RU2810748C2 - Advanced procoagulant antibodies - Google Patents

Abstract

FIELD: biotechnology.

SUBSTANCE: following is proposed: bispecific antibodies capable of binding to blood coagulation factor IX (FIX) and/or its activated form (FIXa) and factor X (FX) and/or its activated form (FXa) and stimulating the activation of FX under the influence of FIXa. Also the following is proposed: an antibody or an antigen-binding fragment thereof that binds to FIX and/or its activated form (FIXa) and is an intermediate in the production of these bispecific antibodies. The invention also relates to a pharmaceutical composition and a kit for the treatment of coagulopathy or bleeding disorders, containing the specified bispecific antibodies.

EFFECT: invention provides improved stimulation of the enzymatic activity of FIXa in relation to FX.

19 cl, 9 dwg, 21 tbl, 17 ex

Description

Incorporating a sequence listing by reference

This application is submitted with a sequence listing in electronic form. The entire contents of the sequence listing are hereby incorporated herein by reference.

State of the art

In patients with coagulopathy, such as people with hemophilia A and B, the function of various steps of the coagulation cascade becomes impaired, for example due to the absence or insufficient presence of a functional clotting factor. This dysfunction of one part of the coagulation cascade leads to insufficient blood clotting and potentially life-threatening bleeding or damage to internal organs such as joints.

Blood clotting factor VIII (FVIII) deficiency, commonly referred to as hemophilia A, is a congenital bleeding disorder affecting approximately 420,000 people worldwide, of whom approximately 105,000 are currently diagnosed.

Patients with hemophilia A may receive clotting factor replacement therapy, such as exogenous FVIII. Traditional treatment consists of replacement therapy given as prophylaxis or as needed to treat bleeding episodes. Until recently, prophylactic treatment for a patient with severe hemophilia A was the administration of no more than three intravenous injections per week of either plasma-derived FVIII or recombinant FVIII, or long-acting variants thereof.

However, such patients are at risk of developing neutralizing antibodies, called inhibitors, to such exogenous factors, rendering previously effective therapy ineffective. Hemophilia A in patients with inhibitors is a non-limiting example of a coagulopathy that is partly congenital and partly acquired. Patients who develop FVIII inhibitors cannot be treated with traditional replacement therapy. Exogenous blood coagulation factors can only be administered intravenously, which creates significant inconvenience and discomfort for patients. For example, infants and young children may require intravenous catheters to be surgically inserted into a chest vein to ensure access to the vein. This puts them at great risk of developing bacterial infections.

In a bleeding individual, coagulation is initiated by the formation of the tissue factor/factor VIIa (TF/FVIIa) complex when extravascular TF is exposed to activated FVII (FVIIa) in the blood. Formation of the TF/FVIIa complex leads to the activation of factor X (FX) to activated factor Xa (FXa), which together with activated factor V (FVa) leads to the formation of a limited amount of thrombin, which in turn activates platelets in the blood. Activated platelets support the assembly of a tenase complex consisting of activated factor VIII (FVIIIa) and activated factor IX (FIXa). The tenase complex is a very efficient catalyst for FX activation, and the FXa produced in this second step serves as the active protease in the FVa/FXa prothrombinase complex, which is responsible for the final thrombin burst. Thrombin breaks down fibrinogen to form fibrin monomers, which polymerize to form a fibrin network that seals the leaking vessel and stops bleeding. A rapid and extensive thrombin burst is a prerequisite for the formation of a solid and stable fibrin clot.

Insufficient production of FXa and decreased thrombin production caused by decreased or absent FVIII activity is the underlying cause of bleeding diathesis in patients with hemophilia A.

As mentioned, the proteolytic conversion of FX to its enzymatically active form FXa can be achieved using a proprietary FX activating complex containing FIXa and its cofactor FVIIIa. Cofactor binding increases the enzymatic activity of FIXa by approximately five orders of magnitude and is believed to occur through several mechanisms described by Scheiflinger et al. (2008) J Thromb Haemost 6:315–322. Of note, FVIIIa has been found to stabilize the conformation of FIXa, which has increased proteolytic activity towards FX (Kolkman JA, Mertens K (2000) Biochemistry, 39:7398–7405, Zögg T, Brandstetter H (2009) Biol Chem, 390: 391–400). Based on this observation and recognizing that antibodies are versatile binding proteins capable of mimicking a variety of protein-protein interactions, Scheiflinger et al. screened for agonistic antibodies to FIXa, characterized by the ability to enhance FX activation by FIXa in the presence of a phospholipid surface and calcium, but in the absence of the natural cofactor FVIIIa. As a result of screening supernatants from 5280 hybridomas, 88 were found that produce antibodies exhibiting varying degrees of agonistic activity against FIXa, see EP1220923 B1 and EP1660536 B1. In terms of FX activation kinetics and ability to stimulate thrombin generation in FVIII-deficient human plasma, EP1660536 B1 consistently points to anti-FIXa antibody 224F3 as the most effective antibody.

Recently, a new drug emicizumab (HEMLIBRA^®), also known as ACE910, has been approved for the subcutaneous prophylactic treatment of hemophilia A with or without inhibitors against conventional replacement therapy factors. Emicizumab is a humanized bispecific monoclonal antibody to FIX(a)/FX(a) developed by Chugai Pharmaceuticals/Roche Pharmaceuticals for the treatment of hemophilia A. Emicizumab mimics the function of the FVIII cofactor (see Sampei et al.: (2013) PLoS One, 8, e57479 and WO2012067176), however, some patients developed inhibitors against emicizumab, rendering treatment with this compound ineffective.

There are still many unmet medical needs in the group of individuals with hemophilia in particular, and in subjects with types of coagulopathy in general, and the present invention relates to improved compounds capable of replacing FVIII and thus useful for the treatment of coagulopathy such as hemophilia A.

Brief description of the invention

The present invention relates to compounds that serve as a replacement for coagulation factor VIII (FVIII) in patients suffering from coagulopathy, and in particular in patients who lack functional FVIII, such as patients with hemophilia A, including patients with hemophilia A with the presence of inhibitors.

Therefore, one aspect of the present invention relates to compounds capable of enhancing the production of FXa and thereby partially or completely restoring coagulation in patients who lack functional FVIII.

In one aspect, the compound is an antibody or an antigen-binding fragment thereof. In one such aspect, the compound is a multispecific antibody or antigen binding fragment thereof, such as a bispecific antibody or antigen binding fragment thereof.

In one particular aspect, the present invention provides procoagulant antibodies or antigen binding fragments thereof that serve as a replacement for FVIII in patients who lack functional FVIII, such as patients with hemophilia A.

In one such aspect, the antibody or antigen binding fragment thereof is capable of binding FIX(a) and increasing the enzymatic activity of FIXa towards FX, without necessarily also being able to bind FX.

In one aspect, the present invention provides a procoagulant antibody or antigen binding fragment thereof that is capable of binding FIX(a) and FX(a), including bispecific procoagulant antibodies or antigen binding fragments thereof that enhance the enzymatic activity of FIXa against FX.

In one aspect, the present invention provides a procoagulant bispecific antibody or antigen binding fragment thereof that is capable of binding to FIX(a) and FX(a).

A further aspect of the present invention relates to individual component antibodies (intermediates) or antigen binding fragments thereof that are part of a procoagulant antibody, such as a particular anti-FIX(a) antibody or antigen binding fragment thereof or a particular anti-FX(a) antibody or antigen binding fragment thereof.

An additional aspect of the present invention relates to the manufacture of antibodies or antigen-binding fragments thereof and their components (intermediates) disclosed herein.

An additional aspect of the present invention provides an antibody that competes with a procoagulant antibody or antigen binding fragment thereof disclosed herein for binding to FIX(a) and/or FX(a).

An additional aspect of the present invention relates to an antibody or antigen binding fragment thereof that shares epitope residues or epitope hot spot residues on FIX(a) and/or FX(a) with the procoagulant antibody or antigen binding fragment thereof disclosed herein.

An additional aspect of the present invention is directed to procoagulant antibodies or antigen binding fragments thereof disclosed herein for the prevention and/or treatment of coagulopathy, a disease accompanying a coagulopathy, or a disease caused by a coagulopathy. In one aspect, the coagulopathy is hemophilia A with or without the presence of inhibitors.

Another further aspect of the present invention relates to a pharmaceutical composition containing a procoagulant antibody or antigen binding fragment thereof disclosed herein, formulated to deliver said antibody for the prevention and/or treatment of a coagulopathy such as hemophilia A with or without the presence of inhibitors, and to the injection device and its contents.

An additional aspect of the present invention is directed to a kit containing (i) an antibody or antigen binding fragment thereof disclosed herein, such as a bispecific antibody, and (ii) instructions for use.

The present invention may also provide solutions to additional objects that will be apparent from the disclosure of the illustrative embodiments.

Brief description of graphic materials

Figure 1A-D shows a sequence alignment representing the variable domains of the heavy and light chains of the anti-FIX(a) (FIGS. 1A and 1B) and anti-FX(a) (FIGS. 1C and 1D) IgG antibodies disclosed herein. The CDR1, 2 and 3 sequences are in bold and underlined in the topmost sequence and are characteristic of the remaining sequences.

Figure 2 shows the results of the thrombin generation test (TGT) for bispecific antibodies bimAb05-0745, bimAb05-3761, bimAb05-3769, bimAb05-0746, bimAb05-2112, bimAb05-2113, bimAb05-2114 and ACE910 in tissue factor-activated platelet-depleted platelets. blood plasma person with hemophilia A (PPP). The experiment was performed as described in Example 16. The dotted and dashed lines indicate the peak level (nM) of thrombin observed in the absence of antibody in HA-PPP and normal PPP, respectively, and their standard deviation, indicated by the dotted lines. The bimAb05-0745, bimAb05-3761, bimAb05-3769, bimAb05-0746, bimAb05-2112, bimAb05-2113 and bimAb05-2114 profiles are indicated by downward-pointing triangles, while the ACE910 profile is indicated by upward-pointing triangles. Results are presented as mean ± standard deviation based on at least three independent experiments.

Figure 3 shows the results of the thrombin generation test (TGT) for bispecific antibodies bimAb05-0745, bimAb05-3761, bimAb05-3769, bimAb05-0746, bimAb05-2112, bimAb05-2113, bimAb05-2114 and ACE910 in tissue factor-activated platelet-rich platelet. blood plasma person with hemophilia A (PRP). The experiment was performed as described in Example 16. The dotted and dashed lines indicate the peak level (nM) of thrombin observed in the absence of antibody in HA-PRP and normal PRP, respectively, and their standard deviation, indicated by the dotted lines. The bimAb05-0745, bimAb05-3761, bimAb05-3769, bimAb05-0746, bimAb05-2112, bimAb05-2113 and bimAb05-2114 profiles are indicated by downward-pointing triangles, while the ACE910 profile is indicated by upward-pointing triangles. Results are presented as mean ± standard deviation based on at least three independent experiments.

Figures 4A and 4B show the results of antibody sorting experiments on the Octet Fortebio system using a modified tandem mode. Briefly, biotinylated human FIXa was captured on streptavidin tips. The captured FIXa was then saturated with an initial exposure to the first (1st) bivalent anti-FIXa antibody, followed by a second exposure to an equimolar mixture of the first (1st) antibody and the second (2nd) bivalent anti-FIXa antibody. The binding responses for each of the three phases are shown, along with the designation of the antibodies used.

Figure 5 shows the results of experiments on sorting antibodies into groups in the Octet Fortebio system using a modified tandem mode. Briefly, biotinylated human FXa was captured on streptavidin tips. Captured FXa was then saturated by an initial exposure to the first (1st) bivalent anti-FXa antibody, followed by a second exposure to an equimolar mixture of the first (1st) antibody and the second (2nd) bivalent anti-FXa antibody. The binding responses for each of the three phases are shown, along with the designation of the antibodies used.

Brief description of sequences

SEQ ID NO:1 represents the amino acid sequence of human coagulation factor IX.

SEQ ID NO:2 represents the amino acid sequence of human blood coagulation factor X.

SEQ ID NOs: 3-1194 and 1202-1249 represent the sequences of the heavy chain variable domains (VH), light chain variable domains (VL) and complementarity determining regions (CDRs) of monoclonal antibodies (mAbs) to FIX(a) and FX(a ) described in this document.

SEQ ID NO:1195 represents the human IgG4 heavy chain constant region with S228P and a C-terminal lysine truncation.

SEQ ID NO:1196 represents the human IgG4 heavy chain constant region with S228P, F405L, R409K and a C-terminal lysine truncation.

SEQ ID NO:1197 represents the human kappa light chain constant region.

SEQ ID NO:1198 represents the human IgG1 heavy chain constant region with F405L and a C-terminal lysine truncation.

SEQ ID NO:1199 represents the human IgG1 heavy chain constant region with K405R and a C-terminal lysine truncation.

SEQ ID NO:1200 represents the N-terminal His tag.

SEQ ID NO:1201 represents the GS linker.

The tables in Example 6 associate SEQ ID NOs with the individual anti-FIX(a) and anti-FX(a) antibodies and bispecific antibodies of the present invention.

DESCRIPTION

In subjects with coagulopathy, such as people with hemophilia A, the function of the coagulation cascade becomes impaired due to the absence or insufficient presence of functional FVIII. This dysfunction of one part of the coagulation cascade leads to insufficient blood clotting and potentially life-threatening bleeding or damage to internal organs such as joints. The present invention relates to compounds that serve as a replacement for coagulation factor VIII (FVIII) in patients suffering from coagulopathy, and in particular in patients who lack functional FVIII, such as patients with hemophilia A, including patients with hemophilia A with the presence of inhibitors. In one aspect, such a compound is an antibody.

In particular, the inventors of the present invention have unexpectedly identified antibodies that mimic the activity of the FVIII cofactor with high potency and potency. In one particular aspect, the present invention provides procoagulant antibodies that serve as a replacement for FVIII in patients who lack functional FVIII, such as patients with hemophilia A. In one such aspect, the procoagulant antibodies bind to coagulation factor IXa (FIXa) and increase its enzymatic activity against coagulation factor X (FX), optionally also binding to FX. In one such aspect, the antibodies of the present invention are bispecific antibodies capable of binding to FIX/FIXa and FX.

An additional aspect of the present invention relates to individual component antibodies (intermediates) or antigen binding fragments thereof that are part of a multispecific procoagulant antibody, such as a specific anti-FIX(a) antibody or antigen binding fragment thereof or a specific anti-FX(a) antibody or antigen binding fragment thereof .

An additional aspect of the present invention relates to the manufacture of antibodies or antigen-binding fragments thereof and their components (intermediates) disclosed herein.

An additional aspect of the present invention provides an antibody that competes with a procoagulant antibody or antigen binding fragment thereof disclosed herein for binding to FIX(a) and/or FX(a).

An additional aspect of the present invention relates to an antibody or antigen binding fragment thereof that shares epitope residues or epitope hot spot residues on FIX(a) and/or FX(a) with the procoagulant antibody or antigen binding fragment thereof disclosed herein.

In one aspect, the antibody is a human or humanized antibody, such as a human or humanized bispecific antibody.

An additional aspect of the present invention is directed to procoagulant antibodies or antigen binding fragments thereof disclosed herein for the prevention and/or treatment of coagulopathy, a disease accompanying a coagulopathy, or a disease caused by a coagulopathy. In one aspect, the coagulopathy is hemophilia A with or without the presence of inhibitors.

Another further aspect of the present invention relates to a pharmaceutical composition containing a procoagulant antibody or antigen binding fragment thereof disclosed herein, formulated to deliver said antibody for the prevention and/or treatment of a coagulopathy such as hemophilia A with or without the presence of inhibitors, and to the injection device and its contents.

An additional aspect of the present invention is directed to a kit containing (i) an antibody or antigen binding fragment thereof disclosed herein, such as a bispecific antibody, and (ii) instructions for use.

Clotting factor IX

Factor IX (FIX) is a vitamin K-dependent coagulation factor with structural similarities to factor VII, prothrombin, factor X, and C protein. FIX circulates in plasma as a single-chain zymogen (SEQ ID NO:1). The circulating zymogenic form consists of 415 amino acids divided into four distinct domains, including an N-terminal γ-carboxyglutamic acid (Gla)-rich domain, two EGF domains, and a C-terminal trypsin-like serine protease domain. Activation of FIX occurs through limited proteolysis at Arg145 and Arg180, releasing the activation peptide (residues 146-180 of SEQ ID NO:1). Thus, activated FIX (FIXa) consists of residues 1-145 of SEQ ID NO:1 (light chain) and residues 181-415 of SEQ ID NO:1 (heavy chain).

Thus, circulating FIX molecules include the FIX zymogen and the activated form of FIX, which are collectively referred to herein as FIX and FIXa with reference to SEQ ID NO:1.

Activated factor IX is designated factor IXa or FIXa. The term "FIX (SEQ ID NO:1) and/or its activated form (FIXa)" may also be referred to as "FIX/FIXa" or simply "FIX(a)".

FIXa is a trypsin-like serine protease that plays a key role in hemostasis; as part of the tenase complex, it forms most of the factor Xa required to maintain proper thrombin generation during coagulation.

FIX is presented herein under SEQ ID NO:1, which corresponds to the Ala148 allelic form of human FIX (Anson et al. EMBO J. 1984 3:1053–1060; McGraw et al., Proc Natl Acad Sci USA. 1985 82:2847– 2851; Graham et al Am J Hum Genet 1988 42:573–580). In the present invention, FIX is intended to cover all naturally occurring FIX variants, such as the T148 variant (Uniprot ID P00740).

Clotting factor X

FX is a vitamin K-dependent coagulation factor with structural similarities to factor VII, prothrombin, FIX, and C protein. FX circulates in the blood plasma as a double-chain zymogen comprising residues 1-139 of SEQ ID NO:2 (light chain) and residues 143-448 of SEQ ID NO:2 (heavy chain). The human FX zymogen contains four distinct domains containing an N-terminal gamma-carboxyglutamic acid (Gla)-rich domain (residues 1–45), two EGF domains, EGF1 (residues 46–82) and EGF2 (residues 85–125), respectively, and a C-terminal domain that is a trypsin-like serine protease (residues 195–448). Activation of FX occurs through limited proteolysis at Arg194, resulting in the release of the activation peptide (residues 143–194). Thus, activated FX (FXa) consists of residues 1-139 of SEQ ID NO:2 (light chain) and residues 195-448 of SEQ ID NO:2 (activated heavy chain). Thus, circulating factor X molecules include the zymogen FX and the activated form of FX, which are herein referred to as FX and FXa, respectively, with reference to SEQ ID NO:2. In the present invention, FX is intended to include all naturally occurring FX variants. The term "FX (SEQ ID NO:2) and/or its activated form (FXa)" may also be referred to as "FX/FXa" or "FX(a)".

Antibodies

The term “antibody” as used herein refers to a protein derived from an immunoglobulin sequence that is capable of binding to an antigen or part thereof. The term antibody includes, without limitation, full-length antibodies of any class (or isotype), i.e., IgA, IgD, IgE, IgG, IgM and/or IgY. The term antibody includes, without limitation, antibodies that are bivalent, such as bispecific antibodies.

Natural full-length antibodies contain at least four polypeptide chains: two heavy chains (HC) and two light chains (LC), which are linked by disulfide bonds. In some cases, natural antibodies contain fewer than four chains, as is the case with IgNARs found in Chondrichthyes. One class of immunoglobulins, IgG, is of particular interest for the production of pharmaceuticals. In humans, the IgG class can be divided into four subclasses IgG1, IgG2, IgG3 and IgG4 based on the sequence of their heavy chain constant regions. Light chains can be divided into two types: kappa and lambda chains, based on differences in their sequence composition. IgG molecules consist of two heavy chains linked by two or more disulfide bonds and two light chains, each attached to the heavy chain by a disulfide bond. An IgG heavy chain may contain a heavy chain variable domain ( _VH ) and up to three heavy chain constant domains ( _CH ): _CH1 , _CH2 and _CH3 . A light chain may contain a light chain variable domain (VL ₎ and a light chain constant domain ( _CL ). The V _H and V _L regions can be further subdivided into regions of hypervariability called complementarity determining regions (CDRs) or hypervariable regions (HvRs), interspersed with more conserved regions called framework regions (FRs). The V _H and V _L domains typically consist of three CDRs and four FRs, arranged from amino terminus to carboxy terminus in the following order: FR1, CDR1, FR2, CDR2, FR3, CDR3, FR4. The variable domains of the heavy and light chains, containing hypervariable regions (CDRs), form a structure that is capable of interacting with the antigen, while the constant region of the antibody can mediate binding of the immunoglobulin to host tissues or factors, including, but not limited to, various cells immune system (effector cells), Fc receptors and the first component, C1q, from the C1 complex of the classical complement system.

The antibodies of the present invention may be monoclonal antibodies (mAbs) in the sense that they are a set of unique heavy and light chain variable domain sequences expressed by a single B cell or clonal population of B cells. Antibodies of the present invention can be prepared and purified using various methods known to one skilled in the art. For example, antibodies can be obtained from hybridoma cells. Antibodies can be produced by expanding B cells. Antibodies or fragments thereof can be recombinantly expressed in mammalian or microbial cell-based expression systems or by in vitro translation. Antibodies or fragments thereof can also be recombinantly expressed as molecules associated with the cell surface, for example, using phage display, bacterial display, yeast display, mammalian cell display, or ribosomal or mRNA display.

Antibodies of the present invention can be isolated. The term "isolated antibody" refers to an antibody that has been separated from and/or extracted from other component(s) in the environment in which it was produced and/or which has been purified from a mixture of components present in the environment in which it was produced.

Certain antigen-binding antibody fragments may be suitable in the context of the present invention, since it has been shown that the antigen-binding function of an antibody can be performed by fragments of a full-length antibody. The term "antigen binding fragment" of an antibody refers to one or more antibody fragments that retain the ability to specifically bind to or recognize an antigen, such as FIX/FIXa, FX/FXa or other target molecule described herein. Examples of antigen binding fragments include, but are not limited to, Fab, Fab', Fab ₂ , Fab' ₂ , Fv (typically a combination of the V _L and V _H domains from one arm of the antibody), single chain Fv (scFv); see, for example, Bird et al. Science 1988; 242:423–426 and Huston et al. PNAS 1988; 85:5879–5883), dsFv, Fd (usually a _VH and _CH1 domain), monovalent molecules containing both one _VH and one _VL domain; minibodies, diabodies, tribodies, tetrabodies and kappa bodies (see, for example, Ill et al (1997) Protein Eng 10: 949–57); and one or more isolated CDRs or functional paratope, wherein the isolated CDRs or antigen-binding residues or polypeptides can be associated or linked together to form a functional antibody fragment. These antibody fragments can be prepared using conventional techniques known to those skilled in the art, and the fragments can be screened for their utility in the same manner as intact antibodies.

Antibody "Fab" fragments, including "Fab" and "Fab' ₂ " fragments, can be produced from an antibody by heavy chain cleavage at the hinge region at the N-terminal or C-terminal side, respectively, of the hinge cysteine residues connecting the antibody heavy chains . The "Fab" fragment includes a light chain variable and constant domain and a heavy chain variable and C _H 1 domain. "Fab' ₂ " fragments contain a pair of "Fab'" fragments that are usually covalently linked by their hinge cysteine residues. Fab' is typically prepared from the Fab' ₂ fragment by cleavage of the hinge disulfide bonds connecting the heavy chains in Fab' ₂ . Other chemical bonds of antibody fragments other than disulfide bonds are also known from the prior art. The Fab fragment retains the ability of the parent antibody to bind to its antigen, potentially with lower affinity. Fab' ₂ fragments are capable of bivalent binding, whereas Fab and Fab' fragments can only bind monovalently. Typically, Fab fragments lack constant domains C _H 2 and C _H 3, i.e. Fc part, where interaction with Fc receptors and C1q could occur. Thus, Fab fragments generally lack effector functions. Fab fragments can be prepared using methods known in the art or by enzymatic digestion of the antibody, for example using papain to produce Fab or pepsin to produce Fab' ₂ , or Fab fragments including Fab, Fab', Fab' ₂ can be produced recombinantly using techniques that are well known to one skilled in the art.

An "Fv" fragment (variable fragment) is an antibody fragment that contains a complete antigen recognition and binding site and typically contains one heavy chain variable domain and one light chain variable domain in an association that may be covalent in nature, e.g. variable domain fragment (scFv). It is in this configuration that the three hypervariable regions of each variable domain interact to form an antigen binding site on the surface of the V _H -V _L dimer. Collectively, the six hypervariable regions or a subset thereof provide the antibody with antigen binding specificity.

A "single chain Fv" or "scFv" antibody contains the V _H and V _L domains of the antibody, where these domains are present on the same polypeptide chain. Typically, the Fv polypeptide further contains a polypeptide linker between the V _H and V _L domains, which allows the scFv to form the structure necessary for antigen binding. For a review of scFv, see Pluckthun, 1994, in: The Pharmacology of Monoclonal Antibodies, Vol. 113, Rosenburg and Moore eds. Springer-Verlag, New York, pp. 269–315.

A "single chain Fab" or "scFab" antibody contains the _VH , _CH1 , _VL and _CL domains of the antibody, where these domains are present on a single polypeptide chain. Typically, the Fab polypeptide additionally contains a polypeptide linker between the V _H and C _L or V _L and C _H 1 domains, which allows the scFab to form the structure necessary for antigen binding (Koerber et al. (2015) J Mol Biol. 427:576–86) .

The term "diabodies" refers to small antibody fragments with two antigen-binding regions, the fragments containing a heavy chain variable domain ( _VH ) joined to a light chain variable domain ( _VL ) in the same polypeptide chain ( _VH and _VL ) . When using a linker that is too short to allow pairing between two variable domains on the same chain, the variable domains are forced to pair with complementary domains on the other chain, creating two antigen binding sites.

The expression "linear antibodies" refers to the antibodies described in Zapata et al. (1995) Protein Eng. 8:1057–1062. Briefly, these antibodies contain a pair of tandem Fd segments (V _H -C _H 1-V _H -C _H 1), which together with complementary light chain polypeptides form a pair of antigen binding regions. Linear antibodies can be bispecific or monospecific.

Antibody fragments can be produced using conventional recombinant or protein engineering techniques, and the fragments can be screened for binding to FIX and its activated form, FX or other functional element in the same manner as intact antibodies.

Antibody fragments of the present invention can be produced by truncation, for example, by removing one or more amino acids from the N- and/or C-termini of the polypeptide. Fragments can also be generated by one or more internal deletions.

An antibody of the present invention may be or may contain an antibody fragment or variant of any of the antibodies disclosed herein. An antibody of the present invention may be or may contain an antigen-binding portion of one of these antibodies or variants thereof. For example, an antibody of the present invention may be a Fab fragment of one of these antibodies or variants thereof, or it may be a single chain antibody derived from one of these antibodies or a variant thereof. Also, the antibody of the present invention may be a combination of a full-length antibody and a fragment thereof.

As used herein, the term “single-arm” refers to a specific type of monovalent antibody consisting of an antibody heavy chain, a truncated heavy chain lacking the Fab region, and a single light chain.

As used herein, the term “monospecific” antibody refers to an antibody that is capable of binding to one specific epitope (including, without limitation, bivalent antibodies).

As used herein, the term “bispecific” antibody refers to an antibody that is capable of binding to two different antigens or two different epitopes on the same antigen.

As used herein, the term “trispecific” antibody refers to an antibody that is capable of binding to three different antigens, or three different epitopes on the same antigen, or three different epitopes present on two different antigens.

As used herein, the term “multispecific” antibody refers to an antibody that is capable of binding to two or more different antigens or two or more different epitopes on the same antigen. Thus, multispecific antibodies include bi- and trispecific antibodies.

Bispecific antibodies in full-length IgG format can be produced by fusing two separate hybridomas to form a hybrid quadromy, which produces an antibody mixture that includes a fraction of bispecific heterodimerizing antibodies (Chelius D. et al.; MAbs. 2010 May-Jun; 2(3): 309 –319). Bispecific heterodimerizing antibodies can alternatively be produced using recombinant techniques. Heterodimerization can also be achieved by designing a dimerization interface in the Fc region to promote heterodimerization. One example of this is the so-called "knob-to-groove" mutations, where sterically bulky side chains (knobs) are introduced into one Fc that matches sterically small side chains (grooves) on the opposite Fc, thereby creating steric complementarity that promotes heterodimerization. Other ways to design interfaces on the Fc for heterodimerization are electrostatic complementarity, fusion with non-IgG heterodimerization domains, or using the natural phenomenon of Fab arm exchange in human IgG4 to drive heterodimerization. Examples of heterodimerized bispecific antibodies are well described in the literature, for example (Klein C, et al.; MAbs. 2012 Nov-Dec; 4(6): 653–663). Particular attention should be paid to the light chains in heterodimeric antibodies. Correct pairing of LC and HC can be achieved by using a common light chain. Again, engineering of the LC/HC interface can be used to promote heterodimerization or engineering of light chain crossover, as in CrossMabs. Reassembly of antibodies in vitro under slightly reducing conditions from two separate IgGs containing the appropriate mutations can also be used to produce bispecific antibodies (e.g., Labrijn et al., PNAS, 110, 5145–5150 (2013)). It is also reported that nature's Fab arm exchange method ensures proper light chain pairing.

Multispecific antibody molecules can also be expressed recombinantly as fusion proteins that combine natural IgG modules to form multispecific and multivalent antibody derivatives described in the literature. Examples of fusion antibodies are DVD-Ig, IgG-scFV, diabodies, DART, etc. Fusion proteins can be incorporated with specific tags for detection or purification, fragments to extend half-life, or other components. Additional non-IgG elements can also be introduced into the fusion proteins. Bispecific full-length antibodies based on Fc heterodimerization are generally referred to as asymmetric IgG, regardless of LC pairing methodology.

Typically, bispecific antibodies can be produced in various molecular formats, as described by Brinkmann et al. (Brinkmann et al. The making of bispecific antibodies. Mabs 9, 182–212 (2017)).

Multispecific antibody molecules can also be produced by chemical conjugation or conjugation of individual full-length IgGs or conjugation of IgG fragments to form multispecific and multivalent antibody derivatives described in the literature. Examples are chemically conjugated Fab fragments, an IgG dimer, etc. Conjugated proteins can be incorporated with specific tags for detection or purification, molecules to extend half-life, or other components. Additional non-IgG polypeptides can also be incorporated into the fusion proteins. Polyspecific molecules can also be produced by combining recombinant and chemical methods, including those described above.

In one aspect, the antibody of the present invention is a chimeric antibody, a human antibody, or a humanized antibody. Such an antibody can be produced using, for example, suitable antibody display or immunization platforms or other suitable platforms or methods known in the art. The term “human antibody” as used herein is intended to mean antibodies having variable domains in which at least a portion of the framework region and/or at least a portion of the CDR region are derived from human germline immunoglobulin sequences. For example, a human antibody may have variable domains in which both framework and CDR regions are derived from human germline immunoglobulin sequences. In addition, if the antibody contains a constant region, then the constant region or part thereof is also derived from human germline immunoglobulin sequences. The human antibodies of the present invention may include amino acid residues not encoded by human germline immunoglobulin sequences (eg, mutations introduced by random or site-specific mutagenesis in vitro or by somatic mutation in vivo).

Such a human antibody may be a human monoclonal antibody. Such a human monoclonal antibody may be produced by a hybridoma that comprises a B cell derived from a transgenic non-human animal, for example a transgenic mouse, having a genome comprising human immunoglobulin heavy and light chain gene segment repertoires fused to an immortalized cell.

Human antibodies can be isolated from sequence libraries built from sets of human germline sequences, further diversified by introducing natural and synthetic sequence diversity.

Human antibodies can be produced by immunizing human lymphocytes in vitro followed by transformation of the lymphocytes with the Epstein-Barr virus.

Human antibodies can be produced by recombinant methods known in the art.

The term “human antibody derivative” refers to any modified form of a human antibody, such as a conjugate of an antibody and another agent or antibody.

As used herein, the term “humanized antibody” refers to a human/non-human antibody that contains a sequence (CDR regions or portions thereof) derived from a non-human immunoglobulin. Thus, a humanized antibody is a human immunoglobulin (recipient antibody) in which residues from at least the hypervariable region of the recipient antibody are replaced by residues from the hypervariable region of an antibody from a non-human species (donor antibody), such as mouse, rat, rabbit, or other from a human primate that has the required sequence specificity, affinity, composition and functionality. In some cases, framework (FR) residues of human immunoglobulin are replaced with corresponding non-human residues. An example of such a modification is the introduction of one or more so-called reverse mutations, which are typically amino acid residues derived from the donor antibody. Humanization of an antibody can be accomplished using recombinant techniques known to one skilled in the art (see, for example, Antibody Engineering, Methods in Molecular Biology, vol. 248, edited by Benny K. Lo). Suitable human recipient frameworks for both light and heavy chain variable domains can be identified, for example, by sequence or structure homology. Alternatively, fixed recipient scaffolds can be used, for example based on knowledge of the structure, biophysical and biochemical properties. Recipient scaffolds can be derived from the germ line or derived from the mature antibody sequence. CDR regions from a donor antibody can be transferred by CDR grafting. The CDR-grafted humanized antibody can be further optimized, for example, with respect to affinity, functionality and biophysical properties, by identifying critical positions in the framework where reintroduction (back mutation) of an amino acid residue from the donor antibody has a beneficial effect on the properties of the humanized antibody. In addition to back mutations based on donor antibodies, a humanized antibody can be constructed by introducing germline residues into CDRs or framework regions, removing immunogenic epitopes, site-directed mutagenesis, affinity maturation, etc.

Moreover, humanized antibodies may contain residues that are not found in either the recipient antibody or the donor antibody. These modifications are made to further improve the performance characteristics of the antibody. In general, a humanized antibody will contain at least one, typically two, variable domains in which all or substantially all of the CDR regions correspond to regions of a non-human immunoglobulin, and in which all or substantially all of the FR residues are residues from an immunoglobulin sequence person. The humanized antibody may also optionally comprise at least a portion of the constant region (Fc) of an immunoglobulin, typically human immunoglobulin.

The term “humanized antibody derivative” refers to any modified form of a humanized antibody, such as an antibody-chemical conjugate or an antibody-another antibody conjugate.

As used herein, the term “chimeric antibody” refers to an antibody containing antibody portions derived from two or more species. For example, the genes encoding such an antibody include genes encoding variable domains and genes encoding constant domains originating from two different species. For example, genes encoding the variable domains of a murine monoclonal antibody can be linked to genes encoding the constant domains of a human-derived antibody.

The crystallizable fragment region ("Fc region"/"Fc domain") of an antibody is the C-terminal region of the antibody, which contains the hinge and constant domains C _H 2 and C _H 3. The Fc domain can interact with cell surface receptors called Fc- receptors, as well as with some proteins of the complement system. The Fc region allows antibodies to interact with the immune system. In one aspect of the present invention, antibodies can be engineered to include modifications within the Fc region, typically to alter one or more of its functional properties, such as serum half-life, complement fixation, Fc receptor binding, protein stability, and/or or antigen-dependent cellular cytotoxicity or lack thereof, among others. In addition, the antibody of the present invention can be chemically modified (eg, one or more chemical moieties can be attached to the antibody) or modified to alter its glycosylation, again to alter one or more functional properties of the antibody. An IgG1 antibody may carry a modified Fc domain containing one or more, and possibly all, of the following mutations, which will result in decreased affinity for certain Fc gamma receptors (L234A, L235E, and G237A) and decreased C1q-mediated complement fixation (A330S and P331S) respectively (numbering of residues in accordance with the EU index). Alternatively, other amino acid substitutions and combinations thereof and combinations thereof known in the art may be used to obtain altered (decreased or increased) binding to the Fc gamma receptor.

The antibody isotype of the present invention may be IgG, such as IgG1, such as IgG2, such as IgG4. If necessary, the antibody class can be “switched” using known techniques. For example, an antibody that was originally produced as an IgM molecule can be reclassified to an IgG antibody. Class switching techniques can also be used to convert one IgG subclass to another, for example from IgG1 to IgG2 or IgG4; from IgG2 to IgG1 or IgG4; or from IgG4 to IgG1 or IgG2. It is also possible to design antibodies to produce constant region chimeric molecules by combining regions from different IgG subclasses.

In one embodiment, the hinge region of the antibody is modified such that the number of cysteine residues in the hinge region is changed, such as increased or decreased. This approach is further described, for example, in US patent No. 5677425 from Bodmer et al.

The constant region can be modified to stabilize the antibody, for example to reduce the risk of the bivalent antibody separating into semi-antibodies. For example, in the lgG4 constant region, residue S228 (according to the EU numbering index and S241 according to Kabat) can be mutated to a proline residue (P) to stabilize the formation of a disulfide bridge between the heavy chains in the hinge (see, for example, Angal et al. Mol Immunol 1993;30:105–8).

Antibodies or fragments thereof can be defined in terms of their complementarity determining regions (CDRs). As used herein, the term “complementarity determining region” or “hypervariable region” refers to regions of an antibody that contain amino acid residues involved in antigen binding. The hypervariability region or CDR can be identified as the regions with the highest variability in the amino acid alignment of antibody variable domains. Databases such as the Kabat database can be used to identify CDRs, with CDRs, for example, being defined as containing amino acid residues 24-34 (L1), 50-56 (L2) and 89-97 (L3) of the light chain variable domain and 31–35 (H1), 50–65 (H2) and 95–102 (H3) in the heavy chain variable domain (Kabat et al. 1991; Sequences of Proteins of Immunological Interest, Fifth Edition, U.S. Department of Health and Human Services, NIH Publication No. 91–3242). Alternatively, CDRs can be defined as residues from the "hypervariable loop" (residues 26–33 (L1), 50–52 (L2) and 91–96 (L3) in the light chain variable domain and 26–32 (H1), 53– 55 (H2) and 96–101 (H3) in the heavy chain variable domain; Chothia and Lesk, J. Mol. Biol. 1987;196:901–917). Typically, numbering of amino acid residues in this region is performed using the method described in Kabat et al. higher. As used herein, phrases such as “Kabat position,” “Kabat residue,” and “Kabat residue” refer to this numbering system for heavy chain variable domains or light chain variable domains. When using the Kabat numbering system, the actual linear amino acid sequence of the peptide may contain fewer or additional amino acids corresponding to the truncation or insertion into the framework (FR) or CDR of the variable domain. For example, the heavy chain variable domain may include amino acid insertions (residues 52a, 52b and 52c according to Kabat) after residue 52 of CDR H2 and inserted residues (e.g. residues 82a, 82b and 82c, etc. according to Kabat) after residue 82 in the heavy chain FR. Kabat residue numbering can be determined for a given antibody by aligning regions of homology between the antibody sequence and the Kabat numbered “standard” sequence.

The term “framework region” or “FR” residues refers to those amino acid residues in V _H or V _L that are not within the CDRs defined herein.

An antibody of the present invention may comprise a CDR region from one or more of the specific antibodies disclosed herein.

The term "procoagulant antibody" refers to an antibody that enhances blood clotting, for example, by accelerating the blood clotting process and/or increasing the enzymatic activity of one or more clotting factors.

The term “procoagulant activity” refers to the ability of a compound, such as an antibody, to enhance blood clotting, for example, by accelerating the blood clotting process and/or increasing the enzymatic activity of one or more coagulation factors.

The term "antigen" (Ag) refers to a molecular entity used to immunize an immunocompetent vertebrate animal to produce an antibody (Ab) that recognizes the Ag. As used herein, Ag is defined more broadly and is generally understood to include target molecules that are specifically recognized by an Ab, thus including fragments or mimics of a molecule used in the immunization process or other process, such as phage display, used to produce the Ab.

The present invention covers variants of antibodies or antigen-binding fragments thereof of the present invention, which may contain 1, 2, 3, 4 or 5 amino acid substitutions and/or deletions and/or insertions in individual sequences disclosed herein.

"Substitution" variants preferably involve replacing one or more amino acids with the same number of amino acids. Unlimited substitutions may be conservative substitutions. For example, an amino acid can be replaced with an amino acid with similar biochemical properties, for example, a basic amino acid can be replaced with another basic amino acid (for example, lysine arginine), an acidic amino acid can be replaced with another acidic amino acid (for example, glutamate aspartate), a neutral amino acid can be replaced with another a neutral amino acid (e.g. threonine serine), a charged amino acid can be replaced with another charged amino acid (e.g. glutamate aspartate), a hydrophilic amino acid acid can be replaced with another hydrophilic amino acid (e.g. asparagine glutamine), a hydrophobic amino acid can be replaced with another hydrophobic amino acid (e.g. , alanine with valine), a polar amino acid can be replaced by another polar amino acid (for example, serine threonine), an aromatic amino acid can be replaced with another aromatic amino acid (for example, phenylalanine with tryptophan), and an aliphatic amino acid can be replaced with another aliphatic amino acid (for example, leucine with isoleucine) .

Preferred embodiments include those in which, instead of an amino acid that appears in the sequence, a structural analogue of the amino acid is contained.

Epitope and paratope

As used herein, the term “epitope” is defined in the context of the molecular interaction between an “antigen-binding polypeptide,” such as an antibody (Ab), and its corresponding antigen (Ag). Typically, "epitope" refers to the region or region on the Ag to which the Ab binds, i.e., the region or region of physical contact with the Ab. Physical contact can be defined using various criteria (e.g. distance limit 2–6 Å, such as 3 Å, such as 3.5 Å, such as 4 Å, such as 4.5 Å, such as 5 Å, or accessibility for solvent) for atoms in Ab and Ag molecules.

FIX/FIXa and FX/FXa may contain a variety of different epitopes, which may include, but are not limited to: (1) linear peptide epitopes, (2) conformational epitopes, which consist of one or more non-contiguous amino acids located adjacent to each other in the mature conformation FIX/FIXa or FX/FXa; and (3) epitopes, which consist in whole or in part of molecular structures covalently attached to FIX/FIXa or FX/FXa, such as carbohydrate groups.

The epitope for a given antibody (Ab)/antigen (Ag) pair can be described and characterized at different levels of detail using various experimental and computational epitope mapping techniques. Experimental methods include mutagenesis, x-ray crystallography, nuclear magnetic resonance (NMR) spectroscopy, hydrogen-deuterium exchange mass spectrometry (HDX-MS) and various competitive binding methods; methods that are known from the prior art. Because each method is based on a unique principle, the description of an epitope is closely related to the method by which it was determined. Thus, depending on the epitope mapping method used, the epitope for a given Ab/Ag pair may be described differently.

In the context of an X-ray crystal structure defined by the spatial coordinates of the complex between an Ab, such as a Fab fragment, and its Ag, the term “epitope” herein, unless otherwise noted or inconsistent with context, is specifically defined as FIX/FIXa residues or FX/FXa, characterized by the presence of a heavy atom (i.e., an atom other than hydrogen) at a distance of 3.5 Å from the heavy atom in Ab.

Epitopes described at the amino acid level, such as those defined on the basis of X-ray structure, are considered to be identical if they contain the same set of amino acid residues. Epitopes are considered to overlap if at least one amino acid residue is common to the epitopes. Epitopes are considered to be distinct (unique) if there are no amino acid residues that are common to the epitopes.

The definition of the term "paratope" is derived from the above definition of "epitope" by reversing the visual angle. Thus, the term "paratope" refers to the zone or region on an antibody or fragment thereof to which the antigen binds, i.e., by which it comes into physical contact with the antigen.

In the context of an X-ray crystal structure defined by the spatial coordinates of the complex between an Ab, such as a Fab moiety, and its Ag, the term “paratope” as used herein, unless otherwise noted or contrary to context, is specifically defined as the Ab residues characterized by the presence of a heavy atom (i.e., an atom other than hydrogen) at a distance of 3.5 Å from the heavy atom in FIX/FIXa or FX/FXa.

The epitope and paratope for a given antibody (Ab)/antigen (Ag) pair can be identified by conventional methods. For example, the general location of an epitope can be determined by assessing the ability of an antibody to bind to various fragments or variants of FIX/FIXa or FX/FXa. Specific amino acids within FIX/FIXa or FX/FXa that come into contact with the antibody (epitope) and specific amino acids within the antibody that come into contact with FIX/FIXa or FX/FXa (paratope) can also be determined by conventional methods. For example, the antibody and the target molecule can be combined and the Ab:Ag complex can be crystallized. The crystal structure of the complex can be determined and used to identify specific sites of interaction between the antibody and its target.

Epitopes on an antigen may contain one or more hot spot residues, i.e. residues that are particularly important for interaction with the cognate antibody and where interactions mediated by the side chain of the hot spot residue contribute significantly to the energy binding for antibody/antigen interactions (Peng et al. (2014) PNAS 111, E2656–E2665). Hot spot residues can be identified by testing antigen variants (herein FIX/FIXa and FX) in which individual epitope residues have been replaced, for example by alanine, with respect to cognate antibody binding. If substitution of an epitope residue with alanine has a strong effect on antibody binding, then the epitope residue is considered a hot spot residue and is therefore of particular importance for antibody binding to the antigen.

Antibodies that bind to the same antigen can be characterized in terms of their ability to bind to their common antigen at the same time and can be subjected to "competitive binding"/"group sorting". In the context of the present invention, the term "grouping" refers to a method of grouping antibodies that bind to the same antigen. "Bundling" of antibodies can be based on the competitive binding of two antibodies to their common antigen in assays based on standard techniques.

The antibody "group" is determined using a reference antibody. If the second antibody is unable to bind to an antigen at the same time as the reference antibody, the second antibody is considered to be in the same “group” as the reference antibody. In this case, the reference and second antibodies competitively bind the same part of the antigen and are “competing antibodies.” If the second antibody is capable of binding to an antigen at the same time as the reference antibody, the second antibody is considered to be in a separate “group.” In this case, the reference and second antibodies do not competitively bind the same portion of the antigen and are referred to as “non-competing antibodies.”

“Grouping” of antibodies does not provide direct information about the epitope.

Competing antibodies, i.e. antibodies belonging to the same “group”, may have identical epitopes, overlapping epitopes, or even separate epitopes. The latter occurs if the reference antibody, bound to its epitope on the antigen, occupies the space necessary for the second antibody to come into contact with its epitope on the antigen (“steric hindrance”). Non-competing antibodies are usually characterized by individual epitopes. Thus, in some embodiments, the antibodies of the present invention will bind to the same epitope as at least one of the antibodies specifically disclosed herein.

Competition assays to determine whether an antibody competes for binding with an anti-FIX/FIXa antibody or an anti-FX/FXa antibody disclosed herein are known in the art. Exemplary competition assays include immunoassays (eg, ELISA assays, RIA assays), surface plasmon resonance assays (eg, using a BIAcore™ instrument), biolayer interferometry (ForteBio®), and flow cytometry.

Typically, a competition assay involves the use of a solid surface-bound or cell surface-expressed antigen, a FIX- or FIXa-binding antibody to be tested, and a reference antibody. The reference antibody is labeled and the test antibody is unlabeled. Competitive inhibition is measured by determining the amount of labeled reference antibody bound to a solid surface or cells in the presence of the test antibody. Typically, the antibody being tested is present in excess (eg, 1-fold, 5-fold, 10-fold, 20-fold, 100-fold, 1000-fold, 10,000-fold, or 100,000-fold). Antibodies identified as competing in a competition assay (i.e., competing antibodies) include antibodies that bind to the same epitope or overlapping epitopes as the reference antibody and antibodies that bind to an adjacent epitope that is sufficiently close to the epitope bound by the reference antibody. antibody to cause steric hindrance.

In an exemplary competition assay, a reference anti-FIX or anti-FIXa antibody is biotinylated using commercially available reagents. The biotinylated reference antibody is mixed with serial dilutions of the test antibody or unlabeled reference antibody (self-competition control), resulting in a mixture at various molar ratios (e.g., 1-, 5-, 10-, 20-, 100-, 1000-, 10000-, or 100,000-fold) of the test antibody (or unlabeled reference antibody) and the labeled reference antibody. The antibody mixture is added to an ELISA plate coated with FIX or FIXa polypeptide. The plate is then washed and horseradish peroxidase (HRP)-streptavidin is added to the plate as a detection reagent. The amount of labeled reference antibody bound to the target antigen is detected after addition of a chromogenic substrate (e.g., TMB (3,3',5,5'-tetramethylbenzidine) or ABTS (2,2"-azino-di-(3-ethylbenzthiazoline-6 -sulfonate)), which are known in the art. Optical density (OD units) data is obtained using a spectrometer (e.g., SpectraMax® M2 spectrometer (Molecular Devices)). The response (OD units) corresponding to zero percent inhibition is determined based on the wells without any competing antibody.The response (OD units) corresponding to 100% inhibition, i.e., the assay background value, is determined based on wells without any labeled reference antibody or test antibody. Percentage of inhibition of labeled reference antibody to FIX or FIXa test antibody (or unlabeled reference antibody) at each concentration is calculated as follows: % inhibition = (1- (OD units - 100% inhibition)/(0% inhibition - 100% inhibition))* 100.

One skilled in the art will appreciate that similar assays can be performed to determine whether two or more anti-FX/FXa antibodies share a common binding region, group, and/or competitive antigen binding. Those skilled in the art will also appreciate that competitive analysis can be performed using various detection systems known in the art.

A test antibody competes with a reference antibody for binding to antigen if an excess of one antibody (e.g., 1-, 5-, 10-, 20-, 100-, 1000-, 10,000-, or 100,000-fold excess) inhibits binding of the other antibody, e.g. at least 50%, 75%, 90%, 95% or 99%, as measured in a competitive binding assay.

Unless otherwise stated, competition is determined using the competitive ELISA assay described above.

The term "binding affinity" is used herein as a measure of the strength of a non-covalent interaction between two molecules, for example, an antibody or fragment thereof and an antigen. The term binding affinity is used to describe monovalent interactions.

The binding affinity between two molecules, such as an antibody or fragment thereof and an antigen, through a monovalent interaction can be quantified by determining the equilibrium dissociation constant (K _D ). K _D can be determined by measuring the kinetics of complex formation and dissociation, for example, using the surface plasmon resonance (SPR) method or the isothermal titration calorimetry (ITC) method. The rate constants corresponding to the association and dissociation of a monovalent complex are denoted as the association rate constant, k _a (or k _on ), and the dissociation rate constant, k _d (or k _off ), respectively. K _D is related to k _a and k _d through the equation K _D = k _d / k _a .

Following the above definition, the binding affinities associated with various molecular interactions, such as comparing the binding affinities of different antibodies for a given antigen, can be compared by comparing K _D values for individual antibody/antigen complexes.

The value of the dissociation constant can be determined directly by well known methods. Standard assays for assessing the binding ability of ligands, such as antibodies, to targets are known in the art and include, for example, ELISA, Western blotting, RIA and flow cytometry. The binding kinetics and binding affinity of an antibody can also be assessed using standard assays known in the art, such as SPR. However, preferably, isothermal titration calorimetry (ITC) can be used to measure the affinities of the antibody/target interaction, as well as to obtain thermodynamic parameters of the interaction.

A competitive binding assay can be performed in which the binding of an antibody to a target is compared with the binding of the target by another ligand of that target, such as another antibody.

The K _D of an antibody of the present invention for its target may be less than 100 μM, such as less than 10 μM, such as less than 9 μM, such as less than 8 μM, such as less than 7 μM, such as , less than 6 µM, such as less than 5 µM, such as less than 4 µM, such as less than 3 µM, such as less than 2 µM, such as less than 1 µM, such as less 0.9 µM, such as less than 0.8 µM, such as less than 0.7 µM, such as less than 0.6 µM, such as less than 0.5 µM, such as less than 0 .4 µM, such as less than 0.3 µM, such as less than 0.2 µM, such as less than 0.1 µM.

In one such embodiment, the antibody is a bispecific antibody comprising an anti-FX arm with a K _D for FX of less than 100 μM, such as less than 10 μM, such as less than 9 μM, such as less than 8 μM, such as less than 7 µM, such as less than 6 µM, such as less than 5 µM, such as less than 4 µM, such as less than 3 µM, such as less than 2 µM, such as, e.g. less than 1 µM, such as less than 0.9 µM, such as less than 0.8 µM, such as less than 0.7 µM, such as less than 0.6 µM, such as less than 0.5 µM, such as less than 0.4 µM, such as less than 0.3 µM, such as less than 0.2 µM, such as less than 0.1 µM, such as less than 0.09 µM, such as, less than 0.08 µM, such as, less than 0.07 µM, such as, less than 0.06 µM, such as, less than 0.05 µM, such as, less than 0.04 µM, such as less than 0.03 µM, such as less than 0.02 µM, such as less than 0.01 µM, such as less than 9 nM, such as less than 8 nM, such as less than 7 nM, such as less than 6 nM, such as less than 5 nM, such as less than 4 nM, such as less than 3 nM, such as less than 2 nM, such as less than 1 nM, such as less than 0.5 nM.

The antibodies and fragments of such antibodies described herein can be combined with other antibodies and antibody fragments known in the art to form bispecific, trispecific or multispecific antibody molecules. Compounds that mimic FVIII cofactor function have previously been generated using other FIX(a) and FX(a) binding domains, each of which could potentially replace the FIX(a) and/or FX(a) binding domains described herein. Thus, it is clear that the FIX(a) and FX(a) binding domains of the present invention are of independent interest as separate component molecules (intermediates) as parts of a bi-, tri- or polyspecific antibody containing at least one FIX binding (a) and/or FX(a) domain.

The activity of procoagulant antibodies, including bi-, tri- and polyspecific antibodies, can be determined using methods known in the art. Standard tests include thrombin generation test (TGT) in whole blood, clotting time measurements using thromboelastography (TEG), and FXa production assays.

Identity

As is known in the art, the term “identity” refers to the relationship between the sequences of two or more polypeptides, determined by sequence comparison. In the art, “identity” also means the degree of sequence relatedness between different polypeptides, determined by the number of matches between stretches of two or more amino acid residues. “Identity” measures the percentage of identical matches in the smaller of two or more sequences in alignments with gaps (if any) considered by a particular mathematical model or computer program (i.e., “algorithms”). The identity of related polypeptides can be easily calculated by known methods.

In the present invention, similarity and identity were determined using the Needleman algorithm (Needleman et al. J. Mol. Biol. 1970; 48:443–453) in EMBOSS-6.6.0 using parameters 10 and 0.5 for introducing and extending gaps, respectively (gapopen=10, gapextend=0.5).

Pharmaceutical compounds

In another aspect of the present invention, compositions and formulations are provided containing compounds of the present invention, such as the antibodies described herein. For example, the present invention provides a pharmaceutical composition that contains one or more antibodies of the present invention formulated together with a pharmaceutically acceptable carrier.

Accordingly, one object of the present invention is to provide a pharmaceutical composition containing such an antibody which is present in a concentration of from 0.25 mg/ml to 250 mg/ml, and wherein said composition has a pH of from 2.0 to 10.0 . The composition may further contain one or more of a buffer system, a preservative, a tonicity control agent, a chelating agent, a stabilizer or a surfactant, as well as various combinations thereof. The use of preservatives, isotonic agents, chelating agents, stabilizers and surfactants in pharmaceutical compositions is well known to those skilled in the art. Reference may be made to Remington: The Science and Practice of Pharmacy, ^19th edition, 1995.

In one embodiment, the pharmaceutical composition is an aqueous composition. Such a composition is typically a solution or suspension, but may also include colloids, dispersions, emulsions and multiphase materials. The term "aqueous composition" is defined as a composition containing at least 50% w/w water. Likewise, the term "aqueous solution" is defined as a solution containing at least 50% w/w water, and the term "aqueous suspension" is defined as a suspension containing at least 50% w/w water.

In another embodiment, the pharmaceutical formulation is a lyophilized formulation to which a solvent and/or diluent is added prior to use.

In a further aspect, the pharmaceutical composition contains an aqueous solution of such antibody and a buffer, wherein the antibody is present at a concentration of 1 mg/ml or more, and wherein the composition has a pH of from about 2.0 to about 10.0.

In one embodiment, the present invention relates to an injection device containing the specified composition. In some embodiments, the pharmaceutical composition of the present invention is intended for use and/or is contained in an injection device. In some embodiments, the injection device is a disposable pre-filled multi-dose pen of the ^FlexTouch® type (supplied by Novo Nordisk A/S, Denmark). In some embodiments, the injection device is a single-acting device.

In some embodiments, the injection device is a fixed-dose device, such as a device configured to deliver multiple predetermined doses of a drug, sometimes referred to as a multiple fixed-dose device or a multiple-acting fixed-dose device.

In one embodiment, the pharmaceutical composition of the present invention is administered using an injection device containing a tube with a needle diameter of 20 or more.

In one embodiment, a bispecific antibody according to Table 1 herein is administered using an injection device comprising a tube with a needle diameter of 20 or greater.

In one embodiment, a bispecific antibody according to Table 1 herein is administered using an injection device comprising a tube having a needle diameter ranging from 20 to 36. In one such embodiment, the bispecific antibody is selected from the list consisting of bimAb05-0745, bimAb05-3761 , bimAb05-3761, bimAb05-2112, bimAb05-2113, bimAb05-2114, bimAb05-3769, bimAb05-4271, bimAb05-4756, bimAb05-0396, bimAb05-0417 and bimAb05-0438.

Administration and dosages

The compound of the present invention, such as an antibody, can be administered parenterally, for example intravenously, for example intramuscularly, for example subcutaneously. Alternatively, the antibody of the present invention can be administered by a non-parenteral route, for example orally or topically. The antibody of the present invention can be administered prophylactically. The antibody of the present invention can be administered therapeutically (if necessary).

The dose of the compounds to be delivered may be from about 0.01 mg to 500 mg of compound per day, preferably from about 0.1 mg to 250 mg per day, and more preferably from about 0.5 mg to about 250 mg per day, per week, per two weeks or per month as loading and maintenance doses, depending on the severity of the condition. An appropriate dose can also be adjusted for a particular compound based on the properties of that compound, including its in vivo half-life or mean retention time and its biological activity. For example, the compounds to be delivered may, in one embodiment, be administered once a week, or in another embodiment, once every two weeks, or in another embodiment, once a month, and in each of these embodiments at a dose for example, 0.025, 0.05, 0.075, 0.1, 0.125, 0.15, 0.175, 0.2, 0.25, 0.3, 0.35, 0.4, 0.45, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6, 5, 7, 7.5, 8, 8.5, 9, 9.5 or 10 mg per kg body weight.

Compositions containing the compounds disclosed herein can be administered for prophylactic and/or, in some embodiments, therapeutic treatment. In therapeutic applications, the compositions are administered to a subject already suffering from a disease, such as any bleeding disorder described above, in an amount sufficient to cure, alleviate or partially delay the progression of the disease and its complications. An amount sufficient to achieve this is defined as a "therapeutically effective amount". As will be appreciated by one skilled in the art, amounts effective for this purpose will depend on the severity of the disease or lesion, as well as the weight and general condition of the subject.

Embodiments

The present invention is further described by the following embodiments.

1. An antibody or antigen-binding fragment thereof capable of binding to factor IX (FIX) of SEQ ID NO:1 and/or its activated form (FIXa).

2. The antibody or antigen binding fragment thereof of Embodiment 1, wherein the antibody or antigen binding fragment thereof is part of the "group B" described herein.

3. The antibody or antigen-binding fragment thereof of Embodiment 1, wherein the antibody or antigen-binding fragment thereof competes with a reference antibody, wherein the reference antibody comprises:

a. a heavy chain variable domain identified under SEQ ID NO:35, and a light chain variable domain identified under SEQ ID NO:39,

b. a heavy chain variable domain identified by SEQ ID NO:43 and a light chain variable domain identified by SEQ ID NO:47, or

c. a heavy chain variable domain identified by SEQ ID NO:51 and a light chain variable domain identified by SEQ ID NO:55, or

d. a heavy chain variable domain identified by SEQ ID NO:67 and a light chain variable domain identified by SEQ ID NO:71, or

e. a heavy chain variable domain identified by SEQ ID NO:1202 and a light chain variable domain identified by SEQ ID NO:1206, or

f. a heavy chain variable domain identified by SEQ ID NO:1210 and a light chain variable domain identified by SEQ ID NO:1214, or

g. a heavy chain variable domain identified by SEQ ID NO:1218 and a light chain variable domain identified by SEQ ID NO:1222, or

h. a heavy chain variable domain identified by SEQ ID NO:1226 and a light chain variable domain identified by SEQ ID NO:1230, or

i. a heavy chain variable domain identified by SEQ ID NO:1234 and a light chain variable domain identified by SEQ ID NO:1238, or

j. a heavy chain variable domain identified under SEQ ID NO:1242, and a light chain variable domain identified under SEQ ID NO:1246.

4. The antibody or antigen binding fragment thereof according to the previous embodiment, wherein the reference antibody is a Fab.

5. The antibody or antigen binding fragment thereof according to any of the preceding embodiments, wherein the antibody or antigen binding fragment thereof comprises:

a. a heavy chain variable domain that is at least 90% identical to the sequence identified under SEQ ID NO:35 and a light chain variable domain that is at least 90% identical to the sequence identified under SEQ ID NO:39; or

b. a heavy chain variable domain that is at least 90% identical to the sequence identified under SEQ ID NO:43, and a light chain variable domain that is at least 90% identical to the sequence identified under SEQ ID NO:47; or

c. a heavy chain variable domain that is at least 90% identical to the sequence identified under SEQ ID NO:51 and a light chain variable domain that is at least 90% identical to the sequence identified under SEQ ID NO:55; or

d. a heavy chain variable domain that is at least 90% identical to the sequence identified under SEQ ID NO:67, and a light chain variable domain that is at least 90% identical to the sequence identified under SEQ ID NO:71, or

e. a heavy chain variable domain that is at least 90% identical to the sequence identified under SEQ ID NO:1202, and a light chain variable domain that is at least 90% identical to the sequence identified under SEQ ID NO:1206, or

f. a heavy chain variable domain that is at least 90% identical to the sequence identified under SEQ ID NO:1210, and a light chain variable domain that is at least 90% identical to the sequence identified under SEQ ID NO:1214, or

g. a heavy chain variable domain that is at least 90% identical to the sequence identified under SEQ ID NO:1218, and a light chain variable domain that is at least 90% identical to the sequence identified under SEQ ID NO:1222, or

h. a heavy chain variable domain that is at least 90% identical to the sequence identified under SEQ ID NO:1226, and a light chain variable domain that is at least 90% identical to the sequence identified under SEQ ID NO:1230, or

i. a heavy chain variable domain that is at least 90% identical to the sequence identified under SEQ ID NO:1234, and a light chain variable domain that is at least 90% identical to the sequence identified under SEQ ID NO:1238, or

j. a heavy chain variable domain that is at least 90% identical to the sequence identified under SEQ ID NO:1242; and a light chain variable domain that is at least 90% identical to the sequence identified under SEQ ID NO:1246.

6. The antibody or antigen binding fragment thereof of Embodiment 5, wherein the heavy chain variable domain is at least 92%, 94%, 96%, 97%, 98%, 99%, 99.1%, or 99.2% identical to the sequence identified under SEQ ID NO: 35, 43, 51, 67, 1202, 1210, 1218, 1226, 1234 or 1242 respectively.

7. The antibody or antigen binding fragment thereof of Embodiment 5, wherein the light chain variable domain is at least 92%, 94%, 96%, 97%, 98%, 99%, 99.1%, or 99.2% identical to the sequence identified under SEQ ID NO: 39, 47, 55, 71, 1206, 1214, 1222, 1230, 1238 or 1246 respectively.

8. The antibody or antigen binding fragment thereof of embodiments 6 and 7, wherein both the heavy chain variable domain and the light chain variable domain are at least 92, 94, 96, 97, 98, 99, 99.1 or 99.2 % identical to identified SEQ IDs.

9. The antibody or antigen binding fragment thereof according to any of the preceding embodiments, wherein the antibody or antigen binding fragment thereof is capable of binding an epitope comprising one or more of amino acid residues L337, R338, S339, T340, K341 and T343 of SEQ ID NO:1.

10. The antibody or antigen binding fragment thereof according to any of the preceding embodiments, wherein the antibody or antigen binding fragment thereof is capable of binding an epitope comprising amino acid residue R338 of SEQ ID NO:1.

11. The antibody or antigen binding fragment thereof according to any of the preceding embodiments, wherein the antibody or antigen binding fragment thereof is capable of binding an epitope comprising amino acid residues R338 and K341 of SEQ ID NO:1.

12. The antibody or antigen binding fragment thereof according to any of the preceding embodiments, wherein the antibody or antigen binding fragment thereof is capable of binding an epitope comprising two or three amino acid residues L337, R338, S339, T340, K341 and T343 of SEQ ID NO:1.

13. The antibody or antigen binding fragment thereof according to any of the preceding embodiments, wherein the antibody or antigen binding fragment thereof is capable of binding an epitope comprising four or five amino acid residues L337, R338, S339, T340, K341 and T343 of SEQ ID NO:1.

14. The antibody or antigen binding fragment thereof according to any of the preceding embodiments, wherein the antibody or antigen binding fragment thereof is capable of binding an epitope comprising:

a. R338, S339, T340, K341 and T343,

b. L337, S339, T340, K341 and T343,

c. L337, R338, T340, K341 and T343,

d. L337, R338, S339, K341 and T343,

e. L337, R338, S339, T340 and T343,

f. L337, R338, S339, T340 and K341,

g. L337, R338, S339 and T340 or

h. R338, T340 and K341

from SEQ ID NO:1.

15. The antibody or antigen-binding fragment thereof according to any one of embodiments 1-11, wherein the antibody or antigen-binding fragment thereof is capable of binding an epitope containing amino acid residues:

a. R338, T340 and K341 from SEQ ID NO:1 or

b. L337, R338, S339, T340 and K341 from SEQ ID NO:1.

16. The antibody or antigen-binding fragment thereof according to any of the previous embodiments, comprising a paratope containing the following amino acid residues:

a. H30, D31, W53, D56, S102, S104, Y106 and N107 in the heavy chain variable domain (SEQ ID NO:67) and Y91 and S92 in the light chain variable domain (SEQ ID NO:71), optionally containing one, two or three amino acid substitutions in the ten paratope amino acid residues listed, or

b. H30, D31, W53, S102, S104, Y106 and N107 in the heavy chain variable domain (SEQ ID NO:51) and residues Y91 and S92 in the light chain variable domain (SEQ ID NO: 55), optionally containing one, two or three amino acid substitutions in the nine listed amino acid residues of the paratope.

17. The antibody or antigen binding fragment thereof of any one of embodiments 1 to 16, comprising a paratope comprising the following amino acid residues D30, D31, W53, S102, S104 and N107 in the heavy chain variable domain (SEQ ID NO: 35) and Y91 and S92 in the light chain variable domain (SEQ ID NO: 39), optionally containing one, two or three amino acid substitutions in the eight listed amino acid residues of the paratope.

18. The antibody or antigen binding fragment thereof of embodiment 16 or 17, wherein said substitution(s) are conservative substitution(s).

19. The antibody or antigen-binding fragment thereof according to any of the previous embodiments, wherein the antibody or antigen-binding fragment thereof comprises:

a.

i. three heavy chain CDR sequences containing a maximum of 10 amino acid substitutions compared to the heavy chain variable domain CDR sequences identified under SEQ ID NO:35, and

ii. three light chain CDR sequences containing a maximum of 10 amino acid substitutions compared to the light chain variable domain CDR sequences identified under SEQ ID NO:39, or

b.

i. three heavy chain CDR sequences containing a maximum of 10 amino acid substitutions compared to the heavy chain variable domain CDR sequences identified under SEQ ID NO:43, and

ii. three light chain CDR sequences containing a maximum of 10 amino acid substitutions compared to the light chain variable domain CDR sequences identified under SEQ ID NO:47, or

c.

i. three heavy chain CDR sequences containing a maximum of 10 amino acid substitutions compared to the heavy chain variable domain CDR sequences identified under SEQ ID NO:51, and

ii. three light chain CDR sequences containing a maximum of 10 amino acid substitutions compared to the light chain variable domain CDR sequences identified under SEQ ID NO:55, or

d.

i. three heavy chain CDR sequences containing a maximum of 10 amino acid substitutions compared to the heavy chain variable domain CDR sequences identified under SEQ ID NO:67, and

ii. three light chain CDR sequences containing a maximum of 10 amino acid substitutions compared to the light chain variable domain CDR sequences identified under SEQ ID NO:71, or

e.

i. three heavy chain CDR sequences containing a maximum of 10 amino acid substitutions compared to the heavy chain variable domain CDR sequences identified under SEQ ID NO:1202, and

ii. three light chain CDR sequences containing a maximum of 10 amino acid substitutions compared to the light chain variable domain CDR sequences identified under SEQ ID NO:1206, or

f.

i. three heavy chain CDR sequences containing a maximum of 10 amino acid substitutions compared to the heavy chain variable domain CDR sequences identified under SEQ ID NO:1210, and

ii. three light chain CDR sequences containing a maximum of 10 amino acid substitutions compared to the light chain variable domain CDR sequences identified under SEQ ID NO:1214, or

g.

i. three heavy chain CDR sequences containing a maximum of 10 amino acid substitutions compared to the heavy chain variable domain CDR sequences identified under SEQ ID NO:1218, and

ii. three light chain CDR sequences containing a maximum of 10 amino acid substitutions compared to the light chain variable domain CDR sequences identified under SEQ ID NO:1222, or

h.

i. three heavy chain CDR sequences containing a maximum of 10 amino acid substitutions compared to the heavy chain variable domain CDR sequences identified under SEQ ID NO:1226, and

ii. three light chain CDR sequences containing a maximum of 10 amino acid substitutions compared to the light chain variable domain CDR sequences identified under SEQ ID NO:1230, or

i.

i. three heavy chain CDR sequences containing a maximum of 10 amino acid substitutions compared to the heavy chain variable domain CDR sequences identified under SEQ ID NO:1234, and

ii. three light chain CDR sequences containing a maximum of 10 amino acid substitutions compared to the light chain variable domain CDR sequences identified under SEQ ID NO:1238, or

j.

i. three heavy chain CDR sequences containing a maximum of 10 amino acid substitutions compared to the heavy chain variable domain CDR sequences identified under SEQ ID NO:1242, and

ii. three light chain CDR sequences containing a maximum of 10 amino acid substitutions compared to the light chain variable domain CDR sequences identified under SEQ ID NO:1246.

20. The antibody or antigen binding fragment thereof of Embodiment 19, wherein the three heavy chain CDR sequences contain a maximum of 9, such as 8, such as 7, or such as 6 amino acid substitutions compared to the CDRs of the identified SEQ IDs .

21. The antibody or antigen binding fragment thereof of Embodiment 19, wherein the three heavy chain CDR sequences contain a maximum of 5, such as 4, such as 3, such as 2, or a maximum of 1 amino acid substitution compared to the CDRs identified SEQ ID.

22. The antibody or antigen binding fragment thereof of Embodiment 19, wherein the three light chain CDR sequences contain a maximum of 9, such as 8, such as 7, or such as 6 amino acid substitutions compared to the CDRs of the identified SEQ IDs .

23. The antibody or antigen binding fragment thereof of Embodiment 19, wherein the three light chain CDR sequences contain a maximum of 5, such as 4, such as 3, such as 2, or a maximum of 1 amino acid substitution compared to the identified CDRs SEQ ID.

24. The antibody or antigen-binding fragment thereof according to any of the previous embodiments, wherein the antibody or antigen-binding fragment thereof comprises:

a. a CDR sequence from the heavy chain variable domain identified under SEQ ID NO:35 and a CDR sequence from the light chain variable domain identified under SEQ ID NO:39, or

b. a CDR sequence from the heavy chain variable domain identified under SEQ ID NO:43 and a CDR sequence from the light chain variable domain identified under SEQ ID NO:47, or

c. a CDR sequence from the heavy chain variable domain identified under SEQ ID NO:51 and a CDR sequence from the light chain variable domain identified under SEQ ID NO:55, or

d. a CDR sequence from the heavy chain variable domain identified under SEQ ID NO:67 and a CDR sequence from the light chain variable domain identified under SEQ ID NO:71, or

e. a CDR sequence from the heavy chain variable domain identified under SEQ ID NO:1202 and a CDR sequence from the light chain variable domain identified under SEQ ID NO:1206, or

f. a CDR sequence from the heavy chain variable domain identified under SEQ ID NO:1210 and a CDR sequence from the light chain variable domain identified under SEQ ID NO:1214, or

g. a CDR sequence from the heavy chain variable domain identified under SEQ ID NO:1218 and a CDR sequence from the light chain variable domain identified under SEQ ID NO:1222, or

h. a CDR sequence from the heavy chain variable domain identified under SEQ ID NO:1226 and a CDR sequence from the light chain variable domain identified under SEQ ID NO:1230, or

i. a CDR sequence from the heavy chain variable domain identified under SEQ ID NO:1234 and a CDR sequence from the light chain variable domain identified under SEQ ID NO:1238, or

j. a CDR sequence from the heavy chain variable domain identified under SEQ ID NO:1242, and a CDR sequence from the light chain variable domain identified under SEQ ID NO:1246.

25. The antibody or antigen-binding fragment thereof according to any of the previous embodiments, wherein the antibody or antigen-binding fragment thereof comprises:

a. a heavy chain variable domain identified by SEQ ID NO:35 and a light chain variable domain identified by SEQ ID NO:39, or

b. a heavy chain variable domain identified by SEQ ID NO:43 and a light chain variable domain identified by SEQ ID NO:47, or

c. a heavy chain variable domain identified by SEQ ID NO:51 and a light chain variable domain identified by SEQ ID NO:55, or

d. a heavy chain variable domain identified by SEQ ID NO:67 and a light chain variable domain identified by SEQ ID NO:71, or

e. a heavy chain variable domain identified by SEQ ID NO:1202 and a light chain variable domain identified by SEQ ID NO:1206, or

f. a heavy chain variable domain identified by SEQ ID NO:1210 and a light chain variable domain identified by SEQ ID NO:1214, or

g. a heavy chain variable domain identified by SEQ ID NO:1218 and a light chain variable domain identified by SEQ ID NO:1222, or

h. a heavy chain variable domain identified by SEQ ID NO:1226 and a light chain variable domain identified by SEQ ID NO:1230, or

i. a heavy chain variable domain identified by SEQ ID NO:1234 and a light chain variable domain identified by SEQ ID NO:1238, or

j. a heavy chain variable domain identified under SEQ ID NO:1242, and a light chain variable domain identified under SEQ ID NO:1246.

26. An antibody or antigen-binding fragment thereof capable of binding to FX (SEQ ID NO:2) and/or its activated form (FXa).

27. The antibody or antigen binding fragment thereof of embodiment 26, wherein the antibody or antigen binding fragment thereof is part of "group 2".

28. The antibody or antigen-binding fragment thereof of embodiment 26, wherein the antibody or antigen-binding fragment thereof competes with a reference antibody, wherein the reference antibody comprises:

a. a heavy chain variable domain identified by SEQ ID NO:467 and a light chain variable domain identified by SEQ ID NO:471, or

b. a heavy chain variable domain identified by SEQ ID NO:483 and a light chain variable domain identified by SEQ ID NO:487, or

c. a heavy chain variable domain identified by SEQ ID NO:707 and a light chain variable domain identified by SEQ ID NO:711, or

d. a heavy chain variable domain identified by SEQ ID NO:731 and a light chain variable domain identified by SEQ ID NO:735, or

e. a heavy chain variable domain identified by SEQ ID NO:907 and a light chain variable domain identified by SEQ ID NO:911, or

f. a heavy chain variable domain identified under SEQ ID NO:1075, and a light chain variable domain identified under SEQ ID NO:1079.

29. The antibody of any one of the previous embodiments, wherein the reference antibody is a Fab.

30. The antibody or antigen-binding fragment thereof according to any of the preceding embodiments, wherein the antibody or antigen-binding fragment thereof comprises a heavy chain variable domain that is at least 90% identical to the sequence identified under SEQ ID NO: 467, 483, 707, 731, 907 or 1075, and a light chain variable domain that is at least 90% identical to the sequence identified under SEQ ID NO:471, 487, 711, 735, 911 or 1079.

31. The antibody or antigen binding fragment thereof of Embodiment 30, wherein the heavy chain variable domain is at least 92%, 94%, 96%, 97%, 98%, 99%, 99.1%, or 99.2% identical to the sequence identified under SEQ ID NO: 467, 483, 707, 731, 907 or 1075.

32. The antibody or antigen binding fragment thereof of Embodiment 30, wherein the light chain variable domain is at least 92%, 94%, 96%, 97%, 98%, 99%, 99.1%, or 99.2% identical to the sequence identified under SEQ ID NO: 471, 487, 711, 735, 911 or 1079.

33. The antibody or antigen binding fragment thereof of embodiments 31 and 32, wherein both the heavy chain variable domain and the light chain variable domain are at least 92, 94, 96, 97, 98, 99, or 99.1% identical to those identified by SEQ ID.

34. The antibody or antigen-binding fragment thereof according to any of the previous embodiments, wherein the antibody or antigen-binding fragment thereof is capable of binding an epitope containing one or more amino acid residues E103, Q104, V108, R113, T116, L117, D119, I125, T127, E228, F229, Y230, E266, R287, P291, I292, P304, L419, K420, D423, R424, M426, K427 and T428 from FX(a).

35. The antibody or antigen binding fragment thereof according to any of the preceding embodiments, wherein the antibody or antigen binding fragment thereof is capable of binding an epitope containing 15, 16, 17, 18, 19, 20, 21, 22, 23 or 24 amino acid residues E103, Q104, V108, R113, T116, L117, D119, I125, T127, E228, F229, Y230, E266, R287, P291, I292, P304, L419, K420, D423, R424, M426, K427 and T428 from FX(a)

36. The antibody or antigen binding fragment thereof according to any of the preceding embodiments, wherein the antibody or antigen binding fragment thereof is capable of binding an epitope comprising amino acid residues Y230, D423, R424 and K427 of FX(a).

37. The antibody or antigen-binding fragment thereof according to any of the previous embodiments, wherein the antibody or antigen-binding fragment thereof is capable of binding an epitope containing amino acid residues E103, Q104, V108, R113, T116, L117, D119, I125, T127, E228, F229, Y230 , E266, R287, P291, I292, P304, L419, K420, D423, R424, M426, K427 and T428 from FX(a).

38. An antibody or an antigen-binding fragment thereof according to any of the previous embodiments, comprising a paratope containing the following amino acid residues: K23, S25, G26, Y27, F29, W33, D52, S54, D55, F57, S77, H100, Y101, Y102, N103, S104 in the heavy chain variable domain (SEQ ID NO:467) and residues V29, S30, S31, Y33, Y50, Q52, S54, R55, R57 and D94 in the light chain variable domain (SEQ ID NO:471), optional containing one, two, three, four or five amino acid substitutions, deletions or insertions in the 26 listed amino acid residues of the paratope.

39. The antibody or antigen-binding fragment thereof according to any of the previous embodiments, wherein the antibody or antigen-binding fragment thereof is capable of binding an epitope containing one or more amino acid residues E103, Q104, V108, R113, T116, L117, A118, D119, I125, T127, S227, E228, Y230, R287, I292, L303, P304, L419, K420, D423, R424, M426, K427 and T428 from FX(a).

40. The antibody or antigen binding fragment thereof according to any of the preceding embodiments, wherein the antibody or antigen binding fragment thereof is capable of binding an epitope containing 15, 16, 17, 18, 19, 20, 21, 22, 23 or 24 amino acid residues E103, Q104, V108, R113, T116, L117, A118, D119, I125, T127, S227, E228, Y230, R287, I292, L303, P304, L419, K420, D423, R424, M426, K427 and T428 from FX(a).

41. The antibody or antigen-binding fragment thereof according to any of the previous embodiments, wherein the antibody or antigen-binding fragment thereof is capable of binding an epitope containing amino acid residues E103, Q104, V108, R113, T116, L117, D119, I125, T127, E228, F229, Y230 , E266, R287, P291, I292, P304, L419, K420, D423, R424, M426, K427 and T428 from FX(a).

42. The antibody or antigen-binding fragment thereof according to any of the previous embodiments, containing a paratope containing the following amino acid residues: K23, G24, S25, G26, Y27, W33, D52, S54, D55, Y57, S77, L99, H100, Y101, Y102, N103 and S104 in the heavy chain variable domain (SEQ ID NO:483) and residues S30, S31, Y33, Y50, Q52, S54, R55, R57, Y92 and D94 in the light chain variable domain (SEQ ID NO:487) , optionally containing one, two, three, four or five amino acid substitutions, deletions or insertions in the 27 listed amino acid residues of the paratope.

43. The antibody or antigen binding fragment thereof of embodiment 38 or 42, wherein said substitution(s) are conservative substitution(s).

44. The antibody or antigen-binding fragment thereof according to any one of embodiments 26-43, wherein the antibody or antigen-binding fragment thereof comprises:

a. three heavy chain CDR sequences containing a maximum of 10 amino acid substitutions compared to the heavy chain variable domain CDR sequences identified under SEQ ID NO:467, and

three light chain CDR sequences containing a maximum of 10 amino acid substitutions compared to the light chain variable domain CDR sequences identified under SEQ ID NO:471; or

b. three heavy chain CDR sequences containing a maximum of 10 amino acid substitutions compared to the heavy chain variable domain CDR sequences identified under SEQ ID NO:483, and

three light chain CDR sequences containing a maximum of 10 amino acid substitutions compared to the light chain variable domain CDR sequences identified under SEQ ID NO:487.

45. The antibody or antigen binding fragment thereof of Embodiment 44, wherein the three heavy chain CDR sequences contain a maximum of 9, such as 8, such as 7, or such as 6 amino acid substitutions compared to the CDRs of the identified SEQ IDs .

46. The antibody or antigen binding fragment thereof of Embodiment 44, wherein the three heavy chain CDR sequences contain a maximum of 5, such as 4, such as 3, such as 2, or a maximum of 1 amino acid substitution compared to the CDRs identified SEQ ID.

47. The antibody or antigen binding fragment thereof of Embodiment 44, wherein the three light chain CDR sequences contain a maximum of 9, such as 8, such as 7, or, such as 6 amino acid substitutions compared to the CDRs of the identified SEQ IDs .

48. The antibody or antigen binding fragment thereof of Embodiment 44, wherein the three light chain CDR sequences contain a maximum of 5, such as 4, such as 3, such as 2, or a maximum of 1 amino acid substitution compared to the CDRs identified SEQ ID.

49. An antibody or antigen binding fragment thereof according to any of the preceding embodiments, wherein the antibody or antigen binding fragment thereof comprises CDR sequences of:

a. a heavy chain variable domain identified under SEQ ID NO:467 and a CDR sequence from a light chain variable domain identified under SEQ ID NO:471; or

b. a heavy chain variable domain identified under SEQ ID NO:483 and a CDR sequence from a light chain variable domain identified under SEQ ID NO:487; or

c. a heavy chain variable domain identified under SEQ ID NO:555 and a CDR sequence from a light chain variable domain identified under SEQ ID NO:559; or

d. a heavy chain variable domain identified under SEQ ID NO:587 and a CDR sequence from a light chain variable domain identified under SEQ ID NO:591; or

e. the heavy chain variable domain identified under SEQ ID NO:707 and the CDR sequence from the light chain variable domain identified under SEQ ID NO:711; or

f. the heavy chain variable domain identified under SEQ ID NO:731 and the CDR sequence from the light chain variable domain identified under SEQ ID NO:735; or

g. a heavy chain variable domain identified under SEQ ID NO:907 and a CDR sequence from a light chain variable domain identified under SEQ ID NO:911; or

h. the heavy chain variable domain identified under SEQ ID NO:1075, and the CDR sequence from the light chain variable domain identified under SEQ ID NO:1079.

50. The antibody or antigen binding fragment thereof according to any of the preceding embodiments, wherein the antibody or antigen binding fragment thereof comprises:

a. a heavy chain variable domain identified under SEQ ID NO:467 and a light chain variable domain identified under SEQ ID NO:471; or

b. a heavy chain variable domain identified under SEQ ID NO:483 and a light chain variable domain identified under SEQ ID NO:487; or

c. a heavy chain variable domain identified under SEQ ID NO:555 and a light chain variable domain identified under SEQ ID NO:559; or

d. a heavy chain variable domain identified under SEQ ID NO:587 and a light chain variable domain identified under SEQ ID NO:591; or

e. a heavy chain variable domain identified under SEQ ID NO:707 and a light chain variable domain identified under SEQ ID NO:711; or

f. a heavy chain variable domain identified under SEQ ID NO:731 and a light chain variable domain identified under SEQ ID NO:735; or

g. a heavy chain variable domain identified under SEQ ID NO:907 and a light chain variable domain identified under SEQ ID NO:911; or

h. a heavy chain variable domain identified under SEQ ID NO:1075, and a light chain variable domain identified under SEQ ID NO:1079.

51. A polyspecific antibody or antigen-binding fragment thereof capable of binding to FIX of SEQ ID NO:1 or an activated form thereof (FIXa) and FX (SEQ ID NO:2) or an activated form thereof (FXa).

52. The polyspecific antibody or antigen binding fragment thereof of embodiment 51, wherein the antibody comprises the antibody or antigen binding fragment thereof of any of the preceding embodiments 0-50.

53. The polyspecific antibody or antigen binding fragment thereof of embodiment 51, wherein the antibody comprises the antibody or antigen binding fragment thereof of any of the preceding embodiments 2-25.

54. The polyspecific antibody or antigen binding fragment thereof of embodiment 51, wherein the antibody comprises the antibody or antigen binding fragment thereof of any of the preceding embodiments 26-50.

55. The polyspecific antibody or antigen binding fragment thereof of embodiment 51, wherein the antibody comprises the antibody or antigen binding fragment thereof of any of the preceding embodiments 27-50.

56. The polyspecific antibody or antigen binding fragment thereof of Embodiment 51, wherein the antibody comprises the antibody or antigen binding fragment thereof of any of the preceding embodiments 0-25 and the antigen binding fragment of any of the preceding embodiments 26-50.

57. The polyspecific antibody or antigen binding fragment thereof of Embodiment 51, wherein the antibody comprises the antibody or antigen binding fragment thereof of any of the preceding embodiments 2-25 and the antibody or antigen binding fragment thereof of any of the preceding embodiments 27-50.

