGGTATG TAAGTAATAT GAAAAAAGAT AGAAGGTGAT GAGTGACTT1A GGTATAAATT AAGTACAATA GAAATGI1GA GGAAAGAAAA ATTTCTTGTA ATAGAAATCG GAAGTACAAA CTGGGCATGG TGGTGTGCAT CTCTAATCCC AGCTCCT-rGA GAGGCTGGTA TGGGAGGATC ACTTAGCCC AGGAGCTTGA GGCTGCAGTG AGGTGTGATC ATGTCACCGC 5 ACTCCATCCT GGGTGACAGC AAGACCGTCT CTCTTT TTT GA GACGGAGTCT CGCCTATGCT GGAGTGCAAT GGCGCGATCT TGGCTCACTG. CAACCTCTGC CTCCCAG'IM CAAGTGATTC TCCTGCCTCA GCCTCCTGAG CAGCTGGGAT TACAGGTGTG CGCCACCATG CCCAGCTAAT TA1T=GTAT 1TTAAGTAGA GACGGGTTCT CACCATACTG GCCAGGCTGG TCTTCAACTC CTGACCTCTT GTTCGCCCAT CTAGGTCTCC CAAAGTGCTG GGATT1ACAGG TGTGAGCCAC CCCAC'ITGGC CCCGAGCGAG ACCCTCTCTC TAAAAAAAAA 10 TAAATAAATA AATCATAAAC CTGTGGATTA T[GTAGCATT G'IMCTCATC TGTCAAAAAT ATrCATGAC TATGCATAGT TTGAAAAGGC AAGTTTGTCC CTGGGCAATT TTCAAAATAT TTCTITAATG TGTTTTCACA ATACTG=hA CCTAATAAAT CTI'AAGITL TAAAAGCAAA ATrAAGCCAG TAATTTGAGT CCAATTCCAA TCTCYFATGA GTCATTGCTI7 AAA=rCAAA AGGGTITAT TTTITMA GG'ITTGTTCT GAGTAATGAA TACCCTA11A CTATGATACT AGTATCTTCC 'FrAA'FrATCC TACTCA'ITGT CTCAACATTC TGACAGTTGG 15 ATTGAGCATA TTCGTAAGTA AAATTGTMT AACTGTATGA TGTACTGA TGT-TAAGGTC CGAGTCCCCA CATACCTCGG TAGATGTGTI7 CTTACAGTL1T TGTATTCCCT TGAAATGTAA CTGTTCTCTA TG'I1ACAGCC TTTATAACCT TCAGTTACTT GAAATGAACA AATTCATTCA AATTCCAGCA CTTAAAAGTT TTAAATTACA TITTTGGATAA ATACCAAAGT GTITGTTGA TGATGTATGT ATAAACAAAT TGTAAATATT AAACGTTAGT TGYI'ACGAYP AGACCTATAT AAAACATGAT ATGCAGTCTA CTGAATAGCT ATCAGCCTCT AACATGTITA 20 GTGTCNL17TA GAAAATGCTT TCTAAATTGC CAAAAGCTGA TTGTCTAGGT GATAACAAAT TTACCAT'I1G GAGGAAGTTG ACTTCTCAT TTTCATGTCT TCATCAGTCT TACTTGATGA GATTCATTCT TCTAGTCAGA AGAGAG'TrA GACTGCTCAG ITTACTCATA TITGAGTTA GCTITTCTAT 'TTAGAG'rrCA CTTGG'FrGTG GAATAYrCAT TTATAAThrG AATCTACG'T~ GTGTAATGGG ACCTAATITI TITCCIT GTVJTGTTG GAGTCTCGT7 YIGTCACCCA GGTI7GGAGTGCAGTGGCGTG ATCTTTGCTC ACTGCAACCT CCACCTTCCA 25 GGTTCAGGTG ATTCTCCTGC CTCAGTCTCC CAAGTAGCTG GGATT1ACAGG CATGCT[rCAC CACGCCTGGC TAATrTrGT A'TTAGTA GAGATGGGGT 'TrCACCATGT TGGCCAGGCT GGTCTCAAAA CTCCTGAGCT CAAGTGATCC TCCTGCCTTG GCCTCCATAA GTGCTGGGAT TACAGGCGTG AGCCGCTGAG CCTGGCCCCA GAGTTTGTTT1 TGTITTGTT TCAAGACAAG ATCTCACTCT AT7GCCCAGG CTGGAGAGCA GTAGTGCGAT CATAGCTCAC TGCAGCCTGA ACTCCTGGGT TCAAGCTATT1 CTCCTGCCTC CATCTTCTAA AGTGCTGTGA 30 TTACAGGTCT GAGCCATGAT GCTTGGCCTG TGTITGTT TG'ITTGTTr GGGGGACAGG GTCTTGCTTr GTCACCAAAA CTGGAGTGTA GTGGTGCGAA CATAGCTAGC TCACTGCAGC CTCCATCTCC CACGCTCAAG CAATCCTCTC ACCTCAGCCT TCCAAGTAGC TGAGACCGCA GGTGCGTGCT ACCATGCGTG GCTAATTTTC TATTTATATA TITrATITI1 GGTAGACATG AGGTCTTGTC ATG'IMCCCA GGTGGTCTrf AACTCCTGGG CTCAGACAGT CCTCCCGCCT CAGCCACCCA AAGTGTTGGG ATTACAGGCG TGAGCCACCA TGCGTGGCAT 35 AATITI1TI AAGTAAATFTA TVITIATC TTGAGTATAG AAGTGATTCA TGTTCATTGT GGAAAATATG AAACATATAG AAAAACAGAA AAGATrACAA AACATCTAAT CTGAAATGGT TAAGAT1TG ATGAGAACAG TCTCATCTCA 'LTCCGTATA TrCCTGCCAG CCTATCCATC A'FrCTTCGTA CATG'ITTATC TACATTAAAA TTGGTGTTAT AYTT7GGAAA C'TrGTrr AACTACATTG TGAACA'Th7 TCATGTITTTA AAATGTCAT[ TTAATGATGG CAGATCCTAT TCAATAGATG TACACACACC TA'TrAACTG GTCCACAATT GTTGGATATG 40 TAGGTCGTI'T CCTTTCTCTC TTEE1TT[ TI17TGGCTA CTACTTAATA GTTTCTCTGT ATAGAATGTG GTATITGAA AGTGTATCAA GCTTrAGATr GGTAGTATTC TTGCNTAA TAAAGGGCAG TGGCCTTTGT TGACTGACAT GACAATATTT TTATAAAATT TG FTATGC TTTACAGAAA TIIGAAAAT TATTGTAGAA ATG'TfITAC CTCATATGAA CCACCTGACA TTGGAACAGA CTTTC'ITC ACAAGTGTTA CCAAAGGTAT AATACTAPI7A CCTGAAAATA CATGTTATAA GGAATCTAGC CTCAGTCTTA GATGAT7AT TAYI'AATTAT 45 GGCTCTCTTr TTCTAATATA TCAAATATAT TCAAAATAAA AATAAGGAGT AAGTAGATCT CATGTGAGAC TATAATGGTG TTAGTGTGAT CATrAGGCAG TTAAAAACTG TTACAGGCTG GGCACGGTGG CTCATGCCTG TAATCCCAGC TCTCTGAGAG GCTGAGGTGG GCAGATCATC TGAGGTCAGG AG I1CGAGAC CACCCATGGT CAACATGATG AAACCTCGTC TCTACTAAAA GTACAAAAAA TrAGCTGGAC ATGGTGGCAG GTGCCTGTAA TCCCAGCTAC TTGGGAGACT GAGACAGGAG AA TTGCTTGA GCCTGGGAGG CGGAGGTTGC ATTGAGTCAA 50 GATCGTGCCA TTGCACTCCA GCCTGGGCAA TAAGAGCGAT GCTCCGTCTC AAAAAAAAAA AAMAAAAAAA AAGAAC'TTAT A'TrrCAGAT TGTGTGGTTC C'ITrACTAAC TGAATITAAA TTA'TrTGTAG TCAAT=AA ATGCTCYI7GT ATITTrAAAGC CACTGTACTC CAGCCTGGGT GACAGAGTGA AACCCTTAAT TCAAAAAAAA AAAAAAAAAA AAGAAAAGCT GGAATATTGG CAAAATCAAG TAACTAAGAG AAAACATTAA ATTCACAGAA TACATJ7ATTA CATI17TAGAT ATATATGGTA TATGYTJ7CT CTGAAAAGCA CAAGCATACC TTTTJTGTTT1 55 TAAATGGAGG GAACTAAAGA TACYI17GGTG CCAAAATGAA ACA'I1ATTTG TAA'I1AATCT CTTATTGAAA TGGGTTT1CTA ACTTTAGCTT TGAATCGTAA TC TrCAAAT FTCTTGTACT CATAGTCACT TGATGATI7CT CTATCTGAAA TA VfCTTAG AATrrGTrCT TGACCACCAG AAAAAGAT7C AACTGTTACA TAGATGAAAA TGGATGTTGA GTGTTAACAG GCCTATGGGA AACAGTATT TCTTTAGCTA CATTGTAT7G TI1GACTGTGT TGCTATrT F ATAATGTrTA GGTCATI'TAA ATT1GTI7AGAA AGATCCAAGT ATJ7AAGATCT AGGGTGGCTA 60 ACTITTCACA GACAAAAAGC TTGTTGTAA GGTCAMTAC TATACCCTTA AJTrCAGGAAG G'ITAGCTrGA A TTGGGTCAA AAGGAAACTG GTTAGAAAAT AAGTGAGTAG TGAATAGGCG ATTCAGTGCA AATTCCTTCC AGAAAATACC CTTGTAAATG ACTGTATGAA TGTGGA TCT TCAAGACAGT CAAATITT1 GTGCGAAAGT AATACT=TA TITITGCAT CTCTAAAACA TGAACTITGA GTGATTr AAAAAAATTG ATGCTATTAA ATAGATrCAA ACCATAGAAA TGGAAAATAA ATCTG=r GGGGCTLTG GGGGGATI1AT GTTGTAAAAA 65 TACCTTCT CTGTATTTTG TGCTTAATTA GGTACAATTG TTAAGCTAGA TGATAGCCTG TGGATGTTAC TAGTGCAAAA TCAAATTATC GTATrGTGTl TTCTCTGTAA AGTITTGTCT TGTCTILCT AGTGATITCT WO 00/62736 PCT/USOO/08020 89 CrrATTCCTG TTrATrACrr GATTT TACAGACTGT GAAATTATTC GATGACATGA TGTATGAATT AACCAGTCAA GCCAGAGGAC TGTCAAGCCA AAATIGGAA ATCCAGACCA CTCTAAGGAA TATITACAA GTAAGTCAAA TGTATTAGAA AGGAGGAGAG AGAGGGAGCT TAAAGAATGT CAAAATITTT ATACTGATAC TGATFAGCTA TGTA'ITCTTA TGTAATGGCC TAATGTrGGA A'rrAAA'IMA TAGAA'FrAAA GACGTGAATA 5 TAGAAACATG AATI7CTGAAT AATAAACTCT TATAAGAAGA GAAGTCATCA AGCTAGCTGA CCCTACCTGT AYTTCAAGG ATATGTGTGG AACACCTGCC ATGTG'TTTG AAG'FTrGTGT TAGTATI7CTA AATGGCTAGA CAGTTGTrTCC AGTATTTGTA GTTCTGATAG ACTAAAGTTC TGTGAAAAGA GGAAGAGACT GTG~rTGTr CATTGCTGTA 'T7GTAGCAC CCAGCATGCT GACTAATACC TrTCAGTGC ACAAAAAATA TATTCTAAGT GAAATrFCCT TCCT-TATTCA CAGACAATGG TGCAGCTCTT AGGAGCTCTC ACAGGATGTG ICAGCATAT 10 CTGTGCCACA CAGGAATCCA TCATrTGGA AAATATTCAG AGTCTCCCCT CCTCAGTCCT TCATATAAT7 AAAAGCACAT TTGTGCATTG TAAGGTGAGT AAAGGTCTAA TTATACTTTG AATGGTATAT AATCAATGTG CATAGGGGCT GAGTAAAATA ATG1TTFGTAT AAGAT1TAC A I1TTAGTCT ATATTATTGA AATAAACTr TCCATAGAAT AAAGAACATG TAAGTAAATA ATTGTTGCAA AAAAAGTGGT 'ITTAAGGAAG TCATTAAAAG TGGCTITTTTG GGG'TTA GTIT7ATCTT ATH'CCCCTC TATAAAGAAA GAAGTI=AA GAATFI'GTGT 15 TGAGACAGAC ACAGGGATCC TGAAATAGYI' ATGTCATG'Tr GCATTGACCA ATATTCAAT~r ACCATTATGA FAGATGTCA GAACTTCCTT TTATAAAGGA AAGTTAATCC TTA1TAGTC CATCTCTACA TGCCAGAGGT AGCCTTGAGG CACAAAAGCT TGCCTAGAAT TI1ATGGGTCA CAGACAG TT TAATATTGCT ATTrG'ITGGG CGAATGAAAA TCACTAGTTA ATTAATACCT CTC'ITTGCTG ATAGGATGCT AAAAATGTCA CGCACCTGGC CTAATGTTAC CCTITI1AG TTCTGTATI'T GCAAGATCAT GGAAGTCAGA AATAATATTF TATACATGCT 20 TGCATCTCT7 GAAGCACACT ATATFTAATG GATG'I1CACT AAACAATGAA TGAATATGTG ATrCAGTAAA 'TTATGATCT CTAATAGTAT GAATTAAAGT AAATGGCT CTTGAGC'Tr GA'TrGT1 TITCTCTCATT TTTA11ATC CGTAATCAGA ATAGTGAATC TGTGTATTCT GGGTGTTTAC ACCTAGT ITC AGACCTTCTC CAGGCTCT[ TCAAGGAGGC CTATTCTCYr CAAAAGCAGT TAATGGAACT GCTGGACATG GTrTGCATGG ACCC=~AGT AGATGACAAT GATGATATrT TGAATATGGT AATAGGTGAG TGAAGAAAAC TP7CTGCTTA 25 GTATATGGTG ACTATAAATC ATGTATCAAT TAAAATTGTC TCTAATGATT CATGTTAT TCTTACTAAT TATGCATTAA AA FTGATTTA AATCTTACCA AATAAATIT TAATCTTGAA NITTGGAATTI TGTAAAA1TT AYTTGGGTA CCTTAACCTA GATTTGCGTA TTTAGTTACT GTAAMTCTC CACAATGATT AACTFATATA ACTIATAAT CTCTGAGGTT GTCCATAT11C AGAGACAATA ACTICACAT TTTTAACC ATAACTGATA TTGAGATGCA GTTTATATTT CCTrFCCAGAA TACATATAAA TACGTGCATA TGTGTATGTA AATATGTCTA 30 TTCTCATATA CATATTATAA TGAAATAACT CATrACAT GTGATGCACT TTATACTAGT TTATITJ-TAT =EAYTTAT TTTGAGA CAGAGTCTCA CTGTGTAGCC CAGGCTGGAG TGCAGTGGCA CAATCTCGGC TCACTGCAAC CTCGCCTCCC GGACTCAAGC GATTCTCCTG CCTCAGCCTC ATGAGTAGCT GGGATTATAG GCGTCCGCCA CCACACCTGG CTAATFTTG TATIT~AGT AGAGACAGGG TrCACCGTG TPrGGCCAGGC TGGTCTTGAA CTCCTGACCT CAGGTAATCC ACCTGCCTCA GCCTCCCAAA GTGCTGGGAT TACAGGCATG 35 AGCCACCGTG CCCAGCCAAT ACTAGTAT 'TITAAAGAA TTGCTGGTCG TAACACACTT CATI1GAT1T ATCACTCATT AATGGAITAT GAACAAGAGT TTGAAAAACA ATATAAAGGC AAAGTTTGCA 'JTCAAAACTr TGGTATAAAG AGAGTAAGTT GGTMTGTGC AGTGTATCAG GCACCTGTL1G CTCTGCAACA CACCACCTCA AAATCTATTT ATTCACTATT TAMTrI1CA TGATTCTGTG AGTCTGCAGT 'ITAGGGTGGG ATGTCCTGAG ACAAC1TTCT CTGATCCACC TGGGGCACTA GCTCACCCAT GTGACTTCAG TGACTTCAT7 CACATCTGGC 40 TGTTGGCAGA GGCAGAAGTA CTTGAGAAAG CCATGTGCAT CATCCAGCAG GTrCACCCTA TCTCAGATAC CTGATGCCAG TGG'TrCAGG GTI1CTAAGA GTAGCAAAAG TGTGAGCAGG TCGCTGTGTG CTAGCACTT TCAAGTTTCT GCTTGCCTTA ATrrATTAT TGTCCCCCGG GCCACAGCAG GTCATAGCGT TTAGCCCAGA GTCATTGTAG AAAAGTGTGG ATTCACAAAG GGCAGTCATT GTGGCCATTT T7ATAAATAA TCTACCACAG ACTGAGTAAA AGCC FrGCAT GAATACCATG GATATTAATT TGAATTCTTC CITTJAGAT rrrCrrrCCT 45 TAGCAATTTG 1T=GTCATT TTGGATTAGA ATTATATCTG TAGAATATT CAGTTATAAT AGGGTACAAC TT17TATrCCA CTGAACATCT TTAG=IIAT TTrAGGTCATC TGGTAGGTAT AAAC'=CAGA AGTPFAATAT7 CAATA'I=AT AAAAACCATT AACAAGTGTG ACACTTAAAT AG'TI'AAATA ATTCTLYGA CACAACTGrr TCCAAGTTGT GTTACGTATT FTAATTCAAT CAAATGTTGA AATTGTTCAG TAGATAGTI TAATTrATAGG AGAAACTCAC CCCCATGACA 'ITTGGATGTC TTAAAAGTTC TGTTATCTTT CTTTGCAGTT ATTCATrrCrr 50 TATrGGATAT CTGCTCTGTT A'TrCCAGTA TGGACCATGC ATrTCATGCC AATACTTGGA AG'TrTATAAT TAAGTAAGTT TGITGTTAT TFT'1ACTIT FAGAAAATG 'rITrCCATAT TCCCCAATCT TAATTAY[CA TGATTC TTA GATTGCATTT AAAACA=1I GTGTGAA TT AATGTTCACT GACACTGCTG TCTGATAATC CAGATA'ITCT ACATGTAGCT CTCAAGCCAA ATTGGACTTC 'I=ACCCTGT GGCCTCTAAA A'ITAAAAAAA ATGTTCTTCC TAGTTAGCTA GTACTFCAGA AATAATGGGC CATGGGCCAG ACTAGAACTTF AACCACTr 55 CTTCTGCTAC TGTTGT1TTAA CCAGCTATCA AGTATCCTAT TTCTAGGATT AGATAAA~rG ATAACTATAA TTAAAACTGA ATATAATCTT TI'CATTAGGT ACTITYAAGT TGTL'CACACT TAA'TrCCATT TGTACAGTAA TTAACTTT CTGAAACTGA AGCATITAA AGGGTCACCA GGGATAGTGC CTGTAGCA1T CATCAGATT C TTAGGGGTGA GAGGAGATGT GGTFGAGATG TAAAAATGGT TAAGAATATC TACITTATAC ACATACATAA AACATTAAAG GTCAGTGTAT 'TTfCAGGTCT TAGGTAC IT TCTTGTACTA CCAGGACATT AAGTTGCCAT 60 TCAGTGGTT1A AGAGTGYFGC CTGGGAGCTG TATCACATGT GCTTAAATCC AYFCTFGAAA TCA'TrTACTC CTTCTGAGCC CTT1GGGCTAT TTGGTTAATT TCTCTGAACG TTAGTTTGCT CATCTGAAAA TGGAAATAAT AATAGCAACT TCTTGACAGG GTTATAGTGA GAATTGAGTT CATCACTGTG AAATGCTTAG AAATGTGCAT GACACATAGT TAATACTCAA GGAATTAGCC ACATCACTAT CATCATCACT GATTATC FTC CACTC'JTACC CTCTJ7CCAGT TCATITCTG CCCAGCAGAA TGATCTITFA AAAAGTAAAT CAGATCATGT TACTCTA FTG 65 CTTGAAGTCT ATCCCA'TrG ATTAAGAATA ACAACCTAAT CCTCTGTGGA TGCTGCCTCC rrCACCAGCC TGTCTCATGC TGCTCTCCCT ACTCTTAGTT CCTCAAACAT ACCAAACTCT CCTGTCCCAG AGTCT=CG WO 00/62736 PCT/USOO/08020 90 TGGTTTITrCC ATCTGCCTAG GATGCTTCTC TCTCCTAT TGTGTACCT7 GCTAACTCCT G=TACTGTC TP'TCAGTTCT CAGCTTAAGA G3TTATATCTT CATGATAACA TrCTTTGATA TCCTTACCCT AAGArrAAGT TAGATTGATA TCCTI'ACCCT AAGAATAAGT TAGATTAGGT CTCTCTA FTG TAGCACCTTA GACTCTGTCA TTGACAAAT CACAGCCCTA ATTAATrAr CTTAAAATTA TITAACATTC TCTCTCATGC TAGACCACAA 5 GTFTCATGCA GGTAAGGCGG AGATJ7GTGTC CATGITTG ACCCCTTTGT CTCCAGGGCC TGGTAGAATG CCTCATACAT AGTAAGAATT1 CAATTAATAT 'TrACACAGA GAAAAAA'ITA GCAACTTATr TAAACAAATA TAACTGCTTC AGAGGTAAAC TGGGCACATC TTAGTTATAT TATGTGATAT ATGATGC'TF 'FGAT-rG'Tr TITrTAAATGT TCTACAAGGT AGATATTGT7 AGAGGTCCTA AGT17ACTTGA TGTGTTACrr GTGGTGATrG TATTCTI1TC lTrrT'CA YI17AGGCAGA GCCTTAAGCA CCAGTCCATA ATAAAAAGCC AGTTGAAACA 10 CAAAGATATA ATTACTAGCT TGTGTGAAGA CATTCTI1C TCC1'CCAT-r CTI'GTrACA. GTI'AGCTGAG CAGATGACAC AGTCAGATGC ACAGGTAAAA TTIGGG.CTAA TAGCATTA AACAGCAACT CTT1ATTPI7CT TTGGCAGTTA GTAAATCTCA 'TTGAATGTC TGGGTCAGTC TA'1TAAGAG GATITTFAATTr TA=TCATT GGGTG'TTT TPGATCTG TGGGA FTATT TATATCCCAT AA'rTAC'Trr CACCCAGAGC ArFGTATTAG ATTCCTAACT GCTGTCAYTG CCTCTGGGGT CTGCCTGGCT CCCTC'ITTGC TTGGTAACTG G'I1?GGTCACA 15 GCATTCTTCT CAGAATCCTT TCATTCTI= CTGCATGAGA ACAAAAATI7C TITGTTCAT A'Tr-GTATAA GATCTGATAT AGCTGCAATC AAT=TGCAT ITTCTTCA CCAACGCATT GCGACCYIA GGGATACAAG TATGTrGTG CATGTATATG TATGTATCAG TCTITAAAT TTGATATAGT CATACA1TTG 'TTTTTAPVI1 GAAAAGTTAG AGTGTTGAAT TGGTATCCCA 'ITTATGAAAC AYI'ATATTCT AAAAA'TrTGT AGTACGATTA TTGGGAATTA TAACTCA LTT TCCTGTAACA CTGTTATACA TAGTACC'I= TGC'ITTCAGA CTAGCCCTCA 20 ATTTTTAThTA ACTATAGTAG TCCTAAATTA TAAGA'ITAAT AGTACTCAGG ACCTAACAGT TATATGTCAT 'G'rrTrr TITIT[GAG ATGGCGTCTC ACTCTGTCAC CCAAGCTGGA GTGCAGTGGT ATGACCT-rGG CTCACTGCAG CCTCTGCCTC ACGGG I1CAA GGGATCGTTC TGCCTTAGCC TCCTGAGTAG CTGGGATTAT AGGCGCCTGC CACCACGCCT GGCTAATIT TTTAGTAGAG ACGGGG'TrC GCCATGT17GG CCAGGCTGGT CTCGAACTCC TGACCTCAGG TGGTCCACCC GCCTTGGCCT CCCAAAGTGC TGGGA'rTACA GGTGTGAGCC 25 ACCGCGCCCA GCCTATATGT AATAATTrA ATGGGACCAT GAAT1TGAATA =rCrrFCCT GAATAGCAAT GACATAGCCC CTTCTAITGT ACATCTGCAA GCTGATACAG GGAATTCCTT1 TGTACCTGCG CTCTTCCCTG CCAGTCAGCT ATGGGGGTGA AAGTGTAGGG GYrCATCCAA GTCCTAAAAC TGGTAGCAAC TCCTAGGGCA GGGCTGATCT GGAAGGACAG ACCCTAGGGG AGGGTGGAAC 'ITTAAAAAGA AGTTCTGAAG GTAGTAAGAA GGAAATGAGG AGTAGTGTI'A GGAAGGGGCT AAC'TTTTC TrC'rrGCTTC TCTT1C'TrTAT CTCACCTGCC 30 CCTCCCCTTG TATCCCTTCT TCCTTICC C'I=CC'rI TTGTCCTCAC 'TrCATTCGTG CATCC'ITTCT GATTCCTC F~ ACC'rrGCTAA AAGGAGAAGT TT1G'I=GGGT ATCCTATATC AATGGCAGGA AGGTrG'rITr CTrCTTTACC TTTATCCTAT AGATTCATAT TCTCAACACC AACCTCCTCC TTCAGTT TCCTTCTTGC TTCTCTTGAC ACCACAGAGT 'FTGCAGCTAG TACTTGGAGA GGAAAATTAA ACAGAGATAC TTGGACCAAG AGTAAGATGA AGAAAGTCTA AACAACAGTA TAGTCTATAG TGGCAAGAGA GAGTATGGGG GCTGCTTAGC 35 CAGGGTGGCT GTACATAAAG TATATCM CA GTTTATATAA ACTGC'TATA GATGGAAATC AGAAAAT-rTA AATT1CTCTTA ACTGTCCAAG AAAATTCTCA TIT=TCAAA TrGGGACTG ATAAATGTGA CCAGTTCTGC FTACTGTCCA TTGCCTGAAA TGGAGCTTTG AGGTGGACTG TATAAT]CT TCAATCYI'AA CTCCAAATrC TGATCAGCGA CGCCCTCTGC TGTTCACTAT TAATATTTAT TT1ACCAATCA AAGTAAAGTA TTrGAAGTT CCTGGCAGTT TT1CACTTGT G TflAGTCC A'I=AGGCTG CTATAACAAA ATCCCTTAAA CTGGGTAAGG 40 GATTATAAAT ATT1AGAAATT TATCTCTCAC AGTTCTGGAA GCTGGGAAGC CCAATATCAA GGCACCAGTA GA'I=GGTGT CTAACGAGGG TGTGCCGTCT GCTTCAAAAA TGGCCCCTrG TTGCTGCATC CTCACTTAGT GCAAGGGGCA AGACAGCTCC CTT1CAACCTC TrTATAAGG GCAC'ITATGT CATTCATGAG GGCAGAGCCC TCATGACTTA ATCACTrCCC CAAAGGCCCC ACCTCTI'AAT AGTATCACAT TGGGTGTfrAG GTGTCTGGGA GGACACCAAT CTrCAAGCCA TATCATCTCA CTTGGAAAAA AGTCAAAATA AAACCAGTAG A'TrTAATrAA 45 TATTACACTA TTTATAGAAG CATGTGATGT ATCATTCC'rr GTATT1AA'ITT CCTGGGGTTG CCGTAACAAG TTACCACAAA CTAGGTGGCT TAAAACAATA GAATTATT CTCTCACA IT TCTAGAGGCA GAAGI'CACA GTGTGTCAAT AGGGCCATGT TCTCTGGAAG GCTTTAGGGG AGAATATATT TCATATC'TrT CTCTITAGCTT CTCGGTGTCA CTGGCAATCC TTrAGC'rrACT TTGGC'ITCT GTGTCTTCAC ATCATC='~ TATAAGAACA CCAGTGATAG TGA'PTAAGGG CATACCTTAC YTrAATATGA CCTCATCTI'A ACTAA'JTATG TCTTCAATAA 50 CCCTA TTCC AAATAAGGCC ACATTCTGAA GTATTGGGAG 'rTAGAACTTA AAGC'rFITrG GGAGGGACAC AGTTCAACCC ATAACAACCC CTAAAATCGA TAT~rAT-FCT CAATTAAGTC TTGAAA'rrGG 'ITTCAAAAAG AGAATAUTCT ATTAGAG'TT TTAATGTATA G'TTTTAACAT ATAGTTCTr AGCCCCCAAT FITfTTTT ITV'lrr TfTTTI TITTGAGAC GGAGTCTCGC TCTGTCGCCC AGGCCGGACT GCGGACTGCA GTGGCGCAAT CTCGGCTCAC TGCAAGCTCC GCTrCCCGGG TLTCACGCCAT TCCCCTGCCT CAGCCTCCCG 55 AGTAGCTGGG ACTACAGGCG CCTGCCACCG CGCCCGGCTA ATT=GT ATITMAGTA GAGACGGGGT 'rrCACCTrGT TAGCCAGGAT GGTCTCGATC TCCTGACCTC ATGATCCACC CGCCTCGGCC TCCCAAA.GTG CTGGGATTAC AGGCGTGAGC CACCGCGCCC GGCCTGCCCC CAATTA3TI7A GTLTCTAT AAACAGGGAA AThTATTTGT GTGGCCCTTA GAACTAATI' AA'TI'CCACT CTAATFCCTA CTTATGTTTA TATAATG=T T'FAGAAA'ITT GTATPrA'TCA GAAAATAAAC ATATACTA'IT GTATCTG FTG CCTACACTTA GATTArrG 60 CCTGCTATAT rTAAATITA T-rAGTAT=T AATTGTTA TT1AAAGAAAG AATGTGCCTG TAATCTCAGC ACTrTGAGA GGCCAAGGCA GAAGGATT1GC TTGAGCCCAG GAG'ITTGAGA CCAGACTGAG CAACACAGGG AGACCCCCAT CTCTACAAAA AATAAAAAAA TTCTCCAGGC CTCATGGCAC ATACCTGTAG TTCTAGTTAC ITGGGAGACT GGGGTGGGAG GATGCATTGA GCCCAGGAGA TTGAGGCTGC AGTGAGCCAT GATCAGGCCA CTGTACTCCA GCTTGGACAA CAGAGTGAGA GCTI'GTCTAG ATAGATAGAT AGATAGATAA TCTAAATAGA 65 TAATAGACAG ATI7ATCTAAA TAGATAATAG ACAGATTATC TAAATAGATA ATAGACAGAT TATCTAAATA GATAATAGAC AGATTATCTA AATAGATAAT AGACAGATTA TCTAAATAGA TAATAGACAG ATTATCTATC WO 00/62736 PCT/USOO/08020 91 TAAATAGATA ATAGATTATC TAAATAGATA ATAGATAGAT AGATTAGATA GATAGATAGA TAGATAGAGC T'rGGACAACA GAGTGAGAGC CTGTCTAGAT AGATAGAAAC AAAGAAAGAA AGAAAGAATG GTGCTCATAT TTTAAAGCAT TGAAAAATGG TCTTCCTTGC TTATATTACC CACACC'FrCT TTGTJ7GGCAT TAAGATGCAA ACTTTGTE= AAACAGTTGA GTAAATCAAA GATGGGACTG TTAAGTrAT7 TGTG FrATTr ACCTGCTITI' 5 TGAAAATGTA AAAATAAAAC TCTAGGTA ATTAGTAGTA TGCTA'IMAG TAATGAAGTA AAGCTAGAGG CTrCGAACAA ATCTTGTGTA ATrCCTCTT GAATGAGAGA GAAAATTTAA AGTAAGCAAA CAAATAAGrT GTGTGTCACC ACTCATTCAG TCA'T1'AACA AGTATITCCA GAGTACTTAT TCTGTGCCAG GAAATGTI'GT AGGTGCCCTC AACAACYI7AG AGTCTAGCCT GAGACACAAG TAAGTAGGTA AWrATTATAG AATGGTATGA TCTrGGAGG ACTGGGTATT GGCTGGCTCA TGGGAGTACA AGATAGGTAC CCAGTGATGA AGTCAGGAAA 10 GG'ITTCTrAT GGTGATATGA TGACGTCTAT GCTGATrATA AGGTCAGTGT AGAATAAACT TTGTGCrTrM AAATI1TGCAT AGCACTGTAT TAGAGAGTTC ATCTrCAAAA TAATCGAAAA GGCTGAGTGT GGTGACCCAT GGCTGTAATC CCAGCACTTr GGGAGGCCGA GGTGGGCAGA TFGCTTGAGC TAGGAG11TCG AGACCAGGCT GGCCAACATG GTGAAACCCC GTCTCTACTA AAAATACAAA AATI'AGCCAG GAGTGATGGT GCGCACCTGT AATGCCAGCT ACTTGGGAGG CTGAGGCAGG AGGATCACTT GAACCCAGGA GGTGGAGGTT1 GAAGTAAGCC 15 GAGGTCATGC CACTGCACTC CAGCCTGGGC AACAGAGTGA GACTCCATCT CAAAAAAAAA AAAAATGATC AAAGAAAGGT GAATTTCAT CTACCCTATI' TCTGCTGAGG AAAATGGACT ATTTTCAAAT A'IITAATA AGGGTCAAAA TGAGGGATC GCATT1TC AAG1TIATG ATTATTAA CTTGTGGAAC AAAAATAAAC CAGAAACCAC CACCTCTCAC GCCAAAGCTC ACACC'ICAG CCTCCAACAT GAAGGTCTCC GCAGCACTFC TGTGGCTGCT GCTCATAGCA GCTGCCTrCA GCCCCCAGGG GCTCGCTGGG CCAGCTTCTG TCCCAACCAC 20 CTGCTGC=E AACCTGGCCA ATAGGAAGAT ACCCCTTCAG CGACTAGAGA GCTACAGGAG AATCACCAGT GGCAAATGTC CCCAGAAAGC TGTGATCTI1C AAGACCAAAC TGGCCAAGGA TATCTGTGCC GACCCCAAGA AGAAGTGGGT GCAGGATTCC ATGAAGTATC TGGACCAAAA ATCTCCAACT CCAAAGCCAT AAATAATCAC CATrITGAA ACCAAACCAG AGCCTGAGTG TFTGCCTAATT TGITTTrCCCT TCTrACAATG CATTCTGAGG TAACCTCATT ATCAGTCCAA AGGGCATGGG 'TPTATTATA TATATATATA 'TTTIT=r AAAAAAAAAC 25 GTATTGCATT TAATL1?ATTG AGGCTTTAAA ACTTATCCTC CATGAATATC AGYFATTT AAACTGTAAA GCTTTGTGCA GATTCMIAC CCCCTGGGAG CCCCAATTCG ATCCCCTGTC ACGTGTGGGC AATGYrCCCC CTCTCCTCTC TTCCTCCCTG GAATCTTGTA AAGGTCCTGG CAAAGATGAT CAGTATGAAA ATGTCATTGT TCTTGTGAAC CCAAAGTGTG ACTCATTAAA TGGAAGTAAA TGT-rG TfA GGAATAC ATGAAGGTCT CCGCAGCACT TCTGTGGCTG CTGCTCATAG CAGCTGCCTT CAGCCCCCAG GGGCTCGCTG GGCCAGCTTC 30 TGTCCCAACC ACCTGCTGCT TTAACCTGGC CAATAGGAAG ATACCCCTTC AGCGACTAGA GAGCTACAGG AGAATCACCA GTGGCAAATG TCCCCAGAAA GCTGTGATCT TCAAGACCAA ACTGGCCAAG GATATCTGTG CCGACCCCAA GAAGAAGTGG GTGCAGGATT1 CCATGAAGTA TCTGGACCAA AAATCTCCAA CTCCAAAGCC ATAA CCACATATTC CCCTCC=If CCAAGGCAAG ATCCAGATGG ATTAAAAAAT GTACCAAGTC CCTCCTACTA GCTTFGCCTCT CTTCTGTT1CT GCT-FGACTTC CTAGGATCTG GAATCTGGTC AGCAATCAGG 35 AATCCCTTCA TCGTGACCCC CGCATGGGCA AAGGC'ITCCC TGGAATCTCC CACACTGTCT GCTCCCTATA AAAGGCAGGC AGATGGGCCA GAGGAGCAGA GAGGCTGAGA CCAACCCAGA AACCACCACC TCTCACGCCA AAGCTCACAC CTTCAGCCTC CAACATGAAG GTCTCCGCAG CACTI7CTGTG GCTGCTGCTC ATAGCAGCTG CCTTCAGCCC CCAGGGGCTC GCTGGGCCAG GTAAGCCCCC CAACTCCTTA CAGGAAAGGT AAGGTAACCA CCTCCAGGCT ACTAGGTCAG CAAGAATCTT TACAGACTCA CTGCAAATTC TCCATTTGAA AAATAGGGAA 40 ACAGG'Th7TG TGGGTGGACA AGAAATGCCT CAACCGTCAC ATCCAGTCAC TGGAAGAGCC AGAACTAGAA AGCTCCCGAG TCT'ITTCCCC ACATTCAAGA GGGCCGCTGG GTGCATCCTT ACCCAGCTAT CCTTACAGTG TTTGGGAATG GGGAATGGCT CTGTCTTACT GTGGGCATGG TGGGCATIT TGGCAGTGGG AGAGAAGGAA AATCTGTTGA TT1AGAAGCTC AGTATGTrAA 'I1CGACTCCA GGACAGCTTT CAGAGACAGT GGCTAAGAGA AGAACGAGGT CCCAGGGGAT CTCTTGAGGT GACTTATIT GACACTCTI1? GGGAAAGTTA TCTAGGAGAT 45 TI'GTTCCATA ACTCAT=C CCATACTCTG GTGACAAA11 TACTGAGTGT ATCGGTCCCA CTGAGCCAGT GCATAGCATG GTAACAAACA GTTCTAAATT ATCAATGACT TAACAGAA'rT AACTAAATTA ACAAAAGTI'A CTTTCTCACT TGTACTAAAT ATCTATAATG TATGGGCTCA GGCTTCTGCA YTTATACTC AGGATTCTAG ACTGATGGAG AAGTrGCCAT GTGGGGGAAC A'ITGATGGAT ACTGTGATAA AGCAGAAGAA AGCTCTCAGG AGTCT1TGCAT AGGCAATGCA CTGTGGCTCA AAAATGACAC CCATCAC=~ GTCTCCTTCT TTATTGATCA 50 AAACTAATTA ATGCCTCCAA CCAAACAAAA GTGGCCAAGA AATGCAAGTC TACCTrGTGT CTCAAAACAG AGGATGGAGA ATATTGGTG AAAATTACCA TGACCATCAC ATGGCCACGT AGGTCTTrTAT AATGACAGAG CTAGCATTTG TCACATrGAC CAAGCTTTGT CCATACAGTC TACAGTAATG ATGAGTCCTC AGTGCACAGG GGAGGATGCT GAAGACACAG GACAGCATCC TCCAGACACA TAAGACTTCA GAGCAGAGGG NI17CTCCCTC CACCTCTCGC AA'VrCCTrGC =LICTCCTAA CTTCC'ITTAC AAAGTCATGC TL1GGAAATGT CTATGTATCA 55 TCATGTGGCT CATTTTf C TCTGTT1CATT ThI1TrCCCC AAAATTCAGC TrFCTGTCCCA ACCACCTGCT GCTITAACCT GGCCAATAGG AAGATACCCC TTCAGCGACT AGAGAGCTAC AGGAGAATCA CCAGTGGCAA ATGTCCCCAG AAAGCTGTGA TGTAAGTAAA TAAAG'I1CAC CCTCCCCTAG ACAAAAAAAT AATGTCTAGG GCACAGAGTC AAGAACTGTG GGAGTCATAG ACTCTGATAG 'TrrGACCTCT ATGGTCCAAT TCArrAATT TCACAAGTGA GTGTTCACTC CCAGCTCCCT GCCTGGGAGA TTGCTGTAGT CATATCAATT TCTTCAAGTC 60 AAGAGCAAAG ATGGTITTAC TGGGCC ITTA AGAGCAGCAA CTAACCCAAG AGTCTCATCC TTCCTCCTCT CCGTAGCAAC CCTh1?GTCCA GGGGCAGATG GTCCTTAAAT A = AGGGTC AAATGGGCAG AA FI=TCAAA AACAATCC31? CCAA ITGCAT CCTGATTCTC CCCACAGCTT CAAGACCAAA CTGGCCAAGG ATATCTGTGC CGACCCCAAG AAGAAGTGGG TGCAGGATTC CATGAAGTAT CTGGACCAAA AATCTCCAAC TCCAAAGCCA TAAATAATCA CCA'T=GA AACCAAACCA GAGCCTGAGT GTTGCCTAAT 'rG'rT=CCC TITCTI1ACAAT 65 GCATTCTGAG GTAACCTCAT TATCAGTCCA AAGGGCATGG GYT=ATTAT ATATATATAT ATATATYIT rTrTAAAAAA AAACGTATTG CATTTAAT ATTGAGGCTT TAAAACTTAT CCTCCATGAA TATCAGTTAT WO 00/62736 PCT/USOO/08020 92 TITTAAACTG TAAAGC =G TGCAGATTCT TFTACCCCCTG GGAGCCCCAA TrCGATCCCC TGTCACGTGT GGGCAATGTT CCCCCTCTCC TCTCTTCCTC CCTGGAATCT TGTAAAGGTC CTGGCAAAGA TGATCAGTAT GAAAATGTCA 'ErGrrCT-rGT GAACCCAAAG TGTGACTCAT TAAATGGAAG TAATGTTGTT TI1AGGAATAC ATAAAGTATG TGCATA=IF ATTATAGTCA CTAGTTGTAA 'TITrGTG GGAAATCCAC ACTGAGCTGA 5 GGGGG GCCAGGTCGC TGTrGGTCCA CGCCGCCCGT CGCGCCGCCC GCCCGCTCAG CGTCCGCCGC CGCCATGGGA GGCCGGAGCC GAGCCGGGGT CGGGCAGCAG CAGGGACCCC CCAGAGGCGG GGCCTGTGGG ACCGCTATGG GCGTGGAGAT CGAGACCATC TCCCCCGGAG ACGGAAGGAC A117CCCCAAG AAGGGCCAAA CGTGTGTGGT GCACTACACA GGAATGCTCC AAAATGGGAA GAAGT-GAT TCATCCAGAG ACAGAAACAA ACCMJCAAG TTCAGAATTG GCAAACAGGA AGTCATCAAA GGTTrGAAG AGGGTGCAGC CCAGATGAGC 10 TTGGGGCAGA GGGCGAAGCT GACCTGCACC CCTGATGTGG CATATGGAGC CACGGGCCAC CCCGGTGTCA TCCCTCCCAA TGCCACCCTC ATC TTrGACG TGGAGCTGCT CAACTT1AGAG TGAAGGCAGG AAGGAACTCA AGGTGGCTGG AGATGGCTGC TGCTCACCCT CCTAGCCTGC TCTGCCACTG GGACGGCTCC TGC3TrTGGG GCTCTTGATC AGTGTGCTAA CCTCACTGCC TCATGGCATC ATCCATrCTC TCTGCCCAAG 'FrGCTCTGTA TGTGTTFCGTC AGTGTTCATG CGAATTCTI'G CTTGAGGAAA CTrCGGTrGC AGATTGAAGC ATTFCAGGTT 15 GTGCATTJ'TG TGTGATGCAT GTAGTAGCCT TTCCTGATGA CAGAACACAG ATCTCTrGTr CGCACAATCT ACACTGCCTT ACCTTCACTT AAACCACACA CACAAGGTGC TCAGACATGA AATGTACATG GCGTACCGTA CACAGAGGGA CTTGAGCCAG TTACC'ITrGC TGTCAC'ITTC TCTCTTATAA A FTCTGTTAG CTGCTCACT AAACAATGTC CTCTTTGAGA AAATGTAAAA TAAAGGCTCT GTGCTTGACA GAATTCGGGC CGCCGCCAGG TCGCTGTTGG TCCACGCCGC CCGTCGCGCC GCCCGCCCGC TCAGCGTCCG CCGCCGCCAT GGGAGTGCAG 20 GTGGAAACCA TCTCCCCAGG AGACGGGCGC ACCTTCCCCA AGCGCGGCCA GACCTGCGTG GTGCACTACA CCGGGATGCT TGAAGATGGA AAGAAATITG ATTCCTCCCG GGACAGAAAC AAGCCCTrTA AGTh17ATGCT AGGCAAGCAG GAGGTGATCC GAGGCTGGGA AGAAGGGGTT GCCCAGATGA GTGTGGGTCA GAGAGCCAAA CTGACTATAT CTCCAGATTA TGCCTATGGT GCCACTGGGC ACCCAGGCAT CATCCCACCA CATGCCACTC TCGTCTTCGA TGTGGAGCTT1 CTAAAACTGG AATGACAGGA ATGGCCTCCT CCCTTrAGCTC CCTGTI'CTTG 25 GATCTGCCAT GGAGGGATCT GGTGCCTCCA GACATGTGCA CATGAGTCCA TATGGAGC'IT TFCCTGATGT TCCACTCCAC 'I=GTATAGA CATCTGCCCT GACTGAATGT GTTCTGTCAC TCAGC'1GC TTCCGACACC TCTG'ITrCCT CTTCCCCTTF CTCCTCGTAT GTGTGTTTAC CTAAACTATA TGCCATAAAC CTCAAG'ITAT TCAYITATT TTGTPITCAT TTTGGGGTGA AGATTCAGTT TCAGTCTTT GGATATAGGT TTCCAATTAA GTACATGGTC AAGTATTAAC AGCACAAGTG GTAGGTFAAC ATTAGAATAG GAATTIGGTGT TGGGGGGGGG 30 GTGCAAGA ATAT1TATT TTAATTIT GGATGAAAYI' IATCTA IT ATATATTAAA CATTCTTGCT GCTGCGCTGC AAAGCCATAG CAGA'ITTGAG GCGCTGITGA GGACTGAATT ACTCTCCAAG TTGAGAGATG TCTTTGGGTT AAATTAAAAG CCCTACCTAA AACTGAGGTG GGGATGGGGA GAGCCTITGC CTCCACCATT CCCACCCACC CTCCC=rAA ACCCTCTGCC TrGAAAGTA GATCATGTF1C ACTGCAATGC TGGACACTAC AGGTATCTGT CCCTGGGCCA GCAGGGACCT CTGAAGCC'JT C'TTGTGGCC 'TTPTT Y7CATCCTGT 35 GGTI'TCTA ATGGACTTTC AGGAA'TrTG TAATCTCATA ACTI'TCCAAG CTCCACCACT TCCTAAATCT TAAGAAC'TrT AATrGACAGT TTCAATTGAA GGTGCTGT GTAGACTTAA CACCCAGTGA AAGCCCAGCC ATCATGACAA ATCCTTrGAAT GT7CTCT[rAA GAAAATGATG CTGGTCATCG CAGCTTCAGC ATCTCCTG'I7 Tr'rGATGCT TGGCTCCCTC TGCTGATCTC AGTrCCTGG CT=~CCTCC CTCAGCCCCT TCTCACCCCT TITGCTGTCCT GTGTAGTGAT ITrGGTGAGAA ATCGTTGCTG CACCCTTCCC CCAGCACCAT TTFATGAGTCT 40 CAAGTTrAT TAT]7GCAATA AAAGTGC'= ATGCCCGAAT TC GCCGCCGCCA TGGGAGTGCA GGTGGAAACC ATCTCCCCAG GAGACGGGCG CACCTTCCCC AAGCGCGGCC AGACCTGCGT GGTGCACTAC ACCGGGATGC TI1GAAGATGG AAAGAAAITff GATTCCTCCC GGGACAGAAA CAAGCCCT= AAGTTATGC TAGGCAAGCA GGAGGTGATC CGAGGCTGGG AAGAAGGGGT TGCCCAGATG AGTGTGGGTC AGAGAGCCAA ACTGACTATA TCTCCAGATT ATGCCTATGG TGCCACTGGG CACCCAGGCA TCATCCCACC ACATGCCACT 45 CTCGTCTTCG ATGTGGAGCT TCTAAAACTG GAATGACAGG AATGGCCTCC TCCCTfAGCT CCCTGTTCTT GGATCTGCCR TGGAGGGATC TGGTGCCTCC AGACATGTGC ACATGARTCC ATATGGAGCT 'ITTCCTGATG T'TCCACTCCA CTTGTATAG ACATCTGCCC TGACTGAATG TGTFCTGTCA CTCAGC=FG CTTCCGACAC CTCTGTTTCC TCTTCCCCTT TCTCCTCGTA TGTGTG'TrA CCTAAACTAT ATGCCATAAA CCTCAAGTT~A TTCA AAGCTTCTAC CCTAGTCTGG TGCTACACTr ACATTIGC'TrA CATCCAAGTG TGGTTA'ITTC TGTGGCTCCT 50 GTTATAACTA TTATAGCACC AGGTCTATGA CCAGGAGAAT TAGACTGGCA TTAAATCAGA ATAAGAGATT TTGCACCTGC AATAGACCTI' ATGACACCTA ACCAACCCCA 'ITATI17ACAA TTAAACAGGA ACAGAGGGAA TAC'TI7ATCC AACTCACACA AGCTGTTC CTCCCAGATC CATGCTIT TGCGTTTATT A'TTrAGA GATGGGGGCT TCACTATGTT GCCCACACTG GACTAAAACT CTGGGCCTCA AGTGATTGTC CTGCCTCAGC CTCCTGAATA GCTGGGACTA CAGGGGCATG CCATCACACC TAGTTCA TT CCTCTA'ITA AAATATACAT 55 GGCTTrAAACT CCAACTGGGA ACCCAAAACA TTCATPTGCT AAGAGTCTGG TGTrCTACCA CCTGAACTAG GCTGGCCACA GGAATTATAA AAGCTGAGAA ATrTrAAT AATAGTAACC AGGCAACATC ATTGAAGGCT CATATGTAAA AATCCATGCC TTCC=lCTC CCAATCTCCA TL1CCCAAACT TAGCCACTGG 7rCTGGCTGA GGCCT'FACGC ATACCTCCCG GGGCTrGCAC ACACCTC'T CTACAGAAGA CACACCTTGG GCATATCCTA CAGAAGACCA GGCTI7CTCTC TGGTCCTTGG TAGAGGGCTA CTrACTGTA ACAGGGCCAG GGTGGAGAGT 60 TCTCTCCTGA AGCTCCATCC CCTCTATAGG AAATGTGTTG ACAATATTCA GAAGAGTAAG AGGATCAAGA C'CTI1GTG CTCAAATACC ACTGTrCTCT TCTCTACCCT GCCCTAACCA GGAGCTTGTC ACCCCAAACT CTGAGGTGAT 'TrATGCCTTA ATCAAGCAAA CTTCCCTCTT CAGAAAAGAT GGCTCA=II CCCTCAAAAG TTGCCAGGAG CTGCCAAGTA TrTCTGCCAAT TCACCCTGGA GCACAATCAA CAAATT1CAGC CAGAACACAA CTACAGCTAC TATTAGAACT ATTATTAF7A ATAAATI'CCT CTCCAAATCT AGCCCCTTGA CTTCGGATIT 65 CACGATTTCT CCCTTCCTCC TAGAAACTTG ATAAGT-JTCC CGCGCTTCCC Tr=rCTAAG ACTACATG11F TGTCATCTTA TAAAGCAAAG GGGTGAATAA ATGAACCAAA TCAATAA=T CTGGAATATC TGCAAACAAC WO 00/62736 PCT/USOO/08020 93 AATAATATCA GCTATGCCAT CTITCACTAT YI-TAGCCAGT ATCGAGTTGA ATGAACATAG AAAAATACAA AACTGAATTC TTCCCTGTAA ATTCCCCGTT TTGACGACGC ACTrGTAGCC ACGTAGCCAC GCCTACTrAA GACAATTACA AAAGGCGAAG AAGACTGACT CAGGCTTAAG CTGCCAGCCA GAGAGGGAGT CATTTCATrG GCGTI'TGAGT CAGCAAAGGT ATJ7GTCCTCA CATCTCTGGC TATTAAAGTA =T1CTGTTG TrG PrrrrCT 5 C'ITGGCTGT 'TrCTCTCAC ATTGCCTTCT CTAAAGCTAC AGTCTCTCCT TrCTITCTT GTCCCTCCCT GGT11TGGTAT GTGACCTAGA ATTACAGTCA GA'TrCAGAA AATGATTCTC TCAT1TTGCT GATAAGGACT GA'rrCG=rr ACTGAGGGAC GGCAGAACTA GTTTCCTATG AGGGCATGGG TGAATACAAC TGAGGCTTCT CATGGGAGGG AATCTCTACT ATCCAAAAT7 ATTAGGAGAA AATTGAAAAT TTCCAACTCT GTCTCTCTCT TACCTCTGTG TAAGGCAAAT ACCTTATrCT TGTGGTGTI7r TTGTAACCTC 'FrCAAACT CA'FrGATrGA 10 ATGCCTGT7C TGGCAATACA TTAGGTTGGG CACATAAGGA ATACCAACAT AAATAAAACA I17CTAAAAGA AG TrACGAT CTAATAAAGG AGACAGGTAC ATAGCAAACT AATTCAAAGG AGCTAGAAGA TGGAGAAAAT GCTGAATGTG GACTAAGTCA TTCAACAAAG 'TrCAGGAA GCACAAAGAG GAGGGGCTCC CCTCACAGAT ATCTGGA'rrA GAGGCTGGCT GAGCTGATGG TGGCTGGTGT TCTCTG11TGC AGAAGTCAAG ATGGCCAAAG TTCCAGACAT GTTTGAAGAC CTGAAGAACT GTTACAGGTA AGGAATAAGA TITATCTCTr GTGATPTAAT 15 GAGGG'TCA AGGCTCACCA GAATCCAGCT AGGCATAACA GTGGCCAGCA TGGGGGCAGG CCGGCAGAGG TTGTAGAGAT GTGTACTAGT CCTGAAGTCA GAGCAGGTTC AGAGAAGACC CAGAAAAACT AAGCATTCAG CATGT'rAAAC TGAGATFACA TTGGCAGGGA GACCGCCATT TT1AGAAAAAT TArII1GAG GTCTGCTGAG CCCTACATGA ATATCAGCAT CAACTTAGAC ACAGCCTCTG TTGAGATCAC ATGCCCTGAT ATAAGAATGG GTITTACTGG TCCATFCTCA GGAAAAC11G ATCTCATrCA GGAACAGGAA ATGGCTCCAC AGCAAGCTGG 20 GCATGTGAAC TCACATATGC AGGCAAATCT CACTCAGATG TAGAAGAAAG GTAAATGAAC ACAAAGATAA AAT-FACGGAA CATATTAAAC TAACATGATG 'TrCCATTAT CTGTAGTAAA TACTAACACA AACTAGGCTG TCAAAATT GCCTGGATAT TTT1ACTAAGT ATAAATT1ATG AAATCTGTTT TAGTGAATAC ATGAAAGTAA TGTGTAACAT ATAATCTA'T TGGTTAAAAT AAAAAGGAAG TGCTTCAAAA CCTTrT CTCTAAAGGA GCTTAACATT CTrCCCTGAA CTTCAMTTAA AGCTCrrCAA T~GTTAGCC AAGTCCAATT TT-rACAGATA 25 AAGCACAGGT AAAGCTCAAA GCCTGTCTT1G ATGACTACTA ATTCCAGATTr AGTAAGATAT GAATrACTCT ACCTATGTGT ATGTGTAGAA GTCCTTAAAT 'FrCAAAGATG ACAGTAATGG CCATGTGTAT GTGTGTGACC CACAACTATC ATGGTCATT1A AAGTACATTG GCCAGAGACC ACATGAAATA ACAACAATTA CATI1CTCATC ATCTIT= GACAGTGAAA ATGAAGAAGA CAGTTCCTCC ATTGATCATC TGTCTCTGAA TCAGGTAAGC AAATGACTGT AATTCTCATG GGACTGCTAT TC'ITACACAG TGG'TrCTTC ATCCAAAGAG AACAGCAATG 30 ACTTGAATCT TAAATAC'TT TGT1TACCC TCACTAGAGA TCCAGAGACC TGTCTTTCAT TATAAGTGAG ACCAGCTGCC TCTCTAAACT AATAG'ITGAT GTGCATTGGC TTCTCCCAGA ACAGAGCAGA ACTATCCCAA ATCCCTGAGA ACTGGAGTCT CCTGGGGCAG GCTTCATCAG GATGTTAGTT ATGCCATCCT GAGAAAGCCC CGCAG3GCCGC TTCACCAGGT GTCTGTCTCC TAACGTGATG TGTTGTGG'I1 GTC'rrCTCTG ACACCAGGAT CAGAGGTTAG AGAAAGTCTC CAAACATGAA GCTGAGAGAG AGGAAGCAAG CCAGCTGAAA GTGAGAAGTC 35 TACAGCCACT CATCAATCTG TGT-rATTGTG 'TrGGAGACC ACAAATAGAC ACTATAAGTA CTGCCTAGTA TGTCTTCAGT ACTGGC'TrA AAAGCTGTCC CCAAAGGAGT AT1TCTAAAA TA'FTTGAGC ATTGTTAAGC AGATITAA CCTCCTGAGA GGGAACTAAT TGGAAAGCTA CCACTCACTA CAATCA'PTGT TAACCTAYIT AGTTACAACA TCTCATTr GAGCATGCAA ATAAATGAAA AAGTC'FrCCT AAAAAAATCA TCTTIATC CTGGAAGGAG GAAGGAAGGT GAGACAAAAG GGAGAGAGGG AGGGAAGCCT AATGAAACAC CAGYI'ACCTA 40 AGACCAGAAT GGAGATCCTC CTCACTACCT CTGTTGAATA CAGCACCTAC TGAAAGAACT TTCATITCCCT GACCATGAAC AGCCTCTCAG CTTCTGTT CCTTCCTCAC AGAAATCCYT CTATCATGTA AGCTATGGCC CACTCCATGA AGGCTGCATG GATCAATCTG TGTCTCTGAG TATCTCTGAA ACCTCTAAAA CATCCAAGCT TACCTTCAAG GAGAGCATGG TGGTAGTAGC AACCAACGGG AAGGTTCTGA AGAAGAGACG GTTGAGTT7A AGCCAATCCA TCACTGATGA TGACCTGGAG GCCATCGCCA ATGACTCAGA GGAAGGTAAG GGGTCAAGCA 45 CAATAATATC 1TrCT=~AC AGTITAAGC AAGTAGGGAC AGTAGAA'1 AGGGGAAAAT TAAACGTGGA GTCAGAATAA CAAGAAGACA ACCAAGCATT AGTCTGGTAA CTATACAGAG GAAAATFAAT TITTATCCTT CTCCAGGAGG GAGAAATGAG CAGTGGCCTG AATCGAGAAT ACT7GCTCAC AGCCATTATT TC'I1AGCCAT ATTGTAAAGG TCGTGTGACT T'ITAGCCTIT CAGGAGAAAG CAGTAATAAG ACCACTTACG AGCTATGTTC CTCTCATACT AACTATGCCT CCTJGGTCAT GTTACATAAT CTITTCGTGA 'I17CAGTTTCC TCTACTGTAA 50 AATGGAGATA ATCAGAATCC CCCACTCATT GGATTGTTGT AAAGATTAAG AGTCTCAGGC 'TrACAGACT GAGCTAGCTG GGCCCTCCTG ACTGTTATAA AGA'I1AAATG AGTCAACATC CCCTAACTTC TGGACTAGAA TAATGTCTGG TACAAAGTAA GCACCCAATA AATGYrAGCT A ITACTATCA 'rrATTATrAT TA'ITTTATI' TTEI17=G AGATGGAGTC TGGCTCTGTC ACCCAGGCTG GAGTGCAGTG GCACAATCTC GGCTCACTGC AAGCTCTGCC TCCTGGG'ITC ATGCCATTCT CCTGCCTCAG CCTCCCGAGT AAGCTGGGAA TACAGGCACC 55 CGCCACTGTT CCCGGCTAAT TrGTATT1 TTAGTAGAG ACGGAGTrC ACCGTGGTCT CCATCTCCTC GTGATCCACC CACCTTGGCC TCCCAAAGTG CCGGGATTAC AGGCGTGAGC CACCGCGCCC GGCCTATTAT TATFTATT'A1 ACTACTACTA CTACCTATAT GAATACTACC AGCAATACTA A=IATTAAT GACTGGATITA TGTCTAAACC TCACAAGAAT CCTACCTT1CT CATITIACAT AAAAGGAAAC TAAGCTCA11 GAGATAGGTA AACTGCCCAA TGGCATACAT CTGTAAGTGG GAGAGCCTCA AATCTAATTC AGTTCTACCT GAGTAAAAAA 60 ATCATGGTI17 CTCCTCCATC CC'LTTACTGT ACAAGCCTCC ACATGAACTA TAAACCCAAT ATTCCTGPET TTAAGATAAT ACCTAAGCAA TAACGCATGT TCACCTAGAA GGYITTAAAA TGTAACAAAA TATAAGAAAA TAAAAATCAC TCATATCGTC AGTGAGAGTT TACTACTGCC AGCACTATGG TATGTrCCT TAAAATCTTT GCTATACACA TACCTACATG TGAACAAATA TGTCTAACAT CAAGACCACA CTATIACAA CTITATATCC AGCT=TCTT ACTTAGCAAT GTATI1GAGGA CATTTTAGAG TGCCCGTT TCACCATTAT AAGCAATGCA 65 ACAATGAACA TCTGTATAAA TAAATATTCA ThTCTCTCAC CC'I=ATTTC CTTAGAATAT ATTCCTAGAA GTAGAATTTC CCAGAGCCAT GAGGATI1TGT GACGCTATlG ATATGTGCCA C=IGCACTC TCTGTGACAT WO 00/62736 PCT/USOO/08020 94 ATATAATTAT TTTTAATGCA TTCATTTTT TCTCAGAGTG CATTCGTTTG AAAACATAGA CGGGAAATAC TGGTAGTCTT CCTTGTCAGT TAGAAACACC CAAACAATGA AAAATGAAAA AGTTGCACAA ATAGTCTCTA AAAACAATGA AACTATTGCC TGAGGAATTG AAGTITAAAA AGAAGCACAT AAGCAACAAC AAGGATAATC CTAGAAAACC AGTTCTGCTG ACTGGGTGAT TTCACTrCTC TTTGCTTCCT CATCTGGATT GGAATATTCC 5 TAATACCCCC TCCAGAACTA TTTTCCCTGT TTGTACTAGA CTGTGTATAT CATCTGTGTT TGTACATAGA CATTAATCTG CACTTGTGAT CATGGITTA GAAATCATCA AGCCTAGGTC ATCACCTTTT AGCTTCCTGA GCAATGTGAA ATACAACTTT ATGAGGATCA TCAAATACGA ATTCATCCTG AATGACGCCC TCAATCAAAG TATAATTCGA GCCAATGATC AGTACCTCAC GGCTGCTGCA T7ACATAATC TGGATGAAGC AGGTACATTA AAATGGCACC AGACATTCT GTCATCCTCC CCTCCTCA TTTACTTATT TATTTATTTC AATCTTTCTG 10 CTTGCAAAAA ACATACCTCT TCAGAGTTCT GGGTTGCACA ATTCTTCCAG AATAGCTTGA AGCACAGCAC CCCCATAAAA ATCCCAAGCC AGGGCAGAAG GTTCAACTAA ATCTGGAAGT TCCACAAGAG AGAAGTTTCC TATCTTTGAG AGTAAAGGGT TGTGCACAAA GCTAGCTGAT GTACTACCTC TTTGGTTCTT TCAGACATTC TTACCCTCAA TITTAAAACT GAGGAAACTG TCAGACATAT TAAATGATTT ACTCAGAT ACCCAGAAGC CAATGAAGAA CAATCACTCT CCTAAAAA GTCTGTTGAT CAAACTCACA AGTAACACCA AACCAGGAAG 15 ATCTTTATTA TCTCTGATAA CATATTTGTG AGGCAAAACC TCCAATAAGC TACAAATATG GCTTAAAGGA TGAAGTTAG TGTCCAAAAA CTTTATCAC ACACATCCAA TTCATGGC GGACATGT TAGTTTCAAC AGTATACATA TITTCAAAGG TCCAGAGAGG CAATTGCA ATAAACAAGC AAGACTTT CTGATTGGAT GCACTTCAGC TAACATGCTT TCAACTCTAC ATTTACAAAT TATTTTGTGT TCTATTTTTC TACTTAATAT TATTCTGCA ATTTTCCCAA TATTGACATC GTGTATGTAT TTGCCATT TAATATCACT AGACAATTCA 20 ATCAGGTTGC TACGTTGGTC CCTTGGGTTT ACTCTAAATA GCTTGATTGC AAATATCTTT GTATATATTA TTGTTTTC TCCTATCTTG TAATTTCTTT GAGCACATCC CAAAGAGGAA TGCCTAGATC AATGGGCACA AATAATTTGA CAGCTCTTAT TAAACATTAT TCTGTAAGTA AAAACTGAAC TACTTTTCAG TATCACTAGC AACATATGAG TGTATCAGCT TCCTAAACCC CTCCATGTTA GGTCATTATG AACTTATGAT CTAACAAATT ACAGGGTCTT ATCCCACTAA TGAAATTATA AGAGATTCAA CACTTATTCA GCCCCGAAGG ATTCATTCAA 25 CGTAGAAAAT TCTAAGAACA TTAACCAAGT ATTTACCTGC CTAGTGAGTG TGGAAGACAT TGTGAAGGAC ACAAAGATGT ATAGAATTCC ATTCCTGACT TCCAGGTATT TACACCATAG GTGGGGACCT AACTACACAC ACACACACAC ACACACACAC ACACACACAC ACCATGCACA CACAATCTAC ATCAACACTT GATTTTATAC AAATACAATG AATTTACTTT CTTTGGTT CTTCTCTTCA CCAGTGAAAT TrGACATGGG TGCTTATAAG TCATCAAAGG ATGATGCTAA AATTACCGTG ATTCTAAGAA TCTCAAAAAC TCAATTGTAT GTGACTGCCC 30 AAGATGAAGA CCAACCAGTG CTGCTGAAGG TCAGTTGTCC TTTGTCTCCA ACTTACCTTC ATTTACATCT CATATGTTTG TAAATAAGCC CAATAGGCAG ACACCTCTAA CAAGGTGACA CTGTCCTCTT TCCTTCCTAC CACAGCCCCC ACCTACCCAC CCCACTCCCA TTGATTCCAG AGGCGTGCCT AGGCAGGATC TATGAGAAAA TATAACAGAG AGTAAGAGGA AAATTACCTT CTC'T CCTTTCCCTG CCTGACCTTA TTCACCTCCC ATCCCAGAGC ATCCATTTAT TCCATTGATC TTTACTGACA TCTATTATCT GACCTACACA ATACTAGACA 35 T7AGGACAAT GTGGCCTGCC TCCAAGAAAC TCAAATAAGC CAACTGAGAT CAGAGAGGAT TAATCACCTG CCAATGGGCA CAAAGCAACA AGCTGGGAGC CAAGTCCCAA AATGGGGCCT GCTGCTTCCA GTTCCCCTCT CTCTGCATTG ATGTCAGCAT TATCCTTCGT CCCAGTCCTG TCTCCACTAC CACTTTCCCC CTCAAACACA CACACACACA ACAGCCTTAG ATGTTTTCTC CACTGATAAG TAGGTGACTC AATTTGTAAG TATATAATCC AAGACCTTCT ATTCCCAAGT AGAATTTATG TGCCTGCCTG TGCTTTTCTA CCTGGATCAA GTGATGTCTA 40 CAGAGTAGGG CAGTAGCTTC ATTCATGAAC TCATTCAACA AGCATTATTC ACTGAGAGCC TTGTATTTTT CAGGCATAGT GCCAACAGCA GTGTGGACAG TGGTGCATCA AAGCCTCTAG TCTCATAGAA CTTAGTCTTC TGGAGGATAT GGAAAACAGA CAACCCAAAC AACCAACAAA AGAGCAAGAT GCTGCAAAAA AAAAAAAAAT GAATAGGGTG CTAAGATAGA GAAAAGTGGG AGAGTGCTAT TTAGACAAAG TGGTAAAAAC AAAGCCCCTT GTGAGATGAG AGCTGCCGAC AGAGGGGGCG GGTCATGGTT GTGGGTTT GGGTAGGACA TTCAGAGGAG 45 GGGGCGGGTC GTGGTTGTGG GTTITTGGGT AGGACATTCA GAGGAGGGGG CGGGTCGTGG TTGTGGGTTT TTGGGTAGGA CATTCAGAGG AGGGGGCGGG TCGTGGTTGT GGGTTTGG GTAGGACATT CAGAGGAGGG GGCGGGTCGT GGTTGTGGGT TTTTGGGACA TTCAGAGGAG TCTGAATGCA CCCAGGCCTA CAACTTCAAG ATGGTAAAGG ACAGCTCCAA GGATCAGAAG AAGCATTCTT GGAACTGGGG CATTTTGAGA AGGAGGAAAA ATATGCAGAG ACTAGTGCTT GCAGAGCTTG CATTTGGATT TCATTTGAGG TACAATGAAA ACCCATTAAT 50 GGGTTTCACA CAGTGCAATG GCCTGACCTC ACTTATATTT CCTAAAATAG AAAACAGATC AGAAGGAAGG CAATAGAGAA GCAGAAAGTC CAATGAGGAG GTTTCACAGC AGTCATGGGG GTGGGGTAAG GAAAAGAAGT GGAAAGAAAC AGACAGAATT GGGTTATATT TTGGAGATAG AACCAACAGA AGGAAGAGGA GAAACAACAT TTACTGAGAA GGGAAAAAGT AGGAGAGGAA TAGGTTTGGG AAATAAATCC TGCTGACATT GGAAACCCCA AGGAAGCCTC AAAAGTATAT TTACTTGCTT TAGATTAAA AGAATAGGAA AGAAGCATCT CAACTTGGAA 55 TTTGAAATCT ATTTTCCAT AAAAGTATTG TFAAATTCTA CTCATACTCA CAAGAAAAGT ACATTCTAAA GAGTATATTG AAAGAGTTTA CTGATATACT TAGGAATTTT GTGTGTATGT GTGTGTGTGT ATGTGTGTGT GTGTGTTTAA CCTTCAATTG TTGACTTAAA TACTGAGATA AATGTCATCT AAATGCTAAA TTGATTTCCC AAAGGTATGA TTTGTTCACT TGGAGATCAA AATGTTTAGG GGGCTTAGAA TCACTGTAGT GCTCAGATTT GATGCAAAAT GTCTTAGGCC TATGTTGAAG GCAGGACAGA AACAATGTTT CCCTCCTACC TGCCTGGATA 60 CAGTAAGATA CTAGTGTCAC TGACAATCTT CATAACTAAT TTAGATCTCT CTCCAATCAA CTAAGGAAAT CAACTCTTAT TAATAGACTG GGCCACACAT CTACTAGGCA TGTAATAAAT GCTTGCTGAA TGAACAAATG AATGAAGAGC CTATAGCATC ATGTTACAGC CATAGTCCTA AAGTGGTGTT TCTCATGAAG GCCAAATGCT AAGGGATTGA GCTTrCAGTCC TTTCTAAC ATCTTGTTCT CTAACAGAAT TCTCTTCTTT TCTTCATAGG AGATGCCTGA GATACCCAAA ACCATCACAG GTAGTGAGAC CAACCTCCTC TTCTTrCTGGG AAACTCACGG 65 CACTAAGAAC TATTTCACAT CAGTTGCCCA TCCAAACTTG TTTATTGCCA CAAAGCAAGA CTACTGGGTG TGCTTGGCAG GGGGGCCACC CTCTATCACT GACTTTCAGA TACTGGAAAA CCAGGCGTAG GTCTGGAGTC WO 00/62736 PCT/USOO/08020 95 TCACTTFGTCT CACTI7GTGCA GTGTTGACAG TTCATATGTA CCATGTACAT GAAGAAGCTA AATCCT'I1AC TGTTAGTCAT TTGCTGAGCA TGTACTGAGC CT~rGTAATTC TAAATGAATG 'ITFACACTCT TTGTAAGAGT GGAACCAACA CTAACATATA ATGTrGTTAT TTAAAGAACA CCCTATATTT TGCATAGTAC CAATCAYTT AATTATTATT CTTCATAACA A=T1AGGAG GACCAGAGCT ACTGACTATG GCTACCAAAA AGACTCTACC 5 CATATTACAG ATGGGCAAAT TAAGGCATAA GAAAACTAAG AAATATGCAC AATAGCAGTT GAAACAAGAA GCCACAGACC TAGGATTTCA TGATTTCATT TCAACTG'IM GCCTTCTGCT T~rAAGTTGC TGATGAACTC TTAATCAAAT AGCATAAG31' TCTGGGACCT CAGTfTATC AT'ITCAAAA TGGAGGGAAT AATACCTAAG CCTI'CCTGCC GCAACAGYJT TTTATGCTAA TCAGGGAGGT CATITGGTA AAATAC'I17CT CGAAGCCGAG CCTCAAGATG AAGGCAAAGC ACGAAATG'rr A'TTrAAT TATTATTTAT ATATGTAT ATAAATATAT 10 TTAAGATAAT TATAATATAC TATATATG GGAACCCCY7 CATCCTCTGA GTGTGACCAG GCATCCTCCA CAATAGCAGA CAGTGTTC TGGGATAAGT AAGMIGAT? TCNI1TAATAC AGGGCA'TrTT GGTCCAAGTT GTGCTT1ATCC CATAGCCAGG AAACTCTGCA ITCTAGTACT TGGGAGACCT GTAATCATAT AATAAATGTA CA'FrAATrAC CTTGAGCCAG TAATTGGTCC GATCTTTGAC TCITrT-GCCA TI'AAACTrAC CTGGGCATTC T'rGTFCA'IT CAA'FrCCACC TGCAATCAAG TCCTACAAGC TAAAATTAGA TGAACTCAAC TTTGACAACC 15 ATGAGACCAC TGTTATCAAA ACTC1TTI CTGGAATGTA ATCAATGTI17 C'FrCTAGGTr CTAAAAATTG TGATCAGACC ATAATG'ITAC ATTATTATCA ACAATAGTGA TTGATAGAGT GTTATCAGTC ATAACTAAAT AAAGCTTGCA ACAAAATTCT CTGACACATA GTTATrCAT7 GCCTTAATCA TTFATIACT GCATGGTAAT TAGGGACAAA TGGTAAATGT TI'ACATAAAT AATTGTA'1TT AGTGTTACTr TATAAAATCA AACCAAGATF TTATA1TLT TCTCCTCTr TGTTAGCTGC CAGTATGCAT AAATGGCATT AAGAATGATA ATATTTCCGG 20 GTTCACTTAA AGCTCATATT ACACATACAC AAAACATGTG TTCCCATCTT1 TATACAAACT CACACATACA GAGCTACATI7 AAAAACAACT AATAGGCCAG GCACGGTGGC TCAGACCTGT AATCCCAGCA CTITGGGAGG ACCAACCTCT TCGAGGCACA AGGCACAACA GGCTGCTCTG GGATTCTCTT CAGCCAATCT TCATTGCTCA AGTGTCTGAA GCAGCCATGG CAGAAGTACC TGAGCTCGCC AGTGAAATGA TGGCTI'AYIA CAGTGGCAAT GAGGATGACT TGTTCITGA AGCTGATGGC CCTAAACAGA TGAAGTGCTC CTTCCAGGAC CTGGACCTCT 25 GCCCTCTGGA TGGCGGCATC CAGCTACGAA TCTCCGACCA CCACTACAGC AAGGGCTI7CA GGCAGGCCGC GTCAGTTGTT GTGGCCATGG ACAAGCTGAG GAAGATGCTG G'rrCCCTGCC CACAGACCTr CCAGGAGAAT GACCTGAGCA CCT7C TrCC CTI'CATC'IT GAAGAAGAAC CTATCTTCTr CGACACATGG GATAACGAGG CTFTATGTGCA CGATGCACCT GTACGATCAC TGAACTGCAC GCTCCGGGAC TCACAGCAAA AAAGCTTGGT GATGTCTGGT CCATATGAAC TGAAAGCTCT CCACCTCCAG GGACAGGATA TGGAGCAACA AGTGGTGrTC 30 TCCATGTCCT TTGTACAAGG AGAAGAAAGT AATGACAAAA TACCTGTGGC CT7GGGCCTC AAGGAAAAGA ATCTGTACCT GTCCTGCGTG TTGAAAGATG ATAAGCCCAC TCTACAGCTG GAGAGTGTAG ATCCCAAAAA TTACCCAAAG AAGAAGATGG AAAAGCGATT TGTCTTCAAC AAGATAGAAA TCAATAACAA GCTGGAA'TrT GAGTCTGCCC AGTTCCCCAA CTGGTACATC AGCACCTCTC AAGCAGAAAA CATGCCCGTC TTCCTGGGAG GGACCAAAGG CGGCCAGGAT ATAACTGACT TCACCATGCA ATFGTGTCT TCCTAAAGAG AGCTGTACCC 35 AGAGAGTCCT GTGCTGAATG TGGACTCAAT CCCTAGGGCT GGCAGAAAGG GAACAGAAAG GYT GAGT ACGGCTATAG CCTGGACTTI' CCTGTTGTCT ACACCAATGC CCAACTGCCT GC=TAGGGT AGTGCTAAGA GGATCTCCTG TCCATCAGCC AGGACAGTCA GCTCTCTCCT TTCAGGGCCA ATCCCCAGCC CTIT7GTTGA GCCAGGCCTC TCTCACCTCT CCTACTCACT TAAAGCCCGC CTGACAGAAA CCACGGCCAC A'ITGGTTCT AAGAAACCCT CTGTCATT1CG CTCCCACA'IT CTGATGAGCA ACCGCTTCCC TATAITTA MAITrA~G'r 40 TG3TIGT=T A'rrCAT-rGGT CTAAMTh1Af CAAAGGGGGC AAGAAGTAGC AGTGTCTGTA AAAGAGCCTA GTTTAATA GCTATGGAAT CAATTCAATT TGGACTGGTG TGCTCTCTI1? AAATCAAGTC CTITAAYI7AA GACTGAAAAT ATATAAGCTC AGATTATI1?A AATGGGAATA TTTATAAATG AGCAAATATC ATACTGYTCA ATGGTTCTGA AATAAACTTC TCTGAAG AGAAAGAAAG AGAGAGAGAA AGAAAAGAAA GAGGAAGGAA GGAAGGAAGG AAGAAAGACA GGCTCTGAGG AAGGTGGCAG TI7CCTACAAC GGGAGAACCA GTGGTTAATT 45 TGCAAAGTGG ATCCTGTGGA GGCANNCAGA GGAGTCCCCT AGGCCACCCA GACAGGGCTT YrAGCTATCT GCAGGCCAGA CACCAAATTT CAGGAGGGCT CAGTGTTAGG AATGGATTAT GGCTTATCAA ATT1CACAGGA AACTAACATG TTGAACAGCT 'ITTAGATrTC CTGTGGAAAA TATAACT7AC TAAAGATGGA GTTCTTGTGA CTGACTCCTG ATATCAAGAT ACTGGGAGCC AAATTrAAAAA TCAGAAGGCT GCTTGGAGAG CAAGTCCATG AAATGCTCTTr TCCCACAG TAGAACCTAT 'ITCCCTCGTG TCTCAAATAC 'TGCACAGAG GCTCACTCCC 50 TT1GGATAATG CAGAGCGAGC ACGATACCTG GCACATACTA ATTTGAATAA AATGCTGTCA AATI'CCCATT CACCCATTCA AGCAGCAAAC TCTATCTCAC CTGAATGTAC ATGCCAGGCA CTGTGCTAGA CT-rGGCTCAA AAAGATTrCA G'ITTCCTGGA GGAACCAGGA GGGCAAGGTI1 TCAACTCAGT GCTATAAGAA GTGTTFACAGG CTGGACACGG TGGCTCACGC CTGTAATCCC AACAMI7GGG AGGCCGAGGC GGGCAGATCA CAAGGTCAGG AGATCGAGAC CATCCTGGCT AACATGGTGA AACCCTGTCT CTACTAAAAA TACAAAAAAT TAGCCGGGCG 55 TTGGCGGCAG GTGCCTGTAG TCCCAGCTGC TGGGGAGGCT GAGGCAGGAG AATGGTGTGA ACCCGGGAGG CGGAACTTGC AGGGGGCCGA GATCGTGCCA CTGCACTCCA GCCTGGGCGA CAGAGTGAGA CTCTGTCTCA AAAAAAAAAA AAAAGTGTTA TGATGCAGAC CTGTCAAAGA GGCAAAGGAG GGTGTI7CCTA CACTCCAGGC ACTGTTCATA ACCTGGACTC TCATTCATTC TACAAATGGA GGGCTCCCCT GGGCAGATCC CTGGAGCAGG CAC'ITTGCTG GTGTCTCGGT TAAAGAGAAA CTGATAACTC TTGGTATTAC CAAGAGATAG AGTCTCAGAT 60 GGATATCTr ACAGAAACAA TATrCCCACT TTTCAGAGTT CACCAAAAAA TCATITAGG CAGAGCTCAT CTGGCAYI7GA TCTGG11TCAT CCATGAGATT GGCTAGGGTA ACAGCACCTG GTCTTGCAGG GTT1GTGTGAG CTJ7ATCTCCA GGGTTGCCCC AACTCCGTCA GGAGCCTGAA CCCTGCATAC CGTATGTrCT CTGCCCCAGC CAAGAAAGGT CAATTCTC CTCAGAGGCT CCTGCAATTG ACAGAGAGCT CCCGAGGCAG AGAACAGCAC CCAAGGTAGA GACCCACACC CTCAATACAG ACAGGGAGGG CTATrGGCCC T[rCATTGTAC CCATTTATCC 65 ATCTGTAAGT GGGAAGATTC CTAAACTI'AA GTACAAAGAA GTGAATGAAG AAAAGTATGT GCATGTATAA ATCTGTGTGT C=CCAC'TT GTCCCACATA TACTAANT AAACATTCTT CTAACGTGGG AAAATCCAGT WO 00/62736 PCT/US00/08020 96 ATTTrAATGT GGACATCAAC TGCACAACGA TTGTCAGGAA AACAATGCAT A=TGCATGG TGATACATfT GCAAAATGTG TCATAGTTTG CTACTCCTI'G CCC'ITCCATG AACCAGAGAA TI1ATCTCAGT TFATrAGTCC CCTCCCCTAA GAAGCTITCCA CCAATACTCT TTTCCCCTI' CCTTTAACTT GATTGTGAAA TCAGGTATTC AACAGAGAAA =IICTCAGCC TCCTACTTCT GCTIMGAAA GCTATAAAAA CAGCGAGGGA GAAACTGGCA 5 GATACCAAAC CTCTTCGAGG CACAAGGCAC AACAGGCTGC TCTGGGATrC TCTTCAGCCA ATCTTCATTG CTCAAGTATG AC'TrFAATCT TCCT7ACAAC TAGGTGCTAA GGGAGTCTCT CTGTCTCTCT GCCTCTrTGT GTGTATGCAT ATTCTCTCTC TCTCTCTCTT TCTTTCTCTG TCTCTCCTCT CCTTCCTCTC TGCCTCCTCT CTCAGCTTTT TGCAAAAATG CCAGGTGTAA TATAATGC'I1 ATGACTCGGG AAATAI17CTG GGAATGGATA CTGCTI7ATCT AACAGCTGAC ACCCTAAAGG YFAGTGTCAA AGCCTCTGCT CCAGCTCTCC TAGCCAATAC 10 ATTGCTAGTT GGGG'TrGGT TL'AGCAAATG CYITCTCTA GACCCAAAGG ACTTCTC1T CACACATTCA ITCATTTACT CAGAGATCAT TTCTTTGCAT GACTGCCATG CACTGGATGC TGAGAGAAAT CACACATGAA CGTAGCCGTC ATGGGGAAGT CACTCA=I1 CTCC'TTrA CACAGGTGTC TGAAGCAGCC ATGGCAGAAG TACCTGAGCT CGCCAGTGAA ATGATGGCTT ATTACAGGTC AGTGGAGACG CTGAGACCAG TAACATGAGC AGGTCTCCTC 'ITTCAAGAGT AGAGTGTTAT CTGTGCTTGG AGACCAGA'JT '1TTCCCCTAA AY[GCCTCTT 15 TCAGTGGCAA ACAGGGTGCC AAGTAAATCT GA'TrTAAAGA CTACTITCCC ATTACAAGTC CCTCCAGCCT TGGGACCTGG AGGCTATCCA GATGTGTTGT TGCAAGGGCT TCCTGCAGAG GCAAATGGGG AGAAAAGAYT CCAAGCCCAC AATACAAGGA ATCCC TTGC AAAGTGTGGC TTGGAGGGAG AGGGAGAGCT CAGATTTTAG CTGACTCTGC TGGGCTAGAG GT-rAGGCCTC AAGATCCAAC AGGGAGCACC AGGGTGCCCA CCTGCCAGGC CTAGAATCTG CCTTCTGGAC TGTICTGCGC ATATCACTGT GAAACTT1GCC AGGTG1TTCA GGCAGCYITG 20 AGAGGCAGGC TGTrGCAGT TTCTTATGAA CAGTCAAGTC 'ITGTACACAG GGAAGGAAAA ATAAACCTGT 'I1AGAAGACA TAATTGAGAC ATGTCCCTGT T'TrATTACA GTGGCAATGA GGATGAC'ITG '11C'I1TGAAG CTGATGGCCC TAAACAGATG AAGGTAAGAC TATGGGTTTA ACTCCCAACC CAAGGAAGGG CTCTAACACA GGGAAAGCTC AAAGAAGGGA GTTCTGGGCC ACTTTGATGC CATGGTATF TGTTTTAGAA AGACTTTAAC CTCTTCCAGT GAGACACAGG CTGCACCACT TGCTGACCTG GCCACTrGGT CATCATATCA CCACAGTCAC 25 TCACTAACGT TGGTGGTGGT GGCCACACTT GGTGGTGACA GGGGAGGAGT AGTGATAATG FTCCCATITC ATAGTAGGAA GACAACCAAG TCTI'CAACAT AAA'ITrGAT? ATCCTT~AA GAGATGGATI' CAGCCTATGC CAATCACTTG AGYI7AAACTC TGAAACCAAG AGATGATCTT GAGAACTAAC ATATGTCTAC CCCTVI'TGAG TAGAATAGTT Tm1GCTACC TGGGGTGAAG C TrATAA.CAA CAAGACATAG ATGATATAAA CAAAAAGATG AATI'GAGACT TGAAAGAAAA CCATrCACTT GCTG'ITTGAC CTTGACAAGT CAYTI'ACCC GCMfGGACC 30 TCATCTGAAA AATAAAGGGC TGAGCTGGAT GATCTCTGAG ATTCCAGCAT CCTGCAACCT CCAGTTCTGA AATATT=CA GTI7GTAGCTA AGGGCATTTG GGCAGCAAAT GGTCATT CAGACTCATC CTTACAAAGA GCCATGTTAT ATrCCTGCTG TCCCTTCTGT TTTATATGAT GCTCAGTAGC CTTCCTAGGT GCCCAGCCAT CAGCCTAGCT AGGTCAGTTG TGCAGGTTGG AGGCAGCCAC TITCTCTGG C ITTA1TTA TTCCAGTL17G TGATAGCCTC CCCTAGCCTC ATAATCCAGT CCTCAATCTT GTAAAAACA TATITCTITA GAAGTTAA 35 GACTGGCATA ACTTC'I1GGC TGCAGCTGTG GGAGGAGCCC ATTGGCTTGT CTGCCTGGCC 1TGCCCCCC ATTGCCTCTT CCAGCAGCTT GGCTCTGCTC CAGGCAGGAA A FrCTCTCCT GCTCAACTIT C1TTGTGCA C TTACAGGTC TCTTTAACTG TC TTCAAGC CTTTGAACCA TTATCAGCCT TAAGGCAACC TCAGTGAAGC CTAATACGG AGCTTCTCTG AATAAGAGGA AAGTGGTAAC A=PCACAAA AAGTACTCTC ACAGGAYJTG CAGAATGCCT ATGAGACAGT GTT1ATGAAAA AGGAAAAAAA AGAACAGTGT AGAAAAATTG AATACTTGCT 40 GAGTGAGCAT AGGTGAATGG AAAATGTI7AT GGTCATCTGC ATGAAAAAGC AAATCATAGT GTGACAGCAT TAGGGATACA AAAAGATATA GAGAAGGTAT ACATGTATGG TGTAGGTGGG GCATGTACAA AAAGATGACA AGTAGAATCG GGATTTATTC TAAAGAATAG CCTGTAAGGT GTCCAGAAGC CACAFTCTAG TCTTGAGTCT GCCTCTACCT GCTGTGTGCC CTTGAGTACA CCCTTAACCT CC'FrGAGC'IT CAGAGAGGGA TAATCTTT AYITTYTT ATITATITI GTI=G'TT G3T=GT1T GTTITATGAG ACAGAGTCTC ACTCTG11GC 45 CCAGGCTGGA GTGCAGTGGT ACAATC FrGG CTTACTGCAT CCTCCACCTC CTGAGTTCAA GCGATTCTCC TTCCTCAGTC TCCTGAATAG CTAGGATTAC AGGTGCACCC CACCACACCC AGCTAAT1TT TGTA'TITA GTAGAGAAGG GG3TTCGCCA TGTTGGCCAG GCTGGTTITG AAGTCCTGAC CTAAATGATF CATCCACCTC GGCTTCCCAA AGTGCTGGGA TTACAGGCAT GAGCCACCAC GCCTGGCCCA GAGAGGGATG ATC1TTAGAA GCTCGGGATT C'ITTCAAGCC C'ITTCCTCCT CTCTGAGCTT TCTACTCTCT GATGTCAAAG CATGGTTCCT 50 GOCAGGACCA CCTCACCAGG CTCCCTCCCT CGCTCTCTCC GCAGTGCTCC 'FrCCAGGACC TGGACCTCTG CCCTCTGGAT GGCGGCATCC AGCTACGAAT CTCCGACCAC CACTACAGCA AGGGCTI7CAG GCAGGCCGCG TCAGTTGTTG TGGCCATGGA CA AGCTGAGG AAGATGCTGG TT1CCCTGCCC ACAGACCTTC CAGGAGAATG ACCTGAGCAC CTTCTTrCCC TTCATC'TrG AAGAAGGTAG TTAGCCAAGA GCAGGCAGTA GATCTCCACT TGTGTCCTCT TGGAAGTCAT CAAGCCCCAG CCAACTCAAT TCCCCCAGAG CCAAAGCCCT YFAAAGGTAG 55 AAGGCCCAGC GGGGAGACAA AACAAAGAAG GCTGGAAACC AAAGCAATCA TCTCTTTAGT GGAAACTATT CT7AAAGAAG ATCTTGATGG CTACTGACAT TTGCAACTCC CTCACTC'IT CTCAGGGGCC 'ITCACTTAC ATTGTCACCA GAGGTI7CGTA ACCTCCCTGT GGGCTAGTGT TATGACCATC ACCATITAC CTAAGTAGCT CTGTTGCTCG GCCACAGTGA GCAGTAATAG ACCTGAAGCT GGAACCCATG TCTAATAGTG TCAGGTCCAG TGTL1CTTAGC CACCCCACTC CCAGCTTCAT CCCTACTGGT GTGTCATCA GACITTTGACC GTATATGCTC 60 AGGTGTCCTC CAAGAAATCA AA'TPTGCCA CCTCGCCTCA CGAGGCCTGC CC317CTGATT TTATACCTAA ACAACATGTG CTCCACA1TTT CAGAACCTAT CTT1CTTCGAC ACATGGGATA ACGAGGCTTA TGTGCACGAT GCACCTGTAC GATCACTGAA CTGCACGCTC CGGGACTCAC AGCAAAAAAG CTTGGTGATG TCTGGTCCAT ATGAACTGAA AGCTCTCCAC CTCCAGGGAC AGGATATGGA GCAACAAGGT AAATGGAAAC ATCCTGG'ITT CCCTGCCTGG CCTCCTGGCA GC'VrGCTAAT TCTCCATG'IT TTAAACAAAG TAGAAAG11A A'TrTAAGGCA 65 AATGATCAAC ACAAGTGAAA AAAAATATTA AAAAGGAATA TACAAACT' GGTCCTAGAA ATGGCACA'rr TGATrGCACT GGCCAGTGCA TTTGTTAACA GGAGTGTGAC CCTGAGAAAT TAGACGGCTC AAGCACTCCC WO 00/62736 PCT/US00/08020 97 AGGACCATGT CCACCCAAGT CTCTGGGCA TAGTGCAGTG TCAATTCTTC CACAATATGG GGTCA'TrTGA TGGACATGGC GTAACTGCCT GTGGGT-rCTC TCTJCCTGTT GTTGAGGCTG AAACAAGAGT GCTGGAGCGA TAATGTGTCC ATCCCCCTCC CCAGTCTTCC CCCCTTGCCC CAACATCCGT CCCACCCAAT GCCAGGTGGT TCCTITGTAGG GAAA=PAC CGCCCAGCAG GAA=TATAT CTCTCCGCTG TAACGGGCAA AAGTI11CAAG 5 TGCGGTGAAC CCATCATrAG CTGTGGTGAT CTGCCTGGCA TCGTGCCACA GTAGCCAAAG CCTCTGCACA GGAGTGTGGG CAACTAAGGC TGCTGACTTT GAAGGACAGC CTCACTCAGG GGGAAGCTAT TTGCTCTCAG CCAGGCCAAG AAAATCCTGT TTC'ITGGAA TCGGGTAGTA AGAGTGATCC CAGGGCCTCC AATTGACACT GCTGTGACTG AGGAAGATCA AAATGAGTGT CTCTC'I=GG AGCCAC'IMC CCAGCTCAGC CTCTCCTCTC CCAG'ITTCTT CCCATGGGCT ACTCTCTGTI? CCTGAAACAG TT1CTGGTGCC TGATI1CTGG CAGAAGTACA 10 GCTT1CACCTC TTTCCTTTCC TTCCACATTG ATCAAGTT1GT TCCGCTCCTG TGGATGGGCA CA'ITGCCAGC CAGTGACACA ATGGCTTCCT TCCTTCCTTC CTTCAGCATT TAAAATGTAG ACCCTCTTTC ATTCTCCGTT CCTACTGCTA TGAGGCTCTG AGAAACCCTC AGGCC'=GA GGGGAAACCC TAAATCAACA AAATGACCCT GCTATT1GTCT GTGAGAAGTC AAGTIATCCT GTGTCTTAGG CCAAGGAACC TCACTGTGGG rrCCCACAGA GGCTACCAAT TACATGTATC CTACTCTCGG GGCTAGGGGT TGGGGTGACC CTGCATGCTG TGTCCCTAAC 15 CACAAGACCC CCTTC'ITTCT TCAGTGGTGT TCTCCATGTC C'=GTACAA GGAGAAGAAA GTAATGACAA AATACCTGTG GCCTTGGGCC TCAAGGAAAA GAATCTGTAC CTGTCCTGCG TGTTrGAAAGA TGATAAGCCC ACTCTACAGC TGGAGGTAAG TGAATGCTAT GGAATGAAGC CCTTCTCAGC CTCCTGCTAC CAC'I1AL1CC CAGACAATTC ACCTTCTCCC CGCCCCCATC CCTAGGAAAA GCTGGGAACA GGTCTATG ACAAGTTIFG CATTAATGTA AATAAArTIA ACATAATTTT TAACTGCGTG CAACCTTCAA TCCTGCTGCA GAAAATTAAA 20 TCATITGCC GATGTI7ATTA TGTCCTACCA TAG'ITACAAC CCCAACAGAT TATATATrGT TAGGGCTGCT CTCATTT1GAT AGACACCTTG GGAAATAGAT GACTL1AAAGG GTCCCA117AT CACGTCCACT CCACTCCCAA AATCACCACC ACTATCACCT CCAGCTTT1CT CAGCAAAAGC TTCATCCA AG'I1GATGTC A317CTAGGAC CATAAGGAAA AATACAATAA AAAGCCCCTG GAAACTAGGT ACTTCAAGAA GCTCTAGCYI' AATITCACC CCCCCAAAAA AAAAAAATTC TCACCTACAT TATGCTCCTC AGCATTTGGC ACTAAGYIT AGAAAAGAAG 25 AAGGGCTCTT TTAATAATCA CACAGAAAGT TGGGGGCCCA G'FrACAACTC AGGAGTCTGG CTCCTGATCA TGTGACCTGC TCGTCAGT CCTTTCTGGC CAACCCAAAG AACATC1TC CCATAGGCAT CTFTGTCCCT TGCCCCACAA AAATTCTTCT TTCTC M CG CTGCAGAGTG TAGATCCCAA AAATTACCCA AAGAAGAAGA TGGAAAAGCG A'LTTGTCTTC AACAAGATAG AAATCAATAA CAAGCTGGAA TI1TGAGTCTG CCCAGYTCCC CAACTGGTAC ATCAGCACCT CTCAAGCAGA AAACATGCCC GTCTTCCTGG GAGGGACCAA AGGCGGCCAG 30 GATATAACTG ACTTCACCAT GCAA'ITGTG TCTrCCTAAA GAGAGCTGTA CCCAGAGAGT CCTGTGCTGA ATGTGGACTC AATCCCTAGG GCTGGCAGAA AGGGAACAGA AAGGTI=G AGTACGGCTA TAGCCTGGAC 'ITTCCTGTTG TCTACACCAA TGCCCAACTG CCTGCCTTAG GGTAGTGCTA AGAGGATCTC CTGTCCATCA GCCAGGACAG TCAGCTCTCT CCYI'TCAGGG CCAATCCCCA GCCC'IIGT TGAGCCAGGC CTCTCTCACC TCTCCTACTC ACYI7AAAGCC CGCCTGACAG AAACCACGGC CACKITTGGT TCTAAGAAAC CCTCTGTCAT 35 TCGCTCCCAC ATTCTGATGA GCAACCGCTJ' CCCTATTTAT TTATATTT GTITGTITGT rrTGAJTCAT TGGTCTAA FI TAYI7CAAAGG GGGCAAGAAG TAGCAGTGTC TGTAAAAGAG CCTAG~fT= AATAGCTATG GAATCAATTC AATTTGGACT GGTGTGCTCT CTAAATCA AGTCC'TrAA 'TAAGACTGA AAATATATAA GCTCAGATTA 'ITTAAATGGG AATATrATA AATGAGCAAA TATCATACTG TTCAATGGTT CTGAAATAAA CTTCACTGAA GAAAAAAAAA AAAGGGTCTC TCCTGATCAT TGACTGTCTG GATTGACACT GACAGTAAGC 40 AAACAGGCTG TGAGAGTTCT TGGGACTAAG CCCACTCCTC ATTGCTGAGT GCTGCAAGTA CCTAGAAATA TCCTTGGCCA CCGAAGACTA TCCTCCTCAC CCATCCCCTT TATPrCGTTG TTCAACAGAA GGATAYI'CAG TGCACATCTG GAACAGGATC AGCTGAAGCA CTGCAGGGAG TCAGGACTGG TAGTAACAGC TACCATGATT TATCTATCAA TGCACCAAAC ATCTGTTGAG CAAGCGCTAT GTACTAGGAG CTGGGAGTAC AGAGATGAGA ACAGTCACAA GTCCCTCCTC AGATAGGAGA GGCAGCTAGT TATAAGCAGA ACAAGGTAAC ATGACAAGTA 45 GAGTAAGATA GAAGAACGAA GAGGAGTAGC CAGGAAGGAG GGAGGAGAAC GACATAAGAA TCAAGCCTAA AGGGATAAAC AGAAGAT11TC CACACATGGG CTGGGCCAAT TGGGTGTCGG TrFACGCCTGT AATCCCAGCA CTTTGGGTGG CAGGGGCAGA AAGATCGCTT1 GAGCCCAGGA GTTCAAGACC AGCCTGGGCA ACATAGTGAG ACTCCCATCT CTACAAAAAA TAAATAAATA AATAAAACAA TCAGCCAGGC ATGCTGGCAT GCACCTGTAG TCCTAGCTAC 'ITGGGAAGCT GACACTGGAG GATTGCTTGA GCCCAGAAGT TCAAGACTGC AGTGAGCTTA 50 TCCGTTGACC TGCAGGTCGA C ACAAACCT= TCGAGGCAAA AGGCAAAAAA GGCTGCTCTG GGATI7CTCTT CAGCCAATCT TCAATGCTCA AGTGTCTGAA GCAGCCATGG CAGAAGTACC TAAGCTCGCC AGTGAAATGA TGGCTTATTA CAGTGGCAAT GAGGATGACT TGTIT=GA AGCTGATGGC CCTAAACAGA TGAAGTGCTC CTTCCAGGAC CTGGACCTCT GCCCTCTGGA TGGCGGCATC CAGCTACGAA TCTCCGACCA CCACTACAGC AAGGGC'1CA GGCAGGCCGC GTCAGTTGTT GTGGCCATGG ACAAGCTGAG GAAGATGCTG GTTCCCTGCC 55 CACAGACCTT1 CCAGGAGAAT GACCTGAGCA CCTTC ITTCC CTTCATCTTT GAAGAAGAAC CTATCTTCTT CGACACATGG GATAACGAGG CTTATGTGCA CGATGCACCT GTACGATCAC TGAACTGCAC GCTCCGGGAC TCACAGCAAA AAAGC'ITGGT GATGTCTGGT CCATATGAAC TGAAAGCTCT CCACCTCCAG GGACAGGATA TGGAGCAACA AGTGGTGTTC TCCATGTCCT TTGTACAAGG AGAAGAAAGT AATGACAAAA TACCTGTGGC CTTGGGCCTC AAGGAAAAGA ATCTGTACCT GTCCTGCGTG TT1GAAAGATG ATAAGCCCAC TCTACAGCTG 60 GAGAGTGTAG ATCCCAAAAA TI1ACCCAAAG AAGAAGATGG AAAAGCGA Fr TGTCTTCAAC AAGATAGAAA TCAATAACAA GCTGGAATTT GAGTCTGCCC AGTTCCCCAA CTGGTACATC AGCACCTCTC AAGCAGAAAA CATGCCCGTC TTCCTGGGAG GGACCAAAGG CGGCCAGGAT ATAACTGACT TCACCATGCA ATrGTGTCT TCCTAAAGAG AGCTGTACCC AGAGAGTCCT GTGCTGAATG TGGACTCAAT CCCTAGGGCT GGCAGAAAGG GAACAGAAAG GTL1TGAGT ACGGCTATAG CCTGGACTI1 CCTGTTGTCT ACACCAATGC CCAACTGCCT 65 GCCTTAGGGT AGTGCTAAGA GGATCTCCTG TCCATCAGCC AGGACAGTCA GCTCTCTCCT ITCAGGGCCA ATCCCAGCCC =mGTrGAG CCAGGCCTCT CTCACCTCTC CTACTCACTT AAAGCCCGCC TGACAGAAAC WO 00/62736 PCT/USOO/08020 98 CAGGCCACAT 'FrrGGTTCTA AGAAACCCTC CTCTGTCAT7 CGCTCCCACA TTCTGATGAG CAACCGC'ITC CCTA ITTAIT TA'TrA1TIG TTrGTrGTT TTGATTCAIT GGTCTAAMT KUTCAAAGGG GGCAAGAAGT AGCAGTGTCT GTAAAAGAGC CTAGThTrA ATAGCTATGG AATCAATTCA A'TrTGGACTG GTGTGCTCTC TTAAATCAA GTCCTI17AAT TAAGACTGAA AATATATAAG CTCAGATTAT TTAAATGGGA ATATTTATAA 5 ATGAGCAAAT ATCATACTGT TCAATGGTTC TCAAATAAAC ITrCACT CTGGCAGGAG TAGCAGCTGC CCCTTGGCGC GACTGCTGGA GCCGCGAACT AGAGAAACAC AGACACGCCT CATAGAGCAA CGGCGTCTCT CGGAGCGTGG AGCCCGCCAA GCTCGAGCTG AGCTI17CGCT TGCCGTCCAC CACTGCCCAC ACTGTCG~T GCTGCCATCG CAGACCTGCT GCTGACTTCC ATCCCTCTGG ATCCGGCAAG GGCCTGCGAT 'ITGACAATG TCAAGA'ITTA CCGTATATCC CTG'ITTGTTT GGATACACCA GTGACGTCCA CTTCTAGAAG ACAAAG~rrAT 10 ATTACTTAAA CAACCAAAGA TATGAAACTA TCCATGAAGA ACAATATTrAT CAATACACAG CAGTCTThTG TAACCATGCC CAATGTGATT GTACCAGATA TI'GAAAAGGA AATACGAAGG ATGGAAAATG GAGCATGCAG CTCCTITTCT GAGGATGATG ACAGTGCCTC TACATCTGAA GAATCAGAGA ATGAAAACCC TCATGCAAGG GGTVICCTTTA GTTATAAGTC ACTCAGAAAG GGAGGA:CCAT CACAGAGGGA GCAGTACCTG CCTGGTGCCA 'ITGCCATTT' TAATGTGAAC AACAGCGACA ATAAGGACCA GGAACCAGAA GAAAAAAAGA AAAAGAAAAA 15 AGAAAAGAAG AGCAAGTCAG ATGATAAAAA CGAAAATAAA AACGACCCAA AGAAGAAGAT GGAAAAGCGA ATGGCCAAAG TI1CCAGACAT GM1]GAAGAC CTGAAGAACT GTTACAGTGA AAATGAAGAA GACAGTTCCT CCNL17GATCA TCTGTCTCTG AATCAGAAAT CCTTCTATCA TGTAAGCTAT GGCCCACTCC ATGAAGGCTG CATGGATCAA TCTGTGTCTC TGAGTATCTC TGAAACCTCT AAAACATCCA AGCTrACCTT CAAGGAGAGC ATGGTGGTAG TAGCAACCAA CGGGAAGGTT CTGAAGAAGA GACGGTI'GAG TI'AAGCCAA TCCATCACTG 20 ATGATGACCT GGAGGCCATC GCCAATGACT CAGAGGAAGA AATCATCAAG CCTAGGTCAG CACCYTT-AG CTTCCTGAGC AATGTGAAAT ACAACT]7TAT GAGGATCATC AAATACGAAT TCATCCTGAA TGACGCCCTC AATCAAAGTA TAATrCGAGC CAATGATCAG TACCTCACGG CTGCTGCA'IT ACATAATCTG GATGAAGCAG TGAANITTTGA CATGGGTGCT TATAAGTCAT CAAAGGATGA TGCTAAAATT ACCGTGATTC TAAGAATCTC AAAAACTCAA TTGTATGTGA CTGCCCAAGA TGAAGACCAA CCAGTGCTGC TGAAGGAGAT GCCTGAGATA 25 CCCAAAACCA TCACAGGTAG TGAGACCAAC CTCCTCTTCT TCTGGGAAAC TCACGGCACT AAGAACTATT TCACATCAGT TGCCCATCCA AACTrG'TrTA TFGCCACAAA GCAAGACTAC TGGGTGTGCT TGGCAGGGGG GCCACCCTCT ATCACTGACT TTCAGATACT GGAAAACCAG GCGTAGGTCT GGAGTCTCAC TTGTCTCACT TGTGCAGTGT TGACAGT17CA TATGTACCAT GTACATGAAG AAGCTAAATC C'TrACTGTT AGTCATITGC TGAGCATGTA CTGAGCCTI1G TAATTCTAAA TGAATGTA CACTCTITGT AAGAGTGGAA. CCAACACTAA 30 CATATAATGT TGTTAT117AA AGAACACCCT ATATITGCA TAGTACCAAT CATTrTAA'rr A'FrATTC'rrC ATAACAATTT TAGGAGGACC AGAGCTACTG ACTATGGCTA CCAAAAAGAC TCTACCCATA TTACAGATGG GCAAATTAAG GCATAAGAAA ACTAAGAAAT ATGCACAATA GCAGTTGAAA CAAGAAGCCA CAGACCTAGG ATJTCATGAT 'FrCAT'FrCAA CTGTI17GCCT TCTGCITVFA AGTTGCTGAT GAACTCTTAA TCAAATAGCA TAAGTTL1CTG GGACCTCAGT T'FrATCATTT TCAAAATGGA GGGAATAATA CCTAAGCCTTr CCTGCCGCAA 35 CAGTTITA TGCTAATCAG GGAGGTCATT TTGGTAAAAT ACTTCTCGAA GCCGAGCCTC AAGATGAAGG CAAAGCACGA AATGTTAT TTTAA F7ATT A1TIATATAT GTATTTATAA ATATA ITTAA GATAATTATA ATATACTATA TTFATGGGAA CCCCTTCATC CTCTGAGTGT GACCAGGCAT CCTCCACAAT AGCAGACAGT G TTCTGGG ATAAGTAAGT TTGATTTCAT TAATACAGGG CA=VGGTC CAAGTrGTGC 'I1ATCCCATA GCCAGGAAAC TCTGCATT1CT AGTAC'ITGGG AGACCTGTAA TCATATAATA AATGTACAY7 AATrACC'ITG 40 AGCCAGTAAT TGGTCCGATC TITGACTCTT TTrGCCATTAA ACTTACCTGG GCATTCCTrGT FrCATTCAAT TCCACCTGCA ATCAAGTCCT ACAAGCTAAA ATTAGATGAA CTCAACTTTG ACAACCATAG ACCACTGTrrA TCAAAACTr CTITCTGGA ATGTAATCAA TG'rrrCFCT AGGTTCTAAA AATTGTGATC AGACCATAAT G'FrACATrAT TATCAACAAT AGTGATTGAT AGAGTG'ITAT CAGTCATAAC TAAATAAAGC 'I1?GCAAGTGA GGGAGTCATT TCATTGGCGT TTGAGTCAGC AAAGAAGTCA AG AGCTGCCAGC CAGAGAGGGA 45 GTCATTTCAT TGGCGTTTGA GTCAGCAAAG AAGTCAAGAT GGCCAAAGTT CCAGACATGT TTGAAGACCT GAAGAACTGT TACAGTGAAA ATGAAGAAGA CAGTTCCTCC ATrGATCATC TGTCTCTGAA TCAGAAATCC TTCTATCATG TAAGCTATGG CCCACTCCAT GAAGGCTGCA TGGATCAATC TGTGTCTCTG AGTATCTCTG AAACCTCTAA AACATCCAAG CTTAC = CA AGGAGAGGAT GGTGGTAGTA GCAACCAACG GGAAGGTTCT GAAGAAGAGA CGGTTGAGTT1 TAAGCCAATC CATCACTGAT GATGACCTGG AGGCCATCGC CAATGACTCA 50 GAGGAAGAAA TCATCAAGCC TAGGTCATCA CC=rAGCT TCCTGAGCAA TGTGAAATAC AACT'JTATGA GGATCATCAA ATACGAATTC ATCCTGAATG ACGCCCTrCAA TCAAAGTATA ATrCGAGCCA ATGATCAGTA CCTCACGGCT GCTGCATTAC ATAATCTGGA TGAAGCAGTG AAATTTGACA TGGGTGCTTA TAAGTCATCA AAGGATGATG CTAAAATTAC CGTGATTCTA AGAATCTCAA AAACTCAAYF GTATGTGACT GCCCAAGATG AAGACCAACC AGTGCTGCTG AAGGAGATGC CTGAGATACC CAAAACCATC ACAGGTAGTG AGACCAACCT 55 CCTCTTCTTC TGGGAAACTC ACGGCACTAA GAACTATI17C ACATCAGTrG CCCATCCAAA CTTGTTTATT GCCACAAAGC AAGACTACTG GGTGTGCTTG GCAGGGGGGC CACCCTCTAT CACTGAC'TrT CAGATACTGG AAAACCAGGC GTAGGTCTGG AGTCTCACT11 GTCTCA=1G TGCAGTG'ITG ACAGTTCATA TGTACCATGT ACATGAAGAA GCTAAATCCT 3TACTG'ITAG TCATT7GCTG AGCATGTACT GAGCCTTGTA ATTrCTAAATG AATGTTTACA CTCTI17GTAA GAGTGGAACC AACACTAACA TATAATG'rrG TTATTTAAAG AACACCCTAT 60 AT1TGCATA GTACCAATCA =P1AAT]7AT TATTCTTCAT AACAATITA GGAGGACCAG AGCTACTGAC TATGGCTACC AAAAAGACTC TACCCATATT ACAGATGGGC AAATTAA.GGC ATAAGAAAAC TAAGAAATAT GCACAATAGC AGTCGAAACA AGAAGCCACA GACCTAGGAT TTCATGA'rrr CATTTCAACT GTTTfGCCTTC TGCThL1?AAG TTGCTGATGA ACTCTTAATC AAATAGCATA AGMTCTGGG ACCTCAGTrT TATCA ITTC AAAATGGAGG GAATAATACC TAAGCCTTCC TGCCGCAACA GTIT11ATG CTAATCAGGG AGGTCAYTT~ 65 GGTAAAATAC TT1CTCGAAGC CGAGCCTCAA GATGAAGGCA AAGCACGAAA. TGTTATTTTT TAATTATTAT TrATATATGT ATTTATAAAT ATAITI'AAGA TAATTATAAT ATACTATAYT TATGGGAACC CCTTCATCCT WO 00/62736 PCT/US00/08020 99 CTGAGTGTGA CCAGGCATCC TCCACAATAG CAGACAGTGT TCTGGGAT AAGTAAGTTT GATTTCATTA ATACAGGGCA TTTTGGTCCA AGTTGTGCTT ATCCCATAGC CAGGAAACTC TGCATTCTAG TACTTGGGAG ACCTGTAATC ATATAATAAA TGTACATTAA TTACCTTGAG CCAGTAATTG GTCCGATCTT TGACTCTT GCCATTAAAC TTACCTGGGC ATTCTTGTTT CATTCAATTC CACCTGCAAT CAAGTCCTAC AAGCTAAAAT 5 TAGATGAACT CAACTTTGAC AACCATGAGA CCACTGTTAT CAAAACTTTC TTTTCTGGAA TGTAATCAAT GTTTCTTCTA GGTTCTAAAA ATTGTGATCA GACCATAATG TTACATTATT ATCAACAATA GTGATTGATA GAGTGTTATC AGTCATAACT AAATAAAGCT TGCAACAAAA TTCTCTG GCTCAGGGCA CATGCCTCCC CTCCCCAGGC CGCGGCCCAG CTGACCCTCG GGGCTCCCCC GGCAGCGGAC AGGGAAGGGT TAAAGGCCCC CGGCTCCCTG CCCCCTGCCC TGGGGAACCC CTGGCCCTGT GGGGACATGA ACTGTGTTTG CCGCCTGGTC 10 CTGGTCGTGC TGAGCCTGTG GCCAGATACA GCTGTCGCCC CTGGGCCACC ACCTGGCCCC CCTCGAGTTT CCCCAGACCC TCGGGCCGAG CTGGACAGCA CCGTGCTCCT GACCCGCTCT CTCCTGGCGG ACACGCGGCA GCTGGCTGCA CAGCTGAGGG ACAAATTCCC AGCTGACGGG GACCACAACC TGGATTCCCT GCCCACCCTG GCCATGAGTG CGGGGGCACT GGGAGCTCTA CAGCTCCCAG GTGTGCTGAC AAGGCTGCGA GCGGACCTAC TGTCCTACCT GCGGCACGTG CAGTGGCTGC GCCGGGCAGG TGGCTCTTCC CTGAAGACCC TGGAGCCCGA 15 GCTGGGCACC CTGCAGGCCC GACTGGACCG GCTGCTGCGC CGGCTGCAGC TCCTGATGTC CCGCCTGGCC CTGCCCCAGC CACCCCCGGA CCCGCCGGCG CCCCCGCTGG CGCCCCCCTC CTCAGCCTGG GGGGGCATCA GGGCCGCCCA CGCCATCCTG GGGGGGCTGC ACCTGACACT TGACTGGGCC GTGAGGGGAC TGCTGCTGCT GAAGACTCGG CTGTGACCCG GGGCCCAAAG CCACCACCGT CCTTCCAAAG CCAGATCTTA TATTTATT TATTTCAGTA CTGGGGGCGA AACAGCCAGG TGATCCCCCC GCCATTATCT CCCCCTAGTT AGAGACAGTC 20 CTTCCGTGAG GCCTGGGGGA CATCTGTGCC TTATTTATAC TTATTTATTT CAGGAGCAGG GGTGGGAGGC AGGTGGACTC CTGGGTCCCC GAGGAGGAGG GGACTGGGGT CCCGGATTCT TGGGTCTCCA AGAAGTCTGT CCACAGACTT CTGCCCTGGC TCTTCCCCAT CTAGGCCTGG GCAGGAACAT ATATTATTTA TTTAAGCAAT TACTTTCAT GTTGGGGTGG GGACGGAGGG GAAAGGGAAG CCTGGGTTTT TGTACAAAAA TGTGAGAAAC CTTTGTGAGA CAGAGAACAG GGAATTAAAT GTGTCATACA TATCC CAGCTGCGGC ATCCTCTGTC 25 TCAGAGTCTT GGTGTCTCTG TTCCTTTCCC CTCGGGGTCT CCCTGGGTCT CCCCAAGTCC CTCCTGCTGT CTTCCTCCCG CTCTCTGATC TCTGACTCCC AGAACCTCTC CCTCTGTCTC CAGGGCTGCC CCTCTGATCC TCTTTGCTTC TCTGGTGTGT CTCTCTGGCT GCCTCCATCT CTGTGGATCT CCGTCTCCCT GTCTCTGTCT CAGTCTGTCC TTCACTCTGT GTGTGTGTGT GTCTCTCTCT CTCTCTCTCC TTCCCTTCCA CTCCCTCTTC CTCCTGCCTC CACCTCTCCA GGCCCCTGTC TTGTCCCTCC GTCCGGCCTT TCTCTGCCTT TCCGTCCTCC 30 TGCCTCCCCA TCTCTCTCTG CTAGTCCTGT CCAGCCGGAC CCCCACCCAC AGTCGGGCCC CAGCGCTTGA GCCTGAGTGT CTGCTCCGGC CCGTGGAGGT GGAGGGAGGG GACGCCAATG ACCTCACCAG CCCCTCTCCG ACCACCCCCC CCTTTCCCTT TTCAACTT CCAACTTTC CTTCCGTGCC CTCCTCCGAG CGCGGCGGCG TGAGCCCTGC AAGGCAGCCG CTCCGTCTGA ATGGAAAAGG CAGGCAGGGA GGGTGAGTCA GGATGTGTCA GGCCGGCCCT CCCCTGCCGC CTGCCCCCCG CCCGCCCGCC CCAGGCCCCC TATATAACCC CCCAGGCGTC 35 CACACTCCCT CACTGCCGCG GGCCCTGCTG CTCAGGGCAC ATGCCTCCCC TCCCCAGCCG CGGGCCCAGC TGACCCTCGG GGCTCCCCCG GCAGCGGACA GGGAAGGGTT AAAGGCCCCC GGCTCCCTGC CCCCTGCCCT GGGGAACCCC TGGCCCTGTG GGGACATGAA CTGTAAGTTG GTTCATGGGG AGGGTGGAGG GGACAGGGAG GCAGGGAGGA GAGGGACCCA CGGCGGGGGT GGGAGCAGAC CCCGCTGAGT CGCACAGAGA GGGACCCGGA GACAGGCAGC CGGGGAGGAG AGCAGCTTCG GAGACAGGAG GCGGCGGAGG AGATGGGCAG AGAGAGACAC 40 AGACAGGAGC GGATGGAGGC AGCCAATCAG AGGCGCCGCA GGAGGGACGG GCCAGACAGG GCCCGAGAGG AGCGAGACGC GAGACCGAGC AGGGGCAGGG ACGCAGGGAC TGGTGCCGGG AGGGAGGTGA CCCCCATCGA CCCAGGCCCC AGGGAGCCCG CGGGGACCGG GAGACTCCCT GGGATTCCGG CAGAGAGGCT CCGGAGGGAA ACTGAGGCAG GGTCCGCGGA GAGCGGAGCA AGCCAGGGAG TAGCGACCCC AGCCGGGGGG AGGAGAGAGA CTGGGCGCCG GGGGAAAGCG GGGAGAGCCG GGCAGATGCG GCCGACGGAG GCGCGGACAG ACCGACGGCT 45 GGCGGGCCCG GGGGGCGGGC TGGGGGTGTG CGAGGCGCGG GCGGCCGGGG AGCGCTGATT GGCTGGCGGG TGGCCGGGTG GGCGGGGCGG CCGGGGTGGG CTGCGGGGAG CGAGCTCCGG ACCCCCGCGC CCCCGGCGCC CCCCGCGCCC CCCGCCGCCA GCTCTCCCGC TCCCGGCGCC CGGCCGGGCC ATGGCTCTGC CCCTCTCCGC CCAGGTGCGC TGCGGCCCGG GCTTCTGCCG CCCACCCGGC GGGCTCCTGG GAGGGCGTCT AAGGGGTCTC CCGTGGGAGA GGTCCGTGTC TCCCGGACTC CGTCCTGGGC TITTGGCTCC TTCCCCTGCT CCCAGCCAGC 50 TCGGGCTCCC GCGGCCCGGG GAGGGGGCAG GTTCTGGCCT GTGCCTCCCC CACCATCCGC GCCCCGGGGC CCAGATTCCG GCGTCCGGGG GCGGACGGGA GACGCCCGGG CCGCGTCTGC TCCGACGGGC GGGGCAGCCA GAGCCAGGGA GGGAGAGGGA AGCCCGCCTG GCCCTGCGAC CTGCCCGCGG GCGTTCCACC CTGGGACTTA AGACCTCCAG CTCCATCCTC CCTAAGGCCG GGAGTCCAGG CCCCAGACCC TCCTCCCCGA GACCCAGGAG TCCAGACCCC AGGCCTTCCT CCCTCAGACC TAGGAGTCCA GGCCCCCAGC CTCTCCTCCC TCAGACCCAG 55 GAGGAGTCCA GACCCCAGTT CCTCCTCCCT CAGACCCGGG AGTCCAGCCC AGGCCCTCCT CTCTCAGACC CGGAGTCCAG CCTGAGCTCT CTGCCTTATC CTGCCCCCAG GTGTTTGCCG CCTGGTCCTG GTCGTGCTGA GCCTGTGGCC AGATACAGCT GTCGCCCCTG GGCCACCACC TGGCCCCCCT CGAGTTTCCC CAGACCCTCG GGCCGAGCTG GACAGCACCG TGCTCCTGAC CCGCTCTCTC CTGGCGGACA CGCGGCAGCT GGCTGCACAG CTGGTAGGAG AGACTGGGCT GGGGCCAGCA CAGGAGTGAG AGGCAGAGAG GAACGGAGAG GAGTCTGCGG 60 GCAGCCACTT GGAGGGGTTC TGGGCTCTCA GGTGGCAGAG TGAGGGAGGG GAAGAGTTGG GGGCCTGGCG TGGGGGATGG AGGGAGCCCC GAGGCTGGGC AGGGGCCACC TCACAGC TT TTTCCCTGCC AGAGGGACAA ATTCCCAGCT GACGGGGACC ACAACCTGGA TTCCCTGCCC ACCCTGGCCA TGAGTGCAGG GGCACTGGGA GCTCTACAGG TAAGGGCAAG GGAGTGGGCT GGGGACAAGG TGGGAGGCAG GCAGTGAAGG GGGCGGGGAG GATGAGGGGC ACTGGTCGGG TGTTCTCTGA TGTCCCGGCT CTATCCCCAG CTCCCAGGTG TGCTGACAAG 65 GCTGCGAGCG GACCTACTGT CCTACCTGCG GCACGTGCAG TGGCTGCGCC GGGCAGGTGG CTCTTCCCTG AAGACCCTGG AGCCCGAGCT GGGCACCCTG CAGGCCCGAC TGGACCGGCT GCTGCGCCGG CTGCAGCTCC WO 00/62736 PCT/USOO/08020 100 TGGTATGTCC TGGCCCCAAG ACCTGACACC CCAGACCCCC ACCCCTGGCC CCAAAATCCT GTGGCCTGAG TCCTTGAAGC CTGAGACCCC AGACCCGAGT GCAACAGCCC CGCTCTGAGA CCCTGACACC CTAACAGCCC GCTCTGAGAC CCTGACACCG TAACAGCCCC GCTCTGAGAC CCTGACCCTA ACAGTCCTGC TCTGAGACCC TGACCCTGCA GTCCCAAGAT CCTGTGGCCC TGAGACCCTG AGGCCCTAGA CCCCCAAATC CTGCCCAGAA 5 ACTTCAAATT CTCACCCAAG ACCCTGAGAC TCCATCATCC ATGACCTCAA AGTCCCCAGA TCCCAGCCCC TAAGACCCAA GACCCCATCC TGAAGCCCAA AGCCTTGAGA ATTCAAATCC TCACCTCAAG ACTTGGAGAC CCTGGCCCCA TGACATTGAA AACCATGGAC CTGGCCAGGC GTGGTGGCTC ACGCCTGTAA TCCCAGCACT TTGGGAGGCC GAGGCAAGTG GATCACCTGA GGTCGGGAGT TCAAGACCAG CCAGACCAAC ATGGTGAAAC CCTGTCTCTA CTAAAAATAC AAAATrAGCC AGGCGTGGTG GTGCATGCCT GTAATCCCAG CTACTTGGGA 10 GGCTGAGGCA GGAGAATCGC TTGAACCTGG GAGGCGGAGG TTGCAGTGAG CCGAGATCGC ACCATTACAC TCCAGCCTGG GCAACAAGAG CAAAACTCCC TCTCTCTCAA AAAAAAAAAA AAAAAAAAAA AAGAAGGAAA AGAAAACCAT GGACCTCCAG ACCCTGAGAC CCCAGGCCCC AGCCCTGAGA TCCTGACATC TTAAAGATCC CAGGCCCTAA GATACAAGAC CTTGACCCAA AGCCAGCCTT GGGACCCTGG CTGTACAAAC CCAAGACCTC CAGGACCTAG ACCCCGAGCC CTGAGGCCCT ATGTCTCACT CCCAACATCG AAAACCCTGA CACCTCAGAT 15 CCTGAGCCTG CGCCTGTACG ACTCCAAGAC CCTCACTTCC AAAGCCAGGC CCAAAGCCCT GAGACCAGAA GACTTCAAAC CCTGGTTCTT GGGCCTAACT CCAAAGACCC TGGATCTCAA ATTCCAACTT CTAGCTCTGA GACTCCAGCC CTCACCCATG AGTTCCTGAA CTTGAACCCA GAGACCCCAT CTCTAAGACT TCAGCCTTGA GATCCAGGGC CTGACCCTAG ACTCGAGCCC ACAGACCTCA GATACTGTCT GTAAAACCCC AGCTCTGGTG GGGAGCAGTG GCTCACTCCT GTAATCCCAA GGCAGGGGAG GCCAAGGCAG AAGGACCTCT TGAGGCCATG 20 AGTTTGAGAC AGCCTGGGCA GCATAGCAAG ACTCTGTTTC TTAATTATTA TTATTATTAT TATTT7GG AGACAGAGTC TCGCGCTCTG TTGCCCAGGC TAGAGTGCAA TGGTGCCATT TCGGCTTGCT GGAACCTCCG CCTCCTGGGC TCAAGCGATT CTCCTGCCTC AGCCTCCTGA GTAGCTGGGA CTTCAGGTGC ACACTGCCAC ACCCGGATAA TTTTTTTGTA TTAGTAGA CACAGGGTTT CACCGTGTTG CCCAGGCTGG TCACAAACTC CTGAGCTCAG GCCATCCGCC CGCCTCGGCC TCCCAAAGCG CTGGGATAAC AGGCGTGACG CCGCGCCTGG 25 CTTCTTAATT GTTCTAACAG CAGCGACAAC AACAAAAACC CAGCTCTGAG ATTCCAGCCC CGGCGACTCT AACAGTCCCA GGCCCGATCC CTCACCTAGA ACCGAGATGC CAGCCCTGAC TCCACAGACT TCACCCCCAA CCCCCACACT CAGCTCTGGA AGCCCGTCCT GACTCCAGCC TCCATITTCG GAACCCCACA GCCTGAAGAG CTCCCGGCCT AAACACTTCA CCCCACGCGC CACAGTCCCC CTGTGAATAT GCAGCCCCGA TTCAGCTGCA GCTCCACAGC ACCCCTGCCC TGCACCCCCG CTGCACCCCC TACCTGTGAC TCACCTCTCT CCTCTCCCCA 30 CAGATGTCCC GCCTGGCCCT GCCCCAGCCA CCCCCGGACC CGCCGGCGCC CCCGCTGGCG CCCCCCTCCT CAGCCTGGGG GGGCATCAGG GCCGCCCACG CCATCCTGGG GGGGCTGCAC CTGACACTTG ACTGGGCCGT GAGGGGACTG CTGCTGCTGA AGACTCGGCT GTGACCCGGG GCCCAAAGCC ACCACCGTCC TTCCAAAGCC AGATCTTATT TATTTATTTA TCAGTACT GGGGGCGAAA CAGCCAGGTG ATCCCCCCGC CATTATCTCC CCCTAGTTAG AGACAGTCCT TCCGTGAGGC CTGGGGGGCA TCTGTGCCTT ATTTATACTT ATTTATTTCA 35 GGAGCAGGGG TGGGAGGCAG GTGGACTCCT GGGTCCCCGA GGAGGAGGGG ACTGGGGTCC CGGATTCTTG GGTCTCCAAG AAGTCTGTCC ACAGACTTCT GCCCTGGCTC TTCCCCATCT AGGCCTGGGC AGGAACATAT ATTATTTATT TAAGCAATTA CTTTTCATGT TGGGGTGGGG ACGGAGGGGA AAGGGAAGCC TGGGTTTG TACAAAAATG TGAGAAACCT TTGTGAGACA GAGAACAGGG AATTAAATGT GTCATACATA TCCACTTGAG GGCGATTTGT CTGAGAGCTG GGGCTGGATG CTTGGGTAAC TGGGGCAGGG CAGGTGGAGG GGAGACCTCC 40 ATTCAGGTGG AGGTCCCGAG TGGGCGGGGC AGCGACTGGG AGATGGGTCG GTCACCCAGA CAGCTCTGTG GAGGCAGGGT CTGAGCCTTG CCTGGGGCCC CGCACTGCAT AGGGCCGTT GTTTGTTTT TGAGATGGAG TCTCGCTCTG TTGCCTAGGC TGGAGTGCAG TGAGGCAATC TAAGGTCACT GCAACCTCCA CCTCCCGGGT TCAAGCAATT CTCCTGCCTC AGCCTCCCGA TTAGCTGGGA TCACAGGTGT GCACCACCAT GCCCAGCTAA TTATTTATTT CTTTGTATT TTTAGTAGAG ACAGGGTTTC ACCATGTTGG CCAGGCTGGT TTCGAACTCC 45 TGACCTCAGG TGATCCTCCT GCCTCGGCCT CCCAAAGTGC TGGGATTACA GGTGTGAGCC ACCACACCTG ACCCATAGGT CTTCAATAAA TATTTAATGG AAGGTTCCAC AAGTCACCCT GTGATCAACA GTACCCGTAT GGGACAAAGC TGCAAGGTCA AGATGGTTCA TTATGGCTGT GTTCACCATA GCAAACTGGA AACAATCTAG ATATCCAACA GTGAGGGTTA AGCAACATGG TGCATCTGTG GATAGAACGC CACCCAGCCG CCCGGAGCAG GGACTGTCAT TCAGGGAGGC TAAGGAGAGA GGCTTGCTTG GGATATAGAA AGATATCCTG ACATTGGCCA 50 GGCATGGTGG CTCACGCCTG TAATCCTGGC ACTTrGGGAG GACGAAGCGA GTGGATCACT GAAGTCCAAG AGTTTGAGAC CGGCCTGCGA GACATGGCAA AACCCTGTCT CAAAAAAGAA AGAATGATGT CCTGACATGA AACAGCAGGC TACAAAACCA CTGCATGCTG TGATCCCAAT TTTGTGTT TCTTTCTATA TATGGATTAA AACAAAAATC CTAAAGGGAA ATACGCCAAA ATGTTGACAA TGACTGTCTC CAGGTCAAAG GAGAGAGGTG GGATTGTGGG TGACTTTTAA TGTGTATGAT TGTCTGTATT TTACAGAATT TCTGCCATGA CTGTGTATTT 55 TGCATGACAC ATTTTAAAAA TAATAAACAC TATTTAGA ATAACAGAAT ATCAGCCTCC TCCTCTCCAA AAATAAGCCC TCAGGAGGGG ACAAAGTTGA CCGCTGATTG AGCCTGTCAG GGCTGTGCAC-3' (SEQ. ID NO:3004) Human Adenosine A, Receptor Nucleic Acid and Antisense Oligonucleotide Fragments 5'-ATGCCGCCCT CCATCTCAGC TTTCCAGGCC GCCTACATCG GCATCGAGGT GCTCATCGCC CTGGTCTCTG 60 TGCCCGGGAA CGTGCTGGTG ATCTGGGCGG TGAAGGTGAA CCAGGCGCTG CGGGATGCCA CCTTCTGCTT CATCGTCTCG CTGGCGGTGG CTGATGTGGC CGTGGGTGCC CTGGTCATCC CCCTCGCCAT CCTCATCAAC ATTGGGCCAC AGACCTACTT CCACACCTGC CTCATGGTTG CCTGTCCGGT CCTCATCCTC ACCCAGAGCT CCATCCTGGC CCTGCTGGCA ATTGCTGTGG ACCGCTACCT CCGGGTCAAG ATCCCTCTCC GGTACAAGAT GGTGGTGACC CCCCGGAGGG CGGCGGTGGC CATAGCCGGC TGCTGGATCC TCTCCTTCGT GGTGGGACTG 65 CCCCTATGT TTGGCTGGAA CAATCTGAGT GCGGTGGAGC GGGCCTGGGC AGCCAACGGC AGCATGGGGG WO 00/62736 PCT/USOO/08020 101 AGCCCGTGAT CAAGTGCGAG TTCGAGAAGG TCATCAGCAT GGAGTACATG GTCTACTTCA ACTTCTTTGT GTGGGTGCTG CCCCCGCTTC TCCTCATGGT CCTCATCTAC CTGGAGGTCT TCTACCTAAT CCGCAAGCAG CTCAACAAGA AGGTGTCGGC CTCCTCCGGC GACCCGCAGA AGTACTATGG GAAGGAGCTG AAGATCGCCA AGTCGCTGGC CCTCATCCTC TTCCTCTTTG CCCTCAGCTG GCTGCCTTTG CACATCCTCA ACTGCATCAC 5 CCTCTTCTGC CCGTCCTGCC ACAAGCCCAG CATCCTTACC TACATTGCCA TCTTCCTCAC GCACGGCAAC TCGGCCATGA ACCCCATTGT CTATGCCTrC CGCATCCAGA AGTTCCGCGT CACCTTCCTT AAGATTTGGA ATGACCATTT CCGCTGCCAG CCTGCACCTC CCATTGACGA GGATCTCCCA GAAGAGAGGC CTGATGACTA G ATGAGTGTCA GAAGTGTGAA GGGTGCCTGT TCTGAATCCC AGAGCCTCCT CTCCCTCTGT GAGGCTGGCA GGTGAGGAAG GGTTTAACCT CACTGGAAGG AATCCCTGGA GCTAGCGGCT GCTGAAGGCG TCGAGGTGTG 10 GGGGCACTTG GACAGAACAG TCAGGCAGCC GGGAGCTCTG CCAGCTTTGG TGACCTTGGG CCGGGCTGGG AGCGCTGCGG CGGGAGCCGG AGGACTATGA GCTGCCGCGC GTTGTCCAGA GCCCAGCCCA GCCCTACGCG CGCGGCCCGG AGCTCTGTTC CCTGGAACTT TGGGCACTGC CTCTGGGACC CCTGCCGGCC AGCAGGCAGG ATGGTGCTTG CCTCGTGCCC CTTGGTGCCC GTCTGCTGAT GTGCCCAGCC TGTGCCCGCC ATGCCGCCCT CCATCTCAGC TTTCCAGGCC GCCTACATCG GCATCGAGGT GCTCATCGCC CTGGTCTCTG TGCCCGGGAA 15 CGTGCTGGTG ATCTGGGCGG TGAAGGTGAA CCAGGCGCTG CGGGATGCCA CCTTCTGCTT CATCGTGTCG CTGGCGGTGG CTGATGTGGC CGTGGGTGCC CTGGTCATCC CCCTCGCCAT CCTCATCAAC ATTGGGCCAC AGACCTACTT CCACACCTGC CTCATGGTTG CCTGTCCGGT CCTCATCCTC ACCCAGAGCT CCATCCTGGC CCTGCTGGCA ATTGCTGTGG ACCGCTACCT CCGGGTCAAG ATCCCTCTCC GGTACAAGAT GGTGGTGACC CCCCGGAGGG CGGCGGTGGC CATAGCCGGC TGCTGGATCC TCTCCTTCGT GGTGGGACTG ACCCCTATGT 20 TTGGCTGGAA CAATCTGAGT GCGGTGGAGC GGGCCTGGGC AGCCAACGGC AGCATGGGGG AGCCCGTGAT CAAGTGCGAG TTCGAGAAGG TCATCAGCAT GGAGTACATG GTCTACTTCA ACTTCTTTGT GTGGGTGCTG CCCCCGCTTC TCCTCATGGT CCTCATCTAC CTGGAGGTCT TCTACCTAAT CCGCAAGCAG CTCAACAAGA AGGTGTCGGC CTCCTCCGGC GACCCGCAGA AGTACTATGG GAAGGAGCTG AAGATCGCCA AGTCGCTGGC CCTCATCCTC TTCCTCTTTG CCCTCAGCTG GCTGCCTTTG CACATCCTCA ACTGCATCAC CCTCTTCTGC 25 CCGTCCTGCC ACAAGCCCAG CATCCTTACC TACATTGCCA TCTTCCTCAC GCACGGCAAC TCGGCCATGA ACCCCATTGT CTATGCCTTC CGCATCCAGA AGTTCCGCGT CACCTTCCTT AAGATTTGGA ATGACCATTr CCGCTGCCAG CCTGCACCTC CCATTGACGA GGATCTCCCA GAAGAGAGGC CTGATGACTA GACCCCGCCT TCCGCTCCCA CCAGCCCACA TCCAGTGGGG TCTCAGTCCA GTCCTCACAT GCCCGCTGTC CCAGGGGTCT CCCTGAGCCT GCCCCAGCTG GGCTGTTGGC TGGGGGCATG GGGGAGGCTC TGAAGAGATA CCCACAGAGT 30 GTGGTCCCTC CACTAGGAGT TAACTACCCT ACACCTCTGG GCCCTGCAGG AGGCCTGGGA GGGCAAGGGT CCTACGGAGG GACCAGGTGT CTAGAGGCAA CAGTGTTCTG AGCCCCCACC TGCCTGACCA TCCCATGAGC AGTCCAGCGC TTCAGGGCTG GGCAGGTCCT GGGGAGGCTG AGACTGCAGA GGAGCCACCT GGGCTGGGAG AAGGTGCTTG GGCTTCTGCG GTGAGGCAGG GGAGTCTGCT TGTCTTAGAT GTTGGTGGTG CAGCCCCAGG ACCAAGCTTA AGGAGAGGAG AGCATCTGCT CTGAGACGGA TGGAAGGAGA GAGGTTGAGG ATGCACTGGC 35 CTGTTCTGTA GGAGAGACTG GCCAGAGGCA GCTAAGGGGC AGGAATCAAG GAGCCTCCGT TCCCACCTCT GAGGACTCTG GACCCCAGGC CATACCAGGT GCTAGGGTGC CTGCTCTCCT TGCCCTGGGC CAGCCCAGGA TTGTACGTGG GAGAGGCAGA AAGGGTAGGT TCAGTAATCA TTTCTGATGA TTTGCTGGAG TGCTGGCTCC ACGCCCTGGG GAGTGAGCTT GGTGCGGTAG GTGCTGGCCT CAAACAGCCA CGAGGTGGTA GCTCTGAGCC CTCCTTCTTG CCCTGAGCTT TCCGGGGAGG AGCCTGGAGT GTAATTACCT GTCATCTGGG CCACCAGCTC 40 CACTGGCCCC CGTTGCCGGG CCTGGACTGT CCTAGGTGAC CCCATCTCTG CTGCTTCTGG GCCTGATGGA GAGGAGAACA CTAGACATGC CAACTCGGGA GCATTCTGCC TGCCTGGGAA CGGGGTGGAC GAGGGAGTGT CTGTAAGGAC TCAGTGTTGA CTGTAGGCGC CCCTGGGGTG GGTTTAGCAG GCTGCAGCAG GCAGAGGAGG AGTACCCCCC TGAGAGCATG TGGGGGAAGG CCTTGCTGTC ATGTGAATCC CTCAATACCC CTAGTATCTG GCTGGGTTTT CAGGGGCTTT GGAAGCTCTG TTGCAGGTGT CCGGGGGTCT AGGACTTTAG GGATCTGGGA 45 TCTGGGGAAG GACCAACCCA TGCCCTGCCA AGCCTGGAGC CCCTGTGTTG GGGGGCAAGG TGGGGGAGCC TGGAGCCCCT GTGTGGGAGG GCGAGGCGGG GGAGCCTGGA GCCCCTGTGT GGGAGGGCGA GGCGGGGGAT CCTGGAGCCC CTGTGTCGGG GGGCGAGGGA GGGGAGGTGG CCGTCGGTTG ACCTTCTGAA CATGAGTGTC AACTCCAGGA CTTGCTTCCA AGCCCTTCCC TCTGTTGGAA ATTGGGTGTG CCCTGGCTCC CAAGGGAGGC CCATGTGACT AATAAAAAAC TGTGAACCCT CGCATTTGTG TTTTAATAAA AGAATCTGGA AGATAAATAG 50 TCTTGAAGAG AGACAAAGGA AGGAAAATTT AAATCCTTAG ATTCAAGCAG AAGAATTCCA TGTGGAAGGT TTGGGTTGTT GTTGTTGTTG TTTGGTGTGT TTTTTGTT TTTGTTT TGTTTTT TGAGATGGAG TCTCGCTGTG TTACCGGGAG CGACAGAGCC GCACGGCCGA GTCGAGTCCC AGCCAGCTAC CATCCCTCTG GAGCTTACCG GCCGGCCTTG GCTTCCCCAG GAATCCCTGG AGCTAGCGGC TGCTGAAGGC GTCGAGGTGT GGGGGCACTT GGACAGAACA GTCAGGCAGC CGGGAGCTCT GCCAGCTTTG GTGACCTTGG GTGCTTGCCT 55 CGTGCCCCTT GGTGCCCGTC TGCTGATGTG CCCAGCCTGT GCCCGCCATG CCGCCCTCCA TCTCAGCTTT CCAGGCCGCC TACATCGGCA TCGAGGTGCT CATCGCCCTG GTCTCTGTGC CCGGGAACGT GCTGGTGATC TGGGCGGTGA AGGTGAACCA GGCGCTGCGG GATGCCACCT TCTGCTTCAT CGTGTCGCTG GCGGTGGCTG ATGTGGCCGT GGGTGCCCTG GTCATCCCCC TCGCCATCCT CATCAACATT GGGCCACAGA CCTACTTCCA CACCTGCCTC ATGGTTGCCT GTCCGGTCCT CATCCTCACC CAGAGCTCCA TCCTGGCCCT GCTGGCAATT 60 GCTGTGGACC GCTACCTCCG GGTCAAGATC CCTCTCCGGT ACAAGATGGT GGTGACCCCC CGGAGGGCGG CGGTGGCCAT AGCCGGCTGC TGGATCCTCT CCTTCGTGGT GGGACTGACC CCTATGTT7G GCTGGAACAA TCTGAGTGCG GTGGAGCGGG CCTGGGCAGC CAACGGCAGC ATGGGGGAGC CCGTGATCAA GTGCGAGTTC GAGAAGGTCA TCAGCATGGA GTACATGGTC TACTTCAACT TCTTTGTGTG GGTGCTGCCC CCGCTTCTCC TCATGGTCCT CATCTACCTG GAGGTCTTCT ACCTAATCCG CAAGCAGCTC AACAAGAAGG TGTCGGCCTC 65 CTCCGGCGAC CCGCAGAAGT ACTATGGGAA GGAGCTGAAG ATCGCCAAGT CGCTGGCCCT CATCCTCTTC CTCTTTGCCC TCAGCTGGCT GCCTTGCAC ATCCTCAACT GCATCACCCT CTTCTGCCCG TCCTGCCACA WO 00/62736 PCT/USOO/08020 102 AGCCCAGCAT CCTTACCTAC ATTGCCATCT TCCTCACGCA CGGCAACTCG GCCATGAACC CCATTGTCTA TGCCTTCCGC ATCCAGAAGT TCCGCGTCAC CTTCCTTAAG ATTTGGAATG ACCATTTCCG CTGCCAGCCT GCACCTCCCA TTGACGAGGA TCTCCCAGAA GAGAGGCCTG ATGACTAGAC CCCGCCTTCC GCTCCCACCG CCCACATCCA GTGGGGTCTC AGTCCAGTCC TCACATGCCC GCTGTCCCAG GGGTCTCCCT GAGCCTGCCC 5 CAGCTGGGCT GTTGGCTGGG GGCATGGGGG AGGCTCTGAA GAGATACCCA CAGAGTGTGG TCCCTCCACT AGGAGTTAAC TACCCTACAC CTCTGGGCCC TGCAGGAGGC CTGGGAGGGC AAGGGTCCTA CGGAGGGACC AGGTGTCTAG AGGCAACAGT GTTCTGAGCC CCCACCTGCC TGACCATCCC ATGAGCAGTC CAGAGCTFCA GGGCTGGGCA GGTCCTGGGG AGGCTGAGAC TGCAGAGGAG CCACCTGGGC TGGGAGAAGG TGCTTGGGCT TCTGCGGTGA GGCAGGGGAG TCTGCTrGTC TTAGATGTTG GTGGTGCAGC CCCAGGACCA AGCTTAAGGA 10 GAGGAGAGCA TCTGCTCTGA GACGGATGGA AGGAGAGAGG TTGAGGATGC ACTGGCCTGT TCTGTAGGAG AGACTGGCCA GA GAT GGA GGG CGG CAT GGC GGG G CGG GTC GCC GG GGC GGG CBC BGG C GGC GGG CBC GC GGC CTG G GGB GGG CGG C GBT GGB GGG GG CTG GGC GC GGC CTG GAA AGC TGA GAT GGA GGG CGG CAT GGC GGG CAC AGG CTG GGC ATGCCGCCCT CCATCTCAGC TTTCCAGGCC GCCTACATCG GCATCGAGGT GCTCATCGCC CTGGTCTCTG TGCCCGGGAA CGTGCTGGTG ATCTGGGCGG 15 TGAAGGTGAA CCAGGCGCTG CGGGATGCCA CCTTCTGCTT CATCGTCTCG CTGGCGGTGG CTGATGTGGC CGTGGGTGCC CTGGTCATCC CCCTCGCCAT CCTCATCAAC ATTGGGCCAC AGACCTACTT CCACACCTGC CTCATGGTTG CCTGTCCGGT CCTCATCCTC ACCCAGAGCT CCATCCTGGC CCTGCTGGCA ATTGCTGTGG ACCGCTACCT CCGGGTCAAG ATCCCTCTCC GGTACAAGAT GGTGGTGACC CCCCGGAGGG CGGCGGTGGC CATAGCCGGC TGCTGGATCC TCTCCTTCGT GGTGGGACTG ACCCCTATGT TTGGCTGGAA CAATCTGAGT 20 GCGGTGGAGC GGGCCTGGGC AGCCAACGGC AGCATGGGGG AGCCCGTGAT CAAGTGCGAG TTCGAGAAGG TCATCAGCAT GGAGTACATG GTCTACTTCA ACTTCTTTGT GTGGGTGCTG CCCCCGCTTC TCCTCATGGT CCTCATCTAC CTGGAGGTCT TCTACCTAAT CCGCAAGCAG CTCAACAAGA AGGTGTCGGC CTCCTCCGGC GACCCGCAGA AGTACTATGG GAAGGAGCTG AAGATCGCCA AGTCGCTGGC CCTCATCCTC TTCCTCTTTG CCCTCAGCTG GCTGCCTTTG CACATCCTCA ACTGCATCAC CCTCTTCTGC CCGTCCTGCC ACAAGCCCAG 25 CATCCTTACC TACATTGCCA TCTTCCTCAC GCACGGCAAC TCGGCCATGA ACCCCATTGT CTATGCCTTC CGCATCCAGA AGTTCCGCGT CACCTTCCTT AAGATTTGGA ATGACCATTT CCGCTGCCAG CCTGCACCTC CCATTGACGA GGATCTCCCA GAAGAGAGGC CTGATGACTA G ATGAGTGTCA GAAGTGTGAA GGGTGCCTGT TCTGAATCCC AGAGCCTCCT CTCCCTCTGT GAGGCTGGCA GGTGAGGAAG GGTTTAACCT CACTGGAAGG AATCCCTGGA GCTAGCGGCT GCTGAAGGCG TCGAGGTGTG GGGGCACTTG GACAGAACAG TCAGGCAGCC 30 GGGAGCTCTG CCAGCTTTGG TGACCTGGG CCGGGCTGGG AGCGCTGCGG CGGGAGCCGG AGGACTATGA GCTGCCGCGC GTTGTCCAGA GCCCAGCCCA GCCCTACGCG CGCGGCCCGG AGCTCTGTTC CCTGGAACTT TGGGCACTGC CTCTGGGACC CCTGCCGGCC AGCAGGCAGG ATGGTGCTTG CCTCGTGCCC CTTGGTGCCC GTCTGCTGAT GTGCCCAGCC TGTGCCCGCC ATGCCGCCCT CCATCTCAGC TTTCCAGGCC GCCTACATCG GCATCGAGGT GCTCATCGCC CTGGTCTCTG TGCCCGGGAA CGTGCTGGTG ATCTGGGCGG TGAAGGTGAA 35 CCAGGCGCTG CGGGATGCCA CCTTCTGCTT CATCGTGTCG CTGGCGGTGG CTGATGTGGC CGTGGGTGCC CTGGTCATCC CCCTCGCCAT CCTCATCAAC ATTGGGCCAC AGACCTACTT CCACACCTGC CTCATGGTTG CCTGTCCGGT CCTCATCCTC ACCCAGAGCT CCATCCTGGC CCTGCTGGCA ATTGCTGTGG ACCGCTACCT CCGGGTCAAG ATCCCTCTCC GGTACAAGAT GGTGGTGACC CCCCGGAGGG CGGCGGTGGC CATAGCCGGC TGCTGGATCC TCTCCTTCGT GGTGGGACTG ACCCCTATGT TTGGCTGGAA CAATCTGAGT GCGGTGGAGC 40 GGGCCTGGGC AGCCAACGGC AGCATGGGGG AGCCCGTGAT CAAGTGCGAG TTCGAGAAGG TCATCAGCAT GGAGTACATG GTCTACTrCA ACTTCTTTGT GTGGGTGCTG CCCCCGCTTC TCCTCATGGT CCTCATCTAC CTGGAGGTCT TCTACCTAAT CCGCAAGCAG CTCAACAAGA AGGTGTCGGC CTCCTCCGGC GACCCGCAGA AGTACTATGG GAAGGAGCTG AAGATCGCCA AGTCGCTGGC CCTCATCCTC TTCCTCTTTG CCCTCAGCTG GCTGCCTTTG CACATCCTCA ACTGCATCAC CCTCTTCTGC CCGTCCTGCC ACAAGCCCAG CATCCTTACC 45 TACATTGCCA TCTTCCTCAC GCACGGCAAC TCGGCCATGA ACCCCATTGT CTATGCCTTC CGCATCCAGA AGTTCCGCGT CACCTTCCTT AAGATTTGGA ATGACCATTT CCGCTGCCAG CCTGCACCTC CCATTGACGA GGATCTCCCA GAAGAGAGGC CTGATGACTA GACCCCGCCT TCCGCTCCCA CCAGCCCACA TCCAGTGGGG TCTCAGTCCA GTCCTCACAT GCCCGCTGTC CCAGGGGTCT CCCTGAGCCT GCCCCAGCTG GGCTGTTGGC TGGGGGCATG GGGGAGGCTC TGAAGAGATA CCCACAGAGT GTGGTCCCTC CACTAGGAGT TAACTACCCT 50 ACACCTCTGG GCCCTGCAGG AGGCCTGGGA GGGCAAGGGT CCTACGGAGG GACCAGGTGT CTAGAGGCAA CAGTGTTCTG AGCCCCCACC TGCCTGACCA TCCCATGAGC AGTCCAGCGC TTCAGGGCTG GGCAGGTCCT GGGGAGGCTG AGACTGCAGA GGAGCCACCT GGGCTGGGAG AAGGTGCTTG GGCTTCTGCG GTGAGGCAGG GGAGTCTGCT TGTCTTAGAT GTTGGTGGTG CAGCCCCAGG ACCAAGCTTA AGGAGAGGAG AGCATCTGCT CTGAGACGGA TGGAAGGAGA GAGGTTGAGG ATGCACTGGC CTGTTCTGTA GGAGAGACTG GCCAGAGGCA 55 GCTAAGGGGC AGGAATCAAG GAGCCTCCGT TCCCACCTCT GAGGACTCTG GACCCCAGGC CATACCAGGT GCTAGGGTGC CTGCTCTCCT TGCCCTGGGC CAGCCCAGGA TTGTACGTGG GAGAGGCAGA AAGGGTAGGT TCAGTAATCA TTTCTGATGA TTTGCTGGAG TGCTGGCTCC ACGCCCTGGG GAGTGAGCTT GGTGCGGTAG GTGCTGGCCT CAAACAGCCA CGAGGTGGTA GCTCTGAGCC CTCCTTCTTG CCCTGAGCTT TCCGGGGAGG AGCCTGGAGT GTAATTACCT GTCATCTGGG CCACCAGCTC CACTGGCCCC CGTTGCCGGG CCTGGACTGT 60 CCTAGGTGAC CCCATCTCTG CTGCTTCTGG GCCTGATGGA GAGGAGAACA CTAGACATGC CAACTCGGGA GCATTCTGCC TGCCTGGGAA CGGGGTGGAC GAGGGAGTGT CTGTAAGGAC TCAGTGTTGA CTGTAGGCGC CCCTGGGGTG GGTTTAGCAG GCTGCAGCAG GCAGAGGAGG AGTACCCCCC TGAGAGCATG TGGGGGAAGG CCTTGCTGTC ATGTGAATCC CTCAATACCC CTAGTATCTG GCTGGGTTTT CAGGGGCTTT GGAAGCTCTG TTGCAGGTGT CCGGGGGTCT AGGACTFAG GGATCTGGGA TCTGGGGAAG GACCAACCCA TGCCCTGCCA 65 AGCCTGGAGC CCCTGTGTTG GGGGGCAAGG TGGGGGAGCC TGGAGCCCCT GTGTGGGAGG GCGAGGCGGG GGAGCCTGGA GCCCCTGTGT GGGAGGGCGA GGCGGGGGAT CCTGGAGCCC CTGTGTCGGG GGGCGAGGGA WO 00/62736 PCT/USOO/08020 103 GGGGAGGTGG CCGTCGGTTG ACCTTCTGAA CATGAGTGTC AACTCCAGGA CTTGCTTCCA AGCCCTTCCC TCTGTTGGAA ATTGGGTGTG CCCTGGCTCC CAAGGGAGGC CCATGTGACT AATAAAAAAC TGTGAACCCT CGCATTTGTG TTTTAATAAA AGAATCTGGA AGATAAATAG TCTTGAAGAG AGACAAAGGA AGGAAAATTT AAATCCTTAG ATTCAAGCAG AAGAATTCCA TGTGGAAGGT TTGGGTTGTT GTTGTTGTTG TTGGTGTGT 5 TTTTTGTTTT TTTGTTTT TGTTTTTTTT TGAGATGGAG TCTCGCTGTG TTACCGGGAG CGACAGAGCC GCACGGCCGA GTCGAGTCCC AGCCAGCTAC CATCCCTCTG GAGCTTACCG GCCGGCCTTG GCTTCCCCAG GAATCCCTGG AGCTAGCGGC TGCTGAAGGC GTCGAGGTGT GGGGGCACTT GGACAGAACA GTCAGGCAGC CGGGAGCTCT GCCAGCTTTG GTGACCTTGG GTGCTTGCCT CGTGCCCCTT GGTGCCCGTC TGCTGATGTG CCCAGCCTGT GCCCGCCATG CCGCCCTCCA TCTCAGCTTT CCAGGCCGCC TACATCGGCA TCGAGGTGCT 10 CATCGCCCTG GTCTCTGTGC CCGGGAACGT GCTGGTGATC TGGGCGGTGA AGGTGAACCA GGCGCTGCGG GATGCCACCT TCTGCTTCAT CGTGTCGCTG GCGGTGGCTG ATGTGGCCGT GGGTGCCCTG GTCATCCCCC TCGCCATCCT CATCAACATT GGGCCACAGA CCTACTTCCA CACCTGCCTC ATGGTTGCCT GTCCGGTCCT CATCCTCACC CAGAGCTCCA TCCTGGCCCT GCTGGCAATT GCTGTGGACC GCTACCTCCG GGTCAAGATC CCTCTCCGGT ACAAGATGGT GGTGACCCCC CGGAGGGCGG CGGTGGCCAT AGCCGGCTGC TGGATCCTCT 15 CCTTCGTGGT GGGACTGACC CCTATGTTTG GCTGGAACAA TCTGAGTGCG GTGGAGCGGG CCTGGGCAGC CAACGGCAGC ATGGGGGAGC CCGTGATCAA GTGCGAGTTC GAGAAGGTCA TCAGCATGGA GTACATGGTC TACTTCAACT TCTTTGTGTG GGTGCTGCCC CCGCTTCTCC TCATGGTCCT CATCTACCTG GAGGTCTTICT ACCTAATCCG CAAGCAGCTC AACAAGAAGG TGTCGGCCTC CTCCGGCGAC CCGCAGAAGT ACTATGGGAA GGAGCTGAAG ATCGCCAAGT CGCTGGCCCT CATCCTCTTC CTCTTTGCCC TCAGCTGGCT GCCTTTGCAC 20 ATCCTCAACT GCATCACCCT CTTCTGCCCG TCCTGCCACA AGCCCAGCAT CCTTACCTAC ATTGCCATCT TCCTCACGCA CGGCAACTCG GCCATGAACC CCATTGTCTA TGCCTTCCGC ATCCAGAAGT TCCGCGTCAC CTTCCTTAAG ATTTGGAATG ACCATTTCCG CTGCCAGCCT GCACCTCCCA TTGACGAGGA TCTCCCAGAA GAGAGGCCTG ATGACTAGAC CCCGCCTTCC GCTCCCACCG CCCACATCCA GTGGGGTCTC AGTCCAGTCC TCACATGCCC GCTGTCCCAG GGGTCTCCCT GAGCCTGCCC CAGCTGGGCT GTTGGCTGGG GGCATGGGGG 25 AGGCTCTGAA GAGATACCCA CAGAGTGTGG TCCCTCCACT AGGAGTTAAC TACCCTACAC CTCTGGGCCC TGCAGGAGGC CTGGGAGGGC AAGGGTCCTA CGGAGGGACC AGGTGTCTAG AGGCAACAGT GTTCTGAGCC CCCACCTGCC TGACCATCCC ATGAGCAGTC CAGAGCTTCA GGGCTGGGCA GGTCCTGGGG AGGCTGAGAC TGCAGAGGAG CCACCTGGGC TGGGAGAAGG TGCTTGGGCT TCTGCGGTGA GGCAGGGGAG TCTGCTTGTC TTAGATGTTG GTGGTGCAGC CCCAGGACCA AGCTTAAGGA GAGGAGAGCA TCTGCTCTGA GACGGATGGA 30 AGGAGAGAGG TTGAGGATGC ACTGGCCTGT TCTGTAGGAG AGACTGGCCA GA 3'(FRAG.NO:_)(SEQ.NO:3005) [2423)] 5'-CGCATTTGTG TTTTAATAAA AGAATCTGGA AGATAAATAG TCTTGAAGAG AGACAAAGGA AGGAAAATTT AAATCCTTAG ATTCAAGCAG AAGAATTCCA TGTGGAAGGT TrGGGTTGTTr GTTGTTGTTG TTTGGTGTGT T'TTGTTTT TTTGTTTTTT TGTTTTT TGAGATGGAG TCTCGCTGTG TTACCGGGAG CGACAGAGCC 35 GCACGGCCGA GTCGAGTCCC AGCCAGCTAC CATCCCTCTG GAGCTTACCG GCCGGCCTTG GCTTCCCCAG GAATCCCTGG AGCTAGCGGC TGCTGAAGGC GTCGAGGTGT GGGGGCACTT GGACAGAACA GTCAGGCAGC CGGGAGCTCT GCCAGCTTTG GTGACCTTGG GTGCTTGCCT CGTGCCCCTT GGTGCCCGTC TGCTGATGTG CCCAGCCTGT GCCCGCCATG CCGCCCTCCA TCTCAGCTTT CCAGGCCGCC TACATCGGCA TCGAGGTGCT CATCGCCCTG GTCTCTGTGC CCGGGAACGT GCTGGTGATC TGGGCGGTGA AGGTGAACCA GGCGCTGCGG 40 GATGCCACCT TCTGCTTCAT CGTGTCGCTG GCGGTGGCTG ATGTGGCCGT GGGTGCCCTG GTCATCCCCC TCGCCATCCT CATCAACATT GGGCCACAGA CCTACTTCCA CACCTGCCTC ATGGTTGCCT GTCCGGTCCT CATCCTCACC CAGAGCTCCA TCCTGGCCCT GCTGGCAATT GCTGTGGACC GCTACCTCCG GGTCAAGATC CCTCTCCGGT ACAAGATGGT GGTGACCCCC CGGAGGGCGG CGGTGGCCAT AGCCGGCTGC TGGATCCTCT CCTTCGTGGT GGGACTGACC CCTATGTTTG GCTGGAACAA TCTGAGTGCG GTGGAGCGGG CCTGGGCAGC 45 CAACGGCAGC ATGGGGGAGC CCGTGATCAA GTGCGAGTTC GAGAAGGTCA TCAGCATGGA GTACATGGTC TACTTCAACT TCTTTGTGTG GGTGCTGCCC CCGCTTCTCC TCATGGTCCT CATCTACCTG GAGGTCTITCT ACCTAATCCG CAAGCAGCTC AACAAGAAGG TGTCGGCCTC CTCCGGCGAC CCGCAGAAGT ACTATGGGAA GGAGCTGAAG ATCGCCAAGT CGCTGGCCCT CATCCTCTTC CTCTTTGCCC TCAGCTGGCT GCCTTTGCAC ATCCTCAACT GCATCACCCT CTTCTGCCCG TCCTGCCACA AGCCCAGCAT CCTTACCTAC ATTGCCATCT 50 TCCTCACGCA CGGCAACTCG GCCATGAACC CCATTGTCTA TGCCTTCCGC ATCCAGAAGT TCCGCGTCAC CTTCCTTAAG ATTTGGAATG ACCATTTCCG CTGCCAGCCT GCACCTCCCA TTGACGAGGA TCTCCCAGAA GAGAGGCCTG ATGACTAGAC CCCGCCTTCC GCTCCCACCG CCCACATCCA GTGGGGTCTC AGTCCAGTCC TCACATGCCC GCTGTCCCAG GGGTCTCCCT GAGCCTGCCC CAGCTGGGCT GTTGGCTGGG GGCATGGGGG AGGCTCTGAA GAGATACCCA CAGAGTGTGG TCCCTCCACT AGGAGTTAAC TACCCTACAC CTCTGGGCCC 55 TGCAGGAGGC CTGGGAGGGC AAGGGTCCTA CGGAGGGACC AGGTGTCTAG AGGCAACAGT GTTCTGAGCC CCCACCTGCC TGACCATCCC ATGAGCAGTC CAGAGCTTCA GGGCTGGGCA GGTCCTGGGG AGGCTGAGAC TGCAGAGGAG CCACCTGGGC TGGGAGAAGG TGCTTGGGCT TCTGCGGTGA GGCAGGGGAG TCTGCTrGTC TTAGATGTTG GTGGTGCAGC CCCAGGACCA AGCTTAAGGA GAGGAGAGCA TCTGCTCTGA GACGGATGGA AGGAGAGAGG TTGAGGATGC ACTGGCCTGT TCTGTAGGAG AGACTGGCCA GA -3' (FRAG. NO: )(SEQ. ID 60 NO: 2434) 5'- ATGAGTGTCA GAAGTGTGAA GGGTGCCTGT TCTGAATCCC AGAGCCTCCT CTCCCTCTGT GAGGCTGGCA GGTGAGGAAG GGTTTAACCT CACTGGAAGG AATCCCTGGA GCTAGCGGCT GCTGAAGGCG TCGAGGTGTG GGGGCACTTG GACAGAACAG TCAGGCAGCC GGGAGCTCTG CCAGCTTTGG TGACCTTGGG CCGGGCTGGG AGCGCTGCGG CGGGAGCCGG AGGACTATGA GCTGCCGCGC GTTGTCCAGA GCCCAGCCCA GCCCTACGCG 65 CGCGGCCCGG AGCTCTGTTC CCTGGAACTT TGGGCACTGC CTCTGGGACC CCTGCCGGCC AGCAGGCAGG ATGGTGCTTG CCTCGTGCCC CTTGGTGCCC GTCTGCTGAT GTGCCCAGCC TGTGCCCGCC ATGCCGCCCT WO 00/62736 PCT/USOO/08020 104 CCATCTCAGC TTTCCAGGCC GCCTACATCG GCATCGAGGT GCTCATCGCC CTGGTCTCTG TGCCCGGGAA CGTGCTGGTG ATCTGGGCGG TGAAGGTGAA CCAGGCGCTG CGGGATGCCA CCTTCTGCTT CATCGTGTCG CTGGCGGTGG CTGATGTGGC CGTGGGTGCC CTGGTCATCC CCCTCGCCAT CCTCATCAAC ATTGGGCCAC AGACCTACTT CCACACCTGC CTCATGGTTG CCTGTCCGGT CCTCATCCTC ACCCAGAGCT CCATCCTGGC 5 CCTGCTGGCA ATTGCTGTGG ACCGCTACCT CCGGGTCAAG ATCCCTCTCC GGTACAAGAT GGTGGTGACC CCCCGGAGGG CGGCGGTGGC CATAGCCGGC TGCTGGATCC TCTCCTTCGT GGTGGGACTG ACCCCTATGT TTGGCTGGAA CAATCTGAGT GCGGTGGAGC GGGCCTGGGC AGCCAACGGC AGCATGGGGG AGCCCGTGAT CAAGTGCGAG -TCGAGAAGG TCATCAGCAT GGAGTACATG GTCTACTTCA ACTTCTTTGT GTGGGTGCTG CCCCCGCTTC TCCTCATGGT CCTCATCTAC CTGGAGGTCT TCTACCTAAT CCGCAAGCAG CTCAACAAGA 10 AGGTGTCGGC CTCCTCCGGC GACCCGCAGA AGTACTATGG GAAGGAGCTG AAGATCGCCA AGTCGCTGGC CCTCATCCTC TTCCTCTTTG CCCTCAGCTG GCTGCCTTTG CACATCCTCA ACTGCATCAC CCTCTTCTGC CCGTCCTGCC ACAAGCCCAG CATCCTTACC TACATTGCCA TCTTCCTCAC GCACGGCAAC TCGGCCATGA ACCCCATTGT CTATGCCTTC CGCATCCAGA AGTTCCGCGT CACCTTCCTT AAGATTTGGA ATGACCATTT CCGCTGCCAG CCTGCACCTC CCATTGACGA GGATCTCCCA GAAGAGAGGC CTGATGACTA GACCCCGCCT 15 TCCGCTCCCA CCAGCCCACA TCCAGTGGGG TCTCAGTCCA GTCCTCACAT GCCCGCTGTC CCAGGGGTCT CCCTGAGCCT GCCCCAGCTG GGCTGT'TGGC TGGGGGCATG GGGGAGGCTC TGAAGAGATA CCCACAGAGT GTGGTCCCTC CACTAGGAGT TAACTACCCT ACACCTCTGG GCCCTGCAGG AGGCCTGGGA GGGCAAGGGT CCTACGGAGG GACCAGGTGT CTAGAGGCAA CAGTGTTCTG AGCCCCCACC TGCCTGACCA TCCCATGAGC AGTCCAGCGC TTCAGGGCTG GGCAGGTCCT GGGGAGGCTG AGACTGCAGA GGAGCCACCT GGGCTGGGAG 20 AAGGTGCTTG GGCTTCTGCG GTGAGGCAGG GGAGTCTGCT TGTCTTAGAT GTTGGTGGTG CAGCCCCAGG ACCAAGCTTA AGGAGAGGAG AGCATCTGCT CTGAGACGGA TGGAAGGAGA GAGGTTGAGG ATGCACTGGC CTGTTCTGTA GGAGAGACTG GCCAGAGGCA GCTAAGGGGC AGGAATCAAG GAGCCTCCGT TCCCACCTCT GAGGACTCTG GACCCCAGGC CATACCAGGT GCTAGGGTGC CTGCTCTCCT TGCCCTGGGC CAGCCCAGGA TTGTACGTGG GAGAGGCAGA AAGGGTAGGT TCAGTAATCA TTTCTGATGA TTTGCTGGAG TGCTGGCTCC 25 ACGCCCTGGG GAGTGAGCTT GGTGCGGTAG GTGCTGGCCT CAAACAGCCA CGAGGTGGTA GCTCTGAGCC CTCCTTCTTG CCCTGAGCTT TCCGGGGAGG AGCCTGGAGT GTAATTACCT GTCATCTGGG CCACCAGCTC CACTGGCCCC CGTTGCCGGG CCTGGACTGT CCTAGGTGAC CCCATCTCTG CTGCTTCTGG GCCTGATGGA GAGGAGAACA CTAGACATGC CAACTCGGGA GCATTCTGCC TGCCTGGGAA CGGGGTGGAC GAGGGAGTGT CTGTAAGGAC TCAGTGTTGA CTGTAGGCGC CCCTGGGGTG GGTTTAGCAG GCTGCAGCAG GCAGAGGAGG 30 AGTACCCCCC TGAGAGCATG TGGGGGAAGG CCTTGCTGTC ATGTGAATCC CTCAATACCC CTAGTATCTG GCTGGGTTT CAGGGGCTTT GGAAGCTCTG TTGCAGGTGT CCGGGGGTCT AGGACTTTAG GGATCTGGGA TCTGGGGAAG GACCAACCCA TGCCCTGCCA AGCCTGGAGC CCCTGTGTTG GGGGGCAAGG TGGGGGAGCC TGGAGCCCCT GTGTGGGAGG GCGAGGCGGG GGAGCCTGGA GCCCCTGTGT GGGAGGGCGA GGCGGGGGAT CCTGGAGCCC CTGTGTCGGG GGGCGAGGGA GGGGAGGTGG CCGTCGGTTG ACCTTCTGAA CATGAGTGTC 35 AACTCCAGGA CTTGCTTCCA AGCCCTTCCC TCTGTTGGAA ATTGGGTGTG CCCTGGCTCC CAAGGGAGGC CCATGTGACT AATAAAAAAC TGTGAACCCT -3' (FRAG. NO:_)(SEQ. ID NO: 2433) 5'- ATGCCGCCCT CCATCTCAGC TITCCAGGCC GCCTACATCG GCATCGAGGT GCTCATCGCC CTGGTCTCTG TGCCCGGGAA CGTGCTGGTG ATCTGGGCGG TGAAGGTGAA CCAGGCGCTG CGGGATGCCA CCTTCTGCTT CATCGTCTCG CTGGCGGTGG CTGATGTGGC CGTGGGTGCC CTGGTCATCC CCCTCGCCAT CCTCATCAAC 40 ATrGGGCCAC AGACCTACTT CCACACCTGC CTCATGGTTG CCTGTCCGGT CCTCATCCTC ACCCAGAGCT CCATCCTGGC CCTGCTGGCA ATTGCTGTGG ACCGCTACCT CCGGGTCAAG ATCCCTCTCC GGTACAAGAT GGTGGTGACC CCCCGGAGGG CGGCGGTGGC CATAGCCGGC TGCTGGATCC TCTCCTTCGT GGTGGGACTG ACCCCTATGT TTGGCTGGAA CAATCTGAGT GCGGTGGAGC GGGCCTGGGC AGCCAACGGC AGCATGGGGG AGCCCGTGAT CAAGTGCGAG TTCGAGAAGG TCATCAGCAT GGAGTACATG GTCTACTTCA ACTTCTTTGT 45 GTGGGTGCTG CCCCCGCTTC TCCTCATGGT CCTCATCTAC CTGGAGGTCT TCTACCTAAT CCGCAAGCAG CTCAACAAGA AGGTGTCGGC CTCCTCCGGC GACCCGCAGA AGTACTATGG GAAGGAGCTG AAGATCGCCA AGTCGCTGGC CCTCATCCTC TTCCTCTTG CCCTCAGCTG GCTGCCTTTG CACATCCTCA ACTGCATCAC CCTCTTCTGC CCGTCCTGCC ACAAGCCCAG CATCCTTACC TACATTGCCA TCTTCCTCAC GCACGGCAAC TCGGCCATGA ACCCCATTGT CTATGCCTTC CGCATCCAGA AGTTCCGCGT CACCTTCCTT AAGA'TGGA 50 ATGACCATTT CCGCTGCCAG CCTGCACCTC CCATTGACGA GGATCTCCCA GAAGAGAGGC CTGATGACTA G 3' (FRAG. NO:_)(SEQ. ID NO: 2432) 5'-CGCATTrGTG TTTTAATAAA AGAATCTGGA AGATAAATAG TCTTGAAGAG AGACAAAGGA AGGAAAATTT AAATCCT'TAG ATTCAAGCAG AAGAATTCCA TGTGGAAGGT TTGGGTTGTT GTTGTTGTTG TTGGTGTGT TTTTGTTTT TTGTTTIT TGTTTTTTT TGAGATGGAG TCTCGCTGTG TTACCGGGAG CGACAGAGCC 55 GCACGGCCGA GTCGAGTCCC AGCCAGCTAC CATCCCTCTG GAGCTTACCG GCCGGCCTTG GCTTCCCCAG GAATCCCTGG AGCTAGCGGC TGCTGAAGGC GTCGAGGTGT GGGGGCACTT GGACAGAACA GTCAGGCAGC CGGGAGCTCT GCCAGCTTTG GTGACCTTGG GTGCTTGCCT CGTGCCCCTT GGTGCCCGTC TGCTGATGTG CCCAGCCTGT GCCCGCCATG CCGCCCTCCA TCTCAGCTTT CCAGGCCGCC TACATCGGCA TCGAGGTGCT CATCGCCCTG GTCTCTGTGC CCGGGAACGT GCTGGTGATC TGGGCGGTGA AGGTGAACCA GGCGCTGCGG 60 GATGCCACCT TCTGCTTCAT CGTGTCGCTG GCGGTGGCTG ATGTGGCCGT GGGTGCCCTG GTCATCCCCC TCGCCATCCT CATCAACATT GGGCCACAGA CCTACTTCCA CACCTGCCTC ATGGTTGCCT GTCCGGTCCT CATCCTCACC CAGAGCTCCA TCCTGGCCCT GCTGGCAATT GCTGTGGACC GCTACCTCCG GGTCAAGATC CCTCTCCGGT ACAAGATGGT GGTGACCCCC CGGAGGGCGG CGGTGGCCAT AGCCGGCTGC TGGATCCTCT CCTTCGTGGT GGGACTGACC CCTATGTTTG GCTGGAACAA TCTGAGTGCG GTGGAGCGGG CCTGGGCAGC 65 CAACGGCAGC ATGGGGGAGC CCGTGATCAA GTGCGAGTTC GAGAAGGTCA TCAGCATGGA GTACATGGTC TACTTCAACT TCTTTGTGTG GGTGCTGCCC CCGCTTCTCC TCATGGTCCT CATCTACCTG GAGGTCTTCT WO 00/62736 PCT/USOO/08020 105 ACCTAATCCG CAAGCAGCTC AACAAGAAGG TGTCGGCCTC CTCCGGCGAC CCGCAGAAGT ACTATGGGAA GGAGCTGAAG ATCGCCAAGT CGCTGGCCCT CATCCTCTTC CTCTTTGCCC TCAGCTGGCT GCCTTTGCAC ATCCTCAACT GCATCACCCT CTTCTGCCCG TCCTGCCACA AGCCCAGCAT CCTTACCTAC ATTGCCATCT TCCTCACGCA CGGCAACTCG GCCATGAACC CCATTGTCTA TGCCTTCCGC ATCCAGAAGT TCCGCGTCAC 5 CTTCCTTAAG ATTTGGAATG ACCATTTCCG CTGCCAGCCT GCACCTCCCA TTGACGAGGA TCTCCCAGAA GAGAGGCCTG ATGACTAGAC CCCGCCTTCC GCTCCCACCG CCCACATCCA GTGGGGTCTC AGTCCAGTCC TCACATGCCC GCTGTCCCAG GGGTCTCCCT GAGCCTGCCC CAGCTGGGCT GTTGGCTGGG GGCATGGGGG AGGCTCTGAA GAGATACCCA CAGAGTGTGG TCCCTCCACT AGGAGTTAAC TACCCTACAC CTCTGGGCCC TGCAGGAGGC CTGGGAGGGC AAGGGTCCTA CGGAGGGACC AGGTGTCTAG AGGCAACAGT GTTCTGAGCC 10 CCCACCTGCC TGACCATCCC ATGAGCAGTC CAGAGCTTCA GGGCTGGGCA GGTCCTGGGG AGGCTGAGAC TGCAGAGGAG CCACCTGGGC TGGGAGAAGG TGCTTGGGCT TCTGCGGTGA GGCAGGGGAG TCTGCTTGTC TTAGATGTTG GTGGTGCAGC CCCAGGACCA AGCTTAAGGA GAGGAGAGCA TCTGCTCTGA GACGGATGGA AGGAGAGAGG TTGAGGATGC ACTGGCCTGT TCTGTAGGAG AGACTGGCCA GA -3' (FRAG. NO:_)(SEQ. ID NO: 2422) 15 5'-ATGAGTGTCA GAAGTGTGAA GGGTGCCTGT TCTGAATCCC AGAGCCTCCT CTCCCTCTGT GAGGCTGGCA GGTGAGGAAG GGTTAACCT CACTGGAAGG AATCCCTGGA GCTAGCGGCT GCTGAAGGCG TCGAGGTGTG GGGGCACTTG GACAGAACAG TCAGGCAGCC GGGAGCTCTG CCAGCTTTGG TGACCTTGGG CCGGGCTGGG AGCGCTGCGG CGGGAGCCGG AGGACTATGA GCTGCCGCGC GTTGTCCAGA GCCCAGCCCA GCCCTACGCG CGCGGCCCGG AGCTCTGTTC CCTGGAACTT TGGGCACTGC CTCTGGGACC CCTGCCGGCC AGCAGGCAGG 20 ATGGTGCTTG CCTCGTGCCC CTTGGTGCCC GTCTGCTGAT GTGCCCAGCC TGTGCCCGCC ATGCCGCCCT CCATCTCAGC TTTCCAGGCC GCCTACATCG GCATCGAGGT GCTCATCGCC CTGGTCTCTG TGCCCGGGAA CGTGCTGGTG ATCTGGGCGG TGAAGGTGAA CCAGGCGCTG CGGGATGCCA CCTTCTGCTT CATCGTGTCG CTGGCGGTGG CTGATGTGGC CGTGGGTGCC CTGGTCATCC CCCTCGCCAT CCTCATCAAC ATTGGGCCAC AGACCTACTT CCACACCTGC CTCATGGTTG CCTGTCCGGT CCTCATCCTC ACCCAGAGCT CCATCCTGGC 25 CCTGCTGGCA ATTGCTGTGG ACCGCTACCT CCGGGTCAAG ATCCCTCTCC GGTACAAGAT GGTGGTGACC CCCCGGAGGG CGGCGGTGGC CATAGCCGGC TGCTGGATCC TCTCCTTCGT GGTGGGACTG ACCCCTATGT TTGGCTGGAA CAATCTGAGT GCGGTGGAGC GGGCCTGGGC AGCCAACGGC AGCATGGGGG AGCCCGTGAT CAAGTGCGAG TTCGAGAAGG TCATCAGCAT GGAGTACATG GTCTACTTCA ACTTCTTTGT GTGGGTGCTG CCCCCGCTTC TCCTCATGGT CCTCATCTAC CTGGAGGTCT TCTACCTAAT CCGCAAGCAG CTCAACAAGA 30 AGGTGTCGGC CTCCTCCGGC GACCCGCAGA AGTACTATGG GAAGGAGCTG AAGATCGCCA AGTCGCTGGC CCTCATCCTC TTCCTCTTTG CCCTCAGCTG GCTGCCTTTG CACATCCTCA ACTGCATCAC CCTCTTCTGC CCGTCCTGCC ACAAGCCCAG CATCCTTACC TACATTGCCA TCTrCCTCAC GCACGGCAAC TCGGCCATGA ACCCCATTGT CTATGCCTTC CGCATCCAGA AGTTCCGCGT CACCTTCCTT AAGATTTGGA ATGACCATTT CCGCTGCCAG CCTGCACCTC CCATTGACGA GGATCTCCCA GAAGAGAGGC CTGATGACTA GACCCCGCCT 35 TCCGCTCCCA CCAGCCCACA TCCAGTGGGG TCTCAGTCCA GTCCTCACAT GCCCGCTGTC CCAGGGGTCT CCCTGAGCCT GCCCCAGCTG GGCTGTTGGC TGGGGGCATG GGGGAGGCTC TGAAGAGATA CCCACAGAGT GTGGTCCCTC CACTAGGAGT TAACTACCCT ACACCTCTGG GCCCTGCAGG AGGCCTGGGA GGGCAAGGGT CCTACGGAGG GACCAGGTGT CTAGAGGCAA CAGTGTTCTG AGCCCCCACC TGCCTGACCA TCCCATGAGC AGTCCAGCGC TTCAGGGCTG GGCAGGTCCT GGGGAGGCTG AGACTGCAGA GGAGCCACCT GGGCTGGGAG 40 AAGGTGCTTG GGCTTCTGCG GTGAGGCAGG GGAGTCTGCT TGTCTTAGAT GTTGGTGGTG CAGCCCCAGG ACCAAGCTTA AGGAGAGGAG AGCATCTGCT CTGAGACGGA TGGAAGGAGA GAGGTrGAGG ATGCACTGGC CTGTTCTGTA GGAGAGACTG GCCAGAGGCA GCTAAGGGGC AGGAATCAAG GAGCCTCCGT TCCCACCTCT GAGGACTCTG GACCCCAGGC CATACCAGGT GCTAGGGTGC CTGCTCTCCT TGCCCTGGGC CAGCCCAGGA TTGTACGTGG GAGAGGCAGA AAGGGTAGGT TCAGTAATCA TTTCTGATGA TTTGCTGGAG TGCTGGCTCC 45 ACGCCCTGGG GAGTGAGCTT GGTGCGGTAG GTGCTGGCCT CAAACAGCCA CGAGGTGGTA GCTCTGAGCC CTCCTTCTTG CCCTGAGCTT TCCGGGGAGG AGCCTGGAGT GTAATTACCT GTCATCTGGG CCACCAGCTC CACTGGCCCC CGTTGCCGGG CCTGGACTGT CCTAGGTGAC CCCATCTCTG CTGCTTCTGG GCCTGATGGA GAGGAGAACA CTAGACATGC CAACTCGGGA GCATTCTGCC TGCCTGGGAA CGGGGTGGAC GAGGGAGTGT CTGTAAGGAC TCAGTGTTGA CTGTAGGCGC CCCTGGGGTG GGTTTAGCAG GCTGCAGCAG GCAGAGGAGG 50 AGTACCCCCC TGAGAGCATG TGGGGGAAGG CCTTGCTGTC ATGTGAATCC CTCAATACCC CTAGTATCTG GCTGGGTTTT CAGGGGCTTT GGAAGCTCTG TTGCAGGTGT CCGGGGGTCT AGGACTTTAG GGATCTGGGA TCTGGGGAAG GACCAACCCA TGCCCTGCCA AGCCTGGAGC CCCTGTGTTG GGGGGCAAGG TGGGGGAGCC TGGAGCCCCT GTGTGGGAGG GCGAGGCGGG GGAGCCTGGA GCCCCTGTGT GGGAGGGCGA GGCGGGGGAT CCTGGAGCCC CTGTGTCGGG GGGCGAGGGA GGGGAGGTGG CCGTCGGTTG ACCT'TCTGAA CATGAGTGTC 55 AACTCCAGGA CTTGCTTCCA AGCCCTTCCC TCTGTTGGAA ATTGGGTGTG CCCTGGCTCC CAAGGGAGGC CCATGTGACT AATAAAAAAC TGTGAACCCT -3' (FRAG. NO:__) (SEQ. ID NO: 2421) 5'-ATGCCGCCCT CCATCTCAGC TTTCCAGGCC GCCTACATCG GCATCGAGGT GCTCATCGCC CTGGTCTCTG TGCCCGGGAA CGTGCTGGTG ATCTGGGCGG TGAAGGTGAA CCAGGCGCTG CGGGATGCCA CCTTCTGCTT CATCGTCTCG CTGGCGGTGG CTGATGTGGC CGTGGGTGCC CTGGTCATCC CCCTCGCCAT CCTCATCAAC 60 ATTGGGCCAC AGACCTACTT CCACACCTGC CTCATGGTTG CCTGTCCGGT CCTCATCCTC ACCCAGAGCT CCATCCTGGC CCTGCTGGCA ATTGCTGTGG ACCGCTACCT CCGGGTCAAG ATCCCTCTCC GGTACAAGAT GGTGGTGACC CCCCGGAGGG CGGCGGTGGC CATAGCCGGC TGCTGGATCC TCTCCTTCGT GGTGGGACTG CCCCTATGT TTGGCTGGAA CAATCTGAGT GCGGTGGAGC GGGCCTGGGC AGCCAACGGC AGCATGGGGG AGCCCGTGAT CAAGTGCGAG TTCGAGAAGG TCATCAGCAT GGAGTACATG GTCTACTTCA ACTTCTTTGT 65 GTGGGTGCTG CCCCCGCTTC TCCTCATGGT CCTCATCTAC CTGGAGGTCT TCTACCTAAT CCGCAAGCAG CTCAACAAGA AGGTGTCGGC CTCCTCCGGC GACCCGCAGA AGTACTATGG GAAGGAGCTG AAGATCGCCA WO 00/62736 PCT/USOO/08020 106 AGTCGCTGGC CCTCATCCTC TTCCTCTTTG CCCTCAGCTG GCTGCCTTTG CACATCCTCA ACTGCATCAC CCTCTTCTGC CCGTCCTGCC ACAAGCCCAG CATCCTTACC TACATTGCCA TCTTCCTCAC GCACGGCAAC TCGGCCATGA ACCCCATTGT CTATGCCTTC CGCATCCAGA AGTTCCGCGT CACCTTCCTT AAGATTTGGA ATGACCATT CCGCTGCCAG CCTGCACCTC CCATTGACGA GGATCTCCCA GAAGAGAGGC CTGATGACTA G 5 (FRAG NO: _) (SEQ. ID NO: 2420) 5'-GAT GGA GGG CGG CAT GGC GGG-3' (FRAG. NO: 1657) (SEQ ID NO:2412) 5'-G CGG GTC GCC GG-3' (FRAG. NO: 1658) (SEQ ID NO:2413) 5'-GGC GGG CBC BGG C-3' (FRAG. NO: 1659) (SEQ ID NO:2414) 5'-GGC GGG CBC-3' (FRAG. NO: 1660) (SEQ ID NO:2415) 10 5'-GC GGC CTG G-3' (FRAG. NO: 1661) (SEQ ID NO:2416) 5'-GGB GGG CGG C-3' (FRAG. NO: 1662) (SEQ ID NO:2417) 5'-GBT GGB GGG-3' (FRAG. NO: 1663) (SEQ ID NO:2418) 5'-GG CTG GGC-3' (FRAG. NO: 1664) (SEQ ID NO:2419) 5'-GC GGC CTG GAA AGC TGA GAT GGA GGG CGG CAT GGC GGG CAC AGG CTG GGC-3' (FRAG.1) (SEQ. ID NO: 11) 15 5'-C GGC CTG GAA AGC TGA GAT GGA GGG CGG CAT GGC GGG CAC AGG CTG GGC-3'(FRAG 2) (SEQ. .ID NO:12) 5'-GGC CTG GAA AGC TGA GAT GGA GGG CGG CAT GGC GGG CAC AGG CTG GGC-3'(FRAG 3)(SEQ.ID NO:13) 5'-GC CTG GAA AGC TGA GAT GGA GGG CGG CAT GGC GGG CAC AGG CTG GGC-3' (FRAG 4)(SEQ. ID NO:14) 5'-C CTG GAA AGC TGA GAT GGA GGG CGG CAT GGC GGG CAC AGG CTG GGC-3' (FRAG 5) (SEQ. ID NO: 15) 20 5'-CTG GAA AGC TGA GAT GGA GGG CGG CAT GGC GGG CAC AGG CTG GGC-3' (FRAG 6) (SEQ. ID NO: 16) 5'-TG GAA AGC TGA GAT GGA GGG CGG CAT GGC GGG CAC AGG CTG GGC-3' (FRAG 7) (SEQ. ID NO: 17) 5'-G GAA AGC TGA GAT GGA GGG CGG CAT GGC GGG CAC AGG CTG GGC-3' (FRAG 8) (SEQ. ID NO: 18) 5'-GAA AGC TGA GAT GGA GGG CGG CAT GGC GGG CAC AGG CTG GGC-3' (FRAG 9) (SEQ. ID NO: 19) 5'-AA AGC TGA GAT GGA GGG CGG CAT GGC GGG CAC AGG CTG GGC-3' (FRAG 10) (SEQ. ID NO: 20) 25 5'-A AGC TGA GAT GGA GGG CGG CAT GGC GGG CAC AGG CTG GGC-3' (FRAG 11) (SEQ. ID NO: 21) 5'-AGC TGA GAT GGA GGG CGG CAT GGC GGG CAC AGG CTG GGC-3' (FRAG 12) (SEQ. ID NO: 22) 5'-GC TGA GAT GGA GGG CGG CAT GGC GGG CAC AGG CTG GGC-3' (FRAG 13) (SEQ. ID NO: 23) 5'-C TGA GAT GGA GGG CGG CAT GGC GGG CAC AGG CTG GGC-3' (FRAG 14) (SEQ. ID NO: 24) 5'-TGA GAT GGA GGG CGG CAT GGC GGG CAC AGG CTG GGC-3' (FRAG 15) (SEQ. ID NO: 25) 30 5'-GA GAT GGA GGG CGG CAT GGC GGG CAC AGG CTG GGC-3' (FRAG 16) (SEQ. ID NO: 26) 5'-A GAT GGA GGG CGG CAT GGC GGG CAC AGG CTG GGC-3' (FRAG 17) (SEQ. ID NO: 27) 5'-GAT GGA GGG CGG CAT GGC GGG CAC AGG CTG GGC-3' (FRAG 18) (SEQ. ID NO: 28) 5'-AT GGA GGG CGG CAT GGC GGG CAC AGG CTG GGC-3' (FRAG 19) (SEQ. ID NO: 29) 5'-T GGA GGG CGG CAT GGC GGG CAC AGG CTG GGC-3' (FRAG 20) (SEQ. ID NO: 30) 35 5'-GGA GGG CGG CAT GGC GGG CAC AGG CTG GGC-3' (FRAG 21) (SEQ. ID NO: 31) 5'-GA GGG CGG CAT GGC GGG CAC AGG CTG GGC-3' (FRAG 22) (SEQ. ID NO: 32) 5'-A GGG CGG CAT GGC GGG CAC AGG CTG GGC-3' (FRAG 23) (SEQ. ID NO: 33) 5'-GGG CGG CAT GGC GGG CAC AGG CTG GGC-3' (FRAG 24) (SEQ. ID NO: 34) 5'-GG CGG CAT GGC GGG CAC AGG CTG GGC-3' (FRAG 25) (SEQ. ID NO: 35) 40 5'-G CGG CAT GGC GGG CAC AGG CTG GGC-3' (FRAG 26) (SEQ. ID NO: 36) 5'-CGG CAT GGC GGG CAC AGG CTG GGC-3' (FRAG 27) (SEQ. ID NO: 37) 5'-GG CAT GGC GGG CAC AGG CTG GGC-3' (FRAG 28) (SEQ. ID NO: 38) 5'-G CAT GGC GGG CAC AGG CTG GGC-3' (FRAG 29) (SEQ. ID NO: 39) 5'-CAT GGC GGG CAC AGG CTG GGC-3' (FRAG 30) (SEQ. ID NO: 40) 45 5'-AT GGC GGG CAC AGG CTG GGC-3' (FRAG 31) (SEQ. ID NO: 41) 5'-T GGC GGG CAC AGG CTG GGC-3' (FRAG 32) (SEQ. ID NO: 42) 5'-GGC GGG CAC AGG CTG GGC-3' (FRAG 33) (SEQ. ID NO: 43) 5'-GC GGG CAC AGG CTG GGC-3' (FRAG 34) (SEQ. ID NO: 44) 5'-C GGG CAC AGG CTG GGC-3' (FRAG 35) (SEQ. ID NO: 45) 50 5'-GGG CAC AGG CTG GGC-3' (FRAG 36) (SEQ. ID NO: 46) 5'-GG CAC AGG CTG GGC-3' (FRAG 37) (SEQ. ID NO: 47) 5'-G CAC AGG CTG GGC-3' (FRAG 38) (SEQ. ID NO: 48) 5'-CAC AGG CTG GGC-3' (FRAG 39) (SEQ. ID NO: 49) 5'-AC AGG CTG GGC-3' (FRAG 40) (SEQ. ID NO: 50) 55 5'-C AGG CTG GGC-3' (FRAG 41) (SEQ. ID NO: 51) 5'-AGG CTG GGC-3' (FRAG 42) (SEQ. ID NO: 52) 5'-GGC GGC CTG GAA AGC TGA GAT GGA GGG CGG CAT GGC GGG CAC AGG CTG GGC-3'(FRAG 43)(SEQ.ID NO:53) 5'-GGC GGC CTG GAA AGC TGA GAT GGA GGG CGG CAT GGC GGG CAC AGG CTG GG-3' (FRAG 44)(SEQ.ID NO:54) 5'-GGC GGC CTG GAA AGC TGA GAT GGA GGG CGG CAT GGC GGG CAC AGG CTG G-3' (FRAG 45)(SEQ.ID NO:55) 60 5'-GGC GGC CTG GAA AGC TGA GAT GGA GGG CGG CAT GGC GGG CAC AGG CTG -3' (FRAG 46)(SEQ.ID NO:56) 5'-GGC GGC CTG GAA AGC TGA GAT GGA GGG CGG CAT GGC GGG CAC AGG CT-3' (FRAG 47)(SEQ.ID NO:57) 5'-GGC GGC CTG GAA AGC TGA GAT GGA GGG CGG CAT GGC GGG CAC AGG C-3' (FRAG 48)(SEQ. ID NO:58) 5'-GGC GGC CTG GAA AGC TGA GAT GGA GGG CGG CAT GGC GGG CAC AGG -3' (FRAG 49) (SEQ. ID NO: 59) 5'-GGC GGC CTG GAA AGC TGA GAT GGA GGG CGG CAT GGC GGG CAC AG-3' (FRAG 50) (SEQ. ID NO: 60) 65 5'-GGC GGC CTG GAA AGC TGA GAT GGA GGG CGG CAT GGC GGG CAC A-3' (FRAG 51) (SEQ. ID NO: 61) 5'-GGC GGC CTG GAA AGC TGA GAT GGA GGG CGG CAT GGC GGG CAC-3' (FRAG 52) (SEQ. ID NO: 62) WO 00/62736 PCT/USOO/08020 107 5'-GGC GGC CTG GAA AGC TGA GAT GGA GGG CGG CAT GGC GGG CA-3 (FRAG 53) (SEQ. ID NO: 63) 5'-GGC GGC CTG GAA AGC TGA GAT GGA GGG CGG CAT GGC GGG C-3' (FRAG 54) (SEQ. ID NO: 64) 5'-GGC GGC CTG GAA AGC TGA GAT GGA GGG CGG CAT GGC GGG -3' (FRAG 55) (SEQ. ID NO: 65) 5'-GGC GGC CTG GAA AGC TGA GAT GGA GGG CGG CAT GGC GG-3' (FRAG 56) (SEQ. ID NO: 66) 5 5'-GGC GGC CTG GAA AGC TGA GAT GGA GGG CGG CAT GGC G-3'(FRAG 57) (SEQ. ID NO: 67) 5'-GGC GGC CTG GAA AGC TGA GAT GGA GGG CGG CAT GGC -3' (FRAG 58) (SEQ. ID NO: 68) 5'-GGC GGC CTG GAA AGC TGA GAT GGA GGG CGG CAT GG -3' (FRAG 59) (SEQ. ID NO: 69) 5'-GGC GGC CTG GAA AGC TGA GAT GGA GGG CGG CAT G -3' (FRAG 60) (SEQ. ID NO: 70) 5'-GGC GGC CTG GAA AGC TGA GAT GGA GGG CGG CAT -3' (FRAG 61) (SEQ. ID NO: 71) 10 5'-GGC GGC CTG GAA AGC TGA GAT GGA GGG CGG CA-3' (FRAG 62) (SEQ. ID NO: 72) 5'-GGC GGC CTG GAA AGC TGA GAT GGA GGG CGG C-3' (FRAG 63) (SEQ. ID NO: 73) 5'-GGC GGC CTG GAA AGC TGA GAT GGA GGG CGG -3' (FRAG 64) (SEQ. ID NO: 74) 5'-GGC GGC CTG GAA AGC TGA GAT GGA GGG CG -3' (FRAG 65) (SEQ. ID NO: 75) 5'-GGC GGC CTG GAA AGC TGA GAT GGA GGG C -3' (FRAG 66) (SEQ. ID NO: 76) 15 5'-GGC GGC CTG GAA AGC TGA GAT GGA GGG -3' (FRAG 67) (SEQ. ID NO: 77) 5'-GGC GGC CTG GAA AGC TGA GAT GGA GG -3' (FRAG 68) (SEQ. ID NO: 78) 5'-GGC GGC CTG GAA AGC TGA GAT GGA G -3' (FRAG 69) (SEQ. ID NO: 79) 5'-GGC GGC CTG GAA AGC TGA GAT GGA -3' (FRAG 70) (SEQ. ID NO: 80) 5'-GGC GGC CTG GAA AGC TGA GAT GG -3' (FRAG 71) (SEQ. ID NO: 81) 20 5'-GGC GGC CTG GAA AGC TGA GAT G -3' FRAGG 72) (SEQ. ID NO: 82) 5'-GGC GGC CTG GAA AGC TGA GAT -3' (FRAG 73) (SEQ. ID NO: 83) 5'-GGC GGC CTG GAA AGC TGA GA-3' (FRAG 74) (SEQ. ID NO: 84) 5'-GGC GGC CTG GAA AGC TGA G-3' FRAGG 75) (SEQ. ID NO: 85) 5'-GGC GGC CTG GAA AGC TGA-3' (FRAG 76) (SEQ. ID NO: 86) 25 5'-GGC GGC CTG GAA AGC TG-3' FRAGG 77) (SEQ. ID NO: 87) 5'-GGC GGC CTG GAA AGC T-3' FRAGG 78) (SEQ. ID NO: 88) 5'-GGC GGC CTG GAA AGC-3' FRAGG 79) (SEQ. ID NO: 89) 5'-GGC GGC CTG GAA AG-3' (FRAG 80) (SEQ. ID NO: 90) 5'-GGC GGC CTG GAA A-3' (FRAG 81) (SEQ. ID NO: 91) 30 5'-GGC GGC CTG GAA-3' (FRAG 82) (SEQ. ID NO: 92) 5'-GGC GGC CTG GA-3' (FRAG 83) (SEQ. ID NO: 93) 5'-GGC GGC CTG G-3' (FRAG 84) (SEQ. ID NO: 94) 5'-GC GGC CTG GAA AGC TGA GAT GGA GGG CGG CAT GGC GGG CAC AGG CTG GGC-3' FRAGG 85) (SEQ. ID NO: 95) 35 5'-GC GGC CTG GAA AGC TGA GAT GGA GGG CGG CAT GGC GGG CAC AGG CTG GG-3' FRAGG 86) (SEQ. ID NO: 96) 5'-GC GGC CTG GAA AGC TGA GAT GGA GGG CGG CAT GGC GGG CAC AGG CTG G-3' (FRAG 87) (SEQ. ID NO: 97) 5'-GC GGC CTG GAA AGC TGA GAT GGA GGG CGG CAT GGC GGG CAC AGG CTG -3' (FRAG 88) (SEQ. ID NO: 40 98) 5'-GC GGC CTG GAA AGC TGA GAT GGA GGG CGG CAT GGC GGG CAC AGG CT-3' FRAGG 89) (SEQ. ID NO: 99) 5'-GC GGC CTG GAA AGC TGA GAT GGA GGG CGG CAT GGC GGG CAC AGG C-3' (FRAG 90) (SEQ. ID NO: 100) 5'-GC GGC CTG GAA AGC TGA GAT GGA GGG CGG CAT GGC GGG CAC AGG -3' (FRAG 91) (SEQ. ID NO: 101) 45 5'-GC GGC CTG GAA AGC TGA GAT GGA GGG CGG CAT GGC GGG CAC AG-3' (FRAG 92) (SEQ. ID NO: 102) 5'-GC GGC CTG GAA AGC TGA GAT GGA GGG CGG CAT GGC GGG CAC A-3' (FRAG 93) (SEQ. ID NO: 103) 5'-GC GGC CTG GAA AGC TGA GAT GGA GGG CGG CAT GGC GGG CAC-3' (FRAG 94) (SEQ. ID NO: 104) 5'-GC GGC CTG GAA AGC TGA GAT GGA GGG CGG CAT GGC GGG CA-3' FRAGG 95) (SEQ. ID NO: 105) 5'-GC GGC CTG GAA AGC TGA GAT GGA GGG CGG CAT GGC GGG C-3' (FRAG 96) (SEQ. ID NO: 106) 50 5'-GC GGC CTG GAA AGC TGA GAT GGA GGG CGG CAT GGC GGG -3' (FRAG 97) (SEQ. ID NO: 107) 5'-GC GGC CTG GAA AGC TGA GAT GGA GGG CGG CAT GGC GG-3' (FRAG 98) (SEQ. ID NO: 108) 5'-GC GGC CTG GAA AGC TGA GAT GGA GGG CGG CAT GGC G-3' (FRAG 99) (SEQ. ID NO: 109) 5'-GC GGC CTG GAA AGC TGA GAT GGA GGG CGG CAT GGC -3' (FRAG 100) (SEQ. ID NO: 110) 5'-GC GGC CTG GAA AGC TGA GAT GGA GGG CGG CAT GG -3' (FRAG 101) (SEQ. ID NO: 111) 55 5'-GC GGC CTG GAA AGC TGA GAT GGA GGG CGG CAT G -3' (FRAG 102) (SEQ. ID NO: 112) 5'-GC GGC CTG GAA AGC TGA GAT GGA GGG CGG CAT -3' (FRAG 103) (SEQ. ID NO: 113) 5'-GC GGC CTG GAA AGC TGA GAT GGA GGG CGG CA-3' FRAGG 104) (SEQ. ID NO: 114) 5'-GC GGC CTG GAA AGC TGA GAT GGA GGG CGG C-3' (FRAG 105) (SEQ. ID NO: 115) 5'-GC GGC CTG GAA AGC TGA GAT GGA GGG CGG -3' (FRAG 106) (SEQ. ID NO: 116) 60 5'-GC GGC CTG GAA AGC TGA GAT GGA GGG CG -3' (FRAG 107) (SEQ. ID NO: 117) 5'-GC GGC CTG GAA AGC TGA GAT GGA GGG C -3' (FRAG 108) (SEQ. ID NO: 118) 5'-GC GGC CTG GAA AGC TGA GAT GGA GGG -3' (FRAG 109) (SEQ. ID NO: 119) 5'-GC GGC CTG GAA AGC TGA GAT GGA GG -3' (FRAG 110) (SEQ. ID NO: 120) 5'-GC GGC CTG GAA AGC TGA GAT GGA G -3' (FRAG 111) (SEQ. ID NO: 121) 65 5'-GC GGC CTG GAA AGC TGA GAT GGA -3' (FRAG 112) (SEQ. ID NO: 122) 5'-GC GGC CTG GAA AGC TGA GAT GG -3' (FRAG 113) (SEQ. ID NO: 123) WO 00/62736 PCT/USOO/08020 108 5'-GC GGC CTG GAA AGC TGA GAT G -3' (FRAG 114) (SEQ. ID NO: 124) 5'-GC GGC CTG GAA AGC TGA GAT -3' (FRAG 115) (SEQ. ID NO: 125) 5'-GC GGC CTG GAA AGC TGA GA-3' (FRAG 116) (SEQ. ID NO: 126) 5'-GC GGC CTG GAA AGC TGA G-3' (FRAG 117) (SEQ. ID NO: 127) 5 5'-GC GGC CTG GAA AGC TGA-3' (FRAG 118) (SEQ. ID NO: 128) 5'-GC GGC CTG GAA AGC TG-3' (FRAG 119) (SEQ. ID NO: 129) 5'-GC GGC CTG GAA AGC T-3' (FRAG 120) (SEQ. ID NO: 130) 5'-GC GGC CTG GAA AGC-3' (FRAG 121) (SEQ. ID NO: 131) 5'-GC GGC CTG GAA AG-3' (FRAG 122) (SEQ. ID NO: 132) 10 5'-GC GGC CTG GAA A-3' (FRAG 123) (SEQ. ID NO: 133) 5'-GC GGC CTG GAA-3' (FRAG 124) (SEQ. ID NO: 134) 5'-GC GGC CTG GA-3' (FRAG 125) (SEQ. ID NO: 135) 5'-C GGC CTG GAA AGC TGA GAT GGA GGG CGG CAT GGC GGG CAC AGG CTG GGC-3' (FRAG 126) (SEQ. ID NO: 136) 15 5'-C GGC CTG GAA AGC TGA GAT GGA GGG CGG CAT GGC GGG CAC AGG CTG GG-3' (FRAG 127) (SEQ. ID NO: 137) 5'-C GGC CTG GAA AGC TGA GAT GGA GGG CGG CAT GGC GGG CAC AGG CTG G-3' (FRAG 128) (SEQ. ID NO: 138) 5'-C GGC CTG GAA AGC TGA GAT GGA GGG CGG CAT GGC GGG CAC AGG CTG -3' (FRAG 129) (SEQ. ID NO: 20 139) 5'-C GGC CTG GAA AGC TGA GAT GGA GGG CGG CAT GGC GGG CAC AGG CT-3' (FRAG 130) (SEQ. ID NO: 140) 5'-C GGC CTG GAA AGC TGA GAT GGA GGG CGG CAT GGC GGG CAC AGG C-3' (FRAG 131) (SEQ. ID NO: 141) 5'-C GGC CTG GAA AGC TGA GAT GGA GGG CGG CAT GGC GGG CAC AGG -3' (FRAG 132) (SEQ. ID NO: 142) 5'-C GGC CTG GAA AGC TGA GAT GGA GGG CGG CAT GGC GGG CAC AG-3' (FRAG 133) (SEQ. ID NO: 143) 25 5'-C GGC CTG GAA AGC TGA GAT GGA GGG CGG CAT GGC GGG CAC A-3' (FRAG 134) (SEQ. ID NO: 144) 5'-C GGC CTG GAA AGC TGA GAT GGA GGG CGG CAT GGC GGG CAC-3' (FRAG 135) (SEQ. ID NO: 145) 5'-C GGC CTG GAA AGC TGA GAT GGA GGG CGG CAT GGC GGG CA-3' (FRAG 136) (SEQ. ID NO: 146) 5'-C GGC CTG GAA AGC TGA GAT GGA GGG CGG CAT GGC GGG C-3' (FRAG 137) (SEQ. ID NO: 147) 5'-C GGC CTG GAA AGC TGA GAT GGA GGG CGG CAT GGC GGG -3' (FRAG 138) (SEQ. ID NO: 148) 30 5'-C GGC CTG GAA AGC TGA GAT GGA GGG CGG CAT GGC GG-3' FRAGG 139) (SEQ. ID NO: 149) 5'-C GGC CTG GAA AGC TGA GAT GGA GGG CGG CAT GGC G-3' (FRAG 140) (SEQ. ID NO: 150) 5'-C GGC CTG GAA AGC TGA GAT GGA GGG CGG CAT GGC -3' (FRAG 141) (SEQ. ID NO: 151) 5'-C GGC CTG GAA AGC TGA GAT GGA GGG CGG CAT GG -3' (FRAG 142) (SEQ. ID NO: 152) 5'-C GGC CTG GAA AGC TGA GAT GGA GGG CGG CAT G -3' (FRA 143) (SEQ. ID NO: 153) 35 5'-C GGC CTG GAA AGC TGA GAT GGA GGG CGG CAT -3' (FRAG 144) (SEQ. ID NO: 154) 5'-C GGC CTG GAA AGC TGA GAT GGA GGG CGG CA-3' (FRAG 145) (SEQ. ID NO: 155) 5'-C GGC CTG GAA AGC TGA GAT GGA GGG CGG C-3' (FRAG 146) (SEQ. ID NO: 156) 5'-C GGC CTG GAA AGC TGA GAT GGA GGG CGG -3' (FRAG 147) (SEQ. ID NO: 157) 5'-C GGC CTG GAA AGC TGA GAT GGA GGG CG -3' (FRAG 148) (SEQ. ID NO: 158) 40 5'-C GGC CTG GAA AGC TGA GAT GGA GGG C -3' (FRAG 148) (SEQ. ID NO: 159) 5'-C GGC CTG GAA AGC TGA GAT GGA GGG -3' (FRAG 150) (SEQ. ID NO: 160) 5'-C GGC CTG GAA AGC TGA GAT GGA GG -3' (FRAG 151) (SEQ. ID NO: 161) 5'-C GGC CTG GAA AGC TGA GAT GGA G -3' (FRAG 152) (SEQ. ID NO: 162) 5'-C GGC CTG GAA AGC TGA GAT GGA -3' (FRAG 153) (SEQ. ID NO: 163) 45 5'-C GGC CTG GAA AGC TGA GAT GG -3' (FRAG 154) (SEQ. ID NO: 164) 5'-C GGC CTG GAA AGC TGA GAT G -3' (FRAG 155) (SEQ. ID NO: 165) 5'-C GGC CTG GAA AGC TGA GAT -3' (FRAG 156) (SEQ. ID NO: 166) 5'-C GGC CTG GAA AGC TGA GA-3' (FRAG 157) (SEQ. ID NO: 167) 5'-C GGC CTG GAA AGC TGA G-3' (FRAG 158) (SEQ. ID NO: 168) 50 5'-C GGC CTG GAA AGC TGA-3' (FRAG 159) (SEQ. ID NO: 169) 5'-C GGC CTG GAA AGC TG-3' (FRAG 160) (SEQ. ID NO: 170) 5'-C GGC CTG GAA AGC T-3' (FRAG 161) (SEQ. ID NO: 171) 5'-C GGC CTG GAA AGC-3' (FRAG 162) (SEQ. ID NO: 172) 5'-C GGC CTG GAA AG-3' (FRAG 163) (SEQ. ID NO: 173) 55 5'-C GGC CTG GAA A-3' (FRAG 164) (SEQ. ID NO: 174) 5'-C GGC CTG GAA-3' (FRAG 165) (SEQ. ID NO: 175) 5'- GGC CTG GAA AGC TGA GAT GGA GGG CGG CAT GGC GGG CAC AGG CTG GGC-3' FRAGG 166) (SEQ. ID NO: 176) 5'- GGC CTG GAA AGC TGA GAT GGA GGG CGG CAT GGC GGG CAC AGG CTG GG-3' (FRAG 167) (SEQ. ID NO: 60 177) 5'- GGC CTG GAA AGC TGA GAT GGA GGG CGG CAT GGC GGG CAC AGG CTG G-3' FRAGG 168) (SEQ. ID NO: 178) 5'- GGC CTG GAA AGC TGA GAT GGA GGG CGG CAT GGC GGG CAC AGG CTG -3' (FRAG 169) (SEQ. ID NO: 179) 65 5'- GGC CTG GAA AGC TGA GAT GGA GGG CGG CAT GGC GGG CAC AGG CT-3' (FRAG 170) (SEQ. ID NO: 180) 5'- GGC CTG GAA AGC TGA GAT GGA GGG CGG CAT GGC GGG CAC AGG C-3' (FRAG 171) (SEQ. ID NO: 181) WO 00/62736 PCT/USOO/08020 109 5'- GGC CTG GAA AGC TGA GAT GGA GGG CGG CAT GGC GGG CAC AGG -3' (FRAG 172) (SEQ. ID NO: 182) 5'- GGC CTG GAA AGC TGA GAT GGA GGG CGG CAT GGC GGG CAC AG-3' (FRAG 173) (SEQ. ID NO: 183) 5'- GGC CTG GAA AGC TGA GAT GGA GGG CGG CAT GGC GGG CAC A-3' (FRAG 174) (SEQ. ID NO: 184) 5'- GGC CTG GAA AGC TGA GAT GGA GGG CGG CAT GGC GGG CAC-3' (FRAG 175) (SEQ. ID NO: 185) 5 5'- GGC CTG GAA AGC TGA GAT GGA GGG CGG CAT GGC GGG CA-3' (FRAG 176) (SEQ. ID NO: 186) 5'- GGC CTG GAA AGC TGA GAT GGA GGG CGG CAT GGC GGG C-3' (FRAG 177) (SEQ. ID NO: 187) 5'- GGC CTG GAA AGC TGA GAT GGA GGG CGG CAT GGC GGG -3' (FRAG 178) (SEQ. ID NO: 188) 5'- GGC CTG GAA AGC TGA GAT GGA GGG CGG CAT GGC GG-3' (FRAG 179) (SEQ. ID NO: 189) 5'- GGC CTG GAA AGC TGA GAT GGA GGG CGG CAT GGC G-3' (FRAG 180) (SEQ. ID NO: 190) 10 5'- GGC CTG GAA AGC TGA GAT GGA GGG CGG CAT GGC -3' (FRAG 181) (SEQ. ID NO: 191) 5'- GGC CTG GAA AGC TGA GAT GGA GGG CGG CAT GG -3' (FRAG 182) (SEQ. ID NO: 192) 5'- GGC CTG GAA AGC TGA GAT GGA GGG CGG CAT G -3' (FRAG 183) (SEQ. ID NO: 193) 5'- GGC CTG GAA AGC TGA GAT GGA GGG CGG CAT -3' (FRAG 184) (SEQ. ID NO: 194) 5'- GGC CTG GAA AGC TGA GAT GGA GGG CGG CA-3' (FRAG 185) (SEQ. ID NO: 195) 15 5'- GGC CTG GAA AGC TGA GAT GGA GGG CGG C-3' (FRAG 186) (SEQ. ID NO: 196) 5'- GGC CTG GAA AGC TGA GAT GGA GGG CGG -3' (FRAG 187) (SEQ. ID NO: 197) 5'- GGC CTG GAA AGC TGA GAT GGA GGG CG -3' (FRAG 188) (SEQ. ID NO: 198) 5'- GGC CTG GAA AGC TGA GAT GGA GGG C -3' (FRAG 189) (SEQ. ID NO: 199) 5'- GGC CTG GAA AGC TGA GAT GGA GGG -3' (FRAG 190) (SEQ. ID NO: 200) 20 5'- GGC CTG GAA AGC TGA GAT GGA GG -3' (FRAG 191) (SEQ. ID NO: 201) 5'- GGC CTG GAA AGC TGA GAT GGA G -3' FRAGG 192) (SEQ. ID NO: 202) 5'- GGC CTG GAA AGC TGA GAT GGA -3' (FRAG 193) (SEQ. ID NO: 203) 5'- GGC CTG GAA AGC TGA GAT GG -3' (FRAG 194) (SEQ. ID NO: 204) 5'- GGC CTG GAA AGC TGA GAT G -3' FRAGG 195) (SEQ. ID NO: 205) 25 5'- GGC CTG GAA AGC TGA GAT -3' FRAGG 196) (SEQ. ID NO: 206) 5'- GGC CTG GAA AGC TGA GA-3' (FRAG 197) (SEQ. ID NO: 207) 5'- GGC CTG GAA AGC TGA G-3' (FRAG 198) (SEQ. ID NO: 208) 5'- GGC CTG GAA AGC TGA-3' (FRAG 199) (SEQ. ID NO: 209) 5'- GGC CTG GAA AGC TG-3' FRAGG 200 (SEQ. ID NO: 210) 30 5'- GGC CTG GAA AGC T-3' (FRAG 201) (SEQ. ID NO: 211) 5'- GGC CTG GAA AGC-3' (FRAG 202) (SEQ. ID NO: 212) 5'- GGC CTG GAA AG-3' (FRAG 203) (SEQ. ID NO: 213) 5'- GGC CTG GAA A-3' (FRAG 204) (SEQ. ID NO: 214) 5'- GC CTG GAA AGC TGA GAT GGA GGG CGG CAT GGC GGG CAC AGG CTG GGC-3' (FRAG 205) (SEQ. ID 35 NO: 215) 5'- GC CTG GAA AGC TGA GAT GGA GGG CGG CAT GGC GGG CAC AGG CTG GG-3' (FRAG 206) (SEQ. ID NO: 216) 5'- GC CTG GAA AGC TGA GAT GGA GGG CGG CAT GGC GGG CAC AGG CTG G-3' (FRAG 207) (SEQ. ID NO: 217) 40 5'- GC CTG GAA AGC TGA GAT GGA GGG CGG CAT GGC GGG CAC AGG CTG -3' (FRAG 208) (SEQ. ID NO: 218) 5'- GC CTG GAA AGC TGA GAT GGA GGG CGG CAT GGC GGG CAC AGG CT-3' (FRAG 209) (SEQ. ID NO: 219) 5'- GC CTG GAA AGC TGA GAT GGA GGG CGG CAT GGC GGG CAC AGG C-3' (FRAG 210) (SEQ. ID NO: 220) 5'- GC CTG GAA AGC TGA GAT GGA GGG CGG CAT GGC GGG CAC AGG -3' (FRAG 211) (SEQ. ID NO: 221) 45 5'- GC CTG GAA AGC TGA GAT GGA GGG CGG CAT GGC GGG CAC AG-3' (FRAG 212) (SEQ. ID NO: 222) 5'- GC CTG GAA AGC TGA GAT GGA GGG CGG CAT GGC GGG CAC A-3' (FRAG 213) (SEQ. ID NO: 223) 5'- GC CTG GAA AGC TGA GAT GGA GGG CGG CAT GGC GGG CAC-3' (FRAG 214) (SEQ. ID NO: 224) 5'- GC CTG GAA AGC TGA GAT GGA GGG CGG CAT GGC GGG CA-3' (FRAG 215) (SEQ. ID NO: 225) 5'- GC CTG GAA AGC TGA GAT GGA GGG CGG CAT GGC GGG C-3' (FRAG 216) (SEQ. ID NO: 226) 50 5'- GC CTG GAA AGC TGA GAT GGA GGG CGG CAT GGC GGG -3' (FRAG 217) (SEQ. ID NO: 227) 5'- GC CTG GAA AGC TGA GAT GGA GGG CGG CAT GGC GG-3' (FRAG 218) (SEQ. ID NO: 228) 5'- GC CTG GAA AGC TGA GAT GGA GGG CGG CAT GGC G-3' (FRAG 219) (SEQ. ID NO: 229) 5'- GC CTG GAA AGC TGA GAT GGA GGG CGG CAT GGC -3' (FRAG 220) (SEQ. ID NO: 230) 5'- GC CTG GAA AGC TGA GAT GGA GGG CGG CAT GG -3' FRAGG 221) (SEQ. ID NO: 231) 55 5'- GC CTG GAA AGC TGA GAT GGA GGG CGG CAT G -3' (FRAG 222) (SEQ. ID NO: 232) 5'- GC CTG GAA AGC TGA GAT GGA GGG CGG CAT -3' (FRAG 223) (SEQ. ID NO: 233) 5'- GC CTG GAA AGC TGA GAT GGA GGG CGG CA-3' (FRAG 224) (SEQ. ID NO: 234) 5'- GC CTG GAA AGC TGA GAT GGA GGG CGG C-3' (FRAG 225) (SEQ. ID NO: 235) 5'- GC CTG GAA AGC TGA GAT GGA GGG CGG -3' (FRAG 226) (SEQ. ID NO: 236) 60 5'- GC CTG GAA AGC TGA GAT GGA GGG CG -3' (FRAG 227) (SEQ. ID NO: 237) 5'- GC CTG GAA AGC TGA GAT GGA GGG C -3' (FRAG 228) (SEQ. ID NO: 238) 5'- GC CTG GAA AGC TGA GAT GGA GGG -3' (FRAG 229) (SEQ. ID NO: 239) 5'- GC CTG GAA AGC TGA GAT GGA GG -3' (FRAG 230) (SEQ. ID NO: 240) 5'- GC CTG GAA AGC TGA GAT GGA G -3' (FRAG 231) (SEQ. ID NO: 241) 65 5'- GC CTG GAA AGC TGA GAT GGA -3' (FRAG 232) (SEQ. ID NO: 242) 5'- GC CTG GAA AGC TGA GAT GG -3' (FRAG 233) (SEQ. ID NO: 243) WO 00/62736 PCT/US00/08020 110 5'- GC CTG GAA AGC TGA GAT G -3' (FRAG 234) (SEQ. ID NO: 244) 5'- GC CTG GAA AGC TGA GAT -3' (FRAG 235) (SEQ. ID NO: 245) 5'- GC CTG GAA AGC TGA GA-3' (FRAG 236) (SEQ. ID NO: 246) 5'- GC CTG GAA AGC TGA G-3' (FRAG 237) (SEQ. ID NO: 247) 5 5'- GC CTG GAA AGC TGA-3' (FRAG 238) (SEQ. ID NO: 248) 5'- GC CTG GAA AGC TG-3' (FRAG 239) (SEQ. ID NO: 249) 5'- GC CTG GAA AGC T-3' (FRAG 240) (SEQ. ID NO: 250) 5'- GC CTG GAA AGC-3' (FRAG 241) (SEQ. ID NO: 251) 5'- GC CTG GAA AG-3' (FRAG 242) (SEQ. ID NO: 252) 10 5'- C CTG GAA AGC TGA GAT GG A GGG CGG CAT GGC GGG CAC AGG CTG GGC-3' (FRAG 243) (SEQ. ID NO: 253) 5'- C CTG GAA AGC TGA GAT GGA GGG CGG CAT GGC GGG CAC AGG CTG GG-3' (FRAG 244) (SEQ. ID NO: 254) 5'- C CTG GAA AGC TGA GAT GGA GGG CGG CAT GGC GGG CAC AGG CTG G-3' (FRAG 245) (SEQ. ID NO: 15 255) 5'- C CTG GAA AGC TGA GAT GGA GGG CGG CAT GGC GGG CAC AGG CTG -3' (FRAG 246) (SEQ. ID NO: 256) 5'- C CTG GAA AGC TGA GAT GGA GGG CGG CAT GGC GGG CAC AGG CT-3' (FRAG 247) (SEQ. ID NO: 257) 5'- C CTG GAA AGC TGA GAT GGA GGG CGG CAT GGC GGG CAC AGG C-3' (FRAG 248) (SEQ. ID NO: 258) 5'- C CTG GAA AGC TGA GAT GGA GGG CGG CAT GGC GGG CAC AGG -3' FRAGG 249) (SEQ. ID NO: 259) 20 5'- C CTG GAA AGC TGA GAT GGA GGG CGG CAT GGC GGG CAC AG-3' (FRAG 250) (SEQ. ID NO: 260) 5'- C CTG GAA AGC TGA GAT GGA GGG CGG CAT GGC GGG CAC A-3' (FRAG 251) (SEQ. ID NO: 261) 5'- C CTG GAA AGC TGA GAT GGA GGG CGG CAT GGC GGG CAC-3' (FRAG 252) (SEQ. ID NO: 262) 5'- C CTG GAA AGC TGA GAT GGA GGG CGG CAT GGC GGG CA-3' (FRAG 253) (SEQ. ID NO: 263) 5'- C CTG GAA AGC TGA GAT GGA GGG CGG CAT GGC GGG C-3' (FRAG 254) (SEQ. ID NO: 264) 25 5'- C CTG GAA AGC TGA GAT GGA GGG CGG CAT GGC GGG -3' (FRAG 255) (SEQ. ID NO: 265) 5'- C CTG GAA AGC TGA GAT GGA GGG CGG CAT GGC GG-3' (FRAG 256) (SEQ. ID NO: 266) 5'- C CTG GAA AGC TGA GAT GGA GGG CGG CAT GGC G-3' (FRAG 257) (SEQ. ID NO: 267) 5'- C CTG GAA AGC TGA GAT GGA GGG CGG CAT GGC -3' FRAGG 258) (SEQ. ID NO: 268) 5'- C CTG GAA AGC TGA GAT GGA GGG CGG CAT GG -3' (FRAG 259) (SEQ. ID NO: 269) 30 5'- C CTG GAA AGC TGA GAT GGA GGG CGG CAT G -3' (FRAG 260) (SEQ. ID NO: 270) 5'- C CTG GAA AGC TGA GAT GGA GGG CGG CAT -3' (FRAG 261) (SEQ. ID NO: 271) 5'- C CTG GAA AGC TGA GAT GGA GGG CGG CA-3' (FRAG 262) (SEQ. ID NO: 272) 5'- C CTG GAA AGC TGA GAT GGA GGG CGG C-3' FRAGG 263) (SEQ. ID NO: 273) 5'- C CTG GAA AGC TGA GAT GGA GGG CGG -3' (FRAG 264) (SEQ. ID NO: 274) 35 5'- C CTG GAA AGC TGA GAT GGA GGG CG -3' (FRAG 265) (SEQ. ID NO: 275) 5'- C CTG GAA AGC TGA GAT GGA GGG C -3' (FRAG 266) (SEQ. ID NO: 276) 5'- C CTG GAA AGC TGA GAT GGA GGG -3' FRAGG 267) (SEQ. ID NO: 277) 5'- C CTG GAA AGC TGA GAT GGA GG -3' (FRAG 268) (SEQ. ID NO: 278) 5'- C CTG GAA AGC TGA GAT GGA G -3' (FRAG 269) (SEQ. ID NO: 279) 40 5'- C CTG GAA AGC TGA GAT GGA -3' (FRAG 270) (SEQ. ID NO: 280) 5'- C CTG GAA AGC TGA GAT GG -3' (FRAG 271) (SEQ. ID NO: 281) 5'- C CTG GAA AGC TGA GAT G -3' (FRAG 272) (SEQ. ID NO: 282) 5'- C CTG GAA AGC TGA GAT -3' (FRAG 273) (SEQ. ID NO: 283) 5'- C CTG GAA AGC TGA GA-3' (FRAG 274) (SEQ. ID NO: 284) 45 5'- C CTG GAA AGC TGA G-3' (FRAG 275) (SEQ. ID NO: 285) 5'- C CTG GAA AGC TGA-3' (FRAG 276) (SEQ. ID NO: 286) 5'- C CTG GAA AGC TG-3' (FRAG 277) (SEQ. ID NO: 287) 5'- C CTG GAA AGC T-3' (FRAG 278) (SEQ. ID NO: 288) 5'- C CTG GAA AGC-3' (FRAG 279) (SEQ. ID NO: 289) 50 5'- CTG GAA AGC TGA GAT GGA GGG CGG CAT GGC GGG CAC AGG CTG GGC-3' (FRAG 280) (SEQ. ID NO: 290) 5'- CTG GAA AGC TGA GAT GGA GGG CGG CAT GGC GGG CAC AGG CTG GG-3' (FRAG 281) (SEQ. ID NO: 291) 5'- CTG GAA AGC TGA GAT GGA GGG CGG CAT GGC GGG CAC AGG CTG G-3' (FRAG 282) (SEQ. ID NO: 292) 55 5'- CTG GAA AGC TGA GAT GGA GGG CGG CAT GGC GGG CAC AGG CTG -3' FRAGG 283) (SEQ. ID NO: 293) 5'- CTG GAA AGC TGA GAT GGA GGG CGG CAT GGC GGG CAC AGG CT-3' (FRAG 284) (SEQ. ID NO: 294) 5'- CTG GAA AGC TGA GAT GGA GGG CGG CAT GGC GGG CAC AGG C-3' (FRAG 285) (SEQ. ID NO: 295) 5'- CTG GAA AGC TGA GAT GGA GGG CGG CAT GGC GGG CAC AGG -3' (FRAG 286) (SEQ. ID NO: 296) 5'- CTG GAA AGC TGA GAT GGA GGG CGG CAT GGC GGG CAC AG-3' (FRAG 287) (SEQ. ID NO: 297) 60 5'- CTG GAA AGC TGA GAT GGA GGG CGG CAT GGC GGG CAC A-3' (FRAG 288) (SEQ. ID NO: 298) 5'- CTG GAA AGC TGA GAT GGA GGG CGG CAT GGC GGG CAC-3' FRAGG 289) (SEQ. ID NO: 299) 5'- CTG GAA AGC TGA GAT GGA GGG CGG CAT GGC GGG CA-3' (FRAG 290) (SEQ. ID NO: 300) 5'- CTG GAA AGC TGA GAT GGA GGG CGG CAT GGC GGG C-3' FRAGG 291) (SEQ. ID NO: 301) 5'- CTG GAA AGC TGA GAT GGA GGG CGG CAT GGC GGG -3' (FRAG 292) (SEQ. ID NO: 302) 65 5'- CTG GAA AGC TGA GAT GGA GGG CGG CAT GGC GG-3' (FRAG 293) (SEQ. ID NO: 303) 5'- CTG GAA AGC TGA GAT GGA GGG CGG CAT GGC G-3' (FRAG 294) (SEQ. ID NO: 304) WO 00/62736 PCT/US00/08020 111 5'- CTG GAA AGC TGA GAT GGA GGG CGG CAT GGC -3' (FRAG 295) (SEQ. ID NO: 305) 5'- CTG GAA AGC TGA GAT GGA GGG CGG CAT G -3' (FRAG 296) (SEQ. ID NO: 306) 5'- CTG GAA AGC TGA GAT GGA GGG CGG CAT G -3' (FRAG 297) (SEQ. ID NO: 307) 5'- CTG GAA AGC TGA GAT GGA GGG CGG CAT -3' (FRAG 298) (SEQ. ID NO: 308) 5 5'- CTG GAA AGC TGA GAT GGA GGG CGG CA-3' (FRAG 299) (SEQ. ID NO: 309) 5'- CTG GAA AGC TGA GAT GGA GGG CGG C-3' (FRAG 300) (SEQ. ID NO: 310) 5'- CTG GAA AGC TGA GAT GGA GGG CG -3' (FRAG 301) (SEQ. ID NO: 311) 5'- CTG GAA AGC TGA GAT GGA GGG CG -3' (FRAG 302) (SEQ. ID NO: 312) 5'- CTG GAA AGC TGA GAT GGA GGG C -3' (FRAG 303) (SEQ. ID NO: 313) 10 5'- CTG GAA AGC TGA GAT GGA GG -3' (FRAG 304) (SEQ. ID NO: 314) 5'- CTG GAA AGC TGA GAT GGA GG -3' (FRAG 305) (SEQ. ID NO: 315) 5'- CTG GAA AGC TGA GAT GGA G -3' (FRAG 306) (SEQ. ID NO: 316) 5'- CTG GAA AGC TGA GAT GGA -3' (FRAG 307) (SEQ. ID NO: 317) 5'- CTG GAA AGC TGA GAT G -3' FRAGG 308) (SEQ. ID NO: 318) 15 5'- CTG GAA AGC TGA GAT 0 -3' (FRAG 309) (SEQ. ID NO: 319) 5'- CTG GAA AGC TGA GAT -3' (FRAG 310) (SEQ. ID NO: 320) 5'- CTG GAA AGC TGA GA-3' (FRAG 311) (SEQ. ID NO: 321) 5'- CTG GAA AGC TGA 0-3' (FRAG 312) (SEQ. ID NO: 322) 5'- CTG GAA AGC TGA-3' (FRAG 313) (SEQ. ID NO: 323) 20 5'- CTG GAA AGC TG-3' (FRAG 314) (SEQ. ID NO: 324) 5'- CTG GAA AGC T-3' (FRAG 315) (SEQ. ID NO: 325) 5'- TG GAA AGC TGA GAT GGA GGG CGG CAT GGC GGG CAC AGG CTG GGC-3' (FRAG 316) (SEQ. ID NO: 326) 5'- TG GAA AGC TGA GAT GGA GGG CGG CAT GGC GGG CAC AGG CTG GG-3' (FRAG 317) (SEQ. ID NO: 327) 25 5'- TG GAA AGC TGA GAT GGA GGG CGG CAT GGC GGG CAC AGG CTG G-3' (FRAG 318) (SEQ. ID NO: 328) 5'- TG GAA AGC TGA GAT GGA GGG CGG CAT GGC GGG CAC AGG CTG -3' (FRAG 319) (SEQ. ID NO: 329) 5'- TG GAA AGC TGA GAT GGA GGG CGG CAT GGC GGG CAC AGG CT-3' (FRAG 320) (SEQ. ID NO: 330) 5'- TG GAA AGC TGA GAT GGA GGG CGG CAT GGC GGG CAC AGG C-3' (FRAG 321) (SEQ. ID NO: 331) 5'- TG GAA AGC TGA GAT GGA GGG CGG CAT GGC GGG CAC AGG -3' (FRAG 322) (SEQ. ID NO: 332) 30 5'- TG GAA AGC TGA GAT GGA GGG CGG CAT GGC GGG CAC AG-3' (FRAG 323) (SEQ. ID NO: 333) 5'- TG GAA AGC TGA GAT GGA GGG CGG CAT GGC GGG CAC A-3' (FRAG 324) (SEQ. ID NO: 334) 5'- TG GAA AGC TGA GAT GGA GGG CGG CAT GGC GGG CAC-3' FRAGG 325) (SEQ. ID NO: 335) 5'- TG GAA AGC TGA GAT GGA GGG CGG CAT GGC GGG CA-3' (FRAG 326) (SEQ. ID NO: 336) 5'- TG GAA AGC TGA GAT GGA GGG CGG CAT GGC GGG C-3' (FRAG 327) (SEQ. ID NO: 337) 35 5'- TG GAA AGC TGA GAT GGA GGG CGG CAT GGC GGG -3' (FRAG 328) (SEQ. ID NO: 338) 5'- TG GAA AGC TGA GAT GGA GGG CGG CAT GGC GG-3' (FRAG 329) (SEQ. ID NO: 339) 5'- TG GAA AGC TGA GAT GGA GGG CGG CAT GGC G-3' (FRAG 330) (SEQ. ID NO: 340) 5'- TG GAA AGC TGA GAT GGA GGG CGG CAT GGC -3' (FRAG 331) (SEQ. ID NO: 341) 5'- TG GAA AGC TGA GAT GGA GGG CGG CAT GG -3' (FRAG 332) (SEQ. ID NO: 342) 40 5'- TG GAA AGC TGA GAT GGA GGG CGG CAT G -3' (FRAG 333) (SEQ. ID NO: 343) 5'- TG GAA AGC TGA GAT GGA GGG CGG CAT -3' (FRAG 334) (SEQ. ID NO: 344) 5'- TG GAA AGC TGA GAT GGA GGG CGG CA-3' (FRAG 335) (SEQ. ID NO: 345) 5'- TG GAA AGC TGA GAT GGA GGG CGG C-3' (FRAG 336) (SEQ. ID NO: 346) 5'- TG GAA AGC TGA GAT GGA GGG CGG -3' (FRAG 337) (SEQ. ID NO: 347) 45 5'- TG GAA AGC TGA GAT GGA GGG CG -3' (FRAG 338) (SEQ. ID NO: 348) 5'- TG GAA AGC TGA GAT GGA GGG C -3' (FRAG 339) (SEQ. ID NO: 349) 5'- TG GAA AGC TGA GAT GGA GGG -3' (FRAG 340) (SEQ. ID NO: 350) 5'- TG GAA AGC TGA GAT GGA GG -3' (FRAG 341) (SEQ. ID NO: 351) 5'- TG GAA AGC TGA GAT GGA G -3' FRAGG 342) (SEQ. ID NO: 352) 50 5'- TG GAA AGC TGA GAT GGA -3' (FRAG 343) (SEQ. ID NO: 353) 5'- TG GAA AGC TGA GAT GG -3' (FRAG 344) (SEQ. ID NO: 354) 5'- TG GAA AGC TGA GAT G -3' (FRAG 345) (SEQ. ID NO: 355) 5'- TG GAA AGC TGA GAT -3' (FRAG 346) (SEQ. ID NO: 356) 5'- TG GAA AGC TGA GA-3' (FRAG 347) (SEQ. ID NO: 357) 55 5'- TG GAA AGC TGA G-3' (FRAG 348) (SEQ. ID NO: 358) 5'- TG GAA AGC TGA-3' (FRAG 349) (SEQ. ID NO: 359) 5'- TG GAA AGC TG-3' (FRAG 350) (SEQ. ID NO: 360) 5'- G GAA AGC TGA GAT GGA GGG CGG CAT GGC GGG CAC AGG CTG GGC-3' (FRAG 351) (SEQ. ID NO: 361) 5'- G GAA AGC TGA GAT GGA GGG CGG CAT GGC GGG CAC AGG CTG GG-3' (FRAG 352) (SEQ. ID NO: 362) 60 5'- G GAA AGC TGA GAT GGA GGG CGG CAT GGC GGG CAC AGG CTG G-3' (FRAG 353) (SEQ. ID NO: 363) 5'- G GAA AGC TGA GAT GGA GGG CGG CAT GGC GGG CAC AGG CTG -3' (FRAG 354) (SEQ. ID NO: 364) 5'- G GAA AGC TGA GAT GGA GGG CGG CAT GGC GGG CAC AGG CT-3' (FRAG 355) (SEQ. ID NO: 365) 5'- G GAA AGC TGA GAT GGA GGG CGG CAT GGC GGG CAC AGG C-3' (FRAG 356) (SEQ. ID NO: 366) 5'- G GAA AGC TGA GAT GGA GGG CGG CAT GGC GGG CAC AGG -3' (FRAG 357) (SEQ. ID NO: 367) 65 5'- G GAA AGC TGA GAT GGA GGG CGG CAT GGC GGG CAC AG-3' (FRAG 358) (SEQ. ID NO: 368) 5'- G GAA AGC TGA GAT GGA GGG CGG CAT GGC GGG CAC A-3' (FRAG 359) (SEQ. ID NO: 369) WO 00/62736 PCT/US00/08020 112 5'- G GAA AGC TGA GAT GGA GGG CGG CAT GGC GGG CAC-3' (FRAG 360) (SEQ. ID NO: 370) 5'- G GAA AGC TGA GAT GGA GGG CGG CAT GGC GGG CA-3' (FRAG 361) (SEQ. ID NO: 371) 5'- G GAA AGC TGA GAT GGA GGG CGG CAT GGC GGG C-3' (FRAG 362) (SEQ. ID NO: 372) 5'- G GAA AGC TGA GAT GGA GGG CGG CAT GGC GGG -3' (FRAG 363) (SEQ. ID NO: 373) 5 5'- G GAA AGC TGA GAT GGA GGG CGG CAT GGC GG-3' (FRAG 364) (SEQ. ID NO: 374) 5'- G GAA AGC TGA GAT GGA GGG CGG CAT GGC G-3' (FRAG 365) (SEQ. ID NO: 375) 5'- G GAA AGC TGA GAT GGA GGG CGG CAT GGC -3' (FRAG 366) (SEQ. ID NO: 376) 5'- G GAA AGC TGA GAT GGA GGG CGG CAT GG -3' (FRAG 367) (SEQ. ID NO: 377) 5'- G GAA AGC TGA GAT GGA GGG CGG CAT G -3' (FRAG 368) (SEQ. ID NO: 378) 10 5'- G GAA AGC TGA GAT GGA GGG CGG CAT -3' FRAGG 369) (SEQ. ID NO: 379) 5'- G GAA AGC TGA GAT GGA GGG CGG CA-3' (FRAG 370) (SEQ. ID NO: 380) 5'- G GAA AGC TGA GAT GGA GGG CGG C-3' (FRAG 371) (SEQ. ID NO: 381) 5'- G GAA AGC TGA GAT GGA GGG CGG -3' (FRAG 372) (SEQ. ID NO: 382) 5'- G GAA AGC TGA GAT GGA GGG CG -3' (FRAG 373) (SEQ. ID NO: 383) 15 5'- G GAA AGC TGA GAT GGA GGG C -3' (FRAG 374) (SEQ. ID NO: 384) 5'- G GAA AGC TGA GAT GGA GGG -3' (FRAG 375) (SEQ. ID NO: 385) 5'- G GAA AGC TGA GAT GGA GG -3' (FRAG 376) (SEQ. ID NO: 386) 5'- G GAA AGC TGA GAT GGA G -3' (FRAG 377) (SEQ. ID NO: 387) 5'- G GAA AGC TGA GAT GGA -3' (FRAG 378) (SEQ. ID NO: 388) 20 5'- G GAA AGC TGA GAT GG -3' (FRAG 379) (SEQ. ID NO: 389) 5'- G GAA AGC TGA GAT G -3' (FRAG 380) (SEQ. ID NO: 390) 5'- G GAA AGC TGA GAT -3' (FRAG 381) (SEQ. ID NO: 391) 5'- G GAA AGC TGA GA-3' (FRAG 382) (SEQ. ID NO: 392) 5'- G GAA AGC TGA G-3' (FRAG 383) (SEQ. ID NO: 393) 25 5'- G GAA AGC TGA-3' (FRAG 384) (SEQ. ID NO: 394) 5'- GAA AGC TGA GAT GGA GGG CGG CAT GGC GGG CAC AGG CTG GGC-3' (FRAG 385) (SEQ. ID NO: 395) 5'- GAA AGC TGA GAT GGA GGG CGG CAT GGC GGG CAC AGG CTG GG-3' (FRAG 386) (SEQ. ID NO: 396) 5'- GAA AGC TGA GAT GGA GGG CGG CAT GGC GGG CAC AGG CTG G-3' (FRAG 387) (SEQ. ID NO: 397) 5'- GAA AGC TGA GAT GGA GGG CGG CAT GGC GGG CAC AGG CTG -3' (FRAG 388) (SEQ. ID NO: 398) 30 5'- GAA AGC TGA GAT GGA GGG CGG CAT GGC GGG CAC AGG CT-3' (FRAG 389) (SEQ. ID NO: 399) 5'- GAA AGC TGA GAT GGA GGG CGG CAT GGC GGG CAC AGG C-3' (FRAG 390) (SEQ. ID NO: 400) 5'- GAA AGC TGA GAT GGA GGG CGG CAT GGC GGG CAC AGG -3' (FRAG 391) (SEQ. ID NO: 401) 5'- GAA AGC TGA GAT GGA GGG CGG CAT GGC GGG CAC AG-3' (FRAG 392) (SEQ. ID NO: 402) 5'- GAA AGC TGA GAT GGA GGG CGG CAT GGC GGG CAC A-3' (FRAG 393) (SEQ. ID NO: 403) 35 5'- GAA AGC TGA GAT GGA GGG CGG CAT GGC GGG CAC-3' (FRAG 394) (SEQ. ID NO: 404) 5'- GAA AGC TGA GAT GGA GGG CGG CAT GGC GGG CA-3' (FRAG 395) (SEQ. ID NO: 405) 5'- GAA AGC TGA GAT GGA GGG CGG CAT GGC GGG C-3' (FRAG 396) (SEQ. ID NO: 406) 5'- GAA AGC TGA GAT GGA GGG CGG CAT GGC GGG -3' (FRAG 397) (SEQ. ID NO: 407) 5'- GAA AGC TGA GAT GGA GGG CGG CAT GGC GG-3' (FRAG 398) (SEQ. ID NO: 408) 40 5'- GAA AGC TGA GAT GGA GGG CGG CAT GGC G-3' (FRAG 399) (SEQ. ID NO: 409) 5'- GAA AGC TGA GAT GGA GGG CGG CAT GGC -3' (FRAG 400) (SEQ. ID NO: 410) 5'- GAA AGC TGA GAT GGA GGG CGG CAT GG -3' (FRAG 401) (SEQ. ID NO: 411) 5'- GAA AGC TGA GAT GGA GGG CGG CAT G -3' (FRAG 402) (SEQ. ID NO: 412) 5'- GAA AGC TGA GAT GGA GGG CGG CAT -3' (FRAG 403) (SEQ. ID NO: 413) 45 5'- GAA AGC TGA GAT GGA GGG CGG CA-3' (FRAG 404) (SEQ. ID NO: 414) 5'- GAA AGC TGA GAT GGA GGG CGG C-3' (FRAG 405) (SEQ. ID NO: 415) 5'- GAA AGC TGA GAT GGA GGG CGG -3' (FRAG 406) (SEQ. ID NO: 416) 5'- GAA AGC TGA GAT GGA GGG CG -3' (FRAG 407) (SEQ. ID NO: 417) 5'- GAA AGC TGA GAT GGA GGG C -3' (FRAG 408) (SEQ. ID NO: 418) 50 5'- GAA AGC TGA GAT GGA GGG -3' (FRAG 409) (SEQ. ID NO: 419) 5'- GAA AGC TGA GAT GGA GG -3' (FRAG 410) (SEQ. ID NO: 420) 5'- GAA AGC TGA GAT GGA G -3' (FRAG 411) (SEQ. ID NO: 421) 5'- GAA AGC TGA GAT GGA -3' (FRAG 412) (SEQ. ID NO: 422) 5'- GAA AGC TGA GAT GG -3' (FRAG 413) (SEQ. ID NO: 423) 55 5'- GAA AGC TGA GAT G -3' (FRAG 414) (SEQ. ID NO: 424) 5'- GAA AGC TGA GAT -3' (FRAG 415) (SEQ. ID NO: 425) 5'- GAA AGC TGA GA-3' (FRAG 416) (SEQ. ID NO: 426) 5'- GAA AGC TGA G-3' (FRAG 417) (SEQ. ID NO: 427) 5'- AA AGC TGA GAT GGA GGG CGG CAT GGC GGG CAC AGG CTG GGC-3' (FRAG 418) (SEQ. ID NO: 428) 60 5'- AA AGC TGA GAT GGA GGG CGG CAT GGC GGG CAC AGG CTG GG-3' (FRAG 419) (SEQ. ID NO: 429) 5'- AA AGC TGA GAT GGA GGG CGG CAT GGC GGG CAC AGG CTG G-3' (FRAG 420) (SEQ. ID NO: 430) 5'- AA AGC TGA GAT GGA GGG CGG CAT GGC GGG CAC AGG CTG -3' (FRAG 421) (SEQ. ID NO: 431) 5'- AA AGC TGA GAT GGA GGG CGG CAT GGC GGG CAC AGG CT-3' (FRAG 422) (SEQ. ID NO: 432) 5'- AA AGC TGA GAT GGA GGG CGG CAT GGC GGG CAC AGG C-3' (FRAG 423) (SEQ. ID NO: 433) 65 5'- AA AGC TGA GAT GGA GGG CGG CAT GGC GGG CAC AGG -3'(FRAG 424) (SEQ. ID NO: 434) 5'- AA AGC TGA GAT GGA GGG CGG CAT GGC GGG CAC AG-3' (FRAG 425) (SEQ. ID NO: 435) WO 00/62736 PCT/USOO/08020 113 5'- AA AGC TGA GAT GGA GGG CGG CAT GGC GGG CAC A-3 (FRAG 426) (SEQ. ID NO: 436) 5'- AA AGC TGA GAT GGA GGG CGG CAT GGC GGG CAC-3' (FRAG 427) (SEQ. ID NO: 437) 5'- AA AGC TGA GAT GGA GGG CGG CAT GGC GGG CA-3' (FRAG 428) (SEQ. ID NO: 438) 5'- AA AGC TGA GAT GGA GGG CGG CAT GGC GGG C-3' (FRAG 429) (SEQ. ID NO: 439) 5 5'- AA AGC TGA GAT GGA GGG CGG CAT GGC GGG -3' (FRAG 430) (SEQ. ID NO: 440) 5'- AA AGC TGA GAT GGA GGG CGG CAT GGC GG-3' (FRAG 431) (SEQ. ID NO: 441) 5'- AA AGC TGA GAT GGA GGG CGG CAT GGC G-3' (FRAG 432) (SEQ. ID NO: 442) 5'- AA AGC TGA GAT GGA GGG CGG CAT GGC -3' (FRAG 433) (SEQ. ID NO: 443) 5'- AA AGC TGA GAT GGA GGG CGG CAT GG -3' (FRAG 434) (SEQ. ID NO: 444) 10 5'- AA AGC TGA GAT GGA GGG CGG CAT G -3' (FRAG 435) (SEQ. ID NO: 445) 5'- AA AGC TGA GAT GGA GGG CGG CAT -3' (FRAG 436) (SEQ. ID NO: 446) 5'- AA AGC TGA GAT GGA GGG CGG CA-3' (FRAG 437) (SEQ. ID NO: 447) 5'- AA AGC TGA GAT GGA GGG CGG C-3' (FRAG 438) (SEQ. ID NO: 448) 5'- AA AGC TGA GAT GGA GGG CGG -3' (FRAG 439) (SEQ. ID NO: 449) 15 5'- AA AGC TGA GAT GGA GGG CG -3' (FRAG 440) (SEQ. ID NO: 450) 5'- AA AGC TGA GAT GGA GGG C -3' (FRAG 441) (SEQ. ID NO: 451) 5'- AA AGC TGA GAT GGA GGG -3' (FRAG 442) (SEQ. ID NO: 452) 5'- AA AGC TGA GAT GGA GG -3' (FRAG 443) (SEQ. ID NO: 453) 5'- AA AGC TGA GAT GGA G -3' (FRAG 444) (SEQ. ID NO: 454) 20 5'- AA AGC TGA GAT GGA -3' (FRAG 445) (SEQ. ID NO: 455) 5'- AA AGC TGA GAT GG -3' (FRAG 446) (SEQ. ID NO: 456) 5'- AA AGC TGA GAT G -3' (FRAG 447) (SEQ. ID NO: 457) 5'- AA AGC TGA GAT -3' (FRAG 448) (SEQ. ID NO: 458) 5'- AA AGC TGA GA-3' (FRAG 449) (SEQ. ID NO: 459) 25 5'- A AGC TGA GAT GGA GGG CG G CAT GGC GGG CAC AGG CTG GGC-3' (FRAG 450) (SEQ. ID NO: 460) 5'- A AGC TGA GAT GGA GGG CGG CAT GGC GGG CAC AGG CTG GG-3' (FRAG 451) (SEQ. ID NO: 461) 5'- A AGC TGA GAT GGA GGG CGG CAT GGC GGG CAC AGG CTG G-3' (FRAG 452) (SEQ. ID NO: 462) 5'- A AGC TGA GAT GGA GGG CGG CAT GGC GGG CAC AGG CTG -3' (FRAG 453) (SEQ. ID NO: 463) 5'- A AGC TGA GAT GGA GGG CGG CAT GGC GGG CAC AGG CT-3' (FRAG 454) (SEQ. ID NO: 464) 30 5'- A AGC TGA GAT GGA GGG CGG CAT GGC GGG CAC AGG C-3' (FRAG 455) (SEQ. ID NO: 465) 5'- A AGC TGA GAT GGA GGG CGG CAT GGC GGG CAC AGG -3' (FRAG 456) (SEQ. ID NO: 466) 5'- A AGC TGA GAT GGA GGG CGG CAT GGC GGG CAC AG-3' (FRAG 457) (SEQ. ID NO: 467) 5'- A AGC TGA GAT GGA GGG CGG CAT GGC GGG CAC A-3' (FRAG 458) (SEQ. ID NO: 468) 5'- A AGC TGA GAT GGA GGG CGG CAT GGC GGG CAC-3' (FRAG 459) (SEQ. ID NO: 469) 35 5'- A AGC TGA GAT GGA GGG CGG CAT GGC GGG CA-3' (FRAG 460) (SEQ. ID NO: 470) 5'- A AGC TGA GAT GGA GGG CGG CAT GGC GGG C-3' (FRAG 461) (SEQ. ID NO: 471) 5'- A AGC TGA GAT GGA GGG CGG CAT GGC GGG -3' (FRAG 462) (SEQ. ID NO: 472) 5'- A AGC TGA GAT GGA GGG CGG CAT GGC GG-3' (FRAG 463) (SEQ. ID NO: 473) 5'- A AGC TGA GAT GGA GGG CGG CAT GGC G-3' (FRAG 464) (SEQ. ID NO: 474) 40 5'- A AGC TGA GAT GGA GGG CGG CAT GGC -3' (FRAG 465) (SEQ. ID NO: 475) 5'- A AGC TGA GAT GGA GGG CGG CAT GG -3' (FRAG 466) (SEQ. ID NO: 476) 5'- A AGC TGA GAT GGA GGG CGG CAT G -3' (FRAG 467) (SEQ. ID NO: 477) 5'- A AGC TGA GAT GGA GGG CGG CAT -3' (FRAG 468) (SEQ. ID NO: 478) 5'- A AGC TGA GAT GGA GGG CGG CA-3' (FRAG 469) (SEQ. ID NO: 479) 45 5'- A AGC TGA GAT GGA GGG CGG C-3' (FRAG 470) (SEQ. ID NO: 480) 5'- A AGC TGA GAT GGA GGG CGG -3' (FRAG 471) (SEQ. ID NO: 481) 5'- A AGC TGA GAT GGA GGG CG -3' (FRAG 472) (SEQ. ID NO: 482) 5'- A AGC TGA GAT GGA GGG C -3' (FRAG 473) (SEQ. ID NO: 483) 5'- A AGC TGA GAT GGA GGG -3' (FRAG 474) (SEQ. ID NO: 484) 50 5'- A AGC TGA GAT GGA GG -3' (FRAG 475) (SEQ. ID NO: 485) 5'- A AGC TGA GAT GGA G -3' (FRAG 476) (SEQ. ID NO: 486) 5'- A AGC TGA GAT GGA -3' (FRAG 477) (SEQ. ID NO: 487) 5'- A AGC TGA GAT GG -3' (FRAG 478) (SEQ. ID NO: 488) 5'- A AGC TGA GAT G -3' (FRAG 479) (SEQ. ID NO: 489) 55 5'- A AGC TGA GAT -3' (FRAG 480) (SEQ. ID NO: 490) 5'- AGC TGA GAT GGA GGG CGG CAT GGC GGG CAC AGG CTG GGC-3' (FRAG 481) (SEQ. ID NO: 491) 5'- AGC TGA GAT GGA GGG CGG CAT GGC GGG CAC AGG CTG GG-3' (FRAG 482) (SEQ. ID NO: 492) 5'- AGC TGA GAT GGA GGG CGG CAT GGC GGG CAC AGG CTG G-3' (FRAG 483) (SEQ. ID NO: 493) 5'- AGC TGA GAT GGA GGG CGG CAT GGC GGG CAC AGG CTG -3' (FRAG 484) (SEQ. ID NO: 494) 60 5'- AGC TGA GAT GGA GGG CGG CAT GGC GGG CAC AGG CT-3' (FRAG 485) (SEQ. ID NO: 495) 5'- AGC TGA GAT GGA GGG CGG CAT GGC GGG CAC AGG C-3' (FRAG 486) (SEQ. ID NO: 496) 5'- AGC TGA GAT GGA GGG CGG CAT GGC GGG CAC AGG -3' (FRAG 487) (SEQ. ID NO: 497) 5'- AGC TGA GAT GGA GGG CGG CAT GGC GGG CAC AG-3' (FRAG 488) (SEQ. ID NO: 498) 5'- AGC TGA GAT GGA GGG CGG CAT GGC GGG CAC A-3' (FRAG 489) (SEQ. ID NO: 499) 65 5'- AGC TGA GAT GGA GGG CGG CAT GGC GGG CAC-3' (FRAG 490) (SEQ. ID NO: 500) 5'- AGC TGA GAT GGA GGG CGG CAT GGC GGG CA-3' (FRAG 491) (SEQ. ID NO: 501) WO 00/62736 PCT/USOO/08020 114 5'- AGC TGA GAT GGA GGG CGG CAT GGC GGG C-3' (FRAG 492) (SEQ. ID NO: 502) 5'- AGC TGA GAT GGA GGG CGG CAT GGC GGG -3' (FRAG 493) (SEQ. ID NO: 503) 5'- AGC TGA GAT GGA GGG CGG CAT GGC GG-3' (FRAG 494) (SEQ. ID NO: 504) 5'- AGC TGA GAT GGA GGG CGG CAT GGC G-3' (FRAG 495) (SEQ. ID NO: 505) 5 5'- AGC TGA GAT GGA GGG CGG CAT GGC -3' (FRAG 496) (SEQ. ID NO: 506) 5'- AGC TGA GAT GGA GGG CGG CAT GG -3' (FRAG 497) (SEQ. ID NO: 507) 5'- AGC TGA GAT GGA GGG CGG CAT G -3' (FRAG 498) (SEQ. ID NO: 508) 5'- AGC TGA GAT GGA GGG CGG CAT -3' (FRAG 499) (SEQ. ID NO: 509) 5'- AGC TGA GAT GGA GGG CGG CA-3' (FRAG 500) (SEQ. ID NO: 510) 10 5'- AGC TGA GAT GGA GGG CGG C-3' (FRAG 501) (SEQ. ID NO: 511) 5'- AGC TGA GAT GGA GGG CGG -3' (FRAG 502) (SEQ. ID NO: 512) 5'- AGC TGA GAT GGA GGG CG -3' (FRAG 503) (SEQ. ID NO: 513) 5'- AGC TGA GAT GGA GGG C -3' (FRAG 504) (SEQ. ID NO: 514) 5'- AGC TGA GAT GGA GGG -3' (FRAG 505) (SEQ. ID NO: 515) 15 5'- AGC TGA GAT GGA GG -3' (FRAG 506) (SEQ. ID NO: 516) 5'- AGC TGA GAT GGA G -3' (FRAG 507) (SEQ. ID NO: 517) 5'- AGC TGA GAT GGA -3' (FRAG 508) (SEQ. ID NO: 518) 5'- AGC TGA GAT GG -3' (FRAG 509) (SEQ. ID NO: 519) 5'- AGC TGA GAT G -3' (FRAG 510) (SEQ. ID NO: 520) 20 5'- GC TGA GAT GGA GGG CGG CAT GGC GGG CAC AGG CTG GGC-3' (FRAG 511) (SEQ. ID NO: 521) 5'- GC TGA GAT GGA GGG CGG CAT GGC GGG CAC AGG CTG GG-3' (FRAG 512) (SEQ. ID NO: 522) 5'- GC TGA GAT GGA GGG CGG CAT GGC GGG CAC AGG CTG G-3' (FRAG 513) (SEQ. ID NO: 523) 5'- GC TGA GAT GGA GGG CGG CAT GGC GGG CAC AGG CTG -3' (FRAG 514) (SEQ. ID NO: 524) 5'- GC TGA GAT GGA GGG CGG CAT GGC GGG CAC AGG CT-3' (FRAG 515) (SEQ. ID NO: 525) 25 5'- GC TGA GAT GGA GGG CGG CAT GGC GGG CAC AGG C-3' (FRAG 516) (SEQ. ID NO: 526) 5'- GC TGA GAT GGA GGG CGG CAT GGC GGG CAC AGG -3' (FRAG 517) (SEQ. ID NO: 527) 5'- GC TGA GAT GGA GGG CGG CAT GGC GGG CAC AG-3' (FRAG 518) (SEQ. ID NO: 528) 5'- GC TGA GAT GGA GGG CGG CAT GGC GGG CAC A-3' (FRAG 519) (SEQ. ID NO: 529) 5'- GC TGA GAT GGA GGG CGG CAT GGC GGG CAC-3' (FRAG 520) (SEQ. ID NO: 530) 30 5'- GC TGA GAT GGA GGG CGG CAT GGC GGG CA-3' (FRAG 521) (SEQ. ID NO: 531) 5'- GC TGA GAT GGA GGG CGG CAT GGC GGG C-3' (FRAG 522) (SEQ. ID NO: 532) 5'- GC TGA GAT GGA GGG CGG CAT GGC GGG -3' FRAGG 523) (SEQ. ID NO: 533) 5'- GC TGA GAT GGA GGG CGG CAT GGC GG-3' (FRAG 524) (SEQ. ID NO: 534) 5'- GC TGA GAT GGA GGG CGG CAT GGC G-3' (FRAG 525) (SEQ. ID NO: 535) 35 5'- GC TGA GAT GGA GGG CGG CAT GGC -3' (FRAG 526) (SEQ. ID NO: 536) 5'- GC TGA GAT GGA GGG CGG CAT GG -3' (FRAG 527) (SEQ. ID NO: 537) 5'- GC TGA GAT GGA GGG CGG CAT G -3' (FRAG 528) (SEQ. ID NO: 538) 5'- GC TGA GAT GGA GGG CGG CAT -3' (FRAG 529) (SEQ. ID NO: 539) 5'- GC TGA GAT GGA GGG CGG CA-3' (FRAG 530) (SEQ. ID NO: 540) 40 5'- GC TGA GAT GGA GGG CGG C-3' (FRAG 531) (SEQ. 1D NO: 541) 5'- GC TGA GAT GGA GGG CGG -3' (FRAG 532) (SEQ. ID NO: 542) 5'- GC TGA GAT GGA GGG CG -3' (FRAG 533) (SEQ. ID NO: 543) 5'- GC TGA GAT GGA GGG C -3' (FRAG 534) (SEQ. 1D NO: 544) 5'- GC TGA GAT GGA GGG -3' FRAGG 535) (SEQ. ID NO: 545) 45 5'- GC TGA GAT GGA GG -3' (FRAG 536) (SEQ. ID NO: 546) 5'- GC TGA GAT GGA G -3' (FRAG 537) (SEQ. ID NO: 547) 5'- GC TGA GAT GGA -3' (FRAG 538) (SEQ. ID NO: 548) 5'- GC TGA GAT GG -3' (FRAG 539) (SEQ. ID NO: 549) 5'- C TGA GAT GGA GGG CGG CAT GGC GGG CAC AGG CTG GGC-3' (FRAG 540) (SEQ. ID NO: 550) 50 5'- C TGA GAT GGA GGG CGG CAT GGC GGG CAC AGG CTG GG-3' (FRAG 541) (SEQ. ID NO: 551) 5'- C TGA GAT GGA GGG CGG CAT GGC GGG CAC AGG CTG G-3' FRAGG 542) (SEQ. 1ID NO: 552) 5'- C TGA GAT GGA GGG CGG CAT GGC GGG CAC AGG CTG -3' (FRAG 543) (SEQ. ID NO: 553) 5'- C TGA GAT GGA GGG CGG CAT GGC GGG CAC AGG CT-3' (FRAG 544) (SEQ. ID NO: 554) 5'- C TGA GAT GGA GGG CGG CAT GGC GGG CAC AGG C-3' (FRAG 545) (SEQ. ID NO: 555) 55 5'- C TGA GAT GGA GGG CGG CAT GGC GGG CAC AGG -3' (FRAG 546) (SEQ. ID NO: 556) 5'- C TGA GAT GGA GGG CGG CAT GGC GGG CAC AG-3' (FRAG 547) (SEQ. ID NO: 557) 5'- C TGA GAT GGA GGG CGG CAT GGC GGG CAC A-3' (FRAG 548) (SEQ. ID NO: 558) 5'- C TGA GAT GGA GGG CGG CAT GGC GGG CAC-3' (FRAG 549) (SEQ. ID NO: 559) 5'- C TGA GAT GGA GGG CGG CAT GGC GGG CA-3' (FRAG 550) (SEQ. ID NO: 560) 60 5'- C TGA GAT GGA GGG CGG CAT GGC GGG C-3' (FRAG 551) (SEQ. ID NO: 561) 5'- C TGA GAT GGA GGG CGG CAT GGC GGG -3' (FRAG 552) (SEQ. ID NO: 562) 5'- C TGA GAT GGA GGG CGG CAT GGC GG-3' (FRAG 553) (SEQ. ID NO: 563) 5'- C TGA GAT GGA GGG CGG CAT GGC G-3' (FRAG 554) (SEQ. ID NO: 564) 5'- C TGA GAT GGA GGG CGG CAT GGC -3' (FRAG 555) (SEQ. ID NO: 565) 65 5'- C TGA GAT GGA GGG CGG CAT GG -3' (FRAG 556) (SEQ. ID NO: 566) 5'- C TGA GAT GGA GGG CGG CAT G -3' (FRAG 557) (SEQ. ID NO: 567) WO 00/62736 PCT/USOO/08020 115 5'- C TGA GAT GGA GGG CGG CAT -3' (FRAG 558) (SEQ. ID NO: 568) 5'- C TGA GAT GGA GGG CGG CA-3' (FRAG 559) (SEQ. ID NO: 569) 5'- C TGA GAT GGA GGG CGG C-3' (FRAG 560) (SEQ. ID NO: 570) 5'- C TGA GAT GGA GGG CGG -3' (FRAG 561) (SEQ. ID NO: 571) 5 5'- C TGA GAT GGA GGG CG -3' (FRAG 562) (SEQ. ID NO: 572) 5'- C TGA GAT GGA GGG C -3' (FRAG 563) (SEQ. ID NO: 573) 5'- C TGA GAT GGA GGG -3' (FRAG 564) (SEQ. ID NO: 574) 5'- C TGA GAT GGA GG -3' (FRAG 565) (SEQ. ID NO: 575) 5'- C TGA GAT GGA G -3' (FRAG 566) (SEQ. ID NO: 576) 10 5'- C TGA GAT GGA -3' (FRAG 567) (SEQ. ID NO: 577) 5'- TGA GAT GGA GGG CGG CAT GGC GGG CAC AGG CTG GGC-3' (FRAG 568) (SEQ. ID NO: 578) 5'- TGA GAT GGA GGG CGG CAT GGC GGG CAC AGG CTG GG-3' (FRAG 569) (SEQ. ID NO: 579) 5'- TGA GAT GGA GGG CGG CAT GGC GGG CAC AGG CTG G-3' (FRAG 570) (SEQ. ID NO: 580) 5'- TGA GAT GGA GGG CGG CAT GGC GGG CAC AGG CTG -3' (FRAG 571) (SEQ. ID NO: 581) 15 5'- TGA GAT GGA GGG CGG CAT GGC GGG CAC AGG CT-3' (FRAG 572) (SEQ. ID NO: 582) 5'- TGA GAT GGA GGG CGG CAT GGC GGG CAC AGG C-3' (FRAG 573) (SEQ. ID NO: 583) 5'- TGA GAT GGA GGG CGG CAT GGC GGG CAC AGG -3' (FRAG 574) (SEQ. ID NO: 584) 5'- TGA GAT GGA GGG CGG CAT GGC GGG CAC AG-3' (FRAG 575) (SEQ. ID NO: 585) 5'- TGA GAT GGA GGG CGG CAT GGC GGG CAC A-3' (FRAG 576) (SEQ. ID NO: 586) 20 5'- TGA GAT GGA GGG CGG CAT GGC GGG CAC-3' (FRAG 577) (SEQ. ID NO: 587) 5'- TGA GAT GGA GGG CGG CAT GGC GGG CA-3' (FRAG 578) (SEQ. ID NO: 588) 5'- TGA GAT GGA GGG CGG CAT GGC GGG C-3' (FRAG 579) (SEQ. ID NO: 589) 5'- TGA GAT GGA GGG CGG CAT GGC GGG -3' (FRAG 580) (SEQ. ID NO: 590) 5'- TGA GAT GGA GGG CGG CAT GGC GG-3' (FRAG 581) (SEQ. ID NO: 591) 25 5'- TGA GAT GGA GGG CGG CAT GGC G-3' FRAGG 582) (SEQ. ID NO: 592) 5'- TGA GAT GGA GGG CGG CAT GGC -3' (FRAG 583) (SEQ. ID NO: 593) 5'- TGA GAT GGA GGG CGG CAT GG -3' (FRAG 584) (SEQ. ID NO: 594) 5'- TGA GAT GGA GGG CGG CAT G -3' FRAGG 585) (SEQ. ID NO: 595) 5'- TGA GAT GGA GGG CGG CAT -3' (FRAG 586) (SEQ. ID NO: 596) 30 5'- TGA GAT GGA GGG CGG CA-3' (FRAG 587) (SEQ. ID NO: 597) 5'- TGA GAT GGA GGG CGG C-3' (FRAG 588) (SEQ. ID NO: 598) 5'- TGA GAT GGA GGG CGG -3' FRAGG 589) (SEQ. ID NO: 599) 5'- TGA GAT GGA GGG CG -3' (FRAG 590) (SEQ. ID NO: 600) 5'- TGA GAT GGA GGG C -3' (FRAG 591) (SEQ. ID NO: 601) 35 5'- TGA GAT GGA GGG -3' FRAGG 592) (SEQ. ID NO: 602) 5'- TGA GAT GGA GG -3' (FRAG 593) (SEQ. ID NO: 603) 5'- TGA GAT GGA G -3' FRAGG 594) (SEQ. ID NO: 604) 5'- GA GAT GGA GGG CGG CAT GGC GGG CAC AGG CTG GGC-3' (FRAG 595) (SEQ. ID NO: 605) 5'- GA GAT GGA GGG CGG CAT GGC GGG CAC AGG CTG GG-3' (FRAG 596) (SEQ. ID NO: 606) 40 5'- GA GAT GGA GGG CGG CAT GGC GGG CAC AGG CTG G-3' FRAGG 597) (SEQ. ID NO: 607) 5'- GA GAT GGA GGG CGG CAT GGC GGG CAC AGG CTG -3' (FRAG 598) (SEQ. ID NO: 608) 5'- GA GAT GGA GGG CGG CAT GGC GGG CAC AGG CT-3' (FRAG 599) (SEQ. ID NO: 609) 5'- GA GAT GGA GGG CGG CAT GGC GGG CAC AGG C-3' (FRAG 600) (SEQ. ID NO: 610) 5'- GA GAT GGA GGG CGG CAT GGC GGG CAC AGG -3' (FRAG 601) (SEQ. ID NO: 611) 45 5'- GA GAT GGA GGG CGG CAT GGC GGG CAC AG-3' (FRAG 602) (SEQ. ID NO: 612) 5'- GA GAT GGA GGG CGG CAT GGC GGG CAC A-3' FRAGG 603) (SEQ. ID NO: 613) 5'- GA GAT GGA GGG CGG CAT GGC GGG CAC-3' (FRAG 604) (SEQ. ID NO: 614) 5'- GA GAT GGA GGG CGG CAT GGC GGG CA-3' (FRAG 605) (SEQ. ID NO: 615) 5'- GA GAT GGA GGG CGG CAT GGC GGG C-3' (FRAG 606) (SEQ. ID NO: 616) 50 5'- GA GAT GGA GGG CGG CAT GGC GGG -3' (FRAG 607) (SEQ. ID NO: 617) 5'- GA GAT GGA GGG CGG CAT GGC GG-3' (FRAG 608) (SEQ. ID NO: 618) 5'- GA GAT GGA GGG CGG CAT GGC G-3' (FRAG 609) (SEQ. ID NO: 619) 5'- GA GAT GGA GGG CGG CAT GGC -3' (FRAG 610) (SEQ. ID NO: 620) 5'- GA GAT GGA GGG CGG CAT GG -3' (FRAG 611) (SEQ. ID NO: 621) 55 5'- GA GAT GGA GGG CGG CAT G -3' (FRAG 612) (SEQ. ID NO: 622) 5'- GA GAT GGA GGG CGG CAT -3' (FRAG 613) (SEQ. ID NO: 623) 5'- GA GAT GGA GGG CGG CA-3' (FRAG 614) (SEQ. ID NO: 624) 5'- GA GAT GGA GGG CGG C-3' (FRAG 615) (SEQ. ID NO: 625) 5'- GA GAT GGA GGG CGG -3' (FRAG 616) (SEQ. ID NO: 626) 60 5'- GA GAT GGA GGG CG -3' (FRAG 617) (SEQ. ID NO: 627) 5'- GA GAT GGA GGG C -3' (FRAG 618) (SEQ. ID NO: 628) 5'- GA GAT GGA GGG -3' (FRAG 619) (SEQ. ID NO: 629) 5'- GA GAT GGA GG -3' (FRAG 620) (SEQ. ID NO: 630) 5'- A GAT GGA GGG CGG CAT GGC GGG CAC AGG CTG GGC-3' (FRAG 621) (SEQ. ID NO: 631) 65 5'- A GAT GGA GGG CGG CAT GGC GGG CAC AGG CTG GG-3' (FRAG 622) (SEQ. ID NO: 632) 5'- A GAT GGA GGG CGG CAT GGC GGG CAC AGG CTG G-3' (FRAG 623) (SEQ. ID NO: 633) WO 00/62736 PCT/US00/08020 116 5'- A GAT GGA GGG CGG CAT GGC GGG CAC AGG CTG -3' (FRAG 624) (SEQ. ID NO: 634) 5'- A GAT GGA GGG CGG CAT GGC GGG CAC AGG CT-3' (FRAG 625) (SEQ. ID NO: 635) 5'- A GAT GGA GGG CGG CAT GGC GGG CAC AGG C-3' (FRAG 626) (SEQ. ID NO: 636) 5'- A GAT GGA GGG CGG CAT GGC GGG CAC AGG -3' (FRAG 627) (SEQ. ID NO: 637) 5 5'- A GAT GGA GGG CGG CAT GGC GGG CAC AG-3' (FRAG 628) (SEQ. ID NO: 638) 5'- A GAT GGA GGG CGG CAT GGC GGG CAC A-3' (FRAG 629) (SEQ. ID NO: 639) 5'- A GAT GGA GGG CGG CAT GGC GGG CAC-3' (FRAG 630) (SEQ. ID NO: 640) 5'- A GAT GGA GGG CGG CAT GGC GGG CA-3' (FRAG 631) (SEQ. ID NO: 641) 5'- A GAT GGA GGG CGG CAT GGC GGG C-3' (FRAG 632) (SEQ. ID NO: 642) 10 5'- A GAT GGA GGG CGG CAT GGC GGG -3' (FRAG 633) (SEQ. ID NO: 643) 5'- A GAT GGA GGG CGG CAT GGC GG-3' (FRAG 634) (SEQ. ID NO: 644) 5'- A GAT GGA GGG CGG CAT GGC G-3' (FRAG 635) (SEQ. ID NO: 645) 5'- A GAT GGA GGG CGG CAT GGC -3' (FRAG 636) (SEQ. ID NO: 646) 5'- A GAT GGA GGG CGG CAT GG -3' (FRAG 637) (SEQ. ID NO: 647) 15 5'- A GAT GGA GGG CGG CAT G -3' (FRAG 638) (SEQ. ID NO: 648) 5'- A GAT GGA GGG CGG CAT -3' (FRAG 639) (SEQ. ID NO: 649) 5'- A GAT GGA GGG CGG CA-3' (FRAG 640) (SEQ. ID NO: 650) 5'- A GAT GGA GGG CGG C-3' (FRAG 641) (SEQ. ID NO: 651) 5'- A GAT GGA GGG CGG -3' (FRAG 642) (SEQ. ID NO: 652) 20 5'- A GAT GGA GGG CG -3' (FRAG 643) (SEQ. ID NO: 653) 5'- A GAT GGA GGG C -3' (FRAG 644) (SEQ. ID NO: 654) 5'- A GAT GGA GGG -3' FRAGG 645) (SEQ. ID NO: 655) 5'- GAT GGA GGG CGG CAT GGC GGG CAC AGG CTG GGC-3' (FRAG 646) (SEQ. ID NO: 656) 5'- GAT GGA GGG CGG CAT GGC GGG CAC AGG CTG GG-3' (FRAG 647) (SEQ. ID NO: 657) 25 5'- GAT GGA GGG CGG CAT GGC GGG CAC AGG CTG G-3' (FRAG 648) (SEQ. ID NO: 658) 5'- GAT GGA GGG CGG CAT GGC GGG CAC AGG CTG -3' (FRAG 6) (SEQ. ID NO: 659) 5'- GAT GGA GGG CGG CAT GGC GGG CAC AGG CT-3' (FRAG 650) (SEQ. ID NO: 660) 5'- GAT GGA GGG CGG CAT GGC GGG CAC AGG C-3' (FRAG 651) (SEQ. ID NO: 661) 5'- GAT GGA GGG CGG CAT GGC GGG CAC AGG -3' (FRAG 652) (SEQ. ID NO: 662) 30 5'- GAT GGA GGG CGG CAT GGC GGG CAC AG-3' FRAGG 653) (SEQ. ID NO: 663) 5'- GAT GGA GGG CGG CAT GGC GGG CAC A-3' (FRAG 654) (SEQ. ID NO: 664) 5'- GAT GGA GGG CGG CAT GGC GGG CAC-3' (FRAG 655) (SEQ. ID NO: 665) 5'- GAT GGA GGG CGG CAT GGC GGG CA-3' (FRAG 656) (SEQ. ID NO: 666) 5'- GAT GGA GGG CGG CAT GGC GGG C-3' (FRAG 657) (SEQ. ID NO: 667) 35 5'- GAT GGA GGG CGG CAT GGC GGG -3' (FRAG 658) (SEQ. ID NO: 668) 5'- GAT GGA GGG CGG CAT GGC GG-3' FRAGG 659) (SEQ. ID NO: 669) 5'- GAT GGA GGG CGG CAT GGC G-3' FRAGG 660) (SEQ. ID NO: 670) 5'- GAT GGA GGG CGG CAT GGC -3' (FRAG 661) (SEQ. ID NO: 671) 5'- GAT GGA GGG CGG CAT GG -3' (FRAG 662) (SEQ. ID NO: 672) 40 5'- GAT GGA GGG CGG CAT G -3' (FRAG 663) (SEQ. ID NO: 673) 5'- GAT GGA GGG CGG CAT -3' (FRAG 664) (SEQ. ID NO: 674) 5'- GAT GGA GGG CGG CA-3' (FRAG 665) (SEQ. ID NO: 675) 5'- GAT GGA GGG CGG C-3' (FRAG 666) (SEQ. ID NO: 676) 5'- GAT GGA GGG CGG -3' FRAGG 667) (SEQ. ID NO: 677) 45 5'- GAT GGA GGG CG -3' (FRAG 668) (SEQ. ID NO: 678) 5'- GAT GGA GGG C -3' (FRAG 669) (SEQ. ID NO: 679) 5'- AT GGA GGG CGG CAT GGC GGG CAC AGG CTG GGC-3' (FRAG 670) (SEQ. ID NO: 680) 5'- AT GGA GGG CGG CAT GGC GGG CAC AGG CTG GG-3' (FRAG 671) (SEQ. ID NO: 681) 5'- AT GGA GGG CGG CAT GGC GGG CAC AGG CTG G-3' (FRAG 672) (SEQ. ID NO: 682) 50 5'- AT GGA GGG CGG CAT GGC GGG CAC AGG CTG -3' (FRAG 673) (SEQ. ID NO: 683) 5'- AT GGA GGG CGG CAT GGC GGG CAC AGG CT-3' (FRAG 674) (SEQ. ID NO: 684) 5'- AT GGA GGG CGG CAT GGC GGG CAC AGG C-3' (FRAG 675) (SEQ. ID NO: 685) 5'- AT GGA GGG CGG CAT GGC GGG CAC AGG -3' (FRAG 676) (SEQ. ID NO: 686) 5'- AT GGA GGG CGG CAT GGC GGG CAC AG-3' (FRAG 677) (SEQ. ID NO: 687) 55 5'- AT GGA GGG CGG CAT GGC GGG CAC A-3' (FRAG 678) (SEQ. ID NO: 688) 5'- AT GGA GGG CGG CAT GGC GGG CAC-3' (FRAG 679) (SEQ. ID NO: 689) 5'- AT GGA GGG CGG CAT GGC GGG CA-3' (FRAG 680) (SEQ. ID NO: 690) 5'- AT GGA GGG CGG CAT GGC GGG C-3' (FRAG 681) (SEQ. ID NO: 691) 5'- AT GGA GGG CGG CAT GGC GGG -3' (FRAG 682) (SEQ. ID NO: 692) 60 5'- AT GGA GGG CGG CAT GGC GG-3' (FRAG 683) (SEQ. ID NO: 693) 5'- AT GGA GGG CGG CAT GGC G-3' (FRAG 684) (SEQ. ID NO: 694) 5'- AT GGA GGG CGG CAT GGC -3' (FRAG 685) (SEQ. ID NO: 695) 5'- AT GGA GGG CGG CAT GG -3' (FRAG 686) (SEQ. ID NO: 696) 5'- AT GGA GGG CGG CAT G -3' (FRAG 687) (SEQ. ID NO: 697) 65 5'- AT GGA GGG CGG CAT -3' (FRAG 688) (SEQ. ID NO: 698) 5'- AT GGA GGG CGG CA-3' (FRAG 689) (SEQ. ID NO: 699) WO 00/62736 PCT/USOO/08020 117 5'- AT GGA GGG CGG C-3' (FRAG 690) (SEQ. ID NO: 700) 5'- AT GGA GGG CGG -3' (FRAG 691) (SEQ. ID NO: 701) 5'- AT GGA GGG CG -3' (FRAG 692) (SEQ. ID NO: 702) 5'- T GGA GGG CGG CAT GGC GGG CAC AGG CTG GGC-3' (FRAG 693) (SEQ. ID NO: 703) 5 5'- T GGA GGG CGG CAT GGC GGG CAC AGG CTG GG-3' (FRAG 694) (SEQ. ID NO: 704) 5'- T GGA GGG CGG CAT GGC GGG CAC AGG CTG G-3' (FRAG 695) (SEQ. ID NO: 705) 5'- T GGA GGG CGG CAT GGC GGG CAC AGG CTG -3' (FRAG 696) (SEQ. ID NO: 706) 5'- T GGA GGG CGG CAT GGC GGG CAC AGG CT-3' (FRAG 697) (SEQ. ID NO: 707) 5'- T GGA GGG CGG CAT GGC GGG CAC AGG C-3' (FRAG 698) (SEQ. ID NO: 708) 10 5'- T GGA GGG CGG CAT GGC GGG CAC AGG -3' (FRAG 699) (SEQ. ID NO: 709) 5'- T GGA GGG CGG CAT GGC GGG CAC AG-3' (FRAG 700) (SEQ. ID NO: 710) 5'- T GGA GGG CGG CAT GGC GGG CAC A-3' (FRAG 701) (SEQ. ID NO: 711) 5'- T GGA GGG CGG CAT GGC GGG CAC-3' (FRAG 702) (SEQ. ID NO: 712) 5'- T GGA GGG CGG CAT GGC GGG CA-3' (FRAG 703) (SEQ. ID NO: 713) 15 5'- T GGA GGG CGG CAT GGC GGG C-3' (FRAG 704) (SEQ. ID NO: 714) 5'- T GGA GGG CGG CAT GGC GGG -3' (FRAG 705) (SEQ. ID NO: 715) 5'- T GGA GGG CGG CAT GGC GG-3' (FRAG 706) (SEQ. ID NO: 716) 5'- T GGA GGG CGG CAT GGC G-3' (FRAG 707) (SEQ. ID NO: 717) 5'- T GGA GGG CGG CAT GGC -3' (FRAG 708) (SEQ. ID NO: 718) 20 5'- T GGA GGG CGG CAT GG -3' (FRAG 709) (SEQ. ID NO: 719) 5'- T GGA GGG CGG CAT G -3' (FRAG 710) (SEQ. ID NO: 720) 5'- T GGA GGG CGG CAT -3' (FRAG 711) (SEQ. ID NO: 721) 5'- T GGA GGG CGG CA-3' (FRAG 712) (SEQ. ID NO: 722) 5'- T GGA GGG CGG C-3' (FRAG 713) (SEQ. ID NO: 723) 25 5'- T GGA GGG CGG -3' (FRAG 714) (SEQ. ID NO: 724) 5'- GGA GGG CGG CAT GGC GGG CAC AGG CTG GGC-3' (FRAG 715) (SEQ. ID NO: 725) 5'- GGA GGG CGG CAT GGC GGG CAC AGG CTG GG-3' (FRAG 716) (SEQ. ID NO: 726) 5'- GGA GGG CGG CAT GGC GGG CAC AGG CTG G-3' (FRAG 717) (SEQ. ID NO: 727) 5'- GGA GGG CGG CAT GGC GGG CAC AGG CTG -3' (FRAG 718) (SEQ. ID NO: 728) 30 5'- GGA GGG CGG CAT GGC GGG CAC AGG CT-3' (FRAG 719) (SEQ. ID NO: 729) 5'- GGA GGG CGG CAT GGC GGG CAC AGG C-3' (FRAG 720) (SEQ. ID NO: 730) 5'- GGA GGG CGG CAT GGC GGG CAC AGG -3' (FRAG 721) (SEQ. ID NO: 731) 5'- GGA GGG CGG CAT GGC GGG CAC AG-3' (FRAG 722) (SEQ. ID NO: 732) 5'- GGA GGG CGG CAT GGC GGG CAC A-3' (FRAG 723) (SEQ. ID NO: 733) 35 5'- GGA GGG CGG CAT GGC GGG CAC-3' (FRAG 724) (SEQ. ID NO: 734) 5'- GGA GGG CGG CAT GGC GGG CA-3' (FRAG 725) (SEQ. ID NO: 735) 5'- GGA GGG CGG CAT GGC GGG C-3' (FRAG 726) (SEQ. ID NO: 736) 5'- GGA GGG CGG CAT GGC GGG -3' (FRAG 727) (SEQ. ID NO: 737) 5'- GGA GGG CGG CAT GGC GG-3' (FRAG 728) (SEQ. ID NO: 738) 40 5'- GGA GGG CGG CAT GGC G-3' (FRAG 729) (SEQ. ID NO: 739) 5'- GGA GGG CGG CAT GGC -3' (FRAG 730) (SEQ. ID NO: 740) 5'- GGA GGG CGG CAT GG -3' (FRAG 731) (SEQ. ID NO: 741) 5'- GGA GGG CGG CAT G -3' (FRAG 732) (SEQ. ID NO: 742) 5'- GGA GGG CGG CAT -3' (FRAG 733) (SEQ. ID NO: 743) 45 5'- GGA GGG CGG CA-3' (FRAG 734) (SEQ. ID NO: 744) 5'- GGA GGG CGG C-3' (FRAG 735) (SEQ. ID NO: 745) 5'- GA GGG CGG CAT GGC GGG CAC AGG CTG GGC-3' (FRAG 736) (SEQ. ID NO: 746) 5'- GA GGG CGG CAT GGC GGG CAC AGG CTG GG-3' (FRAG 737) (SEQ. ID NO: 747) 5'- GA GGG CGG CAT GGC GGG CAC AGG CTG G-3' (FRAG 738) (SEQ. ID NO: 748) 50 5'- GA GGG CGG CAT GGC GGG CAC AGG CTG -3' (FRAG 739) (SEQ. ID NO: 749) 5'- GA GGG CGG CAT GGC GGG CAC AGG CT-3' (FRAG 740) (SEQ. ID NO: 750) 5'- GA GGG CGG CAT GGC GGG CAC AGG C-3' (FRAG 741) (SEQ. ID NO: 751) 5'- GA GGG CGG CAT GGC GGG CAC AGG -3' (FRAG 742) (SEQ. ID NO: 752) 5'- GA GGG CGG CAT GGC GGG CAC AG-3' (FRAG 743) (SEQ. ID NO: 753) 55 5'- GA GGG CGG CAT GGC GGG CAC A-3' (FRAG 744) (SEQ. ID NO: 754) 5'- GA GGG CGG CAT GGC GGG CAC-3' (FRAG 745) (SEQ. ID NO: 755) 5'- GA GGG CGG CAT GGC GGG CA-3' (FRAG 746) (SEQ. ID NO: 756) 5'- GA GGG CGG CAT GGC GGG C-3' (FRAG 747) (SEQ. ID NO: 757) 5'- GA GGG CGG CAT GGC GGG -3' (FRAG 748) (SEQ. ID NO: 758) 60 5'- GA GGG CGG CAT GGC GG-3' (FRAG 749) (SEQ. ID NO: 759) 5'- GA GGG CGG CAT GGC G-3' (FRAG 750) (SEQ. ID NO: 760) 5'- GA GGG CGG CAT GGC -3' (FRAG 751) (SEQ. ID NO: 761) 5'- GA GGG CGG CAT GG -3' (FRAG 752) (SEQ. ID NO: 762) 5'- GA GGG CGG CAT G -3' (FRAG 753) (SEQ. ID NO: 763) 65 5'- GA GGG CGG CAT -3' (FRAG 754) (SEQ. ID NO: 764) 5'- GA GGG CGG CA-3' (FRAG 755) (SEQ. ID NO: 765) WO 00/62736 PCT/USOO/08020 118 5'- A GGG CGG CAT GGC GGG CAC AGG CTG GGC-3' (FRAG 756) (SEQ. ID NO: 766) 5'- A GGG CGG CAT GGC GGG CAC AGG CTG GG-3' (FRAG 757) (SEQ. ID NO: 767) 5'- A GGG CGG CAT GGC GGG CAC AGG CTG G-3' FRAGG 758) (SEQ. ID NO: 768) 5'- A GGG CGG CAT GGC GGG CAC AGG CTG -3' (FRAG 759) (SEQ. ID NO: 769) 5 5'- A GGG CGG CAT GGC GGG CAC AGG CT-3' (FRAG 760) (SEQ. ID NO: 770) 5'- A GGG CGG CAT GGC GGG CAC AGG C-3' (FRAG 761) (SEQ. ID NO: 771) 5'- A GGG CGG CAT GGC GGG CAC AGG -3' (FRAG 762) (SEQ. ID NO: 772) 5'- A GGG CGG CAT GGC GGG CAC AG-3' (FRAG 763) (SEQ. ID NO: 773) 5'- A GGG CGG CAT GGC GGG CAC A-3' (FRAG 764) (SEQ. ID NO: 774) 10 5'- A GGG CGG CAT GGC GGG CAC-3' (FRAG 765) (SEQ. ID NO: 775) 5'- A GGG CGG CAT GGC GGG CA-3' (FRAG 766) (SEQ. ID NO: 776) 5'- A GGG CGG CAT GGC GGG C-3' (FRAG 767) (SEQ. ID NO: 777) 5'- A GGG CGG CAT GGC GGG -3' (FRAG 768) (SEQ. ID NO: 778) 5'- A GGG CGG CAT GGC GG-3' (FRAG 769) (SEQ. ID NO: 779) 15 5'- A GGG CGG CAT GGC G-3' (FRAG 770) (SEQ. ID NO: 780) 5'- A GGG CGG CAT GGC -3' (FRAG 771) (SEQ. ID NO: 781) 5'- A GGG CGG CAT GG -3' (FRAG 772) (SEQ. ID NO: 782) 5'- A GGG CGG CAT G -3' (FRAG 773) (SEQ. ID NO: 783) 5'- A GGG CGG CAT -3' (FRAG 774) (SEQ. ID NO: 784) 20 5'- GGG CGG CAT GGC GGG CAC AGG CTG GGC-3' (FRAG 775) (SEQ. ID NO: 785) 5'- GGG CGG CAT GGC GGG CAC AGG CTG GG-3' (FRAG 776) (SEQ. ID NO: 786) 5'- GGG CGG CAT GGC GGG CAC AGG CTG G-3' (FRAG 777) (SEQ. ID NO: 787) 5'- GGG CGG CAT GGC GGG CAC AGG CTG -3' (FRAG 778) (SEQ. ID NO: 788) 5'- GGG CGG CAT GGC GGG CAC AGG CT-3' (FRAG 779) (SEQ. ID NO: 789) 25 5'- GGG CGG CAT GGC GGG CAC AGG C-3' (FRAG 780) (SEQ. ID NO: 790) 5'- GGG CGG CAT GGC GGG CAC AGG -3' (FRAG 781) (SEQ. ID NO: 791) 5'- GGG CGG CAT GGC GGG CAC AG-3' (FRAG 782) (SEQ. ID NO: 792) 5'- GGG CGG CAT GGC GGG CAC A-3' (FRAG 783) (SEQ. ID NO: 793) 5'- GGG CGG CAT GGC GGG CAC-3' (FRAG 784) (SEQ. ID NO: 794) 30 5'- GGG CGG CAT GGC GGG CA-3' (FRAG 785) (SEQ. ID NO: 795) 5'- GGG CGG CAT GGC GGG C-3' (FRAG 786) (SEQ. ID NO: 796) 5'- GGG CGG CAT GGC GGG -3' (FRAG 787) (SEQ. ID NO: 797) 5'- GGG CGG CAT GGC GG-3' (FRAG 788) (SEQ. ID NO: 798) 5'- GGG CGG CAT GGC G-3' (FRAG 789) (SEQ. ID NO: 799) 35 5'- GGG CGG CAT GGC -3' (FRAG 790) (SEQ. ID NO: 800) 5'- GGG CGG CAT GG -3' (FRAG 791) (SEQ. ID NO: 801) 5'- GGG CGG CAT G -3' (FRAG 792) (SEQ. ID NO: 802) 5'- GG CGG CAT GGC GGG CAC AG G CTG GGC-3' (FRAG 793) (SEQ. ID NO: 803) 5'- GG CGG CAT GGC GGG CAC AGG CTG GG-3' (FRAG 794) (SEQ. ID NO: 804) 40 5'- GG CGG CAT GGC GGG CAC AGG CTG G-3' (FRAG 795) (SEQ. ID NO: 805) 5'-' GG CGG CAT GGC GGG CAC AGG CTG -3' (FRAG 796) (SEQ. ID NO: 806) 5'- GG CGG CAT GGC GGG CAC AGG CT-3' (FRAG 797) (SEQ. ID NO: 807) 5'- GG CGG CAT GGC GGG CAC AGG C-3' (FRAG 798) (SEQ. ID NO: 808) 5'- GG CGG CAT GGC GGG CAC AGG -3' (FRAG 799) (SEQ. ID NO: 809) 45 5'- GG CGG CAT GGC GGG CAC AG-3' (FRAG 800) (SEQ. ID NO: 810) 5'- GG CGG CAT GGC GGG CAC A-3' (FRAG 801) (SEQ. ID NO: 811) 5'- GG CGG CAT GGC GGG CAC-3' (FRAG 802) (SEQ. ID NO: 812) 5'- GG CGG CAT GGC GGG CA-3' (FRAG 803) (SEQ. ID NO: 813) 5'- GG CGG CAT GGC GGG C-3' (FRAG 804) (SEQ. ID NO: 814) 50 5'- GG CGG CAT GGC GGG -3' (FRAG 805) (SEQ. ID NO: 815) 5'- GG CGG CAT GGC GG-3' (FRAG 806) (SEQ. ID NO: 816) 5'- GG CGG CAT GGC G-3' (FRAG 807) (SEQ. ID NO: 817) 5'- GG CGG CAT GGC -3' (FRAG 808) (SEQ. ID NO: 818) 5'- GG CGG CAT GG -3' (FRAG 809) (SEQ. ID NO: 819) 55 5'- G CGG CAT GGC GGG CAC AGG CTG GGC-3' (FRAG 810) (SEQ. ID NO: 820) 5'- G CGG CAT GGC GGG CAC AGG CTG GG-3' (FRAG 811) (SEQ. ID NO: 821) 5'- G CGG CAT GGC GGG CAC AGG CTG G-3' (FRAG 812) (SEQ. ID NO: 822) 5'- G CGG CAT GGC GGG CAC AGG CTG -3' (FRAG 813) (SEQ. ID NO: 823) 5'- G CGG CAT GGC GGG CAC AGG CT-3' (FRAG 814) (SEQ. ID NO: 824) 60 5'- G CGG CAT GGC GGG CAC AGG C-3' (FRAG 815) (SEQ. ID NO: 825) 5'- G CGG CAT GGC GGG CAC AGG -3' (FRAG 816) (SEQ. ID NO: 826) 5'- G CGG CAT GGC GGG CAC AG-3' (FRAG 817) (SEQ. ID NO: 827) 5'- G CGG CAT GGC GGG CAC A-3' (FRAG 818) (SEQ. ID NO: 828) 5'- G CGG CAT GGC GGG CAC-3' (FRAG 819) (SEQ. ID NO: 829) 65 5'- G CGG CAT GGC GGG CA-3' (FRAG 820) (SEQ. ID NO: 830) 5'- G CGG CAT GGC GGG C-3' (FRAG 821) (SEQ. ID NO: 831) WO 00/62736 PCT/US00/08020 119 5'- G CGG CAT GGC GGG -3' (FRAG 822) (SEQ. ID NO: 832) 5'- G CGG CAT GGC GG-3' (FRAG 823) (SEQ. ID NO: 833) 5'- G CGG CAT GGC G-3' (FRAG 824) (SEQ. ID NO: 834) 5'- G CGG CAT GGC -3' (FRAG 825) (SEQ. ID NO: 835) 5 5'- CGG CAT GGC GGG CAC AGG CTG GGC-3' (FRAG 826) (SEQ. ID NO: 836) 5'- CGG CAT GGC GGG CAC AGG CTG GG-3' (FRAG 827) (SEQ. ID NO: 837) 5'- CGG CAT GGC GGG CAC AGG CTG G-3' (FRAG 828) (SEQ. ID NO: 838) 5'- CGG CAT GGC GGG CAC AGG CTG -3' (FRAG 829) (SEQ. ID NO: 839) 5'- CGG CAT GGC GGG CAC AGG CT-3' (FRAG 830) (SEQ. ID NO: 840) 10 5'- CGG CAT GGC GGG CAC AGG C-3' (FRAG 831) (SEQ. ID NO: 841) 5'- CGG CAT GGC GGG CAC AGG -3' (FRAG 832) (SEQ. ID NO: 842) 5'- CGG CAT GGC GGG CAC AG-3' (FRAG 833) (SEQ. ID NO: 843) 5'- CGG CAT GGC GGG CAC A-3' (FRAG 834) (SEQ. ID NO: 844) 5'- CGG CAT GGC GGG CAC-3' (FRAG 835) (SEQ. ID NO: 845) 15 5'- CGG CAT GGC GGG CA-3' (FRAG 836) (SEQ. ID NO: 846) 5'- CGG CAT GGC GGG C-3' (FRAG 837) (SEQ. ID NO: 847) 5'- CGG CAT GGC GGG -3' (FRAG 838) (SEQ. ID NO: 848) 5'- CGG CAT GGC GG-3' (FRAG 839) (SEQ. ID NO: 849) 5'- CGG CAT GGC G-3' (FRAG 840) (SEQ. ID NO: 850) 20 5'- GG CAT GGC GGG CAC AGG C TG GGC-3' (FRAG 841) (SEQ. ID NO: 851) 5'- GG CAT GGC GGG CAC AGG CTG GG-3' (FRAG 842) (SEQ. ID NO: 852) 5'- GG CAT GGC GGG CAC AGG CTG G-3' (FRAG 843) (SEQ. ID NO: 853) 5'- GG CAT GGC GGG CAC AGG CTG -3' (FRAG 844) (SEQ. ID NO: 854) 5'- GG CAT GGC GGG CAC AGG CT-3' (FRAG 845) (SEQ. ID NO: 855) 25 5'- GG CAT GGC GGG CAC AGG C-3' (FRAG 846) (SEQ. ID NO: 856) 5'- GG CAT GGC GGG CAC AGG -3' (FRAG 847) (SEQ. ID NO: 857) 5'- GG CAT GGC GGG CAC AG-3' (FRAG 848) (SEQ. ID NO: 858) 5'- GG CAT GGC GGG CAC A-3' (FRAG 849) (SEQ. ID NO: 859) 5'- GG CAT GGC GGG CAC-3' (FRAG 850) (SEQ. ID NO: 860) 30 5'- GG CAT GGC GGG CA-3' (FRAG 851) (SEQ. ID NO: 861) 5'- GG CAT GGC GGG C-3' (FRAG 852) (SEQ. ID NO: 862) 5'- GG CAT GGC GGG -3' (FRAG 853) (SEQ. ID NO: 863) 5'- GG CAT GGC GG-3' (FRAG 854) (SEQ. ID NO: 864) 5'- G CAT GGC GGG CAC AGG CTG GGC-3' (FRAG 855) (SEQ. ID NO: 865) 35 5'- G CAT GGC GGG CAC AGG CTG GG-3' (FRAG 856) (SEQ. ID NO: 866) 5'- G CAT GGC GGG CAC AGG CTG G-3' (FRAG 857) (SEQ. ID NO: 867) 5'- G CAT GGC GGG CAC AGG CTG -3' (FRAG 858) (SEQ. ID NO: 868) 5'- G CAT GGC GGG CAC AGG CT-3' (FRAG 859) (SEQ. ID NO: 869) 5'- G CAT GGC GGG CAC AGG C-3' (FRAG 860) (SEQ. ID NO: 870) 40 5'- G CAT GGC GGG CAC AGG -3' (FRAG 861) (SEQ. ID NO: 871) 5'- G CAT GGC GGG CAC AG-3' (FRAG 862) (SEQ. ID NO: 872) 5'- G CAT GGC GGG CAC A-3' (FRAG 863) (SEQ. ID NO: 873) 5'- G CAT GGC GGG CAC-3' (FRAG 864) (SEQ. ID NO: 874) 5'- G CAT GGC GGG CA-3' (FRAG 865) (SEQ. ID NO: 875) 45 5'- G CAT GGC GGG C-3' (FRAG 866) (SEQ. ID NO: 876) 5'- G CAT GGC GGG -3' (FRAG 867) (SEQ. ID NO: 877) 5'- CAT GGC GGG CAC AGG CTG GGC-3' (FRAG 868) (SEQ. ID NO: 878) 5'- CAT GGC GGG CAC AGG CTG GG-3' (FRAG 869) (SEQ. ID NO: 879) 5'- CAT GGC GGG CAC AGG CTG G-3' (FRAG 870) (SEQ. ID NO: 880) 50 5'- CAT GGC GGG CAC AGG CTG -3' (FRAG 871) (SEQ. ID NO: 881) 5'- CAT GGC GGG CAC AGG CT-3' (FRAG 872) (SEQ. ID NO: 882) 5'- CAT GGC GGG CAC AGG C-3' (FRAG 873) (SEQ. ID NO: 883) 5'- CAT GGC GGG CAC AGG -3' (FRAG 874) (SEQ. ID NO: 884) 5'- CAT GGC GGG CAC AG-3' (FRAG 875) (SEQ. ID NO: 885) 55 5'- CAT GGC GGG CAC A-3' (FRAG 876) (SEQ. ID NO: 886) 5'- CAT GGC GGG CAC-3' (FRAG 877) (SEQ. ID NO: 887) 5'- CAT GGC GGG CA-3' (FRAG 878) (SEQ. ID NO: 888) 5'- CAT GGC GGG C-3' (FRAG 879) (SEQ. ID NO: 889) 5'- AT GGC GGG CAC AGG CTG GGC-3' (FRAG 880) (SEQ. ID NO: 890) 60 5'- AT GGC GGG CAC AGG CTG GG-3' FRAGG 881) (SEQ. ID NO: 891) 5'- AT GGC GGG CAC AGG CTG G-3' (FRAG 882) (SEQ. ID NO: 892) 5'- AT GGC GGG CAC AGG CTG -3' (FRAG 883) (SEQ. ID NO: 893) 5'- AT GGC GGG CAC AGG CT-3' (FRAG 884) (SEQ. ID NO: 894) 5'- AT GGC GGG CAC AGG C-3' (FRAG 885) (SEQ. ID NO: 895) 65 5'- AT GGC GGG CAC AGG -3' (FRAG 886) (SEQ. ID NO: 896) 5'- AT GGC GGG CAC AG-3' (FRAG 887) (SEQ. ID NO: 897) WO 00/62736 PCT/USOO/08020 120 5'- AT GGC GGG CAC A-3' (FRAG 888) (SEQ. ID NO: 898) 5'- AT GGC GGG CAC-3' (FRAG 889) (SEQ. ID NO: 899) 5'- AT GGC GGG CA-3' (FRAG 890) (SEQ. ID NO: 900) 5'- T GGC GGG CAC AGG CTG GGC-3' (FRAG 891) (SEQ. ID NO: 901) 5 5'- T GGC GGG CAC AGG CTG GG-3' (FRAG 892) (SEQ. ID NO: 902) 5'- T GGC GGG CAC AGG CTG G-3' (FRAG 893) (SEQ. ID NO: 903) 5'- T GGC GGG CAC AGG CTG -3' (FRAG 894) (SEQ. ID NO: 904) 5'- T GGC GGG CAC AGG CT-3' (FRAG 895) (SEQ. ID NO: 905) 5'- T GGC GGG CAC AGG C-3' (FRAG 896) (SEQ. ID NO: 906) 10 5'- T GGC GGG CAC AGG -3' (FRAG 897) (SEQ. ID NO: 907) 5'- T GGC GGG CAC AG-3' (FRAG 898) (SEQ. ID NO: 908) 5'- T GGC GGG CAC A-3' (FRAG 899) (SEQ. ID NO: 909) 5'- T GGC GGG CAC-3' (FRAG 900) (SEQ. ID NO: 910) 5'- GGC GGG CAC AGG CTG GGC-3' (FRAG 901) (SEQ. ID NO: 911) 15 5'- GGC GGG CAC AGG CTG GG-3' (FRAG 902) (SEQ. ID NO: 912) 5'- GGC GGG CAC AGG CTG G-3' (FRAG 903) (SEQ. ID NO: 913) 5'- GGC GGG CAC AGG CTG -3' (FRAG 904) (SEQ. ID NO: 914) 5'- GGC GGG CAC AGG CT-3' (FRAG 905) (SEQ. ID NO: 915) 5'- GGC GGG CAC AGG C-3' (FRAG 906) (SEQ. ID NO: 916) 20 5'- GGC GGG CAC AGG -3' (FRAG 907) (SEQ. ID NO: 917) 5'- GGC GGG CAC AG-3' (FRAG 908) (SEQ. ID NO: 918) 5'- GGC GGG CAC A-3' (FRAG 909) (SEQ. ID NO: 919) 5'- GC GGG CAC AGG CTG GGC-3' (FRAG 910) (SEQ. ID NO: 920) 5'- GC GGG CAC AGG CTG GG-3' (FRAG 911) (SEQ. ID NO: 921) 25 5'- GC GGG CAC AGG CTG G-3' (FRAG 912) (SEQ. ID NO: 922) 5'- GC GGG CAC AGG CTG -3' (FRAG 913) (SEQ. ID NO: 923) 5'- GC GGG CAC AGG CT-3' (FRAG 914) (SEQ. ID NO: 924) 5'- GC GGG CAC AGG C-3' (FRAG 915) (SEQ. ID NO: 925) 5'- GC GGG CAC AGG -3' (FRAG 916) (SEQ. ID NO: 926) 30 5'- GC GGG CAC AG-3' (FRAG 917) (SEQ. ID NO: 927) 5'- C GGG CAC AGG CTG GGC-3' (FRAG 918) (SEQ. ID NO: 928) 5'- GGG CAC AGG CTG GG-3' (FRAG 919) (SEQ. ID NO: 929) 5'- C GGG CAC AGG CTG G-3' (FRAG 920) (SEQ. ID NO: 930) 5'- C GGG CAC AGG CTG -3' (FRAG 921) (SEQ. ID NO: 931) 35 5'- C GGG CAC AGG CT-3' (FRAG 922) (SEQ. ID NO: 932) 5'- C GGG CAC AGG C-3' (FRAG 923) (SEQ. ID NO: 933) 5'- C GGG CAC AGG -3' (FRAG 924) (SEQ. ID NO: 934) 5'- GGG CAC AGG CTG GGC-3' (FRAG 925) (SEQ. ID NO: 935) 5'- GGG CAC AGG CTG GG-3' (FRAG 926) (SEQ. ID NO: 936) 40 5'- GGG CAC AGG CTG G-3' (FRAG 927) (SEQ. ID NO: 937) 5'- GGG CAC AGG CTG -3' (FRAG 928) (SEQ. ID NO: 938) 5'- GGG CAC AGG CT-3' (FRAG 929) (SEQ. ID NO: 939) 5'- GGG CAC AGG C-3' (FRAG 930) (SEQ. ID NO: 940) 5'- GG CAC AGG CTG GGC-3' (FRAG 931) (SEQ. ID NO: 941) 45 5'- GG CAC AGG CTG GG-3' (FRAG 932) (SEQ. ID NO: 942) 5'- GG CAC AGG CTG G-3' (FRAG 933) (SEQ. ID NO: 943) 5'-GG CAC AGG CTG -3' (FRAG 934) (SEQ. ID NO: 944) 5'- GG CAC AGG CT-3' (FRAG 935) (SEQ. ID NO: 945) 5'-G CAC AGG CTG GGC-3' (FRAG 936) (SEQ. ID NO: 946) 50 5'-G CAC AGG CTG GG-3' (FRAG 937) (SEQ. ID NO: 947) 5'-G CAC AGG CTG G-3' (FRAG 938) (SEQ. ID NO: 948) 5'-G CAC AGG CTG -3' (FRAG 939) (SEQ. ID NO: 949) 5'-CAC AGG CTG GGC-3' (FRAG 940) (SEQ. ID NO: 950) 5'-CAC AGG CTG GG-3' (FRAG 941) (SEQ. ID NO: 951) 55 5'-CAC AGG CTG G-3' (FRAG 942) (SEQ. ID NO: 952) 5'-AC AGG CTG GGC-3' (FRAG 943) (SEQ. ID NO: 953) 5'-AC AGG CTG GG-3' (FRAG 944) (SEQ. ID NO: 954) 5'-C AGG CTG GGC-3' (FRAG 945) (SEQ. ID NO: 955) 5'-TTT TCC TTC CTT TGT CTC TCT TC (FRAG 946) (SEQ. ID NO: 956) 60 5'-GCT CCC GGC TGC CTG (FRAG 947) (SEQ. ID NO: 957) 5'-CTC GGC CGT GCG GCT CTG TCG CTC CCG GT (FRAG 948) (SEQ. ID NO: 958) 5'-CCG CCG CCC TCC GGG GGG TC (FRAG 949) (SEQ. ID NO: 959) 5'-TGC TGC CGT TGG CTG CCC (FRAG 950) (SEQ. ID NO: 960) 5'-CTT CTG CGG GTC GCC GG (FRAG 951) (SEQ. ID NO: 961) 65 5'-TGC TGG GCT TGT GGC (FRAG 952) (SEQ. ID NO: 962) 5'-GGC CTC TCT TCT GGG (FRAG 953) (SEQ. ID NO: 963) WO 00/62736 PCT/USOO/08020 121 5'-CCT GGT CCC TCC GT (FRAG 954) (SEQ. ID NO: 964) 5'-GGT GGC TCC TCT GC (FRAG 955) (SEQ. ID NO: 965) 5'-GCT TGG TCC TGG GGC TGC (FRAG 956) (SEQ. ID NO: 966) 5'-TGC TCT CCT CTC CTT (FRAG 957) (SEQ. ID NO: 967) 5 Human Adenosine A2a Receptor Nucleic Acid and Antisense Oligonucleotide Fragments 5'-TGC TTT TCT TTT CTG GGC CTC TGT GGT CTG TTT TTT TCT G GCC CTG CTG GGG CGC TCT CC GCC GCC CGC CTG GCT CCC GGB GCC CBT GBT GGG CBT GCC GTG GTT CTT GCC CTC CTT TGG CTG CCG TGC CCG CTC CCC GGC CTC CTG GCG GGT GGC CGT TG GGC CCG TGT TCC CCT GGG -GCC TGG GGC TCC CTT CTC TC GCC CTT CTT GCT GGG CCT C TGC TGC TGC TGG TGC TGT GGC CCC C GTA CAC CGA GGA GCC 10 CAT GAT GGG CAT GCC ACA GAC GAC AGG C GTB CBC CGB GGB GCC CBT GBT GGG CBT GCC BCB GBC GBC BGG C-3' (FRAG. NO. 1665) (SEQ. ID NO:1680) 5'-CTG GGC CTC-3' (FRAG 1666) (SEQ. ID NO: 1681) 5'-TGC TTT TCT TTT CTG GGC CTC-3' (FRAG 958) (SEQ. ID NO: 968) 5'-TGT GGT CTG TTT TTT TCT G-3' (FRAG 959) (SEQ. ID NO: 969) 15 5'-GCC CTG CTG GGG CGC TCT CC-3' (FRAG 960) (SEQ. ID NO: 970) 5'-GCC GCC CGC CTG GCT CCC-3' (FRAG 961) (SEQ. ID NO: 971) 5'-GGB GCC CBT GBT GGG CBT GCC-3' (FRAG 962) (SEQ. ID NO: 972) 5'-GTG GTT CTT GCC CTC CTT TGG CTG-3' (FRAG 963) (SEQ. ID NO: 973) 5'-CCG TGC CCG CTC CCC GGC-3' (FRAG 964) (SEQ. ID NO: 974) 20 5'-CTC CTG GCG GGT GGC CGT TG-3' (FRAG 965) (SEQ. ID NO: 975) 5'-GGC CCG TGT TCC CCT GGG-3' (FRAG 966) (SEQ. ID NO: 976) 5'-GCC TGG GGC TCC CTT CTC TC-3' (FRAG 967) (SEQ. ID NO: 977) 5'-GCC CTT CTT GCT GGG CCT C-3' (FRAG 968) (SEQ. ID NO: 978) 5'-TGC TGC TGC TGG TGC TGT GGC CCC C-3' (FRAG 969) (SEQ. ID NO: 979) 25 5'-GTACACCGAGGAGCCCATGATGGGCATGCCACAGACGACAGGC-3' (FRAG 970) (SEQ. ID NO: 980) 5'-GTBCBCCGBGGBGCCCBTGBTGGGCBTGCCBCBGBCGBCBGGC-3' (FRAG 971) (SEQ. ID NO: 981) Human Adenosine A2b Receptor Nucleic Acid & Antisense Oligonucleotide Fragments 5'-GGC GCC GTG CCG CGT CTT GGT GGC GG GG GTT CGC GCC CGC GCG GGG CCC CTC CGG TCC GTT CGC GCC CGC GCG GGG CCC CTC CGG TCC CGG GTC GGG GCC CCC CGC GGC C GCC TCG GGG CTG GGG 30 CGC TGG TGG CCG GG CCG CGC CTC CGC CTG CCG CTT CTG GCT GGG CCC CGG GCG CCC CCT CCC CTC TTG CTC GGG TCC CCG TG ACA GCG CGT CCT GTG TCT CCA GCA GCA TGG CCG GGC CAG CTG GGC CCC BCB GCG CGT CCT GTG TCT CCB GCB GCB TGG CCG GGC CBG CTG GGC CCC CCCAGCCCCG AGGCTCAGAA GCGGCAGGCG GAGGCGCGGT CCGGGCGCTA TGGCCATGCC CGGCGGGTCT CACGCGGCTG CCCCTCGCCC GGCGCGCCTT CGGTAGGGGG CGCCCGGGGC CCAGCTGGCC CGGCCATGCT GCTGGAGACA 35 CAGGACGCGC TGTACGTGGC GCTGGAGCTG GTCATCGCCG CGCTTTCGGT GGCGGGCAAC GTGCTGGTGT GCGCCGCGGT GGGCACGGCG AACACTCTGC AGACGCCCAC CAACTACTTC CTGGTGTCCC TGGCTGCGGC CGACGTGGCC GTGGGGCTCT TCGCCATCCC CTTTGCCATC ACCATCAGCC TGGGCTTCTG CACTGACTTC TACGGCTGCC TCTTCCTCGC CTGCTTCGTG CTGGTGCTCA CGCAGAGCTC CATCTTCAGC CTTCTGGCCG TGGCAGTCGA CAGATACCTG GCCATCTGTG TCCCGCTCAG GTATAAAAGT TTGGTCACGG GGACCCGAGC 40 AAGAGGGGTC ATTGCTGTCC TCTGGGTCCT TGCCTTTGGC ATCGGATTGA CTCCATTCCT GGGGTGGAAC AGTAAAGACA GTGCCACCAA CAACTGCACA GAACCCTGGG ATGGAACCAC GAATGAAAGC TGCTGCCTTG TGAAGTGTCT CTTTGAGAAT GTGGTCCCCA TGAGCTACAT GGTATATTTC AATTTCTTTG GGTGTGTTCT GCCCCCACTG CTTATAATGC TGGTGATCTA CATTAAGATC TTCCTGGTGG CCTGCAGGCA GCTTCAGCGC ACTGAGCTGA TGGACCACTC GAGGACCACC CTCCAGCGGG AGATCCATGC AGCCAAGTCA CTGGCCATGA 45 TTGTGGGGAT TTTTGCCCTG TGCTGGTTAC CTGTGCATGC TGTTAACTGT GTCACTCTTT TCCAGCCAGC TCAGGGTAAA AATAAGCCCA AGTGGGCAAT GAATATGGCC ATTCTTCTGT CACATGCCAA TTCAGTTGTC AATCCCATTG TCTATGCTTA CCGGAACCGA GAC!TTCCGCT ACACTTTTCA CAAAATTATC TCCAGGTATC TTCTCTGCCA AGCAGATGTC AAGAGTGGGA ATGGTCAGGC TGGGGTACAG CCTGCTCTCG GTOTGGGCCT ATGATCTAGG CTCTCGCCTC TTCCAGGAGA AGATACAAAT CCACAAGAAA CAAAGAGGAC ACGGCTGGTT 50 TTCATTGTGA AAGATAGCTA CACCTCACAA GGAAATGGAC TGCCTCTCTT GAGCACTTCC CTGGAGCTAC CACGTATCTA GCTAATATGT ATGTGTCAGT AGTAGCACCA AGGATTGACA AATATATTTA TGATCTATTC AGCTGCTTTT ACTGTGTGGA TTATGCCAAC AGCTTGAATG GATTrCTAACA GACTCTTTTG TTTTTAAAAG TCTGCCTTGT TTATGGTGGA AAATTACTGA AACTATTTTA CTGTGAAACA GTGTGAACTA TTATAATGCA AATACTTTTT AACTTAGAGG CAATGGAAAA ATAAAAGTTG ACTGTACTAA AAATGTATAC TTGTTGCCAG 55 GAAGGTGACC TCAAAAATTA AAAGTATAAT TATTCGGCCG GGCATGGTGG CTCACACCTG TAATTCCAGC ACTTTGGGAG GCCAAGGCAG GCGGATCACG AGGTCAGGAG TTCAAAACCA GCCTGTCCAA TATAGTG GGGCAATTTG TTAGTTATCC GCCGCCACCA AGACGCGGCA CGGCGCCTGG ACCGGAGGGG CCCCGCGCGG GCGCGAACTTr TGGGCTCGGG CGAGTGGGTG GTGCTCCGCC CAGCCCGAGA CGGGCGGGCG CGCGGGCCAA TGGGTGCCGC CTCTTGGCCG CGGGGGGCCC CGACCCGTGG GTCCCGGCCA CCAGCGCCCC AGCCCCGAGG 60 CTCAGAAGCG GCAGGCGGAG GCGCGGTCCG GGCGCTATGG CCATGCCCGG CGGGTCTCAC GCGGCTGCCC CTCGCCCGGC GCGCCTTCGG TAGGGGGCGC CCGGGGCCCA GCTGGCCCGG CCATGCTGCT GGAGACACAG WO 00/62736 PCT/US00/08020 122 GACGCGCTGT ACGTGGCGCT GGAGCTGGTC ATCGCCGCGC TTTCGGTGGC GGGCAACGTG CTGGTGTGCG CCGCGGTGGG CACGGCGAAC ACTCTGCAGA CGCCCACCAA CTACTTCCTG GTGTCCCTGG CTGCGGCCGA CGTGGCCGTG GGGCTCTTCG CCATCCCCTT TGCCATCACC ATCAGCCTGG GCTTCTGCAC TGACTTCTAC GGCTGCCTCT TCCTCGCCTG CTTCGTGCTG GTGCTCACGC AGAGCTCCAT CTrCAGCC'rr CTGGCCGTGG 5 CAGTCGACAG ATACCTGGCC ATCTGTGTCC CGCTCAGGTA TAAAAGTTTG GTCACGGGGA CCCGAGCAAG AGGGGTCA IT GCTGTCCTCT.GGGTCCTTGC CM~GGCATC GGATTGACTC CAT7CCTGGG GTGGAACAGT AAAGACAGTG CCACCAACAA CTGCACAGAA CCCTGGGATG GAACCACGAA TGAAAGCTGC TGCCTTGTGA. AGTGTCTC'IT TGAGAATGTG GTCCCCATGA. GCTACATGGT ATATTTCAAT TTCTTTGGGT GTGTTCTGCC CCCACTGC17 ATAATGCTGG TGATCTACAT TAAGATCT7C CTGGTGGCCT GCAGGCAGCT TCAGCGCACT 10 GAGCTGATGG ACCACTCGAG GACCACCCTC CAGCGGGAGA TCCATGCAGC CAAGTCACTG GCCATGATrG TGGGGATT TGCCCTGTGC TGGTTACCTG TGCATGCTGT TAACTGTGTC ACTC=r~CC AGCCAGCTCA GGGTAAAAAT AAGCCCAAGT GGGCAATGAA. TATGGCCATT CTTCTGTCAC ATGCCAATTC AG'rrGTCAAT CCCATTGTCT ATGC FTACCG GAACCGAGAC TTCCGCTACA CTITTCACAA. AAT1'ATCTCC AGGTATCTTC TCTGCCAAGC AGATGTCAAG AGTGGGAATG GTCAGGCTGG GGTACAGCCT GCTCTCGGTG TGGGCCTATG 15 ATCTAGGCTC TCGCCTCTTC CAGGAGAAGA. TACAAATCCA CAAGAAACAA AGAGGACACG GCTGGTITC ATTGTGAAAG ATAGCTACAC CTCACAAGGA AATGGACTGC CTCTC= GAG CACTTCCCTG GAGCTACCAC GTATCTAGCT AATATGTATG TGTCAGTAGT AGGCTCCAAG GATTGACAAA TATAMfATG ATCTA'ITCAG CTGCTTTTAC TGTGTGGATT1 ATGCCAACAG CTTGAATGGA TTCTAACAGA CTCT1TGTT 'ITTAAAAGTC TGCCTTGT ATGGTGGAAA ATTACTGAAA CTATTACT GTGAAACAGT GTGAACTATT ATAATGCAAA 20 TACTTMAA CTAGAGGCA ATGGAAAAAT AAAAGTTGAC TGTACTAAAA ATG CCCAGCCCCG AGGCTCAGAA GCGGCAGGCG GAGGCGCGGT CCGGGCGCTA TGGCCATGCC CGGCGGGTCT CACGCGGCTG CCCCTCGCCC GGCGCGCCTT CGGTAGGGGG CGCCCGGGGC CCAGCTGGCC CGGCCATGCT GCTGGAGACA CAGGACGCGC TGTACGTGGC GCTGGAGCTG GTCATCGCCG CGC'ITTCGGT GGCGGGCAAC GTGCTGGTGT GCGCCGCGGT GGGCACGGCG AACACTCTGC AGACGCCCAC CAACTACTI7C CTGGTGTCCC TGGCTGCGGC 25 CGACGTGGCC GTGGGGCTCT TCGCCATCCC CTTTGCCATC ACCATCAGCC TGGGCTTCTG CACTGACTTC TACGGCTGCC TCTrCCTCGC CTGCTrCGTG CTGGTGCTCA CGCAGAGCTC CATCTrCAGC CTTCTGGCCG TGGCAGTCGA CAGATACCTG GCCATCTGTG TCCCGCTCAG GTATAAAAGT ITGGTCACGG GGACCCGAGC AAGAGGGGTC ATTGCTGTCC TCTGGGTCCT TGCCTTTGGC ATCGGATTGA CTCCA'ITCCT GGGGTGGAAC AGTAAAGACA GTGCCACCAA CAACTGCACA GAACCCTGGG ATGGAACCAC GAATGAAAGC TGCTGCCTIFG 30 TGAAGTGTCT CTTTGAGAAT GTGGTCCCCA TGAGCTACAT GGTATA1TIC AATC TITG GGTGTGTTCT GCCCCCACTG CTTATAATGC TGGTGATCTA CATTAAGATC 'ITCCTGGTGG CCTGCAGGCA GCY~rCAGCGC ACTGAGCTGA TGGACCACTC GAGGACCACC CTCCAGCGGG AGATCCATGC AGCCAAGTCA CTGGCCATGA TTGTGGGGAT 'FTGCCCTG TGCTGGTTAC CTGTGCATGC TGTTAACTGT GTCACTCTr TCCAGCCAGC TCAGGGTAAA AATAAGCCCA AGTGGGCAAT GAATATGGCC AT[CI1CTGT CACATGCCAA TTCAGTTGTC 35 AATCCCATTG TCTATGCT11A CCGGAACCGA GACTrCCGCT ACAC'LI1CA CAAAATTATC TCCAGGTATC T'rCTCTGCCA AGCAGATGTC AAGAGTGGGA ATGGTCAGGC TGGGGTACAG CCTGCTCTCG GTGTGGGCCT ATGATCTAGG CTCTCGCCTC TTCCAGGAGA AGATACAAAT CCACAAGAAA CAAAGAGGAC ACGGCTGGTr TTCATTGTGA AAGATAGCTA CACCTCACAA GGAAATGGAC TGCCTCTCTT GAGCACTTCC CTGGAGCTAC CACGTATCTA GCTAATATGT ATGTGTCAGT AGTAGCACCA AGGA'ITGACA AATATA1TTA TGATCTATI7C 40 AGCTGCYJTT ACTGTGTGGA TTATGCCAAC AGCTTGAATG GATTCTAACA GACTCT1TG TITITAAAAG TCTGCCTTGT TTATGGTGGA AAATTACTGA AACTATTA CTGTGAAACA GTGTGAACTA 'I1ATAATGCA AATACTM AACTTAGAGG CAATGGAAAA ATAAAAGTrG ACTGTACTAA AAATGTATAC 'I-GTTGCCAG GAAGGTGACC TCAAAAATTA AAAGTATAAT TATI7CGGCCG GGCATGGTGG CTCACACCTG TAATrCCAGC ACTTrGGGAG GCCAAGGCAG GCGGATCACG AGGTCAGGAG TTCAAAACCA GCCTGTCCAA TATAGTG 45 GGGCANITTG TfAGTTATCC GCCGCCACCA AGACGCGGCA CGGCGCCTGG ACCGGAGGGG CCCCGCGCGG GCGCGAACTT TGGGCTCGGG CGAGTGGGTG GTGCTCCGCC CAGCCCGAGA CGGGCGGGCG CGCGGGCCAA TGGGTGCCGC CTCTTGGCCG CGGGGGGCCC CGACCCGTGG GTCCCGGCCA CCAGCGCCCC AGCCCCGAGG CTCAGAAGCG GCAGGCGGAG GCGCGGTCCG GGCGCTATGG CCATGCCCGG CGGGTCTCAC GCGGCTGCCC CTCGCCCGGC GCGCCTTCGG TAGGGGGCGC CCGGGGCCCA GCTGGCCCGG CCATGCTGCT GGAGACACAG 50 GACGCGCTGT ACGTGGCGCT GGAGCTGGTC ATCGCCGCGC 'ITCGGTGGC GGGCAA.CGTG CTGGTGTGCG CCGCGGTGGG CACGGCGAAC ACTCTGCAGA CGCCCACCAA CTACTTCCTG GTGTCCCTGG CTGCGGCCGA CGTGGCCGTG GGGCTC'ITCG CCATCCCCTT TGCCATCACC ATCAGCCTGG GCTTCTGCAC TGACTrCTAC GGCTGCCTCT TCCTCGCCTG CTTCGTGCTG GTGCTCACGC AGAGCTCCAT C'ITCAGCCIT CTGGCCGTGG CAGTCGACAG ATACCTGGCC ATCTGTGTCC CGCTCAGGTA TAAAAGTI1TG GTCACGGGGA CCCGAGCAAG 55 AGGGGTCATT GCTGTCCTCT GGGTC=TGC CI=GGCATC GGATTGACTC CATrCCTGGG GTGGAACAGT AAAGACAGTG CCACCAACAA CTGCACAGAA CCCTGGGATG GAACCACGAA TGAAAGCTGC TGCCTTGTGA AGTGTCTCTI' TGAGAATGTG GTCCCCATGA GCTACATGGT ATATTTCAAT TI7CT'ITGGGT GTGTTCTGCC CCCACTGCTI1 ATAATGCTGG TGATCTACAT TAAGATCT7C CTGGTGGCCT GCAGGCAGCT TCAGCGCACT GAGCTGATGG ACCACTCGAG GACCACCCTC CAGCGGGAGA TCCATGCAGC CAAGTCACTG GCCATGATrTG 60 TGGGGAThT' TGCCCTGTGC TGGTTACCTG TGCATGCTGT TAACTGTGTC ACTCYITCC AGCCAGCTCA GGGTAAAAAT AAGCCCAAGT GGGCAATGAA TATGGCCATT CTTCTGTCAC ATGCCAATTC AGTTGTCAAT CCCATTGTCT ATGCTTACCG GAACCGAGAC TTCCGCTACA CTTTTCACAA. AATT1ATCTCC AGGTATCTTC TCTGCCAAGC AGATGTCAAG AGTGGGAATG GTCAGGCTGG GGTACAGCCT GCTCTCGGTG TGGGCCTATG ATCTAGGCTC TCGCCTCTT1C CAGGAGAAGA TACAAATCCA CAAGAAACAA AGAGGACACG GCTGGTITTC WO 00/62736 PCT/USOO/08020 123 ATTGTGAAAG ATAGCTACAC CTCACAAGGA AATGGACTGC CTCTCTTGAG CACTTCCCTG GAGCTACCAC GTATCTAGCT AATATGTATG TGTCAGTAGT AGGCTCCAAG GATTGACAAA TATATTTATG ATCTATTCAG CTGCTTTTAC TGTGTGGATT ATGCCAACAG CTTGAATGGA TTCTAACAGA CTCT GTT TTTAAAAGTC TGCCTTGTTT ATGGTGGAAA ATTACTGAAA CTATTACT GTGAAACAGT GTGAACTATT ATAATGCAAA 5 TACTTAA CTTAGAGGCA ATGGAAAAAT AAAAGTTGAC TGTACTAAAA ATG -3' (FRAG. NO: 1670) (SEQ. ID NO:3006) 5'- GGGCAATTTG TTAGTTATCC GCCGCCACCA AGACGCGGCA CGGCGCCTGG ACCGGAGGGG CCCCGCGCGG GCGCGAACTT TGGGCTCGGG CGAGTGGGTG GTGCTCCGCC CAGCCCGAGA CGGGCGGGCG CGCGGGCCAA TGGGTGCCGC CTCTTGGCCG CGGGGGGCCC CGACCCGTGG GTCCCGGCCA CCAGCGCCCC AGCCCCGAGG 10 CTCAGAAGCG GCAGGCGGAG GCGCGGTCCG GGCGCTATGG CCATGCCCGG CGGGTCTCAC GCGGCTGCCC CTCGCCCGGC GCGCCTTCGG TAGGGGGCGC CCGGGGCCCA GCTGGCCCGG CCATGCTGCT GGAGACACAG GACGCGCTGT ACGTGGCGCT GGAGCTGGTC ATCGCCGCGC TTTCGGTGGC GGGCAACGTG CTGGTGTGCG CCGCGGTGGG CACGGCGAAC ACTCTGCAGA CGCCCACCAA CTACTTCCTG GTGTCCCTGG CTGCGGCCGA CGTGGCCGTG GGGCTCTTCG CCATCCCCTT TGCCATCACC ATCAGCCTGG GCTICTGCAC TGACTTCTAC 15 GGCTGCCTCT TCCTCGCCTG CTTCGTGCTG GTGCTCACGC AGAGCTCCAT CTTCAGCCTT CTGGCCGTGG CAGTCGACAG ATACCTGGCC ATCTGTGTCC CGCTCAGGTA TAAAAGTTTG GTCACGGGGA CCCGAGCAAG AGGGGTCATT GCTGTCCTCT GGGTCCTTGC CTTTGGCATC GGATTGACTC CATTCCTGGG GTGGAACAGT AAAGACAGTG CCACCAACAA CTGCACAGAA CCCTGGGATG GAACCACGAA TGAAAGCTGC TGCCTTGTGA AGTGTCTCTT TGAGAATGTG GTCCCCATGA GCTACATGGT ATATTTCAAT TTCTTTGGGT GTGTTCTGCC 20 CCCACTGCTT ATAATGCTGG TGATCTACAT TAAGATCTTC CTGGTGGCCT GCAGGCAGCT TCAGCGCACT GAGCTGATGG ACCACTCGAG GACCACCCTC CAGCGGGAGA TCCATGCAGC CAAGTCACTG GCCATGATTG TGGGGATTTT TGCCCTGTGC TGGTrACCTG TGCATGCTGT TAACTGTGTC ACTCTCC AGCCAGCTCA GGGTAAAAAT AAGCCCAAGT GGGCAATGAA TATGGCCATT CTTCTGTCAC ATGCCAATTC AGTTGTCAAT CCCATTGTCT ATGCTTACCG GAACCGAGAC TTCCGCTACA CTTTTCACAA AATTATCTCC AGGTATCTTC 25 TCTGCCAAGC AGATGTCAAG AGTGGGAATG GTCAGGCTGG GGTACAGCCT GCTCTCGGTG TGGGCCTATG ATCTAGGCTC TCGCCTCTTC CAGGAGAAGA TACAAATCCA CAAGAAACAA AGAGGACACG GCTGGTTTC ATTGTGAAAG ATAGCTACAC CTCACAAGGA AATGGACTGC CTCTCTTGAG CACTTCCCTG GAGCTACCAC GTATCTAGCT AATATGTATG TGTCAGTAGT AGGCTCCAAG GATTGACAAA TATATATG ATCTATTCAG CTGCTTAC TGTGTGGATT ATGCCAACAG CTTGAATGGA TTCTAACAGA CTCTTTTGTT TTTAAAAGTC 30 TGCCTTGTTT ATGGTGGAAA ATTACTGAAA CTATTACT GTGAAACAGT GTGAACTATT ATAATGCAAA TACTIT'AA CTTAGAGGCA ATGGAAAAAT AAAAGTTGAC TGTACTAAAA ATG-3'(FRAG.NO:_(SEQ.ID NO:2436) 5'-CCCAGCCCCG AGGCTCAGAA GCGGCAGGCG GAGGCGCGGT CCGGGCGCTA TGGCCATGCC CGGCGGGTCT CACGCGGCTG CCCCTCGCCC GGCGCGCCTT CGGTAGGGGG CGCCCGGGGC CCAGCTGGCC CGGCCATGCT GCTGGAGACA CAGGACGCGC TGTACGTGGC GCTGGAGCTG GTCATCGCCG CGCTTTCGGT GGCGGGCAAC 35 GTGCTGGTGT GCGCCGCGGT GGGCACGGCG AACACTCTGC AGACGCCCAC CAACTACTTC CTGGTGTCCC TGGCTGCGGC CGACGTGGCC GTGGGGCTCT TCGCCATCCC CTTTGCCATC ACCATCAGCC TGGGCTTCTG CACTGACTTC TACGGCTGCC TCTTCCTCGC CTGCTTCGTG CTGGTGCTCA CGCAGAGCTC CATCTTCAGC CT7CTGGCCG TGGCAGTCGA CAGATACCTG GCCATCTGTG TCCCGCTCAG GTATAAAAGT TTGGTCACGG GGACCCGAGC AAGAGGGGTC ATTGCTGTCC TCTGGGTCCT TGCCTTTGGC ATCGGATTGA CTCCATTCCT 40 GGGGTGGAAC AGTAAAGACA GTGCCACCAA CAACTGCACA GAACCCTGGG ATGGAACCAC GAATGAAAGC TGCTGCCTTG TGAAGTGTCT CTGAGAAT GTGGTCCCCA TGAGCTACAT GGTATATTTC AATTTCTTTG GGTGTGTTCT GCCCCCACTG CT7ATAATGC TGGTGATCTA CATTAAGATC TTCCTGGTGG CCTGCAGGCA GCTTCAGCGC ACTGAGCTGA TGGACCACTC GAGGACCACC CTCCAGCGGG AGATCCATGC AGCCAAGTCA CTGGCCATGA TTGTGGGGAT TTTTGCCCTG TGCTGGTTAC CTGTGCATGC TGTTAACTGT GTCACTCTTIT 45 TCCAGCCAGC TCAGGGTAAA AATAAGCCCA AGTGGGCAAT GAATATGGCC ATTCTTCTGT CACATGCCAA TTCAGTTGTC AATCCCATTG TCTATGCTTA CCGGAACCGA GACTTCCGCT ACACTTTTCA CAAAATTATC TCCAGGTATC TTCTCTGCCA AGCAGATGTC AAGAGTGGGA ATGGTCAGGC TGGGGTACAG CCTGCTCTCG GTGTGGGCCT ATGATCTAGG CTCTCGCCTC TTCCAGGAGA AGATACAAAT CCACAAGAAA CAAAGAGGAC ACGGCTGGTT TTCATTGTGA AAGATAGCTA CACCTCACAA GGAAATGGAC TGCCTCTCTT GAGCACTTCC 50 CTGGAGCTAC CACGTATCTA GCTAATATGT ATGTGTCAGT AGTAGCACCA AGGATTGACA AATATATTTA TGATCTATTC AGCTGCTTTT ACTGTGTGGA TTATGCCAAC AGCTTGAATG GATTCTAACA GACTCTTG TTTAAAAG TCTGCCTTGT TTATGGTGGA AAATTACTGA AACTATTTTA CTGTGAAACA GTGTGAACTA TTATAATGCA AATACTTTTT AACTTAGAGG CAATGGAAAA ATAAAAGTTG ACTGTACTAA AAATGTATAC TTGTTGCCAG GAAGGTGACC TCAAAAATFA AAAGTATAAT TATTCGGCCG GGCATGGTGG CTCACACCTG 55 TAATTCCAGC ACTTTGGGAG GCCAAGGCAG GCGGATCACG AGGTCAGGAG TTCAAAACCA GCCTGTCCAA TATAGTG -3' FRAGG. NO:_) (SEQ. ID NO:2435) 5'- GGGCAATTTG TTAGTTATCC GCCGCCACCA AGACGCGGCA CGGCGCCTGG ACCGGAGGGG CCCCGCGCGG GCGCGAACTT TGGGCTCGGG CGAGTGGGTG GTGCTCCGCC CAGCCCGAGA CGGGCGGGCG CGCGGGCCAA TGGGTGCCGC CTCTTGGCCG CGGGGGGCCC CGACCCGTGG GTCCCGGCCA CCAGCGCCCC AGCCCCGAGG 60 CTCAGAAGCG GCAGGCGGAG GCGCGGTCCG GGCGCTATGG CCATGCCCGG CGGGTCTCAC GCGGCTGCCC CTCGCCCGGC GCGCCTTCGG TAGGGGGCGC CCGGGGCCCA GCTGGCCCGG CCATGCTGCT GGAGACACAG GACGCGCTGT ACGTGGCGCT GGAGCTGGTC ATCGCCGCGC TTTCGGTGGC GGGCAACGTG CTGGTGTGCG CCGCGGTGGG CACGGCGAAC ACTCTGCAGA CGCCCACCAA CTACTTCCTG GTGTCCCTGG CTGCGGCCGA CGTGGCCGTG GGGCTCTTCG CCATCCCCTT TGCCATCACC ATCAGCCTGG GCTTCTGCAC TGACTTCTAC WO 00/62736 PCT/US00/08020 124 GGCTGCCTCT TCCTCGCCTG CTTCGTGCTG GTGCTCACGC AGAGCTCCAT CTTCAGCCTT CTGGCCGTGG CAGTCGACAG ATACCTGGCC ATCTGTGTCC CGCTCAGGTA TAAAAGTTTG GTCACGGGGA CCCGAGCAAG AGGGGTCATT GCTGTCCTCT GGGTCCTTGC CTTTGGCATC GGATTGACTC CATTCCTGGG GTGGAACAGT AAAGACAGTG CCACCAACAA CTGCACAGAA CCCTGGGATG GAACCACGAA TGAAAGCTGC TGCCTTGTGA 5 AGTGTCTCTr TGAGAATGTG GTCCCCATGA GCTACATGGT ATATTTCAAT TTCTGGGT GTGTTCTGCC CCCACTGCTT ATAATGCTGG TGATCTACAT TAAGATCTTC CTGGTGGCCT GCAGGCAGCT TCAGCGCACT GAGCTGATGG ACCACTCGAG GACCACCCTC CAGCGGGAGA TCCATGCAGC CAAGTCACTG GCCATGATTG TGGGGATTTT TGCCCTGTGC TGGTTACCTG TGCATGCTGT TAACTGTGTC ACTCTTTTCC AGCCAGCTCA GGGTAAAAAT AAGCCCAAGT GGGCAATGAA TATGGCCATT CTTCTGTCAC ATGCCAATTC AGTTGTCAAT 10 CCCATTGTCT ATGCTTACCG GAACCGAGAC TTCCGCTACA CTTCACAA AATTATCTCC AGGTATCTTC TCTGCCAAGC AGATGTCAAG AGTGGGAATG GTCAGGCTGG GGTACAGCCT GCTCTCGGTG TGGGCCTATG ATCTAGGCTC TCGCCTCTTC CAGGAGAAGA TACAAATCCA CAAGAAACAA AGAGGACACG GCTGGTTTTC ATTGTGAAAG ATAGCTACAC CTCACAAGGA AATGGACTGC CTCTCTTGAG CACTTCCCTG GAGCTACCAC GTATCTAGCT AATATGTATG TGTCAGTAGT AGGCTCCAAG GATTGACAAA TATATTTATG ATCTATTCAG 15 CTGCTTTAC TGTGTGGATT ATGCCAACAG CTTGAATGGA TTCTAACAGA CTCTTTTGTT TTTAAAAGTC TGCCTTGTTT ATGGTGGAAA ATTACTGAAA CTATTTTACT GTGAAACAGT GTGAACTATT ATAATGCAAA TACTTTAA CTTAGAGGCA ATGGAAAAAT AAAAGTTGAC TGTACTAAAA ATG-3'(FRAG. NO:_)(SEQ.ID NO:2425) 5'-CCCAGCCCCG AGGCTCAGAA GCGGCAGGCG GAGGCGCGGT CCGGGCGCTA TGGCCATGCC CGGCGGGTCT CACGCGGCTG CCCCTCGCCC GGCGCGCCTT CGGTAGGGGG CGCCCGGGGC CCAGCTGGCC CGGCCATGCT 20 GCTGGAGACA CAGGACGCGC TGTACGTGGC GCTGGAGCTG GTCATCGCCG CGCTTTCGGT GGCGGGCAAC GTGCTGGTGT GCGCCGCGGT GGGCACGGCG AACACTCTGC AGACGCCCAC CAACTACrrC CTGGTGTCCC TGGCTGCGGC CGACGTGGCC GTGGGGCTCT TCGCCATCCC CTTTGCCATC ACCATCAGCC TGGGCTTCTG CACTGACTTC TACGGCTGCC TCTrCCTCGC CTGCTTCGTG CTGGTGCTCA CGCAGAGCTC CATCTTCAGC CTTCTGGCCG TGGCAGTCGA CAGATACCTG GCCATCTGTG TCCCGCTCAG GTATAAAAGT TTGGTCACGG 25 GGACCCGAGC AAGAGGGGTC ATTGCTGTCC TCTGGGTCCT TGCCTTGGC ATCGGATTGA CTCCATTCCT GGGGTGGAAC AGTAAAGACA GTGCCACCAA CAACTGCACA GAACCCTGGG ATGGAACCAC GAATGAAAGC TGCTGCCTTG TGAAGTGTCT CTTTGAGAAT GTGGTCCCCA TGAGCTACAT GGTATATC AATTCTTTG GGTGTGTTCT GCCCCCACTG CTTATAATGC TGGTGATCTA CATTAAGATC TTCCTGGTGG CCTGCAGGCA GCTTCAGCGC ACTGAGCTGA TGGACCACTC GAGGACCACC CTCCAGCGGG AGATCCATGC AGCCAAGTCA 30 CTGGCCATGA TTGTGGGGAT TTGCCCTG TGCTGGTTAC CTGTGCATGC TGTTAACTGT GTCACTCTTT TCCAGCCAGC TCAGGGTAAA AATAAGCCCA AGTGGGCAAT GAATATGGCC ATTCTTCTGT CACATGCCAA TTCAGTTGTC AATCCCATTG TCTATGCTTA CCGGAACCGA GACTTCCGCT ACACTTCA CAAAATTATC TCCAGGTATC TTCTCTGCCA AGCAGATGTC AAGAGTGGGA ATGGTCAGGC TGGGGTACAG CCTGCTCTCG GTGTGGGCCT ATGATCTAGG CTCTCGCCTC TTCCAGGAGA AGATACAAAT CCACAAGAAA CAAAGAGGAC 35 ACGGCTGGTT TTCATTGTGA AAGATAGCTA CACCTCACAA GGAAATGGAC TGCCTCTCTT GAGCACTTCC CTGGAGCTAC CACGTATCTA GCTAATATGT ATGTGTCAGT AGTAGCACCA AGGATTGACA AATATATTTA TGATCTATTC AGCTGCTT ACTGTGTGGA TTATGCCAAC AGCTTGAATG GATTCTAACA GACTCTTTTG TTTTAAAAG TCTGCCTTGT TTATGGTGGA AAATTACTGA AACTATTTTA CTGTGAAACA GTGTGAACTA TTATAATGCA AATACTTTT AACTTAGAGG CAATGGAAAA ATAAAAGTTG ACTGTACTAA AAATGTATAC 40 TTGTTGCCAG GAAGGTGACC TCAAAAATTA AAAGTATAAT TATTCGGCCG GGCATGGTGG CTCACACCTG TAATTCCAGC ACTTTGGGAG GCCAAGGCAG GCGGATCACG AGGTCAGGAG T7CAAAACCA GCCTGTCCAA TATAGTG (FRAG. NO: _) ( SEQ. ID NO: 2424) 5'-GCGCGTCCTG-3' (FRAG. NO: 1671) (SEQ. ID NO:1686) 5'-GCT GGG CCC CGG-3' (FRAG. NO: 1672) (SEQ. ID NO:1687) 45 5'-CGG GTC GGG GCC CCC C-3' (FRAG. NO: 1673) (SEQ. ID NO:1688) 5'- CGC GCC CGC G-3' (FRAG. NO: 1674) (SEQ. ID NO:1689) 5'-GGC GCC GTG CCG CGT CTT GGT GGC GGC GG-3' (FRAG 972) (SEQ. ID NO: 982) 5'-GTT CGC GCC CGC GCG GGG CCC CTC CGG TCC-3' (FRAG 973) (SEQ. ID NO: 983) 5'-GTT CGC GCC CGC GCG GGG CCC CTC CGG TCC-3' (FRAG 974) (SEQ. ID NO: 984) 50 5'-CGG GTC GGG GCC CCC CGC GGC C-3' (FRAG 975) (SEQ. ID NO: 985) 5'-GCC TCG GGG CTG GGG CGC TGG TGG CCG GG-3' (FRAG 976) (SEQ. ID NO: 986) 5'-CCG CGC CTC CGC CTG CCG CTT CTG-3' (FRAG 977) (SEQ. ID NO: 987) 5'-GCT GGG CCC CGG GCG CCC CCT-3' (FRAG 978) (SEQ. ID NO: 988) 5'-CCC CTC TTG CTC GGG TCC CCG TG-3' (FRAG 979) (SEQ. ID NO: 989) 55 5'-ACAGCGCGTCCTGTGTCTCCAGCAGCATGGCCGGGCCAGCTGGGCCCC-3' (FRAG 980) (SEQ. ID NO: 990) 5'-BCBGCGCGTCCTGTGTCTCCBGCBGCBTGGCCGGGCCBGCTGGGCCCC-3' (FRAG 981) (SEQ. ID NO: 991) Human Adenosine A3 Receptor Nucleic Acid and Antisense Oligonucleotide Fragments 5'-ACA GAG CAG TGC TGT TGT TGG GCA TCT TGC CTT CCC AGG G BCB GBG CB TGC TGT TGT TGG GCB TCT TGC CTT CCC BGG GCC CTT TTC TGG TGG GGT GOT GCT GTT GTT GGG CTT TCT TCT GTT CCC BCB 60 GBG CBG TGC TGT TGT TGG GCB TCT TGC CTT CCC BGG GCC CTT TTC TGG TGG GGT GOT GCT GTT GTT GGG C TTT CTT CTG TTC CC GAATTCCCAG ATGGGCAGAG GTGGCTGGGC TGGTGACCCT AAGTGTGTCT CCTGCCTTA TTCTCTCTAG TGGGTTATTC TTTCATGTGG TATCTTGCCT ACAGCATGCT GTGTTTGGAC ACAAACCCCT TrCCTTGGTT TCTCTGACCC AGCTGAGATG GACTGATTCC AAAAGAACTC ACCTATGTAC WO 00/62736 PCT/US00/08020 125 TGGGGTAGGG GAGGGAGGGT TT=GCAGT AMIAACTAA GGTTCAAAGA GTGCTATATA GTGAGAAAGG C'ITC'TTT TTTEFITT 'Tr=GGCA GAGTGCTGCC TCCTAGAAAT TTCTC'rrGGT AACTTCCTTrC TCTGAAGCAC AGATAAAGAA AACAATTACA GTAGAAACAT TTATGAGGGA CACAY]?GGAG GCCGATGAAG CTTrCAAGT TCCAGCAGTG CAGGGATGTG GGCAGAACTG ACATTGGAAA ATACTAGAAT GATGGAAA'T 5 CAGTTGGAGA GGACTciCCCT TTTTAATGTC TGGGGAGTCT GCTCAGGGAG AAATGACAAG TCTGGCGGGG ACAAGTATGG GA'TrTGGTAA GACTTGGATC AAC=GGGAT ACAGGGTGGG GGTCGGGAGT GGAATCAATG AATGATGCCA GAGCAGATCA ACTAACAAGA GGACCCTGAT GAGCCCCAGG CAGAGGCGTC TCCCT-FATGC CCCACTCTGA AGTGTTGrr AGTAAACACC AGAACGCCAT TGTrG'rrACT GCTGiAAYI A'TI17GGGCT GTACATATTT AGATGCTTAA GGTAAAAATG ATAAAGCCCT CAAGCCACTG TGTGGG'rrrG GGTCCAAGTG 10 TlCCTTCTTG CTGCCTCTCT AACACGCCTG GTTAAAATAA TcccTrGGA TGGTGCTGAG AAGCACCTGA ACCAAGTGGG TCCCCAAATA ACAATGGCGT GCAAGTGTCT GGI17CCCAGA AGT[GGTGAC TAGGTAAGCA GCTTCAGGGA GAGGGGGCTG ATTCCCAGAC AGTCGCCTGT TCCTGCGGGG ATGGGGCTGA GGCT~rGGGGA ATGTGGGCAG GAGGATATGC CATrTGATrC TGTrGCACAC G'FrCTTrCC CTTCTTTCTG TATGTCTGGT CATI'CTGCTA TTCTGTCGTr CCTCACATAG GTTGGACAfl GGCCGGCTGC CAGCATAAGT GCCAGTGTGA 15 TITTGCTAGG TGTGAGCTGA GAAAGAGAGG TGGAGGCTAA GCAGGTGTGA TGCTI7CTCAG AGGTGCTGAG T1TMGCCCT TCTGAGCAGG GAATCMIGC TTATCCCITFr GACCAAGGAT C1TTGCTGCA AAGGCTGGGT ATCGGCTGTG CTCAGCAAAG CGTCAACTCG TGCAAGAACT TAGCAGGAAT AGY-rCTGGCT AAGGTrAGGA GGCTGCCACC AAAGTCTCY[TT =GTTCCT CTGCTTCTCC CG ITTGCCTC C'ITATCATGA GATCTTTG CTAAGCTGGC AGAAAGATTG CATAGTCAGT GCTTCCAGCT CTGCTCCCAC CTGATCCTGC ACTGTCCTCT 20 GGTCCCTGAA TGAATGAACT CTGATACCCA ATC'rrGTCTC GAGCCTWFTC TATGCCACTC ATGGCTCCTC 'FrCTGCTCTT TCCATC'LTTT TGCTGAGAGT TCTGAGCTCT GTACTTCCTC 'YrGGCCCATC TCACTTCCTG AAACACCCCT GAAGAGGGTF GCTTATCTTG ATGGAACTCA AAAAGCCAAA AAGCTGCAGG CAGAGGCGTT GAGGACATCT GTTrGGGGAA CTAAGAGCAG CAGCAC'TrTC AGAITrCAGTC CATATAGAGC TGTCCTACAG CATTCTGGAA ACTTGAGGAT GTGCGGTGCA TAAAGGGGCT GGAAGTGACC CACCTGTGAT GAGCCC'I=C 25 TAAGGAGAAG GGTI1CCAAG AGATCACCCC ACCAGAAAAG GGTAGGAATG AGCAAGTrGG GAATTrAGA CTGTCACTGC ACATGGACCT CTGGGAAGAC GTCTGGCGAG AGCTAGGCCC ACTGGCCCTA CAGACGGATC T'rGCTGGCTC ACCTGTCCCT GTGGAGG ITC CCCTGGGAAG GCAAGATGCC CAACAACAGC ACTGCTCTGT CATTGGCCAA TGTTACCTAC ATCACCATGG AAATITCAT TGGACTCTGC GCCATAGTGG GCAACGTGGT GGTCATCTGC GTGGTCAAGC TGAACCCCAG CCTGCAGACC ACCACCTTCT AT11?CATTGT CTCTCTAGCC 30 CTGGCTGACA TJ7GCTG FrGG GGTGCTGGTC ATGCC'=GG ccATrGTTGT CAGCCTGGGC ATCACAATCC ACTTCTACAG CTGCCTTT ATGACTTGCC TACTGCTTAT C'rTrACCCAC GCCTCCATCA TGTCCTTGCT GGCCATCGCT GTGGACCGAT ACTTGCGGGT CAAGC'ITACC GTCAGGTAGC CTGCGGCGTG GGGTGGGCAG CAATTGAGGC AGCTGGGAAA TGAGGCTACA AAGCCAGAGC CTGCTGAAT' 'ITYIrrGGA CTGTACATAT TTrAGATGCTT AAGGTAAAAA TGATAAAGCC CTCAAGCCAC TGTGTGGGTT GGGTCCAAGT GTTCCTTGCT 35 GCTGCCTCTC TAACACGCCT GGTTAAAATA ATCC1MGG ATGGTGCTGA GAAGCACCTG AACCAAGTGG GTCCCCAAAT AACTATGGCG TGCAAGTGTC TGGTTCCCAG AAGTTGGTGA CTAGGTAAGC GACTCAGGGA GAGGGGCTGA TTCCCAGACA GTCGCCTG'Tr CCTGCTGGGA TGGGGCTGAG GCTrGGGGAA TGTGGGCAGG AGGATATGCC ATTTGATTCT G'ITGCACACG TrC'IICCC TrCTTrCTGT ATGTCTGGTC ATTrCTGCTAT TCTGTCGTTC CTCACATAGG TT1GGACA117G GCCGGCTGCC AGCATAAGTG CCAGTGTGAT TTGCTAGGG 40 TGTGAGCTGA GAAAGAGAGG TGGAGGCTAA GCAGGTGTGA TGCTrCTCAG AGGTGCTGAG TIT1GCCCT TCTGAGCAGG GAATC'TFTGC 'FrATCCC'IT GACCAAGGAT C'TGCTCCA AAGGCTGGGT ATCGGCTGTG CTCAGCAAAG CGTCAACTCG TGCAAGAACT TAGCAGGAAT AGTTCTGGCT AAGGTTAGGA GGCTGCCACC AAAGTCTCTI7 TITfGT-FCCT CTGCTrCTCC CG'ITGCCTC CTTATCATGA GATCT=~G CTAAGCTGGC AGAAAGATTG CATAATCAGT GC'rrCCAGCT CCGCTCCCAC CTGATCCTGC ACTGTCCTCT GGTCCCTGAA 45 TGAATGAACT CTGATACCCA ATCTTGTCTC GAGCCTCTC TATGCCACTC ATGGCTCCTC TTCTGCTCT-F TCCATCTPT TGCTGAGAGT TACTGAGCTC TGTACTTCCT CTTGGCCCAT CTCACTTCCT GAAACACCCC TGAAGAGGGT TGCTATCTT GATGGAACTC AAAAAGCCAA AAAGCTGCAG GCAGAGGCGT TGAGGACATC TGTITGGGGA ACTAAGAGCA GCAGCACTTT CAGAT7CAGT CCATATAGAG CTGTCCTACA GCAYI7CTGGA AACTTGAGGA TGTGCGGTGC ATAAAGGGGC TGGAAGTGAC CCACCTGTGA TGAGCCCTI CTAAGGAGAA 50 GGGYPTCCAA GAGATCACCC CACCAGAAAA GGGTAGGAAT GAGCAAGTTG GGAATITAG ACTGTCACTG CACATGGACC TCTGGGAAGA CGTCTGGCGA GAGCTAGGCC CACTGGCCCT ACAGACGGAT CTTGCTGGCT CACCTGTCCC TGTGGAGGTT CCCCTGGGAA GGCAAGATGC CCAACAACAG CACTGCTCTG CGAATTCGGG GGACATCTGT TTGGGGAACT AAGAGCAGCA GCACTrCAG ATT1CAGTCCA TATAGAGCTG TCCTACAGCA TI7CTGGAAAC TrGAGGATGT GCGGTGCATA AACGGGCTGG AAGTGACCCA CCTGTGATGA GCCCTI17CTA 55 AGGAGAAGGG TrCCAAGAG ATCACCCCAC CAGAAAAGGG TAGGAATGAG CAAGTTGGGA ATTI'AGACT GTCACTGCAC ATGGACCTCT GGGAAGACGT CTGGCGAGAG CTAGGCCCAC TGGCCCTACA GACGGATCTTF GCTGGCTCAC CTGTCCCTGT GGAGGTTCCC CTGGGAAGGC AAGATGCCCA ACAACAGCAC TGCTCTGTCA TTGGCCAATG TTACCTACAT CACCATGGAA A=CITrTG GACTCTGCGC CATAGTGGGC AACGTGCTGG TCATCTGCGT GGTCAAGCTG AACCCCAGCC TGCAGACCAC CACCTTCTAT TI7CATTGTCT CTCTAGCCCT 60 GGCTGACATT GCTGTTGGGG TGCTGGTCAT GCCTI1TGGCC ATTGTTGTCA GCCTGGGCAT CACAATCCAC T'rCTACAGCT GCCTI=AT GACTTGCCTA CTGCTTATCT TTACCCACGC CTCCATCATG TCCTrGCTGG CCATCGCTGT GGACCGATAC TTGCGGGTCA AGCTTACCGT CAGATACAAG AGGGTCACCA CTCACAGAAG AATATGGCTG GCCCTGGGCC TTFGCTGGCT GGTGTCATTC CTGGTGGGAT TGACCCCCAT G'I=GGCTGG AACATGAAAC TGACCTCAGA GTACCACAGA AATGTCACCT TCGInrCATG CCAA'TrGTT TCCGTCATGA WO 00/62736 PCT/USOO/08020 126 GGATGGACTA CATGGTATAC YI7CAGC'ITCC TCACCTGGAT TTrCATCCCC CTGGTrGTCA TGTGCGCCAT CTATC'ITGAC ATCI=IACA TCATTCGGAA CAAACTCAGT CTGAAC FIAT CTAACTCCAA AGAGACAGGT GCATTATG GACGGGAGTT CAAGACGGCT AAGTCC'TrGT TrCTGG'FCT =ITFrGMr GCTCTGTCAT GGCTGCCTTT ATCTCTCATC AACTGCATCA TCTAC'TrAA TGGTGAGGTA CCACAGCTTG TGCTGTACAT 5 GGGCATCCTG CTGTCCCATG CCAACTCCAT GATGAACCCT ATCGTCTATG CCTATAAAAT AAAGAAGT7C AAGGAAACCT ACCTTGAT CCTCAAAGCC TGTGTGGTCT GCCATCCCTC TGATTCTTTG GACACAAGCA YI7GAGAAGAA TrCTGAGTAG TTATCCATCA GAGATGACTC TGTCTCA'I17G ACCTI'CAGAT TCCCCATCAA CAAACACY'TG AGGGCCTGTA TGCCTGGGCC AAGGGAT1T TACATCCTTFG A'rrACTTCCA CTGAGGTGGG AGCATCTCCA GTGCTCCCCA ATFATATCTC CCCCACTCCA CTACTCTCTT CCTCCACTrC ATJTTCCTT 10 TGTCCITCT CTCTAATTCA GTG'TT1TGGA GGCCTGACTT GGGGACAACG TATFKI1?GAT ATTATTGTCT GTTTTCCFC TTCCCAATAG AAGAATAAGT CATGGAGCCT GAAGGGTGCC TAG'ITGACI17 ACTGACAAAA GGCTCTAGTT1 GGGCTGAACA TGTGTGTGGT GGTGACTCAT TTCCATGCCA TrGTGGAATr GAGCAGAGAA CCTGCTCTCG GAGGATGCCT AGGAGATGT GGGAACAGAA GAAATAAACT GAG'ITAAGG GGGACTTAAA CTGCTGAATT C GAATTCCCAG ATGGGCAGAG GTGGCTGGGC TGGTGACCCT AAGTGTGTCT CCTGCCTTTA 15 TTCTCTCTAG TGGGTTAYI7C T=CATGTGG TATCTTGCCT ACAGCATGCT GTGTTGGAC ACAAACCCCT TTCCTTGGTT TCTCTGACCC AGCTGAGATG GACTGATTCC AAAAGAACTC ACCTATGTAC TGGGGTAGGG GAGGGAGGGT ITTTTGCAGT A'TrAACTAA GGTTCAAAGA GTGCTATATA GTGAGAAAGG CTTCTTTTTr 'rrTTTrr TITITGGCA GAGTGCTGCC TCCTAGAAAT TTCTCTTGGT AACTTCCT7C TCTGAAGCAC AGATAAAGAA AACAAPTACA GTAGAAACAT TTATGAGGGA CACA I1GGAG GCCGATGAAG CT1TCAAGT 20 TCCAGCAGTG CAGGGATGTG GGCAGAACTG ACATI7GGAAA ATACTAGAAT GATGGAAATT CAGTTGGAGA GGACTGCCCT TrrAATGTC TGGGGAGTCT GCTCAGGGAG AAATGACAAG TCTGGCGGGG ACAAGTATGG GA=~GGTAA GACTTGGATC AACTTGGGAT ACAGGGTGGG GGTCGGGAGT GGAATCAATG AATGATGCCA GAGCAGATCA ACTAACAAGA GGACCCTGAT GAGCCCCAGG CAGAGGCGTC TCCCrrTATGC CCCACTCTGA AGTG ITGTT AGTAAACACC AGAACGCCAT TGTTGT17ACT GCTGAATIT ATITIGGGCT GTACATATT 25 AGATGC~rAA GGTAAAAATG ATAAAGCCCT CAAGCCACTG TGTGGGTG GGTCCAAGTG TTCCTTCTTG CTGCCTCTCT AACACGCCTG GTTAAAATAA TCCCTGGA TGGTGCTGAG AAGCACCTGA ACCAAGTGGG TCCCCAAATA ACAATGGCGT GCAAGTGTCT GGTTCCCAGA AGTTGGTGAC TAGGTAAG3CA GC'ITCAGGGA GAGGGGGCTG ATTCCCAGAC AGTCGCCTGT TCCTGCGGGG ATGGGGCTGA GGCTTGGGGA ATGTGGGCAG GAGGATATGC CA'rfGATrC TGTTGCACAC GTTCTITCC CTTC=TCTG TATGTCTGGT CATTCTGCTA 30 TTCTGTCGTT CCTCACATAG GTTGGACATI' GGCCGGCTGC CAGCATAAGT GCCAGTGTGA TT17FGCTAGG TGTGAGCTGA GAAAGAGAGG TGGAGGCTAA GCAGGTGTGA TGCTI1CTCAG AGGTGCTGAG 'ITTTTGCCCT TCTGAGCAGG GAATCTrGC FTATCCCTTT GACCAAGGAT CTTGCTGCA AAGGCTGGGT ATCGGCTGTG CTCAGCAAAG CGTCAACTCG TGCAAGAACT TAGCAGGAAT AGTT1CTGGCT AAGGTTAGGA GGCTGCCACC AAAGTCTCTT 'ITfrGTrCCT CTGCTFCTCC CGMflGCCTC CTTATCATGA GATCTI=G CTAAGCTGGC 35 AGAAAGATTG CATAGTCAGT GCTTCCAGCT CTGCTCCCAC CTGATCCTGC ACTGTCCTCT GGTCCCTGAA TGAATGAACT CTGATACCCA ATCTI'GTCTC GAGCCTTCTC TATGCCACTC ATGGCTCCTC ITCTGCTC= TCCATC'ITP TGCTGAGAGT TCTGAGCTCT GTACTT1CCTC TrGGCCCATC TCACTTCCTG AAACACCCCT GAAGAGGGTT GCTTATCTI'G ATGGAACTCA AAAAGCCAAA AAGCTGCAGG CAGAGGCG'T GAGGACATCT GTPrTGGGGAA CTAAGAGCAG CAGCACTfTC AGATTCAGTC CATATAGAGC TGTCCTACAG CATTFCTGGAA 40 ACTTGAGGAT GTGCGGTGCA TAAAGGGGCT GGAAGTGACC CACCTGTGAT GAGCCCTITC TAAGGAGAAG GG'TrTCCAAG AGATCACCCC ACCAGAAAAG GGTAGGAATG AGCAAGTTGG GAA'IrrAGA CTGTCACTGC ACATGGACCT CTGGGAAGAC GTCTGGCGAG AGCTAGGCCC ACTGGCCCTA CAGACGGATC TTGCTGGCTt ACCTGTCCCT GTGGAGGTT1C CCCTGGGAAG GCAAGATGCC CAACAACAGC ACTGCTCTGT CArrGGCCAA TGTTACCTAC ATCACCATGG AAATTfCAT TGGACTCTGC GCCATAGTGG GCAACGTGCT GGTCATCTGC 45 GTGGTCAAGC TGAACCCCAG CCTGCAGACC ACCACCTTCT A TTCATTGT CTCTCTAGCC CTGGCTGACA TTGCTGTTGG GGTGCTGGTC ATGCC'ITrGG CCATTGTTGT CAGCCTGGGC ATCACAATCC AC-FCTACAG CTGCC'ITTI ATGACTTGCC TACTGCTTAT CTI17ACCCAC GCCTCCATCA TGTCCTTGCT GGCCATCGCT GTGGACCGAT A=TGCGGGT CAAGCTTACC GTCAGGTAGC CTGCGGCGTG GGGTGGGCAG CAATrTGAGGC AGCTGGGAAA TGAGGCTACA AAGCCAGAGC CTGCTGAATT 'TATFGGA CTGTACATAT TTAGATGCTF 50 AAGGTAAAAA TGATAAAGCC CTCAAGCCAC TGTGTGGGT7 GGGTCCAAGT GTI7CCTrTGCT GCTGCCTCTC TAACACGCCT GGTTAAAATA ATCCCTTGG ATGGTGCTGA GAAGCACCTG AACCAAGTGG GTCCCCAAAT AACTATGGCG TGCAAGTGTC TGGTTCCCAG AAGTTGGTGA CTAGGTAAGC GACTCAGGGA GAGGGGCTGA YrCCCAGACA GTCGCCTGTT CCTGCTGGGA TGGGGCTGAG GCTFTGGGGAA TGTGGGCAGG AGGATATGCC ATrTGATTCT GTTGCACACG TTCTITCCC TrTTCTGT ATGTCTGGTC ATTCTGCTAT TCTGTCGTTC 55 CTCACATAGG TTGGACATTG GCCGGCTGCC AGCATAAGTG CCAGTGTGAT 'ITTGCTAGGG TGTGAGCTGA GAAAGAGAGG TGGAGGCTAA GCAGGTGTGA TGCTTCTCAG AGGTGCTGAG ITPTGCCCT TCTGAGCAGG GAATCTTTGC TTATCCCTTT GACCAAGGAT CITTGCTCCA AAGGCTGGGT ATCGGCTGTG CTCAGCAAAG CGTCAACTCG TGCAAGAACT TAGCAGGAAT AGTTCTGGCT AAGGTTAGGA GGCTGCCACC AAAGTCTCT7 T=rGTrCCT CTGCTTCTCC CGY11TGCCTC CTTrATCATGA GATCTTTG CTAAGCTGGC AGAAAGATITG 60 CATAATCAGT GCTTCCAGCT CCGCTCCCAC CTGATCCTGC ACTGTCCTCT GGTCCCTGAA TGAATGAACT CTGATACCCA ATCTTGTCTC GAGCCTTCTC TATGCCACTC ATGGCTCCTC 'FrCTGCTC'rT TCCATC1TTT TGCTGAGAGT TACTGAGCTC TGTACTTCCT CTT1GGCCCAT CTCAC'JTCCT GAAACACCCC TGAAGAGGGT TGCTTATCT4F GATGGAACTC AAAAAGCCAA AAAGCTGCAG GCAGAGGCGT TGAGGACATC TGTTTGGGGA ACTAAGAGCA GCAGCACTTT CAGATTCAGT CCATATAGAG CTGTCCTACA GCATTCTGGA AACTTGAGGA WO 00/62736 PCT/USOO/08020 127 TGTGCGGTGC ATAAAGGGGC TGGAAGTGAC CCACCTGTGA TGAGCCCTTT CTAAGGAGAA GGGTTTCCAA GAGATCACCC CACCAGAAAA GGGTAGGAAT GAGCAAGTTG GGAATTTTAG ACTGTCACTG CACATGGACC TCTGGGAAGA CGTCTGGCGA GAGCTAGGCC CACTGGCCCT ACAGACGGAT CTTGCTGGCT CACCTGTCCC TGTGGAGGTT CCCCTGGGAA GGCAAGATGC CCAACAACAG CACTGCTCTG CGAATTCGGG GGACATCTGT 5 TTGGGGAACT AAGAGCAGCA GCACTTTCAG ATTCAGTCCA TATAGAGCTG TCCTACAGCA TTCTGGAAAC TTGAGGATGT GCGGTGCATA AACGGGCTGG AAGTGACCCA CCTGTGATGA GCCCTTTCTA AGGAGAAGGG TTTCCAAGAG ATCACCCCAC CAGAAAAGGG TAGGAATGAG CAAGTTGGGA ATITTAGACT GTCACTGCAC ATGGACCTCT GGGAAGACGT CTGGCGAGAG CTAGGCCCAC TGGCCCTACA GACGGATCTT GCTGGCTCAC CTGTCCCTGT GGAGGTTCCC CTGGGAAGGC AAGATGCCCA ACAACAGCAC TGCTCTGTCA TTGGCCAATG 10 TTACCTACAT CACCATGGAA ATTrCATrG GACTCTGCGC CATAGTGGGC AACGTGCTGG TCATCTGCGT GGTCAAGCTG AACCCCAGCC TGCAGACCAC CACCTTCTAT TrCATTGTCT CTCTAGCCCT GGCTGACATT GCTGTTGGGG TGCTGGTCAT GCCTT'GGCC ATTGTTGTCA GCCTGGGCAT CACAATCCAC TTCTACAGCT GCCTTTAT GACTTGCCTA CTGCTTATCT TTACCCACGC CTCCATCATG TCCTTGCTGG CCATCGCTGT GGACCGATAC TTGCGGGTCA AGCTTACCGT CAGATACAAG AGGGTCACCA CTCACAGAAG AATATGGCTG 15 GCCCTGGGCC TTTGCTGGCT GGTGTCATTC CTGGTGGGAT TGACCCCCAT GT1GGCTGG AACATGAAAC TGACCTCAGA GTACCACAGA AATGTCACCT TCCTTTCATG CCAATTTGTT TCCGTCATGA GGATGGACTA CATGGTATAC TTCAGCTTCC TCACCTGGAT TTTCATCCCC CTGGTTGTCA TGTGCGCCAT CTATCTTGAC ATCTTTTACA TCATTCGGAA CAAACTCAGT CTGAACTTAT CTAACTCCAA AGAGACAGGT GCATTTTATG GACGGGAGTT CAAGACGGCT AAGTCCTTGT TTCTGGTTCT TTTCTrGTTT GCTCTGTCAT GGCTGCCT 20 ATCTCTCATC AACTGCATCA TCTACTAA TGGTGAGGTA CCACAGCTTG TGCTGTACAT GGGCATCCTG CTGTCCCATG CCAACTCCAT GATGAACCCT ATCGTCTATG CCTATAAAAT AAAGAAGTTC AAGGAAACCT ACCTTTTGAT CCTCAAAGCC TGTGTGGTCT GCCATCCCTC TGATrCTTTG GACACAAGCA TTGAGAAGAA TTCTGAGTAG TTATCCATCA GAGATGACTC TGTCTCATTG ACCTTCAGAT TCCCCATCAA CAAACACTTG AGGGCCTGTA TGCCTGGGCC AAGGGATTTT TACATCCTTG ATTACTTCCA CTGAGGTGGG AGCATCTCCA 25 GTGCTCCCCA ATTATATCTC CCCCACTCCA CTACTCTCTT CCTCCACTTC ATTTTTCCTT TGTCCTTTCT CTCTAATTCA GTGTITTGGA GGCCTGACTT GGGGACAACG TATTATTGAT ATTATTGTCT GTTTCCTTC TTCCCAATAG AAGAATAAGT CATGGAGCCT GAAGGGTGCC TAGTTGACTT ACTGACAAAA GGCTCTAGTT GGGCTGAACA TGTGTGTGGT GGTGACTCAT TTCCATGCCA TTGTGGAATT GAGCAGAGAA CCTGCTCTCG GAGGATGCCT AGGAGATGTT GGGAACAGAA GAAATAAACT GAGTAAGG GGGACTTAAA CTGCTGAATT C 30 -3' (FRAG. NO:1675) (SEQ. ID NO:3007) 5'- CGAATTCGGG GGACATCTGT TTGGGGAACT AAGAGCAGCA GCACTTCAG ATTCAGTCCA TATAGAGCTG TCCTACAGCA TTCTGGAAAC TTGAGGATGT GCGGTGCATA AACGGGCTGG AAGTGACCCA CCTGTGATGA GCCCTTTCTA AGGAGAAGGG TTTCCAAGAG ATCACCCCAC CAGAAAAGGG TAGGAATGAG CAAGTTGGGA ATTTTAGACT GTCACTGCAC ATGGACCTCT GGGAAGACGT CTGGCGAGAG CTAGGCCCAC TGGCCCTACA 35 GACGGATCTT GCTGGCTCAC CTGTCCCTGT GGAGGTTCCC CTGGGAAGGC AAGATGCCCA ACAACAGCAC TGCTCTGTCA TTGGCCAATG TTACCTACAT CACCATGGAA ATTTCATTG GACTCTGCGC CATAGTGGGC AACGTGCTGG TCATCTGCGT GGTCAAGCTG AACCCCAGCC TGCAGACCAC CACCTTCTAT TTCATTGTCT CTCTAGCCCT GGCTGACATT GCTGTTGGGG TGCTGGTCAT GCC'TTGGCC ATTGTTGTCA GCCTGGGCAT CACAATCCAC TTCTACAGCT GCCTTTAT GACTTGCCTA CTGCTTATCT TTACCCACGC CTCCATCATG 40 TCCTTGCTGG CCATCGCTGT GGACCGATAC TTGCGGGTCA AGCTTACCGT CAGATACAAG AGGGTCACCA CTCACAGAAG AATATGGCTG GCCCTGGGCC TTTGCTGGCT GGTGTCATTC CTGGTGGGAT TGACCCCCAT GTTTGGCTGG AACATGAAAC TGACCTCAGA GTACCACAGA AATGTCACCT TCCTTCATG CCAATTTGTT TCCGTCATGA GGATGGACTA CATGGTATAC TrCAGCTrCC TCACCTGGAT TTTCATCCCC CTGGTTGTCA TGTGCGCCAT CTATCTTGAC ATCTTTACA TCATTCGGAA CAAACTCAGT CTGAACTTAT CTAACTCCAA 45 AGAGACAGGT GCATTTATG GACGGGAGTT CAAGACGGCT AAGTCCTTGT TTCTGGTTCT TTTCTrGTTT GCTCTGTCAT GGCTGCCTT ATCTCTCATC AACTGCATCA TCTACTTTAA TGGTGAGGTA CCACAGCTTG TGCTGTACAT GGGCATCCTG CTGTCCCATG CCAACTCCAT GATGAACCCT ATCGTCTATG CCTATAAAAT AAAGAAGTTC AAGGAAACCT ACCTTGAT CCTCAAAGCC TGTGTGGTCT GCCATCCCTC TGATrCTTITrG GACACAAGCA TTGAGAAGAA TTCTGAGTAG TTATCCATCA GAGATGACTC TGTCTCATTG ACCTTCAGAT 50 TCCCCATCAA CAAACACTTG AGGGCCTGTA TGCCTGGGCC AAGGGATT TACATCCTTG ATTACTTCCA CTGAGGTGGG AGCATCTCCA GTGCTCCCCA ATTATATCTC CCCCACTCCA CTACTCTCTT CCTCCACTTC ATTTTCCTT TGTCCTCT CTCTAATTCA GTGTTTTGGA GGCCTGACTT GGGGACAACG TATTATTGAT ATTATTGTCT GTCCTTC TTCCCAATAG AAGAATAAGT CATGGAGCCT GAAGGGTGCC TAGTTGACTT ACTGACAAAA GGCTCTAGTT GGGCTGAACA TGTGTGTGGT GGTGACTCAT TTCCATGCCA TTGTGGAATT 55 GAGCAGAGAA CCTGCTCTCG GAGGATGCCT AGGAGATGTT GGGAACAGAA GAAATAAACT GAGTTAAGG GGGACTTAAA CTGCTGAATT C -3' (FRAG. NO:_) (SEQ. ID NO:2439) 5'- CTGCTGAATT TTATTTTGGA CTGTACATAT TTAGATGCTT AAGGTAAAAA TGATAAAGCC CTCAAGCCAC TGTGTGGGTT GGGTCCAAGT GTTCCTTGCT GCTGCCTCTC TAACACGCCT GGTT7AAAATA ATCCCTTTGG ATGGTGCTGA GAAGCACCTG AACCAAGTGG GTCCCCAAAT AACTATGGCG TGCAAGTGTC TGGTTCCCAG 60 AAGTTGGTGA CTAGGTAAGC GACTCAGGGA GAGGGGCTGA TTCCCAGACA GTCGCCTGTT CCTGCTGGGA TGGGGCTGAG GCTTGGGGAA TGTGGGCAGG AGGATATGCC ATTTGATTCT GTTGCACACG TTCTTTTCCC TTCTTTCTGT ATGTCTGGTC ATTCTGCTAT TCTGTCGTTC CTCACATAGG TTGGACATTG GCCGGCTGCC AGCATAAGTG CCAGTGTGAT TTTGCTAGGG TGTGAGCTGA GAAAGAGAGG TGGAGGCTAA GCAGGTGTGA TGCTTCTCAG AGGTGCTGAG TITTGCCCT TCTGAGCAGG GAATCTTTGC TTATCCCTT GACCAAGGAT WO 00/62736 PCT/USOO/08020 128 CTTTGCTCCA AAGGCTGGGT ATCGGCTGTG CTCAGCAAAG CGTCAACTCG TGCAAGAACT TAGCAGGAAT AGTTCTGGCT AAGGTTAGGA GGCTGCCACC AAAGTCTCTT TTGTrCCT CTGCTTCTCC CGTTTGCCTC CTTATCATGA GATCTTTTTG CTAAGCTGGC AGAAAGATTG CATAATCAGT GCTTCCAGCT CCGCTCCCAC CTGATCCTGC ACTGTCCTCT GGTCCCTGAA TGAATGAACT CTGATACCCA ATCTTGTCTC GAGCCTTCTC 5 TATGCCACTC ATGGCTCCTC TTrCTGCTCTT TCCATCTTTT TGCTGAGAGT TACTGAGCTC TGTACTTCCT CTTGGCCCAT CTCACTTCCT GAAACACCCC TGAAGAGGGT TGCTTATCTT GATGGAACTC AAAAAGCCAA AAAGCTGCAG GCAGAGGCGT TGAGGACATC TGTTGGGGA ACTAAGAGCA GCAGCACTTT CAGATTCAGT CCATATAGAG CTGTCCTACA GCATrCTGGA AACTTGAGGA TGTGCGGTGC ATAAAGGGGC TGGAAGTGAC CCACCTGTGA TGAGCCCTTT CTAAGGAGAA GGGTTTCCAA GAGATCACCC CACCAGAAAA GGGTAGGAAT 10 GAGCAAGTTG GGAATTTTAG ACTGTCACTG CACATGGACC TCTGGGAAGA CGTCTGGCGA GAGCTAGGCC CACTGGCCCT ACAGACGGAT CTTGCTGGCT CACCTGTCCC TGTGGAGGTT CCCCTGGGAA GGCAAGATGC CCAACAACAG CACTGCTCTG -3' (FRAG. NO:_) (SEQ. ID NO:2438) 5'- GAATTCCCAG ATGGGCAGAG GTGGCTGGGC TGGTGACCCT AAGTGTGTCT CCTGCCTTTA TTCTCTCTAG TGGGTTATTC TTTCATGTGG TATCTTGCCT ACAGCATGCT GTGTTTGGAC ACAAACCCCT TrCCTTGGTr 15 TCTCTGACCC AGCTGAGATG GACTGATTCC AAAAGAACTC ACCTATGTAC TGGGGTAGGG GAGGGAGGGT TTTTTGCAGT ATTTAACTAA GGTTCAAAGA GTGCTATATA GTGAGAAAGG CTTCTTTT TTTTTTTTTT TTTTTGGCA GAGTGCTGCC TCCTAGAAAT TTCTCTTGGT AACTTCCTTC TCTGAAGCAC AGATAAAGAA AACAATTACA GTAGAAACAT TTATGAGGGA CACATTGGAG GCCGATGAAG CTTCAAGT TCCAGCAGTG CAGGGATGTG GGCAGAACTG ACATTGGAAA ATACTAGAAT GATGGAAATT CAGTTGGAGA GGACTGCCCT 20 TTAATGTC TGGGGAGTCT GCTCAGGGAG AAATGACAAG TCTGGCGGGG ACAAGTATGG GATTTGGTAA GACTTGGATC AACTTGGGAT ACAGGGTGGG GGTCGGGAGT GGAATCAATG AATGATGCCA GAGCAGATCA ACTAACAAGA GGACCCTGAT GAGCCCCAGG CAGAGGCGTC TCCCTTATGC CCCACTCTGA AGTGTTTGTT AGTAAACACC AGAACGCCAT TGTTGTTACT GCTGAATT A1TTGGGCT GTACATAT AGATGCTTAA GGTAAAAATG ATAAAGCCCT CAAGCCACTG TGTGGGTTTG GGTCCAAGTG TTCCTTCTTG CTGCCTCTCT 25 AACACGCCTG GTTAAAATAA TCCCTTTGGA TGGTGCTGAG AAGCACCTGA ACCAAGTGGG TCCCCAAATA ACAATGGCGT GCAAGTGTCT GGTTCCCAGA AGTTGGTGAC TAGGTAAGCA GCTTCAGGGA GAGGGGGCTG ATTCCCAGAC AGTCGCCTGT TCCTGCGGGG ATGGGGCTGA GGCTTGGGGA ATGTGGGCAG GAGGATATGC CATTTGATTC TGTTGCACAC GTTC1TTCC CTTCTTTCTG TATGTCTGGT CATTCTGCTA TTCTGTCGTT CCTCACATAG GTTGGACATT GGCCGGCTGC CAGCATAAGT GCCAGTGTGA TTGCTAGG TGTGAGCTGA 30 GAAAGAGAGG TGGAGGCTAA GCAGGTGTGA TGCTTCTCAG AGGTGCTGAG TITGCCCT TCTGAGCAGG GAATCTTTGC TTATCCCTTT GACCAAGGAT CTTTGCTGCA AAGGCTGGGT ATCGGCTGTG CTCAGCAAAG CGTCAACTCG TGCAAGAACT TAGCAGGAAT AGTTCTGGCT AAGGTTAGGA GGCTGCCACC AAAGTCTCTT TTTTGT'CCT CTGCTTCTCC CGTGCCTC CTTATCATGA GATCTTTG CTAAGCTGGC AGAAAGATTG CATAGTCAGT GCTTCCAGCT CTGCTCCCAC CTGATCCTGC ACTGTCCTCT GGTCCCTGAA TGAATGAACT 35 CTGATACCCA ATCTTGTCTC GAGCCTrCTC TATGCCACTC ATGGCTCCTC TTCTGCTCTT TCCATCTTT TGCTGAGAGT TCTGAGCTCT GTACTTCCTC TTGGCCCATC TCACTTCCTG AAACACCCCT GAAGAGGGTT GCTTATCTTG ATGGAACTCA AAAAGCCAAA AAGCTGCAGG CAGAGGCGTT GAGGACATCT GTTTGGGGAA CTAAGAGCAG CAGCACTTTC AGATTCAGTC CATATAGAGC TGTCCTACAG CATTCTGGAA ACTTGAGGAT GTGCGGTGCA TAAAGGGGCT GGAAGTGACC CACCTGTGAT GAGCCCTTTC TAAGGAGAAG GGTTTCCAAG 40 AGATCACCCC ACCAGAAAAG GGTAGGAATG AGCAAGTTGG GAATTTTAGA CTGTCACTGC ACATGGACCT CTGGGAAGAC GTCTGGCGAG AGCTAGGCCC ACTGGCCCTA CAGACGGATC TTGCTGGCTC ACCTGTCCCT GTGGAGGTTC CCCTGGGAAG GCAAGATGCC CAACAACAGC ACTGCTCTGT CATTGGCCAA TGTTACCTAC ATCACCATGG AAATTCAT TGGACTCTGC GCCATAGTGG GCAACGTGCT GGTCATCTGC GTGGTCAAGC TGAACCCCAG CCTGCAGACC ACCACCTTCT ATTTCATTGT CTCTCTAGCC CTGGCTGACA TTGCTGTTGG 45 GGTGCTGGTC ATGCCTTTGG CCATTGTTGT CAGCCTGGGC ATCACAATCC ACTTCTACAG CTGCCTTTTT ATGACTTGCC TACTGCTTAT CTTTACCCAC GCCTCCATCA TGTCCTTGCT GGCCATCGCT GTGGACCGAT ACTTGCGGGT CAAGCTTACC GTCAGGTAGC CTGCGGCGTG GGGTGGGCAG CAATTGAGGC AGCTGGGAAA TGAGGCTACA AAGCCAGAGC -3' (FRAG. NO:_) (SEQ. ID NO:2437) 5'-CGAATTCGGG GGACATCTGT TTGGGGAACT AAGAGCAGCA GCACTTTCAG ATTCAGTCCA TATAGAGCTG 50 TCCTACAGCA TTCTGGAAAC TTGAGGATGT GCGGTGCATA AACGGGCTGG AAGTGACCCA CCTGTGATGA GCCCTTTCTA AGGAGAAGGG TTTCCAAGAG ATCACCCCAC CAGAAAAGGG TAGGAATGAG CAAGTTGGGA ATTTTAGACT GTCACTGCAC ATGGACCTCT GGGAAGACGT CTGGCGAGAG CTAGGCCCAC TGGCCCTACA GACGGATCTT GCTGGCTCAC CTGTCCCTGT GGAGGTTCCC CTGGGAAGGC AAGATGCCCA ACAACAGCAC TGCTCTGTCA TTGGCCAATG TTACCTACAT CACCATGGAA ATTTTCATTG GACTCTGCGC CATAGTGGGC 55 AACGTGCTGG TCATCTGCGT GGTCAAGCTG AACCCCAGCC TGCAGACCAC CACCTTCTAT TTCATTGTCT CTCTAGCCCT GGCTGACATT GCTGTTGGGG TGCTGGTCAT GCCTTTGGCC ATTGTTGTCA GCCTGGGCAT CACAATCCAC T7CTACAGCT GCCTTTAT GACTTGCCTA CTGCTTATCT TTACCCACGC CTCCATCATG TCCTTGCTGG CCATCGCTGT GGACCGATAC TTGCGGGTCA AGCTTACCGT CAGATACAAG AGGGTCACCA CTCACAGAAG AATATGGCTG GCCCTGGGCC TTTGCTGGCT GGTGTCATTC CTGGTGGGAT TGACCCCCAT 60 GTTTGGCTGG AACATGAAAC TGACCTCAGA GTACCACAGA AATGTCACCT TCCTTTCATG CCAATTTGTT TCCGTCATGA GGATGGACTA CATGGTATAC TTCAGCTTCC TCACCTGGAT TTTCATCCCC CTGGTTGTCA TGTGCGCCAT CTATCTTGAC ATCTITACA TCATTCGGAA CAAACTCAGT CTGAACTTAT CTAACTCCAA AGAGACAGGT GCATTATG GACGGGAGTT CAAGACGGCT AAGTCCTrGT TTCTGGTTCT TTTCTTGTTT GCTCTGTCAT GGCTGCCTTT ATCTCTCATC AACTGCATCA TCTACTTTAA TGGTGAGGTA CCACAGCTTG WO 00/62736 PCT/USOO/08020 129 TGCTGTACAT GGGCATCCTG CTGTCCCATG CCAACTCCAT GATGAACCCr ATCGTCTATG CCTATAAAAT AAAGAAGTTC AAGGAAACCT ACCTTTGAT CCTCAAAGCC TGTGTGGTCT GCCATCCCTC TGATTCTTTG GACACAAGCA TTGAGAAGAA TTCTGAGTAG TTATCCATCA GAGATGACTC TGTCTCATTG ACCTTCAGAT TCCCCATCAA CAAACACTTG AGGGCCTGTA TGCCTGGGCC AAGGGATTTT TACATCCTTG ATTACTTCCA 5 CTGAGGTGGG AGCATCTCCA GTGCTCCCCA ATTATATCTC CCCCACTCCA CTACTCTCTT CCTCCACTTC ATTTTTCCTT TGTCCTTTCT CTCTAATTCA GTGTTTGGA GGCCTGACTT GGGGACAACG TATTATTGAT ATTATTGTCT GTTTTCCTTC TTCCCAATAG AAGAATAAGT CATGGAGCCT GAAGGGTGCC TAGTTGACTT ACTGACAAAA GGCTCTAGTT GGGCTGAACA TGTGTGTGGT GGTGACTCAT TTCCATGCCA TTGTGGAATT GAGCAGAGAA CCTGCTCTCG GAGGATGCCT AGGAGATGTT GGGAACAGAA GAAATAAACT GAGTAAGG 10 GGGACTTAAA CTGCTGAATT C -3' (FRAG. NO:_) (SEQ. ID NO:2427) 5'-TTCCCAG ATGGGCAGAG GTGGCTGGGC TGGTGACCCT AAGTGTGTCT CCTGCCTTA TTCTCTCTAG TGGGTTATTC TTTCATGTGG TATCTTGCCT ACAGCATGCT GTGTTTGGAC ACAAACCCCT TTCCTTGGTT TCTCTGACCC AGCTGAGATG GACTGATTCC AAAAGAACTC ACCTATGTAC TGGGGTAGGG GAGGGAGGGT TTTTTGCAGT ATTTAACTAA GGTTCAAAGA GTGCTATATA GTGAGAAAGG CTTCTTT TTTTTTT-TT 15 TTTTGGCA GAGTGCTGCC TCCTAGAAAT TTCTCTTGGT AACTTCCTTC TCTGAAGCAC AGATAAAGAA AACAATTACA GTAGAAACAT TTATGAGGGA CACATTGGAG GCCGATGAAG CTITTCAAGT TCCAGCAGTG CAGGGATGTG GGCAGAACTG ACATTGGAAA ATACTAGAAT GATGGAAATT CAGTTGGAGA GGACTGCCCT TTTAATGTC TGGGGAGTCT GCTCAGGGAG AAATGACAAG TCTGGCGGGG ACAAGTATGG GATTTGGTAA GACTTGGATC AACTTGGGAT ACAGGGTGGG GGTCGGGAGT GGAATCAATG AATGATGCCA GAGCAGATCA 20 ACTAACAAGA GGACCCTGAT GAGCCCCAGG CAGAGGCGTC TCCCTTATGC CCCACTCTGA AGTGTTTGTT AGTAAACACC AGAACGCCAT TGTTGTTACT GCTGAATTTT ATTTTGGGCT GTACATATTT AGATGCTTAA GGTAAAAATG ATAAAGCCCT CAAGCCACTG TGTGGGTTTG GGTCCAAGTG TTCCTTCTTG CTGCCTCTCT AACACGCCTG GTTAAAATAA TCCCTTTGGA TGGTGCTGAG AAGCACCTGA ACCAAGTGGG TCCCCAAATA ACAATGGCGT GCAAGTGTCT GGTTCCCAGA AGTTGGTGAC TAGGTAAGCA GCTTCAGGGA GAGGGGGCTG 25 ATTCCCAGAC AGTCGCCTGT TCCTGCGGGG ATGGGGCTGA GGCTTGGGGA ATGTGGGCAG GAGGATATGC CATTTGATTC TGTTGCACAC GTTCTITCC CTrCTTTCTG TATGTCTGGT CATrCTGCTA TT7CTGTCGTT CCTCACATAG GTTGGACATT GGCCGGCTGC CAGCATAAGT GCCAGTGTGA TTTTGCTAGG TGTGAGCTGA GAAAGAGAGG TGGAGGCTAA GCAGGTGTGA TGCTTCTCAG AGGTGCTGAG TTTTTGCCCT TCTGAGCAGG GAATCTTTGC TTATCCCTTT GACCAAGGAT CTTTGCTGCA AAGGCTGGGT ATCGGCTGTG CTCAGCAAAG 30 CGTCAACTCG TGCAAGAACT TAGCAGGAAT AGTTCTGGCT AAGGTTAGGA GGCTGCCACC AAAGTCTCTT TTTTGTTCCT CTGCTTCTCC CGTTTGCCTC CTTATCATGA GATCTTTG CTAAGCTGGC AGAAAGATTG CATAGTCAGT GCTTCCAGCT CTGCTCCCAC CTGATCCTGC ACTGTCCTCT GGTCCCTGAA TGAATGAACT CTGATACCCA ATCTTGTCTC GAGCCTTCTC TATGCCACTC ATGGCTCCTC TrCTGCTCTT TCCATCTTTT TGCTGAGAGT TCTGAGCTCT GTACTTCCTC TTGGCCCATC TCACTTCCTG AAACACCCCT GAAGAGGGTT 35 GCTTATCTTG ATGGAACTCA AAAAGCCAAA AAGCTGCAGG CAGAGGCGTT GAGGACATCT GTTTGGGGAA CTAAGAGCAG CAGCACTTTC AGATTCAGTC CATATAGAGC TGTCCTACAG CATTCTGGAA ACTTGAGGAT GTGCGGTGCA TAAAGGGGCT GGAAGTGACC CACCTGTGAT GAGCCCTC TAAGGAGAAG GGTTTCCAAG AGATCACCCC ACCAGAAAAG GGTAGGAATG AGCAAGTTGG GAATTTTAGA CTGTCACTGC ACATGGACCT CTGGGAAGAC GTCTGGCGAG GCTAGGCCC ACTGGCCCTA CAGACGGATC TTGCTGGCTC ACCTGTCCCT 40 GTGGAGGTTC CCTGGGAAG GCAAGATGCC CAACAACAGC ACTGCTCTGT CATTGGCCAA TGTTACCTAC TCACCATGG AAATTTTCAT TGGACTCTGC GCCATAGTGG GCAACGTGCT GGTCATCTGC GTGGTCAAGC TGAACCCCAG CCTGCAGACC ACCACCTTCT ATTTCATTGT CTCTCTAGCC TGGCTGACA TTGCTGTrGG GGTGCTGGTC ATGCCTGG CCATTGT7GT CAGCCTGGGC TCACAATCC ACTTCTACAG CTGCCTTT ATGACTTGCC TACTGCTTAT CTTTACCCAC CCTCCATCA TGTCCTTGCT GGCCATCGCT GTGGACCGAT 45 ACTrGCGGGT CAAGCTTACC GTCAGGTAGC CTGCGGCGTG GGGTGGGCAG CAATTGAGGC AGCTGGGAAA TGAGGCTACA AGCCAGAGC-3' (FRAG. NO:_) (SEQ. ID NO:2426) 5'-GGGCAATTTG TTAGTTATCC GCCGCCACCA AGACGCGGCA CGGCGCCTGG ACCGGAGGGG CCCCGCGCGG GCGCGAACTT TGGGCTCGGG CGAGTGGGTG GTGCTCCGCC CAGCCCGAGA CGGGCGGGCG CGCGGGCCAA TGGGTGCCGC CTCTTGGCCG CGGGGGGCCC CGACCCGTGG GTCCCGGCCA CCAGCGCCCC AGCCCCGAGG 50 CTCAGAAGCG GCAGGCGGAG GCGCGGTCCG GGCGCTATGG CCATGCCCGG CGGGTCTCAC GCGGCTGCCC CTCGCCCGGC GCGCCTrCGG TAGGGGGCGC CCGGGGCCCA GCTGGCCCGG CCATGCTGCT GGAGACACAG GACGCGCTGT ACGTGGCGCT GGAGCTGGTC ATCGCCGCGC TTTCGGTGGC GGGCAACGTG CTGGTGTGCG CCGCGGTGGG CACGGCGAAC ACTCTGCAGA CGCCCACCAA CTACTTCCTG GTGTCCCTGG CTGCGGCCGA CGTGGCCGTG GGGCTCTTCG CCATCCCCTT TGCCATCACC ATCAGCCTGG GCTrCTGCAC TGACTTCTAC 55 GGCTGCCTCT TCCTCGCCTG CTTCGTGCTG GTGCTCACGC AGAGCTCCAT CTTCAGCCTT CTGGCCGTGG CAGTCGACAG ATACCTGGCC ATCTGTGTCC CGCTCAGGTA TAAAAGTTTG GTCACGGGGA CCCGAGCAAG AGGGGTCATT GCTGTCCTCT GGGTCCTTGC CTTTGGCATC GGATTGACTC CATTCCTGGG GTGGAACAGT AAAGACAGTG CCACCAACAA CTGCACAGAA CCCTGGGATG GAACCACGAA TGAAAGCTGC TGCCTTGTGA AGTGTCTCTT TGAGAATGTG GTCCCCATGA GCTACATGGT ATATTTCAAT TTCTTTGGGT GTGTTCTGCC 60 CCCACTGCTT ATAATGCTGG TGATCTACAT TAAGATCTTC CTGGTGGCCT GCAGGCAGCT TCAGCGCACT GAGCTGATGG ACCACTCGAG GACCACCCTC CAGCGGGAGA TCCATGCAGC CAAGTCACTG GCCATGATTG TGGGGATTTT TGCCCTGTGC TGGTTACCTG TGCATGCTGT TAACTGTGTC ACTCTTTTCC AGCCAGCTCA WO 00/62736 PCT/USOO/08020 130 GGGTAAAAAT AAGCCCAAGT GGGCAATGAA TATGGCCATT CTTCTGTCAC ATGCCAATTC AGTTGTCAAT CCCATTGTCT ATGCTTACCG GAACCGAGAC TTCCGCTACA CTTTTCACAA AATTATCTCC AGGTATCTTC TCTGCCAAGC AGATGTCAAG AGTGGGAATG GTCAGGCTGG GGTACAGCCT GCTCTCGGTG TGGGCCTATG ATCTAGGCTC TCGCCTCTTC CAGGAGAAGA TACAAATCCA CAAGAAACAA AGAGGACACG GCTGGTTTTC 5 ATTGTGAAAG ATAGCTACAC CTCACAAGGA AATGGACTGC CTCTCTTGAG CACTTCCCTG GAGCTACCAC GTATCTAGCT AATATGTATG TGTCAGTAGT AGGCTCCAAG GATTGACAAA TATATTTATG ATCTATTCAG CTGCTTTTAC TGTGTGGATT ATGCCAACAG CTTGAATGGA TTCTAACAGA CTCTTTTGTT TTTAAAAGTC TGCCTTGTTT ATGGTGGAAA ATTACTGAAA CTATTTACT GTGAAACAGT GTGAACTATT ATAATGCAAA TACTTTTTAA CTTAGAGGCA ATGGAAAAAT AAAAGTTGAC TGTACTAAAA ATG-3'(FRAG. NO:_)(SEQ.ID NO:2425) 10 5'-GBG CB TGC-3' (FRAG. NO:1676) (SEQ. ID NO:1691) 5'-TTG TTG GGC-3' (FRAG. NO:1677) (SEQ. ID NO:1692) 5'-TGC CTT CCC BGG G-3' (FRAG. NO:1678) (SEQ. ID NO:1693) 5'-GTT GTT GGG CAT CTT GCC-3' (FRAG. NO:1679) (SEQ ID NO:3) 5'-GTG GGC CTA GCT CTC GCC-3' (GRAG. NO:1680) (SEQ ID NO:5) 15 5'-ACA GAG CA TGC TGT TGT TGG GCA TCT TGC CTT CCC AGG G-3' (FRAG 982) (SEQ. ID NO: 992) 5'-BCB GBG CB TGC TGT TGT TGG GCB TCT TGC CTT CCC BGG G-3' (FRAG 983) (SEQ. ID NO: 993) 5'-CCC TTT TCT GGT GGG GTG-3' (FRAG 984) (SEQ. ID NO: 994) 5'-GTG CTG TTG TTG GGC-3' (FRAG 985) (SEQ. ID NO: 995) 5'-TT CTT CTG TTC CC-3' (FRAG 986) (SEQ. ID NO: 996) 20 5'-CCC TT TCT GGT GGG GTG-3' (FRAG 987) (SEQ. ID NO: 997) 5'-GTG CTG TTG TTG GGC-3' (FRAG 988) (SEQ. ID NO: 998) 5'-TTT CTT CTG TTC CC-3' (FRAG 989) (SEQ. ID NO: 999) Human IgE Receptor p Nucleic Acid and Antisense Oligonucleotide Fragments 5'-TTT CCC CTG GGT CTT CC CTC CTG CTC TTT TTT C ATT TGC TCT CCT ATT ACT TTC TGT GTC CAT TTT 25 TTC ATT AAC CGA GCT GT BTT TGC TCT CCT BTT BCT TTC TGT GTC CBT TT TTC BTT BBC CGB GCT GT 3' (FRAG. NO:1681) (SEQ. ID NO:1694) 5'-CCC CTG GG-3' (FRAG. NO:1682) (SEQ. ID NO:1695) 5'-GCTCTCCTBTT-3' (FRAG. NO:1683) (SEQ. ID NO:1696) 5'-CBTTBBCCGBGCTG-3' (FRAG. NO:1684) (SEQ. ID NO:1697) 30 5'-TTT CCC CTG GGT CTT CC-3' (FRAG 990) (SEQ. ID NO: 1000) 5'-CTC CTG CTC TTT TTT C-3' (FRAG 991) (SEQ. ID NO: 1001) ATTTGCTCTCCTATTACTTTCTGTGTCCATTTTTTCATTAACCGAGCTGT (FRAG 992) (SEQ. ID NO: 1002) BTT'rGCTCTCCTBTTBCTTTCTGTGTCCBTTTTTCBTTBBCCGBGCTGT (FRAG 993) (SEQ. ID NO: 1003) Human Fc-s Receptor CD23 Antigen (IgE Receptor) 35 Nucleic Acid and Antisense Oligonucleotide Fragments 5'-GCC TGT GTC TGT CCT CCT GCT TCG TTC CTC TCG TTC CTG CTT GGT GCC CTT GCC G GTC CTG CTC CTC CGG GCT GTG G GTC GTG GCC CTG GCT CCG GCT GGT GGG CTC CCC TGG CCT TCG CTG GCT GGC GGC GTG C GGG TCT TGC TCT GGG CCT GGC TGT GGC CGT GGT TGG GGG TCT TC GCT GCC TCC GTT TGG GTG GC TCT CTG AAT ATT GAC CTr CCT CCA TGG CGG TCC TGC TTG GAT TCT CCC GA TCT CTG 40 BBT BTT GBC CTT CCT CCB TGG CGG TCC TGC TTG GBT TCT CCC GB-3'(FRAG 1685)(SEQ.ID NO:1698) 5'-GT CCT CCT-3 (FRAG 1686) (SEQ. ID NO: 1699) 5'-TGT GTC TGT CCT CC-3' (FRAG 1687) (SEQ. ID NO: 1700) 5'-GTG GCC CTG GC-3' (FRAG 1688) (SEQ. ID NO: 1701) 5'-CGT GGT TGG GG-3' (FRAG 1689) (SEQ. ID NO: 1702) 45 5'-TCT CTG BBT BTT GBC C-3' (FRAG1690) (SEQ. ID NO:1703) 5'-GCC TGT GTC TGT CCT CCT-3' (FRAG 994) (SEQ. ID NO: 1004) 5'-GCT TCG TTC CTC TCG TTC-3' (FRAG 995) (SEQ. ID NO:1005) 5'-CTG CTT GGT GCC CTT GCC G-3' (FRAG 996) (SEQ. ID NO: 1006) 5'-GTC CTG CTC CTC CGG GCT GTG G-3' (FRAG 997) (SEQ. ID NO: 1007) 50 5'-GTC GTG GCC CTG GCT CCG GCT GGT GGG CTC CCC TGG-3' (FRAG 998) (SEQ. ID NO: 1008) 5'-CCT TCG CTG GCT GGC GGC GTG C-3' (FRAG 999) (SEQ. ID NO: 1009) 5'-GGG TCT TGC TCT GGG CCT GGC TGT-3' (FRAG 1000) (SEQ. ID NO: 1010) 5'-GGC CGT GGT TGG GGG TCT TC-3' (FRAG 1001) (SEQ. ID NO: 1011) 5'-GCT GCC TCC GTT TGG GTG GC (FRAG 1002) (SEQ. ID NO: 1012) 55 5'-TCT CTG AAT ATT GAC CTT CCT CCA TGG CGG TCC TGC TTG GAT TCT CCC GA (FRAG 1003) (SEQ.ID NO:1013) 5'-TCT CTG BBT BTT GBC CTT CCT CCB TGG CGG TCC TGC TTG GBT TCT CCC GB FRAGG 1004) (SEQ.ID NO:1014) Human IgE Receptor a Subunit Nucleic Acid and Antisense Oligonucleotide Fragments 5'- GCC TTT CCT GGT TCT CTT GTT GTT TTT GGG GTT TGG CTT ACA GTA GAG TAG GGG ATT CCA TGG CAG GAG CCA TCT TCT TCA TGG ACT CC TTC AAG GAG ACC TTA GGT TTC TGA GGG ACT GCT AAC ACG 60 CCA TCT GGA GC BCB GTB GBG TBG GGG BTT CCB TGG CBG GBG CCB TCT TCT TCB TGG BCT CC TTC BBG GBG BCC TTB GGT TTC TGB GGG BCT GCT BBC BCG CCB TCT GGB GC GTT GTT TTT GGG GTT TGG CTT GCC TTT CCT GGT TCT CTT BCB GTB GBG TBG GGG BTT CCB TGG CBG GBG CCB TCT TCT TCB TGG BCT CC TTC BBG GBG BCC TTB GGT TTC TGB GGG BCT GCT BBC BCG CCB TCT GGB GC-3' (FRAG. NO: 1691) (SEQ. ID NO:1704) WO 00/62736 PCT/USOO/08020 131 5'- TGG BCT CC -3' (FRAG. NO: 1692) (SEQ. ID NO:1705) 5'-CCB TCT GGB-3' (FRAG. NO: 1693) (SEQ. ID NO:1706) 5'-CT GCT BBC BCG-3' (FRAG. NO: 1694) (SEQ. ID NO:1707) 5'-GTT TTT GGG GT TG-3' (FRAG. NO: 1695) (SEQ. ID NO:1708) 5 5'-GCC TTT CCT GGT TCT CTT GTT GTT TTT GGG GTT TGG CTT-3' (FRAG. NO:1005) (SEQ. ID NO:1015) 5'-ACAGTAGAGTAGGGGATTCCATGGCAGGAGCCATCTTCTTCATGGACTCC-3'(FRAG.NO:1006)(SEQ.ID NO:1016) 5'-TTC AAG GAG ACC TTA GGT TTC TGA GGG ACT GCT AAC ACG CCA TCT GGA GC-3' (FRAG. NO:1007) (SEQ. ID NO:1017) 5'-BCB GTB GBG TBG GGG BTT CCB TGG CBG GBG CCB TCT TCT TCB TGG BCT CC TTC BBG GBG BCC TTB 10 GGT TTC TGB GGG-3' (FRAG. NO:1008) (SEQ. ID NO:1018) 5'-BCT GCT BBC BCG CCB TCT GGB GC-3' (FRAG. NO:1009) (SEQ. ID NO:1019) 5'-GTT GTT TTT GGG GTT TGG CTT-3' (FRAG. NO:1010) (SEQ. ID NO:1020) 5'-GCC TTT CCT GGT TCT CTT-3' (FRAG. NO:1011) (SEQ. ID NO:1021) 5'-BCBGTBGBGTBGGGGBTTCCBTGGCBGGBGCCBTCTTCTTCBTGGBCTCC-3'(FRAG.NO:1012) (SEQ.ID NO:1022) 15 5'-TTC BBG GBG BCC TTB GGT TTC TGB GGG BCT GCT BBC BCG CCB TCT GGB GC-3' (FRAG.NO:1013) (SEQ.ID NO:1023) Human IgE Receptor (Fc Epsilon R) Nucleic Acid and Antisense Oligonucleotide Fragments 5'-GCC TGT GTC TGT CCT CCT GCT TCG TTC CTC TCG TTC CTG CTT GGT GCC CTT GCC G GTC CTG CTC CTC CGG GCT GTG G GTC CTC GCC CTG GCT CCG GCT GGT GGG CTC CCC TGG CCT TCG CTG GCT GGC 20 GGC GTG C CCC BGB BCG BGB CCC GGB CCG BCB GGC CGT GGT TGG GGG TCT TC GCT GCC TCC GTT TGG GTG GC GAT CTC TGA ATA TTGA CCT TCC ATG GCG GTC CTG CTT GGA GBT CTC TGB BTB TTGB CCT TCC BTG GCG GTC CTG CTT GGB-3' (FRAG: 1696) (SEQ. ID NO:1709) 5'-TCG TTC CTC TCG-3' (FRAG: 1697) (SEQ. ID NO:3001) 5'-BGB BCG BGB C-3' (FRAG: 1698) (SEQ. ID NO:1711) 25 5'-TGB BTB TTGB-3' (FRAG: 1699) (SEQ. ID NO:1712) 5'-GCC TGT GTC TGT CCT CCT-3' (FRAG. NO:1014) (SEQ. ID NO:1024) 5'-GCT TCG TTC CTC TCG TTC-3' (FRAG. NO:1015)(SEQ. ID NO:1025) 5'-CTG CTT GGT GCC CTT GCC G-3' (FRAG. NO:1016)(SEQ. ID NO:1026) 5'-GTC CTG CTC CTC CGG GCT GTG G-3' (FRAG. NO:1017)(SEQ. ID NO:1027) 30 5'-GTC CTC GCC CTG GCT CCG GCT GGT GGG CTC CCC TGG-3' (FRAG. NO:1018) (SEQ. ID NO:1028) 5'-CCT TCG CTG GCT GGC GGC GTG C-3' (FRAG. NO:1019) (SEQ. ID NO:1029) 5'-CCC BGB BCG BGB CCC GGB CCG BCB-3' (FRAG. NO:1020) (SEQ. ID NO:1030) 5'-GGC CGT GGT TGG GGG TCT TC-3' (FRAG. NO:1021) (SEQ. ID NO:1031) 5'-GCT GCC TCC GTT TGG GTG GC-3' (FRAG. NO:1022) (SEQ. ID NO:1032) 35 5'-GBT CTC TGB BTB TTGB CCT TCC BTG GCG GTC CTG CTT GGB-3' (FRAG. NO:1023) (SEQ. ID NO:1033) Human High Affinity IgE Receptor Oligonucleotide Fragments 5'-AACAAGAAAA GCGTTGGTAG CTCTGGTGAA TCCCAAAAGA ATGTGGCAGT TGCTAGCCAT GCTCCTGAAT ATGTATAAAC AGTACATCAT ATGACTAAGA GTTTGACTTA GGGGTTAGAT TTTATGTGTT TGAACCCCAA ATTAGTTATT TAATAGTTGG CACCCCAAAA