AU6512699A

AU6512699A - Dna sequences for enzymatic synthesis of polyketide or heteropolyketide compounds

Info

Publication number: AU6512699A
Application number: AU65126/99A
Authority: AU
Inventors: Stefan Beyer; Helmut Bloecker; Petra Brandt; Paul M. Cino; Brian A. Dougherty; Steven L. Goldberg; Gerhard Hofle; Rolf-Joachim Mueller; Hans Reichenbach
Original assignee: Helmholtz Zentrum fuer Infektionsforschung HZI GmbH; Bristol Myers Squibb Co
Current assignee: Bristol Myers Squibb Co
Priority date: 1998-10-09
Filing date: 1999-10-11
Publication date: 2000-05-01
Also published as: JP2002527067A; WO2000022139A2; WO2000022139A3; DE19846493A1; CA2346499A1; EP1119628A2; WO2000022139A9

Description

WO 00/22139 PCT/US99/23535 DNA sequences for enzymatic synthesis of polyketide or heteropolyketide compounds The present invention relates to DNA sequences for enzy matic synthesis of polyketide or heteropolyketide compounds produced by the bacterium Sorangium cellulosum. Background and introduction This patent application describes DNA sequences for the enzymatic synthesis of polyketide and/or heteropolyketide structures synthesized by the myxobacterium Sorangium cellulo sum. Several of these compounds have known cytotoxic, immuno suppressive, antibiotic and fungicidal biological activity, with the epothilones having been most studied and character ized. The fermentation of large quantities of secondary me tabolites from microorganisms, especially from myxobacteria, is a time consuming and difficult process that often involves com plications (e.g. contamination, low product yield, difficult isolation and purification). Therefore it would be advanta geous to use a well-characterized organism for such fermenta tions. After cloning of the desired biosynthetic genes one could create such an organism via genetic engineering and ma nipulate the biosynthesis of the compound. Identified sequences WO 00/22139 PCT/US99/23535 2 can be cloned into optimized expression vectors and generate recombinant cell lines that overproduce polyketide structures. Polyketide synthases (PKS) and non-ribosomal peptide syn thetases (NRPS) represent macromolecular and multifunctional enzymes which are characterized by a modular architecture. PKS condenses activated carbonic acids (usually acetate and propi onate) and reduce the resulting 2-keto acid intermediates step wise in a fatty acid biosynthesis-like fashion. Responsible for each reaction step is a specific domain that recognizes, acti vates, condenses and reduces the carbonic acid. Depending on the presence of these domains in the corresponding modules, every reduction stage can occur in the final product (Rawlings, Nat. Prod. Reports 14, 523-556 [1997]; for a review, see Chem. Rev. 9.7, 2463-2760 [19971) . A typical example for the biosyn thesis of a polyketide is the macrolide antibiotic erythromycin (Staunton and Wilkinson, Chem. Rev. 97, 2611.-2630 [1997]). NRPSs are also modular enzymes and condense via peptide bonds amino acids to low molecular weight bioactive substances like bacitracin or tyrocidin. Typical domains of these systems acti vate the amino acid and condense it with the growing peptide chain. Methylations, epimerisations and modifications via addi tional protein domains are possible (Stachelhaus and Marahiel, FEMS Microbiol Lett. 125, 3-14 [1995]). Both types of enzymes (NRPS and PKS) share the modular organization of the proteins in which specific catalytic domains are responsible for recog nition, activation, condensation and modification of the single elongation units. The growing chain of amino acids and/or car bonic acids is extended through the action of one module adding one unit. The domains of each module carry the active centers responsible for the enzymatic steps of the biosynthesis.

WO 00/22139 PCT/US99/23535 3 Little is known about the biosynthesis of biologically ac tive polyketides and polypeptides from myxobacteria. Fragments of the biosynthetic gene clusters of soraphen and saframycin have been described from Sorangium cellulosum So ce26 and Myxo 5 coccus xanthus, respectively (Schupp et al., J. Bacteriol. 177, 3673-3679 [1995] and Pospiech et al., Microbiology 141, 1793 1803 [1995]) . We have constructed genomic libraries of the epothilone producer Sorangium cellulosum So ce90. Gene probes based on PKS and PS genes were used to isolate recombinant cos 0 mids, which were then sequenced and characterized. Several unique pathways containing PKS, PS, or a combination of both types of genes were identified, demonstrating that this organ ism is potentially a rich source of novel bioactive compounds. A subject of the present invention is therefore to provide 5 DNA sequences according to claim 1 the expression products of which perform or are involved in the enzymatic biosynthesis, mutasynthesis or partial synthesis of polyketide or hetero polyketide compounds. The DNA sequences may be inserted into well known and optimized expression vectors by commmon tech 0 niques of molecular biology, thus allowing transformation, se lection and cloning of cells, which cells are then capable of synthezising polyketide or heteropolyketide compounds by fer mentation. Using an overproducing clone allows the desired polyketide or heteropolyketide compounds be easily produced and 5 recovered in high amounts. Further, knowledge of the localiza tion of regulatory DNA segments and individual structural genes allows "site-directed mutagenesis" using common techniques for genetic engineering, and thus construction of optimized enzymes ("protein engineering") for fermentative synthesis of polyketi 0 de or heteropolyketide compounds.

WO 00/22139 PCT/US99/23535 4 The invention thus further relates to a recombinant ex pression vector according to claim 16, cells transformed there with according to claim 17 and to a process for enzymatic bio synthesis, mutasynthesis or partial synthesis of polyketide or heteropolyketide compounds according to claim 23. Preferred and/or advantageous embodiments of the present invention are subject-matter of the subclaims. In brief, the invention consists of (1) cloned Sorangium cellulosum polyketide synthase (PKS) and/or peptide synthetase (PS) biosynthetic cluster DNA and (2) the nucleotide sequence and predicted protein coding sequences of the cloned DNA. The invention can be used for, but not limited to, (a) increasing yields of PKS product in Sorangium cellulosum (e.g., by ampli fication or genetic modification of the epothilone gene cluster or its component parts), (b) increasing yields of polyketide and/or peptide synthetase product in a heterologous system by transfer of the corresponding gene cluster or its component parts, which may be followed by amplification or genetic modi fication of the PKS and/or PS gene cluster or its component parts, (c) modification of the polyketide and/or peptide syn thetase product chemical structure in either Sorangium cellulo sum or a heterologous host (e.g., by genetic modification of the corresponding gene cluster or its component parts) and (d) for the detection of genes and gene products involved in making polyketides or related molecules in other organisms (e.g., by hybridization or complementation assays). DNA sequence and analysis is presented for the following cosmids and plasmids: - A2 cosmid as defined in claim 6 - the pEPOcos6 region (overlapping of pEPOcos6 and pEPOcos7) as defined in claim 7 WO 00/22139 PCT/US99/23535 5 - pEPOcos8 cosmid as defined in claim 10 A5 cosmid as defined in claim 12 - Sau4 (10 kb plasmid) as defined in claim 14 The invention is now described in more detail by examples and for illustration only. The examples are not to be construed as any limitation of the scope. Figure 1 is a restriction map of one of the DNA sequences of the present invention (cosmid A2 insert) indicating also the localization of regulatory DNA segments and the individual structural genes ("open reading frames" or ORFs) 1 to 16. Figure 2 shows the open reading frames found on pEPOcos6 region DNA sequence data from A2 cosmid are as defined in claim 6. Table 1 correlates ORFs 1 to 16 found on A2 cosmid with the re spective biological function (Regulators, Enzymes).

WO 00/22139 PCT/US99/23535 6 Table 1 gene/function position ORF 1 regulatory element 1666 - 1 ORF 2 regulatory element 1605 - 3338 ORF 3 acyl-t-RNA synthetase 6100 - 3398 ORF 4 monooxygenase 7110 - 6374 ORF 5 amino transferase 9590 - 8433 ORF 6 L-dopa decarboxylase 11393 - 9855 ORF 7 oxidoreductase 13656 - 12712 ORF 8 polyketide synthase 15374 - 18984 ORF 9 polypeptide synthetase 20003 - 27889 ORF 10 peptidase 28251 - 29402 ORF 11 regulatory element 31720 - 30401 ORF 12 sigma factor 31982 - 32932 ORF 13 regulatory element 33128 - 33613 ORF 14 regulatory element 33661 - 34007 ORF 15 transcription regulator 35611 - 35255 ORF 16 signal transduction 37856 - 35730 WO 00/22139 PCT/US99/23535 7 Working Examples A. Construction of a Sorangium cellulosum cosmid library 1. Isolation of genomic DNA from S. cellulosum So ce90 a. Sorangium cellulosurn So ce90 was spread onto solid CA-2 agar and incubated at 30 0 C for 5-7 days. CA-2 agar is prepared by autoclaving 18 g Bacto-agar (Difco Laboratories, Detroit, D MI) in 800 ml dH 2 0 for 20 min at 121 0 C and cooling to 50-55'C in a water bath. The following filter-sterilized solutions are added to the agar: 20% (w/v) glucose, 50 ml; Solution A (7.5% [w/v] KNO 3 ,7.5% K 2

HPO

4 ), 10 ml; Solution B (1.5% [w/v] MgSO 4 7H 2 0) , 10 ml; Solution C (0.2% [w/v]CaCl 2 -2H 2 0,0.15% [w/v] D FeCl 3 ) , 10 ml; 1 M HCl, 1 ml; autoclaved 4-day old Sorangium cellulosum broth, 100 ml. A sample of cells was removed from the plates with a sterile loop and inoculated into 50 ml of G51t medium in a 250 ml Erlenmeyer flask. G51t consists of 0.5% starch (Cerestar) , 0.2% tryptone, 0.1% yeast extract, 0.05% D CaCl 2 , 0. 05% MgSO4-7H 2 0, 1.2% 4-(2-hydroxyethyl)-1-piperazine ethanesulfonic acid (HEPES), 0.2% glucose, pH 7.6. The flasks were shaken at 30"C, 160 rpm until a dense orange bacterial growth was obtained (ca. 5-7 d.) . The cells were pelleted by centrifugation at 6,000 x g and used immediately or stored fro 5 zen at -20 0 C. The protocol used for isolating chromosomal DNA from bac teria using hexadecyltrimethylammmonium bromide (CTAB) has been described previously (Ausubel et al., Current Protocols in Mo lecular Biology, John Wiley and Sons, New York, 1990) . The pre D citrated DNA was recovered with a bent Pasteur pipette, washed WO 00/22139 PCT/US99/23535 8 with 70% and 95% ethanol, air-dried, and resuspended in 0.5 ml TE buffer (0.01 M Tris-HCl, 0.001 M ethylenediaminotetraacetic acid [EDTAI, pH 8.0). 5 b. Alternatively, genomic DNA was isolated from S. cellulosum cells cultured as described in section A.1 using the Midi Qiagen Blood & Cell Culture DNA purification Kit (Qiagen, Hilden, Germany) following the Qiagen Genomic DNA Handbook pro tocol for bacterial DNA isolation (1997, Qiagen, Hilden, Ger 0 many, p. 29 ff.). In order to obtain high molecular weight chromosomal DNA the precipitated DNA was recovered with a bent pasteur pipette as described in section A.1. 5 2. Isolation of plasmid DNA a. pFD666: pFD666 is a bifunctional E. coli-Streptomyces cosmid cloning vector (see Denis and Brzezinski, Gene 111, 115-118 [1992]). To maintain stability of large inserts, it is present 0 in low-medium copy number when replicated in E. coli. For this reason, isolation of sufficient pure DNA to carry out cloning experiments was difficult using commercial kits with standard protocols. A modified procedure was therefore used to obtain pFD666 DNA. A 10 ml culture of DH10B(pFD666) was grown for 16 5 20 hr at 37 0 C in LB (1% tryptone, 0.5% yeast extract, 0.5% NaCl, pH 7.0) medium containing 50 pg/ml kanamycin sulfate. Fifty ml of LB + kanamycin was inoculated to a starting OD 600 of ca. 0.25 and shaken at 300 rpm, 37 0 C, until the OD 600 reached ca. 0.6. Five hundred ml of LB + kanamycin medium in a 2 1 0 flask was inoculated with 25 ml of this culture and incubated WO 00/22139 PCT/US99/23535 9 under the same conditions for 2.5 hr. Chloramphenicol ( 2.5 ml of a 34 mg/ml solution in 100% EtOH) was added and the incuba tion continued for an additional 16-20 hr. (The previous steps were performed according to Maniatis et al. Molecular Cloning: A Laboratory Manual, Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, 1989.) Cells were pelleted for 10 min, 16,000 x g . They were resuspended in 9 ml of 50 mM glucose/25 mM Tris-HCl (pH 8.0)/10 mM EDTA and transferred to a 50 ml disposable cen trifuge tube. One ml of a freshly-prepared 10 mg/ml lysozyme solution in 10 mM Tris-HCl, pH 8.0 was added and the cell sus pension incubated in a 37 0 C water bath for 10 min. Twenty ml of a freshly-prepared 0.2 NaOH/1% sodium dodecyl sulfate (SDS) so lution was added and the tube inverted gently 5-7 times to mix the contents. After 5 min at room temperature, 15 ml of 5 M po tassium actate (pH 4.8) was added and the tube inverted sharply 3-4 times. The tube was centrifuged at 6,000 x g for 10 min at 4 0 C and the supernatant poured though 2 layers of sterile cheese cloth into a fresh 50 ml disposable tube. Isopropanol to a final concentration of 0.6% was added and the contents of the tube mixed several times. The precipitated nucleic acid was centrifuged at 6,000 x g for 10 min at 4"C. The pellet was washed with 70% EtOH and any excess EtOH was aspirated from the pellet, which was allowed to air dry for 5 min. It was resus pended in 5 ml of 50 mM 3-(N-Morpholino)propanesulfonic acid (MOPS)/750 mM NaCl, pH 7.0 and added to an equilibrated to QIAfilter Midi column (Qiagen, Chatsworth, CA) . The manufac turer's protocol for washing and eluting the plasmid DNA was followed.

WO 00/22139 PCT/US99/23535 10 b. SuperCos: SuperCos plasmid DNA was purchased from Strata gene (La Jolla, CA). 3. Preparation of ca. 38-47 kb Sau3A1 fragments of S. cellulo 5 sum chromosomal DNA a. S. cellulosum chromosomal DNA prepared as described in sec tion A.1.a was partially cleaved with restriction endonuclease Sau3A1 in a 1000 yl reaction volume consisting of 50 pg chromo 0 somal DNA, 5 units enzyme (Promega, Madison , WI), 0.006 M Tris-HCl, 0.006 M MgCl 2 , 0.10 M NaCl, and 0.001 M dithiothrei tol (pH 7.5) for 5 min at 37 0 C. The reaction mixture was ex tracted once with an equal volume of 1:1 phenol:chloroform. After centrifugation, the upper aqueous phase was saved, to 5 which 0.1 vol. of 3 M sodium acetate and 0.6 vol. isopropanol was added. DNA was pelleted by centrifugation for 5 min at 16,000 x g in a microfuge and washed once with 0.5 ml 70% EtOH. After drying in a SpeedVac (Savant Instruments, Farmingdale, NY) for 5 min, the pelle: was resuspended in 0.1 ml TE buffer. 0 The DNA was layered ontoc of a 12 ml 10-40% sucrose gradient prepared in TE buffer and centrifuged at 113,600 x g for 16 hr, 10(C using a Beckman SW40Ti rotor (Beckman Instruments, Palo Alto, CA) . Five hundred gl aliquots of the gradient were re moved using a pipetor beginning at the top of the tube. Samples 5 (5 gl) of the fractions were analyzed by electrophoresis through a 0.5% agarose gel in TAE buffer (0.04 M Trizma base, 0.02 M acetic acid, and 0.001 M EDTA, pH 8.3) containing 0.5 pg/ml ethidium bromide for 6 hr at 100 V. Fractions containing DNA fragments of ca. 4C--5 kb were identified by comparison to 0 a high molecular weight DNA standard (Life Technologies, WO 00/22139 PCT/US99/23535 11 Gaithersburg, MD) . Sucrose was diluted from the corresponding 0.5 ml fraction by addition of 0.5 vol. TE. Subsequently, DNA was precipitated by addition of 0.1 vol. 3 M sodium acetate and 0.6 vol. isopropanol. DNA was pelleted by centrifugation at 16,000 x g for 10 min in a microfuge. DNA was washed with 0.5 ml 70% EtOH and dried in a SpeedVac with moderate heat for 10 min. Finally, the DNA was resuspended in distilled H 2 0 at a concentration of 0.5 mg/ml. b. Alternatively, 10 pg of S. cellulosum chromosomal DNA pre pared as described in A.1.b was treated with 0.3 U Sau3A1 (New England Biolabs, Beverly, MA) for 1 h at 370C in 400 pl of the supplier's recommended reaction buffer. Formation of DNA frag ments of about 40 kb in size was checked by comparison of the motility behavior with high molecular weight DNA standards af ter a 0.3% agarose gel electrophoresis. An equal volume of phe nol:chloroform (1:1) was added, mixed and centrifuged. The up per aqueous phase was recovered and 0.1 vol. of 3 M sodium ace tate and 0.6 vol. of isopropanol were added. After centrifuga ) tion, the precipitated DNA was washed twice with 0.5 ml 70% ice cold ethanol and finally air-dried. The DNA fragments were re suspended in 100 pzl shrimp alkaline phosphatase reaction buffer and dephosphorylated for 150 min. at 370C using 2 U shrimp al kaline phosphatase (Amersham Life Science, Cleveland, OH) . A phenol:chloroform extraction followed as described above. Fi nally, the DNA was precipitated by addition of 0.1 vol. 3 M so diuT acetate and 0.6 vol. isopropanol, dried, and dissolved in TE buffer.

WO 00/22139 PCT/US99/23535 12 4. Preparation of cosmid libraries a. Using pFD666: Vector pFD666 was cleaved with restriction endonuclease BamHI in a 0.02 ml reaction volume consisting of 2 pg plasmid DNA, 10 units of BamHI (Promega), 0.006 M Tris-HCl, 0.006 M MgCl 2 , 0.05 M NaCl, and 0.001 M dithiothreitol (pH 7.5) for 90 min at 37 0 C. Five pl of 10x alkaline phosphatase buffer (0.5 M Tris-HCl [pH 9.3], 0.01 M MgCl 2 , 0.001 M ZnCl 2 , 0.01 M spermidine) was added to the reaction followed by alkaline phosphatase (0.01 units/pmol ends; Promega) and distilled H 2 0 to a final volume of 0.05 ml. The sample was incubated for 30 min at 37 0 C and a second aliquot of phosphatase was added. Af ter a further 30 min at 37 0 C, .0.3 ml of stop buffer (0.01 M Tris-HCl [pH 7.5], 0.001 M EDTA, 0.2 M NaCl, 0.5% SDS) and 0.35 ml of 1:1 phenol; CHCl 3 was added to the reaction. The sample was mixed gently several times by inversion and centrifuged at 16,000 x g for 3 min to separate the phases. The aqueous layer was removed to a new microfuge tube. 0.1 vol. 3 M sodium ace tate and 2 vol. 100% EtOH were added and the precipitated DNA pelleted by centrifugation at 16,000 x g for 10 min. Liquid was removed by aspiration and the pellet washed once with 0.5 ml 70% EtOH. The DNA was dried in a SpeedVac and resuspended in TE buffer to 0.5 mg/ml. Digested, phosphatase-treated pFD666 was ligated to the partially-cleaved chromosomal DNA (see sections A.3.a and B.1.a) in a 0.005 ml reaction consisting of 1 pig pFD666, 1 pig S. cellulosum DNA, 0.03 M Tris-HCl (pH 7.8), 0.01 M MgCl 2 , 0.01 M dithiothreitol, and 0.0005 M adenosine-5'-triphosphate and 1.5 Weiss units of T4 DNA ligase (Promega) . The reaction was carried out at room temperature for 2 hr. The entire reaction WO 00/22139 PCT/US99/23535 13 mix was packaged into bacteriophage k in vitro using Packagene extracts (Promega) according to the manufacturer's directions. The entire packaging reaction (0.5 ml) was diluted with 4.5 ml SM buffer (per liter: 5.8 g NaCl, 2 g MgSO 4 .7H 2 0, 1 M Tris HCl[pH 7.5], 5 ml 2% gelatin solution). Transfection was per formed by adding 10 ml ci an overnight culture of E. coli DH5ca that had been grown in LB medium with 0.01 M MgSO 4 and 0.2% maltose to the diluted phage and incubating at 37'C for 20 min. 0.8 ml of LB was added and the cells shaken at 225 rpm for 1 hr at 37 0 C. Cells were pelleted, resuspended in LB, and spread onto a 150 mm LB + kanamycin agar plate. After 3 d. at 30 0 C, the colonies were harvested by picking ca. 800 colonies into 2.0 ml LB + kanamycin medium containing 20% glycerol, freezing on dry ice, and storing at -70 0 C. In addition, six kanamycin resistant colonies were inoculated into 2 ml LB + kanamycin liquid medium and incubated at 37 0 C, 250 rpm, for 18-24 hr. Cosmid DNA was prepared using a standard alkaline lysis proce dure starting with 1.5 ml of the culture. DNA was digested with restriction endonuclease PstI and samples electrophoresed on a 0.8% TAE agarose qel for 1.5 hr at 100 V. A unique restriction pattern was noted in each sample and the total size of the in sert was calculated to be between 40 and 45 kilobases. b. Using SuperCos: 30 pg of vector SuperCos was digested with XbaI (New England Biolabs, Beverly, MA) for 210 min at 37 0 C in 100 pl of the recommended reaction buffer. Ten pl sodium ace tate and 60 p/l isopropanol was added before the solution was centrifuged for 30 min 16,000 x g. The precipitated DNA was washed twice with 500 pL ice cold 70% ethanol. The vector DNA was precipitated and air-dried, dissolved in 135 l shrimp al- WO 00/22139 PCTIUS99/23535 14 kaline phosphatase reaction buffer and treated with 2.5 U shrimp alkaline phosphatase for 150 min. After heat inactiva tion of the enzyme at 75 0 C for 20 min, a phenol:chloroform ex traction was performed as described in section 1. c. The DNA, 5 resuspended in 100 pul BamHI restriction buffer was hydrolyzed with 15 U BamHI (New England Biolabs, Beverly, MA) for 180 min. A phenol:chloroform extraction followed (see section A.3). The SuperCos DNA was precipitated by additon of 0.1 vol 3 M sodium acetate and 0.6 vol isopropanol, centrifuged at 16,000 x g, and 0 resuspended in 50 pl TE buffer. Four pg of digested vector DNA was ligated with 10 pg par tially hydrolyzed genomic DNA from S. cellulosum (as described in section A.3.b) in a final volume of 20 pl using 2 U T4 DNA ligase and the appropriate reaction buffer (Gibco BRL, Eggen 5 stein, Germany) . The reaction was carried out at 16 0 C over night. The reaction mixture was packaged into phage particles using the Gigapack III XL packaging extract kit (Stratagene) according to the manufacture's protocol. Treatment of packaging reaction mixture and transfection of E. coli SURE (Stratagene) 0 was performed as described in 4.a. Transfected cells were con centrated by centrifugation, resuspended in fresh LB medium and distributed on LB agar plates containing 50 pig/ml-'kanamycin. The plates were incubated overnight at 30 0 C. 1600 recombinant clones were transferred into 96 well microtiter plates filled 5 with 80 pl LB medium containing 50 pg/ml kanamycin per well and propagated overnight at 30 0 C. The following day the microtiter plates were used to inoculate a second set of microtiter plates in order to obtain a duplicate of the recombinant clones. Each well of the original set of microtiter plates was supplemented 0 with 80 l 50 % glycerol and the entire plate stored at -70 0

C.

WO 00/22139 PCT/US99/23535 15 20 randomly chosen transformants were inoculated into 3 ml LB medium with 50 pg/ml- kanamycin and incubated over night at 371C in order to isolate plasmid DNA using the Qiagen plasmid extraction kit (Qiagen, Hilden, Germany) . Restriction fragment analysis of the recombinant cosmids using the restriction endo nucleases PstI and BglII indicated that the cosmids contained inserts of approximately 35 to 42 kb in size. B. Construction of a S. cellulosum plasmid library 1. Preparation of 8-12 kb fragments of S. cellulosum chromoso mal DNA. S. cellulosum chromosomal DNA prepared as described in sec tion A.l.a was partially cleaved with restriction endonuclease Sau3A1 in a 100 !iL reaction volume consisting of 5 pg chromoso mal DNA, 5 units enzyme (Promega, Madison , WI), 0.006 M Tris HCl, 0.006 M MgCl 2 , 0.10 M NaCl, and 0.001 M dithiothreitol (pH 7.5) for 4 min at 37"C. The digested DNA was electrophoresed through a 11 x 14 cm 0.8% TAE-agarose gel for 18 hr at 17 V. Fragments of 8-12 kb were cut from the gel and purified using the QIAquick Gel Extraction Kit using the manufacturer's proto col (Qiagen). 2. Preparation of the plasmid library Plasmid pZero2.1 (Invitrogen, Carlsbad, CA) was cleaved with restriction endonuclease BamHI in a 0.02 ml reaction volume consisting of 1 tg plasmid DNA, 10 units of BamHI (Promega), 0.006 M Tris-HCl, 0.006 M MgCl 2 , 0.05 M NaCl, and 0.001 M di- WO 00/22139 PCT/US99/23535 16 thiothreitol ( pH 7.5) for 20 min at 37'C. 0.08 ml of dH 2 0 and 0.1 ml of 1:1 phenol:CHCl3 was added. The sample was briefly vortexed and centrifuged at 16,000 x g for 2 min. The aqueous layer was removed to a new microfuge tube. 0.1 vol. 3 M sodium 5 acetate and 2 vol. 100% EtOH were added and the precipitated DNA pelleted by centrifugation at 16,000 x g for 10 min. Liquid was removed by aspiration and the pellet washed once with 0.5 ml 70% EtOH. The DNA was dried in a SpeedVac and resuspended in TE buffer to 0.004 pig/ml. Digested pZero2.1 was ligated to the D partially-cleaved chromosomal DNA in a 0.01 ml reaction con sisting of 0.004 tg pZero2.1, 0.05 tg S. cellulosum DNA, 0.03 M Tris-HCl (pH 7.8), 0.01 M MgCl 2 , 0.01 M dithiothreitol, and 0.0005 M adenosine-5'-triphosphate and 1.5 Weiss units of T4 DNA ligase (Promega) . The reaction was carried out at room tem 5 perature for 2 hr. 0.015 ml dH 2 0 and 0.25 ml of 1-butanol were added, the sample vortexed briefly, and centrifuged at 16,000 x g for 10 min. Liquid was aspirated away from the pellet and the sample dried in a SpeedVac for 5 min. The ligated DNA was re suspended in 0.005 ml dH 2 0 and mixed with 0.04 ml of electro competent Escherichia coli DH10B cells (GIBCO/BRL, Gaithers burg, MD) . The sample was placed into a pre-chilled 0.2 mm-gap electroporation cuvette and transformed into the bacteria by electroporation using a BioRad Gene Pulser II unit (BioRad, Hercules, CA) at 25 VF and 200 Q. 0.96 ml SOC medium (0.5% D yeast extract, 2% tryptone, 10 mM NaCl, 2.5 mM KCl, 10 mM MgCl 2 , 20 mM MgSO 4 , 20 mM glucose) was mixed with the cells and transferred to a 1.5 ml microfuge tube. The sample was incu bated at 37 0 C, 225 rpm, for 1 hr. Aliquots of the cells were spread onto an LB agar + kanamycin and incubated at 37 0 C for 20 D hr to estimate the number of transformants obtained. Six kana- WO 00/22139 PCT/US99/23535 17 mycin resistant colonies were confirmed to contain an insert of the expected size as described in section A.4.a. C. Identification of cosmids possessing polyketide synthase genes 1. Colony blot hybridizations using cosmid library in pFD666: A 20 x 20 cm sheeo of Duralon UV membrane (Stratagene) was placed on top of a 24.5 x 24.5 cm square bioassay dish con taining 250 ml LB agar - kanamycin. An aliquot of the frozen cosmid library in 1 ml LB medium was spread on the filter. The plate was incubated at 3720 for 24 hr. Colonies were replicated onto two fresh filters which were placed onto LB + kanamycin agar medium and incubated at 28 0 C for 18 hr. Lysis of cells and neutralization of released DNA was performed according to di rections that were provided with the filters. The DNA was crosslinked to the filters using a UV Stratalinker 2400 unit (Stratagene) in the auto crosslink mode. Cell debris was re moved by placing the filers in a container with a solution of 3 X SSC (20 X SSC contains, per liter, 173.5 g NaCl, 88.2 g so dium citrate, pH adjusted to 7.0 with 10 N NaOH), 0.1% SDS and rubbing the lysed colonies with a Kimwipe. The filters were then incubated at least 3 hr with the same wash solution for at least 3 hr at 65 0 C. The plasmid library was treated similarly except cells were spread onto a 137 mm circular Duralon UV mem brane placed on top of a 150 mm petri dish containing 80 ml LB agar + kanamycin. For hybridizations, a probe consisting of a 650-base pair (bp) polymerase chain (POR) fragment representing a portion of a S. cellulosum polyketide synthase gene was used. The fragment WO 00/22139 PCTIUS99/23535 18 was amplified using primers to consensus regions of Type I (macrolide) polyketide synthase (PKS) genes (Swan et al., Mol. Gen. Genetics 242, 358-362 [1994]) . A series of sense and anti sense oligonucleotides were prepared for PCR studies as indi 5 cated in the following table 2: Table 2 Oligo- I. DNA sequence (5'--> 3') Corresponding nucleotide amino acid sequence 120 CGGT (C/G)AAGTC (C/G)AACATCGG KSNIGHT (sense) 121 (anti- GC (A/G)ATCTC (A/G)CCCTGCGA(A/G)TG HSQGEIA sense) 122 GT(C/G)GACAC (C/G)GC(C/G)TGCTC(C/G) VDTACSS (sense) 123 GG(C/G)AC(C/3)AACGC(C/G)CACGT(C/G)A GTNAHVI (sense) T 124 (anti- CCCTG(C/G)CC C/G)CGGGAA(C/G)ACGAA FVFPGQG sense) 0 The selection of C or G where necessary in the third position of a codon reflects the very high overall G + C content of S. cellulosum (ca. 70%) . Conditions for PCR were as follows: 0.01 M Tris-HCl (pH 9.0), 0.05 M KCl, 0.003 M MgCl 2 , 0.1% Triton X 5 10C,.200 pM of each primer, 2.5 U Taq DNA polymerase (Promega), 5.0% dimethyl sulfoxide (Sigma), and 0.01 pg of S. cellulosum chrcnosomal DNA in a 0.0C5 ml reaction volume. Reactions were WO 00/22139 PCT/US99/23535 19 carried out in a Perkin-Elmer Model 480 Thermocycler (Perkin Elmer Corporation, Foster City, CA) under the following condi tions: 94 0 C, 1 min; 50 0 C, 1 min, 72 0 C, 1.5 min for a total of 30 cycles. Each possible combination of sense and anti-sense prim 5 ers were tried. A 650-bp and 350-bp fragment was amplified us ing oligos 120 + 124 and 123 +124, respectively. The sequence of the fragments were determined using the ALFexpress AutoRead kit to fluorescently label the DNA, which was analyzed on an ALFexpress sequencing apparatus (Pharmacia). The data indicated D both PCR fragments possessed significant homology to polyketide synthase genes of Type I antibiotics. The 650-bp fragment was chosen for hybridization experiments. The fragment was labeled with 32 P-dCTP using the NEBlot kit (New England Biolabs, Beverly, MA) and purified on a Bio-Spin 6 column (BioRad, Hercules, CA.). Duplicate blots were pre hybridized in 3 X SSC (1 X SSC contains 0.15 M sodium chloride and 0.015 M sodium citrate, pH 7.0), 4 X Denhardt's solution (100 X is 2% Ficoll [Type 4001 , 2% polyvinylpyrrolidone, and 2% bovine serum albumin [Fraction VI) , and 100 pg/ml sheared, de 3 natured salmon sperm DNA; all reagents purchased from Sigma Chemicals, St. Louis. The labeled DNA was heated in a boiling water bath for 5 min to denature the strands, cooled on ice, and added to the pre-hybridization solution. The filters were incubated for at least 18 hr in a roller bottle hybridization 5 oven. They were transferred to new bottle, then washed two times in 2 X SSC, 0.1% SDS at 70 0 C for 30 min (moderate strin gency) . The membranes were placed on Whatman 3MM paper to re move excess liquid, covered with Saran Wrap, and exposed to au-tradiography film (Kodak X-OMAT LS) with two intensifying WO 00/22139 PCT/US99/23535 20 screens. The cassette was placed at -70 0 C and developed at ap propriate intervals. Approximately 100 colonies were seen to have hybridized on the duplicate filters. Fourteen of these were isolated from the master plate and grown in 4 ml LB + kanamycin medium for 20-24 hr, 37 0 C, 250 rpm. Plasmid DNA was prepared using the standard alkaline lysis method and digested with restriction endonucle ase PstI. The digested DNA was electrophoresed on a 0.8% aga rose gel in TAE for 3 hr at 100 V. Fragments were transferred to Duralon UV using the VacuGene XL vacuum blotting unit (Phar macia) and the recommended alkaline denaturation protocol. Hy bridization with radioactively-labeled PCR fragment and washing were carried out as described above. Two prominent types of cosmids were observed; one contained PstI fragments of ca. 7.0, 5.0, and 1.1 kb (pEPOcos6 and pEPOcos7) that hybridized to the probe; the other type had fragments of ca. 6.0 and 3.6 kb (pEPOcos8 and pEPOcos13) which were homologous to the probe. Restriction analysis confirmed that cosmids showing identical hybridization patterns had identical or overlapping inserts. PCR reactions using primers representing consensus sequences of Type I PKS genes were performed using the isolated cosmid DNA as template under conditions described above, except ca. 0.01 pg of cosmid DNA was included as template. Cosmids pEPOcos6 and pEPOcos8 amplified the 650-bp fragment seen when oligonucleo tides 120 + 124 were used, while pEPOcos8 and pEPOcos13 sup ported amplification of an 1100-bp PCR fragment with oligos 122 and 124. The latter fragment was sequenced and confirmed to possess strong similarity to Type I PKS genes. These data con firm that the recombinant cosmids are related to each other and that all contain PKS-like genes.

WO 00/22139 PCT/US99/23535 21 2. Colony blot hybridizations of plasmid library in pZero2.1: A 137-mm circle of Duralon UV membrane was placed on top of a 150-mm containing 75 ml LB agar + kanamycin. An aliquot of 5 the plasmid library (representing ca. 2,000 recombinant colo nies) in 0.5 ml LB medium was spread on the filter. The plate was incubated at 37 0 C for 20 hr. Colonies were replicated onto two fresh filters which were placed onto LB + kanamycin agar medium and incubated at 37 0 C for 6 hr. The filters were proc 0 essed for hybridization as described in Section C.1. Out of 8 positive colonies detected, one contained a plasmid with a DNA region not encoded by either pEPOcos6 or pEPOcos8. This plas mid, called Sau4, was characterized in more detail. 5 3. Colony blot hybridizations of cosmid library in SuperCos: The recombinant E. coli clones from the microtiter plates (see section 4. b) were used to produce two identical sets of hybridization filters in order to identify cosmids carrying PKS and PS genes. The recombinant clones were spotted onto 2 sets 0 of 22 x 22 cm LB agar plates containing 50 pg/ml kanamycin. Each plate contained 384 clones therefore representing 4 micro titer plates. The clones were incubated at 30 0 C overnight. Af ter pre-cooling for approximately 3 h at 4 0 C, 20 x 20 cm Hybond N' Nylon membranes (Amersham, Braunschweig, Germany) were 5 placed onto the agar surfaces. After 2 min. the membranes were removed and placed for 15 min. on Whatman 3 MM paper (Whatman paper Ltd., Maidstone, England) soaked with denaturation solu tion (0.5 N NaOH, 1,5 M NaCl) before they were transfered onto Whatman 3 MM paper saturated with neutralization solution (1 M 0 Tris-HCl, pH 7.5, 1.5 P NaCl) . Subsequently the membranes were WO 00/22139 PCT/US99/23535 22 placed onto Whatman 3 MM paper soaked with 2 X SSC (0.3 M NaCl, 0.03 M sodium citrate, pH 7.2) for 10 min. The membranes were baked for 40 min at 8 5 0C. Then, each membrane was overlayed with 5 ml Proteinase K solution (2 mg/ml Proteinase K in 2 x SSC) and incubated at 37 0 C for 90 min. Finally, cell debris was removed by wiping the membranes with a Kimwipe pre-wetted with 2 X SSC. As we were seeking in particular to identify biosynthetic pathways containing both PKS and PS genes, the following hy bridization strategy was taken: The screening was initially fo cused on ketosynthase domains from type I PKSs and on the ade nylation domain from PSs. Target-specific primers were used to amplify DNA fragments of the corresponding genes from chromoso mal DNA of S. cellulosum by PCR. The fragments obtained were then cloned, sequenced and the deduced amino acid sequence com pared to known ketosynthase and adenylation domains of PKS and PS, respectively. In a second step these PCR fragments were used as gene probes to detect recombinant cosmids of the S. cellulosum cosmid library. Oligonucleotides based on conserved amino acid sequences of ketosynthase domains from various type I PKS were optimized for myxobacterial DNA by comparison to a known myxobacterial biosynthetic gene cluster (Schupp et al., J. Bacteriol. 177, 3673-3679 [1995]) resulting in primer KS1Up (5 C/A)GIGA(A/G)GCI(A/C/T) (A/T)I(C/G) (C/A)IATGGA(C/T)CCICA(A/G)CAI (A/C)G-3') and KSEI (5'-GG(A/G)TCICCIA(A/G)I(G/C) (T/A)IGTICCIGTICC(A/G)TG-3'). PCR-primers TGD (5' T(A/T) (C/T)CGIACIGGIGA(C/T) (C/T) (G/T)IC(G/T)ICG-3') and WO 00/22139 PCT/US99/23535 23 LGG (5 A (A/T) IGA (A/G) (G/T) (G/C) ICCICCI (A/G) (A/G) (G/C) I (A/C) (A/G) AA (A/G ) AA-3') directed to genes encoding adenylation modules have been de scribed by Turgay et al. (Pept. Res. 7, 238-241 [1994]). PCR reaction mixtures with a final volume of 25 pl contained 0.1 pg template DNA, 0.2 U Taq DNA-po.lymerase (Gibco BRL, Eggenstein, Germany), 5 pumol dNTP, 5% dimethyl sulfoxide (Sigma), 1.5 mM MgCl 2 , 25 pmol of each primer and the appropriate reaction buffer supplied by Gibco BRL. Chromosomal DNA of S. cellulosum was used as template. Additionally, chromosomal DNA of Myxococ cus fulvus was used with PS primers. Reactions were carried out in an Eppendorf Mastercyler Gradient (Eppendorf, Germany) using the following conditions: denaturation 30 s at 97 0 C, annealing 30 s at 55 0 C, extension 60 s at 72 0 C for a total of 30 cycles. The formation of ca. 700 bp fragments using the KS primers and of ca. 350 bp fragments with the PS primers were confirmed by 0.8% agarose gel electrophoresis. Fragments of independent PCR reactions were ligated into vector pCR2.1TOPO using the TOPO TA Cloning kit (Invitrogen, Leek, The Netherlands) according to the manufacturer's protocol and transformed into E. coli XL1 Blue. Sequencing of the resulting plasmids and analysis of the deduced amino acid sequence revealed three different KS frag ments, designated pMOO8.4, pMOO8.6, pMOO8.7, one PS fragment (pAPs1) corresponding to S. cellulosum and one PS fragment (pDPsl) obtained with chromosomal DNA of M. fulvus. The PCR fragments were re-isolated by digestion with EcoRI from the plasmids pMOO8.4, pMOO8.6, and pM008.7, labeled, pooled and used as gene probes in hybridization experiments as described WO 00/22139 PCT/US99/23535 24 below. The same procedure was performed with the PS fragments of pAPs1 and pDPsl. Hybridization with PKS and PS specific DNA probes (see above) was carried out using the DIG nonradioactive labeling and detection kit (Boehringer Mannheim, Germany) and performed according to the supplier's manual using buffer containing 50% formamide. The membranes were hybridized in plastic bags con taining approx. 10 ml of hybridization solution at 39cC over night. Unspecific binding of probes was removed by 2 wash steps with 2 x SSC, 0.1% SDS at room temperature for 20 min. and one stringent wash step with 0.5 x SSC, 0.1% SDS at 60 0 C for 20 min. Detection of hybridizing DNA fragments was performed with the above mentioned system according to the manufacturer's pro tocol using CSPD as chemiluminescent substrate. The signals were recorded by exposure of the treated membrane to Hyperfilm ECL (Amersham Life Science, Little Chalfont, England) which was developed in appropriate time intervals. 71 signals were detected with the PKS specific gene probe. On the duplicate filters 35 signals were obtained with the PS specific gene probe of which 7 were already known from the PKS hybridization experiment. These recombinant cosmids harbored PKS- and PS-encoding genes. In order to corroborate these re sults PCR experiments were performed with DNA of the 7 recombi nant cosmids as template and PKS (KSlUp, KSD1) and PS specific primers (TGD, LGG) generating fragments of the expected size of approx. 700 bp and 350 bp, respectively (primers and reaction conditions see above). A comparison of the restriction fragment patterns of the DNA from the 7 recombinant cosmids carrying PKS and PS genes digested by BamHI facilitated an arrangement of the cosmids in WO 00/22139 PCT/US99/23535 25 3 groups. They were represented by cosmids designated A2 and A5. The remaining group was represented by pEPOcos6. Therefore, A2 and A5 represented good candidates for further DNA sequence analysis because they carry both PKS and PS genes. D. Random "shotgun" sequencing of recombinant cosmids and plas mids 1. Library construction a. pEPOcos6, pEPOcos8, A5, and Sau4: pEPOcos6 and pEPOcos7 were sequenced to completion, and contiguous sequence data and analysis for these overlapping cosmids is presented below for the "cos6 region" (cf. claims 7 and 9) . Sequencing of cosmid A5, pEPOcos8 and plasmid Sau4 was taken to the point of large contiguous sequences (contigs) representing the S. cellulosum insert; sequence and analysis presented below (cf. claims 10 to 15). Randomly sheared libraries were constructed for cosmids and plasmids of interest using a protocol similar to that of of Fleischmann et al., 199E (Science 269, 496) and modified in Fraser et al., 1995 (Science 370, 397). Briefly, Qiagen-column purified cosmid DNA (-10 pg) was sheared to a size of approxi mately 2 kb and the DNA end-repaired using BAL31 nuclease. The DNA was gel-purified after electrophoresis through a 0.75% low melting temperature agarose gel containing 0.5 pg/ml ethidium bromide in 1X TAE buffer run at 80 V for 2 hours. The volume of the low-melt agarose gel slice was estimated by adding the gel slice to a microfuge tube and weighing, then 0.1 vol. of 3 M sodium acetate (pH 7) was added and the agarose incubated at 60 0 C. The temperature was equilibrated to 37cC, and DNA ex- WO 00/22139 PCT/US99/23535 26 tracted twice using an equal volume of buffered phenol (Life Technologies). The aqueous phase was transferred and extracted once with an equal volume of chloroform, then ethanol preci pated by the addition of 2 vol. cold 100% ethanol. DNA was con 5 centrated by spinning at 16,000 x g in a microcentrifuge. The DNA pellet was washed with 1 ml 70% ethanol and resuspended in 100 pl of 0.1X TE. The DNA was ligated to SmaI-digested, phos phatase-treated pUC18 vector (Pharmacia), and single insert re combinants isolated by gel-purification of the band containing vector plus a single insert, followed by T4 polymerase polish ing, and a final intramolecular ligation of the vector-plus single-insert DNA. This final ligation represents a library of highly random ca. 2 kb fragments that was used for shotgun se quencing of the ca. 40 kb cosmids or ca. 10 kb plasmids. b. Cosmid A2: Cosmid DNA with inserts of S. cellulosum was isolated by an alkaline lysis procedure and purified with Ma cherey Nagel columns (Machery und Nagel GmbH und CoKG, Dfren, Germany) using manufacturer's recommendation. Purified Cosmid D DNA was sonicated, end-repaired using T4 DNA Polymerase (Boe hringer Mannheim, Germany). After gel-purification fragments of a size of approximately 2 kb were ligated into SmaI-digested, phcsphatase-treated pTZ18R vector (Pharmacia). The ligation represents a library of highly random ca. 2 kb fragments that 5 was used for shotgun sequencing of the ca. 40 kb cosmid. 2. Sequencing and assembly *a. pEPOcos6, pEPOcos8, Sau4, and A5: DNA (1 pl of 100 pl total in the library) was transformed into E. coli by electro 0 poration (20 pl of Electromax DH10B cells from Life Technolo- WO 00/22139 PCT/US99/23535 27 gies) and cells spread onto LB plates containing 50 pg/ml ampi cillin. After growth overnight at 37 0 C, transformants (ca. 300 3000 CFU total) were tranfered to 96-well growth blocks and shaken overnight at 37 0 C in 1.3 ml LB medium with 50 pg/ml am picillin. Templates were prepared from these cells by an alka line lysis procedure (Qiagen QiaQuick Turbo Prep) to yield pu rified, double-stranded plasmid DNA. Cycle-sequencing of the plasmid templates was performed using universal forward and re verse primers and BigDye Terminator sequencing kits (Applied Biosystems), using the manufacturer's recommendations, then re solved using an AB1377 automated sequencer. Sequences were ed ited using Phred, then assembled into larger contiguous se quences using Phrap (Phil Green, University of Washington, St. Louis, MO). b. Cosmid A2: DNA (1 tl of 20 tl total in the ligation) was transformed into E. coli DH10B by electroporation and cells were spread onto LB agar medium containing 50 mg/ml ampicillin. After growth for 18 hr at 37 0 C, transformants were transferred to 96-well growth blocks and shaken overnight at 37 0 C in 1.3 ml 2x YT medium with 50 mg/ml ampicillin. Templates were prepared from these cells by an alkaline lysis procedure (Qiagen Qia quick Turbo Prep) to yield purified, double-stranded plasmid DNA. Cycle-sequencing of the plasmid templates was performed using universal forward and reverse primers and Big Dye Termi nator sequencing kits (PEBiosystems) or Thermo Sequenase fluo rescent labelled primer cycle sequencing kit (Amersham Pharma cia Biotech) using the manufacturer's protocols. In the shotgun phase of a cosmid, identical amounts of samples were sequenced either by dye-primer or dye-terminator chemistries (Pharmacia, PE Biosystems). Data were collected using Licor and ABI 377 WO 00/22139 PCT/US99/23535 28 automated sequencers and assembled with the GAP4 program (Bon field, Smith, Staden, Nucl. Acids Res. 23, 4992-4999 [1995]). Gaps were closed using custom made primers (MWG-Biotech) on plasmid templates or PCR products in combination with dye terminators. E. Bioinformatic Methods 1. Open reading frame (ORF) identification ORFs were identified in the pEPOcos6 region using the OMIGA 1.1.2 (GCG 0.4D) program from Oxford Molecular Limited. Default values were used (Standard genetic code, all ORFs over 50 bases) to generate ORFs; analysis of these results lead to the list of 14 highest quality ORFs as defined in claim 9. Other ORFs, genes, or genetic elements may be found in the pEPOcos6 insert that have not ye: been annotated. In addition to hand editing of the OMIGA-generated data, the MAGPIE automated ge nome analysis tool: (http://qenomes.rockefeller.edu/magpie/magie.html) was used to identify genes for all the sequenced cosmids and plasmids. ORFs identified in this manner are presented as both nucleotide and peptide files below. For cosmids A2 and A5, ORFs have been identified within the DNA sequences of A5 (contigs 10, 11, 12) and of A2 using the FramePlot analysis program from Ishikawa and Hotta (FEMS Microbiol. Lett., 174, 251-253 [1999] public available under [http://www.nih.go.jp/-jun/cgi-bin/frameplot.pl] which is based on positional base preference in codons typical for organisms having genomes with a high G + C content (Bibb et al., Gene 30, WO 00/22139 PCT/US99/23535 29 157-166 [1984]) Default parameters using ATG and GTG as start codons were used. The deduced amino acid sequence of predicted ORFs were compared with protein databases (GenBank, CDS trans lations, PDB, SwissProt, PIR, PRF) using BLASTP (Altschul et al. , Nucleic Acids Res. , 25, 3389-3402 [1997]) . Additionally, high scoring amino acid sequences were analyzed using the Pfam program [http://www.sanger.ac.uk/Software/Pfam/], which identi fied specific domain structures of the submitted proteins (Bateman et al. Nucleic Acids Res., 27, 260-262 [1999]). 2. BLAST searches BLASTP2 similarity searches were performed using the peptide files from the above ORE identification strategy as query se quences. Searches were performed using the in-house Bioinfor matics BLASTP2 (Version: BLASTP 2.Oal9MP-WashU) web page at the Bristol-Myers Squibb Pharmaceutical Research Institute (allows BlastN2, BlastP2, BlastX2, TblastN, and TBlastX searches) . In addition, peptide files generated by the MAGPIE analysis were automatically searched using a FASTA algorithm. 3. Best match and probable identification Analysis of the BLASTP2 and FASTA output led to an assign men- of a best match and probable function. The best match was usually the top scoring r-atch, although sometimes another match was given because it was a more relevant homolog, or no match was found with a significance greater than >e-4. Probable func tion represents the bes: estimate of function given the initial analysis of the BLAST dara and the published literature regard inc the best match, and may not necessarily represent the true function of the gene product (hypothetical proteins are of un- WO 00/22139 PCTIUS99/23535 30 known function) . A higher probability score indicates a higher liklihood that the probable function corresponds to that of the best match; e.g., the polyketide synthase matches are all above e-100, and given the very high significance scores are presumed to function as polyketide synthases (as are the high scoring peptide synthetases). The following is a summary. of the sequence data from the pEPOcos6 region, pEPOcos8, A5, Sau4 and A2. a. Data from pEPOcos6 region: Summary: A large PKS/PS cluster spanning multiple cosmids. An IS element (designated IS-Scl here) is found in the cluster - this may be a potential tool for genetic analysis of Soran glum. Statistics: Sequence was assembled from over 2000 random sequences (forward and reverse reads of the ca. 2 kb cloned fragments derived) 47,713 nucleotides of contiguous sequence (no pFD666 vec tor included) DNA sequence data are as defined in claim 7. Note: pEPOcos6_ORF7 sequences (cf. claim 9): the predicted N-terminus of ORF7 shows 145 nucleotide overlap with ORF6. Note: pEPOcos6_ORF8 sequences (cf. claim 9): >pEPO cos6_ORF8.seq ("ORF9_up" in Fig.2) WO 00/22139 PCTIUS99/23535 31 67.3% G+C Table 3 shows ORF data summary. Note: pEPOcos6_ORF1.seq is truncated at its 5' end; correspondingly pEPOcos6_ORF1.pep is truncated at its N-terminus. b. Data from pEPOcos8 region: Summary: Two PKS genes found on a cosmid. A Tn1OOO inser tion is also found (occurred during E. coli propagation) . No peptide synthetase genes were found; one P450 hydroxylase was identified. Statistics: 1952 random sequence reads from the pEPOcos8 library were assembled using phrap, with 1024 of the sequences assembling into 57 contigs. 12 of these contigs were chosen (totaling 56,537 bp) which each contained >6 reads and con sisted of about 1000 bp or more. The sequences of these 12 contigs and the associated ORFs are given below. DNA sequence data from contigs are as definded in claim 10. Table 4 shows more data. pEPOcos8 protein data are as defined in claim 11, i.e. for selected ORFs (polyketide synthase, peptide synthetases, or ORFs with high similarity to known genes).

WO 00/22139 PCT/US99/23535 32 C. Data from cosmid A5 insert: Summary: A cluster of PKS and PS genes found on the cos mid. Other genes possibly involved in this secondary metabolite production include a downstream lipoxygenase gene higly similar to eukaryotic orthologs. Statistics: 880 random sequence reads from the A5 library were assembled using phrap, with 530 of the sequences assem bling into 12 contigs. 3 of these contigs were chosen (totaling 41,556 bp) which each contained >100 reads and consisted of about 9000 bp or more. The sequences of these 3 contigs and the associated ORFs are given below. DNA sequence data from contigs are as defined in claim 12. Table 5 shows more data. Protein sequence daca from selected A5 ORFs are as defined in claim 13. d. Data from plasmid Sau4 insert: Summary: Insert contains PKS genes on two large contigs most similar to the soraphen PKS gene from Sorangium. Statistics: 565 random sequence reads from the Sau4 li brary were assembled using phrap, with 84 of the sequences as sembling into 18 contigs. 2 of these contigs were chosen (to taling 6596 bp) which each contained >10 reads and consisted of WO 00/22139 PCT/US99/23535 33 about 1000 bp or more. The sequences of these 2 contigs and the associated ORFs are given below. DNA sequence data from plasmid Sau4 contigs are as defined in claim 14. Table 6 shows more data. Protein sequence data from selected plasmid Sau4 ORFs are as defined in claim 15. e. Data from cosmid A2 Table 7 shows ORF data summary F. Construction of suitable recombinant expression vectors 1. Expression in Myxobacteria Heterologous expression of the ORFs shown in Figure 1 is performed by using a derivative of plasmid pSUP102 (Simon, R., Priefer, U., Pahler, A., Methods in Enzymology (1986), vol. ) 118, pp. 643-659). In this plasmid the gene for chloramphenicol resistance is changed for a cassette comprising the gene for streptomycin resistance and the promoter element of the Tn5 transposon. Short homologous genomic DNA segments from the host organism are ligated with the DNA sequences of Figure 1 and * with efficient regulatory elements into, for example, the EcoRI restriction site of the vector. Following amplifiction of the vectors in Escherichia coli the DNA is transfered by electropo ration of the host cells or by conjugation with Escherichia coli S17-I (Simon, R., Priefer, U., Pihler, A., Biotechnology ) (1983) , vol. 1, pp. 784-791) .

WO 00/22139 PCT/US99/23535 34 By means of the tetracycline or streptomycin resistance, respectively, mediated by the vector the host cells are checked for integration of recombinant plasmid DNA into the chromosome by homologous recombination. 2. Expression in Streptomyces cells Heterologous expression of the ORFs shown in Figure 1 is performed by using bifunctional Strepomyces-Escherichia coli cosmids pKU206 and pOJ466. D 3. Expression in Escherichia coli cells Heterologous expression of the ORFs shown in Figure 1 is performed by using "bacterial artificial chromosomes", cosmids (for example Supercos, Stratagene GmbH, Heidelberg) and T7 ex pression systems (Stratagene GmbH, Heidelberg; New England Bio labs Schwalbach, FRG). Expression of recombinant enzymes occurs in Escherichia coli cells constitutively expressing phosphopan tetheinyl transferase required for the formation of holoenzyme polyketide synthetases and polypeptide synthetases.

WO 00/22139 PCT/US99/23535 35 0 CD; a4) E-4 a) w 'U ) w w) a ai w M) In ~ 0)W w H ~ V? ( 4j 4 MU 4J A.J .0 41 c (o 7) 'U mU m i 1 . rw 0 mo V)o 0 - o~ o o o 0 0 C mC .4 =U . 0 w) 4-4 W 4 WU Cl) - -4 -4 '-1 &0) En ) C ( 0 4.J 4-4 - - 1 aJ J -- 4 -14 * -4 -,4 ) (I -4 .4 L U 0 4 4 i 4-) a) 4.) 41) 4.) mIf -Li W). - e -Nd -4 -4 4-4 0 >9 0. 4-) 0. A -- 4 9 l Q -4 -4 r. -4 -4 '-4 L)U a) ~ > 0 0 0) 09 0 0 u 0) m4 Q, (v J-- L 0. Q4 U~~aa 00. a 0 ) r- I -4 0 C). (N N dr .-4 ko -" l) - C - - 0 C- N -4 - N 4 -4 r. M C C) E ) I 1 1 -I 4 C -4 D ( -4 U C) a) o' (D CD -D (v a) w w a -4 -1 * . q a) E- ) N u U 4 -4 ) 0 .4 0 4 U U( o I -C kv r I I I 1~ f -4 C r-4 ~ I oE-1 l) r 0: 03 0 C) ON - C o 0% C)) r 0 m =) Cl ) C, C)~C) 4- 0 t, ->. C>4 Ci >. C. Ca -'Q r" If) co (N (Z: rn '. C: .00 0 kv. , . n - L , 0 i -4 L n en CN a)loc C'. I-f) c- ~~0 ~ '' ~ 0~ Cl I - a)V Lo eq 'U .r r c 4 .- 4 .- 4 .n-4 (N f -I cn wD r- ":P 0 J m CD - ~ 0) ko r- 04 6n =% C-) CD t co - -I v) C- Cl ( N 0- 1-4 Q,_ C 4~ ~ 0 U CS) L-4 m- 1- r- m4 4 ' 0 N C') (n' C) In , n M V, C l CD 11 - I 1 C 11 (U - 4 p . 0 04 -n 0D t qM I D '-o LM) C') 1. ( .1 -m( -~ . U D C - r - ' .4 - -4 -4 -4 ,-4 .4 C'-. C... C..i C~ C~ Z C.. C.. ~ C. C. C.-. C~en C-.~~~c cm00 0 00 0 0 0 WO 00/22 139 PCT/US99/23535 36 -4 a.' x .- I LO 0 4-j a) Li 0 .- 00 00 44.) 4-4 C.) 0 4 0 0 4 I41 a)M 4-, " -4 w O4 t. 41 -) 04 00 M) 0 WO 00/22 139 PCTfUS99/23535 37 .H -W CL + C) d), -H cn m 4 -J : -4 ~4 P4 W~ CL q CD -4 r-0 ini 0) 00 di . . CM rq C'j al~~c; -*-4r r C-4~~~~~C 01 CN C > o C 414 m~ r--4 C cv C') C,4 ' Go (D C) C) m. I-n t74 C--I .- 1 -4,~ WI ~ -,4 0 0 0 4d 4- d J-) '.d C- 4J4 0- 0 ' 0 0' ' 0' 0' 0 L) ~-- -- ) -4 U.. -H U- c_ -H U L WO 00/22139 PCT/US99/23535 38 C)Z 0 0 0 Inu C)D 0= , n 4r 0n m L - q Q nc 0 Cj C -7 - -W 4 -i r- i 17"cn _4 . N " - M - 4 M U 0N % l lL J-ID %0 C4 0 9 ul r- C n - m c N 4 ) f ~ Ln %0 C cn 0 r -4 l ) r-0U , C, C n M - n L w co o 40 to ~ d4 Cl(N In MN CD -j M UN 4 -~-m 'r "W .- 4 U~~I ' N 6 1 0 C ~ ) Ln LM 1-4 11 M 11 M N Mi C" (9n U , "r CD CD -I I o, In cn dn (.9 In L o~ Lo LM u- U M £ n r- tJ n V. 0 tul t7) M t.9 (N 0, 0, a% -~ 0 0N a, dm 0 a, .. 4 - ,.4 -4 .,1 ., 4- - 4 -4 --- 4- 1 " o. oN (N 0 4 I ~ 0 0 ', o 4 0~ WO 00122139 PCT/US99/23535 39 Table: 5, A5 assembly analysis summa=Y (continued) a. pEPOcos8 assaniblies CL 0 : OdJ CL ITgw. , 04gi CU' a~~C d)CD, CU Q , 0 Gy a)21, C CC cu.C E- r-8 c (0~ d2;E CL)~ ~ E E 0 0 CI ) Li~-~ =O irt r C o r 4 CD CL M CJN-: - - n -M L -U an go C:) uI C- 0 CD 0. -M I)o gi co ~ cw C CD LO va in CO CD - ~ ; N I ~C -CJ f C) - n %N co LO ) W3 W)0 C-4 W01) L) cc -- gn .r t

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.) C . w r 0c OdU WO 00/22139 PCT/US99/23535 40 .JJ --- 4 44 04 -- H 0~ --4 ) 44 En U r, k LA %0 r" U. -) 0 ~ r7 W m L 41 W >4 -4 o c q = Ln - Dtl C . -4 MH kO m) r- L0r n -, c m wm o 4 r ) = 6 = o = m m 5I n <n a -r to c A L n c a) CN 0 0- r o % - r l c - c " o v t .0 (=. (= C 3 C 4 1 - 4 c v c N cl Dc ) C a) 1- - 1 1- -4 1-- - 4 -4 -1 -4 -' -- -4 -4- 4 q 4- -1 I JJU, 4- A 4- - 4-J4) - 4 4 4 -W IA 0W -W -J 4J 41 tO L w~ 0 0 U 0 -' t 0 0N t 0 LA 0 0 . r- 0- 0 0 a 0 (N h- 0 0 u u uN -4 u u4 uo u- uA u ~ u- U u u' u u u WO 00/22139 PCT/US99/23535 41. cuJ 4) 0 a) Mn C d)) -4 --4 -J -J >9 04 ,4

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-4 En V) C-4 0~ C4 0m 0K L (14 m- a,*d ko a) Z) r 4 - *4 10 c o 4) - n -z co4 r" " - ) r- -4. 4 m. -- r- r-t -V, C .. m 4)c .r t o r r n : -4 4 N 0z m04.4 4 a 4 C) U- n L - 0L o~4 r ' n 4 ~ ~ t C:) LM C (NO L 1 N% 4 C 1 m D O IC N 5*) 4 kn a% m r - en0 ~ tz 'A r, (N u- ko 0 ON L NV U, 0M 05 (M LO =N 0- %0 r- M f o r a n o m c - o M ui 0 a' s-m c' 0'~~C m v m* %a r- t~ u - 5 ~(' ' 5 0 2 3- 0 2- ' m~~~~~~ -4 '. N 5) ( . o ~ .4 c - -4 "1 -4 (N eq 02 '3 (N4 s-4 -4 C-4 02 C5 c 2 sS t - .1 ~ 1 . 0 .4 ,- C5 S C , CD4 s-S~~ ~ 0 I. C1 0N CV CVt , .4 0 . sS U 4 0 sS t Q - N ( . s-4 -4 0 U 2 ( -1 4. -4 (N s-S q0 "0 "N N -2 -4 4O r-4 -N -q s 4 '1 m t7 t7 mN C) 3- - , '.0 (0 c U' M 2 020D, t3, 6 t 0n tm tDN 0m o0 0 r ' (0 U .07%02 sS s- - ,I '4 -4 -4 N , U -4 .,q -14 -4 . -4 - r-I , - "1 A. r .. q U, 0 ~ 0 '0 44 -- -4- -4 -1 -4 -4 U' 4.0 42 4J Ad A. 0 2 0 5-4 '-4 (N (N ~. - 0 0 0 0 o 0 Q- ~ , - - - -i ( N ( N ( o00000000 0 0 0 0 0 0 0 0 0 0 u 0 u u u u ciuuuUuuL WO 00/22139 PCT/US99/23535 42 ov cn~ e.W m c~ -4 C-4 -' 0 c4 _4.- -q~ r- 'a m -I C, 0 rC=C -4 M 4 1-4 4 4 M 0 M 6n 0,- m M, 0 0 00 0 a WO 00/22139 PCT/US99/23535 43 Q W ) a) 4J -4 - , .HI M) o n 0 0 = Ln en M ( 1 cl - 4 "4 a) . U-1 co4 to -4 Hd U, 0) -4 -4 -1 a)t -4 -1 E-4 L( LN N '..

WO 00/22139 PCTJUS99/23535 44 Table: 7. ORF data slunay f ram A2 insert E E r M0 (6 0 CZ) 0 mc CD 00 .0 c0 CFo- C~ ca an a Cj..L C -) Cl, 00 C - 0 ~(.J CV co C, 4 ca CQVU cu CU CU CU Cl) Q) co t M WV o a coC C m w c J O c OV ~Ci-4 0 2 0' ~C V) C )4 C i- G Cd) m Wo n ) tu r U -4 J t 0 ) 0 N CU a) M= en p- 0) - -o - m - .- L .0 C '' !%lo to -U, mN CD. 0) C ev r*O IwC cj- CI D 0 0 SOE~ C%4 C- .)C" a ES 0 E rn EiC u~L uDC ' 0 0 r'. CD' U' OI-C, r en 02 ) CD c A A cc C.) Lr C2 en - r L n V7 4MO -I g~ W C-4 CD). r D "C;9 V o cm - (N (Nq cn MmV LL 0

Claims

1. DNA sequence, the expression products of which cause an enzymatic biosynthesis, a mutasynthesis or a partial synthesis of polyketide or heteropolyketide compounds or are involved therein.

2. DNA sequence according to claim 1, wherein the polyketide or heteropolyketide compounds are epothilones.

3. DNA sequence according to any of the preceding claims, wherein the DNA is derived from myxobacteria.

4. DNA sequence according to any of the preceding claims, wherein the DNA is derived from Sorangium strains.

5. DNA sequence according to any of the preceding claims, wherein the DNA is derived from Sorangium cellulosum.

6. DNA sequence according to any of the preceding claims, wherein the DNA is selected from the group consisting of: (a) the following DNA sequence: Seq ID No 1 (A2 cosmid) GGATCGCGGCGCCCTCGCGCTGCTCCTCGAGCGTGCGGAGGAACTCCCACGCCAGGCGCGACT TGCCGAGGCCAGGCGCGCCCACCACCACCACCGCGTTCGCGGAGGGCTCGTCGACGCAATGGC GCCACTCGGTCGCGAGCTGCGAGAGCTCGCGCTCCCGCCCCACGCAGGGCGTCGGCTTGCCGA GGAGCCGTGGGACGGCATCCGGCTCCTCCTTCGGGCCGCGAAGCCAGCACCCTCCGGGCCCCT WO 00/22139 PCT/US99/23535 46 GTACCGTCTCGAAGCGGCTCGCGAGCAGGCTGGCCGTCGCGTCGTCGAGCCGGATCTCCGGCG GCGACAGGCCATCTCGCCCGGCGATGAGCTGCGCGACCCGATCGACCAGCTCGCCGACCGGCA GCCTCGCCTCGACCTCGGCCAGCCCTGTCGCGACGGACACGGGCACGCCTCCGAGCGCCGCCC GCAGCGCGAGGGCGCAGTGGGCCGCCCGTGTGGCGAGATCCGTGGGCGACTCGGCGCCGGACA GCGCGACGAGCCACCAGCGCGCTTGCAGCCGATCGAGGCGCCCGCCGTGGCGCGCCGCGATGT CCCGCAGCGCCTCGGCCCGCGCGGCGCCGTCGTCCTCCGAGAGCGTGGCGCCGGCCTCGGCGC CGCCGTCTTCGGCCAGGATGACGCACATCACCTTGCGCTCGGCCGTCGTGATCGCCTCGCCCG GCGCGGCCGGCGCCGCGACCGCGCTCGCCCCGATCGAGAGCCCCTCGCCGGCCACGGCGGCGA GCTCCGCCGCGGCGGCGGCGCCGTCGCGCGGCCGCTCTCCCGCGTTCTTCGCCAGCATCCGCG CCACCAGGCGCTCGAGCGGCTCCGGGATACCGTCGCGGAGCTCCCCGAGCCGCGGCGGCTCTT CCAGGACGACCCGCATCAGGAGCGCGAGCGCGCTGTTGCCGAGGAACGGCGGGCGCCCCGCGA GGCACTGGAACAGCACGCACCCGAGCGCGAACACGTCGGCCCGGGCGTCGACCGGCGCGTCGC CGCGCACCTGCTCGc3GCGCTATGTACCCGGGCGTGCCGAGCACGGCCCCGGGCGACGTGAGGG TCGGCGCGAGCCGGAGGTGGCGCGCGATGCCGAAGTCGAGCAGCGTGACGCGCTCGACCGCGC CGCCCACGAGCATCAGGTTGCTCGGCTTGAGGTCGCGGTGAJCGACGCCGAGCCAGTGGATCG CGCCGAGCGTCGTGGCCACGCGCGCGGCCAGCGCCACGCTCTCGGCCAGCGTGAGCGGCGCCC CGGCGAGCCGCTCCTCCAGGGTCACGCCGTCGAGCCACTCCATGGCCAGGTACGGCCGCCCTG CGCCGGTCACCCCGTGCGCCACGTAC-TGCACCACGCCGGGCAGCCGGAGCGTCACGAGCGCCT CCGCCTCCCGCGCGAACCGGCGCAGGTCGTTGGCGCTCGCGCCCTGCAAGACCTTGAGCGCGA CCGCCTGCCCGGACACCCGGTCGCGCGCCCGGTACACGTCCCCCATCCCGCCGGAGACGGCGA GCCGCTCGATCTCGAAACGATCCTCGATCACATCCGCTGCGCGCATGGCGGTGCCAATGTACT CCGCGCGAGCCTCGGGCCCCCGCGCGTAAGTGCGGCCCTGCGCCCGGTTGAACGCCAGCCCGA GCGTGACCGCCTCGCGCTCGGGATCCACGGCCGCCGGATCGGTCCACGCCTCGACGAGCGCCT GCGTTGAACAACCCGCCACCGGGCGCACGCAGCCGGCATCGCCGCGCTGGCCACCCGGCGCTG CCGCCCTTAGGCTCACCTCCGCGATGCCCCGCTGG- TTCACACGGCAGGTCCCTGCAACCCGG CCGATCACTACATGCTCCCGGCCGAGGAGCGCTTGCCCGCAGTGCGCGATCTGGTCGATCGCA AGGCCTACTTCGTCCTGCACGCCCCGCGGCAGATCGGCAAGACGACCTCGCTGCGCACGCTCG CCCAGGATCTCACGGCCGAAGGGCG--CTACGTGGCCGTCCTCGTCTCGGCGGAGGTCGGCGCCC CCTTCTCTGACGATCCCGGCGCGGCCGAGCTCGCGATGCTCGCAGAATGGCGCGGCACCGCCG GCGCGCAGCTCCCCGCCGATCTGCGGCC-GCCACCGTTCCCCGATGC -GCCCGCCGGTCAGCGCA WO 00/22139 PCTIUS99/23535 47 TCGGGGCCGCCCTGCGCGCCTGGGC-TCAGGCCGCGCCGCGCCCGCTCGTCGTCTTCCTCGACG AGGCCGACGCCCTGCGCGACGCGACGCTCGTCTCCCTATTGCGCCAGATCCGCAGCGGCTATC CCGACCGCCCGCGTGACTTCCCGCACGCGCTCGCCCTCGTCGGCCTGCGCGACGTGCGCGACT ACAGGTCGCGTCGGTCGACAGCGGCAGGCTCGGGACGTCGAGCCCCTTCACATCAAGGTCG AGTCGCTCACGCTGCGCAACTTCAC-CCGCGACGAGGTCGCAACACTCTACGCTCAGCACACGG CCGAGACCGGTCAGGTCTTCCGGCC-GGACGCCGTGGACCGCGCCTTCGAGCTCACCCAGGGCC AGCCGTGGCTCGCCAACGCGCTCGCi CCGCCAGCTCGTCGAGGTCCTCGTCAAGGACCGCGCGC AAC -TAGCGGAGCACCCCAGATCCTGGGCGAAA ACCTCGACAGCCTGGTGGATCGGCTG-'CGCGAGCCGCGCATCCGCGCGGTGATCGAGCCGATGC TCGCCGGCACCGCGTTGCCGAGCGT GCCCCCCGACGACCTTCGTTTCGCGATCGACCTCGGCC TCGTGCGCATGACCGCGGAGGGCG' -2CCTCGACGTCGCCAACCCCATCTACCGCGAGATCATCG TCCGCGAGCTCGCGTTCCCGATCCGl-CGCCTCACTCCCCCAGATCAAGGCCACGTGGCTCACGC AGGACGGCCGCCTCGACGCGGACCGCCTGCTCGACGCCTTCCTCTCCTTCTGGCGCCAGCACG GCGAGCCGCTCCTCGGCGCCGCGCC CTACCATGAGATCGCCCCGCACCTCGTGGTGATGGCCT TCCTCCACCGCGTGGTGAACGGCGG-TGGCACCGTCGAGCGCGAGTACCCCATCGGCCGGGGCA GGATGGATCTCTGCGTTCGTTACGC GGGCGAGACGCTCGCGATCGAGCTCAAGGTCTGGCGAG ACGGCCGCCCCGATCCCGTCGCCGAGGGGCTCGCCCAGCTCGACGAGTACCTGGCCGGCCTGG GCCTCGATCGCGGATGGCTCATCCT-CTTCGACCAGCGCTCCGGACAGCCCCCCATCGCCGAGC GCACGCGCCGCGAGCGCGCGCTCTCC -CCCGCCGGCCGCGAGGTCGCCGTCATTCGCGCCTGAG GGAG\CTCGCCGCGCGGCGAGCGCCC -- TCCACGAGGGCCGGGCCACCTCGGACAGCGTCTCTACT CCTCCGAGGCCGCCGCGCCCCCC- C CCGGCCGCCGCCGCCGCCGCCGGCTCCAGCTCGCAGC GCACCACCAGGACCTCGCCATCCGC--GAGCTCCGGCCGCTCCACGAGCGCGTGCGCGCCCGCGC GCACCGCCGTGAGCACGTCTCCCAG-CGCCGGCTTCAGCCGCGCCAGCGTCGCGGCGTTCGCCC CGAGCGCGAGGTCGGTCACGACGCG CCCCACGCTCGCGCCGAGCTCGCTCTTGCGCTTGTTGA CCGCCGCCATCGCCGCCGCCGCCAGATCCAGGAGCCCCGGATCCGAAGGCGCCGCGACCGCCG CGAAATCCGCCGCTGAAGGCCACTT-CGCCCGGTGGATCGAGGTATCGCCCGTCTCCTCCGCGT ACACCCAGCGCCAGACCTCGTCGC

