α4β7 integrin-binding protein and its use

α4β7-binding proteins with defined CDR sequences improve therapeutic efficacy and reduce side effects, enhancing integrin therapy outcomes.

JP2026528931APending Publication Date: 2026-08-26PARAGON THERAPEUTICS INC
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Patent Information

Application Number
JP2026508672
Authority / Receiving Office
JP · JP
Patent Type
Applications
Current Assignee / Owner
Priority Date
2023-08-14
Filing Date
2024-08-14
Publication Date
2026-08-26

AI Technical Summary

Technical Problem

Current integrin therapies, such as α4β7 integrin therapies, are associated with severe side effects and require frequent administrations due to their role in important biological processes.

Method used

Development of α4β7-binding proteins comprising specific heavy and light chain variable regions with defined CDR sequences, offering improved therapeutic efficacy with reduced side effects.

Benefits of technology

The α4β7-binding proteins provide enhanced therapeutic efficacy with reduced side effects, addressing the limitations of existing integrin therapies.

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Abstract

α4β7-binding proteins (e.g., antibodies that bind to α4β7) and their uses are provided herein. In some embodiments, VH comprises a sequence having at least 80% sequence identity to an amino acid sequence following any one of SEQ ID NOs. 1911-1914 and 1925-1927, and VL comprises a sequence having at least 80% sequence identity to an amino acid sequence following any one of SEQ ID NOs. 2017-2020 and 2031-2033.
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Description

Technical Field

[0001] Cross - Reference to Related Applications This application claims the benefit and priority of U.S. Provisional Patent Application No. 63 / 519,483, filed on August 14, 2023, the entire content of which is incorporated herein by reference.

[0002] Sequence Listing This application includes a sequence listing, which is submitted electronically in XML format and the entire content of which is incorporated herein by reference. The XML copy created on August 11, 2024 has a file name of 220703 - 010301_PCT_SL.xml and a size of 1,927,096 bytes.

Background Art

[0003] Background Integrins are cell - adhesion transmembrane receptors that function as extracellular matrix (ECM) - cytoskeleton linkers and transducers of biochemical and mechanical signals between cells and their environment. Due to their exposure on the cell surface and sensitivity to molecular inhibition, integrins such as α4β7 integrin have been investigated as pharmacological targets for treating various diseases, including cancer and inflammatory diseases (e.g., inflammatory bowel disease). However, current integrin therapies are associated with severe side effects and / or require multiple and frequent administrations to maintain therapeutic efficacy, considering the role of integrins in important biological processes. Therefore, improved α4β7 integrin therapies are needed.

Summary of the Invention

Means for Solving the Problems

[0004] Summary In certain embodiments, a) A heavy chain variable region (VH) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 3, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 109, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 215, and a light chain variable region (VL) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 321, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 427, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 533, b) A heavy chain variable region (VH) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 4, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 110, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 216, and a light chain variable region (VL) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 322, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 428, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 534, c) A heavy chain variable region (VH) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 5, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 111, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 217, and a light chain variable region (VL) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 323, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 429, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 535, d) A heavy chain variable region (VH) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 6, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 112, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 218, and a light chain variable region (VL) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 324, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 430, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 536, e) A heavy chain variable region (VH) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 81, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 187, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 293, and a light chain variable region (VL) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 399, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 505, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 611, f) A heavy chain variable region (VH) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 82, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 188, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 294, and a light chain variable region (VL) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 400, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 506, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 612, or g) A heavy chain variable region (VH) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 83, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 189, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 295, and a light chain variable region (VL) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 401, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 507, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 613. α4β7-binding proteins containing the above are described herein.

[0005] In some embodiments, VH includes a sequence having at least 80% sequence identity to an amino acid sequence following any one of sequence numbers 1911-1914 and 1925-1927, and VL includes a sequence having at least 80% sequence identity to an amino acid sequence following any one of sequence numbers 2017-2020 and 2031-2033.

[0006] In some embodiments, VH includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1911, and VL includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2017.

[0007] In some embodiments, VH includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1912, and VL includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2018.

[0008] In some embodiments, VH includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1913, and VL includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2019.

[0009] In some embodiments, VH includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1914, and VL includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2020.

[0010] In some embodiments, VH includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1925, and VL includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2031.

[0011] In some embodiments, VH includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1926, and VL includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2032.

[0012] In some embodiments, VH includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1927, and VL includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2033.

[0013] In a particular embodiment, a) a heavy chain variable region (VH) comprising (i) CDR1 having an amino acid sequence following any one of SEQ ID NOs: 7-26, 32-58, 60-80, and 84-106, (ii) CDR2 having an amino acid sequence following any one of SEQ ID NOs: 113-132, 138-164, 166-186, and 190-212, and (iii) CDR3 having an amino acid sequence following any one of SEQ ID NOs: 219-238, 244-270, 272-292, and 296-318, and b) (i) sequence number This specification describes α4β7-binding proteins comprising a light chain variable region (VL) including (ii) CDR1 having an amino acid sequence following any one of sequence numbers 325-344, 350-376, 378-398, and 402-424, CDR2 having an amino acid sequence following any one of sequence numbers 431-450, 456-482, 484-504, and 508-530, and (iii) CDR3 having an amino acid sequence following any one of sequence numbers 537-556, 562-588, 590-610, and 614-636.

[0014] In some embodiments, the VH includes (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 7, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 113, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 219, and the VL includes (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 325, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 431, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 537.

[0015] In some embodiments, the VH includes (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 8, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 114, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 220, and the VL includes (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 326, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 432, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 538.

[0016] In some embodiments, the VH includes (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 9, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 115, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 221, and the VL includes (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 327, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 433, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 539.

[0017] In some embodiments, the VH includes (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 10, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 116, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 222, and the VL includes (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 328, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 434, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 540.

[0018] In some embodiments, the VH includes (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 11, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 117, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 223, and the VL includes (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 329, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 435, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 541.

[0019] In some embodiments, the VH includes (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 12, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 118, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 224, and the VL includes (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 330, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 436, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 542.

[0020] In some embodiments, the VH includes (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 13, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 119, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 225, and the VL includes (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 331, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 437, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 543.

[0021] In some embodiments, the VH comprises (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 14, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 120, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 226, and the VL comprises (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 332, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 438, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 544.

[0022] In some embodiments, the VH comprises (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 15, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 121, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 227, and the VL comprises (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 333, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 439, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 545.

[0023] In some embodiments, the VH comprises (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 16, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 122, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 228, and the VL comprises (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 334, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 440, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 546.

[0024] In some embodiments, the VH comprises (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 17, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 123, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 229, and the VL comprises (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 335, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 441, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 547.

[0025] In some embodiments, the VH comprises (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 18, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 124, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 230, and the VL comprises (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 336, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 442, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 548.

[0026] In some embodiments, the VH comprises (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 19, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 125, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 231, and the VL comprises (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 337, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 443, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 549.

[0027] In some embodiments, the VH includes (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 20, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 126, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 232, and the VL includes (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 338, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 444, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 550.

[0028] In some embodiments, the VH includes (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 21, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 127, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 233, and the VL includes (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 339, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 445, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 551.

[0029] In some embodiments, the VH includes (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 22, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 128, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 234, and the VL includes (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 340, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 446, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 552.

[0030] In some embodiments, the VH includes (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 23, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 129, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 235, and the VL includes (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 341, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 447, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 553.

[0031] In some embodiments, the VH includes (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 24, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 130, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 236, and the VL includes (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 342, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 448, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 554.

[0032] In some embodiments, the VH includes (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 25, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 131, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 237, and the VL includes (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 343, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 449, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 555.

