DK2450379T3

DK2450379T3 - Humane bindingsmolekyler, der er i stand til at neutralisere influenzavirus h5n1, og anvendelser deraf

Info

Publication number: DK2450379T3
Application number: DK12153013.3T
Authority: DK
Inventors: Den Brink Edward Norbert Van; Kruif Cornelis Adriaan De; Mark Throsby
Original assignee: Crucell Holland Bv
Priority date: 2006-09-07
Filing date: 2007-09-06
Publication date: 2016-02-08
Also published as: BRPI0716983B8; EP2455399A3; EP2455399B1; MX343198B; BRPI0716983B1; SG174773A1; EP2455398A2; DK2455399T3; EP2450379B1; RS52688B; EP2455399A2; EP2450376A2; EP2450376B1; EP2455398A3; EP2450376A3; EP2455398B1; NZ574581A; MY165458A; BRPI0716983A2; SG10201607410TA

Description

DESCRIPTION

FIELD OF THE INVENTION

[0001] The invention relates to medicine. In particular, the invention relates to the diagnosis, prophylaxis and/or treatment of an infection by influenza virus H5N1.

BACKGROUND OF THE INVENTION

[0002] Influenza viruses consist of three types, A, B and C. Influenza A viruses infect a wide variety of birds and mammals, including humans, horses, marine mammals, pigs, ferrets, and chickens. In animals most influenza A viruses cause mild localized infections of the respiratory and intestinal tract. However, highly pathogenic influenza A strains such as H5N1 exist that cause systemic infections in poultry in which mortality may reach 100%. Animals infected with influenza A often act as a reservoir for the influenza viruses and certain subtypes have been shown to cross the species barrier to humans.

[0003] Influenza A viruses can be classified into subtypes based on allelic variations in antigenic regions of two genes that encode surface glycoproteins, namely, hemagglutinin (HA) and neuraminidase (NA) which are required for viral attachment and cellular release. Other major viral proteins include the nucleoprotein, the nucleocapsid structural protein, membrane proteins (M1 and M2), polymerases (PA, PB and PB2) and non-structural proteins (NS1 and NS2).

[0004] Currently, sixteen subtypes of HA (H1-H16) and nine ΝΑ (N1-N9) antigenic variants are known in influenza A virus. Previously, only three subtypes have been known to circulate in humans (H1N1, H1N2, and H3N2). However, in recent years, the pathogenic H5N1 subtype of avian influenza A has been reported to cross the species barrier and infect humans as documented in Hong Kong in 1997 and 2003, leading to the death of several patients.

[0005] In humans, the avian influenza virus infects cells of the respiratory tract as well as the intestinal tract, liver, spleen, kidneys and other organs. Symptoms of avian influenza infection include fever, respiratory difficulties including shortness of breath and cough, lymphopenia, diarrhea and difficulties regulating blood sugar levels. In contrast to seasonal influenza the group most at risk are healthy adults which make up the bulk of the population.Due to the high pathogenicity of certain avian influenza A subtypes, particularly H5N1, and their demonstrated ability to cross over to infect humans, there is a significant economic and public health risk associated with these viral strains, including a real epidemic and pandemic threat. The scale of the threat is illustrated by the 1918 influenza pandemic which killed over 50 million people.

[0006] Currently, no effective vaccines for H5N1 infection are available, so passive immunotherapy with immunoglobulins may be an alternative strategy. Use of passive immunization during the 1918 pandemic reportedly halved the death rate. In view of their therapeutic benefit in humans, there is thus a need for binding molecules, preferably human binding molecules, capable of neutralizing H5N1. The present invention provides these binding molecules and shows that they can be used in medicine, in particular for diagnosis, prevention and/or treatment of H5N1 infections.

DESCRIPTION OF THE FIGURES

[0007]

In Fig 1 immunoblot analysis of different hemagglutinins (HAs) using antibodies CR6307 (left part), CR6323 (middle part) and CR5111 (right part) is presented. Recombinant HAs were subjected to reducing SDS-PAGE analysis and immunoblot analysis. In lanes 1 sHAof H5N1TV is shown; in lanes 2 recombinant HA, subtype H5 (A/Vietnam/1203/2004 (H5N1)) is shown; in lanes 3 recombinant HA, subtype H3 (A/Wyoming/3/2003(H3N2)) is shown; and in lanes 4 recombinant HA, subtype H1 (A/New Caledonia/20/99 (H1N1)) is shown. The position where HAO, HA1 and HA2 can be found is also indicated.

Fig 2 shows the average clinical score per group of mice in a study (example 12) wherein, one day before infection with influenza H5N1 virus, mice were prophylactically treated with three human H5N1 monoclonal antibodies CR6261, CR6323, and CR6325, in different doses.

Fig 3 shows the change in body weight during the prophylactic treatment of mice with anti-H5N1 antibodies during 21 days post infection (example 12).

Fig 4 shows the number of surviving mice in the different groups in the study of Fig 2 and 3 (example 12).

Fig 5 shows the mortality rate in relation to the dose given of the anti-H5N1 antibodies in the study of Figs 2-4 (example 12).

Fig 6 shows the average clinical score per group of mice in a study (example 13) wherein mice were infected with a lethal dose of H5N1 influenza virus and treated at different time points after infection (4 hr, 1,2 and 3 days) with CR6261 anti-FI5N1 monoclonal antibody, or a non-related antibody CR2006 (administered at day 1 post-infection).

Fig 7 shows the number of surviving animals in each group of the study described in fig 6. All animals of group 1-4, except for one animal in group 1 survived the entire study up to day 21 post-infection. All animals of group 5 had died at day 9.

Fig 8 shows the average body weight of the mice in each group during the study as described for fig 6. Measuring the body weight of the mice in group 5 stopped at day 9 as all mice in that group had died by that time. All remaining mice in groups 1-4 reached normal levels of body weight at day 21 post-infection, although it depended on the time of treatment how fast each group recovered.

Fig 9 shows the percentage of surviving animals in each group of a study wherein mice were infected with a lethal dose of H1N1 influenza virus and treated at different time points (1 day prior-, 1, 2 and 3 days post-infection) with CR6261 anti-FI5N1 monoclonal antibody, or a non-related antibody CR57 (administered at day 1 post-infection).

Fig 10 shows the average body weight of the mice in each group during the study as described for fig 9. Measuring the body weight of the mice in group 5 stopped at day 9 as all mice in that group had died by that time. All remaining mice in groups 1-4 reached normal levels of body weight at day 21 post-infection, although it depended on the time of treatment how fast each group recovered.

DESCRIPTION OF THE INVENTION

[0008] Here below follow definitions of terms as used in the invention.

[0009] As used herein the term "binding molecule" refers to an intact immunoglobulin including monoclonal antibodies, such as chimeric, humanized or human monoclonal antibodies, or to an antigen-binding and/or variable domain comprising fragment of an immunoglobulin that competes with the intact immunoglobulin for specific binding to the binding partner of the immunoglobulin, e g. H5N1. Regardless of structure, the antigen-binding fragment binds with the same antigen that is recognized by the intact immunoglobulin. An antigen-binding fragment can comprise a peptide or polypeptide comprising an amino acid sequence of at least 2, 5, 10, 15, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, or 250 contiguous amino acid residues of the amino acid sequence of the binding molecule.

[0010] The term "binding molecule", as used herein includes all immunoglobulin classes and subclasses known in the art. Depending on the amino acid sequence of the constant domain of their heavy chains, binding molecules can be divided into the five major classes of intact antibodies: IgA, IgD, IgE, IgG, and IgM, and several of these may be further divided into subclasses (isotypes), e.g., lgA1, lgA2, lgG1, lgG2, lgG3 and lgG4.

[0011] Antigen-binding fragments include, inter alia, Fab, F(ab'), F(ab')2, Fv, dAb, Fd, complementarity determining region (CDR) fragments, single-chain antibodies (scFv), bivalent single-chain antibodies, single-chain phage antibodies, diabodies, triabodies, tetrabodies, (poly)peptides that contain at least a fragment of an immunoglobulin that is sufficient to confer specific antigen binding to the (poly)peptide, etc. The above fragments may be produced synthetically or by enzymatic or chemical cleavage of intact immunoglobulins or they may be genetically engineered by recombinant DNA techniques. The methods of production are well known in the art and are described, for example, in Antibodies: A Laboratory Manual, Edited by: E. Harlow and D, Lane (1988), Cold Spring Harbor Laboratory, Cold Spring Harbor, New York. A binding molecule or antigen-binding fragment thereof may have one or more binding sites. If there is more than one binding site, the binding sites may be identical to one another or they may be different.

[0012] The binding molecule can be a naked or unconjugated binding molecule but can also be part of an immunoconjugate. A naked or unconjugated binding molecule is intended to refer to a binding molecule that is not conjugated, operatively linked or otherwise physically or functionally associated with an effector moiety or tag, such as inter alia a toxic substance, a radioactive substance, a liposome, an enzyme. It will be understood that naked or unconjugated binding molecules do not exclude binding molecules that have been stabilized, multimerized, humanized or in any other way manipulated, other than by the attachment of an effector moiety or tag. Accordingly, all post-translationally modified naked and unconjugated binding molecules are included herewith, including where the modifications are made in the natural binding molecule-producing cell environment, by a recombinant binding molecule-producing cell, and are introduced by the hand of man after initial binding molecule preparation. Of course, the term naked or unconjugated binding molecule does not exclude the ability of the binding molecule to form functional associations with effector cells and/or molecules after administration to the body, as some of such interactions are necessary in order to exert a biological effect. The lack of associated effector group or tag is therefore applied in definition to the naked or unconjugated binding molecule in vitro, not in vivo.

[0013] As used herein, the term "biological sample" encompasses a variety of sample types, including blood and other liquid samples of biological origin, solid tissue samples such as a biopsy specimen or tissue cultures, or cells derived there from and the progeny thereof The term also includes samples that have been manipulated in any way after their procurement, such as by treatment with reagents, solubilization, or enrichment for certain components, such as proteins or polynucleotides. The term encompasses various kinds of clinical samples obtained from any species, and also includes cells in culture, cell supernatants and cell lysates.

[0014] The term "complementarity determining regions" (CDR) as used herein means sequences within the variable regions of binding molecules, such as immunoglobulins, that usually contribute to a large extent to the antigen binding site which is complementary in shape and charge distribution to the epitope recognized on the antigen. The CDR regions can be specific for linear epitopes, discontinuous epitopes, or conformational epitopes of proteins or protein fragments, either as present on the protein in its native conformation or, in some cases, as present on the proteins as denatured, e.g., by solubilization in SDS. Epitopes may also consist of posttranslational modifications of proteins.

[0015] The term "deletion", as used herein, denotes a change in either amino acid or nucleotide sequence in which one or more amino acid or nucleotide residues, respectively, are absent as compared to the parent, often the naturally occurring, molecule.

[0016] The term "expression-regulating nucleic acid sequence" as used herein refers to polynucleotide sequences necessary for and/or affecting the expression of an operably linked coding sequence in a particular host organism. The expression-regulating nucleic acid sequences, such as inter alia appropriate transcription initiation, termination, promoter, enhancer sequences; repressor or activator sequences; efficient RNA processing signals such as splicing and polyadenylation signals; sequences that stabilize cytoplasmic mRNA; sequences that enhance translation efficiency (e.g., ribosome binding sites); sequences that enhance protein stability; and when desired, sequences that enhance protein secretion, can be any nucleic acid sequence showing activity in the host organism of choice and can be derived from genes encoding proteins, which are either homologous or heterologous to the host organism. The identification and employment of expression-regulating sequences is routine to the person skilled in the art.

[0017] The term "functional variant", as used herein, refers to a binding molecule that comprises a nucleotide and/or amino acid sequence that is altered by one or more nucleotides and/or amino acids compared to the nucleotide and/or amino acid sequences of the parental binding molecule and that is still capable of competing for binding to the binding partner, e.g. H5N1, with the parental binding molecule. In other words, the modifications in the amino acid and/or nucleotide sequence of the parental binding molecule do not significantly affect or alter the binding characteristics of the binding molecule encoded by the nucleotide sequence or containing the amino acid sequence, i.e. the binding molecule is still able to recognize and bind its target. The functional variant may have conservative sequence modifications including nucleotide and amino acid substitutions, additions and deletions. These modifications can be introduced by standard techniques known in the art, such as site-directed mutagenesis and random PCR-mediated mutagenesis, and may comprise natural as well as non-natural nucleotides and amino acids.

[0018] Conservative amino acid substitutions include the ones in which the amino acid residue is replaced wth an amino acid residue having similar structural or chemical properties. Families of amino acid residues having similar side chains have been defined in the art. These families include amino acids with basic side chains (e.g., lysine, arginine, histidine), acidic side chains (e.g., aspartic acid, glutamic acid), uncharged polar side chains (e.g., asparagine, glutamine, serine, threonine, tyrosine, cysteine, tryptophan), non-polar side chains (e.g., glycine, alanine, valine, leucine, isoleucine, proline, phenylalanine, methionine), beta-branched side chains (e.g., threonine, valine, isoleucine) and aromatic side chains (e.g., tyrosine, phenylalanine, tryptophan). It will be clear to the skilled artisan that other classifications of amino acid residue families than the one used above can also be employed. Furthermore, a variant may have non-conservative amino acid substitutions, e.g., replacement of an amino acid with an amino acid residue having different structural or chemical properties. Similar minor variations may also include amino acid deletions or insertions, or both. Guidance in determining which amino acid residues may be substituted, inserted, or deleted without abolishing immunological activity may be found using computer programs well known in the art.

[0019] A mutation in a nucleotide sequence can be a single alteration made at a locus (a point mutation), such as transition or transversion mutations, or alternatively, multiple nucleotides may be inserted, deleted or changed at a single locus. In addition, one or more alterations may be made at any number of loci within a nucleotide sequence. The mutations may be performed by any suitable method known in the art.

[0020] The term "host11, as used herein, is intended to refer to an organism or a cell into which a vector such as a cloning vector or an expression vector has been introduced. The organism or cell can be prokaryotic or eukaryotic. It should be understood that this term is intended to refer not only to the particular subject organism or cell but to the progeny of such an organism or cell as well. Because certain modifications may occur in succeeding generations due to either mutation or environmental influences, such progeny may not, in fact, be identical to the parent organism or cell, but are still included within the scope of the term "host" as used herein.

[0021] The term "human", wfien applied to binding molecules as defined herein, refers to molecules that are either directly derived from a human or based upon a human sequence. When a binding molecule is derived from or based on a human sequence and subsequently modified, it is still to be considered human as used throughout the specification. In other words, the term human, wfnen applied to binding molecules is intended to include binding molecules having variable and constant regions derived from human germline immunoglobulin sequences or based on variable or constant regions occurring in a human or human lymphocyte and modified in some form. Thus, the human binding molecules may include amino acid residues not encoded by human germline immunoglobulin sequences, comprise substitutions and/or deletions (e.g., mutations introduced by for instance random or site-specific mutagenesis in vitro or by somatic mutation in vivo). "Based on" as used herein refers to the situation that a nucleic acid sequence may be exactly copied from a template, or with minor mutations, such as by error-prone PCR methods, or synthetically made matching the template exactly or with minor modifications. Semi-synthetic molecules based on human sequences are also considered to be human as used herein.

[0022] The term "insertion", also known as the term "addition", denotes a change in an amino acid or nucleotide sequence resulting in the addition of one or more amino acid or nucleotide residues, respectively, as compared to the parent sequence.

[0023] The term "isolated", when applied to binding molecules as defined herein, refers to binding molecules that are substantially free of other proteins or polypeptides, particularly free of other binding molecules having different antigenic specificities, and are also substantially free of other cellular material and/or chemicals. For example, wfnen the binding molecules are recombinantly produced, they are preferably substantially free of culture medium, and wfnen the binding molecules are produced by chemical synthesis, they are preferably substantially free of chemical precursors or other chemicals, i.e., they are separated from chemical precursors or other chemicals which are involved in the synthesis of the protein. The term "isolated" when applied to nucleic acid molecules encoding binding molecules as defined herein, is intended to refer to nucleic acid molecules in which the nucleotide sequences encoding the binding molecules are free of other nucleotide sequences, particularly nucleotide sequences encoding binding molecules that bind binding partners other than H5N1. Furthermore, the term "isolated" refers to nucleic acid molecules that are substantially separated from other cellular components that naturally accompany the native nucleic acid molecule in its natural host, e.g., ribosomes, polymerases, or genomic sequences with which it is naturally associated. Moreover, "isolated" nucleic acid molecules, such as cDNA molecules, can be substantially free of other cellular material, or culture medium when produced by recombinant techniques, or substantially free of chemical precursors or other chemicals when chemically synthesized.

[0024] The term "monoclonal antibody" as used herein refers to a preparation of antibody molecules of single molecular composition. A monoclonal antibody displays a single binding specificity and affinity for a particular epitope. Accordingly, the term "human monoclonal antibody" refers to an antibody displaying a single binding specificity which has variable and constant regions derived from or based on human germline immunoglobulin sequences or derived from completely synthetic sequences. The method of preparing the monoclonal antibody is not relevant.

[0025] The term "naturally occurring" as used herein as applied to an object refers to the fact that an object can be found in nature. For example, a polypeptide or polynucleotide sequence that is present in an organism that can be isolated from a source in nature and which has not been intentionally modified by man in the laboratory is naturally occurring.

[0026] The term "nucleic acid molecule" as used in the present invention refers to a polymeric form of nucleotides and includes both sense and anti-sense strands of RNA, cDNA, genomic DNA, and synthetic forms and mixed polymers of the above. A nucleotide refers to a ribonucleotide, deoxynucleotide or a modified form of either type of nucleotide. The term also includes single- and double-stranded forms of DNA. In addition, a polynucleotide may include either or both naturally occurring and modified nucleotides linked together by naturally occurring and/or non-naturally occurring nucleotide linkages. The nucleic acid molecules may be modified chemically or biochemically or may contain non-natural or derivatized nucleotide bases, as will be readily appreciated by those of skill in the art. Such modifications include, for example, labels, methylation, substitution of one or more of the naturally occurring nucleotides with an analog, internucleotide modifications such as uncharged linkages (e.g., methyl phosphonates, phosphotriesters, phosphoramidates, carbamates, etc ), charged linkages (e.g., phosphorothioates, phosphorodithioates, etc.), pendent moieties (e.g., polypeptides), intercalators (e.g., acridine, psoralen, etc.), chelators, alkylators, and modified linkages (e.g., alpha anomeric nucleic acids, etc ). The above term is also intended to include any topological conformation, including single-stranded, double-stranded, partially duplexed, triplex, hairpinned, circular and padlocked conformations. Also included are synthetic molecules that mimic polynucleotides in their ability to bind to a designated sequence via hydrogen bonding and other chemical interactions. Such molecules are known in the art and include, for example, those in which peptide linkages substitute for phosphate linkages in the backbone of the molecule. A reference to a nucleic acid sequence encompasses its complement unless otherwise specified. Thus, a reference to a nucleic acid molecule having a particular sequence should be understood to encompass its complementary strand, with its complementary sequence. The complementary strand is also useful, e.g., for anti-sense therapy, hybridisation probes and PCR primers.

[0027] The term "operably linked" refers to two or more nucleic acid sequence elements that are usually physically linked and are in a functional relationship with each other. For instance, a promoter is operably linked to a coding sequence, if the promoter is able to initiate or regulate the transcription or expression of a coding sequence, in which case the coding sequence should be understood as being "under the control of" the promoter.

[0028] By "pharmaceutically acceptable excipient" is meant any inert substance that is combined with an active molecule such as a drug, agent, or binding molecule for preparing an agreeable or convenient dosage form. The "pharmaceutically acceptable excipient" is an excipient that is non-toxic to recipients at the dosages and concentrations employed, and is compatible with other ingredients of the formulation comprising the drug, agent or binding molecule. Pharmaceutically acceptable excipients are widely applied in the art.

[0029] The term "specifically binding", as used herein, in reference to the interaction of a binding molecule, e.g. an antibody, and its binding partner, e.g. an antigen, means that the interaction is dependent upon the presence of a particular structure, e.g. an antigenic determinant or epitope, on the binding partner. In other words, the antibody preferentially binds or recognizes the binding partner even when the binding partner is present in a mixture of other molecules or organisms. The binding may be mediated by covalent or non-covalent interactions or a combination of both. In yet other words, the term "specifically binding" means immunospecifically binding to an antigen or a fragment thereof and not immunospecifically binding to other antigens. A binding molecule that immunospecifically binds to an antigen may bind to other peptides or polypeptides with lower affinity as determined by, e.g., radioimmunoassays (RIA), enzyme-linked immunosorbent assays (ELISA), BIACORE, or other assays known in the art. Binding molecules or fragments thereof that immunospecifically bind to an antigen may be cross-reactive with related antigens. Preferably, binding molecules or fragments thereof that immunospecifically bind to an antigen do not cross-react with other antigens.

[0030] A "substitution", as used herein, denotes the replacement of one or more amino acids or nucleotides by different amino acids or nucleotides, respectively.

[0031] The term "therapeutically effective amount" refers to an amount of the binding molecule as defined herein that is effective for preventing, ameliorating and/or treating a condition resulting from infection with H5N1.

[0032] The term "treatment" refers to therapeutic treatment as well as prophylactic or preventative measures to cure or halt or at least retard disease progress. Those in need of treatment include those already inflicted with a condition resulting from infection with H5N1 as well as those in which infection with H5N1 is to be prevented. Subjects partially or totally recovered from infection with H5N1 might also be in need of treatment. Prevention encompasses inhibiting or reducing the spread of H5N1 or inhibiting or reducing the onset, development or progression of one or more of the symptoms associated with infection with H5N1.

[0033] The term "vector" denotes a nucleic acid molecule into which a second nucleic acid molecule can be inserted for introduction into a host where it will be replicated, and in some cases expressed. In other words, a vector is capable of transporting a nucleic acid molecule to which it has been linked. Cloning as well as expression vectors are contemplated by the term "vector", as used herein. Vectors include, but are not limited to, plasmids, cosmids, bacterial artificial chromosomes (BAC) and yeast artificial chromosomes (YAC) and vectors derived from bacteriophages or plant or animal (including human) viruses. Vectors comprise an origin of replication recognized by the proposed host and in case of expression vectors, promoter and other regulatory regions recognized by the host. A vector containing a second nucleic acid molecule is introduced into a cell by transformation, transfection, or by making use of viral entry mechanisms. Certain vectors are capable of autonomous replication in a host into which they are introduced (e.g., vectors having a bacterial origin of replication can replicate in bacteria). Other vectors can be integrated into the genome of a host upon introduction into the host, and thereby are replicated along with the host genome.

SUMMARY OF THE INVENTION

[0034] The invention provides human binding molecules capable of specifically binding to influenza virus H5N1 and exhibiting neutralizing activity against H5N1, as defined in the claims. The invention provides binding molecules that bind to an epitope in the haemagglutinin protein that is shared between influenza subtypes and therefore relates to binding molecules that cross-react between H5-, H1-, H2-, H6- and H9 influenza based subtypes, such as H5N1, H1N1 and other influenza strains that contain the HA protein with these particular epitopes. The invention also pertains to nucleic acid molecules encoding at least the binding region of the human binding molecules. The invention further provides for the use of the human binding molecules of the invention in the prophylaxis and/or treatment of a subject having, or at risk of developing, an H5N1 infection. Besides that, the invention pertains to the use of the human binding molecules of the invention in the diagnosis/detection of H5N1.

DETAILED DESCRIPTION

[0035] In a first aspect the present invention encompasses binding molecules capable of specifically binding to influenza virus A, particularly influenza virus A subtype H5N1, as defined in the claims. According to the invention, the binding molecules are human binding molecules. The binding molecules of the invention exhibit neutralizing activity against influenza virus A subtype H5N1. In a further aspect the binding molecules of the invention are capable of specifically binding to and/or have neutralizing activity against different influenza virus H5N1 strains. These strains may be a member of influenza virus H5N1 strains of clade 1, clade 2 or clade 3. Phylogenetic analyses of the HA genes from the 2004 and 2005 H5N1 outbreak showed two different lineages of HA genes, termed dades 1 and 2. Viruses in each of these clades are distributed in non-overlapping geographic regions of Asia. The H5N1 viruses from the Indochina peninsula are tightly clustered within clade 1, whereas H5N1 isolates from several surrounding countries are distinct from clade 1 isolates and belong in the more divergent clade 2. Clade 1 H5N1 viruses were isolated from humans and birds in Vietnam, Thailand, and Cambodia, but only from birds in Laos and Malaysia. The clade 2 viruses were found in viruses isolated exclusively from birds in China, Indonesia, Japan, and South Korea. Viruses isolated from birds and humans in Hong Kong in 2003 and 1997 made up clades T (also categorized in clade 1) and 3, respectively (see WHO Global Influenza Program Surveillance Network, 2005). The hemagglutinins of the clades differ in their amino acid sequences. Examples of clade 1 strains include, but are not limited to, A/Hong Kong/213/03, A/Vietnam/1194/04, A/Vietnam/1203/04 and A/Thailand/1 (ΚΑΝΙ )/2004. Examples of clade 2 strains include, but are not limited to, A/lndonesia/5/05, A/bar headed goose/Qinghai/1A/05, A/turkey/Turkey/1/05 and A/Anhui/1/05. Examples of clade 3 strains include, but are not limited to, A/Hong Kong/156/97 and A/goose/Guangdong/1/96. Other strains can be found, e.g., in WHO Global Influenza Program Surveillance Network, 2005 and on http://www.who.int/csr/disease/avian_influenza/guidelines/recommendationvaccine.pdf Preferably, the binding molecules of the invention are capable of specifically binding to and have neutralizing activity against clade 1, clade 2 and clade 3 strains. The binding molecules of the invention may be capable of specifically binding to influenza virus H5N1 that are viable, living and/or infective or that are in inactivated/attenuated form. Methods for inactivating/attenuating influenza virus H5N1 are well known in the art and include, but are not limited to, treatment with formalin, β-propiolactone (BPL), merthiolate, and/or ultraviolet light.

[0036] The binding molecules of the invention may also be capable of specifically binding to one or more fragments of influenza virus H5N1 such as inter alia a preparation of one or more proteins and/or (poly)peptides derived from subtype H5N1 or one or more recombinantly produced proteins and/or polypeptides of H5N1. For methods of treatment and/or prevention of H5N1 infections the binding molecules are preferably capable of specifically binding to surface accessible proteins of H5N1 such as the surface glycoproteins, hemagglutinin (HA) and neuraminidase (NA), which are required for viral attachment and cellular release, or membrane proteins (M1 and M2). In a specific embodiment the binding molecules of the invention are capable of specifically binding to the HA molecule of H5N1 strains. They may be capable of specifically binding to the HA1 and/or HA2 subunit of the HA molecule. They may be capable of specifically binding to linear or structural and/or conformational epitopes on the HA1 and/or HA2 subunit of the HA molecule. The HA molecule may be purified from viruses or recombinantly produced and optionally isolated before use. Alternatively, HA may be expressed on the surface of cells.

[0037] For diagnostical purposes the binding molecules may also be capable of specifically binding to proteins not present on the surface of H5N1 including the nucleoprotein, the nudeocapsid structural protein, polymerases (PA, PB and PB2), and non-structural proteins (NS1 and NS2). The nucleotide and/or amino acid sequence of proteins of various H5N1 strains can be found in the GenBank-database, NCBI Influenza Virus Sequence Database, Influenza Sequence Database (ISD), EMBL-database and/or other databases. It is well within the reach of the skilled person to find such sequences in the respective databases.

[0038] In another embodiment the binding molecules of the invention are capable of specifically binding to a fragment of the above-mentioned proteins and/or polypeptides, wherein the fragment at least comprises an antigenic determinant recognized by the binding molecules of the invention. An "antigenic determinant" as used herein is a moiety that is capable of binding to a binding molecule of the invention with sufficiently high affinity to form a detectable antigen-binding molecule complex. The binding molecules of the invention may or may not be capable of specifically binding to the extracellular part of HA (also called herein soluble HA (sHA)).

[0039] The binding molecules of the invention can be intact immunoglobulin molecules such as polyclonal or monoclonal antibodies or the binding molecules can be antigen-binding fragments including, but not limited to, Fab, F(ab'), F(ab')2, Fv, dAb, Fd, complementarity determining region (CDR) fragments, single-chain antibodies (scFv), bivalent single-chain antibodies, singlechain phage antibodies, diabodies, triabodies, tetrabodies, and (poly)peptides that contain at least a fragment of an immunoglobulin that is sufficient to confer specific antigen binding to influenza virus H5N1 strains or a fragment thereof. In a preferred embodiment the binding molecules of the invention are human monoclonal antibodies.

[0040] The binding molecules of the invention can be used in non-isolated or isolated form. Furthermore, the binding molecules of the invention can be used alone or in a mixture comprising at least one binding molecule (or variant or fragment thereof) of the invention. In other words, the binding molecules can be used in combination, e.g., as a pharmaceutical composition comprising two or more binding molecules of the invention, variants or fragments thereof. For example, binding molecules having different, but complementary activities can be combined in a single therapy to achieve a desired prophylactic, therapeutic or diagnostic effect, but alternatively, binding molecules having identical activities can also be combined in a single therapy to achieve a desired prophylactic, therapeutic or diagnostic effect. Optionally, the mixture further comprises at least one other therapeutic agent. Preferably, the therapeutic agent such as, e.g., M2 inhibitors (e.g., amantidine, rimantadine) and/or neuraminidase inhibitors (e.g., zanamivir, oseltamivir) is useful in the prophylaxis and/or treatment of an influenza virus H5N1 infection.

[0041] Typically, binding molecules according to the invention can bind to their binding partners, i.e. influenza virus H5N1 or fragments thereof, with an affinity constant (Kd-value) that is lower than 0.2x1 (H M, 1.0x1 O'5 M, 1.0x1 O'6 M, 1.0x1 O'7 M, preferably lower than 1.0x10'8 M, more preferably lower than 1.0x10"9 M, more preferably lower than 1.0x10'10 M, even more preferably lower than 1.0x10"11 M, and in particular lower than 1.0x1 O'12 M. The affinity constants can vary for antibody isotypes. For example, affinity binding for an IgM isotype refers to a binding affinity of at least about 1.0x10"7 M. Affinity constants can for instance be measured using surface plasmon resonance, for example using the BIACORE system (Pharmacia Biosensor AB, Uppsala, Sweden).

[0042] The binding molecules according to the invention may bind to influenza virus H5N1 or a fragment thereof in soluble form such as for instance in a sample or in suspension or may bind to influenza virus H5N1 or a fragment thereof bound or attached to a carrier or substrate, e.g., microtiter plates, membranes and beads, etc. Carriers or substrates may be made of glass, plastic (e.g., polystyrene), polysaccharides, nylon, nitrocellulose, or Teflon, etc. The surface of such supports may be solid or porous and of any convenient shape. Furthermore, the binding molecules may bind to influenza virus H5N1 in purified/isolated or non-purified/non-isolated form.

[0043] The binding molecules of the invention exhibit neutralizing activity. Neutralizing activity can for instance be measured as described herein. Alternative assays measuring neutralizing activity are described in for instance WHO Manual on Animal Influenza Diagnosis and Surveillance, Geneva: World Health Organisation, 2005, version 2002.5. The present invention relates to an isolated human binding molecule that is able to recognize and bind to an epitope in the HA2 subunit of the influenza haemagglutinin protein (HA), characterized in that said binding molecule has neutralizing activity against an influenza virus comprising HA of the H5 subtype, as defined in the claims. Examples of influenza strains that contain such a HA of the H5 subtype and that are important strains in view of pandemic threats are H5N1, H5N2, H5N8, and H5N9. Particularly preferred are binding molecules that at least neutralize the H5N1 influenza strain. Preferably, said binding molecule according to the invention does not depend on an epitope in the HA1 subunit of the HA protein for binding to said HA protein. The known murine antibody that was described in the art (C 179) that also binds to the same epitope in the HA2 domain also depends on binding to an epitope in the HA1 domain of the HA protein. This is disadvantageous as it adds to the possibility of escape mutants that are no longer recognized by the antibody. Moreoever, a number of the antibodies of the present invention (such as CR6307 and CR6323) do not depend on conformational epitopes and recognize the HA2 epitope even in a reduced form (when used in western-blotting). This is an advantage over the antibodies from the art because when a conformational change is induced in the HA protein due to whatever mutation in another part of the protein, such conformational change will not most likely hamper the binding of the antibodies of the present invention to the HA2 epitope, whereas antibodies that do depend on conformation might very well be unable to bind when such mutations occur.

[0044] In another preferred embodiment, the binding molecule according to the invention also has neutralizing activity against an influenza virus comprising HA of the H1 subtype, and preferably wherein said binding molecule also has neutralizing activity against an influenza virus comprising HA of the H2, H6 and/or H9 subtype. It has been shown herein that the binding molecules of the present invention interact with an epitope present in the HA2 epitopes present in the H5, H1, H2, H6, and H9 subtypes, and it has been shown that the binding molecules of the present invention cross-neutralize between influenza subtypes because of this epitope-sharing. It is concluded that the binding molecules of the present invention as defined in the claims that depend on binding to that particular part in the HA2 domain (and not on another -mutational prone- epitope in HA1) can cross-neutralize between influenza virus subtypes as they do not appear to depend on binding to domains within HA1, which may be altered significantly due to antigenic drifts. The skilled person, based on what has been disclosed herein, can now determine whether an antibody indeed cross-reacts with HA proteins from different subtypes and also determine whether they are able to neutralize influenza viruses of different subtypes in vim.

[0045] In another preferred aspect of the invention the binding molecule of the present invention binds to an epitope in the HA2 subunit that is selected from the group consisting of amino acid sequence: GVTNKVNSIIDK (SEQ ID NO:368), GVTNKVNSIINK (SEQ ID NO:369), GVTNKENSIIDK (SEQ ID NO:370), GVTNKVNRIIDK (SEQ ID NO:371), GITNKVNSVIEK (SEQ ID NO:372), GITNKENSVIEK (SEQ ID NO:373), GITNKVNSIIDK (SEQ ID NO:374), and KITSKVNNIVDK (SEQ ID NO:375). As can be concluded from the data shown in Table 13, certain binding molecules of the present invention, CR6261, CR6325, and CR6329 interact with the GVTNKVNSIIDK (SEQ ID NO:368) epitope present in H5N1, and are not hampered by a mutation in the TGLRN epitope in HA1 that do influence the binding of C179. Moreover, some binding molecules, such as CR6307 and CR6323 are not even hampered by a escape mutant, as disclosed in Okuno et al. (1993) with a valine -> glutamic acid mutation at position 6 (exemplified by GVTNKENSIIDK (SEQ ID NO:370)). This epitope is part of an extended alpha helix in the HA2 region. The residues in this putative epitope that are predicted to be most solvent exposed are underlined in bold: GVTNKENSIIDK (SEQ ID NO:370). These amino acids would be most accessible to a binding molecule and thus may form the most important region of the epitope. Consistent with this notion the highlighted ammino acids are absolutly conserved in identity and position in all the sequences presented. This knowledge could be used to predict binding epitopes in influenza subtypes that do not carry the same sequence as above (i.e. H3, H7 and B strains).

[0046] The binding molecule according to the present invention comprises a heavy chain CDR1 region of SEQ ID NO:39, a heavy chain CDR2 region of SEQ ID NO:40, and a heavy chain CDR3 region of SEQ ID NO:41.

[0047] In a preferred embodiment, the binding molecule according to the invention is for a use as a medicament and preferably for the diagnostic, therapeutic and/or prophylactic treatment of influenza infection. In one aspect of such use, said influenza infection is caused by an influenza virus that is associated with a pandemic outbreak, or has the potential to be associated with a pandemic outbreak (see WO 2007/045674 and the tables therein). Preferably, the influenza virus strain that is associated with a pandemic outbreak and wherein the disease caused by these strains can be treated by the binding molecules of the present invention, is selected from the group consisting of H1N1, H5N1, H5N2, H5N8, H5N9, H2-based viruses, and H9N2.

[0048] The present invention also relates to a pharmaceutical composition comprising a binding molecule according to the invention, and a pharmaceutically acceptable excipient.

[0049] In yet another embodiment the invention relates to a use of a binding molecule according to the invention in the preparation of a medicament for the diagnosis, prophylaxis, and/or treatment of an influenza virus infection. Such infections can occur in small populations, but can also spread around the world in seasonal epidemics or, worse, in global pandemics where millions of individuals are at risk. The invention provides binding molecules that can neutralize the infection of influenza strains that cause such seasonal epidemics as well as potential pandemics. Importantly, protection and treatment can be envisioned now with the binding molecules of the present invention in relation to multiple influenza strains as it has been disclosed that due to the binding of an epitope that is shared between HA proteins of different influenza strains, cross-neutralization between such strains is now possible by using the binding molecules of the present invention. This is highly advantageous as the binding molecules can protect mammals when they are administered either before or after infection (as disclosed in the examples), and therefore also when it is unclear (in early stages of occurrence) whether the infection is caused by an H1, an H2, an H5, an H6 or an H9-based strain. Health workers, military forces as well as the general population may be treated prophylactically, or treated upon infection, with the binding molecules of the present invention. Potentially, the binding molecules of the present invention can be prepared and stored in huge stocks because it will provide protection against different pandemic strains, and this will be beneficial in the preparedness of possible influenza pandemics in the future.

[0050] In a preferred embodiment, the human binding molecules according to the invention comprise a heavy chain CDR1 region having the amino acid sequence of SEQ ID NO:39, a heavy chain CDR2 region having the amino acid sequence of SEQ ID NO:40, a heavy chain CDR3 region having the amino acid sequence of SEQ ID NO:41, a light chain CDR1 region having the amino acid sequence of SEQ ID NO:42, a light chain CDR2 region having the amino acid sequence of SEQ ID NO:43, and a light chain CDR3 region having the amino acid sequence of SEQ ID NO:44.

[0051] The CDR regions of the binding molecules of the invention are shown in Table 7. CDR regions are according to Kabat et al. (1991) as described in Sequences of Proteins of Immunological Interest. In an embodiment of th epresent invention binding molecules may comprise two, three, four, five or all six CDR regions as disclosed herein. Preferably, a binding molecule according to the present invention comprises at least two of the CDRs disclosed herein.

[0052] In an embodiment the binding molecules of the invention comprise the VH germline VH1-69 (see Tomlinson IM, Williams SC, Ignatovitch O, Corbett SJ, Winter G. V-BASE Sequence Directory. Cambridge United Kingdom: MRC Centre for Protein Engineering (1997)). In yet another embodiment, the binding molecules according to the invention comprise a heavy chain comprising the variable heavy chain of the amino acid sequence SEQ ID NO:77. In a further embodiment, the binding molecules according to the invention comprise a light chain comprising the variable light chain of the amino acid sequence SEQ ID NO: 103. Table 8 specifies the heavy and light chain variable regions of the binding molecule of the invention.

[0053] Another aspect of the invention includes functional variants of the binding molecules as defined herein. Molecules are considered to be functional variants of a binding molecule according to the invention, if the variants are capable of competing for specifically binding to influenza virus H5N1 or a fragment thereof with the parental binding molecules. In other words, when the functional variants are still capable of binding to influenza virus H5N1 or a fragment thereof. Preferably, the functional variants are capable of competing for specifically binding to at least two (or more) different influenza virus H5N1 strains or fragments thereof that are specifically bound by the parental binding molecules. Furthermore, molecules are considered to be functional variants of a binding molecule according to the invention, if they have neutralizing activity against influenza virus H5N1, preferably against the at least two (or more) influenza virus H5N1 strains against which the parental binding molecule exhibits neutralizing activity. Functional variants include, but are not limited to, derivatives that are substantially similar in primary structural sequence, but which contain e.g. in vitro or in vivo modifications, chemical and/or biochemical, that are not found in the parental binding molecule. Such modifications include inter alia acetylation, acylation, covalent attachment of a nucleotide or nucleotide derivative, covalent attachment of a lipid or lipid derivative, cross-linking, disulfide bond formation, glycosylation, hydroxylation, methylation, oxidation, pegylation, proteolytic processing, phosphorylation, and the like.

[0054] Alternatively, functional variants can be binding molecules as defined in the present invention comprising an amino acid sequence containing substitutions, insertions, deletions or combinations thereof of one or more amino acids compared to the amino acid sequences of the parental binding molecules. Furthermore, functional variants can comprise truncations of the amino acid sequence at either or both the amino or carboxyl termini. Functional variants according to the invention may have the same or different, either higher or lower, binding affinities compared to the parental binding molecule but are still capable of binding to influenza virus H5N1 or a fragment thereof. For instance, functional variants according to the invention may have increased or decreased binding affinities for influenza virus H5N1 or a fragment thereof compared to the parental binding molecules. Preferably, the amino acid sequences of the variable regions, including, but not limited to, framework regions, hypervariable regions, in particular the CDR3 regions, are modified. Generally, the light chain and the heavy chain variable regions comprise three hypervariable regions, comprising three CDRs, and more conserved regions, the so-called framework regions (FRs). The hypervariable regions comprise amino acid residues from CDRs and amino acid residues from hypervariable loops. Functional variants intended to fall within the scope of the present invention have at least about 50% to about 99%, preferably at least about 60% to about 99%, more preferably at least about 70% to about 99%, even more preferably at least about 80% to about 99%, most preferably at least about 90% to about 99%, in particular at least about 95% to about 99%, and in particular at least about 97% to about 99% amino acid sequence homology with the parental binding molecules as defined herein. Computer algorithms such as inter alia Gap or Bestfit known to a person skilled in the art can be used to optimally align amino acid sequences to be compared and to define similar or identical amino acid residues. Functional variants can be obtained by altering the parental binding molecules or parts thereof by general molecular biology methods known in the art including, but not limited to, error-prone PCR, oligonucleotide-directed mutagenesis, site-directed mutagenesis and heavy and/or light chain shuffling. In an embodiment the functional variants of the invention have neutralizing activity against influenza virus H5N1. The neutralizing activity may either be identical, or be higher or lower compared to the parental binding molecules. Henceforth, when the term (human) binding molecule is used, this also encompasses functional variants of the (human) binding molecule.

[0055] In yet a further aspect, the invention includes immunoconjugates, i.e. molecules comprising at least one binding molecule as defined herein and further comprising at least one tag, such as inter alia a detectable moiety/agent. Also contemplated in the present invention are mixtures of immunoconjugates according to the invention or mixtures of at least one immunoconjugates according to the invention and another molecule, such as a therapeutic agent or another binding molecule or immunoconjugate. In a further embodiment, the immunoconjugates of the invention may comprise more than one tag. These tags can be the same or distinct from each other and can be joined/conjugated non-covalently to the binding molecules. The tag(s) can also be joined/conjugated directly to the human binding molecules through covalent bonding. Alternatively, the tag(s) can be joined/conjugated to the binding molecules by means of one or more linking compounds. Techniques for conjugating tags to binding molecules are well known to the skilled artisan.

[0056] The tags of the immunoconjugates of the present invention may be therapeutic agents, but they can also be detectable moieties/agents. Tags suitable in therapy and/or prevention may be toxins or functional parts thereof, antibiotics, enzymes, other binding molecules that enhance phagocytosis or immune stimulation. Immunoconjugates comprising a detectable agent can be used diagnostically to, for example, assess if a subject has been infected with an influenza virus H5N1 strain or monitor the development or progression of an influenza virus H5N1 infection as part of a clinical testing procedure to, e.g., determine the efficacy of a given treatment regimen. However, they may also be used for other detection and/or analytical and/or diagnostic purposes. Detectable moieties/agents include, but are not limited to, enzymes, prosthetic groups, fluorescent materials, luminescent materials, bioluminescent materials, radioactive materials, positron emitting metals, and non-radioactive paramagnetic metal ions. The tags used to label the binding molecules for detection and/or analytical and/or diagnostic purposes depend on the specific detection/analysis/diagnosis techniques and/or methods used such as inter alia immunohistochemical staining of (tissue) samples, flow cytometric detection, scanning laser cytometric detection, fluorescent immunoassays, enzyme-linked immunosorbent assays (ELISAs), radioimmunoassays (RIAs), bioassays (e.g., phagocytosis assays), Western blotting applications, etc. Suitable labels for the detection/analysis/diagnosis techniques and/or methods known in the art are well within the reach of the skilled artisan.

[0057] Furthermore, the human binding molecules or immunoconjugates of the invention can also be attached to solid supports, which are particularly useful for in vitro immunoassays or purification of influenza virus H5N1 or a fragment thereof. Such solid supports might be porous or nonporous, planar or non-planar. The binding molecules of the present invention can be fused to marker sequences, such as a peptide to facilitate purification. Examples include, but are not limited to, the hexa-histidine tag, the hemagglutinin (HA) tag, the myc tag or the flag tag. Alternatively, an antibody can be conjugated to a second antibody to form an antibody heteroconjugate. In another aspect the binding molecules of the invention may be conjugated/attached to one or more antigens. Preferably, these antigens are antigens which are recognized by the immune system of a subject to which the binding molecule-antigen conjugate is administered. The antigens may be identical, but may also differ from each other. Conjugation methods for attaching the antigens and binding molecules are well known in the art and include, but are not limited to, the use of cross-linking agents. The binding molecules of the invention will bind to influenza virus H5N1 and the antigens attached to the binding molecules will initiate a powerful T-cell attack on the conjugate, which will eventually lead to the destruction of the influenza virus H5N1.

[0058] Next to producing immunoconjugates chemically by conjugating, directly or indirectly, via for instance a linker, the immunoconjugates can be produced as fusion proteins comprising the binding molecules of the invention and a suitable tag. Fusion proteins can be produced by methods known in the art such as, e.g., recombinantly by constructing nucleic acid molecules comprising nucleotide sequences encoding the binding molecules in frame with nucleotide sequences encoding the suitable tag(s) and then expressing the nucleic acid molecules.

[0059] It is another aspect of the present invention to provide a nucleic acid molecule encoding at least a binding molecule, functional variant or immunoconjugate according to the invention. Such nucleic acid molecules can be used as intermediates for cloning purposes, e.g. in the process of affinity maturation as described above. In a preferred embodiment, the nucleic acid molecules are isolated or purified.

[0060] The skilled man will appreciate that functional variants of these nucleic acid molecules are also intended to be a part of the present invention. Functional variants are nucleic acid sequences that can be directly translated, using the standard genetic code, to provide an amino acid sequence identical to that translated from the parental nucleic acid molecules.

[0061] Preferably, the nucleic acid molecules encode binding molecules comprising the CDR regions as described above. In a further embodiment the nucleic acid molecules encode binding molecules comprising two, three, four, five or even all six CDR regions of the binding molecules of the invention.

[0062] In another embodiment, the nucleic acid molecules encode binding molecules comprising a heavy chain comprising the variable heavy chain sequences as described above. In another embodiment the nucleic acid molecules encode binding molecules comprising a light chain comprising the variable light chain sequences as described above. The nucleotide sequences of the binding molecules of the invention are given in the Example section (see, e.g., Tables 6 and 8).

[0063] It is another aspect of the invention to provide vectors, i.e. nucleic acid constructs, comprising one or more nucleic acid molecules according to the present invention. Vectors can be derived from plasmids such as inter alia F, R1, RP1, Col, pBR322, TOL, Ti, etc; cosmids; phages such as lambda, lambdoid, M13, Mu, P1, P22, Οβ, T-even, T-odd, T2, T4, T7, etc; plant viruses. Vectors can be used for cloning and/or for expression of the binding molecules of the invention and might even be used for gene therapy purposes. Vectors comprising one or more nucleic acid molecules according to the invention operably linked to one or more expression-regulating nucleic acid molecules are also covered by the present invention. The choice of the vector is dependent on the recombinant procedures followed and the host used. Introduction of vectors in host cells can be effected by inter alia calcium phosphate transfection, virus infection, DEAE-dextran mediated transfection, lipofectamin transfection or electroporation. Vectors may be autonomously replicating or may replicate together with the chromosome into which they have been integrated. Preferably, the vectors contain one or more selection markers. The choice of the markers may depend on the host cells of choice, although this is not critical to the invention as is well known to persons skilled in the art. They include, but are not limited to, kanamycin, neomycin, puromycin, hygromycin, zeocin, thymidine kinase gene from Herpes simplex virus (HSV-TK), dihydrofolate reductase gene from mouse (dhfr). Vectors comprising one or more nucleic acid molecules encoding the human binding molecules as described above operably linked to one or more nucleic acid molecules encoding proteins or peptides that can be used to isolate the human binding molecules are also covered by the invention. These proteins or peptides include, but are not limited to, glutathione-S-transferase, maltose binding protein, metal-binding polyhistidine, green fluorescent protein, luciferase and beta-galactosidase.

[0064] Hosts containing one or more copies of the vectors mentioned above are an additional subject of the present invention. Preferably, the hosts are host cells. Host cells include, but are not limited to, cells of mammalian, plant, insect, fungal or bacterial origin. Bacterial cells include, but are not limited to, cells from Gram-positive bacteria or Gram-negative bacteria such as several species of the genera Escherichia, such as E. coli, and Pseudomonas. In the group of fungal cells preferably yeast cells are used. Expression in yeast can be achieved by using yeast strains such as inter alia Pichia pastoris, Saccharomyces cerevisiae and Hansenula polymorpha. Furthermore, insect cells such as cells from Drosophila and Sf9 can be used as host cells. Besides that, the host cells can be plant cells such as inter alia cells from crop plants such as forestry plants, or cells from plants providing food and raw materials such as cereal plants, or medicinal plants, or cells from ornamentals, or cells from flower bulb crops. Transformed (transgenic) plants or plant cells are produced by known methods, for example, Agrobacterium-mediated gene transfer, transformation of leaf discs, protoplast transformation by polyethylene glycol-induced DNA transfer, electroporation, sonication, microinjection or holistic gene transfer. Additionally, a suitable expression system can be a baculovirus system. Expression systems using mammalian cells such as Chinese Hamster Ovary (CHO) cells, COS cells, BHK cells, NSO cells or Bowes melanoma cells are preferred in the present invention. Mammalian cells provide expressed proteins with posttranslational modifications that are most similar to natural molecules of mammalian origin. Since the present invention deals with molecules that may have to be administered to humans, a completely human expression system would be particularly preferred. Therefore, even more preferably, the host cells are human cells. Examples of human cells are inter alia HeLa, 911, AT1080, A549, 293 and HEK293T cells. In preferred embodiments, the human producer cells comprise at least a functional part of a nucleic acid sequence encoding an adenovirus E1 region in expressible format. In even more preferred embodiments, said host cells are derived from a human retina and immortalized with nucleic acids comprising adenoviral E1 sequences, such as 911 cells or the cell line deposited at the European Collection of Cell Cultures (ECACC), CAMR, Salisbury, Wiltshire SP4 OJG, Great Britain on 29 February 1996 under number 96022940 and marketed under the trademark PER.C6® (PER.C6 is a registered trademark of Crucell Holland B.V.). For the purposes of this application "PER.C6 cells" refers to cells deposited under number 96022940 or ancestors, passages up-stream or downstream as well as descendants from ancestors of deposited cells, as well as derivatives of any of the foregoing. Production of recombinant proteins in host cells can be performed according to methods well known in the art. The use of the cells marketed under the trademark PER.C6® as a production platform for proteins of interest has been described in WO 00/63403 the disclosure of which is incorporated herein by reference in its entirety.

[0065] A method of producing a binding molecule according to the invention is an additional part of the disclosure. The method comprises the steps of a) culturing a host according to the invention under conditions conducive to the expression of the binding molecule, and b) optionally, recovering the expressed binding molecule. The expressed binding molecules can be recovered from the cell free extract, but preferably they are recovered from the culture medium. The above method of producing can also be used to make functional variants of the binding molecules and/or immunoconjugates of the present invention. Methods to recover proteins, such as binding molecules, from cell free extracts or culture medium are well known to the man skilled in the art. Binding molecules, functional variants and/or immunoconjugates as obtainable by the above-described method are also a part of the present invention.

[0066] Alternatively, next to the expression in hosts, such as host cells, the binding molecules and immunoconjugates of the invention can be produced synthetically by conventional peptide synthesizers or in cell-free translation systems using RNA nucleic acid derived from DNA molecules according to the invention. Binding molecules and immunoconjugates as obtainable by the above described synthetic production methods or cell-free translation systems are also a part of the present invention. In yet another embodiment, binding molecules of the present invention can also be produced in transgenic, non-human, mammals such as inter alia rabbits, goats or cows, and secreted into for instance the milk thereof.

[0067] In yet another alternative embodiment, binding molecules according to the present invention, preferably human binding molecules specifically binding to influenza virus H5N1 or a fragment thereof, may be generated by transgenic non-human mammals, such as for instance transgenic mice or rabbits, that express human immunoglobulin genes. Preferably, the transgenic non-human mammals have a genome comprising a human heavy chain transgene and a human light chain transgene encoding all or a portion of the human binding molecules as described above. The transgenic non-human mammals can be immunized with a purified or enriched preparation of influenza virus H5N1 or a fragment thereof. Protocols for immunizing non-human mammals are well established in the art. See Using Antibodies: A Laboratory Manual, Edited by: E. Harlow, D. Lane (1998), Cold Spring Harbor Laboratory, Cold Spring Harbor, New York and Current Protocols in Immunology, Edited by: J.E. Coligan, A.M. Kruisbeek, D.H. Margulies, E.M. Shevach, W. Strober (2001), John Wiley & Sons Inc., New York, the disclosures of which are incorporated herein by reference. Immunization protocols often include multiple immunizations, either with or without adjuvants such as Freund's complete adjuvant and Freund's incomplete adjuvant, but may also include naked DNA immunizations. In another embodiment, the human binding molecules are produced by B-cells, plasma and/or memory cells derived from the transgenic animals. In yet another embodiment, the human binding molecules are produced by hybridomas, which are prepared by fusion of B-cells obtained from the above-described transgenic non-human mammals to immortalized cells. B-cells, plasma cells and hybridomas as obtainable from the above-described transgenic non-human mammals and human binding molecules as obtainable from the above-described transgenic non-human mammals, B-cells, plasma and/or memory cells and hybridomas are also a part of the present invention.

[0068] In yet a further aspect, the invention provides compositions comprising at least a binding molecule preferably a human monoclonal antibody according to the invention, at least a functional variant thereof, at least an immunoconjugate according to the invention or a combination thereof. In addition to that, the compositions may comprise inter alia stabilizing molecules, such as albumin or polyethylene glycol, or salts. Preferably, the salts used are salts that retain the desired biological activity of the binding molecules and do not impart any undesired toxicological effects. If necessary, the human binding molecules of the invention may be coated in or on a material to protect them from the action of acids or other natural or non-natural conditions that may inactivate the binding molecules.

[0069] In yet a further aspect, the invention provides compositions comprising at least a nucleic acid molecule as defined in the present invention. The compositions may comprise aqueous solutions such as aqueous solutions containing salts (e.g., NaCI or salts as described above), detergents (e.g., SDS) and/or other suitable components.

[0070] Furthermore, the present invention pertains to pharmaceutical compositions comprising at least a binding molecule such as a human monoclonal antibody of the invention (or functional fragment or variant thereof), at least an immunoconjugate according to the invention, at least a composition according to the invention, or combinations thereof. The pharmaceutical composition of the invention further comprises at least one pharmaceutically acceptable excipient. Pharmaceutically acceptable excipients are well known to the skilled person. The pharmaceutical composition according to the invention may further comprise at least one other therapeutic agent. Suitable agents are also well known to the skilled artisan.

[0071] In an embodiment the pharmaceutical compositions may comprise two or more binding molecules that have neutralizing activity against influenza virus H5N1. In an embodiment, the binding molecules exhibit synergistic neutralizing activity, when used in combination. In other words, the compositions comprise at least two binding molecules having neutralizing activity, characterized in that the binding molecules act synergistically in neutralizing influenza virus H5N1. As used herein, the term "synergistic" means that the combined effect of the binding molecules when used in combination is greater than their additive effects when used individually. The synergistically acting binding molecules may bind to different structures on the same or distinct fragments of influenza virus H5N1. Away of calculating synergy is by means of the combination index. The concept of the combination index (Cl) has been described by Chou and Talalay (1984). The compositions may also comprise one binding molecule having neutralizing activity and one non-neutralizing H5N1-specific binding molecule. The non-neutralizing and neutralizing H5N1-specific binding molecules may also act synergistically in neutralizing influenza virus H5N1.

[0072] A pharmaceutical composition according to the invention can further comprise at least one other therapeutic, prophylactic and/or diagnostic agent. Preferably, the pharmaceutical composition comprises at least one other prophylactic and/or therapeutic agent. Preferably, said further therapeutic and/or prophylactic agents are agents capable of preventing and/or treating an influenza virus H5N1 infection and/or a condition resulting from such an infection. Therapeutic and/or prophylactic agents include, but are not limited to, anti-viral agents. Such agents can be binding molecules, small molecules, organic or inorganic compounds, enzymes, polynucleotide sequences, anti-viral peptides, etc. Other agents that are currently used to treat patients infected with influenza virus H5N1 are M2 inhibitors (e.g., amantidine, rimantadine) and/or neuraminidase inhibitors (e.g., zanamivir, oseltamivir). These can be used in combination with the binding molecules of the invention. Agents capable of preventing and/or treating an infection with influenza virus H5N1 and/or a condition resulting from such an infection that are in the experimental phase might also be used as other therapeutic and/or prophylactic agents useful in the present invention.

[0073] The binding molecules or pharmaceutical compositions of the invention can be tested in suitable animal model systems prior to use in humans. Such animal model systems include, but are not limited to, mouse, ferret and monkey.

[0074] Typically, pharmaceutical compositions must be sterile and stable under the conditions of manufacture and storage. The binding molecules, immunoconjugates, nucleic acid molecules or compositions of the present invention can be in powder form for reconstitution in the appropriate pharmaceutically acceptable excipient before or at the time of delivery. In the case of sterile powders for the preparation of sterile injectable solutions, the preferred methods of preparation are vacuum drying and freezedrying (lyophilization) that yield a powder of the active ingredient plus any additional desired ingredient from a previously sterile-filtered solution thereof.

[0075] Alternatively, the binding molecules, immunoconjugates, nucleic acid molecules or compositions of the present invention can be in solution and the appropriate pharmaceutically acceptable excipient can be added and/or mixed before or at the time of delivery to provide a unit dosage injectable form. Preferably, the pharmaceutically acceptable excipient used in the present invention is suitable to high drug concentration, can maintain proper fluidity and, if necessary, can delay absorption.

[0076] The choice of the optimal route of administration of the pharmaceutical compositions will be influenced by several factors including the physico-chemical properties of the active molecules wthin the compositions, the urgency of the clinical situation and the relationship of the plasma concentrations of the active molecules to the desired therapeutic effect. For instance, if necessary, the binding molecules of the invention can be prepared with carriers that will protect them against rapid release, such as a controlled release formulation, including implants, transdermal patches, and microencapsulated delivery systems. Biodegradable, biocompatible polymers can inter alia be used, such as ethylene vinyl acetate, polyanhydrides, polyglycolic acid, collagen, polyorthoesters, and polylactic acid. Furthermore, it may be necessary to coat the binding molecules with, or co-administer the binding molecules with, a material or compound that prevents the inactivation of the human binding molecules. For example, the binding molecules may be administered to a subject in an appropriate carrier, for example, liposomes or a diluent.

[0077] The routes of administration can be divided into two main categories, oral and parenteral administration. The preferred administration route is intravenous or by inhalation.

[0078] Oral dosage forms can be formulated inter alia as tablets, troches, lozenges, aqueous or oily suspensions, dispersible powders or granules, emulsions, hard capsules, soft gelatin capsules, syrups or elixirs, pills, dragees, liquids, gels, or slurries. These formulations can contain pharmaceutically excipients including, but not limited to, inert diluents, granulating and disintegrating agents, binding agents, lubricating agents, preservatives, colouring, flavouring or sweetening agents, vegetable or mineral oils, wetting agents, and thickening agents.

[0079] The pharmaceutical compositions of the present invention can also be formulated for parenteral administration. Formulations for parenteral administration can be inter alia in the form of aqueous or non-aqueous isotonic sterile non-toxic injection or infusion solutions or suspensions. The solutions or suspensions may comprise agents that are non-toxic to recipients at the dosages and concentrations employed such as 1,3-butanediol, Ringer's solution, Hank's solution, isotonic sodium chloride solution, oils, fatty acids, local anaesthetic agents, preservatives, buffers, viscosity or solubility increasing agents, water-soluble antioxidants, oil-soluble antioxidants and metal chelating agents.

[0080] In a further aspect, the binding molecules such as human monoclonal antibodies (functional fragments and variants thereof), immunoconjugates, compositions, or pharmaceutical compositions of the invention can be used as a medicament. So, a method of treatment and/or prevention of an influenza virus H5N1 infection using the binding molecules, immunoconjugates, compositions, or pharmaceutical compositions of the invention is another part of the present invention. The above-mentioned molecules can inter alia be used in the diagnosis, prophylaxis, treatment, or combination thereof, of an influenza virus H5N1 infection. They are suitable for treatment of yet untreated patients suffering from an influenza virus H5N1 infection and patients who have been or are treated for an influenza virus H5N1 infection. They may be used for patients such as healthcare workers, relatives of infected subjects, (poultry-)farmers, etc.

[0081] The above-mentioned molecules or compositions may be employed in conjunction with other molecules useful in diagnosis, prophylaxis and/or treatment. They can be used in vitro, ex vivo or in vivo. For instance, the binding molecules such as human monoclonal antibodies (or functional variants thereof), immunoconjugates, compositions or pharmaceutical compositions of the invention can be co-administered with a vaccine against influenza virus H5N1 (if available). Alternatively, the vaccine may also be administered before or after administration of the molecules of the invention. Instead of a vaccine, anti-viral agents can also be employed in conjunction with the binding molecules of the present invention. Suitable anti-viral agents are mentioned above.

[0082] The molecules are typically formulated in the compositions and pharmaceutical compositions of the invention in a therapeutically or diagnostically effective amount. Alternatively, they may be formulated and administered separately. For instance the other molecules such as the anti-viral agents may be applied systemically, while the binding molecules of the invention may be applied intravenously.

[0083] Dosage regimens can be adjusted to provide the optimum desired response (e g., a therapeutic response). A suitable dosage range may for instance be 0.1-100 mg/kg body weight, preferably 0.5-15 mg/kg body weight. Furthermore, for example, a single bolus may be administered, several divided doses may be administered over time or the dose may be proportionally reduced or increased as indicated by the exigencies of the therapeutic situation. The molecules and compositions according to the present invention are preferably sterile. Methods to render these molecules and compositions sterile are well known in the art. The other molecules useful in diagnosis, prophylaxis and/or treatment can be administered in a similar dosage regimen as proposed for the binding molecules of the invention. If the other molecules are administered separately, they may be administered to a patient prior to (e.g., 2 min, 5 min, 10 min, 15 min, 30 min, 45 min, 60 min, 2 hrs, 4 hrs, 6 hrs, 8 hrs, 10 hrs, 12 hrs, 14 hrs, 16 hrs, 18 hrs, 20 hrs, 22 hrs, 24 hrs, 2 days, 3 days, 4 days, 5 days, 7 days, 2 weeks, 4 weeks or 6 weeks before), concomitantly with, or subsequent to (e.g., 2 min, 5 min, 10 min, 15 min, 30 min, 45 min, 60 min, 2 hrs, 4 hrs, 6 hrs, 8 hrs, 10 hrs, 12 hrs, 14 hrs, 16 hrs, 18 hrs, 20 hrs, 22 hrs, 24 hrs, 2 days, 3 days, 4 days, 5 days, 7 days, 2 weeks, 4 weeks or 6 weeks after) the administration of one or more of the human binding molecules or pharmaceutical compositions of the invention. The exact dosing regimen is usually sorted out during clinical trials in human patients.

[0084] Human binding molecules and pharmaceutical compositions comprising the human binding molecules are particularly useful, and often preferred, when to be administered to human beings as in vivo therapeutic agents, since recipient immune response to the administered antibody will often be substantially less than that occasioned by administration of a monoclonal murine, chimeric or humanized binding molecule.

[0085] In another aspect, the invention concerns the use of the binding molecules such as neutralizing human monoclonal antibodies (functional fragments and variants thereof), immunoconjugates, nucleic acid molecules, compositions or pharmaceutical compositions according to the invention in the preparation of a medicament for the diagnosis, prophylaxis, treatment, or combination thereof, of an influenza virus H5N1 infection.

[0086] Next to that, kits comprising at least a binding molecule such as a neutralizing human monoclonal antibody (functional fragments and variants thereof), at least an immunoconjugate, at least a nucleic acid molecule, at least a composition, at least a pharmaceutical composition, at least a vector, at least a host according to the invention or a combination thereof are also a part of the present invention. Optionally, the above-described components of the kits of the invention are packed in suitable containers and labelled for diagnosis, prophylaxis and/or treatment of the indicated conditions. The above-mentioned components may be stored in unit or multi-dose containers as an aqueous, preferably sterile, solution or as a lyophilised, preferably sterile, formulation for reconstitution. The containers may be formed from a variety of materials such as glass or plastic and may have a sterile access port (for example, the container may be an intravenous solution bag or a vial having a stopper pierceable by a hypodermic injection needle). The kit may further comprise more containers comprising a pharmaceutically acceptable buffer. It may further include other materials desirable from a commercial and user standpoint, including other buffers, diluents, filters, needles, syringes, culture medium for one or more of the suitable hosts and, possibly, even at least one other therapeutic, prophylactic or diagnostic agent. Associated with the kits can be instructions customarily included in commercial packages of therapeutic, prophylactic or diagnostic products, that contain information about for example the indications, usage, dosage, manufacture, administration, contra-indications and/or warnings concerning the use of such therapeutic, prophylactic or diagnostic products.

[0087] The disclosure further provides a method of detecting influenza virus H5N1 in a sample, wherein the method comprises the steps of (a) contacting a sample with a diagnostically effective amount of a binding molecule (functional fragments and variants thereof) or an immunoconjugate according to the invention, and (b) determining whether the binding molecule or immunoconjugate specifically binds to a molecule of the sample. The sample may be a biological sample including, but not limited to blood, serum, stool, sputum, nasophargyal aspirates, bronchial lavages, urine, tissue or other biological material from (potentially) infected subjects, or a non-biological sample such as water, drink, etc. The (potentially) infected subjects may be human subjects, but also animals that are suspected as carriers of influenza virus H5N1 might be tested for the presence of the virus using the human binding molecules or immunoconjugates of the invention. The sample may first be manipulated to make it more suitable for the method of detection. Manipulation means inter alia treating the sample suspected to contain and/or containing the virus in such a way that the virus will disintegrate into antigenic components such as proteins, (poly)peptides or other antigenic fragments. Preferably, the human binding molecules or immunoconjugates of the invention are contacted with the sample under conditions which allow the formation of an immunological complex between the human binding molecules and the virus or antigenic components thereof that may be present in the sample. The formation of an immunological complex, if any, indicating the presence of the virus in the sample, is then detected and measured by suitable means. Such methods include, inter alia, homogeneous and heterogeneous binding immunoassays, such as radio-immunoassays (RIA), ELISA, immunofluorescence, immunohistochemistry, FACS, BIACORE and Western blot analyses.

[0088] Preferred assay techniques, especially for large-scale clinical screening of patient sera and blood and blood-derived products are ELISA and Western blot techniques. ELISA tests are particularly preferred. For use as reagents in these assays, the binding molecules or immunoconjugates of the invention are conveniently bonded to the inside surface of microtiter wells. The binding molecules or immunoconjugates of the invention may be directly bonded to the microtiter well. However, maximum binding of the binding molecules or immunoconjugates of the invention to the wells might be accomplished by pre-treating the wells with polylysine prior to the addition of the binding molecules or immunoconjugates of the invention. Furthermore, the binding molecules or immunoconjugates of the invention may be covalently attached by known means to the wells. Generally, the binding molecules or immunoconjugates are used between 0.01 to 100 pg/ml for coating, although higher as well as lower amounts may also be used. Samples are then added to the wells coated with the binding molecules or immunoconjugates of the invention.

[0089] Furthermore, binding molecules of the invention can be used to identify specific binding structures of influenza virus H5N1. The binding structures can be epitopes on proteins and/or polypeptides. They can be linear, but also structural and/or conformational. In one embodiment, the binding structures can be analysed by means of PEPSCAN analysis (see inter alia WO 84/03564, WO 93/09872, Slootstra et al., 1996). Alternatively, a random peptide library comprising peptides from a protein of influenza virus H5N1 can be screened for peptides capable of binding to the binding molecules of the invention. The binding structures/peptides/epitopes found can be used as vaccines and for the diagnosis of influenza virus H5N1 infections. In case fragments other than proteins and/or polypeptides are bound by the binding molecules, binding structures can be identified by mass spectrometry, high performance liquid chromatography and nuclear magnetic resonance.

[0090] In a further aspect, the disclosure provides a method of screening a binding molecule (or a functional fragment or variant thereof) for specific binding to the same epitope of influenza virus H5N1, as the epitope bound by a human binding molecule of the invention, wherein the method comprises the steps of (a) contacting a binding molecule to be screened, a binding molecule of the invention and influenza virus H5N1 or a fragment thereof, (b) measure if the binding molecule to be screened is capable of competing for specifically binding to influenza virus H5N1 or a fragment thereof with the binding molecule of the invention. In a further step it may be determined, if the screened binding molecules that are capable of competing for specifically binding to influenza virus H5N1 or a fragment thereof have neutralizing activity. A binding molecule that is capable of competing for specifically binding to influenza virus H5N1 or a fragment thereof with the binding molecule of the invention is another part of the present invention. In the above-described screening method, "specifically binding to the same epitope" also contemplates specific binding to substantially or essentially the same epitope as the epitope bound by the a binding molecule of the invention. The capacity to block, or compete with, the binding of the binding molecules of the invention to influenza virus H5N1 typically indicates that a binding molecule to be screened binds to an epitope or binding site on influenza virus H5N1 that structurally overlaps with the binding site on influenza virus H5N1 that is immunospecifically recognized by the binding molecules of the invention. Alternatively, this can indicate that a binding molecule to be screened binds to an epitope or binding site which is sufficiently proximal to the binding site immunospecifically recognized by the binding molecules of the invention to sterically or otherwise inhibit binding of the binding molecules of the invention to influenza virus H5N1.

[0091] In general, competitive inhibition is measured by means of an assay, wherein an antigen composition, i.e. a composition comprising influenza virus H5N1 or fragments thereof, is admixed with reference binding molecules, i.e. the binding molecules of the invention, and binding molecules to be screened. Usually, the binding molecules to be screened are present in excess. Protocols based upon ELISAs and Western blotting are suitable for use in such simple competition studies. By using species or isotype secondary antibodies one will be able to detect only the bound reference binding molecules, the binding of which will be reduced by the presence of a binding molecule to be screened that recognizes substantially the same epitope. In conducting a binding molecule competition study between a reference binding molecule and any binding molecule to be screened (irrespective of species or isotype), one may first label the reference binding molecule with a detectable label, such as, e.g., biotin, an enzymatic, a radioactive or other label to enable subsequent identification. Binding molecules identified by these competition assays ("competitive binding molecules" or "cross-reactive binding molecules") include, but are not limited to, antibodies, antibody fragments and other binding agents that bind to an epitope or binding site bound by the reference binding molecule, i.e. a binding molecule of the invention, as well as antibodies, antibody fragments and other binding agents that bind to an epitope or binding site sufficiently proximal to an epitope bound by the reference binding molecule for competitive binding between the binding molecules to be screened and the reference binding molecule to occur. Preferably, competitive binding molecules of the invention will, when present in excess, inhibit specific binding of a reference binding molecule to a selected target species by at least 10%, preferably by at least 25%, more preferably by at least 50%, and most preferably by at least 75%-90% or even greater. The identification of one or more competitive binding molecules that bind to about, substantially, essentially or at the same epitope as the binding molecules of the invention is a straightforward technical matter. As the identification of competitive binding molecules is determined in comparison to a reference binding molecule, i.e. a binding molecule of the invention, it will be understood that actually determining the epitope to which the reference binding molecule and the competitive binding molecule bind is not in any way required in order to identify a competitive binding molecule that binds to the same or substantially the same epitope as the reference binding molecule.

EXAMPLES

[0092] To illustrate the invention, the following examples are provided. The examples are not intended to limit the scope of the invention in anyway.

Example 1

Construction of scFv phage display libraries using RNA extracted from memory B cells [0093] Peripheral blood was collected from normal healthy donors by venapuncture in EDTA anticoagulation sample tubes. A blood sample (45 ml) was diluted twice with PBS and 30 ml aliquots were underlayed with 10 ml Ficoll-Hypaque (Pharmacia) and centrifuged at 900xg for 20 min at room temperature without breaks. The supernatant was removed carefully to just above the white layer containing the lymphocytic and thrombocytic fraction. Next, this layer was carefully removed (-10 ml), transferred to a fresh 50 ml tube and washed three times with 40 ml PBS and spun at 400xg for 10 min at room temperature to remove thrombocytes. The obtained pellet containing lymphocytes was resuspended in RPMI medium containing 2% FBS and the cell number was determined by cell counting. Approximately 1x108 lymphocytes were stained for fluorescent cell sorting using CD24, CD27 and surface IgM as markers for the isolation of IgM memory B cells. A Becton Dickinson Digital Vantage apparatus set in Yield Mode was used for physical memory B cell sorting and isolation. Lymphocytes were gated as the small compact population from the FSC/SSC window. Memory B cells (CD24+/CD27+) were subsequently separated from naive B cells (CD24+/CD27-) and memory T cells (CD24-/CD27+). In a next step, IgM memory B cells (lgM+) were separated from switch memory B cells (IgM-) using IgM expression. In this step IgM memory B cells were sorted in a separate sample tube. 1x108 cells were collected in DMEM/50% FBS and after completion of the sort they were centrifuged at 400xg for 10 min and lysed in 500 pi TRIZOL total RNA extraction solution (Invitrogen). The RNA was extracted from the lysis solution using 200 μΙ chloroform and isopropanol precipitation as detailed in the TRIZOL solution protocol. Next, 1 μΙ Pellet Paint (Novogen) was applied to enhance and visualize the pelleting process. The complete RNA preparation was dissolved in 23 μΙ DEPC treated ultrapure water (Invitrogen) and used for cDNA conversion with Superscript III Reverse Transcriptase (Invitrogen). 1 μΙ Random Hexamers (500 ng/μΙ) (Promega) was added to the RNA sample and mixed and melted at 65°C for 5 min in a heated lid PCR machine. The sample was snap-cooled on wet-ice and the following components were added: 8 μΙ 5X RT buffer (250 mM Tris-HCI pH 8.3, 375 mM KCI, 15 mM MgCl2), 2 μΙ dNTPs (10 mM of each) (Invitrogen), 2 μΙ DTT (100 mM), 2 μΙ RNAse Inhibitor (40 U/μΙ) (Promega), 2 μΙ Superscript III (200 ΙΙ/μΙ) (Invitrogen). The obtained mixture was first incubated for 5 min at room temperature and then transferred to a heated lid PCR machine at 50°C for one hr. The reaction was stopped by heating up to 75°C for 15 min. The cDNA obtained was diluted to 200 μΙ with ultrapure water and stored at -20°C until further use.

[0094] A two round PCR amplification approach was applied using the primer sets shown in Tables 1 and 2 to isolate the immunoglobulin VH and VL regions from the respective donor repertoire. The PCR formulation for amplification used throughout the procedure was as follows: 5 μΙ cDNA template, 32.75 μΙ ultrapure water, 2.5 μΙ of each primer (10 μΜ), 5 μΙ 10X PCR buffer (200 mM Tris-HCI pH 8.4, 500 mM KCI), 1.5 μΙ MgCl2 (50 mM), 0.5 μΙ dNTP's (25 mM of each), 0.25 μΙ Taq polymerase (5 U/μΙ) (Invitrogen). First round amplification on the respective cDNA using the primer sets mentioned in Table 1 yielded 7, 6 and 9 products of about 650 base pairs for respectively VH, Vkappa and Vlambda regions. For IgM memory B cell VH region amplification the OCM constant primer was used in combination with OH1 to OH7. The thermal cycling program for first round amplifications was: 2 min 96°C (denaturation step), 30 cycles of 30 sec 96°C/ 30 sec 55°C/ 60 sec 72°C, 10 min 72°C final elongation and 4°C refrigeration. The products were loaded on and isolated from a 1% agarose gel using gel-extraction columns (Qiagen) and eluted in 50 pi 1 mM Tris-HCI pH 8.0. Ten percent of first round products (5 μΙ) was subjected to second round amplification using the primers mentioned in Table 2. These primers were extended with restriction sites enabling the directional cloning of the respective VL and VH regions into phage display vector PDV-C06. The PCR program for second round amplifications was as follows: 2 min 96°C (denaturation step), 30 cycles of 30 sec 96°C/ 30 sec 60°C/ 60 sec 72°C, 10 min 72°C final elongation and 4°C refrigeration. The second round products (-350 base pairs) were first pooled according to natural occurrence of J segments found in immunoglobulin gene products, resulting in 7, 6 and 9 pools for respectively the VH, Vkappa and Vlambda variable regions (see Tables 3 and 4). To obtain a normalized distribution of immunoglobulin sequences in the immune library the 6 Vkappa and 9 Vlambda light chain pools were mixed according to the percentages mentioned in Table 3. This single final VL pool (3 pg) was digested overnight with Sail and Notl restriction enzymes, loaded on and isolated from a 1.5% agarose gel (-350 base pairs) using Qiagen gel-extraction columns and ligated in Sall-Notl cut PDV-C06 vector (-5000 base pairs) as follows: 10 μΙ PDV-C06 vector (50 ng/μΙ), 7 μΙ VL insert (10 ng/μΙ), 5 μΙ 10X ligation buffer (NEB), 2.5 T4 DNA Ligase (400 U/μΙ) (NEB), 25.5 μΙ ultrapure water (vector to insert ratio was 1:2). Ligation was performed overnight in a water bath of 16°C. Next, the volume was doubled with water, extracted with an equal volume of phenol-chloroform-isoamylalcohol (75:24:1) (Invitrogen) followed by chloroform (Merck) extraction and precipitated with 1 μΙ Pellet Paint (Novogen), 10 μΙ sodium acetate (3 M pH 5.0) and 100 μΙ isopropanol for 2 hrs at -20°C. The obtained sample was subsequently centrifuged at 20.000xg for 30 min at 4°C. The obtained precipitate was washed with 70% ethanol and centrifuged for 10 min at 20.000xg at room temperature. Ethanol was removed by vacuum aspiration and the pellet was air dried for several min and then dissolved in 50 μΙ buffer containing 10 mM Tris-HCI, pH 8.0. 1 μΙ ligation mixture was used for the transformation of 40 μΙ TG-1 electro-competent cells (Stratagene) in a chilled 0.1 cm electroporation cuvette (Biorad) using a Genepulser II apparatus (Biorad) set at 1.7 kV, 200 Ohm, 25 pF (time constant -4,5 msec). Directly after pulse, the bacteria were flushed from the cuvette with 1000 μΙ SOC medium (Invitrogen) containing 5% (w/v) glucose (Sigma) at 37°C and transferred to a 15 ml round bottom culture tube. Another 500 μΙ SOC/glucose was used to flush residual bacteria from the cuvette and was added to the culture tube. Bacteria were recovered by culturing for exactly one hr at 37°C in a shaker incubator at 220 rpm. The transformed bacteria were plated over large 240 mm square petridishes (NUNC) containing 200 ml 2TY agar (16 g/l bacto-tryptone, 10 g/l bacto-yeast extract, 5 g/l NaCI, 15 g/l agar, pH 7.0) supplemented with 50 pg/ml ampicillin and 5% (w/v) glucose (Sigma). A1 to 1000 dilution was plated for counting purposes on 15 cm petridishes containing the same medium. This transformation procedure vwas repeated sequentially twenty times and the complete library was plated over a total of thirty large square petridishes and grown overnight in a 37°C culture stove. Typically, around 1x107 cfu were obtained using the above protocol. The intermediate VL light chain library was harvested from the plates by mildly scraping the bacteria into 10 ml 2TY medium per plate. The cell mass was determined by OD600 measurement and two times 500 OD of bacteria was used for maxi plasmid DNA preparation using two P500 maxiprep columns (Qiagen) according to manufacturer's instructions.

[0095] Analogous to the VL variable regions, the second round VH-JH products were first mixed together to obtain the normal J segment usage distribution (see Table 4), resulting in 7 VH subpools called PH1 to PH7. The pools were mixed to acquire a normalized sequence distribution using the percentages depicted in Table 4, obtaining one VH fraction that was digested with Sfil and Xhol restriction enzymes and ligated in Sfil-Xhol cut PDV-VL intermediate library obtained as described above. The ligation set-up, purification method, subsequent transformation of TG1 and harvest of bacteria was exactly as described for the VL intermediate library (see above). The final library (approximately 5x106 cfu) was checked for insert frequency with a colony PCR using a primer set flanking the inserted VH-VL regions. More than 95% of the colonies showed a correct length insert (see Table 5). The colony PCR products were used for subsequent DNA sequence analysis to check sequence variation and to assess the percentage of colonies showing a complete ORF. This was typically above 70% (see Table 5). The frequency of mutations in the V genes was also analysed. Out of 50 sequences, 47 (94%) were not in germline configuration indicative of a maturation process and consistent with the memory phenotype of the B cells used as an RNA source for the library. Finally, the library was rescued and amplified by using CT helper phages (see WO 02/103012) and was used for phage antibody selection by panning methods as described below.

Example 2

Selection of phages carrying single chain Fv fragments against H5N1 [0096] Antibody fragments were selected using antibody phage display libraries constructed essentially as described above and general phage display technology and MABSTRACT® technology essentially as described in US Patent Number 6,265,150 and in WO 98/15833 (both of which are incorporated by reference herein). Furthermore, the methods and helper phages as described in WO 02/103012 (which is incorporated by reference herein) were used in the present invention.

[0097] Selection was performed against recombinant hemagglutinin (HA) subtype H5 (A/Vietnam/1203/2004; see SEQ ID NO: 110) produced using baculovirus vectors in insect cells (Protein Sciences, CT, USA). The amino acid sequence of HA from isolate A/Vietnam/1194/2004 (HSN1TV) and the consensus amino acid sequence representing HAs from strains isolated in Indonesia and China (HSN1IC) are shown in SEQ ID NO: 111 and SEQ ID NO:112, respectively. Selections were also performed against soluble recombinant HA (sHA) from H5N1. The sequence encoding for the extracellular (soluble) part of HA (sHA) from isolate A/Vietnam/1194/2004 (H5N1), representing the HAs identified in influenza strains isolated in Thailand and Vietnam (sHAof HSN1TV, SEQ ID NO: 113) in 2004 (clade 1) and a consensus sequence representing soluble parts of HAs of H5N1 strains isolated in Indonesia and China (sHAof H5N1IC, SEQ ID NO:114) in 2003/2004 (clade 2) were cloned in an expression vector containing a myc- and his-tag using standard DNA cloning techniques. HAs of H5N1TV and H5N1IC differ at 9 amino acid positions, all located in the HA1 subunit of the molecules. DNA transfections were performed in PER.C6 cells for transient and/or stable expression using standard techniques. sHA was purified from culture supernatant using metal chelate affinity chromatography using HisTrap™ FF Columns (Amersham Biosciences) according to the manufacturer's instructions.

[0098] HA antigens (recombinant HA and sHAof H5N1TV) were diluted in PBS (5.0 pg/ml), added to MaxiSorp™ Nunc-lmmuno Tubes (Nunc) and incubated overnight at 4°C on a rotating wheel. The immunotubes were emptied and washed three times in block buffer (2% non-fat dry milk (ELK) in PBS). Subsequently, the immunotubes were filled completely with block buffer and incubated for 1-2 hrs at room temperature. In addition, immunotubes were coated overnight with anti-myc antibody and incubated with block buffer containing 5 pg/ml myc-tagged sHAof H5N1TV. Aliquots of pooled phage display library (500-1000 pi, 0.5x10 13 - 1x1013 cfu, amplified using CT helper phage (see WO 02/103012)) were blocked in blocking buffer supplemented with 10% nonheat inactivated fetal bovine serum and 2% mouse serum for 1-2 hrs at room temperature. The blocked phage library was added to the immunotubes, incubated for 2 hrs at room temperature, and washed with wash buffer (0.05% (v/v) Tween-20 in PBS) to remove unbound phages. Bound phages were eluted from the respective antigen by incubation with 1 ml of 100 mM triethylamine (TEA) for 10 min at room temperature. Subsequently, the eluted phages were mixed with 0.5 ml of 1 M Tris-HCI pH 7.5 to neutralize the pH. This mixture was used to infect 5 ml of an XL1-Blue E.coli culture that had been grown at 37°C to an OD 600 nm of approximately 0.3. The phages were allowed to infect the XL1-Blue bacteria for 30 min at 37°C. Then, the mixture was centrifuged for 10 min at 3000xg at room temperature and the bacterial pellet was resuspended in 0.5 ml 2-trypton yeast extract (2TY) medium. The obtained bacterial suspension was divided over two 2TY agar plates supplemented with tetracycline, ampicillin and glucose. After incubation overnight of the plates at 37°C, the colonies were scraped from the plates and used to prepare an enriched phage library, essentially as described by De Kruif et al. (1995a) and WO 02/103012. Briefly, scraped bacteria were used to inoculate 2TY medium containing ampicillin, tetracycline and glucose and grown at a temperature of 37°C to an OD 600 nm of -0.3. CT helper phages were added and allowed to infect the bacteria after which the medium was changed to 2TY containing ampicillin, tetracycline and kanamycin. Incubation was continued overnight at 30°C. The next day, the bacteria were removed from the 2TY medium by centrifugation after which the phages in the medium were precipitated using polyethylene glycol (PEG) 6000/NaCI. Finally, the phages were dissolved in 2 ml of PBS with 1% bovine serum albumin (BSA), filter-sterilized and used for the next round of selection.

[0099] Alternatively, phage selections using full-length HA-expressing cell lines were performed. To this end, expression vectors containing the complete coding sequence of full-length HA from isolate A/Vietnam/1194/2004 (H5N1TV) and a consensus sequence representing full-length HAs of H5N1 strains isolated in Indonesia and China (H5N1IC) were used to transfect PER.C6 cells. Flow cytometry analysis using an anti-HA antibody was performed in parallel with each phage selection to assure HA expression by H5N1TV- and H5N1 IC-transfected PER.C6 cells (data not shown). 10x10® untransfected PER.C6 cells were resuspended in 0.5 ml pooled phage library and 0.5 ml PER.C6 culture medium supplemented with 4% ELK and incubated for 1 hr in an end-over-end rotor set at 5 rpm at 4°C. After 5 min centrifugation at 300xg at 4°C of the phage library/untransfected PER.C6 cell mixture, the supernatant containing the phages was subtracted for a second time with 10x10® untransfected PER.C6 cells. The subtracted phage preparation was subsequently mixed with 1x10® HA-expressing PER.C6 cells and incubated for 2 hrs in an end-over-end rotor set at 5 rpm at 4°C. Subsequently, the cells were spun for 2 min at 3000xg and the cell pellet was resuspended in 1 ml PBS/0.05% Tween-20 to wash away unbound phages. The cells were centrifuged for 2 min at 3000xg and the washing was repeated for an additional 5 times. After each wash the cells were transferred to a new tube. Bound phages were eluted from the antigen by incubation with 1 ml of 100 mM TEA for 10 min in an end-over-end rotor set at 5 rpm at room temperature. The cells were spun for 2 min at 3000)¾ and the eluted phages were transferred to a 50 ml tube containing 0.5 ml 1 M Tris-HCI, pH 7.5. Rescue and propagation of the eluted phages was performed as described above. Two rounds of selections were performed before isolation of individual single-chain phage antibodies. After the second round of selection, individual Eco// colonies were used to prepare monoclonal phage antibodies. Essentially, individual colonies were grown to log-phase in 96 well plate format and infected with VCS-M13 helper phages after which phage antibody production was allowed to proceed overnight. The supernatants containing phage antibodies were used directly in ELISA for binding to HA antigens. Alternatively, phage antibodies were PEG/NaCI-precipitated and filter-sterilized for flow cytometry analysis.

Example 3

Validation of the HA specific single-chain phage antibodies [0100] Selected single-chain phage antibodies that were obtained in the screening described above were validated in ELISA for specificity, i.e. binding to HA antigens. For this purpose, baculovirus expressed recombinant HA (Protein Sciences, CT, USA) and purified sHAs of H5N1TV and H5N1IC were coated to Maxisorp™ ELISA plates. Anti-myc mA 9E10 (Roche) was immobilized on Maxisorp™ ELISA plates as negative control antigen. After coating, the plates were washed three times with PBS containing 0.1% v/v Tween-20 and blocked in PBS containing 3% BSAor 2% ELK for 1 hr at room temperature. The selected single-chain phage antibodies were incubated for 1 hr in an equal volume of PBS containing 4% ELK to obtain blocked phage antibodies. The plates were emptied, washed three times with PBS/0.1% Tween-20 and the blocked single-chain phage antibodies were added to the wells. Incubation was allowed to proceed for one hr, the plates were washed with PBS/0.1% Tween-20 and bound phage antibodies were detected (using OD 492nm measurement) using an anti-M13 antibody conjugated to peroxidase. As a control, the procedure was performed simultaneously without single-chain phage antibody and with a negative control single-chain phage antibody. From the selections on the different HA antigens with the IgM memory B cell library, 92 unique single-chain phage antibodies specific for either recombinant HA or sHA were obtained.

[0101] Alternatively, the reactivity of single chain antibodies that were selected for binding to HA-expressing PER.C6 cells was tested using flow cytometry analysis. PEG/NaCI precipitated phages were mixed with an equal volume of PBS/2% ELK blocked for 30 min on ice. The blocked phages were added to pelleted cells (untransfected PER.C6 and HA-expressing PER.C6 cells) and incubated for one hr on ice. The cells were washed three times with PBS/1 % BSA, followed by a 1 minute centrifugation at 300xg, and binding of the single chain phage antibodies to the cells was visualized using a biotinylated anti-M13 antibody (Fitzgerald) followed by streptavidin-phycoerythrin conjugate (Caltag). The selections using HA-expressing PER.C6 cells provided 24 unique single-chain phage antibodies that were not identified during selections using the different recombinant HA proteins.

Example 4

Characterization of the HA specific scFvs [0102] From the selected specific single-chain phage antibodies (scFv) clones plasmid DNAwas obtained and nucleotide and amino acid sequences were determined according to standard techniques. The nucleotide and amino acid sequence and VH and VL gene identity (see Tomlinson IM et al. V-BASE Sequence Directory. Cambridge United Kingdom: MRC Centre for Protein Engineering (1997)) of the scFvs are depicted in Table 6. The CDR regions of the HA- specific immunoglobulins are shown in Table 7.

Example 5

Construction of fully human immunoglobulin molecules (human monoclonal antibodies) from the selected single chain Fvs [0103] Heavy and light chain variable regions of the scFvs were cloned directly by restriction digest for expression in the IgG expression vectors plg-C911-HCgammal (see SEQ ID No: 141), plG-C909-Ckappa (see SEQ ID NO:142), or plg-C910-Clambda (see SEQ ID No: 143). Nucleotide sequences for all constructs were verified according to standard techniques known to the skilled artisan. The resulting expression constructs encoding the human lgG1 heavy and light chains were transiently expressed in combination in 293T cells and supernatants containing human lgG1 antibodies were obtained and produced using standard purification procedures. The human lgG1 antibodies were titrated in a concentration range of between 10 and 0.003 pg/ml against H5 (data not shown). ASARS-CoV specific antibody was included as a control antibody. The lgG1 molecules showed the same pattern of reactivity as demonstrated for the single-chain phage antibodies.

[0104] The nucleotide and amino acid sequences of the heavy and light chain of the antibodies called CR6141, CR6255, CR6257, CR6260, CR6261, CR6262, CR6268, CR6272, CR6296, CR6301, CR6307, CR6310, CR6314, CR6323, CR6325, CR6327, CR6328, CR6329, CR6331, CR6332, CR6334, CR6336, CR6339, CR6342, CR6343 and CR6344 as well as their heavy and light chain variable regions are given in Table 8. Subsequently, binding of the anti-HA IgG to HA-expressing PER.C6 cells was investigated by flow cytometry. Flow cytometry analysis for antibody binding to HA demonstrated that antibodies CR6255, CR6257, CR6260, CR6261, CR6262, CR6268, CR6307, CR6310, CR6314, CR6323, CR6325, CR6331 and CR6344 bound to HA (H5N1TV)-expressing PER.C6 cells (see Table 9). Antibodies CR6261 and CR6344 also displayed binding to untransfected control cells, but the obtained signals were approximately 10-fold lower than the signals obtained for binding to HA (H5N1TV)-expressing PER.C6 cells (see Table 9). No binding of control antibody CR3014 to HA-expressing cells and untransfected control cells was observed.

Example 6

In vitro neutralization of H5N1 influenza virus by H5N1 specific IgGs (virus neutralization assay) [0105] In order to determine whether the selected IgGs were capable of blocking H5N1 infection, in vitro virus neutralization assays (VNA) were performed. The VNA were performed on MDCK cells (ATCC CCL-34). MDCK cells were cultured in MDCK cell culture medium (MEM medium supplemented with antibiotics, 20 mM Hepes and 0.15% (w/v) sodium bicarbonate (complete MEM medium), supplemented with 10% (v/v) fetal bovine serum). The H5N1 reassortant strain NIBRG-14 which was used in the assay was diluted to a titer of 4x103 TCID50/ml (50% tissue culture infective dose per ml), with the titer calculated according to the method of Spearman and Karber. The IgG preparations (200 pg/ml) were serially 2-fold diluted (1:2 - 1:16) in complete MEM medium in duplicate wells. 25 pi of the respective IgG dilution was mixed with 25 pi of virus suspension (100 TCID50/25 pi) and incubated for one hr at 37°C. The suspension was then transferred in duplicate onto 96-well plates containing confluent MDCK cultures in 50 pi complete MEM medium. Prior to use, MDCK cells were seeded at 3x104 cells per well in MDCK cell culture medium, grown until cells had reached confluence, washed with 300-350 pi PBS, pH 7.4 and finally 50 pi complete MEM medium was added to each well. The inoculated cells were cultured for 3-4 days at 33°C and observed daily for the development of cytopathic effect (CPE). CPE was compared to the positive control (NIBRG-14-inoculated cells) and negative controls (mock-inoculated cells). The complete absence of CPE in an individual cell culture was defined as protection. Sheep anti-A/Vietnam/1194/04 H5N1 influenza virus HA (04/214, NIBSC) was used as a positive control in the assay.

[0106] In addition, cultures were tested for the presence of virus using immunohistochemistry. To this end, the culture supernatant was discarded and the cells were fixed with 40% (v/v) acetone and 60% (v/v) methanol for 15 min. Fixed cells were blocked for 30 min at 37°C in blocking buffer (200 mM NaCI, 0.2% (w/v) bovine serum albumin (BSA), 0.01% thimerosal, 0.2% (v/v) Tween-20, 20 mM Tris-HCI, pH 7.45) supplemented with 2% (w/v) BSA and 5% (v/v) goat serum. Subsequently, cells were incubated for one hr at 37°C with 50 pi mouse anti-influenza A monoclonal antibody blend (Chemicon) diluted 1:1000 in washing buffer. After three washes with washing buffer, 50 pi of biotin-conjugated goat anti-mouse IgG (Jackson) diluted 1:1000 in washing buffer was added and incubated for one hr at 37°C. After three washes with washing buffer, 50 pi of streptavidin-peroxidase conjugate (Calbiochem) diluted 1:3000 in washing buffer was added and incubated for 30 min at 37°C. After another three washes with washing buffer, staining was visualized using AEC solution (0.12% (w/v) 3-amino-9-ethylcarbazole, 30% (v/v) N-N-dimethylformamide and 70% (v/v) acetate buffer) containing 1 pi H2O2/I ml AEC solution. After three washes with washing buffer, staining was analysed under a microscope.

[0107] The human anti-HA antibodies called CR6255, CR6257, CR6260, CR6261, CR6262, CR6268, CR6307, CR6310, CR6314, CR6323, CR6325, CR6331 and CR6344 were subjected to the above-described VNA. All antibodies neutralized H5N1 reassortant strain NIBRG-14. The concentrations (in pg/ml) at which these antibodies protect MDCK cultures against CPE are given in Table 10. In wells where CPE was observed, the presence of virus was confirmed by immunohistochemical staining (data not shown).

[0108] In order to determine the neutralizing potency of the H5N1 specific IgGs more accurately, the in vitro virus neutralization assays with NIBRG-14 was repeated, but this time the IgG preparations were further diluted. The IgG preparations (200 pg/ml) were serially 2-fold diluted (1:1 - 1:512) in complete MEM medium and tested in quadruplicate wells in the VNA as described above. The neutralizing potency of the human anti-H5N1 antibodies called CR6255, CR6257, CR6260, CR6261, CR6262, CR6268, CR6272, CR6307, CR6310, CR6314, CR6323, CR6325, CR6327, CR6328, CR6329, CR6331, CR6332, CR6334, CR6336, CR6339, CR6342, CR6343 and CR6344 was determined in the VNA. All antibodies, except CR6272 and CR6339, neutralized H5N1 reassortant strain NIBRG-14. The concentrations (in pg/ml, in the presence of 100 TCID50 of virus) at which these antibodies protect MDCK cultures against CPE are indicated in Table 11. In wells where CPE was observed, the presence of virus was confirmed by immunohistochemical staining (data not shown).

Example 7

Immunoblot analysis of H5N1 specific IgGs [0109] To further investigate the specificity of the anti-HA antibodies, different recombinant hemagglutinin Influenza A antigens were subjected to SDS-PAGE under reducing conditions followed by anti-HA immunoblot analysis. The ΗΑ0 polypeptide is composed of the HA1 and HA2 subunit. Antibody CR5111, a H5N1-specific control antibody, recognized the HA1 subunit and the intact (uncleaved) ΗΑ0 polypeptide of sHAof H5N1TV (see Fig 1, right part, lane 1). In addition, CR5111 recognized the HA1 subunit of recombinant HA, subtype H5 (A/Vietnam/1203/2004 (H5N1); see SEQ ID NO: 110) produced using baculovirus vectors in insect cells (Protein Sciences, CT, USA) (Fig 1, right part, lane 2). Uncleaved ΗΑ0 polypeptide was not detected in this HA preparation. The difference in size between the HA subunits in lanes 1 and 2 might be explained by a different glycosylation of HA expressed in insect cells and PER.C6 cells. CR5111 did not recognize the HA1 and/or ΗΑ0 polypeptides of recombinant HA, subtype H1 (A/New Caledonia/20/99 (H1N1)) (see Fig 1, right part, lane 4) or of recombinant HA, subtype H3 (A/Wyoming/3/2003(H3N2)) (Fig 1, right part, lane 3).

[0110] Antibodies CR6307 and CR6323 recognized the HA2 subunits of sHAof H5N1TV (see Fig 1, left and middle part, lanes 1) and recombinant HA, subtype H5 (A/Vietnam/1203/2004 (H5N1) (see Fig 1, left and middle part, lanes 2). Interestingly, the HA2 subunit as present in the intact, uncleaved ΗΑ0 polypeptides was not recognized. Apparently, the epitope recognized by CR6307 and CR6323 becomes accessible upon cleavage of ΗΑ0. In addition, antibodies CR6307 and CR6323 recognized the HA2 subunit of recombinant HA, subtype H1 (A/New Caledonia/20/99 (H1N1)) (see Fig 1, left and middle part, lanes 4), but not the HA2 subunit of recombinant HA, subtype H3 (A/Wyoming/3/2003(H3N2)) (see Fig 1, left and middle part, lanes 3), both recombinant HAs produced using baculovirus vectors in insect cells (Protein Sciences, CT, USA). Because the binding site of neutralizing antibodies CR6307 and CR6323 is conserved within influenza A strains of the subtype H1 and H5, a molecule comprising the binding site could be considered as (part of a) vaccine capable of inducing a broadly cross-reactive anti-influenza antibody response.

[0111] Next to antibodies CR6307 and CR6323, the antibodies called CR6141, CR6296, and CR6301 were used in immunoblot analysis. Each of the three antibodies was able to bind to the HA2 subunit of sHAof H5N1TV and recombinant HA, subtype H5 (A/Vietnam/1203/2004; H5N1) (data not shown).

Example 8 FACS analysis to determine the subunit specificity of H5H1 specific IgGs [0112] In order to evaluate the contribution of the HA1 subunit to binding of anti-H5N1 antibodies, an assay was set up, wherein the HA1 subunit is released from HA-expressing PER.C6 cells. HA-expressing PER.C6 cells were washed three times wth PBS, pH 7.4, and incubated for 10 min in acidified PBS, pH 4.9. Subsequently, the cells were washed wth PBS, pH 7.4, and treated for 10 min with 10 pg/ml trypsin in PBS, pH 7.4, to cleave ΗΑ0 molecules into disulfide bond-linked HA1 and HA2 subunits. Finally, the cells were incubated for 20 min in 20 mM DTT in PBS, pH 7.4, to release the HA1 subunit from the membrane-anchored HA2 subunit. Untreated and acid/trypsin/DTT-treated cells were washed twice with PBS containing 1% w/v BSA. For flow cytometry analysis, 2.5x1cells were used per staining. No staining of treated and untreated cells with the negative control antibody CR3014 was observed. Antibody CAR5111, which binds to the HA1 subunit in immunoblot analysis, stained the population of untreated HA-expressing PER.C6 cells, while treated cells were not recognized (data not shown). This provides further proof that CR5111 recognizes the HA1 subunit. Treated and untreated cells were stained to a similar extent by the antibodies CR6307 and CR6323 (data not shown). Release of the HA1 subunit obviously did not influence binding of these antibodies further substantiating the results from the immunoblot analysis that the antibodies bind to the HA2 subunit. Antibodies CR6325 and CR6331 bound to untreated cells, while binding to treated cells was markedly reduced compared with binding to untreated cells (data not shown). This suggests that the affinity of the antibodies for their epitope is significantly reduced by the conformational change induced upon acid treatment or by the reduction of the disulfide bond that links the HA1 and HA2 subunit.

Example 9

Hemagglutinin competition ELISA with phage antibodies and IgGs [0113] To identify antibodies that bind to non-overlapping, non-competing epitopes, a hemagglutinin competition ELISA was performed. Nunc-lmmuno™ Maxisorp F96 plates were coated overnight at 4°C with 0.5 pg/ml recombinant HA, subtype H5 (A/Vietnam/1203/2004 (H5N1) (Protein Sciences) in PBS. Uncoated protein was washed away before the wells were blocked with 300 μΙ PBS containing 2% w/v non-fat dry milk (blocking solution) for 1 hr at room temperature. The blocking solution was discarded and 50 μΙ of 10 μg/ml anti-H5N1 IgG in blocking solution was incubated per well for 1 hr at room temperature. Subsequently, 50 μΙ of phage antibody in blocking solution in a concentration twice of the concentration that resulted in 50% maximal binding (as determined in a previous assay) was added per well and incubated for another hr at room temperature. Wells were washed three times with PBS containing 0.1 % v/v Tween-20. Bound phage antibody was detected using a peroxidase-conjugated anti-M 13 antibody. Wells were washed again as described above and the ELISA was further developed by the addition of 100 μΙ of OPD reagent (Sigma). The reaction was stopped by adding 50 μΙ 1 M H2SO4 and then the OD at 492 nm was measured. Binding of phage antibody, in the presence of IgG, was expressed as percentage of binding in the absence of IgG, which was set at 100%. Phage antibody SC05-111 and corresponding IgG CR5111, which recognize an epitope in the HA1 subunit of H5 hemagglutinin were included as controls.