7-GATGTACGGCAGGACCGGCGCGAACAGCCGCAGCAGCA CCGACAGCCCGAGCCG-CAGCGCC'-CC-ACCGCCGAGCCGCGCGCCGCCTCCCCGGCGCCGCCCT CGCCGCGCGCCCGCGCCTTCGCGAGTCCAGGTAGGCGTCGGTGACCAGCGCCAGAGAT CCTCG''GTCCGCTCGAGCGCCGCCGCGAACTCGTGCTCGTCGAACGAGCGC -GTCGCGTCGTCCA WO 00/22139 PCT/US99/23535 48 CCACGCCCGACAGCTTGTGCAAGAGCGCCCGGTCGAGCTCCTCGGAGATCGGGTGGACCTCCG CCGACTGGCTGAGCACGTACTTGCTCGCGTTCCAGATCTTCGTGACGAGCCGCTTGCCGATCT TCAGCACCTTCTCGTCGAACGCCGTGTCCGTGCCGAGCCGCGCGCTCGCCGACCAGTAGCGGA CCGCGTCCGAAGAATACGTGTCGAGCAGGTGCATCGGCGTGACGACGTTGCCCTTGCTCTTCG ACATCTTCTTGCGATCCGGATCGAGGATCCACCCGGAGATCGCGACGTGGTGCCACGGGACCG ACGACTCGTGCAGCATCGCCTTCGCGATCGTGTAGAACGCCCACGTCCTGATGATGTCGTGGG CCTGCGGCCGCAGATCGGCCGGGAAGAGCCGCGCGTGGCGCGCCGGATCGTCCCCCCAGTGAG AGCTGATCTGCGGCGTGAGCGAGCTCGTGAACCACGTGTCGAGACGTCGGACTCGGCGGTGA AGCCG'CCGGGCTGGTCCCGCTGCGACGCCTCGTACCCGGGCGGCACGTCGACCGTCGGGTCGA CCGGGjAGCATCTCGCGCGTCGCGAGCAGCGGCCGGCTGTGATCCGGGTTGCCCTCGGCGTCGA GCGGATACCAGACCGGGAACTGCACGCCGAAATACCGCTGGCGGCTGATGCACCAGTCACCCT GGAGCCCCTCGGTCCAGTTGCGGTACCGGAGGCGCATGAAATCCGGGTGCCACTTGATCTTGT CGCCG-TATTCGAGGAGCTCGGCCTTCTTGTCGGCGAGCCGGACGAACCACTGCCGCGTGGGCA CGAAC-TCGAGCGGCTGGTCGCCCCGCTCGTAGJAACTTCACCGCGCGCTCGATCGGCCTCGGCT CGCCCCGCAGCGCCGGCCCCCGGCCGGGCGCCGCCGCGTGCTCCTCGCGGCGGAGCAGCTCGA CCACCGCCGCGCGCGCCTGCTTCACCCCCCTGCCCTGGAGCGGCGCATACGCGGCGTTGGCCG CGGCC GGGTCGCGGCTCTCCCACGCGCCCTCGCCGAACGTCACCGGCAGGACACGGCCGTTCT TGCCG,-AGCATCTGCCGGAGCGGGAGCTTCTGCTCCCGCCACCAGATCACGTCGGTCGCGTCGC CGAAGGTACAGACCATCAGGATGCCCGTGCCCTTCTCGCGATCCACGAGCGGGCTCGGGAAGA TCGGC7-ACCGGCGCGCGGAAGATCGGGGTGAGCGCCGTCTTGCCGAAGAGGTGCTGATACCGCG GGTCC\-TCCGGGTGCGCCGTGACGCCGACGCAGGCCGCGAGCAGCTCCGGGCGCGTCGTGGCGA TGACGAGCTCCTCGGCCGTCCCCTCCACCGCGACGCGATGTCGTGGAACGCGCCCGATTGCG GGCGATCCTCGACCTCCGCCTGGGCGACCGCGGTCTGGIAAATCGACGTCCCACATCGTCGGCG CGAAGACCGAGTAGAGGTGGCCCTTCTCGTGGAGATCCAGGAACGACAGCTGCGCCGTCCTGC GGCAGaTGATCATCGATGGTGGCGTACTCGTTCCGCCAGTCGACCGAGAGGCCCACCCGGCGGA AGAC-GCCTTGAAGACCTGCTCGTCCTCGCGCGTGACCTTGTGGCAGAGCTCGATGAAGTTGG GCC- 5 C GACACGATGCGCGGCGGCTCCTTCTTGATCGTCTCCGGCGCGGCCTGCGGCAAGGTCA GGC C 3 CGCTCGTACGGCGTGCGCACGTCGGTGCGGACGTGGAAGTAGTTCTGCACGCGCCGCT CGGG-GGCAGGCCGTTGTCGTCCCAGCCCATCGGGTAGAAGATGTTGAAGCCGCGCATCCGGC GCTGG-2CGGACGAC GACGTCCGTGTGC-GTGTAGCTGAAGACGTGGCCGATGTGCAGCGAGCCCG WO 00/22139 PCTIUS99/23535 49 AGGCGGTCGGCGGCGGGGTGTCGACGACGAAGGTCTCCTCGCGGGGGCGCGACGGGTCGTATC GGTACGTCCCGTCGGCCTCCCACAGGTCGGCCAGGCGCAGCTCGGCGACGGGCGAGTCGAAGT GCTTCGGGAGCGTCGCGGGATCGATGGAGCGGAACGTCTTCTTGATCGTCACGTGGTCACCTG CAGAACAGACCCCGCAGGAACCGCCCGCGGGGCCGGCATCCTACGTCGTCCCCCGGGTGCCGC TCAAGGCGCGCCGCGCCCGCGCGGCGGCGATCCGCGATCGCATCCGCGCATCCGCCAGAGCCC GGCGGCTCCGCCGGCGCGCGCGCGCCGTCCGTGGAGCCGAGAGGAGAGGCCGGCGCCCAGGTC GTGGAGGACGCCGGCGGCGCCGCCGCGGAGATCGCGGAGAGGCGGGCGCATCGATCGCGGCGA GGCCGGGGGCTCAGTCGTAGCGCTCGACGTGGACGTGCTTGCGGTGGACGCCGAGCTCGCCGC GGGCGAGCTCGCGGACGGACGAGACCATCCGATCCAGGCCGCAGATGAAGACGTGCGGCGCCG GATCTCCGCTCTTCTCCGCGAGCTCCCGGTAGAGCTCGGGCACGTGCGCCTGCACGTAGCCGC GGCGGCCGGCCCACGACGGGCCGCCGCGCGAGAGCGTGATCTCGTAGCGGATCCGGTCGGATC CGCGCGCGAGCGCCTCGAGCTCGTCGCGGTAGATGACGTCCTCCTCGAAGCGCGCGCCGAACA GGATCCACAGGTGGGGCGCGGCCAGCCCCGCGCGCAGGGAGGCGCGCAGCATGCTCCGGAGCG GCGTGATGCCGGTGCCGGTCGCGACGAACAAGGAGGGCGCGGAATCCCCGGGATCGCGGGTGA AGAGCCCGTGCGGGCCGATGGCGCGGAGCGTGGCGCCGGGCTCGAGCCGGTGCAGGTGCTCCG AGCCCGCCCCGCCCTGCACGAGCGTGACCGCGAGATCGAAGCGGGGCGAGCCGTCGGGCGCGG ATGCGATGGAGTAGGCGCGCTTCACCTCGCCGCCCGGGAGCGGGAGGACGAGGTTGACCCACT GGCCCGCCTCGAACAGAAACGACCTCCCGTCGGCGCGCTCGAACGAGAGCTCGCGCACGAAAG GGCTGAGGGGCCGGGCGGCGACGAGGCGGGCTTCGAACGGTTCGGCGTGGATCATGGTCGGGG CCCGGCGGGGCTCGGCTGCGAGGCCGCGCGGGTGGCGAGGTCTTACCGCAGCCTGCGCCCCGG CCCAATCGCGATCGCCGCGGGAAGGGCGCCGCCGGAGGGCGCGCAATCGCGGGAATCACGGGC TTCCGCCCCGTGCGCCGCCGGAGCGCGCGGCCGGGCCGCCGGCCCGCGCTCCGGCGGGGAGCC GTCGCGGGCTCTACCGCACGCCCATGCGGCGGCGCTGCGGGATGTTCACCGCCGGCCGGGAGC GATCCTGGTTGGGGAGCGCGCGCGGCGGGCGGGGATCCCGGTGCGCGGGCTTCTGCGCGGGGA GCTGCCCTCGCTGAGCCGGGCGCTGGTCGGGCGACTTGGCCGAGCCCAGCGCGAGATCGGAGA CGGGGAGATGCGCGCGTCGCTGCATAGAATCCTCCATGGAATCGGTCATCAACACATCGGGAA GAGCACCCAGGCTGAAAGAAACCTTCGAAGAACCGGCTCTCATACACCCTCCATTCATCGTGC GACCCCGGATTCAGGACGGATCGAACCCGCGAGGGACGCTGGCTCTCTGGGCCTCTCCCTGCT CGC TCGACCGGCGCCCTCTCGACGCAACTCCGCCGTTCGTCGGGACGGGACGGTCCGCCTCGC CGCACGCTCCCCGTCGAGACGACTCAGCGTCTCGACGTCAGGAGAGATGACGACTCGGCCCGT WO 00/22139 PCT/US99/23535 50 CGCGCCACGACCCTTCCGGCTCGGTSCTTCGAGCGCGCGGCCAGCGAGCGAGGGGCGATCGCC AGGAGATCACGAATCTCCCGGCCATC-GGCCTCCAGCGCCTCGGGCTCGTTCGCTCGTCGCCCC GCTCCGTCCCCGCGCGCGCACGACGC GAGCTCGCGCGGGGAACCGCGGGCCGCTGTCGTGGCT GCTGATGCGCGACGATACAGGGGGGACGCCGTGCCTACCTGGGCAJACAGGCGCTCATCTTCTA DCCACGGCGAGCACTACGGTGAGTGCTGCCATGAGTAGGCCCCTGAGGGTCCGCGCGACGGAGC GTGGTGTCAGCGAGAGATGCGCATCG-:TGGACGCGGGCTACGCGTCGAGAGGGACACTAGCACT CGACCTCGATCCTGCCCAGCACTTTTTGTCGGGGAGGGCTGCCCTCCCGCTGGCCGCTGGCCG CTGGCCGCTCGCCGCTGGCCGCTCCC-CGCTGGCCGCTGGCCGCTCGCCGCTGGCCGCTGGCCA TGTGCGACGTGAGCTCGAGCAGCCCG CGGCTGACGGACAGACCCCGGAGTTCATCGAGCCGGT DGATGCCGAACCCGCCAAGCGAAAAA-ACGTATCCGTTCGGCAGGTCGTGGCCTATCATGCAAGC TGCTCGATGCGCTGACAGGCTTCT--CGAGATCCTCGTCGGTCTTTGCGAGCAACCGCATG AAGCGACTCCCCTGCGTCCCTTCQAzAAGGCGTCGCCTGGCACGCCCGCCACCCCGGTCTCG TCGAGCAAGTAGATGGCTCGCTCTCG-ACCTGTCCTCCCGGGTAGGCGAGACACATCCGCCAGC ACGTAGTACGTCCCCTGCGGCACGCAG1-GGTGGCAAGCCCGCTTTCTCCAGCGCCCGACAGAAC CGGTCTCGCTTCCGTTCATATCCCT-GGGCAAGCCCCGTGTAACGAGCGAGGJAGGCCGCGG ATCCCGGCAGCGACTCCATGCTGCAGCGGCGTCGGCGCGCAGACATACAGCAGGTCGCTCATG GCTCCAATGGCCTTCGCCCACCTGGCj ATCGGCCACGCTGTAGCCGATCCGCCATCCTGTGATG CTGAAGGTCTTCGAGTAGCCGCCTAT-CGTGATCGTACGCTCGGACATGCGCGGAAGGGAGGCG ACGCTGACGTGCTCACGGCCGTCGAGATAGTACTCGTAATTTCGTCCGTGATCACCATG AGGTCATGGTGGCAGGCGAGATCGGC2GATCTGTJTCCAGCTCCATTCGGCCGAACACCTTCCCG GAAGGATTTCCAGGAGAGTTCACCACGATCGCCTTGGTCTTCGGGGTGATCGCGCGCTCCAGC TCGTCGCCGTCGACATTCCAGCTCAG 'GGATCGCGCCGTCACATACCGCGGAACAGCCTCGACG GCGAGGATAGCCTGGGCGTGATAGGC -ATAAACGGCTCGAAGAGCAGCACTTCGTCCCCAGGA TTGAGCAGGCCATGCAAGTGGCCTLGAAAGGCCCCTGTCGCTCCGGCGCTCACCGTGATGTCA *GTCTCCGGATCCGCCGCGATGCCATT ATGGCGAGCCAGCTTCGCCGCGATCGCATGGCGCAGC TCCACGATGCCGTCGAAGCGCGAA7TATGTATTGCACCCCCGATCCATCGCCTCCTTCACCGCT TGAAGGATCACCGAAGGAACTGGGGT7-ATCACAGACGCCCTGGGACATATTGATCCCATGGACC TTGGCGCACGCCAGGGTCATGGTAC IG -- ATATCG"'GACTGGGCGAGGCGAGCCGCACGATCACTC GGTAGACTCTTCATCAGCGTGCTCZ--GCTTCTGTTCTGCGG--CTCTGCATGGTGTCTTCGGGTG GGCTTGTCAGCTCGACGCGCCCATGC -AGCGGCGCAGCCCTAGCGGCCGCAGGTCTGTCCACAC WO 00/22139 PCT/US99/23535 51 TTCTTTGATGAAAGCGAGACATT -CCTTTCGTGCCCTGTTTGCCCGCAGCCCTCCAGCCCCC AGGTACGGGCTTGTCGGCGGGCCAGATCGAGTACTGCTCTTCGCCGTTCACCACGACCTGGCA ACGCG-TCTTGCTTTCGTCGTCCCGAT TCATGATTTTCCTCGCCCTTCGTCAGCGCTGCGCGAG CATGAAACGAATCGCTCATCGGCGC ACAGGCGCGCGCCGGCTGCCCGGAGGCACTCCCACGCC TCCCTCACGGCAACCTCATCGCTCCG,-GATGTTCCCGATGGCGACTCGGATCGTGTACCTGCCG TGGAGACGGGTATGGGACAAAAATAC CCTGCCCGACTTGTTGACCTCGTCCAGCAGCGCCTCG TTGAG--GCGATCGAGCTCGCGTTCGA -CGACT.CTCTCTCTGCCTCGTCCGCCGACCGCATGATG CAAGC-GAGCGCGGAGGGCCTCATG C-AAAGCAGACCGTACTGAACGGCGTCGGCGCGAGGCGC TCCCAATCGGGATCOGCGTCCACC CACr-TGGGCCAGCTGCTGCCCCAATCGGAGGTGCTCCCGG ATCCG GGCCGCCAGCCCTTCATGCC--GAGTACGCACGATCATCCAGAGCTTCAGCGCTCGG AAGCG'" CCGACCGAGCTGGATACCC CAGr'TCCATGTAATTCGTGACGTCGCC CTCGGTGCGGAGG TATTCGGGCACCAGACTGAACGC C CGCTTCAGTCGGTCGGCGTCACGCACGTAGAGCACGCTG CAATCCATGGGGGTGAACAGCCAC--TLGTGAGGGTTCACTACCAGCGAGTCCGCCCCCTCGCAG CCCGCGAGCACGTCCCTGTGCTCG3-:GGACGATCGCGGCCATCCCCGCGTAGGCCGCGTCCACG TGAAGCCATAGCCCGTGCTCCCGGC-r-AACGCTGACGATGGCGGGGATGGGGTCGACGCTCGTC GTGGACGTCGTGCCCACCGTCGCCCCu -GACGCAGAAGGGTCGGAGGCCGGCCCCGAGGTCCTCC ACGACGGCGGCGCGCAGCGCCTCGGG3,-GACCATGCGGAAGGCCGGATCCGTGGGGATCTTCCGC ACCCC -CTCCTGCCCGATGCCGAGG- rn-GATGGCTGCCTTCTCGATGGATGAGTGCGCCTGCTCC GACGC7GTAGAGTCGCATGCGCCGCTG-,-TCCCGCCATGCCCCGGAGCCGGATGGTCGGCTCGGCC GAGT-CGCGCGCGGCCGCGATCGCC:C--CATGCTGGCGGTCGACGCGGTGTCCATGATCGCGCCG TGCAAGCCGGCGTCGAGATCCAGC'-m-CTGACGCAGCCAGGAGAGGACGAGCTCCTCGAGCTCG GTGGCCGCCGGCGACGTGCGCCA-TAGCATCACGTTGACGTTGAGGCACGCCGCGAGCAGCTCG CCGAGGATCCCAGGACCAGACGCC3 :TGTTCGCGATACGCGAAGATCGCGGATGATTCCAG TGCGTGATCCCCGGCAGAATGATC G-'CTCGAAATCGGTGAGCACGGCGTCCATCGGCTCCGGC TCGAC-GGGCGGGCTCGGGGCCAGC -CTGCCCTTCACGTCGCCGGGGCGGATCGCGGGAAAGACG GGGTATCGATCCGGGTGCCAG-ATCGGCCGCCCATCGATGATTCTCATACCGATCCGG CGGAACTCCTCCAGATCCATGTCC CC -GAGCCGTTCTTTCCGCGGGTCGCTCACGTCAACCTCC TCG-CCTGCCAGGACAGGATCCTC3 -AGGTCCCCTGGCTCCGGCGGTGGAAGCGCTCCTTGAA CGTGA-zAGGCCCACGGGGTCGGTCCQ-TAGCGCCGCAGGTGCTCGAGCCGATCCTGCCCCTCGCG GAC 2 - 3 ACGGGATGTGCCCGGCCGQG---A CCCACCACAGCACGAGGTAATGCGGCTCGAGATGCTC WO 00/22139 PCT/US99/23535 52 GAACCACCGAGCGCGCTGTCGCAGGAACGCGGCATGATCCGCGGTGTAGGTGAAGGCGAACAG GTGCTCGATGGAGGTCCATACCGACAGGGTCACGAGGAGCCGCTGGTCCGGGTACGGACGGAT GGACACAGAGTTCCCCTCGGCCGTCTGCAGGCGCCACACGAACCCCTCGCTCCGATCGGCCAG ATGGTTGATATGGTCGAGCCCCTGGACGAAGCCCTCCATGATCGGATCCTCCAGCGGAGCGCG AATACATGCGAAGTTGTATTGCGCGATGTGGTGCCGATGCTCCGACATGTCGCTTTCCATCTC CAGCTCCCGCTCACCAATCCCAGCGCTGCTCCGGGGAGCTCATCAGGGCAGACGCGACATCGA TCCCGAAGCTCCGCCGCATCCCCTCGACGAAGGCGGCCTGGACCGCTTCGGCGACGGATCGGC CTGCCTCCGGCAAGACCTCGGAGACAAAGAAGAACCGCCTCGTGGAAGGGACAATCTTGCCCC GCTCCGCCTGGCGCCATACGAAGTGCCTCGTCACCAGTCCCTCCGCGTCGGCATACCCGACCT CGCCGGCGCCGACCGCCACGCTGCCGCCTGAGCCGAGCTCCACGAACGCCTCACCGCCTCGCG AGATCTCGAGGCGAACGTCCGGGCCAGCCAGATCGCCGAGGTCCCAAGCGCCGACGGGGACGG CGAACCGCAGCGACAGGAGGTTGTAAAAATCGACGAATGCGTTGATGTGCGGCAGCTCTCCAC CACCGAGGACCCGCTTCGCCAGCGCCTCGATCGAGCTCGGAAATTTCTTGCCAGAGACCCCCA CTCGCTTCATCGCCTCGCGCCAGGCAGCCACGTGCGGATGCGACTGGGCGTTTTCGTGGCCCC AGCTCCGTCGCAGCTCCTCCTCGACCTTCCGGAGCTCCTCCAGCACGGCCGGCCGCTCTGCGG CGTTGTCCAGGCCTTCCCCGTACCCGGTGACCAAGATCATCCCAGGAAACGACTCCCAGATTC GCGGATCGACGATGAATGCCATGTGCCTCCTGCCCCTCGAGAGCGATCGCCTCGATCGACACC AGGCTGTGGATGCATGAGCCGGGCCGTGCGGACGCAGGACCCCGCTACTCATGGCTCTTCGTG GCCGATGAACAGGTCCTCCACCCGTCGATCGTGCTCGGTGCCCCGATCCGTCCAGTCCCACCC GCCGGCGACCGCGATGTTTGCACCCGAGACGTACGAGGCGCGGTCGGAGGCGAGGAACGCCAC AGCATCTGCGACCTCGCTGGCGCGCCCCAGGCGGCCCATGGGGACGCGCCGCTCCATCCACTC CTTCTGCGCGGGCGGAAGGTATCCGTTGTCGATGAGCCCTGGAGACACACAGTTGACCAGGAT TCCATGAGGCGCCTCCTCCGTGGCCAGGCTGCGCGTGAGGATGAGCACGCCGGTCTTCGCGAT CGAGTACGCCGCCACGTTCGGCGCGCCGCGGATCGCGTACGTGGGGCTCAACCCGATATTGAT GATCCGGCCGCTCTTTCGCTGGCGCATGCGCGCCACGGCCGCGCGACAGAGGTAATGAACGCT GCTCAGGTTGCTGTCCATGACGTTGCGCCATTCGTCGTCGGTCATCGCCGCAAGCGGCTTGAA GAAGAAGTCGCCCACGTTATTGACGAGGATGTCGATGGGGCCCAGCTGCGCCTCGACGCTGGA GAAGAGCTCCGCGGCCGCGTTGGGGCGGGTGACGTCGGCCTGCACCACCATGGTTCGTCGCCC GAGCGCGCGGATCTCGGCCGCCGTCTGCTCGGCCGCATCCTTGTTCGAATGGTAATTGACGGC GACGTCCGCGCCTTGCTCCGCGAGGCGCAGCGCGATCGCCTTGCCAATTCCGCGCGAGCTACC WO 00/22139 PCT/US99/23535 53 GGTGACCAGGGCGACGCGCCCGGCGAGCTCCAGCGATCGCGCCTGTGGCAGGGCCGGAGCAGC CTCCTGGTGGAGCTCGACGTCGACGGGGAGCTCCACGTGGTAGCTCGTCTCTCGCGGAGCCGC GCAGTACCTCTCGTAGAACGCCTCGAGGACGGGCTCTTCGCGTCGCATGATGTCCGCGTGGGA TTCGGCGCTGCGCCACGGATAGAGCACCAGGATCTCGTCGGGGCGCACGGTGCTCTGAAAGAA 5 TCGCGCATGACCGCACCACCCCGGGTGTTCGTGGGCTCCTGGGCCGAGCAGATCATCCATTTT TTGCATGATCTGCGTGGCCTCGCCCTCCATGCCGGGTTTGATGCGCCATCGCTCCATAACGAG GATCATGTCTTGGCTCCTGTTCGTCATCGCCGTTTCGATCTGGGGGGGCTGCCCGCGCTCTCG AGGGCGCGCCCCTTGTATTGGCCGCGGATGGTCTGGGTAGCGCTCGCGAGCTTTCGCTTGTGG GCGGCGTTCAGGCTTGCGCCTTGATTGACGAACCGCTCGCAGACGAATGCGTGCGATTCATAT D GCGGTCGCGAGCGCCCACAGGTAGAGACGGTGGCTACGAGCGAGCTTGGGCGGAAGCGCCCTC AAGGCGGGTCGGATGGATTTGAGGGTGCGAATCAAGCGGGCGTGCTCTTCGAAGAAGAGACCG CTGAATCCATCCTGGACGAACGGCGGGGCCATGGTAGGTCGCACGATGTTGTTGTAATCATCA TTCGAGAAATCGCCGGTAAACCGGAAAGATGCCGCCGTTGCCCACCAGAGCTGCGTGGAGATC GCGAGCGCCTCTCGCGCCCTCGGAACGTCACGGTTGGCGAGCGCCTCCGACAGCCACCTGTGC D GCCATGAGCAGCGCCTGGACCAGCACGAAGAACGCGTGATGCCCCAATACCCAGCGGCCCAGC GCGCCGTCCGGAGCGCCCGCCTCCGCCGGAGGCGCAGCCAGCTGCGGGATGCCATTCCATGAT TTTGGCCTTCGCTTGCCGGAGAACTGGTGGAGGATGTCCTCGATGGACGCACAGAGATGCCCC ATTTCCATGGGTTGCAGGGAAGTACCTTTCAGGCTTTCGCGGATCATTCGGTAATATGCGACG ATCACCGCTTCGCAGTACGTCTCGAGCGGGTCTGGGGCGGAGACCCGGTGCACATGGAAATAG GCGTCGTACTCCGCCTCCCGGTCCGACAGGCTCCCCGGGATGTCCGGATCTGCCGCTTGCGCC TGCCATCGCTCGAGGATGGGGACGGCGAGGGGGGCGAGATGCTCGGCGAGCACCGCCAGGTCG CCCTCCGGCGCATGCGCCAACAAGACCTCGAAGGCCTCGGCTGCGACCTTGGAGGTCTCGCCC ATTCCGACGGCCTCGATGGCTTGGGGCAGCGGTAGATGGATGGTATATTTAGCCATGATTTGC CCGAAGATTGCCGCTGCGTCGACAGATCTTTCGCGAGCCGGAACGCCATTTCCACTGCTCTGG CTCTCAATATTGAATTGAGCCCTGGCGACTGCCATAGGCCCAGTCGCTCGACACAGTGTACGG AGCGGCCCGATGCTTTCTCCTTTTTTAGTCCTGCACCGAATACTTCTGTTGGGCGCCAAAGAT CCCTTGCCGAGACTGTCCGGCGAGATGTCGTGTGCGAAGCGTCCGCACGTCCAGCGGGCCCAT GCGTTGCTAGAGCATAAAACGGTTCGATGCCTGGTCGAGAGGGAGACGCGAGGAGCCTCCCTT TGGGACGGATGAGGAATTTCGTGACCGAAATGTCGGCAGGAACAGCGGCGCAGAAGCGGCGCA TCGATGGGGAACCATGGGTTACGAAGACATTGATGATAATGTCGACGCAATCGCAATCGTCGC WO 00/22139 PCT/US99/23535 54 GATAGGGCGTTCCCGCC/' '.""--'AAAC GTCGAGGAGCTGTGGCAGAAGCTCCGCGCTGG CGTGGAATGCGTCGTCACCTTCACAO-AGGCCGAGGCGCTCGCCGCGGGGGTGAGCCGCGAGAT GCTCGCGAATCCCAGCTACGTGCGC-AGAGGCGCGCCGCTCGACGGCGTGGAGCTCTTCGACGC CTCGTTCTTCGGGTTCAGCCCGAGI c'-AGGCAGAGAGCATGGATCCGCAGCAGCGCATCTTCCT GGAGGTCGCCTGGGAGGCCCTCGAG'CGCGCCGGTTACGACCCCGATGCCCATTCCGGGCCTAT CGGCGTCTTCGCGGGCAGCGCCCCGAGCGGCTACCACTCCCTGGCGCAGTCCGACCCGGAGAT CCTAGGCGCCCTCGGCCACTACC-CTGACGCTGAJCA1&CGACAAGGATTATCTCACCACACA CGCCTCGTACAAGCTCAATCTGCGGG GCCCGAGCGTGTGCGTGCAGACGTCCTGCTCGACCTC GCTCGTGGCCGTGGTCATGGCCTGC -- AGAGCCTGCTCAACCACGAGTGCGACATGGCGCTCGC GGGTGGCGTGGGGATCCATGCGCAT-CAGCGGAGGGGCTATCTGTATCAGGAGAACGGCATCTC TTCGCCCGATGGGCATTGCCGCGC T-TCGATGTGGCCGCCAAGGGCACCGTGGGCGGCAGTGG CATAGGCATCGTCGTCCTGAAGCGr-TCGCCGACGCGCTCGCCGACGGCGACCACGTGCACGC GGGTCAGGGCACAACAGCCACAACGTCCGGCA CGTGCAGGGGCAGGCCGAGGTGATCCGCATGGCCCAGGCGCTCGCCGGCGTGGAGCCGGATGA CATCAGCTACATCGAGGCGCACGGCACGGGGACGCCGCTCGGCGATCCCATCGAGATCGCAGC CCTCACGCGCGTGTTCCGGGCGAAGACCGCACGAAGGCAGTTCTGCGCCATCGGCTCGCTCAA GACCAACCTCGGCCACCTCGATGCCSCCGCGGGCGTCGCCTCGCTGATCAJAJACGGTCATGGC CCTCGAGCACCGCGAGCTGCCCCCGAG'"CCTGCACTTCGAGCGTCCGAATCCGAAGCTCGAGCT GGAGAGCAGCCCTTTCTACGTCAACACCCGCCTCACTCCGTGGCACGCGGCACGAGGTCCGCG CCGCGCTGGCGTCAGCTCGTTCGG2A -TCGGCGGCACCACGCGCACGTGGTCCTCGAGAGC TCCGGCCCCGCCTCCGAGCGGCCC : CGbGCGTTGGCAGCTCCTCACCCTCGCGGCTCGCTC CGGCGGTGGGGCC z- -GAAGTGGACCACCATCGA ATCGATCGCCGATGTCACGTACACGAG-CCACGTGGGGCGCCGGGCCTGGCCCTTCCGGCGAGC GGTCGTCGGCGAGAGCGCCGCGGATC-TCCGCGCCGCGCTCGCGAGCGAGGGCTCGCCGCGCTC GATCTCGTCATGCCAGGCGGCGAGG Z3AGAGGCCCGTCGTCTTCCTGTTCCCCGGTCAGGGAGC GCAGCACCTCTTCATGGCGCGGGAC-:CTGTACGAGGTCGAGCCGATCTTCCGGCAGTCCCTCGA CCGCTGCGCCGAGCTCCTGCGCGGC-CCGCTCGGCCTCGATCTGCGGCAGGTCCTCTACCCCGC CGAGGGGCAGCGCGACGACGCCGAG :-AGGAGCTCGGTAGGACCGCGATCGCCCAGCCCGCGCT GTTCGCCATCGAGCTCTCGCTCGCC AAGCTGTGGATGGCCTGGGGGATCGTCCCCCAGGCGAT GATCGGCCACAGCGTCGGCGAGTTC3C -CGCGGCTTGTCTGGCGGGCATCTTCCGCGAAGAGGA WO 00/22139 PCT/US99/23535 55 CGCGCTCCGCCTCGTCGCCGAGCGGGGCCGCCTGATGCA.JCAGATGCCGCCCGGCGCGATGCT GGCGGTGCCCCTCGCGGAGCCCGAGCTCGCCCCCTACCTCAGCGACGACATCTCGCTCGCGGC GATCAACGGTCCGGCTCTCTCGGTGGTCGCTGGGCCGATCGAGGCCATCGACGCGCTCGCGGC CGAGCTCTTGGACCACGGGCTCTCGTGCCGGCGACTCCACACGCGGCACGCCTTCCACTCGAA 5GATGATGGCCCCCGTCGTTGACGCCTTTACCCGATGCGTGTCCGCGGTCGAGCGCCGCCCGCC GTCAGGCCACTTCCTCTCGACCCTGACGGGCGGCTGGATCTCCCCCGAAGCAGCGACCATCCC CGCATACTGGGCCCGGCAGCTCGTGGAGCCGGTGCGCTTCGCCCAGGCCGTGAGGCAGCTGCT GTCCGAGTCGACGTGGCTCTGGCTCGAGCTGGGTCCGGGCCAGACCCTGAGCCCGCTCGTACG GCAGCAGGCCCGCGCGGATGGCGGCCAGGTGGTCGTCGCCTCGCTGCCGCGCGCGAAGGACGC DGGGCG-CCGACCACCTCGCGGTCATCGAGGCGCTCGGCCGTGTCTGGAGCGCTGGTGGGACGGT CGAC'-GGAAGCGCTTTCACGAGGGCGAGGCGCGGCGGCGGGTGCTGCTACCGACCTACCCCTT CGAGCGGCAACGATACTGGGCCTCTCCGCGCCACACGAGCGCTCCGCCGGAGCGATATCAA GCCGCTCCTCGCGAAGAACCCAAACGTCGCCGATTGGTTCTTCCTCCCTGCCTGGCGGCGCTC GGAT CCTCCGGTCTCGTTCGACGCGCAGGCGGTGACCACGCGGCGCTCTACGTGGCTCGTCTT DCATCG-GGGACGAGGGCCTCGGCGCGGCGCTGGTGGAGGGCCTCGCGCGGCGGGGGCACGAGGT CGTCGCGGTGGTCACGGGTGAGAGGTTCGAGCAGACGGGCACGCAGCGCTACACGATCGATCC CGCCG 'CGAATGGCGATGTTGCGTCCCTCTTCGCGCGGCTCGAAJJCGA]kGGGCGCATGCCGGA CCGGATCGTCCATGCCTTCTGCACGr'TCGCCTGCGGACGGCGCGCGCATCGAGCGCGGAGCCGC GCTGG7,-AGATCGAGCGCAGGCTGGGC-TTCGATAGCCTCCTCCTCCTCGCCCAGGTGATCGCCGC ACA-AGJGCATCCGAAGCCGCTGATG -CTCGGCGTGATCACGACCCGGGCGCACTCCGTCATCGG AACC-GAGATCATCGAGCCCCTGCGC -GCTCTGGTGCTCGGCCCCTGCCGCGTCATCCCGCAAGA AATACCCATGTCTCGTGCCGGAACATCGATATCGATCTCCCGGGCGAAGGCGGGCGCGCGGA GATCG- CGGCGCGCCTGATCGCCGAT7CTGGAGCGAGAGTCGCCCGACTCGGTGGTGGCCTACCG CGGCCGGCCGGCGCTGGGTCGAGAGC-ATAGAGCTCACCGATGTCGGCCGGCGGTCAGCTGGCGC CGCCC''-CGCGCCTCCGCCAGCGCGGG-GCGTACCTCATTACCGGCGGCCTGGGGGGCATCGGCCT CGTGX 3TGCAGAGCTCTTGGCCCGAGAGGCGCACGCACGGCTGATCCTGGTTGGGCGGACAGG CCT- CCAGCGCGGCAGGGGTGGGAC'GACTGGCTCGCGGCGCACGGCGCGGGCGACGCGACGAG CCCGAAGATCCTCCGGATCCGCGCCTCGAGGAGGCCGGCGCCGAGGTGAAGATCGCCGCGGC CGACG--TCTCCGATTTCAATGCGATGC-GGAGCGTCATCGAGGAGGCCCGGACGCG-CTTCGGCCG CATCH :3ACGGCGTCATTCACTCCGcCGI-GCATCCCGAGTGGAGGCATGATCCAGCTCAGGACGCC WO 00/22139 PCT/US99/23535 56 GATGGCGGCTTGGCGCGTGATGGCGCCGAAGGTCGGCGGCACGCTCGTGCTCGATGCGCTCCT CCGGGACGAGCGTCCCGACTTCCTCCTGATCTGCTCGTCGTTGGCCTCGCTGGTCGGCGGCGC CACCCAGATCGATTACTGCGCCGCCAACGCCTTCCTCGACGCCTACGCGCAGAGCCGCGAGGG CGAGGAGGGATGCCGCGTCATCTCGGTGCAATGGGACACGTGGAGTGACGTCGGGATGGCGGT GGACTTCAAGCTCCCGGCCGATCTCCAAGAGGGGCGCCGCGAGAGCCTGAAGCGGGGCATCAG CTCGAGCGAGGGCGCCGAGGTGCTCGGCCGCATCTTGAGCGCAGGCATGAGCGGCCCGCTGGC GATTTGCACGTCGGATCTACCAGCGTACAAGCAGTCTGTCACGACACGCCGATCGCAGCACGA GCAAACTCCCGCCGCCCGGCCGATGCACTCGCGCCCAACGACCACGGGAGCCTATGTCGCTCC CGAGACCGAGACCGAACGGCGCATCGCCGCGATCTGGCAGGATCTCCTCGGCCTCGAGCAGGT AGGCGCAAACGACGATTTCCTCCAGCTGGGCGGCCATTCGCTGTTGGCCACGCAGGTCCTGTC TCGCGTCCTGCAGACCCTCAAGGTGGGGATCTCGTTGCCGCAGTTCTTCGATGCGCCGACGGT CGCAGGGCTTTCGCGCCTGGTCGACGCAGCACGGGCCGAAGGCGCCGGACCCGTCGCGCCGGC AATCGGCCGTGTCGAGCGAGACGCCTACCGAATCAAGCCGCCCGCGGCCGAACAGGCCGCCCG CACCAAGCCGTAACAAGAAGGGGATCGAGTCATGGAACCCGTCGGCGGCGTGGACATGAATCA GCCCGCAAAGCAGCAGGAGACCTGCGTCTTCCCGACCTCCTTCGCGCAGCGGCGGCTCTGGTT CCTCGACCAGCTCGAGCCGGGGAGCGCCGTCTACAACATGCCCGCCTCCTTCCGGACGCGCGG GCCGTACGACGTCGACTCGCTCGTGCGCAGCGTGAACGAGATCGTGCGGCGCCACGAGTCGCT GCGCACGACCGTCGATGTCATCGATGGCGAACCCGTGCAGGTGATCGCCCCCTCGCTGCGCAT CGAGGTGCCCGTCGTGGACCTGAGCGAGATCGACGAGCCGGAGCGAGAGGCGGAGGCCCGGCG GCTCATGGCGGAGGAGAGCCGCCGCCCCTTCGATCTCACGCGAGGGCCGCTGCTCCGAGCCAA GCTGCTCCGGCTCGGCGAGGCCGATCACGTGCTGATCTTGACGATGCATCATATCGTCTCCGA CGGCTGGTCGATGGACGTGCTGTTCAAGGAGCTTTCCACGCTCTACGCCGCCTTCCACGAGGG CCGCCCGTCGCCGCTCCCGGAGCTGCCGATTCAATACGCCGACTTCGCGGTGTGGCAGCGGGA GCTGCTCCAGGGCGAAGTTCTGGAATCGCACCTCGGGTACTGGAGAGAGCACCTCCGCGGCGC CCCCACGCTGCTGGAGCTTCCGATGGACCGGCCCCGGCCGCCGGCGCAGACGTTCCGGGGCTC CCAGCGCGCGTTCCGACTCCCACTCTCCCTGCAACAGGCGGTGCAGGCGCTCAGCCGGCAGGA AGGCGCGACCCCCTTCATGACGCTGCTGACGGCGTTCAGCGTGCTGCTCTCGCGTTATGCGCG GCAGAGCGATCTGGTGGTTGGCACGCCCATCGCGAATCGCACCCGAGCAGAGCTGGAGGGGCT GATCGGCTTCTTCGTCAACATGCTGGCGCTGCGCATCGACCTCGGGGGCGACCCGAGCTTCCG CGAGCTGCTCGGGCGGGTGCGGGAGGTGACGTTGGGCGCCTACGCGCACCAGGACCTGCCCTT WO 00/22139 PCT/US99/23535 57 CGAACGGCTGGTGGAGGAGCTGTCACCAGGGCGGAGCCCCAGCCACAGCCCCTTGTTCCAGGT GTCCTTCACGTTGCAGAACACCCCGATGGATGCGACGAACAGAGCAGACATTGCATCGGGTGG CGCGCCGCTGGTGGAAATGAAGGCGGCGAAATTCGATCTGATCCTGGAGCTCTCGGAATCGCC GCAAGGGTTGCTCGGCACGTTCGAGTACAACACCGACCTGTTCGACGCCGGCACCATCGAGCG 5 GATGGCCGGCCACCTGGAGGTGCTGCTCTCCAGCGCCGTCGCGGCGCCGGATCGACCCATTGC GGAGCTGCCGCTCATGGGGGCCGAGGAGCGCAGTCGGGTATTGGTGGAGTGGAACTCCACTGC CGCGCTGTATCCCGAGGACCATTGCATGCACGAGCTGTTCGAGCAGCAAGTGGAGCGGTCGCC CGAGGCGACCGCGGTGCTCCTCCAGCAGCAGACGTTGACGTATCGAGAGCTGAACATGCGCGC CAATCAGCTCGCGCATCACCTGCGGAGCCTGGGCGTGGGCCCAGAGGTGCGCGTCGGGTTGTA D TCTCGAACGGTCAATCGAGACGGTCGTGGCGATCCTCGGCGTGCTCAAGGCTGGCGGGGCCTA CGTGCCGCTCGATCCGACGTACCCCAGCGAGCGCCTCGGGCTCATGATGGCGGACGCAGCGCC CTCGGTGCTGCTCACGCAGGCGTCGCTCCTCTCGAAGCTGCCGCCCCACGGGGATGCAACGCT GGTACAGCTCGACGCGCTGCACGAAGCGCTCTCCAGGCTGCCACACCATACCCCGCGGAGCGG CGTCACCGCCCAGAACCTCGCATACGTCATGTACACTTCCGGCTCGACCGGGCGGCCCAAGGG CGTGCTCGTCGAGCACCGCGGCCTCTGCAACCTGCCCACCGTGCAGGCCAAGCTCTATGGAAT CGCGCCGGGCGACAGGCTCCTCCAGTTCGCGCCGCTCTGCTTCGACACATCGTTCTGCGAGAT CGCGCTCGCGTTGCTCTCGGGAGCGACGCTGGTCATGGGCACGGCGGACGAGCTTCTCCCGGG ACCTCCGCTGGTCGAGCTGCTGAAGAAGCACGCGGTCACGGCGATGCTCCTGGCCCCTACCGT GCTCGCAGCGCTGCCAGAACAACAGAGCGCGGCGTTGCCGCTGCGCGTGCTCACGATGGCCGG TGAGGCGTGCCCGGCGGAGCTCGTCAAGCGCTGGAAGGCACCCGGACGGCGCCTGTTCAACTC CTATGGCCCGACCGAGACGACCATTTGGGCAAGCTCCGCAGCGGACCTGTCCGACGAACGGAT CCCGCCCATCGGCCGTCCGATTGCCAATACGCAAATCTACGTGCTCGACGAAGCGCTCGAGCC GGTGCCCATCGGCGTGCCGGGCGAGATCTTCATCGGCGGCGTGGGCGTCGCCCGGGGATATCA CGGGCGTCCGGACCTGACGGCCGAGCGATTCGTACCCGACCCCTTCGGGCAAACCAAAGGGGC GCGCCTGTATCGGACCGGCGATCGGGCGCGCTGGCTGCCGGACGGAAACCTCGAGTTTCTCGG TCGAAACGACGAGCAGGTGAAGGTCCGCGGTGTCCGCATCGAGCTGGAGGAGATCCGCGCGGC GTTGCTCAAGCACCCGGCGGTCGCTCAAGCCGTGGCCGTGGTGCGCGAGGACACGCCGGGGGA CAAGCGGCTCGTCGCGTATGTCGTCGGACGCGGAGGAGCGCGCGTGACCGCCGCGGAGCTGCG CCAGTCCGTGAGCGAGCGATTGCCTGCGACCATGGTGCCATCGTCCTTCGTGGCGCTCGACGC CTTGCCCCTGACGCCGAATGGCAAGGTGGACCGCCGCGCGCTGCCGGAGCCCGAGCAGAGCGC WO 00/22139 PCT/US99/23535 58 CGGCCGCGAGGACCACGTCGCGCCG-7 GCAACGCCGTCGAGGAGGAGCTCGCCAGGATCTGGGC GAGCGTCCTCCGGCTCGAAGGGT-GGCGTCCACGACACTTCTTCGAGATCGGCGGCGACTC GATCCTGAGCATCCAGATCGTGGTGCJr-GCGCGCAGCAGGCAGGGCTGCGCCTCACCCCGCGTCA GATGTTCCAGCACCAGACCATCGCCGAGCTTTCGACCGTGGCTAGAGCCGTCGAGGCGGTCCA CGTCGAGCAGGACCCGGTGACCGGTCCCGCGCCGCTCACGCCGGTGCAGCGCTGGTGGCTGGA GCAGGAGGCGGCCGAGCCGCACCAC--TTCAACCAGTCGATCTTCCTCGAGGTACGCGAGCGGCT CGACGAGAGCGCGCTGGAGCAGGCC-ATCGCGCATCTGATCGACCACCACGACGCGCTCCGGTT GCGCCTCGCGCGCGACGAACGCGGC GCCCACCAGGTCTTCGCCGCGCCGGGAGGCTCGACCCC ATTTCAGCGCGTCGACCTCGGGGCG CTGCCCAGCGCCGAGCAGATCTCCGCCATGGAGAJAGGC CGCGAGCGAGGCGCAGGCGAGCCTCG,-ATCTGGCCGCGGGCCCGGTCGTCCGCGCCGTGCTCTT CGACCTCGGCGAGGTCGCCCCGCAI-"CGGCTGCTCGTCATCGCCCACCATATTGCGGTCGACAG CGTCTCCTGGCGGATCCTGCTCGACG -ATCTCTTTGGGGCCTATGAGCAGGCGCGCCGCGGCGA GGCCGTACGCCTGCCGCCCAAGACCACGTCGGTCXAJGCGCTGGGCCGAGCTGCTCACCGAGCA CGCCGGCTCCGAGGCCGTCAAGGCGGAGCTCGGCTACTGGCTCGACTCATCGCGACGAACGGT AGCTCCGCTGCCCGTGGATCGACGGGCCGGCGAGGACGTGTGGGGCTCGGCGCGCCACATCGT CGTCTCGCTCACGCCGGAGCAGACGG AGCAGCTCCTGCGCGAGGTGCCGCAGGCGTACCGCAC ACGGATCGACGACGCGCTCCTCACTGCGTTCGCGCAGGCCATCGCTCGGTGGACGGGCTCGCC GGCGGTGCTCCTCGACCTCGAGGGTCACGGGCGCGAGGAGCTCGCCGGCGTAGACCTCACGCG CACGGTCGGCTGGTTTACGGCCATGTACCCGATCCTACTCCGCGTCGACGCGGCGGATCCGGG TGAGGCGCTCAATCGATCAGGA ;C AGCTCCGCGCCGTGCCAGGCCGCGGGCTCGGCTACGG CTTGTTGCGTTACCTTCGGTCCGA7ACCATCGCCGAGGTCCGCGCGTTGCCGCAGGCCGAGCT CTGCTTCAACTACCTCGGCCAGCTCGATCAGGCGATCCCCGAGGCTGCACCGTTCCGGCCGGC GCGCGAGTATCAAGGCTCGGAGCGC'AGCCCCGGCGCCCATCGCGCCCACCTCATCGAGGTGAA CGCGAGCATCGCCAATGGGCGCCTG--TACGCCACGTGGACGTACAGCGAGCGCCGCCACGAGCC CGAAACCATCGAGCGCGTCGCGGCG-AGCTTCGTCACGGCGCTCCGCGCGCTCATCGCGCACTG CACCTTGCCCGAGGTCGGCGGCAACACGCCTTCCGACTTCGACAAGGTGCGCCTGCGCCAGGA GACCATCGATGCTCTCGACGCAATCG -ACGCGGGCCCCGGGCCGTCTGCGAGGGGGAGCCGAAT CGAAGACGTCTACCCGCTCTCCCCCTCCAGGAGGGCATCCTGTTCCACACGCTCTACGCCAC CGATTACACGGCGTATGTCGAGCA -rnTCCACTGGACGCTGGAGGGCGATTTCGACGCCGAGGC GTTCACCCGCGCCCTCCAGGACGT -- 3TCGCTCGGCATGCCGCCCTGCGCACGTCGTTCGCCTG WO 00/22139 PCTIUS99/23535 59 GGAGCGCCTCGATGCTCCACTTCAGATCGTCCGCACGGGCGCGGTCCTCCCCGTCGAGCACCA GGACCTACGCGGCCTCGCCGCGGAGG AGCAGACCGCGCACATCTCCCGTTACTCGAGGCAGA GCGCCAGCGCCGGTTCGATCTGCGAAGGCGCCCCTCATGCGCGCCGGGCTGCTCCGGCTCCG CAAGGACGCCTGGTCCCTCGTCGAGACCATCCACCACCTGATCCTGGACGGCTGGTCGACACA AATCTTGCTCAAAGAAGTGTTCACGCTCTACGAGGCGCACCGCGGACACCGTGGGCATCTCGC GCTGGAGCTCGAGCAGCCGCGGCCCTACGGCGATTACATCGGCTGGCTCGCGAAGCAGGACCA GGTGCGCACCGCGGCCTTCTGGCGGCGCGAGCTCGAGGGCTTCTCCGCGCCGACGCCGCTCGG CGTCGACCGCGCTGTGCCGCACGACGACGGCGGCCCGCGGTTTGGTTGGCGCCGCATCGCCCT CTC,-GGCGACGACGCGGCCCCCCTCGCCGCCTTCGCGCGTCAGCATCAGCTCACGATGAGCAC GCTG-GTGCAAGGCGCGTGGGCGCTGCTCTTGTCACGCTACAGCGGCGATCCCGACGTGCTCTT CGGT-ATGACCGTCTCGGGCCGCTCGGCGCCGATTCCCGGTATCGAGCGCATGACCGGCCTCTT CATCH -AACACCATTCCGGTGCGCGTGCGCGAGCCTGCCGACGCGTCGGTGCTCGCGTGGCTCAA GGCGCTCCAGGAGCACGAGGCAGAGCTGCTCGAGCACGAGCACAGCCCGCTGGTCGAGGTCCA GGCC CATAGCGACGTGCCGCGCGGGACCCCGCTCTTCGAGAGCCTCGTCGTGTTCGAGAACTA CCCGG""TGCAGGTCATCTTCGAGGCCCCTCCGGTCGAGGGGCCGACGCGCGCGGAGGAGGGCCT CCGCATGATCGATGCGCAGTATATCAGTGATCCACCGTATCCGCTGACGGTCGTCGCGGCCTT CCA:-GGGACGCTTTATCTCAATATTGGCTACGAGCGCCGCCGGTTCGACGACCAGGCCGTCGA ACGG ATGATCGGGCACGTCACGACGCTGCTCCGGGGCTTCGTGCAGAGGCCCGAGACGTCGGT CCGC-GATCTGCCGTTGCTGACGGCCGAGGAGGAGCGCACCCAGCTCCACGCGTGGAkTGCCAC pGGCC-GCGCCGTATCCCGAGGGCCATTGCATGCACGAGCTGTTCGAGCAGCAAGTGGAGCGGTC GCC CGAGGCGACCGCGGTGCTCCTCCAGCAGCAGACGTTGACGTATCGAGAGCTGAACATACG CGC 3 -AATCAGCTCGCGCATCACCTGCGGAGCCTCGGCGTGGGCCCAGAAGTGCGCGTGGGCTT GTG-TC-TCGAACGGTCGATCGAGACGGTCGTGGCGATCCTCGGCGTGCTCAJAGGCAGGCGGGGT CTACG, TGCCGCTCGACCCGACGTACCCCAGCGAGCGCCTCGGGCTCATGATGGAGGACGCGGC GCCCTCGGTGCTGCTCACGCAGACGTCGCTCCTCTCGAGCTGCCGCCCCACGGGGATGCAAC GCT 2 G- TACAGCTCGACGCGCTGCAzCGAAGCGCTCTCCAGGCTGCCACACCATACCCCGCGGAG CGGCCTCACGGCCCAGAACCTCGCATACGTCATGTACACTTCCGGCTCGACCGGGCGGCCCAA GGGC 3 TGCTCGTCGAGCACC-GCGGCCTGTGCAATCTGCCCACCGTGCAGGCCCAGCTCTATGC AAT ICGCCGAGCGACCGG-'CTCCTCCAGTTCGCGCCGCTCTGCTTCGACACATCGTTCTGCGA GATG--CGCTCGCGTTGCTCTCGGGAGCGACGCTGGTGATGGGCACGGCGGACGAGCTCCTCCC WO 00/22139 PCT/US99/23535 60 GGGACCTCCGCTGGTCGAGCTGCTGAAAAAGCACGCGGTCACGGCGATGCTCCTGGCCCCTTC GGTGCTCGCAGCGCTGCCAGAACAACAGAGCGCGGCGTTGCCGCTGCGCGTGCTCGCGATGGC CGGCGAGGCGTGCCCGGCGGAGCTCGTCAAGCGCTGGAAGGCACCCGGACGGCGCCTGTTCAA CTCCTATGGCCCGACCGAGACCACCATTTGGGCAAGCTCCGCAGCGGACCTGTCCGACGAACG GATCCCGCCCATCGGCCGTCCGATTGCCAATACGCAAATCTACGTGCTCGACGAAGCGCTCGA GCCGGTGCCCATCGGCGTGCCGGGCGAGATCTTCATCGGCGGCGTGGGCGTCGCCCGGGGATA TCACGGGCGGCCGGACCTGACGGCCGAGCGATTCGTACCCGACCCCTTCGGGCAAACCAAAGG GGCGCGCCTGTATCGGACCGGCGATCGGGCGCGCTGGCTGCCGGACGGCAACCTCGAGTTTCT CGGTCGAAACGACGAGCAGGTGAAGGTCCGCGGTATCCGCATCGAGCTGGAGGAGATCCGCGC GGCGTTGCTGAAGCACCCGGCGGTCGCTCAAGCCGTGGCCGTGGTGCGCGAGGACGCGCCGGG GGACAAGCGGCTCGTCGCGTATGTCGTCGGACGCGGAGGAGCGCGCCTGACCGCCGCGGAGCT GCGCCAGTCCGTGAGCGAGCGATTGCCCGCGACCATGGTGCCGTCGTCCTTCGTGGCGCTCGA CGCCCTGCCCCTCACGCCGAACGGCAAGGTGGACCGCCGCGCGCTGCCGGAGCCCGAGCGGAG CGCCGGCGGCGAGGACCACGTCGCACCGCGCAACGCCATCGAGGAGGAGCTCACACGAATCTG GGCCGACGTACTTGGGGCAAAGCGGGTCGGTGTGCACGACAATTTCTTCGATCTCGGCGGCCA TTCCCTGCTGCTCGTCCGGGTGCATGATCGGCTCGGCCAGCGGTTCGATCGGCCGCCCTCGAT GGTCGACCTCTTCACCTATCCGACCGTGGCGTCGCTCGCGCGGTTCCTTGGCGAACGGGCGAA CGGCAAGCAATCGCCGAGGGAGGCCGCGGCGGACGTCACGGAGCGCGGCCGGCGCCGCCTGGA GGCGCGGGCGCGGCGGGCGAAGGCCATCCGTGGCCCGACCTGACCCGGGCACCCTTCCAAGCC CCGCCGTTCCTCGCACATCCGCCGCCTCGAGCGCCGCGTCCAGCGCCGCCGTTCGCCGACGAG GAGGCGCGAGACGACGGTCCAAGGCCTTCGTGGGCTCTTTGCCCCGCAATCCGGAAGCTGCGC GGCAGTTCGTCGCCCCTGCAATGCTGCCATTGTAGAGCTCCTCCGCTCGCCGCGGCCTCTTTT CTTGCGGCCCGTCCGCGATTGACCTCACATCCTGATCCCTTCTTGCGTCGTCCAGAAAGTGAT TGACGGCCAGCGCCGCGCTTGAGATCTTCCGGCGCGCGGCGATTTCATCGCTCCGGCGCGCCG TGACTGTCACCTGCGAAGGGATTATAATGAAACATAACATTGGGTGGCTTCTACCCGCCGCCC TCGCGACGCTTGCCTTCGTCCCGGCCTGCAGCCCGAATCACGGTGAGGATGCGCCCTCCGTGA CGTCAGCAGAGAGCGGCGCGGCGCCGAGCGCTGACTGCGTCGCGCTCGGGGCGAAGCTCCAGG CGGCGCTGGACGGCGCCGCCGCCGCGCAAAAGGCTCCGGGAGCCGCAGCGGCGGTCCAGAGCG GGGACTGTGTCTGGCGGGGCGCCACGGGCGTCTCGGACCTGGTCGCGAGCACGCCGACGAAGC CTGGAGATCTCTTTCGGATCGGCAGCATCACCAAGACCTTCGTCTCTACGCTGATACTCATGC WO 00/22139 PCT/US99/23535 61 TCCGGGCAGAAGGCCGGTTGTCGCT:CGACGACGCGGTGTCGAAGTATGTGAGGGCATCCCCG CCGGCGACCAGATGACGCTGCGCCAGATCCTCGGTCACACGAGCGGGCTCTTCGATTACACGT ACAGCCCGGCGCTCGGCCAAATGATCGAGGTGGATCCGACCCGCGCCTTCGCGCCGGCAGAGC TCATCGCCCTCGCCACGGCCGAGGCC- CCGTATTTCGCGCCCGGGCGCGGGTTTTCGCTATTCGA ACACCAATTACATCGTGGCCGGCCTG'--GTGGCCGAGGCGGTGTCGGGCGGGACGCTCGCCGGGC TGCTCCGCACGCGCATCCTAGACCCTGTGGGCCTCGCGCACACGTATCTGGACGGCGCCGAGC CGCCGGTCCAAGGGCTCATCCGCGGC TACGGCGACTACGGCGCGGGCTTGGTCGACATCACCG ACCAGCTGTCGCCCACCGAGGCGTGGGCCGCCGGCGCCCTGGTGTCGAACGTCGATGACCTCA ATCGCTTCTTTGCCCTGCTCATCAGCCACGAGCTGCTCTCGTCGGACGAGCTTCAGGACATGA CCACCTGGACCCCGACGATGTGGCCC CACGAGCCCGGATATGGCCTCGGCCTCATCGAGCGCG ATTCTGCGCTCGGCTCCCTCAACGGCACTGCGGAATCATCTGGGGCTTTCATCGGCGTCGT ACGGGGTGCCCGGCCGCGGCGACGC-GATCACCGCGCTCATCAACCGGAGCGACGGCGACGCAG CGCGGCTCGTCGACGAGCTCGCGAGGTCGTGAGAGCGCTGATCGAGGCGGAATGGGAGCG CTTCGGCGGGTGGTGATGGCGCCCG--GCGCTCAGAJkCGCGACGCGCAGCCCCGCGCTCAGCGGG CCTGCGCCGGGCGACGCGGCCACGGCGCCCGGACCGACGAGGAGCCGCGCGACGGCGGGCGCG CTCGGCGCGTCGTCTCGCCGCACCCGCCGCTTGCCGAACACGTAGAGCGGCAGGCCGACGGCG ACCCCGGCCACCCCGCCGAGCGCGGTGGCGATCGCCACCTCGGACGCCTCGGCGCGCGCGGCG CTGCTGTCGTCGTGGCTCGCGAAGACCAGCACCGCGCCGCTGAGGATGGCGGCGCCGCCCAGG GTCGTGAGGACGAGCCCCGAGATCACCATGACCGGGCTGTTCCACTCCGTCGTCCGCTCCTCG AAGTCGCGGAACGCCGCCCTCGCC-GC-CGCGAGCTCCAGCTCGATCCGGCGCTGCTCGGCGCGC CGCTCGTCCGCGGAGCCGATCTCGTGGACGCGGCGGGCCTGGCCCTCCAGCGCCGCGATGCGC GCCTCGTGCGCGGCGGCGGTCTCCTC'-CCACGTGGCCCCTGGCGGGACCCCCGCCACGGCCGGC GCGACAGAGGGCGCCGACGCCGGG27TCGAGGCGGGCGCCGCGGGCGGCTCCGCGGCCACGGAA GGCGCCGCCGCCGCGGGAGGCGCGG-GCGGCTCCGCGGCCACGGAAGGCGCCGCCGCCGCGGAA GGCGCGGGCGACTCCGCGGCCACGG-,AGGCGCGGCCGCCGCGGGAGGCGCGGGCGGCTCCGCT GCAACGGAGAGCGCGGGCGCCGCG"7CAGCCAGGCCCAGCGCCCACGCGACGACACGACGGCGC GCCGCAACCGCGCGCGGGCGCGCGAAGCGGAGGTGGACCTGCTCCATGCGCGCAGCGTCGCCC CTGCGGCGTAGCCI-GGCCAACCAACCGGCCGAA AGGCGCGCCGGCGGCCCGCGCGGCGG7CTCGCCGCTCACCCCTCGCGCGGCCGGCCGCGGCGCC GCCTCCCCTCCCCGGCGGGCCGCOG--TCGGCGGCCACGCGGAGCAGCTCCTGGAAGTGCCGCT WO 00/22139 PCTIUS99/23535 62 CCACCGGGCCGAGGTCGATGCCGTCC-ATGACGACGTGAACGCGAGTACGGCAGCAGCGTCT GCCAGGCGCGCAGCCAGCCCGGGA23TAGCGCGGCCGCTCCAGCACGCCGGCGGCGCGCAGCT CCGCCAGCACCGCGATGTCGTCGAG 03 CGAT CCGGCCG CACACGAGCAGCTCCACCTCGTCGC GCGCGCCAGACCGCGAGCTGCTGGACCGCGTG AGGCGTCCTTGGTGAACGGCGCGC 'CC CCTCGACGAGC CCGCCGCGGCACACGCGCTGGGCGT CGAAGTAGGCGTCGCGGCGCTCGGCGCCGCGCTCGCGCAGGTGCCGGTACAGGTCGAGGAAGC TCGCGCCCTGCTCGGCCATGTCCAC-GAGCCGCACCCGCTCGGCGAGCCGGGTGAGGCGGCCGA TGGAGAGCGAGCGGCTGTAGAGCTCG- -GCGAAJGATGGCGAGCCCCTCCTGCGTGCGCGTGGTGC GGGGGCCGCCCGAGCGCAGGAACGCGC3(-ACCG CGGCTGC GCCGCGCCGTTGTGCGCGGTGAGCG CGTGCGTCTCGACCTCGTGGTGCCACAGCCCCTCGGCCTCCCACGCCGCGAAGGTCGCCTCCG GCCGGATGCGGACCCGGCTCATG -C CCGCGACCACCTTGGCCGTGACGCGCGGGTCGACGGTGA TCTCGAGGTCGAGCCGCGGCGCCCG-73000 GCCACGCGGGCGGCGAGCATGTCCCGGAGCGCGC CGGCGTCGAGCGGCTCCTCCTCGGGATCGCTGGCCTCGTCCCAGCCGTGGACGCGCAGGCGCT CGGTGAGGTGCTCGGCGAGGTCGAT3TTCCTGAGCGAGCCGCCGAGACCGCGAGCGCGCGC CGCCGTAGAGCTCCTGCGACCGCGCG---GAGAACGCGCGGGTGCCCGCGGCCTCGAGCAGCTCCG CGGCCTGGATCTGCGCGCGGACGT7rnGTCCCGCAGCCAGCCGAGCGCCGGCGCGTCCCCGTCGA TGGCCCCGAGGAGCTCGCGCAGCTCG GCGACGCGCCGCGCGAGGCCGTCGCGATCGACGCGGT ACTCGACCTCGGGGAGGCGGTCCTCC,-CCGGCGGCGAAGAGCGCTCCTCCACCTCGCGCGGCC AGGCGATGTCCTCGAGCAGCTTGAGG- -GCCTTGCCCTCCGCCAGGCGGCCGCCCACCCGATCGA GCTGC-TCCAGCACGGCGCG0TCGA03 -CTCATCGAGCGCAGGATCGCCGAALCCGCGAGACGCC GGAACCGTCATTCCCTCGACGAGGCAz-GCGATTGCCATGTTCCGTCGCTTTTTGGAGCGCCGTC GTCGCGCTCGCCTGCGGGCTCCGGC-GATCCAGCGCGGTTGCATGCAGCGAGGGTGTTCCGGGG CTGGC-TCGAGAGCGTCCTTTGGCCCAC ACCCGAGACACGAATGCTCCGCGCCGAGCGCGGTTG ACCGTGGACCCGCCGGAGAGCCGA: 3-ATACGGTCCGGCCGATGTCGGAGAGTGTAGCTCAACT CGAAG AACACCGCGCGGCGCTCAC C CG7ACACTGCTACCGGATGCTGGGTTCGGTGGTCGACGC CGACGACGCCGTCCAGGAGACGA7TC 3-TGCGCGCCTGGCGGAGCCTGGATAAGTTCGACGGGCG CTCG'-CGCTGCGCACCTGGCTGTAC CGCATCGCGACGAACGTCTGCATCGACCTGCGGGCCGA CCGC-GC'-GCGCCGGGCGCGCCCCA-TCC7AGGAAGGCCCGGTCGGCACGGTGGACGACGCGCTCGA GACGC-GCCCGCGCACCCACTGGC:CGAGCCCGTCCCCGACGCGCACGCCCTGCCGGCGGACAT CGACCCCGCGGAGCGCGATGCT-C CGCCAGAGCATCCGCCTCGCGTTCGTCGCGGCGCTCCA WO 00/22139 PCT/US99/23535 63 GCACCTGCCGCCGAAGCAGCGCGCCGCGCTGCTGCTCACGGAGGTGCTCGGCTGGTCCGCCGC GGAGGTCGCCGACAGCCTCAACACCTCGGTCGCCGCGATCACAGCGCGCTCCAGCGCGCGC G GGCGACGCTCGCGAGCCGCGATCTCGGCGACGCGCGCCCCTCGCTGCCGGAGCCGCAGTCCGC GCTGCTCGACCGCTACGTCAACGCCTTCGAGCGGTACGACGTCGACGCGCTCACGGCGCTGCT GCACCAGGACGCGACCCTGTCGATGCCGCCGTTCACCCTGTGGCTCCGCGGCCACGAGTCGAT CCGCGCCTGGCTCGTGGGCCCGGGAGCGGGCTGCCGCGGGTCGCGGCTCATCCCGACGGCGGC GAGCGGCTCGCCCGCGTTCGCGCAGTATCGC.CCGGCGCCGGAGGGCGGCCACCGGGCCTGGGC GCTC'ATCGTCCTCGACGTCGCGGGGGACCGCATCGTCAGCATGACGTCCTTCCTCGACACCGA GACGCTCTTCCCGCGGTTCGGCCTGC CGCTCGATCTACCGGCGTAGCCGCGGGCGCCCTGCCT pGCCTCGCCGCGGGTGCCC'TGCCTGCCTAGCCGCGGGCGCCCGGCCTGGCCACGGGCGCCCGGC CTGG CCACGGGCGCCCGGCCAGCGACGGGGCGACGATTTTTTTCTGAGCGACCGATGAGTCCT GACGGGGCCGGGGGTCTACGGGGGTGAATCCAACACGGAGGCACCCATGACCGTGACCATCGC CAGC-ATCGATCATCGTGACCAGGACCTCATGACCGGGCCCCAGGCCAJAGGCGCCGGCCCGCGC GGCG-GCGCCCGACGCGGCGCCGTCCAGGCGAGCCGTGTGGGCGGGCCGCGTCCTGAGCGGGCT GGCCACGCTGTTCCTGACGTTCGACGCCGCGGTGAGGTGCTGAAGCTGTTCCCCGCGGAGGC GTCGACCGCCGAGCTCGGGTTCCCGGCGCACCTCGTCCCCACCCTCGGCTACCTCCAGATCGC TTGC'-TCGTGGCCTACCTGATCCCGCGCACCGCGGTGCTCGGCGCGATCCTGTGGACCGGCTA CCTG7GGCGGCGCGATCGCGATCCACGTGCGGGTCGAGkAkCCCGCTCTTCAGCCACACGCTCTT CCCC ATCTACGTCGCCGCGTTCCTCTGGGCGGGGCTCTGGCTGCGCGACCGCCGCGTGCGCGC GCTGACCGCGAGCCCGTCGTCGCAGGGCCGATGAGCTTCACGTTTCACGAGAGTCCATCACGG TAAAGGAGAAGCGAGCCATGACCACAAAGACCCCCCGCAGCTCTTCGTCACCTGTCCGTC CGCG,"ACCTGAAGCGATCGATGGAGTTCTTCAGCAAGCTCGGGTTCGAGTTCAACCCGCAGTTC ACCGACGAGAAGGCCGCCTGCATGGTCGTCAGCGAGGAGGCCTATGTCATGCTCCTCGTGGAG TCGT-TCTTCAAGACGTTCATGAGAGGAGATCTGCAGCACGAGCACGCACACGGOAGGGCTC TTC -- CGCTCTCGTGCAGCAGCCGGGCCGAGGTCGACGACATGTGAGAAGGCGGTCGCGGCG GGCGG-GTCGCACGCGATGGATCCGCAGGATCACGGCTTCATGTACGGGTGGAGCTTCTACGAC GTG- ATGGCCACCACTGGGAGGTCATGTGGATGGATCCCAAGGCGATCCAGCCGTAGCCGACG GGCT-GGGCGCGCCGCCTGGAAGAGCCCCCGTGAGGCGGGGAGGCGGGAGGATCACCGTCTTC GT-_: -CCGGTCGACGCCGTCTTGACCGTTAGGGG CACAGCGCGTCGCAGGTGATGCCGAGCCGCAGCAGCGACACGGGCACGAGCGTGGCTCCGATG WO 00/22139 PCT/US99/23535 64 GAGATGAGCCGAGTCTCGCCCATGGTCTCGGGGTCATGAATGGATGAGTAGGGGACTCGCTCC TTCCTCACGTCGTGCTCGACGGCGACGGCGAGGCCGAGCTCGAAGTGCACGGGGCCTGGACCG AAGATCCAGCTCGCCCCGGCGCGAGCCCCGACGAAAAGCGTGTCGCCGTCGACGCCAGGGCCG TCGTCCCAGCCGGGCGATCCCACCGCGGTGTAGGTGTGTTTCCCGAAGGAACCCGCGAGCGAG AGTCGAAGTCCGACCGGCGCTCGCCACGCGACGCCCGCTGTCGCGCCGACGCCGCCGAAGCTC TCCCCGAAAGGCTTATCCCCTGTCTCGATGAAGCCACCCACCTCGATGACGCTGATGCGGTAC GTGAGCGCGAGATTGAGGTGCACCCCAGCGCTGTCCGAGCCCGAGTAGAGGCCGGCGCCCACC TGCACGCTGAAATCCATGCTCGGCGCGGATCCGCGCGCAGGAGCGACGCCAGGGGCGCTGCCC TCCTGCGCGCGGGCCGTCCCGACGCAAAGAAAGAGGGCTGTCGCGAAGAATCCAAGCGAGATC GATCGAAGTGAGCGCATGTCGGGCCCTGGAGCATCCGCTGTACCAGGTGCGTCGTATTCATGC GGCGCGCCGCCGGGCGCCGCCGCGCTGGCCTGTCCGACGCGAGATCACGAATCCGCCATCGCT CCCCTGGGCCGCCGGCCGCTCTGGTTCGCCTGCGGGCGTGCGCCGGCGCTCGTGTGGCCCATG GCAACCTTGTCGCGGTGTCGCTCGAACAGCACAGAGAGTATCGCGTCCGCAACAACCGCGCGA CCCGGCGAGACGCTCGTGGGGCCCCCTGCCTCCCCACTTCATCATAACGCCATCAGGAGCACT CGACATTTCATTTCTTCACCTCCACTGGCTGAGGGCGACGGTGCTCGTCATCGGCCGGTTGCT CTGGCGGTTGCTCTGGCGGGGTTTCTGACGCCCGGAACTAACGCTTCGAGCGCTCCCCCTTGC TCTCCCGTTCCTTCAGCTCCTCCAGCAGGTCGTCGAGGCGCTCGTAGCTGCCTTCCCAGAAGC GGCGGTAGTTGTCGAGCCAGCCGCTGGCGTCCTCGAGCGGCTTGGCCTCGATCCGACAAGGCC TCCGCTGCGCGTCGCGGCCGCGCGAGATCAGGCCCGCTCGCTCCAGCACCTTGAGGTGCTTGG AGATCGCGGGCTGGCTCATCGCGAACGGCTTCGCCAGCTCGGTCACCGACGCCTCGCCGGACG CGAGGCGCGCGAGGATCGCTCGCCGTGTCGGATCGGCGAGCGCAGCGAACGTTGCGTCGAGGC GCTCGGACGGGGTCATTGCATAACTCCTTGGTATAAAAACCAGTTAGTTATACAACCTGGGGC CCGGGCGGTCAAGCCTCCAGGCGATGGCGGTTCGGCCCGGGGGCTCCGCTCGCGGCACGCGCG CCGCGCGGCTACGTGCGCGGCGCGGTGAGCACGTCCTGCAGCGTGGCGCCGACCACGGGCTTG GTCAGGTGCAGGTCGAAGCCGGCCCGCCTGGACCTGGCCTGATCGTCGGGCCCGCCGTAGCCC GAGAGCGCCACCAGGTAGAGCGCTTCGCCGCCGGGCGCGGCCCGCGCCCGGCGCGCGACCTCA TAACCGTCGATGCCGGGCAAGCCGATGTCCACGAAGGCCACCTCGGGGCGCAGCTCCAGAAGC TTCTTCACGCCCTCCAGCCCGTCCACCGCCACCGTCACCTCGTGCCCCAGCGCCTCGATGTAC GCCCGCATCACCCGGCGCACGTCCTCCGCGTCCTCCACGACGAGCACCCGGCGCCGGTCAGCC GCCGCCTCGGGCGCCTCGGCGCGCTGCGCCGGAGGCGGCGGCGGCTCGTCGCGCTGCGCCGGA WO 00/22139 PCT/US99/23535 65 GGCGGCCCCTCGCGCGGCGGGGGCGGCCCGGCGCTCGGGGCAGGCTGCGGCGCCGCCCCGGGG CCGAGCGGCAGGCGCACGGTGAAC:CGCTGCCCTGGCCCGGCCCGGCGCTCGCCGCGGCCACG CTGCCGCCGTGCAGTTCCAGGAGCCGCCGCACCAGCGTGAGCCCGAGCCCCAGCCCGCCCGTG CTCCGGTCGATGGTCTGGTCGACCTGCGTGAACAGATCGAACACCTTCTCGAGCATCGCCGCC GGGATGCCGCGGCCCGTGTCGCGCACCCGCAGCACGGCCTCGGGCGCGCCGACCGCCGCCTCG CGCGTGAGGCGCACCGAGATCGAGCCCCCCGGCGGGGTGTACTTCGCGGCGTTGGTCAGGAGG TTCGTCACCACCTGCTCCAGCCGCGCTCGCGTCGGCCCGCATGCCGAAGTCCCCGGGCCCCACC GACAGCGACACGTCATGGCGCCGGG CCTCGACGGCCGGCCTCACCGCGGCGGCGGCGCTCTGC ACCACCGCCGCGAGATCGACGTCC: CGAGGCGCAGCTCCACCGTGCCCCGCGTGATGCGCGAC ACGTCGAGCAGATCGTCGACCAGCCGCACGAGGTGGCCCATCTGCCGCCGCGCGATCTCCCGG TAGCGCGCCGACGCGGGCCCGTCG CCGTCCGCGTCGTCGAGCAGCGTCAGCGACAGGCTGATC GAGGCCATCGGGTTCCGGAGCTCG:CGCGAGCATCGCGAGGAACTCGTCCTTGCGCTGATCG GCGAGCTTCAGCGCCTCGACGAGCGCCTCCACGCGCCTCCGGGCGCGCACCTGGTCGGTCACG TCGAACGCGAACACGAAGACGCCCTCGACCGCCCCGTCGCGATCGCGCATCGGCTGGTAGACG AAGTTGAAGAACACCTCCTCCGTCGTGCCGTCGCCCCGGCGATCGAGCCGCACCGGGAGCTCC TTGCCGACGATGGGCTCGCCGGTGCGGACCACCGCGTCGAGGAGCTCCCAGATGCCCTGTCCC TCGAGCTCGGGGAGGGCGGCCCGGATGGGCTCGCCCACGAGCGATCGACCGCCGACGAGCCGC TGGTAGAGCGGGTTGACCACCTCGAGACGTGCTCCGGCCCGCGGAGGATGGCGATGGGCCCC GGGGCCTGCATGAAGAGGTCGTTCAGGTACTGGCGCTGCCCCTCGGCCTCGCGCCGGCGGCGC GCGAGCTCGACGTGGATGCGGACCCGCGCGAGGAGCTCCTTCGCGGAGAACGGCTTCACGAGG AAGTCGTCGGCGCCGGCCTCGAGGCTGTCGACGCGCGCCTCCTCGCCCGCGCGCGCGGAGAGC ATCACCACGGCGACGCCGCGGGTG CGATCGTCGGCGCGCAGCGCCCTGAGCAGGCCGAAGCCG TCGAGCCGCGGCATCATCACGTCG-TGAGCACGAGATCCGGCGGGTGGGCGCGGGCGCGCTCC AGGGCGGCCCGACCGTCGGCCACG-CCTCCACCGTCCACCCCTCCGCCACGAGCAGCCGCAGC * GCGTACTCGCGCATGTCCGCGTTGCGTCGGCGACGAGGACGCGCCCCGGCAGCCTCCCGGCC GGCCCCTCGCCCGCCGGCCGGGACCCGGCGCCTGCTCGCCGCGGAGCCACTGCGCGGCCTCG TCGAGGAAGGGCGCGGCGTCCCGCC CCCCCGCGGCCGGCGCCGAGGCCGGCGCGAC or its complementary strand, WO 00/22139 PCT/US99/23535 66 (b) DNA-sequences which hybridise under stringent conditions to regions of DNA-sequences according to (a) encoding proteins or to fragments of said DNA-sequences, (c) DNA-sequences which hybridise to the DNA-sequences accord ing to (a) and (b) because of a degeneration of the genetic code, (d) allele variations and mutants resulting by substitution, insertion or deletion of nucleotides or inversion of nucleotide segments of DNA-sequences according to (a) to (c) , wherein the variations and mutants offer isofunctional expression products. 7. DNA sequence according to claims 1 to 5, wherein the DNA is selected from the group consisting of (a) the following DNA Sequence: Seq ID No 2 (>pEPOcos6 region) GGATCACCTGCGGCGCGATCGCCGACCTCGTGCTGGTGTTCGGCTCGCTGGATGAGAAGCCGG CGGCGCTACTGATAGAGACGGCGACGCCCGGGCTGCGGGTGGAGCGGTTGCGGGAGATGCTCG GCTTTCGGGCGGCCCACCTGGCGAAGCTGTCCTTCGACGGTTGCGAGGTCCCCGAGGCTCAGC TGATTGGCCGGCCCGGCTTTGCGCTGATGTATCTGGCCCCCTACGCCCTGGATTTCGGTCGGG TCAGCGTCGCCTGGGCCTGCCTGGGCATGATCCGCGCTTGCCTGGAGACCTGCGCACAGCACA TCCTCACCCGCCGCACCTTCGGCCACCTGCTAGCCGATCACGGCATGATCCAAACCCTGATCA CCAACCTGGGGATTCACCACCAGGCGACGCTGCTCCACACGCTGCAGGCCTGCCGCGCCAGGG ATCGCGGCGACGTGACCGCCTCCGAGGCCACCCTCGCCGCCAAATACCTCGCGTCGCGGACGG CGGTCCAGGAGACGACCAACGCGGT CCAGATCATGGGCGCGCTGGGCTGCGACGAGGAGGGCG CGATCGCCCGCCACTTCCGCGACGC CAAGACGACCGAAATCATCGAAGGCAGCAACCAGATCA TCGAGGCGCTGCTGGCCAAGAACATCGCCCGCGCCGGTCGCGACAACTATCGCCGCTTCCTCG WO 00/22139 PCT/US99/23535 67 ATGCGGAACTCGAGCCCGGTCGGGCCGGAGGCGCACCATGACGAGCGCGGTCCCGACGCGTCA AACCAGCCTGCTCGACGACTTCGAGCGCGTCGCCGACGTCGATCCAGAGCGGATCGCCGTCCA CCCGAGCGAGACGAGCCTGCGCTATGGCGACATGAATGCGCGCGCCAACCGCATTGCCCACGG GCTACGGGCGCGCGGGATCGGGCCCAATCAAATCGTGGCGGTGGCGATGGCCCGCACGCCCGA DGCTGATGATCGTGCTGTACGGCATCCTCk2AGGCCGGCGCGGCCTACATGCCCATCGCCCGCGA CGCGCCGCCGCTGCGCCGCGATCATATGCTGCGCGAGAGCCAGGCTGCTCTGATGATCGCCGA CGAAGAGATCGCGGGACTCGCGGCCCGGGTGCTGACGCCGGCCGACCCGTTCTTCGCGGCCAT GCCGGACCACAACCCCGAGCCGCGTCACGACCCGACCGACCTGATTTACGTCATCTACACCTC GGGCTCGACCGGCCAGCCCAAGGGCGTGGCCATGGAGCACCGCGCCGTGTGGAATCGCCTGAC DTTGGATGCAGGCCCAGTATCCAATCGACACGCAGGACGTGATCCTCCAAGACGCCGATCGT CTTCGACGTGTCGGTCTGGGAGCTGTTCTGGTGGCCGCTGGCCGGCGCCTCGGTGGCCCTGCT GCCGCAATCCATGGAGAAGTTCCCCTGGGCGATATCGGCGACGGTGGCGCGGTGCGGGGTGAC GGTGATGCATTTCGTACCATCGATGCTGATGGCCTTCCTTCAGGTGGTGGCGGGCCGGCCCGA GATGGCGGACCAGATGAAGGGCCTGCGCTACGTCTTCTGCAGCGGCGAGGCCCTGGCGCCGGC DCCACGTGTCAGCCTTTCAGGAGCACATCAACCGAGCGGGCAGCATCAGCTTGACCAACCTCTA TGGACCCACCGAGGCGGCGGTCGACGTCAGCTACTTCGACTGCCCGCCCGGCGCGTCACTCGC GCGGGTGCCGATCGGACGAGCGATCACCGGCATCCAGCTGCTGGTCATGCGCGACGGCGTGCC TCAGCCCCCGGCGTCGAGGGTGAGCTCGCCATCGGCGGCGTTGGTTTGGCGCGCGGCTACAT CTCACGGCCAGACCTGACCGCCGACCGGTTCGTGCCGCATCCAGGCGGCGACGGCCAGCGGCT CTACCGCACCGGCGATCTGGTGCGCAGGGACGCGGACGGCGAGCTGGTCTTCCTGGGGCGCAT CGACCATCAGGTGAAAkATTCGCGGTCTGCGCATCGAGCCCGGGGAAATCGAGGCCCAGATCAG CGCACCAGGCGCGGGTATTGGAGCCGACCGCA GCTGACCGCCCTACATTGTCGTGGCGCGACCGGGCTTGACCCGGAAGGCGCTGCTACAGTTCCT GGGCG7CGCGGCTGCCCGACTACATGCTCCCGAACCGCTTCCTGACCCTCACGGAGCTGCCCGT DGACCG CCAACGGTAAGCGCGACTGGCGCGCGCTGCTCGGCCCGCTCGAGACCCTGCCTCTCCC TTTCTCCTGAATCCAACCAATACGAGGGATTCATGTTACACCCGATTCCCACCGACCGTTTCG CCCTGAGCCGACCGCTCTTTCGCGGGTACCTCGCGCACGATCCGATCGTGCAGGGCGTGCTGG CGGGC-GACCATCCAGGCTGGGTCCTGGTGGACCGCGAGCCCGAGCCGCGCACGGCGCTGCTGT GGGC-CTTTTCCGATCGGCTCTTCTGCGTGGGCGCAGCTGACACGCTGACCCCGCACGCCCTGG CCGAG-CTGTTCCACGACCGACTGATCCCCCAGGCCCGTA.GATCGGGCAGCCGTTTTTCCAGG WO 00/22139 PCT/US99/23535 68 TTCAGGGCGAGACGGTCGACACCTGGTCGGACCACCTGCATCAGGTGTCGCCGCACGCGACAG TCTCCTTCCGCCAGGCATTCCGCTTCGACCGCGACCTCTTCGAGCGGCTGCCAACCAAGCCGG AGCTGGCAGAGGCGCGGCTCGTGCCAATCGACGCGCGGCTGCTGGCCGAACAGGCTGATCTGC GCGAGCGGATACTGGCCTCCTGGTCCAGCGAAGCTGCCTTCCATGCGCGCGGTTTCGGCTTCT 5 GCTACCGCGTAGGTGACCAGCTGCCGAGCGTGTGCCTGGCATCGCACGTAGGCGGCGGCGCGG CCGAGCTGAGCATCAACACCGAGCTCGAAGCGCGCAATCGAGGTATGGCAACGCGGCTGTGCC GGCGTTTCATCGCCGAATCGCTGCAGCGCGGCCTGACGCCTTGCTGGGGCACCGAGACCTTTC GCCTGCCGTCAATCGCGCTGGCCCAGAAGCTCGGTTTCATCCCGACCTTCACCTTCCCCACCT ACTGCTTCGCGACCGGCACCGAACAGCCGGACGACAACTTCCTAGGCGAGCTGTACTACAGGG 0 AATCGCGCATCGCCGGAAGTGGGACCGATGAGCCGCAAGCGGTTCGGCTGGCGCGGGGTTGGA GCCTGGCCGGCGACACCGAGCGTGCCGCGAGCTTCGCCGCACGCGCCCTGGCCGAAGGGTGGG CCGGCCACTCGACTCTGGCCACCGATCCGGATTTCGCCCGATTGCGCGCCAGCGCCGCCTGGC CCCGCCTCAATGTCCCTTGAAAGGTCACGTGGACTCATGATGTCCCCTTGAAAGGTCACACTC CGAGTCATGATGATTTGTCACTCCCACCGCTTCATTTTCCTCCACGTTCCCAAGGTCGCCGGC 5 ACAAGCGTCAAGGACGTCCTCGGCCAAGAGCTATTCCAGGAGGACCAGGTCACGTTCCAGATC GCTCCCAATCCCCACTACCCACCTGAATGGACTGCGCCTTACGAGGAGCACATTATTGCCGCT GAATTGAAGAGCCAGTTGGCGCCGGAAATTTGGGACGATTACTTCAAGTTCGCCTTCGTGCGC CATCCGCTCGACTGGGCGGTCTCCAATTACTTCTTCTTCCTGCGCGACCGCAAAGGCCATCCG GCCCACGAATTCCTGGAGCGGAAGGGCTTCGCCGGTACCATGGACATGTTTTTCGGAGCGGCC D GGGCGCCATCCGCTGGTCGCCGGCATGCGCTTCAGCCAATGGGAGTTCTTGTGCGACAGCGAG GGCCGGACGCTGGTGGACTTCGTTGGCAAGTACGAGCGGCTCGAGCAGGACTTCGCCGCCGTG TGTATCCGCATCGGGCTGACCCCGCCCGACTTGCCGTGCCTCAACCAGACTCGCCACCAATCC TTTACCAGTTACTACGACGAGGCTTTGATGCGCCAAGTCAGCCGCGCGTTAGCTCGCGATTTC GAAATTTTTGATTATGCCTGAGGCGGACCCGTTGCTTCGCCACCGGTGGATTATTCGATAAGT TATTATATTTTCAGTTGATCATGTGAATGTCGATCCAGCCAACGAGGAGGATACCTCCGCGTG CGGCTATGGGGGCGCAGAGGTCACGACTACGTGTAGAAATTTGTCGAACACACCACTAGCTGC CACCGATTGGGAGCTTTGACTTGAAGATGAAAGTGGACAAGCGGAATGTCGACGACATTCTCG GACTCACTCCGACACAGACAGGCATCTTGTACCACTACCTGCTGGACCCGCAGGCCGACGCCT ATTTCGAACAATTGACGCTGCACCTGGAGGGGCCGCTCGACGTAGCGCGCTTCCGCCGCGCCT GGGAGCGCGTGGTGGCGGCTCACGACCAGCTGCGCGCCGTGTTTCGCTGGCAAGGGATCGAAC WO 00/22139 PCT/US99/23535 69 ACCCGGTGCAGATCATCCTCAAIGCAC--CACGTGCCGGACCTGGAGTTGGCGGAGGTCCCGCGCG ACGCCGATCCGGCAGCCTTCCTGGCCC--ATGGGTCGCGGCCGACCGGGCGCGCAAGTTCGACT TCGAGACGGTGCCCTTTCGCATCGGCC TCTGCCGGACTGATACCCAACATCACGTGATGCTGC TCAGCAATCACCATATCCTGATGGACGGTTGGAGTACGGGCCTGATTCTGCGGGACTTCCTCG CCTGCTACGGCGACTCCGAACTGC'-CGGCCACGCACCCGAACGCACTTCAGGCGTTCATCA AGTGGCACCAGAACCGGCCACGCCG GGGCGAGGAGCGATTTTGGCGCGACCTGTTGCGCGATG CGCCCGACGGCGGCTTTCCCCGCCTGI-GGCGTCGAGAGCACCCGCCACTCGCTTGACTTCG GCGCCCGCAGCCGCGCTCTCGACGACC, GCTTGACCCAAGGCTTGCGCGACATGGCTCGCGACC TCGACGTCACCCTCGCCGCGATGCT CCATACCGCTTGGGGCCTTCTACJTCCAGCGCTACCAGA ACAGCTGCGAAGTGATATTCGGGACC-ACCGTTTCCGGCCGCAACGTCGAGCTCGCCGGCCTCG ACGAGGTGGTCGGCTTGTTCATCAACACGATTCCGTTCCGCTTCTCGGCCGCGGCCGCGACGA CGCCCGTCGAGGCCTTCCGTGCGGACAGCGCATCTGCTGGCGAGAGCGAGTTCGAAGCCA CCCCGCTGGTGGACATCAAGGGCTGCAGTGGTCTCGGTCCGGGCGCGGAACTGTTCGACACCA TCCTGGTCATCGAGAACTATCCCT: GGACCGCGCTATCTTCGAGAGTGATTCCAGCCTGCGGT TGACCGACCACCAAATCTTCGAGCGCACCAATTACGGGCTGACCCTGACCATCGAGACCTTCA GCCGGTTGCACGTGACGCTAGCCCATCGCCGTGACCTGCTGGGCGACGCGGCCGCTGAGCGAA TGCTAGATCATTTCACCGGCCTGCTC \-CAAGCCATGCTGCGCTTCCCTCACCAGCCGTTCGCGC GCCTCGAGATGAAAGCGAACACGAGGCCCACCGCGTCCTGCACCACTCACCAACGCGTC AGCCGCTGCCGTCCCAATCGGCTT7TCCACCAGTTCTTCTTCGAGCAGGC CCAGGCCGATGGGG CACGACCGGCGCTGTGGTGCGGCGC C -ACGCGCTGOAC CTACGGCCAGC TGCAACGTGCCC TGCGTCTGGCGGGACGGCTGCAGGAAGCCGGCTTCGCCCGAGGCGATGTCGCCGCCGTCAGCC TCGGCCCGGTTCCGGATCTGATTCCC-GGTTTGCTGGGCCCGCTGTTCGCCGGCGGCGCCTACC TGCCGCTCGATCCCACCCTGCCGGC C'-CAGCGCTCGCGGTTCATCCTCGACGATGCCGGTTGCC GCTTCCTGATCAGCGACGCGCCACm-CGCGGGGCCCACGCCGATCCATCCGGACCCTGCCGGCG CCAGCCCCGTTGACGTCATTTTTGCCTGTCAGGACGGCGCCGCGCAGCCCGCCTACCTGATCT ACACCTCGGGCTCCACCGCCCACC C-AAACGCGTCTGGGTTAGCCACCGCAACCTGATCAACT TCCTGACGCCATCAGCGCAATCCTCC1('CGGTCGCCGCCGACCACCTGTTC CTCTCGCTGACTA CCGTGTCGTTCGACATTTTCGGC'"CGAGACGTGGTTCCCGCTCAGCCGCGGCTGCACGATCG TCTTGGGCACGCGCGCCGAGCAGT:GG,-ACCCGGCCGCGCCTGCCAAGGC CATCTCCTGCCATG GCGTCACGGTTTACCAGGCGACGCCA-zTCGCGACTCCACTTCAACTGGAGCACCCCACATTTG WO 00/22139 PCT/US99/23535 70 TCCGCGCCATCGGCTCCCTGACGACCCTGCTGGTAGGCGGCGAACCCCTCCCAGCCGAGCTGC TGCGGCGCGTACGCGAAG( TGACCGATGCGCGTATCTTCAACCTCTACGGTCCCACCGAAACCA CCATCTGGTCCACAGCCGG GGAGGT-CACCGCGGCGGACGTCCCGGATATCGGCCGCCCGATCG CAAATACCGGCGTTTTCCTTCTGG -CGCGAGACGGCTCGATCCAGCCGCCGGGCCTGGTGGGCG