[0033] In some embodiments, the VH includes (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 26, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 132, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 238, and the VL includes (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 344, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 450, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 556.

[0034] In some embodiments, the VH includes (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 32, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 138, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 244, and the VL includes (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 350, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 456, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 562.

[0035] In some embodiments, the VH includes (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 33, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 139, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 245, and the VL includes (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 351, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 457, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 563.

[0036] In some embodiments, the VH includes (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 34, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 140, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 246, and the VL includes (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 352, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 458, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 564.

[0037] In some embodiments, the VH includes (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 35, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 141, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 247, and the VL includes (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 353, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 459, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 565.

[0038] In some embodiments, the VH includes (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 36, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 142, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 248, and the VL includes (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 354, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 460, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 566.

[0039] In some embodiments, the VH includes (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 37, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 143, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 249, and the VL includes (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 355, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 461, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 567.

[0040] In some embodiments, the VH includes (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 38, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 144, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 250, and the VL includes (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 356, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 462, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 568.

[0041] In some embodiments, the VH includes (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 39, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 145, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 251, and the VL includes (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 357, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 463, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 569.

[0042] In some embodiments, the VH includes (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 40, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 146, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 252, and the VL includes (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 358, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 464, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 570.

[0043] In some embodiments, the VH includes (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 41, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 147, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 253, and the VL includes (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 359, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 465, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 571.

[0044] In some embodiments, the VH includes (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 42, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 148, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 254, and the VL includes (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 360, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 466, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 572.

[0045] In some embodiments, the VH includes (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 43, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 149, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 255, and the VL includes (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 361, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 467, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 573.

[0046] In some embodiments, the VH includes (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 44, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 150, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 256, and the VL includes (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 362, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 468, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 574.

[0047] In some embodiments, the VH includes (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 45, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 151, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 257, and the VL includes (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 363, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 469, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 575.

[0048] In some embodiments, the VH includes (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 46, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 152, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 258, and the VL includes (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 364, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 470, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 576.

[0049] In some embodiments, the VH includes (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 47, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 153, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 259, and the VL includes (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 365, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 471, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 577.

[0050] In some embodiments, the VH includes (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 48, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 154, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 260, and the VL includes (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 366, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 472, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 578.

[0051] In some embodiments, the VH includes (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 49, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 155, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 261, and the VL includes (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 367, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 473, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 579.

[0052] In some embodiments, the VH includes (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 50, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 156, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 262, and the VL includes (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 368, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 474, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 580.

[0053] In some embodiments, the VH includes (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 51, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 157, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 263, and the VL includes (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 369, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 475, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 581.

[0054] In some embodiments, the VH includes (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 52, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 158, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 264, and the VL includes (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 370, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 476, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 582.

[0055] In some embodiments, the VH includes (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 53, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 159, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 265, and the VL includes (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 371, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 477, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 583.

[0056] In some embodiments, the VH includes (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 54, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 160, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 266, and the VL includes (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 372, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 478, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 584.

[0057] In some embodiments, the VH includes (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 55, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 161, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 267, and the VL includes (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 373, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 479, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 585.

[0058] In some embodiments, the VH includes (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 56, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 162, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 268, and the VL includes (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 374, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 480, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 586.

[0059] In some embodiments, the VH includes (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 57, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 163, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 269, and the VL includes (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 375, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 481, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 587.

[0060] In some embodiments, the VH includes (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 58, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 164, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 270, and the VL includes (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 376, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 482, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 588.

[0061] In some embodiments, the VH includes (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 60, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 166, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 272, and the VL includes (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 378, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 484, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 590.

[0062] In some embodiments, the VH includes (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 61, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 167, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 273, and the VL includes (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 379, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 485, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 591.

[0063] In some embodiments, the VH includes (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 62, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 168, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 274, and the VL includes (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 380, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 486, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 592.

[0064] In some embodiments, the VH includes (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 63, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 169, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 275, and the VL includes (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 381, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 487, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 593.

[0065] In some embodiments, the VH includes (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 64, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 170, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 276, and the VL includes (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 382, ​​(ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 488, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 594.

[0066] In some embodiments, the VH includes (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 65, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 171, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 277, and the VL includes (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 383, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 489, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 595.

[0067] In some embodiments, the VH includes (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 66, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 172, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 278, and the VL includes (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 384, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 490, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 596.

[0068] In some embodiments, the VH includes (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 67, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 173, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 279, and the VL includes (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 385, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 491, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 597. In some embodiments, the VH includes (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 68, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 174, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 280, and the VL includes (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 386, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 492, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 598.

[0069] In some embodiments, the VH includes (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 69, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 175, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 281, and the VL includes (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 387, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 493, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 599.

[0070] In some embodiments, the VH includes (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 70, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 176, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 282, and the VL includes (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 388, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 494, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 600.

[0071] In some embodiments, the VH includes (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 71, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 177, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 283, and the VL includes (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 389, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 495, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 601.

[0072] In some embodiments, the VH includes (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 72, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 178, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 284, and the VL includes (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 390, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 496, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 602.

[0073] In some embodiments, the VH includes (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 73, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 179, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 285, and the VL includes (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 391, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 497, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 603.

[0074] In some embodiments, the VH includes (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 74, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 180, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 286, and the VL includes (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 392, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 498, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 604.

[0075] In some embodiments, the VH includes (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 75, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 181, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 287, and the VL includes (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 393, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 499, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 605.

[0076] In some embodiments, the VH includes (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 76, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 182, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 288, and the VL includes (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 394, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 500, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 606.

[0077] In some embodiments, the VH includes (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 77, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 183, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 289, and the VL includes (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 395, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 501, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 607.

[0078] In some embodiments, the VH includes (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 78, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 184, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 290, and the VL includes (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 396, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 502, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 608.

[0079] In some embodiments, the VH includes (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 79, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 185, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 291, and the VL includes (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 397, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 503, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 609.

[0080] In some embodiments, the VH includes (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 80, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 186, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 292, and the VL includes (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 398, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 504, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 610.

[0081] In some embodiments, the VH includes (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 84, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 190, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 296, and the VL includes (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 402, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 508, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 614.

[0082] In some embodiments, the VH includes (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 85, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 191, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 297, and the VL includes (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 403, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 509, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 615.

[0083] In some embodiments, the VH includes (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 86, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 192, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 298, and the VL includes (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 404, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 510, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 616.

[0084] In some embodiments, the VH includes (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 87, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 193, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 299, and the VL includes (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 405, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 511, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 617.

[0085] In some embodiments, the VH includes (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 88, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 194, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 300, and the VL includes (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 406, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 512, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 618.

[0086] In some embodiments, the VH includes (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 89, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 195, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 301, and the VL includes (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 407, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 513, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 619.

[0087] In some embodiments, the VH includes (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 90, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 196, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 302, and the VL includes (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 408, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 514, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 620.

[0088] In some embodiments, the VH includes (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 91, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 197, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 303, and the VL includes (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 409, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 515, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 621.

[0089] In some embodiments, the VH includes (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 92, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 198, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 304, and the VL includes (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 410, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 516, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 622.

[0090] In some embodiments, the VH includes (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 93, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 199, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 305, and the VL includes (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 411, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 517, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 623.

[0091] In some embodiments, the VH includes (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 94, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 200, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 306, and the VL includes (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 412, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 518, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 624.

[0092] In some embodiments, the VH includes (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 95, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 201, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 307, and the VL includes (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 413, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 519, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 625.

[0093] In some embodiments, the VH includes (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 96, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 202, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 308, and the VL includes (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 414, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 520, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 626.

