CA3211803A1

CA3211803A1 - Antibody fusion proteins targeting il-6 receptor and angiogenic factors

Info

Publication number: CA3211803A1
Application number: CA3211803A
Authority: CA
Inventors: Jinzhong Zhang; Wei Yong SHEN; Charles Semba; John Zhenze HU; Zhen Qin XIA
Original assignee: Eluminex Biosciences Suzhou Ltd
Current assignee: Eluminex Biosciences Suzhou Ltd
Priority date: 2021-02-27
Filing date: 2022-02-17
Publication date: 2022-09-01
Also published as: TW202246359A; AU2022227047A1; CN116897165A; EP4298127A1; MX2023009956A; JP2024507397A; KR20230150858A; WO2022179432A1

Abstract

An antibody fusion protein comprises an antibody against IL-6 receptor or an antigen-binding fragment thereof linked to a VEGF binding unit comprising a plurality of Ig-like domains of a first VEGF receptor, a second human VEGF receptor, and/or a third human VEGF receptor. The antibody fusion protein is useful in treating or controlling an ocular disease, condition, or disorder that has etiology in aberrant angiogenesis or inflammation.

Description

2 FACTORS
BACKGROUND OF THE INVENTION
[0001] The present invention relates to antibody fusion proteins targeting interleukin-6 receptor ("IL-6R") and angiogenic factors. In particular, the present invention relates to antibody fusion proteins targeting IL-6R and members of the family of vascular endothelial growth factors ("VEGF family members"). More particular, the present invention relates to such fusion proteins, their uses, and processes for production.
[0002] The major cellular components of the mammalian vascular system are the endothelium, smooth muscle cells, and pericytes. Endothelial cells form the lining of the inner surface of all blood vessels in the mammal and constitute a non-thrombogenic interface between blood and tissue. Therefore, the proliferation of endothelial cells is an important component for the development of new capillaries and blood vessels which, in turn, is a necessary process for the growth and/or regeneration of mammalian tissues.

[0003] A family of secreted polypeptides has been shown to play an extremely important role in promoting endothelial cell proliferation and angiogenesis. A
pathological feature of uncontrolled angiogenesis caused by VEGF over-expression is increased vascular permeability, which results in fluid leakage into, and swelling of, the surrounding tissues. In mammals, this family consists of five related growth factors having highly conserved receptor-binding structure: vascular endothelial growth factors A-D ("VEGF-A,"
"VEGF-B,"
"VEGF-C," and "VEGF-D") and placental growth factor ("P1GF"). In this disclosure, this family of growth factors is also referred to as the VEGF family.

[0004] The cytokine interleukin-6 ("IL-6") plays an important role in host defense against environmental stress such as infection and injury. Under physiological conditions, IL-6 is barely detectable, but its levels can increase more than 100,000-fold during early phase of inflammation. However, not all occurrences of IL-6 stimulation are beneficial.
Dysregulated, persistent production of IL-6 has been implicated in the development of various autoimmune, chronic inflammatory diseases. There has been evidence that unchecked production of IL-6 in inflamed tissues induces excess production of VEGF-A and VEGF-C.

[0005] The VEGF-family growth factors act through a family of cognate receptor tyrosine kinases, which exist only on the surface of vascular endothelial cells, to stimulate formation of blood vessels: VEGF receptor-1 ("VEGFR-1," also known as "fit-1"), VEGF
receptor-2 ("VEGFR-2," also known as "KDR" in humans and "flk-1" in mice), VEGF
receptor-3 ("VEGFR-3," also known as "fit-4").

[0006] VEGF-A (also sometimes simply referred to as VEGF) has emerged as the most important member of this family of growth factors. Human VEGF-A is expressed in a variety of tissues as multiple homodimeric forms (121, 145, 165, 183, 189 and 206 amino acids per monomer), wherein each form arises as a result of alternative splicing of a single RNA transcript.

[0007] Since VEGFs promote vascular endothelial cell proliferation and angiogenesis, they may be useful for the therapeutic treatment of numerous conditions in which a growth-promoting activity on the vascular endothelial cells is beneficially important; for example, in treatment of ulcers, vascular injuries, and myocardial infarction.

[0008] In contrast, however, while vascular endothelial proliferation is desirable under certain circumstances, vascular endothelial proliferation and angiogenesis are also undesirable components of a variety of diseases and disorders including tumor growth and metastasis, rheumatoid arthritis, psoriasis, atherosclerosis, diabetic retinopathy, retrolental fibroplasia, neovascular glaucoma, neovascular age-related macular degeneration, hemangiomas, immune rejection of transplanted corneal tissue and other tissues, and chronic inflammation. In individuals suffering from any of these disorders, one would want to inhibit, or at least substantially reduce, the endothelial proliferating activity of VEGFs.

[0009] Each of fit-1, KDR, and flt-4 tyrosine kinase receptors has seven extracellular immunoglobulin-like ("Ig-like") domains that are available for ligand binding, a transmembrane domain that serves to anchor the receptor on the surface of cells in which it is expressed and an intracellular catalytic tyrosine kinase domain. Flt-1 binds VEGF-A, VEGF-B, and P1GF. KDR binds VEGF-A, VEGF-C, and VEGF-D. Flt-4 binds VEGF-C and VEGF-D.

[0010] In view of the role of the growth factors of the VEGF family in vascular endothelial proliferation and angiogenesis, and the role that these processes play in many different diseases and disorders, treatments have been devised that target the control of these growth factors. However, anti-VEGF therapy alone has not been able to block completely the progression of angiogenic diseases.

[0011] Therefore, it is desirable to have a pharmacological means for more completely reducing or inhibiting one or more of the biological activities of these growth factors in patients whose pathological conditions are rooted in aberrant angiogenesis. It is also desirable to have a pharmacological means for improved treatment or control of pathological conditions that are rooted in aberrant angiogenesis.
SUMMARY OF THE INVENTION

[0012] As used herein, the term "control" also includes reduction, alleviation, amelioration, or prevention.

[0013] In general, the present invention provides antibody fusion or chimeric proteins, methods of producing and compositions comprising the same, and methods for treating or controlling at least a pathological condition in a subject, which condition has etiology in aberrant angiogenesis. In this disclosure the terms "fusion protein" and "chimeric protein"
are used interchangeably.

[0014] In one aspect, the present invention provides antibody fusion or chimeric proteins or antigen-binding fragments or antigen-binding domains thereof that are capable of binding substantially to IL-6R, including either the membrane-bound or the soluble form of IL-6R, and one or more VEGF family members; thereby, concurrently reducing or inhibiting both IL-6 and VEGF family member signaling transduction.

[0015] In another aspect, an antibody fusion or chimeric protein of the present invention comprises an antibody against IL-6R or an antigen-binding fragment or domain thereof linked to a VEGF binding unit that comprises an Ig-like domain selected from the group consisting of Ig-like domains of a first VEGF receptor, a second VEGF
receptor, a third VEGF receptor, and combinations thereof. A VEGF binding unit, as used herein, comprises a polypeptide that binds to, or substantially to, a VEGF family member. Thus, in one aspect, an antibody fusion protein of the present invention may be viewed at least as a bispecific construct that can bind to two different ligands. In some embodiments, said VEGF binding unit comprises a plurality of Ig-like domains of one or more VEGF receptors.

[0016] In still another aspect, said IL-6R is human IL-6R.

[0017] In still another aspect, an antibody fusion or chimeric protein of the present invention comprises an antibody against IL-6R or an antigen-binding fragment or domain thereof; wherein at least one of: (1) a light chain or an antigen-binding fragment or domain thereof and (2) a heavy chain or an antigen-binding fragment or domain thereof is linked to a VEGF binding unit that comprises a plurality of Ig-like domains selected from the group consisting of those of a first VEGF receptor, a second VEGF receptor, a third VEGF receptor, and combinations thereof.

[0018] In still another aspect, said VEGF binding unit comprises: (1) (a) Ig-like domain 2, or substantially Ig-like domain 2, of human VEGFR-1 (or fit-1); and (b) Ig-like domain 3, or substantially Ig-like domain 3, of human VEGFR-2 (or KDR); or (2) at least an Ig-like domain selected from the group consisting of Ig-like domains 1, 2, and 3, or substantially Ig-like domains 1, 2, and 3, of human VEGFR-3 (or fit-4).

[0019] In yet another aspect, each of the light chains or an antigen-binding fragment or domain thereof and the heavy chains or an antigen-binding fragment or domain thereof of the antibody against IL-6R or an antigen-binding thereof is linked to a VEGF
binding unit comprising: (a) Ig-like domain 2, or substantially Ig-like domain 2, of human VEGFR-1(or fit-1); and (b) Ig-like domain 3, or substantially Ig-like domain 3, of human VEGFR-2 (or KDR).

[0020] In yet another aspect, each of the light chains or an antigen-binding fragment or domain thereof of the antibody against IL-6R or an antigen-binding thereof is linked to a first VEGF binding unit comprising: (a) Ig-like domain 2, or substantially Ig-like domain 2, of human VEGFR-1(or fit-1); and (b) Ig-like domain 3, or substantially Ig-like domain 3, of human VEGFR-2 (or KDR); and each of the heavy chains or an antigen-binding fragment or domain thereof of the antibody against IL-6R or an antigen-binding thereof is linked to a second VEGF binding unit comprising: (a) Ig-like domains 1 and 2, or substantially Ig-like domains 1 and 2, of human VEGFR-3; or (b) Ig-like domains 2 and 3, or substantially Ig-like domains 2 and 3, of human VEGFR-3; or Ig-like domains 1, 2, and 3, or substantially Ig-like domains 1, 2, and 3, of human VEGFR-3.

[0021] In yet another aspect, each of the heavy chains or an antigen-binding fragment or domain thereof of the antibody against IL-6R is linked to a VEGF binding unit selected from the group consisting of: (1) a first VEGF binding unit comprising (a) Ig-like domain 2, or substantially Ig-like domain 2, of human VEGFR-1(or fit-1); and (b) Ig-like domain 3, or substantially Ig-like domain 3, of human VEGFR-2 (or KDR); (2) a second VEGF
binding unit comprising Ig-like domains 1 and 2, or substantially Ig-like domains 1 and 2, of human VEGFR-3 (or fit-4); and (3) combinations of said first and second VEGF binding units.

[0022] In still another aspect, the present invention provides an isolated nucleic acid molecule encoding at least one of said antibody fusion or chimeric protein.

[0023] In still another aspect, the present invention provides a vector that comprises said nucleic acid molecule, including an expression vector comprising said nucleic molecule operatively linked to an expression control sequence. As used herein, the phrase "operatively linked" refers to components of a construct being placed in a functional relationship with each another and each component retaining its function. A nucleic acid is "operatively linked" when it is placed in a functional relationship with another nucleic acid sequence. For example, DNA for a pre-sequence or secretory leader is "operatively linked" to DNA for a polypeptide if it is expressed as a pre-protein that participates in the secretion of the polypeptide; a promoter or enhancer is operatively linked to a coding sequence if it affects the transcription of the sequence; or a ribosome binding site is operatively linked to a coding sequence if it is positioned so as to facilitate translation.

[0024] In still another aspect, the present invention provides a host-vector system for the production of said antibody fusion or chimeric protein that comprises the expression vector in a suitable host cell.

[0025] In another aspect, the present invention provides a method of producing an antibody fusion or chimeric protein, which method comprises: (a) growing cells of the host-vector system under conditions permitting production of the antibody fusion or chimeric protein; and (b) recovering the antibody fusion or chimeric protein so produced.

[0026] In still another aspect, the present invention provides a method for treating or controlling at least a disease, condition, or disorder, in a subject, which has etiology in a condition selected from the group consisting of aberrant angiogenesis, inflammation, and combinations thereof.

[0027] In yet another aspect, the present invention provides a method for treating or controlling at least a disease, condition, or disorder, in a subject, which has etiology in aberrant angiogenesis and/or inflammation. In certain embodiments, such disease, condition, or disorder is an ocular disease, condition, or disorder. In certain other embodiments, such disease, condition, or disorder involves tumor growth and metastasis. In other embodiments, such disease, condition, or disorder is rheumatoid arthritis, psoriasis, or atherosclerosis.

[0028] Other features and advantages of the present invention will become apparent from the following detailed description and claims.
BRIEF DESCRIPTION OF THE DRAWINGS

[0029] Figure 1 shows a schematic diagram of a first and a second embodiment of an antibody fusion protein of the present invention, comprising an antibody against human IL-6R, each of the light chain and the heavy chain of which is linked through a flexible linker to a VEGF binding unit comprising Ig-like domain 2 of VEGFR-1 and Ig-like domain 3 of VEGFR-2.

[0030] Figure 2 shows a schematic diagram of a third and a fourth embodiment of an antibody fusion protein of the present invention, comprising an antibody against human IL-6R, the light chain of which is linked through a flexible linker to a first VEGF binding unit comprising Ig-like domain 2 of VEGFR-1 and Ig-like domain 3 of VEGFR-2, and the heavy chain of which is linked through a flexible linker to a second VEGF binding unit comprising Ig-like domains 2 and 3 of VEGFR-3.

[0031] Figure 3 shows a schematic diagram of a fifth embodiment of an antibody fusion protein of the present invention, comprising scFvs of an antibody against human IL-6R, each variable domain of the heavy chains of which is linked to a Fc domain which is in turn linked through a flexible linker to a VEGF binding unit comprising Ig-like domain 2 of VEGFR-1 and Ig-like domain 3 of VEGFR-2.

[0032] Figure 4 shows a schematic diagram of a sixth embodiment of an antibody fusion protein of the present invention, comprising scFvs of an antibody against human IL-6R, each variable domain of the heavy chains of which is linked through a flexible linker to a VEGF
binding unit comprising Ig-like domain 2 of VEGFR-1 and Ig-like domain 3 of VEGFR-2, which in turn is linked through a flexible linker to a Fc domain.

[0033] Figure 5 shows a schematic diagram of a seventh embodiment of an antibody fusion protein of the present invention, comprising scFvs of an antibody against human IL-6R, each variable domain of the heavy chains of which is linked through a flexible linker to a first VEGF binding unit comprising Ig-like domain 2 of VEGFR-1 and Ig-like domain 3 of VEGFR-2, which in turn is linked through a flexible linker to a Fc domain, which in turn is linked through a flexible linker to a second VEGF binding unit comprising Ig-like domains 1 and 2 of VEGFR-3.

[0034] Figure 6 shows a schematic diagram of an eighth embodiment of an antibody fusion protein of the present invention, comprising scFvs of an antibody against human IL-6R, each variable domain of the heavy chains of which is linked through a flexible linker to a first VEGF binding unit comprising Ig-like domain 2 of VEGFR-1 and Ig-like domain 3 of VEGFR-2, and a second VEGF binding unit comprising Ig-like domains 1 and 2 of VEGFR-3, which in turn is linked through a flexible linker to a Fc domain.

[0035] Figure 7A-D show molecular designs of six antibody fusion proteins (B781401-781406) of the present invention.

[0036] Figure 8 shows molecular designs of fusion proteins EB-DJ1, EB-vvA, EB-vvB, and EB-vvC of the present invention.

[0037] Figure 9 shows an example of SEC-HPLC chromatograms for the purification of B781401 that was expressed in HEK293 cells.

[0038] Figure 10 shows an example of SEC-HPLC chromatograms for the purification of B781401 that was expressed in CHO cells

[0039] Figure 11 shows a comparison of the binding affinities of B781401-781406 to that of aflibercept for recombinant human VEGF-A165 using enzyme linked immunosorbent assay (ELISA).

[0040] Figure 12 shows a comparison of the ELISA binding affinities of 781406 to that of aflibercept for recombinant human VEGF-B167.

[0041] Figure 13 shows a comparison of the ELISA binding affinities of 781406 to that of aflibercept for recombinant human P1GF.

[0042] Figure 14 shows a comparison of the ELISA binding affinities of 781406 to that of tocilizumab for recombinant humanIL-6R.

[0043] Figure 15 shows a comparison of the effect of B781401-781406 to that of aflibercept on inhibiting VEGF-A165-mediated VEGFR-2 signaling in VEGFR-2-NFAT-RE
luciferase reporter cells.

[0044] Figure 16A-B show a comparison of the effect of B781401-781406 to that of tocilizumab on inhibiting IL-6R signaling.

[0045] Figure 17 shows a comparison of the effect of B781401-781406 to that of siltuximab and tocilizumab on inhibiting IL-6R signaling.

[0046] Figure 18 shows a comparison of the ELISA binding affinities of EB-DJ1, EB-vvA, EB-vvB, and EB-vvC to those of aflibercept, B781403, and B781405, for recombinant human VEGF-A165.

[0047] Figure 19 shows a comparison of the ELISA binding affinities of EB-DJ1, EB-vvA, EB-vvB, and EB-vvC to those of aflibercept, B781402, B781403, and B781405, for recombinant human VEGF-B167.

[0048] Figure 20 shows a comparison of the ELISA binding affinities of EB-DJ1, EB-vvA, EB-vvB, and EB-vvC to those of aflibercept, B781403, and B781405, for recombinant human P1GF.

[0049] Figure 21 shows a comparison of the ELISA binding affinities of EB-DJ1, EB-vvA, EB-vvB, and EB-vvC to those of tocilizumab, B781402, B781403, and B781405, for recombinant humanIL-6R.
DETAILED DESCRIPTION OF THE INVENTION

[0050] In general, the present invention provides an antibody fusion or chimeric protein or an antigen-binding fragment or domain thereof that is capable of binding substantially to IL-6R and one or more VEGF family members; thereby, reducing or inhibiting both IL-6 and VEGF family member signaling transduction. In this disclosure, the term "antibody fusion protein" is sometimes used in place of "antibody fusion or chimeric protein."
In one aspect, an antibody fusion protein or an antigen-binding fragment thereof is capable of binding substantially to IL-6R and one or more VEGF family members; thereby, reducing or inhibiting signaling transduction of IL-6 and VEGF family members.

[0051] In another aspect, an antibody fusion or chimeric protein of the present invention comprises an antibody against IL-6R or an antigen-binding fragment or domain thereof linked to a VEGF binding unit that comprises a plurality of Ig-like domains selected from the group consisting of those of a first VEGF receptor, a second VEGF receptor, and a third VEGF receptor.

[0052] An antibody fusion protein of the present invention has advantages in that it can substantially bind, and thereby inhibit the action of, both membrane-bound IL-6R and soluble IL-6R. It can inhibit all three signaling pathways including classic, trans-signaling and trans-presentation pathways while an antibody fusion protein including an IL-6 antibody can only inhibit the free form of IL-6.

[0053] In still another aspect, said IL-6R is human IL-6R.

[0054] In yet another aspect, said VEGF receptors are human VEGF receptors.

[0055] In still another aspect, an antibody fusion or chimeric protein of the present invention comprises an antibody against IL-6R or an antigen-binding fragment or domain thereof; wherein one of: (1) at least a light chain or an antigen-binding fragment or domain thereof and (2) a heavy chain or an antigen-binding fragment or domain thereof is linked to a VEGF binding unit that comprises an Ig-like domain selected from the group consisting of those of a first VEGF receptor, a second VEGF receptor, and a third VEGF
receptor. In certain embodiments, such VEGF binding unit comprises a plurality of Ig-like domains selected from the group consisting of those of a first VEGF receptor, a second VEGF receptor, and a third VEGF receptor. In one embodiment, an antibody fusion or chimeric protein of the present invention comprises an antibody against IL-6R or an antigen-binding fragment or domain thereof; wherein each of a light chain or an antigen-binding fragment or domain thereof and a heavy chain or an antigen-binding fragment or domain thereof is linked to a VEGF binding unit that comprises a plurality of Ig-like domains selected from the group consisting of those of a first VEGF receptor, a second VEGF receptor, and a third VEGF
receptor.

[0056] In still another aspect, said VEGF binding unit comprises: (1) (a) Ig-like domain 2, or substantially Ig-like domain 2, of human VEGFR-1 (or fit-1); and (b) Ig-like domain 3, or substantially Ig-like domain 3, of human VEGFR-2 (or KDR); or (2) at least an Ig-like domain selected from the group consisting of Ig-like domains 1, 2, 3, and combinations thereof of VEGFR-3 (or flt4), or the group consisting of domains substantially the same as said Ig-like domains of VEGFR-3. In one embodiment, the VEGF binding unit comprises: (a) Ig-like domains 1 and 2, or substantially Ig-like domains 1 and 2; or (b) Ig-like domains 2 and 3, or substantially Ig-like domains 2 and 3; or (c) Ig-like domains 1, 2 and 3, or substantially Ig-like domains 1, 2, and 3 of human VEGFR-3.

[0057] In yet another aspect, each of the light chains or an antigen-binding fragment or domain thereof and the heavy chains or an antigen-binding fragment or domain thereof of the antibody against IL-6R or an antigen-binding thereof is linked to a VEGF
binding unit comprising: (a) Ig-like domain 2, or substantially Ig-like domain 2, of human VEGFR-1(or fit-1); and (b) Ig-like domain 3, or substantially Ig-like domain 3, of human VEGFR-2 (or KDR).

[0058] In still another aspect, the light chains or an antigen-binding fragment or domain thereof of the antibody against IL-6R or an antigen-binding thereof is linked to a first VEGF
binding unit comprising: (a) Ig-like domain 2, or substantially Ig-like domain 2, of human VEGFR-1 (or fit-1); and (b) Ig-like domain 3, or substantially Ig-like domain 3, of human VEGFR-2 (or KDR); and the heavy chains or an antigen-binding fragment or domain thereof of the antibody against IL-6R or an antigen-binding thereof is linked to a second VEGF
binding unit comprising Ig-like domains 1 and 2, or substantially Ig-like domains 1 and 2, of human VEGFR-3 (or fit-4). In one embodiment, the heavy chains or an antigen-binding fragment or domain thereof of the antibody against IL-6R or an antigen-binding thereof is linked to a second VEGF binding unit comprising Ig-like domains 2 and 3, or substantially Ig-like domains 2 and 3, of human VEGFR-3 (or fit-4).

[0059] As disclosed herein, an "antigen-binding fragment or domain" of a light chain or a heavy chain of an antibody refers to a fragment or portion of such antibody that comprises a complementarity determining region ("CDR") of a variable domain of such antibody. In one embodiment, an antigen-binding fragment or domain of such antibody comprises a variable domain of the light chain or the heavy chain of such antibody. An antigen-binding fragment or domain of a heavy chain may further comprise a Fc domain. Other non-limiting examples of antibody fragments or domains include single-domain antibody (sdAb, also known as nanobody), minibody, diabody, tribody, scFv-Fc antibody, (Fab')2, and others known in the art. Non-limiting examples of sdAbs are nanobodies against human IL-6R as disclosed in US
Patent 10,618,964; more specifically, vobarilizumab, of which an amino acid sequence is listed below as SEQ ID NO: 73.

[0060] In one aspect, an antibody fusion protein of the present invention comprises: (1) a heavy chain having an amino acid sequence selected from the group consisting of SEQ ID
NO: 34, 38, 42, 46, 78, 82, 86, 90, 94, and 98; (1) a light chain having an amino acid sequence selected from the group consisting of SEQ ID NO: 36, 40, 44, 48, 80, 84, 88, 92, 96, and 100.

[0061] In embodiment 5, an antibody fusion protein of the present invention comprises a pair or a dimer of IL-6R single chain variable fragments ("IL-6R scFvs"), each of which is linked sequentially to a Fc domain of IgG1 and a VEGF binding unit that comprises: (a) Ig-like domain 2, or substantially Ig-like domain 2, of human VEGFR-1 (or fit-1);
and (b) Ig-like domain 3, or substantially Ig-like domain 3, of human VEGFR-2 (or KDR).
The amino acid sequence of this embodiment is listed in SEQ ID NO: 60. The nucleic acid sequence of this embodiment is listed in SEQ ID NO: 59. In one aspect, said IgG1 is human IgGl.

[0062] In embodiment 6, an antibody fusion protein of the present invention comprises a pair or dimer of IL-6R scFvs; wherein the carboxy terminus (C-terminus) of each IL-6R scFv is linked to a VEGF binding unit that comprises: (a) Ig-like domain 2, or substantially Ig-like domain 2, of human VEGFR-1 (or fit-1); and (b) Ig-like domain 3, or substantially Ig-like domain 3, of human VEGFR-2 (or KDR); and the carboxy terminus of each VEGF
binding unit is linked to a Fc domain of IgGl. The amino acid sequence of this embodiment is listed in SEQ ID NO: 62. The nucleic acid sequence of this embodiment is listed in SEQ ID NO:
61. In one aspect, said IgG1 is human IgGl.

[0063] In embodiment 7, an antibody fusion protein of the present invention comprises a pair or dimer of IL-6R scFvs; wherein the carboxy terminus of each IL-6R scFv is linked to a first VEGF binding unit that comprises: (a) Ig-like domain 2, or substantially Ig-like domain 2, of human VEGFR-1 (or fit-1); and (b) Ig-like domain 3, or substantially Ig-like domain 3, of human VEGFR-2 (or KDR); the carboxy terminus of each first VEGF binding unit is linked to a Fc domain of IgGl; and the carboxy terminus of the Fc domain is linked to a second VEGF binding unit that comprises Ig-like domains 1 and 2, or substantially Ig-like domains 1 and 2, of human VEGFR-3 (or fit-4). The amino acid sequence of this embodiment is listed in SEQ ID NO: 64. The nucleic acid sequence of this embodiment is listed in SEQ ID NO: 63.

[0064] In embodiment 8, an antibody fusion protein of the present invention comprises a pair or dimer of IL-6R scFvs; wherein the carboxy terminus of each IL-6R scFv is linked to a first VEGF binding unit that comprises: (a) Ig-like domain 2, or substantially Ig-like domain 2, of human VEGFR-1 (or fit-1); and (b) Ig-like domain 3, or substantially Ig-like domain 3, of human VEGFR-2 (or KDR); the carboxy terminus of each first VEGF binding unit is linked to a second VEGF binding unit that comprises Ig-like domains 1 and 2, or substantially Ig-like domains 1 and 2, of human VEGFR-3 (or fit-4); and the carboxy terminus of the second VEGF binding unit is linked to a Fc domain of IgG1 .
The amino acid sequence of this embodiment is listed in SEQ ID NO: 66. The nucleic acid sequence of this embodiment is listed in SEQ ID NO: 65.

[0065] Embodiment 9 is similar to embodiment 5, except that the Fc domain is linked to the VEGF binding unit by a linker having a different length. The amino acid sequence of this embodiment is listed in SEQ ID NO: 74. The nucleic acid sequence of this embodiment is listed in SEQ ID NO: 75.

[0066] In embodiment 10, an antibody fusion protein of the present invention comprises a pair or dimer of IL-6R scFvs; wherein the amino terminus (N-terminus) of each IL-6R scFv is linked to the carboxy terminus (C-terminus) of a Fc domain of IgGl, the amino terminus of which is linked to a VEGF binding unit that comprises: (a) Ig-like domain 2, or substantially Ig-like domain 2, of human VEGFR-1 (or fit-1); and (b) Ig-like domain 3, or substantially Ig-like domain 3, of human VEGFR-2 (or KDR). The amino acid sequence of this embodiment is listed in SEQ ID NO: 76. The nucleic acid sequence of this embodiment is listed in SEQ
ID NO: 77.

[0067] In any of the foregoing embodiments, a VEGF binding unit may be linked to a scFv, a Fc domain, or another VEGF binding unit either directly or through a linker. It is preferable that a VEGF binding unit is linked to a scFv, a Fc domain, or another VEGF
binding unit through a linker.

[0068] In still another embodiment, an antibody fusion protein of the present invention comprises a (Fab fragment of the antibody against IL-6R, wherein each of the light chains and heavy chains is linked to a VEGF binding unit.

[0069] In another embodiment, an antibody fusion protein of the present invention comprises a minibody of the antibody against IL-6R, wherein each of the light chains and heavy chains is linked to a VEGF binding unit. Such heavy chains may include the Fc region.

[0070] In one embodiment, said antibody against human IL-6R ("hIL-6R") comprises an antibody known as tocilizumab, which is described, for example, in U.S. Patent 10,323,095;
7,479,543; and 5,795,965.

[0071] In one aspect, a heavy chain of an antibody fusion protein of the present invention comprises heavy-chain complementarity determining regions CDR1, CDR2, and CDR3 ("HCCDR1," "HCCDR2," and "HCCDR3") listed in SEQ ID NO: 53, 54, and 55.

[0072] In another aspect, a light chain of an antibody fusion protein of the present invention comprises light-chain complementarity determining regions CDR1, CDR2, and CDR3 ("LCCDR1," "LCCDR2," and "LCCDR3") listed in SEQ ID NO: 56, 57, and 58.

[0073] Other antibodies against hIL-6R may be used in an antibody fusion protein of the present invention; such as sarilumab, described in U.S. Patent 7,582,298; or satralizumab, described in U.S. Patent 8,562,991. In some embodiments, an antibody fusion protein of the present invention may also be generated by linking the heavy chains and light chains of sarilumab (SEQ ID NO: 49 and 50) or satralizumab (SEQ ID NO: 51 and 52) to VEGF
binding units, as described herein. For example, a heavy chain and a light chain of sarilumab or satralizumab may be linked through flexible linkers to VEGF binding units, each comprising polypeptides of SEQ ID NO: 6 and 8. In other embodiments, a heavy chain of tocilizumab or satralizumab is linked through a flexible linker to a VEGF
binding unit comprising a polypeptide of SEQ ID NO: 10; and a light chain of sarilumab or satralizumab is linked through a flexible linker to a VEGF binding unit comprising polypeptides of SEQ
ID NO: 6 and 8.

[0074] A VEGF binding unit included in an antibody fusion protein of the present invention is capable of binding at least one member of the VEGF family ("VEGF
family member"); thereby, rendering said at least one VEGF family member substantially unavailable for binding to a VEGF receptor on endothelial cells. As a result, said antibody fusion protein substantially inhibits biological activity of said at least one VEGF family member in promoting angiogenesis; thereby, controlling a pathological condition having etiology in aberrant angiogenesis.

[0075] In some embodiments, the present invention also provides a binding construct that comprises or consists of a plurality of antibody fusion or chimeric proteins as herein described that are linked to or associated with each other by covalent bonds or other forms of attachment; wherein the antibody portions of such a binding construct may be the same or different. A binding construct of the present invention is capable of binding IL-6R and at least a VEGF family member or a portion thereof and does so with high affinity.

[0076] The VEGF binding units may be linked to the C-terminus (carboxy terminus) or the N-terminus (amino terminus) of the light chains and heavy chains of the antibody portion.
Preferably, the VEGF binding units are linked to the C-terminus of the light chains and heavy chains of the antibody portion. More preferably, the VEGF binding units are linked to the C-terminus of the light chains and heavy chains of the antibody portion through flexible linkers.

[0077] A light chain or heavy chain of the antibody portion of the antibody fusion protein is preferably linked to one VEGF binding unit. However, a light chain or heavy chain of the antibody portion may be linked to more than one VEGF binding unit. In this case, the VEGF binding units may be joined together directly or through a linker. An antibody fusion protein or a binding construct may further include a heterologous peptide or other chemical moieties. Such additions can modify its properties such as stability, solubility, toxicity, serum half-life, immunogenicity, detectability, or other properties.

[0078] The term "high affinity" is used in a physiological context pertaining to the relative affinity of the antibody fusion protein for IL-6R and VEGF family members in vivo in a mammal, such as a laboratory test animal, a domesticated farm or pet animal, or a human.
Antibody fusion proteins binding IL-6R and various VEGF members in the present invention have characteristic affinities for their ligands in vivo, typically measured in terms of sub-nanomolar dissociation constants (Ka). For the purposes of this invention, an antibody fusion protein of the present invention can bind to IL-6R or its targeted VEGF family member(s) with a Kd less than or equal to about 1, or about 5, or about 10, or about 50, or about 100, or about 500, or about 1000 times the Kd of the natural IL-6/IL-6R or growth factor/receptor pair.

[0079] In one aspect, the Ig-like domains of a VEGF binding unit may be linked together in any order, directly or through an intervening linker.

[0080] In another aspect, a targeted VEGF family member may bind to one or more VEGF binding units of the antibody fusion or chimeric protein.

[0081] In still another aspect, a VEGF binding unit comprises substantially an Ig-like domain of a VEGF receptor.

[0082] In another aspect, a VEGF binding unit comprises two Ig-like domains selected from the group consisting of Ig-like domains of human VEGFR-1, VEGFR-2, and VEGFR-3.

[0083] In still another aspect, each of the light chains and heavy chains of an antibody fusion or chimeric protein of the present invention is linked to a VEGF
binding unit that comprises: (a) Ig-like domain 2, or substantially Ig-like domain 2, of human VEGFR-1 (or fit-1); and (b) Ig-like domain 3, or substantially Ig-like domain 3, of human VEGFR-2 (or KDR). In one embodiment, such VEGF binding units are linked to the C-termini of the light chains and the heavy chains of the antibody portion.

[0084] In still another aspect, each of the light chains of an antibody fusion or chimeric protein of the present invention is linked to a first VEGF binding unit that comprises: (a) Ig-like domain 2, or substantially Ig-like domain 2, of human VEGFR-1 (or fit-1);
and (b) Ig-like domain 3, or substantially Ig-like domain 3, of human VEGFR-2 (or KDR);
and each of the heavy chains of the antibody fusion protein is linked to a second VEGF
binding unit that comprises Ig-like domains 1 and 2, or substantially Ig-like domains 1 and 2, of VEGFR-3 (or fit-4). In another embodiment, the second VEGF binding unit comprises Ig-like domains 2 and 3, or substantially Ig-like domains 2 and 3, of VEGFR-3. In still another embodiment, the second VEGF binding unit comprises at least an Ig-like domain selected from the group consisting of Ig-like domains 1, 2, and 3, or substantially Ig-like domains 1, 2, and 3, of VEGFR-3. In yet another embodiment, such VEGF binding units are linked to the C-termini of the light chains and the heavy chains of the antibody portion.

[0085] In some embodiments, two or more VEGF binding units act together to bind a single ligand molecule of the VEGF family (wherein the ligand may comprise a monomer or dimer). In some other embodiments, the binding units act independently, i.e., each binding unit binds a separate ligand molecule.

[0086] In one embodiment, a polypeptide linker is inserted between the C-terminus of the light chain or heavy chain of the antibody portion and a VEGF binding unit. The polypeptide linker may be the same or different for the light chain and heavy chain.

[0087] In one aspect, the amino acid sequences of the various portions or embodiments of an antibody fusion protein of the present invention are listed in Table 1.
Table 1 Amino Acid Sequences Portion of the Antibody Fusion Protein SEQ ID NO:
Heavy chain of antibody portion 2 Light chain of antibody portion 4 Ig-like domain 2 of human VEGFR-1 6 ("VEGFR-1-D2") Ig-like domain 3 of human VEGFR-2 8 ("VEGFR-2-D3") Ig-like domains 1 and 2 of human VEGFR- 10 3 ("VEGFR-3-D1D2") Flexible linker 1 12 Flexible linker 2 14 Flexible linker 3 68 Flexible linker 4 70 Flexible linker 5 72 Signal peptide 16 Complete heavy chain of embodiment 1 18 Complete light chain of embodiment 1 20 Complete heavy chain of embodiment 2 22 Complete light chain of embodiment 2 24 Complete heavy chain of embodiment 3 26 Complete light chain of embodiment 3 28 Complete heavy chain of embodiment 4 30 Complete light chain of embodiment 4 32 Functional heavy chain of embodiment 1 34 Functional light chain of embodiment 1 36 Functional heavy chain of embodiment 2 38 Functional light chain of embodiment 2 40 Functional heavy chain of embodiment 3 42 Functional light chain of embodiment 3 44 Functional heavy chain of embodiment 4 46 Functional light chain of embodiment 4 48 Tocilizumab heavy chain 49 Tocilizumab light chain 50 Satralizumab heavy chain 51 Satralizumab light chain 52 Sarilumab HCCDR1 53 Sarilumab HCCDR2 54 Sarilumab HCCDR3 55 Sarilumab LCCDR1 56 Sarilumab LCCDR2 57 Sarilumab LCCDR3 58 Embodiment 5 comprising scFv (EB-DJ1) 60 Embodiment 6 comprising scFv (EB-vvB) 62 Embodiment 7 comprising scFv 64 Embodiment 8 comprising scFv 66 Vobarilizumab 73 Embodiment 9 comprising scFv (EB-vvA) 74 Embodiment 10 comprising scFv (EB-vvC) 76 Heavy chain of B781401 78 Light chain of B781401 80 Heavy chain of B781402 82 Light chain of B781402 84 Heavy chain of B781403 86 Light chain of B781403 88 Heavy chain of B781404 90 Light chain of B781404 92 Heavy chain of B781405 94 Light chain of B781405 96 Heavy chain of B781406 98 Light chain of B781406 100 Ig-like domains 1, 2, and 3 of human 102 VEGFR-3 ("VEGFR-3-D1D2D3")

[0088] In another aspect, the nucleic acid sequences encoding the amino acid sequences of the various portions or embodiments of an antibody fusion protein of the present invention are listed in Table 2.
Table 2 Nucleic Acid Sequences Portion of the Antibody Fusion Protein SEQ ID NO:
Heavy chain of antibody portion 1 Light chain of antibody portion 3 Ig-like domain 2 of human VEGFR-1 5 ("VEGFR-1-D2") Ig-like domain 3 of human VEGFR-2 7 ("VEGFR-2-D3") Ig-like domains 1 and 2 of human VEGFR- 9 3 ("VEGFR-3-D1D2") Flexible linker 1 11 Flexible linker 2 13 Flexible linker 3 67 Flexible linker 4 69 Flexible linker 5 71 Signal peptide 15 Complete heavy chain of embodiment 1 17 Complete light chain of embodiment 1 19 Complete heavy chain of embodiment 2 21 Complete light chain of embodiment 2 23 Complete heavy chain of embodiment 3 25 Complete light chain of embodiment 3 27 Complete heavy chain of embodiment 4 29 Complete light chain of embodiment 4 31 Functional heavy chain of embodiment 1 33 Functional light chain of embodiment 1 35 Functional heavy chain of embodiment 2 37 Functional light chain of embodiment 2 39 Functional heavy chain of embodiment 3 41 Functional light chain of embodiment 3 43 Functional heavy chain of embodiment 4 45 Functional light chain of embodiment 4 47 Embodiment 5 comprising scFv (EB-DJ1) 59 Embodiment 6 comprising scFv (EB-vvB) 61 Embodiment 7 comprising scFv 63 Embodiment 8 comprising scFv 65 Embodiment 9 comprising scFv (EB-vvA) 75 Embodiment 10 comprising scFv (EB-vvC) 77 Heavy chain of B781401 79 Light chain of B781401 81 Heavy chain of B781402 83 Light chain of B781402 85 Heavy chain of B781403 87 Light chain of B781403 89 Heavy chain of B781404 91 Light chain of B781404 93 Heavy chain of B781405 95 Light chain of B781405 97 Heavy chain of B781406 99 Light chain of B781406 101 Ig-like domains 1, 2, and 3 of human 103 VEGFR-3 ("VEGFR-3-D1D2D3")

[0089] In yet another aspect, the antibody fusion or chimeric protein of the present invention comprises an amino acid sequence that is at least 90% identical to SEQ ID NO: 18, SEQ ID NO: 20, SEQ ID NO: 22, SEQ ID NO: 24, SEQ ID NO: 26, SEQ ID NO: 28, SEQ

ID NO: 30, SEQ ID NO: 32, SEQ ID NO: 60, SEQ ID NO: 62, SEQ ID NO: 64, SEQ ID
NO:
66, SEQ ID NO: 74, or SEQ ID NO: 76.

[0090] In still another aspect, the antibody fusion or chimeric protein of the present invention comprises an amino acid sequence that is at least 95% identical to SEQ ID NO: 18, SEQ ID NO: 20, SEQ ID NO: 22, SEQ ID NO: 24, SEQ ID NO: 26, SEQ ID NO: 28, SEQ

ID NO: 30, or SEQ ID NO: 32, SEQ ID NO: 60, SEQ ID NO: 62, SEQ ID NO: 64, SEQ
ID
NO: 66, SEQ ID NO: 74, or SEQ ID NO: 76.

[0091] In still another aspect, one or more amino acid substitutions can be made in anyone of the above-described amino acid sequences. Preferably, such substitution is a conserved substitution, wherein an amino acid in one of the following groups is substituted with another in the same group: (1) A, S, T; (2) D, E; (3) N, Q; (4) R, K; (5) I, L, M, V; and (6) F, Y, W; and such substitution is selected so as to preserve substantially the binding activity of the fusion polypeptide. In one embodiment, an antibody fusion protein of the present invention having a conserved substitution has a Kd value for IL-6R or VEGF ligand less than about 120% of that before such substitution. Preferably, the Kd value is less than about 110% of that before such substitution. More preferably, the Kd value is less than about 105% of that before such substitution.

[0092] Most conserved substitutions are not expected to produce radical changes in the characteristics of the Ig-like domain or domains of the fusion polypeptide.
However, when it is difficult to predict the exact effect of the substitution in advance of doing so, one skilled in the art will appreciate that the effect will be evaluated by routine screening assays. For example, an Ig-like domain variant typically is made by site-specific mutagenesis of the nucleic acid encoding the intact fusion polypeptide, expression of the variant nucleic acid in recombinant cell culture, purification of the variant fusion polypeptide from the cell culture and detecting the ability of the variant fusion polypeptide to specifically bind to IL-6R or a VEGF ligand. An exemplary binding assay which can be employed to determine if a particular substitution or substitutions in an Ig-like domain or domains affect the capability of the fusion polypeptide to bind to and inhibit the activity of IL-6R or a VEGF
family member is described in the article by Park et al., J. Biol. Chem., 269:25646-25654 (1994).

[0093] The VEGFR-1-D2 binding unit of the fusion protein is capable of binding free VEGF-A, VEGF-B, and placental growth factor ("P1GF") with high affinity (Davis-Smyth et al., EMBO J., 15(18):4919 (1996)). The VEGFR-2-D3 binding unit of the fusion protein is capable of binding free VEGF-A, VEGF-C, and VEGF-D with high affinity (Stuttfeld et al., Life, 61(9):915 (2009)). The VEGFR-3-D1D2 binding unit of the fusion protein is capable of binding free VEGF-C and VEGF-D with high affinity. Thus, a fusion protein of the present invention is capable of substantially inhibiting the angiogenic activity of these VEGF family members on endothelial cells at the site of the disease.

[0094] In still another aspect, the present invention provides isolated nucleic acid molecules encoding heavy chains and light chains of said antibody fusion protein.

[0095] In yet another aspect, the present invention provides isolated nucleic acid molecules encoding said antibody fusion protein; wherein said isolated nucleic acid molecules comprise: (a) a nucleic acid sequence encoding a heavy chain of an antibody against human IL-6R ("hIL-6R antibody") or an antigen-binding fragment or domain thereof;
(b) a nucleic acid sequence encoding a light chain of said hIL-6R antibody or an antigen-binding fragment or domain thereof; and (c) a nucleic acid sequence encoding an Ig-like domain of a VEGF receptor operatively linked to each of said nucleic acid sequence encoding said heavy chain of hIL-6R antibody or an antigen-binding fragment or domain thereof and said nucleic acid sequence encoding said light chain of hIL-6R antibody or an antigen-binding fragment or domain thereof

[0096] In still another aspect, the present invention provides isolated nucleic acid molecules encoding said antibody fusion protein; wherein said isolated nucleic acid molecules comprise: (a) a nucleic acid sequence encoding a heavy chain of an hIL-6R
antibody or an antigen-binding fragment or domain thereof; (b) a nucleic acid sequence encoding a light chain of said hIL-6R antibody or an antigen-binding fragment or domain thereof; and (c) a nucleic acid sequence encoding VEGFR-1-D2 and VEGFR-2-D3 operatively linked to each of said nucleic acid sequence encoding said heavy chain of hIL-6R
antibody or an antigen-binding fragment or domain thereof and said nucleic acid sequence encoding said light chain of hIL-6R antibody or an antigen-binding fragment or domain thereof.

[0097] In still another aspect, the present invention provides isolated nucleic acid molecules encoding said antibody fusion protein; wherein said isolated nucleic acid molecules comprise: (a) a nucleic acid sequence encoding a heavy chain of an hIL-6R
antibody or an antigen-binding fragment or domain thereof, having a sequence listed in SEQ
ID NO: 1; (b) a nucleic acid sequence encoding a light chain of said hIL-6R
antibody or an antigen-binding fragment or domain thereof, having a sequence listed in SEQ ID
NO: 3; and (c) a nucleic acid sequence encoding VEGFR-1-D2 and VEGFR-2-D3, having sequences listed in SEQ ID NO: 5 and 7, which is operatively linked to each of said nucleic acid sequence encoding said heavy chain of hIL-6R antibody or an antigen-binding fragment or domain thereof and said nucleic acid sequence encoding said light chain of hIL-6R antibody or an antigen-binding fragment or domain thereof.

[0098] In still another aspect, the present invention provides isolated nucleic acid molecules encoding said antibody fusion protein; wherein said isolated nucleic acid molecules comprise: (a) a nucleic acid sequence encoding a heavy chain of an hIL-6R
antibody or an antigen-binding fragment or domain thereof; (b) a nucleic acid sequence encoding a light chain of said hIL-6R antibody or an antigen-binding fragment or domain thereof; (c) a nucleic acid sequence encoding VEGFR-3-D1D2 operatively linked to said nucleic acid sequence encoding said heavy chain of hIL-6R antibody or an antigen-binding fragment or domain thereof; and (d) a nucleic acid sequence encoding VEGFR-1-D2 and VEGFR-2-D3 operatively linked to said nucleic acid sequence encoding said light chain of hIL-6R antibody or an antigen-binding fragment or domain thereof. In some embodiments, the nucleic acid sequence encoding VEGFR-3-D1D2 is replaced by a nucleic acid sequence that encodes at least a VEGFR-3 Ig-like domain selected from the group consisting of VEGFR-3-D1, VEGFR-3-D2, and VEGFR3-D3.

[0099] In still another aspect, the present invention provides isolated nucleic acid molecules encoding said antibody fusion protein; wherein said isolated nucleic acid molecules comprise: (a) a nucleic acid sequence encoding a heavy chain of an hIL-6R
antibody or an antigen-binding fragment or domain thereof, having a sequence listed in SEQ
ID NO: 1; (b) a nucleic acid sequence encoding a light chain of said hIL-6R
antibody or an antigen-binding fragment or domain thereof, having a sequence listed in SEQ ID
NO: 3; (c) a nucleic acid sequence encoding VEGFR-3-D1D2, having a sequence listed in SEQ
ID NO: 9, which is operatively linked to said nucleic acid sequence encoding said heavy chain of hIL-6R antibody or an antigen-binding fragment or domain thereof; and (d) a nucleic acid sequence encoding VEGFR-1-D2 and VEGFR-2-D3, having sequences listed in SEQ ID
NO:
and 7, which is operatively linked to said nucleic acid sequence encoding said light chain of hIL-6R antibody or an antigen-binding fragment or domain thereof. In some embodiments, the nucleic acid sequence encoding VEGFR-3-D1D2 is replaced by a nucleic acid sequence that encodes at least a VEGFR-3 Ig-like domain selected from the group consisting of VEGFR-3-D1, VEGFR-3-D2, and VEGFR3-D3.

[00100] In still another aspect, the present invention provides an isolated nucleic acid molecule encoding a heavy chain of said antibody fusion protein that has a sequence listed in SEQ ID NO: 17, 21, 25, 29, 79, 83, 87, 91, 95, or 99; and an isolated nucleic acid molecule encoding a light chain of said fusion protein that has a sequence listed in SEQ ID NO: 19, 23, 27, 31, 81, 85, 89, 93, 97, or 101.

[00101] In yet another aspect, said isolated nucleic acid molecules further can comprise a leading nucleic acid sequence encoding a signal polypeptide. In certain embodiments wherein a VEGF binding unit is linked to the C-terminus of a heavy chain or light chain of the antibody portion, said leading nucleic acid sequence precedes SEQ ID NO: 1 and 3.

[00102] In another aspect, the present invention provides isolated nucleic acid molecules encoding said antibody fusion or chimeric protein; wherein said isolated nucleic acid molecules comprise a nucleic acid sequence that, as a result of the degeneracy of the genetic code, differ in one or more codons from a nucleic acid sequence listed in this disclosure.
Such different nucleic acid sequence is within the scope of the present invention.

[00103] In still another aspect, the present invention provides a vector that comprises any of said nucleic acid molecules, including an expression vector comprising any of said nucleic molecules operatively linked to an expression control sequence. Embodiments of the vector comprise a nucleic acid sequence selected from the group consisting of SEQ ID
NO: 17, SEQ
ID NO: 19, SEQ ID NO: 21, SEQ ID NO: 23, SEQ ID NO: 25, SEQ ID NO: 27, SEQ ID
NO:
29, SEQ ID NO: 31, SEQ ID NO: 59, SEQ ID NO: 61, SEQ ID NO: 63, SEQ ID NO: 65, SEQ ID NO: 75, SEQ ID NO: 77, SEQ ID NO: 79, SEQ ID NO: 81, SEQ ID NO: 83, SEQ

ID NO: 85, SEQ ID NO: 87, SEQ ID NO: 89, SEQ ID NO: 91, SEQ ID NO: 93, SEQ ID
NO:
95, SEQ ID NO: 97, SEQ ID NO: 99, and SEQ ID NO: 101.

[00104] In still another aspect, the present invention provides a host-vector system for the production of said antibody fusion or chimeric protein that comprises the expression vector in a suitable host cell.

[00105] In one aspect, the present invention provides for the construction of a nucleic acid molecules encoding heavy chains and light chains of an antibody fusion protein disclosed herein, which nucleic acid molecules are inserted into vectors that are able to express the antibody fusion protein when introduced into an appropriate host cell.
Appropriate host cells include, but are not limited to, bacterial cells, yeast cells, insect cells, and mammalian cells.
Any of the methods known to one skilled in the art for the insertion of DNA
fragments into a vector may be used to construct expression vectors encoding chimeric polypeptide molecules under control of transcriptional/translational control signals. These methods may include in vitro recombinant DNA and synthetic techniques and in vivo recombinations (genetic recombination) (See Sambrook, et al., Molecular Cloning, A Laboratory Manual, Cold Spring Harbor Laboratory; Current Protocols in Molecular Biology, Eds. Ausubel, et al., Greene Publ. Assoc., Wiley-Interscience, NY).

[00106] Expression of nucleic acid molecules encoding an antibody fusion protein of the present invention may be regulated by a second nucleic acid sequence (a promoter) so that the antibody fusion protein is expressed in a host transformed with the nucleic acid molecules.
For example, expression of the antibody fusion protein described herein may be controlled by any promoter/enhancer element known in the art.

[00107] In general, plasmid vectors containing replicon and control sequences that are derived from species compatible with the host cell are used in connection with these hosts.
The vector ordinarily carries a replication site, as well as marking sequences that are capable of providing phenotypic selection in transformed cells. For example, E. coli is typically transformed using pBR322, a plasmid derived from an E. coli species (see;
e.g., Bolivar et al., Gene, 2:95 (1977)). The plasmid pBR322 contains genes for ampicillin and tetracycline resistance and thus provides easy means for identifying transformed cells. The pBR322 plasmid, or other microbial plasmid or phage, must also contain, or be modified to contain, promoters that can be used by the microbial organism for expression of proteins.

[00108] Those promoters most commonly used in recombinant DNA construction include the 13-lactamase (penicillinase) and lactose promoter systems or a tryptophan (trp) promoter system (Goeddel et al., Nucleic Acids Res., 8:4057 (1980)). While these are the most commonly used, other microbial promoters have been discovered and utilized.
For example, the tac promoter is a synthetically produced DNA promoter produced from the combination of promoters from the trp and lac operons (de Boer et al., PNAS, (1983-01-80 (1):21-25 (1983)). It is commonly used for protein production in Escherichia coil.
(Amann et al., Gene, 25:167 (1983)). Any of these promoters may be used in connection with a method of producing an antibody fusion protein of the present invention.

[00109] In addition to prokaryotes, eukaryotic microbes, such as yeast cultures, may also be used. Saccharomyces cerevisiae, or common baker's yeast, is the most commonly used among eukaryotic microorganisms, although a number of other strains are commonly available. For expression in Saccharomyces, the plasmid YRp7, for example (Stinchcomb et al., Nature, 282:39 (1979)) is commonly used. Other exemplary plasmids are disclosed in US
Patent 4,615,974; Struhl et al., PNAS,76(3):1035 (1979). The plasmid YRp7 contains the trpl gene that provides a selection marker for a mutant strain of yeast lacking the ability to grow without tryptophan, for example, ATCC No. 44,076 or RH218 (Jones, Genetics, 85:23 (1977)). The presence of the trpl lesion as a characteristic of the yeast host cell genome then provides an effective environment for detecting transformation by growth in the absence of tryptophan.

[00110] Suitable promoting sequences in yeast vectors include the promoters for 3-phosphoglycerate kinase (Hitzeman et al., J. Biol. Chem., 255:2073 (1980)) or other glycolytic enzymes, such as glyceraldehyde-3-phosphate dehydrogenase, hexokinase, pyruvate decarboxylas, and glucokinase (Romanos et al., Yeast, 8:423 (1992);
Weinhandl et al., Microb. Cell factories, 13:5 (2014)). In constructing suitable expression plasmids, the termination sequences associated with these genes are also ligated into the expression vector 3' of the sequence desired to be expressed to provide polyadenylation of the mRNA and termination. Other promoters, which have the additional advantage of transcription controlled by growth conditions, such as the promoter region for alcohol dehydrogenase 2, and enzymes responsible for maltose and galactose utilization (Romanos et al., Weinhandl et al., supra).
Any plasmid vector containing yeast-compatible promoter, origin of replication and termination sequences is suitable.

[00111] In addition to microorganisms, cultures of cells derived from multicellular organisms may also be used as hosts. In principle, any such cell culture is workable, whether from vertebrate or invertebrate culture. However, much interest has been in vertebrate cells, and propagation of vertebrate cells in culture (tissue culture) has become a routine procedure in recent years (Tissue Culture, Academic Press, Kruse and Patterson, editors (1973)).
Examples of such useful host cell lines are VERO and HeLa cells, Chinese hamster ovary (CHO) cell lines, and W138, BHK, COS-7, 293, and MDCK cell lines. Expression vectors for such cells ordinarily include (if necessary) an origin of replication, a promoter located in front of the gene to be expressed, along with any necessary ribosome binding sites, RNA
splice sites, polyadenylation sites, and transcriptional terminator sequences.

[00112] For use in mammalian cells, the control functions on the expression vectors are often provided by viral material. For example, commonly used promoters are derived from polyoma, Adenovirus 2, and most frequently Simian Virus 40 (5V40). The early and late promoters of 5V40 virus are particularly useful because both are obtained easily from the virus as a fragment that also contains the 5V40 viral origin of replication (Fiers et al., Nature, 273:113 (1978)). Smaller or larger 5V40 fragments may also be used, provided there is included the approximately 250-bp sequence extending from the HindIII site toward the BglI
site located in the viral origin of replication. Further, it is also possible, and often desirable, to utilize promoter or control sequences normally associated with the desired gene sequence, provided such control sequences are compatible with the host cell systems.

[00113] Thus, according to the invention, expression vectors capable of being replicated in a bacterial, a yeast cell, an insect cell, or a mammalian cell host, comprising an antibody fusion protein-encoding nucleic acid as described herein, are used to transfect the host and thereby direct expression of such nucleic acids to produce the fusion polypeptide, which may then be recovered in a biologically active form. As used herein, a biologically active form includes a form capable of binding to at least a VEGF family member.

[00114] In some embodiments, the host cell can be E. coil, a COS cell, a HEK
293 cell (also known simply as 293 cells), or a Chinese hamster ovary ("CHO") cell.
Preferably, the host cell is a HEK 293 or CHO cell.
Vector Construction

[00115] Construction of suitable vectors containing the desired coding and control sequences employ standard ligation techniques. Isolated plasmids or DNA
fragments are cleaved, tailored, and ligated in the form desired to form the plasmids required. The methods employed are not dependent on the DNA source or intended host. Cleavage is performed by treating with restriction enzyme (or enzymes) in suitable buffer.

[00116] A nucleic acid sequence substantially encoding one or more Ig-like domains of VEGFR-1, VEGFR-2, or VEGR-3 can be produced according to the method disclosed in U.S.
Patent 6,897,294.

[00117] In one embodiment, nucleic acid sequences substantially encoding the Ig-like domain 2 of VEGFR-1 and Ig-like domain 3 of VEGFR-2 are ligated in tandem in the desired order. This construct is then ligated to the 3' end of the nucleic acid sequences encoding the heavy chain and light chain of the hIL-6R antibody. In another embodiment, this construct is ligated to the 3' end of the nucleic acid sequence encoding the light chain of the hIL-6R
antibody. Another nucleic acid construct comprising nucleic acid sequences substantially encoding the Ig-like domains 1 and 2, or 2 and 3, or 1, 2, and 3, of VEGFR-3 is ligated to the 3' end of the nucleic acid sequence encoding the heavy chain of the hIL-6R
antibody. Such an entire nucleic acid sequence is referred to as a chimeric nucleic acid sequence.

[00118] The entire chimeric nucleic acid sequence is then positioned in a vector which contains a promoter in the reading frame with the gene and compatible with the proposed host cell. A number of plasmids, such as those described in U.S. Patents 4,456,748;
5,460,811; 5,888,808; and 6,333,147, having may be used in a production of an antibody fusion protein of the present invention.

[00119] In one embodiment, a chimeric heavy chain and a chimeric light chain of the antibody fusion protein of the present invention is produced according to the method described in U.S. Patent 7,070,959. The chimeric nucleic acid sequence of SEQ
ID NO: 17, 19, 21, 23, 25, 27, 29, 59, 61, 63, 65,75, 77, 79, 81, 83, 85, 87, 89, 91, 93, 95, 97, 99, or 101 is inserted into the expression vector pEE14.1 (Lonza Biologics) having the CMV promoter.

[00120] In one embodiment, CHO K1 cells are transfected with pEE14.1/SEQ ID
NO: 17 and pEE14.1/SEQ ID NO: 19 construct and then grown. The antibody fusion protein obtained from the CHO cells may be purified and characterized by binding assay, as described in U.S.
Patent 7,070,959.

[00121] Similarly, CHO K1 or HEK293 cells are transfected with a pair of vectors pEE14.1/SEQ ID NO: 21 and pEE14.1/SEQ ID NO: 23; or pEE14.1/SEQ ID NO: 25 and pEE14.1/SEQ ID NO: 27; or pEE14.1/SEQ ID NO: 29 and pEE14.1/SEQ ID NO: 31, or pcDNA3.4/SEQ ID NO: 79 and pcDNA3.4/SEQ ID NO: 81, or pcDNA3.4/SEQ ID NO: 83 and pcDNA3.4/SEQ ID NO: 85, or pcDNA3.4/SEQ ID NO: 87 and pcDNA3.4/SEQ ID NO:
89, or pcDNA3.4/SEQ ID NO: 91 and pcDNA3.4/SEQ ID NO: 93, or pcDNA3.4/SEQ ID
NO: 95 and pcDNA3.4/SEQ ID NO: 97, or pcDNA3.4/SEQ ID NO: 99 and pcDNA3.4/SEQ
ID NO: 101, construct and grown. Antibody fusion proteins obtained from these CHO or HEK293 cells may be similarly purified and characterized.

[00122] In one embodiment, an antibody fusion protein of the present invention can bind to hIL-6R and VEGF family members with Kd 10-9M. In another embodiment, an antibody fusion protein of the present invention can bind to VEGF family members with Kd 5x10-1 M. In still another embodiment, an antibody fusion protein of the present invention can bind to VEGF family members with Kd 10' M.

[00123] In one aspect, the present invention provides compounds, compositions, and methods for treating or controlling a disease, condition, or disorder having etiology in aberrant angiogenesis.

[00124] In another aspect, the present invention provides a method for treating or controlling at least an ocular disease, condition, or disorder, in a subject, which has etiology in aberrant angiogenesis. The method comprises administering to a subject in need of such treating or controlling a composition comprising an antibody fusion protein herein disclosed.
Such an antibody fusion protein comprises a pair of heavy chain and light chain having SEQ

ID NO: 18 and 20; or SEQ ID NO: 22 and 24; or SEQ ID NO: 26 and 28; or SEQ ID
NO: 30 and 32, or SEQ ID NO: 78 and 80; or SEQ ID NO: 82 and 84; or SEQ ID NO: 86 and 88; or SEQ ID NO: 90 and 100. In one embodiment, an antibody fusion protein used in such a method can comprise a pair or dimer of proteins having a sequence as listed in SEQ ID NO:
60, 62, 64, 66, 74, or 76. In another embodiment, an antibody fusion protein used in such a method can comprise a pair or dimer of proteins having a sequence that begins at amino acid 17 of SEQ ID NO: 60, 62, 64, 66, 74, or 76.

[00125] In still another aspect, said ocular disease, condition, or disorder is selected from the group consisting of: choroidal neovascularization, neovascular age-related macular degeneration (wet age-related macular degeneration), polypoidal choroidal vasculopathy ("PCV"), myopic choroidal neovascularization, vascular leak, macular edema resulting from diabetes, uveitis, central and branch retinal vein occlusion, non-proliferative and proliferative diabetic retinopathy, retinopathy of prematurity, corneal neovascularization, corneal inflammation, and neovascular glaucoma.