58. A polyspecific antibody or antigen-binding fragment thereof according to any of embodiments 51–57, containing:

a. the anti-FIX(a) antibody heavy chain CDR3 sequence identified by SEQ ID NO:38, optionally containing 1, 2 or 3 amino acid substitutions and/or deletions and/or insertions; And
the anti-FIX(a) antibody light chain CDR3 sequence identified by SEQ ID NO:42, optionally containing 1, 2 or 3 amino acid substitutions and/or deletions and/or insertions; And
the anti-FX(a) antibody heavy chain CDR3 sequence identified by SEQ ID NO:470, optionally containing 1, 2 or 3 amino acid substitutions and/or deletions and/or insertions; And
the anti-FX(a) antibody light chain CDR3 sequence identified under SEQ ID NO:474, optionally containing 1, 2 or 3 amino acid substitutions and/or deletions and/or insertions; or

b. the anti-FIX(a) antibody heavy chain CDR3 sequence identified by SEQ ID NO:38, optionally containing 1, 2 or 3 amino acid substitutions and/or deletions and/or insertions; And
the anti-FIX(a) antibody light chain CDR3 sequence identified by SEQ ID NO:42, optionally containing 1, 2 or 3 amino acid substitutions and/or deletions and/or insertions; And
the anti-FX(a) antibody heavy chain CDR3 sequence identified by SEQ ID NO:486, optionally containing 1, 2 or 3 amino acid substitutions and/or deletions and/or insertions; And
the anti-FX(a) antibody light chain CDR3 sequence identified by SEQ ID NO:490, optionally containing 1, 2 or 3 amino acid substitutions and/or deletions and/or insertions; or

c. the anti-FIX(a) antibody heavy chain CDR3 sequence identified by SEQ ID NO:46, optionally containing 1, 2 or 3 amino acid substitutions and/or deletions and/or insertions; And
the anti-FIX(a) antibody light chain CDR3 sequence identified by SEQ ID NO:50, optionally containing 1, 2 or 3 amino acid substitutions and/or deletions and/or insertions; And
the anti-FX(a) antibody heavy chain CDR3 sequence identified by SEQ ID NO:470, optionally containing 1, 2 or 3 amino acid substitutions and/or deletions and/or insertions; And
the anti-FX(a) antibody light chain CDR3 sequence identified under SEQ ID NO:474, optionally containing 1, 2 or 3 amino acid substitutions and/or deletions and/or insertions; or

d. the anti-FIX(a) antibody heavy chain CDR3 sequence identified by SEQ ID NO:54, optionally containing 1, 2 or 3 amino acid substitutions and/or deletions and/or insertions; And
the anti-FIX(a) antibody light chain CDR3 sequence identified by SEQ ID NO:58, optionally containing 1, 2 or 3 amino acid substitutions and/or deletions and/or insertions; And
the anti-FX(a) antibody heavy chain CDR3 sequence identified by SEQ ID NO:470, optionally containing 1, 2 or 3 amino acid substitutions and/or deletions and/or insertions; And
the anti-FX(a) antibody light chain CDR3 sequence identified under SEQ ID NO:474, optionally containing 1, 2 or 3 amino acid substitutions and/or deletions and/or insertions; or

e. the anti-FIX(a) antibody heavy chain CDR3 sequence identified by SEQ ID NO:54, optionally containing 1, 2 or 3 amino acid substitutions and/or deletions and/or insertions; And
the anti-FIX(a) antibody light chain CDR3 sequence identified by SEQ ID NO:58, optionally containing 1, 2 or 3 amino acid substitutions and/or deletions and/or insertions; And
the anti-FX(a) antibody heavy chain CDR3 sequence identified by SEQ ID NO:486, optionally containing 1, 2 or 3 amino acid substitutions and/or deletions and/or insertions; And
the anti-FX(a) antibody light chain CDR3 sequence identified by SEQ ID NO:490, optionally containing 1, 2 or 3 amino acid substitutions and/or deletions and/or insertions; or

f. the anti-FIX(a) antibody heavy chain CDR3 sequence identified by SEQ ID NO:54, optionally containing 1, 2 or 3 amino acid substitutions and/or deletions and/or insertions; And
the anti-FIX(a) antibody light chain CDR3 sequence identified by SEQ ID NO:58, optionally containing 1, 2 or 3 amino acid substitutions and/or deletions and/or insertions; And
the anti-FX(a) antibody heavy chain CDR3 sequence identified by SEQ ID NO:558, optionally containing 1, 2 or 3 amino acid substitutions and/or deletions and/or insertions; And
the anti-FX(a) antibody light chain CDR3 sequence identified under SEQ ID NO:562, optionally containing 1, 2 or 3 amino acid substitutions and/or deletions and/or insertions; or

g. the anti-FIX(a) antibody heavy chain CDR3 sequence identified by SEQ ID NO:54, optionally containing 1, 2 or 3 amino acid substitutions and/or deletions and/or insertions; And
the anti-FIX(a) antibody light chain CDR3 sequence identified by SEQ ID NO:58, optionally containing 1, 2 or 3 amino acid substitutions and/or deletions and/or insertions; And
the anti-FX(a) antibody heavy chain CDR3 sequence identified under SEQ ID NO:590, optionally containing 1, 2 or 3 amino acid substitutions and/or deletions and/or insertions; And
the anti-FX(a) antibody light chain CDR3 sequence identified under SEQ ID NO:594, optionally containing 1, 2 or 3 amino acid substitutions and/or deletions and/or insertions; or

h. the anti-FIX(a) antibody heavy chain CDR3 sequence identified by SEQ ID NO:54, optionally containing 1, 2 or 3 amino acid substitutions and/or deletions and/or insertions; And
the anti-FIX(a) antibody light chain CDR3 sequence identified by SEQ ID NO:58, optionally containing 1, 2 or 3 amino acid substitutions and/or deletions and/or insertions; And
the anti-FX(a) antibody heavy chain CDR3 sequence identified by SEQ ID NO:710, optionally containing 1, 2 or 3 amino acid substitutions and/or deletions and/or insertions; And
the anti-FX(a) antibody light chain CDR3 sequence identified by SEQ ID NO:714, optionally containing 1, 2 or 3 amino acid substitutions and/or deletions and/or insertions; or

i. the anti-FIX(a) antibody heavy chain CDR3 sequence identified by SEQ ID NO:54, optionally containing 1, 2 or 3 amino acid substitutions and/or deletions and/or insertions; And
the anti-FIX(a) antibody light chain CDR3 sequence identified by SEQ ID NO:58, optionally containing 1, 2 or 3 amino acid substitutions and/or deletions and/or insertions; And
the anti-FX(a) antibody heavy chain CDR3 sequence identified by SEQ ID NO:734, optionally containing 1, 2 or 3 amino acid substitutions and/or deletions and/or insertions; And
the anti-FX(a) antibody light chain CDR3 sequence identified by SEQ ID NO:738, optionally containing 1, 2 or 3 amino acid substitutions and/or deletions and/or insertions; or

j. the anti-FIX(a) antibody heavy chain CDR3 sequence identified by SEQ ID NO:54, optionally containing 1, 2 or 3 amino acid substitutions and/or deletions and/or insertions; And
the anti-FIX(a) antibody light chain CDR3 sequence identified by SEQ ID NO:58, optionally containing 1, 2 or 3 amino acid substitutions and/or deletions and/or insertions; And
the anti-FX(a) antibody heavy chain CDR3 sequence identified by SEQ ID NO:910, optionally containing 1, 2 or 3 amino acid substitutions and/or deletions and/or insertions; And
the anti-FX(a) antibody light chain CDR3 sequence identified under SEQ ID NO:914, optionally containing 1, 2 or 3 amino acid substitutions and/or deletions and/or insertions; or

k. the anti-FIX(a) antibody heavy chain CDR3 sequence identified by SEQ ID NO:54, optionally containing 1, 2 or 3 amino acid substitutions and/or deletions and/or insertions; And
the anti-FIX(a) antibody light chain CDR3 sequence identified by SEQ ID NO:58, optionally containing 1, 2 or 3 amino acid substitutions and/or deletions and/or insertions; And
the anti-FX(a) antibody heavy chain CDR3 sequence identified under SEQ ID NO:1078, optionally containing 1, 2 or 3 amino acid substitutions and/or deletions and/or insertions; And
the anti-FX(a) antibody light chain CDR3 sequence identified under SEQ ID NO:1082, optionally containing 1, 2 or 3 amino acid substitutions and/or deletions and/or insertions; or

l. the anti-FIX(a) antibody heavy chain CDR3 sequence identified by SEQ ID NO:70, optionally containing 1, 2 or 3 amino acid substitutions and/or deletions and/or insertions; And
the anti-FIX(a) antibody light chain CDR3 sequence identified by SEQ ID NO:74, optionally containing 1, 2 or 3 amino acid substitutions and/or deletions and/or insertions; And
the anti-FX(a) antibody heavy chain CDR3 sequence identified by SEQ ID NO:470, optionally containing 1, 2 or 3 amino acid substitutions and/or deletions and/or insertions; And
the anti-FX(a) antibody light chain CDR3 sequence identified under SEQ ID NO:474, optionally containing 1, 2 or 3 amino acid substitutions and/or deletions and/or insertions; or

m. the anti-FIX(a) antibody heavy chain CDR3 sequence identified by SEQ ID NO:70, optionally containing 1, 2 or 3 amino acid substitutions and/or deletions and/or insertions; And
the anti-FIX(a) antibody light chain CDR3 sequence identified by SEQ ID NO:74, optionally containing 1, 2 or 3 amino acid substitutions and/or deletions and/or insertions; And
the anti-FX(a) antibody heavy chain CDR3 sequence identified by SEQ ID NO:486, optionally containing 1, 2 or 3 amino acid substitutions and/or deletions and/or insertions; And
the anti-FX(a) antibody light chain CDR3 sequence identified by SEQ ID NO:490, optionally containing 1, 2 or 3 amino acid substitutions and/or deletions and/or insertions; or

n. the anti-FIX(a) antibody heavy chain CDR3 sequence identified by SEQ ID NO:1205, optionally containing 1, 2 or 3 amino acid substitutions and/or deletions and/or insertions; And
the anti-FIX(a) antibody light chain CDR3 sequence identified under SEQ ID NO:1209, optionally containing 1, 2 or 3 amino acid substitutions and/or deletions and/or insertions; And
the anti-FX(a) antibody heavy chain CDR3 sequence identified under SEQ ID NO:1213, optionally containing 1, 2 or 3 amino acid substitutions and/or deletions and/or insertions; And
the anti-FX(a) antibody light chain CDR3 sequence identified under SEQ ID NO:1217, optionally containing 1, 2 or 3 amino acid substitutions and/or deletions and/or insertions; or

o. the anti-FIX(a) antibody heavy chain CDR3 sequence identified by SEQ ID NO:1221, optionally containing 1, 2 or 3 amino acid substitutions and/or deletions and/or insertions; And
the anti-FIX(a) antibody light chain CDR3 sequence identified by SEQ ID NO:1225, optionally containing 1, 2 or 3 amino acid substitutions and/or deletions and/or insertions; And
the anti-FX(a) antibody heavy chain CDR3 sequence identified by SEQ ID NO:470, optionally containing 1, 2 or 3 amino acid substitutions and/or deletions and/or insertions; And
the anti-FX(a) antibody light chain CDR3 sequence identified under SEQ ID NO:474, optionally containing 1, 2 or 3 amino acid substitutions and/or deletions and/or insertions; or

p. the anti-FIX(a) antibody heavy chain CDR3 sequence identified by SEQ ID NO:1229, optionally containing 1, 2 or 3 amino acid substitutions and/or deletions and/or insertions; And
the anti-FIX(a) antibody light chain CDR3 sequence identified by SEQ ID NO:1233, optionally containing 1, 2 or 3 amino acid substitutions and/or deletions and/or insertions; And
the anti-FX(a) antibody heavy chain CDR3 sequence identified by SEQ ID NO:470, optionally containing 1, 2 or 3 amino acid substitutions and/or deletions and/or insertions; And
the anti-FX(a) antibody light chain CDR3 sequence identified under SEQ ID NO:474, optionally containing 1, 2 or 3 amino acid substitutions and/or deletions and/or insertions; or

q. the anti-FIX(a) antibody heavy chain CDR3 sequence identified under SEQ ID NO:1237, optionally containing 1, 2 or 3 amino acid substitutions and/or deletions and/or insertions; And
the anti-FIX(a) antibody light chain CDR3 sequence identified under SEQ ID NO:1241, optionally containing 1, 2 or 3 amino acid substitutions and/or deletions and/or insertions; And
the anti-FX(a) antibody heavy chain CDR3 sequence identified by SEQ ID NO:470, optionally containing 1, 2 or 3 amino acid substitutions and/or deletions and/or insertions; And
the anti-FX(a) antibody light chain CDR3 sequence identified by SEQ ID NO:474, optionally containing 1, 2 or 3 amino acid substitutions and/or deletions and/or insertions; or

r. the anti-FIX(a) antibody heavy chain CDR3 sequence identified by SEQ ID NO:1245, optionally containing 1, 2 or 3 amino acid substitutions and/or deletions and/or insertions; And
the anti-FIX(a) antibody light chain CDR3 sequence identified under SEQ ID NO:1249, optionally containing 1, 2 or 3 amino acid substitutions and/or deletions and/or insertions; And
the anti-FX(a) antibody heavy chain CDR3 sequence identified by SEQ ID NO:470, optionally containing 1, 2 or 3 amino acid substitutions and/or deletions and/or insertions; And
the anti-FX(a) antibody light chain CDR3 sequence identified under SEQ ID NO:474, optionally containing 1, 2 or 3 amino acid substitutions and/or deletions and/or insertions; or

59. A polyspecific antibody or antigen-binding fragment thereof according to any of embodiments 51–57, containing:

a. anti-FIX(a) antibody heavy chain CDR1-3 sequences identified by SEQ ID NO:36, 37 and 38, respectively, optionally containing 1, 2 or 3 amino acid substitutions and/or deletions and/or insertions; And
anti-FIX(a) antibody light chain CDR1-3 sequences identified by SEQ ID NO:40, 41 and 42, respectively, optionally containing 1, 2 or 3 amino acid substitutions and/or deletions and/or insertions; And
anti-FX(a) antibody heavy chain CDR1-3 sequences identified by SEQ ID NO:468, 469 and 470, respectively, optionally containing 1, 2 or 3 amino acid substitutions and/or deletions and/or insertions; And
anti-FX(a) antibody light chain CDR1-3 sequences identified at SEQ ID NO:472, 473 and 474, respectively, optionally containing 1, 2 or 3 amino acid substitutions and/or deletions and/or insertions; or

b. anti-FIX(a) antibody heavy chain CDR1-3 sequences identified by SEQ ID NO:36, 37 and 38, respectively, optionally containing 1, 2 or 3 amino acid substitutions and/or deletions and/or insertions; And
anti-FIX(a) antibody light chain CDR1-3 sequences identified by SEQ ID NO:40, 41 and 42, respectively, optionally containing 1, 2 or 3 amino acid substitutions and/or deletions and/or insertions; And
anti-FX(a) antibody heavy chain CDR1-3 sequences identified by SEQ ID NO:484, 485 and 486, respectively, optionally containing 1, 2 or 3 amino acid substitutions and/or deletions and/or insertions; And
anti-FX(a) antibody light chain CDR1-3 sequences identified by SEQ ID NO:488, 489 and 490, respectively, optionally containing 1, 2 or 3 amino acid substitutions and/or deletions and/or insertions; or

c. anti-FIX(a) antibody heavy chain CDR1-3 sequences identified by SEQ ID NO:44, 45 and 46, respectively, optionally containing 1, 2 or 3 amino acid substitutions and/or deletions and/or insertions; And
anti-FIX(a) antibody light chain CDR1-3 sequences identified by SEQ ID NO:48, 49 and 50, respectively, optionally containing 1, 2 or 3 amino acid substitutions and/or deletions and/or insertions; And
anti-FX(a) antibody heavy chain CDR1-3 sequences identified by SEQ ID NO:468, 469 and 470, respectively, optionally containing 1, 2 or 3 amino acid substitutions and/or deletions and/or insertions; And
anti-FX(a) antibody light chain CDR1-3 sequences identified at SEQ ID NO:472, 473 and 474, respectively, optionally containing 1, 2 or 3 amino acid substitutions and/or deletions and/or insertions; or

d. anti-FIX(a) antibody heavy chain CDR1-3 sequences identified at SEQ ID NO:52, 53 and 54, respectively, optionally containing 1, 2 or 3 amino acid substitutions and/or deletions and/or insertions; And
anti-FIX(a) antibody light chain CDR1-3 sequences identified at SEQ ID NO:56, 57 and 58, respectively, optionally containing 1, 2 or 3 amino acid substitutions and/or deletions and/or insertions; And
anti-FX(a) antibody heavy chain CDR1-3 sequences identified at SEQ ID NO:468, 469 and 470, respectively, optionally containing 1, 2 or 3 amino acid substitutions and/or deletions and/or insertions; And
anti-FX(a) antibody light chain CDR1-3 sequences identified at SEQ ID NO:472, 473 and 474, respectively, optionally containing 1, 2 or 3 amino acid substitutions and/or deletions and/or insertions; or

e. anti-FIX(a) antibody heavy chain CDR1-3 sequences identified at SEQ ID NO:52, 53 and 54, respectively, optionally containing 1, 2 or 3 amino acid substitutions and/or deletions and/or insertions; And
anti-FIX(a) antibody light chain CDR1-3 sequences identified at SEQ ID NO:56, 57 and 58, respectively, optionally containing 1, 2 or 3 amino acid substitutions and/or deletions and/or insertions; And
anti-FX(a) antibody heavy chain CDR1-3 sequences identified by SEQ ID NOs: 708, 709 and 710, respectively, optionally containing 1, 2 or 3 amino acid substitutions and/or deletions and/or insertions; And
anti-FX(a) antibody light chain CDR1-3 sequences identified by SEQ ID NOs: 712, 713 and 714, respectively, optionally containing 1, 2 or 3 amino acid substitutions and/or deletions and/or insertions; or

f. anti-FIX(a) antibody heavy chain CDR1-3 sequences identified at SEQ ID NO:52, 53 and 54, respectively, optionally containing 1, 2 or 3 amino acid substitutions and/or deletions and/or insertions; And
anti-FIX(a) antibody light chain CDR1-3 sequences identified at SEQ ID NO:56, 57 and 58, respectively, optionally containing 1, 2 or 3 amino acid substitutions and/or deletions and/or insertions; And
anti-FX(a) antibody heavy chain CDR1-3 sequences identified by SEQ ID NOs: 732, 733 and 734, respectively, optionally containing 1, 2 or 3 amino acid substitutions and/or deletions and/or insertions; And
anti-FX(a) antibody light chain CDR1-3 sequences identified by SEQ ID NOs: 736, 737 and 738, respectively, optionally containing 1, 2 or 3 amino acid substitutions and/or deletions and/or insertions; or

g. anti-FIX(a) antibody heavy chain CDR1-3 sequences identified at SEQ ID NO:52, 53 and 54, respectively, optionally containing 1, 2 or 3 amino acid substitutions and/or deletions and/or insertions; And
anti-FIX(a) antibody light chain CDR1-3 sequences identified at SEQ ID NO:56, 57 and 58, respectively, optionally containing 1, 2 or 3 amino acid substitutions and/or deletions and/or insertions; And
anti-FX(a) antibody heavy chain CDR1-3 sequences identified at SEQ ID NO:908, 909 and 910, respectively, optionally containing 1, 2 or 3 amino acid substitutions and/or deletions and/or insertions; And
anti-FX(a) antibody light chain CDR1-3 sequences identified by SEQ ID NO:912, 913 and 914, respectively, optionally containing 1, 2 or 3 amino acid substitutions and/or deletions and/or insertions; or

h. anti-FIX(a) antibody heavy chain CDR1-3 sequences identified at SEQ ID NO:52, 53 and 54, respectively, optionally containing 1, 2 or 3 amino acid substitutions and/or deletions and/or insertions; And
anti-FIX(a) antibody light chain CDR1-3 sequences identified at SEQ ID NO:56, 57 and 58, respectively, optionally containing 1, 2 or 3 amino acid substitutions and/or deletions and/or insertions; And
anti-FX(a) antibody heavy chain CDR1-3 sequences identified by SEQ ID NOs: 1076, 1077 and 1078, respectively, optionally containing 1, 2 or 3 amino acid substitutions and/or deletions and/or insertions; And
anti-FX(a) antibody light chain CDR1-3 sequences identified by SEQ ID NOs: 1080, 1081 and 1082, respectively, optionally containing 1, 2 or 3 amino acid substitutions and/or deletions and/or insertions; or

i. anti-FIX(a) antibody heavy chain CDR1-3 sequences identified at SEQ ID NO:52, 53 and 54, respectively, optionally containing 1, 2 or 3 amino acid substitutions and/or deletions and/or insertions; And
anti-FIX(a) antibody light chain CDR1-3 sequences identified at SEQ ID NO:56, 57 and 58, respectively, optionally containing 1, 2 or 3 amino acid substitutions and/or deletions and/or insertions; And
anti-FX(a) antibody heavy chain CDR1-3 sequences identified at SEQ ID NO:484, 485 and 486, respectively, optionally containing 1, 2 or 3 amino acid substitutions and/or deletions and/or insertions; And
anti-FX(a) antibody light chain CDR1-3 sequences identified at SEQ ID NO:488, 489 and 490, respectively, optionally containing 1, 2 or 3 amino acid substitutions and/or deletions and/or insertions; or

j. anti-FIX(a) antibody heavy chain CDR1-3 sequences identified by SEQ ID NOs: 68, 69 and 70, respectively, optionally containing 1, 2 or 3 amino acid substitutions and/or deletions and/or insertions; And
anti-FIX(a) antibody light chain CDR1-3 sequences identified by SEQ ID NOs: 72, 73 and 74, respectively, optionally containing 1, 2 or 3 amino acid substitutions and/or deletions and/or insertions; And
anti-FX(a) antibody heavy chain CDR1-3 sequences identified at SEQ ID NO:468, 469 and 470, respectively, optionally containing 1, 2 or 3 amino acid substitutions and/or deletions and/or insertions; And
anti-FX(a) antibody light chain CDR1-3 sequences identified at SEQ ID NO:472, 473 and 474, respectively, optionally containing 1, 2 or 3 amino acid substitutions and/or deletions and/or insertions; or

k. anti-FIX(a) antibody heavy chain CDR1-3 sequences identified by SEQ ID NOs: 68, 69 and 70, respectively, optionally containing 1, 2 or 3 amino acid substitutions and/or deletions and/or insertions; And
anti-FIX(a) antibody light chain CDR1-3 sequences identified by SEQ ID NOs: 72, 73 and 74, respectively, optionally containing 1, 2 or 3 amino acid substitutions and/or deletions and/or insertions; And
anti-FX(a) antibody heavy chain CDR1-3 sequences identified at SEQ ID NO:484, 485 and 486, respectively, optionally containing 1, 2 or 3 amino acid substitutions and/or deletions and/or insertions; And
anti-FX(a) antibody light chain CDR1-3 sequences identified at SEQ ID NO:488, 489 and 490, respectively, optionally containing 1, 2 or 3 amino acid substitutions and/or deletions and/or insertions; or

l. anti-FIX(a) antibody heavy chain CDR1-3 sequences identified by SEQ ID NOs: 1203, 1204 and 1205, respectively, optionally containing 1, 2 or 3 amino acid substitutions and/or deletions and/or insertions; And
anti-FIX(a) antibody light chain CDR1-3 sequences identified by SEQ ID NOs: 1207, 1208 and 1209, respectively, optionally containing 1, 2 or 3 amino acid substitutions and/or deletions and/or insertions; And
anti-FX(a) antibody heavy chain CDR1-3 sequences identified at SEQ ID NO:468, 469 and 470, respectively, optionally containing 1, 2 or 3 amino acid substitutions and/or deletions and/or insertions; And
anti-FX(a) antibody light chain CDR1-3 sequences identified at SEQ ID NO:472, 473 and 474, respectively, optionally containing 1, 2 or 3 amino acid substitutions and/or deletions and/or insertions; or

m. anti-FIX(a) antibody heavy chain CDR1-3 sequences identified by SEQ ID NOs: 1211, 1212 and 1213, respectively, optionally containing 1, 2 or 3 amino acid substitutions and/or deletions and/or insertions; And
anti-FIX(a) antibody light chain CDR1-3 sequences identified by SEQ ID NOs: 1215, 1216 and 1217, respectively, optionally containing 1, 2 or 3 amino acid substitutions and/or deletions and/or insertions; And
anti-FX(a) antibody heavy chain CDR1-3 sequences identified at SEQ ID NO:468, 469 and 470, respectively, optionally containing 1, 2 or 3 amino acid substitutions and/or deletions and/or insertions; And
anti-FX(a) antibody light chain CDR1-3 sequences identified at SEQ ID NO:472, 473 and 474, respectively, optionally containing 1, 2 or 3 amino acid substitutions and/or deletions and/or insertions; or

n. anti-FIX(a) antibody heavy chain CDR1-3 sequences identified by SEQ ID NOs: 1219, 1220 and 1221, respectively, optionally containing 1, 2 or 3 amino acid substitutions and/or deletions and/or insertions; And
anti-FIX(a) antibody light chain CDR1-3 sequences identified by SEQ ID NOs: 1223, 1224 and 1225, respectively, optionally containing 1, 2 or 3 amino acid substitutions and/or deletions and/or insertions; And
anti-FX(a) antibody heavy chain CDR1-3 sequences identified at SEQ ID NO:468, 469 and 470, respectively, optionally containing 1, 2 or 3 amino acid substitutions and/or deletions and/or insertions; And
anti-FX(a) antibody light chain CDR1-3 sequences identified at SEQ ID NO:472, 473 and 474, respectively, optionally containing 1, 2 or 3 amino acid substitutions and/or deletions and/or insertions; or

o. anti-FIX(a) antibody heavy chain CDR1-3 sequences identified by SEQ ID NOs: 1227, 1228 and 1229, respectively, optionally containing 1, 2 or 3 amino acid substitutions and/or deletions and/or insertions; And
anti-FIX(a) antibody light chain CDR1-3 sequences identified by SEQ ID NOs: 1231, 1232 and 1233, respectively, optionally containing 1, 2 or 3 amino acid substitutions and/or deletions and/or insertions; And
anti-FX(a) antibody heavy chain CDR1-3 sequences identified at SEQ ID NO:468, 469 and 470, respectively, optionally containing 1, 2 or 3 amino acid substitutions and/or deletions and/or insertions; And
anti-FX(a) antibody light chain CDR1-3 sequences identified at SEQ ID NO:472, 473 and 474, respectively, optionally containing 1, 2 or 3 amino acid substitutions and/or deletions and/or insertions; or

p. anti-FIX(a) antibody heavy chain CDR1-3 sequences identified by SEQ ID NOs: 1235, 1236 and 1237, respectively, optionally containing 1, 2 or 3 amino acid substitutions and/or deletions and/or insertions; And
anti-FIX(a) antibody light chain CDR1-3 sequences identified by SEQ ID NOs: 1239, 1240 and 1241, respectively, optionally containing 1, 2 or 3 amino acid substitutions and/or deletions and/or insertions; And
anti-FX(a) antibody heavy chain CDR1-3 sequences identified at SEQ ID NO:468, 469 and 470, respectively, optionally containing 1, 2 or 3 amino acid substitutions and/or deletions and/or insertions; And
anti-FX(a) antibody light chain CDR1-3 sequences identified at SEQ ID NO:472, 473 and 474, respectively, optionally containing 1, 2 or 3 amino acid substitutions and/or deletions and/or insertions; or

q. anti-FIX(a) antibody heavy chain CDR1-3 sequences identified by SEQ ID NOs: 1243, 1244 and 1245, respectively, optionally containing 1, 2 or 3 amino acid substitutions and/or deletions and/or insertions; And
anti-FIX(a) antibody light chain CDR1-3 sequences identified by SEQ ID NOs: 1247, 1248 and 1249, respectively, optionally containing 1, 2 or 3 amino acid substitutions and/or deletions and/or insertions; And
anti-FX(a) antibody heavy chain CDR1-3 sequences identified by SEQ ID NO:468, 469 and 470, respectively, optionally containing 1, 2 or 3 amino acid substitutions and/or deletions and/or insertions; And
anti-FX(a) antibody light chain CDR1-3 sequences identified at SEQ ID NO:472, 473 and 474, respectively, optionally containing 1, 2 or 3 amino acid substitutions and/or deletions and/or insertions.

60. A polyspecific antibody or antigen binding fragment thereof according to embodiment 51, wherein the antibody is a bispecific antibody capable of specifically binding FIX(a) and FX(a), wherein the binding domains are the binding domains of mAb pairs consisting of: mAb01-9933/mAb01 -8174, mAb01-9933/mAb01-9772, mAb01-9978/mAb01-8174, mAb01-9978/mAb01-9772, mAb01-9985/mAb01-8174, mAb01-9985/mAb01-9772, mAb01-99 94/mAb01-8174 , mAb01-9994/mAb01-9772, mAb01-9985/mAb11-1431, mAb01-9985/mAb11-1434, mAb01-9985/mAb11-1457, mAb01-9985/mAb11-1480, mAb01-9985/m Ab11-1121, mAb01 -9985/mAb11-1125, mAb11-0173/mAb01-8174, mAb11-1204/mAb01-8174, mAb11-1495/mAb01-8174, mAb11-1501/mAb01-8174 or mAb11-1502/mAb01-81 74.

61. The polyspecific antibody or antigen-binding fragment thereof according to any one of embodiments 51-60, wherein the antibody or antigen-binding fragment thereof is a procoagulant antibody.

62. The polyspecific antibody or antigen binding fragment thereof as in any one of embodiments 51-60, wherein the antibody or antigen binding fragment thereof is capable of increasing the procoagulant activity of FIXa.

63. The polyspecific antibody or antigen binding fragment thereof as in any one of embodiments 51-60, wherein the antibody or antigen binding fragment thereof is capable of increasing the enzymatic activity of FIXa towards FX.

64. The polyspecific antibody or antigen-binding fragment thereof according to any one of embodiments 51-60, wherein the antibody or antigen-binding fragment thereof is capable of functionally replacing FVIII and/or FVIIIa.

65. The polyspecific antibody or antigen binding fragment thereof as in any one of embodiments 51-64, wherein the antibody or antigen binding fragment thereof is a bispecific antibody.

66. The multispecific antibody or antigen-binding fragment thereof of any one of embodiments 63-65, wherein the increase in FIXa enzymatic activity toward FX is determined in the FXa production assay described herein using a monovalent single-arm anti-FIX/FIXa antibody, wherein the stimulation index is at least 1300-, 1400-, 1500-, 1600-, 1700-, 1800-, 1900-, 2000-, 2100-, 2200-, 2300-, 2400-, 2500-, 3000-, 3500-, 4000- , 4500-, 5000-, 5500-, 6000-, 6500-, 7000-, 7500-, 8000-, 8500-, 9000-, 9500-, 10000-, 10500-, 11000-, 11500-, 12000-, 1250 0 -, 13000-, 13500-, 13730, 14000-, 14500-, 15000-, 15500-, 16000-, 16500-, 17000-, 17500-, 18000-, 18500-, 19000- or 19500-fold at measurement using concentration of single-arm antibody resulting in at least 80% saturation of FIXa.

67. The polyspecific antibody or antigen-binding fragment thereof of any one of embodiments 51-65, wherein said antibody or antigen-binding fragment thereof is capable of producing an average peak thrombin level (in nM) of at least 47, 48, 49, 50, 55, 60 , 65, 70, 75, 80, 85, 90, 95, 100, 105, or 107, at a compound concentration of 900 nM in the TGT assay (in HA-PRP) according to Example 16 herein.

68. The antibody of any one of the preceding embodiments, wherein the isotype of the antibody is IgG1, IgG2, IgG3, or IgG4, or a combination thereof.

69. A pharmaceutical composition comprising an antibody or an antigen-binding fragment thereof according to any of the previous embodiments and optionally one or more pharmaceutically acceptable carriers.

70. A pharmaceutical composition comprising the antibody or antigen binding fragment thereof of embodiment 69 for the treatment of a coagulopathy or bleeding disorder such as hemophilia A with or without the presence of inhibitors.

71. An antibody or antigen-binding fragment or composition thereof according to any of the preceding embodiments for use in a method of treating a coagulopathy or bleeding disorder.

72. An antibody or antigen binding fragment or composition thereof according to any of the preceding embodiments for use in the treatment of hemophilia A with or without the presence of inhibitors.

73. A method of treating a subject suffering from a coagulopathy or bleeding disorder, comprising administering to the subject an antibody or antigen binding fragment or composition according to any of the preceding embodiments.

74. The method of embodiment 73, wherein the coagulopathy or bleeding disorder is hemophilia A or hemophilia A with inhibitors.

75. Use of the antibody or antigen-binding fragment or composition thereof of any one of embodiments 1-69 for the manufacture of a medicament for treating a subject in need thereof.

76. Use of the antibody or antigen-binding fragment or composition thereof of any one of embodiments 1-69 for the manufacture of a medicament for the treatment of hemophilia A, with or without the presence of inhibitors.

77. A eukaryotic cell that expresses the antibody or antigen-binding fragment thereof of any one of embodiments 1-68.

78. A kit containing the antibody or antigen-binding fragment or composition according to any of embodiments 1-69 and instructions for use.

79. The antibody or antigen binding fragment thereof according to any one of embodiments 1-25, wherein the antibody or antigen binding fragment thereof is a component (intermediate) for use in a procoagulant multispecific antibody.

80. The antibody or antigen binding fragment thereof as in any one of embodiments 26-50, wherein the antibody or antigen binding fragment thereof is a component (intermediate) for use in a procoagulant multispecific antibody.

81. The antibody or antigen binding fragment thereof according to any one of embodiments 1-25, wherein the antibody or antigen binding fragment thereof is a component (intermediate) for use in the manufacture of a procoagulant multispecific antibody.

82. The antibody or antigen binding fragment thereof as in any one of embodiments 26-50, wherein the antibody or antigen binding fragment thereof is a component (intermediate) for use in the manufacture of a procoagulant multispecific antibody.

83. The polyspecific antibody or antigen binding fragment thereof according to any one of embodiments 61-68, wherein the procoagulant activity of said antibody is increased compared to the polyspecific antibodies disclosed in WO2018/141863.

84. The polyspecific antibody or antigen binding fragment thereof of embodiment 83, wherein said increase is determined using an assay disclosed herein, such as the FXa production assay using monovalent single-arm (OA) anti-FIXa antibodies (described in Example 12 herein) , the TGT assay in plasma of patients with hemophilia A (HA) (described in Example 15 herein), in the TGT assay in HA-PPP or in the TGT assay in HA-PRP (described in Example 16 herein) or in a mouse tail vein transection (TVT) model (described in Example 17 herein).

85. The polyspecific antibody or antigen binding fragment thereof of Embodiment 51, wherein the antibody or antigen binding fragment thereof is a bispecific antibody comprising the antibody or antigen binding fragment thereof of Embodiment 14 and the antibody or antigen binding fragment thereof of Embodiment 36 or 37.

86. The multispecific antibody or antigen-binding fragment thereof of Embodiment 85, wherein stimulation of FIXa enzymatic activity toward FX is determined in the FXa production assay described in Example 12 herein using a monovalent single-arm anti-FIX/FIXa antibody, wherein the stimulation index is at least 1300-, 1400-, 1500-, 1600-, 1700-, 1800-, 1900-, 2000-, 2100-, 2200-, 2300-, 2400-, 2500-, 3000-, 3500-, 4000-, 4500-, 5000-, 5500-, 6000-, 6500-, 7000-, 7500-, 8000-, 8500-, 9000-, 9500-, 1000-, 10500-, 11000-, 11500-, 12000-, 12500- , 13000-, 13500-, 13730-, 14000-, 14500-, 15000-, 15500-, 16000-, 16500-, 17000-, 17500-, 18000-, 18500-, 19000- or 19500 times at measurement using concentration of single-arm antibody resulting in at least 80% saturation of FIXa.

87. The polyspecific antibody or antigen binding fragment thereof of embodiment 85, wherein said antibody or antigen binding fragment thereof is capable of providing an average peak thrombin level (in nM) of at least 47, 48, 49, 50, 55, 60, 65, 70 , 75, 80, 85, 90, 95, 100, 105, or 107, at a compound concentration of 900 nM in the TGT assay (in HA-PRP) according to Example 16 herein.

88. The antibody of any one of embodiments 85-87, wherein the isotype of the antibody is IgG1 or IgG4.

89. A pharmaceutical composition comprising the antibody or antigen-binding fragment thereof of any one of embodiments 85-88 and optionally one or more pharmaceutically acceptable carriers.

90. A pharmaceutical composition comprising the antibody or antigen binding fragment thereof of embodiment 89 for the treatment of a coagulopathy or bleeding disorder such as hemophilia A with or without the presence of inhibitors.

91. The antibody or antigen binding fragment or composition thereof of any one of embodiments 83-90 for use in a method of treating a coagulopathy or bleeding disorder.

92. The antibody or antigen binding fragment or composition thereof of embodiment 91 for use in the treatment of hemophilia A with or without the presence of inhibitors.

93. A method of treating a subject suffering from a coagulopathy or bleeding disorder, comprising administering to said subject an antibody or antigen binding fragment or composition according to any one of embodiments 83-90.

94. The method of embodiment 93, wherein the coagulopathy or bleeding disorder is hemophilia A or hemophilia A with inhibitors.

95. Use of the antibody or antigen binding fragment or composition thereof of any one of embodiments 83-89 for the manufacture of a medicament for treating a subject in need thereof.

96. Use of the antibody or antigen-binding fragment or composition thereof of any one of embodiments 83-89 for the manufacture of a medicament for the treatment of hemophilia A, with or without the presence of inhibitors.

97. A eukaryotic cell that expresses the antibody or antigen-binding fragment thereof of any one of embodiments 83-88.

98. A kit containing the antibody or antigen-binding fragment or composition according to any of embodiments 83-89 and instructions for use.

99. The antibody or antigen binding fragment thereof as in any one of embodiments 83-88, wherein the antibody or antigen binding fragment thereof capable of binding to FIX(a) is a component (intermediate) for use in a procoagulant multispecific antibody.

100. The antibody or antigen binding fragment thereof as in any one of embodiments 83-88, wherein the antibody or antigen binding fragment thereof capable of binding to FIX(a) is a component (intermediate) for use in the manufacture of a procoagulant multispecific antibody.

101. The antibody or antigen binding fragment thereof as in any one of embodiments 83-88, wherein the antibody or antigen binding fragment thereof is a component (intermediate) for use in the manufacture of a procoagulant multispecific antibody.

102. An injection device comprising an antibody or antigen-binding fragment or composition thereof according to any one of embodiments 51-69.

103. An injection device comprising an antibody or an antigen-binding fragment or composition thereof according to any one of embodiments 83-90.

104. The injection device of embodiment 102, wherein the device is a disposable and/or pre-filled and/or multi-dose device, such as a pen.

105. The injection device of embodiment 104, wherein said device is a pre-filled pen.

106. The injection device of embodiment 104, wherein said device is a multi-dose pen.

107. The injection device of any one of embodiments 102, 104, 105 or 106, wherein said injection device comprises a tube having a needle diameter of 20-36.

108. The injection device of embodiment 103, wherein said device is a disposable and/or pre-filled and/or multi-dose device, such as a pen.

109. The injection device of embodiment 103, wherein said device is a pre-filled pen.

110. The injection device of embodiment 108, wherein said device is a multi-dose pen.

111. The injection device of any one of embodiments 103, 108, 109 or 110, wherein said injection device comprises a tube having a needle diameter of 20-36.

In some embodiments, the antibodies or antigen binding fragments thereof of the present invention are procoagulant bispecific antibodies capable of binding to FIX (SEQ ID NO:1) and/or its activated form (FIXa) and to FX (SEQ ID NO:2) and/or or its activated form (FXa).

In one embodiment, the bispecific antibody (bimAb) is bimAb05-0745, wherein the arm to FIX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:68): DYAMH;

CDR2 VH (SEQ ID NO:69): GISWKGDIGGYVDSVKG;

CDR3 VH (SEQ ID NO:70): SYGSGSFYNAFDS;

CDR1 VL (SEQ ID NO:72): RASQSISSWLA;

CDR2 VL (SEQ ID NO:73): KASRLDR;

CDR3 VL (SEQ ID NO:74): LEYSSYIRT;

and where the arm to FX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:468): TSWIV;

CDR2 VH (SEQ ID NO:469): MIDPSDSFTSYSPSFQG;

CDR3 VH (SEQ ID NO:470): LHYYNSEEFDV;

CDR1 VL (SEQ ID NO:472): RASQSVSSSYLA;

CDR2 VL (SEQ ID NO:473): GQSSRTR;

CDR3 VL (SEQ ID NO:474): QQFGDSQLFT.

In one embodiment, the bispecific antibody is bimAb05-0746, wherein the arm to FIX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:44): DYAMH;

CDR2 VH (SEQ ID NO:45): GISWKGDIGGYVDSVKG;

CDR3 VH (SEQ ID NO:46): SYGSGSFYNAFDS;

CDR1 VL (SEQ ID NO:48): RASQSISSWLA;

CDR2 VL (SEQ ID NO:49): KASRLER;

CDR3 VL (SEQ ID NO:50): LEYSSYIRT;

and where the arm to FX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:468): TSWIV;

CDR2 VH (SEQ ID NO:469): MIDPSDSFTSYSPSFQG;

CDR3 VH (SEQ ID NO:470): LHYYNSEEFDV;

CDR1 VL (SEQ ID NO:472): RASQSVSSSYLA;

CDR2 VL (SEQ ID NO:473): GQSSRTR;

CDR3 VL (SEQ ID NO:474): QQFGDSQLFT.

In one embodiment, the bispecific antibody is bimAb05-1229, wherein the arm to FIX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:4): DYAMH;

CDR2 VH (SEQ ID NO:5): GISWRGDIGGYVDSVKG;

CDR3 VH (SEQ ID NO:6): SYGSGSFYNAFDS;

CDR1 VL (SEQ ID NO:8): RASQSISSWLA;

CDR2 VL (SEQ ID NO:9): KASRLER;

CDR3 VL (SEQ ID NO:10): LEYSSYIRT;

and where the arm to FX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:460): TSWIV;

CDR2 VH (SEQ ID NO:461): MIDPSDSFTSYSPSFQG;

CDR3 VH (SEQ ID NO:462): LHYYHSEEFDV;

CDR1 VL (SEQ ID NO:464): RASQSVSSSYLA;

CDR2 VL (SEQ ID NO:465): GASSRAR;

CDR3 VL (SEQ ID NO:466): QQFGSSRLFT.

In one embodiment, the bispecific antibody is bimAb05-2112, wherein the arm to FIX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:68): DYAMH;

CDR2 VH (SEQ ID NO:69): GISWKGDIGGYVDSVKG;

CDR3 VH (SEQ ID NO:70): SYGSGSFYNAFDS;

CDR1 VL (SEQ ID NO:72): RASQSISSWLA;

CDR2 VL (SEQ ID NO:73): KASRLDR;

CDR3 VL (SEQ ID NO:74): LEYSSYIRT;

and where the arm to FX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:484): TSWIS;

CDR2 VH (SEQ ID NO:485): MIDPSDSYTSYSPSFQG;

CDR3 VH (SEQ ID NO:486): LHYYNSEEFDV;

CDR1 VL (SEQ ID NO:488): RASQSVSSSYLA;

CDR2 VL (SEQ ID NO:489): GQSSRTR;

CDR3 VL (SEQ ID NO:490): QQYGDSQLFT.

In one embodiment, the bispecific antibody is bimAb05-2113, wherein the arm to FIX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:36): DYAMH;

CDR2 VH (SEQ ID NO:37): GISWKGDIGGYVDSVKG;

CDR3 VH (SEQ ID NO:38): SYGSGSFYNAFDS;

CDR1 VL (SEQ ID NO:40): RASQSISSWLA;

CDR2 VL (SEQ ID NO:41): KASKLDR;

CDR3 VL (SEQ ID NO:42): LEYSSYIRT;

and where the arm to FX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:484): TSWIS;

CDR2 VH (SEQ ID NO:485): MIDPSDSYTSYSPSFQG;

CDR3 VH (SEQ ID NO:486): LHYYNSEEFDV;

CDR1 VL (SEQ ID NO:488): RASQSVSSSYLA;

CDR2 VL (SEQ ID NO:489): GQSSRTR;

CDR3 VL (SEQ ID NO:490): QQYGDSQLFT.

In one embodiment, the bispecific antibody is bimAb05-2114, wherein the arm to FIX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:52): DYAMH;

CDR2 VH (SEQ ID NO:53): GISWRGDIGGYVKSVKG;

CDR3 VH (SEQ ID NO:54): SYGSGSFYNAFDS;

CDR1 VL (SEQ ID NO:56): RASQSISSWLA;

CDR2 VL (SEQ ID NO:57): KASKLER;

CDR3 VL (SEQ ID NO:58): LEYSSYIRT;

and where the arm to FX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:484): TSWIS;

CDR2 VH (SEQ ID NO:485): MIDPSDSYTSYSPSFQG;

CDR3 VH (SEQ ID NO:486): LHYYNSEEFDV;

CDR1 VL (SEQ ID NO:488): RASQSVSSSYLA;

CDR2 VL (SEQ ID NO:489): GQSSRTR;

CDR3 VL (SEQ ID NO:490): QQYGDSQLFT.

In one embodiment, the bispecific antibody is bimAb05-2115, wherein the arm to FIX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:44): DYAMH;

CDR2 VH (SEQ ID NO:45): GISWKGDIGGYVDSVKG;

CDR3 VH (SEQ ID NO:46): SYGSGSFYNAFDS;

CDR1 VL (SEQ ID NO:48): RASQSISSWLA;

CDR2 VL (SEQ ID NO:49): KASRLER;

CDR3 VL (SEQ ID NO:50): LEYSSYIRT;

and where the arm to FX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:484): TSWIS;

CDR2 VH (SEQ ID NO:485): MIDPSDSYTSYSPSFQG;

CDR3 VH (SEQ ID NO:486): LHYYNSEEFDV;

CDR1 VL (SEQ ID NO:488): RASQSVSSSYLA;

CDR2 VL (SEQ ID NO:489): GQSSRTR;

CDR3 VL (SEQ ID NO:490): QQYGDSQLFT.

In one embodiment, the bispecific antibody is bimAb05-2375, wherein the arm to FIX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:4): DYAMH;

CDR2 VH (SEQ ID NO:5): GISWRGDIGGYVDSVKG;

CDR3 VH (SEQ ID NO:6): SYGSGSFYNAFDS;

CDR1 VL (SEQ ID NO:8): RASQSISSWLA;

CDR2 VL (SEQ ID NO:9): KASRLER;

CDR3 VL (SEQ ID NO:10): LEYSSYIRT;

and where the arm to FX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:468): TSWIV;

CDR2 VH (SEQ ID NO:469): MIDPSDSFTSYSPSFQG;

CDR3 VH (SEQ ID NO:470): LHYYNSEEFDV;

CDR1 VL (SEQ ID NO:472): RASQSVSSSYLA;

CDR2 VL (SEQ ID NO:473): GQSSRTR;

CDR3 VL (SEQ ID NO:474): QQFGDSQLFT.

In one embodiment, the bispecific antibody is bimAb05-2379, wherein the arm to FIX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:4): DYAMH;

CDR2 VH (SEQ ID NO:5): GISWRGDIGGYVDSVKG;

CDR3 VH (SEQ ID NO:6): SYGSGSFYNAFDS;

CDR1 VL (SEQ ID NO:8): RASQSISSWLA;

CDR2 VL (SEQ ID NO:9): KASRLER;

CDR3 VL (SEQ ID NO:10): LEYSSYIRT;

and where the arm to FX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:476): TSWIV;

CDR2 VH (SEQ ID NO:477): MIDPSDSFTSYSPSFQG;

CDR3 VH (SEQ ID NO:478): LHYYNSEEFDV;

CDR1 VL (SEQ ID NO:480): RASQSVSSSYLA;

CDR2 VL (SEQ ID NO:481): GASSRAR;

CDR3 VL (SEQ ID NO:482): QQFGSSRLFT.

In one embodiment, the bispecific antibody is bimAb05-2532, wherein the arm to FIX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:12): DYAMH;

CDR2 VH (SEQ ID NO:13): GISWRGDIIGYVDSVKG;

CDR3 VH (SEQ ID NO:14): SYGSGSFYNAFDS;

CDR1 VL (SEQ ID NO:16): RASKSISSWLA;

CDR2 VL (SEQ ID NO:17): KASRLDR;

CDR3 VL (SEQ ID NO:18): LEYSSYIRT;

and where the arm to FX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:460): TSWIV;

CDR2 VH (SEQ ID NO:461): MIDPSDSFTSYSPSFQG;

CDR3 VH (SEQ ID NO:462): LHYYHSEEFDV;

CDR1 VL (SEQ ID NO:464): RASQSVSSSYLA;

CDR2 VL (SEQ ID NO:465): GASSRAR;

CDR3 VL (SEQ ID NO:466): QQFGSSRLFT.

In one embodiment, the bispecific antibody is bimAb05-3279, wherein the arm to FIX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:36): DYAMH;

CDR2 VH (SEQ ID NO:37): GISWKGDIGGYVDSVKG;

CDR3 VH (SEQ ID NO:38): SYGSGSFYNAFDS;

CDR1 VL (SEQ ID NO:40): RASQSISSWLA;

CDR2 VL (SEQ ID NO:41): KASKLDR;

CDR3 VL (SEQ ID NO:42): LEYSSYIRT;

and where the arm to FX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:460): TSWIV;

CDR2 VH (SEQ ID NO:461): MIDPSDSFTSYSPSFQG;

CDR3 VH (SEQ ID NO:462): LHYYHSEEFDV;

CDR1 VL (SEQ ID NO:464): RASQSVSSSYLA;

CDR2 VL (SEQ ID NO:465): GASSRAR;

CDR3 VL (SEQ ID NO:466): QQFGSSRLFT.

In one embodiment, the bispecific antibody is bimAb05-3409, wherein the arm to FIX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:44): DYAMH;

CDR2 VH (SEQ ID NO:45): GISWKGDIGGYVDSVKG;

CDR3 VH (SEQ ID NO:46): SYGSGSFYNAFDS;

CDR1 VL (SEQ ID NO:48): RASQSISSWLA;

CDR2 VL (SEQ ID NO:49): KASRLER;

CDR3 VL (SEQ ID NO:50): LEYSSYIRT;

and where the arm to FX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:460): TSWIV;

CDR2 VH (SEQ ID NO:461): MIDPSDSFTSYSPSFQG;

CDR3 VH (SEQ ID NO:462): LHYYHSEEFDV;

CDR1 VL (SEQ ID NO:464): RASQSVSSSYLA;

CDR2 VL (SEQ ID NO:465): GASSRAR;

CDR3 VL (SEQ ID NO:466): QQFGSSRLFT.

In one embodiment, the bispecific antibody is bimAb05-3416, wherein the arm to FIX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:52): DYAMH;

CDR2 VH (SEQ ID NO:53): GISWRGDIGGYVKSVKG;

CDR3 VH (SEQ ID NO:54): SYGSGSFYNAFDS;

CDR1 VL (SEQ ID NO:56): RASQSISSWLA;

CDR2 VL (SEQ ID NO:57): KASKLER;

CDR3 VL (SEQ ID NO:58): LEYSSYIRT;

and where the arm to FX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:460): TSWIV;

CDR2 VH (SEQ ID NO:461): MIDPSDSFTSYSPSFQG;

CDR3 VH (SEQ ID NO:462): LHYYHSEEFDV;

CDR1 VL (SEQ ID NO:464): RASQSVSSSYLA;

CDR2 VL (SEQ ID NO:465): GASSRAR;

CDR3 VL (SEQ ID NO:466): QQFGSSRLFT.

In one embodiment, the bispecific antibody is bimAb05-3755, wherein the arm to FIX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:68): DYAMH;

CDR2 VH (SEQ ID NO:69): GISWKGDIGGYVDSVKG;

CDR3 VH (SEQ ID NO:70): SYGSGSFYNAFDS;

CDR1 VL (SEQ ID NO:72): RASQSISSWLA;

CDR2 VL (SEQ ID NO:73): KASRLDR;

CDR3 VL (SEQ ID NO:74): LEYSSYIRT;

and where the arm to FX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:460): TSWIV;

CDR2 VH (SEQ ID NO:461): MIDPSDSFTSYSPSFQG;

CDR3 VH (SEQ ID NO:462): LHYYHSEEFDV;

CDR1 VL (SEQ ID NO:464): RASQSVSSSYLA;

CDR2 VL (SEQ ID NO:465): GASSRAR;

CDR3 VL (SEQ ID NO:466): QQFGSSRLFT.

In one embodiment, the bispecific antibody is bimAb05-3761, wherein the arm to FIX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:36): DYAMH;

CDR2 VH (SEQ ID NO:37): GISWKGDIGGYVDSVKG;

CDR3 VH (SEQ ID NO:38): SYGSGSFYNAFDS;

CDR1 VL (SEQ ID NO:40): RASQSISSWLA;

CDR2 VL (SEQ ID NO:41): KASKLDR;

CDR3 VL (SEQ ID NO:42): LEYSSYIRT;

and where the arm to FX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:468): TSWIV;

CDR2 VH (SEQ ID NO:469): MIDPSDSFTSYSPSFQG;

CDR3 VH (SEQ ID NO:470): LHYYNSEEFDV;

CDR1 VL (SEQ ID NO:472): RASQSVSSSYLA;

CDR2 VL (SEQ ID NO:473): GQSSRTR;

CDR3 VL (SEQ ID NO:474): QQFGDSQLFT.

In one embodiment, the bispecific antibody is bimAb05-3769, wherein the arm to FIX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:52): DYAMH;

CDR2 VH (SEQ ID NO:53): GISWRGDIGGYVKSVKG;

CDR3 VH (SEQ ID NO:54): SYGSGSFYNAFDS;

CDR1 VL (SEQ ID NO:56): RASQSISSWLA;

CDR2 VL (SEQ ID NO:57): KASKLER;

CDR3 VL (SEQ ID NO:58): LEYSSYIRT;

and where the arm to FX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:468): TSWIV;

CDR2 VH (SEQ ID NO:469): MIDPSDSFTSYSPSFQG;

CDR3 VH (SEQ ID NO:470): LHYYNSEEFDV;

CDR1 VL (SEQ ID NO:472): RASQSVSSSYLA;

CDR2 VL (SEQ ID NO:473): GQSSRTR;

CDR3 VL (SEQ ID NO:474): QQFGDSQLFT.

In one embodiment, the bispecific antibody is bimAb05-3770, wherein the arm to FIX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:60): DYAMH;

CDR2 VH (SEQ ID NO:61): GISWRGDIGGYVKSVKG;

CDR3 VH (SEQ ID NO:62): SYGSGSFYNAFDS;

CDR1 VL (SEQ ID NO:64): RASQSISSWLA;

CDR2 VL (SEQ ID NO:65): KASRLER;

CDR3 VL (SEQ ID NO:66): LEYSSYIRT;

and where the arm to FX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:468): TSWIV;

CDR2 VH (SEQ ID NO:469): MIDPSDSFTSYSPSFQG;

CDR3 VH (SEQ ID NO:470): LHYYNSEEFDV;

CDR1 VL (SEQ ID NO:472): RASQSVSSSYLA;

CDR2 VL (SEQ ID NO:473): GQSSRTR;

CDR3 VL (SEQ ID NO:474): QQFGDSQLFT.

In one embodiment, the bispecific antibody is bimAb05-3862, wherein the arm to FIX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:20): DYAMH;

CDR2 VH (SEQ ID NO:21): GISWRGDIGGYVDSVKG;

CDR3 VH (SEQ ID NO:22): SYGSGSFYNAFDS;

CDR1 VL (SEQ ID NO:24): RASQSISSWLA;

CDR2 VL (SEQ ID NO:25): KASRLDR;

CDR3 VL (SEQ ID NO:26): LEYSSYIRT;

and where the arm to FX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:468): TSWIV;

CDR2 VH (SEQ ID NO:469): MIDPSDSFTSYSPSFQG;

CDR3 VH (SEQ ID NO:470): LHYYNSEEFDV;

CDR1 VL (SEQ ID NO:472): RASQSVSSSYLA;

CDR2 VL (SEQ ID NO:473): GQSSRTR;

CDR3 VL (SEQ ID NO:474): QQFGDSQLFT.

In one embodiment, the bispecific antibody is bimAb05-3863, wherein the arm to FIX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:28): DYAMH;

CDR2 VH (SEQ ID NO:29): GISWRGDIGGYVDSVKG;

CDR3 VH (SEQ ID NO:30): SYGSGSFYNAFDS;

CDR1 VL (SEQ ID NO:32): RASQSISSWLA;

CDR2 VL (SEQ ID NO:33): KASRLER;

CDR3 VL (SEQ ID NO:34): LEYSSYIRT;

and where the arm to FX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:468): TSWIV;

CDR2 VH (SEQ ID NO:469): MIDPSDSFTSYSPSFQG;

CDR3 VH (SEQ ID NO:470): LHYYNSEEFDV;

CDR1 VL (SEQ ID NO:472): RASQSVSSSYLA;

CDR2 VL (SEQ ID NO:473): GQSSRTR;

CDR3 VL (SEQ ID NO:474): QQFGDSQLFT.

In one embodiment, the bispecific antibody is bimAb05-3880, wherein the arm to FIX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:76): DYAMH;

CDR2 VH (SEQ ID NO:77): GISWRGDIKGYVDSVKG;

CDR3 VH (SEQ ID NO:78): SYGSGSFYNAFDS;

CDR1 VL (SEQ ID NO:80): RASKSISSWLA;

CDR2 VL (SEQ ID NO:81): KASRLDR;

CDR3 VL (SEQ ID NO:82): LEYSSYIRT;

and where the arm to FX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:468): TSWIV;

CDR2 VH (SEQ ID NO:469): MIDPSDSFTSYSPSFQG;

CDR3 VH (SEQ ID NO:470): LHYYNSEEFDV;

CDR1 VL (SEQ ID NO:472): RASQSVSSSYLA;

CDR2 VL (SEQ ID NO:473): GQSSRTR;

CDR3 VL (SEQ ID NO:474): QQFGDSQLFT.

In one embodiment, the bispecific antibody is bimAb05-3886, wherein the arm to FIX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:84): DYAMH;

CDR2 VH (SEQ ID NO:85): GISWRGDIKGYVDSVKG;

CDR3 VH (SEQ ID NO:86): SYGSGSFYNAFDS;

CDR1 VL (SEQ ID NO:88): RASQSISSWLA;

CDR2 VL (SEQ ID NO:89): KASRLDR;

CDR3 VL (SEQ ID NO:90): LEYNSYIRT;

and where the arm to FX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:468): TSWIV;

CDR2 VH (SEQ ID NO:469): MIDPSDSFTSYSPSFQG;

CDR3 VH (SEQ ID NO:470): LHYYNSEEFDV;

CDR1 VL (SEQ ID NO:472): RASQSVSSSYLA;

CDR2 VL (SEQ ID NO:473): GQSSRTR;

CDR3 VL (SEQ ID NO:474): QQFGDSQLFT.

In one embodiment, the bispecific antibody is bimAb05-3955, wherein the arm to FIX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:92): DYAMH;

CDR2 VH (SEQ ID NO:93): GISWRGDIGGYVKSVKG;

CDR3 VH (SEQ ID NO:94): SYGSGSFYNAFDS;

CDR1 VL (SEQ ID NO:96): RASQSISSWLA;

CDR2 VL (SEQ ID NO:97): KAQRLDR;

CDR3 VL (SEQ ID NO:98): LEYSSYIRT;

and where the arm to FX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:468): TSWIV;

CDR2 VH (SEQ ID NO:469): MIDPSDSFTSYSPSFQG;

CDR3 VH (SEQ ID NO:470): LHYYNSEEFDV;

CDR1 VL (SEQ ID NO:472): RASQSVSSSYLA;

CDR2 VL (SEQ ID NO:473): GQSSRTR;

CDR3 VL (SEQ ID NO:474): QQFGDSQLFT.

In one embodiment, the bispecific antibody is bimAb05-4100, wherein the arm to FIX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:100): DYAMH;

CDR2 VH (SEQ ID NO:101): GISWKGDIGGYVDSVKG;

CDR3 VH (SEQ ID NO:102): SYGSGSFYNAFDS;

CDR1 VL (SEQ ID NO:104): RASQSIKSWLA;

CDR2 VL (SEQ ID NO:105): KASRLDR;

CDR3 VL (SEQ ID NO:106): LEYSSYIRT;

and where the arm to FX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:468): TSWIV;

CDR2 VH (SEQ ID NO:469): MIDPSDSFTSYSPSFQG;

CDR3 VH (SEQ ID NO:470): LHYYNSEEFDV;

CDR1 VL (SEQ ID NO:472): RASQSVSSSYLA;

CDR2 VL (SEQ ID NO:473): GQSSRTR;

CDR3 VL (SEQ ID NO:474): QQFGDSQLFT.

In one embodiment, the bispecific antibody is bimAb05-4114, wherein the arm to FIX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:108): DYAMH;

CDR2 VH (SEQ ID NO:109): GISWKGDIGGYADSVKG;

CDR3 VH (SEQ ID NO:110): SYGSGSFYNAFDS;

CDR1 VL (SEQ ID NO:112): RASKSISSWLA;

CDR2 VL (SEQ ID NO:113): KASRLER;

CDR3 VL (SEQ ID NO:114): LEYSSYIRT;

and where the arm to FX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:468): TSWIV;

CDR2 VH (SEQ ID NO:469): MIDPSDSFTSYSPSFQG;

CDR3 VH (SEQ ID NO:470): LHYYNSEEFDV;

CDR1 VL (SEQ ID NO:472): RASQSVSSSYLA;

CDR2 VL (SEQ ID NO:473): GQSSRTR;

CDR3 VL (SEQ ID NO:474): QQFGDSQLFT.

In one embodiment, the bispecific antibody is bimAb05-4121, wherein the arm to FIX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:116): DYAMH;

CDR2 VH (SEQ ID NO:117): GISWKGDIGGYADSVKG;

CDR3 VH (SEQ ID NO:118): SYGSGSFYNAFDS;

CDR1 VL (SEQ ID NO:120): RASQSISSWLA;

CDR2 VL (SEQ ID NO:121): KASRLER;

CDR3 VL (SEQ ID NO:122): LEYSSYIRT;

and where the arm to FX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:468): TSWIV;

CDR2 VH (SEQ ID NO:469): MIDPSDSFTSYSPSFQG;

CDR3 VH (SEQ ID NO:470): LHYYNSEEFDV;

CDR1 VL (SEQ ID NO:472): RASQSVSSSYLA;

CDR2 VL (SEQ ID NO:473): GQSSRTR;

CDR3 VL (SEQ ID NO:474): QQFGDSQLFT.

In one embodiment, the bispecific antibody is bimAb05-4220, wherein the arm to FIX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:212): DYAMH;

CDR2 VH (SEQ ID NO:213): GISWKGDIGGYADSVKG;

CDR3 VH (SEQ ID NO:214): SYGSGSFYNAFDS;

CDR1 VL (SEQ ID NO:216): RASQSISSWLA;

CDR2 VL (SEQ ID NO:217): KASKLDR;

CDR3 VL (SEQ ID NO:218): LEYSSYIRT;

and where the arm to FX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:468): TSWIV;

CDR2 VH (SEQ ID NO:469): MIDPSDSFTSYSPSFQG;

CDR3 VH (SEQ ID NO:470): LHYYNSEEFDV;

CDR1 VL (SEQ ID NO:472): RASQSVSSSYLA;

CDR2 VL (SEQ ID NO:473): GQSSRTR;

CDR3 VL (SEQ ID NO:474): QQFGDSQLFT.

In one embodiment, the bispecific antibody is bimAb05-4226, wherein the arm to FIX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:220): DYAMH;

CDR2 VH (SEQ ID NO:221): GISWKGDIGGYADSVKG;

CDR3 VH (SEQ ID NO:222): SYGSGSFYNAFDS;

CDR1 VL (SEQ ID NO:224): RASQSISSWLA;

CDR2 VL (SEQ ID NO:225): KASKLER;

CDR3 VL (SEQ ID NO:226): LEYSSYIRT;

and where the arm to FX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:468): TSWIV;

CDR2 VH (SEQ ID NO:469): MIDPSDSFTSYSPSFQG;

CDR3 VH (SEQ ID NO:470): LHYYNSEEFDV;

CDR1 VL (SEQ ID NO:472): RASQSVSSSYLA;

CDR2 VL (SEQ ID NO:473): GQSSRTR;

CDR3 VL (SEQ ID NO:474): QQFGDSQLFT.

In one embodiment, the bispecific antibody is bimAb05-4283, wherein the arm to FIX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:228): DYAMH;

CDR2 VH (SEQ ID NO:229): GISWKGDIGGYVDSVKG;

CDR3 VH (SEQ ID NO:230): SYGSGSFYNAFDS;

CDR1 VL (SEQ ID NO:232): RASQSISSWLA;

CDR2 VL (SEQ ID NO:233): KASKLDR;

CDR3 VL (SEQ ID NO:234): LEYSSYIRT;

and where the arm to FX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:468): TSWIV;

CDR2 VH (SEQ ID NO:469): MIDPSDSFTSYSPSFQG;

CDR3 VH (SEQ ID NO:470): LHYYNSEEFDV;

CDR1 VL (SEQ ID NO:472): RASQSVSSSYLA;

CDR2 VL (SEQ ID NO:473): GQSSRTR;

CDR3 VL (SEQ ID NO:474): QQFGDSQLFT.

In one embodiment, the bispecific antibody is bimAb05-4289, wherein the arm to FIX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:236): DYAMH;

CDR2 VH (SEQ ID NO:237): GISWKGDIGGYVDSVKG;

CDR3 VH (SEQ ID NO:238): SYGSGSFYNAFDS;

CDR1 VL (SEQ ID NO:240): RASQSISSWLA;

CDR2 VL (SEQ ID NO:241): KASKLER;

CDR3 VL (SEQ ID NO:242): LEYSSYIRT;

and where the arm to FX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:468): TSWIV;

CDR2 VH (SEQ ID NO:469): MIDPSDSFTSYSPSFQG;

CDR3 VH (SEQ ID NO:470): LHYYNSEEFDV;

CDR1 VL (SEQ ID NO:472): RASQSVSSSYLA;

CDR2 VL (SEQ ID NO:473): GQSSRTR;

CDR3 VL (SEQ ID NO:474): QQFGDSQLFT.

In one embodiment, the bispecific antibody is bimAb05-4292, wherein the arm to FIX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:252): DYAMH;

CDR2 VH (SEQ ID NO:253): GISWKGDIGGYVDSVKG;

CDR3 VH (SEQ ID NO:254): SYGSGSFYNAFDS;

CDR1 VL (SEQ ID NO:256): RASQSISSWLA;

CDR2 VL (SEQ ID NO:257): KASKLER;

CDR3 VL (SEQ ID NO:258): LEYSSYIRT;

and where the arm to FX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:468): TSWIV;

CDR2 VH (SEQ ID NO:469): MIDPSDSFTSYSPSFQG;

CDR3 VH (SEQ ID NO:470): LHYYNSEEFDV;

CDR1 VL (SEQ ID NO:472): RASQSVSSSYLA;

CDR2 VL (SEQ ID NO:473): GQSSRTR;

CDR3 VL (SEQ ID NO:474): QQFGDSQLFT.

In one embodiment, the bispecific antibody is bimAb05-4293, wherein the arm to FIX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:244): DYAMH;

CDR2 VH (SEQ ID NO:245): GISWKGDIGGYVDSVKG;

CDR3 VH (SEQ ID NO:246): SYGSGSFYNAFDS;

CDR1 VL (SEQ ID NO:248): RASQSISSWLA;

CDR2 VL (SEQ ID NO:249): KASKLDR;

CDR3 VL (SEQ ID NO:250): LEYSSYIRT;

and where the arm to FX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:468): TSWIV;

CDR2 VH (SEQ ID NO:469): MIDPSDSFTSYSPSFQG;

CDR3 VH (SEQ ID NO:470): LHYYNSEEFDV;

CDR1 VL (SEQ ID NO:472): RASQSVSSSYLA;

CDR2 VL (SEQ ID NO:473): GQSSRTR;

CDR3 VL (SEQ ID NO:474): QQFGDSQLFT.

In one embodiment, the bispecific antibody is bimAb05-4387, wherein the arm to FIX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:260): DYAMH;

CDR2 VH (SEQ ID NO:261): GISWKGDIGGYVDSVKG;

CDR3 VH (SEQ ID NO:262): SYGSGSFYNAFDS;

CDR1 VL (SEQ ID NO:264): RASQSISSWLA;

CDR2 VL (SEQ ID NO:265): KASKLDR;

CDR3 VL (SEQ ID NO:266): LEYSSYIRT;

and where the arm to FX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:468): TSWIV;

CDR2 VH (SEQ ID NO:469): MIDPSDSFTSYSPSFQG;

CDR3 VH (SEQ ID NO:470): LHYYNSEEFDV;

CDR1 VL (SEQ ID NO:472): RASQSVSSSYLA;

CDR2 VL (SEQ ID NO:473): GQSSRTR;

CDR3 VL (SEQ ID NO:474): QQFGDSQLFT.

In one embodiment, the bispecific antibody is bimAb05-4392, wherein the arm to FIX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:268): DYAMH;

CDR2 VH (SEQ ID NO:269): GISWKGDIGGYVDSVKG;

CDR3 VH (SEQ ID NO:270): SYGSGSFYNAFDS;

CDR1 VL (SEQ ID NO:272): RASQSISSWLA;

CDR2 VL (SEQ ID NO:273): KASKLER;

CDR3 VL (SEQ ID NO:274): LEYSSYIRT;

and where the arm to FX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:468): TSWIV;

CDR2 VH (SEQ ID NO:469): MIDPSDSFTSYSPSFQG;

CDR3 VH (SEQ ID NO:470): LHYYNSEEFDV;

CDR1 VL (SEQ ID NO:472): RASQSVSSSYLA;

CDR2 VL (SEQ ID NO:473): GQSSRTR;

CDR3 VL (SEQ ID NO:474): QQFGDSQLFT.

In one embodiment, the bispecific antibody is bimAb05-4419, wherein the arm to FIX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:124): DYAMH;

CDR2 VH (SEQ ID NO:125): GISWKGDIGGYVDSVKG;

CDR3 VH (SEQ ID NO:126): SYGSGSFYNAFDS;

CDR1 VL (SEQ ID NO:128): RASQSISSWLA;

CDR2 VL (SEQ ID NO:129): KASKLDR;

CDR3 VL (SEQ ID NO:130): LEYSSYIRT;

and where the arm to FX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:468): TSWIV;

CDR2 VH (SEQ ID NO:469): MIDPSDSFTSYSPSFQG;

CDR3 VH (SEQ ID NO:470): LHYYNSEEFDV;

CDR1 VL (SEQ ID NO:472): RASQSVSSSYLA;

CDR2 VL (SEQ ID NO:473): GQSSRTR;

CDR3 VL (SEQ ID NO:474): QQFGDSQLFT.

In one embodiment, the bispecific antibody is bimAb05-4422, wherein the arm to FIX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:276): DYAMH;

CDR2 VH (SEQ ID NO:277): GISWKGDIGGYVDSVKG;

CDR3 VH (SEQ ID NO:278): SYGSGSFYNAFDS;

CDR1 VL (SEQ ID NO:280): RASQSISSWLA;

CDR2 VL (SEQ ID NO:281): KASKLDR;

CDR3 VL (SEQ ID NO:282): LEYSSYIRT;

and where the arm to FX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:468): TSWIV;

CDR2 VH (SEQ ID NO:469): MIDPSDSFTSYSPSFQG;

CDR3 VH (SEQ ID NO:470): LHYYNSEEFDV;

CDR1 VL (SEQ ID NO:472): RASQSVSSSYLA;

CDR2 VL (SEQ ID NO:473): GQSSRTR;

CDR3 VL (SEQ ID NO:474): QQFGDSQLFT.

In one embodiment, the bispecific antibody is bimAb05-4428, wherein the arm to FIX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:284): DYAMH;

CDR2 VH (SEQ ID NO:285): GISWKGDIGGYVDSVKG;

CDR3 VH (SEQ ID NO:286): SYGSGSFYNAFDS;

CDR1 VL (SEQ ID NO:288): RASQSISSWLA;

CDR2 VL (SEQ ID NO:289): KASKLER;

CDR3 VL (SEQ ID NO:290): LEYSSYIRT;

and where the arm to FX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:468): TSWIV;

CDR2 VH (SEQ ID NO:469): MIDPSDSFTSYSPSFQG;

CDR3 VH (SEQ ID NO:470): LHYYNSEEFDV;

CDR1 VL (SEQ ID NO:472): RASQSVSSSYLA;

CDR2 VL (SEQ ID NO:473): GQSSRTR;

CDR3 VL (SEQ ID NO:474): QQFGDSQLFT.

In one embodiment, the bispecific antibody is bimAb05-4443, wherein the arm to FIX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:300): DYAMH;

CDR2 VH (SEQ ID NO:301): GISWKGDIGGYVDSVKG;

CDR3 VH (SEQ ID NO:302): SYGSGSFYNAFDS;

CDR1 VL (SEQ ID NO:304): RASQSISSWLA;

CDR2 VL (SEQ ID NO:305): KASKLER;

CDR3 VL (SEQ ID NO:306): LEYSSYIRT;

and where the arm to FX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:468): TSWIV;

CDR2 VH (SEQ ID NO:469): MIDPSDSFTSYSPSFQG;

CDR3 VH (SEQ ID NO:470): LHYYNSEEFDV;

CDR1 VL (SEQ ID NO:472): RASQSVSSSYLA;

CDR2 VL (SEQ ID NO:473): GQSSRTR;

CDR3 VL (SEQ ID NO:474): QQFGDSQLFT.

In one embodiment, the bispecific antibody is bimAb05-4444, wherein the arm to FIX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:292): DYAMH;

CDR2 VH (SEQ ID NO:293): GISWKGDIGGYVDSVKG;

CDR3 VH (SEQ ID NO:294): SYGSGSFYNAFDS;

CDR1 VL (SEQ ID NO:296): RASQSISSWLA;

CDR2 VL (SEQ ID NO:297): KASKLDR;

CDR3 VL (SEQ ID NO:298): LEYSSYIRT;

and where the arm to FX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:468): TSWIV;

CDR2 VH (SEQ ID NO:469): MIDPSDSFTSYSPSFQG;

CDR3 VH (SEQ ID NO:470): LHYYNSEEFDV;

CDR1 VL (SEQ ID NO:472): RASQSVSSSYLA;

CDR2 VL (SEQ ID NO:473): GQSSRTR;

CDR3 VL (SEQ ID NO:474): QQFGDSQLFT.

In one embodiment, the bispecific antibody is bimAb05-4601, wherein the arm to FIX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:188): DYAMH;

CDR2 VH (SEQ ID NO:189): GISWKGDIGGYVDSVKG;

CDR3 VH (SEQ ID NO:190): SYGSGSFYNAFDS;

CDR1 VL (SEQ ID NO:192): RASQSISSWLA;

CDR2 VL (SEQ ID NO:193): KASRLDR;

CDR3 VL (SEQ ID NO:194): LEYSSYIRT;

and where the arm to FX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:468): TSWIV;

CDR2 VH (SEQ ID NO:469): MIDPSDSFTSYSPSFQG;

CDR3 VH (SEQ ID NO:470): LHYYNSEEFDV;

CDR1 VL (SEQ ID NO:472): RASQSVSSSYLA;

CDR2 VL (SEQ ID NO:473): GQSSRTR;

CDR3 VL (SEQ ID NO:474): QQFGDSQLFT.

In one embodiment, the bispecific antibody is bimAb05-4604, wherein the arm to FIX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:140): DYAMH;

CDR2 VH (SEQ ID NO:141): GISWKGDIGGYVDSVKG;

CDR3 VH (SEQ ID NO:142): SYGSGSFYNAFDS;

CDR1 VL (SEQ ID NO:144): RASQSISSWLA;

CDR2 VL (SEQ ID NO:145): KASRLDR;

CDR3 VL (SEQ ID NO:146): LEYSSYIRT;

and where the arm to FX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:468): TSWIV;

CDR2 VH (SEQ ID NO:469): MIDPSDSFTSYSPSFQG;

CDR3 VH (SEQ ID NO:470): LHYYNSEEFDV;

CDR1 VL (SEQ ID NO:472): RASQSVSSSYLA;

CDR2 VL (SEQ ID NO:473): GQSSRTR;

CDR3 VL (SEQ ID NO:474): QQFGDSQLFT.

In one embodiment, the bispecific antibody is bimAb05-4608, wherein the arm to FIX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:204): DYAMH;

CDR2 VH (SEQ ID NO:205): GISWKGDIGGYVDSVKG;

CDR3 VH (SEQ ID NO:206): SYGSGSFYNAFDS;

CDR1 VL (SEQ ID NO:208): RASQSISSWLA;

CDR2 VL (SEQ ID NO:209): KASRLDR;

CDR3 VL (SEQ ID NO:210): LEYSSYIRT;

and where the arm to FX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:468): TSWIV;

CDR2 VH (SEQ ID NO:469): MIDPSDSFTSYSPSFQG;

CDR3 VH (SEQ ID NO:470): LHYYNSEEFDV;

CDR1 VL (SEQ ID NO:472): RASQSVSSSYLA;

CDR2 VL (SEQ ID NO:473): GQSSRTR;

CDR3 VL (SEQ ID NO:474): QQFGDSQLFT.

In one embodiment, the bispecific antibody is bimAb05-4611, wherein the arm to FIX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:180): DYAMH;

CDR2 VH (SEQ ID NO:181): GISWKGDIGGYVDSVKG;

CDR3 VH (SEQ ID NO:182): SYGSGSFYNAFDS;

CDR1 VL (SEQ ID NO:184): RASQSISSWLA;

CDR2 VL (SEQ ID NO:185): KASRLDR;

CDR3 VL (SEQ ID NO:186): LEYSSYIRT;

and where the arm to FX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:468): TSWIV;

CDR2 VH (SEQ ID NO:469): MIDPSDSFTSYSPSFQG;

CDR3 VH (SEQ ID NO:470): LHYYNSEEFDV;

CDR1 VL (SEQ ID NO:472): RASQSVSSSYLA;

CDR2 VL (SEQ ID NO:473): GQSSRTR;

CDR3 VL (SEQ ID NO:474): QQFGDSQLFT.

In one embodiment, the bispecific antibody is bimAb05-4612, wherein the arm to FIX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:196): DYAMH;

CDR2 VH (SEQ ID NO:197): GISWKGDIGGYVDSVKG;

CDR3 VH (SEQ ID NO:198): SYGSGSFYNAFDS;

CDR1 VL (SEQ ID NO:200): RASQSISSWLA;

CDR2 VL (SEQ ID NO:201): KASRLDR;

CDR3 VL (SEQ ID NO:202): LEYSSYIRT;

and where the arm to FX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:468): TSWIV;

CDR2 VH (SEQ ID NO:469): MIDPSDSFTSYSPSFQG;

CDR3 VH (SEQ ID NO:470): LHYYNSEEFDV;

CDR1 VL (SEQ ID NO:472): RASQSVSSSYLA;

CDR2 VL (SEQ ID NO:473): GQSSRTR;

CDR3 VL (SEQ ID NO:474): QQFGDSQLFT.

In one embodiment, the bispecific antibody is bimAb05-4613, wherein the arm to FIX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:172): DYAMH;

CDR2 VH (SEQ ID NO:173): GISWKGDIGGYVDSVKG;

CDR3 VH (SEQ ID NO:174): SYGSGSFYNAFDS;

CDR1 VL (SEQ ID NO:176): RASQSISSWLA;

CDR2 VL (SEQ ID NO:177): KASRLDR;

CDR3 VL (SEQ ID NO:178): LEYSSYIRT;

and where the arm to FX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:468): TSWIV;

CDR2 VH (SEQ ID NO:469): MIDPSDSFTSYSPSFQG;

CDR3 VH (SEQ ID NO:470): LHYYNSEEFDV;

CDR1 VL (SEQ ID NO:472): RASQSVSSSYLA;

CDR2 VL (SEQ ID NO:473): GQSSRTR;

CDR3 VL (SEQ ID NO:474): QQFGDSQLFT.

In one embodiment, the bispecific antibody is bimAb05-4615, wherein the arm to FIX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:164): DYAMH;

CDR2 VH (SEQ ID NO:165): GISWKGDIGGYVDSVKG;

CDR3 VH (SEQ ID NO:166): SYGSGSFYNAFDS;

CDR1 VL (SEQ ID NO:168): RASQSISSWLA;

CDR2 VL (SEQ ID NO:169): KASRLDR;

CDR3 VL (SEQ ID NO:170): LEYSSYIRT;

and where the arm to FX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:468): TSWIV;

CDR2 VH (SEQ ID NO:469): MIDPSDSFTSYSPSFQG;

CDR3 VH (SEQ ID NO:470): LHYYNSEEFDV;

CDR1 VL (SEQ ID NO:472): RASQSVSSSYLA;

CDR2 VL (SEQ ID NO:473): GQSSRTR;

CDR3 VL (SEQ ID NO:474): QQFGDSQLFT.

In one embodiment, the bispecific antibody is bimAb05-4617, wherein the arm to FIX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:148): DYAMH;

CDR2 VH (SEQ ID NO:149): GISWKGDIGGYVDSVKG;

CDR3 VH (SEQ ID NO:150): SYGSGSFYNAFDS;

CDR1 VL (SEQ ID NO:152): RASQSISSWLA;

CDR2 VL (SEQ ID NO:153): KASRLDR;

CDR3 VL (SEQ ID NO:154): LEYSSYIRT;

and where the arm to FX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:468): TSWIV;

CDR2 VH (SEQ ID NO:469): MIDPSDSFTSYSPSFQG;

CDR3 VH (SEQ ID NO:470): LHYYNSEEFDV;

CDR1 VL (SEQ ID NO:472): RASQSVSSSYLA;

CDR2 VL (SEQ ID NO:473): GQSSRTR;

CDR3 VL (SEQ ID NO:474): QQFGDSQLFT.

In one embodiment, the bispecific antibody is bimAb05-4618, wherein the arm to FIX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:156): DYAMH;

CDR2 VH (SEQ ID NO:157): GISWKGDIGGYVDSVKG;

CDR3 VH (SEQ ID NO:158): SYGSGSFYNAFDS;

CDR1 VL (SEQ ID NO:160): RASQSISSWLA;

CDR2 VL (SEQ ID NO:161): KASRLDR;

CDR3 VL (SEQ ID NO:162): LEYSSYIRT;

and where the arm to FX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:468): TSWIV;

CDR2 VH (SEQ ID NO:469): MIDPSDSFTSYSPSFQG;

CDR3 VH (SEQ ID NO:470): LHYYNSEEFDV;

CDR1 VL (SEQ ID NO:472): RASQSVSSSYLA;

CDR2 VL (SEQ ID NO:473): GQSSRTR;

CDR3 VL (SEQ ID NO:474): QQFGDSQLFT.

In one embodiment, the bispecific antibody is bimAb05-4684, wherein the arm to FIX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:52): DYAMH;

CDR2 VH (SEQ ID NO:53): GISWRGDIGGYVKSVKG;

CDR3 VH (SEQ ID NO:54): SYGSGSFYNAFDS;

CDR1 VL (SEQ ID NO:56): RASQSISSWLA;

CDR2 VL (SEQ ID NO:57): KASKLER;

CDR3 VL (SEQ ID NO:58): LEYSSYIRT;

and where the arm to FX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:500): TSWIS;

CDR2 VH (SEQ ID NO:501): MIDPSDSYTSYSPSFQG;

CDR3 VH (SEQ ID NO:502): LHYYNSEEFDV;

CDR1 VL (SEQ ID NO:504): RASQSVSSSYLA;

CDR2 VL (SEQ ID NO:505): GQSSRTR;

CDR3 VL (SEQ ID NO:506): QQFGDSQLFT.

In one embodiment, the bispecific antibody is bimAb05-4685, wherein the arm to FIX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:52): DYAMH;

CDR2 VH (SEQ ID NO:53): GISWRGDIGGYVKSVKG;

CDR3 VH (SEQ ID NO:54): SYGSGSFYNAFDS;

CDR1 VL (SEQ ID NO:56): RASQSISSWLA;

CDR2 VL (SEQ ID NO:57): KASKLER;

CDR3 VL (SEQ ID NO:58): LEYSSYIRT;

and where the arm to FX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:508): TSWIS;

CDR2 VH (SEQ ID NO:509): MIDPSDSFTSYSPSFQG;

CDR3 VH (SEQ ID NO:510): LHYYHSEEFDV;

CDR1 VL (SEQ ID NO:512): RASQSVSSSYLA;

CDR2 VL (SEQ ID NO:513): GQSSRTR;

CDR3 VL (SEQ ID NO:514): QQFGDSQLFT.

In one embodiment, the bispecific antibody is bimAb05-4686, wherein the arm to FIX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:52): DYAMH;

CDR2 VH (SEQ ID NO:53): GISWRGDIGGYVKSVKG;

CDR3 VH (SEQ ID NO:54): SYGSGSFYNAFDS;

CDR1 VL (SEQ ID NO:56): RASQSISSWLA;

CDR2 VL (SEQ ID NO:57): KASKLER;

CDR3 VL (SEQ ID NO:58): LEYSSYIRT;

and where the arm to FX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:516): TSWIS;

CDR2 VH (SEQ ID NO:517): MIDPSDSYTSYSPSFQG;

CDR3 VH (SEQ ID NO:518): LHYYHSEEFDV;

CDR1 VL (SEQ ID NO:520): RASQSVSSSYLA;

CDR2 VL (SEQ ID NO:521): GQSSRTR;

CDR3 VL (SEQ ID NO:522): QQFGDSQLFT.

In one embodiment, the bispecific antibody is bimAb05-4687, wherein the arm to FIX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:52): DYAMH;

CDR2 VH (SEQ ID NO:53): GISWRGDIGGYVKSVKG;

CDR3 VH (SEQ ID NO:54): SYGSGSFYNAFDS;

CDR1 VL (SEQ ID NO:56): RASQSISSWLA;

CDR2 VL (SEQ ID NO:57): KASKLER;

CDR3 VL (SEQ ID NO:58): LEYSSYIRT;

and where the arm to FX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:524): TSWIS;

CDR2 VH (SEQ ID NO:525): MIDPSDSYTSYSPSFQG;

CDR3 VH (SEQ ID NO:526): LHYYHSEEFDV;

CDR1 VL (SEQ ID NO:528): RASQSVSSSYLA;

CDR2 VL (SEQ ID NO:529): GQSSRTR;

CDR3 VL (SEQ ID NO:530): QQFGDSQLFT.

In one embodiment, the bispecific antibody is bimAb05-4688, wherein the arm to FIX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:52): DYAMH;

CDR2 VH (SEQ ID NO:53): GISWRGDIGGYVKSVKG;

CDR3 VH (SEQ ID NO:54): SYGSGSFYNAFDS;

CDR1 VL (SEQ ID NO:56): RASQSISSWLA;

CDR2 VL (SEQ ID NO:57): KASKLER;

CDR3 VL (SEQ ID NO:58): LEYSSYIRT;

and where the arm to FX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:532): TSWIS;

CDR2 VH (SEQ ID NO:533): MIDPSDSFTSYSPSFQG;

CDR3 VH (SEQ ID NO:534): LHYYNSEEFDV;

CDR1 VL (SEQ ID NO:536): RASQSVSSSYLA;

CDR2 VL (SEQ ID NO:537): GQSSRTR;

CDR3 VL (SEQ ID NO:538): QQFGDSQLFT.

In one embodiment, the bispecific antibody is bimAb05-4689, wherein the arm to FIX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:52): DYAMH;

CDR2 VH (SEQ ID NO:53): GISWRGDIGGYVKSVKG;

CDR3 VH (SEQ ID NO:54): SYGSGSFYNAFDS;

CDR1 VL (SEQ ID NO:56): RASQSISSWLA;

CDR2 VL (SEQ ID NO:57): KASKLER;

CDR3 VL (SEQ ID NO:58): LEYSSYIRT;

and where the arm to FX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:540): TSWIV;

CDR2 VH (SEQ ID NO:541): MIDPSDSYTSYSPSFQG;

CDR3 VH (SEQ ID NO:542): LHYYNSEEFDV;

CDR1 VL (SEQ ID NO:544): RASQSVSSSYLA;

CDR2 VL (SEQ ID NO:545): GQSSRTR;

CDR3 VL (SEQ ID NO:546): QQFGDSQLFT.

In one embodiment, the bispecific antibody is bimAb05-4690, wherein the arm to FIX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:52): DYAMH;

CDR2 VH (SEQ ID NO:53): GISWRGDIGGYVKSVKG;

CDR3 VH (SEQ ID NO:54): SYGSGSFYNAFDS;

CDR1 VL (SEQ ID NO:56): RASQSISSWLA;

CDR2 VL (SEQ ID NO:57): KASKLER;

CDR3 VL (SEQ ID NO:58): LEYSSYIRT;

and where the arm to FX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:556): TSWIV;

CDR2 VH (SEQ ID NO:557): MIDPSDSFTSYSPSFQG;

CDR3 VH (SEQ ID NO:558): LHYYNSEEFDV;

CDR1 VL (SEQ ID NO:560): RASQSVSSSYLA;

CDR2 VL (SEQ ID NO:561): GQSSRTR;

CDR3 VL (SEQ ID NO:562): QQYGDSQLFT.

In one embodiment, the bispecific antibody is bimAb05-4692, wherein the arm to FIX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:52): DYAMH;

CDR2 VH (SEQ ID NO:53): GISWRGDIGGYVKSVKG;

CDR3 VH (SEQ ID NO:54): SYGSGSFYNAFDS;

CDR1 VL (SEQ ID NO:56): RASQSISSWLA;

CDR2 VL (SEQ ID NO:57): KASKLER;

CDR3 VL (SEQ ID NO:58): LEYSSYIRT;

and where the arm to FX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:564): TSWIS;

CDR2 VH (SEQ ID NO:565): MIDPSDSFTSYSPSFQG;

CDR3 VH (SEQ ID NO:566): LHYYHSEEFDV;

CDR1 VL (SEQ ID NO:568): RASQSVSSSYLA;

CDR2 VL (SEQ ID NO:569): GQSSRTR;

CDR3 VL (SEQ ID NO:570): QQYGDSQLFT.

In one embodiment, the bispecific antibody is bimAb05-4693, wherein the arm to FIX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:52): DYAMH;

CDR2 VH (SEQ ID NO:53): GISWRGDIGGYVKSVKG;

CDR3 VH (SEQ ID NO:54): SYGSGSFYNAFDS;

CDR1 VL (SEQ ID NO:56): RASQSISSWLA;

CDR2 VL (SEQ ID NO:57): KASKLER;

CDR3 VL (SEQ ID NO:58): LEYSSYIRT;

and where the arm to FX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:572): TSWIS;

CDR2 VH (SEQ ID NO:573): MIDPSDSYTSYSPSFQG;

CDR3 VH (SEQ ID NO:574): LHYYHSEEFDV;

CDR1 VL (SEQ ID NO:576): RASQSVSSSYLA;

CDR2 VL (SEQ ID NO:577): GQSSRTR;

CDR3 VL (SEQ ID NO:578): QQYGDSQLFT.

In one embodiment, the bispecific antibody is bimAb05-4694, wherein the arm to FIX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:52): DYAMH;

CDR2 VH (SEQ ID NO:53): GISWRGDIGGYVKSVKG;

CDR3 VH (SEQ ID NO:54): SYGSGSFYNAFDS;

CDR1 VL (SEQ ID NO:56): RASQSISSWLA;

CDR2 VL (SEQ ID NO:57): KASKLER;

CDR3 VL (SEQ ID NO:58): LEYSSYIRT;

and where the arm to FX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:580): TSWIS;

CDR2 VH (SEQ ID NO:581): MIDPSDSYTSYSPSFQG;

CDR3 VH (SEQ ID NO:582): LHYYHSEEFDV;

CDR1 VL (SEQ ID NO:584): RASQSVSSSYLA;

CDR2 VL (SEQ ID NO:585): GQSSRTR;

CDR3 VL (SEQ ID NO:586): QQYGDSQLFT.

In one embodiment, the bispecific antibody is bimAb05-4695, wherein the arm to FIX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:52): DYAMH;

CDR2 VH (SEQ ID NO:53): GISWRGDIGGYVKSVKG;

CDR3 VH (SEQ ID NO:54): SYGSGSFYNAFDS;

CDR1 VL (SEQ ID NO:56): RASQSISSWLA;

CDR2 VL (SEQ ID NO:57): KASKLER;

CDR3 VL (SEQ ID NO:58): LEYSSYIRT;

and where the arm to FX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:492): TSWIS;

CDR2 VH (SEQ ID NO:493): MIDPSDSFTSYSPSFQG;

CDR3 VH (SEQ ID NO:494): LHYYNSEEFDV;

CDR1 VL (SEQ ID NO:496): RASQSVSSSYLA;

CDR2 VL (SEQ ID NO:497): GQSSRTR;

CDR3 VL (SEQ ID NO:498): QQYGDSQLFT.

In one embodiment, the bispecific antibody is bimAb05-4696, wherein the arm to FIX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:52): DYAMH;

CDR2 VH (SEQ ID NO:53): GISWRGDIGGYVKSVKG;

CDR3 VH (SEQ ID NO:54): SYGSGSFYNAFDS;

CDR1 VL (SEQ ID NO:56): RASQSISSWLA;

CDR2 VL (SEQ ID NO:57): KASKLER;

CDR3 VL (SEQ ID NO:58): LEYSSYIRT;

and where the arm to FX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:588): TSWIV;

CDR2 VH (SEQ ID NO:589): MIDPSDSYTSYSPSFQG;

CDR3 VH (SEQ ID NO:590): LHYYNSEEFDV;

CDR1 VL (SEQ ID NO:592): RASQSVSSSYLA;

CDR2 VL (SEQ ID NO:593): GQSSRTR;

CDR3 VL (SEQ ID NO:594): QQYGDSQLFT.

In one embodiment, the bispecific antibody is bimAb05-4697, wherein the arm to FIX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:52): DYAMH;

CDR2 VH (SEQ ID NO:53): GISWRGDIGGYVKSVKG;

CDR3 VH (SEQ ID NO:54): SYGSGSFYNAFDS;

CDR1 VL (SEQ ID NO:56): RASQSISSWLA;

CDR2 VL (SEQ ID NO:57): KASKLER;

CDR3 VL (SEQ ID NO:58): LEYSSYIRT;

and where the arm to FX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:596): TSWIV;

CDR2 VH (SEQ ID NO:597): MIDPSDSFTSYSPSFQG;

CDR3 VH (SEQ ID NO:598): LHYYNSEEFDV;

CDR1 VL (SEQ ID NO:600): RASQSVSSSYLA;

CDR2 VL (SEQ ID NO:601): GASSRAR;

CDR3 VL (SEQ ID NO:602): QQYGDSRLFT.