CAAGTTACTT AACCTCACTA AGGTTCAGTT TTCCTGTTTA 40 TAAAATGTAG ATAGTGATAG TATGTACTTT ATAGGATTAT TGTGAAAAAT AAATGAAATA TCAGATTTAT TTAGGATAAC ACCTGGCATA TGTTTGGTAT TCAGAATTAG TTGCTGCTGT TTTATTCTGC TCTCCCTTGC ATCCCACTT TCTAAGTTGT AAACTAAATA GTTGTACACA GATTGACAGA TTAAGAAAGG CTTGTGATrG TGCTAGACCT ATGCCTATGC CTCTGTCTCA CCAGATTCCA GGTGTATATG TGGAGGTGGG ATAGGGAGTG GAGTAAGTGG GTAAATATTA AATTGCCCAG TTGGGCACCA TCCTGAATAT TATCTCTAAA GAAAGAAGCA 45 AAACCAGGCA CAGCTGATGG GTTAACCAGA TATGATACAG AAAACATTTC CTTCTGCTTT TTGGTTITAA GCCTATATT'T GAAGCCTTAG ATCTCTCCAG CACAGTAAGC ACCAGGAGTC CATGAAGAAG ATG GATCTTCATG TGGAATGACT GGTTTCATTC AATAGACTTA ATTCAGCAGT CTGTGGGGAA GAGCAAGGTA TGATAGAATG GTTCCTCAAG TGCTTCAGAT GTGAAGTGGG TTTAAATATA CTGTCCCTGT CTTCTTCAGA GTTTTGGTAA AGATAAAATA GGACACTCAT TTAAAAGCAA TCTTTGCAAA TGACAAGCCA CTATAGACAT 50 TAATAGAGTT TTCATTTCCA GTATTATCAT TAATATCAGA TCCTGGAAGA AGGTTGAGCC TTGACCTAGA GCAAAAAAAC AGAAGAATTA GTAAAGGAAT CCTGGAGAAA GCCCCTGCTG TGTATTTAAA GGAGAAAGGG AGATCATGTT GGGAAATTAT AATATTAAAA GTAAACAAAA GCTAGGAAGT AAAATAAAAT AAATTATATG GCCTAGATCC CCATAAGTAA TGGTTTAACT TCTGCCTTCC TGTGTTCTGA GCCAGATTAG GGCACAGTAG AGAAAGAGGA GTCTCTGAAA ATGTTTCCAA TTTCGCTGGT CAGACAGCGG ATCATCAGTG AATCAGATGA 55 AAATTTGTGG ATTTATGCAC TAACTGATCA GCAGGAAATT AAACAAGAAA AGCGTTGGTA GCTCTGGTGA ATCCCAAAAG AATTTGGCAG TTGCTAGCCA TGCTCCTGAA TATGTATAAA CAGTACATCA TATGACTAAG AGTTTGACTT AGGGGTTAGA TTTTATGTGT TTGAACCCCA AATTAGTTAT TTAATAGTTG GCACCCCAAA ACAAGTTACT TAACCTCACT AAGATTCAGT TTTCCTGTTT ATAAAATGTA GATAGTGATA GTATGTACTT TATAGGATA TTGTGAAAAA TAAATGAAAT ATCAGATTTA TTTAGGATAA CACCTGGCAT ATGTTTGGTA 60 TTCAGTAATT AGTTGCTGCT GTTTTATTCT GCTCTCCCTT GCATCCCACT TTTCTAAGTT GTAAACTAAA TAGTTGTACA CAGATTGACA GATTAAGAAA GGCTTGTGAT TGTGCTAGAC CTATGCCTCT CTCTCACCAG ATTCCAGGTG TATATGTGGA GGTGGGATAG GGAGTGGAGT AAGTGGGTAA ATATTAAATT GCCCAGTTGG GCACCATCCT GAATATTATC TCTAAAGAAA GAAGCAAAAC CAGGCACAGC TGATGGGTTA ACCAGATATG ATACAGAAAA CATTTCCTTC TGCTTTTTGG TTTAAGCCT ATATTTGAAG CCTTAGATCT CTCCAGCACA 65 GTAAGCACCA GGAGTCCATG AAGAAGATGG CTCCTGCCAT GGAATCCCCT ACTCTACTGT GTGTAGCCTT WO 00/62736 PCT/USOO/08020 132 ACTGTrCTrC GGTAAGTAGA GATICAATTA CCCCTCCCAG GGAGGCCCAA ATGAA'ITTGG GGAGCAGCTG GGGTAGGAAC CTIACTGTG GGTGGTGACT PTFCTAGGA CATGTGCAAA CTATTGGGCA TTTCCCAGGG ACTCTGTAGT GGAGCCAAGC TAGAAAGCAG AGGCAAGTGG GCTGAGCAAC ACCTAAGGAG GAAGCCAGAC TGAAAGCTrG GTTCCTTGCA =IGCTCTGG CATCTTCCAG AGTGCAAATT TCCTACCAAG GTAATGAGGG 5 TAGAGGAGAG AAAGAAGCTC T'TTCTTCCCC TGATTCTCAT TCCTGAAAAG ACGG'rTGGTC CTTAAAATTC CATGGATGTA GATCTTATCC CCACACCCAG ATTCTAGTCC TCTGGAGATA AAGAAGACTG CTGGACACTA ATGTATCCTC TCTGGACTIT TGCAGCTCCA GATGGCGTGT TAGCAGGTGA GTCCTCTGTT CrrGTITCCCT TGGTGTATCA ACATGTCTGG GCATTGCTTT CCTCTCACTA 'TTTTC17CGT CCCATCACTT CTGCTTTCTA ATGAGCATGA ATCTG'FrCCT TGGCCAGACT ACT'FCCCTC TCCACCTTGC CMGTCI=C rrrrrvccc 10 TGATTCAI1?G CAYFCTCTCA AGTCATTCTC TCCTCTGTIT TAGTCAATAA CCATGTCTGT TGCACATATA CATGTCTCAT TCTCTCTCCT AGACACTTTG GCATGATCTC GCTCAATAAT TACAYFATTA TI7ATrAFIGC CATITTATAA TTGAGGATGC TGAAACTCAG TGA=IICTG GTGGTI'ACAT GGCTAAGGAA CTGGATTTCA ACGTAAGTTC CTTGGATCTA AGTCCAGTT1C TCTTCTGACT ATATCACCCT TFTGTTATCA CCATGTATCT ACTrCM]GG TCTCTG FTCA AA'Tr7GCACT ACATCCCCTT G'ITCCAGGAA GCCATTCAAG ACTGACTrTC 15 TTAGTGCCTC TCACTACYI17 CTGGAACTGA CATATGTIT TCACTCTGTA TATACTT1ACA ATTAAATAGT CATAAATATI' CAGAGC FTGG AGAAACCTFA TA1TTTCATCC AGTCCAGTAA ATIATCCAT CCATAATTCA CTCATTCATT CACATAATAA ATATTTAATG TAACAATGGT TGAACATGGC AGACAGTGTT TCTACCTCAA AAGAGAYI'GC AGTCCTCATT TACAGATACT GAATTGAAAT TAACAGAAGT AGAGTGAGTC AGCTCAAATC ACATAGTGAA TTGG'ITTCT? TGT=~AAA TCTCCTGCAT ATGTGTCCTG TCTrCTCCC TGTGT7GGGC 20 GTTCCCTGGG GCACCAATAC TAATTTCTCC TTCCCCTAGA AATCAAAACA GGGTCTTATC ACCAACAGAA TAAGGACAGG TTGACCACTG A'I1GTCAGAA TATTGC'rrCG MTGTAC'rrr TAAGCCTAGA CAGTTTTCAA TGAC'TT TCTCTCTACA TGTCT11CA TA'TTMATC TTCTTGAAGT CCCTCAGAAA CCTAAGGTCT CCTTGAACCC TCCATGGAAT AGAATATI1A AAGGAGAGAA TGTGACTCTT ACATGTAATG GGAACAAM1 CTrTGAAGTC AGTTCCACCA AATGGTrFCCA CAATGGCAGC CT=CAGAAG AGACAAATTC AAG'TrGAAT 25 ATTGTGAATG CCAAATTGA AGACAGTGGA GAATACAAAT GTCAGCACCA ACAAGTI'AAT GAGAGTGAAC CTGTGTACCT GGAAGTCTrC AGTGGTAAGT TCCAGGGATA TGGAAATACA GATCTCTCAT GTGAGGGATG GCTCATCTGA AGATGGGAAA AAACAGGTTA TTCCAAGGGT TAGGACACCA GAGTGGGATT CAAGGCCTCT CATITTTAAG ACCCCTGCAT TGGCTGGGCA CAGTGGCTCA CGCCTGTAAT CCCAGCACTT TGGGAGGCTG AGGCAGGTGG ATCACGAGGT CAGGAGATCG AGACCATCCG GCTAACATGG TGAAACCCCA TCTCTGCTAA 30 AAAATATATA TATATAAAAT TAGCCGGGCG TAGTGGTGGG CACCTGTAGT CCCAGGTACT CGGGAGGCTG AGGCAGGAGA ATGGTGTGAA CCCAGGAGGT GGAGGTTGCA GTGAGCTGAG ATCACGCCAC TGCCCTCCAG CCTGGGCTAC AGAGCAAGAC TCCGTCTCAA AAAATAAATA AATAAATAAA AAAGACCCCT GCATCTCMr TCTTCTACCC CCYI1CCCTfl7 TGATTACTTG TATGCCTTCT TTCAATATJ7C TAGTCATCTC TCAATATTAT TCCTCCACCC TATITCCTC TATCTITCT GCCTAGATrC AGGTATATAT TATGTGGTCA AACAGCATGA 35 CATATATGTG AACATICAA AGAGCTGTGT ATCTGGAATA GGATCAAAAG GTP1TGACTTA AAGTITGCT CTGCATAATC CATATGGCAG GACCTGAATA TTAGGTTGTA CTCT7CGTA TGAAACATAT CTGGGTACAT TTCCT'TATGT CCTCTG fGT TAC11'AAGAA CACATAITTC ATGCT7G IT CA'TFI=ATC ACTCCTACTG CCAACAAATA GCATAGCATG CTTAGGCACA TGTGGCT-FAA TTAGCAAATG 'ITGAATAAAC AAATTAATGA 'VTMGAATAG TGACCAATAG GTCTC'T17A TACTCTATAT 'TTTCTCTrG AGTGAAAAAA AATGTTTCAA 40 CCTCCATATG TAAATTCCAA ACACAAACTA AAGCAATGTA GAATAGCTTC TrATTCCCT GGAGTAGGTT CTAGAGAAGT CCTAAAGGAT TGGTCCTAAA TTAATTATGC TrATTATGCT AGCGATATr CC'TrCAAAA TrCTCCTrA ATGAATGCTT TTTAATTT ACAAAAGCAT TAACCATAGA ATGTGA'TrCT TGTCTITCAC TGACTCATTA GTGACAAATA 'TrGTTGAGT ACCTACCAAC TCCTAAGTAT TGCTACCAAC TCCTAAATAC TGTGTTGGGC ATTCAGAATA GAATGTAGAA CTAGACAGGG TCCCTGACTr CTrGGAGCAC AGAGCAGTAT 45 GGGAAGAGGA CATTAAATAA AGAATI'ACAT AAGTAATI'AA TTAAATrAT ACATGITIG AAGAAGTIT1 TITIGACAA CTATAATTAA CACTAGAACT GGGAAGTITC TATAAGGTAA GAGAGGACAA AATAGACACT CTCCTAAGCT AAAATTCCCA AGAAAGACTG TFrATICC CCTAACTAAC TAGAACTAGC AACAGAAGAT CTGAAAGGAA T~rCTGGCTI17 CAAGTGTT1CC ATGTATGGAC TCATCAGGGA GGTCCGAGAG GCTTTGTGGC CCCAGACTGA CTTTTCAGGA GGGGAAAGGA T7FIATCAATA CACAAGACAG GCTCTAAGCA TJATTTTGTG 50 ccc'TIAAAA ATCCAC'TrA TGAGCCAAAA AGTGAGTrAA TGATAAT-rCA TAGTrTCTGA CACATGCTCT ATGCGTGGCT CTC=FTCTC TATTCATTCT CTCTCTC.TTC AThr7ATTG~r AAATAAATAA TGTAATGAAT GFTCT'TCAGA CTGGCTGCTC C'ITCAGGCCT CTGCTGAGGT GGTGATGGAG GGCCAGCCCC TCTrTCCTCAG GTGCCATGGT TGGAGGAACT GGGATGTGTA CAAGGTGATC TATIATAAGG ATGGTGAAGC TCTCAAGTAC TGGTATGAGA ACCACAACAT CTCCATTACA AATGCCACAG TTGAAGACAG TGGAACCTAC TACTGTACGG 55 GCAAAGTGTG GCAGCTGGAC TATGAGTCTG AGCCCCTCAA CATTACTGTA ATAAAAGGTG AGTTGGTAAA GGAAAGGAAA AGCATCCATA GCAGGGGAAG GAAGAGAGAA CTTCTGAGCC TGAGCAG TrG CAGC317GTAG AAGGGGGGCA CCTGTGATAC ACTGGAAAGC CTACCAGACT TGCAATGAGG AGACCTGGGT GATAGTATAT ATCTCAATCT CTGMrCAAA GCCT7GACTT GTTAAATGGT GATAGTAATA CCTGCTTGCA CTATGAAATT TTTATGAAGA TTAATGTGGT AATATGTG AAATGACT GTAAACTGTI' AAGCACTACC CAAGCATAAC 60 AGATTGTGAT TACTAYTMG ATCTCAAAGT CATCTGT-rGC TCCTGGGGGA ACACTI1ATAT 'rrATCAAA'rr GAAAAAAAGT 'FrCAAAGTTG AATGAAGAAA GGATATAAAG AGCTrGAGGA GCCCATTCCA GCYI'AGGAGG GCTGGGAAAG GAAACCAGCA AGTCAGTAAG CTGTGTGCCT GTGTATTGAG GGAGGAGGGA ATGGAC FTGA TATGGAGAGG GTAGGGAGGT GGACTGCCTC TATGGCCTGT AAGAAAAACT GCTCTCTCCA AACTCTTTAT AAGAGAGGGA GCCTGTGAAG TATTCAC'rrT TGAAGGAGAA AGTTAGAC'IT ITCCTTCACA CACTTTGTAC 65 ATAATAATGT TTAAAAAAGC ATGAGGTCAA AATACATAAT TAAGTCCTAG CAG ITCTCTG TTAACTAAKI1 TGAGACTGAA GTGCTATGTA CT7GTCTCTA GGCTTCCAGT ATC ITCATCT GTAAAACAGA ATATTGGTC WO 00/62736 PCT/USOO/08020 133 TAGA FrCCAT TAGAATCATT TGATAACTTA AAAAATATAT TGATGCTCAT GTCTCATrTC TrGAGArrCT GATTrAATI7G GTTrGGGGTG CAGCCTGGGT ATACGTAYIT ITFCATAGGTC 1TTCACATAA TGGTAATGGG TAGCCAATAT TGAGAATCAC TTGTCTAGGT GATCTI-rAAA TGA'1CTGG ATGTAATA117 CTGAGGCTCT ATAATTGAG ACTAATCACA AAAATCGGTA CAG'TTATAA ACAGACTAAC AGAACCACAA AATAATAGAA 5 TTGGAAGGCA ATTFAACTAG TGCAA'TrCT TCATTrGCC TAACAGGCAT GTAAGAAATG ATGA'ITGATr GAGTAATAGG CATTGATGAC CCCTGTCCTC AC'ITTGTCCC CM~CCACCC CTTAATTATA TGTGAATTCT GGTCTTGTCA TTCGAATAA GGGGMEATC TTTCCTATTG TCTTCCCCTC TGGGCACGGC ACACTGGCTA CTGGAGTTAA GAGGAAATGC TI7AGGACTCC CTGTGGCTCC AGGGAGCACC AACAGAGCAA CTCAACCTAG TGTTAATCTG AGTGTTCT CTGTGCTTCT GGATGCCACA TCACGCTAAA AATGAAGGAC AAAGCTTGGT 10 CTTTCTCTTA GGGAGGATGA AACTCTGAAC CTCAT1TC AG11TCCCAAG ATGAA'FrATG TTTCTCATTG CATCTGTGTT CCACTACAGC TCCGCGTGAG AAGTACTGGC TACAA'TTT TATCCCA117G TTGGTGGTGA TCTGITI7GC TGTGGACACA G6ATTATTTA TCTCAACTCA GCAGCAGGTC ACATfCTCT TGAAGATTAA GAGAACCAGG AAAGGCTTCA GACTTCTGAA CCCACATCCT AAGCCAAACC CCAAAAACAA CTGATATAAT TACTCAAGAA ATATTGCAA CATTAGT1T TPTCCAGCAT CAGCAAT7GC TACTCAA FIG TCAAACACAG 15 CTTGCAATAT ACATAGAAAC GTCTGTGCTC AAGGATITAT AGAAATGCTT CA TAAACTG AGTGAAACTG GTTAAGTGGC ATGTAATAGT AAGTGCTCAA 'PTAACATTGG TTGAATAAAT GAGAGAATGA ATAGAFTCAT TTATTAGCAT TTGTAAAAGA GATG'ITCAAT TTCAATAAAA TAAATATAAA ACCATGTAAC AGAATGCrTC TGAGTATTCA AGGCTI'GCTA GTTGTI1'GT TTGT1TCTA CTAAAGGCAA GGACCATGAA GTTCTAGA11' GGAAATGTCC TCTCTTGACT ATTGCAAGTG CGATCTAGGA ATGAAAAGAC ATAGGAGGAT GCCAGTGAGG 20 TGGATCNITT TTATGCTrCT TCTTCAGCTr ACTAAATATG AAC=~CAGT TCT7GGCAGA ATCAGGGACA GTCTCAAGAC ATAGGACTCT CAGGATGAAG TAGAGTCCAG GATTCCTCTG TGATrGT1T GCCCCTCCCA AATTTATATC TTGAACTTFAT GTCT-rGTATC TrTATACAGC ACCTGAACCA AGCATIT[GG AGAAAYJ'CCA GCTAATAATA ATAACCAAAA CCTTCGGCTC TGAAAACAGT CCAGGACTGA ATAAGATCTr GGGCAAAAGA ACTAGACAGT TTTGGTAT MICCC1TrC ATITATGTC TTCATCATAG TCATTGGAGG CTCATTCTTC 25 TITGTCATGGA GTAAATGGGA TTAAAGTTC TACTAAGAGT CTCCAGCATC CTCCACCTGT CTACCACCGA GCATGGGCCT ATATTTGAAG CC'ITAGATCT CTCCAGCACA GTAAGCACCA GGAGTCCATG AAGAAGATGG CTCCTGCCAT GGAATCCCCT ACTCTACTGT GTGTAGCCTT ACTGT-FC11C GCTCCAGATG GCGTGTTAGC AGTCCCTCAG AAACCTAAGG TCTC=TGAA CCCTCCATGG AATAGAATAT TrAAAGGAGA GAATGTGACT CTTACATGTA ATGGGAACAA TC TTGAA GTCAGTTCCA CCAAATGGTT CCACAATGGC AGCCTTrCAG 30 AAGAGACAAA TTCAAG'I=G AATATTGTGA ATGCCAAATT TGAAGACAGT GGAGAATACA AATGTCAGCA CCAACAAGTT1 AATGAGAGTG AACCTGTGTA CCTGGAAGTC TTrCAGTGACT GGCTGCTCCT TCAGGCCTCT GCTGAGGTGG TGATGGAGGG CCAGCCCCTC TTCCTCAGGT GCCATGG'I1G GAGGAACTGG GATGTGTACA AGGTGATCTA TTATAAGGAT GGTGAAGCTC TCAAGTACTG GTATGAGAAC CACAACATCT CCATTACAAA TGCCACAGTT GAAGACAGTG GAACCTACTA CTGTACGGGC AAAGTGTGGC AGCTGGACTA TGAGTCTGAG 35 CCCCTCAACA TI'ACTGTAAT AAAAGCTCCG CGTGAGAAGT ACTGGCTACA A'I-rTTATC CCATTGTTGG TGGTGATTCT GTITGCTGTG GACACAGGAT TATATCTC AACTCAGCAG CAGGTCACAT TrCTCTTGAA GATTAAGAGA ACCAGGAAAG GCTTCAGACT TCTGAACCCA CATCCTAAGC CAAACCCCAA AAACAACTGA TATAA'ITACT CAAGAAATAT T-rGCAACATT AGTTITC CAGCATCAGC AATFTGCTACT CAATTGTCAA ACACAG = G CAATATACAT AGAAACGTCT GTGCTCAAGG A T7ATAGAA ATGCTTCATT AAACTGAGTG 40 AAACTGG FTA AGTGGCATGT AATAGTAAGT GCTCAATTAA CATTGGTTGA ATAAATGAGA GAATGAATAG ArrTCATTrAT TAGCATPGT AAAAGAGATG 1TCAA IMCA ATAAAATAAA TATAAAACCA TGTAACAGAA TGC FrCTGAG TAAAAAAAAA AAAAAAAAAA AAAAAAAA TCTCAATATA ATAATATTCT TTATTCCTGG ACAGCTCGGT TAATGAAAAA ATGGACACAG AAAGTAATAG GAGAGCAAAT CTTGCTCTCC CACAGGAGCC YI7CCAGTGTG CCTGCA ITG AAGTCTTGGA AATATCTCCC CAGGAAGTAT CTTCAGGCAG ACTATTGAAG 45 TCGGCCTCAT CCCCACCACT GCATACATGG CTGACAGTTr TGAAAAAAGA GCAGGAG11C CTGGGGGTAA CACAAAT'CT GACTGCTATG ATATGCC'IT1 G=IIGGAAC AGTTGTCTGC TCTGTACTTG ATATCACA CATTGAGGGA GACAYTT CATCATTTAA AGCAGGTTAT CCATTCTGGG GAGCCATA'I7 TrrrTCTATr TCTGGAATGT TGTCAATI1AT ATCTGAAAGG AGAAATGCAA CATATCTGGT GAGAGGAAGC CTGGGAGCAA ACACTGCCAG CAGCATAGCT GGGGGAACGG GAA'ITACCAT CCTGATCATC AACCTGAAGA AGAGC'LTGGC 50 CTATATCCAC ATCCACAGTT GCCAGAAA TT GAGACC AAGTGCT1TA TGGCTTCCTI' TTCCACTGAA ATTGTAGTGA TGATGCTGYI' TCTCACCATT1 CTGGGACTTG GTAGTGCTGT GTCACTCACA ATCTGTGGAG CTGGGGAAGA ACTCAAAGGA AACAAGGTf C CAGAGGATCG TG TrATGAA GAATTAAACA TATATTCAGC TACTTACAGT GAGTTGGAAG ACCCAGGGGA AATGTCTCCT CCCATI7GAIT TATAAGAATC ACGTGTCCAG AACACTCTGA TTCACAGCCA AGGATCCAGA AGGCCAAGGT CITGTTAAGG GGCTACTGGA AAAATITCTA 55 TTCTCTCCAC AGCCTGCTGG TYI7 AAGCT'TCA AAGGTGCAAT TGGATAAC'IT CTGCCATGAG AAATGGCTGA ATTGGGACAC AAGTGGGGAC AAYI'CCAGAA GAAGGGCACA TCTC'ITCTT TrCTGCAGTr CTTCTCACC TTCTCAACTC CTACTAAAAT GTCTCATI' CAGGTTCTGT AAATCCTGCT AGTCTCAGGC AAAATTrATGC TCCAGGAGTC TCAAAT1TC TTAMCATA TTAGTCTA TTTAGTAGAC TTCTCAAYF TTCTATTFCAT CACAAGTAAA AGCCTGTTGA TCTFAATCAG CCAAGAAACT TATCTGTCTG GCAAATGACT 60 TATGTATAAA GAGAATCATC AATGTCATGA GGTAACCCAT TTCAACTGCC TATTCAGAGC ATGCAGTAAG AGGAAATCCA CCAAGTCTCA ATATAATAAT ATTCITTF CCTGGACAGC TCGGTfrAATG AAAAAATGGA CACAGAAAGT AATAGGAGAG CAAATC'I1GC TCTCCCACAG GAGCCTTrCCA GGTAGGTACA AGGTATTATT YT' CTACC GTCAGTCACT TGTGGCAGGG GAAGTCATAG TCACGGTGCT TAGGAGATGA AACTATTG AThTAGGCAT GGATCCATCT AGTTT1AATT1A ATATATTGGG TATGAGGAAG CTACTTGCTG TAC'TCCAT 65 GTGGTrCTCT CTCCCTGGAG AGGAACATIT TTACTCAGCT TGCAAACTGG AAATAGATT TCTCACATTA GAAGCTCATT ITFCTGGGTAT GAGACAGGAG AG'FrCATACT GTGTATGTAG ATCTCTGGCT TCTGGGTCTG WO 00/62736 PCT/US00/08020 134 ACATGTGCTG AGGGACACAT ATCCTTCACA CATGCTTA TAAATACTI'G ATAAAGTAAC CTGCTrrCTrrG ATTrGGTCTJ1' ATAATCCATA AGCTGTGGGA TGCTTCTCTG AAGATGAAAA TAGTAATAGA GTCCCATCTA GCTATrCAAA GCCATTCCTT CA'ITGTATI'C TGTGCACATG AAGTrGGGGT TTGTTACTGA CAAAATATAT TCAGATACAT TrCTATGTrA AAAGGAT1'GT GAGATGCATA GGTAAATGTG Tf~TT CA GTTITACTTG 5 TCAACATAGA TGAATGAGAA AGAACTTGAA AGTAACACTG GATTAAGAAT AGGAAAATTT GGCATGGATT TTGCTCCA'r TTGTCCCATC TAATCACTTG GATAGTGTTC AGGTGYTCTT GGTCAGTTAC TTGGATGCTC TGAGC'ITTAG ITTC1-TGGTG ATTACAATGA AGA'TI'GAAT TACAGGATGG CTTTGAAAAA ATAAACAAAA CTCCCC-TrC TGTCTGTCGA GAATGTTGCA CAGGGAGTTA CAGAATGITrC TCATGACTGA ATT1GCTTI17A AATTTCACAG TGTGCCTGCA TTGAAGTCT TGGAAATATC TCCCCAGGAA GTATCTTCAG GCAGACTATI' 10 GAAGTCGGCC TCATCCCCAC CACTGCATAC ATGGCTGACA GTrTGAAAA AAGAGCAGGA GTTCCTGGGG GTGAGTGAGC CTCCTCCAAC 'ITTGACTAGA GTAAGGGTTG GGTCTAGAAA AGAATATTGA G'ITGCATCAA CTGTTCCC AC=GGATTC ATGAGAGGTG TTAGGTCCTr TAAAAAACAT GGTAGATAAA GAGTTGACAC TAACTGGGTC C'TTrGGGAA GAGCCAGAAG CATTTCCTCA TAAAGAC'IrT AAATTGCTAG GACGAGAATG GCCAACAGGA GTGAAGGATT CATAAC'IMA TC'ITrAC=rA GATGTAAAGA ACAATTACTG ATGrTCAACA 15 TGACTACATA CATAAAGGCG CATGGAGAAA AGTATTGGCC TT1CCATGCAT TAGGTAGTGC TTGTATCAAT TCTTATAGTG GCTAGGGTAT CCTGGAAAAT CT7ACGTGTG GATCATfTCT CAGGACAGTC TAGGACACTA ACGCAGTTTC TCATGFITGG CTTCTA'PTAT TAAAAAATGA TACAATCTCG GGAAAAT1T TTTGATTTTC ATGAAATrCA TGTGTYITC TATAGGTAAC ACAAAITCTG ACTGCTATGA TATGCCTn7G IT=GGAACA G'ITGTCTGCT CTGTACTTGA TATITCACAC ATTGAGGGAG ACA'TTPTC ATCA'TrAAA GCAGGTTATC 20 CATTCTGGGG AGCCATATI1 GTGAGTATAT ATCTATAATr GTrTCTGAAA TAACACTGAA CATAGGTTT TCTC'T7CTC AGATCTAACC AGTTGTTAT TCCCAGTATr AAGATGATAT TTATAATTCT TAA'PTATAAA TATATGTGAG CATATATAAC ATAGATATGC TCATTAACAA CAACAAAAGA TrCTIT1AC AATTAACGGT GGG'AAACA T~AGCCCAC AG=IrATCC CATGAGAAAC CTGAATCTAA TACAAG'TAA ATGACTTGCC TAAGGGCCAC TTGACTAATA GTAATI'GAAC CTAAAC'ITC AGAATCCAAC TCCAGGAACA TACTTCTAGC 25 ACTATTCATC AATAAAGTTA TATGATAAAT ACATACAACT TTATCTGTCA ACTAAAAATA ACAACAGAGG CTGGGCATGG TGGCTCACAC CCGTAATCCC AGCA=rrGG GAGGCTGAGG CAGGTGGATC ACCTGAGGTC AGGAGTITGA GACCAGCCTG ACCAACATGG TGAAACCTCA TCTCTACTAA ATATAAAAAA TTAGCTGAGT GTGATAGTGC ATACCTGTAA TCCAGCTACT TAAGAGGCTG AGGCAGGAGG CTTG TTGAA CCTGGAAGGC AGAGGTTGCA GTGAGCTGAG ATTGTGCCAT TGCACTCCAG CCTGGGCAAT AAGTGCGAAC TCTGTCTCAA 30 AATAATAATA ATAATAATAG AAAATAAAGT TGTC'ITCATG AAAAATGAGG AAAGAGATI'G CTGGGGTGAG AAACA'rrAAG ATCAATGGGC ATATGGTGAC CTTCTATGCC CTAGAAACTC I1TANGGTA TITCTCCTG GTATCTCTTT TACNCATCGT TCTATCTGGA AAAATAGGTG GATGAGTGAG ATAATAACGG TATATAC'ITr TTAAAGGTCT AATTGACATA TATAAATI'GC AAGTAMTCA GATGTCAAT TGCTAACCTT GACACACATA GACACACATG AAAACATCAC CACA117AATA CAATGTATGT ATCCATCA11 CCAAAAGCTT CCCTGTGTAT 35 C=rGTAACT C'ITTC1TCCT CCCTCCACTC C~rGTCCTCT CGTTCCCAAG AAAACAJTGA TCTGCTFTCCT GTGAATATAA ATTAACTTAC ATTTAGA GCTTTATATA AGTATGTTCT CTTACTGTT TGTCT-rCCTT CGCTGCACAG TTATTTTGAG ATTCTI'CAAG ThIT=CTTT ATATCGATAC TTCATTCACA AGAATATAYI' TTAATTCTAG ACTATGTCAC ATTGAC'IMG TCGTCTGCTA AATCC'ITAGT GCTCAGATGA CTTG'PrCAGG ACTCTCCTTG AACCTGTACC TCTGTTANAT TGAAACTTGT CTCTACTGTC TP1TATTTC AAACACAGCT 40 TATTAGGTGT CTCTCAACCC ATCAAACNCA CAATCTGAGT CTITAGGAGA TTGCTTTGAA TTTGTGCTAT TGACTTATAT NTATATNAAA TNTGTAAATG TTTGGTAAAA ATATCATCAT GTACN'IIC ATAATTACGC TATNTNCACA TGATATATGT CAGACTC.TGG AAATATGCAT GCCACAGACA CGTGMICTT GCCTAAAGGG GCTGATGGAA GACNCACATA CNAATAGACG ATTGCAGTAG AATGAGAGTG GTGGTCTAAN CAGTACATGT CCTGATGTTG CTCGGACAGT TACTACNCCA AGAGTACCCC CTGCATTGTC AGGGTrAGCA TCTCCTGGAA 45 GCCTCATGTA AATGAAGAAT TT1CATGCTCC ATCCAGGACC TAATGAATAA GAATCTGCAT 1TTAGCAAGA CCCTCATATG ATTCATATAC ACTTTIT TTTTTITA GATGGAGTCT CACTCTTGTC GCCCAGGCTG GAGTGCAATG GCATGATCYF GGCTCACTGC AACCTCTGCC TCCCGGGT7C AAGTGATIFCT CCTGTCTCAG CCTCCCTAGT AGCTGGGACT ACAGGTGCAT GCCACAGTGG CTGGCTAA'IT 'TT7GTA1Tr TAGTAGAGAC AGGGTTT1CAC CATINTGGTC AGGCTGGTCT TGAACTCATG ACCTCCGGTG ATTCCCCCGC CTCGGCTTCC 50 CAAAGTGCTG GGATTACAGA CATGAGCCAC CACACCCGCC TTAYrCGTAT ACNCATAA TrCTGAGAAG CACTCTATAG AAAATAAGAA TAAGAAAATA 'ITGGGCTCAC AGGTGACATI' AATAAGTAAC TITATCGAGT ACCCCAAA'LT TTACCTATGT TTGGAAGATG GGGTTAAAAG GACACATTGA AAACAAGAAC TCATTGTGGC TI-rfTrCC TCCT=TGA ACAGT1TCT ATITCTGGAA TGTrGTCAAT TATATCTGAA AGGAGAAATG CAACATATCT GGTGAG1TGC CCGTITCTGT CITTGTCCAT CCTTGAAAAG ATAAGAAGAA CAGAGFTTA 55 AGAGTCTTAA GGGAAACACA TCTIGTCTC CTATATTACT TGTGAATGTG GATATATGAT TTTGTTTCAA TCTATTrGT GTCCTAAGGC 'TITGCAAC AGAAGTrGGA TATATCATTA GAAACATAAA TTGTACCATT TAACATACAT GAAGTTrATG TTTACCTTGA CGTTCTTCTA AAAAGTGTCC TACACCGGCA T7GTCCTTGT AGGCATATI'C ACATGATCAA ATAAAATAAT TAGTTCAA TTAAGGAGAA TAT[GAGGA AAGACCGTAC GTGTTCATGT GGTTCCTGAA GGCAGTCCAG TGAGAAAGTA ATATATGCT~r CATrAAACAA TGCGGACATT 60 TTCAGGG'I= CCC'TITAA CCAAAXITTTG GAAGCAATGT GGAATACT GGATGCATCC AGCCCTGAAA TGAAGATAGG LTTATTGAAT GTGCCAGCAA GTGCAGGCCC AGGTCTGAGT GT'FrCATrF AYI7ATCAGGT GAGAGGAAGC CTGGGAGCAA ACACTGCCAG CAGCATAGCT GGGGGAACGG GAATTACCAT CCTGATCATC AACCTGAAGA AGAGC'TrGGC CTATATCCAC ATCCACAGTr GCCAGAAATT TITGAGACC AAGTGCTA TGGCTTCC'IT 'ITCCACTGTA TGTATTT LTrGTGTGGG AAGACTAAGA TTCTGGGTCC TAATGTAAGT 65 AAGAAGCCCT CT-7CTCCTGT TCCATGAACA CCATCCTI= CTGTAACTTC TATITACACAG TATAGTGGTT CTGTAAGTTC ACACAGCCCA GGGAGATGCT GGCTGCCCAC TCCCCTCAAC CCAGGCAAAT TCCTCGGGGT WO 00/62736 PCT/US00/08020 135. TAAAGTTATC TACTGCAAGT GACGATCTCT GGGTITCT GTGCCTGTGT TTGTGTGTGT GTGTGTGTGT GTGTGTGTGT GTATGTGTCA C ITTAAAAGG ACTGGTCAGA TGGTAGGGAG ATGAAAACAG GAGATGCTAT AAGAAAATAA AC'ITGGGG CGAATACCAA TGTGACTCTT =~G1TGTC ATIGTI'GCT GTT1CAATAGG AAATTGTAGT GATGATGCTG YITCTCACCA TTCTGGGACT TGGTAGTGCT GTGTCACTCA CAATCTGTGG 5 AGCTGGGGAA GAACTCAAAG GAAACAAGGT AGATAGAAGC CCGATATAAA ATCTGAATG ACAGGTTAAC GAATTGGAGC =ITTFCC11 AAAATATGGC CTGGG1TMC TGAAACAT1T CTTCCAGAAA ATAGTITCTC CAAGTITAT TAC1TGGT7 TACAAATCTC ACA'ITAAAT CACATITAT ACCATAAGTA GCACACATrT CATAATATTC CTCTGAATGA GGGYTGGGAT AATAGGACTG ATATGTI1AGA AATGCCTTAA AGTGTGTGGA GCATGAGAGA TGGATGTACA GAAGGCTTGT GAGGAAACCA CCCAGGTATC TGGCCTTGPT TTCTGCCCCA 10 GAACTAGCCG CCTATTCCTG T'FrCTGrI'T ATTCC'TIGT TrCTGAC'rr TCC LTCCA ACTTGCTCTA AAACCTCAGT ==C'TCCT TTCTGA'rTCA TGACTACCAA ATGYITCAC TrGCCTCACC CGTCCATTAC ACCTTTGATA AGAACCACCA GACCTTGTGC TCATGTAC IT GCCCATGTCT GATGGAAGAA ACATACTCTC TCCATCTGTC CAC'=CCTG AGGCATTCAA GTCTAGCCAC C'IPAAAAT CACTCTCCTC CAGGCTGGGC ACGGTGTCAC GCCTGTAATC TCAGCAC=E GTGAGGCTGA GGAGGGCGGA TCACTTGAAG TCAGGAGTrC 15 AAAACCAGCC TGGCCAAATG GCAAAACCAA ATCTrC'rrCA ATTATAACCA AATCTTAAAC CAAATCTCTA CTAAAAAATA CAACAAAACA AAACAACAAC AACAAAAACA GAAAAGGAAA CATFAGCCCA GCGTGGTGGC AGGTACCTGA GGTTCCAGAT ACTI7GGGAGG CTGAAGCAGG AGAATCGCTT7 GAGCCCAAGA GATGGAGGTT GCAGTGAGCC GAGATCATGC CACTGCACCA CAGCCAGGGT GACAGAGCCA TACTI'CCCAG CACATTGGGA GGCCAAAGCT GAAGAATAAT 'PTGAGGTGAG GATGGAGA CCAGCCTGGC CAACATGGTG AAACTCCGTC 20 TGTACTAAAA ATATAAAACT TAGTGGGGCA TGGGGGCACA CACCTGTAAT TTCAGCTACT TAGGAGGCTG AGGCAGGAGA AflGCTTGAA CCCGGGAGGC GGAAGTT1GCA GTGAGCCAAG ATCGTGGCCA CTGCACTCCA GCCTGGGTGA CATAGTGAGA 'ITCTGTCTCA AAAAAAATAA AAGAAMTTA AAAAATCACT CTCTFTCCAAA GATAGATAAA TAAGACAGCA GATATACTAA GGAATAACCT CACCAACTTG TCATI1GACTG ACATGA'rfrC rTMGGCCCA C1TGGCCAGC TAGTCTGGTT TGGIT1CTG GAAATGAAAG AAATAATCAG AG'ITAATGA 25 CAGAGAGCGT GAGACCCAGA AAGACAAAAG TAGATGAGGT AAGTCTCTTG AGCGAGACTr CTAGGGATGG GAAATIGTG GTGA TGATA TGAAATGATI' TICCC'ITAT CAGGTTCCAG AGGATCGTGT IFATGAAGAA TTAAACATAT ATI1CAGCTAC TTACAGTGAG TTGGAAGACC CAGGGGAAAT GTCTCCTCCC ATTGAMTAT AAGAATCACG TGTCCAGAAC ACTCTGATTC ACAGCCAAGG ATCCAGAAGG CCAAGGTTTT GTTAAGGGGC TACTGGAAAA A=VCTA FTC TCTCCACAGC CTGCTGGTIT TACA ITAGAT TI'A'TCGCCT GATAAGAATA 30 TITIG'TrCT GCTGCTrCTG TCCACCTTAA TATGCTCCTT CTA'IMGTAG ATATGATAGA CTCCTATTr TCTrG='TA TAUTATGACC ACACACATCT CTGCTGGAAA GTCAACATGT AGTAAGCAAG AITJ7AACTGT TTGATTATAA CTGTGCAAAT ACAGAAAAAA AGAAGGCTGG CTGAAAGI17G AGTrAAACTT TGACAG'ITTG ATAATATTG G FTCTrAGGG TflTITT TIAGCATT CTTAATAGTr ACAGT-rGGGC ATGATIrTGTA CCATCCACCC ATACCCACAC AGTCACAGTC ACACACACAT ATGTATFACT TACACTATAT ATAACTTCCT 35 ATGCAAATAT TITACCACCA GTCAATAATA CATPI1GCC AAGACATGAA GTMVATAAA GATCTGTATA ATTGCCTGAA TCACCAGCAC ATTCACTGAC ATGATATTAT TTGCAGA'TG ACAAGTAGGA AGTGGGGAAC TTATTAAG TrACTCGTrG TCTGGGGAGG TAAATAGGrT AAAAACAGGG AAATTATAAG TGCAGAGATT AACAMFCAC AAATG'TrAG TGAAACA'ITT GTGAAAAAAG AAGACTAAAT TAAGACCTGA GCTGAAATAA AGTGACGTGG AAATGGAAAT AATGGTI'ATA TCTAAAACAT GTAGAAAAAG AGTAACTGGT AGATMTGTT 40 AACAAK[TAA AGAATAAAGT TAGACAAGCA ACTGGTGAC TAATACATTA AGCGITTTGAG TCTAAGATGA AAGGAGAACA CTGGTTATGT TGATAGAATG ATAAAAAGGG TCGGGCGCGG AGGCTCACGC CTGTAATCCC AGCCCTTTGG GAGGCCGAGG TGGGCAGATC ACGAAGTCAG TAG=~GAGA CCAGCCTGGC CAACATAGTG AAACCCCGTC TCTACTAAAA ATACAAAAAA AAAATTAGCT GGGTGTGGTG GCAGTCACCT GTAGTCCCAG CTAC'GGGA GGATGAGGCA GGAGAATCGC TTGAACCTGG GAGGCGGAGG T-rGCAGTGAG CCGAGATCGC 45 ACCAGTGCAC TCCAGCCTTG GTGACAATGG GAGACTCCAT CTCAAAAAAA AAAAAAAAAA AAAAAAGATA AAAAGTCAGA AATCTGAAAA GTGGAGGAAG AGTACAAATA GACCTAAATT AAGTCTCAT7TTTT~GGC'rrT GATITTGGGG AGACAAAGGG AAATGCAGCC ATAGAGGGCC TGATGACATC CAATACATGA G117CTGGTAA AGATAAAATT TGATACACGG ITTGGTGTCA TrATAAGAGA AATCATrATT AAATGAAGCA AGTTAACACT CTAAGAGAAT TATI=GAGA TAGAAGTGAA GCTAAGCTAA AC'ITCACATG CCTATAAUTG GAGGGAAAAA 50 CTAAGGATAA AATCTAGCCT AGAAGATACA ATAATrAGTC ATAAACATGC A'ITGTGAAAC TGTAGAGAGC AGGTAGCCCA AAATAGAGAA AGATTAGATA AAGAGAAAAT AAGTATCCAT CAGAGACAGT ATCTCTAGGC TrGGGCAAGA GAAAAGTCCA CAGTGATAAG CAACTCCACC TAAGGCATGA ATATGCGGCA GAGAAAACAG CAATAGTGAA TGAATGCAAA AGGTGCTGAG CAAATrCCAC ACATGAGTAT TGTGCATGAG TAAATGAATA AAACATGC AAAGACCTTT AGAGAAAGAG AATGGGAGCA TATGTGCGAA ATAAGATAGT TGATTATGAA 55 TAGAAGGTAG TGAAGAAAAG CAAGCTAAGA AAAAATTCTG TTTATAAAAG AAGGAAAAGA TAGMIIATGT T=TAGCCTA AGTATAAGAG TCCTACAGAT GGACTGAAAA AAATCAGTCT GAGAGTA'ITA GTCACAATTA ATGAAATAAT TACA'ITAT GTATTGAGGA TGCCAAGAT-r AAAAGGTGAC AGGTAGATGT TANITCCCT AGATTGTGAA AGTGATCACG ACAATCACAC AACAAATAAT TAAGTGACTT GGTATGC'TrT A'PTTAATTGT AGGGCCTGAG GTITCCATT CTCATI=rC TAAAATACAA TI=G1CT CCAAATTTGA CAGCAGAATA 60 AAAACCCTAC CCTI1CACTG TGTATCATGC TAAGCTGCAT CTCTACTC1T GATCATCTGT AGGTAYTAAT CACATCACTI7 CCATGGCATG GATGTrCACA TACAGACTCT TAACCCTGGT 'I1ACCAGGAC CTCTAGGAGT GGATCCAATC TATATCTTIA CAGTrGTATA GTATATGATA TCTCTITAT TrCACTCAAT TTATATTC ATCATTGACT ACATAITCT TATACACAAC ACACAAMIIA TGAA TTr CTCAAGATCA TTCTGAGAGT TGCCCCACCC TACCTGCCT7 TTATAGTACG CCCACCTCAG GCAGACACAG AGCACAATGC TGGGGTTCTC 65 TTCACACTAT CACTGCCCCA AATTGTCYI7 CTAAAT17CA ACTrCAATGT CATC117CTCC ATGAAGACCA CTGAATGAAC ACC'TTTTCAT CCAGCCTTAA 'TrCFGCTC CATAACTACT CTATCCCACG ATGCAGTAYI? WO 00/62736 PCT/USOO/08020 136 GTATCAFTAA TrATTAGTGT GCTTGTGACC TCCTrATGTA TTCTCAAT7A CCTGTATITG TGCAATAAAT TGGAATAATG TAACTTGA'F[ TCTTATCTGT GTrTGTG'rrG GCATGCAAGA 'FTrAGGTACT TATCAAGATA ATGGGGAATT AAGGCATCAA TAAAATGATG CCAAAGACCA AGAGCAGTTT CTGAAGTCCT CCTITCATC AGCTCTTTAT CAAACAGAAC ACTCTATAAA CAACCCATAG CCAGAAAACA GGATGTAGGA ACAATCACCA 5 GCACACTCTA TAAACAACCC ATAGCCAGAA AACAGAATGT AAGGACAATC ACCAGCCATC TI'TGTCAAT AATTGATGGA ATAGAGTTGA AAGGAACTGG AGCATGAGTC ATATITGACC AGTCAGTCCT CACTCTTATT TACTTGCTAT GTAAAC'I1GA GAAAGCTIT TTCTCTTTGT GAACCTCAGG T1TACATCT GAAAATGAGA AATrTGGAAC AAAAGATTCC TAACTGGTCT FrCTGTrCCC ATATTCTGTG ATITPCAAT A=~AGGATT TTGGTAATC ACAATTACTT AGTITGTGGT TGAGATAGCA ACACGAATCA GAACTATrG GTGGACATAT 10 'ITCAAAGGA GTAGCTCTCC AC1TrGGGTA AAGAAGTGAT GCNGGTCGTG GTGGCTCACG CCTGTAATCC CAGCAC'ITTA GGGAGGCCAA GGCGGGTGGA TCACGAGGTC AGGAGATCGA GACCATCCTG GCTAACACGG TGAAACCCCG TCTCTACTAA AAAATACAAA AAATrAGCCA GGCGTGGTGG CGGGCGCCTG TAGTCCCACG TACTCGGGAG GCTGAGGCAG GAGAATGGCA TGAACCAGGG AGGCGGAGCT TGCCGTGAGC CGAGATAGCG CCACTGCAGT CCCTCCTGGG CAAAAGAGCA AGACTGCGTC TCAAAAAAAA AAAAAAAAAA AAAAAAAGAA 15 GTGTGTGGAG TAGCAGGACA CCTGCAACAA TAATATI= CTAAATCCCT CTGAAAAATG CTAATCAAAG GGTTTTC CTAAAAA117G TC'rTAGAAAT AAAKTCCC CI=GGGAGA CCGAGGCTGG CAGATCACGA GGTCAGGAGA TAGAGACCAC GGTGAAACCC CGTCTCTACT AAAAATACTA AAAATTAGCC GGGGNGTGGT GGTGGGTACA CCTGTAGTCC CAGCTACTTG GAGGCTGAGG CTGGAGAATC ACGTGAAC-3' (FRAG. NO:_)(SEQ. ID NO:2505) 20 5'-AACAAGAAAA GCG'ITGGTAG CTCTGGTGAA TCCCAAAAGA ATGTGGCAGT TGCTAGCCAT GCTCCTGAAT ATGTATAAAC AGTACATCAT ATGACTAAGA GTrFGACTTA GGGGTTAGAT TFATGTGTr TGAACCCCAA ATTAGTFTA~r TAATAGTTGG CACCCCAAAA CAAGTTAC'IT AACCTCACTA AGGTTCAGTT TrCCTG1TTA TAAAATGTAG ATAGTGATAG TATGTAC'ITT ATAGGAYL'AT TGTGAAAAAT AAATGAAATA TCAGATAT TTAGGATAAC ACCTGGCATA TG1TIGGTAT TCAGAAY7AG TTGCTGCTGT T'ATTCTGC TCTCCCTTGC 25 ATCCCACYPT TCTAAG'rrGT AAACTAAATA GTTGTACACA GATrGACAGA TI'AAGAAAGG CTTGTGATTG TGCTAGACCT ATGCCTATGC CTCTGTCTCA CCAGATTCCA GGTGTATATG TGGAGGTGGG ATAGGGAGTG GAGTAAGTGG GTAAATATTA AATrGCCCAG TTGGGCACCA TCCTGAATAT TATCTCTAAA GAAAGAAGCA AAACCAGGCA CAGCTGATGG GTTAACCAGA TATGATACAG AAAACATTrC CTTCTGC'T TTGGTrTAA GCCTATATIT GAAGCCTI'AG ATCrCTCCAG CACAGTAAGC ACCAGGAGTC CATGAAGAAG ATG-3' (FRAG. 30 NO:_)(SEQ. ID NO:2500) 5'-GATCTTCATG TGGAATGACT GGITCA11C AATAGAC'ITA ATTCAGCAGT CTGTGGGGAA GAGCAAGGTA TGATAGAATG G'rrCCTCAAG TGCTTCAGAT GTGAAGTGGG TITAAATATA CTGTCCCTGT C'rrCTTCAGA GYITGGTAA AGATAAAATA GGACACTCAT 'PTAAAAGCAA TCITGCAAA TGACAAGCCA CTATAGACAT TAATAGAGTI' FCATrTCCA GTATI'ATCAT TAATATCAGA TCCTGGAAGA AGGTrGAGCC FTGACCTAGA 35 GCAAAAAAAC AGAAGAATTA GTAAAGGAAT CCTGGAGAAA GCCCCTGCTG TGTAYITAAA GGAGAAAGGG AGATCATGTT GGGAAATTAT AATATTAAAA GTAAACAAAA GCTAGGAAGT AAAATAAAAT AAATTATATG GCCTAGATCC CCATAAGTAA TGGnI7AACT TCTGCCT7CC TGTGITFCTGA GCCAGATTAG GGCACAGTAG AGAAAGAGGA GTCTCTGAAA ATGTT7CCAA 'I=CGCTGGT CAGACAGCGG ATCATCAGTG AATCAGATGA AAATTGTGG AMATGCAC TAACTGATCA GCAGGAAATr AAACAAGAAA AGCGITrGGTA GCTCTGGTGA 40 ATCCCAAAAG AA'ITTGGCAG TTGCTAGCCA TGCTCCTGAA TATGTATAAA CAGTACATCA TATGACTAAG AGTTGACTI' AGGGGTTAGA 3T=ATGTGT 'VrGAACCCCA AATrAGTTAT ITAATAGT1'G GCACCCCAAA ACAAGTTACT TAACCTCACT AAGATTCAGT 'ITTCCTGTTT ATAAAATGTA GATAGTGATA GTATGTACTTr TATAGGATTA TTGTGAAAAA TAAATGAAAT ATCAGA'IMA TITAGGATAA CACCTGGCAT ATGTTTGGTA TTCAGTAAT7 AGTTGCTGCT G=T]YICT GCTCTCCCT7 GCATCCCACT TITCTAAGTr GTAAACTAAA 45 TAGTTGTACA CAGATTGACA GA'rTAAGAAA GGCTTGTGAT TGTGCTAGAC CTATGCCTCT CTCTCACCAG ATTCCAGGTG TATATGTGGA GGTGGGATAG GGAGTGGAGT AAGTGGGTAA ATATrAAA'T GCCCAGTTGG GCACCATCCT GAATA'FTATC TCTAAAGAAA GAAGCAAAAC CAGGCACAGC TGATGGGTTA ACCAGATATG ATACAGAAAA CATTTCCTTC TGCTITIGG =FTAAGCCT ATA IMGAAG CCTTAGATCT CTCCAGCACA GTAAGCACCA GGAGTCCATG AAGAAGATGG CTCCTGCCAT GGAATCCCCT ACTCTACTGT GTGTAGCC'r 50 ACTGFFCTTC GGTAAGTAGA GATT1CAArrA CCCCTCCCAG GGAGGCCCAA ATGAAITTGG GGAGCAGCTG GGGTAGGAAC CTTTACTGTG GGTGGTGACT TM~CTAGGA CATGTGCAAA CTATTGGGCA ITFCCCAGGG ACTCTGTAGT GGAGCCAAGC TAGAAAGCAG AGGCAAGTGG GCTGAGCAAC ACCTAAGGAG GAAGCCAGAC TGAAAGCTI'G GTTCC'rTGCA ITTGCTCTGG CATCT~rCCAG AGTGCAAATI' TCCTACCAAG GTAATGAGGG TAGAGGAGAG AAAGAAGCTC TI1TCTT1CCCC TGA'ITCTCAT TCCTGAAAAG ACGGTTGGTC CTTAAAA'rrC 55. CATGGATGTA GATCTTATCC CCACACCCAG ATTCTAGTCC TCTGGAGATA AAGAAGACTG CTGGACACTA ATGTATCCTC TCTGGACTIT TGCAGCTCCA GATGGCGTGT TAGCAGGTGA GTCCTCTG11 CTTGTYrCCCT TGGTGTATCA ACATGTCTGG GCA'TrGC'ITT CCTCTCACTA 7TICTTCGT CCCATCAc117 CTGC'ITrCTA ATGAGCATGA ATCTGYrCCT TGGCCAGACT A='~CCCTC TCCACCTTGC CTTGTC'TrTC TT CCC TGATTCATTG CATTCTCTCA AGTCA~rCTC TCCTCTGTTT TAGTCAATAA CCATGTCTGT TGCACATATA 60 CATGTCTCAT TCTCTCTCCT AGACAGTTG GCATGATCTC GCTCAATAAT TACATTA'TA YrATT1ArrGC CATITTTATAA ITGAGGATGC TGAAACTCAG TGA'IrCTG GTGGTFACAT GGCTAAGGAA CTGGATrCA ACGTAAGTI7C CTTGGATCTA AGTCCAGTTC TCTTCTGACT ATATCACCCT TTTGTTATCA CCATGTATCT ACTTCTIT7GG TCTCTGTrCA AA'IMGCACT ACATCCCC'IT GTrCCAGGAA GCCATTCAAG ACTGACTTTC TJ7AGTGCCTC TCACTACT= CTGGAACTGA CATATGTnT TCACTCTGTA TATACTTACA AITAAATAGT 65 CATAAATATT CAGAGC'ITGG AGAAACCTTA TA'IMCATCC AGTCCAGTAA ATrATCCAT CCATAA'FrCA WO 00/62736 PCT/USOO/08020 137 CTCATTCATT CACATAATAA ATATTAATG TAACAATGGT TGAACATGGC AGACAGTGTT TCTACCTCAA AAGAGATTGC AGTCCTCATT TACAGATACT GAATTGAAAT TAACAGAAGT AGAGTGAGTC AGCTCAAATC ACATAGTGAA TTGGTTTCTT TGTTTTTAAA TCTCCTGCAT ATGTGTCCTG TCTTTCTCCC TGTGTTGGGC GTTCCCTGGG GCACCAATAC TAATTrCTCC TTCCCCTAGA AATCAAAACA GGGTCTTATC ACCAACAGAA 5 TAAGGACAGG TTGACCACTG ATTGTCAGAA TATTGCTTCG TTTGTACTTT TAAGCCTAGA CAGTTTTCAA TGACTTTTTT TCTCTCTACA TGTCTTTTCA TATTTTTATC TTCTTGAAGT CCCTCAGAAA CCTAAGGTCT CCTTGAACCC TCCATGGAAT AGAATATTTA AAGGAGAGAA TGTGACTCTT ACATGTAATG GGAACAATTT CTTTGAAGTC AGTrCCACCA AATGGTTCCA CAATGGCAGC CTTTCAGAAG AGACAAATTC AAGTTTGAAT ATTGTGAATG CCAAATTTGA AGACAGTGGA GAATACAAAT GTCAGCACCA ACAAGTTAAT GAGAGTGAAC 10 CTGTGTACCT GGAAGTCTTC AGTGGTAAGT TCCAGGGATA TGGAAATACA GATCTCTCAT GTGAGGGATG GCTCATCTGA AGATGGGAAA AAACAGGTrA TTCCAAGGGT TAGGACACCA GAGTGGGATT CAAGGCCTCT CATTTTTAAG ACCCCTGCAT TGGCTGGGCA CAGTGGCTCA CGCCTGTAAT CCCAGCACTIT TGGGAGGCTG AGGCAGGTGG ATCACGAGGT CAGGAGATCG AGACCATCCG GCTAACATGG TGAAACCCCA TCTCTGCTAA AAAATATATA TATATAAAAT TAGCCGGGCG TAGTGGTGGG CACCTGTAGT CCCAGGTACT CGGGAGGCTG 15 AGGCAGGAGA ATGGTGTGAA CCCAGGAGGT GGAGGTTGCA GTGAGCTGAG ATCACGCCAC TGCCCTCCAG CCTGGGCTAC AGAGCAAGAC TCCGTCTCAA AAAATAAATA AATAAATAAA AAAGACCCCT GCATCTCTTT TCTTCTACCC CCTTCCCTTT TGATTACTTG TATGCCTTCT TTCAATATTC TAGTCATCTC TCAATATTAT TCCTCCACCC TATTTTCCTC TATCTTTCT GCCTAGATTC AGGTATATAT TATGTGGTCA AACAGCATGA CATATATGTG AACATTTCAA AGAGCTGTGT ATCTGGAATA GGATCAAAAG GTTTGACTTA AAGTTTTGCT 20 CTGCATAATC CATATGGCAG GACCTGAATA TTAGGTTGTA CTCTTCGTTA TGAAACATAT CTGGGTACAT TTCCTTATGT CCTCTGTTGT TACTTAAGAA CACATATTTC ATGCTTGTTT CATTTTTATC ACTCCTACTG CCAACAAATA GCATAGCATG CTTAGGCACA TGTGGCTTAA TTAGCAAATG TTGAATAAAC AAATTAATGA TITGAATAG TGACCAATAG GTCTCTTTTA TACTCTATAT TTTTCTCTTG AGTGAAAAAA AATGTTTCAA CCTCCATATG TAAATTCCAA ACACAAACTA AAGCAATGTA GAATAGCTTC TTTATTCCCT GGAGTAGGTT 25 CTAGAGAAGT CCTAAAGGAT TGGTCCTAAA TTAATTATGC TTATTATGCT AGCGATATTT CCTTTCAAAA T'rCTCCTTTA ATGAATGCTT TTTAATTTTT ACAAAAGCAT TAACCATAGA ATGTGATTCT TGTCTTTCAC TGACTCATTA GTGACAAATA TTTGTTGAGT ACCTACCAAC TCCTAAGTAT TGCTACCAAC TCCTAAATAC TGTGTTGGGC ATTCAGAATA GAATGTAGAA CTAGACAGGG TCCCTGACTT CTTGGAGCAC AGAGCAGTAT GGGAAGAGGA CATTAAATAA AGAATTACAT AAGTAATTAA TTTAAATTAT ACATGTTTTG AAGAAGTTTT 30 TTTTTGACAA CTATAATTAA CACTAGAACT GGGAAGTTTC TATAAGGTAA GAGAGGACAA AATAGACACT CTCCTAAGCT AAAATTCCCA AGAAAGACTG TTTATTTTCC CCTAACTAAC TAGAACTAGC AACAGAAGAT CTGAAAGGAA TTCTGGCTTT CAAGTGTTCC ATGTATGGAC TCATCAGGGA GGTCCGAGAG GCTTTGTGGC CCCAGACTGA CTTTTCAGGA GGGGAAAGGA T17ATCAATA CACAAGACAG GCTCTAAGCA TTATTTTGTG CCCTTTAAAA ATCCACTTTA TGAGCCAAAA AGTGAGTTAA TGATAATTCA TAGTTTCTGA CACATGCTCT 35 ATGCGTGGCT CTCTTTTCTC TATTCATTCT CTCTCTCTTC ATTTATTGTT AAATAAATAA TGTAATGAAT GTTCTTCAGA CTGGCTGCTC CTTCAGGCCT CTGCTGAGGT GGTGATGGAG GGCCAGCCCC TCTTCCTCAG GTGCCATGGT TGGAGGAACT GGGATGTGTA CAAGGTGATC TATTATAAGG ATGGTGAAGC TCTCAAGTAC TGGTATGAGA ACCACAACAT CTCCATTACA AATGCCACAG TTGAAGACAG TGGAACCTAC TACTGTACGG GCAAAGTGTG GCAGCTGGAC TATGAGTCTG AGCCCCTCAA CATTACTGTA ATAAAAGGTG AGTTGGTAAA 40 GGAAAGGAAA AGCATCCATA GCAGGGGAAG GAAGAGAGAA CTTCTGAGCC TGAGCAGTTG CAGCTTGTAG AAGGGGGGCA CCTGTGATAC ACTGGAAAGC CTACCAGACT TGCAATGAGG AGACCTGGGT GATAGTATAT ATCTCAATCT CTGTTTCAAA GCCTTGACTT GTTAAATGGT GATAGTAATA CCTGCTTGCA CTATGAAATT TTTATGAAGA TTAATGTGGT AATATTTGTG AAATGACTTT GTAAACTGTT AAGCACTACC CAAGCATAAC AGATTGTGAT TACTATTTTG ATCTCAAAGT CATCTGTTGC TCCTGGGGGA ACACTTATAT TTATCAAATT 45 GAAAAAAAGT TTCAAAGTTG AATGAAGAAA GGATATAAAG AGCTTGAGGA GCCCATTCCA GCTTAGGAGG GCTGGGAAAG GAAACCAGCA AGTCAGTAAG CTGTGTGCCT GTGTATTGAG GGAGGAGGGA ATGGACTTGA TATGGAGAGG GTAGGGAGGT GGACTGCCTC TATGGCCTGT AAGAAAAACT GCTCTCTCCA AACTCTTTAT AAGAGAGGGA GCCTGTGAAG TATTCACTTT TGAAGGAGAA AGTTAGACTT TTCCTTCACA CACTTTGTAC ATAATAATGT TTAAAAAAGC ATGAGGTCAA AATACATAAT TAAGTCCTAG CAGTCTCTG TrAACTAATT 50 TGAGACTGAA GTGCTATGTA CTTGTCTCTA GGCTTCCAGT ATCTTCATCT GTAAAACAGA ATATTGGTC TAGATTCCAT TAGAATCATT TGATAACTTA AAAAATATAT TGATGCTCAT GTCTCATTTC TTGAGATTCT GATTTAATTG GTTTGGGGTG CAGCCTGGGT ATACGTATT TTCATAGGTC TTTCACATAA TGGTAATGGG TAGCCAATAT TGAGAATCAC TTGTCTAGGT GATCTTTAAA TGATTTCTGG ATGTAATATT CTGAGGCTCT ATAATTTGAG ACTAATCACA AAAATCGGTA CAGTTTATAA ACAGACTAAC AGAACCACAA AATAATAGAA 55 TTGGAAGGCA ATTTAACTAG TGCAATTTCT TCATTTTGCC TAACAGGCAT GTAAGAAATG ATGATTGATT GAGTAATAGG CATTGATGAC CCCTGTCCTC ACTTTGTCCC CTTTCCACCC CTTAATTATA TGTGAATTCT GGTCTTGTCA TTTCGAATAA GGGGTATC TTTCCTATTG TCTTCCCCTC TGGGCACGGC ACACTGGCTA CTGGAGTTAA GAGGAAATGC TTAGGACTCC CTGTGGCTCC AGGGAGCACC AACAGAGCAA CTCAACCTAG TGTTAATCTG AGTGTTTTCT CTGTGCTTCT GGATGCCACA TCACGCTAAA AATGAAGGAC AAAGCTTGGT 60 CTTTCTCTTA GGGAGGATGA AACTCTGAAC CTCATTTTTC AGTTCCCAAG ATGAATTATG TTTCTCATTG CATCTGTGTT CCACTACAGC TCCGCGTGAG AAGTACTGGC TACAATTTTT TATCCCATTG TTGGTGGTGA TTCTGTTTGC TGTGGACACA GGATTATTTA TCTCAACTCA GCAGCAGGTC ACATTTCTCT TGAAGATTAA GAGAACCAGG AAAGGCTTCA GACTTCTGAA CCCACATCCT AAGCCAAACC CCAAAAACAA CTGATATAAT TACTCAAGAA ATATTTGCAA CATTAGTTTT TTTCCAGCAT CAGCAATTGC TACTCAATTG TCAAACACAG 65 CTTGCAATAT ACATAGAAAC GTCTGTGCTC AAGGATTTAT AGAAATGCTT CATTAAACTG AGTGAAACTG WO 00/62736 PCT/USOO/08020 138 GTTAAGTGGC ATGTAATAGT AAGTGCTCAA FrAACATrGG TTGAATAAAT GAGAGAATGA ATAGATI'CAT TrATrAGCAT TTGTAAAAGA GATG ITCAAT TTCAATAAAA TAAATATAAA ACCATGTAAC AGAATGC'rrC TGAGTATTCA AGGCTTGCTA GTTTG TI'GT T-rG=rCTA CTAAAGGCAA GGACCATGAA GTrCTAGAT7 GGAAATGTCC TCTC'ITGACT AFTGCAAGTG CGATCTAGGA ATGAAAAGAC ATAGGAGGAT GCCAGTGAGG 5 TGGATCA'ITT T7ATGCTTCT TCTI7CAGC'IT ACTAAATATG AACTITCAGT TCTTGGCAGA ATCAGGGACA GTCTCAAGAC ATAGGACTCT CAGGATGAAG TAGAGTCCAG GATTCCTCTG TGATTGTn' GCCCCTCCCA AATTTATATC 'VrGAACTI7AT GTCTTGTATC 'FrTATACAGC ACCTGAACCA AGCA'FT]GG AGAAATTCCA GCTAATAATA ATAACCAAAA CC'I7CGGCTC TGAAAACAGT CCAGGACTGA ATAAGATCTT GGGCAAAAGA ACTAGACAGT T[TGG'TrTAT 'ITTCCCn7TC A'rIMATGTC TTCATCATAG TCATTGGAGG CTCATTCT7C 10 TTGTCATGGA GTAAATGGGA TI7AAAGlC-3' (FRAG. NO:_)(SEQ. ID NO:2501) 5'-TACTAAGAGT CTCCAGCATC CTCCACCTGT CTACCACCGA GCATGGGCCT ATATGAAG CCTTAGATCT CTCCAGCACA GTAAGCACCA GGAGTCCATG AAGAAGATGG CTCCTGCCAT GGAATCCCCT ACTCTACTGT GTGTAGCCTr ACTG'rrCTTC GCTCCAGATG GCGTG'ITAGC AGTCCCTCAG AAACCTAAGG TCTCCTTGAA CCCTCCATGG AATAGAATAT TTAAAGGAGA GAATGTGACT C1TACATGTA ATGGGAACAA 'IrCI=GAA 15 GTCAGTTCCA CCAAATGGTT CCACAATGGC AGCCTTTCAG AAGAGACAAA TrCAAG'TrTG AATATTGTGA ATGCCAAA317 TGAAGACAGT GGAGAATACA AATGTCAGCA CCAACAAGTr AATGAGAGTG AACCTGTGTA CCTGGAAGTC TJCAGTGACT GGCTGCTCCT TCAGGCCTCT GCTGAGGTGG TGATGGAGGG CCAGCCCCTC TTCCTCAGGT GCCATGGTTG GAGGAACTGG GATGTGTACA AGGTGATCTA TTATAAGGAT GGTGAAGCTC TCAAGTACTG GTATGAGAAC CACAACATCT CCA'ITACAAA TGCCACAGTT GAAGACAGTG GAACCTACTA 20 CTGTACGGGC AAAGTGTGGC AGCTGGACTA TGAGTCTGAG CCCCTCAACA TTACTGTAAT AAAAGCTCCG CGTGAGAAGT ACTGGCTACA ATTTITTATC CCA'rrGTTGG TGGTGATTCT G'TrGCTGTG GACACAGGAT TATTATCTC AACTCAGCAG CAGGTCACAT 'FrCTCTTGAA GATTAAGAGA ACCAGGAAAG GCITCAGACT TCTGAACCCA CATCCTAAGC CAAACCCCAA AAACAACTGA TATAATTACT CAAGAAATAT TrGCAACA'rr AG'TI1TI7C CAGCATCAGC AATTGCTACT CAATrGTCAA ACACAGCTTG CAATATACAT AGAAACGTCT 25 GTGCTCAAGG MTTTATAGAA ATGCTrCA'rT AAACTGAGTG AAACTGGTTA AGTGGCATGT AATAGTAAGT GCTCAATTAA CTrGGTI'GA ATAAATGAGA GAATGAATAG ATrCA'TI'AT TAGCATTGT AAAAGAGATG TrCAATTTCA ATAAAATAAA TATAAAACCA TGTAACAGAA TGCTTGTGAG TAAAAAAAAA AAAAAAAAAA AAAAAAAA-3' (FRAG. NO:_) (SEQ. ID NO:2502) 5'-TCTCAATATA ATAATATrCT TrATTCCTGG ACAGCTCGGT TAATGAAAAA ATOGACACAG AAAGTAATAG 30 GAGAGCAAAT cT-rGCTCTCC CACAGGAGCC TTrCCAGTGTG CCTGCAMTG AAGTCTJ7GGA AATATCTCCC CAGGAAGTAT CTTCAGGCAG ACTATTGAAG TCGGCCTCAT CCCCACCACT GCATACATGG CTGACAGTTT TGAAAAAAGA GCAGGAGTTC CTGGGGGTAA CACAAATTCT GACTGCTATG ATATGCC =T GTTTTGGAAC AGTTGTCTGC TCTGTACTTG ATATrTCACA CATTGAGGGA GACATTT CATCA'ITAA AGCAGGTTAT CCATTCTGGG GAGCCATATT TT1TCTATT TCTGGAATGT TGTCAATrAT ATCTGAAAGG AGAAATGCAA 35 CATATCTGGT GAGAGGAAGC CTGGGAGCAA ACACTGCCAG CAGCATAGCT GGGGGAACGG GAATTACCAT CCTGATCATC AACCTGAAGA AGAGCTT1GGC CTATATCCAC ATCCACAGTT GCCAGAAATT T=GAGACC AAGTGCTITA TGGCTTCCTT TTCCACTGAA ATT7GTAGTGA TGATGCTG'rT TCTCACCATT CTGGGACrrG GTAGTGCTGT GTCACTCACA ATCTGTGGAG CTGGGGAAGA ACTCAAAGGA AACAAGGTTC CAGAGGATCG TGYI1'ATGAA GAATTAAACA TATATTCAGC TACTTACAGT GAG'rrGGAAG ACCCAGGGGA AATGTCTCCT 40 CCCATTGATT TATAAGAATC ACGTGTCCAG AACACTCTGA ITrCACAGCCA AGGATCCAGA AGGCCAAGGT CTTGTTAAGG GGCTACTGGA AAAA'1TTCTA 'ITCTCTCCAC AGCCTGCTGG 1T11-3'(FRAG.NO: )(SEQ.TD NO:2503) 5'-AAGCTITCA AAGGTGCAAT TGGATAACTT CTGCCATGAG AAATGGCTGA ATTGGGACAC AAGTGGGGAC AATT1CCAGAA GAAGGGCACA TCTCTT' TIX2TGCAGI1' CTTTCTCACC Tr1CTCAACTC CTACTAAAAT GTCTCATT CAGGTTCTGT AAATCCTGCT AGTCTCAGGC AAAATTATGC TCCAGGAGTC TCAAATI=C 45 TTA1TTCATA TTAGTCTTTA TTTAGTAGAC TFrCTCAAMT TTCTATTCAT CACAAGTAAA AGCCTGTFGA TCTTAATCAG CCAAGAAACT TATCTGTCTG GCAAATGACT TATGTATAAA GAGAATCATC AATGTCATGA GGTAACCCAT TTCAACTGCC TA ITCAGAGC ATGCAGTAAG AGGAAATCCA CCAAGTCTCA ATATAATAAT ATTC TrA'T CCTGGACAGC TCGGTTAATG AAAAAATGGA CACAGAAAGT AATAGGAGAG CAAATCTI'GC TCTCCCACAG GAGCCTTCCA GGTAGGTACA AGGTATT1ATT TIT=CTACC CTCAGTCACT TGTGGCAGGG 50 GAAGTCATAG TCACGGTGCT TAGGAGATGA AACTrTTfG ATrFAGGCAT GGATCCATCT AGTTrAATrA ATATATTGGG TATGAGGAAG CTACTTGCTG TACT=CCAT GTGGTTCTCT CTCCCTGGAG AGGAACATT TTACTCAGCT TGCAAACTGG AAATAGATTT TCTCACATrA GAAGCTCAT7 'TCTGGGTAT GAGACAGGAG AGTTCATACT GTGTATGTAG ATCTCTGGCT TCTGGGTCTG ACATGTGCTG AGGGACACAT ATCCTTCACA CATGCTTTTA TAAATACTI1G ATAAAGTAAC CTGC'CTrTG ATTGGTC'rI7 ATAATCCATA AGCTGTGGGA 55 TGCTrFCTCTG AAGATGAAAA TAGTAATAGA GTCCCATCTA GCTA TTCAAA GCCA'I17ccTr CATrGTAT-rc TGTGCACATG AAGTTGGGGT 'TFG~rACTGA CAAAATATAT TCAGATACAT TTCTATGTrA AAAGGATTGT GAGATGCATA GGTAAATGTG TTTA'TTTCA G=rrAC=G TCAACATAGA TGAATGAGAA AGAACTTGAA AGTAACACTG GATTAAGAAT AGGAAAATI1T GGCATGGATr 'TGCTCCA'rr TTGTCCCATC TAATCACTTG GATAGTGTTC AGGTGT-rCTL' GGTCAGTTAC TTGGATGCTC TGAGC'TrTAG TTCTTGGTG ATTACAATGA 60 AGATTrGAAT TACAGGATGG CTITGAAAAA ATAAACAAAA CTCCCC'TC TGTCTGTCGA GAATG I1GCA CAGGGAGTTA CAGAATGTTC TCATGACTGA ATTGCYTFA AATTTCACAG TGTGCCTGCA TTTGAAGTCT TGGAAATATC TCCCCAGGAA GTATC'ITCAG GCAGACTATF GAAGTCGGCC TCATCCCCAC CACTGCATAC ATGGCTGACA GTITGAAAA AAGAGCAGGA GTTCCTGGGG GTGAGTGAGC CTCCTCCAAC TT7GACTAGA GTAAGGGTTG GGTCTAGAAA AGAATATTGA GTTGCATCAA CTGITPCCC ACTTGGATTC ATGAGAGGTG 65 T-rAGGTCCTT TAAAAAACAT GGTAGATAAA GAGTTGACAC TAACTGGGTC CTTTTGGGAA GAGCCAGAAG CAMFCCTCA TAAAGACTTT AAATTGCTAG GACGAGAATG GCCAACAGGA GTGAAGGATT CATAACTITA WO 00/62736 PCT/USOO/08020 139 TCTTTACTTA GATGTAAAGA ACAATTACTG ATGTTCAACA TGACTACATA CATAAAGGCG CATGGAGAAA AGTATTGGCC TTCCATGCAT TAGGTAGTGC TTGTATCAAT TCTTATAGTG GCTAGGGTAT CCTGGAAAAT CTTACGTGTG GATCATTTCT CAGGACAGTC TAGGACACTA ACGCAGTTC TCATGTTTGG CTTCTATTAT TAAAAAATGA TACAATCTCG GGAAAATTTT TTTGATTTTC ATGAAATTCA TGTGTTTC TATAGGTAAC 5 ACAAATTCTG ACTGCTATGA TATGCCTTTG TTTTGGAACA GTTGTCTGCT CTGTACTTGA TATTTCACAC ATTGAGGGAG ACATTTTTTC ATCATTTAAA GCAGGTTATC CATTCTGGGG AGCCATATTT GTGAGTATAT ATCTATAATT GTTTCTGAAA TAACACTGAA CATAGGTTTT TCTCTTTCTC AGATCTAACC AGTTGTTTAT TCCCAGTATT AAGATGATAT TTATAATTCT TAATTATAAA TATATGTGAG CATATATAAC ATAGATATGC TCATTAACAA CAACAAAAGA TTCTTTAC AATTAACGGT GGGTTAAACA TTTAGCCCAC AGTTTTATCC 10 CATGAGAAAC CTGAATCTAA TACAAGTTAA ATGACTTGCC TAAGGGCCAC TTGACTAATA GTAATTGAAC CTAAACTTTC AGAATCCAAC TCCAGGAACA TACTTCTAGC ACTATTCATC AATAAAGTTA TATGATAAAT ACATACAACT TTATCTGTCA ACTAAAAATA ACAACAGAGG CTGGGCATGG TGGCTCACAC CCGTAATCCC AGCACTTTGG GAGGCTGAGG CAGGTGGATC ACCTGAGGTC AGGAGTTTGA GACCAGCCTG ACCAACATGG TGAAACCTCA TCTCTACTAA ATATAAAAAA TTAGCTGAGT GTGATAGTGC ATACCTGTAA TCCAGCTACT 15 TAAGAGGCTG AGGCAGGAGG CTTGTTTGAA CCTGGAAGGC AGAGGTTGCA GTGAGCTGAG ATTGTGCCAT TGCACTCCAG CCTGGGCAAT AAGTGCGAAC TCTGTCTCAA AATAATAATA ATAATAATAG AAAATAAAGT TGTCTTCATG AAAAATGAGG AAAGAGATTG CTGGGGTGAG AAACATTAAG ATCAATGGGC ATATGGTGAC CTTCTATGCC CTAGAAACTC TTTTANGGTA TTTTCTCCTG GTATCTCTTT TACNCATCGT TCTATCTGGA AAAATAGGTG GATGAGTGAG ATAATAACGG TATATACTTT TTAAAGGTCT AATTGACATA TATAAATTGC 20 AAGTATTTCA GATGTCAATT TGCTAACCTT GACACACATA GACACACATG AAAACATCAC CACATTAATA CAATGTATGT ATCCATCATT CCAAAAGCTT CCCTGTGTAT CTTTGTAACT CTTTCTTCCT CCCTCCACTC CTTGTCCTCT CGTTCCCAAG AAAACATTGA TCTGCTTCCT GTGAATATAA ATTAACTTAC ATTTTTAGA GCTTTATATA AGTATGTTCT CTTTACTGTT TGTCTTCCTT CGCTGCACAG TTATTTTGAG ATTCTTCAAG TrTTTCTTT ATATCGATAC TTCATTCACA AGAATATATT TTAATTCTAG ACTATGTCAC ATTGACTTTG 25 TCGTCTGCTA AATCCTTAGT GCTCAGATGA CTrGTTCAGG ACTCTCCTTG AACCTGTACC TCTGTTANAT TGAAACTTGT CTCTACTGTC TTTTTATTTC AAACACAGCT TATTAGGTGT CTCTCAACCC ATCAAACNCA CAATCTGAGT CTTTAGGAGA TTGCTTTGAA TTTGTGCTAT TGACTTATAT NTATATNAAA TNTGTAAATG TTTGGTAAAA ATATCATCAT GTACNTTTC ATAATTACGC TATNTNCACA TGATATATGT CAGACTCTGG AAATATGCAT GCCACAGACA CGTGTTTCTT GCCTAAAGGG GCTGATGGAA GACNCACATA CNAATAGACG 30 ATTGCAGTAG AATGAGAGTG GTGGTCTAAN CAGTACATGT CCTGATGTTG CTCGGACAGT TACTACNCCA AGAGTACCCC CTGCATTGTC AGGGTTAGCA TCTCCTGGAA GCCTCATGTA AATGAAGAAT TTCATGCTCC ATCCAGGACC TAATGAATAA GAATCTGCAT TTTAGCAAGA CCCTCATATG ATTCATATAC ACTTTTTTTT TITTTA GATGGAGTCT CACTCTTGTC GCCCAGGCTG GAGTGCAATG GCATGATCTT GGCTCACTGC AACCTCTGCC TCCCGGGTTC AAGTGATTCT CCTGTCTCAG CCTCCCTAGT AGCTGGGACT ACAGGTGCAT 35 GCCACAGTGG CTGGCTAATT TTTGTATTT TAGTAGAGAC AGGGTTTCAC CATTTTGGTC AGGCTGGTCT TGAACTCATG ACCTCCGGTG ATTCCCCCGC CTCGGCTTCC CAAAGTGCTG GGATTACAGA CATGAGCCAC CACACCCGCC TTATTCGTAT ACNCATTTAA TTCTGAGAAG CACTCTATAG AAAATAAGAA TAAGAAAATA TTGGGCTCAC AGGTGACATT AATAAGTAAC TTTATCGAGT ACCCCAAATT TTACCTATGT TTGGAAGATG GGGTTAAAAG GACACATTGA AAACAAGAAC TCATTGTGGC TTTTTTCC TCCTTTTTGA ACAGTTTTCT 40 ATTTCTGGAA TGTTGTCAAT TATATCTGAA AGGAGAAATG CAACATATCT GGTGAGTTGC CCGTTTCTGT CTTTGTCCAT CCTTGAAAAG ATAAGAAGAA CAGAGTTTTA AGAGTCTTAA GGGAAACACA TCTTTGTCTC CTATATTACT TGTGAATGTG GATATATGAT TTTGT7CAA TCTATTTTGT GTCCTAAGGC TTTTTGCAAC AGAAGTTGGA TATATCATTA GAAACATAAA TTGTACCATT TAACATACAT GAAGTTTATG TTTACCTTGA CGTTCTTCTA AAAAGTGTCC TACACCGGCA TTGTCCTTGT AGGCATATTC ACATGATCAA ATAAAATAAT 45 TAGTTTCAA TTAAGGAGAA TATTTGAGGA AAGACCGTAC GTGTTCATGT GGTFCCTGAA GGCAGTCCAG TGAGAAAGTA ATATATGCTT CATTAAACAA TGCGGACATT TTCAGGGTTT CCCTTTTTAA CCAAAATTTG GAAGCAATGT GGAATTTACT GGATGCATCC AGCCCTGAAA TGAAGATAGG TTTATTGAAT GTGCCAGCAA GTGCAGGCCC AGGTCTGAGT GTTCTTCATT ATTATCAGGT GAGAGGAAGC CTGGGAGCAA ACACTGCCAG CAGCATAGCT GGGGGAACGG GAATTACCAT CCTGATCATC AACCTGAAGA AGAGCTTGGC CTATATCCAC 50 ATCCACAGTT GCCAGAAATT TTTTGAGACC AAGTGCTTTA TGGCTTCCTT TTCCACTGTA TGTATTTTTT TTTGTGTGGG AAGACTAAGA TTCTGGGTCC TAATGTAAGT AAGAAGCCCT CTTCTCCTGT TCCATGAACA CCATCCTTTT CTGTAACTTC TATTACACAG TATAGTGGTT CTGTAAGTTC ACACAGCCCA GGGAGATGCT GGCTGCCCAC TCCCCTCAAC CCAGGCAAAT TCCTCGGGGT TAAAGTTATC TACTGCAAGT GACGATCTCT GGGTTTTTCT GTGCCTGTGT TTGTGTGTGT GTGTGTGTGT GTGTGTGTGT GTATGTGTCA CTTTAAAAGG 55 ACTGGTCAGA TGGTAGGGAG ATGAAAACAG GAGATGCTAT AAGAAAATAA ACTTTTGGGG CGAATACCAA TGTGACTCTT TTTGTGTC ATTTGTTGCT GTTCAATAGG AAATTGTAGT GATGATGCTG TTTCTCACCA TTCTGGGACT TGGTAGTGCT GTGTCACTCA CAATCTGTGG AGCTGGGGAA GAACTCAAAG GAAACAAGGT AGATAGAAGC CCGATATAAA ATCTT GAATG ACAGGTTAAC GAATTGGAGC TTTATTCCTT AAAATATGGC CTGGGTTTTC TGAAACATTT CTTCCAGAAA ATAGTTTCTC CAAGTTTTAT TACTTTGGTT TACAAATCTC 60 ACATTTAAAT CACATTTTAT ACCATAAGTA GCACACATTT CATAATATTC CTCTGAATGA GGGTTIGGGAT AATAGGACTG ATATGTTAGA AATGCCTTAA AGTGTGTGGA GCATGAGAGA TGGATGTACA GAAGGCTTGT GAGGAAACCA CCCAGGTATC TGGCCTTGTT TTCTGCCCCA GAACTAGCCG CCTATTCCTG TTTCTGTTTT ATTCCTTTGT TTCTTGACTT TTCCTTTCCA ACTTGCTCTA AAACCTCAGT TTTCTTTCCT TTCTGATTCA TGACTACCAA ATGTTTTCAC TTGCCTCACC CGTCCATTAC ACCTTTGATA AGAACCACCA GACCTTGTGC 65 TCATGTACTT GCCCATGTCT GATGGAAGAA ACATACTCTC TCCATCTGTC CACTTTCCTG AGGCATITCAA GTCTAGCCAC CTTTTAAAAT CACTCTCCTC CAGGCTGGGC ACGGTGTCAC GCCTGTAATC TCAGCACTTT WO 00/62736 PCT/USOO/08020 140 GTGAGGCTGA GGAGGGCGGA TCACTTGAAG TCAGGAGTTC AAAACCAGCC TGGCCAAATG GCAAAACCAA ATC'rrCTTrCA ATTATAACCA AATCTTAAAC CAAATCTCTA CTAAAAAATA CAACAAAACA AAACAACAAC AACAAAAACA GAAAAGGAAA CATTAGCCCA GCGTGGTGGC AGGTACCTGA GGTTCCAGAT ACTTGGGAGG CTGAAGCAGG AGAATCGCTr GAGCCCAAGA GATGGAGGTT GCAGTGAGCC GAGATCATGC CACTGCACCA 5 CAGCCAGGGT GACAGAGCCA TACTTCCCAG CACA'ITGGGA GGCCAAAGCT GAAGAATAAT TTGAGGTGAG GAITI7GGAGA CCAGCCTGGC CAACATGGTG AAACTCCGTC TGTACTAAAA ATATAAAACT TAGTGGGGCA TGGGGGCACA CACCTGTAAT TTCAGCTACT TAGGAGGCTG AGGCAGGAGA ATTGCTTGAA CCCGGGAGGC GGAAG'T1GCA GTGAGCCAAG ATCGTGGCCA CTGCACTCCA GCCTGGGTGA CATAGTGAGA TTCTGTCTCA AAAAAAATAA AAGAAATTTA AAAAATCACT CTCTTCCAAA GATAGATAAA TAAGACAGCA GATATACTAA 10 GGAATAACCT CACCAACTTG TCATTGACTG ACATGATC IIGGCCCA CTTGGCCAGC TAGTCTGGTT TGG'IrCTG GAAATGAAAG AAATAATCAG AGTffAATGA CAGAGAGCGT GAGACCCAGA AAGACAAAAG TAGATGAGGT AAGTCTCTTG AGCGAGACTr CTAGGGATGG GAAA'I=rGTG GTGATTGATA TGAAATGATT TTTCCCTTAT CAGG'ITCCAG AGGATCGTGT TrATGAAGAA YTAAACATAT ATI'CAGCTAC TTACAGTGAG TrFGGAAGACC CAGGGGAAAT GTCTCCTCCC ATTGAYTrAT AAGAATCACG TGTCCAGAAC ACTCTGATrC 15 ACAGCCAAGG ATCCAGAAGG CCAAGGTIT GTrAAGGGGC TACTGGAAAA AnI7CTATTC TCTCCACAGC CTGCTGG'1TT TACATTAGAT TTATrCGCCT GATAAGAATA TTITG ICT GCTGC FrCTG TCCACCTTAA TATGCTCC'I1 CTATI1'GTAG ATATGATAGA CTCCTATT TCTTGnTTA TATI'ATGACC ACACACATCT CTGCTGGAAA GTCAACATGT AGTAAGCAAG A'TrAACTGT TTGATTATAA CTGTGCAAAT ACAGAAAAAA AGAAGGCTGG CTGAAAGTI'G AGTrAAACTT TGACAGTIG ATAATATTTG GT[CTTAGGG TfTTTT 20 TTrAGCAT7 CYFAATAGTT ACAGTTGGGC ATGATTTGTA CCATCCACCC ATACCCACAC AGTCACAGTC ACACACACAT ATGTATTACT TACACTATAT ATAACTTCCT ATGCAAATAT ITrTACCACCA GTCAATAATA CA'T1TGCC AAGACATGAA G=IIATAAA GATCTGTATA ATTGCCTGAA TCACCAGCAC ATTCACTGAC ATGATATTAT 'rrGCAGATTG ACAAGTAGGA AGTGGGGAAC TITATTAAG TTACTCGTTG TCTGGGGAGG TAAATAGG'JT AAAAACAGGG AAATATAAG TGCAGAGATT AACA'ITTCAC AAATG'ITAG TGAAACA'Tr 25 GTGAAAAAAG AAGACTAAAT TAAGACCTGA GCTGAAATAA AGTGACGTGG AAATGGAAAT AATGGTTATA TCTAAAACAT GTAGAAAAAG AGTAACTGGT AGA'II1GT? AACAAA'TFAA AGAATAAAGT TAGACAAGCA ACTGGTTGAC TAATACATTA AGCG'TrGAG TCTAAGATGA AAGGAGAACA CTGGTFTATGT TGATAGAATG ATAAAAAGGG TCGGGCGCGG AGGCTCACGC CTGTAATCCC AGCCCTTTGG GAGGCCGAGG TGGGCAGATC ACGAAGTCAG TAGT-PTGAGA CCAGCCTGGC CAACATAGTG AAACCCCGTC TCTACTAAAA ATACAAAAAA 30 AAAATTAGCT GGGTGTGGTG GCAGTCACCT GJTAGTCCCAG CTACTTGGGA GGATGAGGCA GGAGAATCGC TTrGAACCTGG GAGGCGGAGG TTGCAGTGAG CCGAGATCGC ACCAGTGCAC TCCAGCCTFG GTGACAATGG GAGACTCCAT CTCAAAAAAA AAAAAAAAAA AAAAAAGATA AAAAGTCAGA AATCTGAAAA GTGGAGGAAG AGTACAAATA GACCTAAATT AAGTCTCATT T=GGCTT GATITTrGGGG AGACAAAGGG AAATGCAGCC ATAGAGGGCC TGATGACATC CAATACATGA GTTCTGdTAA AGATAAAATT TGATACACGG 'ITTGGTGTCA 35 'rTATAAGAGA AATCAT]7ATT1 AAATGAAGCA AG'TAACACT CTAAGAGAAT TAYTI'GAGA TAGAAGTGAA GCTAAGCTAA ACTTCACATG CCTATAATTG GAGGGAAAAA CTAAGGATAA AATCTAGCCT AGAAGATACA ATAATI'AGTC ATAAACATGC ATTGTGAAAC TGTAGAGAGC AGGTAGCCCA AAATAGAGAA AGAYTAGATA AAGAGAAAAT AAGTATCCAT CAGAGACAGT ATCTCTAGGC ITGGGCAAGA GAAAAGTCCA CAGTGATAAG CAACTCCACC TAAGGCATGA ATATGCGGCA GAGAAAACAG CAATAGTGAA TGAATGCAAA AGGTGCTGAG 40 CAAATTCCAC ACATGAGTAT TGTGCATGAG TAAATGAATA AAACATrTGC AAAGACCTr AGAGAAAGAG AATGGGAGCA TATGTGCGAA ATAAGATAGT TGATTATGAA TAGAAGGTAG TGAAGAAAAG CAAGCTAAGA AAAAATTCTG '1TTATAAAAG AAGGAAAAGA TAGn7~ATGT 1T=AGCCTA AGTATAAGAG TCCTACAGAT GGACTGAAAA AAATCAGTCT GAGAGTATTA GTCACAATTA ATGAAATAAT TACATITAT GTATTGAGGA TGCCAAGATT AAAAGGTGAC AGGTAGATGT TAAT-CCCT AGATTGTGAA AGTGATCACG ACAATCACAC 45 AACAAATAAT TAAGTGACTT GGTATGC'ITT ATTAATTGT AGGGCCTGAG GT1TTCCA TT CTCA'IT1TC TAAAATACAA TMFGTTTCT CCAAATTI7GA CAGCAGAATA AAAACCCTAC CCTTT7CACTG TGTATCATGC TAAGCTGCAT CTCTACTCTI' GATCATCTGT AGGTATlAAT CACATCAC'JT CCATGGCATG GATGTTCACA TACAGACTCT TAACCCTGGT TTACCAGGAC CTCTAGGAGT GGATCCAATC TATATCTIA CAG'TGTATA GTATATGATA TCTCYITAT TJTCACTCAAT TTATATITC ATCATTGACT ACATATTICT TATACACAAC 50 ACACAA ITTA TGAATITLT CTCAAGATCA YTCTGAGAGT TGCCCCACCC TACCTGCCTT TTATAGTACG CCCACCTCAG GCAGACACAG AGCACAATGC TGGGGTTCTC TTCACACTAT CACTGCCCCA AATTGTCTI17 CTAAA'JCA ACTrCAATGT CATCTI'CTCC ATGAAGACCA CTGAATGAAC ACCTITCAT CCAGCCTI'AA 'TrTCFGCTC CATAACTACT CTATCCCACG ATGCAGTATT GTATCA317AA TTATT1AGTGT GCTTGTGACC TCCTTATGTA TTCTCAAT7A CCTGTA'IMG TGCAATAAAT TGGAATAATG TAAC'ITGATr TCTTATCTGT 55 G'I=GTGTTG GCATGCAAGA TTTAGGTACT TATCAAGATA ATGGGGAATT AAGGCATCAA TAAAATGATG CCAAAGACCA AGAGCAG'ITT CTGAAGTCCT CCTITCATC AGCTCTTrAT CAAACAGAAC ACTCTATAAA CAACCCATAG CCAGAAAACA GGATGTAGGA ACAATCACCA GCACACTCTA TAAACAACCC ATAGCCAGAA AACAGAATGT AAGGACAATC ACCAGCCATC TITGTCAAT AATTGATGGA ATAGAGTI'GA AAGGAACTGG AGCATGAGTC ATATITGACC AGTCAGTCCT CACTCTTL TACTTGCTAT GTAAACTI1GA GAAAGCT'T 60 TTCTCTTTGT GAACCTCAGG TITACATCT GAAAATGAGA AATTrGGAAC AAAAGAYI7CC TAACTGGTCT TTCTGTTCCC ATATTCTGTG ATITCAAT ATTTAGGATT1 TTTGGTAATC ACAAT-rACTT AGT~rGTGGT TGAGATAGCA ACACGAATCA GAACTAYI=7G GTGGACATAT TrTCAAAGGA GTAGCTCTCC ACTITGGGTA AAGAAGTGAT GCNGGTCGTG GTGGCTCACG CCTGTAATCC CAGCACTITA GGGAGGCCAA GGCGGGTGGA TCACGAGGTC AGGAGATCGA GACCATCCTG GCTAACACGG TGAAACCCCG TCTCTACTAA AAAATACAAA 65 AAATTAGCCA GGCGTGGTGG CGGGCGCCTG TAGTCCCACG TACTCGGGAG GCTGAGGCAG GAGAATGGCA TGAACCAGGG AGGCGGAGCT TGCCGTGAGC CGAGATAGCG CCACTGCAGT CCCTCCTGGG CAAAAGAGCA WO 00/62736 PCT/USOO/08020 141 AGACTGCGTC TCAAAAAAAA AAAAAAAAAA AAAAAAAGAA GTGTGTGGAG TAGCAGGACA CCTGCAACAA TAATATTT CTAAATCCCT CTGAAAAATG CTAATCAAAG GGTTTTTC CTAAAAATTG TCTTAGAAAT AAAATCCC CTTTGGGAGA CCGAGGCTGG CAGATCACGA GGTCAGGAGA TAGAGACCAC GGTGAAACCC CGTCTCTACT AAAAATACTA AAAATTAGCC GGGGNGTGGT GGTGGGTACA CCTGTAGTCC CAGCTACTTG 5 GAGGCTGAGG CTGGAGAATC ACGTGAAC-3' (FRAG. NO:_)(SEQ. ID NO:2504) Human Histidine Decarboxylase Nucleic Acid and Antisense Oligonucleotide Fragments 5'-TCT CCC TTG GGC TCT GGC TCC TTC TC TCT CTC TCC CTC TCT CTC TGT CGC CTC CGC CCT GGC TGC TGG GGT GGT GGT GC TTT TGT TCT TCC TTG CTG CC GCC CCG CTG CTT GTC T TC CTC G CTC TGT CCC TCT CTC TCT GTB CTC CTC BGG CTC CBT CBT CTC CCT TGG GC-3'(FRAG. NO:1700) (SEQ. ID NO:1711) 10 5'-GGC TCT GGC (FRAG. NO:1701) (SEQ. ID NO: 1712) 5'-CCC TTG G (FRAG. NO:1702) (SEQ. ID NO: 1713) 5'- TT TGT TCT TCC (FRAG. NO:1703) (SEQ. ID NO: 1714) 5'- TCT CCC TTG GGC TCT GGC TCC TTC TC-3' (FRAG. NO:1024) (SEQ. ID NO: 1034) 5'- TCT CTC TCC CTC TCT CTC TGT -3' (FRAG. NO:1025) (SEQ. ID NO:1035) 15 5'- CGC CTC CGC CCT GGC TGC TGG GGT GGT GGT GC-3' (FRAG. NO:1026) (SEQ. ID NO:1036) 5'- TTT TGT TCT TCC TTG CTG CC-3' (FRAG. NO:1027) (SEQ. ID NO:1037) 5'- GCC CCG CTG CTT GTC T TC CTC G-3' (FRAG. NO:1028) (SEQ. ID NO:1038) 5'-CTC TGT CCC TCT CTC TCT GTB CTC CTC BGG CTC CBT CBT CTC CCT TGG GC (FRAG.NO:1029)(SEQ.ID NO:1039) Human Beta Tryptase Nucleic Acid and Antisense Oligonucleotide Fragments 20 5'-CTT GCT CCT GGG GGC CTC CTG GTC CCT CCG GGT GTT CCC GGC GGG CCT GGC CTG GGG CBG GGG CCG CGT BGG CGC GGC TCG CCB GGB CGG GCB GCG CCB GCB GCB GCB GBT TCB GCB TCC TGG-3' (FRAG. NO:1704) (SEQ. ID NO: 1715) 5'- GCT CCT GGG GGC CT-3' (FRAG. NO:1705) (SEQ. ID NO: 1716) 5'-CGT BGG CGC-3' (FRAG. NO:1706) (SEQ. ID NO: 1717) 25 5'-T GGC CTG GGG-3' (FRAG. NO:1707) (SEQ. ID NO: 1718) 5'-CTT GCT CCT GGG GGC CTC CTG-3' (FRAG. NO:1030) (SEQ. ID NO:1040) 5'-GTC CCT CCG GGT GTT CCC GGC-3' (FRAG. NO:1031) (SEQ. ID NO:1041) 5'-GGG CCT GGC CTG GGG CBG GGG CCG CGT BGG CGC GGC TCG CCB GGB CGG GCB GCG CCB GCB GCB GCB GBT TCB GCB TCC TGG-3' (FRAG. NO:1032) (SEQ. ID NO:1042) 30 Human Tryptase-I Nucleic Acid and Antisense Oligonucleotide Fragments 5'-CTT GCT CCT GGG GGC CTC CTG GTC CCT CTG GCT G TT CCC GGC CCT GGB CTG GGG CBG GGG CCG CGT BGG CGC GGC TCG CCB GGB CGG GCB GCG CCB GCB GCB GCB GGC TCB GCB TCC TGG CCB CGG BBT TCC-3' (FRAG. NO: 1708) (SEQ. ID NO:1719) 5'-CT CCT GGG GGC CTC CTG-3' (FRAG. NO:1709) (SEQ. ID NO:1720) 35 5'-B TCC TGG CCB CGG BBT TCC -3' (FRAG. NO:1710) (SEQ. ID NO:1721) 5'-GTC CCT C-3' (FRAG. NO:1711) (SEQ. ID NO:1722) 5'-CTU GCT CCT GGG GGC CTC CTG-3' (FRAG. NO:1033) (SEQ. ID NO:1043) 5'-GTC CCT CTG GCT G TT CCC GGC-3' (FRAG. NO:1034) (SEQ. ID NO:1044) 5'-CCT GGB CTG GGG CBG GGG CCG CGT BGG CGC GGC TCG CCB GGB CGG GCB GCG CCB GCB GCB GCB 40 GGC TCB GCB TCC TGG CCB CGG BBT TCC -3' (FRAG. NO:1035) (SEQ. ID NO:1045) Human Prostaglandin D Synthase Nucleic Acid and Antisense Oligonucleotide Fragments 5'-GGT GTG CGG GGC CTG GTG CC CCT GGG CCT CGG GTG CTG CCT GT GCG CTG CCT TCT TCT CCT GG GTC CTC GCC GGG GCC CTT GCT GCC CTG GCT GT GCC CTG GGG GTC TGG GTT CGG CTG T CCC CBG CBG GBC CBG TCC CBT CCB CBG CGT GTG BTG BGT BGC CBT TCT CCT GCB GCC GBG-3'(FRAG.NO:1712)(SEQ.ID 45 NO:1723) 5'-T TCT CCT GCB GCC GBG -3' (FRAG. NO:1713) (SEQ. ID NO:1724) 5'-CTT GCT GCC CTG GCT GT-3' (FRAG. NO:1714) (SEQ. ID NO:1725) 5'- TCT TCT CCT GG-3' (FRAG. NO:1715) (SEQ. ID NO:1726) 5'-GGT GTG CGG GGC CTG GTG CC-3' (FRAG. NO:1036) (SEQ. ID NO:1046) 50 5'-CCT GGG CCT CGG GTG CTG CCT GT-3' (FRAG. NO:1037) (SEQ. ID NO:1047) 5'-GCG CTG CCT TCT TCT CCT GG-3' (FRAG. NO:1038) (SEQ. ID NO:1048) 5'-GTC CTC GCC GGG GCC CT GCT GCC CTG GCT GT-3' (FRAG. NO:1039) (SEQ. ID NO:1049) 5'-GCC CTG GGG GTC TGG GTT CGG CTG T-3' (FRAG. NO:1040) (SEQ. ID NO:1050) 5'-CCC CBG CBG GBC CBG TCC CBT CCB CBG CGT GTG BTG BGT BGC CBT TCT CCT GCB GCC GBG -3' 55 (FRAG. NO:1041) (SEQ. ID NO:1051) Human Cyclooxygenase-2 Nucleic Acid and Antisense Oligonucleotide Fragments 5'-GGG CGC GGG CGB GCB TCG C TTT GGG CTT TTC TCC TTT GGT T TGB GCG CCB GGB CCG CGC BCB GCB GCB GGG CGC GGG CGB GCB TCG CBG CGG CGG GCB GGG-3' (FRAG. NO: 1716) (SEQ. ID NO:1729) 5'-G GCB GGG -3' (FRAG. NO: 1717) (SEQ. ID NO: 1730) 60 5'-TCC TTT GGT T-3' (FRAG. NO:1718) (SEQ. ID NO:1731) 5'- GGG CGC GGG CGB GCB TCG C-3' (FRAG. NO:1042) (SEQ. ID NO:1052) 5'- TTT GGG CTT TTC TCC TTT GGT T-3' (FRAG. NO:1043) (SEQ. ID NO:1053) 5'-TGB GCG CCB GGB CCG CGC BCB GCB GCB GGG CGC GGG CGB GCB TCG CBG CGG CGG GCB GGG -3' WO 00/62736 PCT/USOO/08020 142 (FRAG. NO:1044) (SEQ. ID NO:1054) Human Eosinophil Cationic Protein Nucleic Acid and Antisense Oligonucleotide Fragments 5'-CCT CCT TCC TGG TCT GTC TGC CBG BCB BBT TTG GGB BGT GBB CBG TTT TGG BBC CBT GTT TCC CBG TCT CTG BGC TGT GGC-3' (FRAG. NO: 1719) (SEQ. ID NO: 1732) 5 5'-TTC TCC TTT GGT T-3' (FRAG. NO:1720) (SEQ. ID NO: 1733) 5'-T TTC TCC TTT GGT T-3' (FRAG. NO:1721) (SEQ. ID NO:1734) 5'- GGG CGC GGG CGB GCB TCG C-3' (FRAG. NO:1042) (SEQ. ID NO:1052) 5'- TTT GGG CTT C TCC TTT GGT T-3' (FRAG. NO:1043) (SEQ. ID NO:1053) 5'-TGB GCG CCB GGB CCG CGC BCB GCB GCB GGG CGC GGG CGB GCB TCG CBG CGG CGG GCB GGG -3' 10 (FRAG. NO:1044) (SEQ. ID NO:1054) Human Eosinophil Derived Neurotoxin Nucleic Acid and Antisense Oligonucleotide Fragments 5'-GCC CTG CTG CTC TTT CTG CT TCC CTT GGT GGG TTG GGC C GCT GGT TGT TCT GGG GTT C TTG CTG CCC CTT CTG TCC C TGT TTG CTG GTG TCT GCG C 5'- CCC CBB CBG BBG BBG CBG BCB BBT TTG GGB BGT GBB CBG TT7 TGG BBC CBT GTT TCC TGT-3' (FRAG. NO: 1722) (SEQ. ID NO: 1735) 15 5'-TTC CTG T-3' (FRAG. NO:1723) (SEQ. ID NO: 1736) 5'-CTC TTT CTG CT-3' (FRAG. NO: 1724) (SEQ. ID NO:1737) 5'-CCC CTT CTG TCC C-3' (FRAG. NO:1725) (SEQ. ID NO: 1738) 5'- GCC CTG CTG CTC TTT CTG CT-3' (FRAG. NO:1047) (SEQ. ID NO:1055) 5'- TCC CTT GGT GGG TTG GGC C-3' (FRAG. NO:1048) (SEQ. ID NO:1056) 20 5'- GCT GGT TGT TCT GGG GTT C-3' (FRAG. NO:1049) (SEQ. ID NO:1058) 5'- TTG CTG CCC CTT CTG TCC C-3' (FRAG. NO:1050) (SEQ. ID NO:1057) 5'- TGT TTG CTG GTG TCT GCG C -3' FRAGG. NO:1051) (SEQ. ID NO:1059) 5'- CCC CBB CBG BBG BBG CBG BCB BBT TG GGB BGT GBB CBG TTT TGG BBC CBT GTT TCC TGT-3' (FRAG. NO:1052) (SEQ. ID NO:1060) 25 Human Eosinophil Peroxidase Nucleic Acid and Antisense Oligonucleotide Fragments 5'-GCG CTC GGC CTG GTC CCG G GGG TCT CCT CTT GTT GTT GC TTG CGC CTC CTG CTG GGG GT CC CTC TGT TCT TGT TT7 GGG GGC GGG CCC GGC CGT TGT CTT GTT TGG GGG TTT CCG TTG GGG TTC TCC TGG CCC GGG CCT TGC CC GGC CGT GGT CCC GGC TTC GTTCCT GTC TCC GTC TCG GCT CTT CTG GGG CCT TGC GCT GTC TTT GGT G 5'-GCB CCG TCC BGT GBT GGT GCG GTB CTU GTC GCT GCB GCG CTC GGC 30 CTG GTC CCG GBG BGC CACCGCTCCT GTCAGCCAAC AAATATCCAT TGAGCGACAC CTGTGTCCCA GGTGCTGCTC TGGGCCCTGG GAGAAGTGCA TCAGTGGGCT TGGTAGTAGA GGGTAGGGAT GGAGTGAAGG GTAGGCAGGA AGAATGTCCC CAGGCTGGTA GGAGGTGGGG TGGGGGGTTT CAGTCTCAAA ACTCCCATGA AAACCAGAGA GAAGTTTCAG AACTCCACCC AAGAGGCTGG GTTTCTAGGG CCCAGAGCTG CCCTCCCCCA CCCTAGAATG GGCTATAAAA GTCCCTTCCC AGCTACGTCC AGAGAAGAGC TGGAGGAAGT GAGAGGTCGG 35 CTGGGGGTCC TCAAAGTGAG AGGGGAGCAG AGGATCCTCC CGTGCAGGCT GTGGATGTCA CTCACTTCCC AGCTGGTGAA GCCTCGCTGC AGAGATGCAT CTGCTCCCAG CCCTGGCAGG GGTCCTGGCC ACACTCGTCC TCGCCCAGCC CTGTGAGGGC ACTGACCCAG GTAATAGTCC CCTAGACAGG CAAGGAGGAG GGAGGGGAAA TGGAAGGGGA AGCACTTGGG TCTTGGAGGG GGTCTTGTGG CTTGCTGAAC CCTGAGTCCC CATCTCTTTG AACAGCCTCC CCTGGGGCAG TGGAGACCTC GGTCCTGCGA GACTGCATAG CAGAGGCCAA GTTGCTGGTG 40 GATGCTGCCT ACAATTGGAC CCAGAAGAGG TGGACTTGGG TCTGGGGGCT GCATGGGCCT GGGAGGATCA GT TAATACCTTG TGGGGTCAGG GAGCCCATGT CCCGTGCTGA TGTTATrTCC CCACCAGGTC CGGGCTGTCT CCAACCAGAT TGTGCGCTTC CCCAATGAGA GACTGACCTC CGACCGTGGC CGAGCCCTCA TGTTCATGCA GTGGGGCCAG TTCATTGACC ATGACCTGGA CTTCTCCCCG GAGTCCCCGG CCAGAGTGGC CTTCACTGCA GGCGTT1GACT GTGAGAGGAC CTGCGCCCAG CTGCCCCCCT GCTTTCCCAT CAAGGTACCT ACCCTCAGCC 45 AATCTCCCAT GCCCTTGTGT GGCCTCCCCC AAAGGCAAGG TGCTGGGGGT GGGGATCTGG AAGACTGGAG CACCATCCTT AAGGAGCTGC CTGTGGAGCT AGGGTATGAG ACAGAGACAC AAG CACTGTCTCC TCTTCCATCT CAGATCCCAC CCAATGACCC CCGCATCAAG AACCAGCGTG ACTGCATCCC TTTCTTCCGC TCGGCACCCT CATGCCCCCA AAACAAGAAC AGAGTCCGCA ACCAGATCAA CGCGCTCACC TCCTTTGTGG ACGCCAGCAT GGTGTATGGC AGTGAGGTCT CCCTCTCGCT GCGGCTCCGC AACCGGACCA ACTACCTGGG 50 GCTGCTGGCC ATCAACCAGC GCT'17CAAGA CAACGGCCGG GCCCTGCTGC CCTTCGACAA CCTGCACGAT GACCCCTGTC TCCTCACCAA CCGCTCGGCG CGCATCCCCT GCTTCCTGGC AGGTCAGACA GGGAGGAAGG TGGTGTCTTC CCAGGAAACA GCCATCCCTG GGGTCCCAAC TGGGAAGCAA TGGTGGGATG TGGTGAAGGT ACATGGTTTG GGACCTCAGT ATTAGGCACA CCATAAGCAT GGATCTGTGC AC TGAAGAGATG GAGGTCCAGT GAGGGCCAGG AGTTTGGCCC ACCCCGTCTC TCCCATCCCC AGCCCTGGGT CTACCCTGGT 55 AGAAAGACAT TTCTCTGGGA AAGGCTGCAG TAAATCTGAG CTTGGGGTTT TCAAGGTGAC ACCCGATCAA CGGAAACCCC CAAACTGGCA GCCATGCACA CCCTCTTTAT GCGAGAGCAC AACCGGCTGG CCACCGAGCT GAGACGCCTG AATCCCCGGT GGAATGGAGA CAAACTGTAC AATGAGGCTC GGAAGATCAT GGGGGCCATG GTCCAGGTAA GGAGCTCTGC ATCCCAGCAT CCCCC CTTTGTATCT CCACCCACCA ATAGTAAATT AATGTTGTCA CATTTGACGT GATGACAATA AAGAATATGT CTGAGCCACC CTTTGAAAAG GCAAGGGTAT 60 GGGTGAGTAG CCTCTGGGGA ATGTTCCTCC TGTCTCCCT TCCAGATCAT CACCTACCGA GACTTTCTGC CCCTGGTTCT GGGCAAGGCC CGGGCCAGGA GAACCCTGGG GCACTACAGG GGGTACTGCT CCAATGTGGA CCCACGGGTG GCCAATGTCT TCACCCTGGC CTTCCGCTTT GGCCACACAA TGCTCCAGCC CTTCATGTTC CGCTTGGACA GTCAGTACCG GGCCTCCGCA CCCAACTCGC ATGTCCCACT TAGCTCTGCC TTCTTTGCCA GCTGGCGGAT CGTGTATGAA GGTGACCAGG TTTTCCAGGG GGCAAATGGG GGTGAGGGTG GGGAGCATGC 65 CCTCCCCTAG GTGG TCCAGCTGCT TCATGTCTCT CCAGAACTCT GTTTCCTGAC AAACGTTACT WO 00/62736 PCT/USOO/08020 143 AACATACCCG ACTGGCTTGT CCAGCTCTGG GCTAGCTTGG CATCATGTGA TAACCCAAGT AGCTTCCCAG AGGCTGGTCC AATCTGTGCT GCTCACATTC CCTGCCACCA GGGGGCATCG ACCCCATCCT CCGGGGCCTC ATGGCCACCC CTGCCAAGCT GAACCGTCAG GATGCCATGT TAGTGGATGA GCTCCGGGAC CGGCTGTTTC GGCAAGTGAG GAGGATTGGG CTGGACCTGG CAGCTCTCAA CATGCAACGA AGCCGGGACC ACGGCCTrCC 5 AGGTGAGGGG GCTGTCCACC TCTTCTCCCA GCTTGCTCG GGCCAGGCTG CTCAAGGGGT TCTGGGAAGA CCCTGGTACC CGACTGCCTG GTAGGTTCTG GTGGCAGAAA CGAGGTGTTT TCACCAAAAG ACAGCGCAAG GCCCTGAGCA GAATTTCCTT GTCTCGAATT ATATGTGACA ATACCGGTAT CACCACGGTT TCAAGGGACA TCTTCAGAGC CAACATCTAC CCTCGGGGCT TTGTGAACTG CAGCCGTATC CCCAGGTTGA ACCTATCAGC CTGGCGAGGG ACATGAGGCT TCTGCAGGTA AGGGGAGGCC ACCTCCAGCA CCCTGGGCTG GTTAAGCCTC 10 ACATCCTTCC CTGGATGGAT GGCTGAGTCC TCTTAGGTCT CTAAGCAGAG AAAACAGAAC TTGTCACTAG GTACTCTTTC CAAGTGGCTT CCCAATGTGC TAGTTCTGG GCTGACAGTC AATTCCAGGC CCTAGGACTT TGGGGGGAAA TTAGGAGCAT CCAACTA GAATTCCGTG GCCAGGACCC CTGCCAGGGC ACTGACCCAG CCTCCCCTGG GGCAGTGGAG ACCTCGGTCC TGCGAGACTG CATAGCAGAG GCCAAGTTGC TGGTGGATGC TGCCTACAAT TGGACCCAGA AGAGCATCAA GCAGCGGC'TT CGCAGCGGTT CAGCCAGCCC CATGGACCTC 15 CTGTCCTACT TCAAACAACC GGTAGCAGCC ACCAGGACAG TTGTTCGGGC CGCAGATTAT ATGCATGTGG CTTTGGGGCT GCTTGAAGAG AAGTTACAAC CCCAGCGGTC CGGACCCTIC ATTGTCACTG ATGTGCTAAC AGAACCACAG CTGCGGCTGC TGTCCCAGGC CAGTGGCTGT GCTCTCCGGG ACCAGGCCGA GCGCTGCAGC GACAAGTACC GCACCATCAC TGGACGGTGC AACAACAAGA GGAGACCCTT GCTAGGGGCC TCCAACCAGG CTCTGGCTCG CTGGCTGCCC GCCGAGTATG AGGATGGGCT GTCGCTCCCC TTCGGCTGGA CCCCCAGCAG 20 GAGGCGCAAT GGCTTCCTTC TCCCTCTTGT CCGGGCTGTC TCCAACCAGA TTGTGCGCTT CCCCAATGAG AGACTGACCT CCGACCGTGG CCGAGCCCTC ATGTTCATGC AGTGGGGCCA GTTCATTGAC CATGACCTGG ACTTCTCCCC GGAGTCCCCG GCCAGAGTGG CCTTCACTGC AGGCGTTGAC TGTGAGAGGA CCTGCGCCCA GCTGCCCCCC TGCTTTCCCA TCAAGATCCC ACCCAATGAC CCCCGCATCA AGAACCAGCG TGACTGCATC CCTTTCTFCC GCTCGGCACC CTCATGCCCC CAAAACAAGA ACAGAGTCCG CAACCAGATC AACGCGCTCA 25 CCTCCTTGT GGACGCCAGC ATGGTGTATG GCAGTGAGGT CTCCCTCTCG CTGCGGCTCC GCAACCGGAC CAACTACCTG GGGCTGCTGG CCATCAACCA GCGCTTTCAA GACAACGGCC GGGCCCTGCT GCCCTTCGAC AACCTGCACG ATGACCCCTG TCTCCTCACC AACCGCTCGG CGCGCATCCC CTGCTTCCTG GCAGGTGACA CCCGATCAAC GGAAACCCCC AAACTGGCAG CCATGCACAC CCTCTTTATG CGAGAGCACA ACCGGCTGGC CACCGAGCTG AGACGCCTGA ATCCCCGGTG GAATGGAGAC AAACTGTACA ATGAGGCTCG GAAGATCATG 30 GGGGCCATGG TCCAGATCAT CACCTACCGA GACTTTCTGC CCCTGGTTCT GGGCAAGGCC CGGGCCAGGA GAACCCTGGG GCACTACAGG GGGTACTGCT CCAATGTGGA CCCACGGGTG GCCAATGTCT TCACCCTGGC CTTCCGCTT GGCCACACAA TGCTCCAGCC CTTCATGTTC CGCTTGGACA GTCAGTACCG GGCCTCCGCA CCCAACTCGC ATGTCCCACT TAGCTCTGCC TTCTTTGCCA GCTGGCGGAT CGTGTATGAA GGGGGCATCG ACCCCATCCT CCGGGGCCTC ATGGCCACCC CTGCCAAGCT GAACCGTCAG GATGCCATGT TAGTGGATGA 35 GCTCCGGGAC CGGCTGTTTC GGCAAGTGAG GAGGATTGGG CTGGACCTGG CAGCTCTCAA CATGCAACGA AGCCGGGACC ACGGCCTTCC AGGGTACAAT GCTrGGAGGC GCTTCTGTGG GCTCTCCCAG CCCCGGAATT TGGCACAGCT TAGCCGGGTG CTGAAAAACC AGGACTTGGC AAGGAAGTTC CTGAATTTGT ATGGAACACC TGACAACATT GACATCTGGA TTGGGGCCAT CGCTGAGCCT CrTGCCGG GGGCTCGAGT GGGGCCTCTT CTGGCTTGTC TGTTCGAGAA CCAGTTCAGA AGAGCCGAGA CGGAGACAGG ITTCTGGTGGC AGAACGAGGT 40 GTTTTCACCA AAGACAGCGC AAGGCCCTGA GCAGAATTTC CTTGTCTCGA ATTATATGTG ACAATACCGG TATCACCACG GTTTCAAGGG ACATCTTCAG AGCCAACATC TACCCTCGGG GCTTTGTGAA CTGCAGCCGT ATCCCCAGGT TGAACCTATC AGCCTGGCGA GGGACATGAG GCTTCTGCAG GAGTCTATCC CAAGTCTCCA ACTTTrGGAG ACAAGGGGAA GGGGAGGACC ATGAGGCTGC CTTGTCTCCC TGGAGCAAGT GCAGGCTCGT GACGCTTCTG CTGGCTACAG CTCAGAGCTG GGTTCCCCAG CCAGGAGTGA AGGCTGGGGG CTCCTATCAG 45 CAATGGACCT TCCGCCTTGG GAGCCTCTTA GGTATTAGGC TATGAATCAG CGCCACGTGC AAAGGCTTGG GAGCCAAGCC ATGTGGTCTT GCACCCCAGG CAAGAAAAGT CAGCTGGAGG GTTTACAGCA CTTFCTACTG TTTCCCAGCC CTCCCTCCCC TCCCTCACCA TGACTAAGAG ACCACTCGGT CCTAGCCTCC AGACACCCCA CAATACTCCT CTGAGCCTGA GGCCAGGCAG CATGCTCTGC TTCTACCAAT AAAGCACTGC CGGAATTC-3' (FRAG. NO: 1726) (SEQ. ID NO: 3008) 50 5'-CACCGCTCCT GTCAGCCAAC AAATATCCAT TGAGCGACAC CTGTGTCCCA GGTGCTGCTC TGGGCCCTGG GAGAAGTGCA TCAGTGGGCT TGGTAGTAGA GGGTAGGGAT GGAGTGAAGG GTAGGCAGGA AGAATGTCCC CAGGCTGGTA GGAGGTGGGG TGGGGGGTTT CAGTCTCAAA ACTCCCATGA AAACCAGAGA GAAGTTTCAG AACTCCACCC AAGAGGCTGG GTTTCTAGGG CCCAGAGCTG CCCTCCCCCA CCCTAGAATG GGCTATAAAA GTCCCTTCCC AGCTACGTCC AGAGAAGAGC TGGAGGAAGT GAGAGGTCGG CTGGGGGTCC TCAAAGTGAG 55 AGGGGAGCAG AGGATCCTCC CGTGCAGGCT GTGGATGTCA CTCACT7CCC AGCTGGTGAA GCCTCGCTGC AGAGATGCAT CTGCTCCCAG CCCTGGCAGG GGTCCTGGCC ACACTCGTCC TCGCCCAGCC CTGTGAGGGC ACTGACCCAG GTAATAGTCC CCTAGACAGG CAAGGAGGAG GGAGGGGAAA TGGAAGGGGA AGCACTTGGG TCTTGGAGGG GGTCTTGTGG CTTGCTGAAC CCTGAGTCCC CATCTCTTTG AACAGCCTCC CCTGGGGCAG TGGAGACCTC GGTCCTGCGA GACTGCATAG CAGAGGCCAA GTTGCTGGTG GATGCTGCCT ACAATTGGAC 60 CCAGAAGAGG TGGACTTGGG TCTGGGGGCT GCATGGGCCT GGGAGGATCA GT-3' (FRAG. NO:_)(SEQ. ID NO:2483) 5'-TAATACCTTG TGGGGTCAGG GAGCCCATGT CCCGTGCTGA TGTTATTTCC CCACCAGGTC CGGGCTGTCT CCAACCAGAT TGTGCGCTTC CCCAATGAGA GACTGACCTC CGACCGTGGC CGAGCCCTCA TGTTCATGCA GTGGGGCCAG TTCATTGACC ATGACCTGGA CTTCTCCCCG GAGTCCCCGG CCAGAGTGGC CTTCACTGCA 65 GGCGTTGACT GTGAGAGGAC CTGCGCCCAG CTGCCCCCCT GCITTCCCAT CAAGGTACCT ACCCTCAGCC AATCTCCCAT GCCCTTGTGT GGCCTCCCCC AAAGGCAAGG TGCTGGGGGT GGGGATCTGG AAGACTGGAG WO 00/62736 PCT/USOO/08020 144 CACCATCCYIT AAGGAGCTGC CTGTGGAGCT AGGGTATGAG ACAGAGACAC AAG-3' (FRAG.NQ:_)(SEQ.ID NO:2484) 5'-CACTGTCTCC TCTTCCATCT CAGATCCCAC CCAATGACCC CCGCATCAAG AACCAGCGTG ACTGCATCCC TfrC= CCGC TCGGCACCCT CATGCCCCCA AAACAAGAAC AGAGTCCGCA ACCAGATCAA CGCGCTCACC 5 TCCTTGTGG ACGCCAGCAT GGTGTATGGC AGTGAGGTCT CCCTCTCGCT GCGGCTCCGC AACCGGACCA ACTACCTGGG GCTGCTGGCC ATCAACCAGC GCTrCAAGA CAACGGCCGG GCCCTGCTGC CCTTCGACAA CCTGCACGAT GACCCCTGTC TCCTCACCAA CCGCTCGGCG CGCATCCCCT GCTTCCTGGC AGGTCAGACA GGGAGGAAGG TGGTGTCTTC CCAGGAAACA GCCATCCCTG GGGTCCCAAC TGGGAAGCAA TGGTGGGATG TGGTGAAGGT ACATGGTTTG GGACCTCAGT ATT1AGGCACA CCATAAGCAT GGATCTGTGC AC-3' 10 (FRAG.NO:_)(SEQ.ID NO:2485) 5'-TGAAGAGATG GAGGTCCAGT GAGGGCCAGG AG'TrGGCCC ACCCCGTCTC TCCCATCCCC AGCCCTGGGT CTACCCTGGT AGAAAGACAT TTCTCTGGGA AAGGCTGCAG TAAATCTGAG CYTGGGGTTT TCAAGGTGAC ACCCGATCAA CGGAAACCCC CAAACTGGCA GCCATGCACA CCCTC'ITTAT GCGAGAGCAC AACCGGCTGG CCACCGAGCT GAGACGCCTG AATCCCCGGT GGAATGGAGA CAAACTGTAC AATGAGGCTC GGAAGATCAT 15 GGGGGCCATG GTCCAGGTAA GGAGCTCTGC ATCCCAGCAT CCCCC-3' (FRAG.NO:_)(SEQ.IDNO:2486) 5'-C'rGTATCT CCACCCACCA ATAGTAAAT7 AATGTrGTCA CA'TrGACGT GATGACAATA AAGAATATGT CTGAGCCACC CTfTGAAAAG GCAAGGGTAT GGGTGAGTAG CCTCTGGGGA ATG'I1CCTCC TGTCTTCCCT TCCAGATCAT CACCTACCGA GACT1CTGC CCCTGGTrCT GGGCAAGGCC CGGGCCAGGA GAACCCTGGG GCACTACAGG GGGTACTGCT CCAATGTGGA CCCACGGGTG GCCAATGTCT TCACCCTGGC CTIFCCGCT1T 20 GGCCACACAA TGCTCCAGCC CTT1CATGTTC CGCTTGGACA GTCAGTACCG GGCCTCCGCA CCCAACTCGC ATGTCCCACT TAGCTCTGCC TTCTTTGCCA GCTGGCGGAT CGTGTATGAA GGTGACCAGG TITTCCAGGG GGCAAATGGG GGTGAGGGTG GGGAGCATGC CCTCCCCTAG GTGG-3' (FRAG.NO:_)(SEQ.ID NO:2487) 5'-TCCAGCTGCT TCATGTCTCT CCAGAACTCT GTrTCCTGAC AAACGTTACT AACATACCCG ACTGGCTTGT CCAGCTCTGG GCTAGCTTGG CATCATGTGA TAACCCAAGT AGCTTCCCAG AGGCTGGTCC AATCTGTGCT 25 GCTCACATTC CCTGCCACCA GGGGGCATCG ACCCCATCCT CCGGGGCCTC ATGGCCACCC CTGCCAAGCT GAACCGTCAG GATGCCATGT TAGTGGATGA GCTCCGGGAC CGGCTGMr'C GGCAAGTGAG GAGGA'I1GGG CTGGACCTGG CAGCTCTCAA CATGCAACGA AGCCGGGACC ACGGCCTTCC AGGTGAGGGG GCTGTCCACC TCTTCTCCCA GCTPGCTCG GGCCAGGCTG CTCAAGGGGT TCTGGGAAGA CCCTGGTACC-3' (FRAG.NO:_)(SEQ.ID NO:2488) 30 5'-CGACTGCCTG GTAGGTTCTG GTGGCAGAAA CGAGGTG'IM TCACCAAAAG ACAGCGCAAG GCCCTGAGCA GAATI'TCC'r GTCTCGAATT ATATGTGACA ATACCGGTAT CACCACGGTT TCAAGGGACA TCTTCAGAGC CAACATCTAC CCTCGGGGCT TrGTGAACTG CAGCCGTATC CCCAGGTTGA ACCTATCAGC CTGGCGAGGG ACATGAGGCT TCTGCAGGTA AGGGGAGGCC ACCTCCAGCA CCCTGGGCTG GTTAAGCCTC ACATCCTTCC CTGGATGGAT GGCTGAGTCC TC'ITAGGTCT CTAAGCAGAG AAAACAGAAC Tr1GTCACTAG GTACTCTTTC 35 CAAGTGGCTT CCCAATGTGC TAGTI1TCTGG GCTGACAGTC AATrCCAGGC CCTAGGACTT TGGGGGGAAA TI'AGGAGCAT CCAACTA-3' (FRAG.NO:_)(SEQ.ID NO:2489) 5'-GAATTCCGTG GCCAGGACCC CTGCCAGGGC ACTGACCCAG CCTCCCCTGG GGCAGTGGAG ACCTCGGTCC TGCGAGACTG CATAGCAGAG GCCAAGTT1GC TGGTGGATGC TGCCTACAAT TGGACCCAGA AGAGCATCAA GCAGCGGCTTr CGCAGCGGTT~ CAGCCAGCCC CATGGACCTC CTGTCCTACT TCAAACAACC GGTAGCAGCC 40 ACCAGGACAG TTGT-rCGGGC CGCAGAITAT ATGCATGTGG CTI7GGGGCT GCrrGAAGAG AAGTTACAAC CCCAGCGGTC CGGACCCTTC ATTGTCACTG ATGTGCTAAC AGAACCACAG CTGCGGCTGC TGTCCCAGGC CAGTGGCTGT GCTCTCCGGG ACCAGGCCGA GCGCTGCAGC GACAAGTACC GCACCATCAC TGGACGGTGC AACAACAAGA GGAGACCCT-r GCTAGGGGCC TCCAACCAGG CTCTGGCTCG CTGGCTGCCC GCCGAGTATG AGGATGGGCT GTCGCTCCCC TTCGGCTGGA CCCCCAGCAG GAGGCGCAAT GGCTT1CCTI7C TCCCTCTTGT 45 CCGGGCTGTC TCCAACCAGA TTGTGCGCTT CCCCAATGAG AGACTGACCT CCGACCGTGG CCGAGCCCTC ATGTTrCATGC AGTGGGGCCA GTTCATrGAC CATGACCTGG ACTTCTCCCC GGAGTCCCCG GCCAGAGTGG CCTTCACTGC AGGCGTTGAC TGTGAGAGGA CCTGCGCCCA GCTGCCCCCC TGC'TrTCCCA TCAAGATCCC ACCCAATGAC CCCCGCATCA AGAACCAGCG TGACTGCATC CCTTTCTTCC GCTCGGCACC CTCATGCCCC CAAAACAAGA ACAGAGTCCG CAACCAGATC AACGCGCTCA CCTCCTTGT GGACGCCAGC ATGGTGTATG 50 GCAGTGAGGT CTCCCTCTCG CTGCGGCTCC GCAACCGGAC CAACTACCTG GGGCTGCTGG CCATCAACCA GCGC'ITTCAA GACAACGGCC GGGCCCTGCT GCCCTTCGAC AACCTGCACG ATGACCCCTG TCTCCTCACC AACCGCTCGG CGCGCATCCC CTGCTTCCTG GCAGGTGACA CCCGATCAAC GGAAACCCCC AAACTGGCAG CCATGCACAC CCTCTTrATG CGAGAGCACA ACCGGCTGGC CACCGAGCTG AGACGCCTGA ATCCCCGGTG GAATGGAGAC AAACTGTACA ATGAGGCTCG GAAGATCATG GGGGCCATGG TCCAGATCAT CACCTACCGA 55 GAC'TTrCTGC CCCTGGTTCT GGGCAAGGCC CGGGCCAGGA GAACCCTGGG GCACTACAGG GGGTACTGCT CCAATGTGGA CCCACGGGTG GCCAATGTCT TCACCCTGGC CTTCCGCMf GGCCACACAA TGCTCCAGCC C TCATGTTC CGCTTGGACA GTCAGTACCG GGCCTCCGCA CCCAACTCGC ATGTCCCACT TAGCTCTGCC TT'TGCCA GCTGGCGGAT CGTGTATGAA GGGGGCATCG ACCCCATCCT CCGGGGCCTC ATGGCCACCC CTGCCAAGCT GAACCGTCAG GATGCCATGT TAGTGGATGA GCTCCGGGAC CGGCTGTTTC GGCAAGTGAG 60 GAGGAVI7GGG CTGGACCTGG CAGCTCTCAA CATGCAACGA AGCCGGGACC ACGGCCL1CC AGGGTACAAT GCTTGGAGGC GCTTCTGTGG GCTCTCCCAG CCCCGGAA Fr TGGCACAGCT TAGCCGGGTG CTGAAAAACC AGGACTTGGC AAGGAAGTT1C CTGAAThrGT ATGGAACACC TGACAACATT GACATCTGGA T-FGGGGCCAT CGCTGAGCCT CTTTGCCGG GGGCTCGAGT GGGGCCTC'IT CTGGCTTGTC TGTrTCGAGAA CCAGTITCAGA AGAGCCGAGA CGGAGACAGG TTCTGGTGGC AGAACGAGGT GT=CACCA AAGACAGCGC AAGGCCCTGA 65 GCAGAATTTC c'IrGTC'rCGA ATTATATGTG ACAATACCGG TATCACCACG G'ITTCAAGGG ACATCTTCAG AGCCAACATC TACCCTCGGG GCTTTGTGAA CTGCAGCCGT ATCCCCAGGT TGAACCTATC AGCCTGGCGA WO 00/62736 PCT/USOO/08020 145 GGGACATGAG GCTTCTGCAG GAGTCTATCC CAAGTCTCCA ACTTTTGGAG ACAAGGGGAA GGGGAGGACC ATGAGGCTGC CTTGTCTCCC TGGAGCAAGT GCAGGCTCGT GACGCTTCTG CTGGCTACAG CTCAGAGCTG GGT'rCCCCAG CCAGGAGTGA AGGCTGGGGG CTCCTATCAG CAATGGACCT TCCGCCTTGG GAGCCTCTTA GGTATTAGGC TATGAATCAG CGCCACGTGC AAAGGCTTGG GAGCCAAGCC ATGTGGTCTT GCACCCCAGG 5 CAAGAAAAGT CAGCTGGAGG GTTTACAGCA CTTTCTACTG TTTCCCAGCC CTCCCTCCCC TCCCTCACCA TGACTAAGAG ACCACTCGGT CCTAGCCTCC AGACACCCCA CAATACTCCT CTGAGCCTGA GGCCAGGCAG CATGCTCTGC TTCTACCAAT AAAGCACTGC CGGAATTC-3' (FRAG.NO:_) (SEQ. ID no:2490) 5'-TC GGC CTG GTC CCG G-3' (FRAG. NO: 1727) (SEQ. ID NO:1740) 5'-TGG GGG TTT CCG TTG-3' (FRAG. NO: 1728) (SEQ. ID NO: 1741) 10 5'-TG GTC CCG GBG BGC -3' (FRAG. NO: 1729) (SEQ. ID NO: 1742) 5'-GCG CTC GGC CTG GTC CCG G-3' (FRAG. NO:1053) (SEQ. ID NO:1061) 5'-GGG TCT CCT CTT GTT GTT GC-3' (FRAG. NO:1054) (SEQ. ID NO:1062) 5'- TTG CGC CTC CTG CTG GGG GT CC-3' (FRAG. NO:1055) (SEQ. ID NO:1063) 5'-CTC TGT TCT TGT TTT GGG GGC-3' (FRAG. NO:1056) (SEQ. ID NO:1064) 15 5'-GGG CCC GGC CGT TGT CTT G-3' FRAGG. NO:1057) (SEQ. ID NO:1065) 5'-GTT TGG GGG TT CCG TTG-3' (FRAG. NO:1058) (SEQ. ID NO:1066) 5'-GGG TTC TCC TGG CCC GGG CCT TGC CC-3' (FRAG. NO:1059)(SEQ. ID NO:1067) 5'-GGC CGT GGT CCC GGC TTC GTT GC-3' (FRAG. NO:1060) (SEQ. ID NO:1068) 5'-CCT GTC TCC GTC TCG GCT CTT CTG-3' (FRAG. NO:1061) (SEQ. ID NO:1069) 20 5'-GGG CCT TGC GCT GTC TTT GGT G-3' (FRAG. NO:1062) (SEQ. ID NO:1070) 5'-GCB CCG TCC BGT GBT GGT GCG GTB CTT GTC GCT GCB GCG CTC GGC CTG GTC CCG GBG BGC -3' (FRAG. NO:1063) (SEQ. ID NO:1071) Human Intercellular Adhesion Molecule-1 (ICAM-1) Nucleic Acid and Antisense Oligonucleotide Fragments 25 5'-GCG CGG GCC GGG GGC TGC TGG G GGT TGG CCC GGG GTG CCC C GCC GCT GGG TGC CCT CGT CCT CTG CGG TC GTG TCT CCT GGC TCT GGT TCC CC GCT GCG CCC GTT GTC CTC TGG GGT GGC CTT C GCT CCC GGG TCT GGT TCT TGT GT TGG GGG TCC CTT TTT GGG CCT GTT GT GGC GTG GCT TGT GTG TTC GGT TTC TGC CCT GTC CTC CGG CGT CCC CGG BGC CTC CCC GGG GCB GGB TGB CTT TTG BGG GGG BCB CBG BTG TCT GGG CBT TGC CBG GTC CTG GGB BCB GBG CCC CGB GCB GGB CCB GGB GTG CGG GCB GCG CGG 30 GCC GGG GGC TGC TGG GBG CCB TBG CGB GGC TGB G-3' (FRAG. NO: 1730) (SEQ. ID NO: 1743) 5'-GGG GGC TGC TGG G-3' (FRAG. NO: 1731) (SEQ. ID NO:1744) 5'-T GTC CTC CGG CGT CCC-3' (FRAG. NO:1732) (SEQ. ID NO:1745) 5'-G CCB TBG CGB GGC TGB G-3' (FRAG. NO: 1733) (SEQ. ID NO: 1746) 5'-CTC TGG GGT GGC CTT C-3' (FRAG. NO:1734) (SEQ. ID NO:1747) 35 5'-GCG CGG GCC GGG GGC TGC TGG G-3' (FRAG. NO:1064) (SEQ. ID NO:1072) 5'-GGT TGG CCC GGG GTG CCC C-3' (FRAG. NO:1065) (SEQ. ID NO:1073) 5'-GCC GCT GGG TGC CCT CGT CCT CTG CGG TC-3' (FRAG. NO:1066) (SEQ. ID NO:1074) 5'-GTG TCT CCT GGC TCT GGT TCC CC-3' (FRAG. NO:1067) (SEQ. ID NO:1075) 5'-GCT GCG CCC GTT GTC CTC TGG GGT GGC CTT C-3' (FRAG. NO:1068) (SEQ. ID NO:1076) 40 5'-GCT CCC GGG TCT GGT TCT TGT GT-3' (FRAG. NO:1069) (SEQ. ID NO:1077) 5'-TGG GGG TCC CTT' T GGG CCT GTT GT-3' (FRAG. NO:1070) (SEQ. ID NO:1078) 5'-GGC GTG GCT TGT GTG TTC GGT TTC-3' (FRAG. NO:1071) (SEQ. ID NO:1079) 5'-TGC CCT GTC CTC CGG CGT CCC-3' (FRAG. NO:1072) (SEQ. ID NO:1080) 5'- CGG BGC CTC CCC GGG GCB GGB TGB CTT TTG BGG GGG BCB CBG BTG TCT GGG CBT TGC CBG GTC 45 CTG GGB BCB GBG CCC CGB GCB GGB CCB GGB GTG CGG GCB GCG CGG GCC GGG GGC TGC TGG GBG CCB TBG CGB GGC TGB G-3' (FRAG. NO:1073) (SEQ. ID NO:1081) Human Vascular Cell Adhesion Molecule 1 (VCAM-1) Nucleic Acid and Oligonucleotide Fragments 5'-CCT CTT TTC TGT TTT TCC C CTC TGC CTT TGT TTG GGT TCG CTT CCT TTC TGC TTC TTC C CTG TGT 50 CTC CTG TCT CCG CTT TTT TCT TC GTC TTT GTT GTT TTC TCT TCC TTG CTG BGC BBG BTB TCT BGB TTC TGG GGT GGT CTC GBT TTT BBBB GCT TGB GBB GCT GCB BBC BTT BTC CBB BGT BTB TTT GBG GCT CCB BGG BTC BCG BCC BTC TTC CCB GGC BTT TTB BGT TGC TGT CGT-3'(FRAG.NO:1735)(SEQ.ID NO:1748) 5'-C TGT CGT-3' (FRAG. NO:1736) (SEQ. ID NO:1749) 5-TGC TTC TTC C-3' (FRAG. NO:1737) (SEQ. ID NO:1750) 55 HSVCAM1AS1: 5'-CCT CTT TTC TGT TTT TCC C-3' (FRAG. NO:1074) (SEQ. ID NO:1082) HSVCAMIAS2: 5'-CTC TGC CTT TGT TTG GGT TCG-3' (FRAG. NO:1075) (SEQ. ID NO:1083) HSVCAM1AS3: 5'-CTT CCT TTC TGC TTC TTC C-3' (FRAG. NO:1076) (SEQ. ID NO:1084) HSVCAMIAS4: 5'-CTG TGT CTC CTG TCT CCG CTT TTT TCT TC-3' (FRAG. NO:1077) (SEQ. ID NO:1085) HSVCAMlAS5: 5'-GTC TTT GTT GTT TTC TCT TCC TTG-3' (FRAG. NO:1078) (SEQ. ID NO:1086) 60 CTG BGC BBG BTB TCT BGB TTC TGG GGT GGT CTC GBT TTT BBBB GCT TGB GBB GCT GCB BBC BTT BTC CBB BGT BTB TTT GBG GCT CCB BGG BTC BCG BCC BTC TTC CCB GGC BTT TTB BGT TGC TGT CGT(FRAG. NO:1079)(SEQ. ID NO:1087) Human Endothelial Leukocyte Adhesion MoleculefELAM-1) Nucleic Acid and Antisense Oligonucleotide Fragments WO 00/62736 PCT/USOO/08020 146 5'-BBG TGB GBG CTG BGB GBB BCT GTG BBG CBB TCB TGB CTT CBB GBG TTC TTT TCB CCC GTT CTT GGC TTC TTC TGT C CGT TGG CTT CTC GTT GTC CC TGT GGG CTT CTC GTT GTC CC CCC TTC GGG GGC TGG TGG GGC CGT CCT TGC CTG CTG G GTT CTT GGC TTC TTC TGT CCG T TGG CTT CTC GTT GTC CC TGT GGG CTT CTC GTT GTC CC CCC TTC GGG GGC TGG TGG GGC CGT CCT TGC CTG CTG G CCTGAGACAG 5 AGGCAGCAGT GATACCCACC TGAGAGATCC TGTGTTTGAA CAACTGCTTC CCAAAACGGA AAGTATTTCA AGCCTAAACC TTTGGGTGAA AAGAACTCTT GAAGTCATGA TTGCTTCACA GTTTCTCTCA GCTCTCACTT TGGTGCTTCT CATTAAAGAG AGTGGAGCCT GGTCTTACAA CACCTCCACG GAAGCTATGA CTTATGATGA GGCCAGTGCT TATTGTCAGC AAAGGTACAC ACACCTGGTT GCAATTCAAA ACAAAGAAGA GATTGAGTAC CTAAACTCCA TATTGAGCTA TTCACCAAGT TATTACTGGA TTGGAATCAG AAAAGTCAAC AATGTGTGGG 10 TCTGGGTAGG AACCCAGAAA CCTCTGACAG AAGAAGCCAA GAACTGGGCT CCAGGTGAAC CCAACAATAG GCAAAAAGAT GAGGACTGCG TGGAGATCTA CATCAAGAGA GAAAAAGATG TGGGCATGTG GAATGATGAG AGGTGCAGCA AGAAGAAGCT TGCCCTATGC TACACAGCTG CCTGTACCAA TACATCCTGC AGTGGCCACG GTGAATGTGT AGAGACCATC AATAATTACA CTTGCAAGTG TGACCCTGGC TTCAGTGGAC TCAAGTGTGA GCAAATTGTG AACTGTACAG CCCTGGAATC CCCTGAGCAT GGAAGCCTGG TTTGCAGTCA CCCACTGGGA 15 AACTTCAGCT ACAATTCTTC CTGCTCTATC AGCTGTGATA GGGGTTACCT GCCAAGCAGC ATGGAGACCA TGCAGTGTAT GTCCTCTGGA GAATGGAGTG CTCCTATTCC AGCCTGCAAT GTGGTTGAGT GTGATGCTGT GACAAATCCA GCCAATGGGT TCGTGGAATG TTTCCAAAAC CCTGGAAGCT TCCCATGGAA CACAACCTGT ACATTTGACT GTGAAGAAGG ATTTGAACTA ATGGGAGCCC AGAGCCTTCA GTGTACCTCA TCTGGGAATT GGGACAACGA GAAGCCAACG TGTAAAGCTG TGACATGCAG GGCCGTCCGC CAGCCTCAGA ATGGCTCTGT 20 GAGGTGCAGC CATTCCCCTG CTGGAGAGTT CACCTTCAAA TCATCCTGCA ACTTCACCTG TGAGGAAGGC TTCATGTTGC AGGGACCAGC CCAGGTTGAA TGCACCACTC AAGGGCAGTG GACACAGCAA ATCCCAGTTT GTGAAGCTTT CCAGTGCACA GCCTTGTCCA ACCCCGAGCG AGGCTACATG AATTGTCTTC CTAGTGCTTC TGGCAGTTTC CGTTATGGGT CCAGCTGTGA GTTCTCCTGT GAGCAGGGTT TTGTGTTGAA GGGATCCAAA AGGCTCCAAT GTGGCCCCAC AGGGGAGTGG GACAACGAGA AGCCCACATG TGAAGCTGTG AGATGCGATG 25 CTGTCCACCA GCCCCCGAAG GGTTTGGTGA GGTGTGCTCA TTCCCCTATT GGAGAATTCA CCTACAAGTC CTCTTGTGCC TTCAGCTGTG AGGAGGGATT TGAATTATAT GGATCAACTC AACTTGAGTG CACATCTCAG GGACAATGGA CAGAAGAGGT TCCTTCCTGC CAAGTGGTAA AATGTTCAAG CCTGGCAGTT CCGGGAAAGA TCAACATGAG CTGCAGTGGG GAGCCCGTGT TTGGCACTGT GTGCAAGTTC GCCTGTCCTG AAGGATGGAC GCTCAATGGC TCTGCAGCTC GGACATGTGG AGCCACAGGA CACTGGTCTG GCCTGCTACC TACCTGTGAA 30 GCTCCCACTG AGTCCAACAT TCCCTTGGTA GCTGGACTTT CTGCTGCTGG ACTCTCCCTC CTGACATTAG CACCAT'rTCT CCTCTGGCTT CGGAAATGCT TACGGAAAGC AAAGAAATTT GTT'CCTGCCA GCAGCTGCCA AAGCCTTGAA TCAGACGGAA GCTACCAAAA GCCTTCTrAC ATCCTTTAAG TTCAAAAGAA TCAGAAACAG GTGCATCTGG GGAACTAGAG GGATACACTG AAGTTAACAG AGACAGATAA CTCTCCTCGG GTCTCTGGCC CTTCTTGCCT ACTATGCCAG ATGCCTTTAT GGCTGAAACC GCAACACCCA TCACCACTTC AATAGATCAA 35 AGTCCAGCAG GCAAGGACGG CCTTCAACTG AAAAGACTCA GTGTTCCCTT TCCTACTCTC AGGATCAAGA AAGTGTTGGC TAATGAAGGG AAAGGATATT TTCTTCCAAG CAAAGGTGAA GAGACCAAGA CTCTGAAATC TCAGAATTCC TTTTCTAACT CTCCCTTGCT CGCTGTAAAA TCTTGGCACA GAAACACAAT A'ITTTGGC TTTCTTTCTT TTGCCCTTCA CAGTGTTTCG ACAGCTGATT ACACAGTTGC TGTCATAAGA ATGAATAATA ATTATCCAGA GTTTAGAGGA AAAAAATGAC TAAAAATATT ATAACTTAAA AAAATGACAG ATGTTGAATG 40 CCCACAGGCA AATGCATGGA GGGTTGTTAA TGGTGCAAAT CCTACTGAAT GCTCTGTGCG AGGGTTACTA TGCACAATTT AATCACTTTC ATCCCTATGG GATTCAGTGC TTCTTAAAGA GTTCTTAAGG ATTGTGATAT TTTTACTTGC ATTGAATATA TTATAATCTT CCATACTTCT TCATTCAATA CAAGTGTGGT AGGGACTTAA AAAACTTGTA AATGCTGTCA ACTATGATAT GGTAAAAGTT ACTTATTCTA GATTACCCCC TCATrGTTTA TTAACAAATT ATGTTACATC TGTTTTAAAT TTATTTCAAA AAGGGAAACT ATTGTCCCCT AGCAAGGCAT 45 GATGTTAACC AGAATAAAGT TCTGAGTGTT TTTACTACAG TTGTTTG AAAACATGGT AGAATTGGAG AGTAAAAACT GAATGGAAGG TTTGTATATT GTCAGATATT TTTTCAGAAA TATGTGGTTT CCACGATGAA AAACTTCCAT GAGGCCAAAC GTTTTGAACT AATAAAAGCA TAAATGCAAA CACACAAAGG TATAATTTTA TGAATGTCTT TGTTGGAAAA GAATACAGAA AGATGGATGT GCTTTGCATT CCTACAAAGA TGTTTGTCAG ATGTGATATG TAAACATAAT TC17GTATAT TATGGAAGAT TTAAATTCA CAATAGAAAC TCACCATGTA 50 AAAGAGTCAT CTGGTAGATT TTTAACGAAT GAAGATGTCT AATAGTTATT CCCTATTTGT TTTCTTCTGT ATGTrAGGGT GCTCTGGAAG AGAGGAATGC CTGTGTGAGC AAGCATTTAT GTTTATTTAT AAGCAGATTT AACAATTCCA AAGGAATCTC CAGTTTTCAG TTGATCACTG GCAATGAAAA ATTCTCAGTC AGTAATTGCC AAAGCTGCTC TAGCCTTGAG GAGTGTGAGA ATCAAAACTC TCCTACACTT CCATTAACTT AGCATGTGTT GAAAAAAAAA GTTTCAGAGA AGTTCTGGCT GAACACTGGC AACGACAAAG CCAACAGTCA AAACAGAGAT 55 GTGATAAGGA TCAGAACAGC AGAGGTTCTF TTAAAGGGGC AGAAAAACTC TGGGAAATAA GAGAGAACAA CTACTGTGAT CAGGCTATGT ATGGAATACA GTGTTATTTT CTTTGAAATT GTITTAAGTGT TGTAAATATT TATGTAAACT GCATTAGAAA TTAGCTGTGT GAAATACCAG TGTGGTTTGT GTTTGAGTTT TATTGAGAAT TTTAAATTAT AACTTAAAAT ATTTTATAAT YTTAAAGTA TATATTTATT TAAGCTTATG TCAGACCTAT TTGACATAAC ACTATAAAGG TTGACAATAA ATGTGCTTAT GTTT GATCAAAATT TTTACCTATT 60 ATGCATTTGA TATATAAATA AGTATATAAA TGCACACACA GACACAGCAA TGATGGTGAA CAGTCTTCAT ACAATTATAT GGATGAATCT CATAAAATGC TGAGTTAAAG AAATCAGACC AAAGAACATA TACTGAAAGA TTICTCTCTAT ATACAAAGTT CAAAAATAGG TGGACCAATT CATGGTGGTG TTAGAAATCA GAAGAGAGGC TACCTTTGTG GGGAGGGGAC AGTTTAATGC CCAGAAGCGG TAAATAAGGA ATCCTCTGGG GAGTGGTAAT GATCTGGATG CTGGCTACAG GATGTGTTGG TTGTAAAAAT GCATTTTTTT ATATCTAGCT TTTTCCATGT 65 GTATATTATA CTTCAAAGAA GTTCAGTTAA TAATTT'CTCA TGTCACTGTA GAGTAGCTCA GTFAGCCCCA GCAAGCCTCT GGCTTAATCT TGTTTTACCT TAAGCCATCA GTCATTTACA AGTAGGAAAA TTCACAGGGA WO 00/62736 PCT/USOO/08020 147 AAG FJ7AGAGT ATAAAATCCA GAATGAAGGT TFTACTGGGTA AGAGTCTCTC CA'TI1'rCCAA AGCCCG'ITTA 'IMCTrGATF CCAGTTCTTA AGAAGTCTCA GCATTGTGTC TTTCATGT ATCTrrACAAG AAGACAGCAT GTGCTTCTAA CACCTGATAC ATTGTATCTA CCAGCACTTG GTAAACAGAA AAGAACCACA YFITrC'rrGT AGGAGAAATT TGGTGCCTAT TI7CCTACCAG GCACCAATAA GTGGGACCAA TAGGTGGGAT TAAAGATACA 5 GTAGAAAGTA =IAAAACTT GCCAGGGGGC AATAGTCTGA AAATAAGTAA ATrGGTGCTA TAGAATGGAA GTTACAGGCT TC'ITCT=T TTCCCACAAG ATCTGCTCCT TGAGCCCCTA GAGACTITC TGTCTGTTAC TGTFTCTTCA TTCCTCATCT GCAGAGCCAG CCCTGAGAAG TGCAGACCAA AGCCAGGGAA GGCTCTGCAA AGATGTACAA ATGGAAGTCA CCTTAATAAC CTCTGACTGC TGCGCATAAT ACA'ICACT CAAAAGAGGG GTTrAAACAAT GGAACAGAAT ACAGAGGCCA GAAATAATGC TGAACACTGA CAACCATCTG ATCTJTGACA 10 AAATCCACAA AAACAAGCAA TGGAGAAAGG ACTCCCTATT CCATAATGGT GCTGGGATAA CTGTCTAGCT ATATACAGAA GATTGAACCT GGGCCCC117C CTTACATCAT ATACAAAAAA TAACTCAAGA TGGAGTAAAG AC'ITAAATCT AAAACCAAAC ACTATAAAAA CCCTGGAAGA TAGCCTGGGA AATACCATTC TGGACATAGG ACCTGGCAAA GA=TCATGA CAAGACACCA AAAGCAATAG CAACAAAAAC CAAATTGACT AATGAAACTA ATGAAACTCT TTAGTTGTAC AACAGATAGT TTIATCTGTAC AACAAAATAA ACTATCAACA GAGTAAACAA 15 CCTACAGAAT GGAAAAAITT TTrGCAAACT ATGCATCTGA CAAAGGTCTA ATATCCAGAA TCTATAAGGA A ITTAAACAA A TTACAAGC AAAAAAATGA CCTCATTAAA AAGTGGGCAA AGGACATGAA CAGATGCITI TCAAAATAAG ACATTCACAC ATCCAACAAC CATATGAAAA GATGTJTAAC ATCACTAATC A'TTAGAGGAA TACAAATCAA AAGCATAATA AGATACCATC TAATACCAGT AGGAATGACT ACTATTAAAA AGTCAGACAA TAACAGATGC TGGTGAAGGT TGTGGAGAAA AGGGAATGTT TATGCACTGC TAGTGGGAAT GTAAACTAGT 20 TCAGCCATTG TGGAAGAGAG TGTGGTGATT CCTCAAAGAA TGTAAAACCG AACTGCC'Tr CAATCCAGCA ATCCCATTAT TGGATATACA CCAAAAGGAA TAGAAATTGT M1IACCGTAA AGGCGCATGC ATGCATATGT TCATTACAGC ACTA'ITTACG ATAGCAAAGA CATGGAATCG TCTAAATGCC CATCAGTGGT AGACTAGCTA AAAAAAAAAA AATGTGGTAC ATATACATCA CAGAATAGTA TGCAGCCATA AAAATGAACA AGATCATCAT GTCC'ITGCA GCAACATGGA TGTAGTIGGA GGCCATTATC CTAAGCAAAT TAATGCAGGA ACAGAAAGCC 25 AAATACCACA TGTrCTCATT TATAAGTGAC AGCTAAATAT TGAGTACACA TGGACACAAA GAAGGGAACA ATAGACATGG GACCTAC'rG AGAATAGAGG GTGGGAGGAG GGTGAGGATC AAAAAGTACC CATAGGACAC TGTGCTATT ACCTGGGTGA TGAAATAATI' TGCACACCAA ACCCCTGTGA CACACAATrT ACCTATATAG AAAACCTGTG CATGTACCCC TGAACCTAAA AGUTAATGGT GGGGGGGTGG GGTTAAGCTA C'ITGTGGTA TAAATCTGAG CATTCATATT AAAATAAAAT A FITACCTCA T7AGAGTAAT TAACAMTAT TAAGCAAAGA 30 GCCAAGTACC TTACACACAT GATG'TAAT CTCACAATGA TC'1AATCT CATAACAACC GTCCA I1GTA TGTACATATG TGGAAATTGA GCCTTGGAGA GAY7AAATGC ATGGGGCATG CCATTTGACT AGAAACTGGA AGCATCAGGA 'LTAAACTCA GTTCTGAATG G=TGTAGG CTITG'TIT TCCACATTAT AGCATGGCCT GCCATGAAGA ACAGGTCCTT TCTGGTGTTT GTCTrG'TrG GTI17AAGTGA AGCAAATATI7 TA1TTAAATA 'ITCAAGATAT GCTGTTAAAT 'TTTACTCAA AAATTTGAGT ACAGTATGGA TCITCTGAAG CCAAATAACT 35 C FAiTCAAT GCTTAGTTGA GAAATITAT GGAGTAGTTC TCAAITTA TGTAGTTCCA CTGCAAAGGT AAGTC'ITATG GAAAGATTCA CTGTAATT 'rITrCCTCAT TTGGACATCA GCITTTrCTT TTCCTCAGAC CCGCTGAAAG ATAATTrTA AAATAAAAAC CTrTIrrA TATCAAGTGG GGACATTr TCCAAATGAA AACCGTGTAT TCAT1TATA TGATAAAATC AATGTTATrA TTMAAAAT TITGA'TTTAA AAATCATTIAA AAATAAATTT TCAGATATTA CCTGAAATTC TACCATCCAG AGATAATAGT GCTTAAAGAT TTGATATATA 40 GACACACACA CATATATACA TATATATCAT CCTAAACTTC TITGTATAAA TGTATATAAA GTITIAATA AAAACTAGGA GA11'AATGCC CITr1GAATGA AAATAAATAC AATGTGTATG CTAACATC TrGCC'ITTAC TITATAACAT 'ITATCACAGC AGTCATGAGA TAATGAT~rA CATGGTCA'I7 G TTAGTAAGC TAATAGCTAA GTGCATGAAC TCTGGAGCTA GCCTCCCTGG A IIAATCC CAGATCTGTC ACTGACCAGC TGAGCAATAC TAGGTAAATT GCTCTTGTTC CTrAGTCT TCATCTGTAA AATAGAGATA AAAATAATAT CCACCTCATA 45 GGAT]TGGTGT GAGCATTAAA TGAGCATACG TATGTAGGCC ACTTAACAAC AATGCC'ITCA CATACTGAAC ACAAATATAC GAGCTGTTGT CTTATrGGGC TCATGTITT CCTACCACTA AGCCGCATGC ATGCAAGGAC CATGTTGGTT TTfGTTCCACA TTGCATCCCC AACCTGGTAT ACAGTGTGCA TTCAATAGTT G'rrGACTATIT ATTACTAGTG GCA'IMAACA AATATCTGTT AAATGAGTGA AGAAATACCC A'ITTACTGCA AGTGTGTCTA ATATTGATGG CATAATGGGG GAAACTCAAA CTCTGGAGTC AAACAGGT TAAAACCTTA TTCCCTCATC 50 CTCAGTI'ATr GACGTTIT T'ITGGCAGG TGTGTGTGTG GGACAACTrA YFGAACTIT CTGAA'1TTCC AGC FTCGCAT ATATAAAATA GAGATAGTGA TTCATrC'rrG CAATGTATGG ATrTGAGACA ATTGTGTAAG TP'TATCAATA AATAGTAGCT ATITTGTAT AAGTATI1ACA TATAATATCC AGGCCACTGC 'TrTGCATAAC CCAAAAGGGG CACCATTCAT GCAGAATACA ACATAAATGG TGTCCCTGGA GCAGTGCAGT ATAGGAACCC TGAGGGGACC TACAGTATAC TTTATAGTT1C ATAGAT7ACA AA'I1ATCCCT TTATCAGAGT CTCTCAAGGT 55 TGGATGTATT TGAGGTCCAT AAGAGCAA2FT TAGGATTAAC AGTAGCTGCA GAAACCATCT GCAGTGATAT TCTCA=1VA AATCCGCGGG AAAGAAGACA GCTATAAACT TGGGACCTGG G TrAAGCAT MhAAATGCC AAGTI'CACCA rTMCTAAAA CACAACAAAT ACCCAGTGAG AGAGGGAGAA GGGAAGTAAA TGCCTCTGAA TAAGCAAGI17 AATGTCAGTA GYTGTACTGT ATGCATATrG ATGAACAATA GAGGAACCAA TGTCCAATCA GATGAGCAGG ATA TI'GGCA ATAACAAG'IT GCC'TrGAGG AAAAATGATT TTCTTGGCAA GTTCTITATC 60 AGCATTACAA AGCTAAAAGC TACGCTTATC ATCACTTATA CTAGCATACC CTGYPGTGCA AATGCTGTCT GTGTTTGCAT CTGCTATTGT TGATGCCTGG TGCATGAATC AGGACTCCAG CCCACAAGrr TT1CCCAGAAC M1T'TATGG CCATCATCTT TAAGTGTCTG GTGAACAGTC ATAGTTTGGT ACACAAAAGG GTCAACCTGG GGGATGGCTA GGGTITGACT CAGTCGTTAC A'TrTCAATAG AGCAGGAAGG GGAAATGGTG GCCTGTAACC TCAGGGAATT 'rrGCCAGVrG GTCCACCCCA CTCTCTCTCT CCTGCTCTGA GGAAGTGGCA CAGCCTAGAA 65 CAGCACCACA GGTGAGAGAA ATGCAAACCC TAACCAGAGA AGCAGACTCT Y~rGCCAGTAG TAATAGTTCA GGACCACCAC CAGCTTAT TAAAATI1T AATAACACTC AAGTATTGGC AGAAAGAAAT AATCTTGGGT WO 00/62736 PCT/USOO/08020 148 TAACTATAAC TAGAATATTG ACTCTTCCTC TGTGGAAGAA TCAGCCAATC ACATTTGYTT ACATCAGTTC CCCTGAAGAA GAAAAATACA CTGATGTrGC AGCAAGACAA ATTTAAGCTA GATGTAAATA AC'FrCC'FrTA GCCTGTAATG CTAGGCTAAT TACATAT7IGG AACTAT=1T TCAGGGAAGA ATTGTGTAGG GMTCAGGGA AGAATTCTGA AGAAAATATA GAGCTGAAAT GATCTTGCAG CTCACTGAAA CTGCAGGGTT TAGATCCACA 5 CTGATACTCG TTCTAT7ATC ACTGTAATGA AGGCTGATGG AATAAGTAAA AATGY1TGT ATTAGTATGT TITrACAC'Fr ATITTGCAAGG CATAAATAGG 'FTAGGTI=G ATCTTAA'Tr AAYrCTAACA TGTATTGTGC ACAAGCTGTG AGCAG=L~C AGGAGflAGG TATCTGGCCA TGACTGAT TTCAGGAGTT AATCATCTGG TAGAAGGGTC ATACACAATA GGAAGATGTG TGTGACAGGT TGTGATCATT ACTATAATCA CACAGAGAGC TGTAGAATTT TAGGCTGGCA GGGTGGCTCA CGCCTGTAAT CCCAGCAC'IT TGGGAGGCCA AGGCAGGCGG 10 ATCAAGAGGT CAGGAGATGG AGACCATCCT GGCTAACACG GTGAAACCCC GTCTGTACTA AAAATACAAA AAAAAAAAAA AGCCAGGCGT GGTGGTGGGC GCCTGTAGTC CCAGCTACTT GGGAGGCTGA GGCAGGAGAA TGGCGTGAAC CCGGGAGGTG GAGCTTGCAG TGAGCCGAGA TCGCATCACT GCAATCCAAC CTGGGCGACA GAGGGAGACT CAGTCTCAAA AAAAAAAAAA AAAAAAAGTC ATG FTAGATC CAGAGGGGTA GCAACTGGGG CTGGGCTGTC AGTCAACTCA GTCAACTCAG TCAACTCTGC TCCCCCACAG GAGATGCCAG TGATGCATrT 15 TCATGGCCAA CAYTGTCAGT CAGCATCA317 GAA'I1ACTCC TGATTATAGA GACACAGCTG CAAACGAPI'C CCCATTAAAT ATGATG'ITTC TT1GCAATGL1 TGGAAGGTAC TCC'TTrAG TAAGGGAAAT CCCCTCrrCT GGCTTGCTGA AAGTTITC TTTCCA1TI AAAAATCGTG AATTCCTIT TGCAATA'rTG AGGTGGTTAT ATGGTI'TCTC TITCTCTAATC TGTTAATATG GTGA'ITAAT GGTTAGAAAT TITCTAATGT AAATTCCACT CATATJ7GCAG AAATAAACCT AAACTGAGCA TGAGGCTATA TIT=TTT~ GCTTCTATAT TTGGTTGCTA 20 TACAGTATTA TGMTAAGAT TTGTTCACAT ATATY1TGTGA ATGGGATL7GG ACTA'TrrrTC C'rrCTrGCCG AYTTATCT GGT=I]AAA T-FAAGGATAT TAGACTrA TGAAATA'TrT GGCAAACAAT CCTTGGCAAG TAA'TTTTG GGGAAT1'GT TTI'GGCTATT TTGAGTATTA CCCAATATAT 1TI'AATL'AAG TTATfCTTAA TGTIT TA ATTAAAAAAA TI'ACCTACTC TAGAGATATT CTITATGTAC TCCAGATMT GTCTATITAT ACCACT=TC 'TT11CCTC GATGAGTGTC ATAGATGTTC ATCTATIT TTATCTrTr TGATCTTCTC 25 'rrATTCCTTG ITTCTATTAA CTTCTGAAGT TTATTATT C'TT1TCCA CTTCCTTATG GTITAT[CTT TCAATITJC TCTAACI1CT TAAG'ITGGGT GTIT7AATIT TAGC ~rGCTT TGCTTITPA GGATAAGCAT TAAAACTACA AA ~17CCTT GT7AfTT= TGCTGCACCC CAAATTGTTrG ATA1TTCTAT TGTCTAMTT CTAT'TCAATT AGAATACTTT AAAGTCTT TTTGGITT= AAAAACTAAC 'PITfrAAATT GACAAATAAA AA F7GTGTAT ATTTATTGTG CACAGGATAT GGC=fGAAA TATATGTACA T[rGTGGAATG GCTAAATITA 30 GCTrATTAAT GTATGCATTA TCTCACATAC T-FATCATT TI'GTGGTGAG AGCTATGTGA CYTI'rGAACT TATGAGTTAT TTAAATATTT TTAAATTATT AAGCATATTG GGATITAAG TAA TTACCT TTATrArrT AACTTATAAC AAGTAGAACA GTI'AACCTGT ATGATTCTAC ATCATTGAAA 1TATTGACA TrTGCTrCAT AGTCTATTAT ATGGTCTACT ITTGTrCATG 'TACATCTGT AGTAGAATI'G GCTAATAGTT GAGTAAAGTA CACATATGTC TATGAAATCA AGTGTAATCC AGAGAAAAAG AGAAA ITAC TGAATATA11 GFTCTAGGTG 35 CTATTATATG TTGTCATGTYF TAATCCTCAC CACAATTGTA TGAGGCAGCC ATAA'PTAATT CCAC'ITACA CATGAGGAGC CTGAGGGTI'A AAAAAAAAGC TAGCTCTACJ? ATTTGTAAAG AATGAAGCAA AGATACAAAT GAAGGCCCAC ATATCCTATA ACTAGATALT TAAGCATfIT AATTCAAGCT 'I1AAAACTGC TAAATAAAAT GTGCTCCAATTTCTATATTG ACAGACATAC CTTCCTAATG AGCTGGGGTT CGAA'TrAGA AATCTITGAT GCTTCAGAGT CCACACTGAA ATGTGGAGGC ACATAGTGAG TFGGTCCCCA GCCTTCAGTC CACCCACCTT 40 CTCTI'TACTA AATCACCTT. CACATACATG TATGAACACC CCAGCCTCCA AGTCCAAACC CTAAACAAAA TGGGACACCC TTGTGCATAC ACAGAGACAC AGCCCATCCT CAGGAAAACC TGGAAAAGTC CATACAAGTT CTGGAAGCAA GCTTGGGACG G1TCAGTAG TGTGGTCTAT AAGGGAGGCC TCAGAAGACA GGYM~CTTA AY[CTGTGAA CTTCTCCCAC AGTAGAAAGG GTGCTGGAGG AGGGTCAGAG TGAGGAC11C TAAAGCATGG GTCCTGAGTA GGGGCCACTC TrGCCCAAGT CTAAGAAGGG TACTAGAATA GCACACTACT ACTAGATACT 45 AGAACCCAGA TACAAGCACA GGTCTCTGA AATTAATAAT AATAATAACT ATTACCA FTA TTATACCAGT AGCTGTCATT TAMrAGTGC TTATTA'ITTG CCAGTCACTG TTCTAAATTC 'ITI7ACATGTA TTATACAACT GCCATATAAC TGCCATATGA GGGATGTACC CTCATTGTCA CCATTACC GATGAGAAAA CTGGCATAAA ACGTITAAGT AACTTGTCCA AGTTACAGAG CTTAGTGAAG CCACAATGUT GCTCAA=PG CTCTCAAACT TCAAAGGGAT GGGAAGGACA CCTAAGTCAT AGAGTC'ITA AGAATCAGAG CTAGAAGGAA TCTTAGATGT 50 TATCTAGTCA GCCTCCTCCC ATTACAGTCC AAGAGAAGAT GGCCCTGAGT TACTTGTAGC TATT=GCA TGTGAATTGC AAGTGAATAT ACATTCTACT GAAGATAAAA GATA TTAAA GATATCGCTG GATATAGGAA CAGTGGT'Tr AAATCTCTAG GC'TrAACTT TTCTCAGAAC AAGAAATCCT TITGGTIT AATCTATATG CACATCTGTA TTITTTCTCAA TTATCGGGTA GTAAAATATA ACTTTrC TGTAATATrT T'rrAAC=rA ATGAGTGTTrC CTCATAATAG AAAAG ITGG AAACCA ITGC TATGGGTATA TACTTTCTAA AGGGATAGTA 55 A'TTCTCTAG AATATTCATT TAATGCTCCA GAAGTAATTA GCACAATrGT GCAAGTCTGT GCATCATCAA CTATACATTC TGCCTGYPTA CTCCAAATCC ACATGAAACT GA117ATACAG TCAAAGGCGA GCCCAGTGGA GAGGCAml TGGAGACTTC CTGGTACATT GAGACAGGGT CGGCCAGTCT GCGTTAGGGT CTrGGTCAAA ACTGCATTTC TGAAACTAAA CTCAGATTGC 'TrCTITTAA GGGGTCAGAA CTGATTCAAA TCTACAT= TAAAAGCCTT AGATGTGGGG CTITCCTAT TCCCAGTCTC CGCTATTGGT C'TGTGAAT CCACAGGCAA 60 'TTTGGCCACA TCCTTGACTC TCTC'ITATAT TAAGAATTAA ACAGCTAAGT TCATGCAGAG GAAATATAAC AAAGGAGGGA CTTTCCTACA AGATCTrGA AAAATGGAAC ATrGCATAA GTCATA'ITTA GCCAGAACTG TTG TT7ATA rrrCC-rrrC TGAATACTTT GT7ACACCTC CTCCCAGCCA ACCCCCCCCC TCCCTGACCC CAACTAGTCA GAGACCAAAG CCTTCACAAT GG'IMACACT TGAACCTTCC TGGCCCCACC CTCATCATCA CGCCTGAATA ATI1ACATI7CA CTGACTGGTC TCCCCTGC117 CCGTrATCT CCACTCCTAA ACCCTCTGAC 65 ACC'FTAATCT TCCCAGAATA CCATTGTGAT CCTGTTCCAC TC'I1GCTCAA G=TCCCAG AAACTAGAGT ACAAAC'rfrA TAAGCTI1?AG AGTTGAAAGC CACTCTATCT C'TTMCATC CCCAGGTCTC TGCCAAGGCA WO 00/62736 PCT/USOO/08020 149 GTATAACCTG TCCAACATCT CTAACTTCAA TACCTGTC TTAGATACTA GACTCTCCTC CTGGTTTCTA A~TAAACCTG ATCTAGGATC TAATITTGCC TCTGAATI'CT GTTGCCCTI GCCAAGTGAT CTCTFCCTCC TCTGAGCCGC AGCATCTCTG AGCTTGCACA C'rTAGCATAG CCATAGCACA CACAGCCTTrA GCTrGCAGTr CAGGGTGTTT ACCTrCCCTC CCCTTCCAGA TGCTGGATCC CCAGGGATAG GAACTCTGCC CTTATGTGTC 5 CATAGCCCCT GGTAGTATGT CTTGCAGTCG TACATTPCA GCAAATG Tr AATTGGI1'AA TTGAAGACAA CTGTCCCATG CCTTAAGCCT CTCTrTGC TAAACATGCC TGTGTCCTIT GTCATTGAAC AACTAFTT~G ATCTATTC TrCCTGACAT AGGGGTCAGT TCCGAGGATG CTGAAATCAA GAGACATAGC TTATTCTCTC AAAATTrGCTr TCAAGAGTGA TMTGT-TGTG AATTGAGAAC TGGCTGCCTA CTITfGGACT ACCCACTrCA GCAAGAGTGT 'FrGAAACCAA ATCTATTCTA AGTAATTI TATrCCC'Tr TCTCTATGGC ATTAGACACA 10 CAGCTcTTr AAACTACCTI' TCGTTATCTA TTAAACAGAC ATrCAGTAAC TCTATAGACA CTGTCTAGCT ATATGAACTI' AGACAAACTA ATATCTCTGA GCTTCAGTTT CTTAAAA1TI AAAATGAGGA CAATACCATC TATGGCCGGG GATTAAATGC TATGAGGAAT GTAAACCAGA TGTCAGGTAC CATCTCTCTA AAATCCAGAT AAAATGAATT AAAAATACTG GCCGCAAACC CTCTCTAAGA GTTCTCAAAA TrCTCAGAGA GCTTAATITr CATGCTCACC ATAGCACCGA TTTTCTTCTA AATA=flGT TTCTACCAAA ATA'I1TTGTC CCAATITTGC 15 CTTATGGC TTT-rcTrCA TATCCACTTT CCCAAAG TAA AGAAGCAGCC CCTTCACcT AAACTCCTCC '1CAAAGCAA CCTAAATACA GGTCTGGGTT TGTATTCCTA GTGGGATGTT ACAGAGGTTA GTGTGATGCA GAGGAGGAGT CATGCTGTI'T AAATCCATAC TAGTCCCCAG AGGCCAGGCT GC'ITCTGCCA CCCCTACCCC TCCCGCCACA GAGCTCTTCA GCTTCTCACA TITCTAGTTC TrCTCTCTCT ACTrCATTA CCTTCTCTCT TlTrTTr CT7CTCATGT GCTCACGGGA GCAGAGAAAA TrAACTCCTC TAAG FT=CT TAACACAGAG 20 TGCCTT1AATT ACATATrACT ATTGTTTGAG TTCCTGCCAA CACTACGTCT GTAGGGTCAC ACCTGCTATA TTAGAGGCT'F ATCAAAAAAA GATAGC'T'C TCCTAAAAAG GGATTTGGAT GCCTACTAAG ATAACTGGAT GCCAAGATAA GTTTAACCTA ACAAACTA FfATTA FTAT TATrA'rrArr ATTAGAGATA GGTACTTATT CTGTCACCCA GACTGCAGTG CAGGGATGCA ATAATAGCTC ACTGCAGCCT CAAAGTCCTG AGTTCATGCA ATCCTTCTGC TT1CAGCTCCC TGAGTAGCTA GGACTACAGG CATATGCTAC TCTGCCCAGC TACTTAAA 25 AAAATAATTA GGGATGGGGT CTTGTTGTAT TGCCCAGGCT CGTCTCAAAC TI7CTGG=IC AAGCAATCCT CCTGCCT1T ACCTCCCTAA FTGTTGiGAGT TACAGGCATG AGCCACAGCA CTCAACCAAG ATFTAAAAAC T=~AAAAGA AATCACA ITA CT-rACTGTTA TCATCATTAT GGT7ACTACC AGTGTTAAAA CAA3TGGTAT TGAAAACACC ACTACCAGAT CAAGCTICAA ACCAAGATGT CAAGTAAATA TTATTGTCAG ACCTCTGAGC CCAAGCCTGC AGGTATACAC CCAGATGGCC TGAAGCAAGT GAAGAATCAC AAAAGAACTG AAAATGGCCG 30 GTTCCTGCCT TAACTGATGA CATTCCACCA TTGTGA TTG TTCCTGCCCC ACCTTGACTG AGGGArrTAAC CTTGTGAAAT TCCTTCCCCT GGCTCAGAAG CTCCCCGACT GAGTACCTTG TGACCCCCAC CCCTGCCCAC AAGTGAAAAA CCCCC'TrGA CTGTAATITTT CCACTACCCA CCCAAATCCT ATAAAACAGC CTCACCCCTA TCTCCCT7CG CTGACTCTCT TTTCAGACTC AACCTGCCTG CACCTAGGTG ATrCAAAAGC TL17ATTGCTC ACACAAAGCC TGTTGGTGG TCTCTTCACA CAGACCATGT GACATI17GGT GCCGTAACTC AGATCGGGGA 35 ACCTCCCTTG GGAGATCAGT CCCCTGTCAT CCTGCTC'I= GCTCCATGAG AAAGATCCAC CTATGACCTC TGGTCCTCAG ACCAACCAGC CCAAGGAACA TCTCACCAAT TrTAAATTGG GTAAGTGGCC TCIT1TACT CTCTTCTCCA GCCTCTCTCA CTATCCCTCA ACATC'ITCT CCT=CAATC TTGGCACCAC GCTTCAATCT CTCCCTTCCC TTAATTTCAG TrlCCTCTT TrCTGGTAG AGACAGAGGA AACGTGTFTCT ATCTGTGAAC CCAAAACTCC AGCACTGGTC ATGGACTTGG AAAGACAGTC TTCCCFrGAT GTTTAATCAC TGCAGGGATG 40 CCTGCCTGAT TATTCACCCA CATTTCAGAG CTGTCTGATC ACTGCAGGGA CGCCTGCCTG GATCCTTCAC CTTAGTGGCA AGTACCACTT TGCCTGGGTG GCAAGCACCA CCTCTCCTGG GGGGCAAGCA CCACCTCTCC TGGGGGGCAA GTACCCCCCA ACCCCTTCTC TCCATGTCTC CACCCTCTCT TCTCTGGGCT TGCCTCCTTC ACTATGGGCC ACCTTCCACC CTCCATTCCT CCCTITCTC CCTTAGCCTG TGTTCTCAAG AACTTAAAAC CTCTTCAACT CACGTCTGAC CTAAAACCTA AATGCCTTAC TTTCTTCTGC AATACCGCTT GACCCCAATA 45 CAAACTCAAC AATGG'ITCCA AATAGCCTGA AAACGGCACT TTCAATTTCT CCATCCCACA AGATCTAAAT AA'rrTrGTC GTAAAATGGA CAAATGGTCT GAGGTGCCTG ACATCTGGGC AT7CTTITAC ACGTCGGTCC CTCCCTAGTC TCTGTTCCCA ATGCAACTCA TCCCAAATCC TCCTCT=C CCTCCTGCCT GTCCCCTCAG TCCCAACCCC AAGTGTCGCT GAGTCTTTCC AATC'rrCCTr 1TCTACTGAC CCATCTGACC TCTCCCCTCT TCCCCAGACT GCTCCTCCTC AGGTCGCTCC CCGCCAGGCT GAATCAGGCT CCAATC'rrC CTCAGCGTCC 50 GCTCCTCCAC CCTATAATCC TTCTATCACC TCCCCTCCTC ACACCTGGTC CAGCTTACAG 'TrTCArrCTG TGACTAGCCC TCCCCCACCT GCCCAACAAT TTCCTCTTAA AGAGGTGGCT GGAGCTAAAG GCATAGTCAA GGTTAATGCT CCTTI'TTC'IT TATCCAACCT CTCCCATCTC AG'ITAGTATI' TAGGCTITI1 TTrCATCAAAT ATGAATACCT AGCCCACTCC ATGGCTCATT TGGCAGCAAC TCCTAGACAT TTTACAGCCT TGGACCCAGA GGGGCCAGAA GGTCATC'ITA TTCTCAATAT GCA=ITT ACCCAATCCA CTCCCAACAT TAGAAAAAGC 55 TCCAAAAGTI' AGACTCCGGC CCTCAAACCC CACAACAGGA CTTAATTAAC C'FrGCCTrCA AAGCGTACAA TAATAGAGTA GAGGCAGCCA AGTAGCAACA TA T7CTGAG TTGCAATL'CC TTGCCTCCAC TGTGAGAGAA ACCCCAGCCA CATCTCCAGT ACACAAGAAC TTCAAAATGC CTAAGCCACA GTGGTCAAGC ATTfCCTACAG GACCTCCTCC ATCAGGATCT TGCT7CAAGT GCCAGAAATC TGGCCACTGG GCCAAGGAAT GCCCTCAGCC TGGGATTCCT CCTAAGCCAT GTTfCCATCTG TGTGGGACCC CACTGGAAAT CGGACTGTCC AACTTGCCCA 60 GCACCCACTC CCAGAGCCCC TGGAACTCTG GCCCAAGGCT CTCTGACTGA CTCCrTCCCA GATCT[TTG GCTTAGTGGC TGAAGACTGA TGCTGCCTGA TCGCCTCAGA AGCCTCCTGG ACCATCACAG ATGC'II'GG TAACTCTrAC AGTGGAGGGT AAGTCCGTCC CCTTCrrAAT CAATGCAGAG GCTACCCACT CCACATTACC TTCTCT'TCAA GGTCCTGTT CCCTTGTCTT CATAAATGTT1 GTGGGTAT17G ATGGCCAGGC TTCTAAACCC C'ITAAAACTC CCCAACTCTG GTGCCGATI1 AAACAACATT CT=h1ATACA CTTCTP1TA GTTATCCCCA 65 CCTGCCCAGT TCCCTTAT'rA GGCTGAGACA 1TITAACCAA ATTA TI'GCT TCCCTGACTA rrCCTGGACT ACAGCCACAT CTCATTGCTG cCCrrC'rCC CAACCCAAAA GTGGCAACTC CTTFGCCACT TCCTCTCATA WO 00/62736 PCT/USOO/08020 150 TCCCCCTACC TrAACCCACA GGTATGGGAC ACCTCTACTC CCTCCCTGGC AACAAATCAC ACCCTCATrA CTATCCCATr AAAACCTAAT CACCCTACC TGGGTCAACG CCAGTATCCC ATCCCACAAC AGGCTITAAA GGGA'ITAAAG CCTG'ITATCA CTTGCCTGTT ACAACATGTC CTITAAAGC CTGTAAACTC TCCTTACAAT TCCCCCAT TACCTGTCCA AAAACTGGAC ATGCCT-FACA GGTTAG17CA GGATCTGTGC C'ITATCAACC 5 AAATTGTC'IT GCCTATCCAC GCCATGGTGC CAAACCCATA TACTCTCCTA TCCTCAATAC CTCCCTCCAA AACCCCTCCA TAACCCTTfAT TCTGT7CTGG ATCrCAAAAC ATG=CIC7 TACTAYrCAT TTGCACCC'rr CATCCCAGCC TCTCTTCACT TTCACTTGGA CTGACCCTGA CACCCATCAG CCTCAGCAAC TTACCTGGGC TGTACTGCCG CAAGGC'ITCA TGGACAGCCC CCATTACCTC AGTCAACCCA AATh7CTTCT TCATCCATrA CCTATCCAGG CATAGTrCTT CATGAAAACA CACGTGCTCT CCCTGCTGAT CATGTCCAGC TAATCTCCCC 10 AACCCCAGGA CTGGCAAATT1 GAC'ITTACTC ACATGCCCCA AATCAGGACA CTAAAGTACC TCTTGGTCTG GGTAGACACT TrCACTGGAT AGGTAGATGC C'ITTCCCACA GGGCCTAAGA AGGCCACCGT GGTCA'TrTCT TCCCTTCTGT CAGACATAAT TCCTTGG'IM GGCCTTCCCA CCTCTATACA GTCTGATAAT GGACAAGCCT TTACTAGTCA AAGCACGCAA GCAGTTTCTC AGGCTCTTGG TATrCAGTGA AACC'VrCATA CCCCTTACCG TCCTCAATCC TrAGGAAAGG TAGAACTGAT TAATGGTCTT TTAAAAACAC ACCTCACCAA GCTCAGCCTC 15 CAACTTAAAA AGGACTGGAC AGTAC'I1TTA CCACTT1GCCA TTCTCAGAAT TCGGGCCTGT CCTCGAAATG CTACAAGGTA CAGCCCAT' AAGAYI'CTGT ATGGACGCTC C~fT=ATrA GGCCCCAGTC TCAYTCCAGA CACCAGCCCA ACT]rGAACTG TGCCCCAAAA ACTI7GTCATC CCTACAATCT TCTGTCTAGT CATACTCCTA TTCACCA'rrC TCAACTACT7 GTAAATGCCC TGCCCTI= TACAGTGCTG ANIrfATACTT TI'CCTCCAAA CCATCATAAC TGATATCTCC TGGTTrACC TCAAACCGCC ACCC=AAGT CTCTCTTAAA GTGGATAGAA 20 GATCTTCAGT GACAAGGTAC ACTCCAATAC 'TrCACCCTA ATAAAGCCCT ATTCTT-ACT =~ATATfCA CTC'11ATTCT TGTTCCCATT CTTATGCCAC TCTCTACCTC TCCCCAGCTA TCTCCACCAC ACTATCAATC TCACTCACTC TCTCCTAGCC A=IICTAATC CTFCTIT7AAC AAACAAT7GC TGGC'ITTACA ATrrrCTCrr CCTCCAAAAT CACCGAGTCC TCAATI1TACT CAGTGCTAAA AAAGGGGACT CTGCATAT IT TTAAATGAAG AGTG TrGYI7 'TACCTAAAT CAATCTGGCC TGGTATATGA CAACATAAAA AAAACTCAAG GATAGAGCCA 25 AAAACCTTGC CAACCAAGCA AGTAATTATG CTGAACCCCC TTGGGCACTC TAATTAGATG TCCTGGGTTC TCCCGArTCT TAATCCTTA ATACCTG'IT TTCTCCTI'CT CTTrATGCAGA CCTI'GTGTCT TCCATTrAGT TT1CTCAATTC ATACAAAACC GTATCCAGGC CATCACCAAT CATI7CTATAC GACAAATG H' 'TAAGGGAGG AGACCACCCC TCATATTGTC TI'ATGCCCAA TITCTGCCTC CAAAGAAAGA AGTAAAAATG AAAAGGCAGA AATGAAATCC ACAGGCAGAC AGCCTGATGC CACACCCTGG GCCTGGTGGT TAAGATCAAC CCCTGACCTA 30 ATCAGTTATG TTATCTATAG ATTACAGACA TTGTATGGAA AAGCACTGTG AAAATCCCTG TCTTGPIFCTG TTCCTCTAAT TACCAGTACA CGCAGCCCCT AGTCATGTAC CCCCTGCTTrG CTCCCCCTGC TTGCTCAATC AGTCATGACC CTCTCACGCA GACCCCCT7A GAGTTGTAAG CCCTTAAGAG GAAAAGGAAT TGTTCACTCG GAGAGCTCGG TTGAGAC ATGAGTCTTG CCAATGCTCC CAGCTGAATA AAGCCCTTCC TTCTTTAACT CAGTGTCTGA GGGGTTI'GT CTGTGTCTFG TCCTGCTACA G'I=CATCTA ACAACCCCAT AATATCACCC 35 CTTACCACAA AATCTCCTT1 CAGCTTAATC TCTCCCACTC TAGGTTCTCA CGCCACCCCT AATCCTGCTC GAAGCAGCCC TGAGAAACAT CGCCCGTTAT CTCTCCACAC CACCCCCAAA AAT1TCACT GCCCCAACAC TTTACCACTA 'TrTCGTTTA 1T1TCTTAT TAATATAAGA AGATAGAAAT GTCAGGCCTC TGAGCCCAAG CCTGCACGTA TACATCCACA TGGCCTGAAG CAAGTGAAGA ATCACAAAAG AAGTGAAAAT GGCTGGTTCC TGCCTTAACT GATGATATI'C CACCATTGTG AT7GTTCCT GCGCCACCTI' GACTGAGGGA TTAACCTTGT 40 GAAATTCCTT CCCCTGGCTC AGAAGCTCCC CCACTGAGCA CCTT1GTGACC CCCACCCCTA CCCACAAGTG AAAAACCCCC M~GACTGTA ATMTCCACT ACCCACCCAA ATCCTATAAA ACAGCCCCAC CCCATCTCCC TTGCTGACT CTATI1TGG ACTCAGCCCA CCTGCACCCA GGTGATTCAA AAGC'ITCATI' GCTCACACAA AGCCTGTTG GTGGTCTCTT CACACCGACA CGCGTGATAA TTAT7ATAT~r AC'TTfAACT AAAACCC T' CAGAGTCTCG CAGGGAAGGC TGTATATATC TCATAAAATG TTGGGGCCCA CTGGATCAGA CAAGGCCACA 45 AAGGCCAAAG GGAAGTAAAG ATCTCATTAT 'ITCTCCTAAT AATrCCCTG TCC=~GTCA TAAATGGTGG GTAGGCTG'Yr ATGGTGATGG CAGATT7CT 'ITCCATAAAA TGTCCATAAT AGGACA'1G AACAGAAGGG AAAAATCAAA TlGCTGAAGT TGAAAGAGGG CAATGCAAAG AACTITGGAG AAAGAACTGT ACAGAGAAGT CAACTGGCAG ATGGGAGGAA GYTrAAGGGG AAAAATATAG ATGTCTAAAG AATACNTA TT1CATTrCC ACAGTGCAAT TTGGACAAGA AGCCTCTrC TTGCTCT= CTATI'CTCAT TAAATCATTA GAGCTCAAGC 50 AATCCTTCTG CCTCAGCTTC CCGACTAGCT AGGACTACAG GTATGTGCTA CTATGCCCAG CTAATVTr AAAAATTAGA TTAA1TTrG GTGAACTATT TCTGTAGGAA ACTACAATAA TACAGCCCAG GCACATTGAT CTTGGGTGAA CAAATCAGAA GGAATGAATA ATrCTGTGTT CCTGGGACTC TGACAATrC ATGAACTTGG TACTCTGAGT AAAGCATAGG AGGAGTTATI? TCATAAAATG TGGAGCACAA TCATGTGACA AAGATAATGG GATCCCCATT TCATAAATAA ATCTGAAGT17 CAGAGAGAGT AACAACTGGC CAGGGTCACA TCACGGAGAC 55 AGAGGCAGGG TTCCCACTGA TGCCTCTGAC TCCCTGTCCC AGGCCCTTCC TCCTCCCGCA AGCAGAAGTG CAGGGGGCAG AGCTGACCCT GTGCAGTGAA AATCTGAGGG CTGAG'PrCCT A ITGGAACAC AAGTGAAAGA M ~CCTGGCT TCTAATCTCA GGATAAGGAC TCAGAGCTCC ATCTGTTCCA GCC I17AGGAT AAGAACCAGA ATCTTACACC ATGAAAGCAT GAAAGGTAAG ATTTGAGTGA GGAAAAAAAA AAAAAAAGTC TGTGTMCAG A'I1CAGL17CA CAAAGCAG117 TCATACTrAA GGTACCATCA CAATAACCCT GTGGGGTAAG CAAGGCAAAT 60 TTCATTCTTG YT7ATGGGC ATAGGAAGTA AGTCTCAGGG AGGTT1AAGAC CAAGGTTTCT GGAGAATTT ATATTATGAA TCTrGATTrA TGGGATTACT AflATGTAAT TCCTAAGATC ATATAGGAAT CCTAGAGCT7 GAATATAGAA CTTATITP AAATCTATAT ACATCATAAT TACAAGGAGT AGTGTCCATT TGGGTI'CCTT GGCCCTGATG TG'ITAGTGGA ATAAACATFT TTGTCAGGGT TGCCATGTGT GTCTGTGCAC GTGTGCACTG TACACCTCCA GGGGATGTAC CCTAAACCAC ATGAATGTGA TTTGCACATC CAAGA'ITrAC AGTGTACTAT 65 AGGGAGAATC TITT1GCAACA GC'IT1GCTA TAATACAGAA TCTGAGATGT CTrrGAGAAA GAAAAGTGTA ATCATTACCA AAAAATTATT CTCATAATGT GTGCAAAT'1T GTATGAAATC TATATTGGCC ATGGGACAAG WO 00/62736 PCT/USOO/08020 151 GAGGTAT=C CAGCTAGCYI7 CTGAAAGGGC TCTATTCTCT CATAAGAATF CAGCTGTTGA CA'FrAGGTGA TATCTGCCCA GGTCATCAGA TOCCATAGAG AAAGAGGGTr TGCTGAAACT TATATCAGCA GTGCACTGTA TGCTCTTrCT GArA TrG AACATTCATI' TATI'GAGTGT CAAGTAATGC ACTAGATACT CCAGGGATCT GACACAAACT CTGCCCTGAA GGAGCATGTA ATCTCACTGG GGAGAAAACA AAACATATGA TAATCAAA 5 ATAACAAACT AGGCAAACTA G FrAACAcrr AAAAAGCAGG C1TYCAA ATGCAAAATT GCATGTrACA GGGTAACCTT TCAGTAAGAA GCCAGGAAGA GGAGCTCATC ATGGGTTGGA TTAGTAAAGG ACTAGTTATA AAAGAAGTGG TGGGGTTGAG GGAGGCCTGA GATGAAA'rr AAAGAATATG TAGAATCTAG GTAAGTGGAT AAAAGGTCTG GGGGCAGGGG AAAGGAGAGC ATI11CAflGT GAATCAAGGA A M CTCCAC CTGTITAAC TCTrCCATAT GACATCAAAG AGATGTCACT TGCAGCTAGC ATrCAGTGA TGT1TCTrA CTAATAATAT 10 CGTGATAAAA GAAACATTGA CTATAAGAAA TAGGAATGGG TCTCATAAAA GGAAACAGCA AAACCCCCAA ACTAAAAAAC AGCGCAGGCT ATCTCTCT TCTCTCC'rIT TGCTrGGCAC TCATGAGATG CTAGGTGTGG AAGTCAGCCA ACTGAAAAAG AGAGGTGGCT GAAGAAGGTG GGGAGGCTGA AGCCAGT7AA ATAGGATGGT CCAATTCACA GACGGCGAGG CTACAGTGCA AATAGGACTC M~CAACTrG AGCAGGACCC CATTACFTCA CTGGAGTTrAG AAAGAAAGGA GAGCGTAGAC TITIGAACT Tr1CTATAAGA GTGTACCTCC ACAGTATACA 15 GAAGACGACG TGAAAT-ffGA TCTGCAAGAA AACTGAGTCC ATATTCACAT ATGTATCAAA 'TrGCACTTC A'TrAGAAGT GTCTGTCATC AAGTACAGCA CTGAATTGAA ACTGAAAACA AGAGTCAAGA AAGAGCAAAG TCAGCCATCT TTATATTCCA CATGAATCCT TrCCC'rrAT GGTCTTATTT G'ITTCTCCTC AGAAAAGACA AAAAGCTGAG CTGTATAAAC ACCTGTGGGC TGGGGGTTGA GGGATAAATG AGGGGCGAAA TGGAAGCTGA AGGAACTGTT GGTCAGGTAG AAATCTTCCC AGATGCACTG AAGGAAACAC ACTrCATGTT TGACGTAGGA 20 GGTGCCACCA CACAAAACGT TTCATGGAAG GAMTAAAGG ATCTCATGAT =I~AGTA'rr CCAAGANTT TCMIICACCA AGGGCGAT'rr AATATGGGTC AYrCATACTG AAAGAAAAAC AAAAGATAAT AAGAGTTAA AAATTGCAAA AC'rrGGAGTG TTAGTAGTAA AGGTAAATAT TCATTAGAGA TGAGAAGAGG AGCAAGGAAA TGCTTTCAGC TGGAAATCTC AGACAAGAGG CCAGGC'ITrA GGAACCTCTG AAGATGAACA AATGTAAGCA AACCCTAGTA GCAGCACTTC TCAGA=IIC ATGTGCTTAC CACTCAGAGA TGGTGTTAAA ATGCAGACTC 25 TGATTCAGTA GGTCTGAGTG GAGCCTGAGA TT1CTGCACCC CTAACAAGCT CTTTAGTGAT GC'ITATGCCA CTGGCGCACA GACCCCACTT GGAGAAA'ITr TTGTGGTGCA TACGGTCTTT7 GTCTCCAGAT CTAATGAGTC TGAAGGACAG TGTAGATFGA TITITAAAT TrATGTITAT TTAAMTAA ITrAATTTAA TTrATTTATT TA'TrTA'Tr TGAGATGGAG TCTCACTCTG TTGCCCAGTC CGGAGTGCAG TGGCACGGAG GCAGCTCATG CAACCACGGC CTCCTGGG IT CAAGCGATTC TrCCGCCTCA AGTFCCTGAG TAGCTGGGAA TACAGGCACG 30 TGCCAGCACA CCCAGCTAAT TITTGTATITf TTAGTAGAGA TGGGGTTTCA CCACATTGGC CAAGCTAATC TCAAACTCCT GACCTCATGA TCCACCTGCC ACGGCCTCCG AAAGTGCTGG GATTACAGGC GTGAGCCACC GAGCCCAGCT GTAGATTGAT 'LTTGAGCAGT GGAAAGTCAA GGAATTAGAA GGCATGC317A AATGGAAAGT GAAATTGGAG AAAATAAA CTCATGAAAT AGTGGTGGTI' ATAAACTCGT GATAAATTAT ATCCTGGGAT ATAATAAT GAGATGGTAA CACAn7~AGT TTAAAGAAAT AAGTGACACT TITITGTGT GACACAACTG 35 TCTT1A'TT= GGAAAGGACA AGGAGAGAAT GAAATATGGT ATGTC'1CAC AGCACCTTTC AAAGGGAGAA CCAGATTCTG AGGAGCTGGT CTCATGATGA ACTGTCAGGG TAAACCACAG TTCAGCAGCT GCAAATGTGC T7GCCAAAAT AGAGACAAAA AAATG=~CT GAAAACAAAA TTrCACATAT GCCCTCCTCT GAGG31?GGCA TCATATCTTC CTGTGTATCT TGGGTGTAGC TT1CTATCCTG CCAGAATTTA GACAGTAGAA ACCAAATGAG GTGATAAACA GAGTCATITI GCAGAAGAGT CAAAATAACC CAGCAAGAAA TGAAACCACA AATGCCCAAG 40 GAGTCATTCA T-FCACCATTC AAAAGCTAAT AGAAATGAAC ACAAACTACT ATGAAAATTC ACCCAAGAAC TI'AAAAAAAA AAAAAAAGGC TCATGGTGTT TAGTGTGATA GTATTCATI TACCTrTGAC T[TGTTCTAAA AACACACCAT ACTrCTACCC CACCCTTCCT CAGTGCCGTC ACACAATGGT TTCAGTGTGA AAAAAAAAAC CACGT'rACTG GAAAAGGAGG GTGCCTGGGA C'ITGCCACTC TAAGCTGGTA GTCAAGGGTC TTGAGTTCTA AAAGCATACG CGTTAAGAGC ATGATTCCTG GATCCAAATG AGTATGGATC TCAGCATrGC CATTTATTGT 45 GACCTCAGGC TATYTAT CTCTGTGCCT GMTCMIAT CAGTAATGAA GATGTTCATA GACCCPITCTC CCACAGACYT AAAGGCATAT TTCATGATrT AAGACATGTA AACCATTCAT AACAGTATAC AACATGGAAT TAATATTTGA TAAAGG'ITTA TGATTAYIGT AACTAACTCT GTCAC117GCT CAAGGCCTAT AGAAAACTTA CTrAA'ITAGT TCAACTACAA AAAGAGTTTG AATGTGATAT CCACCAAGAT CATATI1CAGA CCTAGAATTC TGTGATrCT'r ATGAATT1AAT ACAGCCTTGG TCAATAAATG AGAGCTGGGC AAATAATTCT TC'ITTGCTAG 50 GCC'LTTCTAG ACCATCTGGT GAAGCA'ITCA AGACTTATGT TATfGGGGCC AGCCTTCCTT TCCAACTI1CA ACTCCACAAC TCCTCAATAA GCCATGGGCT CAAGAAAGT7 CTGCTCAGTG GCCCCTGAAA AATGCTrCA TAGTCTCACT ACCATACCAC TGCTI1ACACA ATFTCCTTCC TACAGACTGC C'rrCCmTCC TGCTTTTCTC CATATACCTA AATCCTATCT ATTCTTCATA AGCAACCTTC =ATAACAT 'JTCTATAAC CACCAAGCCA AATGACCFI17 TCCTTCTTAA ATATAGCACC CATTGGCCAT TACCATGCTC TGCCTTGTAT mT=CTGATr 55 TITTrC TATATFCCTG TCTTAACTCC CCAGCTAGGT AATAATIT7C CTGAAATCAG GGACCAGGCT GACTCCTCTT GCTGTCTCAA GAAAGCTTAG CAG I= CCAA CACAAAAATG rITCAATAAAC AACTATTAAT TGACTGATI'A TAAAAAATCA GTGAACCATT AAAC'ITAATA TAGCAATTTG C'rTAGCATGG TAA F[AGCTT TTGCTAATA 'I-CTTCCAGC CAGTCTCTCC TCCTGTGCCT CAAGGACATC TI7AAAAAAAA AAAATCTAGT TGATCTGCTI' CCATCTAGTG GCAATTAAAA CAGGTGGTTC CGGTAGCCAG AAAACAGCTC TGGGTAGATT 60 GTGCCAGAAA ATACTTTCAC TCAGTAGGTG CGAGTTTGAA AGAAATCTTC ACATCTGTGG GTrCCTGCC ACAGACATAG GGAGACCAGC CCAGAGAAAG AAGCC'ITCC TCACTAGACT CCATTTGCAC TAGTAAAGAG AAGACAGAGT AATTAAAAAG AATAAAAAGA ACCTCCACTG ATCGTACATC CTCATCCAGT TACCCCTGCC CCACTI1CTCC TTCACAGCCA AACA'TM1AA AAGAGATGAC TGCTIGTrCT GTCTCTACTT TCTCATCCTC AGTAATGCTC AATGCTTGGC CGTCTGACCT CTGTCTTGAT GTCTGCACTG CAAATAGTCT CCCCACTGAC 65 ACCCTTGTTG CATCCAGGGG ATACITACTG GTTCTCTTGG CAATG'TrTGA AACCGTTCCC CTTCTTTGT 'rTCCTTGGCA TTCATFACCC CACACTCTT CTCCTCTTCC TrCTCCCTGC CTGGCAACAT CTTrCA'l= WO 00/62736 12PCT/US00/08020 CTC'TrCCCT TAGGTGACTT A'PTAGATAAT GATGTTCCTC TGGCTCCCAT ACTCTCTCCC AGGTCCTCfl CCAT7CTTFAA AGCACTCACA CCCTCCCTGG ATGATAGTAC CCACTCCTGA GATGGCAGTT ACCTCCTGAA ATGTGAGGGA CCCAAATCCA CTTCTCCTGC CATAGCCTCT GTGC T7GGA TAGGTCCAAT GAGCCACAGT GAATGATGTG CATACACCCA AAGCTCAGTA CAAAACTGAA CCCATGATCT 'ITACCTCCAA AACCTCTCAT 5 TCTTTTATGT TCCCTrCTCA GAAGTAAACA GGACTACCAT CCGCCAGTITT CCAGGTGAGA AAGATGATAA TGA~rTT CTCTCTCACT TTTAGCCAAT TAACAGACAC ATTCAGTTAA TATCACCTCC TCrrMArCA TGAACCCATr CTTACTACTA GTFTCCCTAGA CAGGCGCCAT CGGTnTAAT CTAATAACTG CAAATGCCTC CAAAACAAGT CTCTTTGAAT CCAGGCTCAC CTGTCTCCCA CACTTGCCAT ACTGCTCTGC AGGGTGACCT TATAAGATGC CAGAGGTAAG GCTACTCACT G'TrAAACCC C'ITAGTGAT ATCCCAAAAG ACCTCAAGAT 10 AAAGCCCATA TCACATGGCT TATACATIAG TITATGATCT GG=TCTGGT GCCTCA'Ir TCCCCAcnrT 'FrCC'=GCA TTCTAAGCAA TGGCCCATAC TAAGTTTGTG ATTGGTAGGA TGGTTGCCCA AACCAGCATC CAATCC=TC AGAAATCATC TCACTI1CATT TCTAGCAMT TAAAGGAAGC TCAGTTGTCC AGCTGGGTAC TGAATATGTC ACCAAAGTCC TCCT1'CATA GMTATITA CTTAAACTCT CCTI'CCTAAA ATrCCAGAGC AAGTCACTAA ACCCTAGATA CTGAGAAATA TIT~CCATC FrCATrCTG CCAGGTGGGC CATCAAC'TT 15 CACATGTCTG CATCTCCTCC CACTGTGCTA 1TrCTCCAGT AGAAGAAATT TGAGCI17CAA GACCAAACTG AAAAATACYI7 GCCTCCTTGG GGAAGCTGTA GGTAGAAT11C ATGCTCCCTA TC'TrCCCAC A'TrCTGAAG GACAATGCCT GTTAGAGCAA 'PTGAATGCAA ATAGTCAATTI GAATAAGCAT TTATTCA'rIT CTCAATAAGT GCTTGT'rCAA TTGAATKITT CTTAAATAAT ATATITAAGA ACAAGAAGAA CACACCACAA TGTTMAAC CCTCAGAAAA AATTCTGAGG TAATCAGAAA AATCTCCCT1T TACATAAACT GCCC'flTTCT AATAGGGATT 20 ACTTGTTCGT TCATTCATT1C ATTCAGCTCC ACTAGCACCA AAAAGCACAG CTCTGAAAGG AAGCTAGTAG ATTTATCACC TTATCTGGTC AMTGGATGA GGACCCCAGG TAAATAAACT ACTATGGGGT TAATGTGTCT AGCTAGAGCA GGAAGTAACT TAAGGAAGTA GAGAATGAAT CAGCAGATGT GGAAACTCCT CGCCACTAAT AAAACTTACC 'rrCTCT-rGGA 'ITTCTrGCCT GAAAATAGAA AATAGAGAAA AGGCArTAGC AAAAATTAGA CAATITAAAG TITrCAAGT AAGGGAGAAG GAAGACTCCC ACTCTCAAAA CTGTC=h~G AAGTATAT7A 25 GGTATGTT AGGTGGACCC TATCTGTGTC AAAGGAGAT1' TGAGGAACTG GC'TAATAAA CAGTGGTAGA CACTAATACA GAACAGACAT GTTGATGCAG ATGCCTCCTG AGGTTCCATT CCATTCTCCG TGCTACTCAA GAAGACAGAA TTGCTAAATT GCCTGGTGGC AAGACCCAAT ATGTCCATrC AAGTG1TTAT CCCTTCCCAA TCTGCCATCT CATCCTACCT GCAGATTCTT CCCTGAGGG ACAGCTGCTA ATACTGTAAA ACTATGTGCC ATTACAGCTC ACAGCATCAT CTCTATGAGA ATCCACAAGA GAATITCACT TTGGTCT[GT TGGTAGGAAT 30 TGTGCAGCCT CATCTGAGTA ACTAATGTGT =1TATCTTA CAAACACAAG GAATATCACA TGGYTCTCCT T~rGACTGGCT GTAAGGAAAC TCAGAGCTAG ATCTGAGACC CTCTCGTACC AAGTATATAA AAC ITTGTGA CATACATTTT TGTGCCATAA CTTCAACCTT GG FTCCAAAT GATTTTTGTA CCCTAAGTTT AAATTTGGCT TTC'rfr 'TTTrGTA CTCAATAAAA CATCAAGCTC A FIT'ATr GCGAAGAGCG AAACAACAAA GCTCCACAG CGTGGAAGGG GACCCGAGTG GGTFGCCCAA ATTGGCTrCT TITCTTACT T=AAYTAA 35 TFrAATTTG CTATACTGAA CACA IrGT ACTG I1CTCA CATTCT1TE GAAAAAAGCA GAATATAAAT AAGTAGATAA CTTAAAAAAA ACTC'=GAG CAGAAAGAAT CATI'GGGAG GCAATATATTf TCAGTGGCTG TAAAGTGGCA TTCTAGAATC ATCCTACCCA GGTGAAAGCC CTATITTGCC ACCTGTAGTG TAGTGTGTAT TTGAACAGCT ACTTC'IL CTAAACTACA A'TrCTrCAT CTGTfAAAGA GGCATAATAA TJ7GTATCATC CTCAT7GGGT TGATAAAATA AAATNTTCC AAGTA'IMAG YFCAGGTCCT AGCACGTAGA CAGTGrrGCA 40 TrACTG'TJT AATCC'ITTAA AGTATTAAAG ACTACTA'IM GAAATCTIT CTTCTAAAAT TCAGCCTGCT GATGACCAAG TGCACTTGAG CAGGGGGAAT CAAATCTGAA 1TAATTTCAG AY1'CTGGTTA GCTTCACATA AATATTT TFAGGGATGA TGAACCTAAC AGCAATAGAT GAGTAAGAAT CTGT~rCCTAC TGAGAGAGTT TCA'T=rGAA GAAAAAGGAA CTAAGGGGGC ATGTGTTCAG TrCATGCCC TGGTCTAACC CTGTGTGTTG GTTCTGGTGG GAAATrC'rrC CAACCGAGGA AAAAACCAGT TCACAAATCT GAAGACCAGT GATTAGAA 45 GATGTATCTG GACTGGAGTC TAATCTCTGA CTCTGGGTCC TGCTGATATG GTATTTGA GATITGGCCT AAAACATCAT TGCCCTGGTI7 TCCTTATTTA CCAAACAGGG CCAATGGTAG TGACTAATCA GAAAATGATA ATGCCTGGTG CACAAAATGT GTCTAGATGA GCCCATGCAC AAGGACACAT G=~CTGGAA CTGTTCCTA 'rrCCTTTCCT AAAAGAAAGG AGGGAAAGTC TCCATACTAA GACTACTAGG GCAGGGGACA AAGTGCTAGA GTCAGAAGAT TCATCTGAGG ACAGAAGAAT AGGGGTGAAG GCTCTAGTCA CTTCATFTGGC TACCATGCTC 50 TAAATAGTTA CCTGTGCCCT TITCTAACT ATTAGAACCC AAAAAGCCTA TAAATTCTCT CTCTCTCTCT CTCTCTCTCT GTGTATATAT ATACATATAC ACACACACAT AGACACACAC ACACACCTAA ACACACACAT AGAGAiTAT GACTITIAC =FTATCCTT GTAAATGCCA TTAACTATAT TTTGTCTTAG A TTAGCCTG GGAATGTAGC CATTATTTCT ACCA FTGCCT CCATAGGAAA AATACTCTTC ATGTTrTAAA GGACCAACCT ACAACTAAAA TC'1TTGGAAA GCAGAATCAT 'FrGTAAGrG GTGAAAATGG AAGATGITGT ITATAAATG 55 AAGACTrrf Tll-TIT1T =FGAGACA GGGCCTCACT CTGTTGTGGA GTGCAGTGGT GCTGTCATGG CTTrACTGCAG CCTTGACCTC CTGGGTTCAA GTGATCCTCC CACCTCAGTC TCCTGGGTAG CTGGGACTAC ATGTGCATGC TACCATGCCT GACTAATT 'TGTA'TI1 GTAGAGATGT GGTTTCGCCA TGTTGCCCAG GCTGGTCTTG AACTCGTGGG CTCAAGTAAT CCTCCTGCCT CAGCCTCCAA AAGTGCTGGG ATTFAGAGGTG ACAGCCAAGG TGCCTGGCCC ACAGATGAAG ACTATI17AAT GTTATCTrAA AGATACCCTA AGCTI7CCTAC 60 CAAGCCAGTG ATC TVFGGG GC'FrCTGnI7 TCTITGTTGG CATAACTGTA ACTAGCCTAA CTGCCCGYI'A TCTGTTTCCT G'1TTGCCCCA CACTGATTCC CACAGCAGTT 'TCAAGTrTAT CGGTTTGAGA TCTTGTACAG AAATGACTCC AAGGTAAAAA A TTAAAAAC AACCCCTCTA ATTI1AC CCTTGCTTAT AAAACAGCCT TAGCCAGCTA ACCCCTCACT ACATGCAAAT GAGMJGATT CTATTCTTr GA17CTACAA ACACTTATTA AAAGA FTLA GAATTCGGAA ATAAATAGCT TCCTTATTAA GGTGACTTAC AGCCCCAAAG TCCTTAAAAT 65 TATTrAGACA ATAGCCACCT TATCCCAGGG GGCAGTGTGT AATAACCCAC CCTGTTCTCT ATCCGTCAGT TCTGCCATCA TCGCCCAAGG TAGGAAGAAA GACAGGACAA CCGGGGTCAA GATTTGAAGT CTCAATGGAA WO 00/62736 PCT/USOO/08020 153 AGAATAATCA GTGGTTGGAG AAAACTGTCA TrrCTI r GCCTTAATGC AGTACTTGAT ACTTATACTT AGTACTGTAT AGTACTI7AGT ACTGTATAAT ACTATAAGAT AGTGAGATrC AATCAGCACA GAA'ITCTAA TAGCAAGGGC AGAGACATTT TAACTGCTCA GTGCTCTCAG GTTATACATA GCTAATGAAG TTC'ITGCATA TCAACAATCC CCACCCCCCT CACACAC'ITT GTCTTCTGG ATTGGTTAGA AAACTTACCT AGCGCCCACT 5 ATTCTCAAAT TFAAATGAAA GATAAGATCA GAGTGGCACG CAATTAGGGA CTGATAAATA ATATT1TTGT AATTGCCAGT GTAAATGGAC AGGGGGCAAC CTrACATAC CATATrCAGT GAACAGAATA CGTACTAACT AATI'TGATGG AAGGAAAATr AAAATGACAA TCAACTGAGC CCACAGAAAG GCAACACAGA GCAGTTGGTT AGCAATTGTT TCGAGATCAT CCCTGAACfl GAAACAGGTA TATCTTI TT~TT F[ TrGAGACAGA GTCTCACTCT GTCACCAGGC TGGAGTGCAA TGGTGCGGTC TCAGCTCACT GCAACCTCCG CCTCCCGGGT 10 TCAAGTGATT CTrCTGTCTC AGCCTCCCGA GTAGCTGGGA TTACAGGTGC CCGCCACCAC GCCTGGCTAA TI=GTATT LTTAGTAGAG ACAGGG ITC ACCATGTTGG CCAGGCTGGT CTTGAACTGC TGAGCTCATG ATCCGCCCGC CTCGGCCTCC CAAAGTGCTG GGATTACAGG CATGAGCCAC CACACCTGGC CAAAACAGGT ATATCTTAAA AGCTGCCCAA TGTCCATGAA TGTTACAGCC TTGAATGGTr CTTCCAGGTG AG LTTGGCCA AATGTGGCAC CATACACCCA AGGCCTGCTG CAGGCTAGTG GG'ITGCTCAC ACTTTAAAGC TGAGACACAC 15 TCATGCCTTA AGGTAAAGGG AGTGATAATC TGGGCAGCAG ATGTTAACTT CTCAAGGCAG TCCTCCTTCT C=fCCTCT CCAGTGACGG ATGGTrGGAA AGCATATATG GTGCA'TrrGG TFAGAGCTGT GGCCTTGGTG AATAGATACT TGGGAGAATA CATGGGAAT TCTCCCAGGG TrAATGCAAT GCCCATGTGT TGGGAACCAG GTGACTCTTFG AAGAGGTCAG GTAT~GGGA GCAGTGCCTr GAAACCT~rAG TGGACATTAG ACCCACTTFCC TAGTGGAATT GTAGCATTFGA AATCCAAGGC ATGTAGGCTC TTAGAGGACA GAGATAGTGT GTCA TTTT 20 CAGAATTAAT TAAGAGCAGG CCAGGCGTGG TGGCTCACAC CTGTAATCCA AGCCCTrGG GAGGCCAAGG CAGGCAGATC ACGAGGTCAG GAGATCGAGA CCACTCTGGC TAACACAGTG AAACCCCGTG TCTACTAAAA ATACAAAAAA TrAGCTGGGC ATGGTGGCAC GCTCCTGTAG TCCCAGCTAC TTGGGAGGCT GAGGTGGGAG AATAGCTTGA ACCCAGAAGG CGGAGGTTGC AGTGAGCTGA AATTGCACCA CTGCACTCTA GCCTGGTGAC AGAGTGAGGC TCTGTCTCAA AAAAAAAAAA GTAI7AAAGA ArrACATAAG AGCAAAGAAC CATTAGAATA 25 TCTCACTTAG TTGTTATCAG CCTAGCAAGC TGC=TGAAG GTAATAGACA 'TT=AAAAG 'ITATCAGAT GAAAAGCGAA AATCAGCCAA CCTGTI=AA TGAAGGTGTG TCCTGGGCTG ATACATGT CTCCAGGGAC TGATGGCTCT AGAATGTAAA GCT-FGGCATC CTGMTGTGT TGAATCTATC ACA'LTTAATr TCCTGTGGGT TrCTITI T rC'rT=C ACTTAAAGT TGTGTrCTTT TCATGTGAAG TAAACTCAC ATACCTITJ TTAATCTCCT TGCCAGCCAA ATGATAAATG CCAACCCAGA GAATGCAGTA ACCATGACTG CCACTGGAAT 30 GAAGAGGGGG TTATAATCAC CCTCC =TAAT CA FTGAGAAA CTMTGTCCA ATTCTGAAAG AGAAATCAGT AAGGCACATA GCATGAGACC ACCAGCATTFA TTTCCT~rAGT CTATCTCATG ATATTTGACT TTTTrCCTCC TTACATCTCC CAGTAGTAGC CCATT7GATG CCAT1T7GACA GATGAGGAAA CTGGCATGGG AAGGCCCCTG ATGAGTCTAC AGCATAGGCA AAGACTGGAC CAGCCTTGCT AGTCTAATGC CTACAGAATC TCAATGCCCA GA'ITTGTGGT TCATAGAGTT CCTGAAAATG CACCTAAAAA TGTT'GGCAAG AATGGTCATC GTrGTA'LMA 35 GCTCCATGGA C'ITGTrCAAT GACTGGAACT CTGAAACACA GAGAAGAGCT AAAAGCCTAA TACAACTTCA GGAAAAATAA AAGCCAATGA TCTGAACTGG ATAATrCACC AGTCAAAGGA AATCAT7AAT GC'T=ACTr TAAAGCAGTJ7 GTGCAAAAAT AAGCACT7GA T-T=ACATG CCAAGGACCT GCACTAATT CTITCCAATG CAGTAGTTAC CACTTCCCTC TAC= CCTTC ACGAATAAGT AAAAGGGCAT G'IMAGAGAT ACTC'IGTAA GTGTAAACTA AG'ITCAT1'TG GGAGCCTCTA 'TrTGAAAATA CTGGTATAAA AAAAAATCTG TCTCCTGATA 40 CTAACATTTG AAGGAATCTA CTITTTACA TA'rrGGCAGA GGGTCTGATT CTATCCTFAG TTC FTCCCAT TACTrIrGATG AACCTTrCA AGGTGAMG ATCCCCACAC CCAAATATAT GAITGAGAGA AGGCTCAAGT TCCCAGGAGC TCCAGACAGA AGGTACCTGT TGGCTTGATG AAGATGAGGA GGAAATGAAC ACTAGCTAGG CCTITAAAGGG AAATGTCTCT GATAGGCCTA ATACACAGTC CTCTGCTAAA GGCCTCCCTG CCTCTCTCTG CTCATCCACT CTACTCCCTG GCCCTGGGCA CGCAGCACAC AGAGATCAGC ATJITCTGACA GCTI7CTGTAG 45 ATCCTACCAT T7AAAGACTT TTGTCATCCA TGCAGATAGT CTCAGGAGCA GACACAGGTA GCTA'FrCTr CACATGCTAG CTTAACATGC A'TTGC'TA GCACCTATTG CCAGGCACTG TGTCAGGTGG AGGGTATACA AAGATGAACA AGACATGATT CTTCTCATAT ACAGATAGAT ITTGGAGGCA TTAGC'ITAGT GATGAYTCAG GAGTATCCAT TA'FrTGGGGA AGTAGGTGGT CATTAGTGAC CTTTrACAGG CA'I=CAATG GGCTAACAGA GATGTT1AGAT TGTAGTGGAA TAGAAGAATG GGTAAAAAGT AAATCAGTGA GTTCAGA'TrT TAGGAGTT~AA 50 GATGGCAAGA GGTGAGAACA AAAAAAGGAA ATGATTGTCA TTAAAGGAGG AGGAAAGACC AGCCAAAGAT TTTACAGTGA GTTAAGCATA CAAATTTATT TCTAGGCCAC ATATTCTTAG CAAAACAACA TGTAAATGTT TATGTATGTC TICCTCATA TCTGCTCATC CATCAGCTCC ATCGTTAAGA 'ITTCAG ITIT CCAGGACAAA CTTACTCACT TTGACATATr GGACTAGGAT TTGACCAGAT TCCAGATGAT TCACAAATGG TrfrC'rrCTT CCCAATTAAC TCAGTTCCTT1 CTGAGCAGAT GAAGGTACAT GCAGAGGTAA AGCTGAAGCT GGCCAGGGGA 55 TGGCTACAGT TCATGATCCC CAAATCTGGT GCTGATAGAG GCTCACACTG AATCAC VrCA ATGAAAAAGA AAAAAAAAAA AAAGACAAAA CAGTA FITCT GAGTAGAGAC CCTCCCTTGA GCAAAGGAT-f TITAGCCAAA GCTGCCTGAC TACATTACTr GTGATATTGC TTCCAGGCT? TAT=1CTrG AGAATGATGG TGGGTGGTGA ATGAGAGATG AAGGCAAGGA AGCATTGAAA GCTGTGGGGA GAGGAGTAGC TACTCCAGGC TGCTGCCCTA GCTAAGGTGA CCCTCCCC11 CTGCTGGAAG TACCATGCCA TATGGCCTCT GCATCAAGGG CTCTITATGGG 60 ATATTCTCAG AGAATCTCTG CCG'ITTCATC TGTTCTGATA TCTACCCAAG CATITGAAA AACATCCCAA 'TCACTGAAG CAAGTCCAAC TTCCGTAAAT TCCAGTAGGT GGGTTGACAG TIMATAA11' TCAATAAGGG A TM1GATAG CACTTCTAAG AATFTAAACTA CTTAAACTAA TGCATCAGGA GCATACTrGT AGAAAAGTTA ACCAAAACTT CGTAAG FTCA GATGACATTG GTIT~CTCCC ATATGGAGAT AAGGTTGGCA GTTAAAAATG AAAAAAAAAA AAAAACCTAC CTTATTTCAA ACTTGAAAAG ATCAAGAGAT TGTGT1TrG TITCAGTT 65 GTrATrTcTC TAAAAG'ITA TGCATGAGGA AAAGTAAAAG TGATIT~AAG AATAAGCCAA ATAAAACAAC CAAGAAAGAC CTCCACTACC CTGGGAAGGA AACTGGTTGG TATTAAGTAG GACACCACAT AAAACAGGTG WO 00/62736 PCT/USOO/08020 154 TrTrTGAGAG GAGAAGAACC AAAATGTAAC TGAGGTrCAA CAAGACATT1A TTTATGCAAT GGCAATGAGA AAAATAAAAA ACACAGTATA ACCATGCTGT ATITGCTATAA GTCATGTTAC ACACTGGGAG ATGGC'FCAG GGGTATThfGG TI1TTAC'ITT TGTTTGGGA GGTITCAA AAAAATTTAG TTAGAATAAG TCCTTTGAGA AACATCACAG TAGGTTAAAC AAAGTI'AGGT TAAATTAGGC TCCTAAG1TT GACTTCTCAG CAAACTCTA 5 CTGAATGTTC TGACTGTAAG CCCAGGATTG CATGACAAAA CCTCTAGTCT GAAGTTACTC ACC'I1GACAG GTTGGTTCTG GAGATGACCA G'ITTCCAAAT GGTCCACAGG TGG'IMC=C AATCCCAGTF AAG=~GTTC CT-TCAGAGCA GCTGAAGGCA CACTGTGAGC TGAAGCTGAA G'IMCCCAAA GGGTGAGTAC AGTCCATGGT ACCCAGCTCT GGGGCCTCCA AAGGCTCACA CTGAATCACT TCAATAGGGA AAGAAACAGT ATGGGGAAGA G'I1AAGAGGA ACTGACGCCT GGATGAAT CCTAGCCCTG CCA=rGATA ACCATGTGCC TTTAAACAAG 10 GTTACTTGAA CCCTCCAACT TCAG'ITrC'rr CATCTATATA AGAGGAATAA TGAAATTGTG 'I1ATC'ITTAT CAAATTGATA TGGAAACTAA ATGTAATTCA ATTAGCATAA GTCAAGGACC FrAGAACAAA GCCTGACTCA TCAGAAATrC TAAGTAAACA TrAGCTAGTC TI7CATATTAT TATCTI1CAGC ATTATCTGTA GTGAGAATCC TTAAAGCCAA ATAGGTGTAA CTGGGAATGA CCAGCTAGT CGGGAAATAA CTATCACATC AGAGCCCCTG AGTCTACTAG AGTATTGGGA GCAAGATGTT CAGAGAAAGA GTGGGTCTCC ATAATAAGCC TTCTTrGCAA 15 GGAGAGAATA TAAAAGTCTA GGAAGCATTT TGACCTCAAT TCTGTC'ITCT ATTCTAGCTC AGTT1CCAGAA 'TTTTAACTCT TTTGA=rG ACAACCCTCT CCAGAAACTG TATCTA1TTC CCTGTTCTGA TTGGTGGTAC AATAGGTAAA TTTAAGACTT GGAAATCAAA G=ICACAT TITAGACCCT GCCATGCCAT TTAGTAAACA GTACAACTTT CATGTCTTAT TCCTCATCTG TCAAA'TrAA GCCATTATTG CTACCTTGCT CTAGAGACTT CAAGGAAGAA TGGACTCAAG GAATCAGAAG AATIT=GTA TTGGAAACT ATATGAGATG AGATTAGGGA 20 GAAACATGGG AACTAAGAGA AAATGTTATC TTrCATT GATrTAAAGA GTATCTATTA TATATCAAGC ATTACTCTGG GGCTrGAAGA GCTTAGAT CACCCTGTAG GACAAAATGG TAGGTAGAAA TTAATGGGTG GATTGTCATG TATGTGTGAT GTGTIIAAT TGCTITAAT TGATCAGTCT CCCTGTAGTA TGAATAATGT A1TTGAGGGG AGCTAATTA AAATTGTGGA ACTCATCTAA TAAACTATTG CAAGAATCTA GAAGAAAGAT AATGACGGCA ATGGTAGTAG AGTTGACAAG TGGAAGACAA ATTAGAAAAA CACTAAGTTrG TAAAAATTGG 25 TAGAATGTTA CCCTGCATAA ATGTTGGGGG AGTTAAGAGA GTCTCATACC AGGGTGCCCA TGTAAATGGT GATTCCACAT ACTGAGATAA GAAATACGAA GAGAAAAGCT GACTGGGAAC AA FrGGITP ATAGTCT TT AAACATCCCA AAGGACATCC TTAGCATATI7 TGAGTrCAGA GCTGGAGATA GGCTTATCAG TCCAAAGATC ACATAGATTT GTGAGTCCGC AAAAGTCAGT AAGITTGACC AAAGGATACA TGTAGATTAG. AGTCAGAAGA GCAATATACA AAAGACAAAA GCTGAGAAAT TATAGTAG'rT TATGGTCCTG GATAAGTGCT CATGAAGGAT 30 CTCAGGAGAA ATGATCACAG GTAGAAAGAA TGAGAAAAGA GTGATATGAG AGAAACCAAG ACAAAGAAAA GTAAAATGTT AAAAATGAGT GAAATAGGCA TACCAATAAT TAAAAATGAG TAAAATAGGC ATACCAATAA CATAAGGGTT AAAAAATAGA GYrCAAAAAT GGGGTGAGGG TAAAGTA'ITA GGAAGGAGTC ATGGCCCAGG GATCAAGTGA AATGAG'rAG ATCTATAGAT CTATTI1CAGT TGGTTGACAT TrAAATGTAT ITGGTITTA ATTCT'rATT G'ITTACAAAC ATTGCTI1T TAAAAAATTA AAP[GTCCAA TTCAATTCAG GCTCACAAGC 35 AAGTGCCTCA TATATACAGG CAT1TGTGG ATCCCAAAGA TGCAATGATA AATAGGACAC 'I1ACTGATCT CAAGAAGTTT TCAGTACCAG AGGAGACGGA CAAGTGAACA GATGAC'FrCA ACATAAGTGG GAGAAATGAG GAAGAAATAT GTGGAGCTAT CAGAACTAAG AAAG=TCCT AGAAGAAACT GTCTTGAAC AATGTCTTAA AGATGACATG TIT1TGGCC ATGTGCAAAA TGAGAGAGAA GGCCACCAGC AAAGTCAGTG TGCTACAGAG CACATGTGTT AAGTGTGGAG AACTGCAAGA AGGAAAGGAA CTACTAGAAG GAAAAAGCAA GATACYFTCT 40 GGGTAACTCA GCCTCCTAAT GATAAATGGC ATAG1TCT CCAGACCTTA GAGTrTCTAAT TAATCTAACA AGCTCATTAG ATCGTGAGCT TCTT1GAGAGC GGGAATCTAC CATGCTAATT CCTT1ATGGTA ACCCTGACAG CTTATCCC AACACTGTGC TrIC'ITGTGGT ACTCAAAAAG AC'FrGTrGAG AAGTGAGTCG AAACTTCATG CTGAC'rrATG AAATCTrAC GGAAAGGTAA CAATATrGTG AAAGCAGAGC '1TTCTGATCA AAACTTCCCA TTTCTCAGAG TGGCTAGTAT CA1T=GTf C CAACCAGCTT CATGATAAGC TATAATGA'IT CCTGTGACFT 45 TACCTAAGAA GAAGCAAAGA AAGGAAAGAG ACTTACCAAA CTGACACTGG GGCCCATAGT ACCCCACATC ACAGTTGCAG GTGTAATTAT TGATGATTTC TACACATTCT CCATGGCCAC TGCATGACCA GGGCTGGCAA GAAGC'TTAA GGAGGTCAGA AAAAAAATAT T'AATGTGA TTACATITA GTACTCAAAG TCATTTC1TTr AGACATAGAT AACCTITTGT CTGAGATGAT TTAAATAATC AGGAAAGG'rr TA1TJ7GTAAA TTCATAGCAT AAAAATCATA TGCTAAAAIT TTTACGTATA AAATACACTA AGCATATAGT CATAGGCATT TA'ITTGC1TT 50 TGGAATGAAA 'rrACCAATAC TAATATTCTG TAACAcTI'AT AGGAAACTTrA GTGGCATACC TGAAACTCT TGAAATI1ACT TGTI1TTAAT GAGTGAGAAG GTTAAATGAT GACCTGACCT CAATCAT7C TGCATGCAAT TATTTCTTGG CAATCCCTJT C'TfTATAGAA ATCAAAGATV AAAAAGTCCA AA TrTGCTAA AACGGTAGAG TCCAAnh7AT AAGAGACCAA ATTAACTATG GTTCATTATT AAAACATCAC TI'GGAAAATG CTGGCTG=I TGGAATTGTA GAAGA=PA CAGAAATATT CATACACCAA AGATAGTGCA ATTTTTATAT AAAATTATAT 55 AAGGTTAGAC CAAGAAGGAA GCACGCAGCA CCACACTCTC TAcT-rCACAA TGTGAAAACT GAGGTGATGT GAGCCTAAGT TTCCAACTGG CCCCAGCTGT CAGMrCTCC TCCCCTGCCT TATrATCAAA GGCACTGATT1 GTCTAGCTCT TCCTCTGTAC TT1CCTACGTA GATCTATCAT ITTrGATGTAA CTrGA1TTAG GGGTATAGCT 'ITTGTGCACA GGGACAAATC TTACACACCA AAAA'rrCTTA GGAGTGACAC GATGCAAGAT TATATAGAGG GCTAGATGTA TITTAGAATG AACCAGAAGC TGTTCTCATC CCCCCACCTT TCCATGGGGT AAATCTGAGT 60* ATTCTCTTAA CCGTGGCCCT TCCTGAGTCT GAGGCAGCAT AGCCGTCTrG TCACTCCCTA CCTGTGTAAC AGAGGGCTGC C'ITAGITI7G TGGCAGGCGT CATCGTrCCA TTTGCCTGCA TC ITTG'IMC TCTGATATA GATCTCCACG CAGTCCTCCT TGTTC17CTT1 GTTGTrGGGC TCACCATCTC CCCAGTTCTC TGCTTCTrCA GTAAGAGATT TGTTFGGTTCC CACCCACGTC CATA771CCTC CTATCTTCCG GA'ITCCTATC CAGTAGTAAG AACGACTGAA AGGCAGAGTC TTCTCCAGAT ACTCAATTTC CGCCTTGTr TGTATGGCAA CTAAATCTGT 65 GTAATTGTCT CGGCAGAATC TT1CTAGCCCT TTGCCAGTT1C ATGGGTIT CAGAATAATG GTAAGTCCAG CAGTCGGTI'C CATGATGTGC CAGGAAATCT GCAAGACATC AGTGTGACCT ATGCAGAC'I ACATAATGTT WO 00/62736 PCT/USOO/08020 155 ACAGCTAAAA AGAACCTAGC ACTACTCCAG GCTGAGCTAG ACACTAGAG ATGAGGAAAC AGAGCCTAAG AGTGTATGTG ACCATCTCAG GATCACAGAA TAGTTGTTTG CAGA'IMGAA GTAGAACCTA GACCTTCTGG CTTGAATATA AGATGCTT ATCTAAGG'rT CTATTGAAA CAAA'TrTAGT GGTITCTAG GTTrATITTFC YITATTAAF11' YTrCTCAAA ATTATCAG GTGAAATrA ACCAACATAT TrAGACATr CATATITr= 5 =rC'I=GTA GCTGTTAATG AMTACAACT AA11TACCGTG TAATATCATA TAACTATACA ATI1?ACGTAT ACrTTTAAT CCTGGAATCA TTTCTTGAAG GCCAACACAT ATGTACCTAT GGGAGAAGCA TAATAAGGAC AGGAAGAACA GTGACATACT TITAAGTAAC CTCT1TACA TAAAAAACAT ITTrArIAC CATAGGAAGA ACTGCTTCTG GAAAAGCCCA ATATACCACT CAACTCTTAT ATATCTAACT GTATAAFIT TAAAAAGAAC AATTTACAAA GCCAAATGGT ATAGGATTAT GAAATrCATT AGATCATGTT CTATACACAA AGAGACTCAA 10 CTGATGATGT TTAATAAACA TATGGACCCA TCAAATATGA GGGCTTTGAA GATATCTAAT TAAACACATA ATTACACAAT GACTTCATAA TAATATATGG CATTCTAAGC ATGGTATGAT CTACATGAAT CACTATrAA TACAGTAAAG AAACAGATAT AATTGATGGT AAAGAGCATC ATAAAATAAA CATTGAAC AGAGTITIGA ATGAGCATTC CACTAGAATG CAAG1TCTAA GAGGGAAAAA ACTGTrGTGT CCACTGCTGT ATCCTIAGTG CCTAGCATAA ATrCACACA TTGTAGGGAC TCAGAAAATA CCTGTTGTAT GAAAAGAGCA CTAAG VTTCT 15 ATGTGACACA GTGCAGACAT GGCATAAGGA ATGTGTGAAC GGGAGAGTTA GCATGTrTGC TTGGCTAGAG CTGAAAATCC AGGCTAGGGA GAAAGAAGAC ATrAGTTTAC TTAGGAAATG AAAAACCAAG TT1CAAAGCTA TrGCTGGAGA GTCTI'CAAGA ATCAGATATA AAATTTGTCA CAACAATGGG AGAAGGACCA AAAAATGATA AACCCCCGTC CC'ITAATAAG CTCGTATTGT AATTGTAGAA ATGACAITrAA TGTACACTGA ACTATGAATA AAAAATAGAA AATGAGGTGC TAAATA'IMG GTACAGATTG TAAGTACCTF AACAGAGATrr TCTTAATTAA 20 CATTATTCCT TrATAATrGA GGGATTGT GGGGTTA FTG GGATrTGAAC TCTACAGCAT GGGCTATI'AT AGGTTAAAAA TAGTGYI'CAG GAG'1TTCTGG GGAAGAACTA AAGGTAAGAA GAAAAGAGAT GTITACAGAA GGGATAGAAT TAACAGCTCT GTGAAATAAT 'TrCCCFrAG ACTATGTATA ACTAGTGGAT A'TTrAAGAAA AATGAATATA AGTAAAATAG AC=AGCGAT ATATAAATAT CATAACATAC CACAACAGAG CATTGTCCAC CCCCACAACT TGAAGATGTT CCATAAGTCC CTCTGGGTGC TCTGACAT CCATGGAAAT ATCTGCAAAT 25 GAAATACAAA A'ITATKITIA GATGTATACT C'FrAAACCAC ACKITTATAG CC'ITTGAGGT GGTGCTYFACA ACTTTCTTAA TAATCAGAAT AAAACACATA TGTCTACTAA CCCTGTCTGA GGTAACAGGT FTCTCAGACA TAGATGAAAA ATTACTTCAA Ar=ACATCA GAACTGATGC ACAG'TrTGT 'IMrGTTrCTAT 'ITATJTPA CGC=TAGTC TCAAGTT1GCT AATCGGTACT GCCCTGAA17TT CTATGG 'ITTGGTAAYI? TTTATACCTG CTTTTCTGCT GAGCTATTAG ATAAAACTAT 'TAATA IMA CTATGTATAT TITAAAGT ATFGrrGCTG 30 CTI7AATAAC TA'FrGATGCT TATA'ITTAAT G'ITATAGCCT CACTCTTGAT CATAATGGGT CAATGCCTCA AATACCTAAA AAAAAAAAAA A FTAGATAGC CAGACACCAG GAAAGAAAAG TAT1TCF TI1?AATAAAA AGAAATACCT TITGAGCAA CTGAAATGAC AAAGTCACAA A TTCCTGCA CACCTTAAAA TATACTTAAT GTAAATGACG AGTI7AATGGG TGCAGCACAC CAACATGGCA CATGTATACA TGTGTGACAA ACCTGTATGT TGTGCACATG TACCCTAGAA CTTAAAGTAT AATTAAAA AAA'ITCTATC TI'CCAAAGCA TATCACTTCT 35 CAGGTAGACA CAGTGTTTAT TGCAAAAGAT CTGATCAA TAGTATCT TCAAGAGTCT CCCCAGAGAC AAAGTCAAGA AGAGGAAATC AGCATATCTG AGAAGAAAGA TITCAGGATC ACTFTTTG AGGGTCTGAG AAAATGTFTA G TCTATAT TA'1AAAAC CAGAATTGAA ATGGGGTGAT TCCTATCCT11 GCCACCTGCC TCTACAACCC CAAGAG'ITTC TATCTGAGCA TCTAAACGTC YI=AGGCTG AAAGGCTCAC CATGGCYTTG CTVrGGTCCTT CTCTAGTT1CT TCTGCAGCCC ATTGAGCCTC TTGAC1TAGC ACAAGGGTCT CAGGTCCTTG 40 CCCAAAGGGA GTGTGCTGTG CTGCAGGTAG ACTGCACTGA ATGTCAACAG AAAGCCTTGC 'TTrCThrCAT TTCTCTAACC CAGTCTCACA TCCTCCTCCT CCTCCCC1T TCCCTCCCCT TCCTCCTGCA CTTCTC'TrTC CTC'TTCCCC ACCCCTTCC TAGACTGGCC TCTATTGCCT CCCACTGAGA CAAAAATGAA CTGCTGATCA GAAAGTAATG TGACTAGATT CTCTCTTCCT TCCCTCC'Tr CTATCCTTCC 'FrCCATrCTC CTATGCATCT 'FrCCTTACCC TCCTCCTCCT TCACTCATTG TTGTrGCTGT TCTTCT7CCT CT=IIC CTCCTGCTCC 45 TCTTCITCTA CTI'GT]?CTIG TTrGrorr TGT7GGTrC TTGT-FCTCCT CTrCCTCCTT CTCTCTCTCC TCCTCCTCCT TCTTCCAC CACCCTCCCC TATCT1TTTTC ATAAATGCTA AACTAACTCT TGGCTACCTG TGGTAAATGG CCCTTGGAAA TTGCAAATAC TACAAATCAA AACTGCATTrT CAGACATATT TATGATGTr GCAAAACTTC AGTAGAGCTA AGCAGTGGAC T-rGACTCGTT TCGGT7CCT CACCTCCGTC =TCCTTGCT CACCACCTAG TGGACGTCCT TGTTAGTGGC AC'FrCCTGAA GTTAACCCCT GAAGAGAGCC CATGCTCTCT 50 AGCTTICAC CGTGTAGGTTI TGGGAGCCTA CAAGTACCTT TAATATT 7 GGACTATAAA ATGAGATGGT TTTATAAGAC TGCATGTGAA ATTAGGACCC ATATGATGAA GGACAATAAA AAGGAAGACC CACTGATGTG AGTCAATGAG TCAAATGCAA ATCAGA=~G CATTTAGG AAAATAATAA TAACAACAAC AAAAACTCTG AAGCTCAGCG CCCCATATTT ATTATATITGT TTAATCTTTA TAACAGCTCT CTGCTATAGA TATGAYTATT ATCCCCA11?C TAAAGAGTCT CAAAGAGG~r AAGAAACAAA TrCAAAAACT AGCGAAAGAC AAGAAATAAC 55 TAAGATCAGA GCAGAACCAT AGGAGGTAGA GACACGAAAA AGCCTT1CAAA AAATCAATAA ATCCAGGAGC TGCATITTGA AAAGATTAAC AAAATAGATG GACCACTAGC TAGACTAATA AGAAAGAAGA ATCAATAGAC ACAATAAAAA ATGGTAAAGG GGATATACC ACTGATCCCG TAGAAATACA AACTACCATC AGAGATL'ACT ATAAACATCT TTACACAAAT AAACTAGAAA ATCTAGAAGA AATGGATAAA TI'CCTGGACA CATACACCCT CCCAAGACTA AACCAGGAAG AAGTCAAATC CCTGAATAGA CTAATAACAA G'ITCTGAAAT TAAGGCAGCA 60 ATL'AATAGCC TACCAACTAA AAAAAGCCCA GGACCAGATG GATFTCACAGC CAAA'I1?CTAC CAGAGGTACA AAGAGGTGCT GGTACCATTC CTTCTGAAAC TAUTCCAGAG AATAGAAAAA GAGGAACTCC TCCCTCACTC ATITATGAG GCCAGCATCA TCCTGATACT AAAACCTGGC AGAGACACAA CAAAAAAAGA AAATIT7CAGG CCAATATCCC TGATGAACAT CATTGCGAAA ATACTCAATA AAATACGGCA AACTGAATCC AGCAGCACAT CAAAAAGCTT ATCAACCACA ATCAAGTrGG CTTCATCCCT GGAATGCAAG GCTGG'ITCAA CATACACAAA 65 TCAATAAACA GAATCCAITA CGTAAACAGA ACCAATCACA AAAACCACGT GATTATCTCA ATAGATGCAG AAAAGGCCTT GGATAAAAIT CAACACCCCT TCATGCTAAA AACTCTCAAT AAACTAGGTA TTGATGGAAC WO 00/62736 PCT/USOO/08020 156 GTATCTCAAA ATAATAAGAG CTATTTATGA CAAACCCACA GCCAATAGCA TACTGAATGG GCAAAAACTG AAAGCGTTCC C=rAAAAAC TGGCACAAGA CAAGTATGCC TCTCTCACCA CTCCTGTTCA ACATAGTATT GGAAGTrCTG GCCAGGGCAA TCAGGCAAGA GAAAGAAATA AAGTGTATTC AAATAGAAGA GAGGAAGTCA AATI7GTGTCT GTTTGCAGAT GACATGATTG TATKITTAGA AAATCCCATT GTCTCAGCCC AAAATCTCCT 5 TAAACTGATC AGCAACT-rCA GCAAAGTCTC AGGTTACAAA ATCAATGTGA AAAAATCACA AGAATrCCTA TACAGCAATA ATAGACAAAC AGAGAGCCAA ATCATGAGTG AACTCCCATT CACGATTGCT ACAAAGAGAA TAAAATACCT AGGAATCCAA CTrACAAGGA ATGTGAAGGA CCTA3TCAAG GAGAACTACA AACCACTGCT CAAGGAAATA AGAGAGGACA CAAATGAATG GAAAAACATT CCATGCTCAT GGGTAGGAAG AATCAATATC ATGAAAATGA CCATACTGCC CAAGGTAATT TATAGATTCA GTGCTATCCC CATCAAGCTA CTACTGACTT 10 'TTTCACAGA ATTAGAAAAA AACTACT[A AMTTTCATAT GGAACCAAAA AAGAGCTT7GT ATAGCCAAGA CAATCCTAAG CAAAAAGAAC AAAGCTGGAG GCATCATGCT ACCTGA=TC AAACTATACT ACAAGGCTAT AGTAACCAAA ACAGCATGGT GCTGGTACAA AAACAGATAT ATGGACCAAC GGAACAGAAC AGAGGCATCA GAAATAACAC CACACATCTA CAACCATCTG ATC'IIGACA AAGCTGACAA AAAGAAGCAA TTGGGAAAGG ATTCCCCATT TAATAAATGA TGTTGGGAAA ACTGGCTAGC CATATGCAGA AAACTGAAAC TGGATCCCTT 15 CCTI7ACACCT TATATAAAAA TI'AACTCAAG ATGGATI'AAA GACTFTAAATG GAAGACCTAA AACCATAAAA ATTCTAGGAG AAAACCTAGG CAATACCATT CAGGACGTAG GTATGGGCAA AGACTTCATG ACTAAAACAC CAAAAGCAAC AGCAACAAAA GCCAAAATTG ACAAATGGGA TCTAATI'AAA CTAAAGAGCT TCTGCACAGT AGAAAAAAAA AAACTATCAT CAAAGTGAAC AGGAAACCTA CAGAATGGGA GAAAA'TI= GCAATCTATT CACCTGACAA AGGGCTAATA TCCAAAATCT ACAAGAAACT TAAACAAATI' TACAAGAAAA AACAAACAAC 20 ACCATCAAAA AGTGAGTGAA GGATATGAAC AGATGCT7CT CAAAAGAAGA AGTIATGCA GTCAACAAAC ATATGAAAAA AAGCTCATCA TCACTGGTCA TTAGAGAAAT GCAAATCAAA ACCACAATGA GATGCCATCT CATGCCAGTT AGAATGGCGA TATTAAAAA GTCAGGAAAC AACAGATGCT GGAGAGGATG TGGAGAAATA AGAATGCTTT 'ITACAGTGTT GGTGGAAGTG TAAA TTAGTT CAATCA'ITGT GGAAGACAAT GTGGCGATT CTCAAGGATC TATAACTAGA AAAACCATr GACCCAGCAA TCCCATTACT GGGTATATAC CCAAAGGAITF 25 ATAAATCAYI' CTACGATAAA GACACATGCA CACrrATG'rr TA FTGAGGCA CTATTCACAA CAGCAAAGAG T7GGAACCAA CCCAAATGCC CACCAATGAT AAACTGGATA AAGATGATGT GGCACATATA CATCATGGAA TACTATACAG CCATAAAAAA GGATGAGTTC ATGTCCTITG CAGGGACATG GATGAAGCTG GAAACCGTCA T7CTCAGCAA ACTAACACTG GAACAGAAAA CCAAACATTA CCCAT7CTCA CTCATAAGTG GGAGT-FGAAC AATGAGAACA CATGGACACA GGGAGGGGAA CATCACACAC TGGGGCATGT CAGGGGATGT GGGGCTAGGG 30 GAGGAACAGC ATTAGGAGAA ATACCTAATG TAGATGACAG GTI'GATGAAT GCAGCAAACC ACCATGGCAC ATGTATACCT ATGTAACAAA CCTGCACG'IT CTGCTCATGT ATCCCAGAAA TTAAAGTATA A'TrAAAAAA AGTrAAAAA AAGAAAGTTG CC'ITAGTCAC ATAACTAGTA AGAGACATGG FTGGGAATF GAACAGAGGC CAATCAGTIC CAAATCCATG CTCTTGATCA TTAAGCTGAA CTTATGGCAG GAACTTGGAA GACATGGTAA AATGGGGAAA AACGTGGAGC CAGGGAGACT TGTGAAAGTG CCAGTGCTCC CACTATACCC TGAAAGAAGT 35 ATCTAGACTI' ACrTTTCT AAGTCCTCTC CTCTAATTCT CTCAATCTCT CTCTCTCT CTCTAAGAGA TGGGAATGCT GCTCTGTCAC TCAGGCTAGA GTGCAGTGGT GCGATCATAG CTCATTGCAC TCAAGGAATC CTAGGGTCTA GTGCCCCTrC TCCCTCAGCC TCCCATGTAG CTAAGACTAC AGGCACATGC CCCAACCCTC GACTAATT TITATTT An=ITGTAG AGACAGGATC TCACTATG1T GCTCAGGCTG TAATTCTGTC TTGAAGCTTG TCCAATCAGG C'TrCAGCCA CACCAA ITCC CTGAGACTGC TCTCACCAAG GTCCTACACT 40 TCACTAACAC AAACAGCCTA TTCTCCATCC TCATC'ITACT TCACCAGGGA GCTCCTGG'rr 'TCCTCCTAC TTCACTGGCT A TrC I1CTG TATCATGTGT TGATTCTCCC TCATCTCCCC AACCTCCAAA CCCTTGGAGT ACTCCAGAGA TCACCGCT GCTCTI'CTGT GTCTAACCTC ACTAACTTGG TGGTCCAATT CACACTCTTG ACTrGAATA CCKITTrAAAT GCGAACGAAT TCTAAATTCT GTACAACCAG AACCA1TCTC CTGTAGCCAA ATGCCTACTC AACATCTCCA TCCCCAAACA AA=~AGTTG TTCAATAAGC CTCTCATATT FTACATATCC 45 CAAACTGAAC 'FrCTGAATTT CTCCTCCAAT CTGTAGGGCT, CTTCCCACAG CCITTCCATC TCAGTGGAT7 ATAACTCCAT CCTTCCAGYT ACTCAGACCA AAACTITGG AGTTAACTGA GACACCTCTC TITTT=CA CAAGTCATAT CCAATGTGTC AACAAAYITT GGTAGTGGAA ATATTGCGGG A~fTTrrAAG AAATCAGAGA GACCGATGGG GITCAGGAGG ATA TI7ATTA TTTAGGTGCA CTGGCCAAGT CAGATI7AACA TCCAAAGGAC TGAGCCCTGA ACAAAGAGI17 AAGTTACCTT TTAAGCATTT TGTGGGGTGG GAGAGAGGGG TATCTGTGCA 50 GGGGGAAGCA TACTACAGAA GTGAGAAATA AAGACAGTI'A T7CAATTAAT TGAGACATGC ATTACATCAT TCTACTrr TCAAGAAGAA ACATGTIIG CGACTTGAGT TTATCTGTCT AGTGACC11'G CAGCTGCACA GCTAGAGAAA CAGGGTC17C ACAATGCCTG GGAAAGGAGG AGAGGTAAGT CTCACTAGCC ACAGAAAAAC AGGCAGTTAA 1TTTAAAGG GCTCCAGCTC TTTCTCT1rC TCAGGGGGAG 'rTGGGTI=G TTACATACAA CTGAGTTTCC GCTTACACAT TA'1TTAA1TT CT1TAA'ITC CTG FTCCAAA AGAAGCCAGA TACAAAAGGT 55 TACATGTI'GT CTGATTCCAT TTATATGAAA CATATAGAAG AGGTAAATCC ATAGAGACAG AAAGTAGATr AGAGGT7CCC AGGGGCTGAG GAAGAAATGG GGACTAACTG C'ITATAGGGT ACAGAGThJT CTTCTGATAA AAATATI17G GAACTAGATA GACATPTGT TAGGCCATFC TrGCA'rrGrr ATAAAGAATI' ACCTGAGACT TGGTAATTTA TAAAGAAAAG ATGTTTAATT GGC'ITACACT TCTGCAAGCT TI7ACAGGAAG CATGGTGCCG ATATCTGCTC AGCTTCTGGT AAGGCCTCAG GAAGCTI7ACA ATCATGGCAG AAGGTGAAAG GGGAGCAGGC 60 ATATCACATA GCAAAAGCAG GAGCAAGAGA GGGATGTGGG GAGGTGACAG TCACTTTTAA ACAGCCAGAT =TGTGAGAA CTCATTCACT ATCATGAAGA CAGTACCAAG AGGATGGTAC TAAATCA'I1C ATGAGAAACC CCACCCTCAT GATCAAAT.CA CCTCCCACCA GGCCCCACCT CCAACACTGG GGATTACAAT TTGACATGAG ATTTGAGTGA GAACACGGAT CCAAACCATA TCAGAGATGG TGGTTATACA ATGCGATAAA CGTCACTGGA TrGTACAC Fr TAAGATGGTT GTI1ATGTT GTGTGAACTT CACCTCAATA AAAAAAAATA TTAATGTAC 65 ATT1CAGCCAA AAGAAGATTT GGAATAGGAA AGGTCATGGA GATATATTAA CAGCCA'TI7TG ATGGGTGGTA AGGAAAAGAG TGGTTATTAG ACTGTTTGT GGCCCTCAAA AGGTAGAACT AGATCGAG'IT GGTGAGCATT WO 00/62736 PCT/USOO/08020 157 ATAAAACCAT CACAAAACCC TGGAGAGAGG ACCCAGTGCT GAAGAACCGT TTGCCTGCCA TGAGACATGA GGGAAGTACC AGTGAATGCC ATTGAAAGCA GCATCCCTGG GTCCAAGGGA TGGTCAAAGG ACCACTACCC AACCCTTCCC TAGCCTACGC CTCCATTACA GATGACCGCA AGATTTATTT GCTCATTGCT GCCAACCAAG GCTGCACTCA CTGCAGTTGC TATCAGTTTA TCATGGGTAA AAGGAATGTG CAGTAGAGAA CTAACTAACT 5 GCCCACCTAC CTCCACAATC CTATCAGGAC AAATCACCAT GGCTCACATT TCCTTACATT TGGCATGTAA GCCCCTCTTA CTGTCTGTCA TCTATCTCCT. ACACAGTTCA CCTAAACTGT TCTCTCCTGA CCCAACCTTG ATTTTCATCC CAAATGCTTC CTTGCCATCT CTGGGATTCC TGTCTTCACC ATCACCAAAC TCCCCTCAAT CTTCCAGTTT CCTGTTCAAA CTTTTCTCCT ACCTCCTTGC TTTGTCATTA GCCCGACTGC CTCCCTAGGA CATCACTTCC CCTGCAGATC TCTCAAGATG ACAATATTTA TTCTCCACAC AGCACATACT TCAGGGTTGG 10 AAGGCAGGGG CAATCTTCTC CTTATAATG AGTGCCTCTT ATATATGTTT ATTCATCTGC CCTCTTGTAA AACACACACA CACACACACA CAAAGAAGAA ATAAAATAAC TCTGCTTCTT TGAAGCTTGT GACACTGAGA TAAACCATCT CACTGTCCTC ATTGTAGTGA CCTCTCAACT CCTCATGCAA GATTGGCTT GGCACCTAGT TCCTGATCTT CCTTTCCCTG TAAGCACTTC TCATAGTCTT ACGGGACTTC ACCATCCATG GCACAACCAA TACCACAGCC CAGATCCTCA GCTCTCCAAT GACATTTTCC TCCACTAGAC TTGAGCTACC TCCTTCCCTA 15 GGCACAGCCT CAACCTCGAC AACACCTAAG ACTGTACCGT CTCTAAAGTC ACATGTTCAA ACACTTCACT CTTTAACCAC TGTCTCCTAT TCTTGCAAGT GTATTGCTCA AGTATCTCAT TGCAATGCTT TTTACTTCTA CCTCATTGAA CCTCCAGGCC ATTAAACATT TCCTTATTTC TAACCATCAG GTTTCTCCTT ACTTGTTTGT TrGTTTATTT GTTTCTTT TI' JTTTTT T TTTGAGACAG GGTCTCACTC TGTITGCCCAG GCTGGAGTGC AGTGGTATGA TCTCGGCTCA CTGCAGCCTC CATCTCCCTG GTTCAAGTGA TTCTCATGTC TCAGCCTCCC 20 GAGTAGCTGG GACTACAGGT GCATGCCACT ACGCCTGGCT AAGATTTTGT ATTrTTTATTA GAGAAGGGGT TTTGCCATGT TGGCCAAGCT GGTCTCGAAC TCCTAACCTC AGGTGATCCA CCTGCCTCAG CCTCCCAAAG TGCTGAGATT ATAGGCATGA GCCACTATGC CCCACCTGGT TTCTCCTTAT TTATTTCAAG TCTATGCTGC ACTATTAAAA CTGCCTFGAC AAAAATTATA ATAGTGAGAA AATFATGACA GTGAAAGAGA TCTGAAATAA TCAACCCCCA TCTTGCCTTT ACCTTCCAGA CTGCCCTTAA TAATTCCTGA GCTTGGGCCA AGCTATCTTT 25 GGCAGAAATT TAGTTATAG TTTAAATGAT AATAGCCCTT CTCCAAAACT AAACTGCCTT TGTAAAACTA ATAAAAGACC ACCAATGAAA GGTTAGGAGG ATGAGAGGAG CCTGAATTCT GCTAAGGTGT AGATGTAAAC AATTACCAAC TGTTA'TTCCG GAGGTCACAA GATTTGCAAC ATCGCCAATT ACTCCTGCAG ATAACAGCAC TATCATAGAA TCTGATTGGC CTTTTGAGAT GTCTTTTCAG ATTCTTACAT TTCAACTGGT GGCTCTACCT GGACCCATCA ACAAGTCCTG TGGCTCCACC CAGAAGCAGA CTTAACATGC ACAAGGACCA TTTTCCACAC 30 CGCTATGATT GCATCCCAAC CAATCAGCAG CAACCATTCC TCTGCCTGCC AAATTATCCT TGAAAAATCT TAGCCTTAGA ATTTTGGGGG AGGCTGATTT CAGTAATAAC AAAACCCCGG TCTCCCATTIT GGCTGGCTCT GCATGAATTA AATTCTTTCT CTATTGCAGT TCCCATCTTG ATAAATCACC TTTATCTGGG CAGCAAACAA AAGGAACCCA TTGGACAGTT ACACTGTTGG CAGATATATC TTGCTTCCAA AATTGGATTT TTGTTTAATG AATTTATTCT GTTTTCTTGA TATTTACAAC TGTGAATGTT GTGTCTGAAT TCTCTTTATT TCTTGTTGAA 35 AAGAACTATA TTGCTACAGC CAGTACATAC AGATGGATAG CTAATTACTC AACACGGGGG GATGTGACCA TCACCGCACT GTGCAAATGA ATGTTACCCA TTGTCCACTT TTCCCAAACT ACATAGTGTT ATATGGTATA TGACCCAATC AACGGTGGCA AAGCTCCAGA AATACCACAT AGACATCAGG GACACTTTAA ACTAATCAGC CTATAGTCCT TCAGTAA TTTCCAAACC TGGTTGTGCA TCCAAATCAC TTGGTAACAT TAAAAAAACA AAAAAATATA CACGCAACAT TCGCTCCCAA TCCTACTGAA TCAGAATATT TTIGGGTTGGT TCAGGAACAT 40 TCAGGAGTTT TTCAGGGTCC AAGGTTTATA TAATTTGAGG TCTCTCT1TG AGAAAAGGAA CGTAAAAGCG TCTTGCTTTT ATAGATCTTA CAAAGATGTA TTACCATGTA AACACATTCC TAGGACCCAG GCCCTTGTAA TTTAAAGGTT TATCTAAGTA ATGGGCCCTG AAGCTTrAATT TTCATTATCT TCAGGGCAAA TTACCTGTGG GTTAGGGTTT AGGAATATAT CTCTCTGTGT ATGTGTGTGC ACATTAGCAT GTACGCTTGT GTGGATTTT TTTTrTrT TTTTTTTTTC TGAGACAGAG TCTCGCTCTG TCGCCAGGCT GGAGTGCAGT GGCGTGATCT 45 CTGCTCACTG CAAACTCCGC CTCCCAGGCT CAAGCGATTC TTCTGCCTCA GCCTCTTGAG TAGCTGGGAC TATAGGCACG CACCACTATG CCCAGCTAAT TTTGTATTT TTAGTAGAGT TGGGGTTTCG CCATGTTGGC CAGGATGGTC TTGATCTCTT GACCTCGTGA TCCACCCGCC TCCACCTCCC AAAGTGCTGG GATTACAGGC GTGAGTCACC ATGCCCAGCA CTTGTGTGGA TGTTTTAAGC TCCCAGGTGA GTGAATACAA AACTAGATCT TTCCCTTCTG TAGCATCTGT ACTGTTTACT CTATGCATCT CAATATTTTT TCTTTTAGTA TCTTTCCTTT 50 TTCTCTCTTA TTACTTCCTC TTGTGCTATT TTTACACCTC CTTTTTTAAA AAATTTTC CCTTTTATTT CTATTGACCT TTAGCCCTCA CAATGATrCC TACAAGCCCC AITCTGTAA ATGGGGATTG AAATAATrGC TGGACTTTTG AGAGATAGAT ATATTAAATT GCAAACTGGC AGTAGTGGGG GCAGTTGATA CATAACTAGG TTTTAAAGTC TAGCCTTCTG AGACCACTCA TTCCATTTGT GAAAAGTGAT TCTACTTCTT ATTATGAGCC AAAATATGCA TTCATTCACC CATGCATTGA TTTATTCATT CAATAAATAT TTGTTGGATG TCCACTCTGT 55 ATCAGGAATG TGCTAGGTTC TGGGAATACA GCAATGAACA AGGTAATTTT TCCCTACCCC TAAGGAACTT AGAGTTTAGT GGGGAAGACA GACATTAAAC AAACAATTGT GCAAGTAATA ATCTATAATT ATTTATTACA ATTAAAGGAA GGAAGAGACA TATGGATTAT GAGGGCATTA AAGAGGAGAC CTAGTGTAAG TAGCCAGTTC TCGTGAAGGG ACATGTATTA GTTGGAGTTC TCCAGAGAAA CAGAACCAAT GGTGTGTGTG TGTGTGTGTG CGTGTGTGCG TGTGTGTGTT GGGGTGTGGG GGTGTGGTAT TTTTTATAGA AATTGTCTCA CACAATTATG 60 GAAGCTGAGA AGTCCCATGG CCTGCTGTCT ACGAGCTGAG AACCAGGAAA GCCAGTGGAA TACTFCAAAG TCCAAAGGCC CTGGAACCAA GAGTGCCAGT GTTGGAAGGC AGGAGAAGAT GGGTGTCCCA GCTTAAAAAG ACAGTGAATT CACTCTTTTT GCTCTACATA GGGCCTCAAT GGGTTGGATC ATGGCCACCC ACATTGGTGA AGGCAATCCT CTTAGTCTAC CAATTAAATA CTAATCTCTT TGGAAATACT CTCACAGACA CACTGAGAAA TAATGTTTTA TCAGGGTGAT AGAAATCTTC TGGAGTTAAA CAATGGTGAT AGCTGTACAA TCACATACAT 65 TTTTAAAGGG TGCGTTTTAT GGAAAGTGAG TTTTATCTAA ATAAAATTTC TAAGAAAGAG ACTTAACACA GAGATAAACA TAAGCACATT TATTGTCAAC CTTTATAGTG TTATGTCAAA TAGGTCTGAC ATAAGCTTAA WO 00/62736 158 PCT/USOO/08020 ATAAATATAT AC TTAAAAA FrATAAAATA TF=AAGTTA TAATITAAAA TTCTCAATAA AACTCAAACA CAAACCACAC TGGTAT'CA CACAGCTAAT TTCTAATGCA GM~ACATAA ATAYJTACAA CACTTAAACA AM~CAAAGA AAATAACACT GTATTCCATA CATAGCCTGA TCACAGTAGT TG117CTCTCT TAM~CCCAG AGTT=CTG CCCCTAAA AGAACCTCTG CTGTTCTGAT CCTATCACA TCTCTG1TI GACTGTTGGC 5 'ITTGTrG'rrG CCAGTGTL'CA GCCAGAACTT CTCTGAAACT 1TITITCAA CACATGCTAA GrrAATGGAA GTGTAGGAGA G7MTGATTC TCACACTCCT CAAGGCTAGA GCAGCn7~GG CAATTACTGA CTGAGAATr TrCA'FrGCCA GTGATCAACT GAAAACTGGA GATTCCTrG GAA rGTTAA. ATCTGCTTAT AAATAAACAT AAATGCTTGC TCACACAGGC ATTCCTCTCT TCCAGAGCAC CCTAACATAC AGAAGAAAAC AAATAGGGAA TAACTATTAG ACATCTTCAT TCG'TrAAAAA. TCTACCAGAT GACTC'IrA CATGGTGAGT TTCTATrGTG 10 AATlTAAAAT CTI1CCATAAT ATACAAGAAT TATG=IACA TATCATATCT GACAAACATC 'ITTGTAGGAA TGCAAAGCAC ATCCATCFI1 CTGTATTCTT TTCCAACAAA GACATTCATA AAA'frATACC =FGTGTGTT TGCAT'rrATG CTTTTAT7AG TT1CAAAACGT TI7GGCCTCAT GGAAGTETT CATCGTGGAA ACCACATAT7 TCTGAAAAAA TATCTGACAA TATACAAACC TTCCATTCAG ITTIACTCT CCAATTCTAC CATGT=~CA AAAAACAACT GTAGTAAAAA CACTCAGAAC 'TrATTCTGG TTAACATCAT GCCTTGCTAG GGGACAATAG 15 TTTCCCTTr TGAAATAAAT TTAAAACAGA TGTAACATAA TTTG'ITAATA AACAATGAGG GGGTAATCTA GAATAAGTAA CTiTTACCAT ATCATAGTTG ACAGCATrA CAAGTrITI AAGTCCCTAC CACACTTGTA TTGAATGAAG AAGTATGGAA GATTATAATA TA'VrCAATGC AAGTAAAAAT ATCACAATCC TTAAGAACTC 'TTAAGAAGC ACTGAATCCC ATAGGGATGA AAGTGATrAA A'ITGTGCATA GTAACCCTCG CACAGAGCAT TCAGTAGGAT TTGCACCATT AACAACCCTC CATGCATTTG CCTGTGGGCA TTCAACATCT GTCATTTT 20 TAAGTTIATAA TATTTAGT CATTT=C CTCTAAACTC TGGATAATTrA TTAYrCATTC TTATGACAGC AACTGTGTAA TCAGCTGTCG AAACACTGTG AAGGGCAAAA GAAAGAAAGC CACAAAATAT TGTG TTCTG TGCCAAGATT TTACAGCGAG CAAGGGAGAG TTAGAAAAGG AATTCTGAGA MTCAGAGTC PPGGTCTCT CACCTTTGCT TGGAAGAAAA TATCCTICC CTTCATTAGC CAACACTITC TrGATCCTGA GAGTAGGAAA GGGAACACTG AGTCTITCA GTTGAAGGCC GTCCTrGCCT GCTGGACTIT GATCTATTGA AGTGGTGATG 25 GGTGTT1GCGG TTTCAGCCAT AAAGGCATCT GGCATAGTAG GCAAGAAGGG CCAGAGACCC GAGGAGAGTT ATCTGTCTCT GTTAACTTCA GTGTATCCCT CTAGTTCCCC AGATGCACCT G'ITTCTGTAA ATATAAACAT GCATGTCATC AGAACACTTA ATA1TCTGCA TACTGATCAT GACAACAAAA TGTACCTCT AACACAGACA CTCTCACTAG GATAGACCAT GTAGGAACAT CGAATrCTAT TCAGYrAGGA CAGTGATGAT GTCTACATAT TATACCTCTG TCAAAACCTA CAGAATATAC AACACAGCAC AGAGTGAATT CTAATGTAGC CTGTGGACAT 30 TAATGAATAA TAATGTATCA ATATFTGGCCC ATCAGTTGTA ACACTAATAT AAGATGT~rAA TAACAGGGGG AATrGAAGGG GTGGTGGGGA GATATGTTGG AACTCTTTGT GC'ITTCTGCT CAA'TTrCT GTAAAC'rAA AACCGCACAC ACAAAAAAAG 'ITArIAAT 'T1TAAAAA GTATTCAGAG GGACTI'GACC YITCCAAA'rr CTCTCAAAGC AGGTCGGAGT AGTI7AAGAAC ACAAATIA GAACCAGACT GCCAGAG'IM GAATCCTGGC TACACCACTT ACTAGCTI'G AGA ITTCAGA CAATITACTT AACTTCTCTG TCTCAT1TC TTCATCTGTG 35 TGATAAGAAA TAAAGTAACA GGCCAGGCCC AGTGGCTCAC GCCTGTAATC CCAGCACM~ GAGAGGCCAA GGCGGGTGGA TCAGGAGTIC AAGATCAGCC TGGCCAACAT GACGAAAAAA TACAAAATCT CTACTAAAAA TACAAAAATT AGCTGGGTGT GGTGGCAGGC ACCTGTAATC CCAGCTACTC AGGAGGCTGA GGCAGGAGAA TTGCTTGAAC GCAGGAGGTG GAGGTTGCAG TGAGCCAAGA TCATGCCACT GCACTCCAGT CTAGGCAACA GAATGAGACT CCATCTCAAA ATTAAAAAAA AAAAAAGTAA AAAGAAAAGA TAAGAAATAT AGTACCAGCC 40 CCTATCTCAG AGTTCCTAGC TTAGAAAAAT TCCCAGAATA TAATAAGTGC AATGTAAGGG TCAGCTATCT TCA'FrAITAT TATCTATCAT AAATGAAATI' ACACAATAAA GCTAGATCCG ITTCTTCCT CTCCTTCTAC AAAAAATAAA GCAAC'ITTCC AGAACAATAC CCAGGTGATG ATTTCTCCCC TGCTCCCTCC CTAAGATAT7 GGCAAGITTG GAGGGTTCAA GGAGAAACAG AGCATGTAGA GAAGATACCT CTCTCATAAC CA I=TGTGAT TTACAAGTCT TACCTGATTC =FTGAACT'f AAAGGATGTA AGAAGGC'IT TGGTAGC17C CATCTGATTC 45 AAGGCTIGG CAGCTGCTGT GGAATACATG AGAACACTAG GTAAAGCACT GTCTTCCAAC ATGAAGAGAG AAAAATATGT GGAATGTTCA ATGGCATGCT 'rTGTATAAGA ATGCAACTA CCTGGCAGGA ACAAATTCT 'ITGCTGCAAA. AGAAAAGACA AACAACCATI' AATTCAGACT AAATGAC=T TAAGGATATA TTAAATCCAG ATACAATATG ACTrAATTCA TCAAGTGTTG CAAACTCGAT GC1CAGGGC CTC TGTAATA ATCAGAGCAC AAGCATGGCT CTGTGGCATC TAGGGTAAAA TGCAAA.GTGC ACAGCCATCC AAAGGGCATA GCAGCTTCCT 50 AATGCCAGCA AATAGCTACG GGGTCATCTT GCCCAA'I1CA GCTrCCCAAT7 TITCATGAGA AGTCCAAAGT CTTAATTTAA ATGTGAGATT TCCTArITG TAAACGTCAG AACTTAACTC AAAAATG'Tr TAAGTACTCT TAAACATGTA AGCCAAACAA ACCATGAGTG TAGTCAGATG TGCTTCCATA TrCCTTATGA GAGACTCTCA AAThrTAAGCC TGTACTCCAA ATAAATC TCC TVAGGAAGAA TI=ATCCAT TTCCTTAGA GTGCTCATCA TGGCAGT'rCC ATTGCACAAT TCCGGGAGGC ATCATATAAT TCAACATGAA TAGCACCCCC TGGAGTTGTA 55 CAATATTAGG CACGACTAAC NTAITT CCTGAAACAC 'I1CCCACACT GAGT7GTACT ACTAACTCTT TFrCTTAATAC YrCTGCTTAA TTATACTGCA T1T~ATCCAG A ITCTAA'ITA TrG'IAAAT CAGTAAGCAA GACCATGACT TATCAATGAG AAAGAAATGT ATITTCAAAA ACA TITGA AGTACATTCA TAAACTTCCT CACC'ITTCCG TAAGCATTTC CGAAGCCAGA GGAGAAATGG TGCTAATGTC AGGAGGGAGA GTCCAGCAGC AGAAAGTCCA GCTACCAAGG GAATGTTGGA CTCAGTGGGA GCTAAGGAAG TAAGAGACGA AGAAAGGTCA 60 TGAGGAAGAA 'PTGATGTTAA AGTCTCTCCG TCCTGTCCCT TTGGCCTrT TTCTGTACAT TCATrACTAG GAGCAGAAGA GCTATCTAGT TI7AATACAAG AAGCAGAGAT GTGGCATrAC AGGCCMTGA GATCTGCTCC AAGCCACCTT1 TGAAGCTATT TCCACCATTG GCAGGCAGAA CTCTAACTTG CCAAGCTCGT TCACAATACC ACACCACACC T-fGGT7AATA AACACTGCAC TrGCMGCrC TCTTGCTCTC ACTCCCTC Fr GTrCCATT TCCCCTrCT CCTCTCCTCT CTCTGTCTCC TITCCAGT TGTCAGAATT CTACCCTITC CATCAACATG 65 CAAcT-rCTGT TYITCTCTA TCCCCATACA AC'VrAATATr CACAACTTFGT CAACCTGGGC GAAC'TCTG GTTTGGATAT AATGAATAGT TGA'ITACTGT AACAAGATAG CTCCCCC= T17'TCTn=AA TCACCAGACA WO 00/62736 PCT/USOO/08020 159 ACCACCATCA ATCAATGCAT CACCTFCACA GGTAGGTAGC AGGCCAGACC AGTGTCCTGT GGCTCCACAT GTCCGAGCTG CAGAGCCATT GAGCGTCCAT CCTTCAGGAC AGGCGAAC'IT GCACACAGTG CCAAACACGG GCTCCCCACT GCAGCTCATG TTGATCTrC CCGGAACTGC CAGGCTFGAA CATITACCA CTGCAAATGT TAGGTACACA GGCAGAGMT CAGAAAAATC TACTGGAAAA CTrCCAAAAC TTGCTTAAAA GTCAACAATG 5 AATGTAAAGT GTAAGCGCTA CTTAGTI=C AGCATGTAGG AAA117AGGAC CAAACCCCT TGGGGCAATC TAGGTTCAGA AACTTTATGA AGTATTTGAC CTGTACCCTA AAAAAGTCTG CACTCAATrC TACC'ITGGCA GGAAGGAACC TCTTCTGTCC ATTGTCCCTG AGATGTGCAC TCAAGT7GAG TITGATCCATG TAATrCAAAT CCCTCCTCAC AGCTGAAGGC ACAAGAGGAC 117GTAGGTGA ATI'CTCCAAT AGGGGAATGA GCACACCTCA CCAAACCCTT CGGGGGCTGG TGGACAGCAT CGCATCTCAC AGCTGGAACA CACGAGAGAG CAC'1TTAGAA 10 GTGYFGC ATCTCCAGCA ATACG'TrTCC CAAGGTAACC AAGT~rCCCAA GCTC'ITCAAT AGTTCTT= ATCTTAAAAT AAAATAAAAA CAAAGACTGT ACCTTCACAT GTGGGCTTCT CGTTGTCCCA CTCCCCTGTG GG3GCCACATT GGAGCCTTT GGATCCCTTC AACACAAAAC CCTGCTCACA GGAGAACTCA CAGCTGGACC CATAACGGAA ACTGCCAGAA GCACTAGGAA GACAATTCAT GTAGCCTCGC TCGGGGTTGG ACAAGGCTGT GCACTGGAAA GCTGAGACAT CAAAATGATG GTCAGAAAAT ATTGCAGTGG AACTAGAGAG TACTTGGCGT 15 TTGTTGAGTG AACCCAGTI'C ATTCAAGCAA CACTrGGAGA ACTGAAGATT cn7IATAA'r CCCTGGACAA ATGGGAAGAT GGCTGTGTI1T TCTrGAATT TCAGCCCCCT CACTGATCAT GGCACTAATT AAAAGACTAA TTAATCAGAA CATrAG'ITCC TGAGCACTGT TCTCTAACA CACAAAATAA ATrATGGTCC AAGGAAAGAT TT1CACGCAGT CTGAGGACAA CATATGGGTC ATGGATGT ATAGATGGTG CCAAAAAGAA AGAAAAGAAA GCACCCCTAT AAAATITGTC TGTITGCAG MTGG'rrrr GTGTTATGT TTGCTACTGG AAATCATTCT 20 GTGCTGGC117 TGGCTAGGAC AAGGCCAGTG CCTGATAGTA AAAACTG=T G'TI17CAATA TCCTTGCTCT CACM~AAAG TGAATTAAAA TTACTGCTT ATATATGCAT CAATACTATC TCTGTAGCTG ACACCATGCT TGAAACAGTC TCATCACTGC TAATTATGAG CCATTTCAGA AGACAGGTGT GATGAGAGTT1 TrACATTCAA ATCATGTTCT CATrA'rrCTG CTF7CCGAAT TTFCTAATAT GA~rCCTrA GATTAAGAAT TCTGTCTATT CCATGCTAAT GTCTACAAAG 'TTTATCAGC ACATCACAGT TAAAAAAAAA CAGCAAAGAA TTCATTCTTA 25 ACACATATGA TCC'TrTCCCT GGCCAAACAT TAGTTC=II AAATGAATCT CAAAGATACG AGGG ITGCTC ATCAAATCTG A'1TCTATAG 'ITAAAGTGGG TATTGGrrr TITTT7CACT GTCCAAG'lM GAAGATGGT GTTCTflTAAG AAAGTATAAA TCGAAGGATC TCAAGCTT1AC CTTCACAAAC TGGGATITGC TGTGTCCACT GCCCTTGAGT GGTGCATTrCA ACCTGGGCTG GTCCCTGCAA CATGAAGCCT TCCTCACAGG TGAAGTTGCA GGATGATTTG AAGGTGAACT CTCCAGCAGG GGAATGGCTG CACCTCACAG AGCCATTCTG AGGCTGGCGG 30 ACGGCCCTGC ATGTCACAGC TGTAACAAAT ATACGCATJG ATAITrAGCAC GGCCTAGAAT TAGCTTGCCC ATTCCAGTA TGGGTTGAGA GAAAGAATGT TCACAGTAAG TCTCCATGTG GAACAACTCT ACCTTACAC GTTGGCTTrCT CGTTGTCCCA ATTCCCAGAT GAGGTACACT GAAGGCTCTG GGCTCCCAI1 AGTITCAAATC CTTCT'TCACA GTCAAATGTA CAGGTrGTGT TCCATGGGAA GCI17CCAGGG TGGAAAC ATTCCACGAA CCCATTGGCT GGATGTCA CAGCATCACA CTCAACCACT GAGGATTrTA AAGAGCACCA TGAATTTTAC 35 AGAAGAATGA TC'ITrCACT TCCTATTGAG CTGGGTGCCT AACAGAGTGA GGAAGCTGCC TTCAAAGGGT AGATCCCAAA GTCCTATGTC AATTCTTAGG GACATGCACA GCCAGAATAA AAGCTITAT TCTITTTCAT GGATATTCTA TC'IICTGA TrrCCAC'1 GCCTATGCTG AGTGGTCTCT AATCTATG IT ATCATTTACG TGAGGTAAAA A ITTAAAAAA AATAGATrCC AGATTAGGAG ITATGACTAG TACTGACATA CGTAGGCTAT TCA1T1A=J TAGCCCATCA GAGCCTGAAG AACTGA'TI1 TCTTTT7G GCCTCTGG'IT CAGAAAGATA 40 AAATTAAGAG AGAAAAAGAG ATACTAAGAC TGCTTGACTA TCATGGTCTT AAGTTAGTCC CATGGC117GG AAAAGTTAAA CAGGGAAACA AGATGAGAAA TCCAY7GAGA TI1?CTAGAGC TATTGTT TATGGTCTCC CTTACAAATC ACCAGAGCCT CAGAAACACC CATrCAAGC ATAGAATAAA AAAACCTCTC TCAACCCAAG CAGGTACTGG GTTGGCAATA TACATrGGCT GAGAGAACAA ATTGTATTAA AAACAAAAAC AAAAAAAAAA C'TTCCCTGA AGTITIGAAA ATGTAAGTrG AATCAAAAAA CAGAAGCAAT GAGGGATGAG TTACAGAACG 45 TTCTGTGCAT TCTCAGAGGG ATrTACCATT GCAGGCTGGA ATAGGAGGAC TCCATTCTCC AGAGGACATA CACTGCATGG TCTCCATGCT GC ITGGCAGG TAACCCCTAT CACAGCTGAT AGAGCAGGAA GAATTGTAGC TGAAGTITCC CAGTGGGTGA CTGCAAACCA GGCTTCCATG CTCAGGGGAT TCCAGGGCTG TACAGTI1CAC AACTGAAAAA GAAACCCAAA TCAGTTCTGC TCATCTCTCA CC ITTAACAG ATAAGAACAC TGGAAACTAG AACTACAGTr TGGTTIT= 'TTTAGT 'FrAAAAAr ATAAAATTIC TAATGGAATT TGTAAAArrG 50 ACTGTAATTC TACCCCI1T CTIT-YCA AGAAAATGCT GATCCATAAC AACAACAACA AAAAAGCAGT GATGACAACC ATAAAAAAGA AATATTGAGT GATATGGGGA GAGTAGTGTA ATTGTGMrA CCTCAAAACT GTTCAAATTA TATGAACAAA CACAGCAAAC TTAGGTACCA CAACAAAI= CTrGTTACT-r TTCTCACAAC TGCTAAAAAT ACTACAGTAA GCTrCCAACC AGGATGAGAA CCATTCACAA AGCTATA=Y CAAMTI'AAG TACTAGAATA CATT1ACAAAT TTrAAAACCC TAATGCTGCA CTGTCTACTA TAGTAGCCAC TATCTGTGTG 55 GCTACTCAAA 'TrTAAACTTG AATTCGTTGA AATCAAATAA CA'TAAAAT TCAGTTCCTC AGTGTCACCA GCCACA ITTC AAGTACTCAA TAACCACATG TGGCTCATAG GTACACACTG GAAAACACAG CTATGGAACA IMCCA'rTAT CACAAAAGCT CTACTGCACA ACGCTGTGCT AAGGAATCTT GGAGAGAAGC TCATCTAACT CTCTTAATGT ACAAA'IMAG GAACTGAGAC CTCA'TTTCAT TCAAGTGACT TGCTCCATGC TACACGGCTA GTCATTACAG AGCCAGAGGC CAGAGCATGA ACCAAGATAC CCTGGACTCT GTAACTCACT CATCTACT 60 GCAACGTCTT GT-rACCACCT AGATGAGGTG AGTACATGTT CCTCGCAGGG ACACAGAATT1 ACAGTThFAT-r GAATGTGTCC TGTGTGCCAG GCACCATGTA ACCATGAGCC TATGAAGTTC ACACTATTAT TATCCTCATT TTACAATGAG AAAACTGACA TAGAGAGTTA AACTATCTTG TCAAGGTGCC AAAATAAATA ACTGGTGAAT CTAGGACTCA AACCCAGCAG GGTCTGAC'IT CATAGTCTCA GCTCACGATC ACCATATGAC ACCATCTGCA CCAGGGAAGG GAAGGCATGC AGACCTGACT CTAATGCCAG CTAGGACGTG AGATGGTGCT ACCATCTCAA 65 GTGAAGAAAG AGGCAAGAAC CAGA=TACT 'ITGCTCACAC TTGAGTCCAC TGAAGCCAGG GTCACACTITG CAAGTGTAAT TATTGATGGT CTCTACACAT TCACCGTGGC CACTGCAGGA TGTATTGGTA CAGGCAGCTA WO 00/62736 PCT/USOO/08020 160 CGGAAAATAC AAAGCATGAT GAGGAGGACT ATTACTGTGC TTATACTGAG TGCCTTTGAT TTTAGAATCA ACAGTGTGCA ACAGAGACAT CAGCAGTCCT ACAGAGTGCC ATAGACTTTA ACTGAAGTGT TTTACAAAGT TCCAAATCTG AGTTTCAGGC CCACCTATCC TAAACCTTGA TGCTAATGTA TAGCTGTGGC TGGCACCTAC CGTAGAAAAT TTACTTCTTC ACAAACTCTG AAGACAGTTC CCCTACCACA AATAAACAAG TAATTAAAAT 5 ATGTATTGTG TGTGTGCATT TTTATATGTA AAGAACTACA TATTTGCCTA CAGTATTTAT ATATATTTTA TATATATACA TACACACATA TATGTGTGTA TATGTGTGTA TGTATATATA TAAAATGTAT ATAAATGCTG TAGGCTATAT ATATATACAC ACACACATAT ATGTGTGTGT GTATATATGT GTGTGTGTGT ATATATATAC ATATCCACAT ATTCTTGCCC ACATTCACAC AAAACAGCAA AAGAGAGAAA CTTTAGCAGT TAAACAGAAT CTITTGGAAC ATAAAATGAC CACAATAGAG AGCAGTTTTT GCATGCTGTA AATTTGCCAA GATGCCCACA 10 CACTGAAACT ACCTCCCACT GCTGCCGCAA ACTCCCTACC TGTGTAGCAT AGGGCAAGCT TCTTCTTGCT GCACCTCTCA TCATTCCACA TGCCCACATC TTTTTCTCTC TTGATGTAGA TCTCCACGCA GTCCTCATCT TTTTGCCTAT TGTTGGGTTC ACCTGGAGCC CAGTTCTTGG CTTCTTCTGT CAGAGGTTTC TGGGTTCCTA CCCAGACCCA CACATTGTTG ACTTTTCTGA TTCCAATCCA GTAATAACTT GGTGAATAGC TCAATATGGA GTTTAGGTAC TCAATCTCTT CTTTGTTTTG AATTGCAACC AGGTGTGTGT ACCTTTGCTG ACAATAAGCA 15 CTGGCCTCAT CATAAGTCAT AGCTTCCGTG GAGGTGTTGT AAGACCAGGC TCCACTCTCT TTAATGAGAA GCACTAGTGG GAGAAAAAGA AAAGAAATGG TAGAGTTTGG TACTGTTGTG GTTTAACTCT GACAACTGTG CTTTTTATTG TCTTATT GGCAATGTTT GTGACATGGC CCAGACTTTT CTCATCTT CAAAAGTAAG AAGTACGTAT GAAGAAACAG CGACTTATTG TTTATCTCTT TTGTGACTGC CACCCACTAG GTACCTTATC CACACTCACT CACAACATTA TAGTATACCC ATTTTGTAGT AGAATAATAA TCAGAATAAC TAAGCTTAT 20 TGAGCACTTA GTATGCACCA AGAAGCACTG TATGAGGTAC TTCCATGAA CCATGCTATT GAATCCTCAC AATGCATCTG GGAAATAGGT CATTATGATC CACACTTTAC ACTTAAGGAA AGGGAGACAC CAAGAGGTAA AGTAAATGAC CCCAAGCCCA GGGAAGAACA CATTGCAGGT AGAGGTCAAG GATGCTGCCA GATATCCTGT GCAGGACAGC CCCAGACAAG CAAGGATATT TCAGTCTGAA ATATCTATAG TGCGAGAATG AGAAATCTTG GTCTAATGGC ACTGACTTAC CCAAAGTGAG AGCTGAGAGA AACTGTGAAG CAATCATGAC TTCAAGAGTT 25 CTTTTCACCC AAAGGTTTAG GCTTGAAATA CTTTCCTGGG GAGATAAAAC ACAAAATGAA TTAAAGAAGG AAATCGTGGG TAGCTAGTTA CATTATTCTA CCATGATGTT TAAGGCAGCA TCCTAAGATT TTGGGCAAAG GACACTAGTG CAATAATCTT TATCAGAG TTTAATCAAA TAAATAAACA AATTTTAAGA CTTTCATTAT TTAGGTCAAA GAGAAAAGAC AGGTTTTAGC TACAATACAA TAAGAGCTTG TACAGATGTG GTTTTTATTA GAAGGCCTTT TGCATATCTG TGTTTCATGG CCCGAGGCTG CCCTTATAAA GCGTTCTGCA CTTACCGTTT 30 TGGGAAGCAG TTGTTCAAAC ACAGGATCTC TCAGGTGGGT ATCACTGCTG CCTCTGTCTC AGGTCAGTAT AGGAGTTTTG ATGTGAAGTC AGCCAAGAAC AGCTGAACAC TACTTCGGCT GAGGCCCTTT TATAGGAGGG ATTGCTrCCT GTGAATAATA GGAGGATATT GTCCACATCC AGTAAAGAGG AAATCCCCAA TGGCATCCAA AAACTTTCCC GGGAATATCC ACGATGCTTA AAATTACAAT GATGTCAGAA ACTCTGTCTC TTGAAGCTAC TTCACCTTTG TCCATGCCTT TATATCGTAT ATGCAATTTT ATTAATATGA CAAAAATGCA TGATTTTTAA 35 TTATAATAAC ATAAAGTCTA TGTCTTTAAA AAGTTGTAAA ACTTGCTTG TTAGTAGTGT CTCTCATGTA GTTGTGGTAG TAATTAGAAT TTCAGAAACA GAAGGAAACC AAGAATAGGT TTGTCATCCA TAGTCTACTA CCTTCAATTT CTCATTCATA GCTGTGGATA ACCAATCACT ACTCATTT TCTTCCTTTT TCACCTGCCA ATTCAACATA TTTAACATGC ACTGTCTCAC AGAGGAATGA CTCACAAGGT AGATATTAAT CTTCAGATTT TGCACGGCAG TTATGCCTAA ATTAAAATAT TATCTAAAAA TAATATCTAA CACTCAAATG GTTAAAATAA 40 TGCCTTATTT TAAAAAAAGA AAAATGGGAA ATAGATATTT ACATCTGGGA AAGTTTCATG GTTTGTTCAG TGAAAAAAAT AAAAAGGAGG CCAGGCACAG TGGCTCACGC CTGTAATCCC ACCACTTTGG GAGGCCGAGG CAGGCGGATC ACCTGAGGCC GGGAGTTCAA GACCAGCCTG ACCAACATGG AGAAACGCCA TCTCTACTAA AAATACAAAA TTAGCTGGGC ATGGTGGCGC ATGCCTGTAA TCCCAGCTAC TCGGGAGGCT GAGGCAGGAG AATCGCTTGA ACCCGGGAAG TGGAGGTTGC AGTGAGCCAA GATCACGCCA GTGCACTCCA GCCTGGGAAA 45 CGAGTGAAAC TCTGTCTTAA AAAAAAAAAA AAAAAAAGAA AAGAAAAGAA AAAAAATAAA ACGGAAAACT ATATATATAT ATTTAATTGG TCAAAATTTT GTTTAAAATT TTTGAAATGT TAATGTGCAA AGAATAAAAA T TCTTCCACA ATGTTAACAG TGACTAACTC TGGATGGCAG GATTTGGGAT AATTTTTATA TCCTTCATTA TrATTTTCAG GATTTTAAAG TITTTTCAA 1TTCCCTTTT TTTCACCTTT ATAGTAACAA GAATACAGTT TAAAGAAACT TGTCTCTAGG CCAGGCATGA TGGCTCATGC CTGTAATCCC AGCACTTTGG GAGGCTGAGG 50 TGGGTGGATC ACCTGAGGTC AGGAGTTCCA GACCAGCGTG GCCAATATGG TGAAACCCTG TCTCTACTAA AAATACAAAA ATTAGCCGGG GTGTAGTGGC GCATGCCTGT AATCCCAGCT ACTGGGGAGC CTGATGCAAG AGAATCGCTT GAACCCAGGA GGCAGAGGTT GCAGTGAGCT GAAATCACAC CATTGCACTC CAGCCTGGGC GACAGAGCAA GACTCCATCT CAAAAAAAAA GAAAAAAAGA AAAAGAAAAG AAAAGAAATT TGTTTCCAAA TGCAACAGAA GGAGATGTAT GTGGTATCCT ATATTCCTGC TCTTCATTTT GACATTTCTT CTGGGTGATT 55 GTATACATTC CCCATCTCTG CATCTTACCC TATCTAAATG ATGGTAACAG TAAATGGGGA TCATTTTAAT 17CCATATTC TGTAGGTTTT CAGAGCTCAA GTCAAGCTAA TATTCTATAT CTACAGCCTT TCAAAATAGG AGGTCTATCT AAAAATGTAC TGTCAGCAGA CCTGAACGAG TAGTGGTAAA AGCCTCGTTT TTCTCTTTAC TTGTTAGCAC TGGTCTTTCT GTGTTCATAA AGATGTCAAG ACCCAAAAAA AAAACAAGAA AAGAGAAGAA AAATTCCAAA AAAGACAACT GATTAGAAAA AAATAACTTA ATTAACGAAT TTAATTCAAC CCCTATCAAA 60 AAGCATAGAA TTTATTCCCT CCACCTTACC ACTCTCTTAC ATGATCCAGA TACTGACATT ATTCCAATTC TTTATCCCAC TTTACTTAGC TCAATGTGGT TGTTGCTTCA ATAAATTCAG AAGAGTAATC ACTCATATAG TGTTTATTTA GATTTTAGGG CAGAATGTCA AGTTGGGTTA ATACATTATC TGTATGTATT TTATTTTTAA TAAAGTATGA ATACATAATC TGCTATTTTT AAAAAGCATG GTCAAATGTA TAGAGTAGCC AAATCTTAAA AAACAATTTA TCTTCGATAT CAATAAAGTA CCTAATAATT ATATTGCTAA TAGAAATTAG TCGTTAACAT 65 CCCTAGATAA CTAACTTTAT TATTGCGAAT TITTCATAAC TAAGTTTATA GTTTATCTCT TCCCCTTTTT AAAATTAGTT CAAAGATATC TAAAAATAGC CCCAGTGGTG ATGAAGTTTC TATTTTACTT ACATATATAT WO 00/62736 PCT/USOO/08020 161 GTCCTGGACC CCCAATTATA ATCTCTAACA TTTATrGAGT GCTACTATG TGCCAGGCCA TATrCTGAGC ArTrGTATG TWCACCTATT GATTATTCAA TCCGTACAAC AGCCTATGAA ATAGGTACTC CTATTATCCC CAT=TACAG ATGAGGAAAT TGAGAATCTG GGGATITTAT CTCA'ITCAAA AGCACAGAGC TAAGGGTTrGA AACCAGGCAG TT1GATATCCA GAGCCCACTC CC'ITACCTGC TACTCCAAAC CATGATTrCT TTTGTrGTTA 5 TGCCCCGAGA TTCCTGT7C TACCCAAGTr TCCTGTACTC TT~GCCCT CTrCTTCCTG AGACATCCTT GACCATCACA GCTCTCCACT GAGATAACTG TGTCCTGGGT TCTGAGACAT GGGGGCTGGA AGGGACCCCA GGGACAGTGA GCAGTAGGGA GAGGATGCAG TGAGAACAGA CCCTGGATCC CCGGTGCATA GGCAGGGAGA AAGTGGACAA AGGAAAAAAC AAGCAAGGCA GGTGGAGCCA TGCCTAGGTA AAGTTGATCC CTAAGCCACA GTTCCCAGAA GTTCCTGATI' CAAAAGCAAA YI=CTCTAA GGTCAAAGGG CAAACTGATr ATTCTAAATrT 10 CTAAACTGAT TAITICTAAA TTGAGAAAGC TTCAGGGAGA GATCCCAATA TTCGAAGGAT AAGAGAAATG AGGAGTGGAA GAGATAGGTG AGTAACAGTA ACTTAAATGT AGACTATATA TAATATATAA TATATGTAGA GTATATATAT ATAATT1ACAA TATATTATAT ATGTGGAATA TATATATTAT TTATATATAT TTATATA'TTT TATATATATA GATATTA TA'IT1ATAT ATAAATATAG ATATITIAT ATI=ATATA TAAATATAGA TATTITATA TATATTATAT ATAAATATAT GTAAAATACT GTGAAAGAAG AATAGAATCT TGAGACCTCA 15 AA11TCACTAT GCCAAAGGGA AAG117AAGCT TGGGAAATGA GTCATGCAAA AACTGCCYTC CTTITGTITCC CAAATACCTG TAATTTCACA TGCTTACTIT ATCTTATATA AAATGTAGAT GTACTGAGCA TGAGATCCAT GCATAATTTC CCTCTAGTCC CTTCTI1A CATGTAAAGT GTAGACTCAC TGAGTGTTAC AGAGCCTITGC CACAATGTAA ACACYTGTCT CATrGCCAAC CCATCTTrCG TTATITCT TCCCCTCCTG CY-FGCTCT CCCCTCTAAA GATGGAAG'IT CCCAAAACTC TCT1TTGGAAA AAGCGCAGGT CACAGATCCT ACAGTGAT 20 GTGTrCT' TACCTGGGAC AAAATAAACC TCTAATCTGT TGAGATATGC TTCAGTTACT TTTTGG'TrTA CAATATGTAC ATGTATGTAT ATAMTTTATA TGTATATAAT ATATGTAC117 GTITAACCA GAGGTATGTT ATTrCAAAATC CATTCATCCT TACAAT7ACC TGCATI'CTCC CACAGTA TT TCTGTGTCCC TGCCCCCGAG GTTGTCACTG CAAATCAGGT ACATGGATAC TGGGAGCTGA TGGGCTCCCC TCTGGCTACC TGGGCTGCTG AAGGGGCCAT AGACAGACCC AGC'T1CCTC TCGTGGAGAG GCCCTGGGCC AGCGCTGCGT GGGAGTGGGA 25 TTACAACCAG ACTATAGC'IT CTTCACCTGC TI1TCCTAT CAGGAT7CA TAAGAGGCAA ~TTG1TTG '1TTGAGGGTG GGGGCAAATC AGGGGGAGTI' GAAGAGGAAA TTGGGTAAGA TTTGAATAGT TGGGCATGTF GAATATTATG AATATCATCT CCCTCTrCAA ATAATCCAAA ATATACCCCC AAGAAACAGG CTGATTAGAG GTGCTTCAAG GCTCCACTGA ATCTCCCAAG CTCTGAAGAT GTAGCTAGCT GTTACCGGAT TGCCGGTVI1? CAAGCCTCGC CTCACATGGA CCCTCTrGGC AGTTTCTCGC ATGGGGGAAG CATCCGCTAC ATAGATGGGA 30 ATGAAAAGAG GAAAGAAGAC GGTGCAAACT CAGGCACACC CCGGTGTCTG CCACCAGTGC TAT~rAATCT CTGAGGTGTC ACCCTrCCTG GC'=ATTGT CTC117CCTGG AAGTCTCTTG TCCTCTCCTC CACACCCTTT AATCAGGCAT CAAAGAC'T AACCAGTT GCTGTGTGCC CAGGCCCACT CA'ITCTCACT YT-ATGGCAA AGGGAGTGGG AGACAGAGAG ATAGCCAGAA AGAAGAGATT GGGGACCCCA AGACAAATGT TAGAA'TTrA ACCAAGGCCA CCCTGTGGAC AGGAGATTAT TGGG'ITAGT GGAAAGCAGC ACTGGCCACA ACCACACGTG 35 GCAAAAGCAT CTATCGAGGA GTGAAGTT1AT ATITGGTGAA TGTGACCGGG AAGCAGGGGC AGTGGTGTCC TCCTGCCTTC CTGAGGCACT CTGTTCCCTT ACCTCTGCGA AGGCTrA2TT TACCCCTGAG TGCTITAGTT TGAAAGCCTV AGTCCCTCT CTCCCATAAA AAAGCTCTAC TCTGCTAACA TCTAAG'ITAC C=IIGCAGAG TC'FrAGGTAG AGGGAGGAAA TCCCAATAAA GA317CCACCC TATCTGCAAA ATACAAACAT GGTATTTCTT GCATTCCCAA AATTGTGAAA GAAAATGTGT ATCACCACAG TAGAGAATGG CATITI1GT TrGATCAAAA 40 CCTAAATATA TGATGAAA ATGTGTCTGG TTCTAAG'rrr ATTTCCCAGA AAGCCATGTT TACTCACTTG GAA'rTrATAG ACATCTT1ATA ATATCTGAGT CGAGTAGGAG CTCCGGGCTC TACCTCACTC TTrrCTCCCA CACCCAGGGG GAAGTGTAGG G317CTCAGAC TTTAGAATAA AGAGGAATCA CCTGGACAAC TCACCTAAAA TGCACATC317 CAGGTCTCAT ACTCAGAGGC TCTGACTCAA CAGGTCTGGG TGGCGCCCAA GAA'1TTGGGC TIT7AAATGAG TATCTCAGAT GATTCTAATA CAGAATGTGT AAGATGACCA GATCCTATCA CACTTAGATG 45 TATTGGCCTA GGGCCACCTA AC'ITGGAGAA AATGTTAGTA AGACCCCGTG GTT1GGTGCTC AGCTATAGGT ACCAGAA'ITT TGATCAAAAT TTACTATCAT TGTGACACTT CTCTTCGGAA CTGGAAGGCC AGAACCCCAC 'rrGTAAAGTG CTGGGAAAAT ACAAGGAAAA TTAGGGTGA GTAGCATITI GAATTCTTAC ACATGGAAAG TAAATGTATA AGAATTCTTA CCAATAAAAA AAAAGCAAGA GAGAATAGCT GCTAAAGAAT TAACACAAAT ATGTATATAT TAG'ITA317CT CTFTICTCCT CTGATTCCAG AGGACTITGT AATTCCACTA ATT=CTJG 50 AGCTTCCAGG ATGATCTGAG AC'FrGAATTT TTCATGTGCT TITGCT7CC TATGGCAG CATCTI7ATCT TGAAGITCC GC'ITTCTGCT TGGGGACCTA AAAACTAACT AATGGGAATI' TCTTCAAAAT GAGCAAACTC TGGTGAATTC CCAAAGCGGA AGAAACAAGT GAGGATCGGG CTGGTTAATT AAGAGAAC1T TTCCTGAATG TAGCCAGACT GT117GCCGAC TGYFGTTAAC ATGAGGGAAG AAATACCCCT GGATMAGA AGAGCCCCI1 GTTTGT'C CITrGGCCATT TGTGCTGCTr GTTTTGTAAG TCAGAAATTT CCTGAAGGAC TATTAFrAGC 55 mT-GrCTCA CGTCAGAAAA CTI'CTGCTCT GGCCAC TI' AAACATATAA CTTGGAT=f ACTGTATTAG AAAATGTAAC AATTACAGAC AGCACTAAAA GGACACCAAA GGGCAAAGAA AATGGGTAAC 'TTTrCT TCCCCAAATC TAAAATAGGT GATITGGAG AAGTAGGAGA AAAACCTGGA TITCTAGAT CTCTTTAGAG CTCAACAACT GATATAGTA ATlATGTAAG TCTTI'GATAT T1'GGAAATGA T7GGATI'AAC CGGATAACAA TGAATATTI7A AATACAGTGA T17GGCCAGG AGCAGTGGCT CATGCCTGTA ATCCCAGCAT TTGGGGAGGC 60 TGAGGCGGGT GGATCACCTA AGGCCGGGAG TTCCAGACCA GCCTGGCCAA CATGGTGAAA CCCCATCTCT ACTAAAAATA CAAAATTAGC CAGGCGTGGT GGTGCAAGAC TGTAATCCCA GCAACTCGGG AGGCTGAGGC AGGAGAATTG CT7GAACCCG GGAGGCAGAG GTTGCAGTGA GCCAAGATCA CGCCATTGCA CTCCAGCCTG GGCAACAAGA GCGAAATTCC ATCTCAATAA ATAAATAAAT AAATACAGTG AITTTAACACA AGAGAT7CT ATTTCACACT AATGAGCTCT GTCACTGGGG CAAGCTTC'IT TGCCTCATTA AGTCTCAGAT 117CCCGAGAG 65 CTTA = ArT TATACCAAGA GTG='~ACT ACCGTCTCTG CTAGCTGTGA CATAATATGA CAAAAGGTAT AAATATGGGA AAAGGCACTA AY11TATATCA AAGCGTTCTr CG TICCT TGCTGTGAAG 'TrrAGCTA WO 00/62736 PCT/USOO/08020 162 ATAATTCATA AGAATATACC ATA TrAGAG TG'TrACTAT GCATGGGCCT GGCACTTCAC ATACATTGCT TCTTACAAAT 'rITACAAAGT GAAAGGTAGA TAUFAATCTC ATTATGGA GGACAAGATA GAGATCTGGA GAGGTTACAT AACTTGCCAG TGTTTTCA GT7AATAAAT GGTAGGGTGG AGATrCAATC TGTGTTACTC TAAAGTCCGT GTCCWTTA TTGGCTCCAT GCCTACTCAG A = AAATCT CAGCAGGGAA GTAAACCT7A 5 GTTTACAT GAGAAAATGT TACAGCAGCC TTCTCGGC'F CC'1TACCCC CATCCCAGTT TCACGAGC'r AGTGCCTTAG ATCGGGTT1CC 'TTTAGAAGCA GACCTCGAAA TAAGGATGTG GGTGCCAGTC A'IMATrGAA AAGATGATCC CAAGAAAGCC TAGTAGGAGA GTGAGGAAGT GAGATGGGGA AAGGAAGAAA CTCCACAAGA AGTGTGTTAA TAAGCAGGTT ACCGCTGTGG GCAGCCATGG GGCTCAGCTG CACTAACAAA CTCTGTCTAG TACAGAAAAC CTCAGGGTCT CCCCAAGGAG GGGCAAGAAG TCTGCCTAGG GTATATATCC GCCAACTCAG 10 TCACTGGCTG AGAGCTGATC CTGGGAGGGC ATGGTrAATT CCTCTGCACT TTCAAGTGGA TTCCTGTGGT CAGAAAAAGC CCTCTACAAT GAAT7CCAGA TGC=GTA'rr TAAATCTGAC ATGATCTGAA TGCTGTGTITG GGACAGGGTG GGCcYTrA'rA GTITICTGTC ATTACTGTAA CAGATTACTA CAAACCTGAT GGCTGCAAAC AACACATATT TATTATGTCA TAGTTTGTGT GGGTCAGAAG TACAGGTTAG CTCAACTAGT 'I1CTCTGCTC TAGGTI17CAC ATTGCCAATA TCAAGGTGTC ATCCAGTrGG GCTCTTCTTG GGAGGCTTGG GGATGAATCC 15 ACTITCAAGC TCATTCAGAT TGTTGGCAGA ATCCAGTTCC TTGTGG'FrGC AGGACCAAGG TCCCTGrrFGC =TGCTGGCT GTTGGCCAGG AGTCATTCTT AGCTCTAGA GACTACCTGT ACTCTCTGAC TCGTGTCTCC AC I1CACCTT TCAAACCAGC AGCGGCTAGT CGAGTCCCTC TCTTCAAATG TCTCCAACTG TGCCTTCACC TCATI'CTCC TCTGTGTACC ATGTCTGCCT CTACTGCTTG TAAGGGCTCA TGGGAT~rACA TFGGATITAT TCAATCCAGG ATAATCTCCA TATITTAAGG CTAGCTGACT AGTGATCTTA ATTCCATCTA CAAAGTCCCT 20 TCCAATAGTA CTGTA'PrAGT CCATITTCAT GCTACTGATA AAGACATACC CAAGACTGGG CAATTCACAA AAGAAAGAGG 'ITAATIAGA 'TrTACAGTTC CACATGGCTG GGGAAGCCTC ACAATCATGG CAGAAGTCAA GGAAGAGCAA GTCATGTC'IT ACATAGATGG CAGCAGGCAA AGAGAGAGAG CTTGTGCAGG GAACTCCTCT 'TrTAAAACC ATCAGATCTC ATAATACTT1A TTCACTATCA CAAGAACAGC ATGGGAAAGT CTTGCCCCCA TGATTCAATT1 ACTCCCACCA GGTCCCTCCC ACAACATGCA GGAATTCAAG ATGAGA=rG TGTGGGGACA 25 CAGCCAAACC ATATCAAGTA CCTAGATTCA TGTGATTA AACAACCAGG GAGCAGAAAT CTTCAGGAGT GGGGGGCATC 'TrAGAATI1C TGCCCACCAA GGCTGGGCGC GGTGGCTCAC ACCTGTAATC CCAGCACTTT GGGAGGCCAA GGTGGGTGGA TCATGAGGTC AAGAGATCGA GACCACCCTG GCCATGGTGA AACCCCA=T CTACTAAAAA TACAAAAATT AGCCAGGTAT GGTGGTGGGC ACCTGTAGTC CCAGCTACTC AGGAGGCTGA GGTAGGAGAA TCACTTGAAC CCAGGAAGCG GAGG17GCAG TGAGCCAAGA TrGCGCCGCT GCACTCCAGC 30 CTGGGAGACA GAGCAAGACT GTCTCAAAAA AAAAGAATTC TGCCCATCAT AGTAGGCTGT CCTACAGAGA CATAACCCAG GAATTAGGTG AATGGCTAAC CTAAATTAGC ACTGTGATGT GT=TCTGAC TTGGTCCTTA TAGCTCCTCT GCTTAGATGT GGAACTAATC CATGAATGCA AGGG'ITGTC TAGAGTI1A AGTGGGAGT AAATATCCAA AGTACAGGAG ATATTATGGG TGCCTCATCC ATGTCCC=T GGCAYTTATC 'TTT=GGAT AACCCAACTC TATTAGTIT TATATCTCAC 'I1GTrCCTAT ACTCTGTGAA CTGATGTCCC ATAAATAGAC 35 ATTTCATrf GCCAGTCTTrC 'YfGAACAATA ATTACGATA TTAATCTAGC AGTrATCA'rr AA F7GGCCAC TTCACATTAG ACACAGCACT TAGGAC ITAA GAATACCATG TCATFTTGATC ATCATAATAT GGTCAGGAAT TAAGTATTGC TATCCAAATI' TTACAAAGAA GGCACTGAGG GTI'AGAGT1 AAATAACTrG CTTAAGATGT CATAGCCTGT AAGTGACAAA ACTAGGACTC AAATACAGGT CCATCTGACT CCAAAGTCTA TGTTCT~rGGC TACCACACTG CCTCTCCTAC AAGTGACCTG TGGTITACT ACTATAT7CA CACTCTACTA ACiTrACCAT 40 CTCCCATGAG TCTGTCTAGA GGAGGGCACA CACAGCACAG AAAACACATG AATGCAAAAT AAGGAAGGGC CTACTTACTA CACAGAGCCA TTCTAATACC TGATG'ITTGC TCTAATCCAG 'm1ACTATr AA'I7AG'I1GC TGGTGCCCAA GTITACTG AGAAATGGGG ATAATITGG AAGTCATAAT GATGCCTTCT TCTCATAGGG TATTATTrT G'ITG'I1GTAT CTCCAGGCCC CAACACAGCC TGGCTITAG TAAATGATCA AAAATACCTG FTGAATGAAT AAATGGAGTC ACCTGAAACA TGTFAAACAT TTGTrCATGT GTCCTAATCG TGGATITCAG 45 GATAGTAAGC ATCCTAAAAG GAAAGCATGC ACACTGYI7CT TGCTACATTA ATTCTCACA ATATAAAAAA AGAAAAGCAT CTGAAAAAAG CTGCCAGCCG CTGTGTCTCC TAATATCAAA CTGAGCACAG ATATGGAGAA GCTAAGGGAG AGGGATGATG GGCCATGCCT CTAACCTCAT CATGGCAAAA GTCCTGGGGG TCAGACCCGA GGAGAGCAGG AAGTGTC IT TGAGGGATAC AMTCCACAG TGGAAATAAT GAGACTTFAAA TAAATATTAT ATACACAGYJ' CAACTGTTTT TATGTGTAAA GGTAGTAGGT TTCACAGTA AGGAAGCACT TC'rrrrr'I 50 TrTGThrGAG ACAGAGTCTC GCTCTGTCTC CCAGCCTGGA GTACAGTGGT GCTATCTCGG CTCACTGCAA TCTCTGCCTC CTGGA I1CAA GTGATrCTCC TGCCTCAGCC TCCCGAGTAG CTGGGACAAC AGGTGTGTGC CAITACACCT GGCTAATM7 TGTA TITA GCAGAGATGC GGTICACCA TGT7GGCCAG GCTGATCTCG AACTCCTGAC CTCAGGTGTT CTGCCCGCCT CTGCCTCCCA ATGTGCTGGG ATTACAGGCA TGAGCCACTG CACTCACCAA GCACTTCTAC TGATAGCATT TACAAACCCT TCTTAGAATA ITTAAAAATT CTAAGAGAAG 55 AGTAAATTGA GCCTCCCAA CTAATACTAG GAGGTTATAA CCTFCATACC AAAACTGGAC AATGCT7GCA CAAAAGAAGG AAGCCAATGA GGCCACCTAG AAGGAAGACT GGGCATTGGG CCCAGTGAGT CCTGGAAACC TCATCTGTGC CAGCCACCCC GGCATGGCCT GTATGAGTGG ATGAGGGTGA CTTGTCCACA GACAATAGCC ATCTAGCTGT GATAAAGGAG TCAAGGTAGT CAGCTGCATC TC'TrCACCT GTI'GCCAAT G'rTACACAGG TrGAAAAGCT AAGGTTTATG TAAAGCAAGC ATCAAAGATG ATGAAATGAT CAACCTGACA ATGAGTACTA 60 TGCTGCATTG TCCAGAAAGG AACTGTGGAA GATITGGGC TGANTCAA AACAGAATr CCTCACTCTC TGGATG'ITGG CTrACTTGGC C'ITTGATG'IT CAGAGGTGGT GCC'TTFGTGT TGTTGAACAA TG FrGATI= GGAGAGAAAA CAGAGYI'GAA AAACCCACAA GTCA'TCCCT GGGGAGTATI' ACCGGAATAC AGAGGATAAT TTCAGCAAGC CAGCAAGGCC TCATCTCTGC TT1CTAATAGA TAGGAAGAAA GGAAGAGAGG AACAATACT TrTAAGAAG CTCAGC'ITTA TCGCCTI1ATC TCATAGAAAG ATGCCTCCAG TCTGTCTGGC TAAAGGTAAT 65 TGGCATGGGA AAGTC'=AT CTGTGATI'CT AACAAGTGGA ATGTI1CCCT TCATTAAGAG AGCCTrGTCT GGCT'TGGGGA AATGAAACAC 'TrCTCCGAT ATGAGTGGGC TGTAACCCCT GCTACTAAAT ACTCAGAAGA WO 00/62736 PCT/USOO/08020 163 AATAAGGCGG TrGTGGAGCA GTCAGGAATG AGTCACTTGC CTCCCTGGAA TA'ITCAGAAA ACTGAATCAA AAGTACATTC TTCTGGG1T1 TCTrAGTCTA ATAGACTAAG GGTCTCTACT TFlGTTAAAFT TCTGGGAAAC AGCATAGAAT GGGAGAAAAA ACTGGTCACT GTAGTCATGC AAATCTGCAA AACAAACAAA AAAGTCTGGG TATTGCTGCT AACTAGCTAT GTGACCYI'AA GCAAGGTATT AACTCTCTCT GAATTrCAGG TTCTTCATCT 5 GTrAAATAGC ATATCTGTAA AATGGGAATT ArTrCATAT CATAATGCTG TAGCITTTAAA AAATAAAATA AAATGGATGA GATAATCAGA ATTAAAGAGC CTGGGATATA TAGTTAATAT ATAGGAGGAT GTAAAGATCC TGTTAGAAAT GCTAATVI17A CAGWrAACCA 'ITTGGAGATG ATCCGCCAAA GCTGCTAGTG TAGAGGCAAC TGAGAAThrG CCTGTCCTTC AGAATATGAA TAAATAACTG TCAATGATGT CTCAAGCCTA GAAAAACCTA TCCATCTGGA TGGGTGGGAA A M CTAGGC TAGTATTGAG AAGCCCA'IM CTrGGGAAAT AGGTCCTGGA 10 CTGAGTGAAG GAAAAGAAAC AGTAAAACCC ATGGTAAAGC AGCAAGGCTC TCTAGAGGCT CTGGAGAGGA TGAATTGAAT TCTAGAAGAT GAAGTAGGGA AGACGCTTTA CCTTCITGTG AAATGGA'frC AAAGA'ITCAA AGACCI17CGG GAATCTCCAA TI7GTATAAAT GGCACCATAG CTGTATGTTC CATGGAACAC TACTTCCCAG AGATGCCCAG TGAAAAAAGA ATGCCACAGT CAAATAAGTT TGGAAACACT 4CCA'ITATGTG GCCACCTCCT TGAAGACTCT AATGCACATT AGCATGTTAA ACAGTCTTGA GAAGTCCTGC AGAGCAGAAA TTGCrTCACA 15 TCTGCTAAGC CGGCAGTTTC CCAATATACT TGATTATGGA TAGTITIC =TACAACAC CATTCTCTGA TATGCTTCCA ATGACATGAA ATAAATATAT ATGCATGAGG TTC'rrCATrA GGGCATACTT1 YPTAATAGAA AATATTGAGA ATAATCTAAA TATAAATGCA CAGCA TTTAC CTTrCTGCA TAAACTATAT ACAGGCATAC CTTGGAGATA CTATGGGTTT GGTTCCCACA ATATCTCCAA AACCACATI'C GGTnTATGA CCACTGCCAT AAAACCAGCC ACATGAATTT TTTGG'ITTCC CAATGTATAT CAAAGTTACA 'TTrACTAT ACCATAGTCT 20 ATTATATATA CAATAGCATT ATATCTAAAA AACAACGTAA ACACCTFAAT TTAAGGCTGT GGCTGG'ITG ATI=CTACC CAGACCACTA AAACNTT CATATCAGCA ATAAGGCTGT TFCAC1CT TACTAThTI'T TGTGATAGCA CTTCCTTT CC117CAAGAA T T=~CCTr CTATTCACAA TTTG1TTTGAT ACAAGAGGAC TAGATTAG CT-FATCTCAG TTTAAGGTGT FrACATGTT AGCTAAAAAT GCTAATGATC ATCTGAGACT TCAGCAAGTC ATAATCTIT GCTGGTGGAA GGTCTTGCCT CAGTGTlGAT GTCTGCTGAC TGGGTGGCT 25 TGGCAATTTC TTAAAGTAAG ACAACAATCA AGTIGACAT ATCAATTGAC ccT-rCCTGTC ATAAATGATT TITTTCT CTGTAGCCTG CAATGCTCTT TGATAGCATT 'ITACCCACAG TAGAATITC AAAATTGGAG TCAATCCTTT CAAACTCTGG TGCTGTITA TCAACTAAGT TTATGGAGTA 'rrAGAAATCC CTTGTTGTCA TTTCAACAAT GTTCACACCA TCTTCCCCAG GAGTATATTC TACCTCAAGA AACCACTrC TTTGCTCATC TATAAGAAGC AGCTCCTCAT CCACTAAAGT 'ITATCCTGA GATTGCAACA ATrCAG VTAC ATCTTCAGGC 30 TCTAC'ITCTA ATTCTAGPrC TCTTGCTGT TCTATCTCAT TTGTGCTrrAC T7CTCCGCT GAAGTC'rTGA ACCCCTTAAA GTCACTCATG AGGGTTGGAA TCAACTTC'IT ACAAACTCCT GTTGATGTTG ATAIrTGAC CTGCTCCCAT GATrCATGGG TATTCTTAAT GGCATCTAGA ATGGTGAACG 1TICAGAAG GTITCAGTT GGCTTGCCC GGATCCATCA GACGAATCCC TATCTATGGA AGCTATAGAT TTATAAAATG TA'TTCTT= TTTGTGGGGG CATAGCGTCT CACCCTGTCA CCCAACCTGG AATGCAGTGG CACAGTCATA ACTCACTGAA 35 GACTCAAACT CCTGGGCTCA AGTGA ICI1 CCACCTTGGC CTCCCAAAAC ACTGGATTAC AAGCTTGAGC CACTGTGTCT AGCCCAAAAT GTATATCATA ACTAATGAGG CTrGAAAGTC AAAGTGACTC CYTGATCCAT GGGCTACAGA ATGGACGCTG GGTTACCAGA CATGAAAACA ATACTCATCT CCTCATACAT CTCCTTCAGA GCTCCTGGGT GAGCAGGCCC ATTGTCAAAT GAGCAGTAGT ATCTTGAAAG AAA'TTT TCTGAGCAGT AGATCTCCAC AGTGGACTTA AAATAGTCAG TAAACTATGC TGTAAACAGA AGTGCTGTCA TCCAAGCTCT 40 GThTI'CCAC TGATAGGGCA AAAGCAGAGT AGATTTGGCA TAA'I1CTCTA GGGCCTTAGG ATTTTGGAA TGGCAAA'I1G AGCATTGGCT TCAACTI TT fTTITIT TITI"ITrGAG ACAGAGTCTT GGTCTGTCAC CCAGGCTGGA GTGCAGTGGT GCAATCTCGG CCCACTGCAA GCTCrGCCTC CTAGG FJCAC ACCATI7CTCC TGCCTCTGCC TCCTGAGTAG CTGGGACTAC AGGCACCCGC CACCATGCCC GGCTAA'IlTr TTGTAT=TA GTACAGACGG GGTTCGCCA TGflAGCCAG GATGGTCTCG ATCTCCTGAC CTCGTGATCC ACCCGCCTCG 45 GCCTCCCAAA GTGCTGGGAT TACAGGCGTG AGCCACAGCG CCCAGCCTGT CT~rCAACT~rA AAGTCGCCAG CTGTGTTAGC CTCTAATAAG AGAGTCTGCC TGTCCITTCA AGCTGAAG CCAGGCATCA TTCTCTTCTC TAGCTATGAA AATCTTAGAT AGCATCTTCT CCCAATAGGA AGCCATIT TATGCCCTAA AAATCTGTCG M~GGTGTAG CCACC'FrCAT CATTGATCTT ACCTAGATCC GCTGGATAAC TTACCACAGT GTCTACATCA TTACTTCTGC TTCACCTTGC ACTI=ATGT TATGGGGATG GCTCCTTCC TCTAACCTCA TAAACTAACC 50 TCCACTAGCC TCACA'rTCrr C1TIACAGC TTCCTCGCCT CTCTCAGAGT TCACAGAATI' GAAGAATGTT GGGCCTTGGA TrACACTTTG G TrAAGGGA ATGCTGTGGC TGGTITGATr TTCTATCCAG AACACTAAAA C'TrCTrCAT ATCAGCAATA AGACTGTFC ACTI1TCL1AC TATTPGT GATAGCACTT TTCC'I11CCT TCAAGAA'IT TTFCCT[CTA TTCACAAT'17 GACCGTGA TATGAGAGGC CTAGATITA GCCAATCTCA GTITTACACCA TGCC TITTC ACTAAGCT]?C ATCA11TAG C'TITA'IM AAAGTAAGAT GTGTGACCCT 55 TCC =CA'rr TGAACACTTA CATGATGATG CCTGGCTrCA AAGC31TGAAA GGACAGGCAG ACTCTC'I1AT TAGGGGCTAA CACAGCTGGC GACT1TAAG TI'GAAGCCAA TGCTCAA'ITr GCCATTAGAA GCCATTGTAG GGTTAATTAA TTTGCCTAAT 'TrTAATATrA TGGTGTCTCA GGGAATAAGG AGGCCTGAGT AGAGGGAGGG AGATGGGGAA ACAGCCAGTC ATCAGAGCAC ACACAACATT1 TATCAAT~rAA GTrTATCACC TTGAGGGCAC AGGTCATGAT ACTTCAAAAC AATVACAATA ATAAAATAAA AAATCATTGA TCGCAGATCA CCATAACAGA 60 TATAATGATA ATGAAAAATT TGAAGTATTG TGAGAATI'AC CAAAACGTGA CACACAGACA CAAAGTGAGC ACATGTCATT1 GGAAAAGTGG TGCTGATAGA CTTACTTCAT GCAGGGTTGC CACAAATACT CAATCTGTAA AAAATTCAAT TATCTACATA GTACCATAAA AACAAGGTAT ACCTGTITAT ATAATCAAGA CCAACAGAAC CCTAGAGAAA ATAGCTCACT CCCTAGCTCG GAGACAT7CT AACCAACATA CACT-rACCTT TCTI1TGCT GTGTACAGAA TTCAAATCCC TGTCTCAGCA AAATTGCAAA GTATCAAATG TCATGTCCAT CTAATACTCA 65 AAACTGCAAA TGrAAGTCT TGTAAGCCCA GAGACCACTG TATATACAAG TG'rrGCTATA AGCATTAGTT CTTCTCCAAA GAAAATAGTC CACTI'GGTAG AAACAAACAA AAAGAAAAAA AAAGAAAGAA AAAACATITI WO 00/62736 PCT/USOO/08020 164 TTACAAGAAG ATTCAGTCTC TTFACCTACAT AAGCAAAAAT ATGAGATGTr CTC'rrATCAT TrTrCCATCT ATCT'rATAAT C'TGGTGCT GACTTAGACA CTCA'ITrrCC 'TrrTGTACG TGACCATGTA AAAGTrCAAG TCAAGAAAAA CTrGTITGA CAITJGTI= GCTGAGTGAT GGGTCCCTAA AAGAAATTTG GC'=GCTr TGAAAAGTTC AGCATGATAT TGTGTGAATT 'TrCATGGCT AATGATITI AGAACAGTTG TGATGTGT 5 AGGTGTITA AGAATATGAA GCATrCAGTG GTI'AAGTrG GTTGTTATAA AATGAAAGAA TATGAAGGAA AGCCTTrCTTG TC'TAGAACA CACTGATrCA CAAATAAGCA GCTTCTCTCA .AAATGTI'GTA AITACAAAAA I1?CCAAGGCA AATATAATAA ACTCCTTGTC GGTGCTATGT CTAGAAACT AACAGCCCCA AAGAAAGTCC TGACAAGGCA AAAAATATAT ATATATATAC AAATJ7GTGGA AGCAGGGTGT TGAAAGAAGA ATAAAGACTA TATAAGGACA AACTG'TTrAA AAGGGAGGGT ATCC1TGAAA GCITGACACT TGACTC1TI GACGAGGCTG 10 AGGGAAAACA CTCAGTrCA TAGATTGCTG GTACGGATGT AAAATAGTGA CATCCCTATA GAGAGGAATr TGGCAATATC TAGCAAAAGT GCTTATGCAT TTATrCM~G ACCTAGTAAT CCCGCYI'CTA GGA'TTAGTGG TGAAGATACA CCTCAACAAT AAAAATATAT ATACATTAGG FrA'TAGTTA TGGITrAATr 'TAATAGCA AAATAMTAA AACAACCTAC ATGAACAAAT AGGAGACTTA CTGAATAAAC TATGGTATAT CTGTACAATA AAGTGCAATI' CACTTFATGTT GTFAKTGT TCCAAAAATC CAGAGCCAAA GAGTA FTrGT TATGCTCTCT 15 TTAGTATAAG AAAGGGGAAA TAAGATATGT GTGCATCTGT TTATITGT GAAAATAAGT ACAGAAAGGA TAAGTAAGAA ACTAGTAAAA CTAGT7ATCT CCTAGTGTTA GTAGAAATAG AATGAAAGTG AAYJ7AGGCTT C'ITTGAGTAT ATGTTTATAT ATAGT1TGA C'TITGAATr ATGTATGT TTACATAGTC AAAAATATAA ATTAATCAAC AGAAATAACA AAAAAAGAAG AAATCACAAG CTTTAAAATT TAATACAAAC AGAAATAATr GAATCTAACA GTATATCAAA GTGATAACGT AAACTCAGAA GAAAAAAACA TAATCCAACA TACCAGTGGA 20 ACACAATATT CTAACTGTAT ACA ITCAGTG GTTATAGTCT AAGGACAAGA AAAATTGCAA AAATATCTTG AACMIAGCT TGTAGGATTT TTATTGGTAG CAATACTAAT GTACTAATrC TGAAATTAAT GTI'CGTGTAT TATAGAATrG AGTAAATGAA TAAATATGTT GATGTTATTG GGAACTAAAA YI'ATCATI'CT GGGAGTAGAG AAATATAAAT ATGGAC FrGG CAAATGAAAC AAAGACCTGC AGAGAGATAA CCATATAAAC TCATTATITT AAAAATTATA AGTGTCCTAG CTCTGPI'ACT GAAAAGGCCT AGATTCAATC FTATCTTGAT AGACAGGAGG 25 GCACCCCTTT CTCAGAACAT GGTTrCCAAA TGCCATTCTC CATrAAAAGG AACAAGGTCT TCTI7GGAGAA AAGACTGATT CTAGGTCTGG ATI'AGGTAAA GTACAACG'IT AGTCTGGAAT 'ITC1TGCTGA ATCAGAAGTA AGAAAGTGCT CAAAAACATG GGAACATGTC ACAAACACAC GTGAGGCAAC TTGAATCCTC ACTGGCCATA ITTAGGACAA TCGAGCATCA AAAAAAAAAA AAATGTTGAG AATAATGGAT TCTAACACTT AAAACAAAAA ATAATCCATA GCCCACAGAA GGGGAAGAGA GGGGGAGCTC ITATI17ACAG ATGAATATCA AATAGCAAAG 30 ACAGAAGAAA TGACAGAATT.AGAGAAACAT CATITTrGCAA AACACCACTG TAATAATCAA TFCAGGCAAG TATJ'A I1AAT GGATGTATTA CTATTGCGTA AAACCAGITG GGGAACAGGA TATTCATACA GTCTGAAGGT GTCACCCTAA ACATAACT7A TTACAAGTGG AAAATGGTGC CTTTACAATG AAGAAATCTA GCAGAAACCA TCTAATCTA GTGATCAAAC T7AGTATCAC CAATAATGGA TCATACTGAG TCATGTGTCT CCTAATATGA TGCACCAGGA AGGATGCAAC GTCATGAACG TTGTA~fCTT TTGTATTCAA CAGACCACCC AGGGTAAAGG 35 CAGC'ITTCTC AC'ITACTAAT CAGAATTGTT GGT=AA'rr CATI=GGAT 'TrTAAGAT' CTrACTTIrCT TGTCAGCTCA GAAATTTATT TAAGATGATT T1TATCTT ATTCAATACT YFAGCTTGGA GAACCATTCA GAG=~CTAA CTCATI'GTAT TGCCAAAAAT AGAAAACAGC ATGG'ITTrTT GAAAATGT CTAAC'rrrAA AGT'FACTTGT GTGTGTCACT CAGA'ITCACA TAGCT'ITT GCCTAGTAAT GTAGTATCAT GTGGCAAGGC TATAAAAATG 'FrACAATCT TTTA1TAAT ATGACTCTFG AGAGTTTAIT CTAAGGAAAT AATTGAATAG 40 TAACAAAACA CTATTAACAC AAAGCATAGC AATrGATTr GGGCAACCAA ACACTGGAAA CAACCTAAAT GTCCATTACA GGAATCATT ATGAAGCAAA CACTAAAATA T'ATTGTGA AGATTATGAG AACATAGAAG ACAGT7ATGA GAGTAAA'ITT GAAAACCTGA ACACAAAACT TACATATACT CCAATTGTAA C FTATAAAAA ATACGTGCAT ATAAGGATAA AACAGTACAA ACAAAAAAAT AG ITGCGT7A GATTGGTAGA ATTATGGCTC CITTGCTGT CTI'AATITI TCCTTTACA ITTTGATACA TL'AYIAAT TAAmA AAATTCAAAA 45 GAATTTGCCA CTCATC'TrG CCACTTCAAG GAAAAAAGAA ATGTGTTCGA TrATTCTG Fr CTTAGTATAG TITGGCAAT TTCCTCACGT GTAAAAAGAG AATACTATTA ATAA3TTCAG TATCTATAAG ACAATATAAA ATTAAAGAAT CTAGCCCAGT AACTGGTACA TGGAACGTAA TL'AATAAATC ATTATGGACT TTTTTITCTCA CACCCAAGTA GGGAGGAATC AGTGGTCCCC TAGAGGCCCA GTGTAGAGGT GUCAGGACCA ATCCCTAGGG GAGAAGATCT TGGTGATGAT AA'ITCCTGAG CAGACAGTFA GCTGAGAATT CAAGAGCAGA AAAGTAAGAA 50 AGAAACAACT TCTI'GCTAAC ACCT1TCCAC CCACGTTCC CTGTTCTGTT GTACTCTGCT TACCCT=CA TGGATGGAGG CAGAGGAAAG AGAACCAAGT T7GCTCTTAG TCATrCACTA TGTTGTTAA TCTGCCTI7CC ATCT~CT'TA TCAGTTCAAA TTAGAATGTA GACCTGAATF TAAATCCCCG TTCTGTCAGT TATAATGTGA CCCTAGACAA AACACA FrCT CTGAACCTCA GAGAACATTC TrCArT-GTA GAATGGGAAG ATTAATCTAT AT'TCCAC'rrG GATGGCAAGT CTIIATAAA C'TrATAACC TAAACATGTG TGAGTTGCTA GTATCATTAT 55 GTTGGTAAAG flATTCTGAG ATATGATAAC AGAACTG'ITT TGTCTAACTC CACTAGCATG GTFrCAGGTT AGAGAGTGTG GAATTAAAAG GCTTTATCCT CAAATATGAC 'ITAAATCCGA T11TCTCAT CCACTTFTCCT CCACAAACAA ATCCTCAGGA AATGACAAAC T'ITACATGGT TAAACATCAG 'rT=GTTTAG TC'ITTGACAT CCACATGGTI' AAATCATACA TTTGAAAACT GCTTATA TT GTGTTGTCTA TGTCTAAA3T GAAAAGAC2Fr ATTGAGGAAT AGAAGACTAC ACA'TrrrCA GCAAACACTG CACG=IIGC AGAATh~rCCC CAGGCACCAG 60 TCTCCAGGAA TPTATTGGCT ACTAACAATA CTAAGATATG GATGAATGAG GAAATCAAAA TGGAGATCTTF GCAAG'T=rG TGAGAATGGG TGAATGGTCC AAATGAAGAG ATAAGTTGTG AAATATTAGT ACAAGTAAAA ATTA TTACA ATGAAAGACA 'TITGTCAAT AGCTATGAGA A=IIACCAT TGACCCAGAA AFI'CCA'TTC TTCT'TCAGA AATACCCACG TAGGTATACA TATAAAAAGT TATTCA'ITAC AGTATCGTTT TrCATAGGAA AAAGTTAA AAATCAGAAG CTATCTAAAC TATGGTATAT CTAGGTCATA GAAATCAAAT GACTAAAAAT 65 GTTAATATAA GCATATGnTI TTAAATTAAC TGGCTGGG TCTI'CAGCAA AATTGGCTTC TI'AACATFGC ACTCCAGAGT TAGACTTACC CACTCAGTCA CTTATCATGC AGGAGCAGAC TCCTAATACC ACATATCATA WO 00/62736 PCT/US00/08020 165 GAGCAGAGTA GGACACAGGT TCTCTGCAGG CAGGCAAATC CCAAAGAGAA GGGAGGAAAG GGCTGAGACA CTGCATGGTC AATCTTCT GAACTCTGCA ATGTACGGAG GTGGACAGTG TCCACAAAGA TFTGCTCCCCT GGACCCACCA TCATAATAAC ACAACGGC'IT TG'T=G'If TTG'TITGT TIT1GACAC GGAGTTTTGC TCTTGTJGTC CAGGCTGGAG TGCAATGGTG TGATCTCGAC TCACCACAAC CTCCACT~rCC TGGGTTCAAG 5 TGATrCTCCT GCCTCAGCCT CCTGAGTGGA TGGGATTACA GGCATGCACC ACCATGCCCA GCTAATTTG TArTTrAGT AGAGACGAGG 'TTCTCCACG TTGGCCAGGC TGGTCTCAAA CTCTTAACCT CAGGTGATCC ACCCGTC'G GCCTCCCAAA GTGCTGCGAT TACAGGTGTG AGCCACCGCG CCCAGCCCAC AATGGCCTrT TG=~ACATC TCTAGTGCAG CACTCA'FrrC ATGTTCTTTC AAGAAGAATA CATATTTCAT CTI=rTIr TATACAGCAA T'rAGCACAGT GCCTGGCATA AGGAAAATGA TCATrAAAAG CTGGGTGAAA AACCTAATAA 10 AGCTACTGAG GATAGGAACT GCAGACCAGC ATGGAAAGAA AACTATGAGC CAGATATTGA CATCATCCTG AAAGGCAGAA GA'TTAGTAT AGGCAAGAAG TATGCT=TG GAATATAGAA AATCTGGATT ATGATAAGAA AAGAATCATA 'I=GTCTTAT CTTACCTACT CACTTCTCAG TCCACATGT TCTGAGGCT GTTTGTCCTT ACTTC7MT CTGTITATC CACTC'ITrCT GTTC'ITTAGA TlGGATCA1T CCTATTGAGC TGACATCAAG TTAACTGACC TTTA1TG TCCAAACTGC TGTrAAATGC ATCCAGTGAA TTMTAACTT TATATAGTAT 15 ATCTMAGT CCTAGAATITT CCACATGAGT 1TITAAG'IT TCCATTTCTC TGCTGAGATC TCCTATfTGT TCATTCATTA TGACCATA'IT TTTCTCTACA 'FrATTGAGCA TAAT7ATAAC AGCTGTTCTA AAATTCTTGT CTGCACATTC TAACACCTGA ATTATTCTGG GGTCAGTCTC TG3TACA FIG CCTTATTACA AAAACAGTAT AAGTCACATT GCC=G'TrC TTAATATGCA AAATGATT TGATTGCAGA CTAGACA'TrT TGAATTAAAC ATTATAGAGA TTCTGGATTC TCGAGAGAGT ATTGACTTGT T=rCCATC AGGCAGGTAA CTTGACTGGA 20 CTCAAACTCC AAACTCTAGG TCCTCTGTAA TGGGCAACTG CAGTAATC'I TGTFITAGTTC TFAAGACTT ATTGGCCAGG CACGGGGGCT CATGCCTGCA ATCCCAGCAC TGTGGGAGGC CAAGGTGGGA GGATCACCTG AGGTCAGGAG TTCGAGACCA GCCTGGCCCA CATGGTGAAA CCCTGCCTCT ACTAAAAATA CAAAAATTAG CCGGGTGTGG TGGTGGGCGC CTGTAGTCCC AGCTACTCAG AAGGCTAAGG CAGAAGAATC ACTTGAACCT GGAAGGCAGA GGTTGCAGTG AGCCGAGATT GTGCCACTAT ACTCCAGCCT GGGTGACAAA AGCGAGACTC 25 CCTCTCAAAA AAAAA'1AT TGGCACTGCT TGGCATCTGC TATGAATACA TGAAGTTCAT GGGTCAGCTA TAGATCTGGG CACGTTATAC ACAGAAmTG GGTCTCCCT"T TCTCTGGAT7 TCTCCT1TC TGGATITCT1' FrCTCAYTr CCAGCAGCTG TGGTTGCCCT AAACTCGGTC CTCTG'ITTCT TTACGGCAGT AAGA'ITTGGG AACTTAGG TITACCTGC CTCTCAGACA AAATAAAAAA TAA'TrTCAT CTTGATGCTA CTCC'TrTC'T CCAGATGTAG ACACCTCTCT AATrTCCAGT TGC2T=TAT TGCTCTCCAG AGTCTAAAGA TTATCATTGT 30 ThI'CTGTGGG AGAGTTGGTC TGATAAAAAC TACTCCCCCA AAACTGGAAG CTGGAAGCTT GTAATTATGA ATAGAC'ITTG AGTAGTAT1'C TTC'TTrGGAA AAGGATITA ACTACTCCCT ATGTACTTCT TTAFrrCCTG TIT=CTCAT CCGTAATCTT ITTAT=rCA TACTrCCTAA GTCAGACAAT TITCCTACTT GAAGATTCAG TGACTGCTAT CAAATGACCC CCATA FTACT AAATACAATA TCCCCAACTG CATITATAAA AAGAAAA1T17 ACTG'r=ATr AGTAAACAAT GTTGTAGAAT AGTAAAATAT TGCTGGGCTT TGGAGCCAGA TAATCAAGGT 35 TAGAATCCCA GATTCTAACT TACTAGCTGG TGTATFAGTC CTrTCTCATG CTGGTAATAA AGACATACCC CAGACTGGGA GACTGGGTAA TT7ATGAAGA AAAGAGGTT7 AATrGACTCA CAGTTCAGCA TGGCTGGGGA GGCCTTAGGA AACTTACAGT CATGGTGGCA GCAAGGAGAA GTTCCAAGCA AAGAGGGAAA AGCCCCYTAT AAAACCATCT GATCTTATGA GAACTCACTC ACTATCACGA GAACAGCATG AGGGTAACTG CCCTCACGTT TAAT-FACCTT CCACCAGTC CCCCCCATGA CACATGGGGA TTATGAAAGC TATAATFCAA GATGAGATT 40 GGGTGGAGAA ATAGCCAAAC CATATAATTC CACCCCTGGC CCCTCTCAAA TCTCATGTCC TCACATTTCA AAACTCAATC ATGCCCTCCC AACTGTCCCC CAAGGTCTrA ACTCATlCCA GCA ITAAGTC AAAAATCCAA GTTCAAAGTC TCATCTGAGA CAAGGCAAGT CCCTI'CTGCC TATGAGCCTA TAAAATCAAA AGCATGTTrAG TTACTTCCTA GATACAGTGG GGGTACAGGC G'ITGGGTAAA TACACTGATT CCAAATGGGA GAAAFI7GCCA AAACAAAAGA GTTACAGACC CCATGCAAGT CCAAAACCCA ATAGGGCAGT CATTAACAIT AAAGTTCCAA 45 AATGATCTCC TrGAC'TCA TGTCTCACAT CCAGGTCACA CTGATGCAAG AGGTGGGCTT CCAATGGCCT TGGGCAGCTC TGCCCCTGTG GCTI17GCAGG GTATAGCCTG C'ITCCTGTTT GC'ITTICAC AGGCTGACAT TGAGTGTCTG TGGCTTTCC ATGAGTATGG TGCAAGCTGT TGGTGGA'IM ACCA'I1CTGG GGTCTGGGCC AGGTGCAGTG GCTCATGCCT GTAATCCCAG CAC'TrTGGGA GGCTGAGGTG GGGGATCACA AGGTCAGGAG ATCGAGACCA TCCTGGCTAA CACGGTAAAA CCCAGTCTCT GCTTAAAAAA TACAAAAAAT TAGCCAGGCG 50 TGGTGGTGGG TGCCTGTAGT CCCAGATACT TGGGAGGCTG AGGCAGGAGA ATGGCGTGAA CCCAGGAGGT GGAGCTTGCA GCGAGCTGAG ATrGTGCCAC TGCACTCCAG CCTGGGCGAC AGAGCAAGAC TCCATCAAAA AAAAAAACAA AAAAACCA'I17 CTGGGGTCTG GAGAATGGTA GCCC'ITACAG CACCACCAGG CAGTGCCCCA GTGGGGACTC TGTGTGGGGG CTCTGACCCC ACATTTCCCT TCTGCACGGC CCTAGTAGAG GTTCTCCATG AGGGTTCTAC CCCTGCAGCA AACTTCTGCC TGGACATCCA GGCATCCA TACATCCTCG GAAATCTAAG 55 CCGCGGAGGT TCCCAAACTT CAATrCTTGA CTCCTGTGCA CCCACAGGCT CAATACCACA TGTAAGCCAC CAATGCTTGG TCAGGGCTTG AACCCTCTGA AGCAATGGCC TGAGCTGTAC GYI7GACACCT T'I1AGCCTAG ACATCTAGGA CACAGGGCAC CATGACCCGA AGCT-rCATAA AGTGGGAGGG CCTL1GGGACT AGCTGAGGAA ACCATrI=C CATCCTAGGC CTCCAGGCCT GTGATGGGAA GGGCAGCCAT GAAGGTGCCT GACATGCCCT GGAGACG'LTT TCCCCATTGT CTI'GGTAACT AACATTCAGC TCCGTGTGCA GCACCAAC117 ACTTATGCAA 60 ATTCTGTCA CTGG'IMGAA nITCTCCCCA GAAAACAGGA rrrrrrnTr CTA'GCATC ATCATGCTGC AAAFTTTCAA ACTTTTATGC TATGCTTCCT GTTGAAGACT TrGCGGC'rrA GAAATTrrCr CCCCCAGATA CCCAAAATTA TCTCTCTCAA GTTCAAAGTT CCACAGATAT CTAGGGGACA AAATGTTGCC AGTCTCThTG CATAGCAAGA GTGACCYITA CTCCAGTTCC CAACAAG'Tr CTCATCTCCA TATGAGACCA TCTCAGCT~rG GACTTAGTTG TCCATGTTAC TATCAACATT TTGGTCAAAG CCATTCAACA AGTCTCTATG AAGTh17CAAA 65 CTI'CCCCATG TITCCTGTC TTCTAATAGC CCTCCAAATF =~CCAACCT CTGTCTGTTA CCCAGTTCTA AAGTCACTTC TACATTG GGTATCTA CAGCAGTGGC ACTCCCCATG GTACTAAnI7 ACTGTA'ITAG WO 00/62736 PCT/USOO/08020 166 TCTG'FrCTCA TGCTGCTAAT AAAGACTTAC TCGAGACTGG GTAATrTATA AAGAACAGAG GT7CAACTGG CTCACAGTTC AGCATGGCTG GGAGGCCTCA GGAAACTTAC AAACATGGTG GCAGCAAAGA GAAGTTCCAA GCAAAGAGGG AAAAGCCCCT TATAAAACCA TCAGATCTTG TGAGAATTCA CTATCATGAA AATAGCATGA GGGTAACTGC CCCCATGATT AATTTACCTC CCACAGGGTC CCTCCCATGA CAGGTGGGGA TITATGGGAAC 5 TACAATTCAA GATGAGATF GGGTGGGGAC ACAGCCATAC CATGCCAGCT AGAGAGCCTr AAGAAAGTCA CCTAATCTCC ACAAATAAAA GGTITCCTAT TTGTTCAACA AAAATAATGA CACCCG'=r ATGGGA'rfrC TGTGAGGACA AATGATAACT AACATAGCCT TGCATAGTGT CTGGCACAAA ATAGCTACTC AAAAAATAAT AGAAACAACA TTTAAAAAAT GTAGAC1IA TTITAGAG TITATGTAC AAAGCAAAAT TGAGCAGAAT GTACAGAGAG TITCCGTATA GCACTCCCTA CCCCCAAGCA CAGATAGCCT CCCCCAGTAT CAGCATCCCG 10 CACCAGAGTG GTACA'TTTAT TATAACTGAT GAATCTATAT TGACGTGTCA 'm1CATCCA AAATCCATAG 'IMATATTAG GGATGCCTCT TGGTG'ITGTA CCTTCTATGG GT'IMGACAA ATGTATAATG ACATGTATTC ACCATTACAG TATCATAAAG AATAG ITTCA CTGTCCTAAA AATCTITGAT C'rrCVCCTA 'ITCATCACTC CCTCCCCATT AATCCCTGAC AACTACTGCT AAY1TCCTG TCTCCA'JTGT TTTGTC'TM~ CCTGAATGTC ATATAGTA AATATACAGT ATGTAGGAT]? 'TCAAACTGG TTTATICAC TTAGTAATAT GCA TTGATG 15 TTC'rrCCATA TC'TrrCAAA GCTTCATAGT TCAATAMTA TAGAATrGAA TAATA I1'CCA T~rGTCTGGAT GTACTACAGT TTATGTATTC ATI7CACCTAT CAAAGAACAC CYrGGTTGCT TCCAAGTJTC AACAATCATG AGTAAAGCTG CTATAAACAT CTATGTACAT G TT1TGT GAATTGAACA TIMCAGCTT T=AGCTCC ATTCCTAGGA GTGCAATTGC TGGATT1GTAT GATAAGGGTA TGTrAGTGT TGTAAGAAAC TGCCACGCTC FrCCTAACTG GATGTACTGT TTrGCA'FrCT CACCAGCAAT GAAAGAG'rrC CTGTTG~TCC ACATACTCAC 20 CAGCATTGG TGTCGTCAAT G'IFIGAGCA ATAGCNTF GATCTAACTT TTCCTAGGTA TTCTITGA AGGAAATAAT ATGACAGATA ATAGAGAAAG GATATACGAG GACAGYrCTG TCC'TrTATTT ATAGTCCATC ATrAATGAA GGACTCTGTC CACACTTGGT A'TTIAACT CTGATCCTCC TCTCCCATGA ACTCTGACAA TCTCCTAAAT CCCTG'TrGCT GGCACACATG GT]7GTGTATC AGGCCCCCTG TGGTCTGTCT GAAGCATGGC TTM7TTr rIT~rTT= TT'TITGAG ACGGAGTCTC GCTCTGTCGC CCAGGCTGGA GTGCAGTGGC 25 GCGATCTCGG CTCACTGCAA GCTCCGCCTC CCGGGTT1CAC GCCA'ITCTCC TGCCTCAGCC TCCCGAGTAG CTGGGACTAC AGGCGCCCGC CACCACGCCT GGCTAATT TTGTA'TI= AGTAGAGGCG GGG'TTCACT GTGT'FAGCCA GGATGGTCTC GATCTCCTGA CC'flGTGATC CGCCCGCCTC TGCCTCCCAA AGTGCTGGGA TTACAGGCGT GAGCCACCGC GCCCGGCCYJ7 'fTI11TTTT 'Tr~TT rrr1 ITrGAGATGG AGTCTGTCAC TCTGTCACCC AGGCTGGTGC AGTGATGCAA TCflGGCTCA CTACAACCTC CATCI=CAG GTTCAAGTGA 30 TTCTGCCACC TCAGCCTCCC AAGTACCTGG GA I7ACAGGT GCCCGCCACC ACACCCAGCT ATTIT=GT A'T=AGTA GAGACGTAGT TTCACCATGT TGGCCAGGCT GGTCTCATrC CTGACCTTrGA GTGATCCACC TGCCTTGGCC TCCCAAAGTG CTGGGATTAC AGGCATGGGT CATCACATGT GGCCTGAAGC ATGACTGTTG C'ITTAATCAT ATGAAATACT GCTCTGTATT GTTATCTATT TGAAATGCCA CACCTCCTGA GCTAAATTGC AAGC'IIAT GGAGCACAAA CCATA'ITTAT ATATA'FrAGC ATGATACCAT GACACATATC AAAAGCTGTT 35 ATATATTGTT ACGTGAA'TrG ATITrCTC AGTTAAGAGG ACCTCTGTAG TAGCACIT'C ATACCGP-rAA 'TTCATTT TGTGCCCAGC CCCTACTCTG TGAAAAATGA AATGAATCCT G'I1ATCA ITT CCCTCCCAGG CCTTCTCC TTGTGGACAA TGTGTGGCTC AAGAGAAAAT TCAGTCAGTA AAMTTGT17CA GTGCACAAAC TC'ITTATCAC CTCTCACTGT TCTCAAGTGA GATAGAACAG AACATCCATC CAGTGTCLTA CAAA'ITGTCT GGTATATAGT AGGCACTCAA TAAATGT1T TrGAATAAAT GCATACATGA ATCCTATTCC TATATATAGT 40 ATGGTAGACA GATCATTGAT ACCCAAAGAT GCCCAAATGC TGATCCCCAG AACTTGTGAA TATG ITACAT YrTCATGTCAA AAGGGACTTT GCTAATGTGA TT1AAGGATTC AGACCCTI7GG A'I1GTAAGAT TATCCCGGAT TAACCAGGGC CAATCTAATC ACATGAGACC TTAAAAAAGC AGAAAACATT TCCCAGCTGG GTTAGAGAGA GATGAGACAG AGTAAAAAGG AAAGAGATTC AGGGCATGAA AATGACTCTA CCCACTGTTG CTGGCTTTGA AGATAGAGGA ACTAGGCCAC AAAACAAGGA GTATGAGTGG CC'ITAAGAAA TAGGAAAAAG CCCTCATCTG 45 ACAGCCAGCT AGAAAGCAGT CCTCTGACCA CAAGAAATI'G GATVCTGCCA ACCACTCAAA TGAGCAAGGA AATGGATTCT CCCCTAGAAC CTCCAGAAAG GAACACAGCT CTGTAATGCC TI-GATI=AG CCAGGTGAGA CCTG'ITTCAG AC'I=rGACC TATGGAAATA TAAGATAATA AAG'TrTATI7 GTATGCTGCT AAAThTGCGG TAGTI1'ATTA CTGAAGCAAT GGAAAGCCAA TACAGACAGA ATATACAGAG AGAAAGAGAA TGAGTTCTTT CCTGATAATT TGTAAATATT TGGGTCTTCA CTGGACAAGC 'ITCACAGAGG ATTCACTGGT TCCCTAGCAA 50 ACCAGCATGT CCAGTCCTGC AGCCTCCMr TCTTAGGCCC AGCATATGTC AGCTGTGTGC ATAGAAAAAT CAAAGCAGGA CCCTGAGTAG TTGGAAAGAA AAGATGGTTG GAAATGGGTT GCACTTCAAG TGAGGAAACA AGAGGTAGGA GACCGGCATC TCTI1CTCAT ATGTCCCAGG CTGACTCTTG TGAGTI'G'I TCCCTTGGAG GCTATCGATG ACAGTCACAG TAACCTGATG GAACCTGGAT CATGATGAAA GAAGTAAGTG TCAATGGCTC CGACTTCCAA GGACTCTGAT GTCCCACAGC ACTAGCTAAA CAAAGCCAGT TGGAAATGAG CTTAAATGGG 55 GAATTTCCTG AATATATTCC CTA'rrGTTAG GAAGCCAGGT TGGCTTCCTT GCCTACAATr ATGCCAAGCA GTCACACTAT AGAGTCCCTA GGGACATGAT ATTAAGTGAT TCTI=TAACA CAAACAACTT AATAATCATTF TATACTAATA GCAAAACGGC CAACGGCTGA TATTCCACT GAAGTAGAAT TGGCTATCCA ACTGGAAGAG AAGACAGGAA GACGTGATCT CCAGGGAGCC ACTAAAAGGA TTGGCACCTG CCTCTGGATT CCCC'TTrCC TI7ATA'ITACC TCTCAGCACT GGCAGGCCTT TATCAGGA TACAG'TrCA CAAGTATrAT GTCACGTCTC 60 TGAGAATTAT GTTGGTAGAT A'ITTGCTCCT CTGGCCAGAA AGACCTAGTT TGGAGTCTGG AGTCATGAAG GTGACATACA TGTAGCTAGT GACATAAGTG TAGCTAGTAA AAATAGTGAG TAATGGCCCT GAAAT'TCTAT TGAATGCCCA AAGTGCTGAC CAGGAACAAG CATGCTCTAG CTTATCTCAC AAGGAACTI'G ACAAT ITTCT TCAAAAATCC TAGTAGCTAA GATCTTAG TAACAAAGCC ACTAAGGCAC AATTATGA11 AAC'PTGACCC TTAGGTGACT TTTAAGGACT ATTCTATAAA ATA'rrACAAC TAATAGTGGA TCCAAGCCAG CACACTCTGC 65 TATATAAGAT TAATTGACAG TGTCCACACT GGTAAAATAA GTTG'TrCAT AAATACA11A GAA'FrCATr GCAC'I=CTA CACAGCCCCA AGTCCAGAAC TrCCCCAGA ATAGGTCTAT G1TIGCAAT CTGCTACTCC WO 00/62736 PCT/USOO/08020 167 ATACAGAGAT TTGAGTTCAC TTGGCAA'ITr AGTGCTGCTT ATATGTGACC AGTTAGTCTG T'FTrACTrAT CTATGCCTTFA AACATTACTA TACTTACTAA CTCCAAGATG CCTGGTCTCA ACTTGACAAA AATACCCCAA GTrTGGGAAAT CCTTATGTGA ATATGTAGAT AGTCACAATr GCTGGTTGAT GATGATCTGT CT=TCCTGT AMVGAGAAA ATGGAGATAA AATGGACCAA TCCAAATAAT GGATTAAACA TGGGAATAGG TGAGAGAGAG 5 AGAGGAATAC ATGGTGGCTC TCAGTGTCTG GC'ITAGGCAG TAAACACTrT CGTTAATAAA GACGGAAAAT AAAAAAGGAA TAATTGGTGT CTAGGGGAAA ATAATGAGCT CAAGTITAA CACTCTGAGT TCCCGGATGT GAGACATCCA GGCGCA'TrA TCCAAGAGGC AGTI7GGAAGC AACGTTCCGG AGCTrAGGAG AGAGGCATGA CCAAAAGCTG GTGGGACTGT GAAAAGGTAT GGCCATTCTG GAAAACTG'IT TGGCAGTC TTAGAAAATIT AAACATGTAC TAACAACCCA GCAATI'GTAC TCTTGAGCAT TTGTCCCAGA TAAATGAAAA AAAAAAAAAG 10 CATTTT ACACAAAAAC ATATACATGA AAG'ITCATAG AAGTGTT1ATT CATAAAAAAC TGGAAAAAAC TGAGATGTCT TT1A'L17GAGTG AATGCTTAGG CAAACGGTGG TCTATCCATA CAATGGAATr ATGCTTAGCA ATAAAGAGAA AAGAACTAT[ GATACATGCA ATAACACAGA TGAATCTCAA AGGAATTAAT GCTGAGTGGG AAAAAAAGCA CATCTCAAAA TGGTATATAC TGTACTATTT TA1TTACTTA ACAT1TT7AAA AATAGCAAAA TCATAGAGAT GGAGAACAGA TTAATGGGTA CTGTGTrffG GGATGGGGAG TGAGAAAAGG GTAAGGTGTA 15 AATATAAAGG GGTAGCACAA AAGAGCCTTG TGGTTGAAGG ATTCTATGTC TTGGYrGTAG TCGTGATTGC AGGAATCTAC ATGTGATAAA ATT1GTATGGG TCTACATACG CATACACACA AGAGCATATA AAACTGGTGA CATGTGAAGA AGCTCCGCAC A'ITGTGCCAA CATCAGTATC CTAG'TrCAA TATCAGACTA CAGTTATACA AAACATTGTC A'PrGAGGGAA ACTGGGTAAA GGGAACACAG GACA ITTGGC ATATA'TI= GCAATTTCCT GTGAATCCGT AATTA'ITTAA AAATAACAGA TATACTACAT ATCAAAAAT TAATGTCATA AAGTTGATGA 20 G ITTACCTAG TGGATAGCTT TGT7AATATC TGCTATAAGA CTACTGAAAA TGACAGTTAT GCAAGTATAA GCTCAGAGAA C'ITTCCTCCC CCTTCGTAAA TGAAATGAGC AAAAGAAATG AAACAGGAAA GGCAAGCAGT ACTGAAAACA GGGAAGGGCT CTTCCCCATA TAACTATATC TGCGACTTCA ACAGCTATTC ATCCAGAAAC ACAGCCTC'IT GCGCTAAGAG GAAACTT1TGG ATAACAATAT GYITCACTC TCCAAGAGAG AAAATGGATA GATTAArrr TAAGAAAAAA AAAAAAACCT CACCAATTTC ATGCTGTGGC TTGCACCT AATCCCAGCT 25 ACCTACAAGG CTGAGGTGAG AGGCUTACT-T GAGCCCAGGA GTrCAAGGCT GCAATGAGCT ATGATTGATT GTGCTATCGC ACTCCAACCT GGAGTACTAA GCTAAGAGCT AAGAACACAG CTGAGAGCGG AGAAGAAACA AACAAATCTG ACCAATAACC CCCACTCCCC TCA'TMIACT GGAGTGAGCT GAGACTGCTG GCAAACATGG CCTJTGACCT AGCCTGAACT GTAGCAAAAG TCATCAGATA ITTrCCACC AATCAACAGA CAGAAGTGGG GAGAAAACAA TCGTAGTL'CA TAACTACAAC AAGCAGATAA ACGAAGGCCA TGGTGAGGGA TGGAAGACAT 30 TGTGATATAT CAAAGGCAGG CTCA'TrTAAA ACTCAACCCA AA'I1CCAAAC AAAATATATA ArrFGAATATG TATTAATGCC AAAGGAGCTT GAGTGAGCTI7 TAGCACAAAC CCCGCCCTCC AGCCCCCACC CAAAAAAATC ACTCTGTTCT CTCCCCATT1C ITTrGATAGGC ATACTI'GCTG T=1CTCACA GCCAAGGTAC AGAGGGGACT TAGAGGAACT AGAACTCTAA TACACTGCTA GCAGGAATGT AAAATGAAGC ATCTACTTCA GAAAACCATT TTATCAGTTT CTAGAAAG'fr AAACATAGAC CCACCATGCA GCCCAGCCAC TCTACTCCTA AGTATrTACA 35 CAAGAGAAAT GAAAACGTGT CCCCACACAG TTGTArrAA AGGTGATGGT TAGCCT-TGTG TGTCAACTTG GCTAGGCTAT AATACCCAGT TACTGAATCA AATAGTAATC TAGGTGCATC TGTGAAGGTA Tr'JTGTAGAT GTGGTTAACA GCTACAATCT GTTGAC2FTCA AGTAAAGGAG ATTGCTCTIG ATAGTATGGG TGGGCTTCAT CCAATCAATTr GAAGGCCTTA AGAGCAAAAA GTAAGGTITC CCGGAGAGAA AGAAATTCTG CCTCAAGACT GCAGCCTCAA CTCCTGCCTG AG'ITrCCAGT CAGCCAGCCA GCCTAAAGAT TTGCTAGGCA TTrATAATCAC 40 ATCAGCTAAT 'rrCTrAAAAT AAACCTC=I ATATATATT1G ATACAATGAA TGGTrFATAGC AGCC'rrA'I GTAATAGCCA CAAACTGGAA ACAACCTAAA TGTCCTTCAA TAAGTGAATA CATAAACAAA FrGTGGTATA TCCACAATTT I17ACGCAGCA GTAAAAAGGA ATAAATGGTr GAATAAGGAA TAAACACATA ACAAGGATGA ACCTTAAAAC CGTAAGGCTG AATGGAAAAA GTCAGACAAA ACTAATACAT ACTGAATAAT TCCATTTATA TrGAAGTTCT AGAAAATGAG GACTAACCTA TAGTAACAAA AAGCAGAAAA KI=fGCCCA CTGGTGATGG 45 AGGGGGCGCA GGTATT1GTAG AGTATCTGAG AAAGGACAAC TGGATAAAAG GGGGCACAAG AAAACTTTG AGGGTGA'ITG ATATGTT1CAT TATCTGTGG CATGGTITCA TAGGTGCATA CATATGTCAA AACATCAAGT TATACACTTl' TAAAATGTTC AG'1ACTGT ATATCTATTA TAC'ITCAGTA GAGAGGAAGG AAGAAAGTGG GCAGGGTGGG GGAGAGGAAA GGAAACGAGG GAGGAAAGGC CCTAATAGGA AGGA=FTGG AGTTAGATT TTAAAATGAT AAAGGATGTT TGACACTCTA GGCATATGAC GAATATAGGA TTATGAGTCC ACAAAAACCA 50 CCAGGAAGTC ATGTATGTTT ATACTITTAA GTGAAGGATC AGTGGA'ITAT CAACTCCCTA ATGCT'rrGCC TCTCTATGAC TGGCTGCTGT CCTTCTCATC CCAATACTCC TTCCAAAGCC CCYI7GCTTAA ATGTAAGCCT TCTr-CCTCC TT'CAACACA TCCTGCAlC CGTGACAAAA TAAGTITCC TTAAACAGAA TGTACAGCAT ATTATTTGTA CAATTAAAAA TTGGCCA GGTGTGATGA CTCATGCCTG TAATCCCAGC AATTTGGGAG GCCGAGATGT GTGGATTACC TGAGGTCAGG AGTTCGAGAC CAGCCTGGCC AACATGGTGA AACCCTGTCT 55 CTACTAAAAA TACAAAAATT AGCTGAGTGT AGTGTGGCAG GTACCTGTAA TCCCAGCTAC TCAGGAAGCT GAGGCAGGAG AATCGCTTGA ACCTGGGAGG TGGAGGTTGC TGTGAGCAGA GATCAGACTA T7GCA FTCTA GGCTAGGAGA CAGAGTGAGA CTCGGTCCCC AAAAAAAAAC ACATTTI T AATGTrC CTCCTITGCCT GTAGGAAAAA GGCTCTGACT CC'I1AGCCTG GGCATCAGAG CTCTATCTAA ATGGACTrTA ACCTGATTT GTGGCACTAA TrCCATTGCA GTACTTGTCC GCTCACTGGC CTGTGCCTCT CTGCCACTAT YTTGGAATA 60 ATGTCCTCTC TCCATCITGT TTACTCAACT ATATCCAACC TCTAAGGCTG TGCTCCTACA AAGCCTCCCC TGGCTACTTC AGCCCACAGA GATA'IMAAC TGCTCTGCAG TTCAGGACAT TCTTCTGACT CTTTAAATCA CATTTACTTA TATATGATCT TGTGATA ITT TTTGFJGACG TGTACTTT AATfTTIC CATAACCTAT TCATTCAACA AACTCAACAA 'ITA'TTTATFIA AATGCCAAGT TAGAAAAATA TrATTGA'TrF TATATAGAtf ATAGATATGT TTGAAAT1T A'I=GGCAAT CTGCAAGTAG AAAAATAATI' ATAATGTGGT ATATCTGTGA 65 TAGAAGTATT AGTGCAGAGA CCATGGGGAA CATAATCCAG CCTGGAAGTr CAGGAGAGAT ACGTGGAAGA AAGGACGTCA GAGCCTITI CCTACAGGCA TGGAAGAAAC A'rTAAAAAAA AThTTfl' TTGAGATGGA WO 00/62736 PCT/US00/08020 168 GTCTCACTCT GTCTCCCAGC CTAGACTGTG GTGGTGCGAT CTCTGCTCAC TGCAACCTCT GTCTCCCGGG TrCAAGTGAT TCTCCTGCCT CAGCTTCCCA AGTAGCTGGG ATTACAGGTA CCTGCCACAC ATGGATGATA AATATGATCA TATTTTCTTG TTCTTTTCCT CCTCAGTrGT CTTCCCTGAA GAAAGGAATG CCTTTTATAG ATGACAAACT CCCATTCTCA AGAACAAGGA TTGACCA ATTTAATTTA ATCAGATGTC TGGCTTTGAC 5 CTAGAAACAC AGTCACGAAA CTTGGTGATT AGAGACCAAT TCCCAAACAT GAGCATTTCT TAGGAAACAC AGTAAAGATC TGAGAGACCC AAGAGCAGAA GGGCGAGAAA CCAAAAGCCA TCAGTTTGCA TAGGAAACAC CTTGTTTAGC CTAATCTT TATTATT ACTCTATTAG TCACTACAAC TATTTTCTGA TFGCTATGGT GATAGATGGT TTAAAACAAG CCTTCATTAA GAATTGTCAC ACCATGGTCT CAGTCAAAAA CACCAACATT TTTATTGGTA TTGACAATTA TGGGAATATC CAATTCCAAG AAGACAAGGA GACCTCTGAA CTTrCTAAAT 10 GAAGACTCCA ATCTTCCTGA TCTGATGGGA AGCAGCTTGG CAAGATTACC AACCACCACC ACAGAGAGTG GACTCTAAGC TAAGACTTAA AAGATAAGTA GAAATTATCC AGGTAAAGAT GTGTACAGAG AAGGAAGTAC ATCCAGGGGA AAAGAACAAT ACGTGCAAAA GTACGGAAAT GGTAAAAAGT AATACTACAT AGTCAAAGCC AAGCAGAGTT CAGAAGGGAT CTGGTGGTGA AAAATACGGC TAGAGAAAGC AGCAAGGATT GGCTTCTAAA ACCTATGTAG TATCTTGGAC CTTACCCTAA ATGTAATGAG AAGCTTCTAA AGAATCTTTC ATTTATTCAT 15 TCATTGAACA AATATTTGA GGCTTTCTGT GAAGAACATC ATTCTAAGTA GTAAAGATAC AGCAGTGAAT AGGACACATA AAATCCTAGA TCTCACAGAA TTGACATTCC AGAGAGGGAA AGGTAGACAA TAAATACATA AACAAATCAT TTAACAAGAT GATTTCAGAC AATGGTACGT ACTGTGAAAA AAATGAAACA AGGTAATGGA CAGCGAAAAG GCACTGGAAG GAAGCCTGCT TACCTGCA TGGTTAGAAA AGATCTCTCT AAGAAAGAGA CCACATGTGA GCTGCGACCT GAAGGATACC GAGAAGCTAG GTGTGCAAAG ATGTGGGGAC AGAACTTTTG 20 GACTGAATAG CAAATACAAA TGCCCTTGGG TGCAAGCTTT GCCTGTTCAA GGACCAAAAA GAAGGCCAGT GTGCCTGCAG CATACTAAGC ACAGAGGAAA ACACTGTTAT ATGCTGAGAT TGGAATTATA AGTAGAGCCA GATAATATAG TCTCTTATAG GTCATAATAA GGCAACCAGA TITTATTCCA AGAGGATTTA AAAATCACTG GAGGTTTTGC ACTAGGGTGA GAGGTGTGAT TTGTATTT AAAAGATAAT TCTGGAGAAT TAACTATAAT GAGGTAGGAG TAAACTAAGT TAGGGGCTAT TTCAGTGGCT CAGACAAGAG ATAATGGTAG CTTAGACTAG 25 GATAGTAGTC GTAGAAATAA ATAAAAGTGG CACTCTACTT TGGGGGTAGA GTCTATAATA GGTGGTTT ATGGATCATA TATGAGAGTA AAAAAAAGAA AATAAATTAA TAATGGTTCC TAGGTTTGTA CCTGAGCAAC TGAATAAATG GGTGCTGTGA ATTGAGATAA AGGAGATTGA GAATCACAGG CTTTGTTTTG CAAATTAATT TTGAGAGGCT TATTAGACAT CCCAGTGGAG ATTTCAGGTG AGTGGAGCCC ATTGAAAGGT AAGGGACAGG GTCAGGTGTG GTAGGTCAGG CCTGTGATCC CAGGACTTTG GAAGGCCAAG GCAGACAGAT CAGTTGAGCT 30 CAGGAGTTTG AGACCAGCCT GGGCAACATG GGAAAACCCT GTCTCTACAA AATATGCAAA ATATTACCTG GGCATGGTGG CATATGACTG TGGTCCAAGC CACTTGGGGG GCTGAGATGG GAGGATCACT TGAGTACAGG AGGCGGAGGT TGCAGTGAGC CAAGATCTCG CCACTGCAAA CCAGCTTAGG TGACAGAGTG AGAACCTGTC TCAATAAATA AATAAGAAAC GTAAGGGAAA AGGAAATTAA TCTGATCATT GGCAAATGCA TAGTATTTAA AGCCAGGGGA GTAGATGAGA TACTCAAAGT AGGTGAAGAT AAGGAGGCAA TGAAGGCCTA GGACTCTGGT 35 GTACATTTAG ATGGTTATAA GAGGAATAGA AACTGGCAAA ATAAGTAACA CTGAGCACCC AATGAGGTGG AGAGGAAAGC CAGGAGATGA AGCATCATAG AAGGCAAGAG AAGAAGGGTG TCAAAGAGGC GAGGCAGTCA TCAACTTCTG GGCAGTCAAA TAATATAAGG ACAGAAAAGT GACCATTGGA TGGAAATA TGATGAGCAC TTTGAGTGGA GTGTTGAGAC AGAAGACCAA TTAGAGTAGA TTGAGGAGAT AACGAGAAAT GAGAAAATGT AACCTGCAAG CACAGACAAT TCTTGAGAGA CTITTCTGTG AAAGGAAACA GACACAGAGT CTTAGCATGT 40 CTTGTCTTTC TATGGGAAAT GTAAATAGTT TGAGATCAGG GATAGTATTT TATTCTGCTT TTGTACCTC TACATTACCT AGCATAGAGC TAGCTAATGT GCACTTAAGT ATGTrCTCAA TTCTTATCGC CTGAATGACT GGATGGGTGA AAGAATGGAT GGATGGATGG ATGGATGGAT GGAAGGATGG ATGGATGGAT GGAAGACTTC TGA'TTGCCA AGAAGAGGAT ACTGGTAGCA GAAATAAAAA CAGCACTGGA GAAAGAAGAG TTTAGATTTT TATTCTTTGG TGTCAGTTAG ACAGGAAAGT AAGACATTAG AAGAGTCCTT AGATAATTTA TGTAATTGTT 45 CACTTAGGAT TITTAAATGT GATCACTGAT ATTGGACATG TTCCTAGTGA AGCATTTG GTGTTTCACT GGTTGAAGTT AATAACTGTA AAATTATTTC CCGTTCAGGA CAGAAAAACA GAAAACTT7GA AGCTCCTATT AGAAAGTTCA AGATTCTCTG GGGTTCTTAG GATTTACTGT TCCCAAAACT CTGTCAAGAA CAAGAAAATG ACCTGTATAC TTAACTGGTC TAGGCAACAG TGGAAAGACA ATTCTCAGAG AAGATTTGTT TTAAGAAGAC ACTCCATA GGAATCAAAC AATAGCTTTC AGTGACTAAC ATGGTAAGAC ACAGGGTGTT AGCTCTTTCC 50 TTCCAACCTC ATGGCTGTTG TACCTTACCT TTCGACCCCG TGTTCCTGAA ATTGTTAAAT TCATAAACTT ACCAAGGACT AACCAGCCTC TGGGGAATTG CTGTATACTT AGCAAACTTA CAATGGACAT ATTTATAAGC CATAATGATA ACTGACTAAT AGGAAATACC CTCAACTGAA AATGAGAGAT CATCATTGC AAATGAGITTC CCTTGCCCAG GCAACTACTG GGGAAAATGT CATGCAAGCA AAATTAATCT TTGAAATCCT CCTTTTCCAT TTTTGTGTC TTCCTTTTCC ATAGGCACCA GAAATATCAT GGTGCCTGGA TCTCATCTCT ACAGAAAAAA 55 AAAGTGATTT GATAAACTGA TTTATATTGT GTCCAAATGT GATTGTATTT TCAAAGATAA CCTAAGGGGA GAATGCTGTC TGGCCCAACA GCAGGCTCTC GACTTCATTT CAGACACTGT GGCCAATGGC TGGGAAACAG GTATGAACAG TAGGTTTCTG AGTCCCCTGG AATTATTCCA TTTATGTAGC CACCTCCATG ACAGGAAGCC TCCCTACTCT TACTTCCCAG TTTGTTCATT CATGGCACCA GGTTGCAGAT TAAAATTTGC TCAGTGACCT TTTATCTAAT AATGTGTTAC CTTCTrCTCT TAAAAAGTAC AAGGGACAAA TGCTCATGGT ATACTTTTAG 60 GAGATTGTGG CTCTCTATTA ACAGTATTA TTCAACAAAC ATTTATTGAG CATTTATATG TGCATCATGC TAGGGACTGG AACCTAGTAA GTGTAGCACA TATTATTTCA TTTAATCCTC ACAACAAACC CATGAGGTTG GTTTTATGAT CCCAATTT CAGAAGAAGA AACTGATATT CAGAACCAGT TAACTAACTG GTTCAAGGTC ATGCAATTTC TAAGATACAG AACCAAGAGT CAAAGACATG ATTTTAAACC AAAGCTTT CTGCTACTCC ACATTGCTTC CCTAGGTGAG ATCTGAGGCA TTCCGCGAAA AGAGAAGGGT CATAAAGCCA AGGGAAGACA 65 AGCTTAGGAA AAAAAAGGGA AATGTCCTAA ATAAACAGCT TTCCTATTTA CCAGAAACCA CTAGTTTAAA AATATAATGG GAAAAATCCT ATTCACTTTA ACAATGTTAA AAAAAAAAAA GATAGAAGAA ACATAGGGAT WO 00/62736 PCT/USOO/08020 169 AAACTTAACA CATTTGTAGG ATATGTAAAG AAACTAAAAG ATGTTAATAA TGGCCTAAAG AAAAAAAAAC TTACATGTAT GGGGAGATAG ACCATCTTAC TGGATTCTAA TATTTAATAG TCTAGGTGTT CCATTTCTCA CCAAATTAAT GTATACATTT AATACAATGT CAAACGAAAT ATCTTAGGAA TTGCTTACAA ATTGTCAGAT AATTACAAAG TTTACCTGGG AAATATAAGC ATATATGAAG AGTGAATGGG ACCCCACCAC TCCCCCCAAA 5 ACAAAAAAGG TCTGAAAAGG ACAGAAATCA AGGAGAGTCT TGCCTGCCAG ATACAAAATT CTATTATAAA GGTGTATTGA TGAAAACAAT TTAATACTAG TGTAGCAATA GGCAGCAAAG CAATGAAACA GCATAAAAAG ACCAGAACTA TACCTAATTA TGATGAAGAT TTAAGGTATG ATAAACATGA CATAATTCAA ATCAGCAGAA ATTGGCATAG ATAGGGTTAA GACAAATAGC TAATCATTAG AGGGGAGGAA GGAAAGGAGG GAGGATAAAA TTAGGTTCCT GCCTTCATCT TACATTAAAA TAAATTCCAG ATGTATTACA TTTAAATT TTTAAAAAAA 10 GAAACCACAA AATACTTGAA GAAAATATAA GTTGTTATAT AGTCTTTTGA TGGGAATTTT TTTrrTTTC AGAGACAGGG TCTFGCTCTG TCACCTAGCC TAGAGTGCAA TGGCATGATC ATGGCTCACT GCAGCCTTGA ACTCCTGGGC TCAAGTGATC CTCCCAGCTC AGCCCCCCAG GTAGCAGGAA CTACAGGCAT GCGACACCCC ATCCAACTTA TTTTATTT TTTGTAGAGA CAGGGGTCTT GCTTTGTTTC CCAGGCTTAT CTCGAACTTC TGCCTTCAAG CACCTCAGCC TCCCAAAGAG CTGGGCTGAT GGGACATTTT TTAACATAGT GCCACATTAC 15 CATAAATGAA AAGCTTGTAA AATACTAATT' TTTAAAACTA ATATATATCA GAAATTA TAAACAAAGT TAAAAAGCAA ACACAAAAAA TTTGTAGCAC TTATGACAAA TATATGTATA TATATGAATA CAAAAAGAGC CTTTACAAAA CAGTAAGAAA ACAATGAATA CTCCCAATGG AGTATTCAAA ACTAAACTGC TAAAAGCAAT TCAAAACAAA AAACATAAAC TATGCATATA TGTATGTGAA AAAGTAAC CTTATCAAAG AAGTAAACTC TCAAAGAAAT AAACATCAAA TAAGGAAATA GCCTTCCC ACAAATAACC AAAATCTGTA AGAATACTGA 20 GCTGCGAATG TTTCAGAAAA AAAAAAAAAT CATACACCTA GTTCGGCATG TAATTAATAT AGATCAGAAC ACTAAAAA TAYTATAGG CCAGGCACGG TGGCTCATGC CTATAATCCC AGCACTTTGG GAGGCCAAGG CGGGTGGATC ACCTGAAGTC AGGAGTGA GACCATCCTG ACCAACATGG TGAAACCCTG TCTCTACTAA AAATACAAAA ACTAGCCAGG CATGTTGGCG TATGCTGGTA ATCCTGGCTA CTCGGGAGGC TGAGGCAGGA GAATTGCTTG AACCCAGGAG GTGGAGGTTG CAGTGAGCTG ACATTGTGCC ACTGTACTCC AGCCTGGGCA 25 ACAAGAGCAA AACTCTGTCT CAAAAAATAA TAATAAATAA AAATAAAATA TTTATATACT CTGACCCATC AATTTGTCCA GCATAATTAG GCATGTGTAC AAGGGTTTAC ACACAAGAAT GCCTATTGCA ATATTGCTTT TAATGCTAAA AAAAATTGGG GAAAATGCTT TAAAAATATA GATTAAGACT GTACATTGTG GTACAGTCAT ATAATCAATA GTATACAGCT ATTATTTATT TTCAGCCACT GTCCAAAATA TAGCCTGGCC TAACAACATT CTG'TAGGAT ACGCAAGCAC CGTGAGGAGA TCAGCTATAA AGTATCAGTG TTTCACACCA CTGCTCCTTT 30 GCTAATAACC TTCAATGGCT TTTAAAGAAG TAAAAAACAA AGGCAAAATT CCTTAGTCAG CCCTTAAGAC TCTCTGTTAC TTAGCTCAAA CTACCCTTT CAACAACACT GCCCTAACCA GGATGAGTTT TTTGCCCCCC TGGAGTACAT TCAGCCTTTC CTTATCAAAC CTTCCTTTAA ATAAGTATCT TCTCCAGGAC CACTTCACTT TCTTCCCCAA TTTAGCATTT TCTATATCTC CAGGCCTACC TCTATAAAGC CTGTCCTAAC CACTCAAACC CTAGCVTT CTCTGAACTG CTAGAAATAT TTCTCTCA TTGGCCAT AGGTAAAAAG GTTTTTACTG 35 TTTATTACCT ACTCAATAAA AATTTCTTT TGAGACA AGGTCTTACT CTGTCGCCTA GAATGGGGGG AAGTGGTGTG ATCACAACTC ACTGCAGCTT CTACCTCCCA GCTCAACAGT CCTCCCACCT CAGCCTAGTG AGTAGCTGTG ACTACAGGCA TGTGCCACCA TACCCCACTA CTTTTCATTT TTTATTTT GTGAGATGGA ATCTCACTAT GTTACCCAGG CTGGTCTGCT GATCTCAATT GATCCTCCCA CTGTGGCCTC CCAAAATGCT GGGATTACAG GCATGAGCCA CAATATCTGG CCCCAGTAAG CTTTTAAGGC CATTAACATG AGGAACAGTG 40 TTCTACAC TATITTATCA GCTAGGGCTT TGCATGGAGT AGGAGTTTAG TAAATGCGGT TGATGGGTTA ATCAATGTGT GAAAATATTC AGAGCCACCA AAAACAGATA TTATGTCTAT TCTCATCAAC AATCAAAATT GAGTAAACAG CCATTTTCTA ATACAGGAAA CCACAAAACA TTGAATGGTG ACATTAAAAA ATTCCCCCAG CAGGAGCCAA CCAATTTTTT CATCCTGATC CAAGTTAGCA AACTGCAAAA GATAGGAAGC ACTAATGAGT GGAAATTTGA GTAGAAGCAT TTCTTATGAA GGCTGTCTTG ACTGGATCAC ATTTATTG CTGTTGGAGG 45 TGCCAAATGT GTGTGTTTAT GCTAATCCTC CACCTCAGGC AACACACAGT CAAGGATCCT ACCAAGTGTT ACCGTCAAGT GTCTGTTGGC AGCTCAAGGC CCCAGCGTTG TTCCCTTGCA CTAGGGAAAA GACATATTCC AGGTACAAGT ACTCCCACTT TGATGCTACA GAGGAGTTGC TGAACTTrGT GTCATTAATC TCTCTTCGTT AGATCCCAAC CCTGTTTAAA TCCCACTATC TGCCTACTCT GGGTCTTCAC CAATACTA GATCATAGTT GGAGAAAATC TACAAAGCCT TGCTCCCTTT AGATTTAAAC AGGTCTCCGT TTAAATTTAG AATTGCTAAC 50 TTCAAGCGGG CCCTATGCG ACAGTATGCC TGTCAGTCAT ACTACATTTC CTCAATTCCA TTCATGTGAC TGCTCCATAC CCTTCCCTCT CTCTTCATAC TACTATTATC TCTTCCCCCC TCCCTCATTT TTAACTGATG ATCTTGTTTC CTATTTCTCT GAGAAAATAG AAGCCATCAA AAGAGAGTTT CCACAAACTC CTACTGCCTT ATCTAGCCCT GTACCATATA CTTTGCATTT CCTCTCATTA CCATGGATGT ACTGCCTATC TGTGCTTCTA TCTAAGGCTA ACCCTTCCAC TTCAGTTTTG AATATTATCA GCTCTrACCA ACTCAAGGCC ATTGCTCTAG 55 CAATTCTCTC ATTCTCTCTC ATTCTTCC ATCAAGTT CCTTTCTTC AATTAACAGA GTAGCTCCTA AAGGGAAAAA AAAGTCTTCT TTCAATGC TCATCATCAC TGGCCATCAG AGAAATGCAA ATCAAAACCA CAATGAGATA TCATCTCACA CCAGTTAGAA TGGCAATCAT TAAAAAGTCA GGAAACAACA GGTGCTGGAG AGGATGTGGA GAAATAGGAA CACTTTTACA CTGTTGGTGG GACTGTAAAC TAGTTCAACC ATTGTGGAAG ACAGTGTGGC GATTCCTCAG GGATCTAGAA TTAGAAATAC CATTTGACCC AGCCATCCCA TTACTGGGTA 60 TATACCCAAA GGATTATAAA CAATGCTGCT ATAAAGACAC ATGCACACGT ATGTTTATTG TGGCACTACT CACAATAGCA AAGACTTGGA ACCAACCCAA ACGTCCAACA ATGATAGACT GGATTAAGAA AATGTGGCAC ATATACACCA TGGAATACTA TGCAGCCATA AAAAATGATG AGTTCATGTC CTTTGTAGGG ACATGGAGGA AGCTGGAAAC CATCACTCTC AGCAAACTAT CACAAGGACA AAAAACCAAA CACTGCATGT TCTCACTCAT AGGTGGGAAT TGAACAATGA GAACACTTGG ACACAGGAAG GGGAACATCA CCCACTGGGG CCTGTTGTGG 65 GATGAGGGGA GTGGGGAGGG ATAGCATTAG GAGATATACC TAATGTTAAA TGATGAGTTA ATGGGTGCAG CACACCAACA TAGCACATGT ATACATATGT AACAAACCTG CACGTTGTGC ACATGTACCC TAAAACTTAA WO 00/62736 PCT/USOO/08020 170 AGTATAATAA AAAAATATAT ATATATATAT AAAACAACTA AAAATAAATC 'ITC~TTCT GCAGGATCAG TCCATCACCA CACACACAGG CTGTGTITA TGTrGTTCCC CAGCTT1AAGA GATCGTT1CTC CAGATCCCAC TGCTCCr'rCC AG F7GTCACC TCAGT-rCTCC ACTrCTI=r GCTGATAAAC TACTCTAACT AGTTACATAT GATTTCTGTC CCCAGGTCCC CTCCCTCAGT TGTITTGAAC ATAATCATTT ATATCATrA TCATTCAC 5 TCTAATTGCA CAACCAAAAA CTCCCT7 TITAGATGG AGTCTCACTC TGTCACCTAG GCTGGAGTGC AGTGGCATGA TCTCGGCTCA CTCCAACCTC CGCCTCACGG GTTCAAGTGA TCCCCCTGCC TTAGCCTCCT GAATAGCTGG GATrATACAC ATGCACCACC ACACCTGGCT AATTGC'I=G T'TI1GTrG TGTGTGTGTG TGT'T'Tr TITI1TGGA CAGAGTCTCA CTCTGTTGCC CAGGCTAGAC TGCAGTGGCA TGATCTCAGC TCACTGCAAC CTCCACCTCC TGGGTTCAAG CGATTCTCCT GCCTCAGCCT CCCGAGTAGC TGGGACTACA 10 GGCATGCACC ACCATGCCAG GCTAAfTTM TTGTAT=TC AGTAGAGACC AGGTTTCACC ATGTTGGTCA GGCTGGTC'IT GAACTCCTGA CCTCAAATGA TCTGCGCACC TGGACCTCCC AAAGTGCTGG GAI17ACAGAC TGAGCTACT GCGCCGGGCT AITIGTGTT 'ITAGTAAAG ACGGGG=TC ACCATGTrGT CCAGGCTGGT CTCAAACTCC TGACCTCAAG TGATCCGCTC GCCTCAGGCC CTCAAAGTGC TGGGATTACA GGAGTGAGCC ACCATGCCTG GCCATAAAAC TGCCCTI1TGT TAATATGACT GTTGGCCTGC ACATTGTCAA ATCCAGTGGC 15 ATTCATCTTA CTCGGCCAAC CTACGGCATT TGACACTGTC TGTCTTTCCT TCTGTTCCTC TATCTGTTTC CAGTATACTG GCCTGGCUT CTTT=ACCT CTrTATATG CTCTTCCAGT CTCAGGCTCC 1TTGGGGATT TGAAGGTATG TTGCA'TTFTG CTATTCAATG AATAATGACA AGTAATGATC ACPI'AAGACA TTAAGTGGTC AGTTCCTITA CTAGGATAAA AATAA=IIC TTCCCAACAT GGGGCATATF CCATITCCAG TCTGACTGTr CTGTGTAATC '1TTGTATTCC TTGGCAGCCC CTF1ATATC AGTTCATCTA CTGTGCAGGA AATTGGACAA 20 ACA=IIGCAC TGGTATAACC AAATACAGT7 GAACTrTGG CTTGACTCTr AGCTGAACTC ACCAAAAATA ATTTCTGTAA GAGACTOAGA CGTCTACGAG TAGGTITIC AGAATTAGTA AACATAAATC AAGGATACAC AGGTAGATI17 GAATTTCAGA TAAACAACAA ATACTTI1 AGTATGTCTA CTGAAATATT TGTATCTTAT CTGGCAATTC TACCTGGTAC AGAACTAATC CA FrCTC'TFG AAAGATCTTG ACTCTGTAAT AAGYTTG GTGATGGAAG GGAGGTA'Tr CTGTAATTAG AGTCACTGTC TTCCTCCCAG TIT1TATCC TGGCCCAGAT 25 CTGCAATGAA CACACGACAG AATCCAGGGG GGATGAAGAT GGGTGCT7G CAGGAAAAAA AAATTAAAAA CATCTGAAAA AGC'TM1GTA CTAAAAGAAT GTGATCTAAA AAAGAAAGCA GGAGAACTTT CTGTCTGCAC 'ITTACATCAG AACAACCTTG GCGTCTAGAA GCTGTGCCCT GTGGGAAGTG GTGGTGCrFG GTAAGAGATG CCAGGACCAG TGGTACCCAC TGGGAGCACT GCCAATACCC AGCAAGGAGC ATGGGTGCAC AGTAAGGCAT TGCACTGTGA 'I1CAGCATAA AATAACAATA AGGGAACGTC ACGGAGAAAA GGCCAGACTT CCTrrGrJFTA 30 GAATGTGGGA AATGTCTTCT GAAAAATGGT AGTAAAAAAG CATGCTTGGA TGGTCCACTC CAGGCAAAAC TGACTAATCG GGGGTCAGGG ATACAACCCC TGCATCATAT G 1TTG'IMCT GTTGGGCTGA CATGAGGTrC ACTGTGACCA CTGTGG ITTA ACCCCATAGT CTCCTGGAAA TACAGCCAGG TCAAGAGAGC TCCACATAAA ACATAATCAA AAAAATAAAC TCAAG'1CC ACTGATCAGC TMTCACAAC TCTTATCCTT TCACTAACTT TGGAGCAAGA ITGAGAATT GGATGGCTAT TTGAGGGCTA TTTCTGCGCT TTAGTTCAAT GTITCT 35 TTC'ITTATTA GAGAACTATG GnT1TATTr ATA=IACAC 1TTAAGTTCT AGGGTACATG TGCACAACGT GCAGATTrGT TACACAGGTA TAAATGTGCC ATG'rTGG=m GCTGCACCCA TCAACTCGTC AT1TrACATTA GGTA T'CTC CTAATGCTAT CCCTCCCCCA GTCCCCCACC CCCCGACAGG CCCTGGTGTG TGATGTTCCC CTTCCTGTGT CCAAGTGTTC TG'ITTATGTG ATAGATTACG M1ATrGAT7 TGTGTATGTT GAACCAGCCT TGCATCACAG TCAC FrGCTrr ACAAGAAACA AACACTTCAC AGATGGATCA TTATGTGTGA TAAGTGAAAT 40 CCAAGGATTT ATGCTCAGAG GTGGGCTrAA CAGGTAGGAA GAGCAGTATr TrCCFrCAAC CATGAGTGTA TGCAGGTTTT TCTITITT 'FITGAGATGG AGTCTCACTC YTTACCCAG GCTGGCGCGC AGTGGTGCGA TCTTGGCTCA CTGTAACCTC TGCCACCTGG GTTCAAGCAA TTCTCCTGCC TCAGCCTCCC AAGTGGCTGG GATTACAGGC ACCTGCCACT GTCTCCGGCT AA'TrGTC 'ITrAGTAG AGATGGGG~r TCACCATCTT GGCCAGCCTT GTCTTGAACT CCTGACCTCA TGAATCATCC 'rrCTCAGCCT CCCAAAGTGC TGGGATrACA 45 GGCATGAGCC ACTGCGCCCA GCCCACAGGT 'FT=CAAAGA CTAAACTTAA AAAAAAAAAA AAAAT-T~ccc AATGAAATAT AAAACTAAAG TGCTAAACTG TGATAGACTG TnITACAAGA ATGCCAGMT TCACAAGTGT CTATAGAACA TGTAATTTAG ATAGGTAAGA TGAAATPTG ATAATATT1'G ATGGCAAA'IT TAAACAGGTA TACAACAAAA ATAAAATTCT AAGCCCCTCA ACCAACTGAA TGGACTCCTT CTCTCAGCCA AAGGAATACC AAAGTAAACC TGAAAAACTA G=IrGGCCA GGA'ITGGGGG TAGGTGGGGG AAGCCCAACA TGACTCATrA 50 TTCTCTCCTC CCTTTGGAAT TCAGGCACAA CTGAATGTCA GCATTGACAC TAAAACACAG ATCTTAAGAC TGACAAGCCA GACTC'ITrGT AGCAGAGAGC CAGGCCCTGG AAGAAATCAA GTI7AYIAT CCCAAAAAAT ATTTC''GA TATAT1TCA AATGGCCCTG CAAAGCTGTC TCTTGTGGGG AAAATTGACA TGCTGTACAG ANTWCCT-rC TCTI'CCAAG TI1IACTGA TCCAGGAGAG ATTJAACTAA GAGGCTAGCA TGTTrT'1 Tr17TTTTT TGAGGCGGAG TCTGCTCTG TT1GCCCAGGC TGGAGTGCAG TGGCGTGATC TCAGCTCACT 55 GCAACCTrCG CCTCCCGGGT TCAAGCGATr CTCCTGCCTC AGCTTCCCGA GTAGCTGGGA FrACAGATCC ATGCCACTAT GCCCAGCTAA TflTGTAFT TY1GTAGAG ACAGGGTTrC ACCATGTJGG CCAGGCTAGT ATTGAACTCC TGACCTCGTG ATCCGCCCAC CTCGGCCTCC CAAAGTGCTG GCATTACAGG CGTGAGCCAC CGTGCCCAGC ACAAGACATT TACCGTCTAT TCTCTCTGAA GCTACTATCT AGAGGCTTCA TCAACATAAT AAGACCCTI'G GTCTCCACAA CTCCYI'ATCT TATCCTATTA G TI'TCTACTG A'ITCCAGGTC TTTAGATAAT 60 AACAACTCTT TCAACCAATT GCCAATCAGA AAGTCTTGA ATCCACCTAT GAC'I1TAAAAG CCCCACTCCT TCAAGTTATC CCGCC'ITTCT GGACTGAACC AATGTACACC Tr~ATATGTGT TGATGGATAT CTGCCTGTAA CT'rCCATTCC CCTAAAATGT ATAACATCAA GCTGTAACCC AACCACC117G GGCACATGTT TI'CAGGAACT CATGAGACTG TGTTGCAGAC CTTGGTCACT CATATTTGGC TCACAGTAAA C'rrC1TTAAA TAYTGTATAG AGTTGGCTT TTrCATTGA CACAGGAAAA ATAAAGAATr GGAAGGTCTT TCATCAGTCA CTGAGCCAGC 65 TTCATATCTG ACTGAGGTCA TACAGTTCAG TGA'IMGTAG C'1TTGCTACT TAGATFGCTA TCCATrATCT AGAAGCATCA GGATCACGTG GGACCTATTG GAAATGCAGA CTITCCTCCT AGAACCCAGG ACCTTGGAAT WO 00/62736 PCT/USOO/08020 171 A FrCT'FGGCA CATAGTAGGT GCTCAATACA TATTGAACTC CTAGGTGCAA TTCATTAATT CATGAATTAA TGAATTAACA CGCTCTCAAA G1TAGTGCT T1TCACAGA CTAGTC1TC TGCCTCTTAA GCACTCAGCT CACCACGCTT1 CCAGTCTCAC TCCCCTATT1A GTCTGATTAA AATCTGCTTA CATGTGAGTC TGAGATCAAG TG'ATCTCT TCTGAGAAGT CTTCCCTCAC TGGCCCAAAG GAA=rCTCC TCTA=hIAG CACTGTCCCA 5 GTTGAcTrGT CATh'ATTCTA GTCTI=CA TATTAG TrGT TI=CATATA TATGTI'A'TA AGGAAACTAG TCA=TCCCC TAATAGAACA AAATTGCTGG CCnI7GGGGT TGGCAATGGA GGGGAGGCTC T-rCrTGAAAA GGGGGAAGAG TGI17CTCCTA ATATI1TCT TACGAGA'ITT ATGTrGCTCA TC'ITTAGCCT ITrAGTCCCCC ATTGCCTGCC TACAGTTGGC AGAGACCATC TGTTCTCTCA CTGTCAGGAA CTGTCTCAAT TCTTGAAGT-r CAGAGTCAAA AAAGAAGCAA GTIT~CCTAG CTCITGATC AACTFTCAAA GTI=ACTTrC CATTGAAAA 10 ITTTACTAAGT CACCAGGAGA TGG'TrATAC TGAGAAATAT CCACTCATAC TCTTCCTC'IT CAACTTTCTT CCATATACAC CCTATFTACAG GGATATAGTC TTFACTCTATA GCTCAAAAGG ATGACCCTAT CAGAAACCTG CACAGTATGT AAAACAYI7CT CACCAGAGGT TCACTrGTGT A TTCCACCC TAGAATGGAA GCTCTACAAA AGCACAGAAT GTATCATITT AACTI1?AGAT TCTA=hICA CACCCAGTGC TTGACACATG ATTTGAAGYF AATATATT TATCAAGTGA TTGTMTAAA ATCATGACTC ACTCAACAAA GTTATAAGAA TAAGAATAGT 15 GTTACAGAAT TGGTATACAC AAGCTGACCA TAATCAACAC ACCTATTATC ATTEFT1TrGC GACAGGTTCT CGCTGTCTCA CCCTGGCTGG AGTGGAGTGG CATGACCACG GTTCACTGCA GGTr-rGAACT TCCAGGCTCA AGCAATCCTC CCACCTCAGC CTCCCACATA GCTGAGCCCA CAGGTGTGTG CCACCATGTC CAGCTAACTT TTTAATTCTT TGTAGAGACA GGGTCACCCT ATGTrGCCCA AGCTGGTCTT GAACTCCTTG GCTAGAGAGA TCCTCCCTCC AAGGTCCCCC AAAATGCTGG GATCTCAGGC AAGAGCCACC ATGCCTGGCC ATAATCAATA 20 CACT'ITTAAG AATGCTAGAA TGTTATATCA GATGCATACT TCAGCACTAT CTCAAGCAAA CTGGGGTGTG GG'FrATTCTA CATATAAAGT TCAGCAGTGT TGYTCCACAG TCCCAAACTC CAACTGAGGT CAAATGTAGG GTGCAGCAAG GTCACTGGGG CTGTCATCAA GGGCCTCTCC TTGCACTCTT GCCAACCCTG TTTCTTGA'rr GTCTCTACCA CCATGAGTCA CCAGCAATCT CCCACAGTCA CTrGTrrAAA AGTTCACAAG TATTGTGTGA ATrGCAGGCA ACCCCTTGAC TCCCTGATrG CCTGGTCTTC TTCCYrGGGC TCTACCAT[T TITTTCCCCA 25 GCACTCTTTC TGCTGCTCTA AATITTAATL1 CATGCAATTC CATATGTGTT TCTCTATCAT TCTTCATCTC TTTCCTCTCC CITFCCATCCA A FP=GTITG TCTGT7FGCT TGCT1GCTG C'ITAATACA '1TCTCTInr TCTGAGAAGG CTTGAGTCCA AAACTCTCAG T7ACCTG ITG TrCTG'I=CC CGTJ7AG'ITAA TCTCCGAACC TTCATAAAT'r AAATCTGACA AAGTCCCCTG ACTAACAAAG GAAATGCACA AGTCACAGTA AAAGGGGCAC ACACAGAACA CAAATAGACC CAGGGTC'= TCTGTTCATC ACTCAGCTIT 'ITATAGGAGA TCCAGGAGAA 30 ATGAAGTGGA AAGGGAAGTG TGTTGAGITFA CTATACAACA CAAGAGTAAA CTTTCTTATA AGTGGTAATT FTITACA GGAATAATI'G AAAATGGAAA TTACCTTCTC TACTCATAGT AAGTACTCAG TGCGTTCTTG ATGGGATGAG AATGTGTTTG AGCTIAGTG TAAGGCAGAA TTCTGTrrAG TCTGCCAGTA FrGGAGAAAA ATAAAACACA AAGGGACTGA CATGTAGGAA GTGGCACCTG GGAGGGTCTC AAflCTrCCT A'L1ACAAAAA TGCCCCAGAG AAATAAAAAG CTTGTGTACA TGTTGAGATG GGAGAGTTCT CTGGCCCCCC TCGCAGGATG 35 TGTGACAGTG GGGTGGCTCT CTGCTGCGCC ACCATGAGCT CAAACCCCTC ATAGGAGGGG GAGCACACAG GCAGGAAGGT GCAGGAGCTG GGCGAGCTCT TTGGGCTCTG GCCCCGTGGT ACTGTCTAGA GGTGGGTGCC TGCAACTCCT GAAAGCCCAA GTGGGCATGT G2FTACAGTGC ACTC'ITTCAG CTT11GCTGTC TGCAGCTFTAA GCGTTAACCA GCTCAG'TTfC TTCTTGGTAC CCAGGTCCTT GTCTGGCATC CAGGAAGAAT CAGGTTACAC ATGGACTTGA AGGATGAATG TGGGAG=II ATGGAGTGGT GGAGGTGGCT CTCAGTGGGA TGGATGGGGA 40 GCTGGAAGGG GGATGGAGTG GGAAGATGAT ATTCTCCTGG AGTITGGCTG TCCAGCAGCC GATCTCCTCT CCAGTCGTCC CCAGCCTCTC GACGTTCAGA TGCTCCTC'IT CTCTCCTTCT CTGCCATGCT G'FrCTGCCGT TCATCTGCCT GTCTCTCTCT GGAGCCTGGA A'TrGGGGTT TATATGGTAC ACAATAAGGG GCATGGCAGG CCAAAAGGGA AC'TTTAGG TGCAAAAAAC AGGAATGCCT CTTCTCACTT AGGGCTATAG ATMTCAGGC TTGAAGGTGG GGCCTTTACC AGCGAACCTG TA=TCCCTG TCTCCTGTGC ATATCAATGT AATCAAATAC 45 TGGGCTGATC CAGGATG'Tr CTTTAGACCA A'ITATGGGTA AAATAATITA CAI17CAGGTT 'TTATATTTG CTITTGTCAT FrC'TrMAA GCAATCATGT AAAATATCTA TACGACAGTA ATAGATGATA GCGAACCTAA TrAAAA'rrAC CAGAAACTTJA AGAATCTCTA ATGA'TTCAA CTGTAACTAA GGTTA'TTCT C ITTATGTTG AACAATG11'G GGAGATAAGA CACAAGAGTI' TCTGAAGTAT TTCAGAAACA CAAAGAGGGA GGTTATATAA ATAATATI 'TTCCTACTF TGGGAAAATG AAAGCTAGTC ACAAAGTTAA ACGAGTGGTT A=h'AATAT 50 T7AAAATACA GGCTTGGATG TATCCTGT TAAAGAAAAT AAAATGCAGA ATATTCAAAA CGTCTGACCA CCC'ITCTAAG AAAATGCATC TCTGAGGTAT ITICCTrAG AAGTTATTGT AAAAATCCTG GAGAAGCTTG AACACAGCAA AGCAAACAGG ATGCAGAG'IT TAATCTGTGG AAAGCTTAGG GAAGAAAAGC AAATCATrTAA AAATAGGTCT TCCTCTGAAG A'TITAAAA CGCAAAGAGG GTGGAATAGC AATGATAATA AAAAAGCTGG CATAGAGAGT GGCACAATTT GCTGTGCCAC TGAGCTGACT GGATGTGTTC TGAAM~CTA GGCATITAGTG 55 TACC'TTCCA CACGCATTCT CCC'ITTAAAA AAAATGCCCA CACACTGAAT ACTTT=TCA TGCAAT'JTAA AATAAGCGCA CCATCTAGTT TACAGAAATT CACTAGAAGT TATrATCCT AAAATAGCAG AGATCTAGAA GAATITGAG CTCTAGGACA ='TAGACAC ACAGAAAGAA GAATCTGGAC AAGTCTTGAC CAGACATGAC AGAATAGAAA TTTCT1TCC TATITATCTC TTIGAATAAA ATITfCAGGA TCTTACAGTG GACAAGITTG FTATCTACAC ATTGTGAAGC ACATTGA TT CTCCTCTGTA GCCT7AGGAA GATCTGAGAG GTGACTGAGC 60 TGATTGAATG ATCCGTGACC GCTCTACTGG GACCAGTAGT AGAAC'TrAC TGGTGGAGAC CTGCTGGAGG 'ITTGAGAGCA GACTTTGAAA A'ITACTAGAG CTACACAGAT ACTGTGTGGC TAACTGGATTF ATG'FITAGAG GC'TrFCAGAA CTATGCTGCT GCTGCTGCAG TGTAGCCAGG ACGCACAGAG AACATCTAAG GCTCTGAAT GGGGCGATAG GGACAGATTT CAGCAGCCAT CTGAC'ITCAG TGCTCATIT GATGCTT7CC CTGCAGGGTG CAGTGTGCAG TGTGCAGTGT GCAGTGGTGG GAGGCTCACA CAGGAATACT TGCTI7CTGTA GCCCTAATIT 65 CCGGTTCAAA CTCTGCATTC ACCTTGACAG ATCTI'TCCT TGGCCAAAAT TTAGTTAGGC TI7CTGGGCTT TCTCTTATGC CCACCTGCAG ACTITTGGT AAAATCCAGT ITFTAGTAAAG AGCTCTGCTA AGTCAGTI17A WO 00/62736 PCT/USOO/08020 172 GCAAGAATCC CCACCTCAAA AGTCACTATC TCCCTCCCTG GTAGTGTCTG GC'FrGTC'rrC AGCGAGAATT CTAT'FAGGTT CTGTFAGATF AGAATCCTCC 317ACCC'ITGA TGCTTCCTCT TAGTATIT= TCATCCACTG ACTCCT'rGAC CCACCTTGCT CCTCGGCTAT AAA'ITCCCAC TTGCCCATAC TCTGCAG'rrA AGACTA'ITr CTCCCCACTA CTGCAAAATC CCATFGCCAT GGTCCCTATA CTATCTCAAT GGTAATGAAT AAAGTCTGCC 5 TrACCATGCT T-FIAACAAGTA ACATI'GAACC AnTTTCT 1TAACAATCT GCTGCACAAT GAGATTACTA AAACTrA'r CCATTTTGCC ATGCTGGATG TCCTCAATGG AATGGCTC'IT GTGAGCACCA AATCATTGTG AGAAGGAAAA CCCATCTCTT ACAGCCCCGT GTAACGTGAT GTATGTrACA TGTGATGTAT G1TACATAGT YITI1TCAT GTrGATCACT TTTTGCCCAT T[TCCTATAT CTTATCAGTT GGAAGACTGT GGAAGTGT AGTACTAAGC CACAAGATGA CTAAGAAGAG TTGAAAGGGC AAGTGGGGCT AAAAACAGAT 'TrGTITGAC 10 TTACCCCACC ATTCCCCCTA TCATGGGGCT GAATCTGCCT GGAGGAAGGA GCATCTITAT CTI17GTACTG TGAACCACAC AGTCTAGCAG CAGCACAGCC AAGGCACTTG GGGTTCATG AGACTAAGTA CATGCAATTC TAT1GTAAAG GCYI7AAAATA TATACAACTG ACCC'ITGAAC AACATGAATr TGAATTGCAT GGTCAGTTAT ACGCAGATIT TCTCCACCT CTGCCACCCC TGAGACAGTA AGATCAATCA ATCCTCTTCC TCCTACTCCT CAGTCTACTC AAAGATACT? GAAGTCTACT TGAAGATGAC AAGCACAAAG ACA'TrTATGA TGATCCACTT 15 CCACITrAGTG AATAGTAAAT ATGTITCTC TTCCTCCTAA 'TTrIAACA CTTTCTTCTC TCTAGCTTAA ITrATrGTrA AGAATACAAT CTATAATACA TATGACATAC AAAATATGTC TTAGTITGACT GMTATGTrA TCTGTAAGGC I1CAGGTCAA GAGTATGCTA 'PTAGTGGTTA AGTMTCGAG GAGTCAAAAG GTGTATGTGG ACYJTCAACT GCAGGGGGGT GGGCACCCCT GCCCCCATGT TGTI7CAAGGG TCAACTTTAC TGCCAAAGGC AAGCCTTrAC ATCCACTTTr TCCATCCCAT CAGTAAATGG AAAAAGATAG CTACAGTATC CCTGCGTCAA 20 ATC'TTITT TTGCAGATCA CAAA'I1GGCC ACTCACC'MG CTCTGTGAGG GGTAAAATGC CCCAC'TrCT T[AGTAATAT TTAAGTTAGA TAATATITAA GTTATAAAGT TGTFCTTTGT AATCGTTAAT TGTAAYTT' ACATAGTrC 'TrCAAACAG AAATAGCATT MTGTTAGAT AACCTCCCGT ATAGATGATG AAACTCC'rfr TAAGGGCTAT CTGAAFT = A A'ITCCTTGAA AAGGCAGAAA TTGGATAGCT AGTAGTCATA AATGTACTGT GG=rCCCCC AACCATCTGG GCTATATAGA AGCTGCATCC 'TGGACTGCA GTAGAGGAGT CTTACAAAGC 25 ACAGAGCAAC TTCTCTCCTG GGI17GCGCTA GTTATGATGG CAATITrAAA TGTGTAC TT TACCCAAAGA AAATCC'I1AT TATCAACAAT CACAATGCCA TCATAACCAT GGTATAAAAA ATTCAAAATG TCCCAGCTGA AGTGGAGGCA AAGACTCAAG TTCATGGAGT CAGAGTTTCC 'rTGCTATTCC TCITTCAA ATGACCA1TI AGTAAGCACC TGAAGAAAAT ACTATGGACG GCATTGAAAA GTGAAGATAG GTTTAATCTT CTCGAAAATC TAAT'rCTCCA GATGAAACGC TGACACTTAT CCACCCCACA GACCCTATAG CAGATGTGTC ACTGGCCATC 30 ACATIGACA CAGAGAAGTC ATAACTCAGT CAGGACAGAG ACATEI'CCAT GAG'ITTCTGA ACCATGGACA GAACGTCGTC TGTGGGACAT GAAAACTGGA ACTrAGAGGA CAGGCACATC TGAGAAATGG GCAGFI17AAA GGCAGAACAT AGCACATATG TGACTGGG'rT TTAGAAGCAA ATTTACAAGA CGCACTCTTC TTCATCCTAA ATAATCTGCA ACCAAAGCTT CCAAAAAAGA CAATTTAGGA ATGCAGAGGT GAGGAGTAGG GAGGGGAATG GGATGAGAGA GAGTGGAGAT TAATGGTGGG CAGAGCGAGG TTAGAACTT AGTGGTTTCT TCAGGTTCTG 35 AACTGAAATT TGTATACTGT AAAGGCACAA ACACCATIT TAACAAAAGT GAGGAGGACT TCCTATCTGG TTrCAGAAAAT AGGTGAATAA ATAGTACGAA TTATTAAAAA TAATAATTC CACTTATACA TAGGAAA=t GATAGGAACC ATGATAAATG C FAACTCTT AATCTrCAAG GAACTCTGCT AGGGATATAA TATI'ATAAAT CTTGTThJTGC AGATGGAGAA ATTGAA ITI AACCCAAGTT ATCATAACCC TTAAATGAT AAATGATACT GTrACATGAG AAAGCTGCGT ATCTG1TJCC TGGAMTGTA GCCATAATIT GTGTCTCAAG TCCCTTTTGC 40 TGCCAGCTAT CTGGGTAGG TGTGTTCCCT TT1GGGCTG117 TGATACCCCC ACA'TTTATCT TTfTTT=C TCTTTT=G TTGAGAGAGT CTTTCCCTGT TGCCTAGGCT GGAGGGCAAT GGCGCGATCT CGGCTCACTG CAACCTCCGC CTCCTGGGI1 CAAGTGCTTC TCACGATTCT CTTGTCCCAG CCTCTCTAAT AGCTCGGATT ACTGGCATGC ACCACCACGC CCACCTAAT TTGTAnfIT AGTAGACAAG GGGTTTCTCC ATGTTGGTCA GGGTGGTCTC AAACTCCTGA CCTCAGGTGA TCTGCCTGCC ITrGGCCTCCC AAAGTGCTGG GATTACAGGT 45 GTGAGCCACC ATGCCTGGCC CCAAATI1AT C=hAATGCC CCAAATTATC TAGTTCCCAT GACTGGGCTT CTGCMIIGAT CCTrCTGCA CTJGCTGGAC CCTCTCCCTG GGAAATGAGA 'I1GTGTCCTG AGCCCCTAGT TAGAGGCTAT GTCTCTGCTG TTCCTGAATG GGCCTCCTGG ATGAGACCTC ATTAAAAGTC TAATrCTCTT GGAGAATTGA GAGATACCTA T'YrGTCTCAA AATCA I1GAA ACCAATTAAT GTAL17ATGAG CCTCTATCCA GTGATTTGTA CCTCAA FTCC CCAATCCAGC TGTCAAGGCC AATITGTTCT ACCTTACCTA GTAGGTAAGT 50 CTGGAATTGT AGCTGTGGCA TITTrCAGTAA TGGTACTCTA GGTTAGCAGT CCCCAACcTT 'TTGGCACCA GGGACCAGTTF TrGTGGAAGA CAATEITCC ATGAAGGGCT GGGCAGGGGA. GTGGTICAG GATGAAACTG TTCCACCTCA GATCATCAGG CATTAGATTC TCACAAGGAG TGCGCAAGCT AGATCCCTCA CACATGCAGT TCACAATAGG GTGTGCACTC CCATGAGAAT CTAACACCGC TGCTGATCTG ACAGGAGACA GAGCTCAGGC AGTAATACTC ATFTGCCTAC CGCTCACCTC CTGCCGTGCA GCTCAGTI7CC TAACAGGCCA CGGACCAGTA 55 CTGGTCCACG GCGCAGGCAT CAGGGACCCC TGTTGCTAGG