[0094] In some embodiments, the VH includes (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 97, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 203, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 309, and the VL includes (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 415, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 521, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 627.

[0095] In some embodiments, the VH includes (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 98, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 204, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 310, and the VL includes (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 416, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 522, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 628.

[0096] In some embodiments, the VH includes (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 99, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 205, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 311, and the VL includes (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 417, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 523, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 629.

[0097] In some embodiments, the VH includes (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 100, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 206, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 312, and the VL includes (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 418, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 524, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 630.

[0098] In some embodiments, the VH includes (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 101, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 207, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 313, and the VL includes (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 419, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 525, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 631.

[0099] In some embodiments, the VH includes (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 102, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 208, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 314, and the VL includes (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 420, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 526, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 632.

[0100] In some embodiments, the VH includes (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 103, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 209, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 315, and the VL includes (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 421, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 527, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 633.

[0101] In some embodiments, the VH includes (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 104, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 210, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 316, and the VL includes (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 422, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 528, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 634.

[0102] In some embodiments, the VH includes (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 105, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 211, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 317, and the VL includes (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 423, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 529, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 635.

[0103] In some embodiments, the VH includes (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 106, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 212, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 318, and the VL includes (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 424, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 530, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 636.

[0104] In some embodiments, VH includes a sequence having at least 80% sequence identity to an amino acid sequence following any one of sequence numbers 1915-1934, 1940-1966, 1968-1988, and 1992-2014, and VL includes a sequence having at least 80% sequence identity to an amino acid sequence following any one of sequence numbers 2021-2040, 2046-2072, 2074-2094, and 2098-2120.

[0105] In some embodiments, VH includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 127, and VL includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 134.

[0106] In some embodiments, VH includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1915, and VL includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2021.

[0107] In some embodiments, VH includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1916, and VL includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2022.

[0108] In some embodiments, VH includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1917, and VL includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2023.

[0109] In some embodiments, VH includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1918, and VL includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2024.

[0110] In some embodiments, VH includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1919, and VL includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2025.

[0111] In some embodiments, VH includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1920, and VL includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2026.

[0112] In some embodiments, VH includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1921, and VL includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2027.

[0113] In some embodiments, VH includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1922, and VL includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2028.

[0114] In some embodiments, VH includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1923, and VL includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2029.

[0115] In some embodiments, VH includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1924, and VL includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2030.

[0116] In some embodiments, VH includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1925, and VL includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2031.

[0117] In some embodiments, VH includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1926, and VL includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2032.

[0118] In some embodiments, VH includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1927, and VL includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2033.

[0119] In some embodiments, VH includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1928, and VL includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2034.

[0120] In some embodiments, VH includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1929, and VL includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2035.

[0121] In some embodiments, VH includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1930, and VL includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2036.

[0122] In some embodiments, VH includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1931, and VL includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2037.

[0123] In some embodiments, VH includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1932, and VL includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2038.

[0124] In some embodiments, VH includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1933, and VL includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2039.

[0125] In some embodiments, VH includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1934, and VL includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2040.

[0126] In some embodiments, VH includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1940, and VL includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2046.

[0127] In some embodiments, VH includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1941, and VL includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2047.

[0128] In some embodiments, VH includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1942, and VL includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2048.

[0129] In some embodiments, VH includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1943, and VL includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2049.

[0130] In some embodiments, VH includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1944, and VL includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2050.

[0131] In some embodiments, VH includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1945, and VL includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2051.

[0132] In some embodiments, VH includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1946, and VL includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2052.

[0133] In some embodiments, VH includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1947, and VL includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2053.

[0134] In some embodiments, VH includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1948, and VL includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2054.

[0135] In some embodiments, VH includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1949, and VL includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2055.

[0136] In some embodiments, VH includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1950, and VL includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2056.

[0137] In some embodiments, VH includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1951, and VL includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2057.

[0138] In some embodiments, VH includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1952, and VL includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2058.

[0139] In some embodiments, VH includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1953, and VL includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2059.

[0140] In some embodiments, VH includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1954, and VL includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2060.

[0141] In some embodiments, VH includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1955, and VL includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2061.

[0142] In some embodiments, VH includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1956, and VL includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2062.

[0143] In some embodiments, VH includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1957, and VL includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2063.

[0144] In some embodiments, VH includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1958, and VL includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2064.

[0145] In some embodiments, VH includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1959, and VL includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2065.

[0146] In some embodiments, VH includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1960, and VL includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2066.

[0147] In some embodiments, VH includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1961, and VL includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2067.

[0148] In some embodiments, VH includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1962, and VL includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2068.

[0149] In some embodiments, VH includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1963, and VL includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2069.

[0150] In some embodiments, VH includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1964, and VL includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2070.

[0151] In some embodiments, VH includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1965, and VL includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2071.

[0152] In some embodiments, VH includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1966, and VL includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2072.

[0153] In some embodiments, VH includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1968, and VL includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2074.

[0154] In some embodiments, VH includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1969, and VL includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2075.

[0155] In some embodiments, VH includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1970, and VL includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2076.

[0156] In some embodiments, VH includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1971, and VL includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2077.

[0157] In some embodiments, VH includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1972, and VL includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2078.

[0158] In some embodiments, VH includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1973, and VL includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2079.

[0159] In some embodiments, VH includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1974, and VL includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2080.

[0160] In some embodiments, VH includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1975, and VL includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2081.

[0161] In some embodiments, VH includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1976, and VL includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2082.

[0162] In some embodiments, VH includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1977, and VL includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2083.

[0163] In some embodiments, VH includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1978, and VL includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2084.

[0164] In some embodiments, VH includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1979, and VL includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2085.

[0165] In some embodiments, VH includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1980, and VL includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2086.

[0166] In some embodiments, VH includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1981, and VL includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2087.

[0167] In some embodiments, VH includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1982, and VL includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2088.

[0168] In some embodiments, VH includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1983, and VL includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2089.

[0169] In some embodiments, VH includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1984, and VL includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2090.

[0170] In some embodiments, VH includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1985, and VL includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2091.

[0171] In some embodiments, VH includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1986, and VL includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2092.

[0172] In some embodiments, VH includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1987, and VL includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2093.

[0173] In some embodiments, VH includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1992, and VL includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2098.

[0174] In some embodiments, VH includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1993, and VL includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2099.

[0175] In some embodiments, VH includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1994, and VL includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2100.

[0176] In some embodiments, VH includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1995, and VL includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2101.

[0177] In some embodiments, VH includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1996, and VL includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2102.

[0178] In some embodiments, VH includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1997, and VL includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2103.

[0179] In some embodiments, VH includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1998, and VL includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2104.

[0180] In some embodiments, VH includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1999, and VL includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2105.

[0181] In some embodiments, VH includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2000, and VL includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2106.

[0182] In some embodiments, VH includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2001, and VL includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2107.

[0183] In some embodiments, VH includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2002, and VL includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2108.

[0184] In some embodiments, VH includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2003, and VL includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2109.

[0185] In some embodiments, VH includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2004, and VL includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2110.

[0186] In some embodiments, VH includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2005, and VL includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2111.

[0187] In some embodiments, VH includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2006, and VL includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2112.

[0188] In some embodiments, VH includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2007, and VL includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2113.

[0189] In some embodiments, VH includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2008, and VL includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2114.