DAGTTGTGCATCGCCGGCGAGGGCGT7GGCGTTGGGCTACCACCGACGGCCGGACCTGAACCGAG AACGGTTTCGCGAGATTCCGCCGG ZCCCCTGCCCTTTGCCGGCAAGCTCTACCACACCGGCG ACCTGGCCCGCTGGACCGIAAGACGG- ACGGCTCCTCTGCCTGGGCCGTCTGGACGACCAGCTCA AAGTGCGCGOCCATCGCGTCGAGC CG"GGCGAGATCGAGGCAGTGATGGCGCGCCACCCGGCGG TCACGCAGGCGGTGGTCGTCACGCGG1-CCGCGCAJACGGCGAGCCGGTCTTGGTCGGGTTCTGGA DCTGCGGAAGGTGAGCCGATGCCAGAGGAJAGCGCTGAGCGCTTACCTGGCCGACCGACTGCCGA GCAAGTCCAC-ITC- -TAGAGCTCGTACGACGAG TCGACCGGCGCGCCCTAC CCAATC CC-TTCGCCTTGACCGAGTCGACCCGGCAGGCGGCGCCGC GCACCTTGGCCCGCACCGCCGGCGAGCATCGGGTTGCCGAGCTGTGGCAGGCCTTGTTGCGAC GCGAGGCGATCGGCTTGGACGAAC C CTTTTTTCAGGCCGGCGGGAACTCATTCGGCTTGATTC GGCTTCACGCCAAGCTGGAATCCGC-rCTTCGGGAAGTCGTTCCCGATCACCGATTTGTTCCAGC ATACCAGTATTCGCAGCCAGGCAGAATGCTGAGCGGCTCTCCGTCGAGGCGCCGCTCGCGG GAGCCGTGCCGCACCCCCGGCCG-CGCCGCCCAAGTTGCCTCCTCGGCAGCTAAATCCCCAG GGGAGCGCGGCGCGGCAGCGACGTCGAGCGGCCTGACCGCGCAACCGCCCCAACCCCACTTCC GGCC -CATCGCCGTTATCGGCCTCGCCCGGCCGATTCCCCGCCGCACCCGACCTCGACGCCTTCC TTGAACTGCTCACGGAGGGTCGCTGC -GGCATTCGCtTCTTCAGCCAAGCCGAGCTGCGCGACG AGGG-:TCTCGACGCGAATCGAATCGC GTGTCATkJACTATGTCCCGGCCAAAGGTTTCCTCGACC GGGCCGACCACTTTGATGCCGAC-1rnCTTCGGCATCCCGCCGCGCGACGCAGAAAJTCACCGATC CGCAAATTCGGCTTCTGCTTGAGTGC7 -TGCTGGAACGCGCTGGAGCATGCCGGCTACCCGCCCG GCG GCGGCGAGATCGGGCTCTTCCC"-CGGCTCCTCGGCCACTATCACTGGCTCGAATACGTGG GCTTCAGGGA-CAC-ATGCTAGTCALCAAAGCACG CCACG-CGGATCGCCTACCAGCTCG rn-TTGAGGGCATTGCCGTCACCGTGCACGGCCTGCT CGTC--GTCGCTGACCGCGGTCGAGCT-GGCCTGCGATGCGTTACACGCCGGCCGCGTGACCATGG CTTTG~rGCTGGTGGCGTTGTCTGAC -CTATCCGTTGCGCGCCGGATACCTGCACGAGGATGGAA TGA7CTTCTCCCCCGACGGTCGGTC"-CCGGGCCTTCGACGCCCAGGCGGCCGGCACGGTCTGCG GCAAC GGTCTGGGCATGG-'TGGTGC7-,G7ALCAGCTCGACGCGGCGCTGGCCGACGGCGATGCCA WO 00/22139 PCT/US99/23535 71 TCCACGCTGTGATTAAGGGCATCGCGGCCAACAACGACGGCGCGGCCAAGATCGGCTACACGG CGCCCTCGCAGAACGGTCAGGCGCGGGTGATCCGCGCCGCCCATAGGCTCGCCCAAGTCGCGC CGGAGACCATCGGCTATGTAGAAGCCCACGGTTCGGGCACGCCGCTGGGCGATCCGATCGAGG TGGCGGGCCTGACCGAGGCCTTTGACAGCCCGCGTCGCGGCTTCTGCGCCTTGGGTTCGGTCA AGTCGAATGTGGGTCATTTGGATGCGGCAGCGGGCATCGCGGGTTTCATCAAGGCGGTGCTCT CGCTGTCCCATCGGACCCTGTTCGCCAGCCTCCACGTCGACACGCCCAACCCGCAGATCCCGT TCGCCGACGGTCCGTTCCAGGTCAACACGGAGACCCGGCCCTGGCCAGCTGCCGACCATCCCC GCCGCGCCGGCGTCAGCTCCTTCGGCATCGGCGGCACCAACGTGCACGCCGTCCTGGAAGAGG CGCCGCAGTTGGCCGAGCACGCGGGGCGGCGGCGCGAGCGGCAGCTGTTCCTGGTCTCGGCGC ) GGACTGCAGCCGATCTGGAGCGACGCACCGCGGCGCTGGTCCGCCACCTGGCCGCGCATCCGG ACCTCGCACCAGATGACGTTGCCTTTACCTTGCACGCGGGCCGCAAACCGATGACCCACCGTC GTTTCCTGGTCGCCGCCGACCTCGCGGAAGCCGCCGCGCGTCTGGCCGAGCCCGATCCAGTCA AATCCGCCGCGGCGCGCGCCGACCGCTGCCAGGTCTGGATGTTCGCCGGTCTCGGCTCTCAAT ACCCCGGCATGTGTGGCGGCCTCTATCGCACCGAGCCGGCCTTTCGCGAGCAAGTCGACCGCT GTTTCGACCTCCTCGCGCCGCGTTGCGATTTGAAGCCCTCGCTCTTCCCCGAGCCCGATCAGG CCATCGACGCATCAGCCCTCGCGGCCATCGACACCGCCCAGATCGCCGTCTTCGTCTGCGAAT ACGCGCTCGCACGGATGCTGGAAGGCTGGGGGCTGCGTCCGGATCGGCTGATCGGTTACAGTT TCGGCGAATACGTGGCCGCCTGCCTGGCCGGCGTCTTCTCCCTGCCCGACGCCTTGGCAATCG TCCGCGAGCGTGGCCGGATCCTGGCGGCGGCCGAGCCGGGCGCGATGGTCAGCGTGCCCCTTC CGGCCGAGCGCGTCGCGTCGCTGCTGGAGCCGCCGCTTGCCTTGGCCATTGACAACGGCCCCT CATGCGTGGTGTCCGGGCCGGTCGAACCGGTGCGCACCTTCACCGCTCGCATGAAGCGGGACC GGGTCTGGGTGACGCCGCTCCAGGCCGAGCGCCCGATGCATTCGCCGCTGATGGCCGAGGCCG GCGGCTCACTGCGCGCCATGTTGGCCGGGTTCCGCCTGAATGCGCCGCGAATCCCGATCTTAA GCAATGTTACAGGAACCTACCTAACCGACGAGCAGGCCCGAGACCCCGATTACTGGGCCCGTC ACCTGTGCGGCAACGTTCGCTTCGCCGACGGTGTGCGAACCTTGTTGGCCGAGCGCGATCCGG TGTTCCTTGAATTCGGGCCGGGCCGCGATCTGAGCTCCTTGGTGCGCCACCAGATGCCGGAAG GCGCCGACGAGCCGATCGCACTGATCCGTCATCGCGAAGATCCGGTGCGCGACGAAGACCTCC TGCTCGATGGCTTGGGCCGCTGCTTCCTGCGTGGGGCGACCCTCCACGGGCAGGCCTTGTACG CCGGCCGAGGCTGCCGCCGCGTGCCGCTGCCCGGTTACCCGTTCCAGGGTCCACGCTGCATGC CGGC-CCGCGCCGGACTGCCCGGCCTGGCGCGACCGACCGTGGGAGCGACCACCATCAGCTACC WO 00/22139 PCT/US99/23535 72 GACCAGCCTGGAAGCGGGCGCCGCGC'TTGGCGGCTGTCGAATCGCTCGCGCCGCAATCCTGGT TGGTATTCAGCGACGGCAGCGAATTGGCGGGCGAGCTGGTGGCCGGCCTGCGCGCTTCCGGTT GCGCGACCACCCTCGTCGAAGGTGGGr'CTGGCGTTCGCGCGCTTCGCGGGCGGCTTCCGCGCGA ATCCCCGCGAGGAACAAGATCTCGC ACAGCTGTTCGCGACCCTGTCGGCCGAAGCGATGCTGC CCACCCACATCCTGCACCTGCTCAG :CCTGCCGTCGCCGGAGCGCGACTCGCCGCTGGCGCGCC TGGAGCACCTCACCGAGCTGGGCT7TCCACCATCTGCTGGCCCTGGCCCGCCAACTGGAGGCGG TCGGCGCCCCCGAGGTCCGCCTCGCCr GTGGTGACAACCGGCCTGGCGGCGATTGGCGGCGAGT CCGAGCTGCGGCCCGAGGTCGGGCTGr'TTGCGGGGACCTGTCCGCGTGATTCCCTTTGAJATTCC CGAACTTGCGGCTGCGCCTGATCGACCTCGACTCGGCCGATCCCATCTGGCGTAGCGGTTGTG AGCCGTTGCTGCGCGATGGGCGC TGCCCCGGGACCTGAGAATGCGCGTGCGCGGCACCA GCCGTTGGGAGTTGGGCTACGAGC CG,-GTCGAGGGGGGCACCGTGAGCACCATCTCCTCGCGAC TGCGCGAGGGCGGCGTCTATCTGA7TCACCGGTGGCCTCGGCGGCCTGGGTCTGGCCTTGGCCC GTCACCTCGCCCGGAAGTACCGCGCCACCCTGATCCTCGCTGGCCGGCGAGGCGCGCCGGCGC GCGAGCTCTGGCACCAGGCGCCAGC GGAGTTCGTACCGGTCGCAGCTGCGATCGCACAGATGG AGGAGTGTGGCGCCCGCGTGATTCCCGTCGCGCTCGACGTCACCGACGCCGACCAAGTGAACG CGTTGTTCGCCACCATAGAAGCTACr-GGTCGGCAAGATTGAGGCGTTTTCCACATGGCTGGCA TCGTTGACGGCGGCATCATTCGAACG1-CGCACGCGCGCTGCCAGCGACGCCGTGCTGGCGCCCA AAACGGTCGGAACCTGGATTCTCGATCGGGCTCTCCGCGGCGCCGGTGGCCGCTTCCTGGTGC TGTACTCCTCGATCAACGCGGTCGTCGCGCCCTTCGGCCAGGTTGCCTACGCCGCCGCCAACG CCTTCCTCGACGCCTTCGCCAGCGC-CCACGAACACGACGAGCGTCTTTTCCGCGTCAGCATCG GTTGGGACACCTGGCGCGAGGCCGGC-ATGGCCGTCGATGCCGCCCGCGCCCGCGGCGACCAGG CCCCGCTCGAAGGGCTTAGCGACGAGCAGGGCTTGCGCCTGCTCGAJAACCGCCTTGGTCGGTT GCGAACCGCGACTCCTCGTCTCCATLCAGCGAACTGCGCGCTCGACTAGCCGAGCATCATCGCA ACGGCGGCATTCCCCGGTTGCTCGG7GCCCCGCGCCAACGAGGCGGGTGCAGCTGATTCCGGCG AGGAGGGCGCCACGCAAGACGCGTCG-CCGGCCCGTCGCGC CCGTCCCGATCTGGTCGTGGCCT TCGCGCCGGCCGGCAACGAGCTGGAGCGCCGGATCGTGGCCATCATCGGCGCCTACCTGCGGC TCGGTCAGGTGGGCGTCGACGACAAC-TTCACGATTTGGGCGCCACCTCGCTCGACCTCATCC AGATCGCCCAACGCCTCGGTCGCGAC'-TTGGGCCGCGATGTCCCTGTCGTCTCGCTCTACCAAC ACCGCACCGTACGCGGGCTGAGCCS CTTCCTCGGCGGCGCGCTCCAATCCGCGCGGTCCGGCG TCCCGACGGGCGCTGCCGCACCGGGC"- -GCCGCCACGCCGGGGGTTGCCACCCCGCCGCGGCCAC WO 00/22 139 PCT/US99/23535 73 AACTGGCGACGAAAGCTATGGAAAGGGCTCCT ATGAGTGAAGTATCCATTCGCCCCG-GCTTGGACATCGCGGTCATCGGCATGGCCTGCCGCTTT CCCGGTGCCCGCAACCTCGCCGAC: 7ATTGGGCCAACCTGATCGAGGCCTCGAAAkCGCTCAGC TTCTTCAGCGAAGAGGAGCTGCGCAGGCCGGCTGCGATCCGGTCCACTGGCCCAGCACAAC 5TACGTGCGCACCAAGGGCCTGCT CCTGACGCAGACCGTTTCGACGCCGATTTTTTTGGTTAT TCCCCGCGCGAAGCCCAGGTGATGG-ACCCCCAGATCCGCGTCTTCCACGAGGTCTGTTGGCAG GCGCTGGAGCACGCGGGCTACAAC CC-GCATCGCCACACCGGCACGATCGGCCTGTTCGCCGGC GCCGCGCCCAACGTTTTTTGGGAG:-TTCTCTCCTATCGGTCCGATCCGCCATTTAGGCAAC TTAGTGCTCCAAC AlaACACGGTGGACCTCATCA DCTGACAGGGCCCAGCTACACCCTG:T- CACCGCCTGCTCGACCTCGATGGTCGCCATCCACCAG GCCGTCCAGGCGCTGCTCAACGG\C &AATGCGACCTGTGCATGGCCGGCTCGGTCTCCATTACG CTGCCACTGGTTGCCGGCTACACC7ACACGCCGGGCATGATCGTCTCGCCCGACGGCCATTGC CGCACCTTCGACGCAGGCGCCAA-TGG-CACTGTCTACGGCGACGGGGCCGGCGTGGTCGTTCTC AAGCGGGCCGAGGATGCGTTGGCCG ACGGCGACCACATATTTGCGCTCATCAAGGGCTCGGCG DCTCAACAACGATGGCAGTCGCAAG"AC--CGGCTACACCGCGCCCAGCGTGCAGGGGCAGGTGGAG GTGATCCGCGCGGCGATGAACCTG2C,-GGAGGTCGAGCCGGAGGCGATCAGCTACGTGGAAJACC CACGGGACGGGCACCACc3GTGGGC -3ATCCGCTGGAGTTCGAGGCGCTAAAGGAGGCCTTCGGA GGTGGCTGCAAGGCCTTCTGTGGAT--7GGGTTCGGTCAAGCCGACATCGGCCATCTGGACGTG ACGTCGGGGATCGCGAGCTTCATCA-'7 AGCTGGTCCTGGCGCTGGAGCACCGCATCCTACCGCCC D CCCATCACGCA---GAGTGTTGCAACCTCAACT GCTGAGCGCGAACCCTGGCGCGA~J-GATCTGCTGCCGCGTCGGGCCGGTGTCACCGTTCGGT CTGGGTGGCACCAACGTCCACATGA'-TTTTGGAGGAGTTTCAGCGCGAACCGGCGGCGAACAGC GCGCGCACGCGCCACCTGACGGTGCTGACGGCGCGGTCGCCGCAAGCCCTGGCGCAGCTGGCG GCCAACCTCGCCGAACACCTGCGCG- ACACCCCGAGTTGGCGCTGGCCGATGTGGCCCATACG CTGCTGCACGGCCGCAAGCCACA -'"CATTCGCGCGCATCCTGGTGGCGACCGATACGACGGCG GCGATCGACGCCTTGATGAACGAC CSCGATCCGCGAACGCGTTTCTTCGAAGCGACCGGGCGC GGCGAGTCGGTGATCCTGTGTTT-ACGAACGCCGCCGGAGCCGCGAGCGCCCGCTACCTC TGGGATCACGAGCCGCTTTATCGC -CGGCGGCGACGTCGTGCTTGGCTGGTGAGGTCGCCGAC CCGGATCTGGAAGGCTGCTTTAC---CC-CTGATCGCCGAGCAGGGCGCGGCAGCCGCCTTTTGC CACCAATACGCGCTGGCCGGATG2-:-TGCTGGCCATGGGGTTGACCCCGTCGGCGTTGATCGGC WO 00/22139 PCT/US99/23535 74 GTGGGCCAGGGCGAGTGGGTAGCAGCGGCGCTCGCGGAGGTGTTCCCGCCATCGGCCTGCTTG CGCTGGATTAGGTTCGGCGAACGGCTCCCGCAGCCGCGCGATCAACGGATTCCGTTTCTCTCC AATTTCTCTGGAAACTGGATCGTTGGGCGTGAGTTGGCCGACCCGGATTACCCCAGAAAGCAG AAGGGTAAGCGCTGCATGAAGCGCCGTCGGTCCCAACCTCGGTCAGCTGGTGCAGGATGGGGG CGATGGAACCGGCTCGGTCAGCTCGTCGCGCGCTGCTCTTCCGCGGGAAGCGGAGGCGGGACG GTGATCGGCCCGAGGGCGAGGTTCATCTCGTCGTCGACGAGCCGGGCGCGGGTGCGCGCCCAG TACCTGGGGGCGAGCTCGAGGTAGCGGTCCCGCGGCCAGTAGGGCATCGCGCGAATGACGTCG GCCAGGTAGGCCTCCGGGTCGAGCCCGTGCAGCTTGCAGCTCGCCACGAGCGAGAAGAGGTTG GCCGCGGCGGAGGCGTGGTCGTCGCTGCCGAAGAAGAGCCAGGACTTTCTCGCAACCGCAATG GATCGCAGCGCTCGCTCGCTGGCGTTGTTCTCCAGGCGCAGCCGACCGTCGTCGAGGAAGCGC CGCAACGGCTGCTCTTGGTTGAGGGCGTAGCCGAGCGCGGTGGAGACCAGGCCGCGCTCGCGG GGACGAGCGTGCTCGGCCCTGGCCCAGGCAAAGAACGCGTCGACCAGAGGGCGGACGACGACA TCGCGACGCACCTTGCGCTGCGCGGGCGGCAGGTCCGCCAGCGCGCGATCGGCGGCAAAGAGG GCGTTGATGCGCCGCAGCCCCTCGACACCGAGCTCGTGCTTGCAGACCGCCGCCTCCCAGAAG TTGGTACGGCAATGCGACCAGCATCCGACTTCGGTCGGGGGCGGACCGCGCTTCTCGTCGGCA GCAGCGCCTCTTGGTGGTGTGCCGCGGAAGAGGGCGTCATAGATGGCGTGAGCGTCAGCTTGA ATATACCGAGAGAAGCCGCGGAACATCTCGCAGACCGCGGCGCTGGTATGCTTGGGCTGGTAC TCGAAGAAGACGTGATCCTTGTCCGCGAGGACGACGAAGAAGTGTCCCTTGCGGCACGGCCCG GGCTTCTTGTCCTTGCGCTCCTGGATGGGCCCAGGCTGGACGGAGACCCCGGTGGCGTCCGTG GACAGGCAGAAGGCGGTCTCGAAGGCCTCTTTGCGCGCGGCCTCGACGATGGCGCCCAGGGTC GCACCGACGTCTTCGGCGTAGCGGCACATCGTGCCGCGATCGAGCGACGCGCCCTGAAGCTCC AGCTGCTGCTCCAGTCGATAGAACGGGACGCCGAGCAGGTACTTGCTGGTGAGGATGTGCGCA ATCATCGACGGCGCGAGGAACGACCGCCGGAACAACTCCTTCGGAAGCGGCGTCGTGATGAAG ACCGTGCAGGTCTCGCCCTTCGGCGCCGGCGGCGGCGCGTCGAGCGAGGGCGCGTCGAGCGCT GTGGAGGAAGCGCTCGGCTCGCCGGCCGCTGCCGTGTCCTCCGGGCTGACGCTCGCAGCGGGC GTCGGCGTCGGGGCTTCTCTCGCGACGACCTGGAGCGGGGCCGCTTCCTCCTCGCCCGAACTG CTCGCATCCGTGACGGACCGCTCGGCCTTGTACACGACGCGTGCGAGCACGATGCGGCGCATT CCGCCGCGCTCGTAGCCGAGTCGCGAGGTCTCCTCGACCCCGATGCGCGTCGCCGTCGCATCG AGCTCGGGGCAGGAGAGCTCGATGCGGACGACGGGCAGGTCGGACTCGGACAGGTCGCGACGG CCCTTGCCGCCGGACCTTCGTTTCGGCCCCTTGGGGTCGTCGTGCTGCCGCTCGTCGCCTGTA WO 00/22139 PCT/US99/23535 75 TTGCGCTCGGCGGCGTCGAGTGCCTTCGCGAGGCGCTGGACCTCGAGGACATCGAGTCGAAC GCCAGCTGCTCCGCGCTCACCTCGGCGCGCTCCGCCTTGGCCACGAACAGTCGACGTCGCAGA AGCTGCAGCTGCTCGAGCGCACGGGTGTAGGCGCGCCGAAGCTGCGCGAGCGCATCGCGCGCT CCCACGAGCTCGCTCTTTGCCGCGGCGAGCTCCGCTTCGAGCTGCGCGATGCGCTGCTGCTCG 5GCCGAGAGCGTCGGCTTGGCGGCGGCGTCGTGCACGACGCCGCTCTACGTAAGCCGCGCGTAC TTGTCGAGCGAATTCGTGCGGCTCAGTGGACGCGGCGCGGTGCGCGCCTTCGCGGTTTGGACG TGGGCGCGATCTCGATGCCGTCGAGCAGCGTCTCGAGCGTGGCGTCGTCCACCTCGACGTGCG TGGCGCCCTCGGTCGGGGGGTCGGGAAGTGCGIAACGCTCCGCGATCAAGGCGTTTTGAAAACA GGCAGATTCCACTGCCATCGAGAGAGATCTTGATCGTGGTCCGCCGCTTGCCGACGAACG 0CGAACAGCGCTCCGCAGCGAGCCTCGTACCCCACACCTCACGGATGAGACCCGAGCCGCT CGAAGCCGTAGCGCATGTCCACCGGCTCCAGCGCGACGAACACCTGCACGCCCGCCGGAATCA TCGCCCCGCTCCGCCGAGGGCACGGACCACCTCCGCCAGCAGCGCGGGGTCGAJACCCCGCGGC GACGCGCACCCGCGCGCCGCCGACCTCGACGACGAGCTCCGCAGCGCTGCTCGTCACGGCGGG CGCCTTCGGCACCAGGCGCAGAAAGCGCGGTGGCTCGGCCCGCGACAGCCGGCTCGACCAGCC DGTGCAGCGTCGAGGCCGCAJ&ATCCGC GGCTCCGAGCGAACTCCTCCGCCGTTTCACCACTCTC GCGCCACGCCCGAACGCGCTCGGACCACATCACTTCGGTCGCCTTCGTCCTTGTCATGCACGC CATCATGAACTGGACAGCGCAGCCGGGGTGAGACGGCGCTTCGCGCAGCGCTTACGCAGAJAGG CGCGCCGCGCGCCATTGTCGGATGCGGTGCGCGACTTCGCCGCCGATCGGCTGTTGCTGGAAC TGGGACAACCACTGGACGTAACGGCTGAGCGAGCCACGGCTCCAGCTCGCGCGGGGCGACC TGTTCGGCGCCTACCAAGCGTTGGCCCAGCTCTGGATCTGCGGCGCCCTGGCCGAACCGCCGC GACTGTATCCCGACGAACACCGCCGGCGCGTGCCGCTGCCGAGCTACCCCTTCGAGGGAA]kGC GGTTCTGGATCGAGGGCTCGCCGTTCGA]ACCGCGCCCGCCGCCGGCGCCTCACCCCAJACCCG CCGATTCGGGGGACATTCTCAGGGCGACCCGGCGGACTGGTACTATCGGCCGCGTTTCGAJAG CGGCGCCGCTCTTGCCCAGCCCGTTCGAGAGCGAACCCGGCGATTGGCTGGTGTTCGAAGATG AGCTGGGGCTCGGCGCCTGGCTGAGCGAGACCTTGCGCGACAAGGGCGCGCGGGTCGCGACAG TCGTTCGAGGCACCGAGTTCCGACGCCTGGCGTCACAGCGCTTCCAGCTTCGTCCCGATCGAC GGGAC-GATTACCGGACCCTGCTGCACGAGTTGAAGGCGCAGGGCATCGCGCCGGTCCACCTGT GCCAC -CTATGGAGCGTGACCGCCGCACCGGATGCCGAGCAGTTGCTCGACGTCAGCTTTCACA GCCTGGTCCATTTGGCGGCCGCTTTGGGTTCGGTTGGCTACTTCCACGCCATGAAGTTGAACG TGGTCGCCAACCGGCTATTCGACCCCGAGTCGCCCGAGCGCACCGAGCCCGCCAAGAGTCTGT WO 00/22139 PCT/US99/23535 76 TGCTCGCGGTGACCAAAGTCCTGC CGCAAGAGGTGCCCAIXCGTTCGAACCCGCGCCATCAGCG TGGACCTGGATCGCTCGTTCGACGCG- GCGGCGCCCGCCTGGGCCGCCAGTTTGTTGGTTGAJAT GCGGCGCGCCCGTCGAGGAAACGG7TGGTGACCTACCATGGCGCAGCCCGATGGCTGCGCCGCT TCGATCGCGTTGCGGTGAATGGTCTC -GGCCCGTTCCACCCCGATCAACCTGCGCCGCTGCTGC 5GCGAGCGCGGCGTGTACCTGATCACC -GGCGGCCTGGGCGGCGTGGCTGGCCAGTTGGCGCGCT ACCTGGCGCGGGCCTGCCGGGCGCGG7TTGGTGCTCACCGCGCGCCGGCCCCTGCCCGAGCGCG ACCAGTGGGATCGGGAGTCGGCCGG-CTGTCATGGGACGACAGACGCGCCAGCGCATCGAGC TGGTGCGCGAGCTGGAGCGGCTGG31-GCCGAAGTATTGGTGGTGGCTGCCGATGTCGCCGACG AAGCGGCCATGGCGCAGGCGATCGAG ,GCCTCACTGGCGCGATTCGACGCTTTGGACGGCTTGA 0TCCACGGCGCCGGGATCGTGCGGGT-CGr'CGTCGGGCCGCACGCCGATCGGGAGTATGACGCGGG CCATGTGCGAGGAGCAGCTCCGCCC CAAGATGTTGGGCCTCGACGTCGTCGACCGCCTCCTGC GCGATCGCCGGTTGGACTTCCGCArnTGCCATCTCGTCGCTCGCCCCGATTCTCGGCGGCCTCG GCCACGTCGCCTACGCCGCCGCCAM''CCTCTACATGGACGCGTTCGCGACGCGCGCCGCCGCCG GCAACGCGCCTTGGATCGCGCTGA-C-CTGGCCGATGGGAATACGAcocCCCGGCTACCTACG DACGAGCGGGTGGGCCGTTCGCTCA-T-GCAGCTCGAGCTCACCAACGAGGAGGGTATCCGCGTCT TCCAGACGGTGTTGGCCTTGGCCGCG'-CGCGGCCCGCTACAGCAGATCATTATTTCCACCGGCG ACCTCCAGGCCCGCCTCGACAAATGG -:ATTCACATCAATCCCTGCATCGCCGACCGGGGCCGG TCCAGCTCAGTCGCCGGACCGCGGC-ACCCCAGGGCGGTTTCGGCTCGGAGCGCGCCGCCTTCG AGCGCTGTAGCG~-l-ATTTCGGTAGGTGCCACA DACTTCTTCGATCTGGGCGCCAGCTCC3CTCGACTTCATCCACCTCGTCAGTCGCTTCAGCAAGG CCATCGAACAGCATGTACCGCTCGAG-GCCCTGCTCGA.CACTCCACCCTGCACGACCTCGCCG CCCACCTCGCGGGCGACGCGAACACCGACGCCAGCGACGAGCGCGCATTCGCCAACGGCTGC AAGGCGCCAAGTCCGGCGACATCGCCr-ATCATCGGCATGGCCGGCCGCTTCCCGCTCGCGCCCG ACCTGGACACCTATTGGCGCAACC7GGTCGGAGGCATCGACGCGGTCAGCTTCTTCAGCGCCG DAGGAGTTGCGTGCTGCTGGCGTCACCGCGGCCGAGATCCACCACACCAACTACGTGCCGGCCA AGGGGCGCTGCGCCGACCAGGACTT3-TTCGATGCGGCCTTCTTCGAATACACTGCCAGCGACG CCGAGCTGATGGACCCGCAAAATC -CGTGTTACACGAGGTCGTGTGGCACGCGCTGGAAGACG CCTGTTTCGACTTCAACGGCGATCAO-GGCCAGGTCGGCCTGTTCGCGGGCGCCTCGCCGAACC TGTGGTGGCAGTTCGTGGCCAGCT----TCCGAGGCCGCCAAGACGCAGGGCATGTTCACCACCA CCCTGCTCAACGACAAGGACTCGA:--GCGACCCAGATTTCATACAGCTCGGTCTAAAGGGCC WO 00/22139 PCTIUS99/23535 77 CCGCGGTCACCTTGTTCACCGGCT -TCCACCTCGCTGGTAGCCGTTGACGCCGCCTGCCGCT CGATCTGGTCCGGTCAATCGGACATGCGCCGTGGCCGGCGCGGTCTCGCTGACTCTCCCCGATA AGGCCGGCTACATCTACGAAJGGG CATGCTCTTCTCGGCCGACGGCCATTGCCGGGCTTTCG ACGCCAACGCCACCGGCATGGTCT- CGGCGACGGCGCCGGCGCGATCGTGCTCAAGCCGTTGG ACGCGGCCCTGCGCGACGGCGACCC"-ATCCATGCGGTGATCAGGGCTGCGCCACCACACG ACGGCGACCGCAAAGCCGGCTACAC CAGCCTCAGCGCCCAAGGCCAGGCCGAGGTGATCCGCT CGGCC CAGATCCTGGCCGACGTGGC -zCCCGAATCCATCAGCTACGTGGAAGCCCACGGTACCG GCACCAGTTGGGCGACTCGATCG;3 -ATCAGGCGTTGIAGCPAkGCCTTCGCCAGCGACAAGA ACGGATTTTGCGGCATCGGGTCGG- -- AAGACCAACCTCGGTCACCTGATGGCGGCGGCGGGGA TGGCC-GGCCTGATCAAGACGGTTC--ZGCGATGAIAGCACCGCCAATTGCCG-'CCATCGCTGCACT GCGACGAAGTGAACCCCGACCTGG2 -ZTTGGAGCGCAGTCCGTTCTACATCAACACCCGCCTGC GCGACTGGGTTGCACCGGGCGGGCC 3-CTGCGGGCCGGCGTGAGTTCGTTCGGGATCGGCGGAJA CCAACGCTCACGTCATCCTGGAGGA'--CCGCCGACGCGCGAGAGCGGCACGCGCATGCGCCACT GGAAATTATTGATGCTGTCGGCGCC CAGCGAGGCGGCGCTCGACCGCCAGGCCGATAACCTGG CCGAC-TACCTGGAGCGCCATCCCGZ ,-GCCCACCTCAGCGACGTGGCCTATTCCCTCCAGACCG GCCGGCGCGTTCTGGCCTGGCGGCG CACGGTCCTATGCGAGTACCGCGAGGACGCGGTGACCA GTC'G-CGCGAGCCACAGGCCAAGC_ 3CGTCCAGACAAGTCGCGTCCGCTGGGACCACAAGGACG TGG"-CTTCATGTTTCCCCGTCAGGC CGCCCAGTACCTCAACATGGGCCGCGACTTATACGTCA TGGAG-CCGGTCTTCCGCGAGGTCA- 3GACCGCTGCTTCGAGTTGCTGGCCCCTTTGTGGTCCG AGCAT-CCGCGCCAGATCCTTTATC C CGAGGGCCGGGTGTCGACCCTGCTCCACCGGACTGATT ACACCCAGCCGATCGTGT'rCTGCT -CGAGTACGCCCTCGCCCATTTGCTGCTCTCCTGGGGAT TGAAGCCGGCCGCGACCATCGGCT-AGCTTCGGCGAGTACGTTTCTGCCTGCCTCGCCGGCG TCTTC7-TCCCTGGAAGATGCGATCC'-mCTGGTGACCGAGCGCGGTCGGCTGATGGCGGCTTTGC CCGCG-GGCGCCATGCTCAGCGTCC C GTTCCCGAATGCGAGCTGCTGCGGCTGCTGGACGGCT TCCACGCCCAATCGGCGGCCCATC--GCGCTGGCCGTCGACATGGCGCCTCCTGCATTGTGG CCGGC-GAGCAGGCCGCCATCTCGGC C-TTCGAATCGATGCTTCGCAAGAAGCGTCTGTTGACCA TGCC-CGTCGCGGTCAGCCACGCCC CCC -ATTCGCAGGTCATGACCGGCGCGACCGACGCCCTC GCACC -ATCCTGCGGAAGATCCCcC ---TCCCCGCCGACAATTCCCTTCATTTCCTGCGTCACCG GCAC CTGGATCACTGCACAGCAGG C :--ACGGATCGCGAGTATTGGGTGAACCACATGTGCGGGA pCGGCGC-GGTTCGCGGCGGGTCTGACC:-GAGCTGGGTCAAAACCGCGAGGCGGTGTTCCTGGAAG WO 00/22139 PCT/US99/23535 78 TAGGTCCGGGCCGCGACTTGACGTTGCTGGCCCACCGCATCCTGGCCGACAGCGCGGCCGTGT TCGAGCTGGTCAAGGCGCCCGACGGCGGCGACGACGATGGGTTCCTCCTGCTGGATCGATTGG CCAAGCTCTGGAGGCTGGGGATTTCGATTGACTGGGCCGGCTTCTACGCGGATGAGCGGCGGC GGAAACTCTCGCTGCCGGGATATCCGTTCGAGCGGCGGCGCTTCTGGATCGAGGGCAACCCGC 5TGGAGATCGCCGCCGGCAGGCCCAATGTCCAGGGGCCGCTGGTCAAGGCGTCGGACATCGGCG CTTGGTTCTACGTGCCGCAATGGCGGCGGTCGGTGCTCGCCGAGCCGGGTACAACGGCGGCGG GCGCCGCCGTCACGGCGG--AGCAGGCACGCGTCGTGACCGAGCTACGGGCGGGATGCGCGTCGG CCGGCTTGGGCAGCGGGGCCTGCGGACTGATGGCGTGCCCCGTCCGAGCGTCCGGA GTGTAGCGCCAGCCGGGCTCGACCAGCGCAGCGGCGCAGACCGGCGCGGACTGCCCGACACCGA DCTGGGGAGCCAGCGGCTGTGCCAAAGGACGGGGCCGAGCCGCGGCCGACCTGGCTTATTTTCG CCGACGCCGGCGGATTGGCCGATCTTTCGCCAAGCGGGTTCAGGCCCGCGGCGAGAAGCTTT ACCTGGTGGCTTCCGGCTCGCGCTTCGAGCGCCTGGCCGAGACCCGCTTCCGCCTCGATCCCG GGGCCAAGTCCGATCACCGCCTGCTTTTCAAGGCGCTCGACGAGGCCGACATCCTGCCGACCC ACCTCCTCGACTTCCGCTCGCTTGACTGCGGCGGGCCCGACGCCGACCCCATGGACCAGGCCG GCTTCTTCGGGCTGTTGCACCTGGTCCAGGCGATGGCAGAGGCCGGCTACAGCCATCCCATTC GGCTGCTGATCGTCAGTTGCGGCGTCTACGATGTCACCGGTGCCGAACCGCTGCAGCCGGCGC GGGCCACGATGATCGGACCGGCTCTGTGCATCCCGCACAGTATCCGCACCTCGAAAkCGAGCC ATGTGGATTTGGGCGTGGTCCATGCCGACGAGCTCCACGCCGCGCGCCAGCTCGACAGCCTAC TTGCCGAATGCCTAAGTGCAACGGCCGAGCGCCAATTGGCGCTGCGCGGCCGACACCGCTGGC TGCTGGACTACGAGCCAGTLCCGCTTGCCGCCGCTCGACCCGGGCCGTCTGCCCTGGCGCCAGC GCGGGGTCTACTTGATCACCGGCGGTTTGGGCGGGATCGGCCGCATCCTGGCCGAACACCTGG CCCGCACGACCTCGGCTCGCCTGGTCCTAJATCGGCCGCGAACCCTGCCCGACCGCGACGACT GGAGCGCGACCCCACGCAGCCCCACGTCGAAG TCCGCGCGATTCGCGATCTGGAAGCG 'CTAGGCGCCGALGTCCTGGTCCTCGCCGCCGACGTCG CCAGACGCTCCAGCAGTCCCGACCCTGCCLTCC GGGTGATTCACGGCGCCGGCCTGATGGACGCGCAGCTTCTCACTGATCGACGCCCTCGACC ACGACCTCTGCGCCCGCCAGTTCGAAGCAAAAATCCGCGGCGTCTGCGTGCTCGACCGCGTTC TGG-CCGACCGCACGCTCGACTTCTGTCTGCTGATGTCTTCCATCTCCACCGTGCTCGGCGGCC TGGGC' -TATTTCGGTTACGC -CGCGG 'CCACGCCTTCCTCGACGCCTTCGCCCAGGCGCGCAGCCC GC-GACGCCGCTTTCCCCTGGCTTACCGTGGCCTGGAGCGATTGGAAGTACTGGACCGAGCGCA WO 00/22139 PCTIUS99/23535 79 AGATGGACAACGAGGTCGGCGCCGTC-ATCGACAGCCTCTCGATGGAACCCGCCGAGGGCTTCG AGCCGTCACCCGCGTCTTGGCTTGGGGCAGGCGCCCCACATCGCCAACTCGCCCGGTGACC TCGGTCGCCGCCGGGATCAATGGGTCAACTGGCCAGCCTGAATCGGCGCACTCCAGCGAGC CCGAGCCGGCTAGGCATGGACGTCCGGCGCTCTCCAGCGAJATGGGTCGCGCCGCGCAJACGTGG TCGAAGAGAAGCTGGTCGCCATTTT CGAGCAGGTGTTCGGCACTGCGGCACTGGGCATCGAGG ACAACTTCTTTGAGTTGCGCGGCGACTCGCTCAGGCGGTCATGACCGCGGCCCGTATTCA AGGAGCTGAACGTGGAAGTGCCGCT GCCGACCTTCTTCCAGATGCCCACGGTCGCTGGCCTGG CCCAGTTCGTGACGCAAGCCAAGCGC AGCGGCCGGGAGACGATTCGGCGCACCGCGCCGCGCC CACATTACCCGCTCTCGGCTGCCCAGGGCCGCCATTACCTGCACTACCGCATGGACCCGCGTT GTACCGCATACAACGATCCCTTCG'CCACCTGATCGAGGGTCCGCTGGACGTGGATCGCGTGG AGCGCATCCTGCACACCCTCATCC:-ACGCCACGACTGCTTCCGCAC-CTCGTTCCACTTCCGCG AGGGCGAGCCGGTCCAGGTGATTCACGATCGGGTGGACTTCAACCTGGCGCGGATTACCTGCG CGCCCGAGGATTTGCCCGAACGGATGCGCGATTTCATCCGCTCCTTCGATCTGGACCGACCGC CCGCCATGCGCGCCGGCCTCTTCGTCACGGGGCCCGAGCGCCACGTGCTGCTAAJTCGATTTTC ACCACATTATCACCGATGGCGTGTCGTTCGAGAACTTCGTCGGCGAGTTCGCGGCGCTCTACC GCGGGTCGCGGTGATGGAAGATCCGGGCGAGG ACCGGGGCCGCCGCGCCAACAGCGAC-CAGGC-CCGCTACTGGACCGAGCAGTTGGCCAATGCGC CCGGGCCGATCGAGCTAACCACCGATTTCCCCCGTCCCAGTCGACGCAGCTTCCGCGGCGACC GCGTGCGGACCGTGCTTGATGCGGAGCTCGTTGCTCGACTCAGAGCACGCGGCGCGCCTCG GCATCACCCTCTATAGCCTGCTGCTGGGCGGATTCTCGTTATTGCAGCACAAGCTCTCCGACT CGCACGACATCGTCATCGGTTCGCCC 'GTCGCGGGCCGCACCCGGAG-CGAACTCCAGGATCTGC TGGGCGCGTTCGTCAACACCCTGCCGATGCGCCACCGCATCGACCCGACCCATACCGCACGGG TCTTCTTGGAGCAGGTCCACCAGACAACCTTGGCGGCCCTCAGCTACCAGGAGCACCCTTTTG ACGAAATGGTGGCGACGCTCGGGTTCGCCGCCGATCCGGCTCGCAACCCGATCTTCGACACGA TGTTCTTGCTGCAGAACATGGCCATGGGTGCAACCACCATTCCCGGTCTGCGGCTCTCGCCTC ACGACACTTTTCACCGCAAGGCATrnGTGCGACCTGATGCTACAGGCGACCGAGTATGACTGCC ACCTGGAGCTGGTGCTCGAGTTCGCCACCGACCTGTTCCGGCTGGACCGCGCAAGTCTTGC TCGACCGCTACCGCCAAGTCTTGGAGTGGCTG'TTGGCGTACCCCCATGAATCGATAGACGATT TGCCCCGCATTGGATGATGCAGC''AGGGGCTGT TCTCAGATTTCGAACCCCGCAACG?-GACGAAAC CTATGGCGCGCCTGAGCCGCACAGATCTCCA WO 00/22139 PCT/US99/23535 80 ACTCGCCATTCACCAGCGCACCGT3 -- AGCGCGAA~TATTGGCGCGCTCTGTTCGAGCGCCATCC GCAACGGTCCAGTTTGCCGGGGGT'GCTCACCGCCCCGATCGGCGACGAGTCGACCCGCGAGAC CTTGTCATTCGTCCTCGACGAAGA7CCCCTTCGGCTGAGTAATCGTTCGCCGCAACGCCTGCT CACGGTGTTGGCGGCTGGCCTCGCGGC- -TTTCCTCCACCGCTGCGACGGCGCTGAGCGCTTCAC CCTGGGGTTGGCCCTACCGCGCCAAC:CCGATGACCATCACCCGATCCTCAACAGCTTGATCGC GCTGGGGGTCGCGGTCGACTCGAG--'CGACCTTCCGCGATCTGCTCTATGCGCTTCGATCCGA ATACCACGAGGCGATGCGCCACGC CAACTTTCCGCTGGCGACCTGGTGGCGCGGCCTACCCGG CGCAACGGCGCCGTTCGACGTCGC C TCAGCCTGGACCCCTTCACAGACGGCGATTCGCTGGA AGACCACGCGATCGGCGCGTTGTT C C-GGTTCGCATTGGAGGGTGAGCGCCTCACCTGCCGATT GCGATTCGACCCTGCGCGCTATGAG- TCCCGCGATCGAAACCTCGCCGATCGTTTCGCCCG CTTCCTCACGCGCCTGTGCCCGGAC -3CCTCCACCGTCATCCAGGCGCTGGACCTTTCGCTGCC AAGCGATGAATCGGTGTGGCGCGTC-AC'TGAJAGGCGTGCGGCGCGGCTATTCGCAAGACCTGAC GCTAGACCGCGCGTTCCGCCGCCAGG7CCGCGCAAACGCCCGATCAGCCGGCGATCACGTTGAA CGGGGACGTCCAGAGCTACGCCGAG'3TCGACCGCCGCAGCGACGCGCTGGCCCGCCACCTCCG TCGCCACGGCGTCGGTCCGGACATTGTGGCCGTCAACGCCCGGCGCGGGCCTAATCAGCT GACGGCCCTGCTCGCGGTCCATAA-GGCCGGCGGCGCCTACCTGCCGATCGATGCCGAGGAGCC GGCTGCCCGCCAGCAATTCAAGGTG7CGCGACAGCGGGGCGCGGTTGGCACTGGAGCCGTCGCC GGACCAGGCGCTGACCGTCACCGAC CTGCCGCGGCTCTTCCTGGACGATGCCTCGCTCTTCGC TGACGGCGGGCTCGATGTGCCGCGCGGCGCCGACTCGCTCAATCCGGCCTATGTGATGTACAC pGTCCGGCTCGACCGGACAGCCCAACG'-GTGTGGTGGTTCCCCACCGCGGCGTGGTCAATCGTTT GAATTGGGGGCAGTCCCGTTTCCC C CTGGACGAACGCGACCGAATCCTCCAAAAGACGCCGCT GCTGTTCGACGTGTCGGTCTACGAGCz TGTTCTGGGGCGCATGGACGGGCCACCCTGGACAT CCTCCAGCCCGGCGCCGAGCGCGACC'-CCGACGCAGTGGCCAGGGCCCTGGCCGAGCGCGCCAT TACCGTATGCCATTTCGTGCCTTCC-ATGCTGCTCGTCTACTTGGAAGTCATGCGGCGGCACCA TGCGCCGCCCGTGCCCGACCGCCTC C-GTTACGTCTTCGTCAGTGGCGAGGCCCTCGAJACCGGA CCACCTCGCCCGGGCTCCAGCAGAT--GGTCGGCGCCTCGGCCGCACGATTCCCCTCCTTAATCT CTATGGACCAACCGAGGCCTCGAT G AAGTCTCCTGCTTCGCCTCTCCCGCCGACCATGTGCC GCGCCGGATCCCCATCGGGCAGCCC2-ATCGCAACGTCGCACTGCACGTTCTCGACCGGCGCCG CCGTCGCCAGCCGCCCTATCTTCCTG-GCGAGCTGTTCCTGGCCGGCGACTGCCTGGCGCGCGG CTACCTCAACCGTCCCGACCTGAC -CGCCTCCACTTCGTGCCCAATCCCTTCGGCAACGGCGA WO 00/22139 PCT/US99/23535 81 GCGCATGTACCACAGCGG"'CGACTTGG7CGCTCGTGCGCGGCGACGGCCAAGTGGCGTTTCTCGG CCGCCGTGACCACCAAATCAATCTG'GTCGGTCGG]ACGCTGGGCGAAA\1TCGAGAGTCA TTTGCGCGGGCTCGAAGGCATCGCCGCCGCCGTCGTCCAGGCCGAGTCGCAGCACCATGAJAAC CCTGCTGCACGCCTACGTCGTCACCAACGACGCGGGCCTCAATGCGGCCCGGCTGCGCGCCGC CCTCGCTCAACATCTGCCCGAGTACATGATTCCCCAGCGCTTCTCGCGGCTGGCCGAGTTGCC GCTGCTGGCGGCAGGCAGATCGAC-r-GCGCCCCCTCGCGCACGTGCAAJCGCCGCTCGCCAG CGGCGCGCCCTTCGTGGAACCCAGC-GGGCCCACCCAGCAGCGTATCGCAGAACTGTGGCGCCA GGTCTTAGCGGTCGCCGAAGTCGGCG7CCGAGGATCCCTTCTTCAGCATCGGCGGCAACTCGCT CAATLGTGCTCAAGCTCAGCGCCGCC-CTGAGCGACGCCTTCGCGCGTGACATTCCCATGCCGGC CCTGTTCCAATACGACACCATCGCCGCCCAGGCCTCCTGGCTCGACGGGCAGGTTGACGAACG GGCCCAATCCGCCGCGCTCGACCGGCz-AGGCCGCCGAGGCGGCGCTGACCCTTCAAGAGACCGT GGCCATTTTTGAGGGATT CGATGAC -GAACCATGACCATCACc3AGGAGAGCAGCGGCCTGGAGA TCGCCGTCATCAGCATGGCCTGCCG :ATTCCCGGGTGCTGCCGATTGCGACGCATTCTGGGA ACCTGATCAACGGGACCTCCTCGATLCACCCATTTCAGCGACGACGAGCTGATCGCGGCCGGCG TTGACGCGCGCGACCTGACGCCGCAGTACGTGCGCGCGGCCGGCCAGATCGATGACGCCGAAC GGTTCGACGCGGCCTTCTTTGGGTAC TCCCAGCGTGAGGCCGAGCTGATGGACCCCCAGTTCC GCCTLGCTCCATGAATGCGCCTGGT C C-TGTCTGGAACAGGCCGGCATCGATCCGCGCGTCGAAG CCGC GCCGATCGGGCTGTATGCCGC-GCAGCCGACAACACCTACTGGACGCGCTCTCGTCGC TCA-GGCCGCATGACATCCGCACATTCACCATT TGTGC7 ACGCTGGTCGCCGCCGCGCTC -ACCTGAGGCCCCGCGGTGGTGGTTCAAGCGCCT GTTCGACCTCGCTGTTGGCGGTCCACTCGGCCTGTCGTGCGCTCCTGACCGGCGAATGCCGAG TGGC-CTTGGCCGGTGGGGTGGCGCTG%''CGCTTCCCACGCCCGAGCGGTTATCGCTACGAACCTG GCATGATCTTCTCGCCCGACGGGG7TGTGCCGGCCGTTCGACGCGGGCGCTAACGGGACGGTGC CC-CAGCCGGTGA- TGAGCCGACTCCCAGCGGC CGATCCACGCCGTGATTCGCGCGACC-GCGGCAACAACGATGGTGCCCGCAGACCGGGTTCA CCCCG.CCCAGCGCCCACGGCCAACC CGAAGTCATTCGCACGGCCCTGCGCCTCCCCCGGGTGC CGCC GAATCGATCGACTACGTCGA-GCCCCACGGAACCGGCACGCCGCTAGGCGACCCGATCG AGCT''-AGCCGGCTTGGTGGAGGCCT-:CGCCAGCGAGAGCGCGGCTATTGCCGGCTGGGCTCGG TCA,ATCCAACCTTGGTCATCTGGAC--ACTGCTGCCGGCATCGCCGGCCTGATCAAGACCGTGC TGCCC---CTCGAGCACGCGCACATcC -CC-AAGTCCTCCCACGTCGCCACGCCC.AACCCCGCGGCGC WO 00/22139 PCT/US99/23535 82 GCCTACACAAGACGCCTTTCCGCATTGCCGCCGACGGGATGGCCTGGCCGCGGCGTATGGCGA CGCCGCGGCGGGCGGCGGTGAGTTCGTTCGGCATCGGCGGCACCAACGTCCACGCGATTTTGG AGGAGGCGCCGCCCCGCGCGCCCGAGCTGGCGGACGGGCGCAGTCAGGTGTTCGTCTTCTCCG CCAAGGACGAGGCGGCGCTGGACCGTGCCCTTGCCAACTATGGTGCGGCCTTGGAGAAGCGCG GCGACCTCGCGGCGGGCGCGGTGGCCTGGACGCTCCAAAACGGCCGGGCCGCATTCGAATGGC GAGCCAGCGCGGTGGCATCCGACCTCGACGAATTGGCGGGCGCATTGCGCGGCGAGCGGCCCG GCGCCGTCAAGAAAAACCGAATGGCGCGCGAGGATAAGCCGGTGGCGTTCTTATGTTCGGGGC AGGGGAGCCAGTACCGTGGCATGGGCCACGACCTGTACCGCGAAGAGCCGCGTTTCCGGCACC ACCTCGACGCCTGCCTCGCCATCCTCGCCGAACACAAGCCCGAGATCGACTGGCTGGCGTTGC TGGGCTACCGCGACGAGGACGAGCCAACCGACCAGATCGGGACGTCCTCGCAGGGCCCGAGCC GGTCAGCCGCATCGAACCCAGCGGAGCTCCTCGACAGCACCGAATTCGCCCAACCTTTGCTTT TCTCCATGTCCTACGCGCTCGGTCGGCTGTGGCTCGACTGGGGCGTGCGACCCACGGCGATGA TCGGGCACAGCCTGGGCGAGTACAGTGCTGCATGTATTGCAGATTTCTATGCACTCGATCAGG TGCTGCCCTTCATTCTGACCCGCGGTCGAGTCATGGCGCAATTGCGGCGCGGCTCGATGTTGG CCGTCAGCGGTGACAGCGTTCTGATGCGCGAGCTGATCGCCGATGCGCTCGATTTGGCGGCGA TCAACGGCGCTGACCAATTTGTCTGGAGCGGGCCGAGCGAGGCTGTCCAAGCCGCGGGGGTCC GACTGCGCGGCGCCGGCCTGCGTGCCACCGAGCTGAACACCTCACACGCGTTCCATTCAGCCA TGATGGATCCCATTCTGGAGGAGCTAACGGTTGCCGGTTCGCGACTTCAGGTCGGTGTCGGGA CGATTCCGGTCGTTTCATGCGTTACCGGAACCTGGTTGACGGCGAAGCAGCTGGCCGATCCGC ) GCTACCACGCGCGTCACGCGCGCGAACCGGTGCGGTTCGCGGCGGGCCTAGCGACGCTGACAG GGGAGGAGCCGCCGCTGATGCTCGAAGTGGGGCCGGGCTCGACCCTGGCGGCTTTGGCCCGCG AGCATTCGAATGCCCGCCTCCCGGTCGTCACCAGCCTGCGCCACGCTCGCCAGGCGACGCCCG ATCGCCAATACCTGCTCGAAACGCTCGGCTGCCTTTGGCGACACGGGGTTTCCGTCGATTGGG GGGCCCATGCCGGACGTTCGCGACGCTTGGTTTCGCTGCCCGGCTATCCCTTTTCCGGCGCGG TGCGCCGCTTAGCCGGCGACCCCCTCCGCCTGCTGGCCGGAGCCCGCGCCGTCGCCGCCCCGT CGGGAACGCGCCAACTCAGCGCCGACGCGCGCGACCTCCCGAACACTCCGGAGCCGACATCCG GCGCCGTGTCGGCGATCAAAGCGCCAATCGCCGCCGCCGATCCCGGCCTCTATCGCCTCTCCT GGCGCCAGGCCGGAACGGCGCCGCTCGGTCCGCCCGATCTCGGTCCGCCCCGCGACTGGATCG TCTTCGCCTCTGATTCTCACCTGCTCCAGGCGCTCAGGGCCAATCTCGGGACGCGCGCTCAGC GGGTGACGCTGGTGACGCCGGGCCAGGAGTACGCAGCCGAGCCGTCCGGGTTTCGGCTGCGGC WO 00/22139 PCT/US99/23535 83 CGGACCAGATCGACGATTACCGCGCC -CTGTGGGCGGACTTGGCGCAAACCGGTATTGTGCCAC GATACATCGCGTTCCTCGCCCCGTT-CATGTACCGGGCGCGCATGGCGGGCGATGCCTCGACCC TGGACGAAGTGCGCGAGGGCGGCTTCCTGCCCCTGACCCGCTTGATCCAGACTCGCCCGCCAG GCGGACCGAGCGGACTTCTAAGCCTCACGATCGTCACCCCGGCCGCCCTGGCGCTGGGCGACG AAGCGACGCGCCCGGAAkTGGGCAATCCTGCACGGGATGGTCGCCGGCTTAAGCCGCGATTATC CCGAATGGCGCTTCGTCTCGATCGAC GGCGGCGACCCATCCCCGCATCGGTGCGAAGGTCTGG CCCGCTTGATCGCGCTTCATGCGGrnC-GACGAGGCTGGCCCGACCCGCTTGGCGCTGCGCGGCC TTCACGCTTGGGTTCCACAGTGCGAG:CACGTTCAGCCGGCCACCATCCCTGGGGCGGGTATGT GGCGCGAGGGTGGTGTGTACATGA7AACGGGCGGATTCGGCGGGATCGGTCTGGCGCTGGCCC GCGCCCTGGCTCGAGAAGCTCGCG~CAAGCTGATCCTGGTCGGCCGAA-CCTGCCCACCGCGC CGATCGATCTCGAGGCTTGGGACGCG-CCGCCGTTGATTCTCACCGCCGACGTCGCCGACGAAG AGGCCATGCGCCGCGTCTTCGATGCCr-GCGCACGCCCGGTTCGGCGCCATCGACGGCATTCTTC ACCGCGGCCGTGA(-TTCCACATGAGGCTCAGC TGCTGCACGCCAGGTTCGCGGTACCCTCGTGCTGCAAJGGCCTGAGGGCAATCGATGCGCCGC TGTTGCTGATGTCCTCGCTGGACGCr-CTGGCTTCCCGGTCCCGGTCAGACCGCCTATGCCGCCG CCAACGCCTTCCTCGACGCCTTCGCCAGTCTGCGCCGGCGAGAGGGAGAGCCGGTGTACAGCG TTGGCTGGGACAGTTGGTGCGAGGTGGGCATGGCTGCTCGGGTCGCTGCCCGATCGGCCGACG AACGCGGCCGCCTGGCGCGCGAGGG-GATCAGCCCTCGCCAGGGTTGGCAGGCTTTGAGCCGGG CGCTCGCCCTCGACCCCCCCCACCTG(. ATGATCTCGCGCACCGACCTGACCTCGCGCTGGCACA GTCGATCCAGCCCTACGCCGGTCC CTCGAGCGAACCCGiAGGTGGCGCTGCCGCGCTGGACCG CATCCGCCTGCCAAGCCGTCATCGAG'CGTGTTTGGTGCGAGCACTTCGCCACCGCCGCCGTGC CTCCCGATGGCAACTTTTTCGAGC:-CGGCGCCAGTTCCTTCGACATCGTCCAGCTCAGCGCTC GACTTCAACAACAGTTCGGCCGAGATGTCAGCCACACCGTGCTCTACAGTCATCCCACCGTCG CCTTGCTGGCCGGCTACTTCGCCAATGACCCGACGCCGTCCGGTGCTGCTGCCGACGAACGCG ACGAAGCGGTGCGTCGCGGCCGCGAC'CTCTTGAAGAGCCGCCGGCGAGGAGTATGACCGTGGA GCACGAAACCGGATTCGAAATCGCC-GTCATCGGGCTGGCTTGCCGCGTTCCCGGCGCTGCCGA CGTGGCCGCCTTCTGGCGCAACCTGG3TCGAGGCCAAGGAGAGCGTGCGCTTCTTCGAGGACCA CGAGCTGCGGGCCCCCGGCGTGCC -- 7GAACTGGCGCACTCTAGCA GCCACTGCTCGCTGATGGCGAAGC-TTCGACGCGGACTTCTTCGGGTTCCATCCGCGCGAGGC CGCCTACCTGGACCCGCAAGTTCG3 C-TCCTGCACGAATGTTGTTGGACCGCGCTGGAGGATGC WO 00/22139 PCTIUS99/23535 84 CGGCTACGATCCCGCGCAGTACGC C:ACCCGATCGGGTTGTTCGCGGGCGTCTCCAGCAATCT CTCGTTCCTGTTCGACCGCATCGA- CC'GCGCGACTCCCCCCTGCAGAAGCGCTATGTGGCCGA GCTGAACGCGGCCTCCTTCOCCACC CAGATCGCCTACCGGCTCGATCTGAJAGGGGCCGGCCAT TTCGATTCAAACCGCCTGTTCGAC2T7CACTGGTGGCGATTCACCTGGCGGCGCAAAGCCTGAT CGGCGGCOAGTGCCACATGGCCTTGGC 7 -CGGC GGAGCGACCTTGGAGGTCCCCAAAAAGCCCGG CTATCTCTACCGCGAAGGCTACATC-,J -CTCGCCGGACGGCCACTGCCGGGCCTTCGACGCCGA CGCGGCCGGCACCATCTTCGGCGAC GG1-CGTCGGCATCGTCCTGCTCAAACGCTACCGCGACGC CCTACGCGACGGCGATCACGTGTAC -- CAGTGATCAAAGGCTCGGCGATCAACAGTGACGGCCA TCGCAAGGTGTCCTACACGGCGCCG-7 ZI-CGAGCGGTCAAGTGGCGGTGATCCGCGCTGCGCT GGCGGCGGCCCAGGTAGAGCCGCA-Z-:CCATTCGCTTCGTCGAGGCCCACGGGACCGGCACACT CGCCGGCGATCCGATCGAGGTAGA-77GTGCGGTCTGCGACGTCCGA CTGCGCCCTGGGTTCGGTGAAGAC CA-; ACATCGGCCACTTGGATGTGGCGGCGGGCGTGGCCGG TTTCATCAAGGCGGTCTTGGCGCTCGAGCGGCGCGTCCTCCCGCCCAGCCTTCACTTCGTCCG GCCCAACCCGGCCATCGATTTCAAC-GGCCCTTCTACGTTTGTCGCCAAJATCGAGCGGTTGAC GGAGAACGGGCGGTTGCGGGCCGGGGSTGAGTTCCTTTGGCATTGGCGGCACCAATGCCCACGT GATTCTGGAGGAAGCGCCGGCGCCGG3AGGCGAGACTGCCGGCCGGGAGCCCGCCAGGCGCGAG TCCGTTCCTGTTCCCGCTATCGGCC--AGACGCCGGATGCGCTGGCAGGCCGTTGCCACGACCT TGCCGACCACCTGCGGGCGCACCC-CAGCTCCTCCTGGCCGATGTGGCCCTCACTCTGCAGAT GGGGCGGGCGTCGTTCGCCTACCGC CATGTGGTCCAGGCTGCGACGGCGGAGGAGCTGATTCG CGGTCTGGGAGCGTTCCGACAGGA~- -CCATCCGCAAGAGGCGGAATCGAGTACAATGGGTGTT GGCAG''GCGAGGCGATGTCGCTTGAC CCGGTTTGCGGCTGTACGCCGATTGGCCGGTCTATCG GGAGCGGGTCGACGTCTGTCTGGCG-ATCGTCGCCAGCTGCGCCAAATCGACGGCCGGTCATT CCTACATGAGTGGATCGAGCOACCG IG' 'CGAGGTTCCTGCCGAATGGTCGACGGCGCTGGCGTT CATGTTCCACTGCGCGCTGGCGCAIG--CCCTGAGCCAGGCCGGCCTGCACCCGCAGCGCATGTG GAGCCGTGGGCTGGGCGGACAGGTCG-,-GCGTGGTTTTGGCCGATCCCTGTCGTTGGACAGC GCTGGCGCTGGTGTTGTGCCAGACA-C CGGTTCCCGGCGATGCCACACCTCAGCGCGAIkCGCTT GGTTCGGACACTGGAAGGCTGCCGG:z-TTCGTCCACCACGATTTTTGATTTCGGCAGACAGCTC GGGTLCGACCCCTGGACCTCGCCG-T-TCGCTCATGTCGATTTTTGGTGCGGTGGCCAAAGCGC CTCG-CCAATGAGGCGGAGCTGCGC':- ATGGAGCGACGCCGCGCCCGAGCTGGTGACCTTGGC GATCG-""GCCCATCCTTTCTCGAGGCC-7CCTCCGGGACGGTGGGTCTGGCGATCGACCCCAAGCG WO 00/22139 PCTIUS99/23535 85 ACCGATGACCTGTGTTCAGCGCACGGTGGCCGCGTTGTGGGAJATGGGGATGTGACGTGCGCTG GGCTGCGTTCACCTCGTCGACCGGGCGTCGGGTTCCCCTGCCTACCTATCCCTTCGTGCGGGT AATTCCCACGATCGGCGACCCCCT-TCGCGGAGCAGGCGCGGAGGATGACTTGATTGCGGCGAG CGCTTCCGCGTCGGCCGGATCGCCGCCCGAGCCGTCGGCAACTCGGCAGCGGAACGCCCACG CGCCCAGTCAAGCATCGCCTCGGCAACCACACCGGCTCCGTCTCATACGTCGGCCAGCGTGGC CGTGGCCACCATTCTCGAAACCGTCCGTGCCTATTTCGGGTTCGCCGCCGTGCGTTCCACCGA CGCCTTCTTCGAATTGGGCGCGTCC TCGCTGGATTTGGTCAACCTGGGCCAGCTCCTTTCCGA TCGTCTCGGCCGCGAGGTTCCGACCCTGCTCCTCTACOACCACCCAACACCGGACCAGTTGGC GCTGG'7-CCCTGACATCCGCGGCGCTCAGCGCAGAGGCGCCGCCCTTAAGGGGCGGTCATCGCGC ATCGACTTCCGGCACAGCCGCGAGCTCGGCCGCCTCCACCGCACCGACGTTCCCGGGGGACGC TCACTCGCAGCCCAGCTTCGTTCGC GAGCAGGACATCGCCATCATCGGGATGGCCTTCCGGGG ACCGGGCGCCGACGACCTGGACGCGTTCTGGACACCTGGTCGAGGGGTCGAGTCGATCAC CTTCTTCAGCGAGGACGAGCTGCTGGCGCGGGCGTCCCCCGCGAAJCATCTGGCCTCGACGCG CTCTCGCAGGGATATGAGTGTTGACGATTCGT TTCGGCGCGCGAGGCGGCGGTCATGGACCCGCAGTTCCGCGTGTTCCACGAATGCTCCTGGCA CGCACTGGAGCACGGCGGCTACGATCCGACCCGATGCGCGGCATCGATTGGCGTCTACGCCGG CGTGACCAACCACCTGCCTTGGCTGATGCGAACTTTGCCGCACCTGACCGAGGAGGAGCAATT CGGCGCGCTGCTCCTCACCGACCGCGAGTTTTTCGCACCGCTGCTCTCCTACAAGGTCGGCCT GCGC GGACCCGCTATTTCGCTGCAACCGCCTGTTCGACGTCGTTGGTGGCGATCGGCACGGC CTGTC -GCGAATTGCGCGCGGGTGCC TGTCAGATGGCCCTAGCGGGCGGCGTGACGGCCAGCAT CGAGC -GCTGCGGCTACTTCCACCAAGAGGCTACATCCTCTCGCCTGACGGCCACACGCGCAG CTTC GACGCGGCGGCCGCCGGCACGGTCTTCGGCGACGGAGTCGGCATGGTGCTGCTGAAJGCC GCTGGCCCAAGCCTTGGCCGACGGCGACACGATCCACGCGGTGATCAGGGJTCGGCATCAJA CAACGACGGCGCGCGCAAGGTCGGCTTCACCGCACCTAGCCGGGCCGGTCAGACCGAGGCGAT TCG-GG-CCGCGCTGCGCGACGCCGGGGTGGCGTCGAACCGCGTCAGCTACGTGGAGGCGCATGG AACCG-CGACCAGAATGGGCGACCCG,-'ATCGAGGTCGAGGCCTTGACCCAAGCCTTTCGCGCCGA AGCCG,-ACGGTCCGCTTCCGCCCGGC -TCCTGCCTACTCGGCTCGGTGAAGTCCAACGTGGGCCA CCTAACGCCGCGGCCGGCGTGGCTGGTCTGGTAAACCGTGCTGGCGCTCCAACACCGCCG CCTGC -CGACCAGCCTGTTCTACCAG TCGCCCAATCCACACATCGACTTTGCGGCGAGTCCGTT CCGZCGTGAACGGCCAGACTTCGGAT-TGGGTCGCGCCAGAGGGGACGCGGTTGCTGGCGGGAGT WO 00/22139 PCT/US99/23535 86 GAGTTCGTTCGGTATCGGGGGAACCAACGCCCACCTGATCGTCGAGGAGGCGCCGAAAGCGCT ACCGACGACAGCGGCACCTCTGTCGACGGAGCCGAATGACCTCGACGCGGGCGACGCCGACGG GCTAGTGCTGCCGATCTCGGCCCGCACGCCGACCGCCCTGGCGCACATCGCGACCAACCTCGC CAATCACCTGGAACGACATCCGACCATCGCCCTGGCCGACGTCGCCCTGACCCTTCAGCTGGG CCGTCGCCAATGGCCCCATCGCCACAGCCTGATCTGCCGGAATCGAACGGAGGCGATCAAGCT GCTGCGCGCCGTCGTCCACTCCGCGGAGGTGCCGCCAGCTCAGGCGCCGGTCTCGGATGCGCC GCGCTGTGTTTTTCTTTTTCCCGGCCAGGGCGCCCAATACCCGAGCATGGCCCGCGACCTGGT TCGAAACTGTCCCGACTTCGCCCTGCACCTGGACCCCTGCCTCGACCAGTTGGCCGAACTGCT TCCCGAAGATCCGCGTTGCATCCTGTTCGGCGATGGCCCCGCCGATCGGCTCGACCAGACGGC CTACACTCAGCCGCTGCTCTTCTCCGTGTCCTACGCCTTGGCGCGCTGGTTGGGCGATTTCGG CATTCGCCCCGATGCGATGATCGGCCACAGCCTGGGCGAATACGTGGCGGCCTGCTTGGCCGG GCTTTTCTCGCTGAGCGATGCCCTGCTGCTGGTGAGTGAACGCGGCCGCCTGATGGGCTCGGC CGCGCGCGGAGCGATGCTGGCCGTCCCCTTGCCCGAATGGGAACTGGAGGAACGCCTGGAGCT TCTGGCCGACGACCGAATCAGCATCGCGGCGGTCAACACCGCCGAGAGCTGCGTCATCGCGGG ACCCAGCGAGGCGATCGAGCGCTGCGCCCAGCGCTGGGCCGCGCAAGGCCTGACCTGTACGCC GCTGCGCACGTCCCACGCCTTCCACTCCGCGATGATGGAGCCGATTGTCGAACCCTTCGGCCA TGTCTTGGCACGGGTCACCTTCGCGCCGCCGCGCGCGCGCTGGATCTCGAACCTCGACGGCAA GCCGATCGATTCCGCGGCGGTGATGCAGCCCGACTATTGGGTGCGCCACCTGCGCCAACCGGT CCGCTTTCACGAGGGACTCAGTCACCTGTTGGCCGAGGACACCCATGCTTGGGTCGAAGTGGG TCCCGGCCGAACCCTGTCCTCCTTCGTCCGCCGCCACCCGGCCTACCGTCACCAGCCAATCGT CAACCCCATGCGCCATGCAGTCGAGTCGACGGGCGACGTGCGCCGGTGGCGCCAAGCGCTGGG CGAACTATGGCGGGCCGGCATGCCGGTCGCCTGGGAGCGGCAGCGGCGCGGCCGGCATGCCGG ACGACGTGTGCCGCTGCCGGGCTACCCCTTCGAGCGGCGGCCCTTCGCGGCCCGAAGACCGGT GGAGCTGGCGCAGCCCGCGCCCAAGGCGGAGCTGGTGAAAAACCCCGATCCCGCGCGGTGGCT GTACCGCCGCGTCTGGCGCCCTGCCCAGGCTGCGGCCGGCGGACTGGCGGTGCAGGCGACCGT TCTGGTCTTCGGCGACGGGTCCGAGCTGTGCCGCGCGGCGGTCGCTCAGGTGCAGCGCCAGGG GCTGAAGTGCGTCTCGATCACCGCGGGCCGCCAATTCGCGCGGGAGAGCGACATGCGCTTCAC GCTTGACCCCGCTGATCCGCGCCAGCTCGACCAGCTCTTCGCGGCCCTCGATGGCTCAGGCTC GCGGCCGCGGTACGTCCTGCACCTGCTGACCCTGAACCCGCCCCCGGATGCCTCGGCGATCAT CGCTCACAGCTACTACAGCCCGATGGCCTTGGCTCATGCCTTGGGCGCCCACGAGATCGCGCC WO 00/22139 PCT/US99/23535 87 TGTCTCGATCACCGTCGTCACCGCCG-GGGTCGTCGCCGTCGCGGACGAAGCGATTCGCGAGCC GCTGCAGGCGCTGATCGTGGGCCCGTGCCTGGTCATCCCGCAGGAGTTTCCCGGGCTCAGCGT TCGGCTGCTGGACGTCAACGTCGACG-'-ATCCGGCACCGCGTCTGGCGGAGCGGCTCGTGGCCGA GCTCTCGGGCACGGATCACATGGTG GCGCTGCGCGGCGGCGAGCGCCTAGTGGCCGATGTCGA TCAAGTCGATGGCCTCGGTGTGGGGATCGCCCAGGTGCCCTTGCGCCGCGAGGGCCACTACCT GATTCTCGGCGGCCTGGGCGATATC -GGCTACCACTGTGCCCGCTATCTGGCCCAAACCTACCG CGCCAAGCTGACGCTGACCGCGCGrnTCGTCACTCCCGCCGCGCGCGTCGTGGGAGCGAATGCT GCGCGAGGGAAACCTGGATTCCCGGC AGCGCACGCGCATCGAGCGCGTGTTGTCGCTAGAGGC GTGCGGGGCCGAAGTCCAGACGGCTG--CGGTCGACTTGGGCGATCGCCATCGCTTGGCCGATGT GTTCCGCGAAGCACGGGGCCGATmCG,-:GCGCCATCGCGGGCGTGATTCACTCGGCGGGGATTCC GGGACACGTCCACTCGATCGACGAC-TGGTGCGCGTCCGCGACGAGCCCATTCACCGCGAA GGTTCGAGGGCTGCACCACCTGGCCG'-AGGTCGTCGATCCGCTGAACCTCGACTTTTGTCTGCT GTTCTCCTCGCTCTCGACCGTCCTCG- -GCGGGCTCGGCTACGGCGCCTATGCAGCGGCCAACGC CTACATGGACAGCTTCGCCCGCCGCCACGATCGGCCGGACGATGTCGTTGGATCGCGTCAJA CTGGGACGCCTGGCTGTTCGAAGCCAJAGACGTCGTCGGTCGGCGCCGAATTGGCGCGCCTGGC GATCGTGCCCGAGGACGCTCCGGCCCTGTTCGCGCGGGTGCTAGAGCGACTTCCGCAATCGTT CATCGTGTCCACCGCCGACCTTCGGGCCCGCATCGACACTTGGATCCGGGACAGAJACCGCGT CCCGCCCGCCGAGATCCGAGCGGT'-CCCGCGACCGGACCTGAGCCAGGCGTACGCCCCGCC GATCGGCCCGCTGGAGATTCAACTCTGCGGGCTGGTCTCCGCCTATTGCCGGTTCGACCGGAT CGGGCGGGACGATTCCTTCTTCGAA-ATCGGCCTCAGCTCGTTCGACTTGATCCAGCTCAGCTC GCGCATTCACCGCATCACCGGCAGG"ATCTCAATACGACCCACTGTTCAGCTACCCCACCGT GCGCGCCTTGGCGCTCTTCCTCGGCGl GCGAACCGGAGGGGCTCGCGGCGGAGGAGCCCGCCAT GGAGAACCTGTGGCTGCAACGAAGCGATGCGACCCTCGATGAGTGAGACCGAGGTCGCCGACT GCGGCGCTACCGACCGCGGTCGAGCATTTTCCGCGCAGCGATCCGGGACGACTCGCTGAGA GCGCGATAGAAGAACGGAATCGTG--ATGATACGAACCACCGGATTGGATTGGCCGTCAT CGGTCTCGCTTGCCGCTTTCCAGG:TCACCCATCCCGACAGTTCTGGTCGAATCTGCGCGC AGGTCGCTCCGGAATCCCCCATTT r AGCGATGCCGAGCTGAGCCACATCCCCGCATCCCTGCG TCACCATCCGCATTACGTCAAGGC C'AAAGGCGCGCTGGACCACGCCGATTTCGAACCAGCCTT CTTCGGCTACTCGCCCAAAGAGGC C'-GAGGTGATGGACCCTCAATTCCGGCTCCTCCATGAGTG CTGCTGGGAGGCGCTGGAGTCAGGCG-:GCTATGCGCCGAGCCAATTCGCGGGTCGGATCGGCTT WO 00/22139 PCT/US99/23535 88 GTTCGCGGCGGCGGCCTTCAACGAC-GGATGGATCGCCGGTACCCTCGACCGGCTGCGCACCGG CGTGGGTTTGAGCTCCCTGGAAACCGCGTTCTTGACCCTGCGCGATTACCTGACCACCCAGAT CTCCTATCGGCTCGATCTGCGGGGCC-CCAGCCTGCTTGTCC1AJkCCGCCTGCTCGTCGTCGCT GGTGGCGGTCCAGCTCGCCCAGCAGGCGCTGATCTCCGGCGAATGCGCCCTGGCCTTGGCTGG CGGCGTGTGCGCGACCGATCCGCTGCATTCGGGATACCTCTATGACCCGGCAJCATCTACGC GCGCGACGGCGTCTGCCGACCGTTCGACGAGGCAGGCGCCGGTACGGTCTTCGGCGACGGGTG CGGCATGGTCCTGCTCAAGCGGCTG AGCGACGCCCAGCGCGACGGCGATACGATCTGGGCGGT CATTCGCGGGGCGGGCGTGAACAACGACGGGCACCACAAGGTTGGCTACACGGCTCCTGGCAC GAGGGGCCAGGTGGCTTTGCTTAAAAGTGTTTATCGCGCGAGCCGGGTCGACCCGGCGACGCT CGGCTACCTGGAGGCCCATGGCACCG-'GCACCGCGCTCGGCGATCCAATCGAGGTCGAGGCGCT TACCCAGGCCTTCGCCAGCAAACGTC -GCGGCACCTGCGGCTTGGGCTCGGTCAAGGGCAACCT GGGTCACCTCAACACGGCGGCCGGCATCGCTGGACTGATCAAJGGTGGTGCTGGCGCTGAAACA TCGCGAAGTGCCACCCACCCTCAATC TGCGCCGTCCCAJATCCGAAAATCCGCTTCGACGAGAC GCCGTTTTTCCCAGTCGTCGAGTTGCAJACCCTGGCCAAGCGGGACCGGCCCCTTGCGAGCCGG CGTGAGCTCCTTCGGCATCGGCGGT ACGAACGCCCACGTCATCCTCGAGGAGGCACCGCCGAC GGCCAACCCGGCGCCACACGGCAGATTCCGACTGTTGCCGCTTTCGGCCAAGACACCGGCTGC GCTCGAAGCGAAGCGCCGCGATCTGGCCGGCTTCCTCGAACGCCACCCGGAGACCTCCTTGGC CGACCTCGCCTTTACCCTGCAACGCGGCCGCGAGGTCTTCAGTCACCGCGCCTGCCTCGCCGT GGAGACCTTAACGTCCGCGCGCACGCGGCTGAGCGGCGAGTCGTCGAGCACTTGCGTGGTGGG CCCCGCGCCCAGCGCCATATTTCT-GTTCCCTGGTCAAGGCAGCCAGCTCGCCCGGGATGGGCCG CGGT CTGTATCACCATTTCGAGCCC TTCCGCACGGCCGTCGATGCCTGTCTGCGCGAGCTGGA GCCAGGACTGCGGCAAGCGCTCAGC GCCCATTTCGATCCGAATCGCGGCGCGGACCCACCCGA TTCGACGACCTTCGTCCAACCCTTGTTGTTCCTCGTCGAGTACGGGGTGACCGAGTGGCTACG CTGCTTGGGTGTGCGGCCAACAATGGTGTTGGGTCACAGCTCTGGCGAGTATGCCGCAGCCTG CGTCG- CGGGCGTTCTGTCGCCGTCCGCGGCGGTCTCGCTGCTGGCCGAGCGCGAGCGGCTGCT GCGCGACCTGCCAGCCGGCGCCATG-CTCGGCGTCCCGCTGGCCGCCGAGGCGCTCGAGGCGAT GTTGCCCGACGCTCTCGATCTGCC -GCGATCAACGGCTGTCAGCTTTGCGCCGTGTCCGGGCC GGTCGCGGCGGTCCACGCCTTCAAGG1-CCCAACTGGAAGCCGCCGGACATCACGCCCGCCTGTT GCACACCGATCGCGCCTTCCACTCG"-CGGCTGGTAGCACCGGTGCTTGACCGGTTCCAGGCAGC CGTTC -AACACGTGGAGCTGCGGCG'-C CGCAAGTACCTTACCTCTCGACCGTCAGCGGGCGATT WO 00/22139 PCT/US99/23535 89 GGAGGCGGATGGGCCGGCGAACCCGCACTACTGGGTGCGTCACCTGCGCGACACGGTGCGGTT TGGTCCAGCCCTGGAGGCGCTGCCGCCGGTGGATTCCTTCGTGTGCATCGAGGTGGGACCAGG CTCGGCCTTGAGCACCATGGCGCGCGAAACGTTGGGTTCCCAGGCGCGACTGATTTCGTTGCT GCCGCGGCCGCGAACGGGGCAAATCGAGCCCGGTCCGGTATTCGAACGACTGGCGGCGCTTTG 5 GCGCAGCGGGTTGACATTGGATTGGTCTAAATTGACGGGCGGCGAAGAGGGTCATCGAATTCC CTTGCCAGTCTACCCGTTTCAGCGCAGCCATCTGTCGAGCTCCCTGGCGGCGGGCCACACGCC TTCGTCGCGGCCTGCAGTCGAATCAGGCGCCATCCTTGCCGAGCGATCCGCAGGGGAAAACGC TGAAACCCGGGATTGCCCGCTGCCAACCGCCACGCTCGAGCCCAAGGCGGTCGCTCCGGCCCC ACTCGAGGCTACCGACGCCGCAGGTACTCGCGAGCGACTGGCCGAACTTTGGCGCGAGTTGCT 0 AGGGTTGACCTCGATTGGGCCCGACGACCATTTCTTCGACCTGGGCGGCCACTCGCTGACCGC CACGCGGCTGCGCGCCCTGATTCACCAGCGGTTCGATGTCGATCTCGGGCTCGACGAAATCTT CGCTCATTCGCGTCTCTCCCAGCTGGCCGCCCGTATCGAGGCGGCGGCCAAGAGCCGATTTTC CTCCATTCCCAGCGCGCCGGACCAGGACGACTATCCCTTGTCATCCGCCCAGCAGCGGATTCA CAGCATCGTCACGAGGGCCGAGGTCGGCACTGCTTATAATTTTCCGATCGTCCTCGAGCTGCA GGGCGCTCTGGATCGAGTGCGATTCGAGGCGACGTTCGCGGCATTGTTCCGGCGTCATGAGGG GTTCCGCACCCGCTTTGTGATGCGCGATGGCGGGCCGCGCCAGCGCATTGTACCGGACGTGGC GTTTCGCCTGCCGCTCACCCAGGTCGAGCCAGAGCAGGTTCCCGGGCGCATCGAGGCCTTCAT CCGTCCCTTCGATTTGGAACGCGCGCCGCTGTTCCGCGCGGAGCTGTTGCAGTTGGCCGAGCA GCGCCATCTGCTACTTTTCGACATGCACAACTTAATTGCCGACGGTATCTCGCTCAACCTGTT D CGTCGCCGATTTCGCGGCCCTGTACCATGGTCGTCCGCTGGCGCCGCTGAAACTCCGCTATCG CGACTATGCCGTTTGGCAAGAGGCGCGGCTGGCCTCCGATGACCTGCGCAGCCAGCGCGAATG GTGGCACCGGCGGCTTTCGCCGCCGGTCGCCACGCTGGCGCTCCCTCCCGATTTCCCGCGTCC GGCGGTGCGCCGCTACAAGGGCCGTAATGTGGTGTTCCACCTGGACCGGGAGATCCGCGACCG CCTGGTGGCCCTGGCTCGAACCCAGGGGGTCACCATGAACGTGATGATGCTGGCGCTCTGGGC D TGCGCTGCTGCATCGCGAAACCGGCCAATCGGAGCTGGTGGTCGGATCGCTGCTCGGCGGGCG GCCGCACAGCGAGCTGCATCCCGTGATCGGGCTCTTCACCAACTTTTTGCCCTTGCGGTTGGC GGTCGAGGGATCGACCCGCTTCGATCGCTTCCTTGCCGCTTGCCACCAGGTGTTTCTCGAAGC CTATCAGCGCCAGGACTATCCGTTCCACTTGTTAGTCCAGGAACTCGTGCCGGTCAGGGACCC GTCGCGGTCGCCGCTGTTCCAGACCTCGCTCGTCTACCACAACGAAATTGACGGCAAGACCAA D GCTGGAATTGGAAGGGCTGAAAGTCGAAGTGGTTCCCTTCGAAAAGGGTGTGGCGAGGCTGGA WO 00/22139 PCT/US99/23535 90 TTTGAAGCTGGATGTGACACCTTTTTCCGACCGACTCGAATGTGTTTTGCAATACGACTTGGA TCTGTTCTGCGAGGAGACGATGCGCGGCCTGATCGCGCGGTTCCAGGCGTTGGTGGCGGGGCT TGTCGCCGATCCGGCGCAATCGCTCGCCGCCGCGAGCGTTTCCGGGAAGCGGGCGCTGCGCGC GGGCGTGGCCACGGCAAGCGAATCGTCGCCGCAGTCACTGCCGCCGCAACCATCGACGGCGTA 5 CGCCACTCCCTCACCGCAGTCACCGTCGCCGGTAGTCCTGACGGGACCCGCCGACCTGCCCGC GATCTTGGCGGCCTACGTGGGGCAGAACCCCCATCCGTTCGCGATCCATCGGGGTCTCATTTT GGAGGCGCCGCTGGGGTTGCGAGCGCTGCGGTCGGCGCTGGACGCAGTGCTCGGAGAACACAC CCATTGGCGCAGCGTGCGTGCGGGCGATCGCGCGCGGCGCGTGGATAAGTTGGAATTGACCAG CCTGGTGCGGCTCGACGACCTGCGCGGGTTGGTCAATCCTCAGGCGAATGCCTTCACCCTGGC D TTGGCGCGATCTGGCGATGCCGTTCGGGGAGGGGCGTCCCCTGTGGCGACTCCGCCTGGCGTG GTCGGCTCCATCGCGCTGGTTGCTATTGCTGACGGTTCATCCATTGATCGGCGACAACGGCAC GGTCGACCTCTTTCTGGCGGCACTCGCCGATCACCTGCGCCGCGCGTCCGCTTTTCCCGTAGC ACCGCTCGATGAGGCCGAGCTGGAGGCGGAGCTGAAGTGGGGAGAGGAAGGGGAGGGCCTCGG GCTGACCGCGATCGCGCCGGTCCTGGGCCAATTGCGCGAAAGTCGGCTGAGTCCTGTGGCCCA D GATGTGGCTGGACGAGGTCTGTCGCCGCCACGACCTCACCCCGCTAGAGGTCTTGGCGGCCCG GCTCCTCGATTGGACACGAAGCCACGGTCACGGGTCGATCGCTTTGTGGACGCCGCTGCCCGA GGACCATCCGCTTCGCGATGAAGGCCGCTGCCTCCAGGTTCGCCTGCTGGAGGGGCCGCCGTC GCAGCGAGGAGCGGGCGATCCAAGCTGGCTCGAGCAAATCGCCTTGAGACGGGGTACCCCTGC AACGGAGGTCGTTTGCCCTACTCCGACCCAACGGGCACCCATCGACCTCGCGCTGGCCTGGCT GCCGCAGCCGCCTCTTCACGGTTTGGTCGGAACCGTTCAGCCGTGGCCGGAATCTCCATTGGT CTGTCCGTTTCCCCTCAATCTCGCGTTCCGGCCAAGCCATCCAATTGCCTACGCGCTCAAGCA CGAGGCCACGCTCGCGGTCACGGCACGGGCGCGCGATCTGATGCGTTTCCTCGACGGCTTGGG CCCGGAAAGCTGAAGATTAGCATAAGCGCCCGGCCAAGGGCATCCTAGGATGACGCAAGCCTC GGCCGCGTCGACGTCCCAGGTCGCGCCGGAGGTCACCCCCGGCCGAAAGGACGACGATGACGA TCAAATCCGAGATGTCGGCCGTTGCTCACTCTGCGGAGAGCGGCTTCCGCGCTGGGCCACGCG TGGGCGGCGCGATGAAGCGGGGCCGGACGCCGGAGCAGGCCGGCGTGAAGCTGCTCCGCGCCC CGGTGAAGCGGAAGTGGCTGCCCCCGGCGCCCGTCCTGCGCCTGAGCGAGCGGCGTATCCCGG AGGTGTGGGCAGGCTACCGCGCGAGCGCGGGATGACCCGAGCCCCGCCCGCCGGCGCGACCAT GACGCCGCCCCACGGGGCGAGTCGTCCGGCGCGCCGGCGCGCGTCGGGGCTTCCGCCGCCGGG CGGGCAGGTGCAGGATGGTCGGGCATGGTGACGCGTCCGACGTCCGACGGCATCGAGGACGAG WO 00/22139 PCT/US99/23535 91 CTCGCGCCGTTCCCCCCGGTCCTGCGCGGCTGGCTCATCGAGGGCGAGCTCGGCCGCGGCGGG ATGGGGCGGGTGTTCCGGGCGCGGCACCCGAAGACGCGGGCGCGGGCGGCGATCAAGGTGCTG CTCGGCGACTACGCCCGCCGGCCGGACGTGGTGGCCCGCTTCCGGCAGGAGGCGATCGCCGTC AACATCATCAACCACCCGGGAATCGTCCGCGTCTTCGACTCCGGCGAGCTCGAGGACGGCTCG CCCTACATCGTGATGGAGTACCTGGACGGCCGGGGGCTGCGCGACTGGGTGCAGGCCGTGCCG CCCGCGGAGCGGCCGCGGCAGGTCGTGCGGCTCGGCTACCAGATCGCCTCGGCCATGGCCGCG GCGCACGCGTCCAAGGTCGTCCACCGCGATCTGAAGCCGGAGAACATCATGGTGGTCGAGGAC GAGCTCGCGCCCGGGGGCAGCCGCGTCAAGATCCTCGATTTCGGCATCGCGAAGGTCCTCTGG GGAGGTCTGCCCGAGGTGCTGGAGCTCGAGGGGAGAGGCTCCCTCGCGCCCGCGTCCGCGTCC ) ACGATCCGCACCGAGCTCTCGACGCGGCCGGCGCCGACGGTGGGCGCCACGACCGGCCCAGAG AGCCCGCTGGGCGCGAGCGCCACGCCAGAGAGCGCCCTGGGCGCGAGCGCCACGCCAGAGAGC GCCCTGGGCGCGAGCGCCACGCCAGAGAGCGAGGCCCACGAGGAAGACGCGCTCCGGAGCCTC CCCGTCGTGACCAGCGGCAGGCCCGCGATCCACCCCGCGCCGGTCGAGATCCCGCCCGAGGCG GTCTCCTCCGCGGCGTCGCGCGGGTCGCGCGCGTCGATCGAGCCAGGCGCGCCCGCGCCGCAG AGCGAGGGCGCGGGACAGCCCACGATGCCGTTCACGCAAGAGGGCGTGTGGGGCCTCGGGACG AGGAGCTACATGGCGCCGGAGCAGGAGCGCCACTCCGGGAGCGTGGACGTGAAGGCGGATGTC TACTCGCTCGGCGTCATCCTCTATGAGCTGCTCGAGGGGCGGACGCCCGACGCGCCGAGCGCC GCGTGGCCGCCCCCGATGAGCGCCGCCACGCCGCCCGATCTCGTCGCCCTCGTCCACCGGGTT CTGGCGTTCGATCCCGATGCGCGGCCGCGCATGGCGGAGGTGGCGAGCGCGCTTCACCGGCTC GGCCGGGCGAAGAAGGAGCTCGACGAGGCGCTCTCGAGGTGGGTCGTCGGCGGAGGGGCGCCG GGGCTCTTGCCGTGCGGCTATGCTCTTCTCGAACTGGTCCTCCTGGGCCCTGGGAACTTATAC GATTCTTTCCAGCCTGTAAGTGCATTTTTCTTTCAATATCGTCCTCTCTTCATATACGAGGTG AGTTCTCTGAGGTCCTCCTATAAGTCTGGGGTGTCCTATTCGGCCTCTTACTTGTTACTTCGC CTTCTTAGGAGTTTTTCCTTAATTTTGCCCTCTTACATTCCCGTATTCATTCTAACTGGGCCC TATCTCATTCGCTAATACGTTTCTGTATTGTGTACATCTCCTATCATGTGTCAATACTTGTTT CTGTTTATCATTATTCTTATTGTTTACGCTCTTATTTCATTCATAGTATAACATTAGTTTACT GATTATCGCACTTGAATTCGCG or its complementary strand, WO 00/22139 PCT/US99/23535 92 (b) DNA-sequences which hybridise under stringent conditions to regions of DNA-sequences according to (a) encoding proteins or to fragments of said DNA-sequences, (c) DNA-sequences which hybridise to the DNA-sequences accord ing to (a) and (b) because of a degeneration of the genetic code, (d) allele variations and mutants resulting by substitution, D insertion or deletion of nucleotides or inversion of nucleotide segments of DNA-sequences according to (a) to (c) , wherein the variations and mutants offer isofunctional expression products.