TATAAGCATC TGGCTGCTGC ATGTCTTCTG TGTAGCTACA TCTGTATGTG TATCTGATGA GATATAAATI' ATJTGATTAT AAATTACTrT CTTCATATTA GAGTTGTGAA TGAGTATCAC ATATAATTAT ACATAAACTA GGAATATGCT ITrAATAAT GTATATAAGT AAGT=CCTT AACTATGACT 'rCATCTTAG CGTAGTAAGA GGGTGCTAAG AAATATTTGT GATGAAAATA GGCATrGGTA GAGTrGAGAC CACTGGGTGA TGAAAGAGTG TAAAGATT AAAGCCTI'CA GATGCTGGTr 60 CAAGGTGAGA AATGTGATTG GGAGCAAATC AATTAACTTC TTGAAGTC1T ATAGGGCAGT TATGAATACT TAATGTTAAC ATATGTAAAG CTCMCTGCC CTGTATACAG TAAATGCTAG TTAGCTATTA TGATCACTAC TAAAATGGGG ATGACATAAA CCTCATAAGG TITAAGTAT TATGCAAGAT ACTATACAAA GTCCAGTAAA TATCACATTC AATTGAATCC ATGATGTCCG ATrA=mAG CTAC'TCCAA GAGAGAAAAA AATGCTGTCA GYTTACTGT TC'ITATAGAG AGCAAGGCAG ATCCCAATTC CCAATGTGGT AACGTGAAAA TTTTGCATT 65 TGAATCAACA AAACACT-C TCC1T'II CCTACTATr AACAACTGGT AAGTCTATAC TCCCCCAAAT CTGGAATJ7CT CCTTTCTTAT TCI7CCT CCTACCAAGA CCGCAGGATC TTMACTT1GG CTATAAGGGG WO 00/62736 PCT/USOO/08020 173 TAAACCTCAA GTAGTACAAG TT1CTGTGTAT TACTITTATA CTCTGTCACA GATrCCC'Tr GTrTCCTCAT CTCCATGTGA AITTAGTTAA ATTICTCAGCA TTCTGATCCT TACTATACAA GGTAAATGAA TATAAAAACA AAACGAAACA AAAACCTCTT CCTATTTACA TAAGGCCCCA ACCTAATATT TAGTGATATA TATTAATGTG AACAAGGAAC TAACGAAGAC TGGGAAGAAA TTCACAGACT TGAGAGAAGA AATGG3CAGGA TTTCCTGGGA 5 ACAATPFCAT GTAACGTCAA AGGTGGTAAA AGGTCAAATA GAATGAAGAT GGAGAATACC GGATI1TTCTT ACAAAATGAT ITrCCCAGGAG ATCTCATCAA ATGCACGAGG ATACCT-rCTC AG'ITTCACCT AGTGAGTAAA AGACTGGTAA CATAGCTCAC TTACAA ITTG GATAAACAAA ACTAAACAAA CAACATCAAA A LTTCAGAAA AAATAATAGC AAAACAGAAA TCAAACACTC AAATfITGG TCCTTCTG'TF TA TrCA'TrT TGGATACTCA GTGAATGT'A ATI'AACCAGG AAACTTAAAA GTT1A TrCAA TTATGAACCT CTTCAATCCT TCATCAA FIA 10 T=FGAGTAT TCTGGTCTTA AAAACATCTC TTTCTTCTAC AAACTTCTGA AAGAGATGAA CACCTCCACC TACACCAAAA TAATGTGCIT TGCTGGCCAA AAGTACACGT CCA'rTrAC TT1AACAGTCT AAGGAAAGTC TGGTGCAAAT TACTATAATA ATCTGGGTT1G TAAATGGTh[ CTGAGGTGAG AATGAGATCA TAT=~ACAA AAAGTITC ACTAC FTAGT ACAAGCTTAC AAAACTCAGA CCACTCACCA GAAAAAAATC GGCATrATA TAGTrGTGTT1 ACTTGG'rr TCCTGCATCT 'TrTCACATCT GGCTCATI'A CATCATTTTC TTCATCTTCC 15 AAAGTGGAGT TAGCTACTAC ATlAGGTAAG GTnACITCAT CAATCACCAT ACTGTTATAA TCTGAAAGT GAATTICTL1 GGACCCTCCC TTGAATGCAG TTATACCTAG TAAACCTGAT CCACAACCAA GATCCAAGAC nFVV=CCCA GCAAATTTCA C'IMGGCC= TGTGAAATAA GCCAGGAGGT CAAAGGTACA TTCCCAGATT TITAAGCCTC CCTCATAAAC ACCTGTAATC AGATCAGAGT GAGAAGAAAA GCTJTTGAA ACTATGT= CTCCAGGGAA GTTCTCTTTC AACAAGATGG T1TCACTAC TGATAAC'ITA ACATGCTGGA AACCTGGTAA 20 TGTITICTATG ACTVTT CTAACATCTT C'TTAAATCT 'JTAGGCATAG CATGCTCTIT GGCAGCTCTC AAGGAGGGCT GTTm1CCATG TGGCTCCAAG TTCCTTGAAC TGCTGGCTGC ACTGAGTGGA CTGTCTGTGT CTTrGAGAGGG AGCTGCATJT TCCATTGACT TATGTTCCCA CAAGTGATCC TGAGGCAAGT CAAATrTGTTC TGCAGAACAT TTCTGTCCC TCTCT7CTCC TITIGACT TCTGAGACTG ACAGCTC1T TGAGGAATCC AGGGTCAAAG CTCCATCTCT AATGGGTGTI' AA FTCA TIT CCAGATGGTC ITCTATAGTG AAATI'AAACT 25 GAAAGGTCAT CCTCTTAT7A AATGCACACA ATC'TrAAAT TCAGATTCTI' CAACTI'CTGG ATAGAMTTTG ATGATACACA CAAATCTGCC TCAATTATTC AATTAG=T1 GTTGGGCCCA ATTTCTf= AGCAGCTTAT ACATGGTAAC AAATATAG AGATA TrCC AAATGACTT TTIAGACGTCT TrGGTCCTCT 'TTCCAAGCAG CTCTGGAAAG AAAAAAAAAA AAAAAAGAAA GAAAATGATG AT'FAAAGCAA AATGGCACAT TTCACTAAAG TGTAATATTA AACAGCCACC CCCACCCCTC CCTGTCCCAC CATACAGCTG C'ITI1?CTTA AAAAGTTGTG 30 GGGAAGAGAG AGAGATAAGA GATGGACA CTCATACACA C=TAAGGGT TCCAAAGTGG GAGAAGAAAA TCAACTATAA AAACAAACAG AAGAACAACA GCAACCACCA CCACTACCAC CTGGACAAAC ATAAAGTCCA AGATA FrCAG ACAGGACAGC CTAGCTACTT GCTGTC'IMC AGCTGTCTTG AMTGTGTCC AACCATAflC ACCCCCTAAG CTTCCAGAAT AACITCACTT CTGTCT=TA CAGAAGAGGT GCAGTATMT A'rT=GGTAA GTCAGCGTCC C'T1AAAAAC ATGCATAGGT ATGGCCTGGT GTGTGTAAAT TCATCCAAGA C'rCACTCCA 35 AACA'ITTAGT CGAGAACAGC AGCCCTAAGT GTATAGAAGT GGGGGTAATI' TGGCAATAAT TAGTAAAGAC TAATTCGGTG GCAGAGCAAA CGCAAACTAG GGCACTGCAG TAGTrTGGAG AGACCTGTAG AAATAAGAAG CAACTTTATT GAGAATCTTC TATCTACTGC GCTAGACACT ATACCATCTG CCTCAATI= CACAGTTCTG GCAAGTGGGA TC TGCC CMI~ATACAA GATJTACAAT TI7GGGGGAGA GGCGGGTCAC CCAGTCCCGC GGCTAGGAAC GCGCCTCn71 CCTCTCCCAT CACGCTGCAA GGCTTGGAGT CACTTCCGGC TGCAGGTCCC 40 GGAACAAATC CGACCCCAGA AGTGGGGACT TCTGGCCCTC ACCTCCCCAT TTGAATGTAA TG'ITTACAGT GATCCAGACC TGGGGATGCT TGCTTCCCGA CGTGTCCTGG GATCGCGCY7 CTGAAAAAGC TCACCTCACA ACGCCTCCTC CGGACCTAAA TCGCGCACCA GTGAGTCGAG TCCTCCAGGG GCTAGAGAAG CCCGACTTTC 'TCCGGCCT TGAGGGACCC GGGCTCACCA AGAAACCAGC CGCCCTCCTC TCTATGGMT TGGAGCCGGC GGAGAGCGCG CAAGGGTTGG CGGGACTGCG AG = CCGGT CTGGGC=TG GCGGGTCTGG ITGAAGCTC 45 TCCTGTTTGA CGAAAGTATG TCTCAGGAAG GTGCGGTCCC AGCTAGCGCG GTFTCCCCTGG AAGAATTAAG TAGCTGGCCA GAGGAGCTAT GCCGCCGGGA ACTGCCGTCC GTCCTGCCCC GACTCCTCAT ATCCTrrCCTr GGTTGTCACT.TCTACCTAGA GAAGGGTGTG GGCGGGTCGC GAACC'TrCT CTTCTGTCCC TTCAGACCCA CCGCCAGGCT GGG'1rATAT7 ACCGCGGCCT GAACCCCCTC T=C1TTFGT CAGTGAGTGG GATGAAAAGT GAGGGACTGG AGGGGAAGCG ACAACCGTGG TAGA'ITAAG TAAGGC'ITrG GCCCTGGAAA GCCTCGCGGA 50 CGTGTI1CTGA CCCAAGGYI1? TAGCAGTGGA TGTGGCGTI1 TCT~rCCATrC CTTCITrTCAG Tr'frTCTGTA CTCGTTGCTT GCAATTAAGT GTAAATACTT TrGCTAGTGG ATAATGGGGG AGGCAAGGAC TGAGACCTGC GGTATGACGA TAGCTCTGGC TCTVAATAGT TTGAGGTAAA GCGAGATACT CTGAGCTIT GTCTCCCGTA AAAAGGGTGG TGAATATGAA TAAGGGCTT C'rrAGCGTTA TAAGAAflAA AGGGCATAGT TCTGTGGTGT GAAATC'ITTA AAAGATGTI'C AGTAAATAAA AATGA II1C CTCCTrCCCC TCTCAGACCT C'rrrrCrrC 55 MrCTTrTCTT TITITIGAC AAGTTCTCAC TCCTCTCACC CAGGCTGGAG TCTrTCTGAA AGAGTrC'rrC CGC'I1GTI7GT TGGCITFCAA CTG'I1GGA'IT TGAGGCGCTr AGCGCCTTCT TCGTCCGGGT GCAGCACA'rr CTTGATTGGT CTCATGCC'rr TGTGG'FrGTA AATGTGCCTG GAATCCTAGC CTrTCATGGT AAACCATATG TATATGTATC 'TITCACAA CA'ITTGAGCC CAGCTTTATA CAATTACACT CAAAAGAAAA AAAGTAACCT TCACTTGAGA GAATCTCAAT ACTGCACAAA TATTGTGCAG CTAAAGCCCT ATGTAATCAC ATAGAAGTCA 60 'rrCACCTAGG CATTAGCAAA ATCTCAGAAG GTGCCAAAGC CCCCrmT r AGTI=rGTG TAGGTACAGA ACTGCCGTCT TCAAGGAGTT TCAACTTGAA AACAAATAGC CACCCTCAAA ACATTCAAAA ACAC'ITAAAC TGCGTGCATA ATGTGTGTGA GACATGGTGT TAGGCTIGG GAGAACAGAG ACACGGAACG TGATrCCTCT TCTTCCCCAC AAGCTTATAG AGAGACTTCA TI7AAGTTGAA AGTCAACATT CCCACCTAGC 'I=GCACTTFC AAACGACATA TTCAAAAAAG CCCAAACTTC CTCTAG=FT CTTCATCTGA GTAAATGGTI' TCACAAACTG 65 AAACCTTGAA TCCTCTCTGT CTCACACACC CGATCAGTAA G'rrCTA'rGT TrCTGArrCC AAACTATGTC TTGAATCAAT CCGTTrATCT CCATCCTCAT TGCTACCACT CTGATTCCAA ACCCTI7ATCA CCTCTCACTT WO 00/62736 PCT/USOO/08020 174 GGAGTATTAA TAGYTrCC'rr GT~CTACTC ATAATTCATT ATTCCAAAAA AGTrAAGAGG GGAAAAACAT AGATCTCGTC ATI17CCCM T'TAAACCACT TTACCTrCAA GGrrCCAGGT GATCTAAGCC T-rGCCCTCT CTCATACCTA GTrAATT1AAC TACACTCTGT TCATGAATAC ATTAGGCTCA CCTACCTCAA GATCTTTG CTCAGCCTGA TTTGTTCTCT CAGCC=IIG CATATITCAT GTIATGTCT TGGCCCAAAT GTCAC'ITCCT 5 TAGAGGGGCT TTTCAGAGC CTTCAATCTT AGGCAGTTCC CCCAAACGCA GTCTTACACT TGTATCACAT TGGCCTGTFC AGTTCTAA AAAGCACATT ACCATTAAAA GAAATGCTCT TG=fGC= GTATAYT~rTC CACTTCTACA CATATGTrG CAAAGTTCAT AAAGGCAGGA TG'FrGATr CTTCACAGCG TTACCCTCAG CACCTAGAAC AGTGCCTGAC ACATAGTAAG CA 11?CATAA AGGGCTAAAA ATATTTCATG TTTAAAAAT ACTTGGGAGT CTAATTAGAC AATACTI T FCAGCTTAA TGGTAGTATI' TrAGCTrCAC TATITTAACA 10 AATGAAAAAT TI'GCAATAAA TCTACAATGC CATTACCCCC CAAAATCTT 'TCATG1TT GCATFTrTACG TArrA'T=rC CAGGCCTI'AC CTGCATGTCT GCATAATCAT AACTGACTAA TITGGAACA GCTGGTAATT ATGAGCTTr TACTGAAATT TMTCATGAG GCCAA FICTA CCCTACTGAA CTCAAATT7G AGTTAATGAT GACCTCATTT TGATTGCTGC TGTAAAAAAT AAGATTTCGG AAGAGGAATG AATTCTTGTA TTACTGTGGT AGGACTATGG GTYI1TIT= GTTFGTITGT TTGTITGAG ACGGAGTCTC ACCCTGTCAC CCAGGCTGGA 15 GTGCAGTGGT'GCGATCTCAG CTCACAGCAG CCAGGTTCAA GTGATrCTCC 'ITCCTCAGCC TCCCGAGTAG CTGAGATTAC AGGCACGTGC CACCATGCCC GGCTAA1TTTT TTGTATC'ITT AGTAGAGATG GYPTCACCAT GTTGGCCAGG CTGGTCTCGA ACTCCTGACC TCGTGATCCG CCTGCCTCAG CCTCCCAAAG TGCTGGGACT ACAGGCGTGA GCCACCGTGC CCGGCCGGGT TA'rrCATrr TCTTATTAAC ATTTTGAT GATrC'FrATG GTGTrGT FAC AGTAAAACAT PTCTAACAAT TATTCTAACA ATrArrCTTG ATGGTGTATA TGAAGAAT 20 ATI'GTCGTGT MTTrGTAAGC TGCTATGTGC AGAAGAATIT CAGTCAAATA AAGYI'GGTAA GATAGGTATG TAAGTAATAT GAAAAAAGAT AGAAGGTGAT GAGTGACTA GGTATAAATT AAGTACAATA GAAATGTTGA GGAAAGAAAA AT'rTrGTA ATAGAAATCG GAAGTACAAA CTGGGCATGG TGGTGTGCAT CTCTAATCCC AGCTCCTGA GAGGCTGGTA TGGGAGGATC AC'ITrAGCCC AGGAGCTTGA GGCTGCAGTG AGGTGTGATC ATGTCACCGC ACTCCATCCT GGGTGACAGC AAGACCGTCT CTCTfTITT 'TTTrGA GACGGAGTCT 25 CGCCTATGCT GGAGTGCAAT GGCGCGATCT TGGCTCACTG CAACCTCTGC CTCCCAG=~ CAAGTGA'rrC TCCTGCCTCA GCCTCCTGAG CAGCTGGGAT TACAGGTGTG CGCCACCATG CCCAGCTAAT TATTGTAT ITAAGTAGA GACGGGTTCT CACCATACTG GCCAGGCTGG T=TCAACTC CTGACCTCTT G317CGCCCAT CTAGGTCTCC CAAAGTGCTG GGATTACAGG TGTGAGCCAC CCCAC17GGC CCCGAGCGAG ACCCTCTCTC TAAAAAAAAA TAAATAAATA AATCATAAAC CTGTGGAT17A TTGTAGCATI' GTTTCTCATC TGTCAAAAAT 30 ATrCATGAC TATGCATAGT TTGAAAAGGC AAGTITGTCC CTGGGCATr TTCAAAATAT TrCTTTAATG TGTTTTCACA ATACTGTI1A CCTAATAAAT CTTrAAGT1T TAAAAGCAAA A TAAGCCAG TAAITIGAGT CCAATTCCAA TCTCTTATGA GTCATTGCTT AAATITCAAA AGGGYMTAT TTTT=A GGTGTTCT GAGTAATGAA TACCCTATTA CTATGATACT AGTATCTTCC TTAATTATCC TACTCATJ7GT CTCAACATTC TGACAGTTGG ATI7GAGCATA ITCGTAAGTA AAATTG1TI AACTGTATGA TGTACTITGA TGTTAAGGTC 35 CGAGTCCCCA CATACCTCGG TAGATGTGTT C'ACAGTTr TGTATTCCCT TGAAATGTAA CTGTTCTCTA TGTTACAGCC TTTATAACCT TCAGTrAC'rr GAAATGAACA AATrCATTCA AAYTCCAGCA CTFAAAAGl TTAAA1TACA TITTGGATAA ATACCAAAGT G=T'FGA TGATGTATGT ATAAACAAAT TGTAAATATT AAACGTrAGT TGTTACGAYr AGACCTATAT AAAACATGAT ATGCAGTCTA CTGAATAGCT ATCAGCCTCT AACATG=IIA GTGTCA'LTA GAAAATGCTT TCTAAAITFGC CAAAAGCTGA TTGTCTAGGT GATAACAAAT 40 'TACCA'TrTG GAGGAAGTTG ACMTCTCAT TI'CATGTCT TCATCAGTCT TACTT'GATGA GA'I1'CATI'CT TCTAGTCAGA AGAGAG'TTA GACTGCTCAG TTTACTCATA =FTGAGTTA GCTITTCTAT TTAGAGTTCA CTrrGGFrGTG GAATATTCAT TTATAAYITG AATCTACGTT GTGTAATGGG ACCTAA F= TfTCCTT GTITTGTTG GAGTCTCGTT TT1GTCACCCA GGTTGGAGTG CAGTGGCGTG ATCTI1TGCTC ACTGCAACCT CCACCTFlCCA GGTICAGGTG ATTCTCCTGC CTCAGTCTCC CAAGTAGCTG GGATTACAGG CATGCTTCAC 45 CACGCCTGGC TAATTTTTGT ATTITAGTA GAGATGGGGT 'ITCACCATGT TGGCCAGGCT GGTCTCAAAA CTCCTGAGCT CAAGTGATCC TCCTGCCTTG GCCTCCATAA GTGCTGGGAT TACAGGCGTG AGCCGCTGAG CCTGGCCCCA GAGTTTG'ITT TG=r~GT TCAAGACAAG ATCTCACTCT A'ITGCCCAGG CTGGAGAGCA GTAGTGCGAT CATAGCTCAC TGCAGCCTGA ACTCCTGGGT TCAAGCTATT CTCCTGCCTC CATCTrCTAA AGTGCTGTGA TTACAGGTCT GAGCCATGAT GCTGGCCTG TGTITGTT TGTI1TT GGGGGACAGG 50 GTCTTGCTTT GTCACCAAAA CTGGAGTGTA GTGGTGCGAA CATAGCTAGC TCACTGCAGC CTCCATCTCC CACGCTCAAG CAATCCTCTC ACCTCAGCCT TCCAAGTAGC TGAGACCGCA GGTGCGTGCT ACCATGCGTG GCTAAT1TC TAYI17ATATA TT-rATI1 GGTAGACATG AGGTCT7GTC ATG=VCCCA GGTGGTC'TF AACTCCTGGG CTCAGACAGT CCTCCCGCCT CAGCCACCCA AAGTG'ITGGG ATT1ACAGGCG TGAGCCACCA TGCGTGGCAT AATTTI1' AAGTAAA FIA TTTATC TTGAGTATAG AAGTGATI'CA TG'rTCATTGT 55 GGAAAATATG AAACATATAG AAAAACAGAA AAGA ITACAA AACATCTAAT CTGAAATGGT TAAGATTTTG ATGAGAACAG TCTCATCTCA TCCGTATA TrCCTGCCAG CCTATCCATC ATTCTrCGTA CATGTTTATC TACATTAAAA TTGGTGTTAT ATITTGGAAA CTrTrGTTT AACTACATTG TGAACATIT TCATGFTTTA AAATGTCA FT TI'AATGATGG CAGATCCTAT TCAATAGATG TACACACACC TATI'AACTG GTCCACAATT GTTGGATATG TAGGTCGFI17 CC'FTrCTCTC TTTfTT TITIGGCTA CTAC'ITAATA GMPCTCTGT 60 ATAGAATGTG GTAT=TGAA AGTGTATCAA GC=rAGA'rr GGTAGTATFC TrGCA'IMAA TAAAGGGCAG TGGCCTrTGT TGACTGACAT GACAATATTT TTATAAAATT TGTTA TTGC TIACAGAAA TITGAAAAT TATTGTAGAA ATGTTTTTAC CTCATATGAA CCACCTGACA TTGGAACAGA CTITCTLTC ACAAGTGTrA CCAAAGGTAT AATACTATTA CCTGAAAATA CATGTTATAA GGAATCTAGC CTCAGTCTTA GATGATrrAT TATTAATTAT GGCTCTCTTr TTCTAATATA TCAAATATAT TCAAAATAAA AATAAGGAGT AAGTAGATCT 65 CATGTGAGAC TATAATGGTG TTAGTGTGAT CATTAGGCAG ITAAAAACTG TTACAGGCTG GGCACGGTGG CTCATGCCTG TAATCCCAGC TCTCTGAGAG GCTGAGGTGG GCAGATCATC TGAGGTCAGG AG'rrCGAGAC WO 00/62736 PCT/US00/08020 175 CACCCATGGT CAACATGATG AAACCTCGTC TCTACTAAAA GTACAAAAAA 'ITAGCTGGAC ATGGTGGCAG GTGCCTGTAA TCCCAGCTAC YI7GGGAGACT GAGACAGGAG AATTGCYJ7GA GCCTGGGAGG CGGAGGITGC ATTGAGTCAA GATCGTGCCA TTGCACTCCA GCCTGGGCAA TAAGAGCGAT GCTCCGTCTC AAAAAAAAAA AAAAAAAAAA AAGAACTTAT A=r~CAGAT TGTGTGGTFTC CnI7ACTAAC TGAATTTAAA TTATrrGTAG 5 TCAAT=~AA ATGCTCTTGT ATITAAAGC CACTGTACTC CAGCCTGGGT GACAGAGTGA AACCCTTAAT TCAAAAAAAA AAAAAAAAAA AAGAAAAGCT GGAATATTGG CAAAATCAAG TAACTAAGAG AAAACATrAA ATTCACAGAA TACATI'ATTA CArI=AGAT ATATATGGTA TATGTTPTCT CTGAAAAGCA CAAGCATACC TITITGTI7 TAAATGGAGG GAACTAAAGA TAC'IMGGTG CCAAAATGAA ACAFAMTG TAATTAATCT CTTATTGAAA TGGG'ITTCTA AC1TAGCTr TGAATCGTAA TCTTTCAAAT 'rTCTrGTACT CATAGTCACT 10 TGATGATTCT CTATCTGAAA TAM~CTTAG AA'TrGTT1CT TGACCACCAG AAAAAGATTC AACTGTTACA TAGATGAAAA TGGATGTrGA GTGTAACAG GCCTATGGGA AACAGTAT TCTTrAGCTA CATTGTATTG TTGACTGTGT TGCTATTCTT ATAATG ITA GGTCA'1TTAA ATTGTTAGAA AGATCCAAGT ATTAAGATCT AGGGTGGCTA ACTJTTCACA GACAAAAAGC T-TGTIGTAA GGTCA TrAC TATACCCTTA AT7CAGGAAG GTTAGCTTGA ATTGGGTCAA AAGGAAACTG GTI'AGAAAAT AAGTGAGTAG TGAATAGGCG A FTCAGTGCA 15 AATrCCTrCC AGAAAATACC CTTGTAAATG ACTGTATGAA TGTGGATTCT TCAAGACAGT CAAATTATr GTGCGAAAGT AATACTITA TITITGCAT CTCTAAAACA TGAAC ITTGA GTGATTIT1 AAAAAAATTG ATGCTATTAA ATAGA'ITCAA ACCATAGAAA TGGAAAATAA NI117CTGYI17 GGGGCTI=G GGGGGATTAT GTTGTAAAAA TACCTTCT CTGTA'n=G TGC~rAATrA GGTACAATI'G TI'AAGCTAGA TGATAGCCTG TGGATGTTAC TAGTGCAAAA TCAAATTATC GTATI'GTGTT TTCTCTGTAA AGTITGTCT TGTCTTTTCT 20 AGTGA1TCT CTI'AflCCTG TTTATTAcYI' GAMTGT1Tr TACAGACTGT GAAATTATTC GATGACATGA TGTATGAA'IT AACCAGTCAA GCCAGAGGAC TGTCAAGCCA AAATTTGGAA ATCCAGACCA CTCTAAGGAA TATITTTACAA GTAAGTCAAA TGTA ITAGAA AGCAGGAGAG AGAGGGAGCT TAAAGAATGT CAAAA'Tr ATACTGATAC TGATTAGCTA TGTATrCTTA TGTAATGGCC TAATGTTGGA ATTAAA1T1'A TAGAATTAAA GACGTGAATA TAGAAACATG AArCTGAAT AATAAACTCT TATAAGAAGA GAAGTCATCA AGCTAGCTGA 25 CCCTACCTGT ATI=CAAGG ATATGTGTGG AACACCTGCC ATGTGT=G AAGYITGTGT TAGTATFCTA AATGGCTAGA CAGTrGTTCC AGTATGTA GTTCTGATAG ACTAAAGTTC TGTGAAAAGA GGAAGAGACT GTGTITTGTT1 CATTGCTGTA YTrGTAGCAC CCAGCATGCT GACTAATACC TITCAGTGC ACAAAAAATA TATTrCTAAGT GAAATITCCT TCCYTATTCA CAGACAATGG TGCAGCTCTr AGGAGCTCTC ACAGGATGTG TTCAGCATAT CTGTGCCACA CAGGAATCCA TCA'FTIGGA AAATATrCAG AGTCTCCCCT CCTCAGTCCT 30 TCATATAATT AAAAGCACAT 'ITGTGCATrG TAAGGTGAGT AAAGGTCTAA FTATATTG AATGGTATAT AATCAATGTG CATAGGGGCT GAGTAAAATA ATGITITGTAT AAGATITAC ATITAGTCT ATATTAYTGA AATAAAC1TTT TCCATAGAAT AAAGAACATG TAAGTAAATA ATTGTITGCAA AAAAAGTGGT TTTAAGGAAG TCATTAAAAG TGGCTTG GGGTTPTA GTTATCTr A'TrCCCCTC TATAAAGAAA GAAGTPTTAA GAATJTGTGT TGAGACAGAC ACAGGGATCC TGAAATAGTT ATGTCATGTT GCATTGACCA ATATTCAATT 35 ACCA'FrATGA TTAGATGTCA GAACTTCCTI' TTATAAAGGA AAGTTAATCC TTA'TrTAGTC CATCTCTACA TGCCAGAGGT AGCCTTGAGG CACAAAAGCT TGCCTAGAAT 'ITATGGGTCA CAGACAGTI TAATATTGCT ATT'TG'rGGG CGAATGAAAA TCACTAG31'A ATTAATACCT CTCTTTGCTG ATAGGATGCT AAAAATGTCA CGCACCTGGC CTAATGTT1AC CC'TTIAG T-rCTGTATTT GCAAGATCAT GGAAGTCAGA AATAATATI TATACATGCT TGCATCTCT]? GAAGCACACT ATATrrAATG GATGTTCACT AAACAATGAA TGAATATGTG 40 ATTCAGTAAA TrATGATCT CTAATAGTAT GAA FTAAAGT AAATTTGGCT CTTGAGCIr GArfrG'TrrT rTCTCTCATrr TTTATrATC CGTAATCAGA ATAGTGAATC TGTGTA1TCT GGGTGTTrAC ACCTAG ITTC AGACCTT1CTC CAGGCTC'Tr TCAAGGAGGC CTATTCTCT[ CAAAAGCAGT TAATGGAACT GCTGGACATG GTI1TGCATGG ACCCTTTAGT AGATGACAAT GATGATATI17 TGAATATGGT AATAGGTGAG TGAAGAAAAC TPTCTGCTTA GTATATGGTG ACTATAAATC ATGTATCAAT TAAAATI1GTC TCTAATGAT~r CATGTTA'TT 45 TCTTACTAAT TATGCATTAA AATTGATTTA AATCTTACCA AATAAA FTI TAATCTTGAA ATTTGGAATT TGTAAAAT ATITGGGTA CCY-FAACCTA GA'TTGCGTA TVAG F7ACT GTAA'TTrCTC CACAATGATI' AACTTATATA AC FVTATAAT CTCTGAGGTT GTCCATATFC AGAGACAATA ACTTrTCACAT TTITITAACC ATAACTGATA TTGAGATGCA GTT7ATAT CCTI'CCAGAA TACATATAAA TACGTGCATA TGTGTATGTA AATATGTCTA 'ITCTCATATA CATATTATAA TGAAATAACT CATITTACAT GTGATGCACT TTATACTAGT 50 TTATITIAT TIAYITAT TTITTGAGA CAGAGTCTCA CTGTGTAGCC CAGGCTGGAG TGCAGTGGCA CAATCTCGGC TCACTGCAAC CTCGCCTCCC GGACTCAAGC GATTCTCCTG CCTCAGCCTC ATGAGTAGCT GGGATTATAG GCGTCCGCCA CCACACCTGG CTAA'T1TG TATI=AGT AGAGACAGGG TITCACCGTG TTGGCCAGGC TGGTCTTGAA CTCCTGACCT CAGGTAATCC ACCTGCCTCA GCCTCCCAAA GTGCTGGGAT TACAGGCATG AGCCACCGTG CCCAGCCAAT ACTAGTAT TITAAAGAA TTGCTGGTCG TAACACACrrT 55 CATTGATTTT ATCACTCAT7 AATGGATT1AT GAACAAGAGT 'FrGAAAAACA ATATAAAGGC AAAGTTGCA TTFCAAAAC11 TGGTATAAAG AGAGTAAGTT GG'TI1GTGC AGTGTATCAG GCACCTGTTG CTCTGCAACA CACCACCTCA AAATCTATF ATTCACTATT TATTrATTCA TGATTCTGTG AGTCTGCAGT TTAGGGTGGG ATGTCCTGAG ACAAC'TCT CTGATCCACC TGGGGCACTA GCTCACCCAT GTGACYrCAG TGACTTCA17 CACATCTGGC TGTTGGCAGA GGCAGAAGTA C31TGAGAAAG CCATGTGCAT CATCCAGCAG GTTCACCCTA 60, TCTCAGATAC CTGATGCCAG TGGTTJCAGG G~TCTAAGA GTAGCAAAAG TGTGAGCAGG TCGCTGTGTG CTAGCACTTT TCAAGTI17CT GCTTGCC'rrA ATITATTAT TGTCCCCCGG GCCACAGCAG GTCATAGCGT TTAGCCCAGA GTCATTGTAG AAAAGTGTGG ATTCACAAAG GGCAGTCATT GTGGCCATIT TTATAAATAA TCTACCACAG ACTGAGTAAA AGCCTTGCAT GAATACCATG GATATrAATT TGAATrCTTC Clr=AGAT TTrCTrTCCT TAGCAAT~G TITTGTCATT TTGGATTAGA ATTATATCTG TAGAATATrT CAGTTFATAAT 65 AGGGTACAAC TI1ATTCCA CTGAACATCT TTAGT1TTAT TTAGGTCATC TGGTAGGTAT AAACTTCAGA AG'PrAATA'Pr CAATATAT AAAAACCATr AACAAGTGTG ACAC'rTAAAT AGiTTTAAATA ATTC'rITrGA WO 00/62736 16PCT/USOO/08020 CACAACTG'rT TCCAAG'TFGT GrrACGTAYI' TTAA1TCAAT CAAATGTrGA AATTGTrCAG TAGATAGTT~r TAATTATAGG AGAAACTCAC CCCCATGACA TITGGATGTC TTAAAAGTTC TGTI'ATC'TrT C ITTGCAGTT ATTCAT'TCTI TATrGGATAT CTGCTCTGTT ATFITCCAGTA TGGACCATGC ATI17CATGCC AATACTTGGA AGTITATAAT TAAGTAAGTT TGTITGTTAT TFI=A='T TrAGAAAATG TITTCCATAT TCCCCAATCT 5 TAATTATrCA TGATrC1TA GATTGCAITTr AAAACATIT GTGTGAATY AATGYTCACT GACACTGCTG TCTGATAATC CAGATA'FrCT ACATGTAGCT CTCAAGCCAA A'FrGGAC'rrC MTACCCTGT GGCCTCTAAA ATTAAAAAAA ATGTTCTTCC TAGTTAGCTA GTACTTCAGA AATAATGGGC CATGGGCCAG ACTAGAACTr AACCACTT CTrCTGCTAC TGTTG ITAA CCAGCTATCA AGTATCCTAT TTCTAGGA Fr AGATAAATTrG ATAACTATAA TTAAAACTGA ATATAATCTr TTCATTAGGT AC FTAAGT TGTTCACACT TAAflCCATT 10 TGTACAGTAA r1TAACT CTGAAACTGA AGCA'I=AA AGGGTCACCA GGGATAGTGC CTGTAGCATr CATCAGATTC TTAGGGGTGA GAGGAGATGT GGTTGAGATG TAAAAATGGT TAAGAATATC TAC=~ATAC ACATACATAA AACATTAAAG GTCAGTGTAT 'ITTCAGGTCT TAGGTACTI TC'ITGTACTA CCAGGACA11 AAGTTGCCAT TCAGTGGTI7A AGAGTGTTGC CTGGGAGCTG TATCACATGT GCTTAAATCC ATTCTI'GAAA TCAITACTC CTICTGAGCC CTTGGGCTAT TTJGGTrAATT TCTCTGAACG 'rrAGTrTGCT CATCTGAAAA 15 TGGAAATAAT AATAGCAACT TCTTGACAGG GTTATAGTGA GAATTGAGTT CATCACTGTG AAATGCTTAG AAATGTGCAT GACACATAGT TAATACTCAA GGAATTAGCC ACATCACTAT CATCATCACT GATTATCTTC CACTCT7ACC CTCTrCCAGT TCATTICTG CCCAGCAGAA TGATC'ITA AAAAGTAAAT CAGATCATGT TACTCTATTG CTTGAAGTCT ATCCCA'TTTG ATTAAGAATA ACAACCTAAT CCTCTGTGGA TGCTGCCTCC TTCACCAGCC TGTCTCATGC TGCTCTCCCT ACTCT7AGTT CCTCAAACAT ACCAAACTCT CCTGTCCCAG 20 AGTCT=CG TGGThT-rCC ATCTGCCTAG GATGCTCTC TCTCCTATf TGTGTACCTT GCTAACTCCT GCT-FACTGTC n7TCAGTTCT CAGCTTAAGA GTTATATC'rr CATGATAACA 'rrC'IGATA TCCTTACCCT AAGATTAAGT TAGATTGATA TCCTACCCT AAGAATAAGT TAGA'rTAGGT CTCTCTATTG TAGCACCJTrA GACTCTGTCA TITGACAAAT CACAGCCCTA AI17AATTA IT CTTAAAA'rTA TTAACATTC TCTCTCATGC TAGACCACAA GTfCATGCA GGTAAGGCGG AGATTGTGTC CAn1TG1TTTG ACCCCTTTGT CTCCAGGGCC 25 TGGTAGAATG CCTCATACAT AGTAAGAATT CAATTAATAT TI'ACACAGA GAAAAAATTA GCAACFTA FF TAAACAAATA TAACTGCTTC AGAGGTAAAC TGGGCACATC TTAGTTATAT TATGTGATAT ATGATGCrrrT T'FGATTG3Tr 'IPAAATGT TCTACAAGGT AGATATTGTT AGAGGTCCTA AGTTACTTGA TGTGTTACTT GTGGTGATrG TATTCTITC 'TTrATTCA TTFAGGCAGA GCCTTAAGCA CCAGTCCATA ATAAAAAGCC AGTrGAAACA CAAAGATATA ATTACTAGCT TGTGTGAAGA CATrrC'IrC TCCTTCCArr CTTGTTACA 30 GTTAGCTGAG CAGATGACAC AGTCAGATGC ACAGGTAAAA =~GGGCTAA TAGCATITA AACAGCAACT CTTrATT TTGGCAGTTA GTAAAT.CTCA 'TFTGAATGTC TGGGTCAGTC TATITAAGAG GAYITTAA Fr TATTTCATTT GGGTGT=TT 'TITGATCTG TGGGATTATT TATATCCCAT AAYUTACYIT CACCCAGAGC ATTGTA F7AG ATTCCTAACT GCTGTCATTFG CCTCTGGGGT CTGCCTGGCT CCCTC'1GC TT1GGTAACTG GTTGGTCACA GCATTCTTCT CAGAATCCTT TCAYTT CTGCATGAGA ACAAAAATTC flTTGTTCAT 35 ATTGTATAA GATCTGATAT AGCTGCAATC AATCTTGCAT TI1TCTTCA CCAACGCATT1 GCGACCTTTA GGGATACAAG TATGTPGTG CATGTATATG TATGTATCAG TCTITAAAT TTGATATAGT CATACAYI1G TI1TAT1T GAAAAGTrAG AGTGTFGAAT TGGTATCCCA 1TI'ATGAAAC ATTATATTCT AAAAATGT AGTACGATTA ITGGGAATTA TAACTCATTT1 TCCTGTAACA CTG'PTATACA TAGTACC'TI' TGCTTCAGA CTAGCCCTCA AT=ATTTA ACTATAGTAG TCCTAAATTA TAAGATTAAT AGTACTCAGG ACCTAACAGT 40 TATATGTCAT TTGTTLT TTTTGAG ATGGCGTCTC ACTCTGTCAC CCAAGCTGGA GTGCAGTGGT ATGACCTTGG CTCACTGCAG CCTCTGCCTC ACGGGTTCAA GGGATCG117C TGCCTTAGCC TCCTGAGTAG CTGGGATI1AT AGGCGCCTGC CACCACGCCT GGCTAA'T= T TTAGTAGAG ACGGGG'TTC GCCATGTI7GG CCAGGCTGGT CTCGAACTCC TGACCTCAGG TGGTCCACCC GCCT7GGCCT CCCAAAGTGC TGGGATTACA GGTGTGAGCC ACCGCGCCCA GCCTATATGT AATAATITA ATGGGACCAT GAATTGAATA TrTCFCCrTT 45 GAATAGCAAT GACATAGCCC CTTCTATTGT ACATCTGCAA GCTGATACAG GGAATTCCT TGTACCTGCG CTCTTCCCTG CCAGTCAGCT ATGGGGGTGA AAGTGTAGGG GTTCATCCAA GTCCTAAAAC TGGTAGCAAC TCCTAGGGCA GGGCTGATCT GGAAGGACAG ACCCTAGGGG AGGGTGGAAC I=AAAAAGA AGTTrCTGAAG GTAGTAAGAA GGAAATGAGG AGTAGTGTTA GGAAGGGGCT AACTTTC TTCTI7GCTrC TCTTCVrTAT CTCACCTGCC CCTCCCCTITG TATCC=TCT TCC'TI=CC ='~CC=r~ TTrGTCCTCAC TTCATTCGTG 50 CATCCTrTCT GATTCCTCTT ACCTTGCTAA AAGGAGAAGT 'TrGTTrGGGT ATCCTATATC AATGGCAGGA AGGTT'G'TIT CTrCTTTACC 'TrATCCTAT AGATI'CATAT TCTCAACACC AACCTCCTCC TI1TCAGYI' TCCTrCITFGC TrCTC'rrGAC ACCACAGAGT 'ITGCAGCTAG TACTTGGAGA GGAAAA FrAA ACAGAGATAC TTGGACCAAG AGTAAGATGA AGAAAGTCTA AACAACAGTA TAGTCTATAG TGGCAAGAGA GAGTATGGGG GCTGCTTFAGC CAGGGTGGCT GTACATAAAG TATATC17CA GTTrATATAA ACTGCTrATA GATGGAAATC 55 AGAAAATT1'A AATTCTCTTA ACTGTCCAAG AAAATTCTCA TIT=TCAAA YITGGGACTG ATAAATGTGA CCAGT'CTGC TTACTGTCCA 31'GCCTGAAA TGGAGC TIG AGGTGGACTG TATAAT1'CT TCAATCTTAA CTCCAAATTC TGATCAGCGA CGCCCTCTGC TGTrCACTAT TAATA'1TTAT TTACCAATCA AAGTAAAGTA TTGAAGTITT CCTGGCAGTT TTCAC'TGT GTITAGTCC AT17AGGCTG CTATAACAAA ATCCCTTAAA CTGGGTAAGG GATTATAAAT ATFAGAAATT TATCTCTCAC AGTTCTGGAA GCTGGGAAGC CCAATATCAA 60 GGCACCAGTA GATTTGGTGT CTAACGAGGG TGTGCCGTCT GCTTCAAAAA TGGCCCCTTG TTGCTGCATC CTCACTTAGT GCAAGGGGCA AGACAGCTCC CT7CAACCTC TITATAAGG GCA=TATGT CATTCATGAG GGCAGAGCCC TCATGACTTA ATCACTTCCC CAAAGGCCCC ACCTC'I1AAT AGTATCACAT TGGGTGT7AG GTGTCTGGGA GGACACCAAT CTrCAAGCCA TATCATCTCA CTrGGAAAAA AGTCAAAATA AAACCAGTAG ATTTAATTAA TATTACACTA TTTATAGAAG CATGTGATGT ATCATTCCIT GTATTAATI CCTGGGG'PrG 65 CCGTAACAAG 1TACCACAAA CTAGGTGGCT TAAAACAATA GAATnI7ATr CTCTCACATT TCTAGAGGCA GAAGTTfCACA GTGTGTCAAT AGGGCCATGT TCTCTGGAAG GCTAGGGG AGAATATATT TCATATC'IM WO 00/62736 PCT/USOO/08020 177 CTCTTAGCTT CTCGGTGTCA CTGGCAATCC TTAGCTTACT TTGGCTTTCT GTGTCTTCAC ATCATCTTTT TATAAGAACA CCAGTGATAG TGATTAAGGG CATACCTTAC TTAATATGA CCTCATCTTA ACTAATTATG TCTTCAATAA CCCTATTTCC AAATAAGGCC ACATTCTGAA GTATTGGGAG TTAGAACTTA AAGCTTTTTG GGAGGGACAC AGTTCAACCC ATAACAACCC CTAAAATCGA TATTTATTCT CAATTAAGTC TTGAAATrGG 5 TTTCAAAAAG AGAATATTCT ATrAGAGTTT TTAATGTATA GTTAACAT ATAGTTCT-TT AGCCCCCAAT TTriTTT TITTrT TTTTTTT TTTTTGAGAC GGAGTCTCGC TCTGTCGCCC AGGCCGGACT GCGGACTGCA GTGGCGCAAT CTCGGCTCAC TGCAAGCTCC GCTTCCCGGG TrCACGCCAT TCCCCTGCCT CAGCCTCCCG AGTAGCTGGG ACTACAGGCG CCTGCCACCG CGCCCGGCTA ATTTTTTTGT ATI AGTA GAGACGGGGT TTCACCTTGT TAGCCAGGAT GGTCTCGATC TCCTGACCTC ATGATCCACC CGCCTCGGCC 10 TCCCAAAGTG CTGGGATTAC AGGCGTGAGC CACCGCGCCC GGCCTGCCCC CAATrATTTA GTTTTCTAT AAACAGGGAA ATTTATTTGT GTGGCCCTTA GAACTAATT AATTTCCACT CTAATrCCTA CTTATGTTTA TATAATGCTT TTAGAAATTT GTATTATTCA GAAAATAAAC ATATACTATT GTATCTGTTG CCTACACTTA GATTATTG CCTGCTATAT TTAAATTTA TTAGTATT AATTGTTA TTAAAGAAAG AATGTGCCTG TAATCTCAGC ACTTTTGAGA GGCCAAGGCA GAAGGATTGC TTGAGCCCAG GAGTTTGAGA CCAGACTGAG 15 CAACACAGGG AGACCCCCAT CTCTACAAAA AATAAAAAAA TTCTCCAGGC CTCATGGCAC ATACCTGTAG TTCTAGTTAC TrGGGAGACT GGGGTGGGAG GATGCATTGA GCCCAGGAGA TTGAGGCTGC AGTGAGCCAT GATCAGGCCA CTGTACTCCA GCTTGGACAA CAGAGTGAGA GCTTGTCTAG ATAGATAGAT AGATAGATAA TCTAAATAGA TAATAGACAG ATTATCTAAA TAGATAATAG ACAGATTATC TAAATAGATA ATAGACAGAT TATCTAAATA GATAATAGAC AGATTATCTA AATAGATAAT AGACAGATTA TCTAAATAGA TAATAGACAG 20 ATTATCTATC TAAATAGATA ATAGATTATC TAAATAGATA ATAGATAGAT AGATTAGATA GATAGATAGA TAGATAGAGC TTGGACAACA GAGTGAGAGC CTGTCTAGAT AGATAGAAAC AAAGAAAGAA AGAAAGAATG GTGCTCATAT TTTAAAGCAT TGAAAAATGG TCTTCCTTGC TTATATTACC CACACCTTCT TTGTTGGCAT TAAGATGCAA ACTTGTTTT AAACAGTTGA GTAAATCAAA GATGGGACTG TTAAGTTATT TGTGTTAT ACCTGCTT TGAAAATGTA AAAATAAAAC TCTAGGTTTA ATTAGTAGTA TGCTATTTAG TAATGAAGTA 25 AAGCTAGAGG CTTrCGAACAA ATCTTGTGTA ATTTCCTCTT GAATGAGAGA GAAAATTrAA AGTAAGCAAA CAAATAAGTT GTGTGTCACC ACTCATTCAG TCATTTAACA AGTATTTCCA GAGTACTTAT TCTGTGCCAG GAAATGTTGT AGGTGCCCTC AACAACTTAG AGTCTAGCCT GAGACACAAG TAAGTAGGTA ATTATTATAG AATGGTATGA TCTTTGGAGG ACTGGGTATT GGCTGGCTCA TGGGAGTACA AGATAGGTAC CCAGTGATGA AGTCAGGAAA GGTTTCTTAT GGTGATATGA TGACGTCTAT GCTGATTATA AGGTCAGTGT AGAATAAACT 30 TTGTGCTTTT AAATTTGCAT AGCACTGTAT TAGAGAGTTC ATCTTCAAAA TAATCGAAAA GGCTGAGTGT GGTGACCCAT GGCTGTAATC CCAGCACTTT GGGAGGCCGA GGTGGGCAGA TTGCTTGAGC TAGGAGTTCG AGACCAGGCT GGCCAACATG GTGAAACCCC GTCTCTACTA AAAATACAAA AATTAGCCAG GAGTGATGGT GCGCACCTGT AATGCCAGCT ACTTGGGAGG CTGAGGCAGG AGGATCACTT GAACCCAGGA GGTGGAGGTT GAAGTAAGCC GAGGTCATGC CACTGCACTC CAGCCTGGGC AACAGAGTGA GACTCCATCT CAAAAAAAAA 35 AAAAATGATC AAAGAAAGGT GAATTCAT CTACCCTATT TCTGCTGAGG AAAATGGACT ATTTTCAAAT ATTTTTAATA AGGGTCAAAA TGAGGGATC GCCACCATGG AAACCCTTTG CCTCAGGGCA TCCTTGGC TGGCACTGGT TGGATGTGTA ATCAGTGATA ATCCTGAGAG ATACAGCACA AATCTAAGCA ATCATGTGGA TGATTTCACC ACTTTTCGTG GCACAGAGCT CAGCTTCCTG GTTACCACTC ATCAACCCAC TAATTTGGTC CTACCCAGCA ATGGCTCAAT GCACAACTAT TGCCCACAGC AGACTAAAAT TACTTCAGCT TTCAAATACA 40 TTAACACTGT GATATCTTGT ACTATITCA TCGTGGGAAT GGTGGGGAAT GCAACTCTGC TCAGGATCAT TTACCAGAAC AAATGTATGA GGAATGGCCC CAACGCGCTG ATAGCCAGTC TTGCCCTTGG AGACCTTATC TATGTGGTCA TTGATCTCCC TATCAATGTA TTTAAGCTGC TGGCTGGGCG CTGGCCTTTT GATCACAATG ACTTTGGCGT ATTrCTTTGC AAGCTGTTCC CCTTTTTGCA GAAGTCCTCG GTGGGGATCA CCGTCCTCAA CCTCTGCGCT CTTAGTGTTG ACAGGTACAG AGCAGTTGCC TCCTGGAGTC GTGTTCAGGG AATTGGGATT 45 CCTGGTAA CTGCCATTGA AATTGCCTCC ATCTGGATCC TGTCC'ITAT CCTGGCCATT CCTGAAGCGA TTGGCTTCGT CATGGTACCC TTTGAATATA GGGGTGGACA GCATAAAACC TGTATGCTCA ATGCCACATC AAAATTCATG GAGTTCTACC AAGATGTAAA GGACTGGTGG CTCTTCGGGT TCTATTTCTG TATGCCCTTG GTGTGCACTG CGATCTTCTA CACCCTCATG ACTGGTGAGA TGTTGAACAG AAGGAATGGC AGCTTGAGAA TTGCCCTCAG TGAACATCTT AAGCAGCGTC GAGAAGTGGC AAAAACAGTT TTCTGCTTGG TTGTAATTTT 50 TGCTCTTTGC TGGTTCCCTC TTCATTTAAG CCGTATATTG AAGAAAACTG TGTATAACGA GATGGACAAG AACCGATGTG AATTACTTAG TTTCTTACTG CTCATGGATT ACATCGGTAT TAACTTGGCA ACCATGAATT CATGTATAAA CCCCATAGCT CTGTATTTG TGAGCAAGAA ATTTAAAAAT TGTTCCAGT CATGCCTCTG CTGCTGCTGT TACCAGTCCA AAAGTCTGAT GACCTCGGTC CCCATGAACG GAACAAGCAT CCAGTGGAAG AACCACGATC AAAACAACCA CAACACAGAC CGGAGCAGCC ATAAGGACAG CATGAACTGA CCACCCTTAG 55 AAGCACTCCT-3' (FRAG. NO: 1738) (SEQ. ID NO: 3009) 5'-GCCACCATGG AAACCCTTTG CCTCAGGGCA TCCTTTGGC TGGCACTGGT TGGATGTGTA ATCAGTGATA ATCCTGAGAG ATACAGCACA AATCTAAGCA ATCATGTGGA TGATTTCACC ACTITTCGTG GCACAGAGCT CAGCTTCCTG GTTACCACTC ATCAACCCAC TAATTTGGTC CTACCCAGCA ATGGCTCAAT GCACAACTAT TGCCCACAGC AGACTAAAAT TACTTCAGCT TTCAAATACA TTAACACTGT GATATCTTGT ACTATTTTCA 60 TCGTGGGAAT GGTGGGGAAT GCAACTCTGC TCAGGATCAT TTACCAGAAC AAATGTATGA GGAATGGCCC CAACGCGCTG ATAGCCAGTC TTGCCCTTGG AGACCTTATC TATGTGGTCA TTGATCTCCC TATCAATGTA TTTAAGCTGC TGGCTGGGCG CTGGCCTTTT GATCACAATG ACTTTGGCGT ATTTCTTTGC AAGCTGTTCC CCTTTTTGCA GAAGTCCTCG GTGGGGATCA CCGTCCTCAA CCTCTGCGCT CTTAGTGTTG ACAGGTACAG AGCAGTTGCC TCCTGGAGTC GTGTTCAGGG AATTGGGATT CCTTTGGTAA CTGCCATTGA AATTGCCTCC 65 ATCTGGATCC TGTCCTTTAT CCTGGCCATT CCTGAAGCGA TTGGCTTCGT CATGGTACCC TTTGAATATA GGGGTGGACA GCATAAAACC TGTATGCTCA ATGCCACATC AAAATTCATG GAGTTCTACC AAGATGTAAA WO 00/62736 PCT/USOO/08020 178 GGACTGGTGG CTCTTCGGGT TCTATTTCTG TATGCCCTTG GTGTGCACTG CGATCTTCTA CACCCTCATG ACTGGTGAGA TGTTGAACAG AAGGAATGGC AGCTTGAGAA TTGCCCTCAG TGAACATCTT AAGCAGCGTC GAGAAGTGGC AAAAACAGTT TTCTGCTTGG TTGTAATT TGCTCTTTGC TGGTTCCCTC TTCATTTAAG CCGTATATTG AAGAAAACTG TGTATAACGA GATGGACAAG AACCGATGTG AATTACTTAG TTrCTTACTG 5 CTCATGGATT ACATCGGTAT TAACTTGGCA ACCATGAATT CATGTATAAA CCCCATAGCT CTGTATTTTG TGAGCAAGAA ATTTAAAAAT TGTTCCAGT CATGCCTCTG CTGCTGCTGT TACCAGTCCA AAAGTCTGAT GACCTCGGTC CCCATGAACG GAACAAGCAT CCAGTGGAAG AACCACGATC AAAACAACCA CAACACAGAC CGGAGCAGCC ATAAGGACAG CATGAACTGA CCACCCTTAG AAGCACTCCT-3'(FRAG.NO:_)(SEQ. ID NO: 2481) 10 5'-GATCAAAATT TTTACCTATT ATGCATTTGA TATATAAATA AGTATATAAA TGCACACACA GACACAGCAA TGATGGTGAA CAGTCTTCAT ACAATTATAT GGATGAATCT CATAAAATGC TGAGTTAAAG AAATCAGACC AAAGAACATA TACTGAAAGA TTCTCTCTAT ATACAAAGTT CAAAAATAGG TGGACCAATT CATGGTGGTG TTAGAAATCA GAAGAGAGGC TACCTTGTG GGGAGGGGAC AGTTTAATGC CCAGAAGCGG TAAATAAGGA ATCCTCTGGG GAGTGGTAAT GATCTGGATG CTGGCTACAG GATGTGTTGG TTGTAAAAAT GCATTTTT 15 ATATCTAGCT TTTTCCATGT GTATATTATA CTTCAAAGAA GTTCAGTTAA TAATTTCTCA TGTCACTGTA GAGTAGCTCA GTTAGCCCCA GCAAGCCTCT GGCTTAATCT TGTTTACCT TAAGCCATCA GTCAYTACA AGTAGGAAAA TTCACAGGGA AAGTTAGAGT ATAAAATCCA GAATGAAGGT TTACTGGGTA AGAGTCTCTC CATTTTCCAA AGCCCGTTTA TCTTGATT CCAGTTCTTA AGAAGTCTCA GCATTIGTGTC TITTCATGT ATCTTACAAG AAGACAGCAT GTGCTTCTAA CACCTGATAC ATTGTATCTA CCAGCACTTG GTAAACAGAA 20 AAGAACCACA TTTCTTGT AGGAGAAATT TGGTGCCTAT TTCCTACCAG GCACCAATAA GTGGGACCAA TAGGTGGGAT TAAAGATACA GTAGAAAGTA TTTAAAACTT GCCAGGGGGC AATAGTCTGA AAATAAGTAA ATTGGTGCTA TAGAATGGAA GTTACAGGCT TCTTTCTTTT TTCCCACAAG ATCTGCTCCT TGAGCCCCTA GAGACTTTTC TGTCTGTTAC TGTTTCTTCA TTCCTCATCT GCAGAGCCAG CCCTGAGAAG TGCAGACCAA AGCCAGGGAA GGCTCTGCAA AGATGTACAA ATGGAAGTCA CCTTAATAAC CTCTGACTGC TGCGCATAAT 25 ACATTTCACT CAAAAGAGGG GTTAAACAAT GGAACAGAAT ACAGAGGCCA GAAATAATGC TGAACACTGA CAACCATCTG ATCTGACA AAATCCACAA AAACAAGCAA TGGAGAAAGG ACTCCCTATT CCATAATGGT GCTGGGATAA CTGTCTAGCT ATATACAGAA GATTGAACCT GGGCCCCTTC CTTACATCAT ATACAAAAAA TAACTCAAGA TGGAGTAAAG ACTTAAATCT AAAACCAAAC ACTATAAAAA CCCTGGAAGA TAGCCTGGGA AATACCATTC TGGACATAGG ACCTGGCAAA GACTTCATGA CAAGACACCA AAAGCAATAG CAACAAAAAC 30 CAAATTGACT AATGAAACTA ATGAAACTCT TTAGTTGTAC AACAGATAGT TTATCTGTAC AACAAAATAA ACTATCAACA GAGTAAACAA CCTACAGAAT GGAAAAAT TTTGCAAACT ATGCATCTGA CAAAGGTCTA ATATCCAGAA TCTATAAGGA ATTAAACAA ATTTACAAGC AAAAAAATGA CCTCATTAAA AAGTGGGCAA AGGACATGAA CAGATGCTT TCAAAATAAG ACATTCACAC ATCCAACAAC CATATGAAAA GATGTTTAAC ATCACTAATC ATTAGAGGAA TACAAATCAA AAGCATAATA AGATACCATC TAATACCAGT AGGAATGACT 35 ACTATTAAAA AGTCAGACAA TAACAGATGC TGGTGAAGGT TGTGGAGAAA AGGGAATGTT TATGCACTGC TAGTGGGAAT GTAAACTAGT TCAGCCATTG TGGAAGAGAG TGTGGTGATT CCTCAAAGAA TGTAAAACCG AACTGCCTTT CAATCCAGCA ATCCCATTAT TGGATATACA CCAAAAGGAA TAGAAATrGT TTTACCGTAA AGGCGCATGC ATGCATATGT TCATTACAGC ACTATTTACG ATAGCAAAGA CATGGAATCG TCTAAATGCC CATCAGTGGT AGACTAGCTA AAAAAAAAAA AATGTGGTAC ATATACATCA CAGAATAGTA TGCAGCCATA 40 AAAATGAACA AGATCATCAT GTCCTTTGCA GCAACATGGA TGTAGTTGGA GGCCATTATC CTAAGCAAAT TAATGCAGGA ACAGAAAGCC AAATACCACA TGTrCTCATT TATAAGTGAC AGCTAAATAT TGAGTACACA TGGACACAAA GAAGGGAACA ATAGACATGG GACCTACTTG AGAATAGAGG GTGGGAGGAG GGTGAGGATC AAAAAGTACC CATAGGACAC TGTGCTTATT ACCTGGGTGA TGAAATAATT TGCACACCAA ACCCCTGTGA CACACAATTT ACCTATATAG AAAACCTGTG CATGTACCCC TGAACCTAAA AGTTAATGGT GGGGGGGTGG 45 GGTTAAGCTA CTTTGTGGTA TAAATCTGAG CATTCATATT AAAATAAAAT ATTTACCTCA TTAGAGTAAT TAACATTTAT TAAGCAAAGA GCCAAGTACC TrACACACAT GATGTTTAAT CTCACAATGA TCTTTAATCT CATAACAACC GTCCATTGTA TGTACATATG TGGAAATTGA GCCTTGGAGA GATTAAATGC ATGGGGCATG CCATTTGACT AGAAACTGGA AGCATCAGGA TTTAAACTCA GTTCTGAATG GTTTTGTAGG CTTTGTTTTT TCCACATTAT AGCATGGCCT GCCATGAAGA ACAGGTCCTT TCTGGTGTTT GTCTTGTTTG GTTTAAGTGA 50 AGCAAATATT TATTTAAATA TTCAAGATAT GCTGTTAAAT TTTTACTCAA AAATTTGAGT ACAGTATGGA TCTTCTGAAG CCAAATAACT CTTATTCAAT GCTTAGTTGA GAAATAT GGAGTAGTTC TCAATTTTA TGTAGTTCCA CTGCAAAGGT AAGTCTTATG GAAAGATTCA CTGTAATT TTTTCCTCAT TTGGACATCA GCTTTTCTT TTCCTCAGAC CCGCTGAAAG ATAAT-TTA AAATAAAAAC CTTGTTTA TATCAAGTGG GGACATTIT TCCAAATGAA AACCGTGTAT TCATTATA TGATAAAATC AATGTTATTA TTTTTAAAAT 55 TTTGATTTAA AAATCATTAA AAATAAATTT TCAGATATTA CCTGAAATTC TACCATCCAG AGATAATAGT GCTTAAAGAT TTGATATATA GACACACACA CATATATACA TATATATCAT CCTAAACTTC TTTGTATAAA TGTATATAAA GTTAATA AAAACTAGGA GATTAATGCC CTTTGAATGA AAATAAATAC AATGTGTATG CTTTAACATC TTGCCTTTAC TTTATAACAT TTATCACAGC AGTCATGAGA TAATGATTTA CATGGTCATT GTTAGTAAGC TAATAGCTAA GTGCATGAAC TCTGGAGCTA GCCTCCCTGG ATTAATCC CAGATCTGTC 60 ACTGACCAGC TGAGCAATAC TAGGTAAATT GCTCTTGTTC CTTAGTTTCT TCATCTGTAA AATAGAGATA AAAATAATAT CCACCTCATA GGATTGGTGT GAGCATTAAA TGAGCATACG TATGTAGGCC ACTTAACAAC AATGCCTTCA CATACTGAAC ACAAATATAC GAGCTGTTGT CTTATTGGGC TCATGTTT CCTACCACTA AGCCGCATGC ATGCAAGGAC CATGTTGGTT TTGTTCCACA TTGCATCCCC AACCTGGTAT ACAGTGTGCA TTCAATAGTT GTTGACTATT ATTACTAGTG GCATTTAACA AATATCTGTT AAATGAGTGA AGAAATACCC 65 ATTTACTGCA AGTGTGTCTA ATATTGATGG CATAATGGGG GAAACTCAAA CTCTGGAGTC AAACAGGTTT TAAAACCTTA TTCCCTCATC CTCAGTTATT GACGTTTT TITTGGCAGG TGTGTGTGTG GGACAACTTA TTGAACTTTT CTGAATTTCC AGCTTCGCAT ATATAAAATA GAGATAGTGA TTCATTCTTG CAATGTATGG ATTTGAGACA ATTGTGTAAG TTTATCAATA AATAGTAGCT ATTGTAT AAGTATTACA TATAATATCC AGGCCACTGC TTTGCATAAC CCAAAAGGGG CACCATTCAT GCAGAATACA ACATAAATGG TGTCCCTGGA 70 GCAGTGCAGT ATAGGAACCC TGAGGGGACC TACAGTATAC TTATAGTTC ATAGATTACA AATTATCCCT TTATCAGAGT CTCTCAAGGT TGGATGTATT TGAGGTCCAT AAGAGCAATT TAGGATTAAC AGTAGCTGCA GAAACCATCT GCAGTGATAT TCTCATA AATCCGCGGG AAAGAAGACA GCTATAAACT TGGGACCTGG WO 00/62736 PCT/USOO/08020 179 G TTAAGCAT 'ITrAAATGCC AAGTTCACCA 'I1TTCTAAAA CACAACAAAT ACCCAGTGAG AGAGGGAGAA GGGAAGTAAA TGCCTCTGAA TAAGCAAG'rr AATGTCAGTA GTrGTACTGT ATGCATATTG ATGAACAATA GAGGAACCAA TGTCCAATCA GATGAGCAGG ATATIGGCA ATAACAAGTT GCC'TrTGAGG AAAAATGArT TrrC'rrGGCAA GTrC'ITATC AGCAITrACAA AGCTAAAAGC TACGCTI1ATC ATCACT-rATA CTAGCATACC 5 CTGTI7GTGCA AATGCTGTCT GTG'ITTGCAT CTGCTATTGT TGATGCCTGG TGCATGAATC AGGACTCCAG CCCACAAGTT TTCCCAGAAC T7CTTATGG CCATCATCTT TAAGTGTCTG GTGAACAGTC ATAG'FTrGGT ACACAAAAGG GTCAACCTGG GGGATGGCTA GGGIT7GACT CAGTCGT7AC A'ITTCAATAG AGCAGGAAGG GGAAATGGTG GCCTGTAACC TCAGGGAAT7 TTGCCAGTTG GTCCACCCCA CTCTCTCTCT CCTGCTCTGA GGAAGTGGCA CAGCCTAGAA CAGCACCACA GGTGAGAGAA ATGCAAACCC TAACCAGAGA AGCAGACTCT 10 TTGCCAGTAG TAATAG'I1CA GGACCACCAC CAGC'IrAT TAAAAT=IT AATAACACTC AAGTA'ITGGC AGAAAGAAAT AATCTTGGGT TAACTATAAC TAGAATATrG ACTCTTCCTC TGTGGAAGAA TCAGCCAATC ACATT7G TT ACATCAGTTC CCCTGAAGAA GAAAAATACA CTGATGTTGC AGCAAGACAA ATITAAGCTA GATGTAAATA ACTTCCTTTA GCCTGTAATG CTAGGCTAAT TACATATTGG AACTATTTI TCAGGGAAGA A'rTGTGTAGG GTTTCAGGGA AGAATFlCTGA AGAAAATATA GAGCTGAAAT GATCTTGCAG CTCACTGAAA 15 CTGCAGGGTT TAGATCCACA CTGATACTCG 'ErCTATTATC ACTGTAATGA AGGCTGATGG AATAAGTAAA AATGTrGT ATTAGTATGT TITMACACTT ATITGCAAGG CATAAATAGG TTAGGTI=G ATCTTAATfT AATTCTAACA TGTA'TGTGC ACAAGCTGTG AGCAG T=TC AGGAGT7AGG TATCTGGCCA TGACTGATV7 TTCAGGAGTT AATCATCTGG TAGAAGGGTC ATACACAATA GGAAGATGTG TGTGACAGGT TGTGATCAIT ACTATAATCA CACAGAGAGC TGTAGAATTr TAGGCTGGCA GGGTGGCTCA CGCCTGTAAT CCCAGCACTr 20 TGGGAGGCCA AGGCAGGCGG ATCAAGAGGT CAGGAGATGG AGACCATCCT GGCTAACACG GTGAAACCCC GTCTGTACTA AAAATACAAA AAAAAAAAAA AGCCAGGCGT GGTGGTGGGC GCCTGTAGTC CCAGCTACYT GGGAGGCTGA GGCAGGAGAA TGGCGTGAAC CCGGGAGGTG GAGC'IGCAG TGAGCCGAGA TCGCATCACT GCAATCCAAC CTGGGCGACA GAGGGAGACT CAGTCTCAAA AAAAAAAAAA AAAAAAAGTC ATGTTAGATC CAGAGGGGTA GCAACTGGGG CTGGGCTGTC AGTCAACTCA GTCAACTCAG TCAACTCTGC TCCCCCACAG 25 GAGATGCCAG TGATGCA'ITT TCATGGCCAA CATTGTCAGT CAGCATCATT GAA'I1ACTCC TGATrATAGA GACACAGCTG CAAACGATTC CCCATTAAAT ATGATG'TTrC 'rrGCAATG'rT TGGAAGGTAC TCCrTITMAG TAAGGGAAAT CCCCTCT-rCT GGCTrGCTGA AAGTTI=C 'TTCCATTT AAAAATCGTG AATTCCFTT TGCAATATTG AGGTGGTTAT ATGGT17TrC TrCTCTAATC TGTTAATATG GTGATTAAT GGTTAGAAAT TTTCTAATGT AAATrCCACT CATATTGCAG AAATAAACCT AAACTGAGCA TGAGGCTATA TTATEI' 30 GCTrCTATAT TTGGTTGCTA TACAGTATTA TG'TrTAAGAT 'TrGTrCACAT ATA1TTGTGA ATGGGATFTGG ACTATITPC CTTCTTGCCG A FITIATCT GGTI1AAA TrAAGGATAT =IAGACTFA TGAAATAT GGCAAACAAT CCTTGGCAAG TAATTTFG GGGAATrGT MPGGCTATT TTGAGTATTA CCCAATATAT TI-AATrAAG TI'ATI'CTIAA TG1TMCTrA ATTAAAAAAA UTACCTACTC TAGAGATATI' C'ITATGTAC TCCAGATh GTCTATIAT ACCACTITC TTI1CCTC GATGAGTGTC ATAGATGTITC ATCTATITT 35 TI'ATCTI'CTT TGATCTTCTC TTA'rrCCTTG Th1CTATTAA C'ITCTGAAGT TTATTATITT CTIT-TCCA CTTCCTTATG GTrATrCTT TCAA3TITC TCTAACTTCT TAAG TGGGT GTTTAAT1T TAGCYrGC1T TGCTITEA GGATAAGCAT TAAAACTACA AATI=CC'IT GTrrATTCTTr TGCTGCACCC CAAA'I1GTrG ATATTTCTAT TGTCTAA=T CTATTCAATT1 AGAATAC'T' AAAGfT-CTT TGG'Tr AAAAACTAAC Yr1TAAAT GACAAATAAA AATTGTGTAT AYTrATTGTG CACAGCATAT GGCTI17GAAA TATATGTACA 40 TTGTGGAATG GCTAANTTA GCTTAT7AAT GTATGCAITrA TCTCACATAC TTATCA=ITr PIGTGGTGAG AGCTATGTGA CTIIGAACT TATGAGTTAT FTAAATATTT TrAAA'ITATr AAGCATArG GGATTrAAG TAAITTTACCT 7IMATTATT AAC'ITATAAC AAGTAGAACA GTTAACCTGT ATGATTCTAC ATCATFGAAA YTTATTGACA IMGCTTCAT AGTCTATTAT ATGGTCTACT 'JTGTTCATG TTACATCTGT AGTAGAATTG GCTAATAGTT GAGTAAAGTA CACATATGTC TATGAAATCA AGTGTAATCC AGAGAAAAAG AGAAATITAC 45 TGAATATATT GTTCTAGGTG CTATTATATG 'I-TGTCATGTr TAATCCTCAC CACAATrGTA TGAGGCAGCC ATAATTAATT CCAC'ITTACA CATGAGGAGC CTGAGGGTTA AAAAAAAAGC TAGCTCTACT ATTTGTAAAG AATGAAGCAA AGATACAAAT GAAGGCCCAC ATATCC.TATA ACTAGATATT TAAGCATIT AA'rTCAAGCT TTAAAACTGC TAAATAAAAT GTGCTCCAAT TTCTATAT7G ACAGACATAC CTTCCTAATG AGCTGGGGTI' CGAATTTAGA AATCWTTGAT GCTrCAGAGT CCACACTGAA ATGTGGAGGC ACATAGTGAG TTGGTCCCCA 50 GCCTTCAGTC CACCCACCTT CTCTI17ACTA AATCACC1T CACATACATG TATGAACACC CCAGCCTCCA AGTCCAAACC CTAAACAAAA TGGGACACCC TT1GTGCATAC ACAGAGACAC AGCCCATCCT CAGGAAAACC TGGAAAAGTC CATACAAGTT CTGGAAGCAA GCTTGGGACG GTTTCAGTAG TGTGGTCTAT AAGGGAGGCC TCAGAAGACA GGTITICTTA ATTCTGTGAA CTTCTCCCAC AGTAGAAAGG GTGCTGGAGG AGGGTCAGAG TGAGGACTTC TAAAGCATGG GTCCTGAGTA GGGGCCACTC TTGCCCAAGT CTAAGAAGGG TACTAGAATA 55 GCACACTACT ACTAGATACT AGAACCCAGA TACAAGCACA GGTC1TCTGA AATTAATAAT AATAATAACT ATPFACCATTA TFATACCAGT AGCTGTCATT TATAGTGC 'rrATrATTTG CCAGTCACTG TTCTAAATTC TrACATGTA TI1ATACAACT GCCATATAAC TGCCATATGA GGGATGTACC CTCATTGTCA CCA'TITACC GATGAGAAAA CTGGCATAAA ACGTI1AAGT AACTTGTCCA AGTTACAGAG CTTAGTGAAG CCACAATGTr GCTCAATTTG CTCTCAAACT TCAAAGGGAT GGGAAGGACA CCTAAGTCAT AGAGTCTTTA AGAATCAGAG 60 CTAGAAGGAA TCTTAGATGT TATCTAGTCA GCCTCCTCCC ATTACAGTCC AAGAGAAGAT GGCCCTGAGT TACTTGTAGC TATITIGCA TGTGAA I17GC AAGTGAATAT ACATTCTACT GAAGATAAAA GATATTAAA GATATCGCTG GATATAGGAA CAGTGGYITI AAATCTCTAG GCT17AACTT TTCTCAGAAC AAGAAATCCT TTFrGGTT AATCTATATG CACATCTGTA TTTCTCAA TTATCGGGTA GTAAAATATA AC'rITTCTrC TGTAATA'Tr TITAACTTTA ATGAGTGTTC CTCATAATAG AAAAGTITrGG AAACCATTGC TATGGGTATA 65 TAC'TTrCTAA AGGGATAGTA ATfTCTCTAG AATATTCAfl TAATGCTCCA GAAGTAA FTA GCACAATFTGT GCAAGTCTGT GCATCATCAA CTATACATT1C TGCCTG TrA CTCCAAATCC ACATGAAACT GATTATACAG TCAAAGGCGA GCCCAGTGGA GAGGCATT TGGAGACTTC CTGGTACAT11 GAGACAGGGT CGGCCAGTCT GCG FrAGGGT CTFGGTCAAA ACTGCATrC TGAAACTAAA CTCAGATTGC T~rTCTI=fAA GGGGTCAGAA CTGATT1CAAA TCTACA T17 TAAAAGCCTT AGATGTGGGG CTITCCTAT TCCCAGTCTC CGCTA'FrGGT 70 C'ITTGTGAAT CCACAGGCAA TITGGCCACA TCCTTGACTC TCTCT'FATAT TAAGAATTAA ACAGCTAAGT TCATGCAGAG GAAATATAAC AAAGGAGGGA CTITCCTACA AGATC'TGA AAAATGGAAC A T-GCATAA GTCATATITA GCCAGAACTG TTG I1TTATA TITCC ITTC TGAATACTIT GTI1ACACCTC CTCCCAGCCA ACCCCCCCCC TCCCTGACCC CAACTAGTCA GAGACCAAAG CCTTCACAAT GG'ITACACT TGAACC'1CC WO 00/62736 PCT/USOO/08020 1.80 TGGCCCCACC CTCATCATCA CGCCTGAATA A'I7ACATCA CTGACTGGTC TCCCCTGCYT CCG'TTATCT CCACTCCTAA ACCCTCTGAC ACCTTAATCT TCCCAGAATA CCATTGTGAT CCTGTTCCAC TCTrGCTCAA G'n=CCCAG AAACTAGAGT ACAAAC'TJA TAAGCTIT7AG AGTTGAAAGC CACTCTATCT CITITCATC CCCAGGTCTC TGCCAAGGCA GTATAACCTG TCCAACATCT CTAACTTFCAA TACC'ITGTC TTAGATACTA 5 GACTCTCCTC CTGG'TrCTA ATrAAACCTG ATCTAGGATC TAATMGCC TCTGAATTCT GTrGCCCTr GCCAAGTGAT CTCTrCCTCC TCTGAGCCGC AGCATCTCTG AGCTTGCACA CTITAGCATAG CCATAGCACA CACAGCC'1A GCTTGCAGTT CAGGGTGTTT ACC'FlCCCTC CCCTTCCAGA TGCTGGATCC CCAGGGATAG GAACTCTGCC CTTATGTGTC CATAGCCCCT GGTAGTATGT C'I1GCAGTCG TACA'PITrCA GCAAATGTTT AATTGGTI'AA rrGAAGACAA CTGTCCCATG CCYI'AAGCCT CTCTrTITGC TAAACATGCC TGTGTCCTI7 10 GTCA17GAAC AACTATEI1TG ATCTAYTJ7C TTCCTGACAT AGGGGTCAGT TCCGAGGATG CTGAAATCAA GAGACATAGC TrATTCTCTC AAAA FrGC'rr TCAAGAGTGA TI=GTTGTG. AATTGAGAAC TGGCTGCCTA CTITTGGACT ACCCACTTCA GCAAGAGTGT TTGAAACCAA ATCTATI'CTA AGTAArrrr TATrCCCTrrr TCTCTATGGC ATTAGACACA CAGCTCTII AAACTACCTT TCGTTATCTA TTAAACAGAC A FTCAGTAAC TCTATAGACA CTGTCTAGCT ATATGAACTL' AGACAAACTA ATATCTCTGA GCTTCAGThr CTrAAAA'IT 15 AAAATGAGGA CAATACCATC TATGGCCGGG GATTAAATGC TATGAGGAAT GTAAACCAGA TGTCAGGTAC CATCTCTCTA AAATCCAGAT AAAATGAATI' AAAAATACTG GCCGCAAACC CTCTCTAAGA G'ITCTCAAAA T'TCTCAGAGA GCTTAAT=T CATGCTCACC ATAGCACCGA TVCTTCTA AATATT=GT TI'CTACCAAA ATA'TMGTC CCAATITGC CITTrATGGC TA ITCTTCA TATCCACTTT CCCAAACTAA AGAAGCAGCC CCTTCACC11? AAACTCCTCC TTCAAAGCAA CCTAAATACA GGTCTGGGTT TGTATTCCTA GTGGGATGTT 20 ACAGAGGTI'A GTGTGATGCA GAGGAGGAGT CATGCTGTr AAATCCATAC TAGTCCCCAG AGGCCAGGCT GCTTCTGCCA CCCCTACCCC TCCCGCCACA GAGCTCT[CA GCTTCTCACA MPCTAGYI7C TTCTCTCTCT ACTTTCATTA CCTTCTCTCT TITrlT=T CTTGTCATGT GCTCACGGGA GCAGAGAAAA TTAACTCCTC TAAGTTHTCT TAACACAGAG TGCCTTAA'rr ACATATI'ACT ATTG1TTGAG TTCCTGCCAA CACTACGTCT GTAGGGTCAC ACCTGCTATA TrAGAGGCTT ATCAAAAAAA GATAGCTIC TCCTAAAAAG GGATPTGGAT 25 GCCTACTAAG ATAACTGGAT GCCAAGATAA GTTTAACCTA ACAAACYI1'A TTA FTATTAT TTATrATT ATrAGAGATA GGTAC'rrA'r CTGTCACCCA GACTGCAGTG CAGGGATGCA ATAATAGCTC ACTGCAGCCT CAAAGTCCTG AGTrCATGCA ATCCTTCTGC TTCAGCTCCC TGAGTAGCTA GGACTACAGG CATATGCTAC TCTGCCCAGC TACTITTAAA AAAATAATFA GGGATGGGGT CTTGTTGTAT TGCCCAGGCT CGTCTCAAAC 'FrCTGGTrC AAGCAATCCT CCTGCCYTT ACCTCCCTAA 'rTG~rGGAGT TACAGGCATG AGCCACAGCA 30 CTCAACCAAG AITTTAAAAAC 'ITTAAAAGA AATCACATTA C2FTACTGTrA TCATCAUTAT GGTTACTACC AGTGTI7AAAA CAAT7GGTAT TGAAAACACC ACTACCAGAT CAAGCTTCAA ACCAAGATGT CAAGTAAATA TT1ATT1GTCAG ACCTCTGAGC CCAAGCCTGC AGGTATACAC CCAGATGGCC TGAAGCAAGT GAAGAATCAC AAAAGAACTG AAAATGGCCG GTTCCTGCCT TAACTGATGA CATTCCACCA TFGTGATrG TFCCTGCCCC ACCTTGACTG AGGGATTAAC CITGTGAAAT TCCTTCCCCT GGCTCAGAAG CTCCCCGACT GAGTACCTTG 35 TGACCCCCAC CCCTGCCCAC AAGTGAAAAA CCCCCTITGA CTGTAA'TM CCACTACCCA CCCAAATCCT ATAAAACAGC CTCACCCCTA TCTCCCTTCG CTGACTCTCT T7CAGACTC AACCTGCCTG CACCTAGGTG ATTCAAAAGC TTTATTGCTC ACACAAAGCC TG ITGGTGG TCTCTTCACA CAGACCATGT GACATIGGT GCCGTAACTC AGATCGGGGA ACCTCCCTTG GGAGATCAGT CCCCTGTCAT CCTGCTC'= GCTCCATGAG AAAGATCCAC CTATGACCTC TGGTCCTCAG ACCAACCAGC CCAAGGAACA TCTCACCAAT TTAAATTGG 40 GTAAGTGGCC TCTITTTTACT CTCTTCTCCA GCCTCTCTCA CTATCCCTCA ACATCTTTCT CC'TTrCAATC TTGGCACCAC GCTTCAATCT CTCCCTTCCC 'FrAATrrCAG TrCC'=CTT MfCTGGTAG AGACAGAGGA AACGTGTTCT ATCTGTGAAC CCAAAACTCC AGCACTGGTC ATGGACTTGG AAAGACAGTC TTCCCTTGAT GTITAATCAC TGCAGGGATG CCTGCCTGAT TATTCACCCA CATI17CAGAG CTGTCTGATC ACTGCAGGGA CGCCTGCCTG GATCCTTCAC CTTAGTGGCA AGTACCACTT TGCCTGGGTG GCAAGCACCA CCTCTCCTGG 45 GGGGCAAGCA CCACCTCTCC TGGGGGGCAA GTACCCCCCA ACCC=TCTC TCCATGTCTC CACCCTCTCT TCTCTGGGCT TGCCTCC'I1C ACTATGGGCC ACCTTCCACC CTCCATI7CCT CCCI=rCTC CCTTAGCCTG TGrI'CTCAAG AACTTAAAAC CTCTI'CAACT CACGTCTGAC CTAAAACCTA AATGCCTI'AC YFTCTTCTGC AATACCGCTT GACCCCAATA CAAACTCAAC AATGGTTCCA AATAGCCTGA AAACGGCACT TFCAAYI1CT CCATCCCACA AGATCTAAAT AATTCTTGTC GTAAAATGGA CAAATGGTCT GAGGTGCCTG ACATCTGGGC 50 ATrCTTAC ACGTCGGTCC CTCCCTAGTC TCTGI17CCCA ATGCAACTCA TCCCAAATCC TCCTTCTTTC CCTCCTGCCT GTCCCCTCAG TCCCAACCCC AAGTGTCGCT GAGTCITCC AATCTTCCTT TTCTACTGAC CCATCTGACC TCTCCCCTCT TCCCCAGACT GCTCCTCCTC AGGTCGCTCC CCGCCAGGCT GAATCAGGCT CCAATTC'rrC CTCAGCGTCC GCTCCTCCAC CCTATAATCC TL1CTATCACC TCCCCTCCTC ACACCTGGTC CAGCTTACAG TTTCAY7CTG TGACTAGCCC TCCCCCACCT GCCCAACAAT TTCCTCrrAA AGAGGTGGCT 55 GGAGCTAAAG GCATAGTCAA GGT'JAATGCT CCTIf=CTT TATCCAACCT CTCCCATCTC AGYTAGTATT TAGGCTfVI1T TTCATCAAAT ATGAATACCT AGCCCACTCC ATGGCTCATT TGGCAGCAAC TCCTAGACAT TrACAGCCT TGGACCCAGA GGGGCCAGAA GGTCATCTTA '17CTCAATAT GCKTITATT ACCCAATCCA CTCCCAACAT TAGAAAAAGC TCCAAAAGTI' AGACTCCGGC CCTCAAACCC CACAACAGGA CTTAATTAAC CTTGCCTTCA AAGCGTACAA TAATAGAGTA GAGGCAGCCA AGTAGCAACA TA'ITTCTGAG TTGCAAI17CC 60 YrGCCTCCAC TGTGAGAGAA ACCCCAGCCA CATCTCCAGT ACACAAGAAC TTCAAAATGC CTAAGCCACA GTGGTCAAGC ATTCCTACAG GACCTCCTCC ATCAGGATCT TGCTTCAAGT GCCAGAAATC TGGCCACTGG' GCCAAGGAAT GCCCTCAGCC TGGGATTCCT CCTAAGCCAT GTTCCATCTG TGTGGGACCC CACTGGAAAT CGGACTGTCC AACTTGCCCA GCACCCACTC CCAGAGCCCC TGGAACTCTG GCCCAAGGCT CTCTGACTGA CTCCTTCCCA GATCTTC'TG GCTI'AGTGGC TGAAGACTGA TGCTGCCTGA TCGCCTCAGA AGCCTCCTGG 65 ACCATCACAG ATGC'I=GG TAACTC11TAC AGTGGAGGGT AAGTCCGTCC CCTTCTTAAT CAATGCAGAG GCTACCCACT CCACATITACC TLTCTCTrCAA GGTCCTGLTT CCCTTGTCTT CATAAATGTT GTGGGTAYITG ATGGCCAGGC TI7CTAAACCC CTTAAAACTC CCCAACTCTG GTGCCGATTT AAACAACATT CTITATACA CTTCTI1TTA GYI7ATCCCCA CCTGCCCAGT TCCCTrATTA GGCTGAGACA ITFI'AACCAA ATTATT1TGCT TCCCTGACTA TrCCTGGACT ACAGCCACAT CTCAITGCTG CCCTTCTTCC CAACCCAAAA GTGGCAACTC 70 CTTTGCCACT TCCTCTCATA TCCCCCTACC TT1AACCCACA GGTATGGGAC ACCTCTACTC CCTCCCTGGC AACAAATCAC ACCCTCATTA CTATCCCATT AAAACCTAAT CACCC= ACC TGGGTCAACG CCAGTATCCC ATCCCACAAC AGGC TrAAA GGGATTAAAG CCTGTTATCA CTTGCCTG'Yr ACAACATGTC CT'IFAAAGC CTGTAAACTC TCCTTACAA.T TCCCCCATT1T TACCTGTCCA AAAACTGGAC ATGCCTrACA GG'TAGTFrCA WO 00/62736 PCT/USOO/08020 181 GGATCTGTGC CTTATCAACC AAATTGTCTT GCCTATCCAC GCCATGGTGC CAAACCCATA TACTCTCCTA TCCTCAATAC CTCCCTCCAA AACCCCTCCA TAACCCTTAT TCTGTTCTGG ATCTCAAAAC ATGCTTTCTT TACTATTCAT TTGCACCCTT CATCCCAGCC TCTCTTCACT TTCACTTGGA CTGACCCTGA CACCCATCAG CCTCAGCAAC TTACCTGGGC TGTACTGCCG CAAGGCTTCA TGGACAGCCC CCATTACCTC AGTCAACCCA 5 AATTTCTTCT TCATCCATTA CCTATCCAGG CATAGTTCTT CATGAAAACA CACGTGCTCT CCCTGCTGAT CATGTCCAGC TAATCTCCCC AACCCCAGGA CTGGCAAATT GACTTTACTC ACATGCCCCA AATCAGGACA CTAAAGTACC TCTTGGTCTG GGTAGACACT T7CACTGGAT AGGTAGATGC CTCCCACA GGGCCTAAGA AGGCCACCGT GGTCATTTCT TCCCTTCTGT CAGACATAAT TCCTTGGTTT GGCCTTCCCA CCTCTATACA GTCTGATAAT GGACAAGCCT TTACTAGTCA AAGCACGCAA GCAGTCTC AGGCTCTTGG TATTCAGTGA 10 AACCTTCATA CCCCTTACCG TCCTCAATCC TTAGGAAAGG TAGAACTGAT TAATGGTCTT TTAAAAACAC ACCTCACCAA GCTCAGCCTC CAACTTAAAA AGGACTGGAC AGTACTTA CCACTTGCCA TTCTCAGAAT TCGGGCCTGT CCTCGAAATG CTACAAGGTA CAGCCCATTT AAGATTCTGT ATGGACGCTC CTTTTTATTA GGCCCCAGTC TCATTCCAGA CACCAGCCCA ACTTGAACTG TGCCCCAAAA ACTTGTCATC CCTACAATCT TCTGTCTAGT CATACTCCTA TTCACCATTC TCAACTACTT GTAAATGCCC TGCCCTTT TACAGTGCTG 15 ATTTATACTT TTCCTCCAAA CCATCATAAC TGATATCTCC TGGTTACC TCAAACCGCC ACCCTTAAGT CTCTCTTAAA GTGGATAGAA GATCTTCAGT GACAAGGTAC ACTCCAATAC TTCACCCTA ATAAAGCCCT ATTCTTTACT TTTATATTCA CTCTTATTCT TGTTCCCATT CTTATGCCAC TCTCTACCTC TCCCCAGCTA TCTCCACCAC ACTATCAATC TCACTCACTC TCTCCTAGCC ATTTCTAATC CTTCTTTAAC AAACAATTGC TGGCTTTACA ATTTCTCTTT CCTCCAAAAT CACCGAGTCC TCAATTACT CACTGCTAAA AAAGGGGACT 20 CTGCATATTT TTAAATGAAG AGTGTTGTTT TTACCTAAAT CAATCTGGCC TGGTATATGA CAACATAAAA AAAACTCAAG GATAGAGCCA AAAACCTTGC CAACCAAGCA AGTAATTATG CTGAACCCCC TTGGGCACTC TAATTAGATG TCCTGGGTTC TCCCGATTCT TAATCCTTTA ATACCTGTTT TTCTCCTTCT CTTATGCAGA CCTTGTGTCT TCCATTTAGT TTCTCAATTC ATACAAAACC GTATCCAGGC CATCACCAAT CATTCTATAC GACAAATGTT TTAAGGGAGG AGACCACCCC TCATATTGTC TTATGCCCAA TCTGCCTC CAAAGAAAGA 25 AGTAAAAATG AAAAGGCAGA AATGAAATCC ACAGGCAGAC AGCCTGATGC CACACCCTGG GCCTGGTGGT TAAGATCAAC CCCTGACCTA ATCAGTTATG TTATCTATAG ATTACAGACA TITGTATGGAA AAGCACTGTG AAAATCCCTG TCTTGTTCTG TTCCTCTAAT TACCAGTACA CGCAGCCCCT AGTCATGTAC CCCCTGCTTG CTCCCCCTGC TTGCTCAATC AGTCATGACC CTCTCACGCA GACCCCCTTA GAGTTGTAAG CCCTTAAGAG GAAAAGGAAT TGTTCACTCG GAGAGCTCGG TTTGAGAC ATGAGTCTTG CCAATGCTCC CAGCTGAATA 30 AAGCCCTTCC TTCTTTAACT CAGTGTCTGA GGGGTTTGT CTGTGTCTTG TCCTGCTACA GTCATCTA ACAACCCCAT AATATCACCC CTTACCACAA AATCTTCCTT CAGCTTAATC TCTCCCACTC TAGGTTCTCA CGCCACCCCT AATCCTGCTC GAAGCAGCCC TGAGAAACAT CGCCCGTTAT CTCTCCACAC CACCCCCAAA AATTCACT GCCCCAACAC TTTACCACTA TCGTTA TTTCTTAT TAATATAAGA AGATAGAAAT GTCAGGCCTC TGAGCCCAAG CCTGCACGTA TACATCCACA TGGCCTGAAG CAAGTGAAGA ATCACAAAAG 35 AAGTGAAAAT GGCTGGTTCC TGCCTTAACT GATGATATTC CACCATTGTG ATTTGTTCCT GCGCCACCTT GACTGAGGGA TTAACCTTGT GAAATTCCTT CCCCTGGCTC AGAAGCTCCC CCACTGAGCA CCTTGTGACC CCCACCCCTA CCCACAAGTG AAAAACCCCC TTTGACTGTA ATTTTCCACT ACCCACCCAA ATCCTATAAA ACAGCCCCAC CCCATCTCCC TTTGCTGACT CTATTTGG ACTCAGCCCA CCTGCACCCA GGTGATTCAA AAGCTTCATT GCTCACACAA AGCCTGTTTG GTGGTCTCTT CACACCGACA CGCGTGATAA TTATTATATT 40 ACTTTTAACT AAAACCCTTT CAGAGTCTCG CAGGGAAGGC TGTATATATC TCATAAAATG TTGGGGCCCA CTGGATCAGA CAAGGCCACA AAGGCCAAAG GGAAGTAAAG ATCTCATTAT TTCTCCTAAT AATTTCCCTG TCCTTTGTCA TAAATGGTGG GTAGGCTGTT ATGGTGATGG CAGATTTTCT TT1CCATAAAA TGTCCATAAT AGGACATTG AACAGAAGGG AAAAATCAAA TTGCTGAAGT TGAAAGAGGG CAATGCAAAG AACTTTGGAG AAAGAACTGT ACAGAGAAGT CAACTGGCAG ATGGGAGGAA GTTTAAGGGG AAAAATATAG ATGTCTAAAG 45 AATACATTTA TTCATTCC ACAGTGCAAT TTGGACAAGA AGCCTCTTTC TTGCTTC'T CTATTCTCAT TAAATCATTA GAGCTCAAGC AATCCTTCTG CCTCAGCTTC CCGACTAGCT AGGACTACAG GTATGTGCTA CTATGCCCAG CTAATTIT AAAAATTAGA TTrAA'TTTG GTGAACTATT TCTGTAGGAA ACTACAATAA TACAGCCCAG GCACATTGAT CTTGGGTGAA CAAATCAGAA GGAATGAATA ATTCTGTGTT CCTGGGACTC TGACAATT'C ATGAACTTGG TACTCTGAGT AAAGCATAGG AGGAGTTATT TCATAAAATG TGGAGCACAA 50 TCATGTGACA AAGATAATGG GATCCCCATT TCATAAATAA ATCTGAAGTT CAGAGAGAGT AACAACTGGC CAGGGTCACA TCACGGAGAC AGAGGCAGGG TTCCCACTGA TGCCTCTGAC TCCCTGTCCC AGGCCCTTCC TCCTCCCGCA AGCAGAAGTG CAGGGGGCAG AGCTGACCCT GTGCAGTGAA AATCTGAGGG CTGAGTTCCT ATTGGAACAC AAGTGAAAGA CTTCCTGGCT TCTAATCTCA GGATAAGGAC TCAGAGCTCC ATCTGTTCCA GCCTTAGGAT AAGAACCAGA ATCTTACACC ATGAAAGCAT GAAAGGTAAG ATTTGAGTGA GGAAAAAAAA 55 AAAAAAAGTC TGTGTTTCAG'ATTCAGTTCA CAAAGCAGTT TCATACTTAA GGTACCATCA CAATAACCCT GTGGGGTAAG CAAGGCAAAT TTCATTCTTG TTATGGGC ATAGGAAGTA AGTCTCAGGG AGGTTAAGAC CAAGGTTTCT GGAGAATTTT ATATTATGAA TCTTGATTTA TGGGATTACT ATTATGTAAT TCCTAAGATC ATATAGGAAT CCTAGAGCTT GAATATAGAA CTTTATTT AAATCTATAT ACATCATAAT TACAAGGAGT AGTGTCCATT TGGGTTCCTT GGCCCTGATG TGTTAGTGGA ATAAACATT TTGTCAGGGT TGCCATGTGT 60 GTCTGTGCAC GTGTGCACTG TACACCTCCA GGGGATGTAC CCTAAACCAC ATGAATGTGA TTTGCACATC CAAGATTTAC AGTGTACTAT AGGGAGAATC TTTTGCAACA GCTTTTGCTA TAATACAGAA TCTGAGATGT CTTGAGAAA GAAAAGTGTA ATCATTACCA AAAAATTATT CTCATAATGT GTGCAAATTT GTATGAAATC TATATTGGCC ATGGGACAAG GAGGTATTTC CAGCTAGCTT CTGAAAGGGC TCTATTCTCT CATAAGAATT CAGCTGTTGA CATTAGGTGA TATCTGCCCA GGTCATCAGA TGCCATAGAG AAAGAGGGTT TGCTGAAACT 65 TATATCAGCA GTGCACTGTA TGCTCTTCT GATATTTG AACATrCATT TATTGAGTGT CAAGTAATGC ACTAGATACT CCAGGGATCT GACACAAACT CTGCCCTGAA GGAGCATGTA ATCTCACTGG GGAGAAAACA AAACATATGA TAATTTCAAA ATAACAAACT AGGCAAACTA GTTAACACTT AAAAAGCAGG CTTATTCAA ATGCAAAATT GCATGTTACA GGGTAACCTT TCAGTAAGAA GCCAGGAAGA GGAGCTCATC ATGGGTTGGA TTAGTAAAGG ACTAGTTATA AAAGAAGTGG TGGGGTTGAG GGAGGCCTGA GATGAAATTT AAAGAATATG 70 TAGAATCTAG GTAAGTGGAT AAAAGGTCTG GGGGCAGGGG AAAGGAGAGC ATTTCATTGT GAATCAAGGA ATTCTCCAC CTGTTAAC TCTTCCATAT GACATCAAAG AGATGTCACT TGCAGCTAGC ATTTCAGTGA TGTTTTCTTA CTAATAATAT CGTGATAAAA GAAACATTGA CTATAAGAAA TAGGAATGGG TCTCATAAAA GGAAACAGCA AAACCCCCAA ACTAAAAAAC AGCGCAGGCT ATTTCTCTCT TCTCTCCTTT TGCTTGGCAC WO 00/62736 12PCT/US00/08020 TCATGAGATG CTAGGTGTGG AAGTCAGCCA ACTGAAAAAG AGAGGTGGCT GAAGAAGGTG GGGAGGCTGA AGCCAGTTAA ATAGGATGGT CCAATTCACA GACGGCGAGG CTACAGTGCA AATAGGACTC 'ITCAACTrTG AGCAGGACCC CA FrACTTCA CTGGAGTTAG AAAGAAAGGA GAGCGTAGAC TV=GAACT TrCTATAAGA GTGTACCTCC ACAGTATACA GAAGACGACG TGAAA'ITTGA TCTGCAAGAA AACTGAGTCC ATATTFCACAT 5 ATGTATCAAA ITTGCACTTC ATAGAAGT GTCTGTCATC AAGTACAGCA CTGAATTGAA ACTGAAAACA AGAGTCAAGA AAGAGCAAAG TCAGCCATCT TrATATTCCA CATGAATCCT TTCCC=mAT GGTCTTAT GTTTCTCCTC AGAAAAGACA AAAAGCTGAG CTGTATAAAC ACCTGTGGGC TGGGGG'ITGA GGGATAAATG AGGGGCGAAA TGGAAGCTGA AGGAACTGTT GGTCAGGTAG AAATCTFCCC AGATGCACTG AAGGAAACAC ACT'TCATGTI' TGACGTAGGA GGTGCCACCA CACAAAACGT YFCATGGAAG GA'TrAAAGG ATCTCATGAT 10 T=AGTATT CCAAGAATTT TCTCACCA AGGGCGATF AATATGGGTC ATJ7CATACTG AAAGAAAAAC AAAAGATAAT AAGAGTTTAA AAATTGCAAA ACTTGGAGTG rrAGTAGTAA AGGTAAATAT TCATTAGAGA TGAGAAGAGG AGCAAGGAAA TGCTI1?CAGC TGGAAATCTC AGACAAGAGG CCAGGC'ITTA GGAACCTCTG AAGATGAACA AATGTAAGCA AACCCTAGTA GCAGCACT7C TCAGAITIC ATGTGCTTAC CACTCAGAGA TGGTGTTAAA ATGCAGACTC TGATTCAGTA GGTCTGAGTG GAGCCTGAGA TTCTGCACCC CTAACAAGCT 15 CTTTAGTGAT GCTTATGCCA CTGGCGCACA GACCCCACTr GGAGAAATT TTGTGGTGCA TACGGTC'TTr GTCTCCAGAT CTAATGAGTC TGAAGGACAG TGTAGATTGA 'PrITrrAAAT TTATGTT-AT ThI'AA=1AA TrTAATrAA FFrATITAT[ TMAT1T TGAGATGGAG TCTCACTCTG TTGCCCAGTC CGGAGTGCAG TGGCACGGAG GCAGCTCATG CAACCACGGC CTCCTGGGTT CAAGCGATTC TTCCGCCTCA ACTTCCTGAG TAGCTGGGAA TACAGGCACG TGCCAGCACA CCCAGCTAAT 'rrrGTATTr TTAGTAGAGA TGGGGTTTCA 20 CCACATTGGC CAAGCTAATC TCAAACTCCT GACCTCATGA TCCACCTGCC ACGGCCTCCG AAAGTGCTGG GATTACAGGC GTGAGCCACC GAGCCCAGCT GTAGATTGAT ITrGAGCAGT GGAAAGTCAA GGAATTAGAA GGCATGCT'A AATGGAAAGT GAAATrFGGAG AAAAMAAA CTCATGAAAT AGTGGTGGT-F ATAAACTCGT GATAAAYJ7AT ATCCTGGGAT ATAATI7TAAT GAGATGGTAA CACATrAGT TTAAAGAAAT AAGTGACACT TTVTT'GTGT GACACAACTG TC TATrCTT GGAAAGGACA AGGAGAGAAT GAAATATGGT ATGTCTTCAC 25 AGCACC'TrC AAAGGGAGAA CCAGATTCTG AGGAGCTGGT CTCATGATGA ACTGTCAGGG TAAACCACAG TTCAGCAGCT GCAAATGTGC TTGCCAAAAT AGAGACAAAA AAATGTCT GAAAACAAAA '1TCACATAT GCCCTCCTCT GAGGTTGGCA TCATATCTTC CTGTGTATCT TGGGTGTAGC TTCTATCCTG CCAGAATTTA GACAGTAGAA ACCAAATGAG GTGATAAACA GAGTCATIT GCAGAAGAGT CAAAATAACC CAGCAAGAAA TGAAACCACA AATGCCCAAG GAGTCATTCA TTCACCATTC AAAAGCTAAT AGAAATGAAC ACAAACTACT 30 ATGAAAAYI'C ACCCAAGAAC TTAAAAAAAA AAAAAAAGGC TCATGGTGTI' TAGTGTGATA GTArrCATTr TACC'ITTGAC TrG'rCTAAA AACACACCAT AC'ITCTACCC CACCCT1'CCT CAGTGCCGTC ACACAATGGT TTCAGTGTGA AAAAAAAAAC CACGTrACTG GAAAAGGAGG GTGCCTGGGA CTTGCCACTC TAAGCTGGTA GTCAAGGGTC TTGAGTTCTA AAAGCATACG CG3TAAGAGC ATGATTCCTG GATCCAAATG AGTATGGATC TCAGCATTGC CATFTATTGT GACCTCAGGC TATITAM1 CTCTGTGCCT GTCTTTAT CAGTAATGAA 35 GATGTI'CATA GACC = CTC CCACAGACTT AAAGGCATAT TTCATGA'TT AAGACATGTA AACCA11CAT AACAGTATAC AACATGGAAT TAATATI'rGA TAAAGGTIA TGATTATTGT AACTAACTCT GTCAC117GCT CAAGGCCTAT AGAAAACTTA CTTAATTAGT TCAACTACAA AAAGAGTTTG AATGTGATAT CCACCAAGAT CATATTCAGA CCTAGAATTC TGTGATTCTT ATGAAT-FAAT ACAGCCTrGG TCAATAAATG AGAGCTGGGC AAATAATTCT TCTITGCTAG GCCITCTAG ACCATCTGGT GAAGCATT1CA AGACTT1ATGT TA'I1GGGGCC 40 AGCCTCCTT TCCAACTTCA ACTCCACAAC TCCTCAATAA GCCATGGGCT CAAGAAAGTIT CTGCTCAGTG GCCCCTGAAA AATGCTTTCA TAGTCTCACT ACCATACCAC TGCTTACACA A'ITCCTTCC TACAGACTGC CTTCCT'ITCC TGCTTTCTC CATATACCTA AATCCTATCT ATTCTrCATA AGCAACCTTC 3TI'ATAACAT TTTCTATAAC CACCAAGCCA AATGACCTIT TCCTTC'ITAA ATATAGCACC CATTGGCCAT TACCATGCTC TGCCTTGTAT YITCTGATT T=7TCMTC TATATTCCTG TCTrAACTCC CCAGCTAGGT AATAATITC 45 CTGAAATCAG GGACCAGGCT GACTCCTCTT GCTGTCTCAA GAAAGCTTAG CAGTCCAA CACAAAAATG TTCAATAAAC AACTATTAAT TGACTGATTA TAAAAAATCA GTGAACCATT AAACTTAATA TAGCAATh17G CYI'AGCATGG TAAT7AGCTT ITTGCTAATA TrC'rrCCAGC CAGTCTCrCC TCCTGTGCCT CAAGGACATC TTAAAAAAAA AAAATCTAGT TGATCTGCTI' CCATCTAGTG GCAATTAAAA CAGGTGGTI'C CGGTAGCCAG AAAACAGCTC TGGGTAGATT GTGCCAGAAA ATACITCAC TCAGTAGGTG CGAGT~GAA AGAAATCTTC 50 ACATCTGTGG G TTCCTGCC ACAGACATAG GGAGACCAGC CCAGAGAAAG AAGCCT1'TCC TCACTAGACT CCA'ITTGCAC TAGTAAAGAG AAGACAGAGT AA ITAAAAAG AATAAAAAGA ACCTCCACTG ATCGTACATC CTCATCCAGT TACCCCTGCC CCACTTCTCC TTCACAGCCA AACATITAA AAGAGATGAC TGCTTGTTCT GTCTCTACTT TCTCATCCTC AGTAATGCTC AATGCTTGGC CGTCTGACCT CTGTCTrGAT GTCTGCACTG CAAATAGTCT CCCCACTGAC ACCCTTGTfG CATCCAGGGG ATACT'FACTG GTTCTCTTGG CAATG=rGA 55 AACCGTTCCC C'IfrCTfrGT 'rrCCTrGGCA TTCATTACCC CACACTCTT CTCCTCTTCC TrCTCCCTGC CTGGCAACAT C=hrCA'Tr CTC'TrCCCT TAGGTGACTT ATIAGATAAT GATGTTrCCTC TGGCTCCCAT ACTCTCTCCC AGGTCCTC11 CCA TCTTAA AGCACTCACA CCCTCCCTGG ATGATAGTAC CCACTCCTGA GATGGCAGTr ACCTCCTGAA ATGTGAGGGA CCCAAATCCA =TCTCCTGC CATAGCCTCT GTGC'ITGGA TAGGTCCAAT GAGCCACAGT GAATGATGTG CATACACCCA AAGCTCAGTA CAAAACTGAA CCCATGATCT 60 TTACCTCCAA AACCTCTCAT TCTrTATGT TCCCTTCTCA GAAGTAAACA GGACTACCAT CCGCCAGTrr CCAGGTGAGA AAGATGATAA TGATTCTT CTCTCTCACT =IIAGCCAAT TAACAGACAC ATrCAGTrTAA TATCACCTCC TCTITA'ITCA TGAACCCATT C'IACTACTA GTTCCCTAGA CAGGCGCCAT CGGT=TAAT CTAATAACTG CAAATGCCTC CAAAACAAGT CTCITTGAAT CCAGGCTCAC CTGTCTCCCA CACTI7GCCAT ACTGCTCTGC AGGGTGACCT TATAAGATGC CAGAGGTAAG GCTACTCACT G'rrTAAACCC CrrTAGTGAT 65 ATCCCAAAAG ACCTCAAGAT AAAGCCCATA TCACATGGCT TATACATTAG TTTATGATCT GGCTTCTGGT GCCTCAI1T TCCCCA= T'TCCTIGCA TTCTAAGCAA TGGCCCATAC TAAGTI17GTG A'TTGGTAGGA TGGTTGCCCA AACCAGCATC CAATCCC11C AGAAATCATC TCACITCATT TCTAGCA'TrT TAAAGGAAGC TCAGTT1GTCC AGCTGGGTAC TGAATATGTC ACCAAAGTCC TCCYTrCATA G TrA=L~A CTTAAACTCT CCTI7CCTAAA ATrCCAGAGC AAGTCACTAA ACCCTAGATA CTGAGAAATA 1TITCCATC '11CATTTCTG 70 CCAGGTGGGC CATCAACTTI? CACATGTCTG CATCTCCTCC CACTGTGCTA TYFCTCCAGT AGAAGAAATT TGAGCTTCAA GACCAAACTG AAAAATAC'T GCCTCCTGG GGAAGCTGTA GGTAGAATTC ATGCTCCCTA TCTTTCCCAC A'I=CTGAAG GACAATGCCT GTT1AGAGCAA TrGAATGCAA ATAGTCAATT GAATAAGCAT rrA'VCAT'r CTCAATAAGT GCTTGTTCAA TTGAATAMT CTTAAATAAT ATATTTAAGA ACAAGAAGAA WO 00/62736 PCT/USOO/08020 183* CACACCACAA TGTITAAC CCTCAGAAAA AATTCTGAGG TAATCAGAAA AATCTCCCTT TACATAAACT GCCC'TITCT AATAGGGATT AC ITGTTCGT TCA FTCATTC AITCAGCTCC ACTAGCACCA AAAAGCACAG CTCTGAAAGG AAGCTAGTAG AMIATCACC TTATCTGGTC ATTTGGATGA GGACCCCAGG TAAATAAACT ACTATGGGGT TAATGTGTCT AGCTAGAGCA GGAAGTAACT TAAGGAAGTA GAGAATGAAT CAGCAGATGT 5 GGAAACTCCT CGCCACTAAT AAAACTTACC FI'CTCTTGGA ITTCTI'GCCT GAAAATAGAA AATAGAGAAA AGGCATFAGC AAAAA'rrAGA CAATTrAAAG TI1TCAAGT AAGGGAGAAG GAAGACTCCC ACTCTCAAAA CTGTCT=FG AAGTATATTA GGTATGTT AGGTGGACCC TATCTGTGTC AAAGGAGATI1 TGAGGAACTG GCTTAATAAA CAGTGGTAGA CACTAATACA GAACAGACAT GUGATGCAG ATGCCTCCTG AGGTTCCAYr CCATTCTCCG TGCTACTCAA GAAGACAGAA 25441 TTGCTAAATT GCCTGGTGGC AAGACCCAAT 10 ATGTCCATTC AAGTGTrAT CCCTTCCCAA TCTGCCATCT CATCCTACCT GCAGATrFC'r CCCT-rGAGGG ACAGCTGCTA ATACTGTAAA ACTATGTGCC ATTACAGCTC ACAGCATCAT CTCTATGAGA ATCCACAAGA GAATCACT TTGGTCTTGT TGGTAGGAAT TGTGCAGCCT CATCTGAGTA ACTAATGTGT YTTATCTTA CAAACACAAG GAATATCACA TGGTrCTCCT TTGACTGGCT GTAAGGAAAC TCAGAGCTAG ATCTGAGACC CTCTCCTACC AAGTATATAA AAC'TrGTGA CATACA2TP TGTGCCATAA CTrCAACCTT GGTI7CCAAAT 15 GATTTGTA CCCTAAG'TI7 AAATTTGGCT TrC'mrr- TITTIGTA CTCAATAAAA CATCAAGCTC ATrATrATr GCGAAGAGCG AAACAACAAA GCTTCCACAG CGTGGAAGGG GACCCGAGTG GG'FrGCCCAA ATTGGCTTrCT TIT]CT1'ACT =IIAATI'AA 'ITATG CTATACTGAA CACATTTTGT ACTGTrrCTCA CATTC'r GAAAAAAGCA GAATATAAAT AAGTAGATAA CTTAAAAAAA ACTC1TTTGAG CAGAAAGAAT CA ITTGGGAG GCAATATATT TCAGTGGCTG TAAAGTGGCA TTCTAGAATC ATCCTACCCA GGTGAAAGCC 20 CTATTIGCC ACCTGTAGTG TAGTGTGTAT TTGAACAGCT ACTrTC'flTT CTAAACTACA A ITTCTTCAT CTGTTAAAGA GGCATAATAA TTGTATCATC CTCATTGGGT TGATAAAATA AAATA'TrTCC AAGTA=TAG TTCAGGTCCT AGCACGTAGA CAGTG TTGCA 'ITACTGTIM AATCCTAA AGTA FFAAAG ACTACTKIT GAAATCTTT CTTCTAAAAT TCAGCCTGCT GATGACCAAG TGCACTTGAG CAGGGGGAAT CAAATCTGAA T'FAATTTCAG ATrCTGG'rrA GCTTCACAT A AATArTT TTAGGGATGA TGAACCTAAC AGCAATAGAT 25 GAGTAAGAAT CTGTTCCTAC TGAGAGAGTT TCATITGAA GAAAAAGGAA CTAAGGGGGC ATGTGTrrCAG T'CATGCCC TGGTCTAACC CTGTGTGTG GTTCTGGTGG GAAATTCTTC CAACCGAGGA AAAAACCAGT TCACAAATCT GAAGACCAGT GATITMAGAA GATGTATCTG GACTGGAGTC TAATCTCTGA CTCTGGGTCC TGCTGATATG GTA'TL=GA GATIGGCCT AAAACATCAT TGCCCTGGTT TCCTI'ATITA CCAAACAGGG CCAATGGTAG TGACTAATCA GAAAATGATA ATGCCTGGTG CACAAAATGT GTCTAGATGA GCCCATGCAC 30 AAGGACACAT G'ITTCTGGAA CTGT7CCTTA TrCC'=CCT AAAAGAAAGG AGGGAAAGTC TCCATACTAA GACTACTAGO GCAGGGGACA AAGTGCTAGA GTCAGAAGAT TCATCTGAGG ACAGAAGAAT AGGGGTGAAG GCTCTAGTCA CTTCATTGGC TACCATGCTC TAAATAG~rA CCTGTGCCCT 'ITFCTAACT AYFAGAACCC AAAAAGCCTA TAAAT-rCTCT CTCTCTCTCT CTCTCTCTCT GTGTATATAT ATACATATAC ACACACACAT AGACACACAC ACACACCTAA ACACACACAT AGAGAiTTAT GACTTMAC T1TTTATCCTT GTAAATGCCA 35 TrAACTATAT TrrGTCTrAG ATrTAGCCTG GGAATGTAGC CATTA2TTCT ACCATTGCCT CCATAGGAAA AATACTCTC ATGTITTrAAA GGACCAACCT ACAACTAAAA TC'TrGGAAA GCAGAATCAT TTGTAAGTTG GTGAAAATGG AAGATGTTGT TTTATAAATG AAGACTTL 1TITITT rTrGAGACA GGGCCTCACT CTGI17GTGGA GTGCAGTGGT GCTGTCATGG C'ITACTGCAG CCTrGACCTC CTGGGTTCAA GTGATCCTCC CACCTCAGTC TCCTGGGTAG CTGGGACTAC ATGTGCATGC TACCATGCCT GACTAA=ITT 1GTAFT11 40 GTAGAGATGT GG'TrCGCCA TGTTGCCCAG GCTGGTcTrG AACTCGTGGG CTCAAGTAAT CCTCCTGCCT CAGCCTCCAA AAGTGCTGGG ATTAGAGGTG ACAGCCAAGG TGCCTGGCCC ACAGATGAAG ACTATAAT GT'ATCT7AA AGATACCCTA AGCTCCTAC CAAGCCAGTG ATCT=TGGG GCTFFCTGTr TC1TTGTTGG CATAACTGTA ACTAGCCTAA CTGCCCGrrA TCTG'I=CCT G1TIGCCCCA CACTGATrCC CACAGCAGTr YrFCAAG'TAT CGGTGAGA TCT-FGTACAG AAATGACTCC AAGGTAAAAA AITTAAAAAC AACCCCTCTA 45 ATT~TrAC CCTTGCTTAT AAAACAGCCT TAGCCAGCTA ACCCCTCACT ACATGCAAAT GAG TGATIT CTATFCTT GATTCTACAA ACACTTATTA AAAGATITA GAATTCGGAA ATAAATAGCT TCCTTATTAA GGTGAC'FrAC AGCCCCAAAG TCCT AAAAT TA'IMAGACA ATAGCCACCT TATCCCAGGG GGCAGTGTGT AATAACCCAC CCTGTTCTCT ATCCGTCAGT TCTGCCATCA TCGCCCAAGG TAGGAAGAAA GACAGGACAA CCGGGGTCAA GA'TrGAAGT CTCAATGGAA AGAATAATCA GTGGTrGGAG AAAACTGTCA TrCTrCTIT 50 GCCTTAATGC AGTACTTGAT AC'FrATACTT AGTACTGTAT AGTACTTAGT ACTGTATAAT ACTATAAGAT AGTGAGA'rC AATCAGCACA GAATCTAA TAGCAAGGGC AGAGACA TT TAACTGCTCA GTGCTCTCAG GT1TATACATA GCTAATGAAG TT1C'ITGCATA TCAACAATCC CCACCCCCCT CACACACTTT GTCTTTCTGG AT'rGGTTAGA AAACTTACCT AGCGCCCACT ATTCTCAAAT TTAAATGAAA GATAAGATCA GAGTGGCACG CAATrAGGGA CTGATAAATA ATATTTGT AA ITGCCAGT GTAAATGGAC AGGGGGCAAC CTIACATAC 55 CATATTCAGT GAACAGAATA CGTACTAACT AA TffGATGG AAGGAAAATr AAAATGACAA TCAACTGAGC CCACAGAAAG GCAACACAGA GCAGTrGGTT AGCAATTGTT TCGAGATCAT CCCTGAACTT GAAACAGGTA TATCTTTITITrTTr TTGAGACAGA GTCTCACTCT GTCACCAGGC TGGAGTGCAA TGGTGCGGTC TCAGCTCACT GCAACCTCCG CCTCCCGGGT TCAAGTGATT CTTCTGTCTC AGCCTCCCGA GTAGCTGGGA T7ACAGGTGC CCGCCACCAC GCCTGGCTAA T1TGTATT 'ITTAGTAGAG ACAGGGTrC ACCATG ITGG 60 CCAGGCTGGT CTTGAACTGC TGAGCTCATG ATCCGCCCGC CTCGGCCTCC CAAAGTGCTG GGATTACAGG CATGAGCCAC CACACCTGGC CAAAACAGGT ATATCTTAAA AGCTGCCCAA TGTCCATGAA TG'I17ACAGCC TTGAATGGTT CTTCCAGGTG AGTrGGCCA AATGTGGCAC CATACACCCA AGGCCTGCTG CAGGCTAGTG GGTT1GCTCAC ACTITAAAGC TGAGACACAC TCATGCCT7A AGGTAAAGGG AGTGATAATC TGGGCAGCAG ATG'ITAACTT CTCAAGGCAG TCCTCC'ITCT CTITCCTCT CCAGTGACGG ATGGTTGGAA AGCATATATG 65 GTGCA'TTTGG TTAGAGCTGT GGCCTTGGTG AATAGATACT TGGGAGAATA CATGGGAA11 TCTCCCAGGG 'rrAATGCAAT GCCCATGTGT TGGGAACCAG GTGACTCTTG AAGAGGTCAG GTA'ITTGGGA GCAGTGCCT7 GAAACCTFAG TGGACATTAG ACCCACTTCC TAGTGGAATT GTAGCATGA AATCCAAGGC ATGTAGGCTC TTAGAGGACA GAGATAGTGT GTCAYT-T= CAGAA'ITAAT TAAGAGCAGG CCAGGCGTGG TGGCTCACAC CTGTAATCCA AGCCCTTTGG GAGGCCAAGG CAGGCAGATC ACGAGGTCAG GAGATCGAGA CCACTCTGGC 70 TAACACAGTG AAACCCCGTG TCTACTAAAA ATACAAAAAA TTAGCTGGGC ATGGTGGCAC GCTCCTGTAG TCCCAGCTAC TTGGGAGGCT GAGGTGGGAG AATAGCTTGA ACCCAGAAGG CGGAGGTTGC AGTGAGCTGA AA'ITGCACCA CTGCACTCTA GCCTGGTGAC AGAGTGAGGC TCTGTCTCAA AAAAAAAAAA GTATTAAAGA ATTACATAAG AGCAAAGAAC CATTAGAATA TCTCACTTAG TrGTTATCAG CCTAGCAAGC TGCCTrGAAG WO 00/62736 PCT/USOO/08020 184 GTAATAGACA 'TITTTAAAAG TI'ATCAGAT GAAAAGCGAA AATCAGCCAA CCTG=hIAA TGAAGGTGTG TCCTGGGCTG A ITTACATGT CTCCAGGGAC TGATGGCTCT AGAATGTAAA GCTTGGCATC CTGCTTGTGT TGAATCTATC ACATI'AA'IT TCCTGTGGGT TTC'TIr MTCTI1TC AC'T7AAAGT TGTGTTC'TI' TCATGTGAAG TTAAACTCAC ATACCY7 TTAATCTCCT TGCCAGCCAA ATGATAAATG CCAACCCAGA 5 GAATGCAGTA ACCATGACTG CCACTGGAAT GAAGAGGGGG T-rATAATCAC CCTC=TAAT CATTGAGAAA CTTTTGTCCA ATTCTGAAAG AGAAATCAGT AAGGCACATA GCATGAGACC ACCAGCATTA TTTCCTTAGT CTATCTCATG ATATTTGACT 'T=TCCTCC TrACATCTCC CAGTAGTAGC CCATI'TGATG CCATrGACA GATGAGGAAA CTGGCATGGG AAGGCCCCTG ATGAGTCTAC AGCATAGGCA AAGACTGGAC CAGCCTTGCT AGTCTAATGC CTACAGAATC TCAATGCCCA GA'IMrGTGGT TCATAGAGTT CCTGAAAATG CACCTAAAAA 10 TGTTGGCAAG AATGGTCATC GTrGTATTTA GCTCCATGGA CTTGTTCAAT GACTGGAACT CTGAAACACA GAGAAGAGCT AAAAGCCTAA TACAAC=CA GGAAAAATAA AAGCCAATGA TCTGAACTGG ATAATrTCACC AGTCAAAGGA AATCATI'AAT GC'1rACT7 TAAAGCAGTT GTGCAAAAAT AAGCACTI'GA T=ACATG CCAAGGACCT GCACTAAT1T C=~CCAATG CAGTAGTTAC CACT7CCCTC TAC'ITCC=C ACGAATAAGT AAAAGGGCAT GTTTAGAGAT ACTCT~rGTAA GTGTAAACTA AGTI'CA IMG GGAGCCTCTA TI'GAAAATA 15 CTGGTATAAA AAAAAATCTG TCTCCTGATA CTAACA TTG AAGGAATCTA CTTTITrTACA TA'I1GGCAGA GGGTCTGATT CTATCCTTAG TTCT-fCCCAT TACTrTGATG AACCTrCA AGGTGAMFG ATCCCCACAC CCAAATATAT GATT1GAGAGA AGGCTCAAGT TCCCAGGAGC TCCAGACAGA AGGTACCTGT TGGCTTGATG AAGATGAGGA GGAAATGAAC ACTAGCTAGG CCTTAAAGGG AAATGTCTCT GATAGGCCTA ATACACAGTC CTCTGCTAAA GGCCTCCCTG CCTCTCTCTG CTCATCCACT CTACTCCCTG GCCCTGGGCA CGCAGCACAC 20 AGAGATCAGC A TrTCTGACA GCTTCTGTAG ATCCTACCAT 'TrAAAGACTT TTGTCATCCA TGCAGATAGT CTCAGGAGCA GACACAGGTA GCTATTC'ITT CACATGCTAG CTTAACATGC AT11?GCTITA GCACCTA11?G CCAGGCACTG TGTCAGGTGG AGGGTATACA AAGATGAACA AGACATGAT11 CTI7CTCATAT ACAGATAGAT TrTGGAGGCA TTAGCTTAGT GATGATT1CAG GAGTATCCAT TATTGGGGA AGTAGGTGGT CATI7AGTGAC CTTACAGG CAMIICAATG GGCTAACAGA GATGTTAGAT TGTAGTGGAA TAGAAGAATG GGTAAAAAGT 25 AAATCAGTGA GTTCAGATI1' TAGGAGTTAA GATGGCAAGA GGTGAGAACA AAAAAAGGAA ATGATTGTCA 'rTAAAGGAGG AGGAAAGACC AGCCAAAGAT TTACAGTGA GTTAAGCATA CAAAT FrArr TCTAGGCCAC ATATTCTTAG CAAAACAACA TGTAAATGTT TATGTATGTC TCCTCATA TCTGCTCATC CATCAGCTCC ATCGTTrAAGA TTTCAGYMI1 CCAGGACAAA CTTACTCACT 1TGACATATT GGACTAGGAT TTGACCAGAT TCCAGATGAT TCACAAATGG TTICT7C T CCCAATT]AAC TCAGTTCCTT CTGAGCAGAT GAAGGTACAT 30 GCAGAGGTAA AGCTGAAGCT GGCCAGGGGA TGGCTACAGT TCATGATCCC CAAATCTGGT GCTGATAGAG GCTCACACTG AATCACTTCA ATGAAAAAGA AAAAAAAAAA AAAGACAAAA CAGTA1TI'CT GAGTAGAGAC CCTCCCTTGA GCAAAGGATT TTFAGCCAAA GCTGCCTGAC TACATTACTT GTGATATTGC rTCCAGGC'rr TATTT'TCTTG AGAATGATGG TGGGTGGTGA ATGAGAGATG AAGGCAAGGA AGCATTGAAA GCTGTGGGGA GAGGAGTAGC TACTCCAGGC TGCTGCCCTA GCTAAGGTGA CCCTCCCCT11 CTGCTGGAAG TACCATGCCA 35 TATGGCCTCT GCATCAAGGG CTCTTATGGG ATATrCTCAG AGAATCTCTG CCG'ITTCATC TGTTCTGATA TCTACCCAAG CATTTTGAAA AACATCCCAA 'I1CACTGAAG CAAGTCCAAC TIFCCGTAAAT TCCAGTAGGT GGGTJGACAG Tfl7ATAATT TCAATAAGGG ATI=GATAG CAC'FrCTAAG AATTAAACTA CTTAAACTAA TGCATCAGGA GCATACTI7GT AGAAAAGT7A ACCAAAAC'IT CGTAAGTCA GATGACAT7G GTITTCTCCC ATATGGAGAT AAGGTTGGCA GTTAAAAATG AAAAAAAAAA AAAAACCTAC CTTAMPCAA ACTTGAAAAG 40 ATCAAGAGAT TGTGT=TG TT1TCAGTT GTTATlCTCC TAAAAG ITTA TGCATGAGGA AAAGTAAAAG TGA=FTAAG AATAAGCCAA ATAAAACAAC CAAGAAAGAC CTCCACTACC CTGGGAAGGA AACTGGTI'GG TATTAAGTAG GACACCACAT AAAACAGGTG TI7ATT1GAGAG GAGAAGAACC AAAATGTAAC TGAGGTI1CAA CAAGACATI'A TTTATGCAAT GGCAATGAGA AAAATAAAAA ACACAGTATA ACCATGCTGT ATTGCTATAA GTCATGTTAC ACACTGGGAG ATGGCTTCAG GGGTATIGG T=~A=I TTG=~GGGA GG TTTTCAA 45 AAAAA=IIAG 'rTAGAATAAG TCC'ITTGAGA AACATCACAG TAGGTTAAAC AAAGTTAGGT TAAATTAGGC TCCTAAG=T GACT-FCTCAG CAAACTI'CTA CTGAATGTTC TGACTGTAAG CCCAGGA'ITG CATGACAAAA CCTCTAGTCT GAAGTTACTC ACCTTGACAG GTTGGTTCTG GAGATGACCA G I=CCAAAT GGTCCACAGG TGG1T7CTTC AATCCCAGTT AAGTrGTrC CITrCAGAGCA GCTGAAGGCA CACTGTGAGC TGAAGCTGAA GTh1?CCCAAA GGGTGAGTAC AGTCCATGGT ACCCAGCTCT GGGGCCTCCA AAGGCTCACA CTGAATCACT 50 TCAATAGGGA AAGAAACAGT ATGGGGAAGA GTTAAGAGGA ACTGACGCCT GGA'ITGAAT CCTAGCCCTG CCACTTGATA ACCATGTGCC ITTAAACAAG GTTACTTGAA CCCTCCAACT TCAGTTTCTT CATCTATATA AGAGGAATAA TGAAATTrGTG TTATCTTTAT CAAATTGATA TGGAAACTAA ATGTAATI'CA ATTAGCATAA GTCAAGGACC TTAGAACAAA GCCTGACTCA TCAGAAA11C TAAGTAAACA TTAGCTAGTC TTCATATPFAT TATCTTCAGC ATI7ATCTGTA GTGAGAATCC TTAAAGCCAA ATAGGTGTAA CTGGGAATGA CCAGC'VrAGT 55 CGGGAAATAA CTATCACATC AGAGCCCCTG AGT~TACTAG AGTA'rTGGGA GCAAGATGL1 CAGAGAAAGA GTGGGTCTCC ATAATAAGCC TI7C'TFGCAA GGAGAGAATA TAAAAGTCTA GGAAGCATFT TGACCTCAAT TCTGTCTrCT ATTCTAGCTC AG'TCCAGAA TITTAACTCT TITGATITG ACAACCCTCT CCAGAAACTG TATCTMTTTC CCTG'rrCTGA TTGGTGGTAC AATAGGTAAA TTTAAGACTr GGAAATCAAA GrITTCACAT 'ITTAGACCCT GCCATGCCAT FTAGTAAACA GTACAAC'T CATGTCTTAT TCCTCATCTG TCAAATTrAA 60 GCCATTATTG CTACCTTGCT CTAGAGACTTI CAAGGAAGAA TGGACTCAAG GAATCAGAAG AATI=GTA TTTGGAAACT ATATGAGATG AGAT7AGGGA GAAACATGGG AACTAAGAGA AAATGTTATC 'TTLCATT GA'TrAAAGA GTATCTATTA TATATCAAGC ATTACTCTGG GGCTTGAAGA GCTTAGATTT CACCCTGTAG GACAAAATGG TAGGTAGAAA TTAATGGGTG GA'I1GTCATG TATGTGTGAT GTGTTrAAT TGCTITAAT TGATCAGTCT CCCTGTAGTA TGAATAATGT A'TI'GAGGGG AGCTAATrTA AAATTGTGGA ACTCATCTAA 65 TAAACTATTG CAAGAATCTA GAAGAAAGAT AATGACGGCA ATGGTAGTAG AGTI'GACAAG TGGAAGACAA ATTAGAAAAA CACTAAGTTG TAAAAATTGG TAGAATGTTA CCCTGCATAA ATGTTGGGGG AGTTAAGAGA GTCTCATACC AGGGTGCCCA TGTAAATGGT GATTCCACAT ACTGAGATAA GAAATACGAA GAGAAAAGCT GACTGGGAAC AATrGGTIT ATAGTCTIT AAACATCCCA AAGGACATCC TTAGCATATr TGAGTTCAGA GCTGGAGATA GGCTTATCAG TCCAAAGATC ACATAGAT GTGAGTCCGC AAAAGTCAGT AAGTrTGACC 70 AAAGGATACA TGTAGAUTAG AGTCAGAAGA GCAATATACA AAAGACAAAA GCTGAGAAAT TATAGTAGTT TATGGTCCTG GATAAGTGCT CATGAAGGAT CTCAGGAGAA ATGATCACAG GTAGAAAGAA TGAGAAAAGA GTGATATGAG AGAAACCAAG ACAAAGAAAA GTAAAATGTT AAAAATGAGT GAAATAGGCA TACCAATAAT TAAAAATGAG TAAAATAGGC ATACCAATAA CATAAGGGl AAAAAATAGA GTCAAAAAT GGGGTGAGGG WO 00/62736 PCT/USOO/08020 185 TAAAGTAYI'A GGAAGGAGTC ATGGCCCAGG GATCAAGTGA AATGAGTTAG ATCTATAGAT CTATITCAGT TGGTTGACAT TrAAATGTAT 'TrTGGYI=A ATrrC'rTATT GTI1'ACAAAC ATrGCTIT= TAAAAAAUTA AATTGTCCAA TTCAATTCAG GCTCACAAGC AAGTGCCTCA TATATACAGG CATPTGTGG ATCCCAAAGA TGCAATGATA AATAGGACAC 'TACTGATCT CAAGAAGITTT TCAGTACCAG AGGAGACGGA CAAGTGAACA 5 GATGACTTCA ACATAAGTGG GAGAAATGAG GAAGAAATAT GTGGAGCTAT CAGAACTAAG AAAGCTTFCCT AGAAGAAACT GTC'TIGAAC AATGTCTTAA AGATGACATG TIT1TGGCC ATGTGCAAAA TGAGAGAGAA GGCCACCAGC AAAGTCAGTG TGCTACAGAG CACATGTGTT1 AAGTGTGGAG AACTGCAAGA AGGAAAGGAA CTACTAGAAG GAAAAAGCAA GATACTI'CT GGGTAACTCA GCCTCCTAAT GATAAATGGC ATAGTTTCTT CCAGACCTTA GAGTTCTAAT TAATCTAACA AGCTCATTAG ATCGTGAGCT TCTTGAGAGC GGGAATCTAC 10 CATGCTAATT CCTTATGGTA ACCCTGACAG CTITATCCC AACACTGTGC TTCTFGTGGT ACTCAAAAAG ACTTrGTTGAG AAGTGAGTCG AAACTrCATG CTGACTT1ATG AAATCTrTAC GGAAAGGTAA CAATATTFGTG AAAGCAGAGC TTTCTGATCA AAAC'FrCCCA TrfCTCAGAG TGGCTAGTAT CATTTTGTTC CAACCAGCTr CATGATAAGC TATAATGA FT CCTGTGACTT TACCTAAGAA GAAGCAAAGA AAGGAAAGAG ACTTACCAAA CTGACACTGG GGCCCATAGT ACCCCACATC ACAGITrGCAG GTGTAA'ITAT TGATGATrTC TACACATTCT 15 CCATGGCCAC TGCATGACCA GGGCTGGCAA GAAGCTTTAA GGAGGTCAGA AAAAAAATAT TTAATGTGA TTACATr=A GTACTCAAAG TCATTTCTTT AGACATAGAT AACC'IrGT CTGAGATGAT TITAAATAATC AGGAAAGGTT TATTTGTAAA TTCATAGCAT AAAAATCATA TGCTAAAATr TrTACGTATA AAATACACTA AGCATATAGT CATAGGCA117 TAMTGCT TGGAATGAAA TTACCAATAC TAATATTCTG TAACACTTAT AGGAAACT11A GTGGCATACC 'ITGAAACTCT TGAAA FTACT TGTITIAAT GAGTGAGAAG GTTAAATGAT 20 GACCTGACCT CAATCATI'TC TGCATGCAAT TAMICTTGG CAATCCCTIT CTrATAGAA ATCAAAGATT AAAAAGTCCA AATrGCTAA AACGGTAGAG TCCAATTrAT AAGAGACCAA ATTAACTATG G'rrCAPTATr AAAACATCAC TTGGAAAATG CTGGCTG'TrT TGGAATTGTA GAAGAYTMA CAGAAATA'IT CATACACCAA AGATAGTGCA ATTT1ATAT AAAATTATAT AAGGTrTAGAC CAAGAAGGAA GCACGCAGCA CCACACTCTC TACTTCACAA TGTGAAAACT GAGGTGATGT GAGCCTAAGT TTCCAACTGG CCCCAGCTGT CAGCTTCTCC 25 TCCCCTGCCT TA'ITATCAAA GGCACTGATT GTCTAGCTCT TCCTCTGTAC YrCCTACGTA GATCTATCAT 'rrTGATGTAA CTTGA'ITTAG GGGTATAGCT TTTGTGCACA GGGACAAATC ITACACACCA AAAATTCTTA GGAGTGACAC GATGCAAGAT TATATAGAGG GCTAGATGTA TTITAGAATG AACCAGAAGC TGTTCTCATC CCCCCACC11 TCCATGGGGT AAATCTGAGT A'FrCTC'FrAA CCGTGGCCCT TCCTGAGTCT GAGGCAGCAT AGCCGTCTTG TCACTCCCTA CCTGTGTAAC AGAGGGCTGC C1TAGT~rG TGGCAGGCGT CATCGTTCCA 30 'ITTGCCTGCA TCTTTGTI*TC TCTT1GATATA GATCTCCACG CAGTCCTCCT TGTTCT7CT-F G'I1GTI1GGGC TCACCATCTC CCCAGTTCTC TGCTCTFCA GTAAGAGATT TGT7GGTTCC CACCCACGTC CATAYFrCCTC CTATCTITCCG GATTCCTATC CAGTAGTAAG AACGACTGAA AGGCAGAGTC YfCTCCAGAT ACTCAATTTC CGCCTTGTrrr TGTATGGCAA CTAAATCTGT GTAATI'GTCT CGGCAGAATC TrCTAGCCCT TrGCCAGTTC ATGGGTTP CAGAATAATG GTAAGTCCAG CAGTCGGTTC CATGATGTGC CAGGAAATCT GCAAGACATC 35 AGTGTGACCT ATGCAGACTT ACATAATGTT ACAGCTAAAA AGAACCTAGC ACTACTCCAG GCTGAGCTAG ACACTTAGAG ATGAGGAAAC AGAGCCTAAG AGTGTATGTG ACCATCTCAG GATCACAGAA TAGTTG TTG CAGMTTTGAA GTAGAACCTA GACCTrrCTGG CTTGAATATA AGATGCTIT ATCTAAGGTT CTATF~rGAAA CAAA'TAGT GGT1TCTAG G'TTATIC ITATTAATTT 'rr=CTCAAA ATrATTTCAG GTGAAATTTA ACCAACATAT TTTAGACATT CATATTC'IT =TTrrGTA GCTGTTAATG A17ACAACT AAFrACCGTG 40 TAATATCATA TAACTATACA ATTTACGTAT ACTI1AAT CCTGGAATCA TTCTTGAAG GCCAACACAT ATGTACCTAT GGGAGAAGCA TAATAAGGAC AGGAAGAACA GTGACATACT TTAAGTAAC CTCTITACA TAAAAAACAT =TAT=TAC CATAGGAAGA ACTG=TCTG GAAAAGCCCA ATATACCACT CAACTCTTAT ATATCTAACT GTATAATIT TAAAAAGAAC AATFITACAAA GCCAAATGGT ATAGGATTAT GAAATTCA11' AGATCATG'rr CTATACACAA AGAGACTCAA CTGATGATGT TTAATAAACA TATGGACCCA TCAAATATGA 45 GGGCTTrGAA GATATCTAAT TAAACACATA ATTACACAAT GACTTCATAA TAATATATGG CATTCTAAGC ATGGTATGAT CTACATGAAT CACTATI-rAA TACAGTAAAG AAACAGATAT AATrGATGGT AAAGAGCATC ATAAAATAAA CATTTTGAAC AGAGTMGA ATGAGCA'ITC CACTAGAATG CAAGTTCTAA GAGGGAAAAA ACTGTTGTGT CCACTGCTGT ATCCTT1AGTG CCTAGCATAA A'ITCACACA TI7GTAGGGAC TCAGAAAATA CCTGTTGTAT GAAAAGAGCA CTAAGTCT ATGTGACACA GTGCAGACAT GGCATAAGGA ATGTGTGAAC 50 GGGAGAG LTA GCATGTTTGC TTGGCTAGAG CTGAAAATCC AGGCTAGGGA GAAAGAAGAC ATTAGYI7AC ITAGGAAATG AAAAACCAAG 'PTCAAAGCTA 'TrGCTGGAGA GTCT1'CAAGA ATCAGATATA AAATTTGTCA CAACAATGGG AGAAGGACCA AAAAATGATA AACCCCCGTC CCTTAATAAG CTCGTA'PTGT AATTGTAGAA ATGACATI'AA TGTACACTGA ACTATGAATA AAAAATAGAA AATGAGGTGC TAAATA'TI'G GTACAGATTG TAAGTACCTT AACAGAGA'IT TCTrAATTAA CATTATTCCT TTATAA TFGA GGGATTGT GGGGTTATTG 55 GGATTTGAAC TCTACAGCAT GGGCTA'TAT AGG'ITAAAAA TAGTGTTCAG GAGTTTCTGG GGAAGAACTA AAGGTAAGAA GAAAAGAGAT GTACAGAA GGGATAGAAT TAACAGCTCT GTGAAATAAT TrTCCCTrAG ACTATGTATA ACTAGTGGAT ATTTAAGAAA AATGAATATA AGTAAAATAG ACT7AGCGAT ATATAAATAT CATAACATAC CACAACAGAG CATTGTCCAC CCCCACAACT TGAAGATGTT CCATAAGTCC CTCTGGGTGC TCTGACATT CCATGGAAAT ATCTGCAAAT GAAATACAAA ATTATAT'ITA GATGTATACT C'ITAAACCAC 60 ACATITATAG CCTITGAGGT GGTGC'I7ACA ACTTAA TAATCAGAAT AAAACACATA TGTCTACTAA CCCTGTCTGA GGTAACAGGT TTCTCAGACA TAGATGAAAA ATTACTTCAA ATTTACATCA GAACTGATGC ACAGTPGT =IGTTCTAT 'T'ATrfA CGCn7~AGTC TCAAGTTGCT AATCGGTACT GCCCTGAAT 1TICTATGG TTTGGTAATT 'ITrATACCTG CYITCTGCT GAGCTATI'AG ATAAAACTAT TTAATATIT7A CTATGTATAT ITITAAAGT ATTGTTGCTG CTTAATTAAC TATTGATGCT TATAMTAAT GTrATAGCCT 65 CACTC'ITGAT CATAATGGGT CAATGCCTCA AATACCTAAA AAAAAAAAAA ATTAGATAGC CAGACACCAG GAAAGAAAAG TATCTITT TIAATAAAA AGAAATACCT TIT~GAGCAA CTGAAATGAC AAAGTCACAA ATTTCCTGCA CACCTTAAAA TATACITAAT GTAAATGACG AG LTAATGGG TGCAGCACAC CAACATGGCA CATGTATACA TGTGTGACAA ACCTGTATGT TGTGCACATG TACCCTAGAA C ITAAAGTAT AATITTAAAA AAATF'CTATC TTrCCAAAGCA TATCACTTCT CAGGTAGACA CAGTGITI'AT TGCAAAAGAT CTGATrCAA 70 TAGTA'TrCT TCAAGAGTCT CCCCAGAGAC AAAGTCAAGA AGAGGAAATC AGCATATCTG AGAAGAAAGA TITCAGGATC ACTTTIG AGGGTCTGAG AAAATGTA GTTTCTATAT TATITAAAAC CAGAA'rTGAA ATGGGGTGAT TCCTATCC11 GCCACCTGCC TCTACAACCC CAAGAG'ITrC TATCTGAGCA TCTAAACGTC TTTTAGGCTG AAAGGCTCAC CATGGCTrG C'ITGGTCCT CTCTAGTTCT TCTGCAGCCC ATTGAGCCTC WO 00/62736 PCT/USOO/08020 186 TFGACTTAGC ACAAGGGTCT CAGGTCCflTG CCCAAAGGGA GTGTGCTGTG CTGCAGGTAG ACTGCACTGA ATGTCAACAG AAAGCCTTGC TTCTTTCAT TI7CTCTAACC CAGTCTCACA TCCTCCTCCT CCTCCCCTTT TCCCTCCCCT TCCTCCTGCA CTTCTC1TJ7C CTC'I=CCCC ACCCC'ITCC TAGACTGGCC TCTATTGCCT CCCACTGAGA CAAAAATGAA CTGCTGATCA GAAAGTAATG TGACTAGATr CTCTCTTCCT TCCCTCCT'rr 5 CTATCCTTCC TTCCATTCTC CTATGCATCT 'rrCCFrACCC TCCTCCTCCT TCACTCATrG TTGTTGCTGT TCTTrC'I7CCT C'ITTTIC CTCCTGCTCC TCTTCTTCTA CTTGTTCTTG TTCTTG3T= TGTTTGGTTC 'ITGTTCTCCT CTrCCTCCT7 CTCTCTCTCC TCCTCCTCCT TCTITrTCCAC CACCCTCCCC TATCTTTC ATAAATGCTA AACTAACTCT TGGCTACCTG TGGTAAATGG CCCTI7GGAAA TTGCAAATAC TACAAATCAA AACTGCA'IT CAGACATA17 TATGATGTIT GCAAAACTTC AGTAGAGCTA AGCAGTGGAC TTGACTCG'rr 10 TCGGTTCCTT CACCTCCGTC TrCC'FrGCT CACCACCTAG TGGACGTCCT TGTTAGTGGC AC'I1CCTGAA GTTAACCCCT GAAGAGAGCC CATGCTCTCT AGCTITCAC CGTGTAGGT7 TGGGAGCCTA CAAGTACCT~r TAATA FTCTT GGACTATAAA ATGAGATGGT MTATAAGAC TGCATGTGAA ATTAGGACCC ATATGATGAA GGACAATAAA AAGGAAGACC CACTGATGTG AGTCAATGAG TCAAATGCAA ATCAGA'IMG CATT=AGG AAAATAATAA TAACAACAAC AAAAACTCTG AAGCTCAGCG CCCCATAMT ATI'ATATTGT TTAATCTTTA 15 TAACAGCTCT CTGCTATAGA TATGAflATT ATCCCCATIC TAAAGAGTCT CAAAGAGGTI' AAGAAACAAA TTCAAAAACT AGCGAAAGAC AAGAAATAAC TAAGATCAGA GCAGAACCAT AGGAGGTAGA GACACGAAAA AGCC'CAAA AAATCAATAA ATCCAGGAGC TGCAT=TGA AAAGATTAAC AAAATAGATG GACCACTAGC TAGACTAATA AGAAAGAAGA ATCAATAGAC ACAATAAAAA ATGGTAAAGG GGATATTACC ACTGATCCCG TAGAAATACA AACTACCATC AGAGAYFACT ATAAACATCT TI'ACACAAAT AAACTAGAAA ATCTAGAAGA 20 AATGGATAAA TTCCTGGACA CATACACCCT CCCAAGACTA AACCAGGAAG AAGTCAAATC CCTGAATAGA CTAATAACAA G ITCTGAAAT TAAGGCAGCA ATrAATAGCC TACCAACTAA AAAAAGCCCA GGACCAGATG GATTCACAGC CAAATTCTAC CAGAGGTACA AAGAGGTGCT GGTACCA'ITC CTTCTGAAAC TATTCCAGAG AATAGAAAAA GAGGAACTCC TCCCTCACTC ATITATGAG GCCAGCATCA TCCTGATACT AAAACCTGGC AGAGACACAA CAAAAAAAGA AAATI1TCAGG CCAATATCCC TGATGAACAT CATITGCGAAA ATACTCAATA 25 AAATACGGCA AACTGAATCC AGCAGCACAT CAAAAAGCTT ATCAACCACA ATCAAGTT1GG CTTCATCCCT GGAATGCAAG GCTGGTTCAA CATACACAAA TCAATAAACA GAATCCAT11A CGTAAACAGA ACCAATCACA AAAACCACGT GA I1ATCTCA ATAGATGCAG AAAAGGCCTT GGATAAAATT CAACACCCCT TCATGCTAAA AACTCTCAAT AAACTAGGTA TTGATGGAAC GTATCTCAAA ATAATAAGAG CTA =ATGA CAAACCCACA GCCAATAGCA TACTGAATGG GCAAAAACTG AAAGCGTTCC C1T7AAAAAC TGGCACAAGA CAAGTATGCC 30 TCTCTCACCA CTCCTG'ITCA ACATAGTATT GGAAGTCTG GCCAGGGCAA TCAGGCAAGA GAAAGAAATA AAGTGTATI'C AAATAGAAGA GAGGAAGTCA AAT7GTGTCT GTTGCAGAT GACATGATTG TATAITTAGA AAATCCCAY7 GTCTCAGCCC AAAATCTCCT TAAACTGATC AGCAACTTCA GCAAAGTCTC AGGTTACAAA ATCAATGTGA AAAAATCACA AGAATTCCTA TACAGCAATA ATAGACAAAC AGAGAGCCAA ATCATGAGTG AACTCCCATT CACGATTGCT ACAAAGAGAA TAAAATACCT AGGAATCCAA CTTACAAGGA ATGTGAAGGA 35 CCTATTCAAG GAGAACTACA AACCACTGCI' CAAGGAAATA AGAGAGGACA CAAATGAATG GAAAAACATT CCATGCTCAT GGGTAGGAAG AATCAATATC ATGAAAATGA CCATACTGCC CAAGGTAATT TATAGAYIFCA GTGCTATCCC CATCAAGCTA CTACTGACTT TITCACAGA ATTAGAAAAA AACTACITTA AA ITTCATAT GGAACCAAAA AAGAGCTTGT ATAGCCAAGA CAATCCTAAG CAAAAAGAAC AAAGCTGGAG GCATCATGCT ACCTGACTTC AAACTATACT ACAAGGCTAT AGTAACCAAA ACAGCATGGT GCTGGTACAA AAACAGATAT 40 ATGGACCAAC GGAACAGAAC AGAGGCATCA GAAATAACAC. CACACATCTA CAACCATCTG ATC'ITTGACA AAGCTGACAA AAAGAAGCAA 'TGGGAAAGG ATTCCCCATT TAATAAATGA TGYTGGGAAA ACTGGCTAGC CATATGCAGA AAACTGAAAC TGGATCCCTI7 CC'I7ACACCT TATATAAAAA TTAACTCAAG ATGGATTAAA GACTAAATG GAAGACCTAA AACCATAAAA ATTCTAGGAG AAAACCTAGG CAATACCAT7 CAGGACGTAG GTATGGGCAA AGACTI'CATG ACTAAAACAC CAAAAGCAAC AGCAACAAAA GCCAAAAT1'G ACAAATGGGA 45 TCTAATTAAA CTAAAGAGCT TCTGCACAGT AGAAAAAAAA AAACTATCAT CAAAGTGAAC AGGAAACCTA CAGAATGGGA GAAAATITM GCAATCTA'PT CACCTGACAA AGGGCTAATA TCCAAAATCT ACAAGAAACT TAAACAAATT TACAAGAAAA AACAAACAAC ACCATCAAAA AGTGAGTGAA GGATATGAAC AGATGCTT CAAAAGAAGA AGTI1'ATGCA GTCAACAAAC ATATGAAAAA AAGCTCATCA TCACTGGTCA TTAGAGAAAT GCAAATCAAA ACCACAATGA GATGCCATCT CATGCCAGTT AGAATGGCGA 'ITATTAAAAA GTCAGGAAAC 50 AACAGATGCT GGAGAGGATG TGGAGAAATA AGAATGC'I= TTACAGTGTT GGTGGAAGTG TAAA'ITAG'rr CAATCA L1GT GGAAGACAAT GTGGCGATIT CTCAAGGATC TATAACTAGA AAAACCAITT GACCCAGCAA TCCCATTACT GGGTATATAC CCAAAGGATT ATAAATCATT CTACGATAAA GACACATGCA CAC-17ATGTT TATTGAGGCA CTAT7CACAA CAGCAAAGAG TT1GGAACCAA CCCAAATGCC CACCAATGAT AAACTGGATA AAGATGATGT GGCACATATA CATCATGGAA TACTATACAG CCATAAAAAA GGATGAGTTC ATGTCC'TTrG 55 CAGGGACATG GATGAAGCTG GAAACCGTCA TT1CTCAGCAA ACTAACACTG GAACAGAAAA CCAAACATTA CCCAT'TCTCA CTCATAAGTG GGAGTTGAAC AATGAGAACA CATOGACACA GGGAGGGGAA CATCACACAC TGGGGCATGT CAGGGGATGT GGGGCTAGGG GAGGAACAGC ATTAGGAGAA ATACCTAATG TAGATGACAG GTTGATGAAT GCAGCAAACC ACCATGGCAC ATGTATACCT ATGTAACAAA CCTGCACGTT CTGCTCATGT ATCCCAGAAA rI'AAAGTATA A'ITTAAAAAA AGTTTAAAAA AAGAAAGTI'G CCTTAGTCAC ATAACTAGTA 60 AGAGACATGG TTGGGAAT-TT GAACAGAGGC CAATCAGrC CAAATCCATG CTCTI'GATCA TJ7AAGCTGAA CTTATGGCAG GAACTGGAA GACATGGTAA AATGGGGAAA AACGTGGAGC CAGGGAGACT TGTGAAAGTG CCAGTGCTCC CACTATACCC TGAAAGAAGT ATCTAGACTT ACTITT'rCT AAGTCCTCTC CTCTAATTCT CTCAATCTCT CTCTCTC1TT CTCTAAGAGA TGGGAATGCT GCTCTGTCAC TCAGGCTAGA GTGCAGTGGT GCGATCATAG CTCA'FrGCAC TCAAGGAATC CTAGGGTCTA GTGCCCCTTC TCCCTCAGCC TCCCATGTAG 65 CTAAGACTAC AGGCACATGC CCCAACCCTC GACTAATI1 MfATTT ATITGTAG AGACAGGATC TCACTATG'IT GCTCAGGCTG TAATTCTGTC TITGAAGCTTG TCCAATCAGG CWCAGCCA CACCAATTCC CTGAGACTGC TCTCACCAAG GTCCTACACT TCACTAACAC AAACAGCCTA TTCTCCATCC TCATCTTACT TCACCAGGGA GCTCCTGGTT1 TTCCTCCTAC T7CACTGGCT A TT=CTG TATCATGTGT TGATrCTCCC TCATCTCCCC AACCTCCAAA CCCTrGGAGT ACTCCAGAGA TCACCGC'ITT GCTCI17CTGT GTCTAACCTC 70 ACTAACTTGG TGGTCCAAT7 CACACTC'ITG ACTIGAATA CCA'ITTAAAT GCGAACGAAT TCTAAATTCT GTACAACCAG AACCA'ITCTC CTGTAGCCAA ATGCCTACTC AACATCTCCA TCCCCAAACA AATTTAGTTG TI7CAATAAGC CTCTCATATI' TTACATATCC CAAACTGAAC TTCTGAATrr CTCCTCCAAT CTGTAGGGCT CTTCCCACAG CCTrCCATC TCAGTGGATT ATAACTCCAT CC'rFCCAGTT ACTCAGACCA AAACTTGG WO 00/62736 17PCT/USOO/08020 AGTTAACTGA GACACCTCTC 'TITIrTCA CAAGTCATAT CCAATGTGTC AACAAA'Ir GGTAGTGGAA ATATTGCGGG ATITITAAG AAATCAGAGA GACCGATGGG GTrCAGGAGG ATATATTA '1TAGGTGCA CTGGCCAAGT CAGATTAACA TCCAAAGGAC TGAGCCCTGA ACAAAGAGTT AAGTTACCTT TTAAGCA'TrT TGTGGGGTGG GAGAGAGGGG TATCTGTGCA GGGGGAAGCA TACTACAGAA GTGAGAAATA AAGACAGTTA 5 TCAATrrAAT TGAGACATGC ATI'ACATCAT TrC'rACT TCAAGAAGAA ACATG FTG CGACTTGAGT TI1ATCTGTCT AGTGACCTTG CAGCTGCACA GCTAGAGAAA CAGGGTCT7C ACAATGCCTG GGAAAGGAGG AGAGGTAAGT CTCACTAGCC ACAGAAAAAC AGGCAG'ITAA TfITAAAGG GCTCCAGCTC TTTCTCYI17C TCAGGGGGAG T-TGGGTITG TT1ACATACAA CTGAGTTrCC GC'ITACACAT TATrAAT= CTITTAATTC CTGTTCCAAA AGAAGCCAGA TACAAAAGGT TACATGTI'GT CTGATTCCAT TTATATGAAA CATATAGAAG 10 AGGTAAATCC ATAGAGACAG AAAGTAGATT AGAGGTTCCC AGGGGCTGAG GAAGAAATGG GGACTAACTG =TATAGGGT ACAGAGTT CTTGTGATAA AAATA TITTG GAACTAGATA GACA ITGT TAGGCCATTC TTGCATTGT7 ATAAAGAATT ACCTGAGACT TGGTAATJ'TA TAAAGAAAAG ATGTTTAA FT GGCYTACACT TCTGCAAGCT TrACAGGAAG CATGGTGCCG ATATCTGCTC AGC'ICTGGT AAGGCCTCAG GAAGCTACA ATCATGGCAG AAGGTGAAAG GGGAGCAGGC ATATCACATA GCAAAAGCAG GAGCAAGAGA GGGATGTGGG 15 GAGGTGACAG TCAC=IIAA ACAGCCAGAT C'rTGTGAGAA CTCATTCACT ATCATGAAGA CAGTACCAAG AGGATGGTAC TAAATCATI7C ATGAGAAACC CCACCCTCAT GATCAAATCA CCTCCCACCA GGCCCCACCT CCAACACTGG GGATTACAAT 'PTGACATGAG AYTrGAGTGA GAACACGGAT CCAAACCATA TCAGAGATGG TGGTTATACA ATGCGATAAA CGTCACTGGA TTGTACACTI' TAAGATGGTT G=JIATGTr GTGTGAACrI' CACCTCAATA AAAAAAAATA TTTAATGTAC ATI'CAGCCAA AAGAAGA'TT GGAATAGGAA AGGTCATGGA 20 GATATATI1AA CAGCCA=TG ATGGGTGGTA AGGAAAAGAG TGGTTAT-rAG ACTGTITGT GGCCCTCAAA AGGTAGAACT AGATCGAGTT GGTGAGCATT ATAAAACCAT CACAAAACCC TGGAGAGAGG ACCCAGTGCT GAAGAACCGT TTGCCTGCCA TGAGACATGA GGGAAGTACC AGTGAATGCC A I1GAAAGCA GCATCCCTGG GTCCAAGGGA TGGTCAAAGG ACCACTACCC AACCCTTCCC TAGCCTACGC CTCCATTACA GATGACCGCA AGATTTATI17 GCTCATFTGCT GCCAACCAAG GCTGCACTCA CTGCAG ITGC TATCAGTITA TCATGGGTAA 25 AAGGAATGTG CAGTAGAGAA CTAACTAACT GCCCACCTAC CTCCACAATC CTATCAGGAC AAATCACCAT GGCTCACATr TCCTTACATT1 TGGCATGTAA GCCCCT=TA CTGTCTGTCA TCTATCTCCT ACACAGTTCA CCTAAACTGT TCTCTCCTGA CCCAACCITrG ATTCATCC CAAATGCTrC C FJGCCATCT CTGGGATTCC TGTMTCACC ATCACCAAAC TCCCCTCAAT CTTCCAG1T CCTGT7CAAA CTITCTCCT ACCTCCTIrGC TTI7GTCATTA GCCCGACTGC CTCCCTAGGA CATCACTTCC CCTGCAGATC TCTCAAGATG ACAATATTTA 30 TTCTCCACAC AGCACATACT TCAGGGTI'GG AAGGCAGGGG CAATCTTCTC CTTTATAATG AGTGCCTCTT ATATATGMT ATT'CATCTGC CCTCTTGTAA AACACACACA CACACACACA CAAAGAAGAA ATAAAATAAC TCTG=CTr TGAAGCT-'GT GACACTGAGA TAAACCATCT CACTGTCCTC A'rTGTAGTGA CCTCTCAACT CCTCATGCAA GATrGGC'Tr GGCACCTAGT TCCTGATCTT CCTTTCCCTG TAAGCACTTC TCATAGTCTT ACGGGACTTC ACCATCCATG GCACAACCAA TACCACAGCC CAGATCCTCA GCTCTCCAAT GACNFTTCC 35 TCCACTAGAC TrGAGCTACC TCCTTCCCTA GGCACAGCCT CAACCTCGAC AACACCTAAG ACTGTACCGT CTCTAAAGTC ACATGTTCAA ACACTTCACT CTTTAACCAC TGTCTCCTAT TCTTrGCAAGT GTATTGCTCA AGTATCTCAT TGCAATGCL17 TTTAC'FrCTA CCTCATTGAA CCTCCAGGCC ATTAAACATT TCCrrATI-C TAACCATCAG G'TTCTCCTT ACTI'GTITGT TTG=IA TrT G'ITTC'rfTT TTTT PJTGAGACAG GGTCTCACTC TGTI7GCCCAG GCTGGAGTGC AGTGGTATGA TCTCGGCTCA CTGCAGCCTC CATCTCCCTG 40 GTTCAAGTGA 'rrCTCATGTC TCAGCCTCCC GAGTAGCTGG GACTACAGGT GCATGCCACT ACGCCTGGCT AAGA'T=rGT AYTITTfA GAGAAGGGGT 'IMGCCATGT TGGCCAAGCT GGTCTCGAAC TCCTAACCTC AGGTGATCCA CCTGCCTCAG CCTCCCAAAG TGCTGAGAfl ATAGGCATGA GCCACTATGC CCCACCTGGT TTCTCCTJ7AT TFAMICAAG TCTATGCTGC ACTATTAAAA CTGCCTTGAC AAAAATTATA ATAGTGAGAA AATTATGACA GTGAAAGAGA TCTGAAATAA TCAACCCCCA TCTTGCC1T ACCTI1CCAGA CTGCCCTTAA 45 TAATT1CCTGA GCTTGGGCCA AGCTATUT GGCAGAAATT TAGMTATAG TIT7AAATGAT AATAGCCCTT CTCCAAAACT AAACTGCCTI' TGTAAAACTA ATAAAAGACC ACCAATGAAA GGTJ7AGGAGG ATGAGAGGAG CCTGAATTCT GCTAAGGTGT AGATGTAAAC AATTACCAAC TGTTATTCCG GAGGTCACAA GA'TrTGCAAC ATCGCCAATT ACTCCTGCAG ATAACAGCAC TATCATAGAA TCTGAT-FGGC C'mTGAGAT GTCTITCAG ATTCTTACAT TTCAACTGGT GGCTCTACCT GGACCCATCA ACAAGTCCTG TGGCTCCACC CAGAAGCAGA 50 CTTAACATGC ACAAGGACCA =ITCCACAC CGCTATGA'IT GCATCCCAAC CAATCAGCAG CAACCATTCC TCTGCCTGCC AAATTATCCT TGAAAAATCT TAGCCYI'AGA A=IIGGGGG AGGCTGAT CAGTAATAAC AAAACCCCGG TCTCCCAYI1? GGCTGGCTCT GCATGAATTA AA'ITTrCT CTATTGCAGT TCCCATCTTG ATAAATCACC 'TTrATCTGGG CAGCAAACAA AAGGAACCCA TTGGACAGTT ACACTGTTGG CAGATATATC TTGCTTCCAA AATTGGATT TTG'TrAATG AATnTAT7CT Gr1TCTTGA TATTACAAC TGTGAATGTT 55 GTGTCTGAAT TCTCn7ITTf TCTTGTTGAA AAGAACTATA TTGCTACAGC CAGTACATAC AGATGGATAG CTAATTACTC AACACGGGGG GATGTGACCA TCACCGCACT GTGCAAATGA ATGT7ACCCA PITGTCCACTT TTCCCAAACT ACATAGTGTT ATATGGTATA TGACCCAATC AACGGTGGCA AAGCTCCAGA AATACCACAT AGACATCAGG GACACTTAA ACTAATCAGC CTATAGTCCT ITMCAGTAA TTTCCAAACC TGG'FrGTGCA TCCAAATCAC TTGGTAACAT TAAAAAAACA AAAAAATATA CACGCAACAT TCGCTCCCAA TCCTACTGAA 60 TCAGAATATT1 TrrGGGTrGGT TCAGGAACAT TCAGGAGTrT 37CAGGGTCC AAGGTTTATA TAATTGAGG TCTCTC TrG AGAAAAGGAA CGTAAAAGCG TC1rGC'II ATAGATCTI'A CAAAGATGTA TI'ACCATGTA AACACATTCC TAGGACCCAG GCCCTTGTAA TTTAAAGGTT TATCTAAGTA ATGGGCCCTG AAGCTrAATT 'rrCA'FrATCT TCAGGGCAAA TTACCTGTGG GTTAGGG'IM AGGAATATAT CTCTCTGTGT ATGTGTGTGC ACATT1AGCAT GTACGCTTGT GTGGA'TT TfITfTT TTTFT C TGAGACAGAG TCTCGCTCTG 65 TCGCCAGGCT GGAGTGCAGT GGCGTGATCT CTGCTCACTG CAAACTCCGC CTCCCAGGCT CAAGCGATTC TTCTGCCTCA GCCTCTT1GAG TAGCTGGGAC TATAGGCACG CACCACTATG CCCAGCTAAT T'TrGTA3TT TTAGTAGAGT TGGGGTTTCG CCATG'ITGGC CAGGATGGTC TGATCTC'IT GACCTCGTGA TCCACCCGCC TCCACCTCCC AAAGTGCTGG GATTACAGGC GTGAGTCACC ATGCCCAGCA CTrGTGTGGA TGTJTI'AAGC TCCCAGGTGA GTGAATACAA AACTAGATCT TTCCCTTCTG TAGCATCTGT ACTG'TFACT CTATGCATCT 70 CAATAT1T TC LTTAGTA Tc'IT-rccTT TTCTCTCTTA TTACrTCCTC TTGTGCTATT 'TrTACACCTC CTITITAAA AAATTTIC CCTJ1'ATTT CTATTGACCT TTAGCCCTCA CAATGATTCC TACAAGCCCC ATTCTGTAA ATGGGGA FTG AAATAAT7GC TGGACTITG AGAGATAGAT ATATTAAATT GCAAACTGGC AGTAGTGGGG GCAG'rTGATA CATAACTAGG 'JTIAAAGTC TAGCCTrTCTG AGACCACTCA TTCCA'ITTGT WO 00/62736 18PCT/US00/08020 GAAAAGTGAT TCTACTTCTI' ATTATGAGCC AAAATATGCA T1'CATTCACC CATGCATTGA 1TAY~rCATT CAATAAATAT TT1GTTGGATG TCCACTCTGT ATCAGGAATG TGCTAGGTTC TGGGAATACA GCAATGAACA AGGTAATITTT TCCCTACCCC TAAGGAACT AGAGTrAGT GGGGAAGACA GACATTAAAC AAACAAFrGT GCAAGTAATA ATCTATAATI' A'ITTATTACA ATI'AAAGGAA GGAAGAGACA TATGGATTAT GAGGGCATTA 5 AAGAGGAGAC CTAGTGTAAG TAGCCAGTrC TCGTGAAGGG ACATGTATTA GTTGGAGTTC TCCAGAGAAA CAGAACCAAT GGTGTGTGTG TGTGTGTGTG CGTGTGTGCG TGTGTGTGTT GGGGTGTGGG GGTGTGGTAT TITPATAGA AATT1GTCTCA CACAATTATG GAAGCTGAGA AGTCCCATGG CCTGCTGTCT ACGAGCTGAG AACCAGGAAA GCCAGTGGAA TACTTCAAAG TCCAAAGGCC CTGGAACCAA GAGTGCCAGT GTTGGAAGGC AGGAGAAGAT GGGTGTCCCA GCTrAAAAAG ACAGTGAA'I17 CACTCTI= GCTCTACATA GGGCCTCAAT 10 GGGTTGGATC ATGGCCACCC ACAITGGTGA AGGCAATCCT CTrAGTCTAC CAATrAAATA CTAATCTCTT TGGAAATACT CTCACAGACA CACTGAGAAA TAATGTTTTA TCAGGGTGAT AGAAATCT7C TGGAGTTAAA CAATGGTGAT AGCTGTACAA TCACATACAT 'T=rAAAGGG TGCG'IrAT GGAAAGTGAG T1T-ATCTAA ATAAAATrC TAAGAAAGAG ACTrAACACA GAGATAAACA TAAGCACATr TATI'GTCAAC CTT~rATAGTG TATGTCAAA TAGGTCTGAC ATAAGC'IAA ATAAATATAT ACTTrAAAAA TTATAAAATA ITrAAGTTA 15 TAATI17AAAA TTCTCAATAA AACTCAAACA CAAACCACAC TGGTATfCA CACAGCTAAT FTCTAATGCA GTTTACATAA ATATTTACAA CACTTAAACA ATTTCAAAGA AAATAACACT GTATTCCATA CATAGCCTGA TCACAGTAGT TGTrCTCTCT TA=TCCCAG AGTI=CTG CCCCITAAA AGAACCTCTG CTGTTCTGAT CCTTATCACA TCTCTG ITTT GACTGTIGGC TTTrGTTG CCAGTGTTCA GCCAGAACTT CTCTGAAACT TIFJ=CAA CACATGCTAA GTTAATGGAA GTGTAGGAGA GT=TGAflC TCACACTCCT CAAGGCTAGA 20 GCAGC'1TTGG CAATTACTGA CTGAGAMTTT TTCATFGCCA GTGATCAACT GAAAACTGGA GAT-rCC=TG GAA'I1GTTAA ATCTGC'ITAT AAATAAACAT AAATGCTTGC TCACACAGGC ATTrCCTCTCT TCCAGAGCAC CCTAACATAC AGAAGAAAAC AAATAGGGAA TAACTATTAG ACATCTTCAT TCGTrAAAAA TCTACCAGAT GACTCTTA CATGGTGAGT TTCTATTGTG AATITAAAAT C VrCCATAAT ATACAAGAAT TATG TI7ACA TATCATATCT GACAAACATC TITGTAGGAA TGCAAAGCAC ATCCATCTI1 CTGTATTrCTT TTrCCAACAAA 25 GACAYI'CATA AAATTATACC FITGTGTGTr TGCA TI'ATG CTITATFAG TTCAAAACGT TTGGCCTCAT GGAAGT'=Ir CATCGTGGAA ACCACATATT TCTGAAAAAA TATCTGACAA TATACAAACC TTCCATTCAG T'ITACTCT CCAATI7CTAC CATG=ITCA AAAAACAACT GTAGTAAAAA CACTCAGAAC TTA'I1CTGG 'TAACATCAT GCCTTGCTAG GGGACAATAG TrCCC'IT TGAAATAAAT FTAAAACAGA TGTAACATAA =TGTTAATA AACAATGAGG GGGTAATCTA GAATAAGTAA C'IIACCAT ATCATAGTTG ACAGCATTTA 30 CAAGTTT AAGTCCCTAC CACACY[GTA TrGAATGAAG AAGTATGGAA GATTATAATA TATTCAATGC AAGTAAAAAT ATCACAATCC TI'AAGAACTC TrAAGAAGC ACTGAATCCC ATAGGGATGA AAGTGATrAA ATTGTGCATA GTAACCCTCG CACAGAGGAT TCAGTAGGAT TTGCACCATT AACAACCCTC CATGCATTITG CCTGTGGGCA TrCAACATCT GTCAITTT TAAGTFATAA TATFITAGT CATTIT=C CTCTAAACTC TGGATAATTA TTATTCATTC 'VTATGACAGC AACTGTGTAA TCAGCTGTCG AAACACTGTG AAGGGCAAAA 35 GAAAGAAAGC CACAAAATAT TGTG'TrTCTG TGCCAAGATT TTACAGCGAG CAAGGGAGAG TTAGAAAAGG AAT'rCTGAGA TTCAGAGTC 'TGGTCTCTr CACCTTrGCT TGGAAGAAAA TATCC'=CC CT~rCATTrAGC CAACACTYrTC TTGATCCTGA GAGTAGGAAA GGGAACACTG AGTC=I~CA GTT1GAAGGCC GTCC'I7GCCT GCTGGACTTT GATCTATTGA AGTGGTGATG GGTGTrGCGG 'TrTCAGCCAT AAAGGCATCT GGCATAGTAG GCAAGAAGGG CCAGAGACCC GAGGAGAGTT1 ATCTGTCTCT GTrAACTrCA GTGTATCCCT CTAGTTCCCC 40 AGATGCACCT G'ITrCTGTAA ATATAAACAT GCATGTCATC AGAACACTTA ATAUTCTGCA TACTGATCAT GACAACAAAA TGTACCTFCT AACACAGACA CTCTCACTAG GATAGACCAT GTAGGAACAT CGAATFCTAT TCAGTTAGGA CAGTGATGAT GTCTACATAT TATACCTCTG TCAAAACCTA CAGAATATAC AACACAGCAC AGAGTGAA'I1 CTAATGTAGC CTGTGGACAT TAATGAATAA TAATGTATCA ATATFGGCCC ATCAGTTGTA ACACTAATAT AAGATGTTAA TAACAGGGGG AATTGAAGGG GTGGTGGGGA GATATGTrFGG AACTCTTTGT 45 GC'TTCTGCT CAATTrCT GTAAACTTAA AACCGCACAC ACAAAAAAAG rrATrTAAT 'TI=AAAAA GTATTCAGAG GGACTTGACC 'TrCCAAATT CTCTCAAAGC AGGTCGGAGT AGTTAAGAAC ACAAAFITTA GAACCAGACT GCCAGAGTTT GAATCCTGGC TACACCACTF ACTAGCT=G AGKITTCAGA CAATTTACTT AACTTCTCTG TCTCATITC TTCATCTGTG TGATAAGAAA TAAAGTAACA GGCCAGGCCC AGTGGCTCAC GCCTGTAATC CCAGCACT-fT GAGAGGCCAA GGCGGGTGGA TCAGGAGT17C AAGATCAGCC TGGCCAACAT 50 GACGAAAAAA TACAAAATCT CTACTAAAAA TACAAAAATI' AGCTGGGTGT GGTGGCAGGC ACCTGTAATC CCAGCTACTC AGGAGGCTGA GGCAGGAGAA TTGCTTGAAC GCAGGAGGTG GAGGTTGCAG TGAGCCAAGA TCATGCCACT GCACTCCAGT CTAGGCAACA GAATGAGACT CCATCTCAAA ATTAAAAAAA AAAAAAGTAA AAAGAAAAGA TAAGAAATAT AGTACCAGCC CCTATCTCAG AGTrCCTAGC TTAGAAAAAT TCCCAGAATA TAATAAGTGC AATGTAAGGG TCAGCTATCT TCATTATTAT TATCTATCAT AAATGAAATTI ACACAATAAA 55 GCTAGATCCG TTTC'ITCCT CTCCTTCTAC AAAAAATAAA GCAAC'TTTCC AGAACAATAC CCAGGTGATG A'ITTCTCCCC TGCTCCCTCC CTAAGATKI1? GGCAAGnI7G GAGGGTTCAA GGAGAAACAG AGCATGTAGA GAAGATACCT CTCTCATAAC CA'TrGTGAT TTACAAGTCT TACCTGA1TC 'ITGAACTI' AAAGGATGTA AGAAGGCThI' TGGTAGCTTC CATCTGATTC AAGG='~GG CAGCTGCTGT GGAATACATG AGAACACTAG GTAAAGCACT GTC'ITCCAAC ATGAAGAGAG AAAAATATGT GGAATGTI'CA ATGGCATGCT TJ7GTATAAGA 60 ATGCAACTTA CCTGGCAGGA ACAAMTFCT TTGCTGCAAA AGAAAAGACA AACAACCATT AATTCAGACT AAATGAC'1T TAAGGATATA TTAAATCCAG ATACAATATG ACTTAATlCA TCAAGTG1TG CAAACTCGAT GCT-rCAGGGC CTCTGTAATA ATCAGAGCAC AAGCATGGCT CTGTGGCATC TAGGGTAAAA TGCAAAGTGC ACAGCCATCC AAAGGGCATA GCAGCTT1CCT AATGCCAGCA AATAGCTACG GGGTCATCTT GCCCAATTCA GCTCCCAAT7T 'TTCATGAGA AGTCCAAAGT CTTAAMTAA ATGTGAGA'Tr TCCTATITTrG TAAACGTCAG 65 AACTTAACTC AAAAATGTTT TAAGTACTCT TAAACATGTA AGCCAAACAA ACCATGAGTG TAGTCAGATG TGCTrCCATA 'rrCCVrATGA GAGACTCTCA AATrAAGCC TGTACTCCAA ATAAATCTCC TTAGGAAGAA TITATCCAT TfTCCTrAGA GTGCTCATCA TGGCAGTTCC ATTGCACAAT TCCGGGAGGC ATCATATAAT TCAACATGAA TAGCACCCCC TGGAGTTGTA CAATATTAGG CACGACTAAC ATTTTTATTT CCTGAAACAC TI'CCCACACT GAGTTGTACT ACTAACTCTT 'TCTAATAC TTCTGCTTAA TTATACTGCA YTTATCCAG 70 ATTCTAATT1A TTG'TTrAAAT CAGTAAGCAA GACCATGACT TATCAATGAG AAAGAAATGT ATITTFCAAAA ACAYI1TGA AGTACA'rrCA TAAACI1?CCT CACCTTCCG TAAGCA'ITrC CGAAGCCAGA GGAGAAATGG TGCTAATGTC AGGAGGGAGA GTCCAGCAGC AGAAAGTCCA GCTACCAAGG GAATGI17GGA CTCAGTGGGA GCTAAGGAAG TAAGAGACGA AGAAAGGTCA TGAGGAAGAA TTGATG ITAA AGTCTCTCCG TCCTGTCCCT WO 00/62736 PCT/USOO/08020 189 TTGGCC'1TTTCTGTACAT TCATTACTAG GAGCAGAAGA GCTATCTAGT TrAATACAAG AAGCAGAGAT GTGGCA'FrAC AGGCC'I=rGA GATCTGCTCC AAGCCACC'IT TGAAGCTATIT TCCACCAI1G GCAGGCAGAA CTCTAAC'rG CCAAGCTCGT TCACAATACC ACACCACACC TTGGTTAATA AACACTGCAC TTGCTTGCTC TCTTGCTCTC ACTCCCTCTT GTITCCATT TCCCCT1TrCT CCTCTCCTCT CTCTGTCTCC TTTTCCAGT 5 TGTCAGAATT CTACCCnI7C CATCAACATG CAAC'ITCTGT TTI'CTCTA TCCCCATACA ACTTAATATI' CACAACTTGT CAACCTGGGC GAACT1T7CTG GTrrGGATAT AATGAATAGT TGATTACTGT AACAAGATAG CTCCCCCTTT TTC'TAA TCACCAGACA ACCACCATCA ATCAATGCAT CACC1I7CACA GGTAGGTAGC AGGCCAGACC AGTGTCCTGT GGCTCCACAT GTCCGAGCTG CAGAGCCATT GAGCGTCCAT CCTrCAGGAC AGGCGAACTT1 GCACACAGTG CCAAACACGG GCTCCCCACT GCAGCTCATG TfrGATCTrTC CCGGAACTGC 10 CAGGCTTGAA CATI'ACCA CTGCAAATGT TAGGTACACA GGCAGAGTTT CAGAAAAATC TACTGGAAAA CTTCCAAAAC TTGCTTAAAA GTCAACAATG AATGTAAAGT GTAAGCGCTA CTTAG1TTC AGCATGTAGG AAATTAGGAC CAAACCCCTT TGGGGCAATC TAGGTrCAGA AACMTATGA AGTATrGAC CTGTACCCTA AAAAAGTCTG CACTCAAT7C TACC=GGCA GGAAGGAACC TCTTCTGTCC A'I1GTCCCTG AGATGTGCAC TCAAGTTGAG TTGATCCATG TAATTCAAAT CCCTCCTCAC AGCTGAAGGC ACAAGAGGAC TTGTAGGTGA 15 AT-FCTCCAAT AGGGGAATGA GCACACCTCA CCAAACCC= CGGGGGCTGG TGGACAGCAT CGCATCTCAC AGCTGGAACA CAGGAGAGAG CAC'TJAGAA G ITrG'I=GC ATCTCCAGCA ATACGTITCC CAAGGTAACC AAGTTCCCAA GCTCTT1CAAT AGTrCT=T1 ATCTTAAAAT AAAATAAAAA CAAAGACTGT ACCTTCACAT GTGGGCTrFCT CGTTGTCCCA CTCCCCTGTG GGGCCACA'IT GGAGCCT= GGATCCCTrC AACACAAAAC CCTGCTCACA GGAGAACTCA CAGCTGGACC CATAACGGAA ACTGCCAGAA GCACTAGGAA GACAATTCAT 20 GTAGCCTCGC TCGGGGTTGG ACAAGGCTGT GCACTGGAAA GCTGAGACAT CAAAATGATG GTCAGAAAAT ATTGCAGTGG AACTAGAGAG TACTTGGCGT TTG'rTGAGTG AACCCAGTTC ATTCAAGCAA CACTTrGGAGA ACTGAAGATT1 C'ITATAATT CCCTGGACAA ATGGGAAGAT GGCTGTGT TCTTTGAA'rr TCAGCCCCCT CACTGATCAT GGCACTAATT AAAAGACTAA TTAATCAGAA CATTAGTrCC TGAGCACTGT TC FTCTAACA CACAAAATAA ATTATGGTCC AAGGAAAGAT TTCACGCAGT CTGAGGACAA CATATGGGTC ATGGATGTrT 25 ATAGATGGTG CCAAAAAGAA AGAAAAGAAA GCACCCCTAT AAAATTTGTC TG1TVGCAG TITGGTTrT GTGTTATGTT TTGCTACTGG AAATCATTCT GTGCTGG=T TGGCTAGGAC AAGGCCAGTG CCTGATAGTA AAAACTGCTI' GT'ITTCAATA TCCTTGCTCT CAC1TAAAG TGAATTAAAA TTrACTGCTT ATATATGCAT CAATACTATC TCTGTAGCTG ACACCATGCT TGAAACAGTC TCATCACTGC TAATFATGAG CCAYTTCAGA AGACAGGTGT GATGAGAGTT TTACATTCAA ATCATGTTCT CA'rrATTCTG CTITCCGAAT TITCTAATAT 30 GATrCC'ITA GATTAAGAAT TCTGTCTATr CCATGCTAAT GTCTACAAAG TTTATCAGC ACATCACAGT TAAAAAAAAA CAGCAAAGAA TTCATTCTTA ACACATATGA TC='~CCCT GGCCAAACAT TAGrrCTlTr AAATGAATCT CAAAGATACG AGGGTTrGCTC ATCAAATCTG AITI'CTATAG TVAAAGTGGG TATFGGTT TITITCACT GTCCAAGYI1 GAAGATGG FT GTL'CTI1'AAG AAAGTATAAA TCGAAGGATC TCAAGCTTAC C'CACAAAC TGGGATTTGC TGTGTCCACT GCCCTTGAGT GGTGCATI7CA ACCTGGGCTG GTCCCTGCAA 35 CATGAAGCCT TCCTCACAGG TGAAGTrGCA GGATGA'TrG AAGGTGAACT CTCCAGCAGG GGAATGGCTG CACCTCACAG AGCCATTCTG AGGCTGGCGG ACGGCCCTGC ATGTCACAGC TGTAACAAAT ATACGCATTG ATA ITAGCAC GGCCTAGAAT TAGCTI7GCCC A'ITTCCAGTA TGGGTTGAGA GAAAGAATGT TCACAGTAAG TCTCCATGTG GAACAACTCT ACCY=ACAC GTrGGCTCT CGTTGTCCCA ATTCCCAGAT GAGGTACACT GAAGGCTCTG GGCTCCCATT AGTI1CAAATC CTCTT1CACA GTCAAATGTA CAGGTTGTGT TCCATGGGAA 40 GCTTCCAGGG FI=GGAAAC A~rCCACGAA CCCATrGGCT GGATYGTCA CAGCATCACA CTCAACCACT GAGGAITM1A AAGAGCACCA TGAA=1IAC AGAAGAATGA TCTTTTCACT TCCTATI'GAG CTGGGTGCCT AACAGAGTGA GGAAGCTGCC TTCAAAGGGT AGATCCCAAA GTCCTATGTC AAYTCTTAGG GACATGCACA GCCAGAATAA AAGCTT~AT TC'TI=CAT GGATATTCTA TCTT'CTGA TTCCA=1I GCCTATGCTG AGTGGTCTCT AATCTATGTT ATCATTTACG TGAGGTAAAA A=IAAAAAA AATAGATI'CC AGATI'AGGAG 45 TTATGACTAG TACTGACATA CGTAGGCTAT TCA=TATTT TAGCCCATCA GAGCCTGAAG AACTGATTr TCT'IT'fTG GCCTCTGGTT CAGAAAGATA AAATrAAGAG AGAAAAAGAG ATACTAAGAC TGC I1GACTA TCATGGTCY'r AAGTTAGTCC CATGGCTTGG AAAAGT~rAAA CAGGGAAACA AGATGAGAAA TCCATFGAGA T17CTAGAGC l=ATTGMr TATGGTCTCC CTTACAAATC ACCAGAGCCT CAGAAACACC CA T7CAAGC ATAGAATAAA AAAACCTCTC TCAACCCAAG CAGGTACTGG GT7GGCAATA TACAYTGGCT GAGAGAACAA 50 ATI'GTATTAA AAACAAAAAC AAAAAAAAAA C1TCCCTGA AGJ=rGAAA ATGTAAGTTG AATCAAAAAA CAGAAGCAAT GAGGGATGAG TTACAGAACG TTCTGTGCAT TCTCAGAGGG ATFTACCATIT GCAGGCTGGA ATAGGAGCAC TCCATT1CTCC AGAGGACATA CACTGCATGG TCTCCATGCT GCTTGGCAGG TAACCCCTAT CACAGCTGAT AGAGCAGGAA GAAYJ7GTAGC TGAAGTICC CAGTGGGTGA CTGCAAACCA GG=TCCATG CTCAGGGGAT TCCAGGGCTG TACAGTL1CAC AACTGAAAAA GAAACCCAAA TCAGTTCTGC TCATCTCTCA 55 CCMIIAACAG ATAAGAACAC TGGAAACTAG AACTACAG FT TGGTTr=T TITTIAGT TTAAAAATTT ATAAAATTTC TAATGGAATT TGTAAAATTG ACTGTAA FrC TACCCC'T= CTTTTATrCA AGAAAATGCT GATCCATAAC AACAACAACA AAAAAGCAGT GATGACAACC ATAAAAAAGA AATA'I7GAGT GATATGGGGA GAGTAGTGTA ATTGTGTTTA CCTCAAAACT GTlCAAATTA TATGAACAAA CACAGCAAAC TTAGGTACCA CAACAAATTrT C FrGTTACTT TTCTCACAAC TGCTAAAAAT ACTACAGTAA GC'rrCCAACC AGGATGAGAA 60 CCATI'CACAA AGCTATATT CAAAITTAAG TACTAGAATA CATTrACAAAT TrAAAACCC TAATGCTGCA CTGTCTACTA TAGTAGCCAC TATCTGTGTG GCTACTCAAA TrAAACTFG AA'FrCGTTrGA AATCAAATAA CAMTAAAAT TCAG'ITCCTC AGTGTCACCA GCCACNTC AAGTACTCAA TAACCACATG TGGCTCATAG GTACACACTG GAAAACACAG CTATGGAACA T=CCATTAT CACAAAAGCT CTACTGCACA ACGCTGTGCT AAGGAATC'JT GGAGAGAAGC TCATCTAACT CTCTTAATGT ACAAATAG GAACTGAGAC CTCATTTCAT 65 TCAAGTGACT TGCTCCATGC TACACGGCTA GTCATTACAG AGCCAGAGGC CAGAGCATGA ACCAAGATAC CCTGGACTCT GTAACTCACT CATTTCTACT GCAACGTCTT G'ITACCACCT AGATGAGGTG AGTACATGTr CCTCGCAGGG ACACAGAATT ACAGTTTA TF GAATGTGTCC TGTGTGCCAG GCACCATGTA ACCATGAGCC TATGAAG'JTC ACACTAYI'AT TATCCTCAY1' TTACAATGAG AAAACTGACA TAGAGAGTTA AACTATCTTG TCAAGGTGCC AAAATAAATA ACTGGTGAAT CTAGGACTCA AACCCAGCAG GGTCTGACTT CATAGTCTCA 70 GCTCACGATC ACCATATGAC ACCATCTGCA CCAGGGAAGG GAAGGCATGC AGACCTGACT CTAATGCCAG CTAGGACGTG AGATGGTGCT ACCATCTCAA GTGAAGAAAG AGGCAAGAAC CAGACTTACT TTGCTCACAC TTGAGTCCAC TGAAGCCAGG GTCACACL17G CAAGTGTAAT TATTGATGGT CTCTACACAT TCACCGTGGC CACTGCAGGA TGTA11TGGTA CAGGCAGCTA CGGAAAATAC AAAGCATGAT GAGGAGGACT ATTACTGTGC WO 00/62736 PCT/USOO/08020 190 TTATACTGAG TGCCTTTGAT TTTAGAATCA ACAGTGTGCA ACAGAGACAT CAGCAGTCCT ACAGAGTGCC ATAGACTTTA ACTGAAGTGT TTACAAAGT TCCAAATCTG AGTTTCAGGC CCACCTATCC TAAACCTTGA TGCTAATGTA TAGCTGTGGC TGGCACCTAC CGTAGAAAAT TTACTTCTTC ACAAACTCTG AAGACAGTTC CCCTACCACA AATAAACAAG TAATTAAAAT ATGTATTGTG TGTGTGCATT TTTATATGTA AAGAACTACA 5 TATTTGCCTA CAGTATTTAT ATATATTA TATATATACA TACACACATA TATGTGTGTA TATGTGTGTA TGTATATATA TAAAATGTAT ATAAATGCTG TAGGCTATAT ATATATACAC ACACACATAT ATGTGTGTGT GTATATATGT GTGTGTGTGT ATATATATAC ATATCCACAT ATTCTTGCCC ACATTCACAC AAAACAGCAA AAGAGAGAAA CTTTAGCAGT TAAACAGAAT CTTGGAAC ATAAAATGAC CACAATAGAG AGCAGTT GCATGCTGTA AATTTGCCAA GATGCCCACA CACTGAAACT ACCTCCCACT GCTGCCGCAA ACTCCCTACC 10 TGTGTAGCAT AGGGCAAGCT TCTTCTTGCT GCACCTCTCA TCATTCCACA TGCCCACATC TITTTCTCTC TTGATGTAGA TCTCCACGCA GTCCTCATCT TTGCCTAT TGTTGGGTTC ACCTGGAGCC CAGTTCTTGG CTTCTTCTGT CAGAGGTTTC TGGGTTCCTA CCCAGACCCA CACATTGTTG ACTTTTCTGA TTCCAATCCA GTAATAACTT GGTGAATAGC TCAATATGGA GTTTAGGTAC TCAATCTCTT CTTGTTTG AATTGCAACC AGGTGTGTGT ACCTTTGCTG ACAATAAGCA CTGGCCTCAT CATAAGTCAT AGCTTCCGTG GAGGTGTTGT 15 AAGACCAGGC TCCACTCTCT TTAATGAGAA GCACTAGTGG GAGAAAAAGA AAAGAAATGG TAGAGTTTGG TACTGTTGTG GTTAACTCT GACAACTGTG CTITTATTG TCTTA TT GGCAATGTTT GTGACATGGC CCAGACTTT CTCATCTTTT CAAAAGTAAG AAGTACGTAT GAAGAAACAG CGACTTATTG TTTATCTCTT TTGTGACTGC CACCCACTAG GTACCT7ATC CACACTCACT CACAACATTA TAGTATACCC ATTTTGTAGT AGAATAATAA TCAGAATAAC TAAGCTTTAT TGAGCACTTA GTATGCACCA AGAAGCACTG TATGAGGTAC 20 TTTCCATGAA CCATGCTATT GAATCCTCAC AATGCATCTG GGAAATAGGT CATTATGATC CACACTTTAC ACTTAAGGAA AGGGAGACAC CAAGAGGTAA AGTAAATGAC CCCAAGCCCA GGGAAGAACA CATTGCAGGT AGAGGTCAAG GATGCTGCCA GATATCCTGT GCAGGACAGC CCCAGACAAG CAAGGATATT TCAGTCTGAA ATATCTATAG TGCGAGAATG AGAAATCT7G GTCTAATGGC ACTGACTTAC CCAAAGTGAG AGCTGAGAGA AACTGTGAAG CAATCATGAC TTCAAGAGTT C'TTCACCC AAAGGTTTAG GCTTGAAATA CTTTCCTGGG 25 GAGATAAAAC ACAAAATGAA TTAAAGAAGG AAATCGTGGG TAGCTAGTTA CATTATTCTA CCATGATGTT TAAGGCAGCA TCCTAAGATT TTGGGCAAAG GACACTAGTG CAATAATCTT TATTTCAGAG TTTAATCAAA TAAATAAACA AATTAAGA CTTTCATTAT TTAGGTCAAA GAGAAAAGAC AGGTTTAGC TACAATACAA TAAGAGCTTG TACAGATGTG GTTTTTATTA GAAGGCCTTT TGCATATCTG TGTTTCATGG CCCGAGGCTG CCCTTATAAA GCGTTCTGCA CTTACCGTTT TGGGAAGCAG TTGTTCAAAC ACAGGATCTC TCAGGTGGGT 30 ATCACTGCTG CCTCTGTCTC AGGTCAGTAT AGGAGTTTTG ATGTGAAGTC AGCCAAGAAC AGCTGAACAC TACTTCGGCT GAGGCCCTTT TATAGGAGGG AY[GCTTCCT GTGAATAATA GGAGGATATT GTCCACATCC AGTAAAGAGG AAATCCCCAA TGGCATCCAA AAACTTTCCC GGGAATATCC ACGATGCTTA AAATTACAAT GATGTCAGAA ACTCTGTCTC TTGAAGCTAC TTCACCTTTG TCCATGCCTT TATATCGTAT ATGCAATTTT ATTAATATGA CAAAAATGCA TGATTTTAA TTATAATAAC ATAAAGTCTA TGTCTTTAAA AAGTTGTAAA 35 ACTTTGCTTG TTAGTAGTGT CTCTCATGTA GTTGTGGTAG TAATTAGAAT TTCAGAAACA GAAGGAAACC AAGAATAGGT TTGTCATCCA TAGTCTACTA CCTTCAATTT CTCATTCATA GCTGTGGATA ACCAATCACT ACTCATTTTT TCTTCCTT TCACCTGCCA ATTCAACATA TTTAACATGC ACTGTCTCAC AGAGGAATGA CTCACAAGGT AGATATTAAT CTTCAGATTT TGCACGGCAG TTATGCCTAA ATTAAAATAT TATCTAAAAA TAATATCTAA CACTCAAATG GTTAAAATAA TGCCTTATTT TAAAAAAAGA AAAATGGGAA ATAGATATTT 40 ACATCTGGGA AAGTTTCATG GTTTGTTCAG TGAAAAAAAT AAAAAGGAGG CCAGGCACAG TGGCTCACGC CTGTAATCCC ACCACTTTGG GAGGCCGAGG CAGGCGGATC ACCTGAGGCC GGGAGTTCAA GACCAGCCTG ACCAACATGG AGAAACGCCA TCTCTACTAA AAATACAAAA TTAGCTGGGC ATGGTGGCGC ATGCCTGTAA TCCCAGCTAC TCGGGAGGCT GAGGCAGGAG AATCGCTTGA ACCCGGGAAG TGGAGGTTGC AGTGAGCCAA GATCACGCCA GTGCACTCCA GCCTGGGAAA CGAGTGAAAC TCTGTCTTAA AAAAAAAAAA AAAAAAAGAA 45 AAGAAAAGAA AAAAAATAAA ACGGAAAACT ATATATATAT ATTTAATTGG TCAAAATT GTTTAAAATT TTTGAAATGT TAATGTGCAA AGAATAAAAA TTCTTCCACA ATGTTAACAG TGACTAACTC TGGATGGCAG GATTTGGGAT AATTTATA TCCTTCATTA TTATTTTCAG GATTTTAAAG TTTITCAA TTTCCCTIT TTTCACCTTT ATAGTAACAA GAATACAGTT TAAAGAAACT TGTCTCTAGG CCAGGCATGA TGGCTCATGC CTGTAATCCC AGCACTTTGG GAGGCTGAGG TGGGTGGATC ACCTGAGGTC AGGAGTTCCA GACCAGCGTG 50 GCCAATATGG TGAAACCCTG TCTCTACTAA AAATACAAAA ATTAGCCGGG GTGTAGTGGC GCATGCCTGT AATCCCAGCT ACTGGGGAGC CTGATGCAAG AGAATCGCTT GAACCCAGGA GGCAGAGGTT GCAGTGAGCT GAAATCACAC CATTGCACTC CAGCCTGGGC GACAGAGCAA GACTCCATCT CAAAAAAAAA GAAAAAAAGA AAAAGAAAAG AAAAGAAATT TGTTTCCAAA TGCAACAGAA GGAGATGTAT GTGGTATCCT ATATTCCTGC TCTFCATTTT GACATTTCTT CTGGGTGATT GTATACATTC CCCATCTCTG CATCT7ACCC TATCTAAATG 55 ATGGTAACAG TAAATGGGGA TCATTAAT TTCCATATTC TGTAGGTTTT CAGAGCTCAA GTCAAGCTAA TATTCTATAT CTACAGCCTT TCAAAATAGG AGGTCTATCT AAAAATGTAC TGTCAGCAGA CCTGAACGAG TAGTGGTAAA AGCCTCGTTT TTCTC AC TTGTTAGCAC TGGTCTTTCT GTGTTCATAA AGATGTCAAG ACCCAAAAAA AAAACAAGAA AAGAGAAGAA AAATTCCAAA AAAGACAACT GATTAGAAAA AAATAACTTA ATTAACGAAT TTAATTCAAC CCCTATCAAA AAGCATAGAA TTTATTCCCT CCACCTTACC ACTCTCTTAC 60 ATGATCCAGA TACTGACATT ATrCCAATrC TTATCCCAC TTTACTTAGC TCAATGTGGT TGTrGCTTCA ATAAATTCAG AAGAGTAATC ACTCATATAG TGTTTATTTA GATTAGGG CAGAATGTCA AGTTGGGTTA ATACATTATC TGTATGTATT TTATTrAA TAAAGTATGA ATACATAATC TGCTATTT1 AAAAAGCATG GTCAAATGTA TAGAGTAGCC AAATCTTAAA AAACAATTTA TCTTCGATAT CAATAAAGTA CCTAATAATT ATATTGCTAA TAGAAATTAG TCGTTAACAT CCCTAGATAA CTAACTAT TATTGCGAAT TTTTCATAAC 65 TAAGTITATA GTTTATCTCT TCCCCTTTTT AAAATTAGTT CAAAGATATC TAAAAATAGC CCCAGTGGTG ATGAAGTTTC TATTTACTT ACATATATAT GTCCTGGACC CCCAATTATA ATCTCTAACA TTTATTGAGT GCTTACTATG TGCCAGGCCA TATTCTGAGC ATTTGTATG TTCACCTATT GATTATTCAA TCCGTACAAC AGCCTATGAA ATAGGTACTC CTATTATCCC CATTTACAG ATGAGGAAAT TGAGAATCTG GGGATTTTAT CTCATTCAAA AGCACAGAGC TAAGGGTFGA AACCAGGCAG TTGATATCCA GAGCCCACTC CCTTACCTGC 70 TACTCCAAAC CATGATTTCT TTrGTTGTTA TGCCCCGAGA TTCC17GTTC TACCCAAGTT TCCTGTACTC TTCTTGCCCT CTTCTTCCTG AGACATCCTT GACCATCACA GCTCTCCACT GAGATAACTG TGTCCTGGGT TCTGAGACAT GGGGGCTGGA AGGGACCCCA GGGACAGTGA GCAGTAGGGA GAGGATGCAG TGAGAACAGA CCCTGGATCC CCGGTGCATA GGCAGGGAGA AAGTGGACAA AGGAAAAAAC AAGCAAGGCA GGTGGAGCCA WO 00/62736 PCT/US00/08020 191 TGCCTAGGTA AAGTTGATCC CTAAGCCACA GTTCCCAGAA GTTCCTGATT CAAAAGCAAA YPTTCTCTAA GGTCAAAGGG CAAACTGA'IT A31'CTAAATT CTAAACTGAT TAITTCTAAA nFGAGAAAGC TTCAGGGAGA GATCCCAATA TTCGAAGGAT AAGAGAAATG AGGAGTGGAA GAGATAGGTG AGTAACAGTA ACTTAAATGT AGACTATATA TAATATATAA TATATGTAGA GTATATATAT ATAATTACAA TATATTATAT ATGTGGAATA 5 TATATATTAT TFATATATAT TTATATAT'IT TATATATATA GATA'TI1A TArITTATAT ATAAATATAG ATATI'TAT AlTIATATA TAAATATAGA TATITATA TATATTATAT ATAAATATAT GTAAAATACT GTGAAAGAAG AATAGAATCT TGAGACCTCA AATTCACTAT GCCAAAGGGA AAGT7AAGCT TGGGAAATGA GTCATGCAAA AACTGCCTTC CTI1GT7CC CAAATACCTG TAA'TrCACA TGCTTACT ATCTTATATA AAATGTAGAT GTACTGAGCA TGAGATCCAT GCATAATTTC CCTCTAGTCC CTTCTTITA CATGTAAAGT 10 GTAGACTCAC TGAGTGTTAC AGAGCCTTGC CACAATGTAA ACACTTGTCT CA'ITGCCAAC CCATC'ITCG ITATTrTrCT TCCCCTCCTG CTITGCTC'IM CCCCTCTAAA GATGGAAGT7 CCCAAAACTC TCTTTGGAAA AAGCGCAGGT CACAGATCCT ACAGTGATT7 GTGTTTC1TTT TACCTGGGAC AAAATAAACC TCTAATCTGT TGAGATATGC TI7CAGTTACT =L]GG'TI7A CAATATGTAC ATGTATGTAT ATAATTATA TGTATATAAT ATATGTACTT GTITAACCA GAGGTATGTr ATrCAAAATC CATFCATCCT TACAA'ITACC TGCATTCTCC 15 CACAGTAYI17 TCTGTGTCCC TGCCCCCGAG GTTGTCACTG CAAATCAGGT ACATGGATAC TGGGAGCTGA TGGGCTCCCC TCTGGCTACC TGGGCTGCTG AAGGGGCCAT AGACAGACCC AGC TITCCTC TCGTGGAGAG GCCCTGGGCC AGCGCTGCGT GGGAGTGGGA TTACAACCAG ACTATAGCT CT7CACCTGC 'TT=CCTAT CAGGATICA TAAGAGGCAA ITGCTTGTTT TTGAGGGTG GGGGCAAATC AGGGGGAGTT GAAGAGGAAA TTGGGTAAGA TrTGAATAGT TGGGCATGTT GAATA'ITATG AATATCATCT CCCTCTTCAA ATAATCCAAA 20 ATATACCCCC AAGAAACAGG CTGATTAGAG GTGCT-FCAAG GCTCCACTGA ATCTCCCAAG CTCTGAAGAT GTAGCTAGCT GTTACCGGAT TGCCGGTT CAAGCCTCGC CTCACATGGA CCCTCTTGGC AGYTTCTCGC ATGGGGGAAG CATCCGCTAC ATAGATGGGA ATGAAAAGAG GAAAGAAGAC GGTGCAAACT CAGGCACACC CCGGTGTCTG CCACCAGTGC TATTAATCT CTGAGGTGTC ACCCTT1CCTG GCT1TTATTGT CTCTTCCTGG AAGTCTCTTG TCCTCTCCTC CACACCC'Tr AATCAGGCAT CAAAGACTIT7 AACCAGTTF GCTGTGTGCC 25 CAGGCCCACT CATTCTCACT TTrATGGCAA AGGGAGTGGG AGACAGAGAG ATAGCCAGAA AGAAGAGATT GGGGACCCCA AGACAAATGT TAGAATITA ACCAAGGCCA CCCTGTGGAC AGGAGATTAT TGGGTTTAGT GGAAAGCAGC ACTGGCCACA ACCACACGTG GCAAAAGCAT CTATCGAGGA GTGAAGTTAT ATTTGGTGAA TGTGACCGGG AAGCAGGGGC AGTGGTGTCC TCCTGCCTrC CTGAGGCACT CTGTTCCCTr ACCTCTGCGA AGGCT-rAKTTr TACCCCTGAG TGCTrAG'Tr TGAAAGCCTF AGTI7CCCTCT CTCCCATAAA AAAGCTCTAC 30 TCTGCTAACA TCTAAGYI'AC CTTTGCAGAG TCTTrAGGTAG AGGGAGGAAA TCCCAATAAA GATTCCACCC TATCTGCAAA ATACAAACAT GGTAT1TT GCATrCCCAA AATTGTGAAA GAAAATGTGT ATCACCACAG TAGAGAATGG CAT~TTGT FTGATCAAAA CCTAAATATA ITrGATGAAA ATGTGTCTGG TrCTAAGITT ATTTCCCAGA AAGCCATGTT TACTCAC ITG GAA'rITATAG ACATCTTATA ATATCTGAGT CGAGTAGGAG CTCCGGGCTC TACCTCACTC TTrCTCCCA CACCCAGGGG GAAGTGTAGG GTrCTCAGAC TPTAGAATAA 35 AGAGGAATCA CCTGGACAAC TCACCTAAAA TGCACATCTr CAGGTCTCAT ACTCAGAGGC TCTGACTCAA CAGGTCTGGG TGGCGCCCAA GAA'r=rGGGC TTTAAATGAG TATCTCAGAT GA'ITCTAATA CAGAATGTGT AAGATGACCA GATCCTATCA CACTTAGATG TA'FrGGCCTA GGGCCACCTA AC'ITGGAGAA AATGTTAGTA AGACCCCGTG GTTGGTGCTC AGCTATAGGT ACCAGAATr TGATCAAAAT TL1ACTATCAT TGTGACACT11 CTCTI'CGGAA CTGGAAGGCC AGAACCCCAC TTGTAAAGTG CTGGGAAAAT ACAAGGAAAA TI'AGGGTGA 40 GTAGCATTT GAATTCTTAC ACATGGAAAG TAAATGTATA AGAATrT = A CCAATAAAAA AAAAGCAAGA GAGAATAGCT GCTAAAGAAT TAACACAAAT ATGTATATAT TAGTTA1TCT CTITCTCCT CTGATTCCAG AGGACTTGT AA ITCCACTA ATrT=CTrG AGCYFCCAGG ATGATCTGAG ACT7GAATTT TT'CATGTGCT TffGCTTrCC TA'ITrGGCAG CAT=rATCT TGAAGTIT7CC GCTITCTGCT TGGGGACCTA AAAACTAACT AATGGGAATT TCTTCAAAAT GAGCAAACTC TGGTGAATJC CCAAAGCGGA AGAAACAAGT GAGGATCGGG 45 CTGGTI'AATTr AAGAGAACTI' TTCCTGAATG TAGCCAGACT GM~GCCGAC TGTI'GTTAAC ATGAGGGAAG AAATACCCCT GGAY1IAGA AGAGCCCCTrI GTTTGTITC CTTGGCCATI' TGTGCTGCTT GTr7GTAAG TCAGAAATTI CCTGAAGGAC TA ~rATTAGC T'ITGTTCTCA CGTCAGAAAA CTTCTGCTCT GGCCACTT AAACATATAA CTTGGATT ACTGTATTAG AAAATGTAAC AATTACAGAC AGCACTAAAA GGACACCAAA GGGCAAAGAA AATGGGTAAC TrITr=CT TCCCCAAATC TAAAATAGGT GATITTGGAG AAGTAGGAGA 50 AAAACCTGGA T=~CTAGAT CTCTIT7AGAG CTCAACAACT GATATAGTrA ATTATGTAAG TCTITIGATAT TTGGAAATGA TTGGATTAAC CGGATAACAA TGAATATI'A AATACAGTGA TIGGCCAGG AGCAGTGGCT CATGCCTGTA ATCCCAGCAT TTGGGGAGGC TGAGGCGGGT GGATCACCTA AGGCCGGGAG TTCCAGACCA GCCTGGCCAA CATGGTGAAA CCCCATCTCT ACTAAAAATA CAAAATTAGC CAGGCGTGGT GGTGCAAGAC TGTAATCCCA GCAACTCGGG AGGCTGAGGC AGGAGAATTG CTTGAACCCG GGAGGCAGAG GTI7GCAGTGA 55 GCCAAGATCA CGCCATITGCA CTCCAGCCTG GGCAACAAGA GCGAAATrFCC ATCTCAATAA ATAAATAAAT AAATACAGTG ATh7AACACA AGAGATITCT ATICACACT AATGAGCTCT GTCACTGGGG CAAGCTTCTIT TGCCTCAYI'A AGTCTCAGAT TTCCCGAGAG CTTATATr TATACCAAGA GTGCTTTACT ACCGTCTCTG CTAGCTGTGA CATAATATGA CAAAAGGTAT AAATATGGGA AAAGGCACTA A MTIATATCA AAGCGTTCTT CGTTTITCCT TGCTGTGAAG TTAGCTA ATAATI'CATA AGAATATACC ATAMIIAGAG TGTITACTAT 60 GCATGGGCCT GGCACTTCAC ATACATTGCT TCITFACAAAT TTTACAAAGT GAAAGGTAGA TA'I1AATCTC AYVI1ATGGA GGACAAGATA GAGATCTGGA GAGGTTACAT AACTrGCCAG TGTTITTCA GTTAATAAAT GGTAGGGTGG AGATT1CAATC TGTGTTACTC TAAAGTCCGT GTCC'TTIA TTGGCTCCAT GCCTACTCAG ATTTAAATCT CAGCAGGGAA GTAAACC'IA GTITIACAT GAGAAAATGT TACAGCAGCC TTCTCGGCTT CCITTTACCCC CATCCCAGTT TCACGAGCTT AGTGCCTAG ATCGGGTrCC TTTAGAAGCA GACCTCGAAA 65 TAAGGATGTG GGTGCCAGTC ATrATTGAA AAGATGATCC CAAGAAAGCC TAGTAGGAGA GTGAGGAAGT GAGATGGGGA AAGGAAGAAA CTCCACAAGA AGTGTGT7AA TAAGCAGGTr ACCGCTGTGG GCAGCCATGG GGCTCAGCTG CACTAACAAA CTCTGTCTAG TACAGAAAAC CTCAGGGTCT CCCCAAGGAG GGGCAAGAAG TCTGCCTAGG GTATATATCC GCCAACTCAG TCACTGGCTG AGAGCTGATC CTGGGAGGGC ATGGT7AA'IT CCTCTGCACT TTCAAGTGGA TTCCTGTGGT CAGAAAAAGC CCTCTACAAT GAATITCCAGA TGC'ITGTATr 70 TAAATCTGAC ATGATCTGAA TGCTGTGTTG GGACAGGGTG GGCGTTA'ITA GTITCTGTC ATTACTGTAA CAGATVACTA CAAACCTGAT GGCTGCAAAC AACACATATI' TATTATGTCA TAGTL17GTGT GGGTCAGAAG TACAGGTT1AG CTCAACTAGT 'ITCTCTGCTC TAGG ITCAC ATTGCCAATA TCAAGGTGTC ATCCAGT~rGG GCTCTTCT'FG GGAGGCTTGG GGATGAATCC ACn7TCAAGC TCA'ITCAGAT TGTTGGCAGA ATCCAGTrCC WO 00/62736 PCT/USOO/08020 192 TFGTGGTTGC AGGACCAAGG TCCCTGTTGC C'rTGCTGGCT GTTGGCCAGG AGTCATTCTT AGC'ITCTAGA GACTACCTGT ACTCTCTGAC TCGTGTCTCC ACTTCACCITF TCAAACCAGC AGCGGCTAGT CGAGTCCCTC TCTTCAAATG TCTCCAACTG TGCCTTCACC TCATrCTCC TCTGTGTACC ATGTCTGCCT CTACTGCTTG TAAGGGCTCA TGGGA FrACA 'TGGATITAT TCAATCCAGG ATAATCTCCA TNITIAAGG CTAGCTGACT 5 AGTGATCTTA ATTCCATCTA CAAAGTCCCT TCCAATAGTA CTGTATTAGT CCATITTCAT GCTACTGATA AAGACATACC CAAGACTGGG CAATTCACAA AAGAAAGAGG 'TrTAATrFAGA TITACAGTTC CACATGGCTG GGGAAGCCTC ACAATCATGG CAGAAGTCAA GGAAGAGCAA GTCATGTCTr ACATAGATGG CAGCAGGCAA AGAGAGAGAG CTTGTGCAGG GAACTCCTCT T'I=AAAACC ATCAGATCTC ATAATACPITA 'I1CACTATCA CAAGAACAGC ATGGGAAAGT CTI7GCCCCCA TGATrCAA'rr ACTCCCACCA GGTCCCTCCC ACAACATGCA 10 GGAAYI'CAAG ATGAGA'rrrG TGTGGGGACA CAGCCAAACC ATATCAAGTA CCTAGATTCA TGTTTGAT7A AACAACCAGG GAGCAGAAAT CTTCAGGAGT GGGGGGCATC TTAGAA'17C TGCCCACCAA GGCTGGGCGC GGTGGCTCAC ACCTGTAATC CCAGCAC1T GGGAGGCCAA GGTGGGTGGA TCATGAGGTC AAGAGATCGA GACCACCCTG GCCATGGTGA AACCCCA'IT CTACTAAAAA TACAAAAATr AGCCAGGTAT GGTGGTGGGC ACCTGTAGTC CCAGCTACTC AGGAGGCTGA GGTAGGAGAA TCACTTGAAC CCAGGAAGCG GAGGTI7GCAG 15 TGAGCCAAGA TTGCGCCGCT GCACTCCAGC CTGGGAGACA GAGCAAGACT GTCTCAAAAA AAAAGAATTC TGCCCATCAT AGTAGGCTGT CCTACAGAGA CATAACCCAG GAATTAGGTG AATGGCTAAC CTAAATTAGC ACTGTGATGT G=IICTGAC TTIGGTCCTIA TAGCTCCrCT GCITrAGATGT GGAACTAATC CATGAATGCA AGGG'TTGTC TAGAGTITA AGTGGGAGTT AAATATCCAA AGTACAGGAG ATATTATGGG TGCCTCATCC ATGTCCCCTT GGCKITTATC TTTCITrGGAT AACCCAACTC TATTAGTT TATATCTCAC TrGTFCCTAT 20 ACTCTGTGAA CTGATGTCCC ATAAATAGAC ATCATIT GCCAGTCTTC 'ITGAACAATA A'rrACGATA TTAATCTAGC AGTTATCATT AATTGGCCAC TTCACATTAG ACACAGCACT TAGGACITAA GAATACCATG TCATPTGATC ATCATAATAT GGTCAGGAAT TAAGTATGC TATCCAAATI' TTACAAAGAA GGCACTGAGG G FrAGAGTr AAATAACTTG CTTAAGATGT CATAGCCTGT AAGTGACAAA ACTAGGACTC AAATACAGGT CCATCTGACT CCAAAGTCTA TGTT1CYIGGC TACCACACTG CCTCTCCTAC AAGTGACCTG TGGTTIACT 25 ACTATATTCA CACTCTACTA AC'IMACCAT CTCCCATGAG TCTGTCTAGA GGAGGGCACA CACAGCACAG AAAACACATG AATGCAAAAT AAGGAAGGGC CTAC'ITACTA CACAGAGCCA TTCTAATACC TGATG'ITTGC TCTAATCCAG T1TACTATT AATTAGTTGC TGGTGCCCAA GTTFACTG AGAAATGGGG ATAA'TTrGG AAGTCATAAT GATGCCTTCT TCTCATAGGG TA IIA IM GTI7GTTGTAT CTCCAGGCCC CAACACAGCC TGGCTI1TAG TAAATGATCA AAAATACCTG TTGAATGAAT AAATGGAGTC ACCTGAAACA TGTTAAACAT 30 TTGTTCATGT GTCCTAATCG TGGA1TTTCAG GATAGTAAGC ATCCTAAAAG GAAAGCATGC ACACTGTTCT TGCTACATTA ATTTCTCACA ATATAAAAAA AGAAAAGCAT CTGAAAAAAG CTGCCAGCCG CTGTGTCTCC TAATATCAAA CTGAGCACAG ATATGGAGAA GCTAAGGGAG AGGGATGATG GGCCATGCCT CTAACCTCAT CATGGCAAAA GTCCTGGGGG TCAGACCCGA GGAGAGCAGG AAGTGTCTTT TGAGGGATAC AITT7CCACAG TGGAAATAAT GAGACTTAAA TAAATATTAT ATACACAG IT CAACTGTIT TATGTGTAAA GGTAGTAGGT 35 TTTCACAGTA AGGAAGCACT TCTTTrT TTGMTGAG ACAGAGTCTC GCTCTGTCTC CCAGCCTGGA GTACAGTGGT GCTATCTCGG CTCACTGCAA TCTCTGCCTC CTGGATTCAA GTGATTCTCC TGCCTCAGCC TCCCGAGTAG CTGGGACAAC AGGTGTGTGC CATT1ACACCT GGCTAATIT TGTATITA GCAGAGATGC GGTTTCACCA TGTT1GGCCAG GCTGATCTCG AACTCCTGAC CTCAGGTGTT CTGCCCGCCT CTGCCTCCCA ATGTGCTGGG ATTACAGGCA TGAGCCACTG CACTCACCAA GCACTTCTAC TGATAGCATT TACAAACCCT 40 TCTTAGAATA TTAAAAATT CTAAGAGAAG AGTAAATTGA GCCTTCCCAA CTAATACTAG GAGGTTATAA CC TCATACC AAAACTGGAC AATGCTI'GCA CAAAAGAAGG AAGCCAATGA GGCCACCTAG AAGGAAGACT GGGCATTGGG CCCAGTGAGT CCTGGAAACC TCATCTGTGC CAGCCACCCC GGCATGGCCT GTATGAGTGG ATGAGGGTGA CTrGTCCACA GACAATAGCC ATCTAGCTGT GATAAAGGAG TCAAGGTAGT CAGCTGCATC TC'TCACCT GTITGCCAAT GTrACACAGG TTGAAAAGCT AAGGTr7ATG TAAAGCAAGC ATCAAAGATG 45 ATGAAATGAT CAACCTGACA ATGAGTACTA TGCTGCA'ITG TCCAGAAAGG AACTGTGGAA GATTTTGGGC TGAAITI'CAA AACAGAATIT CCTCACTCTC TGGATGTFGG CTTACTTGGC CITTGATGTT CAGAGGTGGT GCC'T'GTGT TGTTGAACAA TGTTGATIT GGAGAGAAAA CAGAGTTrGAA AAACCCACAA GTCATTCCCT GGGGAGTATT ACCGGAATAC AGAGGATAAT TTCAGCAAGC CAGCAAGGCC TCATCTCTGC TTCTAATAGA TAGGAAGAAA GGAAGAGAGG AACAATACTT TITAAGAAG CTCAGCT=A TCGCCTTATC TCATAGAAAG 50 ATGCCTCCAG TCTGTCTGGC TAAAGGTAAT TGGCATGGGA AAGTC'TI7AT CTGTGATTCT AACAAGTGGA ATGYI1TCCCT TCATTAAGAG AGCC'ITGTCT GGCT-TGGGGA AATGAAACAC nITCTCCGAT ATGAGTGGGC TGTAACCCCT GCTACTAAAT ACTCAGAAGA AATAAGGCGG TT1GTGGAGCA GTCAGGAATG AGTCACTTGC CTCCCTGGAA TATTCAGAAA ACTGAATCAA AAGTACATTC TrCTGGGTTT TCTTAGTCTA ATAGACTAAG GGTCTCTACT 'ITGTIAAATT TCTGGGAAAC AGCATAGAAT GGGAGAAAAA ACTGGTCACT GTAGTCATGC 55 AAATCTGCAA AACAAACAAA AAAGTCTGGG TATTGCTGCT AACTAGCTAT GTGACCTTAA GCAAGGTATT AACTCTCTCT GAMTTTCAGG TTCTTCATCT GTTAAATAGC ATATCTGTAA AATGGGAA'rT ATTTTCATAT CATAATGCTG TAGCTIAAA AAATAAAATA AAATGGATGA GATAATCAGA ATTAAAGAGC CTGGGATATA TAGF'TAATAT ATAGCAGCAT GTAAAGATCC TGTTAGAAAT GCTAATIIA CAGITAACCA TTTGGAGATG ATCCGCCAAA GCTGCTAGTG TAGAGGCAAC TGAGAA'T7G CCTGTCCT7C AGAATATGAA TAAATAACTG 60 TCAATGATGT CTCAAGCCTA GAAAAACCTA TCCATCTGGA TGGGTGGGAA ATrCTAGGC TAGTATTGAG AAGCCCAT'rr CTITGGGAAAT AGGTCCTGGA CTGAGTGAAG GAAAAGAAAC AGTAAAACCC ATGGTAAAGC AGCAAGGCTC TCTAGAGGCT CTGGAGAGGA TGAA'JTGAAT TCTAGAAGAT GAAGTAGGGA AGACGCTTTA CCTTC=GTG AAATGGATI'C AAAGATTCAA AGACCTTCGG GAATCTCCAA TrGTATAAAT GGCACCATAG CTGTATGTTrC CATGGAACAC TAC'TrCCCAG AGATGCCCAG TGAAAAAAGA ATGCCACAGT CAAATAAGT 65 TGGAAACACT CCA ITATGTG GCCACCTCCT TGAAGACTCT AATGCACA1T AGCATG'rrAA ACAGTCTTGA GAAGTCCTGC AGAGCAGAAA TrGCTTCACA TCTGCTAAGC CGGCAGTTTC CCAATATACT TGA'ITATGGA TAGTTC C'ITACAACAC CATT1CTCTGA TATGCTTCCA ATGACATGAA ATAAATATAT ATGCATGAGG TTCT'FCATTA GGGCATACTT TI'AATAGAA AATATTGAGA ATAATCTAAA TATAAATGCA CAGCATI'AC CTTCTGCA TAAACTATAT ACAGGCATAC CTI'GGAGATA CTATGGGTIT GGTTCCCACA ATATCTCCAA 70 AACCACATrC GGTIT-ATGA CCACTGCCAT AAAACCAGCC ACATGAA'IT TI1GGTTI7CC CAATGTATAT CAAAGTTACA 'TTMACTAT ACCATAGTCT A ITATATATA CAATAGCA IT ATATCTAAAA AACAACGTAA ACACCTI'AAT TrAAGGCTGT GGCTGGTTG A TITCTACC CAGACCACTA AAACMTCT CATATCAGCA ATAAGGCTGT FrCAC'TrCT TACTATITTT TGTGATAGCA C'ITICCTIT CCTTCAAGAA TTrTCC=~ WO 00/62736 PCT/USOO/08020 193 CTA'rTCACAA TfrG ITGAT ACAAGAGGAC TAGATI=AG CTTATCTCAG MTAAGGTGT 'PrACATTGTT AGCTAAAAAT GCTAATGATC ATCTGAGACT TCAGCAAGTC ATAATCTT GCTGGTGGAA GGTCTTGCCT CAGTGTTrGAT GTCTGCTGAC TGGGTGGCTTr TGGCAATrC UrAAAGTAAG ACAACAATCA AGTI1GACAT ATCAATTGAC CCTTCCTGTC ATAAATGATT TTTrrMCT CTGTAGCCTG CAATGCTCTTI TGATAGCATT 5 TTACCCACAG TAGAATTI'C AAAATTGGAG TCAATCC [Tr CAAACTCTGG TGCTG=IrA TCAACTAAGT TTATGGAGTA TTAGAAATCC C'rGTTGTCA TTTCAACAAT GTTCACACCA TCTTCCCCAG GAGTATATrC TACCTCAAGA AACCAC'ITTC 'ITGCTCATC TATAAGAAGC AGCTCCTCAT CCACTAAAGT TITATCCTGA GAT'rGCAACA A'TCAGTTAC ATCTTCAGGC TCTACTCTA A'rrCTAGTrC TCTFGCTGTT TCTATCTCAT TTGTGCTTAC M~CTCCGCT GAAGTCTTGA ACCCCTTAAA GTCACTCATG AGGGTTGGAA TCAACTT= 10 ACAAACTCCT GTTGATG31?G ATA'IrGAC CTGCTCCCAT GATTCATGGG TATTCTTAAT GGCATCTAGA ATGGTGAACG TITCAGAAG GTITCAGTT GGC'1TTGCCC GGATCCATCA GACGAATCCC TATCTATGGA AGCTATAGAT TI7ATAAAATG TATTTC II1 'TTGTGGGGG CATAGCGTCT CACCCTGTCA CCCAACCTGG AATGCAGTGG CACAGTCATA ACTCACTGAA GACTCAAACT CCTGGGCTCA AGTGATTCTT1 CCACCTTGGC CTCCCAAAAC ACTGGAITAC AAGCTTGAGC CACTGTGTCT AGCCCAAAAT GTATATCATA ACTAATGAGG 15 CTTGAAAGTC AAAGTGACTC CTrGATCCAT GGGcrACAGA ATGGACGCTG GGTTACCAGA CATGAAAACA ATACTCATCT CCTCATACAT CTCCTTCAGA GCTCCTGGGT GAGCAGGCCC AT-FGTCAAAT GAGCAGTAGT ATCTTGAAAG AAATTTI1 TCTGAGCAGT AGATCTCCAC AGTGGACTrA AAATAGTCAG TAAACTATGC TGTAAACAGA AGTGCTGTCA TCCAAGCTCT G1TITCCAC TGATAGGGCA AAAGCAGAGT AGA ITTGGCA TAATT1CTCTA GGGCCTAGG ATITTGGAA TGGCAAATTG AGCATTGGCT TCAAC T1T TrrrTIT 20 TTITITGAG ACAGAGTCTTF GGTCTGTCAC CCAGGCTGGA GTGCAGTGGT GCAATCTCGG CCCACTGCAA GCTCTGCCTC CTAGGYI7CAC ACCATTCTCC TGCCTCTGCC TCCTGAGTAG CTGGGACTAC AGGCACCCGC CACCATGCCC GGCTAATITI TTGTATITA GTACAGACGG GGTCGCCA TGTTAGCCAG GATGGTCTCG ATCTCCTGAC CTCGTGATCC ACCCGCCTCG GCCTCCCAAA GTGCTGGGAT TACAGGCGTG AGCCACAGCG CCCAGCCTGT C'VrCAACTrA AAGTCGCCAG CTGTGTTAGC CTCTAATAAG AGAGTCTGCC TGTCCTTTCA 25 AGCM'1GAAG CCAGGCATCA TrrCTCTTCTC TAGCTATGAA AATCrrAGAT AGCATCTTCT CCCAATAGGA AGCCA'TTT TATGCCCTAA AAATCTGTCG TTGGTGTAG CCACCTTCAT CATJ7GATC'IT ACCTAGATCC GCTGGATAAC TTACCACAGT GTCTACATCA TTACTTCTGC TTCACCTrGC ACTITATGT TATGGGGATG GCTCCTPCC TCTAACCTCA TAAACTAACC TCCACTAGCC TCACATTCTT CT=TACAGC TTCCTCGCCT CTCTCAGAGT TCACAGAATT GAAGAATGTT GGGCCTI'GGA TTACACTG GMIAAGGGA ATGCTGTGGC 30 TGGMTGATT TTCTATCCAG AACACTAAAA CTTTCTrCAT ATCAGCAATA AGACTGTC ACTrCTrAC TATITITGT GATAGCACTT TTCC'1CCT TCAAGAATTT TrCC'TrCTA rCACAA'Tr GACCGTTTGA TATGAGAGGC CTAGAT1TA GCCAATCTCA G'IMACACCA TGCCTITC ACTAAGCTTC ATCA'11TrAG CTI=rAT AAAGTAAGAT GTGTGACCCT TCC'Tr7CATT TGAACACITrA CATGATGATG CCTGGCTTCA AAGC FTGAAA GGACAGGCAG ACTCTCTTAT TAGGGGCTAA CACAGCTGGC GACITI1?AAG FTGAAGCCAA 35 TGCTCAATH' GCCATTAGAA GCCATTGTAG GGTrrAATrAA TGCCTAAT 'TrTAATATTA TGGTGTCTCA GGGAATAAGG AGGCCTGAGT AGAGGGAGGG AGATGGGGAA ACAGCCAGTC ATCAGAGCAC ACACAACAT7 TATCAATI'AA G'I=fATCACC TTGAGGGCAC AGGTCATGAT A = CAAAAC AATTACAATA ATAAAATAAA AAATCAT1'GA TCGCAGATCA CCATAACAGA TATAATGATA ATGAAAAATr TGAAGTATTG TGAGAATTAC CAAAACGTGA CACACAGACA CAAAGTGAGC ACATGTCATT GGAAAAGTGG TGCTGATAGA CTTACTTCAT 40 GCAGGGTTGC CACAAATACT CAATCTGTAA AAAA I1CAAT TATCTACATA GTACCATAAA AACAAGGTAT ACCTG'I=AT ATAATCAAGA CCAACAGAAC CCTAGAGAAA ATAGCTCACT CCCTAGCTCG GAGACATTCT AACCAACATA CACTTACCTT TC3TITIGCT GTGTACAGAA TTCAAATCCC TGTCTCAGCA AAA'I1GCAAA GTATCAAATG TCATGTCCAT CTAATACTCA AAACTGCAAA TGTTAAGTCT TGTAAGCCCA GAGACCACTG TATATACAAG TGTTGCTATA AGCATTAG'IT CTTCTCCAAA GAAAATAGTC CACTTGGTAG AAACAAACAA 45 AAAGAAAAAA AAAGAAAGAA AAAACATI' TTACAAGAAG ATTCAGTCTC FTACCTACAT AAGCAAAAAT ATGAGATGTT CTCTTATCAT TTTTCCATCT ATC IATAAT C'TGGTGCT GACTTAGACA CTCATTCC TTTGTACG TGACCATGTA AAAGTTCAAG TCAAGAAAAA CTTG1T=GA CA'1TTGTI= GCTGAGTGAT GGGTCCCTAA AAGAAATTTG GCTrTGC=I TGAAAAGTI7C AGCATGATAT TGTGTGAA'IT 'ITTCATGGCT AATGATTT AGAACAGTTG TGATGTG'I= AGGTGT=~A AGAATATGAA GCATTCAGTG GTTTAAGTrrG 50 GTTGTTATAA AATGAAAGAA TATGAAGGAA AGCCYrCTTG TCTTAGAACA CACTGA FTCA CAAATAAGCA GCTTCTCTCA AAATGTrGTA ATTACAAAAA TTCCAAGGCA AATATAATAA ACTCCTTFGTC GGTGCTATGT CTAGAAACTT AACAGCCCCA AAGAAAGTCC TGACAAGGCA AAAAATATAT ATATATATAC AAATTGTGGA AGCAGGGTGT TGAAAGAAGA ATAAAGACTA TATAAGGACA AACTG'TrfAA AAGGGAGGGT ATCCTTGAAA GCTTGACACT TGACTC'TT17 GACGAGGCTG AGGGAAAACA CTCAGTTfrCA TAGAL1GCTG GTACGGATGT 55 AAAATAGTGA CATCCCTATA GAGAGGAATT TGGCAATATC TAGCAAAAGT GCTTATGCAT TrAT-rC=~G ACCTAGTAAT CCCGCT17CTA GGATTAGTGG TGAAGATACA CCTCAACAAT AAAAATATAT ATACATTAGG TTATTAGrrA TGG'TrAATT FITAATAGCA AAATAT1T7AA AACAACCTAC ATGAACAAAT AGGAGAC FA CTGAATAAAC TATGGTATAT CTGTACAATA AAGTGCAATT CACTTATGTT GTTAAMJGT TCCAAAAATC CAGAGCCAAA GAGTAT1TTGT TATGCTCTCT TT1AGTATAAG AAAGGGGAAA TAAGATATGT GTGCATCTGT 60 TTATITTGT GAAAATAAGT ACAGAAAGGA TAAGTAAGAA ACTAGTAAAA CTAG'FrATCT CCTAGTGYTA GTAGAAATAG AATGAAAGTG AATTAGGCTT C'TrGAGTAT ATG'ITrATAT ATAGT=FGA CTMTGAATT ATGTFTATGT TTACATAGTC AAAAATATAA A'ITAATCAAC AGAAATAACA AAAAAAGAAG AAATCACAAG CT'17AAAATT TAATACAAAC AGAAATAAr GAATCTAACA GTATATCAAA GTGATAACGT AAACTCAGAA GAAAAAAACA TAATCCAACA TACCAGTGGA ACACAATATr CTAACTGTAT ACAITCAGTG GTTATAGTCT 65 AAGGACAAGA AAAATTGCAA AAATATCTTG AAC'=AGCT TGTAGGAT~r ITATrTGGTAG CAATACTAAT GTACTAATTC TGAAATTAAT G'ITCGTGTAT TATAGAATTG AGTAAATGAA TAAATATGTT GATGTrArrG GGAACTAAAA 'JTATCATTCT GGGAGTAGAG AAATATAAAT ATGGACTTGG CAAATGAAAC AAAGACCTGC AGAGAGATAA CCATATAAAC TCATTATITM AAAAATI'ATA AGTGTCCTAG CTCTG FTACT GAAAAGGCCT AGATTCAATC FrATC FrGAT AGACAGGAGG GCACCCC'= CTCAGAACAT GGTITTCCAAA TGCCAYFCTC 70 CATTAAAAGG AACAAGGTCT TCTTGGAGAA AAGACTGAIT CTAGGTCTGG ATTAGGTAAA GTACAACGTr AGTCTGGAAT TTCTTGCTGA ATCAGAAGTA AGAAAGTGCT CAAAAACATG GGAACATGTC ACAAACACAC GTGAGGCAAC TTGAATCCTC ACTGGCCATA TrAGGACAA TCGAGCATCA AAAAAAAAAA AAATGTTGAG AATAATGGAT TCTAACACTP AAAACAAAAA ATAATCCATA GCCCACAGAA GGGGAAGAGA GGGGGAGCTC WO 00/62736 PCT/US00/08020 194 TTATrrfACAG ATGAATATCA AATAGCAAAG ACAGAAGAAA TGACAGAATT AGAGAAACAT CATrGCAA AACACCACTG TAATAATCAA TT1CAGGCAAG TATTAYTAAT GGATGTA'ITA CTATTGCGTA AAACCAGTTG GGGAACAGGA TAYTCATACA GTCTGAAGGT GTCACCCTAA ACATAACTrFA TTACAAGTGG AAAATGGTGC CITTACAATG AAGAAATCTA GCAGAAACCA TCTTAATCTA GTGATCAAAC TTAGTATCAC CAATAATGGA 5 TCATACTGAG TCATGTGTCT CCTAATATGA TGCACCAGGA AGGATGCAAC GTCATGAACG TrGTA'rrGTr TFTGTATTCAA CAGACCACCC AGGGTAAAGG CAGC'TCTC ACTTACTAAT CAGAAT7GTI' GGtTTAATT CATMTGGAT 'ITTAAGATTT CTTAC'=CT TGTCAGCTCA GAAATATT TAAGATGATT ThrATCPTT ATTCAATACT TrAGC'rrGGA GAACCATlCA GAGTTrCTAA CTCATTGTAT TGCCAAAAAT AGAAAACAGC ATGGTI1TC F TTGAAAATGT CTAACTrAA AGTTACTGT GTGTGTCACT CAGATTCACA TAGCTTTT 10 GCCTAGTAAT GTAGTATCAT GTGGCAAGGC TATAAAAATG 1TfACAATCT 'T~rATPTAAT ATGACTCTTG AGAG'ITrAT CTAAGGAAAT AATTGAATAG TAACAAAACA CTATTAACAC AAAGCATAGC AAMVGAT GGGCAACCAA ACACTGGAAA CAACCTAAAT GTCCATTACA GGAATCATrT ATGAAGCAAA CACTAAAATA TrATrGTGA AGATrATGAG AACATAGAAG ACAGTTATGA GAGTAAAThI' GAAAACCTGA ACACAAAACT TACATATACT CCAA'FrGTAA CTTATAAAAA ATACGTGCAT ATAAGGATAA AACAGTACAA ACAAAAAAAT 15 AGTJ7GCGTTA GATI'GGTAGA ATTATGGCTC CT=TGCTGT CTAATT TCC'IPACA TITT7GATACA TrrA=TAAT =rAAT=TA AAATTCAAAA GAAT~GCCA CTCATC'IMG CCACTTCAAG GAAAAAAGAA ATGTG'TCGA TTATTCTGTT CTTAGTATAG TITTGGCAAT TTCCTCACGT GTAAAAAGAG AATACTATTA ATAATITCAG TATCTATAAG ACAATATAAA ATI'AAAGAAT CTAGCCCAGT AACTGGTACA TGGAACGTAA TT~AATAAATC ATI7ATGGACT YTTTCTCA CACCCAAGTA GGGAGGAATC AGTGGTCCCC TAGAGGCCCA 20 GTGTAGAGGT GGCAGCACCA ATCCCTAGGG GAGAAGATCT TGGTGATGAT AA17CCTGAG CAGACAGTTA GCTGAGAATT] CAAGAGCAGA AAAGTAAGAA AGAAACAACT TCTTGCTAAC ACCTITCCAC CCACG'TrTCC CTGTTCTGTI' GTACTCTGCT TACCC'=CA TGGATGGAGG CAGAGGAAAG AGAACCAAGT TTFGCTCTTAG TCATTCACTA TGT7GYIAA TCTGCCTTCC ATCTITCTrA TCAGTTCAAA TTAGAATGTA GACCTGAATT TAAATCCCCG TTCTGTCAGT TATAATGTGA CCCTAGACAA AACACATJ7CT CTGAACCTCA GAGAACATT1C 25 TTCA'IMGTA GAATGGGAAG ATTAATCTAT ATI7CCACTTG GATGGCAAGT CTITTATAAA CTTATAACC TAAACATGTG TGAGTTGCTA GTATCATTAT GTTGGTAAAG T-rAT7CTGAG ATATGATAAC AGAACTGTr TGTCTAACTC CACTAGCATG GTTCAGGT AGAGAGTGTG GAATIAAAAG GCTTTATCCT CAAATATGAC 'I1AAATCCGA TITICTCAT CCAC'TTCCT CCACAAACAA ATCCTCAGGA AATGACAAAC =TACATGGT TAAACATCAG rMT'TTAG TCTGACAT CCACATGG'IT AAATCATACA 3TTGAAAACT GCTTATATrT 30 GTGTTGTCTA TGTCTAAATT GAAAAGACI1' ATrTGAGGAAT AGAAGACTAC ACATITCA GCAAACACTG CACGTTGC AGAATTT1CCC CAGGCACCAG TCTCCAGGAA 'IMATTGGCT ACTAACAATA CTAAGATATG GATGAATGAG GAAATCAAAA TGGAGATCTT GCAAGTITG TGAGAATGGG TGAATGGTCC AAATGAAGAG ATAAGT'GTG AAATATTAGT ACAAGTAAAA AT~T ACA ATGAAAGACA 'YrrGTCAAT AGCTATGAGA ATTACCAT TGACCCAGAA ATrCCA'I=C TrCTrCAGA AATACCCACG TAGGTATACA TATAAAAAGT 35 TATrCATrAC AGTATCGT TTCATAGGAA AAAGTITIAA AAATCAGAAG CTATCTAAAC TATGGTATAT CTAGGTCATA GAAATCAAAT GACTAAAAAT GTTAATATAA GCATATG TrT TFAAA1TAAC TTGGCTTGGG TCTTCAGCAA AATGGC'rrC ITAACATT1GC ACTCCAGAGT TAGACTTACC CACTCAGTCA CTTATCATGC AGGAGGAGAC TCCTAATACC ACATATCATA GAGCAGAGTA GGACACAGGT TCTCTGCAGG CAGGCAAATC CCAAAGAGAA GGGAGGAAAG GGCTGAGACA CTGCATGGTC AATI17CTI1CT GAACTCTGCA ATGTACGGAG 40 GTGGACAGTG TCCACAAAGA TTGCTCCCCT GGACCCACCA TCATAATAAC ACAACGGCTT TG'FTrTT TTGTF1TGT TITTGACAC GGAGTITGC TCTTGTrGTC CAGGCTGGAG TGCAATGGTG TGATCTCGAC TCACCACAAC CTCCACYI7CC TGGGTTCAAG TGATTCTCCT GCCTCAGCCT CCTGAGTGGA TGGGATrACA GGCATGCACC ACCATGCCCA GCTAATI1G TATI=AGT AGAGACGAGG TI1CTCCACG 'TFGGCCAGGC TGGTCTCAAA CTCTTAACCT CAGGTGATCC ACCCGTC1G GCCTCCCAAA GTGCTGCGAT TACAGGTGTG 45 AGCCACCGCG CCCAGCCCAC AATGGC=1I TGTrACATC TCTAGTGCAG CACTCA ITC ATGTrCTrC AAGAAGAATA CATM1TCAT CTI=ATTr TATACAGCAA TTAGCACAGT GCCTGGCATA AGGAAAATGA TCATTAAAAG CTGGGTGAAA AACCTAATAA AGCTACTGAG GATAGGAACT GCAGACCAGC ATGGAAAGAA AACTATGAGC CAGATATTGA CATCATCCTG AAAGGCAGAA GATAGTAT AGGCAAGAAG TATGCFTTG GAATATAGAA AATCTGGATT ATGATAAGAA AAGAATCATA TIGTCTTAT CTTACCTACT CACTTCTCAG 50 TTCCACATGT TTCTGAGGCT GTI7rGTCCTT A=CTT'l CTGTM~ATC CACTCTTCT GTTCTTTAGA TTGGATCA IT CCTATTGAGC TGACATCAAG TTAACTGACC TTArT=G TCCAAACTGC TGTrAAATGC ATCCAGTGAA TTITAACT[ TATATAGTAT ATCTITAGT CCTAGAAYI1 CCACATGAGT YfTTAAG'T TCCATIT7CTC TGCTGAGATC TCCTATTTGT TCATTCATTA TGACCATATT YITCTCTACA TTATTGAGCA TAATT1ATAAC AGCTCTI7CTA AAATTCTTGT CTGCACATTC TAACACCTGA ATI7ATTCTGG GGTCAGTCTC 55 TGTTACATTG CCTTFACA AAAACAGTAT AAGTCACATT GCC TT C TTAATATGCA AAATGATTT TGATrGCAGA CTAGACA FI1' TGAA'ITAAAC ATTATAGAGA TTCTGGArrFC TCGAGAGAGT ATrGAC~rGT TTrCCATC AGGCAGGTAA CT7GACTGGA CTCAAACTCC AAACTCTAGG TCCTCTGTAA TGGGCAACTG CAGTAATCTT TGTTTAGTTC TTrAAGACTr AflGGCCAGG CACGGGGGCT CATGCCTGCA ATCCCAGCAC TGTGGGAGGC CAAGGTGGGA GGATCACCTG AGGTCAGGAG TT1CGAGACCA GCCTGGCCCA CATGGTGAAA 60 CCCTGCCTCT ACTAAAAATA CAAAAATTAG CCGGGTGTGG TGGTGGGCGC CTGTAGTCCC AGCTACTCAG AAGGCTAAGG CAGAAGAATC ACTrGAACCT GGAAGGCAGA GG'I7GCAGTG AGCCGAGATT GTGCCACTAT ACTCCAGCCT GGGTGACAAA AGCGAGACTC CCTCTCAAAA AAAAA M AT TGGCACTGCT TGGCATCTGC TATGAATACA TGAAGTTCAT GGGTCAGCTA TAGATCTGGG CACGTTATAC ACAGAAMIIG GGTCTCC=T TCTCTGGATT TCTCCTTJC TGGALTTC117 'ICTCATIT CCAGCAGCTG TGG'11GCCCT AAACTCGGTC 65 CTCTG=hCT TTACGGCAGT AAGA'IMGGG AACTTAGG 'TITACCTGC CTCTCAGACA AAATAAAAAA TAATITCAT CTTGATGCTA CTCC'TI7CT7 CCAGATGTAG ACACCTCTCT AA'ITTCCAGT TGVTITTAT TGCTCTCCAG AGTCTAAAGA TT1ATCATT1GT TTrCTGTGGG AGAGTTGGTC TGATAAAAAC TACTCCCCCA AAACTGGAAG CTGGAAGCTT GTAATTATGA ATAGAC'=G AGTAGTATTC TTCTIGGAA AAGGATMTA ACTACTCCCT ATGTACTTCT TTAT7CCTG TIT=CTCAT CCGTAATCT7 =rA=I~CA TACTTCCTAA 70 GTCAGACAAT TITCCTACTT GAAGATTCAG TGACTGCTAT CAAATGACCC CCATATTACT AAATACAATA TCCCCAACTG CATTATAAA AAGAAAMTT ACTGTrATr AGTAAACAAT GTI'GTAGAAT AGTAAAATAT TGCTGGGCTF TGGAGCCAGA TAATCAAGGT TAGAATCCCA GATTCTAACT TACTAGCTGG TGTATTAGTC C'TTCTCATG CTGCTAATAA AGACATACCC CAGACTGGGA GACTGGGTAA TIATGAAGA AAAGAGG'1T WO 00/62736 PCT/USOO/08020 195 AATTGACTCA CAGTCAGCA TGGCTGGGGA GGCGTrAGGA AACTTACAGT CATGGTGGCA GCAAGGAGAA GTTCCAAGCA AAGAGGGAAA AGCCCCTI7AT AAAACCATCT GATCTrATGA GAACTCACTC ACTATCACGA GAACAGCATG AGGGTAACTG CCCTCACGTT TAAT1rACC'Tr CCACCAGTrC CCCCCCATGA CACATGGGGA TTATGAAAGC TATAATI1CAA GATGAGA'IM GGGTGGAGAA ATAGCCAAAC CATATAAT17C CACCCCTGGC 5 CCCTCTCAAA TCTCATGTCC TCACATTCA AAACTCAATC ATGCCCTCCC AACTGTCCCC CAAGGTCT'FA ACTCATTCCA GCATI7AAGTC AAAAATCCAA GTTCAAAGTC TCATCTGAGA CAAGGCAAGT CCCTTCTGCC TATGAGCCTA TAAAATCAAA AGCATGTlAG TI'ACITCCTA GATACAGTGG GGGTACAGGC GTTGGGTAAA TACACTGA11T CCAAATGGGA GAAATrGCCA AAACAAAAGA GTTACAGACC CCATGCAAGT CCAAAACCCA ATAGGGCAGT CATTAACATT AAAGTTCCAA AATGATCTCC 'TTrGACTTCA TGTCTCACAT CCAGGTCACA 10 CTGATGCAAG AGGTGGGCTT CCAATGGCCT TGGGCAGCTC TGCCCCTGTG GC'TrGCAGG GTATAGCCTG CT'rCCTG1TT GC'TI=CAC AGGCTGACAT TGAGTGTCTG TGGC'IICC ATGAGTATGG TGCAAGCTGT TGGTGGAT-rT ACCATI7CTGG GGTCTGGGCC AGGTGCAGTG GCTCATGCCT GTAATCCCAG CACITFTGGGA GGCTGAGGTG GGGGATCACA AGGTCAGGAG ATCGAGACCA TCCTGGCTAA CACGGTAAAA CCCAGTCTCT GCTTFAAAAAA TACAAAAAAT TAGCCAGGCG TGGTGGTGGG TGCCTGTAGT CCCAGATACT TGGGAGGCTG 15 AGGCAGGAGA ATGGCGTGAA CCCAGGAGGT GGAGCTTGCA GCGAGCTGAG ATrGTGCCAC TGCACTCCAG CCTGGGCGAC AGAGCAAGAC TCCATCAAAA AAAAAAACAA AAAAACCAfl CTGGGGTCTG GAGAATGGTA GCCCTTrACAG CACCACCAGG CAGTGCCCCA GTGGGGACTC TGTGTGGGGG CTCTGACCCC ACATTTCCCT TCTGCACGGC CCTAGTAGAG GTTCTCCATG AGGGITCTAC CCCTGCAGCA AACYIFCTGCC TGGACATCCA GGCATI'CCA TACATCCTCG GAAATCTAAG CCGCGGAGGT TCCCAAACTT CAAT~CT7GA CTCCTGTGCA 20 CCCACAGGCT CAATACCACA TGTAAGCCAC CAATGCTTGG TCAGGGC'ITG AACCCTCTGA AGCAATGGCC TGAGCTGTAC GTTGACACCT 1TITAGCCTAG ACATCTAGGA CACAGGGCAC CATGACCCGA AGCTTCATAA AGTGGGAGGG CCTTGGGACT AGCTGAGGAA ACCATITT-C CATCCTAGGC CTCCAGGCCT GTGATGGGAA GGGCAGCCAT GAAGGTGCCT GACATGCCCT GGAGACGTIT TCCCCATTGT CTrGGTAACT AACATTCAGC TCCGTGTGCA GCACCAACTI' ACTI'ATGCAA A'TrCTGTCA CTGGTTTGAA TTTCTCCCCA GAAAACAGGA 25 TFrTCTr CTATT1GCATC ATCATGCTGC AAATITCAA ACTI=ATGC TATGCTTlCCT GTTGAAGACT TrGCGGC'A GAAATTTC'T CCCCCAGATA CCCAAAATTA TCTCTCTCAA GTTCAAAGrr CCACAGATAT CTAGGGGACA AAATGTTGCC AGTCTC1TG CATAGCAAGA GTGACCTTTA CTCCAGTTCC CAACAAGFT CTCATCTCCA TATGAGACCA TCTCAGC'IG GACTrAGTTG TCCATGTrAC TATCAACATT 'ITGGTCAAAG CCATTCAACA AGTCTCTATG AAGYTrCAAA CTfCCCCATG 'TITCCTGTC TCTAATAGC CCTCCAAATT 30 'TrCCAACCT CTGTCTGT[A CCCAGTTCTA AAGTCACITC TACATTTG GGTATCTTTA CAGCAGTGGC ACTCCCCATG GTACTAAIT ACTGTATTAG TCTGTI'CTCA TGCTGCTAAT AAAGACYI'AC TCGAGACTGG GTAAT117ATA AAGAACAGAG GTTCAACTGG CTCACAGTTC AGCATGGCTG GGAGGCCTCA GGAAACTTAC AAACATGGTG GCAGCAAAGA GAAGTTCCAA GCAAAGAGGG AAAAGCCCCT TATAAAACCA TCAGATCTTG TGAGAATTCA CTATCATGAA AATAGCATGA GGGTAACTGC CCCCATGArr AAMACCTC CCACAGGGTC 35 CCTCCCATGA CAGGTGGGGA TTATGGGAAC TAcAATrCAA GATGAGA'IM GGGTGGGGAC ACAGCCATAC CATGCCAGCT AGAGAGCCTI' AAGAAAGTCA CCTAATCTCC ACAAATAAAA GG'ITrCCTAT TTGTrCAACA AAAATAATGA CACCCCTIT ATGGGATrC TGTGAGGACA AATGATAACT AACATAGCCT TGCATAGTGT CTGGCACAAA ATAGCTACTC AAAAAATAAT AGAAACAACA TAAAAAAT GTAGACTTA 1TIT=AGAG TITATGTAC AAAGCAAAAT TGAGCAGAAT GTACAGAGAG TTTCCGTATA GCACTCCCTA CCCCCAAGCA 40 CAGATAGCCT CCCCCAGTAT CAGCATCCCG CACCAGAGTG GTACA'TrTAT TATAACTGAT GAATCTATAT TGACGTGTCA TT7CATCCA AAATCCATAG TTATAITAG GGATGCCTCT TGGTGT1'GTA CCTTCTATGG GT1TGACAA ATGTATAATG ACATGTATTC ACCATTACAG TATCATAAAG AATAGMTCA CTGTCCTAAA AATC'TrGAT CTI'C'TCCTA YI'CATCACTC CCTCCCCATT AATCCCTGAC AACTACTGCT AATITTCCTG TCTCCATTGT TTTGTC2Ff CCTGAATGTC ATATAGTA AATATACAGT ATGTAGGATTI TTCAAACTGG 45 TTTAT1V7CAC TAGTAATAT GCA LTTGATG TTCTTCCATA TC'TTTCAAA GCTTCATAGT TCAATATITA TAGAAT7GAA TAATATrCCA 'ITGTCTGGAT GTACTACAGT TTATGTATTC ATFCACCTAT CAAAGAACAC =TGGTTGCT TCCAAG'TTC AACAATCATG AGTAAAGCTG CTATAAACAT CTATGTACAT GTrTTGT GAATTGAACA TITCAGCTT YITAGCTCC ATI7CCTAGGA GTGCAATTGC TGGAITGTAT GATAAGGGTA TGITAGTGT TGTAAGAAAC TGCCACGCTC TTCCTAACTG GATGTACTGT ITGCATTCT CACCAGCAAT 50 GAAAGAGTTC CTGTTGCTCC ACATACTCAC CAGCATffGG TGTCGTCAAT GYITGAGCA ATAGCAYTT GATCTAAC' I TCCTAGGTA TTCIr=GA AGGAAATAAT ATGACAGATA ATAGAGAAAG GATATAGGAG GACAGTTCTG TCC'1TTATT ATAGTCCATC A'TTAATGAA GGACTCTGTC CACACT7GGT A'JTTAACT CTGATCCTCC TCTCCCATGA ACTCTGACAA TCTCCTAAAT CCCTGTT1GCT GGCACACATG GTTGTGTATC AGGCCCCCTG TGGTCTGTCT GAAGCATGGC YmTITITI TITI1rr=T fITIGAG ACGGAGTCTC 55 GCTCTGTCGC CCAGGCTGGA GTGCAGTGGC GCGATCTCGG CTCACTGCAA GCTCCGCCTC CCGGGTTCAC GCCATI7CTCC TGCCTCAGCC TCCCGAGTAG CTGGGACTAC AGGCGCCCGC CACCACGCCT GGCTAA'TI' T'FGTA TTTr AGTAGAGGCG GGG'ITTCACT GTGTTAGCCA GGATGGTCTC GATCTCCTGA CCTTGTGATC CGCCCGCCTC TGCCTCCCAA AGTGCTGGGA TTACAGGCGT GAGCCACCGC GCCCGGCCTT 'TTTT rT T~fT7T'T TTTGAGATGG AGTCTGTCAC TCTGTCACCC AGGCTGGTGC AGTGATGCAA TCFITGGCTCA 60 CTACAACCTC CATC'TrCAG GTTCAAGTGA TTCTGCCACC TCAGCCTCCC AAGTACCTGG GATTACAGGT GCCCGCCACC ACACCCAGCT MTTITGT AITI17AGTA GAGACGTAGT 'ITCACCATGT TGGCCAGGCT GGTCTCA17C CTGACC'1GA GTGATCCACC TGCCTTGGCC TCCCAAAGTG CTGGGAYITAC AGGCATGGGT CATCACATGT GGCCTGAAGC ATGACTGTTG C'ITTAATCAT ATGAAATACT GCTCTGTATT GTTATCTATr TGAAATGCCA CACCTCCTGA GCTAAA7rGC AAGCTITAT GGAGCACAAA CCATATITAT ATATAFTAGC 65 ATGATACCAT GACACATATC AAAAGCTGTT ATATATTGIT ACGTGAAITG ATCTTTCTC AGTrAAGAGG ACCTCTGTAG TAGCAC'TC ATACCGTI7AA TIT=CATm7 TGTGCCCAGC CCCTACTCTG TGAAAAATGA AATGAATCCT GTTATCAT CCCTCCCAGG CCTTCTCC TTGTGGACAA TGTGTGGCTC AAGAGAAAAT TCAGTCAGTA AATTTGTTCA GTGCACAAAC TC'TrATCAC CTCTCACTGT TCTCAAGTGA GATAGAACAG AACATCCATC CAGTGTCTrFA CAAA'ITGTCT GGTATATAGT AGGCACTCAA TAAATGTIT TTGAATAAAT 70 GCATACATGA ATCCTATTCC TATATATAGT ATGGTAGACA GATCATTGAT ACCCAAAGAT GCCCAAATGC TGATCCCCAG AACTTGTGAA TATG1TACAT 2FTCATGTCAA AAGGGAC'IT GCTAATGTGA 'FrAAGGATrC AGACCCTTrGG ATTGTAAGAT TATCCCGGAT TAACCAGGGC CAATCTAATC ACATGAGACC TTAAAAAAGC AGAAAACATT TCCCAGCTGG GTI'AGAGAGA GATGAGACAG AGTAAAAAGG AAAGAGAYI'C AGGGCATGAA WO 00/62736 PCT/USOO/08020 196 AATGACTCTA CCCACTGTTG CTGGCTGA AGATAGAGGA ACTAGGCCAC AAAACAAGGA GTATGAGTGG CCTTAAGAAA TAGGAAAAAG CCCTCATCTG ACAGCCAGCT AGAAAGCAGT CCTCTGACCA CAAGAAATTG GATT1CTGCCA ACCACTCAAA TGAGCAAGGA AATGGAT-FCT CCCCTAGAAC CTCCAGAAAG GAACACAGCT CTGTAATGCC TTGA=FTAG CCAGGTGAGA CCTGTTTCAG ACTITGACC TATGGAAATA TAAGATAATA 5 AAG'rITrATI' GTATGCTGCT AAAMGCGG TAGMrATTA CTGAAGCAAT GGAAAGCCAA TACAGACAGA ATATACAGAG AGAAAGAGAA TGAGTTCTT CCTGATAATI' TGTAAATATT TGGGTCTTCA CTGGACAAGC TTCACAGAGG ATTCACTGGT TCCCTAGCAA ACCAGCATGT CCAGTCCTGC AGCCTCCCTT TCTTAGGCCC AGCATATGTC AGCTGTGTGC ATAGAAAAAT CAAAGCAGGA CCCTGAGTAG T7GGAAAGAA AAGATGGTTG GAAATGGGTrr GCACTTCAAG TGAGGAAACA AGAGGTAGGA GACCGGCATC TCTTTCTCAT ATGTCCCAGG 10 CTGACTCTT1G TGAGTTGTTT TCCCTTGGAG GCTATCGATG ACAGTCACAG TAACCTGATG GAACCTGGAT CATGATGAAA GAAGTAAGTG TCAATGGCTC CGACTFCCAA GGACTCTGAT GTCCCACAGC ACTAGCTAAA CAAAGCCAGT TGGAAATGAG CTTAAATGGG GAKIT~CCTG AATATA'rTCC CTATTGTTAG GAAGCCAGGT TGGCTrCCTr GCCTACAA'I1 ATGCCAAGCA GTCACACTAT AGAGTCCCTA GGGACATGAT ATTAAGTGAT TCTITAACA CAAACAACFI' AATAATCAT1' TATACTAATA GCAAAACGGC CAACGGCTGA TATIfCCACTT 15 GAAGTAGAAT TGGCTATCCA ACTGGAAGAG AAGACAGGAA GACGTGATCT CCAGGGAGCC ACTAAAAGGA T'TGGCACCTG CCTCTGGATT CCCCI=fCC TTATATTACC TCTCAGCACT GGCAGGCCTr TATTTCAGGA TACAG=TCA CAAGTATTAT GTCACGTCTC TGAGAATTAT G'rrGGTAGAT AT'GCTCCT CTGGCCAGAA AGACCTAGTT TGGAGTCTGG AGTCATGAAG GTGACATACA TGTAGCTAGT GACATAAGTG TAGCTAGTAA AAATAGTGAG TAATGGCCCT GAAAT[CTAT TGAATGCCCA AAGTGCTGAC CAGGAACAAG CATGCTCTAG 20 CT17ATCTCAC AAGGAACYI'G ACAATITCT TCAAAAATCC TAGTAGCTAA GA'ITTCTTAG TAACAAAGCC ACTAAGGCAC AATTATGA F[ AACTTGACCC TTAGGTGACT TTAAGGACT ATTCTATAAA ATATTACAAC TAATAGTGGA TCCAAGCCAG CACACTCTGC TATATAAGAT TAAYFGACAG TGTCCACACT GGTAAAATAA GTTGTTTCAT AAATACAT[A GAATI7CA'IT GCACTICTA CACAGCCCCA AGTCCAGAAC ITICCCCAGA ATAGGTCTAT GYTFGCAAT CTGCTACTCC ATACAGAGAT TTGAGTTCAC TTGGCAAT AGTGCTGCTT 25 ATATGTGACC AGTTAGTCTG T1TACTTAT CTATGCC'ITA AACATTACTA TACT-TACTAA CTCCAAGATG CCTGGTCTCA ACTTGACAAA AATACCCCAA GTTGGGAAAT CCITATGTGA ATATGTAGAT AGTCACAAIT GCTGGTTGAT GATGATCTGT CITICCTGT ATTGAGAAA ATGGAGATAA AATGGACCAA TCCAAATAAT GGATI1AAACA TGGGAATAGG TGAGAGAGAG AGAGGAATAC ATGGTGGCTC TCAGTGTCTG GCTTAGGCAG TAAACAC'TT CGTTAATAAA GACGGAAAAT AAAAAAGGAA TAATTGGTGT CTAGGGGAAA ATAATGAGCT 30 CAAGTITTAA CACTCTGAGT TCCCGGATGT GAGACATCCA GGCGCATITA TCCAAGAGGC AGTrTGGAAGC AACGTTCCGG AGCITrAGGAG AGAGGCATGA CCAAAAGCTG GTGGGACTGT GAAAAGGTAT GGCCATTCTG GAAAACTGTT TGGCAG'TrC TTAGAAAATI' AAACATGTAC TAACAACCCA GCAATTGTAC TCYrGAGCAT TTGTCCCAGA TAAATGAAAA AAAAAAAAAG CA TT1T ACACAAAAAC ATATACATGA AAG'PTCATAG AAGTGTJ7ATT CATAAAAAAC TGGAAAAAAC TGAGATGTCT ITATI'GAGTG AATGCTTAGG CAAACGGTGG 35 TCTATCCATA CAATGGAATT ATGCTTAGCA ATAAAGAGAA AAGAACTATT GATACATGCA ATAACACAGA TGAATCTCAA AGGAATTIAAT GCTGAGTGGG AAAAAAAGCA CATCTCAAAA TGGTATATAC TGTACTA~rT TA=TACTrA ACAT=AAA AATAGCAAAA TCATAGAGAT GGAGAACAGA TTAATGGGTA CTGTGT = G GGATGGGGAG TGAGAAAAGG GTAAGGTGTA AATATAAAGG GGTAGCACAA AAGAGCCTTG TGGTTGAAGG ATTCTATGTC TTGG'ITGTAG TCGTGAL17GC AGGAATCTAC ATGTGATAAA ATI'GTATGGG TCTACATACG 40 CATACACACA AGAGCATATA AAACTGGTGA CATGTGAAGA AGCTCCGCAC A'ITGTGCCAA CATCAGTATC CTAGT7TTCAA TATCAGACTA CAGTTATACA AAACATrGTC ATTGAGGGAA ACTGGGTAAA GGGAACACAG GACAYITGGC ATATATT1T GCAA'T7CCT GTGAATCCGT AATTA ITTAA AAATAACAGA 'TATACTACAT ATCAAAAATT TAATGTCATA AAGT7GATGA GTJTACCTAG TGGATAGCTT TGTTAATATC TGCTATAAGA CTACTGAAAA TGACAGTTAT GCAAGTATAA GCTCAGAGAA C1TCCTCCC CCTrCGTAAA TGAAATGAGC 45 AAAAGAAATG AAACAGGAAA GGCAAGCAGT ACTGAAAACA GGGAAGGGCT CTTrCCCCATA TAACTATATC TGCGACT'FCA ACAGCTATTC ATCCAGAAAC ACAGCCTCT GCGCTAAGAG GAAACT1TGG ATAACAATAT GFT=CACTC TCCAAGAGAG AAAATGGATA GATrAATT TAAGAAAAAA AAAAAAACCT CACCAATC ATGCTGTGGC TTGCACCMI AATCCCAGCT ACCTACAAGG CTGAGGTGAG AGGCTTFACTT GAGCCCAGGA GTFrCAAGGCT GCAATGAGCT ATGATrGATr GTGCTATCGC ACTCCAACCT GGAGTACTAA GCTAAGAGCT 50 AAGAACACAG CTGAGAGCGG AGAAGAAACA AACAAATCTG ACCAATAACC CCCACTCCCC TCATPIACT GGAGTGAGCT GAGACTGCTG GCAAACATGG CCTTGACCT AGCCTGAACT GTAGCAAAAG TCATCAGATA T=CCACC AATCAACAGA CAGAAGTGGG GAGAAAACAA TCGTAGTTCA TAACTACAAC AAGCAGATAA ACGAAGGCCA TGGTGAGGGA TGGAAGACAT TGTGATATAT CAAAGGCAGG CTCATTTAAA ACTCAACCCA AATTCCAAAC AAAATATATA AT7GAATATG TATTAATGCC AAAGGAGCTT GAGTGAGCTT TAGCACAAAC 55 CCCGCCCTCC AGCCCCCACC CAAAAAAATC ACTCTG I17CT CTCCCCATT1C TITGATAGGC ATACYTGCTG 'TTTCTCACA GCCAAGGTAC AGAGGGGACT TAGAGGAACT AGAACTCTAA TACACTGCTA GCAGGAATGT AAAATGAAGC ATCTACTTCA GAAAACCATT TTATCAGTIT CTAGAAAGTT AAACATAGAC CCACCATGCA GCCCAGCCAC TCTACTCCTA AGTATrACA CAAGAGAAAT GAAAACGTGT CCCCACACAG PrGTATTTAA AGGTGATGGT TAGCCTrGTG TGTCAACTTG GCTAGGCTAT AATACCCAGT TACTGAATCA AATAGTAATC 60 TAGGTGCATC TGTGAAGGTA 'LTIGTAGAT GTGGTrAACA GCTACAATCT GTTGACTTCA AGTAAAGGAG ATTGCTCTTG ATAGTATGGG TGGGCTTFCAT CCAATCAATT GAAGGCCTrA AGAGCAAAAA GTAAGG'TrTC CCGGAGAGAA AGAAATTCTG CCTCAAGACT GCAGCCTCAA CTCCTGCCTG AGFV~rCCAGT CAGCCAGCCA GCCTAAAGAT TlGCTAGGCA TTATAATCAC ATCAGCTAAT TTCTTAAAAT AAACCTCT ATATATATTG ATACAATGAA TGGTTATAGC AGCCTI'ATTT GTAATAGCCA CAAACTGGAA ACAACCTAAA TGTCCTTCAA 65 TAAGTGAATA CATAAACAAA TTGTGGTATA TCCACAAT TTACGCAGCA GTAAAAAGGA ATAAATGGTT GAATAAGGAA TAAACACATA ACAAGGATGA ACCTTAAAAC CGTAAGGCTG AATGGAAAAA GTCAGACAAA ACTAATACAT ACTGAATAAT TCCATITATA TTGAAGTTCT AGAAAATGAG GACTAACCTA TAGTAACAAA AAGCAGAAAA ATPPGCCCA CTGGTGATGG AGGGGGCGCA GGTAT7GTAG AGTATCTGAG AAAGGACAAC TGGATAAAAG GGGGCACAAG AAAACrI=G AGGGTGATTG ATATGTTCAT TATCTTGTGG CATGGFTTCA 70 TAGGTGCATA CATATGTCAA AACATCAAGT TATACACTrT TAAAATGTTC AGTITTACTGT ATATCTATTA TACTI'CAGTA GAGAGGAAGG AAGAAAGTGG GCAGGGTGGG GGAGAGGAAA GGAAACGAGG GAGGAAAGGC CCTAATAGGA AGGATTTTGG AGTrAGATT 'PTAAAATGAT AAAGGATGTT TGACACTCTA GGCATATGAC GAATATAGGA ITrATGAGTCC ACAAAAACCA CCAGGAAGTC ATGTATGTI1 ATAC'IPAA GTGAAGGATC WO 00/62736 17PCT/USOO/08020 AGTGGATrAT CAACTCCCTA ATGCTTTGCC TCTCTATGAC TGGCTGCTGT CCTTCTCATC CCAATACTCC TTCCAAAGCC CCTTGC'TrAA ATGTAAGCCT TCTrrCCTCC TITCAACACA TCCTGCATT1C CGTGACAAAA TAAGY1TCC TTAAACAGAA TGTACAGCAT ATTATVTGTA CAATrAAAAA T=TGGCCA GGTGTGATGA CTCATGCCTG TAATCCCAGC AATTTGGGAG GCCGAGATGT GTGGATTACC TGAGGTCAGG AGTTCGAGAC 5 CAGCCTGGCC AACATGGTGA AACCCTGTCT CTACTAAAAA TACAAAAATT AGCTGAGTGT AGTGTGGCAG GTACCTGTAA TCCCAGCTAC TCAGGAAGCT GAGGCAGGAG AATCGCTTGA ACCTGGGAGG TGGAGGTTGC TGTGAGCAGA GATCAGACTA YrTGCATrCTA GGCTAGGAGA CAGAGTGAGA CTCGGTCCCC AAAAAAAAAC ACA'TT= TTAATGTTTC CTCCTTGCCT GTAGGAAAAA GGCTCTGACT CCTTAGCCTG GGCATCAGAG CTCTATCTAA ATGGACTITA ACCTGATTTr GTGGCACTAA TTCCA'FrGCA GTACTTGTCC GCTCACTGGC 10 CTGTGCCTCT CTGCCACTAT TfIGGAATA ATGTCCTCTC TCCATCTTGT TTACTCAACT ATATCCAACC TCTAAGGCTG TGCTCCTACA AAGCCTCCCC TGGCTACTTC AGCCCACAGA GATATTTAAC TGCTCTGCAG TI'CAGGACAT TC'FCTGACT C'IMAAATCA CA'ITTACTTA TATATGATCT TGTGATAMII ITTGTTGACG TGTI1rACTrr AATTTTCTTC CATAACCTAT TCATTCAACA AACTCAACAA T7ATTTATTA AATGCCAAGT TAGAAAAATA TrATI'GA'TF TATATAGATT ATAGATATGT TTGAAATM~ AITrGGCAAT CTGCAAGTAG 15 AAAAATAATT ATAATGTGGT ATATCTGTGA TAGAAGTATT1 AGTGCAGAGA CCATGGGGAA CATAATCCAG CCTGGAAGTT CAGGAGAGAT ACGTGGAAGA AAGGACGTCA GAGCCTr CCTACAGGCA TGGAAGAAAC ATTAAAAAAA A'T1rrTTT 11GAGATGGA GTCTCACTCT GTCTCCCAGC CTAGACTGTG GTGGTGCGAT CTCTGCTCAC TGCAACCTCT GTCTCCCGGG TTCAAGTGAT TCTCCTGCCT CAGC'ITCCCA AGTAGCTGGG ATTACAGGTA CCTGCCACAC ATGGATGATA AATATGATCA TA'T=1CTTG TTCYTrCCT CCTCAGT~rGT 20 CTTCCCTGAA GAAAGGAATG CCTTTTATAG ATGACAAACT CCCATTCTCA AGAACAAGGA ThITGACCA NVI1TAATTTA ATCAGATGTC TGGC1TGAC CTAGAAACAC AGTCACGAAA CTTGGTGATT AGAGACCAAT TCCCAAACAT GAGCATTTCT TAGGAAACAC AGTAAAGATC TGAGAGACCC AAGAGCAGAA GGGCGAGAAA CCAAAAGCCA TCAG'TTGCA TAGGAAACAC CTTrGrTAGC CTAATCTTTr TAT=TAT~r ACTCTATT AG TCACTACAAC TATITTTCTGA TTGCTATGGT GATAGATGGT TTAAAACAAG CCYI'CATTAA GAATTGTCAC 25 ACCATGGTCT CAGTCAAAAA CACCAACATT TITA'ITGGTA TTGACAATTA TGGGAATATC CAATI'CCAAG AAGACAAGGA GACCTCTGAA CTITCTAAAT GAAGACTCCA ATCTTCCTGA TCTGATGGGA AGCAGCTTGG CAAGATTJACC AACCACCACC ACAGAGAGTG GACTCTAAGC TAAGACTTFAA AAGATAAGTA GAAATTATCC AGGTAAAGAT GTGTACAGAG AAGGAAGTAC ATCCAGGGGA AAAGAACAAT ACGTGCAAAA GTACGGAAAT GGTAAAAAGT AATACTACAT AGTCAAAGCC AAGCAGAGTT CAGAAGGGAT CTGGTGGTGA AAAATACGGC 30 TAGAGAAAGC AGCAAGGA'IT GGCTTCTAAA ACCTATGTAG TATC'TrGGAC cTACCCTAA ATGTAATGAG AAGCTTCTAA AGAATCTTTC AITATTCAT TCATTGAACA AATATITIGA GGCTTTCTGT GAAGAACATC ATTCTAAGTA GTAAAGATAC AGCAGTGAAT AGGACACATA AAATCCTAGA TCTCACAGAA TTGACATITCC AGAGAGGGAA AGGTAGACAA TAAATACATA AACAAATCAT TI'AACAAGAT GA'ITTCAGAC AATGGTACGT ACTGTGAAAA AAATGAAACA AGGTAATGGA CAGCGAAAAG GCACTGGAAG GAAGCCTGCT TACC ITGCA 35 TGGTTAGAAA AGATCTCTCT AAGAAAGAGA CCACATGTGA GCTGCGACCT GAAGGATACC GAGAAGCTAG GTGTGCAAAG ATGTGGGGAC AGAACTITG GACTGAATAG CAAATACAAA TGCCCTTGGG TGCAAGCTTT GCCTGTYFCAA GGACCAAAAA GAAGGCCAGT GTGCCTGCAG CATACTAAGC ACAGAGGAAA ACACTG'rrAT ATGCTGAGAT TGGAATI'ATA AGTAGAGCCA GATAATATAG TCTCTTATAG GTCATAATAA GGCAACCAGA TITATTCCA AGAGGATrA AAAATCACTG GAGG'TI'GC ACTAGGGTGA GAGGTGTGAT TrrGTA'TTT 40 AAAAGATAAT TCTGGAGAAT TAACTATAAT GAGGTAGGAG TAAACTAAGT TAGGGGCTAT TTCAGTGGCT CAGACAAGAG ATAATGGTAG CTTAGACTAG GATAGTAGTC GTAGAAATAA ATAAAAGTGG CACTCTACTT TGGGGGTAGA GTCTATAATA GGTTTGG=V ATGGATCATA TATGAGAGTA AAAAAAAGAA AATAAATTAA TAATGGTTCC TAGGT11TGTA CCTGAGCAAC TGAATAAATG GGTGCTGTGA ATTGAGATAA AGGAGATTGA GAATCACAGG C'ITTGTE=G CAAATTAATT TTGAGAGGCT TAYrAGACAT CCCAGTGGAG ATITCAGGTG 45 AGTGGAGCCC ATTGAAAGGT AAGGGACAGG GTCAGGTGTG GTAGGTCAGG CCTGTGATCC CAGGACM~G GAAGGCCAAG GCAGACAGAT CAGY7GAGCT CAGGAGTTTG AGACCAGCCT GGGCAACATG GGAAAACCCT GTCTCTACAA AATATGCAAA ATATTACCTG GGCATGGTGG CATATGACTG TGGTCCAAGC CACYTGGGGG GCTGAGATGG GAGGATCACT TGAGTACAGG AGGCGGAGGT TGCAGTGAGC CAAGATCTCG CCACTGCAAA CCAGCTTAGG TGACAGAGTG AGAACCTGTC TCAATAAATA AATAAGAAAC GTAAGGGAAA AGGAAATTAA 50 TCTGATCATT GGCAAATGCA TAGTATTTAA AGCCAGGGGA GTAGATGAGA TACTCAAAGT AGGTGAAGAT AAGGAGGCAA TGAAGGCCTA GGACTCTGGT GTACATTTAG ATGGTTATAA GAGGAATAGA AACTGGCAAA ATAAGTAACA CTGAGCACCC AATGAGGTGG AGAGGAAAGC CAGGAGATGA AGCATCATAG AAGGCAAGAG AAGAAGGGTG TCAAAGAGGC GAGGCAGTCA TCAAC=CTG GGCAGTCAAA TAATATAAGG ACAGAAAAGT GACCA'ITGGA 1TTrGGAAATA TGATGAGCAC ThrGAGTGGA GTGTTGAGAC AGAAGACCAA TTAGAGTAGA 55 TTGAGGAGAT AACGAGAAAT GAGAAAATGT AACCTGCAAG CACAGACAAT TCTTGAGAGA CTITTCTGTG AAAGGAAACA GACACAGAGT C'ITAGCATGT CTTGTC1TTC TATGGGAAAT GTAAATAGTT1 TGAGATCAGG GATAGTATr TATTCTGCTT TTGTACCTC TACA'ITACCT AGCATAGAGC TAGCTAATGT GCACTTAAGT ATGTTCTCAA TTCTTATCGC CTGAATGACT GGATGGGTGA AAGAATGGAT GGATGGATGG ATGGATGGAT GGAAGGATGG ATGGATGGAT GGAAGACTI'C TGATTTGCCA AGAAGAGGAT ACTGGTAGCA GAAATAAAAA 60 CAGCACTGGA GAAAGAAGAG TTTAGA=II TATrC'ITGG TGTCAGTT1AG ACAGGAAAGT AAGACATTAG AAGAGTCCTT AGATAA=TA TGTAATrG'rr CAM'1AGGAT 'Tr17AAATGT GATCACTGAT ATTGGACATG TTCCTAGTGA AGCAT1TG GTGY=CACT GGTrGAAGTT AATAACTGTA AAATTATC CCGTrCAGGA CAGAAAAACA GAAAACTTGA AGCTCCTATT AGAAAGTrCA AGATTCTCTG GGG FICTrAG GATITACTGT TCCCAAAACT CTGTCAAGAA CAAGAAAATG ACCTGTATAC TTAACTGGTC TAGGCAACAG TGGAAAGACA 65 ATTCTCAGAG AAGATTTGTrT TAAGAAGAC AC ITCCATA GGAATCAAAC AATAGC1TC AGTGACTAAC ATGGTAAGAC ACAGGGTGTI' AGCTCTTTCC TT1CCAACCTC ATGGCTG'ITG TACC'TrACCT 'ITCGACCCCG TGTTCCTGAA ATrGTI'AAAT TCATAAAC'T ACCAAGGACT AACCAGCCTC TGGGGAAflG CTGTATACTr AGCAAACTI'A CAATGGACAT AITrATAAGC CATAATGATA ACTGACTAAT AGGAAATACC CTCAACTGAA AATGAGAGAT CATCATTTGC AAATGAGTIC CCTTGCCCAG GCAACTACTG GGGAAAATGT CATGCAAGCA 70 AAATTAATCT 'FrGAAATCCT CCTIICCAT TIT1GTGTC T7CCT=PCC ATAGGCACCA GAAATATCAT GGTGCCTGGA TCTCATCTCT ACAGAAAAAA AAAGTGA'TrTY GATAAACTGA 'ITTATA'FrGT GTCCAAATGT GATTGTNT TCAAAGATAA CCTAAGGGGA GAATGCTGTC TGGCCCAACA GCAGGCTCTC GACTTCATIT CAGACACTGT GGCCAATGGC TGGGAAACAG GTATGAACAG TAGGTTTCTG AGTCCCCTGG AATTA'rrCCA WO 00/62736 PCT/USOO/08020 198 TTTATGTAGC CACCTCCATG ACAGGAAGCC TCCCTACTCT TACTTCCCAG TrrGTTCATr CATGGCACCA GGYFGCAGAT TAAAATGC TCAGTGACCT TTTATCTAAT AATGTGTrAC CTTCTTCTCT TAAAAAGTAC AAGGGACAAA TGCTCATGGT ATAC'IrAG GAGATTGTGG CTCTCTATrA ACAGTATrA TTCAACAAAC ATI1TATTGAG CATI7ATATG TGCATCATGC TAGGGACTGG AACCTAGTAA GTGTAGCACA TATTA TFTCA 5 TTAATCCTC ACAACAAACC CATGAGGTTG G'1IATGAT CCCAA T1T CAGAAGAAGA AACTGATATT CAGAACCAGT TAACTAACTG GTI'CAAGGTC ATGCAATC TAAGATACAG AACCAAGAGT CAAAGACATG ATITAAACC AAAGCYITTT CTGCTACTCC ACATTGCTTC CCTAGGTGAG ATCTGAGGCA I17CCGCGAAA AGAGAAGGGT CATAAAGCCA AGGGAAGACA AGCTTAGGAA AAAAAAGGGA AATGTCCTAA ATAAACAGCT TTCCTATTrA CCAGAAACCA CTAGTAAA AATATAATGG GAAAAATCCT ATrCACTrA ACAATGT7AA 10 AAAAAAAAAA GATAGAAGAA ACATAGGGAT AAACTAACA CA'TrGTAGG ATATGTAAAG AAACTAAAAG ATGTTAATAA TGGCCTAAAG AAAAAAAAAC I1ACATGTAT GGGGAGATAG ACCATCT7AC TGGATTCTAA TATTTAATAG TCTAGGTGTI' CCATITCTCA CCAAATTAAT GTATACAT AATACAATGT CAAACGAAAT ATCTTAGGAA TI'GCTTACAA ATTGTCAGAT AA2ITACAAAG TACCTGGG AAATATAAGC ATATATGAAG AGTGAATGGG ACCCCACCAC TCCCCCCAAA ACAAAAAAGG TCTGAAAAGG ACAGAAATCA AGGAGAGTCT 15 TGCCTGCCAG ATACAAAATT CTATTATAAA GGTGTATTGA TGAAAACAAT ITAATACTAG TGTAGCAATA GGCAGCAAAG CAATGAAACA GCATAAAAAG ACCAGAACTA TACCTAATFTA TGATGAAGAT TTAAGGTATG ATAAACATGA CATAAYrCAA ATCAGCAGAA ATTGGCATAG ATAGGGTTAA GACAAATAGC TAATCATITAG AGGGGAGGAA GGAAAGGAGG GAGGATAAAA TFAGGTTCCT GCC=CATCT TACATTAAAA TAAATTCCAG ATGTA'rTACA =~AAATT TAAAAAAA GAAACCACAA AATACTrGAA GAAAATATAA GTTGrITATAT 20 AGTC TITGA TGGGAATT TT YTTTC AGAGACAGGG TCTTGCTCTG TCACCTAGCC TAGAGTGCAA TGGCATGATC ATGGCTCACT GCAGCCTTGA ACTCCTGGGC TCAAGTGATC CTCCCAGCTC AGCCCCCCAG GTAGCAGGAA CTACAGGCAT GCGACACCCC ATCCAACTTA TTI=1A=f TPGTAGAGA CAGGGGTCTI' GCTTG'rTC CCAGGCTTAT CTCGAACTTC TGCCTTCAAG CACCTCAGCC TCCCAAAGAG CTGGGCTGAT GGGACATMT T~rAACATAGT GCCACATTAC CATAAATGAA AAGCTTGTAA AATACTAAT TrAAAACTA 25 ATATATATCA GAAAITTTA TAAACAAAGT TAAAAAGCAA ACACAAAAAA 'ITTGTAGCAC 'rrATGACAAA TATATGTATA TATATGAATA CAAAAAGAGC CT=ACAAAA CAGTAAGAAA ACAATGAATA CTCCCAATGG AGTATTCAAA ACTAAACTGC TAAAAGCAAT TCAAAACAAA AAACATAAAC TATGCATATA TGTATGTGAA AAAGTTTAAC CTATCAAAG AAGTAAACTC TCAAAGAAAT AAACATCAAA TAAGGAAATA GCCTITCCC ACAAATAACC AAAATCTGTA AGAATACTGA GCTGCGAATG 'ITCAGAAAA AAAAAAAAAT CATACACCTA 30 GTTCGGCATG TAATTAATAT AGATCAGAAC AC'=AAAAA TATTTATAGG CCAGGCACGG TGGCTCATGC CTATAATCCC AGCACTTTGG GAGGCCAAGG CGGGTGGATC ACCTGAAGTC AGGAGTTTGA GACCATCCTG ACCAACATGG TGAAACCCTG TCTCTACTAA AAATACAAAA ACTAGCCAGG CATGYTGGCG TATGCTGGTA ATCCTGGCTA CTCGGGAGGC TGAGGCAGGA GAATrGCTTG AACCCAGGAG GTGGAGGTTG CAGTGAGCTG ACATTGTGCC ACTGTACTCC AGCCTGGGCA ACAAGAGCAA AACTCTGTCT CAAAAAATAA TAATAAATAA 35 AAATAAAATA =TATATACT CTGACCCATC AATIGTCCA GCATAATrAG GCATGTGTAC AAGGGFTTAC ACACAAGAAT GCCTATTGCA ATATI'GCTT TAATGCTAAA AAAAATTGGG GAAAATGCT-F TAAAAATATA GATTAAGACT GTACATTGTG GTACAGTCAT ATAATCAATA GTATACAGCT A'rrATTrATTr TTCAGCCACT GTCCAAAATA TAGCCTGGCC TAACAACATT CTGTTAGGAT ACGCAAGCAC CGTGAGGAGA TCAGCTATAA AGTATCAGTG 'TrTCACACCA CTGCTCC'JT GCTAATAACC TTCAATGGCT TITAAAGAAG TAAAAAACAA 40 AGGCAAAATT CCTTAGTCAG CCCTTAAGAC TCTCTGTrAC TTAGCTCAAA CTACCCT1T CAACAACACT GCCCTAACCA GGATGAG'ITT 'ITTGCCCCCC TGGAGTACAT TCAGCC'1TC CTTATCAAAC CTTCCTTTAA ATAAGTATCT TCTCCAGGAC CACTTCACTT TCTTCCCCAA TTAGCATI17 TCTATATCTC CAGGCCTACC TCTATAAAGC CTGTCCTAAC CACTCAAACC CTAGCT11T CTCTGAACTG CTAGAAATAT TTTTCTCTCA TFrGGCCAT AGGTAAAAAG GT11TACTG TTTATTACCT ACTCAATAAA AAT1TCT TTGAGACA 45 AGGTCTTACT CTGTCGCCTA GAATGGGGGG AAGTGGTGTG ATCACAACTC ACTGCAGC'IT CTACCTCCCA GCTCAACAGT CCTCCCACCT CAGCCTAGTG AGTAGCTGTG ACTACAGGCA TGTGCCACCA TACCCCACTA CTITI'CAIT TTTATTrr= GTGAGATGGA ATCTCACTAT GTTACCCAGG CTGGTCTGCT GATCTCAATT GATCCTCCCA CTGTGGCCTC CCAAAATGCT GGGATI7ACAG GCATGAGCCA CAATATCTGG CCCCAGTAAG CT1TAAGGC CATTAACATG AGGAACAGTG TrC'ITrACAC TATI=ATCA GCTAGGGCTFI TGCATGGAGT 50 AGGAGTIAG TAAATGCGGT TGATGGGTFA ATCAATGTGT GAAAATATTC AGAGCCACCA AAAACAGATA T'ATGTCTAT TCTCATCAAC AATCAAAATT GAGTAAACAG CCATITCTA ATACAGGAAA CCACAAAACA TTGAATGGTG ACATTAAAAA ATTCCCCCAG CAGGAGCCAA CCAATTT CATCCTGATC CAAGTTAGCA AACTGCAAAA GATAGGAAGC ACTAATGAGT GGAAATGA GTAGAAGCAT TTCTTATGAA GGCTGTCTTG ACTGGATCAC A'TITATTG CTGTTGGAGG TGCCAAATGT GTGTGTI'TAT GCTAATCCTC CACCTCAGGC 55 AACACACAGT CAAGGATCCT ACCAAGTGTT ACCGTCAAGT GTCTGTT1GGC AGCTCAAGGC CCCAGCGTrG TTCCC'ITGCA CTAGGGAAAA GACATATT1CC AGGTACAAGT ACTCCCACTT TGATGCTACA GAGGAGTTGC TGAAC'TrGT GTCATTAATC TCTCTrCGTT AGATCCCAAC CCTGTAAA TCCCACTATC TGCCTACTCT GGGTCTTCAC CAATTTACTA GATCATAGTT GGAGAAAATC TACAAAGCCT TGCTCCC'= AGATrAAAC AGGTCTCCGT TT1AAA'ITTAG AATTGCTAAC I17CAAGCGGG CCCTrATGCG ACAGTATGCC TGTCAGTCAT 60 ACTACATIC CTCAATTCCA TTCATGTGAC TGCTCCATAC CCrTCCCTCT CTCTTCATAC TACTATTATC TCT-rCCCCCC TCCCTCATFI' TTAACTGATG ATCTTGTTTC CTA'TTCTCT GAGAAAATAG AAGCCATCAA AAGAGAGT CCACAAACTC CTACTGCCTT ATCTAGCCCT GTACCATATA CTTTGCAT~rT CCTCTCATTA CCATGGATGT ACTGCCTATC TGTGCTTCTA TCTAAGGCTA ACCC FTCCAC TTCAGTIT7G AATATTATCA GCTCYJ7ACCA ACTCAAGGCC ATTGCTCTAG CAATTCTCTC A FTCTCTCTC ATTFCl7CC ATCAAGTITT 65 CC'TITTCTTC AAT7AACAGA GTAGCTCCTA AAGGGAAAAA AAAGTC'ITCT TI=CAATGC TCATCATCAC TGGCCATCAG AGAAATGCAA ATCAAAACCA CAATGAGATA TCATCTCACA CCAG ITAGAA TGGCAATCAT TAAAAAGTCA GGAAACAACA GGTGCTGGAG AGGATGTGGA GAAATAGGAA CAC=PACA CTGTTGGTGG GACTGTAAAC TAGTTCAACC ATrGTGGAAG ACAGTGTGGC GA FrCCTCAG GGATCTAGAA TTAGAAATAC CAn7?GACCC AGCCATCCCA TrACTGGGTA TATACCCAAA GGATrATAAA CAATGCTGCT ATAAAGACAC 70 ATGCACACGT ATGTfI7ATTG TGGCACTACT CACAATAGCA AAGACTTGGA ACCAACCCAA ACGTCCAACA ATGATAGACT GGATTAAGAA AATGTGGCAC ATATACACCA TGGAATACTA TGCAGCCATA AAAAATGATG AGTTCATGTC CTTTGTAGGG ACATGGAGGA AGCTGGAAAC CATCACTCTC AGCAAACTAT CACAAGGACA AAAAACCAAA CACTGCATGT TCTCACTCAT AGGTGGGAAT TGAACAATGA GAACACTTGG ACACAGGAAG WO 00/62736 PCT/USOO/08020 199 GGGAACATCA CCCACTGGGG CCTGTTGTGG GATGAGGGGA GTGGGGAGGG ATAGCA'ITAG GAGATATACC TAATG'rrAAA TGATGAGTTA ATGGGTGCAG CACACCAACA TAGCACATGT ATACATATGT AACAAACCTG CACGTrGTGC ACATGTACCC TAAAACTrTAA AGTATAATAA AAAAATATAT ATATATATAT AAAACAACTA AAAATAAATC TrCITITICT GCAGGATCAG TCCATCACCA CACACACAGG CTGTGT'TJA TGTTGTTCCC 5 CAGCTTAAGA GATCGTTCTC CAGATCCCAC TGCTCCTTCC AGTFGTCACC TCAGTI7CTCC ACTrCTVTT7 GCTGATAAAC TACTCTAACT AGTrfACATAT GATIrTCTGTC CCCAGGTCCC CTCCCTCAGT TGT'TTFGAAC ATAATCA=P ATATCATITA TCMTPCAC TCTAATTGCA CAACCAAAAA CTCCCTITI TTITAGATGG AGTCTCACTC TGTCACCTAG GCTGGAGTGC AGTGGCATGA TCTCGGCTCA CTCCAACCTC CGCCTCACGG G'TTCAAGTGA TCCCCCTGCC TITAGCCTCCT GAATAGCTGG GAYFATACAC ATGCACCACC ACACCTGGCT 10 AATTGCTTTG 'TrGTTTG TGTGTGTGTG TG'TTTT 'TT GGA CAGAGTCTCA CTCTGTTGCC CAGGCTAGAC TGCAGTGGCA TGATCTCAGC TCACTGCAAC CTCCACCTCC TGGGTFCAAG CGATTCTCCT GCCTCAGCCT CCCGAGTAGC TGGGACTACA GGCATGCACC ACCATGCCAG GCTAATITE TrGTATTTTC AGTAGAGACC AGGTCACC ATGTTGGTCA GGCTGGTCTT GAACTCCTGA CCTCAAATGA TCTGCGCACC TGGACCTCCC AAAGTGCTGG GATI'ACAGAC TTGAGCTACT GCGCCGGGCT A IT=GTGTT TrTrAGTAAAG 15 ACGGGGFFTC ACCATGT7GT CCAGGCTGGT CTCAAACTCC TGACCTCAAG TGATCCGCTC GCCTCAGGCC CTCAAAGTGC TGGGA'ITACA GGAGTGAGCC ACCATGCCTG GCCATAAAAC TGCCCTTTFGT TAATATGACT GTT1GGCCTGC ACATT1GTCAA ATCCAGTGGC ATI7CATCTTA CTCGGCCAAC CTACGGCATT TGACACTGTC TGTC'ITTCCT TCTGTTCCTC TATCTG FITC CAGTATACTG GCCTGGC'IM CTITTrACCT CFITTATATG CTCT7CCAGT CTCAGGCTCC 'TTGGGGATT TGAAGGTATG T7GCA'IIG CTATTCAATG AATAATGACA 20 AGTAATGATC ACTTAAGACA TTAAGTGGTC AGTTCCT=A CTAGGATAAA AATAATTC TTCCCAACAT GGGGCATATT CCATTTCCAG TCTGACTGTT CTGTGTAATC =IGTATrCC TrGGCAGCCC C'TTATATC AGrrCATCTA CTGTGCAGGA AATrGGACAA ACA'TrGCAC TGGTATAACC AAATACAGTT GAACTTTGG CTrGACTCTT AGCTGAACTC ACCAAAAATA MTTTCTGTAA GAGACTGAGA CGTCTACGAG TAGGTT~C AGAATTAGTA AACATAAATC AAGGATACAC AGGTAGATTT GAAT7CAGA TAAACAACAA ATACTTT 25 AGTATGTCTA CTGAAATATT TGTATCTTAT CTGGCAATTC TACCTGGTAC AGAACTAATC CATTCTCTTG AAAGATCTTG ACTCTGTAAT AAG'ITC3TIG GTGATGGAAG GGAGGTAT CTGTAATTAG AGTCACTGTC TTCCTCCCAG TTTTTATCC TGGCCCAGAT CTGCAATGAA CACACGACAG AATCCAGGGG GGATGAAGAT GGGTGC'ITTG CAGGAAAAAA AAATT1AAAAA CATCTGAAAA AGCT1TGTA CTAAAAGAAT GTGATCTAAA AAAGAAAGCA GGAGAACTI' CTGTCTGCAC TTTACATCAG AACAACCTJG GCGTCTAGAA GCTGTGCCCT 30 GTGGGAAGTG GTGGTGCTTG GTAAGAGATG CCAGGACCAG TGGTACCCAC TGGGAGCACT GCCAATACCC AGCAAGGAGC ATGGGTGCAC AGTAAGGCAT TGCACTGTGA TI7CAGCATAA AATAACAATA AGGGAACGTC ACGGAGAAAA GGCCAGACTI' CC=rGrTA GAATGTGGGA AATGTCTrCT GAAAAATGGT AGTAAAAAAG CATGCTTGGA TGGTCCACTC CAGGCAAAAC TGACTAATCG GGGGTCAGGG ATACAACCCC TGCATCATAT G=~G=~CT GTT1GGGCTGA CATGAGGTTC ACTGTGACCA CTGTGGTTTA ACCCCATAGT CTCCTGGAAA 35 TACAGCCAGG TCAAGAGAGC TCCACATAAA ACATAATCAA AAAAATAAAC TCAAGT[CC ACTGATCAGC 'TTCACAAC TCTJ7ATCCTT TCACTAACTT TGGAGCAAGA 'TI'GAGAATF GGATGGCTAT TTGAGGGCTA TTTCTGCGCT TrAGTTCAAT G1TFCT TTC'ITrA GAGAACTATG GTTTTTTArr ATAiTTACAC Th'rAAGTrCT AGGGTACATG TGCACAACGT GCAGAITTGT TACACAGGTA TAAATGTGCC ATGTTGGTIT GCTGCACCCA TCAACTCGTC A1TACA'rrA GGTATrCTC CTAATGCTAT CCCTCCCCCA GTCCCCCACC 40 CCCCGACAGG CCCTGGTGTG TGATGT7CCC CTTCCTGTGT CCAAGTGTTrC TGITTATGTG ATAGATI7ACG TTTATTGATT TGTGTATGTT GAACCAGCCT TGCATCACAG TCACTTGCTT ACAAGAAACA AACACTTCAC AGATGGATCA TTATGTGTGA TAAGTGAAAT CCAAGGATTT ATGCTCAGAG GTGGGCTlrAA CAGGTAGGAA GAGCAGTATT 'I7CCTI7CAAC CATGAGTGTA TGCAGGTIT TC11TC'TT TGAGATGG AGTCTCACTC TITACCCAG GCTGGCGCGC AGTGGTGCGA TCTTGGCTCA CTGTAACCTC TGCCACCTGG G ITCAAGCAA 45 TrCTCCTGCC TCAGCCTCCC AAGTGGCTGG GATTACAGGC ACCTGCCACT GTCTCCGGCT AATITGTC TrT=AGTAG AGATGGGGT17 TCACCATCTT GGCCAGCCT GTCTTGAACT CCTGACCTCA TGAATCATCC TTCTCAGCCT CCCAAAGTGC TGGGATTACA GGCATGAGCC ACTGCGCCCA GCCCACAGGT YTrCAAAGA CTAAACTTAA AAAAAAAAAA AAAMTTTCCC AATGAAATAT AAAACTAAAG TGCTAAACTG TGATAGACTG TIT'ACAAGA ATGCCAGMII TCACAAGTGT CTATAGAACA TGTAAKIAG ATAGGTAAGA TGAAAT1TTG 50 ATAATA'TTG ATGGCAAA'JT TAAACAGGTA TACAACAAAA ATAAAATTCT AAGCCCCTCA ACCAACTGAA TGGACTCCTI' CTCTCAGCCA AAGGAATACC AAAGTAAACC TGAAAAACTA GTITGGCCA GGArrGGGGG TAGGTGGGGG AAGCCCAACA TGACTCA'ITA TTCTCTCCTC CCMTGGAAT TCAGGCACAA CTGAATGTCA GCATTGACAC TAAAACACAG ATCTT1AAGAC TGACAAGCCA GACTCTITGT AGCAGAGAGC CAGGCCCTGG AAGAAATCAA GTI'ATITTAT CCCAAAAAAT AMTCTT1GA TATATITCA AATGGCCCTG CAAAGCTGTC 55 TCTTGTGGGG AAAATTGACA TGCTGTACAG AATITCC1TC TC'TTrCCAAG 1TITACTGA TCCAGGAGAG A'TTAACTAA GAGGCTAGCA TGTTITIT TITTTT TGAGGCGGAG TCTTGCTCTG TI7GCCCAGGC TGGAGTGCAG TGGCGTGATC TCAGCTCACT GCAACCTTCG CCTCCCGGGT TCAAGCGATT CTCCTGCCTC AGCTTCCCGA GTAGCTGGGA TTACAGATCC ATGCCACTAT GCCCAGCTAA 'rITTrGTA~r 'ITTGTAGAG ACAGGG'ITTC ACCATGTTGG CCAGGCTAGT A L1GAACTCC TGACCTCGTG ATCCGCCCAC CTCGGCCTCC 60 CAAAGTGCTG GCATTACAGG CGTGAGCCAC CGTGCCCAGC ACAAGACATT TACCGTCTAT TCTCTCTGAA GCTACTATCT AGAGGCTI1CA TCAACATAAT AAGACCC'ITG GTCTCCACAA CTCCTTATCT TATCCTATTA G'1TTCTACTG AUTCCAGGTC TTTAGATAAT AACAACTC'IT TCAACCAATT GCCAATCAGA AAGTCTTrGA ATCCACCTAT GACTTAAAAG CCCCACTCCT TCAAGTTATC CCGCC'TrTCT GGACTGAACC AATGTACACC TTATATGTGT TGATGGATAT CTGCCTGTAA CTTCCATTCC CCTAAAATGT ATAACATCAA GCTGTAACCC 65 AACCACCT11G GGCACATGTT TTCAGGAACT CATGAGACTG TGTTGCAGAC CTTGGTCACT CATATFGGC TCACAGTAAA CTI'C'TTTAAA TA1TGTATAG AGTrGGCTT T=CATTGA CACAGGAAAA ATAAAGAAT7 GGAAGGTCTr TCATCAGTCA CTGAGCCAGC TT1CATATCTG ACTGAGGTCA TACAGTTCAG TGATTTGTAG C'TIGCTACT TAGATTGCTA TCCA'rrATCT AGAAGCATCA GGATCACGTG GGACCTA17G GAAATGCAGA CT=CCTCCT AGAACCCAGG ACC'ITGGAAT ATTCTTGGCA CATAGTAGGT GCTCAATACA TATI7GAACTC 70 CTAGGTGCAA T-rCATTAATr CATGAATTIAA TGAATTAACA CGCTCTCAAA G=IIAGTGCT PT=CACAGA CTAGTC'rTC TGCCTCTTAA GCACTCAGCT CACCACGCTT CCAGTCTCAC TCCCCTATITA GTCTGATTAA AATCTGCT'rA CATGTGAGTC TGAGATCAAG TGTTATCTCT TCTGAGAAGT CT31CCCTCAC TGGCCCAAAG GAMTTCTCC TCTATLfAG CACTGTCCCA GTTGAC2TTGT CA'ITATTCTA GTCTTCA TATTAG FTGT WO 00/62736 20PCT/USOO/08020 TITTCATATA TATGTTATT1A AGGAAACTAG TCAITrCCCC TAATAGAACA AAATTGCTGG CCTTTGGGGT TGGCAATGGA GGGGAGGCTC TT=GAAAA GGGGGAAGAG TGTJ7CTCCTA ATATTT7CT TACGAGA'TTT ATGTTGCTCA TCTIAGCCT TTAGTCCCCC ATTGCCTGCC TACAGTFGGC AGAGACCATC TGTrCTCTCA CTGTCAGGAA CTGTCTCAAT TCTTGAAGTF CAGAGTCAAA AAAGAAGCAA GTITTCCTAG CTCTPTGATC 5 AACn7~CAAA GTTTTACTC CATGAAAA TTACTAAGT CACCAGGAGA TGGTrTATAC TGAGAAATAT CCACTCATAC TCTrCCTC'f CAAC'IMCTT CCATATACAC CCTATTACAG GGATATAGTC TTrACTCTATA GCTCAAAAGG ATGACCCTAT CAGAAACCTG CACAGTATGT AAAACATTCT CACCAGAGGT TCACTrGTGT ATrTCCACCC TAGAATGGAA GCTCTACAAA AGCACAGAAT GTATCAT=T AACTTTAGAT TCTATFCA CACCCAGTGC 'ITGACACATG ATTGAAGTT AATATI1?ATT TATCAAGTGA VTGTTAAA ATCATGACTC 10 ACTCAACAAA GTTATAAGAA TAAGAATAGT G'TrACAGAAT TGGTATACAC AAGCTGACCA TAATCAACAC ACCTATTATC ATTTJGC GACAGGTTCT CGCTGTCTCA CCCTGGCTGG AGTGGAGTGG CATGACCACG GTTCACTGCA GGITGAACT TCCAGGCTCA AGCAATCCTC CCACCTCAGC CTCCCACATA GCTGAGCCCA CAGGTGTGTG CCACCATGTC CAGCTAACTT TTTAATTCTT TGTAGAGACA GGGTCACCCT ATGTTGCCCA AGCTGGTCTT1 GAACTCCTrG GCTAGAGAGA TCCTCCCTCC AAGGTCCCCC AAAATGCTGG GATCTCAGGC 15 AAGAGCCACC ATGCCTGGCC ATAATCAATA CAC'IIAAG AATGCTAGAA TGTATATCA GATGCATACT TCAGCACTAT CTCAAGCAAA CTGGGGTGTG GGTrATTCTA CATATAAAGT TCAGCAGTGT TGTTCCACAG TCCCAAACTC CAACTGAGGT CAAATGTAGG GTGCAGCAAG GTCACTGGGG CTGTCATCAA GGGCCTCTCC TTGCACTCT'T GCCAACCCTG TCTGATI7 GTCTCTACCA CCATGAGTCA CCAGCAATCT CCCACAGTCA CTTG=~AAA AGrrCACAAG TAT1'GTGTGA ATrGCAGGCA ACCC=TGAC TCCCTGATTG CCTGGTCTTC 20 TTCCTTGGGC TCTACCATfI' TITTCCCCA GCACTCTrC TGCTGCTCTA AATInrAA'I1 CATGCAATTC CATATGTGTT TCTCTATCAT TCTTCATCTC TTTCCTCTCC CT~rCCATCCA ATrFGITG TCTGTITGCT TGC'FrGCTTG CTTTAATACA TTTCTCTT TCTGAGAAGG C'IGAGTCCA AAACTCTCAG TTACCTGT11G TI'CTG=flCC CG'rrAGTrAA TCTCCGAACC TTCATAAATF AAATCTGACA AAGTCCCCTG ACTAACAAAG GAAATGCACA AGTCACAGTA AAAGGGGCAC ACACAGAACA CAAATAGACC CAGGGTCTI TCTG'ITCATC 25 ACTCAGC= TTATAGGAGA TCCAGGAGAA ATGAAGTGGA AAGGGAAGTG TGTFTGAGTFA CTATACAACA CAAGAGTAAA C'ITCTrATA AGTGGTAAT' 'TTTACA GGAATAATTG AAAATGGAAA TTACCTTCTC TACTCATAGT AAGTACTCAG TGCGTrCTTG ATGGGATGAG AATGTGTrTG AGCTr7AGTG TAAGGCAGAA TTCTGTT'rAG TCTGCCAGTA TTGGAGAAAA ATAAAACACA AAGGGACTGA CATGTAGGAA GTGGCACCTG GGAGGGTCTC AA ITCTTCCT ATTACAAAAA TGCCCCAGAG AAATAAAAAG CTTGTGTACA TGTTGAGATG 30 GGAGAG'ITCT CTGGCCCCCC TCGCAGGATG TGTGACAGTG GGGTGGCTCT CTGCTGCGCC ACCATGAGCT CAAACCCCTC ATAGGAGGGG GAGCACACAG GCAGGAAGGT GCAGGAGCTG GGCGAGCTCT TTGGGCTCTG GCCCCGTGGT ACTGTCTAGA GGTGGGTGCC TGCAACTCCT GAAAGCCCAA GTGGGCATGT GTI7ACAGTGC ACTCTICAG C'ITTGCTGTC TGCAGCTTAA GCGTTAACCA GCTCAGT1TC TTC'rTGGTAC CCAGGTCCTT GTCTGGCATC CAGGAAGAAT CAGGTrACAC ATGGACrTGA AGGATGAATG TGGGAGTTT ATGGAGTGGT 35 GGAGGTGGCT CTCAGTGGGA TGGATGGGGA GCTGGAAGGG GGATGGAGTG GGAAGATGAT ATrCTCCTGG AG'ITTGGCTG TCCAGCAGCC GATCTCCTCT CCAGTCGTCC CCAGCCTCTC GACGTTICAGA TGCTCCTCT7 CTCTCC=CT CTGCCATGCT GTFCTGCCGT TCATCTGCCT GTCTCTCTCT GGAGCCTGGA A'ITGGGGTT TATATGGTAC ACAATAAGGG GCATGGCAGG CCAAAAGGGA AC TTrAGG TGCAAAAAAC AGGAATGCCT CTCTCACTT AGGGCTATAG ATn7~CAGGC TTGAAGGTGG GGCC'IMACC AGCGAACCTG TA'ITTCCCTG 40 TCTCCTGTGC ATATCAATGT AATCAAATAC TGGGCTGATC CAGGATG'TrT C'TrAGACCA ATTATGGGTA AAATAA1TT'A CATTCAGGTT MIATA=JG C'TPTGTCAT TTFrTITAA GCAATCATGT AAAATATCTA TACGACAGTA ATAGATGATA GCGAACCTAA TTAAAAYJ7AC CAGAAACI17A AGAATCTCTA ATGA'TrTCAA CTGTAACTAA GG FTATCT CMTATGTTG AACAATGTTG GGAGATAAGA CACAAGAGTT TCTGAAGTAT TTCAGAAACA CAAAGAGGGA GGTTATATAA ATAATATIT 'TCCTA=r TGGGAAAATG AAAGCTAGTC 45 ACAAAGTTAA ACGAGTGGTT1 A=~AATAT TTAAAATACA GGCTTGGATG TA'IMCCTGT TAAAGAAAAT AAAATGCAGA ATATTCAAAA CGTCTGACCA CCCTJ'CTAAG AAAATGCATC TCTGAGGTAT 'FITrCCTrAG AAGTTATTGT AAAAATCCTG GAGAAG = G AACACAGCAA AGCAAACAGG ATGCAGAGTr TAATCTGTGG AAAGCTI'AGG GAAGAAAAGC AAATCATTAA AAATAGGTCT TCCTCTGAAG A'TT=AAAA CGCAAAGAGG GTGGAATAGC AATGATAATA AAAAAGCTGG CATAGAGAGT GGCACAA'ITT GCTGTGCCAC TGAGCTGACT 50 GGATGTGTTC TGAA'I=CTA GGCATTAGTG TACCTTTCCA CACGCATTCT CCCTTTAAAA AAAATGCCCA CACACTGAAT ACTTTTCA TGCAA T7AA AATAAGCGCA CCATCTAGTI' TACAGAAA FT CACTAGAAGT TATTTATCCT AAAATAGCAG AGATCTAGAA GAATITGAG CTCTAGGACA 'TrTAGACAC ACAGAAAGAA GAATCTGGAC AAGTCTTGAC CAGACATGAC AGAATAGAAA 'TrTC'TrCC TA TrATCTC 'TTrGAATAAA AT=~CAGGA TCTT1ACAGTG GACAAGTTTG TTATCTACAC ATT1GTGAAGC ACATrGA'IM CTCCTCTGTA 55 GCCTrAGGAA GATCTGAGAG GTGACTGAGC TGAYrGAATG ATCCGTGACC GCTCTACTGG GACCAGTAGT AGAACTAC TGGTGGAGAC CTGCTGGAGG TFITGAGAGCA GAC'TTTGAAA ATTACTAGAG CTACACAGAT ACTGTGTGGC TAACTGGATT ATG'TrAGAG GC'T7CAGAA CTATGCTGCT GCTGCTGCAG TGTAGCCAGG ACGCACAGAG AACATCTAAG GCTCTTGAAT GGGGCGATAG GGACAGA'TrT CAGCAGCCAT CTGACTTCAG TGCTCATI GATGCTTTCC CTGCAGGGTG CAGTGTGCAG TGTGCAGTGT GCAGTGGTGG GAGGCTCACA 60 CAGGAATACT TGCTTCTGTA GCCCTAATTT CCGGTTCAAA CTCTGCAflC ACC'ITGACAG ATTC ITTCCT TGGCCAAAAT TTAGTTAGGC TTCTGGGCTT TCTCTTATGC CCACCTGCAG AC TT=GGT AAAATCCAGT TMAGTAAAG AGCTCTGCTA AGTCAGnITA GCAAGAATCC CCACCTCAAA AGTCACTATC TCCCTCCCTG GTAGTGTCTG GCTTGTCTTC AGCGAGAAYI' CTATTAGGTT CTGTAGATT AGAATCCTCC T~rACCCTTGA TGCTJ7CCTCT TAGTAT1T TCATCCACTG ACTCCTTGAC CCACC'TTGCT CCTCGGCTAT AAATrCCCAC 65 TTGCCCATAC TCTGCAGTA AGACTA'rlTr CTCCCCACTA CTGCAAAATC CCATTGCCAT GGTCCCTATA CTATCTCAAT GGTAATGAAT AAAGTCTGCC TrACCATGCT TTAACAAGTA ACA'FrGAACC A TTITCT TTAACAATCT GCTGCACAAT GAGA ITACTA AAAC'TrATT CCATI=GCC ATGCTGGATG TCCTCAATGG AATGGCTCTT GTGAGCACCA AATCATTGTG AGAAGGAAAA CCCATCTC117 ACAGCCCCCT GTAACGTGAT GTATGTTACA TGTGATGTAT GTrACATAGT 'TTTCAT GTTGATCACT 'IrGCCCAT TTTCCTATAT 70 CTTATCAGTT GGAAGACTGT GGAAG'TrGT AGTACTAAGC CACAAGATGA CTAAGAAGAG TTGAAAGGGC AAGTGGGGCT AAAAACAGAT MTG=TGAC TTACCCCACC ATTCCCCCTA TCATGGGGCT GAATCTGCCT GGAGGAAGGA GCATC'ITTAT C'TrGTACTG TGAACCACAC AGTCTAGCAG CAGCACAGCC AAGGCACTTG GGG'IMCATG AGACTAAGTA CATGCAATTC TAITGTAAAG GCTIAAAATA TATACAACTG ACCCYFGAAC WO 00/62736 PCT/USOO/08020 201 AACATGAAT'r TGAATTGCAT GGTCAGTTAT ACGCAGAT TCTTCCACCT CTGCCACCCC TGAGACAGTA AGATCAATCA ATCCTCTTCC TCCTACTCCT CAGTCTACTC AAAGATACTT GAAGTCTACT TGAAGATGAC AAGCACAAAG ACATTTATGA TGATCCAC'IT CCAC'ITAGTG AATAGTAAAT ATGT1TCTC TTCCTCCTAA TFITAACA CTICTTCTC TCTAGCTI'AA 1TATrGTrA AGAATACAAT CTATAATACA TATGACATAC 5 AAAATATGTC TTAGTrGACT G'ITATGTTA TCTGTAAGGC TTCAGGTCAA GAGTATGCTA TTAGTGGTTA AG TrTCGAG GAGTCAAAAG GTGTATGTGG ACTrTCAACT GCAGGGGGGT GGGCACCCCT GCCCCCATGT TGYFCAAGGG TCAACTIAC TGCCAAAGGC AAGCCTTTAC ATCCACTMT TCCATCCCAT CAGTAAATGG AAAAAGATAG CTACAGTATC CCTGCGTCAA ATCTTrTT 'I1GCAGATCA CAAATTGGCC ACTCACCTTG CTCTGTGAGG GGTAAAATGC CCCACTFTCT TTAGTAATAT TYrAAG ITAGA TAATATITAA G'rTATAAAGT 10 TGTTCTTFGT AATCGT]?AAT TGTAATT ACATAGTC 1TCAAACAG AAATAGCATT MT-FAGAT AACCTCCCGT ATAGATGATG AAACI'CC1 TAAGGGCTAT CTGAATTA ArrCCTTGAA AAGGCAGAAA TTGGATAGCT AGTAGTCATA AATGTACTGT GGCTTCCCCC AACCATCTGG GCTATATAGA AGCTGCATCC TTGGACTGCA GTAGAGGAGT CTTACAAAGC ACAGAGCAAC TTCTCTCCTG GGTFTGCGCTA GTI'ATGATGG CAATT-AAA TGTGTACTr TACCCAAAGA AAATCCTTAT TATCAACAAT CACAATGCCA TCATAACCAT 15 GGTATAAAAA A11?CAAAATG TCCCAGCTGA AGTGGAGGCA AAGACTCAAG ITCATGGAGT CAGAGTTTCC TrTGCTA'rrCC TC'TFICAA ATGACCA3TT AGTAAGCACC TGAAGAAAAT ACTATGGACG GCATTGAAAA GTGAAGATAG GTTTAATCTT CTCGAAAATC TAATTCTCCA GATGAAACGC TGACACTTAT CCACCCCACA GACCCTATAG CAGATGTGTC ACTGGCCATC ACAYMTGACA CAGAGAAGTC ATAACTCAGT CAGGACAGAG ACATTTCCAT GAGYITCTGA ACCATGGACA GAACGTCGTC TGTGGGACAT GAAAACTGGA ACTT1AGAGGA 20 CAGGCACATC TGAGAAATGG GCAGTTTAAA GGCAGAACAT AGCACATATG TGACTGGGTT 'TAGAAGCAA ATACAAGA CGCACTCTI'C TTCATCCTAA ATAATCTGCA ACCAAAGCTT CCAAAAAAGA CAATTTAGGA ATGCAGAGGT GAGGAGTAGG GAGGGGAATG GGATGAGAGA GAGTGGAGAT TAATGGTGGG CAGAGCGAGG TrTAGAAC'rr AGTGGTTTCT TCAGGTTCTG AACTGAAATT TGTATACTGT AAAGGCACAA ACACCA3TTT TAACAAAAGT GAGCAGGACT TCCTATCTGG TTCAGAAAAT AGGTGAATAA ATAGTACGAA TITATTAAAAA 25 TAATAA TTC CACTTATACA TAGGAAACTT GATAGGAACC ATGATAAATG CTTAACTCTT AATCrTFCAAG GAACTCTGCT AGGGATATAA TATTATAAAT M~GrI=GC AGATGGAGAA ATTGAA=hT AACCCAAGTT ATCATAACCC TTAAATGATT AAATGATACT G2ITACATGAG AAAGCTGCGT ATCTG FITCC TGGATPTGTA GCCATAATT GTGTCTCAAG TCCC'TITTGC TGCCAGCTAT CTTGGGTAGG TGTGTTCCCT TrGGGCTG'IT TGATACCCCC ACA'I1TATCT TIFIT=C TC TI"ITIG TTGAGAGAGT CTCCCTGT TGCCTAGGCT 30 GGAGGGCAAT GGCGCGATCT CGGCTCACTG CAACCTCCGC CTCCTGGGTT CAAGTGCTTC TCACGATTCT CT7GTCCCAG CCTCTCTAAT AGCTCGGATT ACTGGCATGC ACCACCACGC CCACCTAAYI7 'TGTAT1IT AGTAGACAAG GGGTITCTCC ATGTTGGTCA GGGTGGTCTC AAACTCCTGA CCTCAGGTGA TCTGCCTGCC TTGGCCTCCC AAAGTGCTGG GATrACAGGT GTGAGCCACC ATGCCTGGCC CCAAATTTAT CTTAATGCC CCAANITATC TAGTCCCAT GACTGGGCTT CTGCMTGAT C=T1CTGCA CTI'GCTGGAC CCTCTCCCTG 35 GGAAATGAGA TTGTGTCCTG AGCCCCTAGT TAGAGGCTAT GTCTCTGCTG TI1CCTGAATG GGCCTCCTGG ATGAGACCTC ATTAAAAGTC TAATrCTC'rT GGAGAATrGA GAGATACCTA 'TI'GTCTCAA AATCATTGAA ACCAATTAAT GTATTATGAG CCTCTATCCA GTGATTTGTA CCTCAATrFCC CCAATCCAGC TGTCAAGGCC AATTTG'FrCT ACCTTACCTA GTAGGTAAGT CTGGAATTGT AGCTGTGGCA TITICAGTAA TGGTACTCTA GGTTAGCAGT CCCCAACCT7 'TTGGCACCA GGGACCAGTT T-TGTGGAAGA CAATTI=CC ATGAAGGGCT 40 GGGCAGGGGA GTGGTI7rCAG GATGAAACTG TTCCACCTCA GATCATCAGG CATTAGA'ITC TCACAAGGAG TGCGCAAGCT AGATCCCTCA CACATGCAGT TCACAATAGG GTGTGCACTC CCATGAGAAT CTAACACCGC TGCTGATCTG ACAGGAGACA GAGCTCAGGC AGTAATACTC ATI17GCCTAC CGCTCACCTC CTGCCGTGCA GCTCAGTTCC TAACAGGCCA CGGACCAGTA CTGGTCCACG GCGCAGGCAT CAGGGACCCC TGYTGCTAGG TATAAGCATC TGGCTGCTGC ATGTC'ITCTG TGTAGCTACA TCTGTATGTG TATCTGATGA GATATAAATIT 45 ATTTGA'rrAT AAATTACTTT CTTCATATTA GAGTTGTGAA TGAGTATCAC ATATAATI'AT ACATAAACTA GGAATATGCT TTAATAAT GTATATAAGT AAGTTTCCTI' AACTATGACT TTCATCTTAG CGTAGTAAGA GGGTGCTAAG AAATATTTGT GATGAAAATA GGCATTGGTA GAG FTGAGAC CACTGGGTGA TGAAAGAGTG TAAAGA'TIT AAAGCCTTCA GATGCTGGTT CAAGGTGAGA AATGTGATTG GGAGCAAATC AATTAACTTC TrGAAGTCTT ATAGGGCAGT TATGAATACT TAATGY~rAAC ATATGTAAAG CTCTCTGCC CTGTATACAG 50 TAAATGCTAG TTAGCTATTA TGATCACTAC TAAAATGGGG ATGACATAAA CCTCATAAGG 1TlITAAGTAT TATGCAAGAT ACTATACAAA GTCCAGTAAA TATCACATTC AA TGAATCC ATGATGTCCG ATTA'IT=AG CTACT7ICCAA GAGAGAAAAA AATGCTGTCA G=FTACTGT TC'ITATAGAG AGCAAGGCAG ATCCCAATTC CCAATGTGGT AACGTGAAAA ITI=GCATr TGAATCAACA AAACAC'TIC TC= =rC'~ CCTACTATI AACAACTGGT AAGTCTATAC TCCCCCAAAT CTGGAATTCT CCTTTCTTAT TCTITTCCT CCTACCAAGA 55 CCGCAGGATC TITACTTGG CTATAAGGGG TAAACCTCAA GTAGTACAAG TTCTCTGTAT TAC'T=1ATA CTCTGTCACA GATTCCC T[r GTICCTCAT CTCCATGTGA ATITAGTTAA ATTCTCAGCA TTCTGATCCT TACTATACAA GGTAAATGAA TATAAAAACA AAACGAAACA AAAACCTCTT CCTATTTACA TAAGGCCCCA ACCTAATATI' TAGTGATATA TATVAATGTG AACAAGGAAC TAACGAAGAC TGGGAAGAAA FrCACAGACT TGAGAGAAGA AATGGCAGGA 1TTCCTGGGA ACAATITCAT GTAACGTCAA AGGTGGTAAA AGGTCAAATA 60 GAATGAAGAT GGAGAATACC GGATITCT-r ACAAAATGAT TFCCCAGGAG ATCTCATCAA ATGCACGAGG ATACCTTCTC AG'ITTCACCT AGTGAGTAAA AGACTGGTAA CATAGCTCAC TTACAATrTG GATAAACAAA ACTAAACAAA CAACATCAAA AITCAGAAA AAATAATAGC AAAACAGAAA TCAAACACTC AAATTrTTGG TCC FTCTGTT TATCATTT TGGATACTCA GTGAATG'rrA ATTAACCAGG AAACTTAAAA GTTATTTCAA 1TATGAACCT CTI'CAATCCT TCATCAATTA T1TGAGTAT TCTGGTCTTA AAAACATCTC TTCTTCTAC 65 AAACTTCTGA AAGAGATGAA CACCTCCACC TACACCAAAA TAATGTGCTT TGCTGGCCAA AAGTACACGT CCATITTTTAC TTAACAGTCT AAGGAAAGTC TGGTGCAAAT TACTATAATA ATCTGGG~rG TAAATGGTI17 CTGAGGTGAG AATGAGATCA TATITTACAA AAAG'TI=C ACTACTTAGT ACAAGCTTAC AAAACTCAGA CCACTCACCA GAAAAAAATC GGCATTTATA TAG1TGTGTI' ACTITGGTI' TCCTGCATCT tI1CACATCT GGCTCATITA CATCATITC TTCATCT-rCC AAAGTGGAGT TAGCTACTAC ArrAGGTAAG GTTACTTCAT 70 CAATCACCAT ACTGTTATAA TCTrGAAAGT GANT'T GGACCCTCCC TTGAATGCAG TrATACCTAG TAAACCTGAT CCACAACCAA GATCCAAGAC TITITCCCA GCAAATTTCA C ITTGGCCT7 TGTGAAATAA GCCAGGAGGT CAAAGGTACA TTCCCAGATT TTAAGCCTC CCTCATAAAC ACCTGTAATC AGATCAGAGT GAGAAGAAAA GCTI1TGAA ACTATGTIT CTCCAGGGAA GT-FCTCMFC AACAAGATGG T = CACTAC WO 00/62736 PCT/USOO/08020 202 TGATAACTTA ACATGCTGGA AACCTGGTAA TGTTTCTATG ACTATT CTAACATCTT CTITAAATCT TTAGGCATAG CATGCTCTT GGCAGCTCTC AAGGAGGGCT GT=TCCATG TGGCTCCAAG TTCCTTGAAC TGCTGGCTGC ACTGAGTGGA CTGTCTGTGT CTI7GAGAGGG AGCTGCATr7 TCCA'ITGACT TATGTTCCCA CAAGTGATCC TGAGGCAAGT CAAA'rrGTrC TGCAGAACAT 'ITCTGTCCC TCTC'I1CTCC YT-GACTT 5 TCTGAGACTG ACAGCTC'Tr TGAGGAATCC AGGGTCAAAG CTCCATCTCT AATGGGTGTT AATTCAT1TT CCAGATGGTC TTCTATAGTG AAATI'AAACT GAAAGGTCAT CCTCTrrATTA AATGCACACA ATCTITAAAT TCAGATTCTT CAACY-FCTGG ATAGAATG ATGATACACA CAAATCTGCC TCAATTATTC AATTAGT1ITT GTTGGGCCCA ATTTCTC'TT AGCAGCT71AT ACATGGTAAC AAATATITAG AGATA'I=CC AAATGACI= 'ITAGACGTCT TTGGTCCTCT TTCCAAGCAG CTCTGGAAAG AAAAAAAAAA AAAAAAGAAA GAAAATGATG 10 ATrAAAGCAA AATGGCACAT TI'CACTAAAG TGTAATA~rA AACAGCCACC CCCACCCCTC CCTGTCCCAC CATACAGCTG CT11TCTTA AAAAGTrGTG GGGAAGAGAG AGAGATAAGA GAITrGGACA CTCATACACA CCTTAAGGGT TCCAAAGTGG GAGAAGAAAA TCAACTATAA AAACAAACAG AAGAACAACA GCAACCACCA CCACTACCAC CTGGACAAAC ATAAAGTCCA AGATATrCAG ACAGGACAGC CTAGCTACTr GCTGTC7TC AGCTGTCTTG ATITGTGTCC AACCATATTC ACCCCCTAAG CTTCCAGAAT AAC'ErCACTTr CTGTCTITTrA 15 CAGAAGAGGT GCAGTATTT ATI=GGTAA GTCAGCGTCC C'TAAAAAC ATGCATAGGT ATGGCCTGGT GTGTGTAAAT TCATCCAAGA CTTCACTCCA AACA'IMAGT CGAGAACAGC AGCCCTAAGT GTATAGAAGT GGGGGTAATT TGGCAATAAT TAGTAAAGAC TAITrCGGTG GCAGAGCAAA CGCAAACTAG GGCACTGCAG TAGTITrGGAG AGACCTGTAG AAATAAGAAG CAACTITTA17 GAGAATCTTC TATCTACTGC GCTAGACACT ATACCATCTG CCTCAA'ITI' CACAGTrCTG GCAAGTGGGA TC'T7GTrCC CTPATACAA GA'IMACAAT 20 TTGGGGGAGA GGCGGGTCAC CCAGTCCCGC GGCTAGGAAC GCGCCTCTrT CCTCTCCCAT CACGCTGCAA GGCTTGGAGT CAC'FrCCGGC TGCAGGTCCC GGAACAAATC CGACCCCAGA AGTGGGGACT TCTGGCCCTC ACCTCCCCAT TrGAATGTAA TGTTACAGT GATCCAGACC TGGGGATGCT TGCT[CCCGA CGTGTCCTGG GATCGCGC IT CTGAAAAAGC TCACCTCACA ACGCCTCCTC CGGACCTAAA TCGCGCACCA GTGAGTCGAG TCCTCCAGGG GCTAGAGAAG CCCGAC ITTC TTTCCGGCCT TGAGGGACCC GGGCTCACCA AGAAACCAGC 25 CGCCCTCCTC TCTATGG'Tr TGGAGCCGGC GGAGAGCGCG CAAGGGTTGG CGGGACTGCG AGTITCCGGT CTGGGCnITG GCGGGTCTGG TTfGAAGCTC TCCTG'TrGA CGAAAGTATG TCTCAGGAAG GTGCGGTCCC AGCTAGCGCG GTTCCCCTGG AAGAA'FrAAG TAGCTGGCCA GAGGAGCTAT GCCGCCGGGA ACTGCCGTCC GTCCTGCCCC GACTCCTCAT ATCMCC~f GGTrGTCACT TCTACCTAGA GAAGGGTGTG GGCGGGTCGC GAACC TTCT CTTCTGTCCC TTCAGACCCA CCGCCAGGCT GGGTTATATT ACCGCGGCCT GAACCCCCTC 30 TMTITTGT CAGTGAGTGG GATGAAAAGT GAGGGACTGG AGGGGAAGCG ACAACCGTGG TAGATTTAAG TAAGGCT=G GCCCTGGAAA GCCTCGCGGA CGTGTTCTGA CCCAAGGTIT TAGCAGTGGA TGTGGCG'ITr TCTTCCATI'C CTTC TT7CAG TTrTCTGTA CTCGTTGCYT GCAATTAAGT GTAAATACTI' TTGCTAGTGG ATAATGGGGG AGGCAAGGAC TGAGACCTGC GGTATGACGA TAGCTCTGGC TCTTAATAGT TTGAGGTAAA GCGAGATACT CTGAGCTT GTCTCCCGTA AAAAGGGTGG TGAATATGAA TAAGGGC'= CTTAGCGTTA 35 TAAGAATTAA AGGGCATAGT TCTGTGGTGT GAAATC'TrA AAAGATGTI7C AGTAAATAAA AATGA'TrrC CTCCTrFCCCC TCTCAGACCT CTI17CTTC 'TTTCTT TITfTTGAC AAGTrTCTCAC TCCTCTCACC CAGGCTGGAG TCnI7CTGAA AGAG'rrC'rC CGCTTGTTGT TGGCT=CAA CTG FrGGATT TGAGGCGCTT AGCGCCTTCT TCGTCCGGGT GCAGCACAfl C'I1GATTGGT CTCATGCCTT TGTGGTIGTA AATGTGCCTG GAATCCTAGC C'1TTCATGGT AAACCATATG TATATGTATC TPCACAA CATTTGAGCC CAGCTTTATA 40 CAATTACACT CAAAAGAAAA AAAGTAACCT TCACTTGAGA GAATCTCAAT ACTGCACAAA TATTGTGCAG CTAAAGCCCT ATGTAATCAC ATAGAAGTCA TT1CACCTAGG CATI7AGCAAA ATCTCAGAAG GTGCCAAAGC CCCCTTIT AG T=GTG TAGGTACAGA ACTGCCGTCT TCAAGGAGTT TCAACTTGAA AACAAATAGC CACCCTCAAA ACATI1CAAAA ACACTT1AAAC TGCGTGCATA ATGTGTGTGA GACATGGTGT TAGGCYPTGG GAGAACAGAG ACACGGAACG TGATTCCTCT TCTTCCCCAC AAGCTTATAG AGAGACTTCA TTAAGTTGAA 45 AGTCAACA'rr CCCACCTAGC TITGCACTTC AAACGACATA TTCAAAAAAG CCCAAACTC CTCTAGT= CTCATCTGA GTAAATGGTTF TCACAAACTG AAACCTTGAA TCCTCTCTGT CTCACACACC CGATCAGTAA GYI7CTATI7GT TTCTGATTCC AAACTATGTC TTGAATCAAT CCGTTATCT CCATCCTCAT TGCIACCACT CTGATTCCAA ACCCTTATCA CCTCTCACTT GGAGTATTAA TAGTCCTT GM~CTACTC ATAA'rrCATT ATTrCCAAAAA AGYFAAGAGG GGAAAAACAT AGATCTCGTC ATTCCC'TT TTAAACCACT TTACCTTCAA 50 GGTTCCAGGT GATCTAAGCC TTGCCC'T7CT CTCATACCTA GTTAATTAAC TACACTCTGT TCATGAATAC ATTAGGCTCA CCTACCTCAA GATCTITTTTG CTCAGCCTGA =TGTTCTCT CAGCCTITG CATATrTCAT GTmTATGTCT TGGCCCAAAT GTCACTTCCT TAGAGGGGCT TITCAGAGC CT-FCAATCTr AGGCAGYJ'CC CCCAAACGCA GTCTTACACT TGTATCACAT TGGCCTGTTC AGTITI'CTAA AAAGCACATT ACCATTAAAA GAAATGCTCT TGT~rGCTTT GTATAT1T7C CACTrCTACA CATrATGYFG CAAAGTTrCAT AAAGGCAGGA 55 TG FFGATITT CTTCACAGCG TTACCCTCAG CACCTAGAAC AGTGCCTGAC ACATAGTAAG CATrCATrAA AGGGCTAAAA ATATTTCATG ITTAAAAAT ACTGGGAGT CTAAT1'AGAC AATACTTI 'rrCAGC'JTAA TGGTAGTAT11 TrAGC'I1CAC TA=IIAACA AATGAAAAAT TrGCAATAAA TCTACAATGC CATrACCCCC CAAAATCTTT 'I1CATGTI' GCAITPTACG TATrA'F=C CAGGCCTJ7AC CTGCATGTCT GCATAATCAT AACTGACTAA TITfGGAACA GCTGGTAATI' AMfGAGC1T TACTGAAATT TITTCATGAG GCCAA'rTCTA 60 CCCTACTGAA CTCAAA'ITTG AGTI7AATGAT GACCTCATTT TGATFrGCTGC TGTAAAAAAT AAGATITCGG AAGAGGAATG AAT-rCTGTA TI'ACTGTGGT AGGACTATGG GTPTITT G TFG'ITGT TTGT=TGAG ACGGAGTCTC ACCCTGTCAC CCAGGCTGGA GTGCAGTGGT GCGATCTCAG CTCACAGCAG CCAGGYTCAA GTGATrCTCC TTCCTCAGCC TCCCGAGTAG CTGAGATTAC AGGCACGTGC CACCATGCCC GGCTAATFTT TTGTATC'Tr AGTAGAGATG GTTTCACCAT GTTGGCCAGG CTGGTCTCGA ACTCCTGACC TCGTGATCCG 65 CCTGCCTCAG CCTCCCAAAG TGCTGGGACT ACAGGCGTGA GCCACCGTGC CCGGCCGGGT TATTCATTIT TCTrATrAAC ATrC'ITTGAT GAFI'CTI'ATG GTGTTGTTAC AGTAAAACAT TI'CTAACAAT TATTCTAACA ATI7A'I1C'I1G ATGGTGTATA TGAAGAATI1? ATTGTCGTGT A'IMGTAAGC TGCTATGTGC AGAAGAAT1 CAGTCAAATA AAGTTGGTAA GATAGGTATG TAAGTAATAT GAAAAAAGAT AGAAGGTGAT GAGTGAC I1A GGTATAAATI' AAGTACAATA GAAATGTI'GA GGAAAGAAAA AKITrGTA ATAGAAATCG GAAGTACAAA 70 CTGGGCATGG TGGTGTGCAT CTCTAATCCC AGCTCCTM7GA GAGGCTGGTA TGGGAGGATC AC'ITTAGCCC AGGAGCTTGA GGCTGCAGTG AGGTGTGATC ATGTCACCGC ACTCCATCCT GGGTGACAGC AAGACCGTCT CTCTTTI1 TITTT=GA GACGGAGTCT CGCCTATGCT GGAGTGCAAT GGCGCGATCT TGGCTCACTG CAACCTCTGC CTCCCAGTFI1 CAAGTGATrC TCCTGCCTCA GCCTCCTGAG CAGCTGGGAT TACAGGTGTG WO 00/62736 PCT/USOO/08020 203 CGCCACCATG CCCAGCTAAT TA'ITGTAT TI17AAGTAGA GACGGGTTCT CACCATACTG GCCAGGCTGG TCTTCAACTC CTGACCTC'IT GTTCGCCCAT CTAGGTCTCC CAAAGTGCTG GGATTACAGG TGTGAGCCAC CCCACF'rGGC CCCGAGCGAG ACCCTCTCTC TAAAAAAAAA TAAATAAATA AATCATAAAC CTGTGGATTA TTGTAGCATT G ITCTCATC TGTCAAAAAT ATrCATGAC TATGCATAGT TTGAAAAGGC AAGTrGTCC 5 CTGGGCAATT flCAAAATAT TTC'=AATG TGTTrCACA ATACTG'TI'A CCTAATAAAT CTTAAG =T TAAAAGCAAA ATTAAGCCAG TAATI'TGAGT CCAATrCCAA TCTCTTATGA GTCATFTGCTr AAATICAAA AGGGTI1AT TlrTITA GG'IrrGTrCT GAGTAATGAA TACCCTATTA CTATGATACT AGTATC FTCC 'rTAAT-rATCC TACTCATI7GT CTCAACATTC TGACAG117GG A ITGAGCATA ITrCGTAAGTA AAATTG'T=1 AACTGTATGA TGTAC =GA TG'TrAAGGTC CGAGTCCCCA CATACCTCGG TAGATGTGTT CTrACAGITTT 10 TGTATTCCCT TGAAATGTAA CTGTTCTCTA TGTTACAGCC 'ITTATAACCT TCAGTTACTT GAAATGAACA AATTCATTCA AATTCCAGCA C'ITAAAAGT T 'TAAATTACA TITGGATAA ATACCAAAGT GTITTTGTGA TGATGTATGT ATAAACAAAT TGTAAATATT1 AAACGTTAGT TG'FrACGATV AGACCTATAT AAAACATGAT ATGCAGTCTA CTGAATAGCT ATCAGCCTCT AACATG'ITTA GTGTCAMTA GAAAATGCrr TCTAAATTGC CAAAAGCTGA TrGTCTAGGT GATAACAAAT TTACCATITG GAGGAAGTG ACnI7CTCAT TITCATGTCT 15 TCATCAGTCT TACTTGATGA GATTCATTCT TCTAGTCAGA AGAGAGMIIA GACTGCTCAG 1TACTCATA TITTGAGTTA GCTILCTAT TTAGAGTTCA CTTGGTTGTG GAATA3TCAT TTATAATG AATCTACGYT GTGTAATGGG ACCTAATII 7=I~CC1T GTITIGTIG GAGTCTCGUT YrGTCACCCA GGTTGGAGTG CAGTGGCGTG ATC1TTGCTC ACTGCAACCT CCACCTTCCA GGTTCAGGTG ATTCTCCTGC CTCAGTCTCC CAAGTAGCTG GGA'rTACAGG CATGCTICAC CACGCCTGGC TAAIT1TGT AT1TAGTA GAGATGGGGT 20 TTCACCATGT TGGCCAGGCT GGTCTCAAAA CTCCTGAGCT CAAGTGATCC TCCTGCC'rrG GCCTCCATAA GTGCTGGGAT TACAGGCGTG AGCCGCTGAG CCTGGCCCCA GAG'ITTG'TT TG'TrTG'I TCAAGACAAG ATCTCACTCT ATTGCCCAGG CTGGAGAGCA GTAGTGCGAT CATAGCTCAC TGCAGCCTGA ACTCCTGGGT TCAAGCTATT CTCCTGCCTC CATCTTCTAA AGTGCTGTGA 'ITACAGGTCT GAGCCATGAT GCTTGGCCTG TG'TTMGTT TG'ITG'1T GGGGGACAGG GTCTTGC=T GTCACCAAAA CTGGAGTGTA GTGGTGCGAA 25 CATAGCTAGC TCACTGCAGC CTCCATCTCC CACGCTCAAG CAATCCTCTC ACCTCAGCCT TCCAAGTAGC TGAGACCGCA GGTGCGTGCT ACCATGCGTG GCTAATTrrC TAiTTATATA 'TFATPT GGTAGACATG AGGTCITFGTC ATGTTTCCCA GGTGGTCT[T AACTCCTGGG CTCAGACAGT CCTCCCGCCT CAGCCACCCA AAGTGTTGGG A'ITACAGGCG TGAGCCACCA TGCGTGGCAT AA'TTTI' AAGTAAATTA TITITTPrATC 'rTGAGTATAG AAGTGATTCA TGTI'CATT1GT GGAAAATATG AAACATATAG AAAAACAGAA AAGATTACAA 30 AACATCTAAT CTGAAATGGT TAAGATTG ATGAGAACAG TCTCATCTCA TICCGTATA TTCCTGCCAG CCTATCCATC A1-TCTTCGTA CATGYITATC TACA I7AAAA YFGGTGYFAT A'rITFGGAAA CTfFTTGT7 AACTACATTG TGAACATII TCATGYIIA AAATGTCATT 1TAATGATGG CAGATCCTAT TCAATAGATG TACACACACC TA'ITTAACTG GTCCACAATI' G'PTGGATATG TAGGTCG'TF CC'ITTCTCTC TTTTTT 'TTMGGCTA CTACTI'AATA GTrTCTCTGT ATAGAATGTG GTATITGAA AGTGTATCAA GC'TFAGATT 35 GGTAGTATTC F[GCA'ITTAA TAAAGGGCAG TGGCCITGT TGACTGACAT GACAATAM T'TATAAAATT TGTTIA'TFGC 'ITACAGAAA T'TTGAAAAT TAYI'GTAGAA ATG'TITIAC CTCATATGAA CCACCTGACA TTGGAACAGA C'TFrC=IIC ACAAGTGTTA CCAAAGGTAT AATACTATTA CCTGAAAATA CATGTI'ATAA GGAATCTAGC CTCAGTC'LTA GATGA'1TTAT TATTAATI7AT GGCTCTCTI17 TT1CTAATATA TCAAATATAT TCAAAATAAA AATAAGGAGT AAGTAGATCT CATGTGAGAC TATAATGGTG 'FFAGTGTGAT CATITAGGCAG 40 TI7AAAAACTG TTACAGGCTG GGCACGGTGG CTCATGCCTG TAATCCCAGC TCTCTGAGAG GCTGAGGTGG GCAGATCATC TGAGGTCAGG AGTTCGAGAC CACCCATGGT CAACATGATG AAACCTCGTC TCTACTAAAA GTACAAAAAA TTAGCTGGAC ATGGTGGCAG GTGCCTGTAA TCCCAGCTAC TFGGGAGACT GAGACAGGAG AA-fFGCTIGA GCCTGGGAGG CGGAGGYI7GC ATT1GAGTCAA GATCGTGCCA 'TGCACTCCA GCCTGGGCAA TAAGAGCGAT GCTCCGTCTC AAAAAAAAAA AAAAAAAAAA AAGAACTI'AT AT1TCAGAT TGTGTGGFJC 45 C'TACTAAC TGAATI'AAA TTA1TIGTAG TCAATIIAA ATGCTCTTGT A ITTAAAGC CACTGTACTC CAGCCTGGGT GACAGAGTGA AACCCTTAAT TCAAAAAAAA AAAAAAAAAA AAGAAAAGCT GGAATATTGG CAAAATCAAG TAACTAAGAG AAAACATTAA ATI'CACAGAA TACATTAiTA CATI7FAGAT ATATATGGTA TATGTITICT CTGAAAAGCA CAAGCATACC TTTGTIT TAAATGGAGG GAACTAAAGA TAC'ITTGGTG CCAAAATGAA ACATTATTG TAA ITAATCT CTI'ATTGAAA TGGG'TFTCTA ACT1AGCTT TGAATCGTAA 50 TCTICAAAT TrC'TFGTACT CATAGTCACT TGATGA'rTCT CTATCTGAAA TA3TTCFFAG AA=TGTI7CT TGACCACCAG AAAAAGATTC AACTGTrACA TAGATGAAAA TGGATGTTGA GTGTTAACAG GCCTATGGGA AACAGTATF TC'TFAGCTA CATI'GTA'ITG T-FGACTGTGT TGCTATTrCTT ATAATG TFTA GGTCA'ITTAA ATTrGTTAGAA AGATCCAAGT ATTAAGATCT AGGGTGGCTA AC'rITTCACA GACAAAAAGC 'PrGTTGTAA GGTCA'ITAC TATACCC IA ATTCAGGAAG GTTAGC'IGA AT7GGGTCAA AAGGAAACTG GYI'AGAAAAT 55 AAGTGAGTAG TGAATAGGCG ATTCAGTGCA AAITCCTICC AGAAAATACC CTTGTAAATG ACTGTATGAA TGTGGATI'CT TCAAGACAGT CAAA'1TTA'IT GTGCGAAAGT AATACTIIA 'TTFGCAT CTCTAAAACA TGAAC'ITTGA GTGATTIT AAAAAAATTIG ATGCTA'rTAA ATAGATI'CAA ACCATAGAAA TGGAAAATAA AT FCTG'Tr GGGGC'IIG GGGGGATTAT G ITGTAAAAA TACCTICT CTGTA'TITG TGCTAATFA GGTACAATTG TTAAGCTAGA TGATAGCCTG TGGATGL1AC TAGTGCAAAA TCAAAYFATC GTATFGTGTT 60 FI'CTCTGTAA AGTIIGTCT TGTCTIICT AGTGA'T'CT CT1'ATI7CCTG 'TFATTACT7 GA'TI'GtTI' TACAGACTGT GAAATTA'ITC GATGACATGA TGTATGAATI' AACCAGTCAA GCCAGAGGAC TGTCAAGCCA AAMTTTGGAA ATCCAGACCA CTCTAAGGAA TATITACAA GTAAGTCAAA TGTATTAGAA AGCAGGAGAG AGAGGGAGCT TAAAGAATGT CAAAA TITI ATACTGATAC TGATTAGCTA TGTATI'CYIA TGTAATGGCC TAATGT'GGA ATI'AAA'1TTA TAGAA1TAAA GACGTGAATA TAGAAACATG AATTICTGAAT AATAAACTCT 65 TATAAGAAGA GAAGTCATCA AGCTAGCTGA CCCTACCTGT ATT1TCAAGG ATATGTGTGG AACACCTGCC ATGTGTITG AAG'ITGTGT TAGTA ITCTA AATGGCTAGA CAGT17GTT1CC AGTA'TFGTA G'TFCTGATAG ACTAAAGTTC TGTGAAAAGA GGAAGAGACT GTGTI7GTI CATTGCTGTA 'TffGTAGCAC CCAGCATGCT GACTAATACC TITTCAGTGC ACAAAAAATA TATTCTAAGT GAAA'TTTCCT TCCT11ATT1CA CAGACAATGG TGCAGCTCTT AGGAGCTCTC ACAGGATGTG TTCAGCATAT CTGTGCCACA CAGGAATCCA TCA=TGGA 70 AAATATTCAG AGTCTCCCCT CCTCAGTCCT TCATATAATTI AAAAGCACAT YFGTGCATFG TAAGGTGAGT AAAGGTCTAA TTATACT=G AATGGTATAT AATCAATGTG CATAGGGGCT GAGTAAAATA ATG'FITGTAT AAGATITAC A=rTAGTCT ATATI'ATTGA AATAAACT' TCCATAGAAT AAAGAACATG TAAGTAAATA ATTGTJ7GCAA AAAAAGTGGT 'TFAAGGAAG TCATTAAAAG TGGC'TITIG GGGTT1TA GTI1?ATC'T WO 00/62736 PCT/USOO/08020 204 ATrCCCCTC TATAAAGAAA GAAGTITAA GAAT~GTGT TGAGACAGAC ACAGGGATCC TGAAATAGTr ATGTCATGT17 GCATTGACCA ATATTCAATT ACCA'ITATGA TTAGATGTCA GAACTTCCTT 'FrATAAAGGA AAGTrAATCC 'rrATrAGTC CATCTCTACA TGCCAGAGGT AGCCTrGAGG CACAAAAGCT TGCCTAGAAT TTATGGGTCA CAGACAGT TAATATTGCT AT~GTTGGG CGAATGAAAA TCACTAGTTA ATJAATACCT 5 CTCTITGCTG ATAGGATGCT AAAAATGTCA CGCACCTGGC CTAATGTrAC CCTITITAG TlrCTGTATT~r GCAAGATCAT GGAAGTCAGA AATAATAT TATACATGCT TGCATCTCTT GAAGCACACT ATATMTAATG GATGT'rCACT AAACAATGAA TGAATATGTG ATT]CAGTAAA TITATGATCT CTAATAGTAT GAATTAAAGT AAATTTGcICT C~rGAGC'= GATTGTMT TCTCTCATT MTA1TATC CGTAATCAGA ATAGTGAATC TGTGTATTCT GGGTGTTIAC ACCTAGTI1C AGACCTrCTC CAGGCTCIT TCAAGGAGGC CTATrCTCTT 10 CAAAAGCAGT TAATGGAACT GCTGGACATG G'ITGCATGG ACCCTTTAGT AGATGACAAT GATGATA'rr TGAATATGGT AATAGGTGAG TGAAGAAAAC 'T]?CTGC'ITA GTATATGGTG ACTATAAATC ATGTATCAAT TAAAATTGTC TCTAATGATT CATGTTATIT TCTI'ACTAAT TATGCATI'AA AATrGA'TrA AATCrrACCA AATAAATTI' TAATCTTGAA ATIGGAAIT TGTAAAAM A1TFGGGTA CCITAACCTA GAT~GCGTA MTAGTrACT GTAATI'CTC CACAATGATI1 AACITATATA AC'=ATAAT CTCTGAGGTr GTCCATAFC 15 AGAGACAATA ACTTTCACAT TTAACC ATAACTGATA TTGAGATGCA GTTATKT CCTTCCAGAA TACATATAAA TACGTGCATA TGTGTATGTA AATATGTCTA TTCTCATATA CATATTATAA TGAAATAACT CATITTACAT GTGATGCACT TTATACTAGT TI'ATI1AT TrAII-AT TITTGAGA CAGAGTCTCA CTGTGTAGCC CAGGCTGGAG TGCAGTGGCA CAATCTCGGC TCACrGCAAC CTCGCCTCCC GGACTCAAGC GAI17CTCCTG CCTCAGCCTC ATGAGTAGCT GGGATTATAG GCGTCCGCCA CCACACCTGG CTAATT=TG 20 TA~T=~AGT AGAGACAGGG TTTrCACCGTG TTGGCCAGGC TGGTCITGAA CTCCTGACCT CAGGTAATCC ACCTGCCTCA GCCTCCCAAA GTGCTGGGAT TACAGGCATG AGCCACCGTG CCCAGCCAAT ACTAGTTTAT 7TIAAAGAA TrGCTGGTCG TAACACACTI CA'rrGATTr ATCACTCATT AATGGATTAT GAACAAGAGT Yr7GAAAAACA ATATAAAGGC AAAGYI1GCA TrCAAAACTr TGGTATAAAG AGAGTAAGIT GG'TI1TGTGC AGTGTATCAG GCACCTGTTG CTCTGCAACA CACCACCTCA AAATCTA'ITT ATrCACTA'rT TA1TATTCA 25 TGATTCTGTG AGTCTGCAGT 'FrAGGGTGGG ATGTCCTGAG ACAACTTCT CTGATCCACC TGGGGCACTA GCTCACCCAT GTGACTTCAG TGACTTCATT CACATCTGGC TGrrGGCAGA GGCAGAAGTA CYTGAGAAAG CCATGTGCAT CATCCAGCAG GTTCACCCTA TCTCAGATAC CTGATGCCAG TGGTTrCAGG GTrTCTAAGA GTAGCAAAAG TGTGAGCAGG TCGCTGTGTG CTAGCAC1T TCAAGTITCT G3CTTGCCTTA A'rTTATrAT TGTCCCCCGG GCCACAGCAG GTCATAGCGT TTAGCCCAGA GTCATTGTAG AAAAGTGTGG ATTCACAAAG 30 GGCAGTCATT GTGGCCA=TIT'1ATAAATAA TCTACCACAG ACTGAGTAAA AGCC'ITGCAT GAATACCATG GATA'ITAA' TGAAY]7CTI1C CTTIAGAT TTTfCCT TAGCAATI7G TITTTGTCATT 17GGATTAGA ATTATATCTG TAGAATATr CAGTrATAAT AGGGTACAAC TITATTCCA CTGAACATCT TTAGTITTAT TrAGGTCATC TGGTAGGTAT AAACTrCAGA AGTrAATATr CAATA'TrrAT AAAAACCATI' AACAAGTGTG ACA=TAAAT AGT-rTAAATA ATTCTTTGA CACAACTGTT TCCAAGTTGT G'JTACGTATr TTAATTCAAT 35 CAAATGTTGA AA17G'I7CAG TAGATAG=II TAA'ITATAGG AGAAACTCAC CCCCATGACA 1TTGGATGTC TrrAAAAG'rTC TG'TATCTTT C'TrTGCAGTT ATrCATrC'r TATI'GGATAT CTGCTCTGTT A=~CCAGTA TGGACCATGC A'IMCATGCC AATACTTGGA AGTrATAAT TAAGTAAGTT TGTTTG FrAT TTEACrr TTAGAAAATG TITCCATAT TCCCCAATCT TAATI'ATI'CA TGATTCnI7A GATI'GCMTT AAAACATTI' GTGTGAAT'17 AATGTTCACT GACACTGCTG TCTGATAATC CAGATATTCT ACATGTAGCT CTCAAGCCAA 40 ATTGGACTTC 'ITTACCCTGT GGCCTCTAAA ATI'AAAAAAA ATGTrCTTCC TAGTFAGCTA GTACTTCAGA AATAATGGGC CATGGGCCAG ACTAGAACT-F AACCACITI CTTCTGCTAC TGTrGTrrrAA CCAGCTATCA AGTATCCTAT TTCTAGGATT AGATAAATTG ATAACTATAA ITAAAACTGA ATATAATCTT YITCAT-FAGGT ACYITAAGT TGTTCACACT TAATT7CCATI' TGTACAGTAA TITJ7AAC'T1 CTGAAACTGA AGCATITTAA AGGGTCACCA GGGATAGTGC CTGTAGCATT CATCAGiAT7C TTAGGGGTGA GAGGAGATGT GGTTGAGATG 45 TAAAAATGGT TAAGAATATC TAC'TATAC ACATACATAA AACATTAAAG GTCAGTGTAT TI'TCAGGTCT TAGGTACTTT TC'ITGTACTA CCAGGACATT AAGYFGCCAT TCAGTGGTA AGAGTG'I17GC CTGGGAGCTG TATCACATGT GCTTAAATCC ATI'CTTGAAA TCATFITACTC CTTCTGAGCC CTTGGGCTAT TrGGI1'AATr TCTCTGAACG TTAGTTTGCT CATCTGAAAA TGGAAATAAT AATAGCAACT TCTTGACAGG GTTATAGTGA GAATTGAGTT CATCACTGTG AAATGCTTAG AAATGTGCAT GACACATAGT TAATACTCAA GGAATTAGCC 50 ACATCACTAT CATCATCACT GATJ'ATCITC CACTC'I7ACC CTCTTCCAGT TCATI=CTG CCCAGCAGAA TGATCYT'TA AAAAGTAAAT CAGATCATGT TACTCTATTG CTTGAAGTCT ATCCCATG ATT1AAGAATA ACAACCTAAT CCTCTGTGGA TGCTGCCTCC TTCACCAGCC TGTCTCATGC TGCTCTCCCT ACTCTTAGTr CCTCAAACAT ACCAAACTCT CCTGTCCCAG AGTCTITCG TGGTI=CC ATCTGCCTAG GATGCTTCTC TCTCCTA TTT TGTGTACCTT GCTAACTCCT GCT7ACTGTC TFITCAGTTCT CAG=TAAGA GTTATATCTT 55 CATGATAACA T-rCITTGATA TCC'I1ACCCT AAGATTAAGT TAGATTGATA TCCTTACCCT AAGAATAAGT TAGATI'AGGT CTCTCTAYFG TAGCACCTTA GACTCTGTCA TIGACAAAT CACAGCCCTA ATTAATFATT CTrAAAATTA TrTAACA'ITC TCTCTCATGC TAGACCACAA GTTTCATGCA GGTAAGGCGG AGATTGTGTC CATrG'rrG ACCCC'=GT CTCCAGGGCC TGGTAGAATG CCTCATACAT AGTAAGAATr CAATTAATAT TTTACACAGA GAAAAAATTA GCAACTTATr TAAACAAATA TAACTGCT7C AGAGGTAAAC TGGGCACATC 60 TI-AGTTATAT TATGTGATAT ATGATGCTI1' rGATTG'TrT TITTAAATGT TCTACAAGGT AGATATrGTr AGAGGTCCTA AGTTACTTGA TGTGTTACTT GTGGTGAT7G TATTC'II1C TTh'AT[CA TITAGGCAGA GCCTTAAGCA CCAGTCCATA ATAAAAAGCC AG ITGAAACA CAAAGATATA ATTACTAGCT TGTGTGAAGA CATTCTTC TCC'ITCCATr CT-rGT'fACA GTTAGCTGAG CAGATGACAC AGTCAGATGC ACAGGTAAAA ITGGGCTAA TAGCATITA AACAGCAACT CTTATITTCT TTGGCAGTTA GTAAATCTCA TI1XAATGTC 65 TGGGTCAGTC TKITTAAGAG GA=IrAATT TATCA'rrr GGGTGTTI TITGATCTG TGGGATTATr TATATCCCAT AATTACTTr CACCCAGAGC ATTGTA'ITAG ATTCCTAACT GCTGTCATTG CCTCTGGGGT CTGCCTGGCT CCCTCTTGC FTGGTAACTG GTTGGTCACA GCATTCTTCT CAGAATCCT17 TCATrrC'TT CTGCATGAGA ACAAAAATTC YT=GTTCAT A TTGTATAA GATCTGATAT AGCTGCAATC AATCTTGCAT 'ITCTTCA CCAACGCATT GCGACCTITA GGGATACAAG TATGTTTGTG CATGTATATG TATGTATCAG 70 TCT1TTAAAT 'ITGATATAGT CATACATTTG T=1]A=II GAAAAG'ITAG AGTGTTGAAT TGGTATCCCA ITTATGAAAC A'rrATATTCT AAAAA ITrGT AGTACGATTA TTGGGAATFA TAACTCATT TCCTGTAACA CTGTTATACA TAGTACCThL' TGQTTTCAGA CTAGCCCTCA A=IIA IMA ACTATAGTAG TCCTAAATTA TAAGATTAAT AGTACTCAGG ACCTAACAGT TATATGTCAT TTGTTITT 'TTTTGAG ATGGCGTCTC WO 00/62736 PCT/USOO/08020 205 ACTCTGTCAC CCAAGCTGGA GTGCAGTGGT ATGACCTTGG CTCACTGCAG CCTCTGCCTC ACGGG'FrCAA GGGATCGTTC TGCCTTAGCC TCCTGAGTAG CTGGGAYTAT AGGCGCCTGC CACCACGCCT GGCTAA'TTTT 'IMAGTAGAG ACGGGGTTrC GCCATGT7GG CCAGGCTGGT CTCGAACTCC TGACCTCAGG TGGTCCACCC GCCTTGGCCT CCCAAAGTGC TGGGA'ITACA GGTGTGAGCC ACCGCGCCCA GCCTATATGT AATAAT'TrA 5 ATGGGACCAT GAATTGAATA TflTCTICCTTl GAATAGCAAT GACATAGCCC CTrCTA'rrGT ACATCTGCAA GCTGATACAG GGAATTCCTT TGTACCTGCG CTCTTCCCTG CCAGTCAGCT ATGGGGGTGA AAGTGTAGGG GTTCATCCAA GTCCTAAAAC TGGTAGCAAC TCCTAGGGCA GGGCTGATCT GGAAGGACAG ACCCTAGGGG AGGGTGGAAC MrAAAAAGA AGTTCTGAAG GTAGTAAGAA GGAAATGAGG AGTAGTGTTA GGAAGGGGCT AACTITITC TrCTrGC'rC TCTCTTAT CTCACCTGCC CCTCCCC'TrG TATCCCTTCT TCC'I1TCC 10 C'rrrCCTr rTGTCCTCAC 'FrCATTCGTG CATccTfrCT GATTCCTCTT ACCTTGCTAA AAGGAGAAGT TGMGGGT ATCCTATATC AATGGCAGGA AGGTTG'TM CTTCnI7ACC TPATCCTAT AGATTCATAT TCTCAACACC AACCTCCTCC TI=CAG'rr TCCTTCTI7GC TI1CTCTI'GAC ACCACAGAGT 'ITGCAGCTAG TACTTGGAGA GGAAAATTAA ACAGAGATAC TTGGACCAAG AGTAAGATGA AGAAAGTCTA AACAACAGTA TAGTCTATAG TGGCAAGAGA GAGTATGGGG GCTGCTTAGC CAGGGTGGCT GTACATAAAG TATATCTTCA 15 GTATATAA ACTGCTTATA GATGGAAATC AGAAAAYTTA AAT7CTCTTA ACTGTCCAAG AAAATFCTCA TTTICAAA TITGGGACTG ATAAATGTGA CCAG'ITCTGC ITACTGTCCA TTGCCTGAAA TGGAGCTTTG AGGTGGACTG TATAATITTCT TCAATCTTAA CTCCAAA'ITC TGATCAGCGA CGCCCTCTGC TGTTCACTAT TAATATTTAT TTACCAATCA AAGTAAAGTA TTGAAGTIT CCTGGCAGTT T7CACTIT7GT GTTTTAGTCC ATTT1AGGCTG CTATAACAAA ATCCCTTAAA CTGGGTAAGG GATTATAAAT ATTAGAAATT TATCTCTCAC 20 AGTTCTGGAA GCTGGGAAGC CCAATATCAA GGCACCAGTA GATITGGTGT CTAACGAGGG TGTGCCGTCT GCT'CAAAAA TGGCCCCI17G TTGCTGCATC CTCACTTAGT GCAAGGGGCA AGACAGCTCC CTTCAACCTC TITTATAAGG GCACTJ'ATGT CATTCATGAG GGCAGAGCCC TCATGACTI'A ATCACTTCCC CAAAGGCCCC ACCTC'AAT AGTATCACAT TGGGTGTrAG GTGTCTGGGA GGACACCAAT CTCAAGCCA TATCATCTCA CTTGGAAAAA AGTCAAAATA AAACCAGTAG ATTTAATrAA TATTACACTA TrATAGAAG CATGTGATGT 25 ATCATCCfr GTATTAATTT CCTGGGGTFG CCGTAACAAG 'rrACCACAAA CTAGGTGGCT TAAAACAATA GAAT1TTATT CTCTCACATI' TCTAGAGGCA GAAGTTCACA GTGTGTCAAT AGGGCCATGT TCTCTGGAAG GC'TAGGGG AGAATATAT7 TCATATCTT CTCIrAGCM CTCGGTGTCA CTGGCAATCC TFAGCTTACT TTGGC'I=CT GTGTCTTCAC ATCATC7M11 TATAAGAACA CCAGTGATAG TGATFAAGGG CATACCTrAC TrAATATGA CCTCATCTI'A ACTAAYI'ATG TCTTrCAATAA CCCTAMTCC AAATAAGGCC ACATTCTGAA 30 GTATTGGGAG TTAGAACTTA AAGC T[G GGAGGGACAC AGTTICAACCC ATAACAACCC CTAAAATCGA TA'IMATTCT CAATTAAGTC TFGAAATTGG ITTTCAAAAAG AGAATATTCT ATTAGAGT~ 'ITAATGTATA GTITTAACAT ATAGTTCTTT AGCCCCCAAT TYITT= TTr1TTrr TfITflT TIFFGAGAC GGAGTCTCGC TCTGTCGCCC AGGCCGGACT GCGGACTGCA GTGGCGCAAT CTCGGCTCAC TGCAAGCTCC GCTTCCCGGG TICACGCCAT TCCCCTGCCT CAGCCTCCCG AGTAGCTGGG ACTACAGGCG CCTGCCACCG 35 CGCCCGGCTA A'TTT=GT ATflTAGTA GAGACGGGGT TTCACCTTGT TAGCCAGGAT GGTCTCGATC TCCTGACCTC ATGATCCACC CGCCTCGGCC TCCCAAAGTG CTGGGA'ITAC AGGCGTGAGC CACCGCGCCC GGCCTGCCCC CAATTATTTA GTFIICTAT AAACAGGGAA ATFTTA ITGT GTGGCCCTA GAACTAATTT AA'1TTCCACT CTAATTCCTA CTTATG'ITTA TATAATGCTT FrAGAAATr GT~ATTY'CA GAAAATAAAC ATATACTA FT GTATCTG'TG CCTACACTTA GATI1ATTG CCTGCTATAT TrAAA3TIA 'VrAGTATITTr 40 AATTGTTTTA TI'AAAGAAAG AATGTGCCTG TAATCTCAGC ACTITGAGA GGCCAAGGCA GAAGGA FrGC TTGAGCCCAG GAGTIGAGA CCAGACTGAG CAACACAGGG AGACCCCCAT CTCTACAAAA AATAAAAAAA 'JTCTCCAGGC CTCATGGCAC ATACCTGTAG YrCTAGTTAC TTGGGAGACT GGGGTGGGAG GATGCATTGA GCCCAGGAGA TTGAGGCTGC AGTGAGCCAT GATCAGGCCA CTGTACTCCA GC= GGACAA CAGAGTGAGA GCTTGTCTAG ATAGATAGAT AGATAGATAA TCTAAATAGA TAATAGACAG A'FrATCTAAA TAGATAATAG 45 ACAGA'ITATC TAAATAGATA ATAGACAGAT TATCTAAATA GATAATAGAC AGATI'ATCTA AATAGATAAT AGACAGATTA TCTAAATAGA TAATAGACAG AITrATCTATC TAAATAGATA ATAGATTATC TAAATAGATA ATAGATAGAT AGATTAGATA GATAGATAGA TAGATAGAGC TI7GGACAACA GAGTGAGAGC CTGTCTAGAT AGATAGAAAC AAAGAAAGAA AGAAAGAATG GTGCTCATAT TTAAAGCAT TGAAAAATGG TCTTCC FTGC TrATATrACC CACACC=CT 'ITGTFrGGCAT TAAGATGCAA ACTYGTMT AAACAGTTGA GTAAATCAAA 50 GATGGGACTG TTAAGTTATr TGTGTrA'Tr ACCTGC'II TGAAAATGTA AAAATAAAAC TCTAGGYL'A ATrAGTAGTA TGCTMTTTAG TAATGAAGTA AAGCTAGAGG CTTCGAACAA ATCTI'GTGTA A'PrCCTCTr GAATGAGAGA GAAAATI1'AA AGTAAGCAAA CAAATAAGTr GTGTGTCACC ACTCA17CAG TCA1T~AACA AGTATTTCCA GAGTACTTAT TCTGTGCCAG GAAATGTTGT AGGTGCCCTC AACAACTfTAG AGTCTAGCCT GAGACACAAG TAAGTAGGTA ATTA'ITATAG AATGGTATGA TCTTTGGAGG ACTGGGTATT GGCTGGCTCA 55 TGGGAGTACA AGATAGGTAC CCAGTGATGA AGTCAGGAAA GGTTTCTTAT GGTGATATGA TGACGTCTAT GCTGATFATA AGGTCAGTGT AGAATAAACT 1TGTGCTIT AAATITGCAT AGCACTGTAT TAGAGAGTrC ATCTTCAAAA TAATCGAAAA GGCTGAGTGT GGTGACCCAT GGCTGTAATC CCAGCACIr GGGAGGCCGA GGTGGGCAGA 'ITGCTTGAGC TAGGAGTTCG AGACCAGGCT GGCCAACATG GTGAAACCCC GTCTCTACTA AAAATACAAA AATTAGCCAG GAGTGATGGT GCGCACCTGT AATGCCAGCT ACTTGGGAGG CTGAGGCAGG 60 AGGATCACTT GAACCCAGGA GGTGGAGGTT GAAGTAAGCC GAGGTCATGC CACTGCACTC CAGCCTGGGC AACAGAGTGA GACTCCATCT CAAAAAAAAA AAAAATGATC AAAGAAAGGT GAATITTCAT CTACCCTAYT TCTGCTGAGG AAAATGGACT A3T=CAAAT ATITAATA AGGGTCAAAA TGAGGGATC-3' (FRAG.NO:_)(SEQ.ID NO:2480) 5'-CCTGAGACAG AGGCAGCAGT GATACCCACC TGAGAGATCC TGTGTT'TGAA CAACTGCTTC CCAAAACGGA 65 AAGTATCA AGCCTAAACC TTTGGGTGAA AAGAACTCTT GAAGTCATGA TTGCTTCACA GTTI'CTCTCA GCTCTCACT7 TGGTGCT-rCT CATI'AAAGAG AGTGGAGCCT GGTC1TACAA CACCTCCACG GAAGCTATGA CTTATGATGA GGCCAGTGCT TATF[GTCAGC AAAGGTACAC ACACCTGGT-r GCAATTCAAA ACAAAGAAGA GATTGAGTAC CTAAACTCCA TATTGAGCTA TrCACCAAGT TA'ITACTGGA -FGGAATCAG AAAAGTCAAC AATGTGTGGG TCTGGGTAGG AACCCAGAAA CCTCTGACAG AAGAAGCCAA GAACTGGGCT CCAGGTGAAC 70 CCAACAATAG GCAAAAAGAT GAGGACTGCG TGGAGATCTA CATCAAGAGA GAAAAAGATG TGGGCATGTG GAATGATGAG AGGTGCAGCA AGAAGAAGCT TGCCCTATGC TACACAGCTG CCTGTACCAA TACATCCTGC AGTGGCCACG GTGAATGTGT AGAGACCATC AATAA'ITACA C'ITGCAAGTG TGACCCTGGC TTCAGTGGAC WO 00/62736 PCT/US00/08020 206 TCAAGTGTGA GCAAATTGTG AACTGTACAG CCCTGGAATC CCCTGAGCAT GGAAGCCTGG TTTGCAGTCA CCCACTGGGA AACTTCAGCT ACAATTCTTC CTGCTCTATC AGCTGTGATA GGGGTTACCT GCCAAGCAGC ATGGAGACCA TGCAGTGTAT GTCCTCTGGA GAATGGAGTG CTCCTATTCC AGCCTGCAAT GTGGTTGAGT GTGATGCTGT GACAAATCCA GCCAATGGGT TCGTGGAATG TTCCAAAAC CCTGGAAGCT TCCCATGGAA 5 CACAACCTGT ACATTrGACT GTGAAGAAGG ATTTGAACTA ATGGGAGCCC AGAGCCTTCA GTGTACCTCA TCTGGGAATT GGGACAACGA GAAGCCAACG TGTAAAGCTG TGACATGCAG GGCCGTCCGC CAGCCTCAGA ATGGCTCTGT GAGGTGCAGC CATTCCCCTG CTGGAGAGTT CACCTTCAAA TCATCCTGCA ACTTCACCTG TGAGGAAGGC TTCATGTTGC AGGGACCAGC CCAGGTTGAA TGCACCACTC AAGGGCAGTG GACACAGCAA ATCCCAGTTT GTGAAGCTTT CCAGTGCACA GCCTTGTCCA ACCCCGAGCG AGGCTACATG AATTGTCTTC 10 CTAGTGCTTC TGGCAGTTTC CGTTATGGGT CCAGCTGTGA GTTCTCCTGT GAGCAGGGTT TTGTGTTGAA GGGATCCAAA AGGCTCCAAT GTGGCCCCAC AGGGGAGTGG GACAACGAGA AGCCCACATG TGAAGCTGTG AGATGCGATG CTGTCCACCA GCCCCCGAAG GGTTTGGTGA GGTGTGCTCA TTCCCCTATT GGAGAATTCA CCTACAAGTC CTCTTGTGCC TTCAGCTGTG AGGAGGGATT TGAATTATAT GGATCAACTC AACTTGAGTG CACATCTCAG GGACAATGGA CAGAAGAGGT TCCTTCCTGC CAAGTGGTAA AATGTTCAAG CCTGGCAGTT 15 CCGGGAAAGA TCAACATGAG CTGCAGTGGG GAGCCCGTGT TTGGCACTGT GTGCAAGTTC GCCTGTCCTG AAGGATGGAC GCTCAATGGC TCTGCAGCTC GGACATGTGG AGCCACAGGA CACTGGTCTG GCCTGCTACC TACCTGTGAA GCTCCCACTG AGTCCAACAT TCCCTTGGTA GCTGGACTT CTGCTGCTGG ACTCTCCCTC CTGACATTAG CACCATTTCT CCTCTGGCTT CGGAAATGCT TACGGAAAGC AAAGAAATTT GTTCCTGCCA GCAGCTGCCA AAGCCTTGAA TCAGACGGAA GCTACCAAAA GCCTTCTTAC ATCCTTTAAG TTCAAAAGAA 20 TCAGAAACAG GTGCATCTGG GGAACTAGAG GGATACACTG AAGTTAACAG AGACAGATAA CTCTCCTCGG GTCTCTGGCC CTTCTTGCCT ACTATGCCAG ATGCCTTAT GGCTGAAACC GCAACACCCA TCACCACTTC AATAGATCAA AGTCCAGCAG GCAAGGACGG CCTTCAACTG AAAAGACTCA GTGTTCCCTT TCCTACTCTC AGGATCAAGA AAGTGTTGGC TAATGAAGGG AAAGGATATT TTCTTCCAAG CAAAGGTGAA GAGACCAAGA CTCTGAAATC TCAGAATTCC TITTCTAACT CTCCCTTGCT CGCTGTAAAA TCTTGGCACA GAAACACAAT 25 ATTTTGTGGC IT TTCTT TTGCCCTTCA CAGTGTTTCG ACAGCTGATT ACACAGTTGC TGTCATAAGA ATGAATAATA ATTATCCAGA GTTTAGAGGA AAAAAATGAC TAAAAATATT ATAACTTAAA AAAATGACAG ATGTTGAATG CCCACAGGCA AATGCATGGA GGGTTGTTAA TGGTGCAAAT CCTACTGAAT GCTCTGTGCG AGGGTTACTA TGCACAATTT AATCACTTTC ATCCCTATGG GATTCAGTGC TTCTTAAAGA GTTCTTAAGG ATTGTGATAT TTTTACTTGC ATTGAATATA TTATAATCTT CCATACTTCT TCATTCAATA CAAGTGTGGT 30 AGGGACTTAA AAAACTTGTA AATGCTGTCA ACTATGATAT GGTAAAAGTT ACTTAT-TCTA GATTACCCCC TCATrGTTTA TTAACAAATT ATGTTACATC TGTTITAAAT TTATTTCAAA AAGGGAAACT ATTGTCCCCT AGCAAGGCAT GATGTTAACC AGAATAAAGT TCTGAGTGTT TTTACTACAG TITGTTTG AAAACATGGT AGAATTGGAG AGTAAAAACT GAATGGAAGG TTGTATATT GTCAGATATT TTTTCAGAAA TATGTGGTTT CCACGATGAA AAACTTCCAT GAGGCCAAAC GTTTTGAACT AATAAAAGCA TAAATGCAAA CACACAAAGG 35 TATAATTTA TGAATGTCTT TGTTGGAAAA GAATACAGAA AGATGGATGT GCTGCATT CCTACAAAGA TGTTTGTCAG ATGTGATATG TAAACATAAT TCTTGTATAT TATGGAAGAT TTTAAATTCA CAATAGAAAC TCACCATGTA AAAGAGTCAT CTGGTAGATT TTTAACGAAT GAAGATGTCT AATAGTTATT CCCTATTTGT TTCTTCTGT ATGTTAGGGT GCTCTGGAAG AGAGGAATGC CTGTGTGAGC AAGCATTrAT GATTTAT AAGCAGATTT AACAATTCCA AAGGAATCTC CAGTTCAG TTGATCACTG GCAATGAAAA ATTCTCAGTC 40 AGTAATTGCC AAAGCTGCTC TAGCCTTGAG GAGTGTGAGA ATCAAAACTC TCCTACACTT CCATTAACTT AGCATGTGTT GAAAAAAAAA GTTTCAGAGA AGTTCTGGCT GAACACTGGC AACGACAAAG CCAACAGTCA AAACAGAGAT GTGATAAGGA TCAGAACAGC AGAGGTTCTT TTAAAGGGGC AGAAAAACTC TGGGAAATAA GAGAGAACAA CTACTGTGAT CAGGCTATGT ATGGAATACA GTGTrA1T1 CTTGAAATT GTTTAAGTGT TGTAAATATT TATGTAAACT GCATTAGAAA TTAGCTGTGT GAAATACCAG TGTGGTTTGT GTTTGAGTTT 45 TATrGAGAAT TTTAAATTAT AACTTAAAAT ATTATAAT TITTAAAGTA TATATTTATT TAAGCTTATG TCAGACCTAT TTGACATAAC ACTATAAAGG TTGACAATAA ATGTGCTTAT GTTT-3'(FRAG.NO:_)(SEQ.ID NO:2479) 5'-CCT TGC CTG CTG G-3' (FRAG. NO: 1739) (SEQ. ID NO: 1752) 5'-GTT GTC CC-3' (FRAG. NO: 1740) (SEQ. ID NO:1753) 5'-GTT CT GGC TTC TTC TGT C-3' (FRAG. NO:1080) (SEQ. ID NO:1088) 50 5'-GGC TGG TGG-3' (FRAG. NO:1083) (SEQ. ID NO:1092) 5'-CGT TGG CTT CTC GTT GTC CC-3' (FRAG. NO:1081) (SEQ. ID NO:1089) 5'-TGT GGG CTT CTC GTT GTC CC-3' (FRAG. NO:1082) (SEQ. ID NO:1090) 5'-CCC TIC GGG GGC TGG TGG-3' (FRAG. NO:1083) (SEQ. ID NO:1091) 5'-GGC CGT CCT TGC CTG CTG G-3' (FRAG. NO:1084) (SEQ. ID NO:1093) 55 Human P Selectin Fragments 5'-TTT TCT CTT TCG CTT TCT TTT CGT CTC CTG TTC CTC CTT TT TTG CTG TTT TTT CTC CTT CTT CTC TCC TTT CTT TTC-3' (FRAG. NO: 1741) (SEQ. ID NO: 1754) 5'-TCC T CTT TTC-3' (FRAG. NO: 1742) (SEQ. ID NO: 1755)] 5'-CTC CTT TT-3' (FRAG. NO:1743) (SEQ. ID NO:1756) 60 5'-TTT TCT CTT TCG CTT TCT TTT CGT CTC CTG TTC CTC CTT TT-3'(FRAG.NO:1085)(SEQ. ID NO:1094) 5'-TTG CTG TTT TTT CTC CTT CTT CTC TCC TTT CTT TTC-3' (FRAG. NO:1086) (SEQ. ID NO:1095) Human Endothelial Monocyte Activating Factor Nucleic Acid & Antisense Oligonucleotide Fragments 5'-TTT TCT CTT TCG CTT TCT TTT CGT CTC CTG TTC CTC CTT TT TTG CTG TT TT CTC CTT CTT CTC WO 00/62736 207 PCT/USOO/08020 TCC TTT CTT TTC-3' (FRAG. NO: 1744) (SEQ. ID NO: 1757) S' -CC TTT CTT TTC (FRAG. NO: 1745) (SEQ. ID NO: 1758) 5'-CTG TTC CTC CTT TT-3' (FRAG. NO:1746) (SEQ. ID NO:1759) 5'-TTT TCT CTT TCG CTT TCT TTT CGT CTC CTG TTC CTC CTT TT-3'(FRAG.NO:1087)(SEQ. ID NO:1096) 5 5'-TTG CTG TTT TTT CTC CTT CTT CTC TCC TTT CTT TC-3' (FRAG. NO:1088) (SEQ. ID NO:1097) Human IL3* Nucleic Acid and Antisense Oligonucleotide Fragments 5'-CTC TGT CTT GTT CTG GTC CTT CGT GGG GCT CTG TGT CGC GTG G GTG CGG CCG TGG CC GGC GGB CCB GGB GTT GGB GCB GGB GCB GGB CGG GCB GGC GGC TCB TGT TTG GBT CGG CBG GBG GCB CTC (FRAG. NO: 1747) (SEQ. ID NO: 1760)] 10 5'-G GBG GCB CTC-3' (FRAG. NO: 1748) (SEQ. ID NO: 1761) 5'-GT GGG GCT CTG-3' (FRAG. NO:1749) (SEQ. ID NO:1762) HUMIL3AAS1: 5'-CTC TGT CTT GTT CTG GTC CTT CGT GGG GCT CTG-3' (FRAG.NO:1089)(SEQ.ID NO:1098) HUMIL3AAS2: 5'-TGT CGC GTG G GTG CGG CCG TGG CC-3' (FRAG. NO:1090) (SEQ. ID NO:1099) GGC GGB CCB GGB GTT GGB GCB GGB GCB GGB CGG GCB GGC GGC TCB TGT TTG GBT CGG CBG GBG GCB 15 CTC (FRAG. NO:1091) (SEQ. ID NO:1100) Human IL3 Receptor Nucleic Acid and Antisense Oligonucleotide Fragments 5'-TCT GGG GTG TCC TGG CCT TCG TGG TTC CTC TTC CTU CGT TTG CCG TCC GCG GGG GCC CCC GGG CCT GGC TGC GCT CCT GCC CCG CCT CTT TCC CGG GCT CTT GCG CTG GGG GGT GCT CC CGT GTG TTT GCG CCC TC CTC CTG GTC GCG CTT GTC GTT TTG GGG CCG GCT TTG CCC GCC TCC CGG CGC CTG GCC 20 CGG CC TTC CTG GGC TGC GTG CGC GTT CTG TC TTC TTC CTG GCT CTG GGG TGT CCT GGC CTU CGT GGT TCC TCT TCC TTC GTT TGC CGT CCG CGG GGG CCC CCG GGC CT GGC TGC GCT CCT GCC CCG CCT CTU TCC CGG GCT CU GCG CTG GGG GGT GCT CCC GTG TGT TTG CGC CCT CCT CCT GGT CGC GCT TGT CGT T] GG GGC CGG CTT TGC CCG CCT CCC GGC GCC TGG CCC GGC CTT CCT GGG CTG CGT GCG CGT TCT GTT CTT CTT CCT GGC GCA GGA GAC AGG GCA GGG CGA TCA GGA GCA GCG TGA GCC AAA GGA 25 GGA CCA TCG GGA ACG CAG CTC CGG AAC GCA GGA CAG AGG TGC C GC BGG BGB CBG GGC BGG GCG BTC BGG BGC BGC GTG BGC CBB BGG BGG BCC BTC GGG BBC GCB GCT CCG GBB CGC BGG BCB GBG GTG CC-3' (FRAG. NO: 1750) (SEQ. ID NO: 1763) GBG GTG CC-3' (FRAG. NO: 1751) (SEQ. ID NO: 1764) 5'- GCC CCG C-3' (FRAG. NO:1752) (SEQ. ID NO:1765) 30 5'-TCTGGGGTGTCCTG (FRAG. NO:1092) (SEQ. ID NO:1101) 5'-GCCTCGTGGTCC (FRAG. NO:1093) (SEQ. ID NO:1102) 5'-TCTTCCTTCGTTTGC (FRAG. NO:1094) (SEQ. ID NO:1103) 5'-CGTCCGCGGGGGCCCCCGGGCCT (FRAG. NO:1095) (SEQ. ID NO:1105) 5'-GGC TGC GCT CCT GCC CCG C (FRAG. NO:1096) (SEQ. ID NO:1104) 35 5'-CTCTTTCCCGGGCTCTT (FRAG. NO:1097) (SEQ. ID NO:1106) 5'-GCGCTGGGGGGTGCTCC (FRAG. NO:1098) (SEQ. ID NO:1107) 5'-CGTOTGTIGCGCCCTCCTCCTGGTCGC (FRAG. NO:1099) (SEQ. ID NO:1108) 5'-GCTTGTCGTTGG (FRAG. NO:1100) (SEQ. ID NO:1109) 5'-GGCCGGCTTTGCCCGCCTCCC (FRAG. NO:1101) (SEQ. ID NO:1110) 40 5'-GGCGCCTGGCCCGGCC (FRAG. NO:1102) (SEQ. ID NO:1111) 5'-TTCCTGGGCTGCGTGCGC (FRAG. NO:1103) (SEQ. ID NO:1112) 5'-GTTCTGTTCTCCCTGGC (FRAG. NO:1104) (SEQ. ID NO:1113) 5'-GCB GGB GBC BGG GCB GGG CGB TCB GGB GCB GCG TGB GCC BBB GGB GGB CCB TCG GGB BCG CBG CTC CGG BBC GCB GGB 5'-CBG BGG TGC C (FRAG. NO:1105) (SEQ. ID NO:1114) 45 Human IL-4 Nucleic Acid and Antisense Oligonucleotide Fragments 5'-CTC TGG TTG GCT TCC TTC GCC GGC BCB TGC TBG CBG GBB GBB CBG BGG GGG BBG CBG TTG GGB GGT GBG BCC CBT TBB TBG GTG TCG B-3' (FRAG. NO: 1753) (SEQ. ID NO: 1766) 5'-GCC GGC BCB-3' (FRAG. NO: 1754) (SEQ. ID NO: 1767) 5'-T TCC TTC-3' (FRAG. NO:1755) (SEQ. ID NO:1768) 50 5'-CTC TGG TTG GCT TCC TTC-3' (FRAG. NO:1106) (SEQ. ID NO:1115) 5'-GCCGGCBCBTGCTBGCBGGBBGBBCBGBGGGGGBBGCBGTTGGGBGGTGBGBCCCBTTBBTBGGTGTCGB-3' (FRAG. NO:1107) (SEQ. ID NO:1116) Human IL4 Receptor Nucleic Acid and Antisense Oligonucleotide Fragment 5'-TCT GCC CTG TCC GCC GGC TCT TCG GTG GCT CGG CCC CGC TCC TTG TCT TGC CGC GGG TTG GTT 55 CCT GGG CCT GGT TCT TGC GGG CGT TTC GGT CTG CTG GCT GGT CTG GGC CCG CGG TGC GGC GGG TGG CTT GCT GTT CTG CCT GGG CTC TCC CCT CTC CTC CTT TTC TCC CTU CCT CTG TCT TGC CTC CTT CCT CTG GGT CCT CTT GGC CTG GGC GCT CTT CCC CTC GGG CGG CTG CGG GCG CTC GTG CTG CCT GGT CCG CTC CCT GGG GGT GCT CCT TCC CTT TCC CCG CTC GTG GGG TTT GCG GGG CTG GGC TGC CCT GGG GGG TCT GGG CCT TTT GGG GTC GGC TGG CTG CTG CTT CGG GCC GCC TGG GCT TCC CTG TGC CCC TTT CCT 60 CTG CTG GGT CCC CCT CCC GTT CCA AGC TGC ACC GCA CAG ACC GGC GCT ACA GGA CAG AGC CAG GCA AGC ACC CAT GGG GAT CCA GGC CCA GCT GTT CCB BGC TGC BCC GCB CBG BCC GGC GCT BCB GGB CBG BGC CBG GCB BGC BCC CBT GGG GBT CCB GGC CCB GCT G -3'(FRAG. NO: 1756)(SEQ ID NO:1769) 5'-TCTGCGC-3' (FRAG. NO: 1757) (SEQ ID NO: 1770) WO 00/62736 PCT/USOO/08020 208 5'-CCT GCT CCT GGG G (FRAG. NO:1758) (SEQ. ID NO:1771) 5'-TCTGCGCGCCCCTGCTCC (FRAG. NO:1108) (SEQ. ID NO:1117) 5'-CGCCCGGCTTCTCT (FRAG. NO:1109) (SEQ. ID NO:1118) 5'-CGTGTGGGCTTCGG (FRAG. NO:1110) (SEQ. ID NO:1119) 5 5'-CCCCGCGCCTCCGTTGTTCTC (FRAG. NO:1111) (SEQ. ID NO:1120) 5'-TGCTCGCTGGGCT'TG (FRAG. NO:1112) (SEQ. ID NO:1121) 5'-GGT'TTCCTGGGGCCCTGGGTTTC (FRAG. NO:1113) (SEQ. ID NO:1122) 5'-TCTGCCGGGTCGTTTTC (FRAG. NO:1114) (SEQ. ID NO:1123) 5'-GGGTGCTGGCTGCG (FRAG. NO:1115) (SEQ. ID NO:1124) 10 5'-CTTGGTGCTGGGGCTCC (FRAG. NO:1116) (SEQ. ID NO:1125) 5'-GGCGGCTGCGGGCTGGGTTGGG (FRAG. NO:1117) (SEQ. ID NO:1126) 5'-CTTGGCTGGTTCCTGGCCTCGGG (FRAG. NO:1118) (SEQ. ID NO:1127) 5'-CCTCCTCCTCCTCCTCGCTCCCTTTTTCTTCCTCT (FRAG. NO:1119) (SEQ. ID NO:1128) 5'-TCCCTGCTGCTCTC (FRAG. NO:1120) (SEQ. ID NO:1129) 15 5'-TGCCCTCCCTTCCCTCCTGG (FRAG. NO:1121) (SEQ. ID NO:1130) 5'-GGTGCCTCCTTGGGCCCTGC (FRAG. NO:1122) (SEQ. ID NO:1131) 5'-GGCTGCTCCTTGCCCC (FRAG. NO:1123) (SEQ. ID NO:1132) 5'-CTCTGGGTCGGGCTGGC (FRAG. NO:1124) (SEQ. ID NO:1133) 5'-GGGGCGTCTCTGTGC (FRAG. NO:1125) (SEQ. ID NO:1134) 20 5'-CTGGCCTGGGTGCC (FRAG. NO:1126) (SEQ. ID NO:1135) 5'-GCCTCTCCTGGGGGGGTGGCTCCCTGTCC (FRAG. NO:1127) (SEQ. ID NO:1136) 5'-CCTTTTCCCCCGGCTCC (FRAG. NO:1128) (SEQ. ID NO:1137) 5'-GTGGGGGCTTTGGC (FRAG. NO:1129) (SEQ. ID NO:1138) 5'-GGG GGT CTG TGG CCT GCT CCT GGG G (FRAG. NO:1130) (SEQ. ID NO:1139) 25 5'-AGGGGTCTGGGGCCCTC (FRAG. NO:1131) (SEQ. ID NO:1140) 5'-TTTTGGGGGTCTGGCTTrG (FRAG. NO:1132) (SEQ. ID NO:1141) 5'-GCCTGGCTGCCTTCC (FRAG. NO:1133) (SEQ. ID NO:1142) 5'-GGGGCCTGCCGTGGGGC (FRAG. NO:1134) (SEQ. ID NO:1143) 5'-TGTCCTCTGTTGCTCCCCTT (FRAG. NO:1135) (SEQ. ID NO:1144) 30 5'-TGCCTGCTGTCTGG (FRAG. NO:1136) (SEQ. ID NO:1145) 5'-GGTTCCCGCCTTCCCT (FRAG. NO:1137) (SEQ. ID NO:1146) 5'-GTT CCC AGA GCT TGC CAC CTG CAG CAG GAC CAG GCA GCT CAC AGG GAA CAG GAG CCC AGA GCA AAG CCA CCC CAT TGG GAG ATG CCA AGG CAC CAG GCT G (FRAG. NO:1138) (SEQ. ID NO:1147) 5'-GTT CCC BGB GCT TGC CBC CTG CBG CBG GBC CBG GCB GCT CBC BGG GBB CBG GBG CCC BGB GCB BBG 35 CCB CCC CBT TGG GBG BTG CCB BGG CBC CBG GCT G-3' (FRAG. NO:1139) (SEQ. ID NO:1148) Human ILS* Nucleic Acid and Antisense Oligonucleotide Fragments 5'-TCCCTGTTTC CCCCCTTTCG TTCTGCGTTT GCCTTTGGCG TTTTTTGTTT GTTTTCTCTC TCCGTCTITC TTCTCCCCT GTGGGBBTTT CTGTGGGGBT GGCBTBCBCG TBGGCBGCTC CBBGBGCTBG CBBBCTCBBB TGCBGBBGCB TCCTCBTGGC TCTGBBBCGG TGGGAATTTC TGTGGGGBTG GCATACACGT AGGCAGCTCC 40 AAGAGCTAGC AAACTCAAAT GCAGAAGCATC CTCATGGCTC TGAAACG-3' (FRAG. NO: 1759) (SEQ. ID NO: 1772) 5'-GCC CCG GG-3' (FRAG. NO: 1760) (SEQ. ID NO: 1773) 5'-G GGT TTC T-3' (FRAG. NO: 1761) (SEQ. ID NO: 1774) 5'-GTG GGG BTG GC-3' (FRAG. NO: 1762) (SEQ. ID NO:1775) 45 5'-CCB BGB GCT BGC-3' (FRAG. NO: 1763) (SEQ. ID NO: 1776) 5'-TCC CTG TTT CCC CCC TTT-3' (FRAG. NO:1140) (SEQ. ID NO:1149) 5'-CGT TCT GCG TTT GCC TTT GGC-3' (FRAG. NO:1141)(SEQ. ID NO:1150) 5'-GTT TTT TGT TTG TTT TCT-3' (FRAG. NO:1142)(SEQ. ID NO:1151) 5'-CTC TCC GTC TTT CTT CTC C-3' (FRAG. NO:1143) (SEQ. ID NO:1152) 50 5'-CCT CCT GCC TGT GTC CCT GCT CCC C-3' (FRAG. NO:1144) (SEQ. ID NO:1153) 5'-GAG GGT TTC TGG CTT CCT CTC T-3' (FRAG. NO:1145) (SEQ. ID NO:1154) 5'-TGT CTC TCT GTC CTT TTG TT-3' (FRAG. NO:1146) (SEQ. ID NO:1155) 5'-TGT TGT GCG GCC TGG TGC TGC CCT GCC CCG GG-3' (FRAG. NO:1147) (SEQ. ID NO:1156) 5'-GTG GGA ATT TCT GTG GGG BTG GCA TAC ACG TAG GCA GCT CCA AGA GCT AGC AAA CTC AAA TGC 55 AGA AGC ATC CTC ATG GCT CTG AAA CG-3' (FRAG. NO: 1764) (SEQ. ID NO: 1777) 5'-GTG GGB BTT TCT GTG GGG BTG GCB TBC BCG TBG GCB GCT CCB BGB GCT BGC BBB CTC BBB TGC BGB BGC BTC CTC BTG GCT CTG BBB CG-3' (FRAG. NO:1148) (SEQ. ID NO:1157) Human IL-5 Receptor Nucleic Acid and Antisense Oligonucleotide Fragments 5'-CTCAGTGGCC CCCAAAAGGA TGAGTAATAC ATGCGCCACG ATGATCATAT CCTTTTTACT ATGAGGCCGT 60 GTCTGTCGTG TCTTTCCTT GCTCTTGGTG TGTCTTTGCT GTGCCCTGCC TCTCTGCCCG TGTCTGTCGT GTCTTTCCTT TGCTCTTGGT GTGTCTTTGC TGTGCCCTGC CTCTCTGCC CGTGTCTGTC GTGTCTTTCC TTTGCTCTTG GTGTGTCTTT GCTGTGCCCT GCCTCTCTGC-3' (FRAG. NO: 1765) (SEQ. ID NO: 1778) 5'-CCG TGT C-3' (FRAG. NO: 1766) (SEQ. ID NO: 1779) 5'-GCCCTGCC-3' (FRAG. NO: 1767) (SEQ. ID NO: 1780) 65 5'-CCG TGT CTG TCG TGT CT-3' (FRAG. NO:1149) (SEQ. ID NO:1158) WO 00/62736 PCT/USOO/08020 209 5'-TTCCTTTGCTCTTG-3' (FRAG. NO:1150) (SEQ. ID NO:1159) 5'-GTGTGTCTTTIGCTGT-3' (FRAG. NO:1151) (SEQ. ID NO:1160) 5'-GCCCTGCCTCTCTGC-3' (FRAG. NO:1152) (SEQ. ID NO:1161) 5'-CT CBGTGGCCCC CBBBBGGBTG BGTBBTBCBT GCGCCBCGBT GBTCBTBTCC TTTTBCTBT GBGG (FRAG. 5 NO: 1768) (SEQ. ID NO: 1781) Human IL-6 Receptor Fragments 5'-GGGGGTGGCT TCCTGCCGCG TCTCTGGGCC GTCCCGTCCC TCGGCCCCGC GCCGCGCTCG GCTCCTCTCC CTCTGGCCCG GCTCGGGGCG GGGCGGGGCG GTGGGCGGGC GGCGCTGCCC TGCGCGCGGC GCTGGCCCCT GCTGGCCGTC GGCTGCGCGC TGCTGGCTGC CCTGCTGGCC GCGCCGGGGC CTGTCCGCCT CTGCGGGCGC 10 TGTCTCCTGG CTTGTCTTCC GGCTCTTCTG CTGGGGTGGG GCTGGGCGGC CGGCCCGGTG CTGGGGCTCC TCGGGGGGGG GGGCTCTTCC GGGCTGTCTC CCTCCGGGGC GGGGGTTTCT GGCCGTGGGG GTCTTGCCTG GCCTCCGGGC TCCTGCTTGT CTTGCCTTCC TTCTCTGGTC GGTTGTGGCT CGGGGCTCCG TGGGTCCCTG GCGCCCGTTT GTGTTTTGTC TTTTCCCCTG GCGTCCCTGT GCCCCTCTCC TCTCCTTCCT CTGCTTCTCG CTCTCCTTG TGGGGCCCTC CCTGCTGCTC TTGGTTTGG GCTTTTTC TCTTCCTCCT TTTTCGTGCG 15 TGGGCCTCCG CACGCCTCTT GCCACCTCCT GCGCAGGGCA GCGCCTTGG GGCCAGCGCC GCTCCCGGCG CGGCCAGCAG GGCAGCCAGC AGCGCGCAGC CGACGGCCAG CATGCTTCCT CCTCGGCTAC CACTCCATGG TCCCGCAGAG GCGGACAGGC GCBCGCCTC TTGCCBCCTC CTGCGCBGGG CBGCGCCTTG GGGCCBGCGC CGCTCCCGGC GCGGCCBGCB GGGCBGCCBG CBGCGCGCBG CCGBCGGCCB GCBTGCTTCC TCCTCGGCTB CCBCTCCBTG GTCCCGCBGB GGCGGBCBGG C-3' (FRAG. NO: 1769) (SEQ. ID NO: 1782) 20 5'-CCCGGCGC-3' (FRAG. NO:1184) (SEQ. ID NO:1193) 5'-GGCCBGCBGG-3' (FRAG. NO:1186) (SEQ. ID NO:1195) 5'-GCBGCCBGCBGCG-3' (FRAG. NO: 1770) (SEQ. ID NO: 1783) 5'-C GCBGCCGBCGGCC -3' (FRAG. NO: 1771) (SEQ. ID NO: 1784) 5'-GGGGGTGGCTTCCTGCC3'- (FRAG. NO:1153) (SEQ. ID NO:1162) 25 5'-GCGTCTCTGGGCCGTCCC-3' (FRAG. NO:1154) (SEQ. ID NO:1163) 5'-GTCCCTCGGCCCCGCGCCGCGCTCGGCTCCTCTCCC-3' (FRAG. NO:1155) (SEQ. ID NO:1164) 5'-TCTGGCCCGGCTC-3' (FRAG. NO:1156) (SEQ. ID NO:1165) 5'-GGGGCGGGGCGGGGCGGTGGGCGGGC-3' (FRAG. NO:1157) (SEQ. ID NO:1166) 5'-GGCGCTGCCCTGCGC-3' (FRAG. NO:1158) (SEQ. ID NO:1167) 30 5'-GCGGCGCTGGCCCC-3' (FRAG. NO:1159) (SEQ. ID NO:1168) 5'-TGCTGGCCGTCGGCTGCGCGCTGCTGGCTGCCCT-3' (FRAG. NO:1160) (SEQ. ID NO:1169) 5'-GCTGGCCGCGCCGGG-3' (FRAG. NO:1161) (SEQ. ID NO:1170) 5'-GCCTGTCCGCCTCTGCGGG-3' (FRAG. NO:1162) (SEQ. ID NO:1171) 5'-CGCTGTCTCCTGGC-3' (FRAG. NO:1163) (SEQ. ID NO:1172) 35 5'-TTGTCTTCCGGCTCT-3' (FRAG. NO:1164) (SEQ. ID NO:1173) 5'-TCTGCTGGGGTGGG-3' (FRAG. NO:1165) (SEQ. ID NO:1174) 5'-GCTGGGCGGCCGGCCCGGT-3' (FRAG. NO:1166) (SEQ. ID NO:1175) 5'-GCTGGGGCTCCTCGGGGGG-3' (FRAG. NO:1167) (SEQ. ID NO:1176) 5'-GGGGGCTCTTCCGG-3' (FRAG. NO:1168) (SEQ. ID NO:1177) 40 5'-GCTGTCTCCCTCCGGG-3' (FRAG. NO:1169) (SEQ. ID NO:1178) 5'-GCGGGGGTTTCTGGCC-3' (FRAG. NO:1170) (SEQ. ID NO:1179) 5'-GTGGGGGTCTTGCC-3' (FRAG. NO:1171) (SEQ. ID NO:1180) 5'-TGGCCTCCGGGCTCC-3' (FRAG. NO:1172) (SEQ. ID NO:1181) 5'-TGCTTGTCTTGCCTTCCTTC-3' (FRAG. NO:1173) (SEQ. ID NO:1182) 45 5'-TCTGGTCGGTTGTGGCTCG-3' (FRAG. NO:1174) (SEQ. ID NO:1183) 5'-GGGCTCCGTGGGTCCCTGGC-3' (FRAG. NO:1175) (SEQ. ID NO:1184) 5'-GCCCGTTTGTGTTTTGTC-3' (FRAG. NO:1176) (SEQ. ID NO:1185) 5'-TTCCCCTGGCGT-3' (FRAG. NO:1177) (SEQ. ID NO:1186) 5'-CCCTGTGCCCCTCTCCTCTCCTTCCTCTGCTTCTC-3' (FRAG. NO:1178) (SEQ. ID NO:1187) 50 5'-GCTCTCCTTTGTGGG-3' (FRAG. NO:1179) (SEQ. ID NO:1188) 5'-GCCCTCCCTGCTGCT-3' (FRAG. NO:1180) (SEQ. ID NO:1189) 5'-CTTGGTTTGGGCT-3' (FRAG. NO:1181) (SEQ. ID NO:1190) 5'-TTTTTTCTCTTCCTCCTTTTTC-3' (FRAG. NO:1182) (SEQ. ID NO:1191) 5'-GTGCGTGGGCCTCC-3' (FRAG. NO:1183) (SEQ. ID NO:1192) 55 5'-GCACGCCTCT TGCCACCTCC TGCGCAGGGC AGCGCCTTGG GGCCAGCGCC GCTCCCGGCG CGGCCAGCAG GGCAGCCAGC AGCGCGCAGC CGACGGCCAG CATGCTTCCT CCTCGGCTAC CACTCCATGG TCCCGCAGAG GCGGACAGGC-3' (FRAG. NO:1185) (SEQ. ID NO:1194) 5'-GCBCGCCTCT TGCCBCCTCC TGCGCBGGGC BGCGCCTTGG GGCCBGCGCC GCTCCCGGCG CGGCCBGCBG GGCBGCCBG CBGCGCGCBG CCGBCGGCCB GCBTGCTTCC TCCTCGGCTB CCBCTCCBTG GTCCCGCBGB 60 GGCGGBCBGG C-3' (FRAG. NO:1187) (SEQ. ID NO:1196) Human IL-6 Nucleic Acid and Antisense Oligonucleotide Fragments 5'--GGGGGTGGCT TCCTGCCGCG TCTCTGGGCC GTCCCGTCCC TCGGCCCCGC GCCGCGCTCG GCTCCTCTCC CTCTGGCCCG GCTCGGGGCG GGGCGGGGCG GTGGGCGGGC GGCGCTGCCC TGCGCGCGGC GCTGGCCCCT GCTGGCCGTC GGCTGCGCGC TGCTGGCTGC CCTGCTGGCC GCGCCGGGGC CTGTCCGCCT CTGCGGGCGC 65 TGTCTCCTGG CTTGTCTTCC GGCTCTTCTG CTGGGGTGGG GCTGGGCGGC CGGCCCGGTG CTGGGGCTCC WO 00/62736 PCT/USOO/08020 210 TCGGGGGGGG GGGCTCTTCC GGGCTGTCTC CCTCCGGGGC GGGGGTTCT GGCCGTGGGG GTCTTGCCTG GCCTCCGGGC TCCTGCTTGT CTTGCCTTCC TTCTCTGGTC GGTTGTGGCT CGGGGCTCCG TGGGTCCCTG GCGCCCGTTT GTGTTGTC TTCCCCTG GCGTCCCTGT GCCCCTCTCC TCTCCTTCCT CTGCTTCTCG CTCTCCTTTG TGGGGCCCTC CCTGCTGCTC TTGGTTGG GCTTTTTC TCTTCCTCCT TTTTCGTGCG 5 TGGGCCTCC GCACGCCTCT TGCCACCTCC TGCGCAGGGC AGCGCCTTGG GGCCAGCGCC GCTCCCGGCG CGGCCAGCAG GGCAGCCAGC AGCGCGCAGC CGACGGCCAG CATGCTTCCT CCTCGGCTAC CACTCCATGG TCCCGCAGAG GCGGACAGGC GCBCGCCTC TTGCCBCCTC CTGCGCBGGG CBGCGCCTTG GGGCCBGCGC CGCTCCCGGC GCGGCCBGCB GGGCBGCCBG CBGCGCGCBG CCGBCGGCCB GCBTGCTTCC TCCTCGGCTB CCBCTCCBTG GTCCCGCBGB GGCGGBCBGG C-3' (FRAG. NO:1772) (SEQ. ID NO:1785) 10 5'-GGGGCBGG-3' (FRAG. NO:1773) (SEQ. ID NO:1786) 5'-GBBGGCBG CBGGC-3' (FRAG. NO:1774) (SEQ. ID NO:1787) 5'-CCBGGBGCBG CCCC-3' (FRAG. NO:1775) (SEQ. ID NO:1788) 5'-BGGG BGBBGGCBBC-3' (FRAG. NO:1776) (SEQ. ID NO:1789) 5'-GCT TCT CTT TCG TTC CCG GTG GGC TCG-3' (FRAG. NO:1188) (SEQ. ID NO:1197) 15 5'-GTG GCT GTC TGT GTG GGG CGG CT-3' (FRAG. NO:1189) (SEQ. ID NO:1198) 5'-GTG CCT CTT TGC TGC TTT C-3' (FRAG. NO:1190) (SEQ. ID NO:1199) 5'-GAT TCT TTG CCT TTT TCT GC-3' (FRAG. NO:1191) (SEQ. ID NO:1200) 5'-CTCCTGGGGG TBCTGGGGCB GGGBBGGCBG CBGGCBBCBC CBGGBGCBGC CCCBGGGBGB BGGCBBCTGG BCCGBBGGCG CTTGTGGBGB BGGBGTTCBT BGCTGGGCTC CTGGBGGGGB GBTBGBGC-3'(FRAG..NO:1777)(SEQ.ID NO:1790) 20 Human Monocyte-derived Neutrophil Chemotactic Factor Nucleic Acid and Antisense Oligonucleotide Fragments 5'-GGGGTGGBBB GGTTTGGBGT BTGTCTTTBT GCBCTGBCBT CTBBGTTCTT TBGCBCTCCT TGGCBBBBCT GCBCCTTCBC BCBGBGCTGC BGBBBTCBGG BBGGCTGCCB BGBGBGCCBC GGCCBGCTrG GBBGTCBTGT TTBCBCBCBG TGBGBTGGTT CCTTCCGGGC TrGTGTGCTC TGCTGTCTCT TGGTTCCTTC CGGTGGTTTC 25 TTCCTGGCTC TTGTCCTTTC TCTTGG CCCT TGGC-3' (FRAG. NO:1778) (SEQ. ID NO: 1791) 5'-GGBGT BTG-3' (FRAG. NO:1779) (SEQ. ID NO: 1792) 5'-GCBCTGBCBT CT-3' (FRAG. NO:1780) (SEQ. ID NO:1793) 5'-CCG GTG G-3' (FRAG. NO:1781) (SEQ. ID NO: 1794) 5'-GG CCC TTG GC-3' (FRAG. NO:1782) (SEQ. ID NO: 1795) 30 5'-GCT TGT GTG CTC TGC TGT CTC T-3' (FRAG. NO:1192) (SEQ. ID NO:1201) 5'-TGG TTC CTT CCG GTG GTT TCT TCC TGG CTC TG TCC T-3' (FRAG. NO:1193) (SEQ. ID NO:1202) 5'-TTC TCT TGG CCC TTG GC-3' (FRAG. NO:1194) (SEQ. ID NO:1203) 5'-GGGGTGGBBB GGTTTGGBGT BTGTCTTTBT GCBCTGBCBT CTBBGTTCTT TBGCBCTCCT TGGCBBBBCT GCBCCTTCBC BCBGBGC-3' (FRAG. NO:1783) (SEQ. ID NO: 1796) 35 Human Neutrophil Elastase (Medullasin) Nucleic Acid and Antisense Oligonucleotide Fragments 5'-GGGCTCCCGC CGCGBGBGGT TBTGGGCTCC CBGGBCCBCC CGCBCCGCGC GGBCGTTTBC BITCGCCBCG CBGTGCGCGG CCGBCBTGBC GBBGTTGGGC GCBBTCBGGG TGGCGCCGCB GBBGTGGCCT CCGCGCBGCT GCBGGGBCBC CBTGBBGGGC CBCGCGTGGG GCCGCGCTCG CCGGCCCCCC BCBBTCTCCG BGGCCBGCGC GGTGCCCCCC BGCBGCBBGG CCGGCBGGBC BCBGGCGBGG BGBCBCGCGB GTCGGCGGCC GBGGGTCBTG 40 GTGGGGCTGG GGCTCCGGGG TCTCTGCCCC TCCGTGCTGG TGGGGCTGGG GCTCCGGGG TCTCTGCCCC TCCGTGCCGC GTGGGGCCGC GCTCGCCGGC CCCCCCCTGC CGGGTGGGCT CCCGCCGCGC GCCGGCCTGC CGGCCCCTCG TGGGTCCTGC TGGCCGGGTC CGGGTCCCGG GGGTGGGGCG CGBGTCGGCG GCCGBGGGTC-3' (FRAG. NO:1784) (SEQ. ID NO: 1797) 5'-GG TGG GGC-3' (FRAG. NO:1785) (SEQ. ID NO: 1798) 45 5'-G GGG CCG -3' (FRAG. NO:1786) (SEQ. ID NO:1799) 5'- GGC CGG GTC CGG G-3' (FRAG. NO:1787) (SEQ. ID NO: 1800) 5'-TGG TGG GGC TGG GGC TCC GGG GTC TCT GCC CCT CCG TGC-3' (FRAG.NO:1195)(SEQ.ID NO:1204) 5'-CGC GTG GGG CCG CGC TCG CCG GCC CCC C-3' (FRAG. NO:1196) (SEQ. ID NO:1205) 5'-CCT GCC GGG TGG GCT CCC GCC GCG-3' (FRAG. NO:1197) (SEQ. ID NO:1206) 50 5'-CGC CGG CCT GCC GGC CCC TC-3' (FRAG. NO:1198) (SEQ. ID NO:1207) 5'-GTG GGT CCT GCT GGC CGG GTC CGG GTC CCG GGG GTG GGG-3'(FRAG.NO:1199)(SEQ.ID NO:1208) 5'-CGC GBG TCG GCG GCC GBG GGT C-3' (FRAG. NO:1200) (SEQ. ID NO:1209) 5'-GGGCTCCCGC CGCGBGBGGT TBTGGGCTCC CBGGBCCBCC CGCBCCGCGC GGBCGT'TTBC BTTCGCCBCG CBGTGCGCGG CCGBCBTGBC GBBGTTGGGC GCBBTCBGGG TGGCGCCGCB GBBGTGGCCT CCGCGCBGCT 55 GCBGGGBCBC CBTGBBGGGC CBCGCGTGGG GCCGCGCTCG CCGGCCCCCC BCBBTCTCCG BGGCCBGCGC GGTGCCCCCC BGCBGCBBGG CCGGCBGGBC BCBGGCGBGG BGBCBCGCGB GTCGGCGGCC GBGGGTCBTG GTGGGGCTGG GGCTCCGGGG TCTCTGCCCC TCCGTGC-3' (FRAG. NO:1788) (SEQ. ID NO: 1801) Human Neutrophil Oxidase Factor Nucleic Acid and Antisense Oligonucleotide Fragments 5'-CGGGBGTGGG GGTCCTGGBC GGCBCTGBBG GCBTCCBGGG CTCCCTTCCB GTCCTTCTTG TCCGCTGCCB 60 GCBCCCCTTC BTTCCBGBGG CTGBTGGCCT CCBCCBGGGB CBTGBTTBGG TBGBBBCTBG GBGGCCGGCC TCCBCCBGGG BCBTGGTCCT TCTTGTCCGC TGCCTCTCTG GGGTTTTCGG TCTGGGTGGG CTTCCTCCT GGGGCTGCTG CTGGGCTCTT CTTTGTTT CTGGCCTGGT GCTCTCTCGT GCCCTTTCCC TTGGGTGTCT TGTTTGTG GCCTCCBCCB GGGBCBTG-3' (FRAG. NO:1789) (SEQ. ID NO: 1802) 5'-CGGGBGTGGG GG-3 ' (FRAG.NO:1790) (SEQ. ID NO: 1803) WO 00/62736 PCT/USOO/08020 211 5'-GCCBGCBCCCC-3' (FRAG.NO:1791) (SEQ. ID NO: 1804) 5'-C CBC CBG-3' (FRAG.NO:1792) (SEQ. ID NO: 1805) 5'-GGC CTC CBC CBG GGB CBT G-3' (FRAG. NO:1201) (SEQ. ID NO:1210) 5'-GTC CTT CTT GTC CGC TGC C -3' (FRAG. NO:1202) (SEQ. ID NO:1211) 5 5'-TCT CTG GGG TTT TCG GTC TGG GTG G-3 (FRAG. NO:1203) (SEQ. ID NO:1212) 5'-GCT TC CTC CTG GGG CTG CTG CTG-3' (FRAG. NO:1204) (SEQ. ID NO:1213) 5'-GGC TCT TCT TTT TGT TTC TGG CCT GGT G-3' (FRAG. NO:1205) (SEQ. ID NO:1214) 5'-CTC TCT CGT GCC CTT TCC-3' (FRAG. NO:1206) (SEQ. ID NO:1215) 5'-CTT GGG TGT CTT GTT TTT GT-3' (FRAG. NO:1207) (SEQ. ID NO:1216 10 5'-GGC CTC CBC CBG GGB CBT G-3' (FRAG. NO:1208) (SEQ. ID NO:1217) 5'-CGGGBGTGGG GGTCCTGGBC GGCBCTGBBG GCBTCCBGGG CTCCCTTCCB GTCCT'TCTTG TCCGCTGCCB GCBCCCCTTC BTTCCBGBGG CTGBTGGCCT CCBCCBGGGB CBTGBTTBGG TBGBBBCTBG GBGGCC-3' (FRAG. NO:1793) (SEQ. ID NO: 1806) Human Cathepsin G Nucleic Acid and Antisense Oligonucleotide Fragments 15 5'-CCCTCCBCBT CTGCTCTGBC CTGCTGGBCT CTGGBTCTGB BGBTBCGCCB TGTBGGGGCG GGBGTGGGGC CTGCTCTCCC GGCCTCCGBT GBTCTCCCCT GCCTCBGCCC CBGTGGGTBG GBGBBBGGCC BGCBGBBGCB GGBGTGGCTG CBTCTTTCCT GGTGGGGCCT GCTCTCCCGG CCTCCGTGTG TTGCTGGGTG TTTTCCCGTC TCTGGTCTGC CTTCGGGGGT CGT-3' (FRAG. NO:1794) (SEQ. ID NO: 1807) 5'-GBBGBTBCGCC-3' (FRAG. NO:1795) (SEQ. ID NO: 1808) 20 5'-CBGCCCCBG-3' (FRAG. NO:1796) (SEQ. ID NO: 1809) 5'-TCC CGT CTC TGG-3' (FRAG. NO:1797) (SEQ. ID NO: 1810) 5'-GTG GGG CCT GCT CTC CCG GCC TCC G-3' (FRAG. NO:1209) (SEQ. ID NO:1218) 5'-TGT GTT GCT GG GTG TTT TCC CGT CTC TGG-3' (FRAG. NO:1210) (SEQ. ID NO:1219) 5'-TCT GCC TTC GGG GGT CGT-3' (FRAG. NO:1211) (SEQ. ID NO:1220) 25 5'-CCCTCCBCBT CTGCTCTGBC CTGCTGGBCT CTGGBTCTGB BGBTBCGCCB TGTBGGGGCG GGBGTGGGGC CTGCTCTCCC GGCCTCCGBT GBTCTCCCCT GCCTCBGCCC CBGTGGGTBG GBGBBBGGCC BGCBGBBGCB GGBGTGGCTG-3' (FRAG. NO:1798) (SEQ. ID NO: 1811) Human Defensin 1 Nucleic Acid and Antisense Oligonucleotide Fragments 5'-CCGGGGCTGC BGCBBCCTCB TCBGCTCTTG CCTGGBGTGG CTCBGCCTGG GCCTGCBGGG CCBCCBGGBG 30 BBTGGCBGCB BGGBTGGCGB GGGTCCTCBT GGCTGGGGTC BCBGBTCCTC TBGCTBGGCB GGGTGBCCBG BGBGGGC GGG TCC TCB TGG CTG GGG GCC TGG GCC TGC BGG GCC GCT CTT GCC TGG BGT GGC TC GCC CBG BGT CTT CCC TGG T GCTCAGCCTC CAAAGGAGCC AGCCTCTCCC CAGTTCCTGA AATCCTGAGT GTTIGCCTGCC AGTCGCCATG AGAACTTCCT ACCTTCTGCT GTTTACTCTC TGCTTACTTT TGTCTGAGAT GGCCTCAGGT GGTAACTTTC TCACAGGCCT TGGCCACAGA TCTGATCATT ACAATTGCGT CAGCAGTGGA 35 GGGCAATGTC TCTATTCTGC CTGCCCGATC TTTACCAAAA TTCAAGGCAC CTGTTACAGA GGGAAGGCCA AGTGCTGCAA GTGAGCTGGG AGTGACCAGA AGAAATGACG CAGAAGTGAA ATGAACTTTT TATAAGCATT CTTTTAATAA AGGAAAATTG CTTTTGAAGT AT CTGCAGTGGT AAAAAGATTC TATATCTGCT GTTTGATGAA TGCAGCACCC ACTAGCCACA TAGTGCTCGT GAGCACTTGC AATGCGGCTA GGGTGATTTC