[0114] The results indicate that the majority of the phage antibodies and IgGs bind to an overlapping epitope on recombinant HA, subtype H5 (A/Vietnam/1203/2004 (H5N1)) (data not shown). Binding of SC05-111 phage antibody was blocked by CR5111 IgG, but not by any other IgG, suggesting that the other IgGs recognize an epitope different from the binding region of CR5111. Five IgGs, CR6262, CR6272, CR6307, CR6339 and CR6343 competed to a lower extent for binding than the rest of the IgGs (more than 25% residual binding). For IgGs CR6262, CR6272, CR6339, and CR6343 this can be explained by a lower affinity for HA. This is supported by the observation that the phage antibodies corresponding to these antibodies were competed away more efficiently by the other IgGs. Binding of phage antibody SC06-307 is blocked by IgG CR6307, but less efficiently by the other IgGs. This suggests that SC06-307 and CR6307 recognize a unique epitope which differs from the epitope recognized by the other IgGs.

Example 10

Cross-reactivity ELISA using anti-H5N1 IgGs [0115] To test whether the epitope of the anti-H5N1 antibodies is conserved among HAs other than subtype H5, a hemagglutinin cross-reactivity ELISA was performed. Nunc-lmmuno™ Maxisorp F96 plates (Nunc) were coated overnight at 4°C with 0.5 pg/ml recombinant HA, subtype H1 (A/New Caledonia/20/99 (H1N1)), subtype H3 (A/Wyoming/3/03 (H3N2)), subtype H5 (A/Vietnam/1203/04 (H5N1)), subtype H7 (A/Netherlands/219/03 (H7N7)), and subtype H9 (A/Hong Kong/1073/99 (H9N2)) (Protein Sciences Corp.) in PBS. Additionally, BPL-inactivated virus preparations containing 0.5 pg/ml of HA of A/New Caledonia/20/99 (H1N1), and reassortant strain NIBRG-14 (A/Vietnam/1194/04 (H5N1)) were coated on the plates overnight in PBS. Wells were washed three times with PBS containing 0.1% v/v Tween-20 to remove uncoated protein and subsequently blocked with 300 μΙ PBS containing 2% w/v non-fat dry milk (blocking solution) for 1 hr at room temperature. The blocking solution was discarded and 100 μΙ per well of 5 pg/ml anti-H5N1 antibodies in blocking solution was incubated for 1 hr at room temperature. Wells were washed three times with PBS containing 0.1% v/v Tween-20 and bound antibodies were detected using a peroxidase-conjugated mouse anti-human IgG antibody (Jackson). The reaction was developed and measured as described supra. Table 12 shows that all anti-H5N1 IgGs bound to recombinant HA, subtype H5 (A/Vietnam/1203/2004 (H5N1)) and a BPL-inactivated virus preparation of NIBRG-14, which contains the HA of strain A/Vietnam/1194/2004 (H5N1). Recombinant HAs of subtype H3 and H7 were not recognized by any of the tested anti-H5N1 IgGs. Interestingly, all anti-H5N1 IgGs, with the exception of CR5111 and CR6307, bound to recombinant HA of subtypes H1 and H9, and a BPL-inactivated virus preparation of strain A/New Caledonia/20/99 (H1N1). This indicates that the epitope of the majority of the anti-H5N1 IgGs is conserved among HA molecules of different subtypes.

Example 11

Epitope mapping of anti-H5N1 IgGs [0116] Okuno et al. (1993) and Smirnov et al. (1999) demonstrated the existence of a common epitope shared by the HAs of the influenza A virus subtypes H1, H2, and H5 and neutralization of these subtypes by the murine monoclonal antibody C179 directed against this epitope. This conformational epitope is composed of two different sites which are located in the HA1 and HA2 subunit. Both sites are located in close proximity in the middle of the stem region of the HA molecule. In order to evaluate whether the anti-HA antibodies described supra recognized this epitope, HA molecules containing amino acid substitutions in this region were made.

[0117] The epitope recognized by antibody C 179 (Takara Bio Inc.) has been attributed to regions encompassing residues 318-322 of the HA1 subunit and residues 47-58 of the HA2 subunit (amino acid numbering as described by Okuno et al.1999). Escape viruses containing HAs that carry a Thr to Lys substitution at position 318 in the HA1 subunit or a Val to Glu substitution at position 52 in the HA2 subunit were no longer recognized and neutralized by C179. These mutations (position 318 Thr to Lys, mutant I; position 52 Val to Glu, mutant II), a Leu to Met substitution at position 320 in the HA1 subunit (mutant III, Met320 is present in region 318-322 of HA1 of subtype H3 and H7), a Ser to Arg substitution at position 54 in the HA2 subunit (mutant IV, Arg54 is present in region 47-58 of HA2 of subtype H3 and H7) and an Asp to Asn substitution at position 57 in the HA2 subunit (mutant V, Asn57 is present in region 47-58 of HA2 of strain A/Hong Kong/156/97 (H5N1)) were introduced in full-length HA from isolate A/Vietnam/1194/2004 (H5N1TV) and tranfected in PER.C6 cells. Binding of C 179 and the human anti-HA antibodies to PER.C6 cells expressing these mutants was evaluated by FACS analysis as described supra. Antibody CR5111, which is directed against an epitope in the HA1 subunit, and a polyclonal anti-H5 sheep serum confirmed the expression of H5N1TV and HA mutants by transfected PER.C6 cells (data not shown). No staining vwth the negative control antibody CR3014 or in the absence of antibody was observed (data not shown). As expected, antibody C179 did not recognize mutants I and II, which carried the same amino acid substitutions as the HAs in the C 179 escape viruses (see Okuno etal., 1993). Furthermore, C 179 did not bind to mutant IV, whereas binding of C179 to mutants III and V was unaffected. A similar pattern of reactivity was observed for antibody CR6342, which suggests that antibody C 179 and CR6342 recognize a similar epitope. Antibodies CR6261, CR6325 and CR6329 recognized all mutants, with the exception of mutant II. This suggests that the epitope of antibodies CR6261, CR6325 and CR6329 is different from that of C179. Since substitutions in the HA1 subunit did not abrogate binding of these antibodies, their epitope is most likely located in the HA2 subunit. Antibodies CR6307 and CR6323 recognized all mutants, which suggests that also the epitope of these antibodies is different from that of C 179. A summary of the sequence of the mutants and binding of the antibodies is given in Table 13. In conclusion, the results indicate that antibodies CR6261, CR6325, CR6329, CR6307 and CR6323 are ideal candidates to bind to and neutralize influenza viruses that have mutations in the epitope recognized by the murine monoclonal antibody C 179 and as a consequence thereof are no longer neutralized by this antibody.

Example 12

Prophylactic activity of human IgG monoclonal antibodies against lethal H5N1 challenge in vivo [0118] A lethal dose of influenza H5N1 strain A/HongKong/156/97 was administered to mice in order to study the prophylactic effect of human monoclonal IgG antibodies CR6261, CR6323 and CR6325. One day prior to infection 8 groups of 10 mice each were injected intraperitoneally with different doses of antibody. As a negative control one group of mice was injected with a non-relevant control antibody (CR3014). Clinical signs, weight loss and mortality were monitored until 21 days after infection. This study was conducted to assess the prophylactic effect of the monoclonal human anti-H5N1 IgG antibodies in vivo.

[0119] The H5N1 strain was originally obtained from a 3-year-old child suffering from respiratory disease. The virus was passaged two times on MDCK cells. The batch [Titre 8.1 log TCID50 /ml] used to infect mice was propagated once in embryonated eggs.

[0120] 80 female 7-week-old Balb/c mice were divided in the 8 groups of 10 mice each with the following injections prior to challenge with the H5N1 virus: 1. 1. 15mg/kgCR6261. 2. 2. 5 mg/kg CR6261. 3. 3. 2 mg/kg CR6261. 4. 4. 0.7 mg/kg CR6261. 5. 5. 15 mg/kg CR6323. 6. 6. 15 mg/kg CR6325 7. 7. 500μΙ rabbit anti-H5N3 immune serum (1 OOx diluted). 8. 8. 15 mg/kg CR3014.

[0121] All animals were acclimatized and maintained for a period of 6 days prior to the start of the study. One day prior to infection with H5N1 virus, 500 pi of antibody was administered by intraperitoneal injection. The animals were inoculated intranasally on day 0 with 25 LD50 of virus (approximately 50 μΙ), and followed for 21 days. The actual dose of the virus administered was estimated by titrating a few replicate samples from the inoculum remaining after inoculation of the animals was completed. Virus titers (TCID50/mL) of the inoculum were determined on MDCK cells. The results showed that no inactivation of virus had unintentionally occurred during preparation or administration of the inoculum. Group 8 acted as negative control. The animals in this group were injected with an irrelevant monoclonal antibody (CR3014) on day 0. Group 7 was supposed to act as positive control. The mice in this group were injected with a rabbit polyclonal serum antibody raised against H5N3 influenza virus.

[0122] Clinical signs and weights were assessed daily from day -1 until 21 days after virus inoculation. Clinical signs were scored with a scoring system (0 = no clinical signs; 1 = rough coat; 2 = rough coat, less reactive, passive during handling; 3 = rough coat, rolled up, laboured breathing, passive during handling; 4 = rough coat, rolled up, laboured breathing, does not roll back on stomach when laid down on its back) and recorded. Surviving animals were euthanised and bled on day 21. For analysis of serum IgG antibody levels blood samples were collected from each mouse on day 0. Sera were prepared according to standard procedure. To generate post infection sera, blood was collected from surviving animals on day 21. Sera were stored at -20°C ± 2°C until assayed for the presence of virus specific antibodies. Sera were tested in duplicate using 4 HAU of the H5N1 HK/97 substrate. Titers were expressed as the reciprocal of the highest serum dilution showing HI, starting at a dilution of 1/10.

[0123] All mice were active and appeared healthy without showing signs of disease during the acclimatization period. The average clinical score (total clinical score divided by number of surviving animals in each group) was calculated per day and the results are indicated in Fig 2 (average clinical score per group), Table 14 (clinical scores) and Table 15 (respiratory distress). Onset of negative clinical signs was observed at day 3 after infection in the group that was inoculated with the negative control Ab CR3014 (group 8). Respiratory distress was first recorded on day 6, and lasted for 1 to 4 days. No clinical signs were observed in mice that were treated with 15 mg/kg of CR6325 (group 6). In group 5 (CR6323), one mouse showed mild clinical signs (score 1) from day 5 to 8 and died the next day. In group 1, one mice died on day 13 without having shown any previous clinical signs. Higher Ab doses of CR6261 correlated with later onset and lower clinical scores on average. Respiratory distress was noticed in the lowest dose group (0.7 mg/kg), but not in the higher dose groups (2, 5 and 15 mg/kg). All mice showed improvement in their clinical condition between day 9 and 13 (group 2, 3 and 5) or from day 17 on (group 4). Mice that were injected with the rabbit polyclonal antibody (group 7) developed severe illness within 3 days and then died, demonstrating that the rabbit antibody did not protect against infection in vivo. Two animals (one in group 4 and one in group 8) were euthanized on day 10 and removed from the study, because the animals were considered to be severely ill (score 4).

[0124] The animals infected with H5N1 showed varying degrees of weight loss (Fig 3). Proportional weight loss and the moment of onset were related to antibody dose. In the groups treated with the highest dose of antibodies weight steadily increased over time consistent with age-related weight gain. The group of animals inoculated with the lowest dose of CR6261 lost weight more quickly than the groups of animals receiving higher doses of antibody. The total amount of weight loss was greater in the lower dose groups, with average weight loss of about 15 and 40% of starting weight in the groups inoculated with 2 and 0.7 mg/kg CR6261, respectively. In the lower dose groups average body weight appeared to increase again at the same time as animals showed some clinical improvement.

[0125] Fig 4 shows the number of mice surviving per group on each day. A clear dose-response relationship between the amount of antibody administered-and average survival time was present. Fig 5 shows the mortality in a dose-responsive manner.

The first mice died 7 days after inoculation in the lowest dose group (0.7 mg/kg) and in the group of mice that received the negative control: CR3014. Less than 50% of the animals were protected against death when 0.7 mg/kg of CR6261 antibody was administered. However, 9 to 10 mice survived when the highest dose of antibody was administered. No mice of the negative control group (CR3014) survived, showing that indeed a 100% lethal challenge dose was used in this study.

[0126] To assess whether IgG antibodies are able to render complete protection against infection, an HI assay is performed with sera collected at day 21 from mice that had received 15 mg/kg of CR6261 (group 1). This data should indicate that the mice experienced an H5N1 infection albeit without clinical manifestation.

[0127] These results show that at least three human anti-H5N1 antibodies, identified and developed as disclosed herein (CR6261, CR6323 and CR6325) are each separately able to provide protection against a lethal dose of influenza H5N1 in vivo. A clear dose-response relationship between the amount of CR6261 antibody administered and average survival time was observed. The results show that each monoclonal anti-H5N1 IgG antibody tested was able to prevent clinical manifestation of H5N1 infection in mice when administered one day prior to infection at a dose of 15 mg/kg.

Example 13

Protective and therapeutic effects of human monoclonal anti-H5N1 antibodies administered after an infection with a lethal dose of influenza H5N1 virus in vivo [0128] A study was performed to test the therapeutic effect of the monoclonal antibodies as disclosed herein, exemplified by CR6261, in a post-infection model, against a lethal H5N1 A/HK/97 influenza virus challenge in vivo. The virus batch and the type, and age of mice were the same as used in example 12. As a negative control one group of mice was injected with a non-relevant control antibody (CR2006). Clinical signs, weight loss and mortality were monitored until 21 days after infection.

[0129] 58 female 7-week-old Balb/c mice were divided in 5 groups that received the antibody at different stages after infection, as follows: 1. 1.10 mice; 15 mg/kg CR6261 at 4 hr post infection 2. 2. 14 mice; 15 mg/kg CR6261 at 1 day post infection 3. 3. 10 mice; 15 mg/kg CR6261 at 2 days post infection 4. 4. 10 mice; 15 mg/kg CR6261 at 3 days post infection 5. 5. 14 mice; 15 mg/kg CR2006 at 1 day post infection [0130] All animals were acclimatized and maintained for a period of 6 days prior to the start of the study. The animals were inoculated intranasally on day 0 with 25 LD50 of H5N1 influenza virus (approximately 50 pi), and monitored for 21 days. The actual dose of the virus administered was estimated by titrating a few replicate samples from the inoculum remaining after inoculation of the animals was completed. Virus titers (TCID50/mL) of the inoculum were determined on MDCK cells. The results showed that no inactivation of virus had unintentionally occurred during preparation or administration of the inoculum. At the specified time points after inoculation, 500 μΙ of antibody was administered by intraperitoneal injection. Group 5 acted as negative control. The animals in this group were injected with an irrelevant monoclonal antibody (CR2006) day 1 post-infection.

[0131] Clinical signs and weights were assessed each day from day -1 until day 21. Clinical signs were scored as described in example 12, with a scoring range from 0 to 4. Surviving animals were euthanised and bled on day 21. For assessment of pathological changes, 4 animals of group 2 and 5 were killed on day 6 after challenge. These animals were already pre-selected on day 0, and set apart from the others. For that reason, groups 2 and 5 started with 14 animals, with 10 mice remaining after the selection. Clinical signs and weights were assessed daily from day -1 until 21 days after virus inoculation.

[0132] All mice were active and appeared healthy without showing signs of disease during the acclimatization period. The average clinical score (total clinical score divided by number of surviving animals in each group) was calculated per day and the results are indicated in Fig 6 (average clinical score per group), Table 16 (clinical scores) and Table 17 (respiratory distress). Clearly, all groups contained mice that showed clinical signs already at day 1 after infection. Depending on the time at which the antibody was administered, the clinical signs diminished and in all groups clinical signs were absent again at day 15. In the control group 5, all animals suffered from severe clinical signs and all animals had died, or were euthanized because they reached level 4 in the clinical scores, at day 9. This shows that again a lethal dose of influenza virus was administered to the animals. In Group 1, wherein the animals already received the antibody 4 hr after infection, some animals did not develop clinical signs, whereas others did. The number of animals that did exhibit clinical signs that could be scored are provided in Table 16. Since influenza virus can have a dramatic effect on the respiratory organs, also the respiratory distress was measured and here provided in Table 17. Fig 7 and Table 18 show the number of surviving animals and the mortality rate respectively for all groups. For unknown reasons, one animal in group 1 that received the antibody 4 hr after infection died at day 10. All remaining animals in the groups that received the antibody after the influenza infection survived and were healthy at day 21. This is clearly showa in the body weight data that was obtained from all mice. Fig 8 shows the mean body weight in each group of mice during the 21 days of the study. Although the body weight of all mice decreased upon infection, the body weight did return to normal levels after administration of the antibody. Clearly, the return to normal body weight levels depended on the timing of the antibody treatment, where animals that were treated 4 hr after exposure, recovered rapidly and reached normal levels at day 7, the animals that were treated 3 days after infection, reached their normal body weight at day 17. All animals reached a similar and healthy body weight at the end of the study, at day 21. Clearly, all animals that received the negative control antibody did not regain body weight and measurements stopped at death at day 9.

[0133] These results show that a post-infection treatment with a monoclonal antibody directed against H5N1 influenza virus, as disclosed herein and exemplified by antibody CR6261, can rescue mammalian subjects, as showed herein in mice, after challenge with a lethal dose of H5N1 influenza virus. Even at a late stage, 3 days post-infection, the antibody is able to reverse the clinical symptoms to a level in which no clinical signs could be monitored anymore. Strikingly, at day 21 post-infection, all antibody-treated animals reached normal body weight levels and did not show any remaining clinical signs.

Example 14

In vivo cross-protection against lethal challenge by heterologous influenza subtypes using monoclonal antibodies directed against HA of H5N1.

[0134] As disclosed supra (example 11), some of the antibodies of the present invention apparently recognize a single epitope in the FIA2 domain of the H5 haemagglutinin protein. In example 7 it was shown that certain binding molecules of the present invention could interact with the HA2 epitope in a non-conformational manner, in other words, the form in which the haemagglutinin protein is folded does not seem to hinder the neutralizing activity and the protective effects of these antibodies as disclosed herein.

[0135] The sequences of the influenza haemagglutinin protein parts that are not prone to antigenic drift (= the change of immunodominant regions within the HA1 region of the protein, resulting in the need for yearly updated influenza vaccines) are known in the art. The epitope in HA2 that is recognized by CR6261, CR6325 and CR6329 is contained in the amino acid sequence GVTNKVNSIIDK (SEQ ID NO:368, see Table 13) and is also present in the haemagglutinin proteins of H1 and H9 subtypes, see Table 22. It was shown in example 10 that interaction of the binding molecules of the present invention to the epitope was not limited to HA from H5, but that also HA from H1 and H9 were recognized (see Table 12). Hence, the binding molecules of the present invention recognize an epitope that is present in multiple HA proteins from different influenza serotypes.

[0136] To study the cross-applicability of these antibodies for therapy in vivo, an experiment was performed in mice that was in line with the dosing schedule of the experiment described in example 13. In the present experiment, a very high, lethal dose of another influenza virus related to the 1918 pandemic outbreak and now circulating seasonally in humans, namely H1N1, was administered in mice. Subsequently, the mice were treated with an antibody of the present invention, exemplified by CR6261, and clinical signs, respiratory distress and body weight were monitored for 3 weeks after infection. It turned out that these binding molecules that could rescue mice when infected with H5N1, were also able to rescue mammalian subjects when infected with H1N1, as outlined below.

[0137] A study was performed to test the therapeutic effect of the monoclonal antibodies, exemplified by CR6261, in a postinfection model against a lethal H1N1 A/WSN/33 influenza virus challenge in vivo. The virus batch was obtained from ATCC (VR-219) and was once propagated in embryonated eggs. The titre was 8.5 log TCIDso/ml. As a negative control one group of mice was injected with an irrelevant monoclonal antibody (lgG1, λ named 'CR57', isotype matched negative control antibody). Clinical signs, weight loss and mortality were monitored until 21 days after infection.

[0138] 50 female 6 to 8-week-old Balb/c mice were divided in 5 groups that received the antibody at different stages related to the infection, as follows: 1. 1.10 mice; 15 mg/kg CR6261 at 1 day prior to infection 2. 2. 10 mice; 15 mg/kg CR6261 at 1 day post infection 3. 3. 10 mice; 15 mg/kg CR6261 at 2 days post infection 4. 4. 10 mice; 15 mg/kg CR6261 at 3 days post infection 5. 5. 10 mice; 15 mg/kg neg. contr. CR57 at 1 day post infection [0139] All animals were acclimatized and maintained for a period of at least 4 days prior to the start of the study. The animals were inoculated intranasally on day 0 with a lethal dose of H1N1 virus (6.6 log TCID50; equivalent of 25x the LD50) in approximately 50 μΙ, and monitored. At the specified time points before/after inoculation, 500 pi of antibody was administered by intraperitoneal injection. General health of the mice was monitored throughout the study. Clinical signs and weights were assessed each day from day -1 until day 21. Clinical signs were scored with the scoring rates as disclosed in example 12 and 13, ranging from 0 to 4. Surviving animals were euthanised and bled on day 21.

[0140] The mortality rate for each group is provided in Table 19, showing the number of living mice in each study group throughout the study. Two mice died shortly after the inoculation event (at day 1, one in group 2 and one in group 3) and were excluded from the analysis as pre-defined in the study plan. All mice in the control group 5 were dead at day 9 like in the previous study with H5N1 (see Table 18). The percentage of animals surviving this lethal challenge dose of H1N1 is also plotted in Fig 9. The number of mice showing relevant clinical signs in each group is provided in Table 20. No clinical signs were observed in Group 1, whereas in Group 2, 3 and 4, some mice displayed clinical signs that disappeared completely after day 14 upon inoculation. All animals in Group 5 started showing clinical signs at day 2. No mice in this group recovered. The number of mice showing respiratory distress in category 2 or 3 is given in Table 21. No clinical distress was observed anymore after day 13 in Groups 1-4, whereas all remaining mice in control Group 5 did suffer from severe respiratory distress.

[0141] Fig 10 shows the average body weight of the mice in each study group. Clearly, no measurements are provided for the mice in Group 5 after day 8. As can be seen from this figure, all mice that received the anti-H5N1 antibody and that recovered from the clinical signs did get to their expected body weight level at day 21.

[0142] The antibodies could protect these mice when administered before infection or after infection. Notably, the infection dose was rather high: 25x the LD50 dose, indicating that the antibodies provide a very strong protection against the virus even when present at high titers in the lung. This is clinically relevant as highly pathogenic viruses like H5N1 replicate to high titer after infection and these high viral loads have been linked to the frequently severe outcome in infected humans. Moreover, all protected mice recovered completely from this lethal infection over time. It is concluded that the anti-H5N1 antibodies of the present invention (such as CR6261, CR6325, and CR6329) that bind to (single) epitopes in the HA2 region, a region that is not prone to antigenic drift, provide cross-protection in vivo against multiple influenza serotypes, circumventing the need for antibodies against the highly mutation-sensitive HA1 region. It is to be understood that the binding molecules of the present invention that are not limited by epitopes that are only present in HA from an H5 influenza serotype, can also be used in the prophylactic-, or therapeutic treatment of all influenza serotypes that contain the same epitope in the stable region of HA2, such as H1N1, and influenza viruses comprising H2, H6 and H9 haemagglutinin proteins.

Example 15 Affinity studies [0143] Affinity studies were performed using surface plasmon resonance analysis with a BIAcore3000 analytical system at 25°C and 37°C, using HBS-EP (Biacore AB, Sweden) as running buffer at a flow rate of 75 μΙ/min. IgGs were immobilized on a research grade CM5 4-flow channel (Fc) sensor chip (Biacore AB, Sweden) using amine coupling. A varying amount of HA from an H5N1 virus (A/Vietnam/1203/2004) was injected to analyse the binding interaction between the HA protein and the immobilized IgGs. Regeneration using 20 mM NaOH was performed at the end of each measurement to remove bound HA, while leaving the immobilized IgG on the chip.

[0144] Affinity constants were determined for CR6261, CR6323 and CR6325 antibodies. Five concentrations in 4-fold dilutions of HA were injected (100 μΙ per injection), followed by a dissociation phase of 3600 sec, and regeneration using 10 μΙ 20 mM NaOH. The resulting data were fitted using a 1:1 (Langmuir) model. However, an accurate dissociation constant (KD) could not be calculated. This was due to extremely low dissociation rates at 25°C (even with an extended measurement) leading to unacceptable error in the calculation. When the experiments were repeated at 37°C discernible dissociation did occur but still not sufficiently enough to accurately measure the KD. Experiments are performed to establish a definitive KD for the antibodies. These are estimated to be at least in the single digit nM range and most likely in the pM range of affinity. These experiments show that the binding molecules of the present invention have a very high affinity for their epitope present in the HA protein of influenza virus.

[0145] Below, the details of the nucleic acid and amino acid sequences referred to herein as SEQ ID 140:58-143, SEQ ID 140:212-237, and SEQ ID 140:316-367 are provided. SEQ ID NO:58 gaggtgcagc tggtggagtc tggggctgag gtgaagaagc ctgggtcctc ggtgaaagtc 60 tcttgcaagg cttctggagg ccccttccgc agctatgcta tcagctgggt gcgacaggcc 120 cctggacaag ggcctgagtg gatgggaggg atcatcccta tttttggtac aacaaaatac 180 gcaccgaagt tccagggcag agtcacgatt accgcggacg atttcgcggg cacagtttac 240 atggagctga gcagcctgcg atctgaggac acggccatgt actactgtgc gaaacatatg 300 gggtaccagg tgcgcgaaac tatggacgtc tggggcaaag ggaccacggt caccgtctcg 360 agtgctagca ccaagggccc cagcgtgttc cccctggccc ccagcagcaa gagcaccagc 420 ggcggcacag ccgccctggg ctgcctggtg aaggactact tccccgagcc cgtgaccgtg 480 agctggaaca gcggcgcctt gaccagcggc gtgcacacct tccccgccgt gctgcagagc 540 agcggcctgt acagcctgag cagcgtggtg accgtgccca gcagcagcct gggcacccag 600 acctacatct gcaacgtgaa ccacaagccc agcaacacca aggtggacaa acgcgtggag 660 cccaagagct gcgacaagac ccacacctgc cccccctgcc ctgcccccga gctgctgggc 720 ggaccctccg tgttcctgtt cccccccaag cccaaggaca ccctcatgat cagccggacc 780 cccgaggtga cctgcgtggt ggtggacgtg agccacgagg accccgaggt gaagttcaac 840 tggtacgtgg acggcgtgga ggtgcacaac gccaagacca agccccggga ggagcagtac 900 aacagcacct accgggtggt gagcgtgctc accgtgctgc accaggactg gctgaacggc 960 aaggagtaca agtgcaaggt gagcaacaag gccctgcctg cccccatcga gaagaccatc 1020 agcaaggcca agggccagcc ccgggagccc caggtgtaca ccctgccccc cagccgggag 1080 gagatgacca agaaccaggt gtccctcacc tgtctggtga agggcttcta ccccagcgac 1140 atcgccgtgg agtgggagag caacggccag cccgagaaca actacaagac caccccccct 1200 gtgctggaca gcgacggcag cttcttcctg tacagcaagc tcaccgtgga caagagccgg 1260 tggcagcagg gcaacgtgtt cagctgcagc gtgatgcacg aggccctgca caaccactac 1320 acccagaaga gcctgagcct gagccccggc aag 1353 SEQ ID NO:59 evqlvesgaevkkpgssvkvsckasggpfrsyaiswvr qapgqgpewmggiipifgttkyapkfqgrvtitaddfa gtvymelsslrsedtamyycakhmgyqvretmdvwgkg

TTVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKD

YFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVV

TVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTH

TCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCV

VVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTY

RVVSVLTVLHQDVJLNGKEYKCKVSNKALPAPIEKTISK

AKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSD

IAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDK

SRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

SEQ ID NO:6Q caggtccagc tggtgcagtc tggggctgag gtgaagaagc ctgggtcctc ggtgaaagtc 60 tcttgcaagg cttctggagg ccccttccgc agctatgcta tcagctgggt gcgacaggcc 120 cctggacaag ggcctgagtg gatgggaggg atcatcccta tttttggtac aacaaaatac 180 gcaccgaagt tccagggcag agtcacgatt accgcggacg atttcgcggg cacagtttac 240 atggagctga gcagcctgcg atctgaggac acggccatgt actactgtgc gaaacatatg 300 gggtaccagg tgcgcgaaac tatggacgtc tggggcaaag ggaccacggt caccgtctcg 360 agtgctagca ccaagggccc cagcgtgttc cccctggccc ccagcagcaa gagcaccagc 420 ggcggcacag ccgccctggg ctgcctggtg aaggactact tccccgagcc cgtgaccgtg 480 agctggaaca gcggcgcctt gaccagcggc gtgcacacct tccccgccgt gctgcagagc 540 agcggcctgt acagcctgag cagcgtggtg accgtgccca gcagcagcct gggcacccag 600 acctacatct gcaacgtgaa ccacaagccc agcaacacca aggtggacaa acgcgtggag 660 cccaagagct gcgacaagac ccacacctgc cccccctgcc ctgcccccga gctgctgggc 720 ggaccctccg tgttcctgtt cccccccaag cccaaggaca ccctcatgat cagccggacc 780 cccgaggtga cctgcgtggt ggtggacgtg agccacgagg accccgaggt gaagttcaac 840 tggtacgtgg acggcgtgga ggtgcacaac gccaagacca agccccggga ggagcagtac 900 aacagcacct accgggtggt gagcgtgctc accgtgctgc accaggactg gctgaacggc 960 aaggagtaca agtgcaaggt gagcaacaag gccctgcctg cccccatcga gaagaccatc 1020 agcaaggcca agggccagcc ccgggagccc caggtgtaca ccctgccccc cagccgggag 1080 gagatgacca agaaccaggt gtccctcacc tgtctggtga agggcttcta ccccagcgac 1140 atcgccgtgg agtgggagag caacggccag cccgagaaca actacaagac caccccccct 1200 gtgctggaca gcgacggcag cttcttcctg tacagcaagc tcaccgtgga caagagccgg 1260 tggcagcagg gcaacgtgtt cagctgcagc gtgatgcacg aggccctgca caaccactac 1320 acccagaaga gcctgagcct gagccccggc aag 1353 SEQ ID 140:61

QVQLVQSGAEVKKPGSSVKVSCKASGGPFRSYAISWVR QAPGQGPEWMGG I I P I FGT TKYAPKFQGRVT I TADDFA GTVYMELSSLRSEDTAMYYCAKHMGYQVRETMDVWGKG TTVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKD yfpepvtvswnsgaltsgvhtfpavlqssglyslssvv

TVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTH

TCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCV

VVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTY

RVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISK

AKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSD

IAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDK

SRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK SEQ ID NO:62 gaggtgcagc tggtggagtc tggggctgag gtgaagaagc ctgggtcctc ggtgaaagtc 60 tcttgcaagg cttctggagg ccccttccgc agctatgcta tcagctgggt gcgacaggcc 120 cctggacaag ggcctgagtg gatgggaggg atcatcccta tttttggtac aacaaaatac 180 gcaccgaagt tccagggcag agtcacgatt accgcggacg atttcgcggg cacagtttac 240 atggagctga gcagcctgcg atctgaggac acggccatgt actactgtgc gaaacatatg 300 gggtaccagg tgcgcgaaac tatggacgtc tggggcaaag ggaccacggt caccgtctcg 360 agtgctagca ccaagggccc cagcgtgttc cccctggccc ccagcagcaa gagcaccagc 420 ggcggcacag ccgccctggg ctgcctggtg aaggactact tccccgagcc cgtgaccgtg 480 agctggaaca gcggcgcctt gaccagcggc gtgcacacct tccccgccgt gctgcagagc 540 agcggcctgt acagcctgag cagcgtggtg accgtgccca gcagcagcct gggcacccag 600 acctacatct gcaacgtgaa ccacaagccc agcaacacca aggtggacaa acgcgtggag 660 cccaagagct gcgacaagac ccacacctgc cccccctgcc ctgcccccga gctgctgggc 720 ggaccctccg tgttcctgtt cccccccaag cccaaggaca ccctcatgat cagccggacc 780 cccgaggtga cctgcgtggt ggtggacgtg agccacgagg accccgaggt gaagttcaac 840 tggtacgtgg acggcgtgga ggtgcacaac gccaagacca agccccggga ggagcagtac 900 aacagcacct accgggtggt gagcgtgctc accgtgctgc accaggactg gctgaacggc 960 aaggagtaca agtgcaaggt gagcaacaag gccctgcctg cccccatcga gaagaccatc 1020 agcaaggcca agggccagcc ccgggagccc caggtgtaca ccctgccccc cagccgggag 1080 gagatgacca agaaccaggt gtccctcacc tgtctggtga agggcttcta ccccagcgac 1140 atcgccgtgg agtgggagag caacggccag cccgagaaca actacaagac caccccccct 1200 gtgctggaca gcgacggcag cttcttcctg tacagcaagc tcaccgtgga caagagccgg 1260 tggcagcagg gcaacgtgtt cagctgcagc gtgatgcacg aggccctgca caaccactac 1320 acccagaaga gcctgagcct gagccccggc aag 1353 SEQ ID NO:63

EVQLVESGAEVKKPGSSVKVSCKASGGPFRSYAISWVR

QAPGQGPEWMGGIIPIFGTTKYAPKFQGRVTITADDFA

GTVYMELSSLRSEDTAMYYCAKHMGYQVRETMDVWGKG

TTVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKD

YFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVV

TVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTH

TCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCV

VVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTY

RVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISK

AKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSD

IAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDK

SRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK SEQ ID NO:64 gaggtgcagc tggtggagtc tggggctgag gtgaagaagc ctgggtcctc ggtgaaagtc 60 tcttgcaagg cttctggagg ccccttccgc agctatgcta tcagctgggt gcgacaggcc 120 cctggacaag ggcctgagtg gatgggaggg atcatcccta tttttggtac aacaaaatac 180 gcaccgaagt tccagggcag agtcacgatt accgcggacg atttcgcggg cacagtttac 240 atggagctga gcagcctgcg atctgaggac acggccatgt actactgtgc gaaacatatg 300 gggtaccagg tgcgcgaaac tatggacgtc tggggcaaag ggaccacggt caccgtctcg 360 agtgctagca ccaagggccc cagcgtgttc cccctggccc ccagcagcaa gagcaccagc 420 ggcggcacag ccgccctggg ctgcctggtg aaggactact tccccgagcc cgtgaccgtg 480 agctggaaca gcggcgcctt gaccagcggc gtgcacacct tccccgccgt gctgcagagc 540 agcggcctgt acagcctgag cagcgtggtg accgtgccca gcagcagcct gggcacccag 600 acctacatct gcaacgtgaa ccacaagccc agcaacacca aggtggacaa acgcgtggag 660 cccaagagct gcgacaagac ccacacctgc cccccctgcc ctgcccccga gctgctgggc 720 ggaccctccg tgttcctgtt cccccccaag cccaaggaca ccctcatgat cagccggacc 780 cccgaggtga cctgcgtggt ggtggacgtg agccacgagg accccgaggt gaagttcaac 840 tggtacgtgg acggcgtgga ggtgcacaac gccaagacca agccccggga ggagcagtac 900 aacagcacct accgggtggt gagcgtgctc accgtgctgc accaggactg gctgaacggc 960 aaggagtaca agtgcaaggt gagcaacaag gccctgcctg cccccatcga gaagaccatc 1020 agcaaggcca agggccagcc ccgggagccc caggtgtaca ccctgccccc cagccgggag 1080 gagatgacca agaaccaggt gtccctcacc tgtctggtga agggcttcta ccccagcgac 1140 atcgccgtgg agtgggagag caacggccag cccgagaaca actacaagac caccccccct 1200 gtgctggaca gcgacggcag cttcttcctg tacagcaagc tcaccgtgga caagagccgg 1260 tggcagcagg gcaacgtgtt cagctgcagc gtgatgcacg aggccctgca caaccactac 1320 acccagaaga gcctgagcct gagccccggc aag 1353 SEQ ID NO:65

EVQLVESGAEVKKPGSSVKVSCKASGGPFRSYAISWVR

QAPGQGPEWMGGIIPIFGTTKYAPKFQGRVTITADDFA gtvymelsslrsedtamyycakhmgyqvretmdvwgkg

TTVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKD YFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVV TVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTH TCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCV VVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTY RVVSVLTVLHQDWLNGKEYKCKVSNKALPAPI ΕΚΤ I SK AKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSD IAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDK SRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK SEQ ID NO:66 caggtacagc tgcagcagtc aggggctgag gtgaagaagc ctgggtcctc ggtgaaggtc 60 tcctgcaagg tttccggagt cattttcagc ggcagtgcga tcagctgggt gcgacaggcc 120 cctggacaag gccttgagtg gatgggaggg atcagccctc tctttggcac aacaaattac 180 gcacaaaagt tccagggcag agtcacgatt accgcggacc aatccacgaa cacaacctac 240 atggaggtga acagcctgag atatgaggac acggccgtgt atttctgtgc gcgaggtcca 300 aaatattaca gtgagtacat ggacgtctgg ggcaaaggga ccacggtcac cgtctcgagt 360 gctagcacca agggccccag cgtgttcccc ctggccccca gcagcaagag caccagcggc 420 ggcacagccg ccctgggctg cctggtgaag gactacttcc ccgagcccgt gaccgtgagc 480 tggaacagcg gcgccttgac cagcggcgtg cacaccttcc ccgccgtgct gcagagcagc 540 ggcctgtaca gcctgagcag cgtggtgacc gtgcccagca gcagcctggg cacccagacc 600 tacatctgca acgtgaacca caagcccagc aacaccaagg tggacaaacg cgtggagccc 660 aagagctgcg acaagaccca cacctgcccc ccctgccctg cccccgagct gctgggcgga 720 ccotccgtgt tcctgttccc ccccaagccc aaggacaccc tcatgatcag ccggaccccc 780 gaggtgacct gcgtggtggt ggacgtgagc cacgaggacc ccgaggtgaa gttcaactgg 840 tacgtggacg gcgtggaggt gcacaacgcc aagaccaagc cccgggagga gcagtacaac 900 agcacctacc gggtggtgag cgtgctcacc gtgctgcacc aggactggct gaacggcaag 960 gagtacaagt gcaaggtgag caacaaggcc ctgcctgccc ccatcgagaa gaccatcagc 1020 aaggccaagg gccagccccg ggagccccag gtgtacaccc tgccccccag ccgggaggag 1080 atgaccaaga accaggtgtc cctcacctgt ctggtgaagg gcttctaccc cagcgacatc 1140 gccgtggagt gggagagcaa cggccagccc gagaacaact acaagaccac cccccctgtg 1200 ctggacagcg acggcagctt cttcctgtac agcaagctca ccgtggacaa gagccggtgg 1260 cagcagggca acgtgttcag ctgcagcgtg atgcacgagg ccctgcacaa ccactacacc 1320 cagaagagcc tgagcctgag ccccggcaag 1350 SEQ ID NO:67

QVQLQQSGAEVKKPGSSVKVSCKVSGVIFSGSAISWVR

QAPGQGLEWMGGISPLFGTTNYAQKFQGRVTITADQST nttymevnslryedtavyfcargpkyyseymdvwgkgt

TVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDY fpepvtvswnsgaltsgvhtfpavlqssglyslssvvt

VPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHT cppcpapellggpsvflfppkpkdtlmisrtpevtcvv

VDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYR

VVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKA

KGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDI

AVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKS

RWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK SEQ ID NO:68 caggtccagc tggtacagtc tggggctgag gtgaagaagc ctgggtcctc ggtgaaggtc 60 tcctgcaagg cttctggagg caccttcagt agttatgcta tcagctgggt gcgacaggcc 120 cctggacaag ggcttgagtg gatgggagga atcatgggta tgtttggcac aactaactac 180 gcacagaagt tccagggcag agtcacgatt accgcggacg aattcacgag cgcagcctac 240 atggagctga ggagcctgag atctgaggac acggccgtct actactgtgc gaggtctagt 300 ggttattacc ccgaatactt ccaggactgg ggccagggca ccctggtcac cgtctcgagt 360 gctagcacca agggccccag cgtgttcccc ctggccccca gcagcaagag caccagcggc 420 ggcacagccg ccctgggctg cctggtgaag gactacttcc ccgagcccgt gaccgtgagc 480 tggaacagcg gcgccttgac cagcggcgtg cacaccttcc ccgccgtgct gcagagcagc 540 ggcctgtaca gcctgagcag cgtggtgacc gtgcccagca gcagcctggg cacccagacc 600 tacatctgca acgtgaacca caagcccagc aacaccaagg tggacaaacg cgtggagccc 660 aagagctgcg acaagaccca cacctgcccc ccctgccctg cccccgagct gctgggcgga 720 ccctccgtgt tcctgttccc ccccaagccc aaggacaccc tcatgatcag ccggaccccc 780 gaggtgacct gcgtggtggt ggacgtgagc cacgaggacc ccgaggtgaa gttcaactgg 840 tacgtggacg gcgtggaggt gcacaacgcc aagaccaagc cccgggagga gcagtacaac 900 agcacctacc gggtggtgag cgtgctcacc gtgctgcacc aggactggct gaacggcaag 960 gagtacaagt gcaaggtgag caacaaggcc ctgcctgccc ccatcgagaa gaccatcagc 1020 aaggccaagg gccagccccg ggagccccag gtgtacaccc tgccccccag ccgggaggag 1080 atgaccaaga accaggtgtc cctcacctgt ctggtgaagg gcttctaccc cagcgacatc 1140 gccgtggagt gggagagcaa cggccagccc gagaacaact acaagaccac cccccctgtg 1200 ctggacagcg acggcagctt cttcctgtac agcaagctca ccgtggacaa gagccggtgg 1260 cagcagggca acgtgttcag ctgcagcgtg atgcacgagg ccctgcacaa ccactacacc 1320 cagaagagcc tgagcctgag ccccggcaag 1350 SEQ ID NO:69

QVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYAISWVR

QAPGQGLEWMGGIMGMFGTTNYAQKFQGRVTITADEFT

SAAYMELRSLRSEDTAVYYCARSSGYYPEYFQDWGQGT

LVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDY

FPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVT

VPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHT

CPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVV

VDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYR

VVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKA

KGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDI

AVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKS

RWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

SEQ ID N0:7Q caggtccagc tggtgcagtc tgggggaggc ctggtcaagc ctggggggtc cctgagactc 60 tcctgtgcag cctctggatt caccttcagt agctatagca tgaactgggt ccgccaggct 120 ccagggaagg ggctggagtg ggtctcatcc attagtagta gtagtagtta catatactac 180 gtagactcag tgaagggccg attcaccatc tccagagaca acgccaagaa ctcactgtat 240 ctgcaaatga acagcctgag 'agccgaggac acggctgtgt attactgtgc gagaggtggt 300 gggagctacg gggcctacga aggctttgac tactggggcc agggcaccct ggtcaccgtc 360 tcgagtgcta gcaccaaggg ccccagcgtg ttccccctgg cccccagcag caagagcacc 420 agcggcggca cagccgccct gggctgcctg gtgaaggact acttccccga gcccgtgacc 480 gtgagctgga acagcggcgc cttgaccagc ggcgtgcaca ccttccccgc cgtgctgcag 540 agcagcggcc tgtacagcct gagcagcgtg gtgaccgtgc ccagcagcag cctgggcacc 600 cagacctaca tctgcaacgt gaaccacaag cccagcaaca ccaaggtgga caaacgcgtg 660 gagcccaaga gctgcgacaa gacccacacc tgccccccct gccctgcccc cgagctgctg 720 ggcggaccct ccgtgttcct gttccccccc aagcccaagg acaccctcat gatcagccgg 780 acccccgagg tgacctgcgt ggtggtggac gtgagccacg aggaccccga ggtgaagttc 840 aactggtacg tggacggcgt ggaggtgcac aacgccaaga ceaagccccg ggaggagcag 900 tacaacagca cctaccgggt ggtgagcgtg ctcaccgtgc tgcaccagga ctggctgaac 960 ggcaaggagt acaagtgcaa ggtgagcaac aaggccctgc ctgcccccat cgagaagacc 1020 atcagcaagg ccaagggcca gccccgggag ccccaggtgt acaccctgcc ccccagccgg 1080 gaggagatga ccaagaacca ggtgtccctc acctgtctgg tgaagggctt ctaccccagc 1140 gacatcgccg tggagtggga gagcaacggc cagcccgaga acaactacaa gaccaccccc 1200 cctgtgctgg acagcgacgg cagcttcttc ctgtacagca agctcaccgt ggacaagagc 1260 cggtggcagc agggcaacgt gttcagctgc agcgtgatgc acgaggccct gcacaaccac 1320 tacacccaga agagcctgag cctgagcccc ggcaag 1356 SEQ ID NO:71

QVQLVQSGGGLVKPGGSLRLSCAASGFTFSSYSMNWVR QAPGKGLEWVSSI SSSS SYIYYVDSVKGRFT I SRDNAK NSLYLQMNSLRAEDTAVYYCARGGGSYGAYEGFDYWGQ GTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVK DYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSV VTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKT HTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTC VVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNST YRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTIS KAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPS DIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVD KSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK SEQ ID NO:72 gaggtgcagc tggtggagtc tggggctgag gtgaagaagc ctgggtcctc ggtgaaagtc 60 tcttgcaagg cttctggagg ccccttccgc agctatgcta tcagctgggt gcgacaggcc 120 cctggacaag ggcctgagtg gatgggaggg atcatcccta tttttggtac aacaaaatac 180 gcaccgaagt tccagggcag agtcacgatt accgcggacg atttcgcggg cacagtttac 240 atggagctga gcagcctgcg atctgaggac acggccatgt actactgtgc gaaacatatg 300 gggtaccagg tgcgcgaaac tatggacgtc tggggcaaag ggaccacggt caccgtctcg 360 agtgctagca ccaagggccc cagcgtgttc cccctggccc ccagcagcaa gagcaccagc 420 ggcggcacag ccgccctggg ctgcctggtg aaggactact tccccgagcc cgtgaccgtg 480 agctggaaca gcggcgcctt gaccagcggc gtgcacacct tccccgccgt gctgcagagc 540 agcggcctgt acagcctgag cagcgtggtg accgtgccca gcagcagcct gggcacccag 600 acctacatct gcaacgtgaa ccacaagccc agcaacacca aggtggacaa acgcgtggag 660 cccaagagct gcgacaagac ccacacctgc cccccctgcc ctgcccccga gctgctgggc 720 ggaccctccg tgttcctgtt cccccccaag cccaaggaca ccctcatgat cagccggacc 780 cccgaggtga cctgcgtggt ggtggacgtg agccacgagg accccgaggt gaagttcaac 840 tggtacgtgg acggcgtgga ggtgcacaac gccaagacca agccccggga ggagcagtac 900 aacagcacct accgggtggt gagcgtgctc accgtgctgc accaggactg gctgaacggc 960 aaggagtaca agtgcaaggt gagcaacaag gccctgcctg cccccatcga gaagaccatc 1020 agcaaggcca agggccagcc ccgggagccc caggtgtaca ccctgccccc cagccgggag 1080 gagatgacca agaaccaggt gtccctcacc tgtctggtga agggcttcta ccccagcgac 1140 atcgccgtgg agtgggagag caacggccag cccgagaaca actacaagac caccccccct 1200 gtgctggaca gcgacggcag cttcttcctg tacagcaagc tcaccgtgga caagagccgg 1260 tggcagcagg gcaacgtgtt cagctgcagc gtgatgcacg aggccctgca caaccactac 1320 acccagaaga gcctgagcct gagccccggc aag 1353 SEQ ID NO:73

EVQLVESGAEVKKPGSSVKVSCKASGGPFRSYAISWVR QAPGQGPEWMGGIIPIFGTTKYAPKFQGRVTITADDFA GTVYMELSSLRSEDTAMYYCAKHMGYQVRETMDVWGKG TTVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKD YFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVV TVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTH TCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCV VVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTY RVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKT I SK AKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSD IAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDK SRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK SEQ ID NO:74 gaggtgcagc tggtggagtc tggggctgag gtgaagaagc ctgggtcctc ggtgaaagtc 60 tcttgcaagg cttctggagg ccccttccgc agctatgcta tcagctgggt gcgacaggcc 120 cctggacaag ggcctgagtg gatgggaggg atcatcccta tttttggtac aacaaaatac 180 gcaccgaagt tccagggcag agtcacgatt accgcggacg atttcgcggg cacagtttac 240 atggagctga gcagcctgcg atctgaggac acggccatgt actactgtgc gaaacatatg 300 gggtaccagg tgcgcgaaac tatggacgtc tggggcaaag ggaccacggt caccgtctcg 360 agtgctagca ccaagggccc cagcgtgttc cccctggccc ccagcagcaa gagcaccagc 420 ggcggcacag ccgccctggg ctgcctggtg aaggactact tccccgagcc cgtgaccgtg 480 agctggaaca gcggcgcctt gaccagcggc gtgcacacct tccccgccgt gctgcagagc 540 agcggcctgt acagcctgag cagcgtggtg accgtgccca gcagcagcct gggcacccag 600 acctacatct gcaacgtgaa ccacaagccc agcaacacca aggtggacaa acgcgtggag 660 cccaagagct gcgacaagac ccacacctgc cccccctgcc ctgcccccga gctgctgggc 720 ggaccctccg tgttcctgtt cccccccaag cccaaggaca ccctcatgat cagccggacc 780 cccgaggtga cctgcgtggt ggtggacgtg agccacgagg accccgaggt gaagttcaac 840 tggtacgtgg acggcgtgga ggtgcacaac gccaagacca agccccggga ggagcagtac 900 aacagcacct accgggtggt gagcgtgctc accgtgctgc accaggactg gctgaacggc 960 aaggagtaca agtgcaaggt gagcaacaag gccctgcctg cccccatcga gaagaccatc 1020 agcaaggcca agggccagcc ccgggagccc caggtgtaca ccctgccccc cagccgggag 1080 gagatgacca agaaccaggt gtccctcacc tgtctggtga agggcttcta ccccagcgac 1140 atcgccgtgg agtgggagag caacggccag cccgagaaca actacaagac caccccccct 1200 gtgctggaca gcgacggcag cttcttcctg tacagcaagc tcaccgtgga caagagccgg 1260 tggcagcagg gcaacgtgtt cagctgcagc gtgatgcacg aggccctgca caaccactac 1320 acccagaaga gcctgagcct gagccccggc aag 1353 SEQ ID NO:75 evqlvesgaevkkpgssvkvsckasggpfrsyaiswvr

QAPGQGPEWMGGIIPIFGTTKYAPKFQGRVTITADDFA GTVYMELSSLRSEDTAMYYCAKHMGYQVRETMDVWGKG TTVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKD YFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVV TVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTH TCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCV VVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTY RVVSVLTVLHQDWLNGKEYKCKVSNKALFAPIEKTISK AKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSD IAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDK SRWQQGNVFSC SVMHEALHNHYTQKSLSLS PGK SEQ ID NO:76 gaggtgcagc tggtggagtc tggggctgag gtgaagaagc cagggtcctc ggtgaaggtc 60 tcctgtaagg cctctggagg caccttctcc agctatggta tcagctgggt gcgacaggcc 120 cctggacaag ggcttgagtg gatgggagac atcatcggta tgtttggttc aacaaactac 180 gcacagaact tccagggcag actcacgatt accgcggacg aatccacgag cacagcctac 240 atggagctga gcagcctgag atctgaggac acggccgtgt attactgtgc gagaagtagt 300 ggttattacc ctgcatacct cccccactgg ggccagggca ccttggtcac cgtctcgagt 360 gctagcacca agggccccag cgtgttcccc ctggccccca gcagcaagag caccagcggc 420 ggcacagccg ccctgggctg cctggtgaag gactacttcc ccgagcccgt gaccgtgagc 480 tggaacagcg gcgccttgac cagcggcgtg cacaccttcc ccgccgtgct gcagagcagc 540 ggcctgtaca gcctgagcag cgtggtgacc gtgcccagca gcagcctggg cacccagacc 600 tacatctgca acgtgaacca caagcccagc aacaccaagg tggacaaacg cgtggagccc 660 aagagctgcg acaagaccca cacctgcccc ccctgccctg cccccgagct gctgggcgga 720 ccctccgtgt tcctgttccc ccccaagccc aaggacaccc tcatgatcag ccggaccccc 780 gaggtgacct gcgtggtggt ggacgtgagc cacgaggacc ccgaggtgaa gttcaactgg 840 tacgtggacg gcgtggaggt gcacaacgcc aagaccaagc cccgggagga gcagtacaac 900 agcacctacc gggtggtgag cgtgctcacc gtgctgcacc aggactggct gaacggcaag 960 gagtacaagt gcaaggtgag caacaaggcc ctgcctgccc ccatcgagaa gaccatcagc 1020 aaggccaagg gccagccccg ggagccccag gtgtacaccc tgccccccag ccgggaggag 1080 atgaccaaga accaggtgtc cctcacctgt ctggtgaagg gcttctaccc cagcgacatc 1140 gccgtggagt gggagagcaa cggccagccc gagaacaact acaagaccac cccccctgtg 1200 ctggacagcg acggcagctt cttcctgtac agcaagctca ccgtggacaa gagccggtgg 1260 cagcagggca acgtgttcag ctgcagcgtg atgcacgagg ccctgcacaa ccactacacc 1320 cagaagagcc tgagcctgag ccccggcaag 1350 SEQ ID NO:77

EVQLVESGAEVKKPGSSVKVSCKASGGTFSSYGISWVR

QAPGQGLEWMGDIIGMFGSTNYAQNFQGRLTITADEST

STAYMELSSLRSEDTAVYYCARSSGYYPAYLPHWGQGT

LVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDY

FPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVT

VPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHT

CPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVV

VDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYR

VVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKA

KGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDI

AVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKS

RWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK SEQ ID NO:78 gaggtgcagc tggtggagtc tggggctgag gtgaagaagc cggggtcctc ggtgaaggtc 60 tcctgcaagg cttctggagg caccttcagc ttctattcta tgagctgggt gcgacaggcc 120 cctggacaag gacttgagtg gatgggaggg atcatcccta tgtttggtac aacaaactac 180 gcacagaagt tccagggcag agtcacgatt accgcggtcg aatccacgag cacagcctac 240 atggaggtga gcagcctgag atctgaggac acggccgttt attactgtgc gagaggtgat 300 aagggtatct actactacta catggacgtc tggggcaaag ggaccacggt caccgtctcg 360 agtgctagca ccaagggccc cagcgtgttc cccctggccc ccagcagcaa gagcaccagc 420 ggcggcacag ccgccctggg ctgcctggtg aaggactact tccccgagcc cgtgaccgtg 480 agctggaaca gcggcgcctt gaccagcggc gtgcacacct tccccgccgt gctgcagagc 540 agcggcctgt acagcctgag cagcgtggtg accgtgccca gcagcagcct gggcacccag 600 acctacatct gcaacgtgaa ccacaagccc agcaacacca aggtggacaa acgcgtggag 660 cccaagagct gcgacaagac ccacacctgc cccccctgcc ctgcccccga gctgctgggc 720 ggaccctccg tgttcctgtt cccccccaag cccaaggaca ccctcatgat cagccggacc 780 cccgaggtga cctgcgtggt ggtggacgtg agccacgagg accccgaggt gaagttcaac 840 tggtacgtgg acggcgtgga ggtgcacaac gccaagacca agccccggga ggagcagtac 900 aacagcacct accgggtggt gagcgtgctc accgtgctgc accaggactg gctgaacggc 960 aaggagtaca agtgcaaggt gagcaacaag gccctgcctg cccccatcga gaagaccatc 1020 agcaaggcca agggccagcc ccgggagccc caggtgtaca ccctgccccc cagccgggag 1080 gagatgacca agaaccaggt gtccctcacc tgtctggtga agggcttcta ccccagcgac 1140 atcgccgtgg agtgggagag caacggccag cccgagaaca actacaagac caccccccct 1200 gtgctggaca gcgacggcag cttcttcctg tacagcaagc tcaccgtgga caagagccgg 1260 tggcagcagg gcaacgtgtt cagctgcagc gtgatgcacg aggccctgca caaccactac 1320 acccagaaga gcctgagcct gagccccggc aag 1353 SEQ ID NO:79

EVQLVESGAEVKKPGSSVKVSCKASGGTFSFYSMSWVR

QAPGQGLEWMGGIIPMFGTTNYAQKFQGRVTITAVEST

STAYMEVSSLRSEDTAVYYCARGDKGIYYYYMDVWGKG

TTVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKD

YFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVV

TVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTH

TCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCV

VVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTY

RVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISK

AKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSD

IAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDK

SRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

SEQ ID NO:8Q gaggtgcagc tggtggagtc tggggctgag gtgaagaagc ctgggtcctc ggtgaaggtc 60 tcctgcaagg cttctggagg caccttcagc agctatgcta tcagctgggt gcgacaggcc 120 cctggacaag ggcttgagtg gatgggaggg atcatcggta tgttcggtac agcaaactac 180 gcacagaagt tccagggcag agtcacgatt accgcggacg aatttacgag cacagcctac 240 atggagctga gcagcctgag atctgaggac acggccgtgt attactgtgc gagaggaaat 300 tattactatg agagtagtct cgactactgg ggccagggaa ccctggtcac cgtctcgagt 360 gctagcacca agggccccag cgtgttcccc ctggccccca gcagcaagag caccagcggc 420 ggcacagccg ccctgggctg cctggtgaag gactacttcc ccgagcccgt gaccgtgagc 480 tggaacagcg gcgccttgac cagcggcgtg cacaccttcc ccgccgtgct gcagagcagc 540 ggcctgtaca gcctgagcag cgtggtgacc gtgcccagca gcagcctggg cacccagacc 600 tacatctgca acgtgaacca caagcccagc aacaccaagg tggacaaacg cgtggagccc 660 aagagctgcg acaagaccca cacctgcccc ccctgccctg cccccgagct gctgggcgga 720 ccctccgtgt tcctgttccc ccccaagccc aaggacaccc tcatgatcag ccggaccccc 780 gaggtgacct gcgtggtggt ggacgtgagc cacgaggacc ccgaggtgaa gttcaactgg 840 tacgtggacg gcgtggaggt gcacaacgcc aagaccaagc cccgggagga gcagtacaac 900 agcacctacc gggtggtgag cgtgctcacc gtgctgcacc aggactggct gaacggcaag 960 gagtacaagt gcaaggtgag caacaaggcc ctgcctgccc ccatcgagaa gaccatcagc 1020 aaggccaagg gccagccccg ggagccccag gtgtacaccc tgccccccag ccgggaggag 1080 atgaccaaga accaggtgtc cctcacctgt ctggtgaagg gcttctaccc cagcgacatc 1140 gccgtggagt gggagagcaa cggccagccc gagaacaact acaagaccac cccccctgtg 1200 ctggacagcg acggcagctt cttcctgtac agcaagctca ccgtggacaa gagccggtgg 1260 cagcagggca acgtgttcag ctgcagcgtg atgcacgagg ccctgcacaa ccactacacc 1320 cagaagagcc tgagcctgag ccccggcaag 1350 SEQ ID NO:81

EVQLVESGAEVKKPGSSVKVSCKASGGTFSSYAISWVR

QAPGQGLEWMGGIIGMFGTANYAQKFQGRVTITADEFT

STAYMELSSLRSEDTAVYYCARGNYYYESSLDYWGQGT

LVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDY

FPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVT

VPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHT

CPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVV

VDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYR

VVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKA

KGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDI

AVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKS rwqqgnvfscsvmhealhnhytqkslslspgk SEQ ID NO:82 caggtgcagc tggtgcagtc tggggctgag gtgaagaagc ctgggtcctc ggtgagagtc 60 tcctgcaagg cttctggaag catcttcaga aactatgcta tgagctgggt gcgacaggcc 120 cctggacaag ggcttgagtg gatgggaggg atcatcgcta tttttgggac accaaagtac 180 gcacagaagt tccagggcag agtcacgatt accgcggacg aatcgacgag cactgtctac 240 atggaactga gcggactgag atctgaggac acggccatgt attactgtgc gaggattccc 300 cactataatt ttggttcggg gagttatttc gactactggg gccagggaac cctggtcacc 360 gtctcgagtg ctagcaccaa gggccccagc gtgttccccc tggcccccag cagcaagagc 420 accagcggcg gcacagccgc cctgggctgc ctggtgaagg actacttccc cgagcccgtg 480 accgtgagct ggaacagcgg cgccttgacc agcggcgtgc acaccttccc cgccgtgctg 540 cagagcagcg gcctgtacag cctgagcagc gtggtgaccg tgcccagcag cagcctgggc 600 acccagacct acatctgcaa cgtgaaccac aagcccagca acaccaaggt ggacaaacgc 660 gtggagccca agagctgcga caagacccac acctgccccc cctgccctgc ccccgagctg 720 ctgggcggac cctccgtgtt cctgttcccc cccaagccca aggacaccct catgatcagc 780 cggacccccg aggtgacctg cgtggtggtg gacgtgagcc acgaggaccc cgaggtgaag 840 ttcaactggt acgtggacgg cgtggaggtg cacaacgcca agaccaagcc ccgggaggag 900 cagtacaaca gcacctaccg ggtggtgagc gtgctcaccg tgctgcacca ggactggctg 960 aacggcaagg agtacaagtg caaggtgagc aacaaggccc tgcctgcccc catcgagaag 1020 accatcagca aggccaaggg ccagccccgg gagccccagg tgtacaccct gccccccagc 1080 cgggaggaga tgaccaagaa ccaggtgtcc ctcacctgtc tggtgaaggg cttctacccc 1140 agcgacatcg ccgtggagtg ggagagcaac ggccagcccg agaacaacta caagaccacc 1200 ccccctgtgc tggacagcga cggcagcttc ttcctgtaca gcaagctcac cgtggacaag 1260 agccggtggc agcagggcaa cgtgttcagc tgcagcgtga tgcacgaggc cctgcacaac 1320 cactacaccc agaagagcct gagcctgagc cccggcaag 1359 SEQ ID NO:83

QVQLVQSGAEVKKPGSSVRVSCKASGSIFRNYAMSWVR QAPGQGLEWMGG I I A I FGT PKYAQKFQGRVT I TADEST STVYMELSGLRSEDTAMYYCARIPHYNFGSGSYFDYWG QGTLVTVSSASTKGPSVFPLAPSSKSTSGG'TAALGCLV KDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSS VVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDK THTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVT CVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNS TYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTI SKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYP SDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTV DKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK SEQ ID NO:84 tcctatgtgc tgactcagcc accctcagcg tctgggaccc ccgggcagag ggtcaccatc 60 tcttgttctg gaagcacgtt caacatcgga agtaatgctg tagactggta ccggcagctc 120 ccaggaacgg cccccaaact cctcatctat agtaataatc agcggccctc aggggtccct 180 gaccgattct ctggctccag gtctggcacc tcagcctccc tggccatcag tgggctccag 240 tctgaggatg aggctgatta ttactgtgca gcatgggatg acatcctgaa tgttccggta 300 ttcggcggag ggaccaagct gaccgtccta ggtgcggccg caggccagcc caaggccgct 360 cccagcgtga ccctgttccc cccctcctcc gaggagctgc aggccaacaa ggccaccctg 420 gtgtgcctca tcagcgactt ctaccctggc gccgtgaccg tggcctggaa ggccgacagc 480 agccccgtga aggccggcgt ggagaccacc acccccagca agcagagcaa caacaagtac 540 gccgccagca gctacctgag cctcaccccc gagcagtgga agagccaccg gagctacagc 600 tgccaggtga cccacgaggg cagcaccgtg gagaagaccg tggcccccac cgagtgcagc 660 SEQ ID NO:85

SYVLTQPPSASGTPGQRVTISCSGSTFNIGSNAVDWYR

QLPGTAPKLLIYSNNQRPSGVPDRFSGSRSGTSASLAI

SGLQSEDEADYYCAAWDDILNVPVFGGGTKLTVLGAAA

GQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAV

TVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTP eqwkshrsyscqvthegstvektvaptecs SEQ ID NO:86 cagtctgccc tgactcagcc tgccgccgtg tctgggtctc ctggacagtc gatcaccatc 60 tcctgcactg gaaccagcag tgacgttggt ggttataact atgtctcctg gtaccaacag 120 cacccaggca aagcccccaa actcatgatt tatgaggtca gtaatcggcc ctcaggggtt 180 tctaatcgct tctctggctc caagtctggc aacacggcct ccctgaccat ctctgggctc 240 caggctgagg acgaggctga ttattactgc agctcatata caagcagcag cacttatgtc 300 ttcggaactg ggaccaaggt caccgtccta ggtgcggccg caggccagcc caaggccgct 360 cccagcgtga ccctgttccc cccctcctcc gaggagctgc aggccaacaa ggccaccctg 420 gtgtgcctca tcagcgactt ctaccctggc gccgtgaccg tggcctggaa ggccgacagc 480 agccccgtga aggccggcgt ggagaccacc acccccagca agcagagcaa caacaagtac 540 gccgccagca gctacctgag cctcaccccc gagcagtgga agagccaccg gagctacagc 600 tgccaggtga cccacgaggg cagcaccgtg gagaagaccg tggcccccac cgagtgcagc 660 SEQ ID NO:87

QSALTQPAAVSGSPGQSITISCTGTSSDVGGYNYVSWY

QQHPGKAPKLMIYEVSNRPSGVSNRFSGSKSGNTASLT

ISGLQAEDEADYYCSSYTSSSTYVFGTGTKVTVLGAAA

GQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAV

TVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTP

EQWKSHRSYSCQVTHEGSTVEKTVAPTECS SEQ ID NO:88 tcctatgtgc tgactcagcc accctcagtc tctgggaccc ccgggcagag ggtcaccatc 60 tcttgctctg gaagccgctc caacgtcgga gataattctg tatattggta tcaacacgtc 120 ccagaaatgg cccccaaact cctcgtctat aagaatactc aacggccctc aggagtccct 180 gcccggtttt ccggctccaa gtctggcact tcagcctccc tggccatcat tggcctccag 240 tccggcgatg aggctgatta ttattgtgtg gcatgggatg acagcgtaga tggctatgtc 300 ttcggatctg ggaccaaggt caccgtccta ggtgcggccg caggccagcc caaggccgct 360 cccagcgtga ccctgttccc cccctcctcc gaggagctgc aggccaacaa ggccaccctg 420 gtgtgcctca tcagcgactt ctaccctggc gccgtgaccg tggcctggaa ggccgacagc 480 agccccgtga aggccggcgt ggagaccacc acccccagca agcagagcaa caacaagtac 540 gccgccagca gctacctgag cctcaccccc gagcagtgga agagccaccg gagctacagc 600 tgccaggtga cccacgaggg cagcaccgtg gagaagaccg tggcccccac cgagtgcagc 660 SEQ ID NO:89

SYVLTQPP S V S G T PGQRVT I SCSGSRSNVGDNSVYWYQ HVPEMAPKLLVYKNTQRPSGVPARFSGSKSGTSASLAI IGLQSGDEADYYCVAWDDSVDGYVFGSGTKVTVLGAAA GQPKAAPSVT LFP PS SEELQANKATLVCL I SDFY PGAV TVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTP EQWKSHRSYSCQVTHEGSTVEKTVAPTECS SEQ ID NQ:90 cagtctgtgt tgacgcagcc gccctcagtg tctgcggccc caggacagaa ggtcaccatc 60 tcctgctctg gaagcagctc caacattggg aatgattatg tatcctggta ccagcagctc 120 ccaggaacag cccccaaact cctcatttat gacaataata agcgaccctc agggattcct 180 gaccgattct ctggctccaa gtctggcacg tcagccaccc tgggcatcac cggactccag 240 actggggacg aggccaacta ttactgcgca acatgggatc gccgcccgac tgcttatgtt 300 gtcttcggcg gagggaccaa gctgaccgtc ctaggtgcgg ccgcaggcca gcccaaggcc 360 gctcccagcg tgaccctgtt ccccccctcc tccgaggagc tgcaggccaa caaggccacc 420 ctggtgtgcc tcatcagcga cttctaccct ggcgccgtga ccgtggcctg gaaggccgac 480 agcagccccg tgaaggccgg cgtggagacc accaccccca gcaagcagag caacaacaag 540 tacgccgcca gcagctacct gagcctcacc cccgagcagt ggaagagcca ccggagctac 600 agctgccagg tgacccacga gggcagcacc gtggagaaga ccgtggcccc caccgagtgc 660 age 663 SEQ ID NO:91

QSVLTQPPSVSAAPGQKVTISCSGSSSNIGNDYVSWYQ

QLPGTAPKLLIYDNNKRPSGIPDRFSGSKSGTSATLGI

TGLQTGDEANYYCATWDRRPTAYVVFGGGTKLTVLGAA

AGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGA

VTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLT

PEQWKSHRSYSCQVTHEGSTVEKTVAPTECS SEQ ID NO:92 gacatccaga tgacccagtc tccatcctcc ctgtctgcat ctgtaggaga cagagtcacc 60 atcacttgcc gggegagtea gggeattage agttatttag cctggtatca gcagaagcca 120 gggaaagttc ctacactcct gatetatgat gcatccactt tgcgatcagg ggtcccatct 180 egetteagtg geagtggate tgegaeagat ttcactctca ccatcagcag cctgcagcct 240 gaagatgttg caacttatta ctgtcaaagg tataaeagtg cccccccgat caccttcggc 300 caagggacac gaetggagat taaacgtgcg gccgcaccca gcgtgttcat cttccccccc 360 tccgacgagc agetgaagag cggcaccgcc agcgtggtgt gcctgctgaa caacttctac 420 ccccgggagg ccaaggtgca gtggaaggtg gacaacgccc tgeagagegg caacagccag 480 gagagegtga ccgagcagga cagcaaggac tccacctaca gcctgagcag caccctcacc 540 ctgagcaagg ccgactacga gaagcacaag gtgtacgcct gegaggtgae ccaccagggc 600 ctgagcagcc ccgtgaccaa gagetteaae cggggcgagt gt 642 SEQ ID NO:93

DIQMTQSPSSLSASVGDRVTITCRASQGISSYLAWYQQ

KPGKVPTLLIYDASTLRSGVPSRFSGSGSATDFTLTIS

SLQPEDVATYYCQRYNSAPPITFGQGTRLEIKRAAAPS

VFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDN

ALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHK

VYACEVTHQGLSSPVTKSFNRGEC SEQ ID NO:94 cagtctgtgc tgactcagcc accctcagag tccgtgtccc eaggaeagae agccagcgtc 60 acctgctctg gacataaatt gggggataaa tatgtttegt ggtatcagca gaagccaggc 120 cagtcccctg tattactcat ctatcaagat aaeaggegge cctcagggat ccctgagcga 180 tteatagget ccaactctgg gaacacagcc actctgacca teagegggae ccaggctctg 240 gatgaggetg actattactg teaggegtgg gaeageagea ctgcggtttt eggeggaggg 300 accaagctga ccgtcctagg tgcggccgca ggccagccca aggccgctcc cagcgtgacc 360 ctgttccccc cctcctccga ggagctgcag gccaacaagg ccaccctggt gtgcctcatc 420 agegaettet accctggcgc cgtgaccgtg gcctggaagg ccgacagcag ccccgtgaag 480 gccggcgtgg agaccaccac ccccagcaag cagagcaaca aeaagtaege cgccagcagc 540 tacctgagcc tcacccccga gcagtggaag agccaccgga gctacagctg ccaggtgacc 600 cacgagggca gcaccgtgga gaagaccgtg gcccccaccg agtgeage 648 SEQ ID NO:95

QSVLTQPPSESVSPGQTASVTCSGHKLGDKYVSWYQQK pgqspvlliyqdnrrpsgiperfigsnsgntatltisg tqaldeadyycqawdsstavfgggtkltvlgaaagqpk

AAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAW

KADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWK

SHRSYSCQVTHEGSTVEKTVAPTECS SEQ ID NO:96 gaaattgtgc tgactcagtc tccaggcacc ctgtctttgt ctccagggga aagagccacc 60 ctctcctgca gggccagtca gcgtgttagc agctacttag cctggtacca acagaaacct 120 ggccaggctc ccaggctcct catctatggt gcatccacca gggccgctgg catcccagac 180 aggttcagtg gcagtgggtc tgggacagac ttcactctca ccatcagcag actggagcct 240 gaagattctg cagtgtatta ctgtcagcag tatggtagga caccgctcac tttcggcgga 300 gggaccaagg tggagatcaa acgtgcggcc gcacccagcg tgttcatctt ccccccctcc 360 gacgagcagc tgaagagcgg caccgccagc gtggtgtgcc tgctgaacaa cttctacccc 420 cgggaggcca aggtgcagtg gaaggtggac aacgccctgc agagcggcaa cagccaggag 480 agcgtgaccg agcaggacag caaggactcc acctacagcc tgagcagcac cctcaccctg 540 agcaaggccg actacgagaa gcacaaggtg tacgcctgcg aggtgaccca ccagggcctg 600 agcagccccg tgaccaagag cttcaaccgg ggcgagtgt 639 SEQ ID N0:97 eTvltqspgtlslspgeratlscrasqrvssylawyqq

KPGQAPRLLIYGASTRAAGIPDRFSGSGSGTDFTLTIS

RLEPEDSAVYYCQQYGRTPLTFGGGTKVEIKRAAAPSV

FIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNA

LQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKV

YACEVTHQGLSSPVTKSFNRGEC SEQ ID NO:98 tcctatgtgc tgactcagcc accctcggtg tcagtggccc caggacagac ggccaggatt 60 acctgtgggg gaaacaacat tggaagtaaa agtgtgcact ggtaccagca gaagccaggc 120 caggcccctg tgctggtcgt ctatgatgat agcgaccggc cctcagggat ccctgagcga 180 ttctctggct ccaactctgg gaacacggcc accctgacca tcagcagggt cgaagccggg 240 gatgaggccg actattactg tcaggtgtgg gatagtagta gtgatcatgc tgtgttcgga 300 ggaggcaccc agctgaccgt cctcggtgcg gccgcaggcc agcccaaggc cgctcccagc 360 gtgaccctgt tccccccctc ctccgaggag ctgcaggcca acaaggccac cctggtgtgc 420 ctcatcagcg acttctaccc tggcgccgtg accgtggcct ggaaggccga cagcagcccc 480 gtgaaggccg gcgtggagac caccaccccc agcaagcaga gcaacaacaa gtacgccgcc 540 agcagctacc tgagcctcac ccccgagcag tggaagagcc accggagcta cagctgccag 600 gtgacccacg agggcagcac cgtggagaag accgtggccc ccaccgagtg cage 654 SEQ ID NO:99

SYVLTQPPSVSVAPGQTARITCGGNNIGSKSVHWYQQK

PGQAPVLVVYDDSDRPSGIPERFSGSNSGNTATLTISR

VEAGDEADYYCQVWDSSSDHAVFGGGTQLTVLGAAAGQ

PKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTV

AWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQ

WKSHRSYSCQVTHEGSTVEKTVAPTECS SEQ ID NO: 100 tcctatgtgc tgactcagcc accctcagcg tctgggaccc ccgggcagag ggtcaccatc 60 tcttgttctg gaagcagctc caacatcgga agtaattatg tatactggta ccagcagctc 120 ccaggcacgg cccccaaact cctcatctat agggatggtc agcggccctc aggggtccct 180 gaeegattet ctggctccaa gtctggcacc tcagcctccc tggccatcag tggactccgg 240 teegatgatg aggetgatta ttactgtgca acatgggatg acaacctgag tggtccagta 300 tteggeggag ggaccaagct gaccgtccta ggtgeggeeg caggccagcc caaggccgct 360 cccagcgtga ccctgttccc cccctcctcc gaggagetge aggccaacaa ggccaccctg 420 gtgtgcctca teagegaett ctaccctggc gccgtgaccg tggcctggaa ggccgacagc 480 agccccgtga aggeeggegt ggagaccacc acccccagca ageagageaa caacaagtac 540 gccgccagca gctacctgag cctcaccccc gagcagtgga agagccaccg gagetaeage 600 tgccaggtga cccacgaggg cagcaccgtg gagaagaeeg tggcccccac egagtgeage 660 SEQ ID NO: 101

S-Y^rLT-QPPSASGTPGQRVTISCSGSSSNIGSNYVYWYQ

QLPGTAPKLLIYRDGQRPSGVPDRFSGSKSGTSASLAI sglrsddeadyycatwddnlsgpvfgggtkltvlgaaa

GQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAV

TVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTP

EQWKSHRSYSCQVTHEGSTVEKTVAPTECS SEQ ID NO: 102 gaaattgtgt tgacccagtc tccaggcacc ctgtctttgt ctccagggga aagagccacc 60 ctctcctgca gggccagtca gagtgttagc ageagetaet tagcctggta ccagcagaaa 120 cctggccagg ctcccaggct cctcatctat ggtgcatcca gcagggccac tggcatccca 180 gaeaggttea gtggcagtgg gtctgggaca gacttcactc tcaccatcag cagactggag 240 cctgaagatt ttgcagtgta ttactgtcag cagtatggta gctcacccag aaetttegge 300 ggagggacca aggtggagat caaacgtgcg gccgcaccca gcgtgttcat cttccccccc 360 tccgacgagc agetgaagag cggcaccgcc agcgtggtgt gcctgctgaa caacttctac 420 ccccgggagg ccaaggtgca gtggaaggtg gacaacgccc tgeagagegg caacagccag 480 gagagegtga ccgagcagga cagcaaggac tccacctaca gcctgagcag caccctcacc 540 ctgagcaagg ccgactacga gaagcacaag gtgtacgcct gegaggtgae ccaccagggc 600 ctgagcagcc ccgtgaccaa gagetteaae cggggcgagt gt 642 SEQ ID NO: 103

EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQ

QKPGQAPRLLIYGASSRATGIPDRFSGSGSGTDFTLTI

SRLEPEDFAVYYCQQYGSSPRTFGGGTKVEIKRAAAPS

VFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDN

ALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHK

VYACEVTHQGLSSPVTKSFNRGEC SEQ ID NO: 104 cagtctgccc tgactcagcc tgcctccgtg tctgggtctc ctggacagtc gatcaccatc 60 tcctgcactg gaaccagcag tgacgttggt ggttataact atgtctcctg gtaccaacag 120 cacccaggca aagcccccaa actcatgatt tatgaggtca gtaatcggcc ctcaggggtt 180 tctaatcgct tctctggctc caagtctggc aacacggcct ccctgaccat ctctgggctc 240, caggctgagg acgaggctga ttattactgc agctcatata caagcagcag cactcttgtc 300 ttcggaactg ggaccaaggt caccgtccta ggtgcggccg caggccagcc caaggccgct 360 cccagcgtga ccctgttccc cccctcctcc gaggagctgc aggccaacaa ggccaccctg 420 gtgtgcctca tcagcgactt ctaccctggc gccgtgaccg tggcctggaa ggccgacagc 480 agccccgtga aggccggcgt ggagaccacc acccccagca agcagagcaa caacaagtac 540 gccgccagca gctacctgag cctcaccccc gagcagtgga agagccaccg gagctacagc 600 tgccaggtga cccacgaggg cagcaccgtg gagaagaccg tggcccccac cgagtgcagc 660 SEQ ID NO: 105

QSALTQPASVSGSPGQSITISCTGTSSDVGGYNYVSWY

QQHPGKAPKLMIYEVSNRPSGVSNRFSGSKSGNTASLT

ISGLQAEDEADYYCSSYTSSSTLVFGTGTKVTVLGAAA

GQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAV

TVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTP

EQWKSHRSYSCQVTHEGSTVEKTVAPTECS SEQ ID NO: 106 cagtctgtcg tgacgcagcc gccctcggtg tcagtggccc caggacagac ggccaggatt 60 acctgtgggg gaaacaacat tggaagtaaa agtgtgcact ggtaccagca gaagccaggc 120 caggcccctg tgctggtcgt ctatgatgat agcgaccggc cctcagggat ccctgagcga 180 ttctctggct ccaactctgg gaacacggcc accctgacca tcagcagggt cgaagccggg 240 gatgaggccg actattactg tcaggtgtgg gatagtagta gtgatcatta tgtcttcgga 300 actgggacca aggtcaccgt cctaggtgcg gccgcaggcc agcccaaggc cgctcccagc 360 gtgaccctgt tccccccctc ctccgaggag ctgcaggcca acaaggccac cctggtgtgc 420 ctcatcagcg acttctaccc tggcgccgtg accgtggcct ggaaggccga cagcagcccc 480 gtgaaggccg gcgtggagac caccaccccc agcaagcaga gcaacaacaa gtacgccgcc 540 agcagctacc tgagcctcac ccccgagcag tggaagagcc accggagcta cagctgccag 600 gtgacccacg agggcagcac cgtggagaag accgtggccc ccaccgagtg cage 654 SEQ ID NO: 107 qsvvtqppsvsvapgqtaritcggnnigsksvhwyqqk pgqapvlvvyddsdrpsgiperfsgsnsgntatltisr veagdeadyycqvwdsssdhyvfgtgtkvtvlgaaagq pkaapsvtlfppsseelqankatlvclisdfypgavtv awkadsspvkagvetttpskqsnnkyaassylsltpeq wkshrsyscqvthegstvektvaptecs SEQ ID NO: 108 actgtgttga cacagccgcc ctcagtgtct ggggccccag ggcagagggt caccatctcc 60 tgcactggga gcagctccaa catcggggca ggttatgatg tacactggta ccagcagctt 120 ccaggaacag cccccaaact cctcatctat ggtaacagca atcggccctc aggggtccct 180 gaccgattct ctggctccaa gtctggcacg tcagccaccc tgggcatcac cggactccag 240 actggggacg aggeegatta ttactgcgga acatgggata gcagcctgag tgcttatgtc 300 ttcggaactg ggaccaaggt caccgtccta ggtgcggccg caggccagcc caaggccgct 360 cccagcgtga ccctgttccc cccctcctcc gaggagctgc aggccaacaa ggccaccctg 420 gtgtgcctca tcagcgactt ctaccctggc gccgtgaccg tggcctggaa ggccgacagc 480 agccccgtga aggccggcgt ggagaccacc acccccagca agcagagcaa caacaagtac 540 gccgccagca gctacctgag cctcaccccc gagcagtgga agagccaccg gagctacagc 600 tgccaggtga cccacgaggg cagcaccgtg gagaagaccg tggcccccac cgagtgcagc 660 SEQ ID NO: 109 tvltqppsvsgapgqrvtisctgsssnigagydvhwyq qlpgtapklliygnsnrpsgvpdrfsgsksgtsatlgi tglqtgdeadyycgtwdsslsayvfgtgtkvtvlgaaa

GQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAV tvawkadsspvkagvetttpskqsnnkyaassylsltp

EQWKSHRSYSCQVTHEGSTVEKTVAPTECS SEQ ID NO:110 mekivllfaivslvksdqicigyhannsteqvdtimek nvtvthaqdilekkhngklcdldgvkplilrdcsvagw

LLGNPMCDEFINVPEWSYIVEKANPVNDLCYPGDFNDY eelkhllsrinhfekiqiipksswssheaslgvssacp yqgkssffrnvvwlikknstyptikrsynntnqedllv lwgihhpndaaeqtklyqnpttyisvgtstlnqrlvpr iatrskvngqsgrmeffwtilkpndainfesngnfiap eyaykivkkgdstimkseleygncntkcqtpmgainss mpfhnihpltigecpkyvksnrlvlatglrnspqrerr rkkrglfgaiagfieggwqgmvdgwygyhhsneqgsgy aadkestqkaidgvtnkvnsiidkmntqfeavgrefnn lerrienlnkkmedgfldvwtynaellvlmenertldf hdsnvknlydkvrlqlrdnakelgngcfefyhkcdnec mesvrngtydypqyseearlkreeisgvklesigiyqi lsiystvasslalaimvaglslwmcsngslqcr SEQ ID NO: 111 mekivllfaivslvksdqicigyhannsteqvdtimek

NVTVTHAQDILEKTHNGKLCDLDGVKPLILRDCSVAGW LLGNPMCDEFINVPEWSYIVEKANPVNDLCYPGDFNDY EELKHLLSRINHFEKIQI I PKSSWSSHEASLGVSSACP YQGKSSFFRNVVWLIKKNSTYPTIKRSYNNTNQEDLLV LWGIHHPNDAAEQTKLYQNPTTYISVGTSTLNQRLVPR IATRSKVNGQSGRMEFFWTILKPNDAINFESNGNFIAP EYAYKIVKKGDSTIMKSELEYGNCNTKCQTPMGAINSS MPFHNIHPLTIGECPKYVKSNRLVLATGLRNSPQRERR

RKKRGLFGAIAGFIEGGWQGMVDGWYGYHHSNEQGSGY

AADKESTQKAIDGVTNKVNSIIDKMNTQFEAVGREFNN

LERRIENLNKKMEDGFLDVWTYNAELLVLMENERTLDF

HDSNVKNLYDKVRLQLRDNAKELGNGCFEFYHKCDNEC

MESVRNGTYDYPQYSEEARLKREEISGVKLESIGIYQI

LSIYSTVASSLALAIMVAGLSLWMCSNGSLQCR SEQ ID NO: 112

MEKIVLLLAIVSLVKSDQICIGYHANNSTEQVDTIMEK NVTVTHAQDI LEKTHNGKLCDLDGVKPL I LRDC SVAGW LLGNPMCDEFINVPEWSYIVEKANPANDLCYPGNFNDY EELKHLLSRINHFEKIQIIPKSSWSDHEASSGVSSACP YQGKSSFFRNVVWLIKKNSSYPTIKRSYNNTNQEDLLV LWGIHHPNDAAEQTRLYQNPTTYISVGTSTLNQRLVPK IATRSKVNGQSGRMEFFWTILKPNDAINFESNGNFIAP EYAYKIVKKGDSAIMKSELEYGNCNTKCQTPMGAINSS MPFHNIHPLTIGECPKYVKSNRLVLATGLRNSPQRERR RKKRGLFGAIAGFIEGGWQGMVDGWYGYHHSNEQGSGY AADKE STQKAI DGVTNKVN S I I DKMNTQFEAVGREFNN LERRIENLNKKMEDGFLDVWTYNAELLVLMENERTLDF HDSNVKNLYDKVRLQLRDNAKELGNGCFEFYHKCDNEC MESVRNGTYDYPQYSEEARLKREEISGVKLESIGIYQI LSIYSTVASSLALAIMVAGLSLWMCSNGSLQCR SEQ ID NO: 113

MEKIVLLFAIVSLVKSDQICIGYHANNSTEQVDTIMEK NVTVTHAQDILEKTHNGKLCDLDGVKPLILRDCSVAGW LLGNPMCDEFINVPEWSYIVEKANPVNDLCYPGDFNDY EELKHLLSRINHFEKIQII PKSSWSSHEASLGVSSACP YQGKSSFFRNVVWL I KKNS TYPT IKRSYNNTNQE DLLV LWGIHHPNDAAEQTKLYQNPTTYISVGTSTLNQRLVPR IATRSKVNGQSGRMEFFWTILKPNDAINFESNGNFIAP EYAYKIVKKGDSTIMKSELEYGNCNTKCQTPMGAINSS MPFHNIHPLTIGECPKYVKSNRLVLATGLRNSPQRERR RKKRGLFGAIAGFIEGGWQGMVDGWYGYHHSNEQGSGY AADKESTQKAIDGVTNKVNSIIDKMNTQFEAVGREFNN LERRIENLNKKMEDGFLDVWTYNAELLVLMENERTLDF HDSNVKNLYDKVRLQLRDNAKELGNGCFEFYHKCDNEC MESVRNGTYDYPQYSEEARLKREEISGVKLESIGIYQI QHSGGRSSLEGPRFEQKLISEEDLNMHTGHHHHHH SEQ ID NO:114

MEKIVLLLAIVSLVKSDQICIGYHANNSTEQVDTIMEK NVTVTHAQDI LEKTHNGKLCDLDGVKPL I LRDC SVAGW LLGNPMCDEFINVPEWSYIVEKANPANDLCYPGNFNDY EELKHLLSRINHFEKIQI I PKSSWSDHEASSGVSSAC P YQGKSSFFRNVVWLIKKNSSYFTIKRSYNNTNQEDLLV LWGIHHPNDAAEQTRLYQNPTTYISVGTSTLNQRLVPK IATRSKVNGQSGRMEFFWTILKPNDAINFESNGNFIAP EYAYKIVKKGDSAIMKSELEYGNCNTKCQTPMGAINSS MPFHNIHPLTIGECPKYVKSNRLVLATGLRNSPQRERR RKKRGLFGAIAGFIEGGWQGMVDGWYGYHHSNEQGSGY AADKESTQKAIDGVTNKVNSIIDKMNTQFEAVGREFNN LERRIENLNKKMEDGFLDVWTYNAELLVLMENERTLDF HDSNVKNLYDKVRLQLRDNAKELGNGCFEFYHKCDNEC MESVRNGTYDYPQYSEEARLKREEISGVKLESIGIYQI QHSGGRSSLEGPRFEQKLISEEDLNMHTGHHHHHH SEQ ID NO:115 gaggtgcagc tggtggagtc tggggctgag gtgaagaagc ctgggtcctc ggtgaaagtc 60 tcttgcaagg cttctggagg ccccttccgc agctatgcta tcagctgggt gcgacaggcc 120 cctggacaag ggcctgagtg gatgggaggg atcatcccta tttttggtac aacaaaatac 180 gcaccgaagt tccagggcag agtcacgatt accgcggacg atttcgcggg cacagtttac 240 atggagctga gcagcctgcg atctgaggac acggccatgt actactgtgc gaaacatatg 300 gggtaccagg tgcgcgaaac tatggacgtc tggggcaaag ggaccacggt caccgtctcg 360 agcggtacgg gcggttcagg cggaaccggc agcggcactg gcgggtcgac gtcctatgtg 420 ctgactcagc caccctcagc gtctgggacc cccgggcaga gggtcaccat ctcttgttct 480 ggaagcacgt tcaacatcgg aagtaatgct gtagactggt accggcagct cccaggaacg 540 gcccccaaac tcctcatcta tagtaataat cagcggccct caggggtccc tgaccgattc 600 tctggctcca ggtctggcac ctcagcctcc ctggccatca gtgggctcca gtctgaggat 660 gaggctgatt attactgtgc agcatgggat gacatcctga atgttccggt attcggcgga 720 gggaccaagc tgaccgtcct aggt 744 SEQ ID NO: 116

EVQLVESGAEVKKPGSSVKVSCKASGGPFRSYAISWVR QAPGQGPEWMGGIIPIFGTTKYAPKFQGRVTITADDFA GTVYMELSSLRSEDTAMYYCAKHMGYQVRETMDVWGKG TTVTVSSGTGGSGGTGSGTGGSTSYVLTQPPSASGTPG QRVTISCSGSTFNIGSNAVDWYRQLPGTAPKLLIYSNN QRPSGVPDRFSGSRSGTSASLAISGLQSEDEADYYCAA WDDI LNVPVFGGGTKLTVLG SEQ ID N0:117 caggtccagc tggtgcagtc tggggctgag gtgaagaagc ctgggtcctc ggtgaaagtc 60 tcttgcaagg cttctggagg ccccttccgc agctatgcta tcagctgggt gcgacaggcc 120 cctggacaag ggcctgagtg gatgggaggg atcatcccta tttttggtac aacaaaatac 180 gcaccgaagt tccagggcag agtcacgatt accgcggacg atttcgcggg cacagtttac 240 atggagctga gcagcctgcg atctgaggac acggccatgt actactgtgc gaaacatatg 300 gggtaccagg tgcgcgaaac tatggacgtc tggggcaaag ggaccacggt caccgtctcg 360 agcggtacgg gcggttcagg cggaaccggc agcggcactg gcgggtcgac gcagtctgcc 420 ctgactcagc ctgccgccgt gtctgggtct cctggacagt cgatcaccat ctcctgcact 480 ggaaccagca gtgacgttgg tggttataac tatgtctcct ggtaccaaca gcacccaggc 540 aaagcccoca aactcatgat ttatgaggtc agtaatcggc cctcaggggt ttctaatcgc 600 ttctctggct ccaagtctgg caacacggcc tccctgacca tctctgggct ccaggctgag 660 gacgaggctg attattactg cagctcatat acaagcagca gcacttatgt cttcggaact 720 gggaccaagg tcaccgtcct aggt 744 SEQ ID NO:118

QVQLVQSGAEVKKPGSSVKVSCKASGGPFRSYAISWVR Q A P G Q G PEWMGGI I PIFGTTKYAPKFQGRVTI TADDFA GTVYMELSSLRSEDTAMYYCAKHMGYQVRETMDVWGKG TTVTVSSGTGGSGGTGSGTGGSTQSALTQPAAVSGSPG QSITISCTGTSSDVGGYNYVSWYQQHPGKAPKLMIYEV SNRPSGVSNRFSGSKSGNTASLTISGLQAEDEADYYCS SYTSSSTYVFGTGTKVTVLG SEQ ID NO:119 gaggtgcagc tggtggagtc tggggctgag gtgaagaagc ctgggtcctc ggtgaaagtc 60 tcttgcaagg cttctggagg ccccttccgc agctatgcta tcagctgggt gcgacaggcc 120 cctggacaag ggcctgagtg gatgggaggg atcatcccta tttttggtac aacaaaatac 180 gcaccgaagt tccagggcag agtcacgatt accgcggacg atttcgcggg cacagtttac 240 atggagctga gcagcctgcg atctgaggac acggccatgt actactgtgc gaaacatatg 300 gggtaccagg tgcgcgaaac tatggacgtc tggggcaaag ggaccacggt caccgtctcg 360 agcggtacgg gcggttcagg cggaaccggc agcggcactg gcgggtcgac gtcctatgtg 420 ctgactcagc caccctcagt ctctgggacc cccgggcaga gggtcaccat ctcttgctct 480 ggaagccgct ccaacgtcgg agataattct gtatattggt atcaacacgt cccagaaatg 540 gcccccaaac tcctcgtcta taagaatact caacggccct caggagtccc tgcccggttt 600 tccggctcca agtctggcac ttcagcctcc ctggccatca ttggcctcca gtccggcgat 660 gaggctgatt attattgtgt ggcatgggat gacagcgtag atggctatgt cttcggatct 720 gggaccaagg tcaccgtcct aggt 744 SEQ ID NQ:120

EVQLVESGAEVKKPGSSVKVSCKASGGPFRSYAISWVR QAPGQGPEWMGGI I PI FGTTKYAPKFQGRVT ITADDFA GTVYMELSSLRSEDTAMYYCAKHMGYQVRETMDVWGKG TTVTVSSGTGGSGGTGSGTGGSTSYVLTQPPSVSGTPG QRVTISCSGSRSNVGDNSVYWYQHVPEMAPKLLVYKNT QRPSGVPARFSGSKSGTSASLAIIGLQSGDEADYYCVA WDDSVDGYVFGSGTKVTVLG SEQ ID NO: 121 gaggtgcagc tggtggagtc tggggctgag gtgaagaagc ctgggtcctc ggtgaaagtc 60 tcttgcaagg cttctggagg ccccttccgc agctatgcta tcagctgggt gcgacaggcc 120 cctggacaag ggcctgagtg gatgggaggg atcatcccta tttttggtac aacaaaatac 180 gcaccgaagt tccagggcag agtcacgatt accgcggacg atttcgcggg cacagtttac 240 atggagctga gcagcctgcg atctgaggac acggccatgt actactgtgc gaaacatatg 300 gggtaccagg tgcgcgaaac tatggacgtc tggggcaaag ggaccacggt caccgtctcg 360 agcggtacgg gcggttcagg cggaaccggc agcggcactg gcgggtcgac gcagtctgtg 420 ttgacgcagc cgccctcagt gtctgcggcc ccaggacaga aggtcaccat ctcctgctct 480 ggaagcagct ccaacattgg gaatgattat gtatcctggt accagcagct cccaggaaca 540 gcccccaaac tcctcattta tgacaataat aagcgaccct cagggattcc tgaccgattc 600 tctggctcca agtctggcac gtcagccacc ctgggcatca ccggactcca gactggggac 660 gaggccaact attactgcgc aacatgggat cgccgcccga ctgcttatgt tgtcttcggc 720 ggagggacca agctgaccgt cctaggt 747 SEQ ID NO:122

EVQLVESGAEVKKPGSSVKVSCKASGGPFRSYAISWVR Q,A PGQGPEWMGGIIPIFGTTKYAPKFQGRVTITADDFA GTVYMELSSLRSEDTAMYYCAKHMGYQVRETMDVWGKG TTVTVSSGTGGSGGTGSGTGGSTQSVLTQPPSVSAAPG QKVTISCSGSSSNIGNDYVSWYQQLPGTAPKLLIYDNN KRPSGIPDRFSGSKSGTSATLGITGLQTGDEANYYCAT WDRRPTAYVVFGGGTKLTVLG SEQ ID NO:123 caggtacagc tgcagcagtc aggggctgag gtgaagaagc ctgggtcctc ggtgaaggtc 60 tcctgcaagg tttccggagt cattttcagc ggcagtgcga tcagctgggt gcgacaggcc 120 cctggacaag gccttgagtg gatgggaggg atcagccctc tctttggcac aacaaattac 180 gcacaaaagt tccagggcag agtcacgatt accgcggacc aatccacgaa cacaacctac 240 atggaggtga acagcctgag atatgaggac acggccgtgt atttctgtgc gcgaggtcca 300 aaatattaca gtgagtacat ggacgtctgg ggcaaaggga ccacggtcac cgtctcgagc 360 ggtacgggcg gttcaggcgg aaccggcagc ggcactggcg ggtcgacgga catccagatg 420 acccagtctc catcctccct gtctgcatct gtaggagaca gagtcaccat cacttgccgg 480 gcgagtcagg gcattagcag ttatttagcc tggtatcagc agaagccagg gaaagttcct 540 acactcctga tctatgatgc atccactttg cgatcagggg tcccatctcg cttcagtggc 600 agtggatctg cgacagattt cactctcacc atcagcagcc tgcagcctga agatgttgca 660 acttattact gtcaaaggta taacagtgcc cccccgatca ccttcggcca agggacacga 720 ctggagatta aacgt 735 SEQ ID NO: 124

QVQLQQSGAEVKKPGS SVKVSCKVSGVI FSGSAI SWVR QAPGQGLEWMGGISPLFGTTNYAQKFQGRVTITADQST NTTYMEVNSLRYEDTAVYFCARGPKYYSEYMDVWGKGT TVTVSSGTGGSGGTGSGTGGSTDIQMTQSPSSLSASVG DRVTITCRASQGISSYLAWYQQKPGKVPTLLIYDASTL RSGVPSRFSGSGSAT DFTLT I SSLQPEDVATYYCQRYN SAPPITFGQGTRLEIKR SEQ ID NO:125 caggtccagc tggtacagtc tggggctgag gtgaagaagc ctgggtcctc ggtgaaggtc 60 tcctgcaagg cttctggagg caccttcagt agttatgcta tcagctgggt gcgacaggcc 120 cctggacaag ggcttgagtg gatgggagga atcatgggta tgtttggcac aactaactac 180 gcacagaagt tccagggcag agtcacgatt accgcggacg aattcacgag cgcagcctac 240 atggagctga ggagcctgag atctgaggac acggccgtct actactgtgc gaggtctagt 300 ggttattacc ccgaatactt ccaggactgg ggccagggca ccctggtcac cgtctcgagc 360 ggtacgggcg gttcaggcgg aaccggcagc ggcactggcg ggtcgacgca gtctgtgctg 420 actcagccac cctcagagtc cgtgtcccca ggacagacag ccagcgtcac ctgctctgga 480 cataaattgg gggataaata tgtttcgtgg tatcagcaga agccaggcca gtcccctgta 540 ttactcatct atcaagataa caggcggccc tcagggatcc ctgagcgatt cataggctcc 600 aactctggga acacagccac tctgaccatc agcgggaccc aggctctgga tgaggctgac 660 tattactgtc aggcgtggga cagcagcact gcggttttcg gcggagggac caagctgacc 720 gtcctaggt 729 SEQ ID NO:126

QVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYAISWVR

QAPGQGLEWMGGIMGMFGTTNYAQKFQGRVTITADEFT

SAAYMELRSLRSEDTAVYYCARSSGYYPEYFQDWGQGT

LVTVSSGTGGSGGTGSGTGGSTQSVLTQPPSESVSPGQ

TASVTCSGHKLGDKYVSWYQQKPGQSPVLLIYQDNRRP

SGIPERFIGSNSGNTATLTISGTQALDEADYYCQAWDS

STAVFGGGTKLTVLG SEQ ID NO:127 caggtccagc tggtgcagtc tgggggaggc ctggtcaagc ctggggggtc cctgagactc 60 tcctgtgcag cctctggatt caccttcagt agctatagca tgaactgggt ccgccaggct 120 ccagggaagg ggctggagtg ggtctcatcc attagtagta gtagtagtta catatactac 180 gtagactcag tgaagggccg attcaccatc tccagagaca acgccaagaa ctcactgtat 240 ctgcaaatga acagcctgag agccgaggac acggctgtgt attactgtgc gagaggtggt 300 gggagctacg gggcctacga aggctttgac tactggggcc agggcaccct ggtcaccgtc 360 tcgagcggta cgggcggttc aggcggaacc ggcagcggca ctggcgggtc gacggaaatt 420 gtgctgactc agtctccagg caccctgtct ttgtctccag gggaaagagc caccctctcc 480 tgcagggcca gtcagcgtgt tagcagctac ttagcctggt accaacagaa acctggccag 540 gctcccaggc tcctcatcta tggtgcatcc accagggccg ctggcatccc agacaggttc 600 agtggcagtg ggtctgggac agacttcact ctcaccatca gcagactgga gcctgaagat 660 tctgcagtgt attactgtca gcagtatggt aggacaccgc tcactttcgg cggagggacc 720 aaggtggaga tcaaacgt 738 SEQ ID NO:128

QVQLVQSGGGLVKPGGSLRLSCAASGFTFSSYSMNWVR qapgkglewvssisssssyiyyvdsvkgrftisrdnak nslylqmnslraedtavyycargggsygayegfdywgq gtlvtvssgtggsggtgsgtggsteivltqspgtlsls pgeratlscrasqrvssylawyqqkpgqaprlliygas traagipdrfsgsgsgtdftltisrlepedsavyycqq ygrtpltfgggtkveikr SEQ ID NO:129 gaggtgcagc tggtggagtc tggggctgag gtgaagaagc ctgggtcctc ggtgaaagtc 60 tcttgcaagg cttctggagg ccccttccgc agctatgcta tcagctgggt gcgacaggcc 120 cctggacaag ggcctgagtg gatgggaggg atcatcccta tttttggtac aacaaaatac 180 gcaccgaagt tccagggcag agtcacgatt accgcggacg atttcgcggg cacagtttac 240 atggagctga gcagcctgcg atctgaggac acggccatgt actactgtgc gaaacatatg 300 gggtaccagg tgcgcgaaac tatggacgtc tggggcaaag ggaccacggt caccgtctcg 360 agcggtacgg gcggttcagg cggaaccggc agcggcactg gcgggtcgac gtcctatgtg 420 ctgactcagc caccctcggt gtcagtggcc ccaggacaga cggccaggat tacctgtggg 480 ggaaacaaca ttggaagtaa aagtgtgcac tggtaccagc agaagccagg ccaggcccct 540 gtgctggtcg tctatgatga tagcgaccgg ccctcaggga tccctgagcg attctctggc 600 tccaactctg ggaacacggc caccctgacc atcagcaggg tcgaagccgg ggatgaggcc 660 gactattact gtcaggtgtg ggatagtagt agtgatcatg ctgtgttcgg aggaggcacc 720 cagctgaccg tcctcggt 738 SEQ ID NO: 130