In one embodiment, the bispecific antibody is bimAb05-4698, wherein the arm to FIX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:52): DYAMH;

CDR2 VH (SEQ ID NO:53): GISWRGDIGGYVKSVKG;

CDR3 VH (SEQ ID NO:54): SYGSGSFYNAFDS;

CDR1 VL (SEQ ID NO:56): RASQSISSWLA;

CDR2 VL (SEQ ID NO:57): KASKLER;

CDR3 VL (SEQ ID NO:58): LEYSSYIRT;

and where the arm to FX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:604): TSWIS;

CDR2 VH (SEQ ID NO:605): MIDPSDSYTSYSPSFQG;

CDR3 VH (SEQ ID NO:606): LHYYNSEEFDV;

CDR1 VL (SEQ ID NO:608): RASQSVSSSYLA;

CDR2 VL (SEQ ID NO:609): GASSRAR;

CDR3 VL (SEQ ID NO:610): QQYGDSRLFT.

In one embodiment, the bispecific antibody is bimAb05-4699, wherein the arm to FIX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:52): DYAMH;

CDR2 VH (SEQ ID NO:53): GISWRGDIGGYVKSVKG;

CDR3 VH (SEQ ID NO:54): SYGSGSFYNAFDS;

CDR1 VL (SEQ ID NO:56): RASQSISSWLA;

CDR2 VL (SEQ ID NO:57): KASKLER;

CDR3 VL (SEQ ID NO:58): LEYSSYIRT;

and where the arm to FX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:612): TSWIS;

CDR2 VH (SEQ ID NO:613): MIDPSDSFTSYSPSFQG;

CDR3 VH (SEQ ID NO:614): LHYYHSEEFDV;

CDR1 VL (SEQ ID NO:616): RASQSVSSSYLA;

CDR2 VL (SEQ ID NO:617): GASSRAR;

CDR3 VL (SEQ ID NO:618): QQYGDSRLFT.

In one embodiment, the bispecific antibody is bimAb05-4700, wherein the arm to FIX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:52): DYAMH;

CDR2 VH (SEQ ID NO:53): GISWRGDIGGYVKSVKG;

CDR3 VH (SEQ ID NO:54): SYGSGSFYNAFDS;

CDR1 VL (SEQ ID NO:56): RASQSISSWLA;

CDR2 VL (SEQ ID NO:57): KASKLER;

CDR3 VL (SEQ ID NO:58): LEYSSYIRT;

and where the arm to FX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:620): TSWIS;

CDR2 VH (SEQ ID NO:621): MIDPSDSYTSYSPSFQG;

CDR3 VH (SEQ ID NO:622): LHYYHSEEFDV;

CDR1 VL (SEQ ID NO:624): RASQSVSSSYLA;

CDR2 VL (SEQ ID NO:625): GASSRAR;

CDR3 VL (SEQ ID NO:626): QQYGDSRLFT.

In one embodiment, the bispecific antibody is bimAb05-4701, wherein the arm to FIX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:52): DYAMH;

CDR2 VH (SEQ ID NO:53): GISWRGDIGGYVKSVKG;

CDR3 VH (SEQ ID NO:54): SYGSGSFYNAFDS;

CDR1 VL (SEQ ID NO:56): RASQSISSWLA;

CDR2 VL (SEQ ID NO:57): KASKLER;

CDR3 VL (SEQ ID NO:58): LEYSSYIRT;

and where the arm to FX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:628): TSWIS;

CDR2 VH (SEQ ID NO:629): MIDPSDSYTSYSPSFQG;

CDR3 VH (SEQ ID NO:630): LHYYHSEEFDV;

CDR1 VL (SEQ ID NO:632): RASQSVSSSYLA;

CDR2 VL (SEQ ID NO:633): GASSRAR;

CDR3 VL (SEQ ID NO:634): QQYGDSRLFT.

In one embodiment, the bispecific antibody is bimAb05-4702, wherein the arm to FIX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:52): DYAMH;

CDR2 VH (SEQ ID NO:53): GISWRGDIGGYVKSVKG;

CDR3 VH (SEQ ID NO:54): SYGSGSFYNAFDS;

CDR1 VL (SEQ ID NO:56): RASQSISSWLA;

CDR2 VL (SEQ ID NO:57): KASKLER;

CDR3 VL (SEQ ID NO:58): LEYSSYIRT;

and where the arm to FX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:636): TSWIS;

CDR2 VH (SEQ ID NO:637): MIDPSDSFTSYSPSFQG;

CDR3 VH (SEQ ID NO:638): LHYYNSEEFDV;

CDR1 VL (SEQ ID NO:640): RASQSVSSSYLA;

CDR2 VL (SEQ ID NO:641): GASSRAR;

CDR3 VL (SEQ ID NO:642): QQYGDSRLFT.

In one embodiment, the bispecific antibody is bimAb05-4703, wherein the arm to FIX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:52): DYAMH;

CDR2 VH (SEQ ID NO:53): GISWRGDIGGYVKSVKG;

CDR3 VH (SEQ ID NO:54): SYGSGSFYNAFDS;

CDR1 VL (SEQ ID NO:56): RASQSISSWLA;

CDR2 VL (SEQ ID NO:57): KASKLER;

CDR3 VL (SEQ ID NO:58): LEYSSYIRT;

and where the arm to FX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:644): TSWIV;

CDR2 VH (SEQ ID NO:645): MIDPSDSYTSYSPSFQG;

CDR3 VH (SEQ ID NO:646): LHYYNSEEFDV;

CDR1 VL (SEQ ID NO:648): RASQSVSSSYLA;

CDR2 VL (SEQ ID NO:649): GASSRAR;

CDR3 VL (SEQ ID NO:650): QQYGDSRLFT.

In one embodiment, the bispecific antibody is bimAb05-4704, wherein the arm to FIX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:52): DYAMH;

CDR2 VH (SEQ ID NO:53): GISWRGDIGGYVKSVKG;

CDR3 VH (SEQ ID NO:54): SYGSGSFYNAFDS;

CDR1 VL (SEQ ID NO:56): RASQSISSWLA;

CDR2 VL (SEQ ID NO:57): KASKLER;

CDR3 VL (SEQ ID NO:58): LEYSSYIRT;

and where the arm to FX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:652): TSWIV;

CDR2 VH (SEQ ID NO:653): MIDPSDSFTSYSPSFQG;

CDR3 VH (SEQ ID NO:654): LHYYNSEEFDV;

CDR1 VL (SEQ ID NO:656): RASQSVSSSYLA;

CDR2 VL (SEQ ID NO:657): GQSSRTR;

CDR3 VL (SEQ ID NO:658): QQFGDSRLFT.

In one embodiment, the bispecific antibody is bimAb05-4705, wherein the arm to FIX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:52): DYAMH;

CDR2 VH (SEQ ID NO:53): GISWRGDIGGYVKSVKG;

CDR3 VH (SEQ ID NO:54): SYGSGSFYNAFDS;

CDR1 VL (SEQ ID NO:56): RASQSISSWLA;

CDR2 VL (SEQ ID NO:57): KASKLER;

CDR3 VL (SEQ ID NO:58): LEYSSYIRT;

and where the arm to FX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:660): TSWIS;

CDR2 VH (SEQ ID NO:661): MIDPSDSYTSYSPSFQG;

CDR3 VH (SEQ ID NO:662): LHYYNSEEFDV;

CDR1 VL (SEQ ID NO:664): RASQSVSSSYLA;

CDR2 VL (SEQ ID NO:665): GQSSRTR;

CDR3 VL (SEQ ID NO:666): QQFGDSRLFT.

In one embodiment, the bispecific antibody is bimAb05-4706, wherein the arm to FIX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:52): DYAMH;

CDR2 VH (SEQ ID NO:53): GISWRGDIGGYVKSVKG;

CDR3 VH (SEQ ID NO:54): SYGSGSFYNAFDS;

CDR1 VL (SEQ ID NO:56): RASQSISSWLA;

CDR2 VL (SEQ ID NO:57): KASKLER;

CDR3 VL (SEQ ID NO:58): LEYSSYIRT;

and where the arm to FX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:668): TSWIS;

CDR2 VH (SEQ ID NO:669): MIDPSDSFTSYSPSFQG;

CDR3 VH (SEQ ID NO:670): LHYYHSEEFDV;

CDR1 VL (SEQ ID NO:672): RASQSVSSSYLA;

CDR2 VL (SEQ ID NO:673): GQSSRTR;

CDR3 VL (SEQ ID NO:674): QQFGDSRLFT.

In one embodiment, the bispecific antibody is bimAb05-4707, wherein the arm to FIX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:52): DYAMH;

CDR2 VH (SEQ ID NO:53): GISWRGDIGGYVKSVKG;

CDR3 VH (SEQ ID NO:54): SYGSGSFYNAFDS;

CDR1 VL (SEQ ID NO:56): RASQSISSWLA;

CDR2 VL (SEQ ID NO:57): KASKLER;

CDR3 VL (SEQ ID NO:58): LEYSSYIRT;

and where the arm to FX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:676): TSWIS;

CDR2 VH (SEQ ID NO:677): MIDPSDSYTSYSPSFQG;

CDR3 VH (SEQ ID NO:678): LHYYHSEEFDV;

CDR1 VL (SEQ ID NO:680): RASQSVSSSYLA;

CDR2 VL (SEQ ID NO:681): GQSSRTR;

CDR3 VL (SEQ ID NO:682): QQFGDSRLFT.

In one embodiment, the bispecific antibody is bimAb05-4708, wherein the arm to FIX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:52): DYAMH;

CDR2 VH (SEQ ID NO:53): GISWRGDIGGYVKSVKG;

CDR3 VH (SEQ ID NO:54): SYGSGSFYNAFDS;

CDR1 VL (SEQ ID NO:56): RASQSISSWLA;

CDR2 VL (SEQ ID NO:57): KASKLER;

CDR3 VL (SEQ ID NO:58): LEYSSYIRT;

and where the arm to FX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:684): TSWIS;

CDR2 VH (SEQ ID NO:685): MIDPSDSYTSYSPSFQG;

CDR3 VH (SEQ ID NO:686): LHYYHSEEFDV;

CDR1 VL (SEQ ID NO:688): RASQSVSSSYLA;

CDR2 VL (SEQ ID NO:689): GQSSRTR;

CDR3 VL (SEQ ID NO:690): QQFGDSRLFT.

In one embodiment, the bispecific antibody is bimAb05-4709, wherein the arm to FIX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:52): DYAMH;

CDR2 VH (SEQ ID NO:53): GISWRGDIGGYVKSVKG;

CDR3 VH (SEQ ID NO:54): SYGSGSFYNAFDS;

CDR1 VL (SEQ ID NO:56): RASQSISSWLA;

CDR2 VL (SEQ ID NO:57): KASKLER;

CDR3 VL (SEQ ID NO:58): LEYSSYIRT;

and where the arm to FX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:692): TSWIS;

CDR2 VH (SEQ ID NO:693): MIDPSDSFTSYSPSFQG;

CDR3 VH (SEQ ID NO:694): LHYYNSEEFDV;

CDR1 VL (SEQ ID NO:696): RASQSVSSSYLA;

CDR2 VL (SEQ ID NO:697): GQSSRTR;

CDR3 VL (SEQ ID NO:698): QQFGDSRLFT.

In one embodiment, the bispecific antibody is bimAb05-4710, wherein the arm to FIX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:52): DYAMH;

CDR2 VH (SEQ ID NO:53): GISWRGDIGGYVKSVKG;

CDR3 VH (SEQ ID NO:54): SYGSGSFYNAFDS;

CDR1 VL (SEQ ID NO:56): RASQSISSWLA;

CDR2 VL (SEQ ID NO:57): KASKLER;

CDR3 VL (SEQ ID NO:58): LEYSSYIRT;

and where the arm to FX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:700): TSWIV;

CDR2 VH (SEQ ID NO:701): MIDPSDSYTSYSPSFQG;

CDR3 VH (SEQ ID NO:702): LHYYNSEEFDV;

CDR1 VL (SEQ ID NO:704): RASQSVSSSYLA;

CDR2 VL (SEQ ID NO:705): GQSSRTR;

CDR3 VL (SEQ ID NO:706): QQFGDSRLFT.

In one embodiment, the bispecific antibody is bimAb05-4788, wherein the arm to FIX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:308): DYAMH;

CDR2 VH (SEQ ID NO:309): GISWKGDIGGYVDSVKG;

CDR3 VH (SEQ ID NO:310): SYGSGSFYNAFDS;

CDR1 VL (SEQ ID NO:312): RASQSISSWLA;

CDR2 VL (SEQ ID NO:313): KASRLDR;

CDR3 VL (SEQ ID NO:314): LEYSSYIRT;

and where the arm to FX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:468): TSWIV;

CDR2 VH (SEQ ID NO:469): MIDPSDSFTSYSPSFQG;

CDR3 VH (SEQ ID NO:470): LHYYNSEEFDV;

CDR1 VL (SEQ ID NO:472): RASQSVSSSYLA;

CDR2 VL (SEQ ID NO:473): GQSSRTR;

CDR3 VL (SEQ ID NO:474): QQFGDSQLFT.

In one embodiment, the bispecific antibody is bimAb05-4884, wherein the arm to FIX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:316): DYAMH;

CDR2 VH (SEQ ID NO:317): GISWKGDIGGYVDSVKG;

CDR3 VH (SEQ ID NO:318): SYGSGSFYNAFDS;

CDR1 VL (SEQ ID NO:320): RASQSISSWLA;

CDR2 VL (SEQ ID NO:321): KASRLDR;

CDR3 VL (SEQ ID NO:322): LEYSSYIRT;

and where the arm to FX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:468): TSWIV;

CDR2 VH (SEQ ID NO:469): MIDPSDSFTSYSPSFQG;

CDR3 VH (SEQ ID NO:470): LHYYNSEEFDV;

CDR1 VL (SEQ ID NO:472): RASQSVSSSYLA;

CDR2 VL (SEQ ID NO:473): GQSSRTR;

CDR3 VL (SEQ ID NO:474): QQFGDSQLFT.

In one embodiment, the bispecific antibody is bimAb05-4895, wherein the arm to FIX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:340): DYAMH;

CDR2 VH (SEQ ID NO:341): GISWKGDIGGYVDSVKG;

CDR3 VH (SEQ ID NO:342): SYGSGSFYNAFDS;

CDR1 VL (SEQ ID NO:344): RASQSIQSWLA;

CDR2 VL (SEQ ID NO:345): KASRLDR;

CDR3 VL (SEQ ID NO:346): LEYSSYIRT;

and where the arm to FX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:468): TSWIV;

CDR2 VH (SEQ ID NO:469): MIDPSDSFTSYSPSFQG;

CDR3 VH (SEQ ID NO:470): LHYYNSEEFDV;

CDR1 VL (SEQ ID NO:472): RASQSVSSSYLA;

CDR2 VL (SEQ ID NO:473): GQSSRTR;

CDR3 VL (SEQ ID NO:474): QQFGDSQLFT.

In one embodiment, the bispecific antibody is bimAb05-4896, wherein the arm to FIX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:324): DYAMH;

CDR2 VH (SEQ ID NO:325): GISWKGDIGGYVDSVKG;

CDR3 VH (SEQ ID NO:326): SYGSGSFYNAFDS;

CDR1 VL (SEQ ID NO:328): RASQKISSWLA;

CDR2 VL (SEQ ID NO:329): KASRLDR;

CDR3 VL (SEQ ID NO:330): LEYSSYIRT;

and where the arm to FX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:468): TSWIV;

CDR2 VH (SEQ ID NO:469): MIDPSDSFTSYSPSFQG;

CDR3 VH (SEQ ID NO:470): LHYYNSEEFDV;

CDR1 VL (SEQ ID NO:472): RASQSVSSSYLA;

CDR2 VL (SEQ ID NO:473): GQSSRTR;

CDR3 VL (SEQ ID NO:474): QQFGDSQLFT.

In one embodiment, the bispecific antibody is bimAb05-4898, wherein the arm to FIX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:332): DYAMH;

CDR2 VH (SEQ ID NO:333): GISWKGDIGGYVDSVKG;

CDR3 VH (SEQ ID NO:334): SYGSGSFYNAFDS;

CDR1 VL (SEQ ID NO:336): RASQQISSWLA;

CDR2 VL (SEQ ID NO:337): KASRLDR;

CDR3 VL (SEQ ID NO:338): LEYSSYIRT;

and where the arm to FX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:468): TSWIV;

CDR2 VH (SEQ ID NO:469): MIDPSDSFTSYSPSFQG;

CDR3 VH (SEQ ID NO:470): LHYYNSEEFDV;

CDR1 VL (SEQ ID NO:472): RASQSVSSSYLA;

CDR2 VL (SEQ ID NO:473): GQSSRTR;

CDR3 VL (SEQ ID NO:474): QQFGDSQLFT.

In one embodiment, the bispecific antibody is bimAb05-4903, wherein the arm to FIX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:356): DYAMH;

CDR2 VH (SEQ ID NO:357): GISWKGDIGGYVDSVKG;

CDR3 VH (SEQ ID NO:358): SYGSGSFYNAFDS;

CDR1 VL (SEQ ID NO:360): RASQSISSWLA;

CDR2 VL (SEQ ID NO:361): KASRLDR;

CDR3 VL (SEQ ID NO:362): LEYSSYIRT;

and where the arm to FX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:468): TSWIV;

CDR2 VH (SEQ ID NO:469): MIDPSDSFTSYSPSFQG;

CDR3 VH (SEQ ID NO:470): LHYYNSEEFDV;

CDR1 VL (SEQ ID NO:472): RASQSVSSSYLA;

CDR2 VL (SEQ ID NO:473): GQSSRTR;

CDR3 VL (SEQ ID NO:474): QQFGDSQLFT.

In one embodiment, the bispecific antibody is bimAb05-4906, wherein the arm to FIX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:348): DYAMH;

CDR2 VH (SEQ ID NO:349): GISWKGDIGGYVDSVKG;

CDR3 VH (SEQ ID NO:350): SYGSGSFYNAFDS;

CDR1 VL (SEQ ID NO:352): RASQSISSWLA;

CDR2 VL (SEQ ID NO:353): KASRLDK;

CDR3 VL (SEQ ID NO:354): LEYSSYIRT;

and where the arm to FX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:468): TSWIV;

CDR2 VH (SEQ ID NO:469): MIDPSDSFTSYSPSFQG;

CDR3 VH (SEQ ID NO:470): LHYYNSEEFDV;

CDR1 VL (SEQ ID NO:472): RASQSVSSSYLA;

CDR2 VL (SEQ ID NO:473): GQSSRTR;

CDR3 VL (SEQ ID NO:474): QQFGDSQLFT.

In one embodiment, the bispecific antibody is bimAb05-4910, wherein the arm to FIX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:364): DYAMH;

CDR2 VH (SEQ ID NO:365): GISWKGDIGGYVDSVKG;

CDR3 VH (SEQ ID NO:366): SYGSGSFYNAFDS;

CDR1 VL (SEQ ID NO:368): RASQSISSWLA;

CDR2 VL (SEQ ID NO:369): KASRLDR;

CDR3 VL (SEQ ID NO:370): LEYSSYIRT;

and where the arm to FX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:468): TSWIV;

CDR2 VH (SEQ ID NO:469): MIDPSDSFTSYSPSFQG;

CDR3 VH (SEQ ID NO:470): LHYYNSEEFDV;

CDR1 VL (SEQ ID NO:472): RASQSVSSSYLA;

CDR2 VL (SEQ ID NO:473): GQSSRTR;

CDR3 VL (SEQ ID NO:474): QQFGDSQLFT.

In one embodiment, the bispecific antibody is bimAb05-4914, wherein the arm to FIX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:372): DYAMH;

CDR2 VH (SEQ ID NO:373): GISWKGDIGGYVDSVKG;

CDR3 VH (SEQ ID NO:374): SYGSGSFYNAFDS;

CDR1 VL (SEQ ID NO:376): RASQSISSWLA;

CDR2 VL (SEQ ID NO:377): KASRLDR;

CDR3 VL (SEQ ID NO:378): LEYSSYIRT;

and where the arm to FX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:468): TSWIV;

CDR2 VH (SEQ ID NO:469): MIDPSDSFTSYSPSFQG;

CDR3 VH (SEQ ID NO:470): LHYYNSEEFDV;

CDR1 VL (SEQ ID NO:472): RASQSVSSSYLA;

CDR2 VL (SEQ ID NO:473): GQSSRTR;

CDR3 VL (SEQ ID NO:474): QQFGDSQLFT.

In one embodiment, the bispecific antibody is bimAb05-4915, wherein the arm to FIX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:380): DYAMH;

CDR2 VH (SEQ ID NO:381): GISWKGDIGGYVDSVKG;

CDR3 VH (SEQ ID NO:382): SYGSGSFYNAFDS;

CDR1 VL (SEQ ID NO:384): RASQSISSWLA;

CDR2 VL (SEQ ID NO:385): KASRLDR;

CDR3 VL (SEQ ID NO:386): LEYSSYIRT;

and where the arm to FX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:468): TSWIV;

CDR2 VH (SEQ ID NO:469): MIDPSDSFTSYSPSFQG;

CDR3 VH (SEQ ID NO:470): LHYYNSEEFDV;

CDR1 VL (SEQ ID NO:472): RASQSVSSSYLA;

CDR2 VL (SEQ ID NO:473): GQSSRTR;

CDR3 VL (SEQ ID NO:474): QQFGDSQLFT.

In one embodiment, the bispecific antibody is bimAb05-4919, wherein the arm to FIX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:388): DYAMH;

CDR2 VH (SEQ ID NO:389): GISWKGDIGGYVDSVKG;

CDR3 VH (SEQ ID NO:390): SYGSGSFYNAFDS;

CDR1 VL (SEQ ID NO:392): RASQSISSWLA;

CDR2 VL (SEQ ID NO:393): KASRLDR;

CDR3 VL (SEQ ID NO:394): LEYQSYIRT;

and where the arm to FX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:468): TSWIV;

CDR2 VH (SEQ ID NO:469): MIDPSDSFTSYSPSFQG;

CDR3 VH (SEQ ID NO:470): LHYYNSEEFDV;

CDR1 VL (SEQ ID NO:472): RASQSVSSSYLA;

CDR2 VL (SEQ ID NO:473): GQSSRTR;

CDR3 VL (SEQ ID NO:474): QQFGDSQLFT.

In one embodiment, the bispecific antibody is bimAb05-4920, wherein the arm to FIX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:404): DYAMH;

CDR2 VH (SEQ ID NO:405): GISWKGDIGGYVDSVKG;

CDR3 VH (SEQ ID NO:406): SYGSGSFYNAFDS;

CDR1 VL (SEQ ID NO:408): RASQSISSWLA;

CDR2 VL (SEQ ID NO:409): KASRLDR;

CDR3 VL (SEQ ID NO:410): LEYSSWIRT;

and where the arm to FX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:468): TSWIV;

CDR2 VH (SEQ ID NO:469): MIDPSDSFTSYSPSFQG;

CDR3 VH (SEQ ID NO:470): LHYYNSEEFDV;

CDR1 VL (SEQ ID NO:472): RASQSVSSSYLA;

CDR2 VL (SEQ ID NO:473): GQSSRTR;

CDR3 VL (SEQ ID NO:474): QQFGDSQLFT.

In one embodiment, the bispecific antibody is bimAb05-4921, wherein the arm to FIX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:396): DYAMH;

CDR2 VH (SEQ ID NO:397): GISWKGDIGGYVDSVKG;

CDR3 VH (SEQ ID NO:398): SYGSGSFYNAFDS;

CDR1 VL (SEQ ID NO:400): RASQSISSWLA;

CDR2 VL (SEQ ID NO:401): KASRLDR;

CDR3 VL (SEQ ID NO:402): LEYKSYIRT;

and where the arm to FX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:468): TSWIV;

CDR2 VH (SEQ ID NO:469): MIDPSDSFTSYSPSFQG;

CDR3 VH (SEQ ID NO:470): LHYYNSEEFDV;

CDR1 VL (SEQ ID NO:472): RASQSVSSSYLA;

CDR2 VL (SEQ ID NO:473): GQSSRTR;

CDR3 VL (SEQ ID NO:474): QQFGDSQLFT.

In one embodiment, the bispecific antibody is bimAb05-4924, wherein the arm to FIX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:420): DYAMH;

CDR2 VH (SEQ ID NO:421): GISWKGDIGGYVDSVKG;

CDR3 VH (SEQ ID NO:422): SYGSGSFYNAFDS;

CDR1 VL (SEQ ID NO:424): RASQSISSWLA;

CDR2 VL (SEQ ID NO:425): KASRLDR;

CDR3 VL (SEQ ID NO:426): LEYNSYIRT;

and where the arm to FX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:468): TSWIV;

CDR2 VH (SEQ ID NO:469): MIDPSDSFTSYSPSFQG;

CDR3 VH (SEQ ID NO:470): LHYYNSEEFDV;

CDR1 VL (SEQ ID NO:472): RASQSVSSSYLA;

CDR2 VL (SEQ ID NO:473): GQSSRTR;

CDR3 VL (SEQ ID NO:474): QQFGDSQLFT.

In one embodiment, the bispecific antibody is bimAb05-4927, wherein the arm to FIX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:412): DYAMH;

CDR2 VH (SEQ ID NO:413): GISWKGDIGGYVDSVKG;

CDR3 VH (SEQ ID NO:414): SYGSGSFYNAFDS;

CDR1 VL (SEQ ID NO:416): RASQSISSWLA;

CDR2 VL (SEQ ID NO:417): KASRLDR;

CDR3 VL (SEQ ID NO:418): LEYRSYIRT;

and where the arm to FX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:468): TSWIV;

CDR2 VH (SEQ ID NO:469): MIDPSDSFTSYSPSFQG;

CDR3 VH (SEQ ID NO:470): LHYYNSEEFDV;

CDR1 VL (SEQ ID NO:472): RASQSVSSSYLA;

CDR2 VL (SEQ ID NO:473): GQSSRTR;

CDR3 VL (SEQ ID NO:474): QQFGDSQLFT.

In one embodiment, the bispecific antibody is bimAb05-5092, wherein the arm to FIX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:428): DYAMH;

CDR2 VH (SEQ ID NO:429): GISWKGDIGGYVDSVKG;

CDR3 VH (SEQ ID NO:430): SYGSGSFYNAFDS;

CDR1 VL (SEQ ID NO:432): RASQSISSWLA;

CDR2 VL (SEQ ID NO:433): KASKLDR;

CDR3 VL (SEQ ID NO:434): LEYSSYIRT;

and where the arm to FX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:468): TSWIV;

CDR2 VH (SEQ ID NO:469): MIDPSDSFTSYSPSFQG;

CDR3 VH (SEQ ID NO:470): LHYYNSEEFDV;

CDR1 VL (SEQ ID NO:472): RASQSVSSSYLA;

CDR2 VL (SEQ ID NO:473): GQSSRTR;

CDR3 VL (SEQ ID NO:474): QQFGDSQLFT.

In one embodiment, the bispecific antibody is bimAb05-5095, wherein the arm to FIX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:132): DYAMH;

CDR2 VH (SEQ ID NO:133): GISWKGDIGGYVDSVKG;

CDR3 VH (SEQ ID NO:134): SYGSGSFYNAFDS;

CDR1 VL (SEQ ID NO:136): RASQSISSWLA;

CDR2 VL (SEQ ID NO:137): KASRLDR;

CDR3 VL (SEQ ID NO:138): LEYSSYIRT;

and where the arm to FX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:468): TSWIV;

CDR2 VH (SEQ ID NO:469): MIDPSDSFTSYSPSFQG;

CDR3 VH (SEQ ID NO:470): LHYYNSEEFDV;

CDR1 VL (SEQ ID NO:472): RASQSVSSSYLA;

CDR2 VL (SEQ ID NO:473): GQSSRTR;

CDR3 VL (SEQ ID NO:474): QQFGDSQLFT.

In one embodiment, the bispecific antibody is bimAb05-5204, wherein the arm to FIX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:436): DYAMH;

CDR2 VH (SEQ ID NO:437): GISWRGDIGGYVDSVKG;

CDR3 VH (SEQ ID NO:438): SYGSGSFYNAFDS;

CDR1 VL (SEQ ID NO:440): RASQSISSWLA;

CDR2 VL (SEQ ID NO:441): KASKLDR;

CDR3 VL (SEQ ID NO:442): LEYSSYIRT;

and where the arm to FX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:468): TSWIV;

CDR2 VH (SEQ ID NO:469): MIDPSDSFTSYSPSFQG;

CDR3 VH (SEQ ID NO:470): LHYYNSEEFDV;

CDR1 VL (SEQ ID NO:472): RASQSVSSSYLA;

CDR2 VL (SEQ ID NO:473): GQSSRTR;

CDR3 VL (SEQ ID NO:474): QQFGDSQLFT.

In one embodiment, the bispecific antibody is bimAb05-5205, wherein the arm to FIX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:444): DYAMH;

CDR2 VH (SEQ ID NO:445): GISWRGDIGGYVDSVKG;

CDR3 VH (SEQ ID NO:446): SYGSGSFYNAFDS;

CDR1 VL (SEQ ID NO:448): RASQSISSWLA;

CDR2 VL (SEQ ID NO:449): KASRLER;

CDR3 VL (SEQ ID NO:450): LEYSSYIRT;

and where the arm to FX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:468): TSWIV;

CDR2 VH (SEQ ID NO:469): MIDPSDSFTSYSPSFQG;

CDR3 VH (SEQ ID NO:470): LHYYNSEEFDV;

CDR1 VL (SEQ ID NO:472): RASQSVSSSYLA;

CDR2 VL (SEQ ID NO:473): GQSSRTR;

CDR3 VL (SEQ ID NO:474): QQFGDSQLFT.

In one embodiment, the bispecific antibody is bimAb05-5240, wherein the arm to FIX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:452): DYAMH;

CDR2 VH (SEQ ID NO:453): GISWKGDIGGYVDSVKG;

CDR3 VH (SEQ ID NO:454): SYGSGSFYNAFDS;

CDR1 VL (SEQ ID NO:456): RASQSISSWLA;

CDR2 VL (SEQ ID NO:457): KASRLDR;

CDR3 VL (SEQ ID NO:458): LEYSSYIRT;

and where the arm to FX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:468): TSWIV;

CDR2 VH (SEQ ID NO:469): MIDPSDSFTSYSPSFQG;

CDR3 VH (SEQ ID NO:470): LHYYNSEEFDV;

CDR1 VL (SEQ ID NO:472): RASQSVSSSYLA;

CDR2 VL (SEQ ID NO:473): GQSSRTR;

CDR3 VL (SEQ ID NO:474): QQFGDSQLFT.

In one embodiment, the bispecific antibody is bimAb05-5339, wherein the arm to FIX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:52): DYAMH;

CDR2 VH (SEQ ID NO:53): GISWRGDIGGYVKSVKG;

CDR3 VH (SEQ ID NO:54): SYGSGSFYNAFDS;

CDR1 VL (SEQ ID NO:56): RASQSISSWLA;

CDR2 VL (SEQ ID NO:57): KASKLER;

CDR3 VL (SEQ ID NO:58): LEYSSYIRT;

and where the arm to FX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:772): TSWIS;

CDR2 VH (SEQ ID NO:773): MIDPSDSFTSYSPSFQG;

CDR3 VH (SEQ ID NO:774): LHYYHSEEFDV;

CDR1 VL (SEQ ID NO:776): RASQSVSSSYLA;

CDR2 VL (SEQ ID NO:777): GQSSRTR;

CDR3 VL (SEQ ID NO:778): QQFGSSQLFT.

In one embodiment, the bispecific antibody is bimAb05-5340, wherein the arm to FIX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:52): DYAMH;

CDR2 VH (SEQ ID NO:53): GISWRGDIGGYVKSVKG;

CDR3 VH (SEQ ID NO:54): SYGSGSFYNAFDS;

CDR1 VL (SEQ ID NO:56): RASQSISSWLA;

CDR2 VL (SEQ ID NO:57): KASKLER;

CDR3 VL (SEQ ID NO:58): LEYSSYIRT;

and where the arm to FX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:708): TSWIV;

CDR2 VH (SEQ ID NO:709): MIDPSDSFTSYSPSFQG;

CDR3 VH (SEQ ID NO:710): LHYYNSEEFDV;

CDR1 VL (SEQ ID NO:712): RASQSVSSSYLA;

CDR2 VL (SEQ ID NO:713): GQSSRTR;

CDR3 VL (SEQ ID NO:714): QQFGSSQLFT.

In one embodiment, the bispecific antibody is bimAb05-5341, wherein the arm to FIX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:52): DYAMH;

CDR2 VH (SEQ ID NO:53): GISWRGDIGGYVKSVKG;

CDR3 VH (SEQ ID NO:54): SYGSGSFYNAFDS;

CDR1 VL (SEQ ID NO:56): RASQSISSWLA;

CDR2 VL (SEQ ID NO:57): KASKLER;

CDR3 VL (SEQ ID NO:58): LEYSSYIRT;

and where the arm to FX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:780): TSWIS;

CDR2 VH (SEQ ID NO:781): MIDPSDSYTSYSPSFQG;

CDR3 VH (SEQ ID NO:782): LHYYHSEEFDV;

CDR1 VL (SEQ ID NO:784): RASQSVSSSYLA;

CDR2 VL (SEQ ID NO:785): GQSSRTR;

CDR3 VL (SEQ ID NO:786): QQFGSSQLFT.

In one embodiment, the bispecific antibody is bimAb05-5342, wherein the arm to FIX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:52): DYAMH;

CDR2 VH (SEQ ID NO:53): GISWRGDIGGYVKSVKG;

CDR3 VH (SEQ ID NO:54): SYGSGSFYNAFDS;

CDR1 VL (SEQ ID NO:56): RASQSISSWLA;

CDR2 VL (SEQ ID NO:57): KASKLER;

CDR3 VL (SEQ ID NO:58): LEYSSYIRT;

and where the arm to FX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:764): TSWIS;

CDR2 VH (SEQ ID NO:765): MIDPSDSYTSYSPSFQG;

CDR3 VH (SEQ ID NO:766): LHYYNSEEFDV;

CDR1 VL (SEQ ID NO:768): RASQSVSSSYLA;

CDR2 VL (SEQ ID NO:769): GQSSRTR;

CDR3 VL (SEQ ID NO:770): QQFGSSQLFT.

In one embodiment, the bispecific antibody is bimAb05-5343, wherein the arm to FIX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:52): DYAMH;

CDR2 VH (SEQ ID NO:53): GISWRGDIGGYVKSVKG;

CDR3 VH (SEQ ID NO:54): SYGSGSFYNAFDS;

CDR1 VL (SEQ ID NO:56): RASQSISSWLA;

CDR2 VL (SEQ ID NO:57): KASKLER;

CDR3 VL (SEQ ID NO:58): LEYSSYIRT;

and where the arm to FX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:788): TSWIS;

CDR2 VH (SEQ ID NO:789): MIDPSDSYTSYSPSFQG;

CDR3 VH (SEQ ID NO:790): LHYYHSEEFDV;

CDR1 VL (SEQ ID NO:792): RASQSVSSSYLA;

CDR2 VL (SEQ ID NO:793): GQSSRTR;

CDR3 VL (SEQ ID NO:794): QQFGSSQLFT.

In one embodiment, the bispecific antibody is bimAb05-5344, wherein the arm to FIX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:52): DYAMH;

CDR2 VH (SEQ ID NO:53): GISWRGDIGGYVKSVKG;

CDR3 VH (SEQ ID NO:54): SYGSGSFYNAFDS;

CDR1 VL (SEQ ID NO:56): RASQSISSWLA;

CDR2 VL (SEQ ID NO:57): KASKLER;

CDR3 VL (SEQ ID NO:58): LEYSSYIRT;

and where the arm to FX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:796): TSWIS;

CDR2 VH (SEQ ID NO:797): MIDPSDSFTSYSPSFQG;

CDR3 VH (SEQ ID NO:798): LHYYNSEEFDV;

CDR1 VL (SEQ ID NO:800): RASQSVSSSYLA;

CDR2 VL (SEQ ID NO:801): GQSSRTR;

CDR3 VL (SEQ ID NO:802): QQFGSSQLFT.

In one embodiment, the bispecific antibody is bimAb05-5345, wherein the arm to FIX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:52): DYAMH;

CDR2 VH (SEQ ID NO:53): GISWRGDIGGYVKSVKG;

CDR3 VH (SEQ ID NO:54): SYGSGSFYNAFDS;

CDR1 VL (SEQ ID NO:56): RASQSISSWLA;

CDR2 VL (SEQ ID NO:57): KASKLER;

CDR3 VL (SEQ ID NO:58): LEYSSYIRT;

and where the arm to FX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:820): TSWIS;

CDR2 VH (SEQ ID NO:821): MIDPSDSYTSYSPSFQG;

CDR3 VH (SEQ ID NO:822): LHYYNSEEFDV;

CDR1 VL (SEQ ID NO:824): RASQSVSSSYLA;

CDR2 VL (SEQ ID NO:825): GQSSRTR;

CDR3 VL (SEQ ID NO:826): QQFGESQLFT.

In one embodiment, the bispecific antibody is bimAb05-5346, wherein the arm to FIX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:52): DYAMH;

CDR2 VH (SEQ ID NO:53): GISWRGDIGGYVKSVKG;

CDR3 VH (SEQ ID NO:54): SYGSGSFYNAFDS;

CDR1 VL (SEQ ID NO:56): RASQSISSWLA;

CDR2 VL (SEQ ID NO:57): KASKLER;

CDR3 VL (SEQ ID NO:58): LEYSSYIRT;

and where the arm to FX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:804): TSWIV;

CDR2 VH (SEQ ID NO:805): MIDPSDSYTSYSPSFQG;

CDR3 VH (SEQ ID NO:806): LHYYNSEEFDV;

CDR1 VL (SEQ ID NO:808): RASQSVSSSYLA;

CDR2 VL (SEQ ID NO:809): GQSSRTR;

CDR3 VL (SEQ ID NO:810): QQFGSSQLFT.

In one embodiment, the bispecific antibody is bimAb05-5347, wherein the arm to FIX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:52): DYAMH;

CDR2 VH (SEQ ID NO:53): GISWRGDIGGYVKSVKG;

CDR3 VH (SEQ ID NO:54): SYGSGSFYNAFDS;

CDR1 VL (SEQ ID NO:56): RASQSISSWLA;

CDR2 VL (SEQ ID NO:57): KASKLER;

CDR3 VL (SEQ ID NO:58): LEYSSYIRT;

and where the arm to FX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:828): TSWIS;

CDR2 VH (SEQ ID NO:829): MIDPSDSFTSYSPSFQG;

CDR3 VH (SEQ ID NO:830): LHYYHSEEFDV;

CDR1 VL (SEQ ID NO:832): RASQSVSSSYLA;

CDR2 VL (SEQ ID NO:833): GQSSRTR;

CDR3 VL (SEQ ID NO:834): QQFGESQLFT.

In one embodiment, the bispecific antibody is bimAb05-5348, wherein the arm to FIX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:52): DYAMH;

CDR2 VH (SEQ ID NO:53): GISWRGDIGGYVKSVKG;

CDR3 VH (SEQ ID NO:54): SYGSGSFYNAFDS;

CDR1 VL (SEQ ID NO:56): RASQSISSWLA;

CDR2 VL (SEQ ID NO:57): KASKLER;

CDR3 VL (SEQ ID NO:58): LEYSSYIRT;

and where the arm to FX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:812): TSWIV;

CDR2 VH (SEQ ID NO:813): MIDPSDSYTSYSPSFQG;

CDR3 VH (SEQ ID NO:814): LHYYNSEEFDV;

CDR1 VL (SEQ ID NO:816): RASQSVSSSYLA;

CDR2 VL (SEQ ID NO:817): GQSSRTR;

CDR3 VL (SEQ ID NO:818): QQFGSSQLFT.

In one embodiment, the bispecific antibody is bimAb05-5349, wherein the arm to FIX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:52): DYAMH;

CDR2 VH (SEQ ID NO:53): GISWRGDIGGYVKSVKG;

CDR3 VH (SEQ ID NO:54): SYGSGSFYNAFDS;

CDR1 VL (SEQ ID NO:56): RASQSISSWLA;

CDR2 VL (SEQ ID NO:57): KASKLER;

CDR3 VL (SEQ ID NO:58): LEYSSYIRT;

and where the arm to FX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:836): TSWIS;

CDR2 VH (SEQ ID NO:837): MIDPSDSYTSYSPSFQG;

CDR3 VH (SEQ ID NO:838): LHYYHSEEFDV;

CDR1 VL (SEQ ID NO:840): RASQSVSSSYLA;

CDR2 VL (SEQ ID NO:841): GQSSRTR;

CDR3 VL (SEQ ID NO:842): QQFGESQLFT.

In one embodiment, the bispecific antibody is bimAb05-5350, wherein the arm to FIX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:52): DYAMH;

CDR2 VH (SEQ ID NO:53): GISWRGDIGGYVKSVKG;

CDR3 VH (SEQ ID NO:54): SYGSGSFYNAFDS;

CDR1 VL (SEQ ID NO:56): RASQSISSWLA;

CDR2 VL (SEQ ID NO:57): KASKLER;

CDR3 VL (SEQ ID NO:58): LEYSSYIRT;

and where the arm to FX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:716): TSWIV;

CDR2 VH (SEQ ID NO:717): MIDPSDSFTSYSPSFQG;

CDR3 VH (SEQ ID NO:718): LHYYNSEEFDV;

CDR1 VL (SEQ ID NO:720): RASQSVSSSYLA;

CDR2 VL (SEQ ID NO:721): GQSSRTR;

CDR3 VL (SEQ ID NO:722): QQFGESQLFT.

In one embodiment, the bispecific antibody is bimAb05-5351, wherein the arm to FIX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:52): DYAMH;

CDR2 VH (SEQ ID NO:53): GISWRGDIGGYVKSVKG;

CDR3 VH (SEQ ID NO:54): SYGSGSFYNAFDS;

CDR1 VL (SEQ ID NO:56): RASQSISSWLA;

CDR2 VL (SEQ ID NO:57): KASKLER;

CDR3 VL (SEQ ID NO:58): LEYSSYIRT;

and where the arm to FX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:844): TSWIS;

CDR2 VH (SEQ ID NO:845): MIDPSDSYTSYSPSFQG;

CDR3 VH (SEQ ID NO:846): LHYYHSEEFDV;

CDR1 VL (SEQ ID NO:848): RASQSVSSSYLA;

CDR2 VL (SEQ ID NO:849): GQSSRTR;

CDR3 VL (SEQ ID NO:850): QQFGESQLFT.

In one embodiment, the bispecific antibody is bimAb05-5352, wherein the arm to FIX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:52): DYAMH;

CDR2 VH (SEQ ID NO:53): GISWRGDIGGYVKSVKG;

CDR3 VH (SEQ ID NO:54): SYGSGSFYNAFDS;

CDR1 VL (SEQ ID NO:56): RASQSISSWLA;

CDR2 VL (SEQ ID NO:57): KASKLER;

CDR3 VL (SEQ ID NO:58): LEYSSYIRT;

and where the arm to FX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:852): TSWIS;

CDR2 VH (SEQ ID NO:853): MIDPSDSFTSYSPSFQG;

CDR3 VH (SEQ ID NO:854): LHYYNSEEFDV;

CDR1 VL (SEQ ID NO:856): RASQSVSSSYLA;

CDR2 VL (SEQ ID NO:857): GQSSRTR;

CDR3 VL (SEQ ID NO:858): QQFGESQLFT.

In one embodiment, the bispecific antibody is bimAb05-5353, wherein the arm to FIX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:52): DYAMH;

CDR2 VH (SEQ ID NO:53): GISWRGDIGGYVKSVKG;

CDR3 VH (SEQ ID NO:54): SYGSGSFYNAFDS;

CDR1 VL (SEQ ID NO:56): RASQSISSWLA;

CDR2 VL (SEQ ID NO:57): KASKLER;

CDR3 VL (SEQ ID NO:58): LEYSSYIRT;

and where the arm to FX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:876): TSWIS;

CDR2 VH (SEQ ID NO:877): MIDPSDSYTSYSPSFQG;

CDR3 VH (SEQ ID NO:878): LHYYNSEEFDV;

CDR1 VL (SEQ ID NO:880): RASQSVSSSYLA;

CDR2 VL (SEQ ID NO:881): GQSSRTR;

CDR3 VL (SEQ ID NO:882): QQFGNSQLFT.

In one embodiment, the bispecific antibody is bimAb05-5354, wherein the arm to FIX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:52): DYAMH;

CDR2 VH (SEQ ID NO:53): GISWRGDIGGYVKSVKG;

CDR3 VH (SEQ ID NO:54): SYGSGSFYNAFDS;

CDR1 VL (SEQ ID NO:56): RASQSISSWLA;

CDR2 VL (SEQ ID NO:57): KASKLER;

CDR3 VL (SEQ ID NO:58): LEYSSYIRT;

and where the arm to FX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:860): TSWIV;

CDR2 VH (SEQ ID NO:861): MIDPSDSYTSYSPSFQG;

CDR3 VH (SEQ ID NO:862): LHYYNSEEFDV;

CDR1 VL (SEQ ID NO:864): RASQSVSSSYLA;

CDR2 VL (SEQ ID NO:865): GQSSRTR;

CDR3 VL (SEQ ID NO:866): QQFGESQLFT.

In one embodiment, the bispecific antibody is bimAb05-5355, wherein the arm to FIX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:52): DYAMH;

CDR2 VH (SEQ ID NO:53): GISWRGDIGGYVKSVKG;

CDR3 VH (SEQ ID NO:54): SYGSGSFYNAFDS;

CDR1 VL (SEQ ID NO:56): RASQSISSWLA;

CDR2 VL (SEQ ID NO:57): KASKLER;

CDR3 VL (SEQ ID NO:58): LEYSSYIRT;

and where the arm to FX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:884): TSWIS;

CDR2 VH (SEQ ID NO:885): MIDPSDSFTSYSPSFQG;

CDR3 VH (SEQ ID NO:886): LHYYHSEEFDV;

CDR1 VL (SEQ ID NO:888): RASQSVSSSYLA;

CDR2 VL (SEQ ID NO:889): GQSSRTR;

CDR3 VL (SEQ ID NO:890): QQFGNSQLFT.

In one embodiment, the bispecific antibody is bimAb05-5356, wherein the arm to FIX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:52): DYAMH;

CDR2 VH (SEQ ID NO:53): GISWRGDIGGYVKSVKG;

CDR3 VH (SEQ ID NO:54): SYGSGSFYNAFDS;

CDR1 VL (SEQ ID NO:56): RASQSISSWLA;

CDR2 VL (SEQ ID NO:57): KASKLER;

CDR3 VL (SEQ ID NO:58): LEYSSYIRT;

and where the arm to FX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:868): TSWIV;

CDR2 VH (SEQ ID NO:869): MIDPSDSYTSYSPSFQG;

CDR3 VH (SEQ ID NO:870): LHYYNSEEFDV;

CDR1 VL (SEQ ID NO:872): RASQSVSSSYLA;

CDR2 VL (SEQ ID NO:873): GQSSRTR;

CDR3 VL (SEQ ID NO:874): QQFGESQLFT.

In one embodiment, the bispecific antibody is bimAb05-5357, wherein the arm to FIX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:52): DYAMH;

CDR2 VH (SEQ ID NO:53): GISWRGDIGGYVKSVKG;

CDR3 VH (SEQ ID NO:54): SYGSGSFYNAFDS;

CDR1 VL (SEQ ID NO:56): RASQSISSWLA;

CDR2 VL (SEQ ID NO:57): KASKLER;

CDR3 VL (SEQ ID NO:58): LEYSSYIRT;

and where the arm to FX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:892): TSWIS;

CDR2 VH (SEQ ID NO:893): MIDPSDSYTSYSPSFQG;

CDR3 VH (SEQ ID NO:894): LHYYHSEEFDV;

CDR1 VL (SEQ ID NO:896): RASQSVSSSYLA;

CDR2 VL (SEQ ID NO:897): GQSSRTR;

CDR3 VL (SEQ ID NO:898): QQFGNSQLFT.

In one embodiment, the bispecific antibody is bimAb05-5358, wherein the arm to FIX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:52): DYAMH;

CDR2 VH (SEQ ID NO:53): GISWRGDIGGYVKSVKG;

CDR3 VH (SEQ ID NO:54): SYGSGSFYNAFDS;

CDR1 VL (SEQ ID NO:56): RASQSISSWLA;

CDR2 VL (SEQ ID NO:57): KASKLER;

CDR3 VL (SEQ ID NO:58): LEYSSYIRT;

and where the arm to FX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:724): TSWIV;

CDR2 VH (SEQ ID NO:725): MIDPSDSFTSYSPSFQG;

CDR3 VH (SEQ ID NO:726): LHYYNSEEFDV;

CDR1 VL (SEQ ID NO:728): RASQSVSSSYLA;

CDR2 VL (SEQ ID NO:729): GQSSRTR;

CDR3 VL (SEQ ID NO:730): QQFGNSQLFT.

In one embodiment, the bispecific antibody is bimAb05-5359, wherein the arm to FIX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:52): DYAMH;

CDR2 VH (SEQ ID NO:53): GISWRGDIGGYVKSVKG;

CDR3 VH (SEQ ID NO:54): SYGSGSFYNAFDS;

CDR1 VL (SEQ ID NO:56): RASQSISSWLA;

CDR2 VL (SEQ ID NO:57): KASKLER;

CDR3 VL (SEQ ID NO:58): LEYSSYIRT;

and where the arm to FX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:900): TSWIS;

CDR2 VH (SEQ ID NO:901): MIDPSDSYTSYSPSFQG;

CDR3 VH (SEQ ID NO:902): LHYYHSEEFDV;

CDR1 VL (SEQ ID NO:904): RASQSVSSSYLA;

CDR2 VL (SEQ ID NO:905): GQSSRTR;

CDR3 VL (SEQ ID NO:906): QQFGNSQLFT.

In one embodiment, the bispecific antibody is bimAb05-5361, wherein the arm to FIX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:52): DYAMH;

CDR2 VH (SEQ ID NO:53): GISWRGDIGGYVKSVKG;

CDR3 VH (SEQ ID NO:54): SYGSGSFYNAFDS;

CDR1 VL (SEQ ID NO:56): RASQSISSWLA;

CDR2 VL (SEQ ID NO:57): KASKLER;

CDR3 VL (SEQ ID NO:58): LEYSSYIRT;

and where the arm to FX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:924): TSWIV;

CDR2 VH (SEQ ID NO:925): MIDPSDSYTSYSPSFQG;

CDR3 VH (SEQ ID NO:926): LHYYNSEEFDV;

CDR1 VL (SEQ ID NO:928): RASQSVSSSYLA;

CDR2 VL (SEQ ID NO:929): GQSSRTR;

CDR3 VL (SEQ ID NO:930): QQFGNSQLFT.

In one embodiment, the bispecific antibody is bimAb05-5362, wherein the arm to FIX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:52): DYAMH;

CDR2 VH (SEQ ID NO:53): GISWRGDIGGYVKSVKG;

CDR3 VH (SEQ ID NO:54): SYGSGSFYNAFDS;

CDR1 VL (SEQ ID NO:56): RASQSISSWLA;

CDR2 VL (SEQ ID NO:57): KASKLER;

CDR3 VL (SEQ ID NO:58): LEYSSYIRT;

and where the arm to FX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:908): TSWIS;

CDR2 VH (SEQ ID NO:909): MIDPSDSFTSYSPSFQG;

CDR3 VH (SEQ ID NO:910): LHYYNSEEFDV;

CDR1 VL (SEQ ID NO:912): RASQSVSSSYLA;

CDR2 VL (SEQ ID NO:913): GQSSRTR;

CDR3 VL (SEQ ID NO:914): QQFGNSQLFT.

In one embodiment, the bispecific antibody is bimAb05-5363, wherein the arm to FIX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:52): DYAMH;

CDR2 VH (SEQ ID NO:53): GISWRGDIGGYVKSVKG;

CDR3 VH (SEQ ID NO:54): SYGSGSFYNAFDS;

CDR1 VL (SEQ ID NO:56): RASQSISSWLA;

CDR2 VL (SEQ ID NO:57): KASKLER;

CDR3 VL (SEQ ID NO:58): LEYSSYIRT;

and where the arm to FX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:732): TSWIV;

CDR2 VH (SEQ ID NO:733): MIDPSDSFTSYSPSFQG;

CDR3 VH (SEQ ID NO:734): LHYYNSEEFDV;

CDR1 VL (SEQ ID NO:736): RASQSVSSSYLA;

CDR2 VL (SEQ ID NO:737): GQSSRTR;

CDR3 VL (SEQ ID NO:738): QQFGQSQLFT.

In one embodiment, the bispecific antibody is bimAb05-5364, wherein the arm to FIX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:52): DYAMH;

CDR2 VH (SEQ ID NO:53): GISWRGDIGGYVKSVKG;

CDR3 VH (SEQ ID NO:54): SYGSGSFYNAFDS;

CDR1 VL (SEQ ID NO:56): RASQSISSWLA;

CDR2 VL (SEQ ID NO:57): KASKLER;

CDR3 VL (SEQ ID NO:58): LEYSSYIRT;

and where the arm to FX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:916): TSWIV;

CDR2 VH (SEQ ID NO:917): MIDPSDSYTSYSPSFQG;

CDR3 VH (SEQ ID NO:918): LHYYNSEEFDV;

CDR1 VL (SEQ ID NO:920): RASQSVSSSYLA;

CDR2 VL (SEQ ID NO:921): GQSSRTR;

CDR3 VL (SEQ ID NO:922): QQFGNSQLFT.

In one embodiment, the bispecific antibody is bimAb05-5365, wherein the arm to FIX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:52): DYAMH;

CDR2 VH (SEQ ID NO:53): GISWRGDIGGYVKSVKG;

CDR3 VH (SEQ ID NO:54): SYGSGSFYNAFDS;

CDR1 VL (SEQ ID NO:56): RASQSISSWLA;

CDR2 VL (SEQ ID NO:57): KASKLER;

CDR3 VL (SEQ ID NO:58): LEYSSYIRT;

and where the arm to FX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:932): TSWIS;

CDR2 VH (SEQ ID NO:933): MIDPSDSYTSYSPSFQG;

CDR3 VH (SEQ ID NO:934): LHYYNSEEFDV;

CDR1 VL (SEQ ID NO:936): RASQSVSSSYLA;

CDR2 VL (SEQ ID NO:937): GQSSRTR;

CDR3 VL (SEQ ID NO:938): QQFGQSQLFT.

In one embodiment, the bispecific antibody is bimAb05-5366, wherein the arm to FIX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:52): DYAMH;

CDR2 VH (SEQ ID NO:53): GISWRGDIGGYVKSVKG;

CDR3 VH (SEQ ID NO:54): SYGSGSFYNAFDS;

CDR1 VL (SEQ ID NO:56): RASQSISSWLA;

CDR2 VL (SEQ ID NO:57): KASKLER;

CDR3 VL (SEQ ID NO:58): LEYSSYIRT;

and where the arm to FX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:940): TSWIS;

CDR2 VH (SEQ ID NO:941): MIDPSDSFTSYSPSFQG;

CDR3 VH (SEQ ID NO:942): LHYYHSEEFDV;

CDR1 VL (SEQ ID NO:944): RASQSVSSSYLA;

CDR2 VL (SEQ ID NO:945): GQSSRTR;

CDR3 VL (SEQ ID NO:946): QQFGQSQLFT.

In one embodiment, the bispecific antibody is bimAb05-5367, wherein the arm to FIX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:52): DYAMH;

CDR2 VH (SEQ ID NO:53): GISWRGDIGGYVKSVKG;

CDR3 VH (SEQ ID NO:54): SYGSGSFYNAFDS;

CDR1 VL (SEQ ID NO:56): RASQSISSWLA;

CDR2 VL (SEQ ID NO:57): KASKLER;

CDR3 VL (SEQ ID NO:58): LEYSSYIRT;

and where the arm to FX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:964): TSWIV;

CDR2 VH (SEQ ID NO:965): MIDPSDSYTSYSPSFQG;

CDR3 VH (SEQ ID NO:966): LHYYNSEEFDV;

CDR1 VL (SEQ ID NO:968): RASQSVSSSYLA;

CDR2 VL (SEQ ID NO:969): GQSSRTR;

CDR3 VL (SEQ ID NO:970): QQFGQSQLFT.

In one embodiment, the bispecific antibody is bimAb05-5369, wherein the arm to FIX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:52): DYAMH;

CDR2 VH (SEQ ID NO:53): GISWRGDIGGYVKSVKG;

CDR3 VH (SEQ ID NO:54): SYGSGSFYNAFDS;

CDR1 VL (SEQ ID NO:56): RASQSISSWLA;

CDR2 VL (SEQ ID NO:57): KASKLER;

CDR3 VL (SEQ ID NO:58): LEYSSYIRT;

and where the arm to FX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:972): TSWIV;

CDR2 VH (SEQ ID NO:973): MIDPSDSYTSYSPSFQG;

CDR3 VH (SEQ ID NO:974): LHYYNSEEFDV;

CDR1 VL (SEQ ID NO:976): RASQSVSSSYLA;

CDR2 VL (SEQ ID NO:977): GQSSRTR;

CDR3 VL (SEQ ID NO:978): QQFGQSQLFT.

In one embodiment, the bispecific antibody is bimAb05-5370, wherein the arm to FIX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:52): DYAMH;

CDR2 VH (SEQ ID NO:53): GISWRGDIGGYVKSVKG;

CDR3 VH (SEQ ID NO:54): SYGSGSFYNAFDS;

CDR1 VL (SEQ ID NO:56): RASQSISSWLA;

CDR2 VL (SEQ ID NO:57): KASKLER;

CDR3 VL (SEQ ID NO:58): LEYSSYIRT;

and where the arm to FX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:948): TSWIS;

CDR2 VH (SEQ ID NO:949): MIDPSDSYTSYSPSFQG;

CDR3 VH (SEQ ID NO:950): LHYYHSEEFDV;

CDR1 VL (SEQ ID NO:952): RASQSVSSSYLA;

CDR2 VL (SEQ ID NO:953): GQSSRTR;

CDR3 VL (SEQ ID NO:954): QQFGQSQLFT.

In one embodiment, the bispecific antibody is bimAb05-5371, wherein the arm to FIX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:52): DYAMH;

CDR2 VH (SEQ ID NO:53): GISWRGDIGGYVKSVKG;

CDR3 VH (SEQ ID NO:54): SYGSGSFYNAFDS;

CDR1 VL (SEQ ID NO:56): RASQSISSWLA;

CDR2 VL (SEQ ID NO:57): KASKLER;

CDR3 VL (SEQ ID NO:58): LEYSSYIRT;

and where the arm to FX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:740): TSWIV;

CDR2 VH (SEQ ID NO:741): MIDPSDSFTSYSPSFQG;

CDR3 VH (SEQ ID NO:742): LHYYNSEEFDV;

CDR1 VL (SEQ ID NO:744): RASQSVSSSYLA;

CDR2 VL (SEQ ID NO:745): GQSSRTR;

CDR3 VL (SEQ ID NO:746): QQFGDAQLFT.

In one embodiment, the bispecific antibody is bimAb05-5372, wherein the arm to FIX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:52): DYAMH;

CDR2 VH (SEQ ID NO:53): GISWRGDIGGYVKSVKG;

CDR3 VH (SEQ ID NO:54): SYGSGSFYNAFDS;

CDR1 VL (SEQ ID NO:56): RASQSISSWLA;

CDR2 VL (SEQ ID NO:57): KASKLER;

CDR3 VL (SEQ ID NO:58): LEYSSYIRT;

and where the arm to FX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:956): TSWIS;

CDR2 VH (SEQ ID NO:957): MIDPSDSFTSYSPSFQG;

CDR3 VH (SEQ ID NO:958): LHYYNSEEFDV;

CDR1 VL (SEQ ID NO:960): RASQSVSSSYLA;

CDR2 VL (SEQ ID NO:961): GQSSRTR;

CDR3 VL (SEQ ID NO:962): QQFGQSQLFT.

In one embodiment, the bispecific antibody is bimAb05-5373, wherein the arm to FIX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:52): DYAMH;

CDR2 VH (SEQ ID NO:53): GISWRGDIGGYVKSVKG;

CDR3 VH (SEQ ID NO:54): SYGSGSFYNAFDS;

CDR1 VL (SEQ ID NO:56): RASQSISSWLA;

CDR2 VL (SEQ ID NO:57): KASKLER;

CDR3 VL (SEQ ID NO:58): LEYSSYIRT;

and where the arm to FX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:980): TSWIS;

CDR2 VH (SEQ ID NO:981): MIDPSDSYTSYSPSFQG;

CDR3 VH (SEQ ID NO:982): LHYYNSEEFDV;

CDR1 VL (SEQ ID NO:984): RASQSVSSSYLA;

CDR2 VL (SEQ ID NO:985): GQSSRTR;

CDR3 VL (SEQ ID NO:986): QQFGDAQLFT.

In one embodiment, the bispecific antibody is bimAb05-5374, wherein the arm to FIX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:52): DYAMH;

CDR2 VH (SEQ ID NO:53): GISWRGDIGGYVKSVKG;

CDR3 VH (SEQ ID NO:54): SYGSGSFYNAFDS;

CDR1 VL (SEQ ID NO:56): RASQSISSWLA;

CDR2 VL (SEQ ID NO:57): KASKLER;

CDR3 VL (SEQ ID NO:58): LEYSSYIRT;

and where the arm to FX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:988): TSWIS;

CDR2 VH (SEQ ID NO:989): MIDPSDSFTSYSPSFQG;

CDR3 VH (SEQ ID NO:990): LHYYHSEEFDV;

CDR1 VL (SEQ ID NO:992): RASQSVSSSYLA;

CDR2 VL (SEQ ID NO:993): GQSSRTR;

CDR3 VL (SEQ ID NO:994): QQFGDAQLFT.

In one embodiment, the bispecific antibody is bimAb05-5375, wherein the arm to FIX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:52): DYAMH;

CDR2 VH (SEQ ID NO:53): GISWRGDIGGYVKSVKG;

CDR3 VH (SEQ ID NO:54): SYGSGSFYNAFDS;

CDR1 VL (SEQ ID NO:56): RASQSISSWLA;

CDR2 VL (SEQ ID NO:57): KASKLER;

CDR3 VL (SEQ ID NO:58): LEYSSYIRT;

and where the arm to FX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:1012): TSWIV;

CDR2 VH (SEQ ID NO:1013): MIDPSDSYTSYSPSFQG;

CDR3 VH (SEQ ID NO:1014): LHYYNSEEFDV;

CDR1 VL (SEQ ID NO:1016): RASQSVSSSYLA;

CDR2 VL (SEQ ID NO:1017): GQSSRTR;

CDR3 VL (SEQ ID NO:1018): QQFGDAQLFT.

In one embodiment, the bispecific antibody is bimAb05-5377, wherein the arm to FIX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:52): DYAMH;

CDR2 VH (SEQ ID NO:53): GISWRGDIGGYVKSVKG;

CDR3 VH (SEQ ID NO:54): SYGSGSFYNAFDS;

CDR1 VL (SEQ ID NO:56): RASQSISSWLA;

CDR2 VL (SEQ ID NO:57): KASKLER;

CDR3 VL (SEQ ID NO:58): LEYSSYIRT;

and where the arm to FX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:1020): TSWIV;

CDR2 VH (SEQ ID NO:1021): MIDPSDSYTSYSPSFQG;

CDR3 VH (SEQ ID NO:1022): LHYYNSEEFDV;

CDR1 VL (SEQ ID NO:1024): RASQSVSSSYLA;

CDR2 VL (SEQ ID NO:1025): GQSSRTR;

CDR3 VL (SEQ ID NO:1026): QQFGDAQLFT.

In one embodiment, the bispecific antibody is bimAb05-5378, wherein the arm to FIX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:52): DYAMH;

CDR2 VH (SEQ ID NO:53): GISWRGDIGGYVKSVKG;

CDR3 VH (SEQ ID NO:54): SYGSGSFYNAFDS;

CDR1 VL (SEQ ID NO:56): RASQSISSWLA;

CDR2 VL (SEQ ID NO:57): KASKLER;

CDR3 VL (SEQ ID NO:58): LEYSSYIRT;

and where the arm to FX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:996): TSWIS;

CDR2 VH (SEQ ID NO:997): MIDPSDSYTSYSPSFQG;

CDR3 VH (SEQ ID NO:998): LHYYHSEEFDV;

CDR1 VL (SEQ ID NO:1000): RASQSVSSSYLA;

CDR2 VL (SEQ ID NO:1001): GQSSRTR;

CDR3 VL (SEQ ID NO:1002): QQFGDAQLFT.

In one embodiment, the bispecific antibody is bimAb05-5379, wherein the arm to FIX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:52): DYAMH;

CDR2 VH (SEQ ID NO:53): GISWRGDIGGYVKSVKG;

CDR3 VH (SEQ ID NO:54): SYGSGSFYNAFDS;

CDR1 VL (SEQ ID NO:56): RASQSISSWLA;

CDR2 VL (SEQ ID NO:57): KASKLER;

CDR3 VL (SEQ ID NO:58): LEYSSYIRT;

and where the arm to FX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:748): TSWIV;

CDR2 VH (SEQ ID NO:749): MIDPSDSFTSYSPSFQG;

CDR3 VH (SEQ ID NO:750): LHYYNSEEFDV;

CDR1 VL (SEQ ID NO:752): RASQSVSSSYLA;

CDR2 VL (SEQ ID NO:753): GQSSRTR;

CDR3 VL (SEQ ID NO:754): QQFGDTQLFT.

In one embodiment, the bispecific antibody is bimAb05-5380, wherein the arm to FIX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:52): DYAMH;

CDR2 VH (SEQ ID NO:53): GISWRGDIGGYVKSVKG;

CDR3 VH (SEQ ID NO:54): SYGSGSFYNAFDS;

CDR1 VL (SEQ ID NO:56): RASQSISSWLA;

CDR2 VL (SEQ ID NO:57): KASKLER;

CDR3 VL (SEQ ID NO:58): LEYSSYIRT;

and where the arm to FX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:1004): TSWIS;

CDR2 VH (SEQ ID NO:1005): MIDPSDSFTSYSPSFQG;

CDR3 VH (SEQ ID NO:1006): LHYYNSEEFDV;

CDR1 VL (SEQ ID NO:1008): RASQSVSSSYLA;

CDR2 VL (SEQ ID NO:1009): GQSSRTR;

CDR3 VL (SEQ ID NO:1010): QQFGDAQLFT.

In one embodiment, the bispecific antibody is bimAb05-5381, wherein the arm to FIX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:52): DYAMH;

CDR2 VH (SEQ ID NO:53): GISWRGDIGGYVKSVKG;

CDR3 VH (SEQ ID NO:54): SYGSGSFYNAFDS;

CDR1 VL (SEQ ID NO:56): RASQSISSWLA;

CDR2 VL (SEQ ID NO:57): KASKLER;

CDR3 VL (SEQ ID NO:58): LEYSSYIRT;

and where the arm to FX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:1028): TSWIS;

CDR2 VH (SEQ ID NO:1029): MIDPSDSYTSYSPSFQG;

CDR3 VH (SEQ ID NO:1030): LHYYNSEEFDV;

CDR1 VL (SEQ ID NO:1032): RASQSVSSSYLA;

CDR2 VL (SEQ ID NO:1033): GQSSRTR;

CDR3 VL (SEQ ID NO:1034): QQFGDTQLFT.

In one embodiment, the bispecific antibody is bimAb05-5383, wherein the arm to FIX(a) contains the following CDR sequences:

VH CDR1(SEQ ID NO:52): DYAMH;

CDR2 VH (SEQ ID NO:53): GISWRGDIGGYVKSVKG;

CDR3 VH (SEQ ID NO:54): SYGSGSFYNAFDS;

CDR1 VL (SEQ ID NO:56): RASQSISSWLA;

CDR2 VL (SEQ ID NO:57): KASKLER;

CDR3 VL (SEQ ID NO:58): LEYSSYIRT;

and where the arm to FX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:1052): TSWIS;

CDR2 VH (SEQ ID NO:1053): MIDPSDSYTSYSPSFQG;

CDR3 VH (SEQ ID NO:1054): LHYYHSEEFDV;

CDR1 VL (SEQ ID NO:1056): RASQSVSSSYLA;

CDR2 VL (SEQ ID NO:1057): GQSSRTR;

CDR3 VL (SEQ ID NO:1058): QQFGDTQLFT.

In one embodiment, the bispecific antibody is bimAb05-5384, wherein the arm to FIX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:52): DYAMH;

CDR2 VH (SEQ ID NO:53): GISWRGDIGGYVKSVKG;

CDR3 VH (SEQ ID NO:54): SYGSGSFYNAFDS;

CDR1 VL (SEQ ID NO:56): RASQSISSWLA;

CDR2 VL (SEQ ID NO:57): KASKLER;

CDR3 VL (SEQ ID NO:58): LEYSSYIRT;

and where the arm to FX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:1036): TSWIS;

CDR2 VH (SEQ ID NO:1037): MIDPSDSFTSYSPSFQG;

CDR3 VH (SEQ ID NO:1038): LHYYHSEEFDV;

CDR1 VL (SEQ ID NO:1040): RASQSVSSSYLA;

CDR2 VL (SEQ ID NO:1041): GQSSRTR;

CDR3 VL (SEQ ID NO:1042): QQFGDTQLFT.

In one embodiment, the bispecific antibody is bimAb05-5385, wherein the arm to FIX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:52): DYAMH;

CDR2 VH (SEQ ID NO:53): GISWRGDIGGYVKSVKG;

CDR3 VH (SEQ ID NO:54): SYGSGSFYNAFDS;

CDR1 VL (SEQ ID NO:56): RASQSISSWLA;

CDR2 VL (SEQ ID NO:57): KASKLER;

CDR3 VL (SEQ ID NO:58): LEYSSYIRT;

and where the arm to FX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:1060): TSWIS;

CDR2 VH (SEQ ID NO:1061): MIDPSDSFTSYSPSFQG;

CDR3 VH (SEQ ID NO:1062): LHYYNSEEFDV;

CDR1 VL (SEQ ID NO:1064): RASQSVSSSYLA;

CDR2 VL (SEQ ID NO:1065): GQSSRTR;

CDR3 VL (SEQ ID NO:1066): QQFGDTQLFT.

In one embodiment, the bispecific antibody is bimAb05-5386, wherein the arm to FIX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:52): DYAMH;

CDR2 VH (SEQ ID NO:53): GISWRGDIGGYVKSVKG;

CDR3 VH (SEQ ID NO:54): SYGSGSFYNAFDS;

CDR1 VL (SEQ ID NO:56): RASQSISSWLA;

CDR2 VL (SEQ ID NO:57): KASKLER;

CDR3 VL (SEQ ID NO:58): LEYSSYIRT;

and where the arm to FX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:1044): TSWIS;

CDR2 VH (SEQ ID NO:1045): MIDPSDSYTSYSPSFQG;

CDR3 VH (SEQ ID NO:1046): LHYYHSEEFDV;

CDR1 VL (SEQ ID NO:1048): RASQSVSSSYLA;

CDR2 VL (SEQ ID NO:1049): GQSSRTR;

CDR3 VL (SEQ ID NO:1050): QQFGDTQLFT.

In one embodiment, the bispecific antibody is bimAb05-5387, wherein the arm to FIX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:52): DYAMH;

CDR2 VH (SEQ ID NO:53): GISWRGDIGGYVKSVKG;

CDR3 VH (SEQ ID NO:54): SYGSGSFYNAFDS;

CDR1 VL (SEQ ID NO:56): RASQSISSWLA;

CDR2 VL (SEQ ID NO:57): KASKLER;

CDR3 VL (SEQ ID NO:58): LEYSSYIRT;

and where the arm to FX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:1068): TSWIV;

CDR2 VH (SEQ ID NO:1069): MIDPSDSYTSYSPSFQG;

CDR3 VH (SEQ ID NO:1070): LHYYNSEEFDV;

CDR1 VL (SEQ ID NO:1072): RASQSVSSSYLA;

CDR2 VL (SEQ ID NO:1073): GQSSRTR;

CDR3 VL (SEQ ID NO:1074): QQFGDTQLFT.

In one embodiment, the bispecific antibody is bimAb05-5388, wherein the arm to FIX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:52): DYAMH;

CDR2 VH (SEQ ID NO:53): GISWRGDIGGYVKSVKG;

CDR3 VH (SEQ ID NO:54): SYGSGSFYNAFDS;

CDR1 VL (SEQ ID NO:56): RASQSISSWLA;

CDR2 VL (SEQ ID NO:57): KASKLER;

CDR3 VL (SEQ ID NO:58): LEYSSYIRT;

and where the arm to FX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:1076): TSWIV;

CDR2 VH (SEQ ID NO:1077): MIDPSDSYTSYSPSFQG;

CDR3 VH (SEQ ID NO:1078): LHYYNSEEFDV;

CDR1 VL (SEQ ID NO:1080): RASQSVSSSYLA;

CDR2 VL (SEQ ID NO:1081): GQSSRTR;

CDR3 VL (SEQ ID NO:1082): QQFGDTQLFT.

In one embodiment, the bispecific antibody is bimAb05-5389, wherein the arm to FIX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:52): DYAMH;

CDR2 VH (SEQ ID NO:53): GISWRGDIGGYVKSVKG;

CDR3 VH (SEQ ID NO:54): SYGSGSFYNAFDS;

CDR1 VL (SEQ ID NO:56): RASQSISSWLA;

CDR2 VL (SEQ ID NO:57): KASKLER;

CDR3 VL (SEQ ID NO:58): LEYSSYIRT;

and where the arm to FX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:1100): TSWIS;

CDR2 VH (SEQ ID NO:1101): MIDPSDSYTSYSPSFQG;

CDR3 VH (SEQ ID NO:1102): LHYYHSEEFDV;

CDR1 VL (SEQ ID NO:1104): RASQSVSSSYLA;

CDR2 VL (SEQ ID NO:1105): GQSSRTR;

CDR3 VL (SEQ ID NO:1106): QQFGDNQLFT.

In one embodiment, the bispecific antibody is bimAb05-5390, wherein the arm to FIX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:52): DYAMH;

CDR2 VH (SEQ ID NO:53): GISWRGDIGGYVKSVKG;

CDR3 VH (SEQ ID NO:54): SYGSGSFYNAFDS;

CDR1 VL (SEQ ID NO:56): RASQSISSWLA;

CDR2 VL (SEQ ID NO:57): KASKLER;

CDR3 VL (SEQ ID NO:58): LEYSSYIRT;

and where the arm to FX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:756): TSWIV;

CDR2 VH (SEQ ID NO:757): MIDPSDSFTSYSPSFQG;

CDR3 VH (SEQ ID NO:758): LHYYNSEEFDV;

CDR1 VL (SEQ ID NO:760): RASQSVSSSYLA;

CDR2 VL (SEQ ID NO:761): GQSSRTR;

CDR3 VL (SEQ ID NO:762): QQFGDNQLFT.

In one embodiment, the bispecific antibody is bimAb05-5391, wherein the arm to FIX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:52): DYAMH;

CDR2 VH (SEQ ID NO:53): GISWRGDIGGYVKSVKG;

CDR3 VH (SEQ ID NO:54): SYGSGSFYNAFDS;

CDR1 VL (SEQ ID NO:56): RASQSISSWLA;

CDR2 VL (SEQ ID NO:57): KASKLER;

CDR3 VL (SEQ ID NO:58): LEYSSYIRT;

and where the arm to FX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:1108): TSWIS;

CDR2 VH (SEQ ID NO:1109): MIDPSDSYTSYSPSFQG;

CDR3 VH (SEQ ID NO:1110): LHYYHSEEFDV;

CDR1 VL (SEQ ID NO:1112): RASQSVSSSYLA;

CDR2 VL (SEQ ID NO:1113): GQSSRTR;

CDR3 VL (SEQ ID NO:1114): QQFGDNQLFT.

In one embodiment, the bispecific antibody is bimAb05-5392, wherein the arm to FIX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:52): DYAMH;

CDR2 VH (SEQ ID NO:53): GISWRGDIGGYVKSVKG;

CDR3 VH (SEQ ID NO:54): SYGSGSFYNAFDS;

CDR1 VL (SEQ ID NO:56): RASQSISSWLA;

CDR2 VL (SEQ ID NO:57): KASKLER;

CDR3 VL (SEQ ID NO:58): LEYSSYIRT;

and where the arm to FX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:1084): TSWIS;

CDR2 VH (SEQ ID NO:1085): MIDPSDSYTSYSPSFQG;

CDR3 VH (SEQ ID NO:1086): LHYYNSEEFDV;

CDR1 VL (SEQ ID NO:1088): RASQSVSSSYLA;

CDR2 VL (SEQ ID NO:1089): GQSSRTR;

CDR3 VL (SEQ ID NO:1090): QQFGDNQLFT.

In one embodiment, the bispecific antibody is bimAb05-5393, wherein the arm to FIX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:52): DYAMH;

CDR2 VH (SEQ ID NO:53): GISWRGDIGGYVKSVKG;

CDR3 VH (SEQ ID NO:54): SYGSGSFYNAFDS;

CDR1 VL (SEQ ID NO:56): RASQSISSWLA;

CDR2 VL (SEQ ID NO:57): KASKLER;

CDR3 VL (SEQ ID NO:58): LEYSSYIRT;

and where the arm to FX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:1116): TSWIS;

CDR2 VH (SEQ ID NO:1117): MIDPSDSFTSYSPSFQG;

CDR3 VH (SEQ ID NO:1118): LHYYNSEEFDV;

CDR1 VL (SEQ ID NO:1120): RASQSVSSSYLA;

CDR2 VL (SEQ ID NO:1121): GQSSRTR;

CDR3 VL (SEQ ID NO:1122): QQFGDNQLFT.

In one embodiment, the bispecific antibody is bimAb05-5394, wherein the arm to FIX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:52): DYAMH;

CDR2 VH (SEQ ID NO:53): GISWRGDIGGYVKSVKG;

CDR3 VH (SEQ ID NO:54): SYGSGSFYNAFDS;

CDR1 VL (SEQ ID NO:56): RASQSISSWLA;

CDR2 VL (SEQ ID NO:57): KASKLER;

CDR3 VL (SEQ ID NO:58): LEYSSYIRT;

and where the arm to FX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:1092): TSWIS;

CDR2 VH (SEQ ID NO:1093): MIDPSDSFTSYSPSFQG;

CDR3 VH (SEQ ID NO:1094): LHYYHSEEFDV;

CDR1 VL (SEQ ID NO:1096): RASQSVSSSYLA;

CDR2 VL (SEQ ID NO:1097): GQSSRTR;

CDR3 VL (SEQ ID NO:1098): QQFGDNQLFT.

In one embodiment, the bispecific antibody is bimAb05-5395, wherein the arm to FIX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:52): DYAMH;

CDR2 VH (SEQ ID NO:53): GISWRGDIGGYVKSVKG;

CDR3 VH (SEQ ID NO:54): SYGSGSFYNAFDS;

CDR1 VL (SEQ ID NO:56): RASQSISSWLA;

CDR2 VL (SEQ ID NO:57): KASKLER;

CDR3 VL (SEQ ID NO:58): LEYSSYIRT;

and where the arm to FX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:1124): TSWIV;

CDR2 VH (SEQ ID NO:1125): MIDPSDSYTSYSPSFQG;

CDR3 VH (SEQ ID NO:1126): LHYYNSEEFDV;

CDR1 VL (SEQ ID NO:1128): RASQSVSSSYLA;

CDR2 VL (SEQ ID NO:1129): GQSSRTR;

CDR3 VL (SEQ ID NO:1130): QQFGDNQLFT.

In one embodiment, the bispecific antibody is bimAb05-5396, wherein the arm to FIX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:52): DYAMH;

CDR2 VH (SEQ ID NO:53): GISWRGDIGGYVKSVKG;

CDR3 VH (SEQ ID NO:54): SYGSGSFYNAFDS;

CDR1 VL (SEQ ID NO:56): RASQSISSWLA;

CDR2 VL (SEQ ID NO:57): KASKLER;

CDR3 VL (SEQ ID NO:58): LEYSSYIRT;

and where the arm to FX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:1132): TSWIV;

CDR2 VH (SEQ ID NO:1133): MIDPSDSYTSYSPSFQG;

CDR3 VH (SEQ ID NO:1134): LHYYNSEEFDV;

CDR1 VL (SEQ ID NO:1136): RASQSVSSSYLA;

CDR2 VL (SEQ ID NO:1137): GQSSRTR;

CDR3 VL (SEQ ID NO:1138): QQFGDNQLFT.

In one embodiment, the bispecific antibody is bimAb05-5397, wherein the arm to FIX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:52): DYAMH;

CDR2 VH (SEQ ID NO:53): GISWRGDIGGYVKSVKG;

CDR3 VH (SEQ ID NO:54): SYGSGSFYNAFDS;

CDR1 VL (SEQ ID NO:56): RASQSISSWLA;

CDR2 VL (SEQ ID NO:57): KASKLER;

CDR3 VL (SEQ ID NO:58): LEYSSYIRT;

and where the arm to FX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:1156): TSWIS;

CDR2 VH (SEQ ID NO:1157): MIDPSDSYTSYSPSFQG;

CDR3 VH (SEQ ID NO:1158): LHYYHSEEFDV;

CDR1 VL (SEQ ID NO:1160): RASQSVSSSYLA;

CDR2 VL (SEQ ID NO:1161): GQSSRTR;

CDR3 VL (SEQ ID NO:1162): QQFGDDQLFT.

In one embodiment, the bispecific antibody is bimAb05-5399, wherein the arm to FIX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:52): DYAMH;

CDR2 VH (SEQ ID NO:53): GISWRGDIGGYVKSVKG;

CDR3 VH (SEQ ID NO:54): SYGSGSFYNAFDS;

CDR1 VL (SEQ ID NO:56): RASQSISSWLA;

CDR2 VL (SEQ ID NO:57): KASKLER;

CDR3 VL (SEQ ID NO:58): LEYSSYIRT;

and where the arm to FX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:1164): TSWIS;

CDR2 VH (SEQ ID NO:1165): MIDPSDSYTSYSPSFQG;

CDR3 VH (SEQ ID NO:1166): LHYYHSEEFDV;

CDR1 VL (SEQ ID NO:1168): RASQSVSSSYLA;

CDR2 VL (SEQ ID NO:1169): GQSSRTR;

CDR3 VL (SEQ ID NO:1170): QQFGDDQLFT.

In one embodiment, the bispecific antibody is bimAb05-5400, wherein the arm to FIX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:52): DYAMH;

CDR2 VH (SEQ ID NO:53): GISWRGDIGGYVKSVKG;

CDR3 VH (SEQ ID NO:54): SYGSGSFYNAFDS;

CDR1 VL (SEQ ID NO:56): RASQSISSWLA;

CDR2 VL (SEQ ID NO:57): KASKLER;

CDR3 VL (SEQ ID NO:58): LEYSSYIRT;

and where the arm to FX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:1140): TSWIS;

CDR2 VH (SEQ ID NO:1141): MIDPSDSYTSYSPSFQG;

CDR3 VH (SEQ ID NO:1142): LHYYNSEEFDV;

CDR1 VL (SEQ ID NO:1144): RASQSVSSSYLA;

CDR2 VL (SEQ ID NO:1145): GQSSRTR;

CDR3 VL (SEQ ID NO:1146): QQFGDDQLFT.

In one embodiment, the bispecific antibody is bimAb05-5401, wherein the arm to FIX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:52): DYAMH;

CDR2 VH (SEQ ID NO:53): GISWRGDIGGYVKSVKG;

CDR3 VH (SEQ ID NO:54): SYGSGSFYNAFDS;

CDR1 VL (SEQ ID NO:56): RASQSISSWLA;

CDR2 VL (SEQ ID NO:57): KASKLER;

CDR3 VL (SEQ ID NO:58): LEYSSYIRT;

and where the arm to FX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:1172): TSWIS;

CDR2 VH (SEQ ID NO:1173): MIDPSDSFTSYSPSFQG;

CDR3 VH (SEQ ID NO:1174): LHYYNSEEFDV;

CDR1 VL (SEQ ID NO:1176): RASQSVSSSYLA;

CDR2 VL (SEQ ID NO:1177): GQSSRTR;

CDR3 VL (SEQ ID NO:1178): QQFGDDQLFT.

In one embodiment, the bispecific antibody is bimAb05-5402, wherein the arm to FIX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:52): DYAMH;

CDR2 VH (SEQ ID NO:53): GISWRGDIGGYVKSVKG;

CDR3 VH (SEQ ID NO:54): SYGSGSFYNAFDS;

CDR1 VL (SEQ ID NO:56): RASQSISSWLA;

CDR2 VL (SEQ ID NO:57): KASKLER;

CDR3 VL (SEQ ID NO:58): LEYSSYIRT;

and where the arm to FX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:1148): TSWIS;

CDR2 VH (SEQ ID NO:1149): MIDPSDSFTSYSPSFQG;

CDR3 VH (SEQ ID NO:1150): LHYYHSEEFDV;

CDR1 VL (SEQ ID NO:1152): RASQSVSSSYLA;

CDR2 VL (SEQ ID NO:1153): GQSSRTR;

CDR3 VL (SEQ ID NO:1154): QQFGDDQLFT.

In one embodiment, the bispecific antibody is bimAb05-5403, wherein the arm to FIX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:52): DYAMH;

CDR2 VH (SEQ ID NO:53): GISWRGDIGGYVKSVKG;

CDR3 VH (SEQ ID NO:54): SYGSGSFYNAFDS;

CDR1 VL (SEQ ID NO:56): RASQSISSWLA;

CDR2 VL (SEQ ID NO:57): KASKLER;

CDR3 VL (SEQ ID NO:58): LEYSSYIRT;

and where the arm to FX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:1180): TSWIV;

CDR2 VH (SEQ ID NO:1181): MIDPSDSYTSYSPSFQG;

CDR3 VH (SEQ ID NO:1182): LHYYNSEEFDV;

CDR1 VL (SEQ ID NO:1184): RASQSVSSSYLA;

CDR2 VL (SEQ ID NO:1185): GQSSRTR;

CDR3 VL (SEQ ID NO:1186): QQFGDDQLFT.

In one embodiment, the bispecific antibody is bimAb05-5406, wherein the arm to FIX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:52): DYAMH;

CDR2 VH (SEQ ID NO:53): GISWRGDIGGYVKSVKG;

CDR3 VH (SEQ ID NO:54): SYGSGSFYNAFDS;

CDR1 VL (SEQ ID NO:56): RASQSISSWLA;

CDR2 VL (SEQ ID NO:57): KASKLER;

CDR3 VL (SEQ ID NO:58): LEYSSYIRT;

and where the arm to FX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:1188): TSWIV;

CDR2 VH (SEQ ID NO:1189): MIDPSDSYTSYSPSFQG;

CDR3 VH (SEQ ID NO:1190): LHYYNSEEFDV;

CDR1 VL (SEQ ID NO:1192): RASQSVSSSYLA;

CDR2 VL (SEQ ID NO:1193): GQSSRTR;

CDR3 VL (SEQ ID NO:1194): QQFGDDQLFT.

In one embodiment, the bispecific antibody is bimAb05-5413, wherein the arm to FIX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:52): DYAMH;

CDR2 VH (SEQ ID NO:53): GISWRGDIGGYVKSVKG;

CDR3 VH (SEQ ID NO:54): SYGSGSFYNAFDS;

CDR1 VL (SEQ ID NO:56): RASQSISSWLA;

CDR2 VL (SEQ ID NO:57): KASKLER;

CDR3 VL (SEQ ID NO:58): LEYSSYIRT;

and where the arm to FX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:548): TSWIV;

CDR2 VH (SEQ ID NO:549): MIDPSDSYTSYSPSFQG;

CDR3 VH (SEQ ID NO:550): LHYYNSEEFDV;

CDR1 VL (SEQ ID NO:552): RASQSVSSSYLA;

CDR2 VL (SEQ ID NO:553): GQSSRTR;

CDR3 VL (SEQ ID NO:554): QQFGDSQLFT.

In one embodiment, the bispecific antibody is bimAb05-4271, wherein the arm to FIX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:1203): DYAMH;

CDR2 VH (SEQ ID NO:1204): GISWKGDIGGYVDSVKG;

CDR3 VH (SEQ ID NO:1205): SYGSGSFYNAFDS;

CDR1 VL (SEQ ID NO:1207): RASQSISSWLA;

CDR2 VL (SEQ ID NO:1208): KASKLDR;

CDR3 VL (SEQ ID NO:1209): LEYSSYIRT;

and where the arm to FX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:468): TSWIV;

CDR2 VH (SEQ ID NO:469): MIDPSDSFTSYSPSFQG;

CDR3 VH (SEQ ID NO:470): LHYYNSEEFDV;

CDR1 VL (SEQ ID NO:472): RASQSVSSSYLA;

CDR2 VL (SEQ ID NO:473): GQSSRTR;

CDR3 VL (SEQ ID NO:474): QQFGDSQLFT.

In one embodiment, the bispecific antibody is bimAb05-4756, wherein the arm to FIX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:1211): DYAMH;

CDR2 VH (SEQ ID NO:1212): GISWRGDIGGYVKSVKG;

CDR3 VH (SEQ ID NO:1213): SYGSGSFYNAFDS;

CDR1 VL (SEQ ID NO:1215): RASQSISSWLA;

CDR2 VL (SEQ ID NO:1216): KASKLER;

CDR3 VL (SEQ ID NO:1217): LEYSSYIRT;

and where the arm to FX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:468): TSWIV;

CDR2 VH (SEQ ID NO:469): MIDPSDSFTSYSPSFQG;

CDR3 VH (SEQ ID NO:470): LHYYNSEEFDV;

CDR1 VL (SEQ ID NO:472): RASQSVSSSYLA;

CDR2 VL (SEQ ID NO:473): GQSSRTR;

CDR3 VL (SEQ ID NO:474): QQFGDSQLFT.

In one embodiment, the bispecific antibody is bimAb05-0396, wherein the arm to FIX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:1219): DYAMH;

CDR2 VH (SEQ ID NO:1220): GISWRGDIGGYAKSVKG;

CDR3 VH (SEQ ID NO:1221): SYGSGSFYNAFDS;

CDR1 VL (SEQ ID NO:1223): RASQSISSWLA;

CDR2 VL (SEQ ID NO:1224): KASKLDR;

CDR3 VL (SEQ ID NO:1225): LEYSSYIRT;

and where the arm to FX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:468): TSWIV;

CDR2 VH (SEQ ID NO:469): MIDPSDSFTSYSPSFQG;

CDR3 VH (SEQ ID NO:470): LHYYNSEEFDV;

CDR1 VL (SEQ ID NO:472): RASQSVSSSYLA;

CDR2 VL (SEQ ID NO:473): GQSSRTR;

CDR3 VL (SEQ ID NO:474): QQFGDSQLFT.