AAITAACCTA AAAGAGAACA GCCACAGGGA GCATGTGGCT GCCATATTGG ATGGTGCTGC TTTGAGAACA AAATGAGAGA 40 AATGAAGCCT CTATTTACCT TGGTTGGCGG AACACATTGA AGGGACTCTG TATTGATACC AGGCTTCAAA CT'TTGGGAAG TGTACTGGCC AACTTAAACA CATCCACAGG AGAATGAAGA GGTTFTGGGAA GGGACCAGAA ACCAGGCATT GAGGACAATG AGAAGAGTTT TTCAAAAGTG GAATTACTGC AAAAAGTGGA AAAATAGCCT TTGGATGGAA GTTACTGATG AGACAATTTC CATCGGTGTG AAAGCCATCT TTCCAACAGA GATCTGCAAC ATGAGAATGT ACTGTCTCCT AGGGTAGCGA TGGCCTCTTG TATTAGTCCG CTCAGGCTAC CAGATTTATC 45 GTTTAAACTG CCCATAAACA GACCAGGCAG TTTAAACAAC AGAAATTTAT TTCCTCGCAG TCCTGGAGGC AGGAAGTCTG CGATCAAGGT GGAAGCAGGG TTGGCTTCTT CTCAGGTGTC TGTCCTTGGC TGGTAGATGA CCGCCGCCTC CCTGGGTCCT CACATGGTCT TTCCTCTGTG TGTGTCTGTC CCAATCTCTT CTTATAAGGA TGCAAGTCTT ATGGATCAGA GCACACCCCA ATGACCGTGT TTAACTTGAA TCACCTCTTT AAAGTTTCTC TCTCCAAATA CAATCACCTC CTGAGGCACT GTTAGGGCTT CGACACAGGA ATTCTTCC TAGGGGATTC 50 AGTTCAGTCC AAAACGCCTA CCAGTGGAGA CTTGCAACAT GGCGGCCTGC TGGTCCCTCG CCAGGAATAT CACAGGCGAC TGTTCCCTGT TGCATGGAAT AGAAGGCTAT TCCAGAGTAC TGTCTCTAITT TATCAGATCT GGGATACTGG GAGAAGGGCA AAATAAAGTC CAAGTAGAAA AAAAAACTAT GAAAGTTTTA GAGAGTAACC ATAATT'TCAG CCCGATGTGA AACGATCCTA GATTTCAGCT GAAATAGTGA TGTGGGAAGT GAGGGGGCCG GGATTCAAGG CAGAGGGAAC AGCGTAACTG AAGGCATGGA AGGAGGGAAG TGTAGGCTGT GTTTGAAGAG 55 TGGCAGCTGC TTCCACATTT CTAAAACACA GGATGTGATT TTGGGGTGTG TTGAGACAAG GCAGAAAACT TGTTTGGAAA AATAACTTGA ATTCCCTGCA CATTTAAAAT CTCTCAGCAG AAGAAAACCC CACTCAGAAC CCCACTGTTC ATTCCTTGGC TTGTATTTGG SCACAGCTGG CATAGCCCCA GACTGAGTAA GCTCTTCAGA CACCTCATTT CATGAGTAGC CCCAAAGATC AATCATGGGC CAATT'TCTTG GAAGAGAAGA CTCTCCGGTG TTTTGCAGTT ATTTGTFCTG CTTTCGCGAG ATGTTCTCAA ATCGTTGCAG CTACAAGCCA TGAGTCTGAA 60 GTGTTTGTGT TCCCTCCTTA CAGGTGGTAA CTTTCTCACA GGCCTTGGCC ACAGATCTGA TCATTACAAT TGCGTCAGCA GTGGAGGGCA ATGTCTCTAT TCTGCCTGCC CGATCTTTAC CAAAATTCAA GGCACCTGTT ACAGAGGGAA GGCCAAGTGC TGCAAGTGAG CTGAGAGTGA CCAGAAGAAA TGACGCAGAA GTGAAATGAA CTTTATAA GCATTCTTTT AATAAAGGAA AATTGCTTTT GAAGTATACC TCCTTTGGGC CAAAATGAAT CTTGTGTCTC AATTGGAAGA GGTAAAGAAG TAGGGGGTTA GGGTGCATGG GTTGGAACGT GAGACAGGTC 65 GAACCACAAA GCCTGCCTGG AAAAGGGGAG TGACGTCCTA GGCTTCAGTG ATGTCACCTC CACTTTGTTT WO 00/62736 PCT/USOO/08020 212 GATCCACAAA CCAACAGGTG ACTGATTTG GTCAGCTCAG CCTCCAAAGG AGCCAGCCTC TCCCCAGTTC CTGAAATCCT GAGTGTTGCC TGCCAGTCGC CATGAGAACT TCCTACCTTC TGCTGTTTAC TCTCTGCTTA CTTTTGTCTG AGATGGCCTC AGGTGGTAAC TTTCTCACAG GCCTTGGCCA CAGATCTGAT CATTACAATT GCGTCAGCAG TGGAGGGCAA TGTCTCTATT CTGCCTGCCC GATCTTACC AAAATTCAAG GCACCTGTTA 5 CAGAGGGAAG GCCAAGTGCT GCAAGTGAGC TGGGAGTGAC CAGAAGAAAT GACGCAGAAG TGAAATGAAC TT -3' (FRAG.NO:1799) (SEQ. ID NO: 3010) 5'-GTCAGCTCAG CCTCCAAAGG AGCCAGCCTC TCCCCAGTTC CTGAAATCCT GAGTGTTGCC TGCCAGTCGC CATGAGAACT TCCTACCTTC TGCTGTTAC TCTCTGCTTA CTTTTGTCTG AGATGGCCTC AGGTGGTAAC TTTCTCACAG GCCTTGGCCA CAGATCTGAT CATTACAATT GCGTCAGCAG TGGAGGGCAA TGTCTCTATT 10 CTGCCTGCCC GATCTTTACC AAAATTCAAG GCACCTGTTA CAGAGGGAAG GCCAAGTGCT GCAAGTGAGC TGGGAGTGAC CAGAAGAAAT GACGCAGAAG TGAAATGAAC TT-3' (FRAG.NO:__) (SEQ. ID NO: 2475) 5'-CTGCAGTGGT AAAAAGATTC TATATCTGCT GTTTGATGAA TGCAGCACCC ACTAGCCACA TAGTGCTCGT GAGCACTTGC AATGCGGCTA GGGTGATTTC AATAACCTA AAAGAGAACA GCCACAGGGA GCATGTGGCT GCCATATTGG ATGGTGCTGC TTTGAGAACA AAATGAGAGA AATGAAGCCT CTATTTACCT TGGTTGGCGG 15 AACACATTGA AGGGACTCTG TATTGATACC AGGCTTCAAA CTTGGGAAG TGTACTGGCC AACTTAAACA CATCCACAGG AGAATGAAGA GGTTTGGGAA GGGACCAGAA ACCAGGCATT GAGGACAATG AGAAGAGT TTCAAAAGTG GAATTACTGC AAAAAGTGGA AAAATAGCCT TTGGATGGAA GTTACTGATG AGACAATTTC CATCGGTGTG AAAGCCATCT TTCCAACAGA GATCTGCAAC ATGAGAATGT ACTGTCTCCT AGGGTAGCGA TGGCCTCTTG TATTAGTCCG CTCAGGCTAC CAGATTATC GTTTAAACTG CCCATAAACA GACCAGGCAG 20 TAAACAAC AGAAATTTAT TTCCTCGCAG TCCTGGAGGC AGGAAGTCTG CGATCAAGGT GGAAGCAGGG TTGGCTTCTT CTCAGGTGTC TGTCCTTGGC TGGTAGATGA CCGCCGCCTC CCTGGGTCCT CACATGGTCT TTCCTCTGTG TGTGTCTGTC CCAATCTCTT CTTATAAGGA TGCAAGTCTT ATGGATCAGA GCACACCCCA ATGACCGTGT TTAACTTGAA TCACCTCTT AAAGTTTCTC TCTCCAAATA CAATCACCTC CTGAGGCACT GTTAGGGCTT CGACACAGGA ATTCTTTTCC TAGGGGATTC AGTTCAGTCC AAAACGCCTA CCAGTGGAGA 25 CTTGCAACAT GGCGGCCTGC TGGTCCCTCG CCAGGAATAT CACAGGCGAC TGTTCCCTGT TGCATGGAAT AGAAGGCTAT TCCAGAGTAC TGTCTCTATT TATCAGATCT GGGATACTGG GAGAAGGGCA AAATAAAGTC CAAGTAGAAA AAAAAACTAT GAAAGTTTA GAGAGTAACC ATAATTTCAG CCCGATGTGA AACGATCCTA GATTCAGCT GAAATAGTGA TGTGGGAAGT GAGGGGGCCG GGATTCAAGG CAGAGGGAAC AGCGTAACTG AAGGCATGGA AGGAGGGAAG TGTAGGCTGT GTTTGAAGAG TGGCAGCTGC T7CCACATTT CTAAAACACA 30 GGATGTGATT TTGGGGTGTG TTGAGACAAG GCAGAAAACT TGTTTGGAAA AATAACTTGA ATTCCCTGCA CATTTAAAAT CTCTCAGCAG AAGAAAACCC CACTCAGAAC CCCACTGTTC ATTCCTTGGC TTGTATTTGG SCACAGCTGG CATAGCCCCA GACTGAGTAA GCTCTTCAGA CACCTCATTT CATGAGTAGC CCCAAAGATC AATCATGGGC CAATTTCTTG GAAGAGAAGA CTCTCCGGTG TTTTGCAGTT ATTTGTTCTG CTTTCGCGAG ATGTTCTCAA ATCGTTGCAG CTACAAGCCA TGAGTCTGAA GTGTTTGTGT TCCCTCCTTA CAGGTGGTAA 35 CTTTCTCACA GGCCTTGGCC ACAGATCTGA TCATTACAAT TGCGTCAGCA GTGGAGGGCA ATGTCTCTAT TCTGCCTGCC CGATCTTTAC CAAAATTCAA GGCACCTGTT ACAGAGGGAA GGCCAAGTGC TGCAAGTGAG CTGAGAGTGA CCAGAAGAAA TGACGCAGAA GTGAAATGAA CTTTATAA GCATTC'TT AATAAAGGAA AATTGCTTT GAAGTATACC TCCTTTGGGC CAAAATGAAT CTTGTGTCTC AATTGGAAGA GGTAAAGAAG TAGGGGGTTA GGGTGCATGG GTTGGAACGT GAGACAGGTC GAACCACAAA GCCTGCCTGG AAAAGGGGAG 40 TGACGTCCTA GGCTTCAGTG ATGTCACCTC CACTTGTTT GATCCACAAA CCAACAGGTG ACTGATTTTG-3' (FRAG.NO:_) (SEQ. ID NO: 2474) 5'-GCTCAGCCTC CAAAGGAGCC AGCCTCTCCC CAGTTCCTGA AATCCTGAGT GTTGCCTGCC AGTCGCCATG AGAACTTCCT ACCTTCTGCT GTTTACTCTC TGCTTACTTT TGTCTGAGAT GGCCTCAGGT GGTAACTTTC TCACAGGCCT TGGCCACAGA TCTGATCATT ACAATTGCGT CAGCAGTGGA GGGCAATGTC TCTATTCTGC 45 CTGCCCGATC TTTACCAAAA TTCAAGGCAC CTGTTACAGA GGGAAGGCCA AGTGCTGCAA GTGAGCTGGG AGTGACCAGA AGAAATGACG CAGAAGTGAA ATGAACTTT TATAAGCATT CTTTTAATAA AGGAAAATTG CTTTTGAAGT AT-3' (FRAG.NO:__) (SEQ. ID NO: 2472) 5'-CCGGGGC-3' (FRAG.NO:1800) (SEQ. ID NO: 1813) 5'-GG GCCTGCBGGG CC-3' (FRAG.NO:1801) (SEQ. ID NO: 1814) 50 5'-GGCBGCB BGG-3' (FRAG.NO:1802) (SEQ. ID NO: 1815) 5'-GGG TCC TCB TGG CTG GGG-3' (FRAG. NO:1212) (SEQ. ID NO:1221) 5'-GCC TGG GCC TGC BGG GCC-3' (FRAG. NO:1213) (SEQ. ID NO:1222) 5'-GCT CTT GCC TGG BGT GGC TC-3' (FRAG. NO:1214) (SEQ. ID NO:1223) 5'-GCC CBG BGT CTT CCC TGG T-3' (FRAG. NO:1215) (SEQ. ID NO:1224) 55 5'-CCGGGGCTGC BGCBBCCTCB TCBGCTCTTG CCTGGBGTGG CTCBGCCTGG GCCTGCBGGG CCBCCBGGBG BBTGGCBGCB BGGBTGGCGB GGGTCCTCBT GGCTGGGGTC BCBGBTCCTC TBGCTBGGCB GGGTGBCCBG BGBGGGC-3' (FRAG.NO:1803) (SEQ. ID NO: 1816) Human Defensin 2 Nucelic Acid and Antisense Oligonucleotide Fragments 5'-ATCCTTTAAG TCAATGGACT TTGCATCAGT CACACCATCT TTTGTTACTT TGGACTTCCC CAGCTATGT7 60 CAATAATTAC TGTTCTTCCC TTGGGCCCCA TTGTAATGGC TACAGCCTCG ACAAAAAGTC TACACTTTGA AGCATTAAGG CTCGGACATC AGCACCAAAT TTTACATCTTr TACCATCACT TCAAGTGAGG TGAGGAGCCA GTAGCCTGGA CACTGGTCTC ATCTGGTGAA AGACTGTGGG TAATGGAAGC ATTTCTGTGG GGTGCTGGCA GGACATGTGC ATGGCGAGGC AGGTCATCAG CAGCAAGTGA GAGCTGCCTC TTACTTTCTA AAGGTGACAT AGCAAATATA CAAAAAAAAA TAAATAAATT ATTAATTTAG GTAGAGCACA TAAAGGCTTT ATTTCATATT 65 CCATTTCTCT GTATGCTTTC TTCACCAGGA AGAAATAGTT TTAGTGTCAG GAATGAATGA GTCTGCCCCT WO 00/62736 PCT/USOO/08020 213 CAATTCCAGC CTGCTCAACA CACAAGGAAA CAAAGCCCTG ACAATCAGAG TGACTCCCTG GTGACTAAGC TCCCAGTCCT GGATGCATAT TTGTTTAGCA GTTCTGACAG CATTTGACCC AGCCCTCTCT CTGCATATCC CATCAGAACC TTCTTTTTTT TTTTTTTCTT TGAGACTGAG TCTTGCTCTG TCGGAAGCGA CTCCTGTGCC TCAGCCTCCC AAATACCTGG AATTATAGGC GTAAGCCATC ATGCCTGGCT AATTGTA TITTCATGG 5 AGATGGGGTT TTGCCATGTT GGTCAAATTG GTCTCACACT CCTGACCTCA TGTGATCCAC CTGCCTCAGC CTCCCAAACT GCTGGGATGA CAGGTGTAAG CCACCATGCT AGGCTCAGAA ATTTCCTTTT ATAAAAATGT CATTAAGGAT CTTGGCTGCA CAATATCGTT ACCAGCTTCC TTTAAATCCA CTT7CTGGCCT GCCAGGAATC AGGTTCTTCA GAACCTGACA TTTTAAATGA AGAGGTCAGG CAGTTCATGA GGAAAGCCTC ATTGTCCCCA TGTCTCTGTC ACTGCTGCAC CCCTGAGACA TCACAGACAT GGACACTGGG GCCTGCTTGT TTCTCAAACT 10 GCCC17AGAT CGAAAGAGGG AGGAACCAGG ATGAATGCCA CTCATTCC CAAGAAAGGC CCTCTCCTGA GTGCCCGGGA TGGGGCTCTG TCCATTGCCT GGGGCCGCCA ATTGCTACTC TGGGTTACGG AGGAAGGACA GGGTCCTGAG AGACACCAGA GACCTCACAC AGCCCTGAAA ACATGGGGCT CCTTCATAAG TGTTCCCAT CACCAACAGG GAGACCACGT GGAGGCCTTG CAGCCCCACT CGGTGCTTCT CCACCAAATC CCAAGGGCAG TGACGCTGAC GTCTGTGGAA AGCAGAGAAA GCCCTGGCTC CCAAAGCCCT GAAGTCCCTG TGGAGCTGAC 15 ATTCCCTGAG TGACGGTGTG AATGGAAGGA ACTCAAGTGC GGGTGGTAGG CCACCTCCTG GCCCAGGCCT GGGTGAACTC TGAGGGGACA CATGTAGTCA CAATCCCATC CTCCCATTCT CCTTCTCAGA GGAAGGAAGT GGGCATCCAT CTGCCTCATC TCTCTCCCGT GGGGAAGATG GGGAGTTTCA GGGGAACTTT CACATAAATT TCACCAGCTC AGATCTCCTG TGAGGATGGG GCCCACCATG CTCCCGGTGC TGCCAGAGGC CCTGAGCCCC TCCCAGGGTC CCTGGGTTG AGCCAGCCCT GTATCATCCC CAGGAGCTGA ATGTCAGAGC AATGGATAGA 20 ATTAGATGGA AAGAGCTCTC AATTrGACCT GAGACTGTCC CCAGATACTC AGGAAAAACA GGACGTCGCA CAGAGTGGGC AGCAGGTGAG TGGCAGGTTA TAGGTCCTGA GTTFGAGTTT GTTCTCACGT GAGACAGACC CAGCCCCTCA CTCCATTCAC ACACTGGGTT TTAAATGGTG CAAGATAGGA GCAATTCT GGTCCCAAGA GCAGGAGGAA GGGATTTTCT GGGGTT7CCT GAGTCCAGAT TTGCATAAGA TCTCCTGAGT GTGCATTGTT CTTTGAGGAC CATTCTCTGA CTCACCAGGT AAGTGGCTGA ATTCTAACCT CTGTAATGAG CATTGCACCC 25 AATACCAGTT CTGAACTCTA CCTGGTGACC AGGGACCAGG ACCTTTATAA GGTGGAAGGC TTGATGTCCT CCCCAGACTC AGCTCCTGGT GAAGCTCCCA GCCATCAGCC ATGAGGGTCT TGTATCTCCT CTTCTCGTTC CTCTTCATAT TCCTGATGCC TCTTCCAGGT GAGATGGGCC AGGGAAATAG GAGGGTTGGC CAAATGGAAG AATGGCGTAG AAGTTCTCTG TCTCCTCTCA TTCCCCTCCA CCTATCTCTC CCTCATCCCT CTCTCTCCTT CCTCTCTCTG TGTGTCCCCT CCATCCTTT CTCCTGCTTC TCTCTCTTCT TCCCTCTCTC TCTTTTTTCT 30 GTCTTTCTTT TTCCTCTCTC CCTAGAGCAT GTCTTrCTTT CTTCTCTTT CCTTTCTTCT ACCCACACTT TTAGACTGAA TGCCCTATTT AATTGAACAA AGCATTGCTT CCTTCAATAG AAAAGGAGTT TGAGAACCCA ATGGACACCT CACTCGTTCT TCTAAGCCAA TATGAAGGAG CCCAGTAGCT TGTAAATATC ATCTCTTCAC TGCTTTCCAT GCTACAACTG CTGAGACTAT GGTTGAAACC TGTTAGGTGA CTTTAAAT AAAAGGCAGA AATTTTGATT TTATCTAAAG AAAGTAGTAT AGAATGTCAT TTTCTAAATT TTTATATTA AAGGGTAGAT 35 ACTGCAACCT AGAGAATTCC AGATAATCTT AAGGCCCAGC CTATACTGTG AGAACTACTG CAGCAAGACA CTCTGCCTCC AGGACTTTTC TGATCAGAGG CCCTGAGAAC AGTCCCTGCC ACTAGGCCAC TGCAGGTTCA CAGGACAGGG TACAGCCCAT TGAAACCTAC TTTAAACCT GGATGCCTAA CCTTCATTT CTCCTTGATA TTATGAAAAT AAAATAAAAA CCATGAAAGG ATAAAAGAGG GAGAGTGGAA GGGAAGGATG GAGAAAGGGA AAAAGAAAAT TTGAGAGTAA ATCCTAAAAC AATTAATCTA ATAGATATCA TCTTGTGAAA TCCTCATT 40 ACCAATCTTA TTTATGAGTC CTGGGTTG TGAGAACAAT GGGGTTCTGA GAGGCACCAG AGACCTCATG TTTTCCAAAA CCTAGAACAG TATAATGAAG GAAGGCGGGG AGGCAGGGAG GCAGGGAGGC AGGGAGGCAG GGAGGCGGGC AGGTGGGGAG GGAGGGACGG AAGGAGGGAG GGAGGGAGGG AGGGAGGGAG GGAGGGATAA AAAAAGAAGA ATGAGGTTGA AACCAGGACT TAGATATTAG AAACAAGCCA TTACAAAATT TATTTCTATG GTTAATTGTG GTTTTCAACT GTAAGTTACT TGGTGTTAAT TTCCTATrAA ACAATTCAG TAAGTTGCAT 45 CT-TATCC CATCTCAGGT CAAATACTTA ACAGACTAAA TGATTGAAA AAGCAAAAGT TTACTGGCTT GTGTGTGTTA AAATGGAGGT ATGGTGGCTT TGATATTATC TTCTTGTGGT GGAGCTGAAT TCACAAGAGA TCGTTGCTGA GCTCCTACCA GACCCCACCT GGAGGCCCC.A GTCACTCAGG AGAGATCAGG GTCTTTCACA ATCAGGTTCT ACAAAAATAA ACATCCCCCC AACCACAGCA GTGCCAGTTT CCATGTCAGA AACTTAGATC CAAATGACTG ACTCGCGTCT CATTATCATG ATGGAAAAGC CCAGGCTTGA GAAAGAAGCC CGCTGCGGAT 50 TTACTCAAGG CGATACTGAC ACAGGGTTTG TGTTCCA ACATGAGTTT TGAGTTCTTA CACGCTGTTT GCTCTTTG TGTGTTTT CCCTGTTAGG TGTT GGT GGTATAGGCG ATCCTGTTAC CTGCCTTAAG AGTGGAGCCA TATGTCATCC AGTCTTGC CCTAGAAGGT ATAAACAAAT TGGCACCTGT GGTCTCCCTG GAACAAAATG CTGCAAAAAG CCATGAGGAG GCCAAGAAGC TGCTGTGGCT GATGCGGATT CAGAAAGGGC TCCCTCATCA GAGACGTGCG ACATGTAAAC CAAATTAAAC TATGGTGTCC AAAGATACGC AATCTTrATC 55 CTAGTAATTG TGGTCATTGG GTGATGTTGG TTTGGGCAGG CCATCTCTAA TATCCTrGAA ACACCTTT CTGCTCTCCA GGAAGGGGTC AGGGCTGCCA CAGCGGGGCT TGGAGTGCTT TCCAGGGTCA CAGGCATCTG TATTCTTTGG ATTCCTTGAC CTTCCCCATT TATTCCCGGC ATTTTCCTAA AACGTGTGCT TT1GCTCCTCC TGCATCCTCC CCTTGCATGC CCTCACCTAC CCCACATCTT CCCTAAAAAA AGCAAGCCCA ACTCAAAGAC CAGTTCCCTC ATGGAATCAT AGTGGATCTG CCAAGGGAGG GGATGCCCAG TCCTCTGTTC TTCACAAGAC 60 TCCCTTCTTC TGGCTAAGGT TTCTTATGCA ATTAT GAATTCACAT T7CTCACCTTI TTGATGTATT AAGAAAGTAT GGAGAAATAT ATCCTCTATC AAATTTTCAT GCCTTCAATA ATTTCTAATT CATCAGTCAG TGTTTCCA TCCTTTACTG TGATGATGCC CTTCTTCCA AACTTTCA TTGCATCAGA GATGATGTTA CCAATTTCTT TGTCTCCATT TGCAGAAATT GTAGCAACCT GTGCAATTTC TTCAGGTTTG GTCACAGGTT TAGACTGCTT TTTAAGTTCA GCAATTACAG CATCAACAGC TAACATCACA CCTCTCTTGA TTTCCACTGG 65 ATTAGCACCT TTGCTAACCT TCTGGAAGGC TTATTGGAA ATAGAGCATA CCAGTACAGC AGCAGTGATA GTGCCATCCC CCAGTCTCTC CATTTGTGTT ATTGGCAACA TCTTGGACAA GTTTAGCTCC AATGCTTTTA WO 00/62736 PCT/USOO/08020 214 TA'TATCCT TTAAGTCAAT TGACTTrGCA TCAGTCACAC CATCTI=GT TAC'IMGGGA CTTCCCCAGC TATGTTCAAT AATI1ACTGTT C~rCCCTTTG GCCCCATTGT AATGGCTACA GCATCGACAA AAAGTCTACA CITTGAAGCA T7AAGGCTCA GACATCAGCA CCAAA'ITrA CATC'ITTACC ATCACTrCAA GTGAGGTGAG GAGCCAGTAG CCTGGACACT GGTCTCATCT GGTGAAAGAC TGTGGGTAAT GGAAGCAT CTGTGGGGTG 5 GTGGCAGGAC ATGTGCATGG TGAGGCAGGT CATCAGCAGC AAGTGAGAGC TGCCTC'ITAC TTTCTAAAGG TGACATAGCA AGTATACAAA AAAAAATAAA ATATTAAT AGGCAGAGCA CATAAAGGCT. TTA1TTCATA TTCCATTTCT CTGTATGCTT TCTTCACCAG GAAGAAATAG TITAGTGTC AGGAATGAAT GAGTCTGCCC CTCAAT'FCCA GCCTGCTCAG CACACAAGGA AACAAAGCCC TGACAATCAG AGTGACTCCC TGGTGACTAA GCTCCAGTCC TGGATGCATA '1GTTTAGC AGTrCTGACA GCATCTGACC CAGCCCTCTC =ITGCATACC 10 CCACCAGAAC CTTCTTI TITTTIC TrrGAGACTG AGTCT-rGCTC TGTCGGAAGC GATI'CCCGTG CCTCAGCCTC CCAAATACCT GGAATTATAG GCGTAAGCCA TCATGCCTGG CTAATTrG TATFTTCAT GGAGATGGGG TITGCCATG TTGGTCAAAT TGGTCTCACA CTCCTGACCT CATGTGATCC ACCTGCCTCA GCCTCCCAAA GTGCTGGGAT GACAGGTGTA AGCCACCATG CTAGGCTCAG AAKITTTCCTT TrATAAAAAT GTCATTAAGG ATCYrGGCTG CACAATATCG TTACCAGCTr CCTTTAAATC CACCTCTGGC CTGCCAGGAA 15 TCAGGGTrCT TCAGAACCTG ACAT=~AAA TGAAGAGGTC AGGCAGGTCA TGAGGAAAGC CTCATTGTCC CCATGTCTCT GTCACTGCTG CACCCCTGAG ACATCACAGA CATGGACACT GGGGCCTGCT TGYI1?CTCAA ACTGCCCYTA GATCGAAAGA GGGAGGAACC AGGATGAATG CCACTCATTT TCCCAAGAAA GGCCCTCTCC TGAGTGCCCG GGATGGGGCT CTGTCCATTG CCTGGGGCCG CCAATTGCTA CTCTGGGTFA CGGAAGAAGG ACAGGGTCCT GAGAGACACC AGAGACCTCA CACAGCCCTG AAAACATGGG GCTCCTTCAT AAGTGTITTCC 20 CATCACCAAC AGGGAGACCA CGTGGAGGCC TrGCAGCCCT ACTCGGTGCT TCTCCACCAA ATCCCAAGGG CAGTGACGCT GACGTCTGTG GAAAGCAGAG AAAGCCCTGG CTCCCAAAGC CCTGAAGTCC TGTGGAGCTG ACATTCCCTG AGTGACGGTG TGAATGGAAG GAACTCAAGT GCGGGTGGTA GGCCACCTCC TGGCCCAGGC CTGGGTGAAC TCTGAGGGGA CACATGTAGT CACAATCCCA TCCTCCCATT CTCCTTCTCA GAGGAAGGAA GTGGGCATCC ATCTGCCTCA TCTCTCTCCC GTGGGGAAGA TGGGGAGTT CAGGGGAACT TTCACATAAA 25 'ITTCACCAGC TCAGATCTCC TGTGAGGATG GGGCCCACCA TGCTCCCGGT GCTGCCAGAG GCCCTGAGCC CCTCCAGGGT CCCTGGGT GAGCCAGCCC TGTATCATCC CCAGGAGCTG AATGTCCGAA CAATGGATAG AATTAGATGG AAAGAGCTCT CAATTTGGCC TGAGACTGTC CCCAGATACT CAGGAAAAAC AGGACGTCGC ACAGAGTGGG CAGCAGGTGA GTGGCAGGTT ATAGGTCCTG AG'TrGAGTr TGTTCTCACG TGAGACAGAC CCAGCCCCTC ACTCCATFCA CACACTGGGT TTTAAATGGT GCAAGATAGG AGGAATITC TGGTCCCAAG 30 AGCAGGAGGA AGGGA'IFC TGGGGTI'TCC TGAGTCCAGA ITTGCATAAG ATCTCCTGAG TGTGCATTGT TCITTGAGGA CCATTCTCTG ACTCACCAGG TAAGTGGCTG AATTCTAACC TCTGTAATGA GCATTGCACC CAATACCAGT TCTGAACTCT ACCTGGTGAC CAGGGACCAG GACCn7TATA AGGTGGAAGG CTTGATGTCC TCCCCAGACT CAGCTCCTGG TGAAGCTCCC AGCCATCAGC CATGAGGGTC TTGTATCTCC TC FrCTCG'rr CCTCTrFCATA TrCCTGATGC CTCT-rCCAGG TGAGATGGGC CAGGGAAATA GGAGGGTTGG CCAAATGGAA 35 GAATGGCGTA GAAGTT1CTCT GTCTCCTCTC ATTCCCCTCC ACCTATCTCT CCCTCATCCC TCTCTCTCCT TCCTCTCTCT GTGTGTCCCC TCCATCCIT TCTCCTGC'r CTCTCTCTTC TrCCCTCTCT CTCTTTTTI CTGTCTICT TITTCCTCTC TCCCTAGAGC ATGTCTTTCT TTITCTCT TTr TT' CTACCCACAC TTTTAGACTG AGTAGACTGA ATGCCCTATT TAATTGAACC AAGCATTGCT TCCTTCAATA GAAAAGGAGT TTGAGAACCC AATGGACAAC TCACTCGTTC TTCTAAGCCA ATATGAAGGA GCCCAGTAGT TrGTAAATAT 40 CATCTCTCA CTGC'TrCCA TGCTACAACT GCTGAGACTA TGGTrGAAAC CTGTTAGGTG AC TTTAAA TAAAAGGCAG AAATPGAT 'TTrATCTAAA GAAAGTAGTA TAGAATGTCA TITCTAAAT TITr1ATAM~ AAAGAGTAGA TACTGCAACC TAGAGAATTC CAGATAATCT TAAGGCCCAG CCTATACTGT GAGAACTACT GCAGCAGACA CTCTGCCCCC AGGACTITTC TGATCAGAGG CCCTGAGAAC AGTCCCTGCC ACTAGGCCAC TGCAGGTI'CA CAGGACAGGG ACAGCCCATT GAAACCAACT TAAACCTG GATGCCTAAC CTTCATTTTC 45 TCCTI7GATAT TATGAAAATA AAATAAAAAC CATGAAAGGA TAAAAGAGGG AGAGTGGAAG GGAAGGATGG AGAAAGGGAA AAAGAAAAYI' TGAGAGTAAA TCCTAAAACA ATTAATCTAA TAGATATCAT CTTGTGAAAT CCTCATITA CCAATCTTAT TTATGAGTCC TGGGTTIGT GAGAACAATG GGGTITCTGAG AGGCACCAGA GACCTCATAT T1TCCAAAAC CTAGAACAGT ATAATGAAGG AAGGAGGGAA GGAGGGAGGG AGGGAGGGAA GGAGGGAAGG AGGGAGGGAG GGAGGGAAAC AAAAAGAAGA ATGAGGTrGA AACCAGGACT TAGATAYTAG 50 AAACAAGCCA TTACAAAATI' TATTFCTATG GTTAAT-FGTG GrI=CAACT GTAAGTTACT TGGTGTTAAT TTCCTATTAA ACAATCAG TAAGTTGCAT C'TTrATC CCATCTCAGA TCAAATACTT AACAGACTAA ATGATTTGAA AAAGCAAAAG TrTACTGGCT TGTGTGTGTT AAAATGGAGG TATGGTGGCT TTGATATTAT CTTCTrGTGG TGGAGCTGAA TTCACAAGAG ATCGTTGCTG AGCTCCTGCC AGACCCCACC TGGAGGCCCC AGTCACTCAG GAGAGATCAG GGTCTTTCAC AATCAGGT7C TACAAAAATA AACATCCCCC AAACCACAGC 55 AGTGCCAGTI7 TCCATGTCAG AAACTTAGAT CCAAATGACT GACTCGCGTC TCATTATCAT GATGGAAAAG CCCAGGCTT1G AGAAAGAAGC CCGCTGCGGA 'ITTACTCAAG GCGATACTGA CACAGGGTrF GTGTIT=CC AACATGAGTT 'FrGAGTTC'rr ACACGCTGTT TGCTCTI= GTGTGTrT TCCCTGTTAG GTGTTTIGG TGGTATAGGC GATCCTGT7A CCTGCCTTAA GAGTGGAGCC ATATGTCATC CAGTCTITG CCCTAGAAGG TATAAACAAA TTGGCACCTG TGGTCTCCCT GGAACAAAAT GCTGCAAAAA GCCATGAGGA GGCCAAGAAG 60 CTGCTGTGGC TGATGCGGAT TCAGAAAGGG CTCCCTCATC AGAGACGTGC GACATGTAAA CCAAATTAAA CTATGGTGTC CAAAGATACG CAATC'=AT CCTAGTAATT GTGGTCA'ITG GGTGATGTTG G'ITTGGGCAG GCCATCTCTA ATATCCTI1GA AACACCTTTT TCTGCTCTCC AGGAAGGGGT CAGGGCTGCC ACAGCGGGGC I17GGAGTGC-3- (FRAG. NO:__) (SEQ. ID NO:3011) 5'-GAATTCACAT T[CTCACCTT TTGATGTAFT AAGAAAGTAT GGAGAAATAT ATCCTCTATC AAATTTTCAT 65 GCCT]?CAATA ATTCTAATT CATCAGTCAG TGTITCCA TCCTrTACTG TGATGATGCC CrfCTTrCCA AACTTMCA TTGCATCAGA GATGATGTTA CCAATITCTT TGTCTCCATT TGCAGAAATT GTAGCAACCT WO 00/62736 PCT/USOO/08020 215 GTGCAATTTC TrCAGGTTTG GTCACAGGTT TAGACTGCTT TTTAAGTTCA GCAATTACAG CATCAACAGC TAACATCACA CCTCTCTTGA TTTCCACTGG ATTAGCACCT TTGCTAACCT TCTGGAAGGC TTATTTGGAA ATAGAGCATA CCAGTACAGC AGCAGTGATA GTGCCATCCC CCAGTCTCTC CATTGTGTT ATTGGCAACA TCTTGGACAA GTTTAGCTCC AATGCTTA TATTTATCCT TTAAGTCAAT TGACTTTGCA TCAGTCACAC 5 CATCTTTTGT TACTTTGGGA CTTCCCCAGC TATGTTCAAT AATTACTGTT CTTCCCTTTG GCCCCATTGT AATGGCTACA GCATCGACAA AAAGTCTACA CTTTGAAGCA TTAAGGCTCA GACATCAGCA CCAAATTTTA CATCTTTACC ATCACTTCAA GTGAGGTGAG GAGCCAGTAG CCTGGACACT GGTCTCATCT GGTGAAAGAC TGTGGGTAAT GGAAGCATTT CTGTGGGGTG GTGGCAGGAC ATGTGCATGG TGAGGCAGGT CATCAGCAGC AAGTGAGAGC TGCCTCTAC TTTCTAAAGG TGACATAGCA AGTATACAAA AAAAAATAAA ATATTAATTT 10 AGGCAGAGCA CATAAAGGCT TTATTTCATA TTCCATTTCT CTGTATGCTT TCTTCACCAG GAAGAAATAG TTAGTGTC AGGAATGAAT GAGTCTGCCC CTCAATTCCA GCCTGCTCAG CACACAAGGA AACAAAGCCC TGACAATCAG AGTGACTCCC TGGTGACTAA GCTCCAGTCC TGGATGCATA TTTGTTTAGC AGTTCTGACA GCATCTGACC CAGCCCTCTC TTGCATACC CCACCAGAAC CTTCTTTTTT TrTTTTTC TTTGAGACTG AGTCTTGCTC TGTCGGAAGC GATTCCCGTG CCTCAGCCTC CCAAATACCT GGAATTATAG GCGTAAGCCA 15 TCATGCCTGG CTAATTTG TATTTTCAT GGAGATGGGG TTTGCCATG TTGGTCAAAT TGGTCTCACA CTCCTGACCT CATGTGATCC ACCTGCCTCA GCCTCCCAAA GTGCTGGGAT GACAGGTGTA AGCCACCATG CTAGGCTCAG AAATTTCCTT TTATAAAAAT GTCATTAAGG ATCTTGGCTG CACAATATCG TTACCAGCTT CCTTTAAATC CACCTCTGGC CTGCCAGGAA TCAGGG1CT TCAGAACCTG ACATTTTAAA TGAAGAGGTC AGGCAGGTCA TGAGGAAAGC CTCATTGTCC CCATGTCTCT GTCACTGCTG CACCCCTGAG ACATCACAGA 20 CATGGACACT GGGGCCTGCT TGTTTCTCAA ACTGCCCTTA GATCGAAAGA GGGAGGAACC AGGATGAATG CCACTCATTT TCCCAAGAAA GGCCCTCTCC TGAGTGCCCG GGATGGGGCT CTGTCCATTG CCTGGGGCCG CCAATTGCTA CTCTGGGTTA CGGAAGAAGG ACAGGGTCCT GAGAGACACC AGAGACCTCA CACAGCCCTG AAAACATGGG GCTCCTTCAT AAGTGTTTCC CATCACCAAC AGGGAGACCA CGTGGAGGCC TTGCAGCCCT ACTCGGTGCT TCTCCACCAA ATCCCAAGGG CAGTGACGCT GACGTCTGTG GAAAGCAGAG AAAGCCCTGG 25 CTCCCAAAGC CCTGAAGTCC TGTGGAGCTG ACATTCCCTG AGTGACGGTG TGAATGGAAG GAACTCAAGT GCGGGTGGTA GGCCACCTCC TGGCCCAGGC CTGGGTGAAC TCTGAGGGGA CACATGTAGT CACAATCCCA TCCTCCCATT CTCCTTCTCA GAGGAAGGAA GTGGGCATCC ATCTGCCTCA TCTCTCTCCC GTGGGGAAGA TGGGGAGTTT CAGGGGAACT TTCACATAAA TTTCACCAGC TCAGATCTCC TGTGAGGATG GGGCCCACCA TGCTCCCGGT GCTGCCAGAG GCCCTGAGCC CCTCCAGGGT CCCTGGGTTT GAGCCAGCCC TGTATCATCC 30 CCAGGAGCTG AATGTCCGAA CAATGGATAG AATTAGATGG AAAGAGCTCT CAATTTGGCC TGAGACTGTC CCCAGATACT CAGGAAAAAC AGGACGTCGC ACAGAGTGGG CAGCAGGTGA GTGGCAGGTT ATAGGTCCTG AGTTTGAGTT TGTTCTCACG TGAGACAGAC CCAGCCCCTC ACTCCATTCA CACACTGGGT TTTAAATGGT GCAAGATAGG AGGAATT17C TGGTCCCAAG AGCAGGAGGA AGGGATTTTC TGGGGTTTCC TGAGTCCAGA TTTGCATAAG ATCTCCTGAG TGTGCATTGT TCTTTGAGGA CCATTCTCTG ACTCACCAGG TAAGTGGCTG 35 AATTCTAACC TCTGTAATGA GCATTGCACC CAATACCAGT TCTGAACTCT ACCTGGTGAC CAGGGACCAG GACCTTTATA AGGTGGAAGG CTTGATGTCC TCCCCAGACT CAGCTCCTGG TGAAGCTCCC AGCCATCAGC CATGAGGGTC TTGTATCTCC TCTTCTCGTT CCTCTTCATA TTCCTGATGC CTCTTCCAGG TGAGATGGGC CAGGGAAATA GGAGGGTTGG CCAAATGGAA GAATGGCGTA GAAGTTCTCT GTCTCCTCTC ATTCCCCTCC ACCTATCTCT CCCTCATCCC TCTCTCTCCT TCCTCTCTCT GTGTGTCCCC TCCATCCT TCTCCTGCTT 40 CTCTCTCTTC TTCCCTCTCT CTCTTTYTT CTGTCTTTCT TTTCCTCTC TCCCTAGAGC ATGTCTTTCT TTCTTTCTCT TTCCTTTCTT CTACCCACAC TTTTAGACTG AGTAGACTGA ATGCCCTATT TAATTGAACC AAGCATTGCT TCCTTCAATA GAAAAGGAGT TTGAGAACCC AATGGACAAC TCACTCGTTC TTCTAAGCCA ATATGAAGGA GCCCAGTAGT TTGTAAATAT CATCTCTTCA CTGCTTTCCA TGCTACAACT GCTGAGACTA TGGTTGAAAC CTGTTAGGTG ACTTAAA TAAAAGGCAG AAATTTTGAT TTTATCTAAA GAAAGTAGTA 45 TAGAATGTCA TTTCTAAAT TTTTATATTT AAAGAGTAGA TACTGCAACC TAGAGAATTC CAGATAATCT TAAGGCCCAG CCTATACTGT GAGAACTACT GCAGCAGACA CTCTGCCCCC AGGACTC TGATCAGAGG CCCTGAGAAC AGTCCCTGCC ACTAGGCCAC TGCAGGTTCA CAGGACAGGG ACAGCCCATT GAAACCAACT TTTAAACCTG GATGCCTAAC CTTCATTTTC TCCTTGATAT TATGAAAATA AAATAAAAAC CATGAAAGGA TAAAAGAGGG AGAGTGGAAG GGAAGGATGG AGAAAGGGAA AAAGAAAATT TGAGAGTAAA TCCTAAAACA 50 ATTAATCTAA TAGATATCAT CTTGTGAAAT CCTCATTTTA CCAATCTTAT TTATGAGTCC TGGGTTTTGT GAGAACAATG GGGTTCTGAG AGGCACCAGA GACCTCATAT TTTCCAAAAC CTAGAACAGT ATAATGAAGG AAGGAGGGAA GGAGGGAGGG AGGGAGGGAA GGAGGGAAGG AGGGAGGGAG GGAGGGAAAC AAAAAGAAGA ATGAGGTTGA AACCAGGACT TAGATATTAG AAACAAGCCA TTACAAAATT TATTTCTATG GTTAATTGTG GTTTCAACT GTAAGTTACT TGGTGTTAAT TTCCTATTAA ACAATTTCAG TAAGTTGCAT 55 CTTTTATC CCATCTCAGA TCAAATACTT AACAGACTAA ATGATTTGAA AAAGCAAAAG TTTACTGGCT TGTGTGTGTT AAAATGGAGG TATGGTGGCT TTGATATTAT CTTCT7GTGG TGGAGCTGAA TTCACAAGAG ATCGTTGCTG AGCTCCTGCC AGACCCCACC TGGAGGCCCC AGTCACTCAG GAGAGATCAG GGTCTTTCAC AATCAGGTTC TACAAAAATA AACATCCCCC AAACCACAGC AGTGCCAGTT TCCATGTCAG AAACTTAGAT CCAAATGACT GACTCGCGTC TCATTATCAT GATGGAAAAG CCCAGGCTTG AGAAAGAAGC CCGCTGCGGA 60 TTTACTCAAG GCGATACTGA CACAGGGTTT GTGTTTTTCC AACATGAGTT TTGAGTTCTr ACACGCTGTT TGCTCTTTTT GTGTGTT TCCCTGTTAG GTGTITTTGG TGGTATAGGC GATCCTGTTA CCTGCCTTAA GAGTGGAGCC ATATGTCATC CAGTCTTTTG CCCTAGAAGG TATAAACAAA TTGGCACCTG TGGTCTCCCT GGAACAAAAT GCTGCAAAAA GCCATGAGGA GGCCAAGAAG CTGCTGTGGC TGATGCGGAT TCAGAAAGGG CTCCCTCATC AGAGACGTGC GACATGTAAA CCAAATTAAA CTATGGTGTC CAAAGATACG CAATCTTTAT 65 CCTAGTAATT GTGGTCATTG GGTGATGTTG GTTTGGGCAG GCCATCTCTA ATATCCT7GA AACACCTTTT TCTGCTCTCC AGGAAGGGGT CAGGGCTGCC ACAGCGGGGC TTGGAGTGC-3' (FRAG. NO:__) (SEQ. ID WO 00/62736 PCT/USOO/08020 216 NO:2476) 5'-ATCCTTTAAG TCAATGGACT TTGCATCAGT CACACCATCT MGTFTACTT TGGACTrCCC CAGCTATGTr CAATAATTAC TGTrCTTCCC 'ITGGGCCCCA 'FrGTAATGGC TACAGCCTCG ACAAAAAGTC TACAC=TGA AGCATTAAGG CTCGGACATC AGCACCAAAT TTTACATCTT TACCATCACT TCAAGTGAGG TGAGGAGCCA 5 GTAGCCTGGA CACTGGTCTC ATCTGGTGAA AGACTGTGGG TAATGGAAGC A'IMrCTGTGG GGTGCTGGCA GGACATGTGC ATGGCGAGGC AGGTCATCAG CAGCAAGTGA GAGCTGCCTC TTACT]TCTA AAGGTGACAT AGCAAATATA CAAAAAAAAA TAAATAAATI' A1TAATTTAG GTAGAGCACA TAAAGGCTIT A'IMCATA'TT CCATTTCTCT GTATGCTTTC 'FrCACCAGGA AGAAATAGITr FAGTGTCAG GAATGAATGA GTCTGCCCCT CAATTCCAGG CTGCTCAACA CACAAGGAAA CAAAGCCCTG ACAATCAGAG TGACTCCCTG GTGACTAAGC 10 TCCCAGTCCT GGATGCATAT TTGTMAGCA GTT1CTGACAG CATITGACCC AGCCCTCTCT CTGCATATCC CATCAGAACC TTCTTTM7 TITfT=CTT TGAGACTGAG TCTTGCTCTG TCGGAAGCGA CTCCTGTGCC TCAGCCTCCC AAATACCTGG AA'ITATAGGC GTAAGCCATC ATGCCTGGCT AATITITGTA Tr'TrCATGG AGATGGGGT'T TrGCCATGTT GGTCAAATTG GTCTCACACT CCTGACCTCA TGTGATCCAC CTGCCTCAGC CTCCCAAACT GCTGGGATGA CAGGTGTAAG CCACCATGCT AGGCTCAGAA A'ITTCCTrTT ATAAAAATGT 15 CA'I1AAGGAT CTTGGCTGCA CAATATCG'IT ACCAGCTTCC TTTAAATCCA CI17CTGGCCT GCCAGGAATC AGGTTCTI'CA GAACCTGACA TITAAATGA AGAGGTCAGG CAGTTCATGA GGAAAGCCTC ATTGTCCCCA TGTCTCTGTC ACTGCTGCAC CCCTGAGACA TCACAGACAT GGACACTGGG GCCTGCTTGT TTCTCAAACT GCCCTAGAT CGAAAGAGGG AGGAACCAGG ATGAATGCCA CTCATICC CAAGAAAGGC CCTCTCCTGA GTGCCCGGGA TGGGGCTCTG TCCATTGCCT GGGGCCGCCA ATTGCTACTC TGGG'ITACGG AGGAAGGACA 20 GGGTCCTGAG AGACACCAGA GACCTCACAC AGCCCTGAAA ACATGGGGCT CCTTCATAAG TG'L=CCCAT CACCAACAGG GAGACCACGT GGAGGCC ITG CAGCCCCACT CGGTGCTTCT CCACCAAATC CCAAGGGCAG TGACGCTGAC GTCTGTGGAA AGCAGAGAAA GCCCTGGCTC CCAAAGCCCT GAAGTCCCTG TGGAGCTGAC ATrTCCCTGAG TGACGGTGTG AATGGAAGGA ACTCAAGTGC GGGTGGTAGG CCACCTCCTG GCCCAGGCCT GGGTGAACTC TGAGGGGACA CATGTAGTCA CAATCCCATC CTCCCATrCT CCT7CTCAGA GGAAGGAAGT 25 GGGCATCCAT CTGCCTCATC TCTCTCCCGT GGGGAAGATG GGGAGTCA GGGGAA=T1 CACATAAATT TCACCAGCTC AGATCTCCTG TGAGGATGGG GCCCACCATG CTCCCGGTGC TGCCAGAGGC CCTGAGCCCC TCCCAGGGTC CCTGGGTITG AGCCAGCCCT GTATCATCCC CAGGAGCTGA ATGTCAGAGC AATGGATAGA ATTAGATGGA AAGAGCTCTC AATI17GACCT GAGACTGTCC CCAGATACTC AGGAAAAACA GGACGTCGCA CAGAGTGGGC AGCAGGTGAG TGGCAGG1TA TAGGTCCTGA GTGAGTT GTTCTCACGT GAGACAGACC 30 CAGCCCCTCA CTCCATTCAC ACACTGGGTT TTAAATGGTG CAAGATAGGA GCAAT=CT GGTCCCAAGA GCAGGAGGAA GGGATTCT GGGG'IMCCT GAGTCCAGAT 'I1GCATAAGA TCTCCTGAGT GTGCATTGTT C'ITTGAGGAC CArrCTCTGA CTCACCAGGT AAGTGGCTGA ATTCTAACCT CTGTAATGAG CATTGCACCC AATACCAGTT CTGAACTCTA CCTGGTGACC AGGGACCAGG ACCTTTATAA GGTGGAAGGC FTGATGTCCT CCCCAGACTC AGCTCCTGGT GAAGCTCCCA GCCATCAGCC ATGAGGGTCT TGTATCTCCT CTTCTCGTTC 35 CTCTTCATAT TCCTGATGCC TCTrCCAGGT GAGATGGGCC AGGGAAATAG GAGGGTTGGC CAAATGGAAG AATGGCGTAG AAGTTCTCTG TCTCCTCTCA TTCCCCTCCA CCTATCTCTC CCTCATCCCT CTCTCTCCTT CCTCTCTCTG TGTGTCCCCT CCATCCTIT CTCCTGCTTC TCTCT=TCT TCCCTCTCTC TCTITI'TCT GTC'rC=~ TTCCTCTCTC CCTAGAGCAT GTCTECTI1 Cn7ICTC'T CCT7CTTCT ACCCACACT-F TTAGACTGAA TGCCCTA'IT AATTGAACAA AGCATfGCTT CCTTCAATAG AAAAGGAGTT TGAGAACCCA 40 ATGGACACCT CACTCGTTCT TCTAAGCCAA TATGAAGGAG CCCAGTAGCT TGTAAATATC ATCTCTTCAC TGC'TTrCCAT GCTACAACTG CTGAGACTAT GGTTGAAACC TG~~rAGGTGA CTITIAAAT AAAAGGCAGA AAY1TGATT TTATCTAAAG AAAGTAGTAT AGAATGTCAT 'T-FCTAAATT TTATATITA AAGGGTAGAT ACTGCAACCT AGAGAA'rTCC AGATAATCT AAGGCCCAGC CTATACTGTG AGAACTACTG CAGCAAGACA CTCTGCCTCC AGGACTInrC TGATCAGAGG CCCTGAGAAC AGTCCCTGCC ACTAGGCCAC TGCAGGTTCA 45 CAGGACAGGG TACAGCCCAT TGAAACCTAC T1TAAACCT GGATGCCTAA CCTfCAT=f CTC=~GATA 1TATGAAAAT AAAATAAAAA CCATGAAAGG ATAAAAGAGG GAGAGTGGAA GGGAAGGATG GAGAAAGGGA AAAAGAAAAT TTGAGAGTAA ATCCTAAAAC AATTAATCTA ATAGATATCA TCYI'GTGAAA TCCTCATrTI ACCAATCTTA TTATGAGTC CTGGGYVVG TGAGAACAAT GGGGTTCTGA GAGGCACCAG AGACCTCATG TLTCCAAAA CCTAGAACAG TATAATGAAG GAAGGCGGGG AGGCAGGGAG GCAGGGAGGC AGGGAGGCAG 50 GGAGGCGGGC AGGTGGGGAG GGAGGGACGG AAGGAGGGAG GGAGGGAGGG AGGGAGGGAG GGAGGGATAA AAAAAGAAGA ATGAGGTTGA AACCAGGACT TAGATATrAG AAACAAGCCA TTACAAAATF[ TA'ITCTATG GTTAAT'fGTG G TTTCAACT GTAAGTTACT TGGTGT7AAT TTCCTATrAA ACAA ITTCAG TAAGTTGCAT CTITTATCC CATCTCAGGT CAAATACTTA ACAGACTAAA TGAYITGAAA AAGCAAAAGT TTACTGGCTT GTGTGTGTTrA AAATGGAGGT ATGGTGGCTF TGATATTATC TI'T=GTGGT GGAGCTGAAT TCACAAGAGA 55 TCGTTGCTGA GCTCCTACCA GACCCCACCT GGAGGCCCCA GTCACTCAGG AGAGATCAGG GTCTPTCACA ATCAGGTTCT ACAAAAATAA ACATCCCCCC AACCACAGCA GTGCCAG'IT CCATGTCAGA AACTTAGATC CAAATGACTG ACTCGCGTCT CATFATCATG ATGGAAAAGC CCAGGCTrGA GAAAGAAGCC CGCTGCGGAT TTACTCAAGG CGATACTGAC ACAGGG FITG TGTT=CCA ACATGAG'IM TGAGTTCTTA CACGCTGTI17 GCTC1ITMG TGTGTr=1T CCCTGTTAGG TGTTIGGT GGTATAGGCG ATCCTGTTAC CTGCCTTAAG 60 AGTGGAGCCA TATGTCATCC AGTC=LGC CCTAGAAGGT ATAAACAAAT TGGCACCTGT GGTCTCCCTG GAACAAAATG CTGCAAAAAG CCATGAGGAG GCCAAGAAGC TGCTGTGGCT GATGCGGATT CAGAAAGGGC TCCCTCATCA GAGACGTGCG ACATGTAAAC CAAATrAAAC TATGGTGTCC AAAGATACGC AATCTrATC CTAGTAATTG TGGTCATTGG GTGATGTTGG 1TTTGGGCAGG CCATCTCTAA TATCCTTGAA ACACCTI17 CTGCTCTCCA GGAAGGGGTC AGGGCTGCCA CAGCGGGGCT TGGAGTG=T TCCAGGGTCA CAGGCATCTG 65 TATTCTITGG ATrCCTTGAC CTTCCCCAI7 TATT1CCCGGC AT=TCCTAA AACGTGTGCT TTGCTCCTCC TGCATCCTCC CCTTGCATGC CCTCACCTAC CCCACATCTT CCCTAAAAAA AGCAAGCCCA ACTCAAAGAC WO 00/62736 PCT/USOO/08020 217 CAGTTCCCTC ATGGAATCAT AGTGGATCTG CCAAGGGAGG GGATGCCCAG TCCTCTGTTC TTCACAAGAC TCCCTTCTTC TGGCTAAGGT TTCTTATGCA ATTAT GAATTCCCTG TAAGCCCTGT TACAGGGGCT GCACCCCAGA TACAACCTGA CCTGTGTCCA AGGCGGGCAA CTCAACCCTT AGATATTGAA TGGGTCCCAT GGCACCAATG CTTAAACACC AGCAGCCCTC ACAACCACAG ATCGTGTT AAGGATGAGG AGGTAGTTCT 5 CTGGATGCAC AGGCTTCAAT CCAAATGGGC TCATGACGCC GCAGCACACA CCCAGTCTGC AGCCTGAAGA GTTGGAGCAT TGCATTCACA GAAAGCATCC AGACATGATC ATGGGCTCAG GGATACACCT GTrCTCCGAT GTGTACCAGT GAAGGATGGA AACTCCTATG CCTCCCAGAA AGCACCACTC AAGCTTTTGC TGAATGCTTC TCTGAAGGCC CACAAGGCTG AGAGGCTGTG CAACACCAGC AGTAAAGTGA ATGCCCAGAC TCCCACCTCC TTCTTGGGT GGCCATCTGG AAAGGCCACT CCCACCCTGA TGGCTAATGC CTCAGACCAG TTCTTGGCCC 10 AGATGATCCT AGACAATTGT TTAAGCTTAA ACTGTTCATT GGCCAAGCAA ACAGGTGATA GTACCTCTGG GGAACCACAT GCCGCGTGTA CATCCAGATC TCAGGAGAAC CCAAAAATGT CTGTTCCACA TAGCAACAGA AGCCCAGGTA GCACTCAGTC TCACCTGGGT GTTCTCCAAC ATCCCAGCTC AGCCAAATGG CTTTCATTAG TITTATGGT TAGACCCCAG GTCCTCGGGA CACTGCTTA GAAACACATT CCAAATCCTC CTCTGTGTGC AGGTGGCATT CCTATCCCAA TCTCTTTGCA GGGCGTATAC TGTGATACGC AGCCAGGCTG TCCCAGAGGC 15 CTTAAATATT CCCTTGGTGC AGGTAGTTCA GCTTAGCCAC AGCCAATGCA TCACAGGGTC AACTGTGTTA GGAGCCATTG AGAATCCATA GTTGGTTGCT GCCTGGGCCT GGCCAGGGCT GACCAAGGTA GATGAGAGGT TCCTCTGTGG AGTTCTACTT TAACCTCACC TTCCCACCAA ATTTCTCAAC TGTCCTTGCC ACCACAATTA TTTAATGGAC CCAACAGAAA GTAACCCCGG AAATTAGGAC ACCTCATCCC AAAAGACCTT TAAATAGGGG AAGTCCACTT GTGCACGGCT GCTCCTTGCT ATAGAAGACC TGGGACAGAG GACTGCTGTC TGCCCTCTCT 20 GGTCACCCTG CCTAGCTAGA GGATCTGTAA GTACTACAAA ACTTAAACTT TACACTGAGT TTTCATCATT GAAGCTATGC CTCCAATCTG ACCTCTGACT GTGGGGCCGC CCCAGAGGGA CCCAGCGGGT GAATCCCTGC TAGGAACGTC TGTCCGGACC TCTGGTGACT GCTGGGGACG ATGGCTTCCA GCTAACTTAA TAGAGAAACT CAAGCAGTTT CCT7CTAAAT ACACATGTCA CATGTCCTGG TTGACATGTC CAGTAAGAAG ACTATCACAG GTCTTTGGAA CATTCTTTTG AGAGAAACCT ATAGGTCC TrGGTCTGTT TTCAATCAG GTTGTTTGAT 25 TTTTGCTATT GAGTTGTTGG AATTCCTTAT GTATTCAGAT ATTTGCCCCT TCTGCCATGT AGGTTTTGCA AATATTTTCT CTCATTCT GGGTTATCTT TTCACTCGGT TGATTGTTTC CTGCTGTG CAGATGCTTT AGCGTTAAAT GAAGCCACAC TTGTCTATTT TCCCTTTTAT TGCCTGTGCC TrTGGTGTCA TAGCCAAGAA ATCATTACCT ACATCAATGT CAAAAGCTTT ATCCTTCTAT ACACTTCTAG TAGTTTATGG TTTCAGTTGT TACATTTAGG TTTTCAATTC ATTCTGAGTT GATGTTCCTA CATGGTGTGA GATAAAGATT TAAATACATA 30 CATATATAAA ATCATGAGGT AGTGTACACT ATAAATATAC AATTGTTAAT TGTTACTCAA GTCTAAGTAG AGGTGGAAAT AATAAACTTT CTTTTTrA CTTAAACCAC TCTGTGTCAC TGAGCTGATT TCACCTTAG CCTGATAAAA TCATTGTCCT CTCCACCCTG ATTCCTACAG GAGACTACTC ACCCCATAAC CTCAAAAACC TCTTCATGAG GATGGTAAGT CACCTGAATC CTGAAGTGAA TTACTCGCTA TTCCATTGGA ACTCATATAG GACACCAGAA TCTAGACCTC CAGAGAACAG CAGGACCCAT CTTCAGAAAA TAAGAAGCAT TTGTTCCCTG 35 AGCCTGTTGA ATCAAAGTGC AATTTCTATT CTTGGAA TGTTAAAAAG TGAATCATAA TATTTAAGCA GGTGAACCCA CGAGTAACAT AGCAGGGTCT TTCTTGTCAT TATTAGCTCC AACCTAGCAC AGACATTAAA GGTACAGATG TATACTAGCA TGAAACTGGG AGAACAGGAG CATTCGAGCA ACCTTGAGAC CAATGGGCCT CTCTTATAAA ATGCACACCT CCTCTCACTG AGATTGAGGA AGGTTFCTTG TCTCCGAGCC TTCTCCCAGT AGAGCTATAA ATCCAGGCTG GCTCCTCCCT CCCCACACAG CTGCTCCTGC TCTCCCTCCT CCAGGTGACC 40 CCAGCCATGA GGACCCTCGC CATCCTTGCT GCCATTCTCC TGGTGGCCCT GCAGGCCCAG GCTGAGCCAC TCCAGGCAAG AGCTGATGAG GTTGCTGCAG CCCCGGAGCA GATTGCAGCG GACATCCCAG AAGTGGTTGT TTCCCTTGCA TGGGACGAAA GCTTGGCTCC AAAGCATCCA GGTGAGAGAG GCAGGCATGC AGAGCTGCTA AGTCTAGAGG GAAGGACGGG AGAGAGGTTC CAGAGTTGGG TCTCAGCAGT CTATGTCACT GAGGTGGCTT CACTTAGAAT CTCTGGGCAT TGATTCTC ATCTAGAAAT TGAACAGAGA GCCAAATAAA CCTGAGAAAC 45 TTTATTCTC CAAAGACTTG ATTCCAAGAA ACATCTGTGA AATTCACTAA GTAAGATA TGAAGAGACA GACTAGTTAT TTCTGGATCT AAACAAGTAG ACTTAGTTGT AAAGAGAACA TTTTACTCTA TCTACAGAAG AGCTAAA AACTGCAGCC AAGCCTGAGG GTAAGTTCAG GTGTGTGTGT GATGGGGCAG GAATGCAAAA ATGAGAGCAA AGGAGAATGA GTCTCAAATT CTGTGTGACA AGCACTGCTC TGCGTGTTTA TTCCTATCGA CTGAGGTTGT TCGTGCTACC GGCTGCAATG CAGCCAGCAT CACCTGTCAG CTAGCATGTG ACTTICCCCGA 50 GATTCTTTTT CTTACCCACT GCTAACTCCA TACTCAATTT CTCATGCTCT CCCTGTCCCA GGCTCAAGGA AAAACATGGA CTGCTATTGC AGAATACCAG CGTGCATTGC AGGAGAACGT CGCTATGGAA CCTGCATCTA CCAGGGAAGA CTCTGGGCAT TCTGCTGCTG AGCTTGCAGA AAAAGAAAAA TGAGCTCAAA ATTTGCTTTG AGAGCTACAG GGAATTGCTA TTACTCCTGT ACCTTCTGCT CAATTTCCTT TCCTCATCTC AAATAAATGC CTTGTTACAA GATTTCTGTG TTTCCACCTC TTTAATGTGT GATATGTGTC TGTGTCAAGA CACTTGGGAT 55 ACACGTACCA AAACGCAAAA TCAAATT GAACAATATA-3' (FRAG. NO:_) (SEQ. ID NO:3012) Human Defensin 3 Nucleic Acid and Antisense Oligonucleotide Fragments 5'-CGCTGCBBTC TGCTCCGGGG CTGCBGCBBC CTCBTCBGCTC TTGCCTGGBGTG GCTCBGCCTGG GCCTGCBGGG CCBCCBGGBGB BTGGCBGCBBG GBTGGCGBGGG TCCTCBTGGC TGGGGTCBCCT GGBGGBGGGB GBGCBGGGGG TCCTCBTGGC TGGGGTCCCT CTCTCCCGTC CT CCTACCTTGC TATAGAAGAC 60 CTGGGACAGA GGACTGCTGT CTGCCCTCTC TGGTCACCCT GCCTAGCTAG AGGATCTGTG ACCCCAGCCA TGAGGACCCT CGCCATCCTT GCTGCCATTC TCCTGGTGGC CCTGCAGGCC CAGGCTGAGC CACTCCAGGC AAGAGCTGAT GAGGTTGCTG CAGCCCCGGA GCAGATTGCA GCGGACATCC CAGAAGTGGT TGTTTCCCTT GCATGGGACG AAAGCTTGGC TCCAAAGCAT CCAGGCTCAA GGAAAAACAT GGACTGCTAT TGCAGAATAC CAGCGTGCAT TGCAGGAGAA CGTCGCTATG GAACCTGCAT CTACCAGGGA AGACTCTGGG CATTCTGCTG 65 CTGAGCTTGC AGAAAAAGAA AAATGAGCTC AAAATTTGCT TTGAGAGCTA CAGGGAATTG CTATTACTCC WO 00/62736 PCT/USOO/08020 218 TGTACCTrCT GCTCAATIT7C CTTT-3' (FRAG. NO:1804) (SEQ. ID NO:3013) 5'-CCTACCTTGC TATAGAAGAC CTGGGACAGA GGACTGCTGT CTGCCCTCTC TGGTCACCCT GCCTAGCTAG AGGATCTGTG ACCCCAGCCA TGAGGACCCT CGCCATCCTT GCTGCCATTC TCCTGGTGGC CCTGCAGGCC CAGGCTGAGC CACTCCAGGC AAGAGCTGAT GAGGTTGCTG CAGCCCCGGA GCAGATTGCA GCGGACATCC 5 CAGAAGTGGT TGTTTCCCTT GCATGGGACG AAAGCTTGGC TCCAAAGCAT CCAGGCTCAA GGAAAAACAT GGACTGCTAT TGCAGAATAC CAGCGTGCAT TGCAGGAGAA CGTCGCTATG GAACCTGCAT CTACCAGGGA AGACTCTGGG CATTCTGCTG CTGAGCTTGC AGAAAAAGAA AAATGAGCTC AAAATTTGCT TTGAGAGCTA CAGGGAATTG CTATTACTCC TGTACCTrCT GCTCAAT'ITTC CTTT-3' (FRAG. NO:_) (SEQ. ID NO:2478) 5'-GAATTCCCTG TAAGCCCTGT TACAGGGGCT GCACCCCAGA TACAACCTGA CCTGTGTCCA AGGCGGGCAA 10 CTCAACCCTT AGATATTGAA TGGGTCCCAT GGCACCAATG CTAAACACC AGCAGCCCTC ACAACCACAG ATCGTGTT AAGGATGAGG AGGTAGTTCT CTGGATGCAC AGGCTTCAAT CCAAATGGGC TCATGACGCC GCAGCACACA CCCAGTCTGC AGCCTGAAGA GTTGGAGCAT TGCATTCACA GAAAGCATCC AGACATGATC ATGGGCTCAG GGATACACCT GTTCTCCGAT GTGTACCAGT GAAGGATGGA AACTCCTATG CCTCCCAGAA AGCACCACTC AAGCTTGC TGAATGCTTC TCTGAAGGCC CACAAGGCTG AGAGGCTGTG CAACACCAGC 15 AGTAAAGTGA ATGCCCAGAC TCCCACCTCC TTTCTTGGGT GGCCATCTGG AAAGGCCACT CCCACCCTGA TGGCTAATGC CTCAGACCAG TTCTTGGCCC AGATGATCCT AGACAATTGT TTAAGCTTAA ACTGTTCATT GGCCAAGCAA ACAGGTGATA GTACCTCTGG GGAACCACAT GCCGCGTGTA CATCCAGATC TCAGGAGAAC CCAAAAATGT CTGTTCCACA TAGCAACAGA AGCCCAGGTA GCACTCAGTC TCACCTGGGT GTTCTCCAAC ATCCCAGCTC AGCCAAATGG CTTCATTAG TTTTATGGT TAGACCCCAG GTCCTCGGGA CACTGCTTTA 20 GAAACACATT CCAAATCCTC CTCTGTGTGC AGGTGGCATT CCTATCCCAA TCTCTTTGCA GGGCGTATAC TGTGATACGC AGCCAGGCTG TCCCAGAGGC CTTAAATATT CCCTTGGTGC AGGTAGTTCA GCTTAGCCAC AGCCAATGCA TCACAGGGTC AACTGTGTTA GGAGCCATTG AGAATCCATA GTTGGTTGCT GCCTGGGCCT GGCCAGGGCT GACCAAGGTA GATGAGAGGT TCCTCTGTGG AGTrCTACTT TAACCTCACC TTCCCACCAA ATTTCTCAAC TGTCCTTGCC ACCACAATTA TTTAATGGAC CCAACAGAAA GTAACCCCGG AAATTAGGAC 25 ACCTCATCCC AAAAGACCTT TAAATAGGGG AAGTCCACTT GTGCACGGCT GCTCCTTGCT ATAGAAGACC TGGGACAGAG GACTGCTGTC TGCCCTCTCT GGTCACCCTG CCTAGCTAGA GGATCTGTAA GTACTACAAA ACTTAAACTT TACACTGAGT TTTCATCATT GAAGCTATGC CTCCAATCTG ACCTCTGACT GTGGGGCCGC CCCAGAGGGA CCCAGCGGGT GAATCCCTGC TAGGAACGTC TGTCCGGACC TCTGGTGACT GCTGGGGACG ATGGCTTCCA GCTAACTTAA TAGAGAAACT CAAGCAGTT CCTTCTAAAT ACACATGTCA CATGTCCTGG 30 TTGACATGTC CAGTAAGAAG ACTATCACAG GTCTTGGAA CATTCTITTG AGAGAAACCT ATTTAGGTCC TTGGTCTGTT TTTCAATCAG GTTGTTTGAT TTTGCTATT GAGTTGTTGG AATTCCTTAT GTATTCAGAT ATTTGCCCCT TCTGCCATGT AGGTTTGCA AATATTTTCT CTCATTTTCT GGGTTATCTT TTCACTCGGT TGATTGTTTC CTGCTGTG CAGATGCTTT AGCGTTAAAT GAAGCCACAC TTGTCTATT TCCCTTAT TGCCTGTGCC TTTGGTGTCA TAGCCAAGAA ATCATTACCT ACATCAATGT CAAAAGCTTT ATCCTTCTAT 35 ACACTTCTAG TAGTTTATGG TTTCAGTTGT TACATAGG TTTTCAATTC ArCTGAGTT GATGTTCCTA CATGGTGTGA GATAAAGATT TAAATACATA CATATATAAA ATCATGAGGT AGTGTACACT ATAAATATAC AATTGTTAAT TGTTACTCAA GTCTAAGTAG AGGTGGAAAT AATAAACTTT CITTTTTA CTTAAACCAC TCTGTGTCAC TGAGCTGATT TCACCTTTAG CCTGATAAAA TCATTGTCCT CTCCACCCTG ATTCCTACAG GAGACTACTC ACCCCATAAC CTCAAAAACC TCTTCATGAG GATGGTAAGT CACCTGAATC CTGAAGTGAA 40 TTACTCGCTA TTCCATTGGA ACTCATATAG GACACCAGAA TCTAGACCTC CAGAGAACAG CAGGACCCAT CTTCAGAAAA TAAGAAGCAT TTGTTCCCTG AGCCTGTTGA ATCAAAGTGC AATTTCTATT CTTTTGGAA TGTTAAAAAG TGAATCATAA TATTTAAGCA GGTGAACCCA CGAGTAACAT AGCAGGGTCT TTCTTGTCAT TATTAGCTCC AACCTAGCAC AGACATTAAA GGTACAGATG TATACTAGCA TGAAACTGGG AGAACAGGAG CATTCGAGCA ACCTTGAGAC CAATGGGCCT CTCTTATAAA ATGCACACCT CCTCTCACTG AGATTGAGGA 45 AGGTTCTTG TCTCCGAGCC TTCTCCCAGT AGAGCTATAA ATCCAGGCTG GCTCCTCCCT CCCCACACAG CTGCTCCTGC TCTCCCTCCT CCAGGTGACC CCAGCCATGA GGACCCTCGC CATCCTTGCT GCCATTCTCC TGGTGGCCCT GCAGGCCCAG GCTGAGCCAC TCCAGGCAAG AGCTGATGAG GTTGCTGCAG CCCCGGAGCA GATTGCAGCG GACATCCCAG AAGTGGTTGT TTCCCTTGCA TGGGACGAAA GCTTGGCTCC AAAGCATCCA GGTGAGAGAG GCAGGCATGC AGAGCTGCTA AGTCTAGAGG GAAGGACGGG AGAGAGGTTC CAGAGTTGGG 50 TCTCAGCAGT CTATGTCACT GAGGTGGCTT CACTTAGAAT CTCTGGGCAT TGATTTTCTC ATCTAGAAAT TGAACAGAGA GCCAAATAAA CCTGAGAAAC TTTATTTCTC CAAAGACTTG ATTCCAAGAA ACATCTGTGA AATTCACTAA GTTTAAGATA TGAAGAGACA GACTAGTTAT TTCTGGATCT AAACAAGTAG ACTTAGTTGT AAAGAGAACA TTTACTCTA TCTACAGAAG AGCTTTAAA AACTGCAGCC AAGCCTGAGG GTAAGTTCAG GTGTGTGTGT GATGGGGCAG GAATGCAAAA ATGAGAGCAA AGGAGAATGA GTCTCAAATT CTGTGTGACA 55 AGCACTGCTC TGCGTGTTTA TTCCTATCGA CTGAGGTTGT TCGTGCTACC GGCTGCAATG CAGCCAGCAT CACCTGTCAG CTAGCATGTG ACTTCCCCGA GATTCTTT CTTACCCACT GCTAACTCCA TACTCAATTT CTCATGCTCT CCCTGTCCCA GGCTCAAGGA AAAACATGGA CTGCTATTGC AGAATACCAG CGTGCATTGC AGGAGAACGT CGCTATGGAA CCTGCATCTA CCAGGGAAGA CTCTGGGCAT TCTGCTGCTG AGCTTGCAGA AAAAGAAAAA TGAGCTCAAA ATTTGCTTTG AGAGCTACAG GGAATTGCTA TTACTCCTGT ACCTTCTGCT 60 CAATTTCCTT TCCTCATCTC AAATAAATGC CTTGTTACAA GATTTCTGTG TTTCCACCTC TTTAATGTGT GATATGTGTC TGTGTCAAGA CACTTGGGAT ACACGTACCA AAACGCAAAA TCAAATTTTT GAACAATATA-3' (FRAG. NO:_) (SEQ. ID NO:2477) 5'-GGCBGCBBGG-3' (FRAG. NO:1805) (SEQ. ID NO:1818) 5'-GG CTG GGG-3' (FRAG. NO:1806) (SEQ. ID NO:1819) 65 5'-GGGGTCBCC-3' (FRAG. NO:1807) (SEQ. ID NO:1820) 5'-GGG TCC TCB TGG CTG GGG TC-3' (FRAG. NO:1216) (SEQ. ID NO:1225) WO 00/62736 PCT/USOO/08020 219 5'-CCT CTC TCC CGT CCT-3' (FRAG. NO:1217) (SEQ. ID NO:1226) 5'-CGCTGCBBTC TGCTCCGGGG CTGCBGCBBC CTCBTCBGCTC TTGCCTGGBGTG GCTCBGCCTGG GCCTGCBGGG CCBCCBGGBGB BTGGCBGCBBG GBTGGCGBGGG TCCTCBTGGC TGGGGTCBCCT GGBGGBGGGB GBGCBGG-3' (FRAG. NO:1808) (SEQ. ID NO:1821) 5 Human Macrophage Inflammatory Protein-1-alpha/RANTES Receptor Nucleic Acid and Antisense Oligonucleotide Fragments 5'-GTCTTTGTTT CTGGGCTCGT GCCCCBTCCC GGCTTCTCTC TGGTTCCGTC CTCTGTGGTG TTTGGCCCTG CTTCCTTG CCTGTTGAGG GGGCAGCAGT TGGGCCCCAA AGGCCCTCTC GTTCACCTTC TGGCACGGAGTT GCATCCCCATA GTCAAACTCT GTGGTCGTGT CATAGTCCTC TGTGGTGTTT GGAGTTTCCA TCCCGGCTTC 10 TCTCTGGT-TC CAAGGGAGB GGGGGCBGCB GTTGGGCCCC BBBGGCCCTC TCGTTCBCCT TCTGGCBCGG BGTTGCBTCC CCBTBGTCBB BCTCTGTGGT CGTGTCBTBG TCCTCTGTGG TGTTTGGBGT TTCCBTCCCG GCTTCTCTCT GGTTCCBBGG GB-3' (FRAG. NO:1809) (SEQ. ID NO:1822) 5'-GGGCC CC-3' (FRAG. NO:1810) (SEQ. ID NO:1823) 5'-GGGGGCBGC-3' (FRAG. NO:1811) (SEQ. ID NO:1824) 15 5'-CCCGGCTTC-3' (FRAG. NO:1812) (SEQ. ID NO:1825) 5'-GTC TTT GTT TCT GGG CTC GTG CC-3' (FRAG. NO:1218) (SEQ. ID NO:1227) 5'-CCB TCC CGG CTT CTC TCT GGT TCC-3' (FRAG. NO:1219) (SEQ. ID NO:1228) 5'-GTC CTCTGT GGT GTT TGG-3' (FRAG. NO:1220) (SEQ. ID NO:1229) 5'-CCC TGC TTC CTT TTG CCT GTT-3' (FRAG. NO:1221) (SEQ. ID NO:1230) 20 5'-GAGGGGGCAG CAGTTGGGCC CCAAAGGCCC TCTCGTTCAC CTTCTGGCAC GGAGTGCAT CCCCATAGTC AAACTCTGTG GTCGT-3' (FRAG. NO:1222) (SEQ. ID NO:1231) 5'-GTCATAGTCCTCTGTGGTGTTTGGAGTTTCCATCCCGGCTTCTCTCTGGTTCCAAGGGA-3' (FRAG.NO:1223)(SEQ.ID NO:1232) 5'-GBGGGGGCBG CBGTTGGGCC CCBBBGGCCC TCTCGTTCBC CTTCTGGCBC GGBGTTGCBT CCCCBTBGTC 25 BBBCTCTGTG GTCGTG-3' (FRAG. NO:1224) (SEQ. ID NO:1233) 5'-TCBTBGTCCTCTGTGGTGiTTGGBGTTTCCBTCCCGGCTTCTCTCTGGTTCCBBGGGB-3'(FRAG. NO:1225)(SEQ. ID NO:1234) RANTES Antisense Oligonucleotide Fragments 5'-GGGCBCGGGG CBGTGGGCGG GCBBTGTBGG CBBBGCBGCB GGGTGTGGTG TCCGBGGBBT BTGGGGBGGC 30 BGBTGCBGGB GCGCBGBGGG CBGTBGCBBT GBGGBTGBCB GCGBGGCGTG CCGCGGBGBC CTTCBTGGTB CCTGTGGBGB GGCTGTCGGB GGGGGTGTGG TGTCCGCTTG GCGGTTCTITT CGGGTGTTTC TTCTCTGGGT TGGCCTGCTG CTCGTCGTGGT CGCTCCGCTC CCGGGTTCGT CTCGCTCTGT CGCCCCTTCC TTCCTTIGTCG TGTTCCTCCC TTCCTTGCCT CT-3' (FRAG. NO: 1813) (SEQ. ID NO: 1826) 5'-GGGTTGGC-3' (FRAG. NO: 1814) (SEQ. ID NO: 1827) 35 5'-CGGGG CBG-3' (FRAG. NO: 1815) (SEQ. ID NO: 1828) 5'-CCCGGGTTrCG-3' (FRAG. NO: 1816) (SEQ. ID NO: 1829) 5'-GGGTGTGGTG-3' (FRAG. NO: 1817) (SEQ. ID NO: 1830) 5'-GGGCBCGGGG CBGTGGGCGG GCBBTGTBGG CBBBGCBGCB GGGTGTGGTG TCCGBGGBBT BTGGGGBGGC BGBTGCBGGB GCGC-3' (FRAG. NO:1226) (SEQ. ID NO:1235) 40 5'-BGBGGGCBGTB GCBBTGBGGB TGBCBGCGBG GCGTGCCGCG GBGBCCTTCB TGGTBCCTGT GGBGBGGCTG TCGGBGG-3' (FRAG. NO:1227) (SEQ. ID NO:1236) 5'-GGGTGTGGTGTCCGCTTGGCGGTTC'TTTCGGGTGTrTCTTCTCTGGGTTGGCCTGCTGCTCGTCGTGGTC-3' (FRAG. NO:1228) (SEQ. ID NO:1237) 5'-GCTCCGCTCCCGGG'TCGTCTCGCTCTGTCGCCCCT'rCCTCCTrGTCGTGTTCCTCCCTTCCTTGCCTCT-3' 45 (FRAG. NO:1229) (SEQ. ID NO:1238) 5'-GGGTGTGGTGTCCG-3' (FRAG. NO:1230) (SEQ. ID NO:1239) 5'-CTrGGCGGTTCT1TCGGGTG-3' (FRAG. NO:1231) (SEQ. ID NO:1240) 5'-TTrCTTCTCTGGGTTGGC-3' (FRAG. NO:1232) (SEQ. ID NO:1241) 5'-CTGCTGCTCGTCGTGGTC-3' (FRAG. NO:1233) (SEQ. ID NO:1242) 50 5'-GCTCCGCTCCCGGGTTC-3' (FRAG. NO:1234) (SEQ. ID NO:1243) 5'-GTCTCGCTCTGTCGCCC-3' (FRAG. NO:1235) (SEQ. ID NO:1244) 5'-CTTCCTTCCTTGTC-3' (FRAG. NO:1236) (SEQ. ID NO:1245) 5'-GTGTTCCTCCCTTCCTTGCCTCT-3' (FRAG. NO:1237) (SEQ. ID NO:1246) 5'-GGGCBCGGGG CBGTGGGCGG GCBBTGTBGG CBBBGCBGCB GGGTGTGGTG TCCGBGGBBT BTGGGGBGGC 55 BGBTGCBGGB GCGCBGBGGG CBGTBGCBBT GBGGBTGBCB GCGBGGCGTG CCGCGGBGBC CTTCBTGGTB CCTGTGGBGB GGCTGTCGGB GG-3' (FRAG. NO:1818) (SEQ. ID NO:1831) Human Muscarinic Acetylcholine Receptor HM1* Nucleic Acid and Antisense Oligonucleotide Fragments 5'-GCTGCCCGGC GGGGTGTGCG CTTGGCGCTC CCGTGCTCGG TTCTCTGTCT CCCGGTCCCC CTTGCCTGGC GTCTCGGGCC TTCGTCCTCT TCCTCTTCTT CCTTCCGCTC CGTGGGGGCT GCTTGGTGGG GGCCTGTGCCT 60 CGGGGTCCCG GGGCTTCTGG CCCTTGCCGT TCATGGTGGC TAGGTGGGGC GTTCBTGGTG GCTBGGTGGG GC 3'(FRAG. NO:1819)(SEQ. ID NO: 1832) 5'-GGTGGGGC-3' (FRAG. NO:1820) (SEQ. ID NO: 1833) 5'-GCCCGGCGGGG-3' (FRAG. NO:1821) (SEQ. ID NO: 1834) 5'-CGG GGC TTC TGG CCC-3' (FRAG. NO:1822) (SEQ. ID NO: 1835) WO 00/62736 PCT/USOO/08020 220 5'-GTT CBT GGT GGC TBG GTG GGG C-3' (FRAG. NO:1238) (SEQ. ID NO:1247) 5'-GCT GCC CGG CGG GGT GTG CGC TTG GC-3' (FRAG. NO:1239) (SEQ. ID NO:1248) 5'-GCT CCC GTG CTC GGT TCT CTG TCT CCC GGT-3' (FRAG. NO:1240) (SEQ. ID NO:1249) 5'-CCC CCT TTG CCT GGC GTC TCG G-3' (FRAG. NO:1241) (SEQ. ID NO:1250) 5 5'-GCC TTC GTC CTC TTC CTC TTC TTC CTT CC-3' (FRAG. NO:1242) (SEQ. ID NO:1251) 5'-GCT CCG TGG GGG CTG CTT GGT GGG GGC CTG TGC CTC GGG GTC C-3' (FRAG. NO:1243) (SEQ. ID NO:1252) 5'-CGG GGC TTC TGG CCC TTG CC-3' (FRAG. NO:1244) (SEQ. ID NO:1253) 5'-GTT CAT GGT GGC TAG GTG GGG C-3' (FRAG. NO: 1245) (SEQ. ID NO:1254) 10 Human Muscarinic Acetylcholine Receptor HM3* Nucleic Acid and Antisense Oligonucleotide Fragments 5'-GGG GTG GGT BGG CCG TGT CTG GGGGTT GGC CBT GTT GGT TGC CTCT TGG TGG TGC GCC GGG CGCG TCT TGG CTT TCT TCT CCT TCG GGC CCT CGG GCC GGT GCT TGT GGGCT CCT CCC GGG CGG CCT CCC CGG GCG GGG GCT TCT TGGCG CTG GCG GGG GGG CCT CCTGCT CTG TGG CTG GGC GTT CCT TGG TGT TCT GGG TGGTGG CGG GCG TGG TGG CCT CTG TGGGGG CCC GCG GCT GCB GGG GTTG CCT GTC TGC TTC 15 GTCCTT TGC GCT CCC GGG CCG CCGGG GTG GGT AGG CCG TGT CTG GGGGTT GGC CAT GTT GGT TGC CGGG CCC GCG GCT GCA GGG G-3' (FRAG. NO:1823) (SEQ. ID NO:1836) 5'-CCC GGG CGG-3' (FRAG. NO:1824) (SEQ. ID NO:1837) 5'-G GCG GGG GGG CC-3' (FRAG. NO:1825) (SEQ. ID NO:1838) 5'-CCC GGG CCG CC-3' (FRAG. NO: 1826) (SEQ. ID NO: 1839) 20 5'-GG CCG TGT-3' (FRAG. NO:1827) (SEQ. ID NO:1840) 5'-GGG GTG GGT BGG CCG TGT CTG GGG-3' (FRAG. NO:1246) (SEQ. ID NO:1255) 5'-GTT GGC CBT GTT GGT TGC C-3' (FRAG. NO:1247) (SEQ. ID NO:1256) 5'-TCT TGG TGG TGC GCC GGG C-3' (FRAG. NO:1248) (SEQ. ID NO:1257) 5'-GCG TCT TGG CTT TCT TCT CCT TCG GGC CCT CGG GCC GGT GCT TGT GG-3'(FRAG.NO:1249)(SEQ.ID 25 NO:1258) 5'-GCT CCT CCC GGG CGG CCT CCC CGG GCG GGG GCT TCT TG-3' (FRAG. NO:1250) (SEQ.ID NO:1259) 5'-GCG CTG GCG GGG GGG CCT CCT CC-3' (FRAG. NO:1251) (SEQ. ID NO:1260) 5'-GCT CTG TGG CTG GGC GTT CCT TGG TGT TCT GGG TGG C-3' (FRAG. NO:1252) (SEQ. ID NO:1261) 5'-TGG CGG GCG TGG TGG CCT CTG TGG TGG-3' (FRAG. NO:1253) (SEQ. ID NO:1262) 30 5'-GGG CCC GCG GCT GCB GGG G-3' (FRAG. NO:1254) (SEQ. ID NO:1263) 5'-TTG CCT GTC TGC TTC GTC-3' (FRAG. NO:1255) (SEQ. ID NO:1264) 5'-CTT TGC GCT CCC GGG CCG CC-3' (FRAG. NO:1256) (SEQ. ID NO:1265) 5'-GGG GTG GGT AGG CCG TGT CTG GGG-3' (FRAG. NO:1257) (SEQ. ID NO:1266) 5'-GTT GGC CAT GTT GGT TGC C-3' (FRAG. NO:1258) (SEQ. ID NO:1267) 35 5'-GGG CCC GCG GCT GCA GGG G-3' (FRAG. NO:1259) (SEQ. ID NO:1268) Human Fibronectin* Antisense Oligonucleotide Fragments 5'-CGG TTT CCT ITG CGG TC TTG GCC CGG GCT CCG GGT G CCC GCC CGC CCG CCG GCC GCC GC CCC GCC GGG CTG TCC CCG CCC CGC CCC GGC CCG GGG CGC GGG GG CGG CCC TCC CGC CCC TCT GG GCC GGC GCG GGC GTC GG CCG CTC GCG CCT GGG GIT CCC TCT CCT CCC CCT GTG C GCC TGC CTC TTG CTC 40 TTCTGC GTC CGC TGC CTT CTC CC CTC TCC TCG GCC GTT GCC TGT GC TGT CCG TCC TGT CGC CCT TCC GTG GTG C TGT TGT CTC TTC TGC CCT C GGT GTG CTG GTG CTG GTG GTG GTG CCT CTG CCC GTG CTC GCCCTG CCT GGG CTG GCC TCT TCG GGT GTG GCT TTG GGG CTC TCT TGG TTG CCC TTT CTT CTC GTG GTG CCT CTC CTC CCT GGC TTG GTC GT TGT CTG GGG TGG TGC TCC TCT CCC TT CCC TGC TGG CCG TTT GT CCT GTT TTC TGT CTT CCT CT TTC CTC CTG TTT CTC CGT TTG GCT TGC TGC TTG CGG GGC TGT 45 CTC C CTT GCC CCT GTG GGC TT CCC TGG TCC GGT CTT CTC CTT GGG GGT C GCC CT CTT GGT GGG CTGGCT CGT CTG TCT TTT TCC TTC C TGG GGG TGG CCG TTG TGG GCG GTG TGG TCC GCC T TGC CTC TGC TGG TCT TTC-3' (FRAG. NO:1828) (SEQ. ID NO: 1841) 5'-GGCCCGGGC-3' (FRAG. NO:1829) (SEQ. ID NO: 1842) 5'-GCCGGCGCGGGCG-3' (FRAG. NO:1830) (SEQ. ID NO:1843) 50 5-GCCTGGGCTGGCC-3' (FRAG. NO:1831) (SEQ. ID NO:'1844) 5'-GGGGG TGGCCG-3' (FRAG. NO:1832) (SEQ. ID NO: 1845) 5'-GG GGG TGG CCG TTG TGG GCG G-3' (FRAG. NO:1833) (SEQ. ID NO: 1846) 5'-CGG TTT CCT TTG CGG TC-3' (FRAG. NO:1260)(SEQ. ID NO:1269) 5'-TTG GCC CGG GCT CCG GGT G-3' (FRAG. NO:1261)(SEQ. ID NO:1270) 55 5'-CCC GCC CGC CCG CCG GCC GCC GC-3' (FRAG. NO:1262)(SEQ. ID NO:1271) 5'-CCC GCC GGG CTG TCC CCG CCC CGC CCC-3' (FRAG. NO:1263)(SEQ. ID NO:1272) 5'-GGC CCG GGG CGC GGG GG-3' (FRAG. NO:1264)(SEQ. ID NO:1273) 5'-CGG CCC TCC CGC CCC TCT GG-3' (FRAG. NO:1265)(SEQ. ID NO:1274) 5'-GCC GGC GCG GGC GTC GG-3' (FRAG. NO:1266)(SEQ. ID NO:1275) 60 5'-CCG CTC GCG CCT GGG GTT CCC TCT CCT CCC CCT GTG C-3' (FRAG. NO:1267)(SEQ. ID NO:1276) 5'-GCC TGC CTC TTG CTC TTC-3' (FRAG. NO:1268)(SEQ. ID NO:1277) 5'-TGC GTC CGC TGC CTT CTC CC-3' (FRAG. NO:1269)(SEQ. ID NO:1278) 5'CTC TCC TCG GCC GTT GCC TGT GC-3' (FRAG. NO:1270)(SEQ. ID NO:1279) 5'-TGT CCG TCC TGT CGC CCT TCC GTG GTG C-3' (FRAG. NO:1271)(SEQ. ID NO:1280) 65 5'-TGT TGT CTC TTC TGC CCT C-3' (FRAG. NO:1272)(SEQ. ID NO:1281) WO 00/62736 PCT/US00/08020 221 5'-GGT GTG CTG GTG CTG GTG GTG GTG-3' (FRAG. NO:1273)(SEQ. ID NO:1282) 5'-CCT CTG CCC GTG CTC GCC-3' (FRAG. NO:1274)(SEQ. ID NO:1283) 5'-CTG CCT GGG CTG GCC TCT TCG GGT-3' (FRAG. NO:1275)(SEQ. ID NO:1284) 5'-GTG GCT TTG GGG CTC TCT TGG TTrG CCC T1T1-3' (FRAG. NO:1276)(SEQ. ID NO:1285) 5 5'-CTT CTC GTG GTG CCT CTC CTC CCT GGC TTG GTC GT-3' (FRAG. NO:1277)(SEQ. ID NO:1286) 5'- TGT CTG GGG TGG TGC TCC TCT CCC-3' (FRAG. NO:1278)(SEQ. ID NO:1287) 5'-TTT CCC TGC TGG CCG TTT GT-3' (FRAG. NO:1279)(SEQ. ID NO:1288) 5'-CCT GTT TTC TGT CTT CCT CT-3' (FRAG. NO:1280)(SEQ. ID NO:1289) 5'-TTC CTC CTG TTT CTC CGT-3' (FRAG. NO:1281)(SEQ. ID NO:1290) 10 5'-TTG GCT TGC TGC TTG CGG GGC TGT CTC C-3' (FRAG. NO:1282)(SEQ. ID NO:1291) 5'-CTT GCC CCT GTG GGC TTT CCC-3' (FRAG. NO:1283)(SEQ. ID NO:1292) 5'-TGG TCC GGT CTT CTC CTT GGG GGT C-3' (FRAG. NO:1284)(SEQ. ID NO:1293) 5'-GCC CTT CTT GGT GGG CTG-3' (FRAG. NO:1285)(SEQ. ID NO:1294) 5'-GCT CGT CTG TCT TTT TCC TTC C-3' (FRAG. NO:1286)(SEQ. ID NO:1295) 15 5'-TGG GGG TGG CCG TTG TGG GCG GTG TGG TCC GCC T-3' (FRAG. NO:1287)(SEQ. ID NO:1296) 5'-TGC CTC TGC TGG TCT TTC-3' (FRAG. NO:1288)(SEQ. ID NO:1297) Human Interleukin-1 (IL-1) Nucleic Acid and antisense Oligocnucleotide Fragments 5'-AAGCT'TCTAC CCTAGTCTGG TGCTACACTT ACATTGCTTA CATCCAAGTG TGGTTATTTC TGTGGCTCCT GTTATAACTA TTATAGCACC AGGTCTATGA CCAGGAGAAT TAGACTGGCA TTAAATCAGA ATAAGAGATT 20 TTrGCACCTGC AATAGACCTT ATGACACCTA ACCAACCCCA TT1ATTACAA TTAAACAGGA ACAGAGGGAA TACTTTATCC AACTCACACA AGCTGTTTTC CTCCCAGATC CATGCTTTTT TGCGTT-TATT ATTTTTAGA GATGGGGGCT TCACTATGTT GCCCACACTG GACTAAAACT CTGGGCCTCA AGTGATTGTC CTGCCTCAGC CTCCTGAATA GCTGGGACTA CAGGGGCATG CCATCACACC TAGTTCATTT CCTCTATTTA AAATATACAT GGCTTAAACT CCAACTGGGA ACCCAAAACA TTCATTTGCT AAGAGTCTGG TGTTCTACCA CCTGAACTAG 25 GCTGGCCACA GGAATTATAA AAGCTGAGAA ATTCTTTAAT AATAGTAACC AGGCAACATC ATTGAAGGCT CATATGTAAA AATCCATGCC TTCCTTTCTC CCAATCTCCA TTCCCAAACT TAGCCACTGG TTCTGGCTGA GGCCTTACGC ATACCTCCCG GGGCTT1GCAC ACACCTTCT7 CTACAGAAGA CACACCTTGG GCATATCCTA CAGAAGACCA GGCTTCTCTC TGGTCCTTGG TAGAGGGCTA CTTTACTGTA ACAGGGCCAG GGTGGAGAGT TCTCTCCTGA AGCTCCATCC CCTCTATAGG AAATGTGTTG ACAATATTCA GAAGAGTAAG AGGATCAAGA 30 CTTCTTTGTG CTCAAATACC ACTGTTCTCT TCTCTACCCT GCCCTAACCA GGAGCTTrGTC ACCCCAAACT CTGAGGTGAT TTATGCCTTA ATCAAGCAAA CTTCCCTCTT CAGAAAAGAT GGCTCATTTT CCCTCAAAAG TTGCCAGGAG CTGCCAAGTA TTCTGCCAAT TCACCCTGGA GCACAATCAA CAAATTCAGC CAGAACACAA CTACAGCTAC TATTAGAACT ATTATTATTA ATAAATTCCT CTCCAAATCT AGCCCCTTGA CTTCGGATTT CACGA'TTCT CCCTTCCTCC TAGAAACTTG ATAAGTTTCC CGCGCTTCCC TTTTITCTAAG ACTACATGTIT 35 TGTCATCTTA TAAAGCAAAG GGGTGAATAA ATGAACCAAA TCAATAACTT CTGGAATATC TGCAAACAAC AATAATATCA GCTATGCCAT CTTTCACTAT TTTAGCCAGT ATCGAGTTGA ATGAACATAG AAAAATACAA AACTGAATTC TTCCCTGTAA ATTCCCCGTT TTGACGACGC ACTTGTAGCC ACGTAGCCAC GCCTACTTAA GACAATTACA AAAGGCGAAG AAGACTGACT CAGGCTTAAG CTGCCAGCCA GAGAGGGAGT CATTTCATTG GCGTTGAGT CAGCAAAGGT ATTGTCCTCA CATCTCTGGC TATTAAAGTA TTTTCTGTTG TTGTTTCT 40 CTTTGGCTGT TTTCTCTCAC ATTGCCTTCT CTAAAGCTAC AGTCTCTCCT TTCTTTTCTT GTCCCTCCCT GGTTTGGTAT GTGACCTAGA ATTACAGTCA GATTTCAGAA AATGATTCTC TCATTTTGCT GATAAGGACT GATTCGTTTT ACTGAGGGAC GGCAGAACTA GTTTCCTATG AGGGCATGGG TGAATACAAC TGAGGCTTCT CATGGGAGGG AATCTCTACT ATCCAAAATT ATTAGGAGAA AATTGAAAAT TTCCAACTCT GTCTCTCTCT TACCTCTGTG TAAGGCAAAT ACCTTATTCT TGTGGTGTTT TT1GTAACCTC T7CAAACTT CATTGATTGA 45 ATGCCTGTTC TGGCAATACA 'TAGGTTGGG CACATAAGGA ATACCAACAT AAATAAAACA TTCTAAAAGA AGTTTACGAT CTAATAAAGG AGACAGGTAC ATAGCAAACT AAT7CAAAGG AGCTAGAAGA TGGAGAAAAT GCTGAATGTG GACTAAGTCA TTCAACAAAG TTTTCAGGAA GCACAAAGAG GAGGGGCTCC CCTCACAGAT ATCTGGATTA GAGGCTGGCT GAGCTGATGG TGGCTGGTGT TCTCTGT7GC AGAAGTCAAG ATGGCCAAAG TTCCAGACAT GTTGAAGAC CTGAAGAACT GTTACAGGTA AGGAATAAGA TTITATCTCTT GTGATTTAAT 50 GAGGGTTTCA AGGCTCACCA GAATCCAGCT AGGCATAACA GTGGCCAGCA TGGGGGCAGG CCGGCAGAGG TTGTAGAGAT GTGTACTAGT CCTGAAGTCA GAGCAGGTTC AGAGAAGACC CAGAAAAACT AAGCATITCAG CATGTTAAAC TGAGATTACA TTGGCAGGGA GACCGCCATT TTAGAAAAAT TATTGAG GTCTGCTGAG CCCTACATGA ATATCAGCAT CAACTTAGAC ACAGCCTCTG TTGAGATCAC ATGCCCTGAT ATAAGAATGG GTTTTACTGG TCCATTCTCA GGAAAACTTG ATCTCATTCA GGAACAGGAA ATGGCTCCAC AGCAAGCTGG 55 GCATGTGAAC TCACATATGC AGGCAAATCT CACTCAGATG TAGAAGAAAG GTAAATGAAC ACAAAGATAA AATTACGGAA CATATTAAAC TAACATGATG TTTCCATTAT CTGTAGTAAA TACTAACACA AACTAGGCTG TCAAAATTTT GCCTGGATAT TTTACTAAGT ATAAATTATG AAATCTGT'IT TAGTGAATAC ATGAAAGTAA TGTGTAACAT ATAATCTATT TGGTTAAAAT AAAAAGGAAG TGCTTCAAAA CCTTTCTTTT CTCTAAAGGA GCTTrAACATT CTTCCCTGAA CTTCAATTAA AGCTCTTCAA TTTGTTAGCC AAGTCCAATT TTTACAGATA 60 AAGCACAGGT AAAGCTCAAA GCCTGTCTTG ATGACTACTA AITCCAGATT AGTAAGATAT GAATTACTCT ACCTATGTGT ATGTGTAGAA GTCCTTAAAT TTCAAAGATG ACAGTAATGG CCATGTGTAT GTGTGTGACC CACAACTATC ATGGTCATTA AAGTACATTG GCCAGAGACC ACATGAAATA ACAACAATTA CATTCTCATC ATCTATTTT GACAGTGAAA ATGAAGAAGA CAGTTCCTCC ATTGATCATC TGTCTCTGAA TCAGGTAAGC AAATGACTGT AAT7CTCATG GGACTGCTAT TCTTACACAG TGGTTTCTTC ATCCAAAGAG AACAGCAATG 65 ACTTGAATCT TAAATACTTT TGTTTACCC TCACTAGAGA TCCAGAGACC TGTCTTTCAT TATAAGTGAG WO 00/62736 PCT/US00/08020 222 ACCAGCTGCC TCTCTAAACT AATAGTTGAT GTGCATTGGC T7CTCCCAGA ACAGAGCAGA ACTATCCCAA ATCCCTGAGA ACTGGAGTCT CCTGGGGCAG GCTTCATCAG GATGTrAGTT ATGCCATCCT GAGAAAGCCC CGCAGGCCGC TTCACCAGGT GTCTGTCTCC TAACGTGATG TGTrGTGGTT GTCTTCTCTG ACACCAGGAT CAGAGGTrAG AGAAAGTCTC CAAACATGAA GCTGAGAGAG AGGAAGCAAG CCAGCTGAAA GTGAGAAGTC 5 TACAGCCACT CATCAATCTG TGTrA TTGTG TITGGAGACC ACAAATAGAC ACTATAAGTA CTGCCTAGTA TGTCT'rCAGT ACTGGC1TTTA AAAGCTGTCC CCAAAGGAGT ATrTCTAAAA TATITTGAGC ArTT~AAGC AGAT11TAA CCTCCTGAGA GGGAACTAAT TGGAAAGCTA CCACTCACTA CAATCA FTGT TAACCTATrT AGTI'ACAACA TCTCATTT GAGCATGCAA ATAAATGAAA AAGTCTTCCT AAAAAAATCA TCTVrrATC CTGGAAGGAG GAAGGAAGGT GAGACAAAAG GGAGAGAGGG AGGGAAGCCT AATGAAACAC CAG FTACCTA 10 AGACCAGAAT GGAGATCCTC CTCACTACCT CTGTrGAATA CAGCACCTAC TGAAAGAACT TTCATTCCCT GACCATGAAC AGCCTCTCAG CTrCTGT=T C=TCCTCAC AGAAATCCTT CTATCATGTA AGCTATGGCC CACTCCATGA AGGCTGCATG GATCAATCTG TGTCTCTGAG TATCTCTGAA ACCTCTAAAA CATCCAAGCT TACCTCAAG GAGAGCATGG TGGTAGTAGC AACCAACGGG AAGGTCTGA AGAAGAGACG GTTGAGTTTA AGCCAATCCA TCACTGATGA TGACCTGGAG GCCATCGCCA ATGACTCAGA GGAAGGTAAG GGGTCAAGCA 15 CAATAATATC T1TTC'T11AC AGT'ITTAAGC AAGTAGGGAC AGTAGAAYI17 AGGGGAAAAT TAAACGTGGA GTCAGAATAA CAAGAAGACA ACCAAGCATT AGTCTGGTAA CTATACAGAG GAAAATTAAT TTITATCCTT CTCCAGGAGG GAGAAATGAG CAGTGGCCTG AATCGAGAAT ACTTGCTCAC AGCCA'rrATT TCTTAGCCAT ATTGTAAAGG TCGTGTGACT TITAGCC'Tr CAGGAGAAAG CAGTAATAAG ACCACTFACG AGCTATGTTC CTGTCATACT AACTATGCCT CCITFGGTCAT GTTACATAAT C'II1CGTGA TTCAGMhCC TCTACTGTAA 20 AATGGAGATA ATCAGAATCC CCCACTCATT GGATFTG FGT AAAGATTAAG AGTCTCAGGC TTTACAGACT GAGCTAGCTG GGCCCTCCTG ACTGTTATAA AGAY~rAAATG AGTCAACATC CCCTAAC'rC TGGACTAGAA TAATGTCTGG TACAAAGTAA GCACCCAATA AATGTTAGCT A'ITACTATCA TTATTATTAT TATTI'TA1TT 'r'rr=G AGATGGAGTC TGGCTCTGTC ACCCAGGCTG GAGTGCAGTG GCACAATCTC GGCTCACTGC AAGCTCTGCC TCCTGGGTTC ATGCCATTCT CCTGCCTCAG CCTCCCGAGT AAGCTGGGAA TACAGGCACC 25 CGCCACTGTI' CCCGGCTAAT 'TITIGTATT TITAGTAGAG ACGGAGTrTC ACCGTGGTCT CCATCTCCTC GTGATCCACC CACC'ITGGCC TCCCAAAGTG CCGGGATTAC AGGCGTGAGC CACCGCGCCC GGCCTATTAT TATTATTATr ACTACTACTA CTACCTATAT GAATACTACC AGCAATACTA A TATAAT GACTGGATTA TGTCTAAACC TCACAAGAAT CCTACCTTCT CAl=iACAT AAAAGGAAAC TAAGCTCATI' GAGATAGGTA AACTGCCCAA TGGCATACAT CTGTAAGTGG GAGAGCCTCA AATCTAATrC AGTT1CTACCT GAGTAAAAAA 30 ATCATGG=1 CTCCTCCATC CC'1ACTGT ACAAGCCTCC ACATGAACTA TAAACCCAAT ArrCCTGTrT TTAAGATAAT ACCTAAGCAA TAACGCATGT TCACCTAGAA GGTITAAAA TGTAACAAAA TATAAGAAAA TAAAAATCAC TCATATCGTC AGTGAGAGTT TACTACTGCC AGCACTATGG TATGTI17CCT TAAAATCTrT GCTATACACA TACCTACATG TGAACAAATA TGTCTAACAT CAAGACCACA CTAYI17ACAA CTTATATCC AGCtTMCF ACTTAGCAAT GTATTGAGGA CATITAGAG TGCCCGTIT TCACCATTAT AAGCAATGCA 35 ACAATGAACA TCTGTATAAA TAAATATTCA TITCTCTCAC CCTITATTTC CTTAGAATAT ATTCCTAGAA GTAGAAT'ITC CCAGAGCCAT GAGGA ITGT GACGCTATTG ATATGTGCCA CT1'GCACTC TCTGTGACAT ATATAATI'AT =1IAATGCA TTCATTT TCTCAGAGTG CA'ITCGTTTG AAAACATAGA CGGGAAATAC TGGTAGTCTT CCTTGTCAGT TAGAAACACC CAAACAATGA AAAATGAAAA AGTTGCACAA ATAGTCTCTA AAAACAATGA AACTATTGCC TGAGGAATTG AAG'1TTAAAA AGAAGCACAT AAGCAACAAC AAGGATAATC 40 CTAGAAAACC AGTTCTGCTG ACTGGGTGAT 'rTCACT-TCTC MIGC3TCCT CATCTGGATI' GGAATATrCC TAATACCCCC TCCAGAACTA TITCCCTGT TTGTACTAGA CTGTGTATAT CATCTGTGTT TGTACATAGA CATTAATCTG CAC'I7GTGAT CATGGTMTA GAAATCATCA AGCCTAGGTC ATCACCTIT AGCTTCCTGA GCAATGTGAA ATACAAC'= ATGAGGATCA TCAAATACGA AT-rCATCCTG AATGACGCCC TCAATCAAAG TATAAYI7CGA GCCAATGATC AGTACCTCAC GGCTGCTGCA TTACATAATC TGGATGAAGC AGGTACATTA 45 AAATGGCACC AGACAITTTCT GTCATCCTCC CCTCC'TCA TTrACTTA'IT TATTTAT1TC AATCTTTCTG CTTGCAAAAA ACATACCTCT TCAGAGTI'CT GGG'ITGCACA AYTCTTCCAG AATAGC'FrGA AGCACAGCAC CCCCATAAAA ATCCCAAGCC AGGGCAGAAG GTTCAACTAA ATCTGGAAGT TCCACAAGAG AGAAG'TTCC TATCTITGAG AGTAAAGGGT TGTGCACAAA GCTAGCTGAT GTACTACCTC TrTGGrrTr TCAGACATTC TTACCCTCAA TITTAAAACT GAGGAAACTG TCAGACATAT TAAATGATI17 ACTCAGAMII ACCCAGAAGC 50 CAATGAAGAA CAATCACTCT CCTIT7AAAAA GTCTGTI'GAT CAAACTCACA AGTAACACCA AACCAGGAAG ATC TTATTA TCTCTGATAA CATA'ITTGTG AGGCAAAACC TCCAATAAGC TACAAATATG GCTITAAAGGA TGAAGTIAG TGTCCAAAAA C'IIATCAC ACACATCCAA TITCATGGC GGACATGMf TAGTTTCAAC AGTATACATA TIICAAAGG TCCAGAGAGG CAAT=GCA ATAAACAAGC AAGACTITI CTGATTGGAT GCACTTCAGC TAACATGCTT TCAACTCTAC ATACAAAT TATITGTGT TCTATTTC TACTTAATAT 55 TATI'TCTGCA ATITCCCAA TA'ITGACATC GTGTATGTAT TTGCCA'II TAATATCACT AGACAAT7CA ATCAGG ITGC TACGTTGGTC CCTrGGGTIT ACTCTAAATA GC TGATTGC AAATATCMV GTATATATTA TrGT1T1TC TCCTATCTTG TAMTTC'TT GAGCACATCC CAAAGAGGAA TGCCTAGATC AATGGGCACA AATAATITGA CAGCTCTrAT TAAACATTAT TCTGTAAGTA AAAACTGAAC TACTITT7CAG TATCACTAGC AACATATGAG TGTATCAGCT TCCTAAACCC CTCCATGTTA GGTCATTATG AACTTATGAT CTAACAAATr 60 ACAGGGTC'1T ATCCCACTAA TGAAATTATA AGAGATTCAA CACTTAFCA GCCCCGAAGG ATTCATTCAA CGTAGAAAAT TCTAAGAACA TTAACCAAGT ATTTACCTGC CTAGTGAGTG TGGAAGACAT TGTGAAGGAC ACAAAGATGT ATAGAATTCC ATCCTGACT TCCAGGTAT TACACCATAG GTGGGGACCT AACTACACAC ACACACACAC ACACACACAC ACACACACAC ACCATGCACA CACAATCTAC ATCAACACTT GATITATAC AAATACAATG AATITAC'TI' C'TTrGGTT CTTCTCTTCA CCAGTGAAAT TTGACATGGG TGCTrATAAG 65 TCATCAAAGG ATGATGCTAA AA'TrACCGTG AITCTAAGAA TCTCAAAAAC TCAATTGTAT GTGACTGCCC AAGATGAAGA CCAACCAGTG CTGCTGAAGG TCAGTI7GTCC 'TrGTCTCCA ACTTACCTTC ATI1ACATCT WO 00/62736 PCT/USOO/08020 223 CATATGTTTG TAAATAAGCC CAATAGGCAG ACACCTCTAA CAAGGTGACA CTGTCCTCTT TCCTTCCTAC CACAGCCCCC ACCTACCCAC CCCACTCCCA TTGATTCCAG AGGCGTGCCT AGGCAGGATC TATGAGAAAA TATAACAGAG AGTAAGAGGA AAATTACCTT CTTTCTTTTT CCTTCCCTG CCTGACCTTA TTCACCTCCC ATCCCAGAGC ATCCATTTAT TCCATTGATC TTTACTGACA TCTATTATCT GACCTACACA ATACTAGACA 5 TTAGGACAAT GTGGCCTGCC TCCAAGAAAC TCAAATAAGC CAACTGAGAT CAGAGAGGAT TAATCACCTG CCAATGGGCA CAAAGCAACA AGCTGGGAGC CAAGTCCCAA AATGGGGCCT GCTGCTTCCA GTTCCCCTCT CTCTGCATTG ATGTCAGCAT TATCCTTCGT CCCAGTCCTG TCTCCACTAC CACTTTCCCC CTCAAACACA CACACACACA ACAGCCTTAG ATGTTTTCTC CACTGATAAG TAGGTGACTC AATTTGTAAG TATATAATCC AAGACCTTCT ATTCCCAAGT AGAATTTATG TGCCTGCCTG TGCTTTTCTA CCTGGATCAA GTGATGTCTA 10 CAGAGTAGGG CAGTAGCTTC ATTCATGAAC TCATTCAACA AGCATTATTC ACTGAGAGCC TTGTATTTT CAGGCATAGT GCCAACAGCA GTGTGGACAG TGGTGCATCA AAGCCTCTAG TCTCATAGAA CTTAGTCTTC TGGAGGATAT GGAAAACAGA CAACCCAAAC AACCAACAAA AGAGCAAGAT GCTGCAAAAA AAAAAAAAAT GAATAGGGTG CTAAGATAGA GAAAAGTGGG AGAGTGCTAT TTAGACAAAG TGGTAAAAAC AAAGCCCCTT GTGAGATGAG AGCTGCCGAC AGAGGGGGCG GGTCATGGTT GTGGGTTTTT GGGTAGGACA TTCAGAGGAG 15 GGGGCGGGTC GTGGTTGTGG GTTTGGGT AGGACATTCA GAGGAGGGGG CGGGTCGTGG TTGTGGGTTT TTGGGTAGGA CATTCAGAGG AGGGGGCGGG TCGTGGTTGT GGGTTTGG GTAGGACATT CAGAGGAGGG GGCGGGTCGT GGTTGTGGGT TTTTGGGACA TTCAGAGGAG TCTGAATGCA CCCAGGCCTA CAACTTCAAG ATGGTAAAGG ACAGCTCCAA GGATCAGAAG AAGCATTCTT GGAACTGGGG CATTTTGAGA AGGAGGAAAA ATATGCAGAG ACTAGTGCTT GCAGAGCTTG CATTTGGATT TCATTTGAGG TACAATGAAA ACCCATTAAT 20 GGGTTTCACA CAGTGCAATG GCCTGACCTC ACTTATATTT CCTAAAATAG AAAACAGATC AGAAGGAAGG CAATAGAGAA GCAGAAAGTC CAATGAGGAG GTTTCACAGC AGTCATGGGG GTGGGGTAAG GAAAAGAAGT GGAAAGAAAC AGACAGAATT GGGTTATATT TTGGAGATAG AACCAACAGA AGGAAGAGGA GAAACAACAT TTACTGAGAA GGGAAAAAGT AGGAGAGGAA TAGGTTTGGG AAATAAATCC TGCTGACATT GGAAACCCCA AGGAAGCCTC AAAAGTATAT TTACTTGCTT TAGATTAAA AGAATAGGAA AGAAGCATCT CAACTTGGAA 25 TTTGAAATCT ATTTTTCCAT AAAAGTATTG TTAAATTCTA CTCATACTCA CAAGAAAAGT ACATTCTAAA GAGTATATTG AAAGAGTTTA CTGATATACT TAGGAATTTT GTGTGTATGT GTGTGTGTGT ATGTGTGTGT GTGTGTTTAA CCTTCAATTG TTGACTTAAA TACTGAGATA AATGTCATCT AAATGCTAAA TTGATTTCCC AAAGGTATGA TTTGTTCACT TGGAGATCAA AATGTTTAGG GGGCTTAGAA TCACTGTAGT GCTCAGATTT GATGCAAAAT GTCTTAGGCC TATGTTGAAG GCAGGACAGA AACAATGTTT CCCTCCTACC TGCCTGGATA 30 CAGTAAGATA CTAGTGTCAC TGACAATCTT CATAACTAAT TTAGATCTCT CTCCAATCAA CTAAGGAAAT CAACTCTTAT TAATAGACTG GGCCACACAT CTACTAGGCA TGTAATAAAT GCTTGCTGAA TGAACAAATG AATGAAGAGC CTATAGCATC ATGTTACAGC CATAGTCCTA AAGTGGTGTT TCTCATGAAG GCCAAATGCT AAGGGATTGA GCTTCAGTCC TTCTAAC ATCTTGTTCT CTAACAGAAT TCTCTTCTTT TCTTCATAGG AGATGCCTGA GATACCCAAA ACCATCACAG GTAGTGAGAC CAACCTCCTC TTCTTCTGGG AAACTCACGG 35 CACTAAGAAC TATTTCACAT CAGTTGCCCA TCCAAACTTG TTTATTGCCA CAAAGCAAGA CTACTGGGTG TGCTTGGCAG GGGGGCCACC CTCTATCACT GACTTTCAGA TACTGGAAAA CCAGGCGTAG GTCTGGAGTC TCACTTGTCT CACTTGTGCA GTGTTGACAG TTCATATGTA CCATGTACAT GAAGAAGCTA AATCCTTTAC TGTTAGTCAT TTGCTGAGCA TGTACTGAGC CTTGTAATTC TAAATGAATG TTTACACTCT TTGTAAGAGT GGAACCAACA CTAACATATA ATGTTGTTAT TTAAAGAACA CCCTATATTT TGCATAGTAC CAATCATTTT 40 AATTATTATT CTTCATAACA ATTTTAGGAG GACCAGAGCT ACTGACTATG GCTACCAAAA AGACTCTACC CATATTACAG ATGGGCAAAT TAAGGCATAA GAAAACTAAG AAATATGCAC AATAGCAGTT GAAACAAGAA GCCACAGACC TAGGATTTCA TGATTTCATT TCAACTGTTT GCCTTCTGCT TTTAAGTTGC TGATGAACTC TTAATCAAAT AGCATAAGTT TCTGGGACCT CAGTTTTATC ATTTTCAAAA TGGAGGGAAT AATACCTAAG CCTTCCTGCC GCAACAGTTT TTTATGCTAA TCAGGGAGGT CATTTTGGTA AAATACTTCT CGAAGCCGAG 45 CCTCAAGATG AAGGCAAAGC ACGAAATGTT ATTTTTTAAT TATTATTTAT ATATGTATTT ATAAATATAT TTAAGATAAT TATAATATAC TATATTTATG GGAACCCCTT CATCCTCTGA GTGTGACCAG GCATCCTCCA CAATAGCAGA CAGTGTTTTC TGGGATAAGT AAGTTTGATT TCATTAATAC AGGGCATTTT GGTCCAAGTT GTGCTTATCC CATAGCCAGG AAACTCTGCA TTCTAGTACT TGGGAGACCT GTAATCATAT AATAAATGTA CATTAATTAC CTTGAGCCAG TAATTGGTCC GATCTTTGAC TCTTTTGCCA TTAAACTTAC CTGGGCATTC 50 TTGTTTCATT CAATTCCACC TGCAATCAAG TCCTACAAGC TAAAATTAGA TGAACTCAAC TTTGACAACC ATGAGACCAC TGTTATCAAA ACTTTCTTTT CTGGAATGTA ATCAATGTTT CTTCTAGGTT CTAAAAATTG TGATCAGACC ATAATGTTAC ATTATTATCA ACAATAGTGA TTGATAGAGT GTTATCAGTC ATAACTAAAT AAAGCTTGCA ACAAAATTCT CTGACACATA GTTATTCATT GCCTTAATCA TTATTTTACT GCATGGTAAT TAGGGACAAA TGGTAAATGT TTACATAAAT AATrGTATTT AGTGTTACTT TATAAAATCA AACCAAGATT 55 TTATATTTTT TTCTCCTCTT TGTTAGCTGC CAGTATGCAT AAATGGCATT AAGAATGATA ATATTTCCGG GTTCACTTAA AGCTCATATT ACACATACAC AAAACATGTG TTCCCATCTT TATACAAACT CACACATACA GAGCTACATT AAAAACAACT AATAGGCCAG GCACGGTGGC TCAGACCTGT AATCCCAGCA CTTTGGGAGG ACCAACCTCT TCGAGGCACA AGGCACAACA GGCTGCTCTG GGATTCTCTT CAGCCAATCT TCATTGCTCA AGTGTCTGAA GCAGCCATGG CAGAAGTACC TGAGCTCGCC AGTGAAATGA TGGCTTATTA CAGTGGCAAT 60 GAGGATGACT TGTTCTTTGA AGCTGATGGC CCTAAACAGA TGAAGTGCTC CTTCCAGGAC CTGGACCTCT GCCCTCTGGA TGGCGGCATC CAGCTACGAA TCTCCGACCA CCACTACAGC AAGGGCTTCA GGCAGGCCGC GTCAGTTGTT GTGGCCATGG ACAAGCTGAG GAAGATGCTG GTTCCCTGCC CACAGACCTT CCAGGAGAAT GACCTGAGCA CCTTCTTTCC CTTCATCTTT GAAGAAGAAC CTATCTTCTT CGACACATGG GATAACGAGG CTTATGTGCA CGATGCACCT GTACGATCAC TGAACTGCAC GCTCCGGGAC TCACAGCAAA AAAGCTTGGT 65 GATGTCTGGT CCATATGAAC TGAAAGCTCT CCACCTCCAG GGACAGGATA TGGAGCAACA AGTGGTGTTC TCCATGTCCT TTGTACAAGG AGAAGAAAGT AATGACAAAA TACCTGTGGC CTTGGGCCTC AAGGAAAAGA WO 00/62736 PCT/USOO/08020 224 ATCTGTACCT GTCCTGCGTG TTGAAAGATG ATAAGCCCAC TCTACAGCTG GAGAGTGTAG ATCCCAAAAA 'ITACCCAAAG AAGAAGATGG AAAAGCGATT TGTC'TrCAAC AAGATAGAAA TCAATAACAA GCTGGAA'1T GAGTCTGCCC AGTFCCCCAA CTGGTACATC AGCACCTCTC AAGCAGAAAA CATGCCCGTC TTCCTGGGAG GGACCAAAGG CGGCCAGGAT ATAACTGACT TCACCATGCA A'I~rGTGTCT TCCTAAAGAG AGCTGTACCC 5 AGAGAGTCCT GTGCTGAATG TGGACTCAAT CCCTAGGGCT GGCAGAAAGG GAACAGAAAG GTITL1GAGT ACGGCTATAG CCTGGACTTT CCTGTrGTCT ACACCAATGC CCAACTGCCT GCCTrAGGGT AGTGCTAAGA GGATCTCCTG TCCATCAGCC AGGACAGTCA GCTCTCTCCT TrCAGGGCCA ATCCCCAGCC CTITT~GA GCCAGGCCTC TCTCACCTCT CCTACTCACT TAAAGCCCGC CTGACAGAAA CCACGGCCAC A = GGTTCT AAGAAACCCT CTGTCATTCG CTCCCACATT CTGATGAGCA ACCGCTTCCC TAMT TTA ThrAT-rrGTr 10 TGTTGTTI ATFCATTGGT CTAATITATl CAAAGGGGGC AAGAAGTAGC AGTGTCTGTA AAAGAGCCTA GTTAATA GCTATGGAAT CAATTCAATT TGGACTGGTG TGCTCTCTT AAATCAAGTC C'ITTAATTAA GACTGAAAAT ATATAAGCTC AGATTA'TTA AATGGGAATA TI1ATAAATG AGCAAATATC ATACTGTrCA ATGGTTCTGA AATAAACTTC TCTGAAG AGAAAGAAAG AGAGAGAGAA AGAAAAGAAA GAGGAAGGAA GGAAGGAAGG AAGAAAGACA GGCTCTGAGG AAGGTGGCAG 17CCTACAAC GGGAGAACCA GTGG'rrAATr 15 TGCAAAGTGG ATCCTGTGGA GGCANNCAGA GGAGTCCCCT AGGCCACCCA GACAGGGCTT TTAGCTATCT GCAGGCCAGA CACCAAATH' CAGGAGGGCT CAGTGTI7AGG AATGGATTAT GGCTTATCAA ATTCACAGGA AACTAACATG TTGAACAGCT TrTAGATTTC CTGTGGAAAA TATAACTTAC TAAAGATGGA GTTCT7GTGA CTGACTCCTG ATATCAAGAT ACTGGGAGCC AAATFAAAAA TCAGAAGGCT GCTTGGAGAG CAAGTCCATG AAATGCTCTT TITCCCACAG TAGAACCTAT ITCCCTCGTG TCTCAAATAC TTGCACAGAG GCTCACTCCC 20 17GGATAATG CAGAGCGAGC ACGATACCTG GCACATACTA A'ITTGAATAA AATGCTGTCA AATTCCCATT CACCCAT7CA AGCAGCAAAC TCTATCTCAC CTGAATGTAC ATGCCAGGCA CTGTGCTAGA CTTGGCTCAA AAAGATTTCA GTI17CCTGGA GGAACCAGGA GGGCAAGGTT TCAACTCAGT GCTATAAGAA GTGTrrACAGG CTGGACACGG TGGCTCACGC CTGTAATCCC AACA'IMGGG AGGCCGAGGC GGGCAGATCA CAAGGTCAGG AGATCGAGAC CATCCTGGCT AACATGGTGA AACCCTGTCT CTACTAAAAA TACAAAAAAT TAGCCGGGCG 25 T7GGCGGCAG GTGCCTGTAG TCCCAGCTGC TGGGGAGGCT GAGGCAGGAG AATGGTGTGA ACCCGGGAGG CGGAACTTGC AGGGGGCCGA GATCGTGCCA CTGCACTCCA GCCTGGGCGA CAGAGTGAGA CTCTGTCTCA AAAAAAAAAA AAAAGTGTTA TGATGCAGAC CTGTCAAAGA GGCAAAGGAG GGTGTI'CCTA CACTCCAGGC ACTGTTCATA ACCTGGACTC TCATTCATTC TACAAATGGA GGGCTCCCCT GGGCAGATCC CTGGAGCAGG CAC'I]GCTG GTGTCTCGGT TAAAGAGAAA CTGATAACTC T7GGTATrAC CAAGAGATAG AGTCTCAGAT 30 GGATATFCTT ACAGAAACAA TATTCCCACT T-ITCAGAGTr CACCAAAAAA TCATJTAGG CAGAGCTCAT CTGGCATTGA TCTGGTrCAT CCATGAGAT7 GGCTAGGGTA ACAGCACCTG GTCT-FGCAGG GT7GTGTGAG CTTATCTCCA GGGTTGCCCC AACTCCGTCA GGAGCCTGAA CCCTGCATAC CGTATGTTrCT CTGCCCCAGC CAAGAAAGGT CAAYTrTCTC CTCAGAGGCT CCTGCAAT11G ACAGAGAGCT CCCGAGGCAG AGAACAGCAC CCAAGGTAGA GACCCACACC CTCAATACAG ACAGGGAGGG CTATTGGCCC TTCA'ITGTAC CCA'ITTATCC 35 ATCTGTAAGT GGGAAGATTC CTAAACTTAA GTACAAAGAA GTGAATGAAG AAAAGTATGT GCATGTATAA ATCTGTGTGT CTTCCACITTF GTCCCACATA TACTAAATrT AAACAYrCTT CTAACGTGGG AAAATCCAGT ATITAATGT GGACATCAAC TGCACAACGA TI'GTCAGGAA AACAATGCAT A ITTGCATGG TGATACATT GCAAAATGTG TCATAG ITTG CTACTCCTTrG CCCrFCCATG AACCAGAGAA TTATCTCAGT TTATTAGTCC CCTCCCCTAA GAAGCTTCCA CCAATACTCT TrCCCC'= CC'ITTAACTr GAT7GTGAAA TCAGGTATC 40 AACAGAGAAA TI1'CTCAGCC TCCTACTTCT GC'1TGAAA GCTATAAAAA CAGCGAGGGA GAAACTGGCA GATACCAAAC CTCT7CGAGG CACAAGGCAC AACAGGCTGC TCTGGGATrC TCTTCAGCCA ATCTTCATTG CTCAAGTATG AC'TrTAATCT TCCTTACAAC TAGGTGCTAA GGGAGTCTCT CTGTCTCTCT GCCTCTTTGT GTGTATGCAT ATTCTCTCTC TCTCTCTCTT TCT=CTCTG TCTCTCCTCT CCTTCCTCTC TGCCTCCTCT CTCAGCTT TGCAAAAATG CCAGGTGTAA TATAATGCTI' ATGACTCGGG AAATATTCTG GGAATGGATA 45 CTGCTI1ATCT AACAGCTGAC ACCCTAAAGG TTAGTGTCAA AGCCTCTGCT CCAGCTCTCC TAGCCAATAC ATTGCTAG'JT GGGGTGGT TTAGCAAATG C=ICTCTA GACCCAAAGG ACTTCTC'LM CACACATI'CA TT1CA=IIACT CAGAGATCAT TTC'rfrGCAT GACTGCCATG CACTGGATGC TGAGAGAAAT CACACATGAA CGTAGCCGTC ATGGGGAAGT CACTCAT1T CTCCTITA CACAGGTGTC TGAAGCAGCC ATGGCAGAAG TACCTGAGCT CGCCAGTGAA ATGATGGCTT ATTACAGGTC AGTGGAGACG CTGAGACCAG TAACATGAGC 50 AGGTCTCCTC TffCAAGAGT AGAGTGTTAT CTGTGCTTGG AGACCAGATT ITCCCCTAA ATTGCCTCTT TCAGTGGCAA ACAGGGTGCC AAGTAAATCT GATAAAGA CTACTrCCC A11?ACAAGTC CCTCCAGCCT TGGGACCTGG AGGCTATCCA GATGTGTTGT TGCAAGGGCT TCCTGCAGAG GCAAATGGGG AGAAAAGATr CCAAGCCCAC AATACAAGGA ATCCCTTGC AAAGTGTGGC TTGGAGGGAG AGGGAGAGCT CAGATITAG CTGACTCTGC TGGGCTAGAG GTTAGGCCTC AAGATCCAAC AGGGAGCACC AGGGTGCCCA CCTGCCAGGC 55 CTAGAATCTG CCTTCTGGAC TG'ITCTGCGC ATATCACTGT GAAACTTGCC AGGTGTTTCA GGCAGCTI17G AGAGGCAGGC TG'1TTGCAGT 'ITC'ITATGAA CAGTCAAGTC TTGTACACAG GGAAGGAAAA ATAAACCTGT TTAGAAGACA TAATTGAGAC ATGTCCCTGT =A1r IACA GTGGCAATGA GGATGACTTG TTCT117GAAG CTGATGGCCC TAAACAGATG AAGGTAAGAC TATGGGTITA ACTCCCAACC CAAGGAAGGG CTCTAACACA GGGAAAGCTC AAAGAAGGGA GTITCTGGGCC ACTITGATGC CATGGTATr7 TGTfI1'AGAA AGACTrTAAC 60 CTCTTCCAGT GAGACACAGG CTGCACCACT TGCTGACCTG GCCACTrGGT CATCATATCA CCACAGTCAC TCACTAACGT TGGTGGTGGT GGCCACACTr GGTGGTGACA GGGGAGGAGT AGTGATAATG TTCCCAMTC ATAGTAGGAA GACAACCAAG TCYI'CAACAT AAATT7GATT ATCC~fTTAA GAGATGGATr CAGCCTATGC CAATCACT'TG AGTTAAACTC TGAAACCAAG AGATGATCTT GAGAACTAAC ATATGTCTAC CCCTTITGAG TAGAATAGTT TIMGCTACC TGGGGTGAAG CT7ATAACAA CAAGACATAG ATGATATAAA CAAAAAGATG 65 AATTGAGACT TGAAAGAAAA CCATrCACTT GCTGTrrGAC CrGACAAGT CATTACCC GC'ITTGGACC TCATCTGAAA AATAAAGGGC TGAGCTGGAT GATCTCTGAG ATI'CCAGCAT CCTGCAACCT CCAGTI7CTGA WO 00/62736 PCT/USOO/08020 225 AATMTTCA GTI'GTAGCTA AGGGCATTTG GGCAGCAAAT GGTCATfTr CAGACTCATC CTrACAAAGA GCCATGTrrAT ATCCTGCTG TCCCTTCTGT TTATATGAT GCTCAGTAGC CTTCCTAGGT GCCCAGCCAT CAGCCTAGCT AGGTCAG'I1G TGCAGGTTGG AGGCAGCCAC TITCTCTGG CTTTATflTTA TrCCAGTrTG TGATAGCCTC CCCTAGCCTC ATAATCCAGT CCTCAATCTI' GTTAAAAACA TATrCTTTA GAAGTITAA 5 GACTGGCATA ACTI7CTT1GGC TGCAGCTGTG GGAGGAGCCC ATT1GGCTTGT CTGCCTGGCC TTITGCCCCCC ATfTGCCT=T CCAGCAGC'T GGCTCTGCTC CAGGCAGGAA ATTCTCTCCT GCTCAAC'ITr CT1TTGTGCA CTTACAGGTC TC'I11AACTG TCTTTCAAGC CTTTGAACCA 'ITATCAGCCT TAAGGCAACC TCAGTGAAGC C'JTAATACGG AGCTI'CTCTG AATAAGAGGA AAGTGGTAAC ATTTCACAAA AAGTACTCTC ACAGGATTTG CAGAATGCCT ATGAGACAGT GTTATGAAAA AGGAAAAAAA AGAACAGTGT AGAAAAATTG AATACTTGCT 10 GAGTGAGCAT AGGTGAATGG AAAATGTTAT GGTCATCTGC ATGAAAAAGC AAATCATAGT GTGACAGCAT TAGGGATACA AAAAGATATA GAGAAGGTAT ACATGTATGG TGTAGGTGGG GCATGTACAA AAAGATGACA AGTAGAATCG GGAT= ATI'C TAAAGAATAG CCTGTAAGGT GTCCAGAAGC CACATI'CTAG TCYTGAGTCT GCCTCTACCT GCTGTGTGCC CTTGAGTACA CCCTTAACCT CCTTGAGC'IT CAGAGAGGGA TAATCTrT ATTA A TPTA'ITI GTITIGITT GTI=G1TI G'T='ATGAG ACAGAGTCTC ACTCTGTrGC 15 CCAGGCTGGA GTGCAGTGGT ACAATCTTGG CTITACTGCAT CCTCCACCTC CTGAGTTCAA GCGATTCTCC TTCCTCAGTC TCCTGAATAG CTAGGATTAC AGGTGCACCC CACCACACCC AGCTAA=Ir TGTATTrA GTAGAGAAGG GGTI1TCGCCA TGTTGGCCAG GCTGGT=TG AAGTCCTGAC CTAAATGATT CATCCACCTC GGCTTCCCAA AGTGCTGGGA TITACAGGCAT GAGCCACCAC GCCTGGCCCA GAGAGGGATG ATC'frTAGAA GCTCGGGA'IT CTTTCAAGCC CTI17CCTCCT CTCTGAGCIT TCTACTCTCT GATGTCAAAG CATGGTTCCT 20 GGCAGGACCA CCTCACCAGG CTCCCTCCCT CGCTCTCTCC GCAGTGCTCC TTCCAGGACC TGGACCTCTG CCCTCTGGAT GGCGGCATCC AGCTACGAAT CTCCGACCAC CACTACAGCA AGGGCTTCAG GCAGGCCGCG TCAGTrG317G TGGCCATGGA CAAGCTGAGG AAGATGCTGG TTCCCTGCCC ACAGACCTTC CAGGAGAATG ACCTGAGCAC CTrC'ITrCCC TTCATCTI-G AAGAAGGTAG TTAGCCAAGA GCAGGCAGTA GATCTCCACT TGTGTCCTCT TGGAAGTCAT CAAGCCCCAG CCAACTCAAT TCCCCCAGAG CCAAAGCCCT TI'AAAGGTAG 25 AAGGCCCAGC GGGGAGACAA AACAAAGAAG GCTGGAAACC AAAGCAATCA TCTCTTTAGT GGAAACTAITF CTTAAAGAAG ATCTTGATGG CTACTGACAT TI'GCAACTCC CTCACTCTrT CTCAGGGGCC 1TTCACTYFAC ATTGTCACCA GAGGTTCGTA ACCTCCCTGT GGGCTAGTGT TATGACCATC ACCATI=AC CTAAGTAGCT CTGTTGCTCG GCCACAGTGA GCAGTAATAG ACCTGAAGCT GGAACCCATG TCTAATAGTG TCAGGTCCAG TGTTCTTAGC CACCCCACTC CCAGCTrCAT CCCTACTGGT GTTGTCATCA GACTTTGACC GTATATGCTC 30 AGGTGTCCTC CAAGAAATCA AAYITGCCA CCTCGCCTCA CGAGGCCTGC CCT-rCTGATT YTATACCTAA ACAACATGTG CTCCACATTT CAGAACCTAT CTTCTTCGAC ACATGGGATA ACGAGGCTTA TGTGCACGAT GCACCTGTAC GATCACTGAA CTGCACGCTC CGGGACTCAC AGCAAAAAAG CTTGGTGATG TCTGGTCCAT ATGAACTGAA AGCTCTCCAC CTCCAGGGAC AGGATATGGA GCAACAAGGT AAATGGAAAC ATCCTGGTTr CCCTGCCTGG CCTCCTGGCA GC'TGCTAAT TCTCCATGTT TTAAACAAAG TAGAAAGTrA A'ITTAAGGCA 35 AATGATCAAC ACAAGTGAAA AAAAATATTA AAAAGGAATA TACAAACT'rr GGTCCTAGAA ATGGCACATT TGATTGCACT GGCCAGTGCA TTTGTfAACA GGAGTGTGAC CCTGAGAAAT TAGACGGCTC AAGCACTCCC AGGACCATGT CCACCCAAGT CTCTTGGGCA TAGTGCAGTG TCAATTCTTC CACAATATGG GGTCATTTGA TGGACATGGC CTAACTGCCT GTGGGTL1CTC TCTTCCTG'IT GTTGAGGCTG AAACAAGAGT GCTGGAGCGA TAATGTGTCC ATCCCCCTCC CCAGTCTTCC CCCC'ITGCCC CAACATCCGT CCCACCCAAT GCCAGGTGGT 40 TCCTTGTAGG GAAATITAC CGCCCAGCAG GAAC'ITATAT CTCTCCGCTG TAACGGGCAA AAGTI'TCAAG TGCGGTGAAC CCATCATI7AG CTGTGGTGAT CTGCCTGGCA TCGTGCCACA GTAGCCAAAG CCTCTGCACA GGAGTGTGGG CAACTAAGGC TGCTGACMT GAAGGACAGC CTCACTCAGG GGGAAGCTAT TTGCTCTCAG CCAGGCCAAG AAAATCCTGT TTCrrTGGAA TCGGGTAGTA AGAGTGATCC CAGGGCCTCC AATTGACACT GCTGTGACTG AGGAAGATCA AAATGAGTGT CTCTC'TGG AGCCAC'TrC CCAGCTCAGC CTCTCCTCTC 45 CCAGTITCTT CCCATGGGCT ACTCTCTGTT CCTGAAACAG TTCTGGTGCC TGATTrCTGG CAGAAGTACA GCTTCACCTC 'ITCCITTTCC TTCCACATTG ATCAAGTTGT TCCGCTCCTG TGGATGGGCA CATI7GCCAGC CAGTGACACA ATGGC'ITCCT TCCTCCTTC CTTCAGCATT TAAAATGTAG ACCCTCTrC A'ITCTCCGTTr CCTACTGCTA TGAGGCTCTG AGAAACCCTC AGGCC'ITTGA GGGGAAACCC TAAATCAACA AAATGACCCT GCTAT7GTCT GTGAGAAGTC AAGTTATCCT GTGTCTrAGG CCAAGGAACC TCACTGTGGG TTCCCACAGA 50 GGCTACCAAT TACATGTATC CTACTCTCGG GGCTAGGGGT TGGGGTGACC CTGCATGCTG TGTCCCTAAC CACAAGACCC CCTlC'ITTCT TCAGTGGTGT TCTCCATGTC C'ITGTACAA GGAGAAGAAA GTAATGACAA AATACCTGTG GCC'FrGGGCC TCAAGGAAAA GAATCTGTAC CTGTCCTGCG TGTITGAAAGA TGATAAGCCC ACTCTACAGC TGGAGGTAAG TGAATGCTAT GGAATGAAGC CCTTCTCAGC CTCCTGCTAC CACTTArrTCC CAGACAATTC ACCTITCTCCC CGCCCCCATC CCTAGGAAAA GCTGGGiAACA GGTCTA'TrTG ACAAGTYJTG 55 CATTAATGTA AATAAATIA ACATAATI= TAACTGCGTG CAACCTI'CAA TCCTGCTGCA GAAAATTAAA TCAYI11GCC GATGTTATTA TGTCCTACCA TAGITrACAAC CCCAACAGAT TATATATTGT TAGGGCTGCT CTCAMI1GAT AGACACC'I1G GGAAATAGAT GAC'ITAAAGG GTCCCATTAT CACGTCCACT CCACTCCCAA AATCACCACC ACTATCACCT CCAGCTCT CAGCAAAAGC TTCA'TrTCCA AGTIGATGTC ATTCTAGGAC CATAAGGAAA AATACAATAA AAAGCCCCTG GAAACTAGGT ACTrCAAGAA GCTCTAGCTT AAT=~CACC 60 CCCCCAAAAA AAAAAAATTC TCACCTACAT TATGCTCCTC AGCA T7GGC ACTAAG=FT AGAAAAGAAG AAGGGCTCTT1 TTAATAATCA CACAGAAAGT TGGGGGCCCA GTTACAACTC AGGAGTCTGG CTCCTGATCA TGTGACCTGC TCGTCAGYI17 CC'ITTCTGGC CAACCCAAAG AACATCTTTC CCATAGGCAT CTTTGTCCCT TGCCCCACAA AAATTCTTCT TTCTCTTTCG CTGCAGAGTG TAGATCCCAA AAATIrACCCA AAGAAGAAGA TGGAAAAGCG ATITGTCTTC AACAAGATAG AAATCAATAA CAAGCTGGAA '1TTGAGTCTG CCCAGTTCCC 65 CAACTGGTAC ATCAGCACCT CTCAAGCAGA AAACATGCCC GTCT'FCCTGG GAGGGACCAA AGGCGGCCAG GATATAACTG ACTTCACCAT GCAATTGTG TCTTCCTAAA GAGAGCTGTA CCCAGAGAGT CCTGTGCTGA WO 00/62736 PCT/USOO/08020 226 ATGTGGACTC AATCCCTAGG GCTGGCAGAA AGGGAACAGA AAGGTI=G AGTACGGCTA TAGCCTGGAC TTTCCTGTTG TCTACACCAA TGCCCAACTG CCTGCCTTAG GGTAGTGCTA AGAGGATCTC CTGTCCATCA GCCAGGACAG TCAGCTCTCT CC'TTTCAGGG CCAATCCCCA GCCCTITGT TGAGCCAGGC CTCTCTCACC TCTCCTACTC AC'ITAAAGCC CGCCTGACAG AAACCACGGC CACATI1GGT TCTAAGAAAC CCTCTGTCAT 5 TCGCTCCCAC ATTCTGATGA GCAACCGCTr CCCTATTTAT TTATITA TfT GTGTrTGT TTTGArrTCAT TGGTCTAATT TATTCAAAGG GGGCAAGAAG TAGCAGTGTC TGTAAAAGAG CCTAG'TI AATAGCTATG GAATCAATTC AATTFGGACT GGTGTGCTCT CT~AAATCA AGTCCT~AA 'ITAAGACTGA AAATATATAA GCTCAGATTA TTTAAATGGG AATA'I=ATA AATGAGCAAA TATCATACTG TTCAATGGTF CTGAAATAAA CT'rCACTGAA GAAAAAAAAA AAAGGGTCTC TCCTGATCAT TGACTGTCTG GATrTGACACT GACAGTAAGC 10 AAACAGGCTG TGAGAGTTCT TGGGACTAAG CCCACTCCTC A TGCTGAGT GCTGCAAGTA CCTAGAAATA TCCTTrGGCCA CCGAAGACTA TCCTCCTCAC CCATCCCCTI' TA'rrTCcrrG 'ITCAACAGAA GGATATTCAG TGCACATCTG GAACAGGATC AGCTGAAGCA CTGCAGGGAG TCAGGACTGG TAGTAACAGC TACCATGATr TATCTATCAA TGCACCAAAC ATCTGTTGAG CAAGCGCTAT GTACTAGGAG CTGGGAGTAC AGAGATGAGA ACAGTCACAA GTCCCTCCTC AGATAGGAGA GGCAGCTAGT TATAAGCAGA ACAAGGTAAC ATGACAAGTA 15 GAGTAAGATA GAAGAACGAA GAGGAGTAGC CAGGAAGGAG GGAGGAGAAC GACATAAGAA TCAAGCCTAA AGGGATAAAC AGAAGA'TrC CACACATGGG CTGGGCCAAT TGGGTGTCGG TTACGCCTGT AATCCCAGCA C=~GGGTGG CAGGGGCAGA AAGATCGC'IT GAGCCCAGGA GT7CAAGACC AGCCTGGGCA ACATAGTGAG ACTCCCATCT CTACAAAAAA TAAATAAATA AATAAAACAA TCAGCCAGGC ATGCTGGCAT GCACCTGTAG TCCTAGCTAC TrGGGAAGCT GACACTGGAG GATrGC2TTGA GCCCAGAAGT TCAAGACTGC AGTGAGCTTA 20 TCCGTTGACC TGCAGGTCGA C ACAAACCT TCGAGGCAAA AGGCAAAAAA GGCTGCTCTG GGATTCTCTT CAGCCAATCT TCAATGCTCA AGTGTCTGAA GCAGCCATGG CAGAAGTACC TAAGCTCGCC AGTGAAATGA TGGCTTAT11A CAGTGGCAAT GAGGATGACT TG'rrCITrGA AGCTGATGGC CCTAAACAGA TGAAGTGCTC CTTCCAGGAC CTGGACCTCT GCCCTCTGGA TGGCGGCATC CAGCTACGAA TCTCCGACCA CCACTACAGC AAGGGCYICA GGCAGGCCGC GTCAGTTG Pr GTGGCCATGG ACAAGCTGAG GAAGATGCTG GTTCCCTGCC 25 CACAGACCTT CCAGGAGAAT GACCTGAGCA CC=CTITCC CTTCATCM~ GAAGAAGAAC CTATCTTCTT CGACACATGG GATAACGAGG CTrATGTGCA CGATGCACCT GTACGATCAC TGAACTGCAC GCTCCGGGAC TCACAGCAAA AAAGCTrGGT GATGTCTGGT CCATATGAAC TGAAAGCTCT CCACCTCCAG GGACAGGATA TGGAGCAACA AGTGGTGTTC TCCATGTCCT TTGTACAAGG AGAAGAAAGT AATGACAAAA TACCTGTGGC CTTGGGCCTC AAGGAAAAGA ATCTGTACCT GTCCTGCGTG TTGAAAGATG ATAAGCCCAC TCTACAGCTG 30 GAGAGTGTAG ATCCCAAAAA TTACCCAAAG AAGAAGATGG AAAAGCGATT TGTCTTCAAC AAGATAGAAA TCAATAACAA GCTGGAA'TrT GAGTCTGCCC AG'ITCCCCAA CTGGTACATC AGCACCTCTC AAGCAGAAAA CATGCCCGTC TTCCTGGGAG GGACCAAAGG CGGCCAGGAT ATAACTGACT TCACCATGCA A1TGTGTCT TCCTAAAGAG AGCTGTACCC AGAGAGTCCT GTGCTGAATG TGGACTCAAT CCCTAGGGCT GGCAGAAAGG GAACAGAAAG GTTMTGAGT ACGGCTATAG CCTGGACTTF CCTGTTGTCT ACACCAATGC CCAACTGCCT 35 GCCTI'AGGGT AGTGCTAAGA GGATCTCCTG TCCATCAGCC AGGACAGTCA GCTCTCTCCT TTCAGGGCCA ATCCCAGCCC T=TTGAG CCAGGCCTCT CTCACCTCTC CTACTCACIT AAAGCCCGCC TGACAGAAAC CAGGCCACAT 1T~GGTTCTA AGAAACCCTC CTCTGTCATT CGCTCCCACA TT1CTGATGAG CAACCGCTI'C CCTATATT TAMIATTG 1TrGTTTGTT TrGATTCATT GGTCTAA'1 ATI'CAAAGGG GGCAAGAAGT AGCAGTGTCT GTAAAAGAGC CTAGTflTA ATAGCTATGG AATCAATTCA ATTTGGACTG GTGTGCTCTC 40 TT-7AAATCAA GTCCI=AAT TAAGACTGAA AATATATAAG CTCAGATTAT TTAAATGGGA ATAITTATAA ATGAGCAAAT ATCATACTGT TCAATGGTTC TCAAATAAAC I17CACT CTGGCAGGAG TAGCAGCTGC CCCTTGGCGC GACTGCTGGA GCCGCGAACT AGAGAAACAC AGACACGCCT CATAGAGCAA CGGCGTCTCT CGGAGCGTGG AGCCCGCCAA GCTCGAGCTG AGC1TCGCT TGCCGTCCAC CACTGCCCAC ACTGTCGTIF GCTGCCATCG CAGACCTGCT GCTGAC'ITCC ATCCCTCTGG ATCCGGCAAG GGCCTGCGAT TTTGACAATG 45 TCAAGAYITA CCGTATATCC CTGTTTGT GGATACACCA GTGACGTCCA C'ITCTAGAAG ACAAAGTT1AT ATI'ACTI'AAA CAACCAAAGA TATGAAACTA TCCATGAAGA ACAATATTAT CAATACACAG CAGTCT1TMG TAACCATGCC CAATGTGATI' GTACCAGATA TITGAAAAGGA AATACGAAGG ATGGAAAATG GAGCATGCAG CTCCTTrfCT GAGGATGATG ACAGTGCCTC TACATCTGAA GAATCAGAGA ATGAAAACCC TCATGCAAGG GG'I1CC'TA GTATAAGTC ACTCAGAAAG GGAGGACCAT CACAGAGGGA GCAGTACCTG CCTGGTGCCA 50 M~CCATMT TAATGTGAAC AACAGCGACA ATAAGGACCA GGAACCAGAA GAAAAAAAGA AAAAGAAAAA AGAAAAGAAG AGCAAGTCAG ATGATAAAAA CGAAAATAAA AACGACCCAA AGAAGAAGAT GGAAAAGCGA ATGGCCAAAG TTCCAGACAT GTTTGAAGAC CTGAAGAACT GTTACAGTGA AAATGAAGAA GACAGTTCCT CCATTGATCA TCTGTCTCTG AATCAGAAAT CCTTCTATCA TGTAAGCTAT GGCCCACTCC ATGAAGGCTG CATGGATCAA TCTGTGTCTC TGAGTATCTC TGAAACCTCT AAAACATCCA AGC'I1ACC'IT CAAGGAGAGC 55 ATGGTGGTAG TAGCAACCAA CGGGAAGGI1 CTGAAGAAGA GACGGTrGAG 'ITrAAGCCAA TCCATCACTG ATGATGACCT GGAGGCCATC GCCAATGACT CAGAGGAAGA AATCATCAAG CCTAGGTCAG CACCYITTAG CTTCCTGAGC AATGTGAAAT ACAACTTTAT GAGGATCATC AAATACGAAT TCATCCTGAA TGACGCCCTC AATCAAAGTA TAATTCGAGC CAATGATCAG TACCTCACGG CTGCTGCATT1 ACATAATCTG GATGAAGCAG TGAAA=TGA CATGGGTGCT TATAAGTCAT CAAAGGATGA TGCTAAAATT ACCGTGATTC TAAGAATCTC 60 AAAAACTCAA TTGTATGTGA CTGCCCAAGA TGAAGACCAA CCAGTGCTGC TGAAGGAGAT GCCTGAGATA CCCAAAACCA TCACAGGTAG TGAGACCAAC CTCCTCTTCT TCTGGGAAAC TCACGGCACT AAGAACTATT TCACATCAGT TGCCCATCCA AACTTGTTTA TTGCCACAAA GCAAGACTAC TGGGTGTGCT TGGCAGGGGG GCCACCCTCT ATCACTGACT YI'CAGATACT GGAAAACCAG GCGTAGGTCT GGAGTCTCAC 'rrGTCTCACT TGTGCAGTGT TGACAGTTCA TATGTACCAT GTACATGAAG AAGCTAAATC CTFACTGTF AGTCArrTGC 65 TGAGCATGTA CTGAGCCTrG TAATTCTAAA TGAATG IMrA CACTC TrTGT AAGAGTGGAA CCAACACTAA CATATAATGT TGTTATFAA AGAACACCCT ATA=T1GCA TAGTACCAAT CAYITAATT ATI'ATTCTTC WO 00/62736 PCT/USOO/08020 227 ATAACAA'1TT TAGGAGGACC AGAGCTACTG ACTATGGCTA CCAAAAAGAC TCTACCCATA TTACAGATGG GCAAATrAAG GCATAAGAAA ACTAAGAAAT ATGCACAATA GCAG117GAAA CAAGAAGCCA CAGACCTAGG ATI17CATGAT TCATrTCAA CTGMIGCCT TCTGC'1=A AGTTGCTGAT GAACTCTAA TCAAATAGCA TAAGTrCTG GGACCTCAGT 'PrTATCATrT TCAAAATGGA GGGAATAATA CCTAAGCCIT CCTGCCGCAA 5 CAGTTITA TGCTAATCAG GGAGGTCAT7 TIGGTAAAAT ACrTCTCGAA GCCGAGCCTC AAGATGAAGG CAAAGCACGA AATGTTATTT TAATTAT-F AITTATATAT GTATATAA ATATA'TTrAA GATAATTATA ATATACTATA TITATGGGAA CCCCTTCATC CTCTGAGTGT GACCAGGCAT CCTCCACAAT AGCAGACAGT GY1TCTGGG ATAAGTAAGT TTGATTTCAT TAATACAGGG CATITTGGTC CAAGTTGTGC TTATCCCATA GCCAGGAAAC TCTGCATTCT AGTACTTGGG AGACCTGTAA TCATATAATA AATGTACAT~r AATTACCTTG 10 AGCCAGTAAT TGGTCCGATC TGACTCTT TT1GCCATTAA ACTTACCTGG GcATI1cTTGT TTCATTCAAT TCCACCTGCA ATCAAGTCCT ACAAGCTAAA AT17AGATGAA CTCAAC'TTrG ACAACCATAG ACCACTGTrA TCAAAACTTI' CTTCTGGA ATGTAATCAA TGTI'TCTTCT AGGTTCTAAA AATI'GTGATC AGACCATAAT GTTACATTAT TATCAACAAT AGTGA'ITGAT AGAGTGTTAT CAGTCATAAC TAAATAAAGC T7~GCAAGTGA GGGAGTCATI' TCATTGGCGT 'ITGAGTCAGC AAAGAAGTCA AG AGCTGCCAGC CAGAGAGGGA 15 GTCAnITCAT TGGCGT'TGA GTCAGCAAAG AAGTCAAGAT GGCCAAAGT-r CCAGACATGT TrGAAGACCT GAAGAACTGT TACAGTGAAA ATGAAGAAGA CAG'FrCCTCC ATTGATCATC TGTCTCTGAA TCAGAAATCC TTCTATCATG TAAGCTATGG CCCACTCCAT GAAGGCTGCA TGGATCAATC TGTGTCTCTG AGTATCTCTG AAACCTCTAA AACATCCAAG CTTACCTTCA AGGAGAGCAT GGTGGTAGTA GCAACCAACG GGAAGGTTCT GAAGAAGAGA CGGTTGAGTT TAAGCCAATC CATCACTGAT GATGACCTGG AGGCCATCGC CAATGACTCA 20 GAGGAAGAAA TCATCAAGCC TAGGTCATCA CCTMAGCT TCCTGAGCAA TGTGAAATAC AAC'TTTATGA GGATCATCAA ATACGAATTC ATCCTGAATG ACGCCCTCAA TCAAAGTATA ATTCGAGCCA ATGATCAGTA CCTCACGGCT GCTGCATTAC ATAATCTGGA TGAAGCAGTG AAA'TTrGACA TGGGTGC'ITA TAAGTCATCA AAGGATGATG CTAAAATT1AC CGTGATTCTA AGAATCTCAA AAACTCAATT GTATGTGACT GCCCAAGATG AAGACCAACC AGTGCTGCTG AAGGAGATGC CTGAGATACC CAAAACCATC ACAGGTAGTG AGACCAACCT 25 CCTCTTCTTC TGGGAAACTC ACGGCACTAA GAACTA'TrC ACATCAGTTG CCCATCCAAA CTTGTTATT GCCACAAAGC AAGACTACTG GGTGTGCTI7G GCAGGGGGGC CACCCTCTAT CACTGAC'= CAGATACTGG AAAACCAGGC GTAGGTCTGG AGTCTCACTT GTCTCACTTG TGCAGTGTTG ACAGTTCATA TGTACCATGT ACATGAAGAA GCTAAATCCT TTACTGTTAG TCATPTGCTG AGCATGTACT GAGCCTTGTA A FrCTAAATG AATGTrACA CTC'TrGTAA GAGTGGAACC AACACTAACA TATAATGTTG TrAIFAAAG AACACCCTAT 30 ATTGCATA GTACCAATCA TI1AATTAT TATTCT-rCAT AACAA'T=A GGAGGACCAG AGCTACTGAC TATGGCTACC AAAAAGACTC TACCCATAUT ACAGATGGGC AAATTAAGGC ATAAGAAAAC TAAGAAATAT GCACAATAGC AGTCGAAACA AGAAGCCACA GACCTAGGAT TTCATGAT CATITCAACT G=IGCCTVC TGCT1T7AAG TrGCTGATGA ACTCT7AATC AAATAGCATA AGT1TTCTGGG ACCTCAG'Tr TATCATTTTC AAAATGGAGG GAATAATACC TAAGCCTTCC TGCCGCAACA GTTI=ATG CTAATCAGGG AGGTCATTr 35 GGTAAAATAC TT1CTCGAAGC CGAGCCTCAA GATGAAGGCA AAGCACGAAA TGTTATflT TAATT'TAT TT1ATATATGT ATTTATAAAT ATA FITAAGA TAA FTATAAT ATACTATATT TATGGGAACC CCTTCATCCT CTGAGTGTGA CCAGGCATCC TCCACAATAG CAGACAGTGT TTTCTGGGAT AAGTAAGT GATTITCATTA ATACAGGGCA TIT7GGTCCA AGTFGTGCTT ATCCCATAGC CAGGAAACTC TGCATTCTAG TACTTGGGAG ACCTGTAATC ATATAATAAA TGTACATTAA YTACCTTGAG CCAGTAAITrG GTCCGATCT17 TGACTCT'17~ 40 GCCA11?AAAC TTACCTGGGC A11'CT7G FIT CATTCAATTC CACCTGCAAT CAAGTCCTAC AAGCTAAAAT TAGATGAACT CAACTITGAC AACCATGAGA CCACTGTAT CAAAACTTTC TITCTGGAA TGTAATCAAT GTTTC FTCTA GGTTCTAAAA ATTGTGATCA GACCATAATG TTACATTATT ATCAACAATA GTGATTGATA GAGTG'ITATC AGTCATAACT AAATAAAGCT TGCAACAAAA TI7CTCTG-3' (FRAG. NO:_)(SEQ. ID NO:2517) 5'-AAGCU-CTAC CCTAGTCTGG TGCTACACTT ACATYrGCTTA CATCCAAGTG TGGTTA'TrTC TGTGGCTCCT 45 GTTATAACTA TTATAGCACC AGGTCTATGA CCAGGAGAAT TAGACTGGCA 'ITAAATCAGA ATAAGAGATT YI'GCACCTGC AATAGACCTI' ATGACACCTA ACCAACCCCA TrATTTACAA TTAAACAGGA ACAGAGGGAA TACTF17ATCC AACTCACACA AGCTGTI=C CTCCCAGATC CATGCITI TGCGTTTA'IT ATT'I=AGA GATGGGGGCT TCACTATGTT GCCCACACTG GACTAAAACT CTGGGCCTCA AGTGAI17GTC CTGCCTCAGC CTCCTGAATA GCTGGGACTA CAGGGGCATG CCATCACACC TAGTTCAT'1T CCTCTATTTA AAATATACAT 50 GGC'ITAAACT CCAACTGGGA ACCCAAAACA TTCAT17GCT AAGAGTCTGG TG ITCTACCA CCTGAACTAG GCTGGCCACA GGAAYTATAA AAGCTGAGAA ATTCT17AAT AATAGTAACC AGGCAACATC A FTGAAGGCT CATATGTAAA AATCCATGCC TTCC'7TrC CCAATCTCCA 'TrCCCAAACT TAGCCACTGG 'FrCTGGCTGA GGCCTTACGC ATACCTCCCG GGGCTTGCAC ACAC=TCTT CTACAGAAGA CACACCTTGG GCATATCCTA CAGAAGACCA GGCTTCTCTC TGGTCCTTGG TAGAGGGCTA CTTTACTGTA ACAGGGCCAG GGTGGAGAGT 55 TCTCTCCTGA AGCTCCATCC CCTCTATAGG AAATGTGTTG ACAATAYTCA GAAGAGTAAG AGGATCAAGA C'rCITGTG CTCAAATACC ACTGTTCTCT TCTCTACCCT GCCCTAACCA GGAGCTTGTC ACCCCAAACT CTGAGGTGAT TTATGCCTTA ATCAAGCAAA CTTCCCTCTT CAGAAAAGAT GGCTCATIT CCCTCAAAAG TI7GCCAGGAG CTGCCAAGTA TTCTGCCAAT TCACCCTGGA GCACAATCAA CAAA'ITCAGC CAGAACACAA CTACAGCTAC TATTAGAACT ATTIATATrA ATAAATTCCT CTCCAAATCT AGCCCCT1'GA CTTCGGA1TT 60 CACGA1TITCT CCCTTCCTCC TAGAAACTFTG ATAAGTrTCC CGCGCT-FCCC 'TI=CTAAG ACTACATGT TGTCATCTTA TAAAGCAAAG GGGTGAATAA ATGAACCAAA TCAATAACT7 CTGGAATATC TGCAAACAAC AATAATATCA GCTATGCCAT CTTTCACTAT YI17AGCCAGT ATCGAGTTGA ATGAACATAG AAAAATACAA AACTGAATTC TI'CCCTGTAA ATTCCCCG1T 'TTGACGACGC ACTTGTAGCC ACGTAGCCAC GCCTACTFTAA GACAATTACA AAAGGCGAAG AAGACTGACT CAGGCITrAAG CTGCCAGCCA GAGAGGGAGT CA'ITTCATTG 65 GCGT'IGAGT CAGCAAAGGT ATTGTCCTCA CATCTCTGGC TATTAAAGTA T1TCTGTTG TTG~fTI1CT CMF1GGCTGT '1TCTCTCAC ATTGCCTTCT CTAAAGCTAC AGTCTCTCCT 'rrC TTCTT GTCCCTCCCT WO 00/62736 PCT/USOO/08020 228 GGTI'TGGTAT GTGACCTAGA ATI7ACAGTCA GATCAGAA AATGAITrCTC TCATI=GCT GATAAGGACT GATTCGTT ACTGAGGGAC GGCAGAACTA GTTTCCTATG AGGGCATGGG TGAATACAAC TGAGGCY-FcT CATGGGAGGG AATCTCTACT ATCCAAAATT AITAGGAGAA AATTGAAAAT T7CCAACTCT GTCTCTCTCT TACCTCTGTG TAAGGCAAAT ACCTFATTCT TGTGGTG'IM TTGTAACCTC TTCAAACTTT CATTGATrGA 5 ATGCCTGTTC TGGCAATACA TTAGGTTGGG CACATAAGGA ATACCAACAT AAATAAAACA TTCTAAAAGA AGITrACGAT CTAATAAAGG AGACAGGTAC ATAGCAAACT AATTCAAAGG AGCTAGAAGA TGGAGAAAAT GCTGAATGTG GACTAAGTCA TTCAACAAAG TTCAGGAA GCACAAAGAG GAGGGGCTCC CCTCACAGAT ATCTGGATTA GAGGCTGGCT GAGCTGATGG TGGCTGGTGT TCTCTGTrGC AGAAGTCAAG ATGGCCAAAG TTCCAGACAT GTI1?GAAGAC CTGAAGAACT GTTACAGGTA AGGAATAAGA 'TrTATCTCTIT GTGA'ITAAT 10 GAGGGTTTCA AGGCTCACCA GAATCCAGCT AGGCATAACA GTGGCCAGCA TGGGGGCAGG CCGGCAGAGG TTGTAGAGAT GTGTACTAGT CCTGAAGTCA GAGCAGGTTC AGAGAAGACC CAGAAAAACT AAGCATTCAG CATG'ITAAAC TGAGATTACA TTGGCAGGGA GACCGCCATT TTAGAAAAAT TA TITGAG GTCTGCTGAG CCCTACATGA ATATCAGCAT CAAUITAGAC ACAGCCTCTG TJGAGATCAC ATGCCCTGAT ATAAGAATGG GTTTTACTGG TCCATI7CTCA GGAAAACTI1G ATCTCATTCA GGAACAGGAA ATGGCTCCAC AGCAAGCTGG 15 GCATGTGAAC TCACATATGC AGGCAAATCT CACTCAGATG TAGAAGAAAG GTAAATGAAC ACAAAGATAA AATTACGGAA CATATTAAAC TAACATGATG FITCCAYI'AT CTGTAGTAAA TACTAACACA AACTAGGCTG TCAAAAT1T GCCTGGATAT 'ITTACTAAGT ATAAATTATG AAATCTG'1TT TAGTGAATAC ATGAAAGTAA TGTGTAACAT ATAATCTA'rT TGGTTAAAAT AAAAAGGAAG TGCTTCAAAA CCnITC'lf CTCTAAAGGA GC FTAACATT CTTCCCTGAA CTTCAATTAA AGCTC'ITCAA TTGTTAGCC AAGTCCAATT ITTACAGATA 20 AAGCACAGGT AAAGCTCAAA GCCTGTCTTG ATGACTACTA ATTCCAGA'rr AGTAAGATAT GAATTACTCT ACCTATGTGT ATGTGTAGAA GTCCTTAAAT 'I1CAAAGATG ACAGTAATGG CCATGTGTAT GTGTGTGACC CACAACTATC ATGGTCAT-FA AAGTACATTG GCCAGAGACC ACATGAAATA ACAACAATrA CATTCTCATC ATCTT~ATTTT GACAGTGAAA ATGAAGAAGA CAGTTCCTCC AITGATCATC TGTCTCTGAA TCAGGTAAGC AAATGACTGT AATTCTCATG GGACTGCTAT TCTTACACAG TGGTrTCTTC ATCCAAAGAG AACAGCAATG 25 AcTrGAATCT TAAATACTTT TG'II1ACCC TCACTAGAGA TCCAGAGACC TGTCTPTCAT TATAAGTGAG ACCAGCTGCC TCTCTAAACT AATAGTTGAT GTGCATTGGC TTCTCCCAGA ACAGAGCAGA ACTATCCCAA ATCCCTGAGA ACTGGAGTCT CCTGGGGCAG G = CATCAG GATG'rrAGTT ATGCCATCCT GAGAAAGCCC CGCAGGCCGC TTCACCAGGT GTCTGTCTCC TAACGTGATG TGITFGTGG ~r GTCTTCTCTG ACACCAGCAT CAGAGGTTrAG AGAAAGTCTC CAAACATGAA GCTGAGAGAG AGGAAGCAAG CCAGCTGAAA GTGAGAAGTC 30 TACAGCCACT CATCAATCTG TGTTATI'GTG 1TTGGAGACC ACAAATAGAC ACTATAAGTA CTGCCTAGTA TGTCTTCAGT ACTGGCTTTA AAAGCTGTCC CCAAAGGAGT AT11?CTAAAA TATITTGAGC ATTGTTAAGC AGATTTTAA CCTCCTGAGA GGGAACTAAT TGGAAAGCTA CCACTCACTA CAATCATrGT TAACCTATI17 AGTTACAACA TCTCATT GAGCATGCAA ATAAATGAAA AAGTCTCCT AAAAAAATCA TCTITTATC CTGGAAGGAG GAAGGAAGGT GAGACAAAAG GGAGAGAGGG AGGGAAGCCT AATGAAACAC CAG FTACCTA 35 AGACCAGAAT GGAGATCCTC CTCACTACCT CTGTTGAATA CAGCACCTAC TGAAAGAACT TTCATrCCCT GACCATGAAC AGCCTCTCAG C'ITCTG=Ir CCTTCCTCAC AGAAATCCITr CTATCATGTA AGCTATGGCC CACTCCATGA AGGCTGCATG GATCAATCTG TGTCTCTGAG TATCTCTGAA ACCTCTAAAA CATCCAAGCT TACCTTCAAG GAGAGCATGG TGGTAGTAGC AACCAACGGG AAGGTTCTGA AGAAGAGACG G'VrGAdTTTA AGCCAATCCA TCACTGATGA TGACCTGGAG GCCATCGCCA ATGACTCAGA GGAAGGTAAG GGGTCAAGCA 40 CAATAATATC TTfCTTAC AGITVAAGC AAGTAGGGAC AGTAGAAT' AGGGGAAAAT TAAACGTGGA GTCAGAATAA CAAGAAGACA ACCAAGCATr AGTCTGGTAA CTATACAGAG GAAAA FTAAT TrTATCCTT CTCCAGGAGG GAGAAATGAG CAGTGGCCTG AATCGAGAAT ACTTGCTCAC AGCCA'I7ATT TCITrAGCCAT ATrGTAAAGG TCGTGTGACT 'TrAGCCTrr CAGGAGAAAG CAGTAATAAG ACCACT7ACG AGCTATGTTC CTCTCATACT AACTATGCCT CCT7GGTCAT GTTACATAAT CTMTCGTGA TTCAG FITCC TCTACTGTAA 45 AATGGAGATA ATCAGAATCC CCCACTCA117 GGATTGT7GT AAAGAYrAAG AGTCTCAGGC TrACAGACT GAGCTAGCTG GGCCCTCCTG ACTG'ITATAA AGA'ITAAATG AGTCAACATC CCCTAAC'JTC TGGACTAGAA TAATGTCTGG TACAAAGTAA GCACCCAATA AATGTTAGCT ATrACTATCA FTA FTArAT TAT TTTE TITTTT=G AGATGGAGTC TGGCTCTGTC ACCCAGGCTG GAGTGCAGTG GCACAATCTC GGCTCACTGC AAGCTCTGCC TCCTGGGTrC ATGCCA I7CT CCTGCCTCAG CCTCCCGAGT AAGCTGGGAA TACAGGCACC 50 CGCCACTGTT CCCGGCTAAT T TITGTATT TTAGTAGAG ACGGAGTC ACCGTGGTCT CCATCTCCTC GTGATCCACC CAC=TGGCC TCCCAAAGTG CCGGGATTAC AGGCGTGAGC CACCGCGCCC GGCCTAP~rAT TATTATTATT ACTACTACTA CTACCTATAT GAATACTACC AGCAATACTA A TTATTAAT GACTGGATTA TGTCTAAACC TCACAAGAAT CCTACCTI'CT CA1T=ACAT AAAAGGAAAC TAAGCTCATT GAGATAGGTA AACTGCCCAA TGGCATACAT CTGTAAGTGG GAGAGCCTCA AATCTAA'I1C AG'ITCTACCT GAGTAAAAAA 55 ATCATGG'1TT CTCCTCCATC CC'ITTACTGT ACAAGCCTCC ACATGAACTA TAAACCCAAT ATTCCTGTIT TTAAGATAAT ACCTAAGCAA TAACGCATGT TCACCTAGAA GGTITAAAA TGTAACAAAA TATAAGAAAA TAAAAATCAC TCATATCGTC AGTGAGAGTT TACTACTGCC AGCACTATGG TATG TrTCCT TAAAATC'Tr GCTATACACA TACCTACATG TGAACAAATA TGTCTAACAT CAAGACCACA CTA'1TTACAA ='TATATCC AGCTTCTT ACTTAGCAAT GTATTGAGGA CAT1TAGAG TGCCCGTIT TCACCATTAT AAGCAATGCA 60 ACAATGAACA TCTGTATAAA TAAATA FTCA MTCTCTCAC CCTTTA TTC C'IAGAATAT ATTCCTAGAA GTAGAATTTC CCAGAGCCAT GAGGATGT GACGCTATTG ATATGTGCCA CTrTGCACTC TCTGTGACAT ATATAATI'AT 'TTTAATGCA TTCA FTT TCTCAGAGTG CATCGTG AAAACATAGA CGGGAAATAC TGGTAGTCTT CCTTGTCAGT TAGAAACACC CAAACAATGA AAAATGAAAA AGTT1GCACAA ATAGTCTCTA AAAACAATGA AACTATTGCC TGAGGAA317G AAGTIT7AAAA AGAAGCACAT AAGCAACAAC AAGGATAATC 65 CTAGAAAACC AGTTCTGCTG ACTGGGTGAT TL7CAC'TrCTC TYGCT'FCCT CATCTGGATT GGAATATTCC TAATACCCCC TCCAGAACTA T1TCCCTGT TTGTACTAGA CTGTGTATAT CATCTGTGTT TGTACATAGA WO 00/62736 PCT/USOO/08020 229 CATTAATCTG CACTTGTGAT CATGGTTA GAAATCATCA AGCCTAGGTC ATCACC'Ir AGCTTCCTGA GCAATGTGAA ATACAACTrT ATGAGGATCA TCAAATACGA ATTCATCCTG AATGACGCCC TCAATCAAAG TATAATTCGA GCCAATGATC AGTACCTCAC GGCTGCTGCA TTACATAATC TGGATGAAGC AGGTACATTA AAATGGCACC AGACAM~CT GTCATCCTCC CCTCCTICA TITACTI'ATT TATTAMC AATC'ITTCTG 5 CTTGCAAAAA ACATACCTCT TCAGAGTTCT GGGTTGCACA ATrCl7CCAG AATAGCTTGA AGCACAGCAC CCCCATAAAA ATCCCAAGCC AGGGCAGAAG GTTCAACTAA ATCTGGAAGT TCCACAAGAG AGAAGTTCC TATC'TGAG AGTAAAGGGT TGTGCACAAA GCTAGCTGAT GTACTACCTC TTGGTT= TCAGACATTC TTACCCTCAA TI=AAAACT GAGGAAACTG TCAGACATAT TAAATGATTT ACTCAGA IT ACCCAGAAGC CAATGAAGAA CAATCACTCT CCTIAAAAA GTCTGTTGAT CAAACTCACA AGTAACACCA AACCAGGAAG 10 ATC=~ATTA TCTCTGATAA CATA=GTG AGGCAAAACC TCCAATAAGC TACAAATATG GC11?AAAGGA TGAAGTI1AG TGTCCAAAAA C'IT'ATCAC ACACATCCAA TIICATGGC GGACATG'TTT TAGTTTCAAC AGTATACATA T1TCAAAGG TCCAGAGAGG CAATI=GCA ATAAACAAGC AAGACTITP CTGATTGGAT GCACTTCAGC TAACATGCTT TCAACTCTAC A ITTACAAAT TAT=EGTGT TCTATTITC TACTTAATAT TATJTCTGCA ATIICCCAA TATTGACATC GTGTATGTAT 17GCCATrT TAATATCACT AGACAATTCA 15 ATCAGGTTGC TACGTTGGTC CCTTGGGTI1' ACTCTAAATA GCTTGATTGC AAATATCTI' GTATATATTA TTGTIT=TC TCCTATCITrG TAAMTTT GAGCACATCC CAAAGAGGAA TGCCTAGATC AATGGGCACA AATAAThTGA CAGCTCTFTAT TAAACATTAT TCTGTAAGTA AAAACTGAAC TACTITTCAG TATCACTAGC AACATATGAG TGTATCAGCT TCCTAAACCC CTCCATGTTA GGTCATTATG AACTTATGAT CTAACAAATT ACAGGGTCTr ATCCCACTAA TGAAATTATA AGAGATrCAA CACT1CA GCCCCGAAGG A'YrCATTCAA 20 CGTAGAAAAT TCTAAGAACA TTAACCAAGT AT=ACCTGC CTAGTGAGTG TGGAAGACAT TGTGAAGGAC ACAAAGATGT ATAGAATTCC ATTCCTGACT TCCAGGTATT TACACCATAG GTGGGGACCT AACTACACAC ACACACACAC ACACACACAC ACACACACAC ACCATGCACA CACAATCTAC ATCAACACI1' GATITIATAC AAATACAATG AATTTACT F[ CTITIGG117 CTTCTCT7CA CCAGTGAAAT TTGACATGGG TGCTTATAAG TCATCAAAGG ATGATGCTAA AATrACCGTG A'I1CTAAGAA TCTCAAAAAC TCAAYTGTAT GTGACTGCCC 25 AAGATGAAGA CCAACCAGTG CTGCTGAAGG TCAGTI'GTCC T17GTCTCCA ACTTACC'rrC ATACATCT CATATG'ITTG TAAATAAGCC CAATAGGCAG ACACCTCTAA CAAGGTGACA CTGTCCTCTT TCCTTCCTAC CACAGCCCCC ACCTACCCAC CCCACTCCCA TTGATTCCAG AGGCGTGCCT AGGCAGGATC TATGAGAAAA TATAACAGAG AGTAAGAGGA AAA'rrACCTr CTrTC'Tr CC'TrCCCTG CCTGACC117A TTCACCTCCC ATCCCAGAGC ATCCATTAT TCCA'rrGATC TITACTGACA TCTATTATCT GACCTACACA ATACTAGACA 30 TTAGGACAAT GTGGCCTGCC TCCAAGAAAC TCAAATAAGC CAACTGAGAT CAGAGAGGAT TAATCACCTG CCAATGGGCA CAAAGCAACA AGCTGGGAGC CAAGTCCCAA AATGGGGCCT GCTGC'I7CCA GTTCCCCTCT CTCTGCATTG ATGTCAGCAT TATCC'ITCGT CCCAGTCCTG TCTCCACTAC CAC'FCCCC CTCAAACACA CACACACACA ACAGCCTT1AG ATG1T1CTC CACTGATAAG TAGGTGACTC AATTTGTAAG TATATAATCC AAGACCTTCT AT7CCCAAGT AGAA'ITTATG TGCCTGCCTG TGCTITCTA CCTGGATCAA GTGATGTCTA 35 CAGAGTAGGG CAGTAGCTTC ATTCATGAAC TCATTCAACA AGCATFATTC ACTGAGAGCC 'FrGTAPT'IT CAGGCATAGT GCCAACAGCA GTGTGGACAG TGGTGCATCA AAGCCTCTAG TCTCATAGAA C'ITAGTCTTC TGGAGGATAT GGAAAACAGA CAACCCAAAC AACCAACAAA AGAGCAAGAT GCTGCAAAAA AAAAAAAAAT GAATAGGGTG CTAAGATAGA GAAAAGTGGG AGAGTGCTAT TT1AGACAAAG TGGTAAAAAC AAAGCCCCTT GTGAGATGAG AGCTGCCGAC AGAGGGGGCG GGTCATGGTT GTGGGTIT GGGTAGGACA TTCAGAGGAG 40 GGGGCGGGTC GTGG317GTGG GTTTGGGT AGGACAT7CA GAGGAGGGGG CGGGTCGTGG 'FrGTGGGTIT TTGGGTAGGA CATTCAGAGG AGGGGGCGGG TCGTGGTrGT GGG~T=GG GTAGGACATT CAGAGGAGGG GGCGGGTCGT GGTTGTGGGT TITTTGGGACA TTCAGAGGAG TCTGAATGCA CCCAGGCCTA CAAC'ITCAAG ATGGTAAAGG ACAGCTCCAA GGATCAGAAG AAGCA'rTC'rr GGAACTGGGG CA'rTrGAGA AGGAGGAAAA ATATGCAGAG ACTAGTGCT GCAGAGC'ITG CATGGA'rr TCATGAGG TACAATGAAA ACCCATTrAAT 45 GGG I=fCACA CAGTGCAATG GCCTGACCTC ACTTATA'Tr CCTAAAATAG AAAACAGATC AGAAGGAAGG CAATAGAGAA GCAGAAAGTC CAATGAGGAG GTTTCACAGC AGTCATGGGG GTGGGGTAAG GAAAAGAAGT GGAAAGAAAC AGACAGAAT[ GGGTrFATA'rT TI'GGAGATAG AACCAACAGA AGGAAGAGGA GAAACAACAT TTACTGAGAA GGGAAAAAGT AGGAGAGGAA TAGG1T~GGG AAATAAATCC TGCTGACATT1 GGAAACCCCA AGGAAGCCTC AAAAGTATAT TrACrrGCTr TAGA=~AAA AGAATAGGAA AGAAGCATCT CAACTTGGAA 50 TTTGAAATCT ATITCCAT AAAAGTATTG TTAAATTCTA CTCATACTCA CAAGAAAAGT ACATTCTAAA GAGTATAT-TG AAAGAGTA CTGATATACT TAGGAA'TIT GTGTGTATGT GTGTGTGTGT ATGTGTGTGT GTGTGTTTAA CC'MCAATrG TTGACTTAAA TACTGAGATA AATGTCATCT AAATGCTAAA TTGAT11?CCC AAAGGTATGA TrGFrCACT TGGAGATCAA AATGTAGG GGGCTI7AGAA TCACTGTAGT GCTCAGA'TTT GATGCAAAAT GTCTTAGGCC TATGTTGAAG GCAGGACAGA AACAATGTI'T CCCTCCTACC TGCCTGGATA 55 CAGTAAGATA CTAGTGTCAC TGACAATCTT CATAACTAAT ITrAGATCTCT CTCCAATCAA CTAAGGAAAT CAACTCTFAT TAATAGACTG GGCCACACAT CTACTAGGCA TGTAATAAAT GCTI1GCTGAA TGAACAAATG AATGAAGAGC CTATAGCATC ATGTTACAGC CATAGTCCTA AAGTGGTGYI' TCTCATGAAG GCCAAATGCT AAGGGATTGA GCTTCAGTCC T'TflCTAAC ATCTTG'rTCT CTAACAGAAT TCTCTTC'ITT TCTTCATAGG AGATGCCTGA GATACCCAAA ACCATCACAG GTAGTGAGAC CAACCTCCTC TTCTTCTGGG AAACTCACGG 60 CACTAAGAAC TA'TrCACAT CAGTTGCCCA TCCAAACTTG 'IMrATTGCCA CAAAGCAAGA CTACTGGGTG TGCTTfGGCAG GGGGGCCACC CTCTATCACT GAC1TTCAGA TACTGGAAAA CCAGGCGTAG GTCTGGAGTC TCACTTGTCT CACTTGTGCA GTGTTGACAG TTCATATGTA CCATGTACAT GAAGAAGCTA AATCCTITAC TGTTAGTCAT TTGCTGAGCA TGTACTGAGC CTTGTAATTC TAAATGAATG 'ITTACACTCT TTGTAAGAGT GGAACCAACA CTAACATATA ATGTrGTTAT TJ7AAAGAACA CCCTATAM~ TGCATAGTAC CAATCATIT 65 AATTA ITATT CT-FCATAACA A'T1'AGGAG GACCAGAGCT ACTGACTATG GCTACCAAAA AGACTCTACC CATATTACAG ATGGGCAAAT TAAGGCATAA GAAAACTAAG AAATATGCAC AATAGCAG FT GAAACAAGAA WO 00/62736 PCT/USOO/08020 230 GCCACAGACC TAGGAMICA TGATCATr TCAACTGn7~ GCCT-fCTGCT 'TTfAAG'ITGC TGATGAACTC FrAATCAAAT AGCATAAGTI' TCTGGGACCT CAG3TrATC ATITI'CAAAA TGGAGGGAAT AATACCTAAG CCTTCCTGCC GCAACAGMTITITTATGCTAA TCAGGGAGGT CATMTGGTA AAATACTTCT CGAAGCCGAG CCTCAAGATG AAGGCAAAGC ACGAAATGT7 ATITTAAT TA'rrA3TAT ATATGTATTT ATAAATATAT 5 TrAAGATAAT TATAATATAC TATA1TI7ATG GGAACCCCTr CATCCTCTGA GTGTGACCAG GCATCCTCCA CAATAGCAGA CAGTG'IIC. TGGGATAAGT AAG'IMGATr TCATTAATAC AGGGCA7 GGTCCAAGT7 GTGCTTATCC CATAGCCAGG AAACTCTGCA TI1CTAGTACT TGGGAGACCT GTAATCATAT AATAAATGTA CATTAATTAC CTrFGAGCCAG TAA'ITGGTCC GATCITTGAC TCTITGCCA TTAAACTTAC CTGGGCA ~rC TTGTITCATT CAATTCCACC TGCAATCAAG TCCTACAAGC TAAAATTAGA TGAACTCAAC TTTGACAACC 10 ATGAGACCAC TGTTATCAAA ACTrTTr= CTGGAATGTA ATCAATGTT CTTCTAGGTT GTAAAAATrG TGATCAGACC ATAATGTTAC ATI1ATTATCA ACAATAGTGA TTGATAGAGT GTTATCAGTC ATAACTAAAT AAAGCT'FGCA ACAAAATTCT CTGACACATA GTrA'rrCATT GCCTrAATCA TVA'IMrACT GCATGGTAAT TAGGGACAAA TGGTAAATGT TI'ACATAAAT AA'PrGTATTT AGTGTTACTr TATAAAATCA AACCAAGATr TTATA TTM TrCTCCTCTT TG'TAGCTGC CAGTATGCAT AAATGGCATr AAGAATGATA ATAMTCCGG 15 GTTCACTTAA AGCTCATATT ACACATACAC AAAACATGTG 'FrCCCATCTT TATACAAACT CACACATACA GAGCTACATT AAAAACAACT AATAGGCCAG GCACGGTGGC TCAGACCTGT AATCCCAGCA CTTTGGGAGG 3' (FRAG. NO: _) (SEQ. ID NO:2510) 5'-ACCAACCTCT TCGAGGCACA AGGCACAACA GGCTGCTCTG GGATTCTCTr CAGCCAATCT TCATTGCTCA AGTGTCTGAA GCAGCCATGG CAGAAGTACC TGAGCTCGCC AGTGAAATGA TGGCTTA'rrA CAGTGGCAAT 20 GAGGATGACT TGTTC3TTGA AGCTGATGGC CCTAAACAGA TGAAGTGCTC C'ITCCAGGAC CTGGACCTCT GCCCTCTGGA TGGCGGCATC CAGCTACGAA TCTCCGACCA CCACTACAGC AAGGGCTFCA GGCAGGCCGC GTCAGTTGYF GTGGCCATGG ACAAGCTGAG GAAGATGCTG GTrCCCTGCC CACAGACCTJ' CCAGGAGAAT GACCTGAGCA CCTI'CTrCC CTrCATC=r GAAGAAGAAC CTATCTCT7 CGACACATGG GATAACGAGG CTTATGTGCA CGATGCACCT GTACGATCAC TGAACTGCAC GCTCCGGGAC TCACAGCAAA AAAGCTTGGT 25 GATGTCTGGT CCATATGAAC TGAAAGCTCT CCACCTCCAG GGACAGGATA TGGAGCAACA AGTGGTG'I1C TCCATGTCCT TTGTACAAGG AGAAGAAAGT AATGACAAAA TACCTGTGGC CTTGGGCCTC AAGGAAAAGA ATCTGTACCT GTCCTGCGTG TTGAAAGATG ATAAGCCCAC TCTACAGCTG GAGAGTGTAG ATCCCAAAAA TTACCCAAAG AAGAAGATGG AAAAGCGATTI TGTC'rTCAAC AAGATAGAAA TCAATAACAA GCTGGAA3TJ7 GAGTCTGCCC AG317CCCCAA CTGGTACATC AGCACCTCTC AAGCAGAAAA CATGCCCGTC TI7CCTGGGAG 30 GGACCAAAGG CGGCCAGGAT ATAACTGACT TCACCATGCA A = GTGTCT TCCTAAAGAG AGCTGTACCC AGAGAGTCCT GTGCTGAATG TGGACTCAAT CCCTAGGGCT GGCAGAAAGG GAACAGAAAG G'TTTGAGT ACGGCTATAG CCTGGACTFI' CCTGTTGTCT ACACCAATGC CCAACTGCCT GCCTI'AGGGT AGTGCTAAGA GGATCTCCTG TCCATCAGCC AGGACAGTCA GCTCTCTCCT TrCAGGGCCA ATCCCCAGCC CT=TGTTGA GCCAGGCCTC TCTCACCTCT CCTACTCACT TAAAGCCCGC CTGACAGAAA CCACGGCCAC ATTTGGTFCT 35 AAGAAACCCT CTGTCATTCG CTCCCACATT CTGATGAGCA ACCGCr-rCCC TATTTAT7A TTTA3TTGTT TG'I=rGTTTr A'TCATTGGT CTAATTTA'1T CAAAGGGGGC AAGAAGTAGC AGTGTCTGTA AAAGAGCCTA G'TTTAATA GCTATGGAAT CAATlCAATT TGGACTGGTG TGCTCTC'T AAATCAAGTC CYIAATTAA GACTGAAAAT ATATAAGCTC AGATATA AATGGGAATA TTATAAATG AGCAAATATC ATACTGTTCA ATGGTTCTGA AATAAACTTC TCTGAAG-3' (FRAG. NO:_)(SEQ. ID NO:2511) 40 5'-AGAAAGAAAG AGAGAGAGAA AGAAAAGAAA GAGGAAGGAA GGAAGGAAGG AAGAAAGACA GGCTCTGAGG AAGGTGGCAG 'I17CCTACAAC GGGAGAACCA GTGG~rrAA'rr TGCAAAGTGG ATCCTGTGGA GGCANNCAGA GGAGTCCCCT AGGCCACCCA GACAGGGCT~r TAGCTATCT GCAGGCCAGA CACCAAATIT CAGGAGGGCT CAGTG'rrAGG AATGGATI'AT GGC'ITATCAA ATTCACAGGA AACTAACATG TTGAACAGCT =TAGATTTC CTGTGGAAAA TATAACTTAC TAAAGATGGA GTTCTrGTGA CTGACTCCTG ATATCAAGAT 45 ACTGGGAGCC AAATTAAAAA TCAGAAGGCT GCTI'GGAGAG CAAGTCCATG AAATGCTCTT TrrCCCACAG TAGAACCTAT TTCCCTCGTG TCTCAAATAC TTGCACAGAG GCTCACTCCC TI7GGATAATG CAGAGCGAGC ACGATACCTG GCACATACTA ATI1?GAATAA AATGCTGTCA AA'I17CCCATT1 CACCCATTCA AGCAGCAAAC TCTATCTCAC CTGAATGTAC ATGCCAGGCA CTGTGCTAGA CTI'GGCTCAA AAAGA1TCA G3TTCCTGGA GGAACCAGGA GGGCAAGGTT TCAACTCAGT GCTATAAGAA GTGTTACAGG CTGGACACGG TGGCTCACGC 50 CTGTAATCCC AACA'TI7GGG AGGCCGAGGC GGGCAGATCA CAAGGTCAGG AGATCGAGAC CATCCTGGCT AACATGGTGA AACCCTGTCT CTACTAAAAA TACAAAAAAT TAGCCGGGCG TTGGCGGCAG GTGCCTGTAG TCCCAGCTGC TGGGGAGGCT GAGGCAGGAG AATGGTGTGA ACCCGGGAGG CGGAACTTGC AGGGGGCCGA GATCGTGCCA CTGCACTCCA GCCTGGGCGA CAGAGTGAGA CTCTGTCTCA AAAAAAAAAA AAAAGTGY~rA TGATGCAGAC CTGTCAAAGA GGCAAAGGAG GGTGTTCCTA CACTCCAGGC ACTGTTCATA ACCTGGACTC 55 TCAT7CATrC TACAAATGGA GGGCTCCCCT GGGCAGATCC CTGGAGCAGG CAC'ITTGCTG GTGTCTCGGT TAAAGAGAAA CTGATAACTC UTGGTATTAC CAAGAGATAG AGTCTCAGAT GGATATTCTT ACAGAAACAA TATTCCCACT TIT7CAGAGT[T CACCAAAAAA TCATITTAGG CAGAGCTCAT CTGGCATTGA TCTGGTI'CAT CCATGAGATT GGCTAGGGTA ACAGCACCTG GTCT-rGCAGG GTTGTGTGAG C'FrATCTCCA GGGTTGCCCC AACTCCGTCA GGAGCCTGAA CCCTGCATAC CGTATG3TCT CTGCCCCAGC CAAGAAAGGT CAATTTTCTC 60 CTCAGAGGCT CCTGCAATTG ACAGAGAGCT CCCGAGGCAG AGAACAGCAC CCAAGGTAGA GACCCACACC CTCAATACAG ACAGGGAGGG CTATTGGCCC TTCATI7GTAC CCATATCC ATCTGTAAGT GGGAAGATTC CTAAACT7AA GTACAAAGAA GTGAATGAAG AAAAGTATGT GCATGTATAA ATCTGTGTGT C'rrCCACTIT GTCCCACATA TACTAAAT317 AAACATTC IT CTAACGTGGG AAAATCCAGT ATITAATGT GGACATCAAC TGCACAACGA TTGTCAGGAA AACAATGCAT A TTGCATGG TGATACATrT GCAAAATGTG TCATAGTTTG 65 CTACTCCTTG CCCT7CCATG AACCAGAGAA TTATCTCAGT TTAT-TAGTCC CCTCCCCTAA GAAG=TCCA CCAATACTCT 'TCCCCTr CCTTTAACTT GATTGTGAAA TCAGGTAT~rC AACAGAGAAA TI'TCTCAGCC WO 00/62736 PCT/USOO/08020 231 TCCTACTTCT GCTI=GAAA GCTATAAAAA CAGCGAGGGA GAAACTGGCA GATACCAAAC CTCTTCGAGG CACAAGGCAC AACAGGCTGC TCTGGGATI'C TC=CAGCCA ATCTrCATTG CTCAAGTATG AC'TrTAA.TCT TCCTTACAAC TAGGTGCTAA GGGAGTCTCT CTGTCTCTCT GCCTCTTTrGT GTGTATGCAT A'ITCTCTCTC TCTCTCTCIT TCTTTCTCTG TCTCTCCTCT CC'ITCCTCTC TGCCTCCTCT CTCAGCTIT TGCAAAAATG 5 CCAGGTGTAA TATAATGCTT ATGACTCGGG AAATATI'CTG GGAATGGATA CTGCTATCT AACAGCTGAC ACCCTAAAGG T7AGTGTCAA AGCCTCTGCT CCAGCTCTCC TAGCCAATAC ATTGCTAGTT GGGGTTTGGT T17AGCAAATG CTTCTCTA GACCCAAAGG AC FrCTCT CACACATrCA TTCATTTACT CAGAGATCAT TTCT'ITGCAT GACTGCCATG CACTGGATGC TGAGAGAAAT CACACATGAA CGTAGCCGTC ATGGGGAAGT CACTCATTYT CTCCYVITTA CACAGGTGTC TGAAGCAGCC ATGGCAGAAG TACCTGAGCT CGCCAGTGAA 10 ATGATGGCTT ATI7ACAGGTC AGTGGAGACG CTGAGACCAG TAACATGAGC AGGTCTCCTC TITCAAGAGT AGAGTGTTAT CTGTGCTTGG AGACCAGA117 TCCCCTAA ATTGCCTCTT TCAGTGGCAA ACAGGGTGCC AAGTAAATCT GA'1TAAAGA CTACTrCCC ATTACAAGTC CCTCCAGCCT TGGGACCTGG AGGCTATCCA GATGTGTTGT TGCAAGGGCT TCCTGCAGAG GCAAATGGGG AGAAAAGATT CCAAGCCCAC AATACAAGGA ATCCCTI'TGC AAAGTGTGGC TTGGAGGGAG AGGGAGAGCT CAGA7ITAG CTGACTCTGC TGGGCTAGAG 15 GTTAGGCCTC AAGATCCAAC AGGGAGCACC AGGGTGCCCA CCTGCC AGGC CTAGAATCTG CCTrCTGGAC TGYI7CTGCGC ATATCACTGT GAAACTTGCC AGGTGMICA GGCAGCT'IG AGAGGCAGGC TGITTGCAGT TYTCTTATGAA CAGTCAAGTC TTGTACACAG GGAAGGAAAA ATAAACCTGT TTAGAAGACA TAA FTGAGAC ATGTCCCTGT TITATTACA GTGGCAATGA GGATGACTTG TTCTTTGAAG CTGATGGCCC TAAACAGATG AAGGTAAGAC TATGGGTTTA ACTCCCAACC CAAGGAAGGG CTCTAACACA GGGAAAGCTC AAAGAAGGGA 20 GYrCTGGGCC ACTITGATGC CATGGTA=V TGTITAGAA AGAcTrAAc CTCTTCCAGT GAGACACAGG CTGCACCACT TGCTGACCTG GCCACT7GGT CATCATATCA CCACAGTCAC TCACTAACGT TGGTGGTGGT GGCCACACTT GGTGGTGACA GGGGAGGAGT AGTGATAATG TTCCCATTTC ATAGTAGGAA GACAACCAAG TCT'rCAACAT AAATITGATT ATCCTTIAA GAGATGGATT CAGCCTATGC CAATCACTTG AGYTAAACTC TGAAACCAAG AGATGATC'IT GAGAACTAAC ATATGTCTAC CCCTIIGAG TAGAATAGTT TITGCTACC 25 TGGGGTGAAG CTTATAACAA CAAGACATAG ATGATATAAA CAAAAAGATG AAYI'GAGACT TGAAAGAAAA CCATTCACTT GCTGTITGAC CTTGACAAGT CAT1TACCC GCT~GGACC TCATCTGAAA AATAAAGGGC TGAGCTGGAT GATCTCTGAG ATrCCAGCAT CCTGCAACCT CCAG~rCTGA AATATI=CA G'I1GTAGCTA AGGGCATTTG GGCAGCAAAT GGTCAT='T CAGACTCATC CTTACAAAGA GCCATci'FrAT ATT1CCTGCTG TCCCTrCTGT 'I=ATATGAT GCTCAGTAGC CTTCCTAGGT GCCCAGCCAT CAGCCTAGCT AGGTCAG117G 30 TGCAGGTTGG AGGCAGCCAC TITCTCTGG C'1TTATTA TTCCAGTTTG TGATAGCCTC CCCTAGCCTC ATAATCCAGT CCTCAATC F GTlAAAAACA TA'1TTCnrrA GAAGTITAA GACTGGCATA ACTrCTTGGC TGCAGCTGTG GGAGGAGCCC A'FrGGC'FGT CTGCCTGGCC 'TrTGCCCCCC ATI1GCCTCTT CCAGCAGCTT GGCTCTGCTC CAGGCAGGAA ATTCTCTCCT GCTCAACTT'T CTITTGTGCA C'FrACAGGTC TCTITAACTG TC'TrCAAGC CTTGAACCA TI1ATCAGCCT TAAGGCAACC TCAGTGAAGC CT7AATACGG AGCTTCTCTG 35 AATAAGAGGA AAGTGGTAAC ATFITCACAAA AAGTACTCTC ACAGGATITG CAGAATGCCT ATGAGACAGT GTTATGAAAA AGGAAAAAAA AGAACAGTGT AGAAAAATTG AATACTTGCT GAGTGAGCAT AGGTGAATGG AAAATGYI'AT GGTCATCTGC ATGAAAAAGC AAATCATAGT GTGACAGCAT TAGGGATACA AAAAGATATA GAGAAGGTAT ACATGTATGG TGTAGGTGGG GCATGTACAA AAAGATGACA AGTAGAATCG GGATTTATI1C TAAAGAATAG CCTGTAAGGT GTCCAGAAGC CACATTCTAG TCT7GAGTCT GCCTCTACCT GCTGTGTGCC 40 CTTGAGTACA CCCTI'AACCT CCTTGAGCTT CAGAGAGGGA TAATCT=IT ArTr7ArI ATITTAT=T GTT-ITGTrrr GTTTTGThT GTITATGAG ACAGAGTCTC ACTCTGTTGC CCAGGCTGGA GTGCAGTGGT ACAATCTTGG CTTACTGCAT CCTCCACCTC CTGAGTTCAA GCGATTCTCC TTCCTCAGTC TCCTGAATAG CTAGGAT7AC AGGTGCACCC CACCACACCC AGCTAATrTT TGTAYI1TIFA GTAGAGAAGG GGTITCGCCA TGTTGGCCAG GCTGG'ITTTG AAGTCCTGAC CTAAATGATT CATCCACCTC GGCTTCCCAA AGTGCTGGGA 45 TTACAGGCAT GAGCCACCAC GCCTGGCCCA GAGAGGGATG ATC'rAGAA GCTCGGGATT CTITCAAGCC C'ITTCCTCCT CTCTGAGCTT TCTACTCTCT GATGTCAAAG CATGGTTCCT GGCAGGACCA CCTCACCAGG CTCCCTCCCT CGCTCTCTCC GCAGTGCTCC TTCCAGGACC TGGACCTCTG CCCTCTGGAT GGCGGCATCC AGCTACGAAT CTCCGACCAC CACTACAGCA AGGGCTTCAG GCAGGCCGCG TCAGTTGTTG TGGCCATGGA CAAGCTGAGG AAGATGCTGG 'I1CCCTGCCC ACAGACCTrC CAGGAGAATG ACCTGAGCAC CYTCTYFCCC 50 TTCATCTJ17G AAGAAGGTAG TTAGCCAAGA GCAGGCAGTA GATCTCCACT TGTGTCCTCT TGGAAGTCAT CAAGCCCCAG CCAACTCAAT TCCCCCAGAG CCAAAGCCCT TTAAAGGTAG AAGGCCCAGC GGGGAGACAA AACAAAGAAG GCTGGAAACC AAAGCAATCA TCTCTITAGT GGAAACTATT C'ITAAAGAAG ATCTTGATGG CTACTGACAT TTGCAACTCC CTCACTC'TrT CTCAGGGGCC TrCACTTAC ATTGTCACCA GAGGTTCGTA ACCTCCCTGT GGGCTAGTGT TATGACCATC ACCATITTAC CTAAGTAGCT CTG'rrGCTCG GCCACAGTGA 55 GCAGTAATAG ACCTGAAGCT GGAACCCATG TCTAATAGTG TCAGGTCCAG TGTI1CTTAGC CACCCCACTC CCAGCTTCAT CCCTACTGGT GTTGTCATCA GAC2TrGACC GTATATGCTC AGGTGTCCTC CAAGAAATCA AATM~GCCA CCTCGCCTCA CGAGGCCTGC CCTTCTGA'rr TTATACCTAA ACAACATGTG CTCCACA TTT CAGAACCTAT CTTCTTICGAC ACATGGGATA ACGAGGCTTA TGTGCACGAT GCACCTGTAC GATCACTGAA CTGCACGCTC CGGGACTCAC AGCAAAAAAG CTTGGTGATG TCTGGTCCAT ATGAACTGAA AGCTCTCCAC 60 CTCCAGGGAC AGGATATGGA GCAACAAGGT AAATGGAAAC ATCCTGGT CCCTGCCTGG CCTCCTGGCA GCTTGCTAAT TCTCCATGTT TT'AAACAAAG TAGAAAGTTA A'r~rAAGGCA AATGATCAAC ACAAGTGAAA AAAAATATTA AAAAGGAATA TACAAACMT GGTCCTAGAA ATGGCACATT TGATTGCACT GGCCAGTGCA 'VrTG'AACA GGAGTGTGAC CCTGAGAAAT TAGACGGCTC AAGCACTCCC AGGACCATGT CCACCCAAGT CTCTTGGGCA TAGTGCAGTG TCAATTC117C CACAATATGG GGTCA'TrGA TGGACATGGC CTAACTGCCT 65 GTGGGTTCTC TCTCCTGTT GTTGAGGCTG AAACAAGAGT GCTGGAGCGA TAATGTGTCC ATCCCCCTCC CCAGTCTTCC CCCCTTGCCC CAACATCCGT CCCACCCAAT GCCAGGTGGT TCCTGTAGG GAAA TTTrAC WO 00/62736 PCT/USOO/08020 232 CGCCCAGCAG GAACTTATAT CTCTCCGCTG TAACGGGCAA AAGTTTCAAG TGCGGTGAAC CCATCA1TAG CTGTGGTGAT CTGCCTGGCA TCGTGCCACA GTAGCCAAAG CCTCTGCACA GGAGTGTGGG CAACTAAGGC TGCTGAC'ITT GAAGGACAGC CTCACTCAGG GGGAAGCTAT TrGCTCTCAG CCAGGCCAAG AAAATCCTGT T'rCTTTGGAA TCGGGTAGTA AGAGTGATCC CAGGGCCTCC AATTGACACT GCTGTGACTG AGGAAGATCA 5 AAATGAGTGT CTCTCTTTGG AGCCACTTTC CCAGCTCAGC CTCTCCTCTC CCAGTCTT CCCATGGGCT ACTCTCTGTr CCTGAAACAG TTCTGGTGCC TGATrTCTGG CAGAAGTACA GCTCACCTC lTCCTTTCC TTCCACATTG ATCAAGTI'GT TCCGCTCCTG TGGATGGGCA CATTGCCAGC CAGTGACACA ATGGCTTCCT TCCrrCCrrTC C=CAGCA'IT TAAAATGTAG ACCCTCTTTC ATTCTCCGTT CCTACTGCTA TGAGGCTCTG AGAAACCCTC AGGCCTITGA GGGGAAACCC TAAATCAACA AAATGACCCT GCTATTGTCT GTGAGAAGTC 10 AAG'ITATCCT GTGTCTrAciG CCAAGGAACC TCACTGTGGG TTCCCACAGA GGCTACCAAT TACATGTATC CTACTCTCGG GGCTAGGGGT TGGGGTGACC CTGCATGCTG TGTCCCTAAC CACAAGACCC CCTTC'IMCT TCAGTGGTGT TCTCCATGTC C TTGTACAA GGAGAAGAAA GTAATGACAA AATACCTGTG GCCTTGGGCC TCAAGGAAAA GAATCTGTAC CTGTCCTGCG TGTrGAAAGA TGATAAGCCC ACTCTACAGC TGGAGGTAAG TGAATGCTAT GGAATGAAGC CCTTCTCAGC CTCCTGCTAC CACTTN117CC CAGACAAYTC ACCTT1CTCCC 15 CGCCCCCATC CCTAGGAAAA GCTGGGAACA GGTCTATI'G ACAAG'TITG CA FTAATGTA AATAAATTTA ACATAATTFIT TAACTGCGTG CAACCTI'CAA TCCTGCTGCA GAAAATTAAA TCATI=GCC GATGTrATTA TGTCCTACCA TAG'I1ACAAC CCCAACAGAT TATATATTGT TAGGGCTGCT CTCA'ITTGAT AGACACCTTG GGAAATAGAT GACTTAAAGG GTCCCATTAT CACGTCCACT CCACTCCCAA AATCACCACC ACTATCACCT CCAGCTrCT CAGCAAAAGC TTCKITI'CCA AGTTGATGTC ATTCTAGGAC CATAAGGAAA AATACAATAA 20 AAAGCCCCTG GAAACTAGGT AcITcAAGAA GCTCTAGCTI' AAITPCACC CCCCCAAAAA AAAAAAA FTC TCACCTACAT TATGCTCCTC AGCATI1TGGC ACTAAGTI1 AGAAAAGAAG AAGGGCTCT[ TTFAATAATCA CACAGAAAGT TGGGGGCCCA GTTACAACTC AGGAGTCTGG CTCCTGATCA TGTGACCTGC TCGTCAG'l= CCMrCTGGC CAACCCAAAG AACATC ITTC CCATAGGCAT C'ITTGTCCCT TGCCCCACAA AAATTCT~rCT TTCTC'ITTCG CTciCAGAGTG TAGATCCCAA AAATTACCCA AAGAAGAAGA TGGAAAAGCG ATTTGTCTT1C 25 AACAAGATAG AAATCAATAA CAAGCTGGAA TTTGAGTCTG CCCAGTTCCC CAACTGGTAC ATCAGCACCT CTCAAGCAGA AAACATGCCC GTCTTCCTGG GAGGGACCAA AGGCGGCCAG GATATAACTG ACTTCACCAT GCAATfTGTG TCTITCCTAAA GAGAGCTGTA CCCAGAGAGT CCTGTGCTGA ATGTGGACTC AATCCCTAGG GCTGGCAGAA AGGGAACAGA AAGGTTTG AGTACGGCTA TAGCCTGGAC 1TTCCTGTTG TCTACACCAA TGCCCAACTG CCTGCCT7AG GGTAGTGCTA AdAGGATCTC CTGTCCATCA GCCAGGACAG TCAGCTCTCT 30 CC'ITTCAGGG CCAATCCCCA GCCCTITGT TGAGCCAGGC CTCTCTCACC TCTCCTACTC ACTTAAAGCC CGCCTGACAG AAACCACGGC CACATTTGGT TCTAAGAAAC CCTCTGTCAT TCGCTCCCAC ATTCTGATGA GCAACCGCTT CCCTA'1TTAT 'PTA ITTAT GTTGTTTGT ITGATTCAT TGGTCTAATT TATJ7CAAAGG GGGCAAGAAG TAGCAGTGTC TGTAAAAGAG CCTAG TT M AATAGCTATG GAATCAATTC ANITTTGGACT GGTGTGCTCT CMhAAATCA AGTCC'IMTAA TTAAGACTGA AAATATATAA GCTCAGATTA TTI7AAATGGG 35 AATATFI'ATA AATGAGCAAA TATCATACTG TTCAATGGTr CTGAAATAAA CTI'CACTGAA GAAAAAAAAA AAAGGGTCTC TCCTGATCAT TGACTGTCTG GATTGACACT GACAGTAAGC AAACAGGCTG TGAGAGTrCT TGGGACTAAG CCCACTCCTC A ITGCTGAGT GCTGCAAGTA CCTAGAAATA TCCTTrGGCCA CCGAAGACTA TCCTCCTCAC CCATCCCCTIT TATTTCGTTG TTCAACAGAA GGATATTCAG TGCACATCTG GAACAGGATC AGCTGAAGCA CTGCAGGGAG TCAGGACTGG TAGTAACAGC TACCATGATT TATCTATCAA TGCACCAAAC 40 ATCTGTTGAG CAAGCGCTAT GTACTAGGAG CTGGGAGTAC AGAGATGAGA ACAGTCACAA GTCCCTCCTC AGATAGGAGA GGCAGCTAGT TATAAGCAGA ACAAGGTAAC ATGACAAGTA GAGTAAGATA GAAGAACGAA GAGGAGTAGC CAGGAAGGAG GGAGGAGAAC GACATAAGAA TCAAGCCTAA AGGGATAAAC AGAAGATTTC CACACATGGG CTGGGCCAAT TGGGTGTCGG TTACGCCTGT AATCCCAGCA C'TTTGGGTGG CAGGGGCAGA AAGATCGCTT GAGCCCAGGA G'TFCAAGACC AGCCTGGGCA ACATAGTGAG ACTCCCATCT CTACAAAAAA 45 TAAATAAATA AATAAAACAA TCAGCCAGGC ATGCTGGCAT GCACCTGTAG TCCTAGCTAC TTGGGAAGCT GACACTGGAG GATTGCTTGA GCCCAGAAGT TCAAGACTGC AGTGAG=rA TCCGTTGACC TGCAGGTCGA C 3' (FRAG. NO: )(SEQ. ED NO:2512) 5'-ACAAACC'TrT TCGAGGCAAA AGGCAAAAAA GGCTGCTCTG GGA'ITCTCTT CAGCCAATCT TCAATGCTCA AGTGTCTGAA GCAGCCATGG CAGAAGTACC TAAGCTCGCC AGTGAAATGA TGGCT7A1TA CAGTGGCAAT 50 GAGGATGACT TGTTC1TTGA AGCTGATGGC CCTAAACAGA TGAAGTGCTC CT7CCAGGAC CTGGACCTCT GCCCTCTGGA TGGCGGCATC CAGCTACGAA TCTCCGACCA CCACTACAGC AAGGGC'ITCA GGCAGGCCGC GTCAGTTGTT GTGGCCATGG ACAAGCTGAG GAAGATGCTG GTFCCCTGCC CACAGACCTT CCAGGAGAAT GACCTGAGCA CCTTCTTTCC CTrCATCMP GAAGAAGAAC CTATCTTCTr CGACACATGG GATAACGAGG CTTATGTGCA CGATGCACCT GTACGATCAC TGAACTGCAC GCTCCGGGAC TCACAGCAAA AAAGCTITGGT 55 GATGTCTGGT CCATATGAAC TGAAAGCTCT CCACCTCCAG GGACAGGATA TGGAGCAACA AGTGGTGTTC TCCATGTCCT 'FrGTACAAGG AGAAGAAAGT AATGACAAAA TACCTGTGGC CT~rGGGCCTC AAGGAAAAGA ATCTGTACCT GTCCTGCGTG TTGAAAGATG ATAAGCCCAC TCTACAGCTG GAGAGTGTAG ATCCCAAAAA TITACCCAAAG AAGAAGATGG AAAAGCGAT[ TGTC'rCAAC AAGATAGAAA TCAATAACAA GCTGGAAYT GAGTCTGCCC AGTTCCCCAA CTGGTACATC AGCACCTCTC AAGCAGAAAA CATGCCCGTC TTCCTGGGAG 60 GGACCAAAGG CGGCCAGGAT ATAACTGACT TCACCATGCA A'IMFGTGTCT TCCTAAAGAG AGCTGTACCC AGAGAGTCCT GTGCTGAATG TGGACTCAAT CCCTAGGGCT GGCAGAAAGG GAACAGAAAG G'T=~GAGT ACGGCTATAG CCTGGACTTT CCTGTTGTCT ACACCAATGC CCAACTGCCT GCCTrAGGGT AGTGCTAAGA GGATCTCCTG TCCATCAGCC AGGACAGTCA GCTCTCTCCT TrCAGGGCCA ATCCCAGCCC 1TTGTTGAG CCAGGCCTCT CTCACCTCTC CTACTCACYJ7 AAAGCCCGCC TGACAGAAAC CAGGCCACAT 1TTGGT-rCTA 65 AGAAACCCTC CTCTGTCATT CGCTCCCACA TTCTGATGAG CAACCGCTTC CCTATI'TATT TNITTKITTTG TTTGTTTGTT TTGATTCATTr GGTCTAAMTT ATTCAAAGGG GGCAAGAAGT AGCAGTGTCT GTAAAAGAGC WO 00/62736 PCT/USOO/08020 233 CTAGTTTA ATAGCTATGG AATCAATTCA ATTTGGACTG GTGTGCTCTC TTAAATCAA GTCCTTTAAT TAAGACTGAA AATATATAAG CTCAGATTAT TTAAATGGGA ATATTTATAA ATGAGCAAAT ATCATACTGT TCAATGGTTC TCAAATAAAC TTCACT-3' (FRAG. NO:_)(SEQ. ID NO:2513) 5'-CTGGCAGGAG TAGCAGCTGC CCCTTGGCGC GACTGCTGGA GCCGCGAACT AGAGAAACAC AGACACGCCT 5 CATAGAGCAA CGGCGTCTCT CGGAGCGTGG AGCCCGCCAA GCTCGAGCTG AGCTTTCGCT TGCCGTCCAC CACTGCCCAC ACTGTCGTT GCTGCCATCG CAGACCTGCT GCTGACTTCC ATCCCTCTGG ATCCGGCAAG GGCCTGCGAT TTTGACAATG TCAAGATTTA CCGTATATCC CTGTTTGTTT GGATACACCA GTGACGTCCA CTTCTAGAAG ACAAAGTTAT ATTACTTAAA CAACCAAAGA TATGAAACTA TCCATGAAGA ACAATATTAT CAATACACAG CAGTCTTTTG TAACCATGCC CAATGTGATT GTACCAGATA TTGAAAAGGA AATACGAAGG 10 ATGGAAAATG GAGCATGCAG CTCCTITCT GAGGATGATG ACAGTGCCTC TACATCTGAA GAATCAGAGA ATGAAAACCC TCATGCAAGG GGTrCCTTTA GTTATAAGTC ACTCAGAAAG GGAGGACCAT CACAGAGGGA GCAGTACCTG CCTGGTGCCA TTGCCATTT TAATGTGAAC AACAGCGACA ATAAGGACCA GGAACCAGAA GAAAAAAAGA AAAAGAAAAA AGAAAAGAAG AGCAAGTCAG ATGATAAAAA CGAAAATAAA AACGACCCAA AGAAGAAGAT GGAAAAGCGA-3' (FRAG. NO:_)(SEQ. ID NO:2514) 15 5'-ATGGCCAAAG TTCCAGACAT GTTTGAAGAC CTGAAGAACT GTTACAGTGA AAATGAAGAA GACAGTTCCT CCATTGATCA TCTGTCTCTG AATCAGAAAT CCTTCTATCA TGTAAGCTAT GGCCCACTCC ATGAAGGCTG CATGGATCAA TCTGTGTCTC TGAGTATCTC TGAAACCTCT AAAACATCCA AGCTTACCTT CAAGGAGAGC ATGGTGGTAG TAGCAACCAA CGGGAAGGTT CTGAAGAAGA GACGGTTGAG TTTAAGCCAA TCCATCACTG ATGATGACCT GGAGGCCATC GCCAATGACT CAGAGGAAGA AATCATCAAG CCTAGGTCAG CACCTTTTAG 20 CTTCCTGAGC AATGTGAAAT ACAACTTTAT GAGGATCATC AAATACGAAT TCATCCTGAA TGACGCCCTC AATCAAAGTA TAATTCGAGC CAATGATCAG TACCTCACGG CTGCTGCATr ACATAATCTG GATGAAGCAG TGAAATTTGA CATGGGTGCT TATAAGTCAT CAAAGGATGA TGCTAAAATT ACCGTGATTC TAAGAATCTC AAAAACTCAA TTGTATGTGA CTGCCCAAGA TGAAGACCAA CCAGTGCTGC TGAAGGAGAT GCCTGAGATA CCCAAAACCA TCACAGGTAG TGAGACCAAC CTCCTCTTCT TCTGGGAAAC TCACGGCACT AAGAACTATT 25 TCACATCAGT TGCCCATCCA AACTTGTfA TTGCCACAAA GCAAGACTAC TGGGTGTGCT TGGCAGGGGG GCCACCCTCT ATCACTGACT TTCAGATACT GGAAAACCAG GCGTAGGTCT GGAGTCTCAC TTGTCTCACT TGTGCAGTGT TGACAGTTCA TATGTACCAT GTACATGAAG AAGCTAAATC CTTTACTGTT AGTCATTTGC TGAGCATGTA CTGAGCCTTG TAATTCTAAA TGAATGTTA CACTC'TGT AAGAGTGGAA CCAACACTAA CATATAATGT TGTTATTTAA AGAACACCCT ATATTGCA TAGTACCAAT CATTTTAATT ATTATTCTTC 30 ATAACAATTT TAGGAGGACC AGAGCTACTG ACTATGGCTA CCAAAAAGAC TCTACCCATA TTACAGATGG GCAAATTAAG GCATAAGAAA ACTAAGAAAT ATGCACAATA GCAGTTGAAA CAAGAAGCCA CAGACCTAGG ATTTCATGAT TTCATTTCAA CTGTTTGCCT TCTGCTITA AGTTGCTGAT GAACTCTTAA TCAAATAGCA TAAGTTTCTG GGACCTCAGT TTTATCATTT TCAAAATGGA GGGAATAATA CCTAAGCCTT CCTGCCGCAA CAGTTTA TGCTAATCAG GGAGGTCATT TTGGTAAAAT ACTTCTCGAA GCCGAGCCTC AAGATGAAGG 35 CAAAGCACGA AATGTTATTT TAATTATT ATTrATATAT GTATTTATAA ATATATTTAA GATAATTATA ATATACTATA TATGGGAA CCCCTTCATC CTCTGAGTGT GACCAGGCAT CCTCCACAAT AGCAGACAGT GTTTTCTGGG ATAAGTAAGT TTGATTTCAT TAATACAGGG CATITTGGTC CAAGTTGTGC TTATCCCATA GCCAGGAAAC TCTGCATTCT AGTACTTGGG AGACCTGTAA TCATATAATA AATGTACATT AATTACCTTG AGCCAGTAAT TGGTCCGATC TTTGACTCTT TTGCCATTAA ACTTACCTGG GCATTCTTGT TTCATTCAAT 40 TCCACCTGCA ATCAAGTCCT ACAAGCTAAA ATTAGATGAA CTCAACTTTG ACAACCATAG ACCACTGTTA TCAAAACTTT CTTCTGGA ATGTAATCAA TGTTTCTTCT AGGTTCTAAA AATTGTGATC AGACCATAAT GTTACATTAT TATCAACAAT AGTGATTGAT AGAGTGTTAT CAGTCATAAC TAAATAAAGC TTGCAAGTGA GGGAGTCATT TCATTGGCGT TTGAGTCAGC AAAGAAGTCA AG-3' (FRAG. NO:_)(SEQ. ID NO:2515) 5'-AGCTGCCAGC CAGAGAGGGA GTCATTTCAT TGGCGTTTGA GTCAGCAAAG AAGTCAAGAT GGCCAAAGTT 45 CCAGACATGT TTGAAGACCT GAAGAACTGT TACAGTGAAA ATGAAGAAGA CAGTTCCTCC ATTGATCATC TGTCTCTGAA TCAGAAATCC TTCTATCATG TAAGCTATGG CCCACTCCAT GAAGGCTGCA TGGATCAATC TGTGTCTCTG AGTATCTCTG AAACCTCTAA AACATCCAAG CTTACCTTCA AGGAGAGCAT GGTGGTAGTA GCAACCAACG GGAAGGTTCT GAAGAAGAGA CGGTTGAGTr TAAGCCAATC CATCACTGAT GATGACCTGG AGGCCATCGC CAATGACTCA GAGGAAGAAA TCATCAAGCC TAGGTCATCA CCTTTAGCT TCCTGAGCAA 50 TGTGAAATAC AACTTTATGA GGATCATCAA ATACGAATTC ATCCTGAATG ACGCCCTCAA TCAAAGTATA ATTCGAGCCA ATGATCAGTA CCTCACGGCT GCTGCATTAC ATAATCTGGA TGAAGCAGTG AAATTTGACA TGGGTGCTTA TAAGTCATCA AAGGATGATG CTAAAATTAC CGTGATTCTA AGAATCTCAA AAACTCAATT GTATGTGACT GCCCAAGATG AAGACCAACC AGTGCTGCTG AAGGAGATGC CTGAGATACC CAAAACCATC ACAGGTAGTG AGACCAACCT CCTCTTCTTC TGGGAAACTC ACGGCACTAA GAACTATTTC ACATCAGTTG 55 CCCATCCAAA CTTGTTTATr GCCACAAAGC AAGACTACTG GGTGTGCTTG GCAGGGGGGC CACCCTCTAT CACTGACTTT CAGATACTGG AAAACCAGGC GTAGGTCTGG AGTCTCACTT GTCTCACTTG TGCAGTGTTG ACAGTTCATA TGTACCATGT ACATGAAGAA GCTAAATCCT TTACTGTTAG TCATTTGCTG AGCATGTACT GAGCCTTGTA ATTCTAAATG AATGTTTACA CTCTTrGTAA GAGTGGAACC AACACTAACA TATAATGTTG WO 00/62736 PCT/USOO/08020 234 TTATTTAAAG AACACCCTAT ATTGCATA GTACCAATCA TTTAATTAT TATTCTTCAT AACAATTTTA GGAGGACCAG AGCTACTGAC TATGGCTACC AAAAAGACTC TACCCATATT ACAGATGGGC AAATTAAGGC ATAAGAAAAC TAAGAAATAT GCACAATAGC AGTCGAAACA AGAAGCCACA GACCTAGGAT TTCATGATTT CATTTCAACT GTGCCTTC TGCTTTTAAG TTGCTGATGA ACTCTTAATC AAATAGCATA AGTTTCTGGG 5 ACCTCAGTTT TATCATTTC AAAATGGAGG GAATAATACC TAAGCCTTCC TGCCGCAACA GTTTTATG CTAATCAGGG AGGTCATT GGTAAAATAC TTCTCGAAGC CGAGCCTCAA GATGAAGGCA AAGCACGAAA TGTTATTT TAATTATTAT TTATATATGT ATTTATAAAT ATATTTAAGA TAATTATAAT ATACTATATT TATGGGAACC CCTTCATCCT CTGAGTGTGA CCAGGCATCC TCCACAATAG CAGACAGTGT TTTCTGGGAT AAGTAAGTTT GATTTCATTA ATACAGGGCA TTTGGTCCA AGTTGTGCTT ATCCCATAGC CAGGAAACTC 10 TGCATTCTAG TACTTGGGAG ACCTGTAATC ATATAATAAA TGTACATTAA TTACCTTGAG CCAGTAATTG GTCCGATCTT TGACTCTTTT GCCATTAAAC TTACCTGGGC ATTCTTGTTT CATrCAAITTC CACCTGCAAT CAAGTCCTAC AAGCTAAAAT TAGATGAACT CAACTTTGAC AACCATGAGA CCACTGTTAT CAAAACTTTC TTTCTGGAA TGTAATCAAT GTTrCTrCTA GGTTCTAAAA ATTGTGATCA GACCATAATG TTACATTATT ATCAACAATA GTGATTGATA GAGTGTTATC AGTCATAACT AAATAAAGCT TGCAACAAAA TTCTCTG-3' 15 (FRAG. NO:_)(SEQ. ID NO:2516) Human Interleukin-1 Receptor (IL-1 R) Nucleic Acids and Anti-sense Oligonucleotide Fragments 5'-GCCACGTGCT GCTGGGTCTC AGTCCTCCAC TTCCCGTGTC CTCTGGAAGT TGTCAGGAGC AATGTTGCGC TTGTACGTGT TGGTAATGGG AGTTTCTGCC TTCACCCTTC AGCCTGCGGC ACACACAGGG GCTGCCAGAA GCTGCCGGTT TCGTGGGAGG CATTACAAGC GGGAGTTCAG GCTGGAAGGG GAGCCTGTAG CCCTGAGGTG 20 CCCCCAGGTG CCCTACTGGT TGTGGGCCTC TGTCAGCCCC CGCATCAACC TGACATGGCA TAAAAATGAC TCTGCTAGGA CGGTCCCAGG AGAAGAAGAG ACACGGATGT GGGCCCAGGA CGGTGCTCTG TGGCTTCTGC CAGCCTTGCA GGAGGACTCT GGCACCTACG TCTGCACTAC TAGAAATGCT TCTTACTGTG ACAAAATGTC CATTGAGCTC AGAGTTTTTG AGAATACAGA TGCTTTCCTG CCGTTCATCT CATACCCGCA AATTTTAACC TTGTCAACCT CTGGGGTATT AGTATGCCCT GACCTGAGTG AATTCACCCG TGACAAAACT GACGTGAAGA 25 TTCAATGGTA CAAGGATTCT CTTCTTGG ATAAAGACAA TGAGAAATTT CTAAGTGTGA GGGGGACCAC TCACTTACTC GTACACGATG TGGCCCTGGA AGATGCTGGC TATrACCGCT GTGTCCTGAC ATTTGCCCAT GAAGGCCAGC AATACAACAT CACTAGGAGT ATTGAGCTAC GCATCAAGAA AAAAAAAGAA GAGACCATTC CTGTGATCAT TTCCCCCCTC AAGACCATAT CAGCTTCTCT GGGGTCAAGA CTGACAATCC CGTGTAAGGT GTTTCTGGGA ACCGGCACAC CCTTAACCAC CATGCTGTGG TGGACGGCCA ATGACACCCA CATAGAGAGC 30 GCCTACCCGG GAGGCCGCGT GACCGAGGGG CCACGCCAGG AATATTCAGA AAATAATGAG AACTACATTG AAGTGCCATT GATTTTTGAT CCTGTCACAA GAGAGGATTT GCACATGGAT TTTAAATGTG TTGTCCATAA TACCCTGAGT TTTCAGACAC TACGCACCAC AGTCAAGGAA GCCTCCTCCA CGTTCTCCTG GGGCATTGTG CTGGCCCCAC TCACTGGC CTTCTTGGTT TTGGGGGGAA TATGGATGCA CAGACGGTGC AAACACAGAA CTGGAAAAGC AGATGGTCTG ACTGTGCTAT GGCCTCATCA TCAAGACTTT CAATCCTATC CCAAGTGAAA 35 TAAATGGAAT GAAATAATTC AAACACAAAA AAAAAAAAAA AAAAAAAA GCCGGAGCCG ACTCGGAGCG CGCGGCGCGG CCGGGAGGAG CCGAGCGCGC CGGGCGCGGC GTGGGGGCGC CGGCTGCCCC GCGCGCCCAG GGAGCGGCAG GAATGTGACA ATCGCGCGCC CGCACCGTAG CACTCCTCGC TCGGCTCCTA GGGCTCTCGC CCTCTGAGCT GAGCCGGGTT CCGCCCGGGC TGGGATCCCA TCACCCTCCA CGGCCGTCCG TCCAGGTAGA CGCACCCTCT GAAGATGGTG ACTCCCTCCT GAGAAGCTGG ACCCCTTGGT AAAAGACAAG GCCTTCTCCA 40 AGAAGAATAT GAAAGTGTTA CTCAGACTTA TTTGTTTCAT AGCTCTACTG ATTTCTTCTC TGGAGGCTGA TAAATGCAAG GAACGTGAAG AAAAAATAAT TAGTGTCA TCTGCAAATG AAATTGATGT TCGTCCCTGT CCTCTTAACC CAAATGAACA CAAAGGCACT ATAACTTGGT ATAAAGATGA CAGCAAGACA CCTGTATCTA CAGAACAAGC CTCCAGGATT CATCAACACA AAGAGAAACT TTGGTTTGTT CCTGCTAAGG TGGAGGATTC AGGACATTAC TATTGCGTGG TAAGAAATTC ATCTTACTGC CTCAGAATTA AAATAAGTGC AAAATTGTG 45 GAGAATGAGC CTAACTTATG TTATAATGCA CAAGCCATAT TTAAGCAGAA ACTACCCGTT GCAGGAGACG GAGGACTTGT GTGCCCTTAT ATGGAGTTTT TTAAAAATGA AAATAATGAG TTACCTAAAT TACAGTGGTA TAAGGATTGC AAACCTCTAC TTCTTGACAA TATACACTTT AGTGGAGTCA AAGATAGGCT CATCGTGATG AATGTGGCTG AAAAGCATAG AGGGAACTAT ACTTGTCATG CATCCTACAC ATACTTGGGC AAGCAATATC CTATTACCCG GGTAATAGAA TTTATTACTC TAGAGGAAAA CAAACCCACA AGGCCTGTGA TTGTGAGCCC 50 AGCTAATGAG ACAATGGAAG TAGACTTGGG ATCCCAGATA CAATTGATCT GTAATGTCAC CGGCCAGTTG AGTGACATTG CTTACTGGAA GTGGAATGGG TCAGTAATTG ATGAAGATGA CCCAGTGCTA GGGGAAGACT ATTACAGTGT GGAAAATCCT GCAAACAAAA GAAGGAGTAC CCTCATCACA GTGCTTAATA TATCGGAAAT TGAAAGTAGA TTTTATAAAC ATCCATAC CTGTTGCC AAGAATACAC ATGGTATAGA TGCAGCATAT ATCCAGTTAA TATATCCAGT CACTAATTTC CAGAAGCACA TGATTGGTAT ATGTGTCACG TTGACAGTCA 55 TAATTGTGTG T7CTGTTTC ATCTATAAAA TCTTCAAGAT TGACATTGTG CTTTGGTACA GGGATITCCTG CTATGATTTT CTCCCAATAA AAGCTTCAGA TGGAAAGACC TATGACGCAT ATATACTGTA TCCAAAGACT GTTGGGGAAG GGTCTACCTC TGACTGTGAT ATTGTGT TTAAAGTCTT GCCTGAGGTC TTGGAAAAAC AGTGTGGATA TAAGCTGTTC ATTTATGGAA GGGATGACTA CGTTGGGGAA GACATTGTTG AGGTCATTAA TGAAAACGTA AAGAAAAGCA GAAGACTGAT TATCATTTTA GTCAGAGAAA CATCAGGCTT CAGCTGGCTG 60 GGTGGTTCAT CTGAAGAGCA AATAGCCATG TATAATGCTC TTGTTCAGGA TGGAATTAAA GTTGTCCTGC TTGAGCTGGA GAAAATCCAA GACTATGAGA AAATGCCAGA ATCGATTAAA TTCATTAAGC AGAAACATGG GGCTATCCGC TGGTCAGGGG ACTITACACA GGGACCACAG TCTGCAAAGA CAAGGTTCTG GAAGAATGTC AGGTACCACA TGCCAGTCCA GCGACGGTCA CCTTCATCTA AACACCAGTT ACTGTCACCA GCCACTAAGG WO 00/62736 PCT/USOO/08020 235 AGAAACTGCA AAGAGAGGCT CACGTGCCTC TCGGGTAGCA TGGAGAAGTT GCCAAGAGTT CTTTAGGTGC CTCCTGTCTT ATGGCGTTGC AGGCCAGGTT ATGCCTCATG CTGACTTGCA GAGTTCATGG AATGTAACTA TATCATCCTT TATCCCTGAG GTCACCAGGA ATCAGG-3' (FRAG NO:_)(SEQ. ID NO:2520) 5'-GCCACGTGCT GCTGGGTCTC AGTCCTCCAC TTCCCGTGTC CTCTGGAAGT TGTCAGGAGC AATGTTGCGC 5 TTGTACGTGT TGGTAATGGG AGTTTCTGCC TTCACCCTTC AGCCTGCGGC ACACACAGGG GCTGCCAGAA GCTGCCGGTT TCGTGGGAGG CATTACAAGC GGGAGTTCAG GCTGGAAGGG GAGCCTGTAG CCCTGAGGTG CCCCCAGGTG CCCTACTGGT TGTGGGCCTC TGTCAGCCCC CGCATCAACC TGACATGGCA TAAAAATGAC TCTGCTAGGA CGGTCCCAGG AGAAGAAGAG ACACGGATGT GGGCCCAGGA CGGTGCTCTG TGGCTTCTGC CAGCCTTGCA GGAGGACTCT GGCACCTACG TCTGCACTAC TAGAAATGCT TCTTACTGTG ACAAAATGTC 10 CATTGAGCTC AGAGTTTTTG AGAATACAGA TGCTCCTG CCGTTCATCT CATACCCGCA AATTTTAACC TTGTCAACCT CTGGGGTATT AGTATGCCCT GACCTGAGTG AATTCACCCG TGACAAAACT GACGTGAAGA TTCAATGGTA CAAGGATTCT CTTCTITTGG ATAAAGACAA TGAGAAATTT CTAAGTGTGA GGGGGACCAC TCACTTACTC GTACACGATG TGGCCCTGGA AGATGCTGGC TATTACCGCT GTGTCCTGAC ATTTGCCCAT GAAGGCCAGC AATACAACAT CACTAGGAGT ATTGAGCTAC GCATCAAGAA AAAAAAAGAA GAGACCATTC 15 CTGTGATCAT TTCCCCCCTC AAGACCATAT CAGCTTCTCT GGGGTCAAGA CTGACAATCC CGTGTAAGGT GTTrCTGGGA ACCGGCACAC CCTTAACCAC CATGCTGTGG TGGACGGCCA ATGACACCCA CATAGAGAGC GCCTACCCGG GAGGCCGCGT GACCGAGGGG CCACGCCAGG AATATTCAGA AAATAATGAG AACTACATTG AAGTGCCATT GATTTGAT CCTGTCACAA GAGAGGATTT GCACATGGAT TTTAAATGTG TTGTCCATAA TACCCTGAGT TTTCAGACAC TACGCACCAC AGTCAAGGAA GCCTCCTCCA CGTTCTCCTG GGGCATTGTG 20 CTGGCCCCAC TTTCACTGGC CTTCTTGGTT TTGGGGGGAA TATGGATGCA CAGACGGTGC AAACACAGAA CTGGAAAAGC AGATGGTCTG ACTGTGCTAT GGCCTCATCA TCAAGACTTT CAATCCTATC CCAAGTGAAA TAAATGGAAT GAAATAATTC AAACACAAAA AAAAAAAAAA AAAAAAAA-3' (FRAG. NO:_)(SEQ. ID NO:2518) 5'-GCCGGAGCCG ACTCGGAGCG CGCGGCGCGG CCGGGAGGAG CCGAGCGCGC CGGGCGCGGC 25 GTGGGGGCGC CGGCTGCCCC GCGCGCCCAG GGAGCGGCAG GAATGTGACA ATCGCGCGCC CGCACCGTAG CACTCCTCGC TCGGCTCCTA GGGCTCTCGC CCTCTGAGCT GAGCCGGGTT CCGCCCGGGC TGGGATCCCA TCACCCTCCA CGGCCGTCCG TCCAGGTAGA CGCACCCTCT GAAGATGGTG ACTCCCTCCT GAGAAGCTGG ACCCCTTGGT AAAAGACAAG GCCTTCTCCA AGAAGAATAT GAAAGTGTTA CTCAGACTTA TITGTTTCAT AGCTCTACTG ATTTCTTCTC TGGAGGCTGA TAAATGCAAG GAACGTGAAG AAAAAATAAT TTTAGTGTCA 30 TCTGCAAATG AAATTGATGT TCGTCCCTGT CCTCTTAACC CAAATGAACA CAAAGGCACT ATAACTTGGT ATAAAGATGA CAGCAAGACA CCTGTATCTA CAGAACAAGC CTCCAGGATT CATCAACACA AAGAGAAACT TTGGTTT7GTT CCTGCTAAGG TGGAGGATTC AGGACATTAC TATTGCGTGG TAAGAAATTC ATCTTACTGC CTCAGAATTA AAATAAGTGC AAAATTGTG GAGAATGAGC CTAACTTATG TTATAATGCA CAAGCCATAT TTAAGCAGAA ACTACCCGTT GCAGGAGACG GAGGACTTGT GTGCCCTAT ATGGAGTT TTAAAAATGA 35 AAATAATGAG TTACCTAAAT TACAGTGGTA TAAGGATTGC AAACCTCTAC TTCTTGACAA TATACACTTT AGTGGAGTCA AAGATAGGCT CATCGTGATG AATGTGGCTG AAAAGCATAG AGGGAACTAT ACTTGTCATG CATCCTACAC ATACTTGGGC AAGCAATATC CTATTACCCG GGTAATAGAA TTTATTACTC TAGAGGAAAA CAAACCCACA AGGCCTGTGA TTGTGAGCCC AGCTAATGAG ACAATGGAAG TAGACTTGGG ATCCCAGATA CAATTGATCT GTAATGTCAC CGGCCAGTTG AGTGACATTG CTTACTGGAA GTGGAATGGG TCAGTAATTG 40 ATGAAGATGA CCCAGTGCTA GGGGAAGACT ATTACAGTGT GGAAAATCCT GCAAACAAAA GAAGGAGTAC CCTCATCACA GTGCTTAATA TATCGGAAAT TGAAAGTAGA TTTTATAAAC ATCCATTTAC CTGTTTTGCC AAGAATACAC ATGGTATAGA TGCAGCATAT ATCCAGTTAA TATATCCAGT CACTAATTTC CAGAAGCACA TGATTGGTAT ATGTGTCACG TTGACAGTCA TAATTGTGTG TTCTGTTC ATCTATAAAA TCTTCAAGAT TGACATTGTG CTGGTACA GGGATTCCTG CTATGATT CTCCCAATAA AAGCTTCAGA TGGAAAGACC 45 TATGACGCAT ATATACTGTA TCCAAAGACT GTTGGGGAAG GGTCTACCTC TGACTGTGAT ATTTGTGT TTAAAGTC'TT GCCTGAGGTC TTGGAAAAAC AGTGTGGATA TAAGCTGTTC ATTTATGGAA GGGATGACTA CGTTGGGGAA GACATTGTTG AGGTCATTAA TGAAAACGTA AAGAAAAGCA GAAGACTGAT TATCATTTTA GTCAGAGAAA CATCAGGCTT CAGCTGGCTG GGTGGTTCAT CTGAAGAGCA AATAGCCATG TATAATGCTC TTGTTCAGGA TGGAATTAAA GTTGTCCTGC TTGAGCTGGA GAAAATCCAA GACTATGAGA AAATGCCAGA 50 ATCGATTAAA TTCATTAAGC AGAAACATGG GGCTATCCGC TGGTCAGGGG ACTTTACACA GGGACCACAG TCTGCAAAGA CAAGGTTCTG GAAGAATGTC AGGTACCACA TGCCAGTCCA GCGACGGTCA CCTTCATCTA AACACCAGTT ACTGTCACCA GCCACTAAGG AGAAACTGCA AAGAGAGGCT CACGTGCCTC TCGGGTAGCA TGGAGAAGTT GCCAAGAGTT CTTTAGGTGC CTCCTGTCTT ATGGCGTTGC AGGCCAGGTT ATGCCTCATG CTGACTTGCA GAGTrCATGG AATGTAACTA TATCATCCTT TATCCCTGAG GTCACCAGGA ATCAGG-3' 55 (FRAG. NO:_)(SEQ. ID NO:2519) Human Interleukin-8* Fragments Antisense Oligonucleotide Fragments 5'-GBTGTTTGTT' BCCBBBGCBT CBBGBBTBGC TTTGCTBTCT BBGGBTCBCB TTBGBCBTB GGBBBBCGCT GTBGGTCBGBB BGBTGTGCTF BCCTTCBCBC BGBGCTGCBG BBBTCBGGBBGG CTGCCBBGBGBG CCBCGGCCBGC TTGGBGTCBT GTTTBCBCBC BGTGBGGTGC TCCGGTGGCT TTTTGCTTGT GTGCTCTGCT 60 GTCTCTG TTC CTTCCGGTGG TTTCTTCCTG GCTCTTGTCC TTTCTCTTGG CCCTTGGCCC-3' (FRAG. NO:1834) (SEQ. ID NO:1847) 5'-G CTC CGG-3' (FRAG. NO:1835) (SEQ. ID NO:1848) 5'-CBBGBBTBGC-3' (FRAG. NO:1836) (SEQ. ID NO:1849) 5'-CBCBC BGTGBGGTGC-3' (FRAG. NO:1837) (SEQ. ID NO:1850) 65 5'-BCCBBBGCBT CBBGBBTBGC-3' (FRAG. NO:1838) (SEQ. ID NO:1851) WO 00/62736 PCT/USOO/08020 236 5'-GCCBBGBGBG CCBCGGCCBGC-3' (FRAG. NO:1839) (SEQ. ID NO:1852) 5'-GTG CTC CGG TGG CTT TTT-3' (FRAG. NO:1289)(SEQ. ID NO:1298) 5'-GCT TGT GTG CTC TGC TGT CTC TG-3' (FRAG. NO:1290)(SEQ. ID NO:1299) 5'-'TTC CTT CCG GTG GTT TCT TCC TGG CTC TTG TCC T-3' (FRAG. NO:1291)(SEQ. ID NO:1300) 5 5'-TTC TCT TGG CCC TTG GCC C-3' (FRAG. NO:1292)(SEQ. ID NO:1301) 5'-GBTGTTTGTT BCCBBBGCBT CBBGBBTBGC TGCTBTCT BBGGBTCBCB TTTBGBCBTB GGBBBBCGCT GTBGGTCBGBB BGBTGTGCTT BCCTTCBCBC BGBGCTGCBG BBBTCBGGBBGG CTGCCBBGBGBG CCBCGGCCBGC TrGGBGTCBT GTTTBCBCBC BGTGBGGTGC TCCGGTGGCT TTTGCTTGT-3' (FRAG. NO:1840) (SEQ. ID NO:1853) 10 Human IL-8 Receptor Alpha Antisense Oligonucleotide Fragments 5'-ACAGGGGCTG TAATCTTCATC TGCAGGTGGC ATGCCAGTGA AATAGATC ATCAAAATCC CACATCTGTG GATCTGTAAT ATTTGACATG TCCTCTTCAG TTTCAGCAAT GGTTTGATCT AACTGAAGCA CCGGCCAGGB CBGGGGCTGT BBTCTTCBTC TGCBGGTGGC BTGCCBGTGB BBTTTBGBTC BTCBBBBTCC CBCBTCTGTG GBTCTGTBBT BTTTGBCBTG TCCTCTTCBG TTTCBGCBB TGGTTTGBTC TBBCTGBBGC BCCGGCCBGG 15 TGGCTCGGTG CTTCTGCCCC TGTTGTTGCG GCGCTCGGTT GGTGTGGCCC CTGTGGTGCT TCGTTTCCCC CTCTTTCTCT TTGTTCGGGG GTTCTTGTGG CGGGCTGCTT GTCTCGTTCC-3'(FRAG.NO:1841)(SEQ. ID NO:1854) 5'-CBGGGGC-3' (FRAG. NO:1842) (SEQ. ID NO:1855) 5'-GCBGGTGGC-3' (FRAG. NO:1843) (SEQ. ID NO:1856) 5'-GCGGCGCTC-3' (FRAG. NO:1844) (SEQ. ID NO:1857) 20 5'-TGGCTCGGTGCTTrCTGCCCC (FRAG. NO:1293)(SEQ. ID NO:1302) 5'-TGTTGTTGCGGCGCTC (FRAG. NO:1294)(SEQ. ID NO:1303) 5'-GGTTGGTGTGGCCCCTG (FRAG. NO:1295)(SEQ. ID NO:1304) 5'-TGGTGCTTCGTTTCC (FRAG. NO:1296)(SEQ. ID NO:1305) 5'-CCCTCTTTCTCTTTGTTC (FRAG. NO:1297)(SEQ. ID NO:1306) 25 5'-GGGGGTTCTTGTGGC (FRAG. NO:1298)(SEQ. ID NO:1307) 5'-GGGCTGCTTGTCTCGTTCC (FRAG. NO:1299)(SEQ. ID NO:1308) 5'-ACAGGGGCTG TAATCTTCATC TGCAGGTGGC ATGCCAGTGA AATTAGATC ATCAAAATCC CACATCTGTG GATCTGTAAT ATTTGACATG TCCTCTTCAG TTTCAGCAAT GGTTTGATCT AACTGAAGCA CCGGCCAGG-3' (FRAG. NO:1845) (SEQ. ID NO:1858) 30 5'-B CBGGGGCTGT BBTCTTCBTC TGCBGGTGGC BTGCCBGTGB BBTTTBGBTC BTCBBBBTCC CBCBTCTGTG GBTCTGTBBT BTTGBCBTG TCCTCTTCBG TTrCBGCBB TGGTTTGBTC TBBCTGBBGC BCCGGCCBGG-3' (FRAG. NO:1846) (SEQ. ID NO:1859) Interleukin-11 (IL-11) Nucleic Acid and Antisnese Oligonucleotide Fragments 5'-GCTCAGGGCA CATGCCTCCC CTCCCCAGGC CGCGGCCCAG CTGACCCTCG GGGCTCCCCC GGCAGCGGAC 35 AGGGAAGGGT TAAAGGCCCC CGGCTCCCTG CCCCCTGCCC TGGGGAACCC CTGGCCCTGT GGGGACATGA ACTGTGTG CCGCCTGGTC CTGGTCGTGC TGAGCCTGTG GCCAGATACA GCTGTCGCCC CTGGGCCACC ACCTGGCCCC CCTCGAGTTT CCCCAGACCC TCGGGCCGAG CTGGACAGCA CCGTGCTCCT GACCCGCTCT CTCCTGGCGG ACACGCGGCA GCTGGCTGCA CAGCTGAGGG ACAAATTCCC AGCTGACGGG GACCACAACC TGGATTCCCT GCCCACCCTG GCCATGAGTG CGGGGGCACT GGGAGCTCTA CAGCTCCCAG GTGTGCTGAC 40 AAGGCTGCGA GCGGACCTAC TGTCCTACCT GCGGCACGTG CAGTGGCTGC GCCGGGCAGG TGGCTCTTCC CTGAAGACCC TGGAGCCCGA GCTGGGCACC CTGCAGGCCC GACTGGACCG GCTGCTGCGC CGGCTGCAGC TCCTGATGTC CCGCCTGGCC CTGCCCCAGC CACCCCCGGA CCCGCCGGCG CCCCCGCTGG CGCCCCCCTC CTCAGCCTGG GGGGGCATCA GGGCCGCCCA CGCCATCCTG GGGGGGCTGC ACCTGACACT TGACTGGGCC GTGAGGGGAC TGCTGCTGCT GAAGACTCGG CTGTGACCCG GGGCCCAAAG CCACCACCGT CCTTCCAAAG 45 CCAGATCTTA TTTATTTATT TATTTCAGTA CTGGGGGCGA AACAGCCAGG TGATCCCCCC GCCATTATCT CCCCCTAGTT AGAGACAGTC CTTCCGTGAG GCCTGGGGGA CATCTGTGCC TTATTTATAC TTATTTATTT CAGGAGCAGG GGTGGGAGGC AGGTGGACTC CTGGGTCCCC GAGGAGGAGG GGACTGGGGT CCCGGATTCT TGGGTCTCCA AGAAGTCTGT CCACAGACTT CTGCCCTGGC TCTTCCCCAT CTAGGCCTGG GCAGGAACAT ATATTATTTA TTTAAGCAAT TACTTTTCAT GTTGGGGTGG GGACGGAGGG GAAAGGGAAG CCTGGGTTTT 50 TGTACAAAAA TGTGAGAAAC CTTTGTGAGA CAGAGAACAG GGAATTAAAT GTGTCATACA TATCC CAGCTGCGGC ATCCTCTGTC TCAGAGTCTT GGTGTCTCTG TTCCTTrCCC CTCGGGGTCT CCCTGGGTCT CCCCAAGTCC CTCCTGCTGT CTTCCTCCCG CTCTCTGATC TCTGACTCCC AGAACCTCTC CCTCTGTCTC CAGGGCTGCC CCTCTGATCC TCTTTGCTTC TCTGGTGTGT CTCTCTGGCT GCCTCCATCT CTGTGGATCT CCGTCTCCCT GTCTCTGTCT CAGTCTGTCC TTCACTCTGT GTGTGTGTGT GTCTCTCTCT CTCTCTCTCC 55 TTCCCTTCCA CTCCCTCTTC CTCCTGCCTC CACCTCTCCA GGCCCCTGTC TTGTCCCTCC GTCCGGCCTT TCTCTGCCTT TCCGTCCTCC TGCCTCCCCA TCTCTCTCTG CTAGTCCTGT CCAGCCGGAC CCCCACCCAC AGTCGGGCCC CAGCGCTTGA GCCTGAGTGT CTGCTCCGGC CCGTGGAGGT GGAGGGAGGG GACGCCAATG ACCTCACCAG CCCCTCTCCG ACCACCCCCC CCTCCCTT TTCAACTT CCAACTC CTTCCGTGCC CTCCTCCGAG CGCGGCGGCG TGAGCCCTGC AAGGCAGCCG CTCCGTCTGA ATGGAAAAGG CAGGCAGGGA 60 GGGTGAGTCA GGATGTGTCA GGCCGGCCCT CCCCTGCCGC CTGCCCCCCG CCCGCCCGCC CCAGGCCCCC WO 00/62736 PCT/USOO/08020 237 TATATAACCC CCCAGGCGTC CACACTCCCT CACTGCCGCG GGCCCTGCTG CTCAGGGCAC ATGCCTCCCC TCCCCAGCCG CGGGCCCAGC TGACCCTCGG GGCTCCCCCG GCAGCGGACA GGGAAGGGTT AAAGGCCCCC GGCTCCCTGC CCCCTGCCCT GGGGAACCCC TGGCCCTGTG GGGACATGAA CTGTAAGTTG GTTCATGGGG AGGGTGGAGG GGACAGGGAG GCAGGGAGGA GAGGGACCCA CGGCGGGGGT GGGAGCAGAC CCCGCTGAGT 5 CGCACAGAGA GGGACCCGGA GACAGGCAGC CGGGGAGGAG AGCAGCTTCG GAGACAGGAG GCGGCGGAGG AGATGGGCAG AGAGAGACAC AGACAGGAGC GGATGGAGGC AGCCAATCAG AGGCGCCGCA GGAGGGACGG GCCAGACAGG GCCCGAGAGG AGCGAGACGC GAGACCGAGC AGGGGCAGGG ACGCAGGGAC TGGTGCCGGG AGGGAGGTGA CCCCCATCGA CCCAGGCCCC AGGGAGCCCG CGGGGACCGG GAGACTCCCT GGGATTCCGG CAGAGAGGCT CCGGAGGGAA ACTGAGGCAG GGTCCGCGGA GAGCGGAGCA AGCCAGGGAG TAGCGACCCC 10 AGCCGGGGGG AGGAGAGAGA CTGGGCGCCG GGGGAAAGCG GGGAGAGCCG GGCAGATGCG GCCGACGGAG GCGCGGACAG ACCGACGGCT GGCGGGCCCG GGGGGCGGGC TGGGGGTGTG CGAGGCGCGG GCGGCCGGGG AGCGCTGATT GGCTGGCGGG TGGCCGGGTG GGCGGGGCGG CCGGGGTGGG CTGCGGGGAG CGAGCTCCGG ACCCCCGCGC CCCCGGCGCC CCCCGCGCCC CCCGCCGCCA GCTCTCCCGC TCCCGGCGCC CGGCCGGGCC ATGGCTCTGC CCCTCTCCGC CCAGGTGCGC TGCGGCCCGG GCTTCTGCCG CCCACCCGGC GGGCTCCTGG 15 GAGGGCGTCT AAGGGGTCTC CCGTGGGAGA GGTCCGTGTC TCCCGGACTC CGTCCTGGGC TITTGGCTCC TTCCCCTGCT CCCAGCCAGC TCGGGCTCCC GCGGCCCGGG GAGGGGGCAG GTTCTGGCCT GTGCCTCCCC CACCATCCGC GCCCCGGGGC CCAGATTCCG GCGTCCGGGG GCGGACGGGA GACGCCCGGG CCGCGTCTGC TCCGACGGGC GGGGCAGCCA GAGCCAGGGA GGGAGAGGGA AGCCCGCCTG GCCCTGCGAC CTGCCCGCGG GCGTTCCACC CTGGGACTTA AGACCTCCAG CTCCATCCTC CCTAAGGCCG GGAGTCCAGG CCCCAGACCC 20 TCCTCCCCGA GACCCAGGAG TCCAGACCCC AGGCCTTCCT CCCTCAGACC TAGGAGTCCA GGCCCCCAGC CTCTCCTCCC TCAGACCCAG GAGGAGTCCA GACCCCAGTT CCTCCTCCCT CAGACCCGGG AGTCCAGCCC AGGCCCTCCT CTCTCAGACC CGGAGTCCAG CCTGAGCTCT CTGCCTTATC CTGCCCCCAG GTGTTTGCCG CCTGGTCCTG GTCGTGCTGA GCCTGTGGCC AGATACAGCT GTCGCCCCTG GGCCACCACC TGGCCCCCCT CGAGTCCC CAGACCCTCG GGCCGAGCTG GACAGCACCG TGCTCCTGAC CCGCTCTCTC CTGGCGGACA 25 CGCGGCAGCT GGCTGCACAG CTGGTAGGAG AGACTGGGCT GGGGCCAGCA CAGGAGTGAG AGGCAGAGAG GAACGGAGAG GAGTCTGCGG GCAGCCACTT GGAGGGGTTC TGGGCTCTCA GGTGGCAGAG TGAGGGAGGG GAAGAGTTGG GGGCCTGGCG TGGGGGATGG AGGGAGCCCC GAGGCTGGGC AGGGGCCACC TCACAGCTT TTCCCTGCC AGAGGGACAA ATTCCCAGCT GACGGGGACC ACAACCTGGA TTCCCTGCCC ACCCTGGCCA TGAGTGCAGG GGCACTGGGA GCTCTACAGG TAAGGGCAAG GGAGTGGGCT GGGGACAAGG TGGGAGGCAG 30 GCAGTGAAGG GGGCGGGGAG GATGAGGGGC ACTGGTCGGG TGTTCTCTGA TGTCCCGGCT CTATCCCCAG CTCCCAGGTG TGCTGACAAG GCTGCGAGCG GACCTACTGT CCTACCTGCG GCACGTGCAG TGGCTGCGCC GGGCAGGTGG CTCTTCCCTG AAGACCCTGG AGCCCGAGCT GGGCACCCTG CAGGCCCGAC TGGACCGGCT GCTGCGCCGG CTGCAGCTCC TGGTATGTCC TGGCCCCAAG ACCTGACACC CCAGACCCCC ACCCCTGGCC CCAAAATCCT GTGGCCTGAG TCCTTGAAGC CTGAGACCCC AGACCCGAGT GCAACAGCCC CGCTCTGAGA 35. CCCTGACACC CTAACAGCCC GCTCTGAGAC CCTGACACCG TAACAGCCCC GCTCTGAGAC CCTGACCCTA ACAGTCCTGC TCTGAGACCC TGACCCTGCA GTCCCAAGAT CCTGTGGCCC TGAGACCCTG AGGCCCTAGA CCCCCAAATC CTGCCCAGAA ACTTCAAATT CTCACCCAAG ACCCTGAGAC TCCATCATCC ATGACCTCAA AGTCCCCAGA TCCCAGCCCC TAAGACCCAA GACCCCATCC TGAAGCCCAA AGCCTTGAGA ATTCAAATCC TCACCTCAAG ACTTGGAGAC CCTGGCCCCA TGACATTGAA AACCATGGAC CTGGCCAGGC GTGGTGGCTC 40 ACGCCTGTAA TCCCAGCACT TTGGGAGGCC GAGGCAAGTG GATCACCTGA GGTCGGGAGT TCAAGACCAG CCAGACCAAC ATGGTGAAAC CCTGTCTCTA CTAAAAATAC AAAATTAGCC AGGCGTGGTG GTGCATGCCT GTAATCCCAG CTACTTGGGA GGCTGAGGCA GGAGAATCGC TTGAACCTGG GAGGCGGAGG TTGCAGTGAG CCGAGATCGC ACCATTACAC TCCAGCCTGG GCAACAAGAG CAAAACTCCC TCTCTCTCAA AAAAAAAAAA AAAAAAAAAA AAGAAGGAAA AGAAAACCAT GGACCTCCAG ACCCTGAGAC CCCAGGCCCC AGCCCTGAGA 45 TCCTGACATC TTAAAGATCC CAGGCCCTAA GATACAAGAC CTTGACCCAA AGCCAGCCrT GGGACCCTGG CTGTACAAAC CCAAGACCTC CAGGACCTAG ACCCCGAGCC CTGAGGCCCT ATGTCTCACT CCCAACATCG AAAACCCTGA CACCTCAGAT CCTGAGCCTG CGCCTGTACG ACTCCAAGAC CCTCACTTCC AAAGCCAGGC CCAAAGCCCT GAGACCAGAA GACTTCAAAC CCTGGTTCTT GGGCCTAACT CCAAAGACCC TGGATCTCAA ATTCCAACTT CTAGCTCTGA GACTCCAGCC CTCACCCATG AGTTCCTGAA CTTGAACCCA GAGACCCCAT 50 CTCTAAGACT TCAGCCTTGA GATCCAGGGC CTGACCCTAG ACTCGAGCCC ACAGACCTCA GATACTGTCT GTAAAACCCC AGCTCTGGTG GGGAGCAGTG GCTCACTCCT GTAATCCCAA GGCAGGGGAG GCCAAGGCAG AAGGACCTCT TGAGGCCATG AGTTTGAGAC AGCCTGGGCA GCATAGCAAG ACTCTGTTTC TTAATTATTA TTATTATTAT TATrTTGG AGACAGAGTC TCGCGCTCTG TrGCCCAGGC TAGAGTGCAA TGGTGCCATT TCGGCTTGCT GGAACCTCCG CCTCCTGGGC TCAAGCGATT CTCCTGCCTC AGCCTCCTGA GTAGCTGGGA 55 CTTCAGGTGC ACACTGCCAC ACCCGGATAA TTTTGTA TTTTAGTAGA CACAGGGTTT CACCGTGTFG CCCAGGCTGG TCACAAACTC CTGAGCTCAG GCCATCCGCC CGCCTCGGCC TCCCAAAGCG CTGGGATAAC WO 00/62736 PCT/USOO/08020 238 AGGCGTGACG CCGCGCCTGG CTTCTTAATT GTTCTAACAG CAGCGACAAC AACAAAAACC CAGCTCTGAG ATTCCAGCCC CGGCGACTCT AACAGTCCCA GGCCCGATCC CTCACCTAGA ACCGAGATGC CAGCCCTGAC TCCACAGACT TCACCCCCAA CCCCCACACT CAGCTCTGGA AGCCCGTCCT GACTCCAGCC TCCATTTTCG GAACCCCACA GCCTGAAGAG CTCCCGGCCT AAACACTTCA CCCCACGCGC CACAGTCCCC CTGTGAATAT 5 GCAGCCCCGA TTCAGCTGCA GCTCCACAGC ACCCCTGCCC TGCACCCCCG CTGCACCCCC TACCTGTGAC TCACCTCTCT CCTCTCCCCA CAGATGTCCC GCCTGGCCCT GCCCCAGCCA CCCCCGGACC CGCCGGCGCC CCCGCTGGCG CCCCCCTCCT CAGCCTGGGG GGGCATCAGG GCCGCCCACG CCATCCTGGG GGGGCTGCAC CTGACACTTG ACTGGGCCGT GAGGGGACTG CTGCTGCTGA AGACTCGGCT GTGACCCGGG GCCCAAAGCC ACCACCGTCC TTCCAAAGCC AGATCTTATT TATTTATTTA TTTCAGTACT GGGGGCGAAA CAGCCAGGTG 10 ATCCCCCCGC CATTATCTCC CCCTAGTTAG AGACAGTCCT TCCGTGAGGC CTGGGGGGCA TCTGTGCCTT ATTATACTT ATTTATTTCA GGAGCAGGGG TGGGAGGCAG GTGGACTCCT GGGTCCCCGA GGAGGAGGGG ACTGGGGTCC CGGATrCTTG GGTCTCCAAG AAGTCTGTCC ACAGACTTCT GCCCTGGCTC TTCCCCATCT AGGCCTGGGC AGGAACATAT ATTATTTATT TAAGCAATTA CTTTTCATGT TGGGGTGGGG ACGGAGGGGA AAGGGAAGCC TGGGTTTG TACAAAAATG TGAGAAACCT TTGTGAGACA GAGAACAGGG AATTAAATGT 15 GTCATACATA TCCACTTGAG GGCGATTTGT CTGAGAGCTG GGGCTGGATG CTTGGGTAAC TGGGGCAGGG CAGGTGGAGG GGAGACCTCC ATTCAGGTGG AGGTCCCGAG TGGGCGGGGC AGCGACTGGG AGATGGGTCG GTCACCCAGA CAGCTCTGTG GAGGCAGGGT CTGAGCCTTG CCTGGGGCCC CGCACTGCAT AGGGCCGTT GTTTGTTT TGAGATGGAG TCTCGCTCTG TTGCCTAGGC TGGAGTGCAG TGAGGCAATC TAAGGTCACT GCAACCTCCA CCTCCCGGGT TCAAGCAATT CTCCTGCCTC AGCCTCCCGA TTAGCTGGGA TCACAGGTGT 20 GCACCACCAT GCCCAGCTAA TTATTTATTT CTTGTATT TTTAGTAGAG ACAGGGTTTC ACCATGTTGG CCAGGCTGGT TTCGAACTCC TGACCTCAGG TGATCCTCCT GCCTCGGCCT CCCAAAGTGC TGGGATTACA GGTGTGAGCC ACCACACCTG ACCCATAGGT CTTCAATAAA TATTTAATGG AAGGTTCCAC AAGTCACCCT GTGATCAACA GTACCCGTAT GGGACAAAGC TGCAAGGTCA AGATGGTTCA TTATGGCTGT GTTCACCATA GCAAACTGGA AACAATCTAG ATATCCAACA GTGAGGGTTA AGCAACATGG TGCATCTGTG GATAGAACGC 25 CACCCAGCCG CCCGGAGCAG GGACTGTCAT TCAGGGAGGC TAAGGAGAGA GGCTTGCTTG GGATATAGAA AGATATCCTG ACATTGGCCA GGCATGGTGG CTCACGCCTG TAATCCTGGC ACTTTGGGAG GACGAAGCGA GTGGATCACT GAAGTCCAAG AGT1GAGAC CGGCCTGCGA GACATGGCAA AACCCTGTCT CAAAAAAGAA AGAATGATGT CCTGACATGA AACAGCAGGC TACAAAACCA CTGCATGCTG TGATCCCAAT TTTGTGTTTT TCTTTCTATA TATGGATTAA AACAAAAATC CTAAAGGGAA ATACGCCAAA ATGTTGACAA TGACTGTCTC 30 CAGGTCAAAG GAGAGAGGTG GGATTGTGGG TGACTTTTAA TGTGTATGAT TGTCTGTATT TTACAGAATT TCTGCCATGA CTGTGTATTT TGCATGACAC ATTTTAAAAA TAATAAACAC TATITTAGA ATAACAGAAT ATCAGCCTCC TCCTCTCCAA AAATAAGCCC TCAGGAGGGG ACAAAGTTGA CCGCTGATTG AGCCTGTCAG GGCTGTGCAC-3' (FRAG. NO:_)(SEQ. ID NO:2523) 5'-GCTCAGGGCA CATGCCTCCC CTCCCCAGGC CGCGGCCCAG CTGACCCTCG GGGCTCCCCC GGCAGCGGAC 35 AGGGAAGGGT TAAAGGCCCC CGGCTCCCTG CCCCCTGCCC TGGGGAACCC CTGGCCCTGT GGGGACATGA ACTGTGTTTG CCGCCTGGTC CTGGTCGTGC TGAGCCTGTG GCCAGATACA GCTGTCGCCC CTGGGCCACC ACCTGGCCCC CCTCGAGTTT CCCCAGACCC TCGGGCCGAG CTGGACAGCA CCGTGCTCCT GACCCGCTCT CTCCTGGCGG ACACGCGGCA GCTGGCTGCA CAGCTGAGGG ACAAATTCCC AGCTGACGGG GACCACAACC TGGATTCCCT GCCCACCCTG GCCATGAGTG CGGGGGCACT GGGAGCTCTA CAGCTCCCAG GTGTGCTGAC 40 AAGGCTGCGA GCGGACCTAC TGTCCTACCT GCGGCACGTG CAGTGGCTGC GCCGGGCAGG TGGCTCTTCC CTGAAGACCC TGGAGCCCGA GCTGGGCACC CTGCAGGCCC GACTGGACCG GCTGCTGCGC CGGCTGCAGC TCCTGATGTC CCGCCTGGCC CTGCCCCAGC CACCCCCGGA CCCGCCGGCG CCCCCGCTGG CGCCCCCCTC CTCAGCCTGG GGGGGCATCA GGGCCGCCCA CGCCATCCTG GGGGGGCTGC ACCTGACACT TGACTGGGCC GTGAGGGGAC TGCTGCTGCT GAAGACTCGG CTGTGACCCG GGGCCCAAAG CCACCACCGT CCTTCCAAAG 45 CCAGATCTTA TTTATTTATT TATTTCAGTA CTGGGGGCGA AACAGCCAGG TGATCCCCCC GCCATTATCT CCCCCTAGTT AGAGACAGTC CTTCCGTGAG GCCTGGGGGA CATCTGTGCC TTATTTATAC TTATTATTT CAGGAGCAGG GGTGGGAGGC AGGTGGACTC CTGGGTCCCC GAGGAGGAGG GGACTGGGGT CCCGGATTCT TGGGTCTCCA AGAAGTCTGT CCACAGACTT CTGCCCTGGC TCTTCCCCAT CTAGGCCTGG GCAGGAACAT ATATTAYTA TTTAAGCAAT TACTTTTCAT GTTGGGGTGG GGACGGAGGG GAAAGGGAAG CCTGGGTTTT 50 TGTACAAAAA TGTGAGAAAC CTTTGTGAGA CAGAGAACAG GGAATrAAAT GTGTCATACA TATCC-3' (FRAG. NO:_)(SEQ. ID NO:2521) 5'-CAGCTGCGGC ATCCTCTGTC TCAGAGTCTT GGTGTCTCTG TTCCTTTCCC CTCGGGGTCT CCCTGGGTCT CCCCAAGTCC CTCCTGCTGT CTTCCTCCCG CTCTCTGATC TCTGACTCCC AGAACCTCTC CCTCTGTCTC CAGGGCTGCC CCTCTGATCC TCTTTGCTTC TCTGGTGTGT CTCTCTGGCT GCCTCCATCT CTGTGGATCT 55 CCGTCTCCCT GTCTCTGTCT CAGTCTGTCC TTCACTCTGT GTGTGTGTGT GTCTCTCTCT CTCTCTCTCC TTCCCTTCCA CTCCCTCTTC CTCCTGCCTC CACCTCTCCA GGCCCCTGTC TTGTCCCTCC GTCCGGCCrr TCTCTGCCTT TCCGTCCTCC TGCCTCCCCA TCTCTCTCTG CTAGTCCTGT CCAGCCGGAC CCCCACCCAC AGTCGGGCCC CAGCGCTTGA GCCTGAGTGT CTGCTCCGGC CCGTGGAGGT GGAGGGAGGG GACGCCAATG ACCTCACCAG CCCCTCTCCG ACCACCCCCC CCTCCCTT TTCAACTTTT CCAACTTC CTTCCGTGCC 60 CTCCTCCGAG CGCGGCGGCG TGAGCCCTGC AAGGCAGCCG CTCCGTCTGA ATGGAAAAGG CAGGCAGGGA WO 00/62736 PCT/USOO/08020 239 GGGTGAGTCA GGATGTGTCA GGCCGGCCCT CCCCTGCCGC CTGCCCCCCG CCCGCCCGCC CCAGGCCCCC TATATAACCC CCCAGGCGTC CACACTCCCT CACTGCCGCG GGCCCTGCTG CTCAGGGCAC ATGCCTCCCC TCCCCAGCCG CGGGCCCAGC TGACCCTCGG GGCTCCCCCG GCAGCGGACA GGGAAGGGTT AAAGGCCCCC GGCTCCCTGC CCCCTGCCCT GGGGAACCCC TGGCCCTGTG GGGACATGAA CTGTAAGTTG GTTCATGGGG 5 AGGGTGGAGG GGACAGGGAG GCAGGGAGGA GAGGGACCCA CGGCGGGGGT GGGAGCAGAC CCCGCTGAGT CGCACAGAGA GGGACCCGGA GACAGGCAGC CGGGGAGGAG AGCAGCTTCG GAGACAGGAG.GCGGCGGAGG AGATGGGCAG AGAGAGACAC AGACAGGAGC GGATGGAGGC AGCCAATCAG AGGCGCCGCA GGAGGGACGG GCCAGACAGG GCCCGAGAGG AGCGAGACGC GAGACCGAGC AGGGGCAGGG ACGCAGGGAC TGGTGCCGGG AGGGAGGTGA CCCCCATCGA CCCAGGCCCC AGGGAGCCCG CGGGGACCGG GAGACTCCCT GGGATTCCGG 10 CAGAGAGGCT CCGGAGGGAA ACTGAGGCAG GGTCCGCGGA GAGCGGAGCA AGCCAGGGAG TAGCGACCCC AGCCGGGGGG AGGAGAGAGA CTGGGCGCCG GGGGAAAGCG GGGAGAGCCG GGCAGATGCG GCCGACGGAG GCGCGGACAG ACCGACGGCT GGCGGGCCCG GGGGGCGGGC TGGGGGTGTG CGAGGCGCGG GCGGCCGGGG AGCGCTGATT GGCTGGCGGG TGGCCGGGTG GGCGGGGCGG CCGGGGTGGG CTGCGGGGAG CGAGCTCCGG ACCCCCGCGC CCCCGGCGCC CCCCGCGCCC CCCGCCGCCA GCTCTCCCGC TCCCGGCGCC CGGCCGGGCC 15 ATGGCTCTGC CCCTCTCCGC CCAGGTGCGC TGCGGCCCGG GCTTCTGCCG CCCACCCGGC GGGCTCCTGG GAGGGCGTCT AAGGGGTCTC CCGTGGGAGA GGTCCGTGTC TCCCGGACTC CGTCCTGGGC TTTGGCTCC TJTCCCCTGCT CCCAGCCAGC TCGGGCTCCC GCGGCCCGGG GAGGGGGCAG GTTCTGGCCT GTGCCTCCCC CACCATCCGC GCCCCGGGGC CCAGATTCCG GCGTCCGGGG GCGGACGGGA GACGCCCGGG CCGCGTCTGC TCCGACGGGC GGGGCAGCCA GAGCCAGGGA GGGAGAGGGA AGCCCGCCTG GCCCTGCGAC CTGCCCGCGG 20 GCGTTCCACC CTGGGACTTA AGACCTCCAG CTCCATCCTC CCTAAGGCCG GGAGTCCAGG CCCCAGACCC TCCTCCCCGA GACCCAGGAG TCCAGACCCC AGGCCTTCCT CCCTCAGACC TAGGAGTCCA GGCCCCCAGC CTCTCCTCCC TCAGACCCAG GAGGAGTCCA GACCCCAGTT CCTCCTCCCT CAGACCCGGG AGTCCAGCCC AGGCCCTCCT CTCTCAGACC CGGAGTCCAG CCTGAGCTCT CTGCCTTATC CTGCCCCCAG GTGTTTGCCG CCTGGTCCTG GTCGTGCTGA GCCTGTGGCC AGATACAGCT GTCGCCCCTG GGCCACCACC TGGCCCCCCT 25 CGAGTrTCCC CAGACCCTCG GGCCGAGCTG GACAGCACCG TGCTCCTGAC CCGCTCTCTC CTGGCGGACA CGCGGCAGCT GGCTGCACAG CTGGTAGGAG AGACTGGGCT GGGGCCAGCA CAGGAGTGAG AGGCAGAGAG GAACGGAGAG GAGTCTGCGG GCAGCCACTT GGAGGGGTTC TGGGCTCTCA GGTGGCAGAG TGAGGGAGGG GAAGAGTTGG GGGCCTGGCG TGGGGGATGG AGGGAGCCCC GAGGCTGGGC AGGGGCCACC TCACAGCTT TTTCCCTGCC AGAGGGACAA ATTCCCAGCT GACGGGGACC ACAACCTGGA TTCCCTGCCC ACCCTGGCCA 30 TGAGTGCAGG GGCACTGGGA GCTCTACAGG TAAGGGCAAG GGAGTGGGCT GGGGACAAGG TGGGAGGCAG GCAGTGAAGG GGGCGGGGAG GATGAGGGGC ACTGGTCGGG TGTTCTCTGA TGTCCCGGCT CTATCCCCAG CTCCCAGGTG TGCTGACAAG GCTGCGAGCG GACCTACTGT CCTACCTGCG GCACGTGCAG TGGCTGCGCC GGGCAGGTGG CTCTTCCCTG AAGACCCTGG AGCCCGAGCT GGGCACCCTG CAGGCCCGAC TGGACCGGCT GCTGCGCCGG CTGCAGCTCC TGGTATGTCC TGGCCCCAAG ACCTGACACC CCAGACCCCC ACCCCTGGCC 35 CCAAAATCCT GTGGCCTGAG TCCTTGAAGC CTGAGACCCC AGACCCGAGT GCAACAGCCC CGCTCTGAGA CCCTGACACC CTAACAGCCC GCTCTGAGAC CCTGACACCG TAACAGCCCC GCTCTGAGAC CCTGACCCTA ACAGTCCTGC TCTGAGACCC TGACCCTGCA GTCCCAAGAT CCTGTGGCCC TGAGACCCTG AGGCCCTAGA CCCCCAAATC CTGCCCAGAA ACTTCAAATT CTCACCCAAG ACCCTGAGAC TCCATCATCC ATGACCTCAA AGTCCCCAGA TCCCAGCCCC TAAGACCCAA GACCCCATCC TGAAGCCCAA AGCCTTGAGA ATTCAAATCC 40 TCACCTCAAG ACTTGGAGAC CCTGGCCCCA TGACATTGAA AACCATGGAC CTGGCCAGGC GTGGTGGCTC ACGCCTGTAA TCCCAGCACT TTGGGAGGCC GAGGCAAGTG GATCACCTGA GGTCGGGAGT TCAAGACCAG CCAGACCAAC ATGGTGAAAC CCTGTCTCTA CTAAAAATAC AAAATTAGCC AGGCGTGGTG GTGCATGCCT GTAATCCCAG CTACTTGGGA GGCTGAGGCA GGAGAATCGC TTGAACCTGG GAGGCGGAGG TTGCAGTGAG CCGAGATCGC ACCAT7ACAC TCCAGCCTGG GCAACAAGAG CAAAACTCCC TCTCTCTCAA AAAAAAAAAA 45 AAAAAAAAAA AAGAAGGAAA AGAAAACCAT GGACCTCCAG ACCCTGAGAC CCCAGGCCCC AGCCCTGAGA TCCTGACATC TTAAAGATCC CAGGCCCTAA GATACAAGAC CTTGACCCAA AGCCAGCCTT GGGACCCTGG CTGTACAAAC CCAAGACCTC CAGGACCTAG ACCCCGAGCC CTGAGGCCCT ATGTCTCACT CCCAACATCG AAAACCCTGA CACCTCAGAT CCTGAGCCTG CGCCTGTACG ACTCCAAGAC CCTCACTTCC AAAGCCAGGC CCAAAGCCCT GAGACCAGAA GACTTCAAAC CCTGGTTCTT GGGCCTAACT CCAAAGACCC TGGATCTCAA 50 ATTCCAACTT CTAGCTCTGA GACTCCAGCC CTCACCCATG AGT7CCTGAA CTTGAACCCA GAGACCCCAT CTCTAAGACT TCAGCCTTGA GATCCAGGGC CTGACCCTAG ACTCGAGCCC ACAGACCTCA GATACTGTCT GTAAAACCCC AGCTCTGGTG GGGAGCAGTG GCTCACTCCT GTAATCCCAA GGCAGGGGAG GCCAAGGCAG AAGGACCTCT TGAGGCCATG AGTGAGAC AGCCTGGGCA GCATAGCAAG ACTCTGTTTC TTAATTATTA TTATTATTAT TATTrTTGG AGACAGAGTC TCGCGCTCTG TTGCCCAGGC TAGAGTGCAA TGGTGCCATT 55 TCGGCTTGCT GGAACCTCCG CCTCCTGGGC TCAAGCGATT CTCCTGCCTC AGCCTCCTGA GTAGCTGGGA CTTCAGGTGC ACACTGCCAC ACCCGGATAA TTTITTGTA TTAGTAGA CACAGGGTTT CACCGTGTTG CCCAGGCTGG TCACAAACTC CTGAGCTCAG GCCATCCGCC CGCCTCGGCC TCCCAAAGCG CTGGGATAAC AGGCGTGACG CCGCGCCTGG CTTCTrAATT GTTCTAACAG CAGCGACAAC AACAAAAACC CAGCTCTGAG ATTCCAGCCC CGGCGACTCT AACAGTCCCA GGCCCGATCC CTCACCTAGA ACCGAGATGC CAGCCCTGAC 60 TCCACAGACT TCACCCCCAA CCCCCACACT CAGCTCTGGA AGCCCGTCCT GACTCCAGCC TCCATTrTCG GAACCCCACA GCCTGAAGAG CTCCCGGCCT AAACACTTCA CCCCACGCGC CACAGTCCCC CTGTGAATAT GCAGCCCCGA TTCAGCTGCA GCTCCACAGC ACCCCTGCCC TGCACCCCCG CTGCACCCCC TACCTGTGAC TCACCTCTCT CCTCTCCCCA CAGATGTCCC GCCTGGCCCT GCCCCAGCCA CCCCCGGACC CGCCGGCGCC CCCGCTGGCG CCCCCCTCCT CAGCCTGGGG GGGCATCAGG GCCGCCCACG CCATCCTGGG GGGGCTGCAC 65 CTGACACTTG ACTGGGCCGT GAGGGGACTG CTGCTGCTGA AGACTCGGCT GTGACCCGGG GCCCAAAGCC ACCACCGTCC TTCCAAAGCC AGATCTTATT TATTTATTTA TTTCAGTACT GGGGGCGAAA CAGCCAGGTG WO 00/62736 PCT/USOO/08020 240 ATCCCCCCGC CATTATCTCC CCCTAGTTAG AGACAGTCCT TCCGTGAGGC CTGGGGGGCA TCTGTGCCTT ATTTATACTT ATTTATTTCA GGAGCAGGGG TGGGAGGCAG GTGGACTCCT GGGTCCCCGA GGAGGAGGGG ACTGGGGTCC CGGATTCTTG GGTCTCCAAG AAGTCTGTCC ACAGACTTCT GCCCTGGCTC TTCCCCATCT AGGCCTGGGC AGGAACATAT ATTATTTATT TAAGCAATTA CTTCATGT TGGGGTGGGG ACGGAGGGGA 5 AAGGGAAGCC TGGGTTTG TACAAAAATG TGAGAAACCT TTGTGAGACA GAGAACAGGG AATrAAATGT GTCATACATA TCCACTTGAG GGCGATTTGT CTGAGAGCTG GGGCTGGATG CTTGGGTAAC TGGGGCAGGG CAGGTGGAGG GGAGACCTCC ATTCAGGTGG AGGTCCCGAG TGGGCGGGGC AGCGACTGGG AGATGGGTCG GTCACCCAGA CAGCTCTGTG GAGGCAGGGT CTGAGCCTTG CCTGGGGCCC CGCACTGCAT AGGGCCGTTT GTTTGTTTTT TGAGATGGAG TCTCGCTCTG TTGCCTAGGC TGGAGTGCAG TGAGGCAATC TAAGGTCACT 10 GCAACCTCCA CCTCCCGGGT TCAAGCAATT CTCCTGCCTC AGCCTCCCGA TTAGCTGGGA TCACAGGTGT GCACCACCAT GCCCAGCTAA TTATTTATTr CTTTTGTATT TTTAGTAGAG ACAGGGTTTC ACCATGTTGG CCAGGCTGGT TTCGAACTCC TGACCTCAGG TGATCCTCCT GCCTCGGCCT CCCAAAGTGC TGGGATTACA GGTGTGAGCC ACCACACCTG ACCCATAGGT CTTCAATAAA TATTTAATGG AAGGTTCCAC AAGTCACCCT GTGATCAACA GTACCCGTAT GGGACAAAGC TGCAAGGTCA AGATGGTTCA TTATGGCTGT GTTCACCATA 15 GCAAACTGGA AACAATCTAG ATATCCAACA GTGAGGGTTA AGCAACATGG TGCATCTGTG GATAGAACGC CACCCAGCCG CCCGGAGCAG GGACTGTCAT TCAGGGAGGC TAAGGAGAGA GGCTTGCTTG GGATATAGAA AGATATCCTG ACATTGGCCA GGCATGGTGG CTCACGCCTG TAATCCTGGC ACTTTGGGAG GACGAAGCGA GTGGATCACT GAAGTCCAAG AGTrTGAGAC CGGCCTGCGA GACATGGCAA AACCCTGTCT CAAAAAAGAA AGAATGATGT CCTGACATGA AACAGCAGGC TACAAAACCA CTGCATGCTG TGATCCCAAT TTTGTGTTT 20 TCTTTCTATA TATGGATTAA AACAAAAATC CTAAAGGGAA ATACGCCAAA ATGTTGACAA TGACTGTCTC CAGGTCAAAG GAGAGAGGTG GGATTGTGGG TGACTTAA TGTGTATGAT TGTCTGTATT TTACAGAATT TCTGCCATGA CTGTGTATTT TGCATGACAC ATTTTAAAAA TAATAAACAC TATTTTTAGA ATAACAGAAT ATCAGCCTCC TCCTCTCCAA AAATAAGCCC TCAGGAGGGG ACAAAGTTGA CCGCTGATTG AGCCTGTCAG GGCTGTGCAC-3' FRAGG. NO: ) (SEQ. ID NO:2522) 25 Human GM-CSF Nucleic Acid and Antisense Oligonucleotide Fragments 5'-CT'TGBGCBGG BBGCTCTGGG GCBGGGBGCT GGCBGGGCCC BGGGGGGTGG CTTCCTGCBC TGTCCBGBGT GCBCTGTGCC BCBGCBGCBG CTGCBGGGCC BTCBGCTTCB TGGGGCTCTG GGTGGCBGGT CCBGCCBTGG GTCTGGGTGG GGCTGGGCTG CBGGCTCCGG GCGGTCCBGCCBTGGGTCTG GGGGCTGGG CTGCBGGCTC CGGGCGGGCG GGTGCGGGCT GCGTGCTGGG GGCTGCCCCG CAGGCCCTGC GGTCCBGCCB TGGGTCTGGG 30 GGCTGGGCTG CBGGCTCCGG GCGGGCGGGT GCGGGCTGCG TGCTGGGGGC TGCCCCGCAG GCCCTGC-3' (FRAG. NO:1847) (SEQ. ID NO: 1860) 5'-GBGCBGG BBG-3' (FRAG. NO:1848) (SEQ. ID NO: 1861) 5'-GCCBCBGCBGCBGC-3' (FRAG. NO:1849) (SEQ. ID NO: 1862) 5'-GGG TGC GGG C-3' (FRAG. NO:1850) (SEQ. ID NO: 1863) 35 5'-GGT CCB GCC BTG GGT CTG GG-3' (FRAG. NO:1300)(SEQ. ID NO:1309) 5'-GGC TGG GCT GCB GGC TCC GG-3' (FRAG. NO:1301)(SEQ. ID NO:1310) 5'-GCG GGC GGG TGC GGG CTG CGT GCT GGG-3' (FRAG. NO:1302)(SEQ. ID NO:1311) 5'-GGC TGC CCC GCA GGC CCT GC-3' (FRAG. NO:1303)(SEQ. ID NO:1312) 5'-Cl7GBGCBGG BBGCTCTGGG GCBGGGBGCT GGCBGGGCCC BGGGGGGTGG CTTCCTGCBC TGTCCBGBGT 40 GCBCTGTGCC BCBGCBGCBG CTGCBGGGCC BTCBGCTTCB TGGGGCTCTG GGTGGCBGGT CCBGCCBTGG GTCTGGGTGG GGCTGGGCTG CBGGCTCCGG GC-3' (FRAG. NO:1851) (SEQ. ID NO: 1864) Human Tumor Necrosis Factor a Antisense Oligonucleotide Fragments 5'-GCBCCGCCTG GBGCCCTGGG GCCCCCCTGT CTTCTTGGGG BGCGCCTCCT CGGCCBGCTC CBCGTCCCGG BTCBTGCTTT CBGTGCTCBT GGTGTCCTTT CCBGGGGBGB GBGGGGCTGG TCCTCTGCTG TCCTTGCTGG 45 TGCTCBTGGT GTCCTTCCG CCCTGGGGCC CCCCTGTCTT CTTGGGGCCT CTTCCCTCTG GGGGCCGTCT CTCTCCCTCT CTTGCGTCTC TCTCTTTCTC TCTCTCTCTT CCCCTTCCC GCTCTTTCTG TCTCGGTGTC TGGTTTTCTC TCTCCGCTGG CTGCCTGTCT GGCCTGCGCT CTTGGCCTGT GCTGTTCCTC CTCCGGTTCC TGTCCTCTCT GTCTGTCGCC CCCTCTGGGG TCTCCCTCTG GGTGGTGGTC TTGTTGCTTG GGCTGGGCTC CGTGTCTCCB GTGCTCBTGG TGTCCGCTGB GGGBGCGTCT GCTGGCGCTG GTCCTCTGCTGTC CTTGCTGGTG 50 CTCBTGGTGT CCTTTCCGCC CTGGGGCCCC CCTGTCTTCT TGGGGCCTCT TCCCTCTGGG GGCCGTCTC TCTCCCTCTC TTGCGTCTCT CTC'ITCTCT CTCTCTCTTC CCCTTTCCCG CTCTTTCTGT CTCGGTGTCT GGTTTTCTCT CTCCGCTGGC TGCCTGTCTG GCCTGCGCTC TTGGCCTGTG CTGTTCCTCC TCCGGTTCCT GTCCTCTCTG TCTGTCGCCC CCTCTGGGGT CTCCCTCTGG CGTGGTGGTC TTGTTGCTTG GGCTGGGCTC CGTGTCTCCB GTGCTCBTGG TGTCCGCTGB GGGBGCGTCT GCTGGC-3' (FRAG.NO:1852)(SEQ.ID NO:1865) 55 5'-GGGGCCCCCC-3' (FRAG. NO:1853) (SEQ. ID NO:1866) 5'- GGG GGC CG TCT-3' (FRAG. NO:1854) (SEQ. ID NO:1867) 5'-CCBGGGGBGB GBGGGGCTGG-3' (FRAG. NO:1855) (SEQ. ID NO:1868) 5'-GCBCCGCCTG GBGCCCTGGG GCCCCCCTGT CTTCTTGGGG BGCGCCTCCT CGGCCBGCTC CBCGTCCCGG BTCBTGCTTT CBGTGCTCBT GGTGTCCTTT CCBGGGGBGB GBGGG-3' (FRAG. NO:1304) (SEQ. ID NO:1313) 60 5'-GCT GGT CCT CTG CTG TCC TTG CTG GTG CTC BTG GTG TCC TTT CC GCC CTG GGG CCC CCC TGT CTT CTT GGG G CCT CTT CCC TCT GGG GGC CG TCT CTC TCC CTC TCT TGC GTC TCT C TCT TTC TCT CTC TCT CTT CCC C TTT CCC GCT CTT TCT GTC TC GGT GTC TGG TTT TCT CTC TCC GCT GGC TGC CTG TCT GGC CTG CGC TCT T GGC CTG TGC TGT TCC TCC TCC GGT TCC TGT CCT CTC TGT CTG TC GCC CCC TCT GGG GTC TCC CTC TGG C GTG GTG GTC TTG TTG CTT GGG CTG GGC TCC GTG TCT C CBG TGC TCB TGG TGT WO 00/62736 PCT/USOO/08020 241 CC-3' (FRAG. NO:1305) (SEQ. ID NO:1314) 5'-GCT GBG GGB GCG TCT GCT GGC GCT GGT CCT CTG CTG TCC TTG CTG GTG CTC BTG GTG TCC TTT CC GCC CTG GGG CCC CCC TGT CTT CTT GGG G CCT CTT CCC TCT GGG GGC CG TCT CTC TCC CTC TCT TGC GTC TCT C TCT TTC TCT CTC TCT CTT CCC C TTT CCC GCT CTT TCT GTC TC GGT GTC TGG TTT TCT CTC 5 TCC GCT GGC TGC CTG TCT GGC CTG CGC TCT T GGC CTG TGC TGT TCC TCC TCC GGT TCC TGT CCT CTC TGT CTG TC GCC CCC TCT GGG GTC.TCC CTC TGG C GTG GTG GTC TTG TrG CTT GGG CTG GGC TCC GTG TCT C CBG TGC TCB TGG TGT CC'GCT GBG GGB GCG TCT GCT GGC-3'(FRAG.NO:1306)(SEQ.ID NO:1315) 5'-GCT GGT CCT CTG CTG TCC TTG CTG-3' (FRAG. NO:1655) (SEQ. ID NO:1664) 5'-GTG CTC BTG GTG TCC TTT CC-3' (FRAG. NO:1656)(SEQ. ID NO:1665) 10 5'-GCC CTG GGG CCC CCC TGT CTT -CTT GGG G-3' (FRAG. NO:1657)(SEQ. ID NO:1666) 5'-CCT CTT CCC TCT GGG GGC CG-3' (FRAG. NO:1658)(SEQ. ID NO:1667) 5'-TCT CTC TCC CTC TCT TGC GTC TCT C-3' (FRAG. NO:1659)(SEQ. ID NO:1668) 5'-TCT TTC TCT CTC TCT CTT CCC C-3' (FRAG. NO:1660)(SEQ. ID NO:1669) 5'-TTT CCC GCT CTT TCT GTC TC-3' (FRAG. NO:1661)(SEQ. ID NO:1670) 15 5'-GGT GTC TGG TTT TCT CTC TCC-3' (FRAG. NO:1662)(SEQ. ID NO:1671) 5'-GCT GGC TGC CTG TCT GGC CTG CGC TCT T-3' (FRAG. NO:1663)(SEQ. ID NO:1672) 5'-GGC CTG TGC TGT TCC TCC-3' (FRAG. NO:1664)(SEQ. ID NO:1673) 5'-TCC GGT TCC TGT CCT CTC TGT CTG TC-3' (FRAG. NO:1665)(SEQ. ID NO:1674) 5'-GCC CCC TCT GGG GTC TCC CTC TGG C-3' (FRAG. NO:1666)(SEQ. ID NO:1675) 20 5'-GTG GTG GTC TTG TTG CTT-3' (FRAG. NO:1667)(SEQ. ID NO:1676) 5'-GGG CTG GGC TCC GTG TCT C-3' (FRAG. NO:1668)(SEQ. ID NO:1677) 5'-CBG TGC TCB TGG TGT CC-3' (FRAG. NO:1669)(SEQ. ID NO:1678) 5'-GCT GBG GGB GCG TCT GCT GGC-3' FRAGG. NO:1670)(SEQ. ID NO:1679) Human Leukotriene C4 Synthase Nucleic Acids and Antisense Oligonucleotide Fragments 25 5'-CTCGGTBGBC GCGCTCGBBC TCGGGTGGGC CGGTGGTGBG CGGCGGCGBCB CGCGGBBGGC CCTGCGCGCC GBGBTCBCCTG CBGGGBGBBG TBGGCTTGCB GCBGGBCTCC CBGGBGGGTG BCBGCBGCCB GTBGBGCTBC CTCGTCCTTC BTGGTBCCGT CGGTGTGGTG GCBCGGGCTG TGTGTGBBGG CGBGCTGGGC CCCGTCTGCT GCTCCTCGTG CCGCCTCGTC CTTCA TGG TA CCGTCGGTGT GGTGGCCTCG GGTGGGCCGG TGGTGGGGCG CGCGCGCTCG CGTGGCTCCG GCTCTTCTT CCCGGCTCCGT CGGCCCGGGG GCCTTGGTCT CCCTCGTCCT 30 TCBTGGTBCC G-3' (FRAG. NO:1856) (SEQ ID NO: 1869) 5'-GCB GCBGGBC-3' (FRAG. NO:1857) (SEQ ID NO: 1870) 5'-CCCGGCTCCG-3' FRAGG. NO:1858) (SEQ ID NO: 1871) 5'-CGGCCCGGGG GCC-3' (FRAG. NO:1859) (SEQ ID NO:1872) 5'-CB CGCGG-3' (FRAG. NO:1860) (SEQ ID NO: 1873) 35 5'-GCC CCG TCT GCT GCT CCT CGT GCC G-3' (FRAG. NO:1307)(SEQ. ID NO:1316) 5'-CCT CGT CCT TCA TGG TAC CGT CGG TGT GGT GGC-3' (FRAG. NO:1308)(SEQ. ID NO:1317) 5'-CTC GGG TGG GCC GGT GGT G-3' FRAGG. NO:1309)(SEQ. ID NO:1318) 5'-GGG CGC GCG CGC TCG CGT-3' FRAGG. NO:1310)(SEQ. ID NO:1319) 5'-GGC TCC GGC TCT TCT TTC CCG GCT CCG TCG GCC CGG GGG CCT TGG TCT C-3'(FRAG.NO:1311)(SEQ.ID 40 NO:1320) 5'-CCT CGT CCT TCB TGG TBC CG-3' (FRAG. NO:1312)(SEQ. ID NO:1321) 5'-CTCGGTBGBC GCGCTCGBBC TCGGGTGGGC CGGTGGTGBG CGGCGGCGBCB CGCGGBBGGC CCTGCGCGCC GBGBTCBCCTG CBGGGBGBBG TBGGCTTGCB GCBGGBCTCC CBGGBGGGTG BCBGCBGCCB GTBGBGCTBC CTCGTCCTTC BTGGTBCCGT CGGTGTGGTG GCBCGGGCTG TGTGTGBBGG CGBGCTGG-3' (FRAG.NO:1861) 45 (SEQ ID NO:1874) Human Endothelin-1 Nucleic Acids and Antisense Oligonucleotide Fragments 5'-BCCGGCGGBG CCGCCBGGGT GGBCTGGGBG TGGGTTTCTC CCCGCCGTTC TCBCCCBCCG CGCTGBGCTC BGCGCCTBBG BCTGCTGTTT CTGGBGCTCC TTGGCBBGCC BCBBBCBGCB GBGBGBBBBT CBTGBGCBBB TBBTCCBTTC TGBBBBBBBG GGBTCBBBBB CCTCCCGTTC CCCGTTCGCC TGGCGCGCGC TGCGGGTTCC 50 TCGTGGGTTT CTCCCCGCCG TTCTCCGGTC TGTTGCCTTT GTGGGCTTCT TGTCTTTTTG GCTGTTCTTT TCCTGCTTGG CGTCTTTTCC TTTCTTTGTG CTCGGTTGTG GGTCCGCTGG TCCTTTGCCC TGTGTGTTTC TGCTGCCCGT TCGCCTGGCG CGCGCTGCGG GTTCCTCGTG GGTTCTCCC CGCCGT7CTC CGGTCTGTTG CCTTT7GTGGG CTTCTTGTCT TTGGCTGT TCTTTTCCTG CTTGGCGTCT TTTCCTTTCT TTGTGCTCGG TTGTGGGTCC GCTGGTCCTT TGCCCTGTGT GTTTCTGCTG-3' (FRAG. NO:1862) (SEQ. ID NO:1875) 55 5'-CCGGCGGBG CCGCCBGGGT GGBC-3' FRAGG. NO:1863) (SEQ. ID NO:1876) 5'-CCGCCBGGG-3' (FRAG. NO:1864) (SEQ. ID NO:1877) 5'-GGCGCGCGC-3' (FRAG. NO:1865) (SEQ. ID NO:1878) 5'-GTGGGTCCGC-3' FRAGG. NO:1866) (SEQ. ID NO:1879) 5'-CCCGTTCGCCTGGCGC-3' (FRAG. NO:1313)(SEQ. ID NO:1322) 60 5'-GCGCTGCGGGTTCCTC-3' (FRAG. NO:1314)(SEQ. ID NO:1323) 5'-GTGGGTfTCTCCCCGCCGTTCTC-3' (FRAG. NO:1315)(SEQ. ID NO:1324) 5'-CGGTCTGTTGCCTTTGTGGG -3' (FRAG. NO:1316)(SEQ. ID NO:1325) 5'-CT'TCT'TGTCTTTTTGGCT-3' (FRAG. NO:1317)(SEQ. ID NO:1326) 5'-GTTCTTTTCCTGCTTGGC-3' (FRAG. NO:1318)(SEQ. ID NO:1327) 65 5'-GTCTTTTCCTTTCTT-3' (FRAG. NO:1319)(SEQ. ID NO:1328) WO 00/62736 PCT/USOO/08020 242 5'-TGTGCTCGGTTGTGGGTC-3' (FRAG. NO:1320)(SEQ. ID NO:1329) 5'-CGCTGGTCCTTTGCC-3' (FRAG. NO:1321)(SEQ. ID NO:1330) 5'-CTGTGTGTTTCTGCTG-3' (FRAG. NO:1322)(SEQ. ID NO:1331) 5'-CCCGTTCGCCTGGCGC-3' (FRAG. NO:1323)(SEQ. ID NO:1332) 5 5'-GCGCTGCGGGTTCCTC-3' (FRAG. NO:1324)(SEQ. ID NO:1333) 5'-GTGGGTTTCTCCCCGCCGTTCTC-3' (FRAG. NO:1325(SEQ. ID NO:1334) 5'-CGGTCTGTTGCCTTTGTGGG-3' (FRAG. NO:1326)(SEQ. ID NO:1335) 5'-CCTrGTCTTTGGCT-3' (FRAG. NO:1327)(SEQ. ID NO:1336) 5'-GTTCTTTTCCTGCTTGGC-3' (FRAG. NO:1328)(SEQ. ID NO:1337) 10 5'-GTCTTCCTTTCTT-3' (FRAG. NO:1329)(SEQ. ID NO:1338) 5'-TGTGCTCGGTTGTGGGTC-3' (FRAG. NO:1330)(SEQ. ID NO:1339) 5'-CGCTGGTCCTTTGCC-3' (FRAG. NO:1331)(SEQ. ID NO:1340) 5'-CTGTGTGTTTCTGCTG-3' (FRAG. NO:1332)(SEQ. ID NO:1341) Endothelin Receptor ET-B Nucleic Acids and Antisense Oligonucleotide Fragments 15 5'-GCCCTGTCGG GCGGGAAGCC TCTCTCCTCT CCCCAGATC CGCGACAGGC CGCAGGCAAG AACCAGCGCA ACCAGGGCGC GTCCGCACAG ACTTGGAGGC GGCTGCATGC TGCTACCTGC TCCAGAAGCG TCCGGTGGCC GCCGCGCC CTGTCGGGCG GGBBGCCTCT CTCCTCTCCC CBGBTCCGCG BCBGGCCGCB GGCBBGBBCC BGCGCBBCCB GGGCGCGTCC GCBCBGBCTT GGBGGCGGCT GCBTGCTGCT BCCTGCTCGGGCG GGBBGCCTCCG GTGGCCGCCG CGCGTCCGGT GGCCGCCGCG CCTCTCTCCT CTCCCCGTGG CCCTGTCGGG 20 CGGGTCCTGC CGTCCTGTCT CCTTTTCTTT TGCTGTCTTG TCTTCCCGTC TCTGCTTT-3' (FRAG. NO: 1867) (SEQ. ID NO: 1880) 5'-CGGGCG GGBBGCC-3' (FRAG. NO: 1868) (SEQ. ID NO: 1881) 5'-CGGGCGGG-3' (FRAG. NO: 1869) (SEQ. ID NO: 1882) 5'-CCGCBCBGBC-3' (FRAG. NO: 1870) (SEQ. ID NO: 1883) 25 5'-GCGTCCGGTGGCCGCCGC-3' (FRAG. NO:1333)(SEQ. ID NO:1342) 5'-GCCTCTCTCCTCTCCCC-3' (FRAG. NO:1334)(SEQ. ID NO:1343) 5'-GTGGCCCTGTCGGGCGGG-3' (FRAG. NO:1335)(SEQ. ID NO:1344) 5'-TCCTGCCGTCCTGTCTCCTTT-3' (FRAG. NO:1336)(SEQ. ID NO:1345) 5'-TCTTTTGCTGTCTTGT-3' (FRAG. NO:1337)(SEQ. ID NO:1346) 30 5'-CTTCCCGTCTCTGCT-3' (FRAG. NO:1338)(SEQ. ID NO:1347) 5'-GCCCTGTCGG GCGGGAAGCC TCTCTCCTCT CCCCAGATC CGCGACAGGC CGCAGGCAAG AACCAGCGCA ACCAGGGCGC GTCCGCACAG ACTTGGAGGC GGCTGCATGC TGCTACCTGC TCCAGAAGCG TCCGGTGGCC GCCGC-3' (FRAG. NO: 1871) (SEQ. ID NO: 1884) 5'-GCCCTGTCGG GCGGGBBGCC TCTCTCCTCT CCCCBGBTCC GCGBCBGGCC GCBGGCBBGB BCCBGCGCB 35 BCCBGGGCGC GTCCGCBCBG BCTTGGBGGC GGCTGCBTGC TGCTBCCTGC TCCBGBBGCG TCCGGTGGCC GCCGC-3' (FRAG. NO: 1872) (SEQ. ID NO: 1885) Endothelin ETA Receptor Nucleic Acids and Antisense Oligonucleotide Fragments 5'-GTCTGTCCTC CCCGTCTCCT CCCACTGCTT CTCCCGGGGG CTTCCCCGGC TTCGGGTGGC CGGTGTCCCG GGCTCCGGCG CGGCGGCGGC TTCGGCTGCG GGTGGGTGGC GCGGGCTGCC GGGTCCGCGC GGCGCCTGGG 40 CCCTTGTGCT GCTTTGCT TGTTCCGTTC TGGCTGCTCC GGTCTGTGTT GTGGTTGTTT TGTTTCTTCT TGGGTGTGGG CCTTGCGGTT TTGGCTGTGG GCCCTTTGGG GCCTTGGCTT CTGGCTCGTC TGTCCTCCCC GTCTCCTCCC ACTGCTTCT CCCGGGGGCT TCCCCGGCTT CGGGTGGCCG GTGTCCCGGG CTCCGGCGCG GCGGCGGCT CGGCTGCGGG TGGGTGGCGC GGGCTGCCGG GTCCGCGCGG CGCCTGGGCC CTTGTGCTGC TTGCTTG TTCCGTTCTG GCTGCTCCGG TCTGTGTTGT GGTrGTTTTG TTTCTTCTTG GGTGTGGGCC 45 TTGCGGTTTT GGCTGTGGGC CCTTTGGGGC CTTGGCTTCT GGCTCCAT CCACATGATT GCTTAGATTT GTGCTGTATC TCTCAGGATT ATCACTGATT ACACATCCAA CCAGTGCCAG CCAAAAGGAT GCCCTGAGGC AAAGGGTTTC CATCTTGAGG CAAATTTGAG GACBTCCBC BTGBTTGCTT BGBTTTGTGC TGTBTCTCTC BGGBTTBTCB CTGBTTBCBC BTCCBBCCBG TGCCBGCCBB BBGGBTGCCC TGBGGCBBBG GGTTTCCBTC TTGBGGCBBB TTGBGGB-3' (FRAG. NO:1873) (SEQ. ID NO: 1886) 50 5'-GBGGCBBBGGG-3' (FRAG. NO:1874) (SEQ. ID NO: 1887) 5'-GCCBGCCBB BBGGB-3' (FRAG. NO:1875) (SEQ. ID NO: 1888) 5'-CGCCTGGGCC C-3' (FRAG. NO:1876) (SEQ. ID NO: 1889) 5'-GTCTGTCCTCCCCGTCTCCTCCC-3' (FRAG. NO:1339)(SEQ. ID NO:1348) 5'-ACTGCTTCTCCCGGGG-3' (FRAG. NO:1340)(SEQ. ID NO:1349) 55 5'-GCTTCCCCGGCTTC-3' (FRAG. NO:1341)(SEQ. ID NO:1350) 5'-GGGTGGCCGGTGTCCCGGGCTCCGGCGCGGCGGC-3' (FRAG. NO:1342)(SEQ. ID NO:1351) 5'-GGCTTCGGCTGC-3' (FRAG. NO:1343)(SEQ. ID NO:1352) 5'-GGGTGGGTGGCGCGG-3' (FRAG. NO:1344)(SEQ. ID NO:1353) 5'-GCTGCCGGGTCCGCGCGGCGCCTGGGCC-3' (FRAG. NO:1345)(SEQ. ID NO:1354) 60 5'-CTTGTGCTGCTTTT-3' (FRAG. NO:1346(SEQ. ID NO:1355) 5'-TGCTrGTTCCGTTC-3' (FRAG. NO:1347)(SEQ. ID NO:1356) 5'-TGGCTGCTCCGGTCTGTGTTGTGGTTGTTTTG-3' (FRAG. NO:1348)(SEQ. ID NO:1357) 5'-TTTCTTCTTGGGTGTGGG-3' (FRAG. NO:1349)(SEQ. ID NO:1358) 5'-CCTTGCGGTTTrGG-3' (FRAG. NO:1350)(SEQ. ID NO:1359) 65 5'-CTGTGGGCCCTTTG-3' (FRAG. NO:1351)(SEQ. ID NO:1360) WO 00/62736 PCT/USOO/08020 243 5'-GGGCCTTGGCTTCTGGCTC-3' (FRAG. NO:1352)(SEQ. ID NO:1361) 5'-CATCCACATG ATTGCTTAGA TTTGTGCTGT ATCTCTCAGG ATTATCACTG ATTACACATC CAACCAGTGC CAGCCAAAAG GATGCCCTGA GGCAAAGGGT TTCCATCTTG AGGCAAATTT GAGGA-3' (FRAG.NO:1353) (SEQ.ID NO:1362) 5 5'-CBTCCBCBTG BTTGCTTBGB TTGTGCTGT BTCTCTCBGG BTTBTCBCTG BTTBCBCBTC CBBCCBGTGC CBGCCBBBBG GBTGCCCTGB GGCBBBGGGT TTCCBTCTTG BGGCBBBTTT GBGGB-3' (FRAG. NO:1354)(SEQ. ID NO:1363) Endothelin Receptor A Nucleic Acid and Antisense Oligonucleotide Fragments 5'-GCCACCATGG AAACCCTTTG CCTCAGGGCA TCCTTTTGGC TGGCACTGGT TGGATGTGTA ATCAGTGATA 10 ATCCTGAGAG ATACAGCACA AATCTAAGCA ATCATGTGGA TGATTTCACC ACTTTTCGTG GCACAGAGCT CAGCTTCCTG GTTACCACTC ATCAACCCAC TAATTGGTC CTACCCAGCA ATGGCTCAAT GCACAACTAT TGCCCACAGC AGACTAAAAT TACTTCAGCT TTCAAATACA TTAACACTGT GATATCTrGT ACTATTCA TCGTGGGAAT GGTGGGGAAT GCAACTCTGC TCAGGATCAT TTACCAGAAC AAATGTATGA GGAATGGCCC CAACGCGCTG ATAGCCAGTC TTGCCCTTGG AGACCTTATC TATGTGGTCA TTGATCTCCC TATCAATGTA 15 TGGCTGGGCG CTGGCCTT GATCACAATG ACTTTGGCGT ATCTTTGC AAGCTGTTCC CCTTTTGCA GAAGTCCTCG GTGGGGATCA CCGTCCTCAA CCTCTGCGCT CTTAGTGTTG ACAGGTACAG AGCAGTTGCC TCCTGGAGTC GTGTTCAGGG AATTGGGATT CCTTTGGTAA CTGCCATTGA AATTGCCTCC ATCTGGATCC TGTCCTTTAT CCTGGCCATT CCTGAAGCGA TTGGCTTCGT CATGGTACCC TTTGAATATA GGGGTGGACA GCATAAAACC TGTATGCTCA ATGCCACATC AAAATTCATG GAGTTCTACC AAGATGTAAA GGACTGGTGG 20 CTCTTCGGGT TCTATTCTG TATGCCCTTG GTGTGCACTG CGATCTTCTA CACCCTCATG ACTGGTGAGA TGTTGAACAG AAGGAATGGC AGCTTGAGAA TTGCCCTCAG TGAACATCTT AAGCAGCGTC GAGAAGTGGC AAAAACAGTT TTCTGCTTGG TTGTAATTT TGCTCTGC TGGTTCCCTC TTCATTTAAG CCGTATATTG AAGAAAACTG TGTATAACGA GATGGACAAG AACCGATGTG AATTACTTAG TTTCTTACTG CTCATGGATT ACATCGGTAT TAACTTGGCA ACCATGAATT CATGTATAAA CCCCATAGCT CTGTATTG TGAGCAAGAA 25 ATTTAAAAAT TGTCCAGT CATGCCTCTG CTGCTGCTGT TACCAGTCCA AAAGTCTGAT GACCTCGGTC CCCATGAACG GAACAAGCAT CCAGTGGAAG AACCACGATC AAAACAACCA CAACACAGAC CGGAGCAGCC ATAAGGACAG CATGAACTGA CCACCCTTAG AAGCACTCCT GAATTCGGGA AAAAGTGAAG GTGTAAAAGC AGCACAAGTG CAATAAGAGA TATTTCCTCA AATGCCTC AAGATGGAAA CCCTTTGCCT CAGGGCATCC TTTTGGCTGG CACTGGTTGG ATGTGTAATC AGTGATAATC CTGAGAGATA CAGCACAAAT CTAAGCAATC 30 ATGTGGATGA TTTCACCACT TTTCGTGGCA CAGAGCTCAG CTTCCTGGTT ACCACTCATC AACCCACTAA TTTGGTCCTA CCCAGCAATG GCTCAATGCA CAACTATTGC CCACAGCAGA CTAAAATTAC TTCAGCTTITC AAATACATTA ACACTGTGAT ATCTTGTACT ATTTrCATCG TGGGAATGGT GGGGAATGCA ACTCTGCTCA GGATCATTTA CCAGAACAAA TGTATGAGGA ATGGCCCCAA CGCGCTGATA GCCAGTCTTG CCCTTGGAGA CCTTATCTAT GTGGTCATTG ATCTCCCTAT CAATGTATTT AAGCTGCTGG CTGGGCGCTG GCCTTGAT 35 CACAATGACT TTGGCGTATT TCTTTGCAAG CTGTTCCCCT TTTGCAGAA GTCCTCGGTG GGGATCACCG TCCTCAACCT CTGCGCTCTT AGTGTTGACA GGTACAGAGC AGTTGCCTCC TGGAGTCGTG TTCAGGGAAT TGGGATTCCT TTGGTAACTG CCATTGAAAT TGTCTCCATC TGGATCCTGT CCTTTATCCT GGCCATTCCT GAAGCGATT7G GCTTCGTCAT GGTACCCTTT GAATATAGGG GTGAACAGCA TAAAACCTGT ATGCTCAATG CCACATCAAA ATTCATGGAG TTCTACCAAG ATGTAAAGGA CTGGTGGCTC TTCGGGTTCT ATTTCTGTAT 40 GCCCTTGGTG TGCACTGCGA TCTTCTACAC CCTCATGACT TGTGAGATGT TGAACAGAAG GAATGGCAGC TTGAGAATTG CCCTCAGTGA ACATCTTAAG CAGCGTCGAG AAGTGGCAAA AACAGTTC TGCTTGGTTG TAATTTGC TCTTTGCTGG TTCCCTCTTC ATTTAAGCCG TATATTGAAG AAAACTGTGT ATAACGAGAT GGACAAGAAC CGATGTGAAT TACTTAGTTT CTTACTGCTC ATGGATTACA TCGGTATTAA CTTGGCAACC ATGAATTCAT GTATAAACCC CATAGCTCTG TATTTGTGA GCAAGAAATT TAAAAATTGT TTCCAGTCAT 45 GCCTCTGCTG CTGCTGTTAC CAGTCCAAAA GTCTGATGAC CTCGGTCCCC ATGAACGGAA CAAGCATCCA GTGGAAGAAC CACGATCAAA ACAACCACAA CACAGACCGG AGCAGCCATA AGGACAGCAT GAACTGACCA CCCTTAGAAG CACTCCTCGG TACTCCCATA ATCCTCTCGG AGAAAAAAAT CACAAGGCAA CTGTGAGTCC GGGAATCTCT TCTCTGATCC TTCTTCCTTA ATTCACTCCC ACACCCAAGA AGAAATGCTT TCCAAAACCG CAAGGGTAGA CTGGTTTATC CACCCACAAC ATCTACGAAT CGTACTTCTT TAATTGATCT AATTTACATA 50 TTCTGCGTGT TGTATTCAGC ACTAAAAAAT GGTGGGAGCT GGGGGAGAAT GAAGACTGTT AAATGAAACC AGAAGGATAT TTACTACTT TGCATGAAAA TAGAGCTTTC AAGTACATGG CTAGCTTA TGGCAGTTCT GGTGAATGTT CAATGGGAAC TGGTCACCAT GAAACTTTAG AGATTAACGA CAAGATTC TACTTTITTT AAGTGATTTT TTTGTCCTTC AGCCAAACAC AATATGGGCT CAAGTCACTT TTATTITGAAA TGTCATTTIGG TGCCAGTATC CCGAATTC GAATTCGGGA AAAAGTGAAG GTGTAAAAGC AGCACAAGTG CAATAAGAGA 55 TATTTCCTCA AATTTGCCTC AAGATGGAAA CCCTTTGCCT CAGGGCATCC TTTGGCTGG CACTGGTTGG ATGTGTAATC AGTGATAATC CTGAGAGATA CAGCACAAAT CTAAGCAATC ATGTGGATGA TTTCACCACT TTTCGTGGCA CAGAGCTCAG CTTCCTGGTT ACCACTCATC AACCCACTAA TTTGGTCCTA CCCAGCAATG GCTCAATGCA CAACTATTGC CCACAGCAGA CTAAAATTAC TTCAGCTTTC AAATACATTA ACACTGTGAT ATCTTGTACT ATTCATCG TGGGAATGGT GGGGAATGCA ACTCTGCTCA GGATCATTFA CCAGAACAAA 60 TGTATGAGGA ATGGCCCCAA CGCGCTGATA GCCAGTCTTG CCCTTGGAGA CCTTATCTAT GTGGTCATTG ATCTCCCTAT CAATGTATTr AAGCTGCTGG CTGGGCGCTG GCCTTTTGAT CACAATGACT TTGGCGTATT TCTTTGCAAG CTGTTCCCCT TTTTGCAGAA GTCCTCGGTG GGGATCACCG TCCTCAACCT CTGCGCTCTT AGTGTrGACA GGTACAGAGC AGTTGCCTCC TGGAGTCGTG TTCAGGGAAT TGGGATTCCT TTGGTAACTG CCATTGAAAT TGTCTCCATC TGGATCCTGT CCTTTATCCT GGCCATTCCT GAAGCGATTG GCTTCGTCAT 65 GGTACCCTTT GAATATAGGG GTGAACAGCA TAAAACCTGT ATGCTCAATG CCACATCAAA ATTCATGGAG WO 00/62736 PCT/US00/08020 244 TTCTACCAAG ATGTAAAGGA CTGGTGGCTC TTCGGGTTCT ATTTCTGTAT GCCCTTGGTG TGCACTGCGA TCTTCTACAC CCTCATGACT TGTGAGATGT TGAACAGAAG GAATGGCAGC TTGAGAATTG CCCTCAGTGA ACATCTTAAG CAGCGTCGAG AAGTGGCAAA AACAGTTC TGCTTGGTTG TAATTTTTGC TCTTTGCTGG TTCCCTCTTC ATTAAGCCG TATATTGAAG AAAACTGTGT ATAACGAGAT GGACAAGAAC CGATGTGAAT 5 TACTTAGTTT CTTACTGCTC ATGGATTACA TCGGTATTAA CTTGGCAACC ATGAATTCAT GTATAAACCC CATAGCTCTG TATTTTGTGA GCAAGAAATT TAAAAATTGT TrCCAGTCAT GCCTCTGCTG CTGCTGTTAC CAGTCCAAAA GTCTGATGAC CTCGGTCCCC ATGAACGGAA CAAGCATCCA GTGGAAGAAC CACGATCAAA ACAACCACAA CACAGACCGG AGCAGCCATA AGGACAGCAT GAACTGACCA CCCTTAGAAG CACTCCTCGG TACTCCCATA ATCCTCTCGG AGAAAAAAAT CACAAGGCAA CTGTGAGTCC GGGAATCTCT TCTCTGATCC 10 TTCTTCCTTA AT7CACTCCC ACACCCAAGA AGAAATGCTT TCCAAAACCG CAAGGGTAGA CTGGTTTATC CACCCACAAC ATCTACGAAT CGTACTTCTT TAATTGATCT AATTTACATA TTCTGCGTGT TGTATTCAGC ACTAAAAAAT GGTGGGAGCT GGGGGAGAAT GAAGACTGTT AAATGAAACC AGAAGGATAT TTACTACTTT TGCATGAAAA TAGAGCTTTC AAGTACATGG CTAGCTTA TGGCAGTTCT GGTGAATGTT CAATGGGAAC TGGTCACCAT GAAACTTTAG AGATTAACGA CAAGA'TTC TACTTTTT AAGTGATT TTTGTCCTTC 15 AGCCAAACAC AATATGGGCT CAAGTCACTT TTATTTGAAA TGTCATGG TGCCAGTATC CCGAATTC-3' (FRAG. NO:-) (SEQ ID NO: 3014) 5'-GAATrCGGGA AAAAGTGAAG GTGTAAAAGC AGCACAAGTG CAATAAGAGA TATTFCCTCA AATTTGCCTC AAGATGGAAA CCCTTTGCCT CAGGGCATCC YTGGCTGG CACTGGTTGG ATGTGTAATC AGTGATAATC CTGAGAGATA CAGCACAAAT CTAAGCAATC ATGTGGATGA TTTCACCACT TTTCGTGGCA CAGAGCTCAG 20 CTrCCTGGTT ACCACTCATC AACCCACTAA TTTGGTCCTA CCCAGCAATG GCTCAATGCA CAACTATTGC CCACAGCAGA CTAAAATTAC TTCAGCTTTC AAATACATTA ACACTGTGAT ATCTTGTACT ATTTTCATCG TGGGAATGGT GGGGAATGCA ACTCTGCTCA GGATCATTTA CCAGAACAAA TGTATGAGGA ATGGCCCCAA CGCGCTGATA GCCAGTCTTG CCCTTGGAGA CCT'ATCTAT GTGGTCATTG ATCTCCCTAT CAATGTATTT AAGCTGCTGG CTGGGCGCTG GCCTTTGAT CACAATGACT TTGGCGTATT TCTTTGCAAG CTGTTCCCCT 25 TTTTGCAGAA GTCCTCGGTG GGGATCACCG TCCTCAACCT CTGCGCTCTT AGTGTTGACA GGTACAGAGC AGTTGCCTCC TGGAGTCGTG TTCAGGGAAT TGGGATTCCT TTGGTAACTG CCATTGAAAT TGTCTCCATC TGGATCCTGT CCTTTATCCT GGCCATTCCT GAAGCGATrG GCTTCGTCAT GGTACCCTTr GAATATAGGG GTGAACAGCA TAAAACCTGT ATGCTCAATG CCACATCAAA ATTCATGGAG TTCTACCAAG ATGTAAAGGA CTGGTGGCTC TTCGGGTTCT ATTTCTGTAT GCCCTTGGTG TGCACTGCGA TCTTCTACAC CCTCATGACT 30 TGTGAGATGT TGAACAGAAG GAATGGCAGC TTGAGAATTG CCCTCAGTGA ACATCTTAAG CAGCGTCGAG AAGTGGCAAA AACAGTC TGCTTGGTTG TAATTTGC TCTTTGCTGG TTCCCTCTTC ATTTAAGCCG TATATTGAAG AAAACTGTGT ATAACGAGAT GGACAAGAAC CGATGTGAAT TACTTAGTTT CTTACTGCTC ATGGATTACA TCGGTAT7AA CTrGGCAACC ATGAATTCAT GTATAAACCC CATAGCTCTG TATTGTGA GCAAGAAATT TAAAAATTGT TTCCAGTCAT GCCTCTGCTG CTGCTGTTAC CAGTCCAAAA GTCTGATGAC 35 CTCGGTCCCC ATGAACGGAA CAAGCATCCA GTGGAAGAAC CACGATCAAA ACAACCACAA CACAGACCGG AGCAGCCATA AGGACAGCAT GAACTGACCA CCCTTAGAAG CACTCCTCGG TACTCCCATA ATCCTCTCGG AGAAAAAAAT CACAAGGCAA CTGTGAGTCC GGGAATCTCT TCTCTGATCC TTCTTCCTTA ATTCACTCCC ACACCCAAGA AGAAATGCTT TCCAAAACCG CAAGGGTAGA CTGGTTTATC CACCCACAAC ATCTACGAAT CGTACTTCTT TAATTGATCT AATTTACATA TTCTGCGTGT TGTATTCAGC ACTAAAAAAT GGTGGGAGCT 40 GGGGGAGAAT GAAGACTGTT AAATGAAACC AGAAGGATAT TTACTAC1TTT TGCATGAAAA TAGAGCTTTC AAGTACATGG CTAGCTTA TGGCAGTTCT GGTGAATGTT CAATGGGAAC TGGTCACCAT GAAACTTTAG AGATTAACGA CAAGATTC TACTTTTTTT AAGTGATTTT TTTGTCCTTC AGCCAAACAC AATATGGGCT CAAGTCACTF TTATTTGAAA TGTCATTTGG TGCCAGTATC CCGAATTC-3' (FRAG. NO:_) (SEQ ID NO: 2482) 5'-GAATTCGGGA AAAAGTGAAG GTGTAAAAGC AGCACAAGTG CAATAAGAGA TATTTCCTCA AATTTGCCTC 45 AAGATGGAAA CCCTTTGCCT CAGGGCATCC TTTTGGCTGG CACTGGTTGG ATGTGTAATC AGTGATAATC CTGAGAGATA CAGCACAAAT CTAAGCAATC ATGTGGATGA TTTCACCACT TTTCGTGGCA CAGAGCTCAG CT'TCCTGGTT ACCACTCATC AACCCACTAA TTTGGTCCTA CCCAGCAATG GCTCAATGCA CAACTATTGC CCACAGCAGA CTAAAATTAC TTCAGCTTTC AAATACATTA ACACTGTGAT ATCTTGTACT ATTTTCATCG TGGGAATGGT GGGGAATGCA ACTCTGCTCA GGATCATTTA CCAGAACAAA TGTATGAGGA ATGGCCCCAA 50 CGCGCTGATA GCCAGTCTTG CCCTrGGAGA CCTTATCTAT GTGGTCATTG ATCTCCCTAT CAATGTATT AAGCTGCTGG CTGGGCGCTG GCCTTTTGAT CACAATGACT TTGGCGTATT TCTTTGCAAG CTGTTCCCCT TTTTGCAGAA GTCCTCGGTG GGGATCACCG TCCTCAACCT CTGCGCTCTT AGTGTTGACA GGTACAGAGC AGTTGCCTCC TGGAGTCGTG TTCAGGGAAT TGGGATTCCT TTGGTAACTG CCATTGAAAT TGTCTCCATC TGGATCCTGT CCTTTATCCT GGCCATTCCT GAAGCGATTG GCTTCGTCAT GGTACCCTTT GAATATAGGG 55 GTGAACAGCA TAAAACCTGT ATGCTCAATG CCACATCAAA ATTCATGGAG TTCTACCAAG ATGTAAAGGA CTGGTGGCTC TTCGGGTTCT ATTTCTGTAT GCCCTTGGTG TGCACTGCGA TCTTCTACAC CCTCATGACT TGTGAGATGT TGAACAGAAG GAATGGCAGC TTGAGAATTG CCCTCAGTGA ACATCTTAAG CAGCGTCGAG AAGTGGCAAA AACAGTTTTC TGCTTGGTTG TAATTTGC TCTTGCTGG TTCCCTCTC ATTTAAGCCG TATATTGAAG AAAACTGTGT ATAACGAGAT GGACAAGAAC CGATGTGAAT TACTTAGTTT CTTACTGCTC 60 ATGGATTACA TCGGTATTAA CTTGGCAACC ATGAATTCAT GTATAAACCC CATAGCTCTG TATTGTGA GCAAGAAATT TAAAAATTGT TTCCAGTCAT GCCTCTGCTG CTGCTGTTAC CAGTCCAAAA GTCTGATGAC CTCGGTCCCC ATGAACGGAA CAAGCATCCA GTGGAAGAAC CACGATCAAA ACAACCACAA CACAGACCGG AGCAGCCATA AGGACAGCAT GAACTGACCA CCCTTAGAAG CACTCCTCGG TACTCCCATA ATCCTCTCGG AGAAAAAAAT CACAAGGCAA CTGTGAGTCC GGGAATCTCT TCTCTGATCC TTCTTCCTTA ATTCACTCCC 65 ACACCCAAGA AGAAATGCTT TCCAAAACCG CAAGGGTAGA CTGGTATC CACCCACAAC ATCTACGAAT CGTACTTCTT TAATTGATCT AATTTACATA 17CTGCGTGT TGTATTCAGC ACTAAAAAAT GGTGGGAGCT WO 00/62736 PCT/US00/08020 245 GGGGGAGAAT GAAGACTGTT AAATGAAACC AGAAGGATAT TTACTACTTT TGCATGAAAA TAGAGCTTTC AAGTACATGG CTAGCTTTTA TGGCAGTTCT GGTGAATGTT CAATGGGAAC TGGTCACCAT GAAACTTTAG AGATTAACGA CAAGATTTTC TACITITIT AAGTGATT TGTCCTTC AGCCAAACAC AATATGGGCT CAAGTCACTT TTATTTGAAA TGTCATTTGG TGCCAGTATC CCGAATTC-3'(FRAG. NO:_) (SEQ ID NO: 2470) 5 5'-GCCACCATGG AAACCCTTTG CCTCAGGGCA TCCIT=GGC TGGCACTGGT TGGATGTGTA ATCAGTGATA ATCCTGAGAG ATACAGCACA AATCTAAGCA ATCATGTGGA TGATTTCACC ACTTTTCGTG GCACAGAGCT CAGCTTCCTG GTTACCACTC ATCAACCCAC TAATTGGTC CTACCCAGCA ATGGCTCAAT GCACAACTAT TGCCCACAGC AGACTAAAAT TACTTCAGCT TTCAAATACA TTAACACTGT GATATCTTGT ACTATTTTCA TCGTGGGAAT GGTGGGGAAT GCAACTCTGC TCAGGATCAT TTACCAGAAC AAATGTATGA GGAATGGCCC 10 CAACGCGCTG ATAGCCAGTC TTGCCCTTGG AGACCTTATC TATGTGGTCA TTGATCTCCC TATCAATGTA TGGCTGGGCG CTGGCCTTT GATCACAATG ACTTTGGCGT ATTCTTTGC AAGCTGTTCC CCTTTTTGCA GAAGTCCTCG GTGGGGATCA CCGTCCTCAA CCTCTGCGCT CTTAGTGTTG ACAGGTACAG AGCAGTTGCC TCCTGGAGTC GTGTTCAGGG AATTGGGATT CCTTTGGTAA CTGCCATTGA AATTGCCTCC ATCTGGATCC TGTCCTTTAT CCTGGCCATT CCTGAAGCGA TTGGCTTCGT CATGGTACCC TTTGAATATA GGGGTGGACA 15 GCATAAAACC TGTATGCTCA ATGCCACATC AAAATTCATG GAGTTCTACC AAGATGTAAA GGACTGGTGG CTCTTCGGGT TCTATTTCTG TATGCCCTTG GTGTGCACTG CGATC17CTA CACCCTCATG ACTGGTGAGA TGTTGAACAG AAGGAATGGC AGCTTGAGAA T7GCCCTCAG TGAACATCTT AAGCAGCGTC GAGAAGTGGC AAAAACAGTT TTCTGCTTGG TTGTAATTT TGCTCTTGC TGGTTCCCTC TTCATTTAAG CCGTATATTG AAGAAAACTG TGTATAACGA GATGGACAAG AACCGATGTG AATTACTTAG TTTCTTACTG CTCATGGATT 20 ACATCGGTAT TAACTTGGCA ACCATGAATT CATGTATAAA CCCCATAGCT CTGTATTTTG TGAGCAAGAA ATTTAAAAAT TGTT7CCAGT CATGCCTCTG CTGCTGCTGT TACCAGTCCA AAAGTCTGAT GACCTCGGTC CCCATGAACG GAACAAGCAT CCAGTGGAAG AACCACGATC AAAACAACCA CAACACAGAC CGGAGCAGCC ATAAGGACAG CATGAACTGA CCACCCTTAG AAGCACTCCT-3' (FRAG. NO:_) (SEQ ID NO: 2469) Substance P Antisense Nucleic Acids and Oligonucleotide Antisense Oligonucleotide Fragments 25 5'-CTGCTGBGGC TTGGGTCTCC GGGCGBTTCT CTGCBGBBGB TGCTCBBBGG GCTCCGGCBG TTCCTCCTTG BTCTGGTCGCT GTCGTBCCBG TCGGBCCBGT BBTTCBGBTC BTCBTTGGCT CCTBTTTCTT CTGCBBBCBG CTGBGTGGBG BCBBGBBBBB BGBCTGCCBB GGCCBCGBGG BTTTCBTGT TGGBTTGC GBCGGBCBGT CCCGCGGGGT GCTGAGTTTC TCTGGTTCCT CCGBGCGCBC GTGGTCGCTC CGCGTTTCTC TGGTTCCTCC GGTCCCGCGG GGTGCTGTCT GGTCGCTGTC GTGGCTTGGG TCTCCGGGCG GTTCCTTCC TTTTCCGC-3' 30 (FRAG. NO:1877) (SEQ ID NO: 1890) 5'-CTCC GGGCGB-3' (FRAG. NO:1878) (SEQ ID NO: 1891) 5'-GGCCBCGBGG-3' (FRAG. NO:1879) (SEQ ID NO: 1892) 5'-GGGTCTCCGGGCG-3' (FRAG. NO:1880) (SEQ ID NO: 1893) 5'-GGG TCTCCGGGCG G-3' (FRAG. NO:1881) (SEQ ID NO:1894) 35 5'-CGTGGTCGCTCCGC-3' (FRAG. NO:1355)(SEQ. ID NO:1364) 5'-GTTTCTCTGGTTCCTCCG-3' (FRAG. NO:1356)(SEQ. ID NO:1365) 5'-GTCCCGCGGGGTGCTG-3' (FRAG. NO:1357)(SEQ. ID NO:1366) 5'-TCTGGTCGCTGTCGT-3' (FRAG. NO:1358)(SEQ. ID NO:1367) 5'-GGCTTGGGTCTCCGGGCG-3' (FRAG. NO:1359)(SEQ. ID NO:1368) 40 5'-GTTTCCTTCCTTTCCGC-3' (FRAG. NO:1360)(SEQ. ID NO:1369) 5'-CTGCTGBGGC TTGGGTCTCC GGGCGBTTCT CTGCBGBBGB TGCTCBBBGG GCTCCGGCBG TTCCTCCTTG BTCTGGTCGCT GTCGTBCCBG TCGGBCCBGT BBTTCBGBTC BTCBTTGGCT CCTBTTTCTT CTGCBBBCBG CTGBGTGGBG BCBBGBBBBB BGBCTGCCBB GGCCBCGBGG BTTCBTGT TGGBTTGC GBCGGBCBGT CCCGCGGGGT GCTGAGTTTC TCTGGTTCCT CCGBGCGCB-3' (FRAG. NO:1882) (SEQ ID NO: 1895) 45 Substance P Receptor Nucleic Acids and Antisense Oligonucleotide Fragments 5'-GGGCTBBGBT GBTCCBCBTC BCTBCCBCGT TGCCCBCCBC BGBGGTCBCC BCBBTGBCCG TGTBGGCBGC TGCCCBBBGG BCBBTTTGCC BGGCTGGTTG CBCGBBCTGB TTGGGTTCCG BGGTGTTBGT GGBGBTGTTT GGGGBGBGGT CTGBGTCCBC CGGGBGGBCG TTBTCCBTT CGBBGCTBGG CGGTBBBGCC CTBCTBTCTG TBCBCBBCCC CCCTCTGCBG CBGBGTCCTG TCGTGGCGCC TGGGGCTCBG GGTCCGGGC TAAGATGATC 50 CACATCACTA CCACGTTGCC CACCACAGAG GTCACCACAA TGACCGTGTA GGCAGCTGCC CAAAGGACAA TTTGCCAGGC TGGTTGCACG AACTGATTGG GTTCCGAGGT GTTAGTGGAG ATGTTTGGGG AGAGGTCTGA GTCCACCGGG AGGACGTTAT CCATTTCGAA GCTAGGCGGT AAAGCCCTAC TATCTGTACA CAACCCCCCT CTGCAGCAGA GTCCTGTCGT GGCGCCTGGG GCTCAGGGTC CGTCCTGTCG TGGCGCCTGG GGCTCTTCTT TTGTGGGCTC TTTGGTGGCT GTGGCTGTGG TCTCTGTGGT TGCTGCCCTG GGTCTGGGGG TGTGGCCTTG 55 GGGCCGTCCT CTGGCTCCTC CTCGTGGGCC CCC-3' (FRAG. NO:1883) (SEQ. ID NO:1896) 5'-GGGBGGBCG-3' (FRAG. NO:1884) (SEQ. ID NO:1897) 5'-GGGTC CG-3' (FRAG. NO:1885) (SEQ. ID NO:1898) 5-'GGGCC CCC-3' (FRAG. NO:1886) (SEQ. ID NO:1899) 5'-GTCCTGTCGTGGCGCCTGGGGCTC-3' (FRAG. NO:1361)(SEQ. ID NO:1370) 60 5'-TTCTITTGTGGGCT-3' (FRAG. NO:1362)(SEQ. ID NO:1371) 5'-CTTTGGTGGCTGTGGCTG-3' (FRAG. NO:1363)(SEQ. ID NO:1372) 5'-TGGTCTCTGTGGTTG-3' (FRAG. NO:1364)(SEQ. ID NO:1373) 5'-CTGCCCTGGGTCTGG-3' (FRAG. NO:1365)(SEQ. ID NO:1374) 5'-GGGTGTGGCCTTGGGGCCGTCCTCTGGCTCCTCCTCGTGGGCCCCC (FRAG.NO:1366)(SEQ.ID NO:1375) 65 5'-GGGCTAAGAT GATCCACATC ACTACCACGT TGCCCACCAC AGAGGTCACC ACAATGACCG TGTAGGCAGC WO 00/62736 PCT/USOO/08020 246 TGCCCAAAGG ACAATTTGCC AGGCTGGTTG CACGAACTGA TTGGGTTCCG AGGTGTTAGT GGAGATGT GGGGAGAGGT CTGAGTCCAC CGGGAGGACG TTATCCATC GAAGCTAGGC GGTAAAGCCC TACTATCTGTA CACAACCCCC CTCTGCAGCA GAGTCCTGTC GTGGCGCCTG GGGCTCAGGGTCC-3'(FRAG.NO:1367)(SEQ.ID NO:1376) 5'-GGGCTBBGBT GBTCCBCBTC BCTBCCBCGT TGCCCBCCBC BGBGGTCBCC BCBBTGBCCG TGTBGGCBGC 5 TGCCCBBBGG BCBB'TGCC BGGCTGGTTG CBCGBBCTGB TrGGGTTCCG BGGTGTTBGT GGBGBTGTTT GGGGBGBGGTC TGBGTCCBCC GGGBGGBCGT TBTCCBTTTC GBBGCTBGGC GGTBBBGCCC TBCTBTCTGTB CBCBBCCCCC CTCTGCBGCB GBGTCCTGTC GTGGCGCCTG GGGCTCBGGG TCC-3' (FRAG. NO:1368) (SEQ. ID NO:1377) Chymase Antisense Nucleic Acids and Oligonucleotides Antisense Oligonucleotide Fragments 10 5'-GGBGCTGBTB CTGCBGATTT CBGBGGGBBG BBCCCTGBTB CTCBCCBGCT TCBGCTCTGG BGCBCBBGBG BBBGBGCBGC BGGGGGBGBG GBBGBBGCBG CBTCTTCCCB GBGBGGCTGC CTGBGCBBBT GCTGGTTTTC CTTTCCBGTC TTGGGTTB TBBCTCCCBG BBGGCBBGBG BGGGGCBBGG CGTTCTrC TCTCGCTGGT TTTCCTTTCC TGGCAGTGGG TGGGGGTGGG GGTGGGGTGG CTTCCTTGTT CCTGGGGGTG TCCTCTTGCT CTGGGCTTTT CTCCCCTT CCTTCCTGTC TGTTTrCCTG GGGCTCTCCT CTGTCTCTGT GTCCTGCCC 15 TGGCCCTCTT CCCTCTCCTG TCTCCTGTCC CTGTGTTCCG CCCGTCTTCC CTCTCCTGAC CTCCTTTTCC TCCGCTGGGT GGGGCCCTGC CTGTTCTCTG CTCCCTGGCT TGGGGTTTCT TCTGTGTGTC TTCTTCCTCT GTGGCTGGC TTTCTCCTTC TTTGTCTTC CTGGGTGCCC CTTCTTCCTT TCTTGGGTCC TTGGTGCTTG GGCTGGG TCCCAGTTAA TACATAATCA ATATGCAATT TATTAATACA TCTCTCCATG TCCACTCCCC CTGTATCTTG CCATTCTTGA CCTGCATTTC CATCCTCCTT ACCTTCCCTA 20 GAGGCCAACT CATTTCTTT GAAAAACCTG GCATTTCCCA GAAAAAAAAG TGAAGGGCTG GGAGCTGTCC GTTGTCCTGA TTTGCTCCCT CTGCCCTTGC TTCCAAATGT GGTTGGAAAG AAGCACTATT GAAAAATCCC TAAACGCACC CCTGCAGGGT TGGCTCTACC CTGTAGCCAT GGACACATGC TGTTGATACC ACCTGCCTCA TGAGTCTCAC ATAATTGCC CTTTCACACT ATCTACCCCA TCAGCCTTAC CAAAACCATA CCTGCATCCT GGGCAGCATC TGCCCTTCAA GAGACTAAGG AATCTCCTTG CAACCAAGAA TGACTAGACC AATGAGACAC 25 CCTTTAAGGC CCCAGCACAA TATAGAAATC CCACAATATG GTAATCCCAG TAAGGAGCTA TCAAGCCATT GCAGGACCAT CTAGAATACA ACTAGAGTAT AGTTCCTTTC AATCCAGGAA CTATACTCTA ACAGCTTGGC TCACAGGAAC CAGAAGTGAA GATGATGAGG ATCAGGGCTG AGCCTGTGAG CACCAGCTCC ACCACTGACA CCAACCACAG ATTAAACAAG CATCTTGTGG ACCCCTGGGA TGGAAAGAAT AGTTGTTGCC TTATCAACCT CCCCCACAGC CCACACAGAA AAGATAAAAT CATCATGGCT ACAGTGTTAC AGAAGATGAT GACCCAAGGA 30 GTAGGCCTGC CTGAGTGAAT GCTGAGAGTG ATAATGGGAG CAGTAGCATC TCAGAGACTA CAGCAGAAAC CATCCACATA AAGAGCTTTG CCCAAACTTA TGATAAAGGG CACCCTCAGA GACTCTCCCT ACTAATAT TAGCCCATTG CAGAAATGGT GAGTGGAAAG AGAAATCTTA GGAAGAACCC CTTAAAAAAG CAAAATGCTT TTTAGGTTTG TGCTGAAGAG CCTGGAAAAG AAATAAGGAC ACACACGCTG AGAAATCTTC CTCCTGCCCC AACACTGGGA TAATCTCCAA GGATCTCTCC ATATCTCATT CTCCTGGATA CACTGTCCAC TCAGAAATAT 35 TGTGCAGAGT GCAGTAATTC AAAAGTGAGC TATTGTGTTA GGAGTGAAGG CAAGAGTATC GTAAAATAAA TCAAATTTGA AATGAATTCT CTTAAATTGC TTTATAGATG TTTAATGTAA GCCAGCAGCT ATTAAACGAT AAACCTTAAA TTCGAGAAAA ACTrGGTCAT TCAGAAACTA TAGAAACAGG CAGGACTTAT TGCGAGGGCA AACACAGAGT GAGCTCCAGC CTGCTTCAGG AAAATCTGCC AGTGCCATGA AGGATGTACT CTGTCTGCTC CACTGCACTA CTGCTCAGTA TGAGCCCATG CCATCAGCTG TCCCTGACCC ACAGGAGTTC TTTAGAAGAG 40 ACTGGTCAAC AAAAGTTTCT AGGGTGTTTT ATACCTGCCA ACTCGAGGGT TAAAACAAGT TGCATAGAAA TGCTCAATCA AGAAAGACAC AGTCATTACT CAGAGAATAA TAAACAGCCT GGCAGCACAT GAATGAATAG AAAAAAGATG TTACATGCAA AGCATGAAAT AACCAAATTC CATAACAGAT GTTAATCTGT AATGTGTTTA GGAGAATTTA GAGGAAGTAT AAGATTTATT CTTTCATCAA AAAAATTATA GCCAATGAGG ATATATCTAT CAATTATCCA TCAAGTGGTG ATATGGCAGC ACAAGGTAAA ACACAAAGGA ATAAAACCAA CGTTTATTAA 45 GAACCAATCA TGTGGCATTT CACATTGAGC ATCATATTTA ATTCTGAAAA AAATCCTTGT ACTGTATCAT TCTTCATATT TTATGGATGC AGTAACTAAG GCTGAGAACT TTAAAATT TCCTAAGTFC AGACACATAG CTAAGTGGCA GAACCAAGAT TCAAACTCAC CCCATCTAAC TGCAGAGCAA ACTGCATGCC TTAAATGTCA AAGTGAATAC TAGCACAGTT AATACAATGT TTGGAAACTC AGAGAAGGAA TGATCCCTCT GCATTATAGT TACTAAGGAA TCATTGCCAT TATTTAAATG CCAGTGCTTC TACATCAGGC CCAAATTTTC TGTCCTACTA 50 ACTGTGAATC AAGACTTGAT TCAACCTCTA CTTGAGTATC TGCCGCAATG AGAAATCACT TACCTCCACT AACCACACAT TTATTTTATA ACAACAGATT GTTAGTAAGT CCTTTCTTAT ACATACTCAA CAGCTGCTTC CCAAGATGCT GTAGGATTAT GTCTAGAGTC AAACTAGCCA GAAGCAATGT CCAAAATACA CCATAACACT GTGCAGCAAA GGTCCTACTA CCACTTGT GGCCCAAACA TTCTAGGCAG CACTGGATAT CTGAATCATC AATTATTCC ACAAACACTG ACCCCTCTAC CAGTCACCCT CACTAGAAGA ATTAATTCCA CATGATAATA 55 GCTCCCTCAT GTTACTCCCT TCTAAGTCAA ATTGTACACC CCTTrATCTG ATTAACAGAG TCTAAGTCAC ATGACCTAAA TGCAAGAGAA CTGGGAATGG ACGTTTGTGG ATTCTACCTT AGTAAGGCAA AGTTATCATT GGGAATTCCT CTAATACAGG AAGGGTGTTC CAGAGACATT AAGGAGCCAT ATAAATGGAA AATGTCCACT ACAATCCATC ACTTGGTTGC CCCACATCAA CATTCATTCT TTTGCCACAC TTAAAGTTTC CAAGAACAAA AATTATCCCA CTGAACATAA TCTTTACTAT CTITATATA AAGGAAAATT AGACTTGACT CAGCAGAACT 60 GAAATAACCC AGCTCTAACA GTTACTGCTT TTAACTTCAA GTACTGTGTC TCTAGGTGAT ACCTGCTCCA ACAATAGTTT GGTCACATTT TCAATTTGAT ATTCTCTAGT CTCCCAACTT GATAACTGTA CCCTAAACCA TAAAGTTCAC TACCAACATG CTATATATAA AATAACCAAA GGGGGAAGAA GAAAGAGAAA AAGGAAATCT CTTAAAATAC ACAGGTATAC ATATGACAAA GCAAAGAAGG AAATGTGAGC AGATAGTGCA GTCCTCGTTT CTGAAATTGG TCCCCTGACT GGGGCTATAC CTATTCCATT TCCTCACCCT CAGCCAGGCA GGTGGAGCAA 65 AAACTTAAGT CTTGGTGGAT CTGAATCTTG ATGCTGTGGA GCTGTCTTAC TAGCCCCAGA CTACCTGCCT CTCAATTTCT AATTATATCA GTGAAAGCAA ACAGCTTTGA 'TGTAAG CCTCTGATT TTTGGTCTAA WO 00/62736 PCT/USOO/08020 247 CTGATGTAAG ACCACAAGGA CAAGAGTTCT CCAGCTCCGG ATTCTC'rCT GTrCTGTrAA TGGTGAAATG CCCGAGAGAA GAGTTGCCAA. CTTTGGCAAA TAAAAAATAC AGGA TCCAG TI'AAATTCAA. ATTAGATAA ACAACAATT TTTAGTATTA GTGTGTCCCA TTCAATATIT GGACATACTT AACTAAAAAA TGATGTrG TFCATCTGAA ATACAAA TrT AACTGGGCAT TCTGAATATT C TCTGGCAAC CCCCGAGAGA GTGAAGAAAG 5 TGGTACAAGG ACACTTAAGA AGACCAGA'IT TGAAAAGACA TrACGGATGT G1TTAAATGT CrATTCTAG AGAGAGTTAG AGCTGTAGGT AGAACTI'GGG AAATrAAGTT AAAAGCAGAC ACAGAGACCT GGCCAATATA TACTAAGGAG TGGATCACTC TGGTCACAAG CCCAACCTGA GACCAAGGGC ATAGTGAGAT GATTGGGAA AGGCACTTAT ACACTACTCA TCCCCGTC'IT TGAACTAAAT GCCTFATAAA TCTCCAAGAG AAATGACAGT CCACCATGTG GACTGCTTTC TGTAAGTCCA GGGAAAATAA AAGCTATGTG CTTGAAACCC ACTrCTGATA 10 TTATAAGGTG TGTGATC ITT GTCATGT-rAA TGGGTCTGAG TATCAATTrCT ACAA~rGTAA AGTGACAGTA ATGGTGTGTC CCCAGGrrGT TGTGGAAAGC TTGATTCTTA ATGCAACAGT AGGAAACCCC AGCCTCTCTG GAGCAAACAC CC'ITCTACAT CTACTrCC CCTGCACATT GGCAGGACTC TATTCCTCTA FICTCTCTA GTGCTAGAGC AGAAAGGGAC CTTGATFGA TATCAGGAAA ATCTA'TI'CT GAACCATAAG CTATGAtAGC TGATrAAAA AATTGACTAT CATGACATGA TAATGATCAT AATGGTAATA CATATTGATA GGGTTGCCGT 15 GAAAGTAATA ATATATCTAA GAG'I1GTGAC AATATATGAT ACGCCTAGAC TCTCAGAAAA TGCTAATTCC AATCCCAATfr GCTC'ITTGCA TAAAG'ITCTG TCCTAGGGTC TGTrC'I=C CCACATCTAC CCTCCTIGGA TCTCTC'1CT GTCTTMTCA TGTGGTrCAG AGGAGGAGAG AGATCCAGGT CAATGTrTP CAAATTACAA GGAATTATCA 'I=AAATGGG GAAGAAGCTC AAGTTrGAC GTGTAGTGGA ATTGGAGTGG AGTGGAGTGG AATGGAAACT AACAGGAAGA CACTGCACAT GGTTAAGATA AAGATTGT-I- CCTGAAACCT 'JTAATITGTG 20 cYrACATACT CACACATACA TATGTGCATG CACTGGGACT CTGCAATATG CAT= CTGAC TATGGAACAT AGCCATAAAA GTCMIGCAC TGAACGTTCA GTGGGCCTTT CACAAGCTGC CCTAATTGGG AAAGAAAAAC ATGGTCCCTC CA ITrCCTGC CCCCAACTCC AGAAAAGTCA CCATAGTrGA GGGTACATCT GAGAAGCCAG CACTTGGGAG TTCAGGGCTC AAGTTCCT1 CTAGAAAAAC ACTGGGTGAT TCTAGGGGAA CTTCCGATCA GAAACAGCCA ATrCAGAGTG AGAGAAGAAA ACGTGACCAT GCAG1TCCTG TGGTTACCAG CC I1GCCCCT 25 CTCTrGCCTT CTGGGAGT7A TAAAACCCAA GACTGGAAAG GAAAACCAGC ATTTGCTCAG GCAGCCTCTC TGGGAAGATG CTGCTTCTTC CTCTCCCCCT GCTGCTCTrT CTCTT1GTGCT CCAGAGCTGA AGCTGGTGAG TATCAGGGTT CTTCCCTCTG AAATCTGCAG TATCAGCTrCC TGAAACAAAG ATG'ITTAGTC TGAAATAGCT GACTCCTAAA CAGGG'ITCCA AGATCTCTCT TCAAGAGTCC CACAGAGGAA. ATVTCCACTT GGGATGTGTG CCACCCCACC CCCACCCCCA CCCACTGCCA TTCTCTACAG CCTAGGACAC CCCCAGGAAC AAGGAA3TTC 30 ACCTCAA11G TAGAAAAGCC CAGAGCAAGT GGAAGGAAAA GGGGTATCCC CAGGAAAACA GACATGTCCT CTTAATC'rrC TGAGCATCAG GGCTACCCAT TAC'TrGTGA CTITCTCACT CTGTGACCAT GCTCAAGAGC TATGGAGAAA TCTAAAACAG GAACCTGGAC AGTGGGTCCT ACACAGAGAC AGAGGAGAGT GGGCCAGGGC AAGGTGGGAG TGGGAGAAGT CTGAGATGAA AACATCAGAA TGGAGCAGAG GCAAGAATGA GA'IMCACCT GGGAGGTTAT GGGTGGGGAA AGATACGAAA TACAGGAGAC AGGAGAGGGA AGATGGGCGG AACACAGGGT 35 GAGAATGAGA TTCCAGGGAA GCCTAGCTCA GC1TAACCC ANIT-GTCCA TCATTGGAG AGAGTATCTA TGGCCGTGTT CAAACCCTGG GGTGCTCTGT TCCAGGGGAG ATCATCGGGG GCACAGAATG CAAGCCACAT TCCCGCCCCT ACATGGCCTA CCTGGAAAT7 GTAACTrCCA ACGGTCCCTC AAAATITTGT GGTGGTrTCC TTATAAGACG GAAC'TTGTG CTGACGGCTG CTCATTGTGC AGGAAGGTGA GACAACAGGG TCTATJTATC TCCAAATGGG AGATGAACAA CCAGAGTAGC ATCCAGGAAT ACACCTGCAC TGGGGACTGA AGAGGGGGTC 40 CTGGGTCTTG TCAAC'I=CA GGAGAGGGAA GAC'IMGGGC TGAAAGAcY-r TAGTCTGTGT TTFGAATAGTT CCTTGAGCCT CAGTCACTGA GCTAAGCTCC CTT1CGGAGGA AAAGGAGGTC CTGTCCGAAG GTCCCTCTTG 'ITGCAGTAGC ACCCCTCACC CCTACCCAAC TCAAGACACA CGGCTCACTr 117CAGGGCCC CACCCAGTCT CAGGGCCACT TCCTCTATGG CCTITCAAG AACACTGGCT CTAGTTCTCA GGGTCCTGAA. CCCATCATT TATGGGAGCA GAGAACAGGT CTACATAAGA CCCCCACTI17 CCCGTITAA CTGATATCTC CTGCTTCAGG 45 GGCTGGCCCT CATGCAGGGT TCCCTGAATT AGGAAGTGTG AACCCTGTCC CCTGAGTCCT CCCTGGCCTG TTCAGTCCCC AGCAATT1CCA GGGGTCGTAG AANL17GTGTC TGT17CCTGA GAAAGCTCT TCATGAGTTA AGCCTGAGCC CTCAAATGCC ACAAGTGGCC CATGAAAAGG GAGATGGGTA GAGTCCGGCN ACCCAGTGAC AGAGMrAGT CCTCITCT CAGAATGAGC TCACCTCAGA AGAAACCCCA AGCCATCACT GTCGCCTCCT TTTCCT'TCCT TCTTCCTCAC AGCAGGTCTA TAACAGTCAC CC= GGAGCC CATAACATAA CAGAGGAAGA 50 AGACACATGG CAGAAGCTTG AGGT7ATAAA GCAAT7CCGT CATCCAAAAT ATAACAC'ITC TACTCTTCAC CACGATATCA TGTTACTAAA GGTGACAACA CCTCTCTTCT CCCTITCCAC TTCCCATTCT CCTAAGCTTC TCCTTCAGGT CCTCATTGCC CTGAATITVT CTTAGGACTT GGCTATAACA TGAAGCTACT CACCCTGTCC CTCCCTGATC ACCTCCAACT GTCCAGAGCC CA ITCGAGG ACTGACAGTC C'rrCATrCCC TTCACAGF7G AAGGAGAAAG CCAGCCTGAC CCTGGCTGTG GGGACACTCC CCTTCCCATC ACAATTCAAC TI17GTCCCAC 55 CTGGGAGAAT GTGCCGGGTG GCTGGCTGGG GAAGAACAGG TGTGTTGAAG CCGGGCTCAG ACACTCTGCA AGAGGTGAAG CTGAGACTCA TGGATCCCCA GGCCTGCAGC CACTICAGAG AC'ITTG.ACCA CAATCTTCAG CTGTGTGTGG GCAATCCCAG GAAGACAAAA TCTGCATrA AGGTGATCCT CCAACTAGGT YITCCTCTCCA AAACTCACTG TI'CAGGGACC TGAATGCTCT TAGAAGGAGA TGGGGTCAGC AGGTTGTCAG TCAGGTGACA GGGTGAGCAT CACAGGAATT1 GCTGTCCTCC CGTGGTCCAA. GACAGCCTCT GACCATCCAT TCCAGTCTAC 60 TGCACTGGGG GCATGGGGTG ACTGTGGAGA ATGTGGATGA CGGTCCCAAG AAAGGAAGAA GGGGCATCAG AACTAGATGT ATAAGTGAGG AGCTCCACCT CCTGGGTCTG ACTTAGGTC TCACTGTGAC TCCAAGCTGG CTGGCAGACA GGAGTGGAGG ACTL1CCCGGG CTCACC'ITCT TCTCTCTCTC CTCCCCCTAC AGGGAGACTC TGGGGGCCCT VI17CTGTGTG CTGGGGTGGC CCAGGGCATC GTATCCTATG GACGGTCGGA TGCAAAGCCC CCTGCTGTCT TCACCCGAAT CTCCCATTAC CGGCCC TGGA TCAACCAGAT CCTGCAGGCA AATTAATCCT 65 GGATCCTGAG CCAGCCTGAA GGGAAGCTGG AACTGGACCT TAGCAGCAAA GTGTGTGCAA CTCATTCTGG FrTCTACCCTT GGT-1CCCTCA GCCACAACCC TAAGCCTCCA AGAGGTCTCC TACAGGTAAC AGAAC'TCA WO 00/62736 PCT/USOO/08020 248 ATAAACTTCA GTGAAGACAC AGCTTCTAGT CGTGAGTGTG TGTCCCTCTC TGCTGCTCTC TJCTCCTGCA CATGTGACCT GA'ITCCCAGC CCAAGCACCA AGGA ATCATCGGGG GCACAGAATC CAAGCCACAT TCCCGCCCCT ACATGGCCTA CCTGGAAATT GTAAC'ITCCA ACGGTCCCTC AAAA'V=GT GGTGGTI1TCC TI'ATAAGACG GAAC'I=GTG CTGACGGCTG CTCATTGTGC AGGAAGGTCT ATAACAGTCA CCCTrGGAGC 5 CCATAACATA ACAGAGGAAG AAGACACATG GCAGAAGC'IT GAGG'ITATAA AGCAATTCCG TCATCCAAAA TATAACAC'IT CTACTC I1CA CCACGATATC ATGTTACTAA AGTTGAAGGA GAAAGCCAGC CTGACCCTGG CTGTGGGGAC ACTCCCCTTC CCATCACAAT TCAAC'ITGT CCCACCTGGG AGAATGTGCC GGGTGGCTGG CTGGGGAAGA ACAGGTGTGT TGAAGCCGGG CTCAGACACT CTGCAAGAGG TGAAGCTGAG ACTCATGGAT CCCCAGGCCT GCAGCCACTI' CAGAGAC'IT GACCACAATC ITrCAGCTGTG TGTGGGCAAT CCCAGGAAGA 10 CAAAATCTGC A T]TAAGGGA GACTCTGGGG GCCCTCTCT GTGTGCTGGG GTGGCCCAGG GCATCGTATC CTATGGACGG TCGGATGCAA AGCCCCCTGC TGTC'ITCACC CGAATCTCCC AYTACCGGCC CTGGATCAAC CAGATCCTGC AGGCAAATTA A-3' (FRAG. NO:1887) (SEQ. ID NO:3015) 5'-ATCATCGGGG GCACAGAATC CAAGCCACAT TCCCGCCCCT ACATGGCCTA CCTGGAAATT GTAACTTCCA ACGGTCCCTC AAAATITGT GGTGG'FrTCC TFATAAGACG GAACTIGTG CTGACGGCTG CTCAT7GTGC 15 AGGAAGGTCT ATAACAGTCA CCCTTGGAGC CCATAACATA ACAGAGGAAG AAGACACATG GCAGAAGCT7 GAGGTTATAA AGCAATrCCG TCATCCAAAA TATAACACTT CTACTCTTCA CCACGATATC ATGTTACTAA AGTTGAAGGA GAAAGCCAGC CTGACCCTGG CTGTGGGGAC ACTCCCCT7C CCATCACAAT TCAACMTGT CCCACCTGGG AGAATGTGCC GGGTGGCTGG CTGGGGAAGA ACAGGTGTGT TGAAGCCGGG CTCAGACACT CTGCAAGAGG TGAAGCTGAG ACTCATGGAT CCCCAGGCCT GCAGCCACTT CAGAGA='~ GACCACAATC 20 T-rCAGCTGTG TGTGGGCAAT CCCAGGAAGA CAAAATCTGC ATnTAAGGGA GACTCTGGGG GCCCTCTTCT GTGTGCTGGG GTGGCCCAGG GCATCGTATC CTATGGACGG TCGGATGCAA AGCCCCCTGC TGTCTTCACC CGAATCTCCC ATTACCGGCC CTGGATCAAC CAGATCCTGC AGGCAAATTA A-3'(FRAG.NO:)(SEQ.ID NO:2468) 5'-TCCCAGT7AA TACATAATCA ATATGCAATT TA'I7AATACA TCTCTCCATG TCCACTCCCC CTGTATCTTG CCATTCTTGA CCTGCATFTC CATCCTCCTT ACC'ITCCCTA GAGGCCAACT CATTI1CT GAAAAACCTG 25 GCATTCCCA GAAAAAAAAG TGAAGGGCTG GGAGCTGTCC G'FrGTCCTGA =hGCTCCCT CTGCC=TGC '1CCAAATGT GGYIGGAAAG AAGCACTATT GAAAAATCCC TAAACGCACC CCTGCAGGGT TGGCTCTACC CTGTAGCCAT GGACACATGC TGTTGATACC ACCTGCCTCA TGAGTCTCAC ATAA=~GCC C'TrCACACT ATCTACCCCA TCAGCCTTAC CAAAACCATA CCTGCATCCT GGGCAGCATC TGCCCTTrCAA GAGACTAAGG AATCTCCTTG CAACCAAGAA TGACTAGACC AATGAGACAC CCMTAAGGC CCCAGCACAA TATAGAAATC 30 CCACAATATG GTAATCCCAG TAAGGAGCTA TCAAGCCAT GCAGGACCAT CTAGAATACA ACTAGAGTAT AG'ITCCTC AATCCAGGAA CTATACTCTA ACAGCTTGGC TCACAGGAAC CAGAAGTGAA GATGATGAGG ATCAGGGCTG AGCCTGTGAG CACCAGCTCC ACCACTGACA CCAACCACAG ATrAAACAAG CATCYFGTGG ACCCCTGGGA TGGAAAGAAT AGTrG'rGCC TI'ATCAACCT CCCCCACAGC CCACACAGAA AAGATAAAAT CATCATGGCT ACAGTGTITAC AGAAGATGAT GACCCAAGGA GTAGGCCTGC CTGAGTGAAT GCTGAGAGTG 35 ATAATGGGAG CAGTAGCATC TCAGAGACTA CAGCAGAAAC CATCCACATA AAGAGC'=G CCCAAACTITA TGATAAAGGG CACCCTCAGA GACTCTCCCT AC TI'AATAT TAGCCCATrG CAGAAATGGT GAGTGGAAAG AGAAATCTTA GGAAGAACCC CTTAAAAAAG CAAAATGCTT 'TrAGG IMG TGCTGAAGAG CCTGGAAAAG AAATAAGGAC ACACACGCTG AGAAATCTTC CTCCTGCCCC AACACTGGGA TAATCTCCAA GGATCTCTCC ATATCTCATT CTCCTGGATA CACTGTCCAC TCAGAAATAT TGTGCAGAGT GCAGTAATTC AAAAGTGAGC 40 TATrGTGT-rA GGAGTGAAGG CAAGAGTATC GTAAAATAAA TCAAA'TrTGA AATGAATrCT CTTAAATrGC TTATAGATG 'ITTAATGTAA GCCAGCAGCT ATTAAACGAT AAACCTrAAA TTCGAGAAAA ACTTGGTCAT TCAGAAACTA TAGAAACAGG CAGGACTTAT TGCGAGGGCA AACACAGAGT GAGCTCCAGC CTGCTTCAGG AAAATCTGCC AGTGCCATGA AGGATGTACT CTGTCTGCTC CACTGCACTA CTGCTCAGTA TGAGCCCATG CCATCAGCTG TCCCTGACCC ACAGGAGTTC TITAGAAGAG ACTGGTCAAC AAAAG'ITTCT AGGGTG=T1 45 ATACCTGCCA ACTCGAGGGT TAAAACAAGT TGCATAGAAA TGCTCAATCA AGAAAGACAC AGTCA'ITACT CAGAGAATAA TAAACAGCCT GGCAGCACAT GAATGAATAG AAAAAAGATG TTrACATGCAA AGCATGAAAT AACCAAATTC CATAACAGAT GTTAATCTGT AATGTGT~A GGAGAA'TrA GAGGAAGTAT AAGAT7TATr CMTCATCAA AAAAAYI7ATA GCCAATGAGG ATATATCTAT CAATI7ATCCA TCAAGTGGTG ATATGGCAGC ACAAGGTAAA ACACAAAGGA ATAAAACCAA CG TTATTAA GAACCAATCA TGTGGCATT CACATTGAGC 50 ATCATATTTA AT'TCTGAAAA AAATCC2FTGT ACTGTATCAT TCTFrcATATT TI'ATGGATGC AGTAACTAAG GCTGAGAACT TFAAAAT=T TCCTAAGTh'C AGACACATAG CTAAGTGGCA GAACCAAGAT TCAAACTCAC CCCATCTAAC TGCAGAGCAA ACTGCATGCC TTAAATGTCA AAGTGAATAC TAGCACAG Fr AATACAATGT ITrGGAAACTC AGAGAAGGAA TGATCCCTCT GCATrATAGT TACTAAGGAA TCA'FrGCCAT TATPTAAATG CCAGTGCTTC TACATCAGGC CCAAATTC TGTCCTACTA ACTGTGAATC AAGACT~rGAT TCAACCTCTA 55 CTTGAGTATC TGCCGCAATG AGAAATCACT TACCTCCACT AACCACACAT TTAT1TrATA ACAACAGATT GTTAGTAAGT CCTTTCTTAT ACATACTCAA CAGCTGCTrC CCAAGATGCT GTAGGATTAT GTCTAGAGTC AAACTAGCCA GAAGCAATGT CCAAAATACA CCATAACACT GTGCAGCAAA GGTCCTACTA CCACTTGYT GGCCCAAACA ITCTAGGCAG CACTGGATAT CTGAATCATC AATATrTCC ACAAACACTG ACCCCTCTAC CAGTCACCCT CACTAGAAGA ATTAAT17CCA CATGATAATA GCTCCCTCAT GTrACTCCCT TCTAAGTCAA 60 ATTGTACACC CC'TIATCTG ATTAACAGAG TCTAAGTCAC ATGACCTAAA TGCAAGAGAA CTGGGAATGG ACGTTTGTGG ATTCTACCT7 AGTAAGGCAA AGTTATCAT7 GGGAATTCCT CTAATACAGG AAGGGTG'ITC CAGAGACATT AAGGAGCCAT ATAAATGGAA AATGTCCACT ACAATCCATC ACTTGGTTrGC CCCACATCAA CATI'CATTCT T1'GCCACAC T-'AAAGMflC CAAGAACAAA AATTATCCCA CTGAACATAA TC'ITTACTAT CTITATATA AAGGAAAATT AGACTTGACT CAGCAGAACT GAAATAACCC AGCTCTAACA GTTACTGCTT 65 TT1AACTTCAA GTACTGTGTC TCTAGGTGAT ACCTGCTCCA ACAATAG TT GGTCACAT TCAA'ITTGAT ATTCTCTAGT CTCCCAACTT GATAACTGTA CCCTAAACCA TAAAGTTCAC TACCAACATG CTATATATAA WO 00/62736 PCT/USOO/08020 249 AATAACCAAA GGGGGAAGAA GAAAGAGAAA AAGGAAATCT CT7AAAATAC ACAGGTATAC ATATGACAAA GCAAAGAAGG AAATGTGAGC AGATAGTGCA GTCCTCGTrT CTGAAAT~rGG TCCCCTGACT GGGGCTATAC CTNL17CCAT7 TCCTCACCCT CAGCCAGGCA GGTGGAGCAA AAACTTAAGT CTTGGTGGAT CTGAATCTTG ATGCTGTGGA GCTGTCTAC TAGCCCCAGA CTACCTGCCT CTCAATFTCT AATTATATCA GTGAAAGCAA 5 ACAGC'TGA ITTGTAAG CCTCTGA'TTTGGTCTAA CTGATGTAAG ACCACAAGGA CAAGAGTrCT CCAGCTCCGG ATTCTCTrCT G'ITCTGTrAA TGGTGAAATG CCCGAGAGAA GAGTTGCCAA C'ITTGGCAAA TAAAAAATAC AGGATI1CCAG TTAAATTCAA ATI1?AGATAA ACAACAA'ITT 1TAGTAFTA GTGTGTCCCA TrCAATATTT GGACATACTT AACTAAAAAA TGATTTGTTG TTCATCTGAA ATACAAA'rfr AACTGGGCAT TCTGAATATT CTCTGGCAAC CCCCGAGAGA GTGAAGAAAG TGGTACAAGG ACACTTAAGA AGACCAGATr 10 TGAAAAGACA TTACGGATGT GInrAAATGT C FTATrCTAG AGAGAGTI'AG AGCTGTAGGT AGAACTTGGG AAAT7AAGTYr AAAAGCAGAC ACAGAGACCT GGCCAATATA TACTAAGGAG TGGATCACTC TGGTCACAAG CCCAACCTGA GACCAAGGGC ATAGTGAGAT GATTTGGGAA AGGCAC'ITAT ACACTACTCA TCCCCGTCTT TGAACTAAAT GCCTTATAAA TCTCCAAGAG AAATGACAGT CCACCATGTG GACTGCTrC TGTAAGTCCA GGGAAAATAA AAGCTATGTG CTI'GAAACCC ACTrCTGATA TI'ATAAGGTG TGTGATC'ITT GTCATGTTAA 15 TGGGTCTGAG TATCAA'ITCT ACAATT1GTAA AGTGACAGTA ATGGTGTGTC CCCAGGTrGT TGTGGAAAGC TTGATTCTTA ATGCAACAGT AGGAAACCCC AGCCTCTCTG GAGCAAACAC C=TCTACAT CTTTACTITCC CCTGCACATT GGCAGGACTC TATTCCTCTA 'T1'CTCTCTA GTGCTAGAGC AGAAAGGGAC CTrGATTrGA TATCAGGAAA ATCTATTTCT GAACCATAAG CTATGATAGC TGA1TTAAAA AA FTGACTAT CATGACATGA TAATGATCAT AATGGTAATA CATATI1GATA GGGTTGCCGT GAAAGTAATA ATATATCTAA GAGTTGTGAC 20 AATATATGAT ACGCCTAGAC TCTCAGAAAA TGCTAATTrCC AATCCCAATr GCTCTTTGCA TAAAGTTCTG TCCTAGGGTC TGTTCT'TrC CCACATCTAC CCTCCTTGGA TCTCTC'FrCT GTCTTTCA TGTGGTTCAG AGGAGGAGAG AGATCCAGGT CAATG2TTT CAAATTACAA GGAATTATCA ITT1AAATGGG GAAGAAGCTC AAGTTTTGAC GTGTAGTGGA ATTGGAGTGG AGTGGAGTGG AATGGAAACT AACAGGAAGA CACTGCACAT GGTTAAGATA AAGATrG'1TT CCTGAAACCT TTAA ITGTG CTACATACT CACACATACA TATGTGCATG 25 CACTGGGACT CTGCAATATG CATITCTGAC TATGGAACAT AGCCATAAAA GTC ITTGCAC TGAACG'ITCA GTGGGCCTm? CACAAGCTGC CCTAATT1GGG AAAGAAAAAC ATGGTCCCTC CAITCCTGC CCCCAACTCC AGAAAAGTCA CCATAGTTGA GGGTACATCT GAGAAGCCAG CACTGGGAG TTCAGGGCTC AAGTTCCTTT CTAGAAAAAC ACTGGGTGAT TCTAGGGGAA CTTCCGATCA GAAACAGCCA ATTCAGAGTG AGAGAAGAAA ACGTGACCAT GCAGTTCCTG TGGT~rACCAG CCTrGCCCCT CTCTTGCCTT CTGGGAGTTA TAAAACCCAA 30 GACTGGAAAG GAAAACCAGC ATIT7GCTCAG GCAGCCTCTC TGGGAAGATG CTGCTCT=C CTCTCCCCCT GCTGCTC'IM CTCTTGTGCT CCAGAGCTGA AGCTGGTGAG TATCAGGGTT CTTCCCTCTG AAATCTGCAG TATCAGCTCC TGAAACAAAG ATGTTFAGTC TGAAATAGCT GACTCCTAAA CAGGGTfCCA AGATCTCTCT TCAAGAGTCC CACAGAGGAA A T-CCACTT GGGATGTGTG CCACCCCACC CCCACCCCCA CCCACTGCCA TTCTCTACAG CCTAGGACAC CCCCAGGAAC AAGGAATITC ACCTCAATrG TAGAAAAGCC CAGAGCAAGT 35 GGAAGGAAAA GGGGTATCCC CAGGAAAACA GACATGTCCT CTTAATCTrC TGAGCATCAG GGCTACCCAT TACTTTGTGA CTTCTCACT CTGTGACCAT GCTCAAGAGC TATGGAGAAA TCTAAAACAG GAACCTGGAC AGTGGGTCCT ACACAGAGAC AGAGGAGAGT GGGCCAGGGC AAGGTGGGAG TGGGAGAAGT CTGAGATGAA AACATCAGAA TGGAGCAGAG GCAAGAATGA GA ITCACCT GGGAGGTTAT GGGTGGGGAA AGATACGAAA TACAGGAGAC AGGAGAGGGA AGATGGGCGG AACACAGGGT GAGAATGAGA TICCAGGGAA GCCTAGCTCA 40 GCTI17AACCC AATI17GTCCA T7CAT17GGAG AGAGTATCTA TGGCCGTGT7 CAAACCCTGG GGTGCTCTGT TCCAGGGGAG ATCATCGGGG GCACAGAATG CAAGCCACAT TCCCGCCCCT ACATGGCCTA CCTGGAAATT GTAACY'TCCA ACGGTCCCTC AAAATITGT GGTGGTCC TTATAAGACG GAACTTTGTG CTGACGGCTG CTCATGTGC AGGAAGGTGA GACAACAGGG TCTA I=ATC TCCAAATGGG AGATGAACAA CCAGAGTAGC ATCCAGGAAT ACACCTGCAC TGGGGACTGA AGAGGGGGTC CTGGGTCTG TCAACTrCA GGAGAGGGAA 45 GACTTTGGGC TGAAAGACTT TAGTCTGTGT TTGAATAGT-F CCTTGAGCCT CAGTCACTGA GCTAAGCTCC CTTCGGAGGA AAAGGAGGTC CTGTCCGAAG GTCCCTCTTG 'ITGCAGTAGC ACCCCTCACC CCTACCCAAC TCAAGACACA CGGCTCACT7 TTCAGGGCCC CACCCAGTCT CAGGGCCACT TCCTCTATGG CCTTICAAG AACACTGGCT CTAGTTCTCA GGGTCCTGAA CCCATCA=T TATGGGAGCA GAGAACAGGT CTACATAAGA CCCCCACTTT CCCGTITI7AA CTGATATCTC CTGCITFCAGG GGCTGGCCCT CATGCAGGGT TCCCTGAATr 50 AGGAAGTGTG AACCCTGTCC CCTGAGTCCT CCCTGGCCTG TTrCAGTCCCC AGCAATTCCA GGGGTCGTAG AAATTGTGTC TG TrCCTGA GAAAGCTCTT TCATGAGTTA AGCCTGAGCC CTCAAATGCC ACAAGTGGCC CATGAAAAGG GAGATGGGTA GAGTCCGGCN ACCCAGTGAC AGAGTITAGT CCTC'1ICT CAGAATGAGC TCACCTCAGA AGAAACCCCA AGCCATCACT GTCGCCTCCT 1CCTrCCT TCTCCTCAC AGCAGGTCTA TAACAGTCAC CCTTGGAGCC CATAACATAA CAGAGGAAGA AGACACATGG CAGAAGCT'FG AGG'ITATAAA 55 GCAArrCCGT CATCCAAAAT ATAACACT7C TACTCTTCAC CACGATATCA TGT7ACTAAA GGTGACAACA CCTCTC'CT CCCTTTCCAC TT1CCCATTCT CCTAAGC'ITC TCC'I17CAGGT CCTCATTGCC CTGAA'TTT CTTAGGACTT GGCTATAACA TGAAGCTACT CACCCTGTCC CTCCCTGATC ACCTCCAACT GTCCAGAGCC CA'ITCGAGG ACTGACAGTC C'TrCA TCCC TfCACAGTTG AAGGAGAAAG CCAGCCTGAC CCTGGCTGTG GGGACACTCC CCTTCCCATC ACAATTCAAC TTTGTCCCAC CTGGGAGAAT GTGCCGGGTG GCTGGCTGGG 60 GAAGAACAGG TGTGTI'GAAG CCGGGCTCAG ACACTCTGCA AGAGGTGAAG CTGAGACTCA TGGATCCCCA GGCCTGCAGC CAC'ITCAGAG ACnI7GACCA CAATCTTCAG CTGTGTGTGG GCAATCCCAG GAAGACAAAA TCTGCAYL1A AGGTGATCCT CCAACTAGGT TTCCTCTCCA AAACTCACTG 'ITCAGGGACC TGAATGCTCT TAGAAGGAGA TGGGGTCAGC AGGT7GTCAG TCAGGTGACA GGGTGAGCAT CACAGGAAITr GCTGTCCTCC CGTGGTCCAA GACAGCCTCT GACCATCCAT TCCAGTCTAC TGCACTGGGG GCATGGGGTG ACTGTGGAGA 65 ATGTGGATGA CGGTCCCAAG AAAGGAAGAA GGGGCATCAG AACTAGATGT ATAAGTGAGG AGCTCCACCT CCTGGGTCTG AC'TrTAGGTC TCACTGTGAC TCCAAGCTGG CTGGCAGACA GGAGTGGAGG ACTTCCCGGG WO 00/62736 PCT/USOO/08020 250 CTCACCTTCT TCTCTCTCTC CTCCCCCTAC AGGGAGACTC TGGGGGCCCT CTTCTGTGTG CTGGGGTGGC CCAGGGCATC GTATCCTATG GACGGTCGGA TGCAAAGCCC CCTGCTGTCT TCACCCGAAT CTCCCATTAC CGGCCCTGGA TCAACCAGAT CCTGCAGGCA AATTAATCCT GGATCCTGAG CCAGCCTGAA GGGAAGCTGG AACTGGACCT TAGCAGCAAA GTGTGTGCAA CTCATTCTGG TTCTACCCTT GGTTCCCTCA GCCACAACCC 5 TAAGCCTCCA AGAGGTCTCC TACAGGTAAC AGAACTCA ATAAACTTCA GTGAAGACAC AGCTTCTAGT CGTGAGTGTG TGTCCCTCTC TGCTGCTCTC TTCTCCTGCA CATGTGACCT GATTCCCAGC CCAAGCACCA AGGA-3' (FRAG. NO:) (SEQ. ID NO:2467) 5'-GGBGCBCBBG-3' (FRAG. NO:1888) (SEQ. ID NO:1901) 5'-GBBGCBGC-3' (FRAG. NO:1889) (SEQ. ID NO:1902) 10 5'-GGGGCBBGG CG-3' (FRAG. NO:1890) (SEQ. ID NO:1903) 5'-CGTTTTCTTCTCTC-3' (FRAG. NO:1369)(SEQ. ID NO:1378) 5'-GCTGGTTTTCCTTTCC-3' (FRAG. NO:1370)(SEQ. ID NO:1379) 5'-TGGCAGTGGGTGGGGGTGGGGGTGGGGTGGC-3' (FRAG. NO:1371)(SEQ. ID NO:1380) 5'-TTCCTTGTTCCTGGGGGTGTCCT-3' (FRAG. NO:1372)(SEQ. ID NO:1381) 15 5'-CTTGCTCTGGGCTTCT-3' (FRAG. NO:1373)(SEQ. ID NO:1382) 5'-CCCCTTTTCCTrCC-3' (FRAG. NO:1374)(SEQ. ID NO: 1383) [ 5'-TGTCTGTTTTCCTGGGG-3' (FRAG. NO: 1375)(SEQ. ID NO: 1384) 5'-CTCTCCTCTGTCTCTGTGT-3' (FRAG. NO: 1376)(SEQ. ID NO: 1385) 5'-CCTTGCCCTGGCCC-3' (FRAG. NO:1377)(SEQ. ID NO: 1386) 20 5'-TCTTCCCTCTCCTGTCTCCTGT-3' (FRAG. NO: 1378)(SEQ. ID NO: 1387) 5'-CCCTGTGTTCCGCCC-3' (FRAG. NO: 1379)(SEQ. ID NO: 1388) 5'-GTCTTCCCTCTCCTG-3' (FRAG. NO: 1380)(SEQ. ID NO: 1389) 5'-ACCTCCTTTTCCTCCG-3' (FRAG. NO: 1381)(SEQ. ID NO: 1390) 5'-CTGGGTGGGGCCCTG-3' (FRAG. NO:1382)(SEQ. ID NO:1391) 25 5'-CCTGTTCTCTGCTCCC-3' (FRAG. NO: 1383)(SEQ. ID NO: 1392) 5'-TGGCTTGGGGTTTCTTCTG-3' (FRAG. NO: 1384)(SEQ. ID NO:1393) 5'-TGTGTCTTCTTCCTCTGTT-3' (FRAG. NO: 1385)(SEQ. ID NO: 1394) 5'-GGCTGGCTTTCTCCTTC-3' (FRAG. NO:1386)(SEQ. ID NO:1395) 5'-TTTTGTCTTCCTGGG-3' (FRAG. NO: 1387)(SEQ. ID NO: 1396) [1397)] 30 5'-TGCCCCTTCTTCCTTCTrTGGG-3' (FRAG. NO: 1388)(SEQ. ID NO:1397) 5'-TCCTTGGTGCTTGGGCTGGG-3' (FRAG. NO: 1389)(SEQ. ID NO: 1398) 5'-GGBGCTGBTB CTGCBGATTT CBGBGGGBBG BBCCCTGBTB CTCBCCBGCT TCBGCTCTGG BGCBCBBGBG BBBGBGCBGC BGGGGGBGBG GBBGBBGCBG CBTCTTCCCB GBGBGGCTGC CTGBGCBBBT GCTGGTTTTC CTTTCCBGTC TTGGGTTTTB TBBCTCCCBG BBGGCBBGBG BGGGGCBBGG-3' (FRAG.NO:1891) (SEQ.ID 35 NO:1904) Endothelial Nitric Oxide Synthase Nucleic Acids and Antisense Oligonucleotide Fragments* 5'-GCGTCTTGGG GTGCBGGGCC CBTCCTGCTG CGCCTGGGCG CTGCTGTGCG TCCGTCTGCT GGGGGGCCGG GGTGGCTGGG CCCTGCTTGC CGCACGACCC CGGGCCGACC CGAGGCTCGG GGGGCTGTGT TCTGGCGCTG GTGGGCTTGG GCCCCTCTGG GGGCTGGGTT TCCTGCTGCG CCTGGGCGCT GGCGTCTTGG GGTGCGGGGC 40 CGGGGGGCCG GGGGGCCGCT GTTCGTGGGC CTGGGGGTGC CTGTGGCTGC CGGTTGCCCC GGTTGGTGGC GCCGTCCTGC TGCCGGTCGT TGGCTGGGTC CCCCCGCCCG TTTCCTGGGG TCCGCGTGGG GTGCTCCGGT TCCTCGTGCC GCTGCTGCCT TGTCTTTCCG GCCGTGGCGG CGTGGTGGTC CGCCCCCCCT GGCCTTCTGC TCGGGGTCTG GCTGGTTGCC GGTGCCCTTG GCGGCGGTCT TCTTCCTGGT GGCTCTGGGC CCGGCCGGTC TCGGGCGTCT CGTGTTCGCT CTTGTGCTGT TCCGGCCGCT CCTTCCTCTT CCGCCGCCGC CGCTCCCCGC 45 CCGCTCGTCG CCCTGGCCCG GCCTCCTCCT GGCCGCTGTC TCGGGCGGCG GCCTTGGCGC TCCGTTTGGG GCTGCCTCTG GCGCTTCCGG CCCTCGGCCT GGGCGCTCTC TTCCGCCTGT GCTGGTGGCC CTCGTGGGCC CCTCCTGGCC TCCGGTGTCC TGTGGTCCCC CGGCTGGTGG CCGGGCCGGT TGGGCGGGCG TGGGCGCCGG CGGGTCCTCC GGGCTGCCCT TCTCCGCCGG GGGTCCCGCG CTCCTGCTGT TCCCTGGGCT CTTCTGCCTC TCTCCTGGGT GGGTGCTGGG TGCCGGGGTC TCCGGGCTTG CCCCGCGCTG CTGGGCGTTC TGCGGTCTITG 50 GGGTTGTCTG TGGCCCCGCT CGTGTCGCCC TCCGTCGCCC GTCGCCGGCC TCGTCCCCTC CTGGGTGCGC GGCGGGCTGG TCCTGGCGTT TTfGCTCCTTC CTGGGCGTCT TGGGGTGCBG GGCCCBTCCT GCTGCGCCTG GGCGCTGCTG TGCGTCCGTC TGCTGGGGGG CCGGGGTGGC TGGGCCCTGC TTGCCGCACG ACCCCGGGCC GACCCGAGGC TCGGGGGGCT GTGTTCTGGC GCTGGTGGGC TTGGGCCCCT CTGGGGGCTG GGTTITCCTGC TGCGCCTGGG CGCTGGCGTC TTGGGGTGCG GGGCCGGGGG GCCGGGGGGC CGCTGTTCGT GGGCCTGGGG 55 GTGCCTGTGG CTGCCGGTTG CCCCGGTTGG TGGCGCCGTC CTGCTGCCGG TCGTTGGCTG GGTCCCCCCG CCCGTTTCCT GGGGTCCGCG TGGGGTGCTC CGGTTCCTCG TGCCGCTGCT GCCTTGTCTT TCCGGCCGTG GCGGCGTGGT GGTCCGCCCC CCCTGGCCTT CTGCTCGGGG TCTGGCTGGT TGCCGGTGCC CTTGGCGGCG GTCT'rCTTCC TGGTGGCTCT GGGCCCGGCC GGTCTCGGGC GTCTCGTGTT CGCTCTTGTG CTGTTCCGGC CGCTCCTTCC TCTTCCGCCG CCGCCGCTCC CCGCCCGCTC GTCGCCCTGG CCCGGCCTCC TCCTGGCCGC 60 TGTCTCGGGC GGCGGCCTTG GCGCTCCGTT TGGGGCTGCC TCTGGCGCTT CCGGCCCTCG GCCTGGGCGC TCTCTTCCGC CTGTGCTGGT GGCCCTCGTG GGCCCCTCCT GGCCTCCGGT GTCCTGTGGT CCCCCGGCTG GTGGCCGGGC CGGTFGGGCG GGCGTGGGCG CCGGCGGGTC CTCCGGGCTG CCCTTCTCCG CCGGGGGTCC CGCGCTCCTG CTGTTCCCTG GGCTCTTCTG CCTCTCTCCT GGGTGGGTGC TGGGTGCCGG GGTCTCCGGG CTTGCCCCGC GCTGCTGGGC GTTCTGCGGT CTT1GGGGTTG TCTGTGGCCC CGCTCGTGTC GCCCTCCGTC 65 GCCCGTCGCC GGCCTCGTCC CCTCCTGGGT GCGCGGCGGG CTGGTCCTGG CGTTGCTC CTTCCTGG-3' (FRAG. NO:1892) (SEQ. ID NO: 1905) WO 00/62736 PCT/USOO/08020 251 5-GCGGGGCCG-3' FRAGG. NO:1893) (SEQ. ID NO: 1906) 5'-CGGGGGGC-3' (FRAG. NO:1894) (SEQ. ID NO: 1907) 5'-GCCGGCGGGC-3' (FRAG. NO:1895) (SEQ. ID NO: 1908) 5'-CTGTGCGTCCGTCTGCTGG FRAGG. NO:1390)(SEQ. ID NO:1399) 5 GGGGCCGGGGTGGCTGGGCCCTGCTTGCCGC FRAGG. NO: 1391)(SEQ. ID NO: 1400) ACGACCCCGGGCCGACCCGAG (FRAG. NO:1392)(SEQ. ID NO:1401) GCTCGGGGGGCTGTGTTCTGGCGCTGGTGGG FRAGG. NO: 1393)(SEQ. ID NO: 1402) CTTGGGCCCCTCTGGGGGCTGGGTT (FRAG. NO: 1394)(SEQ. ID NO: 1403) TCCTGCTGCGCCTGGGCGCTG FRAGG. NO:1395)(SEQ. ID NO:1404) 10 GCGTCTTGGGGTGC FRAGG. NO:1396)(SEQ. ID NO: 1405) GGGGCCGGGGGGCCGGGGG (FRAG. NO: 1397)(SEQ. ID NO: 1406) GCCGCTGTTCGTGGGCCTGGG (FRAG. NO: 1398)(SEQ. ID NO: 1407) GGTGCCTGTGGCTGCC (FRAG. NO:1399)(SEQ. ID NO: 1408) GGTTGCCCCGGTTGGTGGC (FRAG. NO: 1400)(SEQ. ID NO: 1409) 15 GCCGTCCTGCTGCCGGT FRAGG. NO: 1401)(SEQ. ID NO:1410) CGTTGGCTGGGTCCCCCCGC (FRAG. NO: 1402)(SEQ. ID NO: 1411) CCGTTTCCTGGGGTCC FRAGG. NO:1403)(SEQ. ID NO:1412) GCGTGGGGTGCTCC (FRAG. NO: 1404)(SEQ. ID NO: 1413) GGTTCCTCGTGCCG FRAGG. NO: 1405)(SEQ. ID NO:1414) 20 CTGCTGCCTTGTCTTTCC FRAGG. NO:1406)(SEQ. ID NO:1415) GGCCGTGGCGGCGTGGTGGTCC FRAGG. NO: 1407)(SEQ. ID NO: 1416) GCCCCCCCTGGCCTTCTGCTC FRAGG. NO:1408)(SEQ. ID NO:1417) GGGGTCTGGCTGGT (FRAG. NO:1409)(SEQ. ID NO: 1418) TGCCGGTGCCCTTGGCGGC FRAGG. NO:1410)(SEQ. ID NO: 1419) 25 GGTCTTCTTCCTGGTG (FRAG. NO:1411)(SEQ. ID NO:1420) GCTCTGGGCCCGGCCGGTCTCGG (FRAG. NO: 1412)(SEQ. ID NO: 1421) GCGTCTCGTGTTCG FRAGG. NO: 1413)(SEQ. ID NO: 1422) CTCTTGTGCTGTTCCGGCCG FRAGG. NO: 1414)(SEQ. ID NO: 1423) CTCCTTCCTCTTCCGCCGCC FRAGG. NO: 1415)(SEQ. ID NO: 1424) 30 GCCGCTCCCCGCCC FRAGG. NO: 1416)(SEQ. ID NO: 1425) GCTCGTCGCCCTGGCCC FRAGG. NO: 1417)(SEQ. ID NO: 1426) GGCCTCCTCCTGGCCGC FRAGG. NO: 1418)(SEQ. ID NO: 1427) TGTCTCGGGCGGCGGCCT'GGC FRAGG. NO: 1419)(SEQ. ID NO: 1428) GCTCCGTTTGGGGCTG FRAGG. NO: 1420)(SEQ. ID NO: 1429) 35 CCTCTGGCGCTTCC (FRAG. NO:1421)(SEQ. ID NO: 1430) GGCCCTCGGCCTGGGCGCTC FRAGG. NO: 1422)(SEQ. ID NO: 1431) TCTTCCGCCTGTGC FRAGG. NO: 1423)(SEQ. ID NO: 1432) TGGTGGCCCTCGTGG FRAGG. NO: 1424)(SEQ. ID NO: 1433) GCCCCTCCTGGCCTCCGGTGTCC FRAGG. NO: 1425)(SEQ. ID NO: 1434) 40 TGTGGTCCCCCGGCTGGT FRAGG. NO: 1426)(SEQ. ID NO: 1435) GGCCGGGCCGGTTGGGCGGGC FRAGG. NO: 1427)(SEQ. ID NO: 1436) GTGGGCGCCGGCGGGTCCTCC FRAGG. NO: 1428)(SEQ. ID NO: 1437) GGGCTGCCCTTCTCC FRAGG. NO: 1429)(SEQ. ID NO: 1438) GCCGGGGGTCCCGC FRAGG. NO: 1430)(SEQ. ID NO: 1439) 45 GCTCCTGCTGTTCCCTGGGCTCTTCTGCC FRAGG. NO:1431)(SEQ. ID NO:1440) TCTCTCCTGGGTGGGTGCTGGGTGCCG FRAGG. NO: 1432)(SEQ. ID NO: 1441) GGGTCTCCGGGCTTG FRAGG. NO: 1433)(SEQ. ID NO:1442) CCCCGCGCTGCTGGGCGTTCTGC FRAGG. NO: 1434)(SEQ. ID NO: 1443) GGTCTTGGGGTTGTC FRAGG. NO: 1435)(SEQ. ID NO:1444) 50 TGTGGCCCCGCTCG FRAGG. NO: 1436)(SEQ. ID NO: 1445) TGTCGCCCTCCGTCGCC FRAGG. NO: 1437)(SEQ. ID NO: 1446) CGTCGCCGGCCTCGTCC FRAGG. NO:1438)(SEQ. ID NO:1447) CCTCCTGGGTGCGC FRAGG. NO: 1439)(SEQ. ID NO:1448) GGCGGGCTGGTCCT FRAGG. NO: 1440)(SEQ. ID NO: 1449) 55 GGCGTTTTrGCTCCTTrCCTGG (FRAG. NO: 1441)(SEQ. ID NO: 1450) 5'-GCGTCTTGGGGTGCBGGGCCCBTCCTGCTGCGCCTGGGCGCTG-3'(FRAG. NO:1896) (SEQ. ID NO: 1909) Inducible Nitric Oxide Synthase Nucleic Acids and Antisense Oligonucleotide Fragments 5'-CTGCCCCBGT TTTTGBTCCT CBCBTGCCGT GGGGBGGBCB BTGGCTGCCT CCCCGGGGTT TCTGCTGCTT GCTGCTTCTT TCCCGTCTCC CTTCTTTCCC GTCTCCTT TGCCTCTTTG GGTTCCTGTT GTTTCTGGCC 60 TGCTTGGTGG CGGCTTGTGC GTTTCCTCTC TCTTCTCTTG GGTCTCCGCT TCTCGTCCTG CCTTTTCCTG TCTCTGTCGC GCCGTTCCTC CTCCGGCGTC CTCCTGCCCT GTGCTGTTTG CCTCGGGTGG TGCGGGTCCC GGTGCTCCCC CGGCGGGCCG GCTGGTTGCC TGGGCCTGTC TGGTGGGGTG TGGGGCCGCT GGGTTGGGGG TUTGGTGGGC TCTTCTGTGG CCTGTGGGGC TGTTGGTGTC TCTGTGGGCG TGTGCTGGGT CTTGGGGCTT CCTCCCTTGT GCTGGGTGCG GCCTCCCCGC CCCCCTTCTG GGCCGGTGGC CTGGCTCCT GTGGGCGCTT 65 CTGGCTCTTG CCCTGTCCTT CTTCGCCTCG TGGCTGCTGG GCTGC CATATGTATG GGAATACTGT ATTTCAGGCA TTATAAGGAA TGAAATTATA GGCCGGGCAT TGTGGCTAAC CCTTGTAATC CTAGCACTTT WO 00/62736 PCT/USOO/08020 252 GAGAGGCTGA AGTGGGCAGA TCACTTGAGC TTCAGAGTTC GAGACCAGCA TGGACAACAT GGTGAAACCC AGTCTCTACC AAAAACACAA AAATATTAGC TGGGTGTGGT GGTGCATGCC TGTAGTCCCA GCTACTCAGG AGGCTGAGGT GGGAGGATCG CTTGAGCCTG GGAGGCAGAA GTTGCAATGA GCAGAGATCG TGCCACTCCG CTCCAGTCTT GGTGACAGAA TGAGACTCCA TCTCAAAAAT AAATAAATAA ATAAATAAAA TAAATGAAAT 5 GAAATTATAA GAAATTACCA CTTTTTCATG TAAGAAGTGA TCATTTCCAT TATAAGGGAA GGAATTTAAT CCTACCTGCC ATTCCACCAA AGCTTACCTA GTGCTAAAGG ATGAGGTGTT AGTAAGACCA ACATCTCAGA GGCCTCTCTG TGCCAATAGC CTrCCTTCCT TTCCCTrCCA AAAACCTCAA GTGACTAGTT CAGAGGCCTG TCTGGAATAA TGGCATCATC TAATATCACT GGCCTTCTGG AACCTGGGCA TTTTCCAGTG TGTTCCATAC TGTCAATATT CCCCCAGCTT CCTGGACTCC TGTCACAAGC TGGAAAAGTG AGAGGATGGA CAGGGATTAA 10 CCAGAGAGCT CCCTGCTGAG GAAAAAATCT CCCAGATGCT GAAAGTGAGG CCATGTGGCT TGGCCAAATA AAACCTGGCT CCGTGGTGCC TCTGTCTTAG CAGCCACCCT GCTGATGAAC TGCCACCTTG GACTTGGGAC CAGAAAGAGG TGGGTTGGGT GAAGAGGCAC CACACAGAGT GATGTAACAG CAAGATCAGG TCACCCACAG GCCCTGGCAG TCACAGTCAT AAATTAGCTA ACTGTACACA AGCTGGGGAC ACTCCCTTTG GAAACCAAAA AAAAAAAAAA AAAAAAGAGA CCTTTATGCA AAAACAACTC TCTGGATGGC ATGGGGTGAG TATAAATACT 15 TCTTGGCTGC CAGTGTGTTC ATAACTTTGT' AGCGAGTCGA AAACTGAGGC TCCGGCCGCA GAGAACTCAG CCTCATTCCT GCTTTAAAAT CTCTCGGCCA CCTTTGATGA GGGGACTGGG CAGTFCTAGA CAGTCCCGAA GTTCTCAAGG CACAGGTCTC TTCCTGGTTT GACTGTCCTT ACCCCGGGGA GGCAGTGCAG CCAGCTGCAA GGTGAGTTGC C CATATGTATG GGAATACTGT ATTTCAGGCA TTATAAGGAA TGAAATTATA GGCCGGGCAT TGTGGCTAAC CCTTGTAATC CTAGCACTTT GAGAGGCTGA AGTGGGCAGA TCACTTGAGC TTCAGAGTrC 20 GAGACCAGCA TGGACAACAT GGTGAAACCC AGTCTCTACC AAAAACACAA AAATATTAGC TGGGTGTGGT GGTGCATGCC TGTAGTCCCA GCTACTCAGG AGGCTGAGGT GGGAGGATCG CTTGAGCCTG GGAGGCAGAA GT'TGCAATGA GCAGAGATCG TGCCACTCCG CTCCAGTCTT GGTGACAGAA TGAGACTCCA TCTCAAAAAT AAATAAATAA ATAAATAAAA TAAATGAAAT GAAATTATAA GAAATTACCA CTTTCATG TAAGAAGTGA TCATTCCAT TATAAGGGAA GGAATITAAT CCTACCTGCC ATTCCACCAA AGCTTACCTA GTGCTAAAGG 25 ATGAGGTGTT AGTAAGACCA ACATCTCAGA GGCCTCTCTG TGCCAATAGC CTTCCTTCCT TTCCCTTCCA AAAACCTCAA GTGACTAGTT CAGAGGCCTG TCTGGAATAA TGGCATCATC TAATATCACT GGCCTTCTGG AACCTGGGCA TTTCCAGTG TGTTCCATAC TGTCAATATT CCCCCAGCTT CCTGGACTCC TGTCACAAGC TGGAAAAGTG AGAGGATGGA CAGGGATTAA CCAGAGAGCT CCCTGCTGAG GAAAAAATCT CCCAGATGCT GAAAGTGAGG CCATGTGGCT TGGCCAAATA AAACCTGGCT CCGTGGTGCC TCTGTCTrAG CAGCCACCCT 30 GCTGATGAAC TGCCACCTTG GACTTGGGAC CAGAAAGAGG TGGGTTGGGT GAAGAGGCAC CACACAGAGT GATGTAACAG CAAGATCAGG TCACCCACAG GCCCTGGCAG TCACAGTCAT AAATTAGCTA ACTGTACACA AGCTGGGGAC ACTCCCTG GAAACCAAAA AAAAAAAAAA AAAAAAGAGA CCTTTATGCA AAAACAACTC TCTGGATGGC ATGGGGTGAG TATAAATACT TCTTGGCTGC CAGTGTGTTC ATAACTTTGT AGCGAGTCGA AAACTGAGGC TCCGGCCGCA GAGAACTCAG CCTCATTCCT GCTTTAAAAT CTCTCGGCCA CCTTTGATGA 35 GGGGACTGGG CAGTTCTAGA CAGTCCCGAA GTrCTCAAGG CACAGGTCTC TTCCTGGTTT GACTGTCCTT ACCCCGGGGA GGCAGTGCAG CCAGCTGCAA GGTGAGTTGC C-3' (FRAG. NO:_)(SEQ. ID NO: 3016) 5'-CTGCTTTAAA ATCTCTCGGC CACC'TTGAT GAGGGGACTG GGCAGTTCTA GACAGTCCCG AAGTTCTCAA GGCACAGGTC TCTTCCTGGT TTGACTGTCC TTACCCCGGG GAGGCAGTGC AGCCAGCTGC AAGCCCCACA GTGAAGAACA TCTGAGCTCA AATCCAGATA AGTGACATAA GTGACCTGCT TTGTAAAGCC ATAGAGATGG 40 CCTGTCCTTG GAAATTTCTG TTCAAGACCA AATTCCACCA GTATGCAATG AATGGGGAAA AAGACATCAA CAACAATGTG GAGAAAGCCC CCTGTGCCAC CTCCAGTCCA GTGACACAGG ATGACCTTCA GTATCACAAC CTCAGCAAGC AGCAGAATGA GTCCCCGCAG CCCCTCGTGG AGACGGGAAA GAAGTCTCCA GAATCTCTGG TCAAGCTGGA TGCAACCCCA TTGTCCTCCC CACGGCATGT GAGGATCAAA AACTGGGGCA GCGGGATGAC TTTCCAAGAC ACACTTCACC ATAAGGCCAA AGGGATTTA ACTTGCAGGT CCAAATCTTG CCTGGGGTCC 45 AT7ATGACTC CCAAAAGTTT GACCAGAGGA CCCAGGGACA AGCCTACCCC TCCAGATGAG CTTCTACCTC AAGCTATCGA ATTTGTCAAC CAATATTACG GCTCCTrCAA AGAGGCAAAA ATAGAGGAAC ATCTGGCCAG GGTGGAAGCG GTAACAAAGG AGATAGAAAC AACAGGAACC TACCAACTGA CGGGAGATGA GCTCATCTITC GCCACCAAGC AGGCCTGGCG CAATGCCCCA CGCTGCATTG GGAGGATCCA GTGGTCCAAC CTGCAGGTCT TCGATGCCCG CAGCTGTTCC ACTGCCCGGG AAATGTTTGA ACACATCTGC AGACACGTGC GTTACTCCAC 50 CAACAATGGC AACATCAGGT CGGCCATCAC CGTGTTCCCC CAGCGGAGTG ATGGCAAGCA CGACTTCCGG GTGTGGAATG CTCAGCTCAT CCGCTATGCT GGCTACCAGA TGCCAGATGG CAGCATCAGA GGGGACCCTG CCAACGTGGA ATTCACTCAG CTGTGCATCG ACCTGGGCTG GAAGCCCAAG TACGGCCGCT TCGATGTGGT CCCCCTGGTC CTGCAGGCCA ATGGCCGTGA CCCTGAGCTC TTCGAAATCC CACCTGACCT TGTGCTTGAG GTGGCCATGG AACATCCCAA ATACGAGTGG TTTCGGGAAC TGGAGCTAAA GTGGTACGCC CTGCCTGCAG 55 TGGCCAACAT GCTGCTTGAG GTGGGCGGCC TGGAGTTCCC AGGGTGCCCC TTCAATGGCT GGTACATGGG CACAGAGATC GGAGTCCGGG ACTTCTGTGA CGTCCAGCGC TACAACATCC TGGAGGAAGT GGGCAGGAGA ATGGGCCTGG AAACGCACAA GCTGGCCTCG CTCTGGAAAG ACCAGGCTGT CGTTGAGATC AACATTGCTG TGATCCATAG TTTTCAGAAG CAGAATGTGA CCATCATGGA CCACCACTCG GCTGCAGAAT CCTTCATGAA GTACATGCAG AATGAATACC GGTCCCGTGG GGGCTGCCCG GCAGACTGGA TTTGGCTGGT CCCTCCCATG 60 TCTGGGAGCA TCACCCCCGT GTTTCACCAG GAGATGCTGA ACTACGTCCT GTCCCCTTTC TACTACTATC AGGTAGAGGC CTGGAAAACC CATGTCTGGC AGGACGAGAA GCGGAGACCC AAGAGAAGAG AGATTCCATT GAAAGTCTTG GTCAAAGCTG TGCTCTTTGC CTGTATGCTG ATGCGCAAGA CAATGGCGTC CCGAGTCAGA GTCACCATCC TCTTTGCGAC AGAGACAGGA AAATCAGAGG CGCTGGCCTG GGACCTGGGG GCCTTATTCA GCTGTGCCTT CAACCCCAAG GTTGTCTGCA TGGATAAGTA CAGGCTGAGC TGCCTGGAGG AGGAACGGCT 65 GCTGTTGGTG GTGACCAGTA CGTTTGGCAA TGGAGACTGC CCTGGCAATG GAGAGAAACT GAAGAAATCG CTCTTCATGC TGAAAGAGCT CAACAACAAA TTCAGGTACG CTGTGTTTGG CCTCGGCTCC AGCATGTACC WO 00/62736 PCT/USOO/08020 253 CTCGGTTCTG CGCCTTTGCT CATGACATTG ATCAGAAGCT GTCCCACCTG GGGGCCTCTC AGCTCACCCC GATGGGAGAA GGGGATGAGC TCAGTGGGCA GGAGGACGCC TTCCGCAGCT GGGCCGTGCA AACCTTCAAG GCAGCCTGTG AGACGTTTGA TGTCCGAGGC AAACAGCACA TTCAGATCCC CAAGCTCTAC ACCTCCAATG TGACCTGGGA CCCGCACCAC TACAGGCTCG TGCAGGACTC ACAGCCTG GACCTCAGCA AAGCCCTCAG 5 CAGCATGCAT GCCAAGAACG TGTTCACCAT GAGGCTCAAA TCTCGGCAGA ATCTACAAAG TCCGACATCC AGCCGTGCCA CCATCCTGGT GGAACTCTCC TGTGAGGATG GCCAAGGCCT GAACTACCTG CCGGGGGAGC ACCTTGGGGT TTGCCCAGGC AACCAGCCGG CCCTGGTCCA AGGCATCCTG GAGCGAGTGG TGGATGGCCC CACACCCCAC CAGACAGTGC GCCTGGAGGA CCTGGATGAG AGTGGCAGCT ACTGGGTCAG TGACAAGAGG CTGCCCCCCT GCTCACTCAG CCAGGCCCTC ACCTACTCCC CGGACATCAC CACACCCCCA ACCCAGCTGC 10 TGCTCCAAAA GCTGGCCCAG GTGGCCACAG AAGAGCCTGA GAGACAGAGG CTGGAGGCCC TGTGCCAGCC CTCAGAGTAC AGCAAGTGGA AGTTCACCAA CAGCCCCACA TTCCTGGAGG TGCTAGAGGA GTTCCCGTCC CTGCGGGTGT CTGCTGGCTT CCTGCTCC CAGCTCCCCA TTCTGAAGCC CAGGTTCTAC TCCATCAGCT CCTCCCGGGA TCACACGCCC ACGGAGATCC ACCTGACTGT GGCCGTGGTC ACCTACCACA CCGGAGATGG CCAGGGTCCC CTGCACCACG GTGTCTGCAG CACATGGCTC AACAGCCTGA AGCCCCAAGA CCCAGTGCCC 15 TGCTTTGTGC GGAATGCCAG CGCCTTCCAC CTCCCCGAGG ATCCCTCCCA TCCTTGCATC CTCATCGGGC CTGGCACAGG CATCGTGCCC TTCCGCAGTT TCTGGCAGCA ACGGCTCCAT GACTCCCAGC ACAAGGGAGT GCGGGGAGGC CGCATGACCT TGGTGTTTGG GTGCCGCCGC CCAGATGAGG ACCACATCTA CCAGGAGGAG ATGCTGGAGA TGGCCCAGAA GGGGGTGCTG CATGCGGTGC ACACAGCCTA TTCCCGCCTG CCTGGCAAGC CCAAGGTCTA TGTTCAGGAC ATCCTGCGGC AGCAGCTGGC CAGCGAGGTG CTCCGTGTGC TCCACAAGGA 20 GCCAGGCCAC CTCTATGTTT GCGGGGATGT GCGCATGGCC CGGGACGTGG CCCACACCCT GAAGCAGCTG GTGGCTGCCA AGCTGAAATT GAATGAGGAG CAGGTCGAGG ACTATrTCTT TCAGCTCAAG AGCCAGAAGC GCTATCACGA AGATATCTTC GGTGCTGTAT TTCCTTACGA GGCGAAGAAG GACAGGGTGG CGGTGCAGCC CAGCAGCCTG GAGATGTCAG CGCTCTGAGG GCCTACAGGA GGGGTTAAAG CTGCCGGCAC AGAACTTAAG GATGGAGCCA GCTCTGCATT ATCTGAGGTC ACAGGGCCTG GGGAGATGGA GGAAAGTGAT ATCCCCCAGC 25 CTCAAGTCTT ATTTCCTCAA CGTTGCTCCC CATCAAGCCC TACTTGAC CTCCTAACAA GTAGCACCCT GGATTGATCG GAGCCTCCTC TCTCAAACTG GGGCCTCCCT GGTCCCTTGG AGACAAAATC TTAAATGCCA GGCCTGGCGA GTGGGTGAAA GATGGAACTT GCTGCTGAGT GCACCACTTC AAGTGACCAC CAGGAGGTGC TATCGCACCA CTGTGTATTT AACTGCCTTG TGTACAGTTA TTTATGCCTC TGTATTTAAA AAACTAACAC CCAGTCTGTT CCCCATGGCC ACT7GGGTCT TCCCTGTATG ATTCCTTGAT GGAGATATTT ACATGAATTG 30 CAT1TTACTT TAATC GAATTICCCAC TCTGCTGCCT GCTCCAGCAG ACGGACGCAC AGTAACATGG GCAACTTGAA GAGCGTGGCC CAGGAGCCTG GGCCACCCTG CGGCCTGGGG CTGGGGCTGG GCCTFGGGCT GTGCGGCAAG CAGGGCCCAG CCACCCCGGC CCCTGAGCCC AGCCGGGCCC CAGCATCCCT ACTCCCACCA GCGCCAGAAC ACAGCCCCCC GAGCTCCCCG CTAACCCAGC CCCCAGAGGG GCCCAAGTTC CCTCGTGTGA AGAACTGGGA GGTGGGGAGC ATCACCTATG ACACCCTCAG CGCCCAGGCG CAGCAGGATG GGCCCTGCAC 35 CCCAAGACGC TGCCTGGGCT CCCTGGTATT TCCACGGAAA CTACAGGGCC GGCCCTCCCC CGGCCCCCCG GCCCCTGAGC AGCTGCTGAG TCAGGCCCGG GACTCATCA ACCAGTACTA CAGCTCCATT AAGAGGAGCG GCTCCCAGGC CCACGAACAG CGGCTTCAAG AGGTGGAAGC CGAGGTGGCA GCCACAGGCA CCTACCAGCT TAGGGAGAGC GAGCTGGTGT TCGGGGCTAA GCAGGCCTGG CGCAACGCTC CCCGCTGCGT GGGCCGGATC CAGTGGGGGA AGCTGCAGGT GTTCGATGCC CGGGACTGCA GGTCTGCACA GGAAATGTTC ACCTACATCT 40 GCAACCACAT CAAGTATGCC ACCAACCGGG GCAACCTTCG CTCGGCCATC ACAGTGTTCC CGCAGCGCTG CCCTGGCCGA GGAGACTTCC GAATCTGGAA CAGCCAGCTG GTGCGCTACG CGGGCTACCG GCAGCAGGAC GGCTCTGTGC GGGGGGACCC AGCCAACGTG GAGATCACCG AGCTCTGCAT TCAGCACGGC TGGACCCCAG GAAACGGTCG CTTCGACGTG CTGCCCCTGC TGCTGCAGGC CCCAGATGAG CCCCCAGAAC TCTTCCTTCT GCCCCCCGAG CTGGTCCTTG AGGTGCCCCT GGAGCACCCC ACGCTGGAGT GGTTTGCAGC CCTGGGCCTG 45 CGCTGGTACG CCCTCCCGGC AGTGTCCAAC ATGCTGCTGG AAATTGGGGG CCTGGAGTTC CCCGCAGCCC CCTTCAGTGG CTGGTACATG AGCACTGAGA TCGGCACGAG GAACCTGTGT GACCCTCACC GCTACAACAT CCTGGAGGAT GTGGCTGTCT GCATGGACCT GGATACCCGG ACCACCTCGT CCCTGTGGAA AGACAAGGCA GCAGTGGAAA TCAACGTGGC CGTGCTGCAC AGTTACCAGC TAGCCAAAGT CACCATCGTG GACCACCACG CCGCCACGGC CTCTTTCATG AAGCACCTGG AGAATGAGCA GAAGGCCAGG GGGGGCTGCC CTGCAGACTG 50 GGCCTGGATC GTGCCCCCCA TCTCGGGCAG CCTCACTCCT GTTTCCATC AGGAGATGGT CAACTATTTC CTGTCCCCGG CCTTCCGCTA CCAGCCAGAC CCCTGGAAGG GGAGTGCCGC CAAGGGCACC GGCATCACCA GGAAGAAGAC CTTTAAAGAA GTGGCCAACG CCGTGAAGAT CTCCGCCTCG CTCATGGGCA CGGTGATGGC GAAGCGAGTG AAGGCGACAA TCCTGTATGG CTCCGAGACC GGCCGGGCCC AGAGCTACGC ACAGCAGCTG GGGAGACTCT TCCGGAAGGC T-TGATCCC CGGGTCCTGT GTATGGATGA GTATGACGTG GTGTCCCTCG 55 AACACGAGAC GCTGGTGCTG GTGGTAACCA GCACATTTGG GAATGGGGAT CCCCCGGAGA ATGGAGAGAG CTTTGCAGCT GCCCTGATGG AGATGTCCGG CCCCTACAAC AGCTCCCCTC GGCCGGAACA GCACAAGAGT TATAAGATCC GCTTCAACAG CATCTCCTGC TCAGACCCAC TGGTGTCCTC TTGGCGGCGG AAGAGGAAGG AGTCCAGTAA CACAGACAGT GCAGGGGCCC TGGGCACCCT CAGGTTCTGT GTGTTCGGGC TCGGCTCCCG GGCATACCCC CACTTCTGCG CCTGCTCG TGCCGTGGAC ACACGGCTGG AGGAACTGGG CGGGGAGCGG 60 CTGCTGCAGC TGGGCCAGGG CGACGAGCTG TGCGGCCAGG AGGAGGCCTT CCGAGGCTGG GCCCAGGCTG CCTTCCAGGC CGCCTGTGAG ACCTTCTGTG TGGGAGAGGA TGCCAAGGCC GCCGCCCGAG ACATCTTCAG CCCCAAACGG AGCTGGAAGC GCCAGAGGTA CCGGCTGAGC GCCCAGGCCG AGGGCCTGCA GTTGCTGCCA GGTCTGATCC ACGTGCACAG GCGGAAGATG TTCCAGGCTA CAATCCGCTC AGTGGAAAAC CTGCAAAGCA GCAAGTCCAC GAGGGCCACC ATCCTGGTGC GCCTGGACAC CGGAGGCCAG GAGGGGCTGC AGTACCAGCC 65 GGGGGACCAC ATAGGTGTCT GCCCGCCCAA CCGGCCCGGC CTTGTGGAGG CGCTGCTGAG CCGCGTGGAG GACCCGCCGG CGCCCACTGA GCCCGTGGCA GTAGAGCAGC TGGAGAAGGG CAGCCCTGGT GGCCCTCCCC WO 00/62736 PCT/USOO/08020 254 CCGGCTGGGT GCGGGACCCC CGGCTGCCCC CGTGCACGCT GCGCCAGGCT CTCACCTTCT TCCTGGACAT CACCTCCCCA CCCAGCCCTC AGCTCTTGCG GCTGCTCAGC ACCTTGGCAG AAGAGCCCAG GGAACAGCAG GAGCTGGAGG CCCTCAGCCA GGATCCCCGA CGCTACGAGG AGTGGAAGTG GTTCCGCTGC CCCACGCTGC TGGAGGTGCT GGAGCAGTTC CCGTCGGTGG CGCTGCCTGC CCCACTGCTC CTCACCCAGC TGCCTCTGCT 5 CCAGCCCCGG TACTACTCAG TCAGCTCGGC ACCCAGCACC CACCCAGGAG AGATCCACCT CACTGTAGCT GTGCTGGCAT ACAGGACTCA GGATGGGCTG GGCCCCCTGC ACTATGGAGT CTGCTCCACG TGGCTAAGCC AGCTCAAGCC CGGAGACCCT GTGCCCTGCT TCATCCGGGG GGCTCCCTCC TTCCGGCTGC CACCCGATCC CAGCTTGCCC TGCATCCTGG TGGGTCCAGG CACTGGCATT GCCCCCTTCC GGGGATrCTG GCAGGAGCGG CTGCATGACA TrGAGAGCAA AGGGCTGCAG CCCACTCCCA TGAC'TGGT GTTCGGCTGC CGATGCTCCC 10 AACTTGACCA TCTCTACCGC GACGAGGTGC AGAACGCCCA GCAGCGCGGG GTGTTTGGCC GAGTCCTCAC CGCCTTCTCC CGGGAACCTG ACAACCCCAA GACCTACGTG CAGGACATCC TGAGGACGGA GCTGGCTGCG GAGGTGCACC GCGTGCTGTG CCTCGAGCGG GGCCACATGT TTGTCTGCGG CGATGTTACC ATGGCAACCA ACGTCCTGCA GACCGTGCAG CGCATCCTGG CGACGGAGGG CGACATGGAG CTGGACGAGG CCGGCGACGT CATCGGCGTG CTGCGGGATC AGCAACGCTA CCACGAAGAC ATTTTCGGGC TCACGCTGCG CACCCAGGAG 15 GTGACAAGCC GCATACGCAC CCAGAGCT TCCTTGCAGG AGCGTCAGTT GCGGGGCGCA GTGCCCTGGG CGTTCGACCC TCCCGGCTCA GACACCAACA GCCCCTGAGA GCCGCCTGGC TTTCCCTTCC AGTTCCGGGA GAGCGGCTGC CCGACTCAGG TCCGCCCGAC CAGGATCAGC CCCGCTCCTC CCCTCTTGAG GTGGTGCCTT CTCACATCTG TCCAGAGGCT GCAAGGATTC AGCATTATTC CTCCAGGAAG GAGCAAAACG CCTCTTTTCC CTCTCTAGGC CTGTTGCCTC GGGCCTGGGT CCGCCTTAAT CTGGAAGGCC CCTCCCAGCA GCGGTACCCC 20 AGGGCCTACT GCCACCCGCT TCCTGTTCT TAGTCCGAAT GTTAGATTCC TCTTGCCTCT CTCAGGAGTA TC'TTACCTGT AAAGTCTAAT CTCTAAATCA AGTATATT ATTGAAGATT TACCATAAGG GACTGTGCCA GATGTTAGGA GAACTACTAA AGTGCCTACC CCAGCTC-3' (FRAG. NO:1897) (SEQ. ID NO: 3017) 5'-CATATGTATG GGAATACTGT ATCAGGCA TTATAAGGAA TGAAATTATA GGCCGGGCAT TGTGGCTAAC CCTTGTAATC CTAGCACTTT GAGAGGCTGA AGTGGGCAGA TCACTTGAGC TTCAGAGTTC GAGACCAGCA 25 TGGACAACAT GGTGAAACCC AGTCTCTACC AAAAACACAA AAATATTAGC TGGGTGTGGT GGTGCATGCC TGTAGTCCCA GCTACTCAGG AGGCTGAGGT GGGAGGATCG CTTGAGCCTG GGAGGCAGAA GTTGCAATGA GCAGAGATCG TGCCACTCCG CTCCAGTCTT GGTGACAGAA TGAGACTCCA TCTCAAAAAT AAATAAATAA ATAAATAAAA TAAATGAAAT GAAATTATAA GAAATTACCA CTTTTTCATG TAAGAAGTGA TCATTTCCAT TATAAGGGAA GGAATTTAAT CCTACCTGCC ATTCCACCAA AGCTTACCTA GTGCTAAAGG ATGAGGTGTT 30 AGTAAGACCA ACATCTCAGA GGCCTCTCTG TGCCAATAGC CTTCCTrCCT TTCCCTTCCA AAAACCTCAA GTGACTAGTT CAGAGGCCTG TCTGGAATAA TGGCATCATC TAATATCACT GGCCTTCTGG AACCTGGGCA TTTTCCAGTG TGTrCCATAC TGTCAATATT CCCCCAGCTT CCTGGACTCC TGTCACAAGC TGGAAAAGTG AGAGGATGGA CAGGGATTAA CCAGAGAGCT CCCTGCTGAG GAAAAAATCT CCCAGATGCT GAAAGTGAGG CCATGTGGCT TGGCCAAATA