[00126] In one embodiment, the subject is administered with a dose of about 25-micrograms of the fusion polypeptide. In another embodiment, the subject is administered with a dose of about 50-4000, about 100-4000, about 500-4000, about 1000-4000, about 2000-4000, about 50-3000, about 50-2000, about 50-1000, or about 50-500 micrograms of the fusion polypeptide.

[00127] In still another aspect, the composition comprising the fusion polypeptide is in the form of an eye drop or an ocular injection (such as intravitreal, intracameral, pen-orbital, subtenon, subretinal, or suprachoroidal injection). Such a composition comprises an ophthalmic composition. An antibody fusion protein of the present invention may also be incorporated in a medical device that is implantable into or near a diseased tissue.

[00128] In one embodiment, the present invention provides a method or composition for treating or controlling an anterior-segment disease, condition, or disorder;
such as corneal neovascularization, corneal inflammation, or neovascular glaucoma. The composition comprising the fusion polypeptide may be in the form of an eye drop or intracameral or subconjunctival injection. In another embodiment, the present invention provides a method or composition for treating or controlling a posterior-segment disease, condition, or disorder;

such as choroidal neovascularization, neovascular age-related macular degeneration (wet age-related macular degeneration), polypoidal choroidal vasculopathy ("PCV"), myopic choroidal neovascularization, vascular leak, macular edema resulting from diabetes, uveitis, central and branch retinal vein occlusion, non-proliferative and proliferative diabetic retinopathy, retinopathy of prematurity. In this case, the composition comprising the fusion polypeptide may be administered in the form of an intravitreal injection.

[00129] In yet another aspect, an eye drop is administered to the subject at least once per day, at least once per week, or at least once per month until the disease, condition, or disorder is substantially treated or controlled.

[00130] In yet another aspect, the composition is administered via sustained drug release to the subject for a period of at least one month, at least two months, at least three months, or at least six months.

[00131] In still another aspect, an intravitreal injection or an injection into, or near, a diseased tissue is administered to the subject according to a regimen recommended by a medical practitioner for a particular patient. For example, an injection may be administered at least once per month, at least once every two months, at least once every three months, or at least once every six months until the disease, condition, or disorder is substantially treated or controlled. In one embodiment, treatment may be administered more frequently at the beginning, and then less frequently after a period of time. Such period of time may be determined by a medical practitioner.

[00132] The concentration of an antibody fusion protein of the present invention in such an ophthalmic composition can be in the range from about 0.1 to about 200 mg/ml (or, alternatively, from about 0.25 to about 200 mg/ml, or from about 0.25 to about 160 mg/ml, or from about 0.5 to about 100 mg/ml, or from about 0.25 to about 50 mg/ml, or from about 0.5 to about 200 mg/ml, or from about 0.5 to about 160 mg/ml, or from about 0.5 to about 100 mg/ml, or from about 0.5 to about 50 mg/ml, or from about 1 to about 200 mg/ml, or from 1 to about 160 mg/ml, or from about 0.5 to about 100 mg/ml, or from about 1 to about 50 mg/ml).

[00133] In still another aspect, a method for preparing a composition of the present invention comprises combining: (a) an amount of an antibody fusion protein of the present invention; and (b) a physiologically acceptable carrier.

[00134] In one embodiment, such a physiologically acceptable carrier can be a sterile saline solution or a physiologically acceptable buffer. In another embodiment, such a carrier comprises a hydrophobic medium, such as a pharmaceutically acceptable oil. In still another embodiment, such as carrier comprises an emulsion of a hydrophobic material and water. In yet another embodiment, an antibody fusion protein of the present invention may be associated or linked with a high-molecular weight material to provide a long circulation time.

[00135] Physiologically acceptable buffers include, but are not limited to, a phosphate buffer or a Tris-HC1 buffer (comprising tris(hydroxymethyl)aminomethane and HC1). For example, a Tris-HC1 buffer having pH of 7.4 comprises 3 g/1 of tris(hydroxymethyl)aminomethane and 0.76 g/1 of HC1. In yet another aspect, the buffer is 10X phosphate buffer saline ("PBS") or 5X PBS solution. Non-limiting examples of buffers used for injectable compositions comprising biologics include phosphate, citric acid, acetic acid, tromethamine, histidine, arginine, gluconic acid, lactic acid, tartaric acid, aspartic acid, and glutamic acid.

[00136] Other buffers also may be found suitable or desirable in some circumstances, such as buffers based on HEPES (N42-hydroxyethylIpeperazine-N'42-ethanesulfonic acid}) having pKa of 7.5 at 25 C and pH in the range of about 6.8-8.2; BES (N,N-bis{2-hydroxyethy1}2-aminoethanesulfonic acid) having pKa of 7.1 at 25 C and pH in the range of about 6.4-7.8; MOPS (3{N-morpholino}propanesulfonic acid) having pKa of 7.2 at and pH in the range of about 6.5-7.9; TES (N-tristhydroxymethy1I-methyl-2-aminoethanesulfonic acid) having pKa of 7.4 at 25 C and pH in the range of about 6.8-8.2;
MOBS (4{N-morpholino}butanesulfonic acid) having pKa of 7.6 at 25 C and pH in the range of about 6.9-8.3; DIP 50 (3-(N,N-bis{2-hydroxyethyl}amino)-2-hydroxypropane) ) having pKa of 7.52 at 25 C and pH in the range of about 7-8.2; TAPSO (2-hydroxy-3{tris(hydroxymethyl)methylamino}-1-propanesulfonic acid) ) having pKa of 7.61 at 25 C
and pH in the range of about 7-8.2.

[00137] In certain embodiments, a composition of the present invention is formulated in a buffer having an acidic pH, such as from about 4 to about 6.8, or alternatively, from about 5 to about 6.8. In such embodiments, the buffer capacity of the composition desirably allows the composition to come rapidly to a physiological pH after being administered into the patient.

[00138] In addition to a buffer, a composition of the present invention can comprise a material selected from the group consisting of surfactants, stabilizers, preservatives, co-solvent, humectants, emollients, chelating agents, tonicity-adjusting agents, and antioxidants.

[00139] In one aspect, any of these materials that may be used in a composition of the present invention is a physiologically acceptable material. In certain embodiments, any of these materials that may be used in a composition of the present invention is an ophthalmically acceptable material.

[00140] Water-soluble preservatives that may be employed include quaternary ammonium compounds such as benzalkonium chloride and various polyquaternium compounds. These agents may be present in individual amounts of from about 0.001 to about 2% by weight (preferably, about 0.01% to about 0.05% by weight).

[00141] Non-limiting examples of surfactants include, but are not limited to, non-ionic surfactants, for example, polysorbates (such as polysorbate 20, polysorbate 80), 4-(1,1,3,3-tetramethylbutyl)phenol/poly(oxyethylene) polymers (such as the polymer sold under the trademark Tyloxapol), poly(oxyethylene)-poly(oxypropylene) block copolymers, glycolic esters of fatty acids and the like, and mixtures thereof.

[00142] In one aspect, the pH of the composition is in the range from about 4 to about 8.
Alternatively, the pH of the composition is in the range from about 6 to about 8, or from about 6.5 to about 8, or from about 6.5 to about 7.5.

[00143] In another aspect, the composition has a pH of about 7. Alternatively, the composition has a pH in a range from about 7 to about 7.5.

[00144] In still another aspect, the composition has a pH of about 7.4.

[00145] In yet another aspect, a composition also can comprise a viscosity-modifying compound designed to facilitate the administration of the composition into the subject or to promote the bioavailability in the subject. In still another aspect, the viscosity-modifying compound may be chosen so that the composition is not readily dispersed after being administered into an environment of an eye. Such compounds may enhance the viscosity of the composition, and include, but are not limited to: monomeric polyols, such as, glycerol, propylene glycol, ethylene glycol; polymeric polyols, such as, polyethylene glycol; various polymers of the cellulose family, such as hydroxypropylmethyl cellulose ("HPMC"), carboxymethyl cellulose ("CMC") sodium, hydroxypropyl cellulose ("HPC");
polysaccharides, such as hyaluronic acid and its salts, chondroitin sulfate and its salts, dextrans, such as, dextran 70; water soluble proteins, such as gelatin; vinyl polymers, such as, polyvinyl alcohol, polyvinylpyrrolidone, povidone; carbomers, such as carbomer 934P, carbomer 941, carbomer 940, or carbomer 974P; and acrylic acid polymers. In general, a desired viscosity can be in the range from about 1 to about 400 centipoises ("cps") or mPa.s.

[00146] Non-limiting examples of chelating agents include ethylenediaminetetraacetic acid ("EDTA"), diethylenetriaminepentakis(methylphosphonic acid), etidronic acid, tetrasodium salt of etidronic acid (also known as "HAP").

[00147] While the buffer itself is a "tonicity-adjusting agent" and a "pH-adjusting agent"
that broadly maintains the ophthalmic solution at a particular ion concentration and pH, additional "tonicity-adjusting agents" can be added to adjust the final tonicity of the solution.
Such tonicity-adjusting agents are well known to those of skill in the art and include, but are not limited to, mannitol, sorbitol, dextrose, sucrose, urea, propylene glycol, and glycerin.
Also, various salts, including halide salts of a monovalent cation (e.g., NaCl or KC1) can be utilized. Typically, the tonicity of a formulation of the present invention is in the range from about 200 to 400 mOsm/kg. Alternatively, the tonicity of a formulation of the present invention is in the range from about 220 to 400 mOsm/kg, or from about 220 to mOsm/kg, or from about 220 to 300 mOsm/kg, or from about 250 to 350 mOsm/kg.

[00148] Non-limiting examples of anti-oxidants include ascorbic acid (vitamin C) and its salts and esters; tocopherols (such as a-tocopherol) and tocotrienols (vitamin E), and their salts and esters (such as vitamin E TGPS (D-a-tocopheryl polyethylene glycol succinate)); glutathione; lipoic acid; uric acid; butylated hydroxyanisole ("BHA"); butylated hydroxytoluene ("BHT"); tertiary butylhydroquinone ("TBHQ"); and polyphenolic anti-oxidants (such as gallic acid, cinnanmic acid, flavonoids, and their salts, esters, and derivatives).

[00149] Non-limiting examples of stabilizers includes sucrose, mannitol, sorbitol, and trehalose.

[00150] It should be understood that the proportions of the various components or mixtures in the following examples may be adjusted for the appropriate circumstances.

[00151] In another aspect, an antibody fusion protein of the present invention and appropriate amounts of one or more desired excipients are incorporated into a formulation for topical administration or injection to a portion of the eye, such as the anterior or posterior segment, or the vitreous humor. An injectable formulation can desirably comprise a carrier that provides a sustained-release of the active ingredients, such as for a period longer than about 1 week (or longer than about 1, 2, 3, 4, 5, or 6 months). In certain embodiments, an antibody fusion protein of the present invention is included in a delivery device for sustained release of the active ingredients over a long period of time, such as 4, 5, 6 months or longer.
An example of such delivery device is described in U.S. Patents 8,399,006 and 9,417,238.

[00152] In still another aspect, a composition comprising an antibody fusion protein of the present invention and desired excipients is lyophilized and is reconstituted with a physiologically acceptable liquid carrier substantially immediately before administration to a subject.

[00153] In one embodiment, a compound or composition of the present invention can be injected with a fine-gauge needle, such as 25-35 gauge. Typically, an amount from about 25 pi to about 100 pi of a composition comprising about 25-4000 [ig of an antibody fusion protein of the present invention is administered into a patient. In one embodiment, the antibody fusion protein has heavy chain and light chain amino acid sequences substantially as listed in SEQ ID NO: 18 and 20; or SEQ ID NO: 22 and 24; or SEQ ID NO: 26 and 28; or SEQ ID NO: 30 and 32, or SEQ ID NO: 78 and 80; or SEQ ID NO: 82 and 84; or SEQ
ID
NO: 86 and 88; or SEQ ID NO: 90 and 100. In another embodiment, an antibody fusion protein used in such a procedure can comprise a pair or dimer of proteins having a sequence substantially as listed in SEQ ID NO: 60, 62, 64, 66, 74, or 76. In still another embodiment, an antibody fusion protein used in such a procedure can comprise a pair or dimer of proteins having a sequence that begins at amino acid 17 of the sequences substantially as listed in SEQ ID NO: 60, 62, 64, 66, 74, or 76. In yet another embodiment, the antibody fusion protein has heavy chain and light chain amino acid sequences as listed in SEQ
ID NO: 18 and 20; or SEQ ID NO: 22 and 24; or SEQ ID NO: 26 and 28; or SEQ ID NO: 30 and 32, or SEQ
ID NO: 78 and 80; or SEQ ID NO: 82 and 84; or SEQ ID NO: 86 and 88; or SEQ ID
NO: 90 and 100. In still another embodiment, an antibody fusion protein used in such a procedure can comprise a pair or dimer of proteins having a sequence that begins at amino acid 17 of the sequences as listed in SEQ ID NO: 60, 62, 64, 66, 74, or 76. A
concentration of such antibody fusion protein is selected from the ranges disclosed above.

[00154] In still another aspect, an antibody fusion protein of the present invention is incorporated into an ophthalmic device that comprises a biodegradable material, and the device is implanted into a posterior-segment tissue of a subject to provide along-term (e.g., longer than about 1 week, or longer than about 1, 2, 3, 4, 5, or 6 months) treatment or control of an angiogenic disease, condition, or disorder. Such a device may be implanted by a skilled physician in the subject's ocular or periocular tissue. Non-limiting examples of ophthalmic implant systems or devices for the sustained-release of an active ingredient are disclosed in U.S. Patents 5,378,475; 5,773,019; 5,902,598; 6,001,386; 6,051,576; and 6,726,918.

[00155] In still another aspect, a method for treating or controlling an ophthalmic angiogenic disease, condition, or disorder comprises administering a composition comprising an antibody fusion protein of the present invention to a subject in need thereof.

[00156] In still another aspect, an antibody fusion protein used in said method comprises an antibody against IL-6R or an antigen-binding fragment or domain thereof;
wherein at least one of: (1) a light chain or an antigen-binding fragment or domain thereof and (2) a heavy chain or an antigen-binding fragment or domain thereof is linked to a VEGF
binding unit that comprises: (1) (a) Ig-like domain 2, or substantially Ig-like domain 2, of human VEGFR-1;
and (b) Ig-like domain 3, or substantially Ig-like domain 3, of human VEGFR-2;
or (2) at least an Ig-like domain selected from the group consisting of Ig-like domains 1, 2, and 3, or substantially Ig-like domains 1, 2, and 3, of human VEGFR-3. In one embodiment, the VEGF binding unit comprises (a) Ig-like domains 1 and 2, or substantially Ig-like domains 1 and 2; or (b) Ig-like domains 2 and 3, or substantially Ig-like domains 2 and 3; or (c) Ig-like domains 1, 2, and 3, or substantially Ig-like domains 1, 2, and 3, of human VEGFR-3.

[00157] In still another aspect, a method for treating or controlling an ophthalmic angiogenic disease, condition, or disorder comprises administering a composition comprising an antibody fusion protein having heavy chain and light chain amino acid sequences as listed in SEQ ID NO: 18 and 20; or SEQ ID NO: 22 and 24; or SEQ ID NO: 26 and 28; SEQ
ID
NO: 30 and 32; SEQ ID NO: 78 and 80; SEQ ID NO: 82 and 84; SEQ ID NO: 86 and 88;
SEQ ID NO: 90 and 92; SEQ ID NO: 94 and 96; or SEQ ID NO: 98 and 100; or an antibody fusion protein having an amino acid sequence as listed in SEQ ID NO: 60, SEQ
ID NO: 62, SEQ ID NO: 64, SEQ ID NO: 66, SEQ ID NO: 74, or SEQ ID NO: 76 to a subject in need thereof. In still another aspect, an antibody fusion protein used in such a method can comprise a pair or dimer of proteins having a sequence that begins at amino acid 17 of the sequences as listed in SEQ ID NO: 60, 62, 64, 66, 74, or 76.

[00158] In still another aspect, a method for treating or controlling an ophthalmic angiogenic disease, condition, or disorder having an etiology in aberrant angiogenesis of in the posterior segment of an eye comprises intravitreally injecting a composition comprising an antibody fusion protein having heavy chain and light chain amino acid sequences as listed in SEQ ID NO: 18 and 20; or SEQ ID NO: 22 and 24; or SEQ ID NO: 26 and 28; or SEQ ID
NO: 30 and 32; SEQ ID NO: 78 and 80; SEQ ID NO: 82 and 84; SEQ ID NO: 86 and 88;
SEQ ID NO: 90 and 92; SEQ ID NO: 94 and 96; or SEQ ID NO: 98 and 100; or an antibody fusion protein having an amino acid sequence as listed in SEQ ID NO: 60, SEQ
ID NO: 62, SEQ ID NO: 64, SEQ ID NO: 66, SEQ ID NO: 74, or SEQ ID NO: 76 to a subject in need thereof. In still another aspect, an antibody fusion protein used in such a method can comprise a pair or dimer of proteins having a sequence that begins at amino acid 17 of the sequences as listed in SEQ ID NO: 60, 62, 64, 66, 74, or 76.

[00159] In another embodiment, such disease, condition, or disorder is selected from the group consisting of: choroidal neovascularization including neovascular age-related macular degeneration (wet age-related macular degeneration), polypoidal choroidal vasculopathy (PCV) and myopic choroidal neovacular degeneration, vascular leak, macular edema resulting from diabetes, uveitis, central and branch retinal vein occlusion, non-proliferative and proliferative diabetic retinopathy, retinopathy of prematurity, corneal neovascularization, corneal inflammation, and neovascular glaucoma.

[00160] In yet another aspect, a composition of the present invention is administered once a week, once a month, once a year, twice a year, four times a year, or at a suitable frequency that is determined to be appropriate for treating or controlling an anterior-segment inflammatory disease, condition, or disorder.

[00161] In still another aspect, an antibody fusion protein of the present invention can also be used for the treatment or control of tumors, systemic inflammatory diseases or conditions, or autoimmune diseases such as arthritis. Such treatment or control may be effected by, for example, systemic administration. Dosages and regimens for treating such diseases or conditions may be determined or recommended for the particular disease or condition by medical practitioners.
EXAMPLE 1: Antibody Fusion Proteins Comprising VEGFR-1-D2, VEGFR-2-D3, and a Monoclonal Antibody (mAb) against IL-6R.

[00162] Six antibody fusion proteins of the present invention were produced according to a method disclosed herein, denoted as B781401, B781402, B781403, B781404, B781405, and B781406.

[00163] B781401 consists of a VEGF-binding unit that consists of VEGFR-1-D2-VEGFR-2-D3 linked directly to the amino terminus of the heavy chain of tocilizumab (an mAb against IL-6R). The heavy chain of B781401 has the amino acid sequence SEQ
ID NO:
78, and the nucleic acid sequence SEQ ID NO: 79. The light chain of B781401 has the amino acid sequence SEQ ID NO: 80, and the nucleic acid sequence SEQ ID NO:
81.

[00164] Each of B781402, B781403, and B781404 consists of a VEGF-binding unit that consists of VEGFR-1-D2-VEGFR-2-D3 linked through a flexible linker to the amino terminus of the heavy chain of tocilizumab. The heavy chains of B781402, B781403, and B781404 have the amino acid sequences SEQ ID NO: 82, SEQ ID NO: 86, and SEQ ID
NO:
90, respectively; and the nucleic acid sequences SEQ ID NO:83, SEQ ID NO:87, and SEQ ID
NO: 91, respectively. The light chains of B781402, B781403, and B781404 have the amino acid sequence SEQ ID NO: 84, SEQ ID NO: 88, and SEQ ID NO: 92, respectively, and the nucleic acid sequences SEQ ID NO: 85, SEQ ID NO: 89, and SEQ ID NO: 93, respectively.

[00165] B781405 consists of a VEGF-binding unit that consists of VEGFR-1-D2-VEGFR-2-D3 linked directly to the amino terminus of the light chain of tocilizumab. The heavy chain of B781405 has the amino acid sequence SEQ ID NO: 94, and the nucleic acid sequence SEQ ID NO: 95. The light chain of B781405 has the amino acid sequence SEQ ID
NO: 96, and the nucleic acid sequence SEQ ID NO: 97.

[00166] B781406 consists of a VEGF-binding unit that consists of VEGFR-1-D2-VEGFR-2-D3 linked through a flexible linker to the amino terminus of the light chain of tocilizumab. The heavy chain of B781406 has the amino acid sequence SEQ ID NO:
98, and the nucleic acid sequence SEQ ID NO: 99. The light chain of B781406 has the amino acid sequence SEQ ID NO: 100, and the nucleic acid sequence SEQ ID NO: 101.

[00167] The carboxy terminus of the heavy chain of B781401, B781402, B781405, and B781406 has no glycine and lysine amino acid residues. The carboxy terminus of the heavy chain of B781404 has no lysine amino acid residue. The carboxy terminus of the heavy chain of B781403 includes glycine and lysine amino acid residues.

[00168] Figures 7A-D show schematic diagrams of antibody fusion proteins 781406.
EXAMPLE 2: Antibody Fusion Proteins Comprising IL-6R Binding scFv Linked to VEGFR-

[00169] Four antibody fusion proteins of the present invention were produced according to a method disclosed herein, denoted as EB-DJ1, EB-vvA, EB-vvB, EB-vvC.
Each of these fusion proteins comprises a pair of or a dimer of constructs, each of which comprises an IL-6R scFv, a Fc domain of IgGl, and a VEGF-binding unit that comprises human VEGFR-1-D2 and human VEGFR-2-D3. Specifically, each of EB-DJ1 and EB-vvA

consists of a dimer of constructs, each of which consists of an IL-6R scFv linked to a Fc domain of IgGl. The carboxy terminus of the IgGl-Fc domain is linked through a flexible linker to a VEGF-binding unit that consists of VEGFR-1-D2-VEGFR-2-D3. A
construct of EB-DJ1 has the amino acid sequence SEQ ID NO: 60 and the nucleic acid sequence SEQ ID
NO: 59. A construct of EB-vvA has the amino acid sequence SEQ ID NO: 74 and the nucleic acid sequence SEQ ID NO: 75.

[00170] EB-vvB consists of a dimer of constructs, each of which consists of an IL-6R
scFv linked through a flexible linker to a VEGF-binding unit that consists of VEGFR-2-D3. The carboxy terminus of the VEGF-binding unit is linked directly to the IgGl-Fc domain. A construct of EB-vvB has the amino acid sequence SEQ ID NO:
62 and the nucleic acid sequence SEQ ID NO: 61.

[00171] EB-vvC consists of a dimer of constructs, each of which consists of a VEGF-binding unit that consists of VEGFR-1-D2-VEGFR-2-D3 that is linked directly to the IgGl-Fc domain. The carboxy terminus of the IgGl-Fc domain is linked through a flexible linker to an IL-6R scFv. A construct of EB-vvC has the amino acid sequence SEQ ID NO:
76 and the nucleic acid sequence SEQ ID NO: 77.
EXAMPLE 2: Comparison of the ELISA Binding Affinities of EB-DJ1, EB-vvA, EB-vvB, and EB-vvC with Aflibercept, B781403 and B781405 for recombinant human VEGF-A165.

[00172]
Figure 8 shows schematic diagrams of antibody fusion proteins EB-DJ1, EB-vvA, EB-vvB, and EB-vvC.
EXAMPLE 3: Transient Expression and Purification of B781401-781406.

[00173] Genes encoding the amino acid sequences of B781401-781406 as indicated by the SEQ ID NO: 79,81, 83, 85, 87, 89, 91, 93, 95, 97, 99, and 101 were synthetized and expression vectors based on the vector pcDNA3.4 for expressing the proteins were constructed. The expression vectors were used to transiently transfect HEK293 cells with chemically defined culture media. The produced proteins were purified by Protein-A affinity column, ultrafiltration and then subjected to 0.21.tm sterile filtration to get the bulk of high purity proteins. Expression of B781401-781406 in HEK293 cells produced proteins with a 1\4W ¨200KDa (non-reduced form at SDS-PAGE) with ¨100% purity when analyzed by SEC-HPLC. SEC-HPLC chromatogram for B781401 is shown in Fig. 9. The results for the expression and purification of B781401-781406 are shown in Table 3.

Table 3 Expression and Purification of B781401-78140, Produced in HEK293 Cells Total protein Purity Purity Theoretical Theoretical Molecule Endotoxin ID (EU/m yield measured by measured g) molecular weight molecular weight (mg/100m1) SEC at 280nm SDS-PAGE
(reducing, KDa) (non-reducing, KDa) B781401 4.56 100% >95% <1 72/23 190 B781402 5.25 100% >95% <1 73/23 192 B781403 4.80 100% >95% <1 74/23 194 B781404 5.08 100% >95% <1 73/23 192 B781405 13.29 100% >95% <1 49/47 192 B781406 13.74 100% >95% <1 49/48 194

[00174] Genes encoding the amino acid sequences of B781401-781406 as indicated by the SEQ ID NO: 79,81, 83, 85, 87, 89, 91, 93, 95, 97, 99, and 101 were synthetized and expression vectors based on the vector pcDNA3.4 for expressing the proteins were constructed. The expression vectors were used to transiently transfect CHO
cells with chemically defined culture media. The produced proteins were purified by Protein-A affinity column, ultrafiltration and then subjected to 0.21.tm sterile filtration to get the bulk of high purity proteins. Expression of B781401-781406 in CHO cells produced proteins with a 1\4W
¨200KDa (non-reduced form at SDS-PAGE) with ¨93% purity when analyzed by SEC-HPLC. SEC-HPLC chromatogram for B781401 is shown in Fig. 10. The results for the expression and purification of B781401-781406 are shown in Table 4.
Table 4 Expression and Purification of B781401-78140, Produced in CHO Cells Purity Theoretical Total protein PuritY
Molecule measured by Endotoxi Theoretical n i molecular weight yield measured molecular weight ID SEC at (EU/mg) (non-reducing, (mg/100m1) SDS-PAGE (reducing, KDa) 280nm KDa) B781401 30.22 90.3% >95% <1 72/23 190 B781402 24.62 93.0% >95% <1 73/23 192 B781403 26.68 94.8% >95% <1 74/23 194 B781404 22.68 95.2% >95% <1 73/23 192 B781405 33.47 94.2% >95% <1 49/47 192 B781406 26.63 90.3% >95% <1 49/48 194 EXAMPLE 4: Comparison of the Binding Affinities of B781401-781406 with Aflibercept (Eylea ) for Recombinant Human VEGF-A165 Using Enzyme Linked Immunosorbent Assay (ELISA).

[00175] ELISA assays were performed using 96-well plates coated with recombinant human VEGF-A165 (2[tg/ml, 100 1/well) at +4 C for 16 hours. After non-specific blocking using 1% BSA at 25 C for 1 hour, a series of dilutions of test antibodies were added into the coated wells and incubated at 25 C for 1 hour. The bound Abs were detected using a secondary Ab (goat anti-human IgGl-Fc) conjugated with HRP followed by 0D450 reading.
The binding affinities of B781401-781406 for recombinant human VEGF-A165 are at sub-nanomolar scales and comparable with aflibercept. The results are shown in Fig.11.
EXAMPLE 5: Comparison of the ELISA Binding Affinities of B781401-781406 with Aflibercept for Recombinant Human VEGF-B167.

[00176] ELISA assays were performed using 96-well plates coated with recombinant human VEGF-B167 (2[tg/ml, 100[tl/well) at +4 C for 16 hours. After non-specific blocking using 1% BSA at 25 C for 1 hour, a series of dilutions of test antibodies were added into the coated wells and incubated at 25 C for 1 hour. The bound Abs were detected using a secondary Ab (goat anti-human IgGl-Fc) conjugated with HRP followed by 0D450 reading.
The binding affinities of B781401-781406 for recombinant human VEGF-A165 are at sub-nanomolar scales and comparable with aflibercept. The results are shown in Fig. 12.
EXAMPLE 6: Comparison of the ELISA binding affinities of B781401-781406 with aflibercept for recombinant human P1GF.

[00177] ELISA assays were performed using 96-well plates coated with recombinant human P1GF (2[tg/ml, 100[tl/well) at +4 C for 16 hours. After non-specific blocking using 1% BSA at 25 C for 1 hour, a series of dilutions of test antibodies were added into the coated wells and incubated at 25 C for 1 hour. The bound Abs were detected using a secondary Ab (goat anti-human IgGl-Fc) conjugated with HRP followed by 0D450 reading. The binding affinities of B781401-781406 for recombinant human P1GF are at sub-nanomolar scales and comparable with aflibercept. The results are shown in Fig. 13.

EXAMPLE 7: Comparison of the ELISA Binding Affinities of B781401-781406 with Tocilizumab for Recombinant Human IL-6R.

[00178] ELISA assays were performed using 96-well plates coated with recombinant human IL-6R (2 g/ml, 100W/well) at +4 C for 16 hours. After non-specific blocking using 1% BSA at 25 C for 1 hour, a series of dilutions of test antibodies were added into IL-6R-coated wells and incubated at 25 C for 1 hour. The bound Abs were detected using a secondary Ab (goat anti-human IgGl-Fc) conjugated with HRP followed by 0D450 reading.
The binding affinities of B781401-781406 for recombinant human IL-6R are at sub-nanomolar scales and comparable with tocilizumab. The results are shown in Fig. 17.
EXAMPLE 8: Comparison of the Effect of B781401-781406 with Aflibercept on Inhibiting VEGF-A165-Mediated VEGFR2 Signaling in VEGFR2-NFAT-RE Luciferase Reporter Cells.

[00179] Recombinant human VEGF-A165 were mixed with serial dilutions of test Abs, incubated at room temperature for 30 minutes, and then added into wells containing 4 x104 VEGFR2 (KDR)-NFAT-RE luciferase reporter cells/well followed by an incubation at 37 C
for 6 hours. Luciferase signal was detected by a plate reader after addition of 50p1 of Bright-Lite. Validation of VEGFR2 signaling luciferase assay using Bevacizumab (Avastin) as a positive control (see Fig. 15A). The effects of B781401-781406 on inhibiting mediated VEGFR2 signaling are comparable to aflibercept (see Fig. 15B).
EXAMPLE 9: Comparison of the Effect of B781401-781406 with Tocilizumab on Inhibiting IL-6R Signaling.

[00180] Measurement of phosphorylation of Signal Transducer and Activator of Transcription 3 (STAT3) was conducted in TF-1 cells in response to recombinant stimuation using a phospho-STAT3 (Tyr705) cellular kit from Cisbio according to the manufacturer's instructions. Detection of phosphorylated STAT3 involves a sandwich immunoassay which includes an anti-phospho STAT3 antibody coupled with an anti-total antibody labeled with eitherdonor or acceptor fluors. Activation of the IL-6/IL-6R signaling in TF-1 cells causes an increase in Homogeneous Time Resolved Fluorescence (HTRF) signal, whereas inhibition will demonstrate the opposite effect. B781401, B781402, B781404, and B781405 showed comparable effects with tocilizumab on inhibiting phosphorylation of STAT3 in TF-1 cells stimulated by recombinant human IL-6 ligand. The results are shown in Fig. 16.
EXAMPLE 10: Comparison of the Effect of B781401-781406 with Siltuximab and Tocilizumab on Inhibiting IL-6R Signaling.

[00181] Measurement of IL-6 mediated TF-1 cell proliferation was conducted using CellTiter-Glo Luminescent Cell Viability Assay with a kit obtained from Promega according to the manufacturer's instructions. Activation of IL-6R signaling in TF-1 cells results in TF-1 cell proliferation which is reflected by increased luminescent signal, whereas inhibition of IL-6R signaling will demonstrate the opposite effect. B781404, B781405, and B781406 showed comparable effects on inhibiting TF-1 cell proliferation stimulated by recombinant human IL-6 ligand. Siltuximab is a mAb against IL-6. The results are shown in Fig. 17.

[00182] A summary of the profiles of B781401-781406 is shown in Table 5 for the transient expression in HEK293 and CHO cells, ELISA binding affinities for human VEGF-A165, VEGF-B167, P1GF, and IL-6R, as well as inhibition in three cell-based functional assays Table 5 Summary of the Profiles of B781401-781406 Expression Level Ligand Binding Affinity In Vifro Functional Evaluation Molecule (mg per 100 ml) (EC50, nM) (IC50, nM) HEK293 CHO P1GF IL-6R . P-STAT3 . .
A165 B 167 Luciferase Proliferation B781401 4.56 30.22 0.077 0.124 0.116 1.787 0.198 7.705 2.381 B781402 5.25 24.62 0.085 0.115 0.108 1.035 0.183 3.398 1.623 B781403 4.80 26.68 0.049 0.060 0.288 0.639 0.213 23.990 1.302 B781404 5.08 22.68 0.142 0.157 0.448 1.709 0.172 4.908 0.874 B781405 13.29 33.47 0.033 0.059 0.026 0.505 0.160 0.938 0.417 B781406 13.74 26.63 0.050 0.061 0.131 2.121 0.187 11.515 0.904 Aflibercep N/A N/A 0.034 0.865 0.281 N/A 0.113 N/A N/A
Tocilizum N/A N/A N/A N/A N/A 0.476 N/A 3.87/3.84 0.215 ab EXAMPLE 11: Comparison of the ELISA Binding Affinities of EB-DJ1, EB-vvA, EB-vvB, and EB-vvC with Aflibercept, B781403, and B781405 for Recombinant Human VEGF-A165.

[00183] ELISA assays were performed using 96-well plates coated with recombinant human VEGF-A165 (2 g/ml, 100W/well) at +4 C for 16 hours. After non-specific blocking using 1% BSA at 25 C for 1 hour, a series of dilutions of test antibodies were added into the coated wells and incubated at 25 C for 1 hour. The bound Abs were detected using a secondary Ab (goat anti-human IgGl-Fc) conjugated with HRP followed by 0D450 reading.
The binding affinities of EB-DJ1, EB-vvA, EB-vvB, and EB-vvC for recombinant human VEGF-A165 are at sub-nanomolar scales and comparable with aflibercept, B781403 and B781405. The results are shown in Fig. 18.
EXAMPLE 12: Comparison of the ELISA Binding Affinities of EB-DJ1, EB-vvA, EB-vvB, and EB-vvC with Aflibercept, B781402, B781403, and B781405 for Recombinant Human VEGF-B167.

[00184] ELISA assays were performed using 96-well plates coated with recombinant human VEGF-B167 (2 g/ml, 100W/well) at +4 C for 16 hours. After non-specific blocking using 1% BSA at 25 C for 1 hour, a series of dilutions of test antibodies were added into VEGF-B167-coated wells and incubated at 25 C for 1 hour. The bound Abs were detected using a secondary Ab (goat anti-human IgGl-Fc) conjugated with HRP followed by reading. The binding affinities of EB-DJ1, EB-vvA, EB-vvB, and EB-vvC for recombinant human VEGF-B167 are at sub-nanomolar scales and comparable with aflibercept, B781402, B781403, and B781405. The results are shown in Fig. 19.
EXAMPLE 13: Comparison of the ELISA Binding Affinities of EB-DJ1, EB-vvA, EB-vvB, and EB-vvC with Aflibercept, B781403, and B781405 for Recombinant Human P1GF.

[00185] ELISA assays were performed using 96-well plates coated with recombinant human P1GF (2 g/ml, 100W/well) at +4 C for 16 hours. After non-specific blocking using 1% BSA at 25 C for 1 hour, a series of diluted test antibodies were added into the coated wells and incubated at 25 C for 1 hour. The bound Abs were detected using a secondary Ab (goat anti-human IgGl-Fc) conjugated with HRP followed by 0D450 reading. The binding affinities of EB-DJ1, EB-vvA, EB-vvB and EB-vvC for recombinant human P1GF are at sub-nanomolar scales and comparable with aflibercept, B781403 and B781405. The results are shown in Fig. 20.

[00186] EXAMPLE 14: Comparison of the ELISA Binding Affinities of EB-DJI, EB-vvA, EB-vvB, and EB-vvC with Tocilizumab, B781402, B781403, and B781405 for Recombinant Human IL-6R.

[00187] ELISA assays were performed using 96-well plates coated with recombinant human IL-6R (2 g/ml, 100 1/well) at +4 C for 16 hours. After non-specific blocking using 1% BSA at 25 C for 1 hour, a series of dilutions of test antibodies were added into I1-6R-coated wells and incubated at 25 C for 1 hour. The bound Abs were detected using a secondary Ab (goat anti-human IgGl-Fc) conjugated with HRP followed by 0D450 reading.
The binding affinities of EB-DJI, EB-vvA, EB-vvB, and EB-vvC for recombinant human IL-6R are at sub-nanomolar scales and comparable with tocilizumab, B781402, B781403 and B781405. The results are shown in Fig. 21.

[00188] A summary of the profiles of EB-DJI, EB-vvA, EB-vvB, and EB-vvC in their binding affinities for human VEGF-A165, VEGF-B167, P1GF and IL-6R is shown in Table 6 Table 6 Summary of the Profiles of EB-DJI, EB-vvA, EB-vvB, and EB-vvC
Ligand Binding Affinity Yield in (EC50, nM) Molecule HEK293 cells (111g/L) VEGF-A165 VEGF-B167 131GF IL-6R
EB-DJ1 13.2 0.1722 2.6950 0.6845 0.0654 EB-vvA 17.9 0.2793 0.9110 0.9250 0.0504 EB-vvB 24.0 0.2046 0.3643 0.7140 0.0416 EB-vvC 13.2 0.2516 2.1875 0.3049 0.3847 B781402 52.5 Not Done 0.3130 Not Done 0.1862 B781403 48.0 0.3071 0.1379 0.9747 0.0432 B781405 132.9 0.1940 0.0766 0.3071 0.1707 Aflibercept N/A 0.2407 0.0697 3.4649 N/A
Tocilizumab N/A N/A N/A N/A 0.0547 NUCLEIC ACID AND AMINO ACID SEQUENCE LISTING

[00189] CAG GTG CAG CTG CAG GAA TCA GGG CCT GGT TTG GTG CGG CCG
AGT CAG ACG CTC AGC TTG ACT TGT ACG GTG TCA GGT TAC TCT ATC ACT
AGC GAT CAT GCC TGG AGC TGG GTA CGA CAA CCA CCG GGT CGG GGT CTC
GAA TGG ATA GGT TAC ATA AGC TAC TCA GGA ATC ACG ACA TAC AAT CCC
TCC CTT AAA AGT CGG GTC ACC ATG CTC CGA GAC ACT AGT AAA AAT CAG
TTC TCC CTG CGG TTG TCC AGC GTG ACT GCT GCC GAC ACG GCG GTC TAT
TAT TGC GCA AGA AGT CTG GCG CGG ACA ACG GCA ATG GAC TAC TGG GGA
CAA GGT TCA CTG GTA ACC GTT AGT TCA GCA AGC ACC AAG GGT CCG TCT
GTC TTT CCA CTC GCG CCT TCT AGC AAG TCA ACC TCA GGG GGG ACT GCC
GCG CTT GGA TGT CTG GTC AAA GAT TAT TTT CCT GAG CCG GTA ACA GTT
AGC TGG AAT TCA GGT GCC CTC ACA TCT GGG GTA CAC ACG TTT CCC GCC
GTG CTT CAG AGC TCT GGC CTC TAC AGT CTT TCT AGC GTG GTC ACC GTC
CCA TCT TCA TCA TTG GGT ACA CAA ACT TAC ATT TGT AAC GTT AAT CAC
AAA CCT AGC AAC ACT AAG GTG GAT AAA AAA GTA GAG CCA AAG TCC TGC
GAC AAG ACT CAC ACC TGT CCT CCC TGT CCA GCA CCC GAA CTT TTG GGC
GGT CCT TCT GTT TTC CTG TTT CCT CCT AAA CCC AAA GAT ACA CTC ATG
ATC TCC AGA ACC CCG GAA GTA ACC TGC GTA GTC GTG GAC GTA TCC CAT
GAG GAT CCC GAG GTA AAA TTC AAC TGG TAC GTA GAC GGG GTC GAG GTG
CAC AAT GCC AAG ACT AAA CCT AGG GAA GAG CAA TAC AAT AGT ACG TAC
AGG GTG GTT TCC GTG CTG ACC GTC CTG CAT CAG GAT TGG CTC AAC GGG
AAA GAG TAT AAA TGT AAG GTG TCA AAC AAA GCT TTG CCG GCA CCA ATA
GAG AAA ACC ATT AGT AAG GCG AAA GGA CAA CCC CGA GAG CCA CAA GTG
TAT ACG TTG CCT CCC AGC CGC GAG GAA ATG ACG AAG AAT CAA GTC TCT
CTG ACT TGT CTG GTG AAG GGT TTT TAC CCG TCT GAT ATA GCT GTC GAA
TGG GAG TCT AAC GGC CAG CCA GAG AAT AAT TAC AAA ACC ACT CCT CCG
GTC TTG GAT TCT GAT GGG AGC TTT TTC CTG TAT TCC AAA TTG ACA GTT
GAT AAA AGT CGG TGG CAG CAG GGG AAC GTC TTC TCC TGT AGC GTC ATG
CAT GAA GCA CTG CAT AAT CAT TAT ACC CAA AAA AGT TTG TCC TTG AGC
CCT GGT
(SEQ ID NO: 1) [00 1 90] QVQLQESGPGLVRPSQTLSLTCTVSGYSITSDHAWSWVRQPPGRGLEWIG
YISYSGITTYNPSLKSRVFMLIWTSKNQF SLRLSSVTAADTAVYYC ARSLARTTAMD
YWGQGSLVTVS SAS TKGP SVFPLAPS SK STSGGTAALGCLVKD YFPEPVF VS WN SCiA
LT SGVHTFPAVLQ S S GLY SLS S VVT VP S S SLGTQTYICNVNHKP SNTKVDKKVEPK SC
D K THITCP PC PAPELLGGPS VIII PP KP Kai:LA/HS:MT E VTCVVVDVSHEDPEVICFNWY
VDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIE
KTISKAKGQPREPQ VYTLPP SREEMIKNQVS:1_,TCUVI(GT YP SDIAVEW ESNWPENN
YKTTITVLDSDGSFFLYSKLINDICSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG
(SEQ ID NO: 2) [00191] GAC ATT CAA ATG ACT CAG TCT CCA TCC AGT CTC TCC GCT TCT
GTG GGG GAC CGA GTA ACC ATA ACA TGT CGG GCA TCT CAG GAC ATA AGC
TCA TAC TTG AAT TGG TAT CAG CAG AAA CCA GGG AAG GCG CCC AAG CTT
CTT ATC TAC TAT ACA TCA AGA CTT CAT AGC GGG GTG CCA AGC CGA TTC
AGT GGC AGC GGT TCA GGA ACA GAC TTT ACG TTC ACC ATT TCA TCT TTG
CAG CCA GAA GAT ATA GCT ACG TAC TAC TGT CAG CAA GGA AAT ACG TTG
CCG TAC ACC TTT GGC CAG GGC ACA AAA GTC GAA ATT AAG CGA ACC GTA
GCA GCC CCG AGT GTC TTT ATC TTT CCT CCC TCA GAT GAG CAA CTT AAA
AGC GGG ACA GCC TCA GTA GTT TGC CTC CTG AAC AAT TTC TAC CCA CGG
GAA GCC AAG GTG CAG TGG AAG GTG GAC AAT GCT CTT CAG TCC GGC AAC
TCT CAG GAA AGT GTT ACC GAG CAA GAC TCT AAA GAC TCA ACT TAC AGC
CTC AGC TCC ACC CTC ACT TTG TCC AAG GCT GAT TAC GAA AAA CAT AAG
GTA TAT GCC TGC GAA GTT ACG CAC CAA GGA CTT TCA TCC CCG GTG ACA
AAG AGC TTC AAC AGA GGC GAA TGT
(SEQ ID NO: 3) [00192] DIQMTQSPSSLSASVGDRVFITCRASQDISSYLNWYQQKPGKAPKLLIYYT
SRLIISGNIPSRFSGSGSGTDFTFTISSUPEDIATYYCQQGNIL,PYTFGQG-TKVEIKRTV
AAF'SVFIFPPSDEQLK SCiTASVVCLLNNFYPREAKVQWKVDNALQ SGNSQESVTEQD
SKDSTYSLSSTLILSKADYEKIIKVYACEVIIIQGL,SSPVTKSFNRGEC
(SEQ ID NO: 4) [00193] TCC GAC ACA GGA CGC CCC TTC GTA GAA ATG TAC TCT GAG ATT
CCG GAA ATC ATC CAT ATG ACT GAG GGC AGA GAG TTG GTC ATA CCA TGC

AGA GTC ACT TCA CCA AAT ATA ACC GTG ACG TTG AAG AAA TTT CCC TTG
GAC ACG TTG ATT CCC GAT GGT AAG CGG ATT ATA TGG GAC AGC CGC AAG
GGC TTT ATA ATA AGT AAT GCA ACA TAT AAG GAA ATA GGT CTC CTC ACA
TGC GAA GCT ACA GTC AAC GGC CAT CTC TAC AAG ACA AAT TAT CTT ACC
CAC AGG CAG ACG AAC ACA ATA ATT
(SEQ ID NO: 5) [00194] SD TGRPFVEMY SEIPEIIHMTEGRELVIP CRVT SPNITVTLKKFPLDTLIPDG
KRIIWDSRKGFIISNATYKEIGLLTCEATVNGHLYKTNYLTHRQTNTII
(SEQ ID NO: 6) [00195] GAC GTG GTT CTT TCA CCC TCA CAC GGT ATT GAG TTG TCA GTC
GGT GAG AAG CTG GTC TTG AAC TGC ACG GCC AGA ACG GAA TTG AAC GTC
GGC ATT GAT TTT AAC TGG GAA TAC CCG TCC TCT AAA CAC CAA CAC AAG
AAG TTG GTC AAC CGC GAT CTG AAG ACC CAA TCC GGA AGT GAA ATG AAG
AAA TTC TTG TCT ACT TTG ACC ATT GAT GGC GTC ACG AGA TCT GAT CAA
GGG CTT TAC ACC TGC GCC GCG AGC TCT GGT CTT ATG ACC AAG AAG AAC
AGT ACA TTT GTG CGG GTA CAT GAA AAA
(SEQ ID NO: 7) [00196] DVVL SP SHGIELSVGEKLVLNCTARTELNVGIDFNWEYP SSKHQHKKLVN
RDLKTQSGSEMKKFL S TLTID GVTR SD Q GLYT CAA S SGLMTKKNSTFVRVHEK
(SEQ ID NO: 8) [00197] TAT TCT ATG ACA CCG CCG ACC TTG AAC ATA ACC GAG GAA TCA
CAT GTA ATA GAC ACA GGG GAC TCA CTT TCA ATC AGC TGT CGA GGC CAG
CAC CCC CTG GAA TGG GCT TGG CCG GGG GCA CAA GAA GCA CCT GCT ACT
GGT GAC AAG GAC AGC GAA GAT ACG GGA GTA GTT AGA GAC TGT GAG GGC
ACA GAC GCT AGA CCT TAC TGC AAG GTC CTG CTT TTG CAT GAA GTG CAC
GCT AAC GAC ACT GGG AGC TAT GTC TGC TAC TAC AAG TAT ATC AAA GCG
CGG ATA GAG GGA ACG ACA GCT GCG TCA AGT TAT GTG TTC GTC AGA GAT
TTT GAG CAA CCG TTT ATT AAT AAG CCT GAC ACG CTG CTT GTA AAT AGA
AAA GAC GCC ATG TGG GTA CCA TGT CTG GTC AGT ATA CCT GGT CTC AAT
GTG ACT CTT CGC TCT CAA AGC AGC GTG CTG TGG CCG GAC GGC CAG GAA

GTG GTT TGG GAT GAC AGG CGG GGG ATG CTT GTT TCC ACT CCG CTT CTC
CAT GAC GCC CTC TAC CTG CAA TGT GAA ACC ACG TGG GGT GAT CAA GAT
TTC CTG TCT AAT CCC TTC TTG GTA CAT ATC ACC GGG AAC GAA CTC
(SEQ ID NO: 9) [00198] YSMTPPTLNITEESHVIDTGDSLSISCRGQHPLEWAWPGAQEAPATGDKD
SEDTGVVRDCEGTDARPYCKVLLLHEVHANDTGSYVCYYKYIKARIEGTTAASSYV
FVRDFEQPFINKPDTLLVNRKDAMWVPCLVSIPGLNVTLRSQSSVLWPDGQEVVWD
DRRGMLVSTPLLHDALYLQCETTWGDQDFLSNPFLVHITGNEL
(SEQ ID NO:10) [00199] GGA GAA GGT TCC GGT GAT GGA GGT GAG GGG AGC GGG GAT GGG
GAA GGT (SEQ ID NO:11) [00200] GEGSGDGGE GSGDGEG (SEQ ID NO: 12) [00201] GGA GGC TCA GGT GGC GGT GGT TCT GGC GGA GGA
(SEQ ID NO: 13) [00202] GGSGGG GSGGG (SEQ ID NO: 14) [00203] ATG CCG TTG CTG CTG CTT TTG CCA CTC CTT TGG GCC GGG GCT
TTG GCA (SEQ ID NO: 15) [00204] MPLLLLLPLLWAGALA (SEQ ID NO: 16) [00205] ATG CCT CTC CTC CTC CTC TTG CCC CTC CTT TGG GCC GGA GCC
CTG GCT CAG GTG CAG CTG CAG GAA TCA GGG CCT GGT TTG GTG CGG CCG
AGT CAG ACG CTC AGC TTG ACT TGT ACG GTG TCA GGT TAC TCT ATC ACT
AGC GAT CAT GCC TGG AGC TGG GTA CGA CAA CCA CCG GGT CGG GGT CTC
GAA TGG ATA GGT TAC ATA AGC TAC TCA GGA ATC ACG ACA TAC AAT CCC
TCC CTT AAA AGT CGG GTC ACC ATG CTC CGA GAC ACT AGT AAA AAT CAG
TTC TCC CTG CGG TTG TCC AGC GTG ACT GCT GCC GAC ACG GCG GTC TAT
TAT TGC GCA AGA AGT CTG GCG CGG ACA ACG GCA ATG GAC TAC TGG GGA
CAA GGT TCA CTG GTA ACC GTT AGT TCA GCA AGC ACC AAG GGT CCG TCT

GTC TTT CCA CTC GCG CCT TCT AGC AAG TCA ACC TCA GGG GGG ACT GCC
GCG CTT GGA TGT CTG GTC AAA GAT TAT TTT CCT GAG CCG GTA ACA GTT
AGC TGG AAT TCA GGT GCC CTC ACA TCT GGG GTA CAC ACG TTT CCC GCC
GTG CTT CAG AGC TCT GGC CTC TAC AGT CTT TCT AGC GTG GTC ACC GTC
CCA TCT TCA TCA TTG GGT ACA CAA ACT TAC ATT TGT AAC GTT AAT CAC
AAA CCT AGC AAC ACT AAG GTG GAT AAA AAA GTA GAG CCA AAG TCC TGC
GAC AAG ACT CAC ACC TGT CCT CCC TGT CCA GCA CCC GAA CTT TTG GGC
GGT CCT TCT GTT TTC CTG TTT CCT CCT AAA CCC AAA GAT ACA CTC ATG
ATC TCC AGA ACC CCG GAA GTA ACC TGC GTA GTC GTG GAC GTA TCC CAT
GAG GAT CCC GAG GTA AAA TTC AAC TGG TAC GTA GAC GGG GTC GAG GTG
CAC AAT GCC AAG ACT AAA CCT AGG GAA GAG CAA TAC AAT AGT ACG TAC
AGG GTG GTT TCC GTG CTG ACC GTC CTG CAT CAG GAT TGG CTC AAC GGG
AAA GAG TAT AAA TGT AAG GTG TCA AAC AAA GCT TTG CCG GCA CCA ATA
GAG AAA ACC ATT AGT AAG GCG AAA GGA CAA CCC CGA GAG CCA CAA GTG
TAT ACG TTG CCT CCC AGC CGC GAG GAA ATG ACG AAG AAT CAA GTC TCT
CTG ACT TGT CTG GTG AAG GGT TTT TAC CCG TCT GAT ATA GCT GTC GAA
TGG GAG TCT AAC GGC CAG CCA GAG AAT AAT TAC AAA ACC ACT CCT CCG
GTC TTG GAT TCT GAT GGG AGC TTT TTC CTG TAT TCC AAA TTG ACA GTT
GAT AAA AGT CGG TGG CAG CAG GGG AAC GTC TTC TCC TGT AGC GTC ATG
CAT GAA GCA CTG CAT AAT CAT TAT ACC CAA AAA AGT TTG TCC TTG AGC
CCT GGT GGC GAG GGT TCA GGG GAT GGA GGC GAG GGG TCC GGG GAC GGC
GAA GGC TCA GAT ACC GGA AGA CCA TTT GTG GAG ATG TAT TCC GAA ATA
CCG GAG ATA ATA CAT ATG ACG GAA GGT CGA GAA CTC GTC ATC CCA TGT
CGC GTA ACC TCT CCA AAT ATC ACC GTA ACA CTC AAA AAA TTC CCT CTT
GAC ACG TTG ATA CCG GAC GGC AAA AGA ATA ATA TGG GAT TCA AGG AAA
GGA TTT ATA ATA AGC AAC GCC ACA TAC AAA GAG ATT GGG CTG CTC ACT
TGT GAA GCC ACT GTT AAT GGG CAC TTG TAT AAG ACT AAT TAT CTC ACC
CAC CGC CAG ACG AAT ACT ATA ATA GAT GTC GTT CTG AGC CCA AGT CAT
GGG ATT GAA CTT TCT GTT GGC GAA AAG CTC GTG TTG AAT TGC ACT GCT
AGG ACG GAG CTG AAT GTT GGT ATA GAT TTC AAT TGG GAA TAT CCT AGC
TCT AAA CAC CAG CAC AAA AAA CTC GTT AAT CGC GAC TTG AAG ACG CAG
TCA GGA TCA GAG ATG AAA AAG TTC CTC TCA ACG CTG ACT ATA GAT GGA
GTA ACG AGA TCC GAC CAG GGA TTG TAC ACC TGC GCC GCG TCT TCC GGG
CTC ATG ACA AAA AAA AAC AGC ACT TTC GTA CGC GTC CAT GAA AAA TAG

(SEQ ID NO: 17) [00206] MPLLLLLPLLWAGALAQ VQLQE S GP GLVRP S Q TL SLTC TV S GY S IT SDHA
WSWVRQPPGRGLEWIGYISYSGITTYNPSLKSRVTMLRDTSKNQFSLRLSSVTAADT
AVYYCARSLARTTAMDYWGQGSLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCL
VKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVN
HKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTC
VVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLN
GKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGF
YPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVM
HEALHNHYTQKSLSLSPGGEGSGDGGEGSGDGEGSDTGRPFVEMYSEIPEIIHMTEGR
ELVIPCRVTSPNITVTLKKFPLDTLIPDGKRIIWDSRKGFIISNATYKEIGLLTCEATVNG
HLYKTNYLTHRQTNTIIDVVLSPSHGIELSVGEKLVLNCTARTELNVGIDFNWEYPSS
KHQHKKLVNRDLKTQ S GSEMKKFL S TLTID GVTRSD Q GLYT CAA S SGLMTKKNSTF
VRVHEK
(SEQ ID NO: 18) [00207] ATG CCC TTG CTG CTG TTG CTG CCC CTT CTC TGG GCA GGG GCG
CTG GCT GAC ATT CAA ATG ACT CAG TCT CCA TCC AGT CTC TCC GCT TCT
GTG GGG GAC CGA GTA ACC ATA ACA TGT CGG GCA TCT CAG GAC ATA AGC
TCA TAC TTG AAT TGG TAT CAG CAG AAA CCA GGG AAG GCG CCC AAG CTT
CTT ATC TAC TAT ACA TCA AGA CTT CAT AGC GGG GTG CCA AGC CGA TTC
AGT GGC AGC GGT TCA GGA ACA GAC TTT ACG TTC ACC ATT TCA TCT TTG
CAG CCA GAA GAT ATA GCT ACG TAC TAC TGT CAG CAA GGA AAT ACG TTG
CCG TAC ACC TTT GGC CAG GGC ACA AAA GTC GAA ATT AAG CGA ACC GTA
GCA GCC CCG AGT GTC TTT ATC TTT CCT CCC TCA GAT GAG CAA CTT AAA
AGC GGG ACA GCC TCA GTA GTT TGC CTC CTG AAC AAT TTC TAC CCA CGG
GAA GCC AAG GTG CAG TGG AAG GTG GAC AAT GCT CTT CAG TCC GGC AAC
TCT CAG GAA AGT GTT ACC GAG CAA GAC TCT AAA GAC TCA ACT TAC AGC
CTC AGC TCC ACC CTC ACT TTG TCC AAG GCT GAT TAC GAA AAA CAT AAG
GTA TAT GCC TGC GAA GTT ACG CAC CAA GGA CTT TCA TCC CCG GTG ACA
AAG AGC TTC AAC AGA GGC GAA TGT GGA GAG GGG TCC GGC GAC GGC GGT
GAA GGG TCT GGT GAT GGG GAA GGT TCC GAT ACC GGT CGA CCC TTC GTC
GAG ATG TAT TCT GAG ATT CCG GAA ATC ATC CAC ATG ACC GAA GGA CGA

GAG CTT GTA ATT CCT TGC CGA GTT ACA TCA CCC AAC ATA ACG GTG ACA
CTC AAG AAG TTT CCT TTG GAT ACA TTG ATT CCG GAC GGG AAG CGC ATA
ATT TGG GAT AGT AGA AAG GGT TTT ATT ATC AGC AAC GCT ACG TAT AAG
GAG ATA GGT CTG CTC ACT TGT GAA GCC ACT GTG AAT GGG CAC CTG TAC
AAA ACA AAT TAT CTC ACC CAC CGA CAG ACT AAC ACC ATT ATC GAT GTT
GTT TTG TCT CCA TCT CAT GGA ATC GAA CTT AGT GTC GGA GAA AAG CTC
GTA CTG AAT TGC ACA GCC CGA ACG GAA CTT AAT GTT GGG ATT GAC TTT
AAT TGG GAG TAT CCG TCT TCT AAG CAT CAA CAC AAG AAG CTT GTT AAC
AGG GAT CTC AAG ACG CAA TCC GGA TCA GAA ATG AAA AAA TTT CTC TCC
ACT CTT ACT ATA GAT GGA GTC ACA CGC TCC GAC CAA GGT CTC TAC ACG
TGC GCA GCT AGT AGT GGT CTG ATG ACC AAA AAG AAC TCT ACG TTC GTG
AGA GTA CAT GAG AAG TAG
(SEQ ID NO: 19) [00208] MPLLLLLPLLWAGALADIQMTQSPSSLSASVGDRVTITCRASQDISSYLN
WYQQKPGKAPKLLIYYTSRLHSGVPSRFSGSGSGTDFTFTISSLQPEDIATYYCQQGN
TLPYTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWK
VDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVT
KSFNRGECGEGSGDGGEGSGDGEGSDTGRPFVEMYSEIPEIIHMTEGRELVIPCRVTSP
NITVTLKKFPLDTLIPDGKRIIWDSRKGFIISNATYKEIGLLTCEATVNGHLYKTNYLT
HRQTNTIIDVVLSPSHGIELSVGEKLVLNCTARTELNVGIDFNWEYPSSKHQHKKLVN
RDLKTQSGSEMKKFLSTLTIDGVTRSDQGLYTCAASSGLMTKKNSTFVRVHEK
(SEQ. ID. NO. 20) [00209] ATG CCC CTG CTT CTC CTC TTG CCG TTG CTC TGG GCT GGT GCT
TTG GCG CAA GTA CAA CTT CAA GAA TCA GGT CCC GGG CTC GTG CGG CCT
TCA CAA ACA CTT AGC CTC ACC TGC ACT GTG TCC GGG TAT AGC ATA ACA
AGT GAC CAC GCG TGG AGC TGG GTG CGG CAG CCT CCT GGT CGC GGC CTC
GAG TGG ATT GGA TAC ATA TCC TAC TCA GGA ATC ACT ACA TAT AAT CCA
AGT TTG AAA TCC CGA GTT ACC ATG TTG AGG GAC ACG AGT AAA AAT CAG
TTC AGT CTG AGG TTG TCA AGC GTA ACG GCG GCT GAT ACG GCT GTT TAT
TAC TGT GCA AGA AGT TTG GCA CGA ACA ACC GCG ATG GAC TAC TGG GGT
CAA GGC TCA TTG GTA ACT GTG AGC TCT GCG TCT ACC AAG GGC CCT AGC
GTT TTT CCT CTG GCC CCT TCC TCC AAG TCC ACG TCC GGT GGA ACA GCT