[0190] In some embodiments, VH includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2009, and VL includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2115.

[0191] In some embodiments, VH includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2010, and VL includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2116.

[0192] In some embodiments, VH includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2011, and VL includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2117.

[0193] In some embodiments, VH includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2012, and VL includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2118.

[0194] In some embodiments, VH includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2013, and VL includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2119.

[0195] In some embodiments, VH includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2014, and VL includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2120.

[0196] In certain embodiments, the α4β7-binding protein described herein comprises a) a heavy chain variable region (VH) containing an amino acid sequence according to any one of SEQ ID NOs. 1909, 1910, 1935-1939, and 1967, and b) a light chain variable region (VL) containing an amino acid sequence according to any one of SEQ ID NOs. 2015, 2016, 2041-2045, and 2073.

[0197] In some embodiments, VH comprises an amino acid sequence according to SEQ ID NO: 1909, and VL comprises an amino acid sequence according to SEQ ID NO: 2015.

[0198] In some embodiments, VH comprises an amino acid sequence according to SEQ ID NO: 1910, and VL comprises an amino acid sequence according to SEQ ID NO: 2016.

[0199] In some embodiments, VH comprises an amino acid sequence according to SEQ ID NO: 1935, and VL comprises an amino acid sequence according to SEQ ID NO: 2041.

[0200] In some embodiments, VH comprises an amino acid sequence according to SEQ ID NO: 1936, and VL comprises an amino acid sequence according to SEQ ID NO: 2042.

[0201] In some embodiments, VH comprises an amino acid sequence according to SEQ ID NO: 1937, and VL comprises an amino acid sequence according to SEQ ID NO: 2043.

[0202] In some embodiments, VH comprises an amino acid sequence according to SEQ ID NO: 1938, and VL comprises an amino acid sequence according to SEQ ID NO: 2044.

[0203] In some embodiments, VH comprises an amino acid sequence according to SEQ ID NO: 1939, and VL comprises an amino acid sequence according to SEQ ID NO: 2045.

[0204] In some embodiments, VH comprises an amino acid sequence according to SEQ ID NO: 1967, and VL comprises an amino acid sequence according to SEQ ID NO: 2073.

[0205] In certain embodiments, the following α4β7-binding proteins are described herein, comprising a) a heavy chain variable region (VH) having (i) an amino acid sequence of CDR1 having one of SEQ ID NOs: 1 to 106, (ii) a CDR2 having an amino acid sequence of one of SEQ ID NOs: 107 to 212, and (iii) a CDR3 having an amino acid sequence of one of SEQ ID NOs: 213 to 318; b) a light chain variable region (VL) having (i) a CDR1 having an amino acid sequence of one of SEQ ID NOs: 319 to 424, (ii) a CDR2 having an amino acid sequence of one of SEQ ID NOs: 425 to 530, and (iii) a CDR3 having an amino acid sequence of one of SEQ ID NOs: 531 to 636; and c) a modified Fc comprising amino acid modifications M252Y, S254T, and T256E (YTE) and / or L234A / G237A (LAGA).

[0206] In certain embodiments, the following are described herein: a) a heavy chain variable region (VH) comprising (i) a CDR1 having an amino acid sequence according to any one of SEQ ID NOs: 1 to 106, (ii) a CDR2 having an amino acid sequence according to any one of SEQ ID NOs: 107 to 212, and (iii) a CDR3 having an amino acid sequence according to any one of SEQ ID NOs: 213 to 318; b) a light chain variable region (VL) comprising (i) a CDR1 having an amino acid sequence according to any one of SEQ ID NOs: 319 to 424, (ii) a CDR2 having an amino acid sequence according to any one of SEQ ID NOs: 425 to 530, and (iii) a CDR3 having an amino acid sequence according to any one of SEQ ID NOs: 531 to 636; and c) an α4β7-binding protein comprising a modified Fc that extends the half-life of the α4β7-binding protein compared to an α4β7-binding protein without the modified Fc.

[0207] In certain embodiments, α4β7-binding proteins are described herein, in which the α4β7-binding protein specifically binds to the α4β7 epitope and comprises an Fc domain including amino acid modifications M252Y, S254T, and T256E(YTE) and / or L234A / G237A(LAGA).

[0208] In some embodiments, Fc is an IgG1 immunoglobulin Fc domain, an IgG2 immunoglobulin Fc domain, or an IgG4 immunoglobulin Fc domain.

[0209] In some embodiments, Fc is the IgG1 immunoglobulin domain.

[0210] In some embodiments, Fc is the IgG2 immunoglobulin domain.

[0211] In some embodiments, Fc is the IgG4 immunoglobulin domain.

[0212] In some embodiments, the α4β7-binding protein is an antibody.

[0213] Aspects of this disclosure relate to compositions comprising the α4β7 binding protein and a pharmaceutically acceptable carrier described herein. Injectable liquid compositions comprising the α4β7 binding protein and a pharmaceutically acceptable carrier described herein are also provided herein.

[0214] Aspects of this disclosure relate to nucleic acids encoding α4β7-binding proteins as described herein. In some embodiments, recombinant host cells comprising nucleic acids encoding α4β7-binding proteins as described herein are provided herein.

[0215] Aspects of this disclosure relate to a method for treating inflammatory bowel disease in a patient requiring treatment for inflammatory bowel disease, comprising the step of subcutaneously or intravenously administering an effective amount of the α4β7-binding protein described herein to the patient. In some embodiments, the inflammatory bowel disease is Crohn's disease or ulcerative colitis. In some embodiments, the inflammatory bowel disease is ulcerative colitis. In some embodiments, the inflammatory bowel disease is Crohn's disease. In some embodiments, the administration of the α4β7-binding protein is subcutaneous. In some embodiments, the administration of the α4β7-binding protein is intravenous.

[0216] Aspects of this disclosure relate to a method for treating an inflammatory disease in a patient requiring treatment of the inflammatory disease, comprising the step of subcutaneously or intravenously administering an effective amount of the α4β7-binding protein described herein to the patient. In some embodiments, the inflammatory disease is hidradenitis suppurativa. In some embodiments, the administration of the α4β7-binding protein is subcutaneous. In some embodiments, the administration of the α4β7-binding protein is intravenous. [Brief explanation of the drawing]

[0217] Brief explanation of the drawing [Figure 1]Figure 1 shows the binding curves for escalating concentrations of anti-α4β7 comparator antibody, control anti-α4 antibody, and exemplary antibodies (antibody 1 and antibody 2) incubated with the RPMI-8866 cell line, which expresses only α4β7 integrin, as determined by flow cytometry analysis. The x-axis represents antibody concentration in nanomolar (nM) units, and the y-axis represents cell binding as mean fluorescence intensity (MFI).

[0218] [Figure 2] Figure 2 shows the binding curves for Ramos cell lines expressing only α4, as determined by flow cytometry analysis, with gradually increasing concentrations of anti-α4β7 comparator antibody, control anti-α4 antibody, and exemplary antibodies, antibody 1 and antibody 2, incubated with these cells. The x-axis represents antibody concentration in nanomolar units (nM), and the y-axis represents cell binding as mean fluorescence intensity (MFI).

[0219] [Figure 3] Figure 3 shows the percentage of adhesion inhibition of HuT-78 cells expressing α4β7 integrin and α4β1-integrin, mixed with gradually increasing concentrations of control antibodies and exemplary antibodies, antibody 1 and antibody 2, on plates coated with MAdCAM-1. The x-axis represents antibody concentration in nanomolars (nM), and the y-axis represents the percentage of adhesion inhibition.