In one embodiment, the bispecific antibody is bimAb05-0417, wherein the arm to FIX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:1227): DYAMH;

CDR2 VH (SEQ ID NO:1228): GISWRGDIGGYVKSVKG;

CDR3 VH (SEQ ID NO:1229): SYGSGSFYNAFDS;

CDR1 VL (SEQ ID NO:1231): RASQSISSWLA;

CDR2 VL (SEQ ID NO:1232): KASKLDR;

CDR3 VL (SEQ ID NO:1233): LEYSSYIRT;

and where the arm to FX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:468): TSWIV;

CDR2 VH (SEQ ID NO:469): MIDPSDSFTSYSPSFQG;

CDR3 VH (SEQ ID NO:470): LHYYNSEEFDV;

CDR1 VL (SEQ ID NO:472): RASQSVSSSYLA;

CDR2 VL (SEQ ID NO:473): GQSSRTR;

CDR3 VL (SEQ ID NO:474): QQFGDSQLFT.

In one embodiment, the bispecific antibody is bimAb05-0438, wherein the arm to FIX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:1235): DYAMH;

CDR2 VH (SEQ ID NO:1236): GISWRGDIGGYVKSVKG;

CDR3 VH (SEQ ID NO:1237): SYGSGSFYNAFDS;

CDR1 VL (SEQ ID NO:1239): RASQSISSWLA;

CDR2 VL (SEQ ID NO:1240): KASKLDR;

CDR3 VL (SEQ ID NO:1241): LEYSSYIRT;

and where the arm to FX(a) contains the following CDR sequences:

CDR1 VH (SEQ ID NO:468): TSWIV;

CDR2 VH (SEQ ID NO:469): MIDPSDSFTSYSPSFQG;

CDR3 VH (SEQ ID NO:470): LHYYNSEEFDV;

CDR1 VL (SEQ ID NO:472): RASQSVSSSYLA;

CDR2 VL (SEQ ID NO:473): GQSSRTR;

CDR3 VL (SEQ ID NO:474): QQFGDSQLFT.

In one embodiment, the bispecific antibody comprises the VH and VL arm domains of FIX(a) corresponding to SEQ ID NO:67 and SEQ ID NO:71, respectively, and

VH and VL arm domains to FX(a), corresponding to SEQ ID NO:467 and SEQ ID NO:471, respectively.

In one embodiment, the bispecific antibody comprises the VH and VL arm domains of FIX(a) corresponding to SEQ ID NO:43 and SEQ ID NO:47, respectively, and

VH and VL arm domains to FX(a), corresponding to SEQ ID NO:467 and SEQ ID NO:471, respectively.

In one embodiment, the bispecific antibody comprises the VH and VL arm domains of FIX(a) corresponding to SEQ ID NO:3 and SEQ ID NO:7, respectively, and

VH and VL arm domains to FX(a), corresponding to SEQ ID NO:459 and SEQ ID NO:463, respectively.

In one embodiment, the bispecific antibody comprises the VH and VL arm domains of FIX(a) corresponding to SEQ ID NO:67 and SEQ ID NO:71, respectively, and

VH and VL arm domains to FX(a), corresponding to SEQ ID NO:483 and SEQ ID NO:487, respectively.

In one embodiment, the bispecific antibody comprises the VH and VL arm domains of FIX(a) corresponding to SEQ ID NO:35 and SEQ ID NO:39, respectively, and

VH and VL arm domains to FX(a), corresponding to SEQ ID NO:483 and SEQ ID NO:487, respectively.

In one embodiment, the bispecific antibody comprises the VH and VL arm domains of FIX(a) corresponding to SEQ ID NO:51 and SEQ ID NO:55, respectively, and

VH and VL arm domains to FX(a), corresponding to SEQ ID NO:483 and SEQ ID NO:487, respectively.

In one embodiment, the bispecific antibody comprises the VH and VL arm domains of FIX(a) corresponding to SEQ ID NO:43 and SEQ ID NO:47, respectively, and

VH and VL arm domains to FX(a), corresponding to SEQ ID NO:483 and SEQ ID NO:487, respectively.

In one embodiment, the bispecific antibody comprises the VH and VL arm domains of FIX(a) corresponding to SEQ ID NO:3 and SEQ ID NO:7, respectively, and

VH and VL arm domains to FX(a), corresponding to SEQ ID NO:467 and SEQ ID NO:471, respectively.

In one embodiment, the bispecific antibody comprises the VH and VL arm domains of FIX(a) corresponding to SEQ ID NO:3 and SEQ ID NO:7, respectively, and

VH and VL arm domains to FX(a), corresponding to SEQ ID NO:475 and SEQ ID NO:479, respectively.

In one embodiment, the bispecific antibody comprises the VH and VL arm domains of FIX(a) corresponding to SEQ ID NO:11 and SEQ ID NO:15, respectively, and

VH and VL arm domains to FX(a), corresponding to SEQ ID NO:459 and SEQ ID NO:463, respectively.

In one embodiment, the bispecific antibody comprises the VH and VL arm domains of FIX(a) corresponding to SEQ ID NO:35 and SEQ ID NO:39, respectively, and

VH and VL arm domains to FX(a), corresponding to SEQ ID NO:459 and SEQ ID NO:463, respectively.

In one embodiment, the bispecific antibody comprises the VH and VL arm domains of FIX(a) corresponding to SEQ ID NO:43 and SEQ ID NO:47, respectively, and

VH and VL arm domains to FX(a), corresponding to SEQ ID NO:459 and SEQ ID NO:463, respectively.

In one embodiment, the bispecific antibody comprises the VH and VL arm domains of FIX(a) corresponding to SEQ ID NO:51 and SEQ ID NO:55, respectively, and

VH and VL arm domains to FX(a), corresponding to SEQ ID NO:459 and SEQ ID NO:463, respectively.

In one embodiment, the bispecific antibody comprises the VH and VL arm domains of FIX(a) corresponding to SEQ ID NO:67 and SEQ ID NO:71, respectively, and

VH and VL arm domains to FX(a), corresponding to SEQ ID NO:459 and SEQ ID NO:463, respectively.

In one embodiment, the bispecific antibody comprises the VH and VL arm domains of FIX(a) corresponding to SEQ ID NO:35 and SEQ ID NO:39, respectively, and

VH and VL arm domains to FX(a), corresponding to SEQ ID NO:467 and SEQ ID NO:471, respectively.

In one embodiment, the bispecific antibody comprises the VH and VL arm domains of FIX(a) corresponding to SEQ ID NO:51 and SEQ ID NO:55, respectively, and

VH and VL arm domains to FX(a), corresponding to SEQ ID NO:467 and SEQ ID NO:471, respectively.

In one embodiment, the bispecific antibody comprises the VH and VL arm domains of FIX(a) corresponding to SEQ ID NO:59 and SEQ ID NO:63, respectively, and

VH and VL arm domains to FX(a), corresponding to SEQ ID NO:467 and SEQ ID NO:471, respectively.

In one embodiment, the bispecific antibody comprises the VH and VL arm domains of FIX(a) corresponding to SEQ ID NO:19 and SEQ ID NO:23, respectively, and

VH and VL arm domains to FX(a), corresponding to SEQ ID NO:467 and SEQ ID NO:471, respectively.

In one embodiment, the bispecific antibody comprises the VH and VL arm domains of FIX(a) corresponding to SEQ ID NO:27 and SEQ ID NO:31, respectively, and

VH and VL arm domains to FX(a), corresponding to SEQ ID NO:467 and SEQ ID NO:471, respectively.

In one embodiment, the bispecific antibody comprises the VH and VL arm domains of FIX(a) corresponding to SEQ ID NO:75 and SEQ ID NO:79, respectively, and

VH and VL arm domains to FX(a), corresponding to SEQ ID NO:467 and SEQ ID NO:471, respectively.

In one embodiment, the bispecific antibody comprises the VH and VL arm domains of FIX(a) corresponding to SEQ ID NO:83 and SEQ ID NO:87, respectively, and

VH and VL arm domains to FX(a), corresponding to SEQ ID NO:467 and SEQ ID NO:471, respectively.

In one embodiment, the bispecific antibody comprises the VH and VL arm domains of FIX(a) corresponding to SEQ ID NO:91 and SEQ ID NO:95, respectively, and

VH and VL arm domains to FX(a), corresponding to SEQ ID NO:467 and SEQ ID NO:471, respectively.

In one embodiment, the bispecific antibody comprises the VH and VL arm domains of FIX(a) corresponding to SEQ ID NO:99 and SEQ ID NO:103, respectively, and

VH and VL arm domains to FX(a), corresponding to SEQ ID NO:467 and SEQ ID NO:471, respectively.

In one embodiment, the bispecific antibody comprises the VH and VL arm domains of FIX(a) corresponding to SEQ ID NO:107 and SEQ ID NO:111, respectively, and

VH and VL arm domains to FX(a), corresponding to SEQ ID NO:467 and SEQ ID NO:471, respectively.

In one embodiment, the bispecific antibody comprises the VH and VL arm domains of FIX(a) corresponding to SEQ ID NO:115 and SEQ ID NO:119, respectively, and

VH and VL arm domains to FX(a), corresponding to SEQ ID NO:467 and SEQ ID NO:471, respectively.

In one embodiment, the bispecific antibody comprises the VH and VL arm domains of FIX(a) corresponding to SEQ ID NO:211 and SEQ ID NO:215, respectively, and

VH and VL arm domains to FX(a), corresponding to SEQ ID NO:467 and SEQ ID NO:471, respectively.

In one embodiment, the bispecific antibody comprises the VH and VL arm domains of FIX(a) corresponding to SEQ ID NO:219 and SEQ ID NO:223, respectively, and

VH and VL arm domains to FX(a), corresponding to SEQ ID NO:467 and SEQ ID NO:471, respectively.

In one embodiment, the bispecific antibody comprises the VH and VL arm domains of FIX(a) corresponding to SEQ ID NO:227 and SEQ ID NO:231, respectively, and

VH and VL arm domains to FX(a), corresponding to SEQ ID NO:467 and SEQ ID NO:471, respectively.

In one embodiment, the bispecific antibody comprises the VH and VL arm domains of FIX(a) corresponding to SEQ ID NO:235 and SEQ ID NO:239, respectively, and

VH and VL arm domains to FX(a), corresponding to SEQ ID NO:467 and SEQ ID NO:471, respectively.

In one embodiment, the bispecific antibody comprises the VH and VL arm domains of FIX(a) corresponding to SEQ ID NO:251 and SEQ ID NO:255, respectively, and

VH and VL arm domains to FX(a), corresponding to SEQ ID NO:467 and SEQ ID NO:471, respectively.

In one embodiment, the bispecific antibody comprises the VH and VL arm domains of FIX(a) corresponding to SEQ ID NO:243 and SEQ ID NO:247, respectively, and

VH and VL arm domains to FX(a), corresponding to SEQ ID NO:467 and SEQ ID NO:471, respectively.

In one embodiment, the bispecific antibody comprises the VH and VL arm domains of FIX(a) corresponding to SEQ ID NO:259 and SEQ ID NO:263, respectively, and

VH and VL arm domains to FX(a), corresponding to SEQ ID NO:467 and SEQ ID NO:471, respectively.

In one embodiment, the bispecific antibody comprises the VH and VL arm domains of FIX(a) corresponding to SEQ ID NO:267 and SEQ ID NO:271, respectively, and

VH and VL arm domains to FX(a), corresponding to SEQ ID NO:467 and SEQ ID NO:471, respectively.

In one embodiment, the bispecific antibody comprises the VH and VL arm domains of FIX(a) corresponding to SEQ ID NO:123 and SEQ ID NO:127, respectively, and

VH and VL arm domains to FX(a), corresponding to SEQ ID NO:467 and SEQ ID NO:471, respectively.

In one embodiment, the bispecific antibody comprises the VH and VL arm domains of FIX(a) corresponding to SEQ ID NO:275 and SEQ ID NO:279, respectively, and

VH and VL arm domains to FX(a), corresponding to SEQ ID NO:467 and SEQ ID NO:471, respectively.

In one embodiment, the bispecific antibody comprises the VH and VL arm domains of FIX(a) corresponding to SEQ ID NO:283 and SEQ ID NO:287, respectively, and

VH and VL arm domains to FX(a), corresponding to SEQ ID NO:467 and SEQ ID NO:471, respectively.

In one embodiment, the bispecific antibody comprises the VH and VL arm domains of FIX(a) corresponding to SEQ ID NO:299 and SEQ ID NO:303, respectively, and

VH and VL arm domains to FX(a), corresponding to SEQ ID NO:467 and SEQ ID NO:471, respectively.

In one embodiment, the bispecific antibody comprises the VH and VL arm domains of FIX(a) corresponding to SEQ ID NO:291 and SEQ ID NO:295, respectively, and

VH and VL arm domains to FX(a), corresponding to SEQ ID NO:467 and SEQ ID NO:471, respectively.

In one embodiment, the bispecific antibody comprises the VH and VL arm domains of FIX(a) corresponding to SEQ ID NO:187 and SEQ ID NO:191, respectively, and

VH and VL arm domains to FX(a), corresponding to SEQ ID NO:467 and SEQ ID NO:471, respectively.

In one embodiment, the bispecific antibody comprises the VH and VL arm domains of FIX(a) corresponding to SEQ ID NO:139 and SEQ ID NO:143, respectively, and

VH and VL arm domains to FX(a), corresponding to SEQ ID NO:467 and SEQ ID NO:471, respectively.

In one embodiment, the bispecific antibody comprises the VH and VL arm domains of FIX(a) corresponding to SEQ ID NO:203 and SEQ ID NO:207, respectively, and

VH and VL arm domains to FX(a), corresponding to SEQ ID NO:467 and SEQ ID NO:471, respectively.

In one embodiment, the bispecific antibody comprises the VH and VL arm domains of FIX(a) corresponding to SEQ ID NO:179 and SEQ ID NO:183, respectively, and

VH and VL arm domains to FX(a), corresponding to SEQ ID NO:467 and SEQ ID NO:471, respectively.

In one embodiment, the bispecific antibody comprises the VH and VL arm domains of FIX(a) corresponding to SEQ ID NO:195 and SEQ ID NO:199, respectively, and

VH and VL arm domains to FX(a), corresponding to SEQ ID NO:467 and SEQ ID NO:471, respectively.

In one embodiment, the bispecific antibody comprises the VH and VL arm domains of FIX(a) corresponding to SEQ ID NO:171 and SEQ ID NO:175, respectively, and

VH and VL arm domains to FX(a), corresponding to SEQ ID NO:467 and SEQ ID NO:471, respectively.

In one embodiment, the bispecific antibody comprises the VH and VL arm domains of FIX(a) corresponding to SEQ ID NO:163 and SEQ ID NO:167, respectively, and

VH and VL arm domains to FX(a), corresponding to SEQ ID NO:467 and SEQ ID NO:471, respectively.

In one embodiment, the bispecific antibody comprises the VH and VL arm domains of FIX(a) corresponding to SEQ ID NO:147 and SEQ ID NO:151, respectively, and

VH and VL arm domains to FX(a), corresponding to SEQ ID NO:467 and SEQ ID NO:471, respectively.

In one embodiment, the bispecific antibody comprises the VH and VL arm domains of FIX(a) corresponding to SEQ ID NO:155 and SEQ ID NO:159, respectively, and

VH and VL arm domains to FX(a), corresponding to SEQ ID NO:467 and SEQ ID NO:471, respectively.

In one embodiment, the bispecific antibody comprises the VH and VL arm domains of FIX(a) corresponding to SEQ ID NO:51 and SEQ ID NO:55, respectively, and

VH and VL arm domains to FX(a), corresponding to SEQ ID NO:499 and SEQ ID NO:503, respectively.

In one embodiment, the bispecific antibody comprises the VH and VL arm domains of FIX(a) corresponding to SEQ ID NO:51 and SEQ ID NO:55, respectively, and

VH and VL arm domains to FX(a), corresponding to SEQ ID NO:507 and SEQ ID NO:511, respectively.

In one embodiment, the bispecific antibody comprises the VH and VL arm domains of FIX(a) corresponding to SEQ ID NO:51 and SEQ ID NO:55, respectively, and

VH and VL arm domains to FX(a), corresponding to SEQ ID NO:515 and SEQ ID NO:519, respectively.

In one embodiment, the bispecific antibody comprises the VH and VL arm domains of FIX(a) corresponding to SEQ ID NO:51 and SEQ ID NO:55, respectively, and

VH and VL arm domains to FX(a), corresponding to SEQ ID NO:523 and SEQ ID NO:527, respectively.

In one embodiment, the bispecific antibody comprises the VH and VL arm domains of FIX(a) corresponding to SEQ ID NO:51 and SEQ ID NO:55, respectively, and

VH and VL arm domains to FX(a), corresponding to SEQ ID NO:531 and SEQ ID NO:535, respectively.

In one embodiment, the bispecific antibody comprises the VH and VL arm domains of FIX(a) corresponding to SEQ ID NO:51 and SEQ ID NO:55, respectively, and

VH and VL arm domains to FX(a), corresponding to SEQ ID NO:539 and SEQ ID NO:543, respectively.

In one embodiment, the bispecific antibody comprises the VH and VL arm domains of FIX(a) corresponding to SEQ ID NO:51 and SEQ ID NO:55, respectively, and

VH and VL arm domains to FX(a), corresponding to SEQ ID NO:555 and SEQ ID NO:559, respectively.

In one embodiment, the bispecific antibody comprises the VH and VL arm domains of FIX(a) corresponding to SEQ ID NO:51 and SEQ ID NO:55, respectively, and

VH and VL arm domains to FX(a), corresponding to SEQ ID NO:563 and SEQ ID NO:567, respectively.

In one embodiment, the bispecific antibody comprises the VH and VL arm domains of FIX(a) corresponding to SEQ ID NO:51 and SEQ ID NO:55, respectively, and

VH and VL arm domains to FX(a), corresponding to SEQ ID NO:571 and SEQ ID NO:575, respectively.

In one embodiment, the bispecific antibody comprises the VH and VL arm domains of FIX(a) corresponding to SEQ ID NO:51 and SEQ ID NO:55, respectively, and

VH and VL arm domains to FX(a), corresponding to SEQ ID NO:579 and SEQ ID NO:583, respectively.

In one embodiment, the bispecific antibody comprises the VH and VL arm domains of FIX(a) corresponding to SEQ ID NO:51 and SEQ ID NO:55, respectively, and

VH and VL arm domains to FX(a), corresponding to SEQ ID NO:491 and SEQ ID NO:495, respectively.

In one embodiment, the bispecific antibody comprises the VH and VL arm domains of FIX(a) corresponding to SEQ ID NO:51 and SEQ ID NO:55, respectively, and

VH and VL arm domains to FX(a), corresponding to SEQ ID NO:587 and SEQ ID NO:591, respectively.

In one embodiment, the bispecific antibody comprises the VH and VL arm domains of FIX(a) corresponding to SEQ ID NO:51 and SEQ ID NO:55, respectively, and

VH and VL arm domains to FX(a), corresponding to SEQ ID NO:595 and SEQ ID NO:599, respectively.

In one embodiment, the bispecific antibody comprises the VH and VL arm domains of FIX(a) corresponding to SEQ ID NO:51 and SEQ ID NO:55, respectively, and

VH and VL arm domains to FX(a), corresponding to SEQ ID NO:603 and SEQ ID NO:607, respectively.

In one embodiment, the bispecific antibody comprises the VH and VL arm domains of FIX(a) corresponding to SEQ ID NO:51 and SEQ ID NO:55, respectively, and

VH and VL arm domains to FX(a), corresponding to SEQ ID NO:611 and SEQ ID NO:615, respectively.

In one embodiment, the bispecific antibody comprises the VH and VL arm domains of FIX(a) corresponding to SEQ ID NO:51 and SEQ ID NO:55, respectively, and

VH and VL arm domains to FX(a), corresponding to SEQ ID NO:619 and SEQ ID NO:623, respectively.

In one embodiment, the bispecific antibody comprises the VH and VL arm domains of FIX(a) corresponding to SEQ ID NO:51 and SEQ ID NO:55, respectively, and

VH and VL arm domains to FX(a), corresponding to SEQ ID NO:627 and SEQ ID NO:631, respectively.

In one embodiment, the bispecific antibody comprises the VH and VL arm domains of FIX(a) corresponding to SEQ ID NO:51 and SEQ ID NO:55, respectively, and

VH and VL arm domains to FX(a), corresponding to SEQ ID NO:635 and SEQ ID NO:639, respectively.

In one embodiment, the bispecific antibody comprises the VH and VL arm domains of FIX(a) corresponding to SEQ ID NO:51 and SEQ ID NO:55, respectively, and

VH and VL arm domains to FX(a), corresponding to SEQ ID NO:643 and SEQ ID NO:647, respectively.

In one embodiment, the bispecific antibody comprises the VH and VL arm domains of FIX(a) corresponding to SEQ ID NO:51 and SEQ ID NO:55, respectively, and

VH and VL arm domains to FX(a), corresponding to SEQ ID NO:651 and SEQ ID NO:655, respectively.

In one embodiment, the bispecific antibody comprises the VH and VL arm domains of FIX(a) corresponding to SEQ ID NO:51 and SEQ ID NO:55, respectively, and

VH and VL arm domains to FX(a), corresponding to SEQ ID NO:659 and SEQ ID NO:663, respectively.

In one embodiment, the bispecific antibody comprises the VH and VL arm domains of FIX(a) corresponding to SEQ ID NO:51 and SEQ ID NO:55, respectively, and

VH and VL arm domains to FX(a), corresponding to SEQ ID NO:667 and SEQ ID NO:671, respectively.

In one embodiment, the bispecific antibody comprises the VH and VL arm domains of FIX(a) corresponding to SEQ ID NO:51 and SEQ ID NO:55, respectively, and

VH and VL arm domains to FX(a), corresponding to SEQ ID NO:675 and SEQ ID NO:679, respectively.

In one embodiment, the bispecific antibody comprises the VH and VL arm domains of FIX(a) corresponding to SEQ ID NO:51 and SEQ ID NO:55, respectively, and

VH and VL arm domains to FX(a), corresponding to SEQ ID NO:683 and SEQ ID NO:687, respectively.

In one embodiment, the bispecific antibody comprises the VH and VL arm domains of FIX(a) corresponding to SEQ ID NO:51 and SEQ ID NO:55, respectively, and

VH and VL arm domains to FX(a), corresponding to SEQ ID NO:691 and SEQ ID NO:695, respectively.

In one embodiment, the bispecific antibody comprises the VH and VL arm domains of FIX(a) corresponding to SEQ ID NO:51 and SEQ ID NO:55, respectively, and

VH and VL arm domains to FX(a), corresponding to SEQ ID NO:699 and SEQ ID NO:703, respectively.

In one embodiment, the bispecific antibody comprises the VH and VL arm domains of FIX(a) corresponding to SEQ ID NO:307 and SEQ ID NO:311, respectively, and

VH and VL arm domains to FX(a), corresponding to SEQ ID NO:467 and SEQ ID NO:471, respectively.

In one embodiment, the bispecific antibody comprises the VH and VL arm domains of FIX(a) corresponding to SEQ ID NO:315 and SEQ ID NO:319, respectively, and

VH and VL arm domains to FX(a), corresponding to SEQ ID NO:467 and SEQ ID NO:471, respectively.

In one embodiment, the bispecific antibody comprises the VH and VL arm domains of FIX(a) corresponding to SEQ ID NO:339 and SEQ ID NO:343, respectively, and

VH and VL arm domains to FX(a), corresponding to SEQ ID NO:467 and SEQ ID NO:471, respectively.

In one embodiment, the bispecific antibody comprises the VH and VL arm domains of FIX(a) corresponding to SEQ ID NO:323 and SEQ ID NO:327, respectively, and

VH and VL arm domains to FX(a), corresponding to SEQ ID NO:467 and SEQ ID NO:471, respectively.

In one embodiment, the bispecific antibody comprises the VH and VL arm domains of FIX(a) corresponding to SEQ ID NO:331 and SEQ ID NO:335, respectively, and

VH and VL arm domains to FX(a), corresponding to SEQ ID NO:467 and SEQ ID NO:471, respectively.

In one embodiment, the bispecific antibody comprises the VH and VL arm domains of FIX(a) corresponding to SEQ ID NO:355 and SEQ ID NO:359, respectively, and

VH and VL arm domains to FX(a), corresponding to SEQ ID NO:467 and SEQ ID NO:471, respectively.

In one embodiment, the bispecific antibody comprises the VH and VL arm domains of FIX(a) corresponding to SEQ ID NO:347 and SEQ ID NO:351, respectively, and

VH and VL arm domains to FX(a), corresponding to SEQ ID NO:467 and SEQ ID NO:471, respectively.

In one embodiment, the bispecific antibody comprises the VH and VL arm domains of FIX(a) corresponding to SEQ ID NO:363 and SEQ ID NO:367, respectively, and

VH and VL arm domains to FX(a), corresponding to SEQ ID NO:467 and SEQ ID NO:471, respectively.

In one embodiment, the bispecific antibody comprises the VH and VL arm domains of FIX(a) corresponding to SEQ ID NO:371 and SEQ ID NO:375, respectively, and

VH and VL arm domains to FX(a), corresponding to SEQ ID NO:467 and SEQ ID NO:471, respectively.

In one embodiment, the bispecific antibody comprises the VH and VL arm domains of FIX(a) corresponding to SEQ ID NO:379 and SEQ ID NO:383, respectively, and

VH and VL arm domains to FX(a), corresponding to SEQ ID NO:467 and SEQ ID NO:471, respectively.

In one embodiment, the bispecific antibody comprises the VH and VL arm domains of FIX(a) corresponding to SEQ ID NO:387 and SEQ ID NO:391, respectively, and

VH and VL arm domains to FX(a), corresponding to SEQ ID NO:467 and SEQ ID NO:471, respectively.

In one embodiment, the bispecific antibody comprises the VH and VL arm domains of FIX(a) corresponding to SEQ ID NO:403 and SEQ ID NO:407, respectively, and

VH and VL arm domains to FX(a), corresponding to SEQ ID NO:467 and SEQ ID NO:471, respectively.

In one embodiment, the bispecific antibody comprises the VH and VL arm domains of FIX(a) corresponding to SEQ ID NO:395 and SEQ ID NO:399, respectively, and

VH and VL arm domains to FX(a), corresponding to SEQ ID NO:467 and SEQ ID NO:471, respectively.

In one embodiment, the bispecific antibody comprises the VH and VL arm domains of FIX(a) corresponding to SEQ ID NO:419 and SEQ ID NO:423, respectively, and

VH and VL arm domains to FX(a), corresponding to SEQ ID NO:467 and SEQ ID NO:471, respectively.

In one embodiment, the bispecific antibody comprises the VH and VL arm domains of FIX(a) corresponding to SEQ ID NO:411 and SEQ ID NO:415, respectively, and

VH and VL arm domains to FX(a), corresponding to SEQ ID NO:467 and SEQ ID NO:471, respectively.

In one embodiment, the bispecific antibody comprises the VH and VL arm domains of FIX(a) corresponding to SEQ ID NO:427 and SEQ ID NO:431, respectively, and

VH and VL arm domains to FX(a), corresponding to SEQ ID NO:467 and SEQ ID NO:471, respectively.

In one embodiment, the bispecific antibody comprises the VH and VL arm domains of FIX(a) corresponding to SEQ ID NO:131 and SEQ ID NO:135, respectively, and

VH and VL arm domains to FX(a), corresponding to SEQ ID NO:467 and SEQ ID NO:471, respectively.

In one embodiment, the bispecific antibody comprises the VH and VL arm domains of FIX(a) corresponding to SEQ ID NO:435 and SEQ ID NO:439, respectively, and

VH and VL arm domains to FX(a), corresponding to SEQ ID NO:467 and SEQ ID NO:471, respectively.

In one embodiment, the bispecific antibody comprises the VH and VL arm domains of FIX(a) corresponding to SEQ ID NO:443 and SEQ ID NO:447, respectively, and

VH and VL arm domains to FX(a), corresponding to SEQ ID NO:467 and SEQ ID NO:471, respectively.

In one embodiment, the bispecific antibody comprises the VH and VL arm domains of FIX(a) corresponding to SEQ ID NO:451 and SEQ ID NO:455, respectively, and

VH and VL arm domains to FX(a), corresponding to SEQ ID NO:467 and SEQ ID NO:471, respectively.

In one embodiment, the bispecific antibody comprises the VH and VL arm domains of FIX(a) corresponding to SEQ ID NO:51 and SEQ ID NO:55, respectively, and

VH and VL arm domains to FX(a), corresponding to SEQ ID NO:771 and SEQ ID NO:775, respectively.

In one embodiment, the bispecific antibody comprises the VH and VL arm domains of FIX(a) corresponding to SEQ ID NO:51 and SEQ ID NO:55, respectively, and

VH and VL arm domains to FX(a), corresponding to SEQ ID NO:707 and SEQ ID NO:711, respectively.

In one embodiment, the bispecific antibody comprises the VH and VL arm domains of FIX(a) corresponding to SEQ ID NO:51 and SEQ ID NO:55, respectively, and

VH and VL arm domains to FX(a), corresponding to SEQ ID NO:779 and SEQ ID NO:783, respectively.

In one embodiment, the bispecific antibody comprises the VH and VL arm domains of FIX(a) corresponding to SEQ ID NO:51 and SEQ ID NO:55, respectively, and

VH and VL arm domains to FX(a), corresponding to SEQ ID NO:763 and SEQ ID NO:767, respectively.

In one embodiment, the bispecific antibody comprises the VH and VL arm domains of FIX(a) corresponding to SEQ ID NO:51 and SEQ ID NO:55, respectively, and

VH and VL arm domains to FX(a), corresponding to SEQ ID NO:787 and SEQ ID NO:791, respectively.

In one embodiment, the bispecific antibody comprises the VH and VL arm domains of FIX(a) corresponding to SEQ ID NO:51 and SEQ ID NO:55, respectively, and

VH and VL arm domains to FX(a), corresponding to SEQ ID NO:795 and SEQ ID NO:799, respectively.

In one embodiment, the bispecific antibody comprises the VH and VL arm domains of FIX(a) corresponding to SEQ ID NO:51 and SEQ ID NO:55, respectively, and

VH and VL arm domains to FX(a), corresponding to SEQ ID NO:819 and SEQ ID NO:823, respectively.

In one embodiment, the bispecific antibody comprises the VH and VL arm domains of FIX(a) corresponding to SEQ ID NO:51 and SEQ ID NO:55, respectively, and

VH and VL arm domains to FX(a), corresponding to SEQ ID NO:803 and SEQ ID NO:807, respectively.

In one embodiment, the bispecific antibody comprises the VH and VL arm domains of FIX(a) corresponding to SEQ ID NO:51 and SEQ ID NO:55, respectively, and

VH and VL arm domains to FX(a), corresponding to SEQ ID NO:827 and SEQ ID NO:831, respectively.

In one embodiment, the bispecific antibody comprises the VH and VL arm domains of FIX(a) corresponding to SEQ ID NO:51 and SEQ ID NO:55, respectively, and

VH and VL arm domains to FX(a), corresponding to SEQ ID NO:811 and SEQ ID NO:815, respectively.

In one embodiment, the bispecific antibody comprises the VH and VL arm domains of FIX(a) corresponding to SEQ ID NO:51 and SEQ ID NO:55, respectively, and

VH and VL arm domains to FX(a), corresponding to SEQ ID NO:835 and SEQ ID NO:839, respectively.

In one embodiment, the bispecific antibody comprises the VH and VL arm domains of FIX(a) corresponding to SEQ ID NO:51 and SEQ ID NO:55, respectively, and

VH and VL arm domains to FX(a), corresponding to SEQ ID NO:715 and SEQ ID NO:719, respectively.

In one embodiment, the bispecific antibody comprises the VH and VL arm domains of FIX(a) corresponding to SEQ ID NO:51 and SEQ ID NO:55, respectively, and

VH and VL arm domains to FX(a), corresponding to SEQ ID NO:843 and SEQ ID NO:847, respectively.

In one embodiment, the bispecific antibody comprises the VH and VL arm domains of FIX(a) corresponding to SEQ ID NO:51 and SEQ ID NO:55, respectively, and

VH and VL arm domains to FX(a), corresponding to SEQ ID NO:851 and SEQ ID NO:855, respectively.

In one embodiment, the bispecific antibody comprises the VH and VL arm domains of FIX(a) corresponding to SEQ ID NO:51 and SEQ ID NO:55, respectively, and

VH and VL arm domains to FX(a), corresponding to SEQ ID NO:875 and SEQ ID NO:879, respectively.

In one embodiment, the bispecific antibody comprises the VH and VL arm domains of FIX(a) corresponding to SEQ ID NO:51 and SEQ ID NO:55, respectively, and

VH and VL arm domains to FX(a), corresponding to SEQ ID NO:859 and SEQ ID NO:863, respectively. In one embodiment, the bispecific antibody comprises the VH and VL arm domains of FIX(a) corresponding to SEQ ID NO:51 and SEQ ID NO:55, respectively, and

VH and VL arm domains to FX(a), corresponding to SEQ ID NO:883 and SEQ ID NO:887, respectively. In one embodiment, the bispecific antibody comprises the VH and VL arm domains of FIX(a) corresponding to SEQ ID NO:51 and SEQ ID NO:55, respectively, and

VH and VL arm domains to FX(a), corresponding to SEQ ID NO:867 and SEQ ID NO:871, respectively. In one embodiment, the bispecific antibody comprises the VH and VL arm domains of FIX(a) corresponding to SEQ ID NO:51 and SEQ ID NO:55, respectively, and

VH and VL arm domains to FX(a), corresponding to SEQ ID NO:891 and SEQ ID NO:895, respectively. In one embodiment, the bispecific antibody comprises the VH and VL arm domains of FIX(a) corresponding to SEQ ID NO:51 and SEQ ID NO:55, respectively, and

VH and VL arm domains to FX(a), corresponding to SEQ ID NO:723 and SEQ ID NO:727, respectively. In one embodiment, the bispecific antibody comprises the VH and VL arm domains of FIX(a) corresponding to SEQ ID NO:51 and SEQ ID NO:55, respectively, and

VH and VL arm domains to FX(a), corresponding to SEQ ID NO:899 and SEQ ID NO:903, respectively. In one embodiment, the bispecific antibody comprises the VH and VL arm domains of FIX(a) corresponding to SEQ ID NO:51 and SEQ ID NO:55, respectively, and

VH and VL arm domains to FX(a), corresponding to SEQ ID NO:923 and SEQ ID NO:927, respectively.

In one embodiment, the bispecific antibody comprises the VH and VL arm domains of FIX(a) corresponding to SEQ ID NO:51 and SEQ ID NO:55, respectively, and

VH and VL arm domains to FX(a), corresponding to SEQ ID NO:907 and SEQ ID NO:911, respectively.

In one embodiment, the bispecific antibody comprises the VH and VL arm domains of FIX(a) corresponding to SEQ ID NO:51 and SEQ ID NO:55, respectively, and

VH and VL arm domains to FX(a), corresponding to SEQ ID NO:731 and SEQ ID NO:735, respectively.

In one embodiment, the bispecific antibody comprises the VH and VL arm domains of FIX(a) corresponding to SEQ ID NO:51 and SEQ ID NO:55, respectively, and

VH and VL arm domains to FX(a), corresponding to SEQ ID NO:915 and SEQ ID NO:919, respectively.

In one embodiment, the bispecific antibody comprises the VH and VL arm domains of FIX(a) corresponding to SEQ ID NO:51 and SEQ ID NO:55, respectively, and

VH and VL arm domains to FX(a), corresponding to SEQ ID NO:931 and SEQ ID NO:935, respectively.

In one embodiment, the bispecific antibody comprises the VH and VL arm domains of FIX(a) corresponding to SEQ ID NO:51 and SEQ ID NO:55, respectively, and

VH and VL arm domains to FX(a), corresponding to SEQ ID NO:939 and SEQ ID NO:943, respectively.

In one embodiment, the bispecific antibody comprises the VH and VL arm domains of FIX(a) corresponding to SEQ ID NO:51 and SEQ ID NO:55, respectively, and

VH and VL arm domains to FX(a), corresponding to SEQ ID NO:963 and SEQ ID NO:967, respectively.

In one embodiment, the bispecific antibody comprises the VH and VL arm domains of FIX(a) corresponding to SEQ ID NO:51 and SEQ ID NO:55, respectively, and

VH and VL arm domains to FX(a), corresponding to SEQ ID NO:971 and SEQ ID NO:975, respectively.

In one embodiment, the bispecific antibody comprises the VH and VL arm domains of FIX(a) corresponding to SEQ ID NO:51 and SEQ ID NO:55, respectively, and

VH and VL arm domains to FX(a), corresponding to SEQ ID NO:947 and SEQ ID NO:951, respectively.

In one embodiment, the bispecific antibody comprises the VH and VL arm domains of FIX(a) corresponding to SEQ ID NO:51 and SEQ ID NO:55, respectively, and

VH and VL arm domains to FX(a), corresponding to SEQ ID NO:739 and SEQ ID NO:743, respectively.

In one embodiment, the bispecific antibody comprises the VH and VL arm domains of FIX(a) corresponding to SEQ ID NO:51 and SEQ ID NO:55, respectively, and

VH and VL arm domains to FX(a), corresponding to SEQ ID NO:955 and SEQ ID NO:959, respectively.

In one embodiment, the bispecific antibody comprises the VH and VL arm domains of FIX(a) corresponding to SEQ ID NO:51 and SEQ ID NO:55, respectively, and

VH and VL arm domains to FX(a), corresponding to SEQ ID NO:979 and SEQ ID NO:983, respectively.

In one embodiment, the bispecific antibody comprises the VH and VL arm domains of FIX(a) corresponding to SEQ ID NO:51 and SEQ ID NO:55, respectively, and

VH and VL arm domains to FX(a), corresponding to SEQ ID NO:987 and SEQ ID NO:991, respectively.

In one embodiment, the bispecific antibody comprises the VH and VL arm domains of FIX(a) corresponding to SEQ ID NO:51 and SEQ ID NO:55, respectively, and

VH and VL arm domains to FX(a), corresponding to SEQ ID NO:1011 and SEQ ID NO:1015, respectively.

In one embodiment, the bispecific antibody comprises the VH and VL arm domains of FIX(a) corresponding to SEQ ID NO:51 and SEQ ID NO:55, respectively, and

VH and VL arm domains to FX(a), corresponding to SEQ ID NO:1019 and SEQ ID NO:1023, respectively.

In one embodiment, the bispecific antibody comprises the VH and VL arm domains of FIX(a) corresponding to SEQ ID NO:51 and SEQ ID NO:55, respectively, and

VH and VL arm domains to FX(a), corresponding to SEQ ID NO:995 and SEQ ID NO:999, respectively.

In one embodiment, the bispecific antibody comprises the VH and VL arm domains of FIX(a) corresponding to SEQ ID NO:51 and SEQ ID NO:55, respectively, and

VH and VL arm domains to FX(a), corresponding to SEQ ID NO:747 and SEQ ID NO:751, respectively.

In one embodiment, the bispecific antibody comprises the VH and VL arm domains of FIX(a) corresponding to SEQ ID NO:51 and SEQ ID NO:55, respectively, and

VH and VL arm domains to FX(a), corresponding to SEQ ID NO:1003 and SEQ ID NO:1007, respectively.

In one embodiment, the bispecific antibody comprises the VH and VL arm domains of FIX(a) corresponding to SEQ ID NO:51 and SEQ ID NO:55, respectively, and

VH and VL arm domains to FX(a), corresponding to SEQ ID NO:1027 and SEQ ID NO:1031, respectively.

In one embodiment, the bispecific antibody comprises the VH and VL arm domains of FIX(a) corresponding to SEQ ID NO:51 and SEQ ID NO:55, respectively, and

VH and VL arm domains to FX(a), corresponding to SEQ ID NO:1051 and SEQ ID NO:1055, respectively.

In one embodiment, the bispecific antibody comprises the VH and VL arm domains of FIX(a) corresponding to SEQ ID NO:51 and SEQ ID NO:55, respectively, and

VH and VL arm domains to FX(a), corresponding to SEQ ID NO:1035 and SEQ ID NO:1039, respectively.

In one embodiment, the bispecific antibody comprises the VH and VL arm domains of FIX(a) corresponding to SEQ ID NO:51 and SEQ ID NO:55, respectively, and

VH and VL arm domains to FX(a), corresponding to SEQ ID NO:1059 and SEQ ID NO:1063, respectively.

In one embodiment, the bispecific antibody comprises the VH and VL arm domains of FIX(a) corresponding to SEQ ID NO:51 and SEQ ID NO:55, respectively, and

VH and VL arm domains to FX(a), corresponding to SEQ ID NO:1043 and SEQ ID NO:1047, respectively.

In one embodiment, the bispecific antibody comprises the VH and VL arm domains of FIX(a) corresponding to SEQ ID NO:51 and SEQ ID NO:55, respectively, and

VH and VL arm domains to FX(a), corresponding to SEQ ID NO:1067 and SEQ ID NO:1071, respectively.

In one embodiment, the bispecific antibody comprises the VH and VL arm domains of FIX(a) corresponding to SEQ ID NO:51 and SEQ ID NO:55, respectively, and

VH and VL arm domains to FX(a), corresponding to SEQ ID NO:1075 and SEQ ID NO:1079, respectively.

In one embodiment, the bispecific antibody comprises the VH and VL arm domains of FIX(a) corresponding to SEQ ID NO:51 and SEQ ID NO:55, respectively, and

VH and VL arm domains to FX(a), corresponding to SEQ ID NO:1099 and SEQ ID NO:1103, respectively.

In one embodiment, the bispecific antibody comprises the VH and VL arm domains of FIX(a) corresponding to SEQ ID NO:51 and SEQ ID NO:55, respectively, and

VH and VL arm domains to FX(a), corresponding to SEQ ID NO:755 and SEQ ID NO:759, respectively.

In one embodiment, the bispecific antibody comprises the VH and VL arm domains of FIX(a) corresponding to SEQ ID NO:51 and SEQ ID NO:55, respectively, and

VH and VL arm domains to FX(a), corresponding to SEQ ID NO:1107 and SEQ ID NO:1111, respectively.

In one embodiment, the bispecific antibody comprises the VH and VL arm domains of FIX(a) corresponding to SEQ ID NO:51 and SEQ ID NO:55, respectively, and

VH and VL arm domains to FX(a), corresponding to SEQ ID NO:1083 and SEQ ID NO:1087, respectively.

In one embodiment, the bispecific antibody comprises the VH and VL arm domains of FIX(a) corresponding to SEQ ID NO:51 and SEQ ID NO:55, respectively, and

VH and VL arm domains to FX(a), corresponding to SEQ ID NO:1115 and SEQ ID NO:1119, respectively.

In one embodiment, the bispecific antibody comprises the VH and VL arm domains of FIX(a) corresponding to SEQ ID NO:51 and SEQ ID NO:55, respectively, and

VH and VL arm domains to FX(a), corresponding to SEQ ID NO:1091 and SEQ ID NO:1095, respectively.

In one embodiment, the bispecific antibody comprises the VH and VL arm domains of FIX(a) corresponding to SEQ ID NO:51 and SEQ ID NO:55, respectively, and

VH and VL arm domains to FX(a), corresponding to SEQ ID NO:1123 and SEQ ID NO:1127, respectively.

In one embodiment, the bispecific antibody comprises the VH and VL arm domains of FIX(a) corresponding to SEQ ID NO:51 and SEQ ID NO:55, respectively, and

VH and VL arm domains to FX(a) corresponding to SEQ ID NO:1131 and SEQ ID NO:1135, respectively.

In one embodiment, the bispecific antibody comprises the VH and VL arm domains of FIX(a) corresponding to SEQ ID NO:51 and SEQ ID NO:55, respectively, and

VH and VL arm domains to FX(a) corresponding to SEQ ID NO:1155 and SEQ ID NO:1159, respectively.

In one embodiment, the bispecific antibody comprises the VH and VL arm domains of FIX(a) corresponding to SEQ ID NO:51 and SEQ ID NO:55, respectively, and

VH and VL arm domains to FX(a), corresponding to SEQ ID NO:1163 and SEQ ID NO:1167, respectively.

In one embodiment, the bispecific antibody comprises the VH and VL arm domains of FIX(a) corresponding to SEQ ID NO:51 and SEQ ID NO:55, respectively, and

VH and VL arm domains to FX(a) corresponding to SEQ ID NO:1139 and SEQ ID NO:1143, respectively.

In one embodiment, the bispecific antibody comprises the VH and VL arm domains of FIX(a) corresponding to SEQ ID NO:51 and SEQ ID NO:55, respectively, and

VH and VL arm domains to FX(a) corresponding to SEQ ID NO:1171 and SEQ ID NO:1175, respectively.

In one embodiment, the bispecific antibody comprises the VH and VL arm domains of FIX(a) corresponding to SEQ ID NO:51 and SEQ ID NO:55, respectively, and

VH and VL arm domains to FX(a), corresponding to SEQ ID NO:1147 and SEQ ID NO:1151, respectively.

In one embodiment, the bispecific antibody comprises the VH and VL arm domains of FIX(a) corresponding to SEQ ID NO:51 and SEQ ID NO:55, respectively, and

VH and VL arm domains to FX(a), corresponding to SEQ ID NO:1179 and SEQ ID NO:1183, respectively.

In one embodiment, the bispecific antibody comprises the VH and VL arm domains of FIX(a) corresponding to SEQ ID NO:51 and SEQ ID NO:55, respectively, and

VH and VL arm domains to FX(a), corresponding to SEQ ID NO:1187 and SEQ ID NO:1191, respectively.

In one embodiment, the bispecific antibody comprises the VH and VL arm domains of FIX(a) corresponding to SEQ ID NO:51 and SEQ ID NO:55, respectively, and

VH and VL arm domains to FX(a), corresponding to SEQ ID NO:547 and SEQ ID NO:551, respectively.

In one embodiment, the bispecific antibody comprises the VH and VL arm domains of FIX(a) corresponding to SEQ ID NO:1202 and SEQ ID NO:1206, respectively, and

VH and VL arm domains to FX(a), corresponding to SEQ ID NO:467 and SEQ ID NO:471, respectively.

In one embodiment, the bispecific antibody comprises the VH and VL arm domains of FIX(a) corresponding to SEQ ID NO:1210 and SEQ ID NO:1214, respectively, and

VH and VL arm domains to FX(a), corresponding to SEQ ID NO:467 and SEQ ID NO:471, respectively.

In one embodiment, the bispecific antibody comprises the VH and VL arm domains of FIX(a) corresponding to SEQ ID NO:1218 and SEQ ID NO:1222, respectively, and

VH and VL arm domains to FX(a), corresponding to SEQ ID NO:467 and SEQ ID NO:471, respectively.

In one embodiment, the bispecific antibody comprises the VH and VL arm domains of FIX(a) corresponding to SEQ ID NO:1226 and SEQ ID NO:1230, respectively, and

VH and VL arm domains to FX(a), corresponding to SEQ ID NO:467 and SEQ ID NO:471, respectively.

In one embodiment, the bispecific antibody comprises the VH and VL arm domains of FIX(a) corresponding to SEQ ID NO:1234 and SEQ ID NO:1238, respectively, and

VH and VL arm domains to FX(a), corresponding to SEQ ID NO:467 and SEQ ID NO:471, respectively.

In one embodiment, the bispecific antibody comprises the VH and VL arm domains of FIX(a) corresponding to SEQ ID NO:1242 and SEQ ID NO:1246, respectively, and

VH and VL arm domains to FX(a), corresponding to SEQ ID NO:467 and SEQ ID NO:471, respectively.

In one embodiment, the paratope of an anti-FIX(a) antibody or antigen binding fragment thereof of the present invention comprises amino acid residues H30, D31, W53, D56, S102, S104, Y106 and N107 in the heavy chain variable domain (SEQ ID NO:67) and residues Y91 and S92 in the light chain variable domain (SEQ ID NO:71).

In one embodiment, an anti-FIX(a) antibody or antigen binding fragment thereof of the present invention comprises one, two or three amino acid substitutions or deletions within the group of paratope amino acid residues H30, D31, W53, D56, S102, S104, Y106 and N107 in the variable heavy chain domain (SEQ ID NO:67) and residues Y91 and S92 in the light chain variable domain (SEQ ID NO:71).

In another embodiment, the paratope of the anti-FIX(a) antibody or antigen binding fragment thereof of the present invention comprises amino acid residues D30, D31, W53, S102, S104 and N107 in the heavy chain variable domain (SEQ ID NO:35) and residues Y91 and S92 in light chain variable domain (SEQ ID NO:39).

In another embodiment, the anti-FIX(a) antibody of the present invention contains one, two or three amino acid substitutions or deletions within the group of paratope amino acid residues: D30, D31, W53, S102, S104 and N107 in the heavy chain variable domain (SEQ ID NO :35) and residues Y91 and S92 in the light chain variable domain (SEQ ID NO:39).

In one embodiment, the CDR sequences of an antibody or antigen binding fragment thereof of the present invention can be described by the paratope amino acid residues of the anti-FIX(a) antibody that are part of these CDRs.

In one such embodiment, the anti-FIX(a) antibody paratope CDRs are:

where paratope amino acid residues are in bold and X represents a naturally occurring amino acid residue.

In another such embodiment, the anti-FIX(a) antibody paratope CDRs are:

where paratope amino acid residues are in bold and X represents a naturally occurring amino acid residue.

In another such embodiment, the anti-FIX(a) antibody paratope CDRs are:

CDR1 VH (based on SEQ ID NO:52): DXXXX;

CDR2 VH (based on SEQ ID NO:53): XXXWXXXXXXXXXXXXXX;

CDR3 VH (based on SEQ ID NO:54): XXXSXSXYNXXXX;

CDR1 VL (based on SEQ ID NO:56): XXXXXXXXXXX;

CDR2 VL (based on SEQ ID NO:57): XXXXXXX;

CDR3 VL (based on SEQ ID NO:58): XXYSXXXXX;

where paratope amino acid residues are in bold and X represents a naturally occurring amino acid residue.

In one embodiment, the paratope of the anti-FX(a) antibody of the present invention contains residues K23, S25, G26, Y27, F29, W33, D52, S54, D55, F57, S77, H100, Y101, Y102, N103 and S104 in the variable domain heavy chain (SEQ ID NO:467) and residues V29, S30, S31, Y33, Y50, Q52, S54, R55, R57 and D94 in the light chain variable domain (SEQ ID NO:471).

In another embodiment, the anti-FX(a) antibody of the present invention contains one, two or three amino acid substitutions or deletions within the group of paratope residues K23, S25, G26, Y27, F29, W33, D52, S54, D55, F57, S77, H100, Y101, Y102, N103 and S104 in the heavy chain variable domain (SEQ ID NO:467) and residues V29, S30, S31, Y33, Y50, Q52, S54, R55, R57 and D94 in the light chain variable domain (SEQ ID NO:471).

In another embodiment, the paratope of the anti-FX(a) antibody of the present invention contains residues K23, G24, S25, G26, Y27, W33, D52, S54, D55, Y57, S77, L99, H100, Y101, Y102, N103 and S104 in the heavy chain variable domain (SEQ ID NO:483) and residues S30, S31, Y33, Y50, Q52, S54, R55, R57, Y92 and D94 in the light chain variable domain (SEQ ID NO:487).

In another embodiment, the anti-FX(a) antibody of the present invention contains one, two or three amino acid substitutions or deletions within the group of paratope residues K23, G24, S25, G26, Y27, W33, D52, S54, D55, Y57, S77, L99, H100, Y101, Y102, N103 and S104 in the heavy chain variable domain (SEQ ID NO:483) and residues S30, S31, Y33, Y50, Q52, S54, R55, R57, Y92 and D94 in the light chain variable domain ( SEQ ID NO:487).

In one embodiment, the CDR sequences of such an antibody can be described by the anti-FX(a) antibody paratope amino acid residues that are part of those CDRs.

In one such embodiment, the anti-FX(a) antibody paratope CDRs are

where paratope amino acid residues are in bold and X represents a naturally occurring amino acid residue.

In another such embodiment, the anti-FX(a) antibody paratope CDRs are:

where paratope amino acid residues are in bold and X represents a naturally occurring amino acid residue.

In one embodiment, the antibody of the present invention is a multispecific antibody or antigen binding fragment thereof capable of stimulating the enzymatic activity of FIXa against FX, comprising a first antigen binding site capable of binding to FIX (SEQ ID NO:1) and/or an activated form of FIXa thereof, and a second antigen-binding region capable of binding to FX (SEQ ID NO:2) or an activated form thereof (FXa).

In one such embodiment, the first antigen binding region comprises a paratope containing amino acid residues D30, D31, W53, S102, S104 and N107 in the heavy chain variable domain (SEQ ID NO:35) and amino acid residues Y91 and S92 in the light chain variable domain (SEQ ID NO:39), and the second antigen-binding region contains a paratope containing amino acid residues K23, G24, S25, G26, Y27, W33, D52, S54, D55, Y57, S77, L99, H100, Y101, Y102, N103 and S104 in heavy chain variable domain (SEQ ID NO:483) and amino acid residues S30, S31, Y33, Y50, Q52, S54, R55, R57, Y92 and D94 in the light chain variable domain (SEQ ID NO:487).

In one such embodiment, the first antigen binding region comprises a paratope comprising amino acid residues H30, D31, W53, D56, S102, S104, Y106 and N107 in the heavy chain variable domain (SEQ ID NO:67) and amino acid residues Y91 and S92 in the variable domain light chain (SEQ ID NO:71), and the second antigen binding region comprises a paratope containing amino acid residues K23, G24, S25, G26, Y27, W33, D52, S54, D55, Y57, S77, L99, H100, Y101, Y102, N103 and S104 in the heavy chain variable domain (SEQ ID NO:483) and amino acid residues S30, S31, Y33, Y50, Q52, S54, R55, R57, Y92 and D94 in the light chain variable domain (SEQ ID NO:487).

In one such embodiment, the first antigen binding region comprises a paratope comprising amino acid residues H30, D31, W53, D56, S102, S104, Y106 and N107 in the heavy chain variable domain (SEQ ID NO:67) and amino acid residues Y91 and S92 in the variable domain light chain (SEQ ID NO:71), and the second antigen binding region comprises a paratope containing amino acid residues K23, S25, G26, Y27, F29, W33, D52, S54, D55, F57, S77, H100, Y101, Y102, N103 and S104 in the heavy chain variable domain (SEQ ID NO:467) and amino acid residues V29, S30, S31, Y33, Y50, Q52, S54, R55, R57 and D94 in the light chain variable domain (SEQ ID NO:471).

In one such embodiment, the first antigen binding region comprises a paratope containing amino acid residues D30, D31, W53, S102, S104 and N107 in the heavy chain variable domain (SEQ ID NO:35) and amino acid residues Y91 and S92 in the light chain variable domain (SEQ ID NO:39), and the second antigen binding region contains a paratope containing amino acid residues K23, S25, G26, Y27, F29, W33, D52, S54, D55, F57, S77, H100, Y101, Y102, N103 and S104 in the variable domain heavy chain (SEQ ID NO:467) and amino acid residues V29, S30, S31, Y33, Y50, Q52, S54, R55, R57 and D94 in the light chain variable domain (SEQ ID NO:471).

In one such embodiment, the first antigen binding region comprises a paratope comprising amino acid residues H30, D31, W53, S102, S104, Y106 and N107 in the heavy chain variable domain (SEQ ID NO:51) and amino acid residues Y91 and S92 in the light chain variable domain (SEQ ID NO:55), and the second antigen binding region comprises a paratope containing amino acid residues K23, S25, G26, Y27, F29, W33, D52, S54, D55, F57, S77, H100, Y101, Y102, N103 and S104 in heavy chain variable domain (SEQ ID NO:467) and amino acid residues V29, S30, S31, Y33, Y50, Q52, S54, R55, R57 and D94 in the light chain variable domain (SEQ ID NO:471).

In one embodiment, the antibody is a bispecific antibody capable of binding to FIX(a) and FX(a).

In one embodiment, an antibody of the present invention is capable of binding FIXa with a higher affinity than the affinity with which it binds FIX.

In one embodiment, the antibody of the present invention is capable of increasing the enzymatic activity of FIXa against FX.

In one such embodiment, an antibody of the present invention is capable of increasing the FX enzymatic activity of FIXa as measured in an FXa production assay using the monovalent single-arm antibodies described herein.

In one embodiment, an antibody of the present invention is capable of increasing the FX enzymatic activity of FIXa as measured in an FXa production assay using the bivalent antibodies described herein.

In one embodiment, the multispecific antibodies, such as bispecific antibodies, of the present invention do not interfere with the effects of FVIII, such as recombinant FVIII, administered to a patient suffering from hemophilia A when the antibodies are used in clinically relevant doses for the treatment of hemophilia A.

In one embodiment, the antibody of the present invention is not the anti-FIX antibody CLB-FIX 13, which is described in Rohlena et al. (2003) J Biol. Chem. 278(11):9394–9401. In one embodiment, the antibody of the present invention is not an anti-FIX HIX-1 (mouse IgG1) antibody (Merck KGaA, SigmaAldrich). In one embodiment, the antibody or antigen binding fragment thereof of the present invention is not an anti-FIX antibody AHIX-5041 (IgG1) (Haematologic Technologies, Inc.).

In one embodiment, the antibody or antigen binding fragment thereof of the present invention has reduced immunogenicity compared to prior art procoagulant antibodies.

In a preferred embodiment, the antibodies of the present invention, unless otherwise indicated or contrary to context, are expressed in IgG4/kappa format.

For the arm to FIX(a), the heavy chain constant domain regions ( _CH1 - _CH2 - _CH3 ) were derived from human IgG4 with the S228P substitution (EU numbering) and truncation of the C-terminal lysine:

In one embodiment, for the arm to FX(a), the heavy chain constant domain regions ( _CH1 - _CH2 - _CH3 ) were derived from human IgG4 with the S228P substitution and two additional substitutions, F405L and R409K (EU numbering ), in the _CH 3 domain to facilitate heavy chain heterodimerization (described in example 4) and with truncation of the C-terminal lysine:

In this case, the light chain constant region (CL) was the human kappa chain:

RTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC (SEQ ID NO:1197).

In another embodiment, antibodies can also be expressed in IgG4 format, wherein the heavy chain constant domain regions (CH ₁ -C _H 2-C _H 3) for the FIX(a) arm carry the S228P, F405L and R409K substitutions and wherein the regions The heavy chain constant domains for the arm to FX(a) carry the S228P substitution, with or without deletion of the C-terminal lysine.

In one embodiment, antibodies can also be expressed in IgG1/kappa format. In this case, the heavy chain constant domain regions of the arm to FIX(a) are human IgG1 with F405L, with the C-terminal lysine truncated:

In this case, the regions of the heavy chain constant domain of the arm to FX(a) are human IgG1 with K409R, with a truncation of the C-terminal lysine:

Antibodies can also be expressed in IgG1 format, wherein the heavy chain constant domain regions (CH ₁ -C _H 2-C _H 3) for the FIX(a) arm carry the K409R substitution and wherein the heavy chain constant domain regions for the FX arm (a) carry the F405L substitution, with or without deletion of the C-terminal lysine.

The constant domain regions may further contain additional substitutions or other modifications, for example, to modulate effector functions, half-life or other properties.

The present invention also provides kits that contain the antibodies or antigen-binding fragments thereof disclosed herein, suitable for the treatment described herein. In some embodiments, the kit includes: (i) an antibody, such as a bispecific antibody or antigen binding fragment thereof, pharmaceutical composition, nucleic acid, vector, or cell (e.g., host cell) disclosed herein, or a combination thereof and (ii) instructions for use. One of ordinary skill in the art will readily appreciate that the antibodies, bispecific molecules (e.g., bispecific antibodies), pharmaceutical compositions, nucleic acids, vectors, or cells (e.g., host cell) disclosed herein, or combinations thereof, can be readily included in one of the established formats kits that are well known in the art.

Examples

List of abbreviations

CAN: acetonitrile bimAb: bispecific monoclonal antibody CDR: complementarity determining region EGR-CK: EGR-chloromethylketone LC-MS: liquid chromatography/mass spectrometry FACS: fluorescence activated cell sorting FIX: blood clotting factor IX FIXa: blood clotting factor IXa FX: blood clotting factor X FXa: coagulation factor Xa HA: hemophilia A HA-PPP: human platelet-poor plasma with induced HA HA-PRP: human platelet-rich plasma with HA-induced hFIXa: human blood clotting factor IXa ITC: isothermal titration calorimetry MACS: sorting of magnetically activated cells OA: one-armed PCR: polymerase chain reaction SPR: surface plasmon resonance

References to ACE910 should be understood to refer to an antibody having an amino acid sequence that is identical to the sequence of ACE910.

Example 1. Development of antibodies to FIX(a) and to FX(a)

The FIX(a) and FX(a) binding antibodies disclosed herein were identified using various antibody development methods. To generate a diverse set of antibodies, immunization procedures were performed in mice and rabbits, and phage display and Adimab yeast-based antibody expression platforms were used.

Adimab Yeast-Based Antibody Platform

The Adimab platform is a yeast antibody expression system housing a library of fully human antigen-naïve IgG1/kappa antibodies with a diversity of 10 ¹⁰ . The antibody selection process was carried out using MACS and FACS based methods, which allow monitoring of the applied selection criteria in real time. Since selection procedures are based on MACS and FACS, labeled antigens (eg, biotin) were necessary. Selection operations were performed using biotin-labeled active site inhibited hFIXa (FIXa-EGR-biotin) or antibody-mediated immobilization of hFIXa. The hits were assessed for binding using biolayer interferometry (Octet ForteBio system).

Phage display

The antibody phage display platform used is a proprietary display library with fully human Fabs. The library size is 10 ¹⁰ and was generated through a combinatorial approach using chemical synthesis of the light chain and heavy chain CDR1 and CDR2, complemented by PCR amplification of the heavy chain CDR3 from human peripheral blood mononuclear cells. To maximize epitope diversity, various panning strategies have been explored, including panning using biotinylated FIXa-EGR, FX, active site inhibited FXa, or antigen capture using anti-FIXa antibodies. Initial hits were identified using phage ELISA. Following sequence analysis, unique hits were cloned and recombinantly expressed as IgG1 antibodies and ranked using SPR (Biacore) or biolayer interferometry (Octet ForteBio system).

In vivo platforms

Mice and rabbits were used to generate antibodies using in vivo platforms. To generate antibodies to FIX/FIXa, mice or rabbits were immunized with FIXa, FIXa-EGR, or human FIX using standard protocols. Spleen cells obtained from mice were fused with myeloma cells using standard techniques, and the resulting hybridoma supernatants containing antibodies were screened for binding to FIXa using ELISA. FIXa-binding rabbit B cells were single-cell sorted using FACS by gating on cells binding random biotinylated FIXa-EGR (detected with a streptavidin-conjugated fluorophore). Sorted rabbit B cells were cultured for seven days in 384-well plates using feeder cells and splenocyte conditioned media before screening against FIXa in ELISA. Rabbit B cells and mouse hybridoma clones expressing FIXa-binding antibody hits were either used for VH/VL sequencing followed by recombinant expression (in the case of rabbit or hybridoma-derived mAbs) or further expanded to produce mAbs (mouse hybridomas ).

To generate antibodies to FX, mice and rabbits were immunized with FX using standard protocols. Rabbit B cells were isolated by FACS-based single cell sorting and using randomly biotinylated FX (detected using a streptavidin-conjugated fluorophore), with spleen cells obtained from immunized mice used for routine hybridoma formation. The resulting antibody-producing mouse B cell clones or hybridomas were screened for FX binding using ELISA and Octet ForteBio systems. Rabbit B cell clones or mouse hybridomas expressing antibody hits were either used for VH/VL sequencing followed by recombinant expression (in the case of rabbit or hybridoma-derived mAbs) or further expanded to produce mAbs (mouse hybridomas).

Sequencing of hybridoma-derived antibodies

Anti-FIXa and anti-FX antibodies produced by the hybridomas were sequenced and expressed in HEK293 cells using standard techniques. Expressed antibodies were assessed for antigen binding using Octet ForteBio systems.

Total RNA was extracted from antibody-producing clones, and DNA sequences encoding the variable domains ( _VH and _VL ) were amplified using RT-PCR. The V _H and V _L sequences were determined and introduced into a pTT-based mammalian expression vector (Durocher et al (2002) Nucleic Acid Res. 30:E9) or into a pcDNA3.4 mammalian expression vector (Invitrogen) containing the DNA sequences , encoding the constant region of the antibody. For mAb expression vectors pTT/pcDNA3.4, DNA sequences V _H and V _L were inserted in frame with DNA sequences encoding human IgG1 or IgG ₄ constant regions with S228P (CH _{1C H} 2C _H 3, optionally with additional amino acid substitutions and deletions, for example substitutions in the C _H 3 domain and deletion of the C-terminal lysine) or human C _L kappa chain, respectively. For the corresponding expression vectors pTT/pcDNA3.4 for Fab, the V _H DNA sequences were brought in frame with the DNA sequences encoding human C _H 1 IgG ₄ .

Example 2. Recombinant expression of antibodies and Fab fragments of antibodies

Antibodies and antibody Fab fragments were expressed using transient transfection of HEK293 cell suspension (293Expi, Invitrogen), essentially following the manufacturer's instructions. Typically, 293Expi cells were subcultured every 3 to 4 days in Expi293F expression medium (Invitrogen, cat. no. A1435104) supplemented with 1% P/S (GIBCO, cat. no. 15140-122). Expi293F cells were transfected at a cell density of 2.5–3 million/ml using Expifectamine. For each liter of Expi293F cells, transfection was carried out by diluting a total of 1 mg of plasmid DNA (plasmids with V _{H -CH} 1 (in the case of Fab) or V _{H -CH} 1-C _H 2-C _H 3 (in the case of mAb) and LC in a 1:1 ratio) in 50 ml of Optimem (GIBCO, catalog number 51985-026, dilution A) and by diluting 2.7 ml of Expifectamine in 50 ml of Optimem (dilution B). For joint transfections with the production of Fab and mAb, plasmids with V _H -C _H 1 and LC (Fab) and plasmids with V _H -C _H 1-C _H 2-C _H 3 and LC (mAb) were used, respectively, in a 1:1 ratio . Dilutions A and B were mixed and incubated at room temperature for 10–20 minutes. The transfection mixture was then added to Expi293F cells and the cells were incubated at 37°C in a humidified rotating incubator (85–125 rpm). One day after transfection, 5 ml of ExpiFectamine 293 transfection enhancer 1 and 50 ml of ExpiFectamine 293 transfection enhancer 2 were added to transfected cells. Cell culture supernatants were typically collected 4–5 days after transfection by centrifugation followed by filtration.

Example 3 Purification and Characterization of Fab and Antibodies

All purification steps were carried out at 4°C. At laboratory scale, Milli-Q water was used to prepare the buffer. An Aglient 1100 HPLC system was used for SE-HPLC analysis. Aggregation and LC/MS results were assessed as quality control.

Fab capture was performed using HiTrap protein G HP affinity chromatography with binding buffer in 1× PBS (10 mM Na2HPO4, 1.8 mM KH2PO4, 137 mM NaCl, 2.7 mM KCl), pH 7.4. One-step elution was performed with 0.1 M glycine, pH 2.8. Desalting of the final product was accomplished by passing it through a 52 mL GE Hiprep 16 desalting column in formulation buffer (25 mM HEPES, 150 mM NaCl) pH 7.4 and concentrated using a centrifugal ultrafilter (30 kDa cutoff) for storage at -80°C.

SDS-PAGE and size exclusion chromatography (SE-HPLC) analysis were performed to assess the quality of purified Fab. Batches that did not meet quality standards (eg, <95% monomers by SE-HPLC) were further purified using size exclusion chromatography. LC/MS was performed to verify Fab protein identity. The molecular weight (MW) values of all Fabs were shown to be consistent with the theoretical MW of the heavy chain and light chain, respectively.

Antibody Purification and Characterization

Antibody purification was performed by affinity chromatography using MabSelect SuRe protein A resins (GE Healthcare, catalog number 17-5438-01). For small-scale antibody production, Protein A-based purification was performed in 96-well plates, while for larger-scale production, an ÄktaExplorer chromatography system (GE Healthcare, catalog number 18-1112-41) was used. The buffer systems used for the affinity purification step were: 1) equilibration buffer consisting of 20 mM Na phosphate, pH 7.2, 150 mM NaCl, 2) elution buffer consisting of 10 mM formic acid, pH 3.5, and 3) pH adjustment buffer consisting of 0.4 M Na phosphate, pH 9.0. Cell supernatants were applied directly to a pre-equilibrated MabSelect SuRe column without any adjustments. The column was washed with approximately 10 column volumes of equilibration buffer, and antibodies were eluted isocratically in approximately 2–5 column volumes of elution buffer. The pH of the pooled fractions was adjusted to neutral using the described pH adjustment buffer immediately after elution.

The characteristics of the purified antibodies were determined using various methods such as SDS-PAGE/Coomassie, size exclusion liquid chromatography (SE-HPLC) and liquid chromatography/mass spectrometry (LC-MS) assays. SDS-PAGE/Coomassie analysis was performed using 4–12% Bis-Tris NuPage gels (Invitrogen, cat. no. NP0321BOX). In this case, the expected light chain and heavy chain components are shown for all antibodies. Intact molecular weight determination was performed using a liquid chromatography/electrospray ionization time-of-flight mass spectrometry setup on an Agilent 6210 instrument and a MassPREP desalting column (Waters, cat. no. USRM10008656). The buffer system used was an equilibration buffer consisting of LC-MS grade 0.1% formic acid in H ₂ O and an elution buffer consisting of LC-MS grade 0.1% formic acid in ACN. Assays were performed with and without N-glycosidase F (Roche Diagnostics, catalog number 11365177001) and a reducing agent (i.e., mercaptoethanol or DTT). For all antibodies, expected intact molecular weights are shown according to the sequence and one heavy chain N-glycan. Purity was determined based on SE-HPLC. Final protein purity was analyzed based on the SE-HPLC setup on an Agilent LC 1100/1200 system using a BIOSep-SEC-S3000 300 x 7.8 mm column (Phenomenex, cat. no. 00H-2146-K0) and running buffer, consisting of 200 mM Na phosphate, pH 6.9, 300 mM NaCl and 10% isopropanol. UV280 and fluorescence detectors (280 nm excitation/354 nm emission) were used for detection. Antibodies eluted as single symmetrical peaks with retention times reflecting antibody size. All purity estimates were between 95–99% for different antibodies. A NanoDrop spectrophotometer (Thermo Scientific) was used to measure final protein concentrations along with specific extinction coefficients for each antibody.

Example 4 Bispecific Antibodies Produced by In Vitro Assembly

Bispecific antibodies were prepared by in vitro assembly of the first and second antibodies using the Duobody ^® (Genmab) method described (Labrijn et al. PNAS 2013, vol. 110, pp. 5145–5150) for human IgG1-based bispecific antibodies and using a slightly modified version in the case of human IgG4 bispecific antibodies, as described in detail below.

In the case of IgG1, the heavy chain constant region of the first antibody is human IgG1 K409R (anti-FIX/FIXa antibody), and the heavy chain constant region of the second antibody is human IgG1 F405L (anti-FX/FXa antibody). IgG1 may be a variant of IgG1 with reduced effector functions, as mentioned previously.

In the case of human IgG4, the heavy chain constant region of the first antibody is IgG4 to S228P (anti-FIX/FIXa antibody), and the heavy chain constant region of the second antibody is IgG4 to S228P, F405L+R409K (anti-FX antibody). Two starting antibodies are prepared as described in Examples 1-3. The Fab arm exchange reaction is carried out in HEPES buffer (pH 7.4) under reducing conditions using 75 mM 2-mercaptoethylamine (2-MEA) and incubation at 30°C for 4 hours.

Example 5. Preparation of monovalent (single-armed) antibodies

To avoid any potential avidity effects associated with traditional monospecific and bivalent antibodies, for example, in the FXa production assays (Example 12) and in certain SPR-based experiments (Examples 10 and 11), the monovalent single-arm (OA) antibody format described in Martens et al.: A Novel One-Armed Anti-c-Met Antibody Inhibits Glioblastoma Growth In Vivo. Clin. Cancer Res. 12, 6144–6152 (2006), where the full heavy chain, a truncated heavy chain (without the Fab region) and a light chain are co-expressed. Instead of co-expression of the three chains described in Martens et al., in the present invention monovalent antibodies were produced using the ^Duobody® principle described for bispecific antibodies (Example 4). Here, monovalent antibodies were prepared by mixing a full monospecific and bivalent antibody and a truncated heavy chain dimer (formally derived from the full antibody by removing the Fab region) and allowing chain exchange to occur under the same experimental conditions as described in Example 4. To form a monovalent antibody the antibody and truncated heavy chain dimer are required to carry the appropriate complementary mutations to promote heterodimerization, i.e., F405L/K409R for human IgG1 and F405L+R409K/WT for human IgG4, as described in Example 4.

In the case of monovalent antibodies of the IgG1 subtype, the heavy chain truncation may extend from the N-terminus to a position between Cys 220 and the upper hinge Cys 226 (EU numbering). A specific example of a truncated human IgG1 heavy chain is a chain in which residues 1-220 are truncated.

In the case of monovalent antibodies of the human IgG4 subtype, the heavy chain truncation may extend from the N-terminus to a position between Cys 200 and the upper hinge Cys 226 (EU numbering). A specific example of a truncated human IgG4 heavy chain is a chain in which residues 1-214 are truncated.

Example 7a. Sorting by groups of stimulating antibodies to FIX/FIXa

Antibodies capable of stimulating the enzymatic activity of FIXa against FX were analyzed in batch experiments to determine the binding characteristics of the identified antibodies using the method described below. Both parental antibodies and engineered variants were analyzed and compared with other known antibodies.

Method for sorting antibodies into groups

Group sorting experiments were performed using Octet ForteBio systems (HTX, Red384), based on the principle of biolayer interferometry and equipped with streptavidin sensors (Pall Life Sciences, Menlo Park, CA), and using 8-channel mode. Group sorting assays were performed using a modified tandem mode. Briefly, (1) 370 nM randomly biotinylated human FIXa (biotinylated with NHS-d-biotin from Sigma H1759 and human FIXa obtained from Haematologic Technologies, Essex Junction, Vermont) was captured with streptavidin tips (immersible and readout biosensors, item no. :18-5019, Pall Life Sciences, Menlo Park, CA) for 5 minutes, (2) then 330 nM of the first bivalent anti-FIXa antibody was applied to the streptavidin tips and incubated for 10 minutes until biotinylated FIXa became fully saturated, and (3) then an equimolar solution of 330 nM first antibody and 330 nM second bivalent anti-FIXa antibody was applied under the tips for 5 minutes. This modified tandem regimen, incorporating an equimolar concentration of the first antibody in the second antibody incubation step, was preferred due to the very low affinity (and high koff rates) of some of the antibodies used. Nonspecific binding was assessed by including an unrelated bivalent human IgG4 antibody as the first and second control antibodies. As can be seen from Table 4, which presents the response values at stage (3), three different groups were identified in the analysis, represented by bivalent antibodies to FIXa, 224F3 (mAb01-1582), mAb01-1767 and mAb01-2434 (ACE910 arms to FIX( a)). It is also clear from Table 4 that the engineered antibodies mAb01-9933, mAb01-9978, mAb01-9985 and mAb01-9994 exhibit the same type of group sorting as their parent antibody mAb01-1767 and therefore belong to group B ( as shown in Table 4).

Table 4. Response values according to interferometry

1st antibody 224F3
(group A) mAb01-1767
(group B) mAb01-2434
(group C) hIgG4
(control) 2nd antibody 224F3 0.11 1.60 1.69 2.11 mAb01-1767 0.95 0.02 1.11 1.41 mAb01-2434 0.41 0.49 0.14 0.85 mAb01-9933 0.34 0.02 0.46 0.59 mAb01-9978 0.24 0.01 0.34 0.40 mAb01-9985 0.44 0.02 0.60 0.83 mAb01-9994 0.40 0.01 0.56 0.75 hIgG4 (control) 0.08 -0.02 -0.04 -0.03

As shown in Table 4, human IgG4, which serves as a control antibody, was unable to bind to FIXa when used as the second antibody (last row of Table 4) and did not prevent the second antibody from binding to FIXa when used as the first antibody (last column of Table 4). . 224F3 and mAb01-2434 have self-competitive response values above zero, namely 0.11 and 0.14, respectively, which are still significantly lower than the lowest response values for second antibodies belonging to the other group, for example, 0.24 for mAb01- 9978 ( ^2nd antibody)/224F3 ( ^1st antibody) and 0.34 for mAb01-9978 ( ^2nd antibody)/mAb01-2434 ( ^1st antibody). Some examples of complete binding curves are shown in Figures 4A and 4B (C, D, E and F).

Example 7b. Sorting by groups of stimulating antibodies to FX/FXa

Antibodies to FX(a) were analyzed in batch experiments to determine the binding characteristics of the identified antibodies using the method described below. Both parental antibodies and engineered variants were analyzed and compared with other known antibodies.

Method for sorting antibodies into groups

Group sorting experiments were performed using Octet ForteBio systems (HTX, Red384) equipped with streptavidin sensors (Pall Life Sciences, Menlo Park, CA) and using 8-channel mode (Red384 and HTX). Group sorting assays were performed using a modified tandem mode. Briefly, (1) 363 nM randomly biotinylated human FXa (obtained from Haematologic technologies and biotinylated using NHS-d-biotin) was captured with streptavidin tips for 5 minutes (Immersion and Readout Biosensors, Item No.: 18-5019, Pall Life Sciences, Menlo Park, CA), (2) then 330 nM of the first bivalent anti-FX(a) antibody was applied to the streptavidin tips and incubated for 10 minutes until the biotinylated FXa was completely saturated, and (3) then an equimolar solution of 330 nM of the first antibody and 330 nM of the second bivalent antibody to FX(a) was applied under the tips for 5 minutes. The regimen of including an equimolar concentration of the first antibody during the second antibody incubation step was preferred due to the very low affinity (and high koff rates) of some of the antibodies used. Nonspecific binding was assessed by including an unrelated bivalent human IgG4 antibody as the first and second control antibodies. As can be seen from Table 5, which presents the response values in stage (3), two different groups were identified in the analysis, represented by bivalent antibodies to FX(a), mAb01-2435 (ACE910 arms to FX(a)) and mAb01-6723. It is also clear from Table 5 that the engineered antibodies mAb01-8174 and mAb01-9772 exhibit the same type of group sorting as their parent antibody mAb01-6723 and therefore belong to group 2 (as shown in Table 5).

Some examples of complete binding curves are shown in Figure 5 (A and B).

Table 5. Response values according to interferometry

1st antibody mAb01-2435
(group 1) mAb01-6723
(group 2) hIgG4
(control) 2nd antibody mAb01-2435 -0.05 0.85 2.63 mAb01-6723 0.79 -0.02 2.59 mAb01-8174 0.62 0.05 2.29 mAb01-9772 0.22 -0.01 1.49 hIgG4 (control) -0.08 -0.03 -0.09

Example 8 Crystallization and epitope/paratope mapping of anti-FIX(a) antibodies using X-ray crystallography

Crystallization and epitope/paratope mapping of anti-FIX(a) mAb01-9994

Crystallization

The Fab fragment corresponding to mAb01-9994 was mixed at a 1:1 molar ratio with human factor IXa without the Gla domain (wild type), with inhibited EGR-CK expressed in bacterial cells, lot no. hGDFIXAWTEGR_05 (purchased from Cambridge ProteinWorks), and Crystals of the Fab/FIXa complex were grown using the sessile drop vapor diffusion technique at 18°C. 100 nl of a protein solution containing 5.5 mg/ml of the complex in 20 mM Tris-HC, pH 7.4, 50 mM NaCl and 2.5 mM CaCl ₂ was mixed with 100 nl of 0.1 M bicine, pH 9.0 , 2% (v/v) 1,4-dioxane, 10% PEG 20000 as precipitant and incubated over 60 μL of precipitant.

Diffraction Data Collection

The crystal was cryoprotected by adding 1 μL of precipitant with 20% ethylene glycol to the crystallization drop before flash cooling in liquid nitrogen. Diffraction data were collected at 100K in the Diamond Light Source's i03 synchrotron radiation beam (wavelength 0.9763 Å) using a Pilatus3 6M pixel detector from Dectris. Auto-indexing, data integration and scaling were performed using programs from the XDS package (statistical values of the diffraction data are summarized in Table 6).

Defining and clarifying the structure

The asymmetric unit contains one Fab:FIXa complex, based on Matthews coefficient analysis. The structure was determined by molecular replacement using Phaser implemented in the Phenix software package, using the structure of the predefined Fab:FIXa complex as a search model. The correct amino acid sequence was modeled using COOT, and then the structure was refined using refinement steps in Phenix and manual reconstruction in COOT. The statistical values of the refinements are given in Table 6.

Table 6. Statistical values of collected and updated data

Wavelength (Å) 0.9763 Resolution range (Å) 43.06 - 2.7 (2.797 - 2.7) Space group P4 ₃ 2 ₁ 2 Unit cell (Å, deg.) 87.65 87.65 231.8 90 90 90 Total number of reflections 327518 (33655) Number of unique reflections 25718 (2511) Repeatability 12.7 (13.4) Completeness (%) 99.94 (100.00) Average I/sigma(I) 13.21 (1.28) Wilson's B factor (Å ² ) 77.47 R-merge 0.15 (2.05) R-meas 0.1565 (2.13) R-pim 0.04391 (0.5757) CC1/2 0.998 (0.447) CC* 1 (0.786) Reflections used in refinement 25715 (2511) Reflections used for R-free 968 (93) R-work 0.1978 (0.3407) R-free 0.2494 (0.4171) CC(work) 0.933 (0.554) CC(free) 0.988 (0.575) Number of atoms other than a hydrogen atom 5597 Macromolecules 5540 Ligands 25 Solvent 32 Protein residues 719 RMS(relation) (Å) 0.012 RMS(angles) (deg.) 1.92 Percentage of residues in preferred area according to Ramachandran map (%) 90.24 Percentage of residues in the feasible region according to the Ramachandran map (%) 7.92 Marginal residuals according to Ramachandran map (%) 1.84 Percentage of deviation of side chains from rotamers (%) 0.00 Overlap Index 12.93 Average B-factor value (Å ² ) 82.66 Macromolecules 82.77 Ligands 85.42 Solvent 61.00

Statistical values for the highest resolution shell are shown in parentheses.

Epitope determination for mAb01-9994

The epitope for mAb01-9994, defined as FIX(a) residues characterized by the presence of a heavy atom (i.e., an atom other than a hydrogen atom) within 3.5 Å of the heavy atom in Fab, includes the following residues: L337, R338, T340, K341 and T343 according to SEQ ID NO:1.

Paratope determination in mAb01-9994

The paratope in mAb01-9994, defined as Fab residues characterized by the presence of a heavy atom (i.e., an atom other than a hydrogen atom) at a distance of 3.5 Å from the heavy atom in FIXa, contains residues (sequential numbering): H30, D31, W53, D56, S102, S104, Y106 and N107 in the heavy chain variable domain (SEQ ID NO:67) and residues Y91 and S92 in the light chain variable domain (SEQ ID NO:71).

Residues in bold are located in CDR sequences as determined using the Kabat definition, while the remaining paratope residue H30 (in the heavy chain variable domain) is a framework residue.

Crystallization and epitope/paratope mapping of anti-FIX/FIXa mAb01-9933

Crystallization

The Fab fragment corresponding to mAb01-9933 was mixed at a 1:1 molar ratio with human factor IXa without the Gla domain (wild type), with inhibited EGR-CK expressed in bacterial cells, lot no. hGDFIXAWTEGR_05 (purchased from Cambridge ProteinWorks), and Crystals of the Fab/FIXa complex were grown using the sessile drop vapor diffusion technique at 18°C. 150 nl of a protein solution containing 8.1 mg/ml of the complex in 20 mM Tris-HCl, pH 7.4, 50 mM NaCl and 2.5 mM CaCl ₂ was mixed with 50 nl of 0.1 M Bis-Tris, pH 6 ,5, 20% (wt/vol) PEG 5000 MME as precipitant, and incubated over 60 μl of precipitant.

Diffraction Data Collection

The crystal was cryoprotected by adding 1 μL of precipitant with 20% ethylene glycol to the crystallization drop before flash cooling in liquid nitrogen. Diffraction data were collected at 100K in the Diamond Light Source's i03 synchrotron radiation beam (wavelength 0.9763 Å) using a Pilatus3 6M pixel detector from Dectris. Auto-indexing, data integration and scaling were performed using programs from the XDS package (statistical values of the diffraction data are summarized in Table 7).

Defining and clarifying the structure

The asymmetric unit contains one Fab:FIXa complex, based on Matthews coefficient analysis. The structure was determined by molecular replacement using Phaser implemented in the Phenix software package, using the structure of the predefined Fab:FIXa complex as a search model. The correct amino acid sequence was modeled using COOT, and then the structure was refined using refinement steps in Phenix and manual reconstruction in COOT. The statistical values of the refinements are given in Table 7.

Table 7. Statistical values of collected and updated data

Wavelength (Å) 0.9763 Resolution range (Å) 47.16 - 2.4 (2.486 - 2.4) Space group P 4 ₃ 2 ₁ 2 Unit cell (Å, deg.) 85.7 85.7 225.95 90 90 90 Total number of reflections 433016 (39929) Number of unique reflections 33886 (3317) Repeatability 12.8 (12.0) Completeness (%) 99.95 (99.97) Average I/sigma(I) 13.85 (1.41) Wilson's B-factor 53.78 R-merge 0.1353 (1.658) R-meas 0.1412 (1.732) R-pim 0.03956 (0.4966) CC1/2 0.999 (0.591) CC* 1 (0.862) Reflections used in refinement 33879 (3317) Reflections used for R-free 1279 (128) R-work 0.2171 (0.2721) R-free 0.2623 (0.3245) CC(work) 0.957 (0.764) CC(free) 0.991 (0.670) Number of atoms other than a hydrogen atom 5624 Macromolecules 5497 Ligands 25 Solvent 102 Protein residues 715 RMS(relation) (Å) 0.011 RMS(angles) (deg.) 1.36 Percentage of residues in preferred area according to Ramachandran map (%) 90.70 Percentage of residues in the feasible region according to the Ramachandran map (%) 7.58 Marginal residuals according to Ramachandran map (%) 1.72 Percentage of deviation of side chains from rotamers (%) 0.49 Overlap index 9.45 Average B-factor value (Å ² ) 64.71 Macromolecules 64.92 Ligands 60.38 Solvent 54.67

Statistical values for the highest resolution shell are shown in parentheses.

Epitope determination for mAb01-9933

The epitope for mAb01-9933, defined as FIX(a) residues characterized by the presence of a heavy atom (i.e., an atom other than a hydrogen atom) within 3.5 Å of the heavy atom in Fab, includes the following residues: L337, R338, T340 and K341 according to SEQ ID NO:1.

Paratope determination in mAb01-9933

Additionally, the paratope in mAb01-9933, defined as Fab residues characterized by the presence of a heavy atom (i.e., an atom other than a hydrogen atom) at a distance of 3.5 Å from the heavy atom in FIXa, includes residues (sequential numbering): D30, D31, W53, S102, S104, N107 in the heavy chain variable domain (SEQ ID NO:35) and residues: Y91 and S92 in the light chain variable domain (SEQ ID NO:39).

Residues in bold are located in CDR sequences as determined using the Kabat definition, while the remaining paratope residue D30 (in the heavy chain variable domain) is a framework residue.

Example 8a Crystallization and epitope/paratope mapping of anti-FIX(a) mAb01-9985

Crystallization

The Fab fragment corresponding to mAb01-9985 was mixed at a 1:1 molar ratio with human factor IXa without the Gla domain (wild type), with inhibited EGR-CK expressed in bacterial cells, lot no. hGDFIXAWTEGR_11 (purchased from Cambridge ProteinWorks). The complex was subjected to size exclusion chromatography on a HiLoad 16/60 Superdex 200 pg column (GE Healthcare) performed with a buffer containing 20 mM Hepes, pH 7.5, 140 mM NaCl, 1 mM CaCl ₂ . Fractions containing the Fab/FIXa complex were pooled and concentrated to 10.1 mg/ml. Crystals of the Fab/FIXa complex were grown using the crystal microtransfer screening technique described in D'Arcy et al. (2014) Acta Crystallographica Section F 70, 1117–1126, using vapor diffusion in a sessile drop at 18°C. The crystal used was grown using 200 nl of a protein solution containing 10.1 mg/ml complex in 20 mM Hepes, pH 7.4, 140 mM NaCl, 1 mM CaCl ₂ mixed with 100 nl of seed material and 300 nl of 2 M ammonium sulfate , 0.1 M Hepes, pH 7.5, as precipitant, and incubated over 80 μl of precipitant. Seed material was obtained from crystals of the Fab fragment corresponding to mAb01-9933, in complex with human factor IXa without the Gla domain (wild type), with inhibited EGR-CK.

Diffraction Data Collection

The crystal was cryoprotected by adding 1.5 μL of precipitant with 20% ethylene glycol to the crystallization drop before flash cooling in liquid nitrogen. Diffraction data were collected at 100 K in the X10SA synchrotron radiation beam from Swiss Light Source (wavelength 1.00 Å) using a Pilatus3 6M pixel detector from Dectris. Auto-indexing, data integration and scaling were performed using programs from the XDS package (diffraction data statistics are summarized in Table 7a).

Defining and clarifying the structure

The asymmetric unit contains one Fab:FIXa complex, based on Matthews coefficient analysis. The structure was determined by molecular replacement using Phaser implemented in the Phenix software package, using the structure of the predefined Fab:FIXa complex as a search model. The correct amino acid sequence was modeled using COOT, and then the structure was refined using refinement steps in Phenix and manual reconstruction in COOT. The statistical values of the refinements are given in Table 7a.

Table 7a. Statistical values of collected and refined data

Wavelength (Å) 1.00 Resolution range (Å) 48.51 - 3.105 (3.216 - 3.105) Space group P 4 ₁ 22 Unit cell (Å, deg.) 97.03 97.03 254.51 90 90 90 Total number of reflections 295893 (28675) Number of unique reflections 22811 (2201) Repeatability 13.0 (13.0) Completeness (%) 99.80 (99.19) Average I/sigma(I) 4.30 (0.95) Wilson's B factor (Å ² ) 50.79 R-merge 0.692 (2.568) R-meas 0.7205 (2.672) R-pim 0.1985 (0.7295) CC1/2 0.957 (0.476) CC* 0.989 (0.803) Reflections used in refinement 22786 (2193) Reflections used for R-free 548 (53) R-work 0.2240 (0.3283) R-free 0.2794 (0.3814) CC(work) 0.940 (0.725) CC(free) 0.928 (0.614) Number of atoms other than a hydrogen atom 5690 Macromolecules 5595 Ligands 95 Protein residues 726 RMS(relation) (Å) 0.012 RMS(angles) (deg.) 1.70 Percentage of residues in preferred area according to Ramachandran map (%) 97.21 Percentage of residues in the feasible region according to the Ramachandran map (%) 2.65 Marginal residuals according to Ramachandran map (%) 0.14 Percentage of deviation of side chains from rotamers (%) 0.16 Overlap Index 3.58 Average B-factor value (Å ² ) 43.84 Macromolecules 43.53 Ligands 61.76

Statistical values for the highest resolution shell are shown in parentheses.