GCT CTC GGC TGT TTG GTA AAA GAT TAT TTC CCA GAA CCC GTT ACT GTG
TCA TGG AAC TCT GGT GCT TTG ACA AGT GGA GTC CAT ACT TTT CCT GCC
GTT CTG CAA TCA AGT GGG CTC TAT AGC TTG TCC TCA GTT GTC ACA GTA
CCA TCA TCA AGC CTG GGT ACA CAG ACT TAT ATA TGC AAT GTG AAC CAC
AAG CCT TCC AAT ACG AAA GTC GAC AAG AAG GTC GAG CCC AAG TCA TGC
GAC AAG ACC CAT ACC TGC CCC CCA TGT CCA GCC CCC GAA CTG CTG GGC
GGA CCC TCA GTC TTC CTC TTT CCA CCA AAG CCG AAA GAT ACC CTT ATG
ATC TCT AGG ACC CCC GAG GTA ACG TGC GTT GTC GTC GAT GTG TCT CAC
GAG GAC CCG GAG GTC AAG TTC AAT TGG TAC GTC GAT GGC GTC GAG GTT
CAT AAC GCG AAG ACT AAA CCG AGG GAG GAA CAA TAC AAC TCT ACG TAC
CGA GTA GTG TCC GTG TTG ACA GTA CTG CAT CAA GAT TGG CTC AAT GGT
AAA GAA TAT AAA TGC AAG GTC TCT AAC AAA GCG TTG CCT GCG CCA ATC
GAA AAA ACT ATT AGC AAA GCT AAG GGT CAA CCG CGA GAG CCT CAG GTA
TAC ACG CTT CCT CCG TCC CGA GAA GAG ATG ACG AAA AAT CAA GTC TCC
CTG ACA TGT CTT GTT AAG GGT TTT TAC CCT TCT GAC ATT GCT GTC GAA
TGG GAG TCC AAT GGC CAG CCC GAG AAC AAC TAT AAG ACG ACG CCT CCC
GTC TTG GAT AGT GAC GGA AGC TTT TTC CTG TAT TCT AAA TTG ACC GTG
GAC AAG AGC CGG TGG CAA CAG GGT AAC GTC TTT TCA TGC TCC GTA ATG
CAC GAG GCG CTT CAT AAC CAC TAC ACC CAA AAG AGT CTC TCA TTG TCT
CCC GGT GGC GGT TCA GGT GGG GGG GGA AGC GGT GGT GGA TCT GAC ACT
GGA CGG CCT TTC GTT GAG ATG TAC TCA GAA ATT CCG GAG ATC ATT CAC
ATG ACA GAA GGG AGG GAG TTG GTG ATA CCT TGC CGG GTT ACA TCA CCA
AAC ATA ACT GTA ACA CTC AAA AAA TTC CCC CTG GAT ACA CTT ATC CCT
GAT GGA AAG CGA ATA ATA TGG GAC AGT AGA AAA GGA TTT ATC ATT AGC
AAC GCA ACG TAT AAA GAA ATC GGA TTG CTT ACC TGC GAA GCG ACG GTG
AAT GGC CAT CTG TAC AAA ACG AAC TAC CTC ACG CAC CGA CAA ACG AAC
ACT ATC ATA GAT GTA GTT TTG AGT CCT AGT CAC GGT ATT GAG CTC AGC
GTC GGG GAG AAA CTG GTC CTT AAC TGT ACT GCT AGA ACG GAA CTC AAC
GTG GGT ATA GAT TTC AAC TGG GAG TAC CCG TCA TCC AAA CAT CAA CAC
AAG AAA CTT GTC AAC CGA GAC CTG AAG ACA CAA TCT GGA TCA GAG ATG
AAG AAG TTT TTG TCT ACT CTT ACA ATT GAT GGG GTC ACT CGG TCT GAT
CAA GGA CTG TAT ACC TGC GCA GCC AGT TCA GGG TTG ATG ACT AAA AAA
AAT TCC ACC TTC GTA CGA GTC CAC GAG AAG TAG
(SEQ ID NO: 21) [00210] MPLLLLLPLLWAGALAQVQLQESGPGLVRPSQTLSLTCTVSGYSITSDHA
WSWVRQPPGRGLEWIGYISYSGITTYNPSLKSRVTMLRDTSKNQFSLRLSSVTAADT
AVYYCARSLARTTAMDYWGQGSLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCL
VKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVN
HKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTC
VVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLN
GKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGF
YPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVM
HEALHNHYTQKSLSLSPGGGSGGGGSGGGSDTGRPFVEMYSEIPEIIHMTEGRELVIP
CRVTSPNITVTLKKFPLDTLIPDGKRIIWDSRKGFIISNATYKEIGLLTCEATVNGHLYK
TNYLTHRQTNTIIDVVLSPSHGIELSVGEKLVLNCTARTELNVGIDFNWEYPSSKHQH
KKLVNRDLKTQSGSEMKKFLSTLTIDGVTRSDQGLYTCAASSGLMTKKNSTFVRVH
EK
(SEQ ID NO: 22) [00211] ATG CCT CTG CTC CTT CTC CTG CCA TTG TTG TGG GCT GGT GCG
CTC GCA GAT ATT CAA ATG ACT CAG TCT CCT TCA AGC CTT TCC GCC TCA
GTC GGC GAC AGA GTA ACA ATA ACT TGT CGG GCG TCT CAA GAT ATC TCC
TCA TAT TTG AAT TGG TAC CAG CAA AAA CCC GGT AAA GCA CCA AAG CTT
CTC ATC TAC TAT ACC TCA AGA CTG CAT TCC GGG GTG CCG AGC CGG TTT
AGC GGA TCT GGA TCT GGA ACA GAC TTT ACA TTC ACG ATT TCC AGC CTG
CAG CCG GAG GAT ATT GCC ACC TAT TAT TGT CAG CAG GGA AAC ACG TTG
CCT TAC ACT TTC GGA CAG GGA ACC AAA GTG GAG ATA AAG AGG ACT GTT
GCC GCA CCG AGC GTG TTT ATC TTT CCT CCT TCA GAT GAG CAG CTT AAG
TCT GGT ACA GCC TCA GTT GTA TGT TTG CTG AAC AAC TTC TAC CCA AGG
GAA GCT AAA GTA CAG TGG AAG GTT GAT AAT GCC CTT CAA TCC GGG AAC
TCT CAA GAG TCT GTA ACA GAA CAA GAT AGT AAG GAC TCA ACG TAT AGC
CTT TCC AGC ACG TTG ACG CTG AGT AAG GCA GAC TAT GAA AAG CAC AAG
GTC TAC GCG TGC GAG GTG ACA CAC CAA GGC CTG TCT TCC CCT GTA ACC
AAA AGC TTT AAC AGG GGT GAG TGC GGT GGA AGC GGC GGC GGC GGT TCT
GGA GGC GGG TCA GAC ACT GGT CGA CCG TTT GTC GAG ATG TAT TCT GAG
ATA CCT GAG ATT ATC CAC ATG ACA GAA GGA CGG GAA CTG GTG ATC CCT
TGC CGG GTA ACC TCA CCC AAT ATC ACC GTG ACA TTG AAA AAG TTT CCC
CTT GAC ACA CTT ATA CCT GAC GGA AAG AGG ATC ATT TGG GAC AGT CGC

AAG GGT TTC ATC ATT TCC AAC GCA ACA TAT AAA GAG ATA GGA CTT TTG
ACG TGC GAA GCG ACG GTC AAT GGT CAC TTG TAC AAG ACG AAC TAT TTG
ACC CAT AGA CAA ACG AAC ACT ATA ATA GAT GTT GTG CTT AGT CCA AGT
CAC GGG ATA GAA TTG AGT GTA GGC GAG AAG CTT GTA CTC AAT TGT ACG
GCC CGA ACC GAG CTC AAC GTT GGA ATA GAC TTC AAC TGG GAG TAC CCT
AGC AGC AAG CAC CAA CAT AAG AAG CTT GTA AAC CGC GAT TTG AAG ACG
CAG TCA GGC AGT GAA ATG AAA AAG TTC TTG TCC ACT TTG ACG ATT GAT
GGT GTT ACG AGA TCA GAC CAG GGC TTG TAT ACC TGC GCA GCG TCA AGC
GGG CTG ATG ACG AAG AAG AAC TCA ACT TTT GTC AGA GTT CAC GAA AAG
TAG
(SEQ ID NO: 23) [00212] MPLLLLLPLLWAGALADIQMTQSPSSLSASVGDRVTITCRASQDISSYLN
WYQQKPGKAPKLLIYYTSRLHSGVPSRFSGSGSGTDFTFTISSLQPEDIATYYCQQGN
TLPYTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWK
VDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVT
KSFNRGECGGSGGGGSGGGSDTGRPFVEMYSEIPEIIHMTEGRELVIPCRVTSPNITVT
LKKFPLDTLIPDGKRIIWDSRKGFIISNATYKEIGLLTCEATVNGHLYKTNYLTHRQTN
TIIDVVLSPSHGIELSVGEKLVLNCTARTELNVGIDFNWEYPSSKHQHKKLVNRDLKT
QSGSEMKKFLSTLTIDGVTRSDQGLYTCAASSGLMTKKNSTFVRVHEK
(SEQ ID NO: 24) [00213] ATG CCG CTT CTT TTG TTG CTC CCC CTG CTG TGG GCG GGG GCC
CTC GCG CAA GTT CAA CTG CAG GAG AGC GGC CCG GGT TTG GTA CGA CCA
AGC CAA ACA CTC TCA CTT ACA TGC ACC GTG TCA GGG TAT AGC ATT ACC
TCA GAC CAC GCG TGG AGC TGG GTA CGG CAG CCG CCG GGT CGA GGC CTC
GAG TGG ATA GGG TAT ATC TCT TAC TCA GGT ATT ACA ACA TAC AAC CCG
TCT CTT AAG TCT CGC GTG ACC ATG CTG CGG GAT ACA AGC AAA AAC CAG
TTC TCC CTC AGA CTG AGC TCT GTC ACT GCG GCC GAT ACT GCT GTC TAC
TAT TGT GCT CGA AGT TTG GCG AGG ACA ACG GCT ATG GAC TAT TGG GGC
CAA GGA TCC CTG GTA ACA GTT TCT TCT GCA AGT ACG AAA GGC CCA AGT
GTG TTT CCA CTG GCT CCC TCC TCT AAG AGC ACT TCT GGG GGA ACG GCA
GCT CTG GGC TGC CTT GTG AAG GAC TAC TTT CCT GAG CCA GTA ACA GTC
TCC TGG AAT TCA GGA GCC CTT ACT AGC GGT GTT CAT ACG TTC CCG GCC

GTT CTG CAG AGT AGC GGG CTT TAC TCT CTG TCA TCT GTT GTG ACG GTT
CCA TCC AGC AGC TTG GGC ACA CAG ACC TAC ATA TGC AAT GTC AAT CAC
AAA CCT TCT AAT ACA AAG GTG GAT AAA AAA GTC GAG CCT AAG AGT TGC
GAT AAG ACC CAT ACC TGT CCT CCA TGT CCC GCA CCA GAA CTT TTG GGC
GGG CCA TCA GTG TTT CTG TTC CCC CCC AAG CCT AAA GAT ACC CTT ATG
ATT AGT AGA ACA CCC GAA GTG ACC TGT GTA GTA GTG GAT GTT AGC CAT
GAG GAC CCT GAA GTT AAA TTC AAT TGG TAT GTC GAT GGG GTT GAA GTT
CAC AAT GCC AAA ACT AAG CCC CGC GAA GAA CAG TAT AAC AGT ACA TAT
AGG GTC GTT TCA GTA CTG ACA GTA TTG CAC CAG GAC TGG TTG AAC GGA
AAG GAG TAT AAG TGC AAA GTC AGC AAC AAA GCC CTG CCT GCA CCT ATC
GAA AAA ACC ATC AGT AAG GCA AAG GGA CAG CCG AGG GAA CCG CAG GTG
TAC ACG CTC CCC CCG TCC AGA GAA GAG ATG ACA AAG AAC CAG GTC AGC
CTG ACA TGT TTG GTC AAG GGA TTC TAT CCG TCA GAC ATT GCC GTC GAG
TGG GAG AGT AAT GGC CAG CCC GAG AAT AAT TAT AAA ACT ACT CCG CCC
GTG CTT GAC TCC GAC GGG TCA TTT TTC CTC TAT AGC AAA CTG ACC GTG
GAT AAG TCA AGA TGG CAA CAA GGT AAC GTC TTT AGT TGT AGT GTT ATG
CAT GAG GCG CTT CAT AAC CAC TAT ACA CAG AAG AGT TTG AGT TTG TCA
CCT GGT GGG GGG AGC GGT GGT GGA GGT TCT GGT GGT GGT TAT AGC ATG
ACT CCA CCC ACC CTG AAC ATC ACT GAA GAA TCA CAT GTC ATC GAC ACT
GGT GAC TCC TTG TCC ATA AGT TGC CGG GGG CAA CAC CCT CTG GAA TGG
GCC TGG CCC GGT GCA CAG GAG GCC CCA GCG ACT GGC GAC AAG GAC TCA
GAG GAC ACG GGG GTT GTC AGA GAT TGT GAG GGG ACT GAC GCG AGG CCG
TAT TGC AAA GTT CTG CTG CTT CAT GAA GTG CAC GCA AAC GAT ACG GGA
TCT TAC GTG TGC TAC TAC AAA TAT ATA AAG GCC CGG ATT GAA GGT ACG
ACA GCG GCT TCA AGC TAC GTA TTC GTT AGG GAT TTC GAG CAA CCA TTC
ATC AAC AAG CCT GAT ACA TTG TTG GTT AAC CGA AAA GAC GCC ATG TGG
GTC CCT TGC CTC GTC TCC ATT CCG GGA CTT AAT GTA ACA CTC AGG AGC
CAA AGT TCC GTC TTG TGG CCC GAC GGC CAA GAA GTA GTT TGG GAC GAC
AGG CGA GGC ATG CTC GTG AGT ACG CCG CTG CTT CAT GAT GCG CTG TAC
CTT CAA TGC GAG ACG ACT TGG GGT GAC CAA GAC TTT CTC TCT AAC CCT
TTT CTG GTC CAT ATC ACA GGG AAC GAG CTC TAG
(SEQ ID NO: 25) [00214] MPLLLLLPLLWAGALAQVQLQESGPGLVRPSQTLSLTCTVSGYSITSDHA
WSWVRQPPGRGLEWIGYISYSGITTYNPSLKSRVTMLRDTSKNQF SLRLSSVTAADT
AVYYCARSLARTTAMDYWGQGSLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCL
VKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVN
HKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTC
VVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLN
GKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGF
YPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVM
HEALHNHYTQKSLSLSPGGGSGGGGSGGGYSMTPPTLNITEESHVIDTGDSLSISCRG
QHPLEWAWPGAQEAPATGDKDSEDTGVVRDCEGTDARPYCKVLLLHEVHANDTGS
YVCYYKYIKARIEGTTAASSYVFVRDFEQPFINKPDTLLVNRKDAMWVPCLVSIPGL
NVTLRSQSSVLWPDGQEVVWDDRRGMLVSTPLLHDALYLQCETTWGDQDFLSNPF
LVHITGNEL
(SEQ ID NO: 26) [00215] ATG CCC TTG CTC CTG TTG CTC CCC CTG CTC TGG GCA GGA GCT
CTT GCT GAC ATA CAA ATG ACT CAA TCT CCT AGC TCA CTC TCC GCT AGT
GTG GGC GAT CGG GTA cc ATC ACA TGT CGG GCC AGC CAG GAC ATA TCT
TCA TAT CTG AAT TGG TAT CAG CAG AAG CCA GGG AAG GCC CCT AAG CTG
CTT ATC TAC TAC ACG TCA AGG TTG CM TCA GGT GTC CCG TCT CGG TTC
TCT GGT AGT GGG TCC GGG ACT GAC TTT ACA TTC ACA ATT AGT AGC CTC
CAG CCC GAG GAC ATA GCG ACT TAC TAC TGC CAA CAG GGT AAT ACC TTG
CCC TAC ACT TTC GGA CAA GGG cc AAG GTT GAG ATT AAG CGA ACG GTC
GCT GCT CCC AGT GTG TTC ATT TTT CCT CCG TCT GAT GAA CAG TTG AAA
TCC GGG cc GCT AGC GTT GTG TGT CTC CTG AAT AAC TTT TAC CCA AGG
GAG GCC AAA GTT CAA TGG AAA GTA GAT AAC GCC TTG CAG AGT GGA AAC
AGC CAG GAG AGT GTT ACT GAG CAA GAC TCA AAA GAT TCA MC TAT AGC
CTC AGC TCC ACT CTC ACG CTG AGC AAA GCT GAC TAC GAA AAG CAC AAG
GTA TAT GCC TGC GAA GTT ACT CAT CAA GGA CTG AGC TCT CCA GTG ACG
AAG AGT TTC AAC CGG GGG GAA TGC GGC GAA GGC TCC GGA GAC GGC GGT
GAG GGA AGC GGC GAT GGA GAG GGG TCC GAT ACT GGC CGC CCC TTT GTG
GAG ATG TAT TCT GAG ATC CCG GAG ATT ATA CAC ATG ACT GAG GGA CGA
GAG CTC GTT ATC CCA TGT CGA GTA ACG AGT CCG AAT ATA ACG GTC ACG
CTC AAA AAA TTT CCC TTG GAT ACC TTG ATA CCA GAT GGT AAG CGA ATA

ATC TGG GAT TCT CGG AAA GGG TTT ATT ATC TCA AAC GCT ACG TAC AAA
GAA ATA GGG CTT TTG ACT TGT GAG GCT ACA GTT AAT GGA CAT CTT TAT
AAA ACG AAT TAT CTT ACG CAC CGA CAG ACA AAC ACC ATA ATA GAT GTT
GTC CTT TCT CCC TCT CAT GGA ATT GAG TTG AGC GTG GGT GAA AAG TTG
GTG CTG AAC TGC ACC GCT CGC ACT GAG CTT AAT GTC GGA ATT GAT TTT
AAT TGG GAG TAC CCT TCA AGC AAA CAT CAG CAT AAG AAA CTG GTA AAT
AGA GAT CTT AAA ACA CAG TCA GGT AGC GAA ATG AAA AAG TTC CTG AGT
ACG TTG ACA ATC GAC GGT GTG ACT AGA TCC GAT CAA GGT CTC TAT ACA
TGT GCC GCC AGT TCT GGT CTG ATG ACC AAA AAG AAT AGT ACA TTT GTT
CGA GTT CAC GAG AAA TAG
(SEQ ID NO: 27) [00216] MPLLLLLPLLWAGALADIQMTQSPSSLSASVGDRVTITCRASQDISSYLN
WYQQKPGKAPKLLIYYTSRLHSGVPSRFSGSGSGTDFTFTISSLQPEDIATYYCQQGN
TLPYTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWK
VDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVT
KSFNRGECGEGSGDGGEGSGDGEGSDTGRPFVEMYSEIPEIIHMTEGRELVIPCRVTSP
NITVTLKKFPLDTLIPDGKRIIWDSRKGFIISNATYKEIGLLTCEATVNGHLYKTNYLT
HRQTNTIIDVVLSPSHGIELSVGEKLVLNCTARTELNVGIDFNWEYPSSKHQHKKLVN
RDLKTQSGSEMKKFLSTLTIDGVTRSDQGLYTCAASSGLMTKKNSTFVRVHEK
(SEQ ID NO: 28) [00217] ATG CCC CTC CTC CTT TTG CTT CCT CTG CTG TGG GCG GGC GCG
CTG GCA CAA GTA CAA TTG CAA GAG AGC GGC CCA GGT CTC GTA AGG CCG
TCC CAG ACT TTG TCT CTG ACA TGC ACA GTA TCA GGG TAT TCC ATC ACT
AGT GAT CAC GCT TGG TCC TGG GTC CGA CAG CCG CCT GGG AGA GGC CTG
GAG TGG ATA GGG TAC ATC TCC TAC TCC GGA ATA ACG ACG TAC AAC CCG
AGT CTG AAG TCT CGA GTA ACC ATG CTG AGG GAT ACA AGC AAG AAT CAG
TTT TCA TTG AGG CTC TCA TCC GTT ACA GCC GCC GAC ACA GCT GTC TAT
TAT TGC GCT CGC AGT TTG GCC AGA ACC ACT GCA ATG GAT TAC TGG GGC
CAA GGA TCC CTG GTT ACC GTC AGC TCA GCT AGC ACG AAA GGT CCA TCT
GTT TTC CCA CTT GCA CCG TCC AGT AAG TCC ACC TCA GGC GGA ACC GCT
GCC CTT GGA TGC CTG GTC AAG GAT TAT TTC CCC GAG CCA GTC ACA GTC
AGC TGG AAC TCT GGA GCC CTC ACC AGC GGA GTT CAC ACG TTT CCC GCT

GTC TTG CAA AGT TCC GGG CTC TAC AGT CTG AGC TCT GTA GTA ACC GTG
CCC AGT TCA AGC CTT GGG ACC CAA ACT TAC ATA TGT AAT GTA AAT CAC
AAG CCA AGC AAC ACT AAG GTG GAT AAA AAA GTC GAG CCG AAA TCC TGC
GAC AAA ACA CAC ACG TGT CCT CCG TGT CCG GCT CCC GAA TTG CTT GGC
GGC CCC TCC GTG TTT CTG TTC CCA CCG AAG CCA AAG GAC ACT CTG ATG
ATC TCT CGC ACG CCA GAA GTG ACA TGC GTC GTT GTA GAC GTA TCA CAC
GAA GAC CCC GAA GTT AAG TTT AAC TGG TAT GTG GAT GGA GTC GAA GTA
CAT AAT GCC AAG ACG AAA CCA AGG GAA GAA CAA TAC AAT TCT ACA TAT
CGG GTC GTG AGT GTT CTG ACG GTA TTG CAT CAA GAT TGG CTC AAC GGT
AAA GAA TAC AAA TGT AAG GTG AGT AAT AAA GCG CTT CCC GCT CCA ATA
GAG AAG ACA ATA TCC AAA GCT AAA GGT CAG CCA CGG GAG CCG CAA GTT
TAT ACC TTG CCG CCT TCA AGA GAA GAG ATG ACA AAA AAC CAG GTT TCC
CTT ACG TGC CTG GTG AAG GGA TTT TAC CCA AGT GAT ATA GCA GTT GAA
TGG GAG AGC AAC GGT CAA CCA GAA AAC AAC TAC AAG ACT ACT CCC CCA
GTT CTC GAC TCT GAT GGG TCT TTC TTT TTG TAC TCA AAA CTC ACC GTT
GAC AAA TCA AGA TGG CAG CAA GGC AAC GTT TTT TCA TGT AGC GTC ATG
CAT GAG GCC TTG CAC AAC CAC TAC ACG CAA AAA AGC CTC AGT TTG AGT
CCC GGG GGT GGT AGT GGC GGT GGC GGT TCC GGC GGT GGG TAT TCT ATG
ACA CCA CCC ACG CTC AAT ATT ACA GAG GAG AGC CAC GTA ATT GAT ACA
GGT GAT TCT CTG TCC ATT AGT TGC AGG GGT CAA CAT CCG CTG GAA TGG
GCC TGG CCG GGT GCG CAA GAA GCA CCC GCA ACA GGA GAT AAA GAC TCC
GAA GAT ACG GGG GTG GTC AGA GAT TGT GAA GGG ACA GAT GCA AGG CCT
TAT TGT AAG GTT TTG CTT CTC CAC GAG GTA CAT GCG AAC GAT ACT GGG
TCT TAC GTG TGT TAC TAC AAG TAT ATC AAA GCT AGG ATC GAG GGG ACT
ACC GCC GCG AGT TCT TAT GTT TTT GTC CGA GAC TTC GAG CAG CCG TTC
ATC AAT AAA CCT GAC ACA CTG TTG GTA AAC CGG AAA GAC GCC ATG TGG
GTG CCT TGT CTT GTT TCT ATC CCG GGT CTG AAC GTC ACT CTT AGG AGT
CAG TCC AGC GTC CTC TGG CCC GAT GGC CAG GAG GTC GTC TGG GAT GAC
AGA AGG GGC ATG TTG GTA TCC ACT CCG CTT TTG CAC GAT GCG CTG TAC
CTT CAG TGT GAG ACC ACT TGG GGT GAC CAA GAT TTT CTC TCA AAT CCC
TTT CTG GTC CAC ATA ACC GGC AAC GAG CTC TAG
(SEQ ID NO: 29) [00218] MPLLLLLPLLWAGALAQVQLQESGPGLVRPSQTLSLTCTVSGYSITSDHA
WSWVRQPPGRGLEWIGYISYSGITTYNPSLKSRVTMLRDTSKNQFSLRLSSVTAADT
AVYYCARSLARTTAMDYWGQGSLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCL
VKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVN
HKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTC
VVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLN
GKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGF
YPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVM
HEALHNHYTQKSLSLSPGGGSGGGGSGGGYSMTPPTLNITEESHVIDTGDSLSISCRG
QHPLEWAWPGAQEAPATGDKDSEDTGVVRDCEGTDARPYCKVLLLHEVHANDTGS
YVCYYKYIKARIEGTTAASSYVFVRDFEQPFINKPDTLLVNRKDAMWVPCLVSIPGL
NVTLRSQSSVLWPDGQEVVWDDRRGMLVSTPLLHDALYLQCETTWGDQDFLSNPF
LVHITGNEL
(SEQ ID NO: 30) [00219] ATG CCG CTC CTG CTT CTT CTC CCA CTC CTC TGG GCC GGA GCG
CTT GCC GAC ATA CAG ATG ACC CAG TCC CCT AGT AGC CTC AGC GCA AGC
GTT GGA GAT CGG GTG ACT ATA ACG TGC CGA GCG TCC CAA GAC ATT TCT
TCT TAT TTG AAT TGG TAT CAA CAA AAA CCA GGG AAA GCC CCG AAA CTG
CTG ATT TAT TAC ACC AGT CGA CTG CAC TCC GGA GTC CCT AGT CGG TTC
AGC GGG TCT GGA TCA GGT ACT GAT TTT ACC TTT ACT ATA AGC TCA CTC
CAG CCA GAG GAC ATT GCG ACC TAT TAT TGC CAG CAG GGA AAC ACA CTT
CCG TAC ACG TTT GGC CAG GGG ACC AAA GTT GAA ATC AAG AGG ACC GTG
GCA GCC CCC TCA GTT TTC ATA TTC CCT CCG TCT GAC GAG CAG TTG AAG
TCA GGG ACT GCA TCC GTG GTG TGT CTG CTG AAT AAT TTC TAC CCA CGC
GAG GCC AAG GTG CAG TGG AAG GTA GAT AAT GCT CTC CAA TCC GGG AAC
AGC CAA GAG TCT GTT ACT GAA CAA GAT TCC AAA GAC TCT ACC TAT AGC
CTC TCA AGC ACC CTT ACA CTT AGT AAG GCG GAT TAC GAA AAA CAC AAA
GTC TAC GCA TGT GAA GTG ACC CAT CAG GGT CTC AGC AGC CCG GTC ACT
AAA AGC TTT AAC AGG GGG GAA TGT GGG GGG AGT GGT GGT GGA GGT AGC
GGC GGT GGC TCC GAC ACC GGA AGG CCT TTC GTA GAG ATG TAT TCA GAA
ATT CCC GAA ATT ATA CAT ATG ACG GAA GGC AGA GAG CTG GTC ATA CCG
TGT AGA GTA ACA TCA CCC AAC ATA ACT GTT ACG CTT AAA AAG TTC CCA
CTT GAC ACA CTT ATA CCC GAC GGC AAG AGA ATA ATC TGG GAC AGC AGA

AAA GGT TTC ATC ATC TCC AAT GCT ACT TAT AAA GAG ATC GGG CTC CTG
ACG TGC GAG GCG ACC GTA AAC GGG CAT TTG TAC AAA ACC AAC TAT CTC
ACT CAT AGA CAA ACA AAC ACT ATT ATT GAT GTG GTG CTC AGC CCC TCT
CAT GGG ATC GAG CTT TCC GTA GGT GAA AAG CTG GTC CTG AAC TGC ACA
GCA CGG ACT GAG TTG AAT GTA GGG ATA GAT TTC AAC TGG GAA TAC CCG
TCT TCA AAA CAT CAG CAC AAA AAG CTT GTG AAT CGC GAC CTC AAG ACA
CAA TCA GGG TCA GAA ATG AAA AAG TTT CTC TCA ACG CTG ACT ATC GAC
GGC GTC ACG CGG TCC GAT CAG GGC CTT TAC ACT TGT GCG GCC TCT TCT
GGG TTG ATG ACG AAG AAA AAC AGT ACG TTT GTA CGC GTA CAT GAG AAG
TAG
(SEQ ID NO: 31) [00220] MPLLLLLPLLWAGALADIQMTQSPSSLSASVGDRVTITCRASQDISSYLN
WYQQKPGKAPKLLIYYTSRLHSGVPSRFSGSGSGTDFTFTISSLQPEDIATYYCQQGN
TLPYTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWK
VDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVT
KSFNRGECGGSGGGGSGGGSDTGRPFVEMYSEIPEIIHMTEGRELVIPCRVTSPNITVT
LKKFPLDTLIPDGKRIIWDSRKGFIISNATYKEIGLLTCEATVNGHLYKTNYLTHRQTN
TIIDVVLSPSHGIELSVGEKLVLNCTARTELNVGIDFNWEYPSSKHQHKKLVNRDLKT
QSGSEMKKFLSTLTIDGVTRSDQGLYTCAASSGLMTKKNSTFVRVHEK
(SEQ ID NO: 32) [00221] CAG GTG CAG CTG CAG GAATCA GGG CCT GGT TTG GTG CGG CCG
AGT CAG ACG CTC AGC TTG ACT TGT ACG GTG TCA GGT TAC TCTATC ACT
AGC GAT CAT GCC TGG AGC TGG GTA CGA CAA CCA CCG GGT CGG GGT CTC
GAA TGG ATA GGT TAC ATA AGC TAC TCA GGA ATC ACG ACA TAC AAT CCC
TCC CTT AAA AGT CGG GTC ACC ATG CTC CGA GAC ACT AGT AAA AAT CAG
TTC TCC CTG CGG TTG TCC AGC GTG ACT GCT GCC GAC ACG GCG GTC TAT
TAT TGC GCA AGA AGT CTG GCG CGG ACA ACG GCA ATG GAC TAC TGG GGA
CAA GGT TCA CTG GTA ACC GTT AGT TCA GCA AGC ACC AAG GGT CCG TCT
GTC TTT CCA CTC GCG CCT TCT AGC AAG TCA ACC TCA GGG GGG ACT GCC
GCG CTT GGA TGT CTG GTC AAA GAT TAT TTT CCT GAG CCG GTA ACA GTT
AGC TGG AAT TCA GGT GCC CTC ACA TCT GGG GTA CAC ACG TTT CCC GCC
GTG CTT CAG AGC TCT GGC CTC TAC AGT CTT TCT AGC GTG GTC ACC GTC

CCA TCT TCA TCA TTG GGT ACA CAA ACT TAC ATT TGT AAC GTT AAT CAC
AAA CCT AGC AAC ACT AAG GTG GAT AAA AAA GTA GAG CCA AAG TCC TGC
GAC AAG ACT CAC ACC TGT CCT CCC TGT CCA GCA CCC GAA CTT TTG GGC
GGT CCT TCT GTT TTC CTG TTT CCT CCT AAA CCC AAA GAT ACA CTC ATG
ATC TCC AGA ACC CCG GAA GTA ACC TGC GTA GTC GTG GAC GTA TCC CAT
GAG GAT CCC GAG GTA AAA TTC AAC TGG TAC GTA GAC GGG GTC GAG GTG
CAC AAT GCC AAG ACT AAA CCT AGG GAA GAG CAA TAC AAT AGT ACG TAC
AGG GTG GTT TCC GTG CTG ACC GTC CTG CAT CAG GAT TGG CTC AAC GGG
AAA GAG TAT AAA TGT AAG GTG TCA AAC AAA GCT TTG CCG GCA CCA ATA
GAG AAA ACC ATT AGT AAG GCG AAA GGA CAA CCC CGA GAG CCA CAA GTG
TAT ACG TTG CCT CCC AGC CGC GAG GAA ATG ACG AAG AAT CAA GTC TCT
CTG ACT TGT CTG GTG AAG GGT TTT TAC CCG TCT GAT ATA GCT GTC GAA
TGG GAG TCT AAC GGC CAG CCA GAG AAT AAT TAC AAA ACC ACT CCT CCG
GTC TTG GAT TCT GAT GGG AGC TTT TTC CTG TAT TCC AAA TTG ACA GTT
GAT AAA AGT CGG TGG CAG CAG GGG AAC GTC TTC TCC TGT AGC GTC ATG
CAT GAA GCA CTG CAT AAT CAT TAT ACC CAA AAA AGT TTG TCC TTG AGC
CCT GGT GGC GAG GGT TCA GGG GAT GGA GGC GAG GGG TCC GGG GAC GGC
GAA GGC TCA GAT ACC GGA AGA CCA TTT GTG GAG ATG TAT TCC GAA ATA
CCG GAG ATA ATA CAT ATG ACG GAA GGT CGA GAA CTC GTC ATC CCA TGT
CGC GTA ACC TCT CCA AAT ATC ACC GTA ACA CTC AAA AAA TTC CCT CTT
GAC ACG TTG ATA CCG GAC GGC AAA AGA ATA ATA TGG GAT TCA AGG AAA
GGA TTT ATA ATA AGC AAC GCC ACA TAC AAA GAG ATT GGG CTG CTC ACT
TGT GAA GCC ACT GTT AAT GGG CAC TTG TAT AAG ACT AAT TAT CTC ACC
CAC CGC CAG ACG AAT ACT ATA ATA GAT GTC GTT CTG AGC CCA AGT CAT
GGG ATT GAA CTT TCT GTT GGC GAA AAG CTC GTG TTG AAT TGC ACT GCT
AGG ACG GAG CTG AAT GTT GGT ATA GAT TTC AAT TGG GAA TAT CCT AGC
TCT AAA CAC CAG CAC AAA AAA CTC GTT AAT CGC GAC TTG AAG ACG CAG
TCA GGA TCA GAG ATG AAA AAG TTC CTC TCA ACG CTG ACT ATA GAT GGA
GTA ACG AGA TCC GAC CAG GGA TTG TAC ACC TGC GCC GCG TCT TCC GGG
CTC ATG ACA AAA AAA AAC AGC ACT TTC GTA CGC GTC CAT GAA AAA TAG
(SEQ ID NO: 33) [00222] QVQLQESGPGLVRPSQTLSLTCTVSGYSITSDHAWSWVRQPPGRGLEWIG
YISYSGITTYNPSLKSRVTMLRDTSKNQFSLRLSSVTAADTAVYYCARSLARTTAMD

YWGQGSLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGA
LTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSC
DKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWY
VDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIE
KTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENN
YKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG
GEGSGDGGEGSGDGEGSDTGRPFVEMYSEIPEIIHMTEGRELVIPCRVTSPNITVTLKK
FPLDTLIPDGKRIIWDSRKGFIISNATYKEIGLLTCEATVNGHLYKTNYLTHRQTNTIID
VVLSPSHGIELSVGEKLVLNCTARTELNVGIDFNWEYPSSKHQHKKLVNRDLKTQSG
SEMKKFLSTLTIDGVTRSDQGLYTCAASSGLMTKKNSTFVRVHEK
(SEQ ID NO: 34) [00223] GAC ATT CAA ATG ACT CAG TCT CCA TCC AGT CTC TCC GCT TCT
GTG GGG GAC CGA GTA ACC ATA ACA TGT CGG GCA TCT CAG GAC ATA AGC
TCA TAC TTG AAT TGG TAT CAG CAG AAA CCA GGG AAG GCG CCC AAG CTT
CTT ATC TAC TAT ACA TCA AGA CTT CAT AGC GGG GTG CCA AGC CGA TTC
AGT GGC AGC GGT TCA GGA ACA GAC TTT ACG TTC ACC ATT TCA TCT TTG
CAG CCA GAA GAT ATA GCT ACG TAC TAC TGT CAG CAA GGA AAT ACG TTG
CCG TAC ACC TTT GGC CAG GGC ACA AAA GTC GAA ATT AAG CGA ACC GTA
GCA GCC CCG AGT GTC TTT ATC TTT CCT CCC TCA GAT GAG CAA CTT AAA
AGC GGG ACA GCC TCA GTA GTT TGC CTC CTG AAC AAT TTC TAC CCA CGG
GAA GCC AAG GTG CAG TGG AAG GTG GAC AAT GCT CTT CAG TCC GGC AAC
TCT CAG GAA AGT GTT ACC GAG CAA GAC TCT AAA GAC TCA ACT TAC AGC
CTC AGC TCC ACC CTC ACT TTG TCC AAG GCT GAT TAC GAA AAA CAT AAG
GTA TAT GCC TGC GAA GTT ACG CAC CAA GGA CTT TCA TCC CCG GTG ACA
AAG AGC TTC AAC AGA GGC GAA TGT GGA GAG GGG TCC GGC GAC GGC GGT
GAA GGG TCT GGT GAT GGG GAA GGT TCC GAT ACC GGT CGA CCC TTC GTC
GAG ATG TAT TCT GAG ATT CCG GAA ATC ATC CAC ATG ACC GAA GGA CGA
GAG CTT GTA ATT CCT TGC CGA GTT ACA TCA CCC AAC ATA ACG GTG ACA
CTC AAG AAG TTT CCT TTG GAT ACA TTG ATT CCG GAC GGG AAG CGC ATA
ATT TGG GAT AGT AGA AAG GGT TTT ATT ATC AGC AAC GCT ACG TAT AAG
GAG ATA GGT CTG CTC ACT TGT GAA GCC ACT GTG AAT GGG CAC CTG TAC
AAA ACA AAT TAT CTC ACC CAC CGA CAG ACT AAC ACC ATT ATC GAT GTT
GTT TTG TCT CCA TCT CAT GGA ATC GAA CTT AGT GTC GGA GAA AAG CTC

GTA CTG AAT TGC ACA GCC CGA ACG GAA CTT AAT GTT GGG ATT GAC TTT
AAT TGG GAG TAT CCG TCT TCT AAG CAT CAA CAC AAG AAG CTT GTT AAC
AGG GAT CTC AAG ACG CAA TCC GGA TCA GAA ATG AAA AAA TTT CTC TCC
ACT CTT ACT ATA GAT GGA GTC ACA CGC TCC GAC CAA GGT CTC TAC ACG
TGC GCA GCT AGT AGT GGT CTG ATG ACC AAA AAG AAC TCT ACG TTC GTG
AGA GTA CAT GAG AAG TAG
(SEQ ID NO: 35) [00224] DIQMTQSPSSLSASVGDRVTITCRASQDISSYLNWYQQKPGKAPKLLIYYT
SRLHSGVPSRFSGSGSGTDFTFTISSLQPEDIATYYCQQGNTLPYTFGQGTKVEIKRTV
AAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQD
SKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECGEGSGDGGEG
SGDGEGSDTGRPFVEMYSEIPEIIHMTEGRELVIPCRVTSPNITVTLKKFPLDTLIPDGK
RIIWDSRKGFIISNATYKEIGLLTCEATVNGHLYKTNYLTHRQTNTIIDVVLSPSHGIEL
SVGEKLVLNCTARTELNVGIDFNWEYPSSKHQHKKLVNRDLKTQSGSEMKKFLSTL
TIDGVTRSDQGLYTCAASSGLMTKKNSTFVRVHEK
(SEQ. ID. NO. 36) [00225] CAA GTA CAA CTT CAA GAA TCA GGT CCC GGG CTC GTG CGG CCT
TCA CAA ACA CTT AGC CTC ACC TGC ACT GTG TCC GGG TAT AGC ATA ACA
AGT GAC CAC GCG TGG AGC TGG GTG CGG CAG CCT CCT GGT CGC GGC CTC
GAG TGG ATT GGA TAC ATA TCC TAC TCA GGA ATC ACT ACA TAT AAT CCA
AGT TTG AAA TCC CGA GTT ACC ATG TTG AGG GAC ACG AGT AAA AAT CAG
TTC AGT CTG AGG TTG TCA AGC GTA ACG GCG GCT GAT ACG GCT GTT TAT
TAC TGT GCA AGA AGT TTG GCA CGA ACA ACC GCG ATG GAC TAC TGG GGT
CAA GGC TCA TTG GTA ACT GTG AGC TCT GCG TCT ACC AAG GGC CCT AGC
GTT TTT CCT CTG GCC CCT TCC TCC AAG TCC ACG TCC GGT GGA ACA GCT
GCT CTC GGC TGT TTG GTA AAA GAT TAT TTC CCA GAA CCC GTT ACT GTG
TCA TGG AAC TCT GGT GCT TTG ACA AGT GGA GTC CAT ACT TTT CCT GCC
GTT CTG CAA TCA AGT GGG CTC TAT AGC TTG TCC TCA GTT GTC ACA GTA
CCA TCA TCA AGC CTG GGT ACA CAG ACT TAT ATA TGC AAT GTG AAC CAC
AAG CCT TCC AAT ACG AAA GTC GAC AAG AAG GTC GAG CCC AAG TCA TGC
GAC AAG ACC CAT ACC TGC CCC CCA TGT CCA GCC CCC GAA CTG CTG GGC
GGA CCC TCA GTC TTC CTC TTT CCA CCA AAG CCG AAA GAT ACC CTT ATG

ATC TCT AGG ACC CCC GAG GTA ACG TGC GTT GTC GTC GAT GTG TCT CAC
GAG GAC CCG GAG GTC AAG TTC AAT TGG TAC GTC GAT GGC GTC GAG GTT
CAT AAC GCG AAG ACT AAA CCG AGG GAG GAA CAA TAC AAC TCT ACG TAC
CGA GTA GTG TCC GTG TTG ACA GTA CTG CAT CAA GAT TGG CTC AAT GGT
AAA GAA TAT AAA TGC AAG GTC TCT AAC AAA GCG TTG CCT GCG CCA ATC
GAA AAA ACT ATT AGC AAA GCT AAG GGT CAA CCG CGA GAG CCT CAG GTA
TAC ACG CTT CCT CCG TCC CGA GAA GAG ATG ACG AAA AAT CAA GTC TCC
CTG ACA TGT CTT GTT AAG GGT TTT TAC CCT TCT GAC ATT GCT GTC GAA
TGG GAG TCC AAT GGC CAG CCC GAG AAC AAC TAT AAG ACG ACG CCT CCC
GTC TTG GAT AGT GAC GGA AGC TTT TTC CTG TAT TCT AAA TTG ACC GTG
GAC AAG AGC CGG TGG CAA CAG GGT AAC GTC TTT TCA TGC TCC GTA ATG
CAC GAG GCG CTT CAT AAC CAC TAC ACC CAA AAG AGT CTC TCA TTG TCT
CCC GGT GGC GGT TCA GGT GGG GGG GGA AGC GGT GGT GGA TCT GAC ACT
GGA CGG CCT TTC GTT GAG ATG TAC TCA GAA ATT CCG GAG ATC ATT CAC
ATG ACA GAA GGG AGG GAG TTG GTG ATA CCT TGC CGG GTT ACA TCA CCA
AAC ATA ACT GTA ACA CTC AAA AAA TTC CCC CTG GAT ACA CTT ATC CCT
GAT GGA AAG CGA ATA ATA TGG GAC AGT AGA AAA GGA TTT ATC ATT AGC
AAC GCA ACG TAT AAA GAA ATC GGA TTG CTT ACC TGC GAA GCG ACG GTG
AAT GGC CAT CTG TAC AAA ACG AAC TAC CTC ACG CAC CGA CAA ACG AAC
ACT ATC ATA GAT GTA GTT TTG AGT CCT AGT CAC GGT ATT GAG CTC AGC
GTC GGG GAG AAA CTG GTC CTT AAC TGT ACT GCT AGA ACG GAA CTC AAC
GTG GGT ATA GAT TTC AAC TGG GAG TAC CCG TCA TCC AAA CAT CAA CAC
AAG AAA CTT GTC AAC CGA GAC CTG AAG ACA CAA TCT GGA TCA GAG ATG
AAG AAG TTT TTG TCT ACT CTT ACA ATT GAT GGG GTC ACT CGG TCT GAT
CAA GGA CTG TAT ACC TGC GCA GCC AGT TCA GGG TTG ATG ACT AAA AAA
AAT TCC ACC TTC GTA CGA GTC CAC GAG AAG TAG
(SEQ ID NO: 37) [00226] QVQLQESGPGLVRPSQTLSLTCTVSGYSITSDHAWSWVRQPPGRGLEWIG
YISYSGITTYNPSLKSRVTMLRDTSKNQFSLRLSSVTAADTAVYYCARSLARTTAMD
YWGQGSLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGA
LTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSC
DKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWY
VDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIE

KTISKAKGQPREPQVYTLPP SREEMTKNQVSLTCLVKGFYP SDIAVEWESNGQPENN
YKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVF SC SVMHEALHNHYTQKSLSLSPG
GGS GGGGS GGGSD TGRPF VEMY SEIPEIIHMTEGRELVIP CRVT SPNITVTLKKFPLDT
LIPDGKRIIWDSRKGFIISNATYKEIGLLTCEATVNGHLYKTNYLTHRQTNTIIDVVLSP
SHGIELSVGEKLVLNCTARTELNVGIDFNWEYP S SKHQHKKLVNRDLKTQSGSEMK
KFL S TLTID GVTRSD Q GLYT CAA S SGLMTKKNSTFVRVHEK
(SEQ ID NO: 38) [00227] GAT ATT CAA ATG ACT CAG TCT CCT TCA AGC CTT TCC GCC TCA
GTC GGC GAC AGA GTA ACA ATA ACT TGT CGG GCG TCT CAA GAT ATC TCC
TCA TAT TTG AAT TGG TAC CAG CAA AAA CCC GGT AAA GCA CCA AAG CTT
CTC ATC TAC TAT ACC TCA AGA CTG CAT TCC GGG GTG CCG AGC CGG TTT
AGC GGA TCT GGA TCT GGA ACA GAC TTT ACA TTC ACG ATT TCC AGC CTG
CAG CCG GAG GAT ATT GCC ACC TAT TAT TGT CAG CAG GGA AAC ACG TTG
CCT TAC ACT TTC GGA CAG GGA ACC AAA GTG GAG ATA AAG AGG ACT GTT
GCC GCA CCG AGC GTG TTT ATC TTT CCT CCT TCA GAT GAG CAG CTT AAG
TCT GGT ACA GCC TCA GTT GTA TGT TTG CTG AAC AAC TTC TAC CCA AGG
GAA GCT AAA GTA CAG TGG AAG GTT GAT AAT GCC CTT CAA TCC GGG AAC
TCT CAA GAG TCT GTA ACA GAA CAA GAT AGT AAG GAC TCA ACG TAT AGC
CTT TCC AGC ACG TTG ACG CTG AGT AAG GCA GAC TAT GAA AAG CAC AAG
GTC TAC GCG TGC GAG GTG ACA CAC CAA GGC CTG TCT TCC CCT GTA ACC
AAA AGC TTT AAC AGG GGT GAG TGC GGT GGA AGC GGC GGC GGC GGT TCT
GGA GGC GGG TCA GAC ACT GGT CGA CCG TTT GTC GAG ATG TAT TCT GAG
ATA CCT GAG ATT ATC CAC ATG ACA GAA GGA CGG GAA CTG GTG ATC CCT
TGC CGG GTA ACC TCA CCC AAT ATC ACC GTG ACA TTG AAA AAG TTT CCC
CTT GAC ACA CTT ATA CCT GAC GGA AAG AGG ATC ATT TGG GAC AGT CGC
AAG GGT TTC ATC ATT TCC AAC GCA ACA TAT AAA GAG ATA GGA CTT TTG
ACG TGC GAA GCG ACG GTC AAT GGT CAC TTG TAC AAG ACG AAC TAT TTG
ACC CAT AGA CAA ACG AAC ACT ATA ATA GAT GTT GTG CTT AGT CCA AGT
CAC GGG ATA GAA TTG AGT GTA GGC GAG AAG CTT GTA CTC AAT TGT ACG
GCC CGA ACC GAG CTC AAC GTT GGA ATA GAC TTC AAC TGG GAG TAC CCT
AGC AGC AAG CAC CAA CAT AAG AAG CTT GTA AAC CGC GAT TTG AAG ACG
CAG TCA GGC AGT GAA ATG AAA AAG TTC TTG TCC ACT TTG ACG ATT GAT
GGT GTT ACG AGA TCA GAC CAG GGC TTG TAT ACC TGC GCA GCG TCA AGC

GGG CTG ATG ACG AAG AAG AAC TCA ACT TTT GTC AGA GTT CAC GAA AAG
TAG
(SEQ ID NO: 39) [00228] DIQMTQSPSSLSASVGDRVTITCRASQDISSYLNWYQQKPGKAPKLLIYYT
SRLHSGVPSRFSGSGSGTDFTFTISSLQPEDIATYYCQQGNTLPYTFGQGTKVEIKRTV
AAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQD
SKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECGGSGGGGSGG
GSDTGRPFVEMYSEIPEIIHMTEGRELVIPCRVTSPNITVTLKKFPLDTLIPDGKRIIWDS
RKGFIISNATYKEIGLLTCEATVNGHLYKTNYLTHRQTNTIIDVVLSPSHGIELSVGEK
LVLNCTARTELNVGIDFNWEYPSSKHQHKKLVNRDLKTQSGSEMKKFLSTLTIDGVT
RSDQGLYTCAASSGLMTKKNSTFVRVHEK
(SEQ ID NO: 40) [00229] CAA GTT CAA CTG CAG GAG AGC GGC CCG GGT TTG GTA CGA CCA
AGC CAA ACA CTC TCA CTT ACA TGC ACC GTG TCA GGG TAT AGC ATT ACC
TCA GAC CAC GCG TGG AGC TGG GTA CGG CAG CCG CCG GGT CGA GGC CTC
GAG TGG ATA GGG TAT ATC TCT TAC TCA GGT ATT ACA ACA TAC AAC CCG
TCT CTT AAG TCT CGC GTG ACC ATG CTG CGG GAT ACA AGC AAA AAC CAG
TTC TCC CTC AGA CTG AGC TCT GTC ACT GCG GCC GAT ACT GCT GTC TAC
TAT TGT GCT CGA AGT TTG GCG AGG ACA ACG GCT ATG GAC TAT TGG GGC
CAA GGA TCC CTG GTA ACA GTT TCT TCT GCA AGT ACG AAA GGC CCA AGT
GTG TTT CCA CTG GCT CCC TCC TCT AAG AGC ACT TCT GGG GGA ACG GCA
GCT CTG GGC TGC CTT GTG AAG GAC TAC TTT CCT GAG CCA GTA ACA GTC
TCC TGG AAT TCA GGA GCC CTT ACT AGC GGT GTT CAT ACG TTC CCG GCC
GTT CTG CAG AGT AGC GGG CTT TAC TCT CTG TCA TCT GTT GTG ACG GTT
CCA TCC AGC AGC TTG GGC ACA CAG ACC TAC ATA TGC AAT GTC AAT CAC
AAA CCT TCT AAT ACA AAG GTG GAT AAA AAA GTC GAG CCT AAG AGT TGC
GAT AAG ACC CAT ACC TGT CCT CCA TGT CCC GCA CCA GAA CTT TTG GGC
GGG CCA TCA GTG TTT CTG TTC CCC CCC AAG CCT AAA GAT ACC CTT ATG
ATT AGT AGA ACA CCC GAA GTG ACC TGT GTA GTA GTG GAT GTT AGC CAT
GAG GAC CCT GAA GTT AAA TTC AAT TGG TAT GTC GAT GGG GTT GAA GTT
CAC AAT GCC AAA ACT AAG CCC CGC GAA GAA CAG TAT AAC AGT ACA TAT
AGG GTC GTT TCA GTA CTG ACA GTA TTG CAC CAG GAC TGG TTG AAC GGA

AAG GAG TAT AAG TGC AAA GTC AGC AAC AAA GCC CTG CCT GCA CCT ATC
GAA AAA ACC ATC AGT AAG GCA AAG GGA CAG CCG AGG GAA CCG CAG GTG
TAC ACG CTC CCC CCG TCC AGA GAA GAG ATG ACA AAG AAC CAG GTC AGC
CTG ACA TGT TTG GTC AAG GGA TTC TAT CCG TCA GAC ATT GCC GTC GAG
TGG GAG AGT AAT GGC CAG CCC GAG AAT AAT TAT AAA ACT ACT CCG CCC
GTG CTT GAC TCC GAC GGG TCA TTT TTC CTC TAT AGC AAA CTG ACC GTG
GAT AAG TCA AGA TGG CAA CAA GGT AAC GTC TTT AGT TGT AGT GTT ATG
CAT GAG GCG CTT CAT AAC CAC TAT ACA CAG AAG AGT TTG AGT TTG TCA
CCT GGT GGG GGG AGC GGT GGT GGA GGT TCT GGT GGT GGT TAT AGC ATG
ACT CCA CCC ACC CTG AAC ATC ACT GAA GAA TCA CAT GTC ATC GAC ACT
GGT GAC TCC TTG TCC ATA AGT TGC CGG GGG CAA CAC CCT CTG GAA TGG
GCC TGG CCC GGT GCA CAG GAG GCC CCA GCG ACT GGC GAC AAG GAC TCA
GAG GAC ACG GGG GTT GTC AGA GAT TGT GAG GGG ACT GAC GCG AGG CCG
TAT TGC AAA GTT CTG CTG CTT CAT GAA GTG CAC GCA AAC GAT ACG GGA
TCT TAC GTG TGC TAC TAC AAA TAT ATA AAG GCC CGG ATT GAA GGT ACG
ACA GCG GCT TCA AGC TAC GTA TTC GTT AGG GAT TTC GAG CAA CCA TTC
ATC AAC AAG CCT GAT ACA TTG TTG GTT AAC CGA AAA GAC GCC ATG TGG
GTC CCT TGC CTC GTC TCC ATT CCG GGA CTT AAT GTA ACA CTC AGG AGC
CAA AGT TCC GTC TTG TGG CCC GAC GGC CAA GAA GTA GTT TGG GAC GAC
AGG CGA GGC ATG CTC GTG AGT ACG CCG CTG CTT CAT GAT GCG CTG TAC
CTT CAA TGC GAG ACG ACT TGG GGT GAC CAA GAC TTT CTC TCT AAC CCT
TTT CTG GTC CAT ATC ACA GGG AAC GAG CTC TAG
(SEQ ID NO: 41) [00230] QVQLQESGPGLVRPSQTLSLTCTVSGYSITSDHAWSWVRQPPGRGLEWIG
YISYSGITTYNPSLKSRVTMLRDTSKNQFSLRLSSVTAADTAVYYCARSLARTTAMD
YWGQGSLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGA
LTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSC
DKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWY
VDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIE
KTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENN
YKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG
GGSGGGGSGGGYSMTPPTLNITEESHVIDTGDSLSISCRGQHPLEWAWPGAQEAPAT
GDKDSEDTGVVRDCEGTDARPYCKVLLLHEVHANDTGSYVCYYKYIKARIEGTTAA

S SYVFVRDFEQPFINKPDTLLVNRKDAMWVPCLVSIPGLNVTLRSQSSVLWPDGQEV
VWDDRRGMLVSTPLLHDALYLQCETTWGDQDFLSNPFLVHITGNEL
(SEQ ID NO: 42) [00231] GAC ATA CAA ATG ACT CAA TCT CCT AGC TCA CTC TCC GCT AGT
GTG GGC GAT CGG GTA ACC ATC ACA TGT CGG GCC AGC CAG GAC ATA TCT
TCA TAT CTG AAT TGG TAT CAG CAG AAG CCA GGG AAG GCC CCT AAG CTG
CTT ATC TAC TAC ACG TCA AGG TTG CAC TCA GGT GTC CCG TCT CGG TTC
TCT GGT AGT GGG TCC GGG ACT GAC TTT ACA TTC ACA ATT AGT AGC CTC
CAG CCC GAG GAC ATA GCG ACT TAC TAC TGC CAA CAG GGT AAT ACC TTG
CCC TAC ACT TTC GGA CAA GGG ACC AAG GTT GAG ATT AAG CGA ACG GTC
GCT GCT CCC AGT GTG TTC ATT TTT CCT CCG TCT GAT GAA CAG TTG AAA
TCC GGG ACC GCT AGC GTT GTG TGT CTC CTG AAT AAC TTT TAC CCA AGG
GAG GCC AAA GTT CAA TGG AAA GTA GAT AAC GCC TTG CAG AGT GGA AAC
AGC CAG GAG AGT GTT ACT GAG CAA GAC TCA AAA GAT TCA ACC TAT AGC
CTC AGC TCC ACT CTC ACG CTG AGC AAA GCT GAC TAC GAA AAG CAC AAG
GTA TAT GCC TGC GAA GTT ACT CAT CAA GGA CTG AGC TCT CCA GTG ACG
AAG AGT TTC AAC CGG GGG GAA TGC GGC GAA GGC TCC GGA GAC GGC GGT
GAG GGA AGC GGC GAT GGA GAG GGG TCC GAT ACT GGC CGC CCC TTT GTG
GAG ATG TAT TCT GAG ATC CCG GAG ATT ATA CAC ATG ACT GAG GGA CGA
GAG CTC GTT ATC CCA TGT CGA GTA ACG AGT CCG AAT ATA ACG GTC ACG
CTC AAA AAA TTT CCC TTG GAT ACC TTG ATA CCA GAT GGT AAG CGA ATA
ATC TGG GAT TCT CGG AAA GGG TTT ATT ATC TCA AAC GCT ACG TAC AAA
GAA ATA GGG CTT TTG ACT TGT GAG GCT ACA GTT AAT GGA CAT CTT TAT
AAA ACG AAT TAT CTT ACG CAC CGA CAG ACA AAC ACC ATA ATA GAT GTT
GTC CTT TCT CCC TCT CAT GGA ATT GAG TTG AGC GTG GGT GAA AAG TTG
GTG CTG AAC TGC ACC GCT CGC ACT GAG CTT AAT GTC GGA ATT GAT TTT
AAT TGG GAG TAC CCT TCA AGC AAA CAT CAG CAT AAG AAA CTG GTA AAT
AGA GAT CTT AAA ACA CAG TCA GGT AGC GAA ATG AAA AAG TTC CTG AGT
ACG TTG ACA ATC GAC GGT GTG ACT AGA TCC GAT CAA GGT CTC TAT ACA
TGT GCC GCC AGT TCT GGT CTG ATG ACC AAA AAG AAT AGT ACA TTT GTT
CGA GTT CAC GAG AAA TAG
(SEQ ID NO: 43) [00232] DIQMTQSPSSLSASVGDRVTITCRASQDISSYLNWYQQKPGKAPKLLIYYT
SRLHSGVPSRFSGSGSGTDFTFTISSLQPEDIATYYCQQGNTLPYTFGQGTKVEIKRTV
AAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQD
SKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECGEGSGDGGEG
SGDGEGSDTGRPFVEMYSEIPEIIHMTEGRELVIPCRVTSPNITVTLKKFPLDTLIPDGK
RIIWDSRKGFIISNATYKEIGLLTCEATVNGHLYKTNYLTHRQTNTIIDVVLSPSHGIEL
SVGEKLVLNCTARTELNVGIDFNWEYPSSKHQHKKLVNRDLKTQSGSEMKKFLSTL
TIDGVTRSDQGLYTCAASSGLMTKKNSTFVRVHEK
(SEQ ID NO: 44) [00233] CAA GTA CAA TTG CAA GAG AGC GGC CCA GGT CTC GTA AGG CCG
TCC CAG ACT TTG TCT CTG ACA TGC ACA GTA TCA GGG TAT TCC ATC ACT
AGT GAT CAC GCT TGG TCC TGG GTC CGA CAG CCG CCT GGG AGA GGC CTG
GAG TGG ATA GGG TAC ATC TCC TAC TCC GGA ATA ACG ACG TAC AAC CCG
AGT CTG AAG TCT CGA GTA ACC ATG CTG AGG GAT ACA AGC AAG AAT CAG
TTT TCA TTG AGG CTC TCA TCC GTT ACA GCC GCC GAC ACA GCT GTC TAT
TAT TGC GCT CGC AGT TTG GCC AGA ACC ACT GCA ATG GAT TAC TGG GGC
CAA GGA TCC CTG GTT ACC GTC AGC TCA GCT AGC ACG AAA GGT CCA TCT
GTT TTC CCA CTT GCA CCG TCC AGT AAG TCC ACC TCA GGC GGA ACC GCT
GCC CTT GGA TGC CTG GTC AAG GAT TAT TTC CCC GAG CCA GTC ACA GTC
AGC TGG AAC TCT GGA GCC CTC ACC AGC GGA GTT CAC ACG TTT CCC GCT
GTC TTG CAA AGT TCC GGG CTC TAC AGT CTG AGC TCT GTA GTA ACC GTG
CCC AGT TCA AGC CTT GGG ACC CAA ACT TAC ATA TGT AAT GTA AAT CAC
AAG CCA AGC AAC ACT AAG GTG GAT AAA AAA GTC GAG CCG AAA TCC TGC
GAC AAA ACA CAC ACG TGT CCT CCG TGT CCG GCT CCC GAA TTG CTT GGC
GGC CCC TCC GTG TTT CTG TTC CCA CCG AAG CCA AAG GAC ACT CTG ATG
ATC TCT CGC ACG CCA GAA GTG ACA TGC GTC GTT GTA GAC GTA TCA CAC
GAA GAC CCC GAA GTT AAG TTT AAC TGG TAT GTG GAT GGA GTC GAA GTA
CAT AAT GCC AAG ACG AAA CCA AGG GAA GAA CAA TAC AAT TCT ACA TAT
CGG GTC GTG AGT GTT CTG ACG GTA TTG CAT CAA GAT TGG CTC AAC GGT
AAA GAA TAC AAA TGT AAG GTG AGT AAT AAA GCG CTT CCC GCT CCA ATA
GAG AAG ACA ATA TCC AAA GCT AAA GGT CAG CCA CGG GAG CCG CAA GTT
TAT ACC TTG CCG CCT TCA AGA GAA GAG ATG ACA AAA AAC CAG GTT TCC
CTT ACG TGC CTG GTG AAG GGA TTT TAC CCA AGT GAT ATA GCA GTT GAA