AAACCTGGCT CCGTGGTGCC TCTGTCTTAG CAGCCACCCT GCTGATGAAC 35 TGCCACCTTG GACTTGGGAC CAGAAAGAGG TGGGTrGGGT GAAGAGGCAC CACACAGAGT GATGTAACAG CAAGATCAGG TCACCCACAG GCCCTGGCAG TCACAGTCAT AAATTAGCTA ACTGTACACA AGCTGGGGAC ACTCCCTTTG GAAACCAAAA AAAAAAAAAA AAAAAAGAGA CCTTTATGCA AAAACAACTC TCTGGATGGC ATGGGGTGAG TATAAATACT TCTTGGCTGC CAGTGTGTTC ATAACTTTGT AGCGAGTCGA AAACTGAGGC TCCGGCCGCA GAGAACTCAG CCTCATTCCT GCTTTAAAAT CTCTCGGCCA CCTTTGATGA GGGGACTGGG 40 CAGTTCTAGA CAGTCCCGAA GTTCTCAAGG CACAGGTCTC TTCCTGGTT GACTGTCCTT ACCCCGGGGA GGCAGTGCAG CCAGCTGCAA GGTGAGTTGC C-3' (FRAG. NO:_)(SEQ. ID NO: 2506) 5'-CTGCTAAA ATCTCTCGGC CACCTTTGAT GAGGGGACTG GGCAGTTCTA GACAGTCCCG AAGITTCTCAA GGCACAGGTC TCTTCCTGGT TTGACTGTCC TTACCCCGGG GAGGCAGTGC AGCCAGCTGC AAGCCCCACA GTGAAGAACA TCTGAGCTCA AATCCAGATA AGTGACATAA GTGACCTGCT TTGTAAAGCC ATAGAGATGG 45 CCTGTCCTTG GAAATTTCTG TTCAAGACCA AATTCCACCA GTATGCAATG AATGGGGAAA AAGACATCAA CAACAATGTG GAGAAAGCCC CCTGTGCCAC CTCCAGTCCA GTGACACAGG ATGACCTTCA GTATCACAAC CTCAGCAAGC AGCAGAATGA GTCCCCGCAG CCCCTCGTGG AGACGGGAAA GAAGTCTCCA GAATCTCTGG TCAAGCTGGA TGCAACCCCA TTGTCCTCCC CACGGCATGT GAGGATCAAA AACTGGGGCA GCGGGATGAC TTTCCAAGAC ACACTTCACC ATAAGGCCAA AGGGATTTTA ACTTGCAGGT CCAAATCTTG CCTGGGGTCC 50 ATTATGACTC CCAAAAGTTT GACCAGAGGA CCCAGGGACA AGCCTACCCC TCCAGATGAG CTTCTACCTC AAGCTATCGA ATTTGTCAAC CAATATTACG GCTCCTTCAA AGAGGCAAAA ATAGAGGAAC ATCTGGCCAG GGTGGAAGCG GTAACAAAGG AGATAGAAAC AACAGGAACC TACCAACTGA CGGGAGATGA GCTCATCTTC GCCACCAAGC AGGCCTGGCG CAATGCCCCA CGCTGCATTG GGAGGATCCA GTGGTCCAAC CTGCAGGTCT TCGATGCCCG CAGCTGTTCC ACTGCCCGGG AAATGTTTGA ACACATCTGC AGACACGTGC GTTACTCCAC 55 CAACAATGGC AACATCAGGT CGGCCATCAC CGTGTTCCCC CAGCGGAGTG ATGGCAAGCA CGACTTCCGG GTGTGGAATG CTCAGCTCAT CCGCTATGCT GGCTACCAGA TGCCAGATGG CAGCATCAGA GGGGACCCTG CCAACGTGGA ATTCACTCAG CTGTGCATCG ACCTGGGCTG GAAGCCCAAG TACGGCCGCT TCGATGTGGT CCCCCTGGTC CTGCAGGCCA ATGGCCGTGA CCCTGAGCTC TTCGAAATCC CACCTGACCT TGTGCTTGAG GTGGCCATGG AACATCCCAA ATACGAGTGG TTTCGGGAAC TGGAGCTAAA GTGGTACGCC CTGCCTGCAG 60 TGGCCAACAT GCTGCTTGAG GTGGGCGGCC TGGAGTTCCC AGGGTGCCCC TTCAATGGCT GGTACATGGG CACAGAGATC GGAGTCCGGG ACTTCTGTGA CGTCCAGCGC TACAACATCC TGGAGGAAGT GGGCAGGAGA ATGGGCCTGG AAACGCACAA GCTGGCCTCG CTCTGGAAAG ACCAGGCTGT CGTTGAGATC AACATTGCTG TGATCCATAG TTTTCAGAAG CAGAATGTGA CCATCATGGA CCACCACTCG GCTGCAGAAT CCTTCATGAA GTACATGCAG AATGAATACC GGTCCCGTGG GGGCTGCCCG GCAGACTGGA TTTGGCTGGT CCCTCCCATG 65 TCTGGGAGCA TCACCCCCGT GTTTCACCAG GAGATGCTGA ACTACGTCCT GTCCCCTTTC TACTACTATC AGGTAGAGGC CTGGAAAACC CATGTCTGGC AGGACGAGAA GCGGAGACCC AAGAGAAGAG AGATTCCATT WO 00/62736 PCT/US00/08020 255 GAAAGTCTTG GTCAAAGCTG TGCTCTTGC CTGTATGCTG ATGCGCAAGA CAATGGCGTC CCGAGTCAGA GTCACCATCC TCTGCGAC AGAGACAGGA AAATCAGAGG CGCTGGCCTG GGACCTGGGG GCCTTATTCA GCTGTGCCTr CAACCCCAAG GTTGTCTGCA TGGATAAGTA CAGGCTGAGC TGCCTGGAGG AGGAACGGCT GCTGTTGGTG GTGACCAGTA CGTTTGGCAA TGGAGACTGC CCTGGCAATG GAGAGAAACT GAAGAAATCG 5 CTCTrCATGC TGAAAGAGCT CAACAACAAA TTCAGGTACG CTGTGTTGG CCTCGGCTCC AGCATGTACC CTCGGTTCTG CGCCTTTGCT CATGACATrG ATCAGAAGCT GTCCCACCTG GGGGCCTCTC AGCTCACCCC GATGGGAGAA GGGGATGAGC TCAGTGGGCA GGAGGACGCC TTCCGCAGCT GGGCCGTGCA AACCTTCAAG GCAGCCTGTG AGACGTTTGA TGTCCGAGGC AAACAGCACA TTCAGATCCC CAAGCTCTAC ACCTCCAATG TGACCTGGGA CCCGCACCAC TACAGGCTCG TGCAGGACTC ACAGCCTTTG GACCTCAGCA AAGCCCTCAG 10 CAGCATGCAT GCCAAGAACG TGTTCACCAT GAGGCTCAAA TCTCGGCAGA ATCTACAAAG TCCGACATCC AGCCGTGCCA CCATCCTGGT GGAACTCTCC TGTGAGGATG GCCAAGGCCT GAACTACCTG CCGGGGGAGC ACCTTGGGGT TTGCCCAGGC AACCAGCCGG CCCTGGTCCA AGGCATCCTG GAGCGAGTGG TGGATGGCCC CACACCCCAC CAGACAGTGC GCCTGGAGGA CCTGGATGAG AGTGGCAGCT ACTGGGTCAG TGACAAGAGG CTGCCCCCCT GCTCACTCAG CCAGGCCCTC ACCTACTCCC CGGACATCAC CACACCCCCA ACCCAGCTGC 15 TGCTCCAAAA GCTGGCCCAG GTGGCCACAG AAGAGCCTGA GAGACAGAGG CTGGAGGCCC TGTGCCAGCC CTCAGAGTAC AGCAAGTGGA AGTTCACCAA CAGCCCCACA TTCCTGGAGG TGCTAGAGGA GTTCCCGTCC CTGCGGGTGT CTGCTGGCTT CCTGCTTTCC CAGCTCCCCA TTCTGAAGCC CAGGTTCTAC TCCATCAGCT CCTCCCGGGA TCACACGCCC ACGGAGATCC ACCTGACTGT GGCCGTGGTC ACCTACCACA CCGGAGATGG CCAGGGTCCC CTGCACCACG GTGTCTGCAG CACATGGCTC AACAGCCTGA AGCCCCAAGA CCCAGTGCCC 20 TGCTTTGTGC GGAATGCCAG CGCCTTCCAC CTCCCCGAGG ATCCCTCCCA TCCTrGCATC CTCATCGGGC CTGGCACAGG CATCGTGCCC TTCCGCAGTT TCTGGCAGCA ACGGCTCCAT GACTCCCAGC ACAAGGGAGT GCGGGGAGGC CGCATGACCT TGGTGTTTGG GTGCCGCCGC CCAGATGAGG ACCACATCTA CCAGGAGGAG ATGCTGGAGA TGGCCCAGAA GGGGGTGCTG CATGCGGTGC ACACAGCCTA TTCCCGCCTG CCTGGCAAGC CCAAGGTCTA TGTTCAGGAC ATCCTGCGGC AGCAGCTGGC CAGCGAGGTG CTCCGTGTGC TCCACAAGGA 25 GCCAGGCCAC CTCTATGTTT GCGGGGATGT GCGCATGGCC CGGGACGTGG CCCACACCCT GAAGCAGCTG GTGGCTGCCA AGCTGAAATT GAATGAGGAG CAGGTCGAGG ACTATTTCTT TCAGCTCAAG AGCCAGAAGC GCTATCACGA AGATATCTTC GGTGCTGTAT TTCCTTACGA GGCGAAGAAG GACAGGGTGG CGGTGCAGCC CAGCAGCCTG GAGATGTCAG CGCTCTGAGG GCCTACAGGA GGGGTTAAAG CTGCCGGCAC AGAACTTAAG GATGGAGCCA GCTCTGCATT ATCTGAGGTC ACAGGGCCTG GGGAGATGGA GGAAAGTGAT ATCCCCCAGC 30 CTCAAGTCTT ATCCTCAA CGTTGCTCCC CATCAAGCCC TACTTGAC CTCCTAACAA GTAGCACCCT GGATTGATCG GAGCCTCCTC TCTCAAACTG GGGCCTCCCT GGTCCCTTGG AGACAAAATC TTAAATGCCA GGCCTGGCGA GTGGGTGAAA GATGGAACTT GCTGCTGAGT GCACCACTTC AAGTGACCAC CAGGAGGTGC TATCGCACCA CTGTGTATTT AACTGCCTTG TGTACAGTTA TTTATGCCTC TGTATTTAAA AAACTAACAC CCAGTCTGTT CCCCATGGCC ACTTGGGTCT TCCCTGTATG ATTCCTTGAT GGAGATATTT ACATGAAT7G 35 CATTTACTT TAATC-3' (FRAG. NO:_)(SEQ. ID NO:2507) 5'-GAATTCCCAC TCTGCTGCCT GCTCCAGCAG ACGGACGCAC AGTAACATGG GCAACTTGAA GAGCGTGGCC CAGGAGCCTG GGCCACCCTG CGGCCTGGGG CTGGGGCTGG GCCTTGGGCT GTGCGGCAAG CAGGGCCCAG CCACCCCGGC CCCTGAGCCC AGCCGGGCCC CAGCATCCCT ACTCCCACCA GCGCCAGAAC ACAGCCCCCC GAGCTCCCCG CTAACCCAGC CCCCAGAGGG GCCCAAGTTC CCTCGTGTGA AGAACTGGGA GGTGGGGAGC 40 ATCACCTATG ACACCCTCAG CGCCCAGGCG CAGCAGGATG GGCCCTGCAC CCCAAGACGC TGCCTGGGCT CCCTGGTATT TCCACGGAAA CTACAGGGCC GGCCCTCCCC CGGCCCCCCG GCCCCTGAGC AGCTGCTGAG TCAGGCCCGG GACTTCATCA ACCAGTACTA CAGCTCCATT AAGAGGAGCG GCTCCCAGGC CCACGAACAG CGGCTTCAAG AGGTGGAAGC CGAGGTGGCA GCCACAGGCA CCTACCAGCT TAGGGAGAGC GAGCTGGTGT TCGGGGCTAA GCAGGCCTGG CGCAACGCTC CCCGCTGCGT GGGCCGGATC CAGTGGGGGA AGCTGCAGGT 45 GTTCGATGCC CGGGACTGCA GGTCTGCACA GGAAATGTTC ACCTACATCT GCAACCACAT CAAGTATGCC ACCAACCGGG GCAACCTTCG CTCGGCCATC ACAGTGTTCC CGCAGCGCTG CCCTGGCCGA GGAGACTTCC GAATCTGGAA CAGCCAGCTG GTGCGCTACG CGGGCTACCG GCAGCAGGAC GGCTCTGTGC GGGGGGACCC AGCCAACGTG GAGATCACCG AGCTCTGCAT TCAGCACGGC TGGACCCCAG GAAACGGTCG CTTCGACGTG CTGCCCCTGC TGCTGCAGGC CCCAGATGAG CCCCCAGAAC TCTTCCTTCT GCCCCCCGAG CTGGTCCTTG 50 AGGTGCCCCT GGAGCACCCC ACGCTGGAGT GGTTTGCAGC CCTGGGCCTG CGCTGGTACG CCCTCCCGGC AGTGTCCAAC ATGCTGCTGG AAATTGGGGG CCTGGAGTTC CCCGCAGCCC CCTTCAGTGG CTGGTACATG AGCACTGAGA TCGGCACGAG GAACCTGTGT GACCCTCACC GCTACAACAT CCTGGAGGAT GTGGCTGTCT GCATGGACCT GGATACCCGG ACCACCTCGT CCCTGTGGAA AGACAAGGCA GCAGTGGAAA TCAACGTGGC CGTGCTGCAC AGTrACCAGC TAGCCAAAGT CACCATCGTG GACCACCACG CCGCCACGGC CTCTTTCATG 55 AAGCACCTGG AGAATGAGCA GAAGGCCAGG GGGGGCTGCC CTGCAGACTG GGCCTGGATC GTGCCCCCCA TCTCGGGCAG CCTCACTCCT GTCCATC AGGAGATGGT CAACTATTTC CTGTCCCCGG CCTTCCGCTA CCAGCCAGAC CCCTGGAAGG GGAGTGCCGC CAAGGGCACC GGCATCACCA GGAAGAAGAC CTTTAAAGAA GTGGCCAACG CCGTGAAGAT CTCCGCCTCG CTCATGGGCA CGGTGATGGC GAAGCGAGTG AAGGCGACAA TCCTGTATGG CTCCGAGACC GGCCGGGCCC AGAGCTACGC ACAGCAGCTG GGGAGACTCT TCCGGAAGGC 60 TTTTGATCCC CGGGTCCTGT GTATGGATGA GTATGACGTG GTGTCCCTCG AACACGAGAC GCTGGTGCTG GTGGTAACCA GCACATTTGG GAATGGGGAT CCCCCGGAGA ATGGAGAGAG CITTGCAGCT GCCCTGATGG AGATGTCCGG CCCCTACAAC AGCTCCCCTC GGCCGGAACA GCACAAGAGT TATAAGATCC GCTTCAACAG CATCTCCTGC TCAGACCCAC TGGTGTCCTC TTGGCGGCGG AAGAGGAAGG AGTCCAGTAA CACAGACAGT GCAGGGGCCC TGGGCACCCT CAGGTTCTGT GTGTTCGGGC TCGGCTCCCG GGCATACCCC CACTTCTGCG 65 CCTTTGCTCG TGCCGTGGAC ACACGGCTGG AGGAACTGGG CGGGGAGCGG CTGCTGCAGC TGGGCCAGGG CGACGAGCTG TGCGGCCAGG AGGAGGCCTT CCGAGGCTGG GCCCAGGCTG CCTTCCAGGC CGCCTGTGAG WO 00/62736 PCT/US00/08020 256 ACCTTCTGTG TGGGAGAGGA TGCCAAGGCC GCCGCCCGAG ACATCTrCAG CCCCAAACGG AGCTGGAAGC GCCAGAGGTA CCGGCTGAGC GCCCAGGCCG AGGGCCTGCA GTTGCTGCCA GGTCTGATCC ACGTGCACAG GCGGAAGATG TTCCAGGCTA CAATCCGCTC AGTGGAAAAC CTGCAAAGCA GCAAGTCCAC GAGGGCCACC ATCCTGGTGC GCCTGGACAC CGGAGGCCAG GAGGGGCTGC AGTACCAGCC GGGGGACCAC ATAGGTGTCT 5 GCCCGCCCAA CCGGCCCGGC CTTGTGGAGG CGCTGCTGAG CCGCGTGGAG GACCCGCCGG CGCCCACTGA GCCCGTGGCA GTAGAGCAGC TGGAGAAGGG CAGCCCTGGT GGCCCTCCCC CCGGCTGGGT GCGGGACCCC CGGCTGCCCC CGTGCACGCT GCGCCAGGCT CTCACCTTCT TCCTGGACAT CACCTCCCCA CCCAGCCCTC AGCTCTTGCG GCTGCTCAGC ACCTrGGCAG AAGAGCCCAG GGAACAGCAG GAGCTGGAGG CCCTCAGCCA GGATCCCCGA CGCTACGAGG AGTGGAAGTG GTTCCGCTGC CCCACGCTGC TGGAGGTGCT GGAGCAGTrC 10 CCGTCGGTGG CGCTGCCTGC CCCACTGCTC CTCACCCAGC TGCCTCTGCT CCAGCCCCGG TACTACTCAG TCAGCTCGGC ACCCAGCACC CACCCAGGAG AGATCCACCT CACTGTAGCT GTGCTGGCAT ACAGGACTCA GGATGGGCTG GGCCCCCTGC ACTATGGAGT CTGCTCCACG TGGCTAAGCC AGCTCAAGCC CGGAGACCCT GTGCCCTGCT TCATCCGGGG GGCTCCCTCC TTCCGGCTGC CACCCGATCC CAGCITTGCCC TGCATCCTGG TGGGTCCAGG CACTGGCATT GCCCCCTTCC GGGGATTCTG GCAGGAGCGG CTGCATGACA TTGAGAGCAA 15 AGGGCTGCAG CCCACTCCCA TGACTTTGGT GTTCGGCTGC CGATGCTCCC AACTTGACCA TCTCTACCGC GACGAGGTGC AGAACGCCCA GCAGCGCGGG GTGTTTGGCC GAGTCCTCAC CGCCTTCTCC CGGGAACCTG ACAACCCCAA GACCTACGTG CAGGACATCC TGAGGACGGA GCTGGCTGCG GAGGTGCACC GCGTGCTGTG CCTCGAGCGG GGCCACATGT TTGTCTGCGG CGATGTTACC ATGGCAACCA ACGTCCTGCA GACCGTGCAG CGCATCCTGG CGACGGAGGG CGACATGGAG CTGGACGAGG CCGGCGACGT CATCGGCGTG CTGCGGGATC 20 AGCAACGCTA CCACGAAGAC ATITCGGGC TCACGCTGCG CACCCAGGAG GTGACAAGCC GCATACGCAC CCAGAGCTTT TCCTTGCAGG AGCGTCAGTT GCGGGGCGCA GTGCCCTGGG CGTTCGACCC TCCCGGCTCA GACACCAACA GCCCCTGAGA GCCGCCTGGC TTTCCCTrCC AGTTCCGGGA GAGCGGCTGC CCGACTCAGG TCCGCCCGAC CAGGATCAGC CCCGCTCCTC CCCTCTTGAG GTGGTGCCTT CTCACATCTG TCCAGAGGCT GCAAGGATTC AGCATTATTC CTCCAGGAAG GAGCAAAACG CCTCTITCC CTCTCTAGGC CTGTTGCCTC 25 GGGCCTGGGT CCGCCTTAAT CTGGAAGGCC CCTCCCAGCA GCGGTACCCC AGGGCCTACT GCCACCCGCT TCCTGTTTCT TAGTCCGAAT GTTAGATTCC TCTTGCCTCT CTCAGGAGTA TCTTACCTGT AAAGTCTAAT CTCTAAATCA AGTATTTATT ATTGAAGATT TACCATAAGG GACTGTGCCA GATGTTAGGA GAACTACTAA AGTGCCTACC CCAGCTC-3' (FRAG. NO: ) (SEQ. ID NO:2508) 5'-CCCCGGGG-3' (FRAG. NO:1898) (SEQ. ID NO: 1911) 30 5'-GGGGCCGCTGGG-3' (FRAG. NO:1899) (SEQ. ID NO:1912) 5'-GGGGGTGTGG-3' (FRAG. NO:1900) (SEQ. ID NO: 1913) 5'-CTGCCTCCCCGGGGT-3' (FRAG. NO:1442)(SEQ. ID NO:1451) 5'-TTCTGCTGCTTGCTG-3' (FRAG. NO:1443)(SEQ. ID NO:1452) 5'-CTTCTTTCCCGTCTCC-3' (FRAG. NO:1444)(SEQ. ID NO:1453) 35 5'-CTTCTTTCCCGTCTCC-3' (FRAG. NO:1445)(SEQ. ID NO:1454) 5'-TTTTGCCTCTTTG-3' (FRAG. NO:1446)(SEQ. ID NO:1455) 5'-GGTTCCTGTTGTTTCT-3' (FRAG. NO:1447)(SEQ. ID NO:1456) 5'-GGCCTGCTTGGTGGCG-3' (FRAG. NO:1448)(SEQ. ID NO:1457) 5'-GCTTGTGCGTCC-3' (FRAG. NO:1449)(SEQ. ID NO:1458) 40 5'-TCTCTCTTCTCTTGGGTCTCCGCTTCTCGTCCTGCC-3' (FRAG. NO:1450)(SEQ. ID NO:1459) 5'-TTTTCCTGTCTCTGTCGC-3' (FRAG. NO:1451)(SEQ. ID NO:1460) 5'-GCCGTTCCTCCTCC-3' (FRAG. NO:1452)(SEQ. ID NO:1461) 5'-GGCGTCCTCCTGCCC-3' (FRAG. NO:1453)(SEQ. ID NO:1462) 5'-TGTGCTGTT7GCCTCGG-3' (FRAG. NO:1454)(SEQ. ID NO: 1463) 45 5'-GTGGTGCGGGTCCC-3' (FRAG. NO: 1455)(SEQ. ID NO: 1464) 5'-GGTGCTCCCCCGGC-3' (FRAG. NO: 1456)(SEQ. ID NO: 1465) 5'-GGGCCGGCTGGTTGCCTGGGC-3' (FRAG. NO:1457)(SEQ. ID NO: 1466) 5'-CTGTCTGGTGGGGTGTGGGGCC-3' (FRAG. NO: 1458)(SEQ. ID NO: 1467) 5'-GCTGGGTTGGGGGTGTGGTG-3' (FRAG. NO: 1459)(SEQ. ID NO: 1468) 50 5'-GGCTCTTCTGTGGCC-3' (FRAG. NO: 1460)(SEQ. ID NO:1469) 5'-TGTGGGGCTGTTGGTG-3' (FRAG. NO:1461)(SEQ. ID NO: 1470) 5'-TCTCTGTGGGCGTGTG-3' (FRAG. NO: 1462)(SEQ. ID NO: 1471) 5'-CTGGGTCTTGGGGCT'TC-3' (FRAG. NO: 1463)(SEQ. ID NO: 1472) 5'-CTCCCTTIGTGCTGGG-3' (FRAG. NO: 1464)(SEQ. ID NO: 1473) 55 5'-TGCGGCCTCCCCGC-3' (FRAG. NO:1465)(SEQ. ID NO:1474) 5'-CCCCCT'TCTGGGCC-3' (FRAG. NO: 1466)(SEQ. ID NO: 1475) 5'-GGTGGCCTGGCTCCTTFGTGG-3' (FRAG. NO: 1467)(SEQ. ID NO: 1476) 5'-GCGCTTCTGGCTCTTG-3' (FRAG. NO: 1468)(SEQ. ID NO: 1477) 5'-CCCTGTCCTrCTTCGCCTCGT-3' (FRAG. NO: 1469)(SEQ. ID NO: 1478) 60 5'-GGCTGCTGGGCTGC-3' (FRAG. NO:1470)(SEQ. ID NO:1479) 5'-CTGCCCCBGTTTTTGBTCCTCBCBTGCCGTGGGGBGGBCBBTGG-3'(FRAG. NO:1901) (SEQ. ID NO: 1914) NF-kB Nucleic Acids and Antisense Oligonucleotide Fragments 5'-CGGCCCTTCT CACTGGAGGC ACCGGGCAGT CCTCCATGGG AGGGTTGGGC TTGGCCGGGG CTGCCCGGTG CCTCCTCTTG GCTGGTCCCT CGTTGTCCTT GGGCCCCGC TCCCGCTGCT CGGCCTCCGT GTTCTTTGGC 65 CTCTTGCTCC GCCTGCTGTC TTGTCCCGTC CCCTCCTCGC TrGCGTCC CTCTTCCTTG TCTTCCAGGC CTTCCTCCGC TTCCGCTGCT GGGGCCCGCG CCGGGGGGGC GCTCGGCTCC GCGGCTTCCT CCCCGGCTGG WO 00/62736 PCT/USOO/08020 257 GGGGTCCTGG TCTCCGGGGC CTGCGGCTCG CGGGCTCGGG GCTGCGTGCG CCGCGCGCGG CGTCCGCGGT GGGTGGCGCT GTCCCGCCGT GGTGTGTCTC CGTTCTCGTC CTGCGCCGTC CTGGTCTGCC CGTGGGGTCC TGGGCGTGGT GGGGGGCGTC TGGTGCCTCG TCTGCCCCGT GGGGCTTCGG GCTCGGGGCT GTTCGTCCCC CCTGCCGCTC TGTGGCCTCC GGGGCTCCTC GTTTTCGCTG CTTCGGGTGT CCTTCTCGGC GTGTGGCCCC 5 GGGTCCCGGC CCTGCTGGGC TGGGCGGGGT CGCTGCCCTG GGCTTCTGGC CCGTCTGGTT GTCTGTCGGT GCTTGTCTCG GGTTTCTGGC CTCTGTGCTG GGCGCTTCTC TGCCTCCTGC TCCGCCCTCC TGGTGGCTCG GCTGGGGGTG CCCGTGCGGG GGTGGGTGTG GGGTGTTTTC GGGGTCCTCC CCTTCCC-3' (FRAG. NO:1902) (SEQ. ID NO:1915) 5'-GGGCGGGGTCGC-3' (FRAG. NO:1903) (SEQ. ID NO:1916) 10 5'-GCGCCGTCC-3' (FRAG. NO:1904) (SEQ. ID NO:1917) 5'-GGGCGTGGTGG-3' (FRAG. NO:1905) (SEQ. ID NO:1918) 5'-GTTGGGCTTGGCCGGGG-3' (FRAG. NO: 1471)(SEQ. ID NO: 1480) 5'-CTGCCCGGTGCCTCC-3' (FRAG. NO: 1472)(SEQ. ID NO: 1481) 5'-TCTTGGCTGGTCCCTCGT-3' (FRAG. NO: 1473)(SEQ. ID NO: 1482) 15 5'-TGTCCTrGGGCCCC-3' (FRAG. NO:1474)(SEQ. ID NO:1483) 5'-GCTCCCGCTGCTCGGCCTCCGT-3' (FRAG. NO: 1475)(SEQ. ID NO: 1484) 5'-GTTCTTTGGCCTCTTGCTCC-3' (FRAG. NO: 1476)(SEQ. ID NO: 1485) 5'-GCCTGCTGTCTTGTCC-3' (FRAG. NO: 1477)(SEQ. ID NO: 1486) 5'-CGTCCCCTCCTCGCTTGCGTTTC-3' (FRAG. NO: 1478)(SEQ. ID NO: 1487) 20 5'-CCTCTTCCTTGTCTrCCA-3' (FRAG. NO:1479)(SEQ. ID NO: 1488) 5'-GGCCTTCCTCCGCTTCCGCTGC-3' (FRAG. NO: 1480)(SEQ. ID NO: 1489) 5'-TGGGGCCCGCGCCGG-3' (FRAG. NO: 1481)(SEQ. ID NO: 1490) 5'-GGGGGCGCTCGGCTCCGCGGCTTCCTCCCCGG-3' (FRAG. NO:1482)(SEQ. ID NO:1491) 5'-CTGGGGGGTCCTGG-3' (FRAG. NO: 1483)(SEQ. ID NO:1492) 25 5'-TCTCCGGGGCCTGCGGCTCGC-3' (FRAG. NO: 1484)(SEQ. ID NO: 1493) 5'-GGGCTCGGGGCTGCGTGCGCC-3' (FRAG. NO:1485)(SEQ. ID NO:1494) 5'-GCGCGCGGCGTCCGCGGTG-3' (FRAG. NO: 1486)(SEQ. ID NO: 1495) 5'-GGTGGCGCTGTCCCGCC-3' (FRAG. NO: 1487)(SEQ. ID NO: 1496) 5'-GTGGTGTGTCTCCGTTCTCGTCCTGCGCCGTC-3' (FRAG. NO:1488)(SEQ. ID NO:1497) 30 5'-CTGGTCTGCCCGTGG-3' (FRAG. NO: 1489)(SEQ. ID NO: 1498) 5'-GGTCCTGGGCGTGGTGG-3' (FRAG. NO: 1490)(SEQ. ID NO: 1499) 5'-GGGGCGTCTGGTGC-3' (FRAG. NO:1491)(SEQ. ID NO:1500) 5'-CTCGTCTGCCCCGTG-3' (FRAG. NO: 1492)(SEQ. ID NO: 1501) 5'-GGGCTTrCGGGCTCGG-3' (FRAG. NO: 1493)(SEQ. ID NO: 1502) 35 5'-GGCTGTTCGTCCCCCCTGCCGCTCTGTGGCCTCC-3' (FRAG. NO: 1494)(SEQ. ID NO: 1503) 5'-GGGGCTCCTCGTTTTC-3' (FRAG. NO: 1495)(SEQ. ID NO: 1504) 5'-GCTGCTTCGGGTGTCCTTCTC-3' (FRAG. NO: 1496)(SEQ. ID NO: 1505) 5'-GGCGTGTGGCCCCGG-3' (FRAG. NO: 1497)(SEQ. ID NO: 1506) 5'-GTCCCGGCCCTGCTGGGCTGGGCGGGGTC-3' (FRAG. NO: 1498)(SEQ. ID NO: 1507) 40 5'-GCTGCCCTGGGCTTCTGGCCCGTCT-3' (FRAG. NO: 1499)(SEQ. ID NO: 1508) 5'-GGFGTCTGTCGGT-3' (FRAG. NO: 1500)(SEQ. ID NO: 1509) 5'-GCTTGTCTCGGGTTTCTGG-3' (FRAG. NO:1501)(SEQ. ID NO:1510) 5'-CCTCTGTGCTGGGC-3' (FRAG. NO: 1502)(SEQ. ID NO: 1511) 5'-GCTTCTCTGCCTCCTGCTCC-3' (FRAG. NO: 1503)(SEQ. ID NO: 1512) 45 5'-GCCCTCCTGGTGGCTC-3' (FRAG. NO:1504)(SEQ. ID NO: 1513) 5'-GGCTGGGGGTGCCCGTGCG-3' (FRAG. NO: 1505)(SEQ. ID NO: 1514) 5'-GGGGTGGGTGTGGGGTGTT-3' (FRAG. NO: 1506)(SEQ. ID NO: 1515) 5'-TTCGGGGTCCTCCCCTTCCC-3' (FRAG. NO: 1507)(SEQ. ID NO: 1516) 5'-CGGCCCTTCTCACTGGAGGCACCGGGCAGTCCTCCATGGGAGG-3' (FRAG.NO:1906)(SEQ.ID NO:1919) 50 Human Major Basic Protein Nucleic Acids and Antisense Oligonucleotide Fragments 5'-GTT TCA TCT TGG CTT TAT CCTCT CCC CTT GTr CCT CCC CTCT CCT GCT CTG GRG TCT CCT C TTC CCT CCC TCC CCT GCC GTG TTG TCT GTG GGT GTC GTT TCG CTC TTG TTG CCC TGG GCC CTT CCC TGC TGG GGG GGA GTT TCA TCT TGG GTT TCB TCT TGG CTT TBT CCTCT CCC CTT GTT CCT CCC CTCT CCT GCT CTG GRG TCT CCT C TTC CCT CCC TCC CCT GCC GTG TTG TCT GTG GGT GTC GTT TCG CTC TTG TTG CCC 55 TGG GCC CTT CCC TGC TGG GGG GGB GTT TCB TCT TGG-3' (FRAG. ID:1907) (SEQ. ID NO:1920) 5'-GGG GGA GTT-3' (FRAG. ID:1908) (SEQ. ID NO:1921) 5'-G CCC TGG GCC C-3' (FRAG. ID:1909) (SEQ. ID NO:1922) 5'-GTT TCA TCT TGG CTT TAT CC-3' (FRAG. NO:1508) (SEQ. ID NO:1517) 5'-TCT CCC CTT GTT CCT CCC C-3' (FRAG. NO:1509)(SEQ. ID NO:1518) 60 5'-TCT CCT GCT CTG GRG TCT CCT C-3' (FRAG. NO:1510)(SEQ. ID NO:1519) 5'-TTC CCT CCC TCC CCT GCC-3' (FRAG. NO: 1511)(SEQ. ID NO: 1520) 5'-GTG TTG TCT GTG GGT GTC C-3' (FRAG. NO:1512)(SEQ. ID NO: 1521) 5'-GTT TCG CTC TTG TTG CCC-3' (FRAG. NO: 1513)(SEQ. ID NO:1522) 5'-TGG GCC CTT CCC TGC TGG-3' (FRAG. NO: 1514)(SEQ. ID NO: 1523) 65 5'-GGG GGA GTT TCA TCT TGG-3' (FRAG. NO:1515)(SEQ. ID NO: 1524) WO 00/62736 PCT/USOO/08020 258 5'-GTT TCA TCT TGG CTT TAT CCTCT CCC CTT GTT CCT CCC CTCT CCT GCT CTG GRG TCT CCT C TTC CCT CCC TCC CCT GCC GTG TTG TCT GTG GGT GTC GTT TCG CTC TTG TTG CCC TGG GCC CTT CCC TGC TGG GGG GGA GTT TCA TCT TGG-3' (FRAG. ID:1910) (SEQ. ID NO:1923) 5'-GTT TCB TCT TGG CTT TBT CCTCT CCC CTT GTT CCT CCC CTCT CCT GCT CTG GRG TCT CCT C TTC CCT 5 CCC TCC CCT GCC GTG TTG TCT GTG GGT GTC GTT TCG CTC TTG TTG CCC TGG GCC CTT CCC TGC TGG GGG GGB GTT TCB TCT TGG-3' (FRAG. ID:1911) (SEQ. ID NO:1924) Human Eosinophil Major Basic Protein Nucleic Acids and Antisense Oligonucleotide Fragments 5'-GGG GGB GTT TCB TCT TGG CTT T-3' (FRAG. NO:1516)(SEQ. ID NO:1525) 5'-GGG GGB GTT TCB TCT TGG CTT-3' (FRAG. NO: 1517)(SEQ. ID NO: 1526) 10 5'-GGG GGB GTT TCB TCT TGG CT-3' (FRAG. NO: 1518)(SEQ. ID NO:1527) 5'-GGG GGB GTT TCB TCT TGG C-3' (FRAG. NO:1519)(SEQ. ID NO: 1528) 5'-GGG GGB GTT TCB TCT TGG-3' (FRAG. NO:1520)(SEQ. ID NO: 1529) 5'-GGG GGB GTT TCB TCT TG-3' (FRAG. NO: 1521)(SEQ. ID NO: 1530) 5'-GGG GGB GTT TCB TCT T-3' (FRAG. NO:1522)(SEQ. ID NO: 1531) 15 5'-GGG GGB GTT TCB TCT-3' (FRAG. NO: 1523)(SEQ. ID NO: 1532) 5'-GGG GGB GTT TCB TC-3' (FRAG. NO:1524)(SEQ. ID NO: 1533) 5'-GGG GGB GTT TCB T-3' (FRAG. NO:1525)(SEQ. ID NO: 1534) 5'-GGG GGB GTT TCB-3' (FRAG. NO:1526)(SEQ. ID NO: 1535) 5'-GG GGB GTT TCB TCT TGG CTT T-3' (FRAG. NO:1527)(SEQ. ID NO: 1536) 20 5'-GG GGB GTT TCB TCT TGG CTT-3' (FRAG. NO:1528)(SEQ. ID NO: 1537) 5'-GG GGB GTT TCB TCT TGG CT-3' (FRAG. NO:1529)(SEQ. ID NO: 1538) 5'-GG GGB GTT TCB TCT TGG C-3' (FRAG. NO:1530)(SEQ. ID NO: 1539) 5'-GG GGB GTT TCB TCT TGG-3' (FRAG. NO:1531)(SEQ. ID NO: 1540) 5'-GG GGB GTT TCB TCT TG-3' (FRAG. NO:1532)(SEQ. ID NO: 1541) 25 5'-GG GGB GTT TCB TCT T-3' (FRAG. NO:1533)(SEQ. ID NO: 1542) 5'-GG GGB GTT TCB TCT-3' (FRAG. NO:1534)(SEQ. ID NO: 1543) 5'-GG GGB GTT TCB TC-3' (FRAG. NO: 1535)(SEQ. ID NO: 1544) 5'-GG GGB GTT TCB T-3' (FRAG. NO:1536)(SEQ. ID NO: 1545) 5'-G GGB GTT TCB TCT TGG CTT T-3' (FRAG. NO:1537)(SEQ. ID NO: 1546) 30 5'-G GGB GTT TCB TCT TGG CTT-3' (FRAG. NO: 1538)(SEQ. ID NO: 1547) 5'-G GGB GTT TCB TCT TGG CT-3' (FRAG. NO: 1539)(SEQ. ID NO: 1548) 5'-G GGB GTT TCB TCT TGG C-3' (FRAG. NO:1540)(SEQ. ID NO: 1549) 5'-G GGB GTT TCB TCT TGG-3' (FRAG. NO:1541)(SEQ. ID NO: 1550) 5'-G GGB GTT TCB TCT TG-3' (FRAG. NO:1542)(SEQ. ID NO: 1551) 35 5'-G GGB GTT TCB TCT T-3' (FRAG. NO:1543)(SEQ. ID NO: 1552) 5'-G GGB GTT TCB TCT-3' (FRAG. NO:1544)(SEQ. ID NO: 1553) 5'-G GGB GTT TCB TC-3' (FRAG. NO:1545)(SEQ. ID NO: 1554) 5'-GGB GTT TCB TCT TGG CTT T-3' (FRAG. NO:1546)(SEQ. ID NO: 1555) 5'-GGB GTT TCB TCT TGG CTT-3' (FRAG. NO:1547)(SEQ. ID NO: 1556) 40 5'-GGB GTT TCB TCT TGG CT-3' (FRAG. NO: 1548)(SEQ. ID NO: 1557) 5'-GGB GTT TCB TCT TGG C-3' (FRAG. NO: 1549)(SEQ. ID NO: 1558) 5'-GGB GTT TCB TCT TGG-3' (FRAG. NO:1550)(SEQ. ID NO: 1559) 5'-GGB GTT TCB TCT TG-3' (FRAG. NO: 1551)(SEQ. ID NO: 1560) 5'-GGB GTT TCB TCT T-3' (FRAG. NO: 1552)(SEQ. ID NO: 1561) 45 5'-GGB GTT TCB TCT-3' (FRAG. NO:1553)(SEQ. ID NO: 1562) 5'-GB GTT TCB TCT TGG CTT T-3' (FRAG. NO:1554)(SEQ. ID NO: 1563) 5'-GB GTT TCB TCT TGG CTT-3' (FRAG. NO: 1555)(SEQ. ID NO: 1564) 5'-GB GTT TCB TCT TGG CT-3' (FRAG. NO:1556)(SEQ. ID NO: 1565) 5'-GB GTT TCB TCT TGG C-3' (FRAG. NO:1557)(SEQ. ID NO: 1566) 50 5'-GB GTT TCB TCT TGG-3' (FRAG. NO:1558)(SEQ. ID NO: 1567) 5'-GB GTT TCB TCT TG-3' (FRAG. NO:1559)(SEQ. ID NO: 1568) 5'-GB GTT TCB TCT T-3' (FRAG. NO: 1560)(SEQ. ID NO: 1569) 5'-B GTT TCB TCT TGG CTT T-3' (FRAG. NO: 1561)(SEQ. ID NO: 1570) 5'-B GTT TCB TCT TGG CTT-3' (FRAG. NO:1562)(SEQ. ID NO: 1571) 55 5'-B GT TCB TCT TGG CTT-3' (FRAG. NO:1563)(SEQ. ID NO: 1572) 5'-B GTT TCB TCT TGG CT-3' (FRAG. NO:1564)(SEQ. ID NO: 1573) 5'-B GTT TCB TCT TGG C-3' (FRAG. NO: 1565)(SEQ. ID NO: 1574) 5'-B GTT TCB TCT TGG-3' (FRAG. NO:1565)(SEQ. ID NO: 1575) 5'-B GTT TCB TCT TG-3' (FRAG. NO: 1567)(SEQ. ID NO: 1576) 60 5'-GTT TCB TCT TGG CTT T-3' (FRAG. NO:1568)(SEQ. ID NO: 1577) 5'-GTT TCB TCT TGG CTT-3' (FRAG. NO: 1569)(SEQ. ID NO: 1578) 5'-GTT TCB TCT TGG CT-3' (FRAG. NO:1570)(SEQ. ID NO: 1579) 5'-GTT TCB TCT TGG C-3' (FRAG. NO:1571)(SEQ. ID NO: 1580) 5'-GTT TCB TCT TGG-3' (FRAG. NO:1572)(SEQ. ID NO: 1581) 65 5'-TT TCB TCT TGG CTT T-3' (FRAG. NO: 1573)(SEQ. ID NO: 1582) WO 00/62736 PCT/USOO/08020 259 5'-TT TCB TCT TGG CTT-3' (FRAG. NO: 1574)(SEQ. ID NO: 1583) 5'-TT TCB TCT TGG CT-3 (FRAG. NO:1575)(SEQ. ID NO: 1584) 5'-TT TCB TCT TGG C-3' (FRAG. NO:1576)(SEQ. ID NO: 1585) 5'-T TCB TCT TGG CTT T-3' (FRAG. NO:1577)(SEQ. ID NO: 1586) 5 5'-T TCB TCT TGG CT-3' (FRAG. NO: 1578)(SEQ. ID NO: 1587) 5'-T TCB TCT TGG CT-3' (FRAG. NO: 1579)(SEQ. ID NO: 1588) 5'-TCB TCT TGG CTT T-3 (FRAG. NO:1580)(SEQ. ID NO: 1589) 5'-TCB TCT TGG CTT-3' (FRAG. NO:1581)(SEQ. ID NO: 1590) 5'-GGG GGB GTT TCB TCT TGG CTT T-3' (FRAG. NO: 1582)(SEQ. ID NO:1591) 10 5'-GG GGB GTT TCB TCT TGG CTT T-3' (FRAG. NO:1583)(SEQ. ID NO: 1592) 5'-G GGB GTT TCB TCT TGG CTT T-3' (FRAG. NO:1584)(SEQ. ID NO: 1593) 5'-GGB GTT TCB TCT TGG CTT T-3' (FRAG. NO:1585)(SEQ. ID NO: 1594) 5'-GB GTT TCB TCT TGG CTT T-3' (FRAG. NO:1586)(SEQ. ID NO: 1595) 5'-B GTT TCB TCT TGG CTT T-3' (FRAG. NO:1587)(SEQ. ID NO: 1596) 15 5'-GTT TCB TCT TGG CTT T-3' (FRAG. NO: 1588)(SEQ. ID NO: 1597) 5'-TT TCB TCT TGG CTT T-3' (FRAG. NO: 1589)(SEQ. ID NO: 1598) 5'-T TCB TCT TGG CTT T-3' (FRAG. NO:1590)(SEQ. ID NO: 1599) 5'-TCB TCT TGG CTT T-3' (FRAG. NO:1591)(SEQ. ID NO: 1600) 5'-CB TCT TGG CTT T-3' (FRAG. NO:1592)(SEQ. ID NO: 1601) 20 5'-GGG GGB GTT TCB TCT TGG CTT-3' (FRAG. NO: 1593)(SEQ. ID NO: 1602) 5'-GG GGB GTT TCB TCT TGG CTT-3' (FRAG. NO: 1594)(SEQ. ID NO: 1603) 5'-G GGB GTT TCB TCT TGG CTT-3' (FRAG. NO:1595)(SEQ. ID NO: 1604) 5'-GGB GTT TCB TCT TGG CTT-3' (FRAG. NO: 1596)(SEQ. ID NO: 1605) 5'-GB GTT TCB TCT TGG CTT-3' (FRAG. NO: 1597)(SEQ. ID NO: 1606) 25 5'-B GTT TCB TCT TGG CTT-3' (FRAG. NO:1598)(SEQ. ID NO: 1607) 5'-GTT TCB TCT TGG CTT-3' (FRAG. NO: 1599)(SEQ. ID NO: 1608) 5'-T TCB TCT TGG CTT-3' (FRAG. NO:1600)(SEQ. ID NO: 1609) 5'-T TCB TCT TGG CTT-3' (FRAG. NO: 1601)(SEQ. ID NO: 1610) 5'-TCB TCT TGG CTT-3' (FRAG. NO:1602)(SEQ. ID NO: 1611) 30 5'-GGG GGB GTT TCB TCT TGG CT-3' (FRAG. NO:1603)(SEQ. ID NO: 1612) 5'-GG GGB GTU TCB TCT TGG CT-3' (FRAG. NO:1604)(SEQ. ID NO: 1613) 5'-G GGB GTT TCB TCT TGG CT-3' (FRAG. NO:1605)(SEQ. ID NO: 1614) 5'-GGB GTT TCB TCT TGG CT-3' FRAGG. NO:1606)(SEQ. ID NO: 1615) 5'-GB GT TCB TCT TGG CT-3' (FRAG. NO:1607)(SEQ. ID NO: 1616) 35 5'-B GTT TCB TCT TGG CT-3' FRAGG. NO:1608)(SEQ. ID NO: 1617) 5'-GTT TCB TCT TGG CT-3' (FRAG. NO: 1609)(SEQ. ID NO: 1618) 5'-TT TCB TCT TGG CT-3' (FRAG. NO:1610)(SEQ. ID NO: 1619) 5'-T TCB TCT TGG CT-3' FRAGG. NO:1611)(SEQ. ID NO: 1620) 5'-GGG GGB GTT TCB TCT TGG C-3' (FRAG. NO: 1612)(SEQ. ID NO: 1621) 40 5'-GG GGB GTT TCB TCT TGG C-3' (FRAG. NO: 1613)(SEQ. ID NO: 1622) 5'-G GGB GTT TCB TCT TGG C-3' (FRAG. NO:1614)(SEQ. ID NO: 1623) 5'-GGB GTT TCB TCT TGG C-3' FRAGG. NO: 1615)(SEQ. ID NO: 1624) 5'-GB GTT TCB TCT TGG C-3' (FRAG. NO: 1616)(SEQ. ID NO: 1625) 5'-B GTT TCB TCT TGG C-3' (FRAG. NO:1617)(SEQ. ID NO: 1626) 45 5'-GTT TCB TCT TGG C-3' (FRAG. NO: 1618)(SEQ. ID NO: 1627) 5'-TT TCB TCT TGG C-3' (FRAG. NO:1619)(SEQ. ID NO: 1628) 5'-GGG GGB GTT TCB TCT TGG-3' (FRAG. NO: 1620)(SEQ. ID NO: 1629) 5'-GG GGB GTT TCB TCT TGG-3' (FRAG. NO: 1621)(SEQ. ID NO: 1630) 5'-G GGB GTT TCB TCT TGG-3' (FRAG. NO: 1622)(SEQ. ID NO: 1631) 50 5'-GGB GTT TCB TCT TGG-3' (FRAG. NO: 1623)(SEQ. ID NO: 1632) 5'-GB GTT TCB TCT TGG-3' (FRAG. NO: 1624)(SEQ. ID NO: 1633) 5'-B GTT TCB TCT TGG-3' (FRAG. NO: 1625)(SEQ. ID NO: 1634) 5'-GTT TCB TCT TGG-3' (FRAG. NO:1626)(SEQ. ID NO: 1635) 5'-GGG GGB GTT TCB TCT TG-3' (FRAG. NO: 1627)(SEQ. ID NO: 1636) 55 5'-GG GGB GTT TCB TCT TG-3' (FRAG. NO: 1628)(SEQ. ID NO: 1637) 5'-G GGB GTT TCB TCT TG-3' (FRAG. NO: 1629)(SEQ. ID NO: 1638) 5'-GGB GTT TCB TCT TG-3' (FRAG. NO:1630)(SEQ. ID NO: 1639) 5'-GB GTT TCB TCT TG-3' (FRAG. NO:1631)(SEQ. ID NO: 1640) 5'-B GTT TCB TCT TG-3' (FRAG. NO:1632)(SEQ. ID NO: 1641) 60 5'-GGG GGB GTT TCB TCT T-3' (FRAG. NO: 1633)(SEQ. ID NO: 1642) 5'-GG GGB GTT TCB TCT T-3' (FRAG. NO:1634)(SEQ. ID NO: 1643) 5'-G GGB GTT TCB TCT T-3' (FRAG. NO: 1635)(SEQ. ID NO: 1644) 5'-G GGB GTT TCB TCT T-3' (FRAG. NO: 1636)(SEQ. ID NO: 1645) 5'-GGB GTT TCB TCT T-3' (FRAG. NO:1637)(SEQ. ID NO: 1646) 65 5'-GB GTT TCB TCT T-3' (FRAG. NO: 1638)(SEQ. ID NO: 1647) 5'-GGG GGB GTU TCB TCT-3' (FRAG. NO:1639)(SEQ. ID NO: 1648) WO 00/62736 PCT/USOO/08020 260 5'-GG GGB GTT TCB TCT-3' (FRAG. NO:1640)(SEQ. ID NO: 1649) 5'-G GGB GTT TCB TCT-3' (FRAG. NO: 1641)(SEQ. ID NO: 1650) 5'-GGB GTT TCB TCT-3' (FRAG. NO: 1642)(SEQ. ID NO: 1651) 5'-GGG GGB GTT TCB TC-3' (FRAG. NO: 1643)(SEQ. ID NO: 1652) 5 5'-GG GGB GTT TCB TC-3' (FRAG. NO:1644)(SEQ. ID NO: 1653) 5'-G GGB GTT TCB TC-3' (FRAG. NO:1645)(SEQ. ID NO: 1654) 5'-GGG GGB GTT TCB T-3' (FRAG. NO:1646)(SEQ. ID NO: 1655) 5'-GG GGB GTT TCB T-3' (FRAG. NO:1647)(SEQ. ID NO: 1656) 5'-GGG GGB GTT TCB-3' (FRAG. NO:1648)(SEQ. ID NO: 1657) 10 5'-TCT CCC CT GTT CCT CCC C-3' (FRAG. NO: 1649)(SEQ. ID NO: 1658) 5'-TCT CCT GCT CTG GTG TCT CCT C-3' (FRAG. NO:1650)(SEQ. ID NO: 1659) 5'-TTC CCT CCC TCC CCT GCC-3' (FRAG. NO:1651)(SEQ. ID NO: 1660) 5'-GTG TTG TCT GTG GGT GTC C-3' (FRAG. NO: 1652)(SEQ. ID NO: 1661) 5'-GTT TCG CTC TTG TTG CCC-3' -3' (FRAG. NO: 1653)(SEQ. ID NO: 1661) 15 5'-TGG GCC CTT CCC TGC TGG-3' (FRAG. NO: 1654)(SEQ. ID NO: 1663) 5'-GGG GGB G-3' (FRAG. NO:1912)(SEQ. ID NO:1925) 5'-GTG GGT GTC C-3' (FRAG. NO:1913) (SEQ. ID NO: 1926) BP-1 Nucleic Acids and Antisense Oligonucleotide Fragments 5'-CCGTGTTGTC BGTGGTGCTG CCCGTTTGBG GTBTGGCGCT CCBCCBBTTC CCTTTTCTCC TTGTTTTCCG 20 TTTCTCTTGC CGTCTGTGGT T-3' (FRAG. NO:1914) (SEQ. ID NO: 1927) 5'-CCCGTTTGBGGTBTGGC-3'(FRAG. NO:1915) (SEQ. ID NO: 1928) 5'-GCTCCBCCBBTTCCCTTTTCTCC-3'(FRAG. NO:1916) (SEQ. ID NO: 1929) 5'-TTGTTTTCCGTTTCTCTTG-3'(FRAG. NO:1917) (SEQ. ID NO: 1930) 5'-CCGTCTGTGGTT-3'(FRAG. NO:1918) (SEQ. ID NO: 1931) 25 5'-CCCGTTTGAGGTATGGC-3'(FRAG. NO:1919) (SEQ. ID NO: 1932) 5'-GCTCCBCCAATTCCCTTTTCTCC-3'(FRAG. NO:1920) (SEQ. ID NO: 1933) C/EBPNucleic Acids and Antisense Oligonucleotide Antisense Oligonucleotide Fragments 5'-GGGCCCBGCCCCGCCGCCTTTTCTBGCCCC GGCC-3' (FRAG. NO:1921) (SEQ. ID NO: 1934) 5'-GGGCCCBGCCCCGCCGCCTTCTBGCCCC GGC-3' (FRAG. NO:1922) (SEQ. ID NO: 1935) 30 5'-GGGCCCB GCCCCGCCGCCTTTTCTBGCCCCGG-3' (FRAG. NO:1923) (SEQ. ID NO: 1936) 5'-GGGCCCBGCCCCGCCGCCT'TTCTBGCCCCG-3' (FRAG. NO:1924) (SEQ. ID NO: 1937) 5'-GGGCCCBGCCCCGCCGCCTTTTCTBGCCCC-3' (FRAG. NO:1925) (SEQ. ID NO: 1938) 5'-GGGCCCBGCCCCGCCGCCTTTTCTBGCCC-3' (FRAG. NO:1926) (SEQ. ID NO: 1939) 5'-GGGCCCBGCCCCGCCGCCTTTTCTBGCC-3' (FRAG. NO:1927) (SEQ. ID NO: 1940) 35 5'-GGGCCCBGCCCCGCCGCCTTTTCTBGC-3' (FRAG. NO:1928) (SEQ. ID NO: 1941) 5'-GGGCCCBGCCCCGCCGCCTTTTCTBG-3' (FRAG. NO:1929) (SEQ. ID NO: 1942) 5'-GGGCCCBGCCCCGCCGCCTTTTCTB-3' (FRAG. NO:1930) (SEQ. ID NO: 1943) 5'-GGGCCCBGCCCCGCCGCCTTTTCT-3' (FRAG. NO:1931) (SEQ. ID NO:1942) 1944) 5'-GGGCCCBGCCCCGCCGCCTTTTC-3' (FRAG. NO:1932) (SEQ. ID NO: 1945) 40 5'-GGGCCCBGCCCCGCCGCCTTTT-3'(FRAG. NO:1933) (SEQ. ID NO: 1946) 5'-GGGCCCBGCCCCGCCGCCTTT-3' (FRAG. NO:1934) (SEQ. ID NO: 1947) [1945)] 5'-GGGCCCBGCCCCGCCGCCTT-3' (FRAG. NO:1935) (SEQ. ID NO: 1948) 5'-GGGCCCBGCCCCGCCGCCT-3' (FRAG. NO:1936) (SEQ. ID NO: 1949) 5'-GGGCCCBGCCCCGCCGCC-3' (FRAG. NO:1937) (SEQ. ID NO: 1950) 45 5'-GGGCCCBGCCCCGCCGC-3' (FRAG. NO:1938) (SEQ. ID NO: 1951) 5'-GGGCCCBGCCCCGCCG-3' (FRAG. NO:1939) (SEQ. ID NO: 1952) 5'-GGGCCCBGCCCCGCC-3' (FRAG. NO:1940) (SEQ. ID NO: 1953) 5'-GGGCCCBGCCCCGC-3' (FRAG. NO:1941) (SEQ. ID NO: 1954) 5'-GGGCCCBGCCCCG-3' (FRAG. NO:1942) (SEQ. ID NO: 1955) 50 5'-GGGCCCBGCCCC-3' (FRAG. NO:1943) (SEQ. ID NO: 1956) 5'-GGGCCCBGCCC-3' (FRAG. NO:1944) (SEQ. ID NO: 1957) 5'-GGCCCBGCCCCGCCGCCTTTTCTBGCCCCGGC-3' (FRAG. NO:1945) (SEQ. ID NO: 1958) 5'-GCCCBGCCCCGCCGCCTTTTCTBGCCCCGGC-3' (FRAG. NO:1946) (SEQ. ID NO: 1959) 5'-CCCBGCCCCGCCGCCTTTTCTBGCCCCGGC-3' (FRAG. NO:1947) (SEQ. ID NO: 1960) 55 5'-CCBGCCCCGCCGCCTTTTCTBGCCCCGGC-3' (FRAG. NO:1948) (SEQ. ID NO: 1961) 5'-CBGCCCCGCCGCCTTTTCTBGCCCCGGC-3' (FRAG. NO:1948) (SEQ. ID NO: 1962) 5'-BGCCCCGCCGCCTTTTCTBGCCCCGGC-3' (FRAG. NO:1950) (SEQ. ID NO: 1963) 5'-GCCCCGCCGCCTTTTCTBGCCCCGGC-3' (FRAG. NO:1951) (SEQ. ID NO: 1964) 5'-CCCCGCCGCCTTTTCTBGCCCCGGC-3' (FRAG. NO:1952) (SEQ. ID NO: 1965) 60 5'-CCCGCCGCCTTTTCTBGCCCCGGC-3' (FRAG. NO:1953) (SEQ. ID NO: 1966) 5'-CCGCCGCCTTTTCTBGCCCCGGC-3' (FRAG. NO:1954) (SEQ. ID NO: 1967) 5'-CGCCGCCTTTTCTBGCCCCGGC-3' (FRAG. NO:1955) (SEQ. ID NO: 1968) WO 00/62736 PCT/US00/08020 261 5'-GCCGCCTTTTCTBGCCCCGGC-3' (FRAG. NO:1956) (SEQ. ID NO: 1969) 5'-CCGCCTTTTCTBGCCCCGGC-3' FRAGG. NO:1957) (SEQ. ID NO: 1970) 5'-CGCCTTTTCTBGCCCCGGC-3' (FRAG. NO:1958) (SEQ. ID NO: 1971) 5'-GCCTTTTCTBGCCCCGGC-3' (FRAG. NO:1959) (SEQ. ID NO: 1972) 5 5'-CCTTTTCTBGCCCCGGC-3' (FRAG. NO:1960) (SEQ. ID NO: 1973) 5'-CTTTTCTBGCCCCGGC-3' FRAGG. NO:1961) (SEQ. ID NO: 1974) 5'-TTTTCTBGCCCCGGC-3' FRAGG. NO:1962) (SEQ. ID NO: 1975) 5'-TTTCTBGCCCCGGC-3' FRAGG. NO:1963) (SEQ. ID NO: 1976) 5'-TTCTBGCCCCGGC-3' (FRAG. NO:1964) (SEQ. ID NO: 1977) 10 5'-TCTBGCCCCGGC-3' (FRAG. NO:1965) (SEQ. ID NO: 1978) 5'-CTBGCCCCGGC-3' (FRAG. NO:1966) (SEQ. ID NO: 1979) 5'-GCGBGGCTGTCBCCTCGCTGGGCCC-3'(FRAG. NO:1967) (SEQ. ID NO: 1980) 5'-GCGBGGCTGTCBCCTCGCTGGGCC-3' FRAGG. NO:1968) (SEQ. ID NO: 1981) 5'-GCGBGGCTGTCBCCTCGCTGGGC-3' (FRAG. NO:1969) (SEQ. ID NO: 1982) 15 5'-GCGBGGCTGTCBCCTCGCTGGG-3' FRAGG. NO:1970) (SEQ. ID NO:1983) 5'-GCGBGGCTGTCBCCTCGCTGG-3' FRAGG. NO:1971) (SEQ. ID NO:1984) 5'-GCGBGGCTGTCBCCTCGCTG-3'(FRAG. NO:1972) (SEQ. ID NO:1985) 5'-GCGBGGCTGTCBCCTCGCT-3' FRAGG. NO:1973) (SEQ. ID NO:1986) 5'-GCGBGGCTGTCBCCTCGC-3 (FRAG. NO:1974) (SEQ. ID NO:1987) 20 5'-GCGBGGCTGTCBCCTCG-3' (FRAG. NO:1975) (SEQ. ID NO:1988) 5'-GCGBGGCTGTCBCCTC-3' FRAGG. NO:1976) (SEQ. ID NO:1989) 5'-GCGBGGCTGTCBCCT-3' FRAGG. NO:1977) (SEQ. ID NO:1990) 5'-GCGBGGCTGTCBCC-3' (FRAG. NO:1978) (SEQ. ID NO:1991) 5'-GCGBGGCTGTCBC-3' (FRAG. NO:1979) (SEQ. ID NO:1992) 25 5'-GCGBGGCTGTCB-3' FRAGG. NO:1980) (SEQ. ID NO:1993) 5'-GCGBGGCTGTC-3' FRAGG. NO:1981) (SEQ. ID NO:1994) 5'-GCGBGGCTGT-3' (FRAG. NO:1982) (SEQ. ID NO:1995) 5'-CGBGGCTGTCBCCTCGCTGGGCCC-3' FRAGG. NO:1983) (SEQ. ID NO:1996) 5'-GBGGCTGTCBCCTCGCTGGGCCC-3 FRAGG. NO:1984) (SEQ. ID NO:1997) 30 5'-BGGCTGTCBCCTCGCTGGGCCC-3'(FRAG. NO:1985) (SEQ. ID NO:1998) 5'-GGCTGTCBCCTCGCTGGGCCC-3' FRAGG. NO:1986) (SEQ. ID NO:1999) 5'-GCTGTCBCCTCGCTGGGCCC-3' FRAGG. NO:1987) (SEQ. ID NO:2000) 5'-CTGTCBCCTCGCTGGGCCC-3'(FRAG. NO:1988) (SEQ. ID NO:2001) 5'-TGTCBCCTCGCTGGGCCC-3' FRAGG. NO:1989) (SEQ. ID NO:2002) 35 5'-GTCBCCTCGCTGGGCCC-3' FRAGG. NO:1990) (SEQ. ID NO:2003) 5'-TCBCCTCGCTGGGCCC-3'(FRAG. NO:1991) (SEQ. ID NO:2004) 5'-CBCCTCGCTGGGCCC-3' FRAGG. NO:1992) (SEQ. ID NO:2005) 5'-BCCTCGCTGGGCCC-3' FRAGG. NO:1993) (SEQ. ID NO:2006) 5'-CCTCGCTGGGCCC-3' FRAGG. NO:1994) (SEQ. ID NO:2007) 40 5'-CTCGCTGGGCCC-3' FRAGG. NO:1995) (SEQ. ID NO:2008) 5'-TCGCTGGGCCC-3' FRAGG. NO:1996) (SEQ. ID NO:2009) 5'-CGCTGGGCCC-3' FRAGG. NO:1997) (SEQ. ID NO:2010) 5'-GCGCGGCCGTCBTGGCGGCGTCGGGCCGGGC-3'(FRAG. NO:1998) (SEQ. ID NO:2011) 5'-GCGCGGCCGTCBTGGCGGCGTCGGGCCGGG-3'(FRAG. NO:1999) (SEQ. ID NO:2012) 45 5'-GCGCGGCCGTCBTGGCGGCGTCGGGCCGG-3'(FRAG. NO:2000) (SEQ. ID NO:2013) 5'-GCGCGGCCGTCBTGGCGGCGTCGGGCCG-3' FRAGG. NO:2001) (SEQ. ID NO:2014) 5'-GCGCGGCCGTCBTGGCGGCGTCGGGCC-3' FRAGG. NO:2002) (SEQ. ID NO:2015) 5'-GCGCGGCCGTCBTGGCGGCGTCGGGC-3' FRAGG. NO:2003) (SEQ. ID NO:2016) 5'-GCGCGGCCGTCBTGGCGGCGTCGGG-3' FRAGG. NO:2004) (SEQ. ID NO:2017) 50 5'-GCGCGGCCGTCBTGGCGGCGTCGG-3' (FRAG. NO:2005) (SEQ. ID NO:2018) 5'-GCGCGGCCGTCBTGGCGGCGTCG-3'(FRAG. NO:2006) (SEQ. ID NO:2019) 5'-GCGCGGCCGTCBTGGCGGCGTC-3' FRAGG. NO:2007) (SEQ. ID NO:2020) 5'-GCGCGGCCGTCBTGGCGGCGT-3' FRAGG. NO:2008) (SEQ. ID NO:2021) 5'-GCGCGGCCGTCBTGGCGGCG-3' FRAGG. NO:2009) (SEQ. ID NO:2022) 55 5'-GCGCGGCCGTCBTGGCGGC-3' FRAGG. NO:2010) (SEQ. ID NO:2023) 5'-GCGCGGCCGTCBTGGCGG-3' FRAGG. NO:2011) (SEQ. ID NO:2024) 5'-GCGCGGCCGTCBTGGCG-3 FRAGG. NO:2012) (SEQ. ID NO:2025) 5'-GCGCGGCCGTCBTGGC-3' FRAGG. NO:2013) (SEQ. ID NO:2026) 5'-GCGCGGCCGTCBTGG-3' FRAGG. NO:2014) (SEQ. ID NO:2027) 60 5'-GCGCGGCCGTCBTG-3' FRAGG. NO:2015) (SEQ. ID NO:2028) 5'-GCGCGGCCGTCBT-3' FRAGG. NO:2016) (SEQ. ID NO:2029) 5'-GCGCGGCCGTCB-3' FRAGG. NO:2017) (SEQ. ID NO:2030) WO 00/62736 PCT/US00/08020 262 5'-GCGCGGCCGTC-3' (FRAG. NO:2018) (SEQ. ID NO:2031) 5'-GCGCGGCCGT-3' (FRAG. NO:2019) (SEQ. ID NO:2032) 5'-CGCGGCCGTCBTGGCGGCGTCGGGCCGGGC-3' (FRAG. NO:2020) (SEQ. ID NO:2033) 5'-GCGGCCGTCBTGGCGGCGTCGGGCCGGGC-3'(FRAG. NO:2021) (SEQ. ID NO:2034) 5 5'-CGGCCGTCBTGGCGGCGTCGGGCCGGGC-3' (FRAG. NO:2022) (SEQ. ID NO:2035) 5'-GGCCGTCBTGGCGGCGTCGGGCCGGGC-3' (FRAG. NO:2023) (SEQ. ID NO:2036) 5'-GCCGTCBTGGCGGCGTCGGGCCGGGC-3' (FRAG. NO:2024) (SEQ. ID NO:2037) 5'-CCGTCBTGGCGGCGTCGGGCCGGGC-3' (FRAG. NO:2025) (SEQ. ID NO:2038) 5'-CGTCBTGGCGGCGTCGGGCCGGGC-3' (FRAG. NO:2026) (SEQ. ID NO:2039) 10 5'-GTCBTGGCGGCGTCGGGCCGGGC-3' (FRAG. NO:2027) (SEQ. ID NO:2040) 5'-TCBTGGCGGCGTCGGGCCGGGC-3' (FRAG. NO:2028) (SEQ. ID NO:2041) 5'-CBTGGCGGCGTCGGGCCGGGC-3' (FRAG. NO:2029) (SEQ. ID NO:2042) 5'-BTGGCGGCGTCGGGCCGGGC-3'(FRAG. NO:2030) (SEQ. ID NO:2043) 5'-TGGCGGCGTCGGGCCGGGC-3' FRAGG. NO:2031) (SEQ. ID NO:2044) 15 5'-GGCGGCGTCGGGCCGGGC-3' (FRAG. NO:2032) (SEQ. ID NO:2045) 5'-GCGGCGTCGGGCCGGGC-3'(FRAG. NO:2033) (SEQ. ID NO:2046) 5'-CGGCGTCGGGCCGGGC-3' (FRAG. NO:2034) (SEQ. ID NO:2047) 5'-GGCGTCGGGCCGGGC-3' (FRAG. NO:2035) (SEQ. ID NO:2048) 5'-GCGTCGGGCCGGGC-3' (FRAG. NO:2036) (SEQ. ID NO:2049) 20 5'-CGTCGGGCCGGGC-3' (FRAG. NO:2037) (SEQ. ID NO:2050) 5'-GTCGGGCCGGGC-3' (FRAG. NO:2038) (SEQ. ID NO:2051) 5'-TCGGGCCGGGC-3' (FRAG. NO:2039) (SEQ. ID NO:2052) 5'-CGGGCCGGGC-3' (FRAG. NO:2040) (SEQ. ID NO:2053) 5'-CCGCBGGCCBGGGCGCGCCGCCGGCCGGGCCG-3' (FRAG. NO:2041) (SEQ. ID NO:2054) 25 5'-CCGCBGGCCBGGGCGCGCCGCCGGCCGGGCC-3' (FRAG. NO:2042) (SEQ. ID NO:2055) 5'-CCGCBGGCCBGGGCGCGCCGCCGGCCGGGC-3'(FRAG. NO:2043) (SEQ. ID NO:2056) 5'-CCGCBGGCCBGGGCGCGCCGCCGGCCGGG-3' (FRAG. NO:2044) (SEQ. ID NO:2057) 5'-CCGCBGGCCBGGGCGCGCCGCCGGCCGG-3'(FRAG. NO:2045) (SEQ. ID NO:2058) 5'-CCGCBGGCCBGGGCGCGCCGCCGGCCG-3' (FRAG. NO:2046) (SEQ. ID NO:2059) 30 5'-CCGCBGGCCBGGGCGCGCCGCCGGCC-3' (FRAG. NO:2047) (SEQ. ID NO:2060) 5'-CCGCBGGCCBGGGCGCGCCGCCGGC-3' (FRAG. NO:2048) (SEQ. ID NO:2061) 5'-CCGCBGGCCBGGGCGCGCCGCCGG-3' (FRAG. NO:2049) (SEQ. ID NO:2062) 5'-CCGCBGGCCBGGGCGCGCCGCCG-3' (FRAG. NO:2050) (SEQ. ID NO:2063) 5'-CCGCBGGCCBGGGCGCGCCGCC-3' (FRAG. NO:2051) (SEQ. ID NO:2064) 35 5'-CCGCBGGCCBGGGCGCGCCGC-3' (FRAG. NO:2052) (SEQ. ID NO:2065) 5'-CCGCBGGCCBGGGCGCGCCG-3' (FRAG. NO:2053) (SEQ. ID NO:2066) 5'-CCGCBGGCCBGGGCGCGCC-3' (FRAG. NO:2054) (SEQ. ID NO:2067) 5'-CCGCBGGCCBGGGCGCGC-3' (FRAG. NO:2055) (SEQ. ID NO:2068) 5'-CCGCBGGCCBGGGCGCG-3' (FRAG. NO:2056) (SEQ. ID NO:2069) 40 5'-CCGCBGGCCBGGGCGC-3' (FRAG. NO:2057) (SEQ. ID NO:2070) 5'-CCGCBGGCCBGGGCG-3' (FRAG. NO:2058) (SEQ. ID NO:2071) 5'-CCGCBGGCCBGGGC-3' (FRAG. NO:2059) (SEQ. ID NO:2072) 5'-CCGCBGGCCBGGG-3' (FRAG. NO:2060) (SEQ. ID NO:2073) 5'-CCGCBGGCCBGG-3' (FRAG. NO:2061) (SEQ. ID NO:2074) 45 5'-CCGCBGGCCBG-3' (FRAG. NO:2062) (SEQ. ID NO:2075) 5'-CCGCBGGCCB-3' (FRAG. NO:2063) (SEQ. ID NO:2076) 5'-CCGCBGGCC-3' (FRAG. NO:2064) (SEQ. ID NO:2077) 5'-CGCBGGCCBGGGCGCGCCGCCGGCCGGGCCG-3' (FRAG. NO:2065) (SEQ. ID NO:2078) 5'-GCBGGCCBGGGCGCGCCGCCGGCCGGGCCG-3' (FRAG. NO:2066) (SEQ. ID NO:2079) 50 5'-CBGGCCBGGGCGCGCCGCCGGCCGGGCCG-3' (FRAG. NO:2067) (SEQ. ID NO:2080) .5'-BGGCCBGGGCGCGCCGCCGGCCGGGCCG-3' (FRAG. NO:2068) (SEQ. ID NO:2081) 5'-GGCCBGGGCGCGCCGCCGGCCGGGCCG-3' (FRAG. NO:2069) (SEQ. ID NO:2082) 5'-GCCBGGGCGCGCCGCCGGCCGGGCCG-3' (FRAG. NO:2070) (SEQ. ID NO:2083) 5'-CCBGGGCGCGCCGCCGGCCGGGCCG-3'(FRAG. NO:2071) (SEQ. ID NO:2084) 55 5'-CBGGGCGCGCCGCCGGCCGGGCCG-3' (FRAG. NO:2072) (SEQ. ID NO:2085) 5'-BGGGCGCGCCGCCGGCCGGGCCG-3' (FRAG. NO:2073) (SEQ. ID NO:2086) 5'-GGGCGCGCCGCCGGCCGGGCCG-3' (FRAG. NO:2074) (SEQ. ID NO:2087) 5'-GGCGCGCCGCCGGCCGGGCCG-3' (FRAG. NO:2075) (SEQ. ID NO:2088) 5'-GCGCGCCGCCGGCCGGGCCG-3' (FRAG. NO:2076) (SEQ. ID NO:2089) 60 5'-CGCGCCGCCGGCCGGGCCG-3' (FRAG. NO:2077) (SEQ. ID NO:2090) 5'-GCGCCGCCGGCCGGGCCG-3' (FRAG. NO:2078) (SEQ. ID NO:2091) 5'-CGCCGCCGGCCGGGCCG-3'(FRAG. NO:2079) (SEQ. ID NO:2092) WO 00/62736 PCT/US00/08020 263 5'-GCCGCCGGCCGGGCCG-3' (FRAG. NO:2080) (SEQ. ID NO:2093) 5'-CCGCCGGCCGGGCCG-3' (FRAG. NO:2081) (SEQ. ID NO:2094) 5'-CGCCGGCCGGGCCG-3' (FRAG. NO:2082) (SEQ. ID NO:2095) 5'-GCCGGCCGGGCCG-3' FRAGG. NO:2083) (SEQ. ID NO:2096) 5 5'-CCGGCCGGGCCG-3' (FRAG. NO:2084) (SEQ. ID NO:2097) 5'-CGGCCGGGCCG-3' (FRAG. NO:2085) (SEQ. ID NO:2098) 5'-GGCCGGGCCG-3' (FRAG. NO:2086) (SEQ. ID NO:2099) 5'-GGGCGCBGGCTCCGCB-3' (FRAG. NO:2087) (SEQ. ID NO:2100) 5'-GGGCCCCTGGCTCGGCCCCGCGGCCCGGCTTGCCCGCCCGGCCCGG-3'(FRAG.NO:2088)(SEQ.ID NO:2101) 10 5'-GGGCCCCTGGCTCGGCCCCGCGGCCCGGCTTGCCCGCCCGGCCCG-3' (FRAG.NO:2089)(SEQ.ID NO:2102) 5'-GGGCCCCTGGCTCGGCCCCGCGGCCCGGCTTGCCCGCCCGGCCC-3' (FRAG.NO:2090)(SEQ.ID NO:2103) 5'-GGGCCCCTGGCTCGGCCCCGCGGCCCGGCTTGCCCGCCCGGCC-3' (FRAG. NO:2091) (SEQ. ID NO:2104) 5'-GGGCCCCTGGCTCGGCCCCGCGGCCCGGCTTGCCCGCCCGGC-3' (FRAG. NO:2092) (SEQ. ID NO:2105) 5'-GGGCCCCTGGCTCGGCCCCGCGGCCCGGCTTGCCCGCCCGG-3' (FRAG. NO:2093) (SEQ. ID NO:2106) 15 5'-GGGCCCCTGGCTCGGCCCCGCGGCCCGGCTTGCCCGCCCG-3' FRAGG. NO:2094) (SEQ. ID NO:2107) 5'-GGGCCCCTGGCTCGGCCCCGCGGCCCGGCTTGCCCGCCC-3' (FRAG. NO:2095) (SEQ. ID NO:2108) 5'-GGGCCCCTGGCTCGGCCCCGCGGCCCGGCTTGCCCGCC-3'(FRAG. NO:2096) (SEQ. ID NO:2109) 5'-GGGCCCCTGGCTCGGCCCCGCGGCCCGGCTTGCCCGC-3' (FRAG. NO:2097) (SEQ. ID NO:2110) 5'-GGGCCCCTGGCTCGGCCCCGCGGCCCGGCTTGCCCG-3' (FRAG. NO:2098) (SEQ. ID NO:2111) 20 5'-GGGCCCCTGGCTCGGCCCCGCGGCCCGGCTTGCCC-3' (FRAG. NO:2099) (SEQ. ID NO:2112) 5'-GGGCCCCTGGCTCGGCCCCGCGGCCCGGCTTGCC-3' (FRAG. NO:2100) (SEQ. ID NO:2113) 5'-GGGCCCCTGGCTCGGCCCCGCGGCCCGGCTTGC-3' (FRAG. NO:2101) (SEQ. ID NO:2114) 5'-GGGCCCCTGGCTCGGCCCCGCGGCCCGGCTTG-3' (FRAG. NO:2102) (SEQ. ID NO:2115) 5'-GGGCCCCTGGCTCGGCCCCGCGGCCCGGCTT-3'(FRAG. NO:2103) (SEQ. ID NO:2116) 25 5'-GGGCCCCTGGCTCGGCCCCGCGGCCCGGCT-3' (FRAG. NO:2104) (SEQ. ID NO:2117) 5'-GGGCCCCTGGCTCGGCCCCGCGGCCCGGC-3' (FRAG. NO:2105) (SEQ. ID NO:2118) 5'-GGGCCCCTGGCTCGGCCCCGCGGCCCGG-3' (FRAG. NO:2106) (SEQ. ID NO:2119) 5'-GGGCCCCTGGCTCGGCCCCGCGGCCCG-3' (FRAG. NO:2107) (SEQ. ID NO:2120) 5'-GGGCCCCTGGCTCGGCCCCGCGGCCC-3' (FRAG. NO:2108) (SEQ. ID NO:2121) 30 5'-GGGCCCCTGGCTCGGCCCCGCGGCC-3' (FRAG. NO:2109) (SEQ. ID NO:2122) 5'-GGGCCCCTGGCTCGGCCCCGCGGC-3' (FRAG. NO:2110) (SEQ. ID NO:2123) 5'-GGGCCCCTGGCTCGGCCCCGCGG-3' (FRAG. NO:2111) (SEQ. ID NO:2124) 5'-GGGCCCCTGGCTCGGCCCCGCG-3' (FRAG. NO:2112) (SEQ. ID NO:2125) 5'-GGGCCCCTGGCTCGGCCCCGC-3' (FRAG. NO:2113) (SEQ. ID NO:2126) 35 5'-GGGCCCCTGGCTCGGCCCCG-3' (FRAG. NO:2114) (SEQ. ID NO:2127) 5'-GGGCCCCTGGCTCGGCCCC-3'(FRAG. NO:2115) (SEQ. ID NO:2128) 5'-GGGCCCCTGGCTCGGCCC-3' (FRAG. NO:2116) (SEQ. ID NO:2129) 5'-GGGCCCCTGGCTCGGCC-3' (FRAG. NO:2117) (SEQ. ID NO:2130) 5'-GGGCCCCTGGCTCGGC-3' (FRAG. NO:2118) (SEQ. ID NO:2131) 40 5'-GGGCCCCTGGCTCGG-3' (FRAG. NO:2119) (SEQ. ID NO:2132) 5'-GGGCCCCTGGCTCG-3' (FRAG. NO:2120) (SEQ. ID NO:2133) 5'-GGGCCCCTGGCTC-3' (FRAG. NO:2121) (SEQ. ID NO:2134) 5'-GGGCCCCTGGCT-3' (FRAG. NO:2122) (SEQ. ID NO:2135) 5'-GGCCCCTGGCTCGGCCCCGCGGCCCGGCTTGCCCGCCCGGCCCGG-3'(FRAG.NO:2123)(SEQ.ID NO:2136) 45 5'-GCCCCTGGCTCGGCCCCGCGGCCCGGCTTGCCCGCCCGGCCCGG-3' (FRAG. NO:2124) (SEQ. ID NO:2137) 5'-CCCCTGGCTCGGCCCCGCGGCCCGGCTTGCCCGCCCGGCCCGG-3' (FRAG. NO:2125) (SEQ. ID NO:2138) 5'-CCCTGGCTCGGCCCCGCGGCCCGGCTTGCCCGCCCGGCCCGG-3' (FRAG. NO:2126) (SEQ. ID NO:2139) 5'-CCTGGCTCGGCCCCGCGGCCCGGCTTGCCCGCCCGGCCCGG-3'(FRAG. NO:2127) (SEQ. ID NO:2140) 5'-CTGGCTCGGCCCCGCGGCCCGGCTTGCCCGCCCGGCCCGG-3' (FRAG. NO:2128) (SEQ. ID NO:2141) 50 5'-TGGCTCGGCCCCGCGGCCCGGCTTGCCCGCCCGGCCCGG-3' (FRAG. NO:2129) (SEQ. ID NO:2142) 5'-GGCTCGGCCCCGCGGCCCGGCTTGCCCGCCCGGCCCGG-3' (FRAG. NO:2130) (SEQ. ID NO:2143) 5'-GCTCGGCCCCGCGGCCCGGCTTGCCCGCCCGGCCCGG-3' (FRAG. NO:2131) (SEQ. ID NO:2144) 5'-CTCGGCCCCGCGGCCCGGCTTGCCCGCCCGGCCCGG-3' (FRAG. NO:2132) (SEQ. ID NO:2145) 5'-TCGGCCCCGCGGCCCGGCTTGCCCGCCCGGCCCGG-3' (FRAG. NO:2133) (SEQ. ID NO:2146) 55 5'-CGGCCCCGCGGCCCGGCTrGCCCGCCCGGCCCGG-3' (FRAG. NO:2134) (SEQ. ID NO:2147) 5'-GGCCCCGCGGCCCGGCTTGCCCGCCCGGCCCGG-3' (FRAG. NO:2135) (SEQ. ID NO:2148) 5'-GCCCCGCGGCCCGGCTTGCCCGCCCGGCCCGG-3' (FRAG. NO:2136) (SEQ. ID NO:2149) 5'-CCCCGCGGCCCGGCTTGCCCGCCCGGCCCGG-3' (FRAG. NO:2137) (SEQ. ID NO:2150) 5'-CCCGCGGCCCGGCTTGCCCGCCCGGCCCGG-3'(FRAG. NO:2138) (SEQ. ID NO:2151) 60 5'-CCGCGGCCCGGCTTGCCCGCCCGGCCCGG-3' (FRAG. NO:2139) (SEQ. ID NO:2152) 5'-CGCGGCCCGGCT'TGCCCGCCCGGCCCGG-3' (FRAG. NO:2140) (SEQ. ID NO:2153) 5'-GCGGCCCGGCTTGCCCGCCCGGCCCGG-3'(FRAG. NO:2141) (SEQ. ID NO:2154) WO 00/62736 PCT/USOO/08020 264 5'-CGGCCCGGCTTGCCCGCCCGGCCCGG-3' (FRAG. NO:2142) (SEQ. ID NO:2155) 5'-GGCCCGGCTTGCCCGCCCGGCCCGG-3 FRAGG. NO:2143) (SEQ. ID NO:2156) 5'-GCCCGGCTTGCCCGCCCGGCCCGG-3' FRAGG. NO:2144) (SEQ. ID NO:2157) 5'-CCCGGCTTGCCCGCCCGGCCCGG-3' (FRAG. NO:2145) (SEQ. ID NO:2158) 5 5'-CCGGCTTGCCCGCCCGGCCCGG-3' (FRAG. NO:2146) (SEQ. ID NO:2159) 5'-CGGCTrGCCCGCCCGGCCCGG-3' (FRAG. NO:2147) (SEQ. ID NO:2160) 5'-GGCTTGCCCGCCCGGCCCGG-3' FRAGG. NO:2148) (SEQ. ID NO:2161) 5'-GCTTGCCCGCCCGGCCCGG-3' (FRAG. NO:2149) (SEQ. ID NO:2162) 5'-CTTGCCCGCCCGGCCCGG-3' FRAGG. NO:2150) (SEQ. ID NO:2163) 10 5'-TTGCCCGCCCGGCCCGG-3' (FRAG. NO:2151) (SEQ. ID NO:2164) 5'-TGCCCGCCCGGCCCGG-3' FRAGG. NO:2152) (SEQ. ID NO:2165) 5'-GCCCGCCCGGCCCGG-3' FRAGG. NO:2153) (SEQ. ID NO:2166) 5'-CCCGCCCGGCCCGG-3' (FRAG. NO:2154) (SEQ. ID NO:2167) 5'-CCGCCCGGCCCGG-3' FRAGG. NO:2155) (SEQ. ID NO:2168) 15 5'-CGCCCGGCCCGG-3' FRAGG. NO:2156) (SEQ. ID NO:2169) 5'-GCCCGGCCCGG-3' (FRAG. NO:2157) (SEQ. ID NO:2170) 5'-GGCGGGGGCGGCGGCGCCTGGCTCGCCTBGGGCCCC-3' FRAGG. NO:2158) (SEQ. ID NO:2171) 5'-GGCGGGGGCGGCGGCGCCTGGCTCGCCTBGGGCCC-3 (FRAG. NO:2159) (SEQ. ID NO:2172) 5'-GGCGGGGGCGGCGGCGCCTGGCTCGCCTBGGGCC-3' (FRAG. NO:2160) (SEQ. ID NO:2173) 20 5'-GGCGGGGGCGGCGGCGCCTGGCTCGCCTBGGGC-3' FRAGG. NO:2161) (SEQ. ID NO:2174) 5'-GGCGGGGGCGGCGGCGCCTGGCTCGCCTBGGG-3' (FRAG. NO:2162) (SEQ. ID NO:2175) 5'-GGCGGGGGCGGCGGCGCCTGGCTCGCCTBGG-3' FRAGG. NO:2163) (SEQ. ID NO:2176) 5'-GGCGGGGGCGGCGGCGCCTGGCTCGCCTBG-3' (FRAG. NO:2164) (SEQ. ID NO:2177) 5'-GGCGGGGGCGGCGGCGCCTGGCTCGCCTB-3' (FRAG. NO:2165) (SEQ. ID NO:2178) 25 5'-GGCGGGGGCGGCGGCGCCTGGCTCGCCT-3' (FRAG. NO:2166) (SEQ. ID NO:2179) 5'-GGCGGGGGCGGCGGCGCCTGGCTCGCC-3' FRAGG. NO:2167) (SEQ. ID NO:2180) 5'-GGCGGGGGCGGCGGCGCCTGGCTCGC-3'(FRAG. NO:2168) (SEQ. ID NO:2181) 5'-GGCGGGGGCGGCGGCGCCTGGCTCG-3' FRAGG. NO:2169) (SEQ. ID NO:2182) 5'-GGCGGGGGCGGCGGCGCCTGGCTC-3' FRAGG. NO:2170) (SEQ. ID NO:2183) 30 5'-GGCGGGGGCGGCGGCGCCTGGCT-3' FRAGG. NO:2171) (SEQ. ID NO:2184) 5'-GGCGGGGGCGGCGGCGCCTGGC-3' (FRAG. NO:2172) (SEQ. ID NO:2185) 5'-GGCGGGGGCGGCGGCGCCTGG-3' FRAGG. NO:2173) (SEQ. ID NO:2186) 5'-GGCGGGGGCGGCGGCGCCTG-3' FRAGG. NO:2174) (SEQ. ID NO:2187) 5'-GGCGGGGGCGGCGGCGCCT-3'(FRAG. NO:2175) (SEQ. ID NO:2188) 35 5'-GGCGGGGGCGGCGGCGCC-3' FRAGG. NO:2176) (SEQ. ID NO:2189) 5'-GGCGGGGGCGGCGGCGC-3' FRAGG. NO:2177) (SEQ. ID NO:2190) 5'-GGCGGGGGCGGCGGCG-3'(FRAG. NO:2178) (SEQ. ID NO:2191) 5'-GGCGGGGGCGGCGGC-3'(FRAG. NO:2179) (SEQ. ID NO:2192) 5'-GGCGGGGGCGGCGG-3' FRAGG. NO:2180) (SEQ. ID NO:2193) 40 5'-GGCGGGGGCGGCG-3' FRAGG. NO:2181) (SEQ. ID NO:2194) 5'-GGCGGGGGCGGC-3' FRAGG. NO:2182) (SEQ. ID NO:2195) 5'-GGCGGGGGCGG-3' FRAGG. NO:2183) (SEQ. ID NO:2196) 5'-GCGGGGGCGGCGGCGCCTGGCTCGCCTBGGGCCCC-3' FRAGG. NO:2184) (SEQ. ID NO:2197) 5'-CGGGGGCGGCGGCGCCTGGCTCGCCTBGGGCCCC-3' FRAGG. NO:2185) (SEQ. ID NO:2198) 45 5'-GGGGGCGGCGGCGCCTGGCTCGCCTBGGGCCCC-3' FRAGG. NO:2186) (SEQ. ID NO:2199) 5'-GGGGCGGCGGCGCCTGGCTCGCCTBGGGCCCC-3' FRAGG. NO:2187) (SEQ. ID NO:2200) 5'-GGGCGGCGGCGCCTGGCTCGCCTBGGGCCCC-3'(FRAG. NO:2188) (SEQ. ID NO:2201) 5'-GGCGGCGGCGCCTGGCTCGCCTBGGGCCCC-3' FRAGG. NO:2189) (SEQ. ID NO:2202) 5'-GCGGCGGCGCCTGGCTCGCCTBGGGCCCC-3' FRAGG. NO:2190) (SEQ. ID NO:2203) 50 5'-CGGCGGCGCCTGGCTCGCCTBGGGCCCC-3' FRAGG. NO:2191) (SEQ. ID NO:2204) 5'-GGCGGCGCCTGGCTCGCCTBGGGCCCC-3'(FRAG. NO:2192) (SEQ. ID NO:2205) 5'-GCGGCGCCTGGCTCGCCTBGGGCCCC-3' (FRAG. NO:2193) (SEQ. ID NO:2206) 5'-CGGCGCCTGGCTCGCCTBGGGCCCC-3' FRAGG. NO:2194) (SEQ. ID NO:2207) 5'-GGCGCCTGGCTCGCCTBGGGCCCC-3' FRAGG. NO:2195) (SEQ. ID NO:2208) 55 5'-GCGCCTGGCTCGCCTBGGGCCCC-3' FRAGG. NO:2196) (SEQ. ID NO:2209) 5'-CGCCTGGCTCGCCTBGGGCCCC-3' FRAGG. NO:2197) (SEQ. ID NO:2210) 5'-GCCTGGCTCGCCTBGGGCCCC-3' FRAGG. NO:2198) (SEQ. ID NO:221 1) 5'-CCTGGCTCGCCTBGGGCCCC-3' FRAGG. NO:2199) (SEQ. -ID NO:2212) 5'-CTGGCTCGCCTBGGGCCCC-3' FRAGG. NO:2200) (SEQ. ID NO:2213) 60 5'-TGGCTCGCCTBGGGCCCC-3' FRAGG. NO:2201) (SEQ. ID NO:2214) 5'-GGCTCGCCTBGGGCCCC-3'(FRAG. NO:2202) (SEQ. ID NO:2215) 5'-GCTCGCCTBGGGCCCC-3'(FRAG. NO:2203) (SEQ. ID NO:2216) WO 00/62736 PCT/USOO/08020 265 5'-CTCGCCTBGGGCCCC-3' (FRAG. NO:2204) (SEQ. ID NO:2217) 5'-TCGCCTBGGGCCCC-3' (FRAG. NO:2205) (SEQ. ID NO:2218) 5'-CGCCTBGGGCCCC-3' (FRAG. NO:2206) (SEQ. ID NO:2219) 5'-GCCTBGGGCCCC-3' (FRAG. NO:2207) (SEQ. ID NO:2220) 5 5'-CCTBGGGCCCC-3' (FRAG. NO:2208) (SEQ. ID NO:2221) 5'-CTBGGGCCCC-3' (FRAG. NO:2209) (SEQ. ID NO:2222) 5'-GGGTGGGCBCGGCGGCC-3' (FRAG. NO:2210) (SEQ. ID NO:2223) 5'-GGTCGGCGBBGBGCTCGTCGTGGC-3' (FRAG. NO:2211) (SEQ. ID NO:2224) 5'-GGTCGGCGBBGBGCTCGTCGTGG-3 (FRAG. NO:2212) (SEQ. ID NO:2225) 10 5'-GGTCGGCGBBGBGCTCGTCGTG-3' (FRAG. NO:2213) (SEQ. ID NO:2226) 5'-GGTCGGCGBBGBGCTCGTCGT-3' (FRAG. NO:2214) (SEQ. ID NO:2227) 5'-GGTCGGCGBBGBGCTCGTCG-3' FRAGG. NO:2215) (SEQ. ID NO:2228) 5'-GGTCGGCGBBGBGCTCGTC-3' FRAGG. NO:2216) (SEQ. ID NO:2229) 5'-GGTCGGCGBBGBGCTCGT-3' (FRAG. NO:2217) (SEQ. ID NO:2230) 15 5'-GGTCGGCGBBGBGCTCG-3' FRAGG. NO:2218) (SEQ. ID NO:2231) 5'-GGTCGGCGBBGBGCTC-3' FRAGG. NO:2219) (SEQ. ID NO:2232) 5'-GGTCGGCGBBGBGCT-3' FRAGG. NO:2220) (SEQ. ID NO:2233) 5'-GGTCGGCGBBGBGC-3' (FRAG. NO:2221) (SEQ. ID NO:2234) 5'-GGTCGGCGBBGBG-3' FRAGG. NO:2222) (SEQ. ID NO:2235) 20 5'-GGTCGGCGBBGB-3' (FRAG. NO:2223) (SEQ. ID NO:2236) 5'-GGTCGGCGBBG-3' FRAGG. NO:2224) (SEQ. ID NO:2237) 5'-GTCGGCGBBGBGCTCGTCGTGGC-3' FRAGG. NO:2225) (SEQ. ID NO:2238) 5'-TCGGCGBBGBGCTCGTCGTGGC-3' (FRAG. NO:2226) (SEQ. ID NO:2239) 5'-CGGCGBBGBGCTCGTCGTGGC-3' (FRAG. NO:2227) (SEQ. ID NO:2240) 25 5'-GGCGBBGBGCTCGTCGTGGC-3'(FRAG. NO:2228) (SEQ. ID NO:2241) 5'-GCGBBGBGCTCGTCGTGGC-3' FRAGG. NO:2229) (SEQ. ID NO:2242) 5'-CGBBGBGCTCGTCGTGGC-3' FRAGG. NO:2230) (SEQ. ID NO:2243) 5'-GBBGBGCTCGTCGTGGC-3' FRAGG. NO:2231) (SEQ. ID NO:2244) 5'-BBGBGCTCGTCGTGGC-3' FRAGG. NO:2232) (SEQ. ID NO:2245) 30 5'-BGBGCTCGTCGTGGC-3' FRAGG. NO:2233) (SEQ. ID NO:2246) 5'-GBGCTCGTCGTGGC-3' FRAGG. NO:2234) (SEQ. ID NO:2247) 5'-BGCTCGTCGTGGC-3' FRAGG. NO:2235) (SEQ. ID NO:2248) 5'-GCTCGTCGTGGC-3' FRAGG. NO:2236) (SEQ. ID NO:2249) 5'-CTCGTCGTGGC-3' FRAGG. NO:2237) (SEQ. ID NO:2250) 35 5'-TCGTCGTGGC-3' (FRAG. NO:2238) (SEQ. ID NO:2251) 5'-GGGGCCCCGCGCCGCCCGCC-3' FRAGG. NO:2239) (SEQ. ID NO:2252) 5'-GGGGCCCCGCGCCGCCCGC-3' FRAGG. NO:2240) (SEQ. ID NO:2253) 5'-GGGGCCCCGCGCCGCCCG-3' FRAGG. NO:2241) (SEQ. ID NO:2254) 5'-GGGGCCCCGCGCCGCCC-3'(FRAG. NO:2242) (SEQ. ID NO:2255) 40 5'-GGGGCCCCGCGCCGCC-3'(FRAG. NO:2243) (SEQ. ID NO:2256) 5'-GGGGCCCCGCGCCGC-3' FRAGG. NO:2244) (SEQ. ID NO:2257) 5'-GGGGCCCCGCGCCG-3' FRAGG. NO:2245) (SEQ. ID NO:2258) 5'-GGGGCCCCGCGCC-3' FRAGG. NO:2246) (SEQ. ID NO:2259) 5'-GGGGCCCCGCGC-3' FRAGG. NO:2247) (SEQ. ID NO:2260) 45 5'-GGGCCCCGCGCCGCCCGCC-3'(FRAG. NO:2248) (SEQ. ID NO:2261) 5'-GGCCCCGCGCCGCCCGCC-3' FRAGG. NO:2249) (SEQ. ID NO:2262) 5'-GCCCCGCGCCGCCCGCC-3' FRAGG. NO:2250) (SEQ. ID NO:2263) 5'-CCCCGCGCCGCCCGCC-3' FRAGG. NO:2251) (SEQ. ID NO:2264) 5'-CCCGCGCCGCCCGCC-3' FRAGG. NO:2252) (SEQ. ID NO:2265) 50 5'-CCGCGCCGCCCGCC-3' FRAGG. NO:2253) (SEQ. ID NO:2266) 5'-CGCGCCGCCCGCC-3' FRAGG. NO:2254) (SEQ. ID NO:2267) 5'-GCGCCGCCCGCC-3' FRAGG. NO:2255) (SEQ. ID NO:2268) 5'-CGCCGCCCGCC-3' FRAGG. NO:2256) (SEQ. ID NO:2269) 5'-GCCGCCCGCC-3' FRAGG. NO:2257) (SEQ. ID NO:2270) 55 5'-GGGGCGCGCGGGGCCGCCGGG-3'(FRAG. NO:2258) (SEQ. ID NO:2271) 5'-GGCGGGGBGCGGCBGGGCCCGGGCCC-3'(FRAG. NO:2259) (SEQ. ID NO:2272) 5'-GGCGCGTCGCCGTCGCCCCBGTCGGGCTCGCGC-3' FRAGG. NO:2260) (SEQ. ID NO:2273) 5'-GCGCGGGCBBCBGCGBGCCGGGCGCG-3'(FRAG. NO:2261) (SEQ. ID NO:2274) 5'-GCGCBCGGGCCCBCCTGCGCGGGC-3 FRAGG. NO:2262) (SEQ. ID NO:2275) 60 5'-GGGCGGGGTGGGCTGCCCTGCGGCCGCC-3'(FRAG. NO:2263) (SEQ. ID NO:2276) 5'-GGGCTGCTGCGCGGCGGCTCCGGCGA-3' FRAGG. NO:2264) (SEQ. ID NO:2277) 5'-CTCCCGGGCGGGGCCGGGCGCGGGG-3' FRAGG. NO:2265) (SEQ. ID NO:2278) WO 00/62736 PCT/USOO/08020 266 5'-GGGCTGCCGCGGTCCGGGCCCCTCTTGCCGGCG-3' (FRAG. NO:2266) (SEQ. ID NO:2279) 5'-GCGCTCGCGCCGCTGCCGG-3' (FRAG. NO:2267) (SEQ. ID NO:2280) 5'-GCGCCGCTTGGCCTTGTCGCGGC-3' (FRAG. NO:2268) (SEQ. ID NO:2281) 5'-GCTGCTCCBCGCGCTGG-3' (FRAG. NO:2269) (SEQ. ID NO:2282) 5 5'-GCCGGBGGCCGGCCBGGTCCCGCG-3' (FRAG. NO:2270) (SEQ. ID NO:2283) 5'-CCCGGCGGCCGGCBGGBBGGGCGGGCTGGGC-3' (FRAG. NO:2271) (SEQ. ID NO:2284) 5'-GTCTCTCCCGCCCCGGCCGCGCG-3' (FRAG. NO:2272) (SEQ. ID NO:2285) 5'-GGGCGTCCGCTCCGGGCCGTCGGG-3 (FRAG. NO:2273) (SEQ. ID NO:2286) 5'-GCGGGCACGCGGCGGCTCTGGCGTCGGC-3' (FRAG. NO:2274) (SEQ. ID NO:2287) 10 Bradykinin Receptor Nucleic Acids and Antisense Oligonucleotide Fragments 5'-GGTGBCBTTG BGCBTGTCGG CGCGGTCCCG TTBBGBGTGG GCCCGCCAGC CCAGCCACTC CACTTGGGGG CGGGTGGCCA GCACGAACAG CACCCAGAGG AAGGGGGGCG GCCCAGAAGG GCAGCCCGCA GGCCAGGATC AGGTCTGCTG CGGCCGGAGA TAATGGCATT CACCACGCGG CGGCCCAGCG CACGCCGCGC ATCCGGCCCG GGTTCTGACC TGCAGCCCCC GTCTCCTTGG CATTCCTGGG CCCCAGTCAC TCCTCTCCCT GCCCCCCTTG 15 CTGGGGCAGG GACGGGGTG BCBTTGBGCB TGTCGGCGCG GTCCCGTTBB GBGTGGGCCC GCCAGCCCAG CCACTCCACT TGGGGGCGGG TGGCCAGCAC GAACAGCACC CAGAGGAAGG GGGGCGGCCC AGAAGGGCAG CCCGCAGGCC AGGATCAGGT CTGCTGCGGC CGGAGATAAT GGCATTCACC ACGCGGCGGC CCAGCGCACG CCGCGCATCC GGCCCGGGTT CTGACCTGCA GCCCCCGTCT CCTTGGCATT CCTGGGCCCC AGTCACTCCT CTCCCTGCCC CCCTTGCTGG GGCAGGGACG GCCGTGTTGT CBGTGGTGCT GCCCGTTTGB GGTBTGGCGC 20 TCCBCCBBTT CCCTTTTCTC CTTGTTTTCC GTTTCTCTTG CCGTCTGTGG TT CAGATTCACA AACTGCAGGA CTGGGCAGGG AGCAGACAGT GAGCAAACGC CAGCAGGGCT GCTGTGAATT TGTGTAAGGA TTGAGGGACA GTTGCTTTC AGCATGGGCC CAGGAATGCC AAGGAGACAT CTATGCACGA CCTTGGGAAA TGAGTTGATG TCTCCGGTAA AACACCGGAG ACTAATTCCT GCCCTGCCCA ATTTTGCAGG GAGCATGGCT GTGAGGATGG GGTGAACTCA CGCACAGCCA AGGACTCCAA AATCACAACA GCATTACTGT TCTTATTTGC TGCCACACCT 25 GAGCCAGCCT GCTCCTTCCC AGGAGTGGAG GAGGCCTGGG GGGAGGGAGA GGAGTGACTG AGCTTCCCTC CCGTGTGTTC TCCGTCCCTG CCCCAGCAAG ACAACTTAGA TCTCCAGGAG AACTGCCATC CAGCTTTGGT GCAATGGCTG AGTGCACAAG TGAGTTGTTG CCCTGGGTI7 CTTTAATCTA T7CAGCTAGA ACTTTGAAGG ACAATTTCTT GCATTAATAA AGGTTAAGCC CTGAGGGGTC CCTGATAACA ACCTGGAGAC CAGGATTTTA TGGCTCCCCT CACTGATGGA CAAGGAGGTC TGTGCCAAAG AAGAATCCAA TAAGCACATA TT1GAGCACT7 30 GCTGTATATG CAGTATTGAG CACTGTAGGC AAGACCCAAG AAAGAGAAGG AGCCATCTCC ATCTTGAAGG AACTCAAAGA CTCAAGTGGG AACGACTGGG CACTGCCACC ACCAGAAAGC TGTTCGACGA GACGGTCGAG CAGGGTGCTG TGGGTGATAT GGACAGCAGA AGGGGGAGAC CAAGGTTCCA GCTCAACCAA TAACTATTGC ACAACCACCT GTCCCTGCCT CAGTTCCCTT TTATGTAACA TGAAGTCGTT GTGAGGGTTA AAGGCAGTAA CAGGTATAAA GTACTTAGAA AAGCAAAGGG TGCTACGTAC ATGTGAGGCA TCATTACGCA GACGTAACTG 35 GGATATGTTT ACTATAAGGA AAAGACACTG AGGTCTAGAA ATAGCTCCGT GGAGCAGAAT CAGTATTGGG AGCCGGTGGC GGTGTGAAGC ACCAGTGTCT GGCACACAGT AGGTGCTCAT TGGCTCCCTT CCACCTGTCA TTCCCACCAC CCTGAGGCCC CAACCGCCAC ACACACAGGA GCATTTGGAG AGAAGGCCAT GTCT7CAAAG TCTGATTTGT GATGAGGCAG AGGAAGATAT TTCTAATCGG TCTTGCCCAG AGGATCACAG TGCTGAGACC CCCCACCACC AGCCGGTACC TGGGAAGGGG GAGAGTGCAG GCCTGCTCAG GGACTGTTCC TGTCTCAGCA 40 ACCAAGGGAT TGTTCCTGTC AATCAATGGT TTATTGGAAG GTGGCCCAGT ATGAGCCCTA GAAGAGTGTG AAAAGGAATG GCAATGGTGT TCACCATCGG CAGTGCCAGG GCAGCACTCA TTCACTTGAT AAATGAATAT TTATTAGCTG GTTGGAGAGC TAGAACCTGG AGAGCTAGAA CCTGGAGAAC TAGAACCTGG AGGGCTAGAA CCTGGAGAGG CTAGAACCAA GAAGGGCTAG AACCTGGAGG GGCTAGAACC TAGAGAAGCT AAAACCTGAG CTAGAAGCTG GAGGACTAGA ACCTGGAGGG CTGGAATCTG AAGGGCTAGA ACCTGGAGGG CTGGAATCTG 45 GAGAGCTAGA ACCTGGAGGG CTAGAACCTG GAGGGCTAGA ACCTAGAAGG GCTAGAACCT GGAGGGCTGG AATCTGGAGA GCTAGAACCT GGAGGGCTAG AACCTGGAGG GCTAGAACCT AGAAGGGCTA GAACCTGGAG GGCTAGAACC TGGCAGGTTA GAACCTAGAA GGGCTAGAAC CTGGAGAGCC AGAACCTGGA GGGCTAGAAC CTGGAAGGGC TAGAACCTGT AGAGCTAGAA CATGGAGAGC TAGAACCCGG CAGGCTAGAA CCTGGCAAGC TAGAACCTGG AGGGAATGAA CCTGGAGGGC TAGAACCTGG AGAATGAGAA AAATACAT GGCAAAGAGC 50 CCATAAATCC TGACCAATCC AACTCTGAAT TTTAAAGCAA AAGCGTGAAA AAAAAGATTC CCTCCTTACC CCCAACCCAC TCTTTTTTCC CACCACCCAC TCTCCTCTGC CTCAGTAAGT ATCTGGAGGA AGAAAACAGG TGAAAGAAGA AGTAAAAACC ATTTAGTATT AGTATTAGAA TGAAGTCAAA CTGTGCCACA CATGGTGAAT GAAAAAAAAA AAAAAGAGGC TGTGTTGT CACACAGGGC AGTCATTCAG CACCAGAGCA CGTGATGGTC TGAGACTCTC TTAGGAGCAG AGCTCTGCCG CAATGGCCAT GTGGGGATCC ACACCTGGTC TGAGGGGCAA 55 CTGAGTCTGC GGGAGAAGAG CGGCCCTATG CATGGTGTAG ATGCCCTGAT AAAGAACATC TGTCCTGTGA AAGACTCAAT GAGCTGTTAT GTTGTAAACA GGAAGCATTT CACATCCAAA CGAGAAAATC ATGTAAACAT GTGTC'TTTC TGTAGAGCAT AATAAATGGA TGAGGTTTTT GCAAAAAAAA AAAAAAAAA AAATGATAGA CCGTCAATAA TTTGTTAAAT GC11TIrAAA ATGAATGCTT TAAGCCGGGT GCAGTGCCTC ACATCTGTAA TCCCAGCACT TTGGAGCCGA GCGGGTGGAT TGTGTGAGGT CAGGAGTTCG AGACCAACCT GGCCAACATG 60 GCAAAACCTC ACTCTCTACC AAAAATACAA AAATTAGCCA GGCATGGTGG CAGGCACCTG TGATCCCAGC TACTCAGGAG GCTGAGACAG GAGAATCGCT TGAACCCGGG AGGCAAGGTT GCAGTGAGCC AAGATTACGC CATTGTACTC CAGCCTGGGT GACAGAGAGA GACTCCGTCT CAAAAAAAAA AAAAAAAAAA AAAAAATTAC GCTTCAAACA CATGATCTCT CACCACTGTT GAATTCTT TCTATGAGCC CAGGAGGGCC TCTCAGAGAG GAAAGCTCCT AGGTCTTCCT TTCCCTCTGC AAACTCCCTG CCTTGAAGGT TCAGAAGGAC TGTGCGTGCT 65 CGTTGCATCC TTTGCAAGTG TCCAAACCCT GATCCCAGCT GTGCTTAGGG GTTCCTGCAA ACCTTTTCCA WO 00/62736 PCT/USOO/08020 267 GGTGTTAArT ACCTCCCACT TCATTTCCTG TTTACCAACT CAGCTTTTTG TTTTAGTGTG TTTGAATTCC CTGAACTGAC CGTTGTCTGA TCTCCACCTC CCAACTGAAT TAGGGGAGCT GGGCTrCTGG AAACCCAGGT GCCGGGTGTT GCAGAGTGGC TGAAAGCTGG GATGTGGCAG ATCCGTGGCT ACATTCATGC ACACACACAC ACCCACATAC CCACACATGC ACACACACAC ACACACCCGC ACTCACACAC TTGGACATGC ATAGACCACA 5 GCTTTCCACA CCCTTCCTAG ACAGGGGTCA CTTGGTATCC TGGAGAGAGT GTGAAGTCCT GGAATGGAAA GAGGGGGGAT TAAGCCCCAC CTCTAGCCAT GGGACTGAGA CAAGTCACCA CCAACCCATC TGCGCCTTGT TTACCTCCTC TGTGAGGCAA GCACAGAGCC CATGCCTGCC CCCCTGGATG GGAGTGATGT GAAACTTGAA GGGCGGTCAG AGCAAGGGTC GGGAATGGAA GGCCCT'GGG AAAAAAGGCC CTTTCAACTA GGGGCACAGA GGAGGCCCTG GGCTGAGAAC TTGACAGCAC CTTGTAATTG GTAAGCCAAG CCCGAAGGGA CTGGAAATAC 10 TCAGATGTGT CTGTCTCCCT TATTAGGTTC AAAGTCCCTC AAGACCCTGT CTCCATCACA GTGCTCCAGT CCAGACCCCT CCTCTGAGCT CCAGACCCTG CTGGACCCAA CCAGCCCTAT GGGGTCGCAT CCCCACCTGC CTGGAATTCT CCAAAGAACC TCCCCTTTAA CAGTTCCAGC CITAACAGT TCCAGTCTAA ACACATGACC TTTCTCCTCT AAATCAGCCC CCCATCTCTG CCTTTGCAGG AGATGGAAGC CATGACACCT GCCTCGCCCC TGTCCTCACC CCATCCATGT CCAATCAAGC ACTAGGCATG TCAGGTTTAC CCTCTAAACT CCTCTGGAAT 15 CCAGTCTCTC AGTCTCCATC ATCCCAGGTC GAAGCTAATG GGCTAACTGG TCCTTGCTTC CACTCTACCC CCACTGCAGT CCTGACTTCC TGAGCAGCAG CCAGGGCCTA ATCGATATTC ACACCAAGCG CCAACCTGAC TGAGATATCC TCCTGCACCA TCATCCCTCC ACCCTGTTTA GTTCTGCTCA CCCTCAGTGT TCTCATCAAT AATCCACTCC CCTCACAGGC GCGTTTGGGA CCCCATGTTC TATGCTCTCA CAGGACCTTT TGCTrGATTT TTCACTGTAC TTAGGTCAGT TTGCAGTTAT TAAGTGACTG AGCAATGTCT GGCTTCTCCA GTAGACTGTC 20 AGCTCCTAGC CATTGTATAC CTAGCACCGC TGTGTGGGAG CACGTGACAA ACGTCCAGTG AGTCAGGGAC TCAGCAGTCT CCATTTCTCC GCCCTGCTGG AGAATGCGTG TATTTGGCAA TCCCCAGCCC CTGTGCCATC TAACCATCTT TTCTTCTCTG TTCAGCCCAG GTGTGGCCTC ACTCACATCC CACTCTGAGT CCAAATGTTC TCTCCCTGGA AGATATCAAT GTTTCTGTCT GTTCGTGAGG ACTCCGTGCC CACCACGGCC TCTTTCAGGT GAGTCAAAGG GATTCCTCAG TTCACTAGTT AGGGGAGGTG GGCAGACACC CTGGAGAACT CCCTGGAAAG 25 CTCAACTCTC ATGCCCCGGA CAACAGTTGA AGGAACCATG GTGATGTTAA GCCCAAAGAC AAAACCTCTC AGGTGTCCAA GTCCCTGTTG GAATCTGGG AGCAGAGGGA ATGTTCTGTG GTCTAGAGGA AGAGGGGCTC AGGGAGGAGA AGGGCACATT CCTGGTTGTT ATATGTTTCT ATCTATCCCA GATGAACTTG GAAGTGAAGG GAAGAGAGTT AAACATTAAA GTAAATACCC AGTGGATCAG ACAGCAATGT GCCAGATTGC CTTGGAAACA AAATATCTCC AACACATGGC TGACATTTGG TGGGAGATCA GAACACCCTA AAGAGAGAAT TTAAGGGGAG 30 GGGGAGGAGG ACCTGAGCCA GAGTAGAAGC AGAGGATAGG GAGATCTGTT CTTGGGGACA GCATTTGCAA GAAACAAGGC TGAGGGGTCC ACTCCAACCT CTCCACCCTG CTGCAGGTGC TGCCTATGAT GAAGATGAGC AGATGGCCAT CTCAGCTGGG GCCACAGTGC ACTGGACCTA TAGTTTCCAA TTCCGCACTC AGCAGGCATC TTTCTGATGA TCCGATGGCT TCTCAGAGCC AGGGATGGGC CAGGATCCAT CCCCTTGGCT ACTGTCTTGC TGAGAAATTT ATAAGCAGCA TCTGGTGCTA TACTTTGGTC TCTAGTGAGT TAGCTCATGA AAGATGATAG 35 ACTCTCCAAG CCAGGGGTAT GCAGGAAATG GGTTTTCTGT AGCTACAGAA ATGGGGTTGA GGGTTGGACC AAGGGACTAC CCAGGGGAAG TCTTACCTrC AGAGGACTCT GGAAAGGAGG CTGCAAGTTT TCATGGGTCA AGAATTCAGA GCCCAGTAGA GACAGCTTAT CTCTGTTCCA AGATGTCTGG GGCCTTGGTT GGAAGATTCA AAGGCTAGGA AACCAGGAGC CACCAAAAGC GTAACTGGGG CCAGAGGATC CACTTTCAAG GTGGCAAGTr GGTTCCCCCC ATGTGGCTGC TTGAGTATCC TCACATGGCG GCTCACATCC TTCCAAGTAA GCAATGCAAA 40 AGGCCAAGAA AGATGCTGCA AAGATGTTAT GACCTAGCCT CAGAAATCAC ACACCATCCC TGCCACCATT AGTAAGAAGT CCAGCCCACG TCCAGGAGAA GAGGAAGCAG ATTCCTCCTT TTGAAATGAA GAATATCAAG TAATTCGGGG GGCATATGAA AGCCACCACA CACCACAGGG ATCTTTTTAG AGCATACTTC TTATACCATC ACTGTAGTTC CTTAAGACTC AGGGGCAAAG CCTCACTTCC TTAGCACCCA GTGAAGACCA CGCTTACTCC CTCACTCAAC CTCTTGCTAC TTCCCACCTC TCCTGTCCAA CATCTAGTGT CACTCCAG AACATACCAA 45 CAGCTTCCCC AGTTCTGTGC CTCTGCTCAG GCTGTTCCCC CTGCCTGGTC CACTTGTCCT CCTTCTTGTC CGGTCAAAAT GCTTCTTATC CTTCAAGACC CAGCTCTAGA GTCACCTCCA ACCCCTTACC CACCAGCCCC CTCTCCAAGT CTGTGTCCCA CAACCCCCCT GCTCCCTCCA GGGCACCCTC CACCCTCTGG GCCACAGTTG TCAGGAGTCA GGCAGGGCAG GGGCCGGGTG GTGTCTTCTT TGTGTTCTTG CACTCAGGGC AGAGCTCAGC ACAGAGCAGA CGCTCAAAAA ACATTTAAAG GATAGAAGCA TTGATTTGTG GGTCCCCCAG TCTGGCTCCA 50 GGATGCCAGC CAGCTGCTCC TAGAAGCAAA CGGACTTTTC CTGGGAAATC CCAGAGGTGA TGATCAGTAA TCTCTCCCGT GACTCGTAGT TCAGCTCTTC CTCCATGAGC CTGACTATCA GTGGACCTTC CAGAAAGAGC CCCTTTTCCT TCTCTCACCC ACAGCACAGG GCACTGGGAA AATGCCCAAT GAGTCCTGCC TCTGGGTTGT GCTTTGGACT TTTCAGTGTG TCTCGCATCC ACTCTTCAAC TTGAATGTTG CAACAGCCAT GAAAAAAGAA ATGCAAAGCG ATrCAGGATG AGAGCAATAC CCTACTCCAA AGAAGGCAAC ATAGAAGCTC AGAGAGATCA 55 AGCAATTTGC CCAAGACCAC ACAGCTAGGA GTGGAACTCA TGGCTGTCCA AGCCCCATGC CTCTGCTGAA GGTAGAGATG AATTACAGCA ACAAGTCTAG AAAGGTGCCT GCCCTATGGT CTGTGAGTCT TGCCTAAGAA TGAAAGAGGA GCCAGTGGGT TAAAGATGAG GTCACCAACA ACGGTGGTGT TGGAGTTT7AC CACTGATAAT AAGGGTGCAA AATGTAAATTr ACTAATGTTT ATTGAGCCTA GTGCAGTGCG TGGGGCATTT TGCACATTGT CTCTGATCCC TATGACAACC CTGAGAGGTA GTGGTTTTAA CTGCCATGTT ACAGGTGAGG TCATTGTGGT 60 TCAAGGACGT TAAGTAACTT CCCCAGCGTG ACACGGCTTA TAAGTAAGGC AGCCAGGATG TGAACCCAGT AGGACTATCT GGCTGCAAAG TCCCCACCCC CCTCGCCATC TGTATCCTCC AATCACTTCA GTGCTTTGCT GCATAGAAGG TAACGGAAAT CACGATGCCA CAGACTGTCC AGGAAGACAG AAACTAGGCA GATGGGCTGG CCATGGTCTC CAAGCCAGAC TGGAATCTCC AGGTCTGGAA TGATATCATT TTTCTCTTTT AATAAATTAA CTCACCCACC ACACGGCTTT GAGAGGCTCA AAGTTGACCA ACTCCCTTGG GAGGGCCCCG GTTGATAAGG 65 AAGGAACGTG AATCCTCCCA TCACGGAAGC TTCAAGGAGG TCAAGGGTCC AACACTTGAG ATTGTTAGTG CTGTTGGTGG ATACTGGCCA AGGAAATATC CCAGTGGAGC CTCGAGATGA AGAACATGAG GCCCCCGTTT WO 00/62736 PCT/USOO/08020 268 AGAACCAAGG ATCAGAGGGG GCTCTGTAAG ACCCAGGGGA GTCAGGTGCA CTGGAGCGCG GGCATGCAGA AAACAGCCTG AGCTCCACCT CGGCTTCTCC TTGTCCTGGC TGGTTGTCCT TAACCCCTGT CTCCTTCTGG ACCAGTTT GTCCTTCCCT TGTGACCGCT GAGGGGTAAC AGCCTCTTTC CACTTTCTTT CAGCGCCGAC ATGCTCAATG TCACCTTGCA AGGGCCCACT CTTAACGGGA CCTTTGCCCA GAGCAAATGC CCCCAAGTGG 5 AGTGGCTGGG CTGGCTCAAC ACCATCCAGC CCCCCTTCCT CTGGGTGCTG TTCGTGCTGG CCACCCTAGA GAACATCTTT GTCCTCAGCG TCTTCTGCCT GCACAAGAGC AGCTGCACGG TGGCAGAGAT CTACCTGGGG AACCTGGCCG CAGCAGACCT GATCCTGGCC TGCGGGCTGC CCTTCTGGGC CATCACCATC TCCAACAACT TCGACTGGCT CTTFGGGGAG ACGCTCTGCC GCGTGGTGAA TGCCATTATC TCCATGAACC TGTACAGCAG CATCTGTTTC CTGATGCTGG TGAGCATCGA CCGCTACCTG GCCCTGGTGA AAACCATGTC CATGGGCCGG 10 ATGCGCGGCG TGCGCTGGGC CAAGCTCTAC AGCTTGGTGA TCTGGGGGTG TACGCTGCTC CTGAGCTCAC CCATGCTGGT GTrCCGGACC ATGAAGGAGT ACAGCGATGA GGGCCACAAC GTCACCGCTT GTGTCATCAG CTACCCATCC CTCATCTGGG AAGTGTrCAC CAACATGCTC CTGAATGTCG TGGGCTTCCT GCTGCCCCTG AGTGTCATCA CCTTCTGCAC GATGCAGATC ATGCAGGTGC TGCGGAACAA CGAGATGCAG AAGTTCAAGG AGATCCAGAC GGAGAGGAGG GCCACGGTGC TAGTCCTGGT TGTGCTGCTG CTATTCATCA TCTGCTGGCT 15 GCCCTTCCAG ATCAGCACCT TCCTGGATAC GCTGCATCGC CTCGGCATCC TCTCCAGCTG CCAGGACGAG CGCATCATCG ATGTAATCAC ACAGATCGCC TCCTTCATGG CCTACAGCAA CAGCTGCCTC AACCCACTGG TGTACGTGAT CGTGGGCAAG CGCTTCCGAA AGAAGTCTTG GGAGGTGTAC CAGGGAGTGT GCCAGAAAGG GGGCTGCAGG TCAGAACCCA TTCAGATGGA GAACTCCATG GGCACACTGC GGACCTCCAT CTCCGTGGAA CGCCAGATTC ACAAACTGCA GGACTGGGCA GGGAGCAGAC AGTGAGCAAA CGCCAGCAGG GCTGCTGTGA 20 ATTTGTGTAA GGATTGAGGG ACAGTTGCTT TTCAGCATGG GCCCAGGAAT GCCAAGGAGA CATCTATGCA CGACCTTGGG AAATGAGTTG ATGTCTCCGG TAAAACACCG GAGACTAATT CCTGCCCTGC CCAATTTTGC AGGGAGCATG GCTGTGAGGA TGGGGTGAAC TCACGCACAG CCAAGGACTC CAAAATCACA ACAGCATTAC TGTTCTTATT TGCTGCCACA CCTGAGCCAG CCTGCTCCTT CCCAGGAGTG GAGGAGGCCT GGGGGCAGGG AGAGGAGTGA CTGAGCTTCC CTCCCGTGTG TTCTCCGTCC CTGCCCCAGC AAGACAACTT AGATCTCCAG 25 GAGAACTGCC ATCCAGCTTT GGTGCAATGG CTGAGTGCAC AAGTGAGTTG TTGCCCTGGG TTrCTTTAAT CTATTCAGCT AGAACTTTGA AGGACAATTT CTTGCATTAA TAAAGGTTAA GCCCTGAGGG GTCCCTGATA ACAACCTGGA GACCAGGATT TTATGGCTCC CCTCACTGAT GGACAAGGAG GTCTGTGCCA AAGAAGAATC CAATAAGCAC ATATTGAGCA CTTGCTGTAT ATGCAGTATT GAGCACTGTA GGCAAGAGGG AAGAAAGAGA AGGAGCCATC TCCATCTTGA AGGAACTCAA AGACTCAAGT GGGAACGACT GGGCACTGCC ACCACCAGAA 30 AGCTGTTCGA TGAGACGGTC GAGCAGGGTG CTGTGGGTGA TATGGACAGC AGAAGGGGGA GCCAGGTTCC AGCTCACCAA TACTATTGCA CACCACCTGT CCTGCCTC GCCCTTCAAA GATGAGCTGT TCCCGCCGCC ACTCCAGCTC TGGCTTCTGG GCTCCGAGGA GGGGTGGGGA CGGTGGTGAC GGTGGGGACA TCAGGCTGCC CCGCAGTACC AGGGAGCGAC TGAAGTGCCC ATGCCGCTTG CTCCGGAGAA GGTGGGTGCC GGGCAGGGGC TGCTCCAGCC GCCTCACCTC TGCTGGGAGG ACAAACTGTC CCAGCACAGA GGGAGGGAGG GAGGGCAGGC 35 AGCGGGGAGA AGTTTCCCTG TGGTCGTGGG GAGTT GAGCTCTTCA ATATTTTAGT GAAAGCTATA GATGAGGCTC CATAGGGGAT AAAGCACAGA CACACCTT CAGAGGGCTT GTGGACTCTG GGCAGCCTGT CCATAGACCT CTGTCCCCAA CTGGCAAGTC AGGAAACTCC AGATTAAGGA GCCCCAATGT GGTTGAACAG CCAGGTGCAC AGATGAGTCA ACCACACAGC CAGGCCAGGG AGGGCCTTCA CTCAAGAGCC TACAGCCAGT TCACAGCCAA GCCAGGGCTA GCGCCAGGCC ACCCATAAAC TGATCTGAGA CTCTGTTTCC CTGTCTCCAT 40 GATGATGGGA TCAGGCTTGA TTGCTGGTTT GTAGGCTTGT TATGAATCAA GTCACAGGGA AGAGGAGCTG ATGGGCTGGG GGGACGTCCT CTGGCCCTCC TGTCTCTTCC CCAGATCCAC TGGGCCCACT CTTATCTGTT CTCTTCTGAA GGAAGGGTTT TAAGGCTTCA AAAAAAAATG TTTGAAAGT CCCTGCCCTT TCCAGCTCCT ACCGTCTCAG CCCTGGGAGT GTAAAGTGCT GCAGATAGTT AGTAAGTCT TGAGCAAAAC TGAGAAAGCC AGCCTGAGCC TTGACATGGG AGAAACCTCC GCCATACATC TCCGAAGAAA CGGCCGCGTG TCTCAGGGGA 45 GCGCAAACAC CCGTACCCAG GAAACAGGAC AGCTTCTGCC ACTGTCGCCC TTGGGAGCCG TACGTGGCAT GACAAAGAAA TCCCAGGACT CCGCCTGCCC ACCTGGCCAC CCTCTGTTTA CACCTTCCGC GTAAACGCCC ACTGTACA TCCAAAACTC AGACACAAAA TAACCACCTC AAGAAGATAA ATAATGATAA GAAATAAATG TTACGCGAGG CAAATTTATT CACATGGGGC TTCCCAGGCC ACTTTGTGGT CAGCCGGGAG GGACGTTTTT GCCGTCCCAC GACTCCAACG GGCAGCCGGG CCTACGCAAA CATGGAAATC TTCCAAGAGC CTCCCTGGCC 50 CCCAGGGCTC AGAGGGTGGC AGAGCGGAGA GCGAAGGTGG CCGCAGCCTT CCCGGCCCCA CAGCCAGCCT GGCTCCAGCT GGGCAGGAGT GCAGAGCTCA GCTGGAGGCG AGGGGGAAGT GCCCAGGAGG CTGATGACAT CACTACCCAG CCCTTCAAAG ATGAGCTGTr CCCGCCGCCA CTCCAGCTCT GGCTTCTGGG CTCCGAGGAG GGGTGGGGAC GGTGGTGACG GTGGGGACAT CAGGCTGCCC CGCAGTACCA GGGAGCGACT GAAGTGCCCA TGCCGCTTGC TCCGGAGAAG GTGGGTGCCG GGCAGGGGCT GCTCCAGCCG CCTCACCTCT GCTGGGAGGA 55 CAAACTGTCC CAGCACAGAG GGAGGGAGGG AGGGCAGGCA GCGGGGAGAA GTTTCCCTGT GGTCGTGGGG AGTTGGGAAA AGTTCCCTTC CTTCCGGAGG GAGG CAGATTCACA AACTGCAGGA CTGGGCAGGG AGCAGACAGT GAGCAAACGC CAGCAGGGCT GCTGTGAATT TGTGTAAGGA TTGAGGGACA GTTGCTTTTC AGCATGGGCC CAGGAATGCC AAGGAGACAT CTATGCACGA CCTTGGGAAA TGAGTTGATG TCTCCGGTAA AACACCGGAG ACTAATTCCT GCCCTGCCCA ATTGCAGG GAGCATGGCT GTGAGGATGG GGTGAACTCA 60 CGCACAGCCA AGGACTCCAA AATCACAACA GCATTACTGT TCTTATTTGC TGCCACACCT GAGCCAGCCT GCTCCTTCCC AGGAGTGGAG GAGGCCTGGG GGGAGGGAGA GGAGTGACTG AGCTTCCCTC CCGTGTGTTC TCCGTCCCTG CCCCAGCAAG ACAACTTAGA TCTCCAGGAG AACTGCCATC CAGCTTTGGT GCAATGGCTG AGTGCACAAG TGAGTTGTTG CCCTGGGTTT CTTTAATCTA TTCAGCTAGA ACTTTGAAGG ACAATTTCTT GCATTAATAA AGGTTAAGCC CTGAGGGGTC CCTGATAACA ACCTGGAGAC CAGGATTA TGGCTCCCCT 65 CACTGATGGA CAAGGAGGTC TGTGCCAAAG AAGAATCCAA TAAGCACATA TTGAGCACTT GCTGTATATG CAGTATTGAG CACTGTAGGC AAGACCCAAG AAAGAGAAGG AGCCATCTCC ATCTTGAAGG AACTCAAAGA WO 00/62736 PCT/US00/08020 269 CTCAAGTGGG AACGACTGGG CACTGCCACC ACCAGAAAGC TGTTCGACGA GACGGTCGAG CAGGGTGCTG TGGGTGATAT GGACAGCAGA AGGGGGAGAC CAAGGTTCCA GCTCAACCAA TAACTATTGC ACAACCACCT GTCCCTGCCT CAGTTCCCTT TTATGTAACA TGAAGTCGTT GTGAGGGTTA AAGGCAGTAA CAGGTATAAA GTACTTAGAA AAGCAAAGGG TGCTACGTAC ATGTGAGGCA TCATTACGCA GACGTAACTG GGATATGTTT 5 ACTATAAGGA AAAGACACTG AGGTCTAGAA ATAGCTCCGT GGAGCAGAAT CAGTATTGGG AGCCGGTGGC GGTGTGAAGC ACCAGTGTCT GGCACACAGT AGGTGCTCAT TGGCTCCCTT CCACCTGTCA TTCCCACCAC CCTGAGGCCC CAACCGCCAC ACACACAGGA GCATTTGGAG AGAAGGCCAT GTCTTCAAAG TCTGATTTGT GATGAGGCAG AGGAAGATAT TTCTAATCGG TCTTGCCCAG AGGATCACAG TGCTGAGACC CCCCACCACC AGCCGGTACC TGGGAAGGGG GAGAGTGCAG GCCTGCTCAG GGACTGTTCC TGTCTCAGCA ACCAAGGGAT 10 TGTTCCTGTC AATCAATGGT TTATTGGAAG GTGGCCCAGT ATGAGCCCTA GAAGAGTGTG AAAAGGAATG GCAATGGTGT TCACCATCGG CAGTGCCAGG GCAGCACTCA TTCACTTGAT AAATGAATAT TTATTAGCTG GTTGGAGAGC TAGAACCTGG AGAGCTAGAA CCTGGAGAAC TAGAACCTGG AGGGCTAGAA CCTGGAGAGG CTAGAACCAA GAAGGGCTAG AACCTGGAGG GGCTAGAACC TAGAGAAGCT AAAACCTGAG CTAGAAGCTG GAGGACTAGA ACCTGGAGGG CTGGAATCTG AAGGGCTAGA ACCTGGAGGG CTGGAATCTG GAGAGCTAGA 15 ACCTGGAGGG CTAGAACCTG GAGGGCTAGA ACCTAGAAGG GCTAGAACCT GGAGGGCTGG AATCTGGAGA GCTAGAACCT GGAGGGCTAG AACCTGGAGG GCTAGAACCT AGAAGGGCTA GAACCTGGAG GGCTAGAACC TGGCAGGTTA GAACCTAGAA GGGCTAGAAC CTGGAGAGCC AGAACCTGGA GGGCTAGAAC CTGGAAGGGC TAGAACCTGT AGAGCTAGAA CATGGAGAGC TAGAACCCGG CAGGCTAGAA CCTGGCAAGC TAGAACCTGG AGGGAATGAA CCTGGAGGGC TAGAACCTGG AGAATGAGAA AAATTTACAT GGCAAAGAGC CCATAAATCC 20 TGACCAATCC AACTCTGAAT TTTAAAGCAA AAGCGTGAAA AAAAAGATTC CCTCCTrACC CCCAACCCAC TCTTTTTCC CACCACCCAC TCTCCTCTGC CTCAGTAAGT ATCTGGAGGA AGAAAACAGG TGAAAGAAGA AGTAAAAACC ATTTAGTATT AGTATTAGAA TGAAGTCAAA CTGTGCCACA CATGGTGAAT GAAAAAAAAA AAAAAGAGGC TGTGTTGT CACACAGGGC AGTCATTCAG CACCAGAGCA CGTGATGGTC TGAGACTCTC TTAGGAGCAG AGCTCTGCCG CAATGGCCAT GTGGGGATCC ACACCTGGTC TGAGGGGCAA CTGAGTCTGC 25 GGGAGAAGAG CGGCCCTATG CATGGTGTAG ATGCCCTGAT AAAGAACATC TGTCCTGTGA AAGACTCAAT GAGCTGTTAT GTTGTAAACA GGAAGCATTT CACATCCAAA CGAGAAAATC ATGTAAACAT GTGTCTTTTC TGTAGAGCAT AATAAATGGA TGAGGTTTTT GCAAAAAAAA AAAAAAAAA AAATGATAGA CCGTCAATAA TTTGTTAAAT GCTTTAAA ATGAATGCTT TAAGCCGGGT GCAGTGCCTC ACATCTGTAA TCCCAGCACT TTGGAGCCGA GCGGGTGGAT TGTGTGAGGT CAGGAGTTCG AGACCAACCT GGCCAACATG GCAAAACCTC 30 ACTCTCTACC AAAAATACAA AAATTAGCCA GGCATGGTGG CAGGCACCTG TGATCCCAGC TACTCAGGAG GCTGAGACAG GAGAATCGCT TGAACCCGGG AGGCAAGGTr GCAGTGAGCC AAGATTACGC CATTGTACTC CAGCCTGGGT GACAGAGAGA GACTCCGTCT CAAAAAAAAA AAAAAAAAAA AAAAAATTAC GCTTCAAACA CATGATCTCT CACCACTGTr GAATTTTCTr TCTATGAGCC CAGGAGGGCC TCTCAGAGAG GAAAGCTCCT AGGTCTTCCT TrCCCTCTGC AAACTCCCTG CCTTGAAGGT TCAGAAGGAC TGTGCGTGCT CGTTGCATCC 35 TTTGCAAGTG TCCAAACCCT GATCCCAGCT GTGCTTAGGG GTTCCTGCAA ACCTTTrCCA GGTGTTAATT ACCTCCCACT TCAYTCCTG TTTACCAACT CAGCTTG TTAGTGTG TGAATTCC CTGAACTGAC CGTTGTCTGA TCTCCACCTC CCAACTGAAT TAGGGGAGCT GGGCTTCTGG AAACCCAGGT GCCGGGTGTT GCAGAGTGGC TGAAAGCTGG GATGTGGCAG ATCCGTGGCT ACATTCATGC ACACACACAC ACCCACATAC CCACACATGC ACACACACAC ACACACCCGC ACTCACACAC TTGGACATGC ATAGACCACA GCTTTCCACA 40 CCCTTCCTAG ACAGGGGTCA CTTGGTATCC TGGAGAGAGT GTGAAGTCCT GGAATGGAAA GAGGGGGGAT TAAGCCCCAC CTCTAGCCAT GGGACTGAGA CAAGTCACCA CCAACCCATC TGCGCCTTGT TFACCTCCTC TGTGAGGCAA GCACAGAGCC CATGCCTGCC CCCCTGGATG GGAGTGATGT GAAACTrGAA GGGCGGTCAG AGCAAGGGTC GGGAATGGAA GGCCCTTGGG AAAAAAGGCC CTTTCAACTA GGGGCACAGA GGAGGCCCTG GGCTGAGAAC TTGACAGCAC CTTGTAATTG GTAAGCCAAG CCCGAAGGGA CTGGAAATAC TCAGATGTGT 45 CTGTCTCCCT TATTAGGTTC AAAGTCCCTC AAGACCCTGT CTCCATCACA GTGCTCCAGT CCAGACCCCT CCTCTGAGCT CCAGACCCTG CTGGACCCAA CCAGCCCTAT GGGGTCGCAT CCCCACCTGC CTGGAATTCT CCAAAGAACC TCCCCTTTAA CAG17CCAGC CTTAACAGT TCCAGTCTAA ACACATGACC TTITCTCCTCT AAATCAGCCC CCCATCTCTG CCTGCAGG AGATGGAAGC CATGACACCT GCCTCGCCCC TGTCCTCACC CCATCCATGT CCAATCAAGC ACTAGGCATG TCAGGTTTAC CCTCTAAACT CCTCTGGAAT CCAGTCTCTC 50 AGTCTCCATC ATCCCAGGTC GAAGCTAATG GGCTAACTGG TCCTTGCTTC CACTCTACCC CCACTGCAGT CCTGACTTCC TGAGCAGCAG CCAGGGCCTA ATCGATATTC ACACCAAGCG CCAACCTGAC TGAGATATCC TCCTGCACCA TCATCCCTCC ACCCTGTTTA GTTCTGCTCA CCCTCAGTGT TCTCATCAAT AATCCACTCC CCTCACAGGC GCGTTGGGA CCCCATGTTC TATGCTCTCA CAGGACC TT TGCTTGATTT TTCACTGTAC TTAGGTCAGT TTGCAGTTAT TAAGTGACTG AGCAATGTCT GGCTTCTCCA GTAGACTGTC AGCTCCTAGC 55 CATTGTATAC CTAGCACCGC TGTGTGGGAG CACGTGACAA ACGTCCAGTG AGTCAGGGAC TCAGCAGTCT CCATTTCTCC GCCCTGCTGG AGAATGCGTG TATTTGGCAA TCCCCAGCCC CTGTGCCATC TAACCATCTT TTCTTCTCTG TTCAGCCCAG GTGTGGCCTC ACTCACATCC CACTCTGAGT CCAAATGTTC TCTCCCTGGA AGATATCAAT GTTTCTGTCT GTTCGTGAGG ACTCCGTGCC CACCACGGCC TCTTTCAGGT GAGTCAAAGG GATTCCTCAG TTCACTAGTT AGGGGAGGTG GGCAGACACC CTGGAGAACT CCCTGGAAAG CTCAACTCTC 60 ATGCCCCGGA CAACAGTrGA AGGAACCATG GTGATGTTAA GCCCAAAGAC AAAACCTCTC AGGTGTCCAA GTCCCTGTTG GAATCTTGGG AGCAGAGGGA ATGTTCTGTG GTCTAGAGGA AGAGGGGCTC AGGGAGGAGA AGGGCACATT CCTGGTTGTT ATATGTTTCT ATCTATCCCA GATGAACTTG GAAGTGAAGG GAAGAGAGTT AAACATTAAA GTAAATACCC AGTGGATCAG ACAGCAATGT GCCAGATTGC CTTGGAAACA AAATATCTCC AACACATGGC TGACATTTGG TGGGAGATCA GAACACCCTA AAGAGAGAAT TTAAGGGGAG GGGGAGGAGG 65 ACCTGAGCCA GAGTAGAAGC AGAGGATAGG GAGATCTGTT CTTGGGGACA GCATTTGCAA GAAACAAGGC TGAGGGGTCC ACTCCAACCT CTCCACCCTG CTGCAGGTGC TGCCTATGAT GAAGATGAGC AGATGGCCAT WO 00/62736 PCT/USOO/08020 270 CTCAGCTGGG GCCACAGTGC ACTGGACCTA TAGTTTCCAA TTCCGCACTC AGCAGGCATC TICTGATGA TCCGATGGCT TCTCAGAGCC AGGGATGGGC CAGGATCCAT CCCCTTGGCT ACTGTCTTGC TGAGAAATI1T ATAAGCAGCA TCTGGTGCTA TACTTrGGTC TCTAGTGAGT TAGCTCATGA AAGATGATAG ACTCTCCAAG CCAGGGGTAT GCAGGAAATG GG'IPCTGT AGCTACAGAA ATGGGGTI7GA GGG H'GGACC AAGGGACTAC 5 CCAGGGGAAG TCTrACC'rrC AGAGGACTCT GGAAAGGAGG CTGCAAGMT TCATGGGTCA AGAATTCAGA GCCCAGTAGA GACAGCTTAT CTCTGTI'GCA AGATGTCTGG GGCC'FrGGTT GGAAGAUTCA AAGGCTAGGA AACCAGGAGC CACCAAAAGC GTAACTGGGG CCAGAGGATC CAC'TrCAAG GTGGCAAGYP GGTTCCCCCC ATGTGGCTGC TTGAGTATCC TCACATGGCG GCTCACATCC Tr1CCAAGTAA GCAATGCAAA AGGCCAAGAA AGATGCTGCA AAGATGTTAT GACCTAGCCT CAGAAATCAC ACACCATCCC TGCCACCATT AGTAAGAAGT 10 CCAGCCCACG TCCAGGAGAA GAGGAAGCAG ATrccTccT-r TI1GAAATGAA GAATATCAAG TAATTCGGGG GGCATATGAA AGCCACCACA CACCACAGGG ATC1r=AG AGCATAITrC TTATACCATC ACTGTAGTFC CTrAAGACTC AGGGGCAAAG CCTCACTTCC TTAGCACCCA GTGAAGACCA CGCTTACTCC CTCACTCAAC CTCTTrGCTAC TTCCCACCTC TCCTGTCCAA CATCTAGTGT CACTITCCAG AACATACCAA CAGCTTCCCC AGTTCTGTGC CTCTGCTCAG GCTGTFCCCC CTGCCTGGTC CACTGTCCT C=TCTTGTC CGGTCAAAAT 15 GCTTCTrATC CTrrCAAGACC CAGCTCTAGA GTCACCTCCA ACCCCT7ACC CACCAGCCCC CTCTCCAAGT CTGTGTCCCA CAACCCCCCT GCTCCCTCCA GGGCACCCTC CACCCTCTGG GCCACAGTTG TCAGGAGTCA GGCAGGGCAG GGGCCGGGTG GTGTCTCr TGTGTTCTrG CACTCAGGGC AGAGCTCAGC ACAGAGCAGA CGCTCAAAAA ACA ITTAAAG GATAGAAGCA TTGATTTGTG GGTCCCCCAG TCTGGCTCCA GGATGCCAGC CAGCTGCTCC TAGAAGCAAA CGGACT M C CTGGGAAATC CCAGAGGTGA TGATCAGTAA TCTCTCCCGT 20 GACTCGTAGT TCAGCTCTTC CTCCATGAGC CTGACTATCA GTGGACC'TC CAGAAAGAGC CCCTrCCT TCTCTCACCC ACAGCACAGG GCACTGGGAA AATGCCCAAT GAGTCCTGCC TCTGGGITGT GCTTGGACT FICAGTGTG TCTCGCATCC ACTC'ICAAC TTGAATGT7G CAACAGCCAT GAAAAAAGAA ATGCAAAGCG ATT1CAGGATG AGAGCAATAC CCTACTCCAA AGAAGGCAAC ATAGAAGCTC AGAGAGATCA AGCAATI"GC CCAAGACCAC ACAGCTAGGA GTGGAACTCA TGGCTGTCCA AGCCCCATGC CTCTGCTGAA GGTAGAGATG 25 AA'ITACAGCA ACAAGTCTAG AAAGGTGCCT GCCCTATGGT CTGTGAGTCT TGCCTAAGAA TGAAAGAGGA GCCAGTGGGT TAAAGATGAG GTCACCAACA ACGGTGGTGT TGGAG'ITAC CACTGATAAT AAGGGTGCAA AATGTAAATT ACTAATGT ATTGAGCCTA GTGCAGTGCG TGGGGCATIT TGCACATTGT CTCTGATCCC TATGACAACC CTGAGAGGTA GTGGT=TAA CTGCCATG'IT ACAGGTGAGG TCATTGTGGT TCAAGGACGT TAAGTAACTT CCCCAGCGTG ACACGGCTTA TAAGTAAGGC AGCCAGGATG TGAACCCAGT AGGACTATCT 30 GGCTGCAAAG TCCCCACCCC CCTCGCCATC TGTATCCTCC AATCACTT1CA GTGCTrTGCT GCATAGAAGG TAACGGAAAT CACGATGCCA CAGACTGTCC AGGAAGACAG AAACTAGGCA GATGGGCTGG CCATGGTCTC CAAGCCAGAC TGGAATCTCC AGGTCTGGAA TGATATCA'IT TITCTC'ITI AATAAATTAA CTCACCCACC ACACGGC'ITT GAGAGGCTCA AAG'ITGACCA ACTCCCTTGG GAGGGCCCCG GYTGATAAGG AAGGAACGTG AATCCTCCCA TCACGGAAGC TTCAAGGAGG TCAAGGGTCC AACACTrGAG ATFGTTAGTG CTGTTGGTGG 35 ATACTGGCCA AGGAAATATC CCAGTGGAGC CTCGAGATGA AGAACATGAG GCCCCCG IT AGAACCAAGG ATCAGAGGGG GCTCTGTAAG ACCCAGGGGA GTCAGGTGCA CTGGAGCGCG GGCATGCAGA AAACAGCCTG AGCTCCACCT CG.GCTI1CTCC TTGTCCTGGC TGGT7GTCCT TAACCCCTGT CTCCTTCTGG ACCAG'rrITr GTCCTrCCCT TGTGACCGCT GAGGGGTAAC AGCCTCITC CA=CT1T CAGCGCCGAC ATGCTCAATG TCACCTTGCA AGGGCCCACT CTTAACGGGA CCTTTGCCCA GAGCAAATGC CCCCAAGTGG AGTGGCTGGG 40 CTGGCTCAAC ACCATCCAGC CCCCCTTCCT CTGGGTGCTG TI1CGTGCTGG CCACCCTAGA GAACATCTrT GTCCTCAGCG TCTrCTGCCT GCACAAGAGC AGCTGCACGG TGGCAGAGAT CTACCTGGGG AACCTGGCCG CAGCAGACCT GATCCTGGCC TGCGGGCTGC CC=TCTGGGC CATCACCATC TCCAACAACT TCGACTGGCT C'rTGGGGAG ACGCTCTGCC GCGTGGTGAA TGCCA'ITATC TCCATGAACC TGTACAGCAG CATCTG=IC CTGATGCTGG TGAGCATCGA CCGCTACCTG GCCCTGGTGA AAACCATGTC CATGGGCCGG ATGCGCGGCG 45 TGCGCTGGGC CAAGCTCTAC AGCTrGGTGA TCTGGGGGTG TACGCTGCTC CTGAGCTCAC CCATGCTGGT GTTCCGGACC ATGAAGGAGT ACAGCGATGA GGGCCACAAC GTCACCGCTT GTGTCATCAG CTACCCATCC CTCATCTGGG AAGTGTTCAC CAACATGCTC CTGAATGTCG TGGGCT-rCCT GCTGCCCCTG AGTGTCATCA CCTTCTGCAC GATGCAGATC ATGCAGGTGC TGCGGAACAA CGAGATGCAG AAGTTCAAGG AGATCCAGAC GGAGAGGAGG GCCACGGTGC TAGTCCTGGT TGTGCTGCTG CTATTCATCA TCTGCTGGCT GCCCTTCCAG 50 ATCAGCACCT TCCTGGATAC GCTGCATCGC CTCGGCATCC TCTCCAGCTG CCAGGACGAG CGCATCATCG ATGTAATCAC ACAGATCGCC TCCTTCATGG CCTACAGCAA CAGCTGCCTC AACCCACTGG TGTACGTGAT CGTGGGCAAG CGCTTCCGAA AGAAGTCTTG GGAGGTGTAC CAGGGAGTGT GCCAGAAAGG GGGCTGCAGG TCAGAACCCA TTCAGATGGA GAACTCCATG GGCACACTGC GGACCTCCAT CTCCGTGGAA CGCCAGATTC ACAAACTGCA GGACTGGGCA GGGAGCAGAC AGTGAGCAAA CGCCAGCAGG GCTGCTGTGA AITTGTGTAA 55 GGATTGAGGG ACAG'FrGCTT TTCAGCATGG GCCCAGGAAT GCCAAGGAGA CATCTATGCA CGACCTTFGGG AAATGAGT'TG ATGTCTCCGG TAAAACACCG GAGACTAATT CCTGCCCTGC CCAATrTrGC AGGGAGCATG GCTGTGAGGA TGGGGTGAAC TCACGCACAG CCAAGGACTC CAAAATCACA ACAGCATI'AC TGTTCTTA'rr TGCTGCCACA CCTGAGCCAG CCTGCTCCTT CCCAGGAGTG GAGGAGGCCT GGGGGCAGG3G AGAGGAGTGA CTGAGCTTCC CTCCCGTGTG TTCTCCGTCC CTGCCCCAGC AAGACAACTT AGATCTCCAG GAGAACTGCC 60 ATCCAGC'TI7 GGTGCAATGG CTGAGTGCAC AAGTGAG'ITG TTGCCCTGGG 'IMCIFAAT CTATTCAGCT AGAACTTTGA AGGACAATTr CTGCATTAA TAAAGGTTAA GCCCTGAGGG GTCCCTGATA ACAACCTGGA GACCAGGATT TTATGGCTCC CCTCACTGAT GGACAAGGAG GTCTGTGCCA AAGAAGAATC CAATAAGCAC ATATTGAGCA CITGCTGTAT ATGCAGTATI' GAGCACTGTA GGCAAGAGGG AAGAAAGAGA AGGAGCCATC TCCATCTTGA AGGAACTCAA AGACTCAAGT GGGAACGACT GGGCACTGCC ACCACCAGAA AGCTGTTCGA 65 TGAGACGGTC GAGCAGGGTG CTGTGGGTGA TATGGACAGC AGAAGGGGGA GCCAGGTTCC AGCTCACCAA TACTATTGCA CACCACCTGT CCTGCCTC CTGCAGAAAA CAGCCTGAGC TCCACCTCGG CT7CTCCTTG WO 00/62736 PCT/USOO/08020 271 CCCTGGCTGG TTGTCCTTAA CCCCTGTCTC CTTCTGGACC AGTITGTC CTTCCCTTGT GACCCTGAGG GGTAACAGCC TC'TTCCAC TTTCITCAG CGCCGACATG CTCAATGTCA CCTTGCAAGG GCCCACTCTT AACGGGACCT TTGCCCAGAG CAAATGCCCC CAAGTGGAGT GGCTGGGCTG GCTCAACACC ATCCAGCCCC CCTTCCTCTG GGTGCTGTTC GTGCTGGCCA CCCTAGAGAA CATCTTTGTC CTCAGCGTCT TCTGCCTGCA 5 CAAGAGCAGC TGCACGGTGG CAGAGATCTA CCTGGGGAAC CTGGCCGCAG CAGACCTGAT CCTGGCCTGC GGGCTGCCCT TCTGGGCCAT CACCATCTCC AACAACTTCG ACTGGCTCITT TGGGGAGACG CTCTGCCGCG TGGTGAATGC CATTATCTCC ATGAACCTGT ACAGCAGCAT CTGTTTCCTG ATGCTGGTGA GCATCGACCG CTACCTGGCC CTGGTGAAAA CCATGTCCAT GGGCCGGATG CGCGGCGTGC GCTGGGCCAA GCTCTACAGC TFGGTGATCT GGGGGTGTAC GCTGCTCCTG AGCTCACCCA TGCTGGTGTT CCGGACCATG AAGGAGTACA 10 GCGATGAGGG CCACAACGTC ACCGCTTGTG TCATCAGCTA CCCATCCCTC ATCTGGGAAG TGTTCACCAA CATGCTCCTG AATGTCGTGG GCTTCCTGCT GCCCCTGAGT GTCATCACCT TCTGCACGAT GCAGATCATG CAGGTGCTGC GGAACAACGA GATGCAGAAG TTCAAGGAGA TCCAGACGGA GAGGAGGGCC ACGGTGCTAG TCCTGGTTGT GCTGCTGCTA TTCATCATCT GCTGGCTGCC CTTCCAGATC AGCACCTTCC TGGATACGCT GCATCGCCTC GGCATCCTCT CCAGCTGCCA GGACGAGCGC ATCATCGATG TAATCACACA GATCGCCTCC 15 TTCATGGCCT ACAGCAACAG CTGCCTCAAC CCACTGGTGT ACGTGATCGT GGGCAAGCGC TTCCGAAAGA AGTCTTGGGA GGTGTACCAG GGAGTGTGCC AGAAAGGGGG CTGCAGGTCA GAACCCATTC AGATGGAGAA CTCCATGGGC ACACTGCGGA CCTCCATCTC CGTGGAACGC CAGATTCACA AACTGCAGGA CTGGGCAGGG AGCAGACAGT GAGCAAACGC CAGCAGGGCT GCTGTGAATT TGTGTAAGGA TTGAGGGACA GTTGCTTTTC AGCATGGGCC CAGGAATGCC AAGGAGACAT CTATGCACGA CCTTGGGAAA TGAGTTGATG TCTCCGGTAA 20 AACACCGGAG ACTAATTCCT GNCCTGCCCA ATTGCAGG GAGCATGGCT GTGAGGATGG GGTGAACTCA CGCACAGCCA AGGACTCCAA AATCACAACA GCATTACTGT TCTTATTTGC TGCCACACCT GAGCCAGCCT GCTCCTTCCC AGGAGTGGAG GAGGCCTGGG GGCAGGGAGA GGAGTGACTG AGCTTCCCTC CCGTGTGTTC TCCGTCCCTG CCCCAGCAAG ACAACTTAGA TCTCCAGGAG AACTGCCATC CAGCTTTGGT GCAATGGCTG AGTGCACAAG TGAGTTGTTG CCCTGGGTTT CTTTAATCTA TTCAGCTAGA ACTTTGAAGG ACAATTTCTT 25 GCATTAATAA AGGTTAAGCC CTGAGGGGTC CCTGATAACA ACCTGGAGAC CAGGATTA TGGCTCCCCT CACTGATGGA CAAGGGAGGT CTGTGCCAAA GAAGAATCCA ATAAGCACAT ATTGAGCACT TGCTGTATAT GCAGTATTGA GCACTGTAGG CAAGAGGGAA GAAAGAGAAG GAGCCATCTC CATCTTGAAG GAACTCAAAG ACTCAAGTGG GAACGACTGG CACTGCCACC ACCAGAAAGC TGTTCGACGA GACGGTCGAG CAGGGTGCTG TGGGTGATAT GGACAGCAGA AGGGGGAGAC CAAGGTTCCA GCTCAACCAA TAACTATTGC ACAACCACCT 30 GTCCCTGCCT CAGTTCCCTC TTCTGTAACA TGAAGTCGTTr GTGAGGGTTA AAGGCAGTAA CAGGTATAAA GTACTTAGAA AAGCAAAGGG TGCTACGTAC ATGTGAGGCA TCATTACGCA GACGTAACTG GGATATGT ACTATAAGGA AAAGACACTG AGGTCTAGA TGATCCTATC ACAACCTGAG AGTAGTT ACTCCATTTA CAGGTGAGGT CATrGTGGTT CAAGGACGTT AAGTAACTTC CCCAGCTCAC ACGGCTTATA AGTAAGGCAG CCAGGATGTG AACCCAGTAG GACTATCTGG CTGCAAAGTC CCCACCCTCC CTCGCCATCT GTATCCTCCA 35 ATCATCTTCA GTGCTTGCT GATAGAAGGT ACGGAAATAC GATGCCACAG ACTGTCCAGG AAGACAGAAA CTAGGCAGAT GGGCTGGCCA TGGTCTCCAA GCCAGACTGG AATCTCCAGG TCTGGAATGA TATCATTT CTCTTTTAAT AAATTAACTC ACCCACCACA CGGCTTTGAG AGGCTCAAAG GTGACCAACT CCCTTGGGAG GGCCCCGGTT GATAAGGAAG GAATGTGAAT CCTCCCATCA CGGAAGCTTC AAGGAGGTCA AGGGTCCAAC ACTTGAGATT GTTAGTGCTG TTGGTGGATA CTGCAGAATA TCCAGTGGAG CCTCAGATGA AGAACATGAG 40 GCCCCGTTTA GATCCAAGGA TCAGAGGGGG CTCTGTAAGA CCCAGGGGAG TCAGGTGCAC TGGAGCGCGG GCTGCAGAAA ACAGCCTGAG CTCCACCTCG GC'TTCTCCTT GCCCTGGCTG GTTGTCCTTA ACCCCTGTCT CCTTCTGGAC CAGTrTGT CCTTCCCTTG TGACCTGAGG GGTAACAGCC TCTTTTCCAC TTTCTTTCAG CGCCGACATG CTCAATGTCA CCTTGCAAGG GCCCACTCTT AACGGGACCT TTGCCCAGAG CAAATGCCCC CAAGTGGAGT GGCTGGGCTG GCTCAACACC ATCCAGCCCC CCTTCCTCTG GGTGCTGTTC GTGCTGGCCA 45 CCCTAGAGAA CATCTTTGTC CTCAGCGTCT TCTGCCTGCA CAAGAGCAGC TGCACGGTGG CAGAGATCTA CCTGGGGAAC CTGGCCGCAG CAGACCTGAT CCTGGCCTGC GGGCTGCCCT TCTGGGCCAT CACCATCTCC AACAACTTCG ACTGGCTCTT TGGGGAGACG CTCTGCCGCG TGGTGAATGC CATTATCTCC ATGAACCTGT ACAGCAGCAT CTGTTCCTG ATGCTGGTGA GCATCGACCG CTACCTGGCC CTGGTGAAAA CCATGTCCAT GGGCCGGATG CGCGGCGTGC GCTGGGCCAA GCTCTACAGC TTGGTGATCT GGGGGTGTAC GCTGCTCCTG 50 AGCTCACCCA TGCTGGTGTT CCGGACCATG AAGGAGTACA GCGATGAGGG CCACAACGTC ACCGCTTGTG TCATCAGCTA CCCATCCCTC ATCTGGGAAG TGTTCACCAA CATGCTCCTG AATGTCGTGG GCTTCCTGCT GCCCCTGAGT GTCATCACCT TCTGCACGAT GCAGATCATG CAGGTGCTGC GGAACAACGA GATGCAGAAG TTCAAGGAGA TCCAGACGGA GAGGAGGGCC ACGGTGCTAG TCCTGGTTGT GCTGCTGCTA TTCATCATCT GCTGGCTGCC CTTCCAGATC AGCACCTTCC TGGATACGCT GCATCGCCTC GGCATCCTCT CCAGCTGCCA 55 GGACGAGCGC ATCATCGATG TAATCACACA GATCGCCTCC TTCATGGCCT ACAGCAACAG CTGCCTCAAC CCACTGGTGT ACGTGATCGT GGGCAAGCGC TTCCGAAAGA AGTCTTGGGA GGTGTACCAG GGAGTGTGCC AGAAAGGGGG CTGCAGGTCA GAACCCATTC AGATGGAGAA CTCCATGGGC ACACTGCGGA CCTCCATCTC CGTGGAACGC CAGATTCACA AACTGCAGGA CTGGGCAGGG AGCAGACAGT GAGCAAACGC CAGCAGGGCT GCTGTGAATT TGTGTAAGGA TTGAGGGACA GTTGCTTC AGCATGGGCC CAGGAATGCC AAGGAGACAT 60 CTATGCACGA CCTTGGGAAA TGAGTGTTGA TGTCTCCGGT AAAACACCGG AGACTAATTC CTGCCCTGCC CAATTTTCGA GGGAGCATGG CTGTGAGGAT GGGGTGAACT CACGCACAGC CAAGGACTCC AAAATCACAA CAGCATTACT GTTCTTATTT GCTGCCACAC CTGAGCCAGC CTGCTCCTTC CCAGGAGTGG AGGAGGCCTG GGGGAGGGAG AGGAGTGACT GAGCTTCCCT CCCGTGTGTT CTCCGTCCCT GCCCCAGCAA GACAACTTAG ATCTCCAGGA GAACTGCCAT CCACGTTGG TGCAATGGCT GAGTGCACAA GTGAGTTGTT GCCCTGGGTT 65 TCTTTAATCT ATCAGCTAGA ACTTTGAAGG ACAATITCTT GCATTAATAA AGGTTAAGCC CTGAGGGGTC CCTTGATAAC AACCTGGAGA CCAGGATTr ATGGCTCCCC TCACTGATGG ACAAGGAGGT CTGTGCCAAA WO 00/62736 PCT/USOO/08020 272 GAAGAATCAA TAAGCACATA TGAGCACTTC TGTATATCAG TATTGAGCAC TGTAGGCA ATGTTCTCTC CCTGGAAGAT ATCAATGTTr CTGTCTGTTT GTGAGGACTC CGTGCCCACC ACGGCCTCTT TCAGCGCCGA CATGCTCAAT GTCACCTTGC AAGGGCCCAC TCTTAACGGG ACCTTTGCCC AGAGCAAATG CCCCCAAGTG GAGTGGCTGG GCTGGCTCAA CACCATCCAG CCCCCCTrCC TCTGGGTGCT GTTCGTGCTG GCCACCCTAG 5 AGAACATCTT TGTCCTCAGC GTCTTCTGCC TGCACAAGAG CAGCTGCACG GTGGCAGAGA TCTACCTGGG GAACCTGGCC GCAGCAGACC TGATCCTGGC CTGCGGGCTG CCCTTCTGGG CCATCACCAT CTCCAACAAC TTCGACTGGC TCTTTGGGGA GACGCTCTGC CGCGTGGTGA ATGCCATTAT CTCCATGAAC CTGTACAGCA GCATCTGTTT CCTGATGCTG GTGAGCATCG ACCGCTACCT GGCCCTGGTG AAAACCATGT CCATGGGCCG GATGCGCGGC GTGCGCTGGG CCAAGCTCTA CAGCTTGGTG ATCTGGGGGT GTACGCTGCT CCTGAGCTCA 10 CCCATGCTGG TGTTCCGGAC CATGAAGGAG TACAGCGATG AGGGCCACAA CGTCACCGCT TGTGTCATCA GCTACCCATC CCTCATCTGG GAAGTGTTCA CCAACATGCT CCTGAATGTC GTGGGCTTCC TGCTGCCCCT GAGTGTCATC ACCTTCTGCA CGATGCAGAT CATGCAGGTG CTGCGGAACA ACGAGATGCA GAAGTTCAAG GAGATCCAGA CGGAGAGGAG GGCCACGGTG CTAGTCCTGG TTGTGCTGCT GCTATTCATC ATCTGCTGGC TGCCCTTCCA GATCAGCACC TTCCTGGATA CGCTGCATCG CCTCGGCATC CTCTCCAGCT GCCAGGACGA 15 GCGCATCATC GATGTAATCA CACAGATCGC CTCCTTCATG GCCTACAGCA ACAGCTGCCT CAACCCACTG GTGTACGTGA TCGTGGGCAA GCGCTTCCGA AAGAAGTCTT GGGAGGTGTA CCAGGGAGTG TGCCAGAAAG GGGGCTGCAG GTCAGAACCC ATTCAGATGG AGAACTCCAT GGGCACACTG CGGACCTCCA TCTCCGTGGA ACGCCAGATT CACAAACTGC AGGACTGGGC AGGGAGCAGA CAGTGAGCAA ACGCCAGCAG GGCTGCTGTG AATTTGTGTA AGGATTGAGG GACAGTTGCT T ATGTTCTCTC CCTGGAAGAT ATCAATGTTT CTGTCTGTTC 20 GTGAGGACTC CGTGCCCACC ACGGCCTCTT TCAGCGCCGA CATGCTCAAT GTCACCTTGC AAGGGCCCAC TCTTAACGGG ACCTTTGCCC AGAGCAAATG CCCCCAAGTG GAGTGGCTGG GCTGGCTCAA CACCATCCAG CCCCCCTTCC TCTGGGTGCT GTTCGTGCTG GCCACCCTAG AGAACATCTT TGTCCTCAGC GTCTTCTGCC TGCACAAGAG CAGCTGCACG GTGGCAGAGA TCTACCTGGG GAACCTGGCC GCAGCAGACC TGATCCTGGC CTGCGGGCTG CCCTTCTGGG CCATCACCAT CTCCAACAAC TTCGACTGGC TCTTTGGGGA GACGCTCTGC 25 CGCGTGGTGA ATGCCATTAT CTCCATGAAC CTGTACAGCA GCATCTGTTT CCTGATGCTG GTGAGCATCG ACCGCTACCT GGCCCTGGTG AAAACCATGT CCATGGGCCG GATGCGCGGC GTGCGCTGGG CCAAGCTCTA CAGCTTGGTG ATCTGGGGGT GTACGCTGCT CCTGAGCTCA CCCATGCTGG TGTTCCGGAC CATGAAGGAG TACAGCGATG AGGGCCACAA CGTCACCGCT TGTGTCATCA GCTACCCATC CCTCATCTGG GAAGTGTTCA CCAACATGCT CCTGAATGTC GTGGGCTTCC TGCTGCCCCT GAGTGTCATC ACCTrCTGCA CGATGCAGAT 30 CATGCAGGTG CTGCGGAACA ACGAGATGCA GAAGTTCAAG GAGATCCAGA CGGAGAGGAG GGCCACGGTG CTAGTCCTGG YGTGCTGCT GCTATrCATC ATCTGCTGGC TGCCCTTCCA GATCAGCACC TTCCTGGATA CGCTGCATCG CCTCGGCATC CTCTCCAGCT GCCAGGACGA GCGCATCATC GATGTAATCA CACAGATCGC CTCCTTCATG GCCTACAGCA ACAGCTGCCT CAACCCACTG GTGTACGTGA TCGTGGGCAA GCGCTTCCGA AAGAAGTCTT GGGAGGTGTA CCAGGGAGTG TGCCAGAAAG GGGGCTGCAG GTCAGAACCC ATTCAGATGG 35 AGAACTCCAT GGGCACACTG CGGACCTCCA TCTCCGTGGA ACGCCAGATT CACAAACTGC AGGACTGGGC AGGGAGCAGA CAGTGAGCAA ACGCCAGCAG GGCTGCTGTG AATTGTGTA AGGATTGAGG GACAGTTGCT T GCCCTTCAAA GATGAGCTGT TCCCGCCGCC ACTCCAGCTC TGGCTTCTGG GCTCCGAGGA GGGGTGGGGA CGGTGGGGAC ATCAGGCTGC CCCGCAGTAC CAGGGAGCGA CTGAAGTGCC CATGCCGCTT GCTCCGGAGA AGGTGGGTGC CGGGCAGGGG CTGCTCCAGC CGCCTCACCT CTGCTGGGAG GACAAACTGT CCCAGCACAG 40 AGGGAGGGAG GGAGGGCAGG CAGCGGGGAG AAGTTTCCCT GTGGTCGTGG GGAGTT GCCCTTCAAA GATGAGCTGT TCCCGCCGCC ACTCCAGCTC TGGCTTCTGG GCTCCGAGGA GGGGTGGGGA CGGTGGTGAC GGTGGGGACA TCAGGCTGCC CCGCAGTACC AGGGAGCGAC TGAAGTGCCC ATGCCGCTTG CTCCGGAGAA GGTGGGTGCC GGGCAGGGGC TGCTCCAGCC GCCTCACCTC TGCTGGGAGG ACAAACTGTC CCAGCACAGA GGGAGGGAGG GAGGGCAGGC AGCGGGGAGA AGTTTCCCTG TGGTCGTGGG GAGTT GAGCTCTTCA 45 ATATTAGT GAAAGCTATA GATGAGGCTC CATAGGGGAT AAAGCACAGA CACACCTTT CAGAGGGCTT GTGGACTCTG GGCAGCCTGT CCATAGACCT CTGTCCCCAA CTGGCAAGTC AGGAAACTCC AGATTAAGGA GCCCCAATGT GGTTGAACAG CCAGGTGCAC AGATGAGTCA ACCACACAGC CAGGCCAGGG AGGGCCTTCA CTCAAGAGCC TACAGCCAGT TCACAGCCAA GCCAGGGCTA GCGCCAGGCC ACCCATAAAC TGATCTGAGA CTCTGTTTCC CTGTCTCCAT GATGATGGGA TCAGGCTTGA TTGCTGGTTT GTAGGCTTGT TATGAATCAA 50 GTCACAGGGA AGAGGAGCTG ATGGGCTGGG GGGACGTCCT CTGGCCCTCC TGTCTCTTCC CCAGATCCAC TGGGCCCACT CTTATCTGTT CTCTrCTGAA GGAAGGGTTT TAAGGCTTCA AAAAAAAATG TTTTGAAAGT CCCTGCCCTT TCCAGCTCCT ACCGTCTCAG CCCTGGGAGT GTAAAGTGCT GCAGATAGTT AGTAAGTCTT TGAGCAAAAC TGAGAAAGCC AGCCTGAGCC TTGACATGGG AGAAACCTCC GCCATACATC TCCGAAGAAA CGGCCGCGTG TCTCAGGGGA GCGCAAACAC CCGTACCCAG GAAACAGGAC AGCTTCTGCC ACTGTCGCCC 55 TTGGGAGCCG TACGTGGCAT GACAAAGAAA TCCCAGGACT CCGCCTGCCC ACCTGGCCAC CCTCTGTTTA CACCTTCCGC GTAAACGCCC ACTGTTTACA TCCAAAACTC AGACACAAAA TAACCACCTC AAGAAGATAA ATAATGATAA GAAATAAATG TTrACGCGAGG CAAATTTATT CACATGGGGC TTCCCAGGCC ACTTTGTGGT CAGCCGGGAG GGACGTTTTT GCCGTCCCAC GACTCCAACG GGCAGCCGGG CCTACGCAAA CATGGAAATC TTCCAAGAGC CTCCCTGGCC CCCAGGGCTC AGAGGGTGGC AGAGCGGAGA GCGAAGGTGG CCGCAGCCTT 60 CCCGGCCCCA CAGCCAGCCT GGCTCCAGCT GGGCAGGAGT GCAGAGCTCA GCTGGAGGCG AGGGGGAAGT GCCCAGGAGG CTGATGACAT CACTACCCAG CCCTTCAAAG ATGAGCTGTT CCCGCCGCCA CTCCAGCTCT GGCTTCTGGG CTCCGAGGAG GGGTGGGGAC GGTGGTGACG GTGGGGACAT CAGGCTGCCC CGCAGTACCA GGGAGCGACT GAAGTGCCCA TGCCGCTTGC TCCGGAGAAG GTGGGTGCCG GGCAGGGGCT GCTCCAGCCG CCTCACCTCT GCTGGGAGGA CAAACTGTCC CAGCACAGAG GGAGGGAGGG AGGGCAGGCA GCGGGGAGAA 65 GTTrCCCTGT GGTCGTGGGG AGTTGGGAAA AGTTCCCTTC CTTCCGGAGG GAGG CAGATTCACA AACTGCAGGA CTGGGCAGGG AGCAGACAGT GAGCAAACGC CAGCAGGGCT GCTGTGAATT TGTGTAAGGA WO 00/62736 PCT/USOO/08020 273 TTGAGGGACA GTTGCTTTTC AGCATGGGCC CAGGAATGCC AAGGAGACAT CTATGCACGA CCTrGGGAAA TGAGTTGATG TCTCCGGTAA AACACCGGAG ACTAATTCCT GCCCTGCCCA ATTTTGCAGG GAGCATGGCT GTGAGGATGG GGTGAACTCA CGCACAGCCA AGGACTCCAA AATCACAACA GCATTACTGT TCTTATTTGC TGCCACACCT GAGCCAGCCT GCTCCTTCCC AGGAGTGGAG GAGGCCTGGG GGGAGGGAGA GGAGTGACTG 5 AGCTTCCCTC CCGTGTGTTC TCCGTCCCTG CCCCAGCAAG ACAACTTAGA TCTCCAGGAG AACTGCCATC CAGCITTGGT GCAATGGCTG AGTGCACAAG TGAGTTGTTG CCCTGGGTTT CTTTAATCTA TTCAGCTAGA ACTTTGAAGG ACAATTTCTT GCATTAATAA AGGTTAAGCC CTGAGGGGTC CCTGATAACA ACCTGGAGAC CAGGATTTTA TGGCTCCCCT CACTGATGGA CAAGGAGGTC TGTGCCAAAG AAGAATCCAA TAAGCACATA TTGAGCACTT GCTGTATATG CAGTATTGAG CACTGTAGGC AAGACCCAAG AAAGAGAAGG AGCCATCTCC 10 ATCTTGAAGG AACTCAAAGA CTCAAGTGGG AACGACTGGG CACTGCCACC ACCAGAAAGC TGTTCGACGA GACGGTCGAG CAGGGTGCTG TGGGTGATAT GGACAGCAGA AGGGGGAGAC CAAGGTTCCA GCTCAACCAA TAACTATrGC ACAACCACCT GTCCCTGCCT CAGTTCCCTT TTATGTAACA TGAAGTCGTT GTGAGGGTTA AAGGCAGTAA CAGGTATAAA GTACTTAGAA AAGCAAAGGG TGCTACGTAC ATGTGAGGCA TCATTACGCA GACGTAACTG GGATATGTTr ACTATAAGGA AAAGACACTG AGGTCTAGAA ATAGCTCCGT GGAGCAGAAT 15 CAGTATTGGG AGCCGGTGGC GGTGTGAAGC ACCAGTGTCT GGCACACAGT AGGTGCTCAT TGGCTCCCTT CCACCTGTCA TTCCCACCAC CCTGAGGCCC CAACCGCCAC ACACACAGGA GCATTTGGAG AGAAGGCCAT GTCTTCAAAG TCTGATTGT GATGAGGCAG AGGAAGATAT TTCTAATCGG TCTTGCCCAG AGGATCACAG TGCTGAGACC CCCCACCACC AGCCGGTACC TGGGAAGGGG GAGAGTGCAG GCCTGCTCAG GGACTGTTCC TGTCTCAGCA ACCAAGGGAT TGTTCCTGTC AATCAATGGT TTATTGGAAG GTGGCCCAGT ATGAGCCCTA 20 GAAGAGTGTG AAAAGGAATG GCAATGGTGT TCACCATCGG CAGTGCCAGG GCAGCACTCA TTCACTTGAT AAATGAATAT TTATTAGCTG GTTGGAGAGC TAGAACCTGG AGAGCTAGAA CCTGGAGAAC TAGAACCTGG AGGGCTAGAA CCTGGAGAGG CTAGAACCAA GAAGGGCTAG AACCTGGAGG GGCTAGAACC TAGAGAAGCT AAAACCTGAG CTAGAAGCTG GAGGACTAGA ACCTGGAGGG CTGGAATCTG AAGGGCTAGA ACCTGGAGGG CTGGAATCTG GAGAGCTAGA ACCTGGAGGG CTAGAACCTG GAGGGCTAGA ACCTAGAAGG GCTAGAACCT 25 GGAGGGCTGG AATCTGGAGA GCTAGAACCT GGAGGGCTAG AACCTGGAGG GCTAGAACCT AGAAGGGCTA GAACCTGGAG GGCTAGAACC TGGCAGGTTA GAACCTAGAA GGGCTAGAAC CTGGAGAGCC AGAACCTGGA GGGCTAGAAC CTGGAAGGGC TAGAACCTGT AGAGCTAGAA CATGGAGAGC TAGAACCCGG CAGGCTAGAA CCTGGCAAGC TAGAACCTGG AGGGAATGAA CCTGGAGGGC TAGAACCTGG AGAATGAGAA AAATTTACAT GGCAAAGAGC CCATAAATCC TGACCAATCC AACTCTGAAT TAAAGCAA AAGCGTGAAA AAAAAGATTC 30 CCTCCTTACC CCCAACCCAC TCTTTTCC CACCACCCAC TCTCCTCTGC CTCAGTAAGT ATCTGGAGGA AGAAAACAGG TGAAAGAAGA AGTAAAAACC ATTAGTATT AGTATTAGAA TGAAGTCAAA CTGTGCCACA CATGGTGAAT GAAAAAAAAA AAAAAGAGGC TGTGTTGT CACACAGGGC AGTCATTCAG CACCAGAGCA CGTGATGGTC TGAGACTCTC TTAGGAGCAG AGCTCTGCCG CAATGGCCAT GTGGGGATCC ACACCTGGTC TGAGGGGCAA CTGAGTCTGC GGGAGAAGAG CGGCCCTATG CATGGTGTAG ATGCCCTGAT AAAGAACATC 35 TGTCCTGTGA AAGACTCAAT GAGCTGTTAT GTTGTAAACA GGAAGCA'TT CACATCCAAA CGAGAAAATC ATGTAAACAT GTGTCTTTTC TGTAGAGCAT AATAAATGGA TGAGGTT GCAAAAAAAA AAAAAAAAA AAATGATAGA CCGTCAATAA TTTGTFAAAT GCTTTTAAA ATGAATGCTT TAAGCCGGGT GCAGTGCCTC ACATCTGTAA TCCCAGCACT TTGGAGCCGA GCGGGTGGAT TGTGTGAGGT CAGGAGTTCG AGACCAACCT GGCCAACATG GCAAAACCTC ACTCTCTACC AAAAATACAA AAATTAGCCA GGCATGGTGG CAGGCACCTG 40 TGATCCCAGC TACTCAGGAG GCTGAGACAG GAGAATCGCT TGAACCCGGG AGGCAAGGTT GCAGTGAGCC AAGATTACGC CATTGTACTC CAGCCTGGGT GACAGAGAGA GACTCCGTCT CAAAAAAAAA AAAAAAAAAA AAAAAATTAC GCTTCAAACA CATGATCTCT CACCACTGTT GAATTCTT TCTATGAGCC CAGGAGGGCC TCTCAGAGAG GAAAGCTCCT AGGTCTTCCT TTCCCTCTGC AAACTCCCTG CCTTGAAGGT TCAGAAGGAC TGTGCGTGCT CGTTGCATCC TTTGCAAGTG TCCAAACCCT GATCCCAGCT GTGCTTAGGG GTTCCTGCAA 45 ACCTTTCCA GGTGTTAATT ACCTCCCACT TCATTCCTG TTTACCAACT CAGCTTTTG TTTTAGTGTG TTGAATTCC CTGAACTGAC CGTTGTCTGA TCTCCACCTC CCAACTGAAT TAGGGGAGCT GGGCTTCTGG AAACCCAGGT GCCGGGTGTT GCAGAGTGGC TGAAAGCTGG GATGTGGCAG ATCCGTGGCT ACATTCATGC ACACACACAC ACCCACATAC CCACACATGC ACACACACAC ACACACCCGC ACTCACACAC TTGGACATGC ATAGACCACA GCTTCCACA CCCTTCCTAG ACAGGGGTCA CTTGGTATCC TGGAGAGAGT GTGAAGTCCT 50 GGAATGGAAA GAGGGGGGAT TAAGCCCCAC CTCTAGCCAT GGGACTGAGA CAAGTCACCA CCAACCCATC TGCGCCTTGT TTACCTCCTC TGTGAGGCAA GCACAGAGCC CATGCCTGCC CCCCTGGATG GGAGTGATGT GAAACTTGAA GGGCGGTCAG AGCAAGGGTC GGGAATGGAA GGCCCTTGGG AAAAAAGGCC CTTTCAACTA GGGGCACAGA GGAGGCCCTG GGCTGAGAAC TTGACAGCAC CTTGTAATTG GTAAGCCAAG CCCGAAGGGA CTGGAAATAC TCAGATGTGT CTGTCTCCCT TATTAGGTTC AAAGTCCCTC AAGACCCTGT CTCCATCACA 55 GTGCTCCAGT CCAGACCCCT CCTCTGAGCT CCAGACCCTG CTGGACCCAA CCAGCCCTAT GGGGTCGCAT CCCCACCTGC CTGGAATTCT CCAAAGAACC TCCCCTTTAA CAGTTCCAGC CTTTAACAGT TCCAGTCTAA ACACATGACC TTTCTCCTCT AAATCAGCCC CCCATCTCTG CCTTTGCAGG AGATGGAAGC CATGACACCT GCCTCGCCCC TGTCCTCACC CCATCCATGT CCAATCAAGC ACTAGGCATG TCAGGTTTAC CCTCTAAACT CCTCTGGAAT CCAGTCTCTC AGTCTCCATC ATCCCAGGTC GAAGCTAATG GGCTAACTGG TCCTTGCTrC 60 CACTCTACCC CCACTGCAGT CCTGACTTCC TGAGCAGCAG CCAGGGCCTA ATCGATATTC ACACCAAGCG CCAACCTGAC TGAGATATCC TCCTGCACCA TCATCCCTCC ACCCTGTA GTTCTGCTCA CCCTCAGTGT TCTCATCAAT AATCCACTCC CCTCACAGGC GCGTTTGGGA CCCCATGTTC TATGCTCTCA CAGGACCTTT TGCTTGATTT TTCACTGTAC TTAGGTCAGT TrGCAGTTAT TAAGTGACTG AGCAATGTCT GGCTTCTCCA GTAGACTGTC AGCTCCTAGC CATTGTATAC CTAGCACCGC TGTGTGGGAG CACGTGACAA ACGTCCAGTG 65 AGTCAGGGAC TCAGCAGTCT CCATTTCTCC GCCCTGCTGG AGAATGCGTG TATTTGGCAA TCCCCAGCCC CTGTGCCATC TAACCATCTT TTCTTCTCTG T7CAGCCCAG GTGTGGCCTC ACTCACATCC CACTCTGAGT WO 00/62736 PCT/USOO/08020 274 CCAAATGTTC TCTCCCTGGA AGATATCAAT GTTTCTGTCT GTTCGTGAGG ACTCCGTGCC CACCACGGCC TCTTTCAGGT GAGTCAAAGG GATTCCTCAG TTCACTAGTT AGGGGAGGTG GGCAGACACC CTGGAGAACT CCCTGGAAAG CTCAACTCTC ATGCCCCGGA CAACAGTTGA AGGAACCATG GTGATGTTAA GCCCAAAGAC AAAACCTCTC AGGTGTCCAA GTCCCTGTTG GAATCTTGGG AGCAGAGGGA ATGTTCTGTG GTCTAGAGGA 5 AGAGGGGCTC AGGGAGGAGA AGGGCACATr CCTGGTTGTT ATATGTTTCT ATCTATCCCA GATGAACTTG GAAGTGAAGG GAAGAGAGTT AAACATTAAA GTAAATACCC AGTGGATCAG ACAGCAATGT GCCAGATTGC CTTGGAAACA AAATATCTCC AACACATGGC TGACATTGG TGGGAGATCA GAACACCCTA AAGAGAGAAT TTAAGGGGAG GGGGAGGAGG ACCTGAGCCA GAGTAGAAGC AGAGGATAGG GAGATCTGT CTTGGGGACA GCATTGCAA GAAACAAGGC TGAGGGGTCC ACTCCAACCT CTCCACCCTG CTGCAGGTGC TGCCTATGAT 10 GAAGATGAGC AGATGGCCAT CTCAGCTGGG GCCACAGTGC ACTGGACCTA TAGTTTCCAA TTCCGCACTC AGCAGGCATC TTTCTGATGA TCCGATGGCT TCTCAGAGCC AGGGATGGGC CAGGATCCAT CCCCTTGGCT ACTGTCTTGC TGAGAAATTT ATAAGCAGCA TCTGGTGCTA TACTTGGTC TCTAGTGAGT TAGCTCATGA AAGATGATAG ACTCTCCAAG CCAGGGGTAT GCAGGAAATG GGTTCTGT AGCTACAGAA ATGGGGTTGA GGGTTGGACC AAGGGACTAC CCAGGGGAAG TCTTACCTTC AGAGGACTCT GGAAAGGAGG CTGCAAGTTT 15 TCATGGGTCA AGAATTCAGA GCCCAGTAGA GACAGCTTAT CTCTGTTCCA AGATGTCTGG GGCCTTGGTT GGAAGATTCA AAGGCTAGGA AACCAGGAGC CACCAAAAGC GTAACTGGGG CCAGAGGATC CACTTTCAAG GTGGCAAGTT GGTTCCCCCC ATGTGGCTGC TTGAGTATCC TCACATGGCG GCTCACATCC TTCCAAGTAA GCAATGCAAA AGGCCAAGAA AGATGCTGCA AAGATGTTAT GACCTAGCCT CAGAAATCAC ACACCATCCC TGCCACCATT AGTAAGAAGT CCAGCCCACG TCCAGGAGAA GAGGAAGCAG ATTCCTCCTT TTGAAATGAA 20 GAATATCAAG TAATTCGGGG GGCATATGAA AGCCACCACA CACCACAGGG ATCTTTTTAG AGCATACTTC TTATACCATC ACTGTAGTTC CTTAAGACTC AGGGGCAAAG CCTCACTTCC TTAGCACCCA GTGAAGACCA CGCT7ACTCC CTCACTCAAC CTCTTGCTAC TTCCCACCTC TCCTGTCCAA CATCTAGTGT CACTTTCCAG AACATACCAA CAGCTTCCCC AGTTCTGTGC CTCTGCTCAG GCTGTTCCCC CTGCCTGGTC CACTTGTCCT CCTTCTTGTC CGGTCAAAAT GCTTCTTATC CTTCAAGACC CAGCTCTAGA GTCACCTCCA ACCCCTTACC 25 CACCAGCCCC CTCTCCAAGT CTGTGTCCCA CAACCCCCCT GCTCCCTCCA GGGCACCCTC CACCCTCTGG GCCACAGTTG TCAGGAGTCA GGCAGGGCAG GGGCCGGGTG GTGTCTTCTT TGTGTTCTTG CACTCAGGGC AGAGCTCAGC ACAGAGCAGA CGCTCAAAAA ACATTTAAAG GATAGAAGCA TTGATTTGTG GGTCCCCCAG TCTGGCTCCA GGATGCCAGC CAGCTGCTCC TAGAAGCAAA CGGACTTC CTGGGAAATC CCAGAGGTGA TGATCAGTAA TCTCTCCCGT GACTCGTAGT TCAGCTCTTC CTCCATGAGC CTGACTATCA GTGGACCTTC 30 CAGAAAGAGC CCC'TTCCT TCTCTCACCC ACAGCACAGG GCACTGGGAA AATGCCCAAT GAGTCCTGCC TCTGGGTTGT GCTTTGGACT TTTCAGTGTG TCTCGCATCC ACTCTTCAAC TTGAATGTTG CAACAGCCAT GAAAAAAGAA ATGCAAAGCG ATTCAGGATG AGAGCAATAC CCTACTCCAA AGAAGGCAAC ATAGAAGCTC AGAGAGATCA AGCAATTTGC CCAAGACCAC ACAGCTAGGA GTGGAACTCA TGGCTGTCCA AGCCCCATGC CTCTGCTGAA GGTAGAGATG AATTACAGCA ACAAGTCTAG AAAGGTGCCT GCCCTATGGT CTGTGAGTCT 35 TGCCTAAGAA TGAAAGAGGA GCCAGTGGGT TAAAGATGAG GTCACCAACA ACGGTGGTGT TGGAGTTTAC CACTGATAAT AAGGGTGCAA AATGTAAATT ACTAATGT ATTGAGCCTA GTGCAGTGCG TGGGGCAT17 TGCACATTGT CTCTGATCCC TATGACAACC CTGAGAGGTA GTGGTTAA CTGCCATGTT ACAGGTGAGG TCATTGTGGT TCAAGGACGT TAAGTAACTT CCCCAGCGTG ACACGGCTTA TAAGTAAGGC AGCCAGGATG TGAACCCAGT AGGACTATCT GGCTGCAAAG TCCCCACCCC CCTCGCCATC TGTATCCTCC AATCACTTCA 40 GTGCTTGCT GCATAGAAGG TAACGGAAAT CACGATGCCA CAGACTGTCC AGGAAGACAG AAACTAGGCA GATGGGCTGG CCATGGTCTC CAAGCCAGAC TGGAATCTCC AGGTCTGGAA TGATATCATT TTTCTCTTTT AATAAATTAA CTCACCCACC ACACGGCT GAGAGGCTCA AAGTTGACCA ACTCCCTTGG GAGGGCCCCG GTTGATAAGG AAGGAACGTG AATCCTCCCA TCACGGAAGC TTCAAGGAGG TCAAGGGTCC AACACTTGAG ATTGTTAGTG CTGTTGGTGG ATACTGGCCA AGGAAATATC CCAGTGGAGC CTCGAGATGA AGAACATGAG 45 GCCCCCGTTT AGAACCAAGG ATCAGAGGGG GCTCTGTAAG ACCCAGGGGA GTCAGGTGCA CTGGAGCGCG GGCATGCAGA AAACAGCCTG AGCTCCACCT CGGCTTCTCC TTGTCCTGGC TGGTTGTCCT TAACCCCTGT CTCCTTCTGG ACCAGTTTTT GTCCTTCCCT TGTGACCGCT GAGGGGTAAC AGCCTCTTTC CACTTTCTTT CAGCGCCGAC ATGCTCAATG TCACCTTGCA AGGGCCCACT CTTAACGGGA CCTTTGCCCA GAGCAAATGC CCCCAAGTGG AGTGGCTGGG CTGGCTCAAC ACCATCCAGC CCCCCTTCCT CTGGGTGCTG TTCGTGCTGG 50 CCACCCTAGA GAACATCTT GTCCTCAGCG TCTTCTGCCT GCACAAGAGC AGCTGCACGG TGGCAGAGAT CTACCTGGGG AACCTGGCCG CAGCAGACCT GATCCTGGCC TGCGGGCTGC CCTTCTGGGC CATCACCATC TCCAACAACT TCGACTGGCT CTTTGGGGAG ACGCTCTGCC GCGTGGTGAA TGCCATTATC TCCATGAACC TGTACAGCAG CATCTGTTTC CTGATGCTGG TGAGCATCGA CCGCTACCTG GCCCTGGTGA AAACCATGTC CATGGGCCGG ATGCGCGGCG TGCGCTGGGC. CAAGCTCTAC AGCTTGGTGA TCTGGGGGTG TACGCTGCTC 55 CTGAGCTCAC CCATGCTGGT GTTCCGGACC ATGAAGGAGT ACAGCGATGA GGGCCACAAC GTCACCGCTT GTGTCATCAG CTACCCATCC CTCATCTGGG AAGTGTTCAC CAACATGCTC CTGAATGTCG TGGGCTTCCT GCTGCCCCTG AGTGTCATCA CCTTCTGCAC GATGCAGATC ATGCAGGTGC TGCGGAACAA CGAGATGCAG AAGTTCAAGG AGATCCAGAC GGAGAGGAGG GCCACGGTGC TAGTCCTGGT TGTGCTGCTG CTATTCATCA TCTGCTGGCT GCCCTTCCAG ATCAGCACCT TCCTGGATAC GCTGCATCGC CTCGGCATCC TCTCCAGCTG 60 CCAGGACGAG CGCATCATCG ATGTAATCAC ACAGATCGCC TCCTTCATGG CCTACAGCAA CAGCTGCCTC AACCCACTGG TGTACGTGAT CGTGGGCAAG CGCTTCCGAA AGAAGTCTTG GGAGGTGTAC CAGGGAGTGT GCCAGAAAGG GGGCTGCAGG TCAGAACCCA TTCAGATGGA GAACTCCATG GGCACACTGC GGACCTCCAT CTCCGTGGAA CGCCAGATTC ACAAACTGCA GGACTGGGCA GGGAGCAGAC AGTGAGCAAA CGCCAGCAGG GCTGCTGTGA ATTTGTGTAA GGATTGAGGG ACAGTTGCTT TTCAGCATGG GCCCAGGAAT GCCAAGGAGA 65 CATCTATGCA CGACCTTGGG AAATGAGTTG ATGTCTCCGG TAAAACACCG GAGACTAATT CCTGCCCTGC CCAATTGC AGGGAGCATG GCTGTGAGGA TGGGGTGAAC TCACGCACAG CCAAGGACTC CAAAATCACA WO 00/62736 PCT/USOO/08020 275 ACAGCA'TTAC TGTTCTTATT TGCTGCCACA CCTGAGCCAG CCTGCTCCTT CCCAGGAGTG GAGGAGGCCT GGGGGCAGGG AGAGGAGTGA CTGAGCTTCC CTCCCGTGTG TTCTCCGTCC CTGCCCCAGC AAGACAACTT AGATCTCCAG GAGAACTGCC ATCCAGCT GGTGCAATGG CTGAGTGCAC AAGTGAGTTG TTGCCCTGGG TTTCTTTAAT CTATTCAGCT AGAAC'TGA AGGACAAT CTTGCATTAA TAAAGGTTAA GCCCTGAGGG 5 GTCCCTGATA ACAACCTGGA GACCAGGATT TTATGGCTCC CCTCACTGAT GGACAAGGAG GTCTGTGCCA AAGAAGAATC CAATAAGCAC ATATTGAGCA CTTGCTGTAT ATGCAGTATT GAGCACTGTA GGCAAGAGGG AAGAAAGAGA AGGAGCCATC TCCATCTTGA AGGAACTCAA AGACTCAAGT GGGAACGACT GGGCACTGCC ACCACCAGAA AGCTGTTCGA TGAGACGGTC GAGCAGGGTG CTGTGGGTGA TATGGACAGC AGAAGGGGGA GCCAGGTTCC AGCTCACCAA TACTATTGCA CACCACCTGT CCTGCCTC TGATCCTATC ACAACCTGAG 10 AGTAGTTTTT ACTCCATTTA CAGGTGAGGT CATTGTGGTT CAAGGACGTT AAGTAACTTC CCCAGCTCAC ACGGCTTATA AGTAAGGCAG CCAGGATGTG AACCCAGTAG GACTATCTGG CTGCAAAGTC CCCACCCTCC CTCGCCATCT GTATCCTCCA ATCATCTTCA GTGCTTTGCT GATAGAAGGT ACGGAAATAC GATGCCACAG ACTGTCCAGG AAGACAGAAA CTAGGCAGAT GGGCTGGCCA TGGTCTCCAA GCCAGACTGG AATCTCCAGG TCTGGAATGA TATCATT CTCTTTAAT AAATTAACTC ACCCACCACA CGGCTTTGAG AGGCTCAAAG 15 GTGACCAACT CCCTTGGGAG GGCCCCGGTT GATAAGGAAG GAATGTGAAT CCTCCCATCA CGGAAGCTTC AAGGAGGTCA AGGGTCCAAC ACTTGAGATT GTTAGTGCTG TTGGTGGATA CTGCAGAATA TCCAGTGGAG CCTCAGATGA AGAACATGAG GCCCCGTTTA GATCCAAGGA TCAGAGGGGG CTCTGTAAGA CCCAGGGGAG TCAGGTGCAC TGGAGCGCGG GCTGCAGAAA ACAGCCTGAG CTCCACCTCG GCTrCTCCTIT GCCCTGGCTG GTTGTCCTTA ACCCCTGTCT CCTTCTGGAC CAGTTTGT CCTTCCCTTG TGACCTGAGG GGTAACAGCC 20 TCTTTTCCAC TTTCTTCAG CGCCGACATG CTCAATGTCA CCTTGCAAGG GCCCACTCTT AACGGGACCT TTGCCCAGAG CAAATGCCCC CAAGTGGAGT GGCTGGGCTG GCTCAACACC ATCCAGCCCC CCTTCCTCTG GGTGCTGTTC GTGCTGGCCA CCCTAGAGAA CATCTGTC CTCAGCGTCT TCTGCCTGCA CAAGAGCAGC TGCACGGTGG CAGAGATCTA CCTGGGGAAC CTGGCCGCAG CAGACCTGAT CCTGGCCTGC GGGCTGCCCT TCTGGGCCAT CACCATCTCC AACAACTTCG ACTGGCTCTT TGGGGAGACG CTCTGCCGCG TGGTGAATGC 25 CATTATCTCC ATGAACCTGT ACAGCAGCAT CTGTTCCTG ATGCTGGTGA GCATCGACCG CTACCTGGCC CTGGTGAAAA CCATGTCCAT GGGCCGGATG CGCGGCGTGC GCTGGGCCAA GCTCTACAGC TTGGTGATCT GGGGGTGTAC GCTGCTCCTG AGCTCACCCA TGCTGGTGTT CCGGACCATG AAGGAGTACA GCGATGAGGG CCACAACGTC ACCGCTTGTG TCATCAGCTA CCCATCCCTC ATCTGGGAAG TGTTCACCAA CATGCTCCTG AATGTCGTGG GCTTCCTGCT GCCCCTGAGT GTCATCACCT TCTGCACGAT GCAGATCATG CAGGTGCTGC 30 GGAACAACGA GATGCAGAAG TTCAAGGAGA TCCAGACGGA GAGGAGGGCC ACGGTGCTAG TCCTGGTTGT GCTGCTGCTA TTCATCATCT GCTGGCTGCC CTTCCAGATC AGCACCTTCC TGGATACGCT GCATCGCCTC GGCATCCTCT CCAGCTGCCA GGACGAGCGC ATCATCGATG TAATCACACA GATCGCCTCC TTCATGGCCT ACAGCAACAG CTGCCTCAAC CCACTGGTGT ACGTGATCGT GGGCAAGCGC TrCCGAAAGA AGTCTTGGGA GGTGTACCAG GGAGTGTGCC AGAAAGGGGG CTGCAGGTCA GAACCCATTC AGATGGAGAA CTCCATGGGC 35 ACACTGCGGA CCTCCATCTC CGTGGAACGC CAGATTCACA AACTGCAGGA CTGGGCAGGG AGCAGACAGT GAGCAAACGC CAGCAGGGCT GCTGTGAATT TGTGTAAGGA TTGAGGGACA GTTGCT1TC AGCATGGGCC CAGGAATGCC AAGGAGACAT CTATGCACGA CCTTGGGAAA TGAGTGTTGA TGTCTCCGGT AAAACACCGG AGACTAATTC CTGCCCTGCC CAATTCGA GGGAGCATGG CTGTGAGGAT GGGGTGAACT CACGCACAGC CAAGGACTCC AAAATCACAA CAGCATTACT GTTCTATTT GCTGCCACAC CTGAGCCAGC CTGCTCCTTC 40 CCAGGAGTGG AGGAGGCCTG GGGGAGGGAG AGGAGTGACT GAGCTTCCCT CCCGTGTGTT CTCCGTCCCT GCCCCAGCAA GACAACTTAG ATCTCCAGGA GAACTGCCAT CCACGTTTGG TGCAATGGCT GAGTGCACAA GTGAGTTGTT GCCCTGGGTT TCTTTAATCT ATCAGCTAGA ACTTTGAAGG ACAATTTCTT GCATTAATAA AGGTTAAGCC CTGAGGGGTC CCTTGATAAC AACCTGGAGA CCAGGATTTT ATGGCTCCCC TCACTGATGG ACAAGGAGGT CTGTGCCAAA GAAGAATCAA TAAGCACATA TGAGCACTTC TGTATATCAG TATTGAGCAC 45 TGTAGGCA ATGTTCTCTC CCTGGAAGAT ATCAATGTTT CTGTCTGTTT GTGAGGACTC CGTGCCCACC ACGGCCTCTT TCAGCGCCGA CATGCTCAAT GTCACCTTGC AAGGGCCCAC TCTTAACGGG ACCTTTGCCC AGAGCAAATG CCCCCAAGTG GAGTGGCTGG GCTGGCTCAA CACCATCCAG CCCCCCTTCC TCTGGGTGCT GTTCGTGCTG GCCACCCTAG AGAACATCTT TGTCCTCAGC GTCTTCTGCC TGCACAAGAG CAGCTGCACG GTGGCAGAGA TCTACCTGGG GAACCTGGCC GCAGCAGACC TGATCCTGGC CTGCGGGCTG CCCTTCTGGG 50 CCATCACCAT CTCCAACAAC TTCGACTGGC TCTTTGGGGA GACGCTCTGC CGCGTGGTGA ATGCCATTAT CTCCATGAAC CTGTACAGCA GCATCTGTTT CCTGATGCTG GTGAGCATCG ACCGCTACCT GGCCCTGGTG AAAACCATGT CCATGGGCCG GATGCGCGGC GTGCGCTGGG CCAAGCTCTA CAGCTTGGTG ATCTGGGGGT GTACGCTGCT CCTGAGCTCA CCCATGCTGG TGTTCCGGAC CATGAAGGAG TACAGCGATG AGGGCCACAA CGTCACCGCT TGTGTCATCA GCTACCCATC CCTCATCTGG GAAGTGTTCA CCAACATGCT CCTGAATGTC 55 GTGGGCTTCC TGCTGCCCCT GAGTGTCATC ACCTCTGCA CGATGCAGAT CATGCAGGTG CTGCGGAACA ACGAGATGCA GAAGTTCAAG GAGATCCAGA CGGAGAGGAG GGCCACGGTG CTAGTCCTGG TTGTGCTGCT GCTATTCATC ATCTGCTGGC TGCCCTTCCA GATCAGCACC TTCCTGGATA CGCTGCATCG CCTCGGCATC CTCTCCAGCT GCCAGGACGA GCGCATCATC GATGTAATCA CACAGATCGC CTCCTTCATG GCCTACAGCA ACAGCTGCCT CAACCCACTG GTGTACGTGA TCGTGGGCAA GCGCTTCCGA AAGAAGTCTT GGGAGGTGTA 60 CCAGGGAGTG TGCCAGAAAG GGGGCTGCAG GTCAGAACCC ATTCAGATGG AGAACTCCAT GGGCACACTG CGGACCTCCA TCTCCGTGGA ACGCCAGATT CACAAACTGC AGGACTGGGC AGGGAGCAGA CAGTGAGCAA ACGCCAGCAG GGCTGCTGTG AATTTGTGTA AGGATTGAGG GACAGTTGCT T ATGTTCTCTC CCTGGAAGAT ATCAATGTTT CTGTCTGTTC GTGAGGACTC CGTGCCCACC ACGGCCTCTT TCAGCGCCGA CATGCTCAAT GTCACCTTGC AAGGGCCCAC TCTTAACGGG ACCTTTGCCC AGAGCAAATG CCCCCAAGTG GAGTGGCTGG 65 GCTGGCTCAA CACCATCCAG CCCCCCTTCC TCTGGGTGCT GTT7CGTGCTG GCCACCCTAG AGAACATCTT TGTCCTCAGC GTCTTCTGCC TGCACAAGAG CAGCTGCACG GTGGCAGAGA TCTACCTGGG GAACCTGGCC WO 00/62736 PCT/USOO/08020 276 GCAGCAGACC TGATCCTGGC CTGCGGGCTG CCCTTCTGGG CCATCACCAT CTCCAACAAC TTCGACTGGC TCTTTGGGGA GACGCTCTGC CGCGTGGTGA ATGCCATTAT CTCCATGAAC CTGTACAGCA GCATCTGTTT CCTGATGCTG GTGAGCATCG ACCGCTACCT GGCCCTGGTG AAAACCATGT CCATGGGCCG GATGCGCGGC GTGCGCTGGG CCAAGCTCTA CAGCTTGGTG ATCTGGGGGT GTACGCTGCT CCTGAGCTCA CCCATGCTGG 5 TGTrCCGGAC CATGAAGGAG TACAGCGATG AGGGCCACAA CGTCACCGCT TGTGTCATCA GCTACCCATC CCTCATCTGG GAAGTGTTCA CCAACATGCT CCTGAATGTC GTGGGCTTCC TGCTGCCCCT GAGTGTCATC ACCTTCTGCA CGATGCAGAT CATGCAGGTG CTGCGGAACA ACGAGATGCA GAAGTTCAAG GAGATCCAGA CGGAGAGGAG GGCCACGGTG CTAGTCCTGG TTGTGCTGCT GCTATTCATC ATCTGCTGGC TGCCCTTCCA GATCAGCACC TTCCTGGATA CGCTGCATCG CCTCGGCATC CTCTCCAGCT GCCAGGACGA GCGCATCATC 10 GATGTAATCA CACAGATCGC CTCCTrCATG GCCTACAGCA ACAGCTGCCT CAACCCACTG GTGTACGTGA TCGTGGGCAA GCGCTTCCGA AAGAAGTCTT GGGAGGTGTA CCAGGGAGTG TGCCAGAAAG GGGGCTGCAG GTCAGAACCC ATTCAGATGG AGAACTCCAT GGGCACACTG CGGACCTCCA TCTCCGTGGA ACGCCAGATr CACAAACTGC AGGACTGGGC AGGGAGCAGA CAGTGAGCAA ACGCCAGCAG GGCTGCTGTG AATITGTGTA AGGATTGAGG GACAGTTGCT T GCCCTTCAAA GATGAGCTGT TCCCGCCGCC ACTCCAGCTC TGGCTTCTGG 15 GCTCCGAGGA GGGGTGGGGA CGGTGGGGAC ATCAGGCTGC CCCGCAGTAC CAGGGAGCGA CTGAAGTGCC CATGCCGCTT GCTCCGGAGA AGGTGGGTGC CGGGCAGGGG CTGCTCCAGC CGCCTCACCT CTGCTGGGAG GACAAACTGT CCCAGCACAG AGGGAGGGAG GGAGGGCAGG CAGCGGGGAG AAGTTTCCCT GTGGTCGTGG GGAGTT GCCCTrCAAA GATGAGCTGT TCCCGCCGCC ACTCCAGCTC TGGCTTCTGG GCTCCGAGGA GGGGTGGGGA CGGTGGTGAC GGTGGGGACA TCAGGCTGCC CCGCAGTACC AGGGAGCGAC TGAAGTGCCC 20 ATGCCGCTTG CTCCGGAGAA GGTGGGTGCC GGGCAGGGGC TGCTCCAGCC GCCTCACCTC TGCTGGGAGG ACAAACTGTC CCAGCACAGA GGGAGGGAGG GAGGGCAGGC AGCGGGGAGA AGTTrCCCTG TGGTCGTGGG GAGTT GAGCTCTTCA ATATTAGT GAAAGCTATA GATGAGGCTC CATAGGGGAT AAAGCACAGA CACACCTTTT CAGAGGGCTTr GTGGACTCTG GGCAGCCTGT CCATAGACCT CTGTCCCCAA CTGGCAAGTC AGGAAACTCC AGATTAAGGA GCCCCAATGT GGTTGAACAG CCAGGTGCAC AGATGAGTCA ACCACACAGC 25 CAGGCCAGGG AGGGCCTTCA CTCAAGAGCC TACAGCCAGT TCACAGCCAA GCCAGGGCTA GCGCCAGGCC ACCCATAAAC TGATCTGAGA CTCTGTTTCC CTGTCTCCAT GATGATGGGA TCAGGCTTGA TTGCTGGTTT GTAGGCTTGT TATGAATCAA GTCACAGGGA AGAGGAGCTG ATGGGCTGGG GGGACGTCCT CTGGCCCTCC TGTCTCTTCC CCAGATCCAC TGGGCCCACT CTTATCTGTTr CTCTTCTGAA GGAAGGGTTT TAAGGCTTCA AAAAAAAATG TTTTGAAAGT CCCTGCCCTT TCCAGCTCCT ACCGTCTCAG CCCTGGGAGT GTAAAGTGCT 30 GCAGATAGTT AGTAAGTCTT TGAGCAAAAC TGAGAAAGCC AGCCTGAGCC TTGACATGGG AGAAACCTCC GCCATACATC TCCGAAGAAA CGGCCGCGTG TCTCAGGGGA GCGCAAACAC CCGTACCCAG GAAACAGGAC AGCTTCTGCC ACTGTCGCCC TTGGGAGCCG TACGTGGCAT GACAAAGAAA TCCCAGGACT CCGCCTGCCC ACCTGGCCAC CCTCTGTTTA CACCTTCCGC GTAAACGCCC ACTGTTTACA TCCAAAACTC AGACACAAAA TAACCACCTC AAGAAGATAA ATAATGATAA GAAATAAATG TTACGCGAGG CAAATTTATT CACATGGGGC 35 TTCCCAGGCC ACTGTGGT CAGCCGGGAG GGACGTTT GCCGTCCCAC GACTCCAACG GGCAGCCGGG CCTACGCAAA CATGGAAATC TTCCAAGAGC CTCCCTGGCC CCCAGGGCTC AGAGGGTGGC AGAGCGGAGA GCGAAGGTGG CCGCAGCCTT CCCGGCCCCA CAGCCAGCCT GGCTCCAGCT GGGCAGGAGT GCAGAGCTCA GCTGGAGGCG AGGGGGAAGT GCCCAGGAGG CTGATGACAT CACTACCCAG CCCTTCAAAG ATGAGCTGTT CCCGCCGCCA CTCCAGCTCT GGCTTCTGGG CTCCGAGGAG GGGTGGGGAC GGTGGTGACG GTGGGGACAT 40 CAGGCTGCCC CGCAGTACCA GGGAGCGACT GAAGTGCCCA TGCCGCTTGC TCCGGAGAAG GTGGGTGCCG GGCAGGGGCT GCTCCAGCCG CCTCACCTCT GCTGGGAGGA CAAACTGTCC CAGCACAGAG GGAGGGAGGG AGGGCAGGCA GCGGGGAGAA GTCCCTGT GGTCGTGGGG AGTTGGGAAA AGTTCCCT'TC CTTCCGGAGG GAGG -3' (FRAG. NO:2275) (SEQ. ID NO:3018) 5'- GAGCTCTTCA ATATTTTAGT GAAAGCTATA GATGAGGCTC CATAGGGGAT AAAGCACAGA CACACCTTTT 45 CAGAGGGCTT' GTGGACTCTG GGCAGCCTGT CCATAGACCT CTGTCCCCAA CTGGCAAGTC AGGAAACTCC AGATTAAGGA GCCCCAATGT GGTTGAACAG CCAGGTGCAC AGATGAGTCA ACCACACAGC CAGGCCAGGG AGGGCCTTCA CTCAAGAGCC TACAGCCAGT TCACAGCCAA GCCAGGGCTA GCGCCAGGCC ACCCATAAAC TGATCTGAGA CTCTGTTTCC CTGTCTCCAT GATGATGGGA TCAGGCTTGA TTGCTGGTTT GTAGGCTTGT TATGAATCAA GTCACAGGGA AGAGGAGCTG ATGGGCTGGG GGGACGTCCT CTGGCCCTCC TGTCTCTTCC 50 CCAGATCCAC TGGGCCCACT CTTATCTGTT CTCTTCTGAA GGAAGGGTTT TAAGGCTTCA AAAAAAAATG TITTGAAAGT CCCTGCCCTT TCCAGCTCCT ACCGTCTCAG CCCTGGGAGT GTAAAGTGCT GCAGATAGTT AGTAAGTCTT TGAGCAAAAC TGAGAAAGCC AGCCTGAGCC TTGACATGGG AGAAACCTCC GCCATACATC TCCGAAGAAA CGGCCGCGTG TCTCAGGGGA GCGCAAACAC CCGTACCCAG GAAACAGGAC AGCTTCTGCC ACTGTCGCCC TTGGGAGCCG TACGTGGCAT GACAAAGAAA TCCCAGGACT CCGCCTGCCC ACCTGGCCAC 55 CCTCTGTTTA CACCTTCCGC GTAAACGCCC ACTGTTTACA TCCAAAACTC AGACACAAAA TAACCACCTC AAGAAGATAA ATAATGATAA GAAATAAATG TTACGCGAGG CAAATTTATT CACATGGGGC TTCCCAGGCC ACTTTGTGGT CAGCCGGGAG GGACGTT GCCGTCCCAC GACTCCAACG GGCAGCCGGG CCTACGCAAA CATGGAAATC TTCCAAGAGC CTCCCTGGCC CCCAGGGCTC AGAGGGTGGC AGAGCGGAGA GCGAAGGTGG CCGCAGCCTT CCCGGCCCCA CAGCCAGCCT GGCTCCAGCT GGGCAGGAGT GCAGAGCTCA GCTGGAGGCG 60 AGGGGGAAGT GCCCAGGAGG CTGATGACAT CACTACCCAG CCCTTCAAAG ATGAGCTGTT CCCGCCGCCA CTCCAGCTCT GGCTTCTGGG CTCCGAGGAG GGGTGGGGAC GGTGGTGACG GTGGGGACAT CAGGCTGCCC CGCAGTACCA GGGAGCGACT GAAGTGCCCA TGCCGCTTGC TCCGGAGAAG GTGGGTGCCG GGCAGGGGCT GCTCCAGCCG CCTCACCTCT GCTGGGAGGA CAAACTGTCC CAGCACAGAG GGAGGGAGGG AGGGCAGGCA GCGGGGAGAA GTTTCCCTGT GGTCGTGGGG AGTTGGGAAA AGTTCCCTTC CTTCCGGAGG GAGG-3' 65 (FRAG.NO:2275) (SEQ.ID NO:2461) 5'- GCCCTTCAAA GATGAGCTGT TCCCGCCGCC ACTCCAGCTC TGGCTTCTGG GCTCCGAGGA GGGGTGGGGA WO 00/62736 PCT/US00/08020 277 CGGTGGTGAC GGTGGGGACA TCAGGCTGCC CCGCAGTACC AGGGAGCGAC TGAAGTGCCC ATGCCGCTTG CTCCGGAGAA GGTGGGTGCC GGGCAGGGGC TGCTCCAGCC GCCTCACCTC TGCTGGGAGG ACAAACTGTC CCAGCACAGA GGGAGGGAGG GAGGGCAGGC AGCGGGGAGA AGTTTCCCTG TGGTCGTGGG GAGTT -3' (FRAG. NO:2275) (SEQ. ID NO:2460) 5 5'- GCCCTTCAAA GATGAGCTGT TCCCGCCGCC ACTCCAGCTC TGGCTTCTGG GCTCCGAGGA GGGGTGGGGA CGGTGGGGAC ATCAGGCTGC CCCGCAGTAC CAGGGAGCGA CTGAAGTGCC CATGCCGCTT GCTCCGGAGA AGGTGGGTGC CGGGCAGGGG CTGCTCCAGC CGCCTCACCT CTGCTGGGAG GACAAACTGT CCCAGCACAG AGGGAGGGAG GGAGGGCAGG CAGCGGGGAG AAGTTTCCCT GTGGTCGTGG GGAGTT-3' (FRAG.NO:2275)(SEQ. ID NO:2459) 10 5'- ATGTTCTCTC CCTGGAAGAT ATCAATGTTT CTGTCTGTTC GTGAGGACTC CGTGCCCACC ACGGCCTCTT TCAGCGCCGA CATGCTCAAT GTCACCTTGC AAGGGCCCAC TCTTAACGGG ACCTTTGCCC AGAGCAAATG CCCCCAAGTG GAGTGGCTGG GCTGGCTCAA CACCATCCAG CCCCCCTTCC TCTGGGTGCT GTTCGTGCTG GCCACCCTAG AGAACATCTT TGTCCTCAGC GTCTTCTGCC TGCACAAGAG CAGCTGCACG GTGGCAGAGA TCTACCTGGG GAACCTGGCC GCAGCAGACC TGATCCTGGC CTGCGGGCTG CCCTTCTGGG CCATCACCAT 15 CTCCAACAAC TTCGACTGGC TCTTTGGGGA GACGCTCTGC CGCGTGGTGA ATGCCATTAT CTCCATGAAC CTGTACAGCA GCATCTGTTT CCTGATGCTG GTGAGCATCG ACCGCTACCT GGCCCTGGTG AAAACCATGT CCATGGGCCG GATGCGCGGC GTGCGCTGGG CCAAGCTCTA CAGCTTGGTG ATCTGGGGGT GTACGCTGCT CCTGAGCTCA CCCATGCTGG TGTTCCGGAC CATGAAGGAG TACAGCGATG AGGGCCACAA CGTCACCGCT TGTGTCATCA GCTACCCATC CCTCATCTGG GAAGTGTTCA CCAACATGCT CCTGAATGTC GTGGGCTTCC 20 TGCTGCCCCT GAGTGTCATC ACCTTCTGCA CGATGCAGAT CATGCAGGTG CTGCGGAACA ACGAGATGCA GAAGTTCAAG GAGATCCAGA CGGAGAGGAG GGCCACGGTG CTAGTCCTGG TTGTGCTGCT GCTATTCATC ATCTGCTGGC TGCCCTTCCA GATCAGCACC TTCCTGGATA CGCTGCATCG CCTCGGCATC CTCTCCAGCT GCCAGGACGA GCGCATCATC GATGTAATCA CACAGATCGC CTCCTTCATG GCCTACAGCA ACAGCTGCCT CAACCCACTG GTGTACGTGA TCGTGGGCAA GCGCTTCCGA AAGAAGTCTT GGGAGGTGTA CCAGGGAGTG 25 TGCCAGAAAG GGGGCTGCAG GTCAGAACCC ATTCAGATGG AGAACTCCAT GGGCACACTG CGGACCTCCA TCTCCGTGGA ACGCCAGATT CACAAACTGC AGGACTGGGC AGGGAGCAGA CAGTGAGCAA ACGCCAGCAG GGCTGCTGTG AATTTGTGTA AGGATTGAGG GACAGTTGCT T -3' (FRAG. NO:2275) (SEQ. ID NO:2458) 5'- ATGTTCTCTC CCTGGAAGAT ATCAATGTTT CTGTCTGTTT GTGAGGACTC CGTGCCCACC ACGGCCTCTT TCAGCGCCGA CATGCTCAAT GTCACCTTGC AAGGGCCCAC TCTTAACGGG ACCTrGCCC AGAGCAAATG 30 CCCCCAAGTG GAGTGGCTGG GCTGGCTCAA CACCATCCAG CCCCCCTTCC TCTGGGTGCT GTTCGTGCTG GCCACCCTAG AGAACATCTT TGTCCTCAGC GTCTTCTGCC TGCACAAGAG CAGCTGCACG GTGGCAGAGA TCTACCTGGG GAACCTGGCC GCAGCAGACC TGATCCTGGC CTGCGGGCTG CCCTTCTGGG CCATCACCAT CTCCAACAAC TTCGACTGGC TCTTFGGGGA GACGCTCTGC CGCGTGGTGA ATGCCATTAT CTCCATGAAC CTGTACAGCA GCATCTGT CCTGATGCTG GTGAGCATCG ACCGCTACCT GGCCCTGGTG AAAACCATGT 35 CCATGGGCCG GATGCGCGGC GTGCGCTGGG CCAAGCTCTA CAGCTTGGTG ATCTGGGGGT GTACGCTGCT CCTGAGCTCA CCCATGCTGG TGTTCCGGAC CATGAAGGAG TACAGCGATG AGGGCCACAA CGTCACCGCT TGTGTCATCA GCTACCCATC CCTCATCTGG GAAGTGTTCA CCAACATGCT CCTGAATGTC GTGGGCTTCC TGCTGCCCCT GAGTGTCATC ACCTTCTGCA CGATGCAGAT CATGCAGGTG CTGCGGAACA ACGAGATGCA GAAGTTCAAG GAGATCCAGA CGGAGAGGAG GGCCACGGTG CTAGTCCTGG TTGTGCTGCT GCTATTCATC 40 ATCTGCTGGC TGCCCTTCCA GATCAGCACC TTCCTGGATA CGCTGCATCG CCTCGGCATC CTCTCCAGCT GCCAGGACGA GCGCATCATC GATGTAATCA CACAGATCGC CTCCTTCATG GCCTACAGCA ACAGCTGCCT CAACCCACTG GTGTACGTGA TCGTGGGCAA GCGCTTCCGA AAGAAGTCTT GGGAGGTGTA CCAGGGAGTG TGCCAGAAAG GGGGCTGCAG GTCAGAACCC ATTCAGATGG AGAACTCCAT GGGCACACTG CGGACCTCCA TCTCCGTGGA ACGCCAGATT CACAAACTGC AGGACTGGGC AGGGAGCAGA CAGTGAGCAA ACGCCAGCAG 45 GGCTGCTGTG AATTTGTGTA AGGATTGAGG GACAGTTGCT T -3' (FRAG. NO:2275) (SEQ. ID NO:2457) 5'- TGATCCTATC ACAACCTGAG AGTAGTTT ACTCCATTTA CAGGTGAGGT CATTGTGGTT CAAGGACGTT AAGTAACTTC CCCAGCTCAC ACGGCTTATA AGTAAGGCAG CCAGGATGTG AACCCAGTAG GACTATCTGG CTGCAAAGTC CCCACCCTCC CTCGCCATCT GTATCCTCCA ATCATCTTCA GTGCTTTGCT GATAGAAGGT ACGGAAATAC GATGCCACAG ACTGTCCAGG AAGACAGAAA CTAGGCAGAT GGGCTGGCCA TGGTCTCCAA 50 GCCAGACTGG AATCTCCAGG TCTGGAATGA TATCATT CTCTTTAAT AAATTAACTC ACCCACCACA CGGC1TTGAG AGGCTCAAAG GTGACCAACT CCCTTGGGAG GGCCCCGGTr GATAAGGAAG GAATGTGAAT CCTCCCATCA CGGAAGCTTC AAGGAGGTCA AGGGTCCAAC ACTTGAGATT GTTAGTGCTG TTGGTGGATA CTGCAGAATA TCCAGTGGAG CCTCAGATGA AGAACATGAG GCCCCGTTTA GATCCAAGGA TCAGAGGGGG CTCTGTAAGA CCCAGGGGAG TCAGGTGCAC TGGAGCGCGG GCTGCAGAAA ACAGCCTGAG CTCCACCTCG 55 GCTTCTCCTT GCCCTGGCTG GTTGTCCTTA ACCCCTGTCT CCTTCTGGAC CAGTTTTTGT CCTTCCCTTG TGACCTGAGG GGTAACAGCC TCTTTCCAC TTTCTTTCAG CGCCGACATG CTCAATGTCA CCTTGCAAGG GCCCACTCTT AACGGGACCT TTGCCCAGAG CAAATGCCCC CAAGTGGAGT GGCTGGGCTG GCTCAACACC ATCCAGCCCC CCTTCCTCTG GGTGCTGTTC GTGCTGGCCA CCCTAGAGAA CATCTTTGTC CTCAGCGTCT TCTGCCTGCA CAAGAGCAGC TGCACGGTGG CAGAGATCTA CCTGGGGAAC CTGGCCGCAG CAGACCTGAT 60 CCTGGCCTGC GGGCTGCCCT TCTGGGCCAT CACCATCTCC AACAACTTCG ACTGGCTCTT TGGGGAGACG CTCTGCCGCG TGGTGAATGC CATTATCTCC ATGAACCTGT ACAGCAGCAT CTGTTTCCTG ATGCTGGTGA GCATCGACCG CTACCTGGCC CTGGTGAAAA CCATGTCCAT GGGCCGGATG CGCGGCGTGC GCTGGGCCAA GCTCTACAGC TTGGTGATCT GGGGGTGTAC GCTGCTCCTG AGCTCACCCA TGCTGGTGTT CCGGACCATG AAGGAGTACA GCGATGAGGG CCACAACGTC ACCGCTTGTG TCATCAGCTA CCCATCCCTC ATCTGGGAAG 65 TGTTCACCAA CATGCTCCTG AATGTCGTGG GCTTCCTGCT GCCCCTGAGT GTCATCACCT TCTGCACGAT GCAGATCATG CAGGTGCTGC GGAACAACGA GATGCAGAAG TrCAAGGAGA TCCAGACGGA GAGGAGGGCC WO 00/62736 PCT/USOO/08020 278 ACGGTGCTAG TCCTGGTTGT GCTGCTGCTA TTCATCATCT GCTGGCTGCC CTTCCAGATC AGCACCTTCC TGGATACGCT GCATCGCCTC GGCATCCTCT CCAGCTGCCA GGACGAGCGC ATCATCGATG TAATCACACA GATCGCCTCC TTCATGGCCT ACAGCAACAG CTGCCTCAAC CCACTGGTGT ACGTGATCGT GGGCAAGCGC TTCCGAAAGA AGTCTTGGGA GGTGTACCAG GGAGTGTGCC AGAAAGGGGG CTGCAGGTCA GAACCCATTC 5 AGATGGAGAA CTCCATGGGC ACACTGCGGA CCTCCATCTC CGTGGAACGC CAGATTCACA AACTGCAGGA CTGGGCAGGG AGCAGACAGT. GAGCAAACGC CAGCAGGGCT GCTGTGAATT TGTGTAAGGA TTGAGGGACA GTTGCTTTC AGCATGGGCC CAGGAATGCC AAGGAGACAT CTATGCACGA CCTTGGGAAA TGAGTGTTGA TGTCTCCGGT AAAACACCGG AGACTAATTC CTGCCCTGCC CAATTTCGA GGGAGCATGG CTGTGAGGAT GGGGTGAACT CACGCACAGC CAAGGACTCC AAAATCACAA CAGCATTACT GTTCTTATTT GCTGCCACAC 10 CTGAGCCAGC CTGCTCCTTC CCAGGAGTGG AGGAGGCCTG GGGGAGGGAG AGGAGTGACT GAGCTTCCCT CCCGTGTGTT CTCCGTCCCT GCCCCAGCAA GACAACTTAG ATCTCCAGGA GAACTGCCAT CCACGTTTGG TGCAATGGCT GAGTGCACAA GTGAGTTGTT GCCCTGGGTT TCTTTAATCT ATCAGCTAGA ACTTTGAAGG ACAATTTCTT GCATTAATAA AGGTTAAGCC CTGAGGGGTC CCTTGATAAC AACCTGGAGA CCAGGATTT ATGGCTCCCC TCACTGATGG ACAAGGAGGT CTGTGCCAAA GAAGAATCAA TAAGCACATA TGAGCACTTC 15 TGTATATCAG TATTGAGCAC TGTAGGCA -3' (FRAG. NO:2275) (SEQ. ID NO:2456) 5'- CTGCAGAAAA CAGCCTGAGC TCCACCTCGG CTTCTCCTTG CCCTGGCTGG TTGTCCTTAA CCCCTGTCTC CTTCTGGACC AGTT GTC CTTCCCTTGT GACCCTGAGG GGTAACAGCC TCTTTTCCAC TTTCTTTCAG CGCCGACATG CTCAATGTCA CCTTGCAAGG GCCCACTCTT AACGGGACCT TTGCCCAGAG CAAATGCCCC CAAGTGGAGT GGCTGGGCTG GCTCAACACC ATCCAGCCCC CCTTCCTCTG GGTGCTGTTC GTGCTGGCCA 20 CCCTAGAGAA CATCTTTGTC CTCAGCGTCT TCTGCCTGCA CAAGAGCAGC TGCACGGTGG CAGAGATCTA CCTGGGGAAC CTGGCCGCAG CAGACCTGAT CCTGGCCTGC GGGCTGCCCT TCTGGGCCAT CACCATCTCC AACAACTTCG ACTGGCTCTT TGGGGAGACG CTCTGCCGCG TGGTGAATGC CATTATCTCC ATGAACCTGT ACAGCAGCAT CTGTTTCCTG ATGCTGGTGA GCATCGACCG CTACCTGGCC CTGGTGAAAA CCATGTCCAT GGGCCGGATG CGCGGCGTGC GCTGGGCCAA GCTCTACAGC TTGGTGATCT GGGGGTGTAC GCTGCTCCTG 25 AGCTCACCCA TGCTGGTGTT CCGGACCATG AAGGAGTACA GCGATGAGGG CCACAACGTC ACCGCTTGTG TCATCAGCTA CCCATCCCTC ATCTGGGAAG TGTTCACCAA CATGCTCCTG AATGTCGTGG GCTTCCTGCT GCCCCTGAGT GTCATCACCT TCTGCACGAT GCAGATCATG CAGGTGCTGC GGAACAACGA GATGCAGAAG TTCAAGGAGA TCCAGACGGA GAGGAGGGCC ACGGTGCTAG TCCTGGTTGT GCTGCTGCTA TTCATCATCT GCTGGCTGCC CTTCCAGATC AGCACCTTCC TGGATACGCT GCATCGCCTC GGCATCCTCT CCAGCTGCCA 30 GGACGAGCGC ATCATCGATG TAATCACACA GATCGCCTCC TTCATGGCCT ACAGCAACAG CTGCCTCAAC CCACTGGTGT ACGTGATCGT GGGCAAGCGC TTCCGAAAGA AGTCTTGGGA GGTGTACCAG GGAGTGTGCC AGAAAGGGGG CTGCAGGTCA GAACCCATTC AGATGGAGAA CTCCATGGGC ACACTGCGGA CCTCCATCTC CGTGGAACGC CAGATTCACA AACTGCAGGA CTGGGCAGGG AGCAGACAGT GAGCAAACGC CAGCAGGGCT GCTGTGAATT TGTGTAAGGA TTGAGGGACA GTTGCTTITC AGCATGGGCC CAGGAATGCC AAGGAGACAT 35 CTATGCACGA CCTTGGGAAA TGAGTTGATG TCTCCGGTAA AACACCGGAG ACTAATTCCT GNCCTGCCCA ATITTGCAGG GAGCATGGCT GTGAGGATGG GGTGAACTCA CGCACAGCCA AGGACTCCAA AATCACAACA GCATTACTGT TCTTATTGC TGCCACACCT GAGCCAGCCT GCTCCTTCCC AGGAGTGGAG GAGGCCTGGG GGCAGGGAGA GGAGTGACTG AGCTTCCCTC CCGTGTGTTC TCCGTCCCTG CCCCAGCAAG ACAACTTAGA TCTCCAGGAG AACTGCCATC CAGCTTTGGT GCAATGGCTG AGTGCACAAG TGAGTTGTTG CCCTGGGTTT 40 CTTTAATCTA TTCAGCTAGA ACTTTGAAGG ACAATTTCTT GCATTAATAA AGGTTAAGCC CTGAGGGGTC CCTGATAACA ACCTGGAGAC CAGGATTTA TGGCTCCCCT CACTGATGGA CAAGGGAGGT CTGTGCCAAA GAAGAATCCA ATAAGCACAT ATTGAGCACT TGCTGTATAT GCAGTATTGA GCACTGTAGG CAAGAGGGAA GAAAGAGAAG GAGCCATCTC CATCTTGAAG GAACTCAAAG ACTCAAGTGG GAACGACTGG CACTGCCACC ACCAGAAAGC TGTTCGACGA GACGGTCGAG CAGGGTGCTG TGGGTGATAT GGACAGCAGA AGGGGGAGAC 45 CAAGGTTCCA GCTCAACCAA TAACTATTGC ACAACCACCT GTCCCTGCCT CAGTTCCCTC TTCTGTAACA TGAAGTCGTT GTGAGGGTTA AAGGCAGTAA CAGGTATAAA GTACTTAGAA AAGCAAAGGG TGCTACGTAC ATGTGAGGCA TCATTACGCA GACGTAACTG GGATATGTTT ACTATAAGGA AAAGACACTG AGGTCTAGA -3' (FRAG. NO:2275) (SEQ. ID NO:2455) 5'- AAATGATAGA CCGTCAATAA TTTGTTAAAT GCTTTTTAAA ATGAATGCTT TAAGCCGGGT GCAGTGCCTC 50 ACATCTGTAA TCCCAGCACT TTGGAGCCGA GCGGGTGGAT TGTGTGAGGT CAGGAGTrCG AGACCAACCT GGCCAACATG GCAAAACCTC ACTCTCTACC AAAAATACAA AAATTAGCCA GGCATGGTGG CAGGCACCTG TGATCCCAGC TACTCAGGAG GCTGAGACAG GAGAATCGCT TGAACCCGGG AGGCAAGGTT GCAGTGAGCC AAGATTACGC CATTGTACTC CAGCCTGGGT GACAGAGAGA GACTCCGTCT CAAAAAAAAA AAAAAAAAAA AAAAAATTAC GCTTCAAACA CATGATCTCT CACCACTGTT GAATTCTT TCTATGAGCC CAGGAGGGCC 55 TCTCAGAGAG GAAAGCTCCT AGGTCTTCCT TTCCCTCTGC AAACTCCCTG CCTTGAAGGT TCAGAAGGAC TGTGCGTGCT CGTTGCATCC TTTGCAAGTG TCCAAACCCT GATCCCAGCT GTGCTTAGGG GTTCCTGCAA ACCTTTTCCA GGTGTTAATT ACCTCCCACT TCATTTCCTG TTTACCAACT CAGCTTG TTAGTGTG TTTGAATTCC CTGAACTGAC CGTTGTCTGA TCTCCACCTC CCAACTGAAT TAGGGGAGCT GGGCTTCTGG AAACCCAGGT GCCGGGTGTT GCAGAGTGGC TGAAAGCTGG GATGTGGCAG ATCCGTGGCT ACATTCATGC 60 ACACACACAC ACCCACATAC CCACACATGC ACACACACAC ACACACCCGC ACTCACACAC TTGGACATGC ATAGACCACA GCTTTCCACA CCCTTCCTAG ACAGGGGTCA CTTGGTATCC TGGAGAGAGT GTGAAGTCCT GGAATGGAAA GAGGGGGGAT TAAGCCCCAC CTCTAGCCAT GGGACTGAGA CAAGTCACCA CCAACCCATC TGCGCCTTGT TTACCTCCTC TGTGAGGCAA GCACAGAGCC CATGCCTGCC CCCCTGGATG GGAGTGATGT GAAACTTGAA GGGCGGTCAG AGCAAGGGTC GGGAATGGAA GGCCCTTGGG AAAAAAGGCC CTTTCAACTA 65 GGGGCACAGA GGAGGCCCTG GGCTGAGAAC TTGACAGCAC CTTGTAATTG GTAAGCCAAG CCCGAAGGGA CTGGAAATAC TCAGATGTGT CTGTCTCCCT TATTAGGrTTC AAAGTCCCTC AAGACCCTGT CTCCATCACA WO 00/62736 PCT/USOO/08020 279 GTGCTCCAGT CCAGACCCCT CCTCTGAGCT CCAGACCCTG CTGGACCCAA CCAGCCCTAT GGGGTCGCAT CCCCACCTGC CTGGAATTCT CCAAAGAACC TCCCCTTTAA CAGTTCCAGC CTTAACAGT TCCAGTCTAA ACACATGACC TTTCTCCTCT AAATCAGCCC CCCATCTCTG CCTTTGCAGG AGATGGAAGC CATGACACCT GCCTCGCCCC TGTCCTCACC CCATCCATGT CCAATCAAGC ACTAGGCATG TCAGGTTTAC CCTCTAAACT 5 CCTCTGGAAT CCAGTCTCTC AGTCTCCATC ATCCCAGGTC GAAGCTAATG GGCTAACTGG TCCTTGCTTC CACTCTACCC CCACTGCAGT CCTGACTTCC TGAGCAGCAG CCAGGGCCTA ATCGATATTC ACACCAAGCG CCAACCTGAC TGAGATATCC TCCTGCACCA TCATCCCTCC ACCCTGTTTA GTTCTGCTCA CCCTCAGTGT TCTCATCAAT AATCCACTCC CCTCACAGGC GCGTTTGGGA CCCCATGTTC TATGCTCTCA CAGGACCTT TGCTrGATTT TTCACTGTAC TTAGGTCAGT TTGCAGTTAT TAAGTGACTG AGCAATGTCT GGCTTCTCCA 10 GTAGACTGTC AGCTCCTAGC CATTGTATAC CTAGCACCGC TGTGTGGGAG CACGTGACAA ACGTCCAGTG AGTCAGGGAC TCAGCAGTCT CCATTTCTCC GCCCTGCTGG AGAATGCGTG TATTTGGCAA TCCCCAGCCC CTGTGCCATC TAACCATCTT TTCTTCTCTG TTCAGCCCAG GTGTGGCCTC ACTCACATCC CACTCTGAGT CCAAATGTTC TCTCCCTGGA AGATATCAAT GTTTCTGTCT GTTCGTGAGG ACTCCGTGCC CACCACGGCC TCTTTCAGGT GAGTCAAAGG GATTCCTCAG TTCACTAGTT AGGGGAGGTG GGCAGACACC CTGGAGAACT 15 CCCTGGAAAG CTCAACTCTC ATGCCCCGGA CAACAGTTGA AGGAACCATG GTGATGTTAA GCCCAAAGAC AAAACCTCTC AGGTGTCCAA GTCCCTGTTG GAATCTTGGG AGCAGAGGGA ATGTTCTGTG GTCTAGAGGA AGAGGGGCTC AGGGAGGAGA AGGGCACATT CCTGGTTGTT ATATGTTTCT ATCTATCCCA GATGAACTrTG GAAGTGAAGG GAAGAGAGTT AAACATTAAA GTAAATACCC AGTGGATCAG ACAGCAATGT GCCAGATTGC CTTGGAAACA AAATATCTCC AACACATGGC TGACATTTGG TGGGAGATCA GAACACCCTA AAGAGAGAAT 20 TTAAGGGGAG GGGGAGGAGG ACCTGAGCCA GAGTAGAAGC AGAGGATAGG GAGATCTGTT CTTGGGGACA GCATTTGCAA GAAACAAGGC TGAGGGGTCC ACTCCAACCT CTCCACCCTG CTGCAGGTGC TGCCTATGAT GAAGATGAGC AGATGGCCAT CTCAGCTGGG GCCACAGTGC ACTGGACCTA TAGTTCCAA TTCCGCACTC AGCAGGCATC TTTCTGATGA TCCGATGGCT TCTCAGAGCC AGGGATGGGC CAGGATCCAT CCCCTTGGCT ACTGTCTTGC TGAGAAATT ATAAGCAGCA TCTGGTGCTA TACTTTGGTC TCTAGTGAGT TAGCTCATGA 25 AAGATGATAG ACTCTCCAAG CCAGGGGTAT GCAGGAAATG GGTTTTCTGT AGCTACAGAA ATGGGGTTGA GGGTTGGACC AAGGGACTAC CCAGGGGAAG TCTTACCTTC AGAGGACTCT GGAAAGGAGG CTGCAAGTTT TCATGGGTCA AGAATTCAGA GCCCAGTAGA GACAGCTTAT CTCTGTTCCA AGATGTCTGG GGCCTTGGTT GGAAGATTCA AAGGCTAGGA AACCAGGAGC CACCAAAAGC GTAACTGGGG CCAGAGGATC CACTTTCAAG GTGGCAAGTT GGTTCCCCCC ATGTGGCTGC TTGAGTATCC TCACATGGCG GCTCACATCC TTCCAAGTAA 30 GCAATGCAAA AGGCCAAGAA AGATGCTGCA AAGATGTTAT GACCTAGCCT CAGAAATCAC ACACCATCCC TGCCACCATT AGTAAGAAGT CCAGCCCACG TCCAGGAGAA GAGGAAGCAG ATTCCTCCT TTGAAATGAA GAATATCAAG TAATTCGGGG GGCATATGAA AGCCACCACA CACCACAGGG ATCTTTTTAG AGCATACTTC TTATACCATC ACTGTAGTTC CTTAAGACTC AGGGGCAAAG CCTCACTTCC TTAGCACCCA GTGAAGACCA CGCTTACTCC CTCACTCAAC CTCTTGCTAC TTCCCACCTC TCCTGTCCAA CATCTAGTGT CACTITCCAG 35 AACATACCAA CAGCTTCCCC AGTTCTGTGC CTCTGCTCAG GCTGTTCCCC CTGCCTGGTC CACTTGTCCT CCTTCTTGTC CGGTCAAAAT GCTrCTTATC CTTCAAGACC CAGCTCTAGA GTCACCTCCA ACCCCTTACC CACCAGCCCC CTCTCCAAGT CTGTGTCCCA CAACCCCCCT GCTCCCTCCA GGGCACCCTC CACCCTCTGG GCCACAGTTrG TCAGGAGTCA GGCAGGGCAG GGGCCGGGTG GTGTCTTCTT TGTGTTCTTG CACTCAGGGC AGAGCTCAGC ACAGAGCAGA CGCTCAAAAA ACATTTAAAG GATAGAAGCA TTGATTTGTG GGTCCCCCAG 40 TCTGGCTCCA GGATGCCAGC CAGCTGCTCC TAGAAGCAAA CGGACTTTTC CTGGGAAATC CCAGAGGTGA TGATCAGTAA TCTCTCCCGT GACTCGTAGT TCAGCTCTTC CTCCATGAGC CTGACTATCA GTGGACCTTC CAGAAAGAGC CCCTTTTCCT TCTCTCACCC ACAGCACAGG GCACTGGGAA AATGCCCAAT GAGTCCTGCC TCTGGGTTGT GCTTTGGACT TTTCAGTGTG TCTCGCATCC ACTCTTCAAC TTGAATGTTG CAACAGCCAT GAAAAAAGAA ATGCAAAGCG ATTCAGGATG AGAGCAATAC CCTACTCCAA AGAAGGCAAC ATAGAAGCTC 45 AGAGAGATCA AGCAATTTGC CCAAGACCAC ACAGCTAGGA GTGGAACTCA TGGCTGTCCA AGCCCCATGC CTCTGCTGAA GGTAGAGATG AATTACAGCA ACAAGTCTAG AAAGGTGCCT GCCCTATGGT CTGTGAGTCT TGCCTAAGAA TGAAAGAGGA GCCAGTGGGT TAAAGATGAG GTCACCAACA ACGGTGGTGT TGGAGTTTAC CACTGATAAT AAGGGTGCAA AATGTAAATT ACTAATGTTT ATTGAGCCTA GTGCAGTGCG TGGGGCATTT TGCACATTGT CTCTGATCCC TATGACAACC CTGAGAGGTA GTGGTTTTAA CTGCCATGTT ACAGGTGAGG 50 TCATTGTGGT TCAAGGACGT TAAGTAACTT CCCCAGCGTG ACACGGCTTA TAAGTAAGGC AGCCAGGATG TGAACCCAGT AGGACTATCT GGCTGCAAAG TCCCCACCCC CCTCGCCATC TGTATCCTCC AATCACTTCA GTGCTTTGCT GCATAGAAGG TAACGGAAAT CACGATGCCA CAGACTGTCC AGGAAGACAG AAACTAGGCA GATGGGCTGG CCATGGTCTC CAAGCCAGAC TGGAATCTCC AGGTCTGGAA TGATATCATT TTTCTCTTTT AATAAATTAA CTCACCCACC ACACGGCTTT GAGAGGCTCA AAGTTGACCA ACTCCCTTGG GAGGGCCCCG 55 GTTGATAAGG AAGGAACGTG AATCCTCCCA TCACGGAAGC TTCAAGGAGG TCAAGGGTCC AACACTTGAG ATTGTTAGTG CTGTTGGTGG ATACTGGCCA AGGAAATATC CCAGTGGAGC CTCGAGATGA AGAACATGAG GCCCCCGTTT AGAACCAAGG ATCAGAGGGG GCTCTGTAAG ACCCAGGGGA GTCAGGTGCA CTGGAGCGCG GGCATGCAGA AAACAGCCTG AGCTCCACCT CGGCTTCTCC TTGTCCTGGC TGGTTGTCCT TAACCCCTGT CTCCTTCTGG ACCAGTITTTT GTCCTTCCCT TGTGACCGCT GAGGGGTAAC AGCCTCTTTC CACTTTCTTT 60 CAGCGCCGAC ATGCTCAATG TCACCTTGCA AGGGCCCACT CTTAACGGGA CCTTTGCCCA GAGCAAATGC CCCCAAGTGG AGTGGCTGGG CTGGCTCAAC ACCATCCAGC CCCCCTTCCT CTGGGTGCTG TTCGTGCTGG CCACCCTAGA GAACATCTTT GTCCTCAGCG TCTTCTGCCT GCACAAGAGC AGCTGCACGG TGGCAGAGAT CTACCTGGGG AACCTGGCCG CAGCAGACCT GATCCTGGCC TGCGGGCTGC CCTTCTGGGC CATCACCATC TCCAACAACT TCGACTGGCT CTTGGGGAG ACGCTCTGCC GCGTGGTGAA TGCCATTATC TCCATGAACC 65 TGTACAGCAG CATCTGTTTC CTGATGCTGG TGAGCATCGA CCGCTACCTG GCCCTGGTGA AAACCATGTC CATGGGCCGG ATGCGCGGCG TGCGCTGGGC CAAGCTCTAC AGCTTGGTGA TCTGGGGGTG TACGCTGCTC WO 00/62736 PCT/USOO/08020 280 CTGAGCTCAC CCATGCTGGT GTTCCGGACC ATGAAGGAGT ACAGCGATGA GGGCCACAAC GTCACCGCTT GTGTCATCAG CTACCCATCC CTCATCTGGG AAGTGTTCAC CAACATGCTC CTGAATGTCG TGGGCTTCCT GCTGCCCCTG AGTGTCATCA CCTTCTGCAC GATGCAGATC ATGCAGGTGC TGCGGAACAA CGAGATGCAG AAGTTCAAGG AGATCCAGAC GGAGAGGAGG GCCACGGTGC TAGTCCTGGT TGTGCTGCTG CTATTCATCA 5 TCTGCTGGCT GCCCTrCCAG ATCAGCACCT TCCTGGATAC GCTGCATCGC CTCGGCATCC TCTCCAGCTG CCAGGACGAG CGCATCATCG ATGTAATCAC ACAGATCGCC TCCTTCATGG CCTACAGCAA CAGCTGCCTC AACCCACTGG TGTACGTGAT CGTGGGCAAG CGCTrCCGAA AGAAGTCTTG GGAGGTGTAC CAGGGAGTGT GCCAGAAAGG GGGCTGCAGG TCAGAACCCA TTCAGATGGA GAACTCCATG GGCACACTGC GGACCTCCAT CTCCGTGGAA CGCCAGATTC 'ACAAACTGCA GGACTGGGCA GGGAGCAGAC AGTGAGCAAA CGCCAGCAGG 10 GCTGCTGTGA ATTTGTGTAA GGATTGAGGG ACAGTTGCTT TTCAGCATGG GCCCAGGAAT GCCAAGGAGA CATCTATGCA CGACCTTGGG AAATGAGTTG ATGTCTCCGG TAAAACACCG GAGACTAAT CCTGCCCTGC CCAATTTTGC AGGGAGCATG GCTGTGAGGA TGGGGTGAAC TCACGCACAG CCAAGGACTC CAAAATCACA ACAGCATTAC TGTTCTrATT TGCTGCCACA CCTGAGCCAG CCTGCTCCTr CCCAGGAGTG GAGGAGGCCT GGGGGCAGGG AGAGGAGTGA CTGAGCTTCC CTCCCGTGTG TTCTCCGTCC CTGCCCCAGC AAGACAACTT 15 AGATCTCCAG GAGAACTGCC ATCCAGCT GGTGCAATGG CTGAGTGCAC AAGTGAGTrG TTGCCCTGGG TTTCTTTAAT CTATTCAGCT AGAACTTTGA AGGACAATTT CTTGCATTAA TAAAGGTTAA GCCCTGAGGG GTCCCTGATA ACAACCTGGA GACCAGGATT TTATGGCTCC CCTCACTGAT GGACAAGGAG GTCTGTGCCA AAGAAGAATC CAATAAGCAC ATATTGAGCA CTTGCTGTAT ATGCAGTATT GAGCACTGTA GGCAAGAGGG AAGAAAGAGA AGGAGCCATC TCCATCTTGA AGGAACTCAA AGACTCAAGT GGGAACGACT GGGCACTGCC 20 ACCACCAGAA AGCTGTTCGA TGAGACGGTC GAGCAGGGTG CTGTGGGTGA TATGGACAGC AGAAGGGGGA GCCAGGTTCC AGCTCACCAA TACTATTGCA CACCACCTGT CCTGCCTC -3' (FRAG. NO:2275) (SEQ. ID NO:2454) 5'- CAGATTCACA AACTGCAGGA CTGGGCAGGG AGCAGACAGT GAGCAAACGC CAGCAGGGCT GCTGTGAATT TGTGTAAGGA TTGAGGGACA GTTGCTTTTC AGCATGGGCC CAGGAATGCC AAGGAGACAT 25 CTATGCACGA CCTTGGGAAA TGAGTTGATG TCTCCGGTAA AACACCGGAG ACTAATTCCT GCCCTGCCCA ATTTTGCAGG GAGCATGGCT GTGAGGATGG GGTGAACTCA CGCACAGCCA AGGACTCCAA AATCACAACA GCATTACTGT TCTTATTTGC TGCCACACCT GAGCCAGCCT GCTCCTTCCC AGGAGTGGAG GAGGCCTGGG GGGAGGGAGA GGAGTGACTG AGCTTCCCTC CCGTGTGTTC TCCGTCCCTG CCCCAGCAAG ACAACTTAGA TCTCCAGGAG AACTGCCATC CAGCTTTGGT GCAATGGCTG AGTGCACAAG TGAGTrGTTG CCCTGGGTTT 30 CTTTAATCTA TTCAGCTAGA ACTGAAGG ACAATTTCTr GCATTAATAA AGGTTAAGCC CTGAGGGGTC CCTGATAACA ACCTGGAGAC CAGGATTTTA TGGCTCCCCT CACTGATGGA CAAGGAGGTC TGTGCCAAAG AAGAATCCAA TAAGCACATA TTGAGCACTT GCTGTATATG CAGTATTGAG CACTGTAGGC AAGACCCAAG AAAGAGAAGG AGCCATCTCC ATCTTGAAGG AACTCAAAGA CTCAAGTGGG AACGACTGGG CACTGCCACC ACCAGAAAGC TGTTCGACGA GACGGTCGAG CAGGGTGCTG TGGGTGATAT GGACAGCAGA AGGGGGAGAC 35 CAAGGTTCCA GCTCAACCAA TAACTATTGC ACAACCACCT GTCCCTGCCT CAGTTCCCTT TTATGTAACA TGAAGTCGTT GTGAGGGTTA AAGGCAGTAA CAGGTATAAA GTACTTAGAA AAGCAAAGGG TGCTACGTAC ATGTGAGGCA TCATTACGCA GACGTAACTG GGATATGTTT ACTATAAGGA AAAGACACTG AGGTCTAGAA ATAGCTCCGT GGAGCAGAAT CAGTATTGGG AGCCGGTGGC GGTGTGAAGC ACCAGTGTCT GGCACACAGT AGGTGCTCAT TGGCTCCCTr CCACCTGTCA TTCCCACCAC CCTGAGGCCC CAACCGCCAC ACACACAGGA 40 GCATTTGGAG AGAAGGCCAT GTCTTCAAAG TCTGATTGT GATGAGGCAG AGGAAGATAT TTCTAATCGG TCTTGCCCAG AGGATCACAG TGCTGAGACC CCCCACCACC AGCCGGTACC TGGGAAGGGG GAGAGTGCAG GCCTGCTCAG GGACTGTTCC TGTCTCAGCA ACCAAGGGAT TGTTCCTGTC AATCAATGGT TTATTGGAAG GTGGCCCAGT ATGAGCCCTA GAAGAGTGTG AAAAGGAATG GCAATGGTGT TCACCATCGG CAGTGCCAGG GCAGCACTCA TTCACTTGAT AAATGAATAT TTATTAGCTG GTTGGAGAGC TAGAACCTGG AGAGCTAGAA 45 CCTGGAGAAC TAGAACCTGG AGGGCTAGAA CCTGGAGAGG CTAGAACCAA GAAGGGCTAG AACCTGGAGG GGCTAGAACC TAGAGAAGCT AAAACCTGAG CTAGAAGCTG GAGGACTAGA ACCTGGAGGG CTGGAATCTG AAGGGCTAGA ACCTGGAGGG CTGGAATCTG GAGAGCTAGA ACCTGGAGGG CTAGAACCTG GAGGGCTAGA ACCTAGAAGG GCTAGAACCT GGAGGGCTGG AATCTGGAGA GCTAGAACCT GGAGGGCTAG AACCTGGAGG GCTAGAACCT AGAAGGGCTA GAACCTGGAG GGCTAGAACC TGGCAGGTTA GAACCTAGAA GGGCTAGAAC 50 CTGGAGAGCC AGAACCTGGA GGGCTAGAAC CTGGAAGGGC TAGAACCTGT AGAGCTAGAA CATGGAGAGC TAGAACCCGG CAGGCTAGAA CCTGGCAAGC TAGAACCTGG AGGGAATGAA CCTGGAGGGC TAGAACCTGG AGAATGAGAA AAATACAT GGCAAAGAGC CCATAAATCC TGACCAATCC AACTCTGAAT TTTAAAGCAA AAGCGTGAAA AAAAAGATTC CCTCCTTACC CCCAACCCAC TCTITITCC CACCACCCAC TCTCCTCTGC CTCAGTAAGT ATCTGGAGGA AGAAAACAGG TGAAAGAAGA AGTAAAAACC ATTTAGTATT AGTATTAGAA 55 TGAAGTCAAA CTGTGCCACA CATGGTGAAT GAAAAAAAAA AAAAAGAGGC TGTGTTTTGT CACACAGGGC AGTCATTCAG CACCAGAGCA CGTGATGGTC TGAGACTCTC TTAGGAGCAG AGCTCTGCCG CAATGGCCAT GTGGGGATCC ACACCTGGTC TGAGGGGCAA CTGAGTCTGC GGGAGAAGAG CGGCCCTATG CATGGTGTAG ATGCCCTGAT AAAGAACATC TGTCCTGTGA AAGACTCAAT GAGCTGTTAT GTTGTAAACA GGAAGCATTT CACATCCAAA CGAGAAAATC ATGTAAACAT GTGTCTTTTC TGTAGAGCAT AATAAATGGA TGAGGTTTTT 60 GCAAAAAAAA AAAAAAAAA -3' (FRAG. NO:2275) (SEQ. ID NO:2453) 5'- GAGCTCTTCA ATATTTTAGT GAAAGCTATA GATGAGGCTC CATAGGGGAT AAAGCACAGA CACACCTT CAGAGGGCTT GTGGACTCTG GGCAGCCTGT CCATAGACCT CTGTCCCCAA CTGGCAAGTC AGGAAACTCC AGATTAAGGA GCCCCAATGT GGTTGAACAG CCAGGTGCAC AGATGAGTCA ACCACACAGC CAGGCCAGGG AGGGCCTFCA CTCAAGAGCC TACAGCCAGT TCACAGCCAA GCCAGGGCTA GCGCCAGGCC ACCCATAAAC 65 TGATCTGAGA CTCTGTTTCC CTGTCTCCAT GATGATGGGA TCAGGCTTGA TTGCTGGTTT GTAGGCTTGT TATGAATCAA GTCACAGGGA AGAGGAGCTG ATGGGCTGGG GGGACGTCCT CTGGCCCTCC TGTCTCTTCC WO 00/62736 PCT/USOO/08020 281 CCAGATCCAC TGGGCCCACT CTTATCTGTT CTCTTCTGAA GGAAGGGTTT TAAGGCTTCA AAAAAAAATG TTTTGAAAGT CCCTGCCCTT TCCAGCTCCT ACCGTCTCAG CCCTGGGAGT GTAAAGTGCT GCAGATAGTT AGTAAGTCTT TGAGCAAAAC TGAGAAAGCC AGCCTGAGCC TTGACATGGG AGAAACCTCC GCCATACATC TCCGAAGAAA CGGCCGCGTG TCTCAGGGGA GCGCAAACAC CCGTACCCAG GAAACAGGAC AGCTTCTGCC 5 ACTGTCGCCC TTGGGAGCCG TACGTGGCAT GACAAAGAAA TCCCAGGACT CCGCCTGCCC ACCTGGCCAC CCTCTGTTTA CACCTTCCGC GTAAACGCCC ACTGTTTACA TCCAAAACTC AGACACAAAA TAACCACCTC AAGAAGATAA ATAATGATAA GAAATAAATG TrACGCGAGG CAAATTTATT CACATGGGGC TTCCCAGGCC ACTTTGTGGT CAGCCGGGAG GGACGTTT GCCGTCCCAC GACTCCAACG GGCAGCCGGG CCTACGCAAA CATGGAAATC TTCCAAGAGC CTCCCTGGCC CCCAGGGCTC AGAGGGTGGC AGAGCGGAGA GCGAAGGTGG 10 CCGCAGCCTT CCCGGCCCCA CAGCCAGCCT GGCTCCAGCT GGGCAGGAGT GCAGAGCTCA GCTGGAGGCG AGGGGGAAGT GCCCAGGAGG CTGATGACAT CACTACCCAG CCCTTCAAAG ATGAGCTGTT CCCGCCGCCA CTCCAGCTCT GGCTTCTGGG CTCCGAGGAG GGGTGGGGAC GGTGGTGACG GTGGGGACAT CAGGCTGCCC CGCAGTACCA GGGAGCGACT GAAGTGCCCA TGCCGCTTGC TCCGGAGAAG GTGGGTGCCG GGCAGGGGCT GCTCCAGCCG CCTCACCTCT GCTGGGAGGA CAAACTGTCC CAGCACAGAG GGAGGGAGGG AGGGCAGGCA 15 GCGGGGAGAA GTTTCCCTGT GGTCGTGGGG AGTTGGGAAA AGTTCCCTTC CTTCCGGAGG GAGG-3' (FRAG..NO:2275) (SEQ.ID NO:2452) 5'- GCCCTTCAAA GATGAGCTGT TCCCGCCGCC ACTCCAGCTC TGGCTTCTGG GCTCCGAGGA GGGGTGGGGA CGGTGGTGAC GGTGGGGACA TCAGGCTGCC CCGCAGTACC AGGGAGCGAC TGAAGTGCCC ATGCCGCTTG CTCCGGAGAA GGTGGGTGCC GGGCAGGGGC TGCTCCAGCC GCCTCACCTC TGCTGGGAGG ACAAACTGTC 20 CCAGCACAGA GGGAGGGAGG GAGGGCAGGC AGCGGGGAGA AGTTTCCCTG TGGTCGTGGG GAGTT -3' (FRAG.NO:2275) (SEQ.ID NO:2451) 5'- GCCCTTCAAA GATGAGCTGT TCCCGCCGCC ACTCCAGCTC TGGCTTCTGG GCTCCGAGGA GGGGTGGGGA CGGTGGGGAC ATCAGGCTGC CCCGCAGTAC CAGGGAGCGA CTGAAGTGCC CATGCCGCTT GCTCCGGAGA AGGTGGGTGC CGGGCAGGGG CTGCTCCAGC CGCCTCACCT CTGCTGGGAG GACAAACTGT CCCAGCACAG 25 AGGGAGGGAG GGAGGGCAGG CAGCGGGGAG AAGTTTCCCT GTGGTCGTGG GGAGTT-3' (FRAG.NO:2275) (SEQ. ID NO:2450) 5'- ATGTTCTCTC CCTGGAAGAT ATCAATGTTT CTGTCTGTTC GTGAGGACTC CGTGCCCACC ACGGCCTCTT TCAGCGCCGA CATGCTCAAT GTCACCTTGC AAGGGCCCAC TCTTAACGGG ACCTTTGCCC AGAGCAAATG CCCCCAAGTG GAGTGGCTGG GCTGGCTCAA CACCATCCAG CCCCCCTTCC TCTGGGTGCT GTTCGTGCTG 30 GCCACCCTAG AGAACATCTT TGTCCTCAGC GTCTTCTGCC TGCACAAGAG CAGCTGCACG GTGGCAGAGA TCTACCTGGG GAACCTGGCC GCAGCAGACC TGATCCTGGC CTGCGGGCTG CCCTTCTGGG CCATCACCAT CTCCAACAAC TTCGACTGGC TCTTTGGGGA GACGCTCTGC CGCGTGGTGA ATGCCATTAT CTCCATGAAC CTGTACAGCA GCATCTGTT CCTGATGCTG GTGAGCATCG ACCGCTACCT GGCCCTGGTG AAAACCATGT CCATGGGCCG GATGCGCGGC GTGCGCTGGG CCAAGCTCTA CAGCTTGGTG ATCTGGGGGT GTACGCTGCT 35 CCTGAGCTCA CCCATGCTGG TGTTCCGGAC CATGAAGGAG TACAGCGATG AGGGCCACAA CGTCACCGCT TGTGTCATCA GCTACCCATC CCTCATCTGG GAAGTGTTCA CCAACATGCT CCTGAATGTC GTGGGCTTCC TGCTGCCCCT GAGTGTCATC ACCTTCTGCA CGATGCAGAT CATGCAGGTG CTGCGGAACA ACGAGATGCA GAAGTTCAAG GAGATCCAGA CGGAGAGGAG GGCCACGGTG CTAGTCCTGG TTGTGCTGCT GCTATTCATC ATCTGCTGGC TGCCCTTCCA GATCAGCACC TTCCTGGATA CGCTGCATCG CCTCGGCATC CTCTCCAGCT 40 GCCAGGACGA GCGCATCATC GATGTAATCA CACAGATCGC CTCCTTCATG GCCTACAGCA ACAGCTGCCT CAACCCACTG GTGTACGTGA TCGTGGGCAA GCGCTTCCGA AAGAAGTCTT GGGAGGTGTA CCAGGGAGTG TGCCAGAAAG GGGGCTGCAG GTCAGAACCC ATTCAGATGG AGAACTCCAT GGGCACACTG CGGACCTCCA TCTCCGTGGA ACGCCAGATT CACAAACTGC AGGACTGGGC AGGGAGCAGA CAGTGAGCAA ACGCCAGCAG GGCTGCTGTG AATTTGTGTA AGGATTGAGG GACAGTTGCT T -3' (FRAG. NO:2275) (SEQ. ID NO:2449) 45 5'- ATGTTCTCTC CCTGGAAGAT ATCAATGTTT CTGTCTGTTT GTGAGGACTC CGTGCCCACC ACGGCCTCTT TCAGCGCCGA CATGCTCAAT GTCACCTrGC AAGGGCCCAC TCTTAACGGG ACCTTTGCCC AGAGCAAATG CCCCCAAGTG GAGTGGCTGG GCTGGCTCAA CACCATCCAG CCCCCCTrCC TCTGGGTGCT GTTCGTGCTG GCCACCCTAG AGAACATCTT TGTCCTCAGC GTCTTCTGCC TGCACAAGAG CAGCTGCACG GTGGCAGAGA TCTACCTGGG GAACCTGGCC GCAGCAGACC TGATCCTGGC CTGCGGGCTG CCCTTCTGGG CCATCACCAT 50 CTCCAACAAC TTCGACTGGC TCTTTGGGGA GACGCTCTGC CGCGTGGTGA ATGCCATTAT CTCCATGAAC CTGTACAGCA GCATCTGTTT CCTGATGCTG GTGAGCATCG ACCGCTACCT GGCCCTGGTG AAAACCATGT CCATGGGCCG GATGCGCGGC GTGCGCTGGG CCAAGCTCTA CAGCTTGGTG ATCTGGGGGT GTACGCTGCT CCTGAGCTCA CCCATGCTGG TGTTCCGGAC CATGAAGGAG TACAGCGATG AGGGCCACAA CGTCACCGCT TGTGTCATCA GCTACCCATC CCTCATCTGG GAAGTGTTCA CCAACATGCT CCTGAATGTC GTGGGCTTCC 55 TGCTGCCCCT GAGTGTCATC ACCTTCTGCA CGATGCAGAT CATGCAGGTG CTGCGGAACA ACGAGATGCA GAAGTTCAAG GAGATCCAGA CGGAGAGGAG GGCCACGGTG CTAGTCCTGG TTGTGCTGCT GCTATTCATC ATCTGCTGGC TGCCCTTCCA GATCAGCACC TTCCTGGATA CGCTGCATCG CCTCGGCATC CTCTCCAGCT GCCAGGACGA GCGCATCATC GATGTAATCA CACAGATCGC CTCCTTCATG GCCTACAGCA ACAGCTGCCT CAACCCACTG GTGTACGTGA TCGTGGGCAA GCGCTTCCGA AAGAAGTCTT GGGAGGTGTA CCAGGGAGTG 60 TGCCAGAAAG GGGGCTGCAG GTCAGAACCC ATTCAGATGG AGAACTCCAT GGGCACACTG CGGACCTCCA TCTCCGTGGA ACGCCAGATT CACAAACTGC AGGACTGGGC AGGGAGCAGA CAGTGAGCAA ACGCCAGCAG GGCTGCTGTG AATTTGTGTA AGGATTGAGG GACAGTTGCT T -3' FRAGG. NO:2275) (SEQ. ID NO:2448) 5'- TGATCCTATC ACAACCTGAG AGTAGTT ACTCCATTTA CAGGTGAGGT CATTGTGGTT CAAGGACGTT AAGTAACTTC CCCAGCTCAC ACGGCTTATA AGTAAGGCAG CCAGGATGTG AACCCAGTAG GACTATCTGG 65 CTGCAAAGTC CCCACCCTCC CTCGCCATCT GTATCCTCCA ATCATCTTCA GTGCTTTGCT GATAGAAGGT ACGGAAATAC GATGCCACAG ACTGTCCAGG AAGACAGAAA CTAGGCAGAT GGGCTGGCCA TGGTCTCCAA WO 00/62736 PCT/US00/08020 282 GCCAGACTGG AATCTCCAGG TCTGGAATGA TATCATTTT CTC'TTAAT AAATTAACTC ACCCACCACA CGGCTTTGAG AGGCTCAAAG GTGACCAACT CCCTTGGGAG GGCCCCGGTT GATAAGGAAG GAATGTGAAT CCTCCCATCA CGGAAGCTTC AAGGAGGTCA AGGGTCCAAC ACTTGAGATT GTTAGTGCTG TTGGTGGATA CTGCAGAATA TCCAGTGGAG CCTCAGATGA AGAACATGAG GCCCCGTrA GATCCAAGGA TCAGAGGGGG 5 CTCTGTAAGA CCCAGGGGAG TCAGGTGCAC TGGAGCGCGG GCTGCAGAAA ACAGCCTGAG CTCCACCTCG GCTTCTCCTT GCCCTGGCTG GTTGTCCTTA ACCCCTGTCT CCTTCTGGAC CAGTTTTTGT CCTICCCTTG TGACCTGAGG GGTAACAGCC TCTTTCCAC TTTCTCAG CGCCGACATG CTCAATGTCA CCTTGCAAGG GCCCACTCTT AACGGGACCT TTGCCCAGAG CAAATGCCCC CAAGTGGAGT GGCTGGGCTG GCTCAACACC ATCCAGCCCC CCTrCCTCTG GGTGCTGTTC GTGCTGGCCA CCCTAGAGAA CATCTTTGTC CTCAGCGTCT 10 TCTGCCTGCA CAAGAGCAGC TGCACGGTGG CAGAGATCTA CCrGGGGAAC CTGGCCGCAG CAGACCTGAT CCTGGCCTGC GGGCTGCCCT TCTGGGCCAT CACCATCTCC AACAACTTCG ACTGGCTCTT TGGGGAGACG CTCTGCCGCG TGGTGAATGC CATTATCTCC ATGAACCTGT ACAGCAGCAT CTGTTTCCTG ATGCTGGTGA GCATCGACCG CTACCTGGCC CTGGTGAAAA CCATGTCCAT GGGCCGGATG CGCGGCGTGC GCTGGGCCAA GCTCTACAGC TTGGTGATCT GGGGGTGTAC GCTGCTCCTG AGCTCACCCA TGCTGGTGTT CCGGACCATG 15 AAGGAGTACA GCGATGAGGG CCACAACGTC ACCGCTTGTG TCATCAGCTA CCCATCCCTC ATCTGGGAAG TGTTCACCAA CATGCTCCTG AATGTCGTGG GCTTCCTGCT GCCCCTGAGT GTCATCACCT TCTGCACGAT GCAGATCATG CAGGTGCTGC GGAACAACGA GATGCAGAAG TTCAAGGAGA TCCAGACGGA GAGGAGGGCC ACGGTGCTAG TCCTGGTTGT GCTGCTGCTA TTCATCATCT GCTGGCTGCC CTTCCAGATC AGCACCTTCC TGGATACGCT GCATCGCCTC GGCATCCTCT CCAGCTGCCA GGACGAGCGC ATCATCGATG TAATCACACA 20 GATCGCCTCC TTCATGGCCT ACAGCAACAG CTGCCTCAAC CCACTGGTGT ACGTGATCGT GGGCAAGCGC TTCCGAAAGA AGTCTTGGGA GGTGTACCAG GGAGTGTGCC AGAAAGGGGG CTGCAGGTCA GAACCCATTC AGATGGAGAA CTCCATGGGC ACACTGCGGA CCTCCATCTC CGTGGAACGC CAGATTCACA AACTGCAGGA CTGGGCAGGG AGCAGACAGT GAGCAAACGC CAGCAGGGCT GCTGTGAATT TGTGTAAGGA TTGAGGGACA GTTGCTTC AGCATGGGCC CAGGAATGCC AAGGAGACAT CTATGCACGA CCTTGGGAAA TGAGTGTTGA 25 TGTCTCCGGT AAAACACCGG AGACTAATTC CTGCCCTGCC CAATTTTCGA GGGAGCATGG CTGTGAGGAT GGGGTGAACT CACGCACAGC CAAGGACTCC AAAATCACAA CAGCATTACT GTTCTTATTT GCTGCCACAC CTGAGCCAGC CTGCTCCTTC CCAGGAGTGG AGGAGGCCTG GGGGAGGGAG AGGAGTGACT GAGCTTCCCT CCCGTGTGTT CTCCGTCCCT GCCCCAGCAA GACAACTTAG ATCTCCAGGA GAACTGCCAT CCACGTTTGG TGCAATGGCT GAGTGCACAA GTGAGTTGTT GCCCTGGGTT TCTTTAATCT ATCAGCTAGA ACYTGAAGG 30 ACAATTTCTT GCATTAATAA AGGTTAAGCC CTGAGGGGTC CCTTGATAAC AACCTGGAGA CCAGGATTT ATGGCTCCCC TCACTGATGG ACAAGGAGGT CTGTGCCAAA GAAGAATCAA TAAGCACATA TGAGCACTTC TGTATATCAG TATTGAGCAC TGTAGGCA -3' (FRAG. NO:2275) (SEQ. ID NO:2447) 5'- CTGCAGAAAA CAGCCTGAGC TCCACCTCGG CTTCTCCTTG CCCTGGCTGG TTGTCCTTAA CCCCTGTCTC CTTCTGGACC AGTTTGTC CTTCCCTTGT GACCCTGAGG GGTAACAGCC TCTTTTCCAC TTTCTTTCAG 35 CGCCGACATG CTCAATGTCA CCTTGCAAGG GCCCACTCTT AACGGGACCT TTGCCCAGAG CAAATGCCCC CAAGTGGAGT GGCTGGGCTG GCTCAACACC ATCCAGCCCC CCT7CCTCTG GGTGCTGTTC GTGCTGGCCA CCCTAGAGAA CATCTTTGTC CTCAGCGTCT TCTGCCTGCA CAAGAGCAGC TGCACGGTGG CAGAGATCTA CCTGGGGAAC CTGGCCGCAG CAGACCTGAT CCTGGCCTGC GGGCTGCCCT TCTGGGCCAT CACCATCTCC AACAACTTCG ACTGGCTCTT TGGGGAGACG CTCTGCCGCG TGGTGAATGC CATTATCTCC ATGAACCTGT 40 ACAGCAGCAT CTGTTTCCTG ATGCTGGTGA GCATCGACCG CTACCTGGCC CTGGTGAAAA CCATGTCCAT GGGCCGGATG CGCGGCGTGC GCTGGGCCAA GCTCTACAGC TTGGTGATCT GGGGGTGTAC GCTGCTCCTG AGCTCACCCA TGCTGGTGTT CCGGACCATG AAGGAGTACA GCGATGAGGG CCACAACGTC ACCGCTTGTG TCATCAGCTA CCCATCCCTC ATCTGGGAAG TGTTCACCAA CATGCTCCTG AATGTCGTGG GCTTCCTGCT GCCCCTGAGT GTCATCACCT TCTGCACGAT GCAGATCATG CAGGTGCTGC GGAACAACGA GATGCAGAAG 45 TTCAAGGAGA TCCAGACGGA GAGGAGGGCC ACGGTGCTAG TCCTGGTTGT GCTGCTGCTA TTCATCATCT GCTGGCTGCC CTTCCAGATC AGCACCTTCC TGGATACGCT GCATCGCCTC GGCATCCTCT CCAGCTGCCA GGACGAGCGC ATCATCGATG TAATCACACA GATCGCCTCC TTCATGGCCT ACAGCAACAG CTGCCTCAAC CCACTGGTGT ACGTGATCGT GGGCAAGCGC TTCCGAAAGA AGTCTTGGGA GGTGTACCAG GGAGTGTGCC AGAAAGGGGG CTGCAGGTCA GAACCCATTC AGATGGAGAA CTCCATGGGC ACACTGCGGA CCTCCATCTC 50 CGTGGAACGC CAGATTCACA AACTGCAGGA CTGGGCAGGG AGCAGACAGT GAGCAAACGC CAGCAGGGCT GCTGTGAATT TGTGTAAGGA TTGAGGGACA GTTGCITITC AGCATGGGCC CAGGAATGCC AAGGAGACAT CTATGCACGA CCTTGGGAAA TGAGTFGATG TCTCCGGTAA AACACCGGAG ACTAATTCCT GNCCTGCCCA ATTGCAGG GAGCATGGCT GTGAGGATGG GGTGAACTCA CGCACAGCCA AGGACTCCAA AATCACAACA GCATTACTGT TCTTATTTGC TGCCACACCT GAGCCAGCCT GCTCCTTCCC AGGAGTGGAG GAGGCCTGGG 55 GGCAGGGAGA GGAGTGACTG AGCTTCCCTC CCGTGTGTTC TCCGTCCCTG CCCCAGCAAG ACAACTTAGA TCTCCAGGAG AACTGCCATC CAGCTTGGT GCAATGGCTG AGTGCACAAG TGAGTTGTTG CCCTGGGTT CTTTAATCTA TTCAGCTAGA ACTTTGAAGG ACAATTTCTT GCATTAATAA AGGTTAAGCC CTGAGGGGTC CCTGATAACA ACCTGGAGAC CAGGATTA TGGCTCCCCT CACTGATGGA CAAGGGAGGT CTGTGCCAAA GAAGAATCCA ATAAGCACAT ATTGAGCACT TGCTGTATAT GCAGTATTGA GCACTGTAGG CAAGAGGGAA 60 GAAAGAGAAG GAGCCATCTC CATCTTGAAG GAACTCAAAG ACTCAAGTGG GAACGACTGG CACTGCCACC ACCAGAAAGC TGT7CGACGA GACGGTCGAG CAGGGTGCTG TGGGTGATAT GGACAGCAGA AGGGGGAGAC CAAGGTTCCA GCTCAACCAA TAACTATTGC ACAACCACCT GTCCCTGCCT CAGTTCCCTC TTCTGTAACA TGAAGTCGTT GTGAGGGTTA AAGGCAGTAA CAGGTATAAA GTACTTAGAA AAGCAAAGGG TGCTACGTAC ATGTGAGGCA TCATTACGCA GACGTAACTG GGATATGTTT ACTATAAGGA AAAGACACTG AGGTCTAGA -3' 65 (FRAG. NO:2275) (SEQ. ID NO:2446) 5'- AAATGATAGA CCGTCAATAA TGTTAAAT GCTTTTTAAA ATGAATGCTT TAAGCCGGGT GCAGTGCCTC WO 00/62736 PCT/USOO/08020 283 ACATCTGTAA TCCCAGCACT TTGGAGCCGA GCGGGTGGAT TGTGTGAGGT CAGGAGTTCG AGACCAACCT GGCCAACATG GCAAAACCTC ACTCTCTACC AAAAATACAA AAATTAGCCA GGCATGGTGG CAGGCACCTG TGATCCCAGC TACTCAGGAG GCTGAGACAG GAGAATCGCT TGAACCCGGG AGGCAAGGTT GCAGTGAGCC AAGATTACGC CATTGTACTC CAGCCTGGGT GACAGAGAGA GACTCCGTCT CAAAAAAAAA AAAAAAAAAA 5 AAAAAATTAC GCTTCAAACA CATGATCTCT CACCACTGTT GAATTTTCTT TCTATGAGCC CAGGAGGGCC TCTCAGAGAG GAAAGCTCCT AGGTCTTCCT TTCCCTCTGC AAACTCCCTG CCTTGAAGGT TCAGAAGGAC TGTGCGTGCT CGTrGCATCC TTTGCAAGTG TCCAAACCCT GATCCCAGCT GTGCTTAGGG GTTCCTGCAA ACCTTTCCA GGTGTTAATT ACCTCCCACT TCATTTCCTG TTTACCAACT CAGCTTTG TTTTAGTGTG TTTGAATTCC CTGAACTGAC CGTTGTCTGA TCTCCACCTC CCAACTGAAT TAGGGGAGCT GGGCTTCTGG 10 AAACCCAGGT GCCGGGTGTT GCAGAGTGGC TGAAAGCTGG GATGTGGCAG ATCCGTGGCT ACATTCATGC ACACACACAC ACCCACATAC CCACACATGC ACACACACAC ACACACCCGC ACTCACACAC TTGGACATGC ATAGACCACA GC'TCCACA CCCTTCCTAG ACAGGGGTCA CTTGGTATCC TGGAGAGAGT GTGAAGTCCT GGAATGGAAA GAGGGGGGAT TAAGCCCCAC CTCTAGCCAT GGGACTGAGA CAAGTCACCA CCAACCCATC TGCGCCTTGT TTACCTCCTC TGTGAGGCAA GCACAGAGCC CATGCCTGCC CCCCTGGATG GGAGTGATGT 15 GAAACTTGAA GGGCGGTCAG AGCAAGGGTC GGGAATGGAA GGCCCTTGGG AAAAAAGGCC CTTTCAACTA GGGGCACAGA GGAGGCCCTG GGCTGAGAAC TTGACAGCAC CTTGTAATTG GTAAGCCAAG CCCGAAGGGA CTGGAAATAC TCAGATGTGT CTGTCTCCCT TATTAGGTTC AAAGTCCCTC AAGACCCTGT CTCCATCACA GTGCTCCAGT CCAGACCCCT CCTCTGAGCT CCAGACCCTG CTGGACCCAA CCAGCCCTAT GGGGTCGCAT CCCCACCTGC CTGGAATTCT CCAAAGAACC TCCCCTTTAA CAGTTCCAGC CTTTAACAGT TCCAGTCTAA 20 ACACATGACC TTTCTCCTCT AAATCAGCCC CCCATCTCTG CCTTTGCAGG AGATGGAAGC CATGACACCT GCCTCGCCCC TGTCCTCACC CCATCCATGT CCAATCAAGC ACTAGGCATG TCAGGTTTAC CCTCTAAACT CCTCTGGAAT CCAGTCTCTC AGTCTCCATC ATCCCAGGTC GAAGCTAATG GGCTAACTGG TCCTTGCTTC CACTCTACCC CCACTGCAGT CCTGACTTCC TGAGCAGCAG CCAGGGCCTA ATCGATATTC ACACCAAGCG CCAACCTGAC TGAGATATCC TCCTGCACCA TCATCCCTCC ACCCTGTTTA GTTCTGCTCA CCCTCAGTGT 25 TCTCATCAAT AATCCACTCC CCTCACAGGC GCGTTrGGGA CCCCATGTTC TATGCTCTCA CAGGACCTTT TGCTTGATTT TTCACTGTAC TTAGGTCAGT TTGCAGTTAT TAAGTGACTG AGCAATGTCT GGCTTCTCCA GTAGACTGTC AGCTCCTAGC CATTGTATAC CTAGCACCGC TGTGTGGGAG CACGTGACAA ACGTCCAGTG AGTCAGGGAC TCAGCAGTCT CCATTCTCC GCCCTGCTGG AGAATGCGTG TATTTGGCAA TCCCCAGCCC CTGTGCCATC TAACCATCTT TTCTTCTCTG TTCAGCCCAG GTGTGGCCTC ACTCACATCC CACTCTGAGT 30 CCAAATGTTC TCTCCCTGGA AGATATCAAT GTTTCTGTCT GTTCGTGAGG ACTCCGTGCC CACCACGGCC TCTTTCAGGT GAGTCAAAGG GATTCCTCAG TTCACTAGTT AGGGGAGGTG GGCAGACACC CTGGAGAACT CCCTGGAAAG CTCAACTCTC ATGCCCCGGA CAACAGTTGA AGGAACCATG GTGATGTTAA GCCCAAAGAC AAAACCTCTC AGGTGTCCAA GTCCCTGTTG GAATCTTGGG AGCAGAGGGA ATGTTCTGTG GTCTAGAGGA AGAGGGGCTC AGGGAGGAGA AGGGCACATT CCTGGTTGTT ATATGTTrCT ATCTATCCCA GATGAACTTG 35 GAAGTGAAGG GAAGAGAGTT AAACATTAAA GTAAATACCC AGTGGATCAG ACAGCAATGT GCCAGATTGC CTTGGAAACA AAATATCTCC AACACATGGC TGACATTTGG TGGGAGATCA GAACACCCTA AAGAGAGAAT TTAAGGGGAG GGGGAGGAGG ACCTGAGCCA GAGTAGAAGC AGAGGATAGG GAGATCTGTT CTTGGGGACA GCATTTGCAA GAAACAAGGC TGAGGGGTCC ACTCCAACCT CTCCACCCTG CTGCAGGTGC TGCCTATGAT GAAGATGAGC AGATGGCCAT CTCAGCTGGG GCCACAGTGC ACTGGACCTA TAGTTTCCAA TTCCGCACTC 40 AGCAGGCATC TTTCTGATGA TCCGATGGCT TCTCAGAGCC AGGGATGGGC CAGGATCCAT CCCCTTGGCT ACTGTCTTGC TGAGAAATTT ATAAGCAGCA TCTGGTGCTA TACTTTGGTC TCTAGTGAGT TAGCTCATGA AAGATGATAG ACTCTCCAAG CCAGGGGTAT GCAGGAAATG GGTTTCTGT AGCTACAGAA ATGGGGTTGA GGGTTGGACC AAGGGACTAC CCAGGGGAAG TCTTACCTTC AGAGGACTCT GGAAAGGAGG CTGCAAGTTT TCATGGGTCA AGAATTCAGA GCCCAGTAGA GACAGCTTAT CTCTGTTCCA AGATGTCTGG GGCCTTGGTT 45 GGAAGATTCA AAGGCTAGGA AACCAGGAGC CACCAAAAGC GTAACTGGGG CCAGAGGATC CACTTTCAAG GTGGCAAGTT GGTTCCCCCC ATGTGGCTGC TTGAGTATCC TCACATGGCG GCTCACATCC TTCCAAGTAA GCAATGCAAA AGGCCAAGAA AGATGCTGCA AAGATGTTAT GACCTAGCCT CAGAAATCAC ACACCATCCC TGCCACCATT AGTAAGAAGT CCAGCCCACG TCCAGGAGAA GAGGAAGCAG ATrCCTCCTT TTGAAATGAA GAATATCAAG TAATTCGGGG GGCATATGAA AGCCACCACA CACCACAGGG ATCTTTTTAG AGCATACTTC 50 TTATACCATC ACTGTAGTTC CTTAAGACTC AGGGGCAAAG CCTCACTTCC TTAGCACCCA GTGAAGACCA CGCTTACTCC CTCACTCAAC CTCTTGCTAC TTCCCACCTC TCCTGTCCAA CATCTAGTGT CACTTTCCAG AACATACCAA CAGCTTCCCC AGTTCTGTGC CTCTGCTCAG GCTGTTCCCC CTGCCTGGTC CACTTGTCCT CCTTCTTGTC CGGTCAAAAT GCTTCTTATC CTTCAAGACC CAGCTCTAGA GTCACCTCCA ACCCCTTACC CACCAGCCCC CTCTCCAAGT CTGTGTCCCA CAACCCCCCT GCTCCCTCCA GGGCACCCTC CACCCTCTGG 55 GCCACAGTTG TCAGGAGTCA GGCAGGGCAG GGGCCGGGTG GTGTCTTCTT TGTGTTCTTG CACTCAGGGC AGAGCTCAGC ACAGAGCAGA CGCTCAAAAA ACATTTAAAG GATAGAAGCA TTGATTGTG GGTCCCCCAG TCTGGCTCCA GGATGCCAGC CAGCTGCTCC TAGAAGCAAA CGGACTTT-TC CTGGGAAATC CCAGAGGTGA TGATCAGTAA TCTCTCCCGT GACTCGTAGT TCAGCTCTTC CTCCATGAGC CTGACTATCA GTGGACCTTC CAGAAAGAGC CCCTTTCCT TCTCTCACCC ACAGCACAGG GCACTGGGAA AATGCCCAAT GAGTCCTGCC 60 TCTGGGTTGT GCTTTGGACT TTTCAGTGTG TCTCGCATCC ACTCTTCAAC TTGAATGTTG CAACAGCCAT GAAAAAAGAA ATGCAAAGCG ATTCAGGATG AGAGCAATAC CCTACTCCAA AGAAGGCAAC ATAGAAGCTC AGAGAGATCA AGCAATTTGC CCAAGACCAC ACAGCTAGGA GTGGAACTCA TGGCTGTCCA AGCCCCATGC CTCTGCTGAA GGTAGAGATG AATTACAGCA ACAAGTCTAG AAAGGTGCCT GCCCTATGGT CTGTGAGTCT TGCCTAAGAA TGAAAGAGGA GCCAGTGGGT TAAAGATGAG GTCACCAACA ACGGTGGTGT TGGAGTTTAC 65 CACTGATAAT AAGGGTGCAA AATGTAAATT ACTAATGTTT ATTGAGCCTA GTGCAGTGCG TGGGGCATTT TGCACATTGT CTCTGATCCC TATGACAACC CTGAGAGGTA GTGGTTAA CTGCCATGTT ACAGGTGAGG WO 00/62736 PCT/US00/08020 284 TCATTGTGGT TCAAGGACGT TAAGTAACTT CCCCAGCGTG ACACGGCTrA TAAGTAAGGC AGCCAGGATG TGAACCCAGT AGGACTATCT GGCTGCAAAG TCCCCACCCC CCTCGCCATC TGTATCCTCC AATCACTTCA GTGCTTTGCT GCATAGAAGG TAACGGAAAT CACGATGCCA CAGACTGTCC AGGAAGACAG AAACTAGGCA GATGGGCTGG CCATGGTCTC CAAGCCAGAC TGGAATCTCC AGGTCTGGAA TGATATCATr TTTCTCTTTT 5 AATAAATTAA CTCACCCACC ACACGGCTTT GAGAGGCTCA AAGTTGACCA ACTCCCTTGG GAGGGCCCCG GTTGATAAGG AAGGAACGTG AATCCTCCCA TCACGGAAGC TTCAAGGAGG TCAAGGGTCC AACACTTGAG ATTGTTAGTG CTGTTGGTGG ATACTGGCCA AGGAAATATC CCAGTGGAGC CTCGAGATGA AGAACATGAG GCCCCCGTTT AGAACCAAGG ATCAGAGGGG GCTCTGTAAG ACCCAGGGGA GTCAGGTGCA CTGGAGCGCG GGCATGCAGA AAACAGCCTG AGCTCCACCT CGGCTTCTCC TrGTCCTGGC TGGTTGTCCT TAACCCCTGT 10 CTCCTTCTGG ACCAGTTTTT GTCCTTCCCT TGTGACCGCT GAGGGGTAAC AGCCTCTTTC CACTTTCTTT CAGCGCCGAC ATGCTCAATG TCACCTTGCA AGGGCCCACT CTTAACGGGA CCTTTGCCCA GAGCAAATGC CCCCAAGTGG AGTGGCTGGG CTGGCTCAAC ACCATCCAGC CCCCCTTCCT CTGGGTGCTG TTCGTGCTGG CCACCCTAGA GAACATCTTT GTCCTCAGCG TCTTCTGCCT GCACAAGAGC AGCTGCACGG TGGCAGAGAT CTACCTGGGG AACCTGGCCG CAGCAGACCT GATCCTGGCC TGCGGGCTGC CCTTCTGGGC CATCACCATC 15 TCCAACAACT TCGACTGGCT CTTTGGGGAG ACGCTCTGCC GCGTGGTGAA TGCCATTATC TCCATGAACC TGTACAGCAG CATCTGTTTC CTGATGCTGG TGAGCATCGA CCGCTACCTG GCCCTGGTGA AAACCATGTC CATGGGCCGG ATGCGCGGCG TGCGCTGGGC CAAGCTCTAC AGCTTGGTGA TCTGGGGGTG TACGCTGCTC CTGAGCTCAC CCATGCTGGT GTTCCGGACC ATGAAGGAGT ACAGCGATGA GGGCCACAAC GTCACCGCTT GTGTCATCAG CTACCCATCC CTCATCTGGG AAGTGTTCAC CAACATGCTC CTGAATGTCG TGGGCTTCCT 20 GCTGCCCCTG AGTGTCATCA CCTTCTGCAC GATGCAGATC ATGCAGGTGC TGCGGAACAA CGAGATGCAG AAGTrCAAGG AGATCCAGAC GGAGAGGAGG GCCACGGTGC TAGTCCTGGT TGTGCTGCTG CTATTCATCA TCTGCTGGCT GCCCTTCCAG ATCAGCACCT TCCTGGATAC GCTGCATCGC CTCGGCATCC TCTCCAGCTG CCAGGACGAG CGCATCATCG ATGTAATCAC ACAGATCGCC TCCTTCATGG CCTACAGCAA CAGCTGCCTC AACCCACTGG TGTACGTGAT CGTGGGCAAG CGCTTCCGAA AGAAGTCTTG GGAGGTGTAC CAGGGAGTGT 25 GCCAGAAAGG GGGCTGCAGG TCAGAACCCA TTCAGATGGA GAACTCCATG GGCACACTGC GGACCTCCAT CTCCGTGGAA CGCCAGATTC ACAAACTGCA GGACTGGGCA GGGAGCAGAC AGTGAGCAAA CGCCAGCAGG GCTGCTGTGA ATTTGTGTAA GGATTGAGGG ACAGTTGCTT TTCAGCATGG GCCCAGGAAT GCCAAGGAGA CATCTATGCA CGACCTTGGG AAATGAGTTG ATGTCTCCGG TAAAACACCG GAGACTAATT CCTGCCCTGC CCAATTTTGC AGGGAGCATG GCTGTGAGGA TGGGGTGAAC TCACGCACAG CCAAGGACTC CAAAATCACA 30 ACAGCATTAC TGTTCTTATT TGCTGCCACA CCTGAGCCAG CCTGCTCCTr CCCAGGAGTG GAGGAGGCCT GGGGGCAGGG AGAGGAGTGA CTGAGCTTCC CTCCCGTGTG TTCTCCGTCC CTGCCCCAGC AAGACAACTT AGATCTCCAG GAGAACTGCC ATCCAGCTTT GGTGCAATGG CTGAGTGCAC AAGTGAGTTG TTGCCCTGGG TTTCTTTAAT CTATTCAGCT AGAACTTTGA AGGACAATTT CTTGCATTAA TAAAGGTTAA GCCCTGAGGG GTCCCTGATA ACAACCTGGA GACCAGGATT TTATGGCTCC CCTCACTGAT GGACAAGGAG GTCTGTGCCA 35 AAGAAGAATC CAATAAGCAC ATATTGAGCA CTTGCTGTAT ATGCAGTATT GAGCACTGTA GGCAAGAGGG AAGAAAGAGA AGGAGCCATC TCCATCTTGA AGGAACTCAA AGACTCAAGT GGGAACGACT GGGCACTGCC ACCACCAGAA AGCTGTTCGA TGAGACGGTC GAGCAGGGTG CTGTGGGTGA TATGGACAGC AGAAGGGGGA GCCAGGTTCC AGCTCACCAA TACTATTGCA CACCACCTGT CCTGCCTC-3' (FRAG.NO:2275) (SEQ. D NO:2445) 5'-CAGATTCACA AACTGCAGGA CTGGGCAGGG AGCAGACAGT GAGCAAACGC CAGCAGGGCT GCTGTGAATT 40 TGTGTAAGGA TTGAGGGACA GTTGCTTC AGCATGGGCC CAGGAATGCC AAGGAGACAT CTATGCACGA CCTTGGGAAA TGAGTTGATG TCTCCGGTAA AACACCGGAG ACTAATTCCT GCCCTGCCCA ATTTTGCAGG GAGCATGGCT GTGAGGATGG GGTGAACTCA CGCACAGCCA AGGACTCCAA AATCACAACA GCATTACTGT TCTTATTTGC TGCCACACCT GAGCCAGCCT GCTCCTTCCC AGGAGTGGAG GAGGCCTGGG GGGAGGGAGA GGAGTGACTG AGCTTCCCTC CCGTGTGTTC TCCGTCCCTG CCCCAGCAAG ACAACTTAGA TCTCCAGGAG 45 AACTGCCATC CAGCTTTGGT GCAATGGCTG AGTGCACAAG TGAGTTGTrG CCCTGGGT CTTTAATCTA TTCAGCTAGA ACTTTGAAGG ACAATTTCTT GCATTAATAA AGGTTAAGCC CTGAGGGGTC CCTGATAACA ACCTGGAGAC CAGGATTA TGGCTCCCCT CACTGATGGA CAAGGAGGTC TGTGCCAAAG AAGAATCCAA TAAGCACATA TTGAGCACTT GCTGTATATG CAGTATTGAG CACTGTAGGC AAGACCCAAG AAAGAGAAGG AGCCATCTCC ATCTTGAAGG AACTCAAAGA CTCAAGTGGG AACGACTGGG CACTGCCACC ACCAGAAAGC 50 TGTTCGACGA GACGGTCGAG CAGGGTGCTG TGGGTGATAT GGACAGCAGA AGGGGGAGAC CAAGGTTCCA GCTCAACCAA TAACTATTGC ACAACCACCT GTCCCTGCCT CAGTTCCCTT TTATGTAACA TGAAGTCGTT GTGAGGGTTA AAGGCAGTAA CAGGTATAAA GTACTTAGAA AAGCAAAGGG TGCTACGTAC ATGTGAGGCA TCATTACGCA GACGTAACTG GGATATGTTT ACTATAAGGA AAAGACACTG AGGTCTAGAA ATAGCTCCGT GGAGCAGAAT CAGTATTGGG AGCCGGTGGC GGTGTGAAGC ACCAGTGTCT GGCACACAGT AGGTGCTCAT 55 TGGCTCCCTT CCACCTGTCA TTCCCACCAC CCTGAGGCCC CAACCGCCAC ACACACAGGA GCATTTGGAG AGAAGGCCAT GTCTTCAAAG TCTGATTTGT GATGAGGCAG AGGAAGATAT TTCTAATCGG TCTTGCCCAG AGGATCACAG TGCTGAGACC CCCCACCACC AGCCGGTACC TGGGAAGGGG GAGAGTGCAG GCCTGCTCAG GGACTGTTCC TGTCTCAGCA ACCAAGGGAT TGTTCCTGTC AATCAATGGT TTATTGGAAG GTGGCCCAGT ATGAGCCCTA GAAGAGTGTG AAAAGGAATG GCAATGGTGT TCACCATCGG CAGTGCCAGG GCAGCACTCA 60 TTCACTTGAT AAATGAATAT TTATTAGCTG GTTGGAGAGC TAGAACCTGG AGAGCTAGAA CCTGGAGAAC TAGAACCTGG AGGGCTAGAA CCTGGAGAGG CTAGAACCAA GAAGGGCTAG AACCTGGAGG GGCTAGAACC TAGAGAAGCT AAAACCTGAG CTAGAAGCTG GAGGACTAGA ACCTGGAGGG CTGGAATCTG AAGGGCTAGA ACCTGGAGGG CTGGAATCTG GAGAGCTAGA ACCTGGAGGG CTAGAACCTG GAGGGCTAGA ACCTAGAAGG GCTAGAACCT GGAGGGCTGG AATCTGGAGA GCTAGAACCT GGAGGGCTAG AACCTGGAGG GCTAGAACCT 65 AGAAGGGCTA GAACCTGGAG GGCTAGAACC TGGCAGGTTA GAACCTAGAA GGGCTAGAAC CTGGAGAGCC AGAACCTGGA GGGCTAGAAC CTGGAAGGGC TAGAACCTGT AGAGCTAGAA CATGGAGAGC TAGAACCCGG WO 00/62736 PCT/USOO/08020 285 CAGGCTAGAA CCTGGCAAGC TAGAACCTGG AGGGAATGAA CCTGGAGGGC TAGAACCTGG AGAATGAGAA AAATTTACAT GGCAAAGAGC CCATAAATCC TGACCAATCC AACTCTGAAT TTTAAAGCAA AAGCGTGAAA AAAAAGATTC CCTCCTTACC CCCAACCCAC TCTTTCC CACCACCCAC TCTCCTCTGC CTCAGTAAGT ATCTGGAGGA AGAAAACAGG TGAAAGAAGA AGTAAAAACC ATTrAGTATT AGTATTAGAA TGAAGTCAAA 5 CTGTGCCACA CATGGTGAAT GAAAAAAAAA AAAAAGAGGC TGTGTTTTGT CACACAGGGC AGTCATTCAG CACCAGAGCA CGTGATGGTC TGAGACTCTC TTAGGAGCAG AGCTCTGCCG CAATGGCCAT GTGGGGATCC ACACCTGGTC TGAGGGGCAA CTGAGTCTGC GGGAGAAGAG CGGCCCTATG CATGGTGTAG ATGCCCTGAT AAAGAACATC TGTCCTGTGA AAGACTCAAT GAGCTGTTAT GTTGTAAACA GGAAGCATrT CACATCCAAA CGAGAAAATC ATGTAAACAT GTGTCTTTTC TGTAGAGCAT AATAAATGGA TGAGGTTTTT GCAAAAAAAA 10 AAAAAAAAA-3' (FRAG. NO:2275) (SEQ. ID NO:2444) 5'- GAGCTCTTCA ATATTTTAGT GAAAGCTATA GATGAGGCTC CATAGGGGAT AAAGCACAGA CACACCTT CAGAGGGCTT GTGGACTCTG GGCAGCCTGT CCATAGACCT CTGTCCCCAA CTGGCAAGTC AGGAAACTCC AGATTAAGGA GCCCCAATGT GGTTGAACAG CCAGGTGCAC AGATGAGTCA ACCACACAGC CAGGCCAGGG AGGGCCTTCA CTCAAGAGCC TACAGCCAGT TCACAGCCAA GCCAGGGCTA GCGCCAGGCC ACCCATAAAC 15 TGATCTGAGA CTCTGTTCC CTGTCTCCAT GATGATGGGA TCAGGCTrGA TTGCTGGTTT GTAGGCTTGT TATGAATCAA GTCACAGGGA AGAGGAGCTG ATGGGCTGGG GGGACGTCCT CTGGCCCTCC TGTCTCTTCC CCAGATCCAC TGGGCCCACT CTTATCTGTT CTCTTCTGAA GGAAGGG'TT TAAGGCTTCA AAAAAAAATG TTTTGAAAGT CCCTGCCCTT TCCAGCTCCT ACCGTCTCAG CCCTGGGAGT GTAAAGTGCT GCAGATAGTT AGTAAGTCTT TGAGCAAAAC TGAGAAAGCC AGCCTGAGCC TTGACATGGG AGAAACCTCC GCCATACATC 20 TCCGAAGAAA CGGCCGCGTG TCTCAGGGGA GCGCAAACAC CCGTACCCAG GAAACAGGAC AGCTTCTGCC ACTGTCGCCC TTGGGAGCCG TACGTGGCAT GACAAAGAAA TCCCAGGACT CCGCCTGCCC ACCTGGCCAC CCTCTGTTTA CACCTTCCGC GTAAACGCCC ACTGTTTACA TCCAAAACTC AGACACAAAA TAACCACCTC AAGAAGATAA ATAATGATAA GAAATAAATG TTACGCGAGG CAAATTTATT CACATGGGGC TTCCCAGGCC ACTTTGTGGT CAGCCGGGAG GGACGTTT GCCGTCCCAC GACTCCAACG GGCAGCCGGG CCTACGCAAA 25 CATGGAAATC TTCCAAGAGC CTCCCTGGCC CCCAGGGCTC AGAGGGTGGC AGAGCGGAGA GCGAAGGTGG CCGCAGCCTT CCCGGCCCCA CAGCCAGCCT GGCTCCAGCT GGGCAGGAGT GCAGAGCTCA GCTGGAGGCG AGGGGGAAGT GCCCAGGAGG CTGATGACAT CACTACCCAG CCCTTCAAAG ATGAGCTGTT CCCGCCGCCA CTCCAGCTCT GGCTTCTGGG CTCCGAGGAG GGGTGGGGAC GGTGGTGACG GTGGGGACAT CAGGCTGCCC CGCAGTACCA GGGAGCGACT GAAGTGCCCA TGCCGCTrGC TCCGGAGAAG GTGGGTGCCG GGCAGGGGCT 30 GCTCCAGCCG CCTCACCTCT GCTGGGAGGA CAAACTGTCC CAGCACAGAG GGAGGGAGGG AGGGCAGGCA GCGGGGAGAA GTCCCTGT GGTCGTGGGG AGTTGGGAAA AGTTCCCTTC CTTCCGGAGG GAGG-3' (FRAG.NO:2275) (SEQ. ID NO:2443) 5'- GCCCTTCAAA GATGAGCTGT TCCCGCCGCC ACTCCAGCTC TGGCTTCTGG GCTCCGAGGA GGGGTGGGGA CGGTGGTGAC GGTGGGGACA TCAGGCTGCC CCGCAGTACC AGGGAGCGAC TGAAGTGCCC ATGCCGCTTG 35 CTCCGGAGAA GGTGGGTGCC GGGCAGGGGC TGCTCCAGCC GCCTCACCTC TGCTGGGAGG ACAAACTGTC CCAGCACAGA GGGAGGGAGG GAGGGCAGGC AGCGGGGAGA AGTTTCCCTG TGGTCGTGGG GAGTT -3 (FRAG. NO:2275) (SEQ. ID NO:2442) 5'- AAATGATAGA CCGTCAATAA TTTGTTAAAT GCTTTAAA ATGAATGCTT TAAGCCGGGT GCAGTGCCTC ACATCTGTAA TCCCAGCACT TTrGGAGCCGA GCGGGTGGAT TGTGTGAGGT CAGGAGTTCG AGACCAACCT 40 GGCCAACATG GCAAAACCTC ACTCTCTACC AAAAATACAA AAATTAGCCA GGCATGGTGG CAGGCACCTG TGATCCCAGC TACTCAGGAG GCTGAGACAG GAGAATCGCT TGAACCCGGG AGGCAAGGTT GCAGTGAGCC AAGATTACGC CATTGTACTC CAGCCTGGGT GACAGAGAGA GACTCCGTCT CAAAAAAAAA AAAAAAAAAA AAAAAATTAC GCTTCAAACA CATGATCTCT CACCACTGTT GAATTTTCTT TCTATGAGCC CAGGAGGGCC TCTCAGAGAG GAAAGCTCCT AGGTCTTCCT TTCCCTCTGC AAACTCCCTG CCTTGAAGGT TCAGAAGGAC 45 TGTGCGTGCT CGTTGCATCC TTTGCAAGTG TCCAAACCCT GATCCCAGCT GTGCTTAGGG GTTCCTGCAA ACCTTTTCCA GGTGTTAATT ACCTCCCACT TCATTTCCTG TTTACCAACT CAGCTTTTG TTTTAGTGTG TTTGAATTCC CTGAACTGAC CGTTGTCTGA TCTCCACCTC CCAACTGAAT TAGGGGAGCT GGGCTTCTGG AAACCCAGGT GCCGGGTGTT GCAGAGTGGC TGAAAGCTGG GATGTGGCAG ATCCGTGGCT ACATICATGC ACACACACAC ACCCACATAC CCACACATGC ACACACACAC ACACACCCGC ACTCACACAC TTGGACATGC 50 ATAGACCACA GCTTTCCACA CCCTTCCTAG ACAGGGGTCA CTTGGTATCC TGGAGAGAGT GTGAAGTCCT GGAATGGAAA GAGGGGGGAT TAAGCCCCAC CTCTAGCCAT GGGACTGAGA CAAGTCACCA CCAACCCATC TGCGCCTTGT TTACCTCCTC TGTGAGGCAA GCACAGAGCC CATGCCTGCC CCCCTGGATG GGAGTGATGT GAAACTTGAA GGGCGGTCAG AGCAAGGGTC GGGAATGGAA GGCCCTTGGG AAAAAAGGCC CTTTCAACTA GGGGCACAGA GGAGGCCCTG GGCTGAGAAC TTGACAGCAC CTTGTAATTG GTAAGCCAAG CCCGAAGGGA 55 CTGGAAATAC TCAGATGTGT CTGTCTCCCT TATTAGGTTC AAAGTCCCTC AAGACCCTGT CTCCATCACA GTGCTCCAGT CCAGACCCCT CCTCTGAGCT CCAGACCCTG CTGGACCCAA CCAGCCCTAT GGGGTCGCAT CCCCACCTGC CTGGAATTCT CCAAAGAACC TCCCCTAA CAGTTCCAGC CTTTAACAGT TCCAGTCTAA ACACATGACC TTTCTCCTCT AAATCAGCCC CCCATCTCTG CCTTTGCAGG AGATGGAAGC CATGACACCT GCCTCGCCCC TGTCCTCACC CCATCCATGT CCAATCAAGC ACTAGGCATG TCAGGTTAC CCTCTAAACT 60 CCTCTGGAAT CCAGTCTCTC AGTCTCCATC ATCCCAGGTC GAAGCTAATG GGCTAACTGG TCCTTGCTTC CACTCTACCC CCACTGCAGT CCTGACTTCC TGAGCAGCAG CCAGGGCCTA ATCGATATTC ACACCAAGCG CCAACCTGAC TGAGATATCC TCCTGCACCA TCATCCCTCC ACCCTGTTTA GTTCTGCTCA CCCTCAGTGT TCTCATCAAT AATCCACTCC CCTCACAGGC GCGTTTGGGA CCCCATGTTC TATGCTCTCA CAGGACCTTT TGCTTGATTT TTCACTGTAC TTAGGTCAGT TTGCAGTTAT TAAGTGACTG AGCAATGTCT GGCTTCTCCA 65 GTAGACTGTC AGCTCCTAGC CATTGTATAC CTAGCACCGC TGTGTGGGAG CACGTGACAA ACGTCCAGTG AGTCAGGGAC TCAGCAGTCT CCATTTCTCC GCCCTGCTGG AGAATGCGTG TATTTGGCAA TCCCCAGCCC WO 00/62736 PCT/US00/08020 286 CTGTGCCATC TAACCATCT11 TT1C'TCTCTG TTCAGCCCAG GTGTGGCCTC ACTCACATCC CACTCTGAGT CCAAATGTTC TCTCCCTGGA AGATATCAAT G'ITCTGTCT GTTCGTGAGG ACTCCGTGCC CACCACGGCC TCTCAGGT GAGTCAAAGG GATTCCTCAG TTCACTAGTT AGGGGAGGTG GGCAGACACC CTGGAGAACT CCCTGGAAAG CTCAACTCTC ATGCCCCGGA CAACAGTTGA AGGAACCATG GTGATGTTAA GCCCAAAGAC 5 AAAACCTCTC AGGTGTCCAA GTCCCTGTTG GAATCTTGGG AGCAGAGGGA ATGTTCTGTG GTCTAGAGGA AGAGGGGCTC AGGGAGGAGA AGGGCACATT CCTGGTTGTT ATATG'TI'CT ATCTATCCCA GATGAACTI'G GAAGTGAAGG GAAGAGAGTT AAACATTAAA GTAAATACCC AGTGGATCAG ACAGCAATGT GCCAGATTGC CTITGGAAACA AAATATCTCC AACACATGGC TGACATTTGG TGGGAGATCA GAACACCCTA AAGAGAGAAT TTAAGGGGAG GGGGAGGAGG ACCTGAGCCA GAGTAGAAGC AGAGGATAGG GAGATCTGTT CTTGGGGACA 10 GCAnY7GCAA GAAACAAGGC TGAGGGGTCC ACTCCAACCT CTCCACCCTG CTGCAGGTGC TGCCTATGAT GAAGATGAGC AGATGGCCAT CTCAGCTGGG GCCACAGTGC ACTGGACCTA TAG3TTCCAA TTCCGCACTC AGCAGGCATC TTTCTGATGA TCCGATGGCT TCTCAGAGCC AGGGATGGGC CAGGATCCAT CCCCYTGGCT ACTGTCTTGC TGAGAAAT ATAAGCAGCA TCTGGTGCTA TAC'TTTGGTC TCTAGTGAGT TAGCTCATGA AAGATGATAG ACTCTCCAAG CCAGGGGTAT GCAGGAAATG GGITITTGT AGCTACAGAA ATGGGGFTGA 15 GGGTTGGACC AAGGGACTAC CCAGGGGAAG TCTT1ACC'ITC AGAGGACTCT GGAAAGGAGG CTGCAAGTfT TCATGGGTCA AGAATTCAGA GCCCAGTAGA GACAGCTTAT CTCTGrTCCA AGATGTCTGG GGCCTTGGTT GGAAGATTCA AAGGCTAGGA AACCAGGAGC CACCAAAAGC GTAACTGGGG CCAGAGGATC CACTI7CAAG GTGGCAAGTT GGTTCCCCCC ATGTGGCTGC TT1GAGTATCC TCACATGGCG GCTCACATCC TTCCAAGTAA GCAATGCAAA AGGCCAAGAA AGATGCTGCA AAGATGTTAT GACCTAGCCT CAGAAATCAC ACACCATCCC 20 TGCCACCATT AGTAAGAAGT CCAGCCCACG TCCAGGAGAA GAGGAAGCAG A'PrCCTCC'rr 'I1GAAATGAA GAATATCAAG TAAT-TCGGGG GGCATATGAA AGCCACCACA CACCACAGGG ATCTITTAG AGCATACTTC TTATACCATC ACTGTAGTTC CTTAAGACTC AGGGGCAAAG CCTCACTrCC TTAGCACCCA GTGAAGACCA CGCTTACTCC CTCACTCAAC CTCTIGCTAC TTCCCACCTC TCCTGTCCAA CATCTAGTGT CACTT'CCAG AACATACCAA CAGCTCCCC AG'I1CTGTGC CTCTGCTCAG GCTGTrCCCC CTGCCTGGTC CACTGTCCT 25 CC'FrCTTGTC CGGTCAAAAT GCTTCTTATC CT-FCAAGACC CAGCTCTAGA GTCACCTCCA ACCCCTTACC CACCAGCCCC CTCTCCAAGT CTGTGTCCCA CAACCCCCCT GCTCCCTCCA GGGCACCCTC CACCCTCTGG GCCACAGTTG TCAGGAGTCA GGCAGGGCAG GGGCCGGGTG GTGTCTrC'r TGTGT~rCT7G CACTCAGGGC AGAGCTCAGC ACAGAGCAGA CGCTCAAAAA ACATrAAAG GATAGAAGCA Tr1GA TrGTG GGTCCCCCAG TCTGGCTCCA GGATGCCAGC CAGCTGCTCC TAGAAGCAAA CGGACT=C CTGGGAAATC CCAGAGGTGA 30 TGATCAGTAA TCTCTCCCGT GACTCGTAGT TCAGcTcTrc CTCCATGAGC CTGACTATCA GTGGACCTTC CAGAAAGAGC CCCTITI'CCT TCTCTCACCC ACAGCACAGG GCACTGGGAA AATGCCCAAT GAGTCCTGCC TCTGGGTTGT GC1TrGGACT TTCAGTGTG TCTCGCATCC ACTCTTCAAC TrGAATGI7G CAACAGCCAT GAAAAAAGAA ATGCAAAGCG ATI'CAGGATG AGAGCAATAC CCTACTCCAA AGAAGGCAAC ATAGAAGCTC AGAGAGATCA AGCAATFGC CCAAGACCAC ACAGCTAGGA GTGGAACTCA TGGCTGTCCA AGCCCCATGC 35 CTCTGCTGAA GGTAGAGATG AATTACAGCA ACAAGTCTAG AAAGGTGCCT GCCCTATGGT CTGTGAGTCT TGCCTAAGAA TGAAAGAGGA GCCAGTGGGT TAAAGATGAG GTCACCAACA ACGGTGGTGT TGGAGFTTAC CACTGATAAT AAGGGTGCAA AATGTAAATT ACTAATGYIT ATTGAGCCTA GTGCAGTGCG TGGGGCATTT TGCACATTGT CTCTGATCCC TATGACAACC CTGAGAGGTA GTGGTJAA CTGCCATGI1 ACAGGTGAGG TCATTGTGGT TCAAGGACGT TAAGTAACTT CCCCAGCGTG ACACGGCTTA TAAGTAAGGC AGCCAGGATG 40 TGAACCCAGT AGGACTATCT GGCTGCAAAG TCCCCACCCC CCTCGCCATC TGTATCCTCC AATCACTTCA GTGC'1TTGCT GCATAGAAGG TAACGGAAAT CACGATGCCA CAGACTGTCC AGGAAGACAG AAACTAGGCA GATGGGCTGG CCATGGTCTC CAAGCCAGAC TGGAATCTCC AGGTCTGGAA TGATATCATT TITCTC'TrT AATAAATTAA CTCACCCACC ACACGGCTIT GAGAGGCTCA AAGTrGACCA ACTCCC'FrGG GAGGGCCCCG GTTGATAAGG AAGGAACGTG AATCCTCCCA TCACGGAAGC TTCAAGGAGG TCAAGGGTCC AACACTTGAG 45 A'ITGTrAGTG CTGTTGGTGG ATACTGGCCA AGGAAATATC CCAGTGGAGC CTCGAGATGA AGAACATGAG GCCCCCGT11 AGAACCAAGG ATCAGAGGGG GCTCTGTAAG ACCCAGGGGA GTCAGGTGCA CTGGAGCGCG GGCATGCAGA AAACAGCCTG AGCTCCACCT CGGCTTCTCC ITGTCCTGGC TGGTTGTCCT TAACCCCTGT CTCCTTCTGG ACCAGThTr GTCCTrCCCT TGTGACCGCT GAGGGGTAAC AGCCTC'L=C CAC 1TCTTF CAGCGCCGAC ATGCTCAATG TCACCTTGCA AGGGCCCACT CTTAACGGGA CCTITGCCCA GAGCAAATGC 50 CCCCAAGTGG AGTGGCTGGG CTGGCTCAAC ACCATCCAGC CCCCCTTCCT CTGGGTGCTG TTCGTGCTGG CCACCCTAGA GAACATCTTI7 GTCCTCAGCG TCTTCTGCCT GCACAAGAGC AGCTGCACGG TGGCAGAGAT CTACCTGGGG AACCTGGCCG CAGCAGACCT GATCCTGGCC TGCGGGCTGC CCTTCTGGGC CATCACCATC TCCAACAACT TCGACTGGCT CYITGGGGAG ACGCTCTGCC GCGTGGTGAA TGCCA'I1ATC TCCATGAACC TGTACAGCAG CATCTGTIMC CTGATGCTGG TGAGCATCGA CCGCTACCTG GCCCTGGTGA AAACCATGTC 55 CATGGGCCGG ATGCGCGGCG TGCGCTGGGC CAAGCTCTAC AGCTT1GGTGA TCTGGGGGTG TACGCTGCTC CTGAGCTCAC CCATGCTGGT GTTCCGGACC ATGAAGGAGT ACAGCGATGA GGGCCACAAC GTCACCGCYI7 GTGTCATCAG CTACCCATCC CTCATCTGGG AAGTGTTCAC CAACATGCTC CTGAATGTCG TGGGCTTCCT GCTGCCCCTG AGTGTCATCA CC'I7CTGCAC GATGCAGATC ATGCAGGTGC TGCGGAACAA CGAGATGCAG AAGTI7CAAGG AGATCCAGAC GGAGAGGAGG GCCACGGTGC TAGTCCTGGT TGTGCTGCTG CTATrCATCA 60 TCTGCTGGCT GCCCTTCCAG ATCAGCACCT TCCTGGATAC GCTGCATCGC CTCGGCATCC TCTCCAGCTG CCAGGACGAG CGCATCATCG ATGTAATCAC ACAGATCGCC TCCTTCATGG CCTACAGCAA CAGCTGCCTC AACCCACTGG TGTACGTGAT CGTGGGCAAG CGCTTCCGAA AGAAGTCTfG GGAGGTGTAC CAGGGAGTGT GCCAGAAAGG GGGCTGCAGG TCAGAACCCA TTCAGATGGA GAACTCCATG GGCACACTGC GGACCTCCAT CTCCGTGGAA CGCCAGATTC ACAAACTGCA GGACTGGGCA GGGAGCAGAC AGTGAGCAAA CGCCAGCAGG 65 GCTGCTGTGA ATIGTGTAA GGATTGAGGG ACAGTTGc L1? YICAGCATGG GCCCAGGAAT GCCAAGGAGA CATCTATGCA CGACCTrGGG AAATGAG'ITG ATGTCTCCGG TAAAACACCG GAGACTAATT CCTGCCCTGC WO 00/62736 PCT/USOO/08020 287 CCAATTTTGC AGGGAGCATG GCTGTGAGGA TGGGGTGAAC TCACGCACAG CCAAGGACTC CAAAATCACA ACAGCATTAC TGTTCTTATT TGCTGCCACA CCTGAGCCAG CCTGCTCCTT CCCAGGAGTG GAGGAGGCCT GGGGGCAGGG AGAGGAGTGA CTGAGCTTCC CTCCCGTGTG TTCTCCGTCC CTGCCCCAGC AAGACAACTr AGATCTCCAG GAGAACTGCC ATCCAGCTTT GGTGCAATGG CTGAGTGCAC AAGTGAGTTG TTGCCCTGGG 5 TTCTTTAAT CTATTCAGCT AGAACTTTGA AGGACAATTT CTTGCATTAA TAAAGGTTAA GCCCTGAGGG GTCCCTGATA ACAACCTGGA GACCAGGATT TTATGGCTCC CCTCACTGAT GGACAAGGAG GTCTGTGCCA AAGAAGAATC CAATAAGCAC ATATTGAGCA CTTGCTGTAT ATGCAGTATT GAGCACTGTA GGCAAGAGGG AAGAAAGAGA AGGAGCCATC TCCATCTTGA AGGAACTCAA AGACTCAAGT GGGAACGACT GGGCACTGCC ACCACCAGAA AGCTGTTCGA TGAGACGGTC GAGCAGGGTG CTGTGGGTGA TATGGACAGC AGAAGGGGGA 10 GCCAGGTTCC AGCTCACCAA TACTATTGCA CACCACCTGT CCTGCCTC -3' (FRAQ. NO: _) (SEQ. ID NO 2441) 5'-CAGATTCACA AACTGCAGGA CTGGGCAGGG AGCAGACAGT GAGCAAACGC CAGCAGGGCT GCTGTGAATT TGTGTAAGGA TTGAGGGACA GTTGCTTTTC AGCATGGGCC CAGGAATGCC AAGGAGACAT CTATGCACGA CCT'TGGGAAA TGAGTTGATG TCTCCGGTAA AACACCGGAG ACTAATTCCT GCCCTGCCCA ATTTTGCAGG GAGCATGGCT GTGAGGATGG GGTGAACTCA CGCACAGCCA AGGACTCCAA AATCACAACA GCATTACTGT 15 TCTTATGC TGCCACACCT GAGCCAGCCT GCTCCTTCCC AGGAGTGGAG GAGGCCTGGG GGGAGGGAGA GGAGTGACTG AGCTTCCCTC CCGTGTGTTC TCCGTCCCTG CCCCAGCAAG ACAACTTAGA TCTCCAGGAG AACTGCCATC CAGCTTTGGT GCAATGGCTG AGTGCACAAG TGAGTTGTTG CCCTGGGTTT CTTTAATCTA TTCAGCTAGA ACTTTGAAGG ACAATTTCTT GCATTAATAA AGGTTAAGCC CTGAGGGGTC CCTGATAACA ACCTGGAGAC CAGGATTTTA TGGCTCCCCT CACTGATGGA CAAGGAGGTC TGTGCCAAAG AAGAATCCAA 20 TAAGCACATA TTGAGCACTT GCTGTATATG CAGTATTGAG CACTGTAGGC AAGACCCAAG AAAGAGAAGG AGCCATCTCC ATCTTGAAGG AACTCAAAGA CTCAAGTGGG AACGACTGGG CACTGCCACC ACCAGAAAGC TGTTCGACGA GACGGTCGAG CAGGGTGCTG TGGGTGATAT GGACAGCAGA AGGGGGAGAC CAAGGTTCCA GCTCAACCAA TAACTATTGC ACAACCACCT GTCCCTGCCT CAGTTCCCTT TTATGTAACA TGAAGTCGTT GTGAGGGTTA AAGGCAGTAA CAGGTATAAA GTACTTAGAA AAGCAAAGGG TGCTACGTAC ATGTGAGGCA 25 TCATTACGCA GACGTAACTG GGATATGTTT ACTATAAGGA AAAGACACTG AGGTCTAGAA ATAGCTCCGT GGAGCAGAAT CAGTATTGGG AGCCGGTGGC GGTGTGAAGC ACCAGTGTCT GGCACACAGT AGGTGCTCAT TGGCTCCCTT CCACCTGTCA TTCCCACCAC CCTGAGGCCC CAACCGCCAC ACACACAGGA GCATTTGGAG AGAAGGCCAT GTCTTCAAAG TCTGATTTGT GATGAGGCAG AGGAAGATAT TTCTAATCGG TCTTGCCCAG AGGATCACAG TGCTGAGACC CCCCACCACC AGCCGGTACC TGGGAAGGGG GAGAGTGCAG GCCTGCTCAG 30 GGACTGTTCC TGTCTCAGCA ACCAAGGGAT TGTTCCTGTC AATCAATGGT TTATTGGAAG GTGGCCCAGT ATGAGCCCTA GAAGAGTGTG AAAAGGAATG GCAATGGTGT TCACCATCGG CAGTGCCAGG GCAGCACTCA TTCACTTGAT AAATGAATAT TTATTAGCTG GTTGGAGAGC TAGAACCTGG AGAGCTAGAA CCTGGAGAAC TAGAACCTGG AGGGCTAGAA CCTGGAGAGG CTAGAACCAA GAAGGGCTAG AACCTGGAGG GGCTAGAACC TAGAGAAGCT AAAACCTGAG CTAGAAGCTG GAGGACTAGA ACCTGGAGGG CTGGAATCTG AAGGGCTAGA 35 ACCTGGAGGG CTGGAATCTG GAGAGCTAGA ACCTGGAGGG CTAGAACCTG GAGGGCTAGA ACCTAGAAGG GCTAGAACCT GGAGGGCTGG AATCTGGAGA GCTAGAACCT GGAGGGCTAG AACCTGGAGG GCTAGAACCT AGAAGGGCTA GAACCTGGAG GGCTAGAACC TGGCAGGTTA GAACCTAGAA GGGCTAGAAC CTGGAGAGCC AGAACCTGGA GGGCTAGAAC CTGGAAGGGC TAGAACCTGT AGAGCTAGAA CATGGAGAGC TAGAACCCGG CAGGCTAGAA CCTGGCAAGC TAGAACCTGG AGGGAATGAA CCTGGAGGGC TAGAACCTGG AGAATGAGAA 40 AAATTTACAT GGCAAAGAGC CCATAAATCC TGACCAATCC AACTCTGAAT TTTAAAGCAA AAGCGTGAAA AAAAAGATTC CCTCCTTACC CCCAACCCAC TCTTITTCC CACCACCCAC TCTCCTCTGC CTCAGTAAGT ATCTGGAGGA AGAAAACAGG TGAAAGAAGA AGTAAAAACC ATTTAGTATT AGTATTAGAA TGAAGTCAAA CTGTGCCACA CATGGTGAAT GAAAAAAAAA AAAAAGAGGC TGTGTTTGT CACACAGGGC AGTCATTCAG CACCAGAGCA CGTGATGGTC TGAGACTCTC TTAGGAGCAG AGCTCTGCCG CAATGGCCAT GTGGGGATCC 45 ACACCTGGTC TGAGGGGCAA CTGAGTCTGC GGGAGAAGAG CGGCCCTATG CATGGTGTAG ATGCCCTGAT AAAGAACATC TGTCCTGTGA AAGACTCAAT GAGCTGTTAT GTTGTAAACA GGAAGCATTT CACATCCAAA CGAGAAAATC ATGTAAACAT GTGTCTTTTC TGTAGAGCAT AATAAATGGA TGAGGTTTTT GCAAAAAAAA AAAAAAAAA -3' (FRAQ. NO: ) (SEQ. ID NO 2431) 5'-GGTGBCBTTGBGCBTGTCGGCGC-3' (FRAG. NO:2276) (SEQ. ID NO:2289) 50 5'-GGTCCCGTTBBGBGTGGGCCC-3' (FRAG. NO:2277) (SEQ. ID NO:2290) 5'-GCCAGCCCAGCCACTCCACTTGGGGGC-3' (FRAG. NO:2278) (SEQ. ID NO:2291) 5'-GGGTGGCCAGCACGAACAGCACCCAGAGGAAGGGGGGC-3' FRAGG. NO:2279) (SEQ. ID NO:2292) 5'-GGCCCAGAAGGGCAGCCCGCAGGCCAGGATCAGGTCTGCTGCGGCC-3'(FRAG.NO:2280)(SEQ.ID NO:2293) 5'-GGAGATAATGGCATTCACCACGCGGC-3' (FRAG. NO:2281) (SEQ. ID NO:2294) 55 5'-GGCCCAGCGCACGCCGCGCATCCGGCCC-3' (FRAG. NO:2282) (SEQ. ID NO:2295) 5'-GGGTTCTGACCTGCAGCCCCC-3' (FRAG. NO:2283) (SEQ. ID NO:2296) 5'-GTCTCCTTGGCATTCCTGGGCCC-3' (FRAG. NO:2284) (SEQ. ID NO:2297) 5'-CAGTCACTCCTCTCCCTGCCCCC-3' (FRAG. NO:2285) (SEQ. ID NO:2298) 5'-CTTFGCTGGGGCAGGGACGG-3' FRAGG. NO:2286) (SEQ. ID NO:2299) 60 5'-GGTGBCBTTGBGCBTGTCGGCGC-3' (FRAG. NO:2287) (SEQ. ID NO:2300) 5'-GGTCCCGTTBBGBGTGGGCCC-3' FRAGG. NO:2288) (SEQ. ID NO:2301) 5'-GCCAGCCCAGCCACTCCACTTGGGGGC-3' FRAGG. NO:2289) (SEQ. ID NO:2302) 5'-GGGTGGCCAGCACGAACAGCACCCAGAGGAAGGGGGGC-3' FRAGG. NO:2290) (SEQ. ID NO:2303) 5'-GGCCCAGAAGGGCAGCCCGCAGGCCAGGATCAGGTCTGCTGCGGCC-3'(FRAG.NO:2291)(SEQ.ID NO:2304) 65 5'-GGAGATAATGGCATTCACCACGCGGC-3' FRAGG. NO:2292) (SEQ. ID NO:2305) WO 00/62736 PCT/USOO/08020 288 5'-GGCCCAGCGCACGCCGCGCATCCGGCCC-3' (FRAG. NO:2293) (SEQ. ID NO:2306) 5'-GGGTTCTGACCTGCAGCCCCC-3' (FRAG. NO:2294) (SEQ. ID NO:2307) 5'-GTCTCCTTGGCATTCCTGGGCCC-3' (FRAG. NO:2295) (SEQ. ID NO:2308) 5'-CAGTCACTCCTCTCCCTGCCCCC-3' (FRAG. NO:2296) (SEQ. ID NO:2309) 5 5'-CTTGCTGGGGCAGGGACGG-3' (FRAG. NO:2297) (SEQ. ID NO:2310) 5'-CCGTGTTGTCBGTGGTGCTG-3' (FRAG. NO:2298) (SEQ. ID NO:2311) 5'-CCCGTTTGBGGTBTGGC-3' (FRAG. NO:2299) (SEQ. ID NO:2312) 5'-GCTCCBCCBBTTCCCTTTTCTCC-3' (FRAG. NO:2300) (SEQ. ID NO:2313) 5'-TTGTTTTCCGTTTCTCTTG-3' (FRAG. NO:2301) (SEQ. ID NO:2314) 10 5'-CCGTCTGTGGTT-3' (FRAG. NO:2302) (SEQ. ID NO:2315) p2 Adrenergic Receptor Kinase Nucleic Acids and Antisense Oligonucleotide Fragments 5'- GCCGCCGCCG CCAAGATGGC GGACCTGGAG GCGGTGCTGG CCGACGTGAG CTACCTGATG GCCATGGAGA AGAGCAAGGC CACGCCGGCC GCGCGCGCCA GCAAGAAGAT ACTGCTGCCC GAGCCCAGCA TCCGCAGTGT CATGCAGAAG TACCTGGAGG ACCGGGGCGA GGTGACCTTT GAGAAGATCT TTTCCCAGAA 15 GCTGGGGTAC CTGCTCTTCC GAGACTTCTG CCTGAACCAC CTGGAGGAGG CCAGGCCCTT GGTGGAATTC TATGAGGAGA TCAAGAAGTA CGAGAAGCTG GAGACGGAGG AGGAGCGTGT GGCCCGCAGC CGGGAGATCT TCGACTCATA CATCATGAAG GAGCTGCTGG CCTGCTCGCA TCCCTTCTCG AAGAGTGCCA CTGAGCATGT CCAAGGCCAC CTGGGGAAGA AGCAGGTGCC TCCGGATCTC TTCCAGCCAT ACATCGAAGA GATTGTCAA AACCTCCGAG GGGACGTGTT CCAGAAATTC ATTGAGAGCG ATAAGTTCAC ACGGTTITTGC CAGTGGAAGA 20 ATGTGGAGCT CAACATCCAC CTGACCATGA ATGACTTCAG CGTGCATCGC ATCATTGGGC GCGGGGGCTT TGGCGAGGTC TATGGGTGCC GGAAGGCTGA CACAGGCAAG ATGTACGCCA TGAAGTGCCT GGACAAAAAG CGCATCAAGA TGAAGCAGGG GGAGACCCTG GCCCTGAACG AGCGCATCAT GCTCTCGCTC GTCAGCACTG GGGACTGCCC ATTCATTGTC TGCATGTCAT ACGCGTTCCA CACGCCAGAC AAGCTCAGCT TCATCCTGGA CCTCATGAAC GGTGGGGACC TGCACTACCA CCTCTCCCAG CACGGGGTCT TCTCAGAGGC TGACATGCGC 25 TTCTATGCGG CCGAGATCAT CCTGGGCCTG GAGCACATGC ACAACCGCTT CGTGGTCTAC CGGGACCTGA AGCCAGCCAA CATCCTTCTG GACGAGCATG GCCACGTGCG GATCTCGGAC CTGGGCCTGG CCTGTGACTT CTCCAAGAAG AAGCCCCATG CCAGCGTGGG CACCCACGGG TACATGGCTC CGGAGGTCCT GCAGAAGGGC GTGGCCTACG ACAGCAGTGC CGACTGGTTC TCTCTGGGGT GCATGCTCTT CAAGTTGCTG CGGGGGCACA GCCCCTTCCG GCAGCACAAG ACCAAAGACA AGCATGAGAT CGACCGCATG ACGCTGACGA TGGCCGTGGA 30 GCTGCCCGAC TCCTTCTCCC CTGAACTACG CTCCCTGCTG GAGGGGTTGC TGCAGAGGGA TGTCAACCGG AGATTGGGCT GCCTGGGCCG AGGGGCTCAG GAGGTGAAAG AGAGCCCCTT TTTCCGCTCC CTGGACTGGC AGATGGTCTT CTTGCAGAAG TACCCTCCCC CGCTGATCCC CCCACGAGGG GAGGTGAACG CGGCCGACGC CTTCGACATT GGCTCCTITCG ATGAGGAGGA CACAAAAGGA ATCAAGTTAC TGGACAGTGA TCAGGAGCTC TACCGCAACT TCCCCCTCAC CATCTCGGAG CGGTGGCAGC AGGAGGTGGC AGAGACTGTC TTCGACACCA 35 TCAACGCTGA GACAGACCGG CTGGAGGCTC GCAAGAAAGC CAAGAACAAG CAGCTGGGCC ATGAGGAAGA CTACGCCCTG GGCAAGGACT GCATCATGCA TGGCTACATG TCCAAGATGG GCAACCCCTT CCTGACCCAG TGGCAGCGGC GGTACTTCTA CCTGTTCCCC AACCGCCTCG AGTGGCGGGG CGAGGGCGAG GCCCCGCAGA GCCTGCTGAC CATGGAGGAG ATCCAGTCGG TGGAGGAGAC GCAGATCAAG GAGCGCAAGT GCCTGCTCCT CAAGATCCGC GGTGGGAAAC AGTTCATT GCAGTGCGAT AGCGACCCTG AGCTGGTGCA GTGGAAGAAG 40 GAGCTGCGCG ACGCCTACCG CGAGGCCCAG CAGCTGGTGC AGCGGGTGCC CAAGATGAAG AACAAGCCGC GCTCGCCCGT GGTGGAGCTG AGCAAGGTGC CGCTGGTCCA GCGCGGCAGT GCCAACGGCC TCTGACCCGC CCACCCGCCT CCAGGAAGCT ACCTGGAGGA GGTGAGTCTT AGCGGATGAG TAGGAGTTGT CCACGGAGGA AGGTACACAG AAGGGCTTCC AGGCCCAGGA AACAGCAGAG GCACAGAAGT GAGAATGGGT GGGTGAGTTG GTGGGGAAAC TCCAGGTGCA GAGGATGGTA GCGAAACAAA CTGGAGCATT AAGGTCCAAG TCCTCCAAGA 45 TCTTGACTTG CAGATTrAAGG AGTTTGTTCA CCTAATCTGC TTTGGGCAGA GTGTGGTGAG TCCTAGAGAC CCCTCTAGGT CTCTCCTCTC AGTAGCCCCA GAAGGCCTGG AGAGCTGCT CTGGGTGCCA AGCAGGCAGT GACTCCATCA GATCTAGATT TGGGAAAAGC ATCCCTGGTC AGGGCCTGCA TCAGGGCAGT GGCTGGCCAT GAGGACCCTG AGAAGTAGAC AGATTCACGG AGATTCTCAG GAGGCCAGAC AGGAGACTAT GGTGACAAAT TAGATTAGAG AAGGGGAGAG AATGAAGGAG CAGTTGGGGT AAAAGAAAAC TGAGGCTGAC ATGGGTATAT 50 GGGTGGCGAG TGACTCACCA CCCACTGAGA GGAGAACCTC ACAAGCTCTG ACATGCTCTG GTTCCAGGTT CTGTTGGGGC TGATCCAAGA TGGTAGCCTA GAGGTGCACA GAGATGGGGG CCTTGCTG CAAAAGGATG CTGGCTGCTG GCCCACAGCA TGGTAATGAG ATGAGCTT TATGTGCCCA GGGCTGGGAG GAGGGTCCTG TCACTGAA AGCAAAGAGA GGCTCTAGAG AGGGGCATGT TGAGATAGGA ATGCTGCCTT GAGACACCTG GCTTTCCCCA CTCTGGGTGG CTCTCAGCAG GGTGGGTC CCCTGCCAGG CAGCACTGAA CCTCTGTGCG 55 CTTCCGGCTG GGAGAGTTTT TACCGTAACT ACATGTGGAA CCATCCTGAA GGAACATCTG GATGGGATGG GGTACAGGGA AGGGAGCTGC CAAGAGTGCT GGCCAGGGAC CTGGGTCTAT GAGCTGGTTG GGGGGTGGGG TTGGGTGCAG GGTACTTGAT CCTGAGTGGG CCTTCTGCGG CCAGGATTGG TTCTAGAGTA GGAGGGGTGG GATCGGGGAT GGGGGAAGCC TGTAACTGCG CTGCAGTTGT CAGGTCCCAG GTTCTGGGTG ACCTACTAAG GATTCTGGGT CCAGTGTGGG TCCCAGGTrA GACGTCCTAG TCCTGAGTCC GTGTCCACAG TTCTGGGTGT 60 TGAGTCTAGG ACAGTGATCT GGAGTTGACA GTCCAATCTA GGTCTGAGTC CTGACCCCAA GTCTAGAGTT CAGGGTCATG GTAGTAGCCT AGGGTCAGAA TCAAGGTTGG GGTCAGTAAC CAGGATGGGA TCGAGGTCAT GGTCCAAAAT CTGGATCTGG GGACCTGTTG GGGGTCTGAG GTGAGTGTCG CAGTCTGGGT ATGGCGTTGG WO 00/62736 PCT/USOO/08020 289 AGACCCAGGG CTGTGATCTG AGGTCATGGT TAGAGTCTCA GGTGGTGGGC CAAGGTTTGA GTCTGGGGTC CTGTTTGGAG TCTGGTGTCA GGTCGTGGAC TGCGTCCAAG GTCAGGGAGT CCGGGGTTAT AGCCAGGGTC TGAGATGAAA GTCCCAGATG GTGTTCAGAG GTCTGAATCT GTGTCTTGGT GAGCGTCCAG GTTCCCTGTG ATCACGTTTG GTGTCAGGGC TGCGGCCCGA CTGGGGAGCC TGGGATCCAG AGATGTGACC CGAGGT7GTG 5 GTCAGAGAAT GGGTCTCGGG TCGTCTTCGT GCCGGGTCCC TGTCGTGTTC CAGGCCCGGG TCTCCGTCCA GCATCGAGGG CCGAGGTCAC GGCCAGGGTC TGAGCCCGCG GTCGCAGGTC TGGTTCGGGG TCAGATTCCG CGCGGCCTCC AGGGGGCGCC GTCGCCGCCC GGCTCGGCCC CTCGCGGGCT CGCTGGCGTT GTGCGCGGCA GGCGGGGCCG GAGGCGGCGG CGGCTCCGGG GGCGCGGGCC GGGCGGCGGC GGCGGCGGCG CCCCGACTGC AGTCCCGGCG GGAGCGGAGC GCGAAGCGCG GGGCCGGGCC CGGAGCCGGC GCCATGGGGC GGCGCCGCCT 10 GTGAGCGGCG GCGAGCGGAG CCGCGGGCGC CGAGCAGGGC CAGGCGGGAG CGTCGGCGCC CGAGGCCGAG CGAGCCGCGG CCGGGCCGGG CCGAGCGCCG AGCGAGCAGG AGCGGCGGCG GCGGCGGCGG CGGCGGGAGG AGGCAGCGCC GCCGCCAAGA TGGCGGACCT GGAGGCGGTG CTGGCCGACG TGAGCTACCT GATGGCCATG GAGAAGAGCA AGGCCACGCC GGCCGCGCGC GCCAGCAAGA AGATACTGCT GCCCGAGCCC AGGTGAGGAG AAGCT-3' (FRAG. NO:_) (SEQ. ID NO:2430) 15 5'-CCAGGAAGCT ACCTGGAGGA GGTGAGTCTT AGCGGATGAG TAGGAGTTGT CCACGGAGGA AGGTACACAG AAGGGCTrCC AGGCCCAGGA AACAGCAGAG GCACAGAAGT GAGAATGGGT GGGTGAGTTG GTGGGGAAAC TCCAGGTGCA GAGGATGGTA GCGAAACAAA CTGGAGCATT AAGGTCCAAG TCCTCCAAGA TCTTGACTTG CAGATTAAGG AGTTTGTTCA CCTAATCTGC TTTGGGCAGA GTGTGGTGAG TCCTAGAGAC CCCTCTAGGT CTCTCCTCTC AGTAGCCCCA GAAGGCCTGG AGAGCTGCTT CTGGGTGCCA AGCAGGCAGT GACTCCATCA 20 GATCTAGATT TGGGAAAAGC ATCCCTGGTC AGGGCCTGCA TCAGGGCAGT GGCTGGCCAT GAGGACCCTG AGAAGTAGAC AGATTCACGG AGATTCTCAG GAGGCCAGAC AGGAGACTAT GGTGACAAAT TAGATTAGAG AAGGGGAGAG AATGAAGGAG CAGTTGGGGT AAAAGAAAAC TGAGGCTGAC ATGGGTATAT GGGTGGCGAG TGACTCACCA CCCACTGAGA GGAGAACCTC ACAAGCTCTG ACATGCTCTG GTTCCAGGTT CTGTTGGGGC TGATCCAAGA TGGTAGCCTA GAGGTGCACA GAGATGGGGG CCTTGCTTTG CAAAAGGATG CTGGCTGCTG 25 GCCCACAGCA TGGTAATGAG ATTTGAGCTT TATGTGCCCA GGGCTGGGAG GAGGGTCCTG TCACTTTGAA AGCAAAGAGA GGCTCTAGAG AGGGGCATGT TGAGATAGGA ATGCTGCCTT GAGACACCTG GC'TTCCCCA CTCTGGGTGG CTCTCAGCAG GGTGGGTTTC CCCTGCCAGG CAGCACTGAA CCTCTGTGCG CTTCCGGCTG GGAGAGTTTT TACCGTAACT ACATGTGGAA CCATCCTGAA GGAACATCTG GATGGGATGG GGTACAGGGA AGGGAGCTGC CAAGAGTGCT GGCCAGGGAC CTGGGTCTAT GAGCTGGTTG GGGGGTGGGG TTGGGTGCAG 30 GGTACTTGAT CCTGAGTGGG CCTTCTGCGG CCAGGATTGG TT7CTAGAGTA GGAGGGGTGG GATCGGGGAT GGGGGAAGCC TGTAACTGCG CTGCAGTTGT CAGGTCCCAG GTTCTGGGTG ACCTACTAAG GATTCTGGGT CCAGTGTGGG TCCCAGGTTA GACGTCCTAG TCCTGAGTCC GTGTCCACAG TTCTGGGTGT TGAGTCTAGG ACAGTGATCT GGAGTTGACA GTCCAATCTA GGTCTGAGTC CTGACCCCAA GTCTAGAGTT CAGGGTCATG GTAGTAGCCT AGGGTCAGAA TCAAGGTTGG GGTCAGTAAC CAGGATGGGA TCGAGGTCAT GGTCCAAAAT 35 CTGGATCTGG GGACCTGTTG GGGGTCTGAG GTGAGTGTCG CAGTCTGGGT ATGGCGTTGG AGACCCAGGG CTGTGATCTG AGGTCATGGT TAGAGTCTCA GGTGGTGGGC CAAGGTGA GTCTGGGGTC CTGTTTGGAG TCTGGTGTCA GGTCGTGGAC TGCGTCCAAG GTCAGGGAGT CCGGGGTTAT AGCCAGGGTC TGAGATGAAA GTCCCAGATG GTGTTCAGAG GTCTGAATCT GTGTCTTGGT GAGCGTCCAG GTTCCCTGTG ATCACGTTTG GTGTCAGGGC TGCGGCCCGA CTGGGGAGCC TGGGATCCAG AGATGTGACC CGAGGTTGTG GTCAGAGAAT 40 GGGTCTCGGG TCGTCTTCGT GCCGGGTCCC TGTCGTGTTC CAGGCCCGGG TCTCCGTCCA GCATCGAGGG CCGAGGTCAC GGCCAGGGTC TGAGCCCGCG GTCGCAGGTC TGGTTCGGGG TCAGATTCCG CGCGGCCTCC AGGGGGCGCC GTCGCCGCCC GGCTCGGCCC CTCGCGGGCT CGCTGGCGTT GTGCGCGGCA GGCGGGGCCG GAGGCGGCGG CGGCTCCGGG GGCGCGGGCC GGGCGGCGGC GGCGGCGGCG CCCCGACTGC AGTCCCGGCG GGAGCGGAGC GCGAAGCGCG GGGCCGGGCC CGGAGCCGGC GCCATGGGGC GGCGCCGCCT GTGAGCGGCG 45 GCGAGCGGAG CCGCGGGCGC CGAGCAGGGC CAGGCGGGAG CGTCGGCGCC CGAGGCCGAG CGAGCCGCGG CCGGGCCGGG CCGAGCGCCG AGCGAGCAGG AGCGGCGGCG GCGGCGGCGG CGGCGGGAGG AGGCAGCGCC GCCGCCAAGA TGGCGGACCT GGAGGCGGTG CTGGCCGACG TGAGCTACCT GATGGCCATG GAGAAGAGCA AGGCCACGCC GGCCGCGCGC GCCAGCAAGA AGATACTGCT GCCCGAGCCC AGGTGAGGAG AAGCT-3' (FRAG. NO:_) (SEQ. ID NO:2429) 50 5'-GCCGCCGCCG CCAAGATGGC GGACCTGGAG GCGGTGCTGG CCGACGTGAG CTACCTGATG GCCATGGAGA AGAGCAAGGC CACGCCGGCC GCGCGCGCCA GCAAGAAGAT ACTGCTGCCC GAGCCCAGCA TCCGCAGTGT CATGCAGAAG TACCTGGAGG ACCGGGGCGA GGTGACCTTT GAGAAGATCT TT7CCCAGAA GCTGGGGTAC CTGCTCTTCC GAGACTTCTG CCTGAACCAC CTGGAGGAGG CCAGGCCCTT GGTGGAATTC TATGAGGAGA TCAAGAAGTA CGAGAAGCTG GAGACGGAGG AGGAGCGTGT GGCCCGCAGC CGGGAGATCT TCGACTCATA 55 CATCATGAAG GAGCTGCTGG CCTGCTCGCA TCCCTTCTCG AAGAGTGCCA CTGAGCATGT CCAAGGCCAC CTGGGGAAGA AGCAGGTGCC TCCGGATCTC TTCCAGCCAT ACATCGAAGA GATTTGTCAA AACCTCCGAG GGGACGTGTT CCAGAAATTC ATTGAGAGCG ATAAGTTCAC ACGGTTGC CAGTGGAAGA ATGTGGAGCT CAACATCCAC CTGACCATGA ATGACTTCAG CGTGCATCGC ATCATTGGGC GCGGGGGCTT TGGCGAGGTC TATGGGTGCC GGAAGGCTGA CACAGGCAAG ATGTACGCCA TGAAGTGCCT GGACAAAAAG CGCATCAAGA 60 TGAAGCAGGG GGAGACCCTG GCCCTGAACG AGCGCATCAT GCTCTCGCTC GTCAGCACTG GGGACTGCCC ATTCATTGTC TGCATGTCAT ACGCGTTCCA CACGCCAGAC AAGCTCAGCT TCATCCTGGA CCTCATGAAC GGTGGGGACC TGCACTACCA CCTCTCCCAG CACGGGGTCT TCTCAGAGGC TGACATGCGC TTCTATGCGG CCGAGATCAT CCTGGGCCTG GAGCACATGC ACAACCGCTT CGTGGTCTAC CGGGACCTGA AGCCAGCCAA CATCCTTCTG GACGAGCATG GCCACGTGCG GATCTCGGAC CTGGGCCTGG CCTGTGACTT CTCCAAGAAG 65 AAGCCCCATG CCAGCGTGGG CACCCACGGG TACATGGCTC CGGAGGTCCT GCAGAAGGGC GTGGCCTACG ACAGCAGTGC CGACTGGTTC TCTCTGGGGT GCATGCTCT CAAGTTGCTG CGGGGGCACA GCCCCTTCCG WO 00/62736 PCT/USOO/08020 290 GCAGCACAAG ACCAAAGACA AGCATGAGAT CGACCGCATG ACGCTGACGA TGGCCGTGGA GCTGCCCGAC TCCTTCTCCC CTGAACTACG CTCCCTGCTG GAGGGGTTGC TGCAGAGGGA TGTCAACCGG AGATTGGGCT GCCTGGGCCG AGGGGCTCAG GAGGTGAAAG AGAGCCCCTT TTTCCGCTCC CTGGACTGGC AGATGGTCTT CTTGCAGAAG TACCCTCCCC CGCTGATCCC CCCACGAGGG GAGGTGAACG CGGCCGACGC CTTCGACATr 5 GGCTCCTTCG ATGAGGAGGA CACAAAAGGA ATCAAGTrAC TGGACAGTGA TCAGGAGCTC TACCGCAACT TCCCCCTCAC CATCTCGGAG CGGTGGCAGC AGGAGGTGGC AGAGACTGTC TTCGACACCA TCAACGCTGA GACAGACCGG CTGGAGGCTC GCAAGAAAGC CAAGAACAAG CAGCTGGGCC ATGAGGAAGA CTACGCCCTG GGCAAGGACT GCATCATGCA TGGCTACATG TCCAAGATGG GCAACCCCTT CCTGACCCAG TGGCAGCGGC GGTACTTCTA CCTGTTCCCC AACCGCCTCG AGTGGCGGGG CGAGGGCGAG GCCCCGCAGA GCCTGCTGAC 10 CATGGAGGAG ATCCAGTCGG TGGAGGAGAC GCAGATCAAG GAGCGCAAGT GCCTGCTCCT CAAGATCCGC GGTGGGAAAC AGTTCATTTT GCAGTGCGAT AGCGACCCTG AGCTGGTGCA GTGGAAGAAG GAGCTGCGCG ACGCCTACCG CGAGGCCCAG CAGCTGGTGC AGCGGGTGCC CAAGATGAAG AACAAGCCGC GCTCGCCCGT GGTGGAGCTG AGCAAGGTGC CGCTGGTCCA GCGCGGCAGT GCCAACGGCC TCTGACCCGC CCACCCGCCT-3' (FRAG. NO:_) (SEQ. ID NO:2428) 15 CCR-2 CC Chemokine Receptor Nucleic Acids and Antisense Oligonucleotide Fragments 5'-CTTGTGAAG AAGGAATTGG CAACACTGAA ACCTCCAGAA CAAAGGCTGT CACTAAGGTC CCGCTGCCTT GATGGATTAT ACACTTGACC TCAGTGTGAC AACAGTGACC GACTACTACT ACCCTGATAT CTTCTCAAGC CCCTGTGATG CGGAACTTAT TCAGACAAAT GGCAAGTTGC TCCTTGCTGT CTTTTATrGC CTCCTGTTG TATTCAGTCT TCTGGGAAAC AGCCTGGTCA TCCTGGTCCT TGTGGTCTGC AAGAAGCTGA GGAGCATCAC 20 AGATGTATAC CTCTTGAACC TGGCCCTGTC TGACCTGCTT TTTGTCTTCT CCTTCCCCTT TCAGACCTAC TATCTGCTGG ACCAGTGGGT GTTrGGGACT GTAATGTGCA AAGTGGTGTC TGGCTTTTAT TACATTGGCT TCTACAGCAG CATGTTTC ATCACCCTCA TGAGTGTGGA CAGGTACCTG GCTGTTGTCC ATGCCGTGTA TGCCCTAAAG GTGAGGACGA TCAGGATGGG CACAACGCTG TGCCTGGCAG TATGGCTAAC CGCCATTATG GCTACCATCC CATTGCTAGT GTTTTACCAA GTGGCCTCTG AAGATGGTGT TCTACAGTGT TATTCATTTT 25 ACAATCAACA GACTTTGAAG TGGAAGATCT TCACCAACTT CAAAATGAAC ATTTTAGGCT TGTTGATCCC ATTCACCATC TTTATGTTCT GCTACATTAA AATCCTGCAC CAGCTGAAGA GGTGTCAAAA CCACAACAAG ACCAAGGCCA TCAGGTTGGT GCTCATTGTG GTCATTGCAT CTTTACTTTT CTGGGTCCCA TTCAACGTGG TTCTTCCT CACTTCCTTG CACAGTATGC ACATCTTGGA TGGATGTAGC ATAAGCCAAC AGCTGACTTA TGCCACCCAT GTCACAGAAA TCATTCCTT TACTCACTGC TGTGTGAACC CTGTTATCTA TGCTTTTGTT 30 GGGGAGAAGT TCAAGAAACA CCTCTCAGAA ATATTTCAGA AAAGTTGCAG CCAAATCTTC AACTACCTAG GAAGACAAAT GCCTAGGGAG AGCTGTGAAA AGTCATCATC CTGCCAGCAG CACTCCTCCC GTTCCTCCAG CGTAGACTAC ATTTTGTGAG GATCAATGAA GACTAAATAT AAAAAACATT TTCTTGAATG GCATGCTAGT AGCAGTGAGC AAAGGTGTGG GTGTGAAAGG TTTCCAAAAA AAGTTCAGCA TGAAGGATGC CGTGTGTGTT GTTGCCAACA CTTGGAACAC AATGACTGGA GACATAGTTG TGCATGCCTG GCACAACATC AAGCCTGTGA 35 TrGTGTTTAT TGATGATGTT GAACAAGTGG TGGCTTTGAG GGATTCTGTA TGCCAAGTGG AAAAAAAAGA TGTCTCCGGA ATTCGACAGG TTATCA-3' (FRAG. NO:_) (SEQ. ID NO:2462) CCR-4 CC Chemokine Receptor Nucleic Acids and Antisense Oligonucleotide Fragments 5'-TrTCATCTCT CCGGGCTTAT TTGCTGGTTTr CTCCGAATGC GGGCCTTGTC TGGTTCACGC TGGATCCCCA ACGCCTAGAA CAGTGCGTGG CACGCAGTTC GTCCTTCTAT AAATATCGGA CTAAATGCAT CTCTGTGATG 40 GTAATACCCA CACGGTGTTG TGAGAATGAA TGAGTGATTC TGTGCAAGTT CCTAGTGATC TGTTACAAAA AGTACTGGTC GCTAAATFAC TCTTATAATA AAGCATACTT TTAGGATAAT AAAGCACTAT TCGCGAATTG GTTACCGCTA TTATGAAATT ACTGAGCAAT ACATATCTAC ATCTGATCAG TCTCCAGAAT TATGCCAAAT CCTACCTTCT TCTGAAAGTA TCTCCTAATT ATCTGCACCT GACCCTAGTG ATGCTGTGAA TGTGCAAGTA TAGCTACATC CTCCGAAGGA AGGATCTTrA CTCCTTAC CTCCTGAATG GGCTGCGTCT GCTGAAAGCG 45 CGGGGGAATG GGCGGTTGGA AGCTTGGCCC TACTTCCAGC ATTGCCGCCT ACTGGTTGGG ITTACTCCAGC AAGTCACTCC CCTTCCCTGG GCCTCAGTGT CTCTACTGTA GCATTCCCAG GTCTGGAATT CCATCCACTT TAGCAAGGAT GGACGCGCCA CAGAGAGACG CGTTCCTAGC CCGCGCTrCC CACCTGTCTT CAGGCGCATC CCGCTTCCCT CAAACTTAGG AAATGCCTCT GGGAGGTCCT GTCCGGCTCC GGACTCACTA CCGACCACCC GCAAACAGCA GGGTCCCCTG GGCTTCCCAA GCCGCGCACC TCTCCGCCCC GCCCCTGCGC CCTCCTTCCT 50 CGCGTCTGCC CCTCTCCCCC ACCCCGCCTT CTCCCTCCCC GCCCCAGCGG CGCATGCGCC GCGCTCGGAG CGTGTTTA TAAAAGTCCG GCCGCGGCCA GAAACTTCAG ITGTTGGCT GCGGCAGCAG GTAGCAAAGT GACGCCGAGG GCCTGAGTGC TCCAGTAGCC ACCGCATCTG GAGAACCAGC GGTTACCATG GAGGGGATCA GTGTAAGTCC AGTTTCAACC TGCTTGTCA TAAATGTACA AACGTTTGAA CTTAGAGCGC AGCCCCTCTC CGAGCGGGCA GAAGCGGCCA GGACATTGGA GGTACCCGTA CTCCAAAAAA GGGTCACCGA AAGGAGTT 55 CTTGACCATG CCTATATAGT GCGGGTGGGT GGGGGGGGAG CAGGATTGGA ATCTTTTTrCT CTGTGAGTCG AGGAGAAACG ACTGGAAAGA GCGTTCCAGT GGCTGCATGT GTCTCCCCCT TGAGTCCCGC CGCGCGCGGC GGCTTGCACG CTGTTTGCAA ACGTAAGAAC ATTCTGTGCA CAAGTGCAGA GAAGGCGTGC GCGCTGCCTC GGGACTCAGA CCACCGGTCT CTTCCTTGGG GAAGCGGGGA TGTCTTGGAG CGAGTTACAT TGTCTGAATT TAGAGGCGGA GGGCGGCGTG CCTGGGCTGA CTTCCCAGGA GGAGATTGCG CCCGCTTTAA CTTCGGGGTT 60 AAGCGCCTGG TGACTGTTCT TGACACTGGG TGCGTGTTTG TTAAACTCTG TGCGGCCGAC GGAGCTGTGC CAGTCTCCCA GCACAGTAGG CAGAGGGCGG GAGAGGCGGG TGGACCCACC GCGCCGATCC TCTGAGGGGA TCGAGTGGTG GCAGCAGCTA GGAGTTGATC CGCCCGCGCG CTTTGGGTTT GAGGGGGAAA CCTTCCCGCC GTCCGAAGCG CGCCTCTTCC CCACGGCCGC GAGTGGGTCC TGCAGTTCGA GAGTTTGGGG TCGTGCAGAG GTCAGCGGAG TGGTTTGACC TCCCCTTTGA CACCGCGCAG CTGCCAGCCC TGAGATTTGC GCTCCGGGGA 65 TAGGAGCGGG TACGGGGTGA GGGGCGGGGG CGGTTAAGAC CGCACCTGGG CTGCCAGGTC GCCGCCGCGA WO 00/62736 PCT/USOO/08020 291 AGACTGGCAG GTGCAAGTGG GGAAACCGTT TGGCTCTCTC CGAGTCCAGT TGTGATGTTT AACCGTCGGT GGTTCCAGA AACCTTGA AACCCTCTTG CTAGGGAGTT TTTGGTCC TGCAGCGGCG CGCAATTCAA AGACGCTCGC GGCGGAGCCG CCCAGTCGCT CCCCAGCACC CTGTGGGACA GAGCCTGGCG TGTCGCCCAG CGGAGCCCCT GCAGCGCTGC TTGCGGGCGG TTGGCGTGGG TGTAGTGGGC AGCCGCGGCG GCCCGGGGCT 5 GGACGACCCG GCCCCCCGCG TGCCCACCGC CTGGAGGCTT CCAGCTGCCC ACCTCCGGCC GGGTTAACTG GATCAGTGGC GGGGTAATGG GAAGCCACCC GGGAGAGTGA. GGAAATGAAA CTrGGGGCGA GGACCACGGG TGCAGACCCC GTTACCTTCT CCACCCAGGA AAATGCCCCG CTCCCTAACG TCCCAAACGC GCCAAGTGAT AAACACGAGG ATGGCAAGAG ACCCACACAC CGGAGGAGCG CCCGCTTGGG GGAGGAGGTG CCGTTTGTTC ATTCTGAC ACTCCCGCCC AATATACCCC AAGCACCGAA GGGCCTTCGT TTTAAGACCG CATTCTCTTT 10 ACCCACTACA AGTTGCTTGA AGCCCAGAAT GGTGTATT TAGGCAGGCG TGGGAAAATT AAGTTTTTGC GCTTAGGAG AATGAGTCTT TGCAACGCCC CCGCCCTCCC CCCGTGATCC TCCCTTCTCC CCTCTTCCCT CCCTGGGCGA AAAACTTCTT ACAAAAAGTT AATCACTGCC CCTCCTAGCA GCACCCACCC CACCCCCCAC GCCGCCTGGG AGTGGCCTCT TTGTGTGTAT TTTTTTC CTCCTAAGGA AGGTITT I TCTTCCCTCT AGTGGGCGGG GCAGAGGAGT TAGCCAAGAT GTGACTTTGA AACCCTCAGC GTCTCAGTGC CCTTTTGTTC 15 TAAACAAAGA ATTTTGTAAT TGGTTCTACC AAAGAAGGAT ATAATGAAGT CACTATGGGA AAAGATGGGG AGGAGAGT7G TAGGATTCTA CATTAATTCT CTTGTGCCCT TAGCCCACTA CTTCAGAATT TCCTGAAGAA AGCAAGCCTG AATTGGTT TTAAATTGCT TTAAAAATTT TTTAACTG GGTTAATGCT TGCTGAATTG GAAGTGAATG TCCATTCCTT TGCCTCTTTT GCAGATATAC ACTTCAGATA ACTACACCGA GGAAATGGGC TCAGGGGACT ATGACTCCAT GAAGGAACCC TGTTTCCGTG AAGAAAATGC TAATTTCAAT AAAATCTTCC 20 TGCCCACCAT CTACTCCATC ATCTTCTTAA CTGGCATTGT GGGCAATGGA TTGGTCATCC TGGTCATGGG TTACCAGAAG AAACTGAGAA GCATGACGGA CAAGTACAGG CTGCACCTGT CAGTGGCCGA CCTCCTCTTT GTCATCACGC TTCCCTTCTG GGCAGTTGAT GCCGTGGCAA ACTGGTACTT TGGGAACTTC CTATGCAAGG CAGTCCATGT CATCTACACA GTCAACCTCT ACAGCAGTGT CCTCATCCTG GCCTTCATCA GTCTGGACCG CTACCTGGCC ATCGTCCACG CCACCAACAG TCAGAGGCCA AGGAAGCTGT TGGCTGAAAA GGTGGTCTAT 25 GTTGGCGTCT GGATCCCTGC CCTCCTGCTG ACTATTCCCG ACTTCATCTT TGCCAACGTC AGTGAGGCAG ATGACAGATA TATCTGTGAC CGCTTCTACC CCAATGACTT GTGGGTGGTT GTGTTCCAGT TTCAGCACAT CATGGTTGGC CTTATCCTGC CTGGTATTGT CATCCTGTCC TGCTATTGCA TTATCATCTC CAAGCTGTCA CACTCCAAGG GCCACCAGAA GCGCAAGGCC CTCAAGACCA CAGTCATCCT CATCCTGGCT TTCTTCGCCT GTTGGCTGCC TTACTACATT GGGATCAGCA TCGACTCCTT CATCCTCCTG GAAATCATCA AGCAAGGGTG 30 TGAGTTTGAG AACACTGTGC ACAAGTGGAT T7CCATCACC GAGGCCCTAG CTTTCTTCCA CTGTTGTCTG AACCCCATCC TCTATGCTTT CCTTGGAGCC AAATTTAAAA CCTCTGCCCA GCACGCACTC ACCTCTGTGA GCAGAGGGTC CAGCCTCAAG ATCCTCTCCA AAGGAAAGCG AGGTGGACAT TCATCTGTTT CCACTGAGTC TGAGTCTTCA AGTTTTCACT CCAGCTAACA CAGATGTAAA AGACTT17T TTATACGATA AATAACTTTT TTTTAAGTTA CACATTTTTC AGATATAAAA GACTGACCAA TATTGTACAG TTTATTGC TTGTTGGATT 35 TTTGTCTTGT GTTTCTTTAG TTTTTGTGAA GTTTAATTGA CTTATTTATA TAAATTTTTT TTGTTTCATA T'TGATGTGTG TCTAGGCAGG ACCTGTGGCC AAGTTCTTAG TTGCTGTATG TCTCGTGGTA GGACTGTAGA AAAGGGAACT GAACATTCCA GAGCGTGTAG TGAATCACGT AAAGCTAGAA ATGATCCCCA GCTGTTTATG CATAGATAAT CTCTCCATTC CCGTGGAACG TTTCCTGT TCTTAAGACG TGATTGCT GTAGAAGATG GCACTTATAA CCAAAGCCCA AAGTGGTATA GAAATGCTGG TTTTTCAGTT TTCAGGAGTG GGTTGATTTC 40 AGCACCTACA GTGTACAGTC TTGTATTAAG TTGTTAATAA AAGTACATGT TAAACTTACT TAGTGTTATG TTCTGATC TGTTGACATTr CTTGGCTA GTAGAAGACA AAAGTAATAC ATATGGTA TGCAAAGCAC TATCCTAGGT ATTTCATTGT AATATTAC TTACCCCTTA TCACAACTCT GATAGATTCT GCTTCTGTTA CTAATTACAT TTTATAGAAG AGGAAACGGA GGCACAGAAA GCCTAAGTAA CTTGGTIAAA GGCATGTAGT AAGTATCAAA TCCTGTATTT TAAACCAGGT AACATGACTT AACGAATCTG AAGCCTTCAC CACTTAAAT 45 TCAAATGGAA GTTAGAAAT GGCCAGCCAG CACCTATTTG TATGAAAGGT CATCTTTCAG AGGATAAGCA TGTATAAAGA AGAAAAGGTA TGCAGTCGTG TTTGGA'TT ACTCCACCAT C-3' FRAGG. NO:_) (SEQ. ID NO: 2463) CD-34 Nucleic Acids and Antisense Oligonucleotide Fragments 5'-AGGATGATGG TGATGGGGAA CTAAATGGGG AAATATGGAA GGTCACAGGA AAAGTTAACA CAAGTTAGCA AAAGTTAAC ATAACACAAA AAGGTCTTGC AGGAAAAAAA AAAGAAAAGA AAAGAAAGAA AAAGTCTCCA 50 AGAATGGTI7 GGACAGCCAA AATGAATACT TATAGTCACG TATACCTGCT CACTCCTGAC GCTTCACTCA CACACAGCAC AGGATCTGGT GAGGCTATCA TAAATGTGC CACATTGTGG TTAAGITTA CCTGATTAAC GAAATGCTCA CACTTCTAAA CTGAGGTCCT TACAGTAGAT TCC'TTGCA AGATTGTTAC TGGCTTACAA CTTAAAAATA AAGGAAAATC ACAAGGAAAG AAAAGTGGGG AAAAAATCGG AGGAAACTTG CCCCTGCCCT GGCCACCGGC AAGGCTGCCA CAAAGGGGTT AAAAGTTAAG TGGAAGTGGA GCT7GAAGAA GTGGGATGGG 55 GCCTCTCCAG GAAAGCTGAA CGAGGCATCT GGAGCCCGAA CAAACCTCCA CCTTTTTGG CCTCGACGGC GGCAACCCAG CCTCCCTCCT AACGCCCTCC GCCTTTGGGA CCAACCAGGG GAGCTCAAGT TAGTAGCAGC CAAGGAGAGG CGCTGCCTTG CCAAGACTAA AAAGGGAGGG GAGAAGAGAG GAAAAAAGCA AGAATCCCCC ACCCCTCTCC CGGGCGGAGG GGGCGGGAAG AGCGCGTCCT GGCCAAGCCG AGTAGTGTCT TCCACTCGGT GCGTCTCTCT AGGAGCCGCG CGGGAAGGAT GCTGGTCCGC AGGGGCGCGC GCGCAGGGCC CAGGATGCCG 60 CGGGGCTGGA CCGCGCTTTG CTTGCTGAGT TTGCTGC CCTTTTGG CCTCGACGGC GGCAACCCAG CCTCCCTCCT AACGCCCTCC GCCTTTGGGA CCAACCAGGG GAGCTCAAGT TAGTAGCAGC CAAGGAGAGG CGCTGCCTTG CCAAGACTAA AAAGGGAGGG GAGAAGAGAG GAAAAAAGCA AGAATCCCCC ACCCCTCTCC CGGGCGGAGG GGGCGGGAAG AGCGCGTCCT GGCCAAGCCG AGTAGTGTCT TCCACTCGGT GCGTCTCTCT AGGAGCCGCG CGGGAAGGAT GCTGGTCCGC AGGGGCGCGC GCGAGGGCCC AGGATGCCGC GGGGCTGGAC 65 CGCGCTTTGC TTGCTGAGTT TGCTGCCTTC TGGGTTCATG AGTCTTGACA ACAACGGTAC TGCTACCCCA GAGTTACCTA CCCAGGGAAC ATTCAAAT GTCTACAA ATGTATCCTA CCAAGAAACT ACAACACCTA GTACCCTTGG AAGTACCAGC CTGCACCCTG TGTCTCAACA TGGCAATGAG GCCACAACAA ACATCACAGA WO 00/62736 PCT/USOO/08020 292 AACGACAGTC AAATrCACAT CTACCTCTGT GATAACCTCA GTTTATGGAA ACACAAACTC TTCTGTCCAG TCACAGACCT CTGTAATCAG CACAGTGTTC ACCACCCCAG CCAACGTTTC AACTCCAGAG ACAACCTTGA AGCCTAGCCT GTCACCTGGA AATGTTTCAG ACCTCAAC CACTAGCACT AGCCTTGCAA CATCTCCCAC TAAACCCTAT ACATCATCTT CTCCTATCCT AAGTGACATC AAGGCAGAAA TCAAATGTrC AGGCATCAGA 5 GAAGTGAAAT TGACTCAGGG CATCTGCCTG GAGCAAAATA AGACCTCCAG CTGTGCGGAG TTTAAGAAGG ACAGGGGAGA GGGCCTGGCC CGAGTGCTGT GTGGGGAGGA GCAGGCTGAT GCTGATGCTG GGGCCCAGGT ATGCTCCCTG CTCCTTGCCC AGTCTGAGGT GAGGCCTCAG TGTCTACTGC TGGTCTTGGC CAACAGAACA GAAATTTCCA GCAAACTCCA ACTTATGAAA AAGCACCAAT CTGACCTGAA AAAGCTGGGG ATCCTAGATT TCACTGAGCA AGATGTTGCA AGCCACCAGA GCTATrCCCA AAAGACCCTG ATTGCACTGG TCACCTCGGG 10 AGCCCTGCTG GCTGTCTTGG GCATCACTGG CTATTTCCTG ATGAATCGCC GCAGCTGGAG CCCCACAGGA GAAAGGCTGG GCGAAGACCC TTATTACACG GAAAACGGTG GAGGCCAGGG CTATAGCTCA GGACCTGGGA CCTCCCCTGA GGCTCAGGGA AAGGCCAGTG TGAACCGAGG GGCTCAGAAA AACGGGACCG GCCAGGCCAC CTCCAGAAAC GGCCATTCAG CAAGACAACA CGTGGTGGCT GATACCGAAT TGTGACTCGG CTAGGTGGGG CAAGGCTGGG CAGTGTCCGA GAGAGCACCC CTCTCTGCAT CTGACCACGT GCTACCCCCA TGCTGGAGGT 15 GACATCTCTT ACGCCCAACC CTTCCCCACT GCACACACCT CAGAGGCTGT TCTTGGGGCC CTACACCTTG AGGAGGGGGC AGGTAAACTC CTGTCCTTTA CACATTCGGC TCCCTGGAGC CAGACTCTGG TCTTCTTTGG GTAAACGTGT GACGGGGGAA AGCCAAGGTC TGGAGAAGCT CCCAGGAACA ATCGATGGCC TTGCAGCACT CACACAGGAC CCCCTTCCCC TACCCCCTCC TCTCTGCCGC AATACAGGAA CCCCCAGGGG AAAGATGAGC TTTTCTAGGC TACAATC TCCCAGGAAG CTTTGATT TACCGTTTCT TCCCTGTATT TTCTTTCTCT 20 ACTTTGAGGA AACCAAAGTA ACCTTTTGCA CCTGCTCTCT TGTAATGATA TAGCCAGAAA AACGTGTTGC CTTGAACCAC TTCCCTCATC TCTCCTCCAA GACACTGTGG ACTTGGTCAC CAGCTCCTCC CTTGTTCTCT AAGTTCCACT GAGCTCCATG TGCCCCCTCT ACCATTTGCA GAGTCCTGCA CAGTTrTCTG GCTGGAGCCT AGAACAGGCC TCCCAAGTTT TAGGACAAAC AGCTCAGTTC TAGTCTCTCT GGGGCCACAC AGAAACTCTT TTTGGGCTCC TTTTTCTCCC TCTGGATCAA AGTAGGCAGG ACCATGGGAC CAGGTCTTGG AGCTGAGCCT 25 CTCACCTGTA CTCTTCCGAA AAATCCTCTT CCTCTGAGGC TGGATCCTAG CCTTATCCTC TGATCTCCAT GGCTTCCTCC TCCCTCCTGC CGACTCCTGG GTTGAGCTGT TGCCTCAGTC CCCCAACAGA TGCTTTTCTG TCTCTGCCTC CCTCACCCTG AGCCCCTTCC TTGCTCTGCA CCCCCATATG GTCATAGCCC AGATCAGCTC CTAACCCTTA TCACCAGCTG CCTCTTCTGT GGGTGACCCA GGTCCTTGTT TGCTGTTGAT TTCTTTCCAG AGGGGTTGAG CAGGGATCCT GGTCAATG ACGGTTGGAA ATAGAAATTT CCAGAGAAGA GAGTATTGGG 30 TAGATATTTT TTCTGAATAC AAAGTGATGT GTTTAAATAC TGCAATTAAA GTGATACTGA AACAC-3' (FRAG.No: ) (SEQ. ID NO:2466) 5'-AGGATGATGG TGATGGGGAA CTAAATGGGG AAATATGGAA GGTCACAGGA AAAGTTAACA CAAGTTAGCA AAAAGTTAAC ATAACACAAA AAGGTCTTGC AGGAAAAAAA AAAGAAAAGA AAAGAAAGAA AAAGTCTCCA AGAATGGT GGACAGCCAA AATGAATACT TATAGTCACG TATACCTGCT CACTCCTGAC GCTTCACTCA 35 CACACAGCAC AGGATCTGGT GAGGCTATCA CTAAATGTGC CACAITGTGG TTAAGTTTA CCTGATTAAC GAAATGCTCA CACTTCTAAA CTGAGGTCCT TACAGTAGAT TCCTTTTGCA AGATTGTTAC TGGCTTACAA CTTAAAAATA AAGGAAAATC ACAAGGAAAG AAAAGTGGGG AAAAAATCGG AGGAAACTTG CCCCTGCCCT GGCCACCGGC AAGGCTGCCA CAAAGGGGTT AAAAGTTAAG TGGAAGTGGA GCTTGAAGAA GTGGGATGGG GCCTCTCCAG GAAAGCTGAA CGAGGCATCT GGAGCCCGAA CAAACCTCCA CCTTTTTTGG CCTCGACGGC 40 GGCAACCCAG CCTCCCTCCT AACGCCCTCC GCCTTTGGGA CCAACCAGGG GAGCTCAAGT TAGTAGCAGC CAAGGAGAGG CGCTGCCTTG CCAAGACTAA AAAGGGAGGG GAGAAGAGAG GAAAAAAGCA AGAATCCCCC ACCCCTCTCC CGGGCGGAGG GGGCGGGAAG AGCGCGTCCT GGCCAAGCCG AGTAGTGTCT TCCACTCGGT GCGTCTCTCT AGGAGCCGCG CGGGAAGGAT GCTGGTCCGC AGGGGCGCGC GCGCAGGGCC CAGGATGCCG CGGGGCTGGA CCGCGCTTTG CTTGCTGAGT TTGCTGC-3' (FRAG. NO:_) (SEQ. ID NO:2464) 45 5'-CCTTTTTTGG CCTCGACGGC GGCAACCCAG CCTCCCTCCT AACGCCCTCC GCCTTTGGGA CCAACCAGGG GAGCTCAAGT TAGTAGCAGC CAAGGAGAGG CGCTGCCTTG CCAAGACTAA AAAGGGAGGG GAGAAGAGAG GAAAAAAGCA AGAATCCCCC ACCCCTCTCC CGGGCGGAGG GGGCGGGAAG AGCGCGTCCT GGCCAAGCCG AGTAGTGTCT TCCACTCGGT GCGTCTCTCT AGGAGCCGCG CGGGAAGGAT GCTGGTCCGC AGGGGCGCGC GCGAGGGCCC AGGATGCCGC GGGGCTGGAC CGCGCTTTGC TTGCTGAGTT TGCTGCCTTC TGGGTTCATG 50 AGTCTTGACA ACAACGGTAC TGCTACCCCA GAGTTACCTA CCCAGGGAAC ATTTCAAAT GTTTCTACAA ATGTATCCTA CCAAGAAACT ACAACACCTA GTACCCTTGG AAGTACCAGC CTGCACCCTG TGTCTCAACA TGGCAATGAG GCCACAACAA ACATCACAGA AACGACAGTC AAATTCACAT CTACCTCTGT GATAACCTCA GTTTATGGAA ACACAAACTC TTCTGTCCAG TCACAGACCT CTGTAATCAG CACAGTGTTC ACCACCCCAG CCAACGTTTC AACTCCAGAG ACAACCTTGA AGCCTAGCCT GTCACCTGGA AATGTTTCAG ACCTTTCAAC 55 CACTAGCACT AGCCTTGCAA CATCTCCCAC TAAACCCTAT ACATCATCTT CTCCTATCCT AAGTGACATC AAGGCAGAAA TCAAATGTTC AGGCATCAGA GAAGTGAAAT TGACTCAGGG CATCTGCCTG GAGCAAAATA AGACCTCCAG CTGTGCGGAG TTTAAGAAGG ACAGGGGAGA GGGCCTGGCC CGAGTGCTGT GTGGGGAGGA GCAGGCTGAT GCTGATGCTG GGGCCCAGGT ATGCTCCCTG CTCCTTGCCC AGTCTGAGGT GAGGCCTCAG TGTCTACTGC TGGTCTTGGC CAACAGAACA GAAATTTCCA GCAAACTCCA ACTTATGAAA AAGCACCAAT 60 CTGACCTGAA AAAGCTGGGG ATCCTAGATT TCACTGAGCA AGATGTrGCA AGCCACCAGA GCTATTCCCA AAAGACCCTG ATTGCACTGG TCACCTCGGG AGCCCTGCTG GCTGTCTTGG GCATCACTGG CTATTTCCTG ATGAATCGCC GCAGCTGGAG CCCCACAGGA GAAAGGCTGG GCGAAGACCC TTATTACACG GAAAACGGTG GAGGCCAGGG CTATAGCTCA GGACCTGGGA CCTCCCCTGA GGCTCAGGGA AAGGCCAGTG TGAACCGAGG GGCTCAGAAA AACGGGACCG GCCAGGCCAC CTCCAGAAAC GGCCATTCAG CAAGACAACA CGTGGTGGCT 65 GATACCGAAT TGTGACTCGG CTAGGTGGGG CAAGGCTGGG CAGTGTCCGA GAGAGCACCC CTCTCTGCAT CTGACCACGT GCTACCCCCA TGCTGGAGGT GACATCTCTT ACGCCCAACC CTTCCCCACT GCACACACCT CAGAGGCTGT TCTTGGGGCC CTACACCTTG AGGAGGGGGC AGGTAAACTC CTGTCCTTTA CACAT7CGGC TCCCTGGAGC CAGACTCTGG TCTTCTTTGG GTAAACGTGT GACGGGGGAA AGCCAAGGTC TGGAGAAGCT CCCAGGAACA ATCGATGGCC TTGCAGCACT CACACAGGAC CCCCTTCCCC TACCCCCTCC TCTCTGCCGC WO 00/62736 PCT/USOO/08020 293 AATACAGGAA CCCCCAGGGG AAAGATGAGC TTTCTAGGC TACAATTTTC TCCCAGGAAG CTGATTTT TACCGTTTCT TCCCTGTATT TTCTTCTCT ACTTTGAGGA AACCAAAGTA ACCTTGCA CCTGCTCTCT TGTAATGATA TAGCCAGAAA AACGTGTTGC CTTGAACCAC TTCCCTCATC TCTCCTCCAA GACACTGTGG ACTTGGTCAC CAGCTCCTCC CTTGTTCTCT AAGTTCCACT GAGCTCCATG TGCCCCCTCT ACCATTTGCA 5 GAGTCCTGCA CAGTTTCTG GCTGGAGCCT AGAACAGGCC TCCCAAGTTT TAGGACAAAC AGCTCAGTTC TAGTCTCTCT GGGGCCACAC AGAAACTCTT TTGGGCTCC TTTTCTCCC TCTGGATCAA AGTAGGCAGG ACCATGGGAC CAGGTCTTGG AGCTGAGCCT CTCACCTGTA CTCTTCCGAA AAATCCTCTT CCTCTGAGGC TGGATCCTAG CCTTATCCTC TGATCTCCAT GGCTTCCTCC TCCCTCCTGC CGACTCCTGG GTTGAGCTGT TGCCTCAGTC CCCCAACAGA TGCTTTCTG TCTCTGCCTC CCTCACCCTG AGCCCCTTCC TTGCTCTGCA 10 CCCCCATATG GTCATAGCCC AGATCAGCTC CTAACCCTTA TCACCAGCTG CCTCTTCTGT GGGTGACCCA GGTCCT'TGTT TGCTGTTGAT TTCTTCCAG AGGGGTTGAG CAGGGATCCT GGTTrCAATG ACGGTTGGAA ATAGAAAT CCAGAGAAGA GAGTATTGGG TAGATATTT TTCTGAATAC AAAGTGATGT GTAAATAC TGCAATTAAA GTGATACTGA AACAC-3' (FRAG. No:_) (SEQ. ID NO:2465) Eotaxin Antisense Nucleic Acids and Oligonucleotide Fragments 15 5'-GCATT-TTC AAGTTTTATG ATTTATTTAA CTTGTGGAAC AAAAATAAAC CAGAAACCAC CACCTCTCAC GCCAAAGCTC ACACCTTCAG CCTCCAACAT GAAGGTCTCC GCAGCACTTC TGTGGCTGCT GCTCATAGCA GCTGCCTTCA GCCCCCAGGG GCTCGCTGGG CCAGCTTCTG TCCCAACCAC CTGCTGC'T AACCTGGCCA ATAGGAAGAT ACCCCTTCAG CGACTAGAGA GCTACAGGAG AATCACCAGT GGCAAATGTC CCCAGAAAGC TGTGATCTTC AAGACCAAAC TGGCCAAGGA TATCTGTGCC GACCCCAAGA AGAAGTGGGT GCAGGATTCC 20 ATGAAGTATC TGGACCAAAA ATCTCCAACT CCAAAGCCAT AAATAATCAC CATITTGAA ACCAAACCAG AGCCTGAGTG TTGCCTAATT TGTTTTCCCT TCTTACAATG CATTCTGAGG TAACCTCATT ATCAGTCCAA AGGGCATGGG ITTATTATA TATATATATA TI1TITITT AAAAAAAAAC GTATTGCATT TAATTTATTG AGGCTT7AAA ACTTATCCTC CATGAATATC AGTTATTT AAACTGTAAA GCTTTGTGCA GATTCTITAC CCCCTGGGAG CCCCAATTCG ATCCCCTGTC ACGTGTGGGC AATGTTCCCC CTCTCCTCTC TTCCTCCCTG 25 GAATCTTGTA AAGGTCCTGG CAAAGATGAT CAGTATGAAA ATGTCATTGT TCTTGTGAAC CCAAAGTGTG ACTCATTAAA TGGAAGTAAA TGTrGITTA GGAATAC ATGAAGGTCT CCGCAGCACT TCTGTGGCTG CTGCTCATAG CAGCTGCCTT CAGCCCCCAG GGGCTCGCTG GGCCAGCTTC TGTCCCAACC ACCTGCTGCT TTAACCTGGC CAATAGGAAG ATACCCCTTC AGCGACTAGA GAGCTACAGG AGAATCACCA GTGGCAAATG TCCCCAGAAA GCTGTGATCT TCAAGACCAA ACTGGCCAAG GATATCTGTG CCGACCCCAA GAAGAAGTGG 30 GTGCAGGATT CCATGAAGTA TCTGGACCAA AAATCTCCAA CTCCAAAGCC ATAA CCACATATTC CCCTCCTTTT CCAAGGCAAG ATCCAGATGG ATTAAAAAAT GTACCAAGTC CCTCCTACTA GCTTGCCTCT CTTCTGTTCT GCTTGACTTC CTAGGATCTG GAATCTGGTC AGCAATCAGG AATCCCTTCA TCGTGACCCC CGCATGGGCA AAGGCTTCCC TGGAATCTCC CACACTGTCT GCTCCCTATA AAAGGCAGGC AGATGGGCCA GAGGAGCAGA GAGGCTGAGA CCAACCCAGA AACCACCACC TCTCACGCCA AAGCTCACAC CTTCAGCCTC 35 CAACATGAAG GTCTCCGCAG CACTTCTGTG GCTGCTGCTC ATAGCAGCTG CCTTCAGCCC CCAGGGGCTC GCTGGGCCAG GTAAGCCCCC CAACTCCTTA CAGGAAAGGT AAGGTAACCA CCTCCAGGCT ACTAGGTCAG CAAGAATCTT TACAGACTCA CTGCAAATTC TCCATTTGAA AAATAGGGAA ACAGGTTTTG TGGGTGGACA AGAAATGCCT CAACCGTCAC ATCCAGTCAC TGGAAGAGCC AGAACTAGAA AGCTCCCGAG TCTTTTCCCC ACATTCAAGA GGGCCGCTGG GTGCATCCTT ACCCAGCTAT CCTTACAGTG TTGGGAATG GGGAATGGCT 40 CTGTCTTACT GTGGGCATGG TGGGCATT TGGCAGTGGG AGAGAAGGAA AATCTGT17GA TTAGAAGCTC AGTATGT'TAA TTCGACTCCA GGACAGCTTT CAGAGACAGT GGCTAAGAGA AGAACGAGGT CCCAGGGGAT CTCTTGAGGT GACTTATTTT GACACTCTTT GGGAAAGTTA TCTAGGAGAT TTGTTCCATA ACTCATTTTC CCATACTCTG GTGACAAATT TACTGAGTGT ATCGGTCCCA CTGAGCCAGT GCATAGCATG GTAACAAACA GTTCTAAATT ATCAATGACT TAACAGAATT AACTAAATTA ACAAAAGTTA CTTTCTCACT TGTACTAAAT 45 ATCTATAATG TATGGGCTCA GGCTTCTGCA TTTTATACTC AGGATTCTAG ACTGATGGAG AAGTTGCCAT GTGGGGGAAC ATTGATGGAT ACTGTGATAA AGCAGAAGAA AGCTCTCAGG AGTCTTGCAT AGGCAATGCA CTGTGGCTCA AAAATGACAC CCATCACTTT GTCTCCTTCT TTATTGATCA AAACTAATTA ATGCCTCCAA CCAAACAAAA GTGGCCAAGA AATGCAAGTC TACCTTGTGT CTCAAAACAG AGGATGGAGA ATATTGGTG AAAATTACCA TGACCATCAC ATGGCCACGT AGGTCTTTAT AATGACAGAG CTAGCATTTG TCACATTGAC 50 CAAGCTTTGT CCATACACTC TACAGTAATG ATGAGTCCTC AGTGCACAGG GGAGGATGCT GAAGACACAG GACAGCATCC TCCAGACACA TAAGACTTCA GAGCAGAGGG ATTCTCCCTC CACCTCTCGC AATTCCTTGC 'TTTCTCCTAA CTTCCTTTAC AAAGTCATGC TTGGAAATGT CTATGTATCA TCATGTGGCT CATTTI-TC TCTGTTCATT TTTTTTCCCC AAAATTCAGC TTCTGTCCCA ACCACCTGCT GC'ITTAACCT GGCCAATAGG AAGATACCCC TTCAGCGACT AGAGAGCTAC AGGAGAATCA CCAGTGGCAA ATGTCCCCAG AAAGCTGTGA 55 TGTAAGTAAA TAAAGTTCAC CCTCCCCTAG ACAAAAAAAT AATGTCTAGG GCACAGAGTC AAGAACTGTG GGAGTCATAG ACTCTGATAG TTTGACCTCT ATGGTCCAAT TCATTAAIT TCACAAGTGA GTGTTCACTC CCAGCTCCCT GCCTGGGAGA TTGCTGTAGT CATATCAATT TCTTCAAGTC AAGAGCAAAG ATGGTTTTAC TGGGCCTTTA AGAGCAGCAA CTAACCCAAG AGTCTCATCC TTCCTCCTCT CCGTAGCAAC CCTTTGTCCA GGGGCAGATG GTCCTTAAAT ATTTAGGGTC AAATGGGCAG AATT7CAAA AACAATCCTT CCAATTGCAT 60 CCTGATTCTC CCCACAGCTT CAAGACCAAA CTGGCCAAGG ATATCTGTGC CGACCCCAAG AAGAAGTGGG TGCAGGATTC CATGAAGTAT CTGGACCAAA AATCTCCAAC TCCAAAGCCA TAAATAATCA CCATTTTTGA AACCAAACCA GAGCCTGAGT GTTGCCTAAT TTGTTTTCCC TTCTTACAAT GCATTCTGAG GTAACCTCAT TATCAGTCCA AAGGGCATGG GITTATTAT ATATATATAT ATATATTT 1TTAAAAAA AAACGTATFG CATTTAATTT ATTGAGGCTT TAAAACTTAT CCTCCATGAA TATCAGTTAT TTAAACTG TAAAGCTTTG 65 TGCAGATTCT TTACCCCCTG GGAGCCCCAA TTCGATCCCC TGTCACGTGT GGGCAATGTT CCCCCTCTCC WO 00/62736 PCT/USOO/08020 294 TCTCTTCCTC CCTGGAATCT TGTAAAGGTC CTGGCAAAGA TGATCAGTAT GAAAATGTCA TTGTTCTTGT GAACCCAAAG TGTGACTCAT TAAATGGAAG TAATGTTGTT TTAGGAATAC ATAAAGTATG TGCATATT ATTATAGTCA CTAGTTGTAA 1TTT1GTG GGAAATCCAC ACTGAGCTGA GGGGG-3' (FRAG.NO:_) (SEQ. ID NO:2494) 5 5'-GCATTTTTTC AAGTTTTATG ATTTATTTAA CTTGTGGAAC AAAAATAAAC CAGAAACCAC CACCTCTCAC GCCAAAGCTC ACACCTTCAG CCTCCAACAT GAAGGTCTCC GCAGCACTTC. TGTGGCTGCT GCTCATAGCA GCTGCCTTCA GCCCCCAGGG GCTCGCTGGG CCAGCTTCTG TCCCAACCAC CTGCTGCT AACCTGGCCA ATAGGAAGAT ACCCCTTCAG CGACTAGAGA GCTACAGGAG AATCACCAGT GGCAAATGTC CCCAGAAAGC TGTGATCTTC AAGACCAAAC TGGCCAAGGA TATCTGTGCC GACCCCAAGA AGAAGTGGGT GCAGGATTCC 10 ATGAAGTATC TGGACCAAAA ATCTCCAACT CCAAAGCCAT AAATAATCAC CATTTGAA ACCAAACCAG AGCCTGAGTG TTGCCTAATT TGTTTCCCT TCTTACAATG CATTCTGAGG TAACCTCATT ATCAGTCCAA AGGGCATGGG TTTTATTATA TATATATATA TTITrITIT AAAAAAAAAC GTATTGCATT TAATTTATTG AGGCTTTAAA ACTTATCCTC CATGAATATC AGTTATTTT AAACTGTAAA GCTTTGTGCA GATTCTTTAC CCCCTGGGAG CCCCAATTCG ATCCCCTGTC ACGTGTGGGC AATGTTCCCC CTCTCCTCTC TTCCTCCCTG 15 GAATCTTGTA AAGGTCCTGG CAAAGATGAT CAGTATGAAA ATGTCATTGT TCTTGTGAAC CCAAAGTGTG ACTCA'TTAAA TGGAAGTAAA TGTTGTTTTA GGAATAC-3' (FRAG.NO:_) (SEQ. ID NO:2491) 5'-ATGAAGGTCT CCGCAGCACT TCTGTGGCTG CTGCTCATAG CAGCTGCC17 CAGCCCCCAG GGGCTCGCTG GGCCAGCTTC TGTCCCAACC ACCTGCTGCT TTAACCTGGC CAATAGGAAG ATACCCCTC AGCGACTAGA GAGCTACAGG AGAATCACCA GTGGCAAATG TCCCCAGAAA GCTGTGATCT TCAAGACCAA ACTGGCCAAG 20 GATATCTGTG CCGACCCCAA GAAGAAGTGG GTGCAGGATT CCATGAAGTA TCTGGACCAA AAATCTCCAA CTCCAAAGCC ATAA-3' (FRAG. NO:_) (SEQ. ID NO:2492) 5'-CCACATATTC CCCTCCTTTT CCAAGGCAAG ATCCAGATGG ATTAAAAAAT GTACCAAGTC CCTCCTACTA GCTTGCCTCT CTTCTGTTCT GCTTGACTTC CTAGGATCTG GAATCTGGTC AGCAATCAGG AATCCCTTCA TCGTGACCCC CGCATGGGCA AAGGCTTCCC TGGAATCTCC CACACTGTCT GCTCCCTATA AAAGGCAGGC 25 AGATGGGCCA GAGGAGCAGA GAGGCTGAGA CCAACCCAGA AACCACCACC TCTCACGCCA AAGCTCACAC CT'TCAGCCTC CAACATGAAG GTCTCCGCAG CACTTCTGTG GCTGCTGCTC ATAGCAGCTG CCTTCAGCCC CCAGGGGCTC GCTGGGCCAG GTAAGCCCCC CAACTCCTTA CAGGAAAGGT AAGGTAACCA CCTCCAGGCT ACTAGGTCAG CAAGAATCTT TACAGACTCA CTGCAAATTC TCCATTTGAA AAATAGGGAA ACAGGTTTTG TGGGTGGACA AGAAATGCCT CAACCGTCAC ATCCAGTCAC TGGAAGAGCC AGAACTAGAA AGCTCCCGAG 30 TCTTCCCC ACATTCAAGA GGGCCGCTGG GTGCATCCTT ACCCAGCTAT CCTTACAGTG TTTGGGAATG GGGAATGGCT CTGTCTTACT GTGGGCATGG TGGGCATT TGGCAGTGGG AGAGAAGGAA AATCTGTTGA TTAGAAGCTC AGTATGTTAA TTCGACTCCA GGACAGCTTT CAGAGACAGT GGCTAAGAGA AGAACGAGGT CCCAGGGGAT CTCTTGAGGT GACTTATT GACACTCTTT GGGAAAGTTA TCTAGGAGAT TTGTTCCATA ACTCATTTTC CCATACTCTG GTGACAAATT TACTGAGTGT ATCGGTCCCA CTGAGCCAGT GCATAGCATG 35 GTAACAAACA GTTCTAAATT ATCAATGACT TAACAGAATT AACTAAATTA ACAAAAGTTA CTTTCTCACT TGTACTAAAT ATCTATAATG TATGGGCTCA GGCTTCTGCA TTATACTC AGGATTCTAG ACTGATGGAG AAGTTGCCAT GTGGGGGAAC ATTGATGGAT ACTGTGATAA AGCAGAAGAA AGCTCTCAGG AGTCTGCAT AGGCAATGCA CTGTGGCTCA AAAATGACAC CCATCACTTT GTCTCCTTCT TTATTGATCA AAACTAATTA ATGCCTCCAA CCAAACAAAA GTGGCCAAGA AATGCAAGTC TACCTTGTGT CTCAAAACAG AGGATGGAGA 40 ATATTTGGTG AAAATTACCA TGACCATCAC ATGGCCACGT AGGTCTAT AATGACAGAG CTAGCATTTG TCACATTGAC CAAGCTT7GT CCATACACTC TACAGTAATG ATGAGTCCTC AGTGCACAGG GGAGGATGCT GAAGACACAG GACAGCATCC TCCAGACACA TAAGACTTCA GAGCAGAGGG ATTCTCCCTC CACCTCTCGC AATTCCTTGC TTTCTCCTAA CTTCCTTTAC AAAGTCATGC TTGGAAATGT CTATGTATCA TCATGTGGCT CATTTTTC TCTGTTCATT T TTTCCCC AAAATTCAGC TTCTGTCCCA ACCACCTGCT GCTTTAACCT 45 GGCCAATAGG AAGATACCCC TTCAGCGACT AGAGAGCTAC AGGAGAATCA CCAGTGGCAA ATGTCCCCAG AAAGCTGTGA TGTAAGTAAA TAAAGTTCAC CCTCCCCTAG ACAAAAAAAT AATGTCTAGG GCACAGAGTC AAGAACTGTG GGAGTCATAG ACTCTGATAG TTTGACCTCT ATGGTCCAAT TCATTAAT TCACAAGTGA GTGTTCACTC CCAGCTCCCT GCCTGGGAGA TTGCTGTAGT CATATCAATT TCTTCAAGTC AAGAGCAAAG ATGGTTTTAC TGGGCCTTTA AGAGCAGCAA CTAACCCAAG AGTCTCATCC TICCTCCTCT CCGTAGCAAC 50 CCTTTGTCCA GGGGCAGATG GTCCTTAAAT ATTTAGGGTC AAATGGGCAG AATTTTCAAA AACAATCCTT CCAATTGCAT CCTGATTCTC CCCACAGCTT CAAGACCAAA CTGGCCAAGG ATATCTGTGC CGACCCCAAG AAGAAGTGGG TGCAGGATTC CATGAAGTAT CTGGACCAAA AATCTCCAAC TCCAAAGCCA TAAATAATCA CCATTTGA AACCAAACCA GAGCCTGAGT GTTGCCTAAT TTGTITTCCC TTCTTACAAT GCATTCTGAG GTAACCTCAT TATCAGTCCA AAGGGCATGG GTTATTAT ATATATATAT ATATATT TTTTAAAAAA 55 AAACGTATTG CATTTAATTT ATTGAGGCTT TAAAACTTAT CCTCCATGAA TATCAGTTAT TTTTAAACTG TAAAGCTTTG TGCAGATTCT TTACCCCCTG GGAGCCCCAA TTCGATCCCC TGTCACGTGT GGGCAATGTT CCCCCTCTCC TCTCTTCCTC CCTGGAATCT TGTAAAGGTC CTGGCAAAGA TGATCAGTAT GAAAATGTCA TTGTTCTTGT GAACCCAAAG TGTGACTCAT TAAATGGAAG TAATGTTGTT TTAGGAATAC ATAAAGTATG TGCATATTTT ATTATAGTCA CTAGTTGTAA TTITTGTG GGAAATCCAC ACTGAGCTGA GGGGG-3' 60 (FRAG.NO:_) (SEQ. ID NO:2493) FK-506 Binding Protein Nucleic Acids and Oligonucleotide Fragments 5'- GCCAGGTCGC TGTTGGTCCA CGCCGCCCGT CGCGCCGCCC GCCCGCTCAG CGTCCGCCGC CGCCATGGGA GGCCGGAGCC GAGCCGGGGT CGGGCAGCAG CAGGGACCCC CCAGAGGCGG GGCCTGTGGG ACCGCTATGG GCGTGGAGAT CGAGACCATC TCCCCCGGAG ACGGAAGGAC ATTCCCCAAG AAGGGCCAAA CGTGTGTGGT 65 GCACTACACA GGAATGCTCC AAAATGGGAA GAAGTTTGAT TCATCCAGAG ACAGAAACAA ACCTTTCAAG WO 00/62736 PCT/USOO/08020 295 TTCAGAATTG GCAAACAGGA AGTCATCAAA GGTTGAAG AGGGTGCAGC CCAGATGAGC TTGGGGCAGA GGGCGAAGCT GACCTGCACC CCTGATGTGG CATATGGAGC CACGGGCCAC CCCGGTGTCA TCCCTCCCAA TGCCACCCTC ATCTTTGACG TGGAGCTGCT CAACTTAGAG TGAAGGCAGG AAGGAACTCA AGGTGGCTGG AGATGGCTGC TGCTCACCCT CCTAGCCTGC TCTGCCACTG GGACGGCTCC TGCTTTTGGG GCTCTTGATC 5 AGTGTGCTAA CCTCACTGCC TCATGGCATC ATCCATrCTC TCTGCCCAAG TTGCTCTGTA TGTGTTCGTC AGTGTTCATG CGAATTCTTG CTTGAGGAAA CTTCGGTTGC AGATTGAAGC ATCAGGTT GTGCAFTG TGTGATGCAT GTAGTAGCCT TTCCTGATGA CAGAACACAG ATCTCTTGTT CGCACAATCT ACACTGCCTT ACCTTCACTT AAACCACACA CACAAGGTGC TCAGACATGA AATGTACATG GCGTACCGTA CACAGAGGGA CTTGAGCCAG TTACCTTTGC TGTCACTTTC TCTCTTATAA ATTCTGTTAG CTGCTCACTT AAACAATGTC 10 CTCTTTGAGA AAATGTAAAA TAAAGGCTCT GTGCTTGACA GAATTCGGGC CGCCGCCAGG TCGCTGTrGG TCCACGCCGC CCGTCGCGCC GCCCGCCCGC TCAGCGTCCG CCGCCGCCAT GGGAGTGCAG GTGGAAACCA TCTCCCCAGG AGACGGGCGC ACCTTCCCCA AGCGCGGCCA GACCTGCGTG GTGCACTACA CCGGGATGCT TGAAGATGGA AAGAAATTTG ATTCCTCCCG GGACAGAAAC AAGCCCTTA AGTTTATGCT AGGCAAGCAG GAGGTGATCC GAGGCTGGGA AGAAGGGGTT GCCCAGATGA GTGTGGGTCA GAGAGCCAAA CTGACTATAT 15 CTCCAGATTA TGCCTATGGT GCCACTGGGC ACCCAGGCAT CATCCCACCA CATGCCACTC TCGTCTTCGA TGTGGAGCTT CTAAAACTGG AATGACAGGA ATGGCCTCCT CCCTTAGCTC CCTGTTCTTG GATCTGCCAT GGAGGGATCT GGTGCCTCCA GACATGTGCA CATGAGTCCA TATGGAGCTT TTCCTGATGT TCCACTCCAC TTrGTATAGA CATCTGCCCT GACTGAATGT GTTCTGTCAC TCAGCTGC 17CCGACACC TCTGTTTCCT CTTCCCCTTT CTCCTCGTAT GTGTGTTTAC CTAAACTATA TGCCATAAAC CTCAAGTTAT TCATTTATT 20 TTGTTTTCAT TTTGGGGTGA AGATTCAGTT TCAGTCTTTT GGATATAGGT TTCCAATTAA GTACATGGTC AAGTATTAAC AGCACAAGTG GTAGGTTAAC ATTAGAATAG GAATTGGTGT TGGGGGGGGG GTTTGCAAGA ATATTTTATT TTAATTfTT GGATGAAATT TTTATCTATT ATATATTAAA CATTCTTGCT GCTGCGCTGC AAAGCCATAG CAGATTTGAG GCGCTGTTGA GGACTGAATT ACTCTCCAAG TTGAGAGATG TCTTTGGGTT AAATTAAAAG CCCTACCTAA AACTGAGGTG GGGATGGGGA GAGCCTTTGC CTCCACCATT CCCACCCACC 25 CTCCCCTTAA ACCCTCTGCC TTTGAAAGTA GATCATGTTC ACTGCAATGC TGGACACTAC AGGTATCTGT CCCTGGGCCA GCAGGGACCT CTGAAGCCTT CTTTGTGGCC TTTTTT TTCATCCTGT GGTTTTTCTA ATGGACTTTC AGGAATTTTG TAATCTCATA ACTTTCCAAG CTCCACCACT TCCTAAATCT TAAGAACTT AATTGACAGT TTCAATTGAA GGTGCTGT GTAGACTTAA CACCCAGTGA AAGCCCAGCC ATCATGACAA ATCCTTGAAT GTTCTCTTAA GAAAATGATG CTGGTCATCG CAGCTTCAGC ATCTCCTGTT TTTTGATGCT 30 TGGCTCCCTC TGCTGATCTC AGTTTCCTGG CTCCTCC CTCAGCCCCT TCTCACCCCT TTGCTGTCCT GTGTAGTGAT TTGGTGAGAA ATCGTTGCTG CACCCTTCCC CCAGCACCAT TTATGAGTCT CAAGTTAT TATTGCAATA AAAGTGCTTT ATGCCCGAAT TC GCCGCCGCCA TGGGAGTGCA GGTGGAAACC ATCTCCCCAG GAGACGGGCG CACCTTCCCC AAGCGCGGCC AGACCTGCGT GGTGCACTAC ACCGGGATGC TTGAAGATGG AAAGAAATTT GATTCCTCCC GGGACAGAAA CAAGCCCTTT AAGTTTATGC TAGGCAAGCA 35 GGAGGTGATC CGAGGCTGGG AAGAAGGGGT TGCCCAGATG AGTGTGGGTC AGAGAGCCAA ACTGACTATA TCTCCAGATT ATGCCTATGG TGCCACTGGG CACCCAGGCA TCATCCCACC ACATGCCACT CTCGTCTTCG ATGTGGAGCT TCTAAAACTG GAATGACAGG AATGGCCTCC TCCCTTAGCT CCCTGTTCTT GGATCTGCCR TGGAGGGATC TGGTGCCTCC AGACATGTGC ACATGARTCC ATATGGAGCT TTTCCTGATG TTCCACTCCA C'TTTGTATAG ACATCTGCCC TGACTGAATG TGTTCTGTCA CTCAGCTG CTTCCGACAC CTCTGTTTCC 40 TCTTCCCCTT TCTCCTCGTA TGTGTGTA CCTAAACTAT ATGCCATAAA CCTCAAGTTA TrCA-3' (FRAG.NO:_) (SEQ. ID NO:2499) 5'- GCCAGGTCGC TGTTGGTCCA CGCCGCCCGT CGCGCCGCCC GCCCGCTCAG CGTCCGCCGC CGCCATGGGA 3' (FRAG. No:_)(SEQ. ID NO: 2495) 5'-GGCCGGAGCC GAGCCGGGGT CGGGCAGCAG CAGGGACCCC CCAGAGGCGG GGCCTGTGGG CCGCTATGG 45 GCGTGGAGAT CGAGACCATC TCCCCCGGAG ACGGAAGGAC ATTCCCCAAG AAGGGCCAAA CGTGTGTGGT GCACTACACA GGAATGCTCC AAAATGGGAA GAAGTTTGAT TCATCCAGAG ACAGAAACAA ACCTTTCAAG TTCAGAATTG GCAAACAGGA AGTCATCAAA GGTTTTGAAG AGGGTGCAGC CCAGATGAGC TTGGGGCAGA GGGCGAAGCT GACCTGCACC CCTGATGTGG CATATGGAGC CACGGGCCAC CCCGGTGTCA TCCCTCCCAA TGCCACCCTC ATCTTTGACG TGGAGCTGCT CAACTTAGAG TGAAGGCAGG AAGGAACTCA AGGTGGCTGG 50 AGATGGCTGC TGCTCACCCT CCTAGCCTGC TCTGCCACTG GGACGGCTCC TGCTTTTGGG GCTCTITGATC AGTGTGCTAA CCTCACTGCC TCATGGCATC ATCCATTCTC TCTGCCCAAG TTGCTCTGTA TGTGTTCGTC AGTGTTCATG CGAATTCTTG CTTGAGGAAA CTTCGGTTGC AGATTGAAGC ATTTCAGGTT GTGCATTG TGTGATGCAT GTAGTAGCCT TTCCTGATGA CAGAACACAG ATCTCTTGTT CGCACAATCT ACACTGCCTT ACCTTCACTT AAACCACACA CACAAGGTGC TCAGACATGA AATGTACATG GCGTACCGTA CACAGAGGGA 55 CTTGAGCCAG TTACCTTTGC TGTCACTTTC TCTCTTATAA ATTCTGTFAG CTGCTCACTI AAACAATGTC CTCTTTGAGA AAATGTAAAA TAAAGGCTCT GTGCTTGACA-3' (FRAG. NO:j (SEQ. ID NO:2496) 5'-GAATTCGGGC CGCCGCCAGG TCGCTGTTGG TCCACGCCGC CCGTCGCGCC GCCCGCCCGC TCAGCGTCCG CCGCCGCCAT GGGAGTGCAG GTGGAAACCA TCTCCCCAGG AGACGGGCGC ACCTTCCCCA AGCGCGGCCA GACCTGCGTG GTGCACTACA CCGGGATGCT TGAAGATGGA AAGAAATTTG ATTCCTCCCG GGACAGAAAC 60 AAGCCCTTTA AGTTTATGCT AGGCAAGCAG GAGGTGATCC GAGGCTGGGA AGAAGGGGTT GCCCAGATGA GTGTGGGTCA GAGAGCCAAA CTGACTATAT CTCCAGATTA TGCCTATGGT GCCACTGGGC ACCCAGGCAT CATCCCACCA CATGCCACTC TCGTCTrCGA TGTGGAGCTT CTAAAACTGG AATGACAGGA ATGGCCTCCT CCCTTAGCTC CCTGTTCTTG GATCTGCCAT GGAGGGATCT GGTGCCTCCA GACATGTGCA CATGAGTCCA TATGGAGCTT TTCCTGATGT TCCACTCCAC TTTGTATAGA CATCTGCCCT GACTGAATGT GTTCTGTCAC 65 TCAGCTTTGC TTCCGACACC TCTGTTTCCT CTTCCCCTTT CTCCTCGTAT GTGTGTTTAC CTAAACTATA TGCCATAAAC CTCAAGTTAT TCATTATT TTGTTTCAT TTTGGGGTGA AGATTCAGTT TCAGTCTTT WO 00/62736 PCT/USOO/08020 296 GGATATAGGT TTCCAATTAA GTACATGGTC AAGTATTAAC AGCACAAGTG GTAGGTTAAC ATTAGAATAG GAATTGGTGT TGGGGGGGGG GTTTGCAAGA ATATITTATT TTAATTTTTT GGATGAAATT TTTATCTATT ATATATTAAA CATTCTTGCT GCTGCGCTGC AAAGCCATAG CAGATTTGAG GCGCTGTTGA GGACTGAATT ACTCTCCAAG TTGAGAGATG TCTGGGTT AAATTAAAAG CCCTACCTAA AACTGAGGTG GGGATGGGGA 5 GAGCCTTTGC CTCCACCATT CCCACCCACC CTCCCCTTAA ACCCTCTGCC TTTGAAAGTA GATCATGTTC ACTGCAATGC TGGACACTAC AGGTATCTGT CCCTGGGCCA GCAGGGACCT CTGAAGCCTT CTTTGTGGCC TTTTTT=TT TTCATCCTGT GGTTTTTCTA ATGGACTTTC AGGAATTTTG TAATCTCATA ACTTTCCAAG CTCCACCACT TCCTAAATCT TAAGAAC'T AATTGACAGT TTCAATTGAA GGTGCTGTTT GTAGACTTAA CACCCAGTGA AAGCCCAGCC ATCATGACAA ATCCTTGAAT GTTCTCTTAA GAAAATGATG CTGGTCATCG 10 CAGCTTCAGC ATCTCCTGTT ITTGATGCT TGGCTCCCTC TGCTGATCTC AGTTTCCTGG CTTTTCCTCC CTCAGCCCCT TCTCACCCCT TTGCTGTCCT GTGTAGTGAT TTGGTGAGAA ATCGTTGCTG CACCCTTCCC CCAGCACCAT TTATGAGTCT CAAGTTTTAT TATFGCAATA AAAGTGCTTT ATGCCCGAAT TC-3' (FRAG.NO: ) (SEQ. ID NO:2497) 5' GCCGCCGCCA TGGGAGTGCA GGTGGAAACC ATCTCCCCAG GAGACGGGCG CACCTTCCCC AAGCGCGGCC 15 AGACCTGCGT GGTGCACTAC ACCGGGATGC TTGAAGATGG AAAGAAATTT GATTCCTCCC GGGACAGAAA CAAGCCCTTT AAGTTTATGC TAGGCAAGCA GGAGGTGATC CGAGGCTGGG AAGAAGGGGT TGCCCAGATG AGTGTGGGTC AGAGAGCCAA ACTGACTATA TCTCCAGATT ATGCCTATGG TGCCACTGGG CACCCAGGCA TCATCCCACC ACATGCCACT CTCGTCTTCG ATGTGGAGCT TCTAAAACTG GAATGACAGG AATGGCCTCC TCCCTTAGCT CCCTGTTCTT GGATCTGCCR TGGAGGGATC TGGTGCCTCC AGACATGTGC ACATGARTCC 20 ATATGGAGCT TTTCCTGATG TTCCACTCCA CTTTGTATAG ACATCTGCCC TGACTGAATG TGTTCTGTCA CTCAGCTTTG CTTCCGACAC CTCTGTTTCC TCTTCCCCTT TCTCCTCGTA TGTGTGTTTA CCTAAACTAT ATGCCATAAA CCTCAAGTTA TTCA-3' (FRAG. NO:_) (SEQ. ID NO:2498) wherein B is adenosine, or, more preferably, replaces adenosine and is an "equivame\\lent" or a "universal" base, and adenosine A 2 a receptor agonist or only minimally antagonist, an adenosine A 2 25 receptor antagonist, an adenosine A 3 receptor antagonist, or an adenosine A, receptor antagonist. Similarly, adenosine (A) may always be replaced by an "alternative", "equivalent" and/or "universal" base having a small fraction, preferably less than 0.3 of the activity of adenosine at the adenosine receptor(s), as described above. In one preferred embodiment, the links between neighboring mononucleotides are 30 phosphodiester links. In another preferred, at least one mononucleotide phosphodiester residue of the anti-sense oligonucleotide(s) is substituted by a methylphosphonate, phosphotriester, phosphorothioate, phosphorodithioate, boranophosphate, formacetal, thioformacetal, thioether, carbonate, carbamate, sulfate, sulfonate, sulfamate, sulfonamide, sulfone, sulfite, sulfoxide, sulfide, hydroxylamine, 2'-0 methyl, methylene(methyimino), methyleneoxy (methylimino), phosphoramidate residues, and 35 combinations thereof. The oligos having one or more phosphodiester residues substituted by one or more of the other residues are generally longer lasting, given that these residues are more resistant to hydrolysis than the phosphodiester residue. In some cases up to about 10%, about 30%, about 50%, about 75%, and even all phosphodiester residues may be substituted (100%). Typically, the multiple target anti-sense oligonucleotide (oligo) of the invention comprises at least about 7 mononucleotides, 40 in some instances up to 60 and more mononucleotides, preferably about 10 to about 36, and more preferably about 12 to about 21 mononucleotides. However, other lengths are also suitable depending on the length of the target macromolecule. Examples of the MTA oligos of the invention are provided in Table 3 below, which includes ninety-four sequences (SEQ ID NOS.: 2316 through 2410). Table 3: MTA Oligos, Location Targeted & Target 45 MTA Oligo SEQ. ID Location Compound Target No. Targeted HUMNFKBP65A AS CCC GGC CCC GCC TCG TGC C 3019 5'=1 EPI 2192 CGT CCB TGC CGC GGG CCC 3020 5'=28(AUG)EPI 2193 50 GCC CCG CTG CTT GGG CTG CTC TGC CGG G 3021 5'=65 EPI 2194 TCT GTG CTC CTC TCG CCT GGG 3022 5'=137 EPI 2195 TGG TGG GGT GGG TCT TGG TGG 3023 5'=159 . EPI 2196 CTG TCC CTG GTC CTG TG 3024 5'=196 EPI 2197 GGT CCC GCT TCT TC 3025 5'=362 EPI 2198 55 GGG GTT GTT GTT GGT CTG G 3026 5'=401 EPI 2199 TGT CCT CTT TCT GC 3026 5'=656 EPI 2200 GCC TCG GGC CTC CC 3027 5'=697 EPI 2201 GGC TGG GGT CTG CGT 3028 5'=769 EPI 2202 WO 00/62736 PCT/US00/08020 297 GGC CGG GGG TCG GTG GGT CCG CTG 3029 5'=953 EPI 2203 GGG CTG GGG TGC TGG CTT GGG G 3030 5'=1022 EPI 2204 GGG GCT GGG GCC TGG GCC 3031 5'=1208 EPI 2205 GCC TGG GTG GGC TTG GGG GC 3032 5'=1272 EPI 2206 5 GCT GGG TCT GTG CTG TTG CC 3033 5'=1362 EPI 2207 GTT GTG TGG GGG GCC 3034 5'= 1451 EPI 2208 GCT GGG TCG GGG GGC CTC TGG GCT GTC 3035 5'=1511 EPI 2209 GCC CCG GGG CCC CC 3036 5'=1550 EPI 2210 TGG CTC CCC CCT CC 3037 5'=1772 EPI 2211 10 GCT CCC CCC TTT CC 3038 5'=1863 EPI 2212 CGG ACG AAG ACA GAG A 3039 5'=1979 EPI 2213 GGC TTT GTG GGC TC 3040 5'=2011 EPI 2214 GCC TGC TCT CCC CC 3041 5'=2312 EPI 2215 CCC GGC CCC GCC BCG BBC C 3042 intron EPI 2192-01A HSU50136C4Synth 15 CCC GGC CCC GCC BCG 3043 intron EPI 2192-01B CCC GGC CCC GCC BCG BBC C 3044 5'untr EPI 2192-02A HUMLIPOX5LO CCC GGC CCC GCC BCG 3045 5'untr EPI 2192-02B CCC GBC CCC GCC TCB BG 3046 trans EPI 2192-03A HSNFKBS Subunit CCC GBC CCC GCC TC 3047 trans EPI 2192-03B 20 CCG GCC CCG CCT C 3048 5'untr EPI 2192-04 TGFPR1 CCC GBB CCC GCB TBG TGC C 3049 5'trans EPI 2192-05A HSU58198Il enhan CCC GCB TBG TGC C 3050 5'untr EPI 2192-05B CCC GGB CCC BCC BBG TGC C 3051 3'trans EPI 2192-06 HSVECAD CBG BBC CCG CCT CGT GCC 3052 intron EPI 2192-07A NFKB2 25 C CCG CCT CGT GCC 3053 intron EPI 2192-07B NFKB2 CCG GCB CCG CCT CBT GCC 3054 5'trans EPI 2192-08 Carboxypep CCG GCC CCG CCB CBT GCC 3055 3'trans EPI 2192-09 HumADRA2C:2AdrKid CCC GBC CCC GBC TCG 3056 5'untrs EPI 2192-10 HUMFK506B CCC GGC CBC GBC TCG 3057 5'untrs EPI 2192-11 HSNBARKS10AdrKin 30 CCC GGC CCB GCC TBG 3058 5'UTR EPI 2192-12 HSNFXN1(NFKB1) CCC GGC BCB GBC TCG TBC C 3059 3'UTR EPI 2192-13 HSILF(transcrp. Factor ILF) CCC GGC CCC GCC BCG 3060 EPI-2192-14 NFKB/C4Syn/5-LO/ TGFBrec1 MTA 35 CCC GGC CCC GCC BCG 3061 EPI-2192-15NFKB/C4Syn/5-LOMTA TCC BTG CCG CGG GC 3062 3' trans EPI-2193-01 METOncogene TCC BTG CCB CGG GCC 3063 3' trans EPI-2193-02 HSFGR2(IG) TCC BTG CCB CGG GCC 3064 mid cod EPI-2193-03 5-LO TCC BTG CCB CBG GCC 3065 mid cod EPI-2193-04 HUMTK14 40 GTC CBT GBC GCG G 3066 3'trans EPI-2193-05 HUMTNFR TC CBT GBC GCG GG 3067 AUG Probl.HUMPTCH cardiacK+channel TCT GBG CTC CTC TBB CCT GGG 3068 intr EPI-2195-01 humCSPAcytotox. Ser. Protease 45 CTG TGC BCC TBB CBC CTG GG 3069 intr EPI-2195-02 HSINOSX08induc.NOS TGT GBT CCB CTB GBC TGG G 3070 EPI-2195-03 HUMACHRM2musc.m2 acetylch.rec. TCT GTB CTC BBC TCB CCT G 3071 EPI-2195-04 s86371s1 Neurokinin3Recept 50 TGC TCC TCB CBB CTG GG 3072 EPI-2195-05 HUMMIP1 Amacro inflam.factor WO 00/62736 PCT/USOO/08020 298 Table 3: MTA Oligos, Location Targeted & Target (Cont'd) MTA Oligo SEQ. ID Location Compound Target No. Targeted CTC CTC TBG CCT GG 3073 EPI-2195-06 HSNBARKS4 5 P-Adr Rec Kinase GTG CTC CBB TCB BCT GGG 3074 EPI-2195-07 HSTNFR2SO6TNF R2 GTG CBC CBB TCB CCT GGG 3075 EPI-2195-08 humfkbp fk506 binding prot. TCT GTG CBC CTC TBG BCT 3076 exon EPI-2195-09 HSNBARKS10-Adr. 10 Recept.Kinase CTG TBB TCC TBB CBC CTG G 3077 intron EPI-2195-10 HUMIL8 TGT GCT BBT CBC BCB TGG G 3078 EPI-2195-11 HSU50157 PDE4 GTG CBC CBC TCB CCT G 3079 intron/exon EPI-2195-12 IL-2 R CTG TGC BCC TCT C 3080 3'UTR EPI-2203-05 IL-6 R HSIL6R 15 CBG TGC BCC BCT CBC CTG 3081 intr/ex EPI-2203-06A HSIL2rG6 G TGC BCC BCT CBC CTG 3082 intr/ex EPI-2203-06B HSIL2rG6 CBC CTC TCB CCT GGG 3083 coding EPI-2203-07A HUMIL71 C CTC TCB CCT GGG 3084 coding EPI-2203-07B IL-7 HUMIL71 GCT CCB CTC GCC T 3085 coding EPI-2203-08 IL-6 R HSI6REC 20 TGC TCC TCB CGC C 3086 intron PDGF A EPI-2303-09 Chain HUMPDGFAB GTT GTT GBT CTG G 3087 3'utr EPI-2199-01 GATA-4Transcrip. Factor for IL-5 GGT TGB BBT TGG TCT TGG 3088 Coding EPI-2199-02 TNFa HUMTNFA GGT TGT TGB TGB TCT G 3089 Far 5'UTR EPI-2199-03 HSSUBPlG(Sub Pr) 25 GGG TTB BBG TTG BTC TGG 3090 Coding EPI-2199-04 NeutrophilAdh. R HUMNARIA GGG TTB BBG TTG BTC TGG 3091 HSHM2 EPI-2199-05 m2 Muscarinic R TTG TTG TBG BTC TGG 3092 HUMLlCAM EPI-2199-06 Li LeukAadhProt GGG TBG BBG BGT CCG CTG 3093 coding EPI-2203-01 HUMGATA2A 30 GGG TCB GBG GBT CBG CTG 3094 S71424S2 EPI-2203-02 IGE eps GGG TBG GTG GGT C 3095 coding EPI-2203-03 HSGCSFR2 GGG TCG GBG GGT CBG C 3096 HUMITGF EPI-2203-04 TGFP3 GGG TGG GCT T 3097 HUMNK65PRO EPI-2206-01 NFKB/NK & TCell 35 Activating Prot GGG TGG GCT TGG G 3098 HUMPEREEB EPI 2206-02 NFKB/Prostagl. EP3 Rec CCTGGGTGGGBBTGGG 3099 EPI 2206-03 HSNF2B/GCSF NFKB/GranuLocCSF/ 40 Transcr.FactorNF2B CCTGGBTGGGCBTGGG 3100 EPI-2206-04 HUMLAP/NFKB Leuk.Adhes.Prot GCCTGBGTGBBCTTGGG 3101 EP12206-05 NFKB/Endothel N2 S63833 45 CCCAVGVCCVCCCAGGC 3102 EPI 2206-06 NFKBAS13/B Lymph SerThrProt.Kinase AGCCCACCCAGGC 3103 EP12206-07 NFKBAS13/GCSF1 HSGCSFRlRec BCCTGGGTGGGCTB 3104 EP12206-08 NFKBAS13/GCSFl/ 50 NK7TCELLACT.Prot GGTGGGCTTGGG 3105 EPI 2206-09 NFKBAS13/ HSTGFB1 TGFB CCBBGGTGGGCTTGGG 3106 EPI 2206-10 NFKBAS13/ HSTGFB1 TGFB1 55 CTGGGTGGGBBTGGG 3107 EPI 2206-11 NFKBAS13/ HSGCSFR1 GCSFR1 CCBGGGTGGGCTTGG 3108 EPI 2206-12 NFKBAS13/HUMCD30A LymphActAntigCoding GGGTGGGCTTGG 3109 EPI-2206-12B NFKBAS13/HUMCD30A 60 CCTGBGTGBGCBTGGG 3110 EPI 2206-13 NFKBAS13/HUMCAMlV Vasc.Endoth.Cell Adh.Molec B: Universal Base The MTA oligos of Table 3 are suitable for use with two or more of the targets listed in Table 4 65 below.