[0220] [Figure 4] Figure 4 shows the percentage of adhesion inhibition of HuT-78 cells expressing α4β7 integrin and α4β1-integrin, mixed with gradually increasing concentrations of a comparator antibody, a control anti-α4 antibody, and exemplary antibodies, antibody 1 and antibody 2, on a plate coated with VCAM-1. The x-axis represents antibody concentration in nanomolars (nM), and the y-axis represents the percentage of adhesion inhibition. [Modes for carrying out the invention]

[0221] Detailed explanation To facilitate understanding of this disclosure, several terms and phrases are defined below.

[0222] As used herein, unless otherwise indicated, the term “antibody” is understood to mean an intact antibody (e.g., an intact monoclonal antibody), or a fragment of an antibody such as an Fc fragment (e.g., an Fc fragment of a monoclonal antibody), or an antigen-binding fragment of an antibody (e.g., an antigen-binding fragment of a monoclonal antibody) (including modified, manipulated, or chemically conjugated intact antibodies, antigen-binding fragments, or Fc fragments). Generally, an antibody is a multimeric protein containing four polypeptide chains. Two of these polypeptide chains are called immunoglobulin heavy chains (H chains), and two of these polypeptide chains are called immunoglobulin light chains (L chains). The immunoglobulin heavy and light chains are linked by interchain disulfide bonds. The immunoglobulin heavy chain is linked by interchain disulfide bonds. The light chain consists of one variable region (VL) and one constant region (CL). The heavy chain consists of one variable region (VH) and at least three constant regions (CH1, CH2, and CH3). The variable region determines the antibody binding specificity. Each variable region contains three hypervariable regions known as complementarity-determining regions (CDRs), adjacent to four relatively conserved regions known as framework regions (FRs). The ranges of the FRs and CDRs are defined (Kabat, EA, et al. (1991) Sequences of Proteins of Immunological Interest, Fifth Edition, USD Department of Health and Human Services, NIH Publication No. 91-3242, and Chothia, C. et al. (1987) J. Mol. Biol. 196:901-917). The three CDRs, designated CDR1, CDR2, and CDR3, contribute to antibody binding specificity. Naturally occurring antibodies are used as starting materials for engineered antibodies such as chimeric antibodies and humanized antibodies. Examples of antibody-based antigen-binding fragments include Fab, Fab', (Fab')2, Fv, single-chain antibodies (e.g., scFv), minibodies, and diabodies.Examples of modified or manipulated antibodies include chimeric antibodies, humanized antibodies, and polyspecific antibodies (e.g., bispecific antibodies). An example of a chemically conjugated antibody is an antibody conjugated to a toxin moiety.

[0223] The terms "variable domain" and "variable region" are used interchangeably and refer to portions of an antibody or immunoglobulin domain that exhibit sequence variability and are involved in determining the specificity and binding affinity of a particular antibody. Variability is not uniformly distributed throughout the antibody's variable domain, but is concentrated within the subdomains of the heavy and light chain variable regions. These subdomains are called "hypervariable regions" or "complementarity-determining regions" (CDRs). The more conserved (i.e., non-hypervariable) portions of the variable domain are called "framework" regions (FRMs or FRs), which provide a scaffold for the six CDRs to form antigen-binding surfaces in three-dimensional space.

[0224] As used herein, the “Fc polypeptide” of dimer Fc refers to one of the two polypeptides that form the dimer Fc domain (i.e., a polypeptide containing the C-terminal constant region of an immunoglobulin heavy chain that can stably self-associate). For example, the Fc polypeptide of dimer IgG Fc contains the IgG CH2 and IgG CH3 constant domain sequences. Fc can be of the IgA, IgD, IgE, IgG, and IgM classes. These classes are also referred to as α, δ, ε, γ, and μ, respectively. Some of these can be further classified into subclasses (isotypes), e.g., IgG1, IgG2, IgG3, IgG4, IgA1, and IgA2.

[0225] The terms “Fc receptor” and “FcR” are used to describe receptors that bind to the Fc region of an antibody. For example, an FcR can be a human FcR in its natural sequence. Generally, FcRs are those that bind to IgG antibodies (gamma receptors) and include the FcγRI, FcγRII, and FcγRIII subclass receptors (including allelic variants and alternative spliced ​​forms of these receptors). The FcγRII receptor includes FcγRIIA ("activating receptor") and FcγRIIB ("inhibiting receptor"), which have similar amino acid sequences that differ primarily in their cytoplasmic domains. Other isotypes of immunoglobulins can also be bound by certain FcRs (see, e.g., Janeway et al., Immuno Biology: the immune system in health and disease, (Elsevier Science Ltd., NY) (4th ed., 1999)). The activating receptor FcγRIIA contains an immunoreceptor-activated tyrosine motif (ITAM) in its cytoplasmic domain. The inhibitory receptor FcγRIIB contains an immunoreceptor-suppressive tyrosine motif (ITIM) in its cytoplasmic domain (see Daeron, Annu. Rev. Immunol. 15:203-234 (1997)). FcRs are outlined in Ravetch and Kinet, Annu. Rev. Immunol. 9:457-92 (1991); Capel et al., Immunomethods 4:25-34 (1994); and de Haas et al., J. Lab. Clin. Med. 126:330-41 (1995). Other FcRs (including those to be identified in the future) are included in the term "FcR" as used herein. This term also includes the neonatal receptor FcRn, which is responsible for the transfer of maternal IgG to the fetus (Guyer et al., J.Immunol. 117:587 (1976); and Kim et al., J.Immunol. 24:249 (1994)).

[0226] The terms “recipient,” “individual,” “subject,” “host,” and “patient” are used interchangeably herein and, in some embodiments, refer to any mammalian subject, particularly human, to whom diagnosis, treatment, or therapy is desired. “Mammal” for treatment purposes refers to any animal classified as a mammal, including humans, livestock and farm animals, as well as laboratory, zoo, athletic, or companion animals (such as dogs, horses, cats, cattle, sheep, goats, pigs, mice, rats, rabbits, guinea pigs, and monkeys). In some embodiments, the mammal is human. None of these terms require the supervision of a medical professional.

[0227] As used herein, the term “effective dose” means the amount of a compound (e.g., a compound of this disclosure) sufficient to obtain a beneficial or desirable result. An effective dose may be administered in one or more doses, applications, or dosages and is not intended to be limited to any particular formulation or route of administration. As used herein, the term “treatment” includes any effect (e.g., relief, reduction, adjustment, ameliorating, or elimination of a condition, disease, or disorder, or improvement of its symptoms).

[0228] As used herein, the term “pharmaceutical composition” refers to a combination of an active agent and a carrier (inactive or active) that makes the composition particularly suitable for use in in vivo or ex vivo diagnostic or therapeutic purposes.

[0229] As used herein, the term “pharmaceutically acceptable carrier” refers to any standard pharmaceutically acceptable carrier (such as phosphate-buffered salt solutions, water, emulsions (e.g., water / oil or oil / water emulsions), and various types of wetting agents). The composition may also contain stabilizers and preservatives. For examples of carriers, stabilizers, and adjuvants, see, for example, Martin, Remington's Pharmaceutical Sciences, 15th Ed., Mack Publ. Co., Easton, PA (1975).

[0230] As used herein, the terms "a" and "an" mean "one or more" and include the plural unless otherwise appropriate to the context.