8. DNA sequence according to claim 6 selected from the fol 5 lowing (a) open reading frames: Nucleotide Position D ORF1 1666 - 1 Seq ID No 3 ORF2 1605 - 3338 Seq ID No 4 ORF3 6100 - 3398 Seq ID No 5 ORF4 7110 - 6374 Seq ID No 6 ORF5 9590 - 8433 Seq ID No 7 ORF6 11393 - 9855 Seq ID No 8 ORF7 13656 - 12712 Seq ID No

9 ORF8 15374 - 18984 Seq ID No 10 ORF9 20003 - 27889 Seq ID No 11 ORF10 28251 - 29402 Seq ID No 12 ORF1I 31720 - 30401 Seq ID No 13 WO 00/22139 PCT/US99/23535 93 ORF12 31982 - 32932 Seq ID No 14 ORF13 33128 - 33613 Seq ID No 15 ORF14 33661 - 34007 Seq ID No 16 ORF15 35611 - 35255 Seq ID No 17 5 ORF16 37856 - 35730 Seq ID No 18 or DNA sequences complementary .to said open reading frames, (b) DNA-sequences which hybridise under stringent conditions 0 to regions of DNA sequences according to (a) encoding proteins or to fragments of said DNA sequences, (c) DNA-sequences which hybridise to the DNA-sequences accord ing to (a) and (b) because of a degeneration of the genetic code, (d) allele variations and mutants resulting by substitution, insertion or deletion of nucleotides or inversion of nucleotide segments of DNA-sequences according to (a) to (c) , wherein the D variations and mutants offer isofunctional expression products, and peptide sequences corresponding to said open reading frames SEQ ID No 19 (>ORFl) VDPEREAVTLGLAFNRAQGRTYARGPEAAEYIGTAMRAADVIEDRFEIERLAVSGGMGDVYR ARDRVSGQAVALKVLQGASANDLRRFAREAEALVTLRLPGVVQYVAHGVTGAGRPYLAMEWLD GVTLEERLAGAPLTLAESVALAARVATTLGAIHWLGVVHRDLKPSNLMLVGGAVERVTLLDFG IARHLRLAPTLTSPGAVLGTPGYIAPEQVRGDAPVDARDVFALGCVLFQCLAGRPPFLGNSAL ALLMRVVLEEPPRLGELRDGIPEPLERLVARMLAKNAGERPRDGAAAAAELAAVAGEGLSIGA SAVAAPAAPGEAITTAERKVMCVILAEDGGAEAGATLSEDDGAAPAEALRDIAARHGGRLDRL WO 00/22139 PCTIUS99/23535 94 QARWWLVALSGAESPTDLATRAAHCALALRAALGGVPVSVATGLAEVEARLPVGELVDRVAQL IAGRDGLSPPEIRLDDATASLLASRFETVQGPGGCWLRGPKEEPDAVPRLLGKPTPCVGRERE LSQLATEWRHCVDEPSANAVVVVGAPGLGKSRLAWEFLRTLEQREGAAI SEQ ID No 20 (>ORF2) VRPCARLNASPSVTASRSGSTAAGSVHASTSACVEQPATGRTQPASPRWPPGAAALRLTSAMP RWFNTAGPCNPADHYMLPAEERLPAVRDLVDRKAYFVLHAPRQIGKTTSLRTLAQDLTAEGRY VAVLVSAEVGAPFSDDPGAAELAMLAEWRGTAGAQLPADLRPPPFPDAPAGQRIGAALRAWAQ AAPRPLVVFLDEADALRDATLVSLLRQIRSGYPDRPRDFPHALALVGLRDVRDYKVASVDSGR LGTSSPFNIKVESLTLRNFTRDEVATLYAQHTAETGQVFRPDAVDPAFELTQGQPWLANALAR QLVEVLVKDPAQPITSANVDRAKEILIERQDTHLDSLVDRLREPRIPAVIEPMLAGTALPSVP PDDLRFAIDLGLVRMTAEGGLDVANPIYREIIVRELAFPIRASLPQIKATWLTQDGRLDADRL LDAFLSFWRQHGEPLLGAAPYHEIAPHLVVMAFLHRVVNGGGTVEREYAIGRGRMDLCVRYAG ETLAIELKVWRDGRPDPVAEGLAQLDEYLAGLGLDRGWLILFDQRSGQPPIAERTRREPALSP AGREVAVIRA SEQ ID No 21 (>ORF3) VTIKKTFRSIDPATLPKHFDSPVAELRLADLWEADGTYRYDPSRPREETFVVDTPPPTASGSL HIGHVFSYTHTDVVVRQRRMRGFNIFYPMGWDDNGLPTERRVQNYFHVRTDVRTPYERGLTLP QAAPETIKKEPPRIVSRPNFIELCHKVTREDEQVFKALFRRVGLSVDWRNEYATIDDHCRRTA QLSFLDLHEKGHLYSVFAPTMWDVDFQTAVAQAEVEDRPQSGAFHDIAFAVEGTAEELVIATT RPELLAACVGVTAHPEDPRYQHLFGKTALTPIFRAPVPIFPSPLVDREKGTGILMVCTFGDAT DVIWWREQKLPLRQMLGKNGRVLPVTFGEGAWESRDPAAANAAYAPLQGRGVKQARAAVVELL RREEHAAAPGRGPALRGEPRPIERAVKFYERGDQPLEFVPTRQWFVRLADKKAELLEYGDKIK WHPDFMRLRYRNWTEGLQGDWCISRQRYFGVQFPVWYPLDAEGNPDHSRPLLATREMLPVDPT VDVPPGYEASQRDQPGGFTAESDVFDTWFTSSLTPQISSHWGDDPARHARLFPADLRPQAHDI IRTWAFYTIAKAMLHESSVPWHHVAISGWILDPDRKKMSKSKGNVVTPMHLLDTYSSDAVRYW SASARLGTDTAFDEKVLKIGKRLVTKIWNASKYVLSQSAEVHPISEELDRALLHKLSAVVDDA TRSFDEHEFAAALERTEDFFWRWFTDAYLELAKARARGEGGAGEAARGSAVAALRLGLSVLLR LFAPVLPYITDEVWRWVYAEETGDTSIHRAKWPSAADFAAVAAPSDPGLLDLAAAAMAAVNKR WO 00/22139 PCT/US99/23535 95 KSELGASVGRVVTDLALGANAATLARLKPALGDVLTAVRAGAHALVRPELADGEVLVVRCELE PAAAAAAGAGGAAASEE SEQ ID No 22 (>ORF4) 5 MIHAEPFEARLVAARPLSPFVRELSFERADGRSFLFEAGQWVNLVLPLPGGEVKRAYSIASAP DGSPRFDLAVTLVQGGAGSEHLHRLEPGATLRAIGPHGLFTRDPGDSAPSLFVATGTGITPLR SMLRASLRAGLAAPHLWILFGARFEEDVIYRDELEALARGSDRIRYEITLSRGGPSWAGRRGY VQAHVPELYRELAEKSGDPAPHVFICGLDRMVSSVRELARGELGVHRKHVHVERYD 0 SEQ ID No 23 (>ORF5) MKSLPSDRAARLAQSDIRTMTLACA:KVHGINMSQGVCDTPVPSVILQAVKEAMDRGCNTYSRF DGIVELRHAIAAKLARHNGIAADPETDITVSAGATGAFQATCMALLNPGDEVLLFEPFYAYRA QAILAVEAVPRYVTARSLSWNVDGDELEPAITPKTKAIVVNSPGNPSGKVFGRMELEQIADLA CHHDLMVITDEIYEYFIFDGREHVSVASLPRMSERTITIGGYSKTFSITGWRIGYSVADARWA 5 KAIGAMSDLLYVCAPTPLQHGVAAGIRGLPRSFYTGLAQGYERKRDRFCRALEKAGLPPCVPQ GTYYVLADVSRLPGRTGRERAIYLLDETGVAGVPGDAFFEGTQGSRFMRFCFAKTDEDLEEAC QRIEQLA SEQ ID No 24 (>ORF6) 0 VSDPRKERLGDMDLEEFRRIGMR IIDWAADYLGHPDRYPVFPAIRPGDVKGRLAPTPPVEPEP MDAVLTDFEQIILPGITHWNHPRFFAYFANTASGPGILGELLAACLNVNVMLWRTSPAATELE ELVLSWLRQMLDLDAGLHGAIMDTASTASMVAIAAARDSAEPTIRLRGMAGQRRMRLYASEQA HSSIEKAAITLGIGQEGVRKIPTDPAFRMVPEALRAAVVEDLGAGLRPFCVAATVGTTSTTSV DPIPAIVSVCREHGLWLHVDAAYAGMLAAIVPEHRDVLAGCEGADSLVVNPHKWLFTPMDCSVL YVRDADRLKRAFSLVPEYLRTEGDVTNYMDWGIQLGRRFRALKLWMIVRYFGHEGLAARIREH LRLGQQLAQWVDADPDWERLAPTP'STVCFRMRPSALACIMRSADEAERESIERELDRLNEAL LDEVNKSGRVFLSHTRLHGRYTIRVAIGNIRSDEVAVREAWECLRAAGARLCADERFVSCSRS ADEGRGKS WO 00/22139 PCT/US99/23535 96 SEQ ID No 25 (>ORF7) MRREEPVLEAFYERYCAAPRETSYHVELPVDVELHQEAAPALPQARSLELAGRVALVTGSSRG IGKAIALRLAEQGADVAVNYHSNKDAAEQTAAEIRALGRRTMVVQADVTRPNAAAELFSSVEA QLGPIDILVNNVGDFFFKPLAAMTDDEWRNVMDSNLSSVHYLCRAAVARMRQRKSGRIINIGL SPTYAIRGAPNVAAYSIAKTGVLILTRSLATEEAPHGILVNCVSPGLIDNGYLPPAQKEWMER RVPMGRLGPASEVADAVAFLASDPASYVSGANIAVAGGWDWTDRGTEHDRRVDLFIGHEEP SEQ ID No 26 (>ORF8) MSGRFPGARNVEELWQKLRAGVECVVTFTEAEALAAGVSREMLANPSYVRRGAPLDGVELFDA SFFGFSPREAESMDPQQRIFLEVAWEALERAGYDPDAHSGPIGVFAGSAPSGYHSLAQSDPEI LGALGHYQLTLNNDKDYLTTHASYKLNLRGPSVCVQTSCSTSLVAVVMACQSLLNHECDMALA GGVGIHAHQRRGYLYQENGISSPDGHCRAFDVAAKGTVGGSGIGIVVLKRLADALADGDHVHA VIRGAAINNDGSSKIGYTAPSVQGQAEVIGMAQALAGVEPDDISYIEAHGTGTPLGDPIEIAA LTRVFRAKTARRQFCAIGSLKTNLGHLDAAAGVASLIKTVMALEHRELPPSLHFERPNPKLEL ESSPFYVNTRLTPWHAARGPRRAGVSSFGIGGTNAHVVLEEAPAPPPSGPSRRWQLLTLAARS EAGLARATADMIEHLDRHSGTSIADVTYTSHVGRRAWPFRRAVVGESAADLRAALASEGSPRS ISSCQAARERPVVFLFPGQGAQHLFMARELYEVEPIFRQSLDRCAELLRGPLGLDLRQVLYPA EGQRDDAEQELGRTAIAQPALFAIELSLAKLWMAWGIVPQAMIGHSVGEFAAACLAGIFREED ALRLVAERGRLMQQMPPGAMLAVPLAEPELAPYLSDDISLAAINGPALSVVAGPIEAIDALAA ELLDHGLSCRRLHTRHAFHSKMMAPVVDAFTRCVSAVERRPPSGHFLSTLTGGWISPEAATIP AYWARQLVEPVRFAQAVRQLLSESTWLWLELGPGQTLSPLVRQQARADGGQVVVASLPRAKDA GADHLAVIEALGRVWSAGGTVDWKRFHEGEARRRVLLPTYPFERQRYWASPRHTSAPPEAIIK PLLAKNPNVADWFFLPAWRRSDPPVSFDAQAVTTRRSTWLVFIGDEGLGAALVEGLARRGHEV VAVVTGERFEQTGTQRYTIDPAANGDVASLFARLEIEGRMPDRIVHAFCTSPADGARIERGAA LEIERRLGFDSLLLLAQVIAAQRHPKPLMLGVITTRAHSVIGTEIIEPLRALVLGPCRVIPQE IPHVSCRNIDIDLPGEGGRAEIAARLIADLERESPDSVVAYRGGRRWVESIELTDVGRRSAGA APRLRQRGAYLITGGLGGIGLVAAELLAREAHARLILVGRTGLPARQGWDDWLAAHGAGDATS RKi LRIRALEEAGAEVKIAAADVSDFNAMRSVIEEARTRFGRIDGVIHSAGIASGGMIQLRTP MAAWRVMAPKVGGTLVLDALLRDERPDFLLICSSLASLVGGATQIDYCAANAFLDAYAQSREG EEGCRVISVQWDTWSDVGMAVDFKLPADLQEGRRESLKRGISSSEGAEVLGRILSAGMSGPLA WO 00/22139 PCT/US99/23535 97 ICTSDLPAYKQSVTTRRSQHEQTPAARPMHSRPTTTGAYVAPETETERRIAAIWQDLLGLEQV GANDDFLQLGGHSLLATQVLSRVLQTLKVGISLPQFFDAPTVAGLSRLVDAARAEGAGPVAPA IGRVERDAYRIKPPAAEQAARTKP 5 SEQ ID No 27 (>ORF9) MEPVGGVDMNQPAKQQETCVFPTSFAQRRLWFLDQLEPGSAVYNMPASFRTRGPYDVDSLVRS VNEIVRRHESLRTTVDVIDGEPVQVIAPSLRIEVPVVDLSEIDEPEREAEARRLMAEESRRPF DLTRGPLLPAKLLRLGEADHVLILTMHHIVSDGWSMDVLFKELSTLYAAFHEGRPSPLPELPI QYADFAVWQRELLQGEVLESHLGYWREHLRGAPTLLELPMDRPRPPAQTFRGSQpAFRLPLSL D QQAVQALSRQEGATPFMTLLTAFSVLLSRYARQSDLVVGTPIANRTRAELEGLIGFFVNMLAL RIDLGGDPSFRELLGRVREVTLGAYAHQDLPFERLVEELSPGRSPSHSPLFQVSFTLQNTPMD ATNRADIASGGAPLVEMKAAKFDLILELSESPQGLLGTFEYNTDLFDAGTIERMAGHLEVLLS SAVAAPDRPIAELPLMGAEERSRVLVEWNSTAALYPEDHCMHELFEQQVERSPEATAVLLQQQ TLTYRELNMRANQLAHHLRSLGVGPEVRVGLYLERSIETVVAILGVLKAGGAYVPLDPTYPSE RLGLMMADAAPSVLLTQASLLSKLPPHGDATLVQLDALHEALSRLPHHTPRSGVTAQNLAYVM YTSGSTGRPKGVLVEHRGLCNLPTVQAKLYGIAPGDRLLQFAPLCFDTSFCEIALALLSGATL VMGTADELLPGPPLVELLKKHAVTAMLLAPTVLAALPEQQSAALPLRVLTMAGEACPAELVKR WKAPGRRLFNSYGPTETTIWASSAADLSDERIPPIGRPIANTQIYVLDEALEPVPIGVPGEIF IGGVGVARGYHGRPDLTAERFVPDPFGQTKGARLYRTGDPARWLPDGNLEFLGRNDEQVKVRG VRIELEEIRAALLKHPAVAQAVAVVREDTPGDKRLVAYVVGRGGARVTAAELRQSVSERLPAT MVPSSFVALDALPLTPNGKVDRRALPEPEQSAGGEDHVAPRNAVEEELARIWASVLRLERVGV HDNFFEIGGDSILSIQIVVRAQQAGLRLTPRQMFQHQTIAELSTVARAVEAVHVEQDPVTGPA PLTPVQRWWLEQEAAEPHHFNQSIFLEVRERLDESALEQAIAHLIDHHDALRLRLARDERGAH QVFAAPGGSTPFQRVDLGALPSAEQISAMEKAASEAQASLDLAAGPVVRAVLFDLGEVAPQRL LVIAHHIAVDSVSWRILLDDLFGAYEQARRGEAVRLPPKTTSVKRWAELLTEHAGSEAVKAEL GYWLDSSRRTVAPLPVDRRAGEDVWGSARHIVVSLTPEQTEQLLREVPQAYRTRIDDALLTAF AQAIARWTGSPAVLLDLEGHGREELAGVDLTRTVGWFTAMYPILLRVDAADPGEALKSIKEQL RAVPGRGLGYGLLRYLRSDTIAEVRALPQAELCFNYLGQLDQAIPEAAPFRPAREYQGSERSP GAHRAHLIEVNASIANGRLYATWTYSERRHEPETIERVAASFVTALRALIAHCTLPEVGGNTP SDFDKVRLRQETIDALDAIDAGPGPSARGSRIEDVYPLSPLQEGILFHTLYATDYTAYVEQFH WO 00/22139 PCT/US99/23535 98 WTLEGDFDAEAFTRALQDVVARRALRTSFAWERLDAPLQIVRTGAVLPVEHQDLRGLAAEEQ TAHISRYVEAERQRRFDLRKAPLMRAGLLRLRKDAWCLVETIHHLILDGWSTQILLKEVFTLY EAHRGHRGHLALELEQPRPYGDYIGWLAKQDQVRTAAFWRRELEGFSAPTPLGVDRAVPHDDG GPRFGWRRIALSGDDAARLAAFARQHQLTMSTLVQGAWALLLSRYSGDPDVLFGMTVSGRSAP IPGIERMTGLFINTIPVRVREPADASVLAWLKALQEHEAELLEHEHSPLVEVQAHSDVPRGTP LFESLVVFENYPVQVIFEAPPVEGPTRAEEGLRMIDAQYISDPPYPLTVVAAFHGTLYLNIGY ERRRFDDQAVERMIGHVTTLLRGFVQRPETSVRDLPLLTAEEERTQLHAWNATAAPYPEGHCM HELFEQQVERSPEATAVLLQQQTLTYRELNIRANQLAHHLRSLGVGPEVRVGLCLERSIETVV AILGVLKAGGVYVPLDPTYPSERLGLMMEDAAPSVLLTQTSLLSKLPPHGDATLVQLDALHEA LSRLPHHTPRSGVTAQNLAYVMYTSGSTGRPKGVLVEHRGLCNLPTVQAKLYAIAPSDRLLQF APLCFDTSFCEIALALLSGATLVMGTADELLPGPPLVELLKKHAVTAMLLAPSVLAALPEQQS AALPLRVLAMAGEACPAELVKRWKAPGRRLFNSYGPTETTIWASSAADLSDERIPPIGRPIAN TQIYVLDEALEPVPIGVPGEIFIGGVGVARGYHGRPDLTAERFVPDPFGQTKGARLYRTGDRA RWLPDGNLEFLGRNDEQVKVRGIRIELEEIRAALLKHPAVAQAVAVVREDAPGDKRLVAYVVG RGGARLTAAELRQSVSERLPATMVPSSFVALDALPLTPNGKVDRRALPEPERSAGGEDHVAPR NAIEEELTRIWADVLGAKRVGVHDNFFDLGGHSLLLVRVHDRLGQRFDRPPSMVDLFTYPTVA SLARFLGERANGKQSPREAAADVTERGRRRLEARARRAKAIRGPT SEQ ID No 28 (>ORF10) MKHNIGWLLPAALATLAFVPACSPNHGEDAPSVTSAESGAAPSADCVALGAKLQAALDGAAAA QKAPGAAAAVQSGDCVWRGATGVSDLVASTPTKPGDLFRIGSITKTFVSTLILMLRAEGRLSL DDAVSKYVKGIPAGDQMTLRQILGHTSGLFDYTYSPALGQMIEVDPTpAFAPAELIALATAEA PYFAPGAGFRYSNTNYIVAGLVAEAVSGGTLAGLLRTRILDPVGLAHTYLDGAEPPVQGLIRG YGDYGAGLVDITDQLSPTEAWAAGALVSNVDDLNRFFALLISHELLSSDELQDMTTWTPTMWP HEPGYGLGLIERDSALGSLNGHCGIIWGFQSASYGVPGRGDAITALINRSDGDAARLVDELAK VVKER. SEQ ID No 29 (>ORF11) MSIDRAVLEQLDRVGGRLAEGKALKLLEDIAWPREVEERFFAAGEDRLPEVEYRVDRDGLARR VAELRELLGAIDGDAPALGWLRDNVPAQIQAAELLEAAGTRAFSARSQELYGGARSRFFGGSL WO 00/22139 PCT/US99/23535 99 RNIDLAEHLTERLRVHGWDEASDPEEEPLDAGALRDMLAARVAGRAPRLDLEITVDPRVTAKV VAGMSRVRIRPEATFAAWEAEGLWHHEVETHALTAHNGAAQPRCAFLRSGGPRTTRTQEGLAI FAELYSRSLSIGRLTRLAERVRLVDMAEQGASFLDLYRHLRERGAERRDAYFDAQRVCRGGLV EGGAPFTKDACYLAGLLEVYAFLAAVLRGGLRDEVELLVCGRIALDDIAVLAELRAAGVLERP 5 RYLPGWLRAWQTLLPYFAFTSFMDGIDLGPVERHFQELLRVAADARPAGEGRRRRGRPREG SEQ ID No 30 (>ORF12) MSESVAQLEEHRAALTGHCYRMLGSVVDADDAVQETMVRAWRSLDKFDGRSSLRTWLYRIATN VCIDLRADRARRARPIEEGPVGTVDDALETRPRTHWLEPVPDAHALPADIDAAERAMLRQSIR 0 LAFVAALQHLPPKQRAALLLTEVLGWSAAEVADSLNTSVAAINSALQRARATLASRDLGDARP SLPEPQSALLDRYVNAFERYDVDALTALLHQDATLSMPPFTLWLRGHESIRAWLVGPGAGCRG SRLIPTAASGSPAFAQYRPAPEGGHRAWALIVLDVAGDRIVSMTSFLDTETLFPRFGLPLDLP A 5 SEQ ID No 31 (>ORF13) VTIASIDHRDQDLMTGPQAKAPAPAAPDAAPSRRAVWAGRVLSGLATLFLTFDAAVKVLKLF PAEASTAELGFPAHLVPTLGYLQIACLVAYLIPRTAVLGAILWTGYLGGAIAIHVRVENPLFS HTLFPIYVAAFLWAGLWLRDRRVPALTASPSSQGR 0 SEQ ID No 32 (>ORF14) MTTKNPRKLFVNLSVRDLKRSMEFFSKLGFEFNPQFTDEKAACMVVSEEAYVMLLVESFFKTF MKKEICSTSTHTEGLFALSCSSPAEVDDMVKKAVAAGGSHAMDPQDHGFMYGWSFYDVDGHHW EVMWMDPKAIQP SEQ ID No 33 (>ORF15) MTPSERLDATFAALADPTRRAILARLASGEASVTELAKPFAMSQPAISKHLKVLERAGLISRG RDAQRRPCRIEAKPLEDASGWLDNYRRFWEGSYERLDDLLEELKERESKGERSKR WO 00/22139 PCT/US99/23535 100 SEQ ID No 34 (>ORF16) VAPASAPAAGGRDAAPFLDEAAQWLRGEQAPASRPAGEGPAGRLPGRVLVADDNADMREYALR LLVAEGWTVEAVADGRAALERARAHPPDLVLTDVMMPRLDGFGLLPALRADDRTRGVAVVMLS ARAGEEARVDSLEAGADDFLVKPFSAKELLARVRIHVELARRRREAEGQRQYLNDLFMQAPGP 5 IAILRGPEHVFEVVNPLYQRLVGGRSLVGEPIRAALPELEGQGIWELLDAVVRTGEPIVGKEL PVRLDRRGDGTTEEVFFNFVYQPMRDRDGAVEGVFVFAFDVTDQVRARRRVEALVEALKLADQ RKDEFLAMLAHELRNPMASISLSLTLLDDADGDGPASARYREIARRQMGHLVRLVDDLLDVSR ITRGTVELRLEDVDLAAVVQSAAAAVRPAVEARRHDVSLSVGPGDFGMRADATRLEQVVTNLL TNAAKYTPPGGSISVRLTREAAVGAPEAVLRVRDTGRGIPAAMLEKVFDLFTQVDQTIDRSTG 0 GLGLGLTLVRRLLELHGGSVAAASAGPGQGSEFTVRLPLGPGAAPQPAPSAGPPPPREGPPPA QRDEPPPPPAQPAEAPEAAADRRRVLVVEDAEDVRRVMRAYIEALGHEVTVAVDGLEGVKKLL ELRPEVAFVDIGLPGIDGYEVARRARAAPGGEALYLVALSGYGGPDDQARSRRAGFDLHLTKP VVGATLQDVLTAPRT 5 9. DNA sequence according to claim 7 selected from the fol lowing (a) open reading frames, and peptide sequences corresponding to said open reading frames: pEPOcos6_ORF1 sequences: (1) nucleotide sequence Seq ID No 35 (>pEPOcos6_ORFl.seq) D GGATCACCTGCGGCGCGATCGCCGACCTCGTGCTGGTGTTCGGCTCGCTGGATGAGAAGCCGG CGGCGCTACTGATAGAGACGGCGACGCCCGGGCTGCGGGTGGAGCGGTTGCGGGAGATGCTCG GCTTTCGGGCGGCCCACCTGGCGAAGCTGTCCTTCGACGGTTGCGAGGTCCCCGAGGCTCAGC TGATTGGCCGGCCCGGCTTTGCGCTGATGTATCTGGCCCCCTACGCCCTGGATTTCGGTCGGG TCAGCGTCGCCTGGGCCTGCCTGGGCATGATCCGCGCTTGCCTGGAGACCTGCGCACAGCACA D TCCTCACCCGCCGCACCTTCGGCCACCTGCTAGCCGATCACGGCATGATCCAAACCCTGATCA WO 00/22139 PCT/US99/23535 101 CCAACCTGGGGATTCACCACCAGGCGACGCTGCTCCACACGCTGCAGGCCTGCCGCGCCAGGG ATCGCGGCGACGTGACCGCCTCCGAGGCCACCCTCGCCGCCAAATACCTCGCGTCGCGGACGG CGGTCCAGGAGACGACCAACGCGGTCCAGATCATGGGCGCGCTGGGCTGCGACGAGGAGGGCG CGATCGCCCGCCACTTCCGCGACGCCAAGACGACCGAAATCATCGAAGGCAGCAACCAGATCA TCGAGGCGCTGCTGGCCAAGAACATCGCCCGCGCCGGTCGCGACAACTATCGCCGCTTCCTCG ATGCGGAAGTCGAGCCCGGTCGGGCCGGAGGCGCACCA (2) peptide sequence Seq ID No 36 (>pEPOcos6_ORFl.pep) ITCGAIADLVLVFGSLDEKPAALLIETATPGLRVERLREMLGFRAAHLAKLSFDGCEVPEAQL IGRPGFALMYLAPYALDFGRVSVAWACLGMIRACLETCAQHILTRRTFGHLLADHGMIQTLIT NLGIHHQATLLHTLQACRARDRGDVTASEATLAAKYLASRTAVQETTNAVQIMGALGCDEEGA IARHFRDAKTTEIIEGSNQIIEALLAKNIARAGRDNYRRFLDAEVEPGRAGGAP* pEPOcos6_ORF2 sequences: (1) nucleotide sequence Seq ID No 37 (>pEPOcos6_ORF2.seq) ATGACGAGCGCGGTCCCGACGCGTCAAACCAGCCTGCTCGACGACTTCGAGCGCGTCGCCGAC GTCGATCCAGAGCGGATCGCCGTCCACGCGAGCGAGACGAGCCTGCGCTATGGCGACATGAAT GCGCGCGCCAACCGCATTGCCCACGGGCTACGGGCGCGCGGGATCGGGCCCAATCAAATCGTG GCGGTGGCGATGGCCCGCACGCCCGAGCTGATGATCGTGCTGTACGGCATCCTCAAGGCCGGC GCGGCCTACATGCCCATCGCCCGCGACGCGCCGCCGCTGCGCCGCGATCATATGCTGCGCGAG AGCCAGGCTGCTCTGATGATCGCCGACGAAGAGATCGCGGGACTCGCGGCCCGGGTGCTGACG CCGGCCGACCCGTTCTTCGCGGCCATGCCGGACCACAACCCCGAGCCGCGTCACGACCCGACC GACCTGATTTACGTCATCTACACCTCGGGCTCGACCGGCCAGCCCAAGGGCGTGGCCATGGAG CACCGCGCCGTGTGGAATCGCCTGACTTGGATGCAGGCCCAGTATCCAATCGACACGCAGGAC GTGATCCTCCAAAAGACGCCGATCGTCTTCGACGTGTCGGTCTGGGAGCTGTTCTGGTGGCCG CTGGCCGGCGCCTCGGTGGCCCTG CTGCCGCAATCCATGGAGAAGTTCCCCTGGGCGATATCG GCGACGGTGGCGCGGTGCGGGGTGACGGTGATGCATTTCGTACCATCGATGCTGATGGCCTTC WO 00/22139 PCT/US99/23535 102 CTTCAGGTGGTGGCGGGCCGGCCCGAGATGGCGGACCAGATGAAGGGCCTGCGCTACGTCTTC TGCAGCGGCGAGGCCCTGGCGCCGG 7CCACGTGTCAGCCTTTCAGGAGCACATCAACCGAGCG GGCAGCATCAGCTTGACCAACCTCTATGGACCCACCGAGGCGGCGGTCGACGTCAGCTACTTC GACTGCCCGCCCGGCGCGTCACTCGCGCGGGTGCCGATCGGACGAGCGATCACCGGCATCCAG 5 CTGCTGGTCATGCGCGACGGCGTGCCTCAGCCGCCCGGCGTCGAGGGTGAGCTCGCCATCGGC GGCGTTGGTTTGGCGCGCGGCTACATCTCACGGCCAGACCTGACCGCCGACCGGTTCGTGCCG CATCCAGGCGGCGACGGCCAGCGGC TCTACCGCACCGGCGATCTGGTGCGCAGGGACGCGGAC GGCGAGCTGGTCTTCCTGGGGCGCATCGACCATCAGGTGAAAATTCGCGGTCTGCGCATCGAG CCCGGGGAAATCGAGGCCCAGATCAGCGCCCATCCCGATGTGGCCGACTGCGCGCTGATTATC 0 GAGCAGGACTCGGAAACCCTGCCCAAGCTGACCGCCTACATTGTCGTGGCGCGACCGGGCTTG ACCCGGAAGGCGCTGCTACAGTTCCTGGGCGCGCGGCTGCCCGACTACATGCTCCCGAACCGC TTCCTGACCCTCACGGAGCTGCCCGTGACCGCCAACGGTAAGCGCGACTGGCGCGCGCTGCTC GGCCCGCTCGAGACCCTGCCTCTCCCTTTCTCC 5 (2) peptide sequence Seq ID No 38 (>pEPOcos;_ORF2.pep) MTSAVPTRQTSLLDDFERVADVDPERIAVRASETSLRYGDMNARANRIAHGLRARGIGPNQIV AVAMARTPELMIVLYGILKAGAAYMPIARDAPPLRRDHMLRESQAALMIADEEIAGLAARVLT PADPFFAAMPDHNPEPRHDPTDLITVIYTSGSTGQPKGVAMEHPAVWNRLTWMQAQYPIDTQD D VILQKTPIVFDVSVWELFWWPLAGASVALLPQSMEKFPWAISATVARCGVTVMHFVPSMLMAF LQVVAGRPEMADQMKGLRYVFCSGEALAPAHVSAFQEHINPAGSISLTNLYGPTEAAVDVSYF DCPPGASLARVPIGPAITGIQLLVMRDGVPQPPGVEGELAIGGVGLARGYISRPDLTADRFVP HPGGDGQRLYRTGDLVRRDADGELVFLGRIDHQVKIRGLRIEPGEIEAQISAHPDVADCALII EQDSETLPKLTAYIVVARPGLTRKAkLLQFLGARLPDYMLPNRFLTLTELPVTANGKRDWRALL GPLETLPLPFS WO 00/22139 PCT/US99/23535 103 pEPOcos6_ORF3 sequences: (1) nucleotide sequence Seq ID No 39 (>pEPOcos6_ORF3.seq) 5 ATGTTACACCCGATTCCCACCGACCGTTTCGCCCTGAGCCGACCGCTCTTTCGCGGGTACCTC GCGCACGATCCGATCGTGCAGGGCGTGCTGGCGGGCGACCATCCAGGCTGGGTCCTGGTGGAC CGCGAGCCCGAGCCGCGCACGGCGCTGCTGTGGGCCTTTTCCGATCGGCTCTTCTGCGTGGGC GCAGCTGACACGCTGACCCCGCACGCGCTGGCCGAGCTGTTCCACGACCGACTGATCCCCCAG GCCCGTAAGATCGGGCAGCCGTTTTTCCAGGTTCAGGGCGAGACGGTCGACACCTGGTCGGAC 0 CACCTGCATCAGGTGTCGCCGCACGCGACAGTCTCCTTCCGCCAGGCATTCCGCTTCGACCGC GACCTCTTCGAGCGGCTGCCAACCAAGCCGGAGCTGGCAGAGGCGCGGCTCGTGCCAATCGAC GCGCGGCTGCTGGCCGAACAGGCTGATCTGCGCGAGCGGATACTGGCCTCCTGGTCCAGCGAA GCTGCCTTCCATGCGCGCGGTTTCGGCTTCTGCTACCGCGTAGGTGACCAGCTGCCGAGCGTG TGCCTGGCATCGCACGTAGGCGGCGGCGCGGCCGAGCTGAGCATCAACACCGAGCTCGAAGCG 5 CGCAATCGAGGTATGGCAACGCGGCTGTGCCGGCGTTTCATCGCCGAATCGCTGCAGCGCGGC CTGACGCCTTGCTGGGGCACCGAGACCTTTCGCCTGCCGTCAATCGCGCTGGCCCAGAAGCTC GGTTTCATCCCGACCTTCACCTTCCCCACCTACTGCTTCGCGACCGGCACCGAACAGCCGGAC GACAACTTCCTAGGCGAGCTGTACTACAGGGAATCGCGCATCGCCGGAAGTGGGACCGATGAG CCGCAAGCGGTTCGGCTGGCGCGGGGTTGGAGCCTGGCCGGCGACACCGAGCGTGCCGCGAGC 0 TTCGCCGCACGCGCCCTGGCCGAAGGGTGGGCCGGCCACTCGACTCTGGCCACCGATCCGGAT TTCGCCCGATTGCGCGCCAGCGCCGCCTGGCCCCGCCTCAATGTCCCT (2) peptide sequence Seq ID No 40 (>pEPOcos6_ORF3.pep) 5 MLHPIPTDRFALSRPLFRGYLAHDPIVQGVLAGDHPGWVLVDREPEPRTALLWAFSDRLFCVG AADTLTPHALAELFHDRLIPQARK7GQPFFQVQGETVDTWSDHLHQVSPHATVSFRQAFRFDR DLFERLPTKPELAEARLVPIDARLLAEQADLRERILASWSSEAAFHARGFGFCYRVGDQLPSV CLASHVGGGAAELSINTELEARNR3MATRLCRRFIAESLQRGLTPCWGTETFRLPSIALAQKL GFl PTFTFPTYCFATGTEQPDDNFLGELYYRESRIAGSGTDEPQAVRLARGWSLAGDTERAAS 0 FAARALAEGWAGHSTLATDPDFARLRASAAWPRLNVP WO 00/22139 PCT/US99/23535 104 pEPOcos6_ORF4 sequences: (1) nucleotide sequence 5 Seq ID No 41 (>pEPOcos6_ORF4.seq) ATGATTTGTCACTCCCACCGCTTCATTTTCCTCCACGTTCCCAAGGTCGCCGGCACAAGCGTC AAGGACGTCCTCGGCCAAGAGCTATTCCAGGAGGACCAGGTCACGTTCCAGATCGCTCCCAAT CCCCACTACCCACCTGAATGGACTGCGCCTTACGAGGAGCACATTATTGCCGCTGAATTGAAG AGCCAGTTGGCGCCGGAAATTTGGGACGATTACTTCAAGTTCGCCTTCGTGCGCCATCCGCTC D GACTGGGCGGTCTCCAATTACTTCTTCTTCCTGCGCGACCGCAA-AGGCCATCCGGCCCACGAA TTCCTGGAGCGGAAGGGCTTCGCCGGTACCATGGACATGTTTTTCGGAGCGGCCGGGCGCCAT CCGCTGGTCGCCGGCATGCGCTTCAGCCAATGGGAGTTCTTGTGCGACAGCGAGGGCCGGACG CTGGTGGACTTCGTTGGCAAGTACGAGCGGCTCGAGCAGGACTTCGCCGCCGTGTGTATCCGC ATCGGGCTGACCCCGCCCGACTTGCCGTGCCTCAACCAGACTCGCCACCAATCCTTTACCAGT D TACTACGACGAGGCTTTGATGCGCCAAGTCAGCCGCGCGTTAGCTCGCGATTTCGAAATTTTT GATTATGCC (2) peptide sequence Seq ID No 42 (>pEPOcos6 ORF4.pep) D MICHSHRFIFLHVPKVAGTSVKDVLGQELFQEDQVTFQIAPNPHYPPEWTAPYEEHIIAAELK SQLAPEIWDDYFKFAFVRHPLDWAVSNYFFFLRDRKGHPAHEFLERKGFAGTMDMFFGAAGRH PLVAGMRFSQWEFLCDSEGRTLVDFVGKYERLEQDFAAVCIRIGLTPPDLPCLNQTRHQSFTS YYDEALMRQVSRALARDFEIFDYA 5 pEPOcos6_ORF5 sequences: (1) nucleotide sequence Seq ID No 43 (>pEPOcos6_ORF5.seq) ATGAAAGTGGACAAGCGGAATGTCGACGACATTCTCGGACTCACTCCGACACAGACAGGCATC D TTGTACCACTACCTGCTGGACCCGCAGGCCGACGCCTATTTCGAACAATTGACGCTGCACCTG WO 00/22139 PCT/US99/23535 105 GAGGGGCCGCTCGACGTAGCGCGC-TTCCGCCGCGCCTGGGAGCGCGTGGTGGCGGCTCACGAC CAGCTGCGCGCCGTGTTTCGCTGGCAGGGATCGAJCACCCGGTGCAGATCATCCTCAAGCAG CACGTGCCGGACCTGGAGTTGGCGGAGGTCCCGCGCGACGCCGATCCGGCAGCCTTCCTGGCG CAATGGGTCGCGGCCGACCGGGCGCGCAAGTTCGACTTCGAGACGGTGCCCTTTCGCATCGGC DCTCTGCCGGACTGATACCCAACATCACGTGATGCTGCTCAGCAATCACCATATCCTGATGGAC GGTTGGAGTACGGGCCTGATTCTGCGGGACTTCCTCGCCTGCTACGGCGACTCCGAACTGG CGGCCACGCACCCGACGCACTTCAAGGCGTTCATCAAGTGGCACCAGACCGGCCACGCCGG GGCGAGGAGCGATTTTGCCGCGAC C TGTTGCGCGATGCGCCCGACGGCGGCTTTCCCCCCCTG GGCGTCGAAGAAGGCACCCGCCAC-TCGCTTGACTTCGGCGCCCGCAGCCGCGCTCTCGACGAC CGCTTGACCCAAGGCTTGCGCGACATGGCTCGCGACCTCGACGTCACCCTCGCCGCGATGCTC CATACCGCTTGGGGCCTTCTACTC CAGCGCTACCAGAACAGCTGCGAAGTGATATTCGGGACC ACCGTTTCCGGCCGCAACGTCGAG-CTCGCCGGCCTCGACGAGGTGGTCGGCTTGTTCATCAAC ACGATTCCGTTCCGCTTCTCGGCCGCGGCCGCGACGACGCCCGTCGAGGCCTTCCGTGCGGTA CAGCGCAATCTGCTGGCGAGAAGCGAGTTCGAAGCCACCCCGCTGGTGGACATCAAGGGCTGG DAGTGGTCTCGGTCCGGGCGCGGAACTGTTCGACACCATCCTGGTCATCGAGAACTATCCCTTG GACCGCGCTATCTTCGAGAGTGATTCCAGCCTGCGGTTGACCGACCACAXATCTTCGAGCGC ACCAATTACGGGCTGACCCTGACCATCGAGACCTTCAGCCGGTTGCACGTGACGCTAGCCCAT CGCCGTGACCTGCTGGGCGACGCG-GCCGCTGAGCGAATGCTAGATCATTTCACCGGCCTGCTC CAAGCCATLGCTGCGCTTCCCTCACAGCCTTCGCGCGCCTCGAGATGAAGCGAACACGAG DCC' -CACCGCGTCCTGCACCACTCAACCAACGCGTCAGCCGCTGCCGTCCCATCGGCTTTC CACCAGTTGTTCTTCGAGCAGGCCCAGGCCGATGGGGCACGACCGGCGCTGTGGTGCGGCGCC ACGCGCTGGACCTACGGCCAGCTG :CTGGAACGTGCCCTGCGTC-TGGCGGGACGGCTGCAGGA GCCGGCTTC -GCCCGAGGCGATGTCGCCGCCGTCAGCCTCGGCCCGGTTCCGGATCTGATTCCC GGT TTGCTGGGCCCGCTGTTCGCCGGCGGCGCCTACCTGCCGCTCGATCCCACCCTGCCGGCC CAGCGCTCGCGGTTCATCCTCGACGATGCCGGTTGCCGCTTCCTGATCAGCGACGCGCCACTC GCGGGGCCCACGCCGATCCATCCGGACCCTGCCGGCGCCAGCCCCGTTGACGTCATTTTTCC TGTCAGGACGGCGCCGCGCAGCC.CGCCTACCTGATCTACACCTCGGGCTCCACCGGCCAGCCC AAGGCGTC-TGGGTTAGCCACCGC-AACCTGATCAACTTCCTGACGGGCATGAGCGCAATCCTG C CGTCGCGOGCCGACGACGTGTZ--CCTCTCGCTGACTACCGTGTCGTTCGACATTTTCGGGCTC G.DAACGTCGTTCCCGCTCAGCCGCG GCTGCACGATCGTCTTGGGCACGCGCGCCGAGCAGTTG WO 00/22139 PCT/US99/23535 106 GACCCGGCCGCGGCTGCCAAGGCCATCTCCTGCCATGGCGTCACGGTTTACCAGGCGACGCCA TCGCGACTCCAACTTCAACTGGAGCACCCCACATTTGTCCGCGCCATCGGCTCCCTGACGACC CTGCTGGTAGGCGGCGAACCCCTCCCAGCCGAGCTGCTGCGGCGCGTACGCGAAGTGACCGAT GCGCGTATCTTCAACCTCTACGGTCCCACCGAAACCACCATCTGGTCCACAGCCGGGGAGGTC 5 ACCGCGGCGGACGTCCCGGATATCGGCCGCCCGATCGCAAATACCGGCGTTTTCCTTCTGGCG CGAGACGGCTCGATCCAGCCGCCGGGCCTGGTGGGCGAGTTGTGCATCGCCGGCGAGGGCGTG GCGTTGGGCTACCACCGACGGCCGGACCTGAACCGAGAACGGTTTCGCGAGATTCCGCCGGGC CGCCTGCCCTTTGCCGGCAAGCTCTACCACACCGGCGACCTGGCCCGCTGGACCGAAGACGGA CGGCTCCTCTGCCTGGGCCGTCTGGACGACCAGCTCAAAGTGCGCGGCCATCGCGTCGAGCCG D GGCGAGATCGAGGCAGTGATGGCGCGCCACCCGGCGGTCACGCAGGCGGTGGTCGTCACGCGG CCGCGCAACGGCGAGCCGGTCTTGGTCGGGTTCTGGACTGCGGAAGGTGAGCCGATGCCAGAG GAAGCGCTGAGCGCTTACCTGGCCGACCGACTGCCGAGCTACATGGTACCCGAACGGTGCATC CTCATGAAGGCCATGCCGCTAACCGGCAACGGCAAGATCGACCGGCGCGCCCTACCCAATCCC TTCGCCTTGACCGAGTCGACCCGGCAGGCGGCGCCGCGCACCTTGGCCCGCACCGCCGGCGAG CATCGGGTTGCCGAGCTGTGGCAGGCCTTGTTGCGACGCGAGGCGATCGGCTTGGACGAACCC TTTTTTCAGGCCGGCGGGAACTCATTCGGCTTGATTCGGCTTCACGCCAAGCTGGAATCCGCC TTCGGGAAGTCGTTCCCGATCACCGATTTGTTCCAGCATACCAGTATTCGCAGCCAGGCAGAA ATGCTGAGCGGCTCGTCCGTCGAGGCGCCGCTCGCGGGAGCCGTGCCGCAACCCCCGGCCGCC GCCGCCCAAGTTGCCTCCTCGGCAGCTAAATCCCCAGGGGAGCGCGGCGCGGCAGCGACGTCG 3 AGCGGCCTGACCGCGCAACCGCCCCAACCCCACTTCCGGCCCATCGCCGTTATCGGCCTCGCC GGCCGATTCCCCGCCGCACCCGACCTCGACGCCTTCCTTGAACTGCTCACGGAGGGTCGCTGC GGCATTCGCTTCTTCAGCCAAGCCGAGCTGCGCGACGAGGGTCTCGACGCGAATCGAATCGCG TGTCATAACTATGTCCCGGCCAAAGGTTTCCTCGACCGGGCCGACCACTTTGATGCCGACTTC TTCGGCATCCCGCCGCGCGACGCAGAAATCACCGATCCGCAAATTCGGCTTCTGCTTGAGTGC TGCTGGAACGCGCTGGAGCATGCCGGCTACCCGCCCGGCGGCGGCGAGATCGGGCTCTTCGCC GGCTCCTCGGCCAACTATCACTGGCTCGAATACGTGGGCATTTCCGAGGAGAGCAGCAATCGA TTCGCCGTCATGATTCAAAACGAAAAGGACTACCTGGCCACGCGGATCGCCTACCAGCTCGAT TTGAAGGGCATTGCCGTCACCGTGCAAACGGCCTGCTCGTCGTCGCTGACCGCGGTCGAGCTG GCCTGCGATGCGTTACACGCCGGCCGCGTGACCATGGCTTTGGCTGGTGGCGTTGGTCTGACC D TATCCGTTGCGCGCCGGATACCTGCACGAGGATGGAATGATCTTCTCCCCCGACGGTCGGTGC WO 00/22139 PCT/US99/23535 107 CGGGCCTTCGACGCCCAGGCGGCCGGCACGGTCTGCGGCAACGGTCTGGGCATGGTGGTGCTG AAACAGCTCGACGCGGCGCTGGCCGACGGCGATGCCATCCACGCTGTGATTAAGGGCATCGCG GCCAACAACGACGGCGCGGCCAAGATCGGCTACACGGCGCCCTCGCAGAACGGTCAGGCGCGG GTGATCCGCGCCGCCCATAGGCTCGCCCAAGTCGCGCCGGAGACCATCGGCTATGTAGAAGCC 5 CACGGTTCGGGCACGCCGCTGGGCGATCCGATCGAGGTGGCGGGCCTGACCGAGGCCTTTGAC AGCCCGCGTCGCGGCTTCTGCGCCTTGGGTTCGGTCAAGTCGAATGTGGGTCATTTGGATGCG GCAGCGGGCATCGCGGGTTTCATCAAGGCGGTGCTCTCGCTGTCCCATCGGACCCTGTTCGCC AGCCTCCACGTCGACACGCCCAACCCGCAGATCCCGTTCGCCGACGGTCCGTTCCAGGTCAAC ACGGAGACCCGGCCCTGGCCAGCTGCCGACCATCCCCGCCGCGCCGGCGTCAGCTCCTTCGGC 0 ATCGGCGGCACCAACGTGCACGCCGTCCTGGAAGAGGCGCCGCAGTTGGCCGAGCACGCGGGG CGGCGGCGCGAGCGGCAGCTGTTCCTGGTCTCGGCGCGGACTGCAGCCGATCTGGAGCGACGC ACCGCGGCGCTGGTCCGCCACCTGGCCGCGCATCCGGACCTCGCACCAGATGACGTTGCCTTT ACCTTGCACGCGGGCCGCAAACCGATGACCCACCGTCGTTTCCTGGTCGCCGCCGACCTCGCG GAAGCCGCCGCGCGTCTGGCCGAGCCCGATCCAGTCAAATCCGCCGCGGCGCGCGCCGACCGC 5 TGCCAGGTCTGGATGTTCGCCGGTCTCGGCTCTCAATACCCCGGCATGTGTGGCGGCCTCTAT CGCACCGAGCCGGCCTTTCGCGAGCAAGTCGACCGCTGTTTCGACCTCCTCGCGCCGCGTTGC GATTTGAAGCCCTCGCTCTTCCCCGAGCCCGATCAGGCCATCGACGCATCAGCCCTCGCGGCC ATCGACACCGCCCAGATCGCCGTCTTCGTCTGCGAATACGCGCTCGCACGGATGCTGGAAGGC TGGGGGCTGCGTCCGGATCGGCTGATCGGTTACAGTTTCGGCGAATACGTGGCCGCCTGCCTG 0 GCCGGCGTCTTCTCCCTGCCCGACGCCTTGGCAATCGTCCGCGAGCGTGGCCGGATCCTGGCG GCGGCCGAGCCGGGCGCGATGGTCAGCGTGCCCCTTCCGGCCGAGCGCGTCGCGTCGCTGCTG GAGCCGCCGCTTGCCTTGGCCATTGACAACGGCCCCTCATGCGTGGTGTCCGGGCCGGTCGAA CCGGTGCGCACCTTCACCGCTCGCATGAAGCGGGACCGGGTCTGGGTGACGCCGCTCCAGGCC GAGCGCCCGATGCATTCGCCGCTGATGGCCGAGGCCGGCGGCTCACTGCGCGCCATGTTGGCC 5 GGGTTCCGCCTGAATGCGCCGCGAATCCCGATCTTAAGCAATGTTACAGGAACCTACCTAACC GACGAGCAGGCCCGAGACCCCGATTACTGGGCCCGTCACCTGTGCGGCAACGTTCGCTTCGCC GACGGTGTGCGAACCTTGTTGGC CGAGCGCGATCCGGTGTTCCTTGAATTCGGGCCGGGCCGC GATCTGAGCTCCTTGGTGCGCCACCAGATGCCGGAAGGCGCCGACGAGCCGATCGCACTGATC CGTCATCGCGAAGATCCGGTGCGCGACGAAGACCTCCTGCTCGATGGCTTGGGCCGCTGCTTC 0 CTGCGTGGGGCGACCCTCCACGGGCAGGCCTTGTACGCCGGCCGAGGCTGCCGCCGCGTGCCG WO 00/22139 PCT/US99/23535 108 CTGCCCGGTTACCCGTTCCA GGGTCC -ACGCTGCATGCCGGCCCGCGCCGGACTGCCCGGCCTG GCGCGACCGACCGTGGGAGCGACCAC CATCAGCTACCGACCAGCCTGGAAGCGGGCGCCGCGC TTGGCGGCTGTCGAATCCCTCGCGC-CGCAATCCTGGTTGGTATTCAGCGACGGCAGCGAATTG GCGGGCGAGCTGGTGGCCGGCCTGCGCGCTTCCGGTTGCGCGACCACCCTCGTCGAAGGTGGG 5 CTGGCGTTCGCGCGCTTCGCGGGC3,-CTTCCGCGCGAAJTCCCCGCGAGGXJACAGATCTCGCA CAGCTGTTCGCGACCCTGTCGGCCGAAGCGATGCTGCCCACCCACATCCTGCACCTGCTCAGC CTGCCGTCGCCGGAGCGCGACTCCCGCTGGCGCGCCTGGAGCACCTCACCGAGCTGGGCTTC CACCATCTGCTGGCCCTGGCCCGCCAACTGGAGGCGGTCGGCGCCCCCGAGGTCCGCCTCGCC GTGGTGACAACCGGCCTGGCGGCGAzTTGGCGGCGAGTCCGAGCTGCGGCCCGAGGTCGGGCTG 0 TTGCGGGGACCTGTCCGCGTGATTC2CCTTTGAJATTCCCGAACTTGCGGCTGCGCCTGATCGAC CTCGACTCGGCCGATCCCATCTGGCTAGCGGTTGTGAGCCGTTGCTGCGCGATGGGCGCT GCCCCGGGACCTGAAGAAATCGCC-CTGCGCGGCACCAGCCGTTGGGAGTTGGGCTACGAGCCG GTCGAGGGGGGCACCGTGAGCACCATCTCCTCGCGACTGCGCGAGGGCGGCGTCTATCTGATC ACCGGTGGCCTCGGCGGCCTGGGT CTGGCCTTGGCCCGTCACCTCGCCCGGAAGTACCGCGCC 5ACCCTGATCCTCGCTGGCCGGCGAGG7(-CGCGCCGGCGCGCGAGCTCTGGCACCAGGCGCCAGCG GAGTTCGTACCGGTCGCAGCTGCGATCGCACAGATGGAGGAGTGTGGCGCCCGCGTGATTCCC GTCGCGCTCGACGTCACCGACGCCGACCAAGTGAACGCGTTGTTCGCCACCATAGAAGCTACG GTCGGCAAGATTGAAGGCGTTTTC C-ACATGGCTGGCATCGTTGACGGCGGCATCATTCGAACG CGCACGCGCGCTGCCAGCGACGCCGTGCTGGCGCCCAAAACGGTCGGAAC CTGGATTCTCGAT 0 CGGGCTCTCCGCGGCGCCGGTGG' CCGCTTCCTGGTGCTGTACTCCTCGATCAACGCGGTCGTC GCGCCCTTCGGCCAGGTTGCCTACGCCGCCGCCAACGCCTTCCTCGACGCCTTCGCCAGCGCC CACGAACACGACGAGCGTCTTTTCCG%-CGTCAGCATCGGTTGGGACACCTGGCGCGAGGCCGGC ATGGCCGTCGATGCCGCCCGCGCC3-GCGGCGACCAGGCCCCGCTCGAAGGGCTTAGCGACGAG CAGGGCTTGCGCCTGCTCGAAAGC-GCCTTGGTCGGTTGCGAACCGCGACTCCTCGTCTCCATC 5AGCGAACTGCGCGCTCGACTAGCCG- AGCATCATCGCAACGGCGGCATTCCCCGGTTGCTCGGG CCCCGCGCCAACGAGGCGGGTGCAGOCTGATTCCGGCGAGGAGGGCGCCACGCAAGACGCGTCG CCGGCCCGTCGCGCCCGTCCCGAT-CTGGTCGTGGCCTTCGCGCCGGCCGGCAACGAGCTGGAG CGCCGGATCGTGGCCATCATCGGCGC"-CTACCTGCGGCTCGGTCAGGTGGGCGTCGACGACAAC TTCAACGATTTGGGCGCCACCTCC:CTCGACCTCATCCAGATCGCCCAACGCCTCGGTCGCGAG 0 TTGGGCCGCGATGTCCCTGTCGTCT-CGCTCTACCAACACCGCACCGTACGCGGGCTGAGCCGC WO 00/22139 PCT/US99/23535 109 TTCCTCGGCGGCGCGCTCCAATCCGCGCGGTCCGGCGTCCCGACGGGCGCTGCCGCACCGGGC GCCGCCACGCCGGGGGTTGCCACCCCGCCGCGGCCACAACCGTCGCGCCAGCACCTGGAAAAA CGCCGTCAATTGAGGAAAAAAGGGGGGCCTTCCCATCATGAG 5 (2) peptide sequence Seq ID No 44 (>pEPOcos6_ORF5.pep) MKVDKRNVDDILGLTPTQTGILYHYLLDPQADAYFEQLTLHLEGPLDVARFRRAWERVVAAHD QLRAVFRWQGIEHPVQIILKQHVPDLELAEVPRDADPAAFLAQWVAADRARKFDFETVPFRIG LCRTDTQHHVMLLSNHHILMDGWSTGLILRDFLACYGDSENWRPRTRTHFKAFIKWHQNRPRR 0 GEERFWRDLLRDAPDGGFPRLGVEEGTRHSLDFGARSPALDDRLTQGLRDMARDLDVTLAAML HTAWGLLLQRYQNSCEVIFGTTVSGRNVELAGLDEVVGLFINTIPFRFSAAAATTPVEAFRAV QRNLLARSEFEATPLVDIKGWSGLGPGAELFDTILVIENYPLDRAIFESDSSLRLTDHQIFER TNYGLTLTIETFSRLHVTLAHRRDLLGDAAAERMLDHFTGLLQAMLRFPHQPFARLEMKSEHE AHRVLHQLNQTRQPLPSQSAFHQLFFEQAQADGARPALWCGATRWTYGQLLERALRLAGRLQE 5 AGFARGDVAAVSLGPVPDLIPGLLGPLFAGGAYLPLDPTLPAQRSRFILDDAGCRFLISDAPL AGPTPIHPDPAGASPVDVIFACQDGAAQPAYLIYTSGSTGQPKGVWVSHRNLINFLTGMSAIL PVAADDVFLSLTTVSFDIFGLETWFPLSRGCTIVLGTRAEQLDPAAAAKAISCHGVTVYQATP SRLQLQLEHPTFVRAIGSLTTLLVGGEPLPAELLRRVREVTDARIFNLYGPTETTIWSTAGEV TAADVPDIGRPIANTGVFLLARDGSIQPPGLVGELCIAGEGVALGYHRRPDLNRERFREIPPG 0 RLPFAGKLYHTGDLARWTEDGRLLCLGRLDDQLKVRGHRVEPGEIEAVMARHPAVTQAVVVTR PRNGEPVLVGFWTAEGEPMPEEALSAYLADRLPSYMVPERCILMKAMPLTGNGKIDRRALPNP FALTESTRQAAPRTLARTAGEHRVAELWQALLRREAIGLDEPFFQAGGNSFGLIRLHAKLESA FGKSFPITDLFQHTSIRSQAEMLSGSSVEAPLAGAVPQPPAAAAQVASSAAKSPGERGAAATS SGLTAQPPQPHFRPIAVIGLAGRFPAAPDLDAFLELLTEGRCGIRFFSQAELRDEGLDANRIA 5 CHNYVPAKGFLDRADHFDADFFGIPPRDAEITDPQIRLLLECCWNALEHAGYPPGGGEIGLFA GSSANYHWLEYVGISEESSNRFAVMIQNEKDYLATRIAYQLDLKGIAVTVQTACSSSLTAVEL ACDALHAGRVTMALAGGVGLTYPLRAGYLHEDGMIFSPDGRCRAFDAQAAGTVCGNGLGMVVL KQLDAALADGDAIHAVIKGIAANNTDGAAKIGYTAPSQNGQARVIPAAHRLAQVAPETIGYVEA HGSGTPLGDPIEVAGLTEAFDSPRRGFCALGSVKSNVGHLDAAAGIAGFIKAVLSLSHRTLFA 0 SL:VCDTPNPQIPFADGPFQVNTETRPWPAADHPRRAGVSSFGIGGTNVHAVLEEAPQLAEHAG WO 00/22139 PCT/US99/23535 110 RRRERQLFLVSARTAADLERRTAALVRHLAAHPDLAPDDVAFTLHAGRKPMTHRRFLVAADLA EAAARLAEPDPVKSAAARADRCQVWMFAGLGSQYPGMCGGLYRTEPAFREQVDRCFDLLAPRC DLKPSLFPEPDQAIDASALAAIDTAQIAVFVCEYALARMLEGWGLRPDRLIGYSFGEYVAACL AGVFSLPDALAIVRERGRILAAAEPGAMVSVPLPAERVASLLEPPLALAIDNGPSCVVSGPVE 5 PVRTFTARMKRDRVWVTPLQAERPMHSPLMAEAGGSLRAMLAGFRLNAPRIPILSNVTGTYLT DEQARDPDYWARHLCGNVRFADGVRTLLAERDPVFLEFGPGRDLSSLVRHQMPEGADEPIALI RHREDPVRDEDLLLDGLGRCFLRGATLHGQALYAGRGCRRVPLPGYPFQGPRCMPARAGLPGL ARPTVGATTISYRPAWKRAPRLAAVESLAPQSWLVFSDGSELAGELVAGLRASGCATTLVEGG LAFARFAGGFRANPREEQDLAQLFATLSAEAMLPTHILHLLSLPSPERDSPLARLEHLTELGF 0 HHLLALARQLEAVGAPEVRLAVVTTGLAAIGGESELRPEVGLLRGPVRVIPFEFPNLRLRLID LDSADPIWRSGCEPLLREMGAAPGPEEIALRGTSRWELGYEPVEGGTVSTISSRLREGGVYLI TGGLGGLGLALARHLARKYRATLILAGRRGAPARELWHQAPAEFVPVAAAIAQMEECGARVIP VALDVTDADQVNALFATIEATVGKIEGVFHMAGIVDGGIIRTRTRAASDAVLAPKTVGTWILD RALRGAGGRFLVLYSSINAVVAPFGQVAYAAANAFLDAFASAHEHDERLFRVSIGWDTWREAG 5 MAVDAARARGDQAPLEGLSDEQGLRLLESALVGCEPRLLVSISELRARLAEHHRNGGIPRLLG PRANEAGAADSGEEGATQDASPARRARPDLVVAFAPAGNELERRIVAIIGAYLRLGQVGVDDN FNDLGATSLDLIQIAQRLGRELGRDVPVVSLYQHRTVRGLSRFLGGALQSARSGVPTGAAAPG AATPGVATPPRPQPSRQHLEKRRQLRKKGGPSHHE 0 pEPOcos6_ORF6 sequences: (1) nucleotide sequence Seq ID No 45 (>pEPOcos6_ORF6.seq) ATGAGTGAAGTATCCATTCGCCCCGGCTTGGACATCGCGGTCATCGGCATGGCCTGCCGCTTT 5 CCCGGTGCCCGCAACCTCGCCGAGTATTGGGCCAACCTGATCGAAGGCCTCGAAACGCTCAGC TTCTTCAGCGAAGAGGAGCTGCGTGAGGCCGGCTGCGATCCGCTCCAACTGGCCCAGCACAAC TACGTGCGCACCAAGGGCCTGCTCCCTGACGCAGACCGTTTCGACGCCGATTTTTTTGGTTAT TCCCCGCGCGAAGCCCAGGTGATGGACCCCCAGATCCGCGTCTTCCACGAGGTCTGTTGGCAG GCGCTGGAGCACGCGGGCTACAACCCGCATCGCCACACCGGCACGATCGGCCTGTTCGCCGGC 0 GCCGCGCCCAACGTTTTTTGGGAGTTTCTCTCCTATCGGTCCGATGCCGCCAATTTAGGCAAC WO 00/22139 PCT/US99/23535 111 TTCACGCTGGGCCTGCACAACAACAAGGACTACCTGAGCTCGCGCATCGCCTACAACTTCAAC CTGACAGGGCCCAGCTACACCCTGTTCACCGCCTGCTCGACCTCGATGGTCGCCATCCACCAG GCCGTCCAGGCGCTGCTCAACGGCGAATGCGACCTGTGCATGGCCGGCTCGGTCTCCATTACG CTGCCACTGGTTGCCGGCTACACCTACACGCCGGGCATGATCGTCTCGCCCGACGGCCATTGC 5 CGCACCTTCGACGCAGGCGCCAATGGCACTGTCTACGGCGACGGGGCCGGCGTGGTCGTTCTC AAGCGGGCCGAGGATGCGTTGGCCGACGGCGACCACATATTTGCGCTCATCAAGGGCTCGGCG CTCAACAACGATGGCAGTCGCAAGACCGGCTACACCGCGCCCAGCGTGCAGGGGCAGGTGGAG GTGATCCGCGCGGCGATGAACCTGGCGGAGGTCGAGCCGGAGGCGATCAGCTACGTGGAAACC CACGGGACGGGCACCACGGTGGGCGATCCGCTGGAGTTCGAGGCGCTAAAGGAGGCCTTCGGA 0 GGTGGCTGCAAGGCCTTCTGTGGATTGGGTTCGGTCAAGCCGAACATCGGCCATCTGGACGTG ACGTCGGGGATCGCGAGCTTCATCAAGCTGGTCCTGGCGCTGGAGCACCGCATCCTACCGCCC ACGCTCCACTTCCAACTGCCCAACCCGAAGATGGATGTGGTCGATAGCCCCTTCTACATCGTG GCTGAGCGCGAACCCTGGCGCGAAGATCTGCTGCCGCGTCGGGCCGGTGTCAGCGCGTTCGGT CTGGGTGGCACCAACGTCCACATGATTTTGGAGGAGTTTCAGCGCGAACCGGCGGCGAACAGC 5 GCGCGCACGCGCCACCTGACGGTGCTGACGGCGCGGTCGCCGCAAGCCCTGGCGCAGCTGGCG GCCAACCTCGCCGAACACCTGCGCGAACACCCCGAGTTGGCGCTGGCCGATGTGGCCCATACG CTGCTGCACGGCCGCAAGCCACATCCATTCGCGCGCATCCTGGTGGCGACCGATACGACGGCG GCGATCGACGCCTTGATGAACGACCGCGATCCGCGAACGCGTTTCTTCGAAGCGACCGGGCGC GGCGAGTCGGTGATCCTGTGTTTTGACGAAACGCCGCCGGAGCCGCGAAGCGCCCGCTACCTC 0 TGGGATCACGAGCCGCTTTATCGCGCGGCGGCGACGTCGTGCTTGGCTGGTGAGGTCGCCGAC CCGGATCTGGAAGGCTGCTTTACTGCCCTGATCGCCGAGCAGGGCGCGGCAGCCGCCTTTTGC CACCAATACGCGCTGGCCGGATGGCTGCTGGCCATGGGGTTGACCCCGTCGGCGTTGATCGGC GTGGGCCAGGGCGAGTGGGTAGCAGCGGCGCTCGCGGAGGTGTTCCCGCCATCGGCCTGCTTG CGCTGGATTAGGTTCGGCGAACGGCTCCCGCAGCCGCGCGATCAACGGATTCCGTTTCTCTCC 5 AATTTCTCTGGAAACTGGATCGTTGGGCGTGAGTTGGCCGACCCGGATTACCCCAGAAAGCAG AAGGGTAAGCGCTGCATGAAGCGCCGTCGGTCCCAACCTCGGTCAGCTGGTGCAGGATGGGGG CGATGGAACCGGCTCGGTCAGCTCGTCGCGCGCTGCTCTTCCGCGGGAAGCGGAGGCGGGACG GTGATCGGCCCGAGGGCGAGGTTCATCTCGTCGTCGACGAGCCGGGCGCGGGTGCGCGCCCAG TACCTGGGGGCGAGCTCGAGG 0 WO 00/22139 PCT/US99/23535 112 (2) peptide sequence Seq ID No 46 (>pEPOcos6_ORF6.pep) MACRFPGARNLAEYWANLIEGLETLSFFSEEELREAGCDPVQLAQHNYVRTKGLLPDADRFDA DFFGYSPREAQVMDPQIRVFHEVCWQALEHAGYNPHRHTGTIGLFAGAAPNVFWEFLSYRSDA 5 ANLGNFTLGLHNNKDYLSSRIAYNFNLTGPSYTLFTACSTSMVAIHQAVQALLNGECDLCMAG SVSITLPLVAGYTYTPGMIVSPDGHCRTFDAGANGTVYGDGAGVVVLKRAEDALADGDHIFAL IKGSALNNDGSRKTGYTAPSVQGQVEVIRAAMNLAEVEPEAISYVETHGTGTTVGDPLEFEAL KEAFGGGCKAFCGLGSVKPNIGHLDVTSGIASFIKLVLALEHRILPPTLHFQLPNPKMDVVDS PFYIVAEREPWREDLLPRRAGVSAFGLGGTNVHMILEEFQREPAANSARTRHLTVLTARSPQA 0 LAQLAANLAEHLREHPELALADVAHTLLHGRKPHPFARILVATDTTAAIDALMNDRDPRTRFF EATGRGESVILCFDETPPEPRSARYLWDHEPLYRAAATSCLAGEVADPDLEGCFTALIAEQGA AAAFCHQYALAGWLLAMGLTPSALI GVGQGEWVAAALAEVFPPSACLRWIRFGERLPQPRDQR IPFLSNFSGNWIVGRELADPDYPRKQKGKRCMKRRRSQPRSAGAGWGRWNRLGQLVARCSSAG SGGGTVIGPRARFISSSTSRARVRAQYLGASSR 5 pEPOcos6_ORF7 sequences: (1) nucleotide sequence Seq ID No 47 (>pEPOcos6_ORF7.seq) 0 ATGGAACCGGCTCGGTCAGCTCGTCGCGCGCTGCTCTTCCGCGGGAAGCGGAGGCGGGACGGT GATCGGCCCGAGGGCGAGGTTCAT CTCGTCGTCGACGAGCCGGGCGCGGGTGCGCGCCCAGTA CCTGGGGGCGAGCTCGAGGTAGCGGTCCCGCGGCCAGTAGGGCATCGCGCGAATGACGTCGGC CAGGTAGGCCTCCGGGTCGAGCCCGTGCAGCTTGCAGCTCGCCACGAGCGAGAAGAGGTTGGC CGCGGCGGAGGCGTGGTCGTCGCTGCCGAAGAAGAGCCAGGACTTTCTCGCAACCGCAATGGA 5 TCGCAGCGCTCGCTCGCTGGCGTTGTTCTCCAGGCGCAGCCGACCGTCGTCGAGGAAGCGCCG CAACGGCTGCTCTTGGTTGAGGGCGTAGCCGAGCGCGGTGGAGACCAGGCCGCGCTCGCGGGG ACGAGCGTGCTCGGCCCTGGCCCAGGCAAAGAACGCGTCGACCAGAGGGCGGACGACGACATC GCGACGCACCTTGCGCTGCGCGGGCGGCAGGTCCGCCAGCGCGCGATCGGCGGCAAAGAGGGC GTTGATGCGCCGCAGCCCCTCGACACCGAGCTCGTGCTTGCAGACCGCCGCCTCCCAGAAGTT 0 GGTACGGCAATGCGACCAGCATCCGACTTCGGTCGGGGGCGGACCGCGCTTCTCGTCGGCAGC WO 00/22139 PCT/US99/23535 113 AGCGCCTCTTGGTGGTGTGCCGCGGAAGAGGGCGTCATAGATGGCGTGAGCGTCAGCTTGAAT ATACCGAGAGAAGCCGCGGAACATCTCGCAGACCGCGGCGCTGGTATGCTTGGGCTGGTACTC GAAGAAGACGTGATCCTTGTCCGCGAGGACGACGAAGAAGTGTCCCTTGCGGCACGGCCCGGG CTTCTTGTCCTTGCGCTCCTGGATGGGCCCAGGCTGGACGGAGACCCCGGTGGCGTCCGTGGA 5 CAGGCAGAAGGCGGTCTCGAAGGCCTCTTTGCGCGCGGCCTCGACGATGGCGCCCAGGGTCGC ACCGACGTCTTCGGCGTAGCGGCACATCGTGCCGCGATCGAGCGACGCGCCCTGAAGCTCCAG CTGCTGCTCCAGTCGATAGAACGGGACGCCGAGCAGGTACTTGCTGGTGAGGATGTGCGCAAT CATCGACGGCGCGAGGAACGACCGCCGGAACAACTCCTTCGGAAGCGGCGTCGTGATGAAGAC CGTGCAGGTCTCGCCCTTCGGCGCCGGCGGCGGCGCGTCGAGCGAGGGCGCGTCGAGCGCTGT 0 GGAGGAAGCGCTCGGCTCGCCGGCCGCTGCCGTGTCCTCCGGGCTGACGCTCGCAGCGGGCGT CGGCGTCGGGGCTTCTCTCGCGACGACCTGGAGCGGGGCCGCTTCCTCCTCGCCCGAACTGCT CGCATCCGTGACGGACCGCTCGGCCTTGTACACGACGCGTGCGAGCACGATGCGGCGCATTCC GCCGCGCTCGTAGCCGAGTCGCGAGGTCTCCTCGACCCCGATGCGCGTCGCCGTCGCATCGAG CTCGGGGCAGGAGAGCTCGATGCGGACGACGGGCAGGTCGGACTCGGACAGGTCGCGACGGCC 5 CTTGCCGCCGGACCTTCGTTTCGGCCCCTTGGGGTCGTCGTGCTGCCGCTCGTCGCCTGTATT GCGCTCGGCGGCGTCGAGTGCCTTCGCGAGGCGCTGGACCTCGAGGAACATCGAGTCGAACGC CAGCTGCTCCGCGCTCACCTCGGCGCGCTCCGCCTTGGCCACGAACAGTCGACGTCGCAGAAG CTGCAGCTGCTCGAGCGCACGGGTGTAGGCGCGCCGAAGCTGCGCGAGCGCATCGCGCGCTCC CACGAGCTCGCTCTTTGCCGCGGCGAGCTCCGCTTCGAGCTGCGCGATGCGCTGCTGCTCGGC 0 CGAGAGCGTCGGCTTGGCGGCGGCGTCGTGCACGACGCCGCTCTACGTAAGCCGCGCGTACTT GTCGAGCGAATTCGTGCGGCTCAGTGGACGCGGCGCGGTGCGCGCCTTCGCGGTTTGGACGTG GGCGCGATCTCGATGCCGTCGAGCAGCGTCTCGAGCGTGGCGTCGTCCACCTCGACGTGCGTG GCGCCCTCGGTCGGGGGGTCGGGAAGTGCGAACGCTCCGCGATCAAGGCGTTTTGAAAACAGG CAGATTCCACTGCCATCGAAGAAGAGAATCTTGATCGTGGTCCGCCGCTTGCCGACGAACGCG 5 AACAGCGCTCCGCAGCGAGCCTCGTACCCCACACGCTCACGGATGAGACCCGAAAGCCGCTCG AAGCCG WO 00/22139 PCT/US99/23535 114 (2) peptide sequence Seq ID No 48 (>pEPOcos6_ORF7.pep) MEPARSARRALLFRGKRRRDGDRPEGEVHLVVDEPGAGARPVPGGELEVAVPRPVGHRANDVG QVGLRVEPVQLAARHEREEVGRGGGVVVAAEEEPGLSNRNGSQRSLAGVVLQAQPTVVEEAP 5 QRLLLVEGVAERGGDQAALAGTSVLGPGPGKERVDQRADDDIATHLALRGRQVRQRAIGGKEG VDAPQPLDTELVLADRRLPEVGTAMRPASDFGRGRTALLVGSSASWWCAAEEGVIDGVSVSLN IPREAAEHLADRGAGMLGLVLEEDVILVREDDEEVSLAARPGLLVLALLDGPRLDGDPGGVRG QAEGGLEGLFARGLDDGAQGRTDVFGVAAHRAAIERRALKLQLLLQSIERDAEQVLAGEDVRN HRRREERPPEQLLRKRRRDEDRAGLALRRRRRRVERGRVERCGGSARLAGRCRVLRADARSGR 0 RRRGFSRDDLERGRFLLARTARIRDGPLGLVHDACEHDAAHSAALVAESRGLLDPDARRRRIE LGAGELDADDGQVGLGQVATALAAGPSFRPLGVVVLPLVACIALGGVECLREALDLEEHRVER QLLRAHLGALRLGHEQSTSQKLQLLERTGVGAPKLRERIARSHELALCRGELRFELRDALLLG RERRLGGGVVHDAALRKPRVLVERIRAAQWTRRGARLRGLDVGAISMPSSSVSSVASSTSTCV APSVGGSGSANAPRSRRFENRQIPLPSKKRILIVVRRLPTNANSAPQRASYPTRSRMRPESRS 5 KP pEPOcos6_ORF7.1 sequences: (1) nucleotide sequence D Seq ID No 49 (>pEPOcos6_ORF7.1.seq) ATGTTCCTCGAGGTCCAGCGCCTCGCGAAGGCACTCGACGCCGCCGAGCGCAATACAGGCGAC GAGCGGCAGCACGACGACCCCAAGGGGCCGAAACGAAGGTCCGGCGGCAAGGGCCGTCGCGAC CTGTCCGAGTCCGACCTGCCCGTCGTCCGCATCGAGCTCTCCTGCCCCGAGCTCGATGCGACG GCGACGCGCATCGGGGTCGAGGAGACCTCGCGACTCGGCTACGAGCGCGGCGGAATGCGCCGC 5 ATCGTGCTCGCACGCGTCGTGTACAAGGCCGAGCGGTCCGTCACGGATGCGAGCAGTTCGGGC GAGGAGGAAGCGGCCCCGCTCCAGGTCGTCGCGAGAGAAGCCCCGACGCCGACGCCCGCTGCG AGCGTCAGCCCGGAGGACACGGCAGCGGCCGGCGAGCCGAGCGCTTCCTCCACAGCGCTCGAC GCGCCCTCGCTCGACGCGCCGCCGCCGGCGCCGAAGGGCGAGACCTGCACGGTCTTCATCACG ACGCCGCTTCCGAAGGAGTTGTTCCGGCGGTCGTTCCTCGCGCCGTCGATGATTGCGCACATC 0 CTCACCAGCAAGTACCTGCTCGGCGTCCCGTTCTATCGACTGGAGCAGCAGCTGGAGCTTCAG WO 00/22139 PCT/US99/23535 115 GGCGCGTCGCTCGATCGCGGCACGATGTGCCGCTACGCCGAAGACGTCGGTGCGACCCTGGGC GCCATCGTCGAGGCCGCGCGCAAAGAGGCCTTCGAGACCGCCTTCTGCCTGTCCACGGACGCC ACCGGGGTCTCCGTCCAGCCTGGGCCCATCCAGGAGCGCAAGGACAAGAAGCCCGGGCCGTGC CGCAAGGGACACTTCTTCGTCGTCCTCGCGGACAAGGATCACGTCTTCTTCGAGTACCAGCCC 5 AAGCATACCAGCGCCGCGGTCTGCGAGATGTTCCGCGGCTTCTCTCGGTATATTCAAGCTGAC GCTCACGCCATCTATGACGCCCTCTTCCGCGGCACACCACCAAGAGGCGCTGCTGCCGACGAG AAGCGCGGTCCGCCCCCGACCGAAGTCGGATGCTGGTCGCATTGCCGTACCAACTTCTGGGAG GCGGCGGTCTGCAAGCACGAGCTCGGTGTCGAGGGGCTGCGGCGCATCAACGCCCTCTTTGCC GCCGATCGCGCGCTGGCGGACCTGCCGCCCGCGCAGCGCAAGGTGCGTCGCGATGTCGTCGTC 0 CGCCCTCTGGTCGACGCGTTCTTTGCCTGGGCCAGGGCCGAGCACGCTCGTCCCCGCGAGCGC GGCCTGGTCTCCACCGCGCTCGGCTACGCCCTCAACCAAGAGCAGCCGTTGCGGCGCTTCCTC GACGACGGTCGGCTGCGCCTGGAGAACAACGCCAGCGAGCGAGCGCTGCGATCCATTGCGGTT GCGAGAAAGTCCTGGCTCTTCTTCGGCAGCGACGACCACGCCTCCGCCGCGGCCAACCTCTTC TCGCTCGTGGCGAGCTGCAAGCTGCACGGGCTCGACCCGGAGGCCTACCTGGCCGACGTCATT 5 CGCGCGATGCCCTACTGGCCGCGGGACCGCTACCTCGAGCTCGCCCCCAGGTACTGGGCGCGC ACCCGCGCCCGGCTCGTCGACGACGAGATGAACCTCGCCCTCGGGCCGATCACCGTCCCGCCT CCGCTTCCCGCGGAAGAGCAGCGCGCGACGAGC (2) peptide sequence 0 Seq ID No 50 (>pEPOcos6ORF7.1.pep) MFLEVQRLAKALDAAERNTGDERQHDDPKGPKRRSGGKGRRDLSESDLPVVRIELSCPELDAT ATRIGVEETSRLGYERGGMRRIVLARVVYKAERSVTDASSSGEEEAAPLQVVAREAPTPTPAA SVSPEDTAAAGEPSASSTALDAPSLDAPPPAPKGETCTVFITTPLPKELFRRSFLAPSMIAHI LTSKYLLGVPFYRLEQQLELQGASJLDRGTMCRYAEDVGATLGAIVEAARKEAFETAFCLSTDA 5 TGVSVQPGPIQERKDKKPGPCRKGHFFVVLADKDHVFFEYQPKHTSAAVCEMPRGFSRYIQAD AHAIYDALFRGTPPRGAAADEKRGPPPTEVGCWSHCRTNFWEAAVCKHELGVEGLRRINALFA ADRALADLPPAQRKVRRDVVVRPLVDAFFAWAPAEHARPRERGLVSTALGYALNQEQPLRRFL DDGRLRLENNASERALRSIAVARKSWLFFGSDDHASAAANLFSLVASCKLHGLDPEAYLADVI RAMPYWPRDRYLELAPRYWARTRARLVDDEMNLALGPITVPPPLPAEEQRATS WO 00/22139 PCT/US99/23535 116 pEPOcos6_ORF7.2 sequences: (1) nucleotide sequence Seq ID No 51 (>pEPOcos6_ORF7.2.seq) 5 ATGATTCCGGCGGGCGTGCAGGTGTTCGTCGCGCTGGAGCCGGTGGACATGCGCTACGGCTTC GAGCGGCTTTCGGGTCTCATCCGTGAGCGTGTGGGGTACGAGGCTCGCTGCGGAGCGCTGTTC GCGTTCGTCGGCAAGCGGCGGACCACGATCAAGATTCTCTTCTTCGATGGCAGTGGAATCTGC CTGTTTTCAAAACGCCTTGATCGCGGAGCGTTCGCACTTCCCGACCCCCCGACCGAGGGCGCC ACGCACGTCGAGGTGGACGACGCCACGCTCGAGACGCTGCTCGACGGCATCGAGATCGCGCCC 0 ACGTCCAAACCGCGAAGGCGCGCACCGCGCCGCGTCCAC (2) peptide sequence Seq ID No 52 (>pEPOcos6_ORF7.2.pep) MIPAGVQVFVALEPVDMRYGFERLSGLIRERVGYEARCGALFAFVGKRRTTIKILFFDGSGIC 5 LFSKRLDRGAFALPDPPTEGATHVEVDDATLETLLDGIEIAPTSKPRRRAPRRVH pEPOcos6_ORF7.3 sequences: (1) nucleotide sequence 0 Seq ID No 53 (>pEPOcos6_ORF7.3.seq) ATGACAAGGACGAAGGCGACCGAAGTGATGTGGTCCGAGCGCGTTCGGGCGTGGCGCGAGAGT GGTGAAACGGCGGAGGAGTTCGCTCGGAGCCGCGGATTTGCGGCCTCGACGCTGCACGGCTGG TCGAGCCGGCTGTCGCGGGCCGAGCCACCGCGCTTTCTGCGCCTGGTGCCGAAGGCGCCCGCC GTGACGAGCAGCGCTGCGGAGCTCGTCGTCGAGGTCGGCGGCGCGCGGGTGCGCGTCGCCGCG 5 GGGTTCGACCCCGCGCTGCTGGCGGAGGTGGTCCGTGCCCTCGGCGGAGCGGGGCGA (2) peptide sequence Seq ID No 54 (>pEPOcos6_ORF7.3.pep) MTRTKATEVMWSERVRAWRESGETAEEFARSRGFAASTLHGWSSRLSRAEPPRFLRLVPKAPA D VTSSAAELVVEVGGARVRVAAGFDPALLAEVVRALGGAGR WO 00/22139 PCTIUS99/23535 117 pEPOcos6_ORF8 sequences: (1) nucleotide sequence 5 Seq ID No 55 (>pEPOcos6_ORF8.seq) ACTGGACAGCGCAGCCGGGGTGAGACGGCGCTTCGCGCAGCGCTTACGCAGAAGGCGCGCCGC GCGCCATTGTCGGATGCGGTGCGCGACTTCGCCGCCGATCGGCTGTTGCTGGAACTGGGACAA CCACTGGACGTAACGGCTGAAGCGAGCCAACGGCTCCAGCTCGCGCGGGGCGACCTGTTCGGC GCCTACCAAGCGTTGGCCCAGCTCTGGATCTGCGGCGCCCTGGCCGAACCGCCGCGACTGTAT 0 CCCGACGAACACCGCCGGCGCGTGCCGCTGCCGAGCTACCCCTTCGAGGGAAAGCGGTTCTGG ATCGAGGGCTCGCCGTTCGAAACCGCGCCCGCCGCCGGCGCCTCACCCCAACCCGCCGATTCG GGGGACATTCTCAAGGGCGACCCGGCGGACTGGTACTATCGGCCGCGTTTCGAAGCGGCGCCG CTCTTGCCCAGCCCGTTCGAGAGCGAACCCGGCGATTGGCTGGTGTTCGAAGATGAGCTGGGG CTCGGCGCCTGGCTGAGCGAGACCTTGCGCGACAAGGGCGCGCGGGTCGCGACAGTCGTTCGA 5 GGCACCGAGTTCCGACGCCTGGCGTCACAGCGCTTCCAGCTTCGTCCCGATCGACGGGACGAT TACCGGACCCTGCTGCACGAGTTGAAGGCGCAGGGCATCGCGCCGGTCCACCTGTGCCACCTA TGGAGCGTGACCGCCGCACCGGATGCCGAGCAGTTGCTCGACGTCAGCTTTCACAGCCTGGTC CATTTGGCGGCCGCTTTGGGTTCGGTTGGCTACTTCCACGCCATG 0 (2) peptide sequence Seq ID No 56 (>pEPOcos6_ORF8.pep) TGQRSRGETALRAALTQKARRAPLSDAVRDFAADRLLLELGQPLDVTAEASQRLQLARGDLFG AYQALAQLWICGALAEPPRLYPDEHRRRVPLPSYPFEGKRFWIEGSPFETAPAAGASPQPADS GDILKGDPADWYYRPRFEAAPLLPSPFESEPGDWLVFEDELGLGAWLSETLRDKGARVATVVR 5 GTEFRRLASQRFQLRPDRRDDYRTLLHELKAQGIAPVHLCHLWSVTAAPDAEQLLDVSFHSLV HLAAALGSVGYFHAM WO 00/22139 PCTIUS99/23535 118 pEPOcos6_ORF9 sequences: (1) nucleotide sequence Seq ID No 57 (>pEPOcos6_ORF9.seq) D ATGAAGTTGAACGTGGTCGCCAACCGGCTATTCGACCCCGAGTCGCCCGAGCGCACCGAGCCC GCCAAGAGTCTGTTGCTCGCGGTGACCAAAGTCCTGCCGCAAGAGGTGCCCAACGTTCGAACC CGCGCCATCAGCGTGGACCTGGATCGCTCGTTCGACGCGGCGGCGCCCGCCTGGGCCGCCAGT TTGTTGGTTGAATGCGGCGCGCCCGTCGAGGAAACGGTGGTGACCTACCATGGCGCAGCCCGA TGGCTGCGCCGCTTCGATCGCGTTGCGGTGAATGGTCTCGGCCCGTTCCACCCCGATCAACCT D GCGCCGCTGCTGCGCGAGCGCGGCGTGTACCTGATCACCGGCGGCCTGGGCGGCGTGGCTGGC CAGTTGGCGCGCTACCTGGCGCGGGCCTGCCGGGCGCGGTTGGTGCTCACCGCGCGCCGGCCC CTGCCCGAGCGCGACCAGTGGGATCGGGAGTCGGCCGTGCTGTCATGGGACGACAAGACGCGC CAGCGCATCGAGCTGGTGCGCGAGCTGGAGCGGCTGGGGGCCGAAGTATTGGTGGTGGCTGCC GATGTCGCCGACGAAGCGGCCATGGCGCAGGCGATCGAGGCCTCACTGGCGCGATTCGACGCT D TTGGACGGCTTGATCCACGGCGCCGGGATCGTGCGGGTCGCGTCGGGCCGCACGCCGATCGGG AGTATGACGCGGGCCATGTGCGAGGAGCAGCTCCGCCCCAAGATGTTGGGCCTCGACGTCGTC GACCGCCTCCTGCGCGATCGCCGGTTGGACTTCCGCATTGCCATCTCGTCGCTCGCCCCGATT CTCGGCGGCCTCGGCCACGTCGCCTACGCCGCCGCCAACCTCTACATGGACGCGTTCGCGACG CGCGCCGCCGCCGGCAACGCGCCTTGGATCGCGCTGAACCTGGCCGAGTGGGAATACGAGGGC D CCGGCTACCTACGACGAGCGGGTGGGCCGTTCGCTCAAGCAGCTCGAGCTCACCAACGAGGAG GGTATCCGCGTCTTCCAGACGGTGTTGGCCTTGGCCGCGCGCGGCCCGCTACAGCAGATCATT ATTTCCACCGGCGACCTCCAGGCCCGCCTCGACAAATGGATTCACATCAAATCCCTGCATCGC CGACCGGGGCCGGTCCAGCTCAGTCGCCGGACCGCGGCACCCCAGGGCGGTTTCGGCTCGGAG CGCGCCGCCTTCGAGGCCGCCTTCGCTGACGCCTGGTGCGACTTCTTCGGGGTTGAAGAGGTC 5 GACCCGAACAAAAACTTCTTCGATCTGGGCGCCAGCTCGCTCGACTTCATCCACCTCGTCAGT CGCTTCAGCAAGGCCATCGAACAGCATGTACCGCTCGAGGCCCTGCTCGAACACTCCACCCTG CACGACCTCGCCGCCCACCTCGCGGGCGACGCGAACACCGACGCCAGCGACGAAGCGCGCATT CGCCAACGGCTGCAAGGCGCCAAGTCCGGCGACATCGCCATCATCGGCATGGCCGGCCGCTTC CCGCTCGCGCCCGACCTGGACACCTATTGGCGCAACCTGGTCGGAGGCATCGACGCGGTCAGC D TTCTTCAGCGCCGAGGAGTTGCGTGCTGCTGGCGTCACCGCGGCCGAGATCCACCACACCAAC WO 00/22139 PCT/US99/23535 119 TACGTGCCGGCCAAGGGGCGCTGC-GC CGACCAGGACTTGTTCGATGCGGCCTTCTTCGAATAC ACTGCCAGCGACGCCGAGCTGATGG -ACCCGCAAAATCGCGTGTTACACGAG-GTCGTGTGGCAC GCGCTGGAAGACGCCTGTTTCGAC7TCAIACGGCGATCACGGCCAGGTCGGCCTGTTCGCGGGC GCCTCGCCGAACCTGTGGTGGCA-TTCGTGGCCAGCTTTTCCGAGGCCGCCAAGACGCAGGGC 5 ATGTTCACCACCACCCTGCTCAIACGACAAGGACTCGATCGCGACCCAGATTTCATACAAGCTC GGTCTAAAGGGCCCCGCGGTCACC -TTGTTCACCGGCTGTTCCACCTCGCTGGTAGCCGTTGAC GCCGCCTGCCGCTCGATCTGGTCCGG''TCAATCGGACATGGCCGTGGCCGGCGCGGTCTCGCTG ACTCTCCCCGATAAGGCCGGCTACATCTACGAAAAGGGCATGCTCTTCTCGGCCGACGGCCAT TGCCGGGCTTTCGACGCCAACGCCACCGOCATGGTCTTCGGCGACGGCGCCGGCGCGATCGTG 0 CTCAAGCCGTTGGACGCGGCCCTGCG -CGACGGCGACCCGATCCATGCGGTGATCAAGGGCTGC GCCACCAACAACGACGGCGACC-CAAAGCCGGCTACACGAGCGTCAGCGCCCAAGGCC-AGGCC GAGGTGATCCGCTCGGCCCAGATC CTGGCCGACGTGGCGCCCGAATCCATCAGCTACGTGGAA GCCCACGGTACCGGCACCAAGTTG'GCGACTCGATCGAGATCAGGCGTTGAAIGCkJAGCCTTC GCCAGCGACAAGACGGATTTTGCG-GCATCGGGTCGCTCAAGACCACCTCGGTCACCTGATG 5GCGGCGGCGGGGATGGCCGGCCTGATCAGACGGZTTCTGGCGATGAGCACCGCCAATTGCCG CCATCGCTGCACTGCGACGAAGTGAACCCCGACCTGGAGTTGGAGCGCAGTCCGTTCTACATC AACACCCGCCTGCGCGACTGGGTTG -CACCGGGCGGGCCGCTGCGGGCCGGCGTGAGTTCGTTC GGGATCGGCGGAACCAACGCTCACGTCATCCTGGAGGAGCCGCCGACGCGCGAGAGCGGCACG CGCATGCGCCACTGGAAATTATTG-ATGCTGTCGGCGGCCAGCGAGGCGGCGCTCGACCGCCAG 0 GCCGATAACCTGGCCGACTACCTG;GAGCGCCATCCCGAGGCCCACCTCAGCGACGTGGCCTAT TCCCTCCAGACCGGCCGGCGCGTT CTGGCCTGGCGGCGCACGGTCCTATGCGAGTACCGCGAC GACGCGGTGACCAGTCTGCGCGAGCGACAGGCCAGCGCGTCCAGACAAGTCGCGTCCGCTGG GACCACAAGGACGTGGTCTTCATG TTTCCCGGTCAGGGCGCCCAGTACCTCAACATGGGCCGC GACTTATACGTCATGGAGCCGGTCT'-TCCGCGAGGTCATGGACCGCTGCTTCGAGTTGCTGGCC 5CCTTTGTGGTCCGAGCATCCGCGC CAGATCCTTTATCCGGAGGGCGGGGTGTCGACCCTCCTC CACCGGACTGATTACACCCACCGk:ATCGTGTTCTGCTTCGAGTACGCCCTCGCCCATTTGCTG CTCTCCTGGGGATTGAAGCCGGCCG- -CGACCATCGGCTACAGCTTCGGCGAGTACGTTTCTGCC TGCCTCGCCGGCGTCTTCTCCCTGG,--AAGATGCGATCCGTCTGGTGACCGAGCGCGGTCGGCTG ATGGCGGCTTTGCCCGCGGGCGCC-ATGCTCAGCGTCCCGGTTCCCGAATGCGAGCTGCTGCGG 0 CTGCTGGACGGCTTCCACGCCCAA7TCGGCGGCCCATCTGGCGCTGGCCGTCGACAATGGCGCC WO 00/22139 PCT/US99/23535 120 TCCTGCATTGTGGCCGGCGAGCAGGCCGCCATCTCGGCCTTCGAATCGATGCTTCGCAAGAAG CGTCTGTTGACCATGCGGGTCGCGGTCAGCCACGCCGCTCATTCGCAGGTCATGACCGGCGCG ACCGACGCCCTGCGCAGCATCCTGCGGAAGATCCCCCTCTCCGCGCCGACAATTCCCTTCATT TCCTGCGTCACCGGCACCTGGATCACTGCACAGCAGGCTACGGATCGCGAGTATTGGGTGAAC 5 CACATGTGCGGGACGGTGCGGTTCGCGGCGGGTCTGACCGAGCTGGGTCAAAACCGCGAGGCG GTGTTCCTGGAAGTAGGTCCGGGCCGCGACTTGACGTTGCTGGCCCACCGCATCCTGGCCGAC AGCGCGGCCGTGTTCGAGCTGGTCAAGGCGCCCGACGGCGGCGACGACGATGGGTTCCTCCTG CTGGATCGATTGGCCAAGCTCTGGAGGCTGGGGATTTCGATTGACTGGGCCGGCTTCTACGCG GATGAGCGGCGGCGGAAACTCTCGCTGCCGGGATATCCGTTCGAGCGGCGGCGCTTCTGGATC 0 GAGGGCAACCCGCTGGAGATCGCCGCCGGCAGGCCCAATGTCCAGGGGCCGCTGGTCAAGGCG TCGGACATCGGCGCTTGGTTCTACGTGCCGCAATGGCGGCGGTCGGTGCTCGCCGAGCCGGGT ACAACGGCGGCGGGCGCCGCCGTCACGGCGGAGCAGGCACGCGTCGTGACCGAGCTACGGGCG GGATGCGCGTCGGCCGGCTTGGGCAGCGGGGCCTGCGGACTGAATGGCGGTGCCCCGTCCGAG CGTCCGAAAGAAAGTGTAGCGCCAGCCGGGTCGACCAGCGCAGCGGCGCAGACCGGCGCGGAC 5 TGCCCGACACCGACTGGGGAGCCAGCGGCTGTGCCAAAGGACGGGGCCGAGCCGCGGCCGACC TGGCTTATTTTCGCCGACGCCGGCGGATTGGCCGAATCTTTCGCCAAGCGGGTTCAGGCCCGC GGCGAGAAGCTTTACCTGGTGGCTTCCGGCTCGCGCTTCGAGCGCCTGGCCGAGACCCGCTTC CGCCTCGATCCCGGGGCCAAGTCCGATCACCGCCTGCTTTTCAAGGCGCTCGACGAGGCCGAC ATCCTGCCGACCCACCTCCTCGACTTCCGCTCGCTTGACTGCGGCGGGCCCGACGCCGACCCC 0 ATGGACCAGGCCGGCTTCTTCGGGCTGTTGCACCTGGTCCAGGCGATGGCAGAGGCCGGCTAC AGCCATCCCATTCGGCTGCTGATCGTCAGTTGCGGCGTCTACGATGTCACCGGTGCCGAACCG CTGCAGCCGGCGCGGGCCACGATGATCGGACCGGCTCTGTGCATCCCGCAACAGTATCCGCAC CTCGAAACGAGCCATGTGGATTTGGGCGTGGTCCATGCCGACGAGCTCCACGCCGCGCGCCAG CTCGACAGCCTACTTGCCGAATGCCTAAGTGCAACGGCCGAGCGCCAATTGGCGCTGCGCGGC 5 CGACACCGCTGGCTGCTGGACTACGAGCCAGTCCGCTTGCCGCCGCTCGACCCGGGCCGTCTG CCCTGGCGCCAGCGCGGGGTCTACTTGATCACCGGCGGTTTGGGCGGGATCGGCCGCATCCTG GCCGAACACCTGGCCCGCACGACCTCGGCTCGCCTGGTCCTAATCGGCCGCGAAACCCTGCCC GACCGCGACGACTGGGACGCCTGCTGAACCGCCCGCAACCGGTCGACGCCACCCACGAACGG CTGCTGCACAAGATCCGCGCGATTCGCGATCTGGAAGCGCTAGGCGCCGAAGTCCTGGTCCTC 0 GCC3CCGACGTCGCCAACGAAGCCGCCATGCGCGAGGCCTACGATCGCGCCGAATCCCACTTC WO 00/22139 PCT/US99/23535 121 GGCACAATCCACGGGGTGATTCACGGCGCCGGCCTGATGGACGCGCAAAGCTTCTCACTGATC GACGCCCTCGACCACGACCTCTGCGCCCGCCAGTTCGAAGCAAAAATCCGCGGCGTCTGCGTG CTCGACCGCGTTCTGGCCGACCGCACGCTCGACTTCTGTCTGCTGATGTCTTCCATCTCCACC GTGCTCGGCGGCCTGGGCTATTTCGGTTACGCCGCGGCCAACGCCTTCCTCGACGCCTTCGCC D CAGGCGCGCAGCCGCGACGCCGCTTTCCCCTGGCTTAGCGTGGCCTGGAGCGATTGGAAGTAC TGGACCGAGCGCAAGATGGACAACGAGGTCGGCGCCGTCATCGACAGCCTCTCGATGGAACCC GCCGAGGGCTTCGAAGCCGTCACCCGCGTCTTGGCTTGGGGCAAGGCGCCCCACATCGCCAAC TCGCCCGGTGACCTCGGTCGCCGCCGGGATCAATGGGTCAAACTGGCCAGCCTGAAATCGGCG CACTCCAGCGAGCCCGAGCCGGCTAGGCATGGACGTCCGGCGCTCTCCAGCGAATGGGTCGCG J CCGCGCAACGTGGTCGAAGAGAAGCTGGTCGCCATTTTCGAGCAGGTGTTCGGCACTGCGGCA CTGGGCATCGAGGACAACTTCTTTGAGTTGCGCGGCGACTCGCTCAAGGCGGTCATGACCGCG GCCCGTATTCAAAAGGAGCTGAACGTGGAAGTGCCGCTGCCGACCTTCTTCCAGATGCCCACG GTCGCTGGCCTGGCCCAGTTCGTGACGCAAGCCAAGCGCAGCGGCCGGGAGACGATTCGGCGC ACCGCGCCGCGCCCACATTACCCGCTCTCGGCTGCCCAGGGCCGCCATTACCTGCACTACCGC 5 ATGGACCCGCGTTGTACCGCATACAACGATCCCTTCGCCAACCTGATCGAGGGTCCGCTGGAC GTGGATCGCGTGGAGCGCATCCTGCACACCCTCATCCTACGCCACGACTGCTTCCGCACCTCG TTCCACTTCCGCGAGGGCGAGCCGGTCCAGGTGATTCACGATCGGGTGGACTTCAACCTGGCG CGGATTACCTGCGCGCCCGAGGATTTGCCCGAACGGATGCGCGATTTCATCCGCTCCTTCGAT CTGGAGCGACCGCCCGCCATGCGCGCCGGCCTCTTCGTCACGGGGCCCGAGCGCCACGTGCTG D CTAATCGATTTTCACCACATTATCACCGATGGCGTGTCGTTCGAGAACTTCGTCGGCGAGTTC GCGGCGCTCTACCGCGGCGAGATCCTGCCCGAGCTGGAACTCGAGTACAAGGATTTCGCGGTG TGGCAGCATGAGAACCGGGGCCGCCGCGCCAACAGCGACCAGGCCCGCTACTGGACCGAGCAG TTGGCCAATGCGCCCGGGCCGATCGAGCTAACCACCGATTTCCCCCGTCCCAGTCGACGCAGC TTCCGCGGCGACCGCGTGCGGACCGTGCTTGATGCGGAGCTCGTTGCTCGACTCAAAGAGCAC 5 GCGGCGCGCCTCGGCATCACCCTCTATAGCCTGCTGCTGGGCGGATTCTCGTTATTGCAGCAC AAGCTCTCCGACTCGCACGACATCGTCATCGGTTCGCCCGTCGCGGGCCGCACCCGGAGCGAA CTCCAGGATCTGCTGGGCGCGTTCGTCAACACCCTGCCGATGCGCCACCGCATCGACCCGACC CATACCGCACGGGTCTTCTTGGAGCAGGTCCACCAGACAACCTTGGCGGCCCTCAGCTACCAG GAGCACCCTTTTGACGAAATGGTGGCGACGCTCGGGTTCGCCGCCGATCCGGCTCGCAACCCG D ATCTTCGACACGATGTTCTTGCTGCAGAACATGGCCATGGGTGCAACCACCATTCCCGGTCTG WO 00/22139 PCT/US99/23535 122 CGGCTCTCGCCTCACGACACTTTTCACCGCAAGGCATTGTGCGACCTGATGCTACAGGCGACC GAGTATGACTGCCACCTGGAGCTGGTGCTCGAGTTCGCCACCGACCTGTTCCGGCTGGAAACC GCGCAAGTCTTGCTCGACCGCTACCGCCAAGTCTTGGAGTGGCTGTTGGCGTACCCCCATGAA TCGATAGACGATTTGACGCTCGCCGGCCACTTTCGCGAAGTCGAAGTGACGATGTCGGACGAG 5 GGCGACTTTGATTTCTCAGATTTCGAACCCCGCAACGTGAGAAACCTATGGCGCGCC (2) peptide sequence Seq ID No 58 (>pEPOcos6_ORF9.pep) MKLNVVANRLFDPESPERTEPAKSLLLAVTKVLPQEVPNVRTRAISVDLDRSFDAAAPAWAAS 0 LLVECGAPVEETVVTYHGAARWLRRFDRVAVNGLGPFHPDQPAPLLRERGVYLITGGLGGVAG QLARYLARACRARLVLTARRPLPERDQWDRESAVLSWDDKTRQRIELVRELERLGAEVLVVAA DVADEAAMAQAIEASLARFDALDGLIHGAGIVRVASGRTPIGSMTAMCEEQLRPKMLGLDVV DRLLRDRRLDFRIAISSLAPILGGLGHVAYAAANLYMDAFATRAAAGNAPWIALNLAEWEYEG PATYDERVGRSLKQLELTNEEGIRVFQTVLALAARGPLQQIIISTGDLQARLDKWIHIKSLHR 5 RPGPVQLSRRTAAPQGGFGSERAAFEAAFADAWCDFFGVEEVDPNKNFFDLGASSLDFIHLVS RFSKAIEQHVPLEALLEHSTLHDLAAHLAGDANTDASDEARIRQRLQGAKSGDIAIIGMAGRF PLAPDLDTYWRNLVGGIDAVSFFSAEELRAAGVTAAEIHHTNYVPAKGRCADQDLFDAAFFEY TASDAELMDPQNRVLHEVVWHALEDACFDFNGDHGQVGLFAGASPNLWWQFVASFSEAAKTQG MFTTTLLNDKDSIATQISYKLGLKGPAVTLFTGCSTSLVAVDAACRSIWSGQSDMAVAGAVSL 0 TLPDKAGYIYEKGMLFSADGHCRAFDANATGMVFGDGAGAIVLKPLDAALRDGDPIHAVIKGC ATNNDGDRKAGYTSVSAQGQAEVIRSAQILADVAPESISYVEAHGTGTKLGDSIEIKALKQAF ASDKNGFCGIGSVKTNLGHLMAAAGMAGLIKTVLAMKHRQLPPSLHCDEVNPDLELERSPFYI NTRLRDWVAPGGPLRAGVSSFGIGGTNAHVILEEPPTRESGTRMRHWKLLMLSAASEAALDRQ ADNLADYLERHPEAHLSDVAYSLQTGRRVLAWRRTVLCEYREDAVTSLRERQAKRVQTSRVRW 5 DHKDVVFMFPGQGAQYLNMGRDLYVMEPVFREVMDRCFELLAPLWSEHPRQILYPEGGVSTLL HRTDYTQPIVFCFEYALAHLLLSWGLKPAATIGYSFGEYVSACLAGVFSLEDAIRLVTERGRL MAALPAGAMLSVPVPECELLRLLDGFHAQSAAHLALAVDNGASCIVAGEQAAISAFESMLRKK RLLTMRVAVSHAAHSQVMTGATDALRSILRKIPLSAPTIPFISCVTGTWITAQQATDREYWVN HMCGTVRFAAGLTELGQNREAVFLEVGPGRDLTLLAHRILADSAAVFELVKAPDGGDDDGFLL 0 LDRLAKLWRLGISIDWAGFYADERRRKLSLPGYPFERRRFWIEGNPLEIAAGRPNVQGPLVKA WO 00/22139 PCT/US99/23535 123 SDIGAWFYVPQWRRSVLAEPGTTAAGAAVTAEQARVVTELRAGCASAGLGSGACGLNGGAPSE RPKESVAPAGSTSAAAQTGADCPTPTGEPAAVPKDGAEPRPTWLIFADAGGLAESFAKRVQAR GEKLYLVASGSRFERLAETRFRLDPGAKSDHRLLFKALDEADILPTHLLDFRSLDCGGPDADP MDQAGFFGLLHLVQAMAEAGYSHPIRLLIVSCGVYDVTGAEPLQPARATMIGPALCIPQQYPH 5 LETSHVDLGVVHADELHAARQLDSLLAECLSATAERQLALRGRHRWLLDYEPVRLPPLDPGRL PWRQRGVYLITGGLGGIGRILAEHLARTTSARLVLIGRETLPDRDDWDAWLNRPQPVDATHER LLHKIRAIRDLEALGAEVLVLAADVANEAAMREAYDPAESHFGTIHGVIHGAGLMDAQSFSLI DALDHDLCARQFEAKIRGVCVLDRVLADRTLDFCLLMSSISTVLGGLGYFGYAAANAFLDAFA QARSRDAAFPWLSVAWSDWKYWTERKMDNEVGAVIDSLSMEPAEGFEAVTRVLAWGKAPHIAN 0 SPGDLGRRRDQWVKLASLKSAHSSEPEPARHGRPALSSEWVAPRNVVEEKLVAIFEQVFGTAA LGIEDNFFELRGDSLKAVMTAARI QKELNVEVPLPTFFQMPTVAGLAQFVTQAKRSGRETIRR TAPRPHYPLSAAQGRHYLHYRMDPRCTAYNDPFANLIEGPLDVDRVERILHTLILRHDCFRTS FHFREGEPVQVIHDRVDFNLARITCAPEDLPERMRDFIRSFDLERPPAMRAGLFVTGPERHVL LIDFHHIITDGVSFENFVGEFAALYRGEILPELELEYKDFAVWQHENRGRRANSDQARYWTEQ 5 LANAPGPIELTTDFPRPSRRSFRGDRVRTVLDAELVARLKEHAARLGITLYSLLLGGFSLLQH KLSDSHDIVIGSPVAGRTRSELQDLLGAFVNTLPMRHRIDPTHTARVFLEQVHQTTLAALSYQ EHPFDEMVATLGFAADPARNPIFDTMFLLQNMAMGATTIPGLRLSPHDTFHRKALCDLMLQAT EYDCHLELVLEFATDLFRLETAQVLLDRYRQVLEWLLAYPHESIDDLTLAGHFREVEVTMSDE GDFDFSDFEPRNVRNLWRA 0 pEPOcos6_ORF1O sequences: (1) nucleotide sequence Seq ID No 59 (>pEPOcos6_ORF1O.seq) 5 ATGGCGCGCCTGAGCCGCACAGATCTCCAACTCGCCATTCACCAGCGCACCGTGGAGCGCGAA TATTGGCGCGCTCTGTTCGAGCGCCATCCGCAACGGTCCAGTTTGCCGGGGGTGCTCACCGCC CCGATCGGCGACGAGTCGACCCGCGAGACCTTGTCATTCGTCCTCGACGAAGATCCCCTTCGG CTGAGTAATCGTTCGCCGCAACG-CCTGCTCACGGTGTTGGCGGCTGGCCTCGCGGCTTTCCTC CACCGCTGCGACGGCGCTGAGCGCTTCACCCTGGGGTTGGCCCTACCGCGCCAAGCCGATGAC 0 CATCACCCGATCCTCAACAGCTTGATCGCGCTGGGGGTCGCGGTCGACTCGAGTACGACCTTC WO 00/22139 PCT/US99/23535 124 CGCGATCTGCTCTATGCGCTTCGATCCGAATACCACGAGGCGATGCGCCACGCCAACTTTCCG CTGGCGACCTGGTGGCGCGGCCTACCCGGCGGAACGGCGCCGTTCGACGTCGCCCTCAGCCTG GACCCCTTCACAGACGGCGATTCGCTGGAAGACCACGCGATCGGCGCGTTGTTCCGGTTCGCA TTGGAGGGTGAGCGCCTCACCTGCCGATTGCGATTCGACCCTGCGCGCTATGACCGTCCCGCG 5 ATCGAAAACCTCGCCGATCGTTTCGCCCGCTTCCTCACGCGCCTGTGCCGGGACGCCTCCACC GTCATCCAGGCGCTGGACCTTTCGCTGCCAAGCGATGAATCGGTGTGGCGCGTCACTGAAGGC GTGCGGCGCGGCTATTCGCAAGACCTGACGCTAGACCGCGCGTTCCGCCGCCAGGCCGCGCAA ACGCCCGATCAGCCGGCGATCACGTTGAACGGGGACGTCCAGAGCTACGCCGAGGTCGACCGC CGCAGCGACGCGCTGGCCCGCCACCTCCGTCGCCACGGCGTCGGTCCGGAAACGATTGTGGCC 0 GTCAACGCCCGGCGCGGGCCTAATCACCTGACGGCCCTGCTCGCGGTCCATAAGGCCGGCGGC GCCTACCTGCCGATCGATGCCGAGGAGCCGGCTGCCCGCCAGCAATTCAAGGTGCGCGACAGC GGGGCGCGGTTGGCACTGGAGCCGTCGCCGGACCAGGCGCTGACCGTCACCGACCTGCCGCGG CTCTTCCTGGACGATGCCTCGCTCTTCGCTGACGGCGGGCTCGATGTGCCGCGCGGCGCCGAC TCGCTCAATCCGGCCTATGTGATGTACACGTCCGGCTCGACCGGACAGCCCAAGGGTGTGGTG 5 GTTCCCCACCGCGGCGTGGTCAATCGTTTGAATTGGGGGCAGTCCCGTTTCCCGCTGGACGAA CGCGACCGAATCCTCCAAAAGACGCCGCTGCTGTTCGACGTGTCGGTCTACGAGCTGTTCTGG GGCGCATGGAGCGGGGCCACCCTGGACATCCTCGAGCCCGGCGCCGAGCGCGACCCCGACGCA GTGGCCAGGGCCCTGGCCGAGCGCGCCATTACCGTATGCCATTTCGTGCCTTCGATGCTGCTC GTCTACTTGGAAGTCATGCGGCGGCACCATGCGCCGCCCGTGCCGGACCGGCTCCGTTACGTC 0 TTCGTCAGTGGCGAGGCCCTCGAACCGGACCACCTCGCCGGGCTCCAGCAGATTGGTCGGCGC CTCGGCCGCACGATTCCCCTCGTTAATCTGTATGGACCAACCGAGGCCTCGATCGAAGTCTCC TGCTTCGCCTGTCCCGCCGACCATGTGCCGCGCCGGATCCCCATCGGGCAGCCGATCGACAAC GTCGCACTGCACGTTCTCGACCGGCGCGGCCGTCGCCAGCCGCCCTATCTTCCTGGCGAGCTG TTCCTGGCCGGCGACTGCCTGGCGCGCGGCTACCTCAACCGTCCCGACCTGACCGCGCTCCAC 5 TTCGTGCCCAATCCCTTCGGCAACGGCGAGCGCATGTACCACAGCGGCGACTTGGCGCTCGTG CGCGGCGACGGCCAAGTGGCGTTTCTCGGCCGCCGTGACCACCAAATCAAAATCCGTGGTCAA CGGGTCGAACTGGGCGAAATCGAGAGTCATTTGCGCGGGCTCGAAGGCATCGCCGCCGCCGTC GTCCAGGCCGAGTCGCAGCACCATGAAACCCTGCTGCACGCCTACGTCGTCACCAACGACGCG GGCCTCAATGCGGCCCGGCTGCGCGCCGCCCTCGCTCAACATCTGCCCGAGTACATGATTCCC 0 CAGCGCTTCTCGCGGCTGGCCGAGTTGCCGCTGCTGGCGGCAGGCAAGATCGACCGCGCCGCC WO 00/22139 PCT/US99/23535 125 CTCGCGCAACGTGCAACGCCGCTCGCCAGCGGCGCGCCCTTCGTGGAACCCAGCGGGCCCACC CAGCAGCGTATCGCAGAACTGTGGCGCCAGGTCTTAGCGGTCGCCGAAGTCGGCGCCGAGGAT CCCTTCTTCAGCATCGGCGGCAACTCGCTCAATGTGCTCAAGCTCAGCGCCGCGCTGAGCGAC GCCTTCGCGCGTGACATTCCCATGCCGGCCCTGTTCCAATACGACACCATCGCCGCCCAGGCC 5 TCCTGGCTCGACGGGCAGGTTGACGAACGGGCCCAATCCGCCGCGCTCGACCGGCAGGCCGCC GAGGCGGCGCTGACCCTTCAAGAGACCGTGGCCATTTTTGAGGGATTCGATGACGAACCA (2) peptide sequence Seq ID No 60 (>pEPOcos6_ORF1O.pep) 0 MARLSRTDLQLAIHQRTVEREYWRALFERHPQRSSLPGVLTAPIGDESTRETLSFVLDEDPLR LSNRSPQRLLTVLAAGLAAFLHRCDGAERFTLGLALPRQADDHHPILNSLIALGVAVDSSTTF RDLLYALRSEYHEAMRHANFPLATWWRGLPGGTAPFDVALSLDPFTDGDSLEDHATGALFRFA LEGERLTCRLRFDPARYDRPAIENLADRFARFLTRLCRDASTVIQALDLSLPSDESVWRVTEG VRRGYSQDLTLDRAFRRQAAQTPDQPAITLNGDVQSYAEVDRRSDALARHLRRHGVGPETIVA 5 VNARRGPNQLTALLAVHKAGGAYLPIDAEEPAARQQFKVRDSGARLALEPSPDQALTVTDLPR LFLDDASLFADGGLDVPRGADSLNPAYVMYTSGSTGQPKGVVVPHRGVVNRLNWGQSRFPLDE RDRILQKTPLLFDVSVYELFWGAWSGATLDILEPGAERDPDAVAPALAERAITVCHFVPSMLL VYLEVMRRHHAPPVPDRLRYVFVSGEALEPDHLAGLQQIGRRLGRTIPLVNLYGPTEASIEVS CFACPADHVPRRIPIGQPIDNVALHVLDRRGRRQPPYLPGELFLAGDCLARGYLNRPDLTALH 0 FVPNPFGNGERMYHSGDLALVRGDGQVAFLGRRDHQIKIRGQRVELGEIESHLRGLEGIAAAV VQAESQHHETLLHAYVVTNDAGLNAARLRAALAQHLPEYMIPQRFSRLAELPLLAAGKIDPAA LAQRATPLASGAPFVEPSGPTQQRIAELWRQVLAVAEVGAEDPFFSIGGNSLNVLKLSAALSD AFARDIPMPALFQYDTIAAQASWLDGQVDERAQSAALDRQAAEAALTLQETVAIFEGFDDEP 5 WO 00/22139 PCT/US99/23535 126 pEPOcos6_ORF11 sequences: (1) nucleotide sequence Seq ID No 61 (>pEPOcos6_ORF11.seq) 5 ATGACGAACCATGACCATCACGAGGAGAGCAGCGGCCTGGAGATCGCCGTCATCAGCATGGCC TGCCGATTCCCGGGTGCTATGGCCTGCCGATTCCCGGGTGCTGCCGATTGCGACGCATTCTGG GAAAACCTGATCAACGGGACCTCCTCGATCACCCATTTCAGCGACGACGAGCTGATCGCGGCC GGCGTTGACGCGCGCGACCTGACGCCGCAGTACGTGCGCGCGGCCGGCCAGATCGATGACGCC GAACGGTTCGACGCGGCCTTCTTTGGGTACTCCCAGCGTGAGGCCGAGCTGATGGACCCCCAG 0 TTCCGCCTGCTCCATGAATGCGCCrTGGTCCTGTCTGGAACAGGCCGGCATCGATCCGCGCGTC GAAGCCGCGCCGATCGGGCTGTATGCCGGCGCAGCCGACAACACCTACTGGAACGCGCTCTCG TCGCTCGACCGGGGCTCGGCCGAATCGGAGCAATTCGCCGCCGAACAACTTTGCAACCGCGAT TTTCTGTGCACGCTGGTCGCCGCCGCGCTCAACCTGAAAGGCCCCGCGGTGGTGGTTCAAAGC GCCTGTTCGACCTCGCTGTTGGCGGTCCACTCGGCCTGTCGTGCGCTCCTGACCGGCGAATGC 5 CGAGTGGCCTTGGCCGGTGGGGTGGCGCTGCGCTTCCCACGCCCGAGCGGTTATCGCTACGAA CCTGGCATGATCTTCTCGCCCGACGGGGTGTGCCGGCCGTTCGACGCGGGCGCTAACGGGACG GTGCCCGGCGAAGGCGCGGGGCTGGTAGCGTTGAAGACGCTGAAACGTGCCCTCCAGGACGGC GACACGATCCACGCCGTGATTCGCGCGACCGCGGCAAACAACGATGGTGCCCGCAAGACCGGG TTCACCGCGCCCAGCGCCCACGGCCAAGCCGAAGTCATTCGCACGGCGCTGCGCCTGGCCCGG 0 GTGCCGGCCGAATCGATCGACTACGTCGAGGCCCACGGAACCGGCACGCCGCTAGGCGACCCG ATCGAGGTAGCCGGCTTGGTGGAGGCCTTCGCCAGCGAGAAGCGCGGCTATTGCCGGCTGGGC TCGGTCAAATCCAACCTTGGTCATCTGGACACTGCTGCCGGCATCGCCGGCCTGATCAAGACC GTGCTGGCGCTCGAGCACGCGCACATCCCCAAGTCCTGCCACGTCGCCACGCCCAACCCCGCG GCGCGCCTACACAAGACGCCTTTCCGCATTGCCGCCGACGGGATGGCCTGGCCGCGGCGTATG 5 GCGACGCCGCGGCGGGCGGCGGTGAGTTCGTTCGGCATCGGCGGCACCAACGTCCACGCGATT TTGGAGGAGGCGCCGCCCCGCGCGCCCGAGCTGGCGGACGGGCGCAGTCAGGTGTTCGTCTTC TCCGCCAAGGACGAGGCGGCGCTGGACCGTGCCCTTGCCAACTATGGTGCGGCCTTGGAGAAG CGCGGCGACCTCGCGGCGGGCGCGGTGGCCTGGACGCTCCAAAACGGCCGGGCCGCATTCGAA TGGCGAGCCAGCGCGGTGGCATC CGACCTCGACGAATTGGCGGGCGCATTGCGCGGCGAGCGG 0 CCCGGCGCCGTCAAGAAAAACCGAATGGCGCGCGAGGATAAGCCGGTGGCGTTCTTATGTTCG WO 00/22139 PCT/US99/23535 127 GGGCAGGGGAGCCAGTACCGTGGCATGGGCCACGACCTGTACCGCGAJAGAGCCGCGTTTCCGG CACCACCTCGACGCCTGCCTCGCCATCCTCGCCGACACAAGCCCGAGATCGACTGGCTGGCG TTGCTGGGCTACCGCGACGAGGACGAGCCAACCGACCAGATCGGGACGTCCTCGCAGGGCCCG AGCCGGTCAGCCGCATCGAACCCAGCGGAGCTCCTCGACAGCACCGATTCGCCCAJCCTTTG 5 CTTTTCTCCATGTCCTACGCGCTCGGTCGGCTGTGGCTCGACTGGGGCGTGCGACCCACGGCG ATGATCGGGCACAGCCTGGGCGAGTACAGTGCTGCATGTATTGCAGATTTCTATGCACTCGAT CAGGTGCTGCCCTTCATTCTGACCCGCGGTCGAGTCATGGCGCAATTGCGGCGCGGCTCGATG TTGGCCGTCAGCGGTGACAGCGTTCTGATGCGCGAGCTGATCGCCGATGCGCTCGATTTGGCG GCGATCAACGGCGCTGACCAATTTG-TCTGGAGCGGGCCGAGCGAGGCTGTCCAAGCCGCGGGG DGTCC -GACTGCGCGCCGCCGGCCTGC-GTGCCACCGAGCTGAACACCTCACACGCGTTCCATTCA GCCATGATGGATCCCATTCTGGA-GGCTAACGGTTGCCGGTTCGCGACTTCAGGTCGGTGTC GGGACGATTCCGGTCGTTTCATGCG--TTACCGGAACCTGGTTGACGGCGAAGCAGCTGGCCGAT CCCCACCCCTAGGGGACGGGTCCGGGCACAGT ACAGGGGAGGAGCCGCCGCTGATGCTCGAAGTGGGGCCGGGCTCGACCCTGGCGGCTTTGGCC DCGCGAGCATTCGAATGCCCGCCTCCCGGTCGTCACCAGCCTGCGCCACGCTCGCCAGGCGACG CCCGATCGCCAATACCTGCTCGMXAkCGCTCGGCTGCCTTTGGCGACACGGGGTTTCCGTCGAT TGGGGGGCCCATGCCGGACGTTCGCGACGCTTGGTTTCGCTGCCCGGCTATCCCTTTTCCGGC GCGGTGCGCCGCTTAGCCGGCGACCCCCTCCGCCTGCTGGCCGGAGCCCGCGCCGTCGCCGCC CCGTCGGGAACGCGCCAACTCAGCGCCGACGCGCGCGACCTCCCGACACTCCGGAGCCGACA D CGCCGGCGGTAA"CCATGCCGCACCGCCACCT TCCTGGCGCCAGGCCGGAACGGCGCCGCTCGGTCCGCCCGATCTCGGTCCGCCCCGCGACTGG ATCG TCTTCGCCTCTGATTCTCACCTGCTCCAGGCGCTCAGGGCCAATCTCGGGACGCGCCCT CAGCGGGTGACGCTGGTGACGCCGGGCCAGGAGTACGCAGCCGAGCCGTCCGGGTTTCGGCTG CGGC CGGACCAGATCGACGATTACCGCGCCCTGTGGGCGGACTTGGCGC-ACCGGTATTGTG DCCACGATACATCGCGTTCCTCGCCCCGTTCATGTACCGGGCGCGCATGGCGGGCGATGCCTCG ACCC-TGGACGAAGTGCGCGAGGGCGGCTTCCTGCCCCTGACCCGCTTGATCCAGACTCGCCCG CCAG''GCGGACCGAGCGGACTTCTAAGCCTCACGATCGTCACCCCGGCCGCCCTGGCCCTGGGC GACG-7AGCGACGCGCCCGGAATGGG 'CATCCTGCACGGGATGGTCGCCGGCTTAAGCCGCGAT TATC -CCGAATGGCGCTTCCTCTCGATCGACGGCGGCGACCCATCCCCGCATCGGTGCGAAGGT CTGGCCCGCTTGATCGCGCTTCA7TGCGGTCGACGAGGCTGGCCCGACCCGCTTGGCGCTGCGC WO 00/22139 PCTIUS99/23535 128 GGCCTTCACGCTTGGGTTCCACAGTGCGAGCACGTTCAGCCGGCCACCATCCCTGGGGCGGGT ATGTGGCGCGAGGGTGGTGTGTACATGATAACGGGCGGATTCGGCGGGATCGGTCTGGCGCTG GCCCGCGCCCTGGCTCGAGAAGCTCGCGCCAAGCTGATCCTGGTCGGCCGAAACCTGCCCACC GCGCCGATCGATCTCGAGGCTTGGGACGCGCCGCCGTTGATTCTCACCGCCGACGTCGCCGAC 5 GAAGAGGCCATGCGCCGCGTCTTCGATGCCGCGCACGCCCGGTTCGGCGCCATCGACGGCATT CTTCACGCGGCCGGTGTCCCCGGTGGCAGCCTGTTCGCCAACCAATCGGACGCGGCCTTCGAA GACGTGCTGCACGCCAAGGTTCGCGGTACCCTCGTGCTGCAAGGCCTGAGGGCAATCGATGCG CCGCTGTTGCTGATGTCCTCGCTGGACGCCTGGCTTCCCGGTCCCGGTCAGACCGCCTATGCC GCCGCCAACGCCTTCCTCGACGCCTTCGCCAGTCTGCGCCGGCGAGAGGGAGAGCCGGTGTAC 0 AGCGTTGGCTGGGACAGTTGGTGCGAGGTGGGCATGGCTGCTCGGGTCGCTGCCCGATCGGCC GACGAACGCGGCCGCCTGGCGCGCGAGGGGATCAGCCCTCGCCAGGGTTGGCAGGCTTTGAGC CGGGCGCTCGCCCTCGACCCCCCCCACCTGATGATCTCGCGCACCGACCTGACCTCGCGCTGG CACAGTCGATCCAGCCCTACGCCGGTCGCCTCGAGCGAACCCGAGGTGGCGCTGCCGCGCTGG ACCGCATCCGCCTGCCAAGCCGTCATCGAGCGTGTTTGGTGCGAGCACTTCGCCACCGCCGCC 5 GTGCCTCCCGATGGCAACTTTTTCGAGCTCGGCGCCAGTTCCTTCGACATCGTCCAGCTCAGC GCTCGACTTCAACAACAGTTCGGCCGAGATGTCAGCCACACCGTGCTCTACAGTCATCCCACC GTCGCCTTGCTGGCCGGCTACTTCGCCAATGACCCGACGCCGTCCGGTGCTGCTGCCGACGAA CGCGACGAAGCGGTGCGTCGCGGCCGCGACCTCTTGAAGAGCCGCCGGCGAGGAGTA 0 (2) peptide sequence Seq ID No 62 (>pEPOcos6_ORF11.pep) MTNHDHHEESSGLEIAVISMACRFPGAADCDAFWENLINGTSSITHFSDDELIAAGVDARDLT PQYVRAAGQIDDAERFDAAFFGYSQREAELMDPQFRLLHECAWSCLEQAGIDPRVEAAPIGLY AGAADNTYWNALSSLDRGSAESEQFAAEQLCNRDFLCTLVAAALNLKGPAVVVQSACSTSLLA 5 VHSACRALLTGECRVALAGGVALRFPRPSGYRYEPGMIFSPDGVCRPFDAGANGTVPGEGAGL VALKTLKRALQDGDTIHAVIRATAANNDGARKTGFTAPSAHGQAEVIRTALRLARVPAESIDY VEAHGTGTPLGDPIEVAGLVEAFASEKRGYCRLGSVKSNLGHLDTAAGIAGLIKTVLALEHAH IPKSCHVATPNPAARLHKTPFRIAADGMAWPRRMATPRRAAVSSFGIGGTNVHAILEEAPPPA PELADGRSQVFVFSAKDEAALDRALANYGAALEKRGDLAAGAVAWTLQNGRAAFEWRASAVAS D DLDELAGALRGERPGAVKKNRMAREDKPVAFLCSGQGSQYRGMGHDLYREEPRFRHHLDACLA WO 00/22139 PCT/US99/23535 129 ILAEHKPEIDWLALLGYRDEDEPTDQIGTSSQGPSRSAASNPAELLDSTEFAQPLLFSMSYAL GRLWLDWGVRPTAMIGHSLGEYSAACIADFYALDQVLPFILTRGRVMAQLRRGSMLAVSGDSV LMRELIADALDLAAINGADQFVWSGPSEAVQAAGVRLRGAGLRATELNTSRAFHSAMMDPILE ELTVAGSRLQVGVGTIPVVSCVTGTWLTAKQLADPRYHARHAREPVRFAAGLATLTGEEPPLM 5 LEVGPGSTLAALAREHSNARLPVVTSLRHARQATPDRQYLLETLGCLWRHGVSVDWGAHAGRS RRLVSLPGYPFSGAVRRLAGDPLRLLAGARAVAAPSGTRQLSADARDLPNTPEPTSGAVSAIK APIAAADPGLYRLSWRQAGTAPLGPPDLGPPRDWIVFASDSHLLQALRANLGTRAQRVTLVTP GQEYAAEPSGFRLRPDQIDDYRALWADLAQTGIVPRYIAFLAPFMYPARMAGDASTLDEVREG GFLPLTRLIQTRPPGGPSGLLSLTIVTPAALALGDEATRPEWAILHGMVAGLSRDYPEWRFVS 0 IDGGDPSPHRCEGLARLIALHAVDEAGPTRLALRGLHAWVPQCEHVQPATIPGAGMWREGGVY MITGGFGGIGLALAPALAREARAKLILVGRNLPTAPIDLEAWDAPPLILTADVADEEAMRRVF DAAHARFGAIDGILHAAGVPGGSLFANQSDAAFEDVLHAKVRGTLVLQGLRAIDAPLLLMSSL DAWLPGPGQTAYAAANAFLDAFASLRRREGEPVYSVGWDSWCEVGMAARVAARSADERGRLAR EGISPRQGWQALSRALALDPPHLMISRTDLTSRWHSRSSPTPVASSEPEVALPRWTASACQAV 5 IERVWCEHFATAAVPPDGNFFELGASSFDIVQLSARLQQQFGRDVSHTVLYSHPTVALLAGYF ANDPTPSGAAADERDEAVRRGRDLLKSRRRGV pEPOcos6_ORF12 sequences: 0 (1) nucleotide sequence Seq ID No 63 (>pEPOcos6_ORFI2.seq) ATGACCGTGGAGCACGAAACCGGATTCGAAATCGCCGTCATCGGGCTGGCTTGCCGCGTTCCC GGCGCTGCCGACGTGGCCGCCTTCTGGCGCAACCTGGTCGAGGCCAAGGAGAGCGTGCGCTTC TTCGAGGACCACGAGCTGCGGGCCGCCGGCGTGCCCGAGGAGATCTTGCGCCTGCCCAACTAC 5 GTGAAGGCCAAGCCACTGCTCGCTGATGGCGAAGCTTTCGACGCGGACTTCTTCGGGTTCCAT CCGCGCGAGGCCGCCTACCTGGACCCGCAAGTTCGGCTCCTGCACGAATGTTGTTGGACCGCG CTGGAGGATGCCGGCTACGATCCCGCGCAGTACGCCTACCCGATCGGGTTGTTCGCGGGCGTC TCCAGCAATCTCTCGTTCCTGTTCGACCGCATCGATCCGCGCGACTCCCCCCTGCAGAAGCGC TATGTGGCCGAGCTGAACGCGGCCTCCTTCGCCACCCAGATCGCCTACCGGCTCGATCTGAAG 0 GGGCCGGCCATTTCGATTCAAACCGCCTGTTCGACGTCACTGGTGGCGATTCACCTGGCGGCG WO 00/22139 PCT/US99/23535 130 CAAAGCCTGATCGGCGGCGAGTGC CACATGGCCTTGGCCGGCGGAGCGACCTTGGAGGTCCCC AAAAAGCCCGGCTATCTCTACCGC-GAAGGCTACATCAACTCGCCGGACGGCCACTGCCGGGCC TTCGACGCCGACGCGGCCGGCACCATCTTCGGCGACGGCGTCGGCATCGTCCTGCTCAAACGC TACCGCGACGCCCTACGCGACGGCG--ATCACGTGTACGCAGTGATCAAGGCTCGGCGATCAAJC 5 AGTGACGGCCATCGCAAGGTGTCCT- ACACGGCGCCGGGCAGAGCGGTCAAGTGGCGGTGATC CGCGCTGCGCTGGCGGCGGCCCAGG:TAGAGCCGCAAACCATTCGCTTCGTCGAGGCCCACGGG ACCGGCACACTCGCCGGCGATCCGATCGAGGTAGAGGCGTTGACGGAGGTCTTTGCCGAAGCG GGTCGCGGTACCTGCGCCCTGGGT7-CGGTGAJAGACCAACATCGGCCACTTGGATGTGGCGGCG GGCGTGGCCGGTTTCATCAAGGCGGTCTTGGCGCTCGAGCGGCGCGTCCTCCCGCCCAGCCTT 0 CATCTCGCACCGCTGTTACGCCTTCTTTGCAT GAGCGGTTGACGGAGAACGGGCGGT-TGCGGGCCGGGGTGAGTTCCTTTGGCATTGGCGGCACC AATGCCCACGTGATTCTGGAGGCMZ-'-C'GCCGGCGCCGGAGGCGAGACTGCCGGCCGGGAGCCCG CCAGGCGCGAGTCCGTTCCTGTTr-C CCGCTATCGGCCAAGACGCCGGATGCGCTGGCAGGCCGT TGCCACGACCTTGCCGACCACCTGCGGGCGCACCCCGAGCTCCTCCTGGCCGATGTGGCCCTC 5 ACTCTGCAGATGGCGCGGGCGTCGT TCGCCTACCGCCATOTGGTCCAGGCTGCGACGGCCGAG GAGCTGATTCGCGGTCTGGGAGCG7TCCGACAGGAGTCCATCCGCAGAGGCGGAJATCGAGTA CAATGGGTGTTGGCAGGCGAGGCC-A TGTCGCTTGACGCCGGTTTGCGGCTGTACGCCGATTGG CCGGTCTATCGGGAGCGGGTCGACTCTGTCTGGCGATCGTCGCCAGCTGCGCCATCGAC GGCCGGTCATTCCTACATGAGTGGAzTCGAGCGACCGCGCGAGGTTCCTGCCGAJATGGTCGACG 0 GCGCTGGCGTTCATGTTCCACTGCGCGCTGGCGCAAGCCCTGAGCCAGGCCGGCCTGCACCCG CAGCGCATGTGGAGCCGTGGGCTGGG--CGGACAGGTCGGCGTGGTTTTGGCCGAATCCCTGTCG TTGGAACAAGCGCTGGCGCTGGTG-"TGTGCCAGACACCGGTTCCCGGCGATGCCACACCTCAG CGCGAACGCTTGGTTCGGACACTGC::AAGGCTGCCGGTTTCGTCCACCACGATTTTTGATTTCG GCAGACAGCTCGGGTCGACCCCTGG-1ACCTCGCCGAATTCGCTCATGTCGATTTTTGGTGCGGT 5 GGCCAAAGCGCCTCGCCCAATGAC-3CGGAGCTGCGCTCATGGAGCGACGCCGCGCCCGAGCTG GTGACCTTGGCGATCGGCCCATCCT-TTCTCGAGGCCGCCTCCGGGACGGTGGGTCTGGCGATC GACCCCAAGCGACCGATGACCTG7GTTCAGCGCACGGTGGCCGCGTTGTGGGAATGGGGATGT GACGTGCGCTGGGCTGCGTTCACCTC- -GTCGACCGCGCGTCGGGTTCCCCTGCCTACCTATCCC TTCGTGCGG GTAATTCCCACGATc GG CGACCCCCTTCGCGGAGCAGGCGCGGAGGATGACTTG 0 ATTGCGGCGAGCGCTTCCGCGTCG;"-CCGGATCGCCGCCCGAGCCGTCGGCACTCGGCAGCG WO 00/22139 PCT/US99/23535 131 GAACGCCCACGCGCCCAGTCAAGCATCGCCTCGGCAJACCACACCGGCTCCGTCTCATACGTCG GCCAGCGTGGCCGTGGCCACCATTICTCGAACCGTCCGTGCCTATTTCGGGTTCGCCGCCGTG CGTT-CCACCGACGCCTTCTTCGAATTGGGCGCGTCCTCGCTGGATTTGGTCAACCTGGGCCAG CTCC -TTTCCGATCGTCTCGGCCGCGAGGTTCCGACCCTGCTCCTCTACGACCACCCAACACCG 5GACCAGTTGGCGCTGGCCCTGACATCCGCGGCGCTCAGCGCAGAGGCGCCGCCCTTAAGGGGC GGTCATCGCGCATCGACTTCCGGCACAGCCGCGAGCTCGGCCGCCTCCACCGCACCGACGTTC CCGGGGGACGCTCACTCGCAGCCCAGCTTCGTTCGCGAGCAGGACATCGCCATCATCGGGATG GCCTTCCGGGGACCGGGCGCCGACGACCTGGACGCGTTCTGGACCCTGGTCGAAGGGGTC GAGTCGATCACCTTCTTCAGCGAGGACGAGCTGCTGGCGGCGGGCTCCCCCGCGAJACATCTG 0GCCTCGACGCGCTACGTGCGGGCCAGGGGGAACTGACTGGGATGATGGATTTCGACCGGAA TTTTTCGGTTATTCGGCGCGCGAGGCGGCGGTCATGGACCCGCAGTTCCGCGTGTTCCACGAA TGCT-CCTGGCACGCACTGGAGCACGGCGGCTACGATCCGACCCGATGCGCGGCATCGATTGGC GTCT-ACGCCGGCGTGACCAACCACCTGCCTTGGCTGATGCGAACTTTGCCGCACCTGACCGAG GAGGAGCAATTCGGCGCGCTGCTCCTCACCGACCGCGAGTTTTTCGCACCGCTGCTCTCCTAC 5AAGG7TCGGCCTGCGCGGACCCGCTATTTCGCTGCAAACCGCCTGTTCGACGTCGTTGGTGGCG ATCGGCACGGCCTGTCGCGAATTGCGCGCGGGTGCCTGTCAGATGGCCCTAGCGGGCGGCGTG ACGG-CCAGCATCGAGCGCTGCGGCTACTTCCACCAAIGAGGCTACATCCTCTCGCCTGACGGC CACACGCGCAGCTTCGACGCGGCGGCCGCCGGCACGGTCTTCGGCGACGGAGTCGGCATGGTG CT'GC"-TGAAGCCGCTGGCCCAAGCCTTGGCCGACGGCGACACGATCCACGCGGTGATCAGGGA 0ATC -GGCATCAACAACGACGGCGCGCGCAAGGTCGGCTTCACCGCACCTAGCCGGGCCGGTCAG ACCGAGGCGATTCGGGCCGCGCTGCGCGACGCCGGGGTGGCGTCGAJACCGCGTCAGCTACGTG GAGG- CGCATGGAACCGCGACCAGAATGGGCGACCCGATCGAGGTCGAGGCCTTGACCCAAGCC TTT-CGCGCCGAAGCCGACGGTCCGCTTCCGCCCGGCTCCTGCCTACTCGGCTCGGTGAAGTCC AACGTGGGCCACCTGAACGCCGCGGCCGGCGTGGCTGGTCTGGTAAAAACCGTGCTGGCGCTC 5CAAC-ACCGCCGCCTGCCGACCAGC-CTGTTCTACCAGTCGCCCAATCCACACATCGACTTTGCG GCGAGTCCGTTCCGCGTGAACGGC -CAGACTTCGGATTGGGTCGCGCCAGAGGGGACGCGGTTG CTCGCGGGAGTGAGTTCGTTCGGTLATCGGGGGAACCAACGCCCACCTGATCGTCGAGGAGGCG CCG-AAAGCGCTACCGACGACAGCGG7k:CACCTCTGTCGACGGAGCCGAATGACCTCGACGCGGGC GAC GCCGACGGGCTAGTGCTGCCGATCTCGGCCCGCACGCCGACCGCCCTGGCGCACATCGCG 0 ACC-AACCTCGCCAATCACCTGGAACGACATCCGACCATCGCCCTGGCCGACGTCGCCCTGACC WO 00/22139 PCTIUS99/23535 132 CTTCAGCTGGGCCGTCGCCAATGGCCCCATCGCCACAGCCTGATCTGCCGGAATCGAACGGAG GCGATCAAGCTGCTGCGCGCCGTCGTCCACTCCGCGGAGGTGCCGCCAGCTCAGGCGCCGGTC TCGGATGCGCCGCGCTGTGTTTTTCTTTTTCCCGGCCAGGGCGCCCAATACCCGAGCATGGCC CGCGACCTGGTTCGAAACTGTCCCGACTTCGCCCTGCACCTGGACCCCTGCCTCGACCAGTTG GCCGAACTGCTTCCCGAAGATCCGCGTTGCATCCTGTTCGGCGATGGCCCCGCCGATCGGCTC GACCAGACGGCCTACACTCAGCCGCTGCTCTTCTCCGTGTCCTACGCCTTGGCGCGCTGGTTG GGCGATTTCGGCATTCGCCCCGATGCGATGATCGGCCACAGCCTGGGCGAATACGTGGCGGCC TGCTTGGCCGGGCTTTTCTCGCTGAGCGATGCCCTGCTGCTGGTGAGTGAACGCGGCCGCCTG ATGGGCTCGGCCGCGCGCGGAGCGATGCTGGCCGTCCCCTTGCCCGAATGGGAACTGGAGGAA CGCCTGGAGCTTCTGGCCGACGACCGAATCAGCATCGCGGCGGTCAACACCGCCGAGAGCTGC GTCATCGCGGGACCCAGCGAGGCGATCGAGCGCTGCGCCCAGCGCTGGGCCGCGCAAGGCCTG ACCTGTACGCCGCTGCGCACGTCCCACGCCTTCCACTCCGCGATGATGGAGCCGATTGTCGAA CCCTTCGGCCATGTCTTGGCACGGGTCACCTTCGCGCCGCCGCGCGCGCGCTGGATCTCGAAC CTCGACGGCAAGCCGATCGATTCCGCGGCGGTGATGCAGCCCGACTATTGGGTGCGCCACCTG CGCCAACCGGTCCGCTTTCACGAGGGACTCAGTCACCTGTTGGCCGAGGACACCCATGCTTGG GTCGAAGTGGGTCCCGGCCGAACCCTGTCCTCCTTCGTCCGCCGCCACCCGGCCTACCGTCAC CAGCCAATCGTCAACCCCATGCGCCATGCAGTCGAGTCGACGGGCGACGTGCGCCGGTGGCGC CAAGCGCTGGGCGAACTATGGCGGGCCGGCATGCCGGTCGCCTGGGAGCGGCAGCGGCGCGGC CGGCATGCCGGACGACGTGTGCCGCTGCCGGGCTACCCCTTCGAGCGGCGGCCCTTCGCGGCC CGAAGACCGGTGGAGCTGGCGCAGCCCGCGCCCAAGGCGGAGCTGGTGAAAAACCCCGATCCC GCGCGGTGGCTGTACCGCCGCGTCTGGCGCCCTGCCCAGGCTGCGGCCGGCGGACTGGCGGTG CAGGCGACCGTTCTGGTCTTCGGCGACGGGTCCGAGCTGTGCCGCGCGGCGGTCGCTCAGGTG CAGCGCCAGGGGCTGAAGTGCGTCTCGATCACCGCGGGCCGCCAATTCGCGCGGGAGAGCGAC ATGCGCTTCACGCTTGACCCCGCTGATCCGCGCCAGCTCGACCAGCTCTTCGCGGCCCTCGAT GGC-CTCAGGCTCGCGGCCGCGGTACGTCCTGCACCTGCTGACCCTGAACCCGCCCCCGGATGCC TCGGCGATCATCGCTCACAGCTACTACAGCCCGATGGCCTTGGCTCATGCCTTGGGCGCCCAC GAGATCGCGCCTGTCTCGATCACCGTCGTCACCGCCGGGGTCGTCGCCGTCGCGGACGAAGCG ATTCGCGAGCCGCTGCAGGCGCTGATCGTGGGCCCGTGCCTGGTCATCCCGCAGGAGTTTCCC GGGCTCAGCGTTCGGCTGCTGGACGTCAACGTCGACGATCCGGCACCGCGTCTGGCGGAGCGG D CTCGTGGCCGAGCTCTCGGGCACGGATCACATGGTGGCGCTGCGCGGCGGCGAGCGCCTAGTG WO 00/22139 PCT/US99/23535 133 GCCGATGTCGATCAAGTCGATGGCCTCGGTGTGGGGATCGCCAAGGTGCCCTTGCGCCGCGAG GGCCACTACCTGATTCTCGGCGGCCTGGGCGATATCGGCTACCACTGTGCCCGCTATCTGGCC CAAACCTACCGCGCCAAGCTGACGCTGACCGCGCGTTCGTCACTCCCGCCGCGCGCGTCGTGG GAGCGAATGCTGCGCGAGGGAAACCTGGATTCCCGGCAGCGCACGCGCATCGAGCGCGTGTTG 5 TCGCTAGAGGCGTGCGGGGCCGAAGTCCAGACGGCTGCGGTCGACTTGGGCGATCGCCATCGC TTGGCCGATGTGTTCCGCGAAGCACGGGGCCGATTCGGCGCCATCGCGGGCGTGATTCACTCG GCGGGGATTCCGGGACACGTCCACTCGATCGACGAGCTGGTGCGCGTCCGCGACGAAGCCCAA TTCACCGCGAAGGTTCGAGGGCTGCACCACCTGGCCGAGGTCGTCGATCCGCTGAACCTCGAC TTTTGTCTGCTGTTCTCCTCGCTCTCGACCGTCCTCGGCGGGCTCGGCTACGGCGCCTATGCA 0 GCGGCCAACGCCTACATGGACAGCTTCGCCCGCCGCCACGATCGGCCGGACGAATGTCGTTGG ATCGCGGTCAACTGGGACGCCTGGCTGTTCGAAGCCAAGACGTCGTCGGTCGGCGCCGAATTG GCGCGCCTGGCGATCGTGCCCGAGGACGCTCCGGCCCTGTTCGCGCGGGTGCTAGAGCGACTT CCGCAATCGTTCATCGTGTCCACCGCCGACCTTCGGGCCCGCATCGACACTTGGATCCGGGAC AAGAACCGCGTCCCGCCCGCCGAGATCCGAGCGGTTCAACCGCGACCGGACCTGAGCCAGGCG 5 TACGCCCCGCCGATCGGCCCGCTGGAGATTCAACTCTGCGGGCTGGTCTCCGCCTATTGCCGG TTCGACCGGATCGGGCGGGACGATTCCTTCTTCGAAATCGGCCTCAGCTCGTTCGACTTGATC CAGCTCAGCTCGCGCATTCACCGCATCACCGGCAAGGATCTCAATACGACCCAACTGTTCAGC TACCCCACCGTGCGCGCCTTGGCGCTCTTCCTCGGCGGCGAACCGGAGGGGCTCGCGGCGGAG GAGCCCGCCATGGAGAACCTGTGGCTGCAACGAAGCGATGCGACCCTCGATGAG 0 (2) peptide sequence Seq ID No 64 (>pEPOcos6_ORF12.pep) MTVEHETGFETAVIGLACRVPGAADVAAFWRNLVEAKESVRFFEDHELRAAGVPEEILRLPNY VKAKPLLADGEAFDADFFGFHPREAAYLDPQVRLLHECCWTALEDAGYDPAQYAYPIGLFAGV 5 SSNLSFLFDRIDPRDSPLQKRYVAELNAASFATQIAYRLDLKGPAISIQTACSTSLVAIHLAA QSLIGGECHMALAGGATLEVPKKPGYLYREGYINSPDGHCRAFDADAAGTIFGDGVGIVLLKR YRDALRDGDHVYAVIKGSAINSDGHRKVSYTAPGKSGQVAVIRAALAAAQVEPQTIRFVEAHG TGTLAGDPIEVEALTEVFAEAGRGTCALGSVKTNIGHLDVAAGVAGFIKAVLALERRVLPPSL HFVRPNPAIDFNGPFYVCRQIERLTENGRLRAGVSSFGIGGTNAHVILEEAPAPEARLPAGSP 0 PGASPFLFPLSAKTPDALAGRCHDLADHLRAHPELLLADVALTLQMGRASFAYRHVVQAATAE WO 00/22 139 PCT/US99/23535 134 ELIRGLGAFRQES IRKRRNRVQWV LAGEAMSLD)AGLRLYA]DWPVYRERVDVCLAIVAKLRQTD GRSFLHEWI ERPREVPAEWSTALAFMPFHCALAQALSQAGLHPQRMWSRGLGGQVGVVLAESLS LEQALALVLCQTPVPGDATPQRERL-VRTLEGCRFRPPRFLI LADS SGRPLDLAEFAHVDFWCG GQSASPNEAELRSWSDAAPELVTLAI 'GPSFLEAASGTVGLAIDPKRPMTCVQRTVAALWEWGC 5 DVRWAAFTSSTGRRVPLPTYPFVRV TTPTIGDPLRGAGAEDDLIAASASASAGSPPEPSASAJ ERPPAQSSIASATTPAPSHTSASVAVATILETVRAYFGFAVRSTDAFFELGASSLDLVN~LGQ LLSDRLGREVPTLLLYDHPTPDQLALALTSAALSAEAPPLRGGHRASTSGTAS SAASTAPTF PGDAHSQPSFVREQDIAT IGMAFR-:DGADDLDAFWNNLVEGVESITFFSEDELLAAGVPREHL ASTRYVRAKGELTGMMDFEPEFFGY--SAREAAVMDPQFRVFHECSWHALEHGGYDPTRCAS IG o VYAGVTNHLPWLMRTLPHLTEEEQ-FG-ALLLTDREFFAPLLSYKVGLRGPAI SLQTACSTSLVA TGTACRELRAGACQMALAGGVTAS IERCGYFHQEGYTLSPDGHTRSFDAAAAGTVPGDGVGMV LLKPLAQALADGDTIHAVT KGIGTN',NDGARKVGFTAPSRAGQTEAIPAALRDAGVASNRVSYV EAHGTATRMGDP IEVEALTQAFRAF---7ADGPLPPGSCLLGSVKSNVGHLNAAAGVAGLVKTVLAL QHRRLPTSLFYQSPNPHIDFAASP--RVNGQTSDWVAPEGTRLLAGVSSFGIGGTNAHLIVEEA 5 PKALPTTAAPLSTEPNDLDAGDAEL'JVLPI SARTPTALAHIATNLANHLERHPTIALADVALT LQLGRRQWPHRHSL ICRNRTEAI KLLRAVVHSAEVPPAQAPVSDAPRCVFLFPGQGAQYPSVA RDLVRNCPDF'ALHLDPCLDQLAEu_-PEDPRCT LFGDGPADRLDQTAYTQPLLFSVSYALARWL GDFGIRPDAMIGHSLGEYVAACLLFSLSDALLLVSERGRLMGSARGAMVLAVPLPEWELEE RLELLADDRI SIAAVNTAESCVIA-PSEAIERCAQRWAAQGLTCTPLRTSH&FHSAMMEPIVE o PFGHVLARVTFAPPRARWI SNLDG---{2'-IDSAAVMQPDYWVRHLRQPVRFHEGLSHLLAEDTTAW VEVGPGRTLSSFVRRHPAYRHQP:-- JNPMRH-AVESTGDVRRWRQALGELWPAGMPVAWERQRRG RHGRPPYFRPARr EAPPALKPPRLRVRAAAGA QATVLVF'GDGSELCRAAVAQVQRQGLKCVS ITAGRQFARESDMRFTLDPADPRQLDQLFAALD GSG-'SRPRYVLHLLTLNPPPDASA: :-AHSYYSPMALAHALGAHEIAPVS ITVVTAGVVAVADEA 5 IRE?--LQALIVGRCLVI PQEFPGLSV.RLLDVNVDDPAPRLAERLVAELSGTDHMVALRGGERLV AD-VDQVDGLGVGIAKVPLRREGHYL I LGGLGDIGYHCARYLAQTYRAKLTLTARSSLPPPASW ERM'LREGNLDSRQRTRI ERVLSLEAC- -GAEVQTAAVDLGDRHRLADVFREARGRFGAIAGVI HS AGI PGHVHS IDELVRVRDEAQFTA-VRGLHHLAEVXDPLNLDFCLLFSSLSTVLGGLGYGAYA AAIAYMDSFARRHDRPDECRWIAN7\WDAWLFEAKTSSVGAELARLAIVPEDAPALFARVLERL 0 PQS F--IVSTADLRARI DTWI RDKNRV::.PAE IRAVQPRPDLSQAYAPP I PLE IQLCGLVSAYCR WO 00/22139 PCT/US99/23535 135 FDRIGRDDSFFEIGLSSFDLIQLSSRIHRITGKDLNTTQLFSYPTVPALALFLGGEPEGLAAE EPAMENLWLQRSDATLDE pEPOcos6_ORF13 sequences: 5 (1) nucleotide sequence Seq ID No 65 (>pEPOcos6_ORF13.seq) ATGAAATACGAAACCACCGGATTGGAATTGGCCGTCATCGGTCTCGCTTGCCGCTTTCCAGGC TCACCCGATCCCGAACAGTTCTGGTCGAATCTGCGCGCAGGTCGCTCCGGAATCCGCCATTTC 0 AGCGATGCCGAGCTGAGCCACATCCCCGCATCCCTGCGTCACCATCCGCATTACGTCAAGGCC AAAGGCGCGCTGGACCACGCCGATTTCGAACCAGCCTTCTTCGGCTACTCGCCCAAAGAGGCC GAGGTGATGGACCCTCAATTCCGGCTGCTCCATGAGTGCTGCTGGGAGGCGCTGGAGTCAGGC GGCTATGCGCCGAGCCAATTCGCGGGTCGGATCGGCTTGTTCGCGGCGGCGGCCTTCAACGAC GGATGGATCGCCGGTACCCTCGACCGGCTGCGCACCGGCGTGGGTTTGAGCTCCCTGGAAACC 5 GCGTTCTTGACCCTGCGCGATTACCTGACCACCCAGATCTCCTATCGGCTCGATCTGCGGGGC CCCAGCCTGCTTGTCCAAACCGCCTGCTCGTCGTCGCTGGTGGCGGTCCAGCTCGCCCAGCAG GCGCTGATCTCCGGCGAATGCGCCCTGGCCTTGGCTGGCGGCGTGTGCGCGACCGATCCGCTG CATTCGGGATACCTCTATGAACCCGGCAACATCTACGCGCGCGACGGCGTCTGCCGACCGTTC GACGAGGCAGGCGCCGGTACGGTCTTCGGCGACGGGTGCGGCATGGTCCTGCTCAAGCGGCTG D AGCGACGCCCAGCGCGACGGCGATACGATCTGGGCGGTCATTCGCGGGGCGGGCGTGAACAAC GACGGGCACCACAAGGTTGGCTACACGGCTCCTGGCACGAGGGGCCAGGTGGCTTTGCTTAAA AGTGTTTATCGCGCGAGCCGGGTCGACCCGGCGACGCTCGGCTACCTGGAGGCCCATGGCACC GGCACCGCGCTCGGCGATCCAATCGAGGTCGAGGCGCTTACCCAGGCCTTCGCCAGCAAACGT CGCGGCACCTGCGGCTTGGGCTCGGTCAAGGGCAACCTGGGTCACCTCAACACGGCGGCCGGC 5 ATCGCTGGACTGATCAAGGTGGTGCTGGCGCTGAAACATCGCGAAGTGCCACCCACCCTCAAT CTGCGCCGTCCCAATCCGAAAATCCGCTTCGACGAGACGCCGTTTTTCCCAGTCGTCGAGTTG CAACCCTGGCCAAGCGGGACCGGCCCCTTGCGAGCCGGCGTGAGCTCCTTCGGCATCGGCGGT ACGAACGCCCACGTCATCCTCGAGGAGGCACCGCCGACGGCCAACCCGGCGCCACACGGCAGA TT C CGACTGTTGCCGCTTTCGGCCAAGACACCGGCTGCGCTCGAAGCGAAGCGCCGCGATCTG ) GCCGGCTTCCTCGAACGCCACCCGGAGACCTCCTTGGCCGACCTCGCCTTTACCCTGCAACGC WO 00/22139 PCTIUS99/23535 136 GGCCGCGAGGTCTTCAGTCACCGCGCCTGCCTCGCCGTGGAGACCTTAACGTCCGCGCGCACG CGGCTGAGCGGCGAGTCGTCGAGCACTTGCGTGGTGGGCCCCGCGCCCAGCGCCATATTTCTG TTCCCTGGTCAAGGCAGCCAGCTCGCCGGGATGGGCCGCGGTCTGTATCACCATTTCGAGCCG TTCCGCACGGCCGTCGATGCCTGTCTGCGCGAGCTGGAGCCAGGACTGCGGCAAGCGCTCAGC 5 GCCCATTTCGATCCGAATCGCGGCGCGGACCCACCCGATTCGACGACCTTCGTCCAACCCTTG TTGTTCCTCGTCGAGTACGGGGTGACCGAGTGGCTACGCTGCTTGGGTGTGCGGCCAACAATG GTGTTGGGTCACAGCTCTGGCGAGTATGCCGCAGCCTGCGTCGCGGGCGTTCTGTCGCCGTCC GCGGCGGTCTCGCTGCTGGCCGAGCGCGAGCGGCTGCTGCGCGACCTGCCAGCCGGCGCCATG CTCGGCGTCCCGCTGGCCGCCGAGGCGCTCGAGGCGATGTTGCCCGACGCTCTCGATCTGGCG 0 GCGATCAACGGCTGTCAGCTTTGCGCCGTGTCCGGGCCGGTCGCGGCGGTCCACGCCTTCAAG GCCCAACTGGAAGCCGCCGGACATCACGCCCGCCTGTTGCACACCGATCGCGCCTTCCACTCG CGGCTGGTAGCACCGGTGCTTGACCGGTTCCAGGCAGCCGTTCAACACGTGGAGCTGCGGCGG CCGCAAGTACCTTACCTCTCGACCGTCAGCGGGCGATTGGAGGCGGATGGGCCGGCGAACCCG CACTACTGGGTGCGTCACCTGCGCGACACGGTGCGGTTTGGTCCAGCCCTGGAGGCGCTGCCG 5 CCGGTGGATTCCTTCGTGTGCATCGAGGTGGGACCAGGCTCGGCCTTGAGCACCATGGCGCGC GAAACGTTGGGTTCCCAGGCGCGACTGATTTCGTTGCTGCCGCGGCCGCGAACGGGGCAAATC GAGCCCGGTCCGGTATTCGAACGACTGGCGGCGCTTTGGCGCAGCGGGTTGACATTGGATTGG TCTAAATTGACGGGCGGCGAAGAGGGTCATCGAATTCCCTTGCCAGTCTACCCGTTTCAGCGC AGCCATCTGTCGAGCTCCCTGGCGGCGGGCCACACGCCTTCGTCGCGGCCTGCAGTCGAATCA 0 GGCGCCATCCTTGCCGAGCGATCCGCAGGGGAAAACGCTGAAACCCGGGATTGCCCGCTGCCA ACCGCCACGCTCGAGCCCAAGGCGGTCGCTCCGGCCCCACTCGAGGCTACCGACGCCGCAGGT ACTCGCGAGCGACTGGCCGAACTTTGGCGCGAGTTGCTAGGGTTGACCTCGATTGGGCCCGAC GACCATTTCTTCGACCTGGGCGGCCACTCGCTGACCGCCACGCGGCTGCGCGCCCTGATTCAC CAGCGGTTCGATGTCGATCTCGGGCTCGACGAAATCTTCGCTCATTCGCGTCTCTCCCAGCTG 5 GCCGCCCGTATCGAGGCGGCGGCCAAGAGCCGATTTTCCTCCATTCCCAGCGCGCCGGACCAG GACGACTATCCCTTGTCATCCGCCCAGCAGCGGATTCACAGCATCGTCACGAGGGCCGAGGTC GGCACTGCTTATAATTTTCCGATCGTCCTCGAGCTGCAGGGCGCTCTGGATCGAGTGCGATTC GAGGCGACGTTCGCGGCATTGTTCCGGCGTCATGAGGGGTTCCGCACCCGCTTTGTGATGCGC GATGGCGGGCCGCGCCAGCGCATTGTACCGGACGTGGCGTTTCGCCTGCCGCTCACCCAGGTC 0 GAGCCAGAGCAGGTTCCCGGGCGCATCGAGGCCTTCATCCGTCCCTTCGATTTGGAACGCGCG WO 00/22139 PCT/US99/23535 137 CCGCTGTTCCGCGCGGAGCTGTTGCAGTTGGCCGAGCAGCGCCATCTGCTACTTTTCGACATG CACAACTTAATTGCCGACGGTATCTCGCTCPJACCTGTTCGTCGCCGATTTCGCGGCCCTGTAC CATGGTCGTCCGCTGGCGCCGCTGAAACTCCGCTATCGCGACTATGCCGTTTGGCAJAGAGGCG CGGCTGGCCTCCGATGACCTGCGCAG.'CCAGCGCGAATGGTGGCACCGGCGGCTTTCGCCGCCG GTCGCCACGCTGGCGCTCCCTCCCGATTTCCCGCGTCCGGCGGTGCGCCGCTACAAGGGCCGT AATGTGGTGTTCCACCTGGACCGGGAGATCCGCGACCGCCTGGTGGCCCTGGCTCGAACCCAG GGGGTCACCATGAACGTGATGATGCTGGCGCTCTGGGCTGCGCTGCTGCATCGCGAAACCGGC CAATCGGAGCTGGTGGTCGGATCGCT.GCTCGGCGGGCGGCCGCACAGCGAGCTGCATCCCGTG ATCGGGCTCTTCACCAACTTTTTGCC-CTTGCGGTTGGCGGTCGAGGGATCGACCCGCTTCGAT CGCTTCCTTGCCGCTTGCCACCAGGTG0TTTCTCGAJAGCCTATCAGCGCCAGGACTATCCGTTC CACTTGTTAGTCCAGGAACTCGTGCC GGTCAGGGACCCGTCGCGGTCGCCGCTGTTCCAGACC TCCCTTCAACAATAGCAACACGATGAGGTAAT GAGGTCCTGAAGTTGGGCGATGACGAGGCCTT TCCGACCGACTCGAATGTGTTTTGCAATACGACTTGGATCTGTTCTGCGAGGAGACGATGCGC GGCCTGATCGCGCGGTTCCAGGCGTTGGTGGCGGGGCTTGTCGCCGATCCGGCGCAJATCGCTC GCCGCCGCGAGCGTTTCCGGGAAGCGGCGCTGCGCGCGGGCGTGGCCACGGCAJGCGAATCG TCGCCGCAGTCACTGCCGCCGCAACCATCGACGGCGTACGCCACTCCCTCACCGCAGTCACCG TCGCCGGTAGTCCTGACGGGACCCGC -CGACCTGCCCGCGATCTTGGCGGCCTACGTGGGGCAG AACCCCCATCCGTTCGCGATCCATC, GGGTCTCATTTTGGAGGCGCCGCTGGGGTTGCGAGCG CTGCGGTCGGCGCTGGACGCAGTGC -TCGGAGAACACACCCATTGGCGCAGCGTGCGTGCGGGC GATCGCGCGCGGCGCGTGGATAAGTT-GGM&TTGACCAGCCTGGTGCGGCTCGACGACCTGCGC GGGTTGGTCAATCCTCAGGCGAATGC -CTTCACCCTGGCTTGGCGCGATCTGGCGATGCCGTTC GGGGAGGGGCGTCCCCTGTGGCGACT CCGCCTGGCGTGGTCGGCTCCATCGCGCTGGTTGCTA TTGCTGACGGTTCATCCATTGATCGG -'CGACAACGGCACGGTCGACCTCTTTCTGGCGGCACTC GCCGATCACCTGCGCCGCGCGTCCGC -TTTTCCCGTAGCACCGCTCGATGAGGCCGAGCTGGAG GCGGAGCTGAAGTGGGGAGAGGAAC-GGGAGGGCCTCGGGCTGACCGCGATCGCGCCGCTCCTG GGCCAATTGCGCGAAAGTCGGCTGAG:TCCTGTGGCCCAGATGTGGCTGGACGAGGTCTGTCGC CGCCACGACCTCACCCCGCTAGAGCTCTTGGCGGCCCGGCTCCTCGATTGGACACGAAGCCAC GGTCACGGGTCGATCGCTTTGTGGACGCCGCTGCCCGAGGACCATCCGCTTCGCGATGAAGGC CGCTGCCTCCAGGTTCGCCTGCTGG :AGGGGCCGCCGTCGCAGCGAGGAGCGGGCGATCCAAGC WO 00/22139 PCT/US99/23535 138 TGGCTCGAGCAAATCGCCTTGAGACGGGGTACCCCTGCAACGGAGGTCGTTTGCCCTACTCCG ACCCAACGGGCAGCCATCGACCTCGCGCTGGCCTGGCTGCCGCAGCCGCCTCTTCACGGTTTG GTCGGAACCGTTCAGCCGTGGCCGGAATCTCCATTGGTCTGTCCGTTTCCCCTCAATCTCGCG TTCCGGCCAAGCCATCCAATTGCCTACGCGCTCAAGCACGAGGCCACGCTCGCGGTCACGGCA D CGGGCGCGCGATCTGATGCGTTTCCTCGACGGCTTGGGCCCGGAAAGC (2) peptide sequence Seq ID No 66 (>pEPOcos6_ORF13.pep) MKYETTGLELAVIGLACRFPGSPDPEQFWSNLRAGRSGIRHFSDAELSHIPASLRHHPHYVKA KGALDRADFEPAFFGYSPKEAEVMDPQFRLLHECCWEALESGGYAPSQFAGRIGLFAAAAFND GWIAGTLDRLRTGVGLSSLETAFLTLRDYLTTQISYRLDLRGPSLLVQTACSSSLVAVQLAQQ ALISGECALALAGGVCATDPLHSGYLYEPGNIYARDGVCRPFDEAGAGTVFGDGCGMVLLKRL SDAQRDGDTIWAVIRGAGVNNDGHHKVGYTAPGTRGQVALLKSVYPASRVDPATLGYLEAHGT GTALGDPIEVEALTQAFASKRRGTCGLGSVKGNLGHLNTAAGIAGLIKVVLALKHREVPPTLN 5 LRRPNPKIRFDETPFFPVVELQPWPSGTGPLRAGVSSFGIGGTNAHVILEEAPPTANPAPHGR FRLLPLSAKTPAALEAKRRDLAGFLERHPETSLADLAFTLQRGREVFSHRACLAVETLTSART RLSGESSSTCVVGPAPSAIFLFPGQGSQLAGMGRGLYHHFEPFRTAVDACLRELEPGLRQALS AHFDPNRGADPPDSTTFVQPLLFLVEYGVTEWLRCLGVRPTMVLGHSSGEYAAACVAGVLSPS AAVSLLAERERLLRDLPAGAMLGVPLAAEALEAMLPDALDLAAINGCQLCAVSGPVAAVHAFK D AQLEAAGHHARLLHTDRAFHSRLVAPVLDRFQAAVQHVELRRPQVPYLSTVSGRLEADGPANP HYWVRHLRDTVRFGPALEALPPVDSFVCIEVGPGSALSTMARETLGSQARLISLLPRPRTGQI EPGPVFERLAALWRSGLTLDWSKLTGGEEGHRIPLPVYPFQRSHLSSSLAAGHTPSSRPAVES GAILAERSAGENAETRDCPLPTATLEPKAVAPAPLEATDAAGTRERLAELWRELLGLTSIGPD DHFFDLGGHSLTATRLPALIHQRFDVDLGLDEIFAHSRLSQLAARIEAAAKSRFSSIPSAPDQ D DDYPLSSAQQRIHSIVTRAEVGTAYNFPIVLELQGALDRVRFEATFAALFRRHEGFRTRFVMR DGGPRQRIVPDVAFRLPLTQVEPEQVPGRIEAFIRPFDLERAPLFRAELLQLAEQRHLLLFDM HNLIADGISLNLFVADFAALYHGRPLAPLKLRYRDYAVWQEARLASDDLRSQREWWHRRLSPP VATLALPPDFPRPAVRRYKGRNVVFHLDREIRDRLVALARTQGVTMNVMMLALWAALLHRETG QSELVVGSLLGGRPHSELHPVIGLFTNFLPLRLAVEGSTRFDRFLAACHQVFLEAYQRQDYPF D HLLVQELVPVRDPSRSPLFQTSLVYHNEIDGKTKLELEGLKVEVVPFEKGVARLDLKLDVTPF WO 00/22139 PCT/US99/23535 139 SDRLECVLQYDLDLFCEETMRGLIARFQALVAGLVADPAQSLAAASVSGKRALRAGVATASES SPQSLPPQPSTAYATPSPQSPSPVVLTGPADLPAILAAYVGQNPHPFAIHRGLILEAPLGLRA LRSALDAVLGEHTHWRSVRAGDPRARRVDKLELTSLVRLDDLRGLVNPQANAFTLAWRDLAMPF GEGRPLWRLRLAWSAPSRWLLLLTVHPLIGDNGTVDLFLAALADHLRRASAFPVAPLDEAELE 5 AELKWGEEGEGLGLTAIAPVLGQLRESRLSPVAQMWLDEVCRRHDLTPLEVLAARLLDWTRSH GHGSIALWTPLPEDHPLRDEGRCLQVRLLEGPPSQRGAGDPSWLEQIALRRGTPATEVVCPTP TQRAAIDLALAWLPQPPLHGLVGTVQPWPESPLVCPFPLNLAFRPSHPIAYALKHEATLAVTA RARDLMRFLDGLGPES 0 pEPOcos6 ORF13.1 sequences: (1) nucleotide sequence Seq ID No 67 (>pEPOcos6_ORF13.1.seq) ATGACGCAAGCCTCGGCCGCGTCGACGTCCCAGGTCGCGCCGGAGGTCACCCCCGGCCGAAAG 5 GACGACGATGACGATCAAATCCGAGATGTCGGCCGTTGCTCACTCTGCGGAGAGCGGCTTCCG CGCTGGGCCACGCGTGGGCGGCGCGATGAAGCGGGGCCGGACGCCGGAGCAGGCCGGCGTGAA GCTGCTCCGCGCCCCGGTGAAGCGGAAGTGGCTGCCCCCGGCGCCCGTCCTGCGCCTGAGCGA GCGGCGTATCCCGGAGGTGTGGGCAGGCTACCGCGCGAGCGCGGGATGACCCGAGCCCCGCCC GCCGGCGCGACCATGACGCCGCCCCACGGGGCGAGTCGTCCGGCGCGCCGGCGCGCGTCGGGG 0 CTTCCGCCGCCGGGCGGGCAGGTGCAGGATGGTCGGGCATGG (2)peptide sequence Seq ID No 68 (>pEPOcos6_ORF13.1.pep) MTQASAASTSQVAPEVTPGRKDDDDDQIRDVGRCSLCGERLPRWATRGRRDEAGPDAGAGRRE AAPRPGEAEVAAPGARPAPERAAYPGGVGRLPRERGMTRAPPAGATMTPPHGASRPARRRASG LPPPGGQVQDGRAW WO 00/22139 PCT/US99/23535 140 pEPOcos6_ORF14 sequences: (1) nucleotide sequence Seq ID No 69 (>pEPOcos6_ORF14.seq) 5 ATGGTGACGCGTCCGACGTCCGACGGCATCGAGGACGAGCTCGCGCCGTTCCCCCCGGTCCTG CGCGGCTGGCTCATCGAGGGCGAGCTCGGCCGCGGCGGGATGGGGCGGGTGTTCCGGGCGCGG CACCCGAAGACGCGGGCGCGGGCGGCGATCAAGGTGCTGCTCGGCGACTACGCCCGCCGGCCG GACGTGGTGGCCCGCTTCCGGCAGGAGGCGATCGCCGTCAACATCATCAACCACCCGGGAATC GTCCGCGTCTTCGACTCCGGCGAGCTCGAGGACGGCTCGCCCTACATCGTGATGGAGTACCTG 0 GACGGCCGGGGGCTGCGCGACTGGGTGCAGGCCGTGCCGCCCGCGGAGCGGCCGCGGCAGGTC GTGCGGCTCGGCTACCAGATCGCCTCGGCCATGGCCGCGGCGCACGCGTCCAAGGTCGTCCAC CGCGATCTGAAGCCGGAGAACATCATGGTGGTCGAGGACGAGCTCGCGCCCGGGGGCAGCCGC GTCAAGATCCTCGATTTCGGCATCGCGAAGGTCCTCTGGGGAGGTCTGCCCGAGGTGCTGGAG CTCGAGGGGAGAGGCTCCCTCGCGCCCGCGTCCGCGTCCACGATCCGCACCGAGCTCTCGACG 5 CGGCCGGCGCCGACGGTGGGCGCCACGACCGGCCCAGAGAGCCCGCTGGGCGCGAGCGCCACG CCAGAGAGCGCCCTGGGCGCGAGCGCCACGCCAGAGAGCGCCCTGGGCGCGAGCGCCACGCCA GAGAGCGAGGCCCACGAGGAAGACGCGCTCCGGAGCCTCCCCGTCGTGACCAGCGGCAGGCCC GCGATCCACCCCGCGCCGGTCGAGATCCCGCCCGAGGCGGTCTCCTCCGCGGCGTCGCGCGGG TCGCGCGCGTCGATCGAGCCAGGCGCGCCCGCGCCGCAGAGCGAGGGCGCGGGACAGCCCACG 0 ATGCCGTTCACGCAAGAGGGCGTGTGGGGCCTCGGGACGAGGAGCTACATGGCGCCGGAGCAG GAGCGCCACTCCGGGAGCGTGGACGTGAAGGCGGATGTCTACTCGCTCGGCGTCATCCTCTAT GAGCTGCTCGAGGGGCGGACGCCCGACGCGCCGAGCGCCGCGTGGCCGCCCCCGATGAGCGCC GCCACGCCGCCCGATCTCGTCGCCCTCGTCCACCGGGTTCTGGCGTTCGATCCCGATGCGCGG CCGCGCATGGCGGAGGTGGCGAGCGCGCTTCACCGGCTCGGCCGGGCGAAGAAGGAGCTCGAC 5 GAGGCGCTCTCGAGGTGGGTCGTCGGCGGAGGGGCGCCGGGGCTCTTGCCGTGCGGCTATGCT CTTCTCGAACTGGTCCTCCTGGGCCCTGGGAACTTATACGATTCTTTCCAGCCTGTAAGTGCA TTTTTCTTTCAATATCGTCCTCTCTTCATATACGAGGTGAGTTCTCTGAGGTCCTCCTATAAG TCTGGGGTGTCCTATTCGGCCTCTTACTTGTTACTTCGCCTTCTTAGGAGTTTTTCCTTAATT TTGCCCTCTTACATTCCCGTATTCATTCTAACTGGGCCCTATCTCATTCGC 0 WO 00/22139 PCT/US99/23535 141 (2)peptide sequence Seq ID No 70 (>pEPOcos6_ORF14.pep) MVTRPTSDGIEDELAPFPPVLRGWLIEGELGRGGMGRVFRARHPKTRARAAIKVLLGDYARRP DVVARFRQEAIAVNIINHPGIVRVFDSGELEDGSPYIVMEYLDGRGLRDWVQAVPPAERPRQV 5 VRLGYQIASAMAAAHASKVVHRDLKPENIMVVEDELAPGGSRVKILDFGIAKVLWGGLPEVLE LEGRGSLAPASASTIRTELSTRPAPTVGATTGPESPLGASATPESALGASATPESALGASATP ESEAHEEDALRSLPVVTSGRPAIHPAPVEIPPEAVSSAASRGSRASIEPGAPAPQSEGAGQPT MPFTQEGVWGLGTRSYMAPEQERHSGSVDVKADVYSLGVILYELLEGRTPDAPSAAWPPPMSA ATPPDLVALVHRVLAFDPDARPRMAEVASALHRLGRAKKELDEALSRWVVGGGAPGLLPCGYA 0 LLELVLLGPGNLYDSFQPVSAFFFQYRPLFIYEVSSLRSSYKSGVSYSASYLLLRLLRSFSLI LPSYIPVFILTGPYLIR, or DNA sequences complementary to said open reading frames, 5 (b) DNA-sequences which hybridise under stringent conditions to regions of DNA sequences according to (a) encoding proteins or to fragments of said DNA sequences, (c) DNA-sequences which hybridise to the DNA-sequences accord 0 ing to (a) and (b) because of a degeneration of the genetic code, (d) allele variations and mutants resulting by substitution, insertion or deletion of nucleotides or inversion of nucleotide 5 segments of DNA-sequences according to (a) to (c) , wherein the variations and mutants offer isofunctional expression products.