Epitope determination for mAb01-9985

The epitope for mAb01-9985, defined as FIX(a) residues characterized by the presence of a heavy atom (i.e., an atom other than a hydrogen atom) within 3.5 Å of the heavy atom in Fab, includes the following residues: L337, R338, S339, T340 and K341 according to SEQ ID NO:1.

Paratope determination in mAb01-9985

The paratope in mAb01-9985, defined as Fab residues characterized by the presence of a heavy atom (i.e., an atom other than a hydrogen atom) at a distance of 3.5 Å from the heavy atom in FIXa, contains residues (sequential numbering): H30, D31, W53, S102, S104, Y106 and N107 in the heavy chain variable domain (SEQ ID NO:51) and residues Y91 and S92 in the light chain variable domain (SEQ ID NO:55). Residues in bold are located in CDR sequences as determined using the Kabat definition, while the remaining paratope residue H30 (in the heavy chain variable domain) is a framework residue.

Example 9: Crystallization and epitope/paratope mapping of anti-FX antibodies using X-ray crystallography

Crystallization and epitope/paratope mapping of anti-FXa antibody mAb01-8174

Crystallization

The Fab fragment corresponding to mAb01-8174 was mixed at a 1:1 molar ratio with human factor Xa without the Gla domain (wild type), with inhibited EGR-CK expressed in bacterial cells, lot no. hGDFXAEGR_026 (purchased from Cambridge ProteinWorks), and Crystals of the Fab/FXa complex were grown using the sessile drop vapor diffusion technique at 18°C. 150 nl of a protein solution containing 4.7 mg/ml of the complex in 20 mM Tris-HCl, pH 7.4, 50 mM NaCl and 2.5 mM CaCl ₂ was mixed with 50 nl of 0.2 M sodium acetate, 0.1 M sodium cacodylate, pH 6.5, 18% (w/v) PEG 8000 as precipitant, and incubated over 60 μl of precipitant.

Diffraction Data Collection

The crystal was cryoprotected by adding 1 μL of precipitant with 20% ethylene glycol to the crystallization drop before flash cooling in liquid nitrogen. Diffraction data were collected at 100 K in the X06DA synchrotron radiation beam from Swiss Light Source (wavelength 1.00 Å) using a Pilatus2M pixel detector from Dectris. Auto-indexing, data integration and scaling were performed using programs from the XDS package (statistical values of the diffraction data are summarized in Table 8).

Defining and clarifying the structure

The asymmetric unit contains two Fab:FXa complexes based on Matthews coefficient analysis. The structure was determined by molecular replacement using Molrep implemented in the CCP4 software package, using the structures of predefined Fab:FXa complexes as search models. The correct amino acid sequence for Fab was modeled using COOT, and then the structure was refined using refinement steps in Phenix and manual reconstruction in COOT. The statistical values of the refinements are given in Table 8.

Table 8. Statistical values of collected and refined data

Wavelength (Å) 1,000 Resolution range (Å) 44.12 - 2.6 (2.693 - 2.6) Space group P2 ₁ Unit cell (Å, deg.) 63.13 105.25 145.78 90 89.995 90 Total number of reflections 302807 (30703) Number of unique reflections 58767 (5896) Repeatability 5.2 (5.2) Completeness (%) 99.90 (99.97) Average I/sigma(I) 12.31 (1.56) Wilson's B factor (Å ² ) 50.13 R-merge 0.1209 (1.024) R-meas 0.1346 (1.138) R-pim 0.05869 (0.4933) CC1/2 0.996 (0.523) CC* 0.999 (0.829) Reflections used in refinement 58761 (5896) Reflections used for R-free 1999 (202) R-work 0.2033 (0.3027) R-free 0.2623 (0.3140) CC(work) 0.857 (0.463) CC(free) 0.788 (0.347) Number of atoms other than a hydrogen atom 11641 Macromolecules 11145 Ligands 52 Solvent 444 Protein residues 1447 RMS(communications) 0.011 RMS(angles) 1.70 Percentage of residues in preferred area according to Ramachandran map (%) 95.74 Percentage of residues in the feasible region according to the Ramachandran map (%) 3.70 Marginal residuals according to Ramachandran map (%) 0.56 Percentage of deviation of side chains from rotamers (%) 0.32 Overlap index 22.55 Average B-factor 46.64 Macromolecules 46.94 Ligands 46.66 Solvent 39.14 Clarification of doubles h,-k,-l

Statistical values for the highest resolution shell are shown in parentheses.

Epitope determination for mAb01-8174

The epitope for mAb01-8174, defined as FXa residues characterized by the presence of a heavy atom (i.e., an atom other than a hydrogen atom) within 3.5 Å of the heavy atom in Fab in one or both complexes in an asymmetric unit, includes the following residues : E103, Q104, V108, R113, T116, L117, D119, I125, T127, E228, F229, Y230, E266, R287, P291, I292, P304, L419, K420, D423, R424, M426, K427 and T428 according to the SEQ according ID NO:2.

Paratope determination in mAb01-8174

The paratope in mAb01-8174, defined as Fab residues characterized by the presence of a heavy atom (i.e., an atom other than a hydrogen atom) within 3.5 Å of the heavy atom in FXa in one or both complexes in an asymmetric unit, includes residues ( sequential numbering): K23, S25, G26, Y27, F29, W33, D52, S54, D55, F57, S77, H100, Y101, Y102, N103, S104 in the heavy chain variable domain (SEQ ID NO:467) and residues V29 , S30, S31, Y33, Y50, Q52, S54, R55, R57 and D94 in the light chain variable domain (SEQ ID NO:471).

Residues in bold are located in CDR sequences as determined using the Kabat definition, while the remaining paratope residues K23, S25, G26, Y27, F29 and S77 (in the heavy chain variable domain) and Y50 (in the variable domain light chain) are framework residues.

Crystallization and epitope/paratope mapping of anti-FXa antibody mAb01-9772

The Fab fragment corresponding to mAb01-9772 was mixed at a 1:1 molar ratio with human factor Xa without the Gla domain (wild type), with inhibited EGR-CK expressed in bacterial cells, lot no. hGDFXAEGR_026 (purchased from Cambridge ProteinWorks), and Crystals of the Fab/FXa complex were grown using the sessile drop vapor diffusion technique at 18°C. 150 nl of a protein solution containing 3.7 mg/ml of the complex in 20 mM Tris-HCl, pH 7.4, 50 mM NaCl and 2.5 mM CaCl ₂ was mixed with 50 nl of 0.2 M sodium formate, 20% ( w/v) PEG 3350 as precipitant and incubated over 60 μl of precipitant.

Diffraction Data Collection

The crystal was cryoprotected by adding 1 μL of precipitant with 20% ethylene glycol to the crystallization drop before flash cooling in liquid nitrogen. Diffraction data were collected at 100 K in the X06DA synchrotron radiation beam from Swiss Light Source (wavelength 1.00 Å) using a Pilatus2M pixel detector from Dectris. Auto-indexing, data integration and scaling were performed using programs from the XDS package (statistical values of the diffraction data are summarized in Table 9).

Defining and clarifying the structure

The asymmetric unit contains two Fab:FXa complexes based on Matthews coefficient analysis. The structure was determined by molecular replacement using Molrep implemented in the CCP4 software package, using the structures of predefined Fab:FXa complexes as search models. The correct amino acid sequence for Fab was modeled using COOT, and then the structure was refined using refinement steps in Phenix and manual reconstruction in COOT. The statistical values of the refinements are given in Table 9.

Table 9: Statistical values of collected and refined data

Wavelength (Å) 1,000 Resolution range 48.33 - 3.15 (3.263 - 3.15) Space group P 2 ₁ Unit cell (Å, deg.) 62.34 104.72 144.98 90 90.048 90 Total number of reflections 102910 (10275) Number of unique reflections 31847 (3182) Repeatability 3.2 (3.2) Completeness (%) 98.16 (98.45) Average I/sigma(I) 8.51 (1.45) Wilson's B factor (Å ² ) 74.36 R-merge 0.126 (0.7224) R-meas 0.1512 (0.8628) R-pim 0.08262 (0.4665) CC1/2 0.994 (0.571) CC* 0.998 (0.853) Reflections used in refinement 31824 (3182) Reflections used for R-free 1083 (113) R-work 0.2163 (0.2810) R-free 0.2929 (0.2997) CC(work) 0.849 (0.374) CC(free) 0.736 (0.325) Number of atoms other than a hydrogen atom 11190 Macromolecules 11138 Ligands 52 Protein residues 1446 RMS(communications) 0.013 RMS(angles) 1.98 Percentage of residues in preferred area according to Ramachandran map (%) 95.03 Percentage of residues in the feasible region according to the Ramachandran map (%) 4.20 Marginal residuals according to Ramachandran map (%) 0.77 Percentage of deviation of side chains from rotamers (%) 0.00 Overlap index 26.08 Average B-factor value (Å ² ) 73.74 Macromolecules 73.78 Ligands 65.77 Clarification of doubles h,-k,-l

Statistical values for the highest resolution shell are shown in parentheses.

Epitope determination for mAb01-9772

The epitope for mAb01-9772, defined as FXa residues characterized by the presence of a heavy atom (i.e., an atom other than a hydrogen atom) within 3.5 Å of the heavy atom in Fab in one or both complexes in an asymmetric unit, includes the following residues : E103, Q104, V108, R113, T116, L117, A118, D119, I125, T127, S227, E228, Y230, R287, I292, L303, P30, L419, K420, D423, R424, M426, K427 and T428 according to the SeQ ID NO:2.

Paratope determination in mAb01-9772

The paratope in mAb01-9772, defined as Fab residues characterized by the presence of a heavy atom (i.e., an atom other than a hydrogen atom) within 3.5 Å of the heavy atom in FXa in one or both complexes in an asymmetric unit, includes residues ( sequential numbering): K23, G24, S25, G26, Y27, W33, D52, S54, D55, Y57, S77, L99, H100, Y101, Y102, N103 and S104 in the heavy chain variable domain (SEQ ID NO:483) and residues S30, S31, Y33, Y50, Q52, S54, R55, R57, Y92 and D94 in the light chain variable domain (SEQ ID NO:487).

Residues in bold are located in the CDR sequences as determined using the Kabat definition, while the remaining paratope residues K23, G24, S25, G26,Y27 and S77 (in the heavy chain variable domain) and Y50 (in the variable domain light chain) are framework residues.

Example 10. Identification of hot spot residues on FIX

To identify residues critical for the interaction (referred to as the “hot spot”) between the FIX/FIXa antibodies mAb01-9994 and mAb01-9985 and FIX, a set of FIX variants was selected based on the Fab/FIXa structure for the Fab fragment of mAb01-9994 and FIXa. As detailed below, selected FIX variants were transiently expressed in mammalian cells, purified, and characterized for their binding to monovalent variants mAb01-9994 and mAb01-9985 using surface plasmon resonance (SPR).

Generation of FIX mutants

A DNA plasmid suitable for transient expression in mammalian cells was constructed using an expression cassette encoding amino acid residues 1–461 of human FIX (UNIPROT P00740, excluding the T194A mutation according to UNIPROT numbering corresponding to T148A of SEQ ID NO:1), followed by immediately followed by six histidine residues (6×His tag intended for affinity purification). The secreted mature FIX protein chain produced using this construct is identical to the A148 allelic form of human FIX (Anson et al. EMBO J. 1984 3:1053–1060, McGraw et al., Proc Natl Acad Sci USA. 1985 82:2847–2851 ), except for the addition of a C-terminal His tag.

Using the construct as a template, selected mutations were introduced by PCR. For each point mutation listed in Table 10, a forward primer containing the required amino acid substitution and a reverse primer without amino acid mutations were designed. These primers were used in a standard PCR reaction with the vector described above as a template to amplify the complete vector sequence. Ligation-free cloning was used to join the ends of the resulting amplified DNA fragment into a circular expression plasmid using overlapping sequences introduced by forward and reverse primers.

The circular plasmids were transformed into E. coli cells, which were grown on selective agar plates to form colonies, and these colonies were used as inoculum for culturing E. coli in liquid nutrient medium. After E. coli cultures grew overnight, plasmid preparations were prepared and mutants were identified by DNA sequencing.

Recombinant protein production was accomplished by transfecting expi293F cells grown in suspension culture in Expi293 Expression™ medium (ThermoFisher Scientific, catalog no. A1435101), using the ExpiFectamine™ 293 transfection kit (ThermoFisher Scientific, catalog no. A14525) and plasmid DNA encoding each of the required FIX variants, as well as wild-type FIX (corresponding to SEQ ID NO:1 with a C-terminal His tag). Vitamin K was added at the time of transfection to a final concentration of 5 mg/ml. Transfection enhancers 1 and 2 from the ExpiFectamine™ 293 transfection kit were added the day after transfection. Cell cultures were harvested 5 days after transfection by centrifugation.

The C-terminal His tag in each FIX variant was used to purify a batch of protein in a multiwell robotic setup. Briefly, collected cell culture supernatants were adjusted for binding conditions, mixed with Ni Sepharose 6 Fast Flow affinity purification resin (GE Healthcare, part number 17-5318-02, 50 μl resin pelleted/ml cell culture medium) and incubated with shaking within 20 minutes. The resin/supernatant mixtures were then transferred to a filter plate and the liquid was pumped through the filter plate using a vacuum. The resin remaining on the filter plate was washed three times before eluting in high imidazole buffer.

Determination of the concentration of purified protein solutions was performed by ELISA using anti-FIX antibody for detection and high-purity recombinant wild-type FIX to generate standard curves.

The FIX variants were characterized by their binding to mAb01-9994 and mAb01-9985 using surface plasmon resonance (SPR) capturing the FIX variant via a C-terminal His tag. To avoid avidity effects, i.e. to ensure a 1:1 interaction, the single-arm (OA) variants mAb01-9994 and mAb01-9985 (prepared as described in Example 5) were used as analytes.

SPR analyzes were performed on Biacore T200 instruments (Biacore AB, Uppsala, Sweden). For experiments on the T200 device, the following conditions were used: measurements were carried out at a temperature of 25°C. Anti-His antibody at 25 μg/mL (R&D Systems, catalog number MAB050) was immobilized onto the CM5 sensor chip using standard amino immobilization chemistries. Anti-FIX antibody variants at 25 nM were injected at a flow rate of 10 μl/min for 1 min, and they were captured through their His tag by the immobilized anti-His antibody. Subsequently, 20 μM (2.5-fold dilution) of OA mAb01-9994 and OA mAb01-9985 were injected at a flow rate of 50 μl/min for 3 minutes to ensure binding to the captured FIX variant, followed by a 3-minute injection of buffer for ensuring the possibility of dissociation of monovalent antibodies to FIX. The working buffer was 20 mM Tris, 150 mM NaCl, 5 mM _CaCl2 , 0.05% Tween-20, 10 mg/ml BSA, pH 7.4. It was also used to dilute FIX antibody samples and FIX samples. Chip regeneration was carried out using 10 mM glycine, pH 2.0. Binding data were analyzed according to a 1:1 model using BiaEvaluation 4.1 provided by the manufacturer (Biacore AB, Uppsala, Sweden).

Binding data are presented as % antibody binding to the FIX variant relative to antibody binding to wild-type FIX, calculated using the formula:

Binding (%) = 100% × [(R _{max_Ab,FIX_var} )/(R _{max_FIXvar} )]/[(R _{max_Ab,FIX_wt} )/(R _{max_FIXwt} )]

where R _{max_FIXvar} and R _{max_FIXwt} represent the capture level (RU) of the FIX variant and wild-type FIX, respectively, and where R _{max_Ab,FIX_var} and R _{max_Ab,FIX_wt} represent the Rmax (RU) of 20 μM antibody with the captured FIX variant and wild-type FIX, respectively. The results are shown in Tables 10 and 11.

Table 10. SPR Assay Results (mAb01-9994)

Results of hot spot analysis for OA variant mAb01-9994

Remaining number Option FIX Binding (%) 301 K301A 89 332 D332S 41 332 D332A 41 333 R333A 55 334 A334L 38 335 T335A 43 337 L337A 38 338 R338A 0 339 S339L 46 340 T340A 16 341 K341E 3 341 K341A 18 343 T343I 62 343 T343A 58 346 N346Q 101 346 N346A 92 N.A. W.T. 100

Table 11. SPR Assay Results (mAb01-9985)

Results of hot spot analysis for OA variant mAb01-9985

Remaining number Option FIX Binding (%) 301 K301A 94 332 D332S 59 332 D332A 59 333 R333A 73 334 A334L 60 335 T335A 64 337 L337A 61 338 R338A 8 339 S339L 66 340 T340A 29 341 K341E 10 341 K341A thirty 343 T343I 84 343 T343A 86 346 N346Q 93 346 N346A 100 N.A. W.T. 100

Hotspot residues for mAb01-9994 and mAb01-9985
Hot spot residues for mAb01-9994 and mAb01-9985 are defined as positions at which replacement of the wild-type residue with alanine reduces antibody binding to 30% or less relative to antibody binding to wild-type FIX.

Hot spot residues for mAb01-9994:

R338, T340 and K341.

Hot spot residues for mAb01-9985:

R338, T340 and K341.

For both mAb01-9994 and mAb01-9985, the residue contributing the most to binding is R338; replacing R338 with alanine (R338A) in FIX showed the greatest effect on antibody binding, which was significantly reduced to no observed binding and 8% in the case of mAb01-9994 and mAb01-9985, respectively, relative to antibody binding to wild-type FIX.

Example 11: Identification of Hot Spot Residues on FX

The data presented in this example identifies epitope hotspot residues on FX for mAb01-8174. The FX variants used were desGla-desEGF1-FX variants with alanine at one site (except at position 118, which is alanine in the wild type protein, where an alanine to serine substitution was introduced), corresponding to residues 86-448 of SEQ ID NO:2 with an N-terminal His tag (HHHHHH) (SEQ ID NO:1200), for affinity purification) attached via a short GS linker (GGGGSGGGGS) (SEQ ID NO:1201). The FX options tested are listed in Table 12.

Table 12. List of obtained desGla-desEGF1-FX mutants

Position ¹⁾ Option Domain ²⁾ 101 H101A EGF2 103 E103A EGF2 113 R113A EGF2 116 T116A EGF2 118 A118S EGF2 127 T127A EGF2 227 S227A P.D. 228 E228A P.D. 229 F229A P.D. 230 Y230A P.D. 266 E266A P.D. 287 R287A P.D. 305 E305A P.D. 419 L419A P.D. 420 K420A P.D. 423 D423A P.D. 424 R424A P.D. 427 K427A P.D. 428 T428A P.D.

1. According to SEQ ID NO:2

2. EGF2 and PD belong to the second epidermal growth factor-like domain and protease domain, respectively.

Wild type DesGla-desEGF1-FX and the variants listed in Table 12 were expressed in the HEK293 system and purified by affinity chromatography. Identification of epitope hot spot residues was performed using a Biacore 4000 instrument at 25°C. Wild-type DesGla-desEGF1-FX and its variants were immobilized on a CM5 Series-S sensor chip (GE Healthcare, cat. no. BR100530) using standard amine immobilization chemistries. 10 μM (2-fold serial dilutions) of the single-arm variant mAb01-8174 was injected at a flow rate of 10 μl/min for 300 s to allow binding to the immobilized wild-type desGla-desEGF1-FX and its variants, followed by a 600 s injection buffer to allow dissociation of the monovalent antibody. The running buffer (also used to dilute the monovalent antibody and desGLA-desEGF1-hFX variants) contained 10 mM HEPES, 150 mM NaCl, 1 mg/ml BSA and 5 mM CaCl ₂ (pH 7.4). No regeneration buffer was used because almost complete dissociation of the antibody from the sensor chip was observed during the 600 second dissociation step. Binding data were analyzed according to a 1:1 model and the affinity (i.e., equilibrium dissociation constant) for each binding was obtained by fitting the steady state binding curves using Biacore 4000 Evaluation 1.0 software provided by GE Healthcare. Binding data are presented as a multiple of the affinity of all FX variants for the antibody relative to the affinity of wild-type FX. The relative affinities measured for the FX variants are shown in Table 13.

Table 13. Relative affinity values (K _D (variant)/K _D (wild type)) for binding of single-arm mAb01-8174 to FX variants

Option Relative affinity value Wild type 1.0 H101A 3.6 E103A 3.5 R113A 2.3 T116A 0.55 A118S 1.5 T127A 0.85 S227A 2.8 E228A 0.85 F229A 0.95 Y230A No binding E266A 0.65 R287A > 5 E305A 2.1 L419A 4.5 K420A > 5 D423A No binding R424A No binding K427A No binding T428A 1.0

“No binding” means that the binding was too weak to be detected.

Hot spot residues for mAb01-8174
As shown in Table 13, alanine substitutions at positions 230, 423, 424 and 427 in FX completely abolished binding to single-arm mAb01-8174. Thus, the hotspot residues on FX for binding to mAb01-8174 are:

Y230, D423, R424 and K427.

Example 12. Activity of monovalent antibodies to FIX/FIXa in the FXa production assay

To avoid any potential avidity effects arising from the bivalence of the traditional IgG antibody format, the stimulatory activity of anti-FIX(a) antibodies on the FX enzymatic activity of FIXa was determined after conversion to a monovalent single-arm (OA) antibody format (see Example 5). The antibodies tested are listed in Table 14 below. Monovalent OA versions of FIXa antibodies, 224F3 and ACE910, were included for comparison.

OA antibody stimulatory activity was measured in assay buffer (50 mM HEPES, 100 mM NaCl, 5 mM CaCl ₂ , 0.1% (w/v) PEG8000, pH 7.3, +1 mg/mL BSA) at fixed concentrations phospholipid vesicles from phosphatidylserine (PS): phosphatidylcholine (PC) (final concentration 500 μM; Haematologic Technologies Inc, USA) and plasma-derived FIXa (final concentrations 0.04, 0.1, 0.17, 0.2, 0 .3, 0.5 or 1 nM; Haematologic Technologies Inc, USA). The concentration of FIXa was adjusted to ensure that less than 15% of the FX substrate was converted to FXa. After preincubation in the presence of monovalent OA antibody (final concentrations are listed in Table 14), 100 nM plasma-derived FX (Haematologic Technologies Inc, USA) was added to obtain a final reaction volume of 50 μl and activation was allowed to proceed for 20 min at room temperature. temperature. The reaction was then stopped by adding 25 μl of stop buffer (50 mM HEPES, 100 mM NaCl, 60 mM EDTA, 0.1% PEG8000, pH 7.3, +1 mg/ml BSA) and the amount of FXa produced was determined using further adding 25 μl of 2 mM chromogenic substrate S-2765 (Chromogenix, Sweden) and measuring the conversion of the chromogenic substrate by measuring absorbance at 405 nm (ΔOD/min) in a microplate reader. The measured activity was corrected for background activity by subtracting the signal measured in the same assay but replacing FIXa and antibody with assay buffer, and then normalized according to the concentration of FIXa present in the assay ([FIXa] _total ). By dividing this number by the similarly normalized rate of FXa production in the absence of the antibody (A _FIXa,norm ), the antibody stimulation index was calculated, showing the multiple stimulation of FIXa activity by the antibody at the concentration used. Due to the low rate of FXa formation by free FIXa, activation reactions in the absence of antibody were performed as described above, but in the presence of 5, 10, or 20 nM FIXa. The measured activity values were then background subtracted and normalized according to the concentration of FIXa in the assay. The average of three normalized free FIXa activity values was used to calculate the stimulation index.

Determination of the stimulation index

Thus, the calculation of the stimulation index can be described as follows.

Stimulation index = ((A _FIXa+OA – A _background )/[FIXa] _general )/A _FIXa,norm ,

where A _FIXa+OA is the activity measured in the presence of OA antibody, A _background is background activity measured in the absence of FIXa and OA antibody, [FIXa] _total is the concentration of FIXa in the assay, and A _FIXa,norm is mean normalized free FIXa activity.

Determination of saturation FIXa

The proportion of FIXa saturated with OA antibody in the assay is determined from the concentrations of FIXa and OA antibody and the equilibrium dissociation constant (K _d ) governing their interaction. The latter can be measured using techniques known in the art, such as isothermal titration calorimetry (ITC).

Because the stimulation index will increase as the OA antibody concentration increases until FIXa saturation is achieved, the concentration of the OA antibody in the assay should be selected to ensure at least 80% FIXa saturation in the assay to ensure proper determination of the stimulation index at full saturation FIXa.

The fraction of FIXa bound to OA antibody at steady state (f _FIXa+OA ) can be calculated from the total concentrations of FIXa ([FIXa] _total ) and OA antibody ([OA] _total ) in the assay and the equilibrium dissociation constant ( _Kd ) for their interaction using the quadratic coupling equation described in Krishnaswamy et al. (1992) J. Biol. Chem., 267:23696–23706 and detailed in Equations 1 and 2 below, where

represents the calculated concentration of the FIXa-OA-antibody complex at steady state in the assay;

represents the calculated fraction (percentage) of FIXa that is bound to OA antibody at steady state in the assay.

Equation 1:

Equation 2:

The stimulation index for each OA antibody is shown in Table 14. With the concentration of OA antibody 224F3 being 3260 nM in the assay and the K _d for interaction with FIXa being 0.477 nM as reported by Kerschbaumer et al. (US7297336B2), more than 95% of FIXa bound to the OA antibody 224F3 in the assay. For the OA antibody ACE910, FIXa stimulation was determined at eight different antibody concentrations, allowing the stimulation index to be estimated at full FIXa saturation using the quadratic binding equation described above. This also gave a calculated equilibrium dissociation constant (K _d ) for the interaction of ACE910 with FIXa of 1.1 μM, which is in good agreement with the value of 1.52 μM reported in Kitazawa et al. (2017) Thromb Haemost, 117:1348–1357, and the value of 1.97 μM determined using ITC in example 13. For the remaining antibodies, the degree of saturation of FIXa was not known, and therefore the stimulation indices listed represent preliminary estimates of stimulation, which can be obtained with a degree of FIXa saturation of 80% or more. For the antibodies tested, the stimulation index measured was found to be higher than the stimulation index measured for the OA antibodies 224F3 and ACE910.

Table 14. Stimulation of FIXa activity by monovalent single-arm (OA) antibodies to FIXa

The FIX mAb ID refers to the ID of the antibody used for conversion to OA format. The columns labeled “OA Antibody Concentration (nM)” and “Stimulation Index” list the OA Antibody Concentration (nM) used in the assay and the corresponding stimulation of FIXa activity measured relative to free FIXa. For ACE910, the calculated stimulation index at full FIXa saturation is shown.

ID mAb to FIX OA antibody concentration (nM) Stimulation index ACE910 saturation 1372 224F3 3260 <10 01-9016 1600 5905 01-9373 1600 1392 01-9696 1600 5166 01-9697 3200 6539 01-9933 3600 6444 01-9978 3600 3667 01-9985 2400 13730 01-9986 800 5822 01-9994 3600 10593 11-0047 800 2856 11-0049 800 1509 11-0107 800 3264 11-0149 800 3315 11-0160 800 4549 11-0164 800 3269 11-0173 1600 8480 11-0174 800 3690 11-0723 800 3772 11-0923 800 2823 11-0929 800 1559 11-0931 800 1882 11-0932 800 1688 11-0933 800 1614 11-0935 800 1572 11-0937 800 2684 11-0938 800 1818 11-0939 800 2011 11-0962 800 3372 11-0965 800 2857 11-1021 800 4646 11-1024 800 3654 11-1030 800 5751 11-1033 800 5126 11-1039 800 3960 11-1042 800 4316 11-1073 800 6146 11-1076 800 3587 11-1091 800 5402 11-1094 800 4083 11-1204 1600 9099 11-1233 800 1700 11-1254 760 1890 11-1259 800 2005 11-1260 800 1757 11-1262 800 1952 11-1266 800 1696 11-1268 800 1796 11-1273 800 1540 11-1275 800 1835 11-1276 800 1739 11-1278 800 1694 11-1279 800 1562 11-1282 800 1461 11-1286 800 1816 11-1288 800 2534 11-1344 800 4662 11-1358 800 2831 11-1360 800 1114 11-1389 800 5786 11-1495 1600 7694 11-1499 1600 9013 11-1501 1600 10277 11-1502 1600 5853

Example 13 Binding Affinities Determined by Isothermal Titration Calorimetry (ITC)

Binding affinities for anti-FIX(a) and anti-FX(a) antibodies were measured by isothermal titration calorimetry (ITC) using a PEAQ-ITC calorimeter (Malvern, UK). Experiments were performed at 37°C and pH 7.4 using 25 mM Tris, 150 mM NaCl, 5 mM CaCl ₂ (Tris buffer). The sample well (200 μl) contained one of FIX, FIXa or FX (macromolecule), and anti-FIX(a) and anti-FX(a) (ligand) antibodies were injected through a syringe (40 μl). All proteins were dialyzed extensively in Tris buffer prior to measurements to maintain suitable buffer conditions. The thermal equilibration step was followed by a 60-second delay and then an initial injection of 0.2 μl of antibody followed by 12-16 injections of 1.5-3 μl of antibody at 120-s intervals. The stirring speed was maintained at 750 rpm and the initial power level was kept constant at 5–10 μcal/s. The heat associated with each antibody injection is integrated and plotted against the molar ratio of ligand to macromolecule. The resulting isotherm is fitted to a single site binding model to obtain affinity (K _D ), stoichiometry (n) and enthalpy of interaction (ΔH) using software provided by the manufacturer. Experiments were performed at least in duplicate. K _D values in µM units are presented in Table 15.

Table 15. Dissociation constant ( _KD ) values using ITC

_KD , µM FIX FIXa FX mAb01-9994 2.48 ± 0.23 1.8 ± 0.13 N.A. mAb01-9933 2.39 ± 0.33 1.3 ± 0.12 N.A. mAb01-9985 1.92 ± 0.18 1.26 ± 0.08 N.A. mAb01-9978 5.6 ± 0.93 3.57 ± 0.52 N.A. mAb01-8913 N.A. N.A. 0.35 ± 0.19 mAb01-8174 N.A. N.A. 0.75 ± 0.66 mAb01-9772 N.A. N.A. 1.37 ± 0.39 ACE910 2.77 ± 1.44 1.97 ± 0.42 2.42 ± 0.2

NA: Not applicable because the antibody is specific for another macromolecule.

Example 14. Activity of bispecific antibodies to FIX(a)/FX(a) in the FXa production assay

The procoagulant activity of FIXa/FX bispecific antibodies was determined based on their ability to stimulate FX activation by FIXa in the presence of a procoagulant phospholipid membrane. The bispecific antibodies (BiAbs) tested are listed in Table 16, and ACE910 is included for comparison.

The procoagulant activity of each bispecific antibody is described as the fold stimulation compared to FX activation by free FIXa at a given antibody concentration. Bispecific antibodies were tested at 8 concentrations (prepared by serial threefold dilutions in assay buffer) by preincubation with 35 or 125 pM FIXa derived from human plasma (Haematologic Technologies Inc., USA) and 500 µM phospholipid vesicles from 25:75 phosphatidylserine:phosphatidylcholine (Haematologic Technologies Inc, USA) in assay buffer (50 mM HEPES, 100 mM NaCl, 5 mM CaCl ₂ , 0.1% (w/v) PEG8000, pH 7.3, +1 mg/ml BSA ) for 10 minutes. Activation was then initiated by adding FX derived from human plasma (Haematologic Technologies Inc, USA) to a concentration of 25 nM. After 15 minutes of activation at room temperature, the reaction (50 μl) was stopped by adding 25 μl of stopping buffer (50 mM HEPES, 100 mM NaCl, 60 mM EDTA, 0.1% PEG8000, pH 7.3, +1 mg/ ml BSA). The amount of FXa produced was determined by adding 25 μL of 2 mM chromogenic substrate S-2765 (Chromogenix, Sweden) and measuring the conversion of the chromogenic substrate by measuring absorbance at 405 nm (ΔOD/min) in a microplate reader. Similarly, activation of FX by free FIXa was determined at a FIXa concentration of 25 nM and a reaction time of 60 min.

The measured activity was normalized according to the concentration of FIXa present in the assay and the reaction time. By dividing this number by the similarly normalized rate of FXa production in the absence of antibody, the fold stimulation by antibody at a given concentration was calculated.

Thus, the biAb stimulation calculation can be described as follows:

Stimulation biAb = (A _FIXa+biAb /([FIXa] _analysis × t _reaction ))/A _FIXa,norm ,

where A _FIXa+biAb represents the activity measured in the presence of the bispecific antibody, [FIXa] _assay represents the concentration of FIXa in the assay, t _reaction represents the reaction time, and A _FIXa,norm represents the normalized activity of free FIXa.

Table 16 lists the maximum stimulation determined for each bispecific antibody among the 8 antibody concentrations tested, as well as the concentration at which maximum stimulation was observed. For all bispecific antibodies tested, the maximum stimulation was found to be greater than that measured for ACE910, which was tested over a concentration range from 0 to 15,300 nM.

Table 16: Maximum stimulation with bispecific antibodies to FIXa/FX

Antibody ID biAb Test Concentration Range (nM) Conc. biAb at maximum stimulation (nM) Maximum stimulation (multiplicity) ACE910 14.38-31440 10480 891 bimAb05-0745 3.65-7980 7980 21143 bimAb05-3761 3.69-8070 2690 16332 bimAb05-3769 3.735-8170 8170 27417 bimAb05-0746 5.1-11150 3717 14595 bimAb05-2112 3.575-7820 7820 30426 bimAb05-2113 3.475-7600 7600 26321 bimAb05-2114 3.465-7580 7580 35222 bimAb05-2115 3.56-7790 7790 14921 bimAb05-3755 1.93-4212 156 7573

Example 15. TGT for bispecific antibodies to FIX(a)/FX(a) in blood plasma in hemophilia A (HA)

Thrombin generation tests (TGT) were performed in an automated 384-well HTP machine with tissue factor stimulation. Briefly, 10 μl of antibody was added to 30 μl of hemophilia A (HA) blood plasma (George King). Next, 10 μl of TissueFactor stimulator (Thrombinoscope, no. TS31.00) mixed with phospholipids was added, followed by the addition of 10 μl of thrombin substrate (FluCa, Thrombinoscope, no. TS50.00) to a final assay volume of 60 μl. Fluorescence time series were measured at room temperature on an EnVision Perkin Elmer multilabel plate reader at 1-minute intervals for 2 hours. Thrombograms were calculated as the smoothed first derivative of fluorescence time series. Peak height was calculated as the maximum value observed in the thrombogram and normalized (peak ratio) to the peak height observed for the reference antibody ACE910 at the highest concentration (333 nM). The test results for bispecific antibodies (bimAb) are shown in Table 17. The peak ratio (fold) represents the maximum value observed for bimAb in the thrombogram compared to the value for ACE910 at 333 nM. The concentration (nM) at which the peak is observed is also indicated.

Table 17. TGT activity for bimAb to FIX/FX relative to ACE910

ID bimAb ID mAb to FIX ID mAb to FX Concentration (nM) Peak ratio (fold) bimAb05-0396 mAb11-1495 mAb01-8174 111 1.18 bimAb05-0417 mAb11-1501 mAb01-8174 111 1.25 bimAb05-0438 mAb11-1502 mAb01-8174 333 1.10 bimAb05-0745 mAb01-9994 mAb01-8174 111 1.24 bimAb05-2114 mAb01-9985 mAb01-9772 333 1.07 bimAb05-2375 mAb01-9016 mAb01-8174 111 1.14 bimAb05-2379 mAb01-9016 mAb01-8913 666 1.26 bimAb05-2532 mAb01-9373 mAb01-6723 333 1.24 bimAb05-3416 mAb01-9985 mAb01-6723 111 1.13 bimAb05-3769 mAb01-9985 mAb01-8174 111 1.27 bimAb05-3770 mAb01-9986 mAb01-8174 333 1.23 bimAb05-3862 mAb01-9696 mAb01-8174 333 1.52 bimAb05-3880 mAb11-0047 mAb01-8174 333 1.4 bimAb05-3886 mAb11-0049 mAb01-8174 333 1.16 bimAb05-3955 mAb11-0107 mAb01-8174 333 1.34 bimAb05-4100 mAb11-0149 mAb01-8174 333 1.25 bimAb05-4114 mAb11-0160 mAb01-8174 333 1.26 bimAb05-4121 mAb11-0164 mAb01-8174 333 1.34 bimAb05-4220 mAb11-0962 mAb01-8174 333 1.39 bimAb05-4226 mAb11-0965 mAb01-8174 333 1.31 bimAb05-4271 mAb11-0173 mAb01-8174 111 1.32 bimAb05-4283 mAb11-1021 mAb01-8174 333 1.19 bimAb05-4289 mAb11-1024 mAb01-8174 333 1.06 bimAb05-4292 mAb11-1033 mAb01-8174 111 1.19 bimAb05-4293 mAb11-1030 mAb01-8174 111 1.35 bimAb05-4387 mAb11-1039 mAb01-8174 333 1.28 bimAb05-4392 mAb11-1042 mAb01-8174 111 1.24 bimAb05-4419 mAb11-0174 mAb01-8174 111 1.21 bimAb05-4422 mAb11-1073 mAb01-8174 333 1.2 bimAb05-4428 mAb11-1076 mAb01-8174 111 1.12 bimAb05-4443 mAb11-1094 mAb01-8174 333 1.14 bimAb05-4444 mAb11-1091 mAb01-8174 333 1.19 bimAb05-4601 mAb11-0937 mAb01-8174 111 1.17 bimAb05-4604 mAb11-0923 mAb01-8174 333 1.02 bimAb05-4611 mAb11-0935 mAb01-8174 333 1.02 bimAb05-4612 mAb11-0938 mAb01-8174 111 1.23 bimAb05-4613 mAb11-0933 mAb01-8174 333 1.03 bimAb05-4684 mAb01-9985 mAb11-1114 333 1.05 bimAb05-4685 mAb01-9985 mAb11-1115 111 1.12 bimAb05-4686 mAb01-9985 mAb11-1116 333 1.16 bimAb05-4687 mAb01-9985 mAb11-1117 333 1.12 bimAb05-4688 mAb01-9985 mAb11-1118 111 1.16 bimAb05-4689 mAb01-9985 mAb11-1119 333 1.26 bimAb05-4690 mAb01-9985 mAb11-1121 333 1.36 bimAb05-4693 mAb01-9985 mAb11-1123 333 1.02 bimAb05-4696 mAb01-9985 mAb11-1125 333 1.3 bimAb05-4704 mAb01-9985 mAb11-1416 333 1.17 bimAb05-4708 mAb01-9985 mAb11-1420 111 1.02 bimAb05-4710 mAb01-9985 mAb11-1422 333 1.1 bimAb05-4756 mAb11-1204 mAb01-8174 111 1.20 bimAb05-4788 mAb11-1233 mAb01-8174 333 1.13 bimAb05-4884 mAb11-1254 mAb01-8174 316 1.16 bimAb05-4895 mAb11-1262 mAb01-8174 111 1.28 bimAb05-4896 mAb11-1259 mAb01-8174 333 1.13 bimAb05-4898 mAb11-1260 mAb01-8174 333 1.17 bimAb05-4903 mAb11-1268 mAb01-8174 333 1.1 bimAb05-4906 mAb11-1266 mAb01-8174 111 1.38 bimAb05-4910 mAb11-1273 mAb01-8174 333 1.12 bimAb05-4914 mAb11-1275 mAb01-8174 333 1.16 bimAb05-4915 mAb11-1276 mAb01-8174 111 1.23 bimAb05-4919 mAb11-1278 mAb01-8174 333 1.17 bimAb05-4920 mAb11-1282 mAb01-8174 111 1.22 bimAb05-4921 mAb11-1279 mAb01-8174 333 1.14 bimAb05-4924 mAb11-1288 mAb01-8174 333 1.22 bimAb05-4927 mAb11-1286 mAb01-8174 333 1.22 bimAb05-5092 mAb11-1344 mAb01-8174 111 1.23 bimAb05-5095 mAb11-0723 mAb01-8174 111 1.31 bimAb05-5204 mAb11-1358 mAb01-8174 333 1.5 bimAb05-5205 mAb11-1360 mAb01-8174 111 1.38 bimAb05-5240 mAb11-1389 mAb01-8174 111 1.29 bimAb05-5340 mAb01-9985 mAb11-1431 111 1.28 bimAb05-5341 mAb01-9985 mAb11-1441 111 1.05 bimAb05-5342 mAb01-9985 mAb11-1439 333 1.14 bimAb05-5344 mAb01-9985 mAb11-1443 333 1.03 bimAb05-5346 mAb01-9985 mAb11-1444 158 1.17 bimAb05-5348 mAb01-9985 mAb11-1445 111 1.19 bimAb05-5353 mAb01-9985 mAb11-1453 333 1.15 bimAb05-5354 mAb01-9985 mAb11-1451 116 1.01 bimAb05-5356 mAb01-9985 mAb11-1452 111 1.16 bimAb05-5357 mAb01-9985 mAb11-1455 333 1.11 bimAb05-5358 mAb01-9985 mAb11-1433 111 1.22 bimAb05-5359 mAb01-9985 mAb11-1456 333 1.07 bimAb05-5361 mAb01-9985 mAb11-1459 111 1.21 bimAb05-5362 mAb01-9985 mAb11-1457 111 1.39 bimAb05-5363 mAb01-9985 mAb11-1434 333 1.56 bimAb05-5364 mAb01-9985 mAb11-1458 111 1.18 bimAb05-5365 mAb01-9985 mAb11-1460 333 1.04 bimAb05-5366 mAb01-9985 mAb11-1461 333 1.12 bimAb05-5367 mAb01-9985 mAb11-1465 333 1.15 bimAb05-5369 mAb01-9985 mAb11-1466 333 1.17 bimAb05-5370 mAb01-9985 mAb11-1463 333 1.06 bimAb05-5371 mAb01-9985 mAb11-1435 208 1.19 bimAb05-5372 mAb01-9985 mAb11-1464 333 1.05 bimAb05-5373 mAb01-9985 mAb11-1467 333 1.15 bimAb05-5374 mAb01-9985 mAb11-1468 333 1.07 bimAb05-5375 mAb01-9985 mAb11-1472 308 1.27 bimAb05-5377 mAb01-9985 mAb11-1473 111 1.27 bimAb05-5378 mAb01-9985 mAb11-1470 333 1.16 bimAb05-5379 mAb01-9985 mAb11-1436 111 1.07 bimAb05-5380 mAb01-9985 mAb11-1471 333 1.09 bimAb05-5381 mAb01-9985 mAb11-1474 333 1.15 bimAb05-5383 mAb01-9985 mAb11-1477 111 1.05 bimAb05-5385 mAb01-9985 mAb11-1478 333 1.03 bimAb05-5386 mAb01-9985 mAb11-1476 333 1.08 bimAb05-5387 mAb01-9985 mAb11-1479 333 1.27 bimAb05-5388 mAb01-9985 mAb11-1480 111 1.36 bimAb05-5389 mAb01-9985 mAb11-1483 111 1.19 bimAb05-5390 mAb01-9985 mAb11-1437 133 1.06 bimAb05-5396 mAb01-9985 mAb11-1487 111 1.07 bimAb05-5406 mAb01-9985 mAb11-1494 333 1.19

Example 16. Activity of bispecific antibodies to FIX(a)/FX(a) in the thrombin generation test (TGT) in platelet-poor or platelet-rich plasma of a person with simulated hemophilia A

The procoagulant activity of bispecific antibodies bimAb05-0745, bimAb05-3761, bimAb05-3769, bimAb05-0746, bimAb05-2112, bimAb05-2113 and bimAb005-2114 was determined based on their ability to stimulate thrombin formation in the presence of either a procoagulant synthetic phospholipid membrane, or platelets in according to the principles described in Hemker et al. (Pathophysiol Haemost Thromb 2002;32:249–253). ACE910 was included for comparison. Each antibody (test compound) was tested in a thrombin generation test (TGT) using commercially available pooled hemophilia A (HA) platelet-poor plasma (HA-PPP) and HA-induced human platelet-rich plasma (HA-PRP) freshly prepared from the blood of healthy consenting donors.

Materials and methods

Preparation of platelet-rich plasma from a person with induced hemophilia A (HA-PRP)

Blood was obtained from healthy, consenting donors by venipuncture. Six volumes of blood were collected in 1 volume of acid citrate dextrose (ACD; 85 mM sodium citrate, 110 mM dextrose, and 62.3 mM citric acid, pH 4.9), final pH 6.5, and centrifuged for 20 min at 220 g at room temperature (RT). Platelet-rich plasma (PRP) was collected and platelet concentrations were determined using a Medonic CA 620 hematology analyzer (Boule Diagnostics AB, Sponga, Sweden).

The part of the blood plasma containing erythrocytes was centrifuged for another 10 min at 600 g at RT. Platelet-poor plasma (PPP) was collected and used to dilute PRP to ∼300,000 platelets/μL. HA conditions were induced by adding anti-human FVIII-neutralizing antibody (sheep anti-human factor VIII antibody - 5 mg, Haematologic Technologies, Vermont, USA) to a final concentration of 0.1 mg/ml and stirred gently at 2 rpm for 30 minutes at RT.

Thrombin formation test

Thrombin generation tests (TGT) in HA-PPP (George King Bio-Medical Inc, Kansas, USA) (experiment A) and HA-PRP (experiment B) were performed using standard-calibrated automated thrombography using a 96-well plate fluorimeter (Fluoroscan Ascent FL, Thermolabsystems, Helsinki, Finland). Reaction mixtures contained 70 μl HA-PRP (~300,000 platelets/μl) or HA-PPP, 10 μl test compound dilution (diluted in 20 mM HEPES, 140 mM NaCl, pH 7.4, 2% BSA), 20 μl CAT reagents containing tissue factor (TF) (PRP reagent; TF without synthetic phospholipids, PPP LOW reagent; TF with synthetic phospholipids, final concentration of TF 1 pM, Thrombinoscope BV, Maastricht, the Netherlands) or thrombin calibrator (Thrombinoscope BV) and 20 μl of the mixture, containing fluorescently labeled thrombin substrate z-Gly-Gly-Arg-AMC (3 mM) and CaCl ₂ (90 mM) (Thrombinoscope BV). TGT was performed at eight concentrations of test compound (0.3, 1.0, 3, 10, 30, 100, 300 and 900 nM final plasma concentration) or with the addition of buffer (20 mM HEPES, 140 mM NaCl, pH 7 ,4, 2% BSA) (represents HA control). Concentration ranges were tested in at least three independent experiments in HA-PPP from the same parent preparation or in blood from four different donors. Normal control TGT levels were measured using untreated human PRP or CRYOcheck™ pooled normal human PPP plasma (Precision Biologic Inc., Dartmouth, Canada) supplemented with buffer (20 mM HEPES, 140 mM NaCl, pH 7.4, 2% BSA) . TGT was performed for a total of 90 minutes and the TGT parameter of peak thrombin height (nM) was analyzed using Thrombinoscope software (Thrombinoscope BV).

Results and discussion

Experiment A: Figure 2 and Table 18 show the measured peak thrombin generation rates for each bispecific antibody at the concentrations tested in HA-PPP. The data show that all tested compounds increase peak thrombin generation above the level observed in the absence of antibody, i.e., exhibit procoagulant activity. In addition, the thrombin generation levels for bimAb05-0745, bimAb05-3761, bimAb05-3769, bimAb05-0746, bimAb05-2112, bimAb05-2113, and bimAb05-2114 at concentrations ranging from 10 to 300 nM were higher than the levels observed for ACE910. which demonstrates their superior activity. In addition, the thrombin generation levels for bimAb05-0745, bimAb05-3761, bimAb05-3769, bimAb05-2112, and bimAb05-2114 at concentrations at 300–900 nM were higher than the levels observed at 900 nM ACE910, demonstrating higher values activity and efficacy of these compounds compared to ACE910.

Experiment B Figure 3 and Table 19 show the measured peak thrombin generation levels for each bispecific antibody at the concentrations tested in HA-PRP. Under these conditions, bimAb05-0745, bimAb05-3761, bimAb05-3769, bimAb05-0746, bimAb05-2112, bimAb05-2113 and bimAb05-2114 also show better potency and potency values compared to ACE910.

Table 18. Thrombin Generation Test (TGT) in HA-PPP (Experiment A)

Thrombin generation test (TGT) for bispecific antibodies bimAb05-0745, bimAb05-3761, bimAb05-3769, bimAb05-0746, bimAb05-2112, bimAb05-2113, bimAb05-2114 and ACE910 in tissue factor-activated platelet-poor human plasma in hemo filia A ( PPP). Average peak levels of thrombin generation ± standard deviation measured at each concentration of test compound in HA-PPP in at least three independent experiments (experiment A).

Experiment A
Compound concentration (nM) Peak Thrombin Level
(mean ± SD in nM)
for ACE910 Peak Thrombin Level
(mean ± SD in nM)
for bimAb05-0745 Peak Thrombin Level
(mean ± SD in nM)
for bimAb05-3761 0 15.5 ± 7.8 11.6 ± 0.9 11.6 ± 0.9 0.3 11.5 ± 1.1 11.6 ± 1.9 11.4 ± 0.7 1 12.6 ± 0.1 11.8 ± 1.2 13.5 ± 1.6 3 11.2 ± 2.5 14.0 ± 3.6 13.8 ± 2.7 10 13.3 ± 0.0 25.5 ± 5.8 18.1 ± 3.8 thirty 15.3 ± 4.3 44.8 ± 5.8 35.7 ± 5.4 100 22.0 ± 4.1 81.4 ± 9.2 64.1 ± 9.2 300 31.6 ± 4.0 105.7 ± 7.7 85.7 ± 7.0 900 45.6 ± 7.2 107.7 ± 14.1 78.4 ± 7.5 Experiment A
Compound concentration (nM) Peak Thrombin Level
(mean ± SD in nM)
for bimAb05-3769 Peak Thrombin Level
(mean ± SD in nM)
for bimAb05-0746 Peak Thrombin Level
(mean ± SD in nM)/
for bimAb05-2112 0 11.6 ± 0.9 11.6 ± 0.9 11.6 ± 0.9 0.3 14.6 ± 3.8 11.1 ± 1.2 9.4 ± 2.5 1 12.3 ± 0.8 12.4 ± 2.5 11.8 ± 1.0 3 14.7 ± 3.2 13.1 ± 3.2 12.0 ±1.1 10 25.4 ± 4.8 12.6 ± 1.3 12.7 ± 1.2 thirty 50.8 ± 8.7 15.3 ± 0.9 17.0 ± 4.0 100 94.1 ± 7.5 29.0 ± 3.6 29.1 ± 5.7 300 117.5 ± 8.1 44.2 ± 5.2 51.2 ± 5.7 900 112.5 ± 11.0 47.8 ± 6.0 82.8 ± 7.5 Experiment A
Compound concentration (nM) Peak Thrombin Level
(mean ± SD in nM)
for bimAb05-2113 Peak Thrombin Level
(mean ± SD in nM)
for bimAb05-2114 0 11.6 ± 0.9 11.6 ± 0.9 0.3 14.2 ± 5.2 11.9 ± 0.5 1 11.5 ± 1.2 12.3 ± 0.8 3 11.8 ± 0.7 12.9 ± 1.2 10 13.0 ± 2.7 15.7 ± 2.8 thirty 15.7 ± 5.4 21.3 ± 5.1 100 22.4 ± 5.5 41.9 ± 14.5 300 40.7 ± 7.2 75.8 ± 17.0 900 51.1 ± 4.0 103.7 ± 7.1

Table 19: Thrombin Generation Test (TGT) in HA-PRP (Experiment B)

Thrombin generation test (TGT) for bispecific antibodies bimAb05-0745, bimAb05-3761, bimAb05-3769, bimAb05-0746, bimAb05-2112, bimAb05-2113, bimAb05-2114 and ACE910 in tissue factor-activated platelet-rich human plasma in hemophilus influenzae ii A ( PRP). Mean peak thrombin generation ± standard deviation at each test compound concentration in four independent experiments in HA-PRP (experiment B).

Experiment B
Compound concentration (nM) Peak Thrombin Level
(mean ± SD in nM)
for ACE910 Peak Thrombin Level
(mean ± SD in nM)
for bimAb05-0745 Peak Thrombin Level
(mean ± SD in nM)
for bimAb05-3761 0 15.5 ± 7.8 15.5 ± 7.8 15.5 ± 7.8 0.3 15.2 ± 7.1 12.0 ± 2.1 11.6 ± 0.7 1 16.9 ± 7.5 11.9 ± 1.4 14.0 ± 1.6 3 15.0 ± 6.9 14.5 ± 4.2 14.3 ± 3.0 10 20.3 ± 7.0 23.5 ± 5.2 18.8 ± 4.2 thirty 23.3 ± 10.3 45.0 ± 7.1 36.1 ± 6.5 100 44.3 ± 10.0 79.9 ± 10.6 65.8 ± 10.4 300 64.9 ± 12.6 106.0 ± 9.4 86.0 ± 8.6 900 94.5 ± 21.3 108.9 ± 17.0 80.8 ± 7.2 Experiment B
Compound concentration (nM) Peak Thrombin Level
(mean ± SD in nM)
for bimAb05-3769 Peak Thrombin Level
(mean ± SD in nM)
for bimAb05-0746 Peak Thrombin Level
(mean ± SD in nM)
for bimAb05-2112 0 15.5 ± 7.8 15.5 ± 7.8 15.5 ± 7.8 0.3 13.0 ± 2.6 11.3 ± 1.4 9.0 ± 2.9 1 12.6 ± 0.8 13.0 ± 2.7 12.0 ± 1.2 3 15.7 ± 3.1 13.7 ± 3.7 12.3 ± 1.1 10 24.8 ± 5.7 13.0 ± 1.2 12.9 ± 1.4 thirty 49.8 ± 10.4 15.5 ± 1.0 17.1 ± 4.8 100 95.6 ± 8.5 30.4 ± 2.8 30.8 ± 5.8 300 118.6 ± 9.6 45.3 ± 5.8 51.3 ± 6.9 900 114.4 ± 12.6 49.5 ± 5.9 83.3 ± 9.1 Experiment B
Compound concentration (nM) Peak Thrombin Level
(mean ± SD in nM)
for bimAb05-2113 Peak Thrombin Level
(mean ± SD in nM)
for bimAb05-2114 0 15.5 ± 7.8 15.5 ± 7.8 0.3 11.7 ± 1.1 11.9 ± 0.5 1 11.6 ± 1.4 12.3 ± 0.8 3 11.7 ± 0.9 12.9 ± 1.2 10 13.6 ± 2.9 15.7 ± 2.8 thirty 16.8 ± 6.1 21.3 ± 5.1 100 24.2 ± 5.2 41.9 ± 14.5 300 43.3 ± 6.2 75.8 ± 17.0 900 52.3 ± 4.1 103.7 ± 7.1

Example 17 In Vivo Efficacy of Bispecific Antibodies to FIX(a)/FX(a) in the Tail Vein Transection (TVT) Model

In vivo efficacy was determined using a tail vein transection (TVT) model in FVIII knockout mice. The efficacy of a high dose (8 mg/kg) of antibody test compounds and ACE910 was studied in a tail vein transection (TVT) study in FVIII knockout mice (B6;129S-F8tm1Kaz/J, The Jackson Laboratory, BarHarbor, ME, USA) treated together Human FIX (2 mg/kg) (Benefix, Pfizer, New York, NY, USA) and human FX (1.5 mg/kg) (Haematologic Technologies, INC, Essex Junction, VT, USA). Briefly, mice were anesthetized with isoflurane and placed on a heating pad set to maintain the animal's body temperature at 37°C while their tails were immersed in saline (37°C). The dose was administered into the right lateral tail vein 5 minutes before injury. In the present TVT model (Johansen et al., Haemophilia, 2016, 625–31), the lateral vein was dissected. If bleeding stopped after 10, 20, or 30 minutes, the tail was removed from the saline solution and the wound was gently wiped with a gauze pad soaked in saline solution. Total blood loss was determined after 40 minutes by determining the amount of hemoglobin in saline (see Table 20). The potency of the antibody test compound was compared using one-way ANOVA followed by Tukey's test for multiple comparisons. A p value of <0.05 was considered significant.

Table 20. Comparison of efficacy in bleeding models of F8 knockout mice

Bispecific Antibody ID Average blood loss
(nmol hemoglobin) Carrier medium (control) 4441 bimAb05-0745 1072* bimAb05-0746 925* bimAb05-3761 566* bimAb05-3769 860* bimAb05-2112 1301* bimAb05-2113 450* bimAb05-2114 1222* ACE910 1462*

^* Significantly different from vehicle-treated FVIII knockout mice

While certain features of the present invention have been illustrated and described herein, many modifications, substitutions, alterations and equivalents will be apparent to those of ordinary skill in the art. Accordingly, it is to be understood that the appended claims are intended to cover all such modifications and changes that fall within the true spirit of the present invention.

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LIST OF SEQUENCES

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<211> 107

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 7

Asp Ile Gln Met Thr Gln Ser Pro Ser Thr Leu Ser Ala Ser Ala Gly

1 5 10 15

Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Ser Trp

20 25 30

Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Phe Leu Ile

35 40 45

Tyr Lys Ala Ser Arg Leu Glu Arg Gly Val Pro Ser Arg Phe Ser Gly

50 55 60

Ser Gly Ser Gly Thr Glu Phe Ser Leu Thr Ile Ser Ser Leu Gln Pro

65 70 75 80

Asp Asp Phe Ala Thr Tyr Tyr Cys Leu Glu Tyr Ser Ser Tyr Ile Arg

85 90 95

Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys

100 105

<210> 8

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 8

Arg Ala Ser Gln Ser Ile Ser Ser Trp Leu Ala

1 5 10

<210> 9

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 9

Lys Ala Ser Arg Leu Glu Arg

15

<210> 10

<211> 9

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 10

Leu Glu Tyr Ser Ser Tyr Ile Arg Thr

15

<210> 11

<211> 122

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 11

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Arg

1 5 10 15

Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe His Asp Tyr

20 25 30

Ala Met His Trp Val Arg Gln Val Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Gly Ile Ser Trp Arg Gly Asp Ile Ile Gly 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 Gln Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Leu Tyr Tyr Cys

85 90 95

Val Lys Ser Tyr Gly Ser Gly Ser Phe Tyr Asn Ala Phe Asp Ser Trp

100 105 110

Gly Gln Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 12

<211> 5

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 12

Asp Tyr Ala Met His

15

<210> 13

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 13

Gly Ile Ser Trp Arg Gly Asp Ile Ile Gly Tyr Val Asp Ser Val Lys

1 5 10 15

Gly

<210> 14

<211> 13

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 14

Ser Tyr Gly Ser Gly Ser Phe Tyr Asn Ala Phe Asp Ser

1 5 10

<210> 15

<211> 107

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 15

Asp Ile Gln Met Thr Gln Ser Pro Ser Thr Leu Ser Ala Ser Ala Gly

1 5 10 15

Asp Glu Val Thr Ile Thr Cys Arg Ala Ser Lys Ser Ile Ser Ser Trp

20 25 30

Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Arg Phe Leu Ile

35 40 45

Tyr Lys Ala Ser Arg Leu Asp Arg Gly Thr Pro Ser Arg Phe Ser Gly

50 55 60

Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile Ser His Leu Gln Pro

65 70 75 80

Asp Asp Phe Ala Thr Tyr Tyr Cys Leu Glu Tyr Ser Ser Tyr Ile Arg

85 90 95

Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys

100 105

<210> 16

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 16

Arg Ala Ser Lys Ser Ile Ser Ser Trp Leu Ala

1 5 10

<210> 17

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 17

Lys Ala Ser Arg Leu Asp Arg

15

<210> 18

<211> 9

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 18

Leu Glu Tyr Ser Ser Tyr Ile Arg Thr

15

<210> 19

<211> 122

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 19

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Arg

1 5 10 15

Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asp Asp Tyr

20 25 30

Ala Met His Trp Val Arg Gln Val Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Gly Ile Ser Trp Arg Gly Asp Ile Gly Gly 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 Gln Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Leu Tyr Tyr Cys

85 90 95

Val Lys Ser Tyr Gly Ser Gly Ser Phe Tyr Asn Ala Phe Asp Ser Trp

100 105 110

Gly Gln Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 20

<211> 5

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 20

Asp Tyr Ala Met His

15

<210> 21

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 21

Gly Ile Ser Trp Arg Gly Asp Ile Gly Gly Tyr Val Asp Ser Val Lys

1 5 10 15

Gly

<210> 22

<211> 13

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 22

Ser Tyr Gly Ser Gly Ser Phe Tyr Asn Ala Phe Asp Ser

1 5 10

<210> 23

<211> 107

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 23

Asp Ile Gln Met Thr Gln Ser Pro Ser Thr Leu Ser Ala Ser Ala Gly

1 5 10 15

Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Ser Trp

20 25 30

Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Phe Leu Ile

35 40 45

Tyr Lys Ala Ser Arg Leu Asp Arg Gly Thr Pro Ser Arg Phe Ser Gly

50 55 60

Ser Gly Ser Gly Thr Glu Phe Ser Leu Thr Ile Ser Ser Leu Gln Pro

65 70 75 80

Asp Asp Phe Ala Thr Tyr Tyr Cys Leu Glu Tyr Ser Ser Tyr Ile Arg

85 90 95

Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys

100 105

<210> 24

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 24

Arg Ala Ser Gln Ser Ile Ser Ser Trp Leu Ala

1 5 10

<210> 25

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 25

Lys Ala Ser Arg Leu Asp Arg

15

<210> 26

<211> 9

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 26

Leu Glu Tyr Ser Ser Tyr Ile Arg Thr

15

<210> 27

<211> 122

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 27

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Arg

1 5 10 15

Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asp Asp Tyr

20 25 30

Ala Met His Trp Val Arg Gln Val Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Gly Ile Ser Trp Arg Gly Asp Ile Gly Gly 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 Gln Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Leu Tyr Tyr Cys

85 90 95

Val Lys Ser Tyr Gly Ser Gly Ser Phe Tyr Asn Ala Phe Asp Ser Trp

100 105 110

Gly Gln Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 28

<211> 5

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 28

Asp Tyr Ala Met His

15

<210> 29

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 29

Gly Ile Ser Trp Arg Gly Asp Ile Gly Gly Tyr Val Asp Ser Val Lys

1 5 10 15

Gly

<210> 30

<211> 13

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 30

Ser Tyr Gly Ser Gly Ser Phe Tyr Asn Ala Phe Asp Ser

1 5 10

<210> 31

<211> 107

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 31

Asp Ile Gln Met Thr Gln Ser Pro Ser Thr Leu Ser Ala Ser Val Gly

1 5 10 15

Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Ser Trp

20 25 30

Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Phe Leu Ile

35 40 45

Tyr Lys Ala Ser Arg Leu Glu Arg Gly Thr Pro Ser Arg Phe Ser Gly

50 55 60

Ser Gly Ser Gly Thr Glu Phe Ser Leu Thr Ile Ser Ser Leu Gln Pro

65 70 75 80

Asp Asp Phe Ala Thr Tyr Tyr Cys Leu Glu Tyr Ser Ser Tyr Ile Arg

85 90 95

Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys

100 105

<210> 32

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 32

Arg Ala Ser Gln Ser Ile Ser Ser Trp Leu Ala

1 5 10

<210> 33

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 33

Lys Ala Ser Arg Leu Glu Arg

15

<210> 34

<211> 9

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 34

Leu Glu Tyr Ser Ser Tyr Ile Arg Thr

15

<210> 35

<211> 122

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 35

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Arg

1 5 10 15

Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asp Asp Tyr

20 25 30

Ala Met His Trp Val Arg Gln Val Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Gly Ile Ser Trp Lys Gly Asp Ile Gly Gly 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 Gln Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Leu Tyr Tyr Cys

85 90 95

Ala Lys Ser Tyr Gly Ser Gly Ser Phe Tyr Asn Ala Phe Asp Ser Trp

100 105 110

Gly Gln Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 36

<211> 5

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 36

Asp Tyr Ala Met His

15

<210> 37

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 37

Gly Ile Ser Trp Lys Gly Asp Ile Gly Gly Tyr Val Asp Ser Val Lys

1 5 10 15

Gly

<210> 38

<211> 13

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 38

Ser Tyr Gly Ser Gly Ser Phe Tyr Asn Ala Phe Asp Ser

1 5 10

<210> 39

<211> 107

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 39

Asp Ile Gln Met Thr Gln Ser Pro Ser Thr Leu Ser Ala Ser Ala Gly

1 5 10 15

Asp Glu Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Ser Trp

20 25 30

Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile

35 40 45

Tyr Lys Ala Ser Lys Leu Asp Arg Gly Val Pro Ser Arg Phe Ser Gly

50 55 60

Ser Gly Ser Gly Thr Glu Phe Ser Leu Thr Ile Ser Asp Leu Gln Pro

65 70 75 80

Asp Asp Phe Ala Thr Tyr Tyr Cys Leu Glu Tyr Ser Ser Tyr Ile Arg

85 90 95

Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys

100 105

<210> 40

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 40

Arg Ala Ser Gln Ser Ile Ser Ser Trp Leu Ala

1 5 10

<210> 41

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 41

Lys Ala Ser Lys Leu Asp Arg

15

<210> 42

<211> 9

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 42

Leu Glu Tyr Ser Ser Tyr Ile Arg Thr

15

<210> 43

<211> 122

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 43

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Arg

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe His Asp Tyr

20 25 30

Ala Met His Trp Val Arg Gln Val Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Gly Ile Ser Trp Lys Gly Asp Ile Gly Gly Tyr Val Asp Ser Val

50 55 60

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Glu Lys Asn Ser Leu Tyr

65 70 75 80

Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Leu Tyr Tyr Cys

85 90 95

Val Lys Ser Tyr Gly Ser Gly Ser Phe Tyr Asn Ala Phe Asp Ser Trp

100 105 110

Gly Gln Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 44

<211> 5

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 44

Asp Tyr Ala Met His

15

<210> 45

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 45

Gly Ile Ser Trp Lys Gly Asp Ile Gly Gly Tyr Val Asp Ser Val Lys

1 5 10 15

Gly

<210> 46

<211> 13

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 46

Ser Tyr Gly Ser Gly Ser Phe Tyr Asn Ala Phe Asp Ser

1 5 10

<210> 47

<211> 107

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 47

Asp Ile Gln Met Thr Gln Ser Pro Ser Thr Leu Ser Ala Ser Val Gly

1 5 10 15

Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Ser Trp

20 25 30

Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile

35 40 45

Tyr Lys Ala Ser Arg Leu Glu Arg Gly Thr Pro Ser Arg Phe Ser Gly

50 55 60

Ser Gly Ser Gly Thr Glu Phe Ser Leu Thr Ile Ser Ser Leu Gln Pro

65 70 75 80

Asp Asp Phe Ala Thr Tyr Tyr Cys Leu Glu Tyr Ser Ser Tyr Ile Arg

85 90 95

Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys

100 105

<210> 48

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 48

Arg Ala Ser Gln Ser Ile Ser Ser Trp Leu Ala

1 5 10

<210> 49

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 49

Lys Ala Ser Arg Leu Glu Arg

15

<210> 50

<211> 9

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 50

Leu Glu Tyr Ser Ser Tyr Ile Arg Thr

15

<210> 51

<211> 122

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 51

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Arg

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe His Asp Tyr

20 25 30

Ala Met His Trp Val Arg Gln Val Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Gly Ile Ser Trp Arg Gly Asp Ile Gly Gly Tyr Val Lys 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 Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Leu Tyr Tyr Cys

85 90 95

Val Lys Ser Tyr Gly Ser Gly Ser Phe Tyr Asn Ala Phe Asp Ser Trp

100 105 110

Gly Gln Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 52

<211> 5

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 52

Asp Tyr Ala Met His

15

<210> 53

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 53

Gly Ile Ser Trp Arg Gly Asp Ile Gly Gly Tyr Val Lys Ser Val Lys

1 5 10 15

Gly

<210> 54

<211> 13

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 54

Ser Tyr Gly Ser Gly Ser Phe Tyr Asn Ala Phe Asp Ser

1 5 10

<210> 55

<211> 107

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 55

Asp Ile Gln Met Thr Gln Ser Pro Ser Thr Leu Ser Ala Ser Val Gly

1 5 10 15

Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Ser Trp

20 25 30

Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Phe Leu Ile

35 40 45

Tyr Lys Ala Ser Lys Leu Glu Arg Gly Thr Pro Ser Arg Phe Ser Gly

50 55 60

Ser Gly Ser Gly Thr Glu Phe Ser Leu Thr Ile Ser Ser Leu Gln Pro

65 70 75 80

Asp Asp Phe Ala Thr Tyr Tyr Cys Leu Glu Tyr Ser Ser Tyr Ile Arg

85 90 95

Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys

100 105

<210> 56

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 56

Arg Ala Ser Gln Ser Ile Ser Ser Trp Leu Ala

1 5 10

<210> 57

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 57

Lys Ala Ser Lys Leu Glu Arg

15

<210> 58

<211> 9

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 58

Leu Glu Tyr Ser Ser Tyr Ile Arg Thr

15

<210> 59

<211> 122

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 59

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Arg

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe His Asp Tyr

20 25 30

Ala Met His Trp Val Arg Gln Val Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Gly Ile Ser Trp Arg Gly Asp Ile Gly Gly Tyr Val Lys 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 Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Leu Tyr Tyr Cys

85 90 95

Val Lys Ser Tyr Gly Ser Gly Ser Phe Tyr Asn Ala Phe Asp Ser Trp

100 105 110

Gly Gln Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 60

<211> 5

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 60

Asp Tyr Ala Met His

15

<210> 61

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 61

Gly Ile Ser Trp Arg Gly Asp Ile Gly Gly Tyr Val Lys Ser Val Lys

1 5 10 15

Gly

<210> 62

<211> 13

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 62

Ser Tyr Gly Ser Gly Ser Phe Tyr Asn Ala Phe Asp Ser

1 5 10

<210> 63

<211> 107

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 63

Asp Ile Gln Met Thr Gln Ser Pro Ser Thr Leu Ser Ala Ser Val Gly

1 5 10 15

Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Ser Trp

20 25 30

Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Phe Leu Ile

35 40 45

Tyr Lys Ala Ser Arg Leu Glu Arg Gly Thr Pro Ser Arg Phe Ser Gly

50 55 60

Ser Gly Ser Gly Thr Glu Phe Ser Leu Thr Ile Ser Ser Leu Gln Pro

65 70 75 80

Asp Asp Phe Ala Thr Tyr Tyr Cys Leu Glu Tyr Ser Ser Tyr Ile Arg

85 90 95

Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys

100 105

<210> 64

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 64

Arg Ala Ser Gln Ser Ile Ser Ser Trp Leu Ala

1 5 10

<210> 65

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 65

Lys Ala Ser Arg Leu Glu Arg

15

<210> 66

<211> 9

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 66

Leu Glu Tyr Ser Ser Tyr Ile Arg Thr

15

<210> 67

<211> 122

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 67

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Arg

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe His Asp Tyr

20 25 30

Ala Met His Trp Val Arg Gln Val Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Gly Ile Ser Trp Lys Gly Asp Ile Gly Gly Tyr Val Asp Ser Val

50 55 60

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Glu Lys Asn Ser Leu Tyr

65 70 75 80

Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Leu Tyr Tyr Cys

85 90 95

Val Lys Ser Tyr Gly Ser Gly Ser Phe Tyr Asn Ala Phe Asp Ser Trp

100 105 110

Gly Gln Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 68

<211> 5

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 68

Asp Tyr Ala Met His

15

<210> 69

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 69

Gly Ile Ser Trp Lys Gly Asp Ile Gly Gly Tyr Val Asp Ser Val Lys

1 5 10 15

Gly

<210> 70

<211> 13

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 70

Ser Tyr Gly Ser Gly Ser Phe Tyr Asn Ala Phe Asp Ser

1 5 10

<210> 71

<211> 107

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 71

Asp Ile Gln Met Thr Gln Ser Pro Ser Thr Leu Ser Ala Ser Val Gly

1 5 10 15

Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Ser Trp

20 25 30

Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Phe Leu Ile

35 40 45

Tyr Lys Ala Ser Arg Leu Asp Arg Gly Thr Pro Ser Arg Phe Ser Gly

50 55 60

Ser Gly Ser Gly Thr Glu Phe Ser Leu Thr Ile Ser Ser Leu Gln Pro

65 70 75 80

Asp Asp Phe Ala Thr Tyr Tyr Cys Leu Glu Tyr Ser Ser Tyr Ile Arg

85 90 95

Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys

100 105

<210> 72

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 72

Arg Ala Ser Gln Ser Ile Ser Ser Trp Leu Ala

1 5 10

<210> 73

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 73

Lys Ala Ser Arg Leu Asp Arg

15

<210> 74

<211> 9

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 74

Leu Glu Tyr Ser Ser Tyr Ile Arg Thr

15

<210> 75

<211> 122

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 75

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Arg

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe His Asp Tyr

20 25 30

Ala Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Gly Ile Ser Trp Arg Gly Asp Ile Lys Gly 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 Gln Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Leu Tyr Tyr Cys

85 90 95

Ala Lys Ser Tyr Gly Ser Gly Ser Phe Tyr Asn Ala Phe Asp Ser Trp

100 105 110

Gly Gln Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 76

<211> 5

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 76

Asp Tyr Ala Met His

15

<210> 77

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 77

Gly Ile Ser Trp Arg Gly Asp Ile Lys Gly Tyr Val Asp Ser Val Lys

1 5 10 15

Gly

<210> 78

<211> 13

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 78

Ser Tyr Gly Ser Gly Ser Phe Tyr Asn Ala Phe Asp Ser

1 5 10

<210> 79

<211> 107

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 79

Asp Ile Gln Met Thr Gln Ser Pro Ser Thr Leu Ser Ala Ser Ala Gly

1 5 10 15

Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Lys Ser Ile Ser Ser Trp

20 25 30

Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Phe Leu Ile

35 40 45

Tyr Lys Ala Ser Arg Leu Asp Arg Gly Thr Pro Gln Arg Phe Ser Gly

50 55 60

Ser Gly Ser Gly Thr Glu Phe Ser Leu Thr Ile Ser Ser Leu Gln Pro

65 70 75 80

Asp Asp Phe Ala Thr Tyr Tyr Cys Leu Glu Tyr Ser Ser Tyr Ile Arg

85 90 95

Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys

100 105

<210> 80

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 80

Arg Ala Ser Lys Ser Ile Ser Ser Trp Leu Ala

1 5 10

<210> 81

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 81

Lys Ala Ser Arg Leu Asp Arg

15

<210> 82

<211> 9

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 82

Leu Glu Tyr Ser Ser Tyr Ile Arg Thr

15

<210> 83

<211> 122

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 83

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Arg

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe His Asp Tyr

20 25 30

Ala Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Gly Ile Ser Trp Arg Gly Asp Ile Lys Gly 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 Gln Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Leu Tyr Tyr Cys

85 90 95

Ala Lys Ser Tyr Gly Ser Gly Ser Phe Tyr Asn Ala Phe Asp Ser Trp

100 105 110

Gly Gln Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 84

<211> 5

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 84

Asp Tyr Ala Met His

15

<210> 85

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 85

Gly Ile Ser Trp Arg Gly Asp Ile Lys Gly Tyr Val Asp Ser Val Lys

1 5 10 15

Gly

<210> 86

<211> 13

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 86

Ser Tyr Gly Ser Gly Ser Phe Tyr Asn Ala Phe Asp Ser

1 5 10

<210> 87

<211> 107

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 87

Asp Ile Gln Met Thr Gln Ser Pro Ser Thr Leu Ser Ala Ser Ala Gly

1 5 10 15

Asp Arg Val Thr Ile Ser Cys Arg Ala Ser Gln Ser Ile Ser Ser Trp

20 25 30

Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile

35 40 45

Tyr Lys Ala Ser Arg Leu Asp Arg Gly Thr Pro Ser Arg Phe Ser Gly

50 55 60

Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro

65 70 75 80

Asp Asp Phe Ala Thr Tyr Tyr Cys Leu Glu Tyr Asn Ser Tyr Ile Arg

85 90 95

Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys

100 105

<210> 88

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 88

Arg Ala Ser Gln Ser Ile Ser Ser Trp Leu Ala

1 5 10

<210> 89

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 89

Lys Ala Ser Arg Leu Asp Arg

15

<210> 90

<211> 9

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 90

Leu Glu Tyr Asn Ser Tyr Ile Arg Thr

15

<210> 91

<211> 122

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 91

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Arg

1 5 10 15

Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe His Asp Tyr

20 25 30

Ala Met His Trp Val Arg Gln Val Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Gly Ile Ser Trp Arg Gly Asp Ile Gly Gly Tyr Val Lys 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 Gln Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Leu Tyr Tyr Cys

85 90 95

Val Lys Ser Tyr Gly Ser Gly Ser Phe Tyr Asn Ala Phe Asp Ser Trp

100 105 110

Gly Gln Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 92

<211> 5

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 92

Asp Tyr Ala Met His

15

<210> 93

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 93

Gly Ile Ser Trp Arg Gly Asp Ile Gly Gly Tyr Val Lys Ser Val Lys

1 5 10 15

Gly

<210> 94

<211> 13

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 94

Ser Tyr Gly Ser Gly Ser Phe Tyr Asn Ala Phe Asp Ser

1 5 10

<210> 95

<211> 107

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 95

Asp Ile Gln Met Thr Gln Ser Pro Ser Thr Leu Ser Ala Ser Val Gly

1 5 10 15

Asp Glu Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Ser Trp

20 25 30

Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Phe Leu Ile

35 40 45

Tyr Lys Ala Gln Arg Leu Asp Arg Gly Thr Pro Gln Arg Phe Ser Gly

50 55 60

Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro

65 70 75 80

Asp Asp Phe Ala Thr Tyr Tyr Cys Leu Glu Tyr Ser Ser Tyr Ile Arg

85 90 95

Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys

100 105

<210> 96

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 96

Arg Ala Ser Gln Ser Ile Ser Ser Trp Leu Ala

1 5 10

<210> 97

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 97

Lys Ala Gln Arg Leu Asp Arg

15

<210> 98

<211> 9

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 98

Leu Glu Tyr Ser Ser Tyr Ile Arg Thr

15

<210> 99

<211> 122

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 99

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Arg

1 5 10 15

Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asp Asp Tyr

20 25 30

Ala Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Gly Ile Ser Trp Lys Gly Asp Ile Gly Gly 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 Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Leu Tyr Tyr Cys

85 90 95

Val Lys Ser Tyr Gly Ser Gly Ser Phe Tyr Asn Ala Phe Asp Ser Trp

100 105 110

Gly Gln Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 100

<211> 5

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 100

Asp Tyr Ala Met His

15

<210> 101

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 101

Gly Ile Ser Trp Lys Gly Asp Ile Gly Gly Tyr Val Asp Ser Val Lys

1 5 10 15

Gly

<210> 102

<211> 13

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 102

Ser Tyr Gly Ser Gly Ser Phe Tyr Asn Ala Phe Asp Ser

1 5 10

<210> 103

<211> 107

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 103

Asp Ile Gln Met Thr Gln Ser Pro Ser Thr Leu Ser Ala Ser Ala Gly

1 5 10 15

Asp Glu Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Lys Ser Trp

20 25 30

Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Phe Leu Ile

35 40 45

Tyr Lys Ala Ser Arg Leu Asp Arg Gly Thr Pro Gln Arg Phe Ser Gly

50 55 60

Ser Gly Ser Gly Thr Glu Phe Ser Leu Thr Ile Ser Arg Leu Gln Pro

65 70 75 80

Asp Asp Phe Ala Thr Tyr Tyr Cys Leu Glu Tyr Ser Ser Tyr Ile Arg

85 90 95

Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys

100 105

<210> 104

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 104

Arg Ala Ser Gln Ser Ile Lys Ser Trp Leu Ala

1 5 10

<210> 105

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 105

Lys Ala Ser Arg Leu Asp Arg

15

<210> 106

<211> 9

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 106

Leu Glu Tyr Ser Ser Tyr Ile Arg Thr

15

<210> 107

<211> 122

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 107

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Arg

1 5 10 15

Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Arg Phe Asp Asp Tyr

20 25 30

Ala Met His Trp Val Arg Gln Val Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Gly Ile Ser Trp Lys Gly Asp Ile Gly Gly Tyr Ala 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 Gln Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Leu Tyr Tyr Cys

85 90 95

Val Lys Ser Tyr Gly Ser Gly Ser Phe Tyr Asn Ala Phe Asp Ser Trp

100 105 110

Gly Gln Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 108

<211> 5

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 108

Asp Tyr Ala Met His

15

<210> 109

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 109

Gly Ile Ser Trp Lys Gly Asp Ile Gly Gly Tyr Ala Asp Ser Val Lys

1 5 10 15

Gly

<210> 110

<211> 13

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 110

Ser Tyr Gly Ser Gly Ser Phe Tyr Asn Ala Phe Asp Ser

1 5 10

<210> 111

<211> 107

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 111

Asp Ile Gln Met Thr Gln Ser Pro Ser Thr Leu Ser Ala Ser Val Gly

1 5 10 15

Asp Glu Val Thr Ile Thr Cys Arg Ala Ser Lys Ser Ile Ser Ser Trp

20 25 30

Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Arg Phe Leu Ile

35 40 45

Tyr Lys Ala Ser Arg Leu Glu Arg Gly Thr Pro Gln Arg Phe Ser Gly

50 55 60

Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile Tyr Ser Leu Gln Pro

65 70 75 80

Asp Asp Phe Ala Thr Tyr Tyr Cys Leu Glu Tyr Ser Ser Tyr Ile Arg

85 90 95

Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys

100 105

<210> 112

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 112

Arg Ala Ser Lys Ser Ile Ser Ser Trp Leu Ala

1 5 10

<210> 113

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 113

Lys Ala Ser Arg Leu Glu Arg

15

<210> 114

<211> 9

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 114

Leu Glu Tyr Ser Ser Tyr Ile Arg Thr

15

<210> 115

<211> 122

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 115

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Arg

1 5 10 15

Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Arg Phe Asp Asp Tyr

20 25 30

Ala Met His Trp Val Arg Gln Val Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Gly Ile Ser Trp Lys Gly Asp Ile Gly Gly Tyr Ala 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 Gln Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Leu Tyr Tyr Cys

85 90 95

Val Lys Ser Tyr Gly Ser Gly Ser Phe Tyr Asn Ala Phe Asp Ser Trp

100 105 110

Gly Gln Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 116

<211> 5

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 116

Asp Tyr Ala Met His

15

<210> 117

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 117

Gly Ile Ser Trp Lys Gly Asp Ile Gly Gly Tyr Ala Asp Ser Val Lys

1 5 10 15

Gly

<210> 118

<211> 13

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 118

Ser Tyr Gly Ser Gly Ser Phe Tyr Asn Ala Phe Asp Ser

1 5 10

<210> 119

<211> 107

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 119

Asp Ile Gln Met Thr Gln Ser Pro Ser Thr Leu Ser Ala Ser Val Gly

1 5 10 15

Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Ser Trp

20 25 30

Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Phe Leu Ile

35 40 45

Tyr Lys Ala Ser Arg Leu Glu Arg Gly Thr Pro Ser Arg Phe Ser Gly

50 55 60

Ser Gly Ser Gly Thr Glu Phe Ser Leu Thr Ile Ser Ser Leu Gln Pro

65 70 75 80

Asp Asp Phe Ala Thr Tyr Tyr Cys Leu Glu Tyr Ser Ser Tyr Ile Arg

85 90 95

Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys

100 105

<210> 120

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 120

Arg Ala Ser Gln Ser Ile Ser Ser Trp Leu Ala

1 5 10

<210> 121

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 121

Lys Ala Ser Arg Leu Glu Arg

15

<210> 122

<211> 9

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 122

Leu Glu Tyr Ser Ser Tyr Ile Arg Thr

15

<210> 123

<211> 122

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 123

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Arg

1 5 10 15

Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe His Asp Tyr

20 25 30

Ala Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Gly Ile Ser Trp Lys Gly Asp Ile Gly Gly 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 Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Leu Tyr Tyr Cys

85 90 95

Ala Lys Ser Tyr Gly Ser Gly Ser Phe Tyr Asn Ala Phe Asp Ser Trp

100 105 110

Gly Gln Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 124

<211> 5

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 124

Asp Tyr Ala Met His

15

<210> 125

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 125

Gly Ile Ser Trp Lys Gly Asp Ile Gly Gly Tyr Val Asp Ser Val Lys

1 5 10 15

Gly

<210> 126

<211> 13

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 126

Ser Tyr Gly Ser Gly Ser Phe Tyr Asn Ala Phe Asp Ser

1 5 10

<210> 127

<211> 107

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 127

Asp Ile Gln Met Thr Gln Ser Pro Ser Thr Leu Ser Ala Ser Val Gly

1 5 10 15

Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Ser Trp

20 25 30

Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Phe Leu Ile

35 40 45

Tyr Lys Ala Ser Lys Leu Asp Arg Gly Thr Pro Ser Arg Phe Ser Gly

50 55 60

Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro

65 70 75 80

Asp Asp Phe Ala Thr Tyr Tyr Cys Leu Glu Tyr Ser Ser Tyr Ile Arg

85 90 95

Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys

100 105

<210> 128

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 128

Arg Ala Ser Gln Ser Ile Ser Ser Trp Leu Ala

1 5 10

<210> 129

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 129

Lys Ala Ser Lys Leu Asp Arg

15

<210> 130

<211> 9

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 130

Leu Glu Tyr Ser Ser Tyr Ile Arg Thr

15

<210> 131

<211> 122

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 131

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Arg

1 5 10 15

Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asp Asp Tyr

20 25 30

Ala Met His Trp Val Arg Gln Val Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Gly Ile Ser Trp Lys Gly Asp Ile Gly Gly 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 Gln Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Leu Tyr Tyr Cys

85 90 95

Ala Lys Ser Tyr Gly Ser Gly Ser Phe Tyr Asn Ala Phe Asp Ser Trp

100 105 110

Gly Gln Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 132

<211> 5

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 132

Asp Tyr Ala Met His

15

<210> 133

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 133

Gly Ile Ser Trp Lys Gly Asp Ile Gly Gly Tyr Val Asp Ser Val Lys

1 5 10 15

Gly

<210> 134

<211> 13

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 134

Ser Tyr Gly Ser Gly Ser Phe Tyr Asn Ala Phe Asp Ser

1 5 10

<210> 135

<211> 107

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 135

Asp Ile Gln Met Thr Gln Ser Pro Ser Thr Leu Ser Ala Ser Ala Gly

1 5 10 15

Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Ser Trp

20 25 30

Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Phe Leu Ile

35 40 45

Tyr Lys Ala Ser Arg Leu Asp Arg Gly Thr Pro Ser Arg Phe Ser Gly

50 55 60

Ser Gly Ser Gly Thr Glu Phe Ser Leu Thr Ile Ser Ser Leu Gln Pro

65 70 75 80

Asp Asp Phe Ala Thr Tyr Tyr Cys Leu Glu Tyr Ser Ser Tyr Ile Arg

85 90 95

Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys

100 105

<210> 136

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 136

Arg Ala Ser Gln Ser Ile Ser Ser Trp Leu Ala

1 5 10

<210> 137

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 137

Lys Ala Ser Arg Leu Asp Arg

15

<210> 138

<211> 9

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 138

Leu Glu Tyr Ser Ser Tyr Ile Arg Thr

15

<210> 139

<211> 122

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 139

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Arg

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe His Asp Tyr

20 25 30

Ala Met His Trp Val Arg Gln Val Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Gly Ile Ser Trp Lys Gly Asp Ile Gly Gly Tyr Val Asp Ser Val

50 55 60

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Glu Lys Asn Ser Leu Tyr

65 70 75 80

Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Leu Tyr Tyr Cys

85 90 95

Val Lys Ser Tyr Gly Ser Gly Ser Phe Tyr Asn Ala Phe Asp Ser Trp

100 105 110

Gly Gln Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 140

<211> 5

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 140

Asp Tyr Ala Met His

15

<210> 141

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 141

Gly Ile Ser Trp Lys Gly Asp Ile Gly Gly Tyr Val Asp Ser Val Lys

1 5 10 15

Gly

<210> 142

<211> 13

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 142

Ser Tyr Gly Ser Gly Ser Phe Tyr Asn Ala Phe Asp Ser

1 5 10

<210> 143

<211> 107

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 143

Asp Ile Gln Met Thr Gln Ser Pro Ser Thr Leu Ser Ala Ser Val Gly

1 5 10 15

Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Ser Trp

20 25 30

Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Phe Leu Ile

35 40 45

Tyr Lys Ala Ser Arg Leu Asp Arg Gly Cys Pro Ser Arg Phe Ser Gly

50 55 60

Ser Gly Ser Gly Thr Glu Phe Ser Leu Thr Ile Ser Ser Leu Gln Pro

65 70 75 80

Asp Asp Phe Ala Thr Tyr Tyr Cys Leu Glu Tyr Ser Ser Tyr Ile Arg

85 90 95

Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys

100 105

<210> 144

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 144

Arg Ala Ser Gln Ser Ile Ser Ser Trp Leu Ala

1 5 10

<210> 145

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 145

Lys Ala Ser Arg Leu Asp Arg

15

<210> 146

<211> 9

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 146

Leu Glu Tyr Ser Ser Tyr Ile Arg Thr

15

<210> 147

<211> 122

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 147

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Arg

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe His Asp Tyr

20 25 30

Ala Met His Trp Val Arg Gln Val Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Gly Ile Ser Trp Lys Gly Asp Ile Gly Gly Tyr Val Asp Ser Val

50 55 60

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Glu Lys Asn Ser Leu Tyr

65 70 75 80

Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Leu Tyr Tyr Cys

85 90 95

Val Lys Ser Tyr Gly Ser Gly Ser Phe Tyr Asn Ala Phe Asp Ser Trp

100 105 110

Gly Gln Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 148

<211> 5

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 148

Asp Tyr Ala Met His

15

<210> 149

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 149

Gly Ile Ser Trp Lys Gly Asp Ile Gly Gly Tyr Val Asp Ser Val Lys

1 5 10 15

Gly

<210> 150

<211> 13

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 150

Ser Tyr Gly Ser Gly Ser Phe Tyr Asn Ala Phe Asp Ser

1 5 10

<210> 151

<211> 107

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 151

Asp Ile Gln Met Thr Gln Ser Pro Ser Thr Leu Ser Ala Ser Val Gly

1 5 10 15

Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Ser Trp

20 25 30

Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Phe Leu Ile

35 40 45

Tyr Lys Ala Ser Arg Leu Asp Arg Gly Ile Pro Ser Arg Phe Ser Gly

50 55 60

Ser Gly Ser Gly Thr Glu Phe Ser Leu Thr Ile Ser Ser Leu Gln Pro

65 70 75 80

Asp Asp Phe Ala Thr Tyr Tyr Cys Leu Glu Tyr Ser Ser Tyr Ile Arg

85 90 95

Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys

100 105

<210> 152

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 152

Arg Ala Ser Gln Ser Ile Ser Ser Trp Leu Ala

1 5 10

<210> 153

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 153

Lys Ala Ser Arg Leu Asp Arg

15

<210> 154

<211> 9

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 154

Leu Glu Tyr Ser Ser Tyr Ile Arg Thr

15

<210> 155

<211> 122

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 155

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Arg

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe His Asp Tyr

20 25 30

Ala Met His Trp Val Arg Gln Val Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Gly Ile Ser Trp Lys Gly Asp Ile Gly Gly Tyr Val Asp Ser Val