[0231] Where used herein, all numbers or numerical ranges include the entire set of integers that fall within or encompass the range, and any fractional values ​​or integers that fall within or encompass the range, unless the context clearly indicates otherwise. Thus, for example, a reference to the range of 90-100% includes 91%, 92%, 93%, 94%, 95%, 95%, 96%, 97%, etc., as well as 91.1%, 91.2%, 91.3%, 91.4%, 91.5%, etc., and 92.1%, 92.2%, 92.3%, 92.4%, 92.5%, etc. In another example, references to the range of 1 to 5,000 times include 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20 times, as well as 1.1, 1.2, 1.3, 1.4, 1.5 times, 2.1, 2.2, 2.3, 2.4, 2.5 times, etc.

[0232] When used herein, "approximately" means a number that includes that number and extends from 10% below that number to 10% above that number. "Approximately" means a range that extends from 10% below the lower limit of that range to 10% above the upper limit of that range.

[0233] "Percent (%) identity" refers to the degree to which two sequences (nucleotides or amino acids) have identical residues at the same positions in an alignment. For example, "The amino acid sequence is X% identical to sequence number Y" refers to the % identity of the amino acid sequence to sequence number Y, and further details that X% of the residues in the amino acid sequence are identical to the residues in the sequence disclosed in sequence number Y. Generally, computer programs are used for such calculations. Exemplary programs for comparing and aligning sequence pairs include ALIGN (Myers and Miller, 1988), FASTA (Pearson and Lipman, 1988; Pearson, 1990), and gapped BLAST (Altschul et al., 1997), BLASTP, BLASTN, or GCG (Devereux et al., 1984).

[0234] Throughout the description, where a composition is described as having, including, or comprising, certain components, or where a process and method is described as having, including, or comprising, certain steps, it is intended that there exist compositions of the disclosure that are essentially composed of or consist of the described components, and that there exist processes and methods of the disclosure that are essentially composed of or consist of the described processing steps.

[0235] As a general rule, unless otherwise specified, percentages of compositions are based on weight. Furthermore, if a variable is not defined, its previous definition prevails.

[0236] α4β7 integrin-binding protein α4β7 integrin-binding proteins are provided herein. In some embodiments, the α4β7 integrin-binding protein is an antibody. In certain embodiments, the α4β7 integrin-binding protein contains a modified Fc that extends the half-life of the α4β7-binding protein compared to an α4β7-binding protein that does not contain the modified Fc.

[0237] In certain embodiments, α4β7 integrin-binding proteins are further described herein, which specifically bind to the α4β7 epitope and include an Fc domain comprising amino acid modifications M252Y, S254T, and T256E(YTE) and / or L234A / G237A(LAGA).

[0238] Table 1 provides the amino acid sequences of exemplary CDRs of α4β7 integrin-binding proteins. Table 1. CDR arrangement [Table 1-1] [Table 1-2] [Table 1-3] [Table 1-4] [Table 1-5] [Table 1-6] [Table 1-7] [Table 1-8] [Table 1-9] [Table 1-10] [Table 1-11] [Table 1-12] [Table 1-13] [Table 1-14] [Table 1-15] [Table 1-16] [Table 1-17] [Table 1-18] [Table 1-19] [Table 1-20] [Table 1-21] [Table 1-22] [Table 1-23] [Table 1-24] [Table 1-25] [Table 1-26] [Table 1-27]

[0239] In some embodiments, the α4β7 integrin-binding protein includes a heavy chain variable region comprising CDR1, CDR2, and CDR3, as listed in Table 1.

[0240] In some embodiments, the α4β7 integrin-binding protein includes a light chain variable region comprising CDR1, CDR2, and CDR3, as listed in Table 1.

[0241] In some embodiments, the α4β7 integrin-binding protein includes a heavy chain variable region comprising (a) a CDR1 having an amino acid sequence according to any one of SEQ ID NOs: 1 to 106, (b) a CDR2 having an amino acid sequence according to any one of SEQ ID NOs: 107 to 212, and (c) a CDR3 having an amino acid sequence according to any one of SEQ ID NOs: 213 to 318. In some embodiments, the α4β7 integrin-binding protein includes a light chain variable region comprising (a) a CDR1 having an amino acid sequence according to any one of SEQ ID NOs: 319 to 424, (b) a CDR2 having an amino acid sequence according to any one of SEQ ID NOs: 425 to 530, and (c) a CDR3 having an amino acid sequence according to any one of SEQ ID NOs: 531 to 536.

[0242] In some embodiments, the α4β7 integrin-binding protein includes a heavy chain variable region comprising (a) CDR1 having an amino acid sequence according to any one of SEQ ID NOs. 637-742, (b) CDR2 having an amino acid sequence according to any one of SEQ ID NOs. 743-848, and (c) CDR3 having an amino acid sequence according to any one of SEQ ID NOs. 849-954. In some embodiments, the α4β7 integrin-binding protein includes a light chain variable region comprising (a) CDR1 having an amino acid sequence according to any one of SEQ ID NOs. 955-1060, (b) CDR2 having an amino acid sequence according to any one of SEQ ID NOs. 1061-1166, and (c) CDR3 having an amino acid sequence according to any one of SEQ ID NOs. 1167-1272.

[0243] In some embodiments, the α4β7 integrin-binding protein comprises a heavy chain. In some embodiments, the α4β7 integrin-binding protein comprises a heavy chain variable region comprising (a) a CDR1 having an amino acid sequence according to any one of SEQ ID NOs: 1273 to 1378, (b) a CDR2 having an amino acid sequence according to any one of SEQ ID NOs: 1378 to 1484, and (c) a CDR3 having an amino acid sequence according to any one of SEQ ID NOs: 1485 to 1590. In some embodiments, the α4β7 integrin-binding protein comprises a light chain variable region comprising (a) a CDR1 having an amino acid sequence according to any one of SEQ ID NOs: 1591 to 1696, (b) a CDR2 having an amino acid sequence according to any one of GIS, YIS, FIS, and PIS, and (c) a CDR3 having an amino acid sequence according to any one of SEQ ID NOs: 1803 to 1908.

[0244] Exemplary amino acid sequences of the heavy chain variable region (VH) and the light chain variable region (VL) of the α4β7 integrin-binding protein are provided in Table 2. Table 2. Sequences of the heavy chain variable region (VH) and the light chain variable region (VL) of the α4β7 integrin-binding protein [Table 2-1] [[ID=V11]] [Table {2-2]] [Table 2-3] [Table 2-4] [Table 2-5] [Table 2-6] [Table 2-7] [Table 2-8] [Table 2-9] [Table 2-10] [Table 2-11] [Table 2-12] [Table 2-13] [Table 2-14] [Table 2-15] [Table 2-16]

[0245] In some embodiments, the α4β7 integrin-binding protein includes a heavy chain variable region (VH) containing an amino acid sequence having at least 80% sequence identity, at least 85% identity, at least 90% identity, at least 95% identity, at least 96% identity, at least 97% identity, at least 98% identity, at least 99% identity, or 100% identity with respect to the amino acid sequences listed in Table 2.

[0246] In some embodiments, the α4β7 integrin-binding protein includes a heavy chain variable region (VH) containing at least 60% (e.g., at least 70%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) the same amino acid sequence as the heavy chain variable region (VH) of the α4β7 integrin-binding protein disclosed in Table 2, and a light chain variable region (VL) containing at least 60% (e.g., at least 70%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) the same amino acid sequence as the light chain variable region (VL) of the same α4β7 integrin-binding protein disclosed in Table 2.

[0247] Fc modification This specification describes α4β7 integrin-binding proteins containing a modified Fc region. Unless otherwise specified herein, the numbering of amino acid residues in the Fc region or constant region follows the EU numbering system, also known as the EU index, as described in Kabat et al., Sequences of Proteins of Immunological Interest, 5th Ed., Public Health Service, National Institutes of Health, Bethesda, MD, 1991.