10. DNA sequence according to any of claims 1 to 5, wherein the DNA is selected from the group consisting of 0 WO 00/22139 PCT/US99/23535 142 (a) the following DNA Sequence: Seq ID No 71 (>Contig43) CGGGTATTTGTGATATGTGGGCNGTAGTCGTATGCTTCATTAAGTACATC 5 CGTCCGTNGTAGAGAGTGACTCTGTCGCAGCGATAATAGACACGCTTGTG ATGCTATAGGGAACATAGAGTCNTAGTAGATGATACGACGAGATATTNGT ATAGAGCGTATAGACCGACGTGTGAGCGTCATAAGTGTTGTGTGTCATGA GTGTGCTCAGAGGACGTGCAGACATTATATGAGCAGATGATGAGAGAGAA TCAATGCTGCAAGNTATTCGTCGAATCTACATTATATCGAATCGTGTATG 0 TGCGTTTGTCGCAGCGCGATNCGATGAGATACCGAAAGGGTATGTATCTA TNTTCGTGACGCTCGATNAGAGCAAATCCGCTACCGTGGAGATATCGTGT ATCGACTCCATCACGATCAGTATCATGATACGTCAAACGAGTACACTCAT TATTGATAACACACGTANGTGTGCATGCACAGTTATCGAGTGTATTGTGT GCATGAGAGGTATAGGATNTATAGGCGAGCATATATATCTATATATATAG 5 GTTAAGAGTAGAANACTATGAAGATGCAGGAAGTAGTATCTCGCGGACAA ACGGNGTACCTAGCGGGGTTGAAGTATTATCGACAGTGTATAACGACTCA ACAGGNTACGAGGTACATTGTATTTACAGTGGTTGGAAGGATTGCGCGA GGAAAGGTAGTGGTACCGTGTGAGC-TACGATGCTCGGGATAATGGTGATT AGATAGAACCTTAGCGTTGCTAGATGAGTGAGTGGTGGTATGAGTAGAGT 0 TTTTGTTCTAGCTTTGTGTCCAGCGAGGATTCGTTCAGTCTGAAGGGTAA GAGTACGTCCATCGCACACCCGACCGTTTTGAGGAGTTCTCGGTGCGTGG TCAGTGGGGTTTGGAGAAGACAGAGTTGATTCATAGGGTTATCAAACGAG TTATGTGGATAGATGGTAGTGACCCCATTTGAGTGAGAGTGTTGGCGTTA ACANCAGCAGGATNTAT 5 SEQ TD No 72 (>Contig44) TAG G:CTTTGACACCATGGGAGCTGCTACCGATGTTGCCGAGCACGATCG CGCC 3GCGCCGACGAGCGACTGCAAGCCGGCCGCGGCCATTTACGCCTGA CGAGCGAGGTGGGCGAAGTGCTGGTGCGCGCCGTGCGTGTCGAGCGCGCC 0 CAGGTCCGCCGTTGCGCCGTCGCCGAGCAGTAGCGCGCCGTCGAAGACGA WO 00/22139 PCT/US99/23535 143 TCACCGCGATCGAGGTCAGCGTCGTGGGGGCGAGGCCGAGGAGCGCGAGG ATGCCGAGCACGACGCCGGCCGCGCCGTAGACGAGCTTGGCGCCCATGCC GCCGCCGAGCTCGGTGCGCGTGTCCCACTCGACGGGCGGCGCGGTGCGGC TCAACGCGCCGAAGCGCGAGGCGATCGCGCCGCCCTGCGCGATCAGCGCG 5 GCGCCGAATACGATCGTGGCGATCTGAGGTGAGCTCTACTGGCATGATCC CCGTCAGCCCGAGGATGGTGAGGACAATCGTCGCGGCGCCGCACAGTACC TCGCACGAGCGAGCCTCCGAGCACGACCTTCGGCGTCGTCTCGTCCTTTG GTCTGCGTCGCGCGCCCGAGTGCGGCGTTATGTGGCTCTCCGGCTGTGCA AACCGTTCACGTTCTTCCGGTCCTGGAGTCAGCATCGGCATGATTCCCCC 0 GTCCTGCGGTGAGGCCTTGTCGCGCTCACGCGCGCTCCGACTTGCACGTG CTGTGCCGGGTTCTCTCGCTCAGGAGGCGCCTCTCTTGGTGGTGCTTGCG TCCTGGTCCGTTTGCCCGCCTGTGCGGTAGGTTTCTTGAACCAGGTGACC TTCAGGGACCCCTTGATGCGCTCCATCGTGTCCTATGTCGATCCTTCTCT GACTTGTATGGGTCTCGAACCAACTACGCTTGATCAGGCCTTCGAAGGGT 5 CCTTTGGGAGATCGACTCTGGATCCATACCGGGAGCCCCTGTTCTGCCGC TCTCTTAAGTTTCCCCTTCTGTATCCGTGTCGACCGGAAACGCTTTATCT CTAATGCGCTCTAATTGCGTCTCTGCCACACGTGCGCTTCACTCTGGATC TACTTCTTCTCCCTAGTCTTCTACCTCCGTACCCTTATTTGTTGGTTCTA TTTATTTCTTTTCGCTTCACCTCGCGTCATTGTCGCCTAGTGTTCCTCCC 0 TCATATCGCCTTTGGTCTCCCTCGAGCGTACAGTCCTCTCTCTTCAGATG CTTTCCGGCTCCTCTTCTGCTGGCCCCTTATCCTTTCTAATACTTC SEQ ID No 73 (>Contig48) ATGCGCCCAGGAACACCCCGGTGCGGCTGCCGTCGAGGGACTGGGGTGCG 5 ATGCCGGCGTCCTCGAGCCCTTCCCAGGTGACCTCCAGCAGCAGGCGTTG CTGAGGATCGAGCGACCGCGCCTCCCGAGGCGAGGTGCCAAAGAACGCGG CGTCGAAGCCGTCCACCGCCTCGGTGAGCAGTCCGGCCCAGCGCGGCACC TC ?TCGCTGGGATGGACGCCGACCAGCGCCCAGCGCCGGTCGAGCGGCTG GACCGCGTCTCGGCCTGAGTCGAGCAGCTCCCAGAATGCCTCCGGAGTGT 0 CCGCTCCGCCGGGGAAGCGGCAGCCAATGCCTACGATGGCGATCGGCTCG WO 00/22139 PCT/US99/23535 144 GTCCGCTCTTGCTCCAAAGACGCGTTCTTTTTCGCAAGCTTGTCCATGAG CAGAAGGGCATGCTCAAGCTTCCCGGCATTCGTGGTCGCCATACTCCCTC GGTCCCTTACTCACCAACGATCTGCGCGAGCTGCGCCAGCTTTTCGGCGA GCAACGCGTCCTTCTGCTCGTCCGTCATGCCCCGCAGAGCCTCGAGATCT 5 GCGGCATCGTTCTCGAAGCTCTTCTCCCGCTCGGTGGCCGGAGCGTGGGT CGCGCCGGCATTCGGAAACAGAATGTCTAGCAAGCTCCCGCTCAGAGCTG CTACGTTAGGGTAGGTCCATAGCAGGGTCGCCGGCACGGTGATGCCGAGC GCGGCCTCGATGCGGTTGCGGAGCTCCAGGCCTATCAGCGAGTCCATGCC GAGATTGCTGAACGGCACGTGCCGCTCGATCCTCTCCGGCGGAAGGCGCA 0 GCCCCCGCCCCAACAGCTCGCTCAAGTGCTTCTCCAGAATCAACTGACGA TCTTCGGGCCTGGCGCTCTGCAGCGCCTCGCGCAGGTTCGACGCGTTCGA CGCGCCTCGGTCGGCGCGGTCACGCTCCTTCAGCAGCTCCGCCCACAGCG CCAATCGGGCCGCGTTGGGATAGAACTC 5 SEQ ID No 74 (>Contig49) ACCACCGCTTCACTCAGTATGTACTTTGTTATACTCGTCTTAGTACAATG ATATAATACTCATGTGTATTCTTAATCTCGGGGAGANAAAATTGGAATAC TGGACACCGTTGCCGCATGCNGACTCTAGAGATCCCCCTGCGACGGTATC CCACGGCACCGGTATGGCCGGCGCGCGCTCCGGGGGTCAACGCCCCGTGG 0 TTGCCTTCACGACAACGCCGGTCGGGCGGGGCGCCGTTCGATGCCGCGGG CCCGCGCGCGGCGGCGCGTTATCCTGTGGAGCATCTGGAGGGCGCTCACG CACCTGTCAGTCTAGTTCTGGCCCGCCCGGAAGGAGTCCGGGAGGCCGAA GTTGAACCCGATGTAGAGCGCGATGAACGACGGGAGCACGCGCGCGGGGA TGTGCAGCGCGGCGCCGATCGGCGTCGCGAACAGGACGAGCTCGCCCGGC 5 ATGCCGGGCACGACATACCCGAGCAGAAACACGATCGGCACCACGAGCGT GAGCTCGAGCAGCGATATTTCATGACCGACCGCGCGGGCGGCGGCGCCCG CCATGACGAACACGCAGATCAACGTGCCGTTGACGTTGAGCCAACCGCCG AGTCCCACCACGAAGAGCCTGAGCTCCTGCGGCACCGCCGGATAACATTT GCGGACGAGGTGCAGGTTGAGCGGCGTCGCCAGCGCCTCGCTGCACGAGG 0 CCCACAGCAGCGGATAGACCTTGAGCCAGTAGTTGACGAAATAGTCGCGC WO 00/22139 PCT/US99/23535 145 AGCGAGAACTCCGGGGCGGCGGCC--7CATCCGCAGCAGGCTCGCCGCATG GAAGACGAGGCAGGCAGCGCCGACGAC CC CGGACACGAGCAGATAGGAGA GCATGAGGTCTCCGGCGCCGAGCGAGGGCGCCCCCGCCGAGGCGCGCGCG AGGTCCCCCCCGTGCACCTGCGCGGC -GAGCTGCGCGGGCAGCCCGCGGAG 5 ATAGGCGCCGAGCCCGAACATGAAC--AGCGGGACCAGGCACTGCACGGCGC CTCCCGCGCGCTCCAGCGCGTCCCG GCGCGCTCCAGCGCGCGGGCGACC CGCGGCGCGCGTACGGCCGCGACGACGTCACGATGCCGGCGTAAAGGGC GAGGAAGCACGGGCTCGAGATGAC CAGGCCCGAGGCGCTATAGAGGGTGC GCGCGGCCTCGAACGGCGCGCCCG'7CTGTGGCTGGGGAGCAGCGGCAC 0 CCGAACACGAGCCATGTGACGACGAC-CCCGAACAGGCACGCTGCCAGACG CTTGAGGGCGAGCCAGCCCATGAT 3?:-ACGCGAGCAGCCGCCCCGGGCGCC CTTGCCGGTGCAGGCTCACGAAG-z GGCACGAGGACGACGAAGATGACG ACCGGCGCCAGCGTGGTGTACCAA-7GCAGGAGACCGTCCATGGCGCGGGT CGACCACCGCGTGACGCTGGTCTCTC'- -TGTCTGACTCGATCATGGCCCATT 5CGCCTAAAACTAATGATCCGTTCTCATTGGTCAAAAAGTTCCCTT AAGACTGTTTTACTCCGGAATATTAATATATTTCTGAGTGTGAGGTGATG TTAATCACACATTCTGATATTCT C72AGGGGAATC CGTGTCATTGTGAATA CTTCTCTCTCTACAAGAGAGGTTAT-ATATGGTCTCGAATATCTCGTCCGC TCTTATATATATTCTCTTGTGATA7TTTTGGGTGTCCG 0 TCTCTTGGTGTAATCTATAACTCG-GCATCTCTCATAATACCTTATATATA CACACTCTCTCGGTCATATCTCGCAT -AATAGATATATTTTATATGTTCCG CGTTTTATCCGAGTGGGATACAC---:T TTCTATATTTTCTTTGGTGTGACG CGTGGCGTCGAGCCTTATTATTGTTTGGTAGTCACGATATTCTCTAGAT GACATCATACAGATGCTCATAACT CG,-ATAAACACAGGTCGTACACGACGA 5GACTCTCACTCTCACTCTT SEQ ID No 75 (>Contig5(C TCCCC 'AGTTTCTCCTCTCTACGCCC--aC -ATCTCAGCAGGAAAAAAJATAAT GGAGAATCGTLTGCGCTCTAGCAGCA TCTATAGGATCCCCGCTGCTCTTCT 0 TCATGCACCTCCTGGAGCAGAAGT'C--ATCAACGCCTTCGCGATCATCGTG WO 00/22139 PCT/US99/23535 146 CGCGTGAGCTTCCTGGCGTTGCTCCTGTCGCTCGTCGTCGCCGACGTCC GACGCGGAACACGTTCCCGCCCGCGCCTTTGCCGGCGCTGAGCCCGCCGG CGCC-GGCGCTGATCCCGCCGGTGCCGGGCGGATCCGTTGGGCCGTCGCCG GAGCCGCTGTCGGTCGGCCGGTGATCGGTTGTGCGGGCGCCGTGCCTCGG 5 GCTTACTACCCCCTCTCGCGGGTGGGGATATGGCCGTGGATGAGGGAGGC GATGAAAATCGTGATCGCCACGTGCGCGTTGTTCTAGATCGTCCCAGGCT GACCGTCGGGAGCGCCCAGCACGAGATGAAGAGCCACACCGCGAGGACCG TGT:-GAGGTACCGCACCGCAGGGGCGAGCATGGCGGTGATCGCGAAGATC ATGCAGAGCAGCCCGAGCACCCATGTGTTCGTCCGCTGCGCGTGGCTGTG o CGGC-CAGATGACGGCCGAGATGAGGAGCCAGAJACCCGAGGACGACGTTCA CGA7I'CGCGCCATGAGATTGCCAGCTCAACCATGCTCCCTCCCACCTCC GAT CATGGGACCGATCGGGTCGCCACGGATCGATAAJCGGGCGTCAGGAGA CCGT CAATCGGCGAGCTCGTGAGCCATGGCGACAGCCCGCCGACCGCGCC GGCGGGTCTCTGGCCTGCTGGTCGCCGTGCCGGCGGCGGCGATGGGCCTG 5 CCTC--CGGTCGGGCCGCGCGGGCGCGCGGCGCTCCGCGCGAJAGCTGGAGAC GCGGGACATCGCTCCCTCGCCCCGCGCTCGGACGAGCGGCGCGAGCCACT TCTCGACGGCCGAGCGGGCACTAAGCTTCCGTCATGAGGCTCGGCGCACG GC7TCACCACGCACACGTTCTCGGCCGGCGCCGCCGGCATCAGCTTCGTCG TCCAGCCGATCCCGGGCTCGGACCAGCTGTTCGTCATTCCGATCCAGTAC 0 CTGCZ-TCGCGGCGTCGCTCGCGAAGGAGCGAGGCGCGCCGCTCTCGAAGGC GGC3--TGGTCCCAGGTCCACCAGCTCATCTGGGGCGGCGGCGCGCTTCGCC TCA7TGCTCGGCTTGACCCTAGGGCTGATCCCGCTGGCCGGCGCGTTCACG AACG-CGATGACGGCGTTCCTCACGACCGAATATCTCGGGTACTACGTGGA TAG AGCCCTCGACAACCCGGACAATCCGCCTCCGGCCCTGTCGATCCAGG 5ATG:C- -TTGGACGCCr-ATCACCTCCTTCTTCACCGGGCGAGCGCGCTAGGCG AGC3GTCCCTGGGTCGAGCCCACCCTGCGGCTCTAGGAGCCGAJAGGGCGA GC:CCTCGGGAGCGGCGCGGCGTCACCACCAGATTCGCCGGCGCTTGCGG CC-5-AGCGTATCGCGACCGCCGCCACCGCCGCCACGGCGAGCACGGTGAC CGC 3-GCGGCCGCCGCGATGGCGACGCTCCGGGCCGTGTGCTCGGCCTCGC 0 CCZCG ATGCCGCCCCACCTCGCCTTGACCGTGACCAGGTCGCGCGCGAGC WO 00/22139 PCTIUS99/23535 147 CGCTCCTTGCTGTGCTCGATCTGCTCGGCAGGCCCCGCGGGCGCCACGAA ACCTGCGCCGGCGCTGACGTGACCTCGCTCGCTGAGGGGACTGGCGACCC TCTCCGTGTCGAACCGGATTGCGCTGGATGGATCCATATGTCCCGCGCTG CAATCGTTGCTCCCCGCCGGCACATCGGAGTGCTCGCCGGATCGCGCGGC AGCGCCGACGCCGTACTTCCATAGGATAGCCCACCCCATCGGACAAGCCG GCTCCTGACGGCGGGCACCGAATGTTCGCCAGACGGGCACAAGGCGCACG CCGCGGACGGATCGGCCGCACTGGCACTCCAGAGCGCATCGACGGATGGC CGACGGATGTGCAATGAGGCGCCCGCACGAAGCGAATTGTCCCGAATACA GCGAAGAAATCTATAGCGATGCGAGCAGAAGGATATGTCTATGGGGGGCA GTCAGAAACTGGGGACAGTCAACGCACATATTCTCTCCAANTGCTAACGA CAGCGTGCGCAGAGGAAGTATCCTACTAGTGTAAGAGGGACATTCGATGC GACCGCATAAACATTCAGTCTACAACGCGTGAGAGGATGGAACACCCCGC CCCTCTGAAGGCTAGACAACCATGAATATGTGCAGAGGAAACACAGAATT CCAAAGGTGAGAACATATGTAGGATCGCGCCACCCGAGATTGAGTGAAGA TATACATATATACTTATATGGATCTACAACATGGCGAACCGAACGTAGCA NAATAGTAGATATAATTGTAATACTGAGCTACCGACAGAAAGATACACAC GAGTGTACACACATCACACGCAGAGTGGTACCAAATTCACACCATGCGAG CCACAATGTGACACGGAGGAGCACAGCATGGGCGCCACTATGGAGGAGAA ACTACTGCAACCCACATCTGATGGACTGACCGCACGGACGGGACGTGTCT ATACATACAGATACATCNGATGGAGGAAGATGCATGTGCGATGATATCAT CGTCGCAAACTCATATGTCGAAGAAGATATGNGTCAACTCAGCACTACTC ACACGATACGTGAACAGGAGTGACTAGGACATCNCATGGTGTGTCGGCGC GTGCACGTGATATCAAACTCTCTGATCAACCACACACTATATAAGGAGTA TCGAGCGGCGATGGAACACCCCCTCACAGCATACGTATATGCACAACGTC TGAACACTCTNGAGACACAGTGGAAGG SEQ ID No 76 (>Contig5l) GATCCAGTTACGCCCCGCCGCCTCGGTCACGCCGGGGTTTTCGGCGTCGA CCGGGGACGGTCGGGGCGACAACCGGGGGTTGTCGTCAGCGGTTCGCGTG GAT YTGCGCGACGAAGTTGTCCGCCGCCGAGTCGTCCTGCGTGCCGCCGC WO 00/22139 PCT/US99/23535 148 GCTGCCGTACGAGCAGCCCGAGGCACCGCGCGAGCTCCTGCCGCTTCCGA TGCGCGGCGGCCTGCTCGGC CTCGT7GCTCCGCGATTCGGCGCTGGCGCCT GCTCTCCTCGGCGCGTTCCTGCGTCC-GCGCGAACAGCACCTCCTGCACCT CCGCGAGTTCCTCGGCGGTAGCGACC CGCACGTGATCCGCACGTCCTCCG 5 AGACCGGTGACGACGTCAJACCGCGGAGTAGTACGCCTCCGCGCGGACGAC GTCGTCGAGGTCGAGTTCAGCGTCGGCTCCGACGACCAGGCGCATCGCGT CGGAGGTGAGGACGACGCCACCGTCG--AGCGGCGCGGCCTCCGGCTCGTAG ACGTACTGGAGGTCGGTCTCCTCG-- CGTCGTCACCGTCGAGGTCGACGTG CCGCCGCAGGCCTCGGGTCCACTCGATCGCGCGTCGTCCGGCGAGGGCTT o CCTCGTACTGGGCCCACCACGCGCGCAC--ACTGCTTCGGCGTGCCGTAGCCC TCGGCCATGTCGGGGTCGAGCCCG-GC GACCTCGATGTCCCACAGTCGGTA GAGGATCTGGAACGGCGTCATGGACT--TCCGGCCCCGGCCGGTCTTGGAGT CCAGACGGGCGGTCTCCATCGCAGCTGCGCCGGCGGCTTCGAGGTCCTGG TCGACGGAGTCGGGCCGCTCTCGCTTCCCGTCCTGGTTCTTGGTGAGGTA 5 CTCGATCAGCGCGACGTCGTCAGCTGjACCGGACGATCGAGACCATCACGC CGTGGCCCTTGCCCTTGCACTTGCAGCCGGGGGTGTCGCAGTCGGTCGAG GGCTCGAACTTGGGGTCAGCCCGCT TGAGGGCGCCCGCCCACATCTCCCG GAGCCAGTCCTCCCAGTCCCCCAGG,"TCCGTCTCGGAGGGCTCAAAGTGTC CGACGACGTCACCCTTGGCCGGGGTG -'CCAGAGAGCTCGCCGCCGAGGAAG 0 ACCAGCAGGTTGAGGTGGGGGTGGTACCGTTCTTCTTGGACCGGGTGAC CTCAGCCGCGCGGACCATGCCGArnGTAGCCGATCCGGTGGCGGATGCCGT CCTCAGCGGGACGGACGTACTGCGTTCCGTCCTTCCGGGTGCGGCGGGCC TCAGGGCGGCCGTAGAAGGCCGGGGCCGTGAGCATCCGCTGGTAGGCACC GGGCGCGCGGCGGGGCTTGCCCGACCGGTCGAGGACCGGGGCGCCCTTGT 5CGTCCAGGAGAGGCCCGCCCCAGAGCGCGGCGACCAGGCTGTCGAGGTCG GTGGTCTGGTTATGCCGGGCGGTGAG-:GACGACAACGGCGAGCGTGCCGCC GGCGGCGAGGTGCCGCAGAGCACCGG '-TCTTGATCTCCTCGGTCCGGCCAC GGCGGATCGCGGAGGAGCACTCCGG-GCATA CCAGATCCGCCCGCAGCGG ACCAGGCCGATCGTGACGACGTAC C C -- ACGCC TCGACTTCGCCTAGATCAC 0 GCC GGTGTCCGGGTCGAGGACCCGUCCGCCCG-CACCCGCCGCAGG-CGTCGA WO 00/22139 PCTJUS99/23535 149 TCCCGGAGACCCGGTTGAGCACCT-TG-CGGCCCTGGTAGCGGCGTACGGCA GCGGTCGCCGCGCGCCTTGTGGTCT GTTCCGAAAGGGCTGCCGCCCTCTC GGACTCTCCCGTTCCTCCCACGACTLGCCACTTCCGCAAAGTCGCTGGTCA GTGGGGGGTGGGAAAACTCTGTCAA CCCTTTACCTAGGCGTCCCTTTTTG 5CCAGGGGCGGTCTCACGGGCGGCCTCGGCGGCTCGGTCGGCGGCCTTCCG GGCCCGCGCGGCCCGCTTCTTGCACGCCTCGGAGCAGAACTCCTTGGCTC GCTTGCCGGGGGTGATCGTGAGGG\CG GCGCCGCAGCGGCIAACGGGGGCCG GCGGGGACGCGGGCGGGCGACTGACTCGGCCGCCGATCAGAGGGGGT TGCGGACGCCAAAGCGTCCCTTACGCCTGGACACAGACGAGTACCTTGGTT 0 GGTAGCCGGGTGGACGTCAGAAGC GG-TCAGGGATTAGGACCCCTGGCCGT TTCGCTTTTTCTGGAGTTGTTCGGTAGATCCTGCCGCATCGCCCGCCTC ACGCGTGGCTCGCCGCGCGGATGCC-TCAGAGGCCCCACCGGTCGTCAGGA CGCAGACGTCGGCGTGCTCCTGGTLGG-:TGAGTCACCAGCTCGACCACACGG GCGCGG C CGGC GAC GTCT C SEQ ID No 77 (>Contig52) CGGGATCTGGCCTTCATTAACCAACG-ACGGGGCAAACATAATAGGCTGGG CATTGCGCTTCAGCTCACCACAGCCC-GTTTTCTGGGAACATTTCTGACGG ATTTAACTCAGGTTCTGCCTGGTCTTCAACATTTTGTCGCGGTACAGCTT 0AATATCCACCGTCCAGAAGTTCTCTC-CCGCTATGCTGAACGGGACACTAC C CTTAGAGAACATACTGCATTAA-TAAGGAATATTACGGCTATCATGAJAT TTGGTGATTTTCCATGGTCTTTCCGC CTGAAGCGTCTGCTATATACCCGG GCGTGGCTCAGTAATGAGCGACCGGG -TCTGATGTTTGATTTTGCCACTGC ATGGTTGCTTCAAATAAGGTATTACTGCCCGGAGCACCACACTAGTAC 5GTCTCATCAGTGAAATTCGTGAAAGGl GCAATCAGCGGCTGTGGAAAJ.AG CTGGCCGCACTGCCGAACAAATGGC-AGGCAGCTCAAGTGATGGAGCTTCT GGTCATTCCGGAAGGTCAGCGTGT ATCAGCACTGGAACAGTXXXXXXXXX XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXGCTGGAACGATAT ATCCGATTACGAAGTCTTGAGTTT--CCCGACTGAACTTTTCCGGTCTCC 0TGCCATTCAACTGCGTAATCTGGC--CCTTATGCTGGCATGGCGTCGGTA WO 00/22139 PCTIUS99/23535 150 AATATATCGCTCGAATGCCACAGCAGAGAAAGCTTGCTGTACTTACTGCA TTCGTTAAAGCACAGGAAATAACGGCATTAGACGATGCCGTTGATGTGCT TGATATGCTAATTCTGGACATTATCCGCGAAGCAAAGAAAACCGGGCAAA AAAAAAGACTCAGGACACTGAAAGATCTTGATCAGGCCGCATTGTTACTG 5 GCGCGGGCATGTGCATTGTTGCTGGATGATAATACAGATGTCCCAGATCT CAGGCAGGTTATCTTCAAGTGCGTACCCAAAAACAGACTGGCAGAATCTG TAAGCAAGGTTAATGAACTTGCTCGTCCACAGAACAXXXXXXXXXXXXXX XXXXXXXXXXXXXXXXXXXXXXXXXXXAAACGTTTTCTTCCGGCGGTGTT GCGGGACCTGCATTTCCGTGCGGCACCGGCAGGTGAACATGTACTGGCTG 0 CGATTCATTATCTGGCAGAACTGAATGGTTCGAAAAAGCGCATCCTTGAT GATGCGCCTGAACATATTATCACCGGTCCCTGGAAACGCCTCGTATACGA TGCGGAGGGACGGATACAGCGTGCAGGTTATTCACTATGTTTGCTGGAAC GCCTTCAGGATGCACTGCGCCGCCGGGACATCTGGCTTGAAAACAGTGAT CGCTGGGGAGATCCTCGCGAGAAGTTGTTGCAAGGTGAAGAGTGGCAGAC 5 TCAGCGTATTCCTGTCTGTCGGGCACTGGGACATCCTGTCGATGGACGTA AAGGTGTGCAACAACTGGCTATTCAGCTGGATGAGACCTGGAAAGCCGTG GCATCACGATTTGAAAAGAATGCGGAAGTTCATATCTGTAATGAAGGTAA ATATCCATCCCTGACTATCAGTTGTCTGGAGAAACAGGAAGAGCCACCAT CATTGCTTCGTCTAAATAATCGGATCAAACAGCTACTCCCACCGGTAGAT 0 TTAACGGAACTGTTACTTGAGATAGATGCCCAGACAGGATTTACACATGA GTTTGCGCATGTCAGAGAATCTGGTGCTCGAGCGCAAGATTTGCACATCA GTTTATGTGCGGTATGAATGGCTAAGCCCTGTAATATGGGCCTGAACCCG TTGATAAAGCACAATATACCAGCATTGACCCGCCATCGGCTCAGTTGGGT GAAACAGAATTACCTTCGTGCAGAAACGCTGGT 5 SEQ ID No 78 (>Contig53) ATTCCACGCGCTCACGGTCAGCTTCGACCCGCGCGAGCGCCCGGCGGCCG CCTCGCAGAAGCGCGCGGTCACGCTGTCCGAGCTCGGCGCGGACGCGCAG GCGCCGGAGTGGCCGTTCCTCGTCGGCGACGAGGCGGCGACCCGCGCGCT 0 CGCCGAGGACCTCGGGTTCCGCTACGCCTACGATCCGACCACCGATCAGT WO 00/22139 PCT/US99/23535 151 ACGCCCACCCGGCGGCCGTCTTCGTCCTGACGCCGGACGGGCGGATCTCC CGGTACCTGTACGGGACGGAGTTCCCGGCGCGCGATCTCCGGCTCGCGCT CCTGGAGGCGAGCCGCGGCGGTATCGGCACGATCGTCGATCGGGTGATCA TGACCTGCTATCGCTTCGACCCGGCGAGCCGGAGATACGCTCCGTTCCTA 5 CTCGGCTTCCTCCGGCTCGGGGCGGCGGCCATCCTGATCACGGTCGGCGG GCTGCTCGCCGTCCTGTGGCGGCGCGAGCGCCGGCGGCCAGGTGCTCGCA CGAGCGCCGCCGTCGGTCGTGACGCCGTGGCCGACCGCCAGGGGAGGTCA CCATGATCAACGAGCTCCTGCGCAAGCTTCTTTTTCTGTCCGGCCAGTGG TCGACGATCGTGTTCGACATTTACAAGCTGCTTTACTTCGTGATCTCGGT D GACGATGGCCGGCGCGACGCTCGTCGCCCTGTTCGCGGCCTACCTGATGA TCCGGTACCGCAGGCGCCAGCGGGATGTTGAAGGCCCGTTCCCCGGAGCG ACCGCGAGGCCTCCGCTCCTCCTCGAGGTCGGCATGGTGCTGGGCCTCAT CGTCCTGTTCCTCGTCTGGTGGGTCATTGGAATGCGGCAGTATGCAGAGC TCCGCGTCGCCCCCGCGGACCCGGTCGTGGTGTACGTGACCGGGAAGCAG D TGGATGTGGAAGTTCGCCTACCCGGAGGGCCCGAGCTCGGTGGCGACGCT CTATGTGCCGGCGCGTCGGCCGGTGAAGCTCGTCATGACGTCCCGGGACG TGATCCACAGCTTCTTCGTCCCCGATTTTCGCATCAAGTACGATGTCGTC CCCGGCCGCTACACCACGCTGTGGTTCGAGGCGACCGCGCCGGGCGCCTA TCAGATCCTGTGCACCGAGTACTGCGGGACGAACCACTCCACCATGCGCG D GCGAGGTGATCGCGCTCGAGCCCTCCGATTTCGCGCGGTGGCTCTCCGAC CGCGGGCGGGGCGCCGGTATCGCCGGACAGGAGTACACGCCGCCGTCGAC GCCGGGCGAGGGGATCCCGCGCGAGCCGCTCAGCCTCGTCCGGCTGGGCG AGAACATCGCGGCCGAGGAGGGCTGCCTGCGCTGCCACACGCCGGACGGG ACACCGCACATCGGGCCGACCTGGGCCGGCCTCTACATGTCGGTCGTCCC D GCTGGAGAGCGGCGGCGCCGCGGTCGCCGACGACGCGTACATCACCGAGT CGATGATGGATCCGCTCGCCCGGATCCACCGCGGCTACCAGCGGGTCATG CCCTCGTTCCTCGGCCGGCTCCAGCCGGCGCAGGTCGCCGCCATCGTCGA GTACATCCGGTCGTTGAGGGGCGTCGCGCCGGAGCCGGGCGCGCGGACGC CGCTGCCCGAGGGCCCGCCCTTCCTGCGCTCCGGCCCGGAGCGCCCCGCC CCGCTCAGCGGGGGCGCGCCGGTCGGCCCGATCGAGGGCGGCAAGCCCGG WO 00/22139 PCT/US99/23535 152 GGAGGAGCTCCGATGAGCACGGAA'-CGTACGATCTCTGCCCGACGCGCC GGCCGAGAGGCCCGAGCCCCGACT:-tCCTCCATGTTTACCGCGGGGTGACG GAGTGGCTCACGACCACGGATCAC:; AGCGGATAGGTCTCATGTTCTACGC CGTCATCCTCGGGAAAGCTTCTTC CTCGGAGGCATATTCGCCCTCATCAT 5 GCGGACCGAGCTCCTCACGCCCGA 3-GGACCATCATCGACGCGGCGACCT ACAACCGGATGTTCACGCTGCACG'ZCr-GTGATCATGGTCTGGCTGTTCATG ATCCCGTCGATCCCCAACGCGTTC'-G-CAACTTCGTCCTGCCGATCATGCT CGGCGCCAAGGACCTCGCGTTCCC C CGGATCAACCTCGCGAGCTTCTACA TCTACCTCCTCGGGGCGGCGATCC CGATGGGCGGCATGATCGCGGGCGGC o ACGGACACCGGCTGGACGTTCTAC CCGACGTACAGCCTGAAGACGCCGAT GACGCTGTTCCCGGTCGTCTTCGG---ZsTCTTCATCGTCGGCGTCTCGTCCA TCATGACGGCGGTCAACTTCATCG7GACCACGCACACGATGCGCGCCGAG GGGCTCACGTGGAGCCGCCTGCCG CTCTTCGTCTGGAGCACCTACGCGAC GAGCATCATCCTGCTCTTCGCGAC CCCGGTCCTCGGGCTCTCGATCCTGC 5 TCATCGGCATCGACCACGTGACCGCCCTCGGGATGTTCGATCCCCGGTTC GGCGGCGATCCGGTCCTCTTCCAGCACCTCTTCTGGTTCTACTCCCACCC CGCCGTCTACATCATGATCCTGCCGG"CGTTCGGCGTGGTGAGCGAGGTCG TCTGCACGTTCGCGCACAAGCGCC OCGCGTCCTACTGGGCGATCGCCATC TCGTCGCTCGGGATCGCGTTCGTGCZGGTTCTGGACGTGGGGCCACCACAT 0 GTTCGTGGCGGGGATGAGCGAGTA-CG-CCGCGGACGTCTTCGGCGTGCTCT CGATGTTCGTGGCCATCTTCTcCGGC CATCAAGGTCTACACGTGGGTCGCG ACGCTGTACAGGGGCTCGATCCAC--TCAACACGCCGCTGCTCTACTTCAT CGCCTTCCTCTTCCTGTTCGTCrT C3GGGGGATGACGGGCGTGGCCGTCG CCACGCAGTCGCTGGACGTGCACC CG,-CACGACACATACTTCGTTGTGGCG 5 CACTTCCACTTCATCATGGTGGCCQ- GGACGCTCACCATGTTCCTCGCGGC GGCGCACTACTGGTTTCCGAAGAT C-TTCGGGCGCCTCTACTCGGAGCGCG TCGGGCTCCTCTCGGCCGCGTCGG :S,TTC CTCGGCTTCTTCTTGACCTTC TTCCCGCAGTTCCTCCTCGGGAACA'-!TGGGGATGCCCCGCCGCTATTACAG CTACCCGCCGCGCTACCAGTGCCCCACGTGCTCTCGACCGGCGGCGCCT 0 ACCTGCTCGCCGCGGCGCTCGTGATC--TCGCTCCTGAACCTCGTCATCGCG WO 00/22139 PCTIUS99/23535 153 CTCAAGTGGGGCCGGAAGGCCGGGAGGAACCCCTGGGGCGGGCGCACGCT CGAGTGGATGACCGGCGAGCCCTTG-CCGCCCAAGCACAACTTCCCGGTCG CGCCGCTCGTCCGCCGCGGCCCGTAC-GAGTTCCAGCTCTCCGAGGAGGAC GCCCGTGCGACAACCACGCCCGCTGC-GTGAGCAGTTCGAAGATCTCGAGA 5AGCAGACGCACGCGGCCCGCCTCGG-GATGTGGTTGTTCCTCGGGACCGAG GTGCTCCTCTTCACCGGGCTCTTCGC-GCTGTACGCGGCGTACCGCGAGCT CTCCCCATCCGGCATGGAACAGCCAC GCACCACCATGACGCTCATCCTGATC-GGCAGCAGCTTCACCGTCGCCATG GCGGTGCACGCCGTCCGCGCCTCCCACCCGCGGCGCGCCGCGCTGTTCCT DCGCGGTGAGCGTGGCGATCGGGATCCTGTTCCTCGTGCTGAGGGATCG AGTACGCGCAGCACTTCCGCGAGGG7-CATCTTCCCGGCCGGCGCCTACCGC TTCGCGGAGCTCCCGACGTTCGGCGC-GCAGATGGCGTTCACGCTGTACTT CGCCATGACGGCGCTCCACGCCCTGCACGTCGTGGGCGGGGCCGGCCTCC TCACGGGGGTCGCGTGGGGGTGCTG,-:AGGGC CGGTACTGGGCATACGAC DCAGACGCCGGTGGAGCTCAGCGGCCTCTACTGGCACCTCGTGGACATCAT GTGGATCTTCATCTGGCCGCTCCTC-TACCTGACGCGCkJAGTGACGGCACA GCCCGGAGACGACCATGCCGCAAGAG -CACGTCGCGGAJAAGCACGCCCTGG ACCCGTTACCTCATGGACGCTGATGGCCCTCATTGCCCTCACGCTCCTGT CGTTAGCGCTCTCGTTCTTGCGCAC GGGGGCTTGGGAAATACCGATCGCG DCTGCTCCTCCCCGTGGTGAAGAGCGT GCTCGGGCTTGCTTTCTTCTTGCT CCG-TC -GAGGTGCATTAAGGTCATCAACGCCTTTTTCACATTGGCTGC TGGTLGTACTTACTTGGACGTTTCAT-ACTGTCTCTTTTATGGCCCCCAACG GTCATTACGTCGACCTACACAATTIC -TCTTCCCGCACCCTCCTACCTGTA TCTCTAAGCACTGCCTTGCGTCCTGC-TCTATTACATTCTACTCCGGCTGT DCCATGTGTGGGATTATATGCGCGAGaGTACCTATTCCGCCGTGGAGTCTCC ATTTLACCTCTTGGACCTTGCCCGTTC-TGAATCTCGATCTCCTCATGCGTT GGTC -CACCATGTATTACCTCCTAGAATCTTATACTCCATATCTCTATATA TCTAGTTGTG-CGTGTAATTGTGTC -ATATATTATCGCCACTGCTGTATGAA TACCGTGCCGACGTGCTATATAC-AAA2NTACTCCTCGGTCGATATCTCCA DCCTCATATATACCTCCGAGTGTAGT,-ATACGCACGAGTGTATATACTCTTC WO 00/22139 PCT/US99/23535 154 CTCTGGTCACGCGACTTCGTGCTGATATGATACCATCGTTCCATGTTACG CGAAGTTACTCATAAGATCTCCTCACACATCAACGAGTGTACTCCTATGT GTTTCATACAAACTCGATACCCTTCAGAGTAGTGTCATGCCTATGTGGTA TGCATAATGTTAGTATACTTT 5 SEQ ID No 79 (>Contig54) TGGGAAAGAGGGCCACAGGGGATGTAGCAGGACGCTTAATAGTAAATGAC GAGGGTGTGCCGACGAGACCCGTAGGAAACAACGGGCACAGACGAGAGCA ATAAAGGGGGTTGGAAGGTACCCCGGATAGAGTAGAGAAGGCTAGCGGAC 0 GAGTAAGACGCGGAGGAAATAAGTCGGCGTCGTAGAAGTTCTGTGGAGAA GGTACGACTCTTAAAGACCTAGGCGGGAGACAGTTTCCACCCGAGGCAGA GCAAGACCACAAGATTCAGAGGGAGTAAGGAGTTCCGAATTGGAGAGGTT GAGGGGCGTGTGAGCCGTCAAGTGGGGCGCGTACGCAAAGAAAGAAGCGT CCATGTCAGAGGCCCAGCGGCCGTTGCGGCCCTACATGGGTGATCACGGT 5 GGGCCGTAGGCGGACCGGAGATGAGCGCGGCTCCGCCCACCGGACGGCGA GGGGCACGGCGCCTTCGTCCGGGGCGCTCGCGCGCGATCTCGCGCGCGCG GGGGGCGCCGGCGTCGCCGTCGTCGGCGACGGCCAGCCGCCCATCGTCCA CGCCCTCGGGCACGTCATCAACGCCGCGCTCCGCAGCCGGGCGGCCTGGA TGGTCGATCCTGTGCTGATCGACGCGGGCCCCTCCACGCAGAGCTTCTCC 0 GAGCTCGTCGGCGAGCTCGGGCGCGGCGCGGTCGACACCTTGATCCTCCT CGACGTGAACCCCGTGTACGCCGCGCCGGCCGACGTCGATTTCGCGGGCC TCCTCGCGCGCGTGCCCACGAGCTTGAAGGCCGGGCTCTACGACGACGAG ACCGCCCGCGCTTGCACGTGGTTCGTGCCGACCCGGCATTACCTCGAGTC GTGGGGGGACGCGCGGGCGTACGACGGGACGGTCTCGTTCGTGCAACCCC 5 TCGTCCGGCCGCTGTTCGACGGCCGGGCGGTGCCCGAGCTGCTCGCCGTC TTCGCGGGGGACGAGCGCCCGGATCCCCGGCTGCTGCTGCGCGAGCACTG GCGCGGCGAGCGCGGAGGGGCGGATTTCGAGGCCTTCTGGGGCGAGGCAT TGAAGCGCGGCTTCCTCCCTGACAGCGCCCGGCCGAGGCAGACACCGGAG CTCGCGCCGGCCGATCTCGCTCAGGAGCTCGCGCGGCTCGCCGCCGCGCC 0 GCGGCCGGCCGGCGGCGCGCTCGACGTGGCGTTCCTCAGGTCGCCGTCGC WO 00/22139 PCT/US99/23535 155 TCCACGACGGCAGGTTCGCCAACAACCCCTGGCTGCAAGAGCTCCCGCGG CCGATCACCAGGCTCACCTGGGGCAACGCCGCCATGATGAGCGCGGCGAC CGCGGCGCGGCTCGGCGTCGAGCGCGGCGATGTCGTCGAGCTCGCGCTGC GCGGCCGCACGATCGAGATCCCGGCCGTCGTCGTCCGCGGGCACGCCGAC GACGTGATCAGCGTCGACCTCGGCTATGGGCGCGACGCCGGCGAGGAGGT CGCGCGCGGGGTGGGCGTGTCGGCGTATCGGATCCGCCCGTCCGACGCGC GGTGGTTCGCGGGGGGCCTCTCCGTGAGGAAGACCGGCGCCACGGCCGCG CTCGCGCAGGCCCAGCTCGAGCTCTCCCAGCACGACCGTCCCATCGCGCT CAGGAGGACGCTGCCGCAGTACCGTGAACAGCCCGGTTTCGCGGAGGAGC ACAAGGGGCCGGTCCGCTCGATCCTGCCGGAGGTCCAGCACACCGGCGCG CAATGGGCGATGTCCATCGACATGTCGATCTGCACCGGGTGCTCCTCGTG CGTCGTGGCCTGTCAGGCCGAGAACAACGTCCTCGTCGTCGGCAAGGAGG AGGTGATGCACGGCCGCGAGATGCAGTGGTTGCGGATCGATCAGTACTTC GAGGGGGGAGGCGACGAGGTGAGCGTCGTCAACCAGCCGATGCTCTGCCA GCACTGCGAGAAGGCGCCGTGCGAGTACGTCTGTCCGGTGAACGCGACGG TCCACAGCCCCGACGGCCTCAACGAGATGATCTACAACCGATGCATCGGG ACGCGCTTTTGCTCCAACAACTGCCCGTACAAGATCCGGCGGTTCAATTT CTTCGACTACAATGCCCACGTCCCGTACAACGCCGGCCTCCGCAAGCTCC AGCGCAACCCGGACGTGACCGTCCGCGCCCGCGGCGTCATGGAGAAATGC ) ACGTACTGCGTGCAGCGGATCCGAGAGGCGGACATCCGCGCGCAGATCGA GCGGCGGCCGCTCCGGCCGGGCGAGGTGGTCACCGCCTGCCAGCAGGCCT GTCCGACCGGCGCGATCCAGTTCGGGTCGCTGGATCACGCGGATACCAAG ATGGTCGCGTGGCGCAGGGAGCCGCGCGCGTACGCCGTGCTCCACGACCT CGGCACCCGGCCGCGGACGGAGTACCTCGCCAAGATCGAGAACCCGAACC CCGAGATTGAATGAGCCATGGCGGGCCCGCTCATCCTGGACGCACCGACC GACGATCAGCTGTCGAAGCAGCTCCTCGAGCCGGTATGGAAGCCGCGCTC CCGGCTCGGCTGGATGCTCGCGTTCGGGCTCGCGCTCGGCGGCACGGGCC TGCTCTTCCTCGCGATCACCTACACCGTCCTCACCGGGATCGGCGTGTGG GGCAACAACATCCCGGTCGCCTGGGCCTTCGCGATCACCAACTTCGTCTG GTGGATCGGGATCGGCCACGCCGGGACGTTCATCTCCGCGATCCTCCTCC WO 00/22139 PCT/US99/23535 156 TGCTCGAGCAGAAGTGGCGGACGAG ZCATCAACCGCTTCGCCGAGGCGATG ACGCTCTTCGCGGTCGTCCAGGCCGGC -CTC TTTCCGGTCCTCCACCTCGG CCGCCCCTGGTTCGCCTACTGGAT7C7TCCCGTACCCCGCGACGATGCAGG TGTGGCCGCAGTTCCGGAGCGCGC7GCCGTGGGACGCCGCCGCGATCGCG 5 ACCTACTTCACGGTGTCGCTCCTGTT7CTCGTACATGGGCCTCGTCCCGGA TCTGGCGGCGCTGCGCGATCACGcC CCGGGCCGCGTCCGGCGGGTGATCT ACGGGCTCATGTCGTTCGGCTGGCAC GGCGCCGCCGACCACTTCCGGCAT TACCGGGTGCTGTACGGGCTGCTCG-CGGGGCTCGCGACGCCCCTCGTCGT CTCGGTGCACTCGATCGTGAGCAGCGATTTCGCGATCGCCCTGGTCCCCG 0 GCTGGCACTCGACGCTCTTTCCCCGTTCTTCGTCGCGGGCGCGATCTTC TCCGGGTTCGCGATGGTGCTCACC-GCTCATCCCGGTGCGGCGGATCTA CGGGCTCCATAACGTCGTGACCGC'-CGCCACCTCGACGATCTCGCGAAGA TGACGCTCGTGACCGGCTGGATCGT-CATCCTCTCGTACATCATCGAGAAC TTCCTCGCCTGGTACAGCGGCTCC-2CGTACGAAATGCATCAGTTTTTTCA 5 GACACGCCTGCGCGGCCCGAACAACG--CCGCCTACTGGGCCCAGCACGTCT GCAACGTGCTCGTCATCCAGCTCCT C-TGGAGCGAGCGGATCCGGACGAGC CCCGTCGCGCTCTGGCTCATCTCCATCCTCGTCAACGTCGGGATGTGGAG CGAGCGGTTCACGCTCATCGTGAT-2TCGCTCGAGGAAGAGTTCCTCCCGT CCAAGTGGCACGGCTACAGCCCGAC -3TGGGTGGACTGGAGCCTCTTCATC 0 GGGTCAGGCGGCTTCTTCATGCTCCTGTTCCTGAGCTTTTTGCGCGTCTT TCCGTTCATCCCCGTCGCGGAGGT G-AAGGAGCTCAACCATGAAGAGCTGG AGAAGGCTCGGGGCAAGGGGGGGC 3C-TGATGGAGACCGGAACGCTCGGCG AGTTCGACGACCCGGAGGCGATGC: -CCATGCGATCCGAGAGCTCAGGCGG CGCGGCTACCGCCGGGTGGAAGC TT CACGCCCTATCCGGTGAAGGGGCT 5 CGACGAGGCGCTCGACCTCCCGCC-CCAACCTCAACCGGATGGTGCTGC CCTTCGCGATCCTGGGGGTCGTGG'-CGGCTACTTCGTCCAGTGGTTCTGC AACGCTTTCCACTATCCGCTGAAC --- 7TGGGCGGGCGCCCGCTGAACTCGGC GCCGGCGTTCATCCCGATCACGT: CC3AGATGGGGGTGCTCTCCACCTCGA TCTTCGGCGTGCTCATCGGCTTTTAC--CTGACGAGGCTGCCGAGGCTCTAC 0 CTCCCGCTCTTCGACGCCCCGGGCTT CGAGCGCGTCACGCTGGATCGGGT WO 00/22139 PCTIUS99/23535 157 CCGTGGTGCAAGACCTCTTGGGCAGG AGCGCGATCTCCTCGCGCTCGGCGCCAGGCGCGTCGTCGTGGCGAGGAGG CGCGAGGAGCCATGAGGGCCGGCGCCCCGGCTCGCCCCCTCGGGCGCGCG CTCGCGCCGTTCGCCCTCGTCCTGCTCGCCGGGTGCCGCGAGAAGGTGCT 5 GCCCGAGCCGGACTTCGAGCGGATGATCCGCCAGGAGAAATACGGGCTCT GGGAGCCGTGCGAGCACTTCGACGACGGCCGCGCGATGCAGCACCCGCCC GAGGG-GACCGTCGCGCGCGGGCGCGTCACCGGGCCGCCCGGCTATCTCCA GGGCGTCCTCGACGGGGCGTACGTCACGGAGGTGCCGCTCTCGCTCACGG TCGAG 'CTCGTGCAGCGCGCCGGCAGCGCTTCGAGACCTTCTGCGCGCCG 0 TGCCACGGGATCCTCGGCGACGGCAGCTCGCGCGTGGCGACGAACATGAC GCTGCGCCCGCCGCCGTCGCTCGTCGGACCCGAGGCGCGGAGCTTCCCGC CGGGC-AGGATCTACCAGGTCATCATCGAGGGCTACGGCCTGATGCCGCGC TACT CGGACGATCTGCCCGACATCGAACAGCGCTGGGCCGTCCTCGCCTA CGTGAAGGCGCTTCAGCTGAGCCGCGGAGTGGCCGCGGGCGCCCTCCCGC 5 CCGCG-CTCCGCGGCCGGGCAGAGCAGGAGCTGCGATGAACAGGGATGCCA TCTAGTACAAGGGCGGCGCGACGATCGCGGCCTCGCTCGCGATCGCGGCG CTCGG 'CGCGGTCGCCGCGATCGTCGGCGGCTTCGTCGATCTCCGCCGGTT CTTCTTCTCGTACCTCGCCGCGTGGTCGTTCGCGGTATTCCTGTCCGTGG GCGCG-CTCGTCACGCTCCTCACCTGCAACGCCATGCGCGCGGGCTGGCCC 0 ACGCC-GGTGCGCCGCCTCC "TCGAGACGATGGTGGCGCCGCTGCCCCTGCT CGCGGCGCTCTCCGCGCCGATCCTGGTCGGCCTGGACACGCTGTACCCGT GGATG CACCCCGAGCGGATCGCCGGCGAGCACGCGCGGCGCATCCTCGAG CACAG-'AACGCCCTACTTCAATCCAGGCTTCTTCGTCGTGCGCTCGGCGAT CTACT-TCGCGATCTGGATCGCCGTCGCCCTCGTGCTCCGCCGGCGATCGT 5 TCGCGCAGGACCGTGAGCCGAGGCCCGACGTCAAGGACGCGATGTATGGC CTGACJCCGCGCCATGCTGCCGGTCGTGGCGATCACGATCGTCTTCTCGTC GTTCCACTGGCTCATGTCCCTCGACGCGACCTGGTACTCGACGATGTTCC CGGT-CTACGTGTTCGCGAGCGCCTC-GTGACCCCGTCGGCGCGCTCACG GTCCT'-CTCGTATGCCGCGCAGACGT.-CCGGTTACCTCGCGAGGCTCAACGA 0 CTCC-ACTATTACGCGCTCGGGCGGCTCCTCCTCGCGTTCACGATATTCT WO 00/22139 PCT/US99/23535 158 GGGCCTATGCGGCCTATTTCCAGTTCATGTTGATCTGGATCGCGAACAAG CCCGACGAGGTCGCCTTCTTCCTCGACCGCTGGGAAGGGCCCTGGCGGCC GACCTCCGTGCTCGTCGTCCTCACGCGGTTCGTCGTCCCGTTCCTGATCC TGATGTCGTACGCGATCAAGCGGCGCCCGCGCCAGCTCTCGTGGATGGCG 5 CTCTGGGTCGTCGCCTCCGGCTACATCGACTTTCACTGGCTCGTGGTGCC GGCGACAGGGCGCCACGGGTTCGCCTATCACTGGCTCGACCTCGCGACCC TGTGCGTCGTGGGCGGCCTCTCGACCGCGTTCGCCGCGTGGCGGCTGCGA GGGCGGCCGGTGGTCCCGGTCCACGACCCGCGGCTCGAAGAGGCCTTTGC GTACCGGAGCATATGATGTTCCGTTTCCGTCACAGCGAGGTTCGCCAGGA 0 GGAGGACACGCTCCCCTGGGGGCGCGTGATCCTCGCGTTCGCCGTCGTGC TCGCGATCGGCGGCGCGCTGACGCTCTGGGCCTGGCTCGCGATGCGGGCC CGCGAGGCGGATCTGCGGCCCTCCCTCGCGTTCCCGAGAAGGATCTCGG GCCGCGGCGCGAGGTCAGCATGGTCCAGCAGTCGCTGTTCGACGAGGCGC GCCTGGGCCAGCAGCTCGTCGAGGCGCAGCGCGCGGAGCTCCGCCGCTTC 5 GGCGTCGTCGATCGGGAGAGGGGCATCGTGAGCATCCCGATCGACGACGC GATCGAGCTCATGGTGGCGGAGGGCGCGCGATGAGCCGGGCCGTCGCCGT GGCCCTCCTGCTGGCAGCCGGCCTCGTGTCGCGCCCGGGCGCCGCGTCCG AGCCCGTATCGCTTTCGCCCCGCGCTGGGCCCGTCCGCGGGCGAGGCCGC GCTCTGAAACGACGGCTCCGGCGCGGATGAGCGGCCCGAGGCGACCTCCT 0 GCAACCCACCGCGCTGCGTACAGGGGTAAATCAACTGCATTCCAGGATAC GGACCGCGCAGCATAAACCCTCACCGGACAGACTGAATAATGCCGAACCT TGAACTTCTATGCCCATGCGTGCGGGATCATCATGCCCAACTATTTAAAC TGGTCCCTCCGGCAAAAGGAACGGACCAGCACCCAGAATAACCCCTGTTT GGCCAGCGCAAAAAAATGAAAACTCTTCTCCTTGCGGCTAAAATAAACGA 5 CTCCGGGGAACCGAATGGTATGCAATACACCATGGCAACGCGATTCGTCC TAACCTTAAACAAACTTCCCAGCGACTCGTCCGTCGAACGCTTCTGACGC AAGACCATGACCCCACGAGAACCGGGCGGCGGACACACTGCCAGTGAAAC TCGGCCTAGGCCCGCCCTGCCTTCACGTATTCACCGTGGGGCGGTCCAAA ACT-AAACAATACGTGACTCTTCTCAAATATCGTCGGATAAAGGCCAAC 0 ACGCGTACCTCCCCCTAAAGGGAAGAAACCCCTACCAGGGTGGACCGTAT WO 00/22139 PCT/US99/23535 159 CCACCCGTGATCCCTCAAACATCTC -CAGCCGCGTACAAATTAGGCTTTGA CAAAACC SEQ ID No 80 (>Contig55) GGGAGATGGGACGAGGGACATAACCA GCAGCAGAANGCAAAAAAGGAAAGGA AGAAAATGAAGGAA-GGGAAAGACCA CTGAGAAAGAACAC CATAAAGTCAGACTGGGGTAAAGCCATACACGCAGC GAACGCACAATATACGTCAAAACAAA AAGAGAAAGAGGAGGGCTGGATAGCG AGCCAACAATATACCTTTCACAGGG31-CGAGAGGGCCCAAGGTTCAATC GAAGACGATTGAATCCAAGGAAGTC CAATCGGAAGAAAAAACCATATTGA TAAACCAGACAACGACAGCAGGCCTG, AACGTAGGAGCGAGATCGTGAGAC ATCAGTAGGCkAAACAAGAGCGCTAC-AC CCAGGGGTCGTCAACCTAGAAA GGCGCGTCCTCAAGCCGGTAGCGGC-CGCGCGCGACCAGCCCGATGCGGGC GCCTTCGCGCGCGAACCGCCGCACCGTCGCGCGCCCCACGCCCGCTGACG CCCCCGTGATCACCACGACCTCCG"CCGCCTGGAATCGCCCATGCCCGTC GCCTCCCGCCTCGCCCGCGGCGTCAAGCAACGTGAATGCCACCTGAGCGT GTCACTTCCTCAAGCTCGACAGCAC -GTCCTTGATCCGCTCGGTCGGACCC GCCGTGAGCGACCAGGGGCTCGGCTG'-CCGCACGACGTGCAGGTCGCCTCG ACGCTCGAGCACCTCGAACCGCGTCG-'TTCCCTGCTCGGTCCGGACGAACC GGAGCGCCACCACGGCCGTGCCCACATGGAGGTTCGAGAGGGTGATCTCG GGCAGCCACGCCGGCAGCGCCGGGT.rCGACCAGCAGCAGGTCGAGCGGCC GAACGGGTACAGCCCGAGCATCGCCTGGAGCATCGCGAACACGCTCGAGC AGGACCAGGCCTGCGGCCAGTTGGCC -TTCGGGTACAGCGCGGGGAACGGG TGCTCCGCGTCGCGCGGGTGGCCGC-TCCAGCACTCGGGCAGCCGGTGGTG CTCGAACAGCGCCGCCGCCTCGAAC-ACGGCGCGGCACAGGAGCGCCACGT GCCCGTGCAGGCCGTACCCCGAGC -CCGAGCGCGATCGCGCCCTGATCG ACGGGCCAGACCGTCCCCCGGTGA7TAGCTGTACGGATCGAACGCGGGGTG ATCG.GCCGAGAGCGTGCGGATACr-CCAGCCGGAGAACATGTCCGCCGCGA WO 00/22139 PCT/US99/23535 160 ACATGCGGATGGCGGTGGGCTCGGCGAGGGCCTGGTCCACGATCCCCGCC GCGAGGCAGAGCCCCGGATCCGAGCCGATCGAGCGGATCTGGCGCTTGTC CGGGCCGAGGCCCATCGCGAAGGTGCGCGCGTCGGGCATCCAGAAGGCGT CGTTGAACCGCCTCTGCAGCTCGAGCGCCTCGGCGAACAGCCGTCGCGCG 5 TCGTCCTTGCGGCCGAACCAGAAGAGCAGCTCGGAGAGGCGCAGCTTCGA CAGGAACACGAAGCCCTGCATCTCGCACGTCCCGATCGGCGGCCGCACCT GAGAGCCGTCGGCGTGGACGATGGCGTCGTCGGAGTCCTTCCAGCCCTGG TTCTGGATCGACGCGCTCGAGCGGGGCTCGTACTCGTAGAACCCGTCGCC GTCGAGATCGCCCTCCTCGTCGATCCAGCGCATGGCCCTGAGCGCAGGCT 0 CGATCAGGCGGCCGACGCGCTCGCGATCGCCGGTCCAGTGCCAGAGCTCC GAGGCGGCCACCGCGTAGAACATCGTCGAGGTCGCCGACGCGTACGTGCG CCCCAGCGGGTTGTAGTTGAGGTCCGAGAGCGCTCCGTCCCTGGCCTGAT GCAGCATCCGGTCGGGCTGCTCGTCGCGCCAGTCGTCGACGACGCGCCCC TGCCAGCGCGGGAGCACGAGCGCTGTGCCTGCGAGGATGTCGGTCGTCAG CGCGGCGGCCTGCGTGCCCGCGGCGAGCGGGTCGCGGCCGAAGAGCCCGA TGTAGATCGGCAGTCCGGCGGCCACCGTCCAGGAGCGCTCGTCCTGGTCG ATATCGTACATGCGGAGCGCGATGAGATCGCGCTTGGCTCGCTCGAGCAC GGAGAAGACCGTATGCGAGAGCGTGTCGGCGCCCGGGACCGAGAAGGACG TGGCGCGGTGGTGGAAGGTGCCGCGCGCCACGTCGCGCGCGTTTCGCGTG D CCGAAGAACGAGCGGCAGCCGGCGAGCAGCGGGAGCGGTTCGCCGCGGAT CAGGGCGATCACGTCGACGCAGCCGCGCCAGGTGCCATGGGGCTCGAGAT CGATCGAGAACCGGATCTCGCGGCCAGCGCAGGACGGGGGCGAGCCCGCG CTCCGGGCCCGTACGACGATCCCGGCGTCGAAGCGCGCGACGCCGGATTC TCCGGGGTGTTCATAGCGGTGCTCGGCGCGGTAGTCGCAGCGCAGCGCGC D ATCCGTGCTCGGCGGGCTCGAGCGCCCACCGGGCGTCGCCGCGCTGGAGG CGCGGGCCGTCCGTCTCCTCCGCGTCGGCGAAGTCGGCGTCGATCTCGAG CGCCAGCGTGAAGCGCACGCGCTC CTGCGTGAAGCTCGCGACGTCGATGT CCTCGTGGAAGCCGTCCCCCACGAAGCGCGACAGCCGCAGCTCGACGGTC CGCGGCGCCGCGCCGCCGCCCTCGGGCGGCGGGGCGATGTAGTAGCCGAG D CCAGCTGTCCGGCTCGACGGCGGAGAGCGCGACGGGCGCCGGCGGCCTGC WO 00/22139 PCT/US99/23535 161 CGTCGATCAGGTGGCGGTAGAGGGAGAGGAGGCGGGTGTTGCGCACGAAC AGGCCGATGTGCGGCTCGGGGGCGATCGAGCCGTCCGGACGCATGCACAG GACCGTCCGGTTCTGGCTGATGTACAGGGAGCCGGCGCGGGGCCTCAGCG TGGCCAGCGAGCCGAAGGGTCTCTCGAGCGACATGGTCACCTCCAGGCGA 5 GCCCGGGGTGAGGACTGCCAGGGGCGTGCCAACGACGTGGACGCGCTCAC GCCAAGCCGCTGGGCGGGCGCGGCGGCCCCTGCGCCCGAGGCTCAGCCGA GCGCGAGCGGTGTTTCGTCGGCGCGAGCGGGCCTCGTCGTCGCCTCCAGG TAGGCCTTTCCGATGTCGGCCTCGTCCACGAACCCGACGATCGCGCCCTC GCCGTCGACGACGGGGACCTCGCGGACGCCGTGCGCCACCATCGCCTCGG 0 TCGCCGTCCGCAGATCGTCGGTGACCGTCACGGCCACCGGCGGCTGCATC GCGTCGGCGGCCACGGTCATCCGCTCGAGGTCGTGCTCCACCGCGATGAT CCGGAGCGACTCGGCGGTGATCATGCCGACCATCTTGCGCGACGGTTCGA GCACCGGGAACACCTCCTGCCAGCTCGCGTCGGCCGCCCGCCGGAGCATC TCGCGGGCCGGCGTCCCCGGCACGAACGTCACGAGCGCGCGCCCCTCGAT 5 CATGATCTGCCGCACGCGGATGGTCTTGAGCACGTCGAGCGTCGGCACCG GGTGCGCGGGAGACTCGCGCTGGGTGGGGAGCTGCGCGTGGTAGAGCGAG TGCTTCCGCAGCGCGACGAAGGCGACGCCCTCGGCGAGCATCAGCGGAAC CAGGAGGTCGTAGCTGCCGGCGAGCTCGCAGACCATCACGAGGGAGCTCA CCGGCACGTGCGCGACGCCGCCGTAGAAGGTGCCCATGCCCACGAGCGCG 0 AAGGCGCCCGGGTCGATGCGCGGATCGCCGAGCAGGAGCGCCGCCGCGCG CCCGAACGCGCCGCCGAAGAGCCCGCCGATGACGAGCGACGGCGCGAAGT CGCCGGCGCACCCGCCGCTGCCGAGCGTGAGCGACGAGGCGACGATCTTG GCGGCGCAGAGCAGGAGCAGGAGCTCCACGCCGCGCCAGCCCGGGTGGAG CCACGTGGCGCCGGTGATCGCGACCTGGACGGCGCCGTACCCGCCGCCGA 5 GCAGCCCGAGCCCTTGCCCGGGGCTCTCGATCCTGCGGCCGACGAACCAG AGGACGGGCACGCAGAAGAGGCCCAGCGCGAGCCCGCCGAGCCCCGGGCG CGC-CCAGGGGGCGATGGGCAGGCGCGCCGCGATCGCCTTCACGCCGCCGA GGCACTTCAGGAAGCCGATCGCGACGAAGGCCAGGAGCAGCGCGAGCAGC GCATAGAGAGGGAGGTGCGACGGGACGAACGCATACTTCGGCGCGTGCGC 0 GAAGAGCGTCGACTCGCCGTAGAACGAGATGAAGACCGAGTAGGAGACCA WO 00/22139 PCT/US99/23535 162 CGCTGGCGAGCAGCGCCGGGATCAGCGCCTCGGCCTCGAAGTCGTCGCGG TAGAGCACCTCGACGGCGAGCAGGGCGGCGCCGAGCGGCGTGCGGAAGAT GGCGGACATCCCGGCCGCGACCCCCGCGAGCATCAGGATGCGGTGCTCGC GCCGGCCGACCGCGAGCCCGCGCCCCACGAGCGAGCCGAGCGCTCCTCCG 5 ACCTGCATGGTCGGCCCCTCGCGACCGCCGGCGCCGCCCGAGCCGAGCGT GAGGATCGACGCGACCGCCTTGACCCACGCGACCCGCTTGCGCATCCGGC CGCCGTGGTGGTGGAAGGCCTGGATCATCGCGTCGCCGCCGCCGCCCGCG GCCTCGGGGGCGAGGCGCCAGGTGAGGATGCCCCCGGCCAGCGCTCCGAG CGCCGGGATCAGCAGCAGCAGCCAGAGCCGGACGCTCCGGTGCTCGGGGC 0 CGTCGCCGCTGAAGATGGCCTCGCCGTGGGCTCGAAGCCGCGCGTAGCCG GCGAGGCGGCCGAGGAGCAGCTCCTCGACGAGCTCGAGGGCGCCGAAGAA GAGCACCGCGACGAGGCCCGCGATGGCCCCGACGAGCACGGCATGCAGGA TCGTGCGCCCGACGAGCCTGAGATCGAGGGGCGCGACCTCCGAGAGGAGC GCGGAGAAGGGGCGCCGCCGTCGCACCACGCCGGCGCGCTCTGCTGGGAA 5 TGGTTCCGTCACGGCGATGGT SEQ ID No 81 (>Contig56) GGATCCGGCCGCGAGCGGCTGCGGTGCCGATGCGCTCGACGGTGACGGGC GGGGTGATCGCGGGTCCGGAGCTCGGTGCGAGCTACTGGGCGGACAACCT o TCGGCAGCCGGTGCGCTTCGCTGCGGCGGCGCAAGCGCTGCTGGAGGGTG GCCCCGCGCTGTTCATCGAGATGAGCCCGCACCCGATCCTGGTGCCGCCC CTGGACGAGATCCAGACGGCGGCCGAGCAAGGGGGCGCTGCGGTGGGCTC GCTGCGGCGAGGGCAGGACGAGCGCGCGACGCTGCTGGAGGCGCTGGGGA CGCTGTGGGCGTCCGGCTATCCGGTGAGCTGGGCTCGGCTGTTCCCCGCG 5 GGCGGCAGGCGGGTTCCGCTGCCGACCTATCCCTGGCAGCACGAGCGGTG CTGGATCGAGGTCGAGCCTGACGCCCGCCGCCTCGCCGCAGCCGACCCCA CCAAGGACTGGTTCTACCGAACGGACTGGCCCGAGGTGCCCCGCGCCGCC CCGAAATCGGAGACAGCTCATGGGAGCTGGCTGCTGTTGGCCGACAGGGG TGGGGTCGGTGAGGCGGTCGCTGCAGCGCTGTCGACGCGCGGACTTTCCT *0 GCACCGTGCTTCATGCGTCGGCTGACGCCTCCACCGTCGCCGAGCAGGTA WO 00/22139 PCT/US99/23535 163 TCCGAAGCTGCCAGTCGCCGAAACGACTGGCAGGGAGTCCTCTACCTGTG GGGCCTCGACGCCGTCGTCGATGCTGGGGCATCGGCCGACGAAGTCAGCG AGGCTACCCGCCGTGCCACCGCACCCGTCCTTGGGCTGGTTCGATTCCTG AGCGCTGCGCCCCATCCTCCTCGCTTCTGGGTGGTGACCCGCGGGGCATG 5 CACGGTGGGCGGCGAGCCAGAGGCCTCTCTTTGCCAAGCGGCGTTGTGGG GCCTCGCGCGCGTCGCGGCGCTGGAGCACCCCGCTGCCTGGGGTGGCCTC GTGGACCTGGATCCTCAGAAGAGCC CGACGGAGATCGAGCCCCTGGTGGC CGAGCTGCTTTCGCCGGACGCCGAGGATCAACTGGCGTTCCGCAGCGGTC GCAGGCACGCAGCACGCCTTGTAGCCGCCCCGCCGGAGGGCGACGTCGCA 0 CCGATATCGCTGTCCGCGGAGGGGAGCTACCTGGTGACGGGCGGGCTGGG TGGCCTTGGTCTGCTCGTGGCTCGGTGGCTGGTGGAGCGGGGAGCTCGAC ATCTGGTGCTCACCAGCCGGCACGGGCTGCCAGAGCGACAGGCGTCGGGC GGAGAGCAGCCGCCGGAGGCCCGCGCGCGCATCGCAGCGGTCGAGGGGCT GGAAGCGCAGGGCGCGCGGGTGACCGTGGCAGCGGTGGATGTCGCCGAGG 5 CCGATCCCATGACGGCGCTGCTGGCCGCCATCGAGCCCCCGTTGCGCGGG GTGGTGCACGCCGCCGGCGTCTTCC CCGTGCGTCACCTGGCGGAGACGGA CGAGGCCCTGCTGGAGTCGGTGCTC CGTCCCAAGGTGGCCGGGAGCTGGC TGCTGCACCGGCTGCTGCGCGACCGGCCTCTCGACCTGTTCGTGCTGTTC TCGTCGGGCGCGGCGGTGTGGGGTGGCAAAGGCCAAGGCGCATACGCCGC 0 GGCCAATGCGTTCCTCGACGGGCTCGCGCACCATCGCCGCGCGCACTCGC TGCCGGCGTTGAGCCTCGCCTGGGGCTTATGGGCCGAGGGAGGCATGGTT GATGCAAAGGCTCATGCACGTCTGAGCGACATCGGGGTCCTGCCCATGGC CACGGGGCCGGCCTTGTCGGCGCTGGAGCGCCTGGTGAACACCAGCGCTG TCCAGCGTTCGGTCACACGGATGGACTGGGCGCGCTTCGCGCCGGTCTAT 5 GCCGCGCGAGGGCGGCGCAACTTGCTTTCGGCTCTGGTCGCGGAGGACGA GCGCGCTGCGTCTCCCCCGGTGCCGACGGCAAACCGGATCTGGCGCGGCC TGTCCGTTGCGGAGAGCCGCTCAGCCCTCTACGAGCTCGTTCGCGGCATC GTCGCCCGGGTGCTGGGCTTCTCCGACCCGGGCGCGCTCGACGTCGGCCG AGGCTTCGCCGAGCAGGGGCTCGACTCCCTGATGGCTCTGGAGATCCGTA 0 ACCGCCTTCAGCGCGAGCTGGGCGAACGGCTGTCGGCGACTCTGGCCTTC WO 00/22139 PCTIUS99/23535 164 GACCACCCGACGGTGGAGCGGCTGG'-TGGCGCATCTCCTCACCGACGTGCT GAAGCTGGAGGACCGGAGCGACAC CCGGCACATCCGGTCGGTGGCGGCGG ATGACGACATCGCCATCGTCGGTGCCGCCTGCCGGTTCCCAGGTGGGGAT GAGGGCCTGGAGACATACTGGCGGCATCTGGCCGAGGGCATGGTGGTCAG 5 CACCGAGGTGCCAGCCGACCGGTGG-CGCGCGGCGGACTGGTACGACCCCG ATCCGGAGGTTCCGGGCCGGACCT ATGTGGCCAAGGGTGCCTTCCTCCGC GATGTGCGCAGCTTGGATGCGGCC-TTCTTCGCCATTTCCCCTCGTGAGGC GATGAGCCTGGACCCGCAACAGCGGC -TGTTGCTGGAGGTGAGCTGGGAGG CGATCGAGCGCGCTGGCCAGGACC CGATGGCGCTGCGCGAGAGCGCCACG o GGCGTGTTCGTGGGCATGATCGGC-A- GCGAGCACGCCGAGCGGGTGCAGGG CCTCGACGACGACGCGGCGTTGCT2'-TACGGCACCACCGGCAACCTGCTCA GCGTCGCCGCTGGACGGCTGTCGTT-CTTCCTGGGTCTGCACGGCCCGACG ATGACGGTGGACACCGCCTGCTCC-TCGTCGCTGGTGGCGTTGCACCTCGC CTGCCAGAGCCTGCGATTGGGCGAG3TGCGACCAGGCCCTGGCCGGCGGGT 5 CCAGCGTGCTTTTGTCGCCGCGGT-CATTCGTCGCGGCGTCGCGCATGCGT TTGCTTTCGCCAGATGGGCGGTGC-AAGACGTTCTCGGCCGCTGCAGACGG CTTTGCGCGGGCCGAGGGCTGCGC C-GTGGTGGTGCTCAAGCGGCTCCGTG ACGCGCAGCGCGACCGCGACCCCJt- CCTGGCGGTGGTCAGGAGCACGGCG ATCAACCACGATGGCCCGAGCAGC SGGCTCACGGTGCCCAGCGGTCCTGC o CCAGCAGGCGTTGCTACGCCAGGC-"-CTGGCGCAAGCGGGCGTGGCGCCGG CCGAGGTCGATTTCGTGGAGTGCC-AC -GGGACGGGGACAGCGCTGGGTGAC CCGATCGAGGTGCAGGCGCTGGGCG'-CGGTGTACGGGCGGGGCCGCCCCGC GGAGCGGCCGCTCTGGCTGGGCG-TGTCAAGGCCAACCTCGGCCACCTGG AGGCCGCGGCGGGCTTGGCCGGCC-TGCTCAAGGTGCTCTTGGCGCTGGAG 5 CACGAGCAGATTCCGGCTCAACCG32 AGCTCGACGAGCTCAACCCGCACAT CCCG-TGGGCAGAGCTGCCAGTGCCGTTGTCCGCAGGGCGGTCCCCTGGC CGCGJCGGCGCGCGCCCGCGTCGTG C-AGGCGTGAGCGCTTTCGc3CCTGAGC GGGACCAACGCGCATGTGGTGTT -Z3AGGAGGCGCCGGCGGTGGAGCCTGT GGCC\-GCGGCCCCCGAGCGCGCACGAGCTGTTCGTCCTGTCGGCGAAGA 0 GCGC GGCGC-CGCTGGATGCGCAC'-3CAGCCCGGCTGCGGGACCACCTGGAG WO 00/22139 PCT/US99/23535 165 AAGCATGTCGAGCTTGGCCTCGGCGATGTGGCGTTCAGCCTGGCGACGAC GCGCAGCGCGATGGAGCACCGGCTGGCGGTGGCCGCGAGCTCGCGCGAGG CGCTGCGAGGGGCGCTTTCGGCCGCAGCGCAGGGGCACACGCCGCCGGGA GCCGTGCGTGGGCGGGCCTCGGGCGGCAGCGCGCCGAAGGTGGTCTTCGT GTTTCCCGGCCAGGGCTCGCAGTGGGTGGGCATGGGCCGAAAGCTCATGG CCGAAGAGCCGGTCTTCCGGGCGGCGCTGGAGGGTTGCGACCGGGCCATC GAGGCGGAAGCGGGCTGGTCGCTGCTCGGGGAGCTCTCCGCCGACGAGGC CGCCTCGCAGCTCGGGCGCATCGACGTGGTTCAGCCGGTGCTGTTCGCCA TGGAAGTAGCGCTTTCTGCGCTGTGGCGGTCGTGGGGAGTGGAGCCGGAA D GCGGTGGTGGGCCACAGCATGGGCGAGGTTGCGGCGGCGCACGTGGCCGG CGCGCTGTCGCTCGAGGACGCGGTGGCGATCATCTGCCGGCGCAGCCGGC TGCTGCGGCGGATCAGCGGTCAGGGGGAGATGGCGCTGGTCGAGCTGTCG CTGGAGGAGGCCGAGGCGGCGCTGCGTGGCCATGAGGGTCGGCTGAGCGT GGCGGTGAGCAACAGCCCGCGCTCGACCGTGCTCGCCGGCGAGCCGGCGG CGCTCTCGGAGGTGCTGGCGGCGCTGACGGCCAAGGGGGTGTTCTGGCGG CAGGTGAAGGTGGACGTCGCCAGCCATAGCCCGCAGGTCGACCCGCTGCG CGAAGAGCTGATCGCGGCGCTGGGAGCGATCCGGCCGCGAGCGGCTGCGG TGCCGATGCGCTCGACGGTGACGGGCGGGGTGATCGCGGGTCCGGAGCTC GGTGCGAGCTACTGGGCGGACAACCTTCGGCAGCCGGTGCGCTTCGCTGC GGCGGCGCAAGCGCTGCTGGAGGGTGGCCCCGCGCTGTTCATCGAGATGA GCCCGCACCCGATCCTGGTGCCGCCCCTGGACGAGATCCAGACGGCGGCC GAGCAAGGGGGCGCTGCGGTGGGCTCGCTGCGGCGAGGGCAGGACGAGCG CGCGACGCTGCTGGAGGCGCTGGGGACGCTGTGGGCGTCCGGCTATCCGG TGAGCTGGGCTCGGCTGTTCCCCGCGGGCGGCAGGCGGGTTCCGCTGCCG * ACCTATCCCTGGCAGCACGAGCGGTACTGGATCGAGGACAGCGTGCATGG GTCGAAGCCCTCGCTGCGGCTTCGGCAGCTTCGCAACGGCGCCACGGACC ATCCGCTGCTCGGGGCTCCATTGCTCGTCTCGGCGCGACCCGGAGCTCAC TTGTGGGAGCAAGCGCTGAGCGACGAGAGGCTATCCTACCTTTCGGAACA TAGGGTCCATGGCGAAGCCGTGTTGCCCAGCGCGGCGTATGTAGAGATGG CGCTCGCCGCCGGCGTAGATCTCTATGGCACGGCGACGCTGGTGCTGGAG WO 00/22139 PCT/US99/23535 166 CAGCTGGCGCTCGAGCGAGCCCTCGCCGTGCCCTCCGAAGGCGGACGCAT CGTGCAAGTGGCCCTCAGCGAAGAAGGTCCCGGTCGGGCCTCATTCCAGG TATCGAGTCGTGAGGAGGCAGGTAGGAGCTGGGTGCGGCACGCCACGGGG CACGTGTGTAGCGGCCAGAGCTCAGCGGTGGGAGCGTTGAAGGAAGCTCC 5 GTGGGAGATTCAACGGCGATGTCCGAGCGTCCTGTCGTCGGAGGCGCTCT ATCCGCTGCTCAACGAGCACGCCCTCGACTATGGTCCCTGCTTCCAGGGC GTGGAGCAGGTGTGGCTCGGCACGGGGGAGGTGCTCGGCCGGGTACGCTT GCCAGGAGACATGGCATCCTCAAGTGGCGCCTACCGGATTCATCCCGCCT TGTTGGATGCATGTTTTCAGGTGCTGACAGCGCTGCTCACCACGCCGGAA 3 TCCATCGAGATTCGGAGGCGGCTGACGGATCTCCACGAACCGGATCTCCC GCGGTCCAGGGCTCCGGTGAATCAAGCGGTGAGTGACACCTGGCTGTGGG ACGCCGCGCTGGACGGTGGACGGCGCCAGAGCGCGAGCGTGCCCGTCGAC CTGGTGCTCGGCAGCTTCCATGCGAAGTGGGAGGTCATGGAGCGCCTCGC GCAGGCGTACATCATCGGCACTCTCCGCATATGGAACGTCTTCTGCGCTG 5 CTGGAGAGCGTCACACGATAGACGAGTTGCTCGTCAGGCTTCAAATCTCT GTCGTCTACAGGAAGGTCATCAAGCGATGGATGGAACACCTTGTCGCGAT CGGCATCCTTGTAGGGGACGGAGAGCATTTTGTGAGCTCTCAGCCGCTGC CGGAGCCTGATTTGGCGGCGGTGCTCGAGGAGGCCGGGAGGGTGTTCGCC GACCTCCCAGTCCTATTTGAGTGGTGCAAGTTTGCCGGGGAACGGCTCGC D GGACGTATTGACCGGTAAGACGCTCGCGCTCGAGATCCTCTTCCCTGGTG GCTCGTTCGATATGGCGGAGCGAATCTATCGAGATTCGCCCATCGCCCGT TACTCGAACGGCATCGTGCGCGGTGTCGTCGAGTCGGCGGCGCGGGTGGT AGCACCGTCGGGAATGTTCAGCATCTTGGAGATCGGAGCAGGGACGGGCG CGACCACCGCCGCCGTCCTCCCGGTGTTGCTGCCTGACCGGACGGAGTAC 5 CATTTCACCGATGTTTCTCCGCTCTTCCTTGCTCGCGCGGAGCAAAGATT TCGAGATTATCCATTCCTGAAGTATGGCATTCTGGATGTCGACCAGGAGC CAGCTGGCCAGGGATACGCACATCAGAGGTTTGACGTCATCGTCGCGGCC AATGTCATCCATGCGACCCGCGATATAAGAGCCACGGCGAAGCGTCTCCT GTCGTTGCTCGCGCCCGGAGGCCTTCTGGTGCTGGTCGAGGGCACAGGGC D ATCCGATCTGGTTCGATATCACCACGGGATTGATTGAGGGGTGGCAGAAG WO 00/22139 PCTIUS99/23535 167 TACGAAGATGATCTTCGTATCGACC/ -ATCCGCTCCTGCCTGCTCGGACCTG GTGTGACGTCCTGCGCCGGGTAGCGCTTTGCGGACGCCGTGAGTCTGCCAG GCGACGGATCTCCGGCGGGGATCC--CGGACAGCACGTGATCCTCTCGCGC GCGCCGGGCATAGCAGGAGCCGCT7GTGACAGCTCCGGTGAGTCGGCGAC DCGAATCGCCGGCCGCGCGTGCAGT-ACGGCAGGAATGGGCCGATGGCTCCG CTGACGTCGTCCATCGGATGGCGTrn:GGAGAGGATGTACTTCCACCGCCGG CCGGGCCGGCAGGTTTGGGTCCACGG- -TCGATTGCGTACCGGTGGAGGCGC GTTCACGAAGGCGCTCGCTGGAGA-7CTGCTCCTGTTCG\AGACACCGGGC AGGTCGTGGCAGAGGTTCAGGGGOCC- CGCCTGCCGCAGCTCGAGGCTTCT D CTCCCGGGCCCI7-ZAATGTTCCTGAT GCAGCGCAAAGACCCTATACCAGA---Q:CTCCGGCAGCCGCGTCTTCTTCCT CCGCGGGGGCTTGGCTCGTGCTGI-T-GGACCAGGGCGGGACAGGCGCTGCG CTCGTATCGCTGCTGGAAGGGCGAGG k-CGAGGCGTGCGTGCGCGTCATCGC GGGTACGGCATACGCCTGCCTCGCGC-CGGGGCTGTATCAAGTCGATCCGG DCGCACCCAGATGGCTTTCATACCC-:CTCCGCGATGCATTCGGCGAGGAC CGGATTTGTCGCGCGGTAGTGCATATGTGGAGCCTTGATGCGACGGCAGC AGGGGAGAGGGCGACAGCGGAGTC~CTTCAGGCCGATCAACTCCTGGGGA GCCTGAGCGCGCTTTCTCTGGTGCAGGCGCTGGTGCGCCGGAGGTGGCGC AACATGCCGCGGCTTTGGCTCTTGACCCGCGCCGTGCATGCGGTGGGCGC DGGAGGACGCAGCGGCCTCGGTGC-CAGGCGCCGGTGTGGGGCCTCGGTC GGACGCTCGCGCTCGAGCATCCA -7 CTGCGGTGCACGCTCGTGGACGTG AACCCGGCGCCGTCTCCAGAGGACGC2 -AGCCGCACTGGCGGTGGAGCTCGG GGCGAGCGACAGAGAGGACCAGGTC -GCATTGCGCTCGGATGGCCGCTACG TGGCGCGCCTCGTGCGGAGCTCC:T-TTCCGGCALAGCCTGCTACGGATTGC DGGCATCCGGGCGGACGGCAGCTATG TGATCACCGATGGCATGGGGAGAGT GGGGCTCTCGGTCGCGCAATGGATGGZ 'TGATGCAGGGGGCCCGCCATGTGG TGCTCGTGGATCGCGGCGGCGCTT CCGAGGCATCCCGGGATGCCCTCCGG TCCATGGCCGAGGCTGGCGCGGAC-CTGCAGATCGTGGAGGCCGACGTGGC TCGGCGCGACGATGTCGCTCGGC: C C-TCTCGAAGATCGAACCCTCGATGC DCGCCGCTTCGGGGGATCGTGTACCT*G1-GACGGGACCTTCCAGGGCGACTCC WO 00/22139 PCT/US99/23535 168 TCGATGCTGGAGCTGGATGCCCGTCGCTTCAI&GGAGTGGATGTATCCCAA GGTGCTCGGAGCGTGGAACCTGCACGCGCTGACCAGGGATAGATCGCTGG ACTTCTTCGTCCTGTATTCCTCGGGCACCTCGCTTCTGGGCTTGCCAGGA CAGGGGAGCCGCGCCGCCGGTGACGCCTTCTTGGACGCCATCGCGCATCA CCGGTGCAAGGTGGGCCTTACAGCGATGAGCATCAACTGGGGATTGCTCT CCGAAGCATCATCGCCGGCGACCCCGAACGACGGCGGAGCACGGCTCGAA TACCGGGGGATGGAAGGCCTCACGCTGGAGCAGGGAGCGGCGGCGCTCGG GCGCTTGCTCGCACGACCCAGGGCGCAGGTAGGGGTGATGCGGCTGAATC TGCGC CAGTGGTTGGAGTTXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX XXXXTATGGTATAACTTATTGATTATAATACAGTATACAGGTCCCTTT TCAGG:GACCCTTTCGTATGTTGTAG-CTGATTTTATTTTCTTCTTTTCTTT TGGGTTATGCTTTATTTAAAATAAGT CCCCATCTGTCTATCTATAGCGTCATGTTTTTCAGGATTTCTTAATTTCT GCAGCAGTTTAGATATATATTTCGCAGGTACTTTATTATTATGAATTA TGGGATTGATACATTTCCTTTGTCCAATCTAATCTTTTCCTGATTTCAA TACCTCACTCTCATCTCTATTAATTATAAAACCGAGCTTTCCATACGGAC CTGTTAAATATGATTGTAATTGTCTATACTCAGATGGACCTAATTCTTCA AAATTITTTAGCATCAAAAACAACTTGTCTTGTTTTATAGTCCTCCAATAC TCGTTTCCAAAAATCAGATTTGCCACCATTGGTGCCTATAATATCTCGTC TCTGAACTGCGTTACCATTTGGATG -GGACTTGATGTCTGTTAGGTGGGAT GCAAATACTATTCTTAGTGCGTCAAACACCATTGTTCATTCAGTGGC ACC7TCATTTCCTATCGGTATCTGATCTAGATGAGTAGTTATTTGACCTA TTG-TTTTATTTCTAATGGCTGAATTATCTGAAATAATATTAATATCATAT TCGTCATTTATCTCCTCTGCTTCCTCTGGAGCAAGTGCATTACGATTTAG ATTCAAACCAAGCCAGTAACATGGATGAATTAATAATTTCTCATTACTTT CAAAACCTTTATCTGGAGTTCGCC -CGTCATGGCAAAATGAATAGGATGAG GTGT--TTTATCACGAATAC CAACAAATCCTACACTATACAAACTTTGGAG AATTC -CACTTGCCTTTAACAACTG TATTTCAGACGTTATTTTAGGATCTC CAT7TTCTTCGATTAATTCGAAAGATGCTTCTATTTTTTTTAAGCACGTA TAACTGTTA&TTCAGGTTCAAT'3CTACGAAATGCACTAGTTATAACCTG WO 00/22139 PCT/US99/23535 169 TATTGAAGGAAAGATCTTCTGATACTCTTTCCAGAGATCTTCAAGTCTGG CCATGGAAATTGACTTGGCTGCATATTCTAGGTCAGTGTTTATGATAGTT TCTCTATTCTCTCTGAATGCGGAAAAAAAAGCTTCATTCAACAATGATAG TAAATCCCTGGGCCGGTAAAGGGTAAATTGCAAACATCGCTTAAAACCAT TCCTCCCTTTAAGATCATCCGCTGTGCATCTATCCCAAACTCGTTGATCT TTCTCAATATCTAGCTTAAATGCTACTTTCATTCTTTTAGCTGACAGCAT TAGGAGTTGTGCCCAGTCCCAATGCAACCTTATGACTTGACCCTCTATAT TTCTCGAGTAATCAGGATCTTCCTTTGATAGCGACCTAAATATATTATCC CTTAAAAAAATTATTGGACGAATGCATTTTGCTTTTTGATTTAATTCAAT ) AGATGCATATGCTAGACCTGCAATGATTCCAATTCCTATATTATCCGGTT CATACGCCTCATCTAGCTTATCCATTAATATGACAACTTTCCTGTCTGAG CGTTCAAGAAGTGATACTATATTATTTTCTATTTCTGAGATATTCAAATT GAATTGAAGATCACCAATTGATTCTTCTGGGTTATTTTCATCTAAATACT CCTTTGCGACAAGCCTACACTTTCTTAAAATGTCACCTTGTGCAGAATTC 5 CATTTTTTCAAATGTTCATTCAACAATGTTTCTGATGATATTTGAGATGA CAATTTGTAATGAGATGATATATATGATGCTATCTCCATTAGCATAGCGT ATCGCCATAATAGTCTTGTTGCTGCCCTTGCTAAATTAAATGATCCTGTA AATGGTTTCAACATTGATCTGAAACCAATAATTTGAGAATCGTCTGGTGA GAAACTCAGGATTAATATTTTTTTGTCTTTCTTCCAATGCTCATTTAGCT D GAATAAATAAAGCACTTTTACCTGTCCCTCGTCTACCAACAACAATGGTC CTGTCATCAGTTTCAATTAGAGTCCTAAAGTCAGCAGTTTCAATGAAAGC ATTACTCAACATCTTTTTATCATTTTCTGCTGTCGTATCACCAAACGGAT TAGACTTTGAAGTAATATTCAATTCCATATTCAACCTTTTATGTTAGTTG CTTTCATTTATTACTTTATATACTGTTGAACGAGCAATATTCATTGTTTT 5 TGATATATGTGAGGCACCTAACCCCTGTTGCCACATATTTAATACTGCAT CTCTATCTATTTTTCTTTTTCTACCAAAAACAACTCCTTTTGCCA SEQ ID No 82 (>Contig57) TCATCTATTGTATAGTTTGTATATTGATATGATATAATTATAACATATAA 0 ACAGTAAACTTTCTCTACGTAGATCGAGGAGAAGACTCAATTTGTTGACA WO 00/22139 PCT/US99/23535 170 TCXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXACTACTCGCATACCGTTG CGCAACAGCGGCGCGAGGAGCAGGACGCATACGACATCACCGGCAATACG CTCAGCGTCGCCGACGGACGGTTGTCTTATACGCTAGGGCTGCAGGGACC CTGCCTGACCGTCGACACGGTCTGCTCGTCGTCGCTCGTGGCCATCCACC 5 TTGCCTGCCGCAGCCTGCGCGCTCGCGAGAGCGATCTCGCGCTGGCGGGA GGCGTCAACATGCTCCTTTCGTCCAAGACGATGATAATGCTGGGGCGCAT CCAGGCGCTGTCGCCCGATGGCCACTGCCGGACATTCGACGCCTCGGCCA ACGGGTTCGTCCGTGGGGAGGGCTGCGGTATGGTCGTGCTCAAACGGCTC TCCGACGCCCAGCGACACGGCGATCGGATCTGGGCTCTGATCCGGGGTTC 0 GGCCATGAATCAGGATGGCCGGTCGACAGGGTTGATGGCACCCAATGTGC TCGCTCAGGAGGCGCTCTTGCGCGAGGCGCTGCAGAGCGCTCGCGTCGAC GCCGGGGCCATCGGTTATGTCGAGACCCACGGAACGGGGACCTCGCTCGG CGACCCGATCGAGGTCGAGGCGCTGCGTGCCGTGTTGGGGCCGGCGCGGG CCGATGGGAGCCGCTGCGTGCTGGGCGCAGTGAAGACAAACCTCGGCCAC 5 CTGGAGGGCGCTGCAGGCGTGGCGGGTTTGATCAAGGCGGCGCTGGCTCT GCACCACGAACTGATCCCGCGAAACCTCCATTTCCACACGCTCAATCCGC GGATCCGGATCGAGGGGACCGCGCTCGCGCTGGCGACGGAGCCGGTGCCG TGGCCGCGGGCGGGCCGACCGCGCTTCGCGGGGGTGAGCGCGTTCGGCCT CAGCGGCACCAACGTCCATGTCGTGCTGGAGGAGGCGCCGGCCACGGTGC 0 TCGCACCGGCGACGCCGGGGCGCTCAGCGGAGCTTTTGGTGCTGTCGGCG AAGAGCGCCGCCGCGCTGGACGCACAGGCGGCGCGGCTCTCAGCGCACAT CGCCGCGTACCCGGAGCAGGGTCTCGGAGACGTCGCGTTCAGCCTGGTAT CGACGCGTAGCCCGATGGAGCACCGGCTCGCGGTGGCGGCGACCTCGCGC GAGGCCCTGCGAAGCGCGCTGGAGGTTGCGGCGCAGGGGCAGACCCCGGC 5 AGGCGCGGCGCGCGGCAGGGCCGCTTCCTCGCCCGGCAAGCTCGCCTTCC TGTTCGCCGGGCAGGGCGCGCAGGTGCCGGGCATGGGCCGTGGGTTGTGG GAGGCGTGGCCGGCGTTCCGCGAGACCTTCGACCGGTGCGTCACGCTCTT CGACCGGGAGCTCCATCAGCCGCTCTGCGAGGTGATGTGGGCCGAGCCGG GCAGCAGCAGGTCGTCGTTGCTGGACCAGACGGCGTTCACCCAGCCGGCG 0 CTCTTTGCGCTGGAGTACGCGCTGGCCGCGCTCTTCCGGTCGTGGGGCGT WO 00/22139 PCT/US99/23535 171 GGAGCCGGAGCTCGTCGCTGGCCA AGCCTCGGCGAGCTGGTGGCCGCCT GCGTGGCGGGTGTGTTCTCCCTCGAGGACGCCGTGCGCTT GGTGGTCGCG CGCGGCCGGTTGATGCAGGCGCTGC-CGGCCGGCGGCGCGATGGTATCGAT CGCCGCGCCGGAGGCCGACGTGGCT-GCCGCGGTGGCGCCGCACGCAGCGT TGGTGTCGATCGCGGCAGTCAATG-GG-CCGGAGCAGGTGGTGATCGCGGGC GCCGAGAAATTCGTGCAGCAGATC GC GGCGGCGTTCGCGGCGCGGGGGGC GCGAACCAAACCGCTGCATGTCTC-GCACGCGTTCCACTCGCCGCTCATGG ATCCGATGCTGGAGGCGTTCCGGCGG- -GTGACTGAGTCGGTGACGTACCGG CGGCCTTCGATCGCGCTGGTGAGCACCTGAGCGGGAJAGCCCTGCACCGA TGAGGTGAGCGCGCCGGGTTACTG3GTGCGTCACGCGCGAGAGGCGGTGC GCTTCGCGGACGGAGTGAAGGCGC---GCACGCGGCCGGTGCGGGCCTCTTC GTCGAGGTGGGGCCGAAGCCGACGC-TGCTCGGCCTTGTGCCGGCCTGCCT GCCGGATGCCAGGCCGGTGCTGCT CCCAGCGTCGCGCGCCGGGCGTGACG AGGCTGCGAGCGCGCTAGAGGCGC-TGGGTGGGTTCTGGGTCGTCGGTGGA TCGGTCACCTGGTCGGGTGTCTTCQECTTCGGGCGGACGGCGGGTACCGCT GCCAACCTATCCCTGGCAGCGCGAGCGTTACTGGATCGA.JGCGCCGGTCG ATCGTGAGGCGGACGGCACCGGC CG--TGCTCGGGCGGGGGGCCACCCCCTT CTGGGTGAAGTCTTTTCCGTGTCGACCCATGCCGGTCTGCGCCTGTGGGA GACGACGCTGGACCGAAAGCGGCTG,-CCGTGGCTCGGCGAGCACCGGGCGC AGGGGGAGGTCGTGTTTCCTGGCG CCGGGTACCTGGAGATGGCGCTGTCG TCGGGGGCCGAGATCTTGGGCGA7GGACCGATCCAGGTCACGGATGTGGT GCTCATCGAGACGCTGACCTTCGCGGGCGATACGGCGGTACCGGTCCAGG TGGTGACGACCGAGGAGCGACCGGG-,-'ACGGCTGCGGTTCCAGGTAGCGAGT CGGGAGCCGGGGGAACGTCGCGCG-C CCTTCCGGATCCACGCCCGCGGCGT GCTGCGCCGGATCGGGCGCGTCA-ACCCCGGCGAGGTCGAA~CCTCGCCG CCCTGCGCGCCCGGCTTCATGCCG"CCGTGCCCGCTGCGGCTATCTATGGT GCGC -TCGCCGAGATGGGGCTTCAATLACGGCCCGGCGTTGCGGGGGCTCGC CGAGCTGTGG CGGGGTGAGGGCGAG--GCGCTGGGCAGGGTGAGACTGCCTG AGGCCGCCGGCTCCGCGACAGCC?-ACCAGCTGCATCCGGTGCTGCTGGAC GCGTGCGTCCAAATGATTGTTGGC*SCGTTCGCCGATCGCGATGAGGCGAC WO 00/22139 PCT/US99/23535 172 GCCGTGGGCGCCGGTGGAGGTGGGCTCGGTGCGGCTGTTCCAGCGGTCTC CTGGGGAGCTATGGTGCCATGCGCGCGTCGTGAGCGATGGTCAACAGGCC TCCAGCCGGTGGAGCGCCGACTTTGAGTTGATGGACGGTACGGGCGCGGT GGTCGCCGAGATCTCCCGGCTGGTGGTGGAGCGGCTTGCGAGCGGTGTAC 5 GCCGGCGCGACGCAGACGACTGGTTCCTGGAGCTGGATTGGGAGCCCGCG GCGCTCGGTGGGCCCAAGATCACAGCCGGCCGGTGGCTGCTGCTCGGCGA GGGTGGTGGGCTCGGGCGCTCGTTGTGCTCGGCGCTGAAGGCCGCCGGCC ATGTCGTCGTCCACGCCGCGGGGGACGACACGAGCACTGCAGGAATGCGC GCGCTCCTGGCCAACGCGTTCGACGGCCAGGCCCCGACGGCCGTGGTGCA 0 CCTCAGCAGCCTCGACGGGGGCGGCCAGCTCGGCCCGGGGCTCGGGGCGC AGGGCGCGCTCGACGCGCCCCGGAGCCCAGATGTCGATGCCGATGCCCTC GAATCGGCGCTGATGCGTGGTTGCGACAGCGTGCTCTCCCTGGTGCAAGC GCTGGTCGGCATGGACCTCCGAAACGCGCCGCGGCTGTGGCTCTTGACCC GCGGGGCTCAGGCGGCCGCCGCCGGCGATGTCTCCGTGGTGCAAGCGCCG 5 CTGTTGGGGCTGGGCCGCACCATCGCCTTGGAGCACGCCGAGCTGCGCTG TATCAGCGTCGACCTCGATCCAGCCGAGCCTGAAGGGGGAAGCCGATGCTT TGCTGGCCGAGCTACTTGCAGATGATGCCGAGGAGGAGGTCGCGCTGCGC GGTGGCGACCGGCTCGTTGCGCGGCTCGTCCACCGGCTGCCCGACGCTCA GCGCCGGGAGAAGGTCGAGCCCGCCGGTGACAGGCCGTTCCGGCTAGAGA 0 TCGATGAACCCGGCGCGCTGGACCAACTGGTGCTCCGAGCCACGGGGCGG CGCGCTCCTGGTCCGGGCGAGGTCGAGATCTCCGTCGAAGCGGCGGGGCT CGACTCCATCGACATCCAGCTGGCGTTGGGCGTTGCTCCCAATGATCTGC CTGGAGAAGAAATCGAGCCGTTGGTGCTCGGAAGCGAGTGCGCCGGGCGC ATCGTCGCTGTGGGCGAGGGCGTGAACGGCCTTGTGGTGGGCCAGCCGGT 5 GATCGCCCTTGCGGCGGGAGTATTTGCTACCCATGTCACCACGTCGGCCA CGCTGGTGTTGCCTCGGCCTCTGGGGCTCTCGGCGACCGAGGCGGCCGCG ATGC CCCTCGCGTATTTGACGGCCTGGTACGCCCTCGACAAGGTCGCCCA CCTGCAGGCGGGGGAGCGGGTGCTGATCCATGCGGAGGCCGGTGGTGTCG GTCTTTGCGCGGTGCGATGGGCGCAGCGCGTGGGCGCCGAGGTGTATGCG 0 ACCGCCGACACGCCCGAGAACCGTGCCTACCTGGAGTCGCTGGGCGTGCG WO 00/22139 PCT/US99/23535 173 GTACGTGAGCGATTCCCGCTCGGGCCGGTTCGTCACAGACGTGCATGCAT GGACGGACGGCGAGGGTGTGGACGTCGTGCTCGACTCGCTTTCGGGCGAG CGCATCGACAAGAGCCTCATGGTCCTGCGCGCCTGTGGTCGCCTTGTGAA GCTGGGCAGGCGCGACGACTGCGCCGACACGCAGCCTGGGCTGCCGCCGC 5 TCCTACGGAATTTTTCCTTCTCGCAGGTGGACTTGCGGGGAATGATGCTC GATCAACCGGCGAGGATCCGTGCGCTCCTCGACGAGCTGTTCGGGTTGGT CGCAGCCGGTGCCATCAGCCCACTGGGGTCGGGGTTGCGCGTTGGCGGAT CCCTCACGCCACCGCCGGTCGAGACCTTCCCGATCTCTCGCGCAGCCGAG GCATTCCGGAGGATGGCGCAAGGACAGCATCTCGGGAAGCTCGTGCTCAC 0 GCTGGACGACCCGGAGGTGCGGATCCGCGCTCCGGCCGAATCCAGCGTCG CCGTCCGCGCGGACGGCACCTACCTTGTGACCGGCGGTCTGGGTGGCCTC GGTCTGCGCGTGGCCGGATGGCTGGCCGAGCGGGGCGCGGGGCAACTGGT GCTGGTGGGCCGCTCCGGTGCGGCGAGCGCAGAGCAGCGAGCCGCCGTGG CGGCGCTGGAGGCCCACGGCGCGCGCGTCACGGTGGCGAAAGCGGACGTC 5 GCCGATCGGTCACAGATCGAGCGGGTCCTCCGCGAGGTTACCGCGTCGGG GATGCCGCTGCGGGGTGTCGTGCATGCGGCAGGTCTCGTGGATGACGGGC TGCTGATGCAGCAGACTCCGGCGCGGTTCCGCACGGTGATGGGACCTAAG GTCCAGGGGGCCTTGCACTTGCACACGCTGACACGCGAAGCGCCTCTTTC CTTCTTCGTGCTGTACGCTTCTGCAGCTGGGCTTTTCGGCTCGCCAGGCC 0 AGGGCAACTATGCCGCAGCCAACGCGTTCCTCGACGCCCTTTCGCATCAC CGAAGGGCGCAGGGCCTGCCGGCGCTGAGCATCGACTGGGGCATGTTCAC GGAGGTGGGGATGGCCGTTGCGCAAGAAAACCGTGGCGCGCGGCAGATCT CTCGCGGGATGCGGGGCATCACCCCCGATGAGGGTCTGTCAGCTCTGGCG CGCTTGCTCGAGGGTGATCGCGTGCAGACGGGGGTGATACCGATCACTCC 5 GCGGCAGTGGGTGGAGTTCTACCCGGCAACAGCGGCCTCACGGAGGTTGT CGCGGCTGGTGACCACGCAGCGCGCGGTCGCTGATCGGACCGCCGGGGAT CGGGACCTGCTCGAACAGCTTGCGTCGGCTGAGCCGAGCGCGCGGGCGGG GCTGCTGCAGGACGTCGTGCGCGTGCAGGTCTCGCATGTGCTGCGTCTCC CTGAAGACAAGATCGAGGTGGATGCCCCGCTCTCGAGCATGGGCATGGAC 0 TCGCTGATGAGCCTGGAGCTGCGCAACCGCATCGAGGCTGCGCTGGGCGT WO 00/22139 PCT/US99/23535 174 CGCCGCGCCTGCAGCCTTGGGGTGGACGTACCCAACGGTAGCAGCGATAA CGCGCTGGCTGCTCGACGACGCC CT CGTCGTCCGGCTTGGCGGCGGGTCG GACACGGACGAATCGACGGCGAGCGCCGGTTCGTTCGTCCACGTCCTCCG CTTTCGTCCTGTCGTCAAGCCGCGGGCTCGTCTCTTCTGTTTTCACGGTT 5 CTGGCGGCTCGCCCGAGGGCTTCCGTTCCTGGTCGGAGAAGTCTGAGTGG AGCGATCTGGAAATCGTGGCCATGTGGCACGATCGCAGCCTCGCCTCCGA GGACGCGCCTGGTAAGAAGTACGTCCAAGAGGCGGCCTCGCTGATTCAGC ACTATGCAGACGCACCGTTTGCGTTAGTAGGGTTCAGCCTGGGTGTCCGG TTCGTCATGGGGACAGCCGTGGAGCTCGCCAGTCGTTCCGGCGCACCGGC D TCCGCTGGCCGTCTTCACGTTGGGCGGCAGCTTGATCTCTTCTTCAGAGA TCACCCCGGAGATGGAGACCGATATAATAGCCAAGCTCTTCTTCCGAAAT GCCGCGGGTTTCGTGCGATCCACC CAACAAGTCCAGGCCGATGCTCGCGC AGACAAGGTCATCACAGACACCATGGTGGCTCCGGCCCCCGGGGACTCGA AGGAGCCGCCCGTGAAGATCGCGGTCCCTATCGTCGCCATCGCCGGCTCG 5 GACGATGTGATCGTGCCTCCGAGCGACGTTCAGGATCTACAATCTCGCAC CACGGAGCGCTTCTATATGCATCTCCTTCCCGGAGATCACGAATTTCTCG TCGATCGAGGGCGCGAGATCATGCACATCGTCGACTCGCATCTCAATCCG CTGCTCGCCGCGAGGACGACGTCGTCAGGCCCCGCGTTCGAGGCAAAATG ATGGCAGCCTCCCTCGGGCGCGCGAGATGGTTGGGAGCAGCGTGGGCGCT 0 GGCGGCCGGCGGCAGGCCGCGGAGGCGCATGAGCCTTCCTGGACGTTTGC AGTATAGGAGATTTTATGACACAGGAGCAAGCGAATCAGAGTGAGACGAA GCCTGCTTTCGACTTCAAGCCGTTCGCGCCTGGGTACGCGGAGGACCCGT TCCCCGCGATCGAGCGCCTGAGAGAGGCAACCCCCATCTTCTACTGGGAT GAAGGCCGCTCCTGGGTCCTCACCCGATACCACGACGTGTCGGCGGTGTT 5 CCGCGACGAACGCTTCGCGGTCAGTCGAGAAGAGTGGGAATCGAGCGCGG AGTACTCGTCGGCCATTCCCGAGCTCAGCGATATGAAGAAGTACGGATTG TTCGGGCTGCCGCCGGAGGATCACGCTCGGGTCCGCAAGCTCGTCAACCC GTCGTTTACGTCACGCGCCATCGACCTGCTGCGCGCCGAAATACAGCGCA CCGTCGACCAGCTGCTCGATGCTCGCTCCGGACAAGAGGAGTTCGACGTT 0 GTGCGGGATTACGCGGAGGGAATCCCGATGCGCGCGATCAGCGCTCTGTT WO 00/22139 PCT/US99/23535 175 GAAGGTTCCGGCCGAGTGTGACGAGAAGTTCCGTCGCTTCGGCTCGGCGA CTGCGCCCGCGCTCGGCGTGGG-TTGGTGCCCCAGGTCGATGAGGAGACC AAGACCCTGGTCGCGTCCGTCACCGAGGGGCTCGCGCTGCTCCATGACGT CCTCGATGAGCGGCGCAGGAACCCGC- -TCGAAAATGACGTCTTGACGATGC 5TGCTTCAGGCCGAGGCCGACGGCAG CAGGCTGAGCACGAAGGAGCTGGTC GCGCTCGTGGGTGCGATTATCGCTGC'7'-TGGCACCGATACCACGATCTACCT TATCGCGTTCGCTGTGCTCAACCTGC\ TGCGGTCGCCCGAGGCGCTCGAGC TGGTGAAGGCCGAGCCCGGGCTCATG,"AGGAJkCGCGCTCGATGAGGTGCTC CGCTTCGACAATATCCTCAGAATAGGAI&CTGTGCGTTTCGCCAGGCAGGA 0 CCTGGAGTACTGCGGGGCATCGATCAAkGAAAGGGGAGATGGTCTTTCTCC TGATCCCGAGCGCCCTGAGAGATGG-GACTGTATTCTCCAGGCCAGACGTG TTTGATGTGCGACGGGACACGGGC3--CGAGCCTCGCGTACGGTAGAGGCCC CCATGTCTGCCCCGGGGTGTCCCT-TGCTCGCCTCGAGGCGGAGATCGCCG TGGGCACCATCTTCCGTAGGTTCC C'CGAGATGAAGCTGAAAGAALACTCCC 5 GTGTTTGGATACCACCCCGCGTTCC-GGACATCGAATCACTCAACGTCAT CTTGAAGCCCTCCAAAGCTGGATAGC' -TCGCGGGGGTATCGCTTCCCGAJAC CTCATTCCCTCATGATACAGCTCGC GCGCGGGTGCTGTCTGCCGCGGGTG CGATTCGATCCAGCGGACAAGCCCATTGTCAGCGCGCGAJAGATCGATCC ACGGCCCGGAGAAGAGCCCGTCCGC-GTGACGTCGGAAGAAGTGCCGGGCG 0 CCGCC CTGGGAGCGCAAAGCTCGC-TCGTTCGCGCTCAGCACGCCGCTCGT CATGTCCGGCCCTGCACCCGCGCCG-:AGGAGCCGCCCGCCCTGATGCACGG CCTCACCGAGCGGCAGGTTCTGCTC-TCGCTCGTCGCCCTCGCGCTCGTCC TCCTGACCGCGCGCGCCTTCGGCGAGCTCGCGCGGCGGCTGCGCCAGCCC GAGGTGCTCGGCGAGCTCTTCGGCGGCGTGGTGCTGGGCCCGTCCGTCGT 5CGGCGCGCTCGCTCCTGGGTTCCAT-CGAGTCCTCTTCCAGGATCCGGCGG TCGGGGTCGTGCTCTCCGGCATCrC-CTGGATAGGCGCGCTCGTCCTGCTG CTCATGGCGGGTATCGAGGTCGATCSTGAGCATCCTGCGCAAGGAGGCGCG CCCGkOGGGCGCTCTCGGCGCTCGGC- -GCGATCGCGCCCCCGCTGCGCACGC CGG\GG7'"CCGCTGGTGCAGCGCATGC AGGGCGCGTTCACGTGGGATCTCGAC 0 GTCTC7GCCG CGACGCTCTGCGCAA-GCCTGAGCCTCGGCGCCTGCTCGTAC WO 00/22139 PCT/US99/23535 176 ACCTCGCCGGTGCTCGCTCCGCCCGCGGACATCCGGCCGCCCGCCGCGGC CCAGCTCGAGCCGGACTCGCCGGATGACGAGGCCGACGAGGCCGACGAGG CGCTCCGCCCGTTCCGCGACGCGATCGCCGCGTACTCGGAGGCCGTTCGG TGGGCGGAGGCGGCGCAGCGGCCGCGGCTGGAGAGCCTCGTGCGGCTCGC 5 GATCGTGCGGCTGGGCAAGGCGCTCGACAAGGTCCCTTTCGCGCACACGA CGGCCGGCGTCTCCCAGATCGCCGGCAGACTCCAGAACGATGCGGTCTGG TTCGATGTCGCCGCCCGGTACGCGAGCTTCCGCGCGGCGACGGAGCACGC GCTCCGCGACGCGGCGTCGGCCATGGAGGCGCTCGCGGCCGGCCCGTACC GCGGATCGAGCCGCGTGTCCGCTGCCGTAGGGGAGTTTCGGGGGGAGGCG 0 GCGCGCCTTCACCCCGCGGACCGTGTACCCGCGTCCGACCAGCAGATCCT GACCGCGCTGCGCGCAGCCGAGCGGGCGCTCATCGCGCTCTACACTGCGT TCGCCCGTGAGGAGTGAGCCTCTCTCGGGCGCAGCCGAGCGGCGGCGTGC CGGTGGTTCCCTCTTCGCAACCATGACCGGAGCCGCGCTCGGTCCGCGCA GCGGCTAGCGCGCGTCGCGGCAGAGATCGCTGGAGCGACAGGCGACGACC 5 CGCCCGAGGGTGTCGAACGGATTGCCGCAGCCCTCATTGCGGATCCCCTC CAGACACTCGTTCAGCTGCTTGGCGTCGATGCCGCCTGGGCACTCGCCGA AGGTCAGCTCGTCGCGCCACTCGGATCGGATCTTGTTCGAGCACGCGTCC TTGCTCGAATACTCCCGGTCTTGTCCGATGTTGTTGCACCGCGCCTCGCG GTCGCACCGCGCCGCCACGATGCTATCGACGGCGCTGCCGACTGGCACCG 0 GCGCCTCGCCCTGCGCGCCACCCGGGGTTTGCGCCTCCCCGCCTGACCGC TTTTCGCCGCCGCACGCCGCGAGCAGGCTCATTCCCGACACCGAGATCAG GCCCACGACCAGCTTCCCAGCAATCTTTTGCATGGCTTCCCCTCCCTCAC GACACGTCACATCAGAGACTCTCCGCTCGGCTCGTCGGTTCGACAGCCGG CGACGGCCACGAGCAGAACCGTCCCCGACCAGAACAGCCGCATGCGGGTT 5 TCTCGCAACATGCCCCGACATCCTTGCGACTAGCGTGCCTCCGCTCGTGC CGAGATCGGCTGTCCTGTGCGACGGCAATATCCTGCGATCGGCCGGGCAG GAGGTACCGACACGGGCGCCGGGCGGGAGGTGCCGCCACGGGCTCGAAAT GTGCTGCGGCAGGCGCCTCCATGCCCGCAGCCGGGAACGCGGCGCCCGGC CAGCCTCGGGGTGACGCCGCAAACGGGAGATGCTCCCGGAGAGGCGCCGG 0 GCACAGCCGAGCGCCGTCACCACCGTGCGCACTCGTGAGCTCCAGCTCCT WO 00/22139 PCT/US99/23535 177 CGGCATAGAAGAGACCGTCACTCCCGGTCCGTGTAGGCGATCGTGCTGAT CAGCGCGTTCTCCGCCTGACGCGAGTCGAGCCGGGTATGCTGCACGACAA TGGGAACGTCCGATTCGATCACGCTGGCATAGTCCGTATCGCGCGGGATC GGCTCGGGTTCGGTCAGATCGTTGAACCGGACGTGCCGGGTGCGCCTCGC D TGGGACGGTCACCCGGTACGGCCCGGCGGGGTCGCGGTCGCTGAAGTAGA CGGTGATGGCGACCTGCGCGTCCCGGTCCGACGCATTCAACAGGCAGGCC GTCTCATGGCTCGTCATCTGCGGCTCGGGTCCGTTGCTCCGGCCTGGGAT GTAGCCCTCTGCGATTGCCCAGCGCGTCCGCCCGATCGGCTTCTCCATAT GTCCTCCCTGCTGGCTCCTCTTTGGCTGCCTCCCTCTGCTGTCCAGGAGC D GACGGCCTCTTCTCCCGACGCGCTCGGGGATCCATGGCTGAGGATCCTCG CCGAGCGCTCCTTGCCGACCGGCGCGCCGAGCGCCGACGGGCTTTGAAAG CACGCGACCGGACACGTGATGCCGGCGCGACGAGGCCGCCCCGCGTCTGA TCCCGATCGTGACATCGCGACGTCCGCCGGCGCCTCTGCAGGCCGGCCTG AGCGTTGCGCGGTCATGGTCGTCCTCGCGTCACCGCCACCCGCCGATTCA D CATCCCACCGCGGCACGACGCTTGCTCAAACCGCGGCGAGACGGCCGGGC GGCTGTGGTACCGGCCAGCCCGGACGCGAGGCCCGAGAGGGACAGTGGGT CCGCCGTGAAGCAGTGAGGCGATCGAGGTGGCAGATGAAACACGTTGACA CGGGCCGACGAGTCGGCCGCCGGATAGGGCTCACGCTCGGTCTCCTCGCG AGCATGGCGCTCGCCGGCTGTGGCGGCCCGAGCGAGAAAATCGTGCAGGG D CACGCGGCTCGCGCCCGGCGCCGATGCGCACGTCGCCGCCGACGTCGACC CCGACGCCGCGACCACGCGGCTGGCGGTGGACGTCGTTCACCTCTCGCCG CCCGAGCGCATCGAGGCCGGCAGCGAGCGGTTCGTCGTCTGGCAGCGTCC GAGCTCCGAGTCCCCGTGGCAACGGGTCGGAGTGCTCGACTACAACGCTG CCAGCCGAAGAGGCAAGCTGGCCGAGACGACCGTGCCGCATGCCAACTTC D GAGCTGCTCATCACCGTCGAGAAGCAGAGCAGCCCTCAGTCTCCATCTTC TGCCGCCGTCATCGGGCCGACGTCCGTCGGGTAACATCGCGCTATCAGCA GCGCTGAGCCCGCCAGCAGGCCCCAGAGCCCTGCCTCGATCGCCTTCTCC ATCATATCATCCCTGCGTACTCCTCCAGCGACGGCCGCGTCGAAGCAACC GCCGTGCCGGCGCGGCTCTACGTGCGCGACAGGAGAGCGTCCTGGCGCGG D CCTGCGCATCGCTGGAAGGATCGGCGGAGCATGGAGAAAGAATCGAGGAT WO 00/22139 PCT/US99/23535 178 CGCGATCTACGGCGCCATCGCAGCCAACGTGGCGATCGCGGCGGTCAAGT TCATCGCCGCCGCCGTGACCGGCAGC--TCGGCGATGCTCTCCGAGGGCGTG CACTCCCTCGTCGATACTGCAGACG 'GCTCCTCCTCCTGCTCGGCAAJGCA CCGGAGCGCACGCCCGCCCGACGCCr-GAGCATCCGTTCGGCCACGGCAAGG 5AGCTCTATTTCTGGACGCTGATCGT7CGCCATCATGATCTTCGCCGCGGGC GGCGGCGTCTCGATCTACGAAGGGATCTTGCACCTCTTGCACCCGCGCCA GATCGAGGATCCGACGTGGAACTACG'TCGTCCTCGGCGCAGCGGCCGTCT TCGAGGGGACGTCGCTCATCATCT rCG'ATC CACGAGTTCAAGAAGAAGGAC GGACAGGGCTACCTCGCGGCGATGC GGTCCAGCAAGGACCCGACGACGTT DCACGATCGTCCTGGAGGACTCCGCGG: -CGCTCGCCGGGCTCACCATCGCCT TCTGCTTGTGGAC: -CGGACCTCTGCG GCGGCGTCGATCGGCATCGGCCT-CTGCTCGCCGCGGTCGCGGTCTTCCT CGCCAGCCAGAGCCGTGGGCTCCTC-GTGGGGGAGAGCGCGGACAGGGAGC TCCTCGCCGCGATCCGCGCGCTCGCC AGCGCAGATCCTGGCGTGTCGGCG DGTGGGGCGGCCCCTGACGATGCACT-TCGGTCCGCACGAAGTCCTGGTCGT GCTGCGCATCGAGTTCGACGCCGCGC-TCACGGCGTCCGGGGTCGCGGAGG CGAGGGAGCGCATCGAGACCCGGATACGGAGCGAGCGACCCGACGTGAAG CACATCTACGTCGAGGCCAGGTCGC -TCCACCAGCGCGCGAGGGCGTGACG CGCCGTGGAGAGACCGCGCGCGGCC-7TCCGCCATCCTCCGCGGCGCCCGGG DCTCAGGTGGCCCTCGCAGCAGGG -CGCCTGGCGGGCAAACCGTGCAGAC GTCGTCCTTCGACGCGAGGTACGC TG--GTTGCAJAGTCGTCACGCCGTATCG CGAGGTCCGGCAGCGCCGGAGCCCG GGCGGGCCGGGCGCACGAAGGCGCG GCGAGCGCAGGCTTCGAGGGGGGCG-:ACGTCATGAGGAAGGCCAGGGCGCA TGGGGCGATGCTCGGCGGGCGAGl-.mGACGGCTGGCGTCGCGGCCTCCCCG DGCGCCGGCGCGCTTCGCGCCGCGC-'-CCAGCGCGGTCGCTCGCGCGATCTC GCCCGGCGCCGGCTCATCGCCTCCGTGTCCCTCGCCGGCGGCGCCAGCAT GGCGGTCGTCTCGCTGTTCCAGC--CG,-GGATCATCGAGCGCCTGCCCGATC CTCCGCTTCCAGGTTCGATTC-3 C CAAGGTGACGAGCTCCGATATCGCG TTCGGGCTCACGATGCCGGACGCC CCGCTCGCGCTCACCAGCTTCGCGTC DCAACCTCGCGCTGGCTGGCTGGGGA -'\GGCGCCGAGCGCGCCAGGAACACCC WO 00/22139 PCTIUS99/23535 179 CCTGGATCCCCGTCGCCGTGGCGGCCAAGGCGGCCGTCGAGGCGGCCGTG TCCGGATGGCTCCTCGTCCAGATGCGACGGCGGGAGAGGGCCTGGTGCGC GTACTGCCTGGTCGCCATGGCGGCCAACATGGCCGTGTTCGCGCTCTCGC TCCCGGAAGGGTGGGCGGCGCTGGGGAAGGCGCGAGCGCGCTCGTGACAG 5 GACGGGCGCGGGCAGCCCCGGCCATCGGAGGCCGGCGTGCACCCGCTCCG TCACGCCCCAGCCCGCGCCGCGTGATCTCCCGCGGACAGGGCGCGTACCG TGGACCCCGCACGCGCCGCGTCGACGGACATCCCCGGCGACCCGCGCGGC GCGACCCGCGCAACTCCGGCCCGCCGCCGGGCATCGACATCTCCCGTGAG CAAGGGCACTCCGCTCCTGCCCGCGTCCGCGAACGATGGCTGCGCTGTTT 0 CCACCCTGGAGCAACTCCGTTTACCGCGTGGCGCTCGTCGGGCTCGTCGC CTCGGCGGGCGGCGCCATCCTCGCGCTCATGATCTACGTCCGCACGCCGT GGAAGCGATACCAGTTCGAGCCCGTCGATCAGCCGGTGCAGTTCGATCAC CGCCATCACGTGCAGGACGACGCCATCGATTGCGTCTACTGCCACACCAC GGTGACCCGCTCGCCCACGGCGGGGATGCCGCCGACGGCCACGTGCATGG 5 GGTGCCACAGCCAGATCTGGAATCAGAGCGTCATGCTCGAGCCCGTGCGG CGGAGCTGGTTCTCCGGCCACGCCGATCCCGTGGAACCGGGTGAAACTCC GTGCCCGACTTCGTCTATTTCAACCACGCGATCCACGTGAACAAGGGCGT GGGCTGGCGTGAAGCTGCCACGGGCGCGTGGACGAGATGGCGGCCGTCTA CAAGGTGGCGCCGATGACGATGGGCTGGTGCCTGGAGTGCCATCGCCTGC 0 CGGAGCCGCACCTCCGCCCGCTCTCCGCGATCACCGACATGCGCTGGGAC CCGGGGGAGCGGAGGGATGAGCTCGGGGCGCAGCTCGCGAAGGAATACGG GGTCCGGCGGCTCACGCACTGCACAGCGTGCCATCGATGAACGATGAACA GGGGATCTCCTTGAAAGACGCAGATGAGATGAAGGAA TGGTGGCTAGAAG CGCTCGGGCCGGCGGGAGAGCGCGCGTCCTACAGGCTGCTGGCGCCGCTC 5 ATCGAGAGCCCGGAGCTCCGCGCGCTCGCCGCGGGCGAACCGCCCCGGGG CGTGGACGAGCCGGCGGGCGTCAGCCGCCGCGCGCTGCTCAAGCTGCTCG GCGC-GAGCATGGCGCTCGCCGGCGTCGCGGGCTGCACCCCGCATGAGCCC GAGAAGATCCTGCCGTACAACGAGACCCCGCCCGGCGTCGTGCCGGGTCT CTCCCAATCCTACGCGACGAGCATGGTGCTCGACGGGTATGCCATGGGCC 0 TCCTCGCCAAGAGCTACGCGGGGCGGCCCATCAAGATCGAGGGCAACCCC WO 00/22139 PCT/US99/23535 180 GCGCACCCGGCGAGCCTCGGCGCGACCGGCGTCCACGAGCAGGCCTCGAT CCTCTCGCTGTACGACCCGTACCGCGCGCGCGCGCCGACGCGCGGCGGCC AGGTCGCGTCGTGGGAGGCGCTCTCCGCGCGCTTCGGCGGCGACCGCGAG GACGGCGGCGCTGGCCTCCGCTTCGTCCTCCAGCCCACGAGCTCGCCCCT 5 CATCGCCGCGCTGATCGAGCGCGTCCGGCGCAGGTTCCCCGGCGCGCGGT TCACCTTCTGGTCGCCGGTCCACGCCGAGCACGCGCTCGAAGGCGCGCGG GCGGCGCTCGGCCTCAGGCTCTTGCCTCAGCTCGACGTCGACCAGGCCGA GGTGATCCTCTCGCTGGACGCGGACTTCCTCGCGGACATGCCGTTCAGCG TGCGCTATGCGCGCGACTTCGCCGCGCGCCGCCGCCCCGCGAGCCCGGCG 0 GCGGCCATGAGCCGCCTCTACGTCGCGGAGGCGATGTTCACGCCCACGGG GACGCTCGCCGACCACCGGCTCCGCGTGCGGCCCGCCGAGGTCGCGCGCG TCGCGGCCGGCGTCGCGGTGGGAACTCGTGCACGAGTCTTTGTCTTGCGC CCTGTCCGGGAATAACGGACACCTTATCGCGGGTCGCTCTTTGTGCGCGG CTTCTGTACCTCTCAGGACAGGTAGAAGAGGGACTCAGGGGCCCTTATGT 5 TAACTGGGGATGCCTTCGGGACGGCCGCAAATATATCCTATCACCTCACT GGGTGTGGGGGAGCACCGCGAGGATGTACAACCTCTGTAACTCTATGTGA GATAATGTGTGCAGTGATCTGAGACTTATTTGTGTGACCGAGACGTCTCT CTTATTGGTACGCATAGTATAATATAACACGTCTCATACATACTCCCGAC ATATCCGCGGTATGCGCGCACATAGAATAGGTGATGATAAATCCCTAGTG 0 TGTGGAACTAGAAGATGCGGGAGTTACCTGATATTTACGGAAAAAGTATT ATCTCAACTACCTCTCTGTTGAGACTATCACTTCGGTGTCGTTGTGCTGC TGGT, or its complementary strand, 5 (b) DNA-sequences which hybridise under stringent conditions to regions of DNA-sequences according to (a) encoding proteins or to fragments of said DNA-sequences, WO 00/22139 PCTIUS99/23535 181 (c) DNA-sequences which hybridise to the DNA-sequences accord ing to (a) and (b) because of a degeneration of the genetic code, 5 (d) allele variations and mutants resulting by substitution, insertion or deletion of nucleotides or inversion of nucleotide segments of DNA-sequences according to (a) to (c) , wherein the variations and mutants offer isofunctional expression products. 0