TGG GAG AGC AAC GGT CAA CCA GAA AAC AAC TAC AAG ACT ACT CCC CCA
GTT CTC GAC TCT GAT GGG TCT TTC TTT TTG TAC TCA AAA CTC ACC GTT
GAC AAA TCA AGA TGG CAG CAA GGC AAC GTT TTT TCA TGT AGC GTC ATG
CAT GAG GCC TTG CAC AAC CAC TAC ACG CAA AAA AGC CTC AGT TTG AGT
CCC GGG GGT GGT AGT GGC GGT GGC GGT TCC GGC GGT GGG TAT TCT ATG
ACA CCA CCC ACG CTC AAT ATT ACA GAG GAG AGC CAC GTA ATT GAT ACA
GGT GAT TCT CTG TCC ATT AGT TGC AGG GGT CAA CAT CCG CTG GAA TGG
GCC TGG CCG GGT GCG CAA GAA GCA CCC GCA ACA GGA GAT AAA GAC TCC
GAA GAT ACG GGG GTG GTC AGA GAT TGT GAA GGG ACA GAT GCA AGG CCT
TAT TGT AAG GTT TTG CTT CTC CAC GAG GTA CAT GCG AAC GAT ACT GGG
TCT TAC GTG TGT TAC TAC AAG TAT ATC AAA GCT AGG ATC GAG GGG ACT
ACC GCC GCG AGT TCT TAT GTT TTT GTC CGA GAC TTC GAG CAG CCG TTC
ATC AAT AAA CCT GAC ACA CTG TTG GTA AAC CGG AAA GAC GCC ATG TGG
GTG CCT TGT CTT GTT TCT ATC CCG GGT CTG AAC GTC ACT CTT AGG AGT
CAG TCC AGC GTC CTC TGG CCC GAT GGC CAG GAG GTC GTC TGG GAT GAC
AGA AGG GGC ATG TTG GTA TCC ACT CCG CTT TTG CAC GAT GCG CTG TAC
CTT CAG TGT GAG ACC ACT TGG GGT GAC CAA GAT TTT CTC TCA AAT CCC
TTT CTG GTC CAC ATA ACC GGC AAC GAG CTC TAG
(SEQ ID NO: 45) [00234] QVQLQESGPGLVRPSQTLSLTCTVSGYSITSDHAWSWVRQPPGRGLEWIG
YISYSGITTYNPSLKSRVTMLRDTSKNQFSLRLSSVTAADTAVYYCARSLARTTAMD
YWGQGSLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGA
LTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSC
DKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWY
VDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIE
KTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENN
YKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG
GGSGGGGSGGGYSMTPPTLNITEESHVIDTGDSLSISCRGQHPLEWAWPGAQEAPAT
GDKDSEDTGVVRDCEGTDARPYCKVLLLHEVHANDTGSYVCYYKYIKARIEGTTAA
SSYVFVRDFEQPFINKPDTLLVNRKDAMWVPCLVSIPGLNVTLRSQSSVLWPDGQEV
VWDDRRGMLVSTPLLHDALYLQCETTWGDQDFLSNPFLVHITGNEL
(SEQ ID NO: 46) [00235] GAC ATA CAG ATG ACC CAG TCC CCT AGT AGC CTC AGC GCA AGC
GTT GGA GAT CGG GTG ACT ATA ACG TGC CGA GCG TCC CAA GAC ATT TCT
TCT TAT TTG AAT TGG TAT CAA CAA AAA CCA GGG AAA GCC CCG AAA CTG
CTG ATT TAT TAC ACC AGT CGA CTG CAC TCC GGA GTC CCT AGT CGG TTC
AGC GGG TCT GGA TCA GGT ACT GAT TTT ACC TTT ACT ATA AGC TCA CTC
CAG CCA GAG GAC ATT GCG ACC TAT TAT TGC CAG CAG GGA AAC ACA CTT
CCG TAC ACG TTT GGC CAG GGG ACC AAA GTT GAA ATC AAG AGG ACC GTG
GCA GCCCC TCA GTT TTC ATA TTC CCT CCG TCT GAC GAG CAG TTG AAG TCA
GGG ACT GCA TCC GTG GTG TGT CTG CTG AAT AAT TTC TAC CCA CGC GAG
GCC AAG GTG CAG TGG AAG GTA GAT AAT GCT CTC CAA TCC GGG AAC AGC
CAA GAG TCT GTT ACT GAA CAA GAT TCC AAA GAC TCT ACC TAT AGC CTC
TCA AGC ACC CTT ACA CTT AGT AAG GCG GAT TAC GAA AAA CAC AAA GTC
TAC GCA TGT GAA GTG ACC CAT CAG GGT CTC AGC AGC CCG GTC ACT AAA
AGC TTT AAC AGG GGG GAA TGT GGG GGG AGT GGT GGT GGA GGT AGC GGC
GGT GGC TCC GAC ACC GGA AGG CCT TTC GTA GAG ATG TAT TCA GAA ATT
CCC GAA ATT ATA CAT ATG ACG GAA GGC AGA GAG CTG GTC ATA CCG TGT
AGA GTA ACA TCA CCC AAC ATA ACT GTT ACG CTT AAA AAG TTC CCA CTT
GAC ACA CTT ATA CCC GAC GGC AAG AGA ATA ATC TGG GAC AGC AGA AAA
GGT TTC ATC ATC TCC AAT GCT ACT TAT AAA GAG ATC GGG CTC CTG ACG
TGC GAG GCG ACC GTA AAC GGG CAT TTG TAC AAA ACC AAC TAT CTC ACT
CAT AGA CAA ACA AAC ACT ATT ATT GAT GTG GTG CTC AGC CCC TCT CAT
GGG ATC GAG CTT TCC GTA GGT GAA AAG CTG GTC CTG AAC TGC ACA GCA
CGG ACT GAG TTG AAT GTA GGG ATA GAT TTC AAC TGG GAA TAC CCG TCT
TCA AAA CAT CAG CAC AAA AAG CTT GTG AAT CGC GAC CTC AAG ACA CAA
TCA GGG TCA GAA ATG AAA AAG TTT CTC TCA ACG CTG ACT ATC GAC GGC
GTC ACG CGG TCC GAT CAG GGC CTT TAC ACT TGT GCG GCC TCT TCT GGG
TTG ATG ACG AAG AAA AAC AGT ACG TTT GTA CGC GTA CAT GAG AAG TAG
(SEQ ID NO: 47) [00236] DIQMTQSPSSLSASVGDRVTITCRASQDISSYLNWYQQKPGKAPKLLIYYT
SRLHSGVPSRFSGSGSGTDFTFTISSLQPEDIATYYCQQGNTLPYTFGQGTKVEIKRTV
AAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQD
SKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECGGSGGGGSGG
GSDTGRPFVEMYSEIPEIIHMTEGRELVIPCRVTSPNITVTLKKFPLDTLIPDGKRIIWDS

RKGF II SNAT YKEIGLLT CEATVNGHLYK TNYLTHRQ TNTIIDVVL SP SHGIELSVGEK
LVLNCTARTELNVGIDFNWEYPS SKHQHKKLVNRDLKTQ S GS EMKKFL S TLTID GVT
RSDQGLYTCAAS SGLMTKKNSTFVRVHEK
(SEQ ID NO: 48) [00237] :EVQLVESGGGLVQPGRSLRLSCAASRFTFDDYAMHWVRQAPGKGLEWV
S GI SWN S GRIGYAD S VKGRITISR DNAENSLFLQMNGLRAEDTALYYC AK GRD S FDI
WGQ GTMVIVS SAS TKGP SVFPLAPS SK ST SGGTAALGCLVKD YFPEPVINSWNSGA
LT S GVHTFP AVLQ S S GLY S LS S VVT VP S S SLGTQTYICNVNHKP SNTKVDKKVEPK SC
DKTFITC PPCP AP ELLG-GPS WITT PKPKIYILM RTPEVTCVVVDV SHEDPEVKFNWY
VDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIE
KTISK AKGQPREPQ VYTL PP SRDELTKNQV SUICINK GFYPSDIAVEWESNG-QPENN
YKTIPPVLDSDGSITLYSKLTVDKSRWQQGNVF SC SVMHEALHNHYTQK S LSL SP G
(SEQ ID NO: 49) [00238] DIQMTQSPSSVSASVGDRVTIITCRASQGISSWLAWYQQKPGK APKLLIYG
AS SLESGVP SRF SGSGSGTDFTLTIS SLQPEDFASYYCQQANSFPYTFGQG-TKLEIKRT
VAAPSVF IFPPSDEQLKSGTASVVC LLNNTYPREAKVQWKVDNALQSGNSQESVTEQ
D SKD S TY SL S STLTLSKADYEKHK VYAC E VTHQGL S SPVTKSFNRGEC
(SEQ ID NO; 50) [00239] QVQLQESGPGLVKP SETLSLTCAVSGHSISHDHAWSWVRQPPGEGLEWI
GEIS Y S GITNYNP SLQ GRVTI SRDNSKNTLYLQMNSLRAED TAVYYC ARS LART TAM
DYWGEGTLVTVS SAS TKGP SVFPLAPS SKSTSGGTAALGCLVKDYFPEPVTVSWNSG
ALT S GVHTFPAVLQ S SGLYSLSSVVTVPS SNFGTQTYTCNVDHKP SNTKVDKTVERK
SCVECPPCPAPPVAGP SVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVD
GVEVHNAKTKPREEQFNSTFRVVSVLTVVHQDWLNGKEYKCKVSNKGLPAPIEKTIS
KTKGQPREPQVYTLPP SQEEMTKNQVSLTCLVKGFYP SDIAVEWESNGQPENNYKTT
PPMLDSDGSFFLYSKLTVDKSRWQEGNVF SC SVMHEALHAHYTQK SL SL SP
(SEQ ID NO: 51) [00240] DIQMTQ SP S SLSASVGDSVTITCQASTDIS SHLNWYQQKPGKAPELLIYYG
SHLLSGVP SRF S GS GS GTDF TF TIS SLEAEDAAT YYC GQ GNRLP YTF GQ GTKVEIERTV

AAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQD
SKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
(SEQ ID NO: 52) [00241] SDHAWS (SEQ ID NO: 53) [00242] YISYSGITTYNPSLKS (SEQ ID NO: 54) [00243] SLARTTAMDY (SEQ ID NO: 55) [00244] RASQDISSYLN (SEQ ID NO: 56) [00245] YTSRLHS (SEQ ID NO: 57) [00246] QQGNTLPYT (SEQ ID NO: 58) [00247] ATG CCG CTC TTG CTC CTT CTT CCA TTG CTC TGG GCG GGC GCA
CTG GCC GAT ATC CAA ATG ACG CAA AGT CCA AGT TCT CTT TCA GCC AGC
GTC GGA GAT AGA GTC ACT ATA ACA TGC CGC GCG AGC CAG GAT ATA TCA
AGC TAC CTT AAT TGG TAT CAA CAA AAA CCG GGT AAA GCG CCG AAA CTC
TTG ATT TAT TAT ACC AGT AGG CTC CAC TCC GGT GTA CCA AGT CGG TTC
AGT GGC TCC GGG AGT GGA ACC GAC TTC ACA
TTT ACA ATA AGC TCT TTG CAA CCA GAG GAT ATT GCA ACT TAC TAT TGC
CAG CAA GGC AAC ACG TTG CCT TAC ACG TTT GGA CAG GGA ACA AAG GTT
GAG ATA AAG CGA GGG GGC GGT GGC AGT GGT GGA GGG GGT AGC GGA GGC
GGG GGG AGT CAA GTC CAG CTC CAA GAG TCC GGA CCA GGC TTG GTC AGA
CCT AGC CAG ACG CTT AGC TTG ACA TGT ACG GTG AGT GGC TAT TCA ATT
ACA TCC GAT CAT GCT TGG AGC TGG GTC CGG CAA CCT CCA GGC AGA GGA
TTG GAG TGG ATT GGT TAT ATC TCT TAT TCT GGT ATT ACC ACA TAT AAC
CCA TCA CTC AAA AGT CGG GTT ACT ATG CTG CGG GAC ACC TCC AAA AAC
CAA TTT TCC CTT CGG CTG TCA TCA GTG ACC GCG GCG GAT ACA GCG GTG
TAT TAT TGT GCG CGC AGC TTG GCC CGC ACA ACT GCA ATG GAT TAC TGG
GGT CAA GGT TCT CTT GTT ACT GTT AGT TCA GAT AAA ACT CAT ACG TGT
CCC CCT TGT CCA GCA CCA GAA TTG CTG GGA GGC CCC TCT GTG TTT TTG

TTT CCT CCC AAG CCA AAA GAC ACC CTT ATG ATC AGT CGG ACT CCA GAA
GTC ACG TGC GTT GTG GTT GAT GTG TCA CAC GAG GAT CCA GAA GTG AAA
TTC AAC TGG TAC GTT GAT GGC GTT GAG GTC CAT AAT GCA AAA ACC AAA
CCA AGA GAA GAA CAA TAT AAC AGC ACA TAC CGG GTG GTC TCC GTT CTG
ACT GTG TTG CAC CAG GAC TGG TTG AAT GGT AAG GAA TAT AAG TGC AAG
GTG TCA AAC AAA GCG TTG CCT GCT CCG ATC GAA AAA ACA ATA TCC AAG
GCA AAA GGT CAA CCC CGC GAG CCT CAA GTA TAT ACT CTC CCT CCT AGC
CGC GAC GAG TTG ACA AAG AAC CAG GTT TCC TTG ACA TGT CTT GTC AAA
GGG TTC TAC CCG TCC GAT ATA GCT GTT GAA TGG GAA AGT AAT GGC CAG
CCG GAA AAT AAT TAT AAA ACT ACT CCA CCG GTA CTT GAC TCA GAT GGT
TCA TTC TTC CTT TAC TCC AAA CTT ACA GTT GAC AAA TCC AGG TGG CAA
CAG GGA AAT GTA TTT TCT TGT AGT GTT ATG CAC GAG GCG CTG CAC AAT
CAC TAT ACA CAA AAA AGC CTT TCT CTT AGC CCA GGA GGG GGC TCT GGA
GGG GGT GGG AGT GGC GGT GGC AGC GAC ACC GGA CGA CCG TTC GTA GAG
ATG TAC TCT GAA ATA CCA GAG ATA ATC CAC ATG ACT GAA GGA CGG GAG
CTG GTG ATA CCC TGC AGG GTA ACA TCT CCC AAC ATT ACG GTG ACT CTC
AAG AAG TTC CCT CTT GAT ACA CTG ATT CCG GAT GGT AAA CGG ATC ATA
TGG GAT AGT CGA AAA GGT TTT ATA ATC AGC AAT GCA ACC TAT AAG GAG
ATT GGG CTC TTG ACC TGC GAA GCC ACT GTT AAT GGG CAT CTT TAT AAG
ACG AAC TAT CTT ACC CAT CGC CAG ACA AAC ACC ATT ATA GAT GTG GTT
TTG TCC CCT AGT CAC GGG ATA GAA CTC TCA GTG GGC GAG AAG CTG GTC
CTC AAT TGT ACT GCC AGG ACC GAA CTT AAT GTG GGT ATC GAT TTC AAT
TGG GAA TAT CCA TCT TCA AAA CAC CAA CAC AAA AAG CTC GTT AAC AGG
GAC TTG AAG ACC CAA TCT GGA TCT GAG ATG AAG AAG TTC CTT TCT ACA
TTG ACA ATT GAC GGC GTT ACG CGA AGC GAC CAA GGC TTG TAT ACT TGC
GCA GCG TCA TCC GGT CTG ATG ACC AAA AAA AAC AGC ACT TTT GTA AGA
GTT CAC GAA AAG TAG
(SEQ ID NO: 59) [00248] MPLLLLLPLLWAGALADIQMTQSPSSLSASVGDRVTITCRASQDISSYLN
WYQQKPGKAPKLLIYYTSRLHSGVPSRFSGSGSGTDFTFTISSLQPEDIATYYCQQGN
TLPYTFGQGTKVEIKRGGGGSGGGGSGGGGSQVQLQESGPGLVRPSQTLSLTCTVSG
YSITSDHAWSWVRQPPGRGLEWIGYISYSGITTYNPSLKSRVTMLRDTSKNQFSLRLS
SVTAADTAVYYCARSLARTTAMDYWGQGSLVTVSSDKTHTCPPCPAPELLGGPSVF

LFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYN
STYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPS
RDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLT
VDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGSGGGGSGGGSDTGRPFVE
MYSEIPEIIHMTEGRELVIPCRVTSPNITVTLKKFPLDTLIPDGKRIIWDSRKGFIISNAT
YKEIGLLTCEATVNGHLYKTNYLTHRQTNTIIDVVLSPSHGIELSVGEKLVLNCTART
ELNVGIDFNWEYPSSKHQHKKLVNRDLKTQSGSEMKKFLSTLTIDGVTRSDQGLYTC
AASSGLMTKKNSTFVRVHEK
(SEQ ID NO: 60) [00249] ATG CCG CTG CTT TTG CTG CTC CCC CTG TTG TGG GCG GGT GCA
CTT GCC GAC ATA CAG ATG ACA CAG TCC CCG TCA TCA CTG AGC GCA TCC
GTA GGG GAC CGC GTC ACT ATC ACC TGC CGG GCC TCT CAA GAC ATA TCC
TCT TAC CTT AAC TGG TAC CAA CAA AAG CCA GGG AAG GCC CCG AAA CTC
CTC ATA TAT TAT ACA AGC CGG CTC CAT AGC GGG GTA CCC AGT CGG TTT
AGT GGG TCC GGC TCC GGA ACG GAT TTT ACG TTT ACT ATC AGT AGC CTG
CAG CCG GAG GAC ATT GCC ACG TAC TAT TGT CAG CAG GGA AAT ACT CTC
CCC TAT ACA TTT GGA CAA GGC ACG AAA GTC GAA ATT AAA CGC GGC GGC
GGT GGA TCT GGC GGG GGA GGC TCA GGG GGT GGA GGG AGC CAG GTG CAG
CTC CAG GAA TCT GGG CCA GGG TTG GTA AGO CCC TCC CAG ACT TTG AGT
CTC ACA TGC ACC GTC TCT GGG TAT TCT ATA ACG TCT GAC CAC GCG TGG
AGC TGG GTG CGG CAG CCG CCT GGA CGC GGT CTG GAG TGG ATA GGA TAC
ATC TCT TAC AGT GGC ATC ACT ACG TAC AAT CCG TCA CTT AAG AGC CGC
GTC ACT ATG CTC CGG GAC ACT TCA AAA AAC CAG TTT TCC CTC CGC TTG
TCT AGT GTC ACG GCG GCG GAT ACG GCC GTC TAC TAT TGT GCA CGG TCT
TTG GCA CGA ACA ACT GCG ATG GAC TAT TGG GGC CAA GGT TCC CTC GTG
ACG GTC TCC AGT GGT GGA TCA GGG GGC GGA GGA TCC GGC GGC GGT AGC
GGG GGT GGT GGT TCC GAC ACG GGG AGG CCC TTT GTG GAA ATG TAC AGT
GAA ATA CCA GAG ATT ATT CAT ATG ACG GAG GGA CGG GAA CTC GTA ATA
CCC TGC CGG GTA ACA TCA CCG AAT ATT ACG GTT ACT CTC AAA AAA TTC
CCC CTC GAC ACA CTC ATC CCA GAT GGC AAG AGA ATA ATA TGG GAT AGC
CGG AAA GGC TTT ATC ATC TCT AAC GCG ACC TAT AAA GAG ATA GGC CTG
CTT ACG TGC GAG GCG ACA GTT AAT GGA CAT CTT TAT AAA ACG AAT TAC
CTT ACT CAC CGG CAG ACG AAC ACG ATA ATC GAC GTC GTC CTG AGT CCT

TCC CAT GGC ATA GAG CTT AGC GTG GGA GAG AAG TTG GTC TTG AAT TGC
ACC GCG CGC ACA GAA TTG AAT GTA GGG ATT GAC TTT AAC TGG GAG TAC
CCA TCC TCA AAA CAT CAA CAT AAA AAG CTG GTG AAC CGG GAT TTG AAG
ACT CAG AGC GGA TCT GAG ATG AAA AAG TTC CTG TCA ACT CTC ACC ATC
GAT GGA GTA ACC CGA AGT GAC CAG GGT CTT TAT ACA TGT GCA GCT AGT
TCA GGT CTT ATG ACC AAG AAA AAC TCA ACG TTC GTT CGC GTG CAC GAA
AAG GGT GGC AGC GGT GGG GGA GGG AGC GGT GGA GGG GAC AAG ACC CAT
ACT TGC CCC CCA TGT CCT GCC CCG GAA TTG CTC GGT GGG CCA TCT GTA
TTC CTT TTC CCA CCT AAG CCC AAG GAC ACC CTC ATG ATT AGC CGA ACA
CCG GAA GTA ACT TGC GTT GTC GTA GAT GTG TCT CAC GAG GAT CCC GAA
GTC AAA TTC AAC TGG TAC GTC GAC GGC GTA GAG GTC CAT AAT GCT AAA
ACT AAG CCC CGC GAA GAA CAA TAT AAT TCC ACG TAC CGA GTA GTG AGT
GTG CTT ACC GTG CTT CAC CAG GAC TGG TTG AAC GGA AAG GAG TAC AAG
TGT AAG GTT AGC AAC AAG GCG CTC CCG GCT CCG ATA GAA AAG ACT ATC
TCA AAG GCC AAA GGG CAG CCA AGG GAG CCG CAG GTG TAC ACA TTG CCT
CCC TCA AGG GAT GAG CTT ACT AAA AAC CAA GTC TCT CTC ACC TGT CTC
GTA AAG GGG TTT TAT CCC TCT GAT ATC GCT GTG GAA TGG GAA AGT AAC
GGG CAA CCA GAA AAT AAT TAC AAA ACG ACT CCG CCG GTA CTG GAT AGT
GAC GGT AGC TTC TTT TTG TAC AGC AAG TTG ACA GTA GAT AAA TCT AGG
TGG CAA CAA GGT AAC GTA TTT TCC TGC TCA GTA ATG CAC GAA GCG CTG
CAC AAC CAT TAC ACT CAA AAA AGT CTG TCA TTG TCC CCT GGC TAG
(SEQ ID NO: 61) [00250] MPLLLLLPLLWAGALADIQMTQSPSSLSASVGDRVTITCRASQDISSYLN
WYQQKPGKAPKLLIYYTSRLHSGVPSRFSGSGSGTDFTFTISSLQPEDIATYYCQQGN
TLPYTFGQGTKVEIKRGGGGSGGGGSGGGGSQVQLQESGPGLVRPSQTLSLTCTVSG
Y SIT SDHAW SWVRQPPGRGLEWIGYIS Y S GIT TYNP SLKSRVTMLRDTSKNQF SLRLS
SVTAADTAVYYCARSLARTTAMDYWGQGSLVTVSSGGSGGGGSGGGSGGGGSDTG
RPFVEMYSEIPEIIHMTEGRELVIPCRVTSPNITVTLKKFPLDTLIPDGKRIIWDSRKGFII
SNATYKEIGLLTCEATVNGHLYKTNYLTHRQTNTIIDVVLSPSHGIELSVGEKLVLNC
TARTELNVGIDFNWEYPSSKHQHKKLVNRDLKTQSGSEMKKFLSTLTIDGVTRSDQG
LYTCAASSGLMTKKNSTFVRVHEKGGSGGGGSGGGDKTHTCPPCPAPELLGGPSVFL
FPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNS
TYRVV S VLTVLHQDWLNGKEYKCKV SNKALPAPIEKTISKAKGQPREP QVYTLPP SR

DELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTV
DKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG
(SEQ ID NO: 62) [00251] ATG CCA TTG CTT CTC TTG CTG CCA CTC CTT TGG GCT GGA GCC
CTC GCT GAC ATT CAA ATG ACC CAG AGT CCG TCT TCA CTT TCT GCC TCC
GTT GGG GAT AGA GTG ACG ATC ACG TGC CGC GCG TCA CAA GAC ATC TCT
AGT TAC CTC AAC TGG TAT CAG CAA AAG CCC GGT AAA GCT CCA AAA CTT
CTC ATC TAC TAT ACT TCT AGA TTG CAC TCC GGC GTA CCG TCT AGG TTT
TCA GGT AGT GGT AGC GGC ACC GAC TTC ACT TTT ACG ATA TCC TCT TTG
CAG CCC GAG GAT ATC GCT ACT TAC TAT TGT CAA CAA GGA AAC ACG CTT
CCG TAC ACC TTC GGT CAA GGG ACC AAG GTA GAA ATC AAA AGG GGT GGC
GGT GGA TCA GGT GGC GGG GGA TCC GGA GGG GGT GGA TCC CAG GTA CAA
TTG CAA GAG TCT GGC CCC GGT CTC GTC AGG CCA TCC CAA ACT TTG TCA
CTG ACT TGT ACG GTT AGC GGT TAC AGT ATA ACC AGC GAT CAC GCG TGG
AGC TGG GTC CGA CAG CCC CCC GGG CGG GGA TTG GAA TGG ATC GGG TAT
ATC TCC TAC TCA GGA ATA ACC ACT TAC AAT CCA TCC CTG AAA TCC CGA
GTT ACG ATG CTT AGG GAT ACA AGT AAA AAC CAG TTC TCT CTG AGG CTT
AGC TCT GTG ACT GCC GCC GAC ACA GCG GTT TAT TAC TGT GCA CGG TCA
CTG GCG AGG ACC ACG GCG ATG GAC TAT TGG GGC CAG GGA TCA CTC GTG
ACT GTA AGC TCA GGG GGG TCA GGA GGT GGT GGC TCA GGT GGT GGA AGT
GGT GGG GGC GGG TCA GAC ACG GGA AGG CCG TTT GTA GAA ATG TAT AGT
GAG ATA CCG GAA ATT ATA CAC ATG ACC GAA GGC CGA GAA CTC GTC ATA
CCC TGC AGA GTT ACT TCA CCT AAC ATA ACG GTC ACG CTT AAA AAA TTT
CCC CTG GAC ACC CTG ATA CCT GAC GGG AAA CGG ATC ATA TGG GAC TCA
AGG AAA GGG TTT ATC ATC TCC AAT GCT ACT TAT AAA GAG ATC GGG CTC
CTG ACT TGT GAA GCC ACC GTA AAC GGT CAT CTT TAT AAG ACC AAC TAC
CTC ACT CAT CGA CAG ACG AAT ACG ATA ATT GAT GTC GTG CTT AGT CCA
AGC CAC GGT ATT GAG TTG TCA GTG GGC GAG AAA CTG GTG CTC AAT TGC
ACA GCA AGA ACG GAG CTT AAC GTG GGT ATA GAC TTC AAC TGG GAG TAT
CCC TCC AGT AAA CAC CAA CAC AAA AAA CTC GTT AAT AGA GAT TTG AAG
ACC CAA AGC GGA TCA GAG ATG AAG AAA TTT TTG AGC ACT CTC ACG ATA
GAT GGC GTG ACG CGG TCA GAT CAG GGG CTC TAT ACC TGC GCT GCC TCC
TCC GGT CTC ATG ACA AAA AAG AAT AGC ACT TTT GTT AGG GTG CAC GAA

AAA GGC GGC AGC GGA GGG GGG GGA TCA GGT GGT GGA GAC AAG ACA CAT
ACT TGC CCA CCG TGT CCC GCT CCG GAA CTG CTT GGC GGG CCT AGC GTC
TTC CTC TTC CCG CCT AAG CCG AAA GAC ACC CTT ATG ATC TCA CGA ACG
CCC GAG GTG ACG TGC GTC GTT GTT GAT GTG AGC CAC GAA GAT CCA GAA
GTT AAG TTC AAT TGG TAC GTC GAC GGG GTG GAA GTA CAC AAT GCG AAG
ACC AAA CCG AGG GAG GAG CAG TAT AAT TCA ACA TAC AGA GTC GTT TCT
GTC CTC ACG GTT CTC CAC CAG GAT TGG TTG AAC GGC AAA GAA TAT AAA
TGC AAA GTG AGC AAT AAG GCT CTC CCC GCT CCC ATC GAA AAG ACA ATC
TCT AAG GCT AAA GGC CAG CCG AGA GAA CCG CAG GTT TAT ACC CTC CCA
CCC TCA CGC GAC GAG TTG ACT AAG AAC CAG GTC AGC CTT ACG TGT TTG
GTG AAG GGG TTC TAT CCG TCT GAC ATC GCG GTC GAA TGG GAA TCT AAC
GGT CAA CCC GAG AAT AAC TAT AAA ACT ACC CCA CCA GTT TTG GAC TCA
GAC GGG TCC TTT TTC CTG TAC AGC AAG CTC ACG GTC GAC AAA TCC CGG
TGG CAG CAG GGA AAT GTT TTC AGT TGC AGT GTC ATG CAC GAA GCA TTG
CAT AAT CAT TAC ACA CAA AAA TCA CTC AGC CTG AGC CCT GGG GGG GGT
AGT GGC GGG GGA GGA AGC GGT GGA GGA TAC TCT ATG ACT CCG CCA ACA
CTT AAC ATT ACT GAG GAG AGC CAC GTC ATT GAT ACG GGG GAC TCT TTG
TCC ATT TCC TGC AGA GGC CAG CAT CCG CTC GAA TGG GCC TGG CCC GGA
GCT CAA GAG GCC CCG GCG ACT GGT GAT AAA GAC AGC GAG GAT ACG GGA
GTA GTA AGA GAC TGC GAG GGC ACT GAC GCC CGA CCG TAC TGC AAG GTA
CTC CTC CTC CAT GAA GTC CAT GCT AAT GAT ACA GGG AGT TAC GTC TGT
TAC TAC AAA TAC ATC AAA GCG AGG ATA GAA GGT ACG ACC GCG GCT TCA
TCT TAC GTT TTT GTT AGA GAT TTT GAG CAA CCC TTT ATA AAT AAA CCC
GAT ACC CTC CTG GTC AAT CGC AAG GAC GCC ATG TGG GTC CCG TGC CTG
GTG TCA ATC CCA GGA CTT AAC GTC ACT CTC AGA TCT CAA AGC TCT GTG
CTT TGG CCT GAC GGA CAG GAG GTT GTT TGG GAC GAC AGA CGG GGC ATG
CTC GTG TCA ACC CCT CTG CTT CAT GAT GCC CTC TAT TTG CAG TGT GAG
ACG ACG TGG GGT GAC CAG GAT TTT CTG TCA AAC CCT TTT CTG GTG CAC
ATC ACG GGC AAT GAG CTC TAG
(SEQ ID NO: 63) [00252] MPLLLLLPLLWAGALADIQMTQSPSSLSASVGDRVTITCRASQDISSYLN
WYQQKPGKAPKLLIYYTSRLHSGVPSRFSGSGSGTDFTFTISSLQPEDIATYYCQQGN
TLPYTFGQGTKVEIKRGGGGSGGGGSGGGGSQVQLQESGPGLVRPSQTLSLTCTVSG

Y SIT SDHAW SWVRQPPGRGLEWIGYIS Y S GIT TYNP SLKSRVTMLRDTSKNQF SLRLS
SVTAADTAVYYCARSLARTTAMDYWGQGSLVTVSSGGSGGGGSGGGSGGGGSDTG
RPFVEMYSEIPEIIHMTEGRELVIPCRVTSPNITVTLKKFPLDTLIPDGKRIIWDSRKGFII
SNATYKEIGLLTCEATVNGHLYKTNYLTHRQTNTIIDVVLSPSHGIELSVGEKLVLNC
TARTELNVGIDFNWEYPSSKHQHKKLVNRDLKTQSGSEMKKFLSTLTIDGVTRSDQG
LYTCAASSGLMTKKNSTFVRVHEKGGSGGGGSGGGDKTHTCPPCPAPELLGGPSVFL
FPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNS
TYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSR
DELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTV
DKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGSGGGGSGGGYSMTPPTLNIT
EESHVIDTGDSLSISCRGQHPLEWAWPGAQEAPATGDKDSEDTGVVRDCEGTDARP
YCKVLLLHEVHANDTGSYVCYYKYIKARIEGTTAASSYVFVRDFEQPFINKPDTLLV
NRKDAMWVPCLVSIPGLNVTLRSQSSVLWPDGQEVVWDDRRGMLVSTPLLHDALY
LQCETTWGDQDFLSNPFLVHITGNEL
(SEQ ID NO: 64) [00253] ATG CCG CTG CTG TTG CTT CTT CCC CTG CTC TGG GCT GGG GCA
CTG GCC GAC ATA CAA ATG ACC CAG TCA CCA AGT AGT CTC TCT GCA AGC
GTC GGA GAC CGG GTC ACG ATA ACC TGT CGA GCA AGT CAG GAC ATT AGT
AGC TAC CTG AAC TGG TAT CAG CAG AAG CCT GGC AAA GCC CCG AAG CTC
CTC ATA TAC TAT ACC AGC AGA CTG CAC AGT GGT GTA CCA TCC CGA TTC
TCC GGC TCA GGA TCC GGA ACC GAC TTC ACG TTC ACC ATA AGC AGT CTT
CAA CCC GAG GAC ATC GCA ACT TAT TAC TGT CAA CAA GGT AAC ACA CTT
CCA TAT ACA TTC GGC CAG GGT ACC AAA GTT GAG ATC AAA AGA GGA GGC
GGT GGT TCC GGG GGT GGA GGC TCT GGA GGT GGC GGA TCC CAG GTC CAG
CTC CAG GAA AGC GGT CCG GGT TTG GTG AGA CCA TCT CAG ACA CTG AGC
TTG ACG TGT ACG GTA AGT GGT TAC TCT ATA ACT TCC GAT CAT GCG TGG
TCC TGG GTA CGG CAA CCC CCT GGC AGA GGT CTC GAA TGG ATA GGC TAT
ATT AGC TAT TCT GGA ATT ACC ACA TAC AAC CCA AGC CTG AAA TCT CGC
GTC ACC ATG CTG CGC GAT ACT TCC AAG AAT CAA TTT TCT CTG CGG TTG
TCA AGT GTT ACG GCG GCT GAC ACT GCC GTC TAC TAC TGT GCT CGA TCC
CTC GCG CGG ACA ACA GCC ATG GAT TAC TGG GGC CAA GGG TCC CTT GTG
ACG GTA TCC TCC GGC GGG AGT GGT GGC GGG GGT TCC GGG GGA GGT AGT
GGT GGG GGG GGT TCA GAC ACA GGA CGC CCA TTT GTC GAG ATG TAC AGT

GAG ATA CCT GAA ATA ATT CAC ATG ACG GAA GGA CGC GAG CTT GTC ATA
CCA TGC CGC GTG ACT AGC CCT AAT ATT ACG GTA ACA CTG AAA AAA TTC
CCA CTT GAT ACT CTG ATT CCG GAC GGC AAG CGA ATC ATT TGG GAC TCA
AGG AAA GGT TTC ATA ATA TCC AAC GCA ACA TAT AAG GAA ATC GGA CTC
CTG ACG TGC GAG GCG ACG GTA AAC GGC CAC CTT TAT AAG ACA AAC TAT
CTT ACG CAC CGG CAA ACT AAT ACT ATT ATA GAC GTT GTC CTT TCT CCC
TCT CAC GGC ATA GAG TTG AGT GTC GGT GAA AAA TTG GTA CTT AAT TGC
ACC GCG AGA ACG GAA CTT AAT GTC GGA ATT GAT TTC AAT TGG GAA TAC
CCA AGT AGT AAA CAC CAG CAT AAG AAG CTT GTA AAC CGC GAT TTG AAA
ACG CAA TCT GGA TCA GAA ATG AAA AAA TTT CTC AGT ACG CTT ACA ATA
GAT GGG GTA ACC CGA AGC GAT CAA GGA CTG TAT ACC TGC GCA GCG TCT
AGT GGC CTC ATG ACA AAG AAG AAT TCA ACA TTC GTA AGA GTT CAC GAG
AAG GGT GGC GGT GGT TCA GGT GGG GGA TCA GGC GGG GGC GGT TAT AGC
ATG ACG CCC CCG ACA TTG AAC ATT ACA GAA GAG TCT CAC GTA ATA GAT
ACG GGG GAT TCC CTC AGT ATT TCC TGC CGC GGG CAA CAC CCA CTT GAA
TGG GCG TGG CCC GGG GCT CAA GAA GCA CCA GCA ACC GGA GAC AAA GAT
AGC GAG GAT ACT GGT GTC GTT CGA GAC TGT GAA GGG ACC GAT GCC CGG
CCG TAC TGT AAG GTT CTC CTG TTG CAT GAG GTT CAT GCT AAT GAT ACG
GGC AGC TAT GTG TGC TAC TAT AAG TAC ATC AAA GCG CGG ATC GAA GGC
ACT ACC GCC GCG TCT TCT TAT GTT TTC GTG CGA GAT TTT GAA CAA CCA
TTT ATA AAC AAG CCG GAC ACT TTG CTC GTC AAT AGG AAA GAC GCC ATG
TGG GTT CCC TGC TTG GTG TCC ATA CCC GGC CTG AAT GTT ACA CTT AGG
TCA CAG AGC TCT GTT TTG TGG CCT GAC GGA CAG GAG GTT GTT TGG GAT
GAT AGA CGA GGC ATG CTC GTG TCA ACT CCA CTT CTT CAC GAT GCG CTG
TAT CTC CAA TGC GAG ACT ACG TGG GGA GAT CAA GAC TTT CTT AGC AAT
CCC TTC CTG GTC CAC ATT ACT GGA AAT GAG CTT GGT GGG AGC GGA GGT
GGG GGC TCA GGA GGT GGG GAT AAG ACC CAT ACT TGC CCA CCC TGC CCG
GCA CCT GAA CTT CTC GGA GGT CCG TCA GTG TTT TTG TTT CCG CCA AAG
CCT AAA GAC ACA CTG ATG ATT TCT CGG ACG CCC GAG GTA ACT TGT GTA
GTC GTA GAC GTG TCC CAT GAG GAC CCT GAA GTT AAA TTC AAC TGG
TACGTG GAC GGG GTT GAA GTA CAT AAT GCA AAG ACA AAA CCC CGG GAG
GAG CAG TAT AAC AGT ACT TAC AGA GTA GTC TCC GTG CTC ACC GTA CTC
CAC CAA GAT TGG CTC AAC GGC AAG GAG TAC AAA TGC AAA GTG TCA AAT
AAA GCG TTG CCT GCT CCA ATT GAA AAA ACA ATA TCC AAG GCG AAG GGG

CAA CCC CGA GAG CCT CAG GTT TAC ACA TTG CCG CCA AGT CGA GAC GAA
TTG ACA AAG AAC CAA GTT AGC TTG ACC TGC CTC GTG AAG GGT TTT TAT
CCG AGC GAT ATA GCC GTT GAA TGG GAG TCT AAC GGG CAA CCG GAA AAT
AAC TAT AAA ACC ACT CCG CCG GTG CTT GAC AGC GAC GGT TCT TTT TTC
CTG TAC AGT AAA CTC ACC GTT GAT AAA TCT AGG TGG CAG CAG GGT AAC
GTC TTT AGT TGC AGC GTT ATG CAT GAG GCT CTT CAT AAT CAT TAT ACT
CAA AAA TCT TTG AGT CTG TCT CCC GGA TAG
(SEQ ID NO: 65) [00254] MPLLLLLPLLWAGALADIQMTQ SP S SL S A S VGDRVTIT CRA S QDI S SYLN
WYQQKPGKAPKLLIYYT SRLHSGVP SRF S GS GS GTDF TF TIS SLQPEDIATYYCQQGN
TLPYTF GQ GTKVEIKRGGGGS GGGGS GGGGS QVQLQE S GP GLVRP SQTL SLT C TV S G
Y S IT SDHAW SWVRQPPGRGLEWIGYI S Y S GIT TYNP SLKSRVTMLRDTSKNQF SLRLS
S VTAAD TAVYYC ARSLARTTAMD YWGQ GSLVT VS SGGSGGGGSGGGSGGGGSDTG
RPFVEMYSEIPEIIHMTEGRELVIPCRVT SPNITVTLKKFPLDTLIPDGKRIIWD SRKGF II
SNATYKEIGLLTCEATVNGHLYKTNYLTHRQTNTIIDVVL SP SHGIEL SVGEKLVLNC
TARTELNVGIDFNWEYP S SKHQHKKLVNRDLKTQ SGSEMKKFL S TLTID GVTR SD Q G
LYTC AA S SGLMTKKNSTFVRVHEKGGGGSGGGSGGGGYSMTPPTLNITEESHVIDTG
D SL S I S CRGQHPLEWAWP GAQEAPAT GDKD SEDTGVVRDCEGTDARPYCKVLLLHE
VHAND T GS YVC YYKYIKARIEGTTAA S SYVFVRDFEQPFINKPDTLLVNRKDAMWV
P CLV S IP GLNVTLRS Q S SVLWPDGQEVVWDDRRGMLVSTPLLHDALYLQCETTWGD
QDFL SNPFLVHITGNELGGS GGGGS GGGDK THT CPP CPAPELLGGP SVFLFPPKPKDT
LMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVL
TVLHQDWLNGKEYKCKV SNKALPAP IEKTI SKAK GQPREP QVYTLPP SRDELTKNQV
SLTCLVKGFYP SDIAVEWESNGQPENNYKTTPPVLD SDGSFFLYSKLTVDKSRWQQG
NVF SC SVMHEALHNHYTQK SLSL SP G
(SEQ ID NO: 66) [00255] GGG GGC GGT GGC AGT GGT GGA GGG GGT AGC GGA GGC GGG GGG AGT
(SEQ ID NO: 67) [00256] GGGGSGGGGSGGGGS (SEQ ID NO: 68) [00257] GGT GGA TCA GGG GGC GGA GGA TCC GGC GGC GGT AGC GGG GGT
GGT GGT
(SEQ ID NO: 69) [00258] GGSGGGGSGGGSGGGG (SEQ ID NO: 70) [00259] GGT GGC GGT GGT TCA GGT GGG GGA TCA GGC GGG GGC GGT
(SEQ ID NO: 71) [00260] GGGGSGGGSGGGG (SEQ ID NO: 72) [00261] EVQLVESGGGLVQPGGSLRL S CAA S GS VFKINVMAWYRQAPGK GRELV
AGIISGGSTSYAD SVKGRF TISRDNAKNTLYLQMNSLRPEDTAVYYCAFITTESDYDL
GRRYWGQGTLVTVS S
(SEQ ID NO: 73) [00262] MPLLLLLPLLWAGALADIQMTQ SP S SL SAS VGDRVTIT CRASQDIS SYLN
WYQQKPGKAPKLLIYYT SRLHSGVP SRF S GS GS GTDF TFTIS SLQPEDIATYYCQQGN
TLPYTF GQ GTKVEIKRGGGGS GGGGS GGGGS QVQLQE S GP GLVRP SQTL SLT C TV S G
Y S IT SDHAW SWVRQPPGRGLEWIGYI S Y S GIT TYNP SLKSRVTMLRDTSKNQF SLRLS
SVTAADTAVYYCARSLARTTAMDYWGQGSLVTVS SDKTHTCPPCPAPELLGGPS VF
LFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYN
S TYRVV S VLTVLHQDWLNGKEYKCKV SNKALPAPIEKTI SKAKGQPREP QVYTLPP S
RDELTKNQV SLT CLVKGF YP S DIAVEWE SNGQPENNYKT TPPVLD SD GSFFLY SKLT
VDKSRWQQGNVF SC SVMHEALHNHYTQKSLSLSPGGGSGGGSGGGGSGGGGGSGG
GGSDTGRPFVEMYSEIPEIIHMTEGRELVIPCRVTSPNITVTLKKFPLDTLIPDGKRIIW
D SRKGF II SNATYKEIGLLTCEATVNGHLYKTNYLTHRQ TNTIIDVVL SP SHGIEL S VG
EKLVLNCTARTELNVGIDFNWEYP S SKHQHKKLVNRDLKTQ SGSEMKKFL STLTIDG
VTR SD Q GLYT CAA S SGLMTKKNSTFVRVHEK
(SEQ ID NO: 74) [00263] ATGCCGCTCTTGCTCCTTCTTCCATTGCTCTGGGCGGGCGCACTGGCC
GATAT C C AAATGAC GC AAAGTC C AAGTT C TC TT TC AGC C AGC GT C GGAGATAGA
GTC AC TATAAC ATGC C GC GC GAGC CAGGATATATC AAGC TAC C T TAAT TGGTAT C

AACAAAAACCGGGTAAAGCGCCGAAACTCTTGATTTATTATACCAGTAGGCTCC
ACTCCGGTGTACCAAGTCGGTTCAGTGGCTCCGGGAGTGGAACCGACTTCACATT
TACAATAAGCTCTTTGCAACCAGAGGATATTGCAACTTACTATTGCCAGCAAGGC
AACACGTTGCCTTACACGTTTGGACAGGGAACAAAGGTTGAGATAAAGCGAGGG
GGCGGTGGCAGTGGTGGAGGGGGTAGCGGAGGCGGGGGGAGTCAAGTCCAGCT
CCAAGAGTCCGGACCAGGCTTGGTCAGACCTAGCCAGACGCTTAGCTTGACATGT
ACGGTGAGTGGCTATTCAATTACATCCGATCATGCTTGGAGCTGGGTCCGGCAAC
CTCCAGGCAGAGGATTGGAGTGGATTGGTTATATCTCTTATTCTGGTATTACCAC
ATATAACCCATCACTCAAAAGTCGGGTTACTATGCTGCGGGACACCTCCAAAAAC
CAATTTTCCCTTCGGCTGTCATCAGTGACCGCGGCGGATACAGCGGTGTATTATT
GTGCGCGCAGCTTGGCCCGCACAACTGCAATGGATTACTGGGGTCAAGGTTCTCT
TGTTACTGTTAGTTCAGATAAAACTCATACGTGTCCCCCTTGTCCAGCACCAGAA
TTGCTGGGAGGCCCCTCTGTGTTTTTGTTTCCTCCCAAGCCAAAAGACACCCTTAT
GATCAGTCGGACTCCAGAAGTCACGTGCGTTGTGGTTGATGTGTCACACGAGGAT
CCAGAAGTGAAATTCAACTGGTACGTTGATGGCGTTGAGGTCCATAATGCAAAA
ACCAAACCAAGAGAAGAACAATATAACAGCACATACCGGGTGGTCTCCGTTCTG
ACTGTGTTGCACCAGGACTGGTTGAATGGTAAGGAATATAAGTGCAAGGTGTCA
AACAAAGCGTTGCCTGCTCCGATCGAAAAAACAATATCCAAGGCAAAAGGTCAA
CCCCGCGAGCCTCAAGTATATACTCTCCCTCCTAGCCGCGACGAGTTGACAAAGA
ACCAGGTTTCCTTGACATGTCTTGTCAAAGGGTTCTACCCGTCCGATATAGCTGTT
GAATGGGAAAGTAATGGCCAGCCGGAAAATAATTATAAAACTACTCCACCGGTA
CTTGACTCAGATGGTTCATTCTTCCTTTACTCCAAACTTACAGTTGACAAATCCAG
GTGGCAACAGGGAAATGTATTTTCTTGTAGTGTTATGCACGAGGCGCTGCACAAT
CACTATACACAAAAAAGCCTTTCTCTTAGCCCAGGAGGGGGCTCTGGAGGAGGA
AGCGGCGGAGGCGGAAGCGGAGGGGGAGGTGGCTCCGGAGGCGGTGGCAGCGA
CACCGGACGACCGTTCGTAGAGATGTACTCTGAAATACCAGAGATAATCCACAT
GACTGAAGGACGGGAGCTGGTGATACCCTGCAGGGTAACATCTCCCAACATTAC
GGTGACTCTCAAGAAGTTCCCTCTTGATACACTGATTCCGGATGGTAAACGGATC
ATATGGGATAGTCGAAAAGGTTTTATAATCAGCAATGCAACCTATAAGGAGATT
GGGCTCTTGACCTGCGAAGCCACTGTTAATGGGCATCTTTATAAGACGAACTATC
TTACCCATCGCCAGACAAACACCATTATAGATGTGGTTTTGTCCCCTAGTCACGG
GATAGAACTCTCAGTGGGCGAGAAGCTGGTCCTCAATTGTACTGCCAGGACCGA
ACTTAATGTGGGTATCGATTTCAATTGGGAATATCCATCTTCAAAACACCAACAC
AAAAAGCTCGTTAACAGGGACTTGAAGACCCAATCTGGATCTGAGATGAAGAAG

TTCCTTTCTACATTGACAATTGACGGCGTTACGCGAAGCGACCAAGGCTTGTATA
CTTGCGCAGCGTCATCCGGTCTGATGACCAAAAAAAACAGCACTTTTGTAAGAGT
TCACGAAAAG
(SEQ ID NO: 75) [00264] MPLLLLLPLLWAGALASDTGRPFVEMYSEIPEIIHMTEGRELVIPCRVTSP
NITVTLKKFPLDTLIPDGKRIIWDSRKGFIISNATYKEIGLLTCEATVNGHLYKTNYLT
HRQTNTIIDVVLSPSHGIELSVGEKLVLNCTARTELNVGIDFNWEYPSSKHQHKKLVN
RDLKTQSGSEMKKFLSTLTIDGVTRSDQGLYTCAASSGLMTKKNSTFVRVHEKDKT
HTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVD
GVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTI
SKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKT
TPPVLD SDGSFFLYSKLTVDKSRWQQGNVF SC S VMHEALHNHYT QK SL SL SP GGGS
GGGSGGGGSGGGGGSGGGGDIQMTQSPSSLSASVGDRVTITCRASQDISSYLNWYQ
QKPGKAPKLLIYYTSRLHSGVPSRFSGSGSGTDFTFTISSLQPEDIATYYCQQGNTLPY
TFGQGTKVEIKRGGGGSGGGGSGGGGSQVQLQESGPGLVRPSQTLSLTCTVSGYSITS
DHAWSWVRQPPGRGLEWIGYISYSGITTYNP SLKSRVTMLRDT SKNQF SLRLS SVTA
ADTAVYYCARSLARTTAMDYWGQGSLVTVSS
(SEQ ID NO: 76) [00265] ATGCCGCTCTTGCTCCTTCTTCCATTGCTCTGGGCGGGCGCACTGGCC
AGCGACACCGGACGACCGTTCGTAGAGATGTACTCTGAAATACCAGAGATAATC
CACATGACTGAAGGACGGGAGCTGGTGATACCCTGCAGGGTAACATCTCCCAAC
ATTACGGTGACTCTCAAGAAGTTCCCTCTTGATACACTGATTCCGGATGGTAAAC
GGATCATATGGGATAGTCGAAAAGGTTTTATAATCAGCAATGCAACCTATAAGG
AGATTGGGCTCTTGACCTGCGAAGCCACTGTTAATGGGCATCTTTATAAGACGAA
CTATCTTACCCATCGCCAGACAAACACCATTATAGATGTGGTTTTGTCCCCTAGTC
ACGGGATAGAACTCTCAGTGGGCGAGAAGCTGGTCCTCAATTGTACTGCCAGGA
CCGAACTTAATGTGGGTATCGATTTCAATTGGGAATATCCATCTTCAAAACACCA
ACACAAAAAGCTCGTTAACAGGGACTTGAAGACCCAATCTGGATCTGAGATGAA
GAAGTTCCTTTCTACATTGACAATTGACGGCGTTACGCGAAGCGACCAAGGCTTG
TATACTTGCGCAGCGTCATCCGGTCTGATGACCAAAAAAAACAGCACTTTTGTAA

GAGTTCACGAAAAGGATAAAACTCATACGTGTCCCCCTTGTCCAGCACCAGAATT
GCTGGGAGGCCCCTCTGTGTTTTTGTTTCCTCCCAAGCCAAAAGACACCCTTATG
ATCAGTCGGACTCCAGAAGTCACGTGCGTTGTGGTTGATGTGTCACACGAGGATC
CAGAAGTGAAATTCAACTGGTACGTTGATGGCGTTGAGGTCCATAATGCAAAAA
CCAAACCAAGAGAAGAACAATATAACAGCACATACCGGGTGGTCTCCGTTCTGA
CTGTGTTGCACCAGGACTGGTTGAATGGTAAGGAATATAAGTGCAAGGTGTCAA
ACAAAGCGTTGCCTGCTCCGATCGAAAAAACAATATCCAAGGCAAAAGGTCAAC
CCCGCGAGCCTCAAGTATATACTCTCCCTCCTAGCCGCGACGAGTTGACAAAGAA
CCAGGTTTCCTTGACATGTCTTGTCAAAGGGTTCTACCCGTCCGATATAGCTGTTG
AATGGGAAAGTAATGGCCAGCCGGAAAATAATTATAAAACTACTCCACCGGTAC
TTGACTCAGATGGTTCATTCTTCCTTTACTCCAAACTTACAGTTGACAAATCCAGG
TGGCAACAGGGAAATGTATTTTCTTGTAGTGTTATGCACGAGGCGCTGCACAATC
ACTATACACAAAAAAGCCTTTCTCTTAGCCCAGGAGGGGGCTCTGGAGGAGGAA
GCGGCGGAGGCGGAAGCGGAGGGGGAGGTGGCTCCGGAGGCGGTGGCGATATC
CAAATGACGCAAAGTCCAAGTTCTCTTTCAGCCAGCGTCGGAGATAGAGTCACTA
TAACATGCCGCGCGAGCCAGGATATATCAAGCTACCTTAATTGGTATCAACAAA
AACCGGGTAAAGCGCCGAAACTCTTGATTTATTATACCAGTAGGCTCCACTCCGG
TGTACCAAGTCGGTTCAGTGGCTCCGGGAGTGGAACCGACTTCACATTTACAATA
AGCTCTTTGCAACCAGAGGATATTGCAACTTACTATTGCCAGCAAGGCAACACGT
TGCCTTACACGTTTGGACAGGGAACAAAGGTTGAGATAAAGCGAGGGGGCGGTG
GCAGTGGTGGAGGGGGTAGCGGAGGCGGGGGGAGTCAAGTCCAGCTCCAAGAG
TCCGGACCAGGCTTGGTCAGACCTAGCCAGACGCTTAGCTTGACATGTACGGTGA
GTGGCTATTCAATTACATCCGATCATGCTTGGAGCTGGGTCCGGCAACCTCCAGG
CAGAGGATTGGAGTGGATTGGTTATATCTCTTATTCTGGTATTACCACATATAAC
CCATCACTCAAAAGTCGGGTTACTATGCTGCGGGACACCTCCAAAAACCAATTTT
CCCTTCGGCTGTCATCAGTGACCGCGGCGGATACAGCGGTGTATTATTGTGCGCG
CAGCTTGGCCCGCACAACTGCAATGGATTACTGGGGTCAAGGTTCTCTTGTTACT
GTTAGTTCA
(SEQ ID NO: 77) [00266] SDTGRPFVEMYSEIPEIIHMTEGRELVIPCRVT SPNITVTLKKFPLDTLIPDG
KRIIWDSRKGFIISNATYKEIGLLTCEATVNGHLYKTNYLTHRQTNTIIDVVLSPSHGIE
LSVGEKLVLNCTARTELNVGIDFNWEYP S SKHQHKKLVNRDLKTQ SGSEMKKFLS T

LTIDGVTRSDQGLYTCAAS SGLMTKKNSTFVRVHEKQVQLQESGPGLVRP SQTLSLT
CTVSGYSITSDHAWSWVRQPPGRGLEWIGYISYSGITTYNP SLKSRVTMLRDTSKNQF
SLRLS SVTAADTAVYYCARSLARTTAMDYWGQGSLVTVS SASTKGP SVFPLAPS SKS
TSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSS
LGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGP SVFLFPPKPKDT
LMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVL
TVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPP SREEMTKNQ
VSLTCLVKGFYP SDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQ
GNVF SC SVMHEALHNHYTQKSLSLSP
(SEQ ID NO: 78) [00267] AGCGACACCGGCAGACCCTTCGTGGAGATGTACAGCGAGATCCCCGA
GATCATCCACATGACCGAGGGCAGAGAGCTGGTGATCCCCTGCAGAGTGACCAG
CCCCAACATCACCGTGACCCTGAAGAAGTTCCCCCTGGACACCCTGATCCCCGAC
GGCAAGAGAATCATCTGGGACAGCAGAAAGGGCTTCATCATCAGCAACGCCACC
TACAAGGAGATCGGCCTGCTGACCTGCGAGGCCACCGTGAACGGCCACCTGTAC
AAGACCAACTACCTGACCCACAGACAGACCAACACCATCATCGACGTGGTGCTG
AGCCCCAGCCACGGCATCGAGCTGAGCGTGGGCGAGAAGCTGGTGCTGAACTGC
ACCGCCAGAACCGAGCTGAACGTGGGCATCGACTTCAACTGGGAGTACCCCAGC
AGCAAGCACCAGCACAAGAAGCTGGTGAACAGAGACCTGAAGACCCAGAGCGG
CAGCGAGATGAAGAAGTTCCTGAGCACCCTGACCATCGACGGCGTGACCAGAAG
CGACCAGGGCCTGTACACCTGCGCCGCCAGCAGCGGCCTGATGACCAAGAAGAA
CAGCACCTTCGTGAGAGTGCACGAGAAGCAGGTGCAGCTGCAGGAGAGCGGCCC
CGGACTGGTGAGGCCTTCCCAGACCCTGAGCCTGACATGCACAGTGAGCGGCTA
CAGCATCACAAGCGACCACGCCTGGAGCTGGGTGAGACAGCCCCCCGGAAGAGG
CCTGGAATGGATCGGATATATCTCCTACTCAGGCATTACCACCTACAACCCCTCT
CTGAAAAGCAGAGTGACCATGCTGAGAGATACTAGCAAGAACCAGTTTAGCCTG
AGACTGTCTAGCGTGACTGCCGCCGACACCGCCGTGTACTACTGCGCCAGATCCC
TGGCCCGGACCACAGCCATGGATTACTGGGGCCAGGGAAGCCTGGTGACAGTGT
CCTCCGCTAGCACCAAGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAG
CACCTCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAA
CCGGTGACGGTGTCGTGGAACTCAGGCGCCCTGACCAGCGGCGTGCACACCTTCC
CGGCTGTCCTACAGTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCC

CTCCAGCAGCTTGGGCACCCAGACCTACATCTGCAACGTGAATCACAAGCCCAG
CAACACCAAGGTGGACAAGAAAGTTGAGCCCAAATCTTGTGACAAAACTCACAC
ATGCCCACCGTGCCCAGCACCTGAACTCCTGGGGGGACCGTCAGTCTTCCTCTTC
CCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCCCGAGGTCACATGC
GTGGTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTACGTG
GACGGCGTGGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAA
CAGCACGTACCGTGTGGTCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAAT
GGCAAGGAGTACAAGTGCAAGGTCTCCAACAAAGCCCTCCCAGCCCCCATCGAG
AAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAACCACAGGTGTACACCCTG
CCCCCATCCCGGGAGGAGATGACCAAGAACCAGGTCAGCCTGACCTGCCTGGTC
AAAGGCTTCTATCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCG
GAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCC
TCTACAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGGGGAACGTCTTCT
CATGCTCCGTGATGCATGAGGCTCTGCACAACCACTACACGCAGAAGAGCCTCTC
CCTGTCTCCG (SEQ ID NO: 79) [00268] DIQMTQ SP S SLSASVGDRVTITCRASQDIS SYLNWYQQKPGKAPKLLIYYT
SRLHSGVP SRFSGSGSGTDFTF TISSLQPEDIATYYCQQGNTLPYTFGQGTKVEIKRTV
AAP SVFIFPP SDEQLK SGTASVVCLLNNFYPREAKVQWKVDNALQ SGNSQESVTEQD
SKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
(SEQ ID NO: 80) [00269] GACATTCAGATGACCCAGAGCCCCAGCAGCCTGAGCGCCAGCGTGGG
AGACAGAGTGACCATCACCTGCAGAGCCAGCCAGGACATCTCCAGCTACCTGAA
CTGGTATCAGCAGAAACCCGGCAAAGCCCCAAAACTGCTGATCTACTACACCAG
TAGACTGCACAGCGGCGTGCCCAGCAGATTCTCAGGAAGCGGCTCCGGAACCGA
CTTCACCTTCACTATCAGCAGCCTGCAGCCCGAAGATATTGCTACTTACTACTGC
CAGCAGGGGAACACCCTGCCCTATACCTTCGGCCAGGGCACCAAGGTGGAGATC
AAACGTACGGTGGCTGCACCATCTGTCTTCATCTTCCCGCCATCTGATGAGCAGT
TGAAATCTGGAACTGCCTCTGTTGTGTGCCTGCTGAATAACTTCTATCCCAGAGA
GGCCAAAGTACAGTGGAAGGTGGATAACGCCCTCCAATCGGGTAACTCCCAGGA
GAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTCAGCAGCACCCT
GACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTACGCCTGCGAAGTCAC

CCATCAGGGCCTGAGTTCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGT
(SEQ ID NO: 81) [00270] SDTGRPFVEMYSEIPEIIHMTEGRELVIPCRVT SPNITVTLKKFPLDTLIPDG
KRIIWD SRKGFIISNATYKEIGLLTCEATVNGHLYKTNYLTHRQTNTIIDVVL SP SHGIE
L SVGEKLVLNCTARTELNVGIDFNWEYP S SKHQHKKLVNRDLKTQ SGSEMKKFL S T
LTIDGVTRSDQGLYTCAASSGLMTKKNSTFVRVHEKGGSGGGSGGGGSGGGGGSGG
GGQVQLQESGPGLVRP SQTL SLTCTVSGYSITSDHAW SWVRQPPGRGLEWIGYISYS
GITTYNP SLK SRVTMLRDT SKNQF SLRL S SVTAADTAVYYCARSLARTTAMDYWGQ
GSLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGV
HTFPAVLQ S SGLYSL S SVVTVPS S SLGTQTYICNVNHKP SNTKVDKKVEPK SCDKTHT
CPPCPAPELLGGP SVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGV
EVHNAKTKPREEQYNS TYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISK
AKGQPREPQVYTLPP SREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTP
PVLD SD GSFFLY SKL TVDK SRWQQGNVF SC SVMHEALHNHYTQK SL SL SP
(SEQ ID NO: 82) [00271] AGCGACACCGGCAGACCCTTCGTGGAGATGTACAGCGAGATCCCCGA
GATCATCCACATGACCGAGGGCAGAGAGCTGGTGATCCCCTGCAGAGTGACCAG
CCCCAACATCACCGTGACCCTGAAGAAGTTCCCCCTGGACACCCTGATCCCCGAC
GGCAAGAGAATCATCTGGGACAGCAGAAAGGGCTTCATCATCAGCAACGCCACC
TACAAGGAGATCGGCCTGCTGACCTGCGAGGCCACCGTGAACGGCCACCTGTAC
AAGACCAACTACCTGACCCACAGACAGACCAACACCATCATCGACGTGGTGCTG
AGCCCCAGCCACGGCATCGAGCTGAGCGTGGGCGAGAAGCTGGTGCTGAACTGC
ACCGCCAGAACCGAGCTGAACGTGGGCATCGACTTCAACTGGGAGTACCCCAGC
AGCAAGCACCAGCACAAGAAGCTGGTGAACAGAGACCTGAAGACCCAGAGCGG
CAGCGAGATGAAGAAGTTCCTGAGCACCCTGACCATCGACGGCGTGACCAGAAG
CGACCAGGGCCTGTACACCTGCGCCGCCAGCAGCGGCCTGATGACCAAGAAGAA
CAGCACCTTCGTGAGAGTGCACGAGAAGGGAGGAAGCGGAGGAGGAAGCGGGG
GAGGAGGAAGTGGAGGAGGAGGAGGGAGCGGAGGAGGGGGACAGGTGCAGCT
GCAGGAGAGCGGCCCCGGACTGGTGAGGCCTTCCCAGACCCTGAGCCTGACATG
CACAGTGAGCGGCTACAGCATCACAAGCGACCACGCCTGGAGCTGGGTGAGACA
GCCCCCCGGAAGAGGCCTGGAATGGATCGGATATATCTCCTACTCAGGCATTACC
ACCTACAACCCCTCTCTGAAAAGCAGAGTGACCATGCTGAGAGATACTAGCAAG

AACCAGTTTAGCCTGAGACTGTCTAGCGTGACTGCCGCCGACACCGCCGTGTACT
ACTGCGCCAGATCCCTGGCCCGGACCACAGCCATGGATTACTGGGGCCAGGGAA
GCCTGGTGACAGTGTCCTCCGCTAGCACCAAGGGCCCATCGGTCTTCCCCCTGGC
ACCCTCCTCCAAGAGCACCTCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAA
GGACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGCGCCCTGACCAG
CGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCAGGACTCTACTCCCTCAGC
AGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACCCAGACCTACATCTGCAACG
TGAATCACAAGCCCAGCAACACCAAGGTGGACAAGAAAGTTGAGCCCAAATCTT
GTGACAAAACTCACACATGCCCACCGTGCCCAGCACCTGAACTCCTGGGGGGAC
CGTCAGTCTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGAC
CCCCGAGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAA
GTTCAACTGGTACGTGGACGGCGTGGAGGTGCATAATGCCAAGACAAAGCCGCG
GGAGGAGCAGTACAACAGCACGTACCGTGTGGTCAGCGTCCTCACCGTCCTGCA
CCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTCTCCAACAAAGCCCT
CCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAACC
ACAGGTGTACACCCTGCCCCCATCCCGGGAGGAGATGACCAAGAACCAGGTCAG
CCTGACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGTGGAGTGGGAG
AGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCC
GACGGCTCCTTCTTCCTCTACAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGC
AGGGGAACGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCACTACAC
GCAGAAGAGCCTCTCCCTGTCTCCG
(SEQ ID NO: 83) [00272] DIQMTQ SP S SL SAS VGDRVTIT CRAS QDIS SYLNWYQQKPGKAPKLLIYYT
SRLHSGVP SRFSGSGSGTDFTF TISSLQPEDIATYYCQQGNTLPYTF GQGTKVEIKRTV
AAP SVFIFPP SDEQLK SGTASVVCLLNNFYPREAKVQWKVDNALQ SGNSQESVTEQD
SKDSTYSLS STLTLSKADYEKHKVYACEVTHQGLS SPVTKSFNRGEC
(SEQ ID NO: 84) [00273] GACATTCAGATGACCCAGAGCCCCAGCAGCCTGAGCGCCAGCGTGGG
AGACAGAGTGACCATCACCTGCAGAGCCAGCCAGGACATCTCCAGCTACCTGAA
CTGGTATCAGCAGAAACCCGGCAAAGCCCCAAAACTGCTGATCTACTACACCAG

TAGACTGCACAGCGGCGTGCCCAGCAGATTCTCAGGAAGCGGCTCCGGAACCGA
CTTCACCTTCACTATCAGCAGCCTGCAGCCCGAAGATATTGCTACTTACTACTGC
CAGCAGGGGAACACCCTGCCCTATACCTTCGGCCAGGGCACCAAGGTGGAGATC
AAACGTACGGTGGCTGCACCATCTGTCTTCATCTTCCCGCCATCTGATGAGCAGT
TGAAATCTGGAACTGCCTCTGTTGTGTGCCTGCTGAATAACTTCTATCCCAGAGA
GGCCAAAGTACAGTGGAAGGTGGATAACGCCCTCCAATCGGGTAACTCCCAGGA
GAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTCAGCAGCACCCT
GACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTACGCCTGCGAAGTCAC
CCATCAGGGCCTGAGTTCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGT
(SEQ ID NO: 85) [00274] SDTGRPFVEMYSEIPEIIHMTEGRELVIPCRVT SPNITVTLKKFPLDTLIPDG
KRIIWDSRKGFIISNATYKEIGLLTCEATVNGHLYKTNYLTHRQTNTIIDVVLSPSHGIE
LSVGEKLVLNCTARTELNVGIDFNWEYP S SKHQHKKLVNRDLKTQSGSEMKKFLS T
LTIDGVTRSDQGLYTCAAS SGLMTKKNSTFVRVHEKGGSGGGSGGGGSGGGGGSGG
GGQVQLQESGPGLVRP SQTLSLTCTVSGYSITSDHAW SWVRQPPGRGLEWIGYISYS
GITTYNP SLKSRVTMLRDT SKNQF SLRLS SVTAADTAVYYCARSLARTTAMDYWGQ
GSLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGV
HTFPAVLQSSGLYSLSSVVTVPS SSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHT
CPPCPAPELLGGP SVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGV
EVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISK
AKGQPREPQVYTLPP SREEMTKNQ V SLTCL VKGF YP SDIAVEWESNGQPENNYKTTP
PVLDSDGSFFLYSKLTVDKSRWQQGNVF SC SVMHEALHNHYTQK SLSLSPGK
(SEQ ID NO: 86) [00275] AGCGACACCGGCAGACCCTTCGTGGAGATGTACAGCGAGATCCCCGA
GATCATCCACATGACCGAGGGCAGAGAGCTGGTGATCCCCTGCAGAGTGACCAG
CCCCAACATCACCGTGACCCTGAAGAAGTTCCCCCTGGACACCCTGATCCCCGAC
GGCAAGAGAATCATCTGGGACAGCAGAAAGGGCTTCATCATCAGCAACGCCACC
TACAAGGAGATCGGCCTGCTGACCTGCGAGGCCACCGTGAACGGCCACCTGTAC
AAGACCAACTACCTGACCCACAGACAGACCAACACCATCATCGACGTGGTGCTG
AGCCCCAGCCACGGCATCGAGCTGAGCGTGGGCGAGAAGCTGGTGCTGAACTGC
ACCGCCAGAACCGAGCTGAACGTGGGCATCGACTTCAACTGGGAGTACCCCAGC
AGCAAGCACCAGCACAAGAAGCTGGTGAACAGAGACCTGAAGACCCAGAGCGG

CAGCGAGATGAAGAAGTTCCTGAGCACCCTGACCATCGACGGCGTGACCAGAAG
CGACCAGGGCCTGTACACCTGCGCCGCCAGCAGCGGCCTGATGACCAAGAAGAA
CAGCACCTTCGTGAGAGTGCACGAGAAGGGAGGAAGCGGAGGAGGAAGCGGGG
GAGGAGGAAGTGGAGGAGGAGGAGGGAGCGGAGGAGGGGGACAGGTGCAGCT
GCAGGAGAGCGGCCCCGGACTGGTGAGGCCTTCCCAGACCCTGAGCCTGACATG
CACAGTGAGCGGCTACAGCATCACAAGCGACCACGCCTGGAGCTGGGTGAGACA
GCCCCCCGGAAGAGGCCTGGAATGGATCGGATATATCTCCTACTCAGGCATTACC
ACCTACAACCCCTCTCTGAAAAGCAGAGTGACCATGCTGAGAGATACTAGCAAG
AACCAGTTTAGCCTGAGACTGTCTAGCGTGACTGCCGCCGACACCGCCGTGTACT
ACTGCGCCAGATCCCTGGCCCGGACCACAGCCATGGATTACTGGGGCCAGGGAA
GCCTGGTGACAGTGTCCTCCGCTAGCACCAAGGGCCCATCGGTCTTCCCCCTGGC
ACCCTCCTCCAAGAGCACCTCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAA
GGACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGCGCCCTGACCAG
CGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCAGGACTCTACTCCCTCAGC
AGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACCCAGACCTACATCTGCAACG
TGAATCACAAGCCCAGCAACACCAAGGTGGACAAGAAAGTTGAGCCCAAATCTT
GTGACAAAACTCACACATGCCCACCGTGCCCAGCACCTGAACTCCTGGGGGGAC
CGTCAGTCTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGAC
CCCCGAGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAA
GTTCAACTGGTACGTGGACGGCGTGGAGGTGCATAATGCCAAGACAAAGCCGCG
GGAGGAGCAGTACAACAGCACGTACCGTGTGGTCAGCGTCCTCACCGTCCTGCA
CCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTCTCCAACAAAGCCCT
CCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAACC
ACAGGTGTACACCCTGCCCCCATCCCGGGAGGAGATGACCAAGAACCAGGTCAG
CCTGACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGTGGAGTGGGAG
AGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCC
GACGGCTCCTTCTTCCTCTACAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGC
AGGGGAACGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCACTACAC
GCAGAAGAGCCTCTCCCTGTCTCCGGGTAAA
(SEQ ID NO: 87) [00276] DIQMTQ SP S SLSASVGDRVTITCRASQDIS SYLNWYQQKPGKAPKLLIYYT
SRLHSGVP SRFSGSGSGTDFTF TISSLQPEDIATYYCQQGNTLPYTF GQGTKVEIKRTV

AAP SVFIFPP SDEQLK SGTASVVCLLNNFYPREAKVQWKVDNALQ SGNSQESVTEQD
SKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
(SEQ ID NO: 88) [00277] GACATTCAGATGACCCAGAGCCCCAGCAGCCTGAGCGCCAGCGTGGG
AGACAGAGTGACCATCACCTGCAGAGCCAGCCAGGACATCTCCAGCTACCTGAA
CTGGTATCAGCAGAAACCCGGCAAAGCCCCAAAACTGCTGATCTACTACACCAG
TAGACTGCACAGCGGCGTGCCCAGCAGATTCTCAGGAAGCGGCTCCGGAACCGA
CTTCACCTTCACTATCAGCAGCCTGCAGCCCGAAGATATTGCTACTTACTACTGC
CAGCAGGGGAACACCCTGCCCTATACCTTCGGCCAGGGCACCAAGGTGGAGATC
AAACGTACGGTGGCTGCACCATCTGTCTTCATCTTCCCGCCATCTGATGAGCAGT
TGAAATCTGGAACTGCCTCTGTTGTGTGCCTGCTGAATAACTTCTATCCCAGAGA
GGCCAAAGTACAGTGGAAGGTGGATAACGCCCTCCAATCGGGTAACTCCCAGGA
GAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTCAGCAGCACCCT
GACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTACGCCTGCGAAGTCAC
CCATCAGGGCCTGAGTTCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGT
(SEQ ID NO: 89) [00278] SDTGRPFVEMYSEIPEIIHMTEGRELVIPCRVT SPNITVTLKKFPLDTLIPDG
KRIIWDSRKGFIISNATYKEIGLLTCEATVNGHLYKTNYLTHRQTNTIIDVVLSPSHGIE
LSVGEKLVLNCTARTELNVGIDFNWEYP S SKHQHKKLVNRDLKTQ SGSEMKKFLST
LTIDGVTRSDQGLYTCAASS GLMTKKNSTFVRVHEKGGSGGGSGGGGSGGGGGSGG
GGQVQLQESGPGLVRP SQTLSLTCTVSGYSITSDHAW SWVRQPPGRGLEWIGYISYS
GITTYNP SLKSRVTMLRDT SKNQF SLRLS SVTAADTAVYYCARSLARTTAMDYWGQ
GSLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGV
HTFPAVLQ S SGLYSL S SVVTVP S S SLGTQTYICNVNHKP SNTKVDKKVEPKSCDKTHT
CPPCPAPELLGGP SVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGV
EVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISK
AKGQPREPQVYTLPP SREEMTKNQ V SLTCL VKGF YP SDIAVEWESNGQPENNYKTTP
PVLD SDGSFFLYSKLTVDKSRWQQGNVF SC SVMHEALHNHYTQK SL SL SP G
(SEQ ID NO: 90) [00279] AGCGACACCGGCAGACCCTTCGTGGAGATGTACAGCGAGATCCCCGA
GATCATCCACATGACCGAGGGCAGAGAGCTGGTGATCCCCTGCAGAGTGACCAG
CCCCAACATCACCGTGACCCTGAAGAAGTTCCCCCTGGACACCCTGATCCCCGAC
GGCAAGAGAATCATCTGGGACAGCAGAAAGGGCTTCATCATCAGCAACGCCACC
TACAAGGAGATCGGCCTGCTGACCTGCGAGGCCACCGTGAACGGCCACCTGTAC
AAGACCAACTACCTGACCCACAGACAGACCAACACCATCATCGACGTGGTGCTG
AGCCCCAGCCACGGCATCGAGCTGAGCGTGGGCGAGAAGCTGGTGCTGAACTGC
ACCGCCAGAACCGAGCTGAACGTGGGCATCGACTTCAACTGGGAGTACCCCAGC
AGCAAGCACCAGCACAAGAAGCTGGTGAACAGAGACCTGAAGACCCAGAGCGG
CAGCGAGATGAAGAAGTTCCTGAGCACCCTGACCATCGACGGCGTGACCAGAAG
CGACCAGGGCCTGTACACCTGCGCCGCCAGCAGCGGCCTGATGACCAAGAAGAA
CAGCACCTTCGTGAGAGTGCACGAGAAGGGAGGAAGCGGAGGAGGAAGCGGGG
GAGGAGGAAGTGGAGGAGGAGGAGGGAGCGGAGGAGGGGGACAGGTGCAGCT
GCAGGAGAGCGGCCCCGGACTGGTGAGGCCTTCCCAGACCCTGAGCCTGACATG
CACAGTGAGCGGCTACAGCATCACAAGCGACCACGCCTGGAGCTGGGTGAGACA
GCCCCCCGGAAGAGGCCTGGAATGGATCGGATATATCTCCTACTCAGGCATTACC
ACCTACAACCCCTCTCTGAAAAGCAGAGTGACCATGCTGAGAGATACTAGCAAG
AACCAGTTTAGCCTGAGACTGTCTAGCGTGACTGCCGCCGACACCGCCGTGTACT
ACTGCGCCAGATCCCTGGCCCGGACCACAGCCATGGATTACTGGGGCCAGGGAA
GCCTGGTGACAGTGTCCTCCGCTAGCACCAAGGGCCCATCGGTCTTCCCCCTGGC
ACCCTCCTCCAAGAGCACCTCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAA
GGACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGCGCCCTGACCAG
CGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCAGGACTCTACTCCCTCAGC
AGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACCCAGACCTACATCTGCAACG
TGAATCACAAGCCCAGCAACACCAAGGTGGACAAGAAAGTTGAGCCCAAATCTT
GTGACAAAACTCACACATGCCCACCGTGCCCAGCACCTGAACTCCTGGGGGGAC
CGTCAGTCTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGAC
CCCCGAGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAA
GTTCAACTGGTACGTGGACGGCGTGGAGGTGCATAATGCCAAGACAAAGCCGCG
GGAGGAGCAGTACAACAGCACGTACCGTGTGGTCAGCGTCCTCACCGTCCTGCA
CCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTCTCCAACAAAGCCCT
CCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAACC
ACAGGTGTACACCCTGCCCCCATCCCGGGAGGAGATGACCAAGAACCAGGTCAG
CCTGACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGTGGAGTGGGAG

AGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCC
GACGGCTCCTTCTTCCTCTACAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGC
AGGGGAACGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCACTACAC
GCAGAAGAGCCTCTCCCTGTCTCCGGGT
(SEQ ID NO: 91) [00280] DIQMTQSPSSLSASVGDRVTITCRASQDISSYLNWYQQKPGKAPKLLIYYT
SRLHSGVPSRFSGSGSGTDFTFTISSLQPEDIATYYCQQGNTLPYTFGQGTKVEIKRTV
AAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQD
SKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
(SEQ ID NO: 92) [00281] GACATTCAGATGACCCAGAGCCCCAGCAGCCTGAGCGCCAGCGTGGG
AGACAGAGTGACCATCACCTGCAGAGCCAGCCAGGACATCTCCAGCTACCTGAA
CTGGTATCAGCAGAAACCCGGCAAAGCCCCAAAACTGCTGATCTACTACACCAG
TAGACTGCACAGCGGCGTGCCCAGCAGATTCTCAGGAAGCGGCTCCGGAACCGA
CTTCACCTTCACTATCAGCAGCCTGCAGCCCGAAGATATTGCTACTTACTACTGC
CAGCAGGGGAACACCCTGCCCTATACCTTCGGCCAGGGCACCAAGGTGGAGATC
AAACGTACGGTGGCTGCACCATCTGTCTTCATCTTCCCGCCATCTGATGAGCAGT
TGAAATCTGGAACTGCCTCTGTTGTGTGCCTGCTGAATAACTTCTATCCCAGAGA
GGCCAAAGTACAGTGGAAGGTGGATAACGCCCTCCAATCGGGTAACTCCCAGGA
GAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTCAGCAGCACCCT
GACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTACGCCTGCGAAGTCAC
CCATCAGGGCCTGAGTTCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGT
(SEQ ID NO: 93) [00282] QVQLQESGPGLVRP SQ TL SLT C TVS GYSIT SDHAW SWVRQPPGRGLEWIG
YISYSGITTYNPSLKSRVTMLRDTSKNQFSLRLSSVTAADTAVYYCARSLARTTAMD
YWGQGSLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGA
LTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSC
DKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWY
VDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIE
KTISKAKGQPREPQVYTLPP SREEMTKNQV S LT CLVKGF YP SD IAVEWE SNGQPENN

YKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVF SC SVMHEALHNHYTQKSLSLSP
(SEQ ID NO: 94) [00283] CAGGTGCAGCTGCAGGAGAGCGGCCCCGGACTGGTGAGGCCTTCCCA
GACCCTGAGCCTGACATGCACAGTGAGCGGCTACAGCATCACAAGCGACCACGC
CTGGAGCTGGGTGAGACAGCCCCCCGGAAGAGGCCTGGAATGGATCGGATATAT
CTCCTACTCAGGCATTACCACCTACAACCCCTCTCTGAAAAGCAGAGTGACCATG
CTGAGAGATACTAGCAAGAACCAGTTTAGCCTGAGACTGTCTAGCGTGACTGCC
GCCGACACCGCCGTGTACTACTGCGCCAGATCCCTGGCCCGGACCACAGCCATG
GATTACTGGGGCCAGGGAAGCCTGGTGACAGTGTCCTCCGCTAGCACCAAGGGC
CCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAGCACCTCTGGGGGCACAGCGG
CCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAACCGGTGACGGTGTCGTGGAA
CTCAGGCGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCA
GGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACCC
AGACCTACATCTGCAACGTGAATCACAAGCCCAGCAACACCAAGGTGGACAAGA
AAGTTGAGCCCAAATCTTGTGACAAAACTCACACATGCCCACCGTGCCCAGCACC
TGAACTCCTGGGGGGACCGTCAGTCTTCCTCTTCCCCCCAAAACCCAAGGACACC
CTCATGATCTCCCGGACCCCCGAGGTCACATGCGTGGTGGTGGACGTGAGCCACG
AAGACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGTGGAGGTGCATAATG
CCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGGTCAGCG
TCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCAAGG
TCTCCAACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAG
GGCAGCCCCGAGAACCACAGGTGTACACCCTGCCCCCATCCCGGGAGGAGATGA
CCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACAT
CGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGC
CTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTACAGCAAGCTCACCGTGGA
CAAGAGCAGGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGATGCATGAGGC
TCTGCACAACCACTACACGCAGAAGAGCCTCTCCCTGTCTCCG
(SEQ ID NO: 95) [00284] SDTGRPFVEMYSEIPEIIHMTEGRELVIPCRVT SPNITVTLKKFPLDTLIPDG
KRIIWD SRKGF II SNAT YKEIGLL TCEAT VNGHLYK TNYL THRQ TNTIID VVL SP SHGIE
L SVGEKLVLNCTARTELNVGIDFNWEYP S SKHQHKKLVNRDLKTQ SGSEMKKFLS T

LTIDGVTRSDQGLYTCAAS S GLMTKKNSTFVRVHEKDIQMTQ SP S SL SAS VGDRVTIT
CRASQDIS SYLNWYQQKPGKAPKLLIYYTSRLHSGVP SRF S GS GS GTDF TF TIS SLQPE
DIATYYCQQGNTLPYTFGQGTKVEIKRTVAAP SVFIFPP SDEQLKS GTASVVCLLNNF
YPREAKVQWKVDNALQ SGNSQESVTEQD SKD S TY SL S STLTLSKADYEKHKVYACE
VTHQGLS SPVTKSFNRGEC (SEQ ID NO: 96) [00285] AGCGACACCGGCAGACCCTTCGTGGAGATGTACAGCGAGATCCCCGA
GATCATCCACATGACCGAGGGCAGAGAGCTGGTGATCCCCTGCAGAGTGACCAG
CCCCAACATCACCGTGACCCTGAAGAAGTTCCCCCTGGACACCCTGATCCCCGAC
GGCAAGAGAATCATCTGGGACAGCAGAAAGGGCTTCATCATCAGCAACGCCACC
TACAAGGAGATCGGCCTGCTGACCTGCGAGGCCACCGTGAACGGCCACCTGTAC
AAGACCAACTACCTGACCCACAGACAGACCAACACCATCATCGACGTGGTGCTG
AGCCCCAGCCACGGCATCGAGCTGAGCGTGGGCGAGAAGCTGGTGCTGAACTGC
ACCGCCAGAACCGAGCTGAACGTGGGCATCGACTTCAACTGGGAGTACCCCAGC
AGCAAGCACCAGCACAAGAAGCTGGTGAACAGAGACCTGAAGACCCAGAGCGG
CAGCGAGATGAAGAAGTTCCTGAGCACCCTGACCATCGACGGCGTGACCAGAAG
CGACCAGGGCCTGTACACCTGCGCCGCCAGCAGCGGCCTGATGACCAAGAAGAA
CAGCACCTTCGTGAGAGTGCACGAGAAGGACATTCAGATGACCCAGAGCCCCAG
CAGCCTGAGCGCCAGCGTGGGAGACAGAGTGACCATCACCTGCAGAGCCAGCCA
GGACATCTCCAGCTACCTGAACTGGTATCAGCAGAAACCCGGCAAAGCCCCAAA
ACTGCTGATCTACTACACCAGTAGACTGCACAGCGGCGTGCCCAGCAGATTCTCA
GGAAGCGGCTCCGGAACCGACTTCACCTTCACTATCAGCAGCCTGCAGCCCGAA
GATATTGCTACTTACTACTGCCAGCAGGGGAACACCCTGCCCTATACCTTCGGCC
AGGGCACCAAGGTGGAGATCAAACGTACGGTGGCTGCACCATCTGTCTTCATCTT
CCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTGCTG
AATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTC
CAATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACC
TACAGCCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAA
GTCTACGCCTGCGAAGTCACCCATCAGGGCCTGAGTTCGCCCGTCACAAAGAGCT
TCAACAGGGGAGAGTGT
(SEQ ID NO: 97) [00286] QVQLQESGPGLVRP SQTLSLTCTVSGYSIT SDHAW SWVRQPPGRGLEWIG
YISYSGITTYNPSLKSRVTMLRDTSKNQFSLRLSSVTAADTAVYYCARSLARTTAMD

YWGQGSLVTVS SAS TKGP SVFPLAP S SK S T S GGTAALGCLVKDYFPEPVTVSWNS GA
LTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKP SNTKVDKKVEPKSC
DKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWY
VDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIE
KTISKAKGQPREPQVYTLPP SREEMTKNQVSLTCLVKGFYP SDIAVEWESNGQPENN
YKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVF SC SVMHEALHNHYTQKSLSLSP
(SEQ ID NO: 98) [00287] CAGGTGCAGCTGCAGGAGAGCGGCCCCGGACTGGTGAGGCCTTCCCA
GACCCTGAGCCTGACATGCACAGTGAGCGGCTACAGCATCACAAGCGACCACGC
CTGGAGCTGGGTGAGACAGCCCCCCGGAAGAGGCCTGGAATGGATCGGATATAT
CTCCTACTCAGGCATTACCACCTACAACCCCTCTCTGAAAAGCAGAGTGACCATG
CTGAGAGATACTAGCAAGAACCAGTTTAGCCTGAGACTGTCTAGCGTGACTGCC
GCCGACACCGCCGTGTACTACTGCGCCAGATCCCTGGCCCGGACCACAGCCATG
GATTACTGGGGCCAGGGAAGCCTGGTGACAGTGTCCTCCGCTAGCACCAAGGGC
CCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAGCACCTCTGGGGGCACAGCGG
CCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAACCGGTGACGGTGTCGTGGAA
CTCAGGCGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCA
GGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACCC
AGACCTACATCTGCAACGTGAATCACAAGCCCAGCAACACCAAGGTGGACAAGA
AAGTTGAGCCCAAATCTTGTGACAAAACTCACACATGCCCACCGTGCCCAGCACC
TGAACTCCTGGGGGGACCGTCAGTCTTCCTCTTCCCCCCAAAACCCAAGGACACC
CTCATGATCTCCCGGACCCCCGAGGTCACATGCGTGGTGGTGGACGTGAGCCACG
AAGACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGTGGAGGTGCATAATG
CCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGGTCAGCG
TCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCAAGG
TCTCCAACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAG
GGCAGCCCCGAGAACCACAGGTGTACACCCTGCCCCCATCCCGGGAGGAGATGA
CCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACAT
CGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGC
CTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTACAGCAAGCTCACCGTGGA
CAAGAGCAGGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGATGCATGAGGC
TCTGCACAACCACTACACGCAGAAGAGCCTCTCCCTGTCTCCG

(SEQ ID NO: 99) [00288] SDTGRPFVEMYSEIPEIIHMTEGRELVIPCRVT SPNITVTLKKFPLDTLIPDG
KRIIWD SRKGF II SNATYKEIGLLTCEATVNGHLYKTNYLTHRQ TNTIID VVL SP SHGIE
L SVGEKLVLNCTARTELNVGIDFNWEYP S SKHQHKKLVNRDLKTQ SGSEMKKFLS T
LTIDGVTRSDQGLYTCAASSGLMTKKNSTFVRVHEKGGSGGGSGGGGSGGGGGSGG
GGDIQMTQ SP S SL SA S VGDRVT ITCRA S QDIS SYLNWYQQKPGKAPKLLIYYT SRLHS
GVP SRF S GS GS GTDF TFTIS SLQPEDIATYYCQQGNTLPYTFGQGTKVEIKRTVAAP S V
FIFPP SDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQ SGNSQESVTEQD SKD ST
YSL S STLTLSKADYEKHKVYACEVTHQGL S SPVTKSFNRGEC
(SEQ ID NO: 100) [00289] AGCGACACCGGCAGACCCTTCGTGGAGATGTACAGCGAGATCCCCGA
GATCATCCACATGACCGAGGGCAGAGAGCTGGTGATCCCCTGCAGAGTGACCAG
CCCCAACATCACCGTGACCCTGAAGAAGTTCCCCCTGGACACCCTGATCCCCGAC
GGCAAGAGAATCATCTGGGACAGCAGAAAGGGCTTCATCATCAGCAACGCCACC
TACAAGGAGATCGGCCTGCTGACCTGCGAGGCCACCGTGAACGGCCACCTGTAC
AAGACCAACTACCTGACCCACAGACAGACCAACACCATCATCGACGTGGTGCTG
AGCCCCAGCCACGGCATCGAGCTGAGCGTGGGCGAGAAGCTGGTGCTGAACTGC
ACCGCCAGAACCGAGCTGAACGTGGGCATCGACTTCAACTGGGAGTACCCCAGC
AGCAAGCACCAGCACAAGAAGCTGGTGAACAGAGACCTGAAGACCCAGAGCGG
CAGCGAGATGAAGAAGTTCCTGAGCACCCTGACCATCGACGGCGTGACCAGAAG
CGACCAGGGCCTGTACACCTGCGCCGCCAGCAGCGGCCTGATGACCAAGAAGAA
CAGCACCTTCGTGAGAGTGCACGAGAAGGGAGGAAGCGGAGGAGGAAGCGGGG
GAGGAGGAAGTGGAGGAGGAGGAGGGAGCGGAGGAGGGGGAGACATTCAGAT
GACCCAGAGCCCCAGCAGCCTGAGCGCCAGCGTGGGAGACAGAGTGACCATCAC
CTGCAGAGCCAGCCAGGACATCTCCAGCTACCTGAACTGGTATCAGCAGAAACC
CGGCAAAGCCCCAAAACTGCTGATCTACTACACCAGTAGACTGCACAGCGGCGT
GCCCAGCAGATTCTCAGGAAGCGGCTCCGGAACCGACTTCACCTTCACTATCAGC
AGC C TGC AGC C C GAAGATATT GC TAC TTAC TAC TGC CAGC AGGGGAACAC C C T GC
CCTATACCTTCGGCCAGGGCACCAAGGTGGAGATCAAACGTACGGTGGCTGCAC
CATCTGTCTTCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCT
GTTGTGTGCCTGCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAG
GTGGATAACGCCCTCCAATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGAC

AGCAAGGACAGCACCTACAGCCTCAGCAGCACCC TGAC GC T GAGCAAAGCAGAC
TACGAGAAACACAAAGTCTACGCCTGCGAAGTCACCCATCAGGGCCTGAGTTCG
CCCGTCACAAAGAGCTTCAACAGGGGAGAGTGT (SEQ ID NO: 101) [00290] YSMTPPTLNITEESHVIDTGD SL S I S CRGQHPLEWAWP GAQEAPATGDKD
SED T GVVRD CEGTDARP YCKVLLLHEVHAND T GS YVCYYKYIKARIEGT TAA S SYV
FVRDFEQPFINKPDTLLVNRKDAMWVPCLVSIPGLNVTLRSQSSVLWPDGQEVVWD
DRRGMLV S TPLLHDALYLQ CET TWGD QDFL SNPFLVHITGNELYDIQLLPRK SLELL
VGEKLVLNC TVWAEFNSGVTFDWDYPGKQAERGKWVPERRSQQTHTELS SILTIHN
VSQHDLGSYVCKANNGIQRFRESTEVIVHEN (SEQ
ID NO: 102) [00291] TACAGCATGACCCCTCCTACCCTGAACATCACCGAGGAGAGCCACGT
GATCGACACCGGCGACAGCCTGAGCATCAGCTGCAGAGGCCAGCATCCTTTAGA
GTGGGC C T GGC C C GGC GC C CAGGAGGC T C C TGC CAC C GGC GAC AAGGACAGC GA
GGACAC C GGC GTGGTGAGAGAC T GC GAGGGCAC C GAC GC CAGAC C C TAC TGCAA
GGTGCTGCTGCTGCACGAGGTGCACGCCAACGACACCGGCAGCTACGTGTGCTA
C TACAAGTACAT CAAGGC CAGAATC GAGGGCAC CAC C GC C GC C AGCAGC TAC GT
GTTCGTGAGAGACTTCGAGCAGCCCTTCATCAACAAGCCCGACACCCTGCTGGTG
AACAGAAAGGACGCCATGTGGGTGCCCTGCCTGGTGAGCATCCCCGGCCTGAAC
GTGACCC TGAGAAGCCAGAGCAGCGTGCTGTGGCCCGACGGCCAGGAGGTGGTG
TGGGAC GACAGAAGAGGCAT GC T GGT GAGC AC T C C TC TGC TGCAC GAC GC CCTG
TACCTGCAGTGCGAGACCACCTGGGGCGACCAGGACTTCCTGAGCAACCCCTTCC
TGGTGCACATCACCGGCAACGAGCTGTACGACATCCAGCTGCTGCCCAGGAAGA
GC C TGGAGC TGC TGGTGGGCGAGAAGCTGGTGCTGAACTGCACCGTGTGGGCCG
AGTTCAAC TCCGGCGTGACC TT TGAC TGGGAC TAC C CC GGCAAGCAGGC C GAAA
GGGGAAAAT GGGT GC C C GAAAGAAGAAGT CAGC AGAC C CAC ACAGAAC TGAGC
TCCATCCTGACAATCCACAACGTGAGCCAGCACGACCTGGGCAGCTATGTGTGCA
AAGCTAACAACGGCATCCAGAGATTCAGAGAGAGCACCGAGGTGATCGTGCACG
AAAAT (SEQ ID NO: 103) SEQUENCE LISTING
<110> Eluminex Biosciences (Suzhou) Ltd <120> Antibody Fusion Proteins Targeting IL-6 Receptor and Angiogenic Factors <130> EB-002 <160> 103 <170> PatentIn version 3.5 <210> 1 <211> 1344 <212> DNA
<213> Homo sapiens <400> 1 caggtgcagc tgcaggaatc agggcctggt ttggtgcggc cgagtcagac gctcagcttg 60 acttgtacgg tgtcaggtta ctctatcact agcgatcatg cctggagctg ggtacgacaa 120 ccaccgggtc ggggtctcga atggataggt tacataagct actcaggaat cacgacatac 180 aatccctccc ttaaaagtcg ggtcaccatg ctccgagaca ctagtaaaaa tcagttctcc 240 ctgcggttgt ccagcgtgac tgctgccgac acggcggtct attattgcgc aagaagtctg 300 gcgcggacaa cggcaatgga ctactgggga caaggttcac tggtaaccgt tagttcagca 360 agcaccaagg gtccgtctgt ctttccactc gcgccttcta gcaagtcaac ctcagggggg 420 actgccgcgc ttggatgtct ggtcaaagat tattttcctg agccggtaac agttagctgg 480 aattcaggtg ccctcacatc tggggtacac acgtttcccg ccgtgcttca gagctctggc 540 ctctacagtc tttctagcgt ggtcaccgtc ccatcttcat cattgggtac acaaacttac 600 atttgtaacg ttaatcacaa acctagcaac actaaggtgg ataaaaaagt agagccaaag 660 tcctgcgaca agactcacac ctgtcctccc tgtccagcac ccgaactttt gggcggtcct 720 tctgttttcc tgtttcctcc taaacccaaa gatacactca tgatctccag aaccccggaa 780 gtaacctgcg tagtcgtgga cgtatcccat gaggatcccg aggtaaaatt caactggtac 840 gtagacgggg tcgaggtgca caatgccaag actaaaccta gggaagagca atacaatagt 900 acgtacaggg tggtttccgt gctgaccgtc ctgcatcagg attggctcaa cgggaaagag 960 tataaatgta aggtgtcaaa caaagctttg ccggcaccaa tagagaaaac cattagtaag 1020 gcgaaaggac aaccccgaga gccacaagtg tatacgttgc ctcccagccg cgaggaaatg 1080 acgaagaatc aagtctctct gacttgtctg gtgaagggtt tttacccgtc tgatatagct 1140 gtcgaatggg agtctaacgg ccagccagag aataattaca aaaccactcc tccggtcttg 1200 gattctgatg ggagcttttt cctgtattcc aaattgacag ttgataaaag tcggtggcag 1260 caggggaacg tcttctcctg tagcgtcatg catgaagcac tgcataatca ttatacccaa 1320 aaaagtttgt ccttgagccc tggt 1344 <210> 2 <211> 448 <212> PRT
<213> Homo sapiens <400> 2 Gin Val Gin Leu Gin Glu Ser Gly Pro Gly Leu Val Arg Pro Ser Gin Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Tyr Ser Ile Thr Ser Asp His Ala Trp Ser Trp Val Arg Gin Pro Pro Gly Arg Gly Leu Glu Trp Ile Gly Tyr Ile Ser Tyr Ser Gly Ile Thr Thr Tyr Asn Pro Ser Leu Lys Ser Arg Val Thr Met Leu Arg Asp Thr Ser Lys Asn Gin Phe Ser Leu Arg Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys Ala Arg Ser Leu Ala Arg Thr Thr Ala Met Asp Tyr Trp Gly Gin Gly Ser Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gin Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gin Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gin Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gin Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gin Pro Arg Glu Pro Gin Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gin Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gin Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gin Gin Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gin Lys Ser Leu Ser Leu Ser Pro Gly <210> 3 <211> 642 <212> DNA
<213> Homo sapiens <400> 3 gacattcaaa tgactcagtc tccatccagt ctctccgctt ctgtggggga ccgagtaacc 60 ataacatgtc gggcatctca ggacataagc tcatacttga attggtatca gcagaaacca 120 gggaaggcgc ccaagcttct tatctactat acatcaagac ttcatagcgg ggtgccaagc 180 cgattcagtg gcagcggttc aggaacagac tttacgttca ccatttcatc tttgcagcca 240 gaagatatag ctacgtacta ctgtcagcaa ggaaatacgt tgccgtacac ctttggccag 300 ggcacaaaag tcgaaattaa gcgaaccgta gcagccccga gtgtctttat ctttcctccc 360 tcagatgagc aacttaaaag cgggacagcc tcagtagttt gcctcctgaa caatttctac 420 ccacgggaag ccaaggtgca gtggaaggtg gacaatgctc ttcagtccgg caactctcag 480 gaaagtgtta ccgagcaaga ctctaaagac tcaacttaca gcctcagctc caccctcact 540 ttgtccaagg ctgattacga aaaacataag gtatatgcct gcgaagttac gcaccaagga 600 ctttcatccc cggtgacaaa gagcttcaac agaggcgaat gt 642 <210> 4 <211> 214 <212> PRT
<213> Homo sapiens <400> 4 Asp Ile Gin Met Thr Gin Ser Pro Ser Ser Leu Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gin Asp Ile Ser Ser Tyr Leu Asn Trp Tyr Gin Gin Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile Tyr Tyr Thr Ser Arg Leu His Ser Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Phe Thr Ile Ser Ser Leu Gin Pro Glu Asp Ile Ala Thr Tyr Tyr Cys Gin Gin Gly Asn Thr Leu Pro Tyr Thr Phe Gly Gin Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gin Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gin Trp Lys Val Asp Asn Ala Leu Gin Ser Gly Asn Ser Gin Glu Ser Val Thr Glu Gin Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gin Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys <210> 5 <211> 306 <212> DNA
<213> Homo sapiens <400> 5 tccgacacag gacgcccctt cgtagaaatg tactctgaga ttccggaaat catccatatg 60 actgagggca gagagttggt cataccatgc agagtcactt caccaaatat aaccgtgacg 120 ttgaagaaat ttcccttgga cacgttgatt cccgatggta agcggattat atgggacagc 180 cgcaagggct ttataataag taatgcaaca tataaggaaa taggtctcct cacatgcgaa 240 gctacagtca acggccatct ctacaagaca aattatctta cccacaggca gacgaacaca 300 ataatt 306 <210> 6 <211> 102 <212> PRT
<213> Homo sapiens <400> 6 Ser Asp Thr Gly Arg Pro Phe Val Glu Met Tyr Ser Glu Ile Pro Glu Ile Ile His Met Thr Glu Gly Arg Glu Leu Val Ile Pro Cys Arg Val Thr Ser Pro Asn Ile Thr Val Thr Leu Lys Lys Phe Pro Leu Asp Thr Leu Ile Pro Asp Gly Lys Arg Ile Ile Trp Asp Ser Arg Lys Gly Phe Ile Ile Ser Asn Ala Thr Tyr Lys Glu Ile Gly Leu Leu Thr Cys Glu Ala Thr Val Asn Gly His Leu Tyr Lys Thr Asn Tyr Leu Thr His Arg Gin Thr Asn Thr Ile Ile <210> 7 <211> 309 <212> DNA
<213> Homo sapiens <400> 7 gacgtggttc tttcaccctc acacggtatt gagttgtcag tcggtgagaa gctggtcttg 60 aactgcacgg ccagaacgga attgaacgtc ggcattgatt ttaactggga atacccgtcc 120 tctaaacacc aacacaagaa gttggtcaac cgcgatctga agacccaatc cggaagtgaa 180 atgaagaaat tcttgtctac tttgaccatt gatggcgtca cgagatctga tcaagggctt 240 tacacctgcg ccgcgagctc tggtcttatg accaagaaga acagtacatt tgtgcgggta 300 catgaaaaa 309 <210> 8 <211> 103 <212> PRT
<213> Homo sapiens <400> 8 Asp Val Val Leu Ser Pro Ser His Gly Ile Glu Leu Ser Val Gly Glu Lys Leu Val Leu Asn Cys Thr Ala Arg Thr Glu Leu Asn Val Gly Ile Asp Phe Asn Trp Glu Tyr Pro Ser Ser Lys His Gin His Lys Lys Leu Val Asn Arg Asp Leu Lys Thr Gin Ser Gly Ser Glu Met Lys Lys Phe Leu Ser Thr Leu Thr Ile Asp Gly Val Thr Arg Ser Asp Gin Gly Leu Tyr Thr Cys Ala Ala Ser Ser Gly Leu Met Thr Lys Lys Asn Ser Thr Phe Val Arg Val His Glu Lys <210> 9 <211> 615 <212> DNA
<213> Homo sapiens <400> 9 tattctatga caccgccgac cttgaacata accgaggaat cacatgtaat agacacaggg 60 gactcacttt caatcagctg tcgaggccag caccccctgg aatgggcttg gccgggggca 120 caagaagcac ctgctactgg tgacaaggac agcgaagata cgggagtagt tagagactgt 180 gagggcacag acgctagacc ttactgcaag gtcctgcttt tgcatgaagt gcacgctaac 240 gacactggga gctatgtctg ctactacaag tatatcaaag cgcggataga gggaacgaca 300 gctgcgtcaa gttatgtgtt cgtcagagat tttgagcaac cgtttattaa taagcctgac 360 acgctgcttg taaatagaaa agacgccatg tgggtaccat gtctggtcag tatacctggt 420 ctcaatgtga ctcttcgctc tcaaagcagc gtgctgtggc cggacggcca ggaagtggtt 480 tgggatgaca ggcgggggat gcttgtttcc actccgcttc tccatgacgc cctctacctg 540 caatgtgaaa ccacgtgggg tgatcaagat ttcctgtcta atcccttctt ggtacatatc 600 accgggaacg aactc 615 <210> 10 <211> 205 <212> PRT
<213> Homo sapiens <400> 10 Tyr Ser Met Thr Pro Pro Thr Leu Asn Ile Thr Glu Glu Ser His Val Ile Asp Thr Gly Asp Ser Leu Ser Ile Ser Cys Arg Gly Gin His Pro Leu Glu Trp Ala Trp Pro Gly Ala Gin Glu Ala Pro Ala Thr Gly Asp Lys Asp Ser Glu Asp Thr Gly Val Val Arg Asp Cys Glu Gly Thr Asp Ala Arg Pro Tyr Cys Lys Val Leu Leu Leu His Glu Val His Ala Asn Asp Thr Gly Ser Tyr Val Cys Tyr Tyr Lys Tyr Ile Lys Ala Arg Ile Glu Gly Thr Thr Ala Ala Ser Ser Tyr Val Phe Val Arg Asp Phe Glu Gin Pro Phe Ile Asn Lys Pro Asp Thr Leu Leu Val Asn Arg Lys Asp Ala Met Trp Val Pro Cys Leu Val Ser Ile Pro Gly Leu Asn Val Thr Leu Arg Ser Gin Ser Ser Val Leu Trp Pro Asp Gly Gin Glu Val Val Trp Asp Asp Arg Arg Gly Met Leu Val Ser Thr Pro Leu Leu His Asp Ala Leu Tyr Leu Gin Cys Glu Thr Thr Trp Gly Asp Gin Asp Phe Leu Ser Asn Pro Phe Leu Val His Ile Thr Gly Asn Glu Leu <210> 11 <211> 48 <212> DNA
<213> Artificial <220>
<223> Artificial linker <400> 11 ggagaaggtt ccggtgatgg aggtgagggg agcggggatg gggaaggt 48 <210> 12 <211> 16 <212> PRT
<213> Artificial <220>
<223> Artificial linker <400> 12 Gly Glu Gly Ser Gly Asp Gly Gly Glu Gly Ser Gly Asp Gly Glu Gly <210> 13 <211> 33 <212> DNA
<213> Artificial <220>
<223> Artificial linker <400> 13 ggaggctcag gtggcggtgg ttctggcgga gga 33 <210> 14 <211> 11 <212> PRT
<213> Artificial <220>
<223> Artificial linker <400> 14 Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly <210> 15 <211> 48 <212> DNA
<213> Artificial <220>
<223> Artificial sequence <400> 15 atgccgttgc tgctgctttt gccactcctt tgggccgggg ctttggca 48 <210> 16 <211> 16 <212> PRT
<213> Artificial <220>
<223> Artificial sequence <400> 16 Met Pro Leu Leu Leu Leu Leu Pro Leu Leu Trp Ala Gly Ala Leu Ala <210> 17 <211> 2058 <212> DNA
<213> Artificial <220>
<223> Artificial sequence <400> 17 atgcctctcc tcctcctctt gcccctcctt tgggccggag ccctggctca ggtgcagctg 60 caggaatcag ggcctggttt ggtgcggccg agtcagacgc tcagcttgac ttgtacggtg 120 tcaggttact ctatcactag cgatcatgcc tggagctggg tacgacaacc accgggtcgg 180 ggtctcgaat ggataggtta cataagctac tcaggaatca cgacatacaa tccctccctt 240 aaaagtcggg tcaccatgct ccgagacact agtaaaaatc agttctccct gcggttgtcc 300 agcgtgactg ctgccgacac ggcggtctat tattgcgcaa gaagtctggc gcggacaacg 360 gcaatggact actggggaca aggttcactg gtaaccgtta gttcagcaag caccaagggt 420 ccgtctgtct ttccactcgc gccttctagc aagtcaacct caggggggac tgccgcgctt 480 ggatgtctgg tcaaagatta ttttcctgag ccggtaacag ttagctggaa ttcaggtgcc 540 ctcacatctg gggtacacac gtttcccgcc gtgcttcaga gctctggcct ctacagtctt 600 tctagcgtgg tcaccgtccc atcttcatca ttgggtacac aaacttacat ttgtaacgtt 660 aatcacaaac ctagcaacac taaggtggat aaaaaagtag agccaaagtc ctgcgacaag 720 actcacacct gtcctccctg tccagcaccc gaacttttgg gcggtccttc tgttttcctg 780 tttcctccta aacccaaaga tacactcatg atctccagaa ccccggaagt aacctgcgta 840 gtcgtggacg tatcccatga ggatcccgag gtaaaattca actggtacgt agacggggtc 900 gaggtgcaca atgccaagac taaacctagg gaagagcaat acaatagtac gtacagggtg 960 gtttccgtgc tgaccgtcct gcatcaggat tggctcaacg ggaaagagta taaatgtaag 1020 gtgtcaaaca aagctttgcc ggcaccaata gagaaaacca ttagtaaggc gaaaggacaa 1080 ccccgagagc cacaagtgta tacgttgcct cccagccgcg aggaaatgac gaagaatcaa 1140 gtctctctga cttgtctggt gaagggtttt tacccgtctg atatagctgt cgaatgggag 1200 tctaacggcc agccagagaa taattacaaa accactcctc cggtcttgga ttctgatggg 1260 agctttttcc tgtattccaa attgacagtt gataaaagtc ggtggcagca ggggaacgtc 1320 ttctcctgta gcgtcatgca tgaagcactg cataatcatt atacccaaaa aagtttgtcc 1380 ttgagccctg gtggcgaggg ttcaggggat ggaggcgagg ggtccgggga cggcgaaggc 1440 tcagataccg gaagaccatt tgtggagatg tattccgaaa taccggagat aatacatatg 1500 acggaaggtc gagaactcgt catcccatgt cgcgtaacct ctccaaatat caccgtaaca 1560 ctcaaaaaat tccctcttga cacgttgata ccggacggca aaagaataat atgggattca 1620 aggaaaggat ttataataag caacgccaca tacaaagaga ttgggctgct cacttgtgaa 1680 gccactgtta atgggcactt gtataagact aattatctca cccaccgcca gacgaatact 1740 ataatagatg tcgttctgag cccaagtcat gggattgaac tttctgttgg cgaaaagctc 1800 gtgttgaatt gcactgctag gacggagctg aatgttggta tagatttcaa ttgggaatat 1860 cctagctcta aacaccagca caaaaaactc gttaatcgcg acttgaagac gcagtcagga 1920 tcagagatga aaaagttcct ctcaacgctg actatagatg gagtaacgag atccgaccag 1980 ggattgtaca cctgcgccgc gtcttccggg ctcatgacaa aaaaaaacag cactttcgta 2040 cgcgtccatg aaaaatag 2058 <210> 18 <211> 685 <212> PRT
<213> Artificial <220>
<223> Artificial sequence <400> 18 Met Pro Leu Leu Leu Leu Leu Pro Leu Leu Trp Ala Gly Ala Leu Ala Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Arg Pro Ser Gln Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Tyr Ser Ile Thr Ser Asp His Ala Trp Ser Trp Val Arg Gln Pro Pro Gly Arg Gly Leu Glu Trp Ile Gly Tyr Ile Ser Tyr Ser Gly Ile Thr Thr Tyr Asn Pro Ser Leu Lys Ser Arg Val Thr Met Leu Arg Asp Thr Ser Lys Asn Gin Phe Ser Leu Arg Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys Ala Arg Ser Leu Ala Arg Thr Thr Ala Met Asp Tyr Trp Gly Gin Gly Ser Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gin Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gin Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Gly Glu Gly Ser Gly Asp Gly Gly Glu Gly Ser Gly Asp Gly Glu Gly Ser Asp Thr Gly Arg Pro Phe Val Glu Met Tyr Ser Glu Ile Pro Glu Ile Ile His Met Thr Glu Gly Arg Glu Leu Val Ile Pro Cys Arg Val Thr Ser Pro Asn Ile Thr Val Thr Leu Lys Lys Phe Pro Leu Asp Thr Leu Ile Pro Asp Gly Lys Arg Ile Ile Trp Asp Ser Arg Lys Gly Phe Ile Ile Ser Asn Ala Thr Tyr Lys Glu Ile Gly Leu Leu Thr Cys Glu Ala Thr Val Asn Gly His Leu Tyr Lys Thr Asn Tyr Leu Thr His Arg Gin Thr Asn Thr Ile Ile Asp Val Val Leu Ser Pro Ser His Gly Ile Glu Leu Ser Val Gly Glu Lys Leu Val Leu Asn Cys Thr Ala Arg Thr Glu Leu Asn Val Gly Ile Asp Phe Asn Trp Glu Tyr Pro Ser Ser Lys His Gin His Lys Lys Leu Val Asn Arg Asp Leu Lys Thr Gin Ser Gly Ser Glu Met Lys Lys Phe Leu Ser Thr Leu Thr Ile Asp Gly Val Thr Arg Ser Asp Gin Gly Leu Tyr Thr Cys Ala Ala Ser Ser Gly Leu Met Thr Lys Lys Asn Ser Thr Phe Val Arg Val His Glu Lys <210> 19 <211> 1356 <212> DNA