50 55 60

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Glu Lys Asn Ser Leu Tyr

65 70 75 80

Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Leu Tyr Tyr Cys

85 90 95

Val Lys Ser Tyr Gly Ser Gly Ser Phe Tyr Asn Ala Phe Asp Ser Trp

100 105 110

Gly Gln Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 156

<211> 5

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 156

Asp Tyr Ala Met His

15

<210> 157

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 157

Gly Ile Ser Trp Lys Gly Asp Ile Gly Gly Tyr Val Asp Ser Val Lys

1 5 10 15

Gly

<210> 158

<211> 13

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 158

Ser Tyr Gly Ser Gly Ser Phe Tyr Asn Ala Phe Asp Ser

1 5 10

<210> 159

<211> 107

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 159

Asp Ile Gln Met Thr Gln Ser Pro Ser Thr Leu Ser Ala Ser Val Gly

1 5 10 15

Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Ser Trp

20 25 30

Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Phe Leu Ile

35 40 45

Tyr Lys Ala Ser Arg Leu Asp Arg Gly Leu Pro Ser Arg Phe Ser Gly

50 55 60

Ser Gly Ser Gly Thr Glu Phe Ser Leu Thr Ile Ser Ser Leu Gln Pro

65 70 75 80

Asp Asp Phe Ala Thr Tyr Tyr Cys Leu Glu Tyr Ser Ser Tyr Ile Arg

85 90 95

Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys

100 105

<210> 160

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 160

Arg Ala Ser Gln Ser Ile Ser Ser Trp Leu Ala

1 5 10

<210> 161

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 161

Lys Ala Ser Arg Leu Asp Arg

15

<210> 162

<211> 9

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 162

Leu Glu Tyr Ser Ser Tyr Ile Arg Thr

15

<210> 163

<211> 122

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 163

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Arg

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe His Asp Tyr

20 25 30

Ala Met His Trp Val Arg Gln Val Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Gly Ile Ser Trp Lys Gly Asp Ile Gly Gly Tyr Val Asp Ser Val

50 55 60

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Glu Lys Asn Ser Leu Tyr

65 70 75 80

Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Leu Tyr Tyr Cys

85 90 95

Val Lys Ser Tyr Gly Ser Gly Ser Phe Tyr Asn Ala Phe Asp Ser Trp

100 105 110

Gly Gln Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 164

<211> 5

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 164

Asp Tyr Ala Met His

15

<210> 165

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 165

Gly Ile Ser Trp Lys Gly Asp Ile Gly Gly Tyr Val Asp Ser Val Lys

1 5 10 15

Gly

<210> 166

<211> 13

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 166

Ser Tyr Gly Ser Gly Ser Phe Tyr Asn Ala Phe Asp Ser

1 5 10

<210> 167

<211> 107

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 167

Asp Ile Gln Met Thr Gln Ser Pro Ser Thr Leu Ser Ala Ser Val Gly

1 5 10 15

Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Ser Trp

20 25 30

Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Phe Leu Ile

35 40 45

Tyr Lys Ala Ser Arg Leu Asp Arg Gly Met Pro Ser Arg Phe Ser Gly

50 55 60

Ser Gly Ser Gly Thr Glu Phe Ser Leu Thr Ile Ser Ser Leu Gln Pro

65 70 75 80

Asp Asp Phe Ala Thr Tyr Tyr Cys Leu Glu Tyr Ser Ser Tyr Ile Arg

85 90 95

Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys

100 105

<210> 168

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 168

Arg Ala Ser Gln Ser Ile Ser Ser Trp Leu Ala

1 5 10

<210> 169

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 169

Lys Ala Ser Arg Leu Asp Arg

15

<210> 170

<211> 9

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 170

Leu Glu Tyr Ser Ser Tyr Ile Arg Thr

15

<210> 171

<211> 122

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 171

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Arg

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe His Asp Tyr

20 25 30

Ala Met His Trp Val Arg Gln Val Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Gly Ile Ser Trp Lys Gly Asp Ile Gly Gly Tyr Val Asp Ser Val

50 55 60

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Glu Lys Asn Ser Leu Tyr

65 70 75 80

Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Leu Tyr Tyr Cys

85 90 95

Val Lys Ser Tyr Gly Ser Gly Ser Phe Tyr Asn Ala Phe Asp Ser Trp

100 105 110

Gly Gln Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 172

<211> 5

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 172

Asp Tyr Ala Met His

15

<210> 173

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 173

Gly Ile Ser Trp Lys Gly Asp Ile Gly Gly Tyr Val Asp Ser Val Lys

1 5 10 15

Gly

<210> 174

<211> 13

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 174

Ser Tyr Gly Ser Gly Ser Phe Tyr Asn Ala Phe Asp Ser

1 5 10

<210> 175

<211> 107

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 175

Asp Ile Gln Met Thr Gln Ser Pro Ser Thr Leu Ser Ala Ser Val Gly

1 5 10 15

Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Ser Trp

20 25 30

Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Phe Leu Ile

35 40 45

Tyr Lys Ala Ser Arg Leu Asp Arg Gly Asn Pro Ser Arg Phe Ser Gly

50 55 60

Ser Gly Ser Gly Thr Glu Phe Ser Leu Thr Ile Ser Ser Leu Gln Pro

65 70 75 80

Asp Asp Phe Ala Thr Tyr Tyr Cys Leu Glu Tyr Ser Ser Tyr Ile Arg

85 90 95

Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys

100 105

<210> 176

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 176

Arg Ala Ser Gln Ser Ile Ser Ser Trp Leu Ala

1 5 10

<210> 177

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 177

Lys Ala Ser Arg Leu Asp Arg

15

<210> 178

<211> 9

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 178

Leu Glu Tyr Ser Ser Tyr Ile Arg Thr

15

<210> 179

<211> 122

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 179

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Arg

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe His Asp Tyr

20 25 30

Ala Met His Trp Val Arg Gln Val Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Gly Ile Ser Trp Lys Gly Asp Ile Gly Gly Tyr Val Asp Ser Val

50 55 60

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Glu Lys Asn Ser Leu Tyr

65 70 75 80

Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Leu Tyr Tyr Cys

85 90 95

Val Lys Ser Tyr Gly Ser Gly Ser Phe Tyr Asn Ala Phe Asp Ser Trp

100 105 110

Gly Gln Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 180

<211> 5

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 180

Asp Tyr Ala Met His

15

<210> 181

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 181

Gly Ile Ser Trp Lys Gly Asp Ile Gly Gly Tyr Val Asp Ser Val Lys

1 5 10 15

Gly

<210> 182

<211> 13

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 182

Ser Tyr Gly Ser Gly Ser Phe Tyr Asn Ala Phe Asp Ser

1 5 10

<210> 183

<211> 107

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 183

Asp Ile Gln Met Thr Gln Ser Pro Ser Thr Leu Ser Ala Ser Val Gly

1 5 10 15

Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Ser Trp

20 25 30

Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Phe Leu Ile

35 40 45

Tyr Lys Ala Ser Arg Leu Asp Arg Gly Gln Pro Ser Arg Phe Ser Gly

50 55 60

Ser Gly Ser Gly Thr Glu Phe Ser Leu Thr Ile Ser Ser Leu Gln Pro

65 70 75 80

Asp Asp Phe Ala Thr Tyr Tyr Cys Leu Glu Tyr Ser Ser Tyr Ile Arg

85 90 95

Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys

100 105

<210> 184

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 184

Arg Ala Ser Gln Ser Ile Ser Ser Trp Leu Ala

1 5 10

<210> 185

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 185

Lys Ala Ser Arg Leu Asp Arg

15

<210> 186

<211> 9

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 186

Leu Glu Tyr Ser Ser Tyr Ile Arg Thr

15

<210> 187

<211> 122

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 187

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Arg

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe His Asp Tyr

20 25 30

Ala Met His Trp Val Arg Gln Val Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Gly Ile Ser Trp Lys Gly Asp Ile Gly Gly Tyr Val Asp Ser Val

50 55 60

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Glu Lys Asn Ser Leu Tyr

65 70 75 80

Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Leu Tyr Tyr Cys

85 90 95

Val Lys Ser Tyr Gly Ser Gly Ser Phe Tyr Asn Ala Phe Asp Ser Trp

100 105 110

Gly Gln Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 188

<211> 5

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 188

Asp Tyr Ala Met His

15

<210> 189

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 189

Gly Ile Ser Trp Lys Gly Asp Ile Gly Gly Tyr Val Asp Ser Val Lys

1 5 10 15

Gly

<210> 190

<211> 13

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 190

Ser Tyr Gly Ser Gly Ser Phe Tyr Asn Ala Phe Asp Ser

1 5 10

<210> 191

<211> 107

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 191

Asp Ile Gln Met Thr Gln Ser Pro Ser Thr Leu Ser Ala Ser Val Gly

1 5 10 15

Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Ser Trp

20 25 30

Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Phe Leu Ile

35 40 45

Tyr Lys Ala Ser Arg Leu Asp Arg Gly Ser Pro Ser Arg Phe Ser Gly

50 55 60

Ser Gly Ser Gly Thr Glu Phe Ser Leu Thr Ile Ser Ser Leu Gln Pro

65 70 75 80

Asp Asp Phe Ala Thr Tyr Tyr Cys Leu Glu Tyr Ser Ser Tyr Ile Arg

85 90 95

Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys

100 105

<210> 192

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 192

Arg Ala Ser Gln Ser Ile Ser Ser Trp Leu Ala

1 5 10

<210> 193

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 193

Lys Ala Ser Arg Leu Asp Arg

15

<210> 194

<211> 9

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 194

Leu Glu Tyr Ser Ser Tyr Ile Arg Thr

15

<210> 195

<211> 122

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 195

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Arg

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe His Asp Tyr

20 25 30

Ala Met His Trp Val Arg Gln Val Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Gly Ile Ser Trp Lys Gly Asp Ile Gly Gly Tyr Val Asp Ser Val

50 55 60

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Glu Lys Asn Ser Leu Tyr

65 70 75 80

Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Leu Tyr Tyr Cys

85 90 95

Val Lys Ser Tyr Gly Ser Gly Ser Phe Tyr Asn Ala Phe Asp Ser Trp

100 105 110

Gly Gln Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 196

<211> 5

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 196

Asp Tyr Ala Met His

15

<210> 197

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 197

Gly Ile Ser Trp Lys Gly Asp Ile Gly Gly Tyr Val Asp Ser Val Lys

1 5 10 15

Gly

<210> 198

<211> 13

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 198

Ser Tyr Gly Ser Gly Ser Phe Tyr Asn Ala Phe Asp Ser

1 5 10

<210> 199

<211> 107

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 199

Asp Ile Gln Met Thr Gln Ser Pro Ser Thr Leu Ser Ala Ser Val Gly

1 5 10 15

Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Ser Trp

20 25 30

Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Phe Leu Ile

35 40 45

Tyr Lys Ala Ser Arg Leu Asp Arg Gly Val Pro Ser Arg Phe Ser Gly

50 55 60

Ser Gly Ser Gly Thr Glu Phe Ser Leu Thr Ile Ser Ser Leu Gln Pro

65 70 75 80

Asp Asp Phe Ala Thr Tyr Tyr Cys Leu Glu Tyr Ser Ser Tyr Ile Arg

85 90 95

Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys

100 105

<210> 200

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 200

Arg Ala Ser Gln Ser Ile Ser Ser Trp Leu Ala

1 5 10

<210> 201

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 201

Lys Ala Ser Arg Leu Asp Arg

15

<210> 202

<211> 9

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 202

Leu Glu Tyr Ser Ser Tyr Ile Arg Thr

15

<210> 203

<211> 122

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 203

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Arg

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe His Asp Tyr

20 25 30

Ala Met His Trp Val Arg Gln Val Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Gly Ile Ser Trp Lys Gly Asp Ile Gly Gly Tyr Val Asp Ser Val

50 55 60

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Glu Lys Asn Ser Leu Tyr

65 70 75 80

Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Leu Tyr Tyr Cys

85 90 95

Val Lys Ser Tyr Gly Ser Gly Ser Phe Tyr Asn Ala Phe Asp Ser Trp

100 105 110

Gly Gln Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 204

<211> 5

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 204

Asp Tyr Ala Met His

15

<210> 205

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 205

Gly Ile Ser Trp Lys Gly Asp Ile Gly Gly Tyr Val Asp Ser Val Lys

1 5 10 15

Gly

<210> 206

<211> 13

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 206

Ser Tyr Gly Ser Gly Ser Phe Tyr Asn Ala Phe Asp Ser

1 5 10

<210> 207

<211> 107

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 207

Asp Ile Gln Met Thr Gln Ser Pro Ser Thr Leu Ser Ala Ser Val Gly

1 5 10 15

Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Ser Trp

20 25 30

Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Phe Leu Ile

35 40 45

Tyr Lys Ala Ser Arg Leu Asp Arg Gly Trp Pro Ser Arg Phe Ser Gly

50 55 60

Ser Gly Ser Gly Thr Glu Phe Ser Leu Thr Ile Ser Ser Leu Gln Pro

65 70 75 80

Asp Asp Phe Ala Thr Tyr Tyr Cys Leu Glu Tyr Ser Ser Tyr Ile Arg

85 90 95

Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys

100 105

<210> 208

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 208

Arg Ala Ser Gln Ser Ile Ser Ser Trp Leu Ala

1 5 10

<210> 209

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 209

Lys Ala Ser Arg Leu Asp Arg

15

<210> 210

<211> 9

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 210

Leu Glu Tyr Ser Ser Tyr Ile Arg Thr

15

<210> 211

<211> 122

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 211

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Arg

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Lys Phe Thr Phe His Asp Tyr

20 25 30

Ala Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Gly Ile Ser Trp Lys Gly Asp Ile Gly Gly Tyr Ala 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 Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Leu Tyr Tyr Cys

85 90 95

Ala Lys Ser Tyr Gly Ser Gly Ser Phe Tyr Asn Ala Phe Asp Ser Trp

100 105 110

Gly Gln Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 212

<211> 5

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 212

Asp Tyr Ala Met His

15

<210> 213

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 213

Gly Ile Ser Trp Lys Gly Asp Ile Gly Gly Tyr Ala Asp Ser Val Lys

1 5 10 15

Gly

<210> 214

<211> 13

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 214

Ser Tyr Gly Ser Gly Ser Phe Tyr Asn Ala Phe Asp Ser

1 5 10

<210> 215

<211> 107

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 215

Asp Ile Gln Met Thr Gln Ser Pro Ser Thr Leu Ser Ala Ser Val Gly

1 5 10 15

Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Ser Trp

20 25 30

Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Phe Leu Ile

35 40 45

Tyr Lys Ala Ser Lys Leu Asp Arg Gly Thr Pro Ser Arg Phe Ser Gly

50 55 60

Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro

65 70 75 80

Asp Asp Phe Ala Thr Tyr Tyr Cys Leu Glu Tyr Ser Ser Tyr Ile Arg

85 90 95

Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys

100 105

<210> 216

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 216

Arg Ala Ser Gln Ser Ile Ser Ser Trp Leu Ala

1 5 10

<210> 217

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 217

Lys Ala Ser Lys Leu Asp Arg

15

<210> 218

<211> 9

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 218

Leu Glu Tyr Ser Ser Tyr Ile Arg Thr

15

<210> 219

<211> 122

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 219

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Arg

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Lys Phe Thr Phe His Asp Tyr

20 25 30

Ala Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Gly Ile Ser Trp Lys Gly Asp Ile Gly Gly Tyr Ala 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 Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Leu Tyr Tyr Cys

85 90 95

Ala Lys Ser Tyr Gly Ser Gly Ser Phe Tyr Asn Ala Phe Asp Ser Trp

100 105 110

Gly Gln Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 220

<211> 5

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 220

Asp Tyr Ala Met His

15

<210> 221

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 221

Gly Ile Ser Trp Lys Gly Asp Ile Gly Gly Tyr Ala Asp Ser Val Lys

1 5 10 15

Gly

<210> 222

<211> 13

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 222

Ser Tyr Gly Ser Gly Ser Phe Tyr Asn Ala Phe Asp Ser

1 5 10

<210> 223

<211> 107

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 223

Asp Ile Gln Met Thr Gln Ser Pro Ser Thr Leu Ser Ala Ser Val Gly

1 5 10 15

Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Ser Trp

20 25 30

Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Phe Leu Ile

35 40 45

Tyr Lys Ala Ser Lys Leu Glu Arg Gly Thr Pro Ser Arg Phe Ser Gly

50 55 60

Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro

65 70 75 80

Asp Asp Phe Ala Thr Tyr Tyr Cys Leu Glu Tyr Ser Ser Tyr Ile Arg

85 90 95

Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys

100 105

<210> 224

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 224

Arg Ala Ser Gln Ser Ile Ser Ser Trp Leu Ala

1 5 10

<210> 225

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 225

Lys Ala Ser Lys Leu Glu Arg

15

<210> 226

<211> 9

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 226

Leu Glu Tyr Ser Ser Tyr Ile Arg Thr

15

<210> 227

<211> 122

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 227

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Arg

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Lys Phe Thr Phe His Asp Tyr

20 25 30

Ala Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Gly Ile Ser Trp Lys Gly Asp Ile Gly Gly 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 Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Leu Tyr Tyr Cys

85 90 95

Ala Lys Ser Tyr Gly Ser Gly Ser Phe Tyr Asn Ala Phe Asp Ser Trp

100 105 110

Gly Gln Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 228

<211> 5

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 228

Asp Tyr Ala Met His

15

<210> 229

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 229

Gly Ile Ser Trp Lys Gly Asp Ile Gly Gly Tyr Val Asp Ser Val Lys

1 5 10 15

Gly

<210> 230

<211> 13

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 230

Ser Tyr Gly Ser Gly Ser Phe Tyr Asn Ala Phe Asp Ser

1 5 10

<210> 231

<211> 107

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 231

Asp Ile Gln Met Thr Gln Ser Pro Ser Thr Leu Ser Ala Ser Val Gly

1 5 10 15

Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Ser Trp

20 25 30

Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Phe Leu Ile

35 40 45

Tyr Lys Ala Ser Lys Leu Asp Arg Gly Thr Pro Ser Arg Phe Ser Gly

50 55 60

Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro

65 70 75 80

Asp Asp Phe Ala Thr Tyr Tyr Cys Leu Glu Tyr Ser Ser Tyr Ile Arg

85 90 95

Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys

100 105

<210> 232

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 232

Arg Ala Ser Gln Ser Ile Ser Ser Trp Leu Ala

1 5 10

<210> 233

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 233

Lys Ala Ser Lys Leu Asp Arg

15

<210> 234

<211> 9

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 234

Leu Glu Tyr Ser Ser Tyr Ile Arg Thr

15

<210> 235

<211> 122

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 235

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Arg

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Lys Phe Thr Phe His Asp Tyr

20 25 30

Ala Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Gly Ile Ser Trp Lys Gly Asp Ile Gly Gly 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 Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Leu Tyr Tyr Cys

85 90 95

Ala Lys Ser Tyr Gly Ser Gly Ser Phe Tyr Asn Ala Phe Asp Ser Trp

100 105 110

Gly Gln Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 236

<211> 5

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 236

Asp Tyr Ala Met His

15

<210> 237

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 237

Gly Ile Ser Trp Lys Gly Asp Ile Gly Gly Tyr Val Asp Ser Val Lys

1 5 10 15

Gly

<210> 238

<211> 13

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 238

Ser Tyr Gly Ser Gly Ser Phe Tyr Asn Ala Phe Asp Ser

1 5 10

<210> 239

<211> 107

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 239

Asp Ile Gln Met Thr Gln Ser Pro Ser Thr Leu Ser Ala Ser Val Gly

1 5 10 15

Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Ser Trp

20 25 30

Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Phe Leu Ile

35 40 45

Tyr Lys Ala Ser Lys Leu Glu Arg Gly Thr Pro Ser Arg Phe Ser Gly

50 55 60

Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro

65 70 75 80

Asp Asp Phe Ala Thr Tyr Tyr Cys Leu Glu Tyr Ser Ser Tyr Ile Arg

85 90 95

Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys

100 105

<210> 240

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 240

Arg Ala Ser Gln Ser Ile Ser Ser Trp Leu Ala

1 5 10

<210> 241

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 241

Lys Ala Ser Lys Leu Glu Arg

15

<210> 242

<211> 9

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 242

Leu Glu Tyr Ser Ser Tyr Ile Arg Thr

15

<210> 243

<211> 122

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 243

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Arg

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Lys Phe Thr Phe His Asp Tyr

20 25 30

Ala Met His Trp Val Arg Gln Val Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Gly Ile Ser Trp Lys Gly Asp Ile Gly Gly 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 Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Leu Tyr Tyr Cys

85 90 95

Ala Lys Ser Tyr Gly Ser Gly Ser Phe Tyr Asn Ala Phe Asp Ser Trp

100 105 110

Gly Gln Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 244

<211> 5

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 244

Asp Tyr Ala Met His

15

<210> 245

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 245

Gly Ile Ser Trp Lys Gly Asp Ile Gly Gly Tyr Val Asp Ser Val Lys

1 5 10 15

Gly

<210> 246

<211> 13

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 246

Ser Tyr Gly Ser Gly Ser Phe Tyr Asn Ala Phe Asp Ser

1 5 10

<210> 247

<211> 107

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 247

Asp Ile Gln Met Thr Gln Ser Pro Ser Thr Leu Ser Ala Ser Val Gly

1 5 10 15

Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Ser Trp

20 25 30

Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Phe Leu Ile

35 40 45

Tyr Lys Ala Ser Lys Leu Asp Arg Gly Thr Pro Ser Arg Phe Ser Gly

50 55 60

Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro

65 70 75 80

Asp Asp Phe Ala Thr Tyr Tyr Cys Leu Glu Tyr Ser Ser Tyr Ile Arg

85 90 95

Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys

100 105

<210> 248

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 248

Arg Ala Ser Gln Ser Ile Ser Ser Trp Leu Ala

1 5 10

<210> 249

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 249

Lys Ala Ser Lys Leu Asp Arg

15

<210> 250

<211> 9

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 250

Leu Glu Tyr Ser Ser Tyr Ile Arg Thr

15

<210> 251

<211> 122

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 251

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Arg

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Lys Phe Thr Phe His Asp Tyr

20 25 30

Ala Met His Trp Val Arg Gln Val Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Gly Ile Ser Trp Lys Gly Asp Ile Gly Gly 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 Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Leu Tyr Tyr Cys

85 90 95

Ala Lys Ser Tyr Gly Ser Gly Ser Phe Tyr Asn Ala Phe Asp Ser Trp

100 105 110

Gly Gln Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 252

<211> 5

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 252

Asp Tyr Ala Met His

15

<210> 253

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 253

Gly Ile Ser Trp Lys Gly Asp Ile Gly Gly Tyr Val Asp Ser Val Lys

1 5 10 15

Gly

<210> 254

<211> 13

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 254

Ser Tyr Gly Ser Gly Ser Phe Tyr Asn Ala Phe Asp Ser

1 5 10

<210> 255

<211> 107

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 255

Asp Ile Gln Met Thr Gln Ser Pro Ser Thr Leu Ser Ala Ser Val Gly

1 5 10 15

Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Ser Trp

20 25 30

Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Phe Leu Ile

35 40 45

Tyr Lys Ala Ser Lys Leu Glu Arg Gly Thr Pro Ser Arg Phe Ser Gly

50 55 60

Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro

65 70 75 80

Asp Asp Phe Ala Thr Tyr Tyr Cys Leu Glu Tyr Ser Ser Tyr Ile Arg

85 90 95

Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys

100 105

<210> 256

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 256

Arg Ala Ser Gln Ser Ile Ser Ser Trp Leu Ala

1 5 10

<210> 257

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 257

Lys Ala Ser Lys Leu Glu Arg

15

<210> 258

<211> 9

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 258

Leu Glu Tyr Ser Ser Tyr Ile Arg Thr

15

<210> 259

<211> 122

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 259

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Arg

1 5 10 15

Ser Leu Lys Leu Ser Cys Ala Ala Ser Lys Phe Thr Phe His Asp Tyr

20 25 30

Ala Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Gly Ile Ser Trp Lys Gly Asp Ile Gly Gly 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 Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Leu Tyr Tyr Cys

85 90 95

Ala Lys Ser Tyr Gly Ser Gly Ser Phe Tyr Asn Ala Phe Asp Ser Trp

100 105 110

Gly Gln Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 260

<211> 5

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 260

Asp Tyr Ala Met His

15

<210> 261

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 261

Gly Ile Ser Trp Lys Gly Asp Ile Gly Gly Tyr Val Asp Ser Val Lys

1 5 10 15

Gly

<210> 262

<211> 13

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 262

Ser Tyr Gly Ser Gly Ser Phe Tyr Asn Ala Phe Asp Ser

1 5 10

<210> 263

<211> 107

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 263

Asp Ile Gln Met Thr Gln Ser Pro Ser Thr Leu Ser Ala Ser Val Gly

1 5 10 15

Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Ser Trp

20 25 30

Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Phe Leu Ile

35 40 45

Tyr Lys Ala Ser Lys Leu Asp Arg Gly Thr Pro Ser Arg Phe Ser Gly

50 55 60

Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro

65 70 75 80

Asp Asp Phe Ala Thr Tyr Tyr Cys Leu Glu Tyr Ser Ser Tyr Ile Arg

85 90 95

Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys

100 105

<210> 264

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 264

Arg Ala Ser Gln Ser Ile Ser Ser Trp Leu Ala

1 5 10

<210> 265

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 265

Lys Ala Ser Lys Leu Asp Arg

15

<210> 266

<211> 9

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 266

Leu Glu Tyr Ser Ser Tyr Ile Arg Thr

15

<210> 267

<211> 122

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 267

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Arg

1 5 10 15

Ser Leu Lys Leu Ser Cys Ala Ala Ser Lys Phe Thr Phe His Asp Tyr

20 25 30

Ala Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Gly Ile Ser Trp Lys Gly Asp Ile Gly Gly 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 Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Leu Tyr Tyr Cys

85 90 95

Ala Lys Ser Tyr Gly Ser Gly Ser Phe Tyr Asn Ala Phe Asp Ser Trp

100 105 110

Gly Gln Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 268

<211> 5

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 268

Asp Tyr Ala Met His

15

<210> 269

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 269

Gly Ile Ser Trp Lys Gly Asp Ile Gly Gly Tyr Val Asp Ser Val Lys

1 5 10 15

Gly

<210> 270

<211> 13

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 270

Ser Tyr Gly Ser Gly Ser Phe Tyr Asn Ala Phe Asp Ser

1 5 10

<210> 271

<211> 107

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 271

Asp Ile Gln Met Thr Gln Ser Pro Ser Thr Leu Ser Ala Ser Val Gly

1 5 10 15

Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Ser Trp

20 25 30

Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Phe Leu Ile

35 40 45

Tyr Lys Ala Ser Lys Leu Glu Arg Gly Thr Pro Ser Arg Phe Ser Gly

50 55 60

Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro

65 70 75 80

Asp Asp Phe Ala Thr Tyr Tyr Cys Leu Glu Tyr Ser Ser Tyr Ile Arg

85 90 95

Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys

100 105

<210> 272

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 272

Arg Ala Ser Gln Ser Ile Ser Ser Trp Leu Ala

1 5 10

<210> 273

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 273

Lys Ala Ser Lys Leu Glu Arg

15

<210> 274

<211> 9

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 274

Leu Glu Tyr Ser Ser Tyr Ile Arg Thr

15

<210> 275

<211> 122

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 275

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Arg

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe His Asp Tyr

20 25 30

Ala Met His Trp Val Arg Gln Val Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Gly Ile Ser Trp Lys Gly Asp Ile Gly Gly 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 Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Leu Tyr Tyr Cys

85 90 95

Ala Lys Ser Tyr Gly Ser Gly Ser Phe Tyr Asn Ala Phe Asp Ser Trp

100 105 110

Gly Gln Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 276

<211> 5

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 276

Asp Tyr Ala Met His

15

<210> 277

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 277

Gly Ile Ser Trp Lys Gly Asp Ile Gly Gly Tyr Val Asp Ser Val Lys

1 5 10 15

Gly

<210> 278

<211> 13

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 278

Ser Tyr Gly Ser Gly Ser Phe Tyr Asn Ala Phe Asp Ser

1 5 10

<210> 279

<211> 107

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 279

Asp Ile Gln Met Thr Gln Ser Pro Ser Thr Leu Ser Ala Ser Val Gly

1 5 10 15

Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Ser Trp

20 25 30

Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Phe Leu Ile

35 40 45

Tyr Lys Ala Ser Lys Leu Asp Arg Gly Thr Pro Ser Arg Phe Ser Gly

50 55 60

Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro

65 70 75 80

Asp Asp Phe Ala Thr Tyr Tyr Cys Leu Glu Tyr Ser Ser Tyr Ile Arg

85 90 95

Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys

100 105

<210> 280

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 280

Arg Ala Ser Gln Ser Ile Ser Ser Trp Leu Ala

1 5 10

<210> 281

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 281

Lys Ala Ser Lys Leu Asp Arg

15

<210> 282

<211> 9

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 282

Leu Glu Tyr Ser Ser Tyr Ile Arg Thr

15

<210> 283

<211> 122

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 283

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Arg

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe His Asp Tyr

20 25 30

Ala Met His Trp Val Arg Gln Val Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Gly Ile Ser Trp Lys Gly Asp Ile Gly Gly 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 Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Leu Tyr Tyr Cys

85 90 95

Ala Lys Ser Tyr Gly Ser Gly Ser Phe Tyr Asn Ala Phe Asp Ser Trp

100 105 110

Gly Gln Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 284

<211> 5

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 284

Asp Tyr Ala Met His

15

<210> 285

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 285

Gly Ile Ser Trp Lys Gly Asp Ile Gly Gly Tyr Val Asp Ser Val Lys

1 5 10 15

Gly

<210> 286

<211> 13

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 286

Ser Tyr Gly Ser Gly Ser Phe Tyr Asn Ala Phe Asp Ser

1 5 10

<210> 287

<211> 107

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 287

Asp Ile Gln Met Thr Gln Ser Pro Ser Thr Leu Ser Ala Ser Val Gly

1 5 10 15

Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Ser Trp

20 25 30

Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Phe Leu Ile

35 40 45

Tyr Lys Ala Ser Lys Leu Glu Arg Gly Thr Pro Ser Arg Phe Ser Gly

50 55 60

Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro

65 70 75 80

Asp Asp Phe Ala Thr Tyr Tyr Cys Leu Glu Tyr Ser Ser Tyr Ile Arg

85 90 95

Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys

100 105

<210> 288

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 288

Arg Ala Ser Gln Ser Ile Ser Ser Trp Leu Ala

1 5 10

<210> 289

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 289

Lys Ala Ser Lys Leu Glu Arg

15

<210> 290

<211> 9

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 290

Leu Glu Tyr Ser Ser Tyr Ile Arg Thr

15

<210> 291

<211> 122

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 291

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Arg

1 5 10 15

Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe His Asp Tyr

20 25 30

Ala Met His Trp Val Arg Gln Val Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Gly Ile Ser Trp Lys Gly Asp Ile Gly Gly 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 Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Leu Tyr Tyr Cys

85 90 95

Ala Lys Ser Tyr Gly Ser Gly Ser Phe Tyr Asn Ala Phe Asp Ser Trp

100 105 110

Gly Gln Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 292

<211> 5

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 292

Asp Tyr Ala Met His

15

<210> 293

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 293

Gly Ile Ser Trp Lys Gly Asp Ile Gly Gly Tyr Val Asp Ser Val Lys

1 5 10 15

Gly

<210> 294

<211> 13

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 294

Ser Tyr Gly Ser Gly Ser Phe Tyr Asn Ala Phe Asp Ser

1 5 10

<210> 295

<211> 107

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 295

Asp Ile Gln Met Thr Gln Ser Pro Ser Thr Leu Ser Ala Ser Val Gly

1 5 10 15

Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Ser Trp

20 25 30

Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Phe Leu Ile

35 40 45

Tyr Lys Ala Ser Lys Leu Asp Arg Gly Thr Pro Ser Arg Phe Ser Gly

50 55 60

Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro

65 70 75 80

Asp Asp Phe Ala Thr Tyr Tyr Cys Leu Glu Tyr Ser Ser Tyr Ile Arg

85 90 95

Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys

100 105

<210> 296

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 296

Arg Ala Ser Gln Ser Ile Ser Ser Trp Leu Ala

1 5 10

<210> 297

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 297

Lys Ala Ser Lys Leu Asp Arg

15

<210> 298

<211> 9

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 298

Leu Glu Tyr Ser Ser Tyr Ile Arg Thr

15

<210> 299

<211> 122

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 299

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Arg

1 5 10 15

Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe His Asp Tyr

20 25 30

Ala Met His Trp Val Arg Gln Val Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Gly Ile Ser Trp Lys Gly Asp Ile Gly Gly 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 Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Leu Tyr Tyr Cys

85 90 95

Ala Lys Ser Tyr Gly Ser Gly Ser Phe Tyr Asn Ala Phe Asp Ser Trp

100 105 110

Gly Gln Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 300

<211> 5

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 300

Asp Tyr Ala Met His

15

<210> 301

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 301

Gly Ile Ser Trp Lys Gly Asp Ile Gly Gly Tyr Val Asp Ser Val Lys

1 5 10 15

Gly

<210> 302

<211> 13

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 302

Ser Tyr Gly Ser Gly Ser Phe Tyr Asn Ala Phe Asp Ser

1 5 10

<210> 303

<211> 107

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 303

Asp Ile Gln Met Thr Gln Ser Pro Ser Thr Leu Ser Ala Ser Val Gly

1 5 10 15

Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Ser Trp

20 25 30

Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Phe Leu Ile

35 40 45

Tyr Lys Ala Ser Lys Leu Glu Arg Gly Thr Pro Ser Arg Phe Ser Gly

50 55 60

Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro

65 70 75 80

Asp Asp Phe Ala Thr Tyr Tyr Cys Leu Glu Tyr Ser Ser Tyr Ile Arg

85 90 95

Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys

100 105

<210> 304

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 304

Arg Ala Ser Gln Ser Ile Ser Ser Trp Leu Ala

1 5 10

<210> 305

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 305

Lys Ala Ser Lys Leu Glu Arg

15

<210> 306

<211> 9

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 306

Leu Glu Tyr Ser Ser Tyr Ile Arg Thr

15

<210> 307

<211> 122

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 307

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Arg

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Lys Phe His Asp Tyr

20 25 30

Ala Met His Trp Val Arg Gln Val Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Gly Ile Ser Trp Lys Gly Asp Ile Gly Gly Tyr Val Asp Ser Val

50 55 60

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Glu Lys Asn Ser Leu Tyr

65 70 75 80

Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Leu Tyr Tyr Cys

85 90 95

Val Lys Ser Tyr Gly Ser Gly Ser Phe Tyr Asn Ala Phe Asp Ser Trp

100 105 110

Gly Gln Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 308

<211> 5

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 308

Asp Tyr Ala Met His

15

<210> 309

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 309

Gly Ile Ser Trp Lys Gly Asp Ile Gly Gly Tyr Val Asp Ser Val Lys

1 5 10 15

Gly

<210> 310

<211> 13

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 310

Ser Tyr Gly Ser Gly Ser Phe Tyr Asn Ala Phe Asp Ser

1 5 10

<210> 311

<211> 107

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 311

Asp Ile Gln Met Thr Gln Ser Pro Ser Thr Leu Ser Ala Ser Val Gly

1 5 10 15

Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Ser Trp

20 25 30

Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Phe Leu Ile

35 40 45

Tyr Lys Ala Ser Arg Leu Asp Arg Gly Thr Pro Ser Arg Phe Ser Gly

50 55 60

Ser Gly Ser Gly Thr Glu Phe Ser Leu Thr Ile Ser Ser Leu Gln Pro

65 70 75 80

Asp Asp Phe Ala Thr Tyr Tyr Cys Leu Glu Tyr Ser Ser Tyr Ile Arg

85 90 95

Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys

100 105

<210> 312

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 312

Arg Ala Ser Gln Ser Ile Ser Ser Trp Leu Ala

1 5 10

<210> 313

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 313

Lys Ala Ser Arg Leu Asp Arg

15

<210> 314

<211> 9

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 314

Leu Glu Tyr Ser Ser Tyr Ile Arg Thr

15

<210> 315

<211> 122

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 315

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Arg

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe His Asp Tyr

20 25 30

Ala Met His Trp Val Arg Gln Val Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Gly Ile Ser Trp Lys Gly Asp Ile Gly Gly Tyr Val Asp Ser Val

50 55 60

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Asp Lys Asn Ser Leu Tyr

65 70 75 80

Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Leu Tyr Tyr Cys

85 90 95

Val Lys Ser Tyr Gly Ser Gly Ser Phe Tyr Asn Ala Phe Asp Ser Trp

100 105 110

Gly Gln Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 316

<211> 5

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 316

Asp Tyr Ala Met His

15

<210> 317

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 317

Gly Ile Ser Trp Lys Gly Asp Ile Gly Gly Tyr Val Asp Ser Val Lys

1 5 10 15

Gly

<210> 318

<211> 13

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 318

Ser Tyr Gly Ser Gly Ser Phe Tyr Asn Ala Phe Asp Ser

1 5 10

<210> 319

<211> 107

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 319

Asp Ile Gln Met Thr Gln Ser Pro Ser Thr Leu Ser Ala Ser Val Gly

1 5 10 15

Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Ser Trp

20 25 30

Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Phe Leu Ile

35 40 45

Tyr Lys Ala Ser Arg Leu Asp Arg Gly Thr Pro Ser Arg Phe Ser Gly

50 55 60

Ser Gly Ser Gly Thr Glu Phe Ser Leu Thr Ile Ser Ser Leu Gln Pro

65 70 75 80

Asp Asp Phe Ala Thr Tyr Tyr Cys Leu Glu Tyr Ser Ser Tyr Ile Arg

85 90 95

Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys

100 105

<210> 320

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 320

Arg Ala Ser Gln Ser Ile Ser Ser Trp Leu Ala

1 5 10

<210> 321

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 321

Lys Ala Ser Arg Leu Asp Arg

15

<210> 322

<211> 9

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 322

Leu Glu Tyr Ser Ser Tyr Ile Arg Thr

15

<210> 323

<211> 122

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 323

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Arg

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe His Asp Tyr

20 25 30

Ala Met His Trp Val Arg Gln Val Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Gly Ile Ser Trp Lys Gly Asp Ile Gly Gly Tyr Val Asp Ser Val

50 55 60

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Glu Lys Asn Ser Leu Tyr

65 70 75 80

Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Leu Tyr Tyr Cys

85 90 95

Val Lys Ser Tyr Gly Ser Gly Ser Phe Tyr Asn Ala Phe Asp Ser Trp

100 105 110

Gly Gln Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 324

<211> 5

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 324

Asp Tyr Ala Met His

15

<210> 325

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 325

Gly Ile Ser Trp Lys Gly Asp Ile Gly Gly Tyr Val Asp Ser Val Lys

1 5 10 15

Gly

<210> 326

<211> 13

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 326

Ser Tyr Gly Ser Gly Ser Phe Tyr Asn Ala Phe Asp Ser

1 5 10

<210> 327

<211> 107

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 327

Asp Ile Gln Met Thr Gln Ser Pro Ser Thr Leu Ser Ala Ser Val Gly

1 5 10 15

Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Lys Ile Ser Ser Trp

20 25 30

Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Phe Leu Ile

35 40 45

Tyr Lys Ala Ser Arg Leu Asp Arg Gly Thr Pro Ser Arg Phe Ser Gly

50 55 60

Ser Gly Ser Gly Thr Glu Phe Ser Leu Thr Ile Ser Ser Leu Gln Pro

65 70 75 80

Asp Asp Phe Ala Thr Tyr Tyr Cys Leu Glu Tyr Ser Ser Tyr Ile Arg

85 90 95

Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys

100 105

<210> 328

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 328

Arg Ala Ser Gln Lys Ile Ser Ser Trp Leu Ala

1 5 10

<210> 329

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 329

Lys Ala Ser Arg Leu Asp Arg

15

<210> 330

<211> 9

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 330

Leu Glu Tyr Ser Ser Tyr Ile Arg Thr

15

<210> 331

<211> 122

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 331

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Arg

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe His Asp Tyr

20 25 30

Ala Met His Trp Val Arg Gln Val Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Gly Ile Ser Trp Lys Gly Asp Ile Gly Gly Tyr Val Asp Ser Val

50 55 60

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Glu Lys Asn Ser Leu Tyr

65 70 75 80

Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Leu Tyr Tyr Cys

85 90 95

Val Lys Ser Tyr Gly Ser Gly Ser Phe Tyr Asn Ala Phe Asp Ser Trp

100 105 110

Gly Gln Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 332

<211> 5

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 332

Asp Tyr Ala Met His

15

<210> 333

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 333

Gly Ile Ser Trp Lys Gly Asp Ile Gly Gly Tyr Val Asp Ser Val Lys

1 5 10 15

Gly

<210> 334

<211> 13

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 334

Ser Tyr Gly Ser Gly Ser Phe Tyr Asn Ala Phe Asp Ser

1 5 10

<210> 335

<211> 107

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 335

Asp Ile Gln Met Thr Gln Ser Pro Ser Thr Leu Ser Ala Ser Val Gly

1 5 10 15

Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Gln Ile Ser Ser Trp

20 25 30

Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Phe Leu Ile

35 40 45

Tyr Lys Ala Ser Arg Leu Asp Arg Gly Thr Pro Ser Arg Phe Ser Gly

50 55 60

Ser Gly Ser Gly Thr Glu Phe Ser Leu Thr Ile Ser Ser Leu Gln Pro

65 70 75 80

Asp Asp Phe Ala Thr Tyr Tyr Cys Leu Glu Tyr Ser Ser Tyr Ile Arg

85 90 95

Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys

100 105

<210> 336

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 336

Arg Ala Ser Gln Gln Ile Ser Ser Trp Leu Ala

1 5 10

<210> 337

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 337

Lys Ala Ser Arg Leu Asp Arg

15

<210> 338

<211> 9

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 338

Leu Glu Tyr Ser Ser Tyr Ile Arg Thr

15

<210> 339

<211> 122

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 339

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Arg

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe His Asp Tyr

20 25 30

Ala Met His Trp Val Arg Gln Val Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Gly Ile Ser Trp Lys Gly Asp Ile Gly Gly Tyr Val Asp Ser Val

50 55 60

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Glu Lys Asn Ser Leu Tyr

65 70 75 80

Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Leu Tyr Tyr Cys

85 90 95

Val Lys Ser Tyr Gly Ser Gly Ser Phe Tyr Asn Ala Phe Asp Ser Trp

100 105 110

Gly Gln Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 340

<211> 5

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 340

Asp Tyr Ala Met His

15

<210> 341

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 341

Gly Ile Ser Trp Lys Gly Asp Ile Gly Gly Tyr Val Asp Ser Val Lys

1 5 10 15

Gly

<210> 342

<211> 13

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 342

Ser Tyr Gly Ser Gly Ser Phe Tyr Asn Ala Phe Asp Ser

1 5 10

<210> 343

<211> 107

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 343

Asp Ile Gln Met Thr Gln Ser Pro Ser Thr Leu Ser Ala Ser Val Gly

1 5 10 15

Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Gln Ser Trp

20 25 30

Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Phe Leu Ile

35 40 45

Tyr Lys Ala Ser Arg Leu Asp Arg Gly Thr Pro Ser Arg Phe Ser Gly

50 55 60

Ser Gly Ser Gly Thr Glu Phe Ser Leu Thr Ile Ser Ser Leu Gln Pro

65 70 75 80

Asp Asp Phe Ala Thr Tyr Tyr Cys Leu Glu Tyr Ser Ser Tyr Ile Arg

85 90 95

Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys

100 105

<210> 344

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 344

Arg Ala Ser Gln Ser Ile Gln Ser Trp Leu Ala

1 5 10

<210> 345

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 345

Lys Ala Ser Arg Leu Asp Arg

15

<210> 346

<211> 9

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 346

Leu Glu Tyr Ser Ser Tyr Ile Arg Thr

15

<210> 347

<211> 122

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 347

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Arg

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe His Asp Tyr

20 25 30

Ala Met His Trp Val Arg Gln Val Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Gly Ile Ser Trp Lys Gly Asp Ile Gly Gly Tyr Val Asp Ser Val

50 55 60

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Glu Lys Asn Ser Leu Tyr

65 70 75 80

Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Leu Tyr Tyr Cys

85 90 95

Val Lys Ser Tyr Gly Ser Gly Ser Phe Tyr Asn Ala Phe Asp Ser Trp

100 105 110

Gly Gln Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 348

<211> 5

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 348

Asp Tyr Ala Met His

15

<210> 349

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 349

Gly Ile Ser Trp Lys Gly Asp Ile Gly Gly Tyr Val Asp Ser Val Lys

1 5 10 15

Gly

<210> 350

<211> 13

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 350

Ser Tyr Gly Ser Gly Ser Phe Tyr Asn Ala Phe Asp Ser

1 5 10

<210> 351

<211> 107

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 351

Asp Ile Gln Met Thr Gln Ser Pro Ser Thr Leu Ser Ala Ser Val Gly

1 5 10 15

Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Ser Trp

20 25 30

Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Phe Leu Ile

35 40 45

Tyr Lys Ala Ser Arg Leu Asp Lys Gly Thr Pro Ser Arg Phe Ser Gly

50 55 60

Ser Gly Ser Gly Thr Glu Phe Ser Leu Thr Ile Ser Ser Leu Gln Pro

65 70 75 80

Asp Asp Phe Ala Thr Tyr Tyr Cys Leu Glu Tyr Ser Ser Tyr Ile Arg

85 90 95

Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys

100 105

<210> 352

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 352

Arg Ala Ser Gln Ser Ile Ser Ser Trp Leu Ala

1 5 10

<210> 353

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 353

Lys Ala Ser Arg Leu Asp Lys

15

<210> 354

<211> 9

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 354

Leu Glu Tyr Ser Ser Tyr Ile Arg Thr

15

<210> 355

<211> 122

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 355

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Arg

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe His Asp Tyr

20 25 30

Ala Met His Trp Val Arg Gln Val Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Gly Ile Ser Trp Lys Gly Asp Ile Gly Gly Tyr Val Asp Ser Val

50 55 60

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Glu Lys Asn Ser Leu Tyr

65 70 75 80

Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Leu Tyr Tyr Cys

85 90 95

Val Lys Ser Tyr Gly Ser Gly Ser Phe Tyr Asn Ala Phe Asp Ser Trp

100 105 110

Gly Gln Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 356

<211> 5

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 356

Asp Tyr Ala Met His

15

<210> 357

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 357

Gly Ile Ser Trp Lys Gly Asp Ile Gly Gly Tyr Val Asp Ser Val Lys

1 5 10 15

Gly

<210> 358

<211> 13

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 358

Ser Tyr Gly Ser Gly Ser Phe Tyr Asn Ala Phe Asp Ser

1 5 10

<210> 359

<211> 107

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 359

Asp Ile Gln Met Thr Gln Ser Pro Ser Thr Leu Ser Ala Ser Val Gly

1 5 10 15

Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Ser Trp

20 25 30

Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Phe Leu Ile

35 40 45

Tyr Lys Ala Ser Arg Leu Asp Arg Gly Thr Pro Lys Arg Phe Ser Gly

50 55 60

Ser Gly Ser Gly Thr Glu Phe Ser Leu Thr Ile Ser Ser Leu Gln Pro

65 70 75 80

Asp Asp Phe Ala Thr Tyr Tyr Cys Leu Glu Tyr Ser Ser Tyr Ile Arg

85 90 95

Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys

100 105

<210> 360

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 360

Arg Ala Ser Gln Ser Ile Ser Ser Trp Leu Ala

1 5 10

<210> 361

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 361

Lys Ala Ser Arg Leu Asp Arg

15

<210> 362

<211> 9

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 362

Leu Glu Tyr Ser Ser Tyr Ile Arg Thr

15

<210> 363

<211> 122

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 363

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Arg

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe His Asp Tyr

20 25 30

Ala Met His Trp Val Arg Gln Val Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Gly Ile Ser Trp Lys Gly Asp Ile Gly Gly Tyr Val Asp Ser Val

50 55 60

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Glu Lys Asn Ser Leu Tyr

65 70 75 80

Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Leu Tyr Tyr Cys

85 90 95

Val Lys Ser Tyr Gly Ser Gly Ser Phe Tyr Asn Ala Phe Asp Ser Trp

100 105 110

Gly Gln Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 364

<211> 5

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 364

Asp Tyr Ala Met His

15

<210> 365

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 365

Gly Ile Ser Trp Lys Gly Asp Ile Gly Gly Tyr Val Asp Ser Val Lys

1 5 10 15

Gly

<210> 366

<211> 13

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 366

Ser Tyr Gly Ser Gly Ser Phe Tyr Asn Ala Phe Asp Ser

1 5 10

<210> 367

<211> 107

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 367

Asp Ile Gln Met Thr Gln Ser Pro Ser Thr Leu Ser Ala Ser Val Gly

1 5 10 15

Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Ser Trp

20 25 30

Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Phe Leu Ile

35 40 45

Tyr Lys Ala Ser Arg Leu Asp Arg Gly Thr Pro Ser Arg Phe Ser Gly

50 55 60

Ser Gly Ser Gly Thr Glu Phe Ser Leu Thr Ile Ser Glu Leu Gln Pro

65 70 75 80

Asp Asp Phe Ala Thr Tyr Tyr Cys Leu Glu Tyr Ser Ser Tyr Ile Arg

85 90 95

Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys

100 105

<210> 368

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 368

Arg Ala Ser Gln Ser Ile Ser Ser Trp Leu Ala

1 5 10

<210> 369

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 369

Lys Ala Ser Arg Leu Asp Arg

15

<210> 370

<211> 9

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 370

Leu Glu Tyr Ser Ser Tyr Ile Arg Thr

15

<210> 371

<211> 122

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 371

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Arg

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe His Asp Tyr

20 25 30

Ala Met His Trp Val Arg Gln Val Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Gly Ile Ser Trp Lys Gly Asp Ile Gly Gly Tyr Val Asp Ser Val

50 55 60

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Glu Lys Asn Ser Leu Tyr

65 70 75 80

Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Leu Tyr Tyr Cys

85 90 95

Val Lys Ser Tyr Gly Ser Gly Ser Phe Tyr Asn Ala Phe Asp Ser Trp

100 105 110

Gly Gln Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 372

<211> 5

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 372

Asp Tyr Ala Met His

15

<210> 373

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 373

Gly Ile Ser Trp Lys Gly Asp Ile Gly Gly Tyr Val Asp Ser Val Lys

1 5 10 15

Gly

<210> 374

<211> 13

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 374

Ser Tyr Gly Ser Gly Ser Phe Tyr Asn Ala Phe Asp Ser

1 5 10

<210> 375

<211> 107

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 375

Asp Ile Gln Met Thr Gln Ser Pro Ser Thr Leu Ser Ala Ser Val Gly

1 5 10 15

Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Ser Trp

20 25 30

Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Phe Leu Ile

35 40 45

Tyr Lys Ala Ser Arg Leu Asp Arg Gly Thr Pro Ser Arg Phe Ser Gly

50 55 60

Ser Gly Ser Gly Thr Glu Phe Ser Leu Thr Ile Ser Ser Leu Thr Pro

65 70 75 80

Asp Asp Phe Ala Thr Tyr Tyr Cys Leu Glu Tyr Ser Ser Tyr Ile Arg

85 90 95

Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys

100 105

<210> 376

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 376

Arg Ala Ser Gln Ser Ile Ser Ser Trp Leu Ala

1 5 10

<210> 377

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 377

Lys Ala Ser Arg Leu Asp Arg

15

<210> 378

<211> 9

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 378

Leu Glu Tyr Ser Ser Tyr Ile Arg Thr

15

<210> 379

<211> 122

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 379

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Arg

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe His Asp Tyr

20 25 30

Ala Met His Trp Val Arg Gln Val Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Gly Ile Ser Trp Lys Gly Asp Ile Gly Gly Tyr Val Asp Ser Val

50 55 60

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Glu Lys Asn Ser Leu Tyr

65 70 75 80

Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Leu Tyr Tyr Cys

85 90 95

Val Lys Ser Tyr Gly Ser Gly Ser Phe Tyr Asn Ala Phe Asp Ser Trp

100 105 110

Gly Gln Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 380

<211> 5

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 380

Asp Tyr Ala Met His

15

<210> 381

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 381

Gly Ile Ser Trp Lys Gly Asp Ile Gly Gly Tyr Val Asp Ser Val Lys

1 5 10 15

Gly

<210> 382

<211> 13

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 382

Ser Tyr Gly Ser Gly Ser Phe Tyr Asn Ala Phe Asp Ser

1 5 10

<210> 383

<211> 107

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 383

Asp Ile Gln Met Thr Gln Ser Pro Ser Thr Leu Ser Ala Ser Val Gly

1 5 10 15

Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Ser Trp

20 25 30

Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Phe Leu Ile

35 40 45

Tyr Lys Ala Ser Arg Leu Asp Arg Gly Thr Pro Ser Arg Phe Ser Gly

50 55 60

Ser Gly Ser Gly Thr Glu Phe Ser Leu Thr Ile Ser Ser Leu Ser Pro

65 70 75 80

Asp Asp Phe Ala Thr Tyr Tyr Cys Leu Glu Tyr Ser Ser Tyr Ile Arg

85 90 95

Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys

100 105

<210> 384

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 384

Arg Ala Ser Gln Ser Ile Ser Ser Trp Leu Ala

1 5 10

<210> 385

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 385

Lys Ala Ser Arg Leu Asp Arg

15

<210> 386

<211> 9

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 386

Leu Glu Tyr Ser Ser Tyr Ile Arg Thr

15

<210> 387

<211> 122

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 387

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Arg

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe His Asp Tyr

20 25 30

Ala Met His Trp Val Arg Gln Val Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Gly Ile Ser Trp Lys Gly Asp Ile Gly Gly Tyr Val Asp Ser Val

50 55 60

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Glu Lys Asn Ser Leu Tyr

65 70 75 80

Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Leu Tyr Tyr Cys

85 90 95

Val Lys Ser Tyr Gly Ser Gly Ser Phe Tyr Asn Ala Phe Asp Ser Trp

100 105 110

Gly Gln Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 388

<211> 5

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 388

Asp Tyr Ala Met His

15

<210> 389

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 389

Gly Ile Ser Trp Lys Gly Asp Ile Gly Gly Tyr Val Asp Ser Val Lys

1 5 10 15

Gly

<210> 390

<211> 13

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 390

Ser Tyr Gly Ser Gly Ser Phe Tyr Asn Ala Phe Asp Ser

1 5 10

<210> 391

<211> 107

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 391

Asp Ile Gln Met Thr Gln Ser Pro Ser Thr Leu Ser Ala Ser Val Gly

1 5 10 15

Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Ser Trp

20 25 30

Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Phe Leu Ile

35 40 45

Tyr Lys Ala Ser Arg Leu Asp Arg Gly Thr Pro Ser Arg Phe Ser Gly

50 55 60

Ser Gly Ser Gly Thr Glu Phe Ser Leu Thr Ile Ser Ser Leu Gln Pro

65 70 75 80

Asp Asp Phe Ala Thr Tyr Tyr Cys Leu Glu Tyr Gln Ser Tyr Ile Arg

85 90 95

Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys

100 105

<210> 392

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 392

Arg Ala Ser Gln Ser Ile Ser Ser Trp Leu Ala

1 5 10

<210> 393

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 393

Lys Ala Ser Arg Leu Asp Arg

15

<210> 394

<211> 9

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 394

Leu Glu Tyr Gln Ser Tyr Ile Arg Thr

15

<210> 395

<211> 122

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 395

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Arg

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe His Asp Tyr

20 25 30

Ala Met His Trp Val Arg Gln Val Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Gly Ile Ser Trp Lys Gly Asp Ile Gly Gly Tyr Val Asp Ser Val

50 55 60

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Glu Lys Asn Ser Leu Tyr

65 70 75 80

Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Leu Tyr Tyr Cys

85 90 95

Val Lys Ser Tyr Gly Ser Gly Ser Phe Tyr Asn Ala Phe Asp Ser Trp

100 105 110

Gly Gln Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 396

<211> 5

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 396

Asp Tyr Ala Met His

15

<210> 397

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 397

Gly Ile Ser Trp Lys Gly Asp Ile Gly Gly Tyr Val Asp Ser Val Lys

1 5 10 15

Gly

<210> 398

<211> 13

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 398

Ser Tyr Gly Ser Gly Ser Phe Tyr Asn Ala Phe Asp Ser

1 5 10

<210> 399

<211> 107

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 399

Asp Ile Gln Met Thr Gln Ser Pro Ser Thr Leu Ser Ala Ser Val Gly

1 5 10 15

Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Ser Trp

20 25 30

Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Phe Leu Ile

35 40 45

Tyr Lys Ala Ser Arg Leu Asp Arg Gly Thr Pro Ser Arg Phe Ser Gly

50 55 60

Ser Gly Ser Gly Thr Glu Phe Ser Leu Thr Ile Ser Ser Leu Gln Pro

65 70 75 80

Asp Asp Phe Ala Thr Tyr Tyr Cys Leu Glu Tyr Lys Ser Tyr Ile Arg

85 90 95

Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys

100 105

<210> 400

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 400

Arg Ala Ser Gln Ser Ile Ser Ser Trp Leu Ala

1 5 10

<210> 401

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 401

Lys Ala Ser Arg Leu Asp Arg

15

<210> 402

<211> 9

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 402

Leu Glu Tyr Lys Ser Tyr Ile Arg Thr

15

<210> 403

<211> 122

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 403

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Arg

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe His Asp Tyr

20 25 30

Ala Met His Trp Val Arg Gln Val Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Gly Ile Ser Trp Lys Gly Asp Ile Gly Gly Tyr Val Asp Ser Val

50 55 60

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Glu Lys Asn Ser Leu Tyr

65 70 75 80

Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Leu Tyr Tyr Cys

85 90 95

Val Lys Ser Tyr Gly Ser Gly Ser Phe Tyr Asn Ala Phe Asp Ser Trp

100 105 110

Gly Gln Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 404

<211> 5

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 404

Asp Tyr Ala Met His

15

<210> 405

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 405

Gly Ile Ser Trp Lys Gly Asp Ile Gly Gly Tyr Val Asp Ser Val Lys

1 5 10 15

Gly

<210> 406

<211> 13

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 406

Ser Tyr Gly Ser Gly Ser Phe Tyr Asn Ala Phe Asp Ser

1 5 10

<210> 407

<211> 107

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 407

Asp Ile Gln Met Thr Gln Ser Pro Ser Thr Leu Ser Ala Ser Val Gly

1 5 10 15

Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Ser Trp

20 25 30

Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Phe Leu Ile

35 40 45

Tyr Lys Ala Ser Arg Leu Asp Arg Gly Thr Pro Ser Arg Phe Ser Gly

50 55 60

Ser Gly Ser Gly Thr Glu Phe Ser Leu Thr Ile Ser Ser Leu Gln Pro

65 70 75 80

Asp Asp Phe Ala Thr Tyr Tyr Cys Leu Glu Tyr Ser Ser Trp Ile Arg

85 90 95

Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys

100 105

<210> 408

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 408

Arg Ala Ser Gln Ser Ile Ser Ser Trp Leu Ala

1 5 10

<210> 409

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 409

Lys Ala Ser Arg Leu Asp Arg

15

<210> 410

<211> 9

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 410

Leu Glu Tyr Ser Ser Trp Ile Arg Thr

15

<210> 411

<211> 122

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 411

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Arg

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe His Asp Tyr

20 25 30

Ala Met His Trp Val Arg Gln Val Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Gly Ile Ser Trp Lys Gly Asp Ile Gly Gly Tyr Val Asp Ser Val

50 55 60

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Glu Lys Asn Ser Leu Tyr

65 70 75 80

Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Leu Tyr Tyr Cys

85 90 95

Val Lys Ser Tyr Gly Ser Gly Ser Phe Tyr Asn Ala Phe Asp Ser Trp

100 105 110

Gly Gln Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 412

<211> 5

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 412

Asp Tyr Ala Met His

15

<210> 413

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 413

Gly Ile Ser Trp Lys Gly Asp Ile Gly Gly Tyr Val Asp Ser Val Lys

1 5 10 15

Gly

<210> 414

<211> 13

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 414

Ser Tyr Gly Ser Gly Ser Phe Tyr Asn Ala Phe Asp Ser

1 5 10

<210> 415

<211> 107

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 415

Asp Ile Gln Met Thr Gln Ser Pro Ser Thr Leu Ser Ala Ser Val Gly

1 5 10 15

Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Ser Trp

20 25 30

Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Phe Leu Ile

35 40 45

Tyr Lys Ala Ser Arg Leu Asp Arg Gly Thr Pro Ser Arg Phe Ser Gly

50 55 60

Ser Gly Ser Gly Thr Glu Phe Ser Leu Thr Ile Tyr Asp Leu Gln Pro

65 70 75 80

Asp Asp Phe Ala Thr Tyr Tyr Cys Leu Glu Tyr Arg Ser Tyr Ile Arg

85 90 95

Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys

100 105

<210> 416

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 416

Arg Ala Ser Gln Ser Ile Ser Ser Trp Leu Ala

1 5 10

<210> 417

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 417

Lys Ala Ser Arg Leu Asp Arg

15

<210> 418

<211> 9

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 418

Leu Glu Tyr Arg Ser Tyr Ile Arg Thr

15

<210> 419

<211> 122

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 419

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Arg

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe His Asp Tyr

20 25 30

Ala Met His Trp Val Arg Gln Val Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Gly Ile Ser Trp Lys Gly Asp Ile Gly Gly Tyr Val Asp Ser Val

50 55 60

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Glu Lys Asn Ser Leu Tyr

65 70 75 80

Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Leu Tyr Tyr Cys

85 90 95

Val Lys Ser Tyr Gly Ser Gly Ser Phe Tyr Asn Ala Phe Asp Ser Trp

100 105 110

Gly Gln Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 420

<211> 5

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 420

Asp Tyr Ala Met His

15

<210> 421

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 421

Gly Ile Ser Trp Lys Gly Asp Ile Gly Gly Tyr Val Asp Ser Val Lys

1 5 10 15

Gly

<210> 422

<211> 13

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 422

Ser Tyr Gly Ser Gly Ser Phe Tyr Asn Ala Phe Asp Ser

1 5 10

<210> 423

<211> 107

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 423

Asp Ile Gln Met Thr Gln Ser Pro Ser Thr Leu Ser Ala Ser Val Gly

1 5 10 15

Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Ser Trp

20 25 30

Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Phe Leu Ile

35 40 45

Tyr Lys Ala Ser Arg Leu Asp Arg Gly Thr Pro Gln Arg Phe Ser Gly

50 55 60

Ser Gly Ser Gly Thr Glu Phe Ser Leu Thr Ile Tyr Ser Leu Gln Pro

65 70 75 80

Asp Asp Phe Ala Thr Tyr Tyr Cys Leu Glu Tyr Asn Ser Tyr Ile Arg

85 90 95

Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys

100 105

<210> 424

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 424

Arg Ala Ser Gln Ser Ile Ser Ser Trp Leu Ala

1 5 10

<210> 425

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 425

Lys Ala Ser Arg Leu Asp Arg

15

<210> 426

<211> 9

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 426

Leu Glu Tyr Asn Ser Tyr Ile Arg Thr

15

<210> 427

<211> 122

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 427

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Arg

1 5 10 15

Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asp Asp Tyr

20 25 30

Ala Met His Trp Val Arg Gln Val Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Gly Ile Ser Trp Lys Gly Asp Ile Gly Gly 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 Gln Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Leu Tyr Tyr Cys

85 90 95

Ala Lys Ser Tyr Gly Ser Gly Ser Phe Tyr Asn Ala Phe Asp Ser Trp

100 105 110

Gly Gln Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 428

<211> 5

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 428

Asp Tyr Ala Met His

15

<210> 429

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 429

Gly Ile Ser Trp Lys Gly Asp Ile Gly Gly Tyr Val Asp Ser Val Lys

1 5 10 15

Gly

<210> 430

<211> 13

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 430

Ser Tyr Gly Ser Gly Ser Phe Tyr Asn Ala Phe Asp Ser

1 5 10

<210> 431

<211> 107

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 431

Asp Ile Gln Met Thr Gln Ser Pro Ser Thr Leu Ser Ala Ser Ala Gly

1 5 10 15

Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Ser Trp

20 25 30

Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Phe Leu Ile

35 40 45

Tyr Lys Ala Ser Lys Leu Asp Arg Gly Thr Pro Ser Arg Phe Ser Gly

50 55 60

Ser Gly Ser Gly Thr Glu Phe Ser Leu Thr Ile Ser Ser Leu Gln Pro

65 70 75 80

Asp Asp Phe Ala Thr Tyr Tyr Cys Leu Glu Tyr Ser Ser Tyr Ile Arg

85 90 95

Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys

100 105

<210> 432

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 432

Arg Ala Ser Gln Ser Ile Ser Ser Trp Leu Ala

1 5 10

<210> 433

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 433

Lys Ala Ser Lys Leu Asp Arg

15

<210> 434

<211> 9

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 434

Leu Glu Tyr Ser Ser Tyr Ile Arg Thr

15

<210> 435

<211> 122

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 435

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Arg

1 5 10 15

Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asp Asp Tyr

20 25 30

Ala Met His Trp Val Arg Gln Val Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Gly Ile Ser Trp Arg Gly Asp Ile Gly Gly 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 Gln Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Leu Tyr Tyr Cys

85 90 95

Val Lys Ser Tyr Gly Ser Gly Ser Phe Tyr Asn Ala Phe Asp Ser Trp

100 105 110

Gly Gln Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 436

<211> 5

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 436

Asp Tyr Ala Met His

15

<210> 437

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 437

Gly Ile Ser Trp Arg Gly Asp Ile Gly Gly Tyr Val Asp Ser Val Lys

1 5 10 15

Gly

<210> 438

<211> 13

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 438

Ser Tyr Gly Ser Gly Ser Phe Tyr Asn Ala Phe Asp Ser

1 5 10

<210> 439

<211> 107

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 439

Asp Ile Gln Met Thr Gln Ser Pro Ser Thr Leu Ser Ala Ser Ala Gly

1 5 10 15

Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Ser Trp

20 25 30

Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Phe Leu Ile

35 40 45

Tyr Lys Ala Ser Lys Leu Asp Arg Gly Thr Pro Ser Arg Phe Ser Gly

50 55 60

Ser Gly Ser Gly Thr Glu Phe Ser Leu Thr Ile Ser Ser Leu Gln Pro

65 70 75 80

Asp Asp Phe Ala Thr Tyr Tyr Cys Leu Glu Tyr Ser Ser Tyr Ile Arg

85 90 95

Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys

100 105

<210> 440

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 440

Arg Ala Ser Gln Ser Ile Ser Ser Trp Leu Ala

1 5 10

<210> 441

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 441

Lys Ala Ser Lys Leu Asp Arg

15

<210> 442

<211> 9

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 442

Leu Glu Tyr Ser Ser Tyr Ile Arg Thr

15

<210> 443

<211> 122

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 443

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Arg

1 5 10 15

Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asp Asp Tyr

20 25 30

Ala Met His Trp Val Arg Gln Val Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Gly Ile Ser Trp Arg Gly Asp Ile Gly Gly 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 Gln Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Leu Tyr Tyr Cys

85 90 95

Val Lys Ser Tyr Gly Ser Gly Ser Phe Tyr Asn Ala Phe Asp Ser Trp

100 105 110

Gly Gln Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 444

<211> 5

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 444

Asp Tyr Ala Met His

15

<210> 445

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 445

Gly Ile Ser Trp Arg Gly Asp Ile Gly Gly Tyr Val Asp Ser Val Lys

1 5 10 15

Gly

<210> 446

<211> 13

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 446

Ser Tyr Gly Ser Gly Ser Phe Tyr Asn Ala Phe Asp Ser

1 5 10

<210> 447

<211> 107

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 447

Asp Ile Gln Met Thr Gln Ser Pro Ser Thr Leu Ser Ala Ser Val Gly

1 5 10 15

Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Ser Trp

20 25 30

Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile

35 40 45

Tyr Lys Ala Ser Arg Leu Glu Arg Gly Thr Pro Ser Arg Phe Ser Gly

50 55 60

Ser Gly Ser Gly Thr Glu Phe Ser Leu Thr Ile Ser Ser Leu Gln Pro

65 70 75 80

Asp Asp Phe Ala Thr Tyr Tyr Cys Leu Glu Tyr Ser Ser Tyr Ile Arg

85 90 95

Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys

100 105

<210> 448

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 448

Arg Ala Ser Gln Ser Ile Ser Ser Trp Leu Ala

1 5 10

<210> 449

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 449

Lys Ala Ser Arg Leu Glu Arg

15

<210> 450

<211> 9

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 450

Leu Glu Tyr Ser Ser Tyr Ile Arg Thr

15

<210> 451

<211> 122

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 451

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Arg

1 5 10 15

Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe His Asp Tyr

20 25 30

Ala Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Gly Ile Ser Trp Lys Gly Asp Ile Gly Gly 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 Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Leu Tyr Tyr Cys

85 90 95

Ala Lys Ser Tyr Gly Ser Gly Ser Phe Tyr Asn Ala Phe Asp Ser Trp

100 105 110

Gly Gln Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 452

<211> 5

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 452

Asp Tyr Ala Met His

15

<210> 453

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 453

Gly Ile Ser Trp Lys Gly Asp Ile Gly Gly Tyr Val Asp Ser Val Lys

1 5 10 15

Gly

<210> 454

<211> 13

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 454

Ser Tyr Gly Ser Gly Ser Phe Tyr Asn Ala Phe Asp Ser

1 5 10

<210> 455

<211> 107

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 455

Asp Ile Gln Met Thr Gln Ser Pro Ser Thr Leu Ser Ala Ser Ala Gly

1 5 10 15

Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Ser Trp

20 25 30

Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Phe Leu Ile

35 40 45

Tyr Lys Ala Ser Arg Leu Asp Arg Gly Thr Pro Ser Arg Phe Ser Gly

50 55 60

Ser Gly Ser Gly Thr Glu Phe Ser Leu Thr Ile Ser Ser Leu Gln Pro

65 70 75 80

Asp Asp Phe Ala Thr Tyr Tyr Cys Leu Glu Tyr Ser Ser Tyr Ile Arg

85 90 95

Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys

100 105

<210> 456

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 456

Arg Ala Ser Gln Ser Ile Ser Ser Trp Leu Ala

1 5 10

<210> 457

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 457

Lys Ala Ser Arg Leu Asp Arg

15

<210> 458

<211> 9

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 458

Leu Glu Tyr Ser Ser Tyr Ile Arg Thr

15

<210> 459

<211> 120

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 459

Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Glu

1 5 10 15

Ser Leu Arg Ile Ser Cys Lys Gly Ser Gly Tyr Ser Phe Thr Thr Ser

20 25 30

Trp Ile Val Trp Val Arg Gln Met Pro Gly Lys Gly Leu Glu Trp Met

35 40 45

Gly Met Ile Asp Pro Ser Asp Ser Phe Thr Ser Tyr Ser Pro Ser Phe

50 55 60

Gln Gly His Val Thr Ile Ser Ala Asp Lys Ser Ile Ser Thr Ala Tyr

65 70 75 80

Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala Met Tyr Tyr Cys

85 90 95

Ala Arg Leu His Tyr Tyr His Ser Glu Glu Phe Asp Val Trp Gly Gln

100 105 110

Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 460

<211> 5

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 460

Thr Ser Trp Ile Val

15

<210> 461

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 461

Met Ile Asp Pro Ser Asp Ser Phe Thr Ser Tyr Ser Pro Ser Phe Gln

1 5 10 15

Gly

<210> 462

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 462

Leu His Tyr Tyr His Ser Glu Glu Phe Asp Val

1 5 10

<210> 463

<211> 109

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 463

Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly

1 5 10 15

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Ser

20 25 30

Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu

35 40 45

Ile Tyr Gly Ala Ser Ser Arg Ala Arg 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 Gln Gln Phe Gly Ser Ser Arg

85 90 95

Leu Phe Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

100 105

<210> 464

<211> 12

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 464

Arg Ala Ser Gln Ser Val Ser Ser Ser Tyr Leu Ala

1 5 10

<210> 465

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 465

Gly Ala Ser Ser Arg Ala Arg

15

<210> 466

<211> 10

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 466

Gln Gln Phe Gly Ser Ser Arg Leu Phe Thr

1 5 10

<210> 467

<211> 120

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 467

Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Glu

1 5 10 15

Ser Leu Arg Ile Ser Cys Lys Gly Ser Gly Tyr Ser Phe Ser Thr Ser

20 25 30

Trp Ile Val Trp Val Arg Gln Met Pro Gly Lys Gly Leu Glu Trp Met

35 40 45

Gly Met Ile Asp Pro Ser Asp Ser Phe Thr Ser Tyr Ser Pro Ser Phe

50 55 60

Gln Gly His Val Thr Ile Ser Ala Asp Lys Ser Ile Ser Thr Ala Tyr

65 70 75 80

Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala Met Tyr Tyr Cys

85 90 95

Ala Arg Leu His Tyr Tyr Asn Ser Glu Glu Phe Asp Val Trp Gly Gln

100 105 110

Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 468

<211> 5

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 468

Thr Ser Trp Ile Val

15

<210> 469

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 469

Met Ile Asp Pro Ser Asp Ser Phe Thr Ser Tyr Ser Pro Ser Phe Gln

1 5 10 15

Gly

<210> 470

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 470

Leu His Tyr Tyr Asn Ser Glu Glu Phe Asp Val

1 5 10

<210> 471

<211> 109

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 471

Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly

1 5 10 15

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Ser

20 25 30

Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu

35 40 45

Ile Tyr Gly Gln Ser Ser Arg Thr Arg 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 Gln Gln Phe Gly Asp Ser Gln

85 90 95

Leu Phe Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

100 105

<210> 472

<211> 12

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 472

Arg Ala Ser Gln Ser Val Ser Ser Ser Tyr Leu Ala

1 5 10

<210> 473

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 473

Gly Gln Ser Ser Arg Thr Arg

15

<210> 474

<211> 10

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 474

Gln Gln Phe Gly Asp Ser Gln Leu Phe Thr

1 5 10

<210> 475

<211> 120

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 475

Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Glu

1 5 10 15

Ser Leu Arg Ile Ser Cys Lys Gly Ser Gly Tyr Ser Phe Ser Thr Ser

20 25 30

Trp Ile Val Trp Val Arg Gln Met Pro Gly Lys Gly Leu Glu Trp Met

35 40 45

Gly Met Ile Asp Pro Ser Asp Ser Phe Thr Ser Tyr Ser Pro Ser Phe

50 55 60

Gln Gly His Val Thr Ile Ser Ala Asp Lys Ser Ile Ser Thr Ala Tyr

65 70 75 80

Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala Met Tyr Tyr Cys

85 90 95

Ala Arg Leu His Tyr Tyr Asn Ser Glu Glu Phe Asp Val Trp Gly Gln

100 105 110

Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 476

<211> 5

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 476

Thr Ser Trp Ile Val

15

<210> 477

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 477

Met Ile Asp Pro Ser Asp Ser Phe Thr Ser Tyr Ser Pro Ser Phe Gln

1 5 10 15

Gly

<210> 478

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 478

Leu His Tyr Tyr Asn Ser Glu Glu Phe Asp Val

1 5 10

<210> 479

<211> 109

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 479

Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Ala Gly

1 5 10 15

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Ser

20 25 30

Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu

35 40 45

Ile Tyr Gly Ala Ser Ser Arg Ala Arg 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 Gln Gln Phe Gly Ser Ser Arg

85 90 95

Leu Phe Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

100 105

<210> 480

<211> 12

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 480

Arg Ala Ser Gln Ser Val Ser Ser Ser Tyr Leu Ala

1 5 10

<210> 481

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 481

Gly Ala Ser Ser Arg Ala Arg

15

<210> 482

<211> 10

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 482

Gln Gln Phe Gly Ser Ser Arg Leu Phe Thr

1 5 10

<210> 483

<211> 120

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 483

Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Glu

1 5 10 15

Ser Leu Arg Ile Ser Cys Lys Gly Ser Gly Tyr Ser Phe Ser Thr Ser

20 25 30

Trp Ile Ser Trp Val Arg Gln Met Pro Gly Lys Gly Leu Glu Trp Met

35 40 45

Gly Met Ile Asp Pro Ser Asp Ser Tyr Thr Ser Tyr Ser Pro Ser Phe

50 55 60

Gln Gly His Val Thr Ile Ser Ala Asp Lys Ser Ile Ser Thr Ala Tyr

65 70 75 80

Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala Met Tyr Tyr Cys

85 90 95

Ala Arg Leu His Tyr Tyr Asn Ser Glu Glu Phe Asp Val Trp Gly Gln

100 105 110

Gly Thr Met Val Thr Val Ser Ser

115 120

<210> 484

<211> 5

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 484

Thr Ser Trp Ile Ser

15

<210> 485

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 485

Met Ile Asp Pro Ser Asp Ser Tyr Thr Ser Tyr Ser Pro Ser Phe Gln

1 5 10 15

Gly

<210> 486

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 486

Leu His Tyr Tyr Asn Ser Glu Glu Phe Asp Val

1 5 10

<210> 487

<211> 109

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 487

Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly

1 5 10 15

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Ser

20 25 30

Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu

35 40 45

Ile Tyr Gly Gln Ser Ser Arg Thr Arg 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 Gln Gln Tyr Gly Asp Ser Gln

85 90 95

Leu Phe Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

100 105

<210> 488

<211> 12

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 488

Arg Ala Ser Gln Ser Val Ser Ser Ser Tyr Leu Ala

1 5 10

<210> 489

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 489

Gly Gln Ser Ser Arg Thr Arg

15

<210> 490

<211> 10

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 490

Gln Gln Tyr Gly Asp Ser Gln Leu Phe Thr

1 5 10

<210> 491

<211> 120

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 491

Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Glu

1 5 10 15

Ser Leu Arg Ile Ser Cys Lys Gly Ser Gly Tyr Ser Phe Ser Thr Ser

20 25 30

Trp Ile Ser Trp Val Arg Gln Met Pro Gly Lys Gly Leu Glu Trp Met

35 40 45

Gly Met Ile Asp Pro Ser Asp Ser Phe Thr Ser Tyr Ser Pro Ser Phe

50 55 60

Gln Gly His Val Thr Ile Ser Ala Asp Lys Ser Ile Ser Thr Ala Tyr

65 70 75 80

Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala Met Tyr Tyr Cys

85 90 95

Ala Arg Leu His Tyr Tyr Asn Ser Glu Glu Phe Asp Val Trp Gly Gln

100 105 110

Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 492

<211> 5

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 492

Thr Ser Trp Ile Ser

15

<210> 493

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 493

Met Ile Asp Pro Ser Asp Ser Phe Thr Ser Tyr Ser Pro Ser Phe Gln

1 5 10 15

Gly

<210> 494

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 494

Leu His Tyr Tyr Asn Ser Glu Glu Phe Asp Val

1 5 10

<210> 495

<211> 109

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 495

Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly

1 5 10 15

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Ser

20 25 30

Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu

35 40 45

Ile Tyr Gly Gln Ser Ser Arg Thr Arg 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 Gln Gln Tyr Gly Asp Ser Gln

85 90 95

Leu Phe Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

100 105

<210> 496

<211> 12

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 496

Arg Ala Ser Gln Ser Val Ser Ser Ser Tyr Leu Ala

1 5 10

<210> 497

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 497

Gly Gln Ser Ser Arg Thr Arg

15

<210> 498

<211> 10

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 498

Gln Gln Tyr Gly Asp Ser Gln Leu Phe Thr

1 5 10

<210> 499

<211> 120

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 499

Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Glu

1 5 10 15

Ser Leu Arg Ile Ser Cys Lys Gly Ser Gly Tyr Ser Phe Ser Thr Ser

20 25 30

Trp Ile Ser Trp Val Arg Gln Met Pro Gly Lys Gly Leu Glu Trp Met

35 40 45

Gly Met Ile Asp Pro Ser Asp Ser Tyr Thr Ser Tyr Ser Pro Ser Phe

50 55 60

Gln Gly His Val Thr Ile Ser Ala Asp Lys Ser Ile Ser Thr Ala Tyr

65 70 75 80

Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala Met Tyr Tyr Cys

85 90 95

Ala Arg Leu His Tyr Tyr Asn Ser Glu Glu Phe Asp Val Trp Gly Gln

100 105 110

Gly Thr Met Val Thr Val Ser Ser

115 120

<210> 500

<211> 5

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 500

Thr Ser Trp Ile Ser

15

<210> 501

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 501

Met Ile Asp Pro Ser Asp Ser Tyr Thr Ser Tyr Ser Pro Ser Phe Gln

1 5 10 15

Gly

<210> 502

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 502

Leu His Tyr Tyr Asn Ser Glu Glu Phe Asp Val

1 5 10

<210> 503

<211> 109

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 503

Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly

1 5 10 15

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Ser

20 25 30

Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu

35 40 45

Ile Tyr Gly Gln Ser Ser Arg Thr Arg 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 Gln Gln Phe Gly Asp Ser Gln

85 90 95

Leu Phe Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

100 105

<210> 504

<211> 12

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 504

Arg Ala Ser Gln Ser Val Ser Ser Ser Tyr Leu Ala

1 5 10

<210> 505

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 505

Gly Gln Ser Ser Arg Thr Arg

15

<210> 506

<211> 10

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 506

Gln Gln Phe Gly Asp Ser Gln Leu Phe Thr

1 5 10

<210> 507

<211> 120

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 507

Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Glu

1 5 10 15

Ser Leu Arg Ile Ser Cys Lys Gly Ser Gly Tyr Ser Phe Thr Thr Ser

20 25 30

Trp Ile Ser Trp Val Arg Gln Met Pro Gly Lys Gly Leu Glu Trp Met

35 40 45

Gly Met Ile Asp Pro Ser Asp Ser Phe Thr Ser Tyr Ser Pro Ser Phe

50 55 60

Gln Gly His Val Thr Ile Ser Ala Asp Lys Ser Ile Ser Thr Ala Tyr

65 70 75 80

Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala Met Tyr Tyr Cys

85 90 95

Ala Arg Leu His Tyr Tyr His Ser Glu Glu Phe Asp Val Trp Gly Gln

100 105 110

Gly Thr Met Val Thr Val Ser Ser

115 120

<210> 508

<211> 5

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 508

Thr Ser Trp Ile Ser

15

<210> 509

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 509

Met Ile Asp Pro Ser Asp Ser Phe Thr Ser Tyr Ser Pro Ser Phe Gln

1 5 10 15

Gly

<210> 510

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 510

Leu His Tyr Tyr His Ser Glu Glu Phe Asp Val

1 5 10

<210> 511

<211> 109

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 511

Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly

1 5 10 15

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Ser

20 25 30

Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu

35 40 45

Ile Tyr Gly Gln Ser Ser Arg Thr Arg 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 Gln Gln Phe Gly Asp Ser Gln

85 90 95

Leu Phe Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

100 105

<210> 512

<211> 12

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 512

Arg Ala Ser Gln Ser Val Ser Ser Ser Tyr Leu Ala

1 5 10

<210> 513

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 513

Gly Gln Ser Ser Arg Thr Arg

15

<210> 514

<211> 10

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 514

Gln Gln Phe Gly Asp Ser Gln Leu Phe Thr

1 5 10

<210> 515

<211> 120

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 515

Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Glu

1 5 10 15

Ser Leu Arg Ile Ser Cys Lys Gly Ser Gly Tyr Ser Phe Thr Thr Ser

20 25 30

Trp Ile Ser Trp Val Arg Gln Met Pro Gly Lys Gly Leu Glu Trp Met

35 40 45

Gly Met Ile Asp Pro Ser Asp Ser Tyr Thr Ser Tyr Ser Pro Ser Phe

50 55 60

Gln Gly His Val Thr Ile Ser Ala Asp Lys Ser Ile Ser Thr Ala Tyr

65 70 75 80

Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala Met Tyr Tyr Cys

85 90 95

Ala Arg Leu His Tyr Tyr His Ser Glu Glu Phe Asp Val Trp Gly Gln

100 105 110

Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 516

<211> 5

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 516

Thr Ser Trp Ile Ser

15

<210> 517

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 517

Met Ile Asp Pro Ser Asp Ser Tyr Thr Ser Tyr Ser Pro Ser Phe Gln

1 5 10 15

Gly

<210> 518

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 518

Leu His Tyr Tyr His Ser Glu Glu Phe Asp Val

1 5 10

<210> 519

<211> 109

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 519

Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly

1 5 10 15

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Ser

20 25 30

Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu

35 40 45

Ile Tyr Gly Gln Ser Ser Arg Thr Arg 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 Gln Gln Phe Gly Asp Ser Gln

85 90 95

Leu Phe Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

100 105

<210> 520

<211> 12

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 520

Arg Ala Ser Gln Ser Val Ser Ser Ser Tyr Leu Ala

1 5 10

<210> 521

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 521

Gly Gln Ser Ser Arg Thr Arg

15

<210> 522

<211> 10

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 522

Gln Gln Phe Gly Asp Ser Gln Leu Phe Thr

1 5 10

<210> 523

<211> 120

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 523

Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Glu

1 5 10 15

Ser Leu Arg Ile Ser Cys Lys Gly Ser Gly Tyr Ser Phe Thr Thr Ser

20 25 30

Trp Ile Ser Trp Val Arg Gln Met Pro Gly Lys Gly Leu Glu Trp Met

35 40 45

Gly Met Ile Asp Pro Ser Asp Ser Tyr Thr Ser Tyr Ser Pro Ser Phe

50 55 60

Gln Gly His Val Thr Ile Ser Ala Asp Lys Ser Ile Ser Thr Ala Tyr

65 70 75 80

Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala Met Tyr Tyr Cys

85 90 95

Ala Arg Leu His Tyr Tyr His Ser Glu Glu Phe Asp Val Trp Gly Gln

100 105 110

Gly Thr Met Val Thr Val Ser Ser

115 120

<210> 524

<211> 5

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 524

Thr Ser Trp Ile Ser

15

<210> 525

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 525

Met Ile Asp Pro Ser Asp Ser Tyr Thr Ser Tyr Ser Pro Ser Phe Gln

1 5 10 15

Gly

<210> 526

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 526

Leu His Tyr Tyr His Ser Glu Glu Phe Asp Val

1 5 10

<210> 527

<211> 109

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 527

Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly

1 5 10 15

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Ser

20 25 30

Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu

35 40 45

Ile Tyr Gly Gln Ser Ser Arg Thr Arg 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 Gln Gln Phe Gly Asp Ser Gln

85 90 95

Leu Phe Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

100 105

<210> 528

<211> 12

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 528

Arg Ala Ser Gln Ser Val Ser Ser Ser Tyr Leu Ala

1 5 10

<210> 529

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 529

Gly Gln Ser Ser Arg Thr Arg

15

<210> 530

<211> 10

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 530

Gln Gln Phe Gly Asp Ser Gln Leu Phe Thr

1 5 10

<210> 531

<211> 120

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 531

Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Glu

1 5 10 15

Ser Leu Arg Ile Ser Cys Lys Gly Ser Gly Tyr Ser Phe Ser Thr Ser

20 25 30

Trp Ile Ser Trp Val Arg Gln Met Pro Gly Lys Gly Leu Glu Trp Met

35 40 45

Gly Met Ile Asp Pro Ser Asp Ser Phe Thr Ser Tyr Ser Pro Ser Phe

50 55 60

Gln Gly His Val Thr Ile Ser Ala Asp Lys Ser Ile Ser Thr Ala Tyr

65 70 75 80

Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala Met Tyr Tyr Cys

85 90 95

Ala Arg Leu His Tyr Tyr Asn Ser Glu Glu Phe Asp Val Trp Gly Gln

100 105 110

Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 532

<211> 5

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 532

Thr Ser Trp Ile Ser

15

<210> 533

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 533

Met Ile Asp Pro Ser Asp Ser Phe Thr Ser Tyr Ser Pro Ser Phe Gln

1 5 10 15

Gly

<210> 534

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 534

Leu His Tyr Tyr Asn Ser Glu Glu Phe Asp Val

1 5 10

<210> 535

<211> 109

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 535

Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly

1 5 10 15

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Ser

20 25 30

Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu

35 40 45

Ile Tyr Gly Gln Ser Ser Arg Thr Arg 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 Gln Gln Phe Gly Asp Ser Gln

85 90 95

Leu Phe Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

100 105

<210> 536

<211> 12

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 536

Arg Ala Ser Gln Ser Val Ser Ser Ser Tyr Leu Ala

1 5 10

<210> 537

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 537

Gly Gln Ser Ser Arg Thr Arg

15

<210> 538

<211> 10

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 538

Gln Gln Phe Gly Asp Ser Gln Leu Phe Thr

1 5 10

<210> 539

<211> 120

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 539

Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Glu

1 5 10 15

Ser Leu Arg Ile Ser Cys Lys Gly Ser Gly Tyr Ser Phe Ser Thr Ser

20 25 30

Trp Ile Val Trp Val Arg Gln Met Pro Gly Lys Gly Leu Glu Trp Met

35 40 45

Gly Met Ile Asp Pro Ser Asp Ser Tyr Thr Ser Tyr Ser Pro Ser Phe

50 55 60

Gln Gly His Val Thr Ile Ser Ala Asp Lys Ser Ile Ser Thr Ala Tyr

65 70 75 80

Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala Met Tyr Tyr Cys

85 90 95

Ala Arg Leu His Tyr Tyr Asn Ser Glu Glu Phe Asp Val Trp Gly Gln

100 105 110

Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 540

<211> 5

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 540

Thr Ser Trp Ile Val

15

<210> 541

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 541

Met Ile Asp Pro Ser Asp Ser Tyr Thr Ser Tyr Ser Pro Ser Phe Gln

1 5 10 15

Gly

<210> 542

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 542

Leu His Tyr Tyr Asn Ser Glu Glu Phe Asp Val

1 5 10

<210> 543

<211> 109

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 543

Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly

1 5 10 15

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Ser

20 25 30

Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu

35 40 45

Ile Tyr Gly Gln Ser Ser Arg Thr Arg 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 Gln Gln Phe Gly Asp Ser Gln