WO 00/62736 PCT/USOO/08020 299 Table 4:Targets for the MTA Oligos of Table 3 Compound Target EPI 2010 Adenosine Al receptor EPI 2045 Adenosine A3 receptor EPI 2873, EPI 2193 NFKB EPI 1873 Interleukin-1 EPI 1857 Interleukin -5 EPI 2945 Interleukin -4 EP1 2977 Interleukin -8 EPI 2031 5-Lipoxygenase EPI 1898 Leukotriene C-4 Synthase EPI 1856 Eotaxin EPI 1131 ICAM EPI 1085 VCAM EPI 2085 TNFa EPI1908 PAF EPI 1925 IL-4 receptor EPI 2643 P2 aderenergic receptor kinase EPI 2934 Tryptase EPI 2033 Major Basic Protein EPI 2795 Eosinophil Peroxidase NfxB: nuclear factor xB ICAM: intracellular adhesion molecule VCAM: vascular cell adhesion molecule 5 TNF: tumor necrosis factor PAF: platelet activating factor The mRNA sequence of the targeted protein may be derived from the nucleotide sequence of the gene expressing the protein, whether for existing targets or those to be found in the future. Sequences for many target genes of different systems are presently known. See, GenBank data base, 10 NIH, the entire sequences of which are incorporated here by reference. The sequences of those genes, whose sequences are not yet available, may be obtained by isolating the target segments applying technology known in the art. Once the sequence of the gene, its RNA and/or the protein are known, anti-sense oligonucleotides are produced as described above and utilized to validate the target by in vivo administration and testing for a reduction of the production of the targeted protein in accordance 15 with standard techniques, and of specific functions. As already described above, the anti-sense oligonucleotides may be of any suitable length, e.g., from about 7 to about 60 nucleotides in length, depending on the particular target being bound and the mode of delivery thereof. The anti-sense oligonucleotide preferably is directed to an mRNA region containing a junction between intron and exon or to regions vicinal to the junction. Where the anti-sense oligonucleotide is directed to an 20 intron/exon junction, it may either entirely overlie the junction or may be sufficiently close to the junction to inhibit splicing out of the intervening exon during processing of precursor mRNA to mature mRNA, e.g., with the 3' or 5' terminus of the anti-sense oligonucleotide being positioned within about, for example, 10, 5, 3, or 2 nucleotide of the intron/exon junction. Also preferred are anti-sense oligonucleotides which overlap the initiation codon and, more generally, those that target the coding 25 region of the target mRNA. When practicing the present invention, the anti-sense oligonucleotides administered may be related in origin to the species to which it is administered. When treating humans, human anti-sense may be used if desired. Anti-sense oligos to endogenous sequences from other species, however, are also encompassed.