EVQLVESGAEVKKPGSSVKVSCKASGGPFRSYAISWVR QAPGQGPEWMGG I I P I FGTTKYAPKFQGRVT I TADDFA GTVYMELSSLRSEDTAMYYCAKHMGYQVRETMDVWGKG TTVTVSSGTGGSGGTGSGTGGSTSYVLTQPPSVSVAPG QTARITCGGNNIGSKSVHWYQQKPGQAPVLVVYDDSDR PSGIPERFSGSNSGNTATLTISRVEAGDEADYYCQVWD SSSDHAVFGGGTQLTVLG SEQ ID NO: 131 gaggtgcagc tggtggagtc tggggctgag gtgaagaagc ctgggtcctc ggtgaaagtc 60 tcttgcaagg cttctggagg ccccttccgc agctatgcta tcagctgggt gcgacaggcc 120 cctggacaag ggcctgagtg gatgggaggg atcatcccta tttttggtac aacaaaatac 180 gcaccgaagt tccagggcag agtcacgatt accgcggacg atttcgcggg cacagtttac 240 atggagctga gcagcctgcg atctgaggac acggccatgt actactgtgc gaaacatatg 300 gggtaccagg tgcgcgaaac tatggacgtc tggggcaaag ggaccacggt caccgtctcg 360 agcggtacgg gcggttcagg cggaaccggc agcggcactg gcgggtcgac gtcctatgtg 420 ctgactcagc caccctcagc gtctgggacc cccgggcaga gggtcaccat ctcttgttct 480 ggaagcagct ccaacatcgg aagtaattat gtatactggt accagcagct cccaggcacg 540 gcccccaaac tcctcatcta tagggatggt cagcggccct caggggtccc tgaccgattc 600 tctggctcca agtctggcac ctcagcctcc ctggccatca gtggactccg gtccgatgat 660 gaggctgatt attactgtgc aacatgggat gacaacctga gtggtccagt attcggcgga 720 gggaccaagc tgaccgtcct aggt 744 SEQ ID NO:132

EVQLVESGAEVKKPGSSVKVSCKASGGPFRSYAISWVR

QAPGQGPEWMGGIIPIFGTTKYAPKFQGRVTITADDFA

GTVYMELSSLRSEDTAMYYCAKHMGYQVRETMDVWGKG

TTVTVSSGTGGSGGTGSGTGGSTSYVLTQPPSASGTPG

QRVTISCSGSSSNIGSNYVYWYQQLPGTAPKLLIYRDG

QRPSGVPDRFSGSKSGTSASLAISGLRSDDEADYYCAT

WDDNLSGPVFGGGTKLTVLG SEQ ID NO:133 gaggtgcagc tggtggagtc tggggctgag gtgaagaagc cagggtcctc ggtgaaggtc 60 tcctgtaagg cctctggagg caccttctcc agctatggta tcagctgggt gcgacaggcc 120 cctggacaag ggcttgagtg gatgggagac atcatcggta tgtttggttc aacaaactac 180 gcacagaact tccagggcag actcacgatt accgcggacg aatccacgag cacagcctac 240 atggagctga gcagcctgag atctgaggac acggccgtgt attactgtgc gagaagtagt 300 ggttattacc ctgcatacct cccccactgg ggccagggca ccttggtcac cgtctcgagc 360 ggtacgggcg gttcaggcgg aaccggcagc ggcactggcg ggtcgacgga aattgtgttg 420 acccagtctc caggcaccct gtctttgtct ccaggggaaa gagccaccct ctcctgcagg 480 gccagtcaga gtgttagcag cagctactta gcctggtacc agcagaaacc tggccaggct 540 cccaggctcc tcatctatgg tgcatccagc agggccactg gcatcccaga caggttcagt 600 ggcagtgggt ctgggacaga cttcactctc accatcagca gactggagcc tgaagatttt 660 gcagtgtatt actgtcagca gtatggtagc tcacccagaa ctttcggcgg agggaccaag 720 gtggagatca aacgt 735 SEQ ID NO: 134

EVQLVESGAEVKKPGSSVKVSCKASGGTFSSYGISWVR

QAPGQGLEWMGDIIGMFGSTNYAQNFQGRLTITADEST

STAYMELSSLRSEDTAVYYCARSSGYYPAYLPHWGQGT

LVTVSSGTGGSGGTGSGTGGSTEIVLTQSPGTLSLSPG

ERATLSCRASQSVSSSYLAWYQQKPGQAPRLLIYGASS

RATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQY

GSSPRTFGGGTKVEIKR SEQ ID NO:135 gaggtgcagc tggtggagtc tggggctgag gtgaagaagc cggggtcctc ggtgaaggtc 60 tcctgcaagg cttctggagg caccttcagc ttctattcta tgagctgggt gcgacaggcc 120 cctggacaag gacttgagtg gatgggaggg atcatcccta tgtttggtac aacaaactac 180 gcacagaagt tccagggcag agtcacgatt accgcggtcg aatccacgag cacagcctac 240 atggaggtga gcagcctgag atctgaggac acggccgttt attactgtgc gagaggtgat 300 aagggtatct actactacta catggacgtc tggggcaaag ggaccacggt caccgtctcg 360 agcggtacgg gcggttcagg cggaaccggc agcggcactg gcgggtcgac gcagtctgcc 420 ctgactcagc ctgcctccgt gtctgggtct cctggacagt cgatcaccat ctcctgcact 480 ggaaccagca gtgacgttgg tggttataac tatgtctcct ggtaccaaca gcacccaggc 540 aaagccccca aactcatgat ttatgaggtc agtaatcggc cctcaggggt ttctaatcgc 600 ttctctggct ccaagtctgg caacacggcc tccctgacca tctctgggct ccaggctgag 660 gacgaggctg attattactg cagctcatat acaagcagca gcactcttgt cttcggaact 720 gggaccaagg tcaccgtcct aggt 744 SEQ ID NO:136

EVQLVESGAEVKKPGSSVKVSCKASGGTFSFYSMSWVR

QAPGQGLEWMGGIIPMFGTTNYAQKFQGRVTITAVEST

STAYMEVSSLRSEDTAVYYCARGDKGIYYYYMDVWGKG

TTVTVSSGTGGSGGTGSGTGGSTQSALTQPASVSGSPG

QSITISCTGTSSDVGGYNYVSWYQQHPGKAPKLMIYEV

SNRPSGVSNRFSGSKSGNTASLTISGLQAEDEADYYCS

SYTSSSTLVFGTGTKVTVLG SEQ ID NO:137 gaggtgcagc tggtggagtc tggggctgag gtgaagaagc ctgggtcctc ggtgaaggtc 60 tcctgcaagg cttctggagg caccttcagc agctatgcta tcagctgggt gcgacaggcc 120 cctggacaag ggcttgagtg gatgggaggg atcatcggta tgttcggtac agcaaactac 180 gcacagaagt tccagggcag agtcacgatt accgcggacg aatttacgag cacagcctac 240 atggagctga gcagcetgag atctgaggac acggccgtgt attactgtgc gagaggaaat 300 tattactatg agagtagtct cgactactgg ggccagggaa ccctggtcac cgtctcgagc 360 ggtacgggcg gttcaggcgg aaccggcagc ggcactggcg ggtcgacgca gtctgtcgtg 420 acgcagccgc cctcggtgtc agtggcccca ggacagacgg ccaggattac ctgtggggga 480 aacaacattg gaagtaaaag tgtgcactgg taccagcaga agccaggcca ggcccctgtg 540 ctggtcgtct atgatgatag cgaccggccc tcagggatcc ctgagcgatt ctctggctcc 600 aactctggga acacggccac cctgaccatc agcagggtcg aagccgggga tgaggccgac 660 tattactgtc aggtgtggga tagtagtagt gatcattatg tcttcggaac tgggaccaag 720 gtcaccgtcc taggt 735 SEQ ID NO:138

EVQLVESGAEVKKPGSSVKVSCKASGGTFSSYAISWVR qapgqglewmggiigmfgtanyaqkfqgrvtitadeft

STAYMELSSLRSEDTAVYYCARGNYYYESSLDYWGQGT lvtvssgtggsggtgsgtggstqsvvtqppsvsvapgq taritcggnnigsksvhwyqqkpgqapvlvvyddsdrp sgiperfsgsnsgntatltisrveagdeadyycqvwds ssdhyvfgtgtkvtvlg SEQ ID NO:139 caggtgcagc tggtgcagtc tggggctgag gtgaagaagc ctgggtcctc ggtgagagtc 60 tcctgcaagg cttctggaag catcttcaga aactatgcta tgagctgggt gcgacaggcc 120 cctggacaag ggcttgagtg gatgggaggg atcatcgcta tttttgggac accaaagtac 180 gcacagaagt tccagggcag agtcacgatt accgcggacg aatcgacgag cactgtctac 240 atggaactga gcggactgag atctgaggac acggccatgt attactgtgc gaggattccc 300 cactataatt ttggttcggg gagttatttc gactactggg gccagggaac cctggtcacc 360 gtctcgagcg gtacgggcgg ttcaggcgga accggcagcg gcactggcgg gtcgacgact 420 gtgttgacac agccgccctc agtgtctggg gccccagggc agagggtcac catctcctgc 480 actgggagca gctccaacat cggggcaggt tatgatgtac actggtacca gcagcttcca 540 ggaacagccc ccaaactcct catctatggt aacagcaatc ggccctcagg ggtccctgac 600 cgattctctg gctccaagtc tggcacgtca gccaccctgg gcatcaccgg actccagact 660 ggggacgagg ccgattatta ctgcggaaca tgggatagca gcctgagtgc ttatgtcttc 720 ggaactggga ccaaggtcac cgtcctaggt 750

SEQ ID NO:14Q qvqlvqsgaevkkpgssvrvsckasgsifrnyamswvr qapgqglewmggiiaifgtpkyaqkfqgrvtitadest stvymelsglrsedtamyycariphynfgsgsyfdywg qgtlvtvssgtggsggtgsgtggsttvltqppsvsgap gqrvtisctgsssnigagydvhwyqqlpgtapklliyg nsnrpsgvpdrfsgsksgtsatlgitglqtgdeadyyc gtwdsslsayvfgtgtkvtvlg SEQ ID NO:141 tcgacggatc gggagatctc ccgatcccct atggtgcact ctcagtacaa tctgctctga 60 tgccgcatag ttaagccagt atctgctccc tgcttgtgtg ttggaggtcg ctgagtagtg 120 cgcgagcaaa atttaagcta caacaaggca aggcttgacc gacaattgca tgaagaatct 180 gcttagggtt aggcgttttg cgctgcttcg ctaggtggtc aatattggcc attagccata 240 ttattcattg gttatatagc ataaatcaat attggctatt ggccattgca tacgttgtat 300 ccatatcata atatgtacat ttatattggc tcatgtccaa cattaccgcc atgttgacat 360 tgattattga ctagttatta atagtaatca attacggggt cattagttca tagcccatat 420 atggagttcc gcgttacata acttacggta aatggcccgc ctggctgacc gcccaacgac 480 ccccgcccat tgacgtcaat aatgacgtat gttcccatag taacgccaat agggactttc 540 cattgacgtc aatgggtgga gtatttacgg taaactgccc acttggcagt acatcaagtg 600 tatcatatgc caagtacgcc ccctattgac gtcaatgacg gtaaatggcc cgcctggcat 660 tatgcccagt acatgacctt atgggacttt cctacttggc agtacatcta cgtattagtc 720 atcgctatta ccatggtgat gcggttttgg cagtacatca atgggcgtgg atagcggttt 780 gactcacggg gatttccaag tctccacccc attgacgtca atgggagttt gttttggcac 840 caaaatcaac gggactttcc aaaatgtcgt aacaactccg ccccattgac gcaaatgggc 900 ggtaggcgtg tacggtggga ggtctatata agcagagctc gtttagtgaa ccgtcagatc 960 gcctggagac gccatccacg ctgttttgac ctccatagaa gacaccggga ccgatccagc 1020 ctccgcggcc gggaacggtg cattggaagc tggcctggat atcctgactc tcttaggtag 1080 ccttgcagaa gttggtcgtg aggcactggg caggtaagta tcaaggttac aagacaggtt 1140 taaggagatc aatagaaact gggcttgtcg agacagagaa gactcttgcg tttctgatag 1200 gcacctattg gtcttactga catccacttt gcctttctct ccacaggtgt ccactcccag 1260 ttcaattaca gctcgccacc atgggatgga gctgtatcat cctcttcttg gtactgctgc 1320 tggcccagcc ggccagtgac cttgaccggt gcaccacttt tgatgatgtt caagctccta 1380 attacactca acatacttca tctatgaggg gggtttacta tcctgatgaa atttttagat 1440 cggacactct ttatttaact caggatttat ttcttccatt ttattctaat gttacagggt 1500 ttcatactat taatcatacg tttggcaacc ctgtcatacc ttttaaggat ggtatttatt 1560 ttgctgccac agagaaatca aatgttgtcc gtggttgggt ttttggttct accatgaaca 1620 acaagtcaca gtcggtgatt attattaaca attctactaa tgttgttata cgagcatgta 1680 actttgaatt gtgtgacaac cctttctttg ctgtttctaa acccatgggt acacagacac 1740 atactatgat attcgataat gcatttaatt gcactttcga gtacatatct gatgcctttt 1800 cgcttgatgt ttcagaaaag tcaggtaatt ttaaacactt acgagagttt gtgtttaaaa 1860 ataaagatgg gtttctctat gtttataagg gctatcaacc tatagatgta gttcgtgatc 1920 taccttctgg ttttaacact ttgaaaccta tttttaagtt gcctcttggt attaacatta 1980 caaattttag agccattctt acagcctttt cacctgctca agacatttgg ggcacgtcag 2040 ctgcagccta ttttgttggc tatttaaagc caactacatt tatgctcaag tatgatgaaa 2100 atggtacaat cacagatgct gttgattgtt ctcaaaatcc acttgctgaa ctcaaatgct 2160 ctgttaagag ctttgagatt gacaaaggaa tttaccagac ctctaatttc agggttgttc 2220 cctcaggaga tgttgtgaga ttccctaata ttacaaactt gtgtcctttt ggagaggttt 2280 ttaatgctac taaattccct tctgtctatg catgggagag aaaaaaaatt tctaattgtg 2340 ttgctgatta ctctgtgctc tacaactcaa catttttttc aacctttaag tgctatggcg 2400 tttctgccac taagttgaat gatctttgct tctccaatgt ctatgcagat tcttttgtag 2460 tcaagggaga tgatgtaaga caaatagcgc caggacaaac tggtgttatt gctgattata 2520 attataaatt gccagatgat ttcatgggtt gtgtccttgc ttggaatact aggaacattg 2580 atgctacttc aactggtaat tataattata aatataggta tcttagacat ggcaagctta 2640 ggccctttga gagagacata tctaatgtgc ctttctcccc tgatggcaaa ccttgcaccc 2700 cacctgctct taattgttat tggccattaa atgattatgg tttttacacc actactggca 2760 ttggctacca accttacaga gttgtagtac tttcttttga acttttaaat gcaccggcca 2820 cggtttgtgg accaaaatta tccactgacc ttattaagaa ccagtgtgtc aattttaatt 2880 ttaatggact cactggtact ggtgtgttaa ctccttcttc aaagagattt caaccatttc 2940 aacaatttgg ccgtgatgtt tctgatttca ctgattccgt tcgagatcct aaaacatctg 3000 aaatattaga catttcacct tgctcttttg ggggtgtaag tgtaattaca cctggaacaa 3060 atgcttcatc tgaagttgct gttctatatc aagatgttaa ctgcactgat gtttctacag 3120 caattcatgc agatcaactc acaccagctt ggcgcatata ttctactgga aacaatgtat 3180 tccagactca ggcaggctgt cttataggag ctgagcatgt cgacacttct tatgagtgcg 3240 acattcctat tggagctggc atttgtgcta gttaccatac agtttcttta ttacgtagta 3300 ctagccaaaa atctattgtg gcttatacta tgtctttagg tgctgatagt tcaattgctt 3360 actctaataa caccattgct atacctacta acttttcaat tagcattact acagaagtaa 3420 tgcctgtttc tatggctaaa acctccgtag attgtaatat gtacatctgc ggagattcta 3480 ctgaatgtgc taatttgctt ctccaatatg gtagcttttg cacacaacta aatcgtgcac 3540 tctcaggtat tgctgctgaa caggatcgca acacacgtga agtgttcgct caagtcaaac 3600 aaatgtacaa aaccccaact ttgaaatatt ttggtggttt taatttttca caaatattac 3660 ctgaccctct aaagccaact aagaggtctt ttattgagga cttgctcttt aataaggtga 3720 cactcgctga tgctggcttc atgaagcaat atggcgaatg cctaggtgat attaatgcta 3780 gagatctcat ttgtgcgcag aagttcaatg gacttacagt gttgccacct ctgctcactg 3840 atgatatgat tgctgcctac actgctgctc tagttagtgg tactgccact gctggatgga 3900 catttggtgc tggcgctgct cttcaaatac cttttgctat gcaaatggca tataggttca· 3960 atggcattgg agttacccaa aatgttctct atgagaacca aaaacaaatc gccaaccaat 4020 ttaacaaggc gattagtcaa attcaagaat cacttacaac aacatcaact gcattgggca 4080 agctgcaaga cgttgttaac cagaatgctc aagcattaaa cacacttgtt aaacaactta 4140 gctctaattt tggtgcaatt tcaagtgtgc taaatgatat cctttcgcga cttgataaag 4200 tcgaggcgga ggtacaaatt gacaggttaa ttacaggcag acttcaaagc cttcaaacct 4260 atgtaacaca acaactaatc agggctgctg aaatcagggc ttctgctaat cttgctgcta 4320 ctaaaatgtc tgagtgtgtt cttggacaat caaaaagagt tgacttttgt ggaaagggct 4380 accaccttat gtccttccca caagcagccc cgcatggtgt tgtcttccta catgtcacgt 4440 atgtgccatc ccaggagagg aacttcacca cagcgccagc aatttgtcat gaaggcaaag 4500 catacttccc tcgtgaaggt gtttttgtgt ttaatggcac ttcttggttt attacacaga 4560 ggaacttctt ttctccacaa ataattacta cagacaatac atttgtctca ggaaattgtg 4620 atgtcgttat tggcatcatt aacaacacag tttatgatcc tctgcaacct gagcttgact 4680 cattcaaaga agagctggac aagtacttca aaaatcatac atcaccagat gttgattttg 4740 gcgacatttc aggcattaac gcttctgtcg tcaacattca aaaagaaatt gaccgcctca 4800 atgaggtcgc taaaaattta aatgaatcac tcattgacct tcaagaactg ggaaaatatg 4860 agcaatatat taaatggcct ctcgacgaac aaaaactcat ctcagaagag gatctgaatg 4920 ctgtgggcca ggacacgcag gaggtcatcg tggtgccaca ctccttgccc tttaaggtgg 4980 tggtgatctc agccatcctg gccctggtgg tgctcaccat catctccctt atcatcctca 5040 tcatgctttg gcagaagaag ccacgttagg cggccgctcg agtgctagca ccaagggccc 5100 cagcgtgttc cccctggccc ccagcagcaa gagcaccagc ggcggcacag ccgccctggg 5160 ctgcctggtg aaggactact tccccgagcc cgtgaccgtg agctggaaca gcggcgcctt 5220 gaccagcggc gtgcacacct tccccgccgt gctgcagagc agcggcctgt acagcctgag 5280 cagcgtggtg accgtgccca gcagcagcct gggcacccag acctacatct gcaacgtgaa 5340 ccacaagccc agcaacacca aggtggacaa acgcgtggag cccaagagct gcgacaagac 5400 ccacacctgc cccccctgcc ctgcccccga gctgctgggc ggaccctccg tgttcctgtt 5460 cccccccaag cccaaggaca ccctcatgat cagccggacc cccgaggtga cctgcgtggt 5520 ggtggacgtg agccacgagg accccgaggt gaagttcaac tggtacgtgg acggcgtgga 5580 ggtgcacaac gccaagacca agccccggga ggagcagtac aacagcacct accgggtggt 5640 gagcgtgctc accgtgctgc accaggactg gctgaacggc aaggagtaca agtgcaaggt 5700 gagcaacaag gccctgcctg cccccatcga gaagaccatc agcaaggcca agggccagcc 5760 ccgggagccc caggtgtaca ccctgccccc cagccgggag gagatgacca agaaccaggt 5820 gtccctcacc tgtctggtga agggcttcta ccccagcgac atcgccgtgg agtgggagag 5880 caacggccag cccgagaaca actacaagac caccccccct gtgctggaca gcgacggcag 5940 cttcttcctg tacagcaagc tcaccgtgga caagagccgg tggcagcagg gcaacgtgtt 6000 cagctgcagc gtgatgcacg aggccctgca caaccactac acccagaaga gcctgagcct 6060 gagccccggc aagtgataat ctagagggcc cgtttaaacc cgctgatcag cctcgactgt 6120 gccttctagt tgccagccat ctgttgtttg cccctccccc gtgccttcct tgaccctgga 6180 aggtgccact cccactgtcc tttcctaata aaatgaggaa attgcatcgc attgtctgag 6240 taggtgtcat tctattctgg ggggtggggt ggggcaggac agcaaggggg aggattggga 6300 agacaatagc aggcatgctg gggatgcggt gggctctatg gcttctgagg cggaaagaac 6360 cagctggggc tctagggggt atccccacgc gccctgtagc ggcgcattaa gcgcggcggg 6420 tgtggtggtt acgcgcagcg tgaccgctac acttgccagc gccctagcgc ccgctccttt 6480 cgctttcttc ccttcctttc tcgccacgtt cgccggcttt ccccgtcaag ctctaaatcg 6540 ggggctccct ttagggttcc gatttagtgc tttacggcac ctcgacccca aaaaacttga 6600 ttagggtgat ggttcacgta gtgggccatc gccctgatag acggtttttc gccctttgac 6660 gttggagtcc acgttcttta atagtggact cttgttccaa actggaacaa cactcaaccc 6720 tatctcggtc tattcttttg atttataagg gattttgccg atttcggcct attggttaaa 6780 aaatgagctg atttaacaaa aatttaacgc gaattaattc tgtggaatgt gtgtcagtta 6840 gggtgtggaa agtccccagg ctccccagca ggcagaagta tgcaaagcat gcatctcaat 6900 tagtcagcaa ccaggtgtgg aaagtcccca ggctccccag caggcagaag tatgcaaagc 6960 atgcatctca attagtcagc aaccatagtc ccgcccctaa ctccgcccat cccgccccta 7020 actccgccca gttccgccca ttctccgccc catggctgac taattttttt tatttatgca 7080 gaggccgagg ccgcctctgc ctctgagcta ttccagaagt agtgaggagg cttttttgga 7140 ggcctaggct tttgcaaaaa gctcccggga gcttgtatat ccattttcgg atctgatcaa 7200 gagacaggat gaggatcgtt tcgcatgatt gaacaagatg gattgcacgc aggttctccg 7260 gccgcttggg tggagaggct attcggctat gactgggcac aacagacaat cggctgctct 7320 gatgccgccg tgttccggct gtcagcgcag gggcgcccgg ttctttttgt caagaccgac 7380 ctgtccggtg ccctgaatga actgcaggac gaggcagcgc ggctatcgtg gctggccacg 7440 acgggcgttc cttgcgcagc tgtgctcgac gttgtcactg aagcgggaag ggactggctg 7500 ctattgggcg aagtgccggg gcaggatctc ctgtcatctc accttgctcc tgccgagaaa 7560 gtatccatca tggctgatgc aatgcggcgg ctgcatacgc ttgatccggc tacctgccca 7620 ttcgaccacc aagcgaaaca tcgcatcgag cgagcacgta ctcggatgga agccggtctt 7680 gtcgatcagg atgatctgga cgaagagcat caggggctcg cgccagccga actgttcgcc 7740 aggctcaagg cgcgcatgcc cgacggcgag gatctcgtcg tgacccatgg cgatgcctgc 7800 ttgccgaata tcatggtgga aaatggccgc ttttctggat tcatcgactg tggccggctg 7860 ggtgtggcgg accgctatca ggacatagcg ttggctaccc gtgatattgc tgaagagctt 7920 ggcggcgaat gggctgaccg cttcctcgtg ctttacggta tcgccgctcc cgattcgcag 7980 cgcatcgcct tctatcgcct tcttgacgag ttcttctgag cgggactctg gggttcgaaa 8040 tgaccgacca agcgacgccc aacctgccat cacgagattt cgattccacc gccgccttct 8100 atgaaaggtt gggcttcgga atcgttttcc gggacgccgg ctggatgatc ctccagcgcg 8160 gggatctcat gctggagttc ttcgcccacc ccaacttgtt tattgcagct tataatggtt 8220 acaaataaag caatagcatc acaaatttca caaataaagc atttttttca ctgcattcta 8280 gttgtggttt gtccaaactc atcaatgtat cttatcatgt ctgtataccg tcgacctcta 8340 gctagagctt ggcgtaatca tggtcatagc tgtttcctgt gtgaaattgt tatccgctca 8400 caattccaca caacatacga gccggaagca taaagtgtaa agcctggggt gcctaatgag 8460 tgagctaact cacattaatt gcgttgcgct cactgcccgc tttccagtcg ggaaacctgt 8520 cgtgccagct gcattaatga atcggccaac gcgcggggag aggcggtttg cgtattgggc 8580 gctcttccgc ttcctcgctc actgactcgc tgcgctcggt cgttcggctg cggcgagcgg 8640 tatcagctca ctcaaaggcg gtaatacggt tatccacaga atcaggggat aacgcaggaa 8700 agaacatgtg agcaaaaggc cagcaaaagg ccaggaaccg taaaaaggcc gcgttgctgg 8760 cgtttttcca taggctccgc ccccctgacg agcatcacaa aaatcgacgc tcaagtcaga 8820 ggtggcgaaa cccgacagga ctataaagat accaggcgtt tccccctgga agctccctcg 8880 tgcgctctcc tgttccgacc ctgccgctta ccggatacct gtccgccttt ctcccttcgg 8940 gaagcgtggc gctttctcat agctcacgct gtaggtatct cagttcggtg taggtcgttc 9000 gctccaagct gggctgtgtg cacgaacccc ccgttcagcc cgaccgctgc gccttatccg 9060 gtaactatcg tcttgagtcc aacccggtaa gacacgactt atcgccactg gcagcagcca 9120 ctggtaacag gattagcaga gcgaggtatg taggcggtgc tacagagttc ttgaagtggt 9180 ggcctaacta cggctacact agaagaacag tatttggtat ctgcgctctg ctgaagccag 9240 ttaccttcgg aaaaagagtt ggtagctctt gatccggcaa acaaaccacc gctggtagcg 9300 gtttttttgt ttgcaagcag cagattacgc gcagaaaaaa aggatctcaa gaagatcctt 9360 tgatcttttc tacggggtct gacgctcagt ggaacgaaaa ctcacgttaa gggattttgg 9420 tcatgagatt atcaaaaagg atcttcacct agatcctttt aaattaaaaa tgaagtttta 9480 aatcaatcta aagtatatat gagtaaactt ggtctgacag ttaccaatgc ttaatcagtg 9540 aggcacctat ctcagcgatc tgtctatttc gttcatccat agttgcctga ctccccgtcg 9600 tgtagataac tacgatacgg gagggcttac catctggccc cagtgctgca atgataccgc 9660 gagacccacg ctcaccggct ccagatttat cagcaataaa ccagccagcc ggaagggccg 9720 agcgcagaag tggtcctgca actttatccg cctccatcca gtctattaat tgttgccggg 9780 aagctagagt aagtagttcg ccagttaata gtttgcgcaa cgttgttgcc attgctacag 9840 gcatcgtggt gtcacgctcg tcgtttggta tggcttcatt cagctccggt tcccaacgat 9900 caaggcgagt tacatgatcc cccatgttgt gcaaaaaagc ggttagctcc ttcggtcctc 9960 cgatcgttgt cagaagtaag ttggccgcag tgttatcact catggttatg gcagcactgc 10020 ataattctct tactgtcatg ccatccgtaa gatgcttttc tgtgactggt gagtactcaa 10080 ccaagtcatt ctgagaatag tgtatgcggc gaccgagttg ctcttgcccg gcgtcaatac 10140 gggataatac cgcgccacat agcagaactt taaaagtgct catcattgga aaacgttctt 10200 Gggggcgaaa actctcaagg atcttaccgc tgttgagatc cagttcgatg taacccactc 10260 gtgcacccaa ctgatcttca gcatctttta ctttcaccag cgtttctggg tgagcaaaaa 10320 caggaaggca aaatgccgca aaaaagggaa taagggcgac acggaaatgt tgaatactca 10380 tactcttcct ttttcaatat tattgaagca tttatcaggg ttattgtctc atgagcggat 10440 acatatttga atgtatttag aaaaataaac aaataggggt tccgcgcaca tttccccgaa 10500 aagtgccacc tgacg 10515 SEQ ID NO: 142 tcgacggatc gggagatctc ccgatcccct atggtgcact ctcagtacaa tctgctctga 60 tgccgcatag ttaagccagt atctgctccc tgcttgtgtg ttggaggtcg ctgagtagtg 120 cgcgagcaaa atttaagcta caacaaggca aggcttgacc gacaattgtt aattaacatg 180 aagaatctgc ttagggttag gcgttttgcg ctgcttcgct aggtggtcaa tattggccat 240 tagccatatt attcattggt tatatagcat aaatcaatat tggctattgg ccattgcata 300 cgttgtatcc atatcataat atgtacattt atattggctc atgtccaaca ttaccgccat 360 gttgacattg attattgact agttattaat agtaatcaat tacggggtca ttagttcata 420 gcccatatat ggagttccgc gttacataac ttacggtaaa tggcccgcct ggctgaccgc 480 ccaacgaccc ccgcccattg acgtcaataa tgacgtatgt tcccatagta acgccaatag 540 ggactttcca ttgacgtcaa tgggtggagt atttacggta aactgcccac ttggcagtac 600 atcaagtgta tcatatgcca agtacgcccc ctattgacgt caatgacggt aaatggcccg 660 cctggcatta tgcccagtac atgaccttat gggactttcc tacttggcag tacatctacg 720 tattagtcat cgctattacc atggtgatgc ggttttggca gtacatcaat gggcgtggat 780 agcggtttga ctcacgggga tttccaagtc tccaccccat tgacgtcaat gggagtttgt 840 tttggcacca aaatcaacgg gactttccaa aatgtcgtaa caactccgcc ccattgacgc 900 aaatgggcgg taggcgtgta cggtgggagg tctatataag cagagctcgt ttagtgaacc 960 gtcagatcgc ctggagacgc catccacgct gttttgacct ccatagaaga caccgggacc 1020 gatccagcct ccgcggccgg gaacggtgca ttggaatcga tgactctctt aggtagcctt 1080 gcagaagttg gtcgtgaggc actgggcagg taagtatcaa ggttacaaga caggtttaag 1140 gagatcaata gaaactgggc ttgtcgagac agagaagact cttgcgtttc tgataggcac 1200 ctattggtct tactgacatc cactttgcct ttctctccac aggtgtccac tcccagttca 1260 attacagctc gccaccatgc ggctgcccgc ccagctgctg ggccttctca tgctgtgggt 1320 gcccgcctcg agatctatcg atgcatgcca tggtaccaag cttgccacca tgagcagcag 1380 ctcttggctg ctgctgagcc tggtggccgt gacagccgcc cagagcacca tcgaggagca 1440 ggccaagacc ttcctggaca agttcaacca cgaggccgag gacctgttct accagagcag 1500 cctggccagc tggaactaca acaccaacat caccgaggag aacgtgcaga acatgaacaa 1560 cgccggcgac aagtggagcg ccttcctgaa ggagcagagc acactggccc agatgtaccc 1620 cctgcaggag atccagaacc tgaccgtgaa gctgcagctg caggccctgc agcagaacgg 1680 cagcagcgtg ctgagcgagg acaagagcaa gcggctgaac accatcctga acaccatgtc 1740 caccatctac agcaccggca aagtgtgcaa ccccgacaac ccccaggagt gcctgctgct 1800 ggagcccggc ctgaacgaga tcatggccaa cagcctggac tacaacgagc ggctgtgggc 1860 ctgggagagc tggcggagcg aagtgggcaa gcagctgcgg cccctgtacg aggagtacgt 1920 ggtgctgaag aacgagatgg ccagggccaa ccactacgag gactacggcg actactggag 1980 aggcgactac gaagtgaacg gcgtggacgg ctacgactac agcagaggcc agctgatcga 2040 ggacgtggag cacaccttcg aggagatcaa gcctctgtac gagcacctgc acgcctacgt 2100 gcgggccaag ctgatgaacg cctaccccag ctacatcagc cccatcggct gcctgcccgc 2160 ccacctgctg ggcgacatgt ggggccggtt ctggaccaac ctgtacagcc tgaccgtgcc 2220 cttcggccag aagcccaaca tcgacgtgac cgacgccatg gtggaccagg cctgggacgc 2280 ccagcggatc ttcaaggagg ccgagaagtt cttcgtgagc gtgggcctgc ccaacatgac 2340 ccagggcttt tgggagaaca gcatgctgac cgaccccggc aatgtgcaga aggccgtgtg 2400 ccaccccacc gcctgggacc tgggcaaggg cgacttccgg atcctgatgt gcaccaaagt 2460 gaccatggac gacttcctga ccgcccacca cgagatgggc cacatccagt acgacatggc 2520 ctacgccgcc cagcccttcc tgctgcggaa cggcgccaac gagggctttc acgaggccgt 2580 gggcgagatc atgagcctga gcgccgccac ccccaagcac ctgaagagca tcggcctgct 2640 gagccccgac ttccaggagg acaacgagac cgagatcaac ttcctgctga agcaggccct 2700 gaccatcgtg ggcaccctgc ccttcaccta catgctggag aagtggcggt ggatggtgtt 2760 taagggcgag atccccaagg accagtggat gaagaagtgg tgggagatga agcgggagat 2820 cgtgggcgtg gtggagcccg tgccccacga cgagacctac tgcgaccccg ccagcctgtt 2880 ccacgtgagc aacgactact ccttcatccg gtactacacc cggaccctgt accagttcca 2940 gttccaggag gccctgtgcc aggccgccaa gcacgagggc cccctgcaca agtgcgacat 3000 cagcaacagc accgaggccg gacagaaact gttcaacatg ctgcggctgg gcaagagcga 3060 gccctggacc ctggccctgg agaatgtggt gggcgccaag aacatgaatg tgcgccccct 3120 gctgaactac ttcgagcccc tgttcacctg gctgaaggac cagaacaaga acagcttcgt 3180 gggctggagc accgactgga gcccctacgc cgaccagagc atcaaagtgc ggatcagcct 3240 gaagagcgcc ctgggcgaca aggcctacga gtggaacgac aacgagatgt acctgttccg 3300 gagcagcgtg gcctatgcca tgcggcagta cttcctgaaa gtgaagaacc agatgatcct 3360 gttcggcgag gaggacgtga gagtggccaa cctgaagccc cggatcagct tcaacttctt 3420 cgtgaccgcc cccaagaacg tgagcgacat catcccccgg accgaagtgg agaaggccat 3480 ccggatgagc cggagccgga tcaacgacgc cttccggctg aacgacaact ccctggagtt 3540 cctgggcatc cagcccaccc tgggccctcc caaccagccc cccgtgagca tctggctgat 3600 cgtgtttggc gtggtgatgg gcgtgatcgt ggtgggaatc gtgatcctga tcttcaccgg 3660 catccgggac cggaagaaga agaacaaggc ccggagcggc gagaacccct acgccagcat 3720 cgatatcagc aagggcgaga acaaccccgg cttccagaac accgacgacg tgcagaccag 3780 cttctgataa tctagaacga gctcgaattc gaagcttctg cagacgcgtc gacgtcatat 3840 ggatccgata tcgccgtggc ggccgcaccc agcgtgttca tcttcccccc ctccgacgag 3900 cagctgaaga gcggcaccgc cagcgtggtg tgcctgctga acaacttcta cccccgggag 3960 gccaaggtgc agtggaaggt ggacaacgcc ctgcagagcg gcaacagcca ggagagcgtg 4020 accgagcagg acagcaagga ctccacctac agcctgagca gcaccctcac cctgagcaag 4080 gccgactacg agaagcacaa ggtgtacgcc tgcgaggtga cccaccaggg cctgagcagc 4140 cccgtgacca agagcttcaa ccggggcgag tgttaataga cttaagttta aaccgctgat 4200 cagcctcgac tgtgccttct agttgccagc catctgttgt ttgcccctcc cccgtgcctt 4260 ccttgaccct ggaaggtgcc actcccactg tcctttccta ataaaatgag gaaattgcat 4320 cgcattgtct gagtaggtgt cattctattc tggggggtgg ggtggggcag gacagcaagg 4380 gggaggattg ggaagacaat agcaggcatg ctggggatgc ggtgggctct atggcttctg 4440 aggcggaaag aaccagctgg ggctctaggg ggtatcccca cgcgccctgt agcggcgcat 4500 taagcgcggc gggtgtggtg gttacgcgca gcgtgaccgc tacacttgcc agcgccctag 4560 cgcccgctcc tttcgctttc ttcccttcct ttctcgccac gttcgccggc tttccccgtc 4620 aagctctaaa tcgggggctc cctttagggt tccgatttag tgctttacgg cacctcgacc 4680 ccaaaaaact tgattagggt gatggttcac gtagtgggcc atcgccctga tagacggttt 4740 ttcgcccttt gacgttggag tccacgttct ttaatagtgg actcttgttc caaactggaa 4800 caacactcaa ccctatctcg gtctattctt ttgatttata agggattttg gccatttcgg 4860 cctattggtt aaaaaatgag ctgatttaac aaaaatttaa cgcgaattaa ttctgtggaa 4920 tgtgtgtcag ttagggtgtg gaaagtcccc aggctcccca gcaggcagaa gtatgcaaag 4980 catgcatctc aattagtcag caaccaggtg tggaaagtcc ccaggctccc cagcaggcag 5040 aagtatgcaa agcatgcatc tcaattagtc agcaaccata gtcccgcccc taactccgcc 5100 catcccgccc ctaactccgc ccagttccgc ccattctccg ccccatggct gactaatttt 5160 ttttatttat gcagaggccg aggccgcctc tgcctctgag ctattccaga agtagtgagg 5220 aggctttttt ggaggcctag gcttttgcaa aaagctcccg ggagcttgta tatccatttt 5280 cggatctgat cagcacgtga tgaaaaagcc tgaactcacc gcgacgtctg tcgagaagtt 5340 tctgatcgaa aagttcgaca gcgtctccga cctgatgcag ctctcggagg gcgaagaatc 5400 tcgtgctttc agcttcgatg taggagggcg tggatatgtc ctgcgggtaa atagctgcgc 5460 cgatggtttc tacaaagatc gttatgttta tcggcacttt gcatcggccg cgctcccgat 5520 tccggaagtg cttgacattg gggaattcag cgagagcctg acctattgca tctcccgccg 5580 tgcacagggt gtcacgttgc aagacctgcc tgaaaccgaa ctgcccgctg ttctgcagcc 5640 ggtcgcggag gccatggatg cgatcgctgc ggccgatctt agccagacga gcgggttcgg 5700 cccattcgga ccacaaggaa tcggtcaata cactacatgg cgtgatttca tatgcgcgat 5760 tgctgatccc catgtgtatc actggcaaac tgtgatggac gacaccgtca gtgcgtccgt 5820 cgcgcaggct ctcgatgagc tgatgctttg ggccgaggac tgccccgaag tccggcacct 5880 cgtgcacgcg gatttcggct ccaacaatgt cctgacggac aatggccgca taacagcggt 5940 cattgactgg agcgaggcga tgttcgggga ttcccaatac gaggtcgcca acatcttctt 6000 ctggaggccg tggttggctt gtatggagca gcagacgcgc tacttcgagc ggaggcatcc 6060 ggagcttgca ggatcgccgc ggctccgggc gtatatgctc cgcattggtc ttgaccaact 6120 ctatcagagc ttggttgacg gcaatttcga tgatgcagct tgggcgcagg gtcgatgcga 6180 cgcaatcgtc cgatccggag ccgggactgt cgggcgtaca caaatcgccc gcagaagcgc 6240 ggccgtctgg accgatggct gtgtagaagt actcgccgat agtggaaacc gacgccccag 6300 cactcgtccg agggcaaagg aatagcacgt gctacgagat ttcgattcca ccgccgcctt 6360 ctatgaaagg ttgggcttcg gaatcgtttt ccgggacgcc ggctggatga tcctccagcg 6420 cggggatctc atgctggagt tcttcgccca ccccaacttg tttattgcag cttataatgg 6480 ttacaaataa agcaatagca tcacaaattt cacaaataaa gcattttttt cactgcattc 6540 tagttgtggt ttgtccaaac tcatcaatgt atcttatcat gtctgtatac cgtcgacctc 6600 tagctagagc ttggcgtaat catggtcata gctgtttcct gtgtgaaatt gttatccgct 6660 cacaattcca cacaacatac gagccggaag cataaagtgt aaagcctggg gtgcctaatg 6720 agtgagctaa ctcacattaa ttgcgttgcg ctcactgccc gctttccagt cgggaaacct 6780 gtcgtgccag ctgcattaat gaatcggcca acgcgcgggg agaggcggtt tgcgtattgg 6840 gcgctcttcc gcttcctcgc tcactgactc gctgcgctcg gtcgttcggc tgcggcgagc 6900 ggtatcagct cactcaaagg cggtaatacg gttatccaca gaatcagggg ataacgcagg 6960 aaagaacatg tgagcaaaag gccagcaaaa ggccaggaac cgtaaaaagg ccgcgttgct 7020 ggcgtttttc cataggctcc gcccccctga cgagcatcac aaaaatcgac gctcaagtca 7080 gaggtggcga aacccgacag gactataaag ataccaggcg tttccccctg gaagctccct 7140 cgtgcgctct cctgttccga ccctgccgct taccggatac ctgtccgcct ttctcccttc 7200 gggaagcgtg gcgctttctc atagctcacg ctgtaggtat ctcagttcgg tgtaggtcgt 7260 tcgctccaag ctgggctgtg tgcacgaacc ccccgttcag cccgaccgct gcgccttatc 7320 cggtaactat cgtcttgagt ccaacccggt aagacacgac ttatcgccac tggcagcagc 7380 cactggtaac aggattagca gagcgaggta tgtaggcggt gctacagagt tcttgaagtg 7440 gtggcctaac tacggctaca ctagaagaac agtatttggt atctgcgctc tgctgaagcc 7500 agttaccttc ggaaaaagag ttggtagctc ttgatccggc aaacaaacca ccgctggtag 7560 cggttttttt gtttgcaagc agcagattac gcgcagaaaa aaaggatctc aagaagatcc 7620 tttgatcttt tctacggggt ctgacgctca gtggaacgaa aactcacgtt aagggatttt 7680 ggtcatgaga ttatcaaaaa ggatcttcac ctagatcctt ttaaattaaa aatgaagttt 7740 taaatcaatc taaagtatat atgagtaaac ttggtctgac agttaccaat gcttaatcag 7800 tgaggcacct atctcagcga tctgtctatt tcgttcatcc atagttgcct gactccccgt 7860 cgtgtagata actacgatac gggagggctt accatctggc cccagtgctg caatgatacc 7920 gcgagaccca cgctcaccgg ctccagattt atcagcaata aaccagccag ccggaagggc 7980 cgagcgcaga agtggtcctg caactttatc cgcctccatc cagtctatta attgttgccg 8040 ggaagctaga gtaagtagtt cgccagttaa tagtttgcgc aacgttgttg ccattgctac 8100 aggcatcgtg gtgtcacgct cgtcgtttgg tatggcttca ttcagctccg gttcccaacg 8160 atcaaggcga gttacatgat cccccatgtt gtgcaaaaaa gcggttagct ccttcggtcc 8220 tccgatcgtt gtcagaagta agttggccgc agtgttatca ctcatggtta tggcagcact 8280 gcataattct cttactgtca tgccatccgt aagatgcttt tctgtgactg gtgagtactc 8340 aaccaagtca ttctgagaat agtgtatgcg gcgaccgagt tgctcttgcc cggcgtcaat 8400 acgggataat accgcgccac atagcagaac tttaaaagtg ctcatcattg gaaaacgttc 8460 ttcggggcga aaactctcaa ggatcttacc gctgttgaga tccagttcga tgtaacccac 8520 tcgtgcaccc aactgatctt cagcatcttt tactttcacc agcgtttctg ggtgagcaaa 8580 aacaggaagg caaaatgccg caaaaaaggg aataagggcg acacggaaat gttgaatact 8640 catactcttc ctttttcaat attattgaag catttatcag ggttattgtc tcatgagcgg 8700 atacatattt gaatgtattt agaaaaataa acaaataggg gttccgcgca catttccccg 8760 aaaagtgcca cctgacg 8777 SEQ ID NO: 143 tcgacggatc gggagatctc ccgatcccct atggtgcact ctcagtacaa tctgctctga 60 tgccgcatag ttaagccagt atctgctccc tgcttgtgtg ttggaggtcg ctgagtagtg 120 cgcgagcaaa atttaagcta caacaaggca aggcttgacc gacaattgtt aattaacatg 180 aagaatctgc ttagggttag gcgttttgcg ctgcttcgct aggtggtcaa tattggccat 240 tagccatatt attcattggt tatatagcat aaatcaatat tggctattgg ccattgcata 300 cgttgtatcc atatcataat atgtacattt atattggctc atgtccaaca ttaccgccat 360 gttgacattg attattgact agttattaat agtaatcaat tacggggtca ttagttcata 420 gcccatatat ggagttccgc gttacataac ttacggtaaa tggcccgcct ggctgaccgc 480 ccaacgaccc ccgcccattg acgtcaataa tgacgtatgt tcccatagta acgccaatag 540 ggactttcca ttgacgtcaa tgggtggagt atttacggta aactgcccac ttggcagtac 600 atcaagtgta tcatatgcca agtacgcccc ctattgacgt caatgacggt aaatggcccg 660 cctggcatta tgcccagtac atgaccttat gggactttcc tacttggcag tacatctacg 720 tattagtcat cgctattacc atggtgatgc ggttttggca gtacatcaat gggcgtggat 780 agcggtttga ctcacgggga tttccaagtc tccaccccat tgacgtcaat gggagtttgt 840 tttggcacca aaatcaacgg gactttccaa aatgtcgtaa caactccgcc ccattgacgc 900 aaatgggcgg taggcgtgta cggtgggagg tctatataag cagagctcgt ttagtgaacc 960 gtcagatcgc ctggagacgc catccacgct gttttgacct ccatagaaga caccgggacc 1020 gatccagcct ccgcggccgg gaacggtgca ttggaatcga tgactctctt aggtagcctt 1080 gcagaagttg gtcgtgaggc actgggcagg taagtatcaa ggttacaaga caggtttaag 1140 gagatcaata gaaactgggc ttgtcgagac agagaagact cttgcgtttc tgataggcac 1200 ctattggtct tactgacatc cactttgcct ttctctccac aggtgtccac tcccagttca 1260 attacagctc gccaccatgc ggttctccgc tcagctgctg ggccttctgg tgctgtggat 1320 tcccggcgtc tcgagatcta tcgatgcatg ccatggtacc aagcttgcca ccatgagcag 1380 cagctcttgg ctgctgctga gcctggtggc cgtgacagcc gcccagagca ccatcgagga 1440 gcaggccaag accttcctgg acaagttcaa ccacgaggcc gaggacctgt tctaccagag 1500 cagcctggcc agctggaact acaacaccaa catcaccgag gagaacgtgc agaacatgaa 1560 caacgccggc gacaagtgga gcgccttcct gaaggagcag agcacactgg cccagatgta 1620 ccccctgcag gagatccaga acctgaccgt gaagctgcag ctgcaggccc tgcagcagaa 1680 cggcagcagc gtgctgagcg aggacaagag caagcggctg aacaccatcc tgaacaccat 1740 gtccaccatc tacagcaccg gcaaagtgtg caaccccgac aacccccagg agtgcctgct 1800 gctggagccc ggcctgaacg agatcatggc caacagcctg gactacaacg agcggctgtg 1860 ggcctgggag agctggcgga gcgaagtggg caagcagctg cggcccctgt acgaggagta 1920 cgtggtgctg aagaacgaga tggccagggc caaccactac gaggactacg gcgactactg 1980 gagaggcgac tacgaagtga acggcgtgga cggctacgac tacagcagag gccagctgat 2040 cgaggacgtg gagcacacct tcgaggagat caagcctctg tacgagcacc tgcacgccta 2100 cgtgcgggcc aagctgatga acgcctaccc cagctacatc agccccatcg gctgcctgcc 2160 cgcccacctg ctgggcgaca tgtggggccg gttctggacc aacctgtaca gcctgaccgt 2220 gcccttcggc cagaagccca acatcgacgt gaccgacgcc atggtggacc aggcctggga 2280 cgcccagcgg atcttcaagg aggccgagaa gttcttcgtg agcgtgggcc tgcccaacat 2340 gacccagggc ttttgggaga acagcatgct gaccgacccc ggcaatgtgc agaaggccgt 2400 gtgccacccc accgcctggg acctgggcaa gggcgacttc cggatcctga tgtgcaccaa 2460 agtgaccatg gacgacttcc tgaccgccca ccacgagatg ggccacatcc agtacgacat 2520 ggcctacgcc gcccagccct tcctgctgcg gaacggcgcc aacgagggct ttcacgaggc 2580 cgtgggcgag atcatgagcc tgagcgccgc cacccccaag cacctgaaga gcatcggcct 2640 gctgagcccc gacttccagg aggacaacga gaccgagatc aacttcctgc tgaagcaggc 2700 cctgaccato gtgggcaccc tgcccttcac ctacatgctg gagaagtggc ggtggatggt 2760 gtttaagggc gagatcccca aggaccagtg gatgaagaag tggtgggaga tgaagcggga 2820 gatcgtgggc gtggtggagc ccgtgcccca cgacgagacc tactgcgacc ccgccagcct 2880 gttccacgtg agcaacgact actccttcat ccggtactac acccggaccc tgtaccagtt 2940 ccagttccag gaggccctgt gccaggccgc caagcacgag ggccccctgc acaagtgcga 3000 catcagcaac agcaccgagg ccggacagaa actgttcaac atgctgcggc tgggcaagag 3060 cgagccctgg accctggccc tggagaatgt ggtgggcgcc aagaacatga atgtgcgccc 3120 cctgctgaac tacttcgagc ccctgttcac ctggctgaag gaccagaaca agaacagctt 3180 cgtgggctgg agcaccgact ggagccccta cgccgaccag agcatcaaag tgcggatcag 3240 cctgaagagc gccctgggcg acaaggccta cgagtggaac gacaacgaga tgtacctgtt 3300 ccggagcagc gtggcctatg ccatgcggca gtacttcctg aaagtgaaga accagatgat 3360 cctgttcggc gaggaggacg tgagagtggc caacctgaag ccccggatca gcttcaactt 3420 cttcgtgacc gcccccaaga acgtgagcga catcatcccc cggaccgaag tggagaaggc 3480 catccggatg agccggagcc ggatcaacga cgccttccgg ctgaacgaca actccctgga 3540 gttcctgggc atccagccca ccctgggccc tcccaaccag ccccccgtga gcatctggct 3600 gatcgtgttt ggcgtggtga tgggcgtgat cgtggtggga atcgtgatcc tgatcttcac 3660 cggcatccgg gaccggaaga agaagaacaa ggcccggagc ggcgagaacc cctacgccag 3720 catcgatatc agcaagggcg agaacaaccc cggcttccag aacaccgacg acgtgcagac 3780 cagcttctga taatctagaa cgagctcgaa ttcgaagctt ctgcagacgc gtcgacgtca 3840 tatggatccg atatcgccgt ggcggccgca ggccagccca aggccgctcc cagcgtgacc 3900 ctgttccccc cctcctccga ggagctgcag gccaacaagg ccaccctggt gtgcctcatc 3960 agcgacttct accctggcgc cgtgaccgtg gcctggaagg ccgacagcag ccccgtgaag 4020 gccggcgtgg agaccaccac ccccagcaag cagagcaaca acaagtacgc cgccagcagc 4080 tacctgagcc tcacccccga gcagtggaag agccaccgga gctacagctg ccaggtgacc 4140 cacgagggca gcaccgtgga gaagaccgtg gcccccaccg agtgcagcta atagacttaa 4200 gtttaaaccg ctgatcagcc tcgactgtgc cttctagttg ccagccatct gttgtttgcc 4260 cctcccccgt gccttccttg accctggaag gtgccactcc cactgtcctt tcctaataaa 4320 atgaggaaat tgcatcgcat tgtctgagta ggtgtcattc tattctgggg ggtggggtgg 4380 ggcaggacag caagggggag gattgggaag acaatagcag gcatgctggg gatgcggtgg 4440 gctctatggc ttctgaggcg gaaagaacca gctggggctc tagggggtat ccccacgcgc 4500 cctgtagcgg cgcattaagc gcggcgggtg tggtggttac gcgcagcgtg accgctacac 4560 ttgccagcgc cctagcgccc gctcctttcg ctttcttccc ttcctttctc gccacgttcg 4620 ccggctttcc ccgtcaagct ctaaatcggg ggctcccttt agggttccga tttagtgctt 4680 tacggcacct cgaccccaaa aaacttgatt agggtgatgg ttcacgtagt gggccatcgc 4740 cctgatagac ggtttttcgc cctttgacgt tggagtccac gttctttaat agtggactct 4800 tgttccaaac tggaacaaca ctcaacccta tctcggtcta ttcttttgat ttataaggga 4860 ttttggccat ttcggcctat tggttaaaaa atgagctgat ttaacaaaaa tttaacgcga 4920 attaattctg tggaatgtgt gtcagttagg gtgtggaaag tccccaggct ccccagcagg 4980 cagaagtatg caaagcatgc atctcaatta gtcagcaacc aggtgtggaa agtccccagg 5040 ctccccagca ggcagaagta tgcaaagcat gcatctcaat tagtcagcaa ccatagtccc 5100 gcccctaact ccgcccatcc cgcccctaac tccgcccagt tccgcccatt ctccgcccca 5160 tggctgacta atttttttta tttatgcaga ggccgaggcc gcctctgcct ctgagctatt 5220 ccagaagtag tgaggaggct tttttggagg cctaggcttt tgcaaaaagc tcccgggagc 5280 ttgtatatcc attttcggat ctgatcagca cgtgatgaaa aagcctgaac tcaccgcgac 5340 gtctgtcgag aagtttctga tcgaaaagtt cgacagcgtc tccgacctga tgcagctctc 5400 ggagggcgaa gaatctcgtg ctttcagctt cgatgtagga gggcgtggat atgtcctgcg 5460 ggtaaatagc tgcgccgatg gtttctacaa agatcgttat gtttatcggc actttgcatc 5520 ggccgcgctc ccgattccgg aagtgcttga cattggggaa ttcagcgaga gcctgaccta 5580 ttgcatctcc cgccgtgcac agggtgtcac gttgcaagac ctgcctgaaa ccgaactgcc 5640 cgctgttctg cagccggtcg cggaggccat ggatgcgatc gctgcggccg atcttagcca 5700 gacgagcggg ttcggcccat tcggaccgca aggaatcggt caatacacta catggcgtga 5760 tttcatatgc gcgattgctg atccccatgt gtatcactgg caaactgtga tggacgacac 5820 cgtcagtgcg tccgtcgcgc aggctctcga tgagctgatg ctttgggccg aggactgccc 5880 cgaagtccgg cacctcgtgc acgcggattt cggctccaac aatgtcctga cggacaatgg 5940 ccgcataaca gcggtcattg actggagcga ggcgatgttc ggggattccc aatacgaggt 6000 cgccaacatc ttcttctgga ggccgtggtt ggcttgtatg gagcagcaga cgcgctactt 6060 cgagcggagg catccggagc ttgcaggatc gccgcggctc cgggcgtata tgctccgcat 6120 tggtcttgac caactctatc agagcttggt tgacggcaat ttcgatgatg cagcttgggc 6180 gcagggtcga tgcgacgcaa tcgtccgatc cggagccggg actgtcgggc gtacacaaat 6240 cgcccgcaga agcgcggccg tctggaccga tggctgtgta gaagtactcg ccgatagtgg 6300 aaaccgacgc cccagcactc gtccgagggc aaaggaatag cacgtgctac gagatttcga 6360 ttccaccgcc gccttctatg aaaggttggg cttcggaatc gttttccggg acgccggctg 6420 gatgatcctc cagcgcgggg atctcatgct ggagttcttc gcccacccca acttgtttat 6480 tgcagcttat aatggttaca aataaagcaa tagcatcaca aatttcacaa ataaagcatt 6540 tttttcactg cattctagtt gtggtttgtc caaactcatc aatgtatctt atcatgtctg 6600 tataccgtcg acctctagct agagcttggc gtaatcatgg tcatagctgt ttcctgtgtg 6660 aaattgttat ccgctcacaa ttccacacaa catacgagcc ggaagcataa agtgtaaagc 6720 ctggggtgcc taatgagtga gctaactcac attaattgcg ttgcgctcac tgcccgcttt 6780 ccagtcggga aacctgtcgt gccagctgca ttaatgaatc ggccaacgcg cggggagagg 6840 cggtttgcgt attgggcgct cttccgcttc ctcgctcact gactcgctgc gctcggtcgt 6900 tcggctgcgg cgagcggtat cagctcactc aaaggcggta atacggttat ccacagaatc 6960 aggggataac gcaggaaaga acatgtgagc aaaaggccag caaaaggcca ggaaccgtaa 7020 aaaggccgcg ttgctggcgt ttttccatag gctccgcccc cctgacgagc atcacaaaaa 7080 tcgacgctca agtcagaggt ggcgaaaccc gacaggacta taaagatacc aggcgtttcc 7140 ccctggaagc tccctcgtgc gctctcctgt tccgaccctg ccgcttaccg gatacctgtc 7200 cgcctttctc ccttcgggaa gcgtggcgct ttctcatagc tcacgctgta ggtatctcag 7260 ttcggtgtag gtcgttcgct ccaagctggg ctgtgtgcac gaaccccccg ttcagcccga 7320 ccgctgcgcc ttatccggta actatcgtct tgagtccaac ccggtaagac acgacttatc 7380 gccactggca gcagccactg gtaacaggat tagcagagcg aggtatgtag gcggtgctac 7440 agagttcttg aagtggtggc ctaactacgg ctacactaga agaacagtat ttggtatctg 7500 cgctctgctg aagccagtta ccttcggaaa aagagttggt agctcttgat ccggcaaaca 7560 aaccaccgct ggtagcggtt tttttgtttg caagcagcag attacgcgca gaaaaaaagg 7620 atctcaagaa gatcctttga tcttttctac ggggtctgac gctcagtgga acgaaaactc 7680 acgttaaggg attttggtca tgagattatc aaaaaggatc ttcacctaga tccttttaaa 7740 ttaaaaatga agttttaaat caatctaaag tatatatgag taaacttggt ctgacagtta 7800 ccaatgctta atcagtgagg cacctatctc agcgatctgt ctatttcgtt catccatagt 7860 tgcctgactc cccgtcgtgt agataactac gatacgggag ggcttaccat ctggccccag 7920 tgctgcaatg ataccgcgag acccacgctc accggctcca gatttatcag caataaacca 7980 gccagccgga agggccgagc gcagaagtgg tcctgcaact ttatccgcct ccatccagtc 8040 tattaattgt tgccgggaag ctagagtaag tagttcgcca gttaatagtt tgcgcaacgt 8100 tgttgccatt gctacaggca tcgtggtgtc acgctcgtcg tttggtatgg cttcattcag 8160 ctccggttcc caacgatcaa ggcgagttac atgatccccc atgttgtgca aaaaagcggt 8220 tagctccttc ggtcctccga tcgttgtcag aagtaagttg gccgcagtgt tatcactcat 8280 ggttatggca gcactgcata attctcttac tgtcatgcca tccgtaagat gcttttctgt 8340 gactggtgag tactcaacca agtcattctg agaatagtgt atgcggcgac cgagttgctc 8400 ttgcccggcg tcaatacggg ataataccgc gccacatagc agaactttaa aagtgctcat 8460 cattggaaaa cgttcttcgg ggcgaaaact ctcaaggatc ttaccgctgt tgagatccag 8520 ttcgatgtaa cccactcgtg cacccaactg atcttcagca tcttttactt tcaccagcgt 8580 ttctgggtga gcaaaaacag gaaggcaaaa tgccgcaaaa aagggaataa gggcgacacg 8640 gaaatgttga atactcatac tcttcctttt tcaatattat tgaagcattt atcagggtta 8700 ttgtctcatg agcggataca tatttgaatg tatttagaaa aataaacaaa taggggttcc 8760 gcgcacattt ccccgaaaag tgccacctga cg 8792 SEQ ID NO:212 gaggtccagc tggtgcagtc tggggctgag gtgaagaagc ctggggcctc agtgaaggtc 60 tcctgcaagg cttctgggta caccttcacc ggctactatg tgtactgggt gcgacaggcc 120 cctggacaag ggcttgagtg gatgggatgg atcagcgctt acaatggtaa cacaaactat 180 gcacagaagt tccagggcag agtcacgatt accgcggaca aatccacgag cacagcctac 240 atggagctga gcagcctgag atctgaagac acggctgtgt attactgtgc gagaagtaga 300 tccctggacg tctggggcca agggaccacg gtcaccgtct cgagcggtac gggcggttca 360 ggcggaaccg gcagcggcac tggcgggtcg acggatgttg tgatgactca gtctccagac 420 tccctggctg tgtctctggg cgagagggcc accatcaact gcaagtccag ccagagtgtt 480 ttatacagct ccaacaataa gaactactta gcttggtacc agcagaaacc aggacagcct 540 cctaagctgc tcatttactg ggcatctacc cgggaatccg gggtccctga ccgattcagt 600 ggcagcgggt ctgggacaga tttcactctc accatcagca gcctgcaggc tgaagatgtg 660 gcagtttatt actgtcagca atattatagt actcctctca ctttcggcgg agggaccaaa 720 gtggatatca aacgt 735 SEQ ID NO:213

EVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYVYWVR

QAPGQGLEWMGWISAYNGNTNYAQKFQGRVTITADKST

STAYMELSSLRSEDTAVYYCARSRSLDVWGQGTTVTVS

SGTGGSGGTGSGTGGSTDVVMTQSPDSLAVSLGERATI

NCKSSQSVLYSSNNKNYLAWYQQKPGQPPKLLIYWAST

RESGVPDRFSGSGSGTDFTLTISSLQAEDVAVYYCQQY

YSTPLTFGGGTKVDIKR SEQ ID NO:214 cagatgcagc tggtgcagtc tggggctgag gtgaagaagc ctgggtcctc ggtgaaggtc 60 tcctgcaagg cttctggagg caccttctcc agttatgcta tcacctgggt gcgacaggcc 120 cctggacaag ggcttgagtg gatgggaggg atcatcggta tgtttggttc aacaaactac 180 gcacagaact tccagggcag agtcacgatt accgcggacg aatccacgag cacagcctac 240 atggagctga gcagcctcag atctgaggac acggccgtgt attactgtgc gagaagtact 300 ggttattacc ctgcatacct ccaccactgg ggccagggca ccctggtcac cgtctcgagc 360 ggtacgggcg gttcaggcgg aaccggcagc ggcactggcg ggtcgacgca gtctgccctg 420 actcagcctc gctcagtgtc cgggtctcct ggacagtcag tcaccatctc ctgcactgga 480 accagcagtg atgttggtgg ttataactat gtctcctggt accaacagca cccaggcaaa 540 gcccccaaac tcatgattta tgatgtcagt aagcggccct caggggtccc tgatcgcttc 600 tctggctcca agtctggcaa cacggcctcc ctgaccatct ctgggctcca ggctgaggat 660 gaggctgatt attactgcag ctcatataca agcagcagca ctcatgtctt cggaactggg 720 accaaggtca ccgtcctagg t 741 SEQ ID NO:215

QMQLVQSGAEVKKPGSSVKVSCKASGGTFSSYAITWVR

QAPGQGLEWMGGIIGMFGSTNYAQNFQGRVTITADEST

STAYMELSSLRSEDTAVYYCARSTGYYPAYLHHWGQGT

LVTVSSGTGGSGGTGSGTGGSTQSALTQPRSVSGSPGQ

SVTISCTGTSSDVGGYNYVSWYQQHPGKAPKLMIYDVS

KRPSGVPDRFSGSKSGNTASLTISGLQAEDEADYYCSS

YTSSSTHVFGTGTKVTVLG SEQ ID NO:216 gaggtgcagc tggtggagac cggggctgag gtgaagaagc ctggggcctc agtgaaggtt 60 tcctgcaagg catctggata caccttcacc agctactata tgcactgggt gcgacaggcc 120 cctggacaag ggcttgagtg gatgggatgg atcaacccta acagtggtgg cacaaactat 180 gcacagaagt ttcagggcag ggtcaccatg accagggaca cgtccatcag cacagcctac 240 atggagctga gcaggctgag atctgacgac acggccgtgt attactgtgc gagagagggg 300 aaatggggac ctcaagcggc ttttgatatc tggggccaag ggacaatggt caccgtctcg 360 agcggtacgg gcggttcagg cggaaccggc agcggcactg gcgggtcgac ggaaattgtg 420 atgacgcagt ctccaggcac cctgtctttg tctccagggg aaagagccac cctctcctgc 480 agggccagtc agagtgttag cagcagctac ttagcctggt accagcagaa acctggccag 540 gctcccaggc tcctcatcta tgatgcatcc agcagggcca ctgacatccc agacaggttc 600 agtggcagtg ggtctgggac agacttcact ctcaccatca gcagactgga gcctgaagat 660 tttgcagtgt attactgtca gcagtatggt agctcacttt ggacgttcgg ccaagggacc 720 aaggtggaga tcaaacgt 738 SEQ ID NO:217

evqlvetgaevkkpgasvkvsckasgytftsyymhwvr QAPGQGLEWMGWINPNSGGTNYAQKFQGRVTMTRDTSI STAYMELSRLRSDDTAVYYCAREGKWGPQAAFDIWGQG TMVTVSSGTGGSGGTGSGTGGSTEIVMTQSPGTLSLSP GERATLSCRASQSVSSSYLAWYQQKPGQAPRLLIYDAS SRATDI PDRFSGSG SGT DFT LT I SRLE PEDFAVYYCQQ YGSSLWTFGQGTKVEIKR SEQ ID NO:218 gaggtgcagc tggtagagtc tgggggaggc ttggtacagc ctggggggtc cctgagactc 60 tcctgtgcag cctctggatt cacctttagc atctatgcca tgagctgggt ccgccaggca 120 ccagggaagg ggctggagtg ggtctcagct attagtagta gtggtgatag cacatactac 180 gcagactccg tgaagggccg gttcaccatc tccagagaca acgccaggaa cacgctgtat 240 ctgcaaatga acagtctgag agccgaggac acggctgtgt attactgtgc gagagcgtat 300 ggctacacgt tcgacccctg gggccaggga accctggtca ccgtctcgag cggtacgggc 360 ggttcaggcg gaaccggcag cggcactggc gggtcgacgg aaattgtgct gactcagtct 420 ccactctccc tgcccgtcac ccctggagag ccggcctcca tctcctgcag gtctagtcag 480 agcctcctgc atagtaatgg atacaactat ttggattggt acctgcagaa gccagggcag 540 tctccacagc tcctgatcta tttgggttct aatcgggcct ccggggtccc tgacaggttc 600 agtggcagtg gatcaggcac agattttaca ctgaaaatca gcagagtgga ggctgaggat 660 gttggggttt attactgcat gcaagctcta caaactcccc tcactttcgg cggagggacc 720 aaggtggaga tcaaacgt 738 SEQ ID NO:219

EVQLVESGGGLVQPGGSLRLSCAASGFTFSIYAMSWVR

QAPGKGLEWVSAISSSGDSTYYADSVKGRFTISRDNAR

NTLYLQMNSLRAEDTAVYYCARAYGYTFDPWGQGTLVT

VSSGTGGSGGTGSGTGGSTEIVLTQSPLSLPVTPGEPA

SISCRSSQSLLHSNGYNYLDWYLQKPGQSPQLLIYLGS

NRASGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCMQ

ALQTPLTFGGGTKVEIKR

SEQ ID NO:22Q gaggtgcagc tggtggagac cggggctgag gtgaagaagc ctgggtcctc ggtgaaggtc 60 tcctgcaagg cctctggagg caccttcagg acccatgcta tcagttgggt gcgacaggcc 120 cctggacaag ggcttgagtg gatgggaggg atcatcgcta tcttcggaac agcaaactac 180 gcacagaagt tccagggcag aatcacgatt accgcggacg aatccacgag tacagcctac 240 atggagctga gcagcctgag atctgaggac acggccgtgt atttctgtgc gagaggcagt 300 ggttatcata tatcgacacc ctttgacaac tggggccagg gaaccctggt caccgtctcg 360 agcggtacgg gcggttcagg cggaaccggc agcggcactg gcgggtcgac gtcctatgtg 420 ctgactcagc caccctcggt gtcagtggcc ccaggacaga cggccaggat tacctgtggg 480 ggaaacaaca ttggaagtaa aggtgtgcac tggtaccagc agaagcctgg ccaggcccct 540 gtgctggtcg tctatgatga tagcgaccgg ccctcaggga tccctgagcg attctctggc 600 tccaactctg ggaacacggc caccctgacc atcagcaggg tcgaagccgg ggatgaggcc 660 gactattact gtcaggtgtg ggatagtagt agtgatcatg tggtattcgg cggagggacc 720 aagctgaccg tcctaggt 738 SEQ ID NO:221

EVQLVETGAEVKKPGSSVKVSCKASGGTFRTHAISWVR QAPGQGLEWMGGIIAIFGTANYAQKFQGRITITADEST STAYMELSSLRSEDTAVYFCARGSGYHISTPFDNWGQG TLVTVSSGTGGSGGTGSGTGGSTSYVLTQPPSVSVAPG QTARITCGGNNIGSKGVHWYQQKPGQAPVLVVYDDSDR PSGI PERFSGSNSGNTAT LT I SRVEAGDEADYYCQVWD SSSDHVVFGGGTKLTVLG SEQ ID NO:222 gaggtgcagc tggtggagtc tggggctgag gtgaagaagc ctgggtcctc ggtgaaggtc 60 tcctgcaagg cttctggaca catcttcagc ggctatgcaa tcagttgggt gcgacaggcc 120 cctggacaag ggcttgagtg gatgggaggg atcatcccta tctttggtac aacaaactac 180 gcacagaagt tccagggcag agtcacgatt accgcggacc aatccacgag cacagcctac 240 atggacctga gcaacttgag atctgaggac acggccgtct attactgtgc gagagtgaaa 300 gatggatatt gtactcttac cagctgccct gtcggctggt acttcgatct ctggggccgt 360 ggcaccctgg tcactgtctc gagcggtacg ggcggttcag gcggaaccgg cagcggcact 420 ggcgggtcga cggaaattgt gatgacgcag tctccaggca ccctgtcttt gtctccaggg 480 gaaagagcca ccctctcgtg cagggccagt cagagtgtta gcagcagcta cttagcctgg 540 taccagcaga aacctggcca ggctcccagg ctcctcatct ttggtgcctc cagcagggcc 600 actggcatcc cagacaggtt cagtggcagt gggtctggga cagacttcac tctcaccatc 660 agcagactgg agcctgaaga ttttgcagtg tattactgtc agcagtatgg tagctcactc 720 actttcggcg gagggaccaa gctggagatc aaacgt 756 SEQ ID NO:223

EVQLVESGAEVKKPGSSVKVSCKASGHI FSGYAI SWVR qapgqglewmggiipifgttnyaqkfqgrvtitadqst

STAYMDLSNLRSEDTAVYYCARVKDGYCTLTSCPVGWY

FDLWGRGTLVTVSSGTGGSGGTGSGTGGSTEIVMTQSP

GTLSLSPGERATLSCRASQSVSSSYLAWYQQKPGQAPR

LLIFGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDF avyycqqygssltfgggtkleikr SEQ ID NO:224 gaggtccagc tggtacagtc tggggctgag gttaagaagc ctgggtcctc ggtgaaggtc 60 tcctgcaagg cttctggagg catcttcaga agcaattcta tcagttgggt gcgacaggcc 120 cctgggcaag ggcttgagtg gatgggaggg atcttcgctc ttttcggaac aacagactac 180 gcgcagaagt tccagggcag agtcacgatt accgcggacg aatcttcgac cacagtctac 240 ctggagctga gtagcctgac atctgaggac acggccgttt attactgtgc gagaggcagt 300 ggctacacca cacgcaacta ctttgactac tggggccagg gcaccctggt caccgtctcg 360 agcggtacgg gcggttcagg cggaaccggc agcggcactg gcgggtcgac ggaaattgtg 420 ctgactcagt ctccaggcac cctgtctttg tctccagggg aaagagccac actctcctgc 480 agggccagtc agagtgttag cagcaactac ttaggctggt accagcagaa acctggccag 540 gctcccaggc tcctgatcta tggtgcatcc agcagggcca gtggcatccc agacaggttc 600 agtggcggtg ggtctgggac agacttcact ctcaccatca gcagactgga gcctgaagat 660 tttgcagtgt attactgtca gcagtatggt agctcacccc tcactttcgg cggagggacc 720 aaggtggaga tcaaacgt 738 SEQ ID NO:225

EVQLVQS GAEVKKPGS SVKVSCKASGG I FRSNS I SWVR QAPGQGLEWMGGIFALFGTTDYAQKFQGRVTITADESS ttvylelssltsedtavyycargsgyttrnyfdywgqg tlvtvssgtggsggtgsgtggsteivltqspgtlslsp geratlscrasqsvssnylgwyqqkpgqaprlliygas srasgipdrfsgggsgtdftltisrlepedfavyycqq ygsspltfgggtkveikr SEQ ID NO:226 caggtgcagc tggtgcagtc tggggctgag gtgaagaagc ctgggtcctc ggtaaaggtc 60 tcctgcaagg cttctggagg ccccttccgc aattttgcta tcaactgggt gcgacaggcc 120 cctggacaag ggcttgagtg gatgggaggg atcatcgctg tctttgggac gacaaagtac 180 gcacataagt tccagggcag agtcaccatc accgcggacg actccacaaa tacagcttac 240 atggagctgg gcagcctgaa atctgaggac acggccgtgt attactgtgc gagaggtccc 300 cactactact cctcctacat ggacgtctgg ggcgaaggga ccacggtcac cgtctcgagc 360 ggtacgggcg gttcaggcgg aaccggcagc ggcactggcg ggtcgacgga catccagttg 420 acccagtctc catcctccct gtctgcatct gtaggagaca gagtcaccat cacttgccgg 480 gcgagtcagg gcattagcac ttatttagcc tggtatcagc agaaacccgg gaaagttcct 540 aaactcctga tctatgctgc atccactttg caatcagggg tcccatctcg gttcagtggc 600 agtggatctg ggacagattt cactctcacc atcagcagcc tgcagcctga agatgttgca 660 acttattact gtcaaaagta taacagtgcc ccttctttcg gccctgggac caaagtggat 720 atcaaacgt 729 SEQ ID NO:227

QVQLVQSGAEVKKPGSSVKVSCKASGGPFRNFAINWVR

QAPGQGLEWMGGIIAVFGTTKYAHKFQGRVTITADDST

NTAYMELGSLKSEDTAVYYCARGPHYYSSYMDVWGEGT

TVTVSSGTGGSGGTGSGTGGSTDIQLTQSPSSLSASVG

DRVTITCRASQGISTYLAWYQQKPGKVPKLLIYAASTL

QSGVPSRFSGSGSGTDFTLTISSLQPEDVATYYCQKYN

SAPSFGPGTKVDIKR SEQ ID NO:228 gaggtgcagc tggtggagac tggggctgag gtgaagaagc ctgggtcctc ggtgaaggtc 60 ccctgcaaat cttctggaag ccccttcagg agtaatgctg tcagctgggt gcgacaggcc 120 cccggacaag ggcttgagtg ggtgggagga atcctcggtg tctttggttc accaagctac 180 gcacagaagt tccagggcag agtcacgatt accgcggacg aatccaccaa cacagtccac 240 atggagctga gaggtttgag atctgaggac acggccgtgt attattgtgc gagaggtcct 300 acctactact actcctacat ggacgtctgg ggcaaaggga ccacggtcac cgtctcgagc 360 ggtacgggcg gttcaggcgg aaccggcagc ggcactggcg ggtcgacgtc ctatgtgctg 420 actcagccac cctcggagtc agtggcccca ggacagacgg ccaggattac ctgtggggga 480 aataacattg gaagaaatag tgtgcactgg tatcagcaga agccaggcca ggcccctgtg 540 ctggtcgtgt atgatgatag cgaccggccc tcagggatcc ctgagcgatt ttctggctcc 600 aagtctggga acacggccac cctgattatc agcagggtcg aagtcgggga tgaggccgac 660 tactactgtc aggtgtggca tagtagtagt gatcattatg tcttcggaac tgggaccaag 720 gtcaccgtcc taggt 735 SEQ ID NO:229

EVQLVETGAEVKKPGSSVKVPCKSSGSPFRSNAVSWVR

QAPGQGLEWVGGILGVFGSPSYAQKFQGRVTITADEST

NTVHMELRGLRSEDTAVYYCARGPTYYYSYMDVWGKGT

TVTVSSGTGGSGGTGSGTGGSTSYVLTQPPSESVAPGQ

TARITCGGNM3GRNSVHWYQQKPGQAPVLVVYDDSDRP

SGIPERFSGSKSGNTATLIISRVEVGDEADYYCQVWHS

SSDHYVFGTGTKVTVLG

SEQ ID NO:23Q cagatgcagc tggtacaatc tggagctgag gtgaagaagc ctgggtcctc ggtgaaggtc 60 tcctgcaagg cttctggagg caccttcagc agctatgcta tcagctgggt gcgacaggcc 120 cctggacaag ggcttgagtg gatgggaggg atcttcggta tgtttgggac agcaaactac 180 gcgcagaagt tccagggcag agtcacgatt accgcggacg aattcacgag cgcggcctac 240 atggagctga gcagcctggg atctgaggac acggccatgt attactgtgc gaggtctagt 300 ggttattacc cccaatactt ccaggactgg ggccagggca ccctggtcac cgtctcgagc 360 ggtacgggcg gttcaggcgg aaccggcagc ggcactggcg ggtcgacgga aattgtgatg 420 acacagtctc caggcaccct gtctttgtct ccagggcaaa gagccaccct ctcctgcagg 480 gccagtcaga gtgttagcag cagctactta gcctggtacc agcagaaacc tggccaggct 540 cccagactcc tcatgtatgg tgcatccagc agggccactg gcatcccaga caggttcagt 600 ggcagtgggt ctgggacaga cttcactctc accatcagca gactggagcc tgaagatttt 660 gcagtgtatt actgtcagca gtatggtagc tcatcgctca ctttcggcgg agggaccaag 720 ctggagatca aacgt 735 SEQ ID NO:231

Q M Q L v"q~s gaevkkpgssvkvsckasggtfssyaiswvr QAPGQGLEWMGGIFGMFGTANYAQKFQGRVTITADEFT saaymelsslgsedtamyycarssgyypqyfqdwgqgt

LVTVSSGTGGSGGTGSGTGGSTEIVMTQSPGTLSLSFG qratlscrasqsvsssylawyqqkpgqaprllmygass

RATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQY

GSSSLTFGGGTKLEIKR SEQ ID NO:232 gaggtgcagc tggtggagtc cggggctgag gtgaagaagc ctgggtcctc ggtgaaggtc 60 tcctgcaagg cttctggagg catcttcaac agttatgcta tcagctgggt gcgacaggcc 120 cctggacaag ggcttgagtg gatgggaggc atcatcgcta tctttcatac accaaagtac 180 gcacagaagt tccagggcag agtcacgatt accgcggacg aatccacgaa cacagcctac 240 atggaactga gaagcctgaa atctgaggac acggccctgt attactgtgc gagagggtcc 300 acttacgatt tttcgagtgg ccttgactac tggggccagg gaaccctggt caccgtctcg 360 agcggtacgg gcggttcagg cggaaccggc agcggcactg gcgggtcgac gcaggcaggg 420 ctgactcagc caccctcggt gtcagtggcc ccaggacaga cggccaggat tacctgtggg 480 ggaaacaaca ttggaagtaa aagtgtgcac tggtaccagc agaagccagg ccaggcccct 540 gtcctagtcg tctatgatga tagcgaccgg ccctcaggga tccctgagcg attctotggc 600 tccaactctg ggaacacggc caccctgacc atcagcaggg tcgaagccgg ggatgaggcc 660 gactattact gtcaggtgtg ggatagtagt agtgatcatg tggtattcgg cggagggacc 720 aagctgaccg tcctaggt 738 SEQ ID NO:233

EVQLVESGAEVKKPGSSVKVSCKASGGI FNSYAI SWVR QAPGQGLEWMGGIIAIFHTPKYAQKFQGRVTITADEST NTAYMELRSLKSEDTALYYCARGSTYDFSSGLDYWGQG TLVTVSSGTGGSGGTGSGTGGSTQAGLTQPPSVSVAPG QTARITCGGNNIGSKSVHWYQQKPGQAPVLVVYDDSDR P S G I PERFSGSNSGNTATLTI SRVEAGDEADYYCQVWD SSSDHVVFGGGTKLTVLG SEQ ID NO:234 caggtccagc tggtgcagtc tggggctgag gtgaagaagc ctgggtcctc ggtgaaggtc 60 tcctgcaagg cttctggagg cttcttcagc agctatgcta tcagctgggt gcgccaggcc 120 cctggacaag gacttgagtg gatggggggg gtcatcccta tctttcgtac agcaaactac 180 gcacagaact tccagggcag agtcaccatt accgcggacg aattcacatc gtatatggag 240 ctgagcagcc tgagatctga cgacacggcc gtgtattact gtgcgaggtt gaattaccat 300 gattcgggga cttattataa cgccccccgg ggctggttcg acccctgggg ccagggaacc 360 ctggtcaccg tctcgagcgg tacgggcggt tcaggcggaa ccggcagcgg cactggcggg 420 tcgacggaca tccagatgac ccagtctcca gactccctgg ctgtgtctct gggcgagaag 480 gccaccatca actgcaagtc cagccagagt attttaaaca gctccaacaa taagaactac 540 ttagcttggt accagcagaa accaggacag cctcctaagc tgctcattta ctgggcatct 600 acccgggaat ccggggtccc tgaccgattc agtggcagcg ggtctgggac agatttcact 660 ctcaccatca gcagcctgca ggctgaagat gtggcagttt attactgtca gcaatattat 720 agtagtccgc cgacgttcgg ccaagggacc aaggtggaaa tcaaacgt 768 SEQ ID NO:235

QVQLVQSGAEVKKPGSSVKVSCKASGGFFSSYAISWVR

QAPGQGLEWMGGVIPIFRTANYAQNFQGRVTITADEFT

SYMELSSLRSDDTAVYYCARLNYHDSGTYYNAPRGWFD

PWGQGTLVTVSSGTGGSGGTGSGTGGSTDIQMTQSPDS

LAVSLGEKATINCKSSQSILNSSNNKNYLAWYQQKPGQ ppklliywastresgvpdrfsgsgsgtdftltisslqa

EDVAVYYCQQYYSSPPTFGQGTKVEIKR SEQ ID NO:236 caggtccagc tggtgcagtc tggagctgag gtgaagaagc ctgggtcctc ggtgaaggtc 60 tcctgcaagg cttctggagt caccttcagt tactatgcta tgagctgggt gcgacaggcc 120 cctggacaag ggcttgagtg gatgggagga atcagcccta tgtttgggac aacaacctac 180 gcacagaagt tccagggcag agtcacgatt actgcggacg actccacgag tacagcctac 240 atggaggtga ggagcctgag atctgaggac acggccgtgt attactgtgc gagatcttcg 300 aattactatg atagtgtata tgactactgg ggccagggaa ccctggtcac cgtctcgagc 360 ggtacgggcg gttcaggcgg aaccggcagc ggcactggcg ggtcgacgca gtctgtcgtg 420 acgcagccgc cctcggagtc agtggcccca ggacagacgg ccaggattac ctgtggggga 480 cataacattg gaagtaatag tgtgcactgg taccagcaga agccaggcca ggcccctgtg 540 ctggtcgtgt atgataatag cgaccggccc tcagggatcc ctgagcgatt ctctggctcc 600 aactctggga acacggccac cctgaccatc agcagggtcg aagccgggga tgaggccgac 660 tattactgtc aggtgtgggg tagtagtagt gaccattatg tcttcggaac tgggaccaag 720 gtcaccgtcc taggt 735 SEQ ID NO:237

QVQLVQSGAEVKKPGSSVKVSCKASGVTFSYYAMSWVR QAPGQGLEWMGG I S PMFGTTTYAQKFQGRVT I TADDST STAYMEVRSLRSEDTAVYYCARSSNYYDSVYDYWGQGT LVTVSSGTGGSGGTGSGTGGSTQSVVTQPPSESVAPGQ TARITCGGHNIGSNSVHWYQQKPGQAPVLVVYDNSDRP SGIPERFSGSNSGNTATLTISRVEAGDEADYYCQVWGS SSDHYVFGTGTKVTVLG SEQ ID NO:316 gaggtccagc tggtgcagtc tggggctgag gtgaagaagc ctggggcctc agtgaaggtc 60 tcctgcaagg cttctgggta caccttcacc ggctactatg tgtactgggt gcgacaggcc 120 cctggacaag ggcttgagtg gatgggatgg atcagcgctt acaatggtaa cacaaactat 180 gcacagaagt tccagggcag agtcacgatt accgcggaca aatccacgag cacagcctac 240 atggagctga gcagcctgag atctgaagac acggctgtgt attactgtgc gagaagtaga 300 tccctggacg tctggggcca agggaccacg gtcaccgtct cgagtgctag caccaagggc 360 cccagcgtgt tccccctggc ccccagcagc aagagcacca gcggcggcac agccgccctg 420 ggctgcctgg tgaaggacta cttccccgag cccgtgaccg tgagctggaa cagcggcgcc 480 ttgaccagcg gcgtgcacac cttccccgcc gtgctgcaga gcagcggcct gtacagcctg 540 agcagcgtgg tgaccgtgcc cagcagcagc ctgggcaccc agacctacat ctgcaacgtg 600 aaccacaagc ccagcaacac caaggtggac aaacgcgtgg agcccaagag ctgcgacaag 660 acccacacct gccccccctg ccctgccccc gagctgctgg gcggaccctc cgtgttcctg 720 ttccccccca agcccaagga caccctcatg atcagccgga cccccgaggt gacctgcgtg 780 gtggtggacg tgagccacga ggaccccgag gtgaagttca actggtacgt ggacggcgtg 840 gaggtgcaca acgccaagac caagccccgg gaggagcagt acaacagcac ctaccgggtg 900 gtgagcgtgc tcaccgtgct gcaccaggac tggctgaacg gcaaggagta caagtgcaag 960 gtgagcaaca aggccctgcc tgcccccatc gagaagacca tcagcaaggc caagggccag 1020 ccccgggagc cccaggtgta caccctgccc cccagccggg aggagatgac caagaaccag 1080 gtgtccctca cctgtctggt gaagggcttc taccccagcg acatcgccgt ggagtgggag 1140 agcaacggcc agcccgagaa caactacaag accacccccc ctgtgctgga cagcgacggc 1200 agcttcttcc tgtacagcaa gctcaccgtg gacaagagcc ggtggcagca gggcaacgtg 1260 ttcagctgca gcgtgatgca cgaggccctg cacaaccact acacccagaa gagcctgagc 1320 ctgagccccg gcaag 1335 SEQ ID NO:317

EVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYVYWVR

QAPGQGLEWMGWISAYNGNTNYAQKFQGRVTITADKST

STAYMELSSLRSEDTAVYYCARSRSLDVWGQGTTVTVS

SASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPV

TVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSS

LGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCP

APELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSH

EDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVL

TVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPR

EPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWE

SNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQG

NVFSCSVMHEALHNHYTQKSLSLSPGK SEQ ID NO:318 gatgttgtga tgactcagtc tccagactcc ctggctgtgt ctctgggcga gagggccacc 60 atcaactgca agtccagcca gagtgtttta tacagctcca acaataagaa ctacttagct 120 tggtaccagc agaaaccagg acagcctcct aagctgctca tttactgggc atctacccgg 180 gaatccgggg tccctgaccg attcagtggc agcgggtctg ggacagattt cactctcacc 240 atcagcagcc tgcaggctga agatgtggca gtttattact gtcagcaata ttatagtact 300 cctctcactt tcggcggagg gaccaaagtg gatatcaaac gtgcggccgc acccagcgtg 360 ttcatcttcc ccccctccga cgagcagctg aagagcggca ccgccagcgt ggtgtgcctg 420 ctgaacaact tctacccccg ggaggccaag gtgcagtgga aggtggacaa cgccctgcag 480 agcggcaaca gccaggagag cgtgaccgag caggacagca aggactccac ctacagcctg 540 agcagcaccc tcaccctgag caaggccgac tacgagaagc acaaggtgta cgcctgcgag 600 gtgacccacc agggcctgag cagccccgtg accaagagct tcaaccgggg cgagtgt 657 SEQ ID NO:319

DVVMTQSPDSLAVSLGERATINCKSSQSVLYSSNNKNY LAWYQQKPGQPPKLLIYWASTRESGVPDRFSGSGSGTD FTLT I SSLQAEDVAVYYCQQYY ST PLTFGGGTKVDI KR AAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQ WKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKAD YEKHKVYACEVTHQGLS S PVTKSFNRGEC

SEQ ID NO:32Q cagatgcagc tggtgcagtc tggggctgag gtgaagaagc ctgggtcctc ggtgaaggtc 60 tcctgcaagg cttctggagg caccttctcc agttatgcta tcacctgggt gcgacaggcc 120 cctggacaag ggcttgagtg gatgggaggg atcatcggta tgtttggttc aacaaactac 180 gcacagaact tccagggcag agtcacgatt accgcggacg aatccacgag cacagcctac 240 atggagctga gcagcctcag atctgaggac acggccgtgt attactgtgc gagaagtact 300 ggttattacc ctgcatacct ccaccactgg ggccagggca ccctggtcac cgtctcgagt 360 gctagcacca agggccccag cgtgttcccc ctggccccca gcagcaagag caccagcggc 420 ggcacagccg ccctgggctg cctggtgaag gactacttcc ccgagcccgt gaccgtgagc 480 tggaacagcg gcgccttgac cagcggcgtg cacaccttcc ccgccgtgct gcagagcagc 540 ggcctgtaca gcctgagcag cgtggtgacc gtgcccagca gcagcctggg cacccagacc 600 tacatctgca acgtgaacca caagcccagc aacaccaagg tggacaaacg cgtggagccc 660 aagagctgcg acaagaccca cacctgcccc ccctgccctg cccccgagct gctgggcgga 720 ccctccgtgt tcctgttccc ccccaagccc aaggacaccc tcatgatcag ccggaccccc 780 gaggtgacct gcgtggtggt ggacgtgagc cacgaggacc ccgaggtgaa gttcaactgg 840 tacgtggacg gcgtggaggt gcacaacgcc aagaccaagc cccgggagga gcagtacaac 900 agcacctacc gggtggtgag cgtgctcacc gtgctgcacc aggactggct gaacggcaag 960 gagtacaagt gcaaggtgag caacaaggcc ctgcctgccc ccatcgagaa gaccatcagc 1020 aaggccaagg gccagccccg ggagccccag gtgtacaccc tgccccccag ccgggaggag 1080 atgaccaaga accaggtgtc cctcacctgt ctggtgaagg gcttctaccc cagcgacatc 1140 gccgtggagt gggagagcaa cggccagccc gagaacaact acaagaccac cccccctgtg 1200 ctggacagcg acggcagctt cttcctgtac agcaagctca ccgtggacaa gagccggtgg 1260 cagcagggca acgtgttcag ctgcagcgtg atgcacgagg ccctgcacaa ccactacacc 1320 cagaagagcc tgagcctgag ccccggcaag 1350 SEQ ID NO:321

QMQLVQSGAEVKKPGSSVKVSCKASGGTFSSYAITWVR

QAPGQGLEWMGGIIGMFGSTNYAQNFQGRVTITADEST

STAYMELSSLRSEDTAVYYCARSTGYYPAYLHHWGQGT

LVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDY

FPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVT

VPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHT

CPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVV

VDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYR

VVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKA

KGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDI

AVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKS

RWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK SEQ ID NO:322 cagtctgccc tgactcagcc tcgctcagtg tccgggtctc ctggacagtc agtcaccatc 60 tcctgcactg gaaccagcag tgatgttggt ggttataact atgtctcctg gtaccaacag 120 cacccaggca aagcccccaa actcatgatt tatgatgtca gtaagcggcc ctcaggggtc 180 cctgatcgct tctctggctc caagtctggc aacacggcct ccctgaccat ctctgggctc 240 caggctgagg atgaggctga ttattactgc agctcatata caagcagcag cactcatgtc 300 ttcggaactg ggaccaaggt caccgtccta ggtgcggccg caggccagcc caaggccgct 360 cccagcgtga ccctgttccc cccctcctcc gaggagctgc aggccaacaa ggccaccctg 420 gtgtgcctca tcagcgactt ctaccctggc gccgtgaccg tggcctggaa ggccgacagc 480 agccccgtga aggccggcgt ggagaccacc acccccagca agcagagcaa caacaagtac 540 gccgccagca gctacctgag cctcaccccc gagcagtgga agagccaccg gagctacagc 600 tgccaggtga cccacgaggg cagcaccgtg gagaagaccg tggcccccac cgagtgcagc 660 SEQ ID NO:323

QSALTQPRSVSGSPGQSVTISCTGTSSDVGGYNYVSWY QQHPGKAPKLMIYDVSKRPSGVPDRFSGSKSGNTASLT ISGLQAEDEADYYCSSYTSSSTHVFGTGTKVTVLGAAA GQPKAAPSVTLFPPSSEELQANKATLVCL I S DFYPGAV TVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTP EQWKSHRSYSCQVTHEGSTVEKTVAPTECS SEQ ID NO:324 gaggtgcagc tggtggagac cggggctgag gtgaagaagc ctggggcctc agtgaaggtt 60 tcctgcaagg catctggata caccttcacc agctactata tgcactgggt gcgacaggcc 120 cctggacaag ggcttgagtg gatgggatgg atcaacccta acagtggtgg cacaaactat 180 gcacagaagt ttcagggcag ggtcaccatg accagggaca cgtccatcag cacagcctac 240 atggagctga gcaggctgag atctgacgac acggccgtgt attactgtgc gagagagggg 300 aaatggggac ctcaagcggc ttttgatatc tggggccaag ggacaatggt caccgtctcg 360 agtgctagca ccaagggccc cagcgtgttc cccctggccc ccagcagcaa gagcaccagc 420 ggcggcacag ccgccctggg ctgcctggtg aaggactact tccccgagcc cgtgaccgtg 480 agctggaaca gcggcgcctt gaccagcggc gtgcacacct tccccgccgt gctgcagagc 540 agcggcctgt acagcctgag cagcgtggtg accgtgccca gcagcagcct gggcacccag 600 acctacatct gcaacgtgaa ccacaagccc agcaacacca aggtggacaa acgcgtggag 660 cccaagagct gcgacaagac ccacacctgc cccccctgcc ctgcccccga gctgctgggc 720 ggaccctccg tgttcctgtt cccccccaag cccaaggaca ccctcatgat cagccggacc 780 cccgaggtga cctgcgtggt ggtggacgtg agccacgagg accccgaggt gaagttcaac 840 tggtacgtgg acggcgtgga ggtgcacaac gccaagacca agccccggga ggagcagtac 900 aacagcacct accgggtggt gagcgtgctc accgtgctgc accaggactg gctgaacggc 960 aaggagtaca agtgcaaggt gagcaacaag gccctgcctg cccccatcga gaagaccatc 1020 agcaaggcca agggccagcc ccgggagccc caggtgtaca ccctgccccc cagccgggag 1080 gagatgacca agaaccaggt gtccctcacc tgtctggtga agggcttcta ccccagcgac 1140 atcgccgtgg agtgggagag caacggccag cccgagaaca actacaagac caccccccct 1200 gtgctggaca gcgacggcag cttcttcctg tacagcaagc tcaccgtgga caagagccgg 1260 tggcagcagg gcaacgtgtt cagctgcagc gtgatgcacg aggccctgca caaccactac 1320 acccagaaga gcctgagcct gagccccggc aag 1353 SEQ ID NO:325

EVQLVETGAEVKKPGASVKVSCKASGYTFTSYYMHWVR

QAPGQGLEWMGWINPNSGGTNYAQKFQGRVTMTRDTSI

STAYMELSRLRSDDTAVYYCAREGKWGPQAAFDIWGQG

TMVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKD

YFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVV

TVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTH

TCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCV

VVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTY

RVVSVLTVLHQDWLNGKEYKCKVSNKALPAFIEKTISK

AKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSD

IAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDK

SRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK SEQ ID NO:326 gaaattgtga tgacgcagtc tccaggcacc ctgtctttgt ctccagggga aagagccacc 60 ctctcctgca gggccagtca gagtgttagc agcagctact tagcctggta ccagcagaaa 120 cctggccagg ctcccaggct cctcatctat gatgcatcca gcagggccac tgacatccca 180 gacaggttca gtggcagtgg gtctgggaca gacttcactc tcaccatcag cagactggag 240 cctgaagatt ttgcagtgta ttactgtcag cagtatggta gctcactttg gacgttcggc 300 caagggacca aggtggagat caaacgtgcg gccgcaccca gcgtgttcat cttccccccc 360 tccgacgagc agctgaagag cggcaccgcc agcgtggtgt gcctgctgaa caacttctac 420 ccccgggagg ccaaggtgca gtggaaggtg gacaacgccc tgcagagcgg caacagccag 480 gagagcgtga ccgagcagga cagcaaggac tccacctaca gcctgagcag caccctcacc 540 ctgagcaagg ccgactacga gaagcacaag gtgtacgcct gcgaggtgac ccaccagggc 600 ctgagcagcc ccgtgaccaa gagcttcaac cggggcgagt gt 642 SEQ ID NO:327

EIVMTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQ QKPGQAPRLLIYDASSRATDI PDRFSGSGSGTDFTLT I SRLEPEDFAVYYCQQYGSSLWTFGQGTKVEIKRAAAPS VFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDN ALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHK VYACEVTHQGLSSPVTKSFNRGEC SEQ ID NO:328 gaggtgcagc tggtagagtc tgggggaggc ttggtacagc ctggggggtc cctgagactc 60 tcctgtgcag cctctggatt cacctttagc atctatgcca tgagctgggt ccgccaggca 120 ccagggaagg ggctggagtg ggtctcagct attagtagta gtggtgatag cacatactac 180 gcagactccg tgaagggccg gttcaccatc tccagagaca acgccaggaa cacgctgtat 240 ctgcaaatga acagtctgag agccgaggac acggctgtgt attactgtgc gagagcgtat 300 ggctacacgt tcgacccctg gggccaggga accctggtca ccgtctcgag tgctagcacc 360 aagggcccca gcgtgttccc cctggccccc agcagcaaga gcaccagcgg cggcacagcc 420 gccctgggct gcctggtgaa ggactacttc cccgagcccg tgaccgtgag ctggaacagc 480 ggcgccttga ccagcggcgt gcacaccttc cccgccgtgc tgcagagcag cggcctgtac 540 agcctgagca gcgtggtgac cgtgcccagc agcagcctgg gcacccagac ctacatctgc 600 aacgtgaacc acaagcccag caacaccaag gtggacaaac gcgtggagcc caagagctgc 660 gacaagaccc acacctgccc cccctgccct gcccccgagc tgctgggcgg accctccgtg 720 ttcctgttcc cccccaagcc caaggacacc ctcatgatca gccggacccc cgaggtgacc 780 tgcgtggtgg tggacgtgag ccacgaggac cccgaggtga agttcaactg gtacgtggac 840 ggcgtggagg tgcacaacgc caagaccaag ccccgggagg agcagtacaa cagcacctac 900 cgggtggtga gcgtgctcac cgtgctgcac caggactggc tgaacggcaa ggagtacaag 960 tgcaaggtga gcaacaaggc cctgcctgcc cccatcgaga agaccatcag caaggccaag 1020 ggccagcccc gggagcccca ggtgtacacc ctgcccccca gccgggagga gatgaccaag 1080 aaccaggtgt ccctcacctg tctggtgaag ggcttctacc ccagcgacat cgccgtggag 1140 tgggagagca acggccagcc cgagaacaac tacaagacca ccccccctgt gctggacagc 1200 gacggcagct tcttcctgta cagcaagctc accgtggaca agagccggtg gcagcagggc 1260 aacgtgttca gctgcagcgt gatgcacgag gccctgcaca accactacac ccagaagagc 1320 ctgagcctga gccccggcaa g 1341 SEQ ID NO:329

EVQLVESGGGLVQPGGSLRLSCAASGFTFSIYAMSWVR

QAPGKGLEWVSAISSSGDSTYYADSVKGRFTISRDNAR

NTLYLQMNSLRAEDTAVYYCARAYGYTFDPWGQGTLVT

VSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPE

PVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPS

SSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPP

CPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDV

SHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVS

VLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQ

PREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVE

WESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQ

QGNVFSCSVMHEALHNHYTQKSLSLSPGK

SEQ ID NO:33Q gaaattgtgc tgactcagtc tccactctcc ctgcccgtca cccctggaga gccggcctcc 60 atctcctgca ggtctagtca gagcctcctg catagtaatg gatacaacta tttggattgg 120 tacctgcaga agccagggca gtctccacag ctcctgatct atttgggttc taatcgggcc 180 tccggggtcc ctgacaggtt cagtggcagt ggatcaggca cagattttac actgaaaatc 240 agcagagtgg aggctgagga tgttggggtt tattactgca tgcaagctct acaaactccc 300 ctcactttcg gcggagggac caaggtggag atcaaacgtg cggccgcacc cagcgtgttc 360 atcttccccc cctccgacga gcagctgaag agcggcaccg ccagcgtggt gtgcctgctg 420 aacaacttct acccccggga ggccaaggtg cagtggaagg tggacaacgc cctgcagagc 480 ggcaacagcc aggagagcgt gaccgagcag gacagcaagg actccaccta cagcctgagc 540 agcaccctca ccctgagcaa ggccgactac gagaagcaca aggtgtacgc ctgcgaggtg 600 acccaccagg gcctgagcag ccccgtgacc aagagcttca accggggcga gtgt 654 SEQ ID NO:331