85 90 95

Leu Phe Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

100 105

<210> 544

<211> 12

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 544

Arg Ala Ser Gln Ser Val Ser Ser Ser Tyr Leu Ala

1 5 10

<210> 545

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 545

Gly Gln Ser Ser Arg Thr Arg

15

<210> 546

<211> 10

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 546

Gln Gln Phe Gly Asp Ser Gln Leu Phe Thr

1 5 10

<210> 547

<211> 120

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 547

Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Glu

1 5 10 15

Ser Leu Arg Ile Ser Cys Lys Gly Ser Gly Tyr Ser Phe Ser Thr Ser

20 25 30

Trp Ile Val Trp Val Arg Gln Met Pro Gly Lys Gly Leu Glu Trp Met

35 40 45

Gly Met Ile Asp Pro Ser Asp Ser Tyr Thr Ser Tyr Ser Pro Ser Phe

50 55 60

Gln Gly His Val Thr Ile Ser Ala Asp Lys Ser Ile Ser Thr Ala Tyr

65 70 75 80

Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala Met Tyr Tyr Cys

85 90 95

Ala Arg Leu His Tyr Tyr Asn Ser Glu Glu Phe Asp Val Trp Gly Gln

100 105 110

Gly Thr Met Val Thr Val Ser Ser

115 120

<210> 548

<211> 5

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 548

Thr Ser Trp Ile Val

15

<210> 549

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 549

Met Ile Asp Pro Ser Asp Ser Tyr Thr Ser Tyr Ser Pro Ser Phe Gln

1 5 10 15

Gly

<210> 550

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 550

Leu His Tyr Tyr Asn Ser Glu Glu Phe Asp Val

1 5 10

<210> 551

<211> 109

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 551

Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly

1 5 10 15

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Ser

20 25 30

Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu

35 40 45

Ile Tyr Gly Gln Ser Ser Arg Thr Arg 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 Gln Gln Phe Gly Asp Ser Gln

85 90 95

Leu Phe Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

100 105

<210> 552

<211> 12

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 552

Arg Ala Ser Gln Ser Val Ser Ser Ser Tyr Leu Ala

1 5 10

<210> 553

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 553

Gly Gln Ser Ser Arg Thr Arg

15

<210> 554

<211> 10

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 554

Gln Gln Phe Gly Asp Ser Gln Leu Phe Thr

1 5 10

<210> 555

<211> 120

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 555

Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Glu

1 5 10 15

Ser Leu Arg Ile Ser Cys Lys Gly Ser Gly Tyr Ser Phe Ser Thr Ser

20 25 30

Trp Ile Val Trp Val Arg Gln Met Pro Gly Lys Gly Leu Glu Trp Met

35 40 45

Gly Met Ile Asp Pro Ser Asp Ser Phe Thr Ser Tyr Ser Pro Ser Phe

50 55 60

Gln Gly His Val Thr Ile Ser Ala Asp Lys Ser Ile Ser Thr Ala Tyr

65 70 75 80

Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala Met Tyr Tyr Cys

85 90 95

Ala Arg Leu His Tyr Tyr Asn Ser Glu Glu Phe Asp Val Trp Gly Gln

100 105 110

Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 556

<211> 5

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 556

Thr Ser Trp Ile Val

15

<210> 557

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 557

Met Ile Asp Pro Ser Asp Ser Phe Thr Ser Tyr Ser Pro Ser Phe Gln

1 5 10 15

Gly

<210> 558

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 558

Leu His Tyr Tyr Asn Ser Glu Glu Phe Asp Val

1 5 10

<210> 559

<211> 109

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 559

Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly

1 5 10 15

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Ser

20 25 30

Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu

35 40 45

Ile Tyr Gly Gln Ser Ser Arg Thr Arg 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 Gln Gln Tyr Gly Asp Ser Gln

85 90 95

Leu Phe Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

100 105

<210> 560

<211> 12

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 560

Arg Ala Ser Gln Ser Val Ser Ser Ser Tyr Leu Ala

1 5 10

<210> 561

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 561

Gly Gln Ser Ser Arg Thr Arg

15

<210> 562

<211> 10

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 562

Gln Gln Tyr Gly Asp Ser Gln Leu Phe Thr

1 5 10

<210> 563

<211> 120

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 563

Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Glu

1 5 10 15

Ser Leu Arg Ile Ser Cys Lys Gly Ser Gly Tyr Ser Phe Thr Thr Ser

20 25 30

Trp Ile Ser Trp Val Arg Gln Met Pro Gly Lys Gly Leu Glu Trp Met

35 40 45

Gly Met Ile Asp Pro Ser Asp Ser Phe Thr Ser Tyr Ser Pro Ser Phe

50 55 60

Gln Gly His Val Thr Ile Ser Ala Asp Lys Ser Ile Ser Thr Ala Tyr

65 70 75 80

Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala Met Tyr Tyr Cys

85 90 95

Ala Arg Leu His Tyr Tyr His Ser Glu Glu Phe Asp Val Trp Gly Gln

100 105 110

Gly Thr Met Val Thr Val Ser Ser

115 120

<210> 564

<211> 5

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 564

Thr Ser Trp Ile Ser

15

<210> 565

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 565

Met Ile Asp Pro Ser Asp Ser Phe Thr Ser Tyr Ser Pro Ser Phe Gln

1 5 10 15

Gly

<210> 566

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 566

Leu His Tyr Tyr His Ser Glu Glu Phe Asp Val

1 5 10

<210> 567

<211> 109

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 567

Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly

1 5 10 15

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Ser

20 25 30

Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu

35 40 45

Ile Tyr Gly Gln Ser Ser Arg Thr Arg 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 Gln Gln Tyr Gly Asp Ser Gln

85 90 95

Leu Phe Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

100 105

<210> 568

<211> 12

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 568

Arg Ala Ser Gln Ser Val Ser Ser Ser Tyr Leu Ala

1 5 10

<210> 569

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 569

Gly Gln Ser Ser Arg Thr Arg

15

<210> 570

<211> 10

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 570

Gln Gln Tyr Gly Asp Ser Gln Leu Phe Thr

1 5 10

<210> 571

<211> 120

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 571

Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Glu

1 5 10 15

Ser Leu Arg Ile Ser Cys Lys Gly Ser Gly Tyr Ser Phe Thr Thr Ser

20 25 30

Trp Ile Ser Trp Val Arg Gln Met Pro Gly Lys Gly Leu Glu Trp Met

35 40 45

Gly Met Ile Asp Pro Ser Asp Ser Tyr Thr Ser Tyr Ser Pro Ser Phe

50 55 60

Gln Gly His Val Thr Ile Ser Ala Asp Lys Ser Ile Ser Thr Ala Tyr

65 70 75 80

Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala Met Tyr Tyr Cys

85 90 95

Ala Arg Leu His Tyr Tyr His Ser Glu Glu Phe Asp Val Trp Gly Gln

100 105 110

Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 572

<211> 5

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 572

Thr Ser Trp Ile Ser

15

<210> 573

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 573

Met Ile Asp Pro Ser Asp Ser Tyr Thr Ser Tyr Ser Pro Ser Phe Gln

1 5 10 15

Gly

<210> 574

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 574

Leu His Tyr Tyr His Ser Glu Glu Phe Asp Val

1 5 10

<210> 575

<211> 109

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 575

Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly

1 5 10 15

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Ser

20 25 30

Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu

35 40 45

Ile Tyr Gly Gln Ser Ser Arg Thr Arg 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 Gln Gln Tyr Gly Asp Ser Gln

85 90 95

Leu Phe Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

100 105

<210> 576

<211> 12

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 576

Arg Ala Ser Gln Ser Val Ser Ser Ser Tyr Leu Ala

1 5 10

<210> 577

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 577

Gly Gln Ser Ser Arg Thr Arg

15

<210> 578

<211> 10

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 578

Gln Gln Tyr Gly Asp Ser Gln Leu Phe Thr

1 5 10

<210> 579

<211> 120

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 579

Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Glu

1 5 10 15

Ser Leu Arg Ile Ser Cys Lys Gly Ser Gly Tyr Ser Phe Thr Thr Ser

20 25 30

Trp Ile Ser Trp Val Arg Gln Met Pro Gly Lys Gly Leu Glu Trp Met

35 40 45

Gly Met Ile Asp Pro Ser Asp Ser Tyr Thr Ser Tyr Ser Pro Ser Phe

50 55 60

Gln Gly His Val Thr Ile Ser Ala Asp Lys Ser Ile Ser Thr Ala Tyr

65 70 75 80

Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala Met Tyr Tyr Cys

85 90 95

Ala Arg Leu His Tyr Tyr His Ser Glu Glu Phe Asp Val Trp Gly Gln

100 105 110

Gly Thr Met Val Thr Val Ser Ser

115 120

<210> 580

<211> 5

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 580

Thr Ser Trp Ile Ser

15

<210> 581

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 581

Met Ile Asp Pro Ser Asp Ser Tyr Thr Ser Tyr Ser Pro Ser Phe Gln

1 5 10 15

Gly

<210> 582

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 582

Leu His Tyr Tyr His Ser Glu Glu Phe Asp Val

1 5 10

<210> 583

<211> 109

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 583

Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly

1 5 10 15

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Ser

20 25 30

Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu

35 40 45

Ile Tyr Gly Gln Ser Ser Arg Thr Arg 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 Gln Gln Tyr Gly Asp Ser Gln

85 90 95

Leu Phe Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

100 105

<210> 584

<211> 12

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 584

Arg Ala Ser Gln Ser Val Ser Ser Ser Tyr Leu Ala

1 5 10

<210> 585

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 585

Gly Gln Ser Ser Arg Thr Arg

15

<210> 586

<211> 10

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 586

Gln Gln Tyr Gly Asp Ser Gln Leu Phe Thr

1 5 10

<210> 587

<211> 120

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 587

Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Glu

1 5 10 15

Ser Leu Arg Ile Ser Cys Lys Gly Ser Gly Tyr Ser Phe Ser Thr Ser

20 25 30

Trp Ile Val Trp Val Arg Gln Met Pro Gly Lys Gly Leu Glu Trp Met

35 40 45

Gly Met Ile Asp Pro Ser Asp Ser Tyr Thr Ser Tyr Ser Pro Ser Phe

50 55 60

Gln Gly His Val Thr Ile Ser Ala Asp Lys Ser Ile Ser Thr Ala Tyr

65 70 75 80

Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala Met Tyr Tyr Cys

85 90 95

Ala Arg Leu His Tyr Tyr Asn Ser Glu Glu Phe Asp Val Trp Gly Gln

100 105 110

Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 588

<211> 5

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 588

Thr Ser Trp Ile Val

15

<210> 589

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 589

Met Ile Asp Pro Ser Asp Ser Tyr Thr Ser Tyr Ser Pro Ser Phe Gln

1 5 10 15

Gly

<210> 590

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 590

Leu His Tyr Tyr Asn Ser Glu Glu Phe Asp Val

1 5 10

<210> 591

<211> 109

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 591

Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly

1 5 10 15

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Ser

20 25 30

Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu

35 40 45

Ile Tyr Gly Gln Ser Ser Arg Thr Arg 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 Gln Gln Tyr Gly Asp Ser Gln

85 90 95

Leu Phe Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

100 105

<210> 592

<211> 12

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 592

Arg Ala Ser Gln Ser Val Ser Ser Ser Tyr Leu Ala

1 5 10

<210> 593

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 593

Gly Gln Ser Ser Arg Thr Arg

15

<210> 594

<211> 10

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 594

Gln Gln Tyr Gly Asp Ser Gln Leu Phe Thr

1 5 10

<210> 595

<211> 120

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 595

Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Glu

1 5 10 15

Ser Leu Arg Ile Ser Cys Lys Gly Ser Gly Tyr Ser Phe Ser Thr Ser

20 25 30

Trp Ile Val Trp Val Arg Gln Met Pro Gly Lys Gly Leu Glu Trp Met

35 40 45

Gly Met Ile Asp Pro Ser Asp Ser Phe Thr Ser Tyr Ser Pro Ser Phe

50 55 60

Gln Gly His Val Thr Ile Ser Ala Asp Lys Ser Ile Ser Thr Ala Tyr

65 70 75 80

Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala Met Tyr Tyr Cys

85 90 95

Ala Arg Leu His Tyr Tyr Asn Ser Glu Glu Phe Asp Val Trp Gly Gln

100 105 110

Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 596

<211> 5

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 596

Thr Ser Trp Ile Val

15

<210> 597

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 597

Met Ile Asp Pro Ser Asp Ser Phe Thr Ser Tyr Ser Pro Ser Phe Gln

1 5 10 15

Gly

<210> 598

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 598

Leu His Tyr Tyr Asn Ser Glu Glu Phe Asp Val

1 5 10

<210> 599

<211> 109

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 599

Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly

1 5 10 15

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Ser

20 25 30

Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu

35 40 45

Ile Tyr Gly Ala Ser Ser Arg Ala Arg 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 Gln Gln Tyr Gly Asp Ser Arg

85 90 95

Leu Phe Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

100 105

<210> 600

<211> 12

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 600

Arg Ala Ser Gln Ser Val Ser Ser Ser Tyr Leu Ala

1 5 10

<210> 601

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 601

Gly Ala Ser Ser Arg Ala Arg

15

<210> 602

<211> 10

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 602

Gln Gln Tyr Gly Asp Ser Arg Leu Phe Thr

1 5 10

<210> 603

<211> 120

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 603

Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Glu

1 5 10 15

Ser Leu Arg Ile Ser Cys Lys Gly Ser Gly Tyr Ser Phe Ser Thr Ser

20 25 30

Trp Ile Ser Trp Val Arg Gln Met Pro Gly Lys Gly Leu Glu Trp Met

35 40 45

Gly Met Ile Asp Pro Ser Asp Ser Tyr Thr Ser Tyr Ser Pro Ser Phe

50 55 60

Gln Gly His Val Thr Ile Ser Ala Asp Lys Ser Ile Ser Thr Ala Tyr

65 70 75 80

Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala Met Tyr Tyr Cys

85 90 95

Ala Arg Leu His Tyr Tyr Asn Ser Glu Glu Phe Asp Val Trp Gly Gln

100 105 110

Gly Thr Met Val Thr Val Ser Ser

115 120

<210> 604

<211> 5

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 604

Thr Ser Trp Ile Ser

15

<210> 605

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 605

Met Ile Asp Pro Ser Asp Ser Tyr Thr Ser Tyr Ser Pro Ser Phe Gln

1 5 10 15

Gly

<210> 606

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 606

Leu His Tyr Tyr Asn Ser Glu Glu Phe Asp Val

1 5 10

<210> 607

<211> 109

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 607

Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly

1 5 10 15

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Ser

20 25 30

Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu

35 40 45

Ile Tyr Gly Ala Ser Ser Arg Ala Arg 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 Gln Gln Tyr Gly Asp Ser Arg

85 90 95

Leu Phe Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

100 105

<210> 608

<211> 12

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 608

Arg Ala Ser Gln Ser Val Ser Ser Ser Tyr Leu Ala

1 5 10

<210> 609

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 609

Gly Ala Ser Ser Arg Ala Arg

15

<210> 610

<211> 10

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 610

Gln Gln Tyr Gly Asp Ser Arg Leu Phe Thr

1 5 10

<210> 611

<211> 120

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 611

Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Glu

1 5 10 15

Ser Leu Arg Ile Ser Cys Lys Gly Ser Gly Tyr Ser Phe Thr Thr Ser

20 25 30

Trp Ile Ser Trp Val Arg Gln Met Pro Gly Lys Gly Leu Glu Trp Met

35 40 45

Gly Met Ile Asp Pro Ser Asp Ser Phe Thr Ser Tyr Ser Pro Ser Phe

50 55 60

Gln Gly His Val Thr Ile Ser Ala Asp Lys Ser Ile Ser Thr Ala Tyr

65 70 75 80

Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala Met Tyr Tyr Cys

85 90 95

Ala Arg Leu His Tyr Tyr His Ser Glu Glu Phe Asp Val Trp Gly Gln

100 105 110

Gly Thr Met Val Thr Val Ser Ser

115 120

<210> 612

<211> 5

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 612

Thr Ser Trp Ile Ser

15

<210> 613

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 613

Met Ile Asp Pro Ser Asp Ser Phe Thr Ser Tyr Ser Pro Ser Phe Gln

1 5 10 15

Gly

<210> 614

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 614

Leu His Tyr Tyr His Ser Glu Glu Phe Asp Val

1 5 10

<210> 615

<211> 109

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 615

Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly

1 5 10 15

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Ser

20 25 30

Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu

35 40 45

Ile Tyr Gly Ala Ser Ser Arg Ala Arg 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 Gln Gln Tyr Gly Asp Ser Arg

85 90 95

Leu Phe Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

100 105

<210> 616

<211> 12

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 616

Arg Ala Ser Gln Ser Val Ser Ser Ser Tyr Leu Ala

1 5 10

<210> 617

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 617

Gly Ala Ser Ser Arg Ala Arg

15

<210> 618

<211> 10

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 618

Gln Gln Tyr Gly Asp Ser Arg Leu Phe Thr

1 5 10

<210> 619

<211> 120

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 619

Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Glu

1 5 10 15

Ser Leu Arg Ile Ser Cys Lys Gly Ser Gly Tyr Ser Phe Thr Thr Ser

20 25 30

Trp Ile Ser Trp Val Arg Gln Met Pro Gly Lys Gly Leu Glu Trp Met

35 40 45

Gly Met Ile Asp Pro Ser Asp Ser Tyr Thr Ser Tyr Ser Pro Ser Phe

50 55 60

Gln Gly His Val Thr Ile Ser Ala Asp Lys Ser Ile Ser Thr Ala Tyr

65 70 75 80

Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala Met Tyr Tyr Cys

85 90 95

Ala Arg Leu His Tyr Tyr His Ser Glu Glu Phe Asp Val Trp Gly Gln

100 105 110

Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 620

<211> 5

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 620

Thr Ser Trp Ile Ser

15

<210> 621

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 621

Met Ile Asp Pro Ser Asp Ser Tyr Thr Ser Tyr Ser Pro Ser Phe Gln

1 5 10 15

Gly

<210> 622

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 622

Leu His Tyr Tyr His Ser Glu Glu Phe Asp Val

1 5 10

<210> 623

<211> 109

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 623

Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly

1 5 10 15

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Ser

20 25 30

Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu

35 40 45

Ile Tyr Gly Ala Ser Ser Arg Ala Arg 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 Gln Gln Tyr Gly Asp Ser Arg

85 90 95

Leu Phe Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

100 105

<210> 624

<211> 12

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 624

Arg Ala Ser Gln Ser Val Ser Ser Ser Tyr Leu Ala

1 5 10

<210> 625

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 625

Gly Ala Ser Ser Arg Ala Arg

15

<210> 626

<211> 10

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 626

Gln Gln Tyr Gly Asp Ser Arg Leu Phe Thr

1 5 10

<210> 627

<211> 120

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 627

Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Glu

1 5 10 15

Ser Leu Arg Ile Ser Cys Lys Gly Ser Gly Tyr Ser Phe Thr Thr Ser

20 25 30

Trp Ile Ser Trp Val Arg Gln Met Pro Gly Lys Gly Leu Glu Trp Met

35 40 45

Gly Met Ile Asp Pro Ser Asp Ser Tyr Thr Ser Tyr Ser Pro Ser Phe

50 55 60

Gln Gly His Val Thr Ile Ser Ala Asp Lys Ser Ile Ser Thr Ala Tyr

65 70 75 80

Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala Met Tyr Tyr Cys

85 90 95

Ala Arg Leu His Tyr Tyr His Ser Glu Glu Phe Asp Val Trp Gly Gln

100 105 110

Gly Thr Met Val Thr Val Ser Ser

115 120

<210> 628

<211> 5

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 628

Thr Ser Trp Ile Ser

15

<210> 629

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 629

Met Ile Asp Pro Ser Asp Ser Tyr Thr Ser Tyr Ser Pro Ser Phe Gln

1 5 10 15

Gly

<210> 630

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 630

Leu His Tyr Tyr His Ser Glu Glu Phe Asp Val

1 5 10

<210> 631

<211> 109

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 631

Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly

1 5 10 15

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Ser

20 25 30

Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu

35 40 45

Ile Tyr Gly Ala Ser Ser Arg Ala Arg 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 Gln Gln Tyr Gly Asp Ser Arg

85 90 95

Leu Phe Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

100 105

<210> 632

<211> 12

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 632

Arg Ala Ser Gln Ser Val Ser Ser Ser Tyr Leu Ala

1 5 10

<210> 633

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 633

Gly Ala Ser Ser Arg Ala Arg

15

<210> 634

<211> 10

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 634

Gln Gln Tyr Gly Asp Ser Arg Leu Phe Thr

1 5 10

<210> 635

<211> 120

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 635

Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Glu

1 5 10 15

Ser Leu Arg Ile Ser Cys Lys Gly Ser Gly Tyr Ser Phe Ser Thr Ser

20 25 30

Trp Ile Ser Trp Val Arg Gln Met Pro Gly Lys Gly Leu Glu Trp Met

35 40 45

Gly Met Ile Asp Pro Ser Asp Ser Phe Thr Ser Tyr Ser Pro Ser Phe

50 55 60

Gln Gly His Val Thr Ile Ser Ala Asp Lys Ser Ile Ser Thr Ala Tyr

65 70 75 80

Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala Met Tyr Tyr Cys

85 90 95

Ala Arg Leu His Tyr Tyr Asn Ser Glu Glu Phe Asp Val Trp Gly Gln

100 105 110

Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 636

<211> 5

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 636

Thr Ser Trp Ile Ser

15

<210> 637

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 637

Met Ile Asp Pro Ser Asp Ser Phe Thr Ser Tyr Ser Pro Ser Phe Gln

1 5 10 15

Gly

<210> 638

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 638

Leu His Tyr Tyr Asn Ser Glu Glu Phe Asp Val

1 5 10

<210> 639

<211> 109

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 639

Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly

1 5 10 15

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Ser

20 25 30

Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu

35 40 45

Ile Tyr Gly Ala Ser Ser Arg Ala Arg 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 Gln Gln Tyr Gly Asp Ser Arg

85 90 95

Leu Phe Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

100 105

<210> 640

<211> 12

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 640

Arg Ala Ser Gln Ser Val Ser Ser Ser Tyr Leu Ala

1 5 10

<210> 641

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 641

Gly Ala Ser Ser Arg Ala Arg

15

<210> 642

<211> 10

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 642

Gln Gln Tyr Gly Asp Ser Arg Leu Phe Thr

1 5 10

<210> 643

<211> 120

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 643

Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Glu

1 5 10 15

Ser Leu Arg Ile Ser Cys Lys Gly Ser Gly Tyr Ser Phe Ser Thr Ser

20 25 30

Trp Ile Val Trp Val Arg Gln Met Pro Gly Lys Gly Leu Glu Trp Met

35 40 45

Gly Met Ile Asp Pro Ser Asp Ser Tyr Thr Ser Tyr Ser Pro Ser Phe

50 55 60

Gln Gly His Val Thr Ile Ser Ala Asp Lys Ser Ile Ser Thr Ala Tyr

65 70 75 80

Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala Met Tyr Tyr Cys

85 90 95

Ala Arg Leu His Tyr Tyr Asn Ser Glu Glu Phe Asp Val Trp Gly Gln

100 105 110

Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 644

<211> 5

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 644

Thr Ser Trp Ile Val

15

<210> 645

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 645

Met Ile Asp Pro Ser Asp Ser Tyr Thr Ser Tyr Ser Pro Ser Phe Gln

1 5 10 15

Gly

<210> 646

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 646

Leu His Tyr Tyr Asn Ser Glu Glu Phe Asp Val

1 5 10

<210> 647

<211> 109

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 647

Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly

1 5 10 15

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Ser

20 25 30

Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu

35 40 45

Ile Tyr Gly Ala Ser Ser Arg Ala Arg 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 Gln Gln Tyr Gly Asp Ser Arg

85 90 95

Leu Phe Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

100 105

<210> 648

<211> 12

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 648

Arg Ala Ser Gln Ser Val Ser Ser Ser Tyr Leu Ala

1 5 10

<210> 649

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 649

Gly Ala Ser Ser Arg Ala Arg

15

<210> 650

<211> 10

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 650

Gln Gln Tyr Gly Asp Ser Arg Leu Phe Thr

1 5 10

<210> 651

<211> 120

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 651

Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Glu

1 5 10 15

Ser Leu Arg Ile Ser Cys Lys Gly Ser Gly Tyr Ser Phe Ser Thr Ser

20 25 30

Trp Ile Val Trp Val Arg Gln Met Pro Gly Lys Gly Leu Glu Trp Met

35 40 45

Gly Met Ile Asp Pro Ser Asp Ser Phe Thr Ser Tyr Ser Pro Ser Phe

50 55 60

Gln Gly His Val Thr Ile Ser Ala Asp Lys Ser Ile Ser Thr Ala Tyr

65 70 75 80

Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala Met Tyr Tyr Cys

85 90 95

Ala Arg Leu His Tyr Tyr Asn Ser Glu Glu Phe Asp Val Trp Gly Gln

100 105 110

Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 652

<211> 5

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 652

Thr Ser Trp Ile Val

15

<210> 653

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 653

Met Ile Asp Pro Ser Asp Ser Phe Thr Ser Tyr Ser Pro Ser Phe Gln

1 5 10 15

Gly

<210> 654

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 654

Leu His Tyr Tyr Asn Ser Glu Glu Phe Asp Val

1 5 10

<210> 655

<211> 109

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 655

Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly

1 5 10 15

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Ser

20 25 30

Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu

35 40 45

Ile Tyr Gly Gln Ser Ser Arg Thr Arg 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 Gln Gln Phe Gly Asp Ser Arg

85 90 95

Leu Phe Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

100 105

<210> 656

<211> 12

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 656

Arg Ala Ser Gln Ser Val Ser Ser Ser Tyr Leu Ala

1 5 10

<210> 657

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 657

Gly Gln Ser Ser Arg Thr Arg

15

<210> 658

<211> 10

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 658

Gln Gln Phe Gly Asp Ser Arg Leu Phe Thr

1 5 10

<210> 659

<211> 120

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 659

Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Glu

1 5 10 15

Ser Leu Arg Ile Ser Cys Lys Gly Ser Gly Tyr Ser Phe Ser Thr Ser

20 25 30

Trp Ile Ser Trp Val Arg Gln Met Pro Gly Lys Gly Leu Glu Trp Met

35 40 45

Gly Met Ile Asp Pro Ser Asp Ser Tyr Thr Ser Tyr Ser Pro Ser Phe

50 55 60

Gln Gly His Val Thr Ile Ser Ala Asp Lys Ser Ile Ser Thr Ala Tyr

65 70 75 80

Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala Met Tyr Tyr Cys

85 90 95

Ala Arg Leu His Tyr Tyr Asn Ser Glu Glu Phe Asp Val Trp Gly Gln

100 105 110

Gly Thr Met Val Thr Val Ser Ser

115 120

<210> 660

<211> 5

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 660

Thr Ser Trp Ile Ser

15

<210> 661

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 661

Met Ile Asp Pro Ser Asp Ser Tyr Thr Ser Tyr Ser Pro Ser Phe Gln

1 5 10 15

Gly

<210> 662

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 662

Leu His Tyr Tyr Asn Ser Glu Glu Phe Asp Val

1 5 10

<210> 663

<211> 109

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 663

Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly

1 5 10 15

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Ser

20 25 30

Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu

35 40 45

Ile Tyr Gly Gln Ser Ser Arg Thr Arg 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 Gln Gln Phe Gly Asp Ser Arg

85 90 95

Leu Phe Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

100 105

<210> 664

<211> 12

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 664

Arg Ala Ser Gln Ser Val Ser Ser Ser Tyr Leu Ala

1 5 10

<210> 665

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 665

Gly Gln Ser Ser Arg Thr Arg

15

<210> 666

<211> 10

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 666

Gln Gln Phe Gly Asp Ser Arg Leu Phe Thr

1 5 10

<210> 667

<211> 120

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 667

Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Glu

1 5 10 15

Ser Leu Arg Ile Ser Cys Lys Gly Ser Gly Tyr Ser Phe Thr Thr Ser

20 25 30

Trp Ile Ser Trp Val Arg Gln Met Pro Gly Lys Gly Leu Glu Trp Met

35 40 45

Gly Met Ile Asp Pro Ser Asp Ser Phe Thr Ser Tyr Ser Pro Ser Phe

50 55 60

Gln Gly His Val Thr Ile Ser Ala Asp Lys Ser Ile Ser Thr Ala Tyr

65 70 75 80

Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala Met Tyr Tyr Cys

85 90 95

Ala Arg Leu His Tyr Tyr His Ser Glu Glu Phe Asp Val Trp Gly Gln

100 105 110

Gly Thr Met Val Thr Val Ser Ser

115 120

<210> 668

<211> 5

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 668

Thr Ser Trp Ile Ser

15

<210> 669

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 669

Met Ile Asp Pro Ser Asp Ser Phe Thr Ser Tyr Ser Pro Ser Phe Gln

1 5 10 15

Gly

<210> 670

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 670

Leu His Tyr Tyr His Ser Glu Glu Phe Asp Val

1 5 10

<210> 671

<211> 109

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 671

Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly

1 5 10 15

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Ser

20 25 30

Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu

35 40 45

Ile Tyr Gly Gln Ser Ser Arg Thr Arg 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 Gln Gln Phe Gly Asp Ser Arg

85 90 95

Leu Phe Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

100 105

<210> 672

<211> 12

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 672

Arg Ala Ser Gln Ser Val Ser Ser Ser Tyr Leu Ala

1 5 10

<210> 673

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 673

Gly Gln Ser Ser Arg Thr Arg

15

<210> 674

<211> 10

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 674

Gln Gln Phe Gly Asp Ser Arg Leu Phe Thr

1 5 10

<210> 675

<211> 120

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 675

Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Glu

1 5 10 15

Ser Leu Arg Ile Ser Cys Lys Gly Ser Gly Tyr Ser Phe Thr Thr Ser

20 25 30

Trp Ile Ser Trp Val Arg Gln Met Pro Gly Lys Gly Leu Glu Trp Met

35 40 45

Gly Met Ile Asp Pro Ser Asp Ser Tyr Thr Ser Tyr Ser Pro Ser Phe

50 55 60

Gln Gly His Val Thr Ile Ser Ala Asp Lys Ser Ile Ser Thr Ala Tyr

65 70 75 80

Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala Met Tyr Tyr Cys

85 90 95

Ala Arg Leu His Tyr Tyr His Ser Glu Glu Phe Asp Val Trp Gly Gln

100 105 110

Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 676

<211> 5

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 676

Thr Ser Trp Ile Ser

15

<210> 677

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 677

Met Ile Asp Pro Ser Asp Ser Tyr Thr Ser Tyr Ser Pro Ser Phe Gln

1 5 10 15

Gly

<210> 678

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 678

Leu His Tyr Tyr His Ser Glu Glu Phe Asp Val

1 5 10

<210> 679

<211> 109

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 679

Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly

1 5 10 15

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Ser

20 25 30

Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu

35 40 45

Ile Tyr Gly Gln Ser Ser Arg Thr Arg 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 Gln Gln Phe Gly Asp Ser Arg

85 90 95

Leu Phe Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

100 105

<210> 680

<211> 12

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 680

Arg Ala Ser Gln Ser Val Ser Ser Ser Tyr Leu Ala

1 5 10

<210> 681

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 681

Gly Gln Ser Ser Arg Thr Arg

15

<210> 682

<211> 10

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 682

Gln Gln Phe Gly Asp Ser Arg Leu Phe Thr

1 5 10

<210> 683

<211> 120

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 683

Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Glu

1 5 10 15

Ser Leu Arg Ile Ser Cys Lys Gly Ser Gly Tyr Ser Phe Thr Thr Ser

20 25 30

Trp Ile Ser Trp Val Arg Gln Met Pro Gly Lys Gly Leu Glu Trp Met

35 40 45

Gly Met Ile Asp Pro Ser Asp Ser Tyr Thr Ser Tyr Ser Pro Ser Phe

50 55 60

Gln Gly His Val Thr Ile Ser Ala Asp Lys Ser Ile Ser Thr Ala Tyr

65 70 75 80

Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala Met Tyr Tyr Cys

85 90 95

Ala Arg Leu His Tyr Tyr His Ser Glu Glu Phe Asp Val Trp Gly Gln

100 105 110

Gly Thr Met Val Thr Val Ser Ser

115 120

<210> 684

<211> 5

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 684

Thr Ser Trp Ile Ser

15

<210> 685

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 685

Met Ile Asp Pro Ser Asp Ser Tyr Thr Ser Tyr Ser Pro Ser Phe Gln

1 5 10 15

Gly

<210> 686

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 686

Leu His Tyr Tyr His Ser Glu Glu Phe Asp Val

1 5 10

<210> 687

<211> 109

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 687

Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly

1 5 10 15

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Ser

20 25 30

Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu

35 40 45

Ile Tyr Gly Gln Ser Ser Arg Thr Arg 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 Gln Gln Phe Gly Asp Ser Arg

85 90 95

Leu Phe Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

100 105

<210> 688

<211> 12

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 688

Arg Ala Ser Gln Ser Val Ser Ser Ser Tyr Leu Ala

1 5 10

<210> 689

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 689

Gly Gln Ser Ser Arg Thr Arg

15

<210> 690

<211> 10

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 690

Gln Gln Phe Gly Asp Ser Arg Leu Phe Thr

1 5 10

<210> 691

<211> 120

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 691

Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Glu

1 5 10 15

Ser Leu Arg Ile Ser Cys Lys Gly Ser Gly Tyr Ser Phe Ser Thr Ser

20 25 30

Trp Ile Ser Trp Val Arg Gln Met Pro Gly Lys Gly Leu Glu Trp Met

35 40 45

Gly Met Ile Asp Pro Ser Asp Ser Phe Thr Ser Tyr Ser Pro Ser Phe

50 55 60

Gln Gly His Val Thr Ile Ser Ala Asp Lys Ser Ile Ser Thr Ala Tyr

65 70 75 80

Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala Met Tyr Tyr Cys

85 90 95

Ala Arg Leu His Tyr Tyr Asn Ser Glu Glu Phe Asp Val Trp Gly Gln

100 105 110

Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 692

<211> 5

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 692

Thr Ser Trp Ile Ser

15

<210> 693

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 693

Met Ile Asp Pro Ser Asp Ser Phe Thr Ser Tyr Ser Pro Ser Phe Gln

1 5 10 15

Gly

<210> 694

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 694

Leu His Tyr Tyr Asn Ser Glu Glu Phe Asp Val

1 5 10

<210> 695

<211> 109

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 695

Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly

1 5 10 15

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Ser

20 25 30

Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu

35 40 45

Ile Tyr Gly Gln Ser Ser Arg Thr Arg 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 Gln Gln Phe Gly Asp Ser Arg

85 90 95

Leu Phe Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

100 105

<210> 696

<211> 12

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 696

Arg Ala Ser Gln Ser Val Ser Ser Ser Tyr Leu Ala

1 5 10

<210> 697

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 697

Gly Gln Ser Ser Arg Thr Arg

15

<210> 698

<211> 10

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

400>698

Gln Gln Phe Gly Asp Ser Arg Leu Phe Thr

1 5 10

<210> 699

<211> 120

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 699

Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Glu

1 5 10 15

Ser Leu Arg Ile Ser Cys Lys Gly Ser Gly Tyr Ser Phe Ser Thr Ser

20 25 30

Trp Ile Val Trp Val Arg Gln Met Pro Gly Lys Gly Leu Glu Trp Met

35 40 45

Gly Met Ile Asp Pro Ser Asp Ser Tyr Thr Ser Tyr Ser Pro Ser Phe

50 55 60

Gln Gly His Val Thr Ile Ser Ala Asp Lys Ser Ile Ser Thr Ala Tyr

65 70 75 80

Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala Met Tyr Tyr Cys

85 90 95

Ala Arg Leu His Tyr Tyr Asn Ser Glu Glu Phe Asp Val Trp Gly Gln

100 105 110

Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 700

<211> 5

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 700

Thr Ser Trp Ile Val

15

<210> 701

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 701

Met Ile Asp Pro Ser Asp Ser Tyr Thr Ser Tyr Ser Pro Ser Phe Gln

1 5 10 15

Gly

<210> 702

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 702

Leu His Tyr Tyr Asn Ser Glu Glu Phe Asp Val

1 5 10

<210> 703

<211> 109

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 703

Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly

1 5 10 15

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Ser

20 25 30

Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu

35 40 45

Ile Tyr Gly Gln Ser Ser Arg Thr Arg 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 Gln Gln Phe Gly Asp Ser Arg

85 90 95

Leu Phe Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

100 105

<210> 704

<211> 12

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 704

Arg Ala Ser Gln Ser Val Ser Ser Ser Tyr Leu Ala

1 5 10

<210> 705

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 705

Gly Gln Ser Ser Arg Thr Arg

15

<210> 706

<211> 10

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 706

Gln Gln Phe Gly Asp Ser Arg Leu Phe Thr

1 5 10

<210> 707

<211> 120

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 707

Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Glu

1 5 10 15

Ser Leu Arg Ile Ser Cys Lys Gly Ser Gly Tyr Ser Phe Ser Thr Ser

20 25 30

Trp Ile Val Trp Val Arg Gln Met Pro Gly Lys Gly Leu Glu Trp Met

35 40 45

Gly Met Ile Asp Pro Ser Asp Ser Phe Thr Ser Tyr Ser Pro Ser Phe

50 55 60

Gln Gly His Val Thr Ile Ser Ala Asp Lys Ser Ile Ser Thr Ala Tyr

65 70 75 80

Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala Met Tyr Tyr Cys

85 90 95

Ala Arg Leu His Tyr Tyr Asn Ser Glu Glu Phe Asp Val Trp Gly Gln

100 105 110

Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 708

<211> 5

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 708

Thr Ser Trp Ile Val

15

<210> 709

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 709

Met Ile Asp Pro Ser Asp Ser Phe Thr Ser Tyr Ser Pro Ser Phe Gln

1 5 10 15

Gly

<210> 710

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 710

Leu His Tyr Tyr Asn Ser Glu Glu Phe Asp Val

1 5 10

<210> 711

<211> 109

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 711

Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly

1 5 10 15

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Ser

20 25 30

Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu

35 40 45

Ile Tyr Gly Gln Ser Ser Arg Thr Arg 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 Gln Gln Phe Gly Ser Ser Gln

85 90 95

Leu Phe Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

100 105

<210> 712

<211> 12

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 712

Arg Ala Ser Gln Ser Val Ser Ser Ser Tyr Leu Ala

1 5 10

<210> 713

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 713

Gly Gln Ser Ser Arg Thr Arg

15

<210> 714

<211> 10

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 714

Gln Gln Phe Gly Ser Ser Gln Leu Phe Thr

1 5 10

<210> 715

<211> 120

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 715

Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Glu

1 5 10 15

Ser Leu Arg Ile Ser Cys Lys Gly Ser Gly Tyr Ser Phe Ser Thr Ser

20 25 30

Trp Ile Val Trp Val Arg Gln Met Pro Gly Lys Gly Leu Glu Trp Met

35 40 45

Gly Met Ile Asp Pro Ser Asp Ser Phe Thr Ser Tyr Ser Pro Ser Phe

50 55 60

Gln Gly His Val Thr Ile Ser Ala Asp Lys Ser Ile Ser Thr Ala Tyr

65 70 75 80

Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala Met Tyr Tyr Cys

85 90 95

Ala Arg Leu His Tyr Tyr Asn Ser Glu Glu Phe Asp Val Trp Gly Gln

100 105 110

Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 716

<211> 5

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 716

Thr Ser Trp Ile Val

15

<210> 717

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 717

Met Ile Asp Pro Ser Asp Ser Phe Thr Ser Tyr Ser Pro Ser Phe Gln

1 5 10 15

Gly

<210> 718

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 718

Leu His Tyr Tyr Asn Ser Glu Glu Phe Asp Val

1 5 10

<210> 719

<211> 109

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 719

Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly

1 5 10 15

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Ser

20 25 30

Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu

35 40 45

Ile Tyr Gly Gln Ser Ser Arg Thr Arg 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 Gln Gln Phe Gly Glu Ser Gln

85 90 95

Leu Phe Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

100 105

<210> 720

<211> 12

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 720

Arg Ala Ser Gln Ser Val Ser Ser Ser Tyr Leu Ala

1 5 10

<210> 721

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 721

Gly Gln Ser Ser Arg Thr Arg

15

<210> 722

<211> 10

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 722

Gln Gln Phe Gly Glu Ser Gln Leu Phe Thr

1 5 10

<210> 723

<211> 120

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 723

Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Glu

1 5 10 15

Ser Leu Arg Ile Ser Cys Lys Gly Ser Gly Tyr Ser Phe Ser Thr Ser

20 25 30

Trp Ile Val Trp Val Arg Gln Met Pro Gly Lys Gly Leu Glu Trp Met

35 40 45

Gly Met Ile Asp Pro Ser Asp Ser Phe Thr Ser Tyr Ser Pro Ser Phe

50 55 60

Gln Gly His Val Thr Ile Ser Ala Asp Lys Ser Ile Ser Thr Ala Tyr

65 70 75 80

Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala Met Tyr Tyr Cys

85 90 95

Ala Arg Leu His Tyr Tyr Asn Ser Glu Glu Phe Asp Val Trp Gly Gln

100 105 110

Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 724

<211> 5

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 724

Thr Ser Trp Ile Val

15

<210> 725

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 725

Met Ile Asp Pro Ser Asp Ser Phe Thr Ser Tyr Ser Pro Ser Phe Gln

1 5 10 15

Gly

<210> 726

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 726

Leu His Tyr Tyr Asn Ser Glu Glu Phe Asp Val

1 5 10

<210> 727

<211> 109

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 727

Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly

1 5 10 15

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Ser

20 25 30

Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu

35 40 45

Ile Tyr Gly Gln Ser Ser Arg Thr Arg 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 Gln Gln Phe Gly Asn Ser Gln

85 90 95

Leu Phe Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

100 105

<210> 728

<211> 12

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 728

Arg Ala Ser Gln Ser Val Ser Ser Ser Tyr Leu Ala

1 5 10

<210> 729

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 729

Gly Gln Ser Ser Arg Thr Arg

15

<210> 730

<211> 10

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 730

Gln Gln Phe Gly Asn Ser Gln Leu Phe Thr

1 5 10

<210> 731

<211> 120

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 731

Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Glu

1 5 10 15

Ser Leu Arg Ile Ser Cys Lys Gly Ser Gly Tyr Ser Phe Ser Thr Ser

20 25 30

Trp Ile Val Trp Val Arg Gln Met Pro Gly Lys Gly Leu Glu Trp Met

35 40 45

Gly Met Ile Asp Pro Ser Asp Ser Phe Thr Ser Tyr Ser Pro Ser Phe

50 55 60

Gln Gly His Val Thr Ile Ser Ala Asp Lys Ser Ile Ser Thr Ala Tyr

65 70 75 80

Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala Met Tyr Tyr Cys

85 90 95

Ala Arg Leu His Tyr Tyr Asn Ser Glu Glu Phe Asp Val Trp Gly Gln

100 105 110

Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 732

<211> 5

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 732

Thr Ser Trp Ile Val

15

<210> 733

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 733

Met Ile Asp Pro Ser Asp Ser Phe Thr Ser Tyr Ser Pro Ser Phe Gln

1 5 10 15

Gly

<210> 734

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 734

Leu His Tyr Tyr Asn Ser Glu Glu Phe Asp Val

1 5 10

<210> 735

<211> 109

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 735

Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly

1 5 10 15

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Ser

20 25 30

Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu

35 40 45

Ile Tyr Gly Gln Ser Ser Arg Thr Arg 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 Gln Gln Phe Gly Gln Ser Gln

85 90 95

Leu Phe Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

100 105

<210> 736

<211> 12

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 736

Arg Ala Ser Gln Ser Val Ser Ser Ser Tyr Leu Ala

1 5 10

<210> 737

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 737

Gly Gln Ser Ser Arg Thr Arg

15

<210> 738

<211> 10

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 738

Gln Gln Phe Gly Gln Ser Gln Leu Phe Thr

1 5 10

<210> 739

<211> 120

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 739

Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Glu

1 5 10 15

Ser Leu Arg Ile Ser Cys Lys Gly Ser Gly Tyr Ser Phe Ser Thr Ser

20 25 30

Trp Ile Val Trp Val Arg Gln Met Pro Gly Lys Gly Leu Glu Trp Met

35 40 45

Gly Met Ile Asp Pro Ser Asp Ser Phe Thr Ser Tyr Ser Pro Ser Phe

50 55 60

Gln Gly His Val Thr Ile Ser Ala Asp Lys Ser Ile Ser Thr Ala Tyr

65 70 75 80

Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala Met Tyr Tyr Cys

85 90 95

Ala Arg Leu His Tyr Tyr Asn Ser Glu Glu Phe Asp Val Trp Gly Gln

100 105 110

Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 740

<211> 5

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 740

Thr Ser Trp Ile Val

15

<210> 741

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 741

Met Ile Asp Pro Ser Asp Ser Phe Thr Ser Tyr Ser Pro Ser Phe Gln

1 5 10 15

Gly

<210> 742

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 742

Leu His Tyr Tyr Asn Ser Glu Glu Phe Asp Val

1 5 10

<210> 743

<211> 109

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 743

Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly

1 5 10 15

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Ser

20 25 30

Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu

35 40 45

Ile Tyr Gly Gln Ser Ser Arg Thr Arg 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 Gln Gln Phe Gly Asp Ala Gln

85 90 95

Leu Phe Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

100 105

<210> 744

<211> 12

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 744

Arg Ala Ser Gln Ser Val Ser Ser Ser Tyr Leu Ala

1 5 10

<210> 745

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 745

Gly Gln Ser Ser Arg Thr Arg

15

<210> 746

<211> 10

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 746

Gln Gln Phe Gly Asp Ala Gln Leu Phe Thr

1 5 10

<210> 747

<211> 120

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 747

Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Glu

1 5 10 15

Ser Leu Arg Ile Ser Cys Lys Gly Ser Gly Tyr Ser Phe Ser Thr Ser

20 25 30

Trp Ile Val Trp Val Arg Gln Met Pro Gly Lys Gly Leu Glu Trp Met

35 40 45

Gly Met Ile Asp Pro Ser Asp Ser Phe Thr Ser Tyr Ser Pro Ser Phe

50 55 60

Gln Gly His Val Thr Ile Ser Ala Asp Lys Ser Ile Ser Thr Ala Tyr

65 70 75 80

Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala Met Tyr Tyr Cys

85 90 95

Ala Arg Leu His Tyr Tyr Asn Ser Glu Glu Phe Asp Val Trp Gly Gln

100 105 110

Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 748

<211> 5

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 748

Thr Ser Trp Ile Val

15

<210> 749

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 749

Met Ile Asp Pro Ser Asp Ser Phe Thr Ser Tyr Ser Pro Ser Phe Gln

1 5 10 15

Gly

<210> 750

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 750

Leu His Tyr Tyr Asn Ser Glu Glu Phe Asp Val

1 5 10

<210> 751

<211> 109

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 751

Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly

1 5 10 15

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Ser

20 25 30

Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu

35 40 45

Ile Tyr Gly Gln Ser Ser Arg Thr Arg 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 Gln Gln Phe Gly Asp Thr Gln

85 90 95

Leu Phe Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

100 105

<210> 752

<211> 12

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 752

Arg Ala Ser Gln Ser Val Ser Ser Ser Tyr Leu Ala

1 5 10

<210> 753

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 753

Gly Gln Ser Ser Arg Thr Arg

15

<210> 754

<211> 10

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 754

Gln Gln Phe Gly Asp Thr Gln Leu Phe Thr

1 5 10

<210> 755

<211> 120

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 755

Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Glu

1 5 10 15

Ser Leu Arg Ile Ser Cys Lys Gly Ser Gly Tyr Ser Phe Ser Thr Ser

20 25 30

Trp Ile Val Trp Val Arg Gln Met Pro Gly Lys Gly Leu Glu Trp Met

35 40 45

Gly Met Ile Asp Pro Ser Asp Ser Phe Thr Ser Tyr Ser Pro Ser Phe

50 55 60

Gln Gly His Val Thr Ile Ser Ala Asp Lys Ser Ile Ser Thr Ala Tyr

65 70 75 80

Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala Met Tyr Tyr Cys

85 90 95

Ala Arg Leu His Tyr Tyr Asn Ser Glu Glu Phe Asp Val Trp Gly Gln

100 105 110

Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 756

<211> 5

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 756

Thr Ser Trp Ile Val

15

<210> 757

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 757

Met Ile Asp Pro Ser Asp Ser Phe Thr Ser Tyr Ser Pro Ser Phe Gln

1 5 10 15

Gly

<210> 758

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 758

Leu His Tyr Tyr Asn Ser Glu Glu Phe Asp Val

1 5 10

<210> 759

<211> 109

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 759

Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly

1 5 10 15

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Ser

20 25 30

Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu

35 40 45

Ile Tyr Gly Gln Ser Ser Arg Thr Arg 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 Gln Gln Phe Gly Asp Asn Gln

85 90 95

Leu Phe Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

100 105

<210> 760

<211> 12

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 760

Arg Ala Ser Gln Ser Val Ser Ser Ser Tyr Leu Ala

1 5 10

<210> 761

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 761

Gly Gln Ser Ser Arg Thr Arg

15

<210> 762

<211> 10

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 762

Gln Gln Phe Gly Asp Asn Gln Leu Phe Thr

1 5 10

<210> 763

<211> 120

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 763

Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Glu

1 5 10 15

Ser Leu Arg Ile Ser Cys Lys Gly Ser Gly Tyr Ser Phe Ser Thr Ser

20 25 30

Trp Ile Ser Trp Val Arg Gln Met Pro Gly Lys Gly Leu Glu Trp Met

35 40 45

Gly Met Ile Asp Pro Ser Asp Ser Tyr Thr Ser Tyr Ser Pro Ser Phe

50 55 60

Gln Gly His Val Thr Ile Ser Ala Asp Lys Ser Ile Ser Thr Ala Tyr

65 70 75 80

Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala Met Tyr Tyr Cys

85 90 95

Ala Arg Leu His Tyr Tyr Asn Ser Glu Glu Phe Asp Val Trp Gly Gln

100 105 110

Gly Thr Met Val Thr Val Ser Ser

115 120

<210> 764

<211> 5

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 764

Thr Ser Trp Ile Ser

15

<210> 765

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 765

Met Ile Asp Pro Ser Asp Ser Tyr Thr Ser Tyr Ser Pro Ser Phe Gln

1 5 10 15

Gly

<210> 766

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 766

Leu His Tyr Tyr Asn Ser Glu Glu Phe Asp Val

1 5 10

<210> 767

<211> 109

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 767

Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly

1 5 10 15

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Ser

20 25 30

Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu

35 40 45

Ile Tyr Gly Gln Ser Ser Arg Thr Arg 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 Gln Gln Phe Gly Ser Ser Gln

85 90 95

Leu Phe Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

100 105

<210> 768

<211> 12

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 768

Arg Ala Ser Gln Ser Val Ser Ser Ser Tyr Leu Ala

1 5 10

<210> 769

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 769

Gly Gln Ser Ser Arg Thr Arg

15

<210> 770

<211> 10

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 770

Gln Gln Phe Gly Ser Ser Gln Leu Phe Thr

1 5 10

<210> 771

<211> 120

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 771

Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Glu

1 5 10 15

Ser Leu Arg Ile Ser Cys Lys Gly Ser Gly Tyr Ser Phe Thr Thr Ser

20 25 30

Trp Ile Ser Trp Val Arg Gln Met Pro Gly Lys Gly Leu Glu Trp Met

35 40 45

Gly Met Ile Asp Pro Ser Asp Ser Phe Thr Ser Tyr Ser Pro Ser Phe

50 55 60

Gln Gly His Val Thr Ile Ser Ala Asp Lys Ser Ile Ser Thr Ala Tyr

65 70 75 80

Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala Met Tyr Tyr Cys

85 90 95

Ala Arg Leu His Tyr Tyr His Ser Glu Glu Phe Asp Val Trp Gly Gln

100 105 110

Gly Thr Met Val Thr Val Ser Ser

115 120

<210> 772

<211> 5

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 772

Thr Ser Trp Ile Ser

15

<210> 773

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 773

Met Ile Asp Pro Ser Asp Ser Phe Thr Ser Tyr Ser Pro Ser Phe Gln

1 5 10 15

Gly

<210> 774

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 774

Leu His Tyr Tyr His Ser Glu Glu Phe Asp Val

1 5 10

<210> 775

<211> 109

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 775

Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly

1 5 10 15

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Ser

20 25 30

Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu

35 40 45

Ile Tyr Gly Gln Ser Ser Arg Thr Arg 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 Gln Gln Phe Gly Ser Ser Gln

85 90 95

Leu Phe Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

100 105

<210> 776

<211> 12

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 776

Arg Ala Ser Gln Ser Val Ser Ser Ser Tyr Leu Ala

1 5 10

<210> 777

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 777

Gly Gln Ser Ser Arg Thr Arg

15

<210> 778

<211> 10

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 778

Gln Gln Phe Gly Ser Ser Gln Leu Phe Thr

1 5 10

<210> 779

<211> 120

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 779

Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Glu

1 5 10 15

Ser Leu Arg Ile Ser Cys Lys Gly Ser Gly Tyr Ser Phe Thr Thr Ser

20 25 30

Trp Ile Ser Trp Val Arg Gln Met Pro Gly Lys Gly Leu Glu Trp Met

35 40 45

Gly Met Ile Asp Pro Ser Asp Ser Tyr Thr Ser Tyr Ser Pro Ser Phe

50 55 60

Gln Gly His Val Thr Ile Ser Ala Asp Lys Ser Ile Ser Thr Ala Tyr

65 70 75 80

Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala Met Tyr Tyr Cys

85 90 95

Ala Arg Leu His Tyr Tyr His Ser Glu Glu Phe Asp Val Trp Gly Gln

100 105 110

Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 780

<211> 5

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 780

Thr Ser Trp Ile Ser

15

<210> 781

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 781

Met Ile Asp Pro Ser Asp Ser Tyr Thr Ser Tyr Ser Pro Ser Phe Gln

1 5 10 15

Gly

<210> 782

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 782

Leu His Tyr Tyr His Ser Glu Glu Phe Asp Val

1 5 10

<210> 783

<211> 109

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 783

Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly

1 5 10 15

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Ser

20 25 30

Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu

35 40 45

Ile Tyr Gly Gln Ser Ser Arg Thr Arg 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 Gln Gln Phe Gly Ser Ser Gln

85 90 95

Leu Phe Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

100 105

<210> 784

<211> 12

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 784

Arg Ala Ser Gln Ser Val Ser Ser Ser Tyr Leu Ala

1 5 10

<210> 785

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 785

Gly Gln Ser Ser Arg Thr Arg

15

<210> 786

<211> 10

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 786

Gln Gln Phe Gly Ser Ser Gln Leu Phe Thr

1 5 10

<210> 787

<211> 120

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 787

Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Glu

1 5 10 15

Ser Leu Arg Ile Ser Cys Lys Gly Ser Gly Tyr Ser Phe Thr Thr Ser

20 25 30

Trp Ile Ser Trp Val Arg Gln Met Pro Gly Lys Gly Leu Glu Trp Met

35 40 45

Gly Met Ile Asp Pro Ser Asp Ser Tyr Thr Ser Tyr Ser Pro Ser Phe

50 55 60

Gln Gly His Val Thr Ile Ser Ala Asp Lys Ser Ile Ser Thr Ala Tyr

65 70 75 80

Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala Met Tyr Tyr Cys

85 90 95

Ala Arg Leu His Tyr Tyr His Ser Glu Glu Phe Asp Val Trp Gly Gln

100 105 110

Gly Thr Met Val Thr Val Ser Ser

115 120

<210> 788

<211> 5

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 788

Thr Ser Trp Ile Ser

15

<210> 789

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 789

Met Ile Asp Pro Ser Asp Ser Tyr Thr Ser Tyr Ser Pro Ser Phe Gln

1 5 10 15

Gly

<210> 790

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 790

Leu His Tyr Tyr His Ser Glu Glu Phe Asp Val

1 5 10

<210> 791

<211> 109

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 791

Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly

1 5 10 15

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Ser

20 25 30

Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu

35 40 45

Ile Tyr Gly Gln Ser Ser Arg Thr Arg 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 Gln Gln Phe Gly Ser Ser Gln

85 90 95

Leu Phe Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

100 105

<210> 792

<211> 12

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 792

Arg Ala Ser Gln Ser Val Ser Ser Ser Tyr Leu Ala

1 5 10

<210> 793

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 793

Gly Gln Ser Ser Arg Thr Arg

15

<210> 794

<211> 10

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 794

Gln Gln Phe Gly Ser Ser Gln Leu Phe Thr

1 5 10

<210> 795

<211> 120

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 795

Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Glu

1 5 10 15

Ser Leu Arg Ile Ser Cys Lys Gly Ser Gly Tyr Ser Phe Ser Thr Ser

20 25 30

Trp Ile Ser Trp Val Arg Gln Met Pro Gly Lys Gly Leu Glu Trp Met

35 40 45

Gly Met Ile Asp Pro Ser Asp Ser Phe Thr Ser Tyr Ser Pro Ser Phe

50 55 60

Gln Gly His Val Thr Ile Ser Ala Asp Lys Ser Ile Ser Thr Ala Tyr

65 70 75 80

Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala Met Tyr Tyr Cys

85 90 95

Ala Arg Leu His Tyr Tyr Asn Ser Glu Glu Phe Asp Val Trp Gly Gln

100 105 110

Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 796

<211> 5

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 796

Thr Ser Trp Ile Ser

15

<210> 797

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 797

Met Ile Asp Pro Ser Asp Ser Phe Thr Ser Tyr Ser Pro Ser Phe Gln

1 5 10 15

Gly

<210> 798

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 798

Leu His Tyr Tyr Asn Ser Glu Glu Phe Asp Val

1 5 10

<210> 799

<211> 109

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 799

Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly

1 5 10 15

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Ser

20 25 30

Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu

35 40 45

Ile Tyr Gly Gln Ser Ser Arg Thr Arg 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 Gln Gln Phe Gly Ser Ser Gln

85 90 95

Leu Phe Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

100 105

<210> 800

<211> 12

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 800

Arg Ala Ser Gln Ser Val Ser Ser Ser Tyr Leu Ala

1 5 10

<210> 801

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 801

Gly Gln Ser Ser Arg Thr Arg

15

<210> 802

<211> 10

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 802

Gln Gln Phe Gly Ser Ser Gln Leu Phe Thr

1 5 10

<210> 803

<211> 120

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 803

Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Glu

1 5 10 15

Ser Leu Arg Ile Ser Cys Lys Gly Ser Gly Tyr Ser Phe Ser Thr Ser

20 25 30

Trp Ile Val Trp Val Arg Gln Met Pro Gly Lys Gly Leu Glu Trp Met

35 40 45

Gly Met Ile Asp Pro Ser Asp Ser Tyr Thr Ser Tyr Ser Pro Ser Phe

50 55 60

Gln Gly His Val Thr Ile Ser Ala Asp Lys Ser Ile Ser Thr Ala Tyr

65 70 75 80

Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala Met Tyr Tyr Cys

85 90 95

Ala Arg Leu His Tyr Tyr Asn Ser Glu Glu Phe Asp Val Trp Gly Gln

100 105 110

Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 804

<211> 5

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 804

Thr Ser Trp Ile Val

15

<210> 805

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 805

Met Ile Asp Pro Ser Asp Ser Tyr Thr Ser Tyr Ser Pro Ser Phe Gln

1 5 10 15

Gly

<210> 806

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 806

Leu His Tyr Tyr Asn Ser Glu Glu Phe Asp Val

1 5 10

<210> 807

<211> 109

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 807

Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly

1 5 10 15

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Ser

20 25 30

Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu

35 40 45

Ile Tyr Gly Gln Ser Ser Arg Thr Arg 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 Gln Gln Phe Gly Ser Ser Gln

85 90 95

Leu Phe Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

100 105

<210> 808

<211> 12

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 808

Arg Ala Ser Gln Ser Val Ser Ser Ser Tyr Leu Ala

1 5 10

<210> 809

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 809

Gly Gln Ser Ser Arg Thr Arg

15

<210> 810

<211> 10

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 810

Gln Gln Phe Gly Ser Ser Gln Leu Phe Thr

1 5 10

<210> 811

<211> 120

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 811

Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Glu

1 5 10 15

Ser Leu Arg Ile Ser Cys Lys Gly Ser Gly Tyr Ser Phe Ser Thr Ser

20 25 30

Trp Ile Val Trp Val Arg Gln Met Pro Gly Lys Gly Leu Glu Trp Met

35 40 45

Gly Met Ile Asp Pro Ser Asp Ser Tyr Thr Ser Tyr Ser Pro Ser Phe

50 55 60

Gln Gly His Val Thr Ile Ser Ala Asp Lys Ser Ile Ser Thr Ala Tyr

65 70 75 80

Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala Met Tyr Tyr Cys

85 90 95

Ala Arg Leu His Tyr Tyr Asn Ser Glu Glu Phe Asp Val Trp Gly Gln

100 105 110

Gly Thr Met Val Thr Val Ser Ser

115 120

<210> 812

<211> 5

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 812

Thr Ser Trp Ile Val

15

<210> 813

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 813

Met Ile Asp Pro Ser Asp Ser Tyr Thr Ser Tyr Ser Pro Ser Phe Gln

1 5 10 15

Gly

<210> 814

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 814

Leu His Tyr Tyr Asn Ser Glu Glu Phe Asp Val

1 5 10

<210> 815

<211> 109

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 815

Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly

1 5 10 15

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Ser

20 25 30

Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu

35 40 45

Ile Tyr Gly Gln Ser Ser Arg Thr Arg 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 Gln Gln Phe Gly Ser Ser Gln

85 90 95

Leu Phe Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

100 105

<210> 816

<211> 12

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 816

Arg Ala Ser Gln Ser Val Ser Ser Ser Tyr Leu Ala

1 5 10

<210> 817

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 817

Gly Gln Ser Ser Arg Thr Arg

15

<210> 818

<211> 10

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 818

Gln Gln Phe Gly Ser Ser Gln Leu Phe Thr

1 5 10

<210> 819

<211> 120

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 819

Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Glu

1 5 10 15

Ser Leu Arg Ile Ser Cys Lys Gly Ser Gly Tyr Ser Phe Ser Thr Ser

20 25 30

Trp Ile Ser Trp Val Arg Gln Met Pro Gly Lys Gly Leu Glu Trp Met

35 40 45

Gly Met Ile Asp Pro Ser Asp Ser Tyr Thr Ser Tyr Ser Pro Ser Phe

50 55 60

Gln Gly His Val Thr Ile Ser Ala Asp Lys Ser Ile Ser Thr Ala Tyr

65 70 75 80

Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala Met Tyr Tyr Cys

85 90 95

Ala Arg Leu His Tyr Tyr Asn Ser Glu Glu Phe Asp Val Trp Gly Gln

100 105 110

Gly Thr Met Val Thr Val Ser Ser

115 120

<210> 820

<211> 5

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 820

Thr Ser Trp Ile Ser

15

<210> 821

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 821

Met Ile Asp Pro Ser Asp Ser Tyr Thr Ser Tyr Ser Pro Ser Phe Gln

1 5 10 15

Gly

<210> 822

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 822

Leu His Tyr Tyr Asn Ser Glu Glu Phe Asp Val

1 5 10

<210> 823

<211> 109

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 823

Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly

1 5 10 15

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Ser

20 25 30

Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu

35 40 45

Ile Tyr Gly Gln Ser Ser Arg Thr Arg 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 Gln Gln Phe Gly Glu Ser Gln

85 90 95

Leu Phe Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

100 105

<210> 824

<211> 12

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 824

Arg Ala Ser Gln Ser Val Ser Ser Ser Tyr Leu Ala

1 5 10

<210> 825

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 825

Gly Gln Ser Ser Arg Thr Arg

15

<210> 826

<211> 10

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 826

Gln Gln Phe Gly Glu Ser Gln Leu Phe Thr

1 5 10

<210> 827

<211> 120

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 827

Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Glu

1 5 10 15

Ser Leu Arg Ile Ser Cys Lys Gly Ser Gly Tyr Ser Phe Thr Thr Ser

20 25 30

Trp Ile Ser Trp Val Arg Gln Met Pro Gly Lys Gly Leu Glu Trp Met

35 40 45

Gly Met Ile Asp Pro Ser Asp Ser Phe Thr Ser Tyr Ser Pro Ser Phe

50 55 60

Gln Gly His Val Thr Ile Ser Ala Asp Lys Ser Ile Ser Thr Ala Tyr

65 70 75 80

Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala Met Tyr Tyr Cys

85 90 95

Ala Arg Leu His Tyr Tyr His Ser Glu Glu Phe Asp Val Trp Gly Gln

100 105 110

Gly Thr Met Val Thr Val Ser Ser

115 120

<210> 828

<211> 5

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 828

Thr Ser Trp Ile Ser

15

<210> 829

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 829

Met Ile Asp Pro Ser Asp Ser Phe Thr Ser Tyr Ser Pro Ser Phe Gln

1 5 10 15

Gly

<210> 830

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 830

Leu His Tyr Tyr His Ser Glu Glu Phe Asp Val

1 5 10

<210> 831

<211> 109

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 831

Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly

1 5 10 15

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Ser

20 25 30

Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu

35 40 45

Ile Tyr Gly Gln Ser Ser Arg Thr Arg 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 Gln Gln Phe Gly Glu Ser Gln

85 90 95

Leu Phe Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

100 105

<210> 832

<211> 12

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 832

Arg Ala Ser Gln Ser Val Ser Ser Ser Tyr Leu Ala

1 5 10

<210> 833

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 833

Gly Gln Ser Ser Arg Thr Arg

15

<210> 834

<211> 10

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 834

Gln Gln Phe Gly Glu Ser Gln Leu Phe Thr

1 5 10

<210> 835

<211> 120

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 835

Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Glu

1 5 10 15

Ser Leu Arg Ile Ser Cys Lys Gly Ser Gly Tyr Ser Phe Thr Thr Ser

20 25 30

Trp Ile Ser Trp Val Arg Gln Met Pro Gly Lys Gly Leu Glu Trp Met

35 40 45

Gly Met Ile Asp Pro Ser Asp Ser Tyr Thr Ser Tyr Ser Pro Ser Phe

50 55 60

Gln Gly His Val Thr Ile Ser Ala Asp Lys Ser Ile Ser Thr Ala Tyr

65 70 75 80

Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala Met Tyr Tyr Cys

85 90 95

Ala Arg Leu His Tyr Tyr His Ser Glu Glu Phe Asp Val Trp Gly Gln

100 105 110

Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 836

<211> 5

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 836

Thr Ser Trp Ile Ser

15

<210> 837

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 837

Met Ile Asp Pro Ser Asp Ser Tyr Thr Ser Tyr Ser Pro Ser Phe Gln

1 5 10 15

Gly

<210> 838

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 838

Leu His Tyr Tyr His Ser Glu Glu Phe Asp Val

1 5 10

<210> 839

<211> 109

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 839

Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly

1 5 10 15

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Ser

20 25 30

Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu

35 40 45

Ile Tyr Gly Gln Ser Ser Arg Thr Arg 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 Gln Gln Phe Gly Glu Ser Gln

85 90 95

Leu Phe Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

100 105

<210> 840

<211> 12

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 840

Arg Ala Ser Gln Ser Val Ser Ser Ser Tyr Leu Ala

1 5 10

<210> 841

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 841

Gly Gln Ser Ser Arg Thr Arg

15

<210> 842

<211> 10

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 842

Gln Gln Phe Gly Glu Ser Gln Leu Phe Thr

1 5 10

<210> 843

<211> 120

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 843

Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Glu

1 5 10 15

Ser Leu Arg Ile Ser Cys Lys Gly Ser Gly Tyr Ser Phe Thr Thr Ser

20 25 30

Trp Ile Ser Trp Val Arg Gln Met Pro Gly Lys Gly Leu Glu Trp Met

35 40 45

Gly Met Ile Asp Pro Ser Asp Ser Tyr Thr Ser Tyr Ser Pro Ser Phe

50 55 60

Gln Gly His Val Thr Ile Ser Ala Asp Lys Ser Ile Ser Thr Ala Tyr

65 70 75 80

Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala Met Tyr Tyr Cys

85 90 95

Ala Arg Leu His Tyr Tyr His Ser Glu Glu Phe Asp Val Trp Gly Gln

100 105 110

Gly Thr Met Val Thr Val Ser Ser

115 120

<210> 844

<211> 5

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 844

Thr Ser Trp Ile Ser

15

<210> 845

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 845

Met Ile Asp Pro Ser Asp Ser Tyr Thr Ser Tyr Ser Pro Ser Phe Gln

1 5 10 15

Gly

<210> 846

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 846

Leu His Tyr Tyr His Ser Glu Glu Phe Asp Val

1 5 10

<210> 847

<211> 109

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 847

Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly

1 5 10 15

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Ser

20 25 30

Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu

35 40 45

Ile Tyr Gly Gln Ser Ser Arg Thr Arg 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 Gln Gln Phe Gly Glu Ser Gln

85 90 95

Leu Phe Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

100 105

<210> 848

<211> 12

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 848

Arg Ala Ser Gln Ser Val Ser Ser Ser Tyr Leu Ala

1 5 10

<210> 849

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 849

Gly Gln Ser Ser Arg Thr Arg

15

<210> 850

<211> 10

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 850

Gln Gln Phe Gly Glu Ser Gln Leu Phe Thr

1 5 10

<210> 851

<211> 120

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 851

Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Glu

1 5 10 15

Ser Leu Arg Ile Ser Cys Lys Gly Ser Gly Tyr Ser Phe Ser Thr Ser

20 25 30

Trp Ile Ser Trp Val Arg Gln Met Pro Gly Lys Gly Leu Glu Trp Met

35 40 45

Gly Met Ile Asp Pro Ser Asp Ser Phe Thr Ser Tyr Ser Pro Ser Phe

50 55 60

Gln Gly His Val Thr Ile Ser Ala Asp Lys Ser Ile Ser Thr Ala Tyr

65 70 75 80

Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala Met Tyr Tyr Cys

85 90 95

Ala Arg Leu His Tyr Tyr Asn Ser Glu Glu Phe Asp Val Trp Gly Gln

100 105 110

Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 852

<211> 5

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 852

Thr Ser Trp Ile Ser

15

<210> 853

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 853

Met Ile Asp Pro Ser Asp Ser Phe Thr Ser Tyr Ser Pro Ser Phe Gln

1 5 10 15

Gly

<210> 854

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 854

Leu His Tyr Tyr Asn Ser Glu Glu Phe Asp Val

1 5 10

<210> 855

<211> 109

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 855

Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly

1 5 10 15

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Ser

20 25 30

Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu

35 40 45

Ile Tyr Gly Gln Ser Ser Arg Thr Arg 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 Gln Gln Phe Gly Glu Ser Gln

85 90 95

Leu Phe Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

100 105

<210> 856

<211> 12

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 856

Arg Ala Ser Gln Ser Val Ser Ser Ser Tyr Leu Ala

1 5 10

<210> 857

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 857

Gly Gln Ser Ser Arg Thr Arg

15

<210> 858

<211> 10

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 858

Gln Gln Phe Gly Glu Ser Gln Leu Phe Thr

1 5 10

<210> 859

<211> 120

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 859

Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Glu

1 5 10 15

Ser Leu Arg Ile Ser Cys Lys Gly Ser Gly Tyr Ser Phe Ser Thr Ser

20 25 30

Trp Ile Val Trp Val Arg Gln Met Pro Gly Lys Gly Leu Glu Trp Met

35 40 45

Gly Met Ile Asp Pro Ser Asp Ser Tyr Thr Ser Tyr Ser Pro Ser Phe

50 55 60

Gln Gly His Val Thr Ile Ser Ala Asp Lys Ser Ile Ser Thr Ala Tyr

65 70 75 80

Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala Met Tyr Tyr Cys

85 90 95

Ala Arg Leu His Tyr Tyr Asn Ser Glu Glu Phe Asp Val Trp Gly Gln

100 105 110

Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 860

<211> 5

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 860

Thr Ser Trp Ile Val

15

<210> 861

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 861

Met Ile Asp Pro Ser Asp Ser Tyr Thr Ser Tyr Ser Pro Ser Phe Gln

1 5 10 15

Gly

<210> 862

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 862

Leu His Tyr Tyr Asn Ser Glu Glu Phe Asp Val

1 5 10

<210> 863

<211> 109

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 863

Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly

1 5 10 15

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Ser

20 25 30

Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu

35 40 45

Ile Tyr Gly Gln Ser Ser Arg Thr Arg 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 Gln Gln Phe Gly Glu Ser Gln

85 90 95

Leu Phe Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

100 105

<210> 864

<211> 12

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 864

Arg Ala Ser Gln Ser Val Ser Ser Ser Tyr Leu Ala

1 5 10

<210> 865

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 865

Gly Gln Ser Ser Arg Thr Arg

15

<210> 866

<211> 10

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 866

Gln Gln Phe Gly Glu Ser Gln Leu Phe Thr

1 5 10

<210> 867

<211> 120

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 867

Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Glu

1 5 10 15

Ser Leu Arg Ile Ser Cys Lys Gly Ser Gly Tyr Ser Phe Ser Thr Ser

20 25 30

Trp Ile Val Trp Val Arg Gln Met Pro Gly Lys Gly Leu Glu Trp Met

35 40 45

Gly Met Ile Asp Pro Ser Asp Ser Tyr Thr Ser Tyr Ser Pro Ser Phe

50 55 60

Gln Gly His Val Thr Ile Ser Ala Asp Lys Ser Ile Ser Thr Ala Tyr

65 70 75 80

Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala Met Tyr Tyr Cys

85 90 95

Ala Arg Leu His Tyr Tyr Asn Ser Glu Glu Phe Asp Val Trp Gly Gln

100 105 110

Gly Thr Met Val Thr Val Ser Ser

115 120

<210> 868

<211> 5

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 868

Thr Ser Trp Ile Val

15

<210> 869

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 869

Met Ile Asp Pro Ser Asp Ser Tyr Thr Ser Tyr Ser Pro Ser Phe Gln

1 5 10 15

Gly

<210> 870

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 870

Leu His Tyr Tyr Asn Ser Glu Glu Phe Asp Val

1 5 10

<210> 871

<211> 109

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 871

Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly

1 5 10 15

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Ser

20 25 30

Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu

35 40 45

Ile Tyr Gly Gln Ser Ser Arg Thr Arg 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 Gln Gln Phe Gly Glu Ser Gln

85 90 95

Leu Phe Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

100 105

<210> 872

<211> 12

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 872

Arg Ala Ser Gln Ser Val Ser Ser Ser Tyr Leu Ala

1 5 10

<210> 873

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 873

Gly Gln Ser Ser Arg Thr Arg

15

<210> 874

<211> 10

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 874

Gln Gln Phe Gly Glu Ser Gln Leu Phe Thr

1 5 10

<210> 875

<211> 120

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 875

Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Glu

1 5 10 15

Ser Leu Arg Ile Ser Cys Lys Gly Ser Gly Tyr Ser Phe Ser Thr Ser

20 25 30

Trp Ile Ser Trp Val Arg Gln Met Pro Gly Lys Gly Leu Glu Trp Met

35 40 45

Gly Met Ile Asp Pro Ser Asp Ser Tyr Thr Ser Tyr Ser Pro Ser Phe

50 55 60

Gln Gly His Val Thr Ile Ser Ala Asp Lys Ser Ile Ser Thr Ala Tyr

65 70 75 80

Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala Met Tyr Tyr Cys

85 90 95

Ala Arg Leu His Tyr Tyr Asn Ser Glu Glu Phe Asp Val Trp Gly Gln

100 105 110

Gly Thr Met Val Thr Val Ser Ser

115 120

<210> 876

<211> 5

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 876

Thr Ser Trp Ile Ser

15

<210> 877

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 877

Met Ile Asp Pro Ser Asp Ser Tyr Thr Ser Tyr Ser Pro Ser Phe Gln

1 5 10 15

Gly

<210> 878

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 878

Leu His Tyr Tyr Asn Ser Glu Glu Phe Asp Val

1 5 10

<210> 879

<211> 109

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 879

Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly

1 5 10 15

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Ser

20 25 30

Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu

35 40 45

Ile Tyr Gly Gln Ser Ser Arg Thr Arg 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 Gln Gln Phe Gly Asn Ser Gln

85 90 95

Leu Phe Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

100 105

<210> 880

<211> 12

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 880

Arg Ala Ser Gln Ser Val Ser Ser Ser Tyr Leu Ala

1 5 10

<210> 881

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 881

Gly Gln Ser Ser Arg Thr Arg

15

<210> 882

<211> 10

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 882

Gln Gln Phe Gly Asn Ser Gln Leu Phe Thr

1 5 10

<210> 883

<211> 120

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 883

Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Glu

1 5 10 15

Ser Leu Arg Ile Ser Cys Lys Gly Ser Gly Tyr Ser Phe Thr Thr Ser

20 25 30

Trp Ile Ser Trp Val Arg Gln Met Pro Gly Lys Gly Leu Glu Trp Met

35 40 45

Gly Met Ile Asp Pro Ser Asp Ser Phe Thr Ser Tyr Ser Pro Ser Phe

50 55 60

Gln Gly His Val Thr Ile Ser Ala Asp Lys Ser Ile Ser Thr Ala Tyr

65 70 75 80

Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala Met Tyr Tyr Cys

85 90 95

Ala Arg Leu His Tyr Tyr His Ser Glu Glu Phe Asp Val Trp Gly Gln

100 105 110

Gly Thr Met Val Thr Val Ser Ser

115 120

<210> 884

<211> 5

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 884

Thr Ser Trp Ile Ser

15

<210> 885

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 885

Met Ile Asp Pro Ser Asp Ser Phe Thr Ser Tyr Ser Pro Ser Phe Gln

1 5 10 15

Gly

<210> 886

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 886

Leu His Tyr Tyr His Ser Glu Glu Phe Asp Val

1 5 10

<210> 887

<211> 109

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 887

Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly

1 5 10 15

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Ser

20 25 30

Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu

35 40 45

Ile Tyr Gly Gln Ser Ser Arg Thr Arg 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 Gln Gln Phe Gly Asn Ser Gln

85 90 95

Leu Phe Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

100 105

<210> 888

<211> 12

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 888

Arg Ala Ser Gln Ser Val Ser Ser Ser Tyr Leu Ala

1 5 10

<210> 889

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 889

Gly Gln Ser Ser Arg Thr Arg

15

<210> 890

<211> 10

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 890

Gln Gln Phe Gly Asn Ser Gln Leu Phe Thr

1 5 10

<210> 891

<211> 120

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 891

Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Glu

1 5 10 15

Ser Leu Arg Ile Ser Cys Lys Gly Ser Gly Tyr Ser Phe Thr Thr Ser

20 25 30

Trp Ile Ser Trp Val Arg Gln Met Pro Gly Lys Gly Leu Glu Trp Met

35 40 45

Gly Met Ile Asp Pro Ser Asp Ser Tyr Thr Ser Tyr Ser Pro Ser Phe

50 55 60

Gln Gly His Val Thr Ile Ser Ala Asp Lys Ser Ile Ser Thr Ala Tyr

65 70 75 80

Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala Met Tyr Tyr Cys

85 90 95

Ala Arg Leu His Tyr Tyr His Ser Glu Glu Phe Asp Val Trp Gly Gln

100 105 110

Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 892

<211> 5

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 892

Thr Ser Trp Ile Ser

15

<210> 893

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 893

Met Ile Asp Pro Ser Asp Ser Tyr Thr Ser Tyr Ser Pro Ser Phe Gln

1 5 10 15

Gly

<210> 894

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 894

Leu His Tyr Tyr His Ser Glu Glu Phe Asp Val

1 5 10

<210> 895

<211> 109

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 895

Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly

1 5 10 15

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Ser

20 25 30

Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu

35 40 45

Ile Tyr Gly Gln Ser Ser Arg Thr Arg 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 Gln Gln Phe Gly Asn Ser Gln

85 90 95

Leu Phe Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

100 105

<210> 896

<211> 12

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 896

Arg Ala Ser Gln Ser Val Ser Ser Ser Tyr Leu Ala

1 5 10

<210> 897

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 897

Gly Gln Ser Ser Arg Thr Arg

15

<210> 898

<211> 10

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 898

Gln Gln Phe Gly Asn Ser Gln Leu Phe Thr

1 5 10

<210> 899

<211> 120

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 899

Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Glu

1 5 10 15

Ser Leu Arg Ile Ser Cys Lys Gly Ser Gly Tyr Ser Phe Thr Thr Ser

20 25 30

Trp Ile Ser Trp Val Arg Gln Met Pro Gly Lys Gly Leu Glu Trp Met

35 40 45

Gly Met Ile Asp Pro Ser Asp Ser Tyr Thr Ser Tyr Ser Pro Ser Phe

50 55 60

Gln Gly His Val Thr Ile Ser Ala Asp Lys Ser Ile Ser Thr Ala Tyr

65 70 75 80

Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala Met Tyr Tyr Cys

85 90 95

Ala Arg Leu His Tyr Tyr His Ser Glu Glu Phe Asp Val Trp Gly Gln

100 105 110

Gly Thr Met Val Thr Val Ser Ser

115 120

<210> 900

<211> 5

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 900

Thr Ser Trp Ile Ser

15

<210> 901

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 901

Met Ile Asp Pro Ser Asp Ser Tyr Thr Ser Tyr Ser Pro Ser Phe Gln

1 5 10 15

Gly

<210> 902

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 902

Leu His Tyr Tyr His Ser Glu Glu Phe Asp Val

1 5 10

<210> 903

<211> 109

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 903

Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly

1 5 10 15

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Ser

20 25 30

Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu

35 40 45

Ile Tyr Gly Gln Ser Ser Arg Thr Arg 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 Gln Gln Phe Gly Asn Ser Gln

85 90 95

Leu Phe Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

100 105

<210> 904

<211> 12

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 904

Arg Ala Ser Gln Ser Val Ser Ser Ser Tyr Leu Ala

1 5 10

<210> 905

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 905

Gly Gln Ser Ser Arg Thr Arg

15

<210> 906

<211> 10

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 906

Gln Gln Phe Gly Asn Ser Gln Leu Phe Thr

1 5 10

<210> 907

<211> 120

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 907

Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Glu

1 5 10 15

Ser Leu Arg Ile Ser Cys Lys Gly Ser Gly Tyr Ser Phe Ser Thr Ser

20 25 30

Trp Ile Ser Trp Val Arg Gln Met Pro Gly Lys Gly Leu Glu Trp Met

35 40 45

Gly Met Ile Asp Pro Ser Asp Ser Phe Thr Ser Tyr Ser Pro Ser Phe

50 55 60

Gln Gly His Val Thr Ile Ser Ala Asp Lys Ser Ile Ser Thr Ala Tyr

65 70 75 80

Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala Met Tyr Tyr Cys

85 90 95

Ala Arg Leu His Tyr Tyr Asn Ser Glu Glu Phe Asp Val Trp Gly Gln

100 105 110

Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 908

<211> 5

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 908

Thr Ser Trp Ile Ser

15

<210> 909

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 909

Met Ile Asp Pro Ser Asp Ser Phe Thr Ser Tyr Ser Pro Ser Phe Gln

1 5 10 15

Gly

<210> 910

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 910

Leu His Tyr Tyr Asn Ser Glu Glu Phe Asp Val

1 5 10

<210> 911

<211> 109

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 911

Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly

1 5 10 15

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Ser

20 25 30

Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu

35 40 45

Ile Tyr Gly Gln Ser Ser Arg Thr Arg 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 Gln Gln Phe Gly Asn Ser Gln

85 90 95

Leu Phe Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

100 105

<210> 912

<211> 12

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 912

Arg Ala Ser Gln Ser Val Ser Ser Ser Tyr Leu Ala

1 5 10

<210> 913

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 913

Gly Gln Ser Ser Arg Thr Arg

15

<210> 914

<211> 10

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 914

Gln Gln Phe Gly Asn Ser Gln Leu Phe Thr

1 5 10

<210> 915

<211> 120

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 915

Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Glu

1 5 10 15

Ser Leu Arg Ile Ser Cys Lys Gly Ser Gly Tyr Ser Phe Ser Thr Ser

20 25 30

Trp Ile Val Trp Val Arg Gln Met Pro Gly Lys Gly Leu Glu Trp Met

35 40 45

Gly Met Ile Asp Pro Ser Asp Ser Tyr Thr Ser Tyr Ser Pro Ser Phe

50 55 60

Gln Gly His Val Thr Ile Ser Ala Asp Lys Ser Ile Ser Thr Ala Tyr

65 70 75 80

Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala Met Tyr Tyr Cys

85 90 95

Ala Arg Leu His Tyr Tyr Asn Ser Glu Glu Phe Asp Val Trp Gly Gln

100 105 110

Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 916

<211> 5

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 916

Thr Ser Trp Ile Val

15

<210> 917

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 917

Met Ile Asp Pro Ser Asp Ser Tyr Thr Ser Tyr Ser Pro Ser Phe Gln

1 5 10 15

Gly

<210> 918

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 918

Leu His Tyr Tyr Asn Ser Glu Glu Phe Asp Val

1 5 10

<210> 919

<211> 109

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 919

Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly

1 5 10 15

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Ser

20 25 30

Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu

35 40 45

Ile Tyr Gly Gln Ser Ser Arg Thr Arg 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 Gln Gln Phe Gly Asn Ser Gln

85 90 95

Leu Phe Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

100 105

<210> 920

<211> 12

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 920

Arg Ala Ser Gln Ser Val Ser Ser Ser Tyr Leu Ala

1 5 10

<210> 921

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 921

Gly Gln Ser Ser Arg Thr Arg

15

<210> 922

<211> 10

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 922

Gln Gln Phe Gly Asn Ser Gln Leu Phe Thr

1 5 10

<210> 923

<211> 120

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 923

Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Glu

1 5 10 15

Ser Leu Arg Ile Ser Cys Lys Gly Ser Gly Tyr Ser Phe Ser Thr Ser

20 25 30

Trp Ile Val Trp Val Arg Gln Met Pro Gly Lys Gly Leu Glu Trp Met

35 40 45

Gly Met Ile Asp Pro Ser Asp Ser Tyr Thr Ser Tyr Ser Pro Ser Phe

50 55 60

Gln Gly His Val Thr Ile Ser Ala Asp Lys Ser Ile Ser Thr Ala Tyr

65 70 75 80

Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala Met Tyr Tyr Cys

85 90 95

Ala Arg Leu His Tyr Tyr Asn Ser Glu Glu Phe Asp Val Trp Gly Gln

100 105 110

Gly Thr Met Val Thr Val Ser Ser

115 120

<210> 924

<211> 5

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 924

Thr Ser Trp Ile Val

15

<210> 925

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 925

Met Ile Asp Pro Ser Asp Ser Tyr Thr Ser Tyr Ser Pro Ser Phe Gln

1 5 10 15

Gly

<210> 926

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 926

Leu His Tyr Tyr Asn Ser Glu Glu Phe Asp Val

1 5 10

<210> 927

<211> 109

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 927

Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly

1 5 10 15

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Ser

20 25 30

Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu

35 40 45

Ile Tyr Gly Gln Ser Ser Arg Thr Arg 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 Gln Gln Phe Gly Asn Ser Gln

85 90 95

Leu Phe Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

100 105

<210> 928

<211> 12

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 928

Arg Ala Ser Gln Ser Val Ser Ser Ser Tyr Leu Ala

1 5 10

<210> 929

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 929

Gly Gln Ser Ser Arg Thr Arg

15

<210> 930

<211> 10

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 930

Gln Gln Phe Gly Asn Ser Gln Leu Phe Thr

1 5 10

<210> 931

<211> 120

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 931

Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Glu

1 5 10 15

Ser Leu Arg Ile Ser Cys Lys Gly Ser Gly Tyr Ser Phe Ser Thr Ser

20 25 30

Trp Ile Ser Trp Val Arg Gln Met Pro Gly Lys Gly Leu Glu Trp Met

35 40 45

Gly Met Ile Asp Pro Ser Asp Ser Tyr Thr Ser Tyr Ser Pro Ser Phe

50 55 60

Gln Gly His Val Thr Ile Ser Ala Asp Lys Ser Ile Ser Thr Ala Tyr

65 70 75 80

Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala Met Tyr Tyr Cys

85 90 95

Ala Arg Leu His Tyr Tyr Asn Ser Glu Glu Phe Asp Val Trp Gly Gln

100 105 110

Gly Thr Met Val Thr Val Ser Ser

115 120

<210> 932

<211> 5

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 932

Thr Ser Trp Ile Ser

15

<210> 933

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 933

Met Ile Asp Pro Ser Asp Ser Tyr Thr Ser Tyr Ser Pro Ser Phe Gln

1 5 10 15

Gly

<210> 934

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 934

Leu His Tyr Tyr Asn Ser Glu Glu Phe Asp Val

1 5 10

<210> 935

<211> 109

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 935

Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly

1 5 10 15

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Ser

20 25 30

Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu

35 40 45

Ile Tyr Gly Gln Ser Ser Arg Thr Arg 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 Gln Gln Phe Gly Gln Ser Gln

85 90 95

Leu Phe Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

100 105

<210> 936

<211> 12

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 936

Arg Ala Ser Gln Ser Val Ser Ser Ser Tyr Leu Ala

1 5 10

<210> 937

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 937

Gly Gln Ser Ser Arg Thr Arg

15

<210> 938

<211> 10

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 938

Gln Gln Phe Gly Gln Ser Gln Leu Phe Thr

1 5 10

<210> 939

<211> 120

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 939

Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Glu

1 5 10 15

Ser Leu Arg Ile Ser Cys Lys Gly Ser Gly Tyr Ser Phe Thr Thr Ser

20 25 30

Trp Ile Ser Trp Val Arg Gln Met Pro Gly Lys Gly Leu Glu Trp Met

35 40 45

Gly Met Ile Asp Pro Ser Asp Ser Phe Thr Ser Tyr Ser Pro Ser Phe

50 55 60

Gln Gly His Val Thr Ile Ser Ala Asp Lys Ser Ile Ser Thr Ala Tyr

65 70 75 80

Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala Met Tyr Tyr Cys

85 90 95

Ala Arg Leu His Tyr Tyr His Ser Glu Glu Phe Asp Val Trp Gly Gln

100 105 110

Gly Thr Met Val Thr Val Ser Ser

115 120

<210> 940

<211> 5

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 940

Thr Ser Trp Ile Ser

15

<210> 941

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 941

Met Ile Asp Pro Ser Asp Ser Phe Thr Ser Tyr Ser Pro Ser Phe Gln

1 5 10 15

Gly

<210> 942

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 942

Leu His Tyr Tyr His Ser Glu Glu Phe Asp Val

1 5 10

<210> 943

<211> 109

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 943

Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly

1 5 10 15

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Ser

20 25 30

Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu

35 40 45

Ile Tyr Gly Gln Ser Ser Arg Thr Arg 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 Gln Gln Phe Gly Gln Ser Gln