WO 00/62736 PCT/USOO/08020 300 Pharmaceutical compositions comprising an anti-sense oligonucleotide as given above effective to reduce expression of an A, or A 3 adenosine receptor by passing through a cell membrane and binding specifically with mRNA encoding an A, or A 3 adenosine receptor in the cell so as to prevent its translation are another aspect of the present invention. Such compositions are provided in a 5 suitable pharmaceutically acceptable carrier, e.g., sterile pyrogen-free saline solution. The anti-sense oligonucleotides may be formulated with a hydrophobic carrier capable of passing through a cell membrane, e.g., in a liposome, with the liposomes carried in a pharmaceutically acceptable aqueous carrier. The oligonucleotides may also be coupled to a substance which inactivates mRNA, such as a ribozyme. Such oligonucleotides may be administered to a subject to inhibit the activation of a target, 10 such as the adenosine receptors, which subject is in need of such treatment for any of the reasons discussed herein. Furthermore, the pharmaceutical formulation may also contain chimeric molecules comprising anti-sense oligonucleotides attached to molecules which are known to be internalized by cells. These oligonucleotide conjugates utilize cellular uptake pathways to increase cellular concentrations of oligonucleotides. Examples of macromolecules used in this manner include 15 transferrin, asialoglycoprotein (bound to oligonucleotides via polylysine) and streptavidin. In the pharmaceutical formulation, the anti-sense compound may be contained within a lipid particle or vesicle, such as a liposome or microcrystal. The particles may be of any suitable structure, such as unilamellar or plurilamellar, so long as the anti-sense oligonucleotide is contained therein. Positively charged lipids such as N- [1-(2, 3 -dioleoyloxi) propyl] -N, N, N-trimethylammoniumethylsulfate, or 20 "DOTAP," are particularly preferred for such particles and vesicles. The preparation of such lipid particles is well known. See, e.g., U.S. Patent Nos. 4,880,635 to Janoff et al.; 4,906,477 to Kurono et al.; 4,911,928 to Wallach; 4,917,951 to Wallach; 4,920,016 to Allen et al.; 4,921,757 to Wheatley et al.; etc. Subjects may be administered the active composition by any means which transports the anti 25 sense nucleotide composition to the lung. The anti-sense compounds are particularly disclosed herein may be administered to the lungs of a patient by any suitable means, but are preferably administered by generating an aerosol comprised of respirable particles, the respirable particles comprised of the anti sense compound, which particles the subject inhales. The respirable particles may be liquid or solid. The particles may optionally contain other therapeutic ingredients. Particles comprised of anti-sense 30 compound for practicing the present invention should include particles of respirable size: that is, particles of a size sufficiently small to pass through the mouth and larynx upon inhalation and into the bronchi and alveoli of the lungs. In general, particles ranging from about .5 to about 10 microns in size are respirable. Particles of non-respirable size which are included in the aerosol tend to deposit in the throat and be swallowed, and the quantity of non-respirable particles in the aerosol is preferably 35 minimized. For nasal administration, a particle size in the range of 10-500 :m is preferred to ensure retention in the nasal cavity. Thus, particles of about 4, about 10, about 25, about 50 to about 75, about 100, about 250, about 500, and other specific ranges therewithin, are preferred. Others, however, are also contemplated within the confines of this invention. Liquid pharmaceutical compositions of active compound for producing an aerosol can be 40 prepared by combining the anti-sense compound with a suitable vehicle, such as sterile pyrogen free water. Other therapeutic compounds may optionally be included. Solid particulate compositions containing respirable dry particles of micronized anti-sense compound may be prepared by grinding dry anti-sense compound with a mortar and pestle, and then passing the micronized composition through a 400 mesh screen to break up or separate out large agglomerates. A solid particulate 45 composition comprised of the anti-sense compound may optionally contain a dispersant which serves to facilitate the formation of an aerosol. A suitable dispersant is lactose, which may be blended with the anti-sense compound in any suitable ratio (e.g., a 1 to 1 ratio by weight). Again, other therapeutic compounds may also be included. The dosage of the anti-sense compound administered will depend upon the disease being 50 treated, the condition of the subject, the particular formulation, the route of administration, the timing WO 00/62736 PCT/USOO/08020 301 of administration to a subject, etc. In general, intracellular concentrations of the oligonucleotide of from about 0.01, about 0.05, about 0.1, about 0.2, about I to about 5 pM, about 50 [LM, about 100 [M or more, and more particularly about 0.2 to about 0.5 [M, are desired. For administration to a subject such as a human, a dosage of from about 0.01, about 0.1 or about 1 mg/Kg up to about 50, about 100, 5 or about 150 mg/Kg and even higher doses are typically employed depending on the route of administration as is known in the art. Depending on the solubility of the particular formulation of active compound administered, the daily dose may be divided among one or several unit dose administrations. Administration of the anti-sense compounds may be carried out therapeutically (i.e., as a rescue treatment) or prophylactically. Aerosols of liquid particles comprising the anti-sense 10 compound may be produced by any suitable means, such as with a nebulizer. See, e.g., U.S. Patent No. 4,501,729. Nebulizers are commercially available devices which transform solutions or suspensions of the active ingredient into a therapeutic aerosol mist either by means of acceleration of a compressed gas, typically air or oxygen, through a narrow venturi orifice or by means of ultrasonic agitation. Suitable formulations for use in nebulizers consist of the active ingredient in a liquid carrier, 15 the active ingredient comprising up to 40% w/w of the formulation, but preferably less than 20% w/w. The carrier is typically water or a dilute aqueous alcoholic solution, preferably made isotonic with body fluids by the addition of, for example, sodium chloride. Optional additives include preservatives if the formulation is not prepared sterile, for example, methyl hydroxybenzoate, antioxidants, flavoring agents, volatile oils, buffering agents and surfactants. 20 In one preferred embodiment, the pharmaceutical composition comprises nucleic acid(s) which comprise the anti-sense oligo(s) described above and one or more surfactants. Suitable surfactants or surfactant components for enhancing the uptake of the anti-sense oligonucleotides of the invention include synthetic and natural as well as full and truncated forms of surfactant protein A, surfactant protein B, surfactant protein C, surfactant protein D and surfactant Protein E, di-saturated 25 phosphatidylcholine (other than dipalmitoyl), dipalmitoylphosphatidylcholine, phosphatidylcholine, phosphatidylglycerol, phosphatidylinositol, phosphatidylethanolamine, phosphatidylserine; phosphatidic acid, ubiquinones, lysophosphatidylethanolamine, lysophosphatidylcholine, palmitoyl-lysophosphatidylcholine, dehydroepiandrosterone, dolichols, sulfatidic acid, glycerol-3-phosphate, dihydroxyacetone phosphate, glycerol, glycero-3-phosphocholine, 30 dihydroxyacetone, palmitate, cytidine diphosphate (CDP) diacylglycerol, CDP choline, choline, choline phosphate; as well as natural and artificial lamellar bodies which are the natural carrier vehicles for the components of surfactant, omega-3 fatty acids, polyenic acid, polyenoic acid, lecithin, palmitinic acid, non-ionic block copolymers of ethylene or propylene oxides, polyoxypropylene, monomeric and polymeric, polyoxyethylene, monomeric and polymeric, poly (vinyl amine) with 35 dextran and/or alkanoyl side chains, Brij 35, Triton X-100 and synthetic surfactants ALEC, Exosurf, Survan and Atovaquone, among others. These surfactants may be used either as a single, or as part of a multiple component, surfactant in a formulation, or as covalently bound additions to the 5' and/or 3' ends of the anti-sense oligo(s). Aerosols of solid particles comprising the active compound may likewise be produced with any solid particulate medicament aerosol generator. Aerosol generators for 40 administering solid particulate medicaments to a subject produce particles which are respirable, as explained above, and generate a volume of aerosol containing a predetermined metered dose of a medicament at a rate suitable for human administration. One illustrative type of solid particulate aerosol generator is an insufflator. Suitable formulations for administration by insufflation include finely comminuted powders which may be delivered by means of an insufflator or taken into the nasal 45 cavity in the manner of a snuff. In the insufflator, the powder (e.g., a metered dose thereof effective to carry out the treatments described herein) is contained in capsules or cartridges, typically made of gelatin or plastic, which are either pierced or opened in situ and the powder delivered by air drawn through the device upon inhalation or by means of a manually-operated pump. The powder employed in the insufflator consists either solely of the active ingredient or of a powder blend comprising the 50 active ingredient, a suitable powder diluent, such as lactose, and an optional surfactant. The active WO 00/62736 PCT/USOO/08020 302 ingredient typically comprises from 0.1 to 100 w/w of the formulation. A second type of illustrative aerosol generator comprises a metered dose inhaler. Metered dose inhalers are pressurized aerosol dispensers, typically containing a suspension or solution formulation of the active ingredient in a liquefied propellant. During use these devices discharge the formulation through a valve adapted to 5 deliver a metered volume, typically from 10 to 150 :1, to produce a fine particle spray containing the active ingredient. Suitable propellants include certain chlorofluorocarbon compounds, for example, dichlorodifluoromethane, trichlorofluoromethane, dichlorotetrafluoroethane and mixtures thereof. The formulation may additionally contain one or more co-solvents, for example, ethanol, surfactants, such as oleic acid or sorbitan trioleate, antioxidants and suitable flavoring agents. The aerosol, whether 10 formed from solid or liquid particles, may be produced by the aerosol generator for example at a rate of from about 10, about 30, about 70 to about 100, about 150, about 150 liters per minute, more preferably from about 30 to 150 liters per minute, and most preferably about 60 liters per minute. Aerosols containing greater amounts of medicament, however, may be administered more rapidly as is known in the art. 15 The relevant disclosures of all scientific publications and patent references cited in this patent are specifically intended to be incorporated herein by reference, particularly in reference to preparatory methods and technologies which are enabling of the invention. The following examples are provided to illustrate the present invention, and should not be construed as limiting thereon. EXAMPLES 20 In the following examples, :M means micromolar, ml means milliliters, :m means micrometers, mm means millimeters, cm means centimeters, EC means degrees Celsius, :g means micrograms, mg means milligrams, g means grams, kg means kilograms, M means molar, and h or hr. means hours. Example 1: Design and Synthesis of Anti-sense Oligonucleotides 25 The design of anti-sense oligonucleotides against the A, and A 3 adenosine receptors may require the solution of the complex secondary structure of the target A, receptor mRNA and the target A, receptor mRNA. After generating this structure, anti-sense nucleotide are designed which target regions of mRNA which might be construed to confer functional activity or stability to the mRNA and which optimally may overlap the initiation codon. Other target sites are readily usable. As a 30 demonstration of specificity of the anti-sense effect, other oligonucleotides not totally complementary to the target mRNA, but containing identical nucleotide compositions on a w/w basis, are included as controls in anti-sense experiments. The mRNA secondary structure of the adenosine A, receptor was analyzed and used as described above. to design a phosphorothioate anti-sense oligonucleotide. The anti-sense 35 oligonucleotide which was synthesized was designated HAdAAS and had the following sequence: 5' GAT GGA GGG CGG CAT GGC GGG-3' ( SEQ ID NO:1). As a control, a mismatched phosphorothioate anti-sense nucleotide designated HAdA1MM1 was synthesized with the following sequence: 5' -GTA GCA GGC GGG GAT GGG GGC-3' (SEQ ID NO:2). Each oligonucleotide had identical base content and general sequence structure. Homology searches in GENBANK (release 40 85.0) and EMBL (release 40.0) indicated that the anti-sense oligonucleotide was specific for the human and rabbit adenosine A, receptor genes, and that the mismatched control was not a candidate for hybridization with any known gene sequence. The secondary structure of the adenosine A, receptor mRNA was similarly analyzed and used as described above to design two phosphorothioate anti-sense oligonucleotides. The first anti-sense 45 oligonucleotide (HAdA3AS1) synthesized had the following sequence: 5' -GTT GTT GGG CAT CTT GCC-3' (SEQ ID NO:3). As a control, a mismatched phosphorothioate anti-sense oligonucleotide (HAdA3MM 1) was synthesized, having the following sequence: 5' -GTA CTT GCG GAT CTA GGC-3' (SEQ ID NO:4). A second phosphorothioate anti-sense oligonucleotide (HAdA3AS2) was also designed and synthesized, having the following sequence: 5' -GTG GGC CTA WO 00/62736 PCT/USOO/08020 303 GCT CTC GCC-3' (SEQ ID NO:5). Its control oligonucleotide (HAdA3MM2) had the sequence: 5' -GTC GGG GTA CCT GTC GGC-3' (SEQ ID NO:6). Phosphorothioate oligonucleotides were synthesized on an Applied Biosystems Model 396 Oligonucleotide Synthesizer, and purified using NENSORB chromatography (DuPont, MD). 5 Example 2: In Vivo Testing of Adenosine A, Receptor Anti-sense Oligos The anti-sense oligonucleotide against the human A, receptor (SEQ ID NO:1) described above. was tested for efficacy in an in vitro model utilizing lung adenocarcinoma cells HTB-54. HTB 54 lung adenocarcinoma cells were demonstrated to express the A, adenosine receptor using standard 10 northern blotting procedures and receptor probes designed and synthesized in the laboratory. HTB-54 human lung adenocarcinoma cells (106/100 mm tissue culture dish) were exposed to 5.0 :M HAdAJAS or HAdAlMM1 for 24 hours, with a fresh change of media and oligonucleotides after 12 hours of incubation. Following 24 hour exposure to the oligonucleotides, cells were harvested and their RNA extracted by standard procedures. A 21-mer probe corresponding to the region of 15 mRNA targeted by the anti-sense (and therefore having the same sequence as the anti-sense, but not phosphorothioated) was synthesized and used to probe northern blots of RNA prepared from HAdAIAS-treated, HAdAIMM 1-treated and non-treated HTB-54 cells. These blots showed clearly that HAdAIAS but not HAdAlMMl effectively reduced human adenosine receptor mRNA by >50%. This result showed that HAdAIAS is a good candidate for an anti-asthma drug since it depletes intracellular 20 mRNA for the adenosine A, receptor, which is involved in asthma. Example 3: In Vivo Efficacy of Adenosine A, Receptor Anti-sense Oligos A fortuitous homology between the rabbit and human DNA sequences within the adenosine A, gene overlapping the initiation codon permitted the use of the phosphorothioate anti-sense 25 oligonucleotides initially designed for use against the human adenosine A, receptor in a rabbit model. Neonatal New Zealand white Pasteurella-free rabbits were immunized intraperitoneally within 24 hours of birth with 312 antigen units/nl house dustmite (D. farinae) extract (Berkeley Biologicals, Berkeley, CA), mixed with 10% kaolin. Immunizations were repeated weekly for the first month and then biweekly for the next 2 months. At 3-4 months of age, eight sensitized rabbits were anesthetized 30 and relaxed with a mixture of ketamine hydrochloride (44 mg/kg) and acepromazine maleate (0.4 mg/kg) administered intramuscularly. The rabbits were then laid supine in a comfortable position on a small molded, padded animal board and intubated with a 4.0-mm intratracheal tube (Mallinkrodt, Inc., Glens Falls, NY). A polyethylene catheter of external diameter 2.4 mm with an attached latex balloon was passed into the esophagus and maintained at the same distance (approximately 16 cm) from the 35 mouth throughout the experiments. The intratracheal tube was attached to a heated Fleisch pneumotachograph (size 00; DOM Medical, Richmond, VA), and flow was measured using a Validyne differential pressure transducer (Model DP-45161927; Validyne Engineering Corp., Northridge, CA) driven by a Gould carrier amplifier (Model 11-4113; Gould Electronic, Cleveland, OH). The esophageal balloon was attached to one side of the differential pressure transducer, and the outflow of 40 the intratracheal tube was connected to the opposite side of the pressure transducer to allow recording of transpulmonary pressure. Flow was integrated to give a continuous tidal volume, and measurements of total lung resistance (RL) and dynamic compliance (Cdyn) were calculated at isovolumetric and flow zero points, respectively, using an automated respiratory analyzer (Model 6; Buxco, Sharon, CT). Animals were randomized and on Day 1 pretreatment values for PC50 were obtained for aerosolized 45 adenosine. Anti-sense (HAdAlAS) or mismatched control (HAdAlMM) oligonucleotides were dissolved in sterile physiological saline at a concentration of 5000 :g (5 mg) per 1.0 ml. Animals were subsequently administered the aerosolized anti-sense or mismatch oligonucleotide via the intratracheal tube (approximately 5000 :g in a volume of 1.0 ml), twice daily for two days. Aerosols of either saline, adenosine, or anti-sense or mismatch oligonucleotides were generated by an ultrasonic nebulizer 50 (DeVilbiss, Somerset, PA), producing aerosol droplets 80% of which were smaller than 5 :m in WO 00/62736 PCT/USOO/08020 304 diameter. In the first arm of the experiment, four randomly selected allergic rabbits were administered anti-sense oligonucleotide and four the mismatched control oligonucleotide. On the morning of the third day, PC50 values (the concentration of aerosolized adenosine in mg/ml required to reduce the dynamic compliance of the bronchial airway 50% from the baseline value) were obtained and 5 compared to PC50 values obtained for these animals prior to exposure to oligonucleotide. Following a 1 week interval, animals were crossed over, with those previously administered mismatch control oligonucleotide now administered anti-sense oligonucleotide, and those previously treated with anti sense oligonucleotide now administered mismatch control oligonucleotide. Treatment methods and measurements were identical to those employed in the first arm of the experiment. It should be noted 10 that in six of the eight animals treated with anti-sense oligonucleotide, adenosine-mediated bronchoconstriction could not be obtained up to the limit of solubility of adenosine, 20 mg/ml. For the purpose of calculation, PC50 values for these animals were set at 20 mg/ml. The values given therefore represent a minimum figure for anti-sense effectiveness. Actual effectiveness was higher. The results of this experiment are illustrated in Table 5 below. 15 Table 5: Effect of Adenosine A, Receptor Anti-sense Oligo upon PC50 Values in Asthmatic Rabbits Mismatch Control A, Receptor Anti-sense Oligo Pre Oligonucleotide Post Oligonucleotide IPre Oligonucleotide Post Oligonucleotide 3.56 1.02 5.16 1.03 2.36 0.68 >19.5 ±0.34** The results are presented as the mean (n=8) + SEM. The significance was determined by repeated-measures analysis of variance (ANOVA), and Tukey's protected test. 20 **Significantly different from all other groups, p<0.01. In both arms of the experiment, animals receiving the anti-sense oligonucleotide showed an order of magnitude increase in the dose of aerosolized adenosine required to reduce dynamic compliance of the lung by 50%. No effect of the mismatched control oligonucleotide upon PC50 values was observed. No toxicity was observed in any animal receiving either anti-sense or control 25 inhaled oligonucleotide. These results show clearly that the lung has exceptional potential as a target for anti-sense oligonucleotide-based therapeutic intervention in lung disease. They further show, in a model system which closely resembles human asthma, that downregulation of the adenosine A, receptor largely eliminates adenosine-mediated bronchoconstriction in asthmatic airways. Bronchial hyperresponsiveness in the allergic rabbit model of human asthma is an excellent endpoint for anti 30 sense intervention since the tissues involved in this response lie near to the point of contact with aerosolized oligonucleotides, and the model closely simulates an important human disease. Example 4: Specificity of A,-adenosine Receptor Anti-sense Oligonucleotide At the conclusion of the cross-over experiment of Example 3 above, airway smooth muscle from all rabbits was quantitatively analyzed for adenosine A, receptor number. As a control for the 35 specificity of the anti-sense oligonucleotide, adenosine A 2 receptors, which should not have been affected, were also quantified. Airway smooth muscle tissue was dissected from each rabbit and a membrane fraction prepared according to the method of Kleinstein et al. (Kleinstein, J. and Glossmann, H., Naunyn-Schmiedeberg's Arch. Pharmacol. 305: 191-200 (1978)), the relevant portion of which is hereby incorporated in its entirety by reference, with slight modifications. Crude plasma 40 membrane preparations were stored at 70EC until the time of assay. Protein content was determined by the method of Bradford (M. Bradford, Anal. Biochem. 72, 240-254 (1976), the relevant portion of which is hereby incorporated in its entirety by reference). Frozen plasma membranes were thawed at room temperature and were incubated with 0.2 U/ml adenosine deaminase for 30 minutes at 37EC to remove endogenous adenosine. The binding of [ 3 H] DPCPX (A, receptor-specific) or [ 3 H] CGS-21680 45 (A, receptor-specific) was measured as previously described by Ali et al. (Ali, S. et al., J. Pharmacol. Exp. Ther. 268, Am. J. Physiol 266, L271-277 (1994), the relevant portion of which is hereby incorporated in its entirety by reference). The animals treated with adenosine A, anti-sense oligonucleotide in the cross-over experiment had a nearly 75% decrease in A, receptor number compared to controls, as assayed by specific binding of the A,-specific antagonist DPCPX. There was WO 00/62736 PCT/USOO/08020 305 no change in adenosine A 2 receptor number, as assayed by specific binding of the A 2 receptor-specific agonist 2- [p- (2-carboxyethyl)-phenethylamino] -5' - (N-ethylcarboxamido) adenosine (CGS-21680). This is illustrated in Table 6 below. Table 6: Specificity of Action of Adenosine A, 5 Receptor Oligonucleotide Anti-sense Mismatch Control A, Anti-sense Oligonucleotide Oligonucleotide A,-Specific Binding 1105 48** 293 18