11. Peptide encoded by a DNA sequence according to claim 10 selected from the group consisting of Seq ID No 83 >Contig56_003 2890 amino acids MW=307428 D pI=5.76 numambig=13 5 IRPRAAAVPMRSTVTGGVIAGPELGASYWADNLRQPVRFAAAAQALLEGGPALFIEMSPH PILVPPLDEIQTAAEQGGAAVGSLRRGQDEPATLLEALGTLWASGYPVSWARLFPAGGRR VPLPTYPWQHERCWIEVEPDARRLAAADPTKDWFYRTDWPEVPRAAPKSETAHGSWLLLA DRGGVGEAVAAALSTRGLSCTVLHASADASTVAEQVSEAASRRNDWQGVLYLWGLDAVVD AGASADEVSEATRRATAPVLGLVRFLSAAPHPPRFWVVTRGACTVGGEPEASLCQAALWG 0 LARVAALEHPAAWGGLVDLDPQKSPTEIEPLVAELLSPDAEDQLAFRSGRRHAARLVAAP PEGDVAPISLSAEGSYLVTGGLGGLGLLVARWLVERGARHLVLTSRHGLPERQASGGEQP PEARARIAAVEGLEAQGARVTVAAVDVAEADPMTALLAAIEPPLRGVVHAAGVFPVRHLA ETDEALLESVLRPKVAGSWLLHRLLRDRPLDLFVLFSSGAAVWGGKGQGAYAAANAFLDG LAHHRRAHSLPALSLAWGLWAEGGMVDAKAHARLSDIGVLPMATGPALSALERLVNTSAV 5 QRSVTRMDWARFAPVYAARGRRNLLSALVAEDERAASPPVPTANRIWRGLSVAESRSALY ELVRGIVARVLGFSDPGALDVGRGFAEQGLDSLMALEIRNRLQRELGERLSATLAFDHPT VERLVAHLLTDVLKLEDRSDTRHIRSVAADDDIAIVGAACRFPGGDEGLETYWRHLAEGM VVSTEVPADRWRAADWYDPDPEVPGRTYVAKGAFLRDVRSLDAAFFAISPREAMSLDPQQ RLLLEVSWEAIERAGQDPMALRESATGVFVGMIGSEHAERVQGLDDDAALLYGTTGNLLS 0 VAAGRLSFFLGLHGPTMTVDTACSSSLVALHLACQSLRLGECDQALAGGSSVLLSPRSFV WO 00/22139 PCT/US99/23535 182 AASRMRLLSPDGRCKTFSAAADGFAPAEGCAVVVLKRLRDAQRDRDPT LAVVRSTAINHD GPSSGLTVPSGPAQQALLRQALAQAGVAPAEVDFVECHGTGTALGDPIEVQALGAVYGRG RPAERPLWLCAVKANLCHLEAAAGLAGVLKVLLALEHEQI PAQPELDELNPHI PWAELPV AVVRRAVPWPRGARPRPAGVSAPGL SGTNAHVVLEEAPAVE PVAAAPEPAAELFVLSAKS 5 AALDAQAARLRDHLEKHiVELGLGDVAFSLATTRSAMEHRLAVAAS SREALRGALSAAAQ GHPGVGAGSPVFFGGSWGGKMEPFALGDAEAEA GWSLLGELSADEAASQLGRIDVVQVLFAMVEVALSALWRSWGVE PEAVVGHSMGEVAAAH VAGALSLEDAVAT TCRRSRLLRR- S3- QGEMALVELSLEEAEAALRGHEGRLSVAVSNSPR STVLAGEPAALSEVLAALTAKGVFWRQVKVDVASHSPQVDPLREELIALGARPAAV 0 PMRSTVTGGVIAGPELGASYWADNL-RQPVRFAAAAQALLEGGPALFIEMSPHPILVPPLD E IQTAAEQGGAAVGSLRRGQDEPATLLEALGTLWASGYPVSWARLFPAGGRRVRLPTYPW QHERYWT EDSVHGSKPSLRLRQLRNGATDHPLLGAPLLVSARPGAHLWEQALSDERLSYL S EHRVHGEAVLP SAAYVEMALAAGVDLYGTATLVLEQLALEPALAVPSEGGRI VQVALSE EGPGRASFQVSSREEAGRSWVRHATGHVCSGQSSAVGALKEAPWEIQRRCPSVLSSEALY 5PLLNEHALDYGPCFQGVEQVWLG-TGEVLGRVRLPGDMAS SSGAYRIHPALLDACFQVLTA LLTTPES IEIRRRLTDLHEPDLPRSRAPVNQAVSDTWLWDAALDGGRRQSASVPVDLVLG SPHAKWEVMERLAQAYT TGTLRIWTNVPCAAGERHTIDELLVRLQISVVYRKVTKRWMEHL VAT GILVGDGEHPVS SQPLPEPDLAAVLEEAGRVF'ADLPVLPEWCKFAGERLADVLTGKT LALEILFPGGSFDMAERIYRDSPIARYSNGIVRGVVESAARVVAPSGMFS TLEIGAGTGA 0 TTAAVLPVLLPDRTEYHFTDVSRLF7LARAEQRFRDYPFLKYGILDVDQEPAGQGYAHQRF DVIVAANVIHATRDIRATAKRLLSLLAPGGLLVLVEGTGHPIWFDITTGLIEGWQKYEDD LRIDHPLLPARTWCDVLRRVGFADAVSLPGDGSPAGILGQHVLSJARGIAGAJkCDSSGE SATES PAARAVRQEWADGSADVVHRMALERMYHRRPGRQVWVHGRLRTGGGAFTKQZLAG DLLLFEDTGQVVAEVQGLRLPQLEASAFAPRDPREEWLYALEWQRKDPI PEAPAAASSSS 5AGAWLVLMDQGGTGAALVSLLEGRG-EACVRVIAGTAYACLAPGLYQVDPAQPDGFHTLLR DAFGEDRI CRAVVHMWSLDATAAGE7PATAESLQADQLLGSLSALSLVQALVRRRWRNMPR LWLLTPAVHAVGAEDAAASVAQAPVWGLGRTLALEHPELRCTLVDVNPAP S EDAAALAV ELGASDREDQVALRSDGRYVARLVRSSFsGKPATDCGIRADGSYVT TDGMGRVGLSVAQW MVNQGARHVVLVDRGGASEASRDALRSMAEAGAEVQIVEADVARRDDVARLLSKI EPSMP 0 PLRGIVYVDG -TFQGDSSMLELDAR.-,RF'KEWMYPKVLGAWNLHALTRDRSLDFFvLYSSGTS WO 00/22139 PCT/US99/23535 183 LLGLPGQGSRAAGDAFLDAIAHHRCKVGLTAMSINWGLLSEASSPATPNDGGARLEYRGM EGLTLEQGAAALGRLLARPPAQVGVMRLNLRQWLEXXXXXXXXXXXXXWYNLLIIIQYTK VPFQGPFRML* 5 Seq ID No 84 >Contig56_027 700 amino acids MW=80569 D pI=7.02 numambig=0 MNMELNITSKSNPFGDTTAENDKKMLSNAFIETADFRTLIETDDRTIVVGRRGTGKSALF IQLNEHWKKDKKILILSFSPDDSQIIGFRSMLKPFTGSFNLARAATRLLWRYAMLMEIAS YISSHYKLSSQISSETLLNEHLKKWNSAQGDILRKCRLVAKEYLDENNPEESIGDLQFNL 0 NISEIENNIVSLLERSDRKVVILMDKLDEAYEPDNIGIGIIAGLAYASIELNQKAKCIRP IIFLRDNIFRSLSKEDPDYSRNIEGQVIRLHWDWAQLLMLSAKRMKVAFKLDIEKDQRVW DRCTADDLKGRNGFKRCLQFTLYRPRDLLSLLNEAFFSAFRENRETIINTDLEYAAKSIS MARLEDLWKEYQKIFPSIQVITSAFRSIEPELTVYTCLKKIEASFELIEENGDPKITSEI QLLKASGILQSLYSVGFVGIRDKNTSSYSFCHDGRTPDKGFESNEKLLIHPCYWLGLNLN 5 RNALAPEEAEEINDEYDINIISDNSAIRNKTIGQITTHLDQIPIGNEGATEFEQWCLDAL RIVFASHLTDIKSHPNGNAVQRRDIIGTNGGKSDFWKRVLEDYKTRQVVFDAKNFEELGP SEYRQLQSYLTGPYGKLGFIINRDESEVLKSGKDLDWTKEMYQSHNSLIIKLPAKYISKL LQKLRNPEKHDAIDRQMGKLLTLYETSYMAIKSTQKKRRK* 0 Seq ID No 85 >Contig57_001 372 amino acids MW=38411 D pI=12.39 numambig=10 MLTSXXXXXXXXXXLLAYRCATAARGAGRIRHHRQYAQRRRRTVVLYARAAGTLPDRRHG LLVVARGHPPCLPQPARSRERSRAGGRRQHAPFVQDDDNAGAHPGAVARWPLPDIRRLGQ RVRPWGGLRYGRAQTALRRPATRRSDLGSDPGFGHESGWPVDRVDGTQCARSGGALARGA 5 AERSRRRRGHRLCRDPRNGDLARRPDRGRGAACRVGAGAGRWEPLAGRSEDKPRPPGGR CRRGGFDQGGAGSAPRTDPAKPPFPHAQSADPDRGDRARAGDGAGAVAAGGPTALRGGER VRPQRHQRPCRAGGGAGHGARTGDAGALSGAFGAVGEERRRAGRTGGAALSAHRRVPGAG SRRRRVQPGIDA* WO 00/22139 PCT/US99/23535 184 Seq ID No 86 >Contig57_002 2259 amino acids MW=238258 D pI=5.92 numambig=0 MSYTLGLQGPCLTVDTVCSSSLVAIHLACRSLARESDLALAGGVNMLLSSKTMIMLGRI QALSPDGHCRTFDASANGFVRGEGCGMVVLKRLSDAQRHGDRIWALIRGSAMNQDGRSTG 5 LMAPNVLAQEALLREALQSARVDAGAIGYVETHGTGTSLGDPIEVEALRAVLGPARADGS RCVLGAVKTNLGHLEGAAGVAGLIKAALALHHELIPRNLHFHTLNPRIRIEGTALALATE PVPWPRAGRPRFAGVSAFGLSGTNVHVVLEEAPATVLAPATPGRSAELLVLSAKSAAALD AQAARLSAHIAAYPEQGLGDVAFSLVSTRSPMEHRLAVAATSREALRSALEVAAQGQTPA GAARGRAASSPGKLAFLFAGQGAQVPGMGRGLWEAWPAFRETFDRCVTLFDRELHQPLCE 0 VMWAEPGSSRSSLLDQTAFTQPALFALEYALAALFRSWGVEPELVAGHSLGELVAACVAG VFSLEDAVRLVVARGRLMQALPAGGAMVSIAAPEADVAAAVAPHAALVSIAAVNGPEQVV IAGAEKFVQQIAAAFAARGARTKPLHVSHAFHSPLMDPMLEAFRRVTESVTYRRPSIALV SNLSGKPCTDEVSAPGYWVRHAREAVRFADGVKALHAAGAGLFVEVGPKPTLLGLVPACL PDARPVLLPASRAGRDEAASALEALGGFWVVGGSVTWSGVFPSGGRRVPLPTYPWQRERY 5 WIEAPVDREADGTGPAPAGGHPLLGEVFSVSTHAGLRLWETTLDRKRLPWLGEHRAQGEV VFPGAGYLEMALSSGAEILGDGPIQVTDVVLIETLTFAGDTAVPVQVVTTEERPGRLRFQ VASREPGERRAPFRIHARGVLRRIGRVETPARSNLAALRARLHAAVPAAAIYGALAEMGL QYGPALRGLAELWRGEGEALGRVRLPEAAGSATAYQLHPVLLDACVQMIVGAFADRDEAT PWAPVEVGSVRLFQRSPGELWCHARVVSDGQQASSRWSADFELMDGTGAVVAEISRLVVE 0 RLASGVRRRDADDWFLELDWEPAALGGPKITAGRWLLLGEGGGLGRSLCSALKAAGHVVV HAAGDDTSTAGMRALLANAFDGQAPTAVVHLSSLDGGGQLGPGLGAQGALDAPRSPDVDA DALESALMRGCDSVLSLVQALVGMDLRNAPRLWLLTRGAQAAAAGDVSVVQAPLLGLGRT IALEHAELRCISVDLDPAEPEGEADALLAELLADDAEEEVALRGGDRLVARLVHRLPDAQ RREKVEPAGDRPFRLEIDEPGALDQLVLRATGRRAPGPGEVEISVEAAGLDSIDIQLALG 5 VAPNDLPGEEIEPLVLGSECAGRIVAVGEGVNGLVVGQPVIALAAGVFATHVTTSATLVL PRPLGLSATEAAAMPLAYLTAWYALDKVAHLQAGERVLIHAEAGGVGLCAVRWAQRVGAE VYATADTPENRAYLESLGVRYVSDSRSGRFVTDVHAWTDGEGVDVVLDSLSGERIDKSLM VLRACGRLVKLGRRDDCADTQPGLPPLLRNFSFSQVDLRGMMLDQPARIPALLDELFGLV AAGAISPLGSGLRVGGSLTPPPVETFPISRAAEAFRRMAQGQHLGKLVLTLDDPEVRIRA 0 PAESSVAVRADGTYLVTGGLGGLGLRVAGWLAERGAGQLVLVGRSGAASAEQPAAVAALE WO 00/22139 PCT/US99/23535 185 AHGARVTVAKADVADRSQIERVLREVTASGMPLRGVVHAAGLVDDGLLMQQTPARFRTVM GPKVQGALHLHTLTREAPLSFFVLYASAAGLFGSPGQGNYAAANAFLDALSHHRRAQGLP ALSIDWGMFTEVGMAVAQENRGARQISRGMRGITPDEGLSALARLLEGDRVQTGVIPITP RQWVEFYPATAASRRLSRLVTTQRAVADRTAGDRDLLEQLASAEPSARAGLLQDVVRVQV 5 SHVLRLPEDKIEVDAPLSSMGMDSLMSLELRNRIEAALGVAAPAALGWTYPTVAAITRWL LDDALVVRLGGGSDTDESTASAGSFVHVLRFRPVVKPRARLFCFHGSGGSPEGFRSWSEK SEWSDLEIVAMWHDRSLASEDAPGKKYVQEAASLIQHYADAPFALVGFSLGVRFVMGTAV ELASRSGAPAPLAVFTLGGSLISSSEITPEMETDIIAKLFFRNAAGFVRSTQQVQADARA DKVITDTMVAPAPGDSKEPPVKIAVPIVAIAGSDDVIVPPSDVQDLQSRTTERFYMHLLP 0 GDHEFLVDRGREIMHIVDSHLNPLLAARTTSSGPAFEAK* Seq ID No 87 >Contig57_027 419 amino acids MW=46737 D pl=5.09 numambig=0 MTQEQANQSETKPAFDFKPFAPGYAEDPFPAIERLREATPIFYWDEGRSWVLTRYHDVSA 5 VFRDERFAVSREEWESSAEYSSAIPELSDMKKYGLFGLPPEDHARVRKLVNPSFTSRAID LLRAEIQRTVDQLLDARSGQEEFDVVRDYAEGIPMRAISALLKVPAECDEKFRRFGSATA RALGVGLVPQVDEETKTLVASVTEGLALLHDVLDERRRNPLENDVLTMLLQAEADGSRLS TKELVALVGAIIAAGTDTTIYLIAFAVLNLLRSPEALELVKAEPGLMRNALDEVLRFDNI LRIGTVRFARQDLEYCGASIKKGEMVFLLIPSALRDGTVFSRPDVFDVRRDTGASLAYGR 0 GPHVCPGVSLARLEAEIAVGTIFRRFPEMKLKETPVFGYHPAFRNIESLNVILKPSKAG* Seq ID No 88 >Contig57_043 492 amino acids MW=52617 D pI=11.54 numambig=0 MAARARKSCPARGSRPAPMRTSPPTSTPTPRPRGWRWTSFTSRRPSASRPAASGSSSGSV 5 RAPSPRGNGSECSTTTLPAEEASWPRRPCRMPTSSCSSPSRSRAALSLHLLPPSSGRRPS GNIALSAALSPPAGPRALPRSPSPSYHPCVLLQRRPRRSNRRAGAALRARQESVLARPAH RWKDRRSMEKESRIAIYGAIAANVAIAAVKFIAAAVTGSSAMLSEGVHSLVDTADGLLLL LGKHRSARPPDAEHPFGHGKELYFWTLIVAIMIFAAGGGVSIYEGILHLLHPRQIEDPTW NYVVLGAAAVFEGTSLIISIHEFKKKDGQGYLAAMRSSKDPTTFTIVLEDSAALAGLTIA 0 FLGVWLGHRLGNPYLDGAASIGIGLVLAAVAVFLASQSRGLLVGESADRELLAAIpALAS WO 00/22139 PCT/US99/23535 186 ADPGVSAVGRPLTMHFGPHEVLVVLRIEFDAALTASGVAEARERIETRIRSERPDVKHIY VEARSLHQRApA*