EIVLTQSPLSLPVTPGEPASISCRSSQSLLHSNGYNYL DWYLQKPGQSPQLLIYLGSNRASGVPDRFSGSGSGTDF T LKI SRVEAEDVGVYYCMQALQT PLTFGGGTKVE I KRA AAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQW KVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADY EKHKVYACEVTHQGLSSPVTKSFNRGEC SEQ ID NO:332 gaggtgcagc tggtggagac cggggctgag gtgaagaagc ctgggtcctc ggtgaaggtc 60 tcctgcaagg cctctggagg caccttcagg acccatgcta tcagttgggt gcgacaggcc 120 cctggacaag ggcttgagtg gatgggaggg atcatcgcta tcttcggaac agcaaactac 180 gcacagaagt tccagggcag aatcacgatt accgcggacg aatccacgag tacagcctac 240 atggagctga gcagcctgag atctgaggac acggccgtgt atttctgtgc gagaggcagt 300 ggttatcata tatcgacacc ctttgacaac tggggccagg gaaccctggt caccgtctcg 360 agtgctagca ccaagggccc cagcgtgttc cccctggccc ccagcagcaa gagcaccagc 420 ggcggcacag ccgccctggg ctgcctggtg aaggactact tccccgagcc cgtgaccgtg 480 agctggaaca gcggcgcctt gaccagcggc gtgcacacct tccccgccgt gctgcagagc 540 agcggcctgt acagcctgag cagcgtggtg accgtgccca gcagcagcct gggcacccag 600 acctacatct gcaacgtgaa ccacaagccc agcaacacca aggtggacaa acgcgtggag 660 cccaagagct gcgacaagac ccacacctgc cccccctgcc ctgcccccga gctgctgggc 720 ggaccctccg tgttcctgtt cccccccaag cccaaggaca ccctcatgat cagccggacc 780 cccgaggtga cctgcgtggt ggtggacgtg agccacgagg accccgaggt gaagttcaac 840 tggtacgtgg acggcgtgga ggtgcacaac gccaagacca agccccggga ggagcagtac 900 aacagcacct accgggtggt gagcgtgctc accgtgctgc accaggactg gctgaacggc 960 aaggagtaca agtgcaaggt gagcaacaag gccctgcctg cccccatcga gaagaccatc 1020 agcaaggcca agggccagcc ccgggagccc caggtgtaca ccctgccccc cagccgggag 1080 gagatgacca agaaccaggt gtccctcacc tgtctggtga agggcttcta ccccagcgac 1140 atcgccgtgg agtgggagag caacggccag cccgagaaca actacaagac caccccccct 1200 gtgctggaca gcgacggcag cttcttcctg tacagcaagc tcaccgtgga caagagccgg 1260 tggcagcagg gcaacgtgtt cagctgcagc gtgatgcacg aggccctgca caaccactac 1320 acccagaaga gcctgagcct gagccccggc aag 1353 SEQ ID NO:333

EVQLVETGAEVKKPGSSVKVSCKASGGTFRTHAISWVR QAPGQGLEWMGG I IAI FGTANYAQKFQGRI Ί I TADE $T STAYMELSSLRSEDTAVYFCARGSGYHISTPFDNWGQG TLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKD YFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVV TVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTH TCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCV VVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTY RVVSVLTVLHQDWLNGKEYKCKV SNKALPAP I ΕΚΤ I SK AKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSD IAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDK SRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK SEQ ID NO:334 tcctatgtgc tgactcagcc accctcggtg tcagtggccc caggacagac ggccaggatt 60 acctgtgggg gaaacaacat tggaagtaaa ggtgtgcact ggtaccagca gaagcctggc 120 caggcccctg tgctggtcgt ctatgatgat agcgaccggc cctcagggat ccctgagcga 180 ttctctggct ccaactctgg gaacacggcc accctgacca tcagcagggt cgaagccggg 240 gatgaggccg actattactg tcaggtgtgg gatagtagta gtgatcatgt ggtattcggc 300 ggagggacca agctgaccgt cctaggtgcg gccgcaggcc agcccaaggc cgctcccagc 360 gtgaccctgt tccccccctc ctccgaggag ctgcaggcca acaaggccac cctggtgtgc 420 ctcatcagcg acttctaccc tggcgccgtg accgtggcct ggaaggccga cagcagcccc 480 gtgaaggccg gcgtggagac caccaccccc agcaagcaga gcaacaacaa gtacgccgcc 540 agcagctacc tgagcctcac ccccgagcag tggaagagcc accggagcta cagctgccag 600 gtgacccacg agggcagcac cgtggagaag accgtggccc ccaccgagtg cage 654 SEQ ID NO:335

SYVLTQPPSVSVAPGQTARITCGGNNIGSKGVHWYQQK

PGQAPVLVVYDDSDRPSGIPERFSGSNSGNTATLTISR

VEAGDEADYYCQVWDSSSDHVVFGGGTKLTVLGAAAGQ

PKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTV

AWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQ

WKSHRSYSCQVTHEGSTVEKTVAPTECS SEQ ID NO:336 gaggtgcagc tggtggagtc tggggctgag gtgaagaagc ctgggtcctc ggtgaaggtc 60 tcctgcaagg ettetggaea catcttcagc ggctatgcaa tcagttgggt gcgacaggcc 120 cctggacaag ggcttgagtg gatgggaggg atcatcccta tctttggtac aacaaactac 180 gcacagaagt tccagggcag agtcacgatt accgcggacc aatccacgag cacagcctac 240 atggacctga gcaacttgag atctgaggac acggccgtct attactgtgc gagagtgaaa 300 gatggatatt gtactcttac cagctgccct gtcggctggt aettegatet ctggggccgt 360 ggcaccctgg tcactgtctc gagtgetage accaagggcc ccagcgtgtt ccccctggcc 420 cccagcagca agagcaccag cggcggcaca gccgccctgg gctgcctggt gaaggactac 480 ttccccgagc ccgtgaccgt gagetggaae agcggcgcct tgaccagcgg cgtgcacacc 540 ttccccgccg tgetgeagag cagcggcctg tacagcctga geagegtggt gaccgtgccc 600 agcagcagcc tgggcaccca gacctacatc tgcaacgtga accacaagcc cagcaacacc 660 aaggtggaca aacgcgtgga gcccaagagc tgcgacaaga cccacacctg ccccccctgc 720 cctgcccccg agctgctggg cggaccctcc gtgttcctgt tcccccccaa gcccaaggac 780 accctcatga tcagccggac ccccgaggtg acctgcgtgg tggtggacgt gagccacgag 840 gaccccgagg tgaagttcaa ctggtacgtg gaeggegtgg aggtgcacaa cgccaagacc 900 aagccccggg aggageagta caacagcacc taccgggtgg tgagegtget caccgtgctg 960 caccaggact ggetgaaegg caaggagtac aagtgcaagg tgagcaacaa ggccctgcct 1020 gcccccatcg agaagaccat cagcaaggcc aagggccagc cccgggagcc ccaggtgtac 1080 accctgcccc ccagccggga ggagatgacc aagaaccagg tgtccctcac ctgtctggtg 1140 aagggcttct accccagcga catcgccgtg gagtgggaga gcaacggcca gcccgagaac 1200 aactacaaga ccaccccccc tgtgctggac agcgacggca gcttcttcct gtacagcaag 1260 ctcaccgtgg acaagagccg gtggcagcag ggcaacgtgt tcagctgcag cgtgatgcac 1320 gaggccctgc acaaccacta cacccagaag agcctgagcc tgagccccgg caag 1374 SEQ ID NO:337

EVQLVESGAEVKKPGSSVKVSCKASGHI FSGYAI SWVR QAPGQGLEWMGGIIPIFGTTNYAQKFQGRVTITADQST STAYMDLSNLRSEDTAVYYCARVKDGYCTLTSCPVGWY FDLWGRGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAA LGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGL YSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEP KSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISR TPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPRE EQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAP IEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLV KGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLY SKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSP G K SEQ ID NO:338 gaaattgtga tgacgcagtc tccaggcacc ctgtctttgt ctccagggga aagagccacc 60 ctctcgtgca gggccagtca gagtgttagc agcagctact tagcctggta ccagcagaaa 120 cctggccagg ctcccaggct cctcatcttt ggtgcctcca gcagggccac tggcatccca 180 gacaggttca gtggcagtgg gtctgggaca gacttcactc tcaccatcag cagactggag 240 cctgaagatt ttgcagtgta ttactgtcag cagtatggta gctcactcac tttcggcgga 300 gggaccaagc tggagatcaa acgtgcggcc gcacccagcg tgttcatctt ccccccctcc 360 gacgagcagc tgaagagcgg caccgccagc gtggtgtgcc tgctgaacaa cttctacccc 420 cgggaggcca aggtgcagtg gaaggtggac aacgccctgc agagcggcaa cagccaggag 480 agcgtgaccg agcaggacag caaggactcc acctacagcc tgagcagcac cctcaccctg 540 agcaaggccg actacgagaa gcacaaggtg tacgcctgcg aggtgaccca ccagggcctg 600 agcagccccg tgaccaagag cttcaaccgg ggcgagtgt 639 SEQ ID NO:339

EIVMTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQ QKPGQAPRLL I FGASSRATGI PDRFSGSGSGTDFTLT I SRLEPEDFAVYYCQQYGSSLTFGGGTKLEIKRAAAPSV FIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNA LQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKV YACEVTHQGLSSPVTKSFNRGEC

SEQ ID NO:34Q gaggtccagc tggtacagtc tggggctgag gttaagaagc ctgggtcctc ggtgaaggtc 60 tcctgcaagg cttctggagg catcttcaga agcaattcta tcagttgggt gcgacaggcc 120 cctgggcaag ggcttgagtg gatgggaggg atcttcgctc ttttcggaac aacagactac 180 gcgcagaagt tccagggcag agtcacgatt accgcggacg aatcttcgac cacagtctac 240 ctggagctga gtagcctgac atctgaggac acggccgttt attactgtgc gagaggcagt 300 ggctacacca cacgcaacta ctttgactac tggggccagg gcaccctggt caccgtctcg 360 agtgctagca ccaagggccc cagcgtgttc cccctggccc ccagcagcaa gagcaccagc 420 ggcggcacag ccgccctggg ctgcctggtg aaggactact tccccgagcc cgtgaccgtg 480 agctggaaca gcggcgcctt gaccagcggc gtgcacacct tccccgccgt gctgcagagc 540 agcggcctgt acagcctgag cagcgtggtg accgtgccca gcagcagcct gggcacccag 600 acctacatct gcaacgtgaa ccacaagccc agcaacacca aggtggacaa acgcgtggag 660 cccaagagct gcgacaagac ccacacctgc cccccctgcc ctgcccccga gctgctgggc 720 ggaccctccg tgttcctgtt cccccccaag cccaaggaca ccctcatgat cagccggacc 780 cccgaggtga cctgcgtggt ggtggacgtg agccacgagg accccgaggt gaagttcaac 840 tggtacgtgg acggcgtgga ggtgcacaac gccaagacca agccccggga ggagcagtac 900 aacagcacct accgggtggt gagcgtgctc accgtgctgc accaggactg gctgaacggc 960 aaggagtaca agtgcaaggt gagcaacaag gccctgcctg cccccatcga gaagaccatc 1020 agcaaggcca agggccagcc ccgggagccc caggtgtaca ccctgccccc cagccgggag 1080 gagatgacca agaaccaggt gtccctcacc tgtctggtga agggcttcta ccccagcgac 1140 atcgccgtgg agtgggagag caacggccag cccgagaaca actacaagac caccccccct 1200 gtgctggaca gcgacggcag cttcttcctg tacagcaagc tcaccgtgga caagagccgg 1260 tggcagcagg gcaacgtgtt cagctgcagc gtgatgcacg aggccctgca caaccactac 1320 acccagaaga gcctgagcct gagccccggc aag 1353 SEQ ID NO:341

EVQLVQSGAEVKKPGS SVKVSCKASGG I FRSNS I SWVR QAPGQGLEWMGGI FALFGTTDYAQKFQGRVT I TADE S S TTVYLELSSLTSEDTAVYYCARGSGYTTRNYFDYWGQG TLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKD YFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVV TVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTH TCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCV VVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTY RVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISK AKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSD IAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDK SRWQQGNVFSC SVMHEALHNHYTQKSL SL S PGK SEQ ID NO:342 gaaattgtgc tgactcagtc tccaggcacc ctgtctttgt ctccagggga aagagccaca 60 ctctcctgca gggccagtca gagtgttagc agcaactact taggctggta ccagcagaaa 120 cctggccagg ctcccaggct cctgatctat ggtgcatcca gcagggccag tggcatccca 180 gacaggttca gtggcggtgg gtctgggaca gacttcactc tcaccatcag cagactggag 240 cctgaagatt ttgcagtgta ttactgtcag cagtatggta gctcacccct cactttcggc 300 ggagggacca aggtggagat caaacgtgcg gccgcaggcc agcccaaggc cgctcccagc 360 gtgaccctgt tccccccctc ctccgaggag ctgcaggcca acaaggccac cctggtgtgc 420 ctcatcagcg acttctaccc tggcgccgtg accgtggcct ggaaggccga cagcagcccc 480 gtgaaggccg gcgtggagac caccaccccc agcaagcaga gcaacaacaa gtacgccgcc 540 agcagctacc tgagcctcac ccccgagcag tggaagagcc accggagcta cagctgccag 600 gtgacccacg agggcagcac cgtggagaag accgtggccc ccaccgagtg cage 654 SEQ ID NO:343 eivltqspgtlslspgeratlscrasqsvssnylgwyq

QKPGQAPRLLIYGASSRASGIPDRFSGGGSGTDFTLTI

SRLEPEDFAVYYCQQYGSSPLTFGGGTKVEIKRAAAGQ

PKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTV

AWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQ

WKSHRSYSCQVTHEGSTVEKTVAPTECS SEQ ID NO:344 eaggtgeage tggtgeagte tggggctgag gtgaagaagc ctgggtcctc ggtaaaggtc 60 tcctgcaagg cttctggagg ccccttccgc aattttgcta tcaactgggt gcgacaggcc 120 cctggacaag ggcttgagtg gatgggaggg ateategetg tctttgggac gacaaagtac 180 gcacataagt tccagggcag agtcaccatc accgcggacg actccacaaa taeagettae 240 atggagctgg gcagcctgaa atetgaggae aeggeegtgt attactgtgc gagaggtccc 300 cactactact cctcctacat ggacgtctgg ggcgaaggga ccacggtcac egtetegagt 360 gctagcacca agggccccag cgtgttcccc ctggccccca geageaagag caccagcggc 420 ggcacagccg ccctgggctg cctggtgaag gactacttcc ccgagcccgt gaeegtgage 480 tggaaeageg gcgccttgac cagcggcgtg cacacottcc ccgccgtgct geagageage 540 ggcctgtaca gcctgagcag cgtggtgacc gtgcccagca gcagcctggg cacccagacc 600 tacatctgca acgtgaacca caagcccagc aacaccaagg tggacaaacg cgtggagccc 660 aagagetgeg acaagaccca cacctgcccc ccctgccctg cccccgagct gctgggcgga 720 ccctccgtgt tcctgttccc ccccaagccc aaggacaccc teatgateag ccggaccccc 780 gaggtgacct gcgtggtggt ggaegtgage cacgaggacc ccgaggtgaa gttcaactgg 840 taegtggaeg gcgtggaggt gcacaacgcc aagaccaagc cccgggagga gcagtacaac 900 agcacctacc gggtggtgag cgtgctcacc gtgctgcacc aggaetgget gaacggcaag 960 gagtacaagt geaaggtgag caacaaggcc ctgcctgccc ccatcgagaa gaccatcagc 1020 aaggccaagg gccagccccg ggagccccag gtgtacaccc tgccccccag ccgggaggag 1080 atgaccaaga accaggtgtc cctcacctgt ctggtgaagg gcttctaccc cagcgacatc 1140 gccgtggagt gggagagcaa cggccagccc gagaacaact acaagaccac cccccctgtg 1200 ctggacagcg aeggeagett cttcctgtac ageaagetea ccgtggacaa gagccggtgg 1260 cagcagggca acgtgttcag ctgcagcgtg atgcacgagg ccctgcacaa ccactacacc 1320 cagaagagcc tgagcctgag ccccggcaag 1350 SEQ ID NO:345

QVQLVQSGAEVKKPGSSVKVSCKASGGPFRNFAINWVR QAPGQGLEWMGGIIAVFGTTKYAHKFQGRVTITADDST NTAYMELGSLKSEDTAVYYCARGPHYYSSYMDVWGEGT TVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDY FPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVT VPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHT CPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVV VDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYR VVSVLTVLHQDWLNGKEYKCKVSNKALPAPI ΕΚΤ I SKA KGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDI AVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK SEQ ID NO:346 gacatccagt tgacccagtc tccatcctcc ctgtctgcat ctgtaggaga cagagtcacc 60 atcacttgcc gggegagtea gggeattage aettatttag cctggtatca gcagaaaccc 120 gggaaagttc ctaaactcct gatetatget gcatccactt tgcaatcagg ggtcccatct 180 eggtteagtg geagtggate tgggacagat ttcactctca ccatcagcag cctgcagcct 240 gaagatgttg caacttatta ctgtcaaaag tataaeagtg ccccttcttt cggccctggg 300 accaaagtgg atatcaaacg tgcggccgca cccagcgtgt tcatcttccc cccctccgac 360 gageagetga agageggeae cgccagcgtg gtgtgcctgc tgaacaactt ctacccccgg 420 gaggccaagg tgcagtggaa ggtggacaac gccctgcaga gcggcaacag ccaggagagc 480 gtgaccgagc aggaeageaa ggactccacc tacagcctga gcagcaccct caccctgagc 540 aaggeegaet aegagaagea caaggtgtac gcctgcgagg tgacccacca gggeetgage 600 agccccgtga ccaagagctt caaccggggc gagtgt 636 SEQ ID NO:347

DIQLTQSPSSLSASVGDRVTITCRASQGISTYLAWYQQ

KPGKVPKLLIYAASTLQSGVPSRFSGSGSGTDFTLTIS

SLQPEDVATYYCQKYNSAPSFGPGTKVDIKRAAAPSVF

IFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNAL

QSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVY

ACEVTHQGLSSPVTKSFNRGEC SEQ ID NO:348 gaggtgcagc tggtggagac tggggctgag gtgaagaagc ctgggtcctc ggtgaaggtc 60 ccctgcaaat cttctggaag ccccttcagg agtaatgctg tcagctgggt gcgacaggcc 120 cccggacaag ggcttgagtg ggtgggagga atcctcggtg tctttggttc accaagctac 180 gcacagaagt tccagggcag agtcacgatt accgcggacg aatccaccaa cacagtccac 240 atggagctga gaggtttgag atctgaggac acggccgtgt attattgtgc gagaggtcct 300 acctactact actcctacat ggacgtctgg ggcaaaggga ccacggtcac cgtctcgagt 360 gctagcacca agggccccag cgtgttcccc ctggccccca gcagcaagag caccagcggc 420 ggcacagccg ccctgggctg cctggtgaag gactacttcc ccgagcccgt gaccgtgagc 480 tggaacagcg gcgccttgac cagcggcgtg cacaccttcc ccgccgtgct gcagagcagc 540 ggcctgtaca gcctgagcag cgtggtgacc gtgcccagca gcagcctggg cacccagacc 600 tacatctgca acgtgaacca caagcccagc aacaccaagg tggacaaacg cgtggagccc 660 aagagctgcg acaagaccca cacctgcccc ccctgccctg cccccgagct gctgggcgga 720 ccctccgtgt tcctgttccc ccccaagccc aaggacaccc tcatgatcag ccggaccccc 780 gaggtgacct gcgtggtggt ggacgtgagc cacgaggacc ccgaggtgaa gttcaactgg 840 tacgtggacg gcgtggaggt gcacaacgcc aagaccaagc cccgggagga gcagtacaac 900 agcacctacc gggtggtgag cgtgctcacc gtgctgcacc aggactggct gaacggcaag 960 gagtacaagt gcaaggtgag caacaaggcc ctgcctgccc ccatcgagaa gaccatcagc 1020 aaggccaagg gccagccccg ggagccccag gtgtacaccc tgccccccag ccgggaggag 1080 atgaccaaga accaggtgtc cctcacctgt ctggtgaagg gcttctaccc cagcgacatc 1140 gccgtggagt gggagagcaa cggccagccc gagaacaact acaagaccac cccccctgtg 1200 ctggacagcg acggcagctt cttcctgtac agcaagctca ccgtggacaa gagccggtgg 1260 cagcagggca acgtgttcag ctgcagcgtg atgcacgagg ccctgcacaa ccactacacc 1320 cagaagagcc tgagcctgag ccccggcaag 1350 SEQ ID NO:349

EVQLVETGAEVKKPGSSVKVPCKSSGSPFRSNAVSWVR

QAPGQGLEWVGGILGVFGSPSYAQKFQGRVTITADEST

NTVHMELRGLRSEDTAVYYCARGPTYYYSYMDVWGKGT

TVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDY

FPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVT

VPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHT

CPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVV

VDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYR

VVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKA

KGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDI avewesngqpennykttppvldsdgsfflyskltvdks

RWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

SEQ ID NO:35Q tcctatgtgc tgactcagcc accctcggag tcagtggccc caggacagac ggccaggatt 60 acctgtgggg gaaataacat tggaagaaat agtgtgcact ggtatcagca gaagccaggc 120 caggcccctg tgctggtcgt gtatgatgat agcgaccggc cctcagggat ccctgagcga 180 ttttctggct ccaagtctgg gaacacggcc accctgatta tcagcagggt cgaagtcggg 240 gatgaggccg actactactg tcaggtgtgg catagtagta gtgatcatta tgtcttcgga 300 actgggacca aggtcaccgt cctaggtgcg gccgcaggcc agcccaaggc cgctcccagc 360 gtgaccctgt tccccccctc ctccgaggag ctgcaggcca acaaggccac cctggtgtgc 420 ctcatcagcg acttctaccc tggcgccgtg accgtggcct ggaaggccga cagcagcccc 480 gtgaaggccg gcgtggagac caccaccccc agcaagcaga gcaacaacaa gtacgccgcc 540 agcagctacc tgagcctcac ccccgagcag tggaagagcc accggagcta cagctgccag 600 gtgacccacg agggcagcac cgtggagaag accgtggccc ccaccgagtg cage 654 SEQ ID NO:351

SYVLTQPPSESVAPGQTARITCGGNNIGRNSVHWYQQK

PGQAPVLVVYDDSDRPSGIPERFSGSKSGNTATLIISR

VEVGDEADYYCQVWHSSSDHYVFGTGTKVTVLGAAAGQ

PKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTV

AWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQ

WKSHRSYSCQVTHEGSTVEKTVAPTECS SEQ ID NO:352 eagatgeage tggtacaatc tggagetgag gtgaagaagc ctgggtcctc ggtgaaggtc 60 tcctgcaagg cttctggagg caccttcagc agetatgeta tcagctgggt gcgacaggcc 120 cctggacaag ggcttgagtg gatgggaggg atetteggta tgtttgggac agcaaactac 180 gegeagaagt tccagggcag agtcacgatt accgcggacg aatteaegag cgcggcctac 240 atggagctga gcagcctggg atctgaggac acggccatgt attactgtgc gaggtetagt 300 ggttattacc cccaatactt ccaggactgg ggccagggca ccctggtcac cgtctcgagt 360 gctagcacca agggccccag cgtgttcccc ctggccccca gcagcaagag caccagcggc 420 ggcacagccg ccctgggctg cctggtgaag gactacttcc ccgagcccgt gaccgtgagc 480 tggaacagcg gcgccttgac cagcggcgtg cacaccttcc ccgccgtgct gcagagcagc 540 ggcctgtaca gcctgagcag cgtggtgacc gtgcccagca gcagcctggg cacccagacc 600 tacatctgca acgtgaacca caagcccagc aacaccaagg tggacaaacg cgtggagccc 660 aagagctgcg acaagaccca cacctgcccc ccctgccctg cccccgagct gctgggcgga 720 ccctccgtgt tcctgttccc ccccaagccc aaggacaccc tcatgatcag ccggaccccc 780 gaggtgacct gcgtggtggt ggacgtgagc cacgaggacc ccgaggtgaa gttcaactgg 840 tacgtggacg gcgtggaggt gcacaacgcc aagaccaagc cccgggagga gcagtacaac 900 agcacctacc gggtggtgag cgtgctcacc gtgctgcacc aggactggct gaacggcaag 960 gagtacaagt gcaaggtgag caacaaggcc ctgcctgccc ccatcgagaa gaccatcagc 1020 aaggccaagg gccagccccg ggagccccag gtgtacaccc tgccccccag ccgggaggag 1080 atgaccaaga accaggtgtc cctcacctgt ctggtgaagg gcttctaccc cagcgacatc 1140 gccgtggagt gggagagcaa cggccagccc gagaacaact acaagaccac cccccctgtg 1200 ctggacagcg acggcagctt cttcctgtac agcaagctca ccgtggacaa gagccggtgg 1260 cagcagggca acgtgttcag ctgcagcgtg atgcacgagg ccctgcacaa ccactacacc 1320 cagaagagcc tgagcctgag ccccggcaag 1350 SEQ ID NO:353

O MQ L vo S G A E V K K P G S S V K V S C K A S G G T F 5 S Ϊ A I 5 W VR QAPGQGLEWMGGIFGMFGTANYAQKFQGRVTITADEFT SAAYMELSSLGSEDTAMYYCARSSGYYPQYFQDWGQGT LVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDY FPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVT VPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHT CPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVV VDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYR VVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKA KGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDI AVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK SEQ ID NO:354 gaaattgtga tgacacagtc tccaggcacc ctgtctttgt ctccagggca aagagccacc 60 ctctcctgca gggccagtca gagtgttagc agcagctact tagcctggta ccagcagaaa 120 cctggccagg ctcccagact cctcatgtat ggtgcatcca gcagggccac tggcatccca 180 gacaggttca gtggcagtgg gtctgggaca gacttcactc tcaccatcag cagactggag 240 cetgaagatt ttgcagtgta ttactgtcag cagtatggta gctcatcgct cactttcggc 300 ggagggacca agctggagat caaacgtgcg gccgcaccca gcgtgttcat cttccccccc 360 tccgacgagc agctgaagag cggcaccgcc agcgtggtgt gcctgctgaa caacttctac 420 ccccgggagg ccaaggtgca gtggaaggtg gacaacgccc tgcagagcgg caacagccag 480 gagagcgtga ccgagcagga cagcaaggac tccacctaca gcctgagcag caccctcacc 540 ctgagcaagg ccgactacga gaagcacaag gtgtacgcct gcgaggtgac ccaccagggc 600 ctgagcagcc ccgtgaccaa gagcttcaac cggggcgagt gt 642 SEQ ID NO:355

EIVMTQSPGTLSLSPGQRATLSCRASQSVSSSYLAWYQ

QKPGQAPRLLMYGASSRATGIPDRFSGSGSGTDFTLTI

SRLEPEDFAVYYCQQYGSSSLTFGGGTKLEIKRAAAPS

VFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDN alqsgnsqesvteqdskdstyslsstltlskadyekhk

VYACEVTHQGLSSPVTKSFNRGEC SEQ ID NO:356 gaggtgcagc tggtggagtc cggggctgag gtgaagaagc ctgggtcctc ggtgaaggtc 60 tcctgcaagg cttctggagg catcttcaac agttatgcta tcagctgggt gcgacaggcc 120 cctggacaag ggcttgagtg gatgggaggc atcatcgcta tctttcatac accaaagtac 180 gcacagaagt tccagggcag agtcacgatt accgcggacg aatccacgaa cacagcctac 240 atggaactga gaagcctgaa atctgaggac acggccctgt attactgtgc gagagggtcc 300 acttacgatt tttcgagtgg ccttgactac tggggccagg gaaccctggt caccgtctcg 360 agtgctagca ccaagggccc cagcgtgttc cccctggccc ccagcagcaa gagcaccagc 420 ggcggcacag ccgccctggg ctgcctggtg aaggactact tccccgagcc cgtgaccgtg 480 agctggaaca gcggcgcctt gaccagcggc gtgcacacct tccccgccgt gctgcagagc 540 agcggcctgt acagcctgag cagcgtggtg accgtgccca gcagcagcct gggcacccag 600 acctacatct gcaacgtgaa ccacaagccc agcaacacca aggtggacaa acgcgtggag 660 cccaagagct gcgacaagac ccacacctgc cccccctgcc ctgcccccga gctgctgggc 720 ggaccctccg tgttcctgtt cccccccaag cccaaggaca ccctcatgat cagccggacc 780 cccgaggtga cctgcgtggt ggtggacgtg agccacgagg accccgaggt gaagttcaac 840 tggtacgtgg acggcgtgga ggtgcacaac gccaagacca agccccggga ggagcagtac 900 aacagcacct accgggtggt gagcgtgctc accgtgctgc accaggactg gctgaacggc 960 aaggagtaca agtgcaaggt gagcaacaag gccctgcctg cccccatcga gaagaccatc 1020 agcaaggcca agggccagcc ccgggagccc caggtgtaca ccctgccccc cagccgggag 1080 gagatgacca agaaccaggt gtccctcacc tgtctggtga agggcttcta occcagcgac 1140 atcgccgtgg agtgggagag caacggccag cccgagaaca actacaagac caccccccct 1200 gtgctggaca gcgacggcag cttcttcctg tacagcaagc tcaccgtgga caagagccgg 1260 tggcagcagg gcaacgtgtt cagctgcagc gtgatgcacg aggccctgca caaccactac 1320 acccagaaga gcctgagcct gagccccggc aag 1353 SEQ ID NO:357

EVQLVESGAEVKKPGSSVKVSCKASGGIFNSYAISWVR QAPGQGLEWMGGIIAIFHTPKYAQKFQGRVTITADEST NTAYMELRSLKSEDTALYYCARGSTYDFSSGLDYWGQG T LVTVS SASTKGPSVFPLAPS SKST SGGTAALGCLVKD YFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVV TVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTH TCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCV VVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTY RVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISK AKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSD IAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDK SRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK SEQ ID NO:358 caggcagggc tgactcagcc accctcggtg tcagtggccc caggacagac ggccaggatt 60 acctgtgggg gaaacaacat tggaagtaaa agtgtgcact ggtaccagca gaagccaggc 120 caggcccctg tcctagtcgt ctatgatgat agcgaccggc cctcagggat ccctgagcga 180 ttctctggct ccaactctgg gaacacggcc accctgacca tcagcagggt cgaagccggg 240 gatgaggccg actattactg tcaggtgtgg gatagtagta gtgatcatgt ggtattcggc 300 ggagggacca agctgaccgt cctaggtgcg gccgcaggcc agcccaaggc cgctcccagc 360 gtgaccctgt tccccccctc ctccgaggag ctgcaggcca acaaggccac cctggtgtgc 420 ctcatcagcg acttctaccc tggcgccgtg accgtggcct ggaaggccga cagcagcccc 480 gtgaaggccg gcgtggagac caccaccccc agcaagcaga gcaacaacaa gtacgccgcc 540 agcagctacc tgagcctcac ccccgagcag tggaagagcc accggagcta cagctgccag 600 gtgacccacg agggcagcac cgtggagaag accgtggccc ccaccgagtg cage 654 SEQ ID NO:359

QAGLTQPPSVSVAPGQTARITCGGNNIGSKSVHWYQQK

PGQAPVLVVYDDSDRPSGIPERFSGSNSGNTATLTISR veagdeadyycqvwdsssdhvvfgggtkltvlgaaagq

PKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTV awkadsspvkagvetttpskqsnnkyaassylsltpeq

WKSHRSYSCQVTHEGSTVEKTVAPTECS

SEQ ID NO:36Q caggtccagc tggtgcagtc tggggctgag gtgaagaagc ctgggtcctc ggtgaaggtc 60 tcctgcaagg cttctggagg cttcttcagc agctatgcta tcagctgggt gcgccaggcc 120 cctggacaag gacttgagtg gatggggggg gtcatcccta tctttcgtac agcaaactac 180 gcacagaact tccagggcag agtcaccatt accgcggacg aattcacatc gtatatggag 240 ctgagcagcc tgagatctga cgacacggcc gtgtattact gtgcgaggtt gaattaccat 300 gattcgggga cttattataa cgccccccgg ggctggttcg acccctgggg ccagggaacc 360 ctggtcaccg tctcgagtgc tagcaccaag ggccccagcg tgttccccct ggcccccagc 420 agcaagagca ccagcggcgg cacagccgcc ctgggctgcc tggtgaagga ctacttcccc 480 gagcccgtga ccgtgagctg gaacagcggc gccttgacca gcggcgtgca caccttcccc 540 gccgtgctgc agagcagcgg cctgtacagc ctgagcagcg tggtgaccgt gcccagcagc 600 agcctgggca cccagaccta catctgcaac gtgaaccaca agcccagcaa caccaaggtg 660 gacaaacgcg tggagcccaa gagctgcgac aagacccaca cctgcccccc ctgccctgcc 720 cccgagctgc tgggcggacc ctccgtgttc ctgttccccc ccaagcccaa ggacaccctc 780 atgatcagcc ggacccccga ggtgacctgc gtggtggtgg acgtgagcca cgaggacccc 840 gaggtgaagt tcaactggta cgtggacggc gtggaggtgc acaacgccaa gaccaagccc 900 cgggaggagc agtacaacag cacctaccgg gtggtgagcg tgctcaccgt gctgcaccag 960 gactggctga acggcaagga gtacaagtgc aaggtgagca acaaggccct gcctgccccc 1020 atcgagaaga ccatcagcaa ggccaagggc cagccccggg agccccaggt gtacaccctg 1080 ccccccagcc gggaggagat gaccaagaac caggtgtccc tcacctgtct ggtgaagggc 1140 ttctacccca gcgacatcgc cgtggagtgg gagagcaacg gccagcccga gaacaactac 1200 aagaccaccc cccctgtgct ggacagcgac ggcagcttct tcctgtacag caagctcacc 1260 gtggacaaga gccggtggca gcagggcaac gtgttcagct gcagcgtgat gcacgaggcc 1320 ctgcacaacc actacaccca gaagagcctg agcctgagcc ccggcaag 1368 SEQ ID NO:361

QVQLVQSGAEVKKPGSSVKVSCKASGGFFSSYAISWVR

QAPGQGLEWMGGVIPIFRTANYAQNFQGRVTITADEFT

SYMELSSLRSDDTAVYYCARLNYHDSGTYYNAPRGWFD pwgqgtlvtvssastkgpsvfplapsskstsggtaalg

CLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYS

LSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKS

CDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTP

EVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQ

YNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIE

KTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKG

FYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSK

LTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK SEQ ID NO:362 gacatccaga tgacccagtc tccagactcc ctggctgtgt ctctgggcga gaaggccacc 60 atcaactgca agtccagcca gagtatttta aacagctcca acaataagaa ctacttagct 120 tggtaccagc agaaaccagg acagcctcct aagctgctca tttactgggc atctacccgg 180 gaatccgggg tccctgaccg attcagtggc agcgggtctg ggacagattt cactctcacc 240 atcagcagcc tgcaggctga agatgtggca gtttattact gtcagcaata ttatagtagt 300 ccgccgacgt tcggccaagg gaccaaggtg gaaatcaaac gtgcggccgc acccagcgtg 360 ttcatcttcc ccccctccga cgagcagctg aagagcggca ccgccagcgt ggtgtgcctg 420 ctgaacaact tctacccccg ggaggccaag gtgcagtgga aggtggacaa cgccctgcag 480 agcggcaaca gccaggagag cgtgaccgag caggacagca aggactccac ctacagcctg 540 agcagcaccc tcaccctgag caaggccgac tacgagaagc acaaggtgta cgcctgcgag 600 gtgacccacc agggcctgag cagccccgtg accaagagct tcaaccgggg cgagtgt 657 SEQ ID NO:363

DIQMTQSPDSLAVSLGEKATINCKSSQSILNSSNNKNY lawyqqkpgqppklliywastresgvpdrfsgsgsgtd ftltisslqaedvavyycqqyysspptfgqgtkveikr aaapsvfifppsdeqlksgtasvvcllnnfypreakvq wkvdnalqsgnsqesvteqdskdstyslsstltlskad

YEKHKVYACEVTHQGLSSPVTKSFNRGEC SEQ ID NO:364 caggtccagc tggtgcagtc tggagctgag gtgaagaagc ctgggtcctc ggtgaaggtc 60 tcctgcaagg cttctggagt caccttcagt tactatgcta tgagctgggt gcgacaggcc 120 cctggacaag ggcttgagtg gatgggagga atcagcccta tgtttgggac aacaacctac 180 gcacagaagt tccagggcag agtcacgatt actgcggacg actccacgag tacagcctac 240 atggaggtga ggagcctgag atctgaggac acggccgtgt attactgtgc gagatcttcg 300 aattactatg atagtgtata tgactactgg ggccagggaa ccctggtcac cgtctcgagt 360 gctagcacca agggccccag cgtgttcccc ctggccccca gcagcaagag caccagcggc 420 ggcacagccg ccctgggctg cctggtgaag gactacttcc ccgagcccgt gaccgtgagc 480 tggaacagcg gcgccttgac cagcggcgtg cacaccttcc ccgccgtgct gcagagcagc 540 ggcctgtaca gcctgagcag cgtggtgacc gtgcccagca gcagcctggg cacccagacc 600 tacatctgca acgtgaacca caagcccagc aacaccaagg tggacaaacg cgtggagccc 660 aagagctgcg acaagaccca cacctgcccc ccctgccctg cccccgagct gctgggcgga 720 ccctccgtgt tcctgttccc ccccaagccc aaggacaccc tcatgatcag ccggaccccc 780 gaggtgacct gcgtggtggt ggacgtgagc cacgaggacc ccgaggtgaa gttcaactgg 840 tacgtggacg gcgtggaggt gcacaacgcc aagaccaagc cccgggagga gcagtacaac 900 agcacctacc gggtggtgag cgtgctcacc gtgctgcacc aggactggct gaacggcaag 960 gagtacaagt gcaaggtgag caacaaggcc ctgcctgccc ccatcgagaa gaccatcagc 1020 aaggccaagg gccagccccg ggagccccag gtgtacaccc tgccccccag ccgggaggag 1080 atgaccaaga accaggtgtc cctcacctgt ctggtgaagg gcttctaccc cagcgacatc 1140 gccgtggagt gggagagcaa cggccagccc gagaacaact acaagaccac cccccctgtg 1200 ctggacagcg acggcagctt cttcctgtac agcaagctca ccgtggacaa gagccggtgg 1260 cagcagggca acgtgttcag ctgcagcgtg atgcacgagg ccctgcacaa ccactacacc 1320 cagaagagcc tgagcctgag ccccggcaag 1350 SEQ ID NO:365

QVQLVQSGAEVKKPGSSVKVSCKASGVTFSYYAMSWVR qapgqglewmggispmfgtttyaqkfqgrvtitaddst

STAYMEVRSLRSEDTAVYYCARSSNYYDSVYDYWGQGT

LVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDY

FPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVT

VPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHT

CPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVV

VDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYR

VVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKA

KGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDI

AVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKS

RWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK SEQ ID NO:366 cagtctgtcg tgacgcagcc gccctcggag tcagtggccc caggacagac ggccaggatt 60 acctgtgggg gacataacat tggaagtaat agtgtgcact ggtaccagca gaagccaggc 120 caggcccctg tgctggtcgt gtatgataat agcgaccggc cctcagggat ccctgagcga 180 ttctctggct ccaactctgg gaacacggcc accctgacca tcagcagggt cgaagccggg 240 gatgaggccg actattactg tcaggtgtgg ggtagtagta gtgaccatta tgtcttcgga 300 actgggacca aggtcaccgt cctaggtgcg gccgcaggcc agcccaaggc cgctcccagc 360 gtgaccctgt tccccccctc ctccgaggag ctgcaggcca acaaggccac cctggtgtgc 420 ctcatcagcg acttctaccc tggcgccgtg accgtggcct ggaaggccga cagcagcccc 480 gtgaaggccg gcgtggagac caccaccccc agcaagcaga gcaacaacaa gtacgccgcc 540 agcagetacc tgagcctcac ccccgagcag tggaagagcc accggagcta cagctgccag 600 gtgacccacg agggcagcac cgtggagaag accgtggccc ccaccgagtg cage 654 SEQ ID NO:367 qsvvtqppsesvapgqtaritcgghnxgsnsvhwyqqk pgqapvlvvydnsdrpsgiperfsgsnsgntatltisr

VEAGDEADYYCQVWGSSSDHYVFGTGTKVTVLGAAAGQ pkaapsvtlfppsseelqankatlvclisdfypgavtv

AWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQ

WKSHRSYSCQVTHEGSTVEKTVAPTECS

Table 1: First round Vkappa, Vlambda and VH amplifications

Table 2: Second round Vkappa, Vlambda and VH amplifications

Table 3. Second round VL regions amplification overview

Table 5: Characteristics of the individual IgM memory B cell libraries.

i aoie «. uata ot tne MA-specmc igus.

Table 9. Binding of IgGs to HA (H5N1TV)-expressing PER.C6 cells.

Table 21. Respiratory distress of mice infected with H1N1 virus and treated with antibody at different time points prior- and postinfection

Table 22. Sequence of HA2 epitope in different influenza subtypes. The underlined amino acid represents the valine (V) -> glutamic acid (E) substitution in the H2N2 escape mutant (mutant

II; Table 13)

REFERENCES

[0146]

Boel E et al. (2000), Functional human monoclonal antibodies of all isotypes constructed from phage display library-derived single-chain Fv antibody fragments. J. Immunol. Methods 239:153-166

Burton DR and Barbas CF (1994), Fluman antibodies from combinatorial libraries. Adv. Immunol. 57:191-280

Chou TC and P Talalay (1984) Quantitative analysis of dose-effect relationships: the combined effects of multiple drugs or enzyme inhibitors. Adv Enzyme Regul 22:27-55

De Kruif J et al. (1995a), Rapid selection of cell subpopulation-specific human monoclonal antibodies from a synthetic phage antibody library. Proc Natl Acad Sci USA 92:3938

De Kruif J et al. (1995b) Selection and application of human single-chain Fv antibody fragments from a semi-synthetic phage antibody display library with designed CDR3 regions. J. Mol. Biol. 248:97-105.

Huls G et al. (1999) Antitumor immune effector mechanisms recruited by phage display-derived fully human lgG1 and lgA1 monoclonal antibodies. Cancer Res 59:5778-5784

Okuno Y et al (1993) A common neutralizing epitope conserved between the hemagglutinins of Influenza A virus H1 and H2 strains. J. Virol. 67:2552-2558.

Slootstra JW et al. (1996) Structural aspects of antibody-antigen interaction revealed through small random peptide libraries. Mol. Divers. 1:87-96.

Smirnov YAet al (1999) An epitope shared by the hemagglutinins of H1, H2, H5 and H6 subtypes of influenza A virus. Acta Virol. 43:237-244.

The World Health Organization Global Influenza Program Surveillance Network (2005), Evolution of H5N1 Avian Influenza Viruses in Asia. Emerg Infect Dis 11:1515-1521

SEQUENCE LISTING

[0147]

<110> Crucell Holland B.V. Van den Brink, Edward N Throsby, Mark De Kruif, Cornells A <120> Human binding molecules capable of neutralizing influenza virus H5N1 and uses thereof

<130 0145 WO 00 ORD <140 PCT/EP2007/059356 <141> 2007-09-06 <150> US 60/842,930 <151 >2006-09-07 <150> EP 06120316.2 <151 >2006-09-07 <150 EP 06120644.7 <151 >2006-09-14 <150 EP 06125107.0 <151> 2006-11-30 <150 EP 07111235.3 <151 >2007-06-28 <160 377 <170> Patentln version 3.3 <210> 1 <211 > 5

<212> PRT <213> Homo sapiens <400> 1

Ser Tyr Ala Ile Ser 1 5 <210> 2 <211> 17

<212> PRT <213> Homo sapiens <400>2

Gly Ile Ile Pro Ile Phe Gly Thr Thr Lys Tyr Ala Pro Lys Phe Gin 15 10 15

Gly <210> 3 <211 > 12

<212> PRT <213> Homo sapiens <400>3

His Met Gly Tyr Gin Val Arg Glu Thr Met Asp Val 15 10 <210> 4 <211 > 13

<212> PRT <213> Homo sapiens <400>4

Ser Gly Ser Thr Phe Asn Ile Gly Ser Asn Ala Val Asp 15 10 <210>5 <211 > 7

<212> PRT <213> Homo sapiens <400>5

Ser Asn Asn Gin Arg Pro Ser 1 5 <210> 6 <211 > 11

<212> PRT <213> Homo sapiens <400>6

Ala Ala Trp Asp Asp Ile Leu Asn Val Pro Val 15 10 <210>7 <211 > 14

<212> PRT <213> Homo sapiens <400>7

Thr Gly Thr Ser Ser Asp Val Gly Gly Tyr Asn Tyr Val Ser 15 10 <210> 8 <211 > 7

<212> PRT <213> Homo sapiens <400>8

Glu Val Ser Asn Arg Pro Ser 1 5 <210>9 <211 > 10

<212> PRT <213> Homo sapiens <400>9

Ser Ser Tyr Thr Ser Ser Ser Thr Tyr Val 15 10 <210> 10 <211 > 13

<212> PRT <213> Homo sapiens <400> 10

Ser Gly Ser Arg Ser Asn Val Gly Asp Asn Ser Val Tyr 15 10 <210> 11 <211 > 7

<212> PRT <213> Homo sapiens <400> 11

Lys Asn Thr Gin Arg Pro Ser 1 5 <210> 12 <211 > 11

<212> PRT <213> Homo sapiens <400> 12

Val Ala Trp Asp Asp Ser Val Asp Gly Tyr Val 15 10 <210> 13 <211 > 13

<212> PRT <213> Homo sapiens <400> 13

Ser Gly Ser Ser Ser Asn Ile Gly Asn Asp Tyr Val Ser 15 10 <210> 14 <211 > 7

<212> PRT <213> Homo sapiens <400> 14

Asp Asn Asn Lys Arg Pro Ser 1 5 <210> 15 <211 > 12

<212> PRT <213> Homo sapiens <400> 15

Ala Thr Trp Asp Arg Arg Pro Thr Ala Tyr Val Val 15 10 <210> 16 <211 > 5

<212> PRT <213> Homo sapiens <400> 16

Gly Ser Ala Ile Ser 1 5 <210> 17 <211> 17

<212> PRT <213> Homo sapiens <400> 17

Gly Ile Ser Pro Leu Phe Gly Thr Thr Asn Tyr Ala Gin Lys Phe Gin 15 10 15

Gly <210> 18 <211 > 11

<212> PRT <213> Homo sapiens <400> 18

Gly Pro Lys Tyr Tyr Ser Glu Tyr Met Asp Val 15 10 <210> 19 <211 > 11

<212> PRT <213> Homo sapiens <400> 19

Arg Ala Ser Gin Gly Ile Ser Ser Tyr Leu Ala 15 10 <210> 20 <211 > 7

<212> PRT <213> Homo sapiens <400> 20

Asp Ala Ser Thr Leu Arg Ser 1 5 <210>21 <211> 10

<212> PRT <213> Homo sapiens <400> 21

Gin Arg Tyr Asn Ser Ala Pro Pro Ile Thr 15 10 <210> 22 <211 > 17

<212> PRT <213> Homo sapiens <400> 22

Gly Ile Met Gly Met Phe Gly Thr Thr Asn Tyr Ala Gin Lys Phe Gin 15 10 15

Gly <210> 23 <211 > 11

<212> PRT <213> Homo sapiens <400> 23

Ser Ser Gly Tyr Tyr Fro Glu Tyr Fhe Gin Asp 15 10 <210> 24 <211> 11

<212> PRT <213> Homo sapiens <400> 24

Ser Gly His Lys Leu Gly Asp Lys Tyr Val Ser 15 10 <210> 25 <211 > 7

<212> PRT <213> Homo sapiens <400> 25

Gin Asp Asn Arg Arg Fro Ser 1 5 <210> 26 <211 > 9

<212> PRT <213> Homo sapiens <400> 26

Gin Ala Trp Asp Ser Ser Thr Ala Val 1 5 <210> 27 <211 > 5

<212> PRT <213> Homo sapiens <400> 27

Ser Tyr Ser Met Asn 1 5 <210> 28 <211 > 17

<212> PRT <213> Homo sapiens <400> 28

Ser Ile Ser Ser Ser Ser Ser Tyr Ile Tyr Tyr Val Asp Ser Val Lys 15 10 15

Gly <210> 29 <211 > 13

<212> PRT <213> Homo sapiens <400> 29

Gly Gly Gly Ser Tyr Gly Ala Tyr Glu Gly Phe Asp Tyr 15 10 <210> 30 <211 > 11

<212> PRT <213> Homo sapiens <400> 30

Arg Ala Ser Gin Arg Val Ser Ser Tyr Leu Ala 15 10 <210> 31 <211 > 7

<212> PRT <213> Homo sapiens <400> 31

Gly Ala Ser Thr Arg Ala Ala 1 5 <210> 32 <211 > 9

<212> PRT <213> Homo sapiens <400> 32

Gin Gin Tyr Gly Arg Thr Pro Leu Thr 1 5 <210> 33 <211> 11

<212> PRT <213> Homo sapiens <400> 33

Gly Gly Asn Asn Ile Gly Ser Lys Ser Val His 15 10 <210> 34 <211 > 7

<212> PRT <213> Homo sapiens <400> 34

Asp Asp Ser Asp Arg Pro Ser 1 5 <210> 35 <211 > 11

<212> PRT <213> Homo sapiens <400> 35

Gin Val Trp Asp Ser Ser Ser Asp His Ala Val 15 10 <210> 36 <211 > 13

<212> PRT <213> Homo sapiens <400> 36

Ser Gly Ser Ser Ser Asn Ile Gly Ser Asn Tyr Val Tyr 15 10 <210> 37 <211 > 7

<212> PRT <213> Homo sapiens <400> 37

Arg Asp Gly Gin Arg Pro Ser 1 5 <210> 38 <211 > 11

<212> PRT <213> Homo sapiens <400> 38

Ala Thr Trp Asp Asp Asn Leu Ser Gly Pro Val 15 10 <210> 39 <211 > 5

<212> PRT <213> Homo sapiens <400> 39

Ser Tyr Gly Ile Ser 1 5 <210> 40 <211 > 17

<212> PRT <213> Homo sapiens <400> 40

Asp Ile Ile Gly Met Phe Gly Ser Thr Asn Tyr Ala Gin Asn Phe Gin 15 10 15

Gly <210> 41 <211 > 11

<212> PRT <213> Homo sapiens <400> 41

Ser Ser Gly Tyr Tyr Pro Ala Tyr leu Pro His 15 10 <210> 42 <211 > 12

<212> PRT <213> Homo sapiens <400> 42

Arg Ala Ser Gin Ser Val Ser Ser Ser Tyr Leu Ala 15 10 <210> 43 <211 > 7

<212> PRT <213> Homo sapiens <400> 43

Gly Ala Ser Ser Arg Ala Thr 1 5 <210> 44 <211 > 9

<212> PRT <213> Homo sapiens <400> 44

Gin Gin Tyr Gly Ser Ser Pro Arg Thr 1 5 <210> 45 <211 > 5

<212> PRT <213> Homo sapiens <400> 45

Phe Tyr Ser Met Ser 1 5 <210> 46 <211 > 17

<212> PRT <213> Homo sapiens <400> 46

Gly Ile Ile Pro Met Phe Gly Thr Thr Asn Tyr Ala Gin Lys Phe Gin 15 10 15

Gly <210> 47 <211 > 12

<212> PRT <213> Homo sapiens <400> 47

Gly Asp Lys Gly Ile Tyr Tyr Tyr Tyr Met Asp Val 15 10 <210> 48 <211 > 10

<212> PRT <213> Homo sapiens <400> 48

Ser Ser Tyr Thr Ser Ser Ser Thr Len Val 15 10 <210> 49 <211 > 17

<212> PRT <213> Homo sapiens <400> 49

Gly Ile Ile Gly Met Phe Gly Thr Ala Asn Tyr Ala Gin Lys Phe Gin 15 10 15

Gly <210> 50 <211 > 11

<212> PRT <213> Homo sapiens <400> 50

Gly Asn Tyr Tyr Tyr Glu Ser Ser Leu Asp Tyr 15 10 <210>51 <211> 11

<212> PRT <213> Homo sapiens <400> 51

Gin Val Trp Asp Ser Ser Ser Asp His Tyr Val 15 10 <210> 52 <211 > 5

<212> PRT <213> Homo sapiens <400> 52

Asn Tyr Ala Met Ser 1 5 <210> 53 <211 > 17

<212> PRT <213> Homo sapiens <400> 53

Gly Ile Ile Ala Ile Phe Gly Thr Pro Lys Tyr Ala Gin Lys Phe Gin 15 10 15

Gly <210> 54 <211 > 14

<212> PRT <213> Homo sapiens <400> 54

Ile Pro His Tyr Asn Phe Gly Ser Gly Ser Tyr Phe Asp Tyr 15 10 <210> 55 <211 > 14

<212> PRT <213> Homo sapiens <400> 55

Thr Gly Ser Ser Ser Asn Ile Gly Ala Gly Tyr Asp Val His 15 10 <210> 56 <211 > 7

<212> PRT <213> Homo sapiens <400> 56

Gly Asn Ser Asn Arg Pro Ser 1 5 <210> 57 <211 > 11

<212> PRT <213> Homo sapiens <400> 57

Gly Thr Trp Asp Ser Ser Leu Ser Ala Tyr Val 15 10 <210> 58 <211> 1353

<212> DNA <213> Homo sapiens <220> <221 > CDS <222> (1)..(1353) <400> 58 gag gtg cag ctg gtg gag tct ggg get gag gtg aag aag cct ggg tee 4 8

Glu Val Gin Leu Val Glu Ser Gly Ala Glu Val Lys Lys Pro Gly Ser 15 10 15 teg gtg aaa gtc tct tgc aag get tct gga ggc ccc ttc ege age tat 96

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Pro Phe Arg Ser Tyr 20 25 30 get ate age tgg gtg ega cag gcc cct gga caa ggg cct gag tgg atg 144

Ala Ile Ser Trp Val Arg Gin Ala Pro Gly Gin Gly Pro Glu Trp Met 35 40 45 gga ggg atc atc cct att ttt ggt aca aca aaa tac gca ccg aag ttc 192

Gly Gly Ile Ile Pro Ile Phe Gly Thr Thr Lys Tyr Ala Pro Lys Phe 50 55 60 cag ggc aga gtc acg att acc gcg gac gat ttc gcg ggc aca gtt tac 240

Gin Gly Arg Val Thr Ile Thr Ala Asp Asp Phe Ala Gly Thr Val Tyr 65 70 75 80 atg gag ctg age age ctg ega tet gag gac acg gcc atg tac tac tgt 288

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Met Tyr Tyr Cys 85 90 95 gcg aaa cat atg ggg tac cag gtg ege gaa act atg gac gtc tgg ggc 336

Ala Lys His Met Gly Tyr Gin Val Arg Glu Thr Met Asp Val Trp Gly 100 105 110 aaa ggg acc acg gtc acc gtc teg agt get age acc aag ggc ccc age 384

Lys Gly Thr Thr Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser 115 120 125 gtg ttc ccc ctg gcc ccc age age aag age acc age ggc ggc aca gcc 432

Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala 130 135 140 gcc ctg ggc tgc ctg gtg aag gac tac ttc ccc gag ccc gtg acc gtg 480

Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val 145 150 155 160 age tgg aac age ggc gcc ttg acc age ggc gtg cac acc ttc ccc gcc 528

Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala 165 170 175 gtg ctg cag age age ggc ctg tac age ctg age age gtg gtg acc gtg 576

Val Leu Gin Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val 180 185 190 ccc age age age ctg ggc acc cag acc tac atc tgc aac gtg aac cac 624

Pro Ser Ser Ser Leu Gly Thr Gin Thr Tyr Ile Cys Asn Val Asn His 195 200 205 aag ccc age aac acc aag gtg gac aaa ege gtg gag ccc aag age tgc 672

Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser Cys 210 215 220 gac aag acc cac acc tgc ccc ccc tgc cct gcc ccc gag ctg ctg ggc 720

Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly 225 230 235 240 gga ccc tee gtg ttc ctg ttc ccc ccc aag ccc aag gac acc etc atg 768

Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met 245 250 255 ate age egg acc ccc gag gtg acc tgc gtg gtg gtg gac gtg age cac 816

Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His 260 265 270 gag gac ccc gag gtg aag ttc aac tgg tac gtg gac ggc gtg gag gtg 864

Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val 275 280 285 cac aac gcc aag acc aag ccc egg gag gag cag tac aac age acc tac 912

His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gin Tyr Asn Ser Thr Tyr 290 295 300 egg gtg gtg age gtg etc ace gtg ctg cac cag gac tgg ctg aac ggc 960

Arg Val Val Ser Val Leu Thr Val Leu His Gin Asp Trp Leu Asn Gly 305 310 315 320 aag gag tac aag tgc aag gtg age aac aag gee ctg cct gee ccc ate 1005

Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro lie 325 330 335 gag aag ace ate age aag gee aag gge eag ccc egg gag ecc cag gtg 1056

Glu Lys Thr Ile Ser Lys Ala Lys Gly Gin Pro Arg Glu Pro Gin Val 340 345 350 tac ace ctg ccc ccc age egg gag gag atg acc aag aac cag gtg tee 1104

Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gin Val Ser 355 360 365 etc acc tgt ctg gtg aag ggc ttc tac ccc age gac ate gee gtg gag 1152

Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp lie Ala Val Glu 370 375 380 tgg gag age aac ggc cag ccc gag aac aac tac aag acc acc ccc cct 1200

Trp Glu Ser Asn Gly Gin Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro 385 390 395 400 gtg ctg gac age gac ggc age ttc ttc ctg tac age aag etc acc gtg 1248

Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val 405 410 415 gac aag age egg tgg cag cag ggc aac gtg ttc age tgc age gtg atg 1296

Asp Lys Ser Arg Trp Gin Gin Gly Asn Val Phe Ser Cys Ser Val Met 420 425 430 cac gag gee ctg cac aac cac tac acc cag aag age ctg age ctg age 1344

His Glu Ala Leu His Asn His Tyr Thr Gin Lys Ser Leu Ser Leu Ser 435 440 445 ccc ggc aag 1353

Pro Gly Lys 450 <210> 59 <211 > 451

<212> PRT <213> Homo sapiens <400> 59

Glu Val Gin Leu Val Glu Ser Gly Ala Glu Val Lys Lys Pro Gly Ser 15 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Pro Phe Arg Ser Tyr 20 25 30

Ala lie Ser Trp Val Arg Gin Ala Pro Gly Gin Gly Pro Glu Trp Met 35 40 45

Gly Gly lie lie Pro lie Phe Gly Thr Thr Lys Tyr Ala Pro Lys Phe 50 55 60

Gin Gly Arg Val Thr lie Thr Ala Asp Asp Phe Ala Gly Thr Val Tyr 65 70 75 80

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Met Tyr Tyr Cys 85 90 95

Ala Lys His Met Gly Tyr Gin Val Arg Glu Thr Met Asp Val Trp Gly 100 105 110

Lys Gly Thr Thr Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser 115 120 125

Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala 130 135 140

Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val 145 150 155 160

Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala 165 170 175

Val Leu Gin Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val 180 185 190

Pro Ser Ser Ser Leu Gly Thr Gin Thr Tyr Ile Cys Asn Val Asn His 195 200 205

Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser Cys 210 215 220

Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly 225 230 235 240

Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met 245 250 255

Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Sar His 260 265 270

Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val 275 280 285

His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gin Tyr Asn Ser Thr Tyr 290 295 300

Arg Val Val Ser Val Leu Thr Val Leu His Gin Asp Trp Leu Asn Gly 305 310 315 320

Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile 325 330 335

Glu Lys Thr Ile Ser Lys Ala Lys Gly Gin Pro Arg Glu Pro Gin Val 340 345 350

Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gin Val Ser 355 360 365

Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu 370 375 380

Trp Glu Ser Asn Gly Gin Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro 385 390 395 400

Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val 405 410 415

Asp Lys Ser Arg Trp Gin Gin Gly Asn Val Phe Ser Cys Ser Val Met 420 425 430

His Glu Ala Leu His Asn His Tyr Thr Gin Lys Ser Leu Ser Leu Ser 435 440 445

Pro Gly Lys 450 <210> 60 <211> 1353

<212> DNA <213> Homo sapiens <220> <221 > CDS <222> (1) .. (1353) <400> 60 cag gtc cag ctg gtg cag tct ggg get gag gtg aag aag eet ggg tee 48

Gin Val Gin Leu Val Gin Ser Gly Ala Glu Val Lys Lys Pro Gly Ser 15 10 15 teg gtg aaa gtc tct tge aag get tct gga ggc ccc tte ege age tat 96

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Pro Phe Arg Ser Tyr 20 25 30 get ate age tgg gtg ega cag gcc eet gga caa ggg eet gag tgg atg 144

Ala Ile Ser Trp Val Arg Gin Ala Pro Gly Gin Gly Pro Glu Trp Met 35 40 45 gga ggg ate atc eet att ttt ggt aca aca aaa tac gea ccg aag tte 192

Gly Gly Ile Ile Pro Ile Phe Gly Thr Thr Lys Tyr Ala Pro Lys Phe 50 55 60 cag ggc aga gtc aeg att acc gcg gac gat tte gcg ggc aca gtt tae 240

Gin Gly Arg Val Thr Ile Thr Ala Asp Asp Phe Ala Gly Thr Val Tyr 65 70 75 80 atg gag ctg age age ctg ega tct gag gac aeg gcc atg tac tac tgt 288

Ala Lys His Met Gly Tyr Gin Val Arg Glu Thr Met Asp Val Trp Gly 100 105 110 aaa ggg acc aeg gtc acc gtc teg agt get age acc aag ggc ccc age 384

Lys Gly Thr Thr Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser 115 120 125 gtg tte ccc ctg gcc ccc age age aag age acc age ggc ggc aca gcc 432

Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala 130 135 140 gcc ctg ggc tge ctg gtg aag gac tac tte ccc gag ccc gtg acc gtg 480

Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val 145 150 155 160 age tgg aac age ggc gcc ttg acc age ggc gtg cac acc tte ccc gcc 528

Val Leu Gin Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val 180 185 190 ccc age age age ctg ggc acc cag acc tac atc tge aac gtg aac cac 624

Pro Ser Ser Ser Leu Gly Thr Gin Thr Tyr Ile Cys Asn Val Asn His 195 200 205 aag ccc age aac acc aag gtg gac aaa ege gtg gag ccc aag age tge 672

Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser Cys 210 215 220 gac aag acc cac acc tge ccc ccc tge eet gcc ccc gag ctg ctg ggc 720

Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly 225 230 235 240 gga ccc tee gtg tte ctg tte ccc ccc aag ccc aag gac acc etc atg 768

Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met 245 250 255 ate age egg acc ccc gag gtg acc tge gtg gtg gtg gac gtg age cac 816

Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His 260 265 270 gag gac ccc gag gtg aag tte aac tgg tac gtg gac ggc gtg gag gtg 864

His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gin Tyr Asn Ser Thr Tyr 290 295 300 egg gtg gtg age gtg etc acc gtg ctg cac cag gac tgg ctg aac ggc 960

Arg Val Val Ser Val Leu Thr Val Leu His Gin Asp Trp Leu Asn Gly 305 310 315 320 aag gag tac aag tge aag gtg age aac aag gcc ctg eet gcc ccc atc 1008

Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile 325 330 335 gag aag acc atc age aag gcc aag ggc cag ccc egg gag ccc cag gtg 1056

Glu Lys Thr Ile Ser Lys Ala Lys Gly Gin Pro Arg Glu Pro Gin Val 340 345 350 tac acc ctg ccc ccc age egg gag gag atg acc aag aac cag gtg tee 1104

Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gin Val Ser 355 360 365 etc acc tgt ctg gtg aag ggc tte tac ccc age gac ate gcc gtg gag 1152

Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu 370 375 380 tgg gag age aac ggc cag ccc gag aac aac tac aag acc acc ccc eet 1200

Trp Glu Ser Asn Gly Gin Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro 385 390 395 400 gtg ctg gac age gac ggc age tte tte ctg tac age aag etc acc gtg 1248

Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val 405 410 415 gac aag age egg tgg cag cag ggc aac gtg tte age tgc age gtg atg 1296

Asp Lys Ser Arg Trp Gin Gin Gly Asn Val Phe Ser Cys Ser Val Met 420 425 430 cac gag gcc ctg cac aac cac tac acc cag aag age ctg age ctg age 1344

Pro Gly Lys 450 <210>61 <211 > 451

<212> PRT <213> Homo sapiens <400> 61

Gin Val Gin Leu Val Gin Ser Gly Ala Glu Val Lys Lys Pro Gly Ser 15 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Pro Phe Arg Ser Tyr 20 25 30

Ala Ile Ser Trp Val Arg Gin Ala Pro Gly Gin Gly Pro Glu Trp Met 35 40 45

Gly Gly Ile Ile Pro Ile Phe Gly Thr Thr Lys Tyr Ala Pro Lys Phe 50 55 60

Gin Gly Arg Val Thr Ile Thr Ala Asp Asp Phe Ala Gly Thr Val Tyr 65 70 75 80

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Met Tyr Tyr Cys 85 90 95

Ala Lys His Met Gly Tyr Gin Val Arg Glu Thr Met Asp Val Trp Gly 100 105 110

Lys Gly Thr Thr Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser 115 120 125

Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala 130 135 140

Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val 145 150 155 160

Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala 165 170 175

Val Leu Gin Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val 180 185 190

Pro Ser Ser Ser Leu Gly Thr Gin Thr Tyr Ile Cys Asn Val Asn His 195 200 205

Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser Cys 210 215 220

Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly 225 230 235 240

Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met 245 250 255

Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His 260 265 270

Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val 275 280 285

His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gin Tyr Asn Ser Thr Tyr 290 295 300

Arg Val Val Ser Val Leu Thr Val Leu His Gin Asp Trp Leu Asn Gly 305 310 315 320

Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile 325 330 335

Glu Lys Thr Ile Ser Lys Ala Lys Gly Gin Pro Arg Glu Pro Gin Val 340 345 350

Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gin Val Ser 355 360 365

Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu 370 375 380

Trp Glu Ser Asn Gly Gin Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro 385 390 395 400

Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val 405 410 415

Asp Lys Ser Arg Trp Gin Gin Gly Asn Val Phe Ser Cys Ser Val Met 420 425 430

His Glu Ala Leu His Asn His Tyr Thr Gin Lys Ser Leu Ser Leu Ser 435 440 445

Pro Gly Lys 450 <210> 62 <211> 1353

<212> DNA <213> Homo sapiens <220>

<221 > CDS <222> (1)..(1353) <400> 62 gag gtg cag ctg gtg gag tct ggg get gag gtg aag aag eet ggg tee 48

Glu Val Gin Leu Val Glu Ser Gly Ala Glu Val Lys Lys Pro Gly Ser 15 10 15 teg gtg aaa gtc tct tgc aag get tct gga ggc ccc tte ege age tat 96

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Pro Phe Arg Ser Tyr 20 25 30 get ate age tgg gtg ega cag gce eet gga caa ggg eet gag tgg atg 144

Gly Gly Ile Ile Pro Ile Phe Gly Thr Thr Lys Tyr Ala Pro Lys Phe 50 55 60 cag ggc aga gtc aeg att acc gcg gac gat tte gcg ggc aca gtt tac 240

Gin Gly Arg Val Thr Ile Thr Ala Asp Asp Phe Ala Gly Thr Val Tyr 65 70 75 80 atg gag ctg age age ctg ega tct gag gac aeg gce atg tac tac tgt 288

Lys Gly Thr Thr Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser 115 120 125 gtg tte ccc ctg gee ccc age age aag age acc age ggc ggc aca gce 432

Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala 130 135 140 gce ctg ggc tgc ctg gtg aag gac tac tte ccc gag ccc gtg acc gtg 480

Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val 145 150 155 160 age tgg aac age ggc gce ttg acc age ggc gtg cac acc tte ccc gce 528

Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser Cys 210 215 220 gac aag acc cac acc tgc ccc ccc tgc eet gce ccc gag ctg ctg ggc 720

Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val 275 280 285 cac aac gce aag acc aag ccc egg gag gag cag tac aac age acc tac 912

Arg Val Val Ser Val Leu Thr Val Leu His Gin Asp Trp Leu Asn Gly 305 310 315 320 aag gag tac aag tgc aag gtg age aac aag gce ctg eet gce ccc atc 1008

Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile 325 330 335 gag aag acc ate age aag gce aag ggc cag ccc egg gag ccc cag gtg 1056

Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gin Val Ser 355 360 365 etc acc tgt ctg gtg aag ggc tte tac ccc age gac ate gce gtg gag 1152

Pro Gly Lys 450 <210> 63 <211 > 451

<212> PRT <213> Homo sapiens <400> 63

Glu Val Gin Leu Val Glu Ser Gly Ala Glu Val Lys Lys Pro Gly Ser 15 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Pro Phe Arg Ser Tyr 20 25 30

Ala Ile Ser Trp Val Arg Gin Ala Pro Gly Gin Gly Pro Glu Trp Met 35 40 45

Gly Gly Ile Ile Pro Ile Phe Gly Thr Thr Lys Tyr Ala Pro Lys Phe 50 55 60

Gin Gly Arg Val Thr Ile Thr Ala Asp Asp Phe Ala Gly Thr Val Tyr 65 70 75 80

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Met Tyr Tyr Cys 85 90 95

Ala Lys His Met Gly Tyr Gin Val Arg Glu Thr Met Asp Val Trp Gly 100 105 110

Lys Gly Thr Thr Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser 115 120 125

Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala 130 135 140

Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val 145 150 155 160

Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala 165 170 175

Val Leu Gin Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val 180 185 190

Pro Ser Ser Ser Leu Gly Thr Gin Thr Tyr lie Cys Asn Val Asn His 195 200 205

Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser Cys 210 215 220

Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly 225 230 235 240

Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met 245 250 255 lie Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His 260 265 270

Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val 275 280 285

His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gin Tyr Asn Ser Thr Tyr 290 295 300

Arg Val Val Ser Val Leu Thr Val Leu His Gin Asp Trp Leu Asn Gly 305 310 315 320

Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro lie 325 330 335

Glu Lys Thr lie Ser Lys Ala Lys Gly Gin Pro Arg Glu Pro Gin Val 340 345 350

Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gin Val Ser 355 360 365

Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp lie Ala Val Glu 370 375 380

Trp Glu Ser Asn Gly Gin Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro 385 390 395 400

Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val 405 410 415

Asp Lys Ser Arg Trp Gin Gin Gly Asn Val Phe Ser Cys Ser Val Met 420 425 430

His Glu Ala Leu His Asn His Tyr Thr Gin Lys Ser Leu Ser Leu Ser 435 440 445

Pro Gly Lys 450 <210> 64 <211> 1353

<212> DNA <213> Homo sapiens <220> <221 > CDS <222> (1)..(1353) <400> 64 gag gtg cag ctg gtg gag tct ggg get gag gtg aag aag cct ggg tee 48

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Pro Phe Arg Ser Tyr 20 25 30 get ate age tgg gtg ega cag gee cct gga caa ggg cct gag tgg atg 144

Ala Ile Ser Trp Val Arg Gin Ala Pro Gly Gin Gly Pro Glu Trp Met 35 40 45 gga ggg ate ate cct att ttt ggt aca aca aaa tac gca ccg aag ttc 192

Gly Gly lie lie Pro lie Phe Gly Thr Thr Lys Tyr Ala Pro Lys Phe 50 55 60 cag ggc aga gtc aeg att acc geg gac gat ttc geg ggc aca gtt tac 240

Gin Gly Arg Val Thr lie Thr Ala Asp Asp Phe Ala Gly Thr Val Tyr 65 70 75 80 atg gag ctg age age ctg ega tct gag gac aeg gee atg tac tac tgt 288

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Met Tyr Tyr Cys 85 90 95 geg aaa cat atg ggg tac cag gtg ege gaa act atg gac gtc tgg ggc 336

Lys Gly Thr Thr Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser 115 120 125 gtg ttc ccc ctg gee ccc age age aag age acc age ggc ggc aca gee 432

Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala 130 135 140 gee ctg ggc tgc ctg gtg aag gac tac ttc ccc gag ccc gtg acc gtg 480

Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val 145 150 155 160 age tgg aac age ggc gee ttg ace age ggc gtg cac acc ttc ccc gee 528

Val Leu Gin Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val 180 185 190 ccc age age age ctg ggc acc cag acc tac ate tgc aac gtg aac cac 624

Pro Ser Ser Ser Leu Gly Thr Gin Thr Tyr lie Cys Asn Val Asn His 195 200 205 aag ccc age aac acc aag gtg gac aaa ege gtg gag ccc aag age tgc 672

Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser Cys 210 215 220 gac aag acc cac acc tgc ccc ccc tgc cct gee ccc gag ctg ctg ggc 720

Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met 245 250 255 ate age egg acc ccc gag gtg acc tgc gtg gtg gtg gac gtg age cac 816 lie Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His 260 265 270 gag gac ccc gag gtg aag ttc aac tgg tac gtg gac ggc gtg gag gtg 864

Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val 275 280 285 cac aac gee aag acc aag ccc egg gag gag cag tac aac age acc tac 912

Arg Val Val Ser Val Leu Thr Val Leu His Gin Asp Trp Leu Asn Gly 305 310 315 320 aag gag tac aag tgc aag gtg age aac aag gee ctg cct gee ccc ate 1008

Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro lie 325 330 335 gag aag acc ate age aag gee aag ggc cag ccc egg gag ccc cag gtg 1056

Glu Lys Thr lie Ser Lys Ala Lys Gly Gin Pro Arg Glu Pro Gin Val 340 345 350 tac acc ctg ccc ccc age egg gag gag atg acc aag aac cag gtg tee 1104

Pro Gly Lys 450 <210> 65 <211 > 451

<212> PRT <213> Homo sapiens <400> 65

Glu Val Gin Leu Val Glu Ser Gly Ala Glu Val Lys Lys Pro Gly Ser 15 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Pro Phe Arg Ser Tyr 20 25 30

Ala Ile Ser Trp Val Arg Gin Ala Pro Gly Gin Gly Pro Glu Trp Met. 35 40 45

Gly Gly Ile Ile Pro Ile Phe Gly Thr Thr Lys Tyr Ala Pro Lys Phe 50 55 €0

Gin Gly Arg Val Thr Ile Thr Ala Asp Asp Phe Ala Gly Thr Val Tyr 65 70 75 80

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Met Tyr Tyr Cys 85 90 95

Ala Lys His Met Gly Tyr Gin Val Arg Glu Thr Met Asp Val Trp Gly 100 105 110

Lys Gly Thr Thr Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser 115 120 125

Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala 130 135 140

Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val 145 150 155 160

Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala 165 170 175

Val Lou Gin Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val 180 185 190

Pro Ser Ser Ser Leu Gly Thr Gin Thr Tyr Ile Cys Asn Val Asn His 195 200 205

Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser Cys 210 215 220

Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly 225 230 235 240

Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met 245 250 255

Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His 260 265 270

Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val 275 280 285

His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gin Tyr Asn Ser Thr Tyr 290 295 300

Arg Val Val Ser Val Leu Thr Val Leu His Gin Asp Trp Leu Asn Gly 305 310 315 320

Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile 325 330 335

Glu Lys Thr Ile Ser Lys Ala Lys Gly Gin Pro Arg Glu Pro Gin Val 340 345 350

Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gin Val Ser 355 360 365

Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu 370 375 380

Trp Glu Ser Asn Gly Gin Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro 385 390 395 400

Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val 405 410 415

Asp Lys Ser Arg Trp Gin Gin Gly Asn Val Phe Ser Cys Ser Val Met 420 425 430

His Glu Ala Leu His Asn His Tyr Thr Gin Lys Ser Leu Ser Leu Ser 435 440 445

Pro Gly Lys 450 <210> 66 <211 > 1350

<212> DNA <213> Homo sapiens <220> <221 > CDS <222> (1)..(1350) <400> 66 cag gta cag ctg cag cag tea ggg get gag gtg aag aag cct ggg tee 48

Gin Val Gin Leu Gin Gin Ser Gly Ala Glu Val Lys Lys Pro Gly Ser 15 10 15 teg gtg aag gtc tee tgc aag gtt tee gga gtc att tte age ggc agt 96

Ser Val Lys Val Ser Cys Lys Val Ser Gly Val lie Phe Ser Gly Ser 20 25 30 geg ate age tgg gtg ega cag gee cct gga caa ggc ett gag tgg atg 144

Ala Ile Ser Trp Val Arg Gin Ala Pro Gly Gin Gly Leu Glu Trp Met 35 40 45 gga ggg ate age cct etc ttt ggc aca aca aat tac gca caa aag ttc 192

Gly Gly lie Ser Pro Leu Phe Gly Thr Thr Asn Tyr Ala Gin Lys Phe 50 55 60 cag ggc aga gtc aeg att acc geg gac caa tee aeg aac aca ace tac 240

Gin Gly Arg Val Thr lie Thr Ala Asp Gin Ser Thr Asn Thr Thr Tyr 65 70 75 80 atg gag gtg aac age ctg aga tat gag gac aeg gee gtg tat ttc tgt 288

Met Glu Val Asn Ser Leu Arg Tyr Glu Asp Thr Ala Val Tyr Phe Cys 85 90 95 geg ega ggt cca aaa tat tac agt gag tac atg gac gtc tgg ggc aaa 336

Ala Arg Gly Pro Lys Tyr Tyr Ser Glu Tyr Met Asp Val Trp Gly Lys 100 105 110 ggg ace aeg gtc acc gtc teg agt get age acc aag ggc ccc age gtg 384

Gly Thr Thr Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val 115 120 125 ttc ccc ctg gee ccc age age aag age acc age ggc ggc aca gee gee 432

Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala 130 135 140 ctg ggc tgc ctg gtg aag gac tac ttc ccc gag ccc gtg acc gtg age 480

Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser 145 150 155 160 tgg aac age ggc gee ttg acc age ggc gtg cac acc ttc ccc gee gtg 528

Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val 165 170 175 ctg cag age age ggc ctg tac age ctg age age gtg gtg acc gtg ccc 576

Leu Gin Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro 180 185 190 age age age ctg ggc ace cag ace tac ate tgc aac gtg aac cac aag 624

Ser Ser Ser Leu Gly Thr Gin Thr Tyr Ile Cys Asn Val Asn His Lys 195 200 205 ccc age aac acc aag gtg gac aaa ege gtg gag ccc aag age tgc gac 672

Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser Cys Asp 210 215 220 aag acc cac acc tgc ccc ccc tgc cct gee eee gag ctg ctg ggc gga 720

Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly 225 230 235 240 ccc tec gtg ttc ctg ttc ccc ccc aag ccc aag gac acc etc atg ate 768

Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met lie 245 250 255 age egg acc ccc gag gtg acc tgc gtg gtg gtg gac gtg age cac gag 816

Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu 260 265 270 gac ccc gag gtg aag ttc aac tgg tac gtg gac ggc gtg gag gtg cac 864

Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His 275 280 285 aac gee aag acc aag ccc egg gag gag cag tac aac age acc tac egg 912

Asn Ala Lys Thr Lys Pro Arg Glu Glu Gin Tyr Asn Ser Thr Tyr Arg 290 295 300 gtg gtg age gtg etc acc gtg ctg cac cag gac tgg ctg aac ggc aag 960

Val Val Ser Val Leu Thr Val Leu His Gin Asp Trp Leu Asn Gly Lys 305 310 315 320 gag tac aag tgc aag gtg age aac aag gee ctg cct gee ccc ate gag 1008

Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro lie Glu 325 330 335 aag acc ate age aag gee aag ggc cag ccc egg gag ccc cag gtg tac 1056

Lys Thr lie Ser Lys Ala Lys Gly Gin Pro Arg Glu Pro Gin Val Tyr 340 345 350 acc ctg ccc ccc age egg gag gag atg acc aag aac cag gtg tee etc 1104

Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gin Val Ser Leu 355 360 365 acc tgt ctg gtg aag ggc ttc tac ccc age gac ate gee gtg gag tgg 1152

Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp lie Ala Val Glu Trp 370 375 380 gag age aac ggc cag ccc gag aac aac tac aag acc acc ccc cct gtg 1200

Glu Ser Asn Gly Gin Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val 385 390 395 400 ctg gac age gac ggc age ttc ttc ctg tac age aag etc acc gtg gac 1248

Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp 405 410 415 aag age egg tgg cag cag ggc aac gtg ttc age tgc age gtg atg cac 1296

Lys Ser Arg Trp Gin Gin Gly Asn Val Phe Ser Cys Ser Val Met His 420 425 430 gag gee ctg cac aac cac tac acc cag aag age ctg age ctg age ccc 1344

Glu Ala Leu His Asn His Tyr Thr Gin Lys Ser Leu Ser Leu Ser Pro 435 440 445 ggc aag 1350

Gly Lys 450 <210> 67 <211 >450

<212> PRT <213> Homo sapiens <400> 67

Gin Val Gin Leu Gin Gin Ser Gly Ala Glu Val Lys Lys Pro Gly Ser 15 10 15

Ser Val Lys Val Ser Cys Lys Val Ser Gly Val lie Phe Ser Gly Ser 20 25 30

Ala Ile Ser Trp Val Arg Gin Ala Pro Gly Gin Gly Leu Glu Trp Met 35 40 45

Gly Gly lie Ser Pro Leu Phe Gly Thr Thr Asn Tyr Ala Gin Lys Phe 50 55 60

Gin Gly Arg Val Thr lie Thr Ala Asp Gin Ser Thr Asn Thr Thr Tyr 65 70 75 80

Met Glu Val Asn Ser Leu Arg Tyr Glu Asp Thr Ala Val Tyr Phe Cys 85 90 95

Ala Arg Gly Pro Lys Tyr Tyr Ser Glu Tyr Met Asp Val Trp Gly Lys 100 105 110

Gly Thr Thr Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val 115 120 125

Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala 130 135 140

Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser 145 150 155 160

Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val 165 170 175

Leu Gin Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro 180 185 190

Ser Ser Ser Leu Gly Thr Gin Thr Tyr lie Cys Asn Val Asn His Lys 195 200 205

Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser Cys Asp 210 215 220

Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly 225 230 235 240

Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Het Ile 245 250 255

Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu 260 265 270

Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His 275 280 285

Asn Ala Lys Thr Lys Pro Arg Glu Glu Gin Tyr Asn Ser Thr Tyr Arg 290 295 300

Val Val Ser Val Leu Thr Val Leu His Gin Asp Trp Leu Asn Gly Lys 305 310 315 320

Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu 325 330 335

Lys Thr Ile Ser Lys Ala Lys Gly Gin Pro Arg Glu Pro Gin Val Tyr 340 345 350

Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gin Val Ser Leu 355 360 365

Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp 370 375 380

Glu Ser Asn Gly Gin Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val 385 390 395 400

Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp 405 410 415

Lys Ser Arg Trp Gin Gin Gly Asn Val Phe Ser Cys Ser Val Met His 420 425 430

Glu Ala Leu His Asn His Tyr Thr Gin Lys Ser Leu Ser Leu Ser Pro 435 440 445

Gly Lys 450 <210> 68 <211 > 1350

<212> DNA <213> Homo sapiens <220> <221 > CDS <222> (1)..(1350) <400> 68 cag gtc cag ctg gta cag tct ggg get gag gtg aag aag cct ggg tee 48

Gin Val Gin Leu Val Gin Ser Gly Ala Glu Val Lys Lys Pro Gly Ser 15 10 15 teg gtg aag gtc tee tgc aag get tct gga ggc ace tte agt agt tat 96

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Ser Ser Tyr 20 25 30 get ate age tgg gtg ega cag gee cct gga caa ggg ett gag tgg atg 144

Ala Ile Ser Trp Val Arg Gin Ala Pro Gly Gin Gly Leu Glu Trp Met 35 40 45 gga gga ate atg ggt atg ttt ggc aca act aac tac gca cag aag ttc 192

Gly Gly lie Met Gly Met Phe Gly Thr Thr Asn Tyr Ala Gin Lys Phe 50 55 60 cag ggc aga gtc aeg att acc geg gac gaa ttc aeg age gca gee tac 240

Gin Gly Arg Val Thr lie Thr Ala Asp Glu Phe Thr Ser Ala Ala Tyr 65 70 75 80 atg gag ctg agg age ctg aga tct gag gac aeg gee gtc tac tac tgt 288

Met Glu Leu Arg Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 geg agg tct agt ggt tat tac ccc gaa tac ttc cag gac tgg ggc cag 336

Ala Arg Ser Ser Gly Tyr Tyr Pro Glu Tyr Phe Gin Asp Trp Gly Gin 100 105 110 ggc acc ctg gtc acc gtc teg agt get age acc aag ggc ccc age gtg 384

Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val 115 120 125 ttc ccc ctg gee ccc age age aag age acc age ggc ggc aca gee gee 432

Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val 165 170 175 ctg cag age age ggc ctg tac age ctg age age gtg gtg acc gtg ccc 57 6

Leu Gin Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro 180 185 190 age age age ctg ggc acc cag acc tac ate tgc aac gtg aac cac aag 624

Ser Ser Ser Leu Gly Thr Gin Thr Tyr lie Cys Asn Val Asn His Lys 195 200 205 ccc age aac acc aag gtg gac aaa ege gtg gag ccc aag age tgc gac 672

Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser Cys Asp 210 215 220 aag acc cac acc tgc ccc ccc tgc cct gcc ccc gag ctg ctg ggc gga 720

Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly 225 230 235 240 ccc tcc gtg ttc ctg ttc ccc ccc aag ccc aag gac acc ctc atg atc 768

Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile 245 250 255 age egg acc ccc gag gtg acc tgc gtg gtg gtg gac gtg age cac gag 816

Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His 275 280 285 aac gcc aag acc aag ccc egg gag gag cag tac aac age acc tac egg 912

Val Val Ser Val Leu Thr Val Leu His Gin Asp Trp Leu Asn Gly Lys 305 310 315 320 gag tac aag tgc aag gtg age aac aag gcc ctg cct gcc ccc atc gag 1008

Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu 325 330 335 aag acc atc age aag gcc aag ggc cag ccc egg gag ccc cag gtg tac 1056

Lys Thr Ile Ser Lys Ala Lys Gly Gin Pro Arg Glu Pro Gin Val Tyr 340 345 350 acc ctg ccc ccc age egg gag gag atg acc aag aac cag gtg tee etc 1104

Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gin Val Ser Leu 355 360 365 acc tgt ctg gtg aag ggc ttc tac ccc age gac atc gcc gtg gag tgg 1152

Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp 370 375 380 gag age aac ggc cag ccc gag aac aac tac aag acc acc ccc cct gtg 1200

Lys Ser Arg Trp Gin Gin Gly Asn Val Phe Ser Cys Ser Val Met His 420 425 430 gag gcc ctg cac aac cac tac acc cag aag age ctg age ctg age ccc 1344

Gly Lys 450 <210> 69 <211 >450

<212> PRT <213> Homo sapiens <400> 69

Gin Val Gin Leu Val Gin Ser Gly Ala Glu Val Lys Lys Pro Gly Ser IS 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Ser Ser Tyr 20 25 30

Ala ile Ser Trp Val Arg Gin Ala Pro Gly Gin Gly Leu Glu Trp Met 35 40 45

Gly Gly lie Met Gly Met Phe Gly Thr Thr Asn Tyr Ala Gin Lys Phe 50 55 €0

Gin Gly Arg Val Thr lie Thr Ala Asp Glu Phe Thr Ser Ala Ala Tyr 65 70 75 80

Met Glu Leu Arg Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95

Ala Arg Ser Ser Gly Tyr Tyr Pro Glu Tyr Phe Gin Asp Trp Gly Gin 100 105 110

Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val 115 120 125

Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala 130 135 140

Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser 145 150 155 160

Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val 165 170 175

Leu Gin Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro 180 185 190

Ser Ser Ser Leu Gly Thr Gin Thr Tyr lie Cys Asn Val Asn His Lys 195 200 205

Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser Cys Asp 210 215 220

Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly 225 230 235 240

Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met lie 245 250 255

Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu 260 265 270

Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His 275 280 285

Asn Ala Lys Thr Lys Pro Arg Glu Glu Gin Tyr Asn Ser Thr Tyr Arg 290 295 300

Val Val Ser Val Leu Thr Val Leu His Gin Asp Trp Leu Asn Gly Lys 305 310 315 320

Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu 325 330 335

Lys Thr Ile Ser Lys Ala Lys Gly Gin Pro Arg Glu Pro Gin Val Tyr 340 345 350

Thr Leu Pro Pro Ser Arg Glu Glu Mel: Thr Lys Asn Gin Val Ser Leu 355 360 365

Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp 370 375 380

Glu Ser Asn Gly Gin Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val 385 390 395 400

Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp 405 410 415

Lys Ser Arg Trp Gin Gin Gly Asn Val Phe Ser Cys Ser Val Met His 420 425 430

Glu Ala Leu His Asn His Tyr Thr Gin Lys Ser Leu Ser Leu Ser Pro 435 440 445

Gly Lys 450 <210> 70 <211> 1356

<212> DNA <213> Homo sapiens <220> <221 > CDS <222> (1)..(1356) <400> 70 cag gtc cag ctg gtg cag tct ggg gga ggc ctg gtc aag cct ggg ggg 48

Gin Val Gin Leu Val Gin Ser Gly Gly Gly Leu Val Lys Pro Gly Gly 15 10 15 tcc ctg aga ctc tcc tgt gca gcc tct gga ttc acc ttc agt age tat 96

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Ser Tyr 20 25 30 age atg aac tgg gtc ege cag get cca ggg aag ggg ctg gag tgg gtc 144

Ser Met Asn Trp Val Arg Gin Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45 tea tcc att agt agt agt agt agt tac ata tac tac gta gac tea gtg 192

Ser Ser Ile Ser Ser Ser Ser Ser Tyr Ile Tyr Tyr Val Asp Ser Val 50 55 60 aag ggc ega ttc acc ate tcc aga gac aac gcc aag aac tea ctg tat 240

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Ser Leu Tyr 65 70 75 80 ctg caa atg aac age ctg aga gcc gag gac aeg get gtg tat tac tgt 288

Leu Gin Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 gcg aga ggt ggt ggg age tac ggg gcc tac gaa ggc ttt gac tac tgg 336

Ala Arg Gly Gly Gly Ser Tyr Gly Ala Tyr Glu Gly Phe Asp Tyr Trp 100 105 110 ggc cag ggc acc ctg gtc acc gtc teg agt get age acc aag ggc ccc 384

Gly Gin Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro 115 120 125 age gtg ttc ccc ctg gcc ccc age age aag age acc age ggc ggc aca 432

Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr 130 135 140 gcc gcc ctg ggc tgc ctg gtg aag gac tac ttc ccc gag ccc gtg acc 480

Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr 145 150 155 160 gtg age tgg aac age ggc gcc ttg acc age ggc gtg cac acc ttc ccc 528

Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro 165 170 175 gcc gtg ctg cag age age ggc ctg tac age ctg age age gtg gtg acc 576

Ala Val Leu Gin Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr 160 185 190 gtg ccc age age age ctg ggc acc cag acc tac atc tgc aac gtg aac 624

Val Pro Ser Ser Ser Leu Gly Thr Gin Thr Tyr Ile Cys Asn Val Asn 195 200 205 cac aag ccc age aac acc aag gtg gac aaa cgc gtg gag ccc aag age 672

His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser 210 215 220 tgc gac aag acc cac acc tgc ccc ccc tgc cct gcc ccc gag ctg ctg 720

Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu 225 230 235 240 ggc gga ccc tcc gtg ttc ctg ttc ccc ccc aag ccc aag gac acc ctc 768

Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu 245 250 255 atg atc age egg acc ccc gag gtg acc tgc gtg gtg gtg gac gtg age 816

Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser 260 265 270 cac gag gac ccc gag gtg aag ttc aac tgg tac gtg gac ggc gtg gag 864

His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu 275 280 285 gtg cac aac gcc aag acc aag ccc cgg gag gag cag tac aac age acc 912

Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gin Tyr Asn Ser Thr 290 295 300 tac cgg gtg gtg age gtg ctc acc gtg ctg cac cag gac tgg ctg aac 960

Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gin Asp Trp Leu Asn 305 310 315 320 ggc aag gag tac aag tgc aag gtg age aac aag gcc ctg cct gcc ccc 1008

Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro 325 330 335 atc gag aag acc atc age aag gcc aag ggc cag ccc cgg gag ccc cag 1056

Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gin Pro Arg Glu Pro Gin 340 345 350 gtg tac acc ctg ccc ccc age cgg gag gag atg acc aag aac cag gtg 1104

Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gin Val 355 360 365 tee ctc acc tgt ctg gtg aag ggc ttc tac ccc age gac atc gcc gtg 1152

Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val 370 375 380 gag tgg gag age aac ggc cag ccc gag aac aac tac aag acc acc ccc 1200

Glu Trp Glu Ser Asn Gly Gin Pro Glu Asn Asn Tyr Lys Thr Thr Pro 385 390 395 400 cct gtg ctg gac age gac ggc age ttc ttc ctg tac age aag ctc acc 1248

Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr 405 410 415 gtg gac aag age cgg tgg cag cag ggc aac gtg ttc age tgc age gtg 1296

Val Asp Lys Ser Arg Trp Gin Gin Gly Asn Val Phe Ser Cys Ser Val 420 425 430 atg cac gag gcc ctg cac aac cac tac acc cag aag age ctg age ctg 1344

Met His Glu Ala Leu His Asn His Tyr Thr Gin Lys Ser Leu Ser Leu 435 440 445 age ccc ggc aag 1356

Ser Pro Gly Lys 450 <210>71 <211 >452

<212> PRT <213> Homo sapiens <400> 71

Gin Val Gin Leu Val Gin Ser Gly Gly Gly Léu Val Lys Pro Gly Gly 15 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Ser Tyr 20 25 30

Ser Met Asn Trp Val Arg Gin Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45

Ser Ser Ile Ser Ser Ser Ser Ser Tyr Ile Tyr Tyr Val Asp Ser Val 50 55 60

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Ser Leu Tyr 65 70 75 80

Leu Gin Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95

Ala Arg Gly Gly Gly Ser Tyr Gly Ala Tyr Glu Gly Phe Asp Tyr Trp 100 105 110

Gly Gin Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro 115 120 125

Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr 130 135 140

Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr 145 150 155 160

Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val Kis Thr Phe Pro 165 170 175

Ala Val Leu Gin Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr 180 185 190

Val Pro Ser Ser Ser Leu Gly Thr Gin Thr Tyr Ile Cys Asn Val Asn 195 200 205

Kis Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser 210 215 220

Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu 225 230 235 240

Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu 245 250 255

Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser 260 265 270

His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu 275 280 285

Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gin Tyr Asn Ser Thr 290 295 300

Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gin Asp Trp Leu Asn 305 310 315 320

Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro 325 330 335

Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gin Pro Arg Glu Pro Gin 340 345 350

Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gin Val 355 360 365

Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val 370 375 3S0

Glu Trp Glu Ser Asn Gly Gin Pro Glu Asn Asn Tyr Lys Thr Thr Pro 385 390 395 400

Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr 405 410 415

Val Asp Lys Ser Arg Trp Gin Gin Gly Asn Val Phe Ser Cys Ser Val 420 425 430

Met His Glu Ala Leu His Asn His Tyr Thr Gin Lys Ser Leu Ser Leu 435 440 445

Ser Pro Gly Lys 450 <210> 72 <211> 1353

<212> DNA <213> Homo sapiens <220> <221 > CDS <222> (1)..(1353) <400> 72 gag gtg eag ctg gtg gag tct ggg get gag gtg aag aag eet ggg tec 48

Glu Val Gin Leu Val Glu Ser Gly Ala Glu Val Lys Lys Pro Gly Ser 15 10 15 teg gtg aaa gtc tot tgc aag get tct gga ggc cec tte ege age tat 96

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Pro Phe Arg Ser Tyr 20 25 30 get ate age tgg gtg ega eag gec eet gga caa ggg eet gag tgg atg 144

Pro Ser Ser Ser Leu Gly Thr Gin Thr Tyr Ile Cys Asn Val Asn His 195 200 205 aag ccc age aac acc aag gtg gac aaa cgc gtg gag ccc aag age tgc 672

Asp Lys Thr His Thr Cys Fro Pro Cys Pro Ala Pro Glu Leu Leu Gly 225 230 235 240 gga ccc tee gtg ttc ctg ttc ccc ccc aag ccc aag gac acc etc atg 768

Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met 245 250 255 atc age egg acc ccc gag gtg acc tgc gtg gtg gtg gac gtg age cac 816

Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro lie 325 330 335 gag aag ace ate age aag gee aag ggc eag ccc egg gag ccc cag gtg 1056

Glu Lys Thr Ile Ser Lys Ala Lys Gly Gin Pro Arg Glu Pro Gin Val 340 345 350 tac acc ctg ccc ccc age egg gag gag atg acc aag aac cag gtg tcc 1104

Pro Gly Lys 450 <210> 73 <211 > 451

<212> PRT <213> Homo sapiens <400> 73

Glu Val Gin Leu Val Glu Ser Gly Ala Glu Val Lys Lys Pro Gly Ser 15 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Pro Phe Arg Ser Tyr 20 25 30

Ala lie Ser Trp Val Arg Gin Ala Pro Gly Gin Gly Pro Glu Trp Met 35 40 45

Gly Gly lie lie Pro lie Phe Gly Thr Thr Lys Tyr Ala Pro Lys Phe 50 55 60

Gin Gly Arg Val Thr Ile Thr Ala Asp Asp Phe Ala Gly Thr Val Tyr 65 70 75 80

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Met Tyr Tyr Cys 85 90 95

Ala Lys His Met Gly Tyr Gin Val Arg Glu Thr Met Asp Val Trp Gly 100 105 110

Lys Gly Thr Thr Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser 115 120 125

Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala 130 135 140

Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val 145 150 155 160

Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala 165 170 175

Val Leu Gin Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val 180 185 190

Pro Ser Ser Ser Leu Gly Thr Gin Thr Tyr lie Cys Asn Val Asn His 195 200 205

Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser Cys 210 215 220

Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly 225 230 235 240

Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val 275 280 285

His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gin Tyr Asn Ser Thr Tyr 290 295 300

Arg Val Val Ser Val Leu Thr Val Leu His Gin Asp Trp Leu Asn Gly 305 310 315 320

Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro He 325 330 335

Glu Lys Thr lie Ser Lys Ala Lys Gly Gin Pro Arg Glu Pro Gin Val 340 345 350

Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gin Val Ser 355 360 365

Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp lie Ala Val Glu 370 375 380

Trp Glu Ser Asn Gly Gin Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro 385 390 395 400

Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val 405 410 415

Asp Lys Ser Arg Trp Gin Gin Gly Asn Val Phe Ser Cys Ser Val Met 420 425 430

His Glu Ala Leu His Asn His Tyr Thr Gin Lys Ser Leu Ser Leu Ser 435 440 445

Pro Gly Lys 450 <210> 74 <211> 1353

<212> DNA <213> Homo sapiens <220> <221 > CDS <222> (1)..(1353) <400> 74 gag gtg cag ctg gtg gag tot ggg get gag gtg aag aag eet ggg tce 48

Glu Val Gin Leu Val Glu Ser Gly Ala Glu Val Lys Lys Pro Gly Ser 15 10 15 teg gtg aaa gtc tet tgc aag get tet gga ggc ccc tte ege age tat 96

Gin Gly Arg Val Thr Ile Thr Ala Asp Asp Phe Ala Gly Thr Val Tyr 65 70 75 80 atg gag ctg age age ctg ega tet gag gac aeg gcc atg tac tac tgt 288

Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala 130 135 140 gcc ctg ggc tgc ctg gtg aag gac tac tte ccc gag ccc gtg acc gtg 480

Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser Cys 210 215 220 gac aag acc cac acc tgc ccc ccc tgc eet gcc ccc gag ctg ctg ggc 720

Arg Val Val Ser Val Leu Thr Val Leu His Gin Asp Trp Leu Asn Gly 305 310 315 320 aag gag tac aag tgc aag gtg age aac aag gcc ctg eet gcc ccc atc 1008

Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile 325 330 335 gag aag acc ate age aag gee aag ggc cag ecc egg gag ccc cag gtg 1056

Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp lie Ala Val Glu 370 375 380 tgg gag age aae ggc cag ccc gag aac aac tae aag acc acc ccc cct 1200

Pro Gly Lys 450 <210> 75 <211 > 451

<212> PRT <213> Homo sapiens <400> 75

Glu Val Gin Leu Val Glu Ser Gly Ala Glu Val Lys Lys Pro Gly Ser 15 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Pro Phe Arg Ser Tyr 20 25 30

Ala lie Ser Trp Val Arg Gin Ala Pro Gly Gin Gly Pro Glu Trp Met 35 40 45

Gly Gly lie lie Pro lie Phe Gly Thr Thr Lys Tyr Ala Pro Lys Phe 50 55 60

Gin Gly Arg Val Thr lie Thr Ala Asp Asp Phe Ala Gly Thr Val Tyr 65 70 75 80

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Met Tyr Tyr Cys 85 90 95

Ala Lys His Met Gly Tyr Gin Val Arg Glu Thr Met Asp Val Trp Gly 100 105 110

Lys Gly Thr Thr Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser 115 120 125

Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala 130 135 140

Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val 145 150 155 160

Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala 165 170 175

Val Leu Gin Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val 180 185 190

Pro Ser Ser Ser Leu Gly Thr Gin Thr Tyr Ile Cys Asn Val Asn His 195 200 205

Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser Cys 210 215 220

Asp Lys Thr Kis Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly 225 230 235 240

Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met 245 250 255

Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His 260 265 270

Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val 275 280 285

His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gin Tyr Asn Ser Thr Tyr 290 295 300

Arg Val Val Ser Val Leu Thr Val Leu His Gin Asp Trp Leu Asn Gly 305 310 315 320

Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile 325 330 335

Glu Lys Thr Ile Ser Lys Ala Lys Gly Gin Pro Arg Glu Pro Gin Val 340 345 350

Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gin Val Ser 355 360 365

Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu 370 375 380

Trp Glu Ser Asn Gly Gin Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro 385 390 395 400

Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val 405 410 415

Asp Lys Ser Arg Trp Gin Gin Gly Asn Val Phe Ser Cys Ser Val Met 420 425 430

His Glu Ala Leu His Asn His Tyr Thr Gin Lys Ser Leu Ser Leu Ser 435 440 445

Pro Gly Lys 450 <210> 76 <211 > 1350

<212> DNA <213> Homo sapiens <220> <221 > CDS <222> (1)..(1350) <400> 76 gag gtg cag ctg gtg gag tct ggg get gag gtg aag aag cca ggg tee 48

Glu Val Gin Leu Val Glu Ser Gly Ala Glu Val Lys Lys Pro Gly Ser 15 10 15 teg gtg aag gtc tee tgt aag gcc tct gga ggc acc tte tee age tat 96

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Ser Ser Tyr 20 25 30 ggt atc age tgg gtg ega cag gcc eet gga eaa ggg ett gag tgg atg 144

Gly Ile Ser Trp Val Arg Gin Ala Pro Gly Gin Gly Leu Glu Trp Met 35 40 45 gga gac ate ate ggt atg ttt ggt tea aca aac tac gea cag aac tte 192