A

2 -Specific Binding 302 22 442 171 The results are presented as the mean (n = 8) ± SEM. The significance was determined by repeated-measures analysis of variance (ANOVA), and Tukey's protected test. 10 *Significantly different from mismatch control, p<0.01. The above results illustrate the effectiveness of anti-sense oligonucleotides in treating airway disease. Since the anti-sense oligos described above. eliminate the receptor systems responsible for adenosine-mediated bronchoconstriction, it may be less imperative to eliminate adenosine from them. 15 However, it would be preferable to eliminate adenosine from even these oligonucleotides to reduce the dose needed to attain a similar effect. Described above are other anti-sense oligonucleotides targeting mRNA of proteins involved in inflammation. Adenosine has been eliminated from their nucleotide content to prevent its liberation during degradation. Example 5: Anti-sense Oligos directed to other Target Nucleic Acids 20 This work was conducted to demonstrate that the present invention is broadly applicable to anti-sense oligonucleotides ("oligos") specific to nucleic acid targets broadly. The following experimental studies were conducted to show that the method of the invention is broadly suitable for use with anti-sense oligos designed as taught by this application and targeted to any and all adenosine receptor mRNAs. For this purpose, various anti-sense oligos were porepared to adenosine receptor 25 mRNAs exemplified by the adenosine A 1 , A 2 b and A, receptor mRNAs. Anti-sense Oligo I was disclosed above (SEQ. ID NO:1).Five additional anti-sense phosphorothioate oligos were designed asnd synthesized as indicated above. I- Oligo II (SEQ. ID NO: 7) also targeted to the adenosine A I receptor, but to a different region than Oligo I. 2- Oligo V (SEQ. ID NO: 10) targeted to the adenosine A2b receptor. 30 3- Oligos III (SEQ. ID NO: 8) and IV (SEQ. ID NO: 9) targeted to different regions of the adenosine A 3 receptor. 4- Oligo I-PD (SEQ. ID NO: 1681)(a phosphodiester oligo of the same sequence as Oligo I). These anti-sense oligos were designed for therapy on a selected species as described above and are generally specific for that species, unless the segment of the target mRNA of other species 35 happens to contain a similar sequences. All anti-sense oligos were prepared as described below, and tested in vivo in a rabbit model for bronchoconstriction, inflammation and allergy, which have breathing difficulties and impeded lung airways, as is the case in ailments such as asthma, as described in the above-identified application. Example 6: Design & Sequences of other Anti-sense Oligos 40 Six oligos and their effects in a rabbit model were studied and the results of these studies are reported and discussed below. Five of these oligos were selected for this study to complement the data on Oligo I (SEQ ID NO: 1) provided in Examples I to 4 above. This oligo is anti-sense to one region of the adenosine A, receptor mRNA. The oligos tested are identified as anti-sense Oligos I (SEQ ID NO: 1) and II (SEQ. ID No: 7) targeted to a different region of the adenosine A, receptor mRNA, 45 Oligo V (SEQ. ID No:8) targeted to the adenosine A 2 b receptor mRNA, and anti-sense Oligos III and IV (SEQ. ID NOS: 9 and 10) targeted to two different regions of the adenosine A, receptor mRNA. The sixth oligo (Oligo I-PD) is a phosphodiester version of Oligo I (SEQ. ID NO:1). The design and synthesis of these anti-sense oligos was performed in accordance with Example 1 above. (I) Anti-sense Oligo I 50 The anti-sense oligonucleotide I referred to in Examples 1 to 4 above is targeted to the human WO 00/62736 PCT/USOO/08020 306 A, adenosine receptor mRNA (EPI 2010). Anti-sense oligo I is 21 nucleotide long, overlaps the initiation codon, and has the following sequence:5'-GAT GGA GGG CGG CAT GGC GGG-3'(SEQ.ID NO:1). The oligo I was previously shown to abrogate the adenosine-induced bronchoconstriction in allergic rabbits, and to reduce allergen-induced airway obstruction and bronchial hyperresponsiveness 5 (BHR), as discussed above and shown by Nyce, J. W. & Metzger, W. J., Nature, 385:721 (1977), the relevant portions of which reference are incorporated in their entireties herein by reference. (II) Anti-sense Oligo II A phosphorothioate anti-sense oligo (SEQ. ID NO:7) was designed in accordance with the invention to target the rabbit adenosine A, receptor mRNA region +936 to +956 relative to the 10 initiation codon (start site). The anti-sense oligo II is 21 nucleotide long, and has the following sequence: 5'-CTC GTC GCC GTC GCC GGC GGG-3' (SEQ. ID NO:7). (III) Anti-sense Oligo III A phosphorothioate anti-sense oligo other than that provided in Example 1 above (SEQ. ID NO:8) was designed in accordance with the invention to target the anti-sense A, receptor mRNA 15 region +3 to + 22 relative to the initiation codon start site. The anti-sense oligo III is 20 nucleotide long, and has the following sequence: 5'-GGG TGG TGC TAT TGT CGG GC-3' (SEQ. ID NO:8). (IV) Anti-sense Oligo IV Yet another phosphorothioate anti-sense oligo (SEQ. ID NO:9) was designed in accordance with the invention to target the adenosine A 3 receptor mRNA region + 386 to + 401 relative to the 20 initiation codon (start site). The anti-sense oligo IV is 15 nucleotide long, and has the following sequence: 5'-GGC CCA GGG CCA GCC-3' (SEQ. ID NO:9) (V) Anti-sense Oligo V A phosphorothioate anti-sense oligo (SEQ. ID NO:10) was designed in accordance with the invention to target the adenosine A 2 b receptor mRNA region -21 to -1 relative to the initiation codon 25 (start site). The anti-sense oligonucleotide V is 21 nucleotide long, and has the following sequence: 5' GGC CGG GCC AGC CGG GCC CGG-3' (SEQ. ID NO:10). (VI) A, Mismatch Oligos Two different mismatched oligonucleotides having the following sequences were used as controls for anti-sense oligo I(SEQ. ID NO: 1) described in Example 5 above: A, MM2:5'-GTA GGT 30 GGC GGG CAA GGC GGG-3' (SEQ. ID NO:2421), and A, MM3:5'-GAT GGA GGC GGG CAT GGC GGG-3' (SEQ. ID NO:2422). Anti-sense oligo I and the two mismatch anti-sense oligos had identical base content and general sequence structure. Homology searches in GENBANK (release 85.0) and EMBL (release 40.0) indicated that the anti-sense oligo I was specific, not only for the human, but also for the rabbit, adenosine A, receptor genes, and that the mismatched controls were not 35 candidates for hybridization with any known human or animal gene sequence. (VII) Anti-sense Oligo A,-PD (Oligo VI) A phosphodiester anti-sense oligo (Oligo VI; SEQ. ID NO:2420) having the same nucleotide sequence as Oligo I was designed as disclosed in the above-identified application. Anti-sense oligo I PD is 21 nucleotide long, overlaps the initiation codon, and has the following sequence: 5'- GAT GGA 40 GGG CGG CAT GGC GGG-3' (SEQ. ID NO:2420). III) Controls Each rabbit was administered 5.0 ml aerosolized sterile saline following the same schedule as for the anti-sense oligos in (II), (III), and (IV) above. Example 7: Synthesis of Anti-sense Oligos 45 Phosphorothioate anti-sense oligos having the sequences described in (a) above, were synthesized on an Applied Biosystems Model 396 Oligonucleotide Synthesizer, and purified using NENSORB chromatography (DuPont, DE). TETD (tetraethylthiuram disulfide) was used as the sulfurizing agent during the synthesis. Anti-sense oligonucleotide II (SEQ. ID NO:7), anti-sense oligonucleotide III (SEQ. ID NO: 8) and anti-sense oligonucleotide IV (SEQ. ID NO: 9) were each 50 synthesized and purified in this manner.

WO 00/62736 PCT/US00/08020 307 Example 8: Preparation of Allergic Rabbits Neonatal New Zealand white Pasturella-free rabbits were immunized intraperitoneally within 24 hours of birth with 0.5 ml of 312 antigen units/mi house dust mite (D. farinae) extract (Berkeley Biologicals, Berkeley, CA) mixed with 10% kaolin as previously described (Metzger, W. J., in Late 5 Phase Allergic Reactions, Dorsch, W., Ed., CRC Handbook, pp. 347-362, CRC Press, Boca Raton (1990); Ali, S., Metzger, W. J. and Mustafa, S. J., Am. J. Resp. Crit. Care Med. 149: 908 (1994)), the relevant portions of which are incorporated in their entireties here by reference. Immunizations were repeated weekly for the first month and then biweekly until the age of 4 months. These rabbits preferentially produce allergen-specific IgE antibody, typically respond to aeroallergen challenge with 10 both an early and late-phase asthmatic response, and show bronchial hyper responsiveness (BHR). Monthly intraperitoneal administration of allergen (312 units dust mite allergen, as above) continues to stimulate and maintain allergen-specific IgE antibody and BHR. At 4 months of age, sensitized rabbits were prepared for aerosol administration as described by Ali et al. (Ali, S., Metzger, W. J. and Mustafa, S. J., Am. J. Resp. Crit. Care Med. 149 (1994)), the relevant section being incorporated in its entirety 15 here by reference. DOSE-RESPONSE STUDIES Example 9: Experimental Setup Aerosols of either adenosine (0-20 mg/ml), or anti-sense or one of two mismatch oligonucleotides (5 mg/ml) were separately prepared with an ultrasonic nebulizer (Model 646, 20 DeVilbiss, Somerset, PA), which produced aerosol droplets, 80% of which were smaller than 5:m in diameter. Equal volumes of the aerosols were administered directly to the lungs via an intratracheal tube. The animals were randomized, and administered aerosolized adenosine. Day 1 pre-treatment values for sensitivity to adenosine were calculated as the dose of adenosine causing a 50% loss of compliance (PC 5 Adenosine). The animals were then administered either the aerosolized anti-sense or 25 one of the mismatch anti-sense oligos via the intratracheal tube (5 mg/1.0 ml), for 2 minutes, twice daily for 2 days (total dose, 20 mg). Post-treatment PC 5 0 values were recorded (post-treatment challenge) on the morning of the third day. The results of these studies are provided in Example 21 below. Example 10: Crossover Experiments 30 For some experiments utilizing anti-sense oligo I (SEQ ID NO: 1) and a corresponding mismatch control oligonucleotide AIMM2, following a 2 week interval, the animals were crossed over, with those previously administered the mismatch control AMM2, now receiving the anti-sense oligo I, and those previously treated with the anti-sense oligo I, now receiving the mismatch control AMM2 oligo. The number of animals per group was as follows. For mismatch AMM2 (Control 1), 35 n=7, since one animal was lost in the second control arm of the experiment due to technical difficulties, for mismatch AMM3 n=4 (Control 2) and for AIAS anti-sense oligo I, n=8. The AMM3 oligo-treated animals were analyzed separately and were not part of the cross-over experiment. The treatment methods and measurements employed following the cross-over were identical to those employed in the first arm of the experiment. In 6 of the 8 animals treated with the anti-sense oligo I (SEQ. ID NO: 1), 40 no PC 50 value could be obtained for adenosine doses of up to 20 mg/ml, which is the limit of solubility of adenosine. Accordingly, the PC,, values for these animals were assumed to be 20 mg/ml for calculation purposes. The values given, therefore, represent a minimum figure for the effectiveness of the anti-sense oligonucleotides of the invention. Other groups of allergic rabbits (n=4 for each group) were administered 0.5 or 0.05 mg doses of the anti-sense oligo I (SEQ ID NO: 1), or the AMM2 oligo 45 in the manner and according to the schedule described above (the total doses being 2.0 or 0.2 mg). The results of these studies are provided in Example 22 below. Example 11: Anti-sense Oligo Formulation Each one of anti-sense oligos were separately solubilized in an aqueous solution and WO 00/62736 PCT/USOO/08020 308 administered as described for anti-sense oligo I (SEQ. ID No:1) in (e) above, in four 5 mg aliquots (20 mg total dose) by means of a nebulizer via endotracheal tube, as described above. The results obtained for anti-sense oligo I and its mismatch controls confirmed that the mismatch controls are equivalent to saline, as described in Example 19 below and in Table 1 of Nyce & Metzger, Nature 385: 721-725 5 (1997). Because of this finding, saline was used as a control for pulmonary function studies employing anti-sense oligos II, III and IV (SEQ. IS NOS; 7, 8 and 9). Example 12: Specificity of Oligo I for Adenosine A, Receptor (Receptor Binding Studies) Tissue from airway smooth muscle was dissected to primary, secondary and tertiary bronchi from rabbits which had been administered 20 mg oligo I (SEQ ID NO: 1) in 4 divided doses over a 10 period of 48 hours as described above. A membrane fraction was prepared according to the method of Ali et al. (Ali, S., et al., Am. J. Resp. Crit. Care Med. 149: 908 (1994), the relevant section relating to the preparation of the membrane fraction is incorporated in its entirety hereby by reference). The protein content was determined by the method of Bradford and plasma membranes were incubated with 0.2 U/ml adenosine deaminase for 30 minutes at 37EC to remove endogenous adenosine. See, 15 Bradford, M. M. Anal. Biochem. 72, 240-254 (1976), the relevant portion of which is hereby incorporated in its entirety by reference. The binding of [ 3 H]DPCPX, [ 3 H]NPC17731, or [ 3

H]CGS

21680 was measured as described by Jarvis et al. See, Jarvis, M.F., et al., Pharmacol. Exptl. Ther. 251, 888-893 (1989), the relevant portion of which is fully incorporated herein by reference. The results of this study are shown in Table 8 and discussed in Example 20 below. 20 Example 13: Pulmonary Function Measurements (Compliance cDYN and Resistance) At 4 months of age, the immunized animals were anesthetized and relaxed with 1.5 ml of a mixture of ketamine HCl (35 mg/kg) and acepromazine maleate (1.5 mg/kg) administered intramuscularly. After induction of anesthesia, allergic rabbits were comfortably positioned supine on a 25 soft molded animal board. Salve was applied to the eyes to prevent drying, and they were closed. The animals were then intubated with a 4.0 mm intermediate high-low cuffed Murphy 1 endotracheal tube (Mallinckrodt, Glen Falls, NY), as previously described by Zavala and Rhodes. See, Zavala and Rhodes, Proc. Soc. Exp. Biol. Med. 144: 509-512 (1973), the relevant portion of which is incorporated herein by reference in its entirety. A polyethylene catheter of OD 2.4 mm (Becton Dickinson, Clay 30 Adams, Parsippany NJ) with an attached thin-walled latex balloon was passed into the esophagus and maintained at the same distance (approximately 16 cm) from the mouth throughout the experiment. The endotracheal tube was attached to a heated Fleisch pneumotach (size 00; DEM Medical, Richmond, VA), and the flow (v) measured using a Validyne differential pressure transducer (Model DP-45-16-1927, Validyne Engineering, Northridge, CA), driven by a Gould carrier amplifier (Model 35 11-4113, Gould Electronics, Cleveland, OH). An esophageal balloon was attached to one side of the Validyne differential pressure transducer, and the other side was attached to the outflow of the endotracheal tube to obtain transpulmonary pressure (P,). The flow was integrated to yield a continuous tidal volume, and the measurements of total lung resistance (R,) and dynamic compliance (Cdy,) were made at isovolumetric and zero flow points. The flow, volume and pressure were recorded 40 on an eight channel Gould 2000 W high-frequency recorder and Cdy, was calculated using the total volume and the difference in Pt, at zero flow, and . R, was calculated as the ratio of Ptp and V at midtidal lung volumes. These calculations were made automatically with the Buxco automated pulmonary mechanics respiratory analyzer (Model 6, Buxco Electronics, Sharon, CT), as previously described by Giles et al. See, Giles et al., Arch. Int. Pharmacodyn. Ther. 194: 213-232 (1971), the 45 relevant portion of which describing these calculations is incorporated in toto hereby by reference. The results obtained upon administration of oligo II on allergic rabbits are shown and discussed in Example 26 below. Example 14: Measurement of Bronchial Hyperresponsiveness (BHR) Each allergic rabbit was administered histamine by aerosol to determine their baseline WO 00/62736 PCT/USOO/08020 309 hyperresponsiveness. Aerosols of either saline or histamine were generated using a DeVilbiss nebulizer (DeVilbiss, Somerset, PA) for 30 seconds and then for 2 minutes at each dose employed. The ultrasonic nebulizer produced aerosol droplets of which 80% were <5 micron in diameter. The histamine aerosol was administered in increasing concentrations (0.156 to 80 mg/ml) and 5 measurements of pulmonary function were made after each dose. The B4R was then determined by calculating the concentration of histamine (mg/ml) required to reduce the Cdyn 50% from baseline (PC,, Histamine) Example 15: Cardiovascular Effect of Anti-sense Oligo I The measurement of cardiac output and other cardiovascular parameters using CardiomaxJ 10 utilizes the principal of thermal dilution in which the change in temperature of the blood exiting the heart after a venous injection of a known volume of cool saline is monitored. A single rapid injection of cool saline was made into the right atrium via cannulation of the right jugular vein, and the corresponding changes in temperature of the mixed injectate and blood in the aortic arch were recorded via cannulation of the carotid artery by a temperature-sensing miniprobe. Twelve hours after the 15 allergic rabbits had been treated with aerosols of oligo I (EPI 2010; SEQ. ID NO: 1) as described in (d) above, the animals were anesthetized with 0.3 ml/kg of 80% Ketamine and 20% Xylazine. This time point coincides with previous data showing efficacy for SEQ. ID NO: 1, as is clearly shown by Nyce & Metzger, (1997), supra, the pertinent disclosure being incorporated in its entirety here by reference. A thermocouple was then inserted into the left carotid artery of each rabbit, and was then advanced 6.5 20 cm and secured with a silk ligature. The right jugular vein was then cannulated and a length of polyethylene tubing was inserted and secured. A thermodilution curve was then established on a CardiomaxJ II (Columbus Instruments, Ohio) by injecting sterile saline at 20EC to determine the correctness of positioning of the thermocouple probe. After establishing the correctness of the position of the thermocouple, the femoral artery and vein were isolated. The femoral vein was used as a portal 25 for drug injections, and the femoral artery for blood pressure and heart rate measurements. Once constant baseline cardiovascular parameters were established, CardiomaxJ measurements of blood pressure, heart rate, cardiac output, total peripheral resistance, and cardiac contractility were made. Example 16: Duration of Action of Oligo I (SEQ. ID NO: 1) Eight allergic rabbits received initially increasing log doses of adenosine by means of a 30 nebulizer via an intra-tracheal tube as described in (f) above, beginning with 0.156 mg/ml until compliance was reduced by 50% (PCSO Adenosine) to establish a baseline. Six of the rabbits then received four 5 mg aerosolized doses of (SEQ. ID NO: 1) as described above. Two rabbits received equivalent amounts of saline vehicle as controls. Beginning 18 hours after the last treatment, the PC 5 0 Adenosine values were tested again. After this point, the measurements were continued for all animals each day, 35 for up to 10 days. The results of this study are discussed in Example 25 below. Example 17: Reduction of Adenosine A2b Receptor Number by Anti-sense Oligo V Sprague Dawley rats were administered 2.0 mg respirable anti-sense oligo V (SEQ ID NO:10) three times over two days using an inhalation chamber as described above. Twelve hours after 40 the last administration, lung parenchymal tissue was dissected and assayed for adenosine Asb receptor binding using [311]-NECA as described by Nyce & Metzger (1997), supra. Controls were conducted by administration of equal volumes of saline. The results are significant at p<0.05 using Student's paired t test, and are discussed in Example 28 below. Example 18: Comparison of Oligo I & Corresponding 45 Phosphodiester Oligo VI (SEQ. ID NO:1681) Oligo I (SEQ ID NO:1) countered the effects of adenosine and eliminated sensitivity to it for adenosine amounte up to 20 mg adenosine/5.0 ml (the limit of solubility of adenosine). Oligo VI (SEQ ID NO:1681), the phosphodiester version of the oligonucleotide sequence, was completely ineffective when tested in the same manner. Both compounds have identical sequence, differing only in the WO 00/62736 PCT/USOO/08020 310 presence of phosphorothioate residues in Oligo I (SEQ ID NO:1), and were delivered as an aerosol as described above and in Nyce & Metzger (1997), supra. Significantly different at p<0.001, Student's paired t test. The results are discussed in Example 29 below. RESULTS OBTAINED FOR ANTI-SENSE OLIGO I (SEQ. ID NO: 1) 5 Example 19: Results of Prior Work The nucleotide sequence and other data for anti-sense oligo I (SEQ. ID NO: 1), which is specific for the adenosine A, receptor, were provided above. The experimental data showing the effectiveness of oligo I in down regulating the receptor number and activity were also provided above. Further information on the characteristics and activities of anti-sense oligo I is provided in Nyce, J. W. 10 and Metzger, W. J., Nature 385:721 (1997), the relevant parts of which relating to the following results are incorporated in their entireties herein by reference. The Nyce & Metzger (1997) publication provided data showing that the anti-sense oligo I (SEQ. ID NO: 1): (1) The anti-sense oligo I reduces the number of adenosine A, receptors in the bronchial smooth muscle of allergic rabbits in a dose-dependent manner as may be seen in Table 5 15 below. (2) Anti-sense Oligo I attenuates adenosine-induced bronchoconstriction and allergen induced bronchoconstriction. (3) The Oligo I attenuates bronchial hyperresponsiveness as measured by PC,, histamine, a standard measurement to assess bronchial hyperresponsiveness. This result clearly 20 demonstrates anti-inflammatory activity of the anti-sense oligo I as is shown in Table 5 above. (4) As expected, because it was designed to target it, the anti-sense oligo I is totally specific for the adenosine A, receptor, and has no effect at all at any dose on either the very closely related adenosine A 2 receptor or the related bradykinin B 2 receptor. This is seen in Table 5 25 below. (5) In contradistinction to the above effects of the Oligo I, the mismatch control molecules MM2 and MM3 (SEQ. ID NO:1682 and SEQ. ID NO:1683) which have identical base composition and molecular weight but differed from the anti-sense oligo I (SEQ ID NO: 1) by 6 and 2 mismatches, respectively. These mismatches, which are the minimum possible 30 while still retaining identical base composition, produced absolutely no effect upon any of the targeted receptors (A,, A 2 or B 2 ). These results, along with a complete lack of prior art on the use of anti-sense oligonucleotides, such as oligo I, targeted to the adenosine A, receptor, are unexpected results. The showings presented in this patent clearly enable and demonstrate the effectiveness, for their intended use, of the claimed 35 agents and method for treating a disease or condition associated with lung airway, such as bronchoconstriction, inflammation, allergy(ies), and the like. Example 20: Oligo I Significantly Reduces Response to Adenosine Challenge The receptor binding experiment is described in Example 12 above, and the results shown in 40 Table 5 below which shows the binding characteristics of the adenosine A,-selective ligand

[

3 H]DPCPX and the bradykinin B 2 -selective ligand [ 3 H]NPC 17731 in membranes isolated from airway smooth muscle of A, adenosine receptor and B 2 bradykinin receptor anti-sense- and mismatch treated allergic rabbits. Table 5: Binding Characteristics of Three Anti-Sense Oligos Treatment' A, receptor B 2 receptor Kd Bmax Kd Bmax Adenosine A, Receptor 20 mg 0.36±0.029 nM 19±1.52 fnoles* 0.39±0.031 nM 14.8+0.99fmoles WO 00/62736 PCT/US00/08020 311 2 mg 0.38±0.030 nM 32±2.56 frnoles* 0.41±0.028 nM 15.5±1.08 0.2 mg 0.37±0.030 nM 49±3.43 fmoles 0.34±0.024 nM #9*1.06 AMM1 (Control) fmoles 20 mg 0.34±0.027 nM 52.0±3.64 fmoles 0.35±0.024 nM 14.0±1.0 fmoles 2 mg 0.37±0.033 nM 51.8±3.88 fmoles 0.38±0.028 nM 14.6±1.02

B

2 A (Bradykinin Receptor) fmoies 20 mg 0.36±0.028 nM 45.0±3.15 fmoles 0.38±0.027 nM 8.7±0.62 2 mg 0.39±0.035 nM 44.3±2.90 fmoles 0.34±0.024 nM P9W6 0.2 mg 0.40±0.028 nM 47.0±3.76 fmoles 0.35±0.028 nM in.11*05 files

B

2 MM tpfi~Lrui) 0.39±0.031 nM 42.0±2.94 fmoles 0.41±0.029 nM 14.0±0.98 foles 2 mng 0.41±0.035 nM 40.0±3.20 fmoles 0.37±0.030 nM 14.8±0.99 files 0.2 mg 0.37±0.029 nM 43.0±3.14 fmoles 0.36±0.025 nM 15.1±1.35 fmoles Saline Control 0.37±0.041 46.0±5.21 0.39±0.047 nM 14.2±1.35 fmoles 1 Refers to total oligo administered in four equivalently divided doses over a 48 hour period. Treatments and analyses were performed as described in methods. Significance was determined by repeated-measures analysis of variance (ANOVA), and Tukeys protected t test. n = 4-6 for all groups. * Significantly different from mismatch control- and saline-treated groups, p<0.001; 5 **Significantly different from mismatch control- and saline-treated groups, p3<0.05. Example 21: Dose-response Effect of Oligo I Anti-sense oligo I (SEQ ID NO: 1) was found to reduce the effect of adenosine administration to the animal in a dose-dependent manner over the dose range tested as shown in Table 6 below. Table 6: Dose-Response Effect to Anti-sense Oligo I 10 Total Dose PC 50 Adenosine (miz) (mg Adenosine) Anti-sense Oligo I 0.2 8.32±7.2 2.0 14.0±7.2 15 20 19.5±0.34 A.0M2 oligo (control) 0.2 2.51±0.46 2.0 3.13± 0.71 20 3.25± 0.34 20 The above results were studied with the Student's paired t test and found to be statistically different. p=0.05 The oligo I (SEQ. ID NO:1), an anti-adenosine A, receptor oligo, acts specifically on the adenosine A, receptor, but not on the adenosine A 2 receptors. These results stem from the treatment of rabbits with anti-sense oligo I (SEQ. ID NO.1) or mismatch control oligo (SEQ. ID NO:1682; 25 AMM2) as described in Example 9 above and in Nyce & Metzger (1997), supra (four doses of 5 mng spaced 8 to 12 hours apart via nebulizer via endotracheal tube), bronchial smooth muscle tissue excised and the number of adenosine A, and adenosine A, receptors determined as reported in Nyce & Metzger (1997), supra. Example 22: Specificity of Oligo I (SEQ. ID NO: 1) 30 for Target Gene Product Oligo I (SEQ. ID No: 1) is specific for the adenosine A, receptor whereas its mismatch controls had no activity. Figure 1 depicts the results obtained from the cross-over experiment described in Example 10 above and in Nyce & Metzger (1997), supra. The two mismatch controls (SEQ. ID NO: 1682 and SEQ. ID NO: 1683) evidenced no effect on the PC,, Adenoine value. On the contrary, the 35 administration of anti-sense oligo I (SEQ. ID NO:1I) showed a seven-fold increase in the PC,, Adenosine WO 00/62736 PCT/USOO/08020 312 value. The results clearly indicate that the anti-sense oligo I (SEQ. ID NO: 1) reduces the response (attenuates the sensitivity) to exogenously administered adenosine when compared with a saline control. The results provided in Table 6 above clearly establish that the effect of the anti-sense oligo I is dose dependent (see, column 3 of Table 5). The Oligo I was also shown to be totally specific for the 5 adenosine A, receptor, (see, top 3 rows of Table), inducing no activity at either the closely related adenosine A 2 receptor or the bradykinin B 2 receptor (see, lines 8-10 of Table 6 above). In addition, the results shown in Table 6 establish that the anti-sense oligo I (SEQ. ID NO:1) decreases sensitivity to adenosine in a dose dependent manner, and that it does this in an anti-sense oligo-dependent manner since neither of two mismatch control oligonucleotides (AMM2; SEQ. ID NO:1682 and AMM3; 10 SEQ. ID NO:1683) show any effect on PC 50 Adenosine values or on attenuating the number of adenosine A, receptors. Example 23: Effect on Aeroallergen-induced Bronchoconstriction & Inflammation The Oligo I (SEQ. ID NO:1) was shown to significantly reduce the histamine-induced effect 15 in the rabbit model when compared to the mismatch oligos. The effect of the anti-sense Oligo I (SEQ. ID No:l) and the mismatch oligos (AIMM2, SEQ. ID NO:1682 and AIMM3, SEQ. ID NO:1682) on allergen-induced airway obstruction and bronchial hyperresponsiveness was assessed in allergic rabbits. The effect of the anti-sense oligo I (SEQ. ID NO:1) on allergen-induced airway obstruction was assessed. As calculated from the area under the plotted curve, the anti-sense oligo I significantly 20 inhibited allergen-induced airway obstruction when compared with the mismatched control (55%, p<0.05; repeated measures ANOVA, and Tukey's t test). A complete lack of effect was induced by the mismatch oligo AMM2 (Control) on allergen induced airway obstruction. The effect of the anti-sense oligo I (SEQ. ID NO:1) on allergen-induced BHR was determined as above. As calculated from the

PC

50 Histamine value , the anti-sense oligo I (SEQ. ID NO:1) significantly inhibited allergen-induced BHR 25 in allergic rabbits when compared to the mismatched control (61%, p<0.05; repeated measures ANOVA, Tukey's t test). A complete lack of effect of the AMM mismatch control on allergen induced BHR was observed. The results indicated that anti-sense oligo I (SEQ. ID NO: 1) is effective to protect against aeroallergen-induced bronchoconstriction (house dust mite). In addition, the anti sense oligo I (SEQ. ID NO:1) was also found to be a potent inhibitor of dust mite-induced bronchial 30 hyper responsiveness, as shown by its effects upon histamine sensitivity which indicates anti inflammatory activity for anti-sense oligo I (SEQ. ID NO:1). Example 24: Anti-sense Oligo I is Free of Deleterious Side Effects The Oligo I (SEQ. ID NO:1) was shown to be free of side effects that might be toxic to the 35 recipient. No changes in arterial blood pressure, cardiac output, stroke volume, heart rate, total peripheral resistance or heart contractility (dPdT) were observed following administration of 2.0 or 20 mg oligo I (SEQ. ID NO:1). The addition, the results of the measurement of cardiac output (CO), stroke volume (SV), mean arterial pressure (MAP), heart rate (HR), total peripheral resistance (TPR), and contractility (dPdT) with a CardiomaxJ apparatus (Columbus Instruments, Ohio) were assessed. 40 These results evidenced that oligo I (SEQ. ID NO:1) has no detrimental effect upon critical cardiovascular parameters. More particularly, this oligo does not cause hypotension. This finding is of particular importance because other phosphorothioate anti-sense oligonucleotides have been shown in the past to induce hypotension in some model systems. Furthermore, the adenosine A, receptor plays an important role in sinoatrial conduction within the heart. Attenuation of the adenosine A, receptor by 45 anti-sense oligo I (SEQ. ID NO:1) might be expected to result, therefore, in deleterious extrapulmonary activity in response to the downregulation of the receptor. This is not the case. The anti-sense oligo I (SEQ. ID NO:1) does not produce any deleterious intrapulmonary effects and renders the administration of the low doses of the present anti-sense oligo free of unexpected, undesirable side effects. This demonstrates that when oligo I (SEQ. ID NO:1) is administered directly 50 to the lung, it does not reach the heart in significant quantities to cause deleterious effects. This is in WO 00/62736 PCT/USOO/08020 313 contrast to traditional adenosine receptor antagonists like theophylline which do escape the lung and can cause deleterious, even life-threatening effects outside the lung. Example 25: Long Lasting Effect of Oligo I The Oligo I (SEQ. ID NO:1) evidenced a long lasting effect as evidenced by the PC,, and 5 Resistance values obtained upon its administration prior to adenosine challenge. The duration of the effect was measured for with respect to the PC,, of adenosine anti-sense oligo I when administered in four equal doses of 5 mg each by means of a nebulizer via an endotracheal tube, as described above. The effect of the agent is significant over days 1 to 8 after administration. When the effect of the anti sense oligo I (SEQ. ID NO:1) had disappeared, the animals were administered saline aerosols 10 (controls), and the PC 5 0 Adenosine values for all animals were measured again. Saline-treated animals showed base line PC,, adenosine values (n=6). The duration of the effect (with respect to Resistance) was measured for six allergic rabbits which were administered 20 mg of anti-sense oligo I (SEQ. ID NO: 1) as described above, upon airway resistance measured as also described above. The mean calculated duration of effect was 8.3 days for both PC,, adenosine (p<0.05) and resistance (p<0.05). 15 These results show that anti-sense oligo I (SEQ. ID NO:1) has an extremely long duration of action, which is completely unexpected. Example 26: Anti-sense Oligo II Anti-sense oligo II, targeted to a different region of the adenosine A, receptor mRNA, was found to be highly active against the adenosine A,-mediated effects. The experiment measured the 20 effect of the administration of anti-sense oligo II (SEQ. ID NO:7) upon compliance and resistance values when 20 mg anti-sense oligo II or saline (control) were administered to two groups of allergic rabbits as described above. Compliance and resistance values were measured following an administration of adenosine or saline as described above in Example 13. The effect of the anti-sense oligo of the invention was different from the control in a statistically significant manner, p<0.05 using 25 paired t-test, compliance; p<0.01 for resistance. The results showed that anti-sense oligo II (SEQ. ID NO:7), which targets the adenosine A, receptor, effectively maintains compliance and reduces resistance upon adenosine challenge. Example 27: Antisense Oligos III and IV Oligos III (SEQ. ID NO:8) and IV (SEQ. ID NO:9) were shown to be in fact specifically 30 targeted to the adenosine A, receptor by their effect on reducing inflammation and the number of inflammatory cells present upon separate administration of 20 mg of the anti-sense oligos III (SEQ. ID NO:8) and IV (SEQ. ID NO:9) to allergic rabbits as described above. The number of inflammatory cells was determined in their bronchial lavage fluid 3 hours later by counting at least 100 viable cells per lavage. The effect of anti-sense oligos III (SEQ. ID NO:8) and IV (SEQ. ID NO:9) upon 35 granulocytes, and upon total cells in bronchial lavage were assessed following exposure to dust mite allergen. The results showed that the anti-sense oligo IV (SEQ. ID NO:9) and anti-sense oligo III (SEQ. ID NO:8) are very potent anti-inflammatory agents in the asthmatic lung following exposure to dust mite allergen. As is known in the art, granulocytes, especially eosinophils, are the primary inflammatory cells of asthma, and the administration of anti-sense oligos III (SEQ. ID NO:8) and IV 40 (SEQ. ID NO:9) reduced their numbers by 40% and 66%, respectively. Furthermore, anti-sense oligos IV (SEQ. ID NO:9) and III (SEQ. ID NO:8) also reduced the total number of cells in the bronchial lavage fluid by 40% and 80%, respectively. This is also an important indicator of anti-inflammatory activity by the present anti-adenosine A 3 agents of the invention. Inflammation is known to underlie bronchial hyperresponsiveness and allergen-induced bronchoconstriction in asthma. Both anti-sense 45 oligonucleotides III.(SEQ. ID NO:8) and IV (SEQ. ID NO:9), which are targeted to the adenosine A, receptor, are representative of an important new class of anti-inflammatory agents which may be designed to specifically target the lung receptors of each species. Example 28: Anti-sense Oligo V WO 00/62736 PCT/USOO/08020 314 The anti-sense oligo V (SEQ. ID NO:10) , targeted to the adenosine A 2 b adenosine receptor mRNA was shown to be highly effective at countering adenosine A 2 b-mediated effects and at reducing the number of adenosine A 2 b receptors present to less than half. Example 29: Unexpected Superiority of Substituted 5 over Phosphodiester-residue Oligo I-DS (SEQ. ID NO:1681) Oligos I (SEQ. ID NO:1) and I-DS (SEQ. ID NO:1681) were separately administered to allergic rabbits as described above, and the rabbits were then challenged with adenosine. The phosphodiester oligo I-DS (SEQ. ID NO:1681) was statistically significantly less effective in 10 countering the effect of adenosine whereas oligo I (SEQ. ID NO:1) showed high effectiveness, evidencing a PC 5 Adenosine of 20 mg. Example 30: Anti-sense Oligo VI For the present work, I designed an additional anti-sense phosphorothioate oligo targeted to the adenosine A, receptor (Oligo VI). This anti-sense oligo was designed for therapy on a selected 15 species as described in the above patent application and is generally specific for that species, unless the segment of the adenosine receptor mRNA of other species elected happens to have a similar sequence. The anti-sense oligos were prepared as described below, and tested in vivo in a rabbit model for bronchoconstriction, inflammation and lung allergy, which have breathing difficulties and impeded lung airways, as is the case in ailments such as asthma, as described in the above-identified application. 20 One additional oligo and its effect in a rabbit model was studied and the results of the study are reported and discussed below. The present oligo (anti-sense oligo VI) was selected for this study to complement the data on SEQ ID NO: 1 (Oligo I), which is anti-sense to the adenosine A, receptor mRNA provided in the above-identified patent application. This additional oligo is identified as anti sense Oligo VI, and is targeted to a different region of the adenosine A, receptor mRNA than Oligo I. 25 The design and synthesis of this anti-sense oligo was performed in accordance with the teaching, particularly Example 1, of the above-identified patent application. The anti-sense Oligo VI is a phosphorothioate designed to target the coding region of the rabbit adenosine A, receptor mRNA region +964 to +984 relative to the initiation codon (start site). The Oligo VI was prepared as described in the above-indicated application, and is 20 nucleotides long. The OligoVI is directed to the adenosine 30 A, receptor gene, and has the following sequence: 5'-CGC CGG CGG GTG CGG GCC GG-3' (SEQ. ID NO:_). The phosphorothioate anti-sense Oligo VI having the sequence described in (5) above, was synthesized on an Applied Biosystems Model 396 Oligonucleotide Synthesizer, and purified using NENSORB chromatography (DuPont, DE). TETD (tetraethylthiuram disulfide) was used as the sulfurizing agent during the synthesis. 35 Example 31: Preparation of Allergic Rabbits Neonatal New Zealand white Pasturella-free rabbits were immunized intraperitoneally within 24 hours of birth with 0.5 ml of 312 antigen units/ml house dust mite (D. farinae) extract (Berkeley Biologicals, Berkeley, CA) mixed with 10% kaolin as previously described (Metzger, W. J., in Late Phase Allergic Reactions, Dorsch, W., Ed., CRC Handbook, pp 347-362, CRC Press, Boca Raton, 40 1990; Ali, S. Et al., Am. J. Resp. Crit. Care Med. 149: 908 (1994)). The immunizations were repeated weekly for the first month and then bi-weekly until the animals were 4 months old. These rabbits preferentially produce allergen-specific IgE antibody, typically respond to aeroallergen challenge with both an early and late-phase asthmatic response, and show bronchial hyper responsiveness (BHR). Monthly intraperitoneal administration of allergen (312 units dust mite allergen, as above) continues to 45 stimulate and maintain allergen-specific IgE antibody and BHR. At 4 months of age, sensitized rabbits were prepared for aerosol administration as described by Ali et al. (1994), supra. Example 32: Adenosine Aerosol Preparation An adenosine aerosol (20 mg/ml) was prepared with an ultrasonic nebulizer (Model 646, DeVilbiss, Somerset, PA), which produced aerosol droplets, 80% of which were smaller than 5:m in WO 00/62736 PCT/USOO/08020 315 diameter. Equal volumes of the aerosols were administered directly to the lungs via an intratracheal tube to all three rabbits. The animals were then administered the aerosolized adenosine and Day 1 pre treatment values for sensitivity to adenosine were calculated as the dose of adenosine causing a 50% loss of compliance (PCo Adenosine). The animals were then administered the aerosolized anti-sense 5 via the intratracheal tube (5 mg/1.0 ml), for 2 minutes, twice daily for 2 days (total dose, 20 mg). Post treatment PC 5 s values were recorded (post-treatment challenge) on the morning of the third day. The results of these studies are provided in (9) below. Example 33: Anti-sense Oligo Formulation Each one of anti-sense oligos were separately solubilized in an aqueous solution and 10 administered as described for anti-sense oligo I in (e) above, in four 5 mg aliquots (20 mg total dose) by means of a nebulizer via endotracheal tube, as described above. Example 34: Oligo VI Reduces Response to Adenosine Challenge as well or Better than Oligo I Oligo VI was tested in three allergic rabbits of the characteristics and readied as described in 15 (7) above and in the above-indicated patent application. Oligo VI targets a section of the coding region of the A, receptor which is different from Oligo I. Both these target sequences were selected randomly from many possible coding region target sequences. The three rabbits were treated identically as previously indicated for Oligo I. Briefly, 5 mg of Oligo VI were nebulized to the rabbits twice per day at 8 hour intervals, for two days. Thereafter, PC,, adenosine studies were performed on the morning of 20 the third day and compared to pre-treatment PC 5 values. This protocol is described in more detail in Nyce and Metzger (Nyce & Metzger, Nature 385: 721-725 (1997)). The results obtained for the three rabbits are shown in Table 7 below. Table 7: PC 50 Adenosine before & after Aerosolized Adenosine Treatment 25 Treatment Time PCs, Adenosine (mg) Pre-treatment 3.0 ±2.1 Post-treatment >20.0* * maximum achievable dose due to adenosine insolubility in saline 30 All three animals treated with Oligo VI completely eliminated sensitivity to adenosine up to the measurable level of the agent shown in Table 7 above. That is, the administration of the Oligo VI abrogated the adenosine-induced bronchoconstriction in the three allergic rabbits. The actual efficacy of Oligo VI is, therefore, greater than could be measured in the experimental system used. By comparing with the previously submitted results for the Oligo I, it may be seen that the Oligo VI was 35 found to be as effective, or more, than Oligo I. Example 34: Conclusions The work described and results discussed in the examples clearly indicates that all anti-sense oligonucleotides designed in accordance with the teachings of the above-identified application were found to be highly effective at countering or reducing effects mediated by the receptors they are 40 targeted to. That is, each and all of the two anti-sense oligos targeting an adenosine A, receptor mRNA, 1 anti-sense oligo targeting an adenosine A 2 b receptor mRNA, and the 2 anti-sense oligos targeting an A, receptor mRNA were shown capable of countering the effect of exogenously administered adenosine which is mediated by the specific receptor they are targeted to. The activity of the anti-sense oligos of this invention, moreover, is specific to the target and substitutively fails to inhibit another 45 target. In addition, the results presented also show that the administration of the present agents results in extremely low or non-existent deleterious side effects or toxicity. This represents 100% success in providing agents that are highly effective and specific in the treatment of bronchoconstriction and/or inflammation. This invention is broadly applicable in the same manner to all gene(s) and corresponding mRNAs encoding proteins involved in or associated with airway diseases. A WO 00/62736 PCT/USOO/08020 316 comparison of the phosphodiester and a version of the same oligonucleotide wherein the phosphodiester bonds are substituted with phosphorothioate bonds evidenced an unexpected superiority for the phosphothiorate oligonucleotide over the phosphodiester anti-sense oligo. Example 35: In Vivo Response to Adenosine Challenge 5 with & without Oligo I Pretreatment Two hyper responsive monkeys (ascaris sensitive) were challenged with inhaled adenosine, with and without pre-treatment with anti-sense oligo I (SEQ.ID NO: 1). The PC 40 adenosine was calculated from the data collected as being equivalent to that amount of adenosine in mg that causes a 40% decrease in dynamic compliance in hyper-responsive airways. The Oligo I (SEQ. ID NO:1; EPI 10 2010) was subsequently administered at 10 mg/day for 2 days by inhalation. On the third day, the PC adenosine was again measured. The PCo adenosine value prior to treatment with Oligo I was compared side-by-side with to the PC 40 adenosine taken after administration of Oligo I (Figure not shown). The results of the experiment conducted with two animals showed that any sensitivity to adenosine was completely eliminated by the administration of the oligo of this invention in one animal, 15 and substantially reduced in the second. Example 36: Extension of the experimental Results The method of the present invention is also practiced with anti-sense oligonucleotides targeted to many genes, mRNAs and their corresponding proteins as described above, in essentially the same manner as given above, for the treatment of various conditions in the lungs. Examples of these are 20 Human A2a adenosine receptor, Human A2b adenosine receptor, Human IgE receptor P, Human Fc epsilon receptor CD23 antigen (IgE receptor), Human IgE receptor, a subunit, Human IgE receptor, Fc epsilon R, Human histidine decarboxylase, Human beta tryptase, Human tryptase-I, Human prostaglandin D synthase, Human cyclooxygenase-2, Human eosinophil cationic protein, Human eosinophil derived neurotoxin, Human eosinophil peroxidase, Human intercellular adhesion molecule 25 1 (CAM-1), Human vascular cell adhesion molecule 1 (VCAM-1), Human endothelial leukocyte adhesion molecule (ELAM-1), Human P Selectin, Human endothelial monocyte activating factor, Human IL3, Human IL4, Human IL5, Human IL6, Human monocyte-derived neutrophil chemotactic factor, Human neutrophil elastase (medullasin), Human neutrophil oxidase factor, Human cathepsin G, Human defensin 1, Human defensin 3, Human macrophage inflammatory protein-I-alpha, Human 30 muscarinic acetylcholine receptor HMI, Human muscarinic acetylcholine receptor HM3, Human fibronectin, Human interleukin 8, Human GM-CSF, Human tumor necrosis factor a, Human leukotriene C4 synthase, Human major basic protein, and many more. The foregoing examples are illustrative of the present invention, and are not to be construed as limiting thereof. The invention is defined by the following claims, with equivalents of the claims to be 35 included therein.

Claims (91)

1. A pharmaceutical composition, comprising an oligonucleotide(s) (oligo(s)) which is (are) effective for alleviating bronchoconstriction and/or lung inflammation, allergy(ies), or surfactant depletion or hyposecretion, when administered to a mammal, the oligo containing about 0 to about 15% adenosine (A) and being anti-sense to a target selected from the group consisting of the initiation codon, the coding region, the 5'-end and the 3'-end genomic flanking regions, the 5' and 3' intron-exon junctions, and regions within 2 to 10 nucleotides of the junctions of a gene encoding a target polypeptide associated with lung airway dysfunction or anti sense to the polypeptide mRNA; combinations of the oligos; and mixtures of the oligos; and a pharmaceutically or veterinarily acceptable carrier or diluent.

2. The composition of claim 1, wherein the oligo is A-free.

3. The composition of claim 1, wherein the target is selected from the group consisting of the initiation codon, the coding region, the 5'-end and the 3'-end genomic flanking regions, the 5' and 3' intron-exon junctions, and regions within 2 to 10 nucleotides of the junctions of an oncogene(s) and a gene(s) encoding a target polypeptide(s) associated with lung airway dysfunction or anti-sense to the oncogene mRNA and the polypeptide mRNA; combinations of the oligos; and mixtures of the oligos; the polypeptides being selected from the group consisting of peptide factors and transmitters, antibodies, cytokines and chemokines, enzymes, binding proteins, adhesion molecules, their receptors, and malignancy associated proteins.

4. The composition of claim 3, wherein the target is selected from the group consisting of the initiation codon, the coding region, the 5'-end and the 3'-end genomic flanking regions, the 5' and 3' intron-exon junctions, and regions within 2 to 10 nucleotides of the junctions of an oncogene(s) and a gene(s) encoding a target polypeptide(s) associated with lung airway dysfunction or anti-sense to the oncogene mRNA and the polypeptide mRNA; combinations of the oligos; and mixtures of the oligos; wherein the polypeptides are selected from the group consisting of transcription factors, stimulating and activating peptide factors, cytokines, cytokine receptors, chemokines, chemokine receptors, adenosine receptors, bradykinin receptors, endogenously produced specific and non-specific enzymes, immunoglobulins and antibodies, antibody receptors, central nervous system (CNS) and peripheral nervous and non-nervous system receptors, CNS and peripheral nervous and non-nervous system peptide transmitters, adhesion molecules, defensins, growth factors, vasoactive peptides and receptors, binding proteins, and malignancy associated proteins.

5. The agent of claim 4, wherein the encoded polypeptide(s) is(are) selected from the group consisting of adenosine receptors A1, A2a, A2b and A3, bradykinin receptors BI and B2, Nf6B Transcription Factor, Interleukin-8 Receptor (IL-8 R), Interleukin 5 Receptor (IL-5 R), Interleukin 4 Receptor (IL-4 R), Interleukin 3 Receptor (IL-3 R), Interleukin- 1 (IL-1 ), Interleukin 1 Receptor (IL- 1 R), Eotaxin, Tryptase, Major Basic Protein, P2-adrenergic Receptor Kinase, Endothelin Receptor A, Endothelin Receptor B, Preproendothelin, Bradykinin B2 Receptor, IgE High Affinity Receptor, Interleukin 1 (IL-1), Interleukin 1 Receptor (IL-1 R), Interleukin 9 (IL-9), Interleukin-9 Receptor (IL-9 R), Interleukin 11 (IL-11), Interleukin- 11 Receptor (IL-11 R), Inducible Nitric Oxide Synthase, Cyclo-oxygenase- 1 (COX- 1), Cyclo-oxygenase-2 (COX-2), Intracellular Adhesion Molecule 1 (ICAM- 1) Vascular Cellular Adhesion Molecule (VCAM), Rantes, Endothelial Leukocyte Adhesion Molecule (ELAM-1), Monocyte Activating Factor, Neutrophil Chemotactic Factor, Neutrophil Elastase, Defensin 1, 2 and 3, Muscarinic Acetylcholine Receptors, Platelet Activating Factor, Tumor Necrosis Factor a, 5-lipoxygenase, Phosphodiesterase IV, Substance P, Substance P Receptor, Histamine Receptor, Chymase, CCR-1 CC Chemokine Receptor, CCR-2 CC Chemokine Receptor, CCR-3 CC Chemokine Receptor, CCR-4 CC Chemokine Receptor, CCR-5 CC Chemokine Receptor, Prostanoid Receptors, GATA-3 Transcription Factor, Neutrophil Adherence Receptor, MAP Kinase, Interleukin-9 (IL-9), NFAT Transcription Factors, STAT 4, MIP-la, MCP-2, MCP-3, MCP-4, Cyclophillins, Phospholipase A2, Basic Fibroblast Growth Factor, Metalloproteinase, CSBP/p38 MAP WO 00/62736 PCT/USOO/08020 318 Kinase, Tryptose Receptor, PDG2, Interleukin-3 (IL-3), Interleukin-1p (IL-1 ), Cyclosporin A Binding Protein, FK5-Binding Protein, a4pl Selectin, Fibronectin, a4p7 Selectin, Mad CAM-1, LFA I (CDlla/CD18), PECAM-1, LFA-1 Selectin, C3bi, PSGL-1, E-Selectin, P-Selectin, CD-34, L Selectin, p150,95, Mac-I (CD1 lb/CD18), Fucosyl transferase, VLA-4, CD-18/CD Ila, CDI lb/CD18, ICAM2 and ICAM3, C5a, CCR3 (Eotaxin Receptor), CCRI, CCR2, CCR4, CCR5, LTB-4, AP-1 Transcription Factor, Protein kinase C, Cysteinyl Leukotriene Receptor, Tachychinnen Receptors (tach R), 16B Kinase I & 2, STAT 6, c-mas and NF-Interleukin-6 (NF-IL-6).

6. The composition of claim 1, wherein one or more As is(are) substituted by a universal base selected from the group consisting of heteroaromatic bases which bind to a thymidine base but have antagonist activity and less than about 0.3 of the adenosine base agonist or antagonist activity at the adenosine Ai, A 2 a, A 2 and A, receptors.

7. The composition of claim 6, wherein the heteroaromatic bases are selected from the group consisting of pyrimidines and purines, which may be substituted by 0, halo, NH 2 , SH, SO, SO2, SO3, COOH and branched and fused primary and secondary amino, alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, alkoxy, alkenoxy, acyl, cycloacyl, arylacyl, alkynoxy, cycloalkoxy, aroyl, arylthio, arylsulfoxyl, halocycloalkyl, alkylcycloalkyl, alkenylcycloalkyl, alkynylcycloalkyl, haloaryl, alkylaryl, alkenylaryl, alkynylaryl, arylalkyl, arylalkenyl, arylalkynyl, arylcycloalkyl, which may be further substituted by 0, halo, NH 2 , primary, secondary and tertiary amine, SH, SO, SO 2 , SO3, cycloalkyl, heterocycloalkyl and heteroaryl.

8. The composition of claim 7, wherein the pyrimidines and purines are substituted at a position selected from the group consisting of positions 1, 2, 3, 4, 7, and 8, and the pyrimidines and purines are selected from the group consisting of theophylline, caffeine, dyphylline, etophylline, acephylline piperazine, bamifylline, enprofylline and xantine having the chemical formula 0 N C ., wherein R' and R 2 are independently H, alkyl, alkenyl or alkynyl and R 3 is H, aryl, dicycloalkyl, dicycloalkenyl, dicycloalkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, 0-cycloalkyl, 0 cycloalkenyl, O-cycloalkynyl, NH 2 -alkylamino-ketoxyalkyloxy-aryl and mono and dialkylaminoalkyl N-alkylamino-S0 2 aryl.

9. The composition of claim 8, wherein the universal base is selected from the group consisting of 3-nitropyrrole-2'-deoxynucleoside, 5-nitro-indole, 2-deoxyribosyl-(5-nitroindole), 2 deoxyribofuranosyl-(5-nitroindole), 2'-deoxyinosine, 2'-deoxynebularine, 6H, 8H-3,4-dihydropyrimido [4,5-c] oxazine-7-one or 2-amino-6-methoxyaminopurine.

10. The composition of claim 1, where one or more methylated cytocine(s) ('C) is(are) substituted for a C in one or more CpG dinocleotide(s), if present in the oligo(s).

11. The composition of claim 1, wherein one or more mononucleotide(s) of the oligo(s) is(are) linked or modified by one or more methylphosphonate, 5'-N-carbamate, phosphotriester, phosphorothioate, phosphorodithioate, boranophosphate, formacetal, thioformacetal, thioether, carbonate, carbamate, sulfate, sulfonate, sulfamate, sulfonamide, sulfone, sulfite, sulfoxide, sulfide, hydroxylamine, methylene(methyimino) (MMI), methoxymethyl (MOM), methoxyethyl (MOE), methyleneoxy (methylimino) (MOMI), 2'-O-methyl, phosphoramidate, C-5 substituted residues, or combinations thereof.

12. The composition of claim 11, wherein the mononucleotide residues are linked by phosphorothioate residues.

13. The composition of claim 1, wherein the anti-sense oligo comprises about 7 to about 60 mononucleotides.

14. The composition of claim 1, wherein the anti-sense oligo comprises fragments 1, 3, WO 00/62736 PCT/USOO/08020 319 5, 7 and 8 to 2313 (SEQ. ID NOS: 1 through 2419).

15. The composition of claim 1, wherein the anti-sense oligo is operatively linked to, or complexed with, an agent selected from the group consisting of cell internalized or up-taken agents and cell targeting agents.

16. The composition of claim 15, wherein the cell internalized or up-taken agent is selected from the group consisting of transferrin, asialoglycoprotein and streptavidin.

17. The composition of claim 1, wherein the oligo is operatively linked to a vector that is a prokaryotic or eukaryotic vector.

18. The composition of claim 1, wherein the oligo(s) is(are) hybridized to a ribonucleic acid.

19. A cell, carrying the oligo of claim 1.

20. The composition of claim 1, wherein the carrier or diluent is selected from the group consisting of gaseous, liquid, and solid carriers or diluents.

21. The composition of claim 20, further comprising an agent selected from the group consisting of other therapeutic agents, surfactants, flavoring and coloring agents, fillers, volatile oils, buffering agents, dispersants, RNA inactivating agents, anti-oxidants, flavoring agents, propellants and preservatives.

22. The composition of claim 21, comprising one or more oligo(s), a surfactant, and a carrier or diluent for the oligo and the surfactant.

23. The composition of claim 21, wherein the the agent is an RNA inactivating agent which comprises an enzyme, optionally an ribozyme.

24. The composition of claim 1, wherein the anti-sense oligo is present in an amount of about 0.01 to about 99.99 w/w of the composition.

25. The composition of claim 1, which is a systemic or topical formulation.

26. The formulation of claim 25, selected from the group consisting of oral, intrabuccal, intrapulmonary, rectal, intrauterine, intratunor, intracranial, nasal, intramuscular, subcutaneous, intravascular, intrathecal, inhalable, transdermal, intradermal, intracavitary, implantable, iontophoretic, ocular, vaginal, intraarticular, otical, intravenous, intramuscular, intraglandular, intraorgan, intralymphatic, implantable, slow release and enteric coating formulations.

27. The formulation of claim 26, which is an oral formulation, wherein the carrier is selected from the group consisting of solid and liquid carriers.

28. The oral formulation of claim 27, which is selected from the group consisting of a powder, dragees, tablets, capsules, sprays, aerosols, solutions, suspensions and emulsions, optionally oil-in-water and water-in-oil emulsions.

29. The formulation of claim 25, which is a topical formulation, wherein the carrier is selected from the group consisting of creams, gels, ointments, sprays, aerosols, patches, solutions, suspensions and emulsions.

30. The formulation of claim 26, which is an injectable formulation, wherein the carrier is selected from the group consisting of aqueous and alcoholic solutions and suspensions, oily solutions and suspensions and oil-in-water and water-in-oil emulsions.

31. The formulation of claim 26, which is a rectal formulation, optionally a suppository.

32. The formulation of claim 26, which is a transdermal formulation, wherein the carrier is selected from the group consisting of aqueous and alcoholic solutions, oily solutions and suspensions and oil-in-water and water-in-oil emulsions.

33. The transdermal formulation of claim 32, which is an iontophoretic transdermal formulation, wherein the carrier is selected from the group consisting of aqueous and alcoholic solutions, oily solutions and suspensions and oil-in-water and water-in-oil emulsions, and wherein the formulation further comprises a transdermal transport promoting agent.

34. The formulation of claim 26, which is provided in an implant, a capsule or a cartridge. WO 00/62736 PCT/USOO/08020 320

35. The composition of claim 20, wherein the carrier is selected from the group consisting of aqueous and alcoholic solutions and suspensions, oily solutions and suspensions and oil in-water and water-in-oil emulsions.

36. The formulation of claim 20, wherein the carrier comprises a hydrophobic carrier.

37. The formulation of claim 36, wherein the carrier comprises lipid vesicles, optionally liposomes, or particles, optionally microcrystals.

38. The formulation of claim 37, wherein the carrier comprises liposomes, and the liposomes comprise the anti-sense oligo.

39. The formulation of claim 26, which is a respirable or inhalable formulation, optionally an aerosol.

40. The composition of claim 1, in single or multiple unit form.

41. The composition of claim 1, in bulk.

42. A kit, comprising a delivery device; in a separate container(s), the oligo(s) of claim 1; and instructions for adding a carrier and for use of the kit.

43. The kit of claim 42, wherein the formulation is a respirable formulation and the delivery device comprises a nebulizer which delivers single metered doses of the formulation.

44. The kit of claim 43, wherein the nebulizer comprises an insufflator and the composition is provided in a piercable or openable capsule or cartridge.

45. The kit of claim 44, wherein the delivery device comprises a pressurized inhaler and the composition comprises a suspension, solution or dry formulation of the oligo.

46. The kit of claim 45, further comprising, in a separate container, an agent selected from the group consisting of other therapeutic agents, surfactants, anti-oxidants, flavoring agents, fillers, volatile oils, dispersants, antioxidants, propellants, preservatives, buffering agents, RNA inactivating agents, cell-internalized or up-taken agents and coloring agents.

47. The kit of claim 46, comprising, in separate containers, one or more oligos, one or more surfactants, and a carrier or diluent, and optionally other therapeutic agents.

48. The kit of claim 42, wherein the device is a transdermal delivery device, and the kit further comprises a transdermal delivery agent, a transdermal carrier or diluent, and instructions for preparing a transdermal delivery formulation.

49. The kit of claim 42, wherein the device is an iontophoretic delivery device, and the kit further comprises iontophoretic agents and instructions for preparing an iontophoretic formulation.

50. An in vivo method of delivering an anti-sense oligonucleotide(s) (oligo(s)) to one or more target polynucleotide(s), comprising administering into the respiratory system of a subject one or more oligo(s) that are anti-sense to the polynucleotide(s), in an amount effective to reach and hybridize to the target polynucleotide(s), and reduce the production or availability, or to increase the degradation, of the target mRNA, or to reduce the amount of the target polypeptide present in the lungs.

51. An in vivo method of delivering an anti-sense oligonucleotide (oligo) to a target polynucleotide associated with bronchoconstriction and/or lung inflammation, allergy(ies) and/or surfactant hypoproduction, comprising administering to a subject the composition of claim 1, that comprises an amount of the oligo(s) effective to reach and hybridize to the target polynucleotide(s), and reduce or inhibit the polynucleotide(s)' transcription and/or expression and, thereby, alleviating bronchoconstriction and/or lung inflammation, allergy(ies) and/or surfactant hypoproduction.

52. The method of claim 51, wherein the administered composition comprises an amount of the oligo(s) and is administered under conditions effective for alleviating bronchoconstriction and/or lung inflammation, allergy(ies) and/or surfactant depletion or hyposecretion, when administered to a mammal.

53. The method of claim 51, wherein the composition is administered into the subject's respiratory system. WO 00/62736 PCT/USOO/08020 321

54. The method of claim 53, wherein the composition is administered directly into the subject's lung (s).

55. The method of claim 51, wherein the administered composition comprises an amount of the oligo(s) and is administered under conditions effective to reduce the production or availability, or to increase the degradation, of the target mRNA or to reduce the amount of the target polypeptide present in the lungs.

56. The method of claim 51, wherein the agent is administered as a respirable aerosol.

57. The method of claim 51, wherein the pulmonary obstruction, and/or bronchoconstriction and\or lung inflammation, allergy(ies) and/or surfactant hypoproduction are associated with a disease or condition selected from the group consisting of pulmonary vasoconstriction, inflammation, allergies, asthma, impeded respiration, respiratory distress syndrome (RDS), pain, cystic fibrosis (CF), allergic rhynitis (AR), pulmonary hypertension, emphysema, chronic obstructive pulmonary disease (COPD), pulmonary transplantation rejection, pulmonary infections, bronchitis, and cancer.

58. The method of claim 57, wherein the disease or condition is associated with an allergy(ies), and the oligo is anti-sense to a target selected from the group consisting of the initiation codon,the coding region, the 5'-end and the 3'-end genomic flanking regions, the 5' and 3' intron-exon junctions, and regions within 2 to 10 nucleotides of the junctions of a gene(s) encoding an immunoglobulin(s) and antibody(ies) and immunoglobulin and antibody receptors or are anti-sense to the immunoglobulin(s) and antibody(ies) and immunoglobulin and antibody receptors mRNA; combinations of the oligo(s); and mixtures of the oligos.

59. The method of claim 57, wherein the disease or condition is associated with a malignancy or cancer, and the.oligo is anti-sense to a target selected from the group consisting of the initiation codon,the coding region, the 5'-end and the 3'-end genomic flanking regions, the 5' and 3' intron-exon junctions, and regions within 2 to 10 nucleotides of the junctions of an oncogene(s) and\or encodes a malignancy associated protein, or is(are) anti-sense to the oncogene or malignancy associated protein mRNA; combinations of the oligo(s); and mixtures of the oligos and the oligo(s) is(are) administered in an amount effective to reduce either the level of the protein mRNA or of the malignancy associated protein, or to reduce the growth of or provide beneficial characteristics to malignant cells.

60. The method of claim 51, wherein the composition is administered transdermally or systemically.

61. The method of claim 60, wherein the composition is administered orally, intracavitarily, intranasally, intraanally, intravaginally, intrauterally, intraarticularly, transdermally, intrabucally, intravenously, subcutaneously, intramuscularly, intravascularly, intratumorously, intraglandularly, intraocularly, intracranial, into an organ, intravascularly, intrathecally, intralymphatically, intraotically, by implantation, by inhalation, intradermally, intrapulmonarily, intraotically, by slow release, by sustained release and by a pump.

62. The method of claim 51, wherein the subject is a non-human mammal.

63. The method of claim 51, wherein the mammal is a human.

64. The method of claim 51, wherein the oligo is administered in amount of about 0.005 to about 150 mg/kg body weight.

65. The method of claim 51, wherein the oligo is obtained by (a) selecting fragments of a target nucleic acid having at least 4 contiguous nucleic acids selected from the group consisting of G and C; (b) obtaining a first oligonucleotide 4 to 60 nucleotides long which comprises the selected fragment and has a C and G nucleic acid content of up to and including about 15%; and (c) obtaining a second oligonucleotide 4 to 60 nucleotides long comprising a sequence which is anti-sense to the selected fragment, the second oligonucleotide having an A base content of up to and including about 15%. WO 00/62736 PCT/USOO/08020 322 65. The method of claim 64, wherein the oligo is A-free.

66. The method of claim 51, wherein the target is selected from the group consisting of the initiation codon, the coding region, the 5'-end and the 3'-end genomic flanking regions, the 5' and 3' intron-exon junctions, and regions within 2 to 10 nucleotides of the junctions of an oncogene or a gene encoding a target polypeptide associated with lung airway dysfunction or anti-sense to the polypeptide or oncogene mRNA; combinations of the oligo(s); and mixtures of the oligos; wherein the polypeptide isselected from the group consisting of transcription factors, stimulating and activating factors, interleukins, interleukin receptors, chemokines, chemokine receptors, endogenously produced specific and non-specific enzymes, immunoglobulins, antibody receptors, central nervous system (CNS) and peripheral nervous and non-nervous system receptors, CNS and peripheral nervous and non-nervous system peptide transmitters, adhesion molecules, defensines, growth factors, vasoactive peptides, peptide receptors and binding proteins, and malignancy associated proteins.

67. The method of claim 51, wherein one or more As in the oligo(s) is(are) substituted by a universal base selected from the group consisting of heteroaromatic bases which bind to a thymidine base but have less than about 0.3 of the adenosine base agonist or antagonist activity at an adenosine A,, Aa, A 2 b and A, receptors.

68. The method of claim 67, wherein the heteroaromatic bases are selected from the group consisting of pyrimidines and purines, which may be substituted by 0, halo, NH 2 , SH, SO, SO 2 , SO 3 , COOH and branched and fused primary and secondary amino, alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, alkoxy, alkenoxy, acyl, cycloacyl, arylacyl, alkynoxy, cycloalkoxy, aroyl, arylthio, arylsulfoxyl, halocycloalkyl, alkylcycloalkyl, alkenylcycloalkyl, alkynylcycloalkyl, haloaryl, alkylaryl, alkenylaryl, alkynylaryl, arylalkyl, arylalkenyl, arylalkynyl, arylcycloalkyl, which may be further substituted by 0, halo, NH 2 , primary, secondary and tertiary amine, SH, SO, SO 2 , SO3, cycloalkyl, heterocycloalkyl and heteroaryl.

69. The method of claim 67, wherein the pyrimidines and purines are substituted at positions 1, 2, 3, 4, 7 and 8 and the pyrimidines and purines are selected from the group consisting of theophylline, caffeine, dyphylline, etophylline, acephylline piperazine, bamifylline, enprofylline and xantine having the chemical formula a H 11 1 N CI I ii R wherein R' and R 2 are independently H, alkyl, alkenyl or alkynyl and R 3 is H, aryl, dicycloalkyl, dicycloalkenyl, dicycloalkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, 0-cycloalkyl, O-cycloalkenyl, 0-cycloalkynyl, NH 2 -alkylamino-ketoxyalkyloxy-aryl and mono and dialkylaminoalkyl-N alkylamino-S0 2 aryl.

70. The method of claim 69, wherein the universal base is selected from the group consisting of 3-nitropyrrole-2'-deoxynucleoside, 5-nitro-indole, 2-deoxyribosyl-(5-nitroindole), 2 deoxyribofuranosyl-(5-nitroindole), 2'-deoxyinosine, 2'-deoxynebularine, 6H, 8H-3,4-dihydropyrimido [4,5-c] oxazine-7-one or 2-amino-6-methoxyaminopurine.

71. The method of claim 51, further comprising substituting a methylated cytocine ('C) for a C in one or more CpG dinucleotide(s), if present in the oligo(s).

72. The method of claim 51, further comprising substituting by, or modifying one or more nucleotide residue(s) of the oligo(s) with, methylphosphonate, phosphotriester, phosphorothioate, phosphorodithioate, boranophosphate, formacetal, thioformacetal, thioether, carbonate, carbamate, sulfate, sulfonate, sulfamate, sulfonamide, sulfone, sulfite, sulfoxide, sulfide, hydroxylamine, methylene(methyimino) (MMI), methoxymethyl (MOM), methoxyethyl (MOE), methyleneoxy WO 00/62736 PCT/USOO/08020 323 (methylimino) (MOMI), methoxy methyl (MOM), 2'-O-methyl, phosphoramidate, C-5 substituted residues, or combinations thereof.

73. The method of claim 51, further comprising operatively linking to, or complexing the oligo(s) with, an agent selected from the group consisting of cell internalized and up taken agent(s) and cell targeting agents.

74. The method of claim 73, wherein the cell internalized or up taken agent is selected from the group consisting of transferrin, asialoglycoprotein, and streptavidin.

75. The method of claim 73, wherein the cell targeting agent is a vector, optionally a prokaryotic or eukaryotic vector.

76. A method of treating a disease or condition associated with a target selected associated with a disease or condition afflicting lung airways, comprising conducting the method of claim 56.

77. The method of claim 76, wehrein the amount of oligo(s) administered is (are) effective to reduce the production or availability, or to increase the degradation, of the mRNA, or to reduce the amount of the polypeptide present in the lungs.

78. The method of claim 77, wherein the amount of oligo(s) administered is (are) effective to reduce the production or availability, or to increase the degradation, of the mRNA, or to increase the amount of the surfactant present in the subject's lungs.

79. The composition of claim 4, wherein the oligo(s) is(are) anti-sense to the initiation codon, the coding region, the 5-end and the 3-end genomic flanking regions, the 5' and 3' intron-exon junctions, and regions within 2 to 10 nucleotides of the junctions of a gene(s) encoding an adenosine Al, A2a, A2b and\or A3 receptor, or anti-sense to the adenosine Al, A2a, A2b and\or A3 receptor mRNA.

80. The composition of claim 79, wherein all nucleotide linking residues are phosphorothioates.

81. The composition of claim 1, wherein the oligo is a DNA.

82. The composition of claim 1, wherein the oligo is an RNA.

83. The composition of claim 1, wherein the oligo comprises about 7 to up to about 60 mononucleotides.

84. The composition of claim 79, wherein the oligo(s) is selected from the group consisting of fragment(s) SEQ ID NOS: 1, 3, 5, 7, 8, and\or 11 through 2419, optionally wherein at least one mononucleotide residue is substituted or modified by methylphosphonate, phosphotriester, phosphorothioate, phosphorodithioate, boranophosphate, formacetal, thioformacetal, thioether, carbonate, carbamate, sulfate, sulfonate, sulfamate, sulfonamide, sulfone, sulfite, sulfoxide, sulfide, hydroxylamine, methylene(methyimino), (MMI), methoxymethyl (MOM), methoxyethyl (MOE), methyleneoxy (methylimino) (MOMA), methoxy methyl (MOM), 2'-O-methyl, phosphoramidate residues and/or combinations thereof.

85. The method of claim 51, wherein the oligo is administered topically to the airway, respiratory or pulmonary epithelium of the subject.

86. The composition of claim 1, wherein the oligo has a particle size of about 5-10 pm or in the range of 10-500 [m.

87. The composition of claim 1, further comprising a propellant.

88. The method of claim 50, wherein the oligo has a particle size of about 5-10 pm or in the range of 10-500 pm.

89. The method of claim 50, further comprising adding to the oligo a propellant.

90. The method of claim 51, wherein the oligo has a particle size of about 5-10 pm or in the range of 10-500 pm.

91. The method of claim 51, further comprising adding to the oligo a propellant.