12. DNA sequence according to any of claims 1 to 5 wherein the DNA is selected from the group consisting of (a) the following DNA sequences: Seq ID No 89 (>Contiglo) GGTAGTGAAATATGCTGTATTCAACAGAAAGCTTGATGAATTGATCTAGA AAGTAGAGCGAGAGAATCAAGTAAGATAGTAGGATGCATTATAAATATAG AATATATACTGCATACGATGACAGCATGCGCACGAATAGAATGCATAAGA GGCAAGCCAATAACCAAAAGTGGAGCCAGAGGAGATAGTCTCGCCAGTAG AAATAATGCTCAGCCAAGCGAGGTTGGACATATCAGTTCCAGAGTAGGTC TCAACCCCGTATATGAGTCCAATGAAGCCTGTCTCATCCAGTTAACGGCC TTTTGAGCAGAGAATCCTCCCTATTTTCGGAGAGGACGCGTCGAATATAA AGCAGGTCCAAAGAAGCAAGCAATAGCCAAAAGTTTGAAAGGTTAGTACG AGCAGCGGCTGGAGGACACTATGGTCGTGCAACGGGGGTAAAGGGTTTCA CGTATTGTAGCAGAGCACGTCAGAGGGTTATTCGTGACATTCGAGGCCAA CGAGGCGGTAGGACTTCGTAAGCGCATGACCATCCCGGTCACAAACGTAG TGCGGAGCGCCTCGTCACGCTCAACAAGGCCCTAGAACGCGCGGCGCAGA TCGACCCTTTTAAACGCCGGCACCGAGCCGGACCGTCCTGCCCAGGTTGT AAAGCGCTCCATCGGCCGACTTATGGCACTCGAGCCAAATCGCCCGGTTC CCCATCGGTCAGCGCAAACGGCCCCCCCGGGCGTCGCCACCCGCGGCGAC GAGGGGCCGTCCAGACGGGTGATCTCTCTCGTGAGCTCGCGGAGAGAGCC TCCTCGCAAGATCGATGTCAGCGGGATCGCGCGCCCCGTCCGCACCTGAA ACGCGTGCTGGAGCTCGACGGCAGCGAGGGAGTCGAGGCCGAACCGCGAT ATCGGCAGCGCGTCGTCGATCTGCCCGGCGTCCAGACGAAGCGCGCGGGC GAGGGTCGAGCGCAGCGCGTCCAGCAGGCTCCGGCCGGAGGGCTCCTCGG TCTCCGGGGGCGCGTCGTCCGGGGGCGAGGCGTCGTCGAGGAGCTCCGGC WO 00/22139 PCTIUS99/23535 187 GCGAACGCGACGTGGCGCTCGCCGAGCGCGTCCTCGAGAAAJGGCGCGCCG GCACTCCCTCCGGCGGACCTTCCCG CTCGACGTCTTCGGCAGCGCGCCCG GCGCGATCAGCGCGACGGCGTGCGCGACGAGCTGGTGCTCGGCGGTCACC GCCTCGCGCACGGCCGCCACGATCTCGCGCGGATCCGCGGCCACGCGCGG GTCGACCTCGCACACCACGGCGAGGCGCTCCTCGCCCTCGTGCTCCACGG AGAACGCGGCGCTGCAGCCCGGCCGG-ACGGCGCGATGGCTGCTCTCGACG GTCTTCTCGATGTCCTGCGGGAAGTGGTTGCGGCCTCGAAGGATGATGAG GTCCTTCGACCTCCCCACCACGAACAGCTCGCCGCCCCGGAGGAAGCCGA GATCTCCCGTGCGCAGGTAGCGCGGC-GCCGCGCTGCCAGCGAGCGTGGCC CCGAACGTGGCCTCCGTCTCCTCCGGGCGCCCCCAGTAGCCGACGGCTAC GCTGGGCCCG-GACACCCAGATCTCC-CCGATCTCCCCCGGCCCGAGCTCGT TCCCCGCGGOATCGACGATCGCGAC C-GCCCGCGGATCGAGCGCCCGACCG CTGCCGACGAACACGCGCGCGCCCTCCGCCGCCGACGCGACGGCGCGCCC GAGCTCCACCTCCTCGGGGGCGAGGCGCGCCAGCACCGGCGCCTCGGCCC D CGCTCCGCCGCTCACGATGAGCGTLGGCCTCGGCGAGCCCGTAGCAGGGA TAGAACGCCTCTCGCCGGAACCCGC TGACCGCGAGGCGCGCGCGAAGCG ATCGAGCGTGTCGGCGCGCACCGGCTCGGCGCCCGTGAACGCGACCTCCC ACGACCGCAGATCGAGCGCCGCTCGCTCCTCCTCCGAGCTCTTCCGGACG CACAGGTCGTATGCGAAGTTCGGGCCGCCGCTCACCGAGGCGCCGAGCGC CGAGACGGCGCGGAGCCACCGCATCG---GCCTCTGCAGGAACGAGAGCGGCG ACATGAGCGCGACGCGGATCCGCCGG-1-TAGAGCGCCTGCAAGATCCCGCCG ATGAGCCCCATGTCGTGATACGGCGGCAGCCAGATCACCCCGACCGGATC CGGGCTCGTCAGGTCGAATCCATGCGCGATGAGCCGCGAGTTGTGCAGCA GATTCCCGTGGGTGAGCATCACCC CCTTGGGCTCGCCGGTCGAGCCGGAG DGTGTATTGAAGGAACGCGACCGACrnCCGGCCGGAGCGCCGCGCCCGGCCC CTCGATCGGGCCCGGCGACGGGCCG-TCGGTCGCGATCCACCGGAGCCGCT GCAGCGCGG""'CGGCCGCGGCGCTGC-CC-GGCAGGGACGCCACGATGCCGGCG ACGGCCGATGACGTGAGCGCCGCCTC -GGCGCGCGCGTCCGCGACGATGGA AGCGACGC".GCGGCAGCGTCCGCTCGk-AGCCGGCCGAGATCCGGCGGATAGG DCGGGCACGGTCCGGACTCCAGCGTAAAGACACCCGAAGPACGCGGTGATG WO 00/22139 PCT/US99/23535 188 TACTCGATCCCCGGCGGATACAGCAGCAGCGCGCGGGCCCCGGGGGCGAC GCCCGATGCCTGCAAGAGGGCCGCGACGGTTCGCGCGCGCTCGTCAATTT CCCGCAGGGTCACCCAGGTCGCCCCGGCCTCGACGTCGCCGGACTCAAGA AAGCAATAGATTGGGCGGGCGGGCTCAGCTTCGGCCCGCTGGCGCAAGAG 5 GTCGATAACGGTGGAAGGGCGGTTCCGTTCGTTCCGTTCCAATGCAAGAA AAGCATCATTCATTGAACAGACCCCTCCGCCGCGGAGATAGCAGCTTGTC CGCTGCGACACAACCGCCGCGCGACGCGCGTGGCACGGCGGGATCCGGGC GTTACTCCACCTGCACTTCCCGTCGCGTCACGCTCGCTCCGCCGCGGGTG TCGTGAACCACCGCCCACAGCGACACGCGCCCTGGCTCCGAGGGCGGCGT D CCACGTGGTCCCGTTGCCCCCGCGGGAGGCGCCGGTCGTATCGCTCACCA GGCGGCGCGCCCCGTCGAACTCGCCACCGTCCGTGTAATAGTCGACCCAG ATCGCCTCGCGCGCCGGTGGACCGCCGAGCCCGGCGGCTTCCTCGTCCAC CTCGGCGGCCTTCTCGGGCACGACAGCCTCAATCTCATAGGTCGTGCACT CGTCCTCGGCCGGCTCGGTCCGGCCGCAGCCTTGGGCCTGCTCCTCGGAC 5 CGAACGCACCGCTTCACGACGGGCAAACCGTCCTCGCCCGGCGCGACCTC ATTGCCATCGAGCTTCAGCGTGAAGCCGTCGATGGGCGGGTTCGTGTTCA GCCGCTCCTTCTTGAAGACATAGACCTGCGTGTAGCCCACGACGAAGCTG TCCGGACCGAGCACCGTCCCGTCGTCGCCGACGCACTCCAGCGGAAACCC GGCCGTTTCGGGCGCCGAAGCCACGCGTGTCGTGCCGGCGCACACGGCGA ACAGCACGTAAGCCGACGAGTACACCGTCCCCGTCTCGGTGGGCCTCGCG TCCTTGAGGATCTCCTTGGGCAGCTTCCACCCGAACGAGACCGCATCGGG CTCGCCGCTCTTCTCCGGACCGATCTCCTGCTGCGCGAAGGGGACGGTGC GCTCCCCGTCGCCGCTGCCGCTGCCGCCGTCGCCGCTGCTGCCGCCGTCG CCGCTGGCACCGCCACCGCCGCCGCCGCCAGCGCCACCATTGCCGCCTTC D GCCGCCTCCAGCGCCACCACTGCCGCCGTCGCCGCCGCTGCCACCATCGC CACCACTGCCGCCGCCGCCGCTTCCGCCGCTGCCGGCCGGCACCGCCTCC CGGATTCGCGACGATTCCCACCGCATAGGTGCCCAGCCACTGCGGGATGC ACCCGAGGTGCTCGTCCACCCCGACCGGCGGATTCACGCAGCCGCCCACC CACGTGACCTCGACCTTCCGCGGCGCGCCGCCCTCCGCGCCTTTCGCGTC D GGCGTACGTCATCCGGAACGTCACGAGCTCTTCCGCCGCCGCGTACGGCT WO 00/22139 PCT/US99/23535 189 TGTCCGCCGTCACGGCGAGGACGCGGAGCCCCTTCACCTCGGACGAAGGG GCCATGTCGCTCCCGGCGCAGCAAGGGATGCCCACGGCCAGGGTCGAGAG CGCGGCCAGCAGCGCGCGACGAGCGGGCAGTGCGGTCCGTTTCATCAGAA ATCTCCTCGCAGCCCGAGCGTGGGCAGGAAGGGGAGCCCCGTCACGTACT 5 CCCGCTTCGTGTAGTTGAAGTTGTAGCTGATGCCCTCCGCAGCCATGTAA TTGTAGACGTTCTGGATATCGAGGTAGAGCCCGAGCTGCCACCTCTTGAA TTTCCACGTCTTGTCGGCGCGGATGTCGAGCTGGTGAAACAGCGGCATCC GCTCGCTGTAGTCACCCCCGAGCGGGATCGGCGAATACCTCGCCGAGGAC GCGTGGTAGATCGCGTTCACCCGGTTCGGATTGCACCCCTTCTCCTCCGG 0 ATCGCAGACATAGGGCGTCTGCAGGTTGCCCGACACGAGCCGGAAGCGCG CGCCCAGCTCCCAGCCCCGGCCGAGCCGCAGGCTCCCGAGCACCGTCAGC ACGTGCGTCTGATCGAACTGGGTGAGGTGCTCCTCCTCGTCGGGGCCGTC CTTGCGCACCGACCGCGAGAGGGTGTACGCCGCCCAGCCGAAGAAGCGCT CGTCCGGCTTGTACTTCAACAAGAGCTCGCCGCCGACCGCGTATCCGGTG 5 CCATCGTTGGCATAGTCGTCCTTCTCCGGCGAGAAGACGACCAGCCGATC GAGCTGCTTGTAGAACCCGTCCAGCGTCACCTCGATCTGCGGCGTGATCT CCTGCTCCACGCCGAGGCCGTAATGCACGGCGCGGTTCGACTTGAGCTCC GCATTGCCGAACGGCTCGATGCTCTCCGCGAACTGCGGCGCCTGATAATA AAGGCCCACGCCCCCCTTGGCCGTCGTCCGCGGGAAGCCGCTCCGGATGT 0 CGTAGCGCGCGTTGACCCGCGGGCTCACGTCGAGCGTCTGCGTATCGAGC GCGTAGTCGACCCGCACCCCGGGGACGATCCGCGCCCGCGGCGAGGGGAC GACCTCGAGCTCGGCATACGCCGCGGGCCGCGAGTACGCGCCGTCGAACG ACCGATCCTGGAACGGGTACGTCGAGAACGGCTGGTTCGACGGGTGGCCC GCGGGCTGCTGCGACGGCGCGCGGATGTTGACCGTGGCGACGCCGCCCGA 5 GAGGTCGGTGCCGACGTTCATCGTGAGGTACCGCGCGAACCTGTGCGAGA GCTCCAGCCGCAGGTCGAGCGAGGTCGAGACGACGTTGAAGGCGAGGGGA GAGATCTCGAAGTCGGCGATGTCCCGGCCGAGCGCCATCGACCACAGCAG CCGATCCCGGCTCCCGATCCGGTTCTCGTAGCTGAGCTGGAAGCGCTGGA AGGCGGTGTGCAGCCCGAAATCGCCCGTCAGCGCCGGCTCGTCCTCCGGC 0 GGCTTGTCCAGGGTGATCTTGAAGGCGTCGTCCGATCCGTAGAAGCTCGC WO 00/22139 PCT/US99/23535 190 GCGCACGCGCTCGCTCGCGGAGGGGCGGCCCTCGAGGACGAACTGGTAAT CATAGTAGACGGGCGCCTGCGTGACGCTGGAGCCCGCCTCCTTGAGCACG GGCCCGAGCCACGCGTCGACCCAGCTGCGGCGGCCCGCCGCGATGAACGT CCAGTCCTTGAGGAACGGGACGGGGCCCTCGAGGAGCACGCGCCCGTCGA TGAGGTCGAGCTGGACCACGCCGTGGTACTTGCCGTCCTGCTTCGGCGAG CGGAGCCCGACGTCGACGATGCCGCCCATGGCGCGGCCGTACACGGCGCT GAAGTTGCCCGGATAGAAGTCGATCTTCTCGAGCATCTCGGTCGGCACGA CCGAGGAGAGGCCGCCGAAGTGGTAGATGATCGGCACCGGGGTGCGATCG ACGAACGTGAGCGTGTCCTGGGGCGCGGACCCGCGCACGATGAGCAGCCC GAAGCCGCTGCGCGCGACGCCCGGCAGGCTCTGCAGCGACCGCAGCGCGT CGCCGCCGGTGCCGGGGATGCGGT CGATCTCGCGGCGCTCGATCGTCCTC CGCGTCACCTCGCGCGGCGGGCGCTCGCCCTGCACGGTCACCTCGATGCC CGGCGCCTTGCCGTCCTGCGGCGCGGCGAGCGAGATGCGGTAGCGCACCT CGATCGCCTCGCCGGCCGCGATCTCCTCCTCGGCGGCGAACGGCTCGAAC CCCGCGGCGGCGACCTCGACGCGGTACTTGCCGGGGGGGAGATTCTTGAA GCGGAACTTGCCGCCCTGGTCCGTCTTCGCCTCCTCGCGGCCGCCGTCGG GGCGCACGAGGGTGACCGCGATGTCCGGGAGCGGCTCGCCGGTGCCCGCG GACAGGACGGTCCCGACCACCGTCTCGACGTCGGCGGGCGGCGCCGGCGC GGCCGCATCGGCGGGCTTGGGCGTGAGCGTGAACGCGTACCGGTAGAGGA TGCGCGCCGCCGCGGGCGTGCCGTCCGGGCGCCGCGCCGGCGCGAACTCC AGGCCGGGCGCGGCCCGCGAGCGCCGCCTCGTTGAAGCCGTGCCCGCCGG GCGTCGCGACCTCGGCCTTGGTGACGCGCCCGGTCTTGTCGATGTCGAGC TTGAGGATGACGCTGCCCTCGACGCCGGCGCGCTGGGCCTCGATCGGATA CGCGGGCGGGGAGTACTTGATCAGCGTCGGCGGGCTGATGGCGGCGGGCG CCGGCGGGGGCGCGCCCGGCTGAGGGACGACGACCGCGCCGGCGCCGCCG CGGGGGACCGAGGCGCCGCCCGAGTCGCCCTCGGCGGCAGGAGGAGGCTC GGGCGGGGGCGCGCCGGCGGGCTGCGCGCGCGCTGCGCTGCCGGTCATCG CGACCGCGAGCAGCAGCGCTTCCGAGACGACGAGGCGCATCACGGAGGAC GCTGTGGAAGGCATGCGGCCCGCCCTCTCGCATGGCGAGGCCGAGGCGGA AAGACGCATCGCGCAGCCAGGACCGTGCTTCACATTGCTTCACACAACGG WO 00/22139 PCT/US99/23535 191 GCGCCGCGCGCGCTCCCGGGCCGCGCGAGCGCAGGCGGCGCGCGCGCCCG CGGGCGGCGCGATCGCGAGCGGCGCGCGGTGCGATCAGCCGCCGACCTCG GCCACGAACCGGCTCACGTCGTCGCTGTCGCCCACGAGCAGCAGCGTGTC GCCGTCGCGGATCACGTAGTCCGGTGTGGGCGCCTCGAGCCGCGGCTTGT 5 CGCCGGGCCGCTTGTTCGTGTGCGGCCGCACACCGAGCACGTTGATGCGG TACCGCTGGCGGATCTTCGAGCCGGCCAGCGTCTGCCCGACCAGCGGCCC GTGGGCGTTCCAGGGGACCACGCGGTAGTGGCTCGCGAGGTCGAGGAGGT CCTGCGCGAGCGGCATGGTGATGTCGGCGCCGACGCGGCGGCCCATCTCG GTCTCGAGCTGGATGACGCGGGTCGCGCCCACCGCGCGCAGGATGTCGGC 0 CTGGCGATCGGTGGCGGCGCGCGCGATGATCTCGCGCACGCCCATCCGGA CGAGGGAGGCCACGCAGAGCACGGACGGCTCGAAGTGCTCGCCGAAGGTC ACGATCGCGGTCTCCACGTACTGCGCGCCGATCCCCTCGAGCACCTTGTG GACGGTGGCGTCGCCGACGAACGCGGCCGAGGTCTTGTCCTTCACGGCGT CGACGGCCTCCGGGTTGTTGTCGACCGCGATCACCTCGGCCCGGTTCTTC 5 CAGAGGGTCTCGACGACCGACGTGCCGAACCGCCCGAGCCCCGATGACGA GGACGCTCTTCGATTTCATGGTCTCCGGTCGCGCGCCGCCCCCTCGGGGC GCGGCGCCGCGAAGGTCTCACGGATGCGCCGGGAGCGCCACGGTTCGGCG CTGCCGTCGTCGCGACGGCGCGGCCCGCGCGGGCCGCGCCGCGCGGCGCT CAGTAGAGCTCGTCCTGGTGCTGCCACCGCTCCGAGATCCACGCCTTCAG D GTACGCGATCTCCTCCTCGTACGTCGTGAAGTCGTCGCGCCAGCTCCAGC CCTCGTAGCTCCGGTACGCCTCGCCCoACCGCGCCTCGTCCCGGCGCGCG CTCGCGTCGATGCGCTCCACGTAGCCGTCCACGATCGCGTGGATCTCGGC CTCGGCGAGCGCGCCGCGCAGGAC CTGATCGTAGCGGGCGCGCAGCGGGT CGCCGATCGACGGCTCCTCGAGGAGGCGCTCGAAGAGGAGGTTCACGTCG 5 CGGTAGTCGACGCGATCCGACGCCGGCTCGCGCTCGGTCTCCCACGACTG GCCGAAGCTCGCGTTGAAGTCCCACGGCGCGTAGCGGAATACGCCGTCCG CGGCCGGATCGCGGTAGTGGTAGCTGTTCTTTCCGGCCGAGTCGTTGGCC ACGATGAACGTGACGAAGATCCACCAGTCCTCGTAGTCGCGCAGATCGAT CCGCGACCCGATCTCGGCGGCGAACGTGGCGTCGTCGGACTCGGCCACGA D AGCTCACGAGATCTTCCAGATCCGAGAACGCCTCCGGCTCGCCCTCGGCC WO 00/22139 PCT/US99/23535 192 GGCGCCCCTTCCTTCTTCTCGAAGCCGTCGTGCAGCGTGTCCTTGGGGTC GCCGGACCGGTCGGTCAGCGCGAAGTTCGCGTCGTGGCTGACCGCCTTGT AGAGGTTGCCGTCCTGCGGGTAGCCGTGGTCCTCCATCAGGTAGCCGTCG ACGTGATCCGCGACGGTGTAGAGCCCCGCGTACTCCCCGTCGAGGTACAG 5 GACGGCGCTGTAGGTCTTGATCTGGATGTGCTCGGGATCGAGGCGGTTCC AGAGGTCATAGGCGAGGCGCTGCCGGACATAGGAGTTGTCGTCGAACGTC GTGATGAGCACGACCTTGCGGCGATCGGTGAGCCGCCCGCCTCGTCGGG CTCGTTGAACTTGTCGTCCTTGGGGAACTTGAGGGTGTAGCTCCGCTTCG GGTACGAGAGCGAGCTCTCGCCGCGGAGCTCCGCCTCCGCGGCGTACGTG D TGGCCGCGGTAGATCACCGTGGCCGGGGCGTACTCCTTGTCCTCGGGGAC GGGCGAGAGGAAGAGCACCGGCAGGCCGTACTCCTCGGGGTAGCGGGTCG GATCGACGACGGGCACGTTCGACGGATCGGCGAAGGCGTCGGCGACGCCG ACCTTGACGCGCCCGACCTCGGACGTCTGCGCGACGCGGATCTCGATGTC GTAGACGGCGGCCTGATCGAGCCCGGGCGAGAACGTCACCTCGCGCGCGA D TCGGGTCGTACGCGGCGCCCTCGGGGAGCGGGCCGACCTCGAACGCGTCG CCGGCGAGCGCGAGGCCGCTCGCGCACGTCACCGGGAACGTCACGGTCTC CCCCTCGAGGAGCCAGTGCGGGCCGCCGCCCGACGGCTGGCAGCGCGAGC CCTCGGCGCTGGAGCCCCCGCCGCTGGAGCCGGAC D Seq ID No 90 (>Contigll) GGCGACCCCACATATCACATAGTAGAATCAGTGTGAGTTAGACAAATGTC GAGTGATGAGAAGGACAGAAGTGAGAACTCTGTCGATCACTGTAGAACGA GAGAGTATGAGCCTGCATACATGATAGCGGACATGAGAACGAGTGTANTA TGATGCTACTAAGAGAGTAACAGATCAGAGACTAGAGTAGAGCAATAGAA D NTCAGAGATAAGTCAATGACGAGGAGTAGTGATAGAGCTCTTAATAATGG CTGAGGTCGAAGATAGAAGTGCATAGAGCGATAGATATACAATCGGTTGA AGCAGAGAGTAAGATAAGATCAGACACNGAGTACAGAGAGAGACGAATAG ATGGCGTGATNTCACAGAGAGGTGCGAGCGTAGCTGACGAGAGCAGAGAC GCAGAGTAAGTCACACCTAGATAGTTACGGCGAGAGACAAATGATAGGAA D GGAGTGGACGAGATCAACAGNCCGGAGCACAAGAACGTGAGATGCGACCG WO 00/22139 PCT/US99/23535 193 TGTAATAAACAGGAGACAAGAGCGACTACATAAGAGAGCGAAGCGAATAG ATAAGATATAAGCCCAGAGCAAAATAGAAGGAGAGAGAGAGTATTTGTAA TAAAGCAACAAGACGGAGAGAGCGAAGCAGCAGGCAACGATTAGAAGAAA GACGACAGGAAAGTGAAAGCGAAAGAGAGCAGGTAGAAAGAGAACCAAAA 5 AAGCACGAAGGAAAAGGAAGCTTCTATGATAGGTGCGGGACAAGGCGTAG CTACAGGAGACAGCCGGCATACGAGGAGCCGGTAAAAGCTAGCCTTTCAG AACACATCGGGAGCGCGTAAAGGCGGACCACGCTCGACGGGATCATGTAC GCCGACAGCGACGCCTTCAGCCCCGCGCGCACGTCCGGCGCGTCGCCCGC CGCGTCGCCGTCGAGCACGACGTAGGCGACCAGGCGGGCGTCGCCCGGCG ) CGTCCTCGCGCAGGACCACGGCCGCCTGGCCCACGCCGGGCACGCGCCGG ATCTGCGCCTCGACGTCGCCGAGCTCGATCCGGTGCCCCCGGAGCTTGAT CTGGTGGTCCGAGCGGCCCTGGAACTCGAGCATCCCGTCGGGCAAGAAGC GCGCGACGTCGCCGGTCCGGTACATCCGCCCGCCCGCGGCGCGCGCGCAC GGGTCGGGCAGGAAGCGCTCCGCGGTGAGCCCGGGCTGCCCCACGTAGCC D GCGCGCGAGCGGCGCGCCCGCGATGTAAAGATCGCCGAGCGCGCCGATGG CGGGGCGGCGCATCGCGCCGTCGAGCACGAACACCTCGGCGTTCGCGACC GGCGCGCCGAGGGGGACCCACGTGACCCGCGGGTCGCTCGGCAGGACGCA GCCGGTCACCGCGATCGCGGCCTCGCTCGGCCCGTACATGTTGATGAGGT CGCCGTCGTGCTTCGCGTAGAAGCGCCGGACGAGATCGAGCGGCACCGCC D TCGCCGCCCACGAGGACCTTCCGCAGGCTCGCGGGGAACGGCTGCTCGGG CCCCCCGAGGAACGCCGCGAGCATCGAGGAGACGAAGTACGCGGTCGTCG CCCCCTCGTCGCGCACGAGGCGCCGAAGGTACTCGGGATCGCGGTGCCCG CCGGCCCGGGCGACGACGATCCGCGCGCCGAACGAGAGGGGCCAGAAGAT CTCCCAGACGGAGACGTCGAAGCCGAACGCGGCCTTGAGCAGGACCCGGT D CGTCCGCGGTGAGCGCCCAGTACCGCTGGATCCACTGCATCTGGTTGACG ATGGCGCGGTGGGAGATGAGGCTCCCCTTCGGCGTGCCCGTCGATCCGGA CGTGTAGATGACGTACGCGCCGCTGTCCGGCGGCGGGCTCACGGCGGGCC GCGCGTCGGAGCACGCGGCGATCTCGGCGGCCTCGGCGTCGAGGAGCAGC GTCGTCCAGCCGCCGGTCGGGAGCTCGTCGGCGATCGCGTCGTGCGTGAC D GAGGAGGCGCGCCCGCGCGTCCCGCATCATGAAGGCGAGGCGCTCGCCGG WO 00/22139 PCT/US99/23535 194 GGTACTCGTGGTCGAGCGGCAGGTAGGCGCCGCCCACCTTGAGCACCGCC AGGGTCGCGACGACCATGTCCTCGGAGCGCGGCACGCAGACCCCGACGAT CGTGTCGAGCCCGACGCCGCGGCGGC 'GCAGGCAGCTCGCGAGCCGGTTCG CGCGCCGCTCGAGCTCGCCGTACGTGAGCGACTTGCCCTCGCTGCGCACC 5 GCGACGACGTCGGGGTGCTGCTCGGCGCGCTCCTCGAACCACCGGTGCAG CGCGCAGGCCGACGGCAGCTCCATCGCGGGGCCGCGCGACCACGCCTCGA TCTCGGCGCGCTCGCCGGGGCCGACGTACTCGCCCTGGGCGACCGGACGC TCGGGGTGGCGCGACAGGTCCTCG -AGCAGCGCCGCGAGGCGCTCGGCGAG GCGCTCGGCGTCGCGGCGCGCGCC-GG-CCGACGCGTCGTAGCGGAGCTCCA 0 GCGACGCCGACGGGCCCGCGCCGGC-GCAGTGCAGCCGGCAGGCGACCTGG TCAGACGTGCTCCAGACGTCGAGCACGCGGGCCCGCGCGCCGTCGAGCGA CAGCGCCGCGCGGCCTCCGCGGCG-'GAGAAGCCCCCAGCTCATCCGGTGG CTCACCCCGGGCGCGGCGTCCTGGTGCGCGGCCGCCTCGGCCTCGGCGAG CGCGAGCCGCCGCGCGACGTCGGCGAGCGTGTCCGAGGCCGAGATCTCGA 5TCCGCACCGGCAGGAACCGCGCGAJACGGCCCCACCGCGCCCGCGAGCGCG TCCAGCGACCGCCCGTCGAAGCGGACGGCCACGGTGACCTCGGGCTCGTT GCCGCCGCTCATCCGCCACAGGAGCGACGCCCACAGGGCCAGGAGCACGA TCCGCTGCGGGACCTGCCACGACG,"ACGACCAGCGCTCGACCTGCGCCATC CCGCCTTGTCCCAGATCGACCCGCG CGCGCCCCGAGCCGGCGCCGGCGCC D GGCGCCGCCGCGGCTGAAGGCGAGG3--TGGAGCGGGGGCCCGAATG""CGAGC GGCGCTCGGCCCAGAACCTGCGCCCG TCGCCGGCGTCCTCCGAC-TCGAGC ATCCCGTTGAGCCACTCGGCGACGTCCGCGTACTGCTGCTCGGGCGGCGC GCCCGCGCCCGCGGTCGACGCGCAGAGCTCGCGGACGAGCGGGG"CGATCG ACTCCTCGTCGACGCACCACGCGGGCGCCGCGAGCACGAGCCGGCGCTCC 5 TCCGGGCCGACGCGGACCAOGCCGACGCGCAGCCCGTCGTCCGCGCCGCG GTCCTCCGAGAGGCGCGCGACGAGC-CGCGACATCCGCTCGCCCTLGCTCGG CTTCGGAGCACCCGACCCAGTCGTC-CTGCTGACGCCCACGCGAAGCGCGG CTCGCCGACCACCTGCGCGGCCTC-GCCCGCCCCGCCTCGACGAG-'GCGCGT GCGCAAGATCTCGTGCCGCTCGGCC'-AGCGCGAGCGCCGCCCCGuAGAGCC 0 GTCCCTCGTCGCACGGGCCGGTCACG2-:GCGAC GACGGCCAGCGTC-CGGCAC WO 00/22139 PCT/US99/23535 195 CCGGGCGCCCCCGCCTCCCGGTCGAGCGCGCGGATCGCCCGCTGCTGCGG CGAGAGGCTGAAGCCGGTCATCTCGTGGTCACTCATCCAGGTCGTCCTTC GGTGAGGTCTTCGCTTCGCCCGGCGCGCCCGGGCGCGGGAGGGTCACGGC GCGCCGGCGCGCGGAGGTCAGCTTGTCGAGCGCGGCGCCGCGCGCGGCCT TCCGCTCGAGCTCCCGGCGGGCCGCCGCGGCGCGCTCGAGCTCCCCCCGG AGCTCCGAGACCGGGGTGTCCGGCCGCGCCGTCGCAGTGGCCAGGATCTG CCGGTAATCGCTAAGGAAATTGTCGACCGTCGCCGCCCGGTACAGCTCGC TGCTGTGCTCGACGCCGAAGCGGAACGAGCCGCCGGCCTCGGCGACCGTG AGGACGAAGTCGAACGCCGTCGTGGTCGCCTCGCCCTCCAGCGCCTCGAG CTCGAGCCCCTCGAGCTTCATCGGGGGGACGTGCACGTTGCGCATGACGA ACTTCGCGTCGAAGAGGGGCACGTGCCCGACGGCCCCCTTCGGCCGCAGG GCCTCGACGAGCCGGTCGAACGGCAGGTCCTGGTGCTCGAACGCCTCGAG CGCGACGTCGCGCACGCGGCGGACCAGCGCGCCGAACGTCGGGTCGCCCC CGCAGTCGGTCCGGAGCACGAGCTGGTTGACGAAGAAGCCGATCATCGGC TCGGTCTCGACGCGGTTCCGGTTCGCGACGTCGGTGCCCACGACGAGGTC CTCGAGCCCGGTGCGCTGGTGCAGGACGAGCTTGTACGCGGCGAGCAGGG CCATGAAGGGGGAGATCGCCTCCCGCTCGCAGAACGCCTTGATCTGGCGG GTGAGCTCGGCCCCGGCGTCGAGGCTCCGCCGCGCCCCGCGCCACGTCCT TCGCCCCGCCGGCTCGTGGTCGACCGGCACGCGGGCCCGGCGCAGCGCGC CCGAGAGCTTCGTCGTCCAGTACCGGAGCTCGCCCTCCAGGACCTCGCCG GACAGCCACGCCCGCTGGGCTGCGGCGAAGTCGACGTACTGCGCCGGGAG CTCCGGCAGCCGGGAAGGCTGGCCCTGCGCGAAGCCGCCGTAGAGCGCGG CGAGCTCGCCGACGAAGACGCCGACCGACCAGACGTCGAACACGACGTGG TGCACGACGAGCGCGATGACGTGCTCGTCGTGGCGCTTCCGGATGACCCG CACGCGGAGGAGCGGCCCGCGGCTCAGGTCGAACGGCGCGAGGCTCTCCT CGAGGACGAGCGCCGAGACCGCCGCGTCGAGGGCCTCGCCCGCGAGGTGC TCGAGGTCGGACATCCGGAACGGCACCCGGGCCTCGGGCGCGACGACCGG GAACGGCACGCCGTCCCTGGCGCTGAACGTCGTCCGCAGCGCCTCGTGGC GCCGCGCGATCTCGAACAGGCTGCGGCGGAGCGCGTCGACGTCGAGCCGG CCCGTCGCGCGCACCACGAACGGGATGTTGTACGCCGGGCTGCCCGGCTC WO 00/22139 PCT/US99/23535 196 GAGCTGATCGACGAACCACAGCCGGTGCTGCGCGAACGACAGCGGGAGCG GGCCGTCGCGGGGGATCCGCGCGATCGGGGGGAACTCGCGCCGCCGCGCC TCGCCGCGGCGCGCGGCGTCGACCTGGGCCGCGAGCGCCGCGACCGTCGG CCCCTGGAAGAGCGCCCGCAGCGGGAGCTCGACGCCGAGCTGCGCGCGGA 5 TCCGGGACATCACCTGGGTCGCGACGAGCGAGTCGCCGTGCAGGCCGAAG AAGTCGTCGTGGACGCCGATCTCGTGGACGCCGAGGAGGGCGCTCCCAGA TCGCGGGCGATCGCGCGCTCGGACTCGGTCGACGGCGCGGCGAACGCGGC CCCGGCGTGCGCGCGGGAGACCGCCGACGTCGGGAGGGCGTTCGGCGCGG GCGCGAGGGGCGCGTCGGCCGGCGCCGGCTCGGCGGCGGGGGCGCCGCGG 0 CGCGGCGCGATCCAGTGCCGCGCCCGCTCGAACGGGTACGTCGGCAAGCG GACGAGCGCGCCGGGGGACGCCCCCGCGGACGGGCCGTCCAGTCGACGGC GTGGCCCGCCTCCCAGAGCTGGCCGAGGGCCTCGGCCAGGCTCGCGGGCT CGGACGCGGCGTGGGTCGACCCGAGGCTCGCGATCGCGGCGCCGCCGCGC CCGGCCAGCGTCTGCCGCACCAGCGTGGTCAGCCCGCGGCCGGGGCCGAC 5 CTCGAGGAACAGGGCGTGCCCGGACGCGAAGAGCGCCTCGACGCCGTCGC TGAAGCGGACCGGCTGGCGGAGGTGCCGCGCCCAGTAGGCCGGATCGGTC GCCTCGGCGTCGGTGAGGAGGGCGCCGGTGACGTTCGAGACCACGGGGAT CTCCGGCGGGGAGAGCCGCGCGCGCCGCACGCTCTCGAGGAACGGGGCCA CCGCGCCGTCGATGAGCGCGCAGTGGAACGCGTGGGACGTCTGCAGCGGC D CGGGCGAACACCTCGCGCGCCTCGAGGCGCGCGGCGAGATCGCGGATCGC GCTCGCCGGGCCCGCGACAACCGTGAGCTTCGGGCTGTTGACCGCGGCGA TCTCCAGGCCGGCCTCGAGGAGGCCCTCGACGTCCGCGGCCGGCAGGCCG ACGGCCAGCATGCTCCCGGCCGGCGCCGCCTGCATGAAGCGCCCCCGATC GATGACCAGGGACATCGCGTCCTCGAGCGTGAACACGCCCGCGACGCAGG 5 CCGCCACGAGCTCGCCGAGGCTGTGGCCGATCATCGCCGCGGGCTCGATC CCCCAGCTCATCCAGAGCCTGGCGAGCGCGAGCTCGACGGCGAAGAGCGC GGGCTGCGCCAGCGCGGTGCCGAGCAGCGTGCGCCCGTCGCCCTCGCCCT CGCGGAAGACGACCTCGCCGAGATCGAGGCCGCGCGCCCGCGCCGCCGCC GCGCACGCGTTGAAGGCGCTCCGGAACGCCGCCTCCTGCGCGTAGAGCGC 0 GCGGGCCATCCCGACGGCCTGCGCGCCCTGGCCCGGGAACGCGAAGACGG WO 00/22139 PCT/US99/23535 197 GCGCGGCTCATCGGGGCGCGCGAGCGCGCTCGCCCCCTCGCGGGCGAGCC CCTGGATCGCCTCGGCGCGCGTCCGGGCGACGACCGCCCGGCGGTACGGG TGCTCCGCGCGCCCGGTCTGGAGGGTGAACGCGACGTCGTCGAGCGGGAC GTCGGTCGCCTCGAGGTGCGCGGCGAGCTGCGCGCAGGCCGTCGACAGCG 5 CCTCCGGCGTGCGCGCCGAGAGCGTCAGCACGTGATCGCGCTCCGGGGCC GGGGCGCGGGGCGGCAGCGGGGGCGGCTCCTCGAGCACGACGTGCGCGTT CGTCCCGCCGATCCCGAACGAGCTCACGCCCGCGCGGCGCGGGCGGAGCT CGCGGGGCCAGGGCGCCGCCTCCCGCGGGACGAAGAACGGGCTCGCCGCG AGGTCGAGCTTGGGGTTCGGCGCCTCGAAATGGACGCAGGGCGGGATCTC 0 GCCGCTCCGCACGACGTGCGCCGCCTTGATGAGGCCCGCGACGCCCGCCG CGGCGTCGAGGTGGCCGATGTTCGCCTTGATCGAGCCGAGCGCGCAGTAC GCCTTCCTCGGGGTCTTGCGGCGGAAGGCCTGCGTGAGCGCCTCGACCTC GATCGGATCGCCGATCGCGGTCGCGGTGCCGTGGGCCTCGACGTAGCCGA TCGAGCCGGGATCGACGCCGGCGACCGACTGCGCCTCGGAGATCGCCGCC 5 GCCTGGCCGTCGACGCTGGGCGCCATGAAGCCGACCTTGCGCCCGCCGTC GTTGTTGACGGCGGAGCCCCGGATCACCGCGTGGACCGTGTTTCGGTCGC GGAGGGCGTCCGCGAGGCGCTTCAGCGCGACGATGCCGACGCCGCTGCCG CCCACGGTCCCCTCGGCGCGCGCGTCGAACGGCCGGCAGCGGCCGTCGGG GGAGCAGATGCTGCCGGGCACGTACGGATACCCGCGCTTCTGCGGGATGC D CGATGGAGACGCCGCCCGCCAGCGCGAGATCGCACTGGCCGCCGAGGAGG CTCTCGCACGCCATGTGGACGGCCACCAGCGACGTCGAGCACGCGGTCTG CACGACCACGCTCGGCCCGTGGAGGTCGAGTTTGTACGAGACCCGCGTCG CGAGGTAATCCTTCTCGCTCGCCAGCATGAGCGCGTGCGGATCGACGGTG GCCGCGAGATCCGGGTGCGAGAGGAGCTGGAGGAGGTACGTGTTGGAGCC 5 GCACCCCCCGAAGACGCCGATCGCGCCCGGGAACCGGGCCGGATCGCAGC CGGCGTCCTCCAGGGCGGCGACCGCGCACTCCAGGAAGAGGCGCTGCTGC GGGTCCATGAGCTGCGCCTCGCGCGGCGAGTACCCGAAATAGGACGCGTC GAAGCGGTCGATGTCGTCGAGCAGGCCGCCCGCGCAGACGACGGGCGCCC CGGGGGCCGCGCTCGCGCCGACCGGCGGCTCCTCGCGCTCGCTCTCCGGG 0 AAGCGCGCGATCGACTCGACGCCGCGCCGCACGTTCTCCCAGAGGGCGTC WO 00/22139 PCT/US99/23535 198 GACGCTCGGGGCGCCGGGGAAGCGGCCCGCCATGCCGACGATCGCGATGT CGCTCCCCCCGTCCTCGGTCTCGATCGGCTCTGACATGGCTATCCTCGCC CCCGGCGGCGTCGCGCGTCGCGGCGCGCCTCGGCGCGCTGCGCCCCGACG TCGGCCGGCTCGGCCTTGACCGTCGCCGCGTCGAGCCGCTGCGCCAGTTG 5 CTCGATGGTCGGGTACTGGAACAGGTCGGTCAGCGACACGGCCTGCGCCG CGGCGCCCTCGTCGGGCGCGCGCGCCGCGATGCGCTCGGCGAGCAGGCGC TGCGCGCGCACGAGGAGCAGCGAGGTGAAGCCGAGCTCGAAGAGGTTGTC GGTCACGCCGACGGCCTCGACCTGCAAGACCTCCGCGAGCACCGAGGCGA TGAGCCGCTCGGTCGCGGTCCGCGGGGCGACGGCCGCGGCGCGCGGCGCG 0 ACCGCGGCGGGATCCGGCAGGGCGGCGCGGTCCACCTTGCCGTTCGCGCT CAGCGGCAGCGCCGGGAGGACGACGACCTCCGCGGGGATCATGTACTCCG GCAGCTTCTTCCGGACGAAGTCGCGGAGCGCGGCGCCATCGCCGTCGGCG CCGACGACGTACGCGACCAGGCGCTTCTCGCCCGACGGATCGGTCTTCGC CGCCACGACCGCCTGCTCGACCGAGGGGTGCTGCGCGAGGGCGGCCTCGA 5 TCTCGCCGAGCTCGATGCGGAAGCCGCGGATCTTCACCTGATGGTCGGTG CGCCCGAGCAGCTCGATGGTCCCGTCGGCGAAGTAGCGGCCCAGGTCGCC TGTCCTGTACAGCCGCTCGCCGGTCGTGGGGTGCTTCAGGAACCGCTCCC GGGTCCGCGCCTCGTCGCGCCAGTATCCGAGCGCGACGCCGATCCCGCCG ATGTGGATCTCGCCGGGGACCCCGATCGGACACGGCTCCAGCCCCTCGTC D GAGCACGTAGGTGTGCTGGTTCGCGAGCGGGCGGCCGTAGGGGATGCTGC GCCACGCCGGGTCGACGTCCGCGATCGGGTGGGCGATCGACCAGATCGAC GCCTCGGTCGCGCCGCCGAGGCTCACGACGCGGGGCGCGCGGCAGGCCGC GCGGATGCGATCGGGGAGCTTCAGCGGGATCCAGTCGCCGCTCATCATGA CGAGGCGGAGCGACGACAGCGCCGGGTCGCCCGCGCCGGGGGACGCGTCC ATGAGCATCTCCATCAGCGCCGGGACCGAGTTCCACACGGTCACCCGCTC GCGCTCCACGAGCTCGCGCCAGTGCCCCGGATCCGAGGCGCGGGTACGGT CGGGGATCACGACGGCGCCTCCGGCGGCGAGCGTCCCGAACACGTCGTAG ACCGACAGGTCGAAGCTCAGCGA:GAGAGCGCGAGCACCCGGTCCTCCGG GCCGACGTCGAAGCGGCGGTTGATGTCGAGGACCGTGTTCACCGCGCCGC D GGTGGTCGATCATCACGCCCTTGGGCAGCCCCGTGGACCCGGACGTGTAG WO 00/22139 PCT/US99/23535 199 ATCACGTAGGCCAGGTCGTCCGTGCTTCCGCCGGGCGGCCGGCGCGCGAC GGGCTGCTCGCGCCACCGCTCGTCCGCGTCGACGGCGAGGCGCTCGATGC CCGCGGGCCAGGCGATCGTCCCGTCGACCGCCGACTGCGTGAGGACGAGG CGGACCTCGGCGTGCTCCAGGAGGTGCCTGAGGCGCTCCTCGGGGAGGCG 5 AGGGTCCAGGGGCAGGTAGGCGGCGCCGGCGCGCAGCACGCCGAGCACGG CGGCCACCTGCTCCCAGCCCTTCTCCATGACCACGGCGACGAGCGCGTTC GCGGTCGCTCCGGAGCGCGAGGCCGCCGCGGCGATCGCCTCGGCGCGCCG GGCGAGCTCCCCGTAGGTGAGGCGCCGCTCGGCGTCGACGACCGCGCACG CGTCGGGCTGCTCGACGGCGCGCTCMSAAGAACGGCTCCTCCAGCCGGAGG o TGATCCGGGGTTGCGACCGCGGTGTCGTTCCACGCGACGAGGGCGCGCTC GC-GGTCTTCCGGCGCGACGGAGAG--CGCGCGGACGCGCTGCGCGGGGTCCT GAGTGGCGCGCGAGAGCACGCTCTGCATCGTGGCGAGCATCCGGTCGATG GTCGCCGCGTCGAAGAGGTCGACGTTGTACTGGAGCGAGATCACGTCGCG CCCGCCGCGCGGCTCGACGCTGAAGCGCAGGTCGAAGCGCGTGGCCTCGA 5 CCGGGAGATCGAGCGGCTCGATCCGCACCTCGCCGAGCTCGAGCGCCTCG GTTGGGGCGTTCTGCACGACGAGCATGACCTGGAACAGCGGCGAGCGGCT CAGGTCGCGGCGGGGGTTGACCGCCTCGACCACCTTCTCGAACGGGGCGT CCTGGTGCTCGAACGCCTCGAGCGCGACCTTCCGCGCCCGCGAGAGGAGC TCCTCGAAGGTCGGGTCGCCGCCGAGGTCGAGGCGCATGACGATCGTGTT 0 CACGAAGAAGCCGACGAGGGGCTC-GAGCTCGGGGCGAGGCCCGTTGGCGA CC GCGGTCCCGATGGCGAGGTCGTC-CTGGCCCGAGCTGCGCCGGAGGAGC ACGCCGAGGGCGGCGAGCAGGACCATGAAGCGGGTGGCGCCGCGGCTCCG GGCGAGCTCGTCGAGCTGCGCCACGAGGCGCGCGTCGAGCGGGAGGACCC GCTCCGCGCCGCGGAACGTCTGGACGGGCGGCCGCGGTCGATCGGTCTGG 5 AGCJ''-TCCAGGACCGGCAGCCCGCGGAGGGTCGCTGTCCAGTGAGCGAGCTT GTj'-CGGCGAGCCGCTTCCCCGCGAGG- TGGCGGCGCTGCCACACCGCGAT CGACGTACTGGAGCGGCAGCTCGGG "CATGTCCGCGGGCCCGCCGCCCCGC GC -GCGCCGGTAGAGCTCCGCGAGATCGCGGACGAGGGGTTGGAAGGACCA GGCGTCCGTGACGATGTGGTGCGTGGACAGGACCAGGACGCAGACGTCGT 0 GG"'TCGAGGCGGAACAGCCTGGCC-CGGAACACGGGCCCGCGCGCGAGGTCG WO 00/22139 PCT/US99/23535 200 AACCCCGTGGCCTGCTCGCGCGACGCCCAGGCGCGCGCCGCGGCCTCCGC CTCGTCCGGGGGCGTGCCGCGGAGGTCGACCACCTCCGCGGGGGCCGCCT CGGGCTCGCAGATCTTCTGCGCCGGCGTGGGGCTCGCGACGAACACCGTG CGCAGGCTCCAGTGCCGCCGGACGAGCGCGGCGAGCGCGGAGGACAGCGC GTCGACGTCGACGAGGTTCCGCAGGCGGACCGCCTGCACCACGTTGTAGG CGGTCCCGCCGGGGAGCAGCTGCTCGAGGACCCACAGGCGCTCTTGCTCG TACGAGAGCGGATACGGCTCGTCCGCCGGCGCGCGGCCCAGCGAGGGCGC GATCTCGCTGGCGGGCACCGTCGCTGCGGCGGCGGTGGTCGAGGCGGCGC CGGAGGAGAGGCGATCGGCGAGCTGGTGGAGGGTTGGGTGCTCGAAGAGC GTGCGGAGGGTGGTGCGGATGCCGAGGGAGGACTCGATGCGTCCGAGGAC CTGCATGGCGAGCAGGGAGTGGCCGCCGAGGTCGAAGAAGCTGTCGTGTC GTCCGACGCGGTCGAGGTGGAGGACGGATTGCCAGATGTGCGCGAGCTCC CGCTCGAGCTCGCCCGAAGGGGGCTCGTAGTCGGCGTGCGCGGCGGGTGG CGCAGGGAGGAGCTTCTTGTCGACCTTGCCCGAGAGGGACATGGGCAAGG CGGGGAGCAGGACGAAGTGGGCGGGCACCAAGGCGTCGGGCACCAGGCGG GCCATGCCCTCGCGCAGGTCGCGCTCGGAGGGCGGGTCGGCGCCCGGCAC GACATAGGCAATCAGGCGCGCGGCGCTGCCTTGGCCGTGGAGGACGACGA CGCCCTCGCGGACGGCGGGCAAGCGTCGCAGGGCGGATTCGACCTCGCCG AGCTCGACACGGCGACCGCGGAGCTTGACCTGCTCGTCGCGGCGTCCGGC GAAGGCGAGCTGTCCGTCGGGGCGCCAGCGCACCAGGTCGCCGGTGCGGT AGAGGCGTGCGCCGGGCTGGCCGAAGGGATCGGGCAGGAAGCGCTCTGCG GTCAGGTCCGTGCGTGTGTAGCCCTGGGCGAGGCACGCTCCGCCGATGTA CAGCTCGCCGAGGACGCCGGGCGGGACGGGCTGCATGTGCGGGTCGAGGA CGTAGACGAGGGCGCTGTCGATGGGTCGGCCGAGCGGGGGCTCGTCGCCG AGGTCGGCGACCTCGGCGACGGTGGTGATGACGGTGGCCTCGGTGGGGCC GTACATGTTGAAGAGGCGGAAAGGGAGCGGTCGCCGGAGCGGATGGAGCT TGTCGCCGCCGACGGTCATCGCGCGCAGGGCGATGCCGGTCCAGTCTTGC TCGAAGCACGCCTCGGCCAGGGGCGTGGGCATGAACGAGAGCGTGGCCCG CTGAGCGACAAGCCAGGAGACGAGCGCTGTGGGAGAGCGGAGCGCGTCGT CGTCGGCGAGGAGGAGTGCAGCGCCGCAGGCGAGCGGCGTCCAGATCTCG WO 00/22139 PCT/US99/23535 201 TAGACGGAGGCGTCGAAGCCGCTGGAGGCCAGCTGAGTCCAGCGATCGCG GGGTGAGAGCGCGAGCAGGTGCTGGAAGAAGGAGACGAGCCTTGAAAGGC TCGCATGGCGCACACAGACGCCCTTCGGCGTGCCGGAAGAGCCGGAGGTG AAGAGGACATAGGCCAGGTCGTCGGGCCTGGAGACGAGAGGAATGTGGGT GCTGGGCGCGCACGCCCCGTCCTGGACGAGGTGGACGGGGCAGGGGGCGG CGGTGAGCTTGTGGCTGGCCTGGCTGCTGGTGAGCACGAGCGCGGCGCGG CAGTCGGCGAGCATCTCGGCCAGGCGCGCCGGGGGGTTGGCGGGGTCGAG CGAGGCATAGGCGGCGCCTGCCTTGAGGACGGCGAGCTGGGCGGCGACCA TGCGGGGCGAGCGCTCGATGCAGACGCCGACGACGCTGCCGGGGCCGACG CCGCGGTCGCGCAGCCACAGGGCGAGCTCGGTGGACCAGGTGCTGAGCTC TGCGTAGGTGAAGCGCTGGTGTCCGAACTCGAGCGCCGTGGCGTCCGGCT GTCGAGCGGCGTGGGCCTCGAAGAGCGCATGGACGCAGGCGGGGGCCGGG GCGGAGGCGGCCTGTCGTGCGGCGGCAGCGCCGCTCCAGTCGTCGAGGAG CAATGCGCGCTCGGCGTCGGAGAGCATCCGGAGCTCGGAGAGCGGTCGAC CGGGGTGCTCGACGGCGCTTTCGAGCAGGAGCACGAAGTGGCGCGCCATC CGCTCGATGGTGGCGGGGTCGAAGAGCTGCTGGTCGTACTCGAAGCGCAG GGCGATGCCGGAGTCGAGCTCTGCGGCGAACAAGGCGAGATCGAACTCGG CCGCTGCCTGCTCGTCGGCGAGCGTGGTGAGCTCGAGCTCTCCCTGCGCG ATCCGCACGTCCTCCGCGCCGGTGGTGAGCGCGGCGAGGCGGGGATCCAG CGACGGCAGAGCGCCCTGGAAGGCGAAGGCGACGTCGAAGAGCGCGCCGC CTCGCCGGGCCGCGCCCCGGGGCTCTGCGAGCAGGTGCTGGAGGGCGCTG TCGCCGTGGGCCAGCCCGTCGAGGAACGCGTCGCGCACGCGGGCGACGAG CGCGTCGAAGGACGCGGCCCCGCGCAGCGCCACGCGCACGGGGAGCATCT GGACGAAATAGCCGAAAGCCCGAGTGCTCTCGTCGTCGTTCCGCCCCGCC GAGGGGACGCCCACGACAAGGTCGTTCTGCCCGCTCGCGCGATGGAGCAA GACGGTGAGCGCCGACAGCAGGACCGAGAAGAGCGTGGTCCCGCGCTCGC GCGCGAGGCGCGCCAGCGCTCCGGTCAGGGGCTTTGGCAGCGTGATCGCG TGAGCGCGACCGCGGCGAGGGCTCGCGTCGTGGCGGGCCCGGTCGCGGGG AAGGTCGATGGCGGTCGTCGCGCCGTCGAGCGCCTTGCGCCAGTATTCTG CTCCGCCGGCCGCCTCCCGCGGCGAGGGACAGCTCACGCCGGCGGCGAAG WO 00/22139 PCT/US99/23535 202 AAGCTCGACGGCGGCGGCAGCTGCGG GGGCCGGCCCGCGCGCAGCGCCGA GTACAGCTCCCCCAGCTCGCGAAC -GAGCAGCGCGAACGACCAGTAGTCGA CCACGAGGTGGTGAACGACCACCGTGAGCAGCGGCGGCTGCCCCTCTCCG CGCCGCCAGACATGCACCCGGAGCAGCGGTCCGCGCTCCAGGTCGJACGC 5 GCGGCGGCGCACCTCGTCCGCGCGGGCGACGATCTCGCGCTCGTCCAGCG CCATCGCCGGCTCTTCGGCCCATTCCAGGGCGACATGGCGGTGGACCTGC TGCAGCGGATGGCCGTCGCGCGTGAGGAACGTCGTGCGGAGCGCCTCGTG CCGCTCGACGAGGCCCTCGAACGCGCGGCGCAGCGCGGCCACGTCGACGC CGGCACCGAGCCGGACCGTCCTGCCCAGGTTGTAGAGCGCGCCGTCGGCC 0 GACTTCTGGCACTCCAGCCACATC -GCCCGCTGCCCCTCGGTCAGCGCAAA CGGCTCTTCCGGCGTCGCCACCCGC GGCGACGAGGGGCCGTCCGGACGGG TGAGCCCTLCGCTCCAGGGCCGTCGC(-TGCGGCGGCGGAGGTCGAGGCGGCG CCGGAGGAGAGATGACTGGCGAGCTGCGCGAGGGTTGGGTGCTCGAAGAG CGTGCGGAGGGTGGTGCGGATGCCGAGGGAGGACTCGATGCGTCCGAGGA 5 CCTGCATGGCGAGCAGGGAGTGGCCGCCGAGGTCGAAGAAGCTGTCGTGT CGTCCGACGCGGTCGAGGTGGAGGACGGATTGCCAGATGTGGGCGAGCTC GAGCTCGAGCTCGCCCGAGGGc3GGCTCGTAGTCGGCGTGCGCGGCGGGGG GCGCAGGGAGGAGCTTCTTGTCGAC CTTGCCCGAGAGGGACATGGGCAAG GCGGGGAGCAGGACGAAGTGGGCGGGCACCAGGGCGTCGGGCAC CAGGCG 0 GGCCATGC -CTTCGCGCAGGTCGCGCTCGGAGGGCGGGTGGGCGTCTGGCA CGACATGGGCAATCAGGTGCGCG gCGCTGCCTTGGCCGTGGAGGACGACG ATGCCCTCGCGGACGCCGGGCAAGCGTCGCAGGACGGATTCGACCTCGCC GAGCTCGACGCGGCGACCGCGGAGC-TTGACCTGCTCGTCGCGGCGCCCCG CGAAGGCGAGCTGTCCGTCGGGGCG--CCAGCGCACCAGGTCGCCGGTGCGG 5 TAGAGGCGTGCGCCGGGCTGGCCGAAGGGATCGGGCAGGAAGCGCTCTGC GGTCAGGTCCGTGCGTGTGTAG' -CC'TGGGCGAGGCACGCTCCGCCGATGT ACAGCTCG"CCGAGGGCGCCGGGCGG--'-GACGGGCTGCATGTGCGGGTCGAGG ACGTAGAC-GAGGGCGCTGTCGACGG7--GTCGGCCGAGCGGGGGCTCGGCGCC GAGGTCCf-CGATCTCGGCGACCGT-GGTGATGACGGTGGCCTCGGTGGGCC 0 CGTACATG-TTGAAGAGGCGGAAAG--GGAGCGGGCGCCGGAGCGGATGGAGC WO 00/22139 PCT/US99/23535 203 TTGTCGCCGCCGACGGTCATCGCGCGCAGGGCGGAGCCGGTCCAGTCTTG CTCGAAGCACGCCTCGGCCAGGGGCGTGGGCATGAATGAGAGTGTGGCCC GCTGAGCGACAAGCCATGAGACGAGCGCCGTGGGAGAGCGGAGCGCGTCG TCGTCGGCGAGGAGGAGGGCAGCGCCGCAGGCGAGCGGCGTCCAGATCTC 5 GTAGACGGAGGCGTCGAAGCCGCTGGAGGCAACCTGAGTCCAGCGGTCGC TGGGCGAGAGATCGAGTCGGAGGTGGAGGAAGGAGACGAGCCTTGAAAGG CTCGCATGGCGCACACAGACGCCCTTGGGGGTGCCGGTGGAGCCGGAGGT GAAGAGGACATAGGCCAGGTCGTCGGGCCTGGAGACGAGAGGAATGTGGG TGCTGGGCGCGCACGCCCCGTCCTGGACGAGGTGGACGGGGCAGGGGGCG 0 GCGGTGAGCTTGTGGCTGGCCTGGCTGCTGGTGAGCGCGAGCGAGGCGCG GCAGTCGGCGAGCATCTCGGCCAGGCGTGCCGGGGGGTTGGCGGGGTCGA GCGAGGCATAGGCGGCGCCTGCCTTGAGGACGGCGAGCTGGGCGGCGACC ATGCGGGGCGAGCGCTCGATGCAGACGCCGACGACGCTGCCGGGGCCGAC GCCGCGGTCGCGCAGCCACAGGGCGAGCTCGGTGGACCAGGTGCTGAGCT D GTGCGTAGGTGAAGCGCTGGTGGCCGAACTCGAGCGCGGTGGCGTCCGGC TGTCGAGCGGCGTGGGCCTCGAACAGCGCGTGGACGCAGGCGGGGGCCGG GGCGGAGGCGGCCTGTCGTGCGGCGGCAGCGCCGCTCCAGTCGTCGAGGA GCAATGCGCGCTCGGCGTCGGAGAGCATCCGGAGCTCGGAGAGCGGTCGA CCGGGGTGCTCGACGGCGCTTTCGAGCAGGACCACGAAGTGGCGCGCCAT D CCGCTCGATGGTGGCGGGGTCGAAGAGCTGCTGGTCGTACTCGAAGCGCA GGGCGATGCCGGCGTCGAGCTCTGCGGCGAACAAGGCGAGATCGAACTCG GCCGCTGCCTGCTCGTCGGCGAGCGTGGTGAGCTCGAGCTCTCCCTGCGC GATCCGCACGTCCCCCACGCCGATCGCGAGGGCTGACAGGCGTGCATCCA GCGATGGCGGGGTGCTCTGGAAGGCGAAGGCGACGTCGAACAGCGCGTCT 5 CGCTGCGCCTCGCCCTGCGCTCGCGCGAGCAGGTGCCGGAGGGCGCTGTC GCCGTGGGCCAGCGCGTCGAGGAACGCATCTCGCACGCGGGCGACGAGCG CGTCGAAGGACGCGGCCCCGCGCAGCGCCACGCGCACGGGGAGCATCTGG ACGAAGTAGCCAAAGGCCCTGGCGCTCTCGTCGTCGTGCCGCCCCGCCGA GGGGACGCCCACGACAAGGTCGCTCTGTCCGCTGGCGCGATGGAGCAAGA D CGGTGAGCGCCGACAGCAGGACCGAGAAGAGCGTGGTCCCGCGCTCGCGC WO 00/22139 PCTIUS99/23535 204 GCGAGGCGCGCCAGCGCTCCGGTCAGGGGCTTTGGCAGCGTGATCGCGTG AGCGCGACCGCGGCGAGCGCCCGCGTCGTGGCGAGCCCGGTCGCGGGGGA GGTCGATGGCGGTCGTCGCGCCGTCGAGCGCCTTGCGCCAGTATTCTGCT CCGCCGGCCGCCTCCCGCGGCGAGGGACAGCTCACGCCGGCGGCGAAGAA GCTCGACGGCGGCGGCAGCTGCGGGGGCCGGCCCGCGCGCAGCGCCGAGT ACAGCTCCCCCAGCTCGCGAACGATCAGTGCGAACGACCAGTATTCGACC ACTACGTGGTGATCCACCACCGTCAGCACTCTGCGTTTAGTCCTTTCTCC TGTTCGGCCTATTAATTGCTACTATGGATCCACACTGCTCCGCCTCTTGT ATCTCCCTTATCTGCACTTGCTGCGCTTNACCTTTACGTTCCTCTCCCTG CTCTATACTATTTCTTCCCCCGCTTCTCGTCCTATTCTGCATTTGTCATA TCGTATCTTCATATACCTTTCTTTCGCTATCCTTACTGCTTCTCGACCTT ATGTGCGTCTGTCTTCCCTTTCTNTATTATTTCTCTGTCTCACCGCTCTN TGCTCTGTCGCTCCTATCACTAAATTATGTCTCTATCACTGCTACTATCT GAAGCTGATCTTCGAGATCTCGCTNGGTGTCACTCTTTATCTCATAGNCG CCTCTGTCTTCTTGTCTCCTTAAGNCTGATTTTCTCGCTCTATTCGTGAC TACTCTGCTGTCTCTCACATACGTGTTCTTGAATCGTATTCGCGTTCTCG CTACTGTGATATCCATTGCCGACCTCTACTGCTCNTCTNTATGCTATACT TCTTAGTCTCTTACTACGTTNGTCTGATATNTTGCTGACGACGTCATGTC ACGCTCGCAACTCTTCANTTCTATCGTATACGCTGATCATCATTTTCTGT GAGGCTGATGTACTATACGTAATTACCTGTATACGTCGTCTATCTACTCT CGTGTCTTCACTCTTTCTACTCC Seq ID No 91 (>Contigl2) CCCCCCGCCGTCCGCCGGTACGTCGCGGACCGCCGCCCCGAGCAGCTCCC CGCGCTCGCGCCGGAGGAGCGGGAGGCCGCGGCGCGCCGCCTGTCGGCCC TCGGCGCGGCGCCGCCGCAGGTCCGGCGCCGCGGGCTGACGCGGGCGCCG CTCTCGTACGGGCAGAGCCGCATCTACTTCCTCGAGCAGCTCTCGCCCGG CAAGCCGCTCTTCAACGTCCCGGGCGCGGTCCGGCTCCGGGGCCCGGTCG ACGTCGCCCGCCTCTCGGCAGCGTTCGGCGAGATCGTGCGGCGCCACGAC GCCCTCCGCACGTCGATCGCCAACGTCGACGGCGAGCTCCTGCAGATCGC WO 00/22139 PCT/US99/23535 205 GCAGCCGCACGCGGGCTTCGCGCTCGACGTGGTGACCTCGACGCCCGAGG AGGCGGCCGAGCTCGACCGGCGGCTG-CGCGCCGAGGCGTG GCGGCCCTTC GCGATCGGCGCGCCGCCGCTCCTGC GCGCCACGCTGTTCCGCCTCGCGGA GGACGAGCACGTGCTCCTCGTCACGATGCACCACGTGGTGTCGGACGACT 5GGTCGCTCGGCGTGATCCTCCGCGAGCTCCTCCCGCTGTACGCGGOCCGC TCGCTCCCGCCGCCGCGGCTCCAGG-:TCAGCGACTTCGCGGCGTGGCAGCG CGAGATGGTCGAGTCGGGGGCGCTCGACGGCCAGCGCGCGTACTGGCGAG AGCGCCTCCGGGGGCTGTCCCGGGCGAGCATCTCGGCCGGCGGCGGGGCG GAGGCGCCGAGCCACGACCCGTCCGGCGCCATCGAGGAGATCGCGCTCTC D GCCGGACAAGGCGGCGGCGCTCGAG-GCGCTCGCGCGGCGGGAGGGAGCGA CCCTGTTCATGGTGCTCCTCGCGCTC-CTCGACCTCGTGATCCATGCGCGG TCCGGCGCACTGGACATCGCCGTGGG--GACGCCCATCGCCACCGGAACCG CCCGGAGCTCGAGGACGTGGTCGG CTCTTGACGAAJCACGCTCGTGATCC GCGTCGATCTCGCGCGCGCCGGGGCGTTCCGCGACGTGCTCGCGCGGGCG )CGCGTCCAGGCGCTCGACGCCTTCG -CGAACCAGGACATCCCGTTCGATGT CGTCACCCAGGATCTGAAGCAGGAG7CGCGACCACGCGCAGCACCCGCTCT TCCGCGTCTGGCTGGCGCTCCAGACGCGCCGAJAGCCCGCGCTGGAGGTC CGCGGGCTCCGGGTCGAGCCCCTGCC-CCTCCGGCCCGAGCTCGTGCACTT CGAGGTCGCCCTCCTGCTCTGGCCGGCGGACGACGGATCGGTCGTGGGGC DACTTCGAGTTCCGGCGCGATCGCGTCGACGAGGGCGCGCGCAAGGAGATC GCGGCCGCATTCACGCACCTCGTCG,-'ACGCGGTGATCGCCCGGCCGGACGC GCCGGTGTCGACGCTCGTGGAGGGC,'GCCCGCGCCGAGGCCGCGCGAGCGC AGGCCGCGCTCGGCGAGGCGTTCGC-CAGGGCGGCGACGGCGCGCCTCGGC CAGCTGCGGCGTCGCTCGGCGGGCGl-ACCGGACGCCCCGCGAGTAGCGGTC DAGCCCTCGGCGGCGGCCAGGCGCACGCGGAAJCGGCGCAGGGTAGCCGTGG ACGCGCGGCATGGGc3TCGATCGCGCC-TGGGGACGCCGGCCCGCAGCAGCTG CTTGATGGCGAGCGAGATGTGCAGG-ATGGCCACGTACTTGCCGTGGCACG TATGGATCCCTGACTCCCAGAACA3,GTAGT~rTTCTGCTCGGCAGGCGCCCG GGCC "TGAACTGGTCCGGGGCGTCGATGTGCTCGTGGTCGTGCATCGCCGA DGGCGCTGCAGGCCATCACCAGCGCGC' CGGCGGGGACCTTCTCCTCGTGCC WO 00/22139 PCT/US99/23535 206 GCGTGCCACGCCCGACCGTGTAGTCGCGCACGCAGAGGCTCGTGACGCCG GTCGACGGGGGACGGAAGCGCAGCGCCTCCAGCACATAGCCGGTGATGGC GGCGTCGTCCTCGACGTTCACCACGTTGAGCGCGTCGCGCAGGACGCGCG GGCGCTTCATCAGCTCGACCAGGGCGTTGACGATCGCGCCGCCGCTGAGA 5 TCCACGCAGCCCATGAGCAGCCCCAGGATCACGTCGCGGATCCCCTCGTC GCTCTCGTAGGTCTCGGGGACCGACTGCATGACCAGGTAGCGGTCCAGCA CCGAGGGTTGCTCTGGCGGGGGCGACTTGGCCAGCTGCTTCTTCCGCGCG GCGACGATCGCGTCGATCATCGGCAGCGCCTCCTGACGAGCGGCCCTCGC CGCCGCCACGGCCGTCGGGTCGTTGGTCGGGTTGAGGAAGATCTCGTTGA D ACAGCGCGTGGGTCCACGCCACCACCTTCTCGGTCGGGATCTCGCCGACG CCGAGGTACCGGGCCATCGCGCCGGCCGGCACCCTGAGCGCGTAGTCACC GGTGAGATCGAACGGCTTGTCGACGCCGACCTTGGCGAGCAGCCGGTTCG CCTCGTCCACGACGATCTGACGGTAGCGGGGCAGATCGGCGCGCGGGAAC GCGAGGCGCAGGAGCGACTTCTCGTGCTCGTACTTGGGCGAGTCGTTCAT 5 CGCCAGGATGTTCTGGCCCACGTTCTCGACCAGCTTGGGCGCGATGTTGT CGACCGAGAAGACGTCGTTGGCGTTGAGGACCTCGACGACGTCGTTGTAC CGGGTCACGAGCGTGATGGCCGGGATGGAGAAGATGGGCTTCTCGCGCCG CAGCTGGCTGAGGAACGGGAGCGGCTCCTCCCTCAGCCACTTGAACACCA TGCCGGCCTCGATCTGCTTCCGCTTGACCGGATCGTTCTCGTGCGCCAGC J GCGCTGTGGAGGGCCTGCAGGTAATCGAACGGCGGCGCCTTGGCAGCGTC CGCTCGTCCCTCTTCTTCGATGTGAATGCTCATGGGGAGAATTCCTTTCT CGCATGCCGATCAGATCGCGACGCTCTGGGGGACCATCGACGGGAGCAGG TACAGGTACGGCTGCTCGCGGGCGCGGTTGCGCTCGGTGATCTCCCGCTC GATGTGCGCCAGGCGCTCGCGGTAGCGAGCAAACGCCTGCTTCGCCGCCG 5 GATCTTGCAACAGGCACTTCATCGTCATCAGGCTCTCGCTGGTCAGCGGC GGGCCCATGCTGAGCGAGCGGCTGAGCACCATCTGGCGGATGCTCTGCGC GCGCCCCGGGAGGCGCTCCAGCGGCTTGAACTGCCGCTTCTCGCTTCCGT TCAGGACATCGCCGTAGGAGCGGTAGGTGGCAAACTGAGCGTTCGGGATC CAGGTGTAATAGTCCGTCTGCCCGAAGTTCACGGCGGCGTGATATGCGGT D CGCCGTGAAGATGATGTTGGTGACGATCGCGATCAGGTCGTCGAGGCTCG WO 00/22139 PCTIUS99/23535 207 TGAGCTTCTCGAGCTGATCGGCTCGCTCCGGCGGGAGGAGGCTATCCATG CCGCCGAGCTGGGGGGACACGAGCTCGTGGATCCACCGCTGCAGGCTGGC GTCGCTCGACAGAGACCCCGGCGTCGGGTAGGCGATCTTCAGCACCTGTC CGACGTACTCCTGGATCGCGTCCCAGTGCAGCAGCGCGTCGTCGCGGTAG 5 TGATAGCCGACCAGGTCGCGGACGTCGCGCGCCGACAGGTCGCGGGGGAG CGCGCTCTCGTAGAACCGCCACGGCTTGCCGCCGTACCCTTTGATGCCCT TGCCGGTGTAGGCGCGCGTCAAGAGCTCGAACGAGCCCATGGTGGCCACC GAGCTCGTGATGTCGAAGAAGCGCCCTCGCCCGAGGAAGCGCCGGCGAGC CAGCTCGTTGATGGCCAGGGTGTTGAAGAAATGCGGCCTGAGCAGCTGGT 0 GGAGCGGATGCGTCGCGGGCAGGTTGCGGTAGGTGCTCACCGCGAACGGC TCCACGATCAGGTGCGCGTACAGCAGGTGGGTCACCTGGCCCTGGTAGAT GGCGTCGGCGCTCGCGACGGCGATCTTCGCCGTGAGCCAGTCGTCCGACG GACCCGAAGGGGTGAAGATCTTGTCGGGATGCGCCCCTTTCCCGGGGCGC GAGTGCACCAGCCTGATGGCCACGGGCAAGAGCTCACCGGCCGCGGTCTG 5 GTGCAGCATGCACGTCGGCGCCAGCGGGTACTTGCCCAGCTCTTCCTGCA CGTCGGTGTCGACGATGTCCTTGAAGATGCGGTAGTCGAGGAAGTAGAGC TGCCCGCCCTCGCGCACCTCCTCCAGCGTGCGACCGTCGGCGATCGCGAT CGGCTTGGGCTCGGCGCCGCTCACGAAATCGGCGAGATCGGCCGGGGTCG CGCGGCGGATGTGCGCCGGGTTGATCCCCACGAGGCGCTGCCGCCCGAAC 0 TCGGCGTCCTCGGCCCAGCGCGTCGCCACGAGGGGCTTGCGGATGAAGGT CCACGGCTTGAAGAACTCCTCGAACTGATCGAAGCTCTCCCAGTTGTCGA TGGACTCGAAGATGGCGCCCAGCCCGAGGTCGGACGTGGCCCTGAGGACG AACTTCCCCTCGCGATAGCGCTTGTACCCGTACTCGAACAGGTGAAGCGC CTGCGCGATTTGCAGTCCGGCAGTGTCCTTCCACTTGCCGAGGTTGAGCG 5 CCAAGATCTTCTTGATCGGAAAGCCTTCCCCCGGCGGTACGGAATCGCTG CCCGCCGGCAGGTTGGACCCGAAATTGCGCCAGTTCGGTGTCGAGCTGGG CTCCCTCATGCTCGTGCTCGCTTCTCCGTCTCAGACGGACGGTGGATTGG GTGGTTCACGTCAAACATCGCTCTCGCGTCGCAGCGGTCCGAGCGCGCGC CGGAATGGTTCCGTCTCAGTCGCAACAGGACTCAGTACATCCAGCGCCGC 0 CCCCCGTCCTCGACCTGCCCCCGCAGCCGATCGCGCCGCCCTTCATCGTG WO 00/22139 PCT/US99/23535 208 GAATCGACAGGTGCGATTCCACGAAAAGCCGCCGCGCCGAGTTGCACGCG ACCGATGCTCACGCGTGCATTGTTGAGGCTGCTAGAAAACCGTGGAGCGT TCACGCATGTCAAGCCATTTTGTTCGGCGCCGCGGCGAGCGGCCGGATGC CGCGCGCCCCCGCGCCGGGCGTGTTCGCTCCCGACGTACCGCTACCTCGA 5 CGACGTATGGCTTGAAGGGCAACCGCGCAAGTCGTCCGATTCGTGCTCGT ATCCTGCTCCTTCCAGCAGGATTTCCCCGCCGCCAGCGGCACAAAGGTGC CAGGGCGAGCAGAAAGAGCGCTGCCCGCCCCTCCCCGGCCGCGCTCGCCT CGATCAGCGCGCGCTCGTCGTCGGTGCCTGAGACGTTCGACGGACGTCAG TTAGTTAGCCTAGCTAACTTCAACACTGATGCGACTGATCGGGCCGACGC 0 AACCGACGCAACCGACGCAACCGACGCAACCGACGCGACCGACGCAATCG ACGCAACCGACGTGACGGACGCTGGCGACTCGAAGAAAACCACGGACGCA CTCCACGTCATCGACGTCATCGACGTCATCGATGCGCTCGATGCAATCCA TGCACTTGACGCGATCGGTGCGAGCAGGCGACGAGGTCCTCTCGTGAAAC ACCGAACCGAGTGCCGGTAGCGGGCGCGCCGCAGTGTATGCTAGGCTCGG 5 CCCTCTTGTCGAGGCCGCGCGCTCGGCGGTCGAGCGTGGGCTCGGGTGCC GCGGTATCCGGCTGAACCAAGGAGGAGCGAGCCATGCAGGCAGATGACGA CGCGACGATCTACAAGGTGGTGGTGAACCACGAGGAGCAATACTCCATCT GGCCGGCGGACCGAGAGAACCCGCTCGGCTGGACGGAGGCCGGCAAGACG GGCAACAAGGCGGAGTGTCTGGCGTACATCCAGGAGGTCTGGACGGACAT 0 GCGCCCGCTCAGCCTCCGGAAGAAGATGGCCGAGAGCCCCTGAATCGCGG CCCGCCCGAGCGCCCGTCGCGAGCGGCCGGGCGGCGGGCTCAGCCGTGTC ATCGTCGCGCTCGACCGGCCGCGTCCCGCGGGATCGCGCGAGCCCGGCGG GGTCGTGCGCGCCGGCGCTTGTGCCGGGGCCCCCGCTCTCGTACGCCTCC GTCATGCCGCCCCTCGATCTGCACGTCGCCTTGTTCGGCGCCTCCGGCGC D CGGCAAGACGGTCCTCCTGGCAGCCTTCTACCGGGCGCAGACCCAGCCCT CGTTCCAGCAGGAGTACGCGTACAAGATCCAGGCGGTCAACAAGGCGCAG GGCAACCAGCTCCTCGGCCGGTTCTATCGCCTCGAAGAGGGCAGATTCCC GGACGGCAGCACGCGCTTCGACGAGTACGAGTTCGACTTCTTCCCGAGAG ATCTGCCCGAGCCGGCGGTCCGCATCCACTGGTACGACTACCCGGGACGC D TGGTGGGAGGACGAGCCGGTCGACGCGGACGAGCGGGAGGCGATGCGCCA WO 00/22139 PCT/US99/23535 209 GGGCCTCATCCGGCTCGGGATGAGCCAGGTGGGCATCCTCCTCGCGGACG GCGCGAAGTACCGGGCCGAGGGCAC-CGGGTACATCCGGTG OCTGTTCGAG CACTTCGCCGACGAGTGCGACCGGC TGCGCCGGGCCAGCGCCGCCACGGG CGACGAGGTGAGCTTCCCGCGGGAGTGGATCCTCGCCCTCAGCAAGGCCG 5ATCTCTGCCCGCCGGACTACAGCGCG- -CGGGACTTCGAGCGCGAGGTCTGC CGGGACGCCGACGATCAGCTGGCGAAGCTCTGCTCGGTGCTCCGCGCCGA GCACGCGTTCGGCCACCGCTTCATGC-TGCTCTCGTCGGTCGCCGCCCCGG CCGGCGCGCAGGTCGATCCGAGGAC CTCGCTCGGCGTGCGCACCCTCGCC CCCGCGATCCTGGTGAGCACGGTCG--AGGGCGCGGTGCGCGAGGCGCAGGC D GGCGAGAAAGGAGAAGTCGGCCGGAG- -AGACGTTCTTCCAGGGGCTCCGCG ATCTCGTGCAGTTCGTCGACTCCCT-CGACGACTTCCTGCCGAAGCGATAC CAGATCGTGAGCAAGATCCTGCGG-TTCATCTCGATCAAGGACTTCGCGAC CACCCGGCTCGACCGGCTCAAGAAGATGCGCGAGGACGCGATCCGGAAGG GCGACACCTTCACGGCGGTCCTGACC-GCGATGGTCGCGGCCCTGCGCGAC DGACGAGGGCGCCCGCGCCTACCACCAGAACCAGTGAGGTCGTCATGCCCG CGCCAGCGCCCCTCGTCGAGACATC GCGCCTCCTCTGGAGGACGCGCGGC GAGCACTGGGATTACGAGTTCATCTGTGTCCCCGAGATCCCGGCGCTGCC CGCCTGGCTCTCGACGCTCGAGGCGATGCTCGCCGACGCCGACGCCGGCG CCGGGGAGCTCCGCTATGGCCTGCT-CGAGATCGACGATCGCGGGCAGAGG DGCGCCGCGCGCCTATCCCTACGTGr'-C-CGTGAGGTTCCTCGATCCGGCGCG GAGGGACTGGACCGGACGGCAGGTCCAGCACTTCGCGGCCTGGTTCCCGC CGGTCCCGCCCGAGGCGGTCGCGGAGTTGCCAGAAGCGGTCCCCGCCGAC TGGCACCTTCGCGTGCTCGACGGC-CTCGCGGGGACGTACGGCTCCGGCGA GGTGTTCGGGCTCCCCGAGGCGACG ATCCGCGCCTGGAAGCGGAGCCACG DACGAGAGCCGGGCCGCGCGCGCGA-TGGCGATCGTCAAGGCGACGCCGCCG GTTTCGCTGGGCGGCGGCGAGGCG-CGCCGTCGCGGTGGACGCGGGTGCC GACATTA AA AA A AAAGCCGCCGGAG:CCGCCGGCCGCGGCGGGCCTCCTCT CGGTGGGCGCGGTCCCTAGCGGC CAGGGCCGGCGATTCGGCTGCTTCGCG ATCGGCGCCATGATGCTCGCCGCCT-TCTGTCGACTGATGCTCGCTTGCGG TGTGCGCCTCCTCGGCGCCTGACCGCTGCGCCGCGCAGGCCATCCGACGG WO 00/22139 PCT/US99/23535 210 GGGGTCGGCCCGGCCAGCGCCCGCCGGGCGACACCAGGGCATCGGCCCTC CGCTCGGGGCATCGATTGAGCTCTCCGAGCGGCGGTCCGTCGTCAATCGC CGCAGAGCTCCCACCGGGCGGAGCAGCTCTGGCCGGTGACCGCATAGGGG TTCGTCGGGCAGGTCCACCACTCGCCCTGGAAAGGACGCGGGTTGCAGTG 5 CGGGAGGCACTCCACCCACCCCGACGAGCACGAGTTCCCTACCGAGACGG TCGGCTGAGCCGCGCAGAACCAGCGTTTTCCTGCGAACCAGCCGGGATTG CACACATCGGGCGCCCCGCCGACGGGCGGATACACCGTGGCGACCGCCTG GATGTCCACGGCGTCGAGGGTCTCGCTCCCGAAGCGCACGCCGTCCTGAT CCGAACACCCACTCCAGTAGGTCATGATGGAGTCGTAGTCGTAGAAACCA 0 GGGTTCACGACGATGTACCGCCGGCTCGAGGGCCACCCGCTGGCGACGTC GCTCGCGGGGAGCGGCTCTCGTTGGCTGCAGGCGCTCGGGACCAACGGGT GATGCCACTCATGCATGAAGCCGATCGCATGACCCATCTCGTGGATCGCG TACTGCTCCACGCAGTCGAAGCTGTATTCGACCCGGGCTGTCTGCCAGTT GTACTTGATGCAACGGTTGAAGTCGGCGCCCCAGGGCTTGAACTGGACCG 5 AGCCGCCCTTGTTGTAAACGCCGATCGAGTCCGATTGGTTGGGCGCGTCG GGGTGGATCCTGACGCCGACGTAGGTCATGCGAGTGGCCGGCAGGAGCGA ATCGCAGCTCTCCCAGCCGGTGAAGCGAACCGAGCTCCAGCGTTCCCAGC TGCCCTGGAGCGCGGTGCGCACGCGCGTGATGACGTCCGCGAGCGAGGGG TTGGGCGCATGGATCAGCCCGCCCGCGGCGCCGTCGACCCTCTGCTCCGC 0 CGAGCTCGTGGGGTCGATGCAGACCGGGATCCGGACATGGCCGTCAGCGT CCTCAGGCCAGCGACTCGCGCTGTCGAAGACGCTCGCCTCGGCGGACCGC GGCGCGGCGGAGACGGTCAGCGCGGCGCCCAGCGCTGCGAGGAGCAGCGG ACCGAGCGAAGAGCGAAACCGCACATGTCGTTCAGGGCCCCGCGTCGTGC GGTGCACCGAGACAATCTCGAGCGGGCTCATGGACGCAAACGCGTTGCGA 5 TGGCCTTGCAGCATGTTCTTCTCCAATCGACGAGGGTTGTTCTGCTGAAC GCGGCTCCAGCGTGGAGCTCGACGCGGTTCACCGGCTTCACGCCGGGGCC GTGGACGAGACCCGAGCACGGGGGAGGTCGCAGCCGCACCGGCTCGCGGC GC-CCTCCACCCTGCACCTACGACGAGCCTGCCGCTCGGTTTCGCGGAAAAT GCCACCCCGCTGCCCAGCGGGCGAAGCGCGGACGAGGCGCTCGTCCCCAC 0 GGTAGCGCCGGTGCCGCTGCATCCACCGCGCTCCTCCATGGGTCGCTGCC WO 00/22139 PCT/US99/23535 211 CGCGGGTCGTCGAGGAGACGGACCCGGGGCGCGGATCCCTGGCTCGGCGT CGCATAGCTCGTAGGGGCGGCCTTGAGCCGGCGGTACGAGCGGCGCAGTT CAGCAGCCGACCACGTGGACGCGGCGCGCTCCGAGCTGCGCCGAGGAACC CTTCAAATATTCAGATGGAATTCACAGGGTGGCTGAGAGACGGGGAGTAA GATCTCAGAGATCTCCCTGCCTACCCGCATCCCTGTTCAATTTTCCGCCC ACAACGCGAACGGATGAGGAAATATCAGCCCGCGATCCCGACGGCCGACA GCATCAAAGGCCGCTCGAATCCAGGGGATTCGAGCGGCCTCGGTCGCGCG GACCCCCGCCGCGAGCCGCTTTGTCACCACTTCACCACTTCAGAGCTTCG ATCATCTTCTCACCATAACGCGTGCCCATGATAACAACGGACGCATGATC GAAGTGGTACTGATCCATGACGTTGGTCCCCTGCTGGCTGACCCAGTACC CCATAGGCAGCATGTCGGCCGCTTGGTGCACGAGGTTGTTATGACCGCCG CAGCACCCGCCCGCGGGGAGCTCTCCGAGAATGAAGGGAACGTCGTAGTC GACCCCCCAGGCTGCTTTCACCTCGTTATAGAGCTGAACGACCTTGCCGG GCCACGAGCTCTGGCCGTTGTCGGACTCACCCTGGTGGAAGATGATGCCC GCGAAGCGCGCGTTCTCGGCCGTCTTCGCTTTGGCGATCTTGTTCAAGAT CATCTGGTGATGCGAGCCACCAGTGATGAACGTGTTGATCGACTCGCCGC TCTCAGCGGTAGCGACCAACCCGATCGTATCCCCCTCAGGCAGCTTTCCG AGCAGGGTCTTGCCGAACCAGATGCCCGGGTCGACGGAGGTCGACAGGTT CCATCCTTTTTCACCAGGGCAATCGCTGAGCGGCGGATTGGCCAAGTTCC ACTGTCCGGCCGGCTGATTGCATCCGCCGAGGACCTTGAGCCGCGCGTCA GAATTTTTGTCGCTGTCCTGTTTGTCTGCGACACCAGCCATATTCGACTG GCCCATGAGCATGAAGATGTGAAACGTCGGACTCGCGCTCGGTGCGCCGC CGGTGCCTGCCCCGCTGCTAACGGATCCGGTCCCTCCCGTGGCGTCACCT CCAGTTCCAGCGTTCGTGCTGCCTGTCGCGTCGCCCCCGGTCCCCGCGCT CGTGCTGCCTGCCGTGGCGCCGCCGGTCCCCGCGCTCGTGCTGCCTGCCG TGGCGCCGCCGGTCCCCGAGCCGGCCCCTCCGGTGTTGTCGTCCTCACCG GTCGCGCCGGACTCGCCACAACCGGACGCAGCGATGATGAAGAGGAATGG GAGGAGCAGGAACCTGGGTGTGCCTCGGGTCGTGCGGTTCATCTCGGTCA TGATCGTTACCTCGTCGCGCCGGGGCGCGATCTGAAGAGCATGGCGGAAT CGGTAGGCCGGCGTCGCGATGCCGGCGCGGCGAACCTCGCCCGCAAAGAG WO 00/22139 PCT/US99/23535 212 CTCAGCGCCGGGGCCTACCTTATCGCATCTTGGGCGCTTGGCGTCCAGGA TTCGGCCTTAGACAGCACAAGCAGAAGACCTTTGACACTGGATTTTTTCA TCATCGGCGGCGCTCGTTCTTCGCTGCGCCTCAAGCGCCGACCGTTCGTT TCGAAGCGAAGCGGTTTCACGATCCGGGATCGCGGAAATTTGAAACGGAC 5 GCGTCGCGCGGGCAACGCAGGGGACTCATCACGAGGCAACCGCGCTGCGT CGCGAAATTGGCCAGCCTCTCGGAGTCCCTAGTTCCGTGCGTCAGACGCG TCACCCACCATGTCGAGCTCGGCGCGGCGCTCTACGTGCTTGAAAGACCT CCGCGAGCGCCGCGCTCTGCGCTCCGCGAGCGCACCAGGCTCCCCGTGGA TTCAGGGCAAGGCGGTCGTGATCACGTCCTTCGTGGTCGCCGTGCTCTGG 0 CCGGGGCGGTCGACGCAGGACGGGTAGTACTGGCCGGCCCCGTTGAGCTT CTGGCAGACCCGGTCGCACGACCCGGCGATGCGGATCAGCCCGCACTCCA CGATCTGACCCCCGGAGGTCACGTGGCCCGCGGCGCAGTCGCGCTGGTAG GCGCGCGAGTTGTCGACCGTCGCGCTGTTGTAGCAAGCGTTGATATAGGG TTGCGCGGCGAACAGGTTGCCCCAGAAGGCCCCCTCGACGTCCGGATAAT 5 CGATGAGCTCCTGGCTGGAGGAGAGCGTCTTCAGCGGATCCCGCAGCGAG CGGGCGGAGAGGAGCACCGGTACTTGATAGTAGTTCACGCGCGCCGCCAC GCAGCTGGACACGATGCGCTGCCCTGCGTCGTCGAGCGGCCCGCTCGCCC ACGCGGGCGCGACGCCGAGCAGCCCGGGGTAGCGCTCGTCGTGCCTCTTG CCGTTCGAGTCCGTCCACGAAAAATCGAAGGAGGCCGTGCTGCTCAGGGC 0 GCAGCTCGCCGCGTAACGCAAGAAATCGCGCGCCAGCGCGCCGCTCGGCC CGGGATCCTGGATCGCGGCGAGGTTCCGCGCGCTGAGGCCGCTCAGGTTC AGGGCGTTCAGGTTCAGGGCGTTGAGGTTCAAGGCGTTGAGGTTCAGGGC GTTCGTGCTGAGCGCGTTGCCGCCCACGAGGGCCCCCTGGGATTCCCCCA CAGGCTCGCCCCACGCATCGGCGTCCACCACCTCGGCGGCGCAGCCCGAC 5 AGCACCCCTGCCCAACCAAGCACGATGAATGTCCGCTCGAGAGACATGGA TTCCCCCGTGTTCCTGGCGCATGACCCGACGGCGCCCTGCGCGCGGCGCG CGCGGGCTCCCATCGATTCGCTGGATGGGTTCAATATTCTACTTTTTCCC GCGCTCTCGCGCCGGTGAAAGTCGCTTCAGCGGCGGCGAGGTCGATGTCA GGAGCGTCCGACTCCGTCGCTCTCGTCAGCTCCGCGTACCAGCGACGGAG 0 TCGCCCGCCCATGACGGTCGGAATGGTAGAGGCGGCCGCGAGGGCGCGCT WO 00/22139 PCT[US99/23535 213 CGAGCTGCGCCCGGGCGTCGGCCG:CCGGCCGCGGCGCAGGGCGGCGAGC GCCCGCGCCTCGAGCACCTCGATCC-GCTCCTGCCCGACCGAGCAGCGCGC GGAGCGCTCCTCGAGCGCGGCCCAC-GCGGCGCGGTCGTCGTCGCGGGTCG CGAGCTCGATCATCGCGCAGAGCACGTCCTCCGAGGGCTTCAGCGCCTCG 5 CACCCGGCGTCGTCTCGCGCCGC\CC-GGAGCCGCAGCGCGATCCGGCGAGC GCCCGCCTCGTCGCCCTGGTAGAG-:iCGCAGGCGCGCGATCAGGAGCGTTA CGACGACCGGCGCc3TGGCGATCGC C-GCAGCGCGGCGCTATCGCCTGGACG GCGCGCGCATGGGGCCTCGCGGCC-GCGAGATCGTCCATCAGGTACAGGTA CTCGGCGAGGTTGTAGCGGCCGACGAGCTCGkIACGCGGGCTGGCCGAGCT o CGCGCCCGAGCGCGATc3GTGCGCrn"CGAAATCGGCGATCATCCCGGCGCGA TCGCCCTGGAGCGCCCGCGCGAGC 'CCGCGGTTCTTGAGCGCGGCGCCGAG GTGCATGAGATCGCTGCGCTCCTC-GCAGCTGAGGATCACCGCGTCGAGGT CTCGCGCCGCCTCCTCGACGCGGC CGAGGCTGGCCAGGATGAAGCCGAGC AGCAGCAGGGCGATGATGTGCGTCTCGTGGCCCTCGTCCCCGAGCCGCGC 5CGCCTGCGCCCCGGCGCGCGTCAGC-ACCGCGGCGGCCTCGTCCTCGCGGT CGGCGCGGTGGAGCGAGCGGCCCAC-GCCGAGGAGCAGGCGGGCGCCGAGC AGGGGCGAGGCCACCCGGCCGGCGAGGCGCTCGGCGGCCGCGACCCGCTC GCGCGCGGCCCGGTACTCGCCCGTC-CAGTCGAGGATCATGGCCTCGTCGA GGAGGAGCTCGATCTCGGCCCCCC-CCTCCGACGCCGCCGCCGCCGCCTCG 0 CGCGCCGCGGCGAGGTCGGCGAGG3:'-CCTCGGTGTGGCGCCCGAGCCGGAA GCGAGCGAGGCCCCGCGCTCGGCGCCTCCTCGGGGAGCAGCGCGCCGAGCA GCGCCTCGACGCGCCCGTAGCAGCCC"'-TCGGCGTCGAGGTAGGCCCGGCGC GCGGCCGCGAGCTCGGCGCCGCGG3DCGAGGAGCGACGCCGCGCGGGCGGT CAGGCCGCCGCGCTCGCAGTGCGcCGCGAGCACCAGCGGATCGGCCTCGC 5CCOCGGCCTCGAGCCAGTCGGCGGC-GAGGCGGTGGCCGAGCGCGCGATCG GCAGCTCGCCGCGTAACGCAAGAA- TCGCGCGCCAGCGCGCCGCTCGGCC CGGGATCCTGGATCGCGGCGAGGTT-CCGCGCGCTGAGGCCGCTCAGGTTC AGGGCGTTCAGGTTCAGGGCGTTG ZAGGTTCAAGGCGTTGAGGTTCAGGGC GTTCGTGCTGAGCGCGTTGCCGCC C-ACGAGGGCCCCCTGGCATTCCCCCA 0 CAGGCTCOCCCCACGCATCGGCGT-CCACCACCTCGGCGGCGCAGCCCGAC WO 00/22139 PCT/US99/23535 214 AGCACCCCTGCCCAACCAAGCACGATGAATGTCCGCTCGAGAGACATGGA TTCCCCCGTGTTCCTGGCGCATGACCCGACGGCGCCCTGCGCGCGGCGCG CGCGGGCTCCCATCGATTCGCTGGATGGGTTCAATATTCTACTTTTTCCC GCGCTCTCGCGCCGGTGAAAGTCGCTTCAGCGGCGGCGAGGTCGATGTCA D GGAGCGTCCGACTCCGTCGCTCTCGTCAGCTCCGCGTACCAGCGACGGAG TCGCCCGCCCATGACGGTCGGAATGGTAGAGGCGGCCGCGAGGGCGCGCT CGAGCTGCGCCCGGGCGTCGGCGCGCCGGCCGCGGCGCAGGGCGGCGAGC GCCCGCGCCTCGAGCACCTCGATCCGCTCCTGCCCGACCGAGCAGCGCGC GGAGCGCTCCTCGAGCGCGGCCCACGCGGCGCGGTCGTCGTCGCGGGTCG D CGAGCTCGATCATCGCGCAGAGCACGTCCTCCGAGGGCTTCAGCGCCTCG CAGCCGGCGTCGTCTCGCGCCGCGCGGAGCCGCAGCGCGATCCGGCGAGC GCCCGCCTCGTCGCCCTGGTAGAGGCGCAGGCGCGCGATCAGGAGCGTTA CGACGACCGGCGCGTGGCGATCGCCGCAGCGCGGCGCTATCGCCTGGACG GCGCGCGCATGGGGCCTCGCGGCCGCGAGATCGTCCATCAGGTACAGGTA 5 CTCGGCGAGGTTGTAGCGGCCGACGAGCTCGAACGCGGGCTGGCCGAGCT CGCGCCCGAGCGCGATGGTGCGCTCGAAATCGGCGATCATCCCGGCGCGA TCGCCCTGGAGCGCCCGCGCGAGCCCGCGGTTGTTGAGCGCGGCGCCGAG GTGCATGAGATCGCTGCGCTCCTCGCAGCTGAGGATCACCGCGTCGAGGT CTCGCGCCGCCTCCTCGACGCGGCCGAGGCTGGCCAGGATGAAGCCGAGC AGCAGCAGGGCGATGATGTGCGTCTCGTGGCCCTCGTCCCCGAGCCGCGC CGCCTGCGCCGCGGCGCGCGTCAGCACCGCGGCGGCCTCGTCCTCGCGGT CGGCGCGGTGGAGCGAGCGGCCCACGCCGAGGAGCAGGCGGGCGCCGAGC AGGGGCGAGGCCACCCGGCCGGCGAGGCGCTCGGCGGCCGCGACCCGCTC GCGCGCGGCCCGGTACTCGCCCGTCCAGTCGAGGATCATGGCCTCGTCGA 5 GGAGGAGCTCGATCTCGGCCCCCGCCTCCGACGCCGCCGCCGCCGCCTCG CGCGCCGCGGCGAGGTCGGCGAGGGCCTCGGTGTGGCGCCCGAGCCGGAA GCGAGCGAGGCCCCGCGCTCGGCGCTCCTCGGGGAGCAGCGCGCCGAGCA GCGCCTCGACGCGCCCGTAGCAGCCCTCGGCGTCGAGGTAGGCCCGGCGC GCGGCCGCGAGCTCGGCGCCGCGGGCGAGGAGCGACGCCGCGCGGGCGGT CAGGCCGCCGCGCTCGCAGTGCGCCGCGAGCACCAGCGGATCGGCCTCGC WO 00/22139 PCT/US99/23535 215 CCGCGGCCTCGAGCCAGTCGGCGGCGAGGCGGTGGCCGAGCGCGCGATCG TCCTTGGTGAGCTGCGCGTAAGCGCCCTCGCGCAGGAGCGCCTGGCGGAA GGAGTACTCCTCCTCGCCGGGGAAGCGGCCCTCGCGGTGGCGGACGCAGA GCTCCCCGGCGACGAGCGCGGAGAGGTGCTCCGCGAGCGGAGCGGCCTCG TCGCCCCCGAGCAGGTGCGCGACGGCGCCTCGCCAGAACACCTCGCCGAG CACGCTGGCGGCCCGCAGGATCCGGCGCGCGGGGGGCGCGAGCGCCTCCA GCCGGACCTGCACCATCGCCACCACCGTCTCGGGCAGCGCGTCGCCGCGG CCCTCCGCCGTCGCGCGGATCAGCTCCTCGAGGAAGAACGGCTGGCCCTC GGACTGGGTGACCAGACGATCGATGAGGGCCCCGTCGGCCGCGTCGCCCA GCGCCTCCCGCGCGAGCTGCGCGCACGCCCTCGGCGGGAGCTGCCTGAGC CAGAGCTCCTGCCGCCCGCGCTCGGCCCAGAGATCGGGGTACGCTTGC, or their complementary strands, (b) DNA-sequences which hybridise under stringent conditions to regions of DNA-sequences according to (a) encoding proteins or to fragments of said DNA-sequences, (c) DNA-sequences which hybridise to the DNA-sequences accord ing to (a) and (b) because of a degeneration of the genetic code, (d) allele variations and mutants resulting by substitution, insertion or deletion of nucleotides or inversion of nucleotide segments of DNA-sequences according to (a) to (c) , wherein the variations and mutants offer isofunctional expression products.