Gly Asp Ile Ile Gly Met Phe Gly Ser Thr Asn Tyr Ala Gin Asn Phe 50 55 60 cag ggc aga etc aeg att acc gcg gac gaa tee aeg age aca gcc tac 240

Gin Gly Arg Leu Thr Ile Thr Ala Asp Glu Ser Thr Ser Thr Ala Tyr 65 70 75 80 atg gag ctg age age ctg aga tct gag gac aeg gcc gtg tat tac tgt 288

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 gcg aga agt agt ggt tat tac eet gea tac etc ccc cac tgg ggc cag 336

Ala Arg Ser Ser Gly Tyr Tyr Pro Ala Tyr Leu Pro His Trp Gly Gin 100 105 110 ggc acc ttg gtc acc gtc teg agt get age acc aag ggc ccc age gtg 384

Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val 115 120 125 tte ccc ctg gcc ccc age age aag age acc age ggc ggc aca gcc gcc 432

Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala 130 135 140 ctg ggc tgc ctg gtg aag gac tac tte ccc gag ccc gtg acc gtg age 480

Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser 145 150 155 160 tgg aac age ggc gcc ttg acc age ggc gtg cac acc tte ccc gcc gtg 528

Leu Gin Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro 180 185 190 age age age ctg ggc acc cag acc tac atc tgc aac gtg aac cac aag 624

Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser Cys Asp 210 215 220 aag acc cac acc tgc ccc ccc tgc eet gcc ccc gag ctg ctg ggc gga 720

Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly 225 230 235 240 ccc tee gtg tte ctg tte ccc ccc aag ccc aag gac acc etc atg atc 768

Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu 260 265 270 gac ccc gag gtg aag tte aac tgg tac gtg gac ggc gtg gag gtg cac 864

Val Val Ser Val Leu Thr Val Leu His Gin Asp Trp Leu Asn Gly Lys 305 310 315 320 gag tac aag tgc aag gtg age aac aag gcc ctg eet gcc ccc atc gag 1008

Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gin Val Ser Leu 355 360 365 acc tgt ctg gtg aag gge ttc tac ccc age gac ate gcc gtg gag tgg 1152

Glu Ser Asn Gly Gin Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val 385 390 395 400 ctg gac age gac ggc age tte tte ctg tac age aag etc acc gtg gac 1248

Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp 405 410 415 aag age egg tgg cag cag ggc aac gtg tte age tgc age gtg atg cac 1296

Gly Lys 450 <210> 77 <211 >450

<212> PRT <213> Homo sapiens <400> 77

Glu Val Gin Leu Val Glu Ser Gly Ala Glu Val Lys Lys Pro Gly Ser 15 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Ser Ser Tyr 20 25 30

Gly Ile Ser Trp Val Arg Gin Ala Pro Gly Gin Gly Leu Glu Trp Met 35 40 45

Gly Asp Ile Ile Gly Met Phe Gly Ser Thr Asn Tyr Ala Gin Asn Phe 50 55 60

Gin Gly Arg Leu Thr Ile Thr Ala Asp Glu Ser Thr Ser Thr Ala Tyr 65 70 75 80

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95

Ala Arg Ser Ser Gly Tyr Tyr Pro Ala Tyr Leu Pro His Trp Gly Gin 100 105 110

Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val 115 120 125

Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala 130 135 140

Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser 145 150 155 160

Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val 165 170 175

Leu Gin Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro 180 185 190

Ser Ser Ser Leu Gly Thr Gin Thr Tyr Ile Cys Asn Val Asn His Lys 195 200 205

Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser Cys Asp 210 215 220

Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly 225 230 235 240

Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met lie 245 250 255

Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu 260 265 270

Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His 275 280 285

Asn Ala Lys Thr Lys Pro Arg Glu Glu Gin Tyr Asn Ser Thr Tyr Arg 290 295 300

Val Val Ser Val Leu Thr Val Leu His Gin Asp Trp Leu Asn Gly Lys 305 310 315 320

Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro lie Glu 325 330 335

Lys Thr lie Ser Lys Ala Lys Gly Gin Pro Arg Glu Pro Gin Val Tyr 340 345 350

Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gin Val Ser Leu 355 360 365

Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp lie Ala Val Glu Trp 370 375 380

Glu Ser Asn Gly Gin Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val 385 390 395 400

Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp 405 410 415

Lys Ser Arg Trp Gin Gin Gly Asn Val Phe Ser Cys Ser Val Met His 420 425 430

Glu Ala Leu His Asn His Tyr Thr Gin Lys Ser Leu Ser Leu Ser Pro 435 440 445

Gly Lys 450 <210> 78 <211> 1353

<212> DNA <213> Homo sapiens <220> <221 > CDS <222> (1)..(1353) <400> 78 gag gtg cag ctg gtg gag tct ggg get gag gtg aag aag ccg ggg tee 48

Glu Val Gin Leu Val Glu Ser Gly Ala Glu Val Lys Lys Pro Gly Ser 15 10 15 teg gtg aag gtc tee tgc aag get tct gga ggc ace ttc age ttc tat 96

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Ser Phe Tyr 20 25 30 tct atg age tgg gtg ega cag gee cct gga caa gga ett gag tgg atg 144

Ser Met Ser Trp Val Arg Gin Ala Pro Gly Gin Gly Leu Glu Trp Met 35 40 45 gga ggg ate ate cct atg ttt ggt aca aca aac tac gca cag aag ttc 192

Gly Gly lie lie Pro Met Phe Gly Thr Thr Asn Tyr Ala Gin Lys Phe 50 55 60 cag ggc aga gtc aeg att aec geg gtc gaa tee aeg age aca gee tac 240

Gin Gly Arg Val Thr lie Thr Ala Val Glu Ser Thr Ser Thr Ala Tyr 65 70 75 80 atg gag gtg age age ctg aga tct gag gac aeg gee gtt tat tac tgt 288

Met Glu Val Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 geg aga ggt gat aag ggt ate tac tac tac tac atg gac gtc tgg ggc 336

Ala Arg Gly Asp Lys Gly lie Tyr Tyr Tyr Tyr Met Asp Val Trp Gly 100 105 110 aaa ggg ace aeg gtc ace gtc teg agt get age acc aag ggc ccc age 384

Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala 165 Π0 175 gtg ctg cag age age ggc ctg tac age ctg age age gtg gtg acc gtg 576

Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gin Val Ser 355 360 365 etc acc tgt ctg gtg aag ggc tte tac ccc age gac atc gcc gtg gag 1152

Pro Gly Lys 450 <210> 79 <211 > 451

<212> PRT <213> Homo sapiens <400> 79

Glu Val Gin Leu Val Glu Ser Gly Ala Glu Val Lys Lys Pro Gly Ser 15 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Ser Phe Tyr 20 25 30

Ser Met Ser Trp Val Arg Gin Ala Pro Gly Gin Gly Leu Glu Trp Met 35 40 45

Gly Gly Ile Ile Pro Met Phe Gly Thr Thr Asn Tyr Ala Gin Lys Phe 50 55 60

Gin Gly Arg Val Thr Ile Thr Ala Val Glu Ser Thr Ser Thr Ala Tyr 65 70 75 80

Met Glu Val Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95

Ala Arg Gly Asp Lys Gly Ile Tyr Tyr Tyr Tyr Met Asp Val Trp Gly 100 105 110

Lys Gly Thr Thr Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser 115 120 125

Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala 130 135 140

Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val 145 150 155 160

Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala 165 170 175

Val Leu Gin Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val 180 185 190

Pro Ser Ser Ser Leu Gly Thr Gin Thr Tyr Ile Cys Asn Val Asn His 195 200 205

Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser Cys 210 215 220

Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly 225 230 235 240

Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met 245 250 255

Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His 260 265 270

Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val 275 280 285

His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gin Tyr Asn Ser Thr Tyr 290 295 300

Arg Val Val Ser Val Leu Thr Val Leu His Gin Asp Trp Leu Asn Gly 305 310 315 320

Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile 325 330 335

Glu Lys Thr Ile Ser Lys Ala Lys Gly Gin Pro Arg Glu Pro Gin Val 340 345 350

Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gin Val Ser 355 360 365

Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp ile Ala Val Glu 370 375 380

Trp Glu Ser Asn Gly Gin Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro 385 390 395 400

Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val 405 410 415

Asp Lys Ser Arg Trp Gin Gin Gly Asn Val Phe Ser Cys Ser Val Met 420 425 430

His Glu Ala Leu His Asn His Tyr Thr Gin Lys Ser Leu Ser Leu Ser 435 440 445

Pro Gly Lys 450 <210> 80 <211 > 1350

<212> DNA <213> Homo sapiens <220> <221 > CDS <222> (1)..(1350) <400> 80 gag gtg cag ctg gtg gag tct ggg get gag gtg aag aag cct ggg tee 48

Glu Val Gin Leu Val Glu Ser Gly Ala Glu Val Lys Lys Pro Gly Ser 15 10 15 teg gtg aag gtc tee tgc aag get tct gga ggc ace ttc age age tat 96

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Ser Ser Tyr 20 25 30 get ate age tgg gtg ega cag gee cct gga eaa ggg ett gag tgg atg 144

Ala Ile Ser Trp Val Arg Gin Ala Pro Gly Gin Gly Leu Glu Trp Met 35 40 45 gga ggg ate ate ggt atg ttc ggt aca gea aae tac gca cag aag ttc 192

Gly Gly lie lie Gly Met Phe Gly Thr Ala Asn Tyr Ala Gin Lys Phe 50 55 60 cag ggc aga gtc aeg att acc geg gac gaa ttt aeg age aca gee tac 240

Gin Gly Arg Val Thr lie Thr Ala Asp Glu Phe Thr Ser Thr Ala Tyr 65 70 75 80 atg gag ctg age age ctg aga tct gag gac aeg gee gtg tat tac tgt 288

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 geg aga gga aat tat tac tat gag agt agt etc gac tac tgg ggc cag 336

Ala Arg Gly Asn Tyr Tyr Tyr Glu Ser Ser Leu Asp Tyr Trp Gly Gin 100 105 110 gga acc ctg gtc acc gtc teg agt get age acc aag ggc ccc age gtg 384

Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val 115 120 125 tte ccc ctg gee ccc age age aag age acc age ggc ggc aca gee gee 432

Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser 145 150 155 160 tgg aae age ggc gee ttg acc age ggc gtg cac acc ttc ccc gee gtg 528

Leu Gin Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro 180 185 190 age age age etg ggc acc cag acc tac atc tgc aac grtg aac cae aag €24

Ser Ser Ser Leu Gly Thr Gin Thr Tyr Ile Cys Asn Val Asn His Lys 195 200 205 ccc age aac acc aag gtg gac aaa cgc gtg gag ccc aag age tgc gac 672

Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly 225 230 235 240 ccc tee gtg ttc ctg ttc ccc ccc aag ccc aag gac acc ctc atg atc 768

Asn Ala Lys Thr Lys Pro Arg Glu Glu Gin Tyr Asn Ser Thr Tyr Arg 290 295 300 gtg gtg age gtg ctc acc gtg ctg cac cag gac tgg ctg aac ggc aag 960

Lys Thr Ile Ser Lys Ala Lys Gly Gin Pro Arg Glu Pro Gin Val Tyr 340 345 350 acc ctg ccc ccc age egg gag gag atg acc aag aac cag gtg tee ctc 1104

Glu Ser Asn Gly Gin Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val 385 390 395 400 ctg gac age gac ggc age ttc ttc ctg tac age aag ctc acc gtg gac 1248

Gly Lys 450 <210>81 <211 >450

<212> PRT <213> Homo sapiens <400 81

Glu Val Gin Leu Val Glu Ser Gly Ala Glu Val Lys Lys Pro Gly Ser 15 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Ser Ser Tyr 20 25 30

Ala Ile Ser Trp Val Arg Gin Ala Pro Gly Gin Gly Leu Glu Trp Met 35 40 45

Gly Gly Ile Ile Gly Met Phe Gly Thr Ala Asn Tyr Ala Gin Lys Phe 50 55 60

Gin Gly Arg Val Thr Ile Thr Ala Asp Glu Phe Thr Ser Thr Ala Tyr 65 70 75 80

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95

Ala Arg Gly Asn Tyr Tyr Tyr Glu Ser Ser Leu Asp Tyr Trp Gly Gin 100 105 110

Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val 115 120 125

Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala 130 135 140

Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser 145 150 155 160

Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val 165 170 175

Leu Gin Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro 180 185 190

Ser Ser Ser Leu Gly Thr Gin Thr Tyr Ile Cys Asn Val Asn His Lys 195 200 205

Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser Cys Asp 210 215 220

Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly 225 230 235 240

Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met ile 245 250 255

Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu 260 265 270

Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His 275 280 285

Asn Ala Lys Thr Lys Pro Arg Glu Glu Gin Tyr Asn Ser Thr Tyr Arg 290 295 300

Val Val Ser Val Leu Thr Val Leu His Gin Asp Trp Leu Asn Gly Lys 305 310 315 320

Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu 325 330 335

Lys Thr Ile Ser Lys Ala Lys Gly Gin Pro Arg Glu Pro Gin Val Tyr 340 345 350

Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gin val Ser Leu 355 360 365

Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp 370 375 380

Glu Ser Asn Gly Gin Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val 385 390 395 400

Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp 405 410 415

Lys Ser Arg Trp Gin Gin Gly Asn Val Phe Ser Cys Ser Val Met His 420 425 430

Glu Ala Leu His Asn Kis Tyr Thr Gin Lys Ser Leu Ser Leu Ser Pro 435 440 445

Gly Lys 450 <210> 82 <211 > 1359

<212> DNA <213> Homo sapiens <220> <221 > CDS <222> (1)..(1359) <400> 82 cag gtg cag ctg gtg cag tct ggg get gag gtg aag aag cct ggg tee 48

Gin Val Gin Leu Val Gin Ser Gly Ala Glu Val Lys Lys Pro Gly Ser 15 10 15 teg gtg aga gtc tee tgc aag get tct gga age ate ttc aga aac tat 96

Ser Val Arg Val Ser Cys Lys Ala Ser Gly Ser Ile Phe Arg Asn Tyr 20 25 30 get atg age tgg gtg ega cag gee cct gga caa ggg ett gag tgg atg 144

Ala Met Ser Trp Val Arg Gin Ala Pro Gly Gin Gly Leu Glu Trp Met 35 40 45 gga ggg ate ate get att ttt ggg aca cca aag tac gca cag aag ttc 192

Gly Gly lie lie Ala lie Phe Gly Thr Pro Lys Tyr Ala Gin Lys Phe 50 55 €0 cag ggc aga gtc aeg att acc geg gac gaa teg aeg age act gtc tac 240

Gin Gly Arg Val Thr lie Thr Ala Asp Glu Ser Thr Ser Thr Val Tyr 65 70 75 80 atg gaa ctg age gga ctg aga tct gag gac aeg gee atg tat tac tgt 288

Met Glu Leu Ser Gly Leu Arg Ser Glu Asp Thr Ala Met Tyr Tyr Cys 85 90 95 geg agg att ccc cac tat aat ttt ggt teg ggg agt tat ttc gac tac 336

Ala Arg lie Pro His Tyr Asn Phe Gly Ser Gly Ser Tyr Phe Asp Tyr 100 105 110 tgg ggc cag gga acc ctg gtc acc gtc teg agt get age acc aag ggc 384

Trp Gly Gin Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly 115 120 125 ccc age gtg ttc ccc ctg gee ccc age age aag age acc age ggc ggc 432

Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly 130 135 140 aca gee gee ctg ggc tgc ctg gtg aag gac tac ttc ccc gag ccc gtg 480

Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val 145 150 155 160 acc gtg age tgg aac age ggc gee ttg acc age ggc gtg cac acc ttc 528

Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe 165 170 175 ccc gee gtg ctg cag age age ggc ctg tac age ctg age age gtg gtg 576

Pro Ala Val Leu Gin Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val 180 185 190 acc gtg ccc age age age ctg ggc acc cag acc tac ate tgc aac gtg 624

Thr Val Pro Ser Ser Ser Leu Gly Thr Gin Thr Tyr lie Cys Asn Val 195 200 205 aac cac aag ccc age aac acc aag gtg gac aaa ege gtg gag ccc aag 672

Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys 210 215 220 age tgc gac aag acc cac acc tgc ccc ccc tgc cct gee ccc gag ctg 720

Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu 225 230 235 240 ctg ggc gga ccc tee gtg ttc ctg ttc ccc ccc aag ccc aag gac acc 768

Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr 245 250 255 etc atg ate age egg acc ccc gag gtg acc tgc gtg gtg gtg gac gtg 816

Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val 260 265 270 age cac gag gac ccc gag gtg aag ttc aac tgg tac gtg gac ggc gtg 864

Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val 275 280 285 gag gtg cac aac gee aag acc aag ccc egg gag gag cag tac aac age 912

Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gin Tyr Asn Ser 290 295 300 acc tac egg gtg gtg age gtg etc acc gtg ctg cac cag gac tgg ctg 960

Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gin Asp Trp Leu 305 310 315 320 aac ggc aag gag tac aag tgc aag gtg age aac aag gee ctg cct gee 1008

Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala 325 330 335 ccc ate gag aag acc ate age aag gee aag ggc cag ccc egg gag ccc 1056

Pro lie Glu Lys Thr lie Ser Lys Ala Lys Gly Gin Pro Arg Glu Pro 340 345 350 cag gtg tac acc ctg ccc ccc age egg gag gag atg acc aag aac cag 1104

Gin Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gin 355 360 365 gtg tee etc acc tgt ctg gtg aag ggc ttc tac ccc age gac ate gee 1152

Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp lie Ala 370 375 380 gtg gag tgg gag age aac ggc cag ccc gag aac aac tac aag acc acc 1200

Val Glu Trp Glu Ser Asn Gly Gin Pro Glu Asn Asn Tyr Lys Thr Thr 385 390 395 400 ccc cct gtg ctg gac age gac ggc age ttc ttc ctg tac age aag etc 1248

Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu 405 410 415 acc gtg gac aag age egg tgg cag cag ggc aac gtg ttc age tgc age 1296

Thr Val Asp Lys Ser Arg Trp Gin Gin Gly Asn Val Phe Ser Cys Ser 420 425 430 gtg atg cac gag gee ctg cac aac cac tac acc cag aag age ctg age 1344

Val Met His Glu Ala Leu His Asn His Tyr Thr Gin Lys Ser Leu Ser 435 440 445 ctg age ccc ggc aag 1359

Leu Ser Pro Gly Lys 450 <210> 83 <211 >453

<212> PRT <213> Homo sapiens <400> 83

Gin Val Gin Leu Val Gin Ser Gly Ala Glu Val Lys Lys Pro Gly Ser 15 10 15

Ser Val Arg Val Ser Cys Lys Ala Ser Gly Ser Ile Phe Arg Asn Tyr 20 25 30

Ala Met Ser Trp Val Arg Gin Ala Pro Gly Gin Gly Leu Glu Trp Met 35 40 45

Gly Gly lie lie Ala lie Phe Gly Thr Pro Lys Tyr Ala Gin Lys Phe 50 55 60

Gin Gly Arg Val Thr Ile Thr Ala Asp Glu Ser Thr Ser Thr Val Tyr 65 70 75 80

Met Glu Leu Ser Gly Leu Arg Ser Glu Asp Thr Ala Met Tyr Tyr Cys 85 90 95

Ala Arg lie Pro His Tyr Asn Phe Gly Ser Gly Ser Tyr Phe Asp Tyr 100 105 110

Trp Gly Gin Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly 115 120 125

Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly 130 135 140

Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val 145 150 155 160

Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe 165 170 175

Pro Ala Val Leu Gin Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val 180 185 190

Thr Val Pro Ser Ser Ser Leu Gly Thr Gin Thr Tyr lie Cys Asn Val 195 200 205

Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys 210 215 220

Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu 225 230 235 240

Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr 245 250 255

Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val 260 265 270

Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val 275 280 285

Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gin Tyr Asn Ser 290 295 300

Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gin Asp Trp Leu 305 310 315 320

Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala 325 330 335

Pro lie Glu Lys Thr lie Ser Lys Ala Lys Gly Gin Pro Arg Glu Pro 340 345 350

Gin Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gin 355 360 365

Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp lie Ala 370 375 380

Val Glu Trp Glu Ser Asn Gly Gin Pro Glu Asn Asn Tyr Lys Thr Thr 385 390 395 400

Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu 405 410 415

Thr Val Asp Lys Ser Arg Trp Gin Gin Gly Asn Val Phe Ser Cys Ser 420 425 430

Val Met His Glu Ala Leu His Asn His Tyr Thr Gin Lys Ser Leu Ser 435 440 445

Leu Ser Pro Gly Lys 450 <210> 84 <211 > 660

<212> DNA <213> Homo sapiens <220> <221 > CDS <222> (1)..(660) <400> 84 tcc tat gtg ctg act cag cca ccc tea gcg tet ggg acc ccc ggg cag 48

Ser Tyr Val Leu Thr Gin Pro Pro Ser Ala Ser Gly Thr Pro Gly Gin 15 10 15 agg gtc acc atc tet tgt tet gga age aeg tte aac atc gga agt aat 96

Arg Val Thr Ile Ser Cys Ser Gly Ser Thr Phe Asn Ile Gly Ser Asn 20 25 30 get gta gac tgg tac egg cag etc cca gga aeg gee ccc aaa etc etc 144

Ala Val Asp Trp Tyr Arg Gin Leu Pro Gly Thr Ala Pro Lys Leu Leu 35 40 45 atc tat agt aat aat cag egg ccc tea ggg gtc eet gac ega tte tet 192

Ile Tyr Ser Asn Asn Gin Arg Pro Ser Gly Val Pro Asp Arg Phe Ser 50 55 60 ggc tee agg tet ggc acc tea gee tec ctg gee atc agt ggg etc cag 240

Gly Ser Arg Ser Gly Thr Ser Ala Ser Leu Ala Ile Ser Gly Leu Gin 65 70 75 80 tet gag gat gag get gat tat tac tgt gea gea tgg gat gac atc ctg 288

Ser Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Ala Trp Asp Asp Ile Leu 85 90 95 aat gtt ccg gta tte ggc gga ggg acc aag ctg acc gtc eta ggt gcg 336

Asn Val Pro Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Ala 100 105 110 gcc gea ggc cag ccc aag gee get ccc age gtg acc ctg tte ccc ccc 384

Ala Ala Gly Gin Pro Lys Ala Ala Pro Ser Val Thr Leu Phe Pro Pro 115 120 125 tee tee gag gag ctg cag gee aac aag gee acc ctg gtg tgc etc atc 432

Ser Ser Glu Glu Leu Gin Ala Asn Lys Ala Thr Leu Val Cys Leu Ile 130 135 140 age gac tte tac eet ggc gcc gtg acc gtg gcc tgg aag gcc gac age 480

Ser Asp Phe Tyr Pro Gly Ala Val Thr Val Ala Trp Lys Ala Asp Ser 145 150 155 160 age ccc gtg aag gcc ggc gtg gag acc acc acc ccc age aag cag age 528

Ser Pro Val Lys Ala Gly Val Glu Thr Thr Thr Pro Ser Lys Gin Ser 165 170 175 aac aac aag tac gee gee age age tac ctg age etc acc ccc gag cag 576

Asn Asn Lys Tyr Ala Ala Ser Ser Tyr Leu Ser Leu Thr Pro Glu Gin 180 185 190 tgg aag age cac egg age tac age tgc cag gtg acc cac gag ggc age 624

Trp Lys Ser His Arg Ser Tyr Ser Cys Gin Val Thr His Glu Gly Ser 195 200 205 acc gtg gag aag acc gtg gcc ccc acc gag tgc age 660

Thr Val Glu Lys Thr Val Ala Pro Thr Glu Cys Ser 210 215 220 <210> 85 <211 > 220

<212> PRT <213> Homo sapiens <400> 85

Ser Tyr Val Leu Thr Gin Pro Pro Ser Ala Ser Gly Thr Pro Gly Gin 15 10 15

Arg Val Thr Ile Ser Cys Ser Gly Ser Thr Phe Asn Ile Gly Ser Asn 20 25 30

Ala Val Asp Trp Tyr Arg Gin Leu Pro Gly Thr Ala Pro Lys Leu Leu 35 40 45

Ile Tyr Ser Asn Asn Gin Arg Pro Ser Gly Val Pro Asp Arg Phe Ser 50 55 60

Gly Ser Arg Ser Gly Thr Ser Ala Ser Leu Ala Ile Ser Gly Leu Gin 65 70 75 80

Ser Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Ala Trp Asp Asp Ile Leu 85 90 95

Asn Val Pro Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Ala 100 105 110

Ala Ala Gly Gin Pro Lys Ala Ala Pro Ser Val Thr Leu Phe Pro Pro 115 120 125

Ser Ser Glu Glu Leu Gin Ala Asn Lys Ala Thr Leu Val Cys Leu Ile 130 135 140

Ser Asp Phe Tyr Pro Gly Ala Val Thr Val Ala Trp Lys Ala Asp Ser 145 150 155 160

Ser Pro Val Lys Ala Gly Val Glu Thr Thr Thr Pro Ser Lys Gin Ser 165 170 175

Asn Asn Lys Tyr Ala Ala Ser Ser Tyr Leu Ser Leu Thr Pro Glu Gin 180 185 190

Trp Lys Ser His Arg Ser Tyr Ser Cys Gin Val Thr His Glu Gly Ser 195 200 205

Thr Val Glu Lys Thr Val Ala Pro Thr Glu Cys Ser 210 215 220 <210> 86 <211 > 660

<212> DNA <213> Homo sapiens <220> <221 > CDS <222> (1)..(660) <400> 86 cag tct gcc ctg act cag cct gcc gcc gtg tct ggg tct cct gga cag 48

Gin Ser Ala Leu Thr Gin Pro Ala Ala Val Ser Gly Ser Pro Gly Gin 15 10 15 teg ate acc ate tec tgc act gga acc age agt gac gtt ggt ggt tat 96

Ser Ile Thr Ile Ser Cys Thr Gly Thr Ser Ser Asp Val Gly Gly Tyr 20 25 30 aac tat gtc tcc tgg tac caa cag cac cca ggc aaa gcc ccc aaa etc 144

Asn Tyr Val Ser Trp Tyr Gin Gin His Pro Gly Lys Ala Pro Lys Leu 35 40 45 atg att tat gag gtc agt aat egg ccc tea ggg gtt tct aat ege ttc 192

Met Ile Tyr Glu Val Ser Asn Arg Pro Ser Gly Val Ser Asn Arg Phe 50 55 60 tct ggc tcc aag tct ggc aac aeg gcc tcc ctg acc ate tct ggg etc 240

Ser Gly Ser Lys Ser Gly Asn Thr Ala Ser Leu Thr lie Ser Gly Leu 65 70 75 80 cag get gag gac gag get gat tat tac tgc age tea tat aca age age 288

Gin Ala Glu Asp Glu Ala Asp Tyr Tyr Cys Ser Ser Tyr Thr Ser Ser 85 90 95 age act tat gtc ttc gga act ggg acc aag gtc acc gtc eta ggt geg 336

Ser Thr Tyr Val Phe Gly Thr Gly Thr Lys Val Thr Val Leu Gly Ala 100 105 110 gcc gca ggc cag ccc aag gcc get ccc age gtg acc ctg ttc ccc ccc 384

Ala Ala Gly Gin Pro Lys Ala Ala Pro Ser Val Thr Leu Phe Pro Pro 115 120 125 tcc tcc gag gag ctg cag gcc aac aag gcc acc ctg gtg tgc etc ate 432

Ser Ser Glu Glu Leu Gin Ala Asn Lys Ala Thr Leu Val Cys Leu lie 130 135 140 age gac ttc tac cct ggc gcc gtg acc gtg gcc tgg aag gcc gac age 480

Ser Pro Val Lys Ala Gly Val Glu Thr Thr Thr Pro Ser Lys Gin Ser 165 170 175 aac aac aag tac gcc gcc age age tac ctg age etc acc ccc gag cag 576

Thr Val Glu Lys Thr Val Ala Pro Thr Glu Cys Ser 210 215 220 <210> 87 <211 > 220

<212> PRT <213> Homo sapiens <400> 87

Gin Ser Ala Leu Thr Gin Pro Ala Ala Val Ser Gly Ser Pro Gly Gin 15 10 15

Ser Ile Thr Ile Ser Cys Thr Gly Thr Ser Ser Asp Val Gly Gly Tyr 20 25 30

Asn Tyr Val Ser Trp Tyr Gin Gin His Pro Gly Lys Ala Pro Lys Leu 35 40 45

Met Ile Tyr Glu Val Ser Asn Arg Pro Ser Gly Val Ser Asn Arg Phe 50 55 60

Ser Gly Ser Lys Ser Gly Asn Thr Ala Ser Leu Thr lie Ser Gly Leu 65 70 75 80

Gin Ala Glu Asp Glu Ala Asp Tyr Tyr Cys Ser Ser Tyr Thr Ser Ser 85 90 95

Ser Thr Tyr Val Phe Gly Thr Gly Thr Lys Val Thr Val Leu Gly Ala 100 105 110

Ala Ala Gly Gin Pro Lys Ala Ala Pro Ser Val Thr Leu Phe Pro Pro 115 120 125

Ser Ser Glu Glu Leu Gin Ala Asn Lys Ala Thr Leu Val Cys Leu lie 130 135 140

Ser Asp Phe Tyr Pro Gly Ala Val Thr Val Ala Trp Lys Ala Asp Ser 145 150 155 160

Ser Pro Val Lys Ala Gly Val Glu Thr Thr Thr Pro Ser Lys Gin Ser 165 170 175

Asn Asn Lys Tyr Ala Ala Ser Ser Tyr Leu Ser Leu Thr Pro Glu Gin 180 185 190

Trp Lys Ser His Arg Ser Tyr Ser Cys Gin Val Thr His Glu Gly Ser 195 200 205

Thr Val Glu Lys Thr Val Ala Pro Thr Glu Cys Ser 210 215 220 <210> 88 <211 > 660

<212> DNA <213> Homo sapiens <220> <221 > CDS <222> (1)..(660) <400> 88 tcc tat gtg ctg act cag cca ccc tea gtc tet ggg acc ccc ggg cag 48

Ser Tyr Val Leu Thr Gin Pro Pro Ser Val Ser Gly Thr Pro Gly Gin 15 10 15 agg gtc acc atc tet tgc tet gga age ege tcc aac gtc gga gat aat 96

Arg Val Thr Ile Ser Cys Ser Gly Ser Arg Ser Asn Val Gly Asp Asn 20 25 30 tet gta tat tgg tat caa cac gtc cca gaa atg gee ccc aaa etc etc 144

Ser Val Tyr Trp Tyr Gin His Val Pro Glu Met Ala Pro Lys Leu Leu 35 40 45 gtc tat aag aat act caa egg ccc tea gga gtc eet gee egg ttt tcc 192

Val Tyr Lys Asn Thr Gin Arg Pro Ser Gly Val Pro Ala Arg Phe Ser 50 55 60 ggc tee aag tet ggc act tea gee tec ctg gee atc att ggc etc cag 240

Gly Ser Lys Ser Gly Thr Ser Ala Ser Leu Ala lie lie Gly Leu Gin 65 70 75 80 tec ggc gat gag get gat tat tat tgt gtg gca tgg gat gac age gta 288

Ser Gly Asp Glu Ala Asp Tyr Tyr Cys Val Ala Trp Asp Asp Ser Val 85 90 95 gat ggc tat gtc ttc gga tet ggg acc aag gtc acc gtc eta ggt geg 336

Asp Gly Tyr Val Phe Gly Ser Gly Thr Lys Val Thr Val Leu Gly Ala 100 105 110 gee gca ggc cag ccc aag gee get ccc age gtg acc ctg ttc ccc ccc 384

Ala Ala Gly Gin Pro Lys Ala Ala Pro Ser Val Thr Leu Phe Pro Pro 115 120 125 tec tec gag gag ctg cag gee aac aag gee acc ctg gtg tgc etc atc 432

Ser Ser Glu Glu Leu Gin Ala Asn Lys Ala Thr Leu Val Cys Leu lie 130 135 140 age gac ttc tac cct ggc gee gtg acc gtg gee tgg aag gee gac age 480

Ser Asp Phe Tyr Pro Gly Ala Val Thr Val Ala Trp Lys Ala Asp Ser 145 150 155 160 age ccc gtg aag gee ggc gtg gag acc acc acc ccc age aag cag age 528

Trp Lys Ser His Arg Ser Tyr Ser Gys Gin Val Thr His Glu Gly Ser 195 200 205 acc gtg gag aag acc gtg gee ccc acc gag tgc age 660

Thr Val Glu Lys Thr Val Ala Pro Thr Glu Cys Ser 210 215 220 <210> 89 <211 > 220

<212> PRT <213> Homo sapiens <400> 89

Ser Tyr Val Leu Thr Gin Pro Pro Ser Val Ser Gly Thr Pro Gly Gin 15 10 15

Arg Val Thr Ile Ser Cys Ser Gly Ser Arg Ser Asn Val Gly Asp Asn 20 25 30

Ser Val Tyr Trp Tyr Gin His Val Pro Glu Met Ala Pro Lys Leu Leu 35 40 45

Val Tyr Lys Asn Thr Gin Arg Pro Ser Gly Val Pro Ala Arg Phe Ser 50 55 60

Gly Ser Lys Ser Gly Thr Ser Ala Ser Leu Ala Ile Ile Gly Leu Gin 65 70 75 80

Ser Gly Asp Glu Ala Asp Tyr Tyr Cys Val Ala Trp Asp Asp Ser Val 85 90 95

Asp Gly Tyr Val Phe Gly Ser Gly Thr Lys Val Thr Val Leu Gly Ala 100 105 110

Ala Ala Gly Gin Pro Lys Ala Ala Pro Ser Val Thr Leu Phe Pro Pro 115 120 125

Ser Ser Glu Glu Leu Gin Ala Asn Lys Ala Thr Leu Val Cys Leu Ile 130 135 140

Ser Asp Phe Tyr Pro Gly Ala Val Thr Val Ala Trp Lys Ala Asp Ser 145 150 155 160

Ser Pro Val Lys Ala Gly Val Glu Thr Thr Thr Pro Ser Lys Gin Ser 165 170 175

Asn Asn Lys Tyr Ala Ala Ser Ser Tyr Leu Ser Leu Thr Pro Glu Gin 180 185 190

Trp Lys Ser His Arg Ser Tyr Ser Cys Gin Val Thr His Glu Gly Ser 195 200 205

Thr Val Glu Lys Thr Val Ala Pro Thr Glu Cys Ser 210 215 220 <210> 90 <211 > 663

<212> DNA <213> Homo sapiens <220> <221 > CDS <222> (1)..(663) <400> 90 cag tct gtg ttg acg cag ccg ccc tea gtg tet geg gee cca gga cag 48

Gin Ser Val Leu Thr Gin Pro Pro Ser Val Ser Ala Ala Pro Gly Gin 15 10 15 aag gtc ace ate tee tgc tct gga age age tee aac att ggg aat gat 96

Lys Val Thr lie Ser Cys Ser Gly Ser Ser Ser Asn lie Gly Asn Asp 20 25 30 tat gta tee tgg tac cag cag etc cca gga aca gee ccc aaa etc etc 144

Tyr Val Ser Trp Tyr Gin Gin Leu Pro Gly Thr Ala Pro Lys Leu Leu 35 40 45 att tat gac aat aat aag ega ccc tea ggg att cct gac ega ttc tct 192

Ile Tyr Asp Asn Asn Lys Arg Pro Ser Gly lie Pro Asp Arg Phe Ser 50 55 60 ggc tee aag tct ggc acg tea gee acc ctg ggc ate ace gga etc cag 240

Gly Ser Lys Ser Gly Thr Ser Ala Thr Leu Gly lie Thr Gly Leu Gin 65 70 75 80 act ggg gac gag gee aac tat tae tgc gca aea tgg gat ege ege ccg 288

Thr Gly Asp Glu Ala Asn Tyr Tyr Cys Ala Thr Trp Asp Arg Arg Pro 85 90 95 act get tat gtt gtc ttc ggc gga ggg acc aag ctg acc gtc eta ggt 336

Thr Ala Tyr Val Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly 100 105 110 geg gee gca ggc cag ccc aag gee get ccc age gtg acc ctg ttc ccc 384

Ala Ala Ala Gly Gin Pro Lys Ala Ala Pro Ser Val Thr Leu Phe Pro 115 120 125 ccc tee tee gag gag ctg cag gee aac aag gee acc ctg gtg tgc etc 432

Pro Ser Ser Glu Glu Leu Gin Ala Asn Lys Ala Thr Leu Val Cys Leu 130 135 140 ate age gac ttc tac cct ggc gee gtg acc gtg gee tgg aag gee gac 480 lie Ser Asp Phe Tyr Pro Gly Ala Val Thr Val Ala Trp Lys Ala Asp 145 150 155 160 age age ccc gtg aag gee ggc gtg gag acc acc acc ccc age aag cag 528

Ser Ser Pro Val Lys Ala Gly Val Glu Thr Thr Thr Pro Ser Lys Gin 165 170 175 age aac aac aag tac gee gee age age tac ctg age etc acc ccc gag 576

Ser Asn Asn Lys Tyr Ala Ala Ser Ser Tyr Leu Ser Leu Thr Pro Glu 180 185 190 cag tgg aag age cac egg age tac age tgc cag gtg acc cac gag ggc 624

Gin Trp Lys Ser His Arg Ser Tyr Ser Cys Gin Val Thr His Glu Gly 195 200 205 age acc gtg gag aag acc gtg gee ccc acc gag tgc age 663

Ser Thr Val Glu Lys Thr Val Ala Pro Thr Glu Cys Ser 210 215 220 <210> 91 <211> 221

<212> PRT <213> Homo sapiens <400> 91

Gin Ser Val Leu Thr Gin Pro Pro Ser Val Ser Ala Ala Pro Gly Gin 15 10 15

Lys Val Thr Ile Ser Cys Ser Gly Ser Ser Ser Asn Ile Gly Asn Asp 20 25 30

Tyr Val Ser Trp Tyr Gin Gin Leu Pro Gly Thr Ala Pro Lys Leu Leu 35 40 45

Ile Tyr Asp Asn Asn Lys Arg Pro Ser Gly Ile Pro Asp Arg Phe Ser 50 55 60

Gly Ser Lys Ser Gly Thr Ser Ala Thr Leu Gly Ile Thr Gly Leu Gin 65 70 75 80

Thr Gly Asp Glu Ala Asn Tyr Tyr Cys Ala Thr Trp Asp Arg Arg Pro 85 90 95

Thr Ala Tyr Val Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly 100 105 110

Ala Ala Ala Gly Gin Pro Lys Ala Ala Pro Ser Val Thr Leu Phe Pro 115 120 125

Pro Ser Ser Glu Glu Leu Gin Ala Asn Lys Ala Thr Leu Val Cys Leu 130 135 140

Ile Ser Asp Phe Tyr Pro Gly Ala Val Thr Val Ala Trp Lys Ala Asp 145 150 155 160

Ser Ser Pro Val Lys Ala Gly Val Glu Thr Thr Thr Pro Ser Lys Gin 165 170 175

Ser Asn Asn Lys Tyr Ala Ala Ser Ser Tyr Leu Ser Leu Thr Pro Glu 180 185 190

Gin Trp Lys Ser His Arg Ser Tyr Ser Cys Gin Val Thr His Glu Gly 195 200 205

Ser Thr Val Glu Lys Thr Val Ala Pro Thr Glu Cys Ser 210 215 220 <210> 92 <211 > 642

<212> DNA <213> Homo sapiens <220> <221 > CDS <222> (1)..(642) <400> 92 gac ate cag atg acc cag tet cca tee tee ctg tet gca tet gta gga 48

Asp lie Gin Met Thr Gin Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 15 10 15 gac aga gtc acc ate act tgc egg geg agt cag ggc att age agt tat 96

Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gin Gly Ile Ser Ser Tyr 20 25 30 tta gee tgg tat eag cag aag cca ggg aaa gtt cct aca etc ctg ate 144

Leu Ala Trp Tyr Gin Gin Lys Pro Gly Lys Val Pro Thr Leu Leu lie 35 40 45 tat gat gca tee act ttg ega tea ggg gtc cca tet ege ttc agt ggc 192

Tyr Asp Ala Ser Thr Leu Arg Ser Gly Val Pro Ser Arg Phe Ser Gly 50 55 60 agt gga tet geg aca gat ttc act etc acc ate age age ctg cag cct 240

Ser Gly Ser Ala Thr Asp Phe Thr Leu Thr lie Ser Ser Leu Gin Pro 65 70 75 80 gaa gat gtt gca act tat tae tgt caa agg tat aac agt gee ccc ccg 288

Glu Asp Val Ala Thr Tyr Tyr Cys Gin Arg Tyr Asn Ser Ala Pro Pro 85 90 95 ate acc ttc ggc caa ggg aca ega ctg gag att aaa cgt geg gee gca 336 lie Thr Phe Gly Gin Gly Thr Arg Leu Glu lie Lys Arg Ala Ala Ala 100 105 110 ccc age gtg ttc ate ttc ccc ccc tee gac gag cag ctg aag age ggc 384

Pro Ser Val Phe lie Phe Pro Pro Ser Asp Glu Gin Leu Lys Ser Gly 115 120 125 acc gee age gtg gtg tgc ctg ctg aac aac ttc tae ccc egg gag gee 432

Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala 130 135 140 aag gtg cag tgg aag gtg gac aac gee ctg cag age ggc aac age cag 480

Lys Val Gin Trp Lys Val Asp Asn Ala Leu Gin Ser Gly Asn Ser Gin 145 150 155 160 gag age gtg acc gag cag gac age aag gac tee acc tae age ctg age 528

Glu Ser Val Thr Glu Gin Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser 165 170 175 age acc etc acc ctg age aag gee gac tae gag aag cac aag gtg tae 576

Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr 180 185 190 gee tgc gag gtg acc cac cag ggc ctg age age ccc gtg acc aag age 624

Ala Cys Glu Val Thr His Gin Gly Leu Ser Ser Pro Val Thr Lys Ser 195 200 205 ttc aac egg ggc gag tgt 642

Phe Asn Arg Gly Glu Cys 210 <210> 93 <211 > 214

<212> PRT <213> Homo sapiens <400> 93

Asp Ile Gin Met Thr Gin Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 15 10 15

Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gin Gly Ile Ser Ser Tyr 20 25 30

Leu Ala Trp Tyr Gin Gin Lys Pro Gly Lys Val Pro Thr Leu Leu lie 35 40 45

Tyr Asp Ala Ser Thr Leu Arg Ser Gly Val Pro Ser Arg Phe Ser Gly 50 55 60

Ser Gly Ser Ala Thr Asp Phe Thr Leu Thr lie Ser Ser Leu Gin Pro 65 70 75 80

Glu Asp Val Ala Thr Tyr Tyr Cys Gin Arg Tyr Asn Ser Ala Pro Pro 85 90 95 lie Thr Phe Gly Gin Gly Thr Arg Leu Glu He Lys Arg Ala Ala Ala 100 105 110

Pro Ser Val Phe He Phe Pro Pro Ser Asp Glu Gin Leu Lys Ser Gly 115 120 125

Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala 130 135 140

Lys Val Gin Trp Lys Val Asp Asn Ala Leu Gin Ser Gly Asn Ser Gin 145 150 155 160

Glu Ser Val Thr Glu Gin Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser 165 170 175

Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr 180 185 190

Ala Cys Glu Val Thr His Gin Gly Leu Ser Ser Pro Val Thr Lys Ser 195 200 205

Phe Asn Arg Gly Glu Cys 210 <210> 94 <211 > 648

<212> DNA <213> Homo sapiens <220> <221 > CDS <222> (1)..(648) <400> 94 cag tct gtg ctg act cag cca ccc tea gag tee gtg tee cca gga cag 48

Gin Ser Val Leu Thr Gin Pro Pro Ser Glu Ser Val Ser Pro Gly Gin 15 10 15 aca gee age gtc ace tgc tct gga cat aaa ttg ggg gat aaa tat gtt 96

Thr Ala Ser Val Thr Cys Ser Gly His Lys Leu Gly Asp Lys Tyr Val 20 25 30 teg tgg tat cag cag aag cca ggc cag tee cct gta tta etc ate tat 144

Ser Trp Tyr Gin Gin Lys Pro Gly Gin Ser Pro Val Leu Leu lie Tyr 35 40 45 caa gat aac agg egg ecc tea ggg ate cct gag ega ttc ata ggc tee 192

Gin Asp Asn Arg Arg Pro Ser Gly lie Pro Glu Arg Phe lie Gly Ser 50 55 60 aac tct ggg aac aca gee act ctg acc ate age ggg acc cag get ctg 240

Asn Ser Gly Asn Thr Ala Thr Leu Thr lie Ser Gly Thr Gin Ala Leu 65 70 75 80 gat gag get gac tat tac tgt cag geg tgg gac age age act geg gtt 288

Asp Glu Ala Asp Tyr Tyr Cys Gin Ala Trp Asp Ser Ser Thr Ala Val 85 90 95 ttc ggc gga ggg acc aag ctg acc gtc eta ggt geg gee gca ggc cag 336

Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Ala Ala Ala Gly Gin 100 105 110 ccc aag gee get ccc age gtg acc ctg ttc ccc ccc tee tee gag gag 384

Pro Lys Ala Ala Pro Ser Val Thr Leu Phe Pro Pro Ser Ser Glu Glu 115 120 125 ctg cag gee aac aag gee acc ctg gtg tgc etc ate age gac ttc tac 432

Leu Gin Ala Asn Lys Ala Thr Leu Val Cys Leu lie Ser Asp Phe Tyr 130 135 140 cct ggc gee gtg acc gtg gee tgg aag gee gac age age ccc gtg aag 480

Pro Gly Ala Val Thr Val Ala Trp Lys Ala Asp Ser Ser Pro Val Lys 145 150 155 160 gee ggc gtg gag acc acc acc ccc age aag cag age aac aac aag tac 528

Ala Gly Val Glu Thr Thr Thr Pro Ser Lys Gin Ser Asn Asn Lys Tyr 165 170 175 gee gee age age tac ctg age etc acc ccc gag cag tgg aag age cac 576

Ala Ala Ser Ser Tyr Leu Ser Leu Thr Pro Glu Gin Trp Lys Ser His 180 185 190 egg age tac age tgc cag gtg acc cac gag ggc age acc gtg gag aag 624

Arg Ser Tyr Ser Cys Gin Val Thr His Glu Gly Ser Thr Val Glu Lys 195 200 205 acc gtg gee ccc acc gag tgc age 648

Thr Val Ala Pro Thr Glu Cys Ser 210 215 <210> 95 <211 > 216

<212> PRT <213> Homo sapiens <400> 95

Gin Ser Val Leu Thr Gin Pro Pro Ser Glu Ser Val Ser Pro Gly Gin 15 10 15

Thr Ala Ser Val Thr Cys Ser Gly His Lys Leu Gly Asp Lys Tyr Val 20 25 30

Ser Trp Tyr Gin Gin Lys Pro Gly Gin Ser Pro Val Leu Leu Ile Tyr 35 40 45

Gin Asp Asn Arg Arg Pro Ser Gly Ile Pro Glu Arg Phe Ile Gly Ser 50 55 60

Asn Ser Gly Asn Thr Ala Thr Leu Thr Ile Ser Gly Thr Gin Ala Leu 65 70 75 80

Asp Glu Ala Asp Tyr Tyr Cys Gin Ala Trp Asp Ser Ser Thr Ala Val 85 80 95

Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Ala Ala Ala Gly Gin 100 105 110

Pro Lys Ala Ala Pro Ser Val Thr Leu Phe Pro Pro Ser Ser Glu Glu 115 120 125

Leu Gin Ala Asn Lys Ala Thr Leu Val Cys Leu Ile Ser Asp Phe Tyr 130 135 140

Pro Gly Ala Val Thr Val Ala Trp Lys Ala Asp Ser Ser Pro Val Lys 145 150 155 160

Ala Gly Val Glu Thr Thr Thr Pro Ser Lys Gin Ser Asn Asn Lys Tyr 165 170 175

Ala Ala Ser Ser Tyr Leu Ser Leu Thr Pro Glu Gin Trp Lys Ser His 180 185 190

Arg Ser Tyr Ser Cys Gin Val Thr His Glu Gly Ser Thr Val Glu Lys 195 200 205

Thr Val Ala Pro Thr Glu Cys Ser 210 215 <210> 96 <211 > 639

<212> DNA <213> Homo sapiens <220> <221 > CDS <222> (1)..(639) <400> 96 gaa att gtg ctg act cag tct cca ggc acc ctg tct ttg tct cca ggg 48

Glu Ile Val Leu Thr Gin Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly 15 10 15 gaa aga gcc acc ctc tcc tgc agg gcc agt cag cgt gtt age age tac 96

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gin Arg Val Ser Ser Tyr 20 25 30 tta gcc tgg tac caa cag aaa cct ggc cag get ccc agg ctc ctc atc 144

Leu Ala Trp Tyr Gin Gin Lys Pro Gly Gin Ala Pro Arg Leu Leu Ile 35 40 45 tat ggt gea tcc acc agg gcc get ggc atc cca gac agg ttc agt ggc 192

Tyr Gly Ala Ser Thr Arg Ala Ala Gly Ile Pro Asp Arg Phe Ser Gly 50 55 60 agt ggg tct ggg aca gac ttc act ctc acc atc age aga ctg gag cct 240

Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu Pro 65 70 75 80 gaa gat tct gea gtg tat tac tgt cag cag tat ggt agg aca ccg ctc 288

Glu Asp Ser Ala Val Tyr Tyr Cys Gin Gin Tyr Gly Arg Thr Pro Leu 85 90 95 act ttc ggc gga ggg acc aag gtg gag atc aaa cgt gcg gcc gea ccc 336

Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg Ala Ala Ala Pro 100 105 110 age gtg ttc atc ttc ccc ccc tcc gac gag cag ctg aag age ggc acc 384

Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gin Leu Lys Ser Gly Thr 115 120 125 gcc age gtg gtg tgc ctg ctg aac aac ttc tac ccc egg gag gcc aag 432

Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys 130 135 140 gtg cag tgg aag gtg gac aac gcc ctg cag age ggc aac age cag gag 480

Val Gin Trp Lys Val Asp Asn Ala Leu Gin Ser Gly Asn Ser Gin Glu 145 150 155 160 age gtg acc gag cag gac age aag gac tcc acc tac age ctg age age 528

Ser Val Thr Glu Gin Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser 165 170 175 acc ctc acc ctg age aag gcc gac tac gag aag cac aag gtg tac gcc 576

Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala 180 185 190 tgc gag gtg acc cac cag ggc ctg age age ccc gtg acc aag age ttc 624

Cys Glu Val Thr His Gin Gly Leu Ser Ser Pro Val Thr Lys Ser Phe 195 200 205 aac egg ggc gag tgt 639

Asn Arg Gly Glu Cys 210 <210> 97 <211 > 213

<212> PRT <213> Homo sapiens <400> 97

Glu Ile Val Leu Thr Gin Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly 15 10 15

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gin Arg Val Ser Ser Tyr 20 25 30

Leu Ala Trp Tyr Gin Gin Lys Pro Gly Gin Ala Pro Arg Leu Leu Ile 35 40 45

Tyr Gly Ala Ser Thr Arg Ala Ala Gly Ile Pro Asp Arg Phe Ser Gly 50 55 60

Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu Pro 65 70 75 80

Glu Asp Ser Ala Val Tyr Tyr Cys Gin Gin Tyr Gly Arg Thr Pro Leu 85 90 95

Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg Ala Ala Ala Pro 100 105 110

Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gin Leu Lys Ser Gly Thr 115 120 125

Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys 130 135 140

Val Gin Trp Lys Val Asp Asn Ala Leu Gin Ser Gly Asn Ser Gin Glu 145 150 155 160

Ser Val Thr Glu Gin Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser 165 170 175

Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala 180 185 190

Cys Glu Val Thr His Gin Gly Leu Ser Ser Pro Val Thr Lys Ser Phe 195 200 205

Asn Arg Gly Glu Cys 210 <210> 98 <211 > 654

<212> DNA <213> Homo sapiens <220> <221 > CDS <222> (1)..(654) <400> 98 tcc tat gtg ctg act cag cca ccc teg gtg tea gtg gcc cca gga cag 48

Ser Tyr Val Leu Thr Gin Pro Pro Ser Val Ser Val Ala Pro Gly Gin 15 10 15 aeg gcc agg att acc tgt ggg gga aac aac att gga agt aaa agt gtg 96

Thr Ala Arg Ile Thr Cys Gly Gly Asn Asn Ile Gly Ser Lys Ser Val 20 25 30 cae tgg tac cag cag aag cca ggc cag gcc cct gtg ctg gtc gtc tat 144

His Trp Tyr Gin Gin Lys Pro Gly Gin Ala Pro Val Leu Val Val Tyr 35 40 45 gat gat age gac egg ccc tea ggg atc cct gag ega tte tet ggc tcc 192

Asp Asp Ser Asp Arg Pro Ser Gly Ile Pro Glu Arg Phe Ser Gly Ser 50 55 60 aac tet ggg aac aeg gcc acc ctg acc atc age agg gtc gaa gcc ggg 240

Asn Ser Gly Asn Thr Ala Thr Leu Thr Ile Ser Arg Val Glu Ala Gly 65 70 75 80 gat gag gcc gac tat tac tgt cag gtg tgg gat agt agt agt gat cat 288

Asp Glu Ala Asp Tyr Tyr Cys Gin Val Trp Asp Ser Ser Ser Asp His 85 90 95 get gtg tte gga gga ggc acc cag ctg acc gtc etc ggt gcg gcc gea 336

Ala Val Phe Gly Gly Gly Thr Gin Leu Thr Val Leu Gly Ala Ala Ala 100 105 110 ggc cag ccc aag gee get ccc age gtg acc ctg tte ccc ccc tcc tcc 384

Gly Gin Pro Lys Ala Ala Pro Ser Val Thr Leu Phe Pro Pro Ser Ser 115 120 125 gag gag ctg cag gee aac aag gee acc ctg gtg tgc etc atc age gac 432

Glu Glu Leu Gin Ala Asn Lys Ala Thr Leu Val Cys Leu Ile Ser Asp 130 135 140 tte tac cct ggc gcc gtg acc gtg gcc tgg aag gcc gac age age ccc 480

Phe Tyr Pro Gly Ala Val Thr Val Ala Trp Lys Ala Asp Ser Ser Pro 145 150 155 160 gtg aag gcc ggc gtg gag acc acc acc ccc age aag cag age aac aac 528

Val Lys Ala Gly Val Glu Thr Thr Thr Pro Ser Lys Gin Ser Asn Asn 165 170 175 aag tac gee gee age age tac ctg age etc acc ccc gag cag tgg aag 576

Lys Tyr Ala Ala Ser Ser Tyr Leu Ser Leu Thr Pro Glu Gin Trp Lys 180 185 190 age cac egg age tac age tgc cag gtg acc cac gag ggc age acc gtg 624

Ser His Arg Ser Tyr Ser Cys Gin Val Thr His Glu Gly Ser Thr Val 195 200 205 gag aag acc gtg gcc ccc acc gag tgc age 654

Glu Lys Thr Val Ala Pro Thr Glu Cys Ser 210 215 <210> 99 <211 > 218

<212> PRT <213> Homo sapiens <400> 99

Ser Tyr Val Leu Thr Gin Pro Pro Ser Val Ser Val Ala Pro Gly Gin 15 10 15

Thr Ala Arg Ile Thr Cys Gly Gly Asn Asn Ile Gly Ser Lys Ser Val 20 25 30

His Trp Tyr Gin Gin Lys Pro Gly Gin Ala Pro Val Leu Val Val Tyr 35 40 45

Asp Asp Ser Asp Arg Pro Ser Gly Ile Pro Glu Arg Phe Ser Gly Ser 50 55 60

Asn Ser Gly Asn Thr Ala Thr Leu Thr Ile Ser Arg Val Glu Ala Gly 65 70 75 80

Asp Glu Ala Asp Tyr Tyr Cys Gin Val Trp Asp Ser Ser Ser Asp His 85 90 95

Ala Val Phe Gly Gly Gly Thr Gin Leu Thr Val Leu Gly Ala Ala Ala 100 105 110

Gly Gin Pro Lys Ala Ala Pro Ser Val Thr Leu Phe Pro Pro Ser Ser 115 120 125

Glu Glu Leu Gin Ala Asn Lys Ala Thr Leu Val Cys Leu Ile Ser Asp 130 135 140

Phe Tyr Pro Gly Ala Val Thr Val Ala Trp Lys Ala Asp Ser Ser Pro 145 150 155 160

Val Lys Ala Gly Val Glu Thr Thr Thr Pro Ser Lys Gin Ser Asn Asn 165 170 175

Lys Tyr Ala Ala Ser Ser Tyr Leu Ser Leu Thr Pro Glu Gin Trp Lys 180 185 190

Ser His Arg Ser Tyr Ser Cys Gin Val Thr His Glu Gly Ser Thr Val 195 200 205

Glu Lys Thr Val Ala Pro Thr Glu Cys Ser 210 215 <210> 100 <211 > 660

<212> DNA <213> Homo sapiens <220> <221 > CDS <222> (1)..(660) <400> 100 tcc tat gtg ctg act cag cca ccc tea gcg tet ggg acc ccc ggg cag 48

Ser Tyr Val Leu Thr Gin Pro Pro Ser Ala Ser Gly Thr Pro Gly Gin 15 10 15 agg gtc acc ate tet tgt tet gga age age tee aac atc gga agt aat 96

Arg Val Thr Ile Ser Cys Ser Gly Ser Ser Ser Asn Ile Gly Ser Asn 20 25 30 tat gta tac tgg tac cag cag etc cca ggc aeg gee ccc aaa etc etc 144

Tyr Val Tyr Trp Tyr Gin Gin Leu Pro Gly Thr Ala Pro Lys Leu Leu 35 40 45 ate tat agg gat ggt cag egg ccc tea ggg gtc eet gac ega tte tet 192

Ile Tyr Arg Asp Gly Gin Arg Pro Ser Gly Val Pro Asp Arg Phe Ser 50 55 60 ggc tee aag tet ggc acc tea gee tec ctg gee atc agt gga etc egg 240

Gly Ser Lys Ser Gly Thr Ser Ala Ser Leu Ala Ile Ser Gly Leu Arg 65 70 75 80 tee gat gat gag get gat tat tac tgt gea aca tgg gat gac aac ctg 288

Ser Asp Asp Glu Ala Asp Tyr Tyr Cys Ala Thr Trp Asp Asp Asn Leu 85 90 95 agt ggt cca gta tte ggc gga ggg acc aag ctg acc gtc eta ggt gcg 336

Ser Gly Pro Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Ala 100 . 105 110 gee gea ggc cag ccc aag gee get ccc age gtg acc ctg tte ccc ccc 384

Ser Ser Glu Glu Leu Gin Ala Asn Lys Ala Thr Leu Val Cys Leu Ile 130 135 140 age gac tte tac eet ggc gee gtg acc gtg gee tgg aag gcc gac age 480

Asn Asn Lys Tyr Ala Ala Ser Ser Tyr Leu Ser Leu Thr Pro Glu Gin 180 185 190 tgg aag age cac egg age tac age tgc cag gtg acc cae gag ggc age 624

Thr Val Glu Lys Thr Val Ala Pro Thr Glu Cys Ser 210 215 220 <210> 101 <211 > 220

<212> PRT <213> Homo sapiens <400> 101

Ser Tyr Val Leu Thr Gin Pro Pro Ser Ala Ser Gly Thr Pro Gly Gin 15 10 15

Arg Val Thr Ile Ser Cys Ser Gly Ser Ser Ser Asn Ile Gly Ser Asn 20 25 30

Tyr Val Tyr Trp Tyr Gin Gin Leu Pro Gly Thr Ala Pro Lys Leu Leu 35 40 45

Ile Tyr Arg Asp Gly Gin Arg Pro Ser Gly Val Pro Asp Arg Phe Ser 50 55 €0

Gly Ser Lys Ser Gly Thr Ser Ala Ser Leu Ala Ile Ser Gly Leu Arg 65 70 75 80

Ser Asp Asp Glu Ala Asp Tyr Tyr Cys Ala Thr Trp Asp Asp Asn Leu 85 90 95

Ser Gly Pro Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Ala 100 105 110

Ala Ala Gly Gin Pro Lys Ala Ala Pro Ser Val Thr Leu Phe Pro Pro 115 120 125

Ser Ser Glu Glu Leu Gin Ala Asn Lys Ala Thr Leu Val Cys Leu Ile 130 135 140

Ser Asp Phe Tyr Pro Gly Ala Val Thr Val Ala Trp Lys Ala Asp Ser 145 150 155 160

Ser Pro Val Lys Ala Gly Val Glu Thr Thr Thr Pro Ser Lys Gin Ser 165 170 175

Asn Asn Lys Tyr Ala Ala Ser Ser Tyr Leu Ser Leu Thr Pro Glu Gin 180 185 190

Trp Lys Ser His Arg Ser Tyr Ser Cys Gin Val Thr His Glu Gly Ser 195 200 205

Thr Val Glu Lys Thr Val Ala Pro Thr Glu Cys Ser 210 215 220 <210> 102 <211 > 642

<212> DNA <213> Homo sapiens <220> <221 > CDS <222> (1)..(642) <400> 102 gaa att gtg ttg acc cag tct cca ggc acc ctg tct ttg tct cca ggg 48

Glu Ile Val Leu Thr Gin Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly 15 10 15 gaa aga gcc acc ctc tcc tgc agg gcc agt cag agt gtt age age age 96

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gin Ser Val Ser Ser Ser 20 25 30 tac tta gcc tgg tac cag cag aaa cct ggc cag get ccc agg ctc ctc 144

Tyr Leu Ala Trp Tyr Gin Gin Lys Pro Gly Gin Ala Pro Arg Leu Leu 35 40 45 ate tat ggt gea tec age agg gcc act ggc atc cca gac agg ttc agt 192

Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser 50 55 60 ggc agt ggg tct ggg aca gac ttc act ctc acc atc age aga ctg gag 240

Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu 65 70 75 80 cct gaa gat ttt gea gtg tat tac tgt cag cag tat ggt age tea ccc 288

Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gin Gin Tyr Gly Ser Ser Pro 85 90 95 aga act ttc ggc gga ggg acc aag gtg gag atc aaa egt gcg gcc gea 336

Arg Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg Ala Ala Ala 100 105 110 ccc age gtg ttc atc ttc ccc ccc tcc gac gag cag ctg aag age ggc 384

Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gin Leu Lys Ser Gly 115 120 125 acc gcc age gtg gtg tgc ctg ctg aac aac ttc tac ccc egg gag gcc 432

Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala 130 135 140 aag gtg cag tgg aag gtg gac aac gcc ctg cag age ggc aac age cag 480

Lys Val Gin Trp Lys Val Asp Asn Ala Leu Gin Ser Gly Asn Ser Gin 145 150 155 160 gag age gtg acc gag cag gac age aag gac tcc acc tac age ctg age 528

Glu Ser Val Thr Glu Gin Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser 165 170 175 age acc ctc acc ctg age aag gcc gac tac gag aag cac aag gtg tac 576

Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr 180 185 190 gcc tgc gag gtg acc cac cag ggc ctg age age ccc gtg acc aag age 624

Phe Asn Arg Gly Glu Cys 210 <210> 103 <211 > 214 <212> PRT <213> Homo sapiens <400> 103

Glu Ile Val Leu Thr Gin Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly 15 10 15

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gin Ser Val Ser Ser Ser 20 25 30

Tyr Leu Ala Trp Tyr Gin Gin Lys Pro Gly Gin Ala Pro Arg Leu Leu 35 40 45

Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser 50 55 60

Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu 65 70 75 80

Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gin Gin Tyr Gly Ser Ser Pro 85 90 95

Arg Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg Ala Ala Ala 100 105 110

Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gin Leu Lys Ser Gly 115 120 125

Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala 130 135 140

Lys Val Gin Trp Lys Val Asp Asn Ala Leu Gin Ser Gly Asn Ser Gin 145 150 155 160

Glu Ser Val Thr Glu Gin Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser 165 170 175

Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr 180 185 190

Ala Cys Glu Val Thr His Gin Gly Leu Ser Ser Pro Val Thr Lys Ser 195 200 205

Phe Asn Arg Gly Glu Cys 210 <210> 104 <211 > 660

<212> DNA <213> Homo sapiens <220> <221 > CDS <222> (1)..(660) <400> 104 cag tct gcc ctg act cag cct gcc tcc gtg tct ggg tct cct gga cag 48

Gin Ser Ala Leu Thr Gin Pro Ala Ser Val Ser Gly Ser Pro Gly Gin 15 10 15 teg ate ace ate tcc tgc act gga acc age agt gae gtt ggt ggt tat 96

Gin Ala Glu Asp Glu Ala Asp Tyr Tyr Cys Ser Ser Tyr Thr Ser Ser 85 90 95 age act ett gtc ttc gga act ggg acc aag gtc acc gtc eta ggt geg 336

Ser Thr Leu Val Phe Gly Thr Gly Thr Lys Val Thr Val Leu Gly Ala 100 105 110 gcc gca ggc cag ccc aag gcc get ccc age gtg acc ctg ttc ccc ccc 384

Ser Ser Glu Glu Leu Gin Ala Asn Lys Ala Thr Leu Val Cys Leu He 130 135 140 age gac ttc tac cct ggc gcc gtg acc gtg gcc tgg aag gcc gac age 480

Thr Val Glu Lys Thr Val Ala Pro Thr Glu Cys Ser 210 215 220 <210> 105 <211 > 220 <212> PRT <213> Homo sapiens <400>105

Gin Ser Ala Leu Thr Gin Pro Ala Ser Val Ser Gly Ser Pro Gly Gin 15 10 15

Ser Ile Thr Ile Ser Cys Thr Gly Thr Ser Ser Asp Val Gly Gly Tyr 20 25 30

Asn Tyr Val Ser Trp Tyr Gin Gin His Pro Gly Lys Ala Pro Lys Leu 35 40 45

Met Ile Tyr Glu Val Ser Asn Arg Pro Ser Gly Val Ser Asn Arg Phe 50 55 60

Ser Gly Ser Lys Ser Gly Asn Thr Ala Ser Leu Thr lie Ser Gly Leu 65 70 75 80

Gin Ala Glu Asp Glu Ala Asp Tyr Tyr Cys Ser Ser Tyr Thr Ser Ser 85 90 95

Ser Thr Leu Val Phe Gly Thr Gly Thr Lys Val Thr Val Leu Gly Ala 100 105 110

Ala Ala Gly Gin Pro Lys Ala Ala Pro Ser Val Thr Leu Phe Pro Pro 115 120 125

Ser Ser Glu Glu Leu Gin Ala Asn Lys Ala Thr Leu Val Cys Leu lie 130 135 140

Ser Asp Phe Tyr Pro Gly Ala Val Thr Val Ala Trp Lys Ala Asp Ser 145 150 155 160

Ser Pro Val Lys Ala Gly Val Glu Thr Thr Thr Pro Ser Lys Gin Ser 165 170 175

Asn Asn Lys Tyr Ala Ala Ser Ser Tyr Leu Ser Leu Thr Pro Glu Gin 180 185 190

Trp Lys Ser His Arg Ser Tyr Ser Cys Gin Val Thr His Glu Gly Ser 195 200 205

Thr Val Glu Lys Thr Val Ala Pro Thr Glu Cys Ser 210 215 220 <210> 106 <211 > 654

<212> DNA <213> Homo sapiens <220> <221 > CDS <222> (1)..(654) <400> 106 cag tct gtc gtg acg cag ccg ccc teg gtg tea gtg gee cca gga cag 48

Gin Ser Val Val Thr Gin Pro Pro Ser Val Ser Val Ala Pro Gly Gin 15 10 15 acg gee agg att ace tgt ggg gga aac aac att gga agt aaa agt gtg 96

Thr Ala Arg Ile Thr Cys Gly Gly Asn Asn Ile Gly Ser Lys Ser Val 20 25 30 cac tgg tac cag cag aag cca ggc cag gee cct gtg ctg gtc gtc tat 144

His Trp Tyr Gin Gin Lys Pro Gly Gin Ala Pro Val Leu Val Val Tyr 35 40 45 gat gat age gac egg ccc tea ggg ate cct gag ega ttc tct ggc tee 192

Asp Asp Ser Asp Arg Pro Ser Gly lie Pro Glu Arg Phe Ser Gly Ser 50 55 60 aac tct ggg aac acg gee acc ctg acc ate age agg gtc gaa gee ggg 240

Asn Ser Gly Asn Thr Ala Thr Leu Thr lie Ser Arg Val Glu Ala Gly 65 70 75 80 gat gag gee gac tat tac tgt cag gtg tgg gat agt agt agt gat cat 288

Asp Glu Ala Asp Tyr Tyr Cys Gin Val Trp Asp Ser Ser Ser Asp His 85 90 95 tat gtc ttc gga act ggg acc aag gtc acc gtc eta ggt geg gee gca 336

Tyr Val Phe Gly Thr Gly Thr Lys Val Thr Val Leu Gly Ala Ala Ala 100 105 110 ggc cag ccc aag gee get ccc age gtg acc ctg ttc ccc ccc tee tee 384

Gly Gin Pro Lys Ala Ala Pro Ser Val Thr Leu Phe Pro Pro Ser Ser 115 120 125 gag gag ctg cag gee aac aag gee acc ctg gtg tgc etc ate age gac 432

Glu Glu Leu Gin Ala Asn Lys Ala Thr Leu Val Cys Leu lie Ser Asp 130 135 140 ttc tac cct ggc gee gtg acc gtg gee tgg aag gee gac age age ccc 480

Phe Tyr Pro Gly Ala Val Thr Val Ala Trp Lys Ala Asp Ser Ser Pro 145 150 155 160 gtg aag gee ggc gtg gag acc acc acc ccc age aag cag age aac aac 528

Ser His Arg Ser Tyr Ser Cys Gin Val Thr His Glu Gly Ser Thr Val 195 200 205 gag aag acc gtg gee ccc acc gag tgc age 654

Glu Lys Thr Val Ala Pro Thr Glu Cys Ser 210 215 <210> 107 <211> 218 <212> PRT <213> Homo sapiens <400> 107

Gin Ser Val Val Thr Gin Pro Pro Ser Val Ser Val Ala Pro Gly Gin 15 10 15

Thr Ala Arg Ile Thr Cys Gly Gly Asn Asn Ile Gly Ser Lys Ser Val 20 25 30

His Trp Tyr Gin Gin Lys Pro Gly Gin Ala Pro Val Leu Val Val Tyr 35 40 45

Asp Asp Ser Asp Arg Pro Ser Gly Ile Pro Glu Arg Phe Ser Gly Ser 50 55 60

Asn Ser Gly Asn Thr Ala Thr Leu Thr Ile Ser Arg Val Glu Ala Gly 65 70 75 80

Asp Glu Ala Asp Tyr Tyr Cys Gin Val Trp Asp Ser Ser Ser Asp His 85 90 95

Tyr Val Phe Gly Thr Gly Thr Lys Val Thr Val Leu Gly Ala Ala Ala 100 105 110

Gly Gin Pro Lys Ala Ala Pro Ser Val Thr Leu Phe Pro Pro Ser Ser 115 120 125

Glu Glu Leu Gin Ala Asn Lys Ala Thr Leu Val Cys Leu Ile Ser Asp 130 135 140

Phe Tyr Pro Gly Ala Val Thr Val Ala Trp Lys Ala Asp Ser Ser Pro 145 150 155 160

Val Lys Ala Gly Val Glu Thr Thr Thr Pro Ser Lys Gin Ser Asn Asn 165 170 175

Lys Tyr Ala Ala Ser Ser Tyr Leu Ser Leu Thr Pro Glu Gin Trp Lys 180 185 190

Ser His Arg Ser Tyr Ser Cys Gin Val Thr His Glu Gly Ser Thr Val 195 200 205

Glu Lys Thr Val Ala Pro Thr Glu Cys Ser 210 215 <210> 108 <211 > 660

<212> DNA <213> Homo sapiens <220> <221 > CDS <222> (1)..(660) <400> 108 act gtg ttg aca cag ccg ccc tea gtg tet ggg gee cca ggg cag agg 48

Thr Val Leu Thr Gin Pro Pro Ser Val Ser Gly Ala Pro Gly Gin Arg 15 10 15 gtc ace ate tee tgc act ggg age age tee aac ate ggg gca ggt tat 96

Val Thr Ile Ser Cys Thr Gly Ser Ser Ser Asn Ile Gly Ala Gly Tyr 20 25 30 gat gta cac tgg tac cag cag ett cca gga aca gee ccc aaa etc etc 144

Asp Val His Trp Tyr Gin Gin Leu Pro Gly Thr Ala Pro Lys Leu Leu 35 40 45 ate tat ggt aac age aat egg ccc tea ggg gtc cct gac ega ttc tet 192 lie Tyr Gly Asn Ser Asn Arg Pro Ser Gly Val Pro Asp Arg Phe Ser 50 55 60 ggc tee aag tet ggc aeg tea gee ace ctg ggc ate ace gga etc cag 240

Gly Ser Lys Ser Gly Thr Ser Ala Thr Leu Gly lie Thr Gly Leu Gin 65 70 75 80 act ggg gac gag gee gat tat tac tgc gga aca tgg gat age age ctg 288

Thr Gly Asp Glu Ala Asp Tyr Tyr Cys Gly Thr Trp Asp Ser Ser Leu 85 90 95 agt get tat gtc ttc gga act ggg acc aag gtc acc gtc eta ggt geg 336

Ser Ala Tyr Val Phe Gly Thr Gly Thr Lys Val Thr Val Leu Gly Ala 100 105 110 gee gca ggc cag ccc aag gee get ccc age gtg acc ctg ttc ccc ccc 384

Ala Ala Gly Gin Pro Lys Ala Ala Pro Ser Val Thr Leu Phe Pro Pro 115 120 125 tee tee gag gag ctg cag gee aac aag gee acc ctg gtg tgc etc ate 432

Trp Lys Ser His Arg Ser Tyr Ser Cys Gin Val Thr His Glu Gly Ser 195 200 205 acc gtg gag aag acc gtg gee ccc acc gag tgc age 660

Thr Val Glu Lys Thr Val Ala Pro Thr Glu Cys Ser 210 215 220 <210> 109 <211 > 220 <212> PRT <213> Homo sapiens <400> 109

Thr Val Leu Thr Gin Pro Pro Ser Val Ser Gly Ala Pro Gly Gin Arg 15 10 15

Val Thr Ile Ser Cys Thr Gly Ser Ser Ser Asn Ile Gly Ala Gly Tyr 20 25 30

Asp Val His Trp Tyr Gin Gin Leu Pro Gly Thr Ala Pro Lys Leu Leu 35 40 45

Ile Tyr Gly Asn Ser Asn Arg Pro Ser Gly Val Pro Asp Arg Phe Ser 50 55 60

Gly Ser Lys Ser Gly Thr Ser Ala Thr Leu Gly Ile Thr Gly Leu Gin 65 70 75 80

Thr Gly Asp Glu Ala Asp Tyr Tyr Cys Gly Thr Trp Asp Ser Ser Leu 85 90 95

Ser Ala Tyr Val Phe Gly Thr Gly Thr Lys Val Thr Val Leu Gly Ala 100 105 110

Ala Ala Gly Gin Pro Lys Ala Ala Pro Ser Val Thr Leu Phe Pro Pro 115 120 125

Ser Ser Glu Glu Leu Gin Ala Asn Lys Ala Thr Leu Val Cys Leu Ile 130 135 140

Ser Asp Phe Tyr Pro Gly Ala Val Thr Val Ala Trp Lys Ala Asp Ser 145 150 155 160

Ser Pro Val Lys Ala Gly Val Glu Thr Thr Thr Pro Ser Lys Gin Ser 165 170 175

Asn Asn Lys Tyr Ala Ala Ser Ser Tyr Leu Ser Leu Thr Pro Glu Gin 180 185 190

Trp Lys Ser His Arg Ser Tyr Ser Cys Gin Val Thr His Glu Gly Ser 195 200 205

Thr Val Glu Lys Thr Val Ala Pro Thr Glu Cys Ser 210 215 220

<210> 110 <211> 565 <212> PRT <213> Influenza A virus <220> <221 > MISC_FEATURE <222> (1)..(565) <223> HA protein of influenza virus H5N1 isolate AA/ietnam/1203/2004 <400> 110

Met Glu Lys Ile Val Leu Leu Phe Ala Ile Val Ser Leu Val Lys Ser 15 10 15

Asp Gin Ile Cys Ile Gly Tyr His Ala Asn Asn Ser Thr Glu Gin Val 20 25 30

Asp Thr Ile Met Glu Lys Asn Val Thr Val Thr His Ala Gin Asp Ile 35 40 45

Leu Glu Lys Lys His Asn Gly Lys Leu Cys Asp Leu Asp Gly Val Lys 50 55 60

Pro Leu Ile Leu Arg Asp Cys Ser Val Ala Gly Trp Leu Leu Gly Asn 65 70 75 80

Pro Met Cys Asp Glu Phe Ile Asn Val Pro Glu Trp Ser Tyr Ile Val 85 90 95

Glu Lys Ala Asn Pro Val Asn Asp Leu Cys Tyr Pro Gly Asp Phe Asn 100 105 110

Asp Tyr Glu Glu Leu Lys His Leu Leu Ser Arg Ile Asn His Phe Glu 115 120 125

Lys Ile Gin Ile Ile Pro Lys Ser Ser Trp Ser Ser His Glu Ala Ser 130 135 140

Leu Gly Val Ser Ser Ala Cys Pro Tyr Gin Gly Lys Ser Ser Phe Phe 145 150 155 160

Arg Asn Val Val Trp Leu Ile Lys Lys Asn Ser Thr Tyr Pro Thr Ile 165 170 175

Lys Arg Ser Tyr Asn Asn Thr Asn Gin Glu Asp Leu Leu Val Leu Trp 180 185 190

Gly Ile His His Pro Asn Asp Ala Ala Glu Gin Thr Lys Leu Tyr Gin 195 200 205

Asn Pro Thr Thr Tyr Ile Ser Val Gly Thr Ser Thr Leu Asn Gin Arg 210 215 220

Leu Val Pro Arg Ile Ala Thr Arg Ser Lys Val Asn Gly Gin Ser Gly 225 230 235 240

Arg Met Glu Phe Phe Trp Thr Ile Leu Lys Pro Asn Asp Ala Ile Asn 245 250 255

Phe Glu Ser Asn Gly Asn Phe Ile Ala Pro Glu Tyr Ala Tyr Lys Ile 260 265 270

Val Lys Lys Gly Asp Ser Thr Ile Met Lys Ser Glu Leu Glu Tyr Gly 275 280 285

Asn Cys Asn Thr Lys Cys Gin Thr Pro Met Gly Ala Ile Asn Ser Ser 290 295 300

Met Pro Phe His Asn Ile His Pro Leu Thr Ile Gly Glu Cys Pro Lys 305 310 315 320

Tyr Val Lys Ser Asn Arg Leu Val Leu Ala Thr Gly Leu Arg Asn Ser 325 330 335

Pro Gin Arg Glu Arg Arg Arg Lys Lys Arg Gly Leu Phe Gly Ala Ile 340 345 350

Ala Gly Phe Ile Glu Gly Gly Trp Gin Gly Met Val Asp Gly Trp Tyr 355 360 365

Gly Tyr His His Ser Asn Glu Gin Gly Ser Gly Tyr Ala Ala Asp Lys 370 375 380

Glu Ser Thr Gin Lys Ala Ile Asp Gly Val Thr Asn Lys Val Asn Ser 385 390 395 400

Ile Ile Asp Lys Met Asn Thr Gin Phe Glu Ala Val Gly Arg Glu Phe 405 410 415

Asn Asn Leu Glu Arg Arg Ile Glu Asn Leu Asn Lys Lys Met Glu Asp 420 425 430

Gly Phe Leu Asp Val Trp Thr Tyr Asn Ala Glu Leu Leu Val Leu Met 435 440 445

Glu Asn Glu Arg Thr Leu Asp Phe His Asp Ser Asn Val Lys Asn Leu 450 455 460

Tyr Asp Lys Val Arg Leu Gin Leu Arg Asp Asn Ala Lys Glu Leu Gly 465 470 475 480

Asn Gly Cys Phe Glu Phe Tyr His Lys Cys Asp Asn Glu Cys Met Glu 485 490 495

Ser Val Arg Asn Gly Thr Tyr Asp Tyr Pro Gin Tyr Ser Glu Glu Ala 500 505 510

Arg Leu Lys Arg Glu Glu Ile Ser Gly Val Lys Leu Glu Ser Ile Gly 515 520 525

Ile Tyr Gin Ile Leu Ser Ile Tyr Ser Thr Val Ala Ser Ser Leu Ala 530 535 540

Leu Ala Ile Met Val Ala Gly Leu Ser Leu Trp Met Cys Ser Asn Gly 545 550 555 560

Ser Leu Gin Cys Arg 565 <210 111 <211> 565

<212> PRT <213> Influenza A virus <220>

<221 > MISC_FEATURE <223> HA protein of influenza virus H5N1 isolate A/Vietnam/1194/2004 (H5N1TV) <400> 111

Met Glu Lys Ile Val Leu Leu Phe Ala Ile Val Ser Leu Val Lys Ser 15 10 15

Asp Gin Ile Cys Ile Gly Tyr His Ala Asn Asn Ser Thr Glu Gin Val 20 25 30

Asp Thr Ile Met Glu Lys Asn Val Thr Val Thr His Ala Gin Asp Ile 35 40 45

Leu Glu Lys Thr His Asn Gly Lys Leu Cys Asp Leu Asp Gly Val Lys 50 55 60

Pro Leu Ile Leu Arg Asp Cys Ser Val Ala Gly Trp Leu Leu Gly Asn 65 70 75 80

Pro Met Cys Asp Glu Phe Ile Asn Val Pro Glu Trp Ser Tyr Ile Val 85 90 95

Glu Lys Ala Asn Pro Val Asn Asp Leu Cys Tyr Pro Gly Asp Phe Asn 100 105 110

Asp Tyr Glu Glu Leu Lys His Leu Leu Ser Arg ile Asn His Phe Glu 115 120 125

Lys Ile Gin Ile Ile Pro Lys Ser Ser Trp Ser Ser His Glu Ala Ser 130 135 140

Leu Gly Val Ser Ser Ala Cys Pro Tyr Gin Gly Lys Ser Ser Phe Phe 145 150 155 160

Arg Asn Val Val Trp Leu Ile Lys Lys Asn Ser Thr Tyr Pro Thr Ile 165 170 175

Lys Arg Ser Tyr Asn Asn Thr Asn Gin Glu Asp Leu Leu Val Leu Trp 180 185 190

Gly Ile His His Pro Asn Asp Ala Ala Glu Gin Thr Lys Leu Tyr Gin 195 200 205

Asn Pro Thr Thr Tyr Ile Ser Val Gly Thr Ser Thr Leu Asn Gin Arg 210 215 220

Leu Val Pro Arg Ile Ala Thr Arg Ser Lys Val Asn Gly Gin Ser Gly 225 230 235 240

Arg Met Glu Phe Phe Trp Thr Ile Leu Lys Pro Asn Asp Ala Ile Asn 245 250 255

Phe Glu Ser Asn Gly Asn Phe Ile Ala Pro Glu Tyr Ala Tyr Lys Ile 260 265 270

Val Lys Lys Gly Asp Ser Thr Ile Met Lys Ser Glu Leu Glu Tyr Gly 275 280 285

Asn Cys Asn Thr Lys Cys Gin Thr Pro Met Gly Ala Ile Asn Ser Ser 290 295 300

Met Pro Phe His Asn Ile His Pro Leu Thr Ile Gly Glu Cys Pro Lys 305 310 315 320

Tyr Val Lys Ser Asn Arg Leu Val Leu Ala Thr Gly Leu Arg Asn Ser 325 330 335

Pro Gin Arg Glu Arg Arg Arg Lys Lys Arg Gly Leu Phe Gly Ala Ile 340 345 350

Ala Gly Phe He Glu Gly Gly Trp Gin Gly Met Val Asp Gly Trp Tyr 355 360 365

Gly Tyr Hie His Ser Asn Glu Gin Gly Ser Gly Tyr Ala Ala Asp Lys 370 375 380

Glu Ser Thr Gin Lys Ala Ile Asp Gly Val Thr Asn Lys Val Asn Ser 385 390 395 400 lie He Asp Lys Met Asn Thr Gin Phe Glu Ala Val Gly Arg Glu Phe 405 410 415

Asn Asn Leu Glu Arg Arg He Glu Asn Leu Asn Lys Lys Met Glu Asp 420 425 430

Gly Phe Leu Asp Val Trp Thr Tyr Asn Ala Glu Leu Leu Val Leu Met 435 440 445

Glu Asn Glu Arg Thr Leu Asp Phe His Asp Ser Asn Val Lys Asn Leu 450 455 460

Tyr Asp Lys Val Arg Leu Gin Leu Arg Asp Asn Ala Lys Glu Leu Gly 465 470 475 480

Asn Gly Cys Phe Glu Phe Tyr His Lys Cys Asp Asn Glu Cys Met Glu 485 490 495

Ser Val Arg Asn Gly Thr Tyr Asp Tyr Pro Gin Tyr Ser Glu Glu Ala 500 505 510

Arg Leu Lys Arg Glu Glu He Ser Gly Val Lys Leu Glu Ser He Gly 515 520 525

He Tyr Gin lie Leu Ser lie Tyr Ser Thr Val Ala Ser Ser Leu Ala 530 535 540

Leu Ala He Met Val Ala Gly Leu Ser Leu Trp Met Cys Ser Asn Gly 545 550 555 560

Ser Leu Gin Cys Arg 565

<210> 112 <211> 565 <212> PRT <213> Influenza A virus <220

<221 > MISC_FEATURE <223> Consensus amino acid sequence representing HAs from strains isolated in Indonesia and China (H5N1IC) <400 112

Met Glu Lys Ile Val Leu Leu Leu Ala Ile Val Ser Leu Val Lys Ser 15 10 15

Asp Gin Ile Cys Ile Gly Tyr His Ala Asn Asn Ser Thr Glu Gin Val 20 25 30

Asp Thr Ile Met Glu Lys Asn Val Thr Val Thr His Ala Gin Asp Ile 35 40 45

Leu Glu Lys Thr His Asn Gly Lys Leu Cys Asp Leu Asp Gly Val Lys 50 55 60

Pro Leu Ile Leu Arg Asp Cys Ser Val Ala Gly Trp Leu Leu Gly Asn 65 70 75 80

Pro Met Cys Asp Glu Phe Ile Asn Val Pro Glu Trp Ser Tyr Ile Val 85 90 95

Glu Lys Ala Asn Pro Ala Asn Asp Leu Cys Tyr Pro Gly Asn Phe Asn 100 105 110

Asp Tyr Glu Glu Leu Lys His Leu Leu Ser Arg Ile Asn His Phe Glu 115 120 125

Lys Ile Gin Ile Ile Pro Lys Ser Ser Trp Ser Asp His Glu Ala Ser 130 135 140

Ser Gly Val Ser Ser Ala Cys Pro Tyr Gin Gly Lys Ser Ser Phe Phe 145 150 155 160

Arg Asn Val Val Trp Leu Ile Lys Lys Asn Ser Ser Tyr Pro Thr Ile 165 170 175

Lys Arg Ser Tyr Asn Asn Thr Asn Gin Glu Asp Leu Leu Val Leu Trp 180 185 190

Gly Ile His His Pro Asn Asp Ala Ala Glu Gin Thr Arg Leu Tyr Gin 195 200 205

Asn Pro Thr Thr Tyr Ile Ser Val Gly Thr Ser Thr Leu Asn Gin Arg 210 215 220

Leu Val Pro Lys Ile Ala Thr Arg Ser Lys Val Asn Gly Gin Ser Gly 225 230 235 240

Arg Met Glu Phe Phe Trp Thr He Leu Lys Pro Asn Asp Ala lie Asn 245 250 255

Phe Glu Ser Asn Gly Asn Phe lie Ala Pro Glu Tyr Ala Tyr Lys lie 260 265 270

Val Lys Lys Gly Asp Ser Ala lie Met Lys Ser Glu Leu Glu Tyr Gly 275 280 285

Asn Cys Asn Thr Lys Cys Gin Thr Pro Met Gly Ala lie Asn Ser Ser 290 295 300

Met Pro Phe His Asn lie His Pro Leu Thr lie Gly Glu Cys Pro Lys 305 310 315 320

Tyr Val Lys Ser Asn Arg Leu Val Leu Ala Thr Gly Leu Arg Asn Ser 325 330 335

Pro Gin Arg Glu Arg Arg Arg Lys Lys Arg Gly Leu Phe Gly Ala lie 340 345 350

Ala Gly Phe lie Glu Gly Gly Trp Gin Gly Met Val Asp Gly Trp Tyr 355 360 365

Gly Tyr His His Ser Asn Glu Gin Gly Ser Gly Tyr Ala Ala Asp Lys 370 375 380

Glu Ser Thr Gin Lys Ala lie Asp Gly Val Thr Asn Lys Val Asn Ser 385 390 395 400 lie lie Asp Lys Met Asn Thr Gin Phe Glu Ala Val Gly Arg Glu Phe 405 410 415

Asn Asn Leu Glu Arg Arg lie Glu Asn Leu Asn Lys Lys Met Glu Asp 420 425 430

Gly Phe Leu Asp Val Trp Thr Tyr Asn Ala Glu Leu Leu Val Leu Met 435 440 445

Glu Asn Glu Arg Thr Leu Asp Phe His Asp Ser Asn Val Lys Asn Leu 450 455 460

Tyr Asp Lys Val Arg Leu Gin Leu Arg Asp Asn Ala Lys Glu Leu Gly 465 470 475 480

Asn Gly Cys Phe Glu Phe Tyr His Lys Cys Asp Asn Glu Cys Met Glu 485 490 495

Ser Val Arg Asn Gly Thr Tyr Asp Tyr Pro Gin Tyr Ser Glu Glu Ala 500 505 510

Arg Leu Lys Arg Glu Glu lie Ser Gly Val Lys Leu Glu Ser lie Gly 515 520 525 lie Tyr Gin lie Leu Ser lie Tyr Ser Thr Val Ala Ser Ser Leu Ala 530 535 540

Leu Ala He Met Val Ala Gly Leu Ser Leu Trp Met Cys Ser Asn Gly 545 550 555 560

Ser Leu Gin Cys Arg 565

<210> 113 <211> 567 <212> PRT <213> Influenza A virus <220>

<221 > MISC_FEATURE

<223> Soluble part of HA from H5N1TV <220> <221 > MISC_FEATURE <222> (533)..(546) <223> Spacer <220> <221 > MISC_FEATURE <222> (547)..(556) <223> Myc-tag <220> <221 > MISC_FEATURE <222> (557)..(561) <223> Spacer <220> <221 > MISC_FEATURE <222> (562)..(567) <223> His-tag <400> 113

Met Glu Lys Ile Val Leu Leu Phe Ala Ile Val Ser Leu Val Lys Ser 15 10 15

Asp Gin Ile Cys Ile Gly Tyr His Ala Asn Asn Ser Thr Glu Gin Val 20 25 30

Asp Thr Ile Met Glu Lys Asn Val Thr Val Thr His Ala Gin Asp Ile 35 40 45

Leu Glu Lys Thr His Asn Gly Lys Leu Cys Asp Leu Asp Gly Val Lys 50 55 60

Pro Leu Ile Leu Arg Asp Cys Ser Val Ala Gly Trp Leu Leu Gly Asn 65 70 75 80

Pro Met Cys Asp Glu Phe lie Asn Val Pro Glu Trp Ser Tyr lie Val 85 90 95

Glu Lys Ala Asn Pro Val Asn Asp Leu Cys Tyr Pro Gly Asp Phe Asn 100 105 110

Asp Tyr Glu Glu Leu Lys His Leu Leu Ser Arg lie Asn His Phe Glu 115 120 125

Lys lie Gin lie lie Pro Lys Ser Ser Trp Ser Ser His Glu Ala Ser 130 135 140

Leu Gly Val Ser Ser Ala Cys Pro Tyr Gin Gly Lys Ser Ser Phe Phe 145 150 155 160

Arg Asn Val Val Trp Leu lie Lys Lys Asn Ser Thr Tyr Pro Thr lie 165 170 175

Lys Arg Ser Tyr Asn Asn Thr Asn Gin Glu Asp Leu Leu Val Leu Trp 180 185 190

Gly lie His His Pro Asn Asp Ala Ala Glu Gin Thr Lys Leu Tyr Gin 195 200 205

Asn Pro Thr Thr Tyr lie Ser Val Gly Thr Ser Thr Leu Asn Gin Arg 210 215 220

Leu Val Pro Arg lie Ala Thr Arg Ser Lys Val Asn Gly Gin Ser Gly 225 230 235 240

Arg Met Glu Phe Phe Trp Thr lie Leu Lys Pro Asn Asp Ala lie Asn 245 250 255

Phe Glu Ser Asn Gly Asn Phe lie Ala Pro Glu Tyr Ala Tyr Lys lie 260 265 270

Val Lys Lys Gly Asp Ser Thr lie Met Lys Ser Glu Leu Glu Tyr Gly 275 280 285

Asn Cys Asn Thr Lys Cys Gin Thr Pro Met Gly Ala lie Asn Ser Ser 290 295 300

Met Pro Phe His Asn lie His Pro Leu Thr lie Gly Glu Cys Pro Lys 305 310 315 320

Tyr Val Lys Ser Asn Arg Leu Val Leu Ala Thr Gly Leu Arg Asn Ser 325 330 335

Pro Gin Arg Glu Arg Arg Arg Lys Lys Arg Gly Leu Phe Gly Ala Ile 340 345 350

Ala Gly Phe Ile Glu Gly Gly Trp Gin Gly Met Val Asp Gly Trp Tyr 355 360 365

Gly Tyr His His Ser Asn Glu Gin Gly Ser Gly Tyr Ala Ala Asp Lys 370 375 380

Glu Ser Thr Gin Lys Ala Ile Asp Gly Val Thr Asn Lys Val Asn Ser 385 390 395 400

Ile Ile Asp Lys Met Asn Thr Gin Phe Glu Ala Val Gly Arg Glu Phe 405 410 415

Asn Asn Leu Glu Arg Arg Ile Glu Asn Leu Asn Lys Lys Met Glu Asp 420 425 430

Gly Phe Leu Asp Val Trp Thr Tyr Asn Ala Glu Leu Leu Val Leu Met 435 440 445

Glu Asn Glu Arg Thr Leu Asp Phe His Asp Ser Asn Val Lys Asn Leu 450 455 460

Tyr Asp Lys Val Arg Leu Gin Leu Arg Asp Asn Ala Lys Glu Leu Gly 465 470 475 480

Asn Gly Cys Phe Glu Phe Tyr His Lys Cys Asp Asn Glu Cys Met Glu 485 490 495

Ser Val Arg Asn Gly Thr Tyr Asp Tyr Pro Gin Tyr Ser Glu Glu Ala 500 505 510

Arg Leu Lys Arg Glu Glu Ile Ser Gly Val Lys Leu Glu Ser Ile Gly 515 520 525

Ile Tyr Gin Ile Gin His Ser Gly Gly Arg Ser Ser Leu Glu Gly Pro 530 535 540

Arg Phe Glu Gin Lys Leu Ile Ser Glu Glu Asp Leu Asn Met His Thr 545 550 555 560

Gly His His His His His His 565

<210> 114 <211> 567 <212> PRT <213> Influenza A virus <220>

<221 > MISC_FEATURE

<223> Soluble part of HA from H5N1 IC <220> <221 > MISC_FEATURE <222> (533)..(546) <223> Spacer <220> <221 > MISC_FEATURE <222> (547)..(556) <223> Myc-tag <220> <221 > MISC_FEATURE <222> (557)..(561) <223> Spacer <220> <221 > MISC_FEATURE <222> (562)..(567) <223> His-tag <400> 114

Met Glu Lys Ile Val Leu Leu Leu Ala Ile Val Ser Leu Val Lys Ser 15 10 15

Asp Gin Ile Cys Ile Gly Tyr His Ala Asn Asn Ser Thr Glu Gin Val 20 25 30

Asp Thr Ile Met Glu Lys Asn Val Thr Val Thr His Ala Gin Asp Ile 35 40 45

Leu Glu Lys Thr His Asn Gly Lys Leu Cys Asp Leu Asp Gly Val Lys 50 55 60

Pro Leu Ile Leu Arg Asp Cys Ser Val Ala Gly Trp Leu Leu Gly Asn 65 70 75 80

Pro Met Cys Asp Glu Phe Ile Asn Val Pro Glu Trp Ser Tyr Ile Val 85 90 95

Glu Lys Ala Asn Pro Ala Asn Asp Leu Cys Tyr Pro Gly Asn Phe Asn 100 105 110

Asp Tyr Glu Glu Leu Lys His Leu Leu Ser Arg Ile Asn His Phe Glu 115 120 125

Lys Ile Gin Ile Ile Pro Lys Ser Ser Trp Ser Asp His Glu Ala Ser 130 135 140

Ser Gly Val Ser Ser Ala Cys Pro Tyr Gin Gly Lys Ser Ser Phe Phe 145 150 155 160

Arg Asn Val Val Trp Leu Ile Lys Lys Asn Ser Ser Tyr Pro Thr Ile 165 170 175

Lys Arg Ser Tyr Asn Asn Thr Asn Gin Glu Asp Leu Leu Val Leu Trp 180 185 190

Gly Ile His His Pro Asn Asp Ala Ala Glu Gin Thr Arg Leu Tyr Gin 195 200 205

Asn Pro Thr Thr Tyr Ile Ser Val Gly Thr Ser Thr Leu Asn Gin Arg 210 215 220

Leu Val Pro Lys Ile Ala Thr Arg Ser Lys Val Asn Gly Gin Ser Gly 225 230 235 240

Arg Met Glu Phe Phe Trp Thr Ile Leu Lys Pro Asn Asp Ala Ile Asn 245 250 255

Phe Glu Ser Asn Gly Asn Phe Ile Ala Pro Glu Tyr Ala Tyr Lys Ile 260 265 270

Val Lys Lys Gly Asp Ser Ala Ile Met Lys Ser Glu Leu Glu Tyr Gly 275 280 285

Asn Cys Asn Thr Lys Cys Gin Thr Pro Met Gly Ala Ile Asn Sex Ser 290 295 300

Met Pro Phe His Asn Ile His Pro Leu Thr Ile Gly Glu Cys Pro Lys 305 310 315 320

Tyr Val Lys Ser Asn Arg Leu Val Leu Ala Thr Gly Leu Arg Asn Ser 325 330 335

Pro Gin Arg Glu Arg Arg Arg Lys Lys Arg Gly Leu Phe Gly Ala Ile 340 345 350

Ala Gly Phe Ile Glu Gly Gly Trp Gin Gly Met Val Asp Gly Trp Tyr 355 360 365

Gly Tyr His His Ser Asn Glu Gin Gly Ser Gly Tyr Ala Ala Asp Lys 370 375 380

Glu Ser Thr Gin Lys Ala Ile Asp Gly Val Thr Asn Lys Val Asn Ser 385 390 395 400

Ile Ile Asp Lys Met Asn Thr Gin Phe Glu Ala Val Gly Arg Glu Phe 405 410 415

Asn Asn Leu Glu Arg Arg Ile Glu Asn Leu Asn Lys Lys Met Glu Asp 420 425 430

Gly Phe Leu Asp Val Trp Thr Tyr Asn Ala Glu Leu Leu Val Leu Met 435 440 445

Glu Asn Glu Arg Thr Leu Asp Phe His Asp Ser Asn Val Lys Asn Leu 450 455 460

Tyr Asp Lys Val Arg Leu Gin Leu Arg Asp Asn Ala Lys Glu Leu Gly 465 470 475 480

Asn Gly Cys Phe Glu Phe Tyr His Lys Cys Asp Asn Glu Cys Met Glu 485 490 495

Ser Val Arg Asn Gly Thr Tyr Asp Tyr Pro Gin Tyr Ser Glu Glu Ala 500 505 510

Arg Leu Lys Arg Glu Glu Ile Ser Gly Val Lys Leu Glu Ser Ile Gly 515 520 525

Ile Tyr Gin Ile Gin His Ser Gly Gly Arg Ser Ser Leu Glu Gly Pro 530 535 540

Arg Phe Glu Gin Lys Leu Ile Ser Glu Glu Asp Leu Asn Met His Thr 545 550 555 560

Gly His His His His His His 565 <210> 115 <211> 744 <212> DNA <213> Artificial <220> <223> SC06-255 <220> <221 > CDS <222> (1)..(744) <400> 115 gag gtg cag ctg gtg gag tct ggg get gag gtg aag aag cct ggg tcc 48

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Pro Phe Arg Ser Tyr 20 25 30 get ate age tgg gtg ega cag gee eet gga caa ggg cct gag tgg atg 144

Ala Ile Ser Trp Val Arg Gin Ala Pro Gly Gin Gly Pro Glu Trp Met 35 40 45 gga ggg ate ate eet att ttt ggt aca aoa aaa tac gca ccg aag ttc 192

Gin Gly Arg Val Thr Ile Thr Ala Asp Asp Phe Ala Gly Thr Val Tyr 65 70 75 80 atg gag ctg age age ctg ega tet gag gac aeg gee atg tac tac tgt 288

Ala Lys His Met Gly Tyr Gin Val Arg Glu Thr Met Asp Val Trp Gly 100 105 110 aaa ggg acc aeg gtc acc gtc teg age ggt aeg ggc ggt tea ggc gga 384

Lys Gly Thr Thr Val Thr Val Ser Ser Gly Thr Gly Gly Ser Gly Gly 115 120 125 acc ggc age ggc act ggc ggg teg aeg tee tat gtg ctg act cag cca 432

Thr Gly Ser Gly Thr Gly Gly Ser Thr Ser Tyr Val Leu Thr Gin Pro 130 135 140 ccc tea geg tet ggg acc ccc ggg cag agg gtc acc ate tet tgt tet 480

Pro Ser Ala Ser Gly Thr Pro Gly Gin Arg Val Thr lie Ser Cys Ser 145 150 155 160 gga age aeg ttc aac ate gga agt aat get gta gac tgg tac egg cag 528

Gly Ser Thr Phe Asn lie Gly Ser Asn Ala Val Asp Trp Tyr Arg Gin 165 170 175 etc cca gga aeg gee ccc aaa etc etc ate tat agt aat aat cag egg 576

Leu Pro Gly Thr Ala Pro Lys Leu Leu lie Tyr Ser Asn Asn Gin Arg 180 185 190 ccc tea ggg gtc cct gac ega ttc tet ggc tee agg tet ggc acc tea 624

Pro Ser Gly Val Pro Asp Arg Phe Ser Gly Ser Arg Ser Gly Thr Ser 195 200 205 gee tee ctg gee ate agt ggg etc cag tet gag gat gag get gat tat 672

Ala Ser Leu Ala lie Ser Gly Leu Gin Ser Glu Asp Glu Ala Asp Tyr 210 215 220 tac tgt gca gca tgg gat gac ate ctg aat gtt ccg gta ttc ggc gga 720

Tyr Cys Ala Ala Trp Asp Asp lie Leu Asn Val Pro Val Phe Gly Gly 225 230 235 240 ggg acc aag ctg acc gtc eta ggt 744