<213> Artificial <220>
<223> Artificial sequence <400> 19 atgcccttgc tgctgttgct gccccttctc tgggcagggg cgctggctga cattcaaatg 60 actcagtctc catccagtct ctccgcttct gtgggggacc gagtaaccat aacatgtcgg 120 gcatctcagg acataagctc atacttgaat tggtatcagc agaaaccagg gaaggcgccc 180 aagcttctta tctactatac atcaagactt catagcgggg tgccaagccg attcagtggc 240 agcggttcag gaacagactt tacgttcacc atttcatctt tgcagccaga agatatagct 300 acgtactact gtcagcaagg aaatacgttg ccgtacacct ttggccaggg cacaaaagtc 360 gaaattaagc gaaccgtagc agccccgagt gtctttatct ttcctccctc agatgagcaa 420 cttaaaagcg ggacagcctc agtagtttgc ctcctgaaca atttctaccc acgggaagcc 480 aaggtgcagt ggaaggtgga caatgctctt cagtccggca actctcagga aagtgttacc 540 gagcaagact ctaaagactc aacttacagc ctcagctcca ccctcacttt gtccaaggct 600 gattacgaaa aacataaggt atatgcctgc gaagttacgc accaaggact ttcatccccg 660 gtgacaaaga gcttcaacag aggcgaatgt ggagaggggt ccggcgacgg cggtgaaggg 720 tctggtgatg gggaaggttc cgataccggt cgacccttcg tcgagatgta ttctgagatt 780 ccggaaatca tccacatgac cgaaggacga gagcttgtaa ttccttgccg agttacatca 840 cccaacataa cggtgacact caagaagttt cctttggata cattgattcc ggacgggaag 900 cgcataattt gggatagtag aaagggtttt attatcagca acgctacgta taaggagata 960 ggtctgctca cttgtgaagc cactgtgaat gggcacctgt acaaaacaaa ttatctcacc 1020 caccgacaga ctaacaccat tatcgatgtt gttttgtctc catctcatgg aatcgaactt 1080 agtgtcggag aaaagctcgt actgaattgc acagcccgaa cggaacttaa tgttgggatt 1140 gactttaatt gggagtatcc gtcttctaag catcaacaca agaagcttgt taacagggat 1200 ctcaagacgc aatccggatc agaaatgaaa aaatttctct ccactcttac tatagatgga 1260 gtcacacgct ccgaccaagg tctctacacg tgcgcagcta gtagtggtct gatgaccaaa 1320 aagaactcta cgttcgtgag agtacatgag aagtag 1356 <210> 20 <211> 451 <212> PRT
<213> Artificial <220>
<223> Artificial sequence <400> 20 Met Pro Leu Leu Leu Leu Leu Pro Leu Leu Trp Ala Gly Ala Leu Ala Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Asp Ile Ser Ser Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile Tyr Tyr Thr Ser Arg Leu His Ser Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Phe Thr Ile Ser Ser Leu Gln Pro Glu Asp Ile Ala Thr Tyr Tyr Cys Gln Gln Gly Asn Thr Leu Pro Tyr Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys Gly Glu Gly Ser Gly Asp Gly Gly Glu Gly Ser Gly Asp Gly Glu Gly Ser Asp Thr Gly Arg Pro Phe Val Glu Met Tyr Ser Glu Ile Pro Glu Ile Ile His Met Thr Glu Gly Arg Glu Leu Val Ile Pro Cys Arg Val Thr Ser Pro Asn Ile Thr Val Thr Leu Lys Lys Phe Pro Leu Asp Thr Leu Ile Pro Asp Gly Lys Arg Ile Ile Trp Asp Ser Arg Lys Gly Phe Ile Ile Ser Asn Ala Thr Tyr Lys Glu Ile Gly Leu Leu Thr Cys Glu Ala Thr Val Asn Gly His Leu Tyr Lys Thr Asn Tyr Leu Thr His Arg Gln Thr Asn Thr Ile Ile Asp Val Val Leu Ser Pro Ser His Gly Ile Glu Leu Ser Val Gly Glu Lys Leu Val Leu Asn Cys Thr Ala Arg Thr Glu Leu Asn Val Gly Ile Asp Phe Asn Trp Glu Tyr Pro Ser Ser Lys His Gln His Lys Lys Leu Val Asn Arg Asp Leu Lys Thr Gin Ser Gly Ser Glu Met Lys Lys Phe Leu Ser Thr Leu Thr Ile Asp Gly Val Thr Arg Ser Asp Gin Gly Leu Tyr Thr Cys Ala Ala Ser Ser Gly Leu Met Thr Lys Lys Asn Ser Thr Phe Val Arg Val His Glu Lys <210> 21 <211> 2043 <212> DNA
<213> Artificial <220>
<223> Artificial sequence <400> 21 atgcccctgc ttctcctctt gccgttgctc tgggctggtg ctttggcgca agtacaactt 60 caagaatcag gtcccgggct cgtgcggcct tcacaaacac ttagcctcac ctgcactgtg 120 tccgggtata gcataacaag tgaccacgcg tggagctggg tgcggcagcc tcctggtcgc 180 ggcctcgagt ggattggata catatcctac tcaggaatca ctacatataa tccaagtttg 240 aaatcccgag ttaccatgtt gagggacacg agtaaaaatc agttcagtct gaggttgtca 300 agcgtaacgg cggctgatac ggctgtttat tactgtgcaa gaagtttggc acgaacaacc 360 gcgatggact actggggtca aggctcattg gtaactgtga gctctgcgtc taccaagggc 420 cctagcgttt ttcctctggc cccttcctcc aagtccacgt ccggtggaac agctgctctc 480 ggctgtttgg taaaagatta tttcccagaa cccgttactg tgtcatggaa ctctggtgct 540 ttgacaagtg gagtccatac ttttcctgcc gttctgcaat caagtgggct ctatagcttg 600 tcctcagttg tcacagtacc atcatcaagc ctgggtacac agacttatat atgcaatgtg 660 aaccacaagc cttccaatac gaaagtcgac aagaaggtcg agcccaagtc atgcgacaag 720 acccatacct gccccccatg tccagccccc gaactgctgg gcggaccctc agtcttcctc 780 tttccaccaa agccgaaaga tacccttatg atctctagga cccccgaggt aacgtgcgtt 840 gtcgtcgatg tgtctcacga ggacccggag gtcaagttca attggtacgt cgatggcgtc 900 gaggttcata acgcgaagac taaaccgagg gaggaacaat acaactctac gtaccgagta 960 gtgtccgtgt tgacagtact gcatcaagat tggctcaatg gtaaagaata taaatgcaag 1020 gtctctaaca aagcgttgcc tgcgccaatc gaaaaaacta ttagcaaagc taagggtcaa 1080 ccgcgagagc ctcaggtata cacgcttcct ccgtcccgag aagagatgac gaaaaatcaa 1140 gtctccctga catgtcttgt taagggtttt tacccttctg acattgctgt cgaatgggag 1200 tccaatggcc agcccgagaa caactataag acgacgcctc ccgtcttgga tagtgacgga 1260 agctttttcc tgtattctaa attgaccgtg gacaagagcc ggtggcaaca gggtaacgtc 1320 ttttcatgct ccgtaatgca cgaggcgctt cataaccact acacccaaaa gagtctctca 1380 ttgtctcccg gtggcggttc aggtgggggg ggaagcggtg gtggatctga cactggacgg 1440 cctttcgttg agatgtactc agaaattccg gagatcattc acatgacaga agggagggag 1500 ttggtgatac cttgccgggt tacatcacca aacataactg taacactcaa aaaattcccc 1560 ctggatacac ttatccctga tggaaagcga ataatatggg acagtagaaa aggatttatc 1620 attagcaacg caacgtataa agaaatcgga ttgcttacct gcgaagcgac ggtgaatggc 1680 catctgtaca aaacgaacta cctcacgcac cgacaaacga acactatcat agatgtagtt 1740 ttgagtccta gtcacggtat tgagctcagc gtcggggaga aactggtcct taactgtact 1800 gctagaacgg aactcaacgt gggtatagat ttcaactggg agtacccgtc atccaaacat 1860 caacacaaga aacttgtcaa ccgagacctg aagacacaat ctggatcaga gatgaagaag 1920 tttttgtcta ctcttacaat tgatggggtc actcggtctg atcaaggact gtatacctgc 1980 gcagccagtt cagggttgat gactaaaaaa aattccacct tcgtacgagt ccacgagaag 2040 tag 2043 <210> 22 <211> 680 <212> PRT
<213> Artificial <220>
<223> Artificial sequence <400> 22 Met Pro Leu Leu Leu Leu Leu Pro Leu Leu Trp Ala Gly Ala Leu Ala Gin Val Gin Leu Gin Glu Ser Gly Pro Gly Leu Val Arg Pro Ser Gin Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Tyr Ser Ile Thr Ser Asp His Ala Trp Ser Trp Val Arg Gin Pro Pro Gly Arg Gly Leu Glu Trp Ile Gly Tyr Ile Ser Tyr Ser Gly Ile Thr Thr Tyr Asn Pro Ser Leu Lys Ser Arg Val Thr Met Leu Arg Asp Thr Ser Lys Asn Gin Phe Ser Leu Arg Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys Ala Arg Ser Leu Ala Arg Thr Thr Ala Met Asp Tyr Trp Gly Gin Gly Ser Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gin Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gin Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Ser Asp Thr Gly Arg Pro Phe Val Glu Met Tyr Ser Glu Ile Pro Glu Ile Ile His Met Thr Glu Gly Arg Glu Leu Val Ile Pro Cys Arg Val Thr Ser Pro Asn Ile Thr Val Thr Leu Lys Lys Phe Pro Leu Asp Thr Leu Ile Pro Asp Gly Lys Arg Ile Ile Trp Asp Ser Arg Lys Gly Phe Ile Ile Ser Asn Ala Thr Tyr Lys Glu Ile Gly Leu Leu Thr Cys Glu Ala Thr Val Asn Gly His Leu Tyr Lys Thr Asn Tyr Leu Thr His Arg Gln Thr Asn Thr Ile Ile Asp Val Val Leu Ser Pro Ser His Gly Ile Glu Leu Ser Val Gly Glu Lys Leu Val Leu Asn Cys Thr Ala Arg Thr Glu Leu Asn Val Gly Ile Asp Phe Asn Trp Glu Tyr Pro Ser Ser Lys His Gln His Lys Lys Leu Val Asn Arg Asp Leu Lys Thr Gln Ser Gly Ser Glu Met Lys Lys Phe Leu Ser Thr Leu Thr Ile Asp Gly Val Thr Arg Ser Asp Gln Gly Leu Tyr Thr Cys Ala Ala Ser Ser Gly Leu Met Thr Lys Lys Asn Ser Thr Phe Val Arg Val His Glu Lys <210> 23 <211> 1341 <212> DNA
<213> Artificial <220>
<223> Artificial sequence <400> 23 atgcctctgc tccttctcct gccattgttg tgggctggtg cgctcgcaga tattcaaatg 60 actcagtctc cttcaagcct ttccgcctca gtcggcgaca gagtaacaat aacttgtcgg 120 gcgtctcaag atatctcctc atatttgaat tggtaccagc aaaaacccgg taaagcacca 180 aagcttctca tctactatac ctcaagactg cattccgggg tgccgagccg gtttagcgga 240 tctggatctg gaacagactt tacattcacg atttccagcc tgcagccgga ggatattgcc 300 acctattatt gtcagcaggg aaacacgttg ccttacactt tcggacaggg aaccaaagtg 360 gagataaaga ggactgttgc cgcaccgagc gtgtttatct ttcctccttc agatgagcag 420 cttaagtctg gtacagcctc agttgtatgt ttgctgaaca acttctaccc aagggaagct 480 aaagtacagt ggaaggttga taatgccctt caatccggga actctcaaga gtctgtaaca 540 gaacaagata gtaaggactc aacgtatagc ctttccagca cgttgacgct gagtaaggca 600 gactatgaaa agcacaaggt ctacgcgtgc gaggtgacac accaaggcct gtcttcccct 660 gtaaccaaaa gctttaacag gggtgagtgc ggtggaagcg gcggcggcgg ttctggaggc 720 gggtcagaca ctggtcgacc gtttgtcgag atgtattctg agatacctga gattatccac 780 atgacagaag gacgggaact ggtgatccct tgccgggtaa cctcacccaa tatcaccgtg 840 acattgaaaa agtttcccct tgacacactt atacctgacg gaaagaggat catttgggac 900 agtcgcaagg gtttcatcat ttccaacgca acatataaag agataggact tttgacgtgc 960 gaagcgacgg tcaatggtca cttgtacaag acgaactatt tgacccatag acaaacgaac 1020 actataatag atgttgtgct tagtccaagt cacgggatag aattgagtgt aggcgagaag 1080 cttgtactca attgtacggc ccgaaccgag ctcaacgttg gaatagactt caactgggag 1140 taccctagca gcaagcacca acataagaag cttgtaaacc gcgatttgaa gacgcagtca 1200 ggcagtgaaa tgaaaaagtt cttgtccact ttgacgattg atggtgttac gagatcagac 1260 cagggcttgt atacctgcgc agcgtcaagc gggctgatga cgaagaagaa ctcaactttt 1320 gtcagagttc acgaaaagta g 1341 <210> 24 <211> 446 <212> PRT
<213> Artificial <220>
<223> Artificial sequence <400> 24 Met Pro Leu Leu Leu Leu Leu Pro Leu Leu Trp Ala Gly Ala Leu Ala Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Asp Ile Ser Ser Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile Tyr Tyr Thr Ser Arg Leu His Ser Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Phe Thr Ile Ser Ser Leu Gln Pro Glu Asp Ile Ala Thr Tyr Tyr Cys Gln Gln Gly Asn Thr Leu Pro Tyr Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Ser Asp Thr Gly Arg Pro Phe Val Glu Met Tyr Ser Glu Ile Pro Glu Ile Ile His Met Thr Glu Gly Arg Glu Leu Val Ile Pro Cys Arg Val Thr Ser Pro Asn Ile Thr Val Thr Leu Lys Lys Phe Pro Leu Asp Thr Leu Ile Pro Asp Gly Lys Arg Ile Ile Trp Asp Ser Arg Lys Gly Phe Ile Ile Ser Asn Ala Thr Tyr Lys Glu Ile Gly Leu Leu Thr Cys Glu Ala Thr Val Asn Gly His Leu Tyr Lys Thr Asn Tyr Leu Thr His Arg Gln Thr Asn Thr Ile Ile Asp Val Val Leu Ser Pro Ser His Gly Ile Glu Leu Ser Val Gly Glu Lys Leu Val Leu Asn Cys Thr Ala Arg Thr Glu Leu Asn Val Gly Ile Asp Phe Asn Trp Glu Tyr Pro Ser Ser Lys His Gin His Lys Lys Leu Val Asn Arg Asp Leu Lys Thr Gin Ser Gly Ser Glu Met Lys Lys Phe Leu Ser Thr Leu Thr Ile Asp Gly Val Thr Arg Ser Asp Gin Gly Leu Tyr Thr Cys Ala Ala Ser Ser Gly Leu Met Thr Lys Lys Asn Ser Thr Phe Val Arg Val His Glu Lys <210> 25 <211> 2043 <212> DNA
<213> Artificial <220>
<223> Artificial sequence <400> 25 atgccgcttc ttttgttgct ccccctgctg tgggcggggg ccctcgcgca agttcaactg 60 caggagagcg gcccgggttt ggtacgacca agccaaacac tctcacttac atgcaccgtg 120 tcagggtata gcattacctc agaccacgcg tggagctggg tacggcagcc gccgggtcga 180 ggcctcgagt ggatagggta tatctcttac tcaggtatta caacatacaa cccgtctctt 240 aagtctcgcg tgaccatgct gcgggataca agcaaaaacc agttctccct cagactgagc 300 tctgtcactg cggccgatac tgctgtctac tattgtgctc gaagtttggc gaggacaacg 360 gctatggact attggggcca aggatccctg gtaacagttt cttctgcaag tacgaaaggc 420 ccaagtgtgt ttccactggc tccctcctct aagagcactt ctgggggaac ggcagctctg 480 ggctgccttg tgaaggacta ctttcctgag ccagtaacag tctcctggaa ttcaggagcc 540 cttactagcg gtgttcatac gttcccggcc gttctgcaga gtagcgggct ttactctctg 600 tcatctgttg tgacggttcc atccagcagc ttgggcacac agacctacat atgcaatgtc 660 aatcacaaac cttctaatac aaaggtggat aaaaaagtcg agcctaagag ttgcgataag 720 acccatacct gtcctccatg tcccgcacca gaacttttgg gcgggccatc agtgtttctg 780 ttccccccca agcctaaaga tacccttatg attagtagaa cacccgaagt gacctgtgta 840 gtagtggatg ttagccatga ggaccctgaa gttaaattca attggtatgt cgatggggtt 900 gaagttcaca atgccaaaac taagccccgc gaagaacagt ataacagtac atatagggtc 960 gtttcagtac tgacagtatt gcaccaggac tggttgaacg gaaaggagta taagtgcaaa 1020 gtcagcaaca aagccctgcc tgcacctatc gaaaaaacca tcagtaaggc aaagggacag 1080 ccgagggaac cgcaggtgta cacgctcccc ccgtccagag aagagatgac aaagaaccag 1140 gtcagcctga catgtttggt caagggattc tatccgtcag acattgccgt cgagtgggag 1200 agtaatggcc agcccgagaa taattataaa actactccgc ccgtgcttga ctccgacggg 1260 tcatttttcc tctatagcaa actgaccgtg gataagtcaa gatggcaaca aggtaacgtc 1320 tttagttgta gtgttatgca tgaggcgctt cataaccact atacacagaa gagtttgagt 1380 ttgtcacctg gtggggggag cggtggtgga ggttctggtg gtggttatag catgactcca 1440 cccaccctga acatcactga agaatcacat gtcatcgaca ctggtgactc cttgtccata 1500 agttgccggg ggcaacaccc tctggaatgg gcctggcccg gtgcacagga ggccccagcg 1560 actggcgaca aggactcaga ggacacgggg gttgtcagag attgtgaggg gactgacgcg 1620 aggccgtatt gcaaagttct gctgcttcat gaagtgcacg caaacgatac gggatcttac 1680 gtgtgctact acaaatatat aaaggcccgg attgaaggta cgacagcggc ttcaagctac 1740 gtattcgtta gggatttcga gcaaccattc atcaacaagc ctgatacatt gttggttaac 1800 cgaaaagacg ccatgtgggt cccttgcctc gtctccattc cgggacttaa tgtaacactc 1860 aggagccaaa gttccgtctt gtggcccgac ggccaagaag tagtttggga cgacaggcga 1920 ggcatgctcg tgagtacgcc gctgcttcat gatgcgctgt accttcaatg cgagacgact 1980 tggggtgacc aagactttct ctctaaccct tttctggtcc atatcacagg gaacgagctc 2040 tag 2043 <210> 26 <211> 680 <212> PRT

<213> Artificial <220>
<223> Artificial sequence <400> 26 Met Pro Leu Leu Leu Leu Leu Pro Leu Leu Trp Ala Gly Ala Leu Ala Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Arg Pro Ser Gln Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Tyr Ser Ile Thr Ser Asp His Ala Trp Ser Trp Val Arg Gln Pro Pro Gly Arg Gly Leu Glu Trp Ile Gly Tyr Ile Ser Tyr Ser Gly Ile Thr Thr Tyr Asn Pro Ser Leu Lys Ser Arg Val Thr Met Leu Arg Asp Thr Ser Lys Asn Gln Phe Ser Leu Arg Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys Ala Arg Ser Leu Ala Arg Thr Thr Ala Met Asp Tyr Trp Gly Gln Gly Ser Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gin Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gin Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gin Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gin Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gin Pro Arg Glu Pro Gin Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gin Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gin Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gin Gin Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gin Lys Ser Leu Ser Leu Ser Pro Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Tyr Ser Met Thr Pro Pro Thr Leu Asn Ile Thr Glu Glu Ser His Val Ile Asp Thr Gly Asp Ser Leu Ser Ile Ser Cys Arg Gly Gin His Pro Leu Glu Trp Ala Trp Pro Gly Ala Gin Glu Ala Pro Ala Thr Gly Asp Lys Asp Ser Glu Asp Thr Gly Val Val Arg Asp Cys Glu Gly Thr Asp Ala Arg Pro Tyr Cys Lys Val Leu Leu Leu His Glu Val His Ala Asn Asp Thr Gly Ser Tyr Val Cys Tyr Tyr Lys Tyr Ile Lys Ala Arg Ile Glu Gly Thr Thr Ala Ala Ser Ser Tyr Val Phe Val Arg Asp Phe Glu Gin Pro Phe Ile Asn Lys Pro Asp Thr Leu Leu Val Asn Arg Lys Asp Ala Met Trp Val Pro Cys Leu Val Ser Ile Pro Gly Leu Asn Val Thr Leu Arg Ser Gin Ser Ser Val Leu Trp Pro Asp Gly Gin Glu Val Val Trp Asp Asp Arg Arg Gly Met Leu Val Ser Thr Pro Leu Leu His Asp Ala Leu Tyr Leu Gin Cys Glu Thr Thr Trp Gly Asp Gin Asp Phe Leu Ser Asn Pro Phe Leu Val His Ile Thr Gly Asn Glu Leu <210> 27 <211> 1356 <212> DNA
<213> Artificial <220>
<223> Artificial sequence <400> 27 atgcccttgc tcctgttgct ccccctgctc tgggcaggag ctcttgctga catacaaatg 60 actcaatctc ctagctcact ctccgctagt gtgggcgatc gggtaaccat cacatgtcgg 120 gccagccagg acatatcttc atatctgaat tggtatcagc agaagccagg gaaggcccct 180 aagctgctta tctactacac gtcaaggttg cactcaggtg tcccgtctcg gttctctggt 240 agtgggtccg ggactgactt tacattcaca attagtagcc tccagcccga ggacatagcg 300 acttactact gccaacaggg taataccttg ccctacactt tcggacaagg gaccaaggtt 360 gagattaagc gaacggtcgc tgctcccagt gtgttcattt ttcctccgtc tgatgaacag 420 ttgaaatccg ggaccgctag cgttgtgtgt ctcctgaata acttttaccc aagggaggcc 480 aaagttcaat ggaaagtaga taacgccttg cagagtggaa acagccagga gagtgttact 540 gagcaagact caaaagattc aacctatagc ctcagctcca ctctcacgct gagcaaagct 600 gactacgaaa agcacaaggt atatgcctgc gaagttactc atcaaggact gagctctcca 660 gtgacgaaga gtttcaaccg gggggaatgc ggcgaaggct ccggagacgg cggtgaggga 720 agcggcgatg gagaggggtc cgatactggc cgcccctttg tggagatgta ttctgagatc 780 ccggagatta tacacatgac tgagggacga gagctcgtta tcccatgtcg agtaacgagt 840 ccgaatataa cggtcacgct caaaaaattt cccttggata ccttgatacc agatggtaag 900 cgaataatct gggattctcg gaaagggttt attatctcaa acgctacgta caaagaaata 960 gggcttttga cttgtgaggc tacagttaat ggacatcttt ataaaacgaa ttatcttacg 1020 caccgacaga caaacaccat aatagatgtt gtcctttctc cctctcatgg aattgagttg 1080 agcgtgggtg aaaagttggt gctgaactgc accgctcgca ctgagcttaa tgtcggaatt 1140 gattttaatt gggagtaccc ttcaagcaaa catcagcata agaaactggt aaatagagat 1200 cttaaaacac agtcaggtag cgaaatgaaa aagttcctga gtacgttgac aatcgacggt 1260 gtgactagat ccgatcaagg tctctataca tgtgccgcca gttctggtct gatgaccaaa 1320 aagaatagta catttgttcg agttcacgag aaatag 1356 <210> 28 <211> 451 <212> PRT
<213> Artificial <220>
<223> Artificial sequence <400> 28 Met Pro Leu Leu Leu Leu Leu Pro Leu Leu Trp Ala Gly Ala Leu Ala Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Asp Ile Ser Ser Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile Tyr Tyr Thr Ser Arg Leu His Ser Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Phe Thr Ile Ser Ser Leu Gln Pro Glu Asp Ile Ala Thr Tyr Tyr Cys Gln Gln Gly Asn Thr Leu Pro Tyr Thr Phe Gly Gin Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gin Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gin Trp Lys Val Asp Asn Ala Leu Gin Ser Gly Asn Ser Gin Glu Ser Val Thr Glu Gin Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gin Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys Gly Glu Gly Ser Gly Asp Gly Gly Glu Gly Ser Gly Asp Gly Glu Gly Ser Asp Thr Gly Arg Pro Phe Val Glu Met Tyr Ser Glu Ile Pro Glu Ile Ile His Met Thr Glu Gly Arg Glu Leu Val Ile Pro Cys Arg Val Thr Ser Pro Asn Ile Thr Val Thr Leu Lys Lys Phe Pro Leu Asp Thr Leu Ile Pro Asp Gly Lys Arg Ile Ile Trp Asp Ser Arg Lys Gly Phe Ile Ile Ser Asn Ala Thr Tyr Lys Glu Ile Gly Leu Leu Thr Cys Glu Ala Thr Val Asn Gly His Leu Tyr Lys Thr Asn Tyr Leu Thr His Arg Gln Thr Asn Thr Ile Ile Asp Val Val Leu Ser Pro Ser His Gly Ile Glu Leu Ser Val Gly Glu Lys Leu Val Leu Asn Cys Thr Ala Arg Thr Glu Leu Asn Val Gly Ile Asp Phe Asn Trp Glu Tyr Pro Ser Ser Lys His Gln His Lys Lys Leu Val Asn Arg Asp Leu Lys Thr Gln Ser Gly Ser Glu Met Lys Lys Phe Leu Ser Thr Leu Thr Ile Asp Gly Val Thr Arg Ser Asp Gln Gly Leu Tyr Thr Cys Ala Ala Ser Ser Gly Leu Met Thr Lys Lys Asn Ser Thr Phe Val Arg Val His Glu Lys <210> 29 <211> 2043 <212> DNA
<213> Artificial <220>
<223> Artificial sequence <400> 29 atgcccctcc tccttttgct tcctctgctg tgggcgggcg cgctggcaca agtacaattg 60 caagagagcg gcccaggtct cgtaaggccg tcccagactt tgtctctgac atgcacagta 120 tcagggtatt ccatcactag tgatcacgct tggtcctggg tccgacagcc gcctgggaga 180 ggcctggagt ggatagggta catctcctac tccggaataa cgacgtacaa cccgagtctg 240 aagtctcgag taaccatgct gagggataca agcaagaatc agttttcatt gaggctctca 300 tccgttacag ccgccgacac agctgtctat tattgcgctc gcagtttggc cagaaccact 360 gcaatggatt actggggcca aggatccctg gttaccgtca gctcagctag cacgaaaggt 420 ccatctgttt tcccacttgc accgtccagt aagtccacct caggcggaac cgctgccctt 480 ggatgcctgg tcaaggatta tttccccgag ccagtcacag tcagctggaa ctctggagcc 540 ctcaccagcg gagttcacac gtttcccgct gtcttgcaaa gttccgggct ctacagtctg 600 agctctgtag taaccgtgcc cagttcaagc cttgggaccc aaacttacat atgtaatgta 660 aatcacaagc caagcaacac taaggtggat aaaaaagtcg agccgaaatc ctgcgacaaa 720 acacacacgt gtcctccgtg tccggctccc gaattgcttg gcggcccctc cgtgtttctg 780 ttcccaccga agccaaagga cactctgatg atctctcgca cgccagaagt gacatgcgtc 840 gttgtagacg tatcacacga agaccccgaa gttaagttta actggtatgt ggatggagtc 900 gaagtacata atgccaagac gaaaccaagg gaagaacaat acaattctac atatcgggtc 960 gtgagtgttc tgacggtatt gcatcaagat tggctcaacg gtaaagaata caaatgtaag 1020 gtgagtaata aagcgcttcc cgctccaata gagaagacaa tatccaaagc taaaggtcag 1080 ccacgggagc cgcaagttta taccttgccg ccttcaagag aagagatgac aaaaaaccag 1140 gtttccctta cgtgcctggt gaagggattt tacccaagtg atatagcagt tgaatgggag 1200 agcaacggtc aaccagaaaa caactacaag actactcccc cagttctcga ctctgatggg 1260 tctttctttt tgtactcaaa actcaccgtt gacaaatcaa gatggcagca aggcaacgtt 1320 ttttcatgta gcgtcatgca tgaggccttg cacaaccact acacgcaaaa aagcctcagt 1380 ttgagtcccg ggggtggtag tggcggtggc ggttccggcg gtgggtattc tatgacacca 1440 cccacgctca atattacaga ggagagccac gtaattgata caggtgattc tctgtccatt 1500 agttgcaggg gtcaacatcc gctggaatgg gcctggccgg gtgcgcaaga agcacccgca 1560 acaggagata aagactccga agatacgggg gtggtcagag attgtgaagg gacagatgca 1620 aggccttatt gtaaggtttt gcttctccac gaggtacatg cgaacgatac tgggtcttac 1680 gtgtgttact acaagtatat caaagctagg atcgagggga ctaccgccgc gagttcttat 1740 gtttttgtcc gagacttcga gcagccgttc atcaataaac ctgacacact gttggtaaac 1800 cggaaagacg ccatgtgggt gccttgtctt gtttctatcc cgggtctgaa cgtcactctt 1860 aggagtcagt ccagcgtcct ctggcccgat ggccaggagg tcgtctggga tgacagaagg 1920 ggcatgttgg tatccactcc gcttttgcac gatgcgctgt accttcagtg tgagaccact 1980 tggggtgacc aagattttct ctcaaatccc tttctggtcc acataaccgg caacgagctc 2040 tag 2043 <210> 30 <211> 680 <212> PRT
<213> Artificial <220>
<223> Artificial sequence <400> 30 Met Pro Leu Leu Leu Leu Leu Pro Leu Leu Trp Ala Gly Ala Leu Ala Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Arg Pro Ser Gln Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Tyr Ser Ile Thr Ser Asp His Ala Trp Ser Trp Val Arg Gln Pro Pro Gly Arg Gly Leu Glu Trp Ile Gly Tyr Ile Ser Tyr Ser Gly Ile Thr Thr Tyr Asn Pro Ser Leu Lys Ser Arg Val Thr Met Leu Arg Asp Thr Ser Lys Asn Gln Phe Ser Leu Arg Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys Ala Arg Ser Leu Ala Arg Thr Thr Ala Met Asp Tyr Trp Gly Gln Gly Ser Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gin Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gin Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gin Gin Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gin Lys Ser Leu Ser Leu Ser Pro Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Tyr Ser Met Thr Pro Pro Thr Leu Asn Ile Thr Glu Glu Ser His Val Ile Asp Thr Gly Asp Ser Leu Ser Ile Ser Cys Arg Gly Gin His Pro Leu Glu Trp Ala Trp Pro Gly Ala Gin Glu Ala Pro Ala Thr Gly Asp Lys Asp Ser Glu Asp Thr Gly Val Val Arg Asp Cys Glu Gly Thr Asp Ala Arg Pro Tyr Cys Lys Val Leu Leu Leu His Glu Val His Ala Asn Asp Thr Gly Ser Tyr Val Cys Tyr Tyr Lys Tyr Ile Lys Ala Arg Ile Glu Gly Thr Thr Ala Ala Ser Ser Tyr Val Phe Val Arg Asp Phe Glu Gln Pro Phe Ile Asn Lys Pro Asp Thr Leu Leu Val Asn Arg Lys Asp Ala Met Trp Val Pro Cys Leu Val Ser Ile Pro Gly Leu Asn Val Thr Leu Arg Ser Gln Ser Ser Val Leu Trp Pro Asp Gly Gln Glu Val Val Trp Asp Asp Arg Arg Gly Met Leu Val Ser Thr Pro Leu Leu His Asp Ala Leu Tyr Leu Gln Cys Glu Thr Thr Trp Gly Asp Gln Asp Phe Leu Ser Asn Pro Phe Leu Val His Ile Thr Gly Asn Glu Leu <210> 31 <211> 1341 <212> DNA
<213> Artificial <220>
<223> Artificial sequence <400> 31 atgccgctcc tgcttcttct cccactcctc tgggccggag cgcttgccga catacagatg 60 acccagtccc ctagtagcct cagcgcaagc gttggagatc gggtgactat aacgtgccga 120 gcgtcccaag acatttcttc ttatttgaat tggtatcaac aaaaaccagg gaaagccccg 180 aaactgctga tttattacac cagtcgactg cactccggag tccctagtcg gttcagcggg 240 tctggatcag gtactgattt tacctttact ataagctcac tccagccaga ggacattgcg 300 acctattatt gccagcaggg aaacacactt ccgtacacgt ttggccaggg gaccaaagtt 360 gaaatcaaga ggaccgtggc agccccctca gttttcatat tccctccgtc tgacgagcag 420 ttgaagtcag ggactgcatc cgtggtgtgt ctgctgaata atttctaccc acgcgaggcc 480 aaggtgcagt ggaaggtaga taatgctctc caatccggga acagccaaga gtctgttact 540 gaacaagatt ccaaagactc tacctatagc ctctcaagca cccttacact tagtaaggcg 600 gattacgaaa aacacaaagt ctacgcatgt gaagtgaccc atcagggtct cagcagcccg 660 gtcactaaaa gctttaacag gggggaatgt ggggggagtg gtggtggagg tagcggcggt 720 ggctccgaca ccggaaggcc tttcgtagag atgtattcag aaattcccga aattatacat 780 atgacggaag gcagagagct ggtcataccg tgtagagtaa catcacccaa cataactgtt 840 acgcttaaaa agttcccact tgacacactt atacccgacg gcaagagaat aatctgggac 900 agcagaaaag gtttcatcat ctccaatgct acttataaag agatcgggct cctgacgtgc 960 gaggcgaccg taaacgggca tttgtacaaa accaactatc tcactcatag acaaacaaac 1020 actattattg atgtggtgct cagcccctct catgggatcg agctttccgt aggtgaaaag 1080 ctggtcctga actgcacagc acggactgag ttgaatgtag ggatagattt caactgggaa 1140 tacccgtctt caaaacatca gcacaaaaag cttgtgaatc gcgacctcaa gacacaatca 1200 gggtcagaaa tgaaaaagtt tctctcaacg ctgactatcg acggcgtcac gcggtccgat 1260 cagggccttt acacttgtgc ggcctcttct gggttgatga cgaagaaaaa cagtacgttt 1320 gtacgcgtac atgagaagta g 1341 <210> 32 <211> 446 <212> PRT
<213> Artificial <220>
<223> Artificial sequence <400> 32 Met Pro Leu Leu Leu Leu Leu Pro Leu Leu Trp Ala Gly Ala Leu Ala Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Asp Ile Ser Ser Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile Tyr Tyr Thr Ser Arg Leu His Ser Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Phe Thr Ile Ser Ser Leu Gin Pro Glu Asp Ile Ala Thr Tyr Tyr Cys Gin Gin Gly Asn Thr Leu Pro Tyr Thr Phe Gly Gin Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gin Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gin Trp Lys Val Asp Asn Ala Leu Gin Ser Gly Asn Ser Gin Glu Ser Val Thr Glu Gin Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gin Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Ser Asp Thr Gly Arg Pro Phe Val Glu Met Tyr Ser Glu Ile Pro Glu Ile Ile His Met Thr Glu Gly Arg Glu Leu Val Ile Pro Cys Arg Val Thr Ser Pro Asn Ile Thr Val Thr Leu Lys Lys Phe Pro Leu Asp Thr Leu Ile Pro Asp Gly Lys Arg Ile Ile Trp Asp Ser Arg Lys Gly Phe Ile Ile Ser Asn Ala Thr Tyr Lys Glu Ile Gly Leu Leu Thr Cys Glu Ala Thr Val Asn Gly His Leu Tyr Lys Thr Asn Tyr Leu Thr His Arg Gin Thr Asn Thr Ile Ile Asp Val Val Leu Ser Pro Ser His Gly Ile Glu Leu Ser Val Gly Glu Lys Leu Val Leu Asn Cys Thr Ala Arg Thr Glu Leu Asn Val Gly Ile Asp Phe Asn Trp Glu Tyr Pro Ser Ser Lys His Gin His Lys Lys Leu Val Asn Arg Asp Leu Lys Thr Gin Ser Gly Ser Glu Met Lys Lys Phe Leu Ser Thr Leu Thr Ile Asp Gly Val Thr Arg Ser Asp Gin Gly Leu Tyr Thr Cys Ala Ala Ser Ser Gly Leu Met Thr Lys Lys Asn Ser Thr Phe Val Arg Val His Glu Lys <210> 33 <211> 2010 <212> DNA
<213> Artificial <220>
<223> Artificial sequence <400> 33 caggtgcagc tgcaggaatc agggcctggt ttggtgcggc cgagtcagac gctcagcttg 60 acttgtacgg tgtcaggtta ctctatcact agcgatcatg cctggagctg ggtacgacaa 120 ccaccgggtc ggggtctcga atggataggt tacataagct actcaggaat cacgacatac 180 aatccctccc ttaaaagtcg ggtcaccatg ctccgagaca ctagtaaaaa tcagttctcc 240 ctgcggttgt ccagcgtgac tgctgccgac acggcggtct attattgcgc aagaagtctg 300 gcgcggacaa cggcaatgga ctactgggga caaggttcac tggtaaccgt tagttcagca 360 agcaccaagg gtccgtctgt ctttccactc gcgccttcta gcaagtcaac ctcagggggg 420 actgccgcgc ttggatgtct ggtcaaagat tattttcctg agccggtaac agttagctgg 480 aattcaggtg ccctcacatc tggggtacac acgtttcccg ccgtgcttca gagctctggc 540 ctctacagtc tttctagcgt ggtcaccgtc ccatcttcat cattgggtac acaaacttac 600 atttgtaacg ttaatcacaa acctagcaac actaaggtgg ataaaaaagt agagccaaag 660 tcctgcgaca agactcacac ctgtcctccc tgtccagcac ccgaactttt gggcggtcct 720 tctgttttcc tgtttcctcc taaacccaaa gatacactca tgatctccag aaccccggaa 780 gtaacctgcg tagtcgtgga cgtatcccat gaggatcccg aggtaaaatt caactggtac 840 gtagacgggg tcgaggtgca caatgccaag actaaaccta gggaagagca atacaatagt 900 acgtacaggg tggtttccgt gctgaccgtc ctgcatcagg attggctcaa cgggaaagag 960 tataaatgta aggtgtcaaa caaagctttg ccggcaccaa tagagaaaac cattagtaag 1020 gcgaaaggac aaccccgaga gccacaagtg tatacgttgc ctcccagccg cgaggaaatg 1080 acgaagaatc aagtctctct gacttgtctg gtgaagggtt tttacccgtc tgatatagct 1140 gtcgaatggg agtctaacgg ccagccagag aataattaca aaaccactcc tccggtcttg 1200 gattctgatg ggagcttttt cctgtattcc aaattgacag ttgataaaag tcggtggcag 1260 caggggaacg tcttctcctg tagcgtcatg catgaagcac tgcataatca ttatacccaa 1320 aaaagtttgt ccttgagccc tggtggcgag ggttcagggg atggaggcga ggggtccggg 1380 gacggcgaag gctcagatac cggaagacca tttgtggaga tgtattccga aataccggag 1440 ataatacata tgacggaagg tcgagaactc gtcatcccat gtcgcgtaac ctctccaaat 1500 atcaccgtaa cactcaaaaa attccctctt gacacgttga taccggacgg caaaagaata 1560 atatgggatt caaggaaagg atttataata agcaacgcca catacaaaga gattgggctg 1620 ctcacttgtg aagccactgt taatgggcac ttgtataaga ctaattatct cacccaccgc 1680 cagacgaata ctataataga tgtcgttctg agcccaagtc atgggattga actttctgtt 1740 ggcgaaaagc tcgtgttgaa ttgcactgct aggacggagc tgaatgttgg tatagatttc 1800 aattgggaat atcctagctc taaacaccag cacaaaaaac tcgttaatcg cgacttgaag 1860 acgcagtcag gatcagagat gaaaaagttc ctctcaacgc tgactataga tggagtaacg 1920 agatccgacc agggattgta cacctgcgcc gcgtcttccg ggctcatgac aaaaaaaaac 1980 agcactttcg tacgcgtcca tgaaaaatag 2010 <210> 34 <211> 669 <212> PRT
<213> Artificial <220>
<223> Artificial sequence <400> 34 Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Arg Pro Ser Gln Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Tyr Ser Ile Thr Ser Asp His Ala Trp Ser Trp Val Arg Gln Pro Pro Gly Arg Gly Leu Glu Trp Ile Gly Tyr Ile Ser Tyr Ser Gly Ile Thr Thr Tyr Asn Pro Ser Leu Lys Ser Arg Val Thr Met Leu Arg Asp Thr Ser Lys Asn Gln Phe Ser Leu Arg Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys Ala Arg Ser Leu Ala Arg Thr Thr Ala Met Asp Tyr Trp Gly Gln Gly Ser Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gin Pro Arg Glu Pro Gin Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gin Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gin Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gin Gin Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gin Lys Ser Leu Ser Leu Ser Pro Gly Gly Glu Gly Ser Gly Asp Gly Gly Glu Gly Ser Gly Asp Gly Glu Gly Ser Asp Thr Gly Arg Pro Phe Val Glu Met Tyr Ser Glu Ile Pro Glu Ile Ile His Met Thr Glu Gly Arg Glu Leu Val Ile Pro Cys Arg Val Thr Ser Pro Asn Ile Thr Val Thr Leu Lys Lys Phe Pro Leu Asp Thr Leu Ile Pro Asp Gly Lys Arg Ile Ile Trp Asp Ser Arg Lys Gly Phe Ile Ile Ser Asn Ala Thr Tyr Lys Glu Ile Gly Leu Leu Thr Cys Glu Ala Thr Val Asn Gly His Leu Tyr Lys Thr Asn Tyr Leu Thr His Arg Gin Thr Asn Thr Ile Ile Asp Val Val Leu Ser Pro Ser His Gly Ile Glu Leu Ser Val Gly Glu Lys Leu Val Leu Asn Cys Thr Ala Arg Thr Glu Leu Asn Val Gly Ile Asp Phe Asn Trp Glu Tyr Pro Ser Ser Lys His Gin His Lys Lys Leu Val Asn Arg Asp Leu Lys Thr Gin Ser Gly Ser Glu Met Lys Lys Phe Leu Ser Thr Leu Thr Ile Asp Gly Val Thr Arg Ser Asp Gin Gly Leu Tyr Thr Cys Ala Ala Ser Ser Gly Leu Met Thr Lys Lys Asn Ser Thr Phe Val Arg Val His Glu Lys <210> 35 <211> 1308 <212> DNA
<213> Artificial <220>
<223> Artificial sequence <400> 35 gacattcaaa tgactcagtc tccatccagt ctctccgctt ctgtggggga ccgagtaacc 60 ataacatgtc gggcatctca ggacataagc tcatacttga attggtatca gcagaaacca 120 gggaaggcgc ccaagcttct tatctactat acatcaagac ttcatagcgg ggtgccaagc 180 cgattcagtg gcagcggttc aggaacagac tttacgttca ccatttcatc tttgcagcca 240 gaagatatag ctacgtacta ctgtcagcaa ggaaatacgt tgccgtacac ctttggccag 300 ggcacaaaag tcgaaattaa gcgaaccgta gcagccccga gtgtctttat ctttcctccc 360 tcagatgagc aacttaaaag cgggacagcc tcagtagttt gcctcctgaa caatttctac 420 ccacgggaag ccaaggtgca gtggaaggtg gacaatgctc ttcagtccgg caactctcag 480 gaaagtgtta ccgagcaaga ctctaaagac tcaacttaca gcctcagctc caccctcact 540 ttgtccaagg ctgattacga aaaacataag gtatatgcct gcgaagttac gcaccaagga 600 ctttcatccc cggtgacaaa gagcttcaac agaggcgaat gtggagaggg gtccggcgac 660 ggcggtgaag ggtctggtga tggggaaggt tccgataccg gtcgaccctt cgtcgagatg 720 tattctgaga ttccggaaat catccacatg accgaaggac gagagcttgt aattccttgc 780 cgagttacat cacccaacat aacggtgaca ctcaagaagt ttcctttgga tacattgatt 840 ccggacggga agcgcataat ttgggatagt agaaagggtt ttattatcag caacgctacg 900 tataaggaga taggtctgct cacttgtgaa gccactgtga atgggcacct gtacaaaaca 960 aattatctca cccaccgaca gactaacacc attatcgatg ttgttttgtc tccatctcat 1020 ggaatcgaac ttagtgtcgg agaaaagctc gtactgaatt gcacagcccg aacggaactt 1080 aatgttggga ttgactttaa ttgggagtat ccgtcttcta agcatcaaca caagaagctt 1140 gttaacaggg atctcaagac gcaatccgga tcagaaatga aaaaatttct ctccactctt 1200 actatagatg gagtcacacg ctccgaccaa ggtctctaca cgtgcgcagc tagtagtggt 1260 ctgatgacca aaaagaactc tacgttcgtg agagtacatg agaagtag 1308 <210> 36 <211> 435 <212> PRT
<213> Artificial <220>
<223> Artificial sequence <400> 36 Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Asp Ile Ser Ser Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile Tyr Tyr Thr Ser Arg Leu His Ser Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Phe Thr Ile Ser Ser Leu Gin Pro Glu Asp Ile Ala Thr Tyr Tyr Cys Gin Gin Gly Asn Thr Leu Pro Tyr Thr Phe Gly Gin Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gin Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gin Trp Lys Val Asp Asn Ala Leu Gin Ser Gly Asn Ser Gin Glu Ser Val Thr Glu Gin Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gin Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys Gly Glu Gly Ser Gly Asp Gly Gly Glu Gly Ser Gly Asp Gly Glu Gly Ser Asp Thr Gly Arg Pro Phe Val Glu Met Tyr Ser Glu Ile Pro Glu Ile Ile His Met Thr Glu Gly Arg Glu Leu Val Ile Pro Cys Arg Val Thr Ser Pro Asn Ile Thr Val Thr Leu Lys Lys Phe Pro Leu Asp Thr Leu Ile Pro Asp Gly Lys Arg Ile Ile Trp Asp Ser Arg Lys Gly Phe Ile Ile Ser Asn Ala Thr Tyr Lys Glu Ile Gly Leu Leu Thr Cys Glu Ala Thr Val Asn Gly His Leu Tyr Lys Thr Asn Tyr Leu Thr His Arg Gin Thr Asn Thr Ile Ile Asp Val Val Leu Ser Pro Ser His Gly Ile Glu Leu Ser Val Gly Glu Lys Leu Val Leu Asn Cys Thr Ala Arg Thr Glu Leu Asn Val Gly Ile Asp Phe Asn Trp Glu Tyr Pro Ser Ser Lys His Gin His Lys Lys Leu Val Asn Arg Asp Leu Lys Thr Gin Ser Gly Ser Glu Met Lys Lys Phe Leu Ser Thr Leu Thr Ile Asp Gly Val Thr Arg Ser Asp Gin Gly Leu Tyr Thr Cys Ala Ala Ser Ser Gly Leu Met Thr Lys Lys Asn Ser Thr Phe Val Arg Val His Glu Lys <210> 37 <211> 1995 <212> DNA
<213> Artificial <220>
<223> Artificial sequence <400> 37 caagtacaac ttcaagaatc aggtcccggg ctcgtgcggc cttcacaaac acttagcctc 60 acctgcactg tgtccgggta tagcataaca agtgaccacg cgtggagctg ggtgcggcag 120 cctcctggtc gcggcctcga gtggattgga tacatatcct actcaggaat cactacatat 180 aatccaagtt tgaaatcccg agttaccatg ttgagggaca cgagtaaaaa tcagttcagt 240 ctgaggttgt caagcgtaac ggcggctgat acggctgttt attactgtgc aagaagtttg 300 gcacgaacaa ccgcgatgga ctactggggt caaggctcat tggtaactgt gagctctgcg 360 tctaccaagg gccctagcgt ttttcctctg gccccttcct ccaagtccac gtccggtgga 420 acagctgctc tcggctgttt ggtaaaagat tatttcccag aacccgttac tgtgtcatgg 480 aactctggtg ctttgacaag tggagtccat acttttcctg ccgttctgca atcaagtggg 540 ctctatagct tgtcctcagt tgtcacagta ccatcatcaa gcctgggtac acagacttat 600 atatgcaatg tgaaccacaa gccttccaat acgaaagtcg acaagaaggt cgagcccaag 660 tcatgcgaca agacccatac ctgcccccca tgtccagccc ccgaactgct gggcggaccc 720 tcagtcttcc tctttccacc aaagccgaaa gataccctta tgatctctag gacccccgag 780 gtaacgtgcg ttgtcgtcga tgtgtctcac gaggacccgg aggtcaagtt caattggtac 840 gtcgatggcg tcgaggttca taacgcgaag actaaaccga gggaggaaca atacaactct 900 acgtaccgag tagtgtccgt gttgacagta ctgcatcaag attggctcaa tggtaaagaa 960 tataaatgca aggtctctaa caaagcgttg cctgcgccaa tcgaaaaaac tattagcaaa 1020 gctaagggtc aaccgcgaga gcctcaggta tacacgcttc ctccgtcccg agaagagatg 1080 acgaaaaatc aagtctccct gacatgtctt gttaagggtt tttacccttc tgacattgct 1140 gtcgaatggg agtccaatgg ccagcccgag aacaactata agacgacgcc tcccgtcttg 1200 gatagtgacg gaagcttttt cctgtattct aaattgaccg tggacaagag ccggtggcaa 1260 cagggtaacg tcttttcatg ctccgtaatg cacgaggcgc ttcataacca ctacacccaa 1320 aagagtctct cattgtctcc cggtggcggt tcaggtgggg ggggaagcgg tggtggatct 1380 gacactggac ggcctttcgt tgagatgtac tcagaaattc cggagatcat tcacatgaca 1440 gaagggaggg agttggtgat accttgccgg gttacatcac caaacataac tgtaacactc 1500 aaaaaattcc ccctggatac acttatccct gatggaaagc gaataatatg ggacagtaga 1560 aaaggattta tcattagcaa cgcaacgtat aaagaaatcg gattgcttac ctgcgaagcg 1620 acggtgaatg gccatctgta caaaacgaac tacctcacgc accgacaaac gaacactatc 1680 atagatgtag ttttgagtcc tagtcacggt attgagctca gcgtcgggga gaaactggtc 1740 cttaactgta ctgctagaac ggaactcaac gtgggtatag atttcaactg ggagtacccg 1800 tcatccaaac atcaacacaa gaaacttgtc aaccgagacc tgaagacaca atctggatca 1860 gagatgaaga agtttttgtc tactcttaca attgatgggg tcactcggtc tgatcaagga 1920 ctgtatacct gcgcagccag ttcagggttg atgactaaaa aaaattccac cttcgtacga 1980 gtccacgaga agtag 1995 <210> 38 <211> 664 <212> PRT
<213> Artificial <220>
<223> Artificial sequence <400> 38 Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Arg Pro Ser Gln Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Tyr Ser Ile Thr Ser Asp His Ala Trp Ser Trp Val Arg Gln Pro Pro Gly Arg Gly Leu Glu Trp Ile Gly Tyr Ile Ser Tyr Ser Gly Ile Thr Thr Tyr Asn Pro Ser Leu Lys Ser Arg Val Thr Met Leu Arg Asp Thr Ser Lys Asn Gln Phe Ser Leu Arg Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys Ala Arg Ser Leu Ala Arg Thr Thr Ala Met Asp Tyr Trp Gly Gln Gly Ser Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gin Pro Arg Glu Pro Gin Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gin Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gin Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gin Gin Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gin Lys Ser Leu Ser Leu Ser Pro Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Ser Asp Thr Gly Arg Pro Phe Val Glu Met Tyr Ser Glu Ile Pro Glu Ile Ile His Met Thr Glu Gly Arg Glu Leu Val Ile Pro Cys Arg Val Thr Ser Pro Asn Ile Thr Val Thr Leu Lys Lys Phe Pro Leu Asp Thr Leu Ile Pro Asp Gly Lys Arg Ile Ile Trp Asp Ser Arg Lys Gly Phe Ile Ile Ser Asn Ala Thr Tyr Lys Glu Ile Gly Leu Leu Thr Cys Glu Ala Thr Val Asn Gly His Leu Tyr Lys Thr Asn Tyr Leu Thr His Arg Gin Thr Asn Thr Ile Ile Asp Val Val Leu Ser Pro Ser His Gly Ile Glu Leu Ser Val Gly Glu Lys Leu Val Leu Asn Cys Thr Ala Arg Thr Glu Leu Asn Val Gly Ile Asp Phe Asn Trp Glu Tyr Pro Ser Ser Lys His Gin His Lys Lys Leu Val Asn Arg Asp Leu Lys Thr Gin Ser Gly Ser Glu Met Lys Lys Phe Leu Ser Thr Leu Thr Ile Asp Gly Val Thr Arg Ser Asp Gin Gly Leu Tyr Thr Cys Ala Ala Ser Ser Gly Leu Met Thr Lys Lys Asn Ser Thr Phe Val Arg Val His Glu Lys <210> 39 <211> 1293 <212> DNA
<213> Artificial <220>
<223> Artificial sequence <400> 39 gatattcaaa tgactcagtc tccttcaagc ctttccgcct cagtcggcga cagagtaaca 60 ataacttgtc gggcgtctca agatatctcc tcatatttga attggtacca gcaaaaaccc 120 ggtaaagcac caaagcttct catctactat acctcaagac tgcattccgg ggtgccgagc 180 cggtttagcg gatctggatc tggaacagac tttacattca cgatttccag cctgcagccg 240 gaggatattg ccacctatta ttgtcagcag ggaaacacgt tgccttacac tttcggacag 300 ggaaccaaag tggagataaa gaggactgtt gccgcaccga gcgtgtttat ctttcctcct 360 tcagatgagc agcttaagtc tggtacagcc tcagttgtat gtttgctgaa caacttctac 420 ccaagggaag ctaaagtaca gtggaaggtt gataatgccc ttcaatccgg gaactctcaa 480 gagtctgtaa cagaacaaga tagtaaggac tcaacgtata gcctttccag cacgttgacg 540 ctgagtaagg cagactatga aaagcacaag gtctacgcgt gcgaggtgac acaccaaggc 600 ctgtcttccc ctgtaaccaa aagctttaac aggggtgagt gcggtggaag cggcggcggc 660 ggttctggag gcgggtcaga cactggtcga ccgtttgtcg agatgtattc tgagatacct 720 gagattatcc acatgacaga aggacgggaa ctggtgatcc cttgccgggt aacctcaccc 780 aatatcaccg tgacattgaa aaagtttccc cttgacacac ttatacctga cggaaagagg 840 atcatttggg acagtcgcaa gggtttcatc atttccaacg caacatataa agagatagga 900 cttttgacgt gcgaagcgac ggtcaatggt cacttgtaca agacgaacta tttgacccat 960 agacaaacga acactataat agatgttgtg cttagtccaa gtcacgggat agaattgagt 1020 gtaggcgaga agcttgtact caattgtacg gcccgaaccg agctcaacgt tggaatagac 1080 ttcaactggg agtaccctag cagcaagcac caacataaga agcttgtaaa ccgcgatttg 1140 aagacgcagt caggcagtga aatgaaaaag ttcttgtcca ctttgacgat tgatggtgtt 1200 acgagatcag accagggctt gtatacctgc gcagcgtcaa gcgggctgat gacgaagaag 1260 aactcaactt ttgtcagagt tcacgaaaag tag 1293 <210> 40 <211> 430 <212> PRT
<213> Artificial <220>
<223> Artificial sequence <400> 40 Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Asp Ile Ser Ser Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile Tyr Tyr Thr Ser Arg Leu His Ser Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Phe Thr Ile Ser Ser Leu Gin Pro Glu Asp Ile Ala Thr Tyr Tyr Cys Gin Gin Gly Asn Thr Leu Pro Tyr Thr Phe Gly Gin Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gin Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gin Trp Lys Val Asp Asn Ala Leu Gin Ser Gly Asn Ser Gin Glu Ser Val Thr Glu Gin Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gin Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Ser Asp Thr Gly Arg Pro Phe Val Glu Met Tyr Ser Glu Ile Pro Glu Ile Ile His Met Thr Glu Gly Arg Glu Leu Val Ile Pro Cys Arg Val Thr Ser Pro Asn Ile Thr Val Thr Leu Lys Lys Phe Pro Leu Asp Thr Leu Ile Pro Asp Gly Lys Arg Ile Ile Trp Asp Ser Arg Lys Gly Phe Ile Ile Ser Asn Ala Thr Tyr Lys Glu Ile Gly Leu Leu Thr Cys Glu Ala Thr Val Asn Gly His Leu Tyr Lys Thr Asn Tyr Leu Thr His Arg Gin Thr Asn Thr Ile Ile Asp Val Val Leu Ser Pro Ser His Gly Ile Glu Leu Ser Val Gly Glu Lys Leu Val Leu Asn Cys Thr Ala Arg Thr Glu Leu Asn Val Gly Ile Asp Phe Asn Trp Glu Tyr Pro Ser Ser Lys His Gin His Lys Lys Leu Val Asn Arg Asp Leu Lys Thr Gin Ser Gly Ser Glu Met Lys Lys Phe Leu Ser Thr Leu Thr Ile Asp Gly Val Thr Arg Ser Asp Gin Gly Leu Tyr Thr Cys Ala Ala Ser Ser Gly Leu Met Thr Lys Lys Asn Ser Thr Phe Val Arg Val His Glu Lys <210> 41 <211> 1995 <212> DNA
<213> Artificial <220>
<223> Artificial sequence <400> 41 caagttcaac tgcaggagag cggcccgggt ttggtacgac caagccaaac actctcactt 60 acatgcaccg tgtcagggta tagcattacc tcagaccacg cgtggagctg ggtacggcag 120 ccgccgggtc gaggcctcga gtggataggg tatatctctt actcaggtat tacaacatac 180 aacccgtctc ttaagtctcg cgtgaccatg ctgcgggata caagcaaaaa ccagttctcc 240 ctcagactga gctctgtcac tgcggccgat actgctgtct actattgtgc tcgaagtttg 300 gcgaggacaa cggctatgga ctattggggc caaggatccc tggtaacagt ttcttctgca 360 agtacgaaag gcccaagtgt gtttccactg gctccctcct ctaagagcac ttctggggga 420 acggcagctc tgggctgcct tgtgaaggac tactttcctg agccagtaac agtctcctgg 480 aattcaggag cccttactag cggtgttcat acgttcccgg ccgttctgca gagtagcggg 540 ctttactctc tgtcatctgt tgtgacggtt ccatccagca gcttgggcac acagacctac 600 atatgcaatg tcaatcacaa accttctaat acaaaggtgg ataaaaaagt cgagcctaag 660 agttgcgata agacccatac ctgtcctcca tgtcccgcac cagaactttt gggcgggcca 720 tcagtgtttc tgttcccccc caagcctaaa gataccctta tgattagtag aacacccgaa 780 gtgacctgtg tagtagtgga tgttagccat gaggaccctg aagttaaatt caattggtat 840 gtcgatgggg ttgaagttca caatgccaaa actaagcccc gcgaagaaca gtataacagt 900 acatataggg tcgtttcagt actgacagta ttgcaccagg actggttgaa cggaaaggag 960 tataagtgca aagtcagcaa caaagccctg cctgcaccta tcgaaaaaac catcagtaag 1020 gcaaagggac agccgaggga accgcaggtg tacacgctcc ccccgtccag agaagagatg 1080 acaaagaacc aggtcagcct gacatgtttg gtcaagggat tctatccgtc agacattgcc 1140 gtcgagtggg agagtaatgg ccagcccgag aataattata aaactactcc gcccgtgctt 1200 gactccgacg ggtcattttt cctctatagc aaactgaccg tggataagtc aagatggcaa 1260 caaggtaacg tctttagttg tagtgttatg catgaggcgc ttcataacca ctatacacag 1320 aagagtttga gtttgtcacc tggtgggggg agcggtggtg gaggttctgg tggtggttat 1380 agcatgactc cacccaccct gaacatcact gaagaatcac atgtcatcga cactggtgac 1440 tccttgtcca taagttgccg ggggcaacac cctctggaat gggcctggcc cggtgcacag 1500 gaggccccag cgactggcga caaggactca gaggacacgg gggttgtcag agattgtgag 1560 gggactgacg cgaggccgta ttgcaaagtt ctgctgcttc atgaagtgca cgcaaacgat 1620 acgggatctt acgtgtgcta ctacaaatat ataaaggccc ggattgaagg tacgacagcg 1680 gcttcaagct acgtattcgt tagggatttc gagcaaccat tcatcaacaa gcctgataca 1740 ttgttggtta accgaaaaga cgccatgtgg gtcccttgcc tcgtctccat tccgggactt 1800 aatgtaacac tcaggagcca aagttccgtc ttgtggcccg acggccaaga agtagtttgg 1860 gacgacaggc gaggcatgct cgtgagtacg ccgctgcttc atgatgcgct gtaccttcaa 1920 tgcgagacga cttggggtga ccaagacttt ctctctaacc cttttctggt ccatatcaca 1980 gggaacgagc tctag 1995 <210> 42 <211> 664 <212> PRT
<213> Artificial <220>
<223> Artificial sequence <400> 42 Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Arg Pro Ser Gln Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Tyr Ser Ile Thr Ser Asp His Ala Trp Ser Trp Val Arg Gln Pro Pro Gly Arg Gly Leu Glu Trp Ile Gly Tyr Ile Ser Tyr Ser Gly Ile Thr Thr Tyr Asn Pro Ser Leu Lys Ser Arg Val Thr Met Leu Arg Asp Thr Ser Lys Asn Gln Phe Ser Leu Arg Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys Ala Arg Ser Leu Ala Arg Thr Thr Ala Met Asp Tyr Trp Gly Gln Gly Ser Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gin Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gin Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gin Gin Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gin Lys Ser Leu Ser Leu Ser Pro Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Tyr Ser Met Thr Pro Pro Thr Leu Asn Ile Thr Glu Glu Ser His Val Ile Asp Thr Gly Asp Ser Leu Ser Ile Ser Cys Arg Gly Gin His Pro Leu Glu Trp Ala Trp Pro Gly Ala Gin Glu Ala Pro Ala Thr Gly Asp Lys Asp Ser Glu Asp Thr Gly Val Val Arg Asp Cys Glu Gly Thr Asp Ala Arg Pro Tyr Cys Lys Val Leu Leu Leu His Glu Val His Ala Asn Asp Thr Gly Ser Tyr Val Cys Tyr Tyr Lys Tyr Ile Lys Ala Arg Ile Glu Gly Thr Thr Ala Ala Ser Ser Tyr Val Phe Val Arg Asp Phe Glu Gin Pro Phe Ile Asn Lys Pro Asp Thr Leu Leu Val Asn Arg Lys Asp Ala Met Trp Val Pro Cys Leu Val Ser Ile Pro Gly Leu Asn Val Thr Leu Arg Ser Gln Ser Ser Val Leu Trp Pro Asp Gly Gln Glu Val Val Trp Asp Asp Arg Arg Gly Met Leu Val Ser Thr Pro Leu Leu His Asp Ala Leu Tyr Leu Gln Cys Glu Thr Thr Trp Gly Asp Gln Asp Phe Leu Ser Asn Pro Phe Leu Val His Ile Thr Gly Asn Glu Leu <210> 43 <211> 1308 <212> DNA
<213> Artificial <220>
<223> Artificial sequence <400> 43 gacatacaaa tgactcaatc tcctagctca ctctccgcta gtgtgggcga tcgggtaacc 60 atcacatgtc gggccagcca ggacatatct tcatatctga attggtatca gcagaagcca 120 gggaaggccc ctaagctgct tatctactac acgtcaaggt tgcactcagg tgtcccgtct 180 cggttctctg gtagtgggtc cgggactgac tttacattca caattagtag cctccagccc 240 gaggacatag cgacttacta ctgccaacag ggtaatacct tgccctacac tttcggacaa 300 gggaccaagg ttgagattaa gcgaacggtc gctgctccca gtgtgttcat ttttcctccg 360 tctgatgaac agttgaaatc cgggaccgct agcgttgtgt gtctcctgaa taacttttac 420 ccaagggagg ccaaagttca atggaaagta gataacgcct tgcagagtgg aaacagccag 480 gagagtgtta ctgagcaaga ctcaaaagat tcaacctata gcctcagctc cactctcacg 540 ctgagcaaag ctgactacga aaagcacaag gtatatgcct gcgaagttac tcatcaagga 600 ctgagctctc cagtgacgaa gagtttcaac cggggggaat gcggcgaagg ctccggagac 660 ggcggtgagg gaagcggcga tggagagggg tccgatactg gccgcccctt tgtggagatg 720 tattctgaga tcccggagat tatacacatg actgagggac gagagctcgt tatcccatgt 780 cgagtaacga gtccgaatat aacggtcacg ctcaaaaaat ttcccttgga taccttgata 840 ccagatggta agcgaataat ctgggattct cggaaagggt ttattatctc aaacgctacg 900 tacaaagaaa tagggctttt gacttgtgag gctacagtta atggacatct ttataaaacg 960 aattatctta cgcaccgaca gacaaacacc ataatagatg ttgtcctttc tccctctcat 1020 ggaattgagt tgagcgtggg tgaaaagttg gtgctgaact gcaccgctcg cactgagctt 1080 aatgtcggaa ttgattttaa ttgggagtac ccttcaagca aacatcagca taagaaactg 1140 gtaaatagag atcttaaaac acagtcaggt agcgaaatga aaaagttcct gagtacgttg 1200 acaatcgacg gtgtgactag atccgatcaa ggtctctata catgtgccgc cagttctggt 1260 ctgatgacca aaaagaatag tacatttgtt cgagttcacg agaaatag 1308 <210> 44 <211> 435 <212> PRT
<213> Artificial <220>
<223> Artificial sequence <400> 44 Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Asp Ile Ser Ser Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile Tyr Tyr Thr Ser Arg Leu His Ser Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Phe Thr Ile Ser Ser Leu Gln Pro Glu Asp Ile Ala Thr Tyr Tyr Cys Gin Gin Gly Asn Thr Leu Pro Tyr Thr Phe Gly Gin Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gin Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gin Trp Lys Val Asp Asn Ala Leu Gin Ser Gly Asn Ser Gin Glu Ser Val Thr Glu Gin Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gin Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys Gly Glu Gly Ser Gly Asp Gly Gly Glu Gly Ser Gly Asp Gly Glu Gly Ser Asp Thr Gly Arg Pro Phe Val Glu Met Tyr Ser Glu Ile Pro Glu Ile Ile His Met Thr Glu Gly Arg Glu Leu Val Ile Pro Cys Arg Val Thr Ser Pro Asn Ile Thr Val Thr Leu Lys Lys Phe Pro Leu Asp Thr Leu Ile Pro Asp Gly Lys Arg Ile Ile Trp Asp Ser Arg Lys Gly Phe Ile Ile Ser Asn Ala Thr Tyr Lys Glu Ile Gly Leu Leu Thr Cys Glu Ala Thr Val Asn Gly His Leu Tyr Lys Thr Asn Tyr Leu Thr His Arg Gin Thr Asn Thr Ile Ile Asp Val Val Leu Ser Pro Ser His Gly Ile Glu Leu Ser Val Gly Glu Lys Leu Val Leu Asn Cys Thr Ala Arg Thr Glu Leu Asn Val Gly Ile Asp Phe Asn Trp Glu Tyr Pro Ser Ser Lys His Gin His Lys Lys Leu Val Asn Arg Asp Leu Lys Thr Gin Ser Gly Ser Glu Met Lys Lys Phe Leu Ser Thr Leu Thr Ile Asp Gly Val Thr Arg Ser Asp Gin Gly Leu Tyr Thr Cys Ala Ala Ser Ser Gly Leu Met Thr Lys Lys Asn Ser Thr Phe Val Arg Val His Glu Lys <210> 45 <211> 1995 <212> DNA
<213> Artificial <220>
<223> Artificial sequence <400> 45 caagtacaat tgcaagagag cggcccaggt ctcgtaaggc cgtcccagac tttgtctctg 60 acatgcacag tatcagggta ttccatcact agtgatcacg cttggtcctg ggtccgacag 120 ccgcctggga gaggcctgga gtggataggg tacatctcct actccggaat aacgacgtac 180 aacccgagtc tgaagtctcg agtaaccatg ctgagggata caagcaagaa tcagttttca 240 ttgaggctct catccgttac agccgccgac acagctgtct attattgcgc tcgcagtttg 300 gccagaacca ctgcaatgga ttactggggc caaggatccc tggttaccgt cagctcagct 360 agcacgaaag gtccatctgt tttcccactt gcaccgtcca gtaagtccac ctcaggcgga 420 accgctgccc ttggatgcct ggtcaaggat tatttccccg agccagtcac agtcagctgg 480 aactctggag ccctcaccag cggagttcac acgtttcccg ctgtcttgca aagttccggg 540 ctctacagtc tgagctctgt agtaaccgtg cccagttcaa gccttgggac ccaaacttac 600 atatgtaatg taaatcacaa gccaagcaac actaaggtgg ataaaaaagt cgagccgaaa 660 tcctgcgaca aaacacacac gtgtcctccg tgtccggctc ccgaattgct tggcggcccc 720 tccgtgtttc tgttcccacc gaagccaaag gacactctga tgatctctcg cacgccagaa 780 gtgacatgcg tcgttgtaga cgtatcacac gaagaccccg aagttaagtt taactggtat 840 gtggatggag tcgaagtaca taatgccaag acgaaaccaa gggaagaaca atacaattct 900 acatatcggg tcgtgagtgt tctgacggta ttgcatcaag attggctcaa cggtaaagaa 960 tacaaatgta aggtgagtaa taaagcgctt cccgctccaa tagagaagac aatatccaaa 1020 gctaaaggtc agccacggga gccgcaagtt tataccttgc cgccttcaag agaagagatg 1080 acaaaaaacc aggtttccct tacgtgcctg gtgaagggat tttacccaag tgatatagca 1140 gttgaatggg agagcaacgg tcaaccagaa aacaactaca agactactcc cccagttctc 1200 gactctgatg ggtctttctt tttgtactca aaactcaccg ttgacaaatc aagatggcag 1260 caaggcaacg ttttttcatg tagcgtcatg catgaggcct tgcacaacca ctacacgcaa 1320 aaaagcctca gtttgagtcc cgggggtggt agtggcggtg gcggttccgg cggtgggtat 1380 tctatgacac cacccacgct caatattaca gaggagagcc acgtaattga tacaggtgat 1440 tctctgtcca ttagttgcag gggtcaacat ccgctggaat gggcctggcc gggtgcgcaa 1500 gaagcacccg caacaggaga taaagactcc gaagatacgg gggtggtcag agattgtgaa 1560 gggacagatg caaggcctta ttgtaaggtt ttgcttctcc acgaggtaca tgcgaacgat 1620 actgggtctt acgtgtgtta ctacaagtat atcaaagcta ggatcgaggg gactaccgcc 1680 gcgagttctt atgtttttgt ccgagacttc gagcagccgt tcatcaataa acctgacaca 1740 ctgttggtaa accggaaaga cgccatgtgg gtgccttgtc ttgtttctat cccgggtctg 1800 aacgtcactc ttaggagtca gtccagcgtc ctctggcccg atggccagga ggtcgtctgg 1860 gatgacagaa ggggcatgtt ggtatccact ccgcttttgc acgatgcgct gtaccttcag 1920 tgtgagacca cttggggtga ccaagatttt ctctcaaatc cctttctggt ccacataacc 1980 ggcaacgagc tctag 1995 <210> 46 <211> 664 <212> PRT
<213> Artificial <220>
<223> Artificial sequence <400> 46 Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Arg Pro Ser Gln Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Tyr Ser Ile Thr Ser Asp His Ala Trp Ser Trp Val Arg Gln Pro Pro Gly Arg Gly Leu Glu Trp Ile Gly Tyr Ile Ser Tyr Ser Gly Ile Thr Thr Tyr Asn Pro Ser Leu Lys Ser Arg Val Thr Met Leu Arg Asp Thr Ser Lys Asn Gln Phe Ser Leu Arg Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys Ala Arg Ser Leu Ala Arg Thr Thr Ala Met Asp Tyr Trp Gly Gln Gly Ser Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gin Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gin Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gin Gin Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gin Lys Ser Leu Ser Leu Ser Pro Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Tyr Ser Met Thr Pro Pro Thr Leu Asn Ile Thr Glu Glu Ser His Val Ile Asp Thr Gly Asp Ser Leu Ser Ile Ser Cys Arg Gly Gin His Pro Leu Glu Trp Ala Trp Pro Gly Ala Gin Glu Ala Pro Ala Thr Gly Asp Lys Asp Ser Glu Asp Thr Gly Val Val Arg Asp Cys Glu Gly Thr Asp Ala Arg Pro Tyr Cys Lys Val Leu Leu Leu His Glu Val His Ala Asn Asp Thr Gly Ser Tyr Val Cys Tyr Tyr Lys Tyr Ile Lys Ala Arg Ile Glu Gly Thr Thr Ala Ala Ser Ser Tyr Val Phe Val Arg Asp Phe Glu Gin Pro Phe Ile Asn Lys Pro Asp Thr Leu Leu Val Asn Arg Lys Asp Ala Met Trp Val Pro Cys Leu Val Ser Ile Pro Gly Leu Asn Val Thr Leu Arg Ser Gln Ser Ser Val Leu Trp Pro Asp Gly Gln Glu Val Val Trp Asp Asp Arg Arg Gly Met Leu Val Ser Thr Pro Leu Leu His Asp Ala Leu Tyr Leu Gln Cys Glu Thr Thr Trp Gly Asp Gln Asp Phe Leu Ser Asn Pro Phe Leu Val His Ile Thr Gly Asn Glu Leu <210> 47 <211> 1292 <212> DNA
<213> Artificial <220>
<223> Artificial sequence <400> 47 gacatacaga tgacccagtc ccctagtagc ctcagcgcaa gcgttggaga tcgggtgact 60 ataacgtgcc gagcgtccca agacatttct tcttatttga attggtatca acaaaaacca 120 gggaaagccc cgaaactgct gatttattac accagtcgac tgcactccgg agtccctagt 180 cggttcagcg ggtctggatc aggtactgat tttaccttta ctataagctc actccagcca 240 gaggacattg cgacctatta ttgccagcag ggaaacacac ttccgtacac gtttggccag 300 gggaccaaag ttgaaatcaa gaggaccgtg gcagcccctc agttttcata ttccctccgt 360 ctgacgagca gttgaagtca gggactgcat ccgtggtgtg tctgctgaat aatttctacc 420 cacgcgaggc caaggtgcag tggaaggtag ataatgctct ccaatccggg aacagccaag 480 agtctgttac tgaacaagat tccaaagact ctacctatag cctctcaagc acccttacac 540 ttagtaaggc ggattacgaa aaacacaaag tctacgcatg tgaagtgacc catcagggtc 600 tcagcagccc ggtcactaaa agctttaaca ggggggaatg tggggggagt ggtggtggag 660 gtagcggcgg tggctccgac accggaaggc ctttcgtaga gatgtattca gaaattcccg 720 aaattataca tatgacggaa ggcagagagc tggtcatacc gtgtagagta acatcaccca 780 acataactgt tacgcttaaa aagttcccac ttgacacact tatacccgac ggcaagagaa 840 taatctggga cagcagaaaa ggtttcatca tctccaatgc tacttataaa gagatcgggc 900 tcctgacgtg cgaggcgacc gtaaacgggc atttgtacaa aaccaactat ctcactcata 960 gacaaacaaa cactattatt gatgtggtgc tcagcccctc tcatgggatc gagctttccg 1020 taggtgaaaa gctggtcctg aactgcacag cacggactga gttgaatgta gggatagatt 1080 tcaactggga atacccgtct tcaaaacatc agcacaaaaa gcttgtgaat cgcgacctca 1140 agacacaatc agggtcagaa atgaaaaagt ttctctcaac gctgactatc gacggcgtca 1200 cgcggtccga tcagggcctt tacacttgtg cggcctcttc tgggttgatg acgaagaaaa 1260 acagtacgtt tgtacgcgta catgagaagt ag 1292 <210> 48 <211> 430 <212> PRT
<213> Artificial <220>
<223> Artificial sequence <400> 48 Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Asp Ile Ser Ser Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile Tyr Tyr Thr Ser Arg Leu His Ser Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Phe Thr Ile Ser Ser Leu Gln Pro Glu Asp Ile Ala Thr Tyr Tyr Cys Gin Gin Gly Asn Thr Leu Pro Tyr Thr Phe Gly Gin Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gin Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gin Trp Lys Val Asp Asn Ala Leu Gin Ser Gly Asn Ser Gin Glu Ser Val Thr Glu Gin Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gin Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Ser Asp Thr Gly Arg Pro Phe Val Glu Met Tyr Ser Glu Ile Pro Glu Ile Ile His Met Thr Glu Gly Arg Glu Leu Val Ile Pro Cys Arg Val Thr Ser Pro Asn Ile Thr Val Thr Leu Lys Lys Phe Pro Leu Asp Thr Leu Ile Pro Asp Gly Lys Arg Ile Ile Trp Asp Ser Arg Lys Gly Phe Ile Ile Ser Asn Ala Thr Tyr Lys Glu Ile Gly Leu Leu Thr Cys Glu Ala Thr Val Asn Gly His Leu Tyr Lys Thr Asn Tyr Leu Thr His Arg Gin Thr Asn Thr Ile Ile Asp Val Val Leu Ser Pro Ser His Gly Ile Glu Leu Ser Val Gly Glu Lys Leu Val Leu Asn Cys Thr Ala Arg Thr Glu Leu Asn Val Gly Ile Asp Phe Asn Trp Glu Tyr Pro Ser Ser Lys His Gin His Lys Lys Leu Val Asn Arg Asp Leu Lys Thr Gin Ser Gly Ser Glu Met Lys Lys Phe Leu Ser Thr Leu Thr Ile Asp Gly Val Thr Arg Ser Asp Gin Gly Leu Tyr Thr Cys Ala Ala Ser Ser Gly Leu Met Thr Lys Lys Asn Ser Thr Phe Val Arg Val His Glu Lys <210> 49 <211> 446 <212> PRT
<213> Artificial <220>
<223> Artificial sequence <400> 49 Glu Val Gin Leu Val Glu Ser Gly Gly Gly Leu Val Gin Pro Gly Arg Ser Leu Arg Leu Ser Cys Ala Ala Ser Arg Phe Thr Phe Asp Asp Tyr Ala Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ser Gly Ile Ser Trp Asn Ser Gly Arg Ile Gly Tyr Ala Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Glu Asn Ser Leu Phe Leu Gln Met Asn Gly Leu Arg Ala Glu Asp Thr Ala Leu Tyr Tyr Cys Ala Lys Gly Arg Asp Ser Phe Asp Ile Trp Gly Gln Gly Thr Met Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys <210> 50 <211> 214 <212> PRT