[0248] In some embodiments, the α4β7 integrin-binding protein comprises a modified Fc comprising one or more modifications. In some embodiments, the one or more modifications are located in the Fc derived from IgG1 (e.g., human IgG1 (hIgG1)). In some embodiments, the one or more modifications are located in the Fc derived from IgG4 (e.g., human IgG4 (hIgG4)). In some embodiments, the one or more modifications are located in the Fc derived from IgG2. In some embodiments, the one or more modifications facilitate selective binding to Fc-gamma receptors.

[0249] The amino acid sequences of exemplary Fc sequences are provided in Table 3. Table 3. Fc Sequences [Table 3-1] [Table 3-2] [Table 3-3] [Table 3-4] [Table 3-5] [Table 3-6] [Table 3-7] [Table 3-8] [Table 3-9] [Table 3-10] [Table 3-11] [Table 3-12] [Table 3-13] [Table 3-14] [Table 3-15] [Table 3-16] [Table 3-17]

[0250] In some embodiments, the α4β7 integrin-binding protein comprises Fc, which has an amino acid sequence with terminal lysine compared to any one of SEQ ID NOs: 2121, 2123, 2126-2152, 2162-2164, 2166-2222, and 2226-2232. In some embodiments, the α4β7 integrin-binding protein comprises Fc, which has an amino acid sequence lacking terminal lysine compared to any one of SEQ ID NOs: 2122, 2124, 2125, 2153-2161, 2165, and 2223-2225.

[0251] In some embodiments, the α4β7 integrin-binding protein includes an Fc having one or more modifications to SEQ ID NO: 2121. In some embodiments, the α4β7 integrin-binding protein includes an Fc having one or more modifications to SEQ ID NO: 2122. In some embodiments, the α4β7 integrin-binding protein includes an Fc having one or more modifications to SEQ ID NO: 2123. In some embodiments, the Fc includes an amino acid sequence having at least 80% sequence identity to an amino acid sequence following any one of SEQ ID NOs: 2121-2123. In some embodiments, the Fc includes an amino acid sequence having at least 85% sequence identity to an amino acid sequence following any one of SEQ ID NOs: 2121-2123. In some embodiments, the Fc includes an amino acid sequence having at least 90% sequence identity to an amino acid sequence following any one of SEQ ID NOs: 2121-2123. In some embodiments, Fc includes an amino acid sequence having at least 95% sequence identity with an amino acid sequence following any one of sequence numbers 2121 to 2123. In some embodiments, Fc includes an amino acid sequence having at least 96% sequence identity with an amino acid sequence following any one of sequence numbers 2121 to 2123. In some embodiments, Fc includes an amino acid sequence having at least 97% sequence identity with an amino acid sequence following any one of sequence numbers 2121 to 2123. In some embodiments, Fc includes an amino acid sequence having at least 98% sequence identity with an amino acid sequence following any one of sequence numbers 2121 to 2123. In some embodiments, Fc includes an amino acid sequence having at least 99% sequence identity with an amino acid sequence following any one of sequence numbers 2121 to 2123. In some embodiments, Fc includes an amino acid sequence following any one of sequence numbers 2121 to 2123.

[0252] In some embodiments, one or more modifications in the modified Fc are selected from the group consisting of S298A, E333A, K334A, K326A, F243L, R292P, Y300L, V305I, P396L, F243L, R292P, Y300L, L235V, P396L, F243L, S239D, I332E, A330L, S267E, L328F, D265S, S239E, K326A, A327H, G237F, K326E, G236A, D270L, H268D, S324T, L234F, N325L, V266L, and S267D. In some embodiments, one or more modifications in the modified Fc are selected from the group consisting of S228P, M252Y, S254T, T256E, T256D, T250Q, H285D, T307A, T307Q, T307R, T307W, L309D, Q411H, Q311V, A378V, E380A, M428L, N434A, N434S, N297A, D265A, L234A, L235A, and N434W.

[0253] In some embodiments, the modified Fc includes specific combinations of amino acid substitutions selected from the group consisting of L234A / L235A;V234A / G237A;L235A / G237A / E318A;S228P / L236E;H268Q / V309L / A330S / A331S;C220S / C226S / C229S / P238S;C226S / C229S / E3233P / L235V / L235A;L234F / L235E / P331S;C226S / P230S;L234A / G237A;L234A / L235A / G237A;Q311R / M428L; and L234A / L235A / P329G.

[0254] M428L / N434S(LS);M252Y / S254T / T256E(YTE);T2 50Q / M428L;T307A / E380A / N434A;T256D / T307Q(DQ);T256D / T307W(DW);M2 52Y / T256D(YD);T307Q / Q311V / A378V(QVV);T256D / H285D / T307R / Q311V / A378V(DDRVV);L309D / Q311H / N434S(DHS);S228P / L235E(SPLE);L234A / L23 5A(LALA);M428L / N434A(LA);L234A / G237A(LAGA);L234A / L235A / G237A(LALAGA);L234A / L235A / P329G(LALAPG);N297A / YTE;D265A / YTE;LALA / YTE;LAGA / YTE;LALAGA / YTE;LALAPG / YTE;N297A / LS;D265A / LS;LALA / LS;LAGA / LS;LALAGA / LS;LALAPG / LS;N297A / DHS;D265A / DHS;LALA / DHS;LAGA / DHS;LA LAGA / DHS; LALAPG / DHS; SP / YTE; SPLE / YTE; SP / LS; SPLE / LS; SP / DHS; SPLE / DHS; N297A / LA; D265A / LA; LALA / LA; LAGA / LA; LALAGA / LA; LALAPG / LA; N297A / N434A; D265A / N434A; LALA / N434A; LAGA / N434A; LALAGA / N434A; LALAPG / N434A; N297A / N434W; D265A / N434W; LALA / N434W; LAGA / N434W; LALAGA / N434 W;LALAPG / N434W;N297A / DQ;D265A / DQ;LALA / DQ;LAGA / DQ;LALAGA / DQ;LALAPG / DQ;N297A / DW;D265A / DW;LALA / DW;LAGA / DW;LALAGA / DW;LALAPG / DW;N 297A / YD;D265A / YD;LALA / YD;LAGA / YD;LALAGA / YD;LALAPG / YD;N297A / QVV;D265A / QVV;LALA / QVV;LAGA / QVV;The modified Fc includes specific combinations of amino acid substitutions selected from the group consisting of D265A / DDRVV;LALA / DDRVV;LAGA / DDRVV;LALAGA / DDRVV;LALAPG / DDRVV;SP / Q311R / M428L;SPLE / Q311R / M428L;N297A / Q311R / M428L;D265A / Q311R / M428L;LALA / Q311R / M428L;LAGA / Q311R / M428L;LALAGA / Q311R / M428L; and LALAPG / Q311R / M428L. In some embodiments, the modified Fc includes specific combinations of amino acid substitutions selected from the group consisting of M428L / N434S(LS) and M252Y / S254T / T256E(YTE). In some embodiments, the modified Fc includes the M428L / N434S(LS) (e.g., SEQ ID NOs. 2139, 2156, 2163) modification. In some embodiments, the modified Fc includes the M252Y / S254T / T256E(YTE) (e.g., SEQ ID NOs. 2132, 2153, 2162) modification.

[0255] In some embodiments, the α4β7 integrin-binding proteins described herein include modifications to improve their ability to mediate effector function. Such modifications are known in the art and include afucosylation or manipulation of the affinity of Fc to the activating receptor (primarily FCGR3a) for antibody-dependent cell-mediated cytotoxicity (ADCC) and C1q for complement-dependent cell-mediated cytotoxicity (CDC).