Gly Thr Lys Leu Thr Val Leu Gly 245 <210> 116 <211 > 248 <212> PRT <213> Artificial <220> <223> Synthetic Construct <400> 116

Glu Val Gin Leu Val Glu Ser Gly Ala Glu Val Lys Lys Pro Gly Ser 15 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Pro Phe Arg Ser Tyr 20 25 30

Ala Ile Ser Trp Val Arg Gin Ala Pro Gly Gin Gly Pro Glu Trp Met 35 40 45

Gly Gly Ile Ile Pro Ile Phe Gly Thr Thr Lys Tyr Ala Pro Lys Phe 50 55 €0

Gin Gly Arg Val Thr Ile Thr Ala Asp Asp Phe Ala Gly Thr Val Tyr 65 70 75 80

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Met Tyr Tyr Cys 85 90 95

Ala Lys His Met Gly Tyr Gin Val Arg Glu Thr Met Asp Val Trp Gly 100 105 110

Lys Gly Thr Thr Val Thr Val Ser Ser Gly Thr Gly Gly Ser Gly Gly 115 120 125

Thr Gly Ser Gly Thr Gly Gly Ser Thr Ser Tyr Val Leu Thr Gin Pro 130 135 140

Pro Ser Ala Ser Gly Thr Pro Gly Gin Arg Val Thr Ile Ser Cys Ser 145 150 155 160

Gly Ser Thr Phe Asn Ile Gly Ser Asn Ala Val Asp Trp Tyr Arg Gin 165 170 175

Leu Pro Gly Thr Ala Pro Lys Leu Leu Ile Tyr Ser Asn Asn Gin Arg 180 185 190

Pro Ser Gly Val Pro Asp Arg Phe Ser Gly Ser Arg Ser Gly Thr Ser 195 200 205

Ala Ser Leu Ala Ile Ser Gly Leu Gin Ser Glu Asp Glu Ala Asp Tyr 210 215 220

Tyr Cys Ala Ala Trp Asp Asp Ile Leu Asn Val Pro Val Phe Gly Gly 225 230 235 240

Gly Thr Lys Leu Thr Val Leu Gly 245 <210> 117 <211> 744 <212> DNA <213> Artificial <220> <223> SC06-257 <220> <221 > CDS <222> (1) .. (744) <400> 117 cag gtc cag ctg gtg cag tct ggg get gag gtg aag aag cct ggg tec 48

Gin Val Gin Leu Val Gin Ser Gly Ala Glu Val Lys Lys Pro Gly Ser 15 10 15 teg gtg aaa gtc tct tgc aag get tct gga ggc ccc tte ege age tat 96

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Pro Phe Arg Ser Tyr 20 25 30 get ate age tgg gtg ega cag gee cet gga caa ggg cct gag tgg atg 144

Lys Gly Thr Thr Val Thr Val Ser Ser Gly Thr Gly Gly Ser Gly Gly 115 120 125 acc ggc age ggc act ggc ggg teg aeg cag tct gee ctg act cag cct 432

Thr Gly Ser Gly Thr Gly Gly Ser Thr Gin Ser Ala Leu Thr Gin Pro 130 135 140 gee gee gtg tct ggg tct cct gga cag teg ate acc ate tee tgc act 480

Ala Ala Val Ser Gly Ser Pro Gly Gin Ser lie Thr lie Ser Cys Thr 145 150 155 160 gga acc age agt gac gtt ggt ggt tat aac tat gtc tee tgg tac caa 528

Gly Thr Ser Ser Asp Val Gly Gly Tyr Asn Tyr Val Ser Trp Tyr Gin 165 170 175 cag cac cca ggc aaa gee ccc aaa etc atg att tat gag gtc agt aat 576

Gin His Pro Gly Lys Ala Pro Lys Leu Met lie Tyr Glu Val Ser Asn 180 185 190 egg ccc tea ggg gtt tct aat ege ttc tct ggc tee aag tct ggc aac 624

Arg Pro Ser Gly Val Ser Asn Arg Phe Ser Gly Ser Lys Ser Gly Asn 195 200 205 aeg gee tee ctg acc ate tct ggg etc cag get gag gac gag get gat 672

Thr Ala Ser Leu Thr lie Ser Gly Leu Gin Ala Glu Asp Glu Ala Asp 210 215 220 tat tac tgc age tea tat aca age age age act tat gtc ttc gga act 720

Tyr Tyr Cys Ser Ser Tyr Thr Ser Ser Ser Thr Tyr Val Phe Gly Thr 225 230 235 240 ggg acc aag gtc acc gtc eta ggt 744

Gly Thr Lys Val Thr Val Leu Gly 245 <210> 118 <211 > 248 <212> PRT <213> Artificial <220> <223> Synthetic Construct <400> 118

Gin Val Gin Leu Val Gin Ser Gly Ala Glu Val Lys Lys Pro Gly Ser 15 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Pro Phe Arg Ser Tyr 20 25 30

Ala Ile Ser Trp Val Arg Gin Ala Pro Gly Gin Gly Pro Glu Trp Met 35 40 45

Gly Gly lie lie Pro lie Phe Gly Thr Thr Lys Tyr Ala Pro Lys Phe 50 55 60

Gin Gly Arg Val Thr lie Thr Ala Asp Asp Phe Ala Gly Thr Val Tyr 65 70 75 80

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Met Tyr Tyr Cys 85 90 95

Ala Lys His Met Gly Tyr Gin Val Arg Glu Thr Met Asp Val Trp Gly 100 105 110

Lys Gly Thr Thr Val Thr Val Ser Ser Gly Thr Gly Gly Ser Gly Gly 115 120 125

Thr Gly Ser Gly Thr Gly Gly Ser Thr Gin Ser Ala Leu Thr Gin Pro 130 135 140

Ala Ala Val Ser Gly Ser Pro Gly Gin Ser He Thr lie Ser Cys Thr 145 150 155 160

Gly Thr Ser Ser Asp Val Gly Gly Tyr Asn Tyr Val Ser Trp Tyr Gin 165 170 175

Gin His Pro Gly Lys Ala Pro Lys Leu Met He Tyr Glu Val Ser Asn 180 185 190

Arg Pro Ser Gly Val Ser Asn Arg Phe Ser Gly Ser Lys Ser Gly Asn 195 200 205

Thr Ala Ser Leu Thr He Ser Gly Leu Gin Ala Glu Asp Glu Ala Asp 210 215 220

Tyr Tyr Cys Ser Ser Tyr Thr Ser Ser Ser Thr Tyr Val Phe Gly Thr 225 230 235 240

Gly Thr Lys Val Thr Val Leu Gly 245 <210> 119 <211> 744 <212> DNA <213> Artificial <220> <223> SC06-260 <220> <221 > CDS <222> (1) .. (744) <400> 119 gag gtg cag ctg gtg gag tct ggg get gag gtg aag aag cct ggg tee 48

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Pro Phe Arg Ser Tyr 20 25 30 get ate age tgg gtg ega eag gee cct gga eaa ggg cct gag tgg atg 144

Gly Gly He lie Pro He Phe Gly Thr Thr Lys Tyr Ala Pro Lys Phe 50 55 60 cag ggc aga gtc aeg att ace geg gac gat ttc geg ggc aca gtt tac 240

Ala Lys His Met Gly Tyr Gin Val Arg Glu Thr Met Asp Val Trp Gly

100 105 HO aaa ggg acc aeg gtc acc gtc teg age ggt aeg ggc ggt tea ggc gga 384

Thr Gly Ser Gly Thr Gly Gly Ser Thr Ser Tyr Val Leu Thr Gin Pro 130 135 140 ccc tea gtc tct ggg acc ccc ggg cag agg gtc acc ate tct tgc tct 480

Pro Ser Val Ser Gly Thr Pro Gly Gin Arg Val Thr He Ser Cys Ser 145 150 155 160 gga age ege tee aac gtc gga gat aat tct gta tat tgg tat eaa cac 528

Gly Ser Arg Ser Asn Val Gly Asp Asn Ser Val Tyr Trp Tyr Gin His 165 170 175 gtc cca gaa atg gee ccc aaa etc etc gtc tat aag aat act eaa egg 576

Val Pro Glu Met Ala Pro Lys Leu Leu Val Tyr Lys Asn Thr Gin Arg 180 185 190 ccc tea gga gtc cct gee egg ttt tee ggc tee aag tct ggc act tea 624

Pro Ser Gly Val Pro Ala Arg Phe Ser Gly Ser Lys Ser Gly Thr Ser 195 200 205 gee tee ctg gee ate att ggc etc cag tee ggc gat gag get gat tat 672

Ala Ser Leu Ala He He Gly Leu Gin Ser Gly Asp Glu Ala Asp Tyr 210 215 220 tat tgt gtg gca tgg gat gac age gta gat ggc tat gtc ttc gga tct 720

Tyr Cys Val Ala Trp Asp Asp Ser Val Asp Gly Tyr Val Phe Gly Ser 225 230 235 240 ggg acc aag gtc acc gtc eta ggt 744

Gly Thr Lys Val Thr Val Leu Gly 245 <210> 120 <211> 248 <212> PRT <213> Artificial <220> <223> Synthetic Construct <400> 120

Glu Val Gin Leu Val Glu Ser Gly Ala Glu Val Lys Lys Pro Gly Ser 15 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Pro Phe Arg Ser Tyr 20 25 30

Ala He Ser Trp Val Arg Gin Ala Pro Gly Gin Gly Pro Glu Trp Met 35 40 45

Gly Gly He He Pro lie Phe Gly Thr Thr Lys Tyr Ala Pro Lys Phe 50 55 60

Gin Gly Arg Val Thr Ile Thr Ala Asp Asp Phe Ala Gly Thr Val Tyr 65 70 75 80

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Met Tyr Tyr Cys 85 90 95

Ala Lys His Met Gly Tyr Gin Val Arg Glu Thr Met Asp Val Trp Gly 100 105 110

Lys Gly Thr Thr Val Thr Val Ser Ser Gly Thr Gly Gly Ser Gly Gly 115 120 125

Thr Gly Ser Gly Thr Gly Gly Ser Thr Ser Tyr Val Leu Thr Gin Pro 130 135 140

Pro Ser Val Ser Gly Thr Pro Gly Gin Arg Val Thr lie Ser Cys Ser 145 150 155 160

Gly Ser Arg Ser Asn Val Gly Asp Asn Ser Val Tyr Trp Tyr Gin His 165 170 175

Val Pro Glu Met Ala Pro Lys Leu Leu Val Tyr Lys Asn Thr Gin Arg 180 185 190

Pro Ser Gly Val Pro Ala Arg Phe Ser Gly Ser Lys Ser Gly Thr Ser 195 200 205

Ala Ser Leu Ala lie lie Gly Leu Gin Ser Gly Asp Glu Ala Asp Tyr 210 215 220

Tyr Cys Val Ala Trp Asp Asp Ser Val Asp Gly Tyr Val Phe Gly Ser 225 230 235 240

Gly Thr Lys Val Thr Val Leu Gly 245 <210> 121 <211> 747 <212> DNA <213> Artificial <220> <223> SC06-261 <220> <221 > CDS <222> (1)..(747) <400> 121 gag gtg cag ctg gtg gag tct ggg get gag gtg aag aag cct ggg tee 48

Lys Gly Thr Thr Val Thr Val Ser Ser Gly Thr Gly Gly Ser Gly Gly 115 120 125 acc ggc age ggc act ggc ggg teg aeg cag tct gtg ttg aeg cag ccg 432

Thr Gly Ser Gly Thr Gly Gly Ser Thr Gin Ser Val Leu Thr Gin Pro 130 135 140 ccc tea gtg tct geg gee cca gga cag aag gtc acc ate tee tgc tct 480

Pro Ser Val Ser Ala Ala Pro Gly Gin Lys Val Thr lie Ser Cys Ser 145 150 155 160 gga age age tee aac att ggg aat gat tat gta tee tgg tac cag cag 528

Gly Ser Ser Ser Asn lie Gly Asn Asp Tyr Val Ser Trp Tyr Gin Gin 165 170 175 etc cca gga aca gee ccc aaa etc etc att tat gac aat aat aag ega 576

Leu Pro Gly Thr Ala Pro Lys Leu Leu lie Tyr Asp Asn Asn Lys Arg 180 185 190 ccc tea ggg att cct gac ega ttc tct ggc tee aag tct ggc aeg tea 624

Pro Ser Gly lie Pro Asp Arg Phe Ser Gly Ser Lys Ser Gly Thr Ser 195 200 205 gee acc ctg ggc ate acc gga etc cag act ggg gac gag gee aac tat 672

Ala Thr Leu Gly lie Thr Gly Leu Gin Thr Gly Asp Glu Ala Asn Tyr 210 215 220 tac tgc gca aca tgg gat ege ege ccg act get tat gtt gtc ttc ggc 720

Tyr Cys Ala Thr Trp Asp Arg Arg Pro Thr Ala Tyr Val Val Phe Gly 225 230 235 240 gga ggg acc aag ctg acc gtc eta ggt 747

Gly Gly Thr Lys Leu Thr Val Leu Gly 245 <210> 122 <211 > 249 <212> PRT <213> Artificial <220> <223> Synthetic Construct <400> 122

Glu Val Gin Leu Val Glu Ser Gly Ala Glu Val Lys Lys Pro Gly Ser 15 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Pro Phe Arg Ser Tyr 20 25 30

Ala Ile Ser Trp Val Arg Gin Ala Pro Gly Gin Gly Pro Glu Trp Met 35 40 45

Gly Gly Ile Ile Pro Ile Phe Gly Thr Thr Lys Tyr Ala Pro Lys Phe 50 55 60

Gin Gly Arg Val Thr Ile Thr Ala Asp Asp Phe Ala Gly Thr Val Tyr 65 70 75 80

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Met Tyr Tyr Cys 85 90 95

Ala Lys His Met Gly Tyr Gin Val Arg Glu Thr Met Asp Val Trp Gly 100 105 110

Lys Gly Thr Thr Val Thr Val Ser Ser Gly Thr Gly Gly Ser Gly Gly 115 120 125

Thr Gly Ser Gly Thr Gly Gly Ser Thr Gin Ser Val Leu Thr Gin Pro 130 135 140

Pro Ser Val Ser Ala Ala Pro Gly Gin Lys Val Thr Ile Ser Cys Ser 145 150 155 160

Gly Ser Ser Ser Asn Ile Gly Asn Asp Tyr Val Ser Trp Tyr Gin Gin 165 170 175

Leu Pro Gly Thr Ala Pro Lys Leu Leu Ile Tyr Asp Asn Asn Lys Arg 180 185 190

Pro Ser Gly Ile Pro Asp Arg Phe Ser Gly Ser Lys Ser Gly Thr Ser 195 200 205

Ala Thr Leu Gly Ile Thr Gly Leu Gin Thr Gly Asp Glu Ala Asn Tyr 210 215 220

Tyr Cys Ala Thr Trp Asp Arg Arg Pro Thr Ala Tyr Val Val Phe Gly 225 230 235 240

Gly Gly Thr Lys Leu Thr Val Leu Gly 245 <210> 123 <211> 735 <212> DNA <213> Artificial <220> <223> SC06-262 <220> <221 > CDS <222> (1) .. (735) <400> 123 cag gta cag ctg cag cag tea ggg get gag gtg aag aag cct ggg tee 48

Ser Val Lys Val Ser Cys Lys Val Ser Gly Val lie Phe Ser Gly Ser 20 25 30 geg ate age tgg gtg ega eag gee cct gga caa ggc ett gag tgg atg 144

Gly Gly lie Ser Pro Leu Phe Gly Thr Thr Asn Tyr Ala Gin Lys Phe 50 55 60 cag ggc aga gtc aeg att acc geg gac caa tee aeg aac aca acc tac 240

Ala Arg Gly Pro Lys Tyr Tyr Ser Glu Tyr Met Asp Val Trp Gly Lys 100 105 110 ggg acc aeg gtc acc gtc teg age ggt aeg ggc ggt tea ggc gga acc 384

Gly Thr Thr Val Thr Val Ser Ser Gly Thr Gly Gly Ser Gly Gly Thr 115 120 125 ggc age ggc act ggc ggg teg aeg gac ate cag atg acc cag tet cca 432

Gly Ser Gly Thr Gly Gly Ser Thr Asp lie Gin Met Thr Gin Ser Pro 130 135 140 tee tee ctg tet gca tet gta gga gac aga gtc acc ate act tgc egg 480

Ser Ser Leu Ser Ala Ser Val Gly Asp Arg Val Thr lie Thr Cys Arg 145 150 155 160 geg agt cag ggc att age agt tat tta gee tgg tat cag cag aag cca 528

Ala Ser Gin Gly lie Ser Ser Tyr Leu Ala Trp Tyr Gin Gin Lys Pro 165 170 175 ggg aaa gtt cct aca etc ctg ate tat gat gca tee act ttg ega tea 576

Gly Lys Val Pro Thr Leu Leu lie Tyr Asp Ala Ser Thr Leu Arg Ser 180 185 190 ggg gtc cca tet ege ttc agt ggc agt gga tet geg aca gat ttc act 624

Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Ala Thr Asp Phe Thr 195 200 205 etc acc ate age age ctg cag cct gaa gat gtt gca act tat tac tgt 672

Leu Thr lie Ser Ser Leu Gin Pro Glu Asp Val Ala Thr Tyr Tyr Cys 210 215 220 caa agg tat aac agt gee ccc ccg ate acc ttc ggc caa ggg aca ega 720

Gin Arg Tyr Asn Ser Ala Pro Pro lie Thr Phe Gly Gin Gly Thr Arg 225 230 235 240 ctg gag att aaa cgt 735

Leu Glu lie Lys Arg 245 <210> 124 <211 > 245 <212> PRT <213> Artificial <220> <223> Synthetic Construct <400> 124

Gin Val Gin Leu Gin Gin Ser Gly Ala Glu Val Lys Lys Pro Gly Ser 15 10 15

Ser Val Lys Val Ser Cys Lys Val Ser Gly Val lie Phe Ser Gly Ser 20 25 30

Ala Ile Ser Trp Val Arg Gin Ala Pro Gly Gin Gly Leu Glu Trp Met 35 40 45

Gly Gly lie Ser Pro Leu Phe Gly Thr Thr Asn Tyr Ala Gin Lys Phe 50 55 60

Gin Gly Arg Val Thr lie Thr Ala Asp Gin Ser Thr Asn Thr Thr Tyr 65 70 75 80

Met Glu Val Asn Ser Leu Arg Tyr Glu Asp Thr Ala Val Tyr Phe Cys 85 90 95

Ala Arg Gly Pro Lys Tyr Tyr Ser Glu Tyr Met Asp Val Trp Gly Lys 100 105 110

Gly Thr Thr Val Thr Val Ser Ser Gly Thr Gly Gly Ser Gly Gly Thr 115 120 125

Gly Ser Gly Thr Gly Gly Ser Thr Asp lie Gin Met Thr Gin Ser Pro 130 135 140

Ser Ser Leu Ser Ala Ser Val Gly Asp Arg Val Thr lie Thr Cys Arg 145 150 155 160

Ala Ser Gin Gly lie Ser Ser Tyr Leu Ala Trp Tyr Gin Gin Lys Pro 165 170 175

Gly Lys Val Pro Thr Leu Leu lie Tyr Asp Ala Ser Thr Leu Arg Ser 180 185 190

Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Ala Thr Asp Phe Thr 195 200 205

Leu Thr lie Ser Ser Leu Gin Pro Glu Asp Val Ala Thr Tyr Tyr Cys 210 215 220

Gin Arg Tyr Asn Ser Ala Pro Pro lie Thr Phe Gly Gin Gly Thr Arg 225 230 235 240

Leu Glu lie Lys Arg 245 <210> 125 <211> 729 <212> DNA <213> Artificial <220> <223> SC06-268 <220> <221 > CDS <222> (1)..(729) <400> 125 cag gtc cag ctg gta cag tct ggg get gag gtg aag aag cct ggg tee 48

Gly Gly lie Met Gly Met Phe Gly Thr Thr Asn Tyr Ala Gin Lys Phe 50 55 60 cag ggc aga gtc aeg att ace geg gac gaa ttc aeg age gca gee tac 240

Ala Arg Ser Ser Gly Tyr Tyr Pro Glu Tyr Phe Gin Asp Trp Gly Gin 100 105 110 ggc ace ctg gtc acc gtc teg age ggt aeg ggc ggt tea ggc gga ace 384

Gly Thr Leu Val Thr Val Ser Ser Gly Thr Gly Gly Ser Gly Gly Thr 115 120 125 ggc age ggc act ggc ggg teg aeg cag tct gtg ctg act cag cca ccc 432

Gly Ser Gly Thr Gly Gly Ser Thr Gin Ser Val Leu Thr Gin Pro Pro 130 135 140 tea gag tee gtg tee cca gga cag aca gee age gtc acc tgc tct gga 480

Ser Glu Ser Val Ser Pro Gly Gin Thr Ala Ser Val Thr Cys Ser Gly 145 150 155 160 cat aaa ttg ggg gat aaa tat gtt teg tgg tat cag cag aag cca ggc 528

His Lys Leu Gly Asp Lys Tyr Val Ser Trp Tyr Gin Gin Lys Pro Gly 165 170 175 cag tee cct gta tta etc ate tat caa gat aac agg egg ccc tea ggg 576

Gin Ser Pro Val Leu Leu lie Tyr Gin Asp Asn Arg Arg Pro Ser Gly 180 185 190 ate cct gag ega ttc ata ggc tee aac tct ggg aac aca gee act ctg 624 lie Pro Glu Arg Phe lie Gly Ser Asn Ser Gly Asn Thr Ala Thr Leu 195 200 205 acc ate age ggg acc cag get ctg gat gag get gac tat tac tgt cag 672

Thr lie Ser Gly Thr Gin Ala Leu Asp Glu Ala Asp Tyr Tyr Cys Gin 210 215 220 geg tgg gac age age act geg gtt ttc ggc gga ggg acc aag ctg acc 720

Ala Trp Asp Ser Ser Thr Ala Val Phe Gly Gly Gly Thr Lys Leu Thr 225 230 235 240 gtc eta ggt 729

Val Leu Gly <210> 126 <211 > 243 <212> PRT <213> Artificial <220> <223> Synthetic Construct <400> 126

Gin Val Gin Leu Val Gin Ser Gly Ala Glu Val Lys Lys Pro Gly Ser 15 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Ser Ser Tyr 20 25 30

Ala lie Ser Trp Val Arg Gin Ala Pro Gly Gin Gly Leu Glu Trp Met 35 40 45

Gly Gly Ile Met Gly Met Phe Gly Thr Thr Asn Tyr Ala Gin Lys Phe 50 55 60

Gin Gly Arg Val Thr Ile Thr Ala Asp Glu Phe Thr Ser Ala Ala Tyr 65 70 75 80

Met Glu Leu Arg Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95

Ala Arg Ser Ser Gly Tyr Tyr Pro Glu Tyr Phe Gin Asp Trp Gly Gin 100 105 110

Gly Thr Leu Val Thr Val Ser Ser Gly Thr Gly Gly Ser Gly Gly Thr 115 120 125

Gly Ser Gly Thr Gly Gly Ser Thr Gin Ser Val Leu Thr Gin Pro Pro 130 135 140

Ser Glu Ser Val Ser Pro Gly Gin Thr Ala Ser Val Thr Cys Ser Gly 145 150 155 160

His Lys Leu Gly Asp Lys Tyr Val Ser Trp Tyr Gin Gin Lys Pro Gly 165 170 175

Gin Ser Pro Val Leu Leu Ile Tyr Gin Asp Asn Arg Arg Pro Ser Gly 180 185 190

Ile Pro Glu Arg Phe Ile Gly Ser Asn Ser Gly Asn Thr Ala Thr Leu 195 200 205

Thr Ile Ser Gly Thr Gin Ala Leu Asp Glu Ala Asp Tyr Tyr Cys Gin 210 215 220

Ala Trp Asp Ser Ser Thr Ala Val Phe Gly Gly Gly Thr Lys Leu Thr 225 230 235 240

Val Leu Gly <210> 127 <211> 738 <212> DNA <213> Artificial <220> <223> SC06-307 <220> <221 > CDS <222> (1)..(738) <400> 127 cag gtc cag ctg gtg cag tct ggg gga ggc ctg gtc aag cct ggg ggg 48

Gin Val Gin Leu Val Gin Ser Gly Gly Gly Leu Val Lys Pro Gly Gly 15 10 15 tcc ctg aga etc tee tgt gca gec tct gga tte acc tte agt age tat 96

Ser Met Asn Trp Val Arg Gin Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45 tea tec att agt agt agt agt agt tac ata tac tac gta gac tea gtg 192

Ser Ser lie Ser Ser Ser Ser Ser Tyr lie Tyr Tyr Val Asp Ser Val 50 55 60 aag ggc ega ttc acc ate tcc aga gac aac gcc aag aac tea ctg tat 240

Lys Gly Arg Phe Thr lie Ser Arg Asp Asn Ala Lys Asn Ser Leu Tyr 65 70 75 80 ctg caa atg aac age ctg aga gcc gag gac aeg get gtg tat tac tgt 288

Leu Gin Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 geg aga ggt ggt ggg age tac ggg gcc tac gaa ggc ttt gac tac tgg 336

Ala Arg Gly Gly Gly Ser Tyr Gly Ala Tyr Glu Gly Phe Asp Tyr Trp 100 105 110 ggc cag ggc acc ctg gtc acc gtc teg age ggt aeg ggc ggt tea ggc 384

Gly Gin Gly Thr Leu Val Thr Val Ser Ser Gly Thr Gly Gly Ser Gly 115 120 125 gga acc ggc age ggc act ggc ggg teg aeg gaa att gtg ctg act cag 432

Gly Thr Gly Ser Gly Thr Gly Gly Ser Thr Glu lie Val Leu Thr Gin 130 135 140 tct cca ggc acc ctg tct ttg tct cca ggg gaa aga gcc acc etc tcc 480

Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser 145 150 155 160 tgc agg gcc agt cag cgt gtt age age tac tta gcc tgg tac caa cag 528

Cys Arg Ala Ser Gin Arg Val Ser Ser Tyr Leu Ala Trp Tyr Gin Gin 165 170 175 aaa cct ggc cag get ccc agg etc etc ate tat ggt gca tcc acc agg 576

Lys Pro Gly Gin Ala Pro Arg Leu Leu lie Tyr Gly Ala Ser Thr Arg 180 185 190 gcc get ggc ate cca gac agg ttc agt ggc agt ggg tct ggg aca gac 624

Ala Ala Gly lie Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp 195 200 205 ttc act etc acc ate age aga ctg gag cct gaa gat tct gca gtg tat 672

Phe Thr Leu Thr lie Ser Arg Leu Glu Pro Glu Asp Ser Ala Val Tyr 210 215 220 tac tgt cag cag tat ggt agg aca ccg etc act ttc ggc gga ggg acc 720

Tyr Cys Gin Gin Tyr Gly Arg Thr Pro Leu Thr Phe Gly Gly Gly Thr 225 230 235 240 aag gtg gag ate aaa cgt 738

Lys Val Glu lie Lys Arg 245 <210> 128 <211 > 246 <212> PRT <213> Artificial <220> <223> Synthetic Construct <400> 128

Gin Val Gin Leu Val Gin Ser Gly Gly Gly Leu Val Lys Pro Gly Gly 15 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Ser Tyr 20 25 30

Ser Met Asn Trp Val Arg Gin Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45

Ser Ser lie Ser Ser Ser Ser Ser Tyr lie Tyr Tyr Val Asp Ser Val 50 55 60

Lys Gly Arg Phe Thr lie Ser Arg Asp Asn Ala Lys Asn Ser Leu Tyr 65 70 75 80

Leu Gin Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95

Ala Arg Gly Gly Gly Ser Tyr Gly Ala Tyr Glu Gly Phe Asp Tyr Trp 100 105 110

Gly Gin Gly Thr Leu Val Thr Val Ser Ser Gly Thr Gly Gly Ser Gly 115 120 125

Gly Thr Gly Ser Gly Thr Gly Gly Ser Thr Glu lie Val Leu Thr Gin 130 135 140

Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser 145 150 155 160

Cys Arg Ala Ser Gin Arg Val Ser Ser Tyr Leu Ala Trp Tyr Gin Gin 165 170 175

Lys Pro Gly Gin Ala Pro Arg Leu Leu lie Tyr Gly Ala Ser Thr Arg 180 185 190

Ala Ala Gly lie Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp 195 200 205

Phe Thr Leu Thr lie Ser Arg Leu Glu Pro Glu Asp Ser Ala Val Tyr 210 215 220

Tyr Cys Gin Gin Tyr Gly Arg Thr Pro Leu Thr Phe Gly Gly Gly Thr 225 230 235 240

Lys Val Glu lie Lys Arg 245 <210> 129 <211> 738 <212> DNA <213> Artificial <220> <223> SC06-310 <220> <221 > CDS <222> (1)..(738) <400> 129 gag gtg cag ctg gtg gag tct ggg get gag gtg aag aag cct ggg tee 48

Thr Gly Ser Gly Thr Gly Gly Ser Thr Ser Tyr Val Leu Thr Gin Pro 130 135 140 ccc teg gtg tea gtg gee cca gga cag aeg gee agg att acc tgt ggg 480

Pro Ser Val Ser Val Ala Pro Gly Gin Thr Ala Arg lie Thr Cys Gly 145 150 155 160 gga aac aac att gga agt aaa agt gtg cac tgg tac cag cag aag cca 528

Gly Asn Asn lie Gly Ser Lys Ser Val His Trp Tyr Gin Gin Lys Pro 165 170 175 ggc cag gee cct gtg ctg gtc gtc tat gat gat age gac egg ccc tea 576

Gly Gin Ala Pro Val Leu Val Val Tyr Asp Asp Ser Asp Arg Pro Ser 180 185 190 ggg ate cct gag ega ttc tct ggc tee aac tct ggg aac aeg gee acc 624

Gly lie Pro Glu Arg Phe Ser Gly Ser Asn Ser Gly Asn Thr Ala Thr 195 200 205 ctg acc ate age agg gtc gaa gee ggg gat gag gee gac tat tac tgt 672

Leu Thr lie Ser Arg Val Glu Ala Gly Asp Glu Ala Asp Tyr Tyr Cys 210 215 220 cag gtg tgg gat agt agt agt gat cat get gtg ttc gga gga ggc acc 720

Gin Val Trp Asp Ser Ser Ser Asp His Ala Val Phe Gly Gly Gly Thr 225 230 235 240 cag ctg acc gtc etc ggt 738

Gin Leu Thr Val Leu Gly 245 <210> 130 <211 > 246 <212> PRT <213> Artificial <220> <223> Synthetic Construct <400> 130

Glu Val Gin Leu Val Glu Ser Gly Ala Glu Val Lys Lys Pro Gly Ser 15 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Pro Phe Arg Ser Tyr 20 25 30

Ala Ile Ser Trp Val Arg Gin Ala Pro Gly Gin Gly Pro Glu Trp Met 35 40 45

Gly Gly Ile Ile Pro Ile Phe Gly Thr Thr Lys Tyr Ala Pro Lys Phe 50 55 60

Gin Gly Arg Val Thr Ile Thr Ala Asp Asp Phe Ala Gly Thr Val Tyr 65 70 75 80

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Met Tyr Tyr Cys 85 90 95

Ala Lys His Met Gly Tyr Gin Val Arg Glu Thr Met Asp Val Trp Gly 100 105 110

Lys Gly Thr Thr Val Thr Val Ser Ser Gly Thr Gly Gly Ser Gly Gly 115 120 125

Thr Gly Ser Gly Thr Gly Gly Ser Thr Ser Tyr Val Leu Thr Gin Pro 130 135 140

Pro Ser Val Ser Val Ala Pro Gly Gin Thr Ala Arg Ile Thr Cys Gly 145 150 155 160

Gly Asn Asn Ile Gly Ser Lys Ser Val His Trp Tyr Gin Gin Lys Pro 165 170 175

Gly Gin Ala Pro Val Leu Val Val Tyr Asp Asp Ser Asp Arg Pro Ser 180 185 190

Gly Ile Pro Glu Arg Phe Ser Gly Ser Asn Ser Gly Asn Thr Ala Thr 195 200 205

Leu Thr Ile Ser Arg Val Glu Ala Gly Asp Glu Ala Asp Tyr Tyr Cys 210 215 220

Gin Val Trp Asp Ser Ser Ser Asp His Ala Val Phe Gly Gly Gly Thr 225 230 235 240

Gin Leu Thr Val Leu Gly 245 <210> 131 <211> 744 <212> DNA <213> Artificial <220> <223> SC06-314 <220> <221 > CDS <222> (1) .. (744) <400> 131 gag gtg cag ctg gtg gag tct ggg get gag gtg aag aag cct ggg tee 48

Thr Gly Ser Gly Thr Gly Gly Ser Thr Ser Tyr Val Leu Thr Gin Pro 130 135 140 ccc tea geg tct ggg acc ccc ggg cag agg gtc acc ate tct tgt tct 480

Pro Ser Ala Ser Gly Thr Pro Gly Gin Arg Val Thr lie Ser Cys Ser 145 150 155 160 gga age age tee aac ate gga agt aat tat gta tac tgg tac cag cag 528

Gly Ser Ser Ser Asn lie Gly Ser Asn Tyr Val Tyr Trp Tyr Gin Gin 165 170 175 etc cca ggc aeg gee ccc aaa etc etc ate tat agg gat ggt cag egg 576

Leu Pro Gly Thr Ala Pro Lys Leu Leu lie Tyr Arg Asp Gly Gin Arg 180 185 190 ccc tea ggg gtc cct gac ega ttc tct ggc tee aag tct ggc acc tea 624

Pro Ser Gly Val Pro Asp Arg Phe Ser Gly Ser Lys Ser Gly Thr Ser 195 200 205 gee tee ctg gee ate agt gga etc egg tee gat gat gag get gat tat 672

Ala Ser Leu Ala lie Ser Gly Leu Arg Ser Asp Asp Glu Ala Asp Tyr 210 215 220 tac tgt gca aca tgg gat gac aac ctg agt ggt cca gta ttc ggc gga 720

Tyr Cys Ala Thr Trp Asp Asp Asn Leu Ser Gly Pro Val Phe Gly Gly 225 230 235 240 ggg acc aag ctg acc gtc eta ggt 744

Gly Thr Lys Leu Thr Val Leu Gly 245 <210> 132 <211> 248 <212> PRT <213> Artificial <220> <223> Synthetic Construct <400> 132

Glu Val Gin Leu Val Glu Ser Gly Ala Glu Val Lys Lys Pro Gly Ser 15 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Pro Phe Arg Ser Tyr 20 25 30

Ala Ile Ser Trp Val Arg Gin Ala Pro Gly Gin Gly Pro Glu Trp Met 35 40 45

Gly Gly Ile Ile Pro Ile Phe Gly Thr Thr Lys Tyr Ala Pro Lys Phe 50 55 60

Gin Gly Arg Val Thr Ile Thr Ala Asp Asp Phe Ala Gly Thr Val Tyr 65 70 75 80

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Met Tyr Tyr Cys 85 90 95

Ala Lys His Met Gly Tyr Gin Val Arg Glu Thr Met Asp Val Trp Gly 100 105 110

Lys Gly Thr Thr Val Thr Val Ser Ser Gly Thr Gly Gly Ser Gly Gly 115 120 125

Thr Gly Ser Gly Thr Gly Gly Ser Thr Ser Tyr Val Leu Thr Gin Pro 130 135 140

Pro Ser Ala Ser Gly Thr Pro Gly Gin Arg Val Thr Ile Ser Cys Ser 145 150 155 160

Gly Ser Ser Ser Asn Ile Gly Ser Asn Tyr Val Tyr Trp Tyr Gin Gin 165 170 175

Leu Pro Gly Thr Ala Pro Lys Leu Leu Ile Tyr Arg Asp Gly Gin Arg 180 185 190

Pro Ser Gly Val Pro Asp Arg Phe Ser Gly Ser Lys Ser Gly Thr Ser 195 200 205

Ala Ser Leu Ala Ile Ser Gly Leu Arg Ser Asp Asp Glu Ala Asp Tyr 210 215 220

Tyr Cys Ala Thr Trp Asp Asp Asn Leu Ser Gly Pro Val Phe Gly Gly 225 230 235 240

Gly Thr Lys Leu Thr Val Leu Gly 245 <210> 133 <211> 735 <212> DNA <213> Artificial <220> <223> SC06-323 <220> <221 > CDS <222> (1) .. (735) <400> 133 gag gtg cag ctg gtg gag tct ggg get gag gtg aag aag cca ggg tee 48

Glu Val Gin Leu Val Glu Ser Gly Ala Glu Val Lys Lys Pro Gly Ser 15 10 15 teg gtg aag gtc tee tgt aag gee tct gga ggc ace ttc tee age tat 96

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Ser Ser Tyr 20 25 30 ggt ate age tgg gtg ega cag gee cct gga caa ggg ett gag tgg atg 144

Gly Ile Ser Trp Val Arg Gin Ala Pro Gly Gin Gly Leu Glu Trp Met 35 40 45 gga gac ate ate ggt atg ttt ggt tea aca aae tac gca cag aac ttc 192

Gly Asp lie lie Gly Met Phe Gly Ser Thr Asn Tyr Ala Gin Asn Phe 50 55 60 cag ggc aga etc aeg att ace geg gac gaa tee aeg age aca gee tac 240

Gin Gly Arg Leu Thr lie Thr Ala Asp Glu Ser Thr Ser Thr Ala Tyr 65 70 75 80 atg gag ctg age age ctg aga tct gag gac aeg gee gtg tat tac tgt 288

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 geg aga agt agt ggt tat tac cct gca tac etc ccc cac tgg ggc cag 336

Ala Arg Ser Ser Gly Tyr Tyr Pro Ala Tyr Leu Pro His Trp Gly Gin 100 105 110 ggc acc ttg gtc ace gtc teg age ggt aeg ggc ggt tea ggc gga acc 384

Gly Thr Leu Val Thr Val Ser Ser Gly Thr Gly Gly Ser Gly Gly Thr 115 120 125 ggc age ggc act ggc ggg teg aeg gaa att gtg ttg acc cag tct cca 432

Gly Ser Gly Thr Gly Gly Ser Thr Glu lie Val Leu Thr Gin Ser Pro 130 135 140 ggc acc ctg tct ttg tct cca ggg gaa aga gee acc etc tee tgc agg 480

Gly Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys Arg 145 150 155 160 gee agt cag agt gtt age age age tac tta gee tgg tac cag cag aaa 528

Ala Ser Gin Ser Val Ser Ser Ser Tyr Leu Ala Trp Tyr Gin Gin Lys 165 170 175 cct ggc cag get ccc agg etc etc ate tat ggt gca tee age agg gee 576

Pro Gly Gin Ala Pro Arg Leu Leu lie Tyr Gly Ala Ser Ser Arg Ala 180 185 190 act ggc ate cca gac agg ttc agt ggc agt ggg tct ggg aca gac ttc 624

Thr Gly lie Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe 195 200 205 act etc acc ate age aga ctg gag cct gaa gat ttt gca gtg tat tac 672

Thr Leu Thr lie Ser Arg Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr 210 215 220 tgt cag cag tat ggt age tea ccc aga act ttc ggc gga ggg acc aag 720

Cys Gin Gin Tyr Gly Ser Ser Pro Arg Thr Phe Gly Gly Gly Thr Lys 225 230 235 240 gtg gag ate aaa cgt 735

Val Glu lie Lys Arg 245 <210> 134 <211 > 245 <212> PRT <213> Artificial <220> <223> Synthetic Construct <400> 134

Glu Val Gin Leu Val Glu Ser Gly Ala Glu Val Lys Lys Pro Gly Ser 15 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Ser Ser Tyr 20 25 30

Gly Ile Ser Trp Val Arg Gin Ala Pro Gly Gin Gly Leu Glu Trp Met 35 40 45

Gly Asp Ile Ile Gly Met Phe Gly Ser Thr Asn Tyr Ala Gin Asn Phe 50 55 €0

Gin Gly Arg Leu Thr Ile Thr Ala Asp Glu Ser Thr Ser Thr Ala Tyr 65 70 75 80

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95

Ala Arg Ser Ser Gly Tyr Tyr Pro Ala Tyr Leu Pro His Trp Gly Gin 100 105 110

Gly Thr Leu Val Thr Val Ser Ser Gly Thr Gly Gly Ser Gly Gly Thr 115 120 125

Gly Ser Gly Thr Gly Gly Ser Thr Glu Ile Val Leu Thr Gin Ser Pro 130 135 140

Gly Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys Arg 145 150 155 160

Ala Ser Gin Ser Val Ser Ser Ser Tyr Leu Ala Trp Tyr Gin Gin Lys 165 170 175

Pro Gly Gin Ala Pro Arg Leu Leu Ile Tyr Gly Ala Ser Ser Arg Ala 180 185 190

Thr Gly Ile Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe 195 200 205

Thr Leu Thr Ile Ser Arg Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr 210 215 220

Cys Gin Gin Tyr Gly Ser Ser Pro Arg Thr Phe Gly Gly Gly Thr Lys 225 230 235 240

Val Glu Ile Lys Arg 245 <210> 135 <211> 744 <212> DNA <213> Artificial <220> <223> SC06-325 <220> <221 > CDS <222> (1) .. (744) <400> 135 gag gtg cag ctg gtg gag tct ggg get gag gtg aag aag ccg ggg tee 48

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Ser Phe Tyr 20 25 30 tct atg age tgg gtg ega cag gee cet gga eaa gga ett gag tgg atg 144

Ser Met Ser Trp Val Arg Gin Ala Pro Gly Gin Gly Leu Glu Trp Met 35 40 45 gga ggg ate ate cet atg ttt ggt aca aca aac tac gca cag aag ttc 192

Gly Gly lie lie Pro Met Phe Gly Thr Thr Asn Tyr Ala Gin Lys Phe 50 55 60 cag ggc aga gtc aeg att acc geg gtc gaa tee aeg age aca gee tac 240

Ala Arg Gly Asp Lys Gly lie Tyr Tyr Tyr Tyr Met Asp Val Trp Gly 100 105 110 aaa ggg acc aeg gtc acc gtc teg age ggt aeg ggc ggt tea ggc gga 384

Lys Gly Thr Thr Val Thr Val Ser Ser Gly Thr Gly Gly Ser Gly Gly 115 120 125 acc ggc age ggc act ggc ggg teg aeg cag tct gee ctg act cag cet 432

Thr Gly Ser Gly Thr Gly Gly Ser Thr Gin Ser Ala Leu Thr Gin Pro 130 135 140 gee tee gtg tct ggg tct cet gga cag teg ate acc ate tee tgc act 480

Ala Ser Val Ser Gly Ser Pro Gly Gin Ser lie Thr lie Ser Cys Thr 145 150 155 160 gga acc age agt gac gtt ggt ggt tat aac tat gtc tee tgg tac eaa 528

Thr Ala Ser Leu Thr lie Ser Gly Leu Gin Ala Glu Asp Glu Ala Asp 210 215 220 tat tac tgc age tea tat aca age age age aet ett gtc ttc gga act 720

Tyr Tyr Cys Ser Ser Tyr Thr Ser Ser Ser Thr Leu Val Phe Gly Thr 225 230 235 240 ggg acc aag gtc acc gtc eta ggt 744

Gly Thr Lys Val Thr Val Leu Gly 245 <210> 136 <211 > 248 <212> PRT <213> Artificial <220> <223> Synthetic Construct <400> 136

Glu Val Gin Leu Val Glu Ser Gly Ala Glu Val Lys Lys Pro Gly Ser 15 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Ser Phe Tyr 20 25 30

Ser Met Ser Trp Val Arg Gin Ala Pro Gly Gin Gly Leu Glu Trp Met 35 40 45

Gly Gly Ile Ile Pro Met Phe Gly Thr Thr Asn Tyr Ala Gin Lys Phe 50 55 60

Gin Gly Arg Val Thr Ile Thr Ala Val Glu Ser Thr Ser Thr Ala Tyr 65 70 75 80

Met Glu Val Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95

Ala Arg Gly Asp Lys Gly Ile Tyr Tyr Tyr Tyr Met Asp Val Trp Gly 100 105 110

Lys Gly Thr Thr Val Thr Val Ser Ser Gly Thr Gly Gly Ser Gly Gly 115 120 125

Thr Gly Ser Gly Thr Gly Gly Ser Thr Gin Ser Ala Leu Thr Gin Pro 130 135 140

Ala Ser Val Ser Gly Ser Pro Gly Gin Ser Ile Thr Ile Ser Cys Thr 145 150 155 160

Gly Thr Ser Ser Asp Val Gly Gly Tyr Asn Tyr Val Ser Trp Tyr Gin 165 170 175

Gin His Pro Gly Lys Ala Pro Lys Leu Met Ile Tyr Glu Val Ser Asn 180 185 190

Arg Pro Ser Gly Val Ser Asn Arg Phe Ser Gly Ser Lys Ser Gly Asn 195 200 205

Thr Ala Ser Leu Thr Ile Ser Gly Leu Gin Ala Glu Asp Glu Ala Asp 210 215 220

Tyr Tyr Cys Ser Ser Tyr Thr Ser Ser Ser Thr Leu Val Phe Gly Thr 225 230 235 240

Gly Thr Lys Val Thr Val Leu Gly 245 <210> 137 <211> 735 <212> DNA <213> Artificial <220> <223> SC06-331 <220> <221 > CDS <222> (1) .. (735) <400> 137 gag gtg cag ctg gtg gag tct ggg get gag gtg aag aag cct ggg tee 48

Glu Val Gin Leu Val Glu Ser Gly Ala Glu Val Lys Lys Pro Gly Ser 15 10 15 teg gtg aag gtc tee tgc aag get tct gga ggc acc ttc age age tat 96

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Ser Ser Tyr 20 25 30 get atc age tgg gtg ega cag gcc cct gga caa ggg ett gag tgg atg 144

Ala Ile Ser Trp Val Arg Gin Ala Pro Gly Gin Gly Leu Glu Trp Met 35 40 45 gga ggg atc atc ggt atg ttc ggt aca gca aac tac gca cag aag ttc 192

Gly Gly Ile Ile Gly Met Phe Gly Thr Ala Asn Tyr Ala Gin Lys Phe 50 55 60 cag ggc aga gtc acg att acc gcg gac gaa ttt acg age aca gce tac 240

Gin Gly Arg Val Thr Ile Thr Ala Asp Glu Phe Thr Ser Thr Ala Tyr 65 70 75 80 atg gag ctg age age ctg aga tet gag gac acg gcc gtg tat tac tgt 288

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 gcg aga gga aat tat tac tat gag agt agt ctc gac tac tgg ggc cag 336

Ala Arg Gly Asn Tyr Tyr Tyr Glu Ser Ser Leu Asp Tyr Trp Gly Gin 100 105 110 gga acc ctg gtc acc gtc teg age ggt acg ggc ggt tea ggc gga acc 384

Gly Thr Leu Val Thr Val Ser Ser Gly Thr Gly Gly Ser Gly Gly Thr 115 120 125 ggc age ggc act ggc ggg teg acg cag tet gtc gtg acg cag ccg ccc 432

Gly Ser Gly Thr Gly Gly Ser Thr Gin Ser Val Val Thr Gin Pro Pro 130 135 140 teg gtg tea gtg gcc cca gga cag acg gcc agg att acc tgt ggg gga 480

Ser Val Ser Val Ala Pro Gly Gin Thr Ala Arg Ile Thr Cys Gly Gly 145 150 155 160 aac aac att gga agt aaa agt gtg cac tgg tac cag cag aag cca ggc 528

Asn Asn Ile Gly Ser Lys Ser Val His Trp Tyr Gin Gin Lys Pro Gly 165 170 175 cag gcc cct gtg ctg gtc gtc tat gat gat age gac egg ccc tea ggg 576

Gin Ala Pro Val Leu Val Val Tyr Asp Asp Ser Asp Arg Pro Ser Gly 180 185 190 atc cct gag ega ttc tet ggc tee aac tet ggg aac acg gcc acc ctg 624

Ile Pro Glu Arg Phe Ser Gly Ser Asn Ser Gly Asn Thr Ala Thr Leu 195 200 205 acc atc age agg gtc gaa gcc ggg gat gag gcc gac tat tac tgt cag 672

Thr Ile Ser Arg Val Glu Ala Gly Asp Glu Ala Asp Tyr Tyr Cys Gin 210 215 220 gtg tgg gat agt agt agt gat cat tat gtc ttc gga act ggg acc aag 720

Val Trp Asp Ser Ser Ser Asp His Tyr Val Phe Gly Thr Gly Thr Lys 225 230 235 240 gtc acc gtc eta ggt 735

Val Thr Val Leu Gly 245 <210> 138 <211 > 245 <212> PRT <213> Artificial <220> <223> Synthetic Construct <400> 138

Glu Val Gin Leu Val Glu Ser Gly Ala Glu Val Lys Lys Pro Gly Ser 15 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Ser Ser Tyr 20 25 30

Ala Ile Ser Trp Val Arg Gin Ala Pro Gly Gin Gly Leu Glu Trp Met 35 40 45

Gly Gly Ile Ile Gly Met Phe Gly Thr Ala Asn Tyr Ala Gin Lys Phe 50 55 60

Gin Gly Arg Val Thr Ile Thr Ala Asp Glu Phe Thr Ser Thr Ala Tyr 65 70 75 80

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95

Ala Arg Gly Asn Tyr Tyr Tyr Glu Ser Ser Leu Asp Tyr Trp Gly Gin 100 105 110

Gly Thr Leu Val Thr Val Ser Ser Gly Thr Gly Gly Ser Gly Gly Thr 115 120 125

Gly Ser Gly Thr Gly Gly Ser Thr Gin Ser Val Val Thr Gin Pro Pro 130 135 140

Ser Val Ser Val Ala Pro Gly Gin Thr Ala Arg Ile Thr Cys Gly Gly 145 150 155 160

Asn Asn Ile Gly Ser Lys Ser Val His Trp Tyr Gin Gin Lys Pro Gly 165 170 175

Gin Ala Pro Val Leu Val Val Tyr Asp Asp Ser Asp Arg Pro Ser Gly 180 185 190

Ile Pro Glu Arg Phe Ser Gly Ser Asn Ser Gly Asn Thr Ala Thr Leu 195 200 205

Thr Ile Ser Arg Val Glu Ala Gly Asp Glu Ala Asp Tyr Tyr Cys Gin 210 215 220

Val Trp Asp Ser Ser Ser Asp His Tyr Val Phe Gly Thr Gly Thr Lys 225 230 235 240

Val Thr Val Leu Gly 245 <210> 139 <211> 750 <212> DNA <213> Artificial <220> <223> SC06-344 <220> <221 > CDS <222> (1)..(750) <400> 139 cag gtg cag ctg gtg cag tct ggg get gag gtg aag aag cct ggg tee 48

Gly Gly lie lie Ala lie Phe Gly Thr Pro Lys Tyr Ala Gin Lys Phe 50 55 60 cag ggc aga gtc aeg att ace geg gac gaa teg aeg age act gtc tac 240

Ala Arg lie Pro His Tyr Asn Phe Gly Ser Gly Ser Tyr Phe Asp Tyr 100 105 110 tgg ggc cag gga acc ctg gtc acc gtc teg age ggt aeg ggc ggt tea 384

Trp Gly Gin Gly Thr Leu Val Thr Val Ser Ser Gly Thr Gly Gly Ser 115 120 125 ggc gga acc ggc age ggc act ggc ggg teg aeg act gtg ttg aca cag 432

Gly Gly Thr Gly Ser Gly Thr Gly Gly Ser Thr Thr Val Leu Thr Gin 130 135 140 ccg ccc tea gtg tct ggg gee cca ggg cag agg gtc acc ate tee tgc 480

Pro Pro Ser Val Ser Gly Ala Pro Gly Gin Arg Val Thr lie Ser Cys 145 150 155 160 act ggg age age tee aac ate ggg gca ggt tat gat gta cac tgg tac 528

Thr Gly Ser Ser Ser Asn lie Gly Ala Gly Tyr Asp Val His Trp Tyr 165 170 175 cag cag ett cca gga aca gee ccc aaa etc etc ate tat ggt aac age 576

Gin Gin Leu Pro Gly Thr Ala Pro Lys Leu Leu lie Tyr Gly Asn Ser 180 185 190 aat egg ccc tea ggg gtc cct gac ega ttc tct ggc tee aag tct ggc 624

Asn Arg Pro Ser Gly Val Pro Asp Arg Phe Ser Gly Ser Lys Ser Gly 195 200 205 aeg tea gee acc ctg ggc ate acc gga etc cag act ggg gac gag gee 672

Thr Ser Ala Thr Leu Gly lie Thr Gly Leu Gin Thr Gly Asp Glu Ala 210 215 220 gat tat tac tgc gga aca tgg gat age age ctg agt get tat gtc ttc 720

Asp Tyr Tyr Cys Gly Thr Trp Asp Ser Ser Leu Ser Ala Tyr Val Phe 225 230 235 240 gga act ggg acc aag gtc acc gtc eta ggt 750

Gly Thr Gly Thr Lys Val Thr Val Leu Gly 245 250 <210> 140 <211 > 250 <212> PRT <213> Artificial <220> <223> Synthetic Construct <400>140

Gin Val Gin Leu Val Gin Ser Gly Ala Glu Val Lys Lys Pro Gly Ser 15 10 15

Ser Val Arg Val Ser Cys Lys Ala Ser Gly Ser Ile Phe Arg Asn Tyr 20 25 30

Ala Met Ser Trp Val Arg Gin Ala Pro Gly Gin Gly Leu Glu Trp Met 35 40 45

Gly Gly lie lie Ala lie Phe Gly Thr Pro Lys Tyr Ala Gin Lys Phe 50 55 60

Gin Gly Arg Val Thr Ile Thr Ala Asp Glu Ser Thr Ser Thr Val Tyr 65 70 75 80

Met Glu Leu Ser Gly Leu Arg Ser Glu Asp Thr Ala Met Tyr Tyr Cys 85 90 95

Ala Arg lie Pro His Tyr Asn Phe Gly Ser Gly Ser Tyr Phe Asp Tyr 100 105 110

Trp Gly Gin Gly Thr Leu Val Thr Val Ser Ser Gly Thr Gly Gly Ser 115 120 125

Gly Gly Thr Gly Ser Gly Thr Gly Gly Ser Thr Thr Val Leu Thr Gin 130 135 140

Pro Pro Ser Val Ser Gly Ala Pro Gly Gin Arg Val Thr He Ser Cys 145 150 155 160

Thr Gly Ser Ser Ser Asn lie Gly Ala Gly Tyr Asp Val His Trp Tyr 165 170 175

Gin Gin Leu Pro Gly Thr Ala Pro Lys Leu Leu He Tyr Gly Asn Ser 180 185 190

Asn Arg Pro Ser Gly Val Pro Asp Arg Phe Ser Gly Ser Lys Ser Gly 195 200 205

Thr Ser Ala Thr Leu Gly He Thr Gly Leu Gin Thr Gly Asp Glu Ala 210 215 220

Asp Tyr Tyr Cys Gly Thr Trp Asp Ser Ser Leu Ser Ala Tyr Val Phe 225 230 235 240

Gly Thr Gly Thr Lys Val Thr Val Leu Gly 245 250 <210> 141 <211 > 10515 <212> DNA <213> Artificial <220> <223> Vector plg-C911-HCgammal <220> <221 > misc_feature <222> (1326)..(5076) <223> Stuffer <400> 141 tcgacggatc gggagatctc ccgatcccct atggtgcact ctcagtacaa tctgctctga 60 tgccgcatag ttaagccagt atctgctccc tgcttgtgtg ttggaggtcg ctgagtagtg 120 cgcgagcaaa atttaagcta caacaaggca aggcttgacc gacaattgca tgaagaatct 180 gcttagggtt aggcgttttg cgctgcttcg ctaggtggtc aatattggcc attagccata 240 ttattcattg gttatatagc ataaatcaat attggctatt ggccattgca tacgttgtat 300 ccatatcata atatgtacat ttatattggc tcatgtccaa cattaccgcc atgttgacat 360 tgattattga ctagttatta atagtaatca attacggggt cattagttca tagcccatat 420 atggagttcc gcgttacata acttacggta aatggcccgc ctggctgacc gcccaacgac 480 ccccgcccat tgacgtcaat aatgacgtat gttcccatag taacgccaat agggactttc 540 cattgacgtc aatgggtgga gtatttacgg taaactgccc acttggcagt acatcaagtg 600 tatcatatgc caagtacgcc ccctattgac gtcaatgacg gtaaatggcc cgcctggcat 660 tatgcccagt acatgacctt atgggacttt cctacttggc agtacatcta cgtattagtc 720 atcgctatta ccatggtgat gcggttttgg cagtacatca atgggcgtgg atagcggttt 780 gactcacggg gatttccaag tctccacccc attgacgtca atgggagttt gttttggcac 840 caaaatcaac gggactttcc aaaatgtcgt aacaactccg ccccattgac gcaaatgggc 900 ggtaggcgtg tacggtggga ggtctatata agcagagctc gtttagtgaa ccgtcagatc 960 gcctggagac gccatccacg ctgttttgac ctccatagaa gacaccggga ccgatccagc 1020 ctccgcggcc gggaacggtg cattggaagc tggcctggat atcctgactc tcttaggtag 1080 ccttgcagaa gttggrtcgtg aggcactggg caggtaagta tcaaggttac aagacaggtt 1140 taaggagatc aatagaaact gggcttgtcg agacagagaa gactcttgcg tttctgatag 1200 gcacctattg gtcttactga catccacttt gcctttctct ccacaggtgt ccactcccag 1260 ttcaattaca gctcgccacc atgggatgga gctgtatcat cctcttcttg gtactgctgc 1320 tggcccagcc ggccagtgac cttgaccggt gcaccacttt tgatgatgtt caagctccta 1380 attacactca acatacttca tctatgaggg gggtttacta tcctgatgaa atttttagat 1440 cggacaetet ttatttaact caggatttat ttcttccatt ttattctaat gttacagggt 1500 ttcatactat taatcatacg tttggcaacc ctgtcatacc ttttaaggat ggtatttatt 1560 ttgctgccac agagaaatca aatgttgtcc gtggttgggt ttttggttct accatgaaca 1620 acaagtcaca gtcggtgatt attattaaca attctactaa tgttgttata cgagcatgta 1680 actttgaatt gtgtgacaac cctttctttg ctgtttctaa acccatgggt acacagacac 1740 atactatgat attcgataat gcatttaatt gcactttcga gtacatatct gatgcctttt 1800 cgcttgatgt ttcagaaaag tcaggtaatt ttaaacactt acgagagttt gtgtttaaaa 1860 ataaagatgg gtttctctat gtttataagg gctatcaacc tatagatgta gttcgtgatc 1920 taccttctgg ttttaacact ttgaaaccta tttttaagtt gcctcttggt attaacatta 1980 caaattttag agccattctt acagcctttt cacctgctca agacatttgg ggcacgtcag 2040 ctgcagccta ttttgttggc tatttaaagc caactacatt tatgctcaag tatgatgaaa 2100 atggtacaat cacagatgct gttgattgtt ctcaaaatcc acttgctgaa ctcaaatgct 2160 ctgttaagag ctttgagatt gacaaaggaa tttaccagac ctctaatttc agggttgttc 2220 cctcaggaga tgttgtgaga ttccctaata ttacaaactt gtgtcctttt ggagaggttt 2280 ttaatgctac taaattccct tctgtctatg catgggagag aaaaaaaatt tctaattgtg 2340 ttgctgatta ctctgtgctc tacaactcaa catttttttc aacctttaag tgctatggcg 2400 tttctgccac taagttgaat gatctttgct tctccaatgt ctatgcagat tcttttgtag 2460 tcaagggaga tgatgtaaga caaatagcgc caggacaaac tggtgttatt gctgattata 2520 attataaatt gccagatgat ttcatgggtt gtgtccttgc ttggaatact aggaacattg 2580 atgctacttc aactggtaat tataattata aatataggta tcttagacat ggcaagctta 2640 ggccctttga gagagacata tctaatgtgc ctttctcccc tgatggcaaa ccttgcaccc 2700 cacctgctct taattgttat tggccattaa atgattatgg tttttacacc actactggca 2760 ttggctacea accttacaga gttgtagtac tttcttttga aettttaaat gcaecggcca 2820 cggtttgtgg accaaaatta tccactgacc ttattaagaa ccagtgtgtc aattttaatt 2880 ttaatggact cactggtact ggtgtgttaa ctccttcttc aaagagattt caaccatttc 2940 aacaatttgg ccgtgatgtt tctgatttca ctgattccgt tcgagatcct aaaacatctg 3000 aaatattaga catttcacct tgctcttttg ggggl:gtaag tgtaattaca cctggaacaa 3060 atgcttcatc tgaagttgct gttctatatc aagatgttaa ctgcactgat gtttctacag 3120 caattcatgc agatcaactc acaccagctt ggcgcatata ttctactgga aacaatgtat 3180 tccagactca ggcaggctgt cttataggag ctgagcatgt cgacacttct tatgagtgcg 3240 acattcctat tggagctggc atttgtgcta gttaccatac agtttcttta ttacgtagta 3300 ctagccaaaa atctattgtg gcttatacta tgtctttagg tgctgatagt tcaattgctt 3360 actctaataa caccattgct atacctacta acttttcaat tagcattact acagaagtaa 3420 tgcctgtttc tatggctaaa acctccgtag attgtaatat gtacatctgc ggagattcta 3480 ctgaatgtgc taatttgctt ctceaatatg gtagcttttg cacacaacta aatcgtgcac 3540 tctcaggtat tgctgctgaa caggatcgca acacacgtga agtgttcgct caagtcaaac 3600 aaatgtacaa aaccccaact ttgaaatatt ttggtggttt taatttttca caaatattac 3660 ctgaccctct aaagccaact aagaggtctt ttattgagga cttgctcttt aataaggtga 3720 cactcgctga tgctggcttc atgaagcaat atggcgaatg cctaggtgat attaatgcta 3780 gagatctcat ttgtgcgcag aagttcaatg gacttacagt gttgccacct ctgctcactg 3840 atgatatgat tgctgcctac actgctgctc tagttagtgg tactgccact gctggatgga 3900 catttggtgc tggcgctget cttcaaatac cttttgctat gcaaatggca tataggttca 3960 atggcattgg agttacccaa aatgttctct atgagaacca aaaacaaatc gccaaccaat 4020 ttaacaaggc gattagtcaa attcaagaat cacttacaac aacatcaact gcattgggca 4080 agctgcaaga cgttgttaac cagaatgctc aagcattaaa cacacttgtt aaacaactta 4140 gctctaattt tggtgcaatt tcaagtgtgc taaatgatat cctttcgcga cttgataaag 4200 fccgaggcgga ggtacaaatt gacaggttaa ttacaggcag acttcaaagc cttcaaacct 4260 atgtaacaca acaactaatc agggctgctg aaatcagggc ttctgctaat cttgctgcta 4320 ctaaaatgtc tgagtgtgtt cttggacaat caaaaagagt tgacttttgt ggaaagggct 4380 accaccttat gtccttccca caagcagccc cgcatggtgt tgtcttccta catgtcacgt 4440 atgtgccatc ccaggagagg aacttcacca cagcgccagc aatttgtcat gaaggcaaag 4500 catacttccc tcgtgaaggt gtttttgtgt ttaatggcac ttcttggttt attacacaga 4560 ggaacttctt ttctccacaa ataattacta cagacaatac atttgtctca ggaaattgtg 4620 atgtcgttat tggcatcatt aacaacacag tttatgatcc tctgcaacct gagcttgact 4680 cattcaaaga agagctggac aagtacttca aaaatcatac atcaccagat gttgattttg 4740 gcgacatttc aggeattaac gcttctgtcg teaacattca aaaagaaatt gaccgcctca 4800 atgaggtcgc taaaaattta aatgaatcac tcattgacct tcaagaactg ggaaaatatg 4860 agcaatatat taaatggcct ctcgacgaac aaaaactcat ctcagaagag gatctgaatg 4920 ctgtgggcca ggacacgcag gaggtcatcg tggtgccaca ctccttgccc tttaaggtgg 4980 tggtgatctc agccatcctg gccctggtgg tgctcaccat catctccctt atcatcctca 5040 tcatgctttg gcagaagaag ccacgttagg cggccgctcg agtgctagca ccaagggccc 5X00 cagcgtgttc cccctggccc ccagcagcaa gagcaccagc ggcggcacag ccgccctggg 5160 ctgcctggtg aaggactact tccccgagcc cgtgaccgtg agctggaaca gcggcgcctt 5220 gaccagcggc gtgcacacct tccccgccgt gctgcagagc agcggcctgt acagcctgag 5280 cagcgtggtg accgtgccca gcagcagcct gggcacccag acctacatct gcaacgtgaa 5340 ccacaagccc agcaacacca aggtggacaa acgcgtggag cccaagagct gcgacaagac 5400 ccacacctgc cccccctgcc ctgcccccga gctgctgggc ggaccctccg tgttcctgtt 5460 cccccccaag cccaaggaca ccctcatgat cagccggacc cccgaggtga cctgcgtggt 5520 ggtggacgtg agccacgagg accccgaggt gaagttcaac tggtacgtgg acggcgtgga 5580 ggtgcacaac gccaagacca agccccggga ggagcagtac aacagcacct accgggtggt 5640 gagcgtgctc accgtgctgc accaggactg gctgaacggc aaggagtaca agtgcaaggt 5700 gagcaacaag gccctgcctg cccccatcga gaagaccatc agcaaggcca agggccagcc 5760 ccgggagccc caggtgtaca ccctgccccc cagccgggag gagatgacca agaaccaggt 5820 gtccctcacc tgtctggtga agggcttcta ccccagcgac atcgccgtgg agtgggagag 5880 caacggccag cccgagaaca actacaagac caceccccct gtgctggaca gcgacggcag 5940 cttcttcctg tacagcaagc tcaccgtgga caagagccgg tggcagcagg gcaacgtgtt 6000 cagctgcagc gtgatgcacg aggccctgca caaccactac acccagaaga gcctgagcct 6060 gagccccggc aagtgataat ctagagggcc cgtttaaacc cgctgatcag cctcgactgt 6120 gccttctagt tgccagccat ctgttgtttg cccctccccc gtgccttcct tgaccctgga 6180 aggtgccact cccactgtcc tttcctaata aaatgaggaa attgcatcgc attgtctgag 6240 taggtgtcat tctattctgg ggggtggggt ggggcaggac agcaaggggg aggattggga 6300 agacaatagc aggcatgctg gggatgcggt gggctctatg gcttctgagg cggaaagaac 6360 cagetggggc tctagggggt atccccacgc gccctgtagc ggcgcattaa gcgcggcggg 6420 tgtggtggtt acgcgcagcg tgaccgctac acttgccagc gccctagcgc ccgctccttt 6480 cgctttcttc ccttcctttc tcgccacgtt cgccggcttt ccccgtcaag ctctaaatcg 6540 ggggctccct ttagggttcc gatttagtgc tttacggcac ctcgacccca aaaaacttga 6600 ttagggtgat ggttcacgta gtgggccatc gccctgatag acggtttttc gccctttgac 6660 gttggagtcc acgttcttta atagtggact cttgttccaa actggaacaa cactcaaccc 6720 tatctcggtc tattcttttg atttataagg gattttgccg atttcggcct attggttaaa 6780 aaatgagctg atttaacaaa aatttaacgc gaattaattc tgtggaatgt gtgtcagtta 6840 gggtgtggaa agtccccagg ctccccagca ggcagaagta tgcaaagcat gcatctcaat 6900 tagtcagcaa ccaggtgtgg aaagtcccca ggctccccag caggcagaag tatgcaaagc 6960 atgcatctca attagtcagc aaccatagtc ccgcccctaa ctccgcccat cccgccccta 7020 actccgccca gttccgccca ttctccgccc catggctgac taattttttt tatttatgca 7080 gaggccgagg ccgcctctgc ctctgagcta ttccagaagt agtgaggagg cttttttgga 7140 ggcctaggct tttgcaaaaa gctcccggga gcttgtatat ccattttcgg atctgatcaa 7200 gagacaggat gaggatcgtt tcgcatgatt gaacaagatg gattgcacgc aggttctccg 7260 gccgcttggg tggagaggct attcggctat gactgggcac aacagacaat cggctgctct 7320 gatgccgccg tgttccggct gtcagcgcag gggcgcccgg ttctttttgt caagaccgac 7380 ctgtccggtg ccctgaatga actgcaggac gaggcagcgc ggctatcgtg gctggccacg 7440 acgggcgttc; cttgcgcagc tgtgctcgac gttgtcactg aagcgggaag ggactggctg 7500 ctattgggcg aagtgccggg gcaggatctc ctgtcatctc accttgctcc tgccgagaaa 7560 gtatccatca tggctgatgc aatgcggcgg ctgcatacgc ttgatccggc tacctgccca 7620 ttcgaccacc aagcgaaaca tcgcatcgag cgagcacgta ctcggatgga agccggtctt 7680 gtcgatcagg atgatctgga cgaagagcat caggggctcg cgccagccga actgttcgcc 7740 aggctcaagg cgcgcatgcc cgacggcgag gatetcgtcg tgaeecatgg egatgeetge 7800 ttgccgaata tcatggtgga aaatggccgc ttttctggat teategaetg tggccggctg 7860 ggtgtggcgg accgctatca ggacatagcg ttggctaccc gtgatattgc tgaagagett 7920 ggcggcgaat gggetgaeeg cttcctcgtg etttaeggta tcgccgctcc egattegeag 7980 cgcatcgcct tctatcgcct tettgaegag ttettetgag cgggactctg gggttcgaaa 8040 tgaccgacca agcgacgccc aacctgccat cacgagattt cgattccacc gccgccttct 8100 atgaaaggtt gggettegga atcgttttcc gggacgccgg ctggatgate ctccagcgcg 8160 gggateteat getggagttc ttcgcccacc ccaaettgtt tattgeaget tataatggtt 8220 acaaataaag caatagcatc acaaatttca caaataaagc atttttttea etgeatteta 8280 gttgtggttt gtccaaactc atcaatgtat cttatcatgt ctgtataccg tcgacctcta 8340 getagagett ggcgtaatca tggtcatagc tgtttcctgt gtgaaattgt tatccgctca 8400 caattccaca caacatacga gccggaagca taaagtgtaa agcctggggt gcetaatgag 8460 tgagetaaet cacattaatt gcgttgcgct cactgcccgc tttccagtcg ggaaacctgt 8520 cgtgccagct gcattaatga atcggccaac gcgcggggag aggeggtttg cgtattgggc 8580 gctcttccgc ttcctcgctc actgactcgc tgegeteggt egtteggetg eggegagegg 8640 tateagetea ctcaa&ggcg gtaatacggt tatccacaga atcaggggat aaegeaggaa 8700 agaacatgtg agcaaaaggc cagcaaaagg ccaggaaccg taaaaaggcc gcgttgctgg 8760 cgtttttcca taggctccgc ccccctgacg agcatcacaa aaatcgacgc tcaagtcaga 8820 ggtggcgaaa cccgacagga ctataaagat accaggcgtt tccccctgga agctccctcg 8880 tgcgctctcc tgttccgacc ctgccgctta ccggatacct gtccgccttt ctcccttcgg 8940 gaagcgtgge gctttctcat agctcacgct gtaggtatct cagttcggtg taggtcgttc 9000 gctccaagct gggctgtgtg cacgaacccc ccgttcagcc cgaccgctgc gccttatccg 9060 gtaactatcg tcttgagtcc aacccggtaa gacacgactt atcgccactg gcagcagcca 9120 ctggtaacag gattagcaga gcgaggtatg taggcggtgc tacagagttc ttgaagtggt 9180 ggcctaacta cggctacaet agaagaacag tatttggtat ctgcgctctg ctgaagccag 9240 ttaccttcgg aaaaagagtt ggtagctctt gatccggcaa acaaaccacc gctggtagcg 9300 gtttttttgt ttgcaagcag cagattacgc gcagaaaaaa aggatctcaa gaagatcctt 9360 tgatcttttc tacggggtct gacgctcagt ggaacgaaaa ctcacgttaa gggattttgg 9420 tcatgagatt atcaaaaagg atcttcacct agatcctttt aaattaaaaa tgaagtttta 9480 aatcaatcta aagtatatat gagtaaactt ggtctgacag ttaccaatgc ttaatcagtg 9540 aggcacctat ctcagcgatc tgtctatttc gttcatccat agttgcctga ctccccgtcg 9600 tgtagataac tacgatacgg gagggcttac catctggccc cagtgctgca atgataccgc 9660 gagacccacg ctcaccggct ccagatttat cagcaataaa ccagccagcc ggaagggccg 9720 agcgcagaag tggtcctgca actttatccg cctccatcca gtctattaat tgttgccggg 9780 aagctagagt aagtagttcg ccagttaata gtttgcgcaa cgttgttgcc attgctacag 9840 gcatcgtggt gtcacgctcg tcgtttggta tggcttcatt cagctccggt tcccaacgat 9900 caaggcgagt tacatgatcc cccatgttgt gcaaaaaagc ggttagctcc ttcggtcctc 9960 cgatcgttgt cagaagtaag ttggccgcag tgttatcact catggttatg gcagcactgc 10020 ataattctct tactgtcatg ccatccgtaa gatgcttttc tgtgactggt gagtactcaa 10080 ccaagtcatt ctgagaatag tgtatgcggc gaccgagttg ctcttgcccg gcgtcaatac 10140 gggataatac cgcgccacat agcagaactt taaaagtgct catcattgga aaacgttctt 10200 cggggcgaaa actctcaagg atcttaccgc tgttgagatc cagttcgatg taacccactc 10260 gtgcacccaa ctgatcttca gcatctttta ctttcaccag cgtttctggg tgagcaaaaa 10320 caggaaggca aaatgccgca aaaaagggaa taagggcgac acggaaatgt tgaatactca 10380 tactctfccct ttttcaatat tattgaagca tttatcaggg ttattgtctc atgagcggat 10440 acatatttga atgtatttag aaaaataaac aaataggggt tccgcgcaca tttccccgaa 10500 aagtgccacc tgacg 10515 <210> 142 <211 >8777 <212> DNA <213> Artificial <220> <223> Vector plg-C909-Ckappa <220> <221 > misc_feature <222> (1328)..(3860) <223> Stuffer <400> 142 tcgacggatc gggagatctc ccgatcccct atggtgcact ctcagtacaa tctgctctga 60 tgccgcatag ttaagccagt atctgctccc tgcttgtgtg ttggaggtcg ctgagtagtg 120 cgcgagcaaa atttaagcta caacaaggca aggcttgacc gacaattgtt aattaacatg 180 aagaatctgc ttagggttag gegttttgcg ctgcttcgct aggtggtcaa tattggccat 240 tagccatatt attcattggt tatatagcat aaatcaatat tggctattgg ccattgeata 300 cgttgtatcc atatcataat atgtacattt atattggctc atgtccaaca ttaccgccat 360 gttgacattg attattgact agttattaat agtaatcaat tacggggtca ttagttcata 420 gcccatatat ggagttccgc gttacataac ttacggtaaa tggcccgcct ggctgaccgc 480 ccaacgaccc ccgcccattg acgtcaataa tgacgtatgt tcccatagta acgccaatag 540 ggactttcca ttgacgtcaa tgggtggagt atttacggta aactgcccac ttggcagtac 600 atcaagtgta tcatatgcca agtacgcccc ctattgacgt caatgacggt aaatggcccg 660 cctggcatta tgcccagtac atgaccttat gggactttcc tacttggcag tacatctacg 720 tattagtcat cgctattacc atggtgatgc ggttttggca gtacatcaat gggcgtggat 780 agcggtttga ctcacgggga tttccaagtc tccaccccat tgacgtcaat gggagtttgt 840 tttggcacca aaatcaacgg gactttccaa aatgtcgtaa caactccgcc ccattgacgc 900 aaatgggcgg taggcgtgta cggtgggagg tctatataag cagagctcgt ttagtgaacc 960 gtcagatcgc ctggagacgc catccacgct gttttgacct ccatagaaga caccgggacc 1020 gatccagcct ccgcggccgg gaacggtgca ttggaatcga tgactctctt aggtagcctt 1080 gcagaagttg gtcgtgaggc actgggcagg taagtatcaa ggttacaaga caggtttaag 1140 gagatcaata gaaactgggc ttgtcgagac agagaagact cttgcgtttc tgataggcac 1200 ctattggtct tactgacatc cactttgcct ttctctccac aggtgtccac tcccagttca 1260 attacagctc gccaccatgc ggctgcccgc ccagctgctg ggccttctca tgctgtgggt 1320 gcccgcctcg agatctatcg atgcatgcca tggtaccaag cttgccacca tgagcagcag 1380 ctcttggctg ctgctgagcc tggtggccgt gacagccgcc cagagcacca tcgaggagca 1440 ggccaagacc ttcctggaca agttcaacca cgaggccgag gacctgttct accagagcag 1500 cctggccagc tggaactaca acaccaacat caccgaggag aacgtgcaga acatgaacaa 1560 cgccggcgac aagtggagcg ccttcctgaa ggagcagagc acactggccc agatgtaccc 1620 cctgcaggag atccagaacc tgaccgtgaa gctgcagctg caggccctgc agcagaacgg 1680 cagcagcgtg ctgagcgagg acaagagcaa gcggctgaac accatcctga acaccatgtc 1740 caccatctac agcaccggca aagtgtgcaa ccccgacaac ccccaggagt gcctgctgct 1800 ggagcccggc ctgaacgaga tcatggccaa cagcctggac tacaacgagc ggctgtgggc 1860 ctgggagagc tggcggagcg aagtgggcaa gcagctgcgg cccctgtacg aggagtacgt 1920 ggtgctgaag aacgagatgg ccagggccaa ccactacgag gactacggcg actactggag 1980 aggcgactac gaagtgaacg gcgtggacgg ctacgactac agcagaggcc agctgatcga 2040 ggacgtggag cacacetteg aggagatcaa gectctgtac gagcacctgc acgcctacgt 2100 gcgggccaag ctgatgaacg cctaccccag ctacatcagc cccatcggct gcctgcccgc 2160 ccacctgctg ggcgacatgt ggggccggtt ctggaccaac ctgtacagcc tgaccgtgcc 2220 cttcggccag aagcccaaca tcgacgtgac cgacgccatg gtggaccagg cctgggacgc 2280 ccagcggatc ttcaaggagg ccgagaagtt cttcgtgagc gtgggcctgc ccaacatgac 2340 ccagggcttt tgggagaaca gcatgctgac cgaccccggc aatgtgcaga aggccgtgtg 2400 ccaccccacc gcctgggacc tgggcaaggg cgacttccgg atcctgatgt gcaccaaagt 2460 gaccatggac gacttcctga ccgcccacca cgagatgggc cacatccagt acgacatggc 2520 ctacgccgcc cagcccttcc tgctgcggaa cggcgccaac gagggctttc acgaggccgt 2580 gggcgagatc atgagcctga gcgccgccac ccccaagcac ctgaagagca tcggcctgct 2640 gagccccgac ttccaggagg acaacgagac cgagatcaac ttcctgctga agcaggccct 2700 gaccatcgtg ggcaccctgc ccttcaccta catgctggag aagtggcggt ggatggtgtt 2760 taagggcgag atccccaagg accagtggat gaagaagtgg tgggagatga agcgggagat 2820 cgtgggcgtg gtggagcccg tgccccacga cgagacctac tgcgaccccg ccagcctgtt 2880 ccacgtgagc aacgactact ccttcatccg gtactacacc cggaccctgt accagttcca 2940 gttccaggag gccctgtgcc aggccgccaa gcacgagggc cccctgcaca agtgcgacat 3000 cagcaacagc accgaggccg gacagaaact gttcaacatg ctgcggctgg gcaagagcga 3060 gccctggacc ctggccctgg agaatgtggt gggcgccaag aacatgaatg tgcgccccct 3120 gctgaactac ttcgagcccc tgttcacctg gctgaaggac cagaacaaga acagcttcgt 3180 gggctggagc accgactgga gcccctacgc cgaccagagc atcaaagtgc ggatcagcct 3240 gaagagcgcc ctgggcgaca aggcctacga gtggaacgac aacgagatgt acctgttccg 3300 gagcagcgtg gcctatgcca tgcggcagta cttcctgaaa gtgaagaacc agatgatcct 3360 gttcggcgag gaggacgtga gagtggccaa cctgaagccc cggatcagct tcaacttctt 3420 cgtgaccgcc cccaagaacg tgagcgacat catcccccgg accgaagtgg agaaggccat 3480 ccggatgagc cggagccgga tcaacgacgc cttccggctg aacgacaact ccctggagtt 3540 cctgggcatc cagcccaccc tgggccctcc caaccagccc cccgtgagca tctggctgat 3600 cgtgtttggc gtggtgatgg gcgtgatcgt ggtgggaatc gtgatcctga tcttcaccgg 3660 catccgggac cggaagaaga agaacaaggc ccggagcggc gagaacccct acgccagcat 3720 cgatatcagc aagggcgaga acaaccccgg cttccagaac accgacgacg tgcagaccag 3780 cttctgataa tctagaacga gctcgaattc gaagcttctg cagacgcgtc gacgtcatat 3840 ggatccgata tcgccgtggc ggccgcaccc agcgtgttca tcttcccccc ctccgacgag 3900 cagctgaaga gcggcaccgc cagcgtggtg tgcatgctga acaacttcta cccccgggag 3960 gccaaggtgc agtggaaggt ggacaacgcc ctgcagagcg gcaacagcca ggagagcgtg 4020 accgagcagg acagcaagga ctccacctac agcctgagca gcaccctcac cctgagcaag 4080 gccgactacg agaageacaa ggtgtacgcc tgcgaggtga cccaccaggg cctgagcagc 4X40 cccgtgacca agagcttcaa ccggggcgag tgttaataga cttaagttta aaccgetgat 4200 cagcctcgac tgtgccttct agttgccagc catctgttgt ttgcccctcc cccgtgcctt 4260 ccttgaccct ggaaggtgcc actcccactg tcctttccta ataaaatgag gaaattgcat 4320 cgcattgtct gagtaggtgt cattctattc tggggggtgg ggtggggcag gacagcaagg 4380 gggaggattg ggaagacaat agcaggcatg ctggggatgc ggtgggctct atggcttctg 4440 aggcggaaag aaccagctgg ggctctaggg ggtatcccca cgcgccctgt agcggcgcat 4500 taagcgcggc gggtgtggtg gttacgcgca gcgtgaccgc tacacttgcc agcgccctag 4560 cgcccgctcc tttcgctttc ttcccttcct ttctcgccac gttcgccggc tttccccgtc 4620 aagctctaaa tcgggggctc cctttagggt tccgatttag tgctttacgg cacctcgacc 4680 ccaaaaaaet tgattagggt gatggttcac gtagtgggcc atcgccctga tagacggttt 4740 ttcgcccttt gacgttggag tccacgttct ttaatagtgg actcttgttc caaactggaa 4800 caacactcaa ccctatctcg gtctattctt ttgatttata agggattttg gccatttcgg 4860 cctattggtt aaaaaatgag ctgatttaac aaaaatttaa cgcgaattaa ttctgtggaa 4920 tgtgtgtcag ttagggtgtg gaaagtcccc aggctcccca gcaggcagaa gtatgcaaag 4980 catgcatctc aattagtcag caaccaggtg tggaaagtcc ccaggctccc cagcaggcag 5040 aagtatgeaa agcatgcatc tcaattagtc agcaaccata gtcccgcccc taactccgcc 5100 catcccgccc ctaactccgc ccagttccgc ccattctccg ccccatggct gactaatttt 5160 ttttatttat gcagaggccg aggccgcctc tgcctetgag ctattccaga agtagtgagg 5220 aggctttttt ggaggcctag gcttttgcaa aaagctcccg ggagcttgta tatccatttt 5280 cggatctgat cagcacgtga tgaaaaagcc tgaactcacc gcgacgtctg tcgagaagtt 5340 tctgatcgaa aagttcgaca gcgtctccga cctgatgcag ctctcggagg gcgaagaatc 5400 tcgtgctttc agcttcgatg taggagggcg tggatatgtc ctgcgggtaa atagctgcgc 5460 cgatggtttc tacaaagatc gttatgttta tcggcacttt gcatcggccg cgctcccgat 5520 tccggaagtg cttgacattg gggaattcag cgagagcctg acctattgca tctcccgccg 5580 tgcacagggt gtcacgttgc aagacctgcc tgaaaccgaa ctgcccgctg ttctgcagcc 5640 ggtcgcggag gccatggatg cgatcgctgc ggccgatctt agccagacga gcgggttcgg 5700 cccattcgga ccacaaggaa tcggtcaata cactacatgg cgtgatttca tatgcgcgat 5760 tgctgatccc catgtgtatc actggcaaac tgtgatggac gacaccgtca gtgcgtccgt 5820 cgcgcaggct ctcgatgagc tgatgctttg ggccgaggac tgccccgaag tccggcacct 5880 cgtgcacgcg gatttcggct ccaacaatgt cctgacggac aatggccgca taacagcggt 5940 cattgactgg agcgaggcga tgttcgggga ttcccaatac gaggtcgcca acatcttctt 6000 ctggaggccg tggttggctt gtatggagca gcagacgcgc tacttcgagc ggaggcatcc 6060 ggagcttgca ggatcgccgc ggctccgggc gtatatgctc cgcattggtc ttgaccaact 6120 ctatcagagc ttggttgacg gcaatttcga tgatgcagct tgggcgcagg gtcgatgcga 6180 cgcaatcgtc cgatccggag ccgggactgt cgggcgtaca caaatcgccc gcagaagcgc 6240 ggccgtctgg accgatggct gtgtagaagt actcgccgat agtggaaacc gacgccccag 6300 cactcgtccg agggcaaagg aatagcacgt gctacgagat ttcgattcca ccgccgcctt 6360 ctatgaaagg ttgggcttcg gaatcgtttt ccgggacgcc ggctggatga tcctccagcg 6420 cggggatctc atgctggagt tcttcgccca ccccaacttg tttattgcag cttataatgg 6480 ttacaaataa agcaatagca tcacaaattt cacaaataaa gcattttttt cactgcattc 6540 tagttgtggt ttgtccaaac tcatcaatgt atcttatcat gtctgtatac cgtcgaccfcc 6600 tagctagagc ttggcgtaat catggtcata gctgtttcct gtgtgaaatt gttatccgct 6660 cacaattcca cacaacatac gagccggaag cataaagtgt aaagcctggg gtgcctaatg 6720 agtgagctaa ctcacattaa ttgcgttgcg ctcactgccc gctttccagt egggaaacct 6780 gtcgtgccag ctgcattaat gaatcggcca acgcgcgggg agaggcggtt tgcgtattgg 6840 gcgctcttcc gcttcctcgc tcactgactc gctgcgetcg gtcgttcggc tgcggcgagc 6900 ggtatcagct cactcaaagg cggtaatacg gttatccaca gaatcagggg ataacgcagg 6960 aaagaacatg tgagcaaaag gccagcaaaa ggccaggaac cgtaaaaagg ccgcgttgct 7020 ggcgrtttttc cataggctcc gcccccctga cgagcatcac aaaaatcgac gctcaagtca 7080 gaggtggcga aacccgacag gactataaag ataccaggcg tttccccctg gaagctccct 7140 cgtgcgctct cctgttccga ccctgccgct taccggatac ctgtccgcct ttctcccttc 7200 gggaagcgtg gcgctttctc atagctcacg ctgtaggtat ctcagttcgg tgtaggtcgt 7260 tcgctccaag ctgggctgtg tgcacgaacc ccccgttcag cccgaccgct gcgccttatc 7320 cggtaactat cgtcttgagt ccaacccggt aagacacgac ttatcgccac tggcagcagc 7380 cactggtaac aggattagca gagcgaggta tgtaggcggt gctacagagt tcttgaagtg 7440 gtggcctaac tacggctaca ctagaagaac agtatttggt atctgcgctc tgctgaagcc 7500 agttaccttc ggaaaaagag ttggtagctc ttgatccggc aaacaaacca ccgctggtag 7560 cggttttttt gtttgcaagc agcagattac gcgcagaaaa aaaggatctc aagaagatcc 7620 tttgatcttt tctacggggt ctgacgctca gtggaacgaa aacteacgtt aagggatttt 7680 ggtcatgaga ttatcaaaaa ggatcttcac ctagatcctt ttaaattaaa aatgaagttt 7740 taaatcaatc taaagtatat atgagtaaac ttggtctgac agttaccaat gcttaatcag 7800 tgaggcacct atctcagcga tctgtctatt tcgttcatcc atagttgcct gactccccgt 7860 cgtgtagata actacgatac gggagggctt accatctggc cccagtgctg caatgatacc 7920 gcgagaccca cgctcaccgg ctccagattt atcagcaata aaccagccag ccggaagggc 7980 cgagcgcaga agtggtcctg caactttatc cgcctccatc cagtctatta attgttgccg 8040 ggaagctaga gtaagtagtt cgccagttaa tagtttgcgc aacgttgttg ccattgctac 8100 aggcatcgtg gtgtcacgct cgtcgtttgg tatggcttca ttcagctccg gttcccaacg 8160 atcaaggcga gttacatgat cccccatgtt gtgcaaaaaa gcggttagct ccttcggtcc 8220 tccgatcgtt gtcagaagta agttggccgc agtgttatca ctcatggtta tggcagcact 8280 gcataattct cttactgtca tgccatccgt aagatgcttt tctgtgactg gtgagtactc 8340 aaccaagtca ttctgagaat agtgtatgcg gcgaccgagt tgctcttgcc cggcgtcaat 8400 acgggataat accgcgccac atagcagaac tttaaaagtg ctcatcattg gaaaacgttc 8460 ttcggggcga aaactctcaa ggatcttacc gctgttgaga tccagttcga tgtaacccac 8520 tcgtgcaccc aactgatctt cagcatcttt tactttcacc agcgtttctg ggtgagcaaa 8580 aacaggaagg caaaatgccg caaaaaaggg aataagggcg acacggaaat gttgaatact 8640 catactettc ctttttcaat attattgaag catttatcag ggttattgtc tcatgagcgg 8700 atacatattt gaatgtattt agaaaaataa acaaataggg gttccgcgca catttccccg 8760 aaaagtgcca cctgacg 8777 <210> 143 <211 >8792 <212> DNA <213> Artificial <220> <223> Vector plg-C910-Clambda <220> <221 > misc_feature <222> (1330)..(3869) <223> Stuffer <400> 143 tcgacggatc gggagatcto ccgatcccct atggtgcact ctcagtacaa totgotctga 60 tgccgcatag ttaagccagt atctgctccc tgcttgtgtg ttggaggtcg ctgagtagtg 120 cgcgagcaaa atttaagcta caacaaggca aggcttgacc gacaattgtt aattaacatg 180 aagaatctgc ttagggttag gcgttttgcg ctgcttcgct aggtggtcaa tattggccat 240 tagccatatt attcattggt tatatagcat aaatcaatat tggctattgg ccattgcata 300 cgttgtatcc atatcataat atgtacattt atattggctc atgtccaaca ttaccgccat 360 gttgacattg attattgact agttattaat agtaatcaat tacggggtca ttagttcata 420 gcccatatat ggagttccgc gttacataac ttacggtaaa tggcccgcct ggctgaccgc 480 ccaacgaccc ccgcccattg acgtcaataa tgacgtatgt tcceatagta acgccaatag 540 ggactttcca ttgacgtcaa tgggtggagt atttacggta aactgcccac ttggcagtac 600 atcaagtgta tcatatgcca agtacgcccc ctattgacgt caatgacggt aaatggcccg 660 cctggcatta tgcccagtac atgaccttat gggactttcc tacttggcag tacatctacg 720 tattagtcat cgctattacc atggtgatgc ggttttggca gtacatcaat gggcgtggat 780 agcggtttga ctcacgggga tttccaagtc tccaccccat tgacgfccaat gggagtttgt 840 tttggcacca aaatcaacgg gactttccaa aatgtcgtaa caactccgcc ccattgacgc 900 aaatgggcgg taggcgtgta cggtgggagg tctatataag cagagctcgt ttagtgaacc 960 gtcagatcgc ctggagacgc catccacgct gttttgacct ccatagaaga caccgggacc 1020 gatccagcct ccgcggccgg gaacggtgca ttggaatcga tgactctctt aggtagcctt 1080 gcagaagttg gtcgtgaggc actgggcagg taagtatcaa ggttacaaga caggtttaag 1140 gagatcaata gaaactgggc ttgtcgagac agagaagact cttgcgtttc tgataggcac 1200 ctattggtct tactgacatc cactttgcct ttctctccac aggtgtccac tcccagttca 1260 attacagctc gccaccatgc ggttctccgc tcagctgctg ggccttctgg tgctgtggat 1320 tcccggcgtc tcgagatcta tcgatgcatg ccatggtacc aagcttgcca ccatgagcag 1380 cagctcttgg ctgctgctga gcctggtggc cgtgacagcc gcccagagca ccatcgagga 1440 gcaggccaag accttcctgg acaagttcaa ccacgaggcc gaggacctgt tctaecagag 1500 cagcctggcc agctggaact acaacaccaa eatcaccgag gagaacgtgc agaacatgaa 1560 caacgccggc gacaagtgga gcgccttcct gaaggagcag agcacactgg cccagatgta 1620 ccccctgcag gagatccaga acctgaccgt gaagctgcag ctgcaggccc tgcageagaa 1680 cggcagcagc gtgctgagcg aggacaagag caagcggctg aacaccatcc tgaacaccat 1740 gtccaccatc tacagcaccg gcaaagtgtg caaccccgac aacccccagg agtgcctgct 1800 gctggagccc ggcctgaacg agatcatggc caacagcctg gactacaacg agcggctgtg 1860 ggcctgggag agctggcgga gcgaagtggg caagcagctg cggcccctgt acgaggagta 1920 cgtggtgctg aagaacgaga tggccagggc caaccactac gaggactacg gcgactactg 1980 gagaggcgac tacgaagtga acggcgtgga cggctacgac tacagcagag gccagctgat 2040 cgaggacgtg gagcacacct tcgaggagat caagcctctg tacgagcacc tgcacgccta 2100 cgtgcgggcc aagctgatga acgcctaccc cagctacatc agccccatcg gctgcctgcc 2160 cgcccacctg ctgggcgaca tgtggggccg gttctggacc aacctgtaca gcctgaccgt 2220 gcccttcggc cagaagccca acatcgacgt gaccgacgcc atggtggacc aggcctggga 2280 cgcccagcgg atcttcaagg aggccgagaa gttcttcgtg agcgtgggcc tgcccaacat 2340 gacccagggc ttttgggaga acagcatgct gaccgacccc ggcaatgtgc agaaggccgt 2400 gtgccacccc accgcctggg acctgggcaa gggcgacttc cggatcctga tgtgcaccaa 2460 agtgaccatg gacgacttcc tgaccgccca ccacgagatg ggccacatcc agtacgacat 2520 ggcctacgcc gcccagccct tcctgctgcg gaacggcgcc aacgagggct ttcacgaggc 2580 cgtgggcgag atcatgagec tgagcgccgc cacccccaag cacctgaaga gcatcggcct 2640 gctgagcccc gacttccagg aggacaacga gaeegagate aacttcctgc tgaageagge 2700 cctgaccatc gtgggcaccc tgcccttcac ctacatgctg gagaagtgge ggtggatggt 2760 gtttaagggc gagatcccca aggaccagtg gatgaagaag tggtgggaga tgaagcggga 2820 gatcgtgggc gtggtggagc ccgtgcccca cgacgagacc tactgcgacc ccgccagcct 2880 gttccacgtg ageaaegaet actccttcat ccggtactac acccggaccc tgtaccagtt 2940 ccagttccag gaggccctgt gccaggccgc caagcacgag ggccccctgc aeaagtgega 3000 catcagcaac agcaccgagg ccggacagaa actgttcaac atgetgegge tgggcaagag 3060 cgagccctgg accctggccc tggagaatgt ggtgggcgcc aagaacatga atgtgcgccc 3120 cctgctgaac taettegage ccctgttcac ctggctgaag gaccagaaca agaaeagett 3180 cgtgggctgg agcaccgact ggagccccta cgccgaccag agcatcaaag tgcggatcag 3240 cctgaagagc gccctgggcg acaaggccta egagtggaae gaeaaegaga tgtacctgtt 3300 ccggagcagc gtggcctatg ccatgcggca gtacttcctg aaagtgaaga accagatgat 3360 cctgttcggc gaggaggaeg tgagagtggc caacctgaag ccccggatca gcttcaactt 3420 cttcgtgacc gcccccaaga aegtgagega catcatcccc cggaccgaag tggagaagge 3480 catccggatg agccggagcc ggatcaacga cgccttccgg etgaaegaea actccctgga 3540 gttcctgggc atccagceca ccctgggccc tcccaaccag ccccccgtga geatetgget 3600 gatcgtgttt ggcgtggtga tgggcgtgat cgtggtggga atcgtgatcc tgatetteae 3660 cggcatccgg gaeeggaaga agaagaacaa ggcccggagc ggcgagaacc cctacgccag 3720 catcgatatc agcaagggcg agaacaaccc cggcttccag aacaccgacg aegtgeagae 3780 cagcttctga taatctagaa egagetegaa ttegaagett ctgcagacgc gtegaegtea 3840 tatggateeg atatcgccgt ggcggccgca ggccagccca aggccgctcc cagcgtgacc 3900 ctgttccccc cctcctccga ggagctgcag gccaacaagg ccaccetggt gtgeetcatc 3960 agcgacttct accctggcgc cgtgaccgtg gcctggaagg ccgacagcag ccccgtgaag 4020 gccggcgtgg agaccaccac ccccagcaag cagagcaaca acaagtacgc cgccagcagc 4080 tacctgagcc tcacccccga gcagtggaag agccaccgga gctacagctg ccaggtgacc 4140 cacgagggca gcaccgtgga gaagaccgtg gcccccaccg agtgcagcta atagacttaa 4200 gtttaaaccg ctgatcagcc tcgactgtgc cttctagttg ccagccatct gttgtttgcc 4260 cctcccccgt gccttccttg accctggaag gtgccactcc cactgtcctt tcctaataaa 4320 atgaggaaat tgcatcgcat tgtctgagta ggtgtcattc tattctgggg ggtggggtgg 4380 ggcaggacag caagggggag gattgggaag acaatagcag gcatgctggg gatgcggtgg 4440 gctctatggc ttetgaggcg gaaagaacca gctggggctc tagggggtat ccccacgcge 4500 cctgtagcgg cgcattaagc gcggcgggtg tggtggttac gcgcagcgtg accgctacac 4560 ttgccagegc cctagcgccc gctcctttcg ctttcttccc ttcctttctc gccacgttcg 4620 ccggctttcc ecgtcaagct etaaatcggg ggctcccttt agggttecga tttagtgctt 4680 tacggcacct cgaccccaaa aaacttgatt agggtgatgg ttcacgtagt gggccatcgc 4740 cctgatagac ggtttttcgc cctttgacgt tggagtccac gttctttaat agtggactct 4800 tgttccaaac tggaacaaca ctcaacccta tctcggtcta ttcttttgat ttataaggga 4860 ttttggccat fcfccggcctat tggttaaaaa atgagctgat ttaacaaaaa tttaacgcga 4920 attaattctg tggaatgtgt gtcagttagg gtgtggaaag tccccaggct ccccagcagg 4980 cagaagtatg caaagcatgc atctcaatta gtcagcaacc aggtgtggaa agtccccagg 5040 ctccccagca ggcagaagta tgcaaagcat gcatctcaat tagtcagcaa ccatagtccc 5100 gcccctaact ccgcccatcc cgcccctaac tccgcccagt tccgcccatt ctccgcccca 5160 tggctgacta atttttttta tttatgcaga ggccgaggcc gcctctgcct ctgagctatt 5220 ccagaagtag tgaggaggct tttttggagg cctaggcttt tgcaaaaagc tcccgggagc 5280 ttgtatatcc attttcggat ctgatcagca cgtgatgaaa aagcctgaac tcaccgcgac 5340 gtctgtcgag aagtttctga tcgaaaagtt cgacagcgtc tccgacctga tgcagctctc 5400 ggagggcgaa gaatctcgtg ctttcagctt cgatgtagga gggcgtggat atgtcctgcg 5460 ggtaaatagc tgcgccgatg gtttctacaa agatcgttat gtttatcggc actttgcatc 5520 ggccgcgctc ccgattccgg aagtgcttga cattggggaa ttcagcgaga gcctgaccta 5580 ttgcatctcc cgccgtgcac agggtgtcac gttgcaagac ctgcetgaaa ccgaactgcc 5640 cgctgttctg cagccggtcg cggaggccat ggatgcgatc gctgcggccg atcttagcca 5700 gacgagcggg ttcggcccat tcggaccgca aggaatcggt caatacacta catggcgtga 5760 tttcatatgc gcgattgctg atccccatgt gtatcactgg caaactgtga tggacgacac 5820 cgtcagtgcg tccgtcgcgc aggctctcga tgagctgatg ctttgggccg aggactgccc 5880 cgaagtccgg cacctcgtgc acgcggattt cggctccaac aatgtcctga cggacaatgg 5940 ccgcataaca gcggtcattg actggagcga ggcgatgttc ggggattccc aatacgaggt 6000 cgccaacatc ttcttctgga ggccgtggtt ggcttgtatg gagcagcaga cgcgctactt 6060 cgagcggagg catccggagc ttgcaggatc gccgcggctc cgggcgtata tgctccgcat 6120 tggtcttgac eaactctatc agagcttggt tgacggcaat ttcgatgatg cagcttgggc 6180 gcagggtcga tgcgacgcaa tcgtccgatc cggagccggg actgtcgggc gtacacaaat 6240 cgcccgcaga agcgcggccg tctggaccga tggctgtgta gaagtactcg ccgatagtgg 6300 aaaccgacgc cccagcactc gtccgagggc aaaggaatag cacgtgctac gagatttcga 6360 ttccaccgcc gccttctatg aaaggttggg cttcggaatc gttttccggg acgccggctg 6420 gatgatcctc cagcgcgggg atctcatgct ggagttettc gcccacccca acttgtttat 6480 tgcagcttat aatggttaca aataaagcaa tagcatcaca aatttcacaa ataaagcatt 6540 tttttcactg cattctagtt gtggtttgtc caaactcatc aatgtatctt atcatgtctg 6600 tataccgtcg acctctagct agagcttggc gtaatcatgg tcatagctgt ttcctgtgtg 6660 aaattgttat ccgctcacaa ttccacacaa catacgagcc ggaagcataa agtgtaaagc 6720 ctggggtgcc taatgagtga gctaactcac attaattgcg ttgcgctcac tgcccgcttt 6780 ccagtcggga aacctgtcgt gccagctgca ttaatgaatc ggccaacgcg cggggagagg 6840 cggtttgcgt attgggcgct cttccgcttc ctcgctcact gactcgctgc gctcggtcgt 6900 tcggctgcgg cgagcggtat cagctcactc aaaggcggta atacggttat ccacagaatc 6960 aggggataac gcaggaaaga acatgtgagc aaaaggccag caaaaggcca ggaaccgtaa 7020 aaaggccgcg ttgctggcgt ttttccatag gctccgcccc cctgacgagc atcacaaaaa 7080 tcgacgctca agtcagaggt ggcgaaaccc gacaggacta taaagatacc aggcgtttcc 7140 ccctggaagc tccctcgtgc gctctectgt tccgaccctg ccgcttaccg gatacctgtc 7200 cgcctttctc ccttcgggaa gcgtggcgct ttctcatagc tcacgctgta ggtatctcag 7260 ttcggtgtag gtcgttcgct ccaagctggg ctgtgtgcac gaaccccccg ttcagcccga 7320 ccgctgcgcc ttatccggta actatcgtct tgagtccaac ccggtaagac acgacttatc 7380 gccactggca gcagccactg gtaacaggat tagcagagcg aggtatgtag gcggtgctac 7440 agagttcttg aagtggtggc ctaactacgg ctacactaga agaacagtat tfcggtatcfcg 7500 cgctctgctg aagccagtta ccttcggaaa aagagttggt agctcttgat ccggcaaaca 7560 aaccaccgct ggtagcggtt tttttgtttg caagcagcag attacgcgca gaaaaaaagg 7620 atctcaagaa gatcctttga tcttttctac ggggtctgac gctcagtgga acgaaaactc 7680 acgttaaggg attttggtca tgagattatc aaaaaggatc ttcacctaga tccttttaaa 7740 ttaaaaatga agttttaaat caatctaaag tatatatgag taaacttggt ctgacagtta 7800 ccaatgctta atcagtgagg cacctatctc agcgatctgt ctatttcgtt catccatagt 7860 tgcctgactc cccgtcgtgt agataactac gatacgggag ggcttaccat ctggccccag 7920 tgctgcaatg ataccgcgag acccacgctc accggctcca gatttatcag caataaacca 7980 gccagccgga agggccgagc gcagaagtgg tcctgcaact ttatccgcct ccatccagtc 8040 tattaattgt tgccgggaag ctagagtaag tagttcgcca gttaatagtt tgcgcaacgt 8100 tgttgccatt gctacaggca tcgtggftgtc acgctcgtcg tttggtatgg cttcattcag 8160 ctccggttcc caacgatcaa ggcgagttac atgatccccc atgttgtgca aaaaagcggt 8220 tagctccttc ggtcctccga tcgttgtcag aagtaagttg gccgcagtgt tatcactcat 8280 ggttatggca gcactgcata attctcttac tgtcatgcca tccgtaagat gcttttctgt 8340 gactggtgag tactcaacca agtcattctg agaatagtgt atgcggcgac cgagttgctc 8400 ttgcccggcg tcaatacggg ataataccgc gccacatagc agaactttaa aagtgctcat 8460 cattggaaaa cgttcttcgg ggcgaaaact ctcaaggatc ttaccgctgt tgagatccag 8520 ttcgatgtaa cccactcgtg cacccaactg atcttcagca tcttttactt tcaccagcgt 8580 ttctgggtga gcaaaaacag gaaggcaaaa tgccgcaaaa aagggaataa gggcgacacg 8640 gaaatgrttga atactcatac tcttcctttt tcaatattat tgaagcattt atcagggtta 8700 ttgtctcatg agcggataca tatttgaatg tatttagaaa aataaaeaaa taggggttec 8760 gcgcacattt ccccgaaaag tgccacctga cg 8792 <210> 144 <211> 23 <212> DNA <213> Artificial <220> <223> Primer 0K1 (HuVKIB) <400> 144 gacatccagw tgacccagtc tcc 23 <210> 145 <211> 23 <212> DNA <213> Artificial <220> <223> Primer 0K2 (HuVK2) <400> 145 gatgttgtga tgactcagtc tcc 23 <210> 146 <211> 23 <212> DNA <213> Artificial <220> <223> Primer 0K3 (HuVK2B2) <400> 146 gatattgtga tgacccagac tcc 23 <210> 147 <211> 23 <212> DNA <213> Artificial <220> <223> Primer 0K4 (HuVK3B) <400> 147 gaaattgtgw tgacrcagtc tcc 23 <210> 148 <211> 23 <212> DNA <213> Artificial <220> <223> Primer 0K5 (HuVK5) <400>148 gaaacgacac tcacgcagtc tcc 23 <210> 149 <211> 23 <212> DNA <213> Artificial <220> <223> Primer 0K6 (HuVK6) <400> 149 gaaattgtgc tgactcagtc tcc 23 <210> 150 <211 > 24 <212> DNA <213> Artificial <220> <223> Primer OCK (HuCK) <400> 150 acactctccc ctgttgaagc tctt 24 <210> 151 <211 > 23 <212> DNA <213> Artificial <220> <223> Primer OL1 (HuVLIA) <400> 151 cagtctgtgc tgactcagcc acc 23 <210> 152 <211> 23 <212> DNA <213> Artificial <220> <223> Primer OL1 (HuVLIB) <400> 152 cagtctgtgy tgacgcagcc gcc 23 <210> 153 <211> 23 <212> DNA <213> Artificial <220> <223> Primer OL1 (HuVLIC) <400> 153 cagtctgtcg tgacgcagcc gcc 23 <210> 154 <211> 20 <212> DNA <213> Artificial <220> <223> OL2 (HuVL2B) <400> 154 cagtctgccc tgactcagcc 20 <210> 155 <211> 23 <212> DNA <213> Artificial <220> <223> 0L3 (HuVL3A) <400> 155 tcctatgwgc tgactcagcc acc 23 <210> 156 <211 > 23 <212> DNA <213> Artificial <220> <223> 0L4 (HuVL3B) <400> 156 tcttctgagc tgactcagga ccc 23 <210> 157 <211> 20 <212> DNA <213> Artificial <220> <223> OL5 (HuVL4B) <400> 157 cagcytgtgc tgactcaatc 20 <210> 158 <211 > 23 <212> DNA <213> Artificial <220> <223> OL6 (HuVL5) <400> 158 caggctgtgc tgactcagcc gtc 23 <210> 159 <211> 23 <212> DNA <213> Artificial <220> <223> OL7 (HuVL6) <400> 159 aattttatgc tgactcagcc cca 23 <210> 160 <211> 23 <212> DNA <213> Artificial <220> <223> OL8 (HuVL7/8) <400> 160 cagrctgtgg tgacycagga gcc 23