<213> Artificial <220>
<223> Artificial sequence <400> 50 Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Val Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Gly Ile Ser Ser Trp Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile Tyr Gly Ala Ser Ser Leu Glu Ser Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala Ser Tyr Tyr Cys Gln Gln Ala Asn Ser Phe Pro Tyr Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys <210> 51 <211> 443 <212> PRT
<213> Artificial <220>
<223> Artificial sequence <400> 51 Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys Ala Val Ser Gly His Ser Ile Ser His Asp His Ala Trp Ser Trp Val Arg Gln Pro Pro Gly Glu Gly Leu Glu Trp Ile Gly Phe Ile Ser Tyr Ser Gly Ile Thr Asn Tyr Asn Pro Ser Leu Gln Gly Arg Val Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg Ser Leu Ala Arg Thr Thr Ala Met Asp Tyr Trp Gly Glu Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Asn Phe Gly Thr Gln Thr Tyr Thr Cys Asn Val Asp His Lys Pro Ser Asn Thr Lys Val Asp Lys Thr Val Glu Arg Lys Ser Cys Val Glu Cys Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Phe Arg Val Val Ser Val Leu Thr Val Val His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Thr Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gin Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Met Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gin Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Ala His Tyr Thr Gin Lys Ser Leu Ser Leu Ser Pro <210> 52 <211> 214 <212> PRT
<213> Artificial <220>
<223> Artificial sequence <400> 52 Asp Ile Gin Met Thr Gin Ser Pro Ser Ser Leu Ser Ala Ser Val Gly Asp Ser Val Thr Ile Thr Cys Gin Ala Ser Thr Asp Ile Ser Ser His Leu Asn Trp Tyr Gin Gin Lys Pro Gly Lys Ala Pro Glu Leu Leu Ile Tyr Tyr Gly Ser His Leu Leu Ser Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Phe Thr Ile Ser Ser Leu Glu Ala Glu Asp Ala Ala Thr Tyr Tyr Cys Gly Gin Gly Asn Arg Leu Pro Tyr Thr Phe Gly Gin Gly Thr Lys Val Glu Ile Glu Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gin Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gin Trp Lys Val Asp Asn Ala Leu Gin Ser Gly Asn Ser Gin Glu Ser Val Thr Glu Gin Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gin Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys <210> 53 <211> 6 <212> PRT
<213> Artificial <220>
<223> Artificial sequence <400> 53 Ser Asp His Ala Trp Ser <210> 54 <211> 16 <212> PRT
<213> Artificial <220>
<223> Artificial sequence <400> 54 Tyr Ile Ser Tyr Ser Gly Ile Thr Thr Tyr Asn Pro Ser Leu Lys Ser <210> 55 <211> 10 <212> PRT
<213> Artificial <220>
<223> Artificial sequence <400> 55 Ser Leu Ala Arg Thr Thr Ala Met Asp Tyr <210> 56 <211> 11 <212> PRT
<213> Artificial <220>
<223> Artificial sequence <400> 56 Arg Ala Ser Gln Asp Ile Ser Ser Tyr Leu Asn <210> 57 <211> 7 <212> PRT
<213> Artificial <220>
<223> Artificial sequence <400> 57 Tyr Thr Ser Arg Leu His Ser <210> 58 <211> 9 <212> PRT

<213> Artificial <220>
<223> Artificial sequence <400> 58 Gln Gln Gly Asn Thr Leu Pro Tyr Thr <210> 59 <211> 2103 <212> DNA
<213> Artificial <220>
<223> Artificial sequence <400> 59 atgccgctct tgctccttct tccattgctc tgggcgggcg cactggccga tatccaaatg 60 acgcaaagtc caagttctct ttcagccagc gtcggagata gagtcactat aacatgccgc 120 gcgagccagg atatatcaag ctaccttaat tggtatcaac aaaaaccggg taaagcgccg 180 aaactcttga tttattatac cagtaggctc cactccggtg taccaagtcg gttcagtggc 240 tccgggagtg gaaccgactt cacatttaca ataagctctt tgcaaccaga ggatattgca 300 acttactatt gccagcaagg caacacgttg ccttacacgt ttggacaggg aacaaaggtt 360 gagataaagc gagggggcgg tggcagtggt ggagggggta gcggaggcgg ggggagtcaa 420 gtccagctcc aagagtccgg accaggcttg gtcagaccta gccagacgct tagcttgaca 480 tgtacggtga gtggctattc aattacatcc gatcatgctt ggagctgggt ccggcaacct 540 ccaggcagag gattggagtg gattggttat atctcttatt ctggtattac cacatataac 600 ccatcactca aaagtcgggt tactatgctg cgggacacct ccaaaaacca attttccctt 660 cggctgtcat cagtgaccgc ggcggataca gcggtgtatt attgtgcgcg cagcttggcc 720 cgcacaactg caatggatta ctggggtcaa ggttctcttg ttactgttag ttcagataaa 780 actcatacgt gtcccccttg tccagcacca gaattgctgg gaggcccctc tgtgtttttg 840 tttcctccca agccaaaaga cacccttatg atcagtcgga ctccagaagt cacgtgcgtt 900 gtggttgatg tgtcacacga ggatccagaa gtgaaattca actggtacgt tgatggcgtt 960 gaggtccata atgcaaaaac caaaccaaga gaagaacaat ataacagcac ataccgggtg 1020 gtctccgttc tgactgtgtt gcaccaggac tggttgaatg gtaaggaata taagtgcaag 1080 gtgtcaaaca aagcgttgcc tgctccgatc gaaaaaacaa tatccaaggc aaaaggtcaa 1140 ccccgcgagc ctcaagtata tactctccct cctagccgcg acgagttgac aaagaaccag 1200 gtttccttga catgtcttgt caaagggttc tacccgtccg atatagctgt tgaatgggaa 1260 agtaatggcc agccggaaaa taattataaa actactccac cggtacttga ctcagatggt 1320 tcattcttcc tttactccaa acttacagtt gacaaatcca ggtggcaaca gggaaatgta 1380 ttttcttgta gtgttatgca cgaggcgctg cacaatcact atacacaaaa aagcctttct 1440 cttagcccag gagggggctc tggagggggt gggagtggcg gtggcagcga caccggacga 1500 ccgttcgtag agatgtactc tgaaatacca gagataatcc acatgactga aggacgggag 1560 ctggtgatac cctgcagggt aacatctccc aacattacgg tgactctcaa gaagttccct 1620 cttgatacac tgattccgga tggtaaacgg atcatatggg atagtcgaaa aggttttata 1680 atcagcaatg caacctataa ggagattggg ctcttgacct gcgaagccac tgttaatggg 1740 catctttata agacgaacta tcttacccat cgccagacaa acaccattat agatgtggtt 1800 ttgtccccta gtcacgggat agaactctca gtgggcgaga agctggtcct caattgtact 1860 gccaggaccg aacttaatgt gggtatcgat ttcaattggg aatatccatc ttcaaaacac 1920 caacacaaaa agctcgttaa cagggacttg aagacccaat ctggatctga gatgaagaag 1980 ttcctttcta cattgacaat tgacggcgtt acgcgaagcg accaaggctt gtatacttgc 2040 gcagcgtcat ccggtctgat gaccaaaaaa aacagcactt ttgtaagagt tcacgaaaag 2100 tag 2103 <210> 60 <211> 700 <212> PRT
<213> Artificial <220>
<223> Artificial sequence <400> 60 Met Pro Leu Leu Leu Leu Leu Pro Leu Leu Trp Ala Gly Ala Leu Ala Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gin Asp Ile Ser Ser Tyr Leu Asn Trp Tyr Gin Gin Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile Tyr Tyr Thr Ser Arg Leu His Ser Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Phe Thr Ile Ser Ser Leu Gin Pro Glu Asp Ile Ala Thr Tyr Tyr Cys Gin Gin Gly Asn Thr Leu Pro Tyr Thr Phe Gly Gin Gly Thr Lys Val Glu Ile Lys Arg Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gin Val Gin Leu Gin Glu Ser Gly Pro Gly Leu Val Arg Pro Ser Gin Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Tyr Ser Ile Thr Ser Asp His Ala Trp Ser Trp Val Arg Gin Pro Pro Gly Arg Gly Leu Glu Trp Ile Gly Tyr Ile Ser Tyr Ser Gly Ile Thr Thr Tyr Asn Pro Ser Leu Lys Ser Arg Val Thr Met Leu Arg Asp Thr Ser Lys Asn Gin Phe Ser Leu Arg Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys Ala Arg Ser Leu Ala Arg Thr Thr Ala Met Asp Tyr Trp Gly Gln Gly Ser Leu Val Thr Val Ser Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Ser Asp Thr Gly Arg Pro Phe Val Glu Met Tyr Ser Glu Ile Pro Glu Ile Ile His Met Thr Glu Gly Arg Glu Leu Val Ile Pro Cys Arg Val Thr Ser Pro Asn Ile Thr Val Thr Leu Lys Lys Phe Pro Leu Asp Thr Leu Ile Pro Asp Gly Lys Arg Ile Ile Trp Asp Ser Arg Lys Gly Phe Ile Ile Ser Asn Ala Thr Tyr Lys Glu Ile Gly Leu Leu Thr Cys Glu Ala Thr Val Asn Gly His Leu Tyr Lys Thr Asn Tyr Leu Thr His Arg Gln Thr Asn Thr Ile Ile Asp Val Val Leu Ser Pro Ser His Gly Ile Glu Leu Ser Val Gly Glu Lys Leu Val Leu Asn Cys Thr Ala Arg Thr Glu Leu Asn Val Gly Ile Asp Phe Asn Trp Glu Tyr Pro Ser Ser Lys His Gln His Lys Lys Leu Val Asn Arg Asp Leu Lys Thr Gln Ser Gly Ser Glu Met Lys Lys Phe Leu Ser Thr Leu Thr Ile Asp Gly Val Thr Arg Ser Asp Gin Gly Leu Tyr Thr Cys Ala Ala Ser Ser Gly Leu Met Thr Lys Lys Asn Ser Thr Phe Val Arg Val His Glu Lys <210> 61 <211> 2151 <212> DNA
<213> Artificial <220>
<223> Artificial sequence <400> 61 atgccgctgc ttttgctgct ccccctgttg tgggcgggtg cacttgccga catacagatg 60 acacagtccc cgtcatcact gagcgcatcc gtaggggacc gcgtcactat cacctgccgg 120 gcctctcaag acatatcctc ttaccttaac tggtaccaac aaaagccagg gaaggccccg 180 aaactcctca tatattatac aagccggctc catagcgggg tacccagtcg gtttagtggg 240 tccggctccg gaacggattt tacgtttact atcagtagcc tgcagccgga ggacattgcc 300 acgtactatt gtcagcaggg aaatactctc ccctatacat ttggacaagg cacgaaagtc 360 gaaattaaac gcggcggcgg tggatctggc gggggaggct cagggggtgg agggagccag 420 gtgcagctcc aggaatctgg gccagggttg gtaaggccct cccagacttt gagtctcaca 480 tgcaccgtct ctgggtattc tataacgtct gaccacgcgt ggagctgggt gcggcagccg 540 cctggacgcg gtctggagtg gataggatac atctcttaca gtggcatcac tacgtacaat 600 ccgtcactta agagccgcgt cactatgctc cgggacactt caaaaaacca gttttccctc 660 cgcttgtcta gtgtcacggc ggcggatacg gccgtctact attgtgcacg gtctttggca 720 cgaacaactg cgatggacta ttggggccaa ggttccctcg tgacggtctc cagtggtgga 780 tcagggggcg gaggatccgg cggcggtagc gggggtggtg gttccgacac ggggaggccc 840 tttgtggaaa tgtacagtga aataccagag attattcata tgacggaggg acgggaactc 900 gtaataccct gccgggtaac atcaccgaat attacggtta ctctcaaaaa attccccctc 960 gacacactca tcccagatgg caagagaata atatgggata gccggaaagg ctttatcatc 1020 tctaacgcga cctataaaga gataggcctg cttacgtgcg aggcgacagt taatggacat 1080

190 ctttataaaa cgaattacct tactcaccgg cagacgaaca cgataatcga cgtcgtcctg 1140 agtccttccc atggcataga gcttagcgtg ggagagaagt tggtcttgaa ttgcaccgcg 1200 cgcacagaat tgaatgtagg gattgacttt aactgggagt acccatcctc aaaacatcaa 1260 cataaaaagc tggtgaaccg ggatttgaag actcagagcg gatctgagat gaaaaagttc 1320 ctgtcaactc tcaccatcga tggagtaacc cgaagtgacc agggtcttta tacatgtgca 1380 gctagttcag gtcttatgac caagaaaaac tcaacgttcg ttcgcgtgca cgaaaagggt 1440 ggcagcggtg ggggagggag cggtggaggg gacaagaccc atacttgccc cccatgtcct 1500 gccccggaat tgctcggtgg gccatctgta ttccttttcc cacctaagcc caaggacacc 1560 ctcatgatta gccgaacacc ggaagtaact tgcgttgtcg tagatgtgtc tcacgaggat 1620 cccgaagtca aattcaactg gtacgtcgac ggcgtagagg tccataatgc taaaactaag 1680 ccccgcgaag aacaatataa ttccacgtac cgagtagtga gtgtgcttac cgtgcttcac 1740 caggactggt tgaacggaaa ggagtacaag tgtaaggtta gcaacaaggc gctcccggct 1800 ccgatagaaa agactatctc aaaggccaaa gggcagccaa gggagccgca ggtgtacaca 1860 ttgcctccct caagggatga gcttactaaa aaccaagtct ctctcacctg tctcgtaaag 1920 gggttttatc cctctgatat cgctgtggaa tgggaaagta acgggcaacc agaaaataat 1980 tacaaaacga ctccgccggt actggatagt gacggtagct tctttttgta cagcaagttg 2040 acagtagata aatctaggtg gcaacaaggt aacgtatttt cctgctcagt aatgcacgaa 2100 gcgctgcaca accattacac tcaaaaaagt ctgtcattgt cccctggcta g 2151 <210> 62 <211> 716 <212> PRT
<213> Artificial <220>
<223> Artificial sequence <400> 62 Met Pro Leu Leu Leu Leu Leu Pro Leu Leu Trp Ala Gly Ala Leu Ala Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly

191 Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gin Asp Ile Ser Ser Tyr Leu Asn Trp Tyr Gin Gin Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile Tyr Tyr Thr Ser Arg Leu His Ser Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Phe Thr Ile Ser Ser Leu Gin Pro Glu Asp Ile Ala Thr Tyr Tyr Cys Gin Gin Gly Asn Thr Leu Pro Tyr Thr Phe Gly Gin Gly Thr Lys Val Glu Ile Lys Arg Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gin Val Gin Leu Gin Glu Ser Gly Pro Gly Leu Val Arg Pro Ser Gin Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Tyr Ser Ile Thr Ser Asp His Ala Trp Ser Trp Val Arg Gin Pro Pro Gly Arg Gly Leu Glu Trp Ile Gly Tyr Ile Ser Tyr Ser Gly Ile Thr Thr Tyr Asn Pro Ser Leu Lys Ser Arg Val Thr Met Leu Arg Asp Thr Ser Lys Asn Gin Phe Ser Leu Arg Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys Ala Arg Ser Leu Ala Arg Thr Thr Ala Met Asp Tyr Trp Gly Gin Gly Ser Leu Val Thr Val

192 Ser Ser Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp Thr Gly Arg Pro Phe Val Glu Met Tyr Ser Glu Ile Pro Glu Ile Ile His Met Thr Glu Gly Arg Glu Leu Val Ile Pro Cys Arg Val Thr Ser Pro Asn Ile Thr Val Thr Leu Lys Lys Phe Pro Leu Asp Thr Leu Ile Pro Asp Gly Lys Arg Ile Ile Trp Asp Ser Arg Lys Gly Phe Ile Ile Ser Asn Ala Thr Tyr Lys Glu Ile Gly Leu Leu Thr Cys Glu Ala Thr Val Asn Gly His Leu Tyr Lys Thr Asn Tyr Leu Thr His Arg Gin Thr Asn Thr Ile Ile Asp Val Val Leu Ser Pro Ser His Gly Ile Glu Leu Ser Val Gly Glu Lys Leu Val Leu Asn Cys Thr Ala Arg Thr Glu Leu Asn Val Gly Ile Asp Phe Asn Trp Glu Tyr Pro Ser Ser Lys His Gin His Lys Lys Leu Val Asn Arg Asp Leu Lys Thr Gin Ser Gly Ser Glu Met Lys Lys Phe Leu Ser Thr Leu Thr Ile Asp Gly Val Thr Arg Ser Asp Gin Gly Leu Tyr Thr Cys Ala Ala Ser Ser Gly

193 Leu Met Thr Lys Lys Asn Ser Thr Phe Val Arg Val His Glu Lys Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln

194 Gin Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gin Lys Ser Leu Ser Leu Ser Pro Gly <210> 63 <211> 2799 <212> DNA
<213> Artificial <220>
<223> Artificial sequence <400> 63 atgccattgc ttctcttgct gccactcctt tgggctggag ccctcgctga cattcaaatg 60 acccagagtc cgtcttcact ttctgcctcc gttggggata gagtgacgat cacgtgccgc 120 gcgtcacaag acatctctag ttacctcaac tggtatcagc aaaagcccgg taaagctcca 180 aaacttctca tctactatac ttctagattg cactccggcg taccgtctag gttttcaggt 240 agtggtagcg gcaccgactt cacttttacg atatcctctt tgcagcccga ggatatcgct 300 acttactatt gtcaacaagg aaacacgctt ccgtacacct tcggtcaagg gaccaaggta 360 gaaatcaaaa ggggtggcgg tggatcaggt ggcgggggat ccggaggggg tggatcccag 420 gtacaattgc aagagtctgg ccccggtctc gtcaggccat cccaaacttt gtcactgact 480 tgtacggtta gcggttacag tataaccagc gatcacgcgt ggagctgggt ccgacagccc 540 cccgggcggg gattggaatg gatcgggtat atctcctact caggaataac cacttacaat 600 ccatccctga aatcccgagt tacgatgctt agggatacaa gtaaaaacca gttctctctg 660 aggcttagct ctgtgactgc cgccgacaca gcggtttatt actgtgcacg gtcactggcg 720 aggaccacgg cgatggacta ttggggccag ggatcactcg tgactgtaag ctcagggggg 780 tcaggaggtg gtggctcagg tggtggaagt ggtgggggcg ggtcagacac gggaaggccg 840 tttgtagaaa tgtatagtga gataccggaa attatacaca tgaccgaagg ccgagaactc 900 gtcataccct gcagagttac ttcacctaac ataacggtca cgcttaaaaa atttcccctg 960 gacaccctga tacctgacgg gaaacggatc atatgggact caaggaaagg gtttatcatc 1020 tccaatgcta cttataaaga gatcgggctc ctgacttgtg aagccaccgt aaacggtcat 1080

195 ctttataaga ccaactacct cactcatcga cagacgaata cgataattga tgtcgtgctt 1140 agtccaagcc acggtattga gttgtcagtg ggcgagaaac tggtgctcaa ttgcacagca 1200 agaacggagc ttaacgtggg tatagacttc aactgggagt atccctccag taaacaccaa 1260 cacaaaaaac tcgttaatag agatttgaag acccaaagcg gatcagagat gaagaaattt 1320 ttgagcactc tcacgataga tggcgtgacg cggtcagatc aggggctcta tacctgcgct 1380 gcctcctccg gtctcatgac aaaaaagaat agcacttttg ttagggtgca cgaaaaaggc 1440 ggcagcggag gggggggatc aggtggtgga gacaagacac atacttgccc accgtgtccc 1500 gctccggaac tgcttggcgg gcctagcgtc ttcctcttcc cgcctaagcc gaaagacacc 1560 cttatgatct cacgaacgcc cgaggtgacg tgcgtcgttg ttgatgtgag ccacgaagat 1620 ccagaagtta agttcaattg gtacgtcgac ggggtggaag tacacaatgc gaagaccaaa 1680 ccgagggagg agcagtataa ttcaacatac agagtcgttt ctgtcctcac ggttctccac 1740 caggattggt tgaacggcaa agaatataaa tgcaaagtga gcaataaggc tctccccgct 1800 cccatcgaaa agacaatctc taaggctaaa ggccagccga gagaaccgca ggtttatacc 1860 ctcccaccct cacgcgacga gttgactaag aaccaggtca gccttacgtg tttggtgaag 1920 gggttctatc cgtctgacat cgcggtcgaa tgggaatcta acggtcaacc cgagaataac 1980 tataaaacta ccccaccagt tttggactca gacgggtcct ttttcctgta cagcaagctc 2040 acggtcgaca aatcccggtg gcagcaggga aatgttttca gttgcagtgt catgcacgaa 2100 gcattgcata atcattacac acaaaaatca ctcagcctga gccctggggg gggtagtggc 2160 gggggaggaa gcggtggagg atactctatg actccgccaa cacttaacat tactgaggag 2220 agccacgtca ttgatacggg ggactctttg tccatttcct gcagaggcca gcatccgctc 2280 gaatgggcct ggcccggagc tcaagaggcc ccggcgactg gtgataaaga cagcgaggat 2340 acgggagtag taagagactg cgagggcact gacgcccgac cgtactgcaa ggtactcctc 2400 ctccatgaag tccatgctaa tgatacaggg agttacgtct gttactacaa atacatcaaa 2460 gcgaggatag aaggtacgac cgcggcttca tcttacgttt ttgttagaga ttttgagcaa 2520 ccctttataa ataaacccga taccctcctg gtcaatcgca aggacgccat gtgggtcccg 2580 tgcctggtgt caatcccagg acttaacgtc actctcagat ctcaaagctc tgtgctttgg 2640 cctgacggac aggaggttgt ttgggacgac agacggggca tgctcgtgtc aacccctctg 2700

196 cttcatgatg ccctctattt gcagtgtgag acgacgtggg gtgaccagga ttttctgtca 2760 aacccttttc tggtgcacat cacgggcaat gagctctag 2799 <210> 64 <211> 932 <212> PRT
<213> Artificial <220>
<223> Artificial sequence <400> 64 Met Pro Leu Leu Leu Leu Leu Pro Leu Leu Trp Ala Gly Ala Leu Ala Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Asp Ile Ser Ser Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile Tyr Tyr Thr Ser Arg Leu His Ser Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Phe Thr Ile Ser Ser Leu Gln Pro Glu Asp Ile Ala Thr Tyr Tyr Cys Gln Gln Gly Asn Thr Leu Pro Tyr Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Arg Pro Ser Gln Thr Leu Ser Leu Thr

197 Cys Thr Val Ser Gly Tyr Ser Ile Thr Ser Asp His Ala Trp Ser Trp Val Arg Gin Pro Pro Gly Arg Gly Leu Glu Trp Ile Gly Tyr Ile Ser Tyr Ser Gly Ile Thr Thr Tyr Asn Pro Ser Leu Lys Ser Arg Val Thr Met Leu Arg Asp Thr Ser Lys Asn Gin Phe Ser Leu Arg Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys Ala Arg Ser Leu Ala Arg Thr Thr Ala Met Asp Tyr Trp Gly Gin Gly Ser Leu Val Thr Val Ser Ser Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp Thr Gly Arg Pro Phe Val Glu Met Tyr Ser Glu Ile Pro Glu Ile Ile His Met Thr Glu Gly Arg Glu Leu Val Ile Pro Cys Arg Val Thr Ser Pro Asn Ile Thr Val Thr Leu Lys Lys Phe Pro Leu Asp Thr Leu Ile Pro Asp Gly Lys Arg Ile Ile Trp Asp Ser Arg Lys Gly Phe Ile Ile Ser Asn Ala Thr Tyr Lys Glu Ile Gly Leu Leu Thr Cys Glu Ala Thr Val Asn Gly His Leu Tyr Lys Thr Asn Tyr Leu Thr

198 His Arg Gin Thr Asn Thr Ile Ile Asp Val Val Leu Ser Pro Ser His Gly Ile Glu Leu Ser Val Gly Glu Lys Leu Val Leu Asn Cys Thr Ala Arg Thr Glu Leu Asn Val Gly Ile Asp Phe Asn Trp Glu Tyr Pro Ser Ser Lys His Gin His Lys Lys Leu Val Asn Arg Asp Leu Lys Thr Gin Ser Gly Ser Glu Met Lys Lys Phe Leu Ser Thr Leu Thr Ile Asp Gly Val Thr Arg Ser Asp Gin Gly Leu Tyr Thr Cys Ala Ala Ser Ser Gly Leu Met Thr Lys Lys Asn Ser Thr Phe Val Arg Val His Glu Lys Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gin Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gin Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys

199 Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Tyr Ser Met Thr Pro Pro Thr Leu Asn Ile Thr Glu Glu Ser His Val Ile Asp Thr Gly Asp Ser Leu Ser Ile Ser Cys Arg Gly Gln His Pro Leu Glu Trp Ala Trp Pro Gly Ala Gln Glu Ala Pro Ala Thr Gly Asp Lys Asp Ser Glu Asp Thr Gly Val Val Arg Asp Cys Glu Gly Thr Asp Ala Arg Pro Tyr Cys Lys Val Leu Leu

200 Leu His Glu Val His Ala Asn Asp Thr Gly Ser Tyr Val Cys Tyr Tyr Lys Tyr Ile Lys Ala Arg Ile Glu Gly Thr Thr Ala Ala Ser Ser Tyr Val Phe Val Arg Asp Phe Glu Gln Pro Phe Ile Asn Lys Pro Asp Thr Leu Leu Val Asn Arg Lys Asp Ala Met Trp Val Pro Cys Leu Val Ser Ile Pro Gly Leu Asn Val Thr Leu Arg Ser Gln Ser Ser Val Leu Trp Pro Asp Gly Gln Glu Val Val Trp Asp Asp Arg Arg Gly Met Leu Val Ser Thr Pro Leu Leu His Asp Ala Leu Tyr Leu Gln Cys Glu Thr Thr Trp Gly Asp Gln Asp Phe Leu Ser Asn Pro Phe Leu Val His Ile Thr Gly Asn Glu Leu <210> 65 <211> 2805 <212> DNA
<213> Artificial <220>
<223> Artificial sequence <400> 65 atgccgctgc tgttgcttct tcccctgctc tgggctgggg cactggccga catacaaatg 60 acccagtcac caagtagtct ctctgcaagc gtcggagacc gggtcacgat aacctgtcga 120 gcaagtcagg acattagtag ctacctgaac tggtatcagc agaagcctgg caaagccccg 180 aagctcctca tatactatac cagcagactg cacagtggtg taccatcccg attctccggc 240 tcaggatccg gaaccgactt cacgttcacc ataagcagtc ttcaacccga ggacatcgca 300

201 acttattact gtcaacaagg taacacactt ccatatacat tcggccaggg taccaaagtt 360 gagatcaaaa gaggaggcgg tggttccggg ggtggaggct ctggaggtgg cggatcccag 420 gtccagctcc aggaaagcgg tccgggtttg gtgagaccat ctcagacact gagcttgacg 480 tgtacggtaa gtggttactc tataacttcc gatcatgcgt ggtcctgggt acggcaaccc 540 cctggcagag gtctcgaatg gataggctat attagctatt ctggaattac cacatacaac 600 ccaagcctga aatctcgcgt caccatgctg cgcgatactt ccaagaatca attttctctg 660 cggttgtcaa gtgttacggc ggctgacact gccgtctact actgtgctcg atccctcgcg 720 cggacaacag ccatggatta ctggggccaa gggtcccttg tgacggtatc ctccggcggg 780 agtggtggcg ggggttccgg gggaggtagt ggtggggggg gttcagacac aggacgccca 840 tttgtcgaga tgtacagtga gatacctgaa ataattcaca tgacggaagg acgcgagctt 900 gtcataccat gccgcgtgac tagccctaat attacggtaa cactgaaaaa attcccactt 960 gatactctga ttccggacgg caagcgaatc atttgggact caaggaaagg tttcataata 1020 tccaacgcaa catataagga aatcggactc ctgacgtgcg aggcgacggt aaacggccac 1080 ctttataaga caaactatct tacgcaccgg caaactaata ctattataga cgttgtcctt 1140 tctccctctc acggcataga gttgagtgtc ggtgaaaaat tggtacttaa ttgcaccgcg 1200 agaacggaac ttaatgtcgg aattgatttc aattgggaat acccaagtag taaacaccag 1260 cataagaagc ttgtaaaccg cgatttgaaa acgcaatctg gatcagaaat gaaaaaattt 1320 ctcagtacgc ttacaataga tggggtaacc cgaagcgatc aaggactgta tacctgcgca 1380 gcgtctagtg gcctcatgac aaagaagaat tcaacattcg taagagttca cgagaagggt 1440 ggcggtggtt caggtggggg atcaggcggg ggcggttata gcatgacgcc cccgacattg 1500 aacattacag aagagtctca cgtaatagat acgggggatt ccctcagtat ttcctgccgc 1560 gggcaacacc cacttgaatg ggcgtggccc ggggctcaag aagcaccagc aaccggagac 1620 aaagatagcg aggatactgg tgtcgttcga gactgtgaag ggaccgatgc ccggccgtac 1680 tgtaaggttc tcctgttgca tgaggttcat gctaatgata cgggcagcta tgtgtgctac 1740 tataagtaca tcaaagcgcg gatcgaaggc actaccgccg cgtcttctta tgttttcgtg 1800 cgagattttg aacaaccatt tataaacaag ccggacactt tgctcgtcaa taggaaagac 1860 gccatgtggg ttccctgctt ggtgtccata cccggcctga atgttacact taggtcacag 1920

202 agctctgttt tgtggcctga cggacaggag gttgtttggg atgatagacg aggcatgctc 1980 gtgtcaactc cacttcttca cgatgcgctg tatctccaat gcgagactac gtggggagat 2040 caagactttc ttagcaatcc cttcctggtc cacattactg gaaatgagct tggtgggagc 2100 ggaggtgggg gctcaggagg tggggataag acccatactt gcccaccctg cccggcacct 2160 gaacttctcg gaggtccgtc agtgtttttg tttccgccaa agcctaaaga cacactgatg 2220 atttctcgga cgcccgaggt aacttgtgta gtcgtagacg tgtcccatga ggaccctgaa 2280 gttaaattca actggtacgt ggacggggtt gaagtacata atgcaaagac aaaaccccgg 2340 gaggagcagt ataacagtac ttacagagta gtctccgtgc tcaccgtact ccaccaagat 2400 tggctcaacg gcaaggagta caaatgcaaa gtgtcaaata aagcgttgcc tgctccaatt 2460 gaaaaaacaa tatccaaggc gaaggggcaa ccccgagagc ctcaggttta cacattgccg 2520 ccaagtcgag acgaattgac aaagaaccaa gttagcttga cctgcctcgt gaagggtttt 2580 tatccgagcg atatagccgt tgaatgggag tctaacgggc aaccggaaaa taactataaa 2640 accactccgc cggtgcttga cagcgacggt tcttttttcc tgtacagtaa actcaccgtt 2700 gataaatcta ggtggcagca gggtaacgtc tttagttgca gcgttatgca tgaggctctt 2760 cataatcatt atactcaaaa atctttgagt ctgtctcccg gatag 2805 <210> 66 <211> 934 <212> PRT
<213> Artificial <220>
<223> Artificial sequence <400> 66 Met Pro Leu Leu Leu Leu Leu Pro Leu Leu Trp Ala Gly Ala Leu Ala Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Asp Ile Ser Ser Tyr

203 Leu Asn Trp Tyr Gin Gin Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile Tyr Tyr Thr Ser Arg Leu His Ser Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Phe Thr Ile Ser Ser Leu Gin Pro Glu Asp Ile Ala Thr Tyr Tyr Cys Gin Gin Gly Asn Thr Leu Pro Tyr Thr Phe Gly Gin Gly Thr Lys Val Glu Ile Lys Arg Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gin Val Gin Leu Gin Glu Ser Gly Pro Gly Leu Val Arg Pro Ser Gin Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Tyr Ser Ile Thr Ser Asp His Ala Trp Ser Trp Val Arg Gin Pro Pro Gly Arg Gly Leu Glu Trp Ile Gly Tyr Ile Ser Tyr Ser Gly Ile Thr Thr Tyr Asn Pro Ser Leu Lys Ser Arg Val Thr Met Leu Arg Asp Thr Ser Lys Asn Gin Phe Ser Leu Arg Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys Ala Arg Ser Leu Ala Arg Thr Thr Ala Met Asp Tyr Trp Gly Gin Gly Ser Leu Val Thr Val Ser Ser Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Ser Gly Gly

204 Gly Gly Ser Asp Thr Gly Arg Pro Phe Val Glu Met Tyr Ser Glu Ile Pro Glu Ile Ile His Met Thr Glu Gly Arg Glu Leu Val Ile Pro Cys Arg Val Thr Ser Pro Asn Ile Thr Val Thr Leu Lys Lys Phe Pro Leu Asp Thr Leu Ile Pro Asp Gly Lys Arg Ile Ile Trp Asp Ser Arg Lys Gly Phe Ile Ile Ser Asn Ala Thr Tyr Lys Glu Ile Gly Leu Leu Thr Cys Glu Ala Thr Val Asn Gly His Leu Tyr Lys Thr Asn Tyr Leu Thr His Arg Gin Thr Asn Thr Ile Ile Asp Val Val Leu Ser Pro Ser His Gly Ile Glu Leu Ser Val Gly Glu Lys Leu Val Leu Asn Cys Thr Ala Arg Thr Glu Leu Asn Val Gly Ile Asp Phe Asn Trp Glu Tyr Pro Ser Ser Lys His Gin His Lys Lys Leu Val Asn Arg Asp Leu Lys Thr Gin Ser Gly Ser Glu Met Lys Lys Phe Leu Ser Thr Leu Thr Ile Asp Gly Val Thr Arg Ser Asp Gin Gly Leu Tyr Thr Cys Ala Ala Ser Ser Gly Leu Met Thr Lys Lys Asn Ser Thr Phe Val Arg Val His Glu Lys Gly

205 Gly Gly Gly Ser Gly Gly Gly Ser Gly Gly Gly Gly Tyr Ser Met Thr Pro Pro Thr Leu Asn Ile Thr Glu Glu Ser His Val Ile Asp Thr Gly Asp Ser Leu Ser Ile Ser Cys Arg Gly Gin His Pro Leu Glu Trp Ala Trp Pro Gly Ala Gin Glu Ala Pro Ala Thr Gly Asp Lys Asp Ser Glu Asp Thr Gly Val Val Arg Asp Cys Glu Gly Thr Asp Ala Arg Pro Tyr Cys Lys Val Leu Leu Leu His Glu Val His Ala Asn Asp Thr Gly Ser Tyr Val Cys Tyr Tyr Lys Tyr Ile Lys Ala Arg Ile Glu Gly Thr Thr Ala Ala Ser Ser Tyr Val Phe Val Arg Asp Phe Glu Gin Pro Phe Ile Asn Lys Pro Asp Thr Leu Leu Val Asn Arg Lys Asp Ala Met Trp Val Pro Cys Leu Val Ser Ile Pro Gly Leu Asn Val Thr Leu Arg Ser Gin Ser Ser Val Leu Trp Pro Asp Gly Gin Glu Val Val Trp Asp Asp Arg Arg Gly Met Leu Val Ser Thr Pro Leu Leu His Asp Ala Leu Tyr Leu Gin Cys Glu Thr Thr Trp Gly Asp Gin Asp Phe Leu Ser Asn Pro Phe Leu Val His Ile Thr Gly Asn Glu Leu Gly Gly Ser Gly Gly Gly Gly

206 Ser Gly Gly Gly Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser

207 Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly <210> 67 <211> 45 <212> DNA
<213> Artificial <220>
<223> Artificial sequence <400> 67 gggggcggtg gcagtggtgg agggggtagc ggaggcgggg ggagt 45 <210> 68 <211> 15 <212> PRT
<213> Artificial <220>
<223> Artificial sequence <400> 68 Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser <210> 69 <211> 48 <212> DNA
<213> Artificial <220>
<223> Artificial sequence <400> 69 ggtggatcag ggggcggagg atccggcggc ggtagcgggg gtggtggt 48 <210> 70 <211> 16 <212> PRT
<213> Artificial <220>
<223> Artificial sequence

208 <400> 70 Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Ser Gly Gly Gly Gly <210> 71 <211> 39 <212> DNA
<213> Artificial <220>
<223> Artificial sequence <400> 71 ggtggcggtg gttcaggtgg gggatcaggc gggggcggt 39 <210> 72 <211> 13 <212> PRT
<213> Artificial <220>
<223> Artificial sequence <400> 72 Gly Gly Gly Gly Ser Gly Gly Gly Ser Gly Gly Gly Gly <210> 73 <211> 121 <212> PRT
<213> Artificial <220>
<223> Artificial sequence <400> 73 Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Ser Val Phe Lys Ile Asn Val Met Ala Trp Tyr Arg Gln Ala Pro Gly Lys Gly Arg Glu Leu Val

209 Ala Gly Ile Ile Ser Gly Gly Ser Thr Ser Tyr Ala Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala Val Tyr Tyr Cys Ala Phe Ile Thr Thr Glu Ser Asp Tyr Asp Leu Gly Arg Arg Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser <210> 74 <211> 711 <212> PRT
<213> Artificial <220>
<223> Artificial sequence <400> 74 Met Pro Leu Leu Leu Leu Leu Pro Leu Leu Trp Ala Gly Ala Leu Ala Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Asp Ile Ser Ser Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile Tyr Tyr Thr Ser Arg Leu His Ser Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Phe Thr Ile Ser Ser Leu Gln Pro

210 Glu Asp Ile Ala Thr Tyr Tyr Cys Gin Gin Gly Asn Thr Leu Pro Tyr Thr Phe Gly Gin Gly Thr Lys Val Glu Ile Lys Arg Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gin Val Gin Leu Gin Glu Ser Gly Pro Gly Leu Val Arg Pro Ser Gin Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Tyr Ser Ile Thr Ser Asp His Ala Trp Ser Trp Val Arg Gin Pro Pro Gly Arg Gly Leu Glu Trp Ile Gly Tyr Ile Ser Tyr Ser Gly Ile Thr Thr Tyr Asn Pro Ser Leu Lys Ser Arg Val Thr Met Leu Arg Asp Thr Ser Lys Asn Gin Phe Ser Leu Arg Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys Ala Arg Ser Leu Ala Arg Thr Thr Ala Met Asp Tyr Trp Gly Gin Gly Ser Leu Val Thr Val Ser Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val

211 Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Gly Gly Ser Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp Thr Gly Arg Pro Phe Val Glu Met Tyr Ser Glu Ile Pro Glu Ile Ile His Met Thr Glu

212 Gly Arg Glu Leu Val Ile Pro Cys Arg Val Thr Ser Pro Asn Ile Thr Val Thr Leu Lys Lys Phe Pro Leu Asp Thr Leu Ile Pro Asp Gly Lys Arg Ile Ile Trp Asp Ser Arg Lys Gly Phe Ile Ile Ser Asn Ala Thr Tyr Lys Glu Ile Gly Leu Leu Thr Cys Glu Ala Thr Val Asn Gly His Leu Tyr Lys Thr Asn Tyr Leu Thr His Arg Gin Thr Asn Thr Ile Ile Asp Val Val Leu Ser Pro Ser His Gly Ile Glu Leu Ser Val Gly Glu Lys Leu Val Leu Asn Cys Thr Ala Arg Thr Glu Leu Asn Val Gly Ile Asp Phe Asn Trp Glu Tyr Pro Ser Ser Lys His Gin His Lys Lys Leu Val Asn Arg Asp Leu Lys Thr Gin Ser Gly Ser Glu Met Lys Lys Phe Leu Ser Thr Leu Thr Ile Asp Gly Val Thr Arg Ser Asp Gin Gly Leu Tyr Thr Cys Ala Ala Ser Ser Gly Leu Met Thr Lys Lys Asn Ser Thr Phe Val Arg Val His Glu Lys <210> 75 <211> 2133 <212> DNA
<213> Artificial <220>

213 <223> Artificial sequence <400> 75 atgccgctct tgctccttct tccattgctc tgggcgggcg cactggccga tatccaaatg 60 acgcaaagtc caagttctct ttcagccagc gtcggagata gagtcactat aacatgccgc 120 gcgagccagg atatatcaag ctaccttaat tggtatcaac aaaaaccggg taaagcgccg 180 aaactcttga tttattatac cagtaggctc cactccggtg taccaagtcg gttcagtggc 240 tccgggagtg gaaccgactt cacatttaca ataagctctt tgcaaccaga ggatattgca 300 acttactatt gccagcaagg caacacgttg ccttacacgt ttggacaggg aacaaaggtt 360 gagataaagc gagggggcgg tggcagtggt ggagggggta gcggaggcgg ggggagtcaa 420 gtccagctcc aagagtccgg accaggcttg gtcagaccta gccagacgct tagcttgaca 480 tgtacggtga gtggctattc aattacatcc gatcatgctt ggagctgggt ccggcaacct 540 ccaggcagag gattggagtg gattggttat atctcttatt ctggtattac cacatataac 600 ccatcactca aaagtcgggt tactatgctg cgggacacct ccaaaaacca attttccctt 660 cggctgtcat cagtgaccgc ggcggataca gcggtgtatt attgtgcgcg cagcttggcc 720 cgcacaactg caatggatta ctggggtcaa ggttctcttg ttactgttag ttcagataaa 780 actcatacgt gtcccccttg tccagcacca gaattgctgg gaggcccctc tgtgtttttg 840 tttcctccca agccaaaaga cacccttatg atcagtcgga ctccagaagt cacgtgcgtt 900 gtggttgatg tgtcacacga ggatccagaa gtgaaattca actggtacgt tgatggcgtt 960 gaggtccata atgcaaaaac caaaccaaga gaagaacaat ataacagcac ataccgggtg 1020 gtctccgttc tgactgtgtt gcaccaggac tggttgaatg gtaaggaata taagtgcaag 1080 gtgtcaaaca aagcgttgcc tgctccgatc gaaaaaacaa tatccaaggc aaaaggtcaa 1140 ccccgcgagc ctcaagtata tactctccct cctagccgcg acgagttgac aaagaaccag 1200 gtttccttga catgtcttgt caaagggttc tacccgtccg atatagctgt tgaatgggaa 1260 agtaatggcc agccggaaaa taattataaa actactccac cggtacttga ctcagatggt 1320 tcattcttcc tttactccaa acttacagtt gacaaatcca ggtggcaaca gggaaatgta 1380 ttttcttgta gtgttatgca cgaggcgctg cacaatcact atacacaaaa aagcctttct 1440 cttagcccag gagggggctc tggaggagga agcggcggag gcggaagcgg agggggaggt 1500 ggctccggag gcggtggcag cgacaccgga cgaccgttcg tagagatgta ctctgaaata 1560

214 ccagagataa tccacatgac tgaaggacgg gagctggtga taccctgcag ggtaacatct 1620 cccaacatta cggtgactct caagaagttc cctcttgata cactgattcc ggatggtaaa 1680 cggatcatat gggatagtcg aaaaggtttt ataatcagca atgcaaccta taaggagatt 1740 gggctcttga cctgcgaagc cactgttaat gggcatcttt ataagacgaa ctatcttacc 1800 catcgccaga caaacaccat tatagatgtg gttttgtccc ctagtcacgg gatagaactc 1860 tcagtgggcg agaagctggt cctcaattgt actgccagga ccgaacttaa tgtgggtatc 1920 gatttcaatt gggaatatcc atcttcaaaa caccaacaca aaaagctcgt taacagggac 1980 ttgaagaccc aatctggatc tgagatgaag aagttccttt ctacattgac aattgacggc 2040 gttacgcgaa gcgaccaagg cttgtatact tgcgcagcgt catccggtct gatgaccaaa 2100 aaaaacagca cttttgtaag agttcacgaa aag 2133 <210> 76 <211> 711 <212> PRT
<213> Artificial <220>
<223> Artificial sequence <400> 76 Met Pro Leu Leu Leu Leu Leu Pro Leu Leu Trp Ala Gly Ala Leu Ala Ser Asp Thr Gly Arg Pro Phe Val Glu Met Tyr Ser Glu Ile Pro Glu Ile Ile His Met Thr Glu Gly Arg Glu Leu Val Ile Pro Cys Arg Val Thr Ser Pro Asn Ile Thr Val Thr Leu Lys Lys Phe Pro Leu Asp Thr Leu Ile Pro Asp Gly Lys Arg Ile Ile Trp Asp Ser Arg Lys Gly Phe Ile Ile Ser Asn Ala Thr Tyr Lys Glu Ile Gly Leu Leu Thr Cys Glu

215 Ala Thr Val Asn Gly His Leu Tyr Lys Thr Asn Tyr Leu Thr His Arg Gln Thr Asn Thr Ile Ile Asp Val Val Leu Ser Pro Ser His Gly Ile Glu Leu Ser Val Gly Glu Lys Leu Val Leu Asn Cys Thr Ala Arg Thr Glu Leu Asn Val Gly Ile Asp Phe Asn Trp Glu Tyr Pro Ser Ser Lys His Gln His Lys Lys Leu Val Asn Arg Asp Leu Lys Thr Gln Ser Gly Ser Glu Met Lys Lys Phe Leu Ser Thr Leu Thr Ile Asp Gly Val Thr Arg Ser Asp Gln Gly Leu Tyr Thr Cys Ala Ala Ser Ser Gly Leu Met Thr Lys Lys Asn Ser Thr Phe Val Arg Val His Glu Lys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val

216 Ser Val Leu Thr Val Leu His Gin Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gin Pro Arg Glu Pro Gin Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gin Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gin Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gin Gin Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gin Lys Ser Leu Ser Leu Ser Pro Gly Gly Gly Ser Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Gly Ser Gly Gly Gly Gly Asp Ile Gin Met Thr Gin Ser Pro Ser Ser Leu Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gin Asp Ile Ser Ser Tyr Leu Asn Trp Tyr Gin Gin Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile Tyr Tyr Thr Ser Arg Leu His Ser Gly Val Pro

217 Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Phe Thr Ile Ser Ser Leu Gin Pro Glu Asp Ile Ala Thr Tyr Tyr Cys Gin Gin Gly Asn Thr Leu Pro Tyr Thr Phe Gly Gin Gly Thr Lys Val Glu Ile Lys Arg Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gin Val Gin Leu Gin Glu Ser Gly Pro Gly Leu Val Arg Pro Ser Gin Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Tyr Ser Ile Thr Ser Asp His Ala Trp Ser Trp Val Arg Gin Pro Pro Gly Arg Gly Leu Glu Trp Ile Gly Tyr Ile Ser Tyr Ser Gly Ile Thr Thr Tyr Asn Pro Ser Leu Lys Ser Arg Val Thr Met Leu Arg Asp Thr Ser Lys Asn Gin Phe Ser Leu Arg Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys Ala Arg Ser Leu Ala Arg Thr Thr Ala Met Asp Tyr Trp Gly Gin Gly Ser Leu Val Thr Val Ser Ser <210> 77 <211> 2133 <212> DNA
<213> Artificial

218 <220>
<223> Artificial sequence <400> 77 atgccgctct tgctccttct tccattgctc tgggcgggcg cactggccag cgacaccgga 60 cgaccgttcg tagagatgta ctctgaaata ccagagataa tccacatgac tgaaggacgg 120 gagctggtga taccctgcag ggtaacatct cccaacatta cggtgactct caagaagttc 180 cctcttgata cactgattcc ggatggtaaa cggatcatat gggatagtcg aaaaggtttt 240 ataatcagca atgcaaccta taaggagatt gggctcttga cctgcgaagc cactgttaat 300 gggcatcttt ataagacgaa ctatcttacc catcgccaga caaacaccat tatagatgtg 360 gttttgtccc ctagtcacgg gatagaactc tcagtgggcg agaagctggt cctcaattgt 420 actgccagga ccgaacttaa tgtgggtatc gatttcaatt gggaatatcc atcttcaaaa 480 caccaacaca aaaagctcgt taacagggac ttgaagaccc aatctggatc tgagatgaag 540 aagttccttt ctacattgac aattgacggc gttacgcgaa gcgaccaagg cttgtatact 600 tgcgcagcgt catccggtct gatgaccaaa aaaaacagca cttttgtaag agttcacgaa 660 aaggataaaa ctcatacgtg tcccccttgt ccagcaccag aattgctggg aggcccctct 720 gtgtttttgt ttcctcccaa gccaaaagac acccttatga tcagtcggac tccagaagtc 780 acgtgcgttg tggttgatgt gtcacacgag gatccagaag tgaaattcaa ctggtacgtt 840 gatggcgttg aggtccataa tgcaaaaacc aaaccaagag aagaacaata taacagcaca 900 taccgggtgg tctccgttct gactgtgttg caccaggact ggttgaatgg taaggaatat 960 aagtgcaagg tgtcaaacaa agcgttgcct gctccgatcg aaaaaacaat atccaaggca 1020 aaaggtcaac cccgcgagcc tcaagtatat actctccctc ctagccgcga cgagttgaca 1080 aagaaccagg tttccttgac atgtcttgtc aaagggttct acccgtccga tatagctgtt 1140 gaatgggaaa gtaatggcca gccggaaaat aattataaaa ctactccacc ggtacttgac 1200 tcagatggtt cattcttcct ttactccaaa cttacagttg acaaatccag gtggcaacag 1260 ggaaatgtat tttcttgtag tgttatgcac gaggcgctgc acaatcacta tacacaaaaa 1320 agcctttctc ttagcccagg agggggctct ggaggaggaa gcggcggagg cggaagcgga 1380 gggggaggtg gctccggagg cggtggcgat atccaaatga cgcaaagtcc aagttctctt 1440 tcagccagcg tcggagatag agtcactata acatgccgcg cgagccagga tatatcaagc 1500

219 taccttaatt ggtatcaaca aaaaccgggt aaagcgccga aactcttgat ttattatacc 1560 agtaggctcc actccggtgt accaagtcgg ttcagtggct ccgggagtgg aaccgacttc 1620 acatttacaa taagctcttt gcaaccagag gatattgcaa cttactattg ccagcaaggc 1680 aacacgttgc cttacacgtt tggacaggga acaaaggttg agataaagcg agggggcggt 1740 ggcagtggtg gagggggtag cggaggcggg gggagtcaag tccagctcca agagtccgga 1800 ccaggcttgg tcagacctag ccagacgctt agcttgacat gtacggtgag tggctattca 1860 attacatccg atcatgcttg gagctgggtc cggcaacctc caggcagagg attggagtgg 1920 attggttata tctcttattc tggtattacc acatataacc catcactcaa aagtcgggtt 1980 actatgctgc gggacacctc caaaaaccaa ttttcccttc ggctgtcatc agtgaccgcg 2040 gcggatacag cggtgtatta ttgtgcgcgc agcttggccc gcacaactgc aatggattac 2100 tggggtcaag gttctcttgt tactgttagt tca 2133 <210> 78 <211> 652 <212> PRT
<213> Artificial <220>
<223> Artificial sequence <400> 78 Ser Asp Thr Gly Arg Pro Phe Val Glu Met Tyr Ser Glu Ile Pro Glu Ile Ile His Met Thr Glu Gly Arg Glu Leu Val Ile Pro Cys Arg Val Thr Ser Pro Asn Ile Thr Val Thr Leu Lys Lys Phe Pro Leu Asp Thr Leu Ile Pro Asp Gly Lys Arg Ile Ile Trp Asp Ser Arg Lys Gly Phe Ile Ile Ser Asn Ala Thr Tyr Lys Glu Ile Gly Leu Leu Thr Cys Glu