85 90 95

Leu Phe Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

100 105

<210> 944

<211> 12

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 944

Arg Ala Ser Gln Ser Val Ser Ser Ser Tyr Leu Ala

1 5 10

<210> 945

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 945

Gly Gln Ser Ser Arg Thr Arg

15

<210> 946

<211> 10

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 946

Gln Gln Phe Gly Gln Ser Gln Leu Phe Thr

1 5 10

<210> 947

<211> 120

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 947

Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Glu

1 5 10 15

Ser Leu Arg Ile Ser Cys Lys Gly Ser Gly Tyr Ser Phe Thr Thr Ser

20 25 30

Trp Ile Ser Trp Val Arg Gln Met Pro Gly Lys Gly Leu Glu Trp Met

35 40 45

Gly Met Ile Asp Pro Ser Asp Ser Tyr Thr Ser Tyr Ser Pro Ser Phe

50 55 60

Gln Gly His Val Thr Ile Ser Ala Asp Lys Ser Ile Ser Thr Ala Tyr

65 70 75 80

Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala Met Tyr Tyr Cys

85 90 95

Ala Arg Leu His Tyr Tyr His Ser Glu Glu Phe Asp Val Trp Gly Gln

100 105 110

Gly Thr Met Val Thr Val Ser Ser

115 120

<210> 948

<211> 5

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 948

Thr Ser Trp Ile Ser

15

<210> 949

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 949

Met Ile Asp Pro Ser Asp Ser Tyr Thr Ser Tyr Ser Pro Ser Phe Gln

1 5 10 15

Gly

<210> 950

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 950

Leu His Tyr Tyr His Ser Glu Glu Phe Asp Val

1 5 10

<210> 951

<211> 109

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 951

Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly

1 5 10 15

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Ser

20 25 30

Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu

35 40 45

Ile Tyr Gly Gln Ser Ser Arg Thr Arg 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 Gln Gln Phe Gly Gln Ser Gln

85 90 95

Leu Phe Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

100 105

<210> 952

<211> 12

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 952

Arg Ala Ser Gln Ser Val Ser Ser Ser Tyr Leu Ala

1 5 10

<210> 953

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 953

Gly Gln Ser Ser Arg Thr Arg

15

<210> 954

<211> 10

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 954

Gln Gln Phe Gly Gln Ser Gln Leu Phe Thr

1 5 10

<210> 955

<211> 120

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 955

Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Glu

1 5 10 15

Ser Leu Arg Ile Ser Cys Lys Gly Ser Gly Tyr Ser Phe Ser Thr Ser

20 25 30

Trp Ile Ser Trp Val Arg Gln Met Pro Gly Lys Gly Leu Glu Trp Met

35 40 45

Gly Met Ile Asp Pro Ser Asp Ser Phe Thr Ser Tyr Ser Pro Ser Phe

50 55 60

Gln Gly His Val Thr Ile Ser Ala Asp Lys Ser Ile Ser Thr Ala Tyr

65 70 75 80

Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala Met Tyr Tyr Cys

85 90 95

Ala Arg Leu His Tyr Tyr Asn Ser Glu Glu Phe Asp Val Trp Gly Gln

100 105 110

Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 956

<211> 5

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 956

Thr Ser Trp Ile Ser

15

<210> 957

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 957

Met Ile Asp Pro Ser Asp Ser Phe Thr Ser Tyr Ser Pro Ser Phe Gln

1 5 10 15

Gly

<210> 958

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 958

Leu His Tyr Tyr Asn Ser Glu Glu Phe Asp Val

1 5 10

<210> 959

<211> 109

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 959

Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly

1 5 10 15

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Ser

20 25 30

Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu

35 40 45

Ile Tyr Gly Gln Ser Ser Arg Thr Arg 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 Gln Gln Phe Gly Gln Ser Gln

85 90 95

Leu Phe Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

100 105

<210> 960

<211> 12

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 960

Arg Ala Ser Gln Ser Val Ser Ser Ser Tyr Leu Ala

1 5 10

<210> 961

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 961

Gly Gln Ser Ser Arg Thr Arg

15

<210> 962

<211> 10

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 962

Gln Gln Phe Gly Gln Ser Gln Leu Phe Thr

1 5 10

<210> 963

<211> 120

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 963

Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Glu

1 5 10 15

Ser Leu Arg Ile Ser Cys Lys Gly Ser Gly Tyr Ser Phe Ser Thr Ser

20 25 30

Trp Ile Val Trp Val Arg Gln Met Pro Gly Lys Gly Leu Glu Trp Met

35 40 45

Gly Met Ile Asp Pro Ser Asp Ser Tyr Thr Ser Tyr Ser Pro Ser Phe

50 55 60

Gln Gly His Val Thr Ile Ser Ala Asp Lys Ser Ile Ser Thr Ala Tyr

65 70 75 80

Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala Met Tyr Tyr Cys

85 90 95

Ala Arg Leu His Tyr Tyr Asn Ser Glu Glu Phe Asp Val Trp Gly Gln

100 105 110

Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 964

<211> 5

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 964

Thr Ser Trp Ile Val

15

<210> 965

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 965

Met Ile Asp Pro Ser Asp Ser Tyr Thr Ser Tyr Ser Pro Ser Phe Gln

1 5 10 15

Gly

<210> 966

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 966

Leu His Tyr Tyr Asn Ser Glu Glu Phe Asp Val

1 5 10

<210> 967

<211> 109

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 967

Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly

1 5 10 15

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Ser

20 25 30

Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu

35 40 45

Ile Tyr Gly Gln Ser Ser Arg Thr Arg 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 Gln Gln Phe Gly Gln Ser Gln

85 90 95

Leu Phe Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

100 105

<210> 968

<211> 12

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 968

Arg Ala Ser Gln Ser Val Ser Ser Ser Tyr Leu Ala

1 5 10

<210> 969

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 969

Gly Gln Ser Ser Arg Thr Arg

15

<210> 970

<211> 10

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 970

Gln Gln Phe Gly Gln Ser Gln Leu Phe Thr

1 5 10

<210> 971

<211> 120

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 971

Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Glu

1 5 10 15

Ser Leu Arg Ile Ser Cys Lys Gly Ser Gly Tyr Ser Phe Ser Thr Ser

20 25 30

Trp Ile Val Trp Val Arg Gln Met Pro Gly Lys Gly Leu Glu Trp Met

35 40 45

Gly Met Ile Asp Pro Ser Asp Ser Tyr Thr Ser Tyr Ser Pro Ser Phe

50 55 60

Gln Gly His Val Thr Ile Ser Ala Asp Lys Ser Ile Ser Thr Ala Tyr

65 70 75 80

Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala Met Tyr Tyr Cys

85 90 95

Ala Arg Leu His Tyr Tyr Asn Ser Glu Glu Phe Asp Val Trp Gly Gln

100 105 110

Gly Thr Met Val Thr Val Ser Ser

115 120

<210> 972

<211> 5

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 972

Thr Ser Trp Ile Val

15

<210> 973

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 973

Met Ile Asp Pro Ser Asp Ser Tyr Thr Ser Tyr Ser Pro Ser Phe Gln

1 5 10 15

Gly

<210> 974

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 974

Leu His Tyr Tyr Asn Ser Glu Glu Phe Asp Val

1 5 10

<210> 975

<211> 109

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 975

Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly

1 5 10 15

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Ser

20 25 30

Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu

35 40 45

Ile Tyr Gly Gln Ser Ser Arg Thr Arg 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 Gln Gln Phe Gly Gln Ser Gln

85 90 95

Leu Phe Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

100 105

<210> 976

<211> 12

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 976

Arg Ala Ser Gln Ser Val Ser Ser Ser Tyr Leu Ala

1 5 10

<210> 977

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 977

Gly Gln Ser Ser Arg Thr Arg

15

<210> 978

<211> 10

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 978

Gln Gln Phe Gly Gln Ser Gln Leu Phe Thr

1 5 10

<210> 979

<211> 120

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 979

Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Glu

1 5 10 15

Ser Leu Arg Ile Ser Cys Lys Gly Ser Gly Tyr Ser Phe Ser Thr Ser

20 25 30

Trp Ile Ser Trp Val Arg Gln Met Pro Gly Lys Gly Leu Glu Trp Met

35 40 45

Gly Met Ile Asp Pro Ser Asp Ser Tyr Thr Ser Tyr Ser Pro Ser Phe

50 55 60

Gln Gly His Val Thr Ile Ser Ala Asp Lys Ser Ile Ser Thr Ala Tyr

65 70 75 80

Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala Met Tyr Tyr Cys

85 90 95

Ala Arg Leu His Tyr Tyr Asn Ser Glu Glu Phe Asp Val Trp Gly Gln

100 105 110

Gly Thr Met Val Thr Val Ser Ser

115 120

<210> 980

<211> 5

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 980

Thr Ser Trp Ile Ser

15

<210> 981

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 981

Met Ile Asp Pro Ser Asp Ser Tyr Thr Ser Tyr Ser Pro Ser Phe Gln

1 5 10 15

Gly

<210> 982

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 982

Leu His Tyr Tyr Asn Ser Glu Glu Phe Asp Val

1 5 10

<210> 983

<211> 109

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 983

Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly

1 5 10 15

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Ser

20 25 30

Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu

35 40 45

Ile Tyr Gly Gln Ser Ser Arg Thr Arg 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 Gln Gln Phe Gly Asp Ala Gln

85 90 95

Leu Phe Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

100 105

<210> 984

<211> 12

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 984

Arg Ala Ser Gln Ser Val Ser Ser Ser Tyr Leu Ala

1 5 10

<210> 985

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 985

Gly Gln Ser Ser Arg Thr Arg

15

<210> 986

<211> 10

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 986

Gln Gln Phe Gly Asp Ala Gln Leu Phe Thr

1 5 10

<210> 987

<211> 120

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 987

Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Glu

1 5 10 15

Ser Leu Arg Ile Ser Cys Lys Gly Ser Gly Tyr Ser Phe Thr Thr Ser

20 25 30

Trp Ile Ser Trp Val Arg Gln Met Pro Gly Lys Gly Leu Glu Trp Met

35 40 45

Gly Met Ile Asp Pro Ser Asp Ser Phe Thr Ser Tyr Ser Pro Ser Phe

50 55 60

Gln Gly His Val Thr Ile Ser Ala Asp Lys Ser Ile Ser Thr Ala Tyr

65 70 75 80

Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala Met Tyr Tyr Cys

85 90 95

Ala Arg Leu His Tyr Tyr His Ser Glu Glu Phe Asp Val Trp Gly Gln

100 105 110

Gly Thr Met Val Thr Val Ser Ser

115 120

<210> 988

<211> 5

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 988

Thr Ser Trp Ile Ser

15

<210> 989

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 989

Met Ile Asp Pro Ser Asp Ser Phe Thr Ser Tyr Ser Pro Ser Phe Gln

1 5 10 15

Gly

<210> 990

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 990

Leu His Tyr Tyr His Ser Glu Glu Phe Asp Val

1 5 10

<210> 991

<211> 109

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 991

Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly

1 5 10 15

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Ser

20 25 30

Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu

35 40 45

Ile Tyr Gly Gln Ser Ser Arg Thr Arg 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 Gln Gln Phe Gly Asp Ala Gln

85 90 95

Leu Phe Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

100 105

<210> 992

<211> 12

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 992

Arg Ala Ser Gln Ser Val Ser Ser Ser Tyr Leu Ala

1 5 10

<210> 993

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 993

Gly Gln Ser Ser Arg Thr Arg

15

<210> 994

<211> 10

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 994

Gln Gln Phe Gly Asp Ala Gln Leu Phe Thr

1 5 10

<210> 995

<211> 120

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 995

Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Glu

1 5 10 15

Ser Leu Arg Ile Ser Cys Lys Gly Ser Gly Tyr Ser Phe Thr Thr Ser

20 25 30

Trp Ile Ser Trp Val Arg Gln Met Pro Gly Lys Gly Leu Glu Trp Met

35 40 45

Gly Met Ile Asp Pro Ser Asp Ser Tyr Thr Ser Tyr Ser Pro Ser Phe

50 55 60

Gln Gly His Val Thr Ile Ser Ala Asp Lys Ser Ile Ser Thr Ala Tyr

65 70 75 80

Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala Met Tyr Tyr Cys

85 90 95

Ala Arg Leu His Tyr Tyr His Ser Glu Glu Phe Asp Val Trp Gly Gln

100 105 110

Gly Thr Met Val Thr Val Ser Ser

115 120

<210> 996

<211> 5

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 996

Thr Ser Trp Ile Ser

15

<210> 997

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 997

Met Ile Asp Pro Ser Asp Ser Tyr Thr Ser Tyr Ser Pro Ser Phe Gln

1 5 10 15

Gly

<210> 998

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 998

Leu His Tyr Tyr His Ser Glu Glu Phe Asp Val

1 5 10

<210> 999

<211> 109

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 999

Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly

1 5 10 15

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Ser

20 25 30

Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu

35 40 45

Ile Tyr Gly Gln Ser Ser Arg Thr Arg 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 Gln Gln Phe Gly Asp Ala Gln

85 90 95

Leu Phe Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

100 105

<210> 1000

<211> 12

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1000

Arg Ala Ser Gln Ser Val Ser Ser Ser Tyr Leu Ala

1 5 10

<210> 1001

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1001

Gly Gln Ser Ser Arg Thr Arg

15

<210> 1002

<211> 10

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1002

Gln Gln Phe Gly Asp Ala Gln Leu Phe Thr

1 5 10

<210> 1003

<211> 120

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1003

Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Glu

1 5 10 15

Ser Leu Arg Ile Ser Cys Lys Gly Ser Gly Tyr Ser Phe Ser Thr Ser

20 25 30

Trp Ile Ser Trp Val Arg Gln Met Pro Gly Lys Gly Leu Glu Trp Met

35 40 45

Gly Met Ile Asp Pro Ser Asp Ser Phe Thr Ser Tyr Ser Pro Ser Phe

50 55 60

Gln Gly His Val Thr Ile Ser Ala Asp Lys Ser Ile Ser Thr Ala Tyr

65 70 75 80

Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala Met Tyr Tyr Cys

85 90 95

Ala Arg Leu His Tyr Tyr Asn Ser Glu Glu Phe Asp Val Trp Gly Gln

100 105 110

Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 1004

<211> 5

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1004

Thr Ser Trp Ile Ser

15

<210> 1005

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1005

Met Ile Asp Pro Ser Asp Ser Phe Thr Ser Tyr Ser Pro Ser Phe Gln

1 5 10 15

Gly

<210> 1006

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1006

Leu His Tyr Tyr Asn Ser Glu Glu Phe Asp Val

1 5 10

<210> 1007

<211> 109

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1007

Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly

1 5 10 15

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Ser

20 25 30

Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu

35 40 45

Ile Tyr Gly Gln Ser Ser Arg Thr Arg 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 Gln Gln Phe Gly Asp Ala Gln

85 90 95

Leu Phe Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

100 105

<210> 1008

<211> 12

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1008

Arg Ala Ser Gln Ser Val Ser Ser Ser Tyr Leu Ala

1 5 10

<210> 1009

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1009

Gly Gln Ser Ser Arg Thr Arg

15

<210> 1010

<211> 10

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1010

Gln Gln Phe Gly Asp Ala Gln Leu Phe Thr

1 5 10

<210> 1011

<211> 120

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1011

Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Glu

1 5 10 15

Ser Leu Arg Ile Ser Cys Lys Gly Ser Gly Tyr Ser Phe Ser Thr Ser

20 25 30

Trp Ile Val Trp Val Arg Gln Met Pro Gly Lys Gly Leu Glu Trp Met

35 40 45

Gly Met Ile Asp Pro Ser Asp Ser Tyr Thr Ser Tyr Ser Pro Ser Phe

50 55 60

Gln Gly His Val Thr Ile Ser Ala Asp Lys Ser Ile Ser Thr Ala Tyr

65 70 75 80

Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala Met Tyr Tyr Cys

85 90 95

Ala Arg Leu His Tyr Tyr Asn Ser Glu Glu Phe Asp Val Trp Gly Gln

100 105 110

Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 1012

<211> 5

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1012

Thr Ser Trp Ile Val

15

<210> 1013

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1013

Met Ile Asp Pro Ser Asp Ser Tyr Thr Ser Tyr Ser Pro Ser Phe Gln

1 5 10 15

Gly

<210> 1014

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1014

Leu His Tyr Tyr Asn Ser Glu Glu Phe Asp Val

1 5 10

<210> 1015

<211> 109

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1015

Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly

1 5 10 15

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Ser

20 25 30

Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu

35 40 45

Ile Tyr Gly Gln Ser Ser Arg Thr Arg 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 Gln Gln Phe Gly Asp Ala Gln

85 90 95

Leu Phe Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

100 105

<210> 1016

<211> 12

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1016

Arg Ala Ser Gln Ser Val Ser Ser Ser Tyr Leu Ala

1 5 10

<210> 1017

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1017

Gly Gln Ser Ser Arg Thr Arg

15

<210> 1018

<211> 10

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1018

Gln Gln Phe Gly Asp Ala Gln Leu Phe Thr

1 5 10

<210> 1019

<211> 120

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1019

Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Glu

1 5 10 15

Ser Leu Arg Ile Ser Cys Lys Gly Ser Gly Tyr Ser Phe Ser Thr Ser

20 25 30

Trp Ile Val Trp Val Arg Gln Met Pro Gly Lys Gly Leu Glu Trp Met

35 40 45

Gly Met Ile Asp Pro Ser Asp Ser Tyr Thr Ser Tyr Ser Pro Ser Phe

50 55 60

Gln Gly His Val Thr Ile Ser Ala Asp Lys Ser Ile Ser Thr Ala Tyr

65 70 75 80

Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala Met Tyr Tyr Cys

85 90 95

Ala Arg Leu His Tyr Tyr Asn Ser Glu Glu Phe Asp Val Trp Gly Gln

100 105 110

Gly Thr Met Val Thr Val Ser Ser

115 120

<210> 1020

<211> 5

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1020

Thr Ser Trp Ile Val

15

<210> 1021

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1021

Met Ile Asp Pro Ser Asp Ser Tyr Thr Ser Tyr Ser Pro Ser Phe Gln

1 5 10 15

Gly

<210> 1022

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1022

Leu His Tyr Tyr Asn Ser Glu Glu Phe Asp Val

1 5 10

<210> 1023

<211> 109

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1023

Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly

1 5 10 15

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Ser

20 25 30

Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu

35 40 45

Ile Tyr Gly Gln Ser Ser Arg Thr Arg 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 Gln Gln Phe Gly Asp Ala Gln

85 90 95

Leu Phe Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

100 105

<210> 1024

<211> 12

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1024

Arg Ala Ser Gln Ser Val Ser Ser Ser Tyr Leu Ala

1 5 10

<210> 1025

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1025

Gly Gln Ser Ser Arg Thr Arg

15

<210> 1026

<211> 10

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1026

Gln Gln Phe Gly Asp Ala Gln Leu Phe Thr

1 5 10

<210> 1027

<211> 120

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1027

Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Glu

1 5 10 15

Ser Leu Arg Ile Ser Cys Lys Gly Ser Gly Tyr Ser Phe Ser Thr Ser

20 25 30

Trp Ile Ser Trp Val Arg Gln Met Pro Gly Lys Gly Leu Glu Trp Met

35 40 45

Gly Met Ile Asp Pro Ser Asp Ser Tyr Thr Ser Tyr Ser Pro Ser Phe

50 55 60

Gln Gly His Val Thr Ile Ser Ala Asp Lys Ser Ile Ser Thr Ala Tyr

65 70 75 80

Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala Met Tyr Tyr Cys

85 90 95

Ala Arg Leu His Tyr Tyr Asn Ser Glu Glu Phe Asp Val Trp Gly Gln

100 105 110

Gly Thr Met Val Thr Val Ser Ser

115 120

<210> 1028

<211> 5

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1028

Thr Ser Trp Ile Ser

15

<210> 1029

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1029

Met Ile Asp Pro Ser Asp Ser Tyr Thr Ser Tyr Ser Pro Ser Phe Gln

1 5 10 15

Gly

<210> 1030

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1030

Leu His Tyr Tyr Asn Ser Glu Glu Phe Asp Val

1 5 10

<210> 1031

<211> 109

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1031

Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly

1 5 10 15

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Ser

20 25 30

Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu

35 40 45

Ile Tyr Gly Gln Ser Ser Arg Thr Arg 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 Gln Gln Phe Gly Asp Thr Gln

85 90 95

Leu Phe Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

100 105

<210> 1032

<211> 12

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1032

Arg Ala Ser Gln Ser Val Ser Ser Ser Tyr Leu Ala

1 5 10

<210> 1033

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1033

Gly Gln Ser Ser Arg Thr Arg

15

<210> 1034

<211> 10

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1034

Gln Gln Phe Gly Asp Thr Gln Leu Phe Thr

1 5 10

<210> 1035

<211> 120

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1035

Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Glu

1 5 10 15

Ser Leu Arg Ile Ser Cys Lys Gly Ser Gly Tyr Ser Phe Thr Thr Ser

20 25 30

Trp Ile Ser Trp Val Arg Gln Met Pro Gly Lys Gly Leu Glu Trp Met

35 40 45

Gly Met Ile Asp Pro Ser Asp Ser Phe Thr Ser Tyr Ser Pro Ser Phe

50 55 60

Gln Gly His Val Thr Ile Ser Ala Asp Lys Ser Ile Ser Thr Ala Tyr

65 70 75 80

Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala Met Tyr Tyr Cys

85 90 95

Ala Arg Leu His Tyr Tyr His Ser Glu Glu Phe Asp Val Trp Gly Gln

100 105 110

Gly Thr Met Val Thr Val Ser Ser

115 120

<210> 1036

<211> 5

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1036

Thr Ser Trp Ile Ser

15

<210> 1037

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1037

Met Ile Asp Pro Ser Asp Ser Phe Thr Ser Tyr Ser Pro Ser Phe Gln

1 5 10 15

Gly

<210> 1038

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1038

Leu His Tyr Tyr His Ser Glu Glu Phe Asp Val

1 5 10

<210> 1039

<211> 109

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1039

Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly

1 5 10 15

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Ser

20 25 30

Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu

35 40 45

Ile Tyr Gly Gln Ser Ser Arg Thr Arg 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 Gln Gln Phe Gly Asp Thr Gln

85 90 95

Leu Phe Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

100 105

<210> 1040

<211> 12

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1040

Arg Ala Ser Gln Ser Val Ser Ser Ser Tyr Leu Ala

1 5 10

<210> 1041

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1041

Gly Gln Ser Ser Arg Thr Arg

15

<210> 1042

<211> 10

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1042

Gln Gln Phe Gly Asp Thr Gln Leu Phe Thr

1 5 10

<210> 1043

<211> 120

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1043

Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Glu

1 5 10 15

Ser Leu Arg Ile Ser Cys Lys Gly Ser Gly Tyr Ser Phe Thr Thr Ser

20 25 30

Trp Ile Ser Trp Val Arg Gln Met Pro Gly Lys Gly Leu Glu Trp Met

35 40 45

Gly Met Ile Asp Pro Ser Asp Ser Tyr Thr Ser Tyr Ser Pro Ser Phe

50 55 60

Gln Gly His Val Thr Ile Ser Ala Asp Lys Ser Ile Ser Thr Ala Tyr

65 70 75 80

Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala Met Tyr Tyr Cys

85 90 95

Ala Arg Leu His Tyr Tyr His Ser Glu Glu Phe Asp Val Trp Gly Gln

100 105 110

Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 1044

<211> 5

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1044

Thr Ser Trp Ile Ser

15

<210> 1045

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1045

Met Ile Asp Pro Ser Asp Ser Tyr Thr Ser Tyr Ser Pro Ser Phe Gln

1 5 10 15

Gly

<210> 1046

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1046

Leu His Tyr Tyr His Ser Glu Glu Phe Asp Val

1 5 10

<210> 1047

<211> 109

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1047

Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly

1 5 10 15

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Ser

20 25 30

Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu

35 40 45

Ile Tyr Gly Gln Ser Ser Arg Thr Arg 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 Gln Gln Phe Gly Asp Thr Gln

85 90 95

Leu Phe Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

100 105

<210> 1048

<211> 12

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1048

Arg Ala Ser Gln Ser Val Ser Ser Ser Tyr Leu Ala

1 5 10

<210> 1049

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1049

Gly Gln Ser Ser Arg Thr Arg

15

<210> 1050

<211> 10

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1050

Gln Gln Phe Gly Asp Thr Gln Leu Phe Thr

1 5 10

<210> 1051

<211> 120

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1051

Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Glu

1 5 10 15

Ser Leu Arg Ile Ser Cys Lys Gly Ser Gly Tyr Ser Phe Thr Thr Ser

20 25 30

Trp Ile Ser Trp Val Arg Gln Met Pro Gly Lys Gly Leu Glu Trp Met

35 40 45

Gly Met Ile Asp Pro Ser Asp Ser Tyr Thr Ser Tyr Ser Pro Ser Phe

50 55 60

Gln Gly His Val Thr Ile Ser Ala Asp Lys Ser Ile Ser Thr Ala Tyr

65 70 75 80

Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala Met Tyr Tyr Cys

85 90 95

Ala Arg Leu His Tyr Tyr His Ser Glu Glu Phe Asp Val Trp Gly Gln

100 105 110

Gly Thr Met Val Thr Val Ser Ser

115 120

<210> 1052

<211> 5

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1052

Thr Ser Trp Ile Ser

15

<210> 1053

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1053

Met Ile Asp Pro Ser Asp Ser Tyr Thr Ser Tyr Ser Pro Ser Phe Gln

1 5 10 15

Gly

<210> 1054

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1054

Leu His Tyr Tyr His Ser Glu Glu Phe Asp Val

1 5 10

<210> 1055

<211> 109

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1055

Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly

1 5 10 15

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Ser

20 25 30

Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu

35 40 45

Ile Tyr Gly Gln Ser Ser Arg Thr Arg 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 Gln Gln Phe Gly Asp Thr Gln

85 90 95

Leu Phe Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

100 105

<210> 1056

<211> 12

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1056

Arg Ala Ser Gln Ser Val Ser Ser Ser Tyr Leu Ala

1 5 10

<210> 1057

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1057

Gly Gln Ser Ser Arg Thr Arg

15

<210> 1058

<211> 10

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1058

Gln Gln Phe Gly Asp Thr Gln Leu Phe Thr

1 5 10

<210> 1059

<211> 120

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1059

Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Glu

1 5 10 15

Ser Leu Arg Ile Ser Cys Lys Gly Ser Gly Tyr Ser Phe Ser Thr Ser

20 25 30

Trp Ile Ser Trp Val Arg Gln Met Pro Gly Lys Gly Leu Glu Trp Met

35 40 45

Gly Met Ile Asp Pro Ser Asp Ser Phe Thr Ser Tyr Ser Pro Ser Phe

50 55 60

Gln Gly His Val Thr Ile Ser Ala Asp Lys Ser Ile Ser Thr Ala Tyr

65 70 75 80

Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala Met Tyr Tyr Cys

85 90 95

Ala Arg Leu His Tyr Tyr Asn Ser Glu Glu Phe Asp Val Trp Gly Gln

100 105 110

Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 1060

<211> 5

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1060

Thr Ser Trp Ile Ser

15

<210> 1061

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1061

Met Ile Asp Pro Ser Asp Ser Phe Thr Ser Tyr Ser Pro Ser Phe Gln

1 5 10 15

Gly

<210> 1062

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1062

Leu His Tyr Tyr Asn Ser Glu Glu Phe Asp Val

1 5 10

<210> 1063

<211> 109

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1063

Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly

1 5 10 15

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Ser

20 25 30

Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu

35 40 45

Ile Tyr Gly Gln Ser Ser Arg Thr Arg 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 Gln Gln Phe Gly Asp Thr Gln

85 90 95

Leu Phe Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

100 105

<210> 1064

<211> 12

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1064

Arg Ala Ser Gln Ser Val Ser Ser Ser Tyr Leu Ala

1 5 10

<210> 1065

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1065

Gly Gln Ser Ser Arg Thr Arg

15

<210> 1066

<211> 10

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1066

Gln Gln Phe Gly Asp Thr Gln Leu Phe Thr

1 5 10

<210> 1067

<211> 120

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1067

Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Glu

1 5 10 15

Ser Leu Arg Ile Ser Cys Lys Gly Ser Gly Tyr Ser Phe Ser Thr Ser

20 25 30

Trp Ile Val Trp Val Arg Gln Met Pro Gly Lys Gly Leu Glu Trp Met

35 40 45

Gly Met Ile Asp Pro Ser Asp Ser Tyr Thr Ser Tyr Ser Pro Ser Phe

50 55 60

Gln Gly His Val Thr Ile Ser Ala Asp Lys Ser Ile Ser Thr Ala Tyr

65 70 75 80

Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala Met Tyr Tyr Cys

85 90 95

Ala Arg Leu His Tyr Tyr Asn Ser Glu Glu Phe Asp Val Trp Gly Gln

100 105 110

Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 1068

<211> 5

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1068

Thr Ser Trp Ile Val

15

<210> 1069

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1069

Met Ile Asp Pro Ser Asp Ser Tyr Thr Ser Tyr Ser Pro Ser Phe Gln

1 5 10 15

Gly

<210> 1070

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1070

Leu His Tyr Tyr Asn Ser Glu Glu Phe Asp Val

1 5 10

<210> 1071

<211> 109

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1071

Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly

1 5 10 15

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Ser

20 25 30

Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu

35 40 45

Ile Tyr Gly Gln Ser Ser Arg Thr Arg 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 Gln Gln Phe Gly Asp Thr Gln

85 90 95

Leu Phe Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

100 105

<210> 1072

<211> 12

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1072

Arg Ala Ser Gln Ser Val Ser Ser Ser Tyr Leu Ala

1 5 10

<210> 1073

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1073

Gly Gln Ser Ser Arg Thr Arg

15

<210> 1074

<211> 10

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1074

Gln Gln Phe Gly Asp Thr Gln Leu Phe Thr

1 5 10

<210> 1075

<211> 120

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1075

Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Glu

1 5 10 15

Ser Leu Arg Ile Ser Cys Lys Gly Ser Gly Tyr Ser Phe Ser Thr Ser

20 25 30

Trp Ile Val Trp Val Arg Gln Met Pro Gly Lys Gly Leu Glu Trp Met

35 40 45

Gly Met Ile Asp Pro Ser Asp Ser Tyr Thr Ser Tyr Ser Pro Ser Phe

50 55 60

Gln Gly His Val Thr Ile Ser Ala Asp Lys Ser Ile Ser Thr Ala Tyr

65 70 75 80

Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala Met Tyr Tyr Cys

85 90 95

Ala Arg Leu His Tyr Tyr Asn Ser Glu Glu Phe Asp Val Trp Gly Gln

100 105 110

Gly Thr Met Val Thr Val Ser Ser

115 120

<210> 1076

<211> 5

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1076

Thr Ser Trp Ile Val

15

<210> 1077

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1077

Met Ile Asp Pro Ser Asp Ser Tyr Thr Ser Tyr Ser Pro Ser Phe Gln

1 5 10 15

Gly

<210> 1078

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1078

Leu His Tyr Tyr Asn Ser Glu Glu Phe Asp Val

1 5 10

<210> 1079

<211> 109

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1079

Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly

1 5 10 15

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Ser

20 25 30

Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu

35 40 45

Ile Tyr Gly Gln Ser Ser Arg Thr Arg 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 Gln Gln Phe Gly Asp Thr Gln

85 90 95

Leu Phe Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

100 105

<210> 1080

<211> 12

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1080

Arg Ala Ser Gln Ser Val Ser Ser Ser Tyr Leu Ala

1 5 10

<210> 1081

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1081

Gly Gln Ser Ser Arg Thr Arg

15

<210> 1082

<211> 10

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1082

Gln Gln Phe Gly Asp Thr Gln Leu Phe Thr

1 5 10

<210> 1083

<211> 120

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1083

Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Glu

1 5 10 15

Ser Leu Arg Ile Ser Cys Lys Gly Ser Gly Tyr Ser Phe Ser Thr Ser

20 25 30

Trp Ile Ser Trp Val Arg Gln Met Pro Gly Lys Gly Leu Glu Trp Met

35 40 45

Gly Met Ile Asp Pro Ser Asp Ser Tyr Thr Ser Tyr Ser Pro Ser Phe

50 55 60

Gln Gly His Val Thr Ile Ser Ala Asp Lys Ser Ile Ser Thr Ala Tyr

65 70 75 80

Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala Met Tyr Tyr Cys

85 90 95

Ala Arg Leu His Tyr Tyr Asn Ser Glu Glu Phe Asp Val Trp Gly Gln

100 105 110

Gly Thr Met Val Thr Val Ser Ser

115 120

<210> 1084

<211> 5

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1084

Thr Ser Trp Ile Ser

15

<210> 1085

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1085

Met Ile Asp Pro Ser Asp Ser Tyr Thr Ser Tyr Ser Pro Ser Phe Gln

1 5 10 15

Gly

<210> 1086

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1086

Leu His Tyr Tyr Asn Ser Glu Glu Phe Asp Val

1 5 10

<210> 1087

<211> 109

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1087

Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly

1 5 10 15

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Ser

20 25 30

Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu

35 40 45

Ile Tyr Gly Gln Ser Ser Arg Thr Arg 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 Gln Gln Phe Gly Asp Asn Gln

85 90 95

Leu Phe Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

100 105

<210> 1088

<211> 12

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1088

Arg Ala Ser Gln Ser Val Ser Ser Ser Tyr Leu Ala

1 5 10

<210> 1089

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1089

Gly Gln Ser Ser Arg Thr Arg

15

<210> 1090

<211> 10

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1090

Gln Gln Phe Gly Asp Asn Gln Leu Phe Thr

1 5 10

<210> 1091

<211> 120

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1091

Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Glu

1 5 10 15

Ser Leu Arg Ile Ser Cys Lys Gly Ser Gly Tyr Ser Phe Thr Thr Ser

20 25 30

Trp Ile Ser Trp Val Arg Gln Met Pro Gly Lys Gly Leu Glu Trp Met

35 40 45

Gly Met Ile Asp Pro Ser Asp Ser Phe Thr Ser Tyr Ser Pro Ser Phe

50 55 60

Gln Gly His Val Thr Ile Ser Ala Asp Lys Ser Ile Ser Thr Ala Tyr

65 70 75 80

Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala Met Tyr Tyr Cys

85 90 95

Ala Arg Leu His Tyr Tyr His Ser Glu Glu Phe Asp Val Trp Gly Gln

100 105 110

Gly Thr Met Val Thr Val Ser Ser

115 120

<210> 1092

<211> 5

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1092

Thr Ser Trp Ile Ser

15

<210> 1093

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1093

Met Ile Asp Pro Ser Asp Ser Phe Thr Ser Tyr Ser Pro Ser Phe Gln

1 5 10 15

Gly

<210> 1094

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1094

Leu His Tyr Tyr His Ser Glu Glu Phe Asp Val

1 5 10

<210> 1095

<211> 109

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1095

Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly

1 5 10 15

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Ser

20 25 30

Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu

35 40 45

Ile Tyr Gly Gln Ser Ser Arg Thr Arg 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 Gln Gln Phe Gly Asp Asn Gln

85 90 95

Leu Phe Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

100 105

<210> 1096

<211> 12

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1096

Arg Ala Ser Gln Ser Val Ser Ser Ser Tyr Leu Ala

1 5 10

<210> 1097

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1097

Gly Gln Ser Ser Arg Thr Arg

15

<210> 1098

<211> 10

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1098

Gln Gln Phe Gly Asp Asn Gln Leu Phe Thr

1 5 10

<210> 1099

<211> 120

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1099

Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Glu

1 5 10 15

Ser Leu Arg Ile Ser Cys Lys Gly Ser Gly Tyr Ser Phe Thr Thr Ser

20 25 30

Trp Ile Ser Trp Val Arg Gln Met Pro Gly Lys Gly Leu Glu Trp Met

35 40 45

Gly Met Ile Asp Pro Ser Asp Ser Tyr Thr Ser Tyr Ser Pro Ser Phe

50 55 60

Gln Gly His Val Thr Ile Ser Ala Asp Lys Ser Ile Ser Thr Ala Tyr

65 70 75 80

Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala Met Tyr Tyr Cys

85 90 95

Ala Arg Leu His Tyr Tyr His Ser Glu Glu Phe Asp Val Trp Gly Gln

100 105 110

Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 1100

<211> 5

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1100

Thr Ser Trp Ile Ser

15

<210> 1101

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1101

Met Ile Asp Pro Ser Asp Ser Tyr Thr Ser Tyr Ser Pro Ser Phe Gln

1 5 10 15

Gly

<210> 1102

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1102

Leu His Tyr Tyr His Ser Glu Glu Phe Asp Val

1 5 10

<210> 1103

<211> 109

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1103

Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly

1 5 10 15

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Ser

20 25 30

Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu

35 40 45

Ile Tyr Gly Gln Ser Ser Arg Thr Arg 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 Gln Gln Phe Gly Asp Asn Gln

85 90 95

Leu Phe Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

100 105

<210> 1104

<211> 12

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1104

Arg Ala Ser Gln Ser Val Ser Ser Ser Tyr Leu Ala

1 5 10

<210> 1105

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1105

Gly Gln Ser Ser Arg Thr Arg

15

<210> 1106

<211> 10

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1106

Gln Gln Phe Gly Asp Asn Gln Leu Phe Thr

1 5 10

<210> 1107

<211> 120

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1107

Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Glu

1 5 10 15

Ser Leu Arg Ile Ser Cys Lys Gly Ser Gly Tyr Ser Phe Thr Thr Ser

20 25 30

Trp Ile Ser Trp Val Arg Gln Met Pro Gly Lys Gly Leu Glu Trp Met

35 40 45

Gly Met Ile Asp Pro Ser Asp Ser Tyr Thr Ser Tyr Ser Pro Ser Phe

50 55 60

Gln Gly His Val Thr Ile Ser Ala Asp Lys Ser Ile Ser Thr Ala Tyr

65 70 75 80

Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala Met Tyr Tyr Cys

85 90 95

Ala Arg Leu His Tyr Tyr His Ser Glu Glu Phe Asp Val Trp Gly Gln

100 105 110

Gly Thr Met Val Thr Val Ser Ser

115 120

<210> 1108

<211> 5

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1108

Thr Ser Trp Ile Ser

15

<210> 1109

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1109

Met Ile Asp Pro Ser Asp Ser Tyr Thr Ser Tyr Ser Pro Ser Phe Gln

1 5 10 15

Gly

<210> 1110

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1110

Leu His Tyr Tyr His Ser Glu Glu Phe Asp Val

1 5 10

<210> 1111

<211> 109

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1111

Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly

1 5 10 15

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Ser

20 25 30

Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu

35 40 45

Ile Tyr Gly Gln Ser Ser Arg Thr Arg 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 Gln Gln Phe Gly Asp Asn Gln

85 90 95

Leu Phe Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

100 105

<210> 1112

<211> 12

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1112

Arg Ala Ser Gln Ser Val Ser Ser Ser Tyr Leu Ala

1 5 10

<210> 1113

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1113

Gly Gln Ser Ser Arg Thr Arg

15

<210> 1114

<211> 10

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1114

Gln Gln Phe Gly Asp Asn Gln Leu Phe Thr

1 5 10

<210> 1115

<211> 120

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1115

Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Glu

1 5 10 15

Ser Leu Arg Ile Ser Cys Lys Gly Ser Gly Tyr Ser Phe Ser Thr Ser

20 25 30

Trp Ile Ser Trp Val Arg Gln Met Pro Gly Lys Gly Leu Glu Trp Met

35 40 45

Gly Met Ile Asp Pro Ser Asp Ser Phe Thr Ser Tyr Ser Pro Ser Phe

50 55 60

Gln Gly His Val Thr Ile Ser Ala Asp Lys Ser Ile Ser Thr Ala Tyr

65 70 75 80

Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala Met Tyr Tyr Cys

85 90 95

Ala Arg Leu His Tyr Tyr Asn Ser Glu Glu Phe Asp Val Trp Gly Gln

100 105 110

Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 1116

<211> 5

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1116

Thr Ser Trp Ile Ser

15

<210> 1117

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1117

Met Ile Asp Pro Ser Asp Ser Phe Thr Ser Tyr Ser Pro Ser Phe Gln

1 5 10 15

Gly

<210> 1118

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1118

Leu His Tyr Tyr Asn Ser Glu Glu Phe Asp Val

1 5 10

<210> 1119

<211> 109

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1119

Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly

1 5 10 15

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Ser

20 25 30

Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu

35 40 45

Ile Tyr Gly Gln Ser Ser Arg Thr Arg 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 Gln Gln Phe Gly Asp Asn Gln

85 90 95

Leu Phe Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

100 105

<210> 1120

<211> 12

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1120

Arg Ala Ser Gln Ser Val Ser Ser Ser Tyr Leu Ala

1 5 10

<210> 1121

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1121

Gly Gln Ser Ser Arg Thr Arg

15

<210> 1122

<211> 10

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1122

Gln Gln Phe Gly Asp Asn Gln Leu Phe Thr

1 5 10

<210> 1123

<211> 120

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1123

Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Glu

1 5 10 15

Ser Leu Arg Ile Ser Cys Lys Gly Ser Gly Tyr Ser Phe Ser Thr Ser

20 25 30

Trp Ile Val Trp Val Arg Gln Met Pro Gly Lys Gly Leu Glu Trp Met

35 40 45

Gly Met Ile Asp Pro Ser Asp Ser Tyr Thr Ser Tyr Ser Pro Ser Phe

50 55 60

Gln Gly His Val Thr Ile Ser Ala Asp Lys Ser Ile Ser Thr Ala Tyr

65 70 75 80

Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala Met Tyr Tyr Cys

85 90 95

Ala Arg Leu His Tyr Tyr Asn Ser Glu Glu Phe Asp Val Trp Gly Gln

100 105 110

Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 1124

<211> 5

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1124

Thr Ser Trp Ile Val

15

<210> 1125

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1125

Met Ile Asp Pro Ser Asp Ser Tyr Thr Ser Tyr Ser Pro Ser Phe Gln

1 5 10 15

Gly

<210> 1126

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1126

Leu His Tyr Tyr Asn Ser Glu Glu Phe Asp Val

1 5 10

<210> 1127

<211> 109

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1127

Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly

1 5 10 15

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Ser

20 25 30

Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu

35 40 45

Ile Tyr Gly Gln Ser Ser Arg Thr Arg 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 Gln Gln Phe Gly Asp Asn Gln

85 90 95

Leu Phe Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

100 105

<210> 1128

<211> 12

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1128

Arg Ala Ser Gln Ser Val Ser Ser Ser Tyr Leu Ala

1 5 10

<210> 1129

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1129

Gly Gln Ser Ser Arg Thr Arg

15

<210> 1130

<211> 10

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1130

Gln Gln Phe Gly Asp Asn Gln Leu Phe Thr

1 5 10

<210> 1131

<211> 120

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1131

Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Glu

1 5 10 15

Ser Leu Arg Ile Ser Cys Lys Gly Ser Gly Tyr Ser Phe Ser Thr Ser

20 25 30

Trp Ile Val Trp Val Arg Gln Met Pro Gly Lys Gly Leu Glu Trp Met

35 40 45

Gly Met Ile Asp Pro Ser Asp Ser Tyr Thr Ser Tyr Ser Pro Ser Phe

50 55 60

Gln Gly His Val Thr Ile Ser Ala Asp Lys Ser Ile Ser Thr Ala Tyr

65 70 75 80

Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala Met Tyr Tyr Cys

85 90 95

Ala Arg Leu His Tyr Tyr Asn Ser Glu Glu Phe Asp Val Trp Gly Gln

100 105 110

Gly Thr Met Val Thr Val Ser Ser

115 120

<210> 1132

<211> 5

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1132

Thr Ser Trp Ile Val

15

<210> 1133

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1133

Met Ile Asp Pro Ser Asp Ser Tyr Thr Ser Tyr Ser Pro Ser Phe Gln

1 5 10 15

Gly

<210> 1134

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1134

Leu His Tyr Tyr Asn Ser Glu Glu Phe Asp Val

1 5 10

<210> 1135

<211> 109

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1135

Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly

1 5 10 15

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Ser

20 25 30

Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu

35 40 45

Ile Tyr Gly Gln Ser Ser Arg Thr Arg 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 Gln Gln Phe Gly Asp Asn Gln

85 90 95

Leu Phe Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

100 105

<210> 1136

<211> 12

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1136

Arg Ala Ser Gln Ser Val Ser Ser Ser Tyr Leu Ala

1 5 10

<210> 1137

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1137

Gly Gln Ser Ser Arg Thr Arg

15

<210> 1138

<211> 10

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1138

Gln Gln Phe Gly Asp Asn Gln Leu Phe Thr

1 5 10

<210> 1139

<211> 120

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1139

Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Glu

1 5 10 15

Ser Leu Arg Ile Ser Cys Lys Gly Ser Gly Tyr Ser Phe Ser Thr Ser

20 25 30

Trp Ile Ser Trp Val Arg Gln Met Pro Gly Lys Gly Leu Glu Trp Met

35 40 45

Gly Met Ile Asp Pro Ser Asp Ser Tyr Thr Ser Tyr Ser Pro Ser Phe

50 55 60

Gln Gly His Val Thr Ile Ser Ala Asp Lys Ser Ile Ser Thr Ala Tyr

65 70 75 80

Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala Met Tyr Tyr Cys

85 90 95

Ala Arg Leu His Tyr Tyr Asn Ser Glu Glu Phe Asp Val Trp Gly Gln

100 105 110

Gly Thr Met Val Thr Val Ser Ser

115 120

<210> 1140

<211> 5

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1140

Thr Ser Trp Ile Ser

15

<210> 1141

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1141

Met Ile Asp Pro Ser Asp Ser Tyr Thr Ser Tyr Ser Pro Ser Phe Gln

1 5 10 15

Gly

<210> 1142

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1142

Leu His Tyr Tyr Asn Ser Glu Glu Phe Asp Val

1 5 10

<210> 1143

<211> 109

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1143

Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly

1 5 10 15

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Ser

20 25 30

Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu

35 40 45

Ile Tyr Gly Gln Ser Ser Arg Thr Arg 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 Gln Gln Phe Gly Asp Asp Gln

85 90 95

Leu Phe Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

100 105

<210> 1144

<211> 12

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1144

Arg Ala Ser Gln Ser Val Ser Ser Ser Tyr Leu Ala

1 5 10

<210> 1145

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1145

Gly Gln Ser Ser Arg Thr Arg

15

<210> 1146

<211> 10

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1146

Gln Gln Phe Gly Asp Asp Gln Leu Phe Thr

1 5 10

<210> 1147

<211> 120

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1147

Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Glu

1 5 10 15

Ser Leu Arg Ile Ser Cys Lys Gly Ser Gly Tyr Ser Phe Thr Thr Ser

20 25 30

Trp Ile Ser Trp Val Arg Gln Met Pro Gly Lys Gly Leu Glu Trp Met

35 40 45

Gly Met Ile Asp Pro Ser Asp Ser Phe Thr Ser Tyr Ser Pro Ser Phe

50 55 60

Gln Gly His Val Thr Ile Ser Ala Asp Lys Ser Ile Ser Thr Ala Tyr

65 70 75 80

Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala Met Tyr Tyr Cys

85 90 95

Ala Arg Leu His Tyr Tyr His Ser Glu Glu Phe Asp Val Trp Gly Gln

100 105 110

Gly Thr Met Val Thr Val Ser Ser

115 120

<210> 1148

<211> 5

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1148

Thr Ser Trp Ile Ser

15

<210> 1149

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1149

Met Ile Asp Pro Ser Asp Ser Phe Thr Ser Tyr Ser Pro Ser Phe Gln

1 5 10 15

Gly

<210> 1150

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1150

Leu His Tyr Tyr His Ser Glu Glu Phe Asp Val

1 5 10

<210> 1151

<211> 109

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1151

Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly

1 5 10 15

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Ser

20 25 30

Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu

35 40 45

Ile Tyr Gly Gln Ser Ser Arg Thr Arg 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 Gln Gln Phe Gly Asp Asp Gln

85 90 95

Leu Phe Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

100 105

<210> 1152

<211> 12

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1152

Arg Ala Ser Gln Ser Val Ser Ser Ser Tyr Leu Ala

1 5 10

<210> 1153

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1153

Gly Gln Ser Ser Arg Thr Arg

15

<210> 1154

<211> 10

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1154

Gln Gln Phe Gly Asp Asp Gln Leu Phe Thr

1 5 10

<210> 1155

<211> 120

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1155

Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Glu

1 5 10 15

Ser Leu Arg Ile Ser Cys Lys Gly Ser Gly Tyr Ser Phe Thr Thr Ser

20 25 30

Trp Ile Ser Trp Val Arg Gln Met Pro Gly Lys Gly Leu Glu Trp Met

35 40 45

Gly Met Ile Asp Pro Ser Asp Ser Tyr Thr Ser Tyr Ser Pro Ser Phe

50 55 60

Gln Gly His Val Thr Ile Ser Ala Asp Lys Ser Ile Ser Thr Ala Tyr

65 70 75 80

Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala Met Tyr Tyr Cys

85 90 95

Ala Arg Leu His Tyr Tyr His Ser Glu Glu Phe Asp Val Trp Gly Gln

100 105 110

Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 1156

<211> 5

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1156

Thr Ser Trp Ile Ser

15

<210> 1157

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1157

Met Ile Asp Pro Ser Asp Ser Tyr Thr Ser Tyr Ser Pro Ser Phe Gln

1 5 10 15

Gly

<210> 1158

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1158

Leu His Tyr Tyr His Ser Glu Glu Phe Asp Val

1 5 10

<210> 1159

<211> 109

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1159

Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly

1 5 10 15

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Ser

20 25 30

Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu

35 40 45

Ile Tyr Gly Gln Ser Ser Arg Thr Arg 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 Gln Gln Phe Gly Asp Asp Gln

85 90 95

Leu Phe Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

100 105

<210> 1160

<211> 12

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1160

Arg Ala Ser Gln Ser Val Ser Ser Ser Tyr Leu Ala

1 5 10

<210> 1161

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1161

Gly Gln Ser Ser Arg Thr Arg

15

<210> 1162

<211> 10

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1162

Gln Gln Phe Gly Asp Asp Gln Leu Phe Thr

1 5 10

<210> 1163

<211> 120

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1163

Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Glu

1 5 10 15

Ser Leu Arg Ile Ser Cys Lys Gly Ser Gly Tyr Ser Phe Thr Thr Ser

20 25 30

Trp Ile Ser Trp Val Arg Gln Met Pro Gly Lys Gly Leu Glu Trp Met

35 40 45

Gly Met Ile Asp Pro Ser Asp Ser Tyr Thr Ser Tyr Ser Pro Ser Phe

50 55 60

Gln Gly His Val Thr Ile Ser Ala Asp Lys Ser Ile Ser Thr Ala Tyr

65 70 75 80

Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala Met Tyr Tyr Cys

85 90 95

Ala Arg Leu His Tyr Tyr His Ser Glu Glu Phe Asp Val Trp Gly Gln

100 105 110

Gly Thr Met Val Thr Val Ser Ser

115 120

<210> 1164

<211> 5

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1164

Thr Ser Trp Ile Ser

15

<210> 1165

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1165

Met Ile Asp Pro Ser Asp Ser Tyr Thr Ser Tyr Ser Pro Ser Phe Gln

1 5 10 15

Gly

<210> 1166

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1166

Leu His Tyr Tyr His Ser Glu Glu Phe Asp Val

1 5 10

<210> 1167

<211> 109

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1167

Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly

1 5 10 15

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Ser

20 25 30

Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu

35 40 45

Ile Tyr Gly Gln Ser Ser Arg Thr Arg 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 Gln Gln Phe Gly Asp Asp Gln

85 90 95

Leu Phe Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

100 105

<210> 1168

<211> 12

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1168

Arg Ala Ser Gln Ser Val Ser Ser Ser Tyr Leu Ala

1 5 10

<210> 1169

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1169

Gly Gln Ser Ser Arg Thr Arg

15

<210> 1170

<211> 10

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1170

Gln Gln Phe Gly Asp Asp Gln Leu Phe Thr

1 5 10

<210> 1171

<211> 120

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1171

Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Glu

1 5 10 15

Ser Leu Arg Ile Ser Cys Lys Gly Ser Gly Tyr Ser Phe Ser Thr Ser

20 25 30

Trp Ile Ser Trp Val Arg Gln Met Pro Gly Lys Gly Leu Glu Trp Met

35 40 45

Gly Met Ile Asp Pro Ser Asp Ser Phe Thr Ser Tyr Ser Pro Ser Phe

50 55 60

Gln Gly His Val Thr Ile Ser Ala Asp Lys Ser Ile Ser Thr Ala Tyr

65 70 75 80

Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala Met Tyr Tyr Cys

85 90 95

Ala Arg Leu His Tyr Tyr Asn Ser Glu Glu Phe Asp Val Trp Gly Gln

100 105 110

Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 1172

<211> 5

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1172

Thr Ser Trp Ile Ser

15

<210> 1173

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1173

Met Ile Asp Pro Ser Asp Ser Phe Thr Ser Tyr Ser Pro Ser Phe Gln

1 5 10 15

Gly

<210> 1174

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1174

Leu His Tyr Tyr Asn Ser Glu Glu Phe Asp Val

1 5 10

<210> 1175

<211> 109

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1175

Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly

1 5 10 15

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Ser

20 25 30

Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu

35 40 45

Ile Tyr Gly Gln Ser Ser Arg Thr Arg 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 Gln Gln Phe Gly Asp Asp Gln

85 90 95

Leu Phe Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

100 105

<210> 1176

<211> 12

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1176

Arg Ala Ser Gln Ser Val Ser Ser Ser Tyr Leu Ala

1 5 10

<210> 1177

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1177

Gly Gln Ser Ser Arg Thr Arg

15

<210> 1178

<211> 10

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1178

Gln Gln Phe Gly Asp Asp Gln Leu Phe Thr

1 5 10

<210> 1179

<211> 120

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1179

Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Glu

1 5 10 15

Ser Leu Arg Ile Ser Cys Lys Gly Ser Gly Tyr Ser Phe Ser Thr Ser

20 25 30

Trp Ile Val Trp Val Arg Gln Met Pro Gly Lys Gly Leu Glu Trp Met

35 40 45

Gly Met Ile Asp Pro Ser Asp Ser Tyr Thr Ser Tyr Ser Pro Ser Phe

50 55 60

Gln Gly His Val Thr Ile Ser Ala Asp Lys Ser Ile Ser Thr Ala Tyr

65 70 75 80

Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala Met Tyr Tyr Cys

85 90 95

Ala Arg Leu His Tyr Tyr Asn Ser Glu Glu Phe Asp Val Trp Gly Gln

100 105 110

Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 1180

<211> 5

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1180

Thr Ser Trp Ile Val

15

<210> 1181

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1181

Met Ile Asp Pro Ser Asp Ser Tyr Thr Ser Tyr Ser Pro Ser Phe Gln

1 5 10 15

Gly

<210> 1182

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1182

Leu His Tyr Tyr Asn Ser Glu Glu Phe Asp Val

1 5 10

<210> 1183

<211> 109

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1183

Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly

1 5 10 15

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Ser

20 25 30

Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu

35 40 45

Ile Tyr Gly Gln Ser Ser Arg Thr Arg 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 Gln Gln Phe Gly Asp Asp Gln

85 90 95

Leu Phe Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

100 105

<210> 1184

<211> 12

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1184

Arg Ala Ser Gln Ser Val Ser Ser Ser Tyr Leu Ala

1 5 10

<210> 1185

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1185

Gly Gln Ser Ser Arg Thr Arg

15

<210> 1186

<211> 10

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1186

Gln Gln Phe Gly Asp Asp Gln Leu Phe Thr

1 5 10

<210> 1187

<211> 120

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1187

Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Glu

1 5 10 15

Ser Leu Arg Ile Ser Cys Lys Gly Ser Gly Tyr Ser Phe Ser Thr Ser

20 25 30

Trp Ile Val Trp Val Arg Gln Met Pro Gly Lys Gly Leu Glu Trp Met

35 40 45

Gly Met Ile Asp Pro Ser Asp Ser Tyr Thr Ser Tyr Ser Pro Ser Phe

50 55 60

Gln Gly His Val Thr Ile Ser Ala Asp Lys Ser Ile Ser Thr Ala Tyr

65 70 75 80

Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala Met Tyr Tyr Cys

85 90 95

Ala Arg Leu His Tyr Tyr Asn Ser Glu Glu Phe Asp Val Trp Gly Gln

100 105 110

Gly Thr Met Val Thr Val Ser Ser

115 120

<210> 1188

<211> 5

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1188

Thr Ser Trp Ile Val

15

<210> 1189

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1189

Met Ile Asp Pro Ser Asp Ser Tyr Thr Ser Tyr Ser Pro Ser Phe Gln

1 5 10 15

Gly

<210> 1190

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1190

Leu His Tyr Tyr Asn Ser Glu Glu Phe Asp Val

1 5 10

<210> 1191

<211> 109

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1191

Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly

1 5 10 15

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Ser

20 25 30

Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu

35 40 45

Ile Tyr Gly Gln Ser Ser Arg Thr Arg 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 Gln Gln Phe Gly Asp Asp Gln

85 90 95

Leu Phe Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

100 105

<210> 1192

<211> 12

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1192

Arg Ala Ser Gln Ser Val Ser Ser Ser Tyr Leu Ala

1 5 10

<210> 1193

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1193

Gly Gln Ser Ser Arg Thr Arg

15

<210> 1194

<211> 10

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1194

Gln Gln Phe Gly Asp Asp Gln Leu Phe Thr

1 5 10

<210> 1195

<211> 326

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1195

Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Cys Ser Arg

1 5 10 15

Ser Thr Ser Glu Ser Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr

20 25 30

Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser

35 40 45

Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser

50 55 60

Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Lys Thr

65 70 75 80

Tyr Thr Cys Asn Val Asp His Lys Pro Ser Asn Thr Lys Val Asp Lys

85 90 95

Arg Val Glu Ser Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro

100 105 110

Glu Phe Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys

115 120 125

Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val

130 135 140

Asp Val Ser Gln Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp

145 150 155 160

Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe

165 170 175

Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp

180 185 190

Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu

195 200 205

Pro Ser Ser Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg

210 215 220

Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Gln Glu Glu Met Thr Lys

225 230 235 240

Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp

245 250 255

Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys

260 265 270

Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser

275 280 285

Arg Leu Thr Val Asp Lys Ser Arg Trp Gln Glu Gly Asn Val Phe Ser

290 295 300

Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser

305 310 315 320

Leu Ser Leu Ser Leu Gly

325

<210> 1196

<211> 326

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1196

Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Cys Ser Arg

1 5 10 15

Ser Thr Ser Glu Ser Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr

20 25 30

Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser

35 40 45

Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser

50 55 60

Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Lys Thr

65 70 75 80

Tyr Thr Cys Asn Val Asp His Lys Pro Ser Asn Thr Lys Val Asp Lys

85 90 95

Arg Val Glu Ser Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro

100 105 110

Glu Phe Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys

115 120 125

Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val

130 135 140

Asp Val Ser Gln Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp

145 150 155 160

Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe

165 170 175

Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp

180 185 190

Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu

195 200 205

Pro Ser Ser Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg

210 215 220

Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Gln Glu Glu Met Thr Lys

225 230 235 240

Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp

245 250 255

Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys

260 265 270

Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Leu Leu Tyr Ser

275 280 285

Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Glu Gly Asn Val Phe Ser

290 295 300

Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser

305 310 315 320

Leu Ser Leu Ser Leu Gly

325

<210> 1197

<211> 107

<212> PROTEIN

<213> Homo sapiens

<400> 1197

Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu

1 5 10 15

Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe

20 25 30

Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln

35 40 45

Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser

50 55 60

Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu

65 70 75 80

Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser

85 90 95

Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys

100 105

<210> 1198

<211> 329

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1198

Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys

1 5 10 15

Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr

20 25 30

Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser

35 40 45

Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser

50 55 60

Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr

65 70 75 80

Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys

85 90 95

Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys

100 105 110

Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro

115 120 125

Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys

130 135 140

Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp

145 150 155 160

Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu

165 170 175

Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu

180 185 190

His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn

195 200 205

Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly

210 215 220

Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu

225 230 235 240

Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr

245 250 255

Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn

260 265 270

Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Leu

275 280 285

Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn

290 295 300

Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr

305 310 315 320

Gln Lys Ser Leu Ser Leu Ser Pro Gly

325

<210> 1199

<211> 329

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1199

Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys

1 5 10 15

Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr

20 25 30

Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser

35 40 45

Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser

50 55 60

Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr

65 70 75 80

Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys

85 90 95

Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys

100 105 110

Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro

115 120 125

Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys

130 135 140

Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp

145 150 155 160

Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu

165 170 175

Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu

180 185 190

His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn

195 200 205

Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly

210 215 220

Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu

225 230 235 240

Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr

245 250 255

Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn

260 265 270

Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe

275 280 285

Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn

290 295 300

Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr

305 310 315 320

Gln Lys Ser Leu Ser Leu Ser Pro Gly

325

<210> 1200

<211> 6

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1200

His His His His His

15

<210> 1201

<211> 10

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1201

Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser

1 5 10

<210> 1202

<211> 122

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1202

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Arg

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe His Asp Tyr

20 25 30

Ala Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Gly Ile Ser Trp Lys Gly Asp Ile Gly Gly 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 Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Leu Tyr Tyr Cys

85 90 95

Ala Lys Ser Tyr Gly Ser Gly Ser Phe Tyr Asn Ala Phe Asp Ser Trp

100 105 110

Gly Gln Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 1203

<211> 5

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1203

Asp Tyr Ala Met His

15

<210> 1204

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1204

Gly Ile Ser Trp Lys Gly Asp Ile Gly Gly Tyr Val Asp Ser Val Lys

1 5 10 15

Gly

<210> 1205

<211> 13

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1205

Ser Tyr Gly Ser Gly Ser Phe Tyr Asn Ala Phe Asp Ser

1 5 10

<210> 1206

<211> 107

<212> PROTEIN

<213> Homo sapiens

<400> 1206

Asp Ile Gln Met Thr Gln Ser Pro Ser Thr Leu Ser Ala Ser Val Gly

1 5 10 15

Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Ser Trp

20 25 30

Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Phe Leu Ile

35 40 45

Tyr Lys Ala Ser Lys Leu Asp Arg Gly Thr Pro Ser Arg Phe Ser Gly

50 55 60

Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro

65 70 75 80

Asp Asp Phe Ala Thr Tyr Tyr Cys Leu Glu Tyr Ser Ser Tyr Ile Arg

85 90 95

Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys

100 105

<210> 1207

<211> 11

<212> PROTEIN

<213> Homo sapiens

<400> 1207

Arg Ala Ser Gln Ser Ile Ser Ser Trp Leu Ala

1 5 10

<210> 1208

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1208

Lys Ala Ser Lys Leu Asp Arg

15

<210> 1209

<211> 9

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1209

Leu Glu Tyr Ser Ser Tyr Ile Arg Thr

15

<210> 1210

<211> 122

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1210

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Arg

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe His Asp Tyr

20 25 30

Ala Met His Trp Val Arg Gln Val Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Gly Ile Ser Trp Arg Gly Asp Ile Gly Gly Tyr Val Lys 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 Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Leu Tyr Tyr Cys

85 90 95

Val Lys Ser Tyr Gly Ser Gly Ser Phe Tyr Asn Ala Phe Asp Ser Trp

100 105 110

Gly Gln Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 1211

<211> 5

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1211

Asp Tyr Ala Met His

15

<210> 1212

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1212

Gly Ile Ser Trp Arg Gly Asp Ile Gly Gly Tyr Val Lys Ser Val Lys

1 5 10 15

Gly

<210> 1213

<211> 13

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1213

Ser Tyr Gly Ser Gly Ser Phe Tyr Asn Ala Phe Asp Ser

1 5 10

<210> 1214

<211> 107

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1214

Asp Ile Gln Met Thr Gln Ser Pro Ser Thr Leu Ser Ala Ser Val Gly

1 5 10 15

Asp Glu Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Ser Trp

20 25 30

Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Phe Leu Ile

35 40 45

Tyr Lys Ala Ser Lys Leu Glu Arg Gly Thr Pro Ser Arg Phe Ser Gly

50 55 60

Ser Gly Ser Gly Thr Glu Phe Ser Leu Thr Ile Ser Ser Leu Gln Pro

65 70 75 80

Asp Asp Phe Ala Thr Tyr Tyr Cys Leu Glu Tyr Ser Ser Tyr Ile Arg

85 90 95

Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys

100 105

<210> 1215

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1215

Arg Ala Ser Gln Ser Ile Ser Ser Trp Leu Ala

1 5 10

<210> 1216

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1216

Lys Ala Ser Lys Leu Glu Arg

15

<210> 1217

<211> 9

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1217

Leu Glu Tyr Ser Ser Tyr Ile Arg Thr

15

<210> 1218

<211> 122

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1218

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Arg

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe His Asp Tyr

20 25 30

Ala Met His Trp Val Arg Gln Val Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Gly Ile Ser Trp Arg Gly Asp Ile Gly Gly Tyr Ala Lys 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 Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Leu Tyr Tyr Cys

85 90 95

Val Lys Ser Tyr Gly Ser Gly Ser Phe Tyr Asn Ala Phe Asp Ser Trp

100 105 110

Gly Gln Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 1219

<211> 5

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1219

Asp Tyr Ala Met His

15

<210> 1220

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1220

Gly Ile Ser Trp Arg Gly Asp Ile Gly Gly Tyr Ala Lys Ser Val Lys

1 5 10 15

Gly

<210> 1221

<211> 13

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1221

Ser Tyr Gly Ser Gly Ser Phe Tyr Asn Ala Phe Asp Ser

1 5 10

<210> 1222

<211> 107

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1222

Asp Ile Gln Met Thr Gln Ser Pro Ser Thr Leu Ser Ala Ser Val Gly

1 5 10 15

Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Ser Trp

20 25 30

Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Phe Leu Ile

35 40 45

Tyr Lys Ala Ser Lys Leu Asp Arg Gly Thr Pro Ser Arg Phe Ser Gly

50 55 60

Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro

65 70 75 80

Asp Asp Phe Ala Thr Tyr Tyr Cys Leu Glu Tyr Ser Ser Tyr Ile Arg

85 90 95

Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys

100 105

<210> 1223

<211> 11

<212> PROTEIN

<213> Homo sapiens

<400> 1223

Arg Ala Ser Gln Ser Ile Ser Ser Trp Leu Ala

1 5 10

<210> 1224

<211> 7

<212> PROTEIN

<213> Homo sapiens

<400> 1224

Lys Ala Ser Lys Leu Asp Arg

15

<210> 1225

<211> 9

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1225

Leu Glu Tyr Ser Ser Tyr Ile Arg Thr

15

<210> 1226

<211> 122

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1226

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Arg

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asp Asp Tyr

20 25 30

Ala Met His Trp Val Arg Gln Val Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Gly Ile Ser Trp Arg Gly Asp Ile Gly Gly Tyr Val Lys 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 Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Leu Tyr Tyr Cys

85 90 95

Val Lys Ser Tyr Gly Ser Gly Ser Phe Tyr Asn Ala Phe Asp Ser Trp

100 105 110

Gly Gln Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 1227

<211> 5

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1227

Asp Tyr Ala Met His

15

<210> 1228

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1228

Gly Ile Ser Trp Arg Gly Asp Ile Gly Gly Tyr Val Lys Ser Val Lys

1 5 10 15

Gly

<210> 1229

<211> 13

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1229

Ser Tyr Gly Ser Gly Ser Phe Tyr Asn Ala Phe Asp Ser

1 5 10

<210> 1230

<211> 107

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1230

Asp Ile Gln Met Thr Gln Ser Pro Ser Thr Leu Ser Ala Ser Val Gly

1 5 10 15

Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Ser Trp

20 25 30

Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Phe Leu Ile

35 40 45

Tyr Lys Ala Ser Lys Leu Asp Arg Gly Thr Pro Ser Arg Phe Ser Gly

50 55 60

Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro

65 70 75 80

Asp Asp Phe Ala Thr Tyr Tyr Cys Leu Glu Tyr Ser Ser Tyr Ile Arg

85 90 95

Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys

100 105

<210> 1231

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1231

Arg Ala Ser Gln Ser Ile Ser Ser Trp Leu Ala

1 5 10

<210> 1232

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1232

Lys Ala Ser Lys Leu Asp Arg

15

<210> 1233

<211> 9

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1233

Leu Glu Tyr Ser Ser Tyr Ile Arg Thr

15

<210> 1234

<211> 122

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1234

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Arg

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asp Asp Tyr

20 25 30

Ala Met His Trp Val Arg Gln Val Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Gly Ile Ser Trp Arg Gly Asp Ile Gly Gly Tyr Val Lys 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 Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Leu Tyr Tyr Cys

85 90 95

Val Lys Ser Tyr Gly Ser Gly Ser Phe Tyr Asn Ala Phe Asp Ser Trp

100 105 110

Gly Gln Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 1235

<211> 5

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1235

Asp Tyr Ala Met His

15

<210> 1236

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1236

Gly Ile Ser Trp Arg Gly Asp Ile Gly Gly Tyr Val Lys Ser Val Lys

1 5 10 15

Gly

<210> 1237

<211> 13

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1237

Ser Tyr Gly Ser Gly Ser Phe Tyr Asn Ala Phe Asp Ser

1 5 10

<210> 1238

<211> 107

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1238

Asp Ile Gln Met Thr Gln Ser Pro Ser Thr Leu Ser Ala Ser Val Gly

1 5 10 15

Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Ser Trp

20 25 30

Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile

35 40 45

Tyr Lys Ala Ser Lys Leu Asp Arg Gly Thr Pro Ser Arg Phe Ser Gly

50 55 60

Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro

65 70 75 80

Asp Asp Phe Ala Thr Tyr Tyr Cys Leu Glu Tyr Ser Ser Tyr Ile Arg

85 90 95

Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys

100 105

<210> 1239

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1239

Arg Ala Ser Gln Ser Ile Ser Ser Trp Leu Ala

1 5 10

<210> 1240

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1240

Lys Ala Ser Lys Leu Asp Arg

15

<210> 1241

<211> 9

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1241

Leu Glu Tyr Ser Ser Tyr Ile Arg Thr

15

<210> 1242

<211> 122

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1242

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Arg

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe His Asp Tyr

20 25 30

Ala Met His Trp Val Arg Gln Val Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Gly Ile Ser Trp Arg Gly Asp Ile Gly Gly Tyr Val Lys 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 Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Leu Tyr Tyr Cys

85 90 95

Val Lys Ser Tyr Gly Ser Gly Ser Phe Tyr Asn Ala Phe Asp Ser Trp

100 105 110

Gly Gln Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 1243

<211> 5

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1243

Asp Tyr Ala Met His

15

<210> 1244

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1244

Gly Ile Ser Trp Arg Gly Asp Ile Gly Gly Tyr Val Lys Ser Val Lys

1 5 10 15

Gly

<210> 1245

<211> 13

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1245

Ser Tyr Gly Ser Gly Ser Phe Tyr Asn Ala Phe Asp Ser

1 5 10

<210> 1246

<211> 107

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1246

Asp Ile Gln Met Thr Gln Ser Pro Ser Thr Leu Ser Ala Ser Val Gly

1 5 10 15

Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Ser Trp

20 25 30

Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Phe Leu Ile

35 40 45

Tyr Lys Ala Ser Lys Leu Asp Arg Gly Thr Pro Ser Arg Phe Ser Gly

50 55 60

Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro

65 70 75 80

Asp Asp Phe Ala Thr Tyr Tyr Cys Leu Glu Tyr Ser Ser Tyr Ile Arg

85 90 95

Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys

100 105

<210> 1247

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1247

Arg Ala Ser Gln Ser Ile Ser Ser Trp Leu Ala

1 5 10

<210> 1248

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1248

Lys Ala Ser Lys Leu Asp Arg

15

<210> 1249

<211> 9

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Recombinant protein

<400> 1249

Leu Glu Tyr Ser Ser Tyr Ile Arg Thr

15

<---

Claims (133)

1. A bispecific antibody or an antigen-binding fragment thereof, stimulating the enzymatic activity of FIXa against FX, containing a first antigen-binding site and a second antigen-binding site, where said first antigen-binding region binds to an epitope containing amino acid residues R338, T340, K341 according to SEQ ID NO: 1, and wherein the second antigen-binding region binds to an epitope containing amino acid residues: i) E103, Q104, V108, R113, T116, L117, D119, I125, T127, E228, F229, Y230, E266, R287, P291, I292, P304, L419, K420, D423, R424, M426, K427 and T428 from FX(a) according to SEQ ID NO: 2 or ii) E103, Q104, V108, R113, T116, L117, A118, D119, I125, T127, S227, E228, Y230, R287, I292, L303, P304, L419, K420, D423, R424, M426, K427 and T428 from FX(a) according to SEQ ID NO: 2. 2. The antibody or antigen binding fragment thereof according to claim 1, wherein the first antigen binding region binds to an epitope comprising L337, R338, S339, T340 and K341 of FIX(a) according to SEQ ID NO: 1, and wherein the second antigen binding region binds to the epitope containing amino acid residues: i) E103, Q104, V108, R113, T116, L117, D119, I125, T127, E228, F229, Y230, E266, R287, P291, I292, P304, L419, K420, D423, R424, M426, K427 and T428 from FX(a) according to SEQ ID NO: 2 or ii) E103, Q104, V108, R113, T116, L117, A118, D119, I125, T127, S227, E228, Y230, R287, I292, L303, P304, L419, K420, D423, R424, M426, K427 and T428 from FX(a) according to SEQ ID NO: 2. 3. An antibody or an antigen-binding fragment thereof according to claim 1, where the first antigen-binding site contains: i) a paratope containing amino acid residues D30, D31, W53, S102, S104 and N107 in the heavy chain variable domain (SEQ ID NO: 35) and amino acid residues Y91 and S92 in the light chain variable domain (SEQ ID NO: 39), or ii) a paratope containing amino acid residues H30, D31, W53, D56, S102, S104, Y106 and N107 in the heavy chain variable domain (SEQ ID NO: 67) and amino acid residues Y91 and S92 in the light chain variable domain (SEQ ID NO: 71), or iii) a paratope containing amino acid residues H30, D31, W53, S102, S104, Y106 and N107 in the heavy chain variable domain (SEQ ID NO: 51) and amino acid residues Y91 and S92 in the light chain variable domain (SEQ ID NO: 55) , and the second antigen binding region comprises: a) a paratope containing amino acid residues K23, G24, S25, G26, Y27, W33, D52, S54, D55, Y57, S77, L99, H100, Y101, Y102, N103 and S104 in the heavy chain variable domain (SEQ ID NO: 483) and amino acid residues S30, S31, Y33, Y50, Q52, S54, R55, R57, Y92 and D94 in the light chain variable domain (SEQ ID NO: 487), or b) a paratope containing amino acid residues K23, S25, G26, Y27, F29, W33, D52, S54, D55, F57, S77, H100, Y101, Y102, N103 and S104 in the heavy chain variable domain (SEQ ID NO: 467) and residues V29, S30, S31, Y33, Y50, Q52, S54, R55, R57 and D94 in the light chain variable domain (SEQ ID NO: 471). 4. A bispecific antibody or antigen-binding fragment thereof that binds to FIX (SEQ ID NO: 1) and/or its activated form (FIXa) and binds to FX (SEQ ID NO: 2) and/or its activated form (FXa), where said bispecific antibody contains an anti-FIX(a) antibody or an antigen-binding fragment thereof, comprising a heavy chain and a light chain, and an antibody to FX(a) or an antigen-binding fragment thereof, containing a heavy chain and a light chain, Where: a) the anti-FIX(a) antibody heavy chain CDR1-3 sequences are identified as SEQ ID NOs: 36, 37 and 38, respectively, and the light chain CDR1-3 sequences of the anti-FIX(a) antibody are identified at SEQ ID NO: 40, 41 and 42, respectively, and the anti-FX(a) antibody heavy chain CDR1-3 sequences are identified as SEQ ID NOs: 468, 469 and 470, respectively, and the anti-FX(a) antibody light chain CDR1-3 sequences are identified by SEQ ID NOs: 472, 473 and 474, respectively, or b) the anti-FIX(a) antibody heavy chain CDR1-3 sequences are identified as SEQ ID NOs: 36, 37 and 38, respectively, and the light chain CDR1-3 sequences of the anti-FIX(a) antibody are identified at SEQ ID NO: 40, 41 and 42, respectively, and the anti-FX(a) antibody heavy chain CDR1-3 sequences are identified as SEQ ID NOs: 484, 485 and 486, respectively, and the anti-FX(a) antibody light chain CDR1-3 sequences are identified by SEQ ID NO: 488, 489 and 490, respectively, or c) the anti-FIX(a) antibody heavy chain CDR1-3 sequences are identified as SEQ ID NOs: 44, 45 and 46, respectively, and the light chain CDR1-3 sequences of the anti-FIX(a) antibody are identified as SEQ ID NOs: 48, 49 and 50, respectively, and the anti-FX(a) antibody heavy chain CDR1-3 sequences are identified as SEQ ID NOs: 468, 469 and 470, respectively, and the anti-FX(a) antibody light chain CDR1-3 sequences are identified by SEQ ID NOs: 472, 473 and 474, respectively, or d) the anti-FIX(a) antibody heavy chain CDR1-3 sequences are identified as SEQ ID NOs: 52, 53 and 54, respectively, and the light chain CDR1-3 sequences of the anti-FIX(a) antibody are identified as SEQ ID NOs: 56, 57 and 58, respectively, and the anti-FX(a) antibody heavy chain CDR1-3 sequences are identified as SEQ ID NOs: 468, 469 and 470, respectively, and the anti-FX(a) antibody light chain CDR1-3 sequences are identified by SEQ ID NOs: 472, 473 and 474, respectively, or e) the anti-FIX(a) antibody heavy chain CDR1-3 sequences are identified as SEQ ID NOs: 52, 53 and 54, respectively, and the light chain CDR1-3 sequences of the anti-FIX(a) antibody are identified as SEQ ID NOs: 56, 57 and 58, respectively, and the anti-FX(a) antibody heavy chain CDR1-3 sequences are identified as SEQ ID NOs: 484, 485 and 486, respectively, and the anti-FX(a) antibody light chain CDR1-3 sequences are identified by SEQ ID NO: 488, 489 and 490, respectively, or f) the anti-FIX(a) antibody heavy chain CDR1-3 sequences are identified as SEQ ID NOs: 68, 69 and 70, respectively, and the light chain CDR1-3 sequences of the anti-FIX(a) antibody are identified as SEQ ID NOs: 72, 73 and 74, respectively, and the anti-FX(a) antibody heavy chain CDR1-3 sequences are identified as SEQ ID NOs: 468, 469 and 470, respectively, and the anti-FX(a) antibody light chain CDR1-3 sequences are identified by SEQ ID NOs: 472, 473 and 474, respectively, or g) the anti-FIX(a) antibody heavy chain CDR1-3 sequences are identified as SEQ ID NOs: 68, 69 and 70, respectively, and the light chain CDR1-3 sequences of the anti-FIX(a) antibody are identified as SEQ ID NOs: 72, 73 and 74, respectively, and the anti-FX(a) antibody heavy chain CDR1-3 sequences are identified as SEQ ID NOs: 484, 485 and 486, respectively, and the anti-FX(a) antibody light chain CDR1-3 sequences are identified by SEQ ID NO: 488, 489 and 490, respectively, or h) the anti-FIX(a) antibody heavy chain CDR1-3 sequences are identified as SEQ ID NOs: 1203, 1204 and 1205, respectively, and the anti-FIX(a) antibody light chain CDR1-3 sequences are identified as SEQ ID NOs: 1207, 1208 and 1209, respectively, and the anti-FX(a) antibody heavy chain CDR1-3 sequences are identified as SEQ ID NOs: 468, 469 and 470, respectively, and the anti-FX(a) antibody light chain CDR1-3 sequences are identified by SEQ ID NOs: 472, 473 and 474, respectively, or i) the anti-FIX(a) antibody heavy chain CDR1-3 sequences are identified as SEQ ID NOs: 1211, 1212 and 1213, respectively, and the light chain CDR1-3 sequences of the anti-FIX(a) antibody are identified as SEQ ID NOs: 1215, 1216 and 1217, respectively, and the anti-FX(a) antibody heavy chain CDR1-3 sequences are identified as SEQ ID NOs: 468, 469 and 470, respectively, and the anti-FX(a) antibody light chain CDR1-3 sequences are identified by SEQ ID NOs: 472, 473 and 474, respectively, or j) the anti-FIX(a) antibody heavy chain CDR1-3 sequences are identified as SEQ ID NOs: 1219, 1220 and 1221, respectively, and the light chain CDR1-3 sequences of the anti-FIX(a) antibody are identified as SEQ ID NOs: 1223, 1224 and 1225, respectively, and the anti-FX(a) antibody heavy chain CDR1-3 sequences are identified as SEQ ID NOs: 468, 469 and 470, respectively, and the anti-FX(a) antibody light chain CDR1-3 sequences are identified by SEQ ID NOs: 472, 473 and 474, respectively, or k) the anti-FIX(a) antibody heavy chain CDR1-3 sequences are identified as SEQ ID NOs: 1227, 1228 and 1229, respectively, and the light chain CDR1-3 sequences of the anti-FIX(a) antibody are identified as SEQ ID NOs: 1231, 1232 and 1233, respectively, and the anti-FX(a) antibody heavy chain CDR1-3 sequences are identified as SEQ ID NOs: 468, 469 and 470, respectively, and the anti-FX(a) antibody light chain CDR1-3 sequences are identified by SEQ ID NOs: 472, 473 and 474, respectively, or l) the anti-FIX(a) antibody heavy chain CDR1-3 sequences are identified as SEQ ID NOs: 1235, 1236 and 1237, respectively, and the light chain CDR1-3 sequences of the anti-FIX(a) antibody are identified as SEQ ID NOs: 1239, 1240 and 1241, respectively, and the anti-FX(a) antibody heavy chain CDR1-3 sequences are identified as SEQ ID NOs: 468, 469 and 470, respectively, and the anti-FX(a) antibody light chain CDR1-3 sequences are identified by SEQ ID NOs: 472, 473 and 474, respectively, or m) the anti-FIX(a) antibody heavy chain CDR1-3 sequences are identified as SEQ ID NOs: 1243, 1244 and 1245, respectively, and the light chain CDR1-3 sequences of the anti-FIX(a) antibody are identified as SEQ ID NOs: 1247, 1248 and 1249, respectively, and the anti-FX(a) antibody heavy chain CDR1-3 sequences are identified as SEQ ID NOs: 468, 469 and 470, respectively, and the light chain CDR1-3 sequences of the anti-FX(a) antibody are identified as SEQ ID NOs: 472, 473 and 474, respectively. 5. Antibody or antigen-binding fragment thereof according to claim 4, where the anti-FIX(a) antibody heavy chain CDR1-3 sequences are identified at SEQ ID NOs: 52, 53 and 54, respectively, and the anti-FIX(a) antibody light chain CDR1-3 sequences are identified at SEQ ID NOs: 56, 57 and 58, respectively And the anti-FX(a) antibody heavy chain CDR1-3 sequences are identified at SEQ ID NOs: 468, 469 and 470, respectively, and the anti-FX(a) antibody light chain CDR1-3 sequences are identified at SEQ ID NOs: 472, 473 and 474, respectively . 6. The antibody or antigen-binding fragment thereof according to claim 4, wherein the anti-FIX(a) antibody or antigen-binding fragment thereof comprises a) a heavy chain variable domain identified under SEQ ID NO: 35 and a light chain variable domain identified under SEQ ID NO: 39, or b) the heavy chain variable domain identified by SEQ ID NO: 43 and the light chain variable domain identified by SEQ ID NO: 47, or c) the heavy chain variable domain identified by SEQ ID NO: 51 and the light chain variable domain identified by SEQ ID NO: 55, or d) the heavy chain variable domain identified under SEQ ID NO: 67 and the light chain variable domain identified under SEQ ID NO: 71, or e) the heavy chain variable domain identified under SEQ ID NO: 1202 and the light chain variable domain identified under SEQ ID NO: 1206, or f) the heavy chain variable domain identified by SEQ ID NO: 1210 and the light chain variable domain identified by SEQ ID NO: 1214, or g) the heavy chain variable domain identified under SEQ ID NO: 1218 and the light chain variable domain identified under SEQ ID NO: 1222, or h) the heavy chain variable domain identified under SEQ ID NO: 1226 and the light chain variable domain identified under SEQ ID NO: 1230, or i) the heavy chain variable domain identified under SEQ ID NO: 1234 and the light chain variable domain identified under SEQ ID NO: 1238, or j) the heavy chain variable domain identified under SEQ ID NO: 1242, and the light chain variable domain identified under SEQ ID NO: 1246, and wherein the anti-FX(a) antibody or antigen-binding fragment thereof comprises k) a heavy chain variable domain identified under SEQ ID NO: 467 and a light chain variable domain identified under SEQ ID NO: 471, or l) a heavy chain variable domain identified under SEQ ID NO: 483 and a light chain variable domain identified under SEQ ID NO: 487. 7. The antibody or antigen binding fragment thereof according to claim 6, wherein the anti-FIX(a) antibody or antigen binding fragment thereof comprises a heavy chain variable domain identified under SEQ ID NO: 51 and a light chain variable domain identified under SEQ ID NO: 55 and wherein the anti-FX(a) antibody or antigen binding fragment thereof comprises a heavy chain variable domain identified under SEQ ID NO: 467 and a light chain variable domain identified under SEQ ID NO: 471. 8. An antibody or antigen-binding fragment thereof as claimed in any one of the preceding claims, wherein the isotype of said antibody or antigen-binding fragment thereof is IgG1 or IgG4. 9. The antibody or antigen-binding fragment thereof as claimed in any one of the preceding claims, wherein said antibody or antigen-binding fragment thereof is a procoagulant antibody or antigen-binding fragment thereof. 10. Antibody or antigen-binding fragment thereof according to any one of paragraphs. 4-9, wherein said antibody or antigen-binding fragment stimulates the enzymatic activity of FIXa. 11. Antibody or antigen-binding fragment thereof according to any one of paragraphs. 1-10 for use in the treatment of coagulopathy or bleeding disorders. 12. Antibody or antigen-binding fragment thereof according to any one of paragraphs. 1-10 for use in the treatment of hemophilia A with or without inhibitors. 13. Pharmaceutical composition having procoagulant activity, containing an antibody or an antigen-binding fragment according to any one of paragraphs. 1-10 and one or more pharmaceutically acceptable carriers. 14. Composition according to claim 13 for use in the treatment of coagulopathy or bleeding disorders. 15. Composition according to claim 13 for use in the treatment of hemophilia A with or without the presence of inhibitors. 16. A kit for the treatment of coagulopathy or bleeding disorders, containing (i) an antibody or an antigen-binding fragment according to any one of paragraphs. 1-10 or the composition according to paragraph 13 and (ii) instructions for use. 17. An antibody or antigen-binding fragment thereof that binds to FIX (SEQ ID NO: 1) and/or its activated form (FIXa), containing a heavy chain and a light chain, where: a) the heavy chain CDR1-3 sequences are identified under SEQ ID NO: 36, 37 and 38, respectively; and the light chain CDR1-3 sequences are identified by SEQ ID NO: 40, 41 and 42, respectively, or b) the heavy chain CDR1-3 sequences are identified under SEQ ID NO: 44, 45 and 46, respectively; and the light chain CDR1-3 sequences are identified by SEQ ID NO: 48, 49 and 50, respectively, or c) the heavy chain CDR1-3 sequences are identified under SEQ ID NO: 52, 53 and 54, respectively; and the light chain CDR1-3 sequences are identified by SEQ ID NO: 56, 57 and 58, respectively, or d) the heavy chain CDR1-3 sequences are identified under SEQ ID NO: 68, 69 and 70, respectively; and the light chain CDR1-3 sequences are identified by SEQ ID NO: 72, 73 and 74, respectively, or e) the heavy chain CDR1-3 sequences are identified under SEQ ID NO: 1203, 1204 and 1205, respectively; and the light chain CDR1-3 sequences are identified by SEQ ID NO: 1207, 1208 and 1209, respectively, or f) the heavy chain CDR1-3 sequences are identified under SEQ ID NO: 1211, 1212 and 1213, respectively; and the light chain CDR1-3 sequences are identified under SEQ ID NO: 1215, 1216 and 1217, respectively, or g) the heavy chain CDR1-3 sequences are identified under SEQ ID NO: 1219, 1220 and 1221, respectively; and the light chain CDR1-3 sequences are identified by SEQ ID NO: 1223, 1224 and 1225, respectively, or h) the heavy chain CDR1-3 sequences are identified under SEQ ID NO: 1227, 1228 and 1229, respectively; and the light chain CDR1-3 sequences are identified under SEQ ID NO: 1231, 1232 and 1233, respectively, or i) the heavy chain CDR1-3 sequences are identified under SEQ ID NO: 1235, 1236 and 1237, respectively; and the light chain CDR1-3 sequences are identified by SEQ ID NO: 1239, 1240 and 1241, respectively, or j) the heavy chain CDR1-3 sequences are identified under SEQ ID NO: 1243, 1244 and 1245, respectively; and the light chain CDR1-3 sequences are identified under SEQ ID NO: 1247, 1248 and 1249, respectively, wherein said antibody or antigen-binding fragment thereof is an intermediate in the manufacture of a bispecific antibody that binds to FIX and/or its activated form (FIXa) and binds to FX (SEQ ID NO: 2) and/or its activated form (FXa). 18. An antibody or an antigen-binding fragment thereof according to claim 17, wherein the antibody or an antigen-binding fragment thereof comprises a) a heavy chain variable domain identified under SEQ ID NO: 35 and a light chain variable domain identified under SEQ ID NO: 39, or b) the heavy chain variable domain identified by SEQ ID NO: 43 and the light chain variable domain identified by SEQ ID NO: 47, or c) the heavy chain variable domain identified by SEQ ID NO: 51 and the light chain variable domain identified by SEQ ID NO: 55, or d) the heavy chain variable domain identified under SEQ ID NO: 67 and the light chain variable domain identified under SEQ ID NO: 71, or e) the heavy chain variable domain identified under SEQ ID NO: 1202 and the light chain variable domain identified under SEQ ID NO: 1206, or f) the heavy chain variable domain identified by SEQ ID NO: 1210 and the light chain variable domain identified by SEQ ID NO: 1214, or g) the heavy chain variable domain identified under SEQ ID NO: 1218 and the light chain variable domain identified under SEQ ID NO: 1222, or h) the heavy chain variable domain identified under SEQ ID NO: 1226 and the light chain variable domain identified under SEQ ID NO: 1230, or i) the heavy chain variable domain identified under SEQ ID NO: 1234 and the light chain variable domain identified under SEQ ID NO: 1238, or j) a heavy chain variable domain identified under SEQ ID NO: 1242 and a light chain variable domain identified under SEQ ID NO: 1246. 19. The antibody or antigen-binding fragment thereof of claim 18, wherein the antibody or antigen-binding fragment thereof comprises a heavy chain variable domain identified under SEQ ID NO: 51 and a light chain variable domain identified under SEQ ID NO: 55.

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