<210> 161 <211> 23 <212> DNA <213> Artificial <220> <223> 0L9 (HuVL9) <400> 161 cwgcctgtgc tgactcagcc mcc 23 <210> 162 <211> 18 <212> DNA <213> Artificial <220> <223> 0L9 (HuVLIO) <400> 162 caggcagggc tgactcag 18 <210> 163 <211> 23 <212> DNA <213> Artificial <220> <223> OCL (HuCL2) <400> 163 tgaacattct gtaggggcca ctg 23 <210> 164 <211> 23 <212> DNA <213> Artificial <220> <223> OCL (HuCL7) <400> 164 agagcattct gcaggggcca ctg 23 <210> 165 <211> 23 <212> DNA <213> Artificial <220> <223> OH1(HuVH1B7A) <400> 165 cagrtgcagc tggtgcartc tgg 23 <210> 166 <211> 23 <212> DNA <213> Artificial <220> <223> OH1 (HuVHIC) <400> 166 saggtccagc tggtrcagtc tgg 23 <210> 167 <211> 23 <212> DNA <213> Artificial <220> <223> 0H2 (HuVH2B) <400> 167 cagrtcacct tgaaggagtc tgg 23 <210> 168 <211 > 18 <212> DNA <213> Artificial <220> <223> 0H3 (HuVH3A) <400> 168 gaggtgcagc tggtggag 18 <210> 169 <211> 23 <212> DNA <213> Artificial <220> <223> 0H4 (HuVH3C) <400> 169 gaggtgcagc tggtggagwc ygg 23 <210> 170 <211> 23 <212> DNA <213> Artificial <220> <223> OH5 (HuVH4B) <400> 170 caggtgcagc tacagcagtg ggg 23 <210> 171 <211> 23 <212> DNA <213> Artificial <220> <223> OH6 (HuVH4C) <400> 171 cagstgcagc tgcaggagtc sgg 23 <210> 172 <211> 23 <212> DNA <213> Artificial <220> <223> OH7 (HuVH6A) <400> 172 caggtacagc tgcagcagtc agg 23 <210> 173 <211 > 24 <212> DNA <213> Artificial <220> <223> OCM (HuCIgM) <400> 173 tggaagaggc acgttctttt cttt 24 <210> 174 <211 > 41 <212> DNA <213> Artificial <220> <223> OK1S (HuVK1 B-SAL) <400> 174 tgagcacaca ggtcgacgga catccagwtg acccagtctc c 41 <210> 175 <211 > 41 <212> DNA <213> Artificial <220> <223> OK2S (HuVK2-SAL) <400> 175 tgagcacaca ggtcgacgga tgttgtgatg actcagtctc c 41 <210> 176 <211> 41 <212> DNA <213> Artificial <220> <223> OK3S (HuVK2B2-SAL) <400> 176 tgagcacaca ggtcgacgga tattgtgatg acccagactc c 41 <210> 177 <211 > 41 <212> DNA <213> Artificial <220> <223> OK4S (HuVK3 B-SAL) <400> 177 tgagcacaca ggtcgacgga aattgtgwtg acrcagtctc c 41 <210> 178 <211 > 41 <212> DNA <213> Artificial <220> <223> 0K5S (HuVK5-SAL) <400> 178 tgagcacaca ggtcgacgga aacgacactc acgcagtctc c 41 <210> 179 <211 > 41 <212> DNA <213> Artificial <220> <223> 0K6S (HuVK6-SAL) <400> 179 tgagcacaca ggtcgacgga aattgtgctg actcagtctc c 41 <210> 180 <211> 48 <212> DNA <213> Artificial <220> <223> OJK1 (HuJK1-NOT) <400> 180 gagtcattct cgacttgcgg ccgcacgttt gatttccacc ttggtccc 48 <210> 181 <211> 48 <212> DNA <213> Artificial <220> <223> OJK2 (HuJK2-NOT) <400> 181 gagtcattct cgacttgcgg ccgcacgttt gatctccagc ttggtccc 48 <210> 182 <211> 48 <212> DNA <213> Artificial <220> <223> OJK3 (HuJK3-NOT) <400> 182 gagtcattct cgacttgcgg ccgcacgttt gatatccact ttggtccc 48 <210> 183 <211> 48 <212> DNA <213> Artificial <220> <223> OJK4 (HuJK4-NOT) <400> 183 gagtcattct cgacttgcgg ccgcacgttt gatctccacc ttggtccc 48

<210> 184 <211> 48 <212> DNA <213> Artificial <220> <223> 0JK5 (HuJK5-N0T) <400> 184 gagtcattct cgacttgcgg ccgcacgttt aatctccagt cgtgtccc 48 <210> 185 <211 > 41 <212> DNA <213> Artificial <220> <223> 0L1S (HuVL1 A-SAL) <400> 185 tgagcacaca ggtcgacgca gtctgtgctg actcagccac c 41 <210> 186 <211 > 41 <212> DNA <213> Artificial <220> <223> 0L1S (HuVL1 B-SAL) <400> 186 tgagcacaca ggtcgacgca gtctgtgytg acgcagccgc c 41 <210> 187 <211> 41 <212> DNA <213> Artificial <220> <223> 0L1S (HuVL1C-SAL) <400> 187 tgagcacaca ggtcgacgca gtctgtcgtg acgcagccgc c 41 <210> 188 <211> 38 <212> DNA <213> Artificial <220> <223> 0L2S (HuVL2B-SAL) <400> 188 tgagcacaca ggtcgacgca gtctgccctg actcagcc 38 <210> 189 <211 > 41 <212> DNA <213> Artificial <220> <223> 0L3S (HuVL3A-SAL) <400> 189 tgagcacaca ggtcgacgtc ctatgwgctg actcagccac c 41 <210> 190 <211> 41 <212> DNA <213> Artificial <220> <223> 0L4S (HuVL3B-SAL) <400>190 tgagcacaca ggtcgacgtc ttctgagctg actcaggacc c 41 <210> 191 <211> 38 <212> DNA <213> Artificial <220> <223> OL5S (HuVL4B-SAL) <400> 191 tgagcacaca ggtcgacgca gcytgtgctg actcaatc 38 <210> 192 <211 > 41 <212> DNA <213> Artificial <220> <223> OL6S (HuVL5-SAL) <400> 192 tgagcacaca ggtcgacgca ggctgtgctg actcagccgt c 41 <210> 193 <211> 41 <212> DNA <213> Artificial <220> <223> OL7S (HuVL6-SAL) <400> 193 tgagcacaca ggtcgacgaa ttttatgctg actcagcccc a 41 <210> 194 <211 > 41 <212> DNA <213> Artificial <220> <223> OL8S (HuVL7/8-SAL) <400> 194 tgagcacaca ggtcgacgca grctgtggtg acycaggagc c 41 <210> 195 <211 > 41 <212> DNA <213> Artificial <220> <223> OL9S (HuVL9-SAL) <400> 195 tgagcacaca ggtcgacgcw gcctgtgctg actcagccmc c 41 <210> 196 <211> 36 <212> DNA <213> Artificial <220> <223> 0L9S (HuVL1 O-SAL) <400> 196 tgagcacaca ggtcgacgca ggcagggctg actcag 36 <210> 197 <211> 48 <212> DNA <213> Artificial <220> <223> OJL1 (HuJL1-NOT) <400> 197 gagtcattct cgacttgcgg ccgcacctag gacggtgacc ttggtccc 48 <210> 198 <211> 48 <212> DNA <213> Artificial <220> <223> OJL2 (HuJL2/3-NOT) <400> 198 gagtcattct cgacttgcgg ccgcacctag gacggtcagc ttggtccc 48 <210> 199 <211> 48 <212> DNA <213> Artificial <220> <223> OJL3 (HuJL7-NOT) <400> 199 gagtcattct cgacttgcgg ccgcaccgag gacggtcagc tgggtgcc 48 <210> 200 <211> 56 <212> DNA <213> Artificial <220> <223> 0H1S (HuVH1 B-SFI) <400> 200 gtcctcgcaa ctgcggccca gccggccatg gcccagrtgc agctggtgca rtctgg 56 <210> 201 <211> 56 <212> DNA <213> Artificial <220> <223> 0H1S (HuVH1 C-SFI) <400> 201 gtcctcgcaa ctgcggccca gccggccatg gccsaggtcc agctggtrca gtctgg 56 <210> 202 <211> 56 <212> DNA <213> Artificial <220> <223> OH2S (HuVH2B-SFI) <400> 202 gtcctcgcaa ctgcggccca gccggccatg gcccagrtca ccttgaagga gtctgg 56 <210> 203 <211> 51 <212> DNA <213> Artificial <220> <223> OH3S (HuVH3A-SFI) <400> 203 gtcctcgcaa ctgcggccca gccggccatg gccgaggtgc agctggtgga g 51 <210> 204 <211> 56 <212> DNA <213> Artificial <220> <223> OH4S (HuVH3C-SFI) <400> 204 gtcctcgcaa ctgcggccca gccggccatg gccgaggtgc agctggtgga gwcygg 56 <210> 205 <211> 56 <212> DNA <213> Artificial <220> <223> OH5S (HuVH4B-SFI) <400> 205 gtcctcgcaa ctgcggccca gccggccatg gcccaggtgc agctacagca gtgggg 56 <210> 206 <211> 56 <212> DNA <213> Artificial <220> <223> OH6S (HuVH4C-SFI) <400> 206 gtcctcgcaa ctgcggccca gccggccatg gcccagstgc agctgcagga gtcsgg 56

<210> 207 <211> 56 <212> DNA <213> Artificial <220> <223> 0H7S (HuVH6A-SFI) <400> 207 gtcctcgcaa ctgcggccca gccggccatg gcccaggtac agctgcagca gtcagg 56 <210> 208 <211> 36 <212> DNA <213> Artificial <220> <223> OJH1 (HuJH1/2-XHO) <400> 208 gagtcattct cgactcgaga crgtgaccag ggtgcc 36 <210> 209 <211> 36 <212> DNA <213> Artificial <220> <223> OJH2 (HuJH3-XHO) <400> 209 gagtcattct cgactcgaga cggtgaccat tgtccc 36 <210 210 <211> 36 <212> DNA <213> Artificial <220 <223> OJH3 (HuJH4/5-XHO) <400 210 gagtcattct cgactcgaga cggtgaccag ggttcc 36 <210 211 <211> 36 <212> DNA <213> Artificial <220 <223> 0JH4 (HuJH6-XH0) <400> 211 gagtcattct cgactcgaga cggtgaccgt ggtccc 36 <210> 212 <211> 735 <212> DNA <213> Artificial <220> <223> SC06-141 <220 <221 > CDS <222> (1)..(735) <400> 212 gag gtc cag ctg gtg cag tct ggg get gag gtg aag aag eet ggg gce 48

Glu Val Gin Leu Val Gin Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 1-5 10 15 tea gtg aag gtc tee tgc aag get tct ggg tac acc tte acc ggc tac 96

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Gly Tyr 20 25 30 tat gtg tac tgg gtg ega cag gcc eet gga caa ggg ett gag tgg atg 144

Tyr Val Tyr Trp Val Arg Gin Ala Pro Gly Gin Gly Leu Glu Trp Met 35 40 45 gga tgg ate age get tac aat ggt aac aca aac tat gea cag aag tte 192

Gly Trp Ile Ser Ala Tyr Asn Gly Asn Thr Asn Tyr Ala Gin Lys Phe 50 55 60 cag ggc aga gtc aeg att acc gcg gac aaa tee aeg age aca gcc tac 240

Gin Gly Arg Val Thr Ile Thr Ala Asp Lys Ser Thr Ser Thr Ala Tyr 65 70 75 80 atg gag ctg age age ctg aga tct gaa gac aeg get gtg tat tac tgt 288

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 gcg aga agt aga tee ctg gac gtc tgg ggc caa ggg acc aeg gtc acc 336

Ala Arg Ser Arg Ser Leu Asp Val Trp Gly Gin Gly Thr Thr Val Thr 100 105 110 gtc teg age ggt aeg ggc ggt tea ggc gga acc ggc age ggc act ggc 384

Val Ser Ser Gly Thr Gly Gly Ser Gly Gly Thr Gly Ser Gly Thr Gly 115 120 125 ggg teg aeg gat gtt gtg atg act cag tct cca gac tee ctg get gtg 432

Gly Ser Thr Asp Val Val Met Thr Gin Ser Pro Asp Ser Leu Ala Val 130 135 140 tct ctg ggc gag agg gee acc atc aac tgc aag tee age cag agt gtt 480

Ser Leu Gly Glu Arg Ala Thr Ile Asn Cys Lys Ser Ser Gin Ser Val 145 150 155 160 tta tac age tee aac aat aag aac tac tta get tgg tac cag cag aaa 528

Leu Tyr Ser Ser Asn Asn Lys Asn Tyr Leu Ala Trp Tyr Gin Gin Lys 165 170 175 cca gga cag eet eet aag ctg etc att tac tgg gea tct acc egg gaa 576

Pro Gly Gin Pro Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg Glu 180 185 190 tee ggg gtc eet gac ega tte agt ggc age ggg tct ggg aca gat tte 624

Ser Gly Val Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe 195 200 205 act etc acc ate age age ctg cag get gaa gat gtg gea gtt tat tac 672

Thr Leu Thr Ile Ser Ser Leu Gin Ala Glu Asp Val Ala Val Tyr Tyr 210 215 220 tgt cag caa tat tat agt act eet etc act tte ggc gga ggg acc aaa 720

Cys Gin Gin Tyr Tyr Ser Thr Pro Leu Thr Phe Gly Gly Gly Thr Lys 225 230 235 240 gtg gat atc aaa egt 735

Val Asp Ile Lys Arg 245 <210> 213 <211 > 245 <212> PRT <213> Artificial <220> <223> Synthetic Construct <400 213

Glu Val Gin Leu Val Gin Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 15 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Gly Tyr 20 25 30

Tyr Val Tyr Trp Val Arg Gin Ala Pro Gly Gin Gly Leu Glu Trp Met 35 40 45

Gly Trp Ile Ser Ala Tyr Asn Gly Asn Thr Asn Tyr Ala Gin Lys Phe 50 55 60

Gin Gly Arg Val Thr Ile Thr Ala Asp Lys Ser Thr Ser Thr Ala Tyr 65 70 75 80

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95

Ala Arg Ser Arg Ser Leu Asp Val Trp Gly Gin Gly Thr Thr Val Thr 100 105 110

Val Ser Ser Gly Thr Gly Gly Ser Gly Gly Thr Gly Ser Gly Thr Gly 115 120 125

Gly Ser Thr Asp Val Val Met Thr Gin Ser Pro Asp Ser Leu Ala Val 130 135 140

Ser Leu Gly Glu Arg Ala Thr Ile Asn Cys Lys Ser Ser Gin Ser Val 145 150 155 160

Leu Tyr Ser Ser Asn Asn Lys Asn Tyr Leu Ala Trp Tyr Gin Gin Lys 165 170 175

Pro Gly Gin Pro Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg Glu 180 185 190

Ser Gly Val Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe 195 200 205

Thr Leu Thr Ile Ser Ser Leu Gin Ala Glu Asp Val Ala Val Tyr Tyr 210 215 220

Cys Gin Gin Tyr Tyr Ser Thr Pro Leu Thr Phe Gly Gly Gly Thr Lys 225 230 235 240

Val Asp Ile Lys Arg 245 <210> 214 <211> 741 <212> DNA <213> Artificial <220> <223> SC06-272 <220> <221 > CDS <222> (1)..(741) <400 214 cag atg cag ctg gtg cag tct ggg get gag gtg aag aag cct ggg tee 48

Gin Met Gin Leu Val Gin Ser Gly Ala Glu Val Lys Lys Pro Gly Ser 15 10 15 teg gtg aag gtc tee tgc aag get tet gga ggc ace ttc tee agt tat 96

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Ser Ser Tyr 20 25 30 get ate acc tgg gtg ega cag gee cct gga caa ggg ett gag tgg atg 144

Ala Ile Thr Trp Val Arg Gin Ala Pro Gly Gin Gly Leu Glu Trp Met 35 40 45 gga ggg ate ate ggt atg ttt ggt tea aca aac tac gca cag aac ttc 192

Gly Gly lie lie Gly Met Phe Gly Ser Thr Asn Tyr Ala Gin Asn Phe 50 55 60 cag ggc aga gtc aeg att acc geg gac gaa tee aeg age aca gee tac 240

Gin Gly Arg Val Thr lie Thr Ala Asp Glu Ser Thr Ser Thr Ala Tyr 65 70 75 80 atg gag ctg age age etc aga tet gag gac aeg gee gtg tat tac tgt 288

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 geg aga agt act ggt tat tac cct gca tac etc cac cac tgg ggc cag 336

Ala Arg Ser Thr Gly Tyr Tyr Pro Ala Tyr Leu His His Trp Gly Gin 100 105 110 ggc acc ctg gtc acc gtc teg age ggt aeg ggc ggt tea ggc gga acc 384

Gly Thr Leu Val Thr Val Ser Ser Gly Thr Gly Gly Ser Gly Gly Thr 115 120 125 ggc age ggc act ggc ggg teg aeg cag tet gee ctg act cag eet ege 432

Gly Ser Gly Thr Gly Gly Ser Thr Gin Ser Ala Leu Thr Gin Pro Arg 130 135 140 tea gtg tee ggg tet cct gga cag tea gtc acc ate tee tgc act gga 480

Ser Val Ser Gly Ser Pro Gly Gin Ser Val Thr lie Ser Cys Thr Gly 145 150 155 160 acc age agt gat gtt ggt ggt tat aac tat gtc tee tgg tac caa cag 528

Thr Ser Ser Asp Val Gly Gly Tyr Asn Tyr Val Ser Trp Tyr Gin Gin 165 170 175 cac cca ggc aaa gee ccc aaa etc atg att tat gat gtc agt aag egg 576

His Pro Gly Lys Ala Pro Lys Leu Met lie Tyr Asp Val Ser Lys Arg 180 185 190 ccc tea ggg gtc cct gat ege ttc tet ggc tee aag tet ggc aac aeg 624

Pro Ser Gly Val Pro Asp Arg Phe Ser Gly Ser Lys Ser Gly Asn Thr 195 200 205 gee tee ctg acc ate tet ggg etc cag get gag gat gag get gat tat 672

Ala Ser Leu Thr lie Ser Gly Leu Gin Ala Glu Asp Glu Ala Asp Tyr 210 215 220 tac tgc age tea tat aca age age age act cat gtc ttc gga act ggg 720

Tyr Cys Ser Ser Tyr Thr Ser Ser Ser Thr His Val Phe Gly Thr Gly 225 230 235 240 acc aag gtc acc gtc eta ggt 741

Thr Lys Val Thr Val Leu Gly 245 <210> 215 <211 > 247 <212> PRT <213> Artificial <220> <223> Synthetic Construct <400 215

Gin Met Gin Leu Val Gin Ser Gly Ala Glu Val Lys Lys Pro Gly Ser 15 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Ser Ser Tyr 20 25 30

Ala lie Thr Trp Val Arg Gin Ala Pro Gly Gin Gly Leu Glu Trp Met 35 40 45

Gly Gly He lie Gly Met Phe Gly Ser Thr Asn Tyr Ala Gin Asn Phe 50 55 60

Gin Gly Arg Val Thr Ile Thr Ala Asp Glu Ser Thr Ser Thr Ala Tyr 65 70 75 80

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95

Ala Arg Ser Thr Gly Tyr Tyr Pro Ala Tyr Leu His His Trp Gly Gin 100 105 110

Gly Thr Leu Val Thr Val Ser Ser Gly Thr Gly Gly Ser Gly Gly Thr 115 120 125

Gly Ser Gly Thr Gly Gly Ser Thr Gin Ser Ala Leu Thr Gin Pro Arg 130 135 140

Ser Val Ser Gly Ser Pro Gly Gin Ser Val Thr lie Ser Cys Thr Gly 145 150 155 160

Thr Ser Ser Asp Val Gly Gly Tyr Asn Tyr Val Ser Trp Tyr Gin Gin 165 170 175

His Pro Gly Lys Ala Pro Lys Leu Met Ile Tyr Asp Val Ser Lys Arg 180 185 190

Pro Ser Gly Val Pro Asp Arg Phe Ser Gly Ser Lys Ser Gly Asn Thr 195 200 205

Ala Ser Leu Thr lie Ser Gly Leu Gin Ala Glu Asp Glu Ala Asp Tyr 210 215 220

Tyr Cys Ser Ser Tyr Thr Ser Ser Ser Thr His Val Phe Gly Thr Gly 225 230 235 240

Thr Lys Val Thr Val Leu Gly 245 <210> 216 <211> 738 <212> DNA <213> Artificial <220> <223> SC06-296 <220> <221 > CDS <222> (1)..(738) <400 216 gag gtg cag ctg gtg gag acc ggg get gag gtg aag aag cct ggg gee 48

Glu Val Gin Leu Val Glu Thr Gly Ala Glu Val Lys Lys Pro Gly Ala 15 10 15 tea gtg aag gtt tee tgc aag gca tet gga tac acc ttc acc age tac 96

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr 20 25 30 tat atg cac tgg gtg ega cag gee cct gga caa ggg ett gag tgg atg 144

Tyr Met His Trp Val Arg Gin Ala Pro Gly Gin Gly Leu Glu Trp Met 35 40 45 gga tgg ate aac eet aac agt ggt ggc aca aac tat gca cag aag ttt 192

Gly Trp lie Asn Pro Asn Ser Gly Gly Thr Asn Tyr Ala Gin Lys Phe 50 55 60 cag ggc agg gtc acc atg acc agg gac aeg tee ate age aca gee tac 240

Gin Gly Arg Val Thr Met Thr Arg Asp Thr Ser lie Ser Thr Ala Tyr 65 70 75 80 atg gag ctg age agg ctg aga tet gac gac aeg gee gtg tat tac tgt 288

Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys 85 90 95 geg aga gag ggg aaa tgg gga cct caa geg get ttt gat ate tgg ggc 336

Ala Arg Glu Gly Lys Trp Gly Pro Gin Ala Ala Phe Asp lie Trp Gly 100 105 110 caa ggg aca atg gtc acc gtc teg age ggt aeg ggc ggt tea ggc gga 384

Gin Gly Thr Met Val Thr Val Ser Ser Gly Thr Gly Gly Ser Gly Gly 115 120 125 acc ggc age ggc act ggc ggg teg aeg gaa att gtg atg aeg cag tet 432

Thr Gly Ser Gly Thr Gly Gly Ser Thr Glu lie Val Met Thr Gin Ser 130 135 140 cca ggc acc ctg tet ttg tet cca ggg gaa aga gee acc etc tee tgc 480

Pro Gly Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys 145 150 155 160 agg gee agt cag agt gtt age age age tac tta gee tgg tac cag cag 528

Arg Ala Ser Gin Ser Val Ser Ser Ser Tyr Leu Ala Trp Tyr Gin Gin 165 170 175 aaa cct ggc cag get ccc agg etc etc ate tat gat gca tee age agg 576

Lys Pro Gly Gin Ala Pro Arg Leu Leu He Tyr Asp Ala Ser Ser Arg 180 185 190 gee act gac ate cca gac agg ttc agt ggc agt ggg tet ggg aca gac 624

Ala Thr Asp lie Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp 195 200 205 ttc act etc acc ate age aga ctg gag cct gaa gat ttt gca gtg tat 672

Phe Thr Leu Thr lie Ser Arg Leu Glu Pro Glu Asp Phe Ala Val Tyr 210 215 220 tac tgt cag cag tat ggt age tea ett tgg aeg ttc ggc caa ggg acc 720

Tyr Cys Gin Gin Tyr Gly Ser Ser Leu Trp Thr Phe Gly Gin Gly Thr 225 230 235 240 aag gtg gag ate aaa cgt 738

Lys Val Glu lie Lys Arg 245 <210> 217 <211 > 246 <212> PRT <213> Artificial <220> <223> Synthetic Construct <400> 217

Glu Val Gin Leu Val Glu Thr Gly Ala Glu Val Lys Lys Pro Gly Ala 15 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr 20 25 30

Tyr Met His Trp Val Arg Gin Ala Pro Gly Gin Gly Leu Glu Trp Met 35 40 45

Gly Trp Ile Asn Pro Asn Ser Gly Gly Thr Asn Tyr Ala Gin Lys Phe 50 55 60

Gin Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr 65 70 75 80

Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys 85 90 95

Ala Arg Glu Gly Lys Trp Gly Pro Gin Ala Ala Phe Asp Ile Trp Gly 100 105 110

Gin Gly Thr Met Val Thr Val Ser Ser Gly Thr Gly Gly Ser Gly Gly 115 120 125

Thr Gly Ser Gly Thr Gly Gly Ser Thr Glu Ile Val Met Thr Gin Ser 130 135 140

Pro Gly Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys 145 150 155 160

Arg Ala Ser Gin Ser Val Ser Ser Ser Tyr Leu Ala Trp Tyr Gin Gin 165 170 175

Lys Pro Gly Gin Ala Pro Arg Leu Leu Ile Tyr Asp Ala Ser Ser Arg 180 185 190

Ala Thr Asp Ile Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp 195 200 205

Phe Thr Leu Thr Ile Ser Arg Leu Glu Pro Glu Asp Phe Ala Val Tyr 210 215 220

Tyr Cys Gin Gin Tyr Gly Ser Ser Leu Trp Thr Phe Gly Gin Gly Thr 225 230 235 240

Lys Val Glu Ile Lys Arg 245 <210> 218 <211> 738 <212> DNA <213> Artificial <220> <223> SC06-301 <220> <221 > CDS <222> (1)..(738) <400 218 gag gtg cag ctg gta gag tct ggg gga ggc ttg gta cag cct ggg ggg 48

Glu Val Gin Leu Val Glu Ser Gly Gly Gly Leu Val Gin Pro Gly Gly 15 10 15 tcc ctg aga etc tcc tgt gca gcc tct gga ttc acc ttt age ate tat 96

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Ile Tyr 20 25 30 gcc atg age tgg gtc ege cag gca eea ggg aag ggg ctg gag tgg gte 144

Ala Met Ser Trp Val Arg Gin Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45 tea get att agt agt agt ggt gat age aca tac tac gca gac tcc gtg 192

Ser Ala lie Ser Ser Ser Gly Asp Ser Thr Tyr Tyr Ala Asp Ser Val 50 55 60 aag ggc egg ttc acc ate tcc aga gac aac gcc agg aac aeg ctg tat 240

Lys Gly Arg Phe Thr lie Ser Arg Asp Asn Ala Arg Asn Thr Leu Tyr 65 70 75 80 ctg caa atg aac agt ctg aga gcc gag gac aeg get gtg tat tac tgt 288

Leu Gin Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 geg aga geg tat ggc tac aeg ttc gac ccc tgg ggc cag gga acc ctg 336

Ala Arg Ala Tyr Gly Tyr Thr Phe Asp Pro Trp Gly Gin Gly Thr Leu 100 105 110 gtc acc gtc teg age ggt aeg ggc ggt tea ggc gga acc ggc age ggc 384

Val Thr Val Ser Ser Gly Thr Gly Gly Ser Gly Gly Thr Gly Ser Gly 115 120 125 act ggc ggg teg aeg gaa att gtg ctg act cag tct eea etc tcc ctg 432

Thr Gly Gly Ser Thr Glu lie Val Leu Thr Gin Ser Pro Leu Ser Leu 130 135 140 ccc gtc acc cct gga gag ccg gcc tcc ate tcc tgc agg tct agt cag 480

Pro Val Thr Pro Gly Glu Pro Ala Ser lie Ser Cys Arg Ser Ser Gin 145 150 155 160 age etc ctg cat agt aat gga tac aac tat ttg gat tgg tac ctg cag 528

Ser Leu Leu His Ser Asn Gly Tyr Asn Tyr Leu Asp Trp Tyr Leu Gin 165 170 175 aag eea ggg cag tct eea cag etc ctg ate tat ttg ggt tct aat egg 576

Lys Pro Gly Gin Ser Pro Gin Leu Leu lie Tyr Leu Gly Ser Asn Arg 180 185 190 gcc tcc ggg gtc cct gac agg ttc agt ggc agt gga tea ggc aca gat 624

Ala Ser Gly Val Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp 195 200 205 ttt aca ctg aaa ate age aga gtg gag get gag gat gtt ggg gtt tat 672

Phe Thr Leu Lys lie Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr 210 215 220 tac tgc atg caa get eta caa act ccc etc act ttc ggc gga ggg acc 720

Tyr Cys Met Gin Ala Leu Gin Thr Pro Leu Thr Phe Gly Gly Gly Thr 225 230 235 240 aag gtg gag ate aaa cgt 738

Lys Val Glu lie Lys Arg 245 <210> 219 <211 > 246 <212> PRT <213> Artificial <220> <223> Synthetic Construct <400> 219

Glu Val Gin Leu Val Glu Ser Gly Gly Gly Leu Val Gin Pro Gly Gly 15 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Ile Tyr 20 25 30

Ala Met Ser Trp Val Arg Gin Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45

Ser Ala Ile Ser Ser Ser Gly Asp Ser Thr Tyr Tyr Ala Asp Ser Val 50 55 60

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Arg Asn Thr Leu Tyr 65 70 75 80

Leu Gin Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95

Ala Arg Ala Tyr Gly Tyr Thr Phe Asp Pro Trp Gly Gin Gly Thr Leu 100 105 110

Val Thr Val Ser Ser Gly Thr Gly Gly Ser Gly Gly Thr Gly Ser Gly 115 120 125

Thr Gly Gly Ser Thr Glu Ile Val Leu Thr Gin Ser Pro Leu Ser Leu 130 135 140

Pro Val Thr Pro Gly Glu Pro Ala Ser Ile Ser Cys Arg Ser Ser Gin 145 150 155 160

Ser Leu Leu His Ser Asn Gly Tyr Asn Tyr Leu Asp Trp Tyr Leu Gin 165 170 175

Lys Pro Gly Gin Ser Pro Gin Leu Leu Ile Tyr Leu Gly Ser Asn Arg 180 185 190

Ala Ser Gly Val Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp 195 200 205

Phe Thr Leu Lys Ile Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr 210 215 220

Tyr Cys Met Gin Ala Leu Gin Thr Pro Leu Thr Phe Gly Gly Gly Thr 225 230 235 240

Lys Val Glu Ile Lys Arg 245 <210> 220 <211> 738 <212> DNA <213> Artificial <220> <223> SC06-327 <220> <221 > CDS <222> (1)..(738) <400> 220 gag gtg cag ctg gtg gag acc ggg get gag gtg aag aag cct ggg tee 48

Glu Val Gin Leu Val Glu Thr Gly Ala Glu Val Lys Lys Pro Gly Ser 15 10 15 teg gtg aag gte tee tgc aag gee tet gga ggc acc ttc agg acc cat 96

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Arg Thr His 20 25 30 get ate agt tgg gtg ega cag gee cct gga caa ggg ett gag tgg atg 144

Ala lie Ser Trp Val Arg Gin Ala Pro Gly Gin Gly Leu Glu Trp Met 35 40 45 gga ggg ate ate get ate ttc gga aca gca aac tac gca cag aag ttc 192

Gly Gly Ile Ile Ala Ile Phe Gly Thr Ala Asn Tyr Ala Gin Lys Phe 50 55 60 cag ggc aga ate aeg att acc geg gac gaa tee aeg agt aca gee tac 240

Gin Gly Arg He Thr lie Thr Ala Asp Glu Ser Thr Ser Thr Ala Tyr 65 70 75 80 atg gag ctg age age ctg aga tet gag gac aeg gee gtg tat ttc tgt 288

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Phe Cys 85 90 95 geg aga ggc agt ggt tat cat ata teg aca ccc ttt gac aac tgg ggc 336

Ala Arg Gly Ser Gly Tyr His He Ser Thr Pro Phe Asp Asn Trp Gly 100 105 110 cag gga acc ctg gte acc gte teg age ggt aeg ggc ggt tea ggc gga 384

Gin Gly Thr Leu Val Thr Val Ser Ser Gly Thr Gly Gly Ser Gly Gly 115 120 125 acc ggc age ggc act ggc ggg teg aeg tec tat gtg ctg act cag cca 432

Pro Ser Val Ser Val Ala Pro Gly Gin Thr Ala Arg He Thr Cys Gly 145 150 155 160 gga aac aac att gga agt aaa ggt gtg cac tgg tac cag cag aag cct 528

Gly Asn Asn He Gly Ser Lys Gly Val His Trp Tyr Gin Gin Lys Pro 165 170 175 ggc cag gee cct gtg ctg gte gte tat gat gat age gac egg ccc tea 576

Gly Gin Ala Pro Val Leu Val Val Tyr Asp Asp Ser Asp Arg Pro Ser 180 185 190 ggg ate cct gag ega ttc tet ggc tee aac tet ggg aac aeg gee acc 624

Gly He Pro Glu Arg Phe Ser Gly Ser Asn Ser Gly Asn Thr Ala Thr 195 200 205 ctg acc ate age agg gte gaa gee ggg gat gag gee gac tat tac tgt 672

Leu Thr lie Ser Arg Val Glu Ala Gly Asp Glu Ala Asp Tyr Tyr Cys 210 215 220 cag gtg tgg gat agt agt agt gat cat gtg gta ttc ggc gga ggg acc 720

Gin Val Trp Asp Ser Ser Ser Asp His Val Val Phe Gly Gly Gly Thr 225 230 235 240 aag ctg acc gte eta ggt 738

Lys Leu Thr Val Leu Gly 245 <210> 221 <211 > 246 <212> PRT <213> Artificial <220> <223> Synthetic Construct <400> 221

Glu Val Gin Leu Val Glu Thr Gly Ala Glu Val Lys Lys Pro Gly Ser 15 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Arg Thr His 20 25 30

Ala lie Ser Trp Val Arg Gin Ala Pro Gly Gin Gly Leu Glu Trp Met 35 40 45

Gly Gly Ile Ile Ala Ile Phe Gly Thr Ala Asn Tyr Ala Gin Lys Phe 50 55 60

Gin Gly Arg Ile Thr Ile Thr Ala Asp Glu Ser Thr Ser Thr Ala Tyr 65 70 75 80

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Phe Cys 85 90 95

Ala Arg Gly Ser Gly Tyr His Ile Ser Thr Pro Phe Asp Asn Trp Gly 100 105 110

Gin Gly Thr Leu Val Thr Val Ser Ser Gly Thr Gly Gly Ser Gly Gly 115 120 125

Thr Gly Ser Gly Thr Gly Gly Ser Thr Ser Tyr Val Leu Thr Gin Pro 130 135 140

Pro Ser Val Ser Val Ala Pro Gly Gin Thr Ala Arg Ile Thr Cys Gly 145 150 155 160

Gly Asn Asn Ile Gly Ser Lys Gly Val His Trp Tyr Gin Gin Lys Pro 165 170 175

Gly Gin Ala Pro Val Leu Val Val Tyr Asp Asp Ser Asp Arg Pro Ser 180 185 190

Gly Ile Pro Glu Arg Phe Ser Gly Ser Asn Ser Gly Asn Thr Ala Thr 195 200 205

Leu Thr Ile Ser Arg Val Glu Ala Gly Asp Glu Ala Asp Tyr Tyr Cys 210 215 220

Gin Val Trp Asp Ser Ser Ser Asp His Val Val Phe Gly Gly Gly Thr 225 230 235 240

Lys Leu Thr Val Leu Gly 245 <210> 222 <211> 756 <212> DNA <213> Artificial <220> <223> SC06-328 <220> <221 > CDS <222> (1)..(756) <400> 222 gag gtg cag ctg gtg gag tct ggg get gag gtg aag aag cct ggg tee 48

Glu Val Gin Leu Val Glu Ser Gly Ala Glu Val Lys Lys Pro Gly Ser 15 10 15 teg gtg aag gtc tee tgc aag get tct gga cac ate ttc age ggc tat 96

Ser Val Lys Val Ser Cys Lys Ala Ser Gly His Ile Phe Ser Gly Tyr 20 25 30 gca ate agt tgg gtg ega cag gee cct gga caa ggg ett gag tgg atg 144

Ala Ile Ser Trp Val Arg Gin Ala Pro Gly Gin Gly Leu Glu Trp Met 35 40 45 gga ggg ate ate cct ate ttt ggt aca aca aac tac gca cag aag ttc 192

Gly Gly lie lie Pro lie Phe Gly Thr Thr Asn Tyr Ala Gin Lys Phe 50 55 60 cag ggc aga gtc aeg att ace geg gac caa tee aeg age aca gee tac 240

Gin Gly Arg Val Thr lie Thr Ala Asp Gin Ser Thr Ser Thr Ala Tyr 65 70 75 80 atg gac ctg age aac ttg aga tct gag gac aeg gee gtc tat tac tgt 288

Met Asp Leu Ser Asn Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 geg aga gtg aaa gat gga tat tgt act ett acc age tgc cct gtc ggc 336

Ala Arg Val Lys Asp Gly Tyr Cys Thr Leu Thr Ser Cys Pro Val Gly 100 105 110 tgg tac ttc gat etc tgg ggc cgt ggc acc ctg gtc act gtc teg age 384

Trp Tyr Phe Asp Leu Trp Gly Arg Gly Thr Leu Val Thr Val Ser Ser 115 120 125 ggt aeg ggc ggt tea ggc gga acc ggc age ggc act ggc ggg teg aeg 432

Gly Thr Gly Gly Ser Gly Gly Thr Gly Ser Gly Thr Gly Gly Ser Thr 130 135 140 gaa att gtg atg aeg cag tct cca ggc acc ctg tct ttg tct cca ggg 480

Glu lie Val Met Thr Gin Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly 145 150 155 160 gaa aga gee acc etc teg tgc agg gee agt cag agt gtt age age age 528

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gin Ser Val Ser Ser Ser 165 170 175 tac tta gee tgg tac cag cag aaa cct ggc cag get ccc agg etc etc 576

Tyr Leu Ala Trp Tyr Gin Gin Lys Pro Gly Gin Ala Pro Arg Leu Leu 180 185 190 ate ttt ggt gee tee age agg gee act ggc ate cca gac agg ttc agt 624 lie Phe Gly Ala Ser Ser Arg Ala Thr Gly lie Pro Asp Arg Phe Ser 195 200 205 ggc agt ggg tct ggg aca gac ttc act etc acc ate age aga ctg gag 672

Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr lie Ser Arg Leu Glu 210 215 220 cct gaa gat ttt gca gtg tat tac tgt cag cag tat ggt age tea etc 720

Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gin Gin Tyr Gly Ser Ser Leu 225 230 235 240 act ttc ggc gga ggg acc aag ctg gag ate aaa cgt 756

Thr Phe Gly Gly Gly Thr Lys Leu Glu lie Lys Arg 245 250 <210> 223 <211 > 252 <212> PRT <213> Artificial <220> <223> Synthetic Construct <400> 223

Glu Val Gin Leu Val Glu Ser Gly Ala Glu Val Lys Lys Pro Gly Ser 15 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly His Ile Phe Ser Gly Tyr 20 25 30

Ala Ile Ser Trp Val Arg Gin Ala Pro Gly Gin Gly Leu Glu Trp Met 35 40 45

Gly Gly Ile Ile Pro Ile Phe Gly Thr Thr Asn Tyr Ala Gin Lys Phe 50 55 60

Gin Gly Arg Val Thr Ile Thr Ala Asp Gin Ser Thr Ser Thr Ala Tyr 65 70 75 80

Met Asp Leu Ser Asn Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95

Ala Arg Val Lys Asp Gly Tyr Cys Thr Leu Thr Ser Cys Pro Val Gly 100 105 110

Trp Tyr Phe Asp Leu Trp Gly Arg Gly Thr Leu Val Thr Val Ser Ser 115 120 125

Gly Thr Gly Gly Ser Gly Gly Thr Gly Ser Gly Thr Gly Gly Ser Thr 130 135 140

Glu Ile Val Met Thr Gin Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly 145 150 155 160

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gin Ser Val Ser Ser Ser 165 170 175

Tyr Leu Ala Trp Tyr Gin Gin Lys Pro Gly Gin Ala Pro Arg Leu Leu 180 185 190

Ile Phe Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser 195 200 205

Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu 210 215 220

Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gin Gin Tyr Gly Ser Ser Leu 225 230 235 240

Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys Arg 245 250 <210> 224 <211> 738 <212> DNA <213> Artificial <220> <223> SC06-329 <220> <221 > CDS <222> (1)..(738) <400> 224 gag gtc cag ctg gta cag tct ggg get gag gtt aag aag cct ggg tee 48

Glu Val Gin Leu Val Gin Ser Gly Ala Glu Val Lys Lys Pro Gly Ser 15 10 15 teg gtg aag gtc tee tgc aag get tct gga ggc ate ttc aga age aat 96

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly lie Phe Arg Ser Asn 20 25 30 tct ate agt tgg gtg ega cag gee cct ggg caa ggg ett gag tgg atg 144

Ser lie Ser Trp Val Arg Gin Ala Pro Gly Gin Gly Leu Glu Trp Met 35 40 45 gga ggg ate ttc get ett ttc gga aca aca gac tac geg cag aag ttc 192

Gly Gly lie Phe Ala Leu Phe Gly Thr Thr Asp Tyr Ala Gin Lys Phe 50 55 60 cag ggc aga gtc aeg att ace geg gac gaa tct teg acc aca gtc tac 240

Gin Gly Arg Val Thr lie Thr Ala Asp Glu Ser Ser Thr Thr Val Tyr 65 70 75 80 ctg gag ctg agt age ctg aca tct gag gac aeg gee gtt tat tac tgt 288

Leu Glu Leu Ser Ser Leu Thr Ser Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 geg aga ggc agt ggc tac acc aca ege aac tac ttt gac tac tgg ggc 336

Ala Arg Gly Ser Gly Tyr Thr Thr Arg Asn Tyr Phe Asp Tyr Trp Gly 100 105 110 cag ggc acc ctg gtc acc gtc teg age ggt aeg ggc ggt tea ggc gga 384

Gin Gly Thr Leu Val Thr Val Ser Ser Gly Thr Gly Gly Ser Gly Gly 115 120 125 acc ggc age ggc act ggc ggg teg aeg gaa att gtg ctg act cag tct 432

Thr Gly Ser Gly Thr Gly Gly Ser Thr Glu lie Val Leu Thr Gin Ser 130 135 140 cca ggc acc ctg tct ttg tct cca ggg gaa aga gee aca etc tee tgc 480

Pro Gly Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys 145 ISO 155 160 agg gee agt cag agt gtt age age aac tac tta ggc tgg tac cag cag 528

Arg Ala Ser Gin Ser Val Ser Ser Asn Tyr Leu Gly Trp Tyr Gin Gin 165 170 175 aaa cct ggc cag get ccc agg etc ctg ate tat ggt gca tee age agg 576

Lys Pro Gly Gin Ala Pro Arg Leu Leu lie Tyr Gly Ala Ser Ser Arg 180 185 190 gee agt ggc ate cca gac agg ttc agt ggc ggt ggg tct ggg aca gac 624

Ala Ser Gly lie Pro Asp Arg Phe Ser Gly Gly Gly Ser Gly Thr Asp 195 200 205 ttc act etc acc ate age aga ctg gag cct gaa gat ttt gca gtg tat 672

Phe Thr Leu Thr lie Ser Arg Leu Glu Pro Glu Asp Phe Ala Val Tyr 210 215 220 tac tgt cag cag tat ggt age tea ccc etc act ttc ggc gga ggg acc 720

Tyr Cys Gin Gin Tyr Gly Ser Ser Pro Leu Thr Phe Gly Gly Gly Thr 225 230 235 240 aag gtg gag ate aaa cgt 738

Lys Val Glu lie Lys Arg 245 <210> 225 <211 > 246 <212> PRT <213> Artificial <220> <223> Synthetic Construct <400> 225

Glu Val Gin Leu Val Gin Ser Gly Ala Glu Val Lys Lys Pro Gly Ser 1 5 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Ile Phe Arg Ser Asn 20 25 30

Ser Ile Ser Trp Val Arg Gin Ala Pro Gly Gin Gly Leu Glu Trp Met 35 40 45

Gly Gly Ile Phe Ala Leu Phe Gly Thr Thr Asp Tyr Ala Gin Lys Phe 50 55 60

Gin Gly Arg Val Thr Ile Thr Ala Asp Glu Ser Ser Thr Thr Val Tyr 65 70 75 80

Leu Glu Leu Ser Ser Leu Thr Ser Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95

Ala Arg Gly Ser Gly Tyr Thr Thr Arg Asn Tyr Phe Asp Tyr Trp Gly 100 105 110

Gin Gly Thr Leu Val Thr Val Ser Ser Gly Thr Gly Gly Ser Gly Gly 115 120 125

Thr Gly Ser Gly Thr Gly Gly Ser Thr Glu Ile Val Leu Thr Gin Ser 130 135 140

Pro Gly Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys 145 150 155 160

Arg Ala Ser Gin Ser Val Ser Ser Asn Tyr Leu Gly Trp Tyr Gin Gin 165 170 175

Lys Pro Gly Gin Ala Pro Arg Leu Leu Ile Tyr Gly Ala Ser Ser Arg 180 185 190

Ala Ser Gly Ile Pro Asp Arg Phe Ser Gly Gly Gly Ser Gly Thr Asp 195 200 205

Phe Thr Leu Thr Ile Ser Arg Leu Glu Pro Glu Asp Phe Ala Val Tyr 210 215 220

Tyr Cys Gin Gin Tyr Gly Ser Ser Pro Leu Thr Phe Gly Gly Gly Thr 225 230 235 240

Lys Val Glu Ile Lys Arg 245 <210> 226 <211> 729 <212> DNA <213> Artificial <220> <223> SC06-332 <220> <221 > CDS <222> (1)..(729) <400> 226 cag gtg cag ctg gtg cag tct ggg get gag gtg aag aag cct ggg tee 48

Gin Val Gin Leu Val Gin Ser Gly Ala Glu Val Lys Lys Pro Gly Ser 15 10 15 teg gta aag gtc tee tgc aag get tct gga ggc eee tte ege aat ttt 96

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Pro Phe Arg Asn Phe 20 25 30 get ate aac tgg gtg ega cag gee cct gga caa ggg ett gag tgg atg 144

Ala lie Asn Trp Val Arg Gin Ala Pro Gly Gin Gly Leu Glu Trp Met 35 40 45 gga ggg ate ate get gtc ttt ggg aeg aca aag tac gca cat aag ttc 192

Gly Gly Ile Ile Ala Val Phe Gly Thr Thr Lys Tyr Ala His Lys Phe 50 55 60 cag ggc aga gtc ace ate acc geg gac gac tee aca aat aca get tac 240

Gin Gly Arg Val Thr lie Thr Ala Asp Asp Ser Thr Asn Thr Ala Tyr 65 70 75 80 atg gag ctg ggc age ctg aaa tct gag gac aeg gee gtg tat tac tgt 288

Met Glu Leu Gly Ser Leu Lys Ser Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 geg aga ggt eee cac tac tac tee tee tac atg gac gtc tgg ggc gaa 336

Ala Arg Gly Pro His Tyr Tyr Ser Ser Tyr Met Asp Val Trp Gly Glu 100 105 110 ggg acc aeg gtc acc gtc teg age ggt aeg ggc ggt tea ggc gga acc 384

Gly Thr Thr Val Thr Val Ser Ser Gly Thr Gly Gly Ser Gly Gly Thr 115 120 125 ggc age ggc act ggc ggg teg aeg gac ate cag ttg acc cag tct cca 432

Gly Ser Gly Thr Gly Gly Ser Thr Asp lie Gin Leu Thr Gin Ser Pro 130 135 140 tee tee ctg tct gca tct gta gga gac aga gtc acc ate act tgc egg 480

Ser Ser Leu Ser Ala Ser Val Gly Asp Arg Val Thr lie Thr Cys Arg 145 150 155 160 geg agt cag ggc att age act tat tta gee tgg tat cag cag aaa eee 528

Ala Ser Gin Gly lie Ser Thr Tyr Leu Ala Trp Tyr Gin Gin Lys Pro 165 170 175 ggg aaa gtt cct aaa etc ctg ate tat get gca tee act ttg caa tea 576

Gly Lys Val Pro Lys Leu Leu lie Tyr Ala Ala Ser Thr Leu Gin Ser 180 185 190 ggg gtc cca tct egg ttc agt ggc agt gga tct ggg aca gat ttc act 624

Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr 195 200 205 etc acc ate age age ctg cag cct gaa gat gtt gca act tat tac tgt 672

Leu Thr lie Ser Ser Leu Gin Pro Glu Asp Val Ala Thr Tyr Tyr Cys 210 215 220 caa aag tat aac agt gee cct tct ttc ggc cct ggg acc aaa gtg gat 720

Gin Lys Tyr Asn Ser Ala Pro Ser Phe Gly Pro Gly Thr Lys Val Asp 225 230 235 240 ate aaa cgt 729 lie Lys Arg <210> 227 <211 > 243 <212> PRT <213> Artificial <220> <223> Synthetic Construct <400> 227

Gin Val Gin Leu Val Gin Ser Gly Ala Glu Val Lys Lys Pro Gly Ser IS 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Pro Phe Arg Asn Phe 20 25 30

Ala Ile Asn Trp Val Arg Gin Ala Pro Gly Gin Gly Leu Glu Trp Met 35 40 45

Gly Gly Ile Ile Ala Val Phe Gly Thr Thr Lys Tyr Ala His Lys Phe 50 55 60

Gin Gly Arg Val Thr Ile Thr Ala Asp Asp Ser Thr Asn Thr Ala Tyr 65 70 75 80

Met Glu Leu Gly Ser Leu Lys Ser Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95

Ala Arg Gly Pro His Tyr Tyr Ser Ser Tyr Met Asp Val Trp Gly Glu 100 105 110

Gly Thr Thr Val Thr Val Ser Ser Gly Thr Gly Gly Ser Gly Gly Thr 115 120 125

Gly Ser Gly Thr Gly Gly Ser Thr Asp Ile Gin Leu Thr Gin Ser Pro 130 135 140

Ser Ser Leu Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Arg 145 150 155 160

Ala Ser Gin Gly Ile Ser Thr Tyr Leu Ala Trp Tyr Gin Gin Lys Pro 165 170 175

Gly Lys Val Pro Lys Leu Leu Ile Tyr Ala Ala Ser Thr Leu Gin Ser 180 185 190

Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr 195 200 205

Leu Thr Ile Ser Ser Leu Gin Pro Glu Asp Val Ala Thr Tyr Tyr Cys 210 215 220

Gin Lys Tyr Asn Ser Ala Pro Ser Phe Gly Pro Gly Thr Lys Val Asp 225 230 235 240

Ile Lys Arg <210> 228 <211> 735 <212> DNA <213> Artificial <220> <223> SC06-334 <220> <221 > CDS <222> (1)..(735) <400> 228 gag gtg cag ctg gtg gag act ggg get gag gtg aag aag cct ggg tee 48

Glu Val Gin Leu Val Glu Thr Gly Ala Glu Val Lys Lys Pro Gly Ser 15 10 15 teg gtg aag gtc ccc tgc aaa tet tet gga age ccc tte agg agt aat 96

Ser Val Lys Val Pro Cys Lys Ser Ser Gly Ser Pro Phe Arg Ser Asn 20 25 30 get gtc age tgg gtg ega cag gee ecc gga caa ggg ett gag tgg gtg 144

Ala Val Ser Trp Val Arg Gin Ala Pro Gly Gin Gly Leu Glu Trp Val 35 40 45 gga gga ate etc ggt gtc ttt ggt tea cca age tac gca cag aag ttc 192

Gly Gly lie Leu Gly Val Phe Gly Ser Pro Ser Tyr Ala Gin Lys Phe 50 55 60 cag ggc aga gtc aeg att acc geg gac gaa tee ace aac aca gtc cae 240

Gin Gly Arg Val Thr lie Thr Ala Asp Glu Ser Thr Asn Thr Val His 65 70 75 80 atg gag ctg aga ggt ttg aga tet gag gac aeg gee gtg tat tat tgt 288

Met Glu Leu Arg Gly Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 geg aga ggt cct acc tac tac tac tee tac atg gac gtc tgg ggc aaa 336

Ala Arg Gly Pro Thr Tyr Tyr Tyr Ser Tyr Met Asp Val Trp Gly Lys 100 105 110 ggg acc aeg gtc acc gtc teg age ggt aeg ggc ggt tea ggc gga acc 384

Gly Thr Thr Val Thr Val Ser Ser Gly Thr Gly Gly Ser Gly Gly Thr 115 120 125 ggc age ggc act ggc ggg teg aeg tee tat gtg ctg act cag cca ccc 432

Gly Ser Gly Thr Gly Gly Ser Thr Ser Tyr Val Leu Thr Gin Pro Pro 130 135 140 teg gag tea gtg gee cca gga cag aeg gee agg att acc tgt ggg gga 480

Ser Glu Ser Val Ala Pro Gly Gin Thr Ala Arg lie Thr Cys Gly Gly 145 150 155 160 aat aac att gga aga aat agt gtg cae tgg tat cag cag aag cca ggc 528

Asn Asn lie Gly Arg Asn Ser Val His Trp Tyr Gin Gin Lys Pro Gly 165 170 175 cag gee cct gtg ctg gtc gtg tat gat gat age gac egg ccc tea ggg 576

Gin Ala Pro Val Leu Val Val Tyr Asp Asp Ser Asp Arg Pro Ser Gly 180 185 190 ate cct gag ega ttt tet ggc tee aag tet ggg aac aeg gee acc ctg 624 lie Pro Glu Arg Phe Ser Gly Ser Lys Ser Gly Asn Thr Ala Thr Leu 195 200 205 att ate age agg gtc gaa gtc ggg gat gag gee gac tac tac tgt cag 672 lie lie Ser Arg Val Glu Val Gly Asp Glu Ala Asp Tyr Tyr Cys Gin 210 215 220 gtg tgg cat agt agt agt gat cat tat gtc ttc gga act ggg acc aag 720

Val Trp His Ser Ser Ser Asp His Tyr Val Phe Gly Thr Gly Thr Lys 225 230 235 240 gtc acc gtc eta ggt 735

Val Thr Val Leu Gly 245 <210> 229 <211> 245 <212> PRT <213> Artificial <220> <223> Synthetic Construct <400> 229

Glu Val Gin Leu Val Glu Thr Gly Ala Glu Val Lys Lys Pro Gly Ser 15 10 15

Ser Val Lys Val Pro Cys Lys Ser Ser Gly Ser Pro Phe Arg Ser Asn 20 25 30

Ala Val Ser Trp Val Arg Gin Ala Pro Gly Gin Gly Leu Glu Trp Val 35 40 45

Gly Gly Ile Leu Gly Val Phe Gly Ser Pro Ser Tyr Ala Gin Lys Phe 50 55 60

Gin Gly Arg Val Thr Ile Thr Ala Asp Glu Ser Thr Asn Thr Val His 65 70 75 80

Met Glu Leu Arg Gly Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95

Ala Arg Gly Pro Thr Tyr Tyr Tyr Ser Tyr Met Asp Val Trp Gly Lys 100 105 110

Gly Thr Thr Val Thr Val Ser Ser Gly Thr Gly Gly Ser Gly Gly Thr 115 120 125

Gly Ser Gly Thr Gly Gly Ser Thr Ser Tyr Val Leu Thr Gin Pro Pro 130 135 140

Ser Glu Ser Val Ala Pro Gly Gin Thr Ala Arg Ile Thr Cys Gly Gly 145 150 155 160

Asn Asn Ile Gly Arg Asn Ser Val His Trp Tyr Gin Gin Lys Pro Gly 165 170 175

Gin Ala Pro Val Leu Val Val Tyr Asp Asp Ser Asp Arg Pro Ser Gly 180 185 190

Ile Pro Glu Arg Phe Ser Gly Ser Lys Ser Gly Asn Thr Ala Thr Leu 195 200 205

Ile Ile Ser Arg Val Glu Val Gly Asp Glu Ala Asp Tyr Tyr Cys Gin 210 215 220

Val Trp His Ser Ser Ser Asp His Tyr Val Phe Gly Thr Gly Thr Lys 225 230 235 240

Val Thr Val Leu Gly 245 <210> 230 <211> 735 <212> DNA <213> Artificial <220> <223> SC06-336 <220> <221 > CDS <222> (1)..(735) <400> 230 cag atg cag ctg gta caa tct gga get gag gtg aag aag cct ggg tee 48

Gin Met Gin Leu Val Gin Ser Gly Ala Glu Val Lys Lys Pro Gly Ser 15 10 15 teg gtg aag gtc tee tgc aag get tct gga ggc ace ttc age age tat 96

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Ser Ser Tyr 20 25 30 get ate age tgg gtg ega cag gee eet gga caa ggg ett gag tgg atg 144

Ala Ile Ser Trp Val Arg Gin Ala Pro Gly Gin Gly Leu Glu Trp Met 35 40 45 gga ggg ate ttc ggt atg ttt ggg aca gca aac tac geg cag aag ttc 192

Gly Gly lie Phe Gly Met Phe Gly Thr Ala Asn Tyr Ala Gin Lys Phe 50 55 60 cag ggc aga gtc aeg att acc geg gac gaa ttc aeg age geg gee tac 240

Gin Gly Arg Val Thr lie Thr Ala Asp Glu Phe Thr Ser Ala Ala Tyr 65 70 75 80 atg gag ctg age age ctg gga tct gag gac aeg gee atg tat tac tgt 288

Met Glu Leu Ser Ser Leu Gly Ser Glu Asp Thr Ala Met Tyr Tyr Cys 85 90 95 geg agg tct agt ggt tat tac ccc caa tac ttc cag gac tgg ggc cag 336

Ala Arg Ser Ser Gly Tyr Tyr Pro Gin Tyr Phe Gin Asp Trp Gly Gin 100 105 110 ggc acc ctg gtc acc gtc teg age ggt aeg ggc ggt tea ggc gga acc 384

Gly Thr Leu Val Thr Val Ser Ser Gly Thr Gly Gly Ser Gly Gly Thr 115 120 125 ggc age ggc act ggc ggg teg aeg gaa att gtg atg aca cag tct cca 432

Gly Ser Gly Thr Gly Gly Ser Thr Glu lie Val Met Thr Gin Ser Pro 130 135 140 ggc acc ctg tct ttg tct cca ggg caa aga gee acc etc tee tgc agg 480

Gly Thr Leu Ser Leu Ser Pro Gly Gin Arg Ala Thr Leu Ser Cys Arg 145 150 155 160 gee agt cag agt gtt age age age tac tta gee tgg tac cag cag aaa 528

Ala Ser Gin Ser Val Ser Ser Ser Tyr Leu Ala Trp Tyr Gin Gin Lys 165 170 175 cct ggc cag get ccc aga etc etc atg tat ggt gca tee age agg gee 576

Pro Gly Gin Ala Pro Arg Leu Leu Met Tyr Gly Ala Ser Ser Arg Ala 180 185 190 act ggc ate cca gac agg ttc agt ggc agt ggg tct ggg aca gac ttc 624

Thr Leu Thr lie Ser Arg Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr 210 215 220 tgt cag cag tat ggt age tea teg etc act ttc ggc gga ggg acc aag 720

Cys Gin Gin Tyr Gly Ser Ser Ser Leu Thr Phe Gly Gly Gly Thr Lys 225 230 235 240 ctg gag ate aaa cgt 735

Leu Glu lie Lys Arg 245 <210> 231 <211 > 245 <212> PRT <213> Artificial <220> <223> Synthetic Construct <400> 231

Gin Met Gin Leu Val Gin Ser Gly Ala Glu Val Lys Lys Pro Gly Ser 15 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Ser Ser Tyr 20 25 30

Ala Ile Ser Trp Val Arg Gin Ala Pro Gly Gin Gly Leu Glu Trp Met 35 40 45

Gly Gly lie Phe Gly Met Phe Gly Thr Ala Asn Tyr Ala Gin Lys Phe 50 55 60

Gin Gly Arg Val Thr lie Thr Ala Asp Glu Phe Thr Ser Ala Ala Tyr 65 70 75 80

Met Glu Leu Ser Ser Leu Gly Ser Glu Asp Thr Ala Met Tyr Tyr Cys 85 90 95

Ala Arg Ser Ser Gly Tyr Tyr Pro Gin Tyr Phe Gin Asp Trp Gly Gin 100 105 HO

Gly Thr Leu Val Thr Val Ser Ser Gly Thr Gly Gly Ser Gly Gly Thr 115 120 125

Gly Ser Gly Thr Gly Gly Ser Thr Glu lie Val Met Thr Gin Ser Pro 130 135 140

Gly Thr Leu Ser Leu Ser Pro Gly Gin Arg Ala Thr Leu Ser Cys Arg 145 150 155 160

Ala Ser Gin Ser Val Ser Ser Ser Tyr Leu Ala Trp Tyr Gin Gin Lys 165 170 175

Pro Gly Gin Ala Pro Arg Leu Leu Met Tyr Gly Ala Ser Ser Arg Ala 180 185 190

Thr Gly lie Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe 195 200 205

Thr Leu Thr lie Ser Arg Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr 210 215 220

Cys Gin Gin Tyr Gly Ser Ser Ser Leu Thr Phe Gly Gly Gly Thr Lys 225 230 235 240

Leu Glu lie Lys Arg 245 <210> 232 <211> 738 <212> DNA <213> Artificial <220> <223> SC06-339 <220> <221 > CDS <222> (1)..(738) <400> 232 gag gtg cag ctg gtg gag tcc ggg get gag gtg aag aag cct ggg tcc 48

Glu Val Gin Leu Val Glu Ser Gly Ala Glu Val Lys Lys Pro Gly Ser 15 10 15 teg gtg aag gtc tcc tgc aag get tet gga ggc ate ttc aac agt tat 96

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly lie Phe Asn Ser Tyr 20 25 30 get ate age tgg gtg ega cag gee cct gga caa ggg ett gag tgg atg 144

Ala lie Ser Trp Val Arg Gin Ala Pro Gly Gin Gly Leu Glu Trp Met 35 40 45 gga ggc ate ate get ate ttt cat aca cca aag tac gea cag aag tte 192

Gly Gly Ile Ile Ala Ile Phe His Thr Pro Lys Tyr Ala Gin Lys Phe 50 55 60 cag ggc aga gtc aeg att ace geg gac gaa tee aeg aac aca gcc tae 240

Gin Gly Arg Val Thr Ile Thr Ala Asp Glu Ser Thr Asn Thr Ala Tyr 65 70 75 80 atg gaa ctg aga age ctg aaa tet gag gae aeg gcc ctg tat tac tgt 288

Met Glu Leu Arg Ser Leu Lys Ser Glu Asp Thr Åla Leu Tyr Tyr Cys 85 90 95 geg aga ggg tee act tac gat ttt teg agt ggc ett gac tac tgg ggc 336

Ala Arg Gly Ser Thr Tyr Asp Phe Ser Ser Gly Leu Asp Tyr Trp Gly 100 105 110 cag gga acc ctg gtc acc gtc teg age ggt aeg ggc ggt tea ggc gga 384

Gin Gly Thr Leu Val Thr Val Ser Ser Gly Thr Gly Gly Ser Gly Gly 115 120 125 acc ggc age ggc act ggc ggg teg aeg cag gea ggg ctg act cag cca 432

Thr Gly Ser Gly Thr Gly Gly Ser Thr Gin Ala Gly Leu Thr Gin Pro 130 135 140 ccc teg gtg tea gtg gcc cca gga cag aeg gcc agg att acc tgt ggg 480

Pro Ser Val Ser Val Ala Pro Gly Gin Thr Ala Arg Ile Thr Cys Gly 145 150 155 160 gga aac aac att gga agt aaa agt gtg cac tgg tac cag cag aag cca 528

Gly Asn Asn Ile Gly Ser Lys Ser Val His Trp Tyr Gin Gin Lys Pro 165 170 175 ggc cag gcc eet gtc eta gtc gtc tat gat gat age gac egg ccc tea 576

Gly Gin Ala Pro Val Leu Val Val Tyr Asp Asp Ser Asp Arg Pro Ser 180 185 190 ggg atc eet gag ega tte tet ggc tee aac tet ggg aac aeg gcc acc 624

Gly Ile Pro Glu Arg Phe Ser Gly Ser Asn Ser Gly Asn Thr Ala Thr 195 200 205 ctg acc atc age agg gtc gaa gcc ggg gat gag gcc gac tat tac tgt 672

Leu Thr Ile Ser Arg Val Glu Ala Gly Asp Glu Ala Asp Tyr Tyr Cys 210 215 220 cag gtg tgg gat agt agt agt gat cat gtg gta tte ggc gga ggg acc 720

Gin Val Trp Asp Ser Ser Ser Asp His Val Val Phe Gly Gly Gly Thr 225 230 235 240 aag ctg acc gtc eta ggt 738

Lys Leu Thr Val Leu Gly 245 <210> 233 <211 > 246 <212> PRT <213> Artificial <220> <223> Synthetic Construct <400> 233

Glu Val Gin Leu Val Glu Ser Gly Ala Glu Val Lys Lys Pro Gly Ser 15 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Ile Phe Asn Ser Tyr 20 25 30

Ala Ile Ser Trp Val Arg Gin Ala Pro Gly Gin Gly Leu Glu Trp Met 35 40 45

Gly Gly Ile Ile Ala Ile Phe His Thr Pro Lys Tyr Ala Gin Lys Phe 50 55 €0

Gin Gly Arg Val Thr Ile Thr Ala Asp Glu Ser Thr Asn Thr Ala Tyr 65 70 75 80

Met Glu Leu Arg Ser Leu Lys Ser Glu Asp Thr Ala Leu Tyr Tyr Cys 85 90 95

Ala Arg Gly Ser Thr Tyr Asp Phe Ser Ser Gly Leu Asp Tyr Trp Gly 100 105 110

Gin Gly Thr Leu Val Thr Val Ser Ser Gly Thr Gly Gly Ser Gly Gly 115 120 125

Thr Gly Ser Gly Thr Gly Gly Ser Thr Gin Ala Gly Leu Thr Gin Pro 130 135 140

Pro Ser Val Ser Val Ala Pro Gly Gin Thr Ala Arg Ile Thr Cys Gly 145 150 155 160

Gly Asn Asn Ile Gly Ser Lys Ser Val His Trp Tyr Gin Gin Lys Pro 165 170 175

Gly Gin Ala Pro Val Leu Val Val Tyr Asp Asp Ser Asp Arg Pro Ser 180 185 190

Gly Ile Pro Glu Arg Phe Ser Gly Ser Asn Ser Gly Asn Thr Ala Thr 195 200 205

Leu Thr Ile Ser Arg Val Glu Ala Gly Asp Glu Ala Asp Tyr Tyr Cys 210 215 220

Gin Val Trp Asp Ser Ser Ser Asp His Val Val Phe Gly Gly Gly Thr 225 230 235 240

Lys Leu Thr Val Leu Gly 245 <210> 234 <211> 768 <212> DNA <213> Artificial <220> <223> SC06-342 <220> <221 > CDS <222> (1)..(768) <400> 234 cag gtc cag ctg gtg cag tct ggg get gag gtg aag aag cct ggg tee 48

Gin Val Gin Leu Val Gin Ser Gly Ala Glu Val Lys Lys Pro Gly Ser 15 10 15 teg gtg aag gtc tee tgc aag get tct gga ggc ttc ttc age age tat 96

Ser Val Lys Val Ser Cys lys Ala Ser Gly Gly Phe Phe Ser Ser Tyr 20 25 30 get ate age tgg gtg ege eag gee eet gga caa gga ett gag tgg atg 144

Ala Ile Ser Trp Val Arg Gin Ala Pro Gly Gin Gly Leu Glu Trp Met 35 40 45 ggg ggg gtc ate cct ate ttt cgt aca gca aac tac gca cag aac ttc 192

Gly Gly Val lie Pro lie Phe Arg Thr Ala Asn Tyr Ala Gin Asn Phe 50 55 60 cag ggc aga gtc acc att acc geg gac gaa ttc aca teg tat atg gag 240

Gin Gly Arg Val Thr lie Thr Ala Asp Glu Phe Thr Ser Tyr Met Glu 65 70 75 80 ctg age age ctg aga tct gac gac aeg gee gtg tat tac tgt geg agg 288

Leu Ser Ser Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys Ala Arg 85 90 95 ttg aat tac cat gat teg ggg act tat tat aac gee ccc egg ggc tgg 336

Leu Asn Tyr His Asp Ser Gly Thr Tyr Tyr Asn Ala Pro Arg Gly Trp 100 105 110 ttc gac ccc tgg ggc cag gga acc ctg gtc acc gtc teg age ggt aeg 384

Phe Asp Pro Trp Gly Gin Gly Thr Leu Val Thr Val Ser Ser Gly Thr 115 120 125 ggc ggt tea ggc gga acc ggc age ggc act ggc ggg teg aeg gac ate 432

Gly Gly Ser Gly Gly Thr Gly Ser Gly Thr Gly Gly Ser Thr Asp lie 130 135 140 cag atg acc cag tct cca gac tee ctg get gtg tct ctg ggc gag aag 480

Gin Met Thr Gin Ser Pro Asp Ser Leu Ala Val Ser Leu Gly Glu Lys 145 150 155 160 gee acc ate aac tgc aag tee age cag agt att tta aac age tee aac 528

Ala Thr lie Asn Cys Lys Ser Ser Gin Ser lie Leu Asn Ser Ser Asn 165 170 175 aat aag aac tac tta get tgg tac cag cag aaa cca gga cag cct cct 576

Asn Lys Asn Tyr Leu Ala Trp Tyr Gin Gin Lys Pro Gly Gin Pro Pro 180 185 190 aag ctg etc att tac tgg gca tct acc egg gaa tee ggg gtc cct gac 624

Lys Leu Leu lie Tyr Trp Ala Ser Thr Arg Glu Ser Gly Val Pro Asp 195 200 205 ega ttc agt ggc age ggg tct ggg aca gat ttc act etc acc ate age 672

Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr lie Ser 210 215 220 age ctg cag get gaa gat gtg gca gtt tat tac tgt cag caa tat tat 720

Ser Leu Gin Ala Glu Asp Val Ala Val Tyr Tyr Cys Gin Gin Tyr Tyr 225 230 235 240 agt agt ccg ccg aeg ttc ggc caa ggg acc aag gtg gaa ate aaa cgt 768

Ser Ser Pro Pro Thr Phe Gly Gin Gly Thr Lys Val Glu lie Lys Arg 245 250 255 <210> 235 <211 > 256 <212> PRT <213> Artificial <220> <223> Synthetic Construct <400> 235

Gin Val Gin Leu Val Gin Ser Gly Ala Glu Val Lys Lys Pro Gly Ser 15 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Phe Phe Ser Ser Tyr 20 25 30

Ala Ile Ser Trp Val Arg Gin Ala Pro Gly Gin Gly Leu Glu Trp Met 35 40 45

Gly Gly Val lie Pro Ile Phe Arg Thr Ala Asn Tyr Ala Gin Asn Phe 50 55 60

Gin Gly Arg Val Thr lie Thr Ala Asp Glu Phe Thr Ser Tyr Met Glu 65 70 75 80

Leu Ser Ser Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys Ala Arg 85 90 95

Leu Asn Tyr His Asp Ser Gly Thr Tyr Tyr Asn Ala Pro Arg Gly Trp 100 105 110

Phe Asp Pro Trp Gly Gin Gly Thr Leu Val Thr Val Ser Ser Gly Thr 115 120 125

Gly Gly Ser Gly Gly Thr Gly Ser Gly Thr Gly Gly Ser Thr Asp lie 130 135 140

Gin Met Thr Gin Ser Pro Asp Ser Leu Ala Val Ser Leu Gly Glu Lys 145 150 155 160

Ala Thr He Asn Cys Lys Ser Ser Gin Ser lie Leu Asn Ser Ser Asn 165 170 175

Asn Lys Asn Tyr Leu Ala Trp Tyr Gin Gin Lys Pro Gly Gin Pro Pro 180 185 190

Lys Leu Leu He Tyr Trp Ala Ser Thr Arg Glu Ser Gly Val Pro Asp 195 200 205

Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr He Ser 210 215 220

Ser Leu Gin Ala Glu Asp Val Ala Val Tyr Tyr Cys Gin Gin Tyr Tyr 225 230 235 240

Ser Ser Pro Pro Thr Phe Gly Gin Gly Thr Lys Val Glu He Lys Arg 245 250 255 <210> 236 <211> 735 <212> DNA <213> Artificial <220> <223> SC06-343 <220> <221 > CDS <222> (1)..(735) <400> 236 cag gtc cag ctg gtg cag tct gga get gag gtg aag aag cct ggg tee 48

Gin Val Gin Leu Val Gin Ser Gly Ala Glu Val Lys Lys Pro Gly Ser 15 10 15 teg gtg aag gtc tee tgc aag get tct gga gtc ace tte agt tac tat 96

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Val Thr Phe Ser Tyr Tyr 20 25 30 get atg age tgg gtg ega cag gee cet gga eaa ggg ett gag tgg atg 144

Ala Met Ser Trp Val Arg Gin Ala Pro Gly Gin Gly Leu Glu Trp Met 35 40 45 gga gga ate age cct atg ttt ggg aca aca ace tac gca cag aag ttc 192

Gly Gly lie Ser Pro Met Phe Gly Thr Thr Thr Tyr Ala Gin Lys Phe 50 55 60 cag ggc aga gtc aeg att act geg gac gac tee aeg agt aca gee tac 240

Gin Gly Arg Val Thr lie Thr Ala Asp Asp Ser Thr Ser Thr Ala Tyr 65 70 75 80 atg gag gtg agg age ctg aga tct gag gac aeg gee gtg tat tac tgt 288

Met Glu Val Arg Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 geg aga tct teg aat tac tat gat agt gta tat gac tac tgg ggc cag 336

Ala Arg Ser Ser Asn Tyr Tyr Asp Ser Val Tyr Asp Tyr Trp Gly Gin 100 105 110 gga aec ctg gtc acc gtc teg age ggt aeg ggc ggt tea ggc gga acc 384

Gly Thr Leu Val Thr Val Ser Ser Gly Thr Gly Gly Ser Gly Gly Thr 115 120 125 ggc age ggc act ggc ggg teg aeg cag tct gtc gtg aeg cag ccg ccc 432

Gly Ser Gly Thr Gly Gly Ser Thr Gin Ser Val Val Thr Gin Pro Pro 130 135 140 teg gag tea gtg gee cca gga cag aeg gee agg att acc tgt ggg gga 480

Ser Glu Ser Val Ala Pro Gly Gin Thr Ala Arg lie Thr Cys Gly Gly 145 150 155 160 cat aac att gga agt aat agt gtg cac tgg tac cag cag aag eca ggc 528

His Asn lie Gly Ser Asn Ser Val His Trp Tyr Gin Gin Lys Pro Gly 165 170 175 cag gee cct gtg ctg gtc gtg tat gat aat age gac egg ccc tea ggg 576

Gin Ala Pro Val Leu Val Val Tyr Asp Asn Ser Asp Arg Pro Ser Gly 180 185 190 ate cct gag ega ttc tct ggc tee aac tct ggg aac aeg gee acc ctg 624 lie Pro Glu Arg Phe Ser Gly Ser Asn Ser Gly Asn Thr Ala Thr Leu 195 200 205 acc ate age agg gtc gaa gee ggg gat gag gee gac tat tac tgt cag 672

Thr lie Ser Arg Val Glu Ala Gly Asp Glu Ala Asp Tyr Tyr Cys Gin 210 215 220 gtg tgg ggt agt agt agt gac cat tat gtc ttc gga act ggg acc aag 720

Val Trp Gly Ser Ser Ser Asp His Tyr Val Phe Gly Thr Gly Thr Lys 225 230 235 240 gtc acc gtc eta ggt 735

Val Thr Val Leu Gly 245 <210> 237 <211 > 245 <212> PRT <213> Artificial <220> <223> Synthetic Construct <400> 237

Gin Val Gin Leu Val Gin Ser Gly Ala Glu Val Lys Lys Pro Gly Ser 15 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Val Thr Phe Ser Tyr Tyr 20 25 30

Ala Met Ser Trp Val Arg Gin Ala Pro Gly Gin Gly Leu Glu Trp Met 35 40 45

Gly Gly lie Ser Pro Met Phe Gly Thr Thr Thr Tyr Ala Gin Lys Phe 50 55 60

Gin Gly Arg Val Thr lie Thr Ala Asp Asp Ser Thr Ser Thr Ala Tyr 65 70 75 80

Met Glu Val Arg Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95

Ala Arg Ser Ser Asn Tyr Tyr Asp Ser Val Tyr Asp Tyr Trp Gly Gin 100 105 110

Gly Thr Leu Val Thr Val Ser Ser Gly Thr Gly Gly Ser Gly Gly Thr 115 120 125

Gly Ser Gly Thr Gly Gly Ser Thr Gin Ser Val Val Thr Gin Pro Pro 130 135 140

Ser Glu Ser Val Ala Pro Gly Gin Thr Ala Arg lie Thr Cys Gly Gly 145 150 155 160

His Asn lie Gly Ser Asn Ser Val His Trp Tyr Gin Gin Lys Pro Gly 165 170 175

Gin Ala Pro Val Leu Val Val Tyr Asp Asn Ser Asp Arg Pro Ser Gly 180 185 190 lie Pro Glu Arg Phe Ser Gly Ser Asn Ser Gly Asn Thr Ala Thr Leu 195 200 205

Thr lie Ser Arg Val Glu Ala Gly Asp Glu Ala Asp Tyr Tyr Cys Gin 210 215 220

Val Trp Gly Ser Ser Ser Asp His Tyr Val Phe Gly Thr Gly Thr Lys 225 230 235 240

Val Thr Val Leu Gly 245 <210> 238 <211 > 5

<212> PRT <213> Homo sapiens <400> 238

Gly Tyr Tyr Val Tyr 1 5 <210> 239 <211> 17

<212> PRT <213> Homo sapiens <400> 239

Trp lie Ser Ala Tyr Asn Gly Asn Thr Asn Tyr Ala Gin Lys Phe Gin 15 10 15

Gly <210> 240 <211 > 6

<212> PRT <213> Homo sapiens <400> 240

Ser Arg Ser Leu Asp Val 1 5 <210> 241 <211> 17 <212> PRT <213> Homo sapiens <400> 241

Lys Ser Ser Gin Ser Val Leu Tyr Ser Ser Asn Asn Lys Asn Tyr Leu 15 10 15

Ala <210> 242 <211 > 7

<212> PRT <213> Homo sapiens <400> 242

Trp Ala Ser Thr Arg Glu Ser 1 5 <210> 243 <211 > 9

<212> PRT <213> Homo sapiens <400> 243

Gin Gin Tyr Tyr Ser Thr Pro Leu Thr 1 5 <210> 244 <211 > 5

<212> PRT <213> Homo sapiens <400> 244

Ser Tyr Ala Ile Thr 1 5 <210> 245 <211> 17

<212> PRT <213> Homo sapiens <400> 245

Gly Ile Ile Gly Met Phe Gly Ser Thr Asn Tyr Ala Gin Asn Phe Gin 15 10 15

Gly <210> 246 <211 > 11

<212> PRT <213> Homo sapiens <400> 246

Ser Thr Gly Tyr Tyr Pro Ala Tyr Leu His His 15 10 <210> 247 <211 > 14

<212> PRT <213> Homo sapiens <400> 247

Thr Gly Thr Ser Ser Asp Val Gly Gly Tyr Asn Tyr Val Ser 15 10 <210> 248 <211 > 7

<212> PRT <213> Homo sapiens <400> 248

Asp Val Ser Lys Arg Pro Ser 1 5 <210> 249 <211> 10

<212> PRT <213> Homo sapiens <400> 249

Ser Ser Tyr Thr Ser Ser Ser Thr His Val 15 10 <210> 250 <211 > 5

<212> PRT <213> Homo sapiens <400> 250

Ser Tyr Tyr Met His 1 5 <210> 251 <211> 17

<212> PRT <213> Homo sapiens <400> 251

Trp Ile Asn Pro Asn Ser Gly Gly Thr Asn Tyr Ala Gin Lys Phe Gin 15 10 15

Gly <210> 252 <211 > 12

<212> PRT <213> Homo sapiens <400> 252

Glu Gly Lys Trp Gly Pro Gin Ala Ala Phe Asp Ile 15 10 <210> 253 <211 > 12

<212> PRT <213> Homo sapiens <400> 253

Arg Ala Ser Gin Ser Val Ser Ser Ser Tyr Leu Ala 1 5 10 <210> 254 <211 > 7

<212> PRT <213> Homo sapiens <400> 254

Asp Ala Ser Ser Arg Ala Thr 1 5 <210> 255 <211 > 8

<212> PRT <213> Homo sapiens <400> 255

Gin Gin Tyr Gly Ser Ser Leu Trp 1 5 <210> 256 <211 > 5

<212> PRT <213> Homo sapiens <400> 256

Ile Tyr Ala Met Ser 1 5 <210> 257 <211> 17

<212> PRT <213> Homo sapiens <400> 257

Ala Ile Ser Ser Ser Gly Asp Ser Thr Tyr Tyr Ala Asp Ser Val Lys 15 10 15

Gly <210> 258 <211 > 8

<212> PRT <213> Homo sapiens <400> 258

Ala Tyr Gly Tyr Thr Phe Asp Pro 1 5 <210> 259 <211> 16

<212> PRT <213> Homo sapiens <400> 259

Arg Ser Ser Gin Ser Leu Leu His Ser Asn Gly Tyr Asn Tyr Leu Asp 15 10 15 <210> 260 <211 > 7

<212> PRT <213> Homo sapiens <400> 260

Leu Gly Ser Asn Arg Ala Ser 1 5 <210> 261 <211 > 8

<212> PRT <213> Homo sapiens <400> 261

Met Gin Ala Leu Gin Thr Pro Leu 1 5 <210> 262 <211 > 5

<212> PRT <213> Homo sapiens <400> 262

Thr His Ala Ile Ser 1 5 <210> 263 <211> 17

<212> PRT <213> Homo sapiens <400> 263

Gly Ile Ile Ala Ile Phe Gly Thr Ala Asn Tyr Ala Gin Lys Phe Gin 15 10 15

Gly <210> 264 <211 > 12

<212> PRT <213> Homo sapiens <400> 264

Gly Ser Gly Tyr His Ile Ser Thr Pro Phe Asp Asn 15 10 <210> 265 <211 > 11

<212> PRT <213> Homo sapiens <400> 265

Gly Gly Asn Asn Ile Gly Ser Lys Gly Val His 15 10 <210> 266 <211 > 7

<212> PRT <213> Homo sapiens <400> 266

Asp Asp Ser Asp Arg Pro Ser 1 5 <210> 267 <211 > 11

<212> PRT <213> Homo sapiens <400> 267

Gin Val Trp Asp Ser Ser Ser Asp His Val Val 15 10 <210> 268 <211 > 5

<212> PRT <213> Homo sapiens <400> 268

Gly Tyr Ala Ile Ser 1 5 <210> 269 <211> 17

<212> PRT <213> Homo sapiens <400> 269

Gly Ile Ile Fro Ile Fhe Gly Thr Thr Asn Tyr Ala Gin Lys Fhe Gin 15 10 15

Gly <210> 270 <211> 19

<212> PRT <213> Homo sapiens <400> 270

Val Lys Asp Gly Tyr Cys Thr Leu Thr Ser Cys Pro Val Gly Trp Tyr 15 10 15

Phe Asp Leu <210> 271 <211 > 12

<212> PRT <213> Homo sapiens <400> 271

Arg Ala Ser Gin Ser Val Ser Ser Ser Tyr Leu Ala 15 10 <210> 272 <211 > 7

<212> PRT <213> Homo sapiens <400> 272

Gly Ala Ser Ser Arg Ala Thr 1 5 <210> 273 <211 > 8

<212> PRT <213> Homo sapiens <400> 273

Gin Gin Tyr Gly Ser Ser Leu Thr 1 5 <210> 274 <211 > 5

<212> PRT <213> Homo sapiens <400> 274

Ser Asn Ser Ile Ser 1 5 <210> 275 <211> 17

<212> PRT <213> Homo sapiens <400> 275

Gly Ile Phe Ala Leu Phe Gly Thr Thr Asp Tyr Ala Gin Lys Phe Gin 15 10 15

Gly <210> 276 <211 > 12

<212> PRT <213> Homo sapiens <400> 276

Gly Ser Gly Tyr Thr Thr Arg Asn Tyr Phe Asp Tyr 15 10 <210> 277 <211 > 12

<212> PRT <213> Homo sapiens <400> 277

Arg Ala Ser Gin Ser Val Ser Ser Asn Tyr Leu Gly 1 5 10 <210> 278 <211 > 7

<212> PRT <213> Homo sapiens <400> 278

Gly Ala Ser Ser Arg Ala Ser 1 5 <210> 279 <211 > 9

<212> PRT <213> Homo sapiens <400> 279

Gin Gin Tyr Gly Ser Ser Pro Leu Thr 1 5 <210> 280 <211 > 5

<212> PRT <213> Homo sapiens <400> 280

Asn Phe Ala Ile Asn 1 5 <210> 281 <211> 17

<212> PRT <213> Homo sapiens <400> 281

Gly Ile Ile Ala Val Phe Gly Thr Thr Lys Tyr Ala His Lys Phe Gin 15 10 15

Gly <210> 282 <211 > 11

<212> PRT <213> Homo sapiens <400> 282

Gly Pro His Tyr Tyr Ser Ser Tyr Met Asp Val 15 10 <210> 283 <211 > 11

<212> PRT <213> Homo sapiens <400> 283

Arg Ala Ser Gin Gly Ile Ser Thr Tyr Leu Ala 15 10 <210> 284 <211 > 7

<212> PRT <213> Homo sapiens <400> 284

Ala Ala Ser Thr Leu Gin Ser 1 5 <210> 285 <211 > 8

<212> PRT <213> Homo sapiens <400> 285

Gin Lys Tyr Asn Ser Ala Pro Ser 1 5 <210> 286 <211 > 5

<212> PRT <213> Homo sapiens <400> 286

Ser Asn Ala Val Ser 1 5 <210> 287 <211> 17

<212> PRT <213> Homo sapiens <400> 287

Gly Ile Leu Gly Val Phe Gly Ser Pro Ser Tyr Ala Gin Lys Phe Gin 15 10 15

Gly <210> 288 <211 > 11

<212> PRT <213> Homo sapiens <400> 288

Gly Pro Thr Tyr Tyr Tyr Ser Tyr Met Asp Val 15 10 <210> 289 <211 > 11

<212> PRT <213> Homo sapiens <400> 289

Gly Gly Asn Asn Ile Gly Arg Asn Ser Val His 15 10 <210> 290 <211 > 7

<212> PRT <213> Homo sapiens <400> 290

Asp Asp Ser Asp Arg Fro Ser 1 5 <210> 291 <211 > 11

<212> PRT <213> Homo sapiens <400> 291

Gin Val Trp His Ser Ser Ser Asp His Tyr Val 15 10 <210> 292 <211 > 5

<212> PRT <213> Homo sapiens <400> 292

Ser Tyr Ala Ile Ser 1 5 <210> 293 <211> 17

<212> PRT <213> Homo sapiens <400> 293

Gly Ile Phe Gly Met Phe Gly Thr Ala Asn Tyr Ala Gin Lys Phe Gin 15 10 15

Gly <210> 294 <211 > 11

<212> PRT <213> Homo sapiens <400> 294

Ser Ser Gly Tyr Tyr Pro Gin Tyr Phe Gin Asp 1 5 10 <210> 295 <211 > 12

<212> PRT <213> Homo sapiens <400> 295

Arg Ala Ser Gin Ser Val Ser Ser Ser Tyr Leu Ala 15 10 <210> 296 <211 > 7

<212> PRT <213> Homo sapiens <400> 296

Gly Ala Ser Ser Arg Ala Thr 1 5 <210> 297 <211 > 9

<212> PRT <213> Homo sapiens <400> 297

Gin Gin Tyr Gly Ser Ser Ser Leu Thr 1 5 <210> 298 <211 > 5

<212> PRT <213> Homo sapiens <400> 298

Ser Tyr Ala Ile Ser 1 5 <210> 299 <211> 17

<212> PRT <213> Homo sapiens <400> 299

Gly Ile Ile Ala Ile Phe His Thr Pro Lys Tyr Ala Gin Lys Phe Gin 15 10 15

Gly <210> 300 <211 > 12

<212> PRT <213> Homo sapiens <400> 300

Gly Ser Thr Tyr Asp Phe Ser Ser Gly Leu Asp Tyr 15 10 <210> 301 <211 > 11

<212> PRT <213> Homo sapiens <400> 301

Gly Gly Asn Asn ile Gly Ser Lys Ser Val His 15 10 <210> 302 <211 > 7

<212> PRT <213> Homo sapiens <400> 302

Asp Asp Ser Asp Arg Pro Ser 1 5 <210> 303 <211 > 11

<212> PRT <213> Homo sapiens <400> 303

Gin Val Trp Asp Ser Ser Ser Asp His Val Val 15 10 <210> 304 <211 > 5

<212> PRT <213> Homo sapiens <400> 304

Ser Tyr Ala Ile Ser 1 5 <210> 305 <211> 17

<212> PRT <213> Homo sapiens <400> 305

Gly Val Ile Pro Ile Phe Arg Thr Ala Asn Tyr Ala Gin Asn Phe Gin 15 10 15

Gly <210> 306 <211> 19

<212> PRT <213> Homo sapiens <400> 306

Leu Asn Tyr His Asp Ser Gly Thr Tyr Tyr Asn Ala Pro Arg Gly Trp 15 10 15

Phe Asp Pro <210> 307 <211> 17

<212> PRT <213> Homo sapiens <400> 307

Lys Ser Ser Gin Ser Ile Leu Asn Ser Ser Asn Asn Lys Asn Tyr Leu 15 10 15

Ala <210> 308 <211 > 7

<212> PRT <213> Homo sapiens <400> 308

Trp Ala Ser Thr Arg Glu Ser 1 5 <210> 309 <211 > 9

<212> PRT <213> Homo sapiens <400> 309

Gin Gin Tyr Tyr Ser Ser Pro Pro Thr 1 5 <210>310 <211 > 5

<212> PRT <213> Homo sapiens <400 310

Tyr Tyr Ala Met Ser 1 5 <210311 <211> 17

<212> PRT <213> Homo sapiens <400 311

Gly Ile Ser Pro Met Phe Gly Thr Thr Thr Tyr Ala Gin Lys Phe Gin 15 10 15

Gly <21 0> 312 <211 > 11

<212> PRT <213> Homo sapiens <400 312

Ser Ser Asn Tyr Tyr Asp Ser Val Tyr Asp Tyr 15 10 <210> 313 <211> 11

<212> PRT <213> Homo sapiens <400> 313

Gly Gly His Asn Ile Gly Ser Asn Ser Val His 15 10 <210> 314 <211> 7

<212> PRT <213> Homo sapiens <400> 314

Asp Asn Ser Asp Arg Pro Ser 1 5 <210> 315 <211> 11

<212> PRT <213> Homo sapiens <400> 315

Gin Val Trp Gly Ser Ser Ser Asp His Tyr Val 15 10 <210> 316 <211 > 1335 <212> DNA <213> Artificial <220> <223> CR6141 Heavy chain <220> <221 > CDS <222> (1)..(1335) <400> 316 gag gtc cag ctg gtg cag tct ggg get gag gtg aag aag cct ggg gee 48

Glu Val Gin Leu Val Gin Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 15 10 15 tea gtg aag gtc tee tgc aag get tct ggg tae ace ttc acc ggc tac 96

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Gly Tyr 20 25 30 tat gtg tac tgg gtg ega cag gee cct gga caa ggg ett gag tgg atg 144

Tyr Val Tyr Trp Val Arg Gin Ala Pro Gly Gin Gly Leu Glu Trp Met 35 40 45 gga tgg ate age get tac aat ggt aac aca aac tat gca cag aag ttc 192

Gly Trp Ile Ser Ala Tyr Asn Gly Asn Thr Asn Tyr Ala Gin Lys Phe 50 55 60 cag ggc aga gtc aeg att acc geg gac aaa tee aeg age aca gee tac 240

Gin Gly Arg Val Thr lie Thr Ala Asp Lys Ser Thr Ser Thr Ala Tyr 65 70 75 80 atg gag ctg age age ctg aga tct gaa gac aeg get gtg tat tac tgt 288

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 geg aga agt aga tee ctg gac gtc tgg ggc caa ggg acc aeg gtc acc 336

Ala Arg Ser Arg Ser Leu Asp Val Trp Gly Gin Gly Thr Thr Val Thr 100 105 110 gtc teg agt get age acc aag ggc ccc age gtg ttc ccc ctg gee ccc 384

Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro 115 120 125 age age aag age acc age ggc ggc aca gee gee ctg ggc tgc ctg gtg 432

Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val 130 135 140 aag gac tac ttc ccc gag ccc gtg acc gtg age tgg aac age ggc gee 480

Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala 145 150 155 160 ttg acc age ggc gtg cac acc ttc ccc gee gtg ctg cag age age ggc 528

Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gin Ser Ser Gly 165 170 175 ctg tac age ctg age age gtg gtg acc gtg ccc age age age ctg ggc 576

Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly 180 185 190 acc cag acc tac ate tgc aac gtg aac cac aag ccc age aac acc aag 624

Thr Gin Thr Tyr lie Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys 195 200 205 gtg gac aaa ege gtg gag ccc aag age tgc gac aag acc cac acc tgc 672

Val Asp Lys Arg Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys 210 215 220 ccc ccc tgc cct gcc ccc gag ctg ctg ggc gga ccc tcc gtg ttc ctg 720

Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu 225 230 235 240 ttc ccc ccc aag ccc aag gac acc ctc atg atc age egg aec ccc gag 768

Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu 245 250 255 gtg acc tgc gtg gtg gtg gac gtg age cac gag gac ccc gag gtg aag 816

Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys 260 265 270 ttc aac tgg tac gtg gac ggc gtg gag gtg cac aac gcc aag acc aag 864

Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys 275 280 285 ccc egg gag gag cag tac aac age acc tac egg gtg gtg age gtg etc 912

Pro Arg Glu Glu Gin Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu 290 295 300 acc gtg ctg cac cag gac tgg ctg aac ggc aag gag tac aag tgc aag 960

Thr Val Leu His Gin Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys 305 310 315 320 gtg age aac aag gcc ctg cct gcc ccc atc gag aag acc atc age aag 1008

Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys 325 330 335 gcc aag ggc cag ccc egg gag ccc cag gtg tac acc ctg ccc ccc age 1056

Ala Lys Gly Gin Pro Arg Glu Pro Gin Val Tyr Thr Leu Pro Pro Ser 340 345 350 egg gag gag atg acc aag aac cag gtg tee etc acc tgt ctg gtg aag 1104

Arg Glu Glu Met Thr Lys Asn Gin Val Ser Leu Thr Cys Leu Val Lys 355 360 365 ggc ttc tac ccc age gac atc gcc gtg gag tgg gag age aac ggc cag 1152

Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gin 370 375 380 ccc gag aac aac tac aag acc acc ccc cct gtg ctg gac age gac ggc 1200

Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly 385 390 395 400 age ttc ttc ctg tac age aag etc acc gtg gac aag age egg tgg cag 1248

Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gin 405 410 415 cag ggc aac gtg ttc age tgc age gtg atg cac gag gcc ctg cac aac 1296

Gin Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn 420 425 430 cac tac acc cag aag age ctg age ctg age ccc ggc aag 1335

His Tyr Thr Gin Lys Ser Leu Ser Leu Ser Pro Gly Lys 435 440 445 <210> 317 <211 >445 <212> PRT <213> Artificial <220> <223> Synthetic Construct <400> 317

Glu Val Gin Leu Val Gin Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 15 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Gly Tyr 20 25 30

Tyr Val Tyr Trp Val Arg Gin Ala Pro Gly Gin Gly Leu Glu Trp Met 35 40 45

Gly Trp Ile Ser Ala Tyr Asn Gly Asn Thr Asn Tyr Ala Gin Lys Phe 50 55 60

Gin Gly Arg Val Thr Ile Thr Ala Asp Lys Ser Thr Ser Thr Ala Tyr 65 70 75 80

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95

Ala Arg Ser Arg Ser Leu Asp Val Trp Gly Gin Gly Thr Thr Val Thr 100 105 110

Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro 115 120 125

Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val 130 135 140

Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala 145 150 155 160

Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gin Ser Ser Gly 165 170 175

Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly 180 185 190

Thr Gin Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys 195 200 205

Val Asp Lys Arg Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys 210 215 220

Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu 225 230 235 240 *

Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu 245 250 255

Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys 260 265 270

Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys 275 280 285

Pro Arg Glu Glu Gin Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu 290 295 300

Thr Val Leu His Gin Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys 305 310 315 320

Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys 325 330 335

Ala Lys Gly Gin Pro Arg Glu Pro Gin Val Tyr Thr Leu Pro Pro Ser 340 345 350

Arg Glu Glu Met Thr Lys Asn Gin Val Ser Leu Thr Cys Leu Val Lys 355 360 365

Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gin 370 375 380

Pro Glu Asn A$n Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly 385 390 395 400

Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gin 405 410 415

Gin Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn 420 425 430

His Tyr Thr Gin Lys Ser Leu Ser Leu Ser Pro Gly Lys 435 440 445 <210> 318 <211 > 657 <212> DNA <213> Artificial <220> <223> CR6141 Light chain <220> <221 > CDS <222> (1)..(657) <400 318 gat gtt gtg atg act cag tct cca gac tcc ctg get gtg tet ctg ggc 48

Asp Val Val Met Thr Gin Ser Pro Asp Ser Leu Ala Val Ser Leu Gly 15 10 15 gag agg gcc acc ate aac tgc aag tee age cag agt gtt tta tac age 96