220 Ala Thr Val Asn Gly His Leu Tyr Lys Thr Asn Tyr Leu Thr His Arg Gln Thr Asn Thr Ile Ile Asp Val Val Leu Ser Pro Ser His Gly Ile Glu Leu Ser Val Gly Glu Lys Leu Val Leu Asn Cys Thr Ala Arg Thr Glu Leu Asn Val Gly Ile Asp Phe Asn Trp Glu Tyr Pro Ser Ser Lys His Gln His Lys Lys Leu Val Asn Arg Asp Leu Lys Thr Gln Ser Gly Ser Glu Met Lys Lys Phe Leu Ser Thr Leu Thr Ile Asp Gly Val Thr Arg Ser Asp Gln Gly Leu Tyr Thr Cys Ala Ala Ser Ser Gly Leu Met Thr Lys Lys Asn Ser Thr Phe Val Arg Val His Glu Lys Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Arg Pro Ser Gln Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Tyr Ser Ile Thr Ser Asp His Ala Trp Ser Trp Val Arg Gln Pro Pro Gly Arg Gly Leu Glu Trp Ile Gly Tyr Ile Ser Tyr Ser Gly Ile Thr Thr Tyr Asn Pro Ser Leu Lys Ser Arg Val Thr Met Leu Arg Asp Thr Ser Lys Asn Gln Phe Ser Leu Arg Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys Ala Arg Ser

221 Leu Ala Arg Thr Thr Ala Met Asp Tyr Trp Gly Gln Gly Ser Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val

222 Leu Thr Val Leu His Gin Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gin Pro Arg Glu Pro Gin Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gin Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gin Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gin Gin Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gin Lys Ser Leu Ser Leu Ser Pro <210> 79 <211> 1956 <212> DNA
<213> Artificial <220>
<223> Artificial sequence <400> 79 agcgacaccg gcagaccctt cgtggagatg tacagcgaga tccccgagat catccacatg 60 accgagggca gagagctggt gatcccctgc agagtgacca gccccaacat caccgtgacc 120 ctgaagaagt tccccctgga caccctgatc cccgacggca agagaatcat ctgggacagc 180 agaaagggct tcatcatcag caacgccacc tacaaggaga tcggcctgct gacctgcgag 240 gccaccgtga acggccacct gtacaagacc aactacctga cccacagaca gaccaacacc 300

223 tZZ
0Z61 DeD04.34.300 e0;e30;e0; 0334.30;e3; 34434.0Dee0 000eD0e300 4.00eD0e0ee 0981 De004.03DeD 4.30E.E.D0eDe 4.34.3344344 334.3003e0D 34.3e004.30;
0333;3303e 0081 DDE.OeeDe4.3 eeDee0e003 DOE.3000;ee 30e0e0004.0 e004.03303;
eDeODOE.DDD
017L1 ;e4.34.4.300e eeD;004.330 4.33e04.330e 34.00e3Dee0 eeDDe0;e0e 00e000333;
0891 eD333304.33 DeDe4.04.00e DeDDee0e0D 3330e3000e eeDDOeeeDD 4.3;e3Deeee 0Z91 0e031e3333 30e3334.333 OeeeDeeDD; 34.00E.E.304.0 eeDeVe00e eD00;ee04.D
09S1 004.3e00eDD eD04.334.033 E.34.334.030e 34.004.04.033 Eq0DeD0eDe eDeVeD0e0 00ST 0e00030330 eeeDeOeeDD Oixe;e304.0 0e004.03003 e004.03e4.00 ;DeeD440ee 017171 D4.00e04.333 e0ee0DeDDO e04.03e004.0 04.004.0304.E. DeD4.00e033 333e00333;
08E' D1-e01-e34.33 DeDe00eeDD DeeeeDDDDD D;;D;334.4.D 1eD1-DDE.0 000001-OZET ee04.3DeD0e 33304.03DeD 3304.E.DeDeD ;DeeeeDe0; 0443;eeeDD
DOE.0440eee 09Z1 OeeDe00;00 eeDDeDeeD0 eDDDOeeDeD 4.E.E.04.0DeeD 04.3;e3e4.33 e0eDDDeD00 00ZT 04430eD0eD 34.33304.033 e0;004.030e DOE04.3334.3 E.4.34.3e00eD
4.334.0e3e4.3 01711 D4.01-300333 443DeDeD04. 030030e3De 04.3330300e D1Dee004.03 1J1-0801 ODDee03333 4.4.3e4.3e00e ep;004.330; D000;33300 DOeDeD0000 04.34.3DeDOE.
OZOT OeeD34.334.3 DDeD004.333 D3443;003; eD33000eeD DeD0e4.3033 4.334.04.0eDe 096 04.004.330ee 000e330000 4.3e4.4.E.004.e DDOE.DeDDE.0 033300;333 ;e0e33030;
006 De;DE.4.04.0D DODDeDeODD 03304.3e04.0 DOE.4.34.04.3e 0e04.330e44 1eDDee0ee 0178 DOe1De1x0e 0e04.301e3D E.04.0e0eD0e eee04.34.34.3 DDDeeDe;DD
eDDE.44e300 08L eD1DE.4.334.3 ixix;e00D; E.004.E.E.004.D 300e0ee003 333330eDe0 e04.0001-p0e OZL 004.330DeDD e0DOeeDeD; eD0eDe;300 DOE.04.0eDeD 0;e3e04.330 E.04.333e0eD
099 33443300e0 4.004.3e0033 330030e0e0 0e304.30e30 4.00eDOee0e ODE.304.0e0e 009 04.03443DeD OeDeeOee0e EoDe0;e04.3 DOODOE.D0eD D033030;33 eDe4.04.3300 017S OeDDE.030ee OeDDE.04.030 ODE.03;e3De 04.33DeD0e0 4.334.4.0ee0e e0;e0e0DOe 0817 30030e0eDD DeOee04.3De 0e0eDee04.0 04.30ee0eeD eD0e3DeD0e eDOE.D0eDDD
0Z17 DeVe0004.3 eeDDE.03; eD0004.0Dee 04.30e0DDee OeDDODDE.D0 ;Dee04.304.0 09E 04.30ee0e0D 000;030e0; DOE.031e300 DeDDOEODDD 0e0;304.00; 03e03e34.e L99LO/ZZOZNYI3c1 Za6LLTZOZ CPA

aaccactaca cgcagaagag cctctccctg tctccg 1956 <210> 80 <211> 214 <212> PRT
<213> Artificial <220>
<223> Artificial sequence <400> 80 Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Asp Ile Ser Ser Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile Tyr Tyr Thr Ser Arg Leu His Ser Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Phe Thr Ile Ser Ser Leu Gln Pro Glu Asp Ile Ala Thr Tyr Tyr Cys Gln Gln Gly Asn Thr Leu Pro Tyr Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gin Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gin Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys <210> 81 <211> 642 <212> DNA
<213> Artificial <220>
<223> Artificial sequence <400> 81 gacattcaga tgacccagag ccccagcagc ctgagcgcca gcgtgggaga cagagtgacc 60 atcacctgca gagccagcca ggacatctcc agctacctga actggtatca gcagaaaccc 120 ggcaaagccc caaaactgct gatctactac accagtagac tgcacagcgg cgtgcccagc 180 agattctcag gaagcggctc cggaaccgac ttcaccttca ctatcagcag cctgcagccc 240 gaagatattg ctacttacta ctgccagcag gggaacaccc tgccctatac cttcggccag 300 ggcaccaagg tggagatcaa acgtacggtg gctgcaccat ctgtcttcat cttcccgcca 360 tctgatgagc agttgaaatc tggaactgcc tctgttgtgt gcctgctgaa taacttctat 420 cccagagagg ccaaagtaca gtggaaggtg gataacgccc tccaatcggg taactcccag 480 gagagtgtca cagagcagga cagcaaggac agcacctaca gcctcagcag caccctgacg 540 ctgagcaaag cagactacga gaaacacaaa gtctacgcct gcgaagtcac ccatcagggc 600 ctgagttcgc ccgtcacaaa gagcttcaac aggggagagt gt 642 <210> 82 <211> 674 <212> PRT
<213> Artificial <220>

<223> Artificial sequence <400> 82 Ser Asp Thr Gly Arg Pro Phe Val Glu Met Tyr Ser Glu Ile Pro Glu Ile Ile His Met Thr Glu Gly Arg Glu Leu Val Ile Pro Cys Arg Val Thr Ser Pro Asn Ile Thr Val Thr Leu Lys Lys Phe Pro Leu Asp Thr Leu Ile Pro Asp Gly Lys Arg Ile Ile Trp Asp Ser Arg Lys Gly Phe Ile Ile Ser Asn Ala Thr Tyr Lys Glu Ile Gly Leu Leu Thr Cys Glu Ala Thr Val Asn Gly His Leu Tyr Lys Thr Asn Tyr Leu Thr His Arg Gln Thr Asn Thr Ile Ile Asp Val Val Leu Ser Pro Ser His Gly Ile Glu Leu Ser Val Gly Glu Lys Leu Val Leu Asn Cys Thr Ala Arg Thr Glu Leu Asn Val Gly Ile Asp Phe Asn Trp Glu Tyr Pro Ser Ser Lys His Gln His Lys Lys Leu Val Asn Arg Asp Leu Lys Thr Gln Ser Gly Ser Glu Met Lys Lys Phe Leu Ser Thr Leu Thr Ile Asp Gly Val Thr Arg Ser Asp Gln Gly Leu Tyr Thr Cys Ala Ala Ser Ser Gly Leu Met Thr Lys Lys Asn Ser Thr Phe Val Arg Val His Glu Lys Gly Gly Ser Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Gly Ser Gly Gly Gly Gly Gin Val Gin Leu Gin Glu Ser Gly Pro Gly Leu Val Arg Pro Ser Gin Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Tyr Ser Ile Thr Ser Asp His Ala Trp Ser Trp Val Arg Gin Pro Pro Gly Arg Gly Leu Glu Trp Ile Gly Tyr Ile Ser Tyr Ser Gly Ile Thr Thr Tyr Asn Pro Ser Leu Lys Ser Arg Val Thr Met Leu Arg Asp Thr Ser Lys Asn Gin Phe Ser Leu Arg Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys Ala Arg Ser Leu Ala Arg Thr Thr Ala Met Asp Tyr Trp Gly Gin Gly Ser Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gin Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gin Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gin Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gin Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gin Pro Arg Glu Pro Gin Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gin Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gin Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gin Gin Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gin Lys Ser Leu Ser Leu Ser Pro <210> 83 <211> 2022 <212> DNA
<213> Artificial <220>
<223> Artificial sequence <400> 83 agcgacaccg gcagaccctt cgtggagatg tacagcgaga tccccgagat catccacatg 60 accgagggca gagagctggt gatcccctgc agagtgacca gccccaacat caccgtgacc 120 ctgaagaagt tccccctgga caccctgatc cccgacggca agagaatcat ctgggacagc 180 agaaagggct tcatcatcag caacgccacc tacaaggaga tcggcctgct gacctgcgag 240 gccaccgtga acggccacct gtacaagacc aactacctga cccacagaca gaccaacacc 300 atcatcgacg tggtgctgag ccccagccac ggcatcgagc tgagcgtggg cgagaagctg 360 gtgctgaact gcaccgccag aaccgagctg aacgtgggca tcgacttcaa ctgggagtac 420 cccagcagca agcaccagca caagaagctg gtgaacagag acctgaagac ccagagcggc 480 agcgagatga agaagttcct gagcaccctg accatcgacg gcgtgaccag aagcgaccag 540 ggcctgtaca cctgcgccgc cagcagcggc ctgatgacca agaagaacag caccttcgtg 600 agagtgcacg agaagggagg aagcggagga ggaagcgggg gaggaggaag tggaggagga 660 ggagggagcg gaggaggggg acaggtgcag ctgcaggaga gcggccccgg actggtgagg 720 ccttcccaga ccctgagcct gacatgcaca gtgagcggct acagcatcac aagcgaccac 780 gcctggagct gggtgagaca gccccccgga agaggcctgg aatggatcgg atatatctcc 840 tactcaggca ttaccaccta caacccctct ctgaaaagca gagtgaccat gctgagagat 900 actagcaaga accagtttag cctgagactg tctagcgtga ctgccgccga caccgccgtg 960 tactactgcg ccagatccct ggcccggacc acagccatgg attactgggg ccagggaagc 1020 ctggtgacag tgtcctccgc tagcaccaag ggcccatcgg tcttccccct ggcaccctcc 1080 tccaagagca cctctggggg cacagcggcc ctgggctgcc tggtcaagga ctacttcccc 1140 gaaccggtga cggtgtcgtg gaactcaggc gccctgacca gcggcgtgca caccttcccg 1200 gctgtcctac agtcctcagg actctactcc ctcagcagcg tggtgaccgt gccctccagc 1260 agcttgggca cccagaccta catctgcaac gtgaatcaca agcccagcaa caccaaggtg 1320 gacaagaaag ttgagcccaa atcttgtgac aaaactcaca catgcccacc gtgcccagca 1380 cctgaactcc tggggggacc gtcagtcttc ctcttccccc caaaacccaa ggacaccctc 1440 atgatctccc ggacccccga ggtcacatgc gtggtggtgg acgtgagcca cgaagaccct 1500 gaggtcaagt tcaactggta cgtggacggc gtggaggtgc ataatgccaa gacaaagccg 1560 cgggaggagc agtacaacag cacgtaccgt gtggtcagcg tcctcaccgt cctgcaccag 1620 gactggctga atggcaagga gtacaagtgc aaggtctcca acaaagccct cccagccccc 1680 atcgagaaaa ccatctccaa agccaaaggg cagccccgag aaccacaggt gtacaccctg 1740 cccccatccc gggaggagat gaccaagaac caggtcagcc tgacctgcct ggtcaaaggc 1800 ttctatccca gcgacatcgc cgtggagtgg gagagcaatg ggcagccgga gaacaactac 1860 aagaccacgc ctcccgtgct ggactccgac ggctccttct tcctctacag caagctcacc 1920 gtggacaaga gcaggtggca gcaggggaac gtcttctcat gctccgtgat gcatgaggct 1980 ctgcacaacc actacacgca gaagagcctc tccctgtctc cg 2022 <210> 84 <211> 214 <212> PRT
<213> Artificial <220>
<223> Artificial sequence <400> 84 Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Asp Ile Ser Ser Tyr Leu Asn Trp Tyr Gin Gin Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile Tyr Tyr Thr Ser Arg Leu His Ser Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Phe Thr Ile Ser Ser Leu Gin Pro Glu Asp Ile Ala Thr Tyr Tyr Cys Gin Gin Gly Asn Thr Leu Pro Tyr Thr Phe Gly Gin Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gin Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gin Trp Lys Val Asp Asn Ala Leu Gin Ser Gly Asn Ser Gin Glu Ser Val Thr Glu Gin Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gin Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys <210> 85 <211> 642 <212> DNA
<213> Artificial <220>
<223> Artificial sequence <400> 85 gacattcaga tgacccagag ccccagcagc ctgagcgcca gcgtgggaga cagagtgacc 60 atcacctgca gagccagcca ggacatctcc agctacctga actggtatca gcagaaaccc 120 ggcaaagccc caaaactgct gatctactac accagtagac tgcacagcgg cgtgcccagc 180 agattctcag gaagcggctc cggaaccgac ttcaccttca ctatcagcag cctgcagccc 240 gaagatattg ctacttacta ctgccagcag gggaacaccc tgccctatac cttcggccag 300 ggcaccaagg tggagatcaa acgtacggtg gctgcaccat ctgtcttcat cttcccgcca 360 tctgatgagc agttgaaatc tggaactgcc tctgttgtgt gcctgctgaa taacttctat 420 cccagagagg ccaaagtaca gtggaaggtg gataacgccc tccaatcggg taactcccag 480 gagagtgtca cagagcagga cagcaaggac agcacctaca gcctcagcag caccctgacg 540 ctgagcaaag cagactacga gaaacacaaa gtctacgcct gcgaagtcac ccatcagggc 600 ctgagttcgc ccgtcacaaa gagcttcaac aggggagagt gt 642 <210> 86 <211> 676 <212> PRT
<213> Artificial <220>
<223> Artificial sequence <400> 86 Ser Asp Thr Gly Arg Pro Phe Val Glu Met Tyr Ser Glu Ile Pro Glu Ile Ile His Met Thr Glu Gly Arg Glu Leu Val Ile Pro Cys Arg Val Thr Ser Pro Asn Ile Thr Val Thr Leu Lys Lys Phe Pro Leu Asp Thr Leu Ile Pro Asp Gly Lys Arg Ile Ile Trp Asp Ser Arg Lys Gly Phe Ile Ile Ser Asn Ala Thr Tyr Lys Glu Ile Gly Leu Leu Thr Cys Glu Ala Thr Val Asn Gly His Leu Tyr Lys Thr Asn Tyr Leu Thr His Arg Gin Thr Asn Thr Ile Ile Asp Val Val Leu Ser Pro Ser His Gly Ile Glu Leu Ser Val Gly Glu Lys Leu Val Leu Asn Cys Thr Ala Arg Thr Glu Leu Asn Val Gly Ile Asp Phe Asn Trp Glu Tyr Pro Ser Ser Lys His Gin His Lys Lys Leu Val Asn Arg Asp Leu Lys Thr Gin Ser Gly Ser Glu Met Lys Lys Phe Leu Ser Thr Leu Thr Ile Asp Gly Val Thr Arg Ser Asp Gin Gly Leu Tyr Thr Cys Ala Ala Ser Ser Gly Leu Met Thr Lys Lys Asn Ser Thr Phe Val Arg Val His Glu Lys Gly Gly Ser Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Gly Ser Gly Gly Gly Gly Gin Val Gin Leu Gin Glu Ser Gly Pro Gly Leu Val Arg Pro Ser Gin Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Tyr Ser Ile Thr Ser Asp His Ala Trp Ser Trp Val Arg Gin Pro Pro Gly Arg Gly Leu Glu Trp Ile Gly Tyr Ile Ser Tyr Ser Gly Ile Thr Thr Tyr Asn Pro Ser Leu Lys Ser Arg Val Thr Met Leu Arg Asp Thr Ser Lys Asn Gin Phe Ser Leu Arg Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys Ala Arg Ser Leu Ala Arg Thr Thr Ala Met Asp Tyr Trp Gly Gin Gly Ser Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gin Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gin Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys <210> 87 <211> 2028 <212> DNA
<213> Artificial <220>

<223> Artificial sequence <400> 87 agcgacaccg gcagaccctt cgtggagatg tacagcgaga tccccgagat catccacatg 60 accgagggca gagagctggt gatcccctgc agagtgacca gccccaacat caccgtgacc 120 ctgaagaagt tccccctgga caccctgatc cccgacggca agagaatcat ctgggacagc 180 agaaagggct tcatcatcag caacgccacc tacaaggaga tcggcctgct gacctgcgag 240 gccaccgtga acggccacct gtacaagacc aactacctga cccacagaca gaccaacacc 300 atcatcgacg tggtgctgag ccccagccac ggcatcgagc tgagcgtggg cgagaagctg 360 gtgctgaact gcaccgccag aaccgagctg aacgtgggca tcgacttcaa ctgggagtac 420 cccagcagca agcaccagca caagaagctg gtgaacagag acctgaagac ccagagcggc 480 agcgagatga agaagttcct gagcaccctg accatcgacg gcgtgaccag aagcgaccag 540 ggcctgtaca cctgcgccgc cagcagcggc ctgatgacca agaagaacag caccttcgtg 600 agagtgcacg agaagggagg aagcggagga ggaagcgggg gaggaggaag tggaggagga 660 ggagggagcg gaggaggggg acaggtgcag ctgcaggaga gcggccccgg actggtgagg 720 ccttcccaga ccctgagcct gacatgcaca gtgagcggct acagcatcac aagcgaccac 780 gcctggagct gggtgagaca gccccccgga agaggcctgg aatggatcgg atatatctcc 840 tactcaggca ttaccaccta caacccctct ctgaaaagca gagtgaccat gctgagagat 900 actagcaaga accagtttag cctgagactg tctagcgtga ctgccgccga caccgccgtg 960 tactactgcg ccagatccct ggcccggacc acagccatgg attactgggg ccagggaagc 1020 ctggtgacag tgtcctccgc tagcaccaag ggcccatcgg tcttccccct ggcaccctcc 1080 tccaagagca cctctggggg cacagcggcc ctgggctgcc tggtcaagga ctacttcccc 1140 gaaccggtga cggtgtcgtg gaactcaggc gccctgacca gcggcgtgca caccttcccg 1200 gctgtcctac agtcctcagg actctactcc ctcagcagcg tggtgaccgt gccctccagc 1260 agcttgggca cccagaccta catctgcaac gtgaatcaca agcccagcaa caccaaggtg 1320 gacaagaaag ttgagcccaa atcttgtgac aaaactcaca catgcccacc gtgcccagca 1380 cctgaactcc tggggggacc gtcagtcttc ctcttccccc caaaacccaa ggacaccctc 1440 atgatctccc ggacccccga ggtcacatgc gtggtggtgg acgtgagcca cgaagaccct 1500 gaggtcaagt tcaactggta cgtggacggc gtggaggtgc ataatgccaa gacaaagccg 1560 cgggaggagc agtacaacag cacgtaccgt gtggtcagcg tcctcaccgt cctgcaccag 1620 gactggctga atggcaagga gtacaagtgc aaggtctcca acaaagccct cccagccccc 1680 atcgagaaaa ccatctccaa agccaaaggg cagccccgag aaccacaggt gtacaccctg 1740 cccccatccc gggaggagat gaccaagaac caggtcagcc tgacctgcct ggtcaaaggc 1800 ttctatccca gcgacatcgc cgtggagtgg gagagcaatg ggcagccgga gaacaactac 1860 aagaccacgc ctcccgtgct ggactccgac ggctccttct tcctctacag caagctcacc 1920 gtggacaaga gcaggtggca gcaggggaac gtcttctcat gctccgtgat gcatgaggct 1980 ctgcacaacc actacacgca gaagagcctc tccctgtctc cgggtaaa 2028 <210> 88 <211> 214 <212> PRT
<213> Artificial <220>
<223> Artificial sequence <400> 88 Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Asp Ile Ser Ser Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile Tyr Tyr Thr Ser Arg Leu His Ser Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Phe Thr Ile Ser Ser Leu Gln Pro Glu Asp Ile Ala Thr Tyr Tyr Cys Gln Gln Gly Asn Thr Leu Pro Tyr Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gin Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gin Trp Lys Val Asp Asn Ala Leu Gin Ser Gly Asn Ser Gin Glu Ser Val Thr Glu Gin Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gin Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys <210> 89 <211> 642 <212> DNA
<213> Artificial <220>
<223> Artificial sequence <400> 89 gacattcaga tgacccagag ccccagcagc ctgagcgcca gcgtgggaga cagagtgacc 60 atcacctgca gagccagcca ggacatctcc agctacctga actggtatca gcagaaaccc 120 ggcaaagccc caaaactgct gatctactac accagtagac tgcacagcgg cgtgcccagc 180 agattctcag gaagcggctc cggaaccgac ttcaccttca ctatcagcag cctgcagccc 240 gaagatattg ctacttacta ctgccagcag gggaacaccc tgccctatac cttcggccag 300 ggcaccaagg tggagatcaa acgtacggtg gctgcaccat ctgtcttcat cttcccgcca 360 tctgatgagc agttgaaatc tggaactgcc tctgttgtgt gcctgctgaa taacttctat 420 cccagagagg ccaaagtaca gtggaaggtg gataacgccc tccaatcggg taactcccag 480 gagagtgtca cagagcagga cagcaaggac agcacctaca gcctcagcag caccctgacg 540 ctgagcaaag cagactacga gaaacacaaa gtctacgcct gcgaagtcac ccatcagggc 600 ctgagttcgc ccgtcacaaa gagcttcaac aggggagagt gt 642 <210> 90 <211> 675 <212> PRT
<213> Artificial <220>
<223> Artificial sequence <400> 90 Ser Asp Thr Gly Arg Pro Phe Val Glu Met Tyr Ser Glu Ile Pro Glu Ile Ile His Met Thr Glu Gly Arg Glu Leu Val Ile Pro Cys Arg Val Thr Ser Pro Asn Ile Thr Val Thr Leu Lys Lys Phe Pro Leu Asp Thr Leu Ile Pro Asp Gly Lys Arg Ile Ile Trp Asp Ser Arg Lys Gly Phe Ile Ile Ser Asn Ala Thr Tyr Lys Glu Ile Gly Leu Leu Thr Cys Glu Ala Thr Val Asn Gly His Leu Tyr Lys Thr Asn Tyr Leu Thr His Arg Gln Thr Asn Thr Ile Ile Asp Val Val Leu Ser Pro Ser His Gly Ile Glu Leu Ser Val Gly Glu Lys Leu Val Leu Asn Cys Thr Ala Arg Thr Glu Leu Asn Val Gly Ile Asp Phe Asn Trp Glu Tyr Pro Ser Ser Lys His Gin His Lys Lys Leu Val Asn Arg Asp Leu Lys Thr Gin Ser Gly Ser Glu Met Lys Lys Phe Leu Ser Thr Leu Thr Ile Asp Gly Val Thr Arg Ser Asp Gin Gly Leu Tyr Thr Cys Ala Ala Ser Ser Gly Leu Met Thr Lys Lys Asn Ser Thr Phe Val Arg Val His Glu Lys Gly Gly Ser Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Gly Ser Gly Gly Gly Gly Gin Val Gin Leu Gin Glu Ser Gly Pro Gly Leu Val Arg Pro Ser Gin Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Tyr Ser Ile Thr Ser Asp His Ala Trp Ser Trp Val Arg Gin Pro Pro Gly Arg Gly Leu Glu Trp Ile Gly Tyr Ile Ser Tyr Ser Gly Ile Thr Thr Tyr Asn Pro Ser Leu Lys Ser Arg Val Thr Met Leu Arg Asp Thr Ser Lys Asn Gin Phe Ser Leu Arg Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys Ala Arg Ser Leu Ala Arg Thr Thr Ala Met Asp Tyr Trp Gly Gin Gly Ser Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gin Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gin Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gin Gin Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gin Lys Ser Leu Ser Leu Ser Pro Gly <210> 91 <211> 2025 <212> DNA
<213> Artificial <220>
<223> Artificial sequence <400> 91 agcgacaccg gcagaccctt cgtggagatg tacagcgaga tccccgagat catccacatg 60 accgagggca gagagctggt gatcccctgc agagtgacca gccccaacat caccgtgacc 120 ctgaagaagt tccccctgga caccctgatc cccgacggca agagaatcat ctgggacagc 180 agaaagggct tcatcatcag caacgccacc tacaaggaga tcggcctgct gacctgcgag 240 gccaccgtga acggccacct gtacaagacc aactacctga cccacagaca gaccaacacc 300 atcatcgacg tggtgctgag ccccagccac ggcatcgagc tgagcgtggg cgagaagctg 360 gtgctgaact gcaccgccag aaccgagctg aacgtgggca tcgacttcaa ctgggagtac 420 cccagcagca agcaccagca caagaagctg gtgaacagag acctgaagac ccagagcggc 480 agcgagatga agaagttcct gagcaccctg accatcgacg gcgtgaccag aagcgaccag 540 ggcctgtaca cctgcgccgc cagcagcggc ctgatgacca agaagaacag caccttcgtg 600 agagtgcacg agaagggagg aagcggagga ggaagcgggg gaggaggaag tggaggagga 660 ggagggagcg gaggaggggg acaggtgcag ctgcaggaga gcggccccgg actggtgagg 720 ccttcccaga ccctgagcct gacatgcaca gtgagcggct acagcatcac aagcgaccac 780 gcctggagct gggtgagaca gccccccgga agaggcctgg aatggatcgg atatatctcc 840 tactcaggca ttaccaccta caacccctct ctgaaaagca gagtgaccat gctgagagat 900 actagcaaga accagtttag cctgagactg tctagcgtga ctgccgccga caccgccgtg 960 tactactgcg ccagatccct ggcccggacc acagccatgg attactgggg ccagggaagc 1020 ctggtgacag tgtcctccgc tagcaccaag ggcccatcgg tcttccccct ggcaccctcc 1080 tccaagagca cctctggggg cacagcggcc ctgggctgcc tggtcaagga ctacttcccc 1140 gaaccggtga cggtgtcgtg gaactcaggc gccctgacca gcggcgtgca caccttcccg 1200 gctgtcctac agtcctcagg actctactcc ctcagcagcg tggtgaccgt gccctccagc 1260 agcttgggca cccagaccta catctgcaac gtgaatcaca agcccagcaa caccaaggtg 1320 gacaagaaag ttgagcccaa atcttgtgac aaaactcaca catgcccacc gtgcccagca 1380 cctgaactcc tggggggacc gtcagtcttc ctcttccccc caaaacccaa ggacaccctc 1440 atgatctccc ggacccccga ggtcacatgc gtggtggtgg acgtgagcca cgaagaccct 1500 gaggtcaagt tcaactggta cgtggacggc gtggaggtgc ataatgccaa gacaaagccg 1560 cgggaggagc agtacaacag cacgtaccgt gtggtcagcg tcctcaccgt cctgcaccag 1620 gactggctga atggcaagga gtacaagtgc aaggtctcca acaaagccct cccagccccc 1680 atcgagaaaa ccatctccaa agccaaaggg cagccccgag aaccacaggt gtacaccctg 1740 cccccatccc gggaggagat gaccaagaac caggtcagcc tgacctgcct ggtcaaaggc 1800 ttctatccca gcgacatcgc cgtggagtgg gagagcaatg ggcagccgga gaacaactac 1860 aagaccacgc ctcccgtgct ggactccgac ggctccttct tcctctacag caagctcacc 1920 gtggacaaga gcaggtggca gcaggggaac gtcttctcat gctccgtgat gcatgaggct 1980 ctgcacaacc actacacgca gaagagcctc tccctgtctc cgggt 2025 <210> 92 <211> 214 <212> PRT
<213> Artificial <220>
<223> Artificial sequence <400> 92 Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Asp Ile Ser Ser Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile Tyr Tyr Thr Ser Arg Leu His Ser Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Phe Thr Ile Ser Ser Leu Gln Pro Glu Asp Ile Ala Thr Tyr Tyr Cys Gln Gln Gly Asn Thr Leu Pro Tyr Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys <210> 93 <211> 642 <212> DNA
<213> Artificial <220>
<223> Artificial sequence <400> 93 gacattcaga tgacccagag ccccagcagc ctgagcgcca gcgtgggaga cagagtgacc 60 atcacctgca gagccagcca ggacatctcc agctacctga actggtatca gcagaaaccc 120 ggcaaagccc caaaactgct gatctactac accagtagac tgcacagcgg cgtgcccagc 180 agattctcag gaagcggctc cggaaccgac ttcaccttca ctatcagcag cctgcagccc 240 gaagatattg ctacttacta ctgccagcag gggaacaccc tgccctatac cttcggccag 300 ggcaccaagg tggagatcaa acgtacggtg gctgcaccat ctgtcttcat cttcccgcca 360 tctgatgagc agttgaaatc tggaactgcc tctgttgtgt gcctgctgaa taacttctat 420 cccagagagg ccaaagtaca gtggaaggtg gataacgccc tccaatcggg taactcccag 480 gagagtgtca cagagcagga cagcaaggac agcacctaca gcctcagcag caccctgacg 540 ctgagcaaag cagactacga gaaacacaaa gtctacgcct gcgaagtcac ccatcagggc 600 ctgagttcgc ccgtcacaaa gagcttcaac aggggagagt gt 642 <210> 94 <211> 447 <212> PRT
<213> Artificial <220>
<223> Artificial sequence <400> 94 Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Arg Pro Ser Gln Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Tyr Ser Ile Thr Ser Asp His Ala Trp Ser Trp Val Arg Gin Pro Pro Gly Arg Gly Leu Glu Trp Ile Gly Tyr Ile Ser Tyr Ser Gly Ile Thr Thr Tyr Asn Pro Ser Leu Lys Ser Arg Val Thr Met Leu Arg Asp Thr Ser Lys Asn Gin Phe Ser Leu Arg Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys Ala Arg Ser Leu Ala Arg Thr Thr Ala Met Asp Tyr Trp Gly Gin Gly Ser Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gin Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gin Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro <210> 95 <211> 1341 <212> DNA
<213> Artificial <220>
<223> Artificial sequence <400> 95 caggtgcagc tgcaggagag cggccccgga ctggtgaggc cttcccagac cctgagcctg 60 acatgcacag tgagcggcta cagcatcaca agcgaccacg cctggagctg ggtgagacag 120 ccccccggaa gaggcctgga atggatcgga tatatctcct actcaggcat taccacctac 180 aacccctctc tgaaaagcag agtgaccatg ctgagagata ctagcaagaa ccagtttagc 240 ctgagactgt ctagcgtgac tgccgccgac accgccgtgt actactgcgc cagatccctg 300 gcccggacca cagccatgga ttactggggc cagggaagcc tggtgacagt gtcctccgct 360 agcaccaagg gcccatcggt cttccccctg gcaccctcct ccaagagcac ctctgggggc 420 acagcggccc tgggctgcct ggtcaaggac tacttccccg aaccggtgac ggtgtcgtgg 480 aactcaggcg ccctgaccag cggcgtgcac accttcccgg ctgtcctaca gtcctcagga 540 ctctactccc tcagcagcgt ggtgaccgtg ccctccagca gcttgggcac ccagacctac 600 atctgcaacg tgaatcacaa gcccagcaac accaaggtgg acaagaaagt tgagcccaaa 660 tcttgtgaca aaactcacac atgcccaccg tgcccagcac ctgaactcct ggggggaccg 720 tcagtcttcc tcttcccccc aaaacccaag gacaccctca tgatctcccg gacccccgag 780 gtcacatgcg tggtggtgga cgtgagccac gaagaccctg aggtcaagtt caactggtac 840 gtggacggcg tggaggtgca taatgccaag acaaagccgc gggaggagca gtacaacagc 900 acgtaccgtg tggtcagcgt cctcaccgtc ctgcaccagg actggctgaa tggcaaggag 960 tacaagtgca aggtctccaa caaagccctc ccagccccca tcgagaaaac catctccaaa 1020 gccaaagggc agccccgaga accacaggtg tacaccctgc ccccatcccg ggaggagatg 1080 accaagaacc aggtcagcct gacctgcctg gtcaaaggct tctatcccag cgacatcgcc 1140 gtggagtggg agagcaatgg gcagccggag aacaactaca agaccacgcc tcccgtgctg 1200 gactccgacg gctccttctt cctctacagc aagctcaccg tggacaagag caggtggcag 1260 caggggaacg tcttctcatg ctccgtgatg catgaggctc tgcacaacca ctacacgcag 1320 aagagcctct ccctgtctcc g 1341 <210> 96 <211> 419 <212> PRT
<213> Artificial <220>
<223> Artificial sequence <400> 96 Ser Asp Thr Gly Arg Pro Phe Val Glu Met Tyr Ser Glu Ile Pro Glu Ile Ile His Met Thr Glu Gly Arg Glu Leu Val Ile Pro Cys Arg Val Thr Ser Pro Asn Ile Thr Val Thr Leu Lys Lys Phe Pro Leu Asp Thr Leu Ile Pro Asp Gly Lys Arg Ile Ile Trp Asp Ser Arg Lys Gly Phe Ile Ile Ser Asn Ala Thr Tyr Lys Glu Ile Gly Leu Leu Thr Cys Glu Ala Thr Val Asn Gly His Leu Tyr Lys Thr Asn Tyr Leu Thr His Arg Gln Thr Asn Thr Ile Ile Asp Val Val Leu Ser Pro Ser His Gly Ile Glu Leu Ser Val Gly Glu Lys Leu Val Leu Asn Cys Thr Ala Arg Thr Glu Leu Asn Val Gly Ile Asp Phe Asn Trp Glu Tyr Pro Ser Ser Lys His Gln His Lys Lys Leu Val Asn Arg Asp Leu Lys Thr Gln Ser Gly Ser Glu Met Lys Lys Phe Leu Ser Thr Leu Thr Ile Asp Gly Val Thr Arg Ser Asp Gin Gly Leu Tyr Thr Cys Ala Ala Ser Ser Gly Leu Met Thr Lys Lys Asn Ser Thr Phe Val Arg Val His Glu Lys Asp Ile Gin Met Thr Gin Ser Pro Ser Ser Leu Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gin Asp Ile Ser Ser Tyr Leu Asn Trp Tyr Gin Gin Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile Tyr Tyr Thr Ser Arg Leu His Ser Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Phe Thr Ile Ser Ser Leu Gin Pro Glu Asp Ile Ala Thr Tyr Tyr Cys Gin Gin Gly Asn Thr Leu Pro Tyr Thr Phe Gly Gin Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gin Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gin Trp Lys Val Asp Asn Ala Leu Gin Ser Gly Asn Ser Gin Glu Ser Val Thr Glu Gin Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys <210> 97 <211> 1257 <212> DNA
<213> Artificial <220>
<223> Artificial sequence <400> 97 agcgacaccg gcagaccctt cgtggagatg tacagcgaga tccccgagat catccacatg 60 accgagggca gagagctggt gatcccctgc agagtgacca gccccaacat caccgtgacc 120 ctgaagaagt tccccctgga caccctgatc cccgacggca agagaatcat ctgggacagc 180 agaaagggct tcatcatcag caacgccacc tacaaggaga tcggcctgct gacctgcgag 240 gccaccgtga acggccacct gtacaagacc aactacctga cccacagaca gaccaacacc 300 atcatcgacg tggtgctgag ccccagccac ggcatcgagc tgagcgtggg cgagaagctg 360 gtgctgaact gcaccgccag aaccgagctg aacgtgggca tcgacttcaa ctgggagtac 420 cccagcagca agcaccagca caagaagctg gtgaacagag acctgaagac ccagagcggc 480 agcgagatga agaagttcct gagcaccctg accatcgacg gcgtgaccag aagcgaccag 540 ggcctgtaca cctgcgccgc cagcagcggc ctgatgacca agaagaacag caccttcgtg 600 agagtgcacg agaaggacat tcagatgacc cagagcccca gcagcctgag cgccagcgtg 660 ggagacagag tgaccatcac ctgcagagcc agccaggaca tctccagcta cctgaactgg 720 tatcagcaga aacccggcaa agccccaaaa ctgctgatct actacaccag tagactgcac 780 agcggcgtgc ccagcagatt ctcaggaagc ggctccggaa ccgacttcac cttcactatc 840 agcagcctgc agcccgaaga tattgctact tactactgcc agcaggggaa caccctgccc 900 tataccttcg gccagggcac caaggtggag atcaaacgta cggtggctgc accatctgtc 960 ttcatcttcc cgccatctga tgagcagttg aaatctggaa ctgcctctgt tgtgtgcctg 1020 ctgaataact tctatcccag agaggccaaa gtacagtgga aggtggataa cgccctccaa 1080 tcgggtaact cccaggagag tgtcacagag caggacagca aggacagcac ctacagcctc 1140 agcagcaccc tgacgctgag caaagcagac tacgagaaac acaaagtcta cgcctgcgaa 1200 gtcacccatc agggcctgag ttcgcccgtc acaaagagct tcaacagggg agagtgt 1257 <210> 98 <211> 447 <212> PRT
<213> Artificial <220>
<223> Artififcial sequence <400> 98 Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Arg Pro Ser Gln Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Tyr Ser Ile Thr Ser Asp His Ala Trp Ser Trp Val Arg Gln Pro Pro Gly Arg Gly Leu Glu Trp Ile Gly Tyr Ile Ser Tyr Ser Gly Ile Thr Thr Tyr Asn Pro Ser Leu Lys Ser Arg Val Thr Met Leu Arg Asp Thr Ser Lys Asn Gln Phe Ser Leu Arg Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys Ala Arg Ser Leu Ala Arg Thr Thr Ala Met Asp Tyr Trp Gly Gln Gly Ser Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gin Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gin Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gin Gin Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gin Lys Ser Leu Ser Leu Ser Pro <210> 99 <211> 1341 <212> DNA
<213> Artificial <220>
<223> Artificial sequence <400> 99 caggtgcagc tgcaggagag cggccccgga ctggtgaggc cttcccagac cctgagcctg 60 acatgcacag tgagcggcta cagcatcaca agcgaccacg cctggagctg ggtgagacag 120 ccccccggaa gaggcctgga atggatcgga tatatctcct actcaggcat taccacctac 180 aacccctctc tgaaaagcag agtgaccatg ctgagagata ctagcaagaa ccagtttagc 240 ctgagactgt ctagcgtgac tgccgccgac accgccgtgt actactgcgc cagatccctg 300 gcccggacca cagccatgga ttactggggc cagggaagcc tggtgacagt gtcctccgct 360 agcaccaagg gcccatcggt cttccccctg gcaccctcct ccaagagcac ctctgggggc 420 acagcggccc tgggctgcct ggtcaaggac tacttccccg aaccggtgac ggtgtcgtgg 480 aactcaggcg ccctgaccag cggcgtgcac accttcccgg ctgtcctaca gtcctcagga 540 ctctactccc tcagcagcgt ggtgaccgtg ccctccagca gcttgggcac ccagacctac 600 atctgcaacg tgaatcacaa gcccagcaac accaaggtgg acaagaaagt tgagcccaaa 660 tcttgtgaca aaactcacac atgcccaccg tgcccagcac ctgaactcct ggggggaccg 720 tcagtcttcc tcttcccccc aaaacccaag gacaccctca tgatctcccg gacccccgag 780 gtcacatgcg tggtggtgga cgtgagccac gaagaccctg aggtcaagtt caactggtac 840 gtggacggcg tggaggtgca taatgccaag acaaagccgc gggaggagca gtacaacagc 900 acgtaccgtg tggtcagcgt cctcaccgtc ctgcaccagg actggctgaa tggcaaggag 960 tacaagtgca aggtctccaa caaagccctc ccagccccca tcgagaaaac catctccaaa 1020 gccaaagggc agccccgaga accacaggtg tacaccctgc ccccatcccg ggaggagatg 1080 accaagaacc aggtcagcct gacctgcctg gtcaaaggct tctatcccag cgacatcgcc 1140 gtggagtggg agagcaatgg gcagccggag aacaactaca agaccacgcc tcccgtgctg 1200 gactccgacg gctccttctt cctctacagc aagctcaccg tggacaagag caggtggcag 1260 caggggaacg tcttctcatg ctccgtgatg catgaggctc tgcacaacca ctacacgcag 1320 aagagcctct ccctgtctcc g 1341 <210> 100 <211> 441 <212> PRT
<213> Artificial <220>
<223> Artificial sequence <400> 100 Ser Asp Thr Gly Arg Pro Phe Val Glu Met Tyr Ser Glu Ile Pro Glu Ile Ile His Met Thr Glu Gly Arg Glu Leu Val Ile Pro Cys Arg Val Thr Ser Pro Asn Ile Thr Val Thr Leu Lys Lys Phe Pro Leu Asp Thr Leu Ile Pro Asp Gly Lys Arg Ile Ile Trp Asp Ser Arg Lys Gly Phe Ile Ile Ser Asn Ala Thr Tyr Lys Glu Ile Gly Leu Leu Thr Cys Glu Ala Thr Val Asn Gly His Leu Tyr Lys Thr Asn Tyr Leu Thr His Arg Gin Thr Asn Thr Ile Ile Asp Val Val Leu Ser Pro Ser His Gly Ile Glu Leu Ser Val Gly Glu Lys Leu Val Leu Asn Cys Thr Ala Arg Thr Glu Leu Asn Val Gly Ile Asp Phe Asn Trp Glu Tyr Pro Ser Ser Lys His Gin His Lys Lys Leu Val Asn Arg Asp Leu Lys Thr Gin Ser Gly Ser Glu Met Lys Lys Phe Leu Ser Thr Leu Thr Ile Asp Gly Val Thr Arg Ser Asp Gin Gly Leu Tyr Thr Cys Ala Ala Ser Ser Gly Leu Met Thr Lys Lys Asn Ser Thr Phe Val Arg Val His Glu Lys Gly Gly Ser Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Gly Ser Gly Gly Gly Gly Asp Ile Gin Met Thr Gin Ser Pro Ser Ser Leu Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gin Asp Ile Ser Ser Tyr Leu Asn Trp Tyr Gin Gin Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile Tyr Tyr Thr Ser Arg Leu His Ser Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Phe Thr Ile Ser Ser Leu Gin Pro Glu Asp Ile Ala Thr Tyr Tyr Cys Gin Gin Gly Asn Thr Leu Pro Tyr Thr Phe Gly Gin Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gin Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gin Trp Lys Val Asp Asn Ala Leu Gin Ser Gly Asn Ser Gin Glu Ser Val Thr Glu Gin Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gin Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys <210> 101 <211> 1323 <212> DNA
<213> Artificial <220>
<223> Artificial sequence <400> 101 agcgacaccg gcagaccctt cgtggagatg tacagcgaga tccccgagat catccacatg 60 accgagggca gagagctggt gatcccctgc agagtgacca gccccaacat caccgtgacc 120 ctgaagaagt tccccctgga caccctgatc cccgacggca agagaatcat ctgggacagc 180 agaaagggct tcatcatcag caacgccacc tacaaggaga tcggcctgct gacctgcgag 240 gccaccgtga acggccacct gtacaagacc aactacctga cccacagaca gaccaacacc 300 atcatcgacg tggtgctgag ccccagccac ggcatcgagc tgagcgtggg cgagaagctg 360 gtgctgaact gcaccgccag aaccgagctg aacgtgggca tcgacttcaa ctgggagtac 420 cccagcagca agcaccagca caagaagctg gtgaacagag acctgaagac ccagagcggc 480 agcgagatga agaagttcct gagcaccctg accatcgacg gcgtgaccag aagcgaccag 540 ggcctgtaca cctgcgccgc cagcagcggc ctgatgacca agaagaacag caccttcgtg 600 agagtgcacg agaagggagg aagcggagga ggaagcgggg gaggaggaag tggaggagga 660 ggagggagcg gaggaggggg agacattcag atgacccaga gccccagcag cctgagcgcc 720 agcgtgggag acagagtgac catcacctgc agagccagcc aggacatctc cagctacctg 780 aactggtatc agcagaaacc cggcaaagcc ccaaaactgc tgatctacta caccagtaga 840 ctgcacagcg gcgtgcccag cagattctca ggaagcggct ccggaaccga cttcaccttc 900 actatcagca gcctgcagcc cgaagatatt gctacttact actgccagca ggggaacacc 960 ctgccctata ccttcggcca gggcaccaag gtggagatca aacgtacggt ggctgcacca 1020 tctgtcttca tcttcccgcc atctgatgag cagttgaaat ctggaactgc ctctgttgtg 1080 tgcctgctga ataacttcta tcccagagag gccaaagtac agtggaaggt ggataacgcc 1140 ctccaatcgg gtaactccca ggagagtgtc acagagcagg acagcaagga cagcacctac 1200 agcctcagca gcaccctgac gctgagcaaa gcagactacg agaaacacaa agtctacgcc 1260 tgcgaagtca cccatcaggg cctgagttcg cccgtcacaa agagcttcaa caggggagag 1320 tgt 1323 <210> 102 <211> 306 <212> PRT
<213> Homo sapiens <400> 102 Tyr Ser Met Thr Pro Pro Thr Leu Asn Ile Thr Glu Glu Ser His Val Ile Asp Thr Gly Asp Ser Leu Ser Ile Ser Cys Arg Gly Gin His Pro Leu Glu Trp Ala Trp Pro Gly Ala Gin Glu Ala Pro Ala Thr Gly Asp Lys Asp Ser Glu Asp Thr Gly Val Val Arg Asp Cys Glu Gly Thr Asp Ala Arg Pro Tyr Cys Lys Val Leu Leu Leu His Glu Val His Ala Asn Asp Thr Gly Ser Tyr Val Cys Tyr Tyr Lys Tyr Ile Lys Ala Arg Ile Glu Gly Thr Thr Ala Ala Ser Ser Tyr Val Phe Val Arg Asp Phe Glu Gin Pro Phe Ile Asn Lys Pro Asp Thr Leu Leu Val Asn Arg Lys Asp Ala Met Trp Val Pro Cys Leu Val Ser Ile Pro Gly Leu Asn Val Thr Leu Arg Ser Gin Ser Ser Val Leu Trp Pro Asp Gly Gin Glu Val Val Trp Asp Asp Arg Arg Gly Met Leu Val Ser Thr Pro Leu Leu His Asp Ala Leu Tyr Leu Gin Cys Glu Thr Thr Trp Gly Asp Gin Asp Phe Leu Ser Asn Pro Phe Leu Val His Ile Thr Gly Asn Glu Leu Tyr Asp Ile Gin Leu Leu Pro Arg Lys Ser Leu Glu Leu Leu Val Gly Glu Lys Leu Val Leu Asn Cys Thr Val Trp Ala Glu Phe Asn Ser Gly Val Thr Phe Asp Trp Asp Tyr Pro Gly Lys Gin Ala Glu Arg Gly Lys Trp Val Pro Glu Arg Arg Ser Gin Gin Thr His Thr Glu Leu Ser Ser Ile Leu Thr Ile His Asn Val Ser Gin His Asp Leu Gly Ser Tyr Val Cys Lys Ala Asn Asn Gly Ile Gin Arg Phe Arg Glu Ser Thr Glu Val Ile Val His Glu Asn <210> 103 <211> 918 <212> DNA
<213> Homo sapiens <400> 103 tacagcatga cccctcctac cctgaacatc accgaggaga gccacgtgat cgacaccggc 60 gacagcctga gcatcagctg cagaggccag catcctttag agtgggcctg gcccggcgcc 120 caggaggctc ctgccaccgg cgacaaggac agcgaggaca ccggcgtggt gagagactgc 180 gagggcaccg acgccagacc ctactgcaag gtgctgctgc tgcacgaggt gcacgccaac 240 gacaccggca gctacgtgtg ctactacaag tacatcaagg ccagaatcga gggcaccacc 300 gccgccagca gctacgtgtt cgtgagagac ttcgagcagc ccttcatcaa caagcccgac 360 accctgctgg tgaacagaaa ggacgccatg tgggtgccct gcctggtgag catccccggc 420 ctgaacgtga ccctgagaag ccagagcagc gtgctgtggc ccgacggcca ggaggtggtg 480 tgggacgaca gaagaggcat gctggtgagc actcctctgc tgcacgacgc cctgtacctg 540 cagtgcgaga ccacctgggg cgaccaggac ttcctgagca accccttcct ggtgcacatc 600 accggcaacg agctgtacga catccagctg ctgcccagga agagcctgga gctgctggtg 660 ggcgagaagc tggtgctgaa ctgcaccgtg tgggccgagt tcaactccgg cgtgaccttt 720 gactgggact accccggcaa gcaggccgaa aggggaaaat gggtgcccga aagaagaagt 780 cagcagaccc acacagaact gagctccatc ctgacaatcc acaacgtgag ccagcacgac 840 ctgggcagct atgtgtgcaa agctaacaac ggcatccaga gattcagaga gagcaccgag 900 gtgatcgtgc acgaaaat 918 [00292] While specific embodiments of the present invention have been described in the foregoing, it will be appreciated by those skilled in the art that many equivalents, modifications, substitutions, and variations may be made thereto without departing from the spirit and scope of the invention as defined in the appended claims.

Claims

WHAT IS CLAIMED IS:

1. An antibody fusion protein or antigen-binding fragment or domain thereof that are capable of binding substantially to IL-6R and one or more VEGF family members.

2. The antibody fusion protein of claim 1, comprising an antibody against IL-6R or an antigen-biding fragment or domain thereof linked to a VEGF binding unit that comprises an Ig-like domain selected from the group consisting of Ig-like domains of a first VEGF receptor, Ig-like domains of a second VEGF receptor, Ig-like domains of a third VEGF
receptor, and combinations thereof.

3. The antibody fusion protein of claim 1, comprising an antibody against IL-6R or an antigen-biding fragment or domain thereof; wherein at least one of (1) a light chain or antigen-binding fragment or domain thereof, and (2) a heavy chain or antigen-binding fragment or domain thereof is linked to a VEGF binding unit that comprises a plurality of Ig-like domains selected from the group consisting of Ig-like domains of a first VEGF receptor, Ig-like domains of a second VEGF receptor, Ig-like domains of a third VEGF
receptor, and combinations thereof.

4. The antibody fusion protein of claim 3, wherein said IL-6R is human IL-6R.

5. The antibody fusion protein of claim 4; wherein said VEGF binding unit comprises:
(1) (a) Ig-like domain 2, or substantially Ig-like domain 2, of human VEGFR-1;
and (b) Ig-like domain 3, or substantially Ig-like domain 3, of human VEGFR-2; or (2) (a) Ig-like domains 1 and 2, or substantially Ig-like domains 1 and 2, of human VEGFR-3;
or (b) Ig-like domains 2 and 3, or substantially Ig-like domains 2 and 3, of human VEGFR-3;
or (c) Ig-like domains 1, 2 and 3, or substantially Ig-like domains 1, 2, and 3, of human VEGFR-3.

6. The antibody fusion protein of claim 4; wherein a light chain or an antigen-binding fragment or domain thereof and a heavy chain or an antigen-binding fragment or domain thereof of the IL-6R antibody portion is linked to a VEGF binding unit comprising (a) Ig-like domain 2, or substantially Ig-like domain 2, of human VEGFR-1; and (b) Ig-like domain 3, or substantially Ig-like domain 3, of human VEGFR-2.

7. The antibody fusion protein of claim 4; wherein (1) a light chain or an antigen-binding fragment or domain thereof of the IL-6R antibody portion is linked to a first VEGF
binding unit comprising (a) Ig-like domain 2, or substantially Ig-like domain 2, of human VEGFR-1; and (b) Ig-like domain 3, or substantially Ig-like domain 3, of human VEGFR-2;
and (2) a heavy chain or an antigen-binding fragment or domain thereof of the antibody fusion protein is linked to a second VEGF binding unit comprising (a) Ig-like domains 1 and 2, or substantially Ig-like domains 1 and 2, of human VEGFR-3; or (b) Ig-like domains 2 and 3, or substantially Ig-like domains 2 and 3, of human VEGFR-3; or (c) Ig-like domains 1, 2 and 3, or substantially Ig-like domains 1, 2, and 3, of human VEGFR-3.

8. The antibody fusion protein of claim 6; wherein the heavy chain thereof has complementarity determining region HCCDR1, HCCDR2, and HCCDR3 amino acid sequences of SEQ ID NO: 53, 54, and 55.

9. The antibody fusion protein of claim 6; wherein the light chain thereof has complementarity determining region LCCDR1, LCCDR2, and LCCDR3 amino acid sequences of SEQ ID NO: 56, 57, and 58.

10. The antibody fusion protein of claim 6; wherein a pair of heavy chain and light chain thereof has amino acid sequences selected from the group consisting of SEQ ID
NO: 34 and 36, SEQ ID NO: 38 and 40, SEQ ID NO: 42 and 44, SEQ ID NO: 46 and 48, SEQ ID
NO: 78 and 80, SEQ ID NO: 82 and 84, SEQ ID NO: 86 and 88 SEQ ID NO: 90 and 92, SEQ
ID NO:
94 and 96, and SEQ ID NO: 98 and 100.

11. The antibody fusion protein of claim 2, comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 60, SEQ ID NO: 62, SEQ ID NO: 64, SEQ
ID NO:
66, SEQ ID NO: 74, and SEQ ID NO: 76.

12. The antibody fusion protein of claim 2, comprising an amino acid sequence that begins at amino acid 17 of an amino acid sequence selected from the group consisting of SEQ
ID NO: 60, SEQ ID NO: 62, SEQ ID NO: 64, SEQ ID NO: 66, SEQ ID NO: 74, and SEQ
ID
NO: 76.

13. The antibody fusion protein of any one of claims 1-12; wherein said antibody fusion protein binds to IL-6R and a VEGF family member with dissociation constant Kd 10-9M.

14. The antibody fusion protein of any one of claims 1-12; wherein said antibody fusion protein binds to IL-6R and a VEGF family member with dissociation constant Kd

15. An isolated nucleic acid molecule encoding an antibody fusion protein of any of claims 1-12.

16. An isolated nucleic acid molecule having a sequence substantially as listed in SEQ ID
NO: 17, 19, 21, 23, 25, 27, 29, 31, 59, 61, 63, 65, 75, or 77.

17. A vector comprising the nucleic acid molecule of claim 15 or 16.

18. The vector of claim 17, comprising said nucleic molecule operatively linked to an expression control sequence.

19. A host-vector system comprising the expression vector of claim 18 in a host cell.

20. A host-vector system comprising an expression vector pair comprising a pair of nucleic acid sequences selected from the group consisting of: SEQ ID NO: 17 and 19; SEQ
ID NO: 21 and 23; SEQ ID NO: 25 and 27; SEQ ID NO: 29 and 31; SEQ ID NO: 79 and 81;
SEQ ID NO: 83 and 85; SEQ ID NO: 87 and 89; SEQ ID NO: 91 and 93; SEQ ID NO:

and 97; and SEQ ID NO: 99 and 101.

21. A host-vector system comprising an expression vector comprising a nucleic acid sequence selected from the group consisting of: SEQ ID NO: 59, SEQ ID NO: 61, SEQ ID
NO: 63, SEQ ID NO: 65, SEQ ID NO: 75, and SEQ ID NO: 77.

22. A method of producing a substantially purified antibody fusion protein, which method comprises: (a) growing cells of the host-vector system of claim 20 or 21 under conditions permitting production of the antibody fusion protein; and (b) recovering the antibody fusion protein to produce a recovered antibody fusion protein; and (c) purifying said recovered antibody fusion protein to produce the substantially purified antibody fusion protein.

23. A method for treating or controlling at least a disease, condition, or disorder, in a subject in need thereof, which has etiology in aberrant angiogenesis or inflammation; wherein said method comprises administering to said subject an amount of a composition of an antibody fusion protein comprising amino acid sequences substantially as listed in SEQ ID
NO: 34 and 36; SEQ ID NO: 38 and 40; SEQ ID NO: 42 and 44; SEQ ID NO: 46 and 48;
SEQ ID NO: 78 and 80; SEQ ID NO: 82 and 84; SEQ ID NO: 86 and 88; SEQ ID NO:

and 92; SEQ ID NO: 94 and 96; SEQ ID NO: 98 and 100; SEQ ID NO: 60; SEQ ID NO:
62;
SEQ ID NO: 64; SEQ ID NO: 66; SEQ ID NO: 74; or SEQ ID NO: 76.

24. The method of claim 23; wherein said disease, condition, or disorder is selected from the group consisting of: choroidal neovascularization, neovascular age-related macular degeneration, polypoidal choroidal vasculopathy, myopic choroidal neovascularization, vascular leak, macular edema, non-proliferative and proliferative diabetic retinopathy, corneal neovascularization, corneal inflammation, myopic neovascularization, and neovascular glaucoma.

25. The method of claim 24; wherein the subject is administered with a dose of about 25-4000 micrograms of the antibody fusion protein.

26. The method of claim 25; wherein the composition is administered to the subject as an eye drop, a punctal plug, intracameral, retrobulbar, subconjunctival, peribulbar, subtenon, juxta-scleral, trans-scleral, intravitreal, subretinal, or suprachoroidal injection.

27. The method of claim 25; wherein the composition is administered to the subject for a period of at least one month if intraocularly administered.

28. The method of claim 25; wherein the composition is administered to the subject at a frequency of at least once per month if intraocularly administered.

29. A method for treating or controlling at least a systemic disease, condition, or disorder, in a subject in need thereof, which has etiology in aberrant angiogenesis or inflammation;
wherein said method comprises administering to said subject an amount of a composition of an antibody fusion protein or antigen-binding thereof that is capable of binding substantially to IL-6R and one or more VEGF family members.

30. A method for treating or controlling at least a systemic disease, condition, or disorder, in a subject in need thereof, which has etiology in aberrant angiogenesis or inflammation;
wherein said method comprises administering to said subject an amount of a composition of an antibody fusion protein comprising amino acid sequences substantially as listed in SEQ ID
NO: 34 and 36; SEQ ID NO: 38 and 40; SEQ ID NO: 42 and 44; SEQ ID NO: 46 and 48;
SEQ ID NO: 78 and 80; SEQ ID NO: 82 and 84; SEQ ID NO: 86 and 88; SEQ ID NO:

and 92; SEQ ID NO: 94 and 96; SEQ ID NO: 98 and 100; SEQ ID NO: 60; SEQ ID NO:
62;
SEQ ID NO: 64; SEQ ID NO: 66; SEQ ID NO: 74; and SEQ ID NO 76.

31. The method of claim 30; wherein said systemic disease, condition, or disorder involves tumor growth, tumor metastasis, or both.

32. The method of claim 30; wherein said systemic disease, condition, or disorder is atherosclerosis.

33. The method of claim 30; wherein said systemic disease, condition, or disorder is psoriasis.