13. Peptide encoded by a DNA sequence according to claim 12 selected from the group consisting of WO 00/22139 PCT/US99/23535 216 Seq ID No 92 >Contigll_002 591 amino acids MW=63639 D pI=5.80 numambig=0 MLDVWSTSDQVACRLHCAGAGPSASLELRYDASAGARRDAERLAERLAALLEDLSRHPER 5 PVAQGEYVGPGEPAEIEAWSRGPAMELPSACALHRWFEERAEQHPDVVAVRSEGKSLTYG ELERRANRLASCLRRRGVGLDTI VGVCVPRSEDMVVATLAVLKVGGAYLPLDHEYPGERL AFMMRDARARLLVTHDAIADELPTGGWTTLLLDAEAAEIAACSDARPAVSPPPDSGAYVI YTSGSTGTPKGSLISHRAIVNQMQWIQRYWALTADDRVLLKAAFGFDVSVWEIFWPLSFG ARIVVAPAGGHRDPEYLRRLVRDEGATTAYFVSSMLAAFLGGPEQPFPASLRKVLVGGEA 0 VPLDLVRRFYAKHDGDLINMYGPSEAAIAVTGCVLPSDPRVTWVPLGAPVANAEVFVLDG AMRRPAIGALGDLYIAGAPLARGYVGQPGLTAERFLPDPCARAAGGRMYRTGDVARFLPD GMLEFQGRSDHQIKLRGHRIELGDVEAQIRRVPGVGQAAVVLREDAPGDARLVAYVVLDG DAAGDAPDVRAGLKASLSAYMIPSSVVRLYALPMCSERLAFTGSSYAGCLL* 5 Seq ID No 93 >Contigll_007 361 amino acids MW=38862 D pI=10.42 numambig=0 MSDHEMTGFSLSPQQRAIRALDREAGAPGCRTLAVVAVTGPCDEGRLSAAALALAERHEI LRTRLVEAGRARPRRWSASPASRGRQQDDWVGCSEAEQGERMSRLVARLSEDRGADDGLR VGLVRVGPEERRLVLAAPAWCVDEESIAPLVRELCASTAGAGAPPEQQYADVAEWLNGML 0 ESEDAGDGRRFWAERRSHFGPPLHLAFSRGGAGAGAGSGRARVDLGQGGMAQVERWSSSW QVPQRIVLLALWASLLWRMSGGNEPEVTVAVRFDGRSLDALAGAVGPFARFLPVRIEISA SDTLADVARRLALAEAEAAAHQDAAPGVSHRMSWGLLRRGGRAGAVARRRAGPRARRLEH V* 5 Seq ID No 94 >Contigll_012 882 amino acids MW=95015 D pI=12.69 numambig=0 MARALYAQEAAFRSAFNACAAAARARGLDLGEVVFREGEGDGRTLLGTALAQPALFAVEL ALARLWMSWGIEPAAMIGHSLGELVAACVAGVFTLEDAMSLVIDRGRFMQAAPAGSMLAV GLPAADVEGLLEAGLEIAAVNSPKLTVVAGPASAIRDLAARLEAREVFARPLQTSHAFHC 0 ALIDGAVAPFLESVRRARLSPPEIPVVSNVTGALLTDAEATDPAYWARHLRQPVRFSDGV WO 00/22139 PCTIUS99/23535 217 EALPAS GHALFLEVGPGRGLTTLVRQTLAGRGGAJATASLGS THAASEFPAS LAEALGQLWE AGHAVDWTARPRGRPPARSSACRRTRSSGRGTGSRPAAAPPPPSRRRPTRPSRPRRTPSR RRRSPARTPGPRSPRRRPS PSARS PAT WERPPRRPRDRRPRRLLRPARRLARRDPGDVPD PRAARRRAPAAGALPGADGRGARGPGRRPAPRRGAAARVP PDPADPPRRPAPAXTVRAAPA VVRAAQGQPRADPRRAPQVDAPGADQQRAPR ARGPGAVPDVRPRAPRGRGPRRGGLGARPRGE PRAVRPE PPAAP PPAGHPEAPRRARHRA RRAPRRVRRLVGRRLRRPARRALRRLRAGPAFPAAGAPGAVRRLRRS PAGVAVRRGPGGR APVLDDEALGRAAPGPRAGRPAGGADVARGAE PRRRGRAHP PDQGVLPAGGDLPLHG PARRVQARPAPAHRARGPRRGHRRRE PE PRRDPADDRLLRQPAP.APDRLRGRPDVRPAGP PRARRRARGVRAPGPAVRPARRGPAJAEGGRRPAPLRREVRHAQPARP PDEARGARARGA GGRGDHDGVRLRPHCRRGRRLVPLRRPAQQBAVPGGDGRQFP * Seq ID No 95 >Contigll 021 1213 amino acids MW=131017 D pI=12.40 numambig=0 MRRRAPLGRARDRGARSRRRRHELAGRRARR LPAPGPS PPRGAPQAPPGARRGPPRPH1&VGGRRDDRLARGHPAPRRRRGPAVARPRAP AARRKHGRPGLRDLHVRVHGAAQGRDDRP PRRGEHGPRHQP PLRRRPGGPGAPALVAELR PVGLRRVRDARRRRRRRD PRPY PRLGS GALAPARGARAGDRVELGPGADGDMIGRVPRRG RPGAVVAP PRHDERRLDPAEAPRSHPRGLPPAPRRE PRRRDRGVDLVDRPPDRGRRPGVA QHPLRPPAREPAHLPARRGAGAVSDRGPRRDPHRRDRRRART LARRGADPGAVPEAPHDR RAAVQDRRPGPLLRRRDHPAARAHRP SGEDPRLPHRARRDRGRPPAAPLGPAGGRGGEDR SVGREAPGRVRRRRRRRWRPAPRLRPEEAAGVHDPRGGRRPPGAERERQGGPRRPAGS RRRARRPDD-,HLAGLGRRRRPPALLARAAPRA RGARARRGRRGAGRVADRPVPVDHPATGAARRGDGQGPAGRRRGARRGAPRPATP PG ARIAMSEPIETEDGGSDIAIVGMAGRFPGAPSVDALWENVRRGVESIARFPESEREEPPV GASAAPGAPVVCAGGLLDD IDRFDASYFGYS PREAQLMDPQQRLFLECAVAALEDAGCDP ARPPGATGVFGGCGSNTYLLQLLSHPDLAATVDPHALMLASEKDYLATRVSYKLDLHGPS VVVQTACSTSLVAVHMACESLLGG-QCDLALAGGvs IGI PQKRGYPYVPGS ICSPDGRCRP FDAR-AEGT-VGGSGVGIVALKRLADALRDRNTVHAVI RGSAVNNDGGRKVGFMAPSVDGQA AAISEAQSVAGVDPGS TGYVEAHG-:TATAIGDPIEVEALTQAPRRKTPRKAYCALGS IKAN WO 00/22139 PCT/US99/23535 218 IGHLDAAAGVAGLIKAAHVVRSGEIPPCVHFEAPNPKLDLAASPFFVPREAAPWPRELRP RRAGVSSFGIGGTNAHVVLEEPPPLPPRAPAPERDHVLTLSARTPEALSTACAQLAAHLE ATDVPLDDVAFTLQTGRAEHPYRPAVVARTRAEAIQGLAREGASALARPDEPRPSSRSRA RARRPSGWPARSTRRRRRSGAPSTARRRRGRAASISARSSSARARATGARCSAPRWRSP 5 RSSPSSSRSPGSG* Seq ID No 96 >Contigll026 3079 amino acids MW=332984 D pI=5.97 numambig=0 MLTVVDHHVVVEYWSFALIVRELGELYSALRAGRPPQLPPPSSFFAAGVSCPSPREAAGG D AEYWRKALDGATTAIDLPRDRARHDAGARRGpAHAITLPKPLTGALARLARERGTTLFSV LLSALTVLLHPASGQSDLVVGVPSAGRHDDESARAFGYFVQMLPVRVALRGAASFDALVA RVRDAFLDALAHGDSALRHLLARAQGEAQRDALFDVAFAFQSTPPSLDARLSALAIGVGD VRIAQGELELTTLADEQAAAEFDLALFAAELDAGIALRFEYDQQLFDPATIERMARHFVV LLESAVEHPGRPLSELRMLSDAERALLLDDWSGAAAARQAASAPAPACVHALFEAHAARQ D PDATALEFGHQRFTYAQLSTWSTELALWLRDRGVGPGSVVGVCIERSPRMVAAQLAVLKA GAAYASLDPANPPARLAEMLADCRASLALTSSQASHKLTAAPCPVHLVQDGACAPSTHIP LVSRPDDLAYVLFTSGSTGTPKGVCVRHASLSRLVSFLHLRLDLSPSDRWTQVASSGFDA SVYEIWTPLACGAALLLADDDALRSPTALVSWLVAQRATLSFMPTPLAEACFEQDWTGSA LRAMTVGGDKLHPLRRPLPFRLFNMYGPTEATVITTVAEIADLGAEPPLGRPVDSALVYV J LDPHMQPVPPGALGELYIGGACLAQGYTRTDLTAERFLPDPFGQPGARLYRTGDLVRWRP DGQLAFAGRRDEQVKLRGRRVELGEVESVLRRLPGVREGIVVLHGQGSAAHLIAHVVPDA HPPSERDLREGMARLVPDALVPAHFVLLPALPMSLSGKVDKKLLPAPPAAHADYEPPSGE LELELAHIWQSVLHLDRVGRHDSFFDLGGHSLLAMQVLGRIESSLGIRTTLRTLFEHPTL AQLASHLSSGAASTSAAAATALERGLTRPDGPSSPRVATPEEPFALTEGQRAMWLECQKS 5 ADGALYNLGRTVRLGAGVDVAALRRAFEGLVERHEALRTTFLTRDGHPLQQVHRHVALEW AEEPAMALDEREIVARADEVRRAFDLERGPLLRVHVWRRGEGQPPLLTVVVHHLVVDYW SFALLVRELGELYSALRAGRPPQLPPPSSFFAAGVSCPSPREAAGGAEYWRKALDGATTA IDLPRDRARHDASPRRGRAHAITLPKPLTGALARLARERGTTLFSVLLSALTVLLHPASG QNDJLVVGVPSAGRNDDESTRAFGYFVQMLPVRVALRGAASFDALVARVRDAFLDGLAHGD SALQHLLAEPRGAARRGGALFDVAFAFQGALPSLDPRLAALTTGAEDVRIAQGELELTTL WO 00/22139 PCT/US99/23535 219 ADEQAAAEFDLALFAAELDSGIALRFEYDQQLFDPATIERMARHFVLLLESAVEHPGRPL SELRMLSDAERALLLDDWSGAAAARQAASAPAPACVHALFEAHAARQPDATALEFGHQRF TYAELSTWSTELALWLRDRGVGPGSVVGVCIERSPRMVAAQLAVLKAGAAYASLDPANPP ARLAEMLADCRAALVLTSSQASHKLTAAPCPVHLVQDGACAPSTHIPLVSRPDDLAYVLF D TSGSSGTPKGVCVRHASLSRLVSFFQHLLALSPRDRWTQLASSGFDASVYEIWTPLACGA ALLLADDDALRSPTALVSWLVAQRATLSFMPTPLAEACFEQDWTGIALRAMTVGGDKLHP LRRPLPFRLFNMYGPTEATVITTVAEVADLGDEPPLGRPIDSALVYVLDPHMQPVPPGVL GELYIGGACLAQGYTRTDLTAERFLPDPFGQPGARLYRTGDLVRWRPDGQLAFAGRRDEQ VKLRGRRVELGEVESALRRLPAVREGVVVLHGQGSAARLIAYVVPGADPPSERDLREGMA RLVPDALVPAHFVLLPALPMSLSGKVDKKLLPAPPAAHADYEPPSGELERELAHIWQSVL HLDRVGRHDSFFDLGGHSLLAMQVLGRIESSLGIRTTLRTLFEHPTLHQLADRLSSGAAS TTAAAATVPASEIAPSLGRAPADEPYPLSYEQERLWVLEQLLPGGTAYNVVQAVRLRNLV DVDALSSALAALVRRHWSLRTVFVASPTPAQKICEPEAAPAEVVDLRGTPPDEAEAAApA WASREQATGFDLARGPVFRARLFRLDHDVCVLVLSTHHIVTDAWSFQPLVRDLAELYRRA 5 RGGGPADMPELPLQYVDFAVWQRRHLAGKRLADKLAHWTATLRGLPVLELQTDRPRPPVQ TFRGAERVLPLDARLVAQLDELARSRGATRFMVLLAALGVLLRRSSGQDDLAIGTAVANR PRPELEPLVGFFVNTIVMRLDLGGDPTFEELLSRARKVALEAFEHQDAPFEKVVEAVNPR RDLSRSPLFQVMLVVQNAPTEALELGEVRIEPLDLPVEATRFDLRFSVEPRGGRDVISLQ YNVDLFDAATIDRMLATMQSVLSRATQDPAQRVRALSVAPEDRERALVAWNDTAVATPDH D LRLEEPFFERAVEQPDACAVVDAERRLTYGELARRAEAIAAAASRSGATANALVAVVMEK GWEQVAAVLGVLPAGAAYLPLDPRLPEERLRHLLEHAEVRLVLTQSAVDGTIAWPAGIER LAVDADERWREQPVARRPPGGSTDDLAYVIYTSGSTGLPKGVMIDHRGAVNTVLDINRRF DVGPEDRVLALSSLSFDLSVYDVFGTLAAGGAVVIPDRTRASDPGHWRELVERERVTVWN SVPALMEMLMDASPGAGDPALSSLRLVMMSGDWIPLKLPDRIRAACRAPRVVSLGGATEA D SIWSIAHPIADVDPAWRSIPYGRPLANQHTYVLDEGLEPCPIGVPGEIHIGGIGVALGYW RDEARTRERFLKHPTTGERLYRTGDLGRYFADGTIELLGRTDHQVKIRGFRIELGEIEAA LAQHPSVEQAVVAAKTDPSGEKRLVAYVVGADGDGAALRDFVRKKLPEYMIPAEVVVLPA LPLSANGKVDRAALPDPAAVAPRAAAVAPRTATERLIASVLAEVLQVEAVGVTDNLFELG FTSLLLVRAQRLLAERIAARAPDEGAAAQAVSLTDLFQYPTIEQLAQRLDAATVKAEPAD J VGAQRAEARRDARRRRGRG* WO 00/22139 PCT/US99/23535 220 Seq ID No 97 >Contigll_011 544 amino acids MW=60164 D pI=9.10 numambig=0 MMSRIRAQLGVELPLRALFQGPTVAALAAQVDAARRGEARRREFPPIARIPRDGPLPLSF AQHRLWFVDQLEPGSPAYNIPFVVRATGRLDVDALRRSLFEIARRHEALRTTFSARDGVP FPVVAPEARVPFRMSDLEHLAGEALDAAVSALVLEESLAPFDLSRGPLLRVRVIRKRHDE HVIALVVHHVVFDVWSVGVFVGELAALYGGFAQGQPSRLPELPAQYVDFAAAQRAWLSGE VLEGELRYWTTKLSGALRRARVPVDHEPAGRRTWRGARRSLDAGAELTRQIKAFCEREAI SPFMALLAAYKLVLHQRTGLEDLVVGTDVANRNRVETEPMIGFFVNQLVLRTDCGGDPTF GALVRRVRDVALEAFEHQDLPFDRLVEALRPKGAVGHVPLFDAKFVMRNVHVPPMKLEGL ELEALEGEATTTAFDFVLTVAEAGGSFRFGVEHSSELYPAATVDNFLSDYRQILATATAR PDTPVSELRGELERAAAARRELERKAARGAALDKLTSARRRAVTLPRPGAPGEAKTSPKD DLDE* Seq ID No 98 >Contigl2_001 514 amino acids MW=56145 D pI=8.82 numambig=0 PPAVRRYVADRRPEQLPALAPEEREAAARRLSALGAAPPQVRRRGLTRAPLSYGQSRIYF LEQLSPGKPLFNVPGAVRLRGPVDVARLSAAFGEIVRRHDALRTSIANVDGELLQIAQPH AGFALDVVTSTPEEAAELDRRLpAEAWRPFAIGAPPLLRATLFRLAEDEHVLLVTMHHVV SDDWSLGVILRELLALYAGRSLPPPRLQVSDFAAWQREMVESGALDGQRAYWRERLRGLS RASISAGGGAEAPSHDPSGAIEEIALSPDKAAALEALARREGATLFMVLLALLDLVIHAR SGALDIAVGTPIANRNRPELEDVVGLLTNTLVIRVDLARAGAFRDVLARARVQALDAFAN QDIPFDVVTQDLKQERDHAQHPLFRVWLALQNAPKPALEVRGLRVEPLPLRPELVHFEVA LLLWPADDGSVVGHFEFRRDRVDEGARKEIAAAFTHLVDAVIARPDAPVSTLVEGARAEA ARAQAALGEAFARAATARLGQLRRRSAGDRTPRE* Seq ID No 99 >Contigl2_009 582 amino acids MW=65555 D pI=8.72 numambig=0 MREPSSTPNWRNFGSNLPAGSDSVPPGEGFPIKKILALNLGKWKDTAGLQIAQALHLFEY GYKRYREGKFVLRATSDLGLGAIFESIDNWESFDQFEEFFKPWTFIRKPLVATRWAEDAE WO 00/22139 PCT/US99/23535 221 FGRQRLVGINPAHIRRATPADLADFVSGAEPKPIAIADGRTLEEVREGGQLYFLDYRIFK DIVDTDVQEELGKYPLAPTCMLHQTAAGELLPVAIRLVHSRPGKGAHPDKIFTPSGPSDD WLTAKIAVASADAIYQGQVTHLLYAHLIVEPFAVSTYRNLPATHPLHQLLRPHFFNTLAI NELARRRFLGRGRFFDITSSVATMGSFELLTRAYTGKGIKGYGGKPWRFYESALPRDLSA 5 RDVRDLVGYHYRDDALLHWDAIQEYVGQVLKIAYPTPGSLSSDASLQRWIHELVSPQLGG MDSLLPPERADQLEKLTSLDDLIAIVTNIIFTATAYHAAVNFGQTDYYTWIPNAQFATYR SYGDVLNGSEKRQFKPLERLPGRAQSIRQMVLSRSLSMGPPLTSESLMTMKCLLQDPAAK QAFARYRERLAHIEREITERNRAREQPYLYLLPSMVPQSVAI* 0 SEQ ID No 100 (>ORF1) VSQRTSCYLRGGGVCSMNDAFLALERNERNRPSTVIDLLRQPAEAEPARPIYCFLESGDVEAG ATWVTLREIDERARTVAALLQASGVAPGARALLLYPPGIEYITAFFGCLYAGVRTVPAYPPDL GRLERTLPRVASIVADARAEAALTSSAVAGIVASLPASAAAAALQRLRWIATDGPSPGPIEGP GAALRPESVAFLQYTSGSTGEPKGVMLTHGNLLHNSRLIAHGFDLTSPDPVGVIWLPPYHDMG 5 LIGGILQALYRRIRVALMSPLSFLQRPMRWLRAVSALGASVSGGPNFAYDLCVRKSSEEERAA LDLRSWEVAFTGAEPVRADTLDRFARAFAVSGFRREAFYPCYGLAEATLIVSGGARAEAPVLA RLAPEEVELGRAVASAAEGARVFVGSGPALDPRAVAIVDPAGNELGPGEIGEIWVSGPSVAVG YWGRPEETEATFGATLAGSAAPRYLRTGDLGFLRGGELFVVGRSKDLIILRGRNHFPQDIEKT VESSHRAVRPGCSAAFSVEHEGEERLAVVCEVDPRVAADPREIVAAREAVTAEHQLVAHAVAL D IAPGALPKTSSGKVRRRECRRAFLEDALGERHVAFAPELLDDASPPDDAPPETEEPSGRSLLD ALRSTLARALRLDAGQIDDALPISRFGLDSLAAVELQHAFQVRTGRAIPLTSILRGGSLRLTR EITRLDGPSSPRVATPGGAVCADRWGTGRFGSSAISRPMERFTTWAGRSGSVPAFKRVDLRRA F 5 SEQ ID No 101 (>ORF2) VYSSAYVLFAVCAGTTRVASAPETAGFPLECVGDDGTVLGPDSFVVGYTQVYVFKKERLNTNP PIDGFTLKLDGNEVAPGEDGLPVVKRCVRSEEQAQGCGRTEPAEDECTTYEIEAVVPEKAAEV DEEAAGLGGPPAREAIWVDYYTDGGEFDGARRLVSDTTGASRGGNGTTWTPPSEPGRVSLWAV VHDTRGGASVTRREVQVE WO 00/22139 PCT/US99/23535 222 SEQ ID No 102 (>ORF3) VVGTVLSAGTGEPLPDIAVTLVRPDGGREEAKTDQGGKFRFKNLPPGKYRVEVAAAGFEPFAA EEEIAAGEAIEVRYRISLAAPQDGKAPGIEVTVQGERPPREVTRRTIERREIDRIPGTGGDAL RSLQSLPGVARSGFGLLIVRGSAPQDTLTFVDRTPVPIIYHFGGLSSVVPTEMLEKIDFYPGN 5 FSAVYGRAMGGIVDVGLRSPKQDGKYHGVVQLDLIDGRVLLEGPVPFLKDWTFIAAGRRSWVD AWLGPVLKEAGSSVTQAPVYYDYQFVLEGRPSASERVRASFYGSDDAFKITLDKPPEDEPALT GDFGLHTAFQRFQLSYENRIGSRDRLLWSMALGRDIADFEISPLAFNVVSTSLDLRLELSHRF ARYLTMNVGTDLSGGVATVNIPAPSQQPAGHPSNQPFSTYPFQDRSFDGAYSRPAAYAELEVV PSPRARIVPGVRVDYALDTQTLDVSPRVNARYDIRSGFPRTTAKGGVGLYYQAPQFAESIEPF 0 GNAELKSNRAVHYGLGVEQEITPQIEVTLDGFYKQLDRLVVFSPEKDDYADGTGYAVGGELLL KYKPDERFFGWAAYTLSRSVRKDGPDEEEHLTQFDQTHVLTVLGSLRLGRGWELARFRLVSGN LQTPYVCDPEEKGCNPNRVNAIYHASSARYSPIPLGGDYSERMPLFHQLDIRADKTWKFKRWQ LGLYLDIQNVYNYMAAEGISYNFNYTKREYVTGLPFLPTLGLRGDF 5 SEQ ID No 103 (>ORF4) VIAVDNNPEAVDAVKDKTSAAFVGDATVHKVLEGIGAQYVETAIVTFGEHFEPSVLCVASLVR MGVRIIARAATDRQADILRAVGATRVIQLETEMGRRVGADITMPLAQDLLDLASHYRVVPWNA HGPLVGQTLAGSKIRQRYRINVLGVRPHTNKRPGDKPRLEAPTPDYVIRDGDTLLLVGDSDDV SRFVAEVGG 0 SEQ ID No 104 (>ORF5) SGSSGGGSSAEGSRCQPSGGGPHWLLEGETVTFPVTCASGLALAGDAFEVGPLPEGAAYDPIA REVTFSPGLDQAAVYDIEIRVAQTSEVGRVKVGVADAFADPSNVPVVDPTRYPEEYGLPVLFL SPVPEDKEYAPATVIYRGHTYAAEAELRGESSLSYPKRSYTLKFPKDDKFNEPDEAGGFTDRR 5 KVVLITTFDDNSYVRQRLAYDLWNRLDPEHIQIKTYSAVLYLDGEYAGLYTVADHVDGYLMED HGYPQDGNLYKAVSHDANFALTDRSGDPKDTLHDGFEKKEGAPAEGEPEAFSDLEDLVSFVAE SDDATFAAEIGSRIDLRDYEDWWIFVTFIVANDSAGKNSYHYRDPAADGVFRYAPWDFNASFG QSWETEREPASDRVDYRDVNLLFERLLEEPSIGDPLRARYDQVLRGALAEAEIHAIVDGYVER IDASARRDEARWGEAYRSYEGWSWRDDFTTYEEEIAYLK 0 AWISERWQHQDELY WO 00/22139 PCT/US99/23535 223 SEQ ID No 105 (Contig 11 >ORF1) VLDVWSTSDQVACRLHCAGAGPSASLELRYDASAGARRDAERLAERLAALLEDLSRHPERPVA QGEVGPGERAEIEAWSRGPAMELPSACALHRWFEERAEQHPDVVAVRSEGKSLTYGELERPAN RLASCLRRRGVGLDTIVGVCVPRSEDMVVATLAVLKVGGAYLPLDHEYPGERLAFMMRDARAR LLVTHDAIADELPTGGWTTLLLDAEAAEIAACSDARPAVSPPPDSGAYVIYTSGSTGTPKGSL ISHRAIVNQMQWIQRYWALTADDRVLLKAAFGFDVSVWEIFWPLSFGARVVARAGGHRDPEY LRRLVRDEGATTAYFVSSMLAAFLGGPEQPFPASLRKVLVGGEAVPLDLVRRFYAKHDGDLTN MYGPSEAAIAVTGCVLPSDPRVTWVPLGAPVANAEVFVLDGAMRRPAIGALGDLYIAGAPLAR GYVGQPGLTAERFLPDPCARAAGGRMYRTGDVARFLPDGMLEFQGRSDHQIKLRGHRIELGDV EAQIRRVPGVGQAAVVLREDAPGDARLVAYVVLDGDAAGDAPDVRAGLKASLSAYMIPSSVVR LYALPMCSERLAFTGSSYAGCLL SEQ ID No 106 (Contig 11 >ORF2) MSDHEMTGFSLSPQQRAIRALDREAGAPGCRTLAVVAVTGPCDEGRLSAAALALAERHEILRT RLVEGRARPRRWSAS RASRGRQQDDWVGCSEAEQGERMSRLVARLSEDRGADDGLRVGLVRVG PEERRLVLAAPAWCVDEESIAPLVRELCASTAGAGAPPEQQYADVAEWLNGMLESEDAGDGRR FWAERRSHFGPPLHLAFSRGGAGAGAGSGRARVDLQGGMAQVERWSSSWQVPQRIVLLALWAS LLWRMSGGNEPEVTVAVRFDGRSLDALAGAVGPFARFLPVRIEISASDTLADVARRLALAEAE AAAHQDAAPGVSHRMSWGLLRRGGRAGAVARRRAGPRARRLEHV SEQ ID No 107 (Contig 11 >ORF3) MSRIRAQLGVELPLRALFQGPTVAALAAQVDAARRGEARRREFPPIARIPRDGPLPLSFAQHR LWFVDQLEPGSPAYNIPFVVRATGRLDVDALRRSLFEIARRHEALRTTFSARDGVPFPVVAPE ARVPFRMSDLEHLAGEALDAAVSALVLEESLAPFDLSRGPLLRVRVIRKRHDEHVIALVVHHV VFDVWSVGVFVGELAALYGGFAQGQPSRLPELPAQYVDFAAAQRAWLSGEVLEGELRYWTTKL SGALRRARVPVDHEPAGRRTWRGARRSLDAGAELTRQIKAFCEREAISPFMALLAAYKLVLHQ RTGLEDLVVGTDVANRNRVETEPMIGFFVNQLVLRTDCGGDPTFGALVRRVRDVALEAFEHQD LPFDRLVEALRPKGAVGHVPLFDAKFVMRNVHVPPMKLEGLELEALEGEATTTAFDFVLTVAE WO 00/22139 PCT/US99/23535 224 AGGSFRFGVEHSSELYRAATVDNFLSDYRQILATATARPDTPVSELRGELERAAAARRELERK AARGAALDKLTSARRRAVTLPRPGAPGEAKTSPKDDLDE SEQ ID No 108 (Contig 11 >ORF5) 5 MSEPIETEDGGSDIAIVGMAGRFPGAPSVDALWENVRRGVESIARFPESEREEPPVGASAAPG APVVCAGGLLDDIDRFDASYFGYSPREAQLMDPQQRLFLECAVAALEDAGCDPARFPGAIGVF GGCGSNTYLLQLLSHPDLAATVDPHALMLASEKDYLATRVSYKLDLHGPSVVVQTACSTSLVA VHMACESLLGGQCDLALAGGVSIG IPQKRGYPYVPGSTCSPDGRCRPFDARAEGTVGGSGVGI VALKRLADALRDRNTVHAVIRGSAVNNDGGRKVGFMAPSVDGQAAAISEAQSVAGVDPGSIGY 0 VEAHGTATAIGDPIEVEALTQAFRRKTPRKAYCALGSIKANIGHLDAAAGVAGLIKAAHVVRS GEIPPCVHFEAPNPKLDLAASPFFVPREAAPWPRELRPRPAGVSSFGIGGTNAHVVLEEPPPL PPRAPAPERDHVLTLSARTPEALSTACAQLAAHLEATDVPLDDVAFTLQTGRAEHPYRRAVVA RTRAEAIQGLAREGASALARPDEPRPSSRSRARARRPSGWPARSTRRRRSGAPSTPARRRRGR AASISARSSSARARATGARCSAPRWRSPRSSPSSSRSPGSG 5 SEQ ID No 109 (Contig 11 >ORF6) VVDHHVVVEYWSFALIVRELGELYSALPAGRPPQLPPPSSFFAAGVSCPSPREAAGGAEYWRK ALDGTTAIDLPRDRARHDAGARRGRAHAITLPKPLTGALARLARERGTTLFSVLLSALTVLLH RASGQSDLVVGVPSAGRHDDESARAFGYFVQMLPVRVALRGAASFDALVARVRDAFLDALAHG 0 DSALRHLLARAQGEAQRDALFDVAFAFQSTPPSLDARSALAIGVGDVRIAQGELELTTLADEQ AAAEFDLALFAAELDAGIALRFEYDQQLFDPATIERMARHFVVLLESAVEHPGRPLSELRMLS DAERALLLDDWSGAAAARQAASAPAPACVHALFEAHAARQPDATALEFGHQRFTYAQLSTWST ELALWLRDRGVGPGSVVGVCIERSPRMVAAQLAVLKAGAAYASLDPANPPARLAEMLADCRAS LALTSSQASHKLTAAPCPVHLVQDGACAPSTHIPLVSRPDDLAYVLFTSGSTGTPKGVCVRHA 5 SLSRLVSFLHLRLDLSPSDRWTQVASSGFDASVYEIWTPLACGAALLLADDDALRSPTALVSW LVAQRATLSFMPTPLAEACFEQDWTGSALRAMTVGGDKLHPLRRPPFRLFNMYGPTEATVITT VAEIADLGAEPPLGRPVDSALVYVLDPHMQPVPPGALGELYIGGACLAQGYTRTDLTAERFLP DPFGQPGARLYRTGDLVRWRPDG-QLAFAGRRDEQVKLRGRRVELGEVESVLRRLPGVREGIVV LHGQGSAAHLIAHVVPDAHPPSERDLREGMARLVPDALVPAHFVLLPALPMSLSGKVDKKLLP 0 APPAAHADYEPPSGELELELAHWQSVLHLDRVGRHDSFFDLGGHSLLAMQVLGRIESSLGIR WO 00/22139 PCT/US99/23535 225 TTLRTLFEHPTLAQLASHLSSGAASTSAAAATALERGLTRPDGPSSPRVATPEEPFALTEGQR AMWLECQKSADG ALYNLGRTVRLGAGVDVAALRRAFEGLVERHEALRTTFLTRDGHPLQQVHRHVALEWAEEPAM ALDEREIVAPADEVRRRAFDLERGPLLRVHVWRRGEGQPPLLTVVVHHLVVDYWSFALLVREL 5 GELYSALRAGRPPQLPPPSSFFAAGVSCPSPREAAGGAEYWRKALDGATTAIDLPRDRARHDA SPRRGRAHAITLPKPLTGALARLARERGTTLFSVLLSALTVLLHRASGQNDLVVGVPSAGRND DESTRAFGYFVQMLPVRVALRGAASFDALVARVRDAFLDGLAHGDSALQHLLAEPRGAARRGG ALFDVAFAFQGALPSLDPRLAALTTGAEDVRIAQGELELTTLADEQAAAEFDLALFAAELDSG IALRFEYDQQLFDPATIERMARHFVLLLESAVEHPGRPLSELRMLSDAEALLLDDWSGAAAA 0 RQAASAPAPACVHALFEAHAARQPDATALEFGHQRFTYAELSTWSTELALWLRDRGVGPGSVV GVCIERSPRMVAAQLAVLKAGAAYASLDPANPPARLAEMLADCRAALVLTSSQASHKLTAAPC PVHLVQDGACAPSTHIPLVSRPDDLAYVLFTSGSSGTPKGVCVRRASLSRLVSFFQHLLALSP RDRWTQLASSGFDASVYEIWTPLACGAALLLADDDALRSPTALVSWLVAQRATLSFMPTPLAE ACFEQDWTGIALRAMTVGGDKLHPLRRPLPFRLFNMYGPTEATVITTVAEVADLGDEPPLGRP 5 IDSALVYVLDPHMQPVPPGVLGELYIGGACLAQGYTRTDLTAERFLPDPFGQPGARLYRTGDL VRWRPDGQLAFAGRRDEQVKLRGRRVELGEVESALRRLPAVREGVVVLHGQGSAARLIAYVVP GADPPSERDLREGMARLVPDALVPAHFVLLPALPMSLSGKVDKKLLPAPPAAHADYEPPSGEL ERELAHIWQSVLHLDRVGRHDSFFDLGGHSLLAMQVLGRIESSLGIRTTLRTLFEHPTLHQLA DRLSSGAASTTAAAATVPASEIAPSLGRAPAD D EPYPLSYEQERLWVLEQLLPGGTAYNVVQAVRLRNLVDVDALSSALAALVRRHWSLRTVFVAS PTPQKICEPEAAPAEVVDLRGTPPDEAEAAARAWASREQATGFDLARGPVFPARLFRLDHDVC VLVLSTHHIVTDAWSFQPLVRDLAELYRRARGGGPADMPELPLQYVDFAVWQRRHLAGKRLAD KLAHWTATLRGLPVLELQTDRPRPPVQTFRGAERVLPLDARLVAQLDELARSRGATRFMVLLA ALGVLLRRSSGQDDLAIGTAVANRPRPELEPLVGFFVNTIVMRLDLGGDPTFEELLSRARKVA 5 LEAFEHQDAPFEKVVEAVNPRRDLSRSPLFQVMLVVQNAPTEALELGEVRIEPLDLPVEATRF DLRFSVEPRGGRDVISLQYNVDLFDAATIDRMLATMQSVLSPATQDPAQRVRALSVAPEDRER ALVAWNDTAVATPDHLRLEEPFFERAVEQPDACAVVDAERRLTYGELARPAEAIAAAASRSGA TANALVAVVMEKGWEQVAAVLGVLRAGAAYLPLDPRLPEERLRHLLEHAEVRLVLTQSAVDGT IAWPAGIERLAVDADERWREQPVARRPPGGSTDDLAYVIYTSGSTGLPKGVMIDHRGAVNTVL D DINRRFDVGPEDRVLALSSLSFDLSVYDVFGTLAAGGAVVIPDRTRASDPGHWRELVERERVT WO 00/22139 PCT/US99/23535 226 VWNSVPALMEMLMDASPGAGDPALSSLRLVMMSGDWIPLKLPDRIRAACRAPRVVSLGGATEA SIWSIAHPIADVDPAWRSIPYGRPLANQHTYVLDEGLEPCPIGVPGEIHIGGIGVALGYWRDE ARTRERFLKHPTTGERLYRTGDLGRYFADGTIELLGRTDHQVKIRGFRIELGEIEAALAQHPS VEQAVVAAKTDPSGEKRLVAYVVGADGDGAALRDFVRKKLPEYMIPAEVVVLPALPLSANGKV 5 DRAALPDPAAVAPRAAAVAPRTATERLIASVLAEVLQVEAVGVTDNLFELGFTSLLLVRAQRL LAERIAARAPDEGAAAQAVSLTDLFQYPTIEQLAQRLDAATVKAEPADVGAQRAEARRDARRR RGRG SEQ ID No 110 (Contig 12 >ORF1) D PPAVRRYVADRRPEQLPALAPEEREAAARRLSALGAAPPQVRRRGLTRAPLSYGQSRIYFLEQ LSPGKPLFNVPGAVRLRGPVDVARLSAAFGEIVRRHDALRTSIANVDGELLQIAQPHAGFALD VVTSTPEEAAELDRRLRAEAWRPFAIGAPPLLPATLFRLAEDEHVLLVTMHHVVSDDWSLGVI LRELLALYAGRSLPPPRLQVSDFAAWQREMVESGALDGQRAYWRERLRGLSRASISAGGGAEA PSHDPSGAIEEIALSPDKAAALEALARREGATLFMVLLALLDLVIHARSGALDIAVGTPIANR 5 NRPELEDVVGLLTNTLVIRVDLAAGAFRDVLARARVQALDAFANQDIPFDVVTQDLKQERDH AQHPLFRVWLALQNAPKPALEVRGLRVEPLPLRPELVHFEVALLLWPADDGSVVGHFEFRRDR VDEGARKEIAAAFTHLVDAVIARPDAPVSTLVEGARAEAARAQAALGEAFARAATARLGQLRR RSAGDRTPRE D SEQ ID No 111 (Contig 12 >ORF2) MSIHIEEEGPADAAKAPPFDYLQALHSALAHENDPVKRKQIEAGMVFKWLREEPLPFLSQLRR EKPIFSIPAITLVTRYNDVVEVLNANDVFSVDNIAPKLVENVGQNILAMNDSPKYEHEKSLLR LAFPRADLPRYRQIVVDEANRLLAKVGVDKPFDLTGDYALRVPAGAMARYLGVGEIPTEKVVA WTHALFNEIFLNPTNDPTAVAAAPAARQEALPMIDAIVAARKKQLAKSPPPEQPSVLDRYLVM 5 QSVPETYESDEGIRDVILGLLMGCVDLSGGAIVNALVELMKRPRVLRDALNVVNVEDDAAITG YVLEALRFRPPSTGVTSLCVRDYTVGRGTRHEEKVPAGALVMACSASAMHDHEHIDAPDQFRP GRLPSRNYLFWESGIHTCHGKYVAILHISLAIKQLLPAGVPSAIDPMPRVHGYPAPFRVRLAA AEG WO 00/22139 PCT/US99/23535 227 SEQ ID No 112 (Contig 12 >ORF3) MREPSSTPNWRNFGSNLPAGSDSVPPGEGFPIKKILALNLGKWKDTAGLQIAQALHLFEYGYK RYREGKFVLRATSDLGLGAIFESIDNWESFDQFEEFFKPWTFIRKPLVATRWAEDAEFGRQRL VGINPAHIRPATPADLADFVSGAEPKPIAIADGRTLEEVREGGQLYFLDYRIFKDIVDTDVQE ELGKYPLAPTCMLHQTAAGELLPVAIRLVHSRPGKGAHPDKIFTPSGPSDDWLTAKIAVASAD AIYQGQVTHLLYAHLIVEPFAVSTYRNLPATHPLHQLLRPHFFNTLAINELARRRFLGRGRFF DITSSVATMGSFELLTRAYTGKGIKGYGGKPWRFYESALPRDLSARDVRDLVGYHYRDDALLH WDAIQEYVGQVLKIAYPTPGSLSSDASLQRWIHELVSPQLGGMDSLLPPERADQLEKLTSLDD LIAIVTNIIFTATAYHAAVNFGQTDYYTWIPNAQFATYRSYGDVLNGSEKRQFKPLERLPGRA QSIRQMVLSRSLSMGPPLTSESLMTMKCLLQDPAAKQAFARYRERLAHIEREITERNRAREQP YLYLLPSMVPQSVAI SEQ ID No 113 (Contig 12 >ORF4) VSSSRSTGRVPRDRASPAGSCAPALVPGPPLSYASVMPPLDLHVALFGASGAGKTVLLAAFYR AQTQPSFQQEYAYKIQAVNKAQGNQLLGRFYRLEEGRFPDGSTRFDEYEFDFFPRDLPEPAVR IHWYDYPGRWWEDEPVDADEREAMRQGLIRLGMSQVGILLADGAKYRAEGTGYIRWLFEHFAD ECDRLRRASAATGDEVSFPREWILALSKADLCPPDYSARDFEREVCRDADDQLAKLCSVLRAE HAFGHRFMLLSSVAAPAGAQVDPRTSLGVRTLAPAILVSTVEGAVREAQAARKEKSAGETFFQ GLRDLVQFVDSLDDFLPKRYQIVSKILRFISIKDFATTRLDRLKKMREDAIRKGDTFTAVLTA MVAALRDDEGARAYHQNQ SEQ ID No 114 (Contig 12 >ORF5) MPAPAPLVETSRLLWRTRGEHWDYEFICVPEIPALPAWLSTLEAMLADADAGAGELRYGLLEI DDRGQRAPRAYPYVAVRFLDPARRDWTGRQVQHFAAWFPPVPPEAVAELPEAVPADWHLRVLD GLAGTYGSGEVFGLPEATIRAWKRSHDESRAARAMAIVKATPPVSLGGGEAAPSRWTRVPTLK KKPPEPPAAAGLLSVGAVPSGQGRRFGCFAIGAMMLAAFCRLMLACGVRLLGA SEQ TD No 115 (Contig 12 >ORF6) VRFRSSLGPLLLAALGAALTVSAAPRSAEASVFDSASRWPEDADGHVRIPVCIDPTSSAEQRV DGAAGGLIHAPNPSLADVITRVRTALQGSWERWSSVRFTGWESCDSLLPATRMTYVGVRIHPD WO 00/22139 PCT/US99/23535 228 APNQSDSIGVYNKGGSVQFKPWGADFNRCIKYNWQTARVEYSFDCVEQYAIHEMGHAIGFMHE WHHPLVPSACSQREPLPASDVASGWPSSRRYIVVNPGFYDYDSIMTYWSGCSDQDGVRFGSET LDAVDIQAVATVYPPVGGAPDVCNPGWFAGKRWFCAAQPTVSVGNSCSSGWVECLPHCNPRPF QGEWWTCPTNPYAVTGQSCSARWELCGD 5 SEQ ID No 116 (Contig 12 >ORF7) VGESQGALVGGNALSTNALNLNALNLNALNLNALNLSGLSARNLAAIQDPGPSGALARDFLRY AASCALSSTASFDFSWTDSNGKRHDERYPGLLGVAPAWASGPLDDAGQRIVSSCVAARVNYYQ VPVLLSARSLRDPLKTLSSSQELIDYPDVEGAFWGNLFAAQPYINACYNSATVDNSRAYQRDC 0 AAGHVTSGGQIVECGLIRIAGSCDRVCQKLNGAGQYYPSCVDRPGQSTATTKDVITTALP SEQ ID No 117 (Contig 12 >ORF8) VLAAHCERGGLTARAASLLARGAELAAARRAYLDAEGCYGRVEALLGALLPEERPARGLARFR LGRHTEALADLAAAREAAAAASEAGAEIELLLDEAMILDWTGEYRAARERVAAAERLAGRVAS 5 PLLGARLLLGVGRSLHRADREDEAAAVLTRAAAQAARLGDEGHETHIIALLLLGFILASLGRV EEAARDLDAVILSCEERSDLMHLGAALNNRGLARALQGDRAGMIADFERTIALGRELGQPAFE LVGRYNLAEYLYLMDDLAAARPHAPAVQAIAPRCGDRHAPVVVTLLIARLRLYQGDEAGARRI ALRLRAARDDAGCEALKPSEDVLCAMIELATRDDDRAAWAALEERSARCSVGQERIEVLEARA LAALRRGRRADARAQLERALAAASTIPTVMGGRLRRWYAELTRATESDAPDIDLAAAEATFTG 0 ARAREKVEY SEQ ID No 118 (Contig 12 >ORF9) QAYPDLWAERGRQELWLRQLPPRACAQLAREALGDAADGALIDRLVTQSEGQPFFLEELI RAT AEGRGDALPETVVAMVQVRLEALAPPARRILRAASVLGEVFWRGAVAHLLGGDEAAPLAEHLS 5 ALVAGELCVRHREGRFPGEEEYSFRQALLREGAYAQLTKDDRALGHRLAADWLEAAGEADPLV LAAHCERGGLTARAASLLARGAELAAARRAYLDAEGCYGRVEALLGALLPEERRARGLARFRL GRHTEALADLAAAREAAAAASEAGAEIELLLDEAMILDWTGEYRAARERVAAAERLAGRVASP LLGARLLLGVGRSLHPADREDEAAAVLTRAAAQAARLGDEGHETHIIALLLLGFILASLGRVE EAARDLDAVILSCEERSDLMHLGAALNNRGLARALQGDRAGMIADFERTIALGRELGQPAFEL 0 VGRYNLAEYLYLMDDLAAARPHARAVQAIAPRCGDRHAPVVVTLLIARLRLYQGDEAGARRIA WO 00/22139 PCT/US99/23535 229 LRLRAARDDAGCEALKPSEDVLCAMIELATRDDDRAAWAALEERSARCSVGQERIEVLEARAL AALRRGRRADARAQLERALAAASTIPTVMGGRLRRWYAELTRATESDAPDIDLAAAEATFTGA RAREKVEY 5

14. DNA sequence according to any of claims 1 to 5 wherein the DNA is selected from the group consisting of (a) the following DNA sequences: 0 Seq ID No 119 (>Contigl7) TTACGTTACTCATCCTATCTCGGCACCCTGTGTCGGTGATGTCGCTCGCC TCGAGCGCGAGCGGGACGACGTCGGCGCCGCGCTCGGTGAGCGCCGCCGC GAGGGCGCTCGCGAGATCGCTGGCGACGCCGGCCGGGGCCACGACGAGCC ACGTCCCCGCGACGTCGCCGCGTGACGCGGCGCTCACGGGTCTCCATTCG 5 ACGCGGTAGCGCCACGCGCCCACGGTGCTCTGCTCTCGGCGGCTCCGCCG CCACGCCGACAGGGCCGGCATGAGGCTCTCGAGGGCCGAGCGCCGCCCGC TGTCGGCGACGTGGAGCGCGTCCGAGAGCGCCGCGACGTCGCCGCGCTCG ATGGCTCGCCAGAACGCGGTCTCCTCGGCGGACGCTCCCGGCGCCGCGTC CTCATCGTCCGACGCGTCGCCTGCGTCGAGCCAGAACCGCTCGCGCTGGA 0 ACGCGTACGTCGGCAACGTCACGCGGCGCGCCCCGAGCGGAGCGAAGAAC GCACCCCAGTCGATGGCGTGCCCGCGCGCGTGGAGCTCGCCTGCCGAGAG GAGGAAGCGCTCGAGGTCGCCTTCGTCGCGGCGGAGCGAGGACACCACGG TCGCATCGCCGTCGATCGACGAGAGCGTCTCGTCGAGCGCGACGGTGAGC ACGGGGTGAGGGCTGACCTCGACGAAGAAGCGGTGGCCGTCGTCGAGCAG 5 GGCGCGCGTGGCGTGCTCGAAGCGGACGGTGTGGCGCAGGTTTCGGTACC AGTGGGCGGCGCCGAGGGCCTCGCCATCAAGCCTCTCGCCCGTCACCGCG GA3TAGAGCGGCACGGTCGCCGGGCGCGGCGCGATGCCGTCGAGCGCCTC CAGCATCGTCCGCTCGATGGCCTCCACGTGGGCGGAGTGGGAGGCGTACT CGACGCGGACCTTGCGGGCGAACAGCTGCGCCCCGCTCAGCTCTGCGACG 0 AGCTCGTCGATAGCGCCGGGGTCTCCGGAGACGAGGGCCGCGTGAGGGCT WO 00/22139 PCT/US99/23535 230 GTTGATCGCCGCTATCGCCAGGCGTTCGCCCAAGGGCGCAAGGCGCGCCT CGAGCTCGGCGGTGGTGAGCTCGACGGCGGACATGGCGCCGCGTCCCGCG AGCTTCGTAATGGCGCGCGAGCGGAGCGCGACGACCCTGGCGGCGTCTTC TAGCGAGAGCGCGCCCGCGACGTACGCGGCCGCGATCTCGCCCTGGCTGT GGCCGACGACCGCGTCGGGCGTGACTCCGGCGGCGCGCCAGGTGGCGGCG AGGGCGATCATGACGGCGAACAGCACGGGCTGCACCACGTCGACGCGCTC GAGCATGGGCGCGGCGTGCGCTTCGTCGCCGCCGAGCACGGCGAGGAGCG ACCAGTCGACGTGCGGCGCCAGGGCGCGCTCGCACGCCTCGATCTCGGCC CGAAAGGCGGGCGAGGAGGCGAGCAGAGCGCGCGCCATCGATGGCCACTG CGAGCCCTGGCCGGGGAAGACGAAGGCGACCTTGCCCGGCGGGAGCGCCT CGCCCGCGACCGTTCCTGCCCCCGCGCGCCCCTCGGCGAGCGCCGCGAGC GCCGAGAGCAGCGCGGCGCGATCGTCTGCCACGACGGCGGCGCGACGCTC GAAATGCGACCGCGTGGTCGCGAGCGACGCCGCGACGTCGACGAGGGCGA CGTCCTCGTGCTCGGCGAGGTGCGCGTGGAGCTTGCCCGCCTGAGCGCGG AGCGCCGCGTCGCTCTTCGCCGAGAGGAGCACCGGCACCGGCGGCGCGAA GGGCGCGCGGGCGGGCTCCCCGGCCTGGTCGTCGCCGGCCGCCGCGCGCG GCGCTTCCTCGAGGACCACGTGCGCGTTGGTGCCGGAGATCCCGAACGAC GACACCGCCGCGCGCCGAGGAGACCCGCCTGGCTTCCACGGTACCTCCTC GGTCAAGAGGCGGATCGCGCCGGACGACCAATCGATGTGCTGCGACGGGC TCGCGGCGTGGAGCGTCCTCGGGAGGACGCCGCTCTGCAGCGCGAGCACC ATCTTGATGACGCCGCCGATCCCCGCGGCGGCCTGCGTGTGCCCGAGGTT CGACTTTAGGCTCCCGAGCCACAGCGGGCGCTCCTTCGCGTGCGCCGCGC CGTACGTCGCGAAGAGCGCGCGCGCCTCGATGGGATCGCCGAGCGTCGTG CCGGTTCCGTGCGCCTCGACGGCGTCGACGTCCGCGGGGGCGAGCCCCGC GCTCGCGAGCGCGTCCCGGATCACGCGCTCTTGCGCGGGGCCGTTCGGCG CCGTGAGCCCTTGGCTCTTGCCGTCCTGGTTGACGGCCGATCCGCGCACG ATCGCGAGCACGGGGTGCCCGTTCTTCCGGGCGTCCGACAGGCGCTCGAG GAGCACTATCCCAGCGCCTTCCGACCAGCCCGCGCCGTTCGCGTGCGACG AGAACGACTTGCACCGCCCGTCCGGCGCGCCCGCGTGCTGCGCGCTGAAC TCGCCGAAGATCCCGGGGGTCGCCATCACGGTCACGCCGCCGGCGAGCGC WO 00/22139 PCTIUS99/23535 231 GAGCGAGCACTCGCCTCGACGGATGr-GCGTGGCAGGCGAGGTGGAGCGCGA CGAGCGACGAGCTGCACGCCGTGTCGACGCT Seq ID No 120 (>Contigl8) TTTTAGGANCCCCGACGTGCACGATCGGCTCGCCAACCTCGTGGCGCGCC GGGACTATTTTTACCAGCTCGCGTTGCGCGCCGCGGGGACCTACGTGCGG GGCCTCGTCCGCGCCCCGCACGACGGCGCGCGCCCCCCCGCGTTCGCGCC GCGTGGGGCGGCGCTCGTCACGGGCGGGACCGGGGCGCTCGGGGCGCACG TTGCCCGTTGGTTCGCGCGGATCGGCGCCGAGCACATCGTGCTCGCGAGC CGCCGCGGAGCCGCGGCCCCCGGCGC GGCCGCGCTCGCCGAGGAGCTTTC GGTGCTCGGCGCGCGCGTGACGCTGC",-TTGCGTGCGACGTCCCCGATCGTG AGGCGGTCGCGGGGCTCGTGCGCAACG-TCAGGCCGGCGGAGCGACGGTG CGCGCCGTGTTCCACGCGGGCGGTGCGATGCACGAGGCGCCGGTCGCCGC CAGGGTAGGTGCAGCACCGGAGCGGC CGCAGCACCTCCAAGACGTCTTCGCGCAGCGCCCGCTCAACGCGTTTGTC CTCTTCTCGTCAGAAACGGGTGTGTGGGGCGGTGGCCGGCAAGGCGCGTA CGCCGCGGCGAACGCGTTCCTCGACGCGCTCGCCGAGGCGCGTCGCGCGG ACGGCCTCGCGGCGACCTCGATCGCGTGGGGCGCGTGGGCGGGCGGCGGA ATGCTCGCGACCGACGCCGAGCGGCGC'TTGAAGCATCGCGGCGTCGCGCC GATGGATCCGGAGCTCGCCGTCGCGG -CCCTCGCGCACGCGCTCGATCACG CCGAGACGTGCCTCGCCGTCGCTGACGTCGACTGGGCGCGCTTCGCCCCG TCGTTCGCCTCGGCGCGTCCTCGCCCGCTCCTCGACGAGCTCGCGGAGGC GCGATCGGCGCTCGACGCGCTGCGCGAGCCACCGGACGACGCGCGCACGG CCGCCGGTCCCGAGCCCGCAAGCACGCTGAGGACCACGCTCGCGGCGCTC CCGGAGGGCGAGCGCCACCGCCACOTCCTCGCGCTCGTGCGGACGGAGAC GGCGGCGGTGCTCGGGCACGCGGACG-CGTCGCGCGTCGAGCCGAACCGCG GGTTCTTTGACCTCGGGCTCGACT, -CCATGTCCGTCGAGCTCCGCAGG CGCGTCCAGCGCGOGACCGGCATCAAGCTCCCGGCGACGCTCGCGTTCGA CCACCCGACGCCGAGCGCGCTCGCGAGCAAGGI-TGCTCGCCGCGATCGTCC TCCACGACGCGACCCCGCGCGCCTCG- -CCCGCCGCGGAGCTCGAGCGCCTC WO 00/22139 PCT/US99/23535 232 GAGGGGATGCTCTCGGCGATCTACGC-GGACGAAGCGCTCCGCGACGACCT CACGGCGCGCCTCCGCGCCTTCCTGGACAGCGCGCGGTCCGCACCGAAC GCCCCGACGACGCCGCGTTCGCCGAG 7AGCTCGGCTCCGCGAGCGCCGAC GAACTCATTCGCCTGATCGATCAGAAGCTCGGAGATCGCATCGATGTCGA CCGTTACTAACGACACGCTCACGGAGTACTTGCGGCGCCTCACTCAAGAG CTCCACAGGAGCGAGACGCGCCTGCGTGCGACGGAAGAGAGGCGACATGA GCCGATCGCCATCGTCGGCCTCGGGCTCCCCTTCCGGGGCGGGATCCACG ACCGCGACACGCTCTGGACGTTCCrnC-GAGGAGGGCCGCGACGCCATCGCG CCGATCCTCGCGAGCCGCTk-GGACGC- -GGACGCGACGTACGACCTCGATCC GGACGCCGTCGGCAAGAGCTACGT.GC7-GCGACGCCGCCATGCTCGATCGCG TCGACCTTTTCGACGCCGATTTC',TTCGGGATCAGCCCGCGCGAGGCGAAG TACGTCGACCCGCAGCACCGCCTCT TGCTCGAGACGTCGTGGCAAGCGCT CGAGGACGCGGGGATTGTGCCGGCGT-'.CGCTGCGAGACTCGAAGACCGGCG TCTTCGTCGGCACGGGCGCGAGCGACTACGCGTTCCTCCAGAGCGATCGC GACGCCTCGGAGGCGTACGCGTTCATGGGGATGATCTCGTCGTTCGCGGC GGGCCGCCTCGCGTTCACGCTCGGGC -TCCAAGGCCCCGCGCTATCGATCG ACAC'"GOGTGCTCTTCGTCGCTCGT-CGCGCTCCACCTCGCGTGCCAGTCG CTGCGTCAAGGCGAGTGCGACCTCGCGCTCGTCGCGGGTGTGCAGGTCAT GTCGTCGCCGGAGGTGTTCGTGCTGO'7TCTCGCGCACGCGCGCGCTCGCGA GCA-GGGTGAAGTTCGGAGCAGCAGCG GGCGAAGGCGTCGTCGTCCTGGCCG ':TCGAGCGCCTCCGCGACGCGCGCGC GAAAGGGCGCCCGATCCTCGCGGTLGATCCGCGGCAGCGCGGTGAACCACG ACGGC-ACGTCGAGCGGGATCACGGO:CCGACGGGCCCGCGCAGCAGAAG GTC-TCCGCGCCGCGCTCGACGACGO-GCGGCTTGTCCCCGCCGAOGTCGA CGTCG---TCGAGTGCCACGGCACGGGGAC -CTCCATCGGCGATCCCATCGAAG TGPAA-CGCTCGCCGCCGTCTACGGC-GAGGGGCGCCCCAAGGACCGCCCG CTG:T7CCTGGGCGCGCTGAAGACCAACATCGGGCACCTCGAGTTCGCGTC GGC-CTCGCCGGCGTCGCGAAGATGr-GTCGCCTCCATGCGCCACGCGACCC TCCCCr-GCGACGCTGCACACGAGCO C"-GCTCAACCCGCTCGTCGACTGGGAC GCGC-TCCCCGTGCGCGTCGTCGACGC -CGCGCGCCCGTGGACGCGCCGCGA WO 00/22139 PCTIUS99/23535 233 CGACGGCGCCCCCCGGCGCGCCGGCGTCACGGCGATCGTCGAGGAGGCGC CCGCCGAGCCCGAGCCCACGACGCCCGACGCCGCGCCCGCGCTTCCGGCC GTGCCCGTTCTCCTCTCGGGCAAGACCGACGAGGCGCTGCGCGCGCAGGC AGCGCGCCTCCACGCGCACCTCGCGGGGCGCCCCGACGCGCGGCTCGTCG ACATCGCCGCGTCGCTCGCGACGACGCGCACGCACTTCGATCGACGCGCG GCCGTCGTCGCGGCGGATCGCGACGAGCTCCTCGGCGCGCTCGACGCGCT CGCGCGCGGCGAGGCAGGCCCGGGGTCGGTCGTCGCGAGCGCGATCCCCG CCGGCAGGGTCGTGTTCGTGTTCCCCGGCCAAGGCTCGCAGTGGGTCGGG ATGGCGCGCGCGCTCCTCGCGTCGTCGGTGGTCTTCCGCGACGAGATCGC GGCCTGCGAGCGCGCGCTCGCGCCGCACGTCGCCTGGTCGCTCGGCGCCG TTCTCCGGGGCGACGGCGACGAGGCGACGCTCCTCGGCCGCGTCGACGTC GTGCAGCCGGTCCTCTTCGCCGTCATGGTCGCCCTCGCCGCGCTCTGGCG CTCGATCGGCGTCACGCCCGACGCCGTCGTCGGGCACAGCCAAGGCGAGA TCGCCGCCGCCTACGTCGCCGGCGCCCTCTCGCTCGAAGACGCCGCCAAG GTCGTCGCGCTGCGCGCACGAGCGCTCACGAAGATCGCGGGGCGCGGGGC GATGGCCGCCGTCGAGCTCGGCGCACGCGACACCGAGGCGCGCCTCGCGC CGTTCGGCGACGCCATCGCGATCGCGGCGATCAACAGCCCGCGCGCCACG CTCGTCGCGGGCGACACGGACGCGATCGACGCGCTCGTCCGCGACCTCGA GGCCGCGCAGATCTTCGCGCGGAAGGTGCGTGTCGACTACGCGTCGCACT CGGCGCACGTCGAGGCGATCGAGCGCGAGCTCCTCGCGGATCTCGCGGGG ATCGAACCGCGCGCGGGCGCTGTGCCGCTTTACTCCGCGGTGACGGGCGC GAAGCTCGACGGGAACCGCCTCGACCCCGCGCATTGGTTCCGGAACCTGC GCTCGACAAAAAACTTTGAGGACGCCACGCGCGCGCTCCACGACGACGGC CGCCGGGTATCCTCATNATCNNGGGCGTNCAGAGGAGTCGGTATTNCCCC CCCCCGCCTTNCCCG, or their complementary strands, WO 00/22139 PCTIUS99/23535 234 (b) DNA-sequences which hybridise under stringent conditions to regions of DNA-sequences according to (a) encoding proteins or to fragments of said DNA-sequences, (c) DNA-sequences which hybridise to the DNA-sequences accord ing to (a) and (b) because of a degeneration of the genetic code, (d) allele variations and mutants resulting by substitution, insertion or deletion of nucleotides or inversion of nucleotide segments of DNA-sequences according to (a) to (c) , wherein the variations and mutants offer isofunctional expression products.

15. Peptide encoded by a DNA sequence according to claim 14 selected from the group consisting of Seq ID No 121 >Contig17_001 828 amino acids MW=86259 D pI=5.60 numambig=1 MTVMATPGIFGEFSAQHAGAPDGRCKSFSSHANGAGWSEGAGIVLLERLSDARKNGHPVL AIVRGSAVNQDGKSQGLTAPNGPAQERVIRDALASAGLAPADVDAVEAHGTGTTLGDPIE ARALFATYGAAHAKERPLWLGSLKSNLGHTQAAAGIGGVIKMVLALQSGVLPRTLHAASP SQHIDWSSGAIRLLTEEVPWKPGGSPRRAAVSSFGISGTNAHVVLEEAPRAAAGDDQAGE PARAPFAPPVPVLLSAKSDAALRAQAGKLHAHLAEHEDVALVDVAASLATTRSHFERRAA VVADDRAALLSALAALAEGRAGAGTVAGEALPPGKVAFVFPGQGSQWPSMARALLASSPA FRAEIEACERALAPHVDWSLLAVLGGDEAHAAPMLERVDVVQPVLFAVMIALAATWRAAG VTPDAVVGHSQGEIAAAYVAGALSLEDAARVVALRSRAITKLAGRGAMSAVELTTAELEA RLAPLGERLAIAAINSPHAALVSGDPGAIDELVAELSGAQLFARKVRVEYASHSAHVEAI ERTMLEALDGIAPRPATVPLYSAVTGERLDGEALGAAHWYRNLRHTVRFEHATRALLDDG HRFFVEVSPHPVLTVALDETLSSIDGDATVVSSLRRDEGDLERFLLSAGELHARGHAIDW GAFFAPLGARRVTLPTYAFQRERFWLDAGDASDDEDAAPGASAEETAFWRAIERGDVAAL WO 00/22139 PCT/US99/23535 235 SDALHVADSGRRSALESLMPALSAWRRSRREQSTVGAWRYRVEWRPVSAASRGDVAGTWL VVAPAGVASDLASALAAALTERGADVVPLALEASDITDTGCRDRMSNVX Seq ID No 122 >Contigl8_002 502 amino acids MW=53019 D pI=6.83 numambig=1 FRXPDVHDRLANLVARRDYFYQLALRAAGTYVRGLVRAPHDGARPPAFAPRGAALVTGGT GALGAHVARWFARIGAEHIVLASRRGAAAPGAAALAEELSVLGARVTLVACDVPDREAVA GLVRNVKAGGATVPAVFHAGGAMHEAPVAAMRVEELADAIAVKARGAQHLQDVFAQRPLN AFVLFSSETGVWGGGRQGAYAAANAFLDALAEARRADGLAATSIAWGAWAGGGMLATDAE RRLKHRGVAPMDPELAVAALAHALDHAETCLAVADVDWARFAPSFASARPRPLLDELAEA RSALDALREPPDDARTAAGPEPASTLRTTLAALPEGERHRHLLALVRTETAAVLGHADAS RVEPNRGFFDLGLDSLMSVELRRRVQRATGIKLPATLAFDHPTPSALASKVLAAIVLHDA TPRASPAAELERLEGMLSAIYADEALRDDLTARLPAFLDKRAVRTERPDDAAFAEKLGSA SADELIRLIDQKLGDRIDVDRY* Seq ID No 123 >Contigl8_010 840 amino acids MW=88062 D pI=5.74 numambig=6 MSTVTNDTLTEYLRRLTQELHRSETRLRATEERRHEPIAIVGLGLPFRGGIHDRDTLWTF LEEGRDAIAPILASRWNADATYDLDPDAVGKSYVRDAAMLDRVDLFDADFFGISPREAKY VDPQHRLLLETSWQALEDAGIVPASLRDSKTGVFVGTGASDYAFLQSDRDASEAYAFMGM ISSFAAGRLAFTLGLQGPALSIDTACSSSLVALHLACQSLRQGECDLALVAGVQVMSSPE VFVLLSRTRALASDGRSKTFSANADGYGRGEGVVVLAVERLRDARAKGRPILAVIRGSAV NHDGTSSGITVPNGPAQQKVLRAALDDARLVPADVDVVECHGTGTSIGDPIEVNALAAVY GEGRPKDRPLFLGALKTNIGHLEFASGLAGVAKMVASMRHATLPATLHTSPLNPLVDWDA LPVRVVDAARPWTRRDDGAPRRAGVTAIVEEAPAEPEPTTPDAAPALPAVPVLLSGKTDE ALRAQAARLHAHLAGRPDARLVDIAASLATTRTHFDRRAAVVAADRDELLGALDALARGE AGPGSVVASAIPAGRVVFVFPGQGSQWVGMARALLASSVVFRDEIAACERALAPHVAWSL GAVLRGDGDEATLLGRVDVVQPVLFAVMVALAALWRSIGVTPDAVVGHSQGEIAAAYVAG ALSLEDAAKVVALPARALTKIAGRGAMAAVELGARDTEARLAPFGDAIAIAAINSPRATL VAGDTDAIDALVRDLEAAQIFARKVRVDYASHSAHVEAIERELLADLAGIEPRAGAVPLY WO 00/22139 PCT/US99/23535 236 SAVTGAKLDGNRLDPAHWFRNLRSTKNFEDATRALHDDGRRVSSXSXAXRGVGIXPPRLX X

16. Recombinant expression vector which comprises a DNA sequence according to any of claims 1 to 10, 12 and 14.

17. Procaryotic or eucaryotic cell which has been transfected or transformed with a DNA-sequence according to any of claims 1 to 10, 12 and 14 or with a recombinant expression vector ac cording to claim 16.

18. Cell according to claim 17, wherein the cell is derived from myxobacteria.

19. Cell according to claim 17, wherein the cell is derived from a Sorangium strain.

20. Cell according to claim 17, wherein the cell is derived from Sorangium cellulosum.

21. Cell according to claim 17, wherein the cell is derived from a Streptomyces strain.

22. Cell according to claim 17, wherein the cell is derived from Escherichia coli.

23 . Process for an enzymatic biosynthesis, mutasynthesis or partial synthesis of polyketide or heteropolyketide compounds, wherein a cell according to any of claims 17 to 22 is culti- WO 00/22139 PCT/US99/23535 237 vated in a suitable culture medium and the polyketide or het eropolyketide compound is isolated from the medium.

24. Process according to claim 23, wherein the polyketide or heteropolyketide compound is an epothilone.