Glu Arg Ala Thr Ile Asn Cys Lys Ser Ser Gin Ser Val Leu Tyr Ser 20 25 30 tee aac aat aag aac tac tta get tgg tac cag cag aaa eca gga cag 144

Ser Asn Asn Lys Asn Tyr Leu Ala Trp Tyr Gin Gin Lys Pro Gly Gin 35 40 45 eet cct aag ctg etc att tac tgg gca tet acc egg gaa tee ggg gtc 192

Pro Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg Glu Ser Gly Val 50 55 60 cct gac ega ttc agt ggc age ggg tet ggg aca gat ttc act etc acc 240

Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr 65 70 75 80 ate age age ctg cag get gaa gat gtg gca gtt tat tac tgt cag caa 288 lie Ser Ser Leu Gin Ala Glu Asp Val Ala Val Tyr Tyr Cys Gin Gin 85 90 95 tat tat agt act cct etc act ttc ggc gga ggg acc aaa gtg gat ate 336

Tyr Tyr Ser Thr Pro Leu Thr Phe Gly Gly Gly Thr Lys Val Asp lie 100 105 110 aaa cgt geg gcc gca ccc age gtg ttc ate ttc ccc ccc tee gac gag 384

Lys Arg Ala Ala Ala Pro Ser Val Phe lie Phe Pro Pro Ser Asp Glu 115 120 125 cag ctg aag age ggc acc gcc age gtg gtg tgc ctg ctg aac aac ttc 432

Gin Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe 130 135 140 tac ccc egg gag gcc aag gtg cag tgg aag gtg gac aac gcc ctg cag 480

Tyr Pro Arg Glu Ala Lys Val Gin Trp Lys Val Asp Asn Ala Leu Gin 145 150 155 160 age ggc aac age cag gag age gtg acc gag cag gac age aag gac tee 528

Ser Gly Asn Ser Gin Glu Ser Val Thr Glu Gin Asp Ser Lys Asp Ser 165 170 175 acc tac age ctg age age acc etc acc ctg age aag gcc gac tac gag 576

Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu 180 185 190 aag cac aag gtg tac gcc tgc gag gtg acc cac cag ggc ctg age age 624

Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gin Gly Leu Ser Ser 195 200 205 ccc gtg acc aag age ttc aac egg ggc gag tgt 657

Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 210 215 <210> 319 <211> 219 <212> PRT <213> Artificial <220> <223> Synthetic Construct <400> 319

Asp Val Val Met Thr Gin Ser Pro Asp Ser Leu Ala Val Ser Leu Gly 15 10 15

Glu Arg Ala Thr Ile Asn Cys Lys Ser Ser Gin Ser Val Leu Tyr Ser 20 25 30

Ser Asn Asn Lys Asn Tyr Leu Ala Trp Tyr Gin Gin Lys Pro Gly Gin 35 40 45

Pro Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg Glu Ser Gly Val 50 55 60

Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr 65 70 75 80

Ile Ser Ser Leu Gin Ala Glu Asp Val Ala Val Tyr Tyr Cys Gin Gin 85 90 95

Tyr Tyr Ser Thr Pro Leu Thr Phe Gly Gly Gly Thr Lys Val Asp Ile 100 105 110

Lys Arg Ala Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu 115 120 125

Gin Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe 130 135 140

Tyr Pro Arg Glu Ala Lys Val Gin Trp Lys Val Asp Asn Ala Leu Gin 145 150 155 160

Ser Gly Asn Ser Gin Glu Ser Val Thr Glu Gin Asp Ser Lys Asp Ser 165 170 175

Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu 180 185 190

Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gin Gly Leu Ser Ser 195 200 205

Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 210 215 <210> 320 <211 > 1350 <212> DNA <213> Artificial <220> <223> CR6272 Heavy chain <220> <221 > CDS <222> (1)..(1350) <400> 320 cag atg cag ctg gtg cag tct ggg get gag gtg aag aag cct ggg tee 48

Gin Met Gin Leu Val Gin Ser Gly Ala Glu Val Lys Lys Pro Gly Ser 15 10 15 teg gtg aag gtc tee tgc aag get tct gga ggc ace ttc tee agt tat 96

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Ser Ser Tyr 20 25 30 get ate ace tgg gtg ega cag gee cct gga eaa ggg ett gag tgg atg 144

Gly Gly lie lie Gly Met Phe Gly Ser Thr Asn Tyr Ala Gin Asn Phe 50 55 60 cag ggc aga gtc aeg att ace geg gac gaa tee aeg age aca gee tac 240

Gin Gly Arg Val Thr lie Thr Ala Asp Glu Ser Thr Ser Thr Ala Tyr 65 70 75 80 atg gag ctg age age etc aga tct gag gac aeg gee gtg tat tac tgt 288

Ala Arg Ser Thr Gly Tyr Tyr Pro Ala Tyr Leu His His Trp Gly Gin 100 105 110 ggc acc ctg gtc acc gtc teg agt get age acc aag ggc ccc age gtg 384

Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser Cys Asp 210 215 220 aag acc cac acc tgc ccc ccc tgc cct gee ccc gag ctg ctg ggc gga 720

Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp 370 375 380 gag age aac ggc cag ccc gag aac aac tac aag acc acc ccc eet gtg 1200

Gly Lys 450 <210> 321 <211 >450 <212> PRT <213> Artificial <220> <223> Synthetic Construct <400> 321

Gin Met Gin Leu Val Gin Ser Gly Ala Glu Val Lys Lys Pro Gly Ser 15 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Ser Ser Tyr 20 25 30

Ala Ile Thr Trp Val Arg Gin Ala Pro Gly Gin Gly Leu Glu Trp Met 35 40 45

Gly Gly lie lie Gly Met Phe Gly Ser Thr Asn Tyr Ala Gin Asn Phe 50 55 60

Gin Gly Arg Val Thr lie Thr Ala Asp Glu Ser Thr Ser Thr Ala Tyr 65 70 75 80

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95

Ala Arg Ser Thr Gly Tyr Tyr Pro Ala Tyr Leu His His Trp Gly Gin 100 105 110

Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val 115 120 125

Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala 130 135 140

Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser 145 150 155 160

Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val 165 170 175

Leu Gin Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro 180 185 190

Ser Ser Ser Leu Gly Thr Gin Thr Tyr lie Cys Asn Val Asn His Lys 195 200 205

Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser Cys Asp 210 215 220

Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly 225 230 235 240

Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met lie 245 250 255

Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu 260 265 270

Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His 275 280 285

Asn Ala Lys Thr Lys Pro Arg Glu Glu Gin Tyr Asn Ser Thr Tyr Arg 290 295 300

Val Val Ser Val Leu Thr Val Leu His Gin Asp Trp Leu Asn Gly Lys 305 310 315 320

Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu 325 330 335

Lys Thr Ile Ser Lys Ala Lys Gly Gin Pro Arg Glu Pro Gin Val Tyr 340 345 350

Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gin Val Ser Leu 355 360 365

Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp 370 375 380

Glu Ser Asn Gly Gin Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val 385 390 395 400

Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp 405 410 415

Lys Ser Arg Trp Gin Gin Gly Asn Val Phe Ser Cys Ser Val Met His 420 425 430

Glu Ala Leu His Asn His Tyr Thr Gin Lys Ser Leu Ser Leu Ser Pro 435 440 445

Gly Lys 450 <210> 322 <211 > 660 <212> DNA <213> Artificial <220> <223> CR6272 Light chain <220> <221 > CDS <222> (1)..(660) <400> 322 cag tct gcc ctg act cag cct cgc tea gtg tec ggg tet cct gga cag 48

Gin Ser Ala Leu Thr Gin Pro Arg Ser Val Ser Gly Ser Pro Gly Gin 15 10 15 tea gtc ace ate tee tgc act gga ace age agt gat gtt ggt ggt tat 96

Ser Val Thr Ile Ser Cys Thr Gly Thr Ser Ser Asp Val Gly Gly Tyr 20 25 30 aae tat gtc tee tgg tac caa cag cac cea ggc aaa gee ece aaa etc 144

Asn Tyr Val Ser Trp Tyr Gin Gin His Pro Gly Lys Ala Pro Lys Leu 35 40 45 atg att tat gat gtc agt aag egg ccc tea ggg gtc cct gat cgc ttc 192

Met Ile Tyr Asp Val Ser Lys Arg Pro Ser Gly Val Pro Asp Arg Phe 50 55 60 tct ggc tee aag tct ggc aae aeg gcc tee ctg acc ate tct ggg etc 240

Ser Gly Ser Lys Ser Gly Asn Thr Ala Ser Leu Thr lie Ser Gly Leu 65 70 75 80 cag get gag gat gag get gat tat tac tgc age tea tat aca age age 288

Gin Ala Glu Asp Glu Ala Asp Tyr Tyr Cys Ser Ser Tyr Thr Ser Ser 85 90 95 age act cat gtc ttc gga act ggg acc aag gtc acc gtc eta ggt geg 336

Ser Thr His Val Phe Gly Thr Gly Thr Lys Val Thr Val Leu Gly Ala 100 105 110 gcc gca ggc cag ccc aag gcc get ccc age gtg acc ctg ttc ccc ccc 384

Ala Ala Gly Gin Pro Lys Ala Ala Pro Ser Val Thr Leu Phe Pro Pro 115 120 125 tee tee gag gag ctg cag gcc aae aag gcc acc ctg gtg tgc etc ate 432

Ser Pro Val Lys Ala Gly Val Glu Thr Thr Thr Pro Ser Lys Gin Ser 165 170 175 aae aae aag tac gcc gcc age age tac ctg age etc acc ccc gag cag 576

Thr Val Glu Lys Thr Val Ala Pro Thr Glu Cys Ser 210 215 220 <210> 323 <211 > 220 <212> PRT <213> Artificial <220> <223> Synthetic Construct <400> 323

Gin Ser Ala Leu Thr Gin Pro Arg Ser Val Ser Gly Ser Pro Gly Gin 15 10 15

Ser Val Thr Ile Ser Cys Thr Gly Thr Ser Ser Asp Val Gly Gly Tyr 20 25 30

Asn Tyr Val Ser Trp Tyr Gin Gin His Pro Gly Lys Ala Pro Lys Leu 35 40 45

Met Ile Tyr Asp Val Ser Lys Arg Pro Ser Gly Val Pro Asp Arg Phe 50 55 €0

Ser Gly Ser Lys Ser Gly Asn Thr Ala Ser Leu Thr lie Ser Gly Leu 65 70 75 80

Gin Ala Glu Asp Glu Ala Asp Tyr Tyr Cys Ser Ser Tyr Thr Ser Ser 85 90 95

Ser Thr His Val Phe Gly Thr Gly Thr Lys Val Thr Val Leu Gly Ala 100 105 110

Ala Ala Gly Gin Pro Lys Ala Ala Pro Ser Val Thr Leu Phe Pro Pro 115 120 125

Ser Ser Glu Glu Leu Gin Ala Asn Lys Ala Thr Leu Val Cys Leu He 130 135 140

Ser Asp Phe Tyr Pro Gly Ala Val Thr Val Ala Trp Lys Ala Asp Ser 145 150 155 160

Ser Pro Val Lys Ala Gly Val Glu Thr Thr Thr Pro Ser Lys Gin Ser 165 170 175

Asn Asn Lys Tyr Ala Ala Ser Ser Tyr Leu Ser Leu Thr Pro Glu Gin 180 185 190

Trp Lys Ser His Arg Ser Tyr Ser Cys Gin Val Thr His Glu Gly Ser 195 200 205

Thr Val Glu Lys Thr Val Ala Pro Thr Glu Cys Ser 210 215 220 <210> 324 <211> 1353 <212> DNA <213> Artificial <220> <223> CR6296 Heavy chain <220> <221 > CDS <222> (1)..(1353) <400> 324 gag gtg cag ctg gtg gag acc ggg get gag gtg aag aag cct ggg gee 48

Glu Val Gin Leu Val Glu Thr Gly Ala Glu Val Lys Lys Pro Gly Ala 15 10 15 tea gtg aag gtt tec tge aag gca tet gga tac acc ttc acc age tac 96

Ala Arg Glu Gly Lys Trp Gly Pro Gin Ala Ala Phe Asp lie Trp Gly 100 105 110 caa ggg aca atg gtc acc gtc teg agt get age acc aag ggc ccc age 384

Gin Gly Thr Met Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser 115 120 125 gtg ttc ccc ctg gee ccc age age aag age acc age ggc ggc aca gee 432

Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala 130 135 140 gee ctg ggc tge ctg gtg aag gac tac ttc ccc gag ccc gtg acc gtg 480

Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val 145 150 155 160 age tgg aac age ggc gee ttg acc age ggc gtg cac acc ttc ccc gee 528

Val Leu Gin Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val 180 185 190 ccc age age age ctg ggc acc cag acc tac ate tge aac gtg aac cac 624

Pro Ser Ser Ser Leu Gly Thr Gin Thr Tyr lie Cys Asn Val Asn His 195 200 205 aag ccc age aac acc aag gtg gac aaa ege gtg gag ccc aag age tge 672

Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly 225 230 235 240 gga ccc tcc gtg ttc ctg ttc ccc ccc aag ccc aag gac acc etc atg 768

Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met 245 250 255 ate age egg acc ccc gag gtg ace tgc gtg gtg gtg gac gtg age cac 816

Arg Val Val Ser Val Leu Thr Val Leu His Gin Asp Trp Leu Asn Gly 305 310 315 320 aag gag tac aag tgc aag gtg age aac aag gcc ctg cct gcc ccc ate 1008

Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro lie 325 330 335 gag aag acc ate age aag gcc aag ggc cag ccc egg gag ccc cag gtg 1056

Glu Lys Thr lie Ser Lys Ala Lys Gly Gin Pro Arg Glu Pro Gin Val 340 345 350 tac acc ctg ccc ccc age egg gag gag atg acc aag aac cag gtg tec 1104

Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gin Val Ser 355 360 365 etc acc tgt ctg gtg aag ggc ttc tac ccc age gac ate gcc gtg gag 1152

Pro Gly Lys 450 <210> 325 <211 > 451 <212> PRT <213> Artificial <220> <223> Synthetic Construct <400> 325

Glu Val Gin Leu Val Glu Thr Gly Ala Glu Val Lys Lys Pro Gly Ala 15 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr 20 25 30

Tyr Met His Trp Val Arg Gin Ala Pro Gly Gin Gly Leu Glu Trp Met 35 40 45

Gly Trp Ile Asn Pro Asn Ser Gly Gly Thr Asn Tyr Ala Gin Lys Phe 50 55 60

Gin Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr 65 70 75 80

Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys 85 90 95

Ala Arg Glu Gly Lys Trp Gly Pro Gin Ala Ala Phe Asp Ile Trp Gly 100 105 110

Gin Gly Thr Met Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser 115 120 125

Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala 130 135 140

Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val 145 150 155 160

Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala 165 170 175

Val Leu Gin Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val 180 185 190

Pro Ser Ser Ser Leu Gly Thr Gin Thr Tyr Ile Cys Asn Val Asn His 195 200 205

Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser Cys 210 215 220

Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly 225 230 235 240

Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met 245 250 255

Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His 260 265 270

Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val 275 280 285

His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gin Tyr Asn Ser Thr Tyr 290 295 300

Arg Val Val Ser Val Leu Thr Val Leu His Gin Asp Trp Leu Asn Gly 305 310 315 320

Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile 325 330 335

Glu Lys Thr Ile Ser Lys Ala Lys Gly Gin Pro Arg Glu Pro Gin Val 340 345 350

Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gin Val Ser 355 360 365

Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu 370 375 380

Trp Glu Ser Asn Gly Gin Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro 385 390 395 400

Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val 405 410 415

Asp Lys Ser Arg Trp Gin Gin Gly Asn Val Phe Ser Cys Ser Val Met 420 425 430

His Glu Ala Leu His Asn His Tyr Thr Gin Lys Ser Leu Ser Leu Ser 435 440 445

Pro Gly Lys 450 <210> 326 <211 > 642 <212> DNA <213> Artificial <220> <223> CR6296 Light chain <220> <221 > CDS <222> (1)..(642) <400> 326 gaa att gtg atg acg cag tct cca ggc acc ctg tct ttg tct cca ggg 48

Glu Ile Val Met Thr Gin Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly 15 10 15 gaa aga gcc acc ctc tcc tgc agg gcc agt cag agt gtt age age age 96

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gin Ser Val Ser Ser Ser 20 25 30 tac tta gcc tgg tae cag cag aaa cct ggc cag get ccc agg ctc ctc 144

Tyr Leu Ala Trp Tyr Gin Gin Lys Pro Gly Gin Ala Pro Arg Leu Leu 35 40 45 ate tat gat gea tcc age agg gcc act gac atc cca gac agg ttc agt 192

Ile Tyr Asp Ala Ser Ser Arg Ala Thr Asp Ile Pro Asp Arg Phe Ser 50 55 60 ggc agt ggg tct ggg aca gac ttc act etc acc atc age aga ctg gag 240

Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu 65 70 75 80 cct gaa gat ttt gea gtg tat tac tgt cag cag tat ggt age tea ett 288

Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gin Gin Tyr Gly Ser Ser Leu 85 90 95 tgg acg ttc ggc caa ggg acc aag gtg gag atc aaa egt gcg gcc gea 336

Trp Thr Phe Gly Gin Gly Thr Lys Val Glu Ile Lys Arg Ala Ala Ala 100 105 110 ccc age gtg ttc atc ttc ccc ccc tcc gac gag cag ctg aag age ggc 384

Glu Ser Val Thr Glu Gin Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser 165 170 175 age acc ctc acc ctg age aag gcc gac tac gag aag cae aag gtg tac 576

Phe Asn Arg Gly Glu Cys 210 <210> 327 <211 > 214 <212> PRT <213> Artificial <220> <223> Synthetic Construct <400> 327

Glu Ile Val Met Thr Gin Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly 15 10 15

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gin Ser Val Ser Ser Ser 20 25 30

Tyr Leu Ala Trp Tyr Gin Gin Lys Pro Gly Gin Ala Pro Arg Leu Leu 35 40 45

Ile Tyr Asp Ala Ser Ser Arg Ala Thr Asp Ile Pro Asp Arg Phe Ser 50 55 60

Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu 65 70 75 80

Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gin Gin Tyr Gly Ser Ser Leu 85 90 95

Trp Thr Phe Gly Gin Gly Thr Lys Val Glu Ile Lys Arg Ala Ala Ala 100 105 110

Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gin Leu Lys Ser Gly 115 120 125

Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala 130 135 140

Lys Val Gin Trp Lys Val Asp Asn Ala Leu Gin Ser Gly Asn Ser Gin 145 150 155 160

Glu Ser Val Thr Glu Gin Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser 165 170 175

Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr 180 185 190

Ala Cys Glu Val Thr His Gin Gly Leu Ser Ser Pro Val Thr Lys Ser 195 200 205

Phe Asn Arg Gly Glu Cys 210 <210> 328 <211 > 1341 <212> DNA <213> Artificial <220> <223> CR6301 Heavy chain <220> <221 > CDS <222> (1)..(1341) <400> 328 gag gtg cag ctg gta gag tct ggg gga ggc ttg gta cag cct ggg ggg 48

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Ile Tyr 20 25 30 gcc atg age tgg gtc ege cag gca cca ggg aag ggg ctg gag tgg gtc 144

Ala Met Ser Trp Val Arg Gin Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45 tea get att agt agt agt ggt gat age aca tac tac gea gac tee gtg 192

Ala Arg Ala Tyr Gly Tyr Thr Phe Asp Pro Trp Gly Gin Gly Thr Leu 100 105 110 gtc acc gtc teg agt get age acc aag ggc ccc age gtg ttc ccc ctg 384

Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu 115 120 125 gcc ccc age age aag age acc age ggc ggc aca gcc gcc ctg ggc tgc 432

Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys 130 135 140 ctg gtg aag gac tac ttc ccc gag ccc gtg acc gtg age tgg aac age 480

Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser 145 150 155 160 ggc gcc ttg acc age ggc gtg cac acc ttc ccc gcc gtg ctg cag age 528

Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gin Ser 165 170 175 age ggc ctg tac age ctg age age gtg gtg acc gtg ccc age age age 576

Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser 180 185 190 ctg ggc acc cag acc tac ate tgc aac gtg aac cac aag ccc age aac 624

Leu Gly Thr Gin Thr Tyr lie Cys Asn Val Asn His Lys Pro Ser Asn 195 200 205 acc aag gtg gac aaa cgc gtg gag ccc aag age tgc gac aag acc cac 672

Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser Cys Asp Lys Thr His 210 215 220 acc tgc ccc ccc tgc eet gcc ccc gag ctg ctg ggc gga ccc tee gtg 720

Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val 225 230 235 240 tte ctg tte ccc ccc aag ccc aag gac acc etc atg ate age egg acc 768

Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr 245 250 255 ccc gag gtg acc tgc gtg gtg gtg gac gtg age cac gag gac ccc gag 816

Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu 260 265 270 gtg aag tte aac tgg tac gtg gac ggc gtg gag gtg cac aac gcc aag 864

Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys 275 280 285 acc aag ccc egg gag gag cag tac aac age acc tac egg gtg gtg age 912

Thr Lys Pro Arg Glu Glu Gin Tyr Asn Ser Thr Tyr Arg Val Val Ser 290 295 300 gtg etc acc gtg ctg cac cag gac tgg ctg aac ggc aag gag tac aag 960

Val Leu Thr Val Leu His Gin Asp Trp Leu Asn Gly Lys Glu Tyr Lys 305 310 315 320 tgc aag gtg age aac aag gcc ctg eet gee ccc ate gag aag acc atc 1008

Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile 325 330 335 age aag gcc aag ggc cag ccc egg gag ccc cag gtg tac acc ctg ccc 1056

Ser Lys Ala Lys Gly Gin Pro Arg Glu Pro Gin Val Tyr Thr Leu Pro 340 345 350 ccc age egg gag gag atg acc aag aac cag gtg tee etc acc tgt ctg 1104

Pro Ser Arg Glu Glu Met Thr Lys Asn Gin Val Ser Leu Thr Cys Leu 355 360 365 gtg aag ggc tte tac ccc age gac atc gcc gtg gag tgg gag age aac 1152

Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn 370 375 380 ggc cag ccc gag aac aac tac aag acc acc ccc eet gtg ctg gac age 1200

Gly Gin Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser 385 390 395 400 gac ggc age tte tte ctg tac age aag etc acc gtg gac aag age egg 1248

Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg 405 410 415 tgg cag cag ggc aac gtg tte age tgc age gtg atg cac gag gcc ctg 1296

Trp Gin Gin Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu 420 425 430 cac aac cac tac acc cag aag age ctg age ctg age ccc ggc aag 1341

His Asn His Tyr Thr Gin Lys Ser Leu Ser Leu Ser Pro Gly Lys 435 440 445 <210> 329 <211 >447 <212> PRT <213> Artificial <220> <223> Synthetic Construct <400> 329

Glu Val Gin Leu Val Glu Ser Gly Gly Gly Leu Val Gin Pro Gly Gly 15 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Ile Tyr 20 25 30

Ala Met Ser Trp Val Arg Gin Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45

Ser Ala Ile Ser Ser Ser Gly Asp Ser Thr Tyr Tyr Ala Asp Ser Val 50 55 €0

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Arg Asn Thr Leu Tyr 65 70 75 80

Leu Gin Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95

Ala Arg Ala Tyr Gly Tyr Thr Phe Asp Pro Trp Gly Gin Gly Thr Leu 100 105 110

Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu 115 120 125

Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys 130 135 140

Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser 145 150 155 160

Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gin Ser 165 170 175

Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser 180 185 190

Leu Gly Thr Gin Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn 195 200 205

Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser Cys Asp Lys Thr His 210 215 220

Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val 225 230 235 240

Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr 245 250 255

Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu 260 265 270

Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys 275 280 285

Thr Lys Pro Arg Glu Glu Gin Tyr Asn Ser Thr Tyr Arg Val Val Ser 290 295 300

Val Leu Thr Val Leu His Gin Asp Trp Leu Asn Gly Lys Glu Tyr Lys 305 310 315 320

Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro lie Glu Lys Thr lie 325 330 335

Ser Lys Ala Lys Gly Gin Pro Arg Glu Pro Gin Val Tyr Thr Leu Pro 340 345 350

Pro Ser Arg Glu Glu Met Thr Lys Asn Gin Val Ser Leu Thr Cys Leu 355 360 365

Val Lys Gly Phe Tyr Pro Ser Asp lie Ala Val Glu Trp Glu Ser Asn 370 375 380

Gly Gin Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser 385 390 395 400

Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg 405 410 415

Trp Gin Gin Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu 420 425 430

His Asn His Tyr Thr Gin Lys Ser Leu Ser Leu Ser Pro Gly Lys 435 440 445 <210> 330 <211 > 654 <212> DNA <213> Artificial <220> <223> CR6301 Light chain <220> <221 > CDS <222> (1)..(654) <400> 330 gaa att gtg ctg act cag tct cca etc tee ctg ccc gtc acc eet gga 48

Glu Ile Val Leu Thr Gin Ser Pro Leu Ser Leu Pro Val Thr Pro Gly 15 10 15 gag ccg gee tec atc tee tgc agg tet agt cag age etc ctg cat agt 96

Glu Pro Ala Ser Ile Ser Cys Arg Ser Ser Gin Ser Leu Leu His Ser 20 25 30 aat gga tae aac tat ttg gat tgg tac ctg cag aag cca ggg cag tct 144

Asn Gly Tyr Asn Tyr Leu Asp Trp Tyr Leu Gin Lys Pro Gly Gin Ser 35 40 45 cca cag ctc ctg atc tat ttg ggt tct aat egg gcc tee ggg gtc cct 192

Pro Gin Leu Leu Ile Tyr Leu Gly Ser Asn Arg Ala Ser Gly Val Pro 50 55 60 gac agg ttc agt ggc agt gga tea ggc aca gat ttt aca ctg aaa atc 240

Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile 65 70 75 80 age aga gtg gag get gag gat gtt ggg gtt tat tac tgc atg caa get 288

Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Met Gin Ala 85 90 95 eta caa act ccc etc act ttc ggc gga ggg acc aag gtg gag atc aaa 336

Leu Gin Thr Pro Leu Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys 100 105 110 egt gcg gcc gea ccc age gtg ttc atc ttc ccc ccc tee gac gag cag 384

Arg Ala Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gin 115 120 125 ctg aag age ggc acc gcc age gtg gtg tgc ctg ctg aac aac ttc tac 432

Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr 130 135 140 ccc egg gag gcc aag gtg cag tgg aag gtg gac aac gcc ctg cag age 480

Pro Arg Glu Ala Lys Val Gin Trp Lys Val Asp Asn Ala Leu Gin Ser 145 150 155 160 ggc aac age cag gag age gtg acc gag cag gac age aag gac tee acc 528

Gly Asn Ser Gin Glu Ser Val Thr Glu Gin Asp Ser Lys Asp Ser Thr 165 170 175 tac age ctg age age acc etc acc ctg age aag gcc gac tac gag aag 576

Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys 180 185 190 cac aag gtg tac gcc tgc gag gtg acc cac cag ggc ctg age age ccc 624

His Lys Val Tyr Ala Cys Glu Val Thr His Gin Gly Leu Ser Ser Pro 195 200 205 gtg acc aag age ttc aac egg ggc gag tgt 654

Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 210 215 <210> 331 <211 > 218 <212> PRT <213> Artificial <220> <223> Synthetic Construct <400> 331

Glu Ile Val Leu Thr Gin Ser Pro Leu Ser Leu Pro Val Thr Pro Gly 15 10 15

Glu Pro Ala Ser Ile Ser Cys Arg Ser Ser Gin Ser Leu Leu His Ser 20 25 30

Asn Gly Tyr Asn Tyr Leu Asp Trp Tyr Leu Gin Lys Pro Gly Gin Ser 35 40 45

Pro Gin Leu Leu Ile Tyr Leu Gly Ser Asn Arg Ala Ser Gly Val Pro 50 55 60

Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile 65 70 75 80

Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Met Gin Ala 85 90 95

Leu Gin Thr Pro Leu Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys 100 105 110

Arg Ala Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gin 115 120 125

Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr 130 135 140

Pro Arg Glu Ala Lys Val Gin Trp Lys Val Asp Asn Ala Leu Gin Ser 145 150 155 160

Gly Asn Ser Gin Glu Ser Val Thr Glu Gin Asp Ser Lys Asp Ser Thr 165 170 175

Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys 180 185 190

His Lys Val Tyr Ala Cys Glu Val Thr His Gin Gly Leu Ser Ser Pro 195 200 205

Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 210 215 <210> 332 <211> 1353 <212> DNA <213> Artificial <220> <223> CR6327 Heavy chain <220> <221 > CDS <222> (1)..(1353) <400> 332 gag gtg cag ctg gtg gag acc ggg get gag gtg aag aag cct ggg tee 48

Glu Val Gin Leu Val Glu Thr Gly Ala Glu Val Lys Lys Pro Gly Ser 15 10 15 teg gtg aag gtc tee tgc aag gee tet gga ggc acc ttc agg aec cat 96

Ala lie Ser Trp Val Arg Gin Ala Pro Gly Gin Gly Leu Glu Trp Met 35 40 45 gga ggg ate ate get ate ttc gga aca gea aac tae gca eag aag ttc 192

Gly Gly lie lie Ala Ile Phe Gly Thr Ala Asn Tyr Ala Gin Lys Phe 50 55 60 cag ggc aga ate aeg att acc geg gac gaa tee aeg agt aca gee tae 240

Gin Gly Arg lie Thr lie Thr Ala Asp Glu Ser Thr Ser Thr Ala Tyr 65 70 75 80 atg gag ctg age age ctg aga tet gag gac aeg gee gtg tat ttc tgt 288

Ala Arg Gly Ser Gly Tyr His He Ser Thr Pro Phe Asp Asn Trp Gly 100 105 110 cag gga acc ctg gtc acc gtc teg agt get age acc aag ggc ccc age 384

Gin Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser 115 120 125 gtg ttc ccc ctg gee ccc age age aag age aec age ggc ggc aca gee 432

Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala 130 135 140 gee ctg ggc tgc ctg gtg aag gac tae ttc ccc gag ccc gtg acc gtg 480

Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala 165 170 175 gtg ctg cag age age ggc ctg tae age ctg age age gtg gtg acc gtg 576

Val Leu Gin Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val 180 185 190 ccc age age age ctg ggc acc cag acc tae ate tgc aac gtg aac cac 624

Pro Gly Lys 450 <210> 333 <211 > 451 <212> PRT <213> Artificial <220> <223> Synthetic Construct <400> 333

Glu Val Gin Leu Val Glu Thr Gly Ala Glu Val Lys Lys Pro Gly Ser 15 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Arg Thr tiis 20 25 30

Ala Ile Ser Trp Val Arg Gin Ala Pro Gly Gin Gly Leu Glu Trp Met 35 40 45

Gly Gly Ile Ile Ala Ile Phe Gly Thr Ala Asn Tyr Ala Gin Lys Phe 50 55 60

Gin Gly Arg Ile Thr Ile Thr Ala Asp Glu Ser Thr Ser Thr Ala Tyr 65 70 75 80

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Phe Cys 85 90 95

Ala Arg Gly Ser Gly Tyr His Ile Ser Thr Pro Phe Asp Asn Trp Gly 100 105 110

Gin Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser 115 120 125

Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala 130 135 140

Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val 145 150 155 160

Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala 165 170 175

Val Leu Gin Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val 180 185 190

Pro Ser Ser Ser Leu Gly Thr Gin Thr Tyr Ile Cys Asn Val Asn His 195 200 205

Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser Cys 210 215 220

Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly 225 230 235 240

Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met 245 250 255

Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His 260 265 270

Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val 275 280 285

His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gin Tyr Asn Ser Thr Tyr 290 295 300

Arg Val Val Ser Val Leu Thr Val Leu His Gin Asp Trp Leu Asn Gly 305 310 315 320

Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile 325 330 335

Glu Lys Thr Ile Ser Lys Ala Lys Gly Gin Pro Arg Glu Pro Gin Val 340 345 350

Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gin Val Ser 355 360 365

Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu 370 375 380

Trp Glu Ser Asn Gly Gin Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro 385 390 395 400

Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val 405 410 415

Asp Lys Ser Arg Trp Gin Gin Gly Asn Val Phe Ser Cys Ser Val Met 420 425 430

His Glu Ala Leu His Asn His Tyr Thr Gin Lys Ser Leu Ser Leu Ser 435 440 445

Pro Gly Lys 450 <210> 334 <211 > 654 <212> DNA <213> Artificial <220> <223> CR6327 Light chain <220> <221 > CDS <222> (1)..(654) <400> 334 tcc tat gtg ctg act cag cca ccc teg gtg tea gtg gcc cca gga cag 48

Ser Tyr Val Leu Thr Gin Pro Pro Ser Val Ser Val Ala Pro Gly Gin 15 10 15 aeg gcc agg att acc tgt ggg gga aac aac att gga agt aaa ggt gtg 96

Thr Ala Arg Ile Thr Cys Gly Gly Asn Asn Ile Gly Ser Lys Gly Val 20 25 30 cac tgg tac cag cag aag cct ggc cag gcc eet gtg ctg gtc gtc tat 144

Asp Glu Ala Asp Tyr Tyr Cys Gin Val Trp Asp Ser Ser Ser Asp His 85 90 95 gtg gta tte ggc gga ggg acc aag ctg acc gtc eta ggt gcg gcc gea 336

Val Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Ala Ala Ala 100 105 110 ggc cag ccc aag gee get ccc age gtg acc ctg tte ccc ccc tcc tcc 384

Gly Gin Pro Lys Ala Ala Pro Ser Val Thr Leu Phe Pro Pro Ser Ser 115 120 125 gag gag ctg cag gcc aac aag gcc acc ctg gtg tgc etc atc age gac 432

Glu Lys Thr Val Ala Pro Thr Glu Cys Ser 210 215 <210> 335 <211 > 218 <212> PRT <213> Artificial <220> <223> Synthetic Construct <400> 335

Ser Tyr Val Leu Thr Gin Pro Pro Ser Val Ser Val Ala Pro Gly Gin 15 10 15

Thr Ala Arg Ile Thr Cys Gly Gly Asn Asn Ile Gly Ser Lys Gly Val 20 25 30

His Trp Tyr Gin Gin Lys Pro Gly Gin Ala Pro Val Leu Val Val Tyr 35 40 45

Asp Asp Ser Asp Arg Pro Ser Gly Ile Pro Glu Arg Phe Ser Gly Ser 50 55 60

Asn Ser Gly Asn Thr Ala Thr Leu Thr Ile Ser Arg Val Glu Ala Gly 65 70 75 80

Asp Glu Ala Asp Tyr Tyr Cys Gin Val Trp Asp Ser Ser Ser Asp His 85 90 95

Val Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Ala Ala Ala 100 105 110

Gly Gin Pro Lys Ala Ala Pro Ser Val Thr Leu Phe Pro Pro Ser Ser 115 120 125

Glu Glu Leu Gin Ala Asn Lys Ala Thr Leu Val Cys Leu Ile Ser Asp 130 135 140

Phe Tyr Pro Gly Ala Val Thr Val Ala Trp Lys Ala Asp Ser Ser Pro 145 150 155 160

Val Lys Ala Gly Val Glu Thr Thr Thr Pro Ser Lys Gin Ser Asn Asn 165 170 175

Lys Tyr Ala Ala Ser Ser Tyr Leu Ser Leu Thr Pro Glu Gin Trp Lys 180 185 190

Ser His Arg Ser Tyr Ser Cys Gin Val Thr His Glu Gly Ser Thr Val 195 200 205

Glu Lys Thr Val Ala Pro Thr Glu Cys Ser 210 215 <210> 336 <211> 1374 <212> DNA <213> Artificial <220> <223> CR6328 Heavy chain <220> <221 > CDS <222> (1)..(1374) <400> 336 gag gtg cag ctg gtg gag tct ggg get gag gtg aag aag cct ggg tee 48

Glu Val Gin Leu Val Glu Ser Gly Ala Glu Val Lys Lys Pro Gly Ser 15 10 15 teg gtg aag gtc tee tgc aag get tct gga cae ate tte age ggc tat 96

Ala Ile Ser Trp Val Arg Gin Ala Pro Gly Gin Gly Leu Glu Trp Met 35 40 45 gga ggg ate ate cct ate ttt ggt aca aca aac tac gca cag aag tte 192

Gly Gly lie lie Pro lie Phe Gly Thr Thr Asn Tyr Ala Gin Lys Phe 50 55 60 cag ggc aga gtc aeg att acc geg gac caa tee aeg age aca gee tac 240

Ala Arg Val Lys Asp Gly Tyr Cys Thr Leu Thr Ser Cys Pro Val Gly 100 105 110 tgg tac tte gat etc tgg ggc cgt ggc ace ctg gtc act gtc teg agt 384

Trp Tyr Phe Asp Leu Trp Gly Arg Gly Thr Leu Val Thr Val Ser Ser 115 120 125 get age acc aag ggc ccc age gtg tte ccc ctg gee ccc age age aag 432

Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys 130 135 140 age acc age ggc ggc aca gee gee ctg ggc tgc ctg gtg aag gac tac 480

Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr 145 150 155 160 tte ccc gag ccc gtg acc gtg age tgg aac age ggc gee ttg acc age 528

Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser 165 170 175 ggc gtg cac acc tte ccc gee gtg ctg cag age age ggc ctg tac age 576

Gly Val His Thr Phe Pro Ala Val Leu Gin Ser Ser Gly Leu Tyr Ser 180 185 190 ctg age age gtg gtg acc gtg ccc age age age ctg ggc acc cag acc 624

Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gin Thr 195 200 205 tac atc tgc aac gtg aac cac aag ccc age aac acc aag gtg gac aaa €72

Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys 210 215 220 ege gtg gag ccc aag age tgc gac aag acc cae acc tgc ccc ccc tgc 720

Arg Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys 225 230 235 240 eet gcc ccc gag ctg ctg ggc gga ccc tee gtg tte ctg tte ccc ccc 768

Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro 245 250 255 aag ccc aag gac acc etc atg ate age egg acc ccc gag gtg acc tgc 816

Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys 260 265 270 gtg gtg gtg gac gtg age cac gag gac ccc gag gtg aag tte aac tgg 864

Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp 275 280 285 tac gtg gac ggc gtg gag gtg cac aac gcc aag acc aag ccc egg gag 912

Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu 290 295 300 gag cag tac aac age acc tac egg gtg gtg age gtg etc acc gtg ctg 960

Glu Gin Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu 305 310 315 320 cac cag gac tgg ctg aac ggc aag gag tac aag tgc aag gtg age aac 1008

His Gin Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn 325 330 335 aag gcc ctg eet gcc ccc atc gag aag acc atc age aag gcc aag ggc 1056

Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly 340 345 350 cag ccc egg gag ccc cag gtg tac acc ctg ccc ccc age egg gag gag 1104

Gin Pro Arg Glu Pro Gin Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu 355 360 365 atg acc aag aac cag gtg tee etc acc tgt ctg gtg aag ggc tte tac 1152

Met Thr Lys Asn Gin Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr 370 375 380 ccc age gac atc gcc gtg gag tgg gag age aac ggc cag ccc gag aac 1200

Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gin Pro Glu Asn 385 390 395 400 aac tac aag acc acc ccc eet gtg ctg gac age gac ggc age tte tte 1248

Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe 405 410 415 ctg tac age aag etc acc gtg gac aag age egg tgg cag cag ggc aac 1296

Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gin Gin Gly Asn 420 425 430 gtg tte age tgc age gtg atg cac gag gcc ctg cac aac cac tac acc 1344

Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr 435 440 445 cag aag age ctg age ctg age ccc ggc aag 1374

Gin Lys Ser Leu Ser Leu Ser Pro Gly Lys 450 455 <210> 337 <211 >458 <212> PRT <213> Artificial <220> <223> Synthetic Construct <400> 337

Glu Val Gin Leu Val Glu Ser Gly Ala Glu Val Lys Lys Pro Gly Ser 15 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly His Ile Phe Ser Gly Tyr 20 25 30

Ala Ile Ser Trp Val Arg Gin Ala Pro Gly Gin Gly Leu Glu Trp Met 35 40 45

Gly Gly Ile Ile Pro Ile Phe Gly Thr Thr Asn Tyr Ala Gin Lys Phe 50 55 60

Gin Gly Arg Val Thr Ile Thr Ala Asp Gin Ser Thr Ser Thr Ala Tyr 65 70 75 80

Met Asp Leu Ser Asn Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95

Ala Arg Val Lys Asp Gly Tyr Cys Thr Leu Thr Ser Cys Pro Val Gly 100 105 110

Trp Tyr Phe Asp Leu Trp Gly Arg Gly Thr Leu Val Thr Val Ser Ser 115 120 125

Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys 130 135 140

Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr 145 150 155 160

Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser 165 170 175

Gly Val His Thr Phe Pro Ala Val Leu Gin Ser Ser Gly Leu Tyr Ser 180 185 190

Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gin Thr 195 200 205

Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys 210 215 220

Arg Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys 225 230 235 240

Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro 245 250 255

Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys 260 265 270

Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp 275 280 285

Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu 290 295 300

Glu Gin Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu 305 310 315 320

His Gin Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn 325 330 335

Lys Ala Leu Pro Ala Pro ile Glu Lys Thr Ile Ser Lys Ala Lys Gly 340 345 350

Gin Pro Arg Glu Pro Gin Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu 355 360 365

Met Thr Lys Asn Gin Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr 370 375 380

Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gin Pro Glu Asn 385 390 395 400

Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe 405 410 415

Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gin Gin Gly Asn 420 425 430

Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr 435 440 445

Gin Lys Ser Leu Ser Leu Ser Pro Gly Lys 450 455 <210> 338 <211 > 639 <212> DNA <213> Artificial <220> <223> CR6328 Light chain <220> <221 > CDS <222> (1)..(639) <400> 338 gaa att gtg atg acg cag tct cca ggc acc ctg tct ttg tct cca ggg 48

Glu Ile Val Met Thr Gin Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly 15 10 15 gaa aga gcc acc ctc tcg tgc agg gcc agt cag agt gtt age age age 96

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gin Ser Val Ser Ser Ser 20 25 30 tac tta gcc tgg tae cag cag aaa cot gge cag get ccc agg ctc ctc 144

Tyr Leu Ala Trp Tyr Gin Gin Lys Pro Gly Gin Ala Pro Arg Leu Leu 35 40 45 ate ttt ggt gcc tee age agg gcc act ggc atc cca gac agg ttc agt 192

Ile Phe Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser 50 55 60 ggc agt ggg tct ggg aca gac ttc act ctc acc atc age aga ctg gag 240

Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu 65 70 75 80 cct gaa gat ttt gea gtg tat tac tgt cag cag tat ggt age tea ctc 288

Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gin Gin Tyr Gly Ser Ser Leu 85 90 95 act ttc ggc gga ggg acc aag ctg gag atc aaa egt gcg gcc gea ccc 336

Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys Arg Ala Ala Ala Pro 100 105 110 age gtg ttc atc ttc ccc ccc tee gac gag cag ctg aag age ggc acc 384

Val Gin Trp Lys Val Asp Asn Ala Leu Gin Ser Gly Asn Ser Gin Glu 145 150 155 160 age gtg acc gag cag gac age aag gac tee acc tac age ctg age age 528

Asn Arg Gly Glu Cys 210 <210> 339 <211 > 213 <212> PRT <213> Artificial <220> <223> Synthetic Construct <400> 339

Glu Ile Val Met Thr Gin Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly 15 10 15

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gin Ser Val Ser Ser Ser 20 25 30

Tyr Leu Ala Trp Tyr Gin Gin Lys Pro Gly Gin Ala Pro Arg Leu Leu 35 40 45

Ile Phe Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser 50 55 60

Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu 65 70 75 80

Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gin Gin Tyr Gly Ser Ser Leu 85 90 95

Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys Arg Ala Ala Ala Pro 100 105 110

Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gin Leu Lys Ser Gly Thr 115 120 125

Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys 130 135 140

Val Gin Trp Lys Val Asp Asn Ala Leu Gin Ser Gly Asn Ser Gin Glu 145 150 155 160

Ser Val Thr Glu Gin Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser 165 170 175

Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala 180 185 190

Cys Glu Val Thr His Gin Gly Leu Ser Ser Pro Val Thr Lys Ser Phe 195 200 205

Asn Arg Gly Glu Cys 210 <210> 340 <211> 1353 <212> DNA <213> Artificial <220> <223> CR6329 Heavy chain <220> <221 > CDS <222> (1)..(1353) <400> 340 gag gtc cag ctg gta cag tct ggg get gag gtt aag aag cct ggg tee 48

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Ile Phe Arg Ser Asn 20 25 30 tct ate agt tgg gtg ega cag gee cct ggg caa ggg ett gag tgg atg 144

Gly Gly lie Phe Ala Leu Phe Gly Thr Thr Asp Tyr Ala Gin Lys Phe 50 55 60 cag ggc aga gtc aeg att acc geg gac gaa tct teg acc aca gtc tac 240

Ala Arg Gly Ser Gly Tyr Thr Thr Arg Asn Tyr Phe Asp Tyr Trp Gly 100 105 110 cag ggc acc ctg gtc acc gtc teg agt get age acc aag ggc ccc age 384

Gin Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser 115 120 125 gtg ttc ccc ctg gee ccc age age aag age acc age ggc ggc aca gee 432

Pro Ser Ser Ser Leu Gly Thr Gin Thr Tyr He Cys Asn Val Asn His 195 200 205 &&g ccc age aac acc aag gtg gac aaa ege gtg gag ccc aag age tgc 672

Pro Gly Lys 450 <210> 341 <211 >451 <212> PRT <213> Artificial <220> <223> Synthetic Construct <400> 341

Glu Val Gin Leu Val Gin Ser Gly Ala Glu Val Lys Lys Pro Gly Ser 15 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Ile Phe Arg Ser Asn 20 25 30

Ser Ile Ser Trp Val Arg Gin Ala Pro Gly Gin Gly Leu Glu Trp Met 35 40 45

Gly Gly Ile Phe Ala Leu Phe Gly Thr Thr Asp Tyr Ala Gin Lys Phe 50 55 60

Gin Gly Arg Val Thr Ile Thr Ala Asp Glu Ser Ser Thr Thr Val Tyr 65 70 75 80

Leu Glu Leu Ser Ser Leu Thr Ser Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95

Ala Arg Gly Ser Gly Tyr Thr Thr Arg Asn Tyr Phe Asp Tyr Trp Gly 100 105 110

Gin Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser 115 120 125

Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala 130 135 140

Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val 145 150 155 160

Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala 165 170 175

Val Leu Gin Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val 180 185 190

Pro Ser Ser Ser Leu Gly Thr Gin Thr Tyr Ile Cys Asn Val Asn His 195 200 205

Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser Cys 210 215 220

Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly 225 230 235 240

Gly Pro Ser Val Phe Leu Phe Fro Pro Lys Fro Lys Asp Thr Leu Met 245 250 255

Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His 260 265 270

Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val 275 280 285

His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gin Tyr Asn Ser Thr Tyr 290 295 300

Arg Val Val Ser Val Leu Thr Val Leu His Gin Asp Trp Leu Asn Gly 305 310 315 320

Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile 325 330 335

Glu Lys Thr Ile Ser Lys Ala Lys Gly Gin Pro Arg Glu Pro Gin Val 340 345 350

Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gin Val Ser 355 360 365

Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu 370 375 380

Trp Glu Ser Asn Gly Gin Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro 385 390 395 400

Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val 405 410 415

Asp Lys Ser Arg Trp Gin Gin Gly Asn Val Phe Ser Cys Ser Val Met 420 425 430

His Glu Ala Leu His Asn His Tyr Thr Gin Lys Ser Leu Ser Leu Ser 435 440 445

Pro Gly Lys 450 <210> 342 <211 > 654 <212> DNA <213> Artificial <220> <223> CR6329 Light chain <220> <221 > CDS <222> (1)..(654) <400> 342 gaa att gtg ctg act cag tct cca ggc acc ctg tct ttg tct cca ggg 48

Glu Ile Val Leu Thr Gin Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly 15 10 15 gaa aga gcc aca ctc tcc tgc agg gcc agt cag agt gtt age age aac 96

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gin Ser Val Ser Ser Asn 20 25 30 tac tta ggc tgg tae cag cag aaa eet ggc cag get ccc agg ctc ctg 144

Tyr Leu Gly Trp Tyr Gin Gin Lys Pro Gly Gin Ala Pro Arg Leu Leu 35 40 45 atc tat ggt gea tcc age agg gcc agt ggc atc cca gac agg ttc agt 192

Ile Tyr Gly Ala Ser Ser Arg Ala Ser Gly Ile Pro Asp Arg Phe Ser 50 55 60 ggc ggt ggg tct ggg aca gac ttc act ctc acc atc age aga ctg gag 240

Gly Gly Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu 65 70 75 80 cct gaa gat ttt gea gtg tat tac tgt cag cag tat ggt age tea ccc 288

Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gin Gin Tyr Gly Ser Ser Pro 85 90 95 etc act ttc ggc gga ggg acc aag gtg gag atc aaa egt gcg gcc gea 336

Leu Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg Ala Ala Ala 100 105 110 ggc cag ccc aag gcc get ccc age gtg acc ctg ttc ccc ccc tcc tcc 384

Gly Gin Pro Lys Ala Ala Pro Ser Val Thr Leu Phe Pro Pro Ser Ser 115 120 125 gag gag ctg cag gcc aac aag gcc acc ctg gtg tgc ctc atc age gac 432

Glu Glu Leu Gin Ala Asn Lys Ala Thr Leu Val Cys Leu Ile Ser Asp 130 135 140 ttc tac cct ggc gcc gtg acc gtg gcc tgg aag gcc gac age age ccc 480

Val Lys Ala Gly Val Glu Thr Thr Thr Pro Ser Lys Gin Ser Asn Asn 165 170 175 aag tac gcc gcc age age tac ctg age ctc acc ccc gag cag tgg aag 576

Glu Lys Thr Val Ala Pro Thr Glu Cys Ser 210 215 <210> 343 <211> 218 <212> PRT <213> Artificial <220> <223> Synthetic Construct <400> 343

Glu Ile Val Leu Thr Gin Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly 15 10 15

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gin Ser Val Ser Ser Asn 20 25 30

Tyr Leu Gly Trp Tyr Gin Gin Lys Pro Gly Gin Ala Pro Arg Leu Leu 35 40 45

Ile Tyr Gly Ala Ser Ser Arg Ala Ser Gly Ile Pro Asp Arg Phe Ser 50 55 60

Gly Gly Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu 65 70 75 80

Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gin Gin Tyr Gly Ser Ser Pro 85 90 95

Leu Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg Ala Ala Ala 100 105 110

Gly Gin Pro Lys Ala Ala Pro Ser Val Thr Leu Phe Pro Pro Ser Ser 115 120 125

Glu Glu Leu Gin Ala Asn Lys Ala Thr Leu Val Cys Leu Ile Ser Asp 130 135 140

Phe Tyr Pro Gly Ala Val Thr Val Ala Trp Lys Ala Asp Ser Ser Pro 145 150 155 160

Val Lys Ala Gly Val Glu Thr Thr Thr Pro Ser Lys Gin Ser Asn Asn 165 170 175

Lys Tyr Ala Ala Ser Ser Tyr Leu Ser Leu Thr Pro Glu Gin Trp Lys 180 185 190

Ser His Arg Ser Tyr Ser Cys Gin Val Thr His Glu Gly Ser Thr Val 195 200 205

Glu Lys Thr Val Ala Pro Thr Glu Cys Ser 210 215 <210> 344 <211 > 1350 <212> DNA <213> Artificial <220> <223> CR6332 Heavy chain <220> <221 > CDS <222> (1)..(1350) <400> 344 cag gtg cag ctg gtg cag tct ggg get gag gtg aag aag cct ggg tee 48

Gin Val Gin Leu Val Gin Ser Gly Ala Glu Val Lys Lys Pro Gly Ser 15 10 15 teg gta aag gtc tee tgc aag get tct gga ggc ccc tte ege aat ttt 96

Gly Gly Ile Ile Ala Val Phe Gly Thr Thr Lys Tyr Ala His Lys Phe 50 55 60 cag ggc aga gtc acc ate ace geg gac gac tee aca aat aca get tac 240

Met Glu Leu Gly Ser Leu Lys Ser Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 geg aga ggt ccc cac tac tac tee tee tac atg gac gtc tgg ggc gaa 336

Ala Arg Gly Pro His Tyr Tyr Ser Ser Tyr Met Asp Val Trp Gly Glu 100 105 110 ggg acc aeg gtc acc gtc teg agt get age acc aag ggc ccc age gtg 384

Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val 165 170 175 ctg cag age age ggc ctg tac age ctg age age gtg gtg ace gtg ccc 576

Leu Gin Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro 180 185 190 age age age etg ggc acc cag acc tac ate tgc aac gtg aac cac aag 624

Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly 225 230 235 240 ccc tee gtg ttc ctg ttc ccc ccc aag ccc aag gac acc etc atg ate 768

Gly Lys 450 <210> 345 <211 >450 <212> PRT <213> Artificial <220> <223> Synthetic Construct <400> 345

Gin Val Gin Leu Val Gin Ser Gly Ala Glu Val Lys Lys Pro Gly Ser 15 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Pro Phe Arg Asn Phe 20 25 30

Ala lie Asn Trp Val Arg Gin Ala Pro Gly Gin Gly Leu Glu Trp Met 35 40 45

Gly Gly Ile Ile Ala Val Phe Gly Thr Thr Lys Tyr Ala His Lys Phe 50 55 60

Gin Gly Arg Val Thr lie Thr Ala Asp Asp Ser Thr Asn Thr Ala Tyr 65 70 75 80

Met Glu Leu Gly Ser Leu Lys Ser Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95

Ala Arg Gly Pro His Tyr Tyr Ser Ser Tyr Met Asp Val Trp Gly Glu 100 105 110

Gly Thr Thr Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val 115 120 125

Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala 130 135 140

Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser 145 150 155 160

Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val 165 170 175

Leu Gin Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro 180 185 190

Ser Ser Ser Leu Gly Thr Gin Thr Tyr Ile Cys Asn Val Asn His Lys 195 200 205

Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser Cys Asp 210 215 220

Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly 225 230 235 240

Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile 245 250 255

Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu 2€0 265 270

Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His 275 280 285

Asn Ala Lys Thr Lys Pro Arg Glu Glu Gin Tyr Asn Ser Thr Tyr Arg 290 295 300

Val Val Ser Val Leu Thr Val Leu His Gin Asp Trp Leu Asn Gly Lys 305 310 315 320

Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu 325 330 335

Lys Thr Ile Ser Lys Ala Lys Gly Gin Pro Arg Glu Pro Gin Val Tyr 340 345 350

Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gin Val Ser Leu 355 360 365

Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp 370 375 380

Glu Ser Asn Gly Gin Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val 385 390 395 400

Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp 405 410 415

Lys Ser Arg Trp Gin Gin Gly Asn Val Phe Ser Cys Ser Val Met His 420 425 430

Glu Ala Leu His Asn His Tyr Thr Gin Lys Ser Leu Ser Leu Ser Pro 435 440 445

Gly Lys 450 <210> 346 <211 > 636 <212> DNA <213> Artificial <220> <223> CR6332 Light chain <220> <221 > CDS <222> (1)..(636) <400> 346 gac ate cag ttg acc cag tet cca tee tee ctg tet gca tet gta gga 48

Asp lie Gin Leu Thr Gin Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 15 10 15 gac aga gtc acc ate act tgc egg geg agt cag ggc att age act tat 96

Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gin Gly Ile Ser Thr Tyr 20 25 30 tta gee tgg tat cag cag aaa ccc ggg aaa gtt cct aaa etc ctg ate 144

Leu Ala Trp Tyr Gin Gin Lys Pro Gly Lys Val Pro Lys Leu Leu lie 35 40 45 tat get gca tee act ttg caa tea ggg gtc cca tet egg ttc agt ggc 192

Tyr Ala Ala Ser Thr Leu Gin Ser Gly Val Pro Ser Arg Phe Ser Gly 50 55 60 agt gga tet ggg aca gat ttc act etc acc ate age age ctg cag cct 240

Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr lie Ser Ser Leu Gin Pro 65 70 75 80 gaa gat gtt gca act tat tac tgt caa aag tat aac agt gee cct tet 288

Glu Asp Val Ala Thr Tyr Tyr Cys Gin Lys Tyr Asn Ser Ala Pro Ser 85 90 95 ttc ggc cct ggg acc aaa gtg gat ate aaa cgt geg gee gca ccc age 336

Phe Gly Pro Gly Thr Lys Val Asp He Lys Arg Ala Ala Ala Pro Ser 100 105 110 gtg ttc ate ttc ccc ccc tee gac gag cag ctg aag age ggc acc gee 384

Val Phe lie Phe Pro Pro Ser Asp Glu Gin Leu Lys Ser Gly Thr Ala 115 120 125 age gtg gtg tgc ctg ctg aac aac ttc tac ccc egg gag gee aag gtg 432

Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val 130 135 140 cag tgg aag gtg gac aac gee ctg cag age ggc aac age cag gag age 480

Gin Trp Lys Val Asp Asn Ala Leu Gin Ser Gly Asn Ser Gin Glu Ser 145 150 155 160 gtg acc gag cag gac age aag gac tee acc tac age ctg age age acc 528

Val Thr Glu Gin Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr 165 170 175 etc acc ctg age aag gee gac tac gag aag cac aag gtg tac gee tgc 576

Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys 180 185 190 gag gtg acc cac cag ggc ctg age age ccc gtg acc aag age ttc aac 624

Glu Val Thr His Gin Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn 195 200 205 egg ggc gag tgt 636

Arg Gly Glu Cys 210 <210> 347 <211> 212 <212> PRT <213> Artificial <220> <223> Synthetic Construct <400> 347

Asp Ile Gin Leu Thr Gin Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 15 10 15

Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gin Gly Ile Ser Thr Tyr 20 25 30

Leu Ala Trp Tyr Gin Gin Lys Pro Gly Lys Val Pro Lys Leu Leu lie 35 40 45

Tyr Ala Ala Ser Thr Leu Gin Ser Gly Val Pro Ser Arg Phe Ser Gly 50 55 60

Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr lie Ser Ser Leu Gin Pro 65 70 75 80

Glu Asp Val Ala Thr Tyr Tyr Cys Gin Lys Tyr Asn Ser Ala Pro Ser 85 90 95

Phe Gly Pro Gly Thr Lys Val Asp lie Lys Arg Ala Ala Ala Pro Ser 100 105 110

Val Phe lie Phe Pro Pro Ser Asp Glu Gin Leu Lys Ser Gly Thr Ala 115 120 125

Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val 130 135 140

Gin Trp Lys Val Asp Asn Ala Leu Gin Ser Gly Asn Ser Gin Glu Ser 145 150 155 160

Val Thr Glu Gin Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr 165 170 175

Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys 180 185 190

Glu Val Thr His Gin Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn 195 200 205

Arg Gly Glu Cys 210 <210> 348 <211 > 1350 <212> DNA <213> Artificial <220> <223> CR6334 Heavy chain <220> <221 > CDS <222> (1)..(1350) <400> 348 gag gtg cag ctg gtg gag act ggg get gag gtg aag aag cct ggg tee 48

Ser Val Lys Val Pro Cys Lys Ser Ser Gly Ser Pro Phe Arg Ser Asn 20 25 30 get gtc age tgg gtg ega cag gee ccc gga caa ggg ett gag tgg gtg 144

Gly Gly lie Leu Gly Val Phe Gly Ser Pro Ser Tyr Ala Gin Lys Phe 50 55 60 cag ggc aga gtc aeg att ace geg gac gaa tee ace aac aca gtc cac 240

Met Glu Leu Arg Gly Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 geg aga ggt cct ace tac tac tac tee tac atg gac gtc tgg ggc aaa 336

Ala Arg Gly Pro Thr Tyr Tyr Tyr Ser Tyr Met Asp Val Trp Gly Lys 100 105 110 ggg ace aeg gtc acc gtc teg agt get age acc aag ggc ccc age gtg 384

Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser 145 150 155 160 tgg aac age ggc gcc ttg acc age ggc gtg cae acc tte ccc gcc gtg 528

Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gin Val Ser Leu 355 360 365 acc tgt ctg gtg aag ggc tte tac ccc age gac atc gcc gtg gag tgg 1152

Gly Lys 450 <210> 349 <211 >450 <212> PRT <213> Artificial <220> <223> Synthetic Construct <400> 349

Glu Val Gin Leu Val Glu Thr Gly Ala Glu Val Lys Lys Pro Gly Ser 15 10 15

Ser Val Lys Val Pro Cys Lys Ser Ser Gly Ser Pro Phe Arg Ser Asn 20 25 30

Ala Val Ser Trp Val Arg Gin Ala Pro Gly Gin Gly Leu Glu Trp Val 35 40 45

Gly Gly Ile Leu Gly Val Phe Gly Ser Pro Ser Tyr Ala Gin Lys Phe 50 55 60

Gin Gly Arg Val Thr Ile Thr Ala Asp Glu Ser Thr Asn Thr Val His 65 70 75 80

Met Glu Leu Arg Gly Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95

Ala Arg Gly Pro Thr Tyr Tyr Tyr Ser Tyr Met Asp Val Trp Gly Lys 100 105 110

Gly Thr Thr Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val 115 120 125

Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala 130 135 140

Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser 145 150 155 160

Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val 165 170 175

Leu Gin Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro 180 185 190

Ser Ser Ser Leu Gly Thr Gin Thr Tyr Ile Cys Asn Val Asn His Lys 195 200 205

Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser Cys Asp 210 215 220

Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly 225 230 235 240

Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile 245 250 255

Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu 260 265 270

Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His 275 280 285

Asn Ala Lys Thr Lys Pro Arg Glu Glu Gin Tyr Asn Ser Thr Tyr Arg 290 295 300

Val Val Ser Val Leu Thr Val Leu His Gin Asp Trp Leu Asn Gly Lys 305 310 315 320

Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu 325 330 335

Lys Thr Ile Ser Lys Ala Lys Gly Gin Pro Arg Glu Pro Gin Val Tyr 340 345 350

Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gin Val Ser Leu 355 360 365

Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp 370 375 380

Glu Ser Asn Gly Gin Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val 385 390 395 400

Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp 405 410 415

Lys Ser Arg Trp Gin Gin Gly Asn Val Phe Ser Cys Ser Val Met His 420 425 430

Glu Ala Leu His Asn His Tyr Thr Gin Lys Ser Leu Ser Leu Ser Pro 435 440 445

Gly Lys 450 <210> 350 <211 > 654 <212> DNA <213> Artificial <220> <223> CR6334 Light chain <220> <221 > CDS <222> (1)..(654) <400> 350 tcc tat gtg ctg act cag cca ccc teg gag tea gtg gcc cca gga cag 48

Ser Tyr Val Leu Thr Gin Pro Pro Ser Glu Ser Val Ala Pro Gly Gin 15 10 15 aeg gcc agg att acc tgt ggg gga aat aac att gga aga aat agt gtg 96

Thr Ala Arg Ile Thr Cys Gly Gly Asn Asn Ile Gly Arg Asn Ser Val 20 25 30 cac tgg tat cag cag aag cca ggc cag gcc cct gtg ctg gtc gtg tat 144

His Trp Tyr Gin Gin Lys Pro Gly Gin Ala Pro Val Leu Val Val Tyr 35 40 45 gat gat age gac egg ccc tea ggg atc cct gag ega ttt tet ggc tcc 192

Asp Asp Ser Asp Arg Pro Ser Gly Ile Pro Glu Arg Phe Ser Gly Ser 50 55 60 aag tet ggg aac aeg gcc acc ctg att atc age agg gtc gaa gtc ggg 240

Lys Ser Gly Asn Thr Ala Thr Leu Ile Ile Ser Arg Val Glu Val Gly 65 70 75 80 gat gag gee gac tac tac tgt cag gtg tgg cat agt agt agt gat cat 288

Asp Glu Ala Asp Tyr Tyr Cys Gin Val Trp His Ser Ser Ser Asp His 85 90 95 tat gtc tte gga act ggg acc aag gtc acc gtc eta ggt gcg gcc gea 336

Tyr Val Phe Gly Thr Gly Thr Lys Val Thr Val Leu Gly Ala Ala Ala 100 105 110 ggc cag ccc aag gee get ccc age gtg acc ctg tte ccc ccc tcc tcc 384

Glu Lys Thr Val Ala Pro Thr Glu Cys Ser 210 215 <210> 351 <211> 218 <212> PRT <213> Artificial <220> <223> Synthetic Construct <400> 351

Ser Tyr Val Leu Thr Gin Pro Pro Ser Glu Ser Val Ala Pro Gly Gin 15 10 15

Thr Ala Arg Ile Thr Cys Gly Gly Asn Asn Ile Gly Arg Asn Ser Val 20 25 30

His Trp Tyr Gin Gin Lys Pro Gly Gin Ala Pro Val Leu Val Val Tyr 35 40 45

Asp Asp Ser Asp Arg Pro Ser Gly Ile Pro Glu Arg Phe Ser Gly Ser 50 55 60

Lys Ser Gly Asn Thr Ala Thr Leu Ile Ile Ser Arg Val Glu Val Gly 65 70 75 80

Asp Glu Ala Asp Tyr Tyr Cys Gin Val Trp His Ser Ser Ser Asp His 85 90 95

Tyr Val Phe Gly Thr Gly Thr Lys Val Thr Val Leu Gly Ala Ala Ala 100 105 110

Gly Gin Pro Lys Ala Ala Pro Ser Val Thr Leu Phe Pro Pro Ser Ser 115 120 125

Glu Glu Leu Gin Ala Asn Lys Ala Thr Leu Val Cys Leu Ile Ser Asp 130 135 140

Phe Tyr Pro Gly Ala Val Thr Val Ala Trp Lys Ala Asp Ser Ser Pro 145 150 155 160

Val Lys Ala Gly Val Glu Thr Thr Thr Pro Ser Lys Gin Ser Asn Asn 165 170 175

Lys Tyr Ala Ala Ser Ser Tyr Leu Ser Leu Thr Pro Glu Gin Trp Lys 180 185 190

Ser His Arg Ser Tyr Ser Cys Gin Val Thr His Glu Gly Ser Thr Val 195 200 205

Glu Lys Thr Val Ala Pro Thr Glu Cys Ser 210 215 <210> 352 <211 > 1350 <212> DNA <213> Artificial <220> <223> CR6336 Heavy chain <220> <221 > CDS <222> (1)..(1350) <400> 352 cag atg cag ctg gta caa tct gga get gag gtg aag aag cct ggg tee 48

Gin Met Gin Leu Val Gin Ser Gly Ala Glu Val Lys Lys Pro Gly Ser 1 5 10 15 teg gtg aag gtc tee tgc aag get tct gga ggc ace ttc age age tat 96

Ala Arg Ser Ser Gly Tyr Tyr Pro Gin Tyr Phe Gin Asp Trp Gly Gin 100 105 110 ggc acc ctg gtc acc gtc teg agt get age acc aag ggc ccc age gtg 384

Gly Lys 450 <210> 353 <211 >450 <212> PRT <213> Artificial <220> <223> Synthetic Construct <400> 353

Gin Met Gin Leu Val Gin Ser Gly Ala Glu Val Lys Lys Pro Gly Ser 15 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Ser Ser Tyr 20 25 30

Ala Ile Ser Trp Val Arg Gin Ala Pro Gly Gin Gly Leu Glu Trp Met 35 40 45

Gly Gly lie Phe Gly Met Phe Gly Thr Ala Asn Tyr Ala Gin Lys Phe 50 55 60

Gin Gly Arg Val Thr lie Thr Ala Asp Glu Phe Thr Ser Ala Ala Tyr 65 70 75 80

Met Glu Leu Ser Ser Leu Gly Ser Glu Asp Thr Ala Met Tyr Tyr Cys 85 90 95

Ala Arg Ser Ser Gly Tyr Tyr Pro Gin Tyr Phe Gin Asp Trp Gly Gin 100 105 110

Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val 115 120 125

Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala 130 135 140

Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser 145 150 155 160

Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val 165 170 175

Leu Gin Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro 180 185 190

Ser Ser Ser Leu Gly Thr Gin Thr Tyr Ile Cys Asn Val Asn His Lys 195 200 205

Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser Cys Asp 210 215 220

Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly 225 230 235 240

Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile 245 250 255

Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu 260 265 270

Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His 275 280 285

Asn Ala Lys Thr Lys Pro Arg Glu Glu Gin Tyr Asn Ser Thr Tyr Arg 290 295 300

Val Val Ser Val Leu Thr Val Leu His Gin Asp Trp Leu Asn Gly Lys 305 310 315 320

Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu 325 330 335

Lys Thr Ile Ser Lys Ala Lys Gly Gin Pro Arg Glu Pro Gin Val Tyr 340 345 350

Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gin Val Ser Leu 355 360 365

Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp 370 375 380

Glu Ser Asn Gly Gin Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val 385 390 395 400

Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp 405 410 415

Lys Ser Arg Trp Gin Gin Gly Asn Val Phe Ser Cys Ser Val Met His 420 425 430

Glu Ala Leu His Asn His Tyr Thr Gin Lys Ser Leu Ser Leu Ser Pro 435 440 445

Gly Lys 450 <210> 354 <211 > 642 <212> DNA <213> Artificial <220> <223> CR6336 Light chain <220> <221 > CDS <222> (1)..(642) <400> 354 gaa att gtg atg aca cag tct cca ggc acc ctg tct ttg tct cca ggg 48

Glu Ile Val Met Thr Gin Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly 15 10 15 caa aga gcc acc ctc tcc tgc agg gcc agt cag agt gtt age age age 96

Gin Arg Ala Thr Leu Ser Cys Arg Ala Ser Gin Ser Val Ser Ser Ser 20 25 30 tac tta gcc tgg tac cag cag aaa cct ggc cag get ccc aga ctc ctc 144

Tyr Leu Ala Trp Tyr Gin Gin Lys Pro Gly Gin Ala Pro Arg Leu Leu 35 40 45 atg tat ggt gea tcc age agg gcc act ggc atc cca gac agg ttc agt 192

Met Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser 50 55 60 ggc agt ggg tct ggg aca gac ttc act ctc acc atc age aga ctg gag 240

Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu 65 70 75 80 cct gaa gat ttt gea gtg tat tac tgt cag cag tat ggt age tea teg 288

Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gin Gin Tyr Gly Ser Ser Ser 85 90 95 etc act ttc ggc gga ggg acc aag ctg gag atc aaa egt gcg gcc gea 336

Leu Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys Arg Ala Ala Ala 100 105 110 ccc age gtg ttc atc ttc ccc ccc tcc gac gag cag ctg aag age ggc 384

Phe Asn Arg Gly Glu Cys 210 <210> 355 <211 > 214 <212> PRT <213> Artificial <220> <223> Synthetic Construct <400> 355

Glu Ile Val Met Thr Gin Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly 15 10 15

Gin Arg Ala Thr Leu Ser Cys Arg Ala Ser Gin Ser Val Ser Ser Ser 20 25 30

Tyr Leu Ala Trp Tyr Gin Gin Lys Pro Gly Gin Ala Pro Arg Leu Leu 35 40 45

Met Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser 50 55 60

Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu 65 70 75 80

Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gin Gin Tyr Gly Ser Ser Ser 85 90 95

Leu Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys Arg Ala Ala Ala 100 105 110

Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gin Leu Lys Ser Gly 115 120 125

Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala 130 135 140

Lys Val Gin Trp Lys Val Asp Asn Ala Leu Gin Ser Gly Asn Ser Gin 145 150 155 160

Glu Ser Val Thr Glu Gin Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser 165 170 175

Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr 180 185 190

Ala Cys Glu Val Thr His Gin Gly Leu Ser Ser Pro Val Thr Lys Ser 195 200 205

Phe Asn Arg Gly Glu Cys 210 <210> 356 <211> 1353 <212> DNA <213> Artificial <220> <223> CR6339 Heavy chain <220> <221 > CDS <222> (1)..(1353) <400> 356 gag gtg cag ctg gtg gag tcc ggg get gag gtg aag aag cct ggg tee 48

Glu Val Gin Leu Val Glu Ser Gly Ala Glu Val Lys Lys Pro Gly Ser 15 10 15 teg gtg aag gtc tec tgc aag get tet gga ggc ate tte aac agt tat 96

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Ile Phe Asn Ser Tyr 20 25 30 get ate age tgg gtg ega cag gee cct gga caa ggg ett gag tgg atg 144

Ala Ile Ser Trp Val Arg Gin Ala Pro Gly Gin Gly Leu Glu Trp Met 35 40 45 gga ggc ate ate get ate ttt cat aca cca aag tac gca cag aag ttc 192

Gly Gly lie lie Ala lie Phe His Thr Pro Lys Tyr Ala Gin Lys Phe 50 55 60 cag ggc aga gtc aeg att acc geg gac gaa tec aeg aac aca gee tac 240

Gin Gly Arg Val Thr lie Thr Ala Asp Glu Ser Thr Asn Thr Ala Tyr 65 70 75 80 atg gaa ctg aga age ctg aaa tet gag gac aeg gee ctg tat tac tgt 288

Met Glu Leu Arg Ser Leu Lys Ser Glu Asp Thr Ala Leu Tyr Tyr Cys 85 90 95 geg aga ggg tec act tac gat ttt teg agt ggc ett gac tac tgg ggc 336

Ala Arg Gly Ser Thr Tyr Asp Phe Ser Ser Gly Leu Asp Tyr Trp Gly 100 105 110 cag gga acc ctg gtc acc gtc teg agt get age acc aag ggc ccc age 384

Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser Cys 210 215 220 gac aag acc cac ace tgc ccc ccc tgc cct gee ccc gag ctg ctg ggc 720

Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly 225 230 235 240 gga ccc tec gtg ttc ctg ttc ccc ccc aag ccc aag gac acc etc atg 768

Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro He 325 330 335 gag aag acc ate age aag gee aag ggc cag ccc egg gag ccc cag gtg 1056

Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp He Ala Val Glu 370 375 380 tgg gag age aac ggc cag ccc gag aac aac tac aag acc acc ccc cct 1200

Pro Gly Lys 450 <210> 357 <211 > 451 <212> PRT <213> Artificial <220> <223> Synthetic Construct <400> 357

Glu Val Gin Leu Val Glu Ser Gly Ala Glu Val Lys Lys Pro Gly Ser 15 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Ile Phe Asn Ser Tyr 20 25 30

Ala Ile Ser Trp Val Arg Gin Ala Pro Gly Gin Gly Leu Glu Trp Met 35 40 45

Gly Gly Ile Ile Ala Ile Phe His Thr Pro Lys Tyr Ala Gin Lys Phe 50 55 60

Gin Gly Arg Val Thr Ile Thr Ala Asp Glu Ser Thr Asn Thr Ala Tyr 65 70 75 80

Met Glu Leu Arg Ser Leu Lys Ser Glu Asp Thr Ala Leu Tyr Tyr Cys 85 90 95

Ala Arg Gly Ser Thr Tyr Asp Phe Ser Ser Gly Leu Asp Tyr Trp Gly 100 105 110

Gin Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser 115 120 125

Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala 130 135 140

Ala Leu Gly Cys Leu Val Lys Asp Tyr Fhe Pro Glu Pro Val Thr Val 145 150 155 160

Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala 165 170 175

Val Leu Gin Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val 180 185 190

Pro Ser Ser Ser Leu Gly Thr Gin Thr Tyr lie Cys Asn Val Asn His 195 200 205

Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser Cys 210 215 220

Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly 225 230 235 240

Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val 275 280 285

His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gin Tyr Asn Ser Thr Tyr 290 295 300

Arg Val Val Ser Val Leu Thr Val Leu His Gin Asp Trp Leu Asn Gly 305 310 315 320

Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro lie 325 330 335

Glu Lys Thr lie Ser Lys Ala Lys Gly Gin Pro Arg Glu Fro Gin Val 340 345 350

Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gin Val Ser 355 360 365

Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp lie Ala Val Glu 370 375 380

Trp Glu Ser Asn Gly Gin Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro 385 390 395 400

Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val 405 410 415

Asp Lys Ser Arg Trp Gin Gin Gly Asn Val Phe Ser Cys Ser Val Met 420 425 430

His Glu Ala Leu His Asn His Tyr Thr Gin Lys Ser Leu Ser Leu Ser 435 440 445

Pro Gly Lys 450 <210> 358 <211 > 654 <212> DNA <213> Artificial <220> <223> CR6339 Light chain <220> <221 > CDS <222> (1)..(654) <400> 358 cag gca ggg ctg act cag cca ccc teg gtg tea gtg gee cca gga cag 48

Gin Ala Gly Leu Thr Gin Pro Pro Ser Val Ser Val Ala Pro Gly Gin 15 10 15 aeg gee agg att ace tgt ggg gga aac aae att gga agt aaa agt gtg 96

Thr Ala Arg Ile Thr Cys Gly Gly Asn Asn Ile Gly Ser Lys Ser Val 20 25 30 cac tgg tac cag cag aag cca ggc cag gee cct gtc eta gtc gtc tat 144

His Trp Tyr Gin Gin Lys Pro Gly Gin Ala Pro Val Leu Val Val Tyr 35 40 45 gat gat age gac egg ccc tea ggg ate cct gag ega ttc tet ggc tee 192

Asp Asp Ser Asp Arg Pro Ser Gly lie Pro Glu Arg Phe Ser Gly Ser 50 55 60 aac tet ggg aac aeg gee ace ctg acc ate age agg gtc gaa gee ggg 240

Asn Ser Gly Asn Thr Ala Thr Leu Thr lie Ser Arg Val Glu Ala Gly 65 70 75 80 gat gag gee gac tat tac tgt cag gtg tgg gat agt agt agt gat eat 288

Asp Glu Ala Asp Tyr Tyr Cys Gin Val Trp Asp Ser Ser Ser Asp His 85 90 95 gtg gta ttc ggc gga ggg acc aag ctg acc gtc eta ggt geg gee gca 336

Val Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Ala Ala Ala 100 105 110 ggc cag ccc aag gee get ccc age gtg acc ctg ttc ccc ccc tee tec 384

Glu Lys Thr Val Ala Pro Thr Glu Cys Ser 210 215 <210> 359 <211 > 218 <212> PRT <213> Artificial <220> <223> Synthetic Construct <400> 359

Gin Ala Gly Leu Thr Gin Pro Pro Ser Val Ser Val Ala Pro Gly Gin 15 10 15

Thr Ala Arg Ile Thr Cys Gly Gly Asn Asn Ile Gly Ser Lys Ser Val 20 25 30

His Trp Tyr Gin Gin Lys Pro Gly Gin Ala Pro Val Leu Val Val Tyr 35 40 45

Asp Asp Ser Asp Arg Pro Ser Gly lie Pro Glu Arg Phe Ser Gly Ser 50 55 60

Asn Ser Gly Asn Thr Ala Thr Leu Thr lie Ser Arg Val Glu Ala Gly 65 70 75 80

Asp Glu Ala Asp Tyr Tyr Cys Gin Val Trp Asp Ser Ser Ser Asp His 85 90 95

Val Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Ala Ala Ala 100 105 110

Gly Gin Pro Lys Ala Ala Pro Ser Val Thr Leu Phe Pro Pro Ser Ser 115 120 125

Glu Glu Leu Gin Ala Asn Lys Ala Thr Leu Val Cys Leu lie Ser Asp 130 135 140

Phe Tyr Pro Gly Ala Val Thr Val Ala Trp Lys Ala Asp Ser Ser Pro 145 150 155 160

Val Lys Ala Gly Val Glu Thr Thr Thr Pro Ser Lys Gin Ser Asn Asn 165 170 175

Lys Tyr Ala Ala Ser Ser Tyr Leu Ser Leu Thr Pro Glu Gin Trp Lys 180 185 190

Ser His Arg Ser Tyr Ser Cys Gin Val Thr His Glu Gly Ser Thr Val 195 200 205

Glu Lys Thr Val Ala Pro Thr Glu Cys Ser 210 215 <210> 360 <211> 1368 <212> DNA <213> Artificial <220> <223> CR6342 Heavy chain <220> <221 > CDS <222> (1)..(1368) <400> 360 cag gtc cag ctg gtg cag tct ggg get gag gtg aag aag cct ggg tee 48

Gin Val Gin Leu Val Gin Ser Gly Ala Glu Val Lys Lys Pro Gly Sen 15 10 15 teg gtg aag gtc tee tgc aag get tct gga ggc ttc ttc age age tat 96

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Phe Phe Ser Ser Tyr 20 25 30 get ate age tgg gtg ege cag gee cct gga caa gga ett gag tgg atg 144

Gly Gly Val lie Pro lie Phe Arg Thr Ala Asn Tyr Ala Gin Asn Phe 50 55 60 cag ggc aga gtc ace att acc geg gac gaa ttc aca teg tat atg gag 240

Leu Asn Tyr His Asp Ser Gly Thr Tyr Tyr Asn Ala Pro Arg Gly Trp 100 105 110 ttc gac ccc tgg ggc cag gga acc ctg gtc acc gtc teg agt get age 384

Phe Asp Pro Trp Gly Gin Gly Thr Leu Val Thr Val Ser Ser Ala Ser 115 120 125 acc aag ggc ccc age gtg ttc ccc ctg gee ccc age age aag age acc 432

Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr 130 135 140 age ggc ggc aca gee gee ctg ggc tgc ctg gtg aag gac tac ttc ccc 480

Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro 145 150 155 160 gag ccc gtg acc gtg age tgg aac age ggc gee ttg acc age ggc gtg 528

Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val 165 170 175 cac acc ttc ccc gee gtg ctg cag age age ggc ctg tac age ctg age 576

His Thr Phe Pro Ala Val Leu Gin Ser Ser Gly Leu Tyr Ser Leu Ser 180 185 190 age gtg gtg acc gtg ccc age age age ctg ggc acc cag acc tac ate 624

Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gin Thr Tyr He 195 200 205 tgc aac gtg aac cac aag ccc age aac ace aag gtg gac aaa ege gtg 672

Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val 210 215 220 gag ccc aag age tgc gac aag acc cac acc tgc ccc ccc tgc cct gee 720

Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala 225 230 235 240 ccc gag ctg ctg ggc gga ccc tee gtg ttc ctg ttc ccc ccc aag ccc 768

Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro 245 250 255 aag gac acc etc atg ate age egg acc ccc gag gtg acc tgc gtg gtg 816

Lys Asp Thr Leu Met lie Ser Arg Thr Pro Glu Val Thr Cys Val Val 260 265 270 gtg gac gtg age cac gag gac ccc gag gtg aag ttc aac tgg tac gtg 864

Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val 275 280 285 gac ggc gtg gag gtg cac aac gee aag acc aag ccc egg gag gag cag 912

Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gin 290 295 300 tac aac age acc tac egg gtg gtg age gtg etc acc gtg ctg cac cag 960

Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gin 305 310 315 320 gac tgg ctg aac ggc aag gag tac aag tgc aag gtg age aac aag gee 1006

Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala 325 330 335 ctg cct gee ccc ate gag aag acc ate age aag gee aag- ggc cag ccc 1056

Leu Pro Ala Pro lie Glu Lys Thr lie Ser Lys Ala Lys Gly Gin Pro 340 345 350 egg gag ccc cag gtg tac acc ctg ccc ccc age egg gag gag atg acc 1104

Arg Glu Pro Gin Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr 355 360 365 aag aac cag gtg tee etc acc tgt ctg gtg aag ggc ttc tac ccc age 1152

Lys Asn Gin Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser 370 375 380 gac atc gcc gtg gag tgg gag age aac ggc cag ccc gag aac aac tac 1200

Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gin Pro Glu Asn Asn Tyr 385 390 395 400 aag acc acc ccc cct gtg ctg gac age gac ggc age tte tte ctg tac 1248

Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr 405 410 415 age aag etc acc gtg gac aag age egg tgg cag cag ggc aac gtg tte 1296

Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gin Gin Gly Asn Val Phe 420 425 430 age tgc age gtg atg cac gag gcc ctg cac aac cac tac acc cag aag 1344

Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gin Lys 435 440 445 age ctg age ctg age ccc ggc aag 1368

Ser Leu Ser Leu Ser Pro Gly Lys 450 455 <210> 361 <211 >456 <212> PRT <213> Artificial <220> <223> Synthetic Construct <400> 361

Gin Val Gin Leu Val Gin Ser Gly Ala Glu Val Lys Lys Pro Gly Ser 15 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Phe Phe Ser Ser Tyr 20 25 30

Ala Ile Ser Trp Val Arg Gin Ala Pro Gly Gin Gly Leu Glu Trp Met 35 40 45

Gly Gly Val Ile Pro Ile Phe Arg Thr Ala Asn Tyr Ala Gin Asn Phe 50 55 60

Gin Gly Arg Val Thr Ile Thr Ala Asp Glu Phe Thr Ser Tyr Met Glu 65 70 75 80

Leu Ser Ser Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys Ala Arg 85 90 95

Leu Asn Tyr His Asp Ser Gly Thr Tyr Tyr Asn Ala Pro Arg Gly Trp 100 105 110

Phe Asp Pro Trp Gly Gin Gly Thr Leu Val Thr Val Ser Ser Ala Ser 115 120 125

Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr 130 135 140

Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro 145 150 155 160

Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val 165 170 175

His Thr Phe Pro Ala Val Leu Gin Ser Ser Gly Leu Tyr Ser Leu Ser 180 185 190

Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gin Thr Tyr Ile 195 200 205

Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val 210 215 220

Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala 225 230 235 240

Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro 245 250 255

Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val 260 265 270

Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val 275 280 285

Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gin 290 295 300

Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gin 305 310 315 320

Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala 325 330 335

Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gin Pro 340 345 350

Arg Glu Pro Gin Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr 355 360 365

Lys Asn Gin Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser 370 375 380

Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gin Pro Glu Asn Asn Tyr 385 390 395 400

Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr 405 410 415

Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gin Gin Gly Asn Val Phe 420 425 430

Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gin Lys 435 440 445

Ser Leu Ser Leu Ser Pro Gly Lys 450 455 <210> 362 <211 > 657 <212> DNA <213> Artificial <220> <223> CR6342 Light chain <220>

<221 > CDS <222> (1)..(657) <400> 362 gac ate cag atg acc cag tct cca gac tcc ctg get gtg tet ctg ggc 48

Asp Ile Gin Met Thr Gin Ser Pro Asp Ser Leu Ala Val Ser Leu Gly 15 10 15 gag aag gcc acc atc aac tgc aag tcc age cag agt att tta aac age 96

Glu Lys Ala Thr Ile Asn Cys Lys Ser Ser Gin Ser Ile Leu Asn Ser 20 25 30 tcc aac aat aag aac tac tta get tgg tac cag cag aaa cca gga cag 144

Ser Asn Asn Lys Asn Tyr Leu Ala Trp Tyr Gin Gin Lys Pro Gly Gin 35 40 45 cct cct aag ctg ctc att tac tgg gea tct acc egg gaa tcc ggg gtc 192

Pro Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg Glu Ser Gly Val 50 55 60 cct gac ega ttc agt ggc age ggg tct ggg aca gat tte act etc acc 240

Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr 65 70 75 80 atc age age ctg cag get gaa gat gtg gea gtt tat tac tgt cag caa 288

Ile Ser Ser Leu Gin Ala Glu Asp Val Ala Val Tyr Tyr Cys Gin Gin 85 90 95 tat tat agt agt ccg ccg aeg tte ggc caa ggg acc aag gtg gaa atc 336

Tyr Tyr Ser Ser Pro Pro Thr Phe Gly Gin Gly Thr Lys Val Glu Ile 100 105 110 aaa egt gcg gcc gea ccc age gtg tte atc tte ccc ccc tcc gac gag 384

Lys Arg Ala Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu 115 120 125 cag ctg aag age ggc acc gcc age gtg gtg tgc ctg ctg aac aac tte 432

Tyr Pro Arg Glu Ala Lys Val Gin Trp Lys Val Asp Asn Ala Leu Gin 145 150 155 160 age ggc aac age cag gag age gtg acc gag cag gac age aag gac tcc 528

Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gin Gly Leu Ser Ser 195 200 205 ccc gtg acc aag age tte aac egg ggc gag tgt 657

Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 210 215 <210> 363 <211 > 219 <212> PRT <213> Artificial <220> <223> Synthetic Construct <400> 363

Asp Ile 61n Met Thr Gin Ser Pro Asp Ser Leu Ala Val Ser Leu Gly 15 10 15

Glu Lys Ala Thr Ile Asn Cys Lys Ser Ser Gin Ser lie Leu Asn Ser 20 25 30

Ser Asn Asn Lys Asn Tyr Leu Ala Trp Tyr Gin Gin Lys Pro Gly Gin 35 40 45

Pro Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg Glu Ser Gly Val 50 55 €0

Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr 65 70 75 80 lie Ser Ser Leu Gin Ala Glu Asp Val Ala Val Tyr Tyr Cys Gin Gin 85 90 95

Tyr Tyr Ser Ser Pro Pro Thr Phe Gly Gin Gly Thr Lys Val Glu lie 100 105 110

Lys Arg Ala Ala Ala Pro Ser Val Phe lie Phe Pro Pro Ser Asp Glu 115 120 125

Gin Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe 130 135 140

Tyr Pro Arg Glu Ala Lys Val Gin Trp Lys Val Asp Asn Ala Leu Gin 145 150 155 160

Ser Gly Asn Ser Gin Glu Ser Val Thr Glu Gin Asp Ser Lys Asp Ser 165 170 175

Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu 180 185 190

Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gin Gly Leu Ser Ser 195 200 205

Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 210 215 <210> 364 <211 > 1350 <212> DNA <213> Artificial <220> <223> CR6343 Heavy chain <220> <221 > CDS <222> (1)..(1350) <400> 364 cag gtc cag ctg gtg cag tct gga get gag gtg aag aag cct ggg tee 48

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Val Thr Phe Ser Tyr Tyr 20 25 30 get atg age tgg gtg ega cag gee cct gga caa ggg ett gag tgg atg 144

Ala Arg Ser Ser Asn Tyr Tyr Asp Ser Val Tyr Asp Tyr Trp Gly Gin 100 105 110 gga acc ctg gtc acc gtc teg agt get age acc aag ggc ccc age gtg 384

Gly Lys 450 <210> 365 <211 >450 <212> PRT <213> Artificial <220> <223> Synthetic Construct <400> 365

Gin Val Gin Leu Val Gin Ser Gly Ala Glu Val Lys Lys Pro Gly Ser 15 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Val Thr Phe Ser Tyr Tyr 20 25 30

Ala Met Ser Trp Val Arg Gin Ala Pro Gly Gin Gly Leu Glu Trp Met 35 40 45

Gly Gly Ile Ser Pro Met Phe Gly Thr Thr Thr Tyr Ala Gin Lys Phe 50 55 60

Gin Gly Arg Val Thr Ile Thr Ala Asp Asp Ser Thr Ser Thr Ala Tyr 65 70 75 80

Met Glu Val Arg Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95

Ala Arg Ser Ser Asn Tyr Tyr Asp Ser Val Tyr Asp Tyr Trp Gly Gin 100 105 110

Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val 115 120 125

Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala 130 135 140

Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser 145 150 155 160

Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala val 165 170 175

Leu Gin Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro 180 185 190

Ser Ser Ser Leu Gly Thr Gin Thr Tyr Ile Cys Asn Val Asn His Lys 195 200 205

Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser Cys Asp 210 215 220

Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly 225 230 235 240

Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile 245 250 255

Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu 260 265 270

Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His 275 280 285

Asn Ala Lys Thr Lys Pro Arg Glu Glu Gin Tyr Asn Ser Thr Tyr Arg 290 295 300

Val Val Ser Val Leu Thr Val Leu His Gin Asp Trp Leu Asn Gly Lys 305 310 315 320

Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu 325 330 335

Lys Thr Ile Ser Lys Ala Lys Gly Gin Pro Arg Glu Pro Gin Val Tyr 340 345 350

Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gin Val Ser Leu 355 360 365

Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp 370 375 380

Glu Ser Asn Gly Gin Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val 385 390 395 400

Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp 405 410 415

Lys Ser Arg Trp Gin Gin Gly Asn Val Phe Ser Cys Ser Val Met His 420 425 430

Glu Ala Leu Kis Asn His Tyr Thr Gin Lys Ser Leu Ser Leu Ser Pro 435 440 445

Gly Lys 450 <210> 366 <211 > 654 <212> DNA <213> Artificial <220> <223> CR6343 Light chain <220> <221 > CDS <222> (1)..(654) <400> 366 cag tct gtc gtg acg cag ccg ccc teg gag tea gtg gcc cca gga cag 48

Gin Ser Val Val Thr Gin Pro Pro Ser Glu Ser Val Ala Pro Gly Gin 15 10 15 acg gcc agg att acc tgt ggg gga cat aac att gga agt aat agt gtg 96

Thr Ala Arg Ile Thr Cys Gly Gly His Asn Ile Gly Ser Asn Ser Val 20 25 30 cac tgg tac cag cag aag cca ggc cag gcc cct gtg ctg gtc gtg tat 144

Kis Trp Tyr Gin Gin Lys Pro Gly Gin Ala Pro Val Leu Val Val Tyr 35 40 45 gat aat age gac egg ccc tea ggg atc cct gag ega tte tct ggc tee 192

Asp Asn Ser Asp Arg Pro Ser Gly Ile Pro Glu Arg Phe Ser Gly Ser 50 55 60 aac tct ggg aac acg gcc acc ctg acc atc age agg gtc gaa gcc ggg 240

Asn Ser Gly Asn Thr Ala Thr Leu Thr Ile Ser Arg Val Glu Ala Gly 65 70 75 80 gat gag gcc gac tat tac tgt cag gtg tgg ggt agt agt agt gac cat 288

Asp Glu Ala Asp Tyr Tyr Cys Gin Val Trp Gly Ser Ser Ser Asp His 85 90 95 tat gtc tte gga act ggg acc aag gtc acc gtc eta ggt gcg gcc gea 336

Tyr Val Phe Gly Thr Gly Thr Lys Val Thr Val Leu Gly Ala Ala Ala 100 105 110 ggc cag ccc aag gee get ccc age gtg acc ctg tte ccc ccc tee tee 384

Glu Lys Thr Val Ala Pro Thr Glu Cys Ser 210 215 <210> 367 <211> 218 <212> PRT <213> Artificial <220> <223> Synthetic Construct <400> 367

Gin Ser Val Val Thr Gin Pro Pro Ser Glu Ser Val Ala Pro Gly Gin 15 10 15

Thr Ala Arg Ile Thr Cys Gly Gly His Asn Ile Gly Ser Asn Ser Val 20 25 30

His Trp Tyr Gin Gin Lys Pro Gly Gin Ala Pro Val Leu Val Val Tyr 35 40 45

Asp Asn Ser Asp Arg Pro Ser Gly Ile Pro Glu Arg Phe Ser Gly Ser 50 55 60

Asn Ser Gly Asn Thr Ala Thr Leu Thr Ile Ser Arg Val Glu Ala Gly 65 70 75 80

Asp Glu Ala Asp Tyr Tyr Cys Gin Val Trp Gly Ser Ser Ser Asp His 85 90 95

Tyr Val Phe Gly Thr Gly Thr Lys Val Thr Val Leu Gly Ala Ala Ala 100 105 110

Gly Gin Pro Lys Ala Ala Pro Ser Val Thr Leu Phe Pro Pro Ser Ser 115 120 125

Glu Glu Leu Gin Ala Asn Lys Ala Thr Leu Val Cys Leu Ile Ser Asp 130 135 140

Phe Tyr Pro Gly Ala Val Thr Val Ala Trp Lys Ala Asp Ser Ser Pro 145 150 155 160

Val Lys Ala Gly Val Glu Thr Thr Thr Pro Ser Lys Gin Ser Asn Asn 165 170 175

Lys Tyr Ala Ala Ser Ser Tyr Leu Ser Leu Thr Pro Glu Gin Trp Lys 180 185 190

Ser His Arg Ser Tyr Ser Cys Gin Val Thr His Glu Gly Ser Thr Val 195 200 205

Glu Lys Thr Val Ala Pro Thr Glu Cys Ser 210 215

<210> 368 <211 > 12 <212> PRT <213> Influenza A virus <400> 368

Gly Val Thr Asn Lys Val Asn Ser Ile Ile Asp Lys 15 10

<210> 369 <211 > 12 <212> PRT <213> Influenza A virus <400> 369

Gly Val Thr Asn Lys Val Asn Ser Ile Ile Asn Lys 15 10

<210> 370 <211 > 12 <212> PRT <213> Influenza A virus <400> 370

Gly Val Thr Asn Lys Glu Asn Ser Ile Ile Asp Lys 15 10 <210> 371

<211 > 12 <212> PRT <213> Influenza A virus <400> 371

Gly Val Tht Asn Lys Val Asn Arg Ile Ile Asp Lys 15 10

<210> 372 <211 > 12 <212> PRT <213> Influenza A virus <400> 372

Gly Ile Thr Asn Lys Val Asn Ser Val Ile Glu Lys 15 10

<210> 373 <211 > 12 <212> PRT <213> Influenza A virus <400> 373

Gly Ile Thr Asn Lys Glu Asn Ser Val Ile Glu Lys 15 10

<210> 374 <211 > 12 <212> PRT <213> Influenza A virus <400> 374

Gly Ile Thr Asn Lys Val Asn Ser Ile Ile Asp Lys 15 10

<210> 375 <211 > 12 <212> PRT <213> Influenza A virus <400> 375

Lys Ile Thr Ser Lys Val Asn Asn Ile Val Asp Lys 15 10

<210> 376 <211 > 12 <212> PRT <213> Influenza A virus <400> 376

Gin Ile Asn Gly Lys Leu Asn Arg Val Ile Glu Lys 15 10

<210> 377 <211> 12 <212> PRT <213> Influenza A virus <400> 377

Gin Ile Asn Gly Lys Leu Asn Arg Leu Ile Glu Lys 1 5 10

REFERENCES CITED IN THE DESCRIPTION

This list of references cited by the applicant is for the reader's convenience only. It does not form part of the European patent document. Even though great care has been taken in compiling the references, errors or omissions cannot be excluded and the EPO disclaims all liability in this regard.

Patent documents cited in the description • WO20Q7045674A Γ0047Ι • W00063403A Γ00641 • WO8403564A rø0891 • WO9309872A F00891 • VV002103012A 100951 10096] [00931 [0098] • US62651503 100961 • WQ9815833A fOOSOl • EP2007059356W 101471 • US60842930B F01471 • ΕΡΟβ Ί 20316A f01471 • ΕΡΟβΙ 20644A 101471 • EP06125107A 101471 • EP07111235A Γ01471

Non-patent literature cited in the description • Antibodies: A Laboratory ManualCold Spring Harbor Laboratoryl 9880000 [0011] • WHO Manual on Animal Influenza Diagnosis and SurveillanceGeneva: World Health 0rganisation20050000 f00431 • KABAT et al.Sequences of Proteins of Immunological Interest, 1991, [0051] • TOMLINSON IMWILLIAMS SCIGNATOVITCH OCORBETT SJWINTER GV-BASE Sequence Directory. Cambridge United Kingdom: MRC Centre for Protein Engineering, 1997, [0052} • Using Antibodies: A Laboratory ManualCold Spring Harbor Laboratoryl9980000 [0037] • Current Protocols in ImmunologyJohn Wiley & Sons lnc.20010000 Γ00671 • TOMLINSON IM et al.V-BASE Sequence Directory. Cambridge United Kingdom: MRC Centre for Protein Engineering, 1997, 101021 • BOEL E et al.Functional human monoclonal antibodies of all isotypes constructed from phage display library-derived single-chain Fv antibody fragmentsJ. Immunol. Methods, 2000, vol. 239, 153-166 [0146] • BURTON DRBARBAS CFHuman antibodies from combinatorial librariesAdv. Immunol., 1994, vol. 57, 191-280 101461 • CHOU TCP TALALAY Quantitative analysis of dose-effect relationships: the combined effects of multiple drugs or enzyme inhibitorsAdv Enzyme Regul, 1984, vol. 22, 27-55 [0146] • DE KRUIF J et al.Rapid selection of cell subpopulation-specific human monoclonal antibodies from a synthetic phage antibody libraryProc Natl Acad Sci USA, 1995, vol. 92, 3938- [0146] • DE KRUIF J et al.Selection and application of human single-chain Fv antibody fragments from a semi-synthetic phage antibody display library with designed CDR3 regionsJ. Mol. Biol., 1995, vol. 248, 97-105 [0146] • HULS G et al.Antitumor immune effector mechanisms recruited by phage display-derived fully human lgG1 and lgA1 monoclonal antibodiesCancer Res, 1999, vol. 59, 5778-5784 [01461 • OKUNO Y et al.A common neutralizing epitope conserved between the hemagglutinins of Influenza A virus H1 and H2 strainsJ. Virol., 1993, vol. 67, 2552-2558 [01481 • SLOOTSTRA JW et al.Structural aspects of antibody-antigen interaction revealed through small random peptide librariesMol. Divers., 1996, vol. 1,87-96 [0146] • SMIRNOV YAet al.An epitope shared by the hemagglutinins of H1, H2, H5 and H6 subtypes of influenza A virusActa Virol., 1999, vol. 43, 237-244 [6146] • Evolution of H5N1 Avian Influenza Viruses in AsiaEmerg Infect Dis, 2005, vol. 11, 1515-1521 [01461

Claims

1. Humant monoklonalt antistof, eller antigenbindende fragment deraf, der er i stand til at genkende og binde til en epitop i HA2-subunitten af influenza-hæmagglutininproteinet (HA), der er kendetegnet ved, at antistoffet, eller det antigenbindende fragment, har neutraliserende aktivitet mod et influenzavirus, der omfatter HA af H5-undertypen, hvor antistoffet, eller det antigenbindende fragment, omfatter et CDRl-område af tung kæde ifølge SEQ ID NO: 39, et CDR2-område af tung kæde ifølge SEQ ID NO: 40 og et CDR3-område af tung kæde ifølge SEQ ID NO: 41 og et let CDRl-område ifølge SEQ ID NO: 42, et CDR2-område af let kæde ifølge SEQ ID NO: 43, og et CDR3-område af let kæde ifølge SEQ ID NO: 44.

2. Humant monoklonalt antistof eller et antigenbindende fragment deraf ifølge krav 1, hvor antistoffet eller det antigenbindende fragment også har neutraliserende aktivitet mod et influenzavirus, der omfatter HA af Hl-undertypen, såsom H1N1.

3. Humant monoklonalt antistof eller et antigenbindende fragment deraf ifølge krav 1 eller 2 til anvendelse som et medikament.

4. Humant monoklonalt antistof eller et antigenbindende fragment deraf ifølge krav 1 eller 2 til anvendelse til diagnosticering, profylakse og/eller behandling af influenzainfektion.

5. Humant monoklonalt antistof eller et antigenbindende fragment deraf til anvendelse ifølge krav 4, hvor influenzainfektionen forårsages af et influenzavirus, der er forbundet med et pandemisk udbrud eller har potentiale til at være forbundet med et pandemisk udbrud.

6. Humant monoklonalt antistof eller et antigenbindende fragment deraf eller til anvendelse ifølge krav 5, hvor influenzavirusstammen, der er forbundet med et pandemisk udbrud, er udvalgt fra gruppen, der består af: H1N1, H5N1, H5N2, H5N8, H5N9, en H2-baseret stamme og H9N2.

7. Nukleinsyremolekyle, der koder for et humant monoklonalt antistof eller et antigenbindende fragment deraf ifølge et hvilket som helst af kravene 1-6.

8. Farmaceutisk sammensætning, der omfatter et humant monoklonalt antistof eller et antigenbindende fragment deraf ifølge et hvilket som helst af kravene 1-6 og et farmaceutisk acceptabelt excipiens.