[0256] In some embodiments, the antibodies provided herein contain an Fc domain (e.g., IgG1) with a reduced fucose content at position Asn297 (EU numbering) compared to naturally occurring Fc domains. Such Fc domains are known to have improved ADCC. In some embodiments, such antibodies contain no fucose at position Asn297.

[0257] In some embodiments, the α4β7 integrin-binding proteins described herein include an Fc region having one or more amino acid substitutions that improve ADCC (such as substitutions at one or more of the 298, 333, and 334 positions of the Fc region). In some embodiments, the antibodies provided herein include an Fc region having one or more amino acid substitutions at the 239, 332, and 330 positions.

[0258] In some embodiments, Fc includes an amino acid sequence having at least 80% sequence identity with an amino acid sequence following any one of sequence numbers 2124 to 2232. In some embodiments, Fc includes an amino acid sequence having at least 85% sequence identity with an amino acid sequence following any one of sequence numbers 2124 to 2232. In some embodiments, Fc includes an amino acid sequence having at least 90% sequence identity with an amino acid sequence following any one of sequence numbers 2124 to 2232. In some embodiments, Fc includes an amino acid sequence having at least 95% sequence identity with an amino acid sequence following any one of sequence numbers 2124 to 2232. In some embodiments, Fc includes an amino acid sequence having at least 96% sequence identity with an amino acid sequence following any one of sequence numbers 2124 to 2232. In some embodiments, Fc includes an amino acid sequence having at least 97% sequence identity with an amino acid sequence following any one of sequence numbers 2124 to 2232. In some embodiments, Fc includes an amino acid sequence having at least 98% sequence identity with an amino acid sequence following any one of sequence numbers 2124 to 2232. In some embodiments, Fc includes an amino acid sequence having at least 99% sequence identity with an amino acid sequence following any one of sequence numbers 2124 to 2232. In some embodiments, Fc includes an amino acid sequence following any one of sequence numbers 2124 to 2232.

[0259] In some embodiments, the α4β7 integrin-binding protein described herein includes an Fc region having at least one galactose residue in an oligosaccharide attached to the Fc region. Such antibody variants may have improved CDC function.

[0260] In some embodiments, the α4β7 integrin-binding proteins described herein include one or more changes that improve or decrease C1q binding and / or CDC.

[0261] In certain embodiments, the Fc region contains one or more amino acid substitutions, and these substitutions increase one or more of the antibody half-life, ADCC activity, ADCP activity, or CDC activity compared to an Fc region without one or more substitutions. In certain embodiments, the one or more amino acid substitutions increase the antibody half-life at pH 6.0 compared to an antibody containing a wild-type Fc region. In certain embodiments, the antibody has an increased half-life that is approximately 10,000 times, 1,000 times, 500 times, 100 times, 50 times, 20 times, 10 times, 9 times, 8 times, 7 times, 6 times, 5 times, 4.5 times, 4 times, 3.5 times, 3 times, 2.5 times, 2 times, 1.95 times, 1.9 times, 1.85 times, 1.8 times, 1.75 times, 1.7 times, 1.65 times, 1.6 times, 1.55 times, 1.50 times, 1.45 times, 1.4 times, 1.35 times, 1.3 times, 1.25 times, 1.2 times, 1.15 times, 1.1 times, or 1.05 times longer compared to an antibody containing the wild-type Fc region.

[0262] In certain embodiments, the Fc region includes one or more amino acid substitutions, and these substitutions reduce one or more of the ADCC activity, ADCP activity, or CDC activity compared to an Fc region without one or more substitutions.

[0263] In certain embodiments, the Fc region binds to an Fcγ receptor selected from the group consisting of FcγRI, FcγRIIa, FcγRIIb, FcγRIIc, FcγRIIIa, and FcγRIIIb. In certain embodiments, the Fc region binds to the Fcγ receptor with higher affinity at pH 6.0 compared to an antibody containing a wild-type Fc region.

[0264] In some embodiments, the α4β7 integrin-binding proteins described herein include an extended half-life (i.e., serum half-life). In some embodiments, the α4β7 integrin-binding proteins described herein include a half-life of at least about 14, 28, 42, 56, 70, 84, 96 weeks, or more than 96 weeks. In some embodiments, the α4β7 integrin-binding proteins described herein have half-lives in the range of approximately 14 to 96 days, approximately 14 to 84 days, approximately 14 to 70 days, approximately 14 to 56 days, approximately 14 to 42 days, approximately 14 to 28 days, approximately 28 to 96 days, approximately 28 to 84 days, approximately 28 to 70 days, approximately 28 to 56 days, approximately 28 to 42 days, approximately 42 to 96 days, approximately 42 to 84 days, approximately 42 to 70 days, approximately 42 to 56 days, approximately 56 to 96 days, approximately 56 to 84 days, approximately 56 to 70 days, approximately 70 to 96 days, approximately 70 to 84 days, or approximately 84 to 96 days. In some embodiments, the α4β7 integrin-binding protein described herein has a half-life in the range of about 42 to about 56 days. In some embodiments, the α4β7 integrin-binding protein described herein has a half-life of at least about 50 days. In some embodiments, the α4β7 integrin-binding protein described herein has a half-life of about 50 days. Methods for measuring half-life are known in the art. In some embodiments, the half-life is measured in non-human primates. In some embodiments, the half-life is measured in humans. In some embodiments, the half-life is measured after intravenous administration. In some embodiments, the half-life is measured after subcutaneous administration.

[0265] In some embodiments, the α4β7 integrin-binding protein described herein has a half-life at least 20% longer than that of a comparison antibody. In some embodiments, the comparison antibody contains the same complementarity-determining region and variable region, but contains a different Fc region. In some embodiments, the half-life of the α4β7 integrin-binding protein described herein is at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, or at least 90% longer than that of a comparison antibody. In some embodiments, the half-life of the α4β7 integrin-binding protein described herein is at least 2 times, at least 3 times, at least 4 times, at least 5 times, at least 6 times, at least 7 times, at least 8 times, at least 9 times, or at least 10 times longer than that of a comparison antibody.

[0266] Treatment method In a particular embodiment, a method for treating inflammatory bowel disease in a patient requiring treatment for inflammatory bowel disease, comprising: a) a heavy chain variable region (VH) comprising (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 3, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 109, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 215; and a light chain variable region (VL) comprising (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 321, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 427, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 533. b) A heavy chain variable region (VH) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 4, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 110, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 216, and a light chain variable region (VL) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 322, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 428, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 534, c) A heavy chain variable region (VH) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 5, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 111, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 217, and a light chain variable region (VL) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 323, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 429, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 535, d) A heavy chain variable region (VH) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 6, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 112, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 218, and a light chain variable region (VL) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 324, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 430, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 536, e) A heavy chain variable region (VH) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 81, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 187, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 293, and a light chain variable region (VL) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 399, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 505, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 611, f) A heavy chain variable region (VH) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 82, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 188, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 294, and a light chain variable region (VL) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 400, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 506, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 612, or g) A heavy chain variable region (VH) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 83, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 189, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 295, and a light chain variable region (VL) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 401, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 507, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 613. This specification describes a method comprising the step of subcutaneously or intravenously administering an effective amount of α4β7 integrin-binding protein containing to the patient.

[0267] In a particular embodiment, a method for treating inflammatory bowel disease in a patient requiring treatment for inflammatory bowel disease, comprising a) a heavy chain variable region (VH) including (i) CDR1 having an amino acid sequence following any one of SEQ ID NOs: 7-26, 32-58, 60-80, and 84-106; (ii) CDR2 having an amino acid sequence following any one of SEQ ID NOs: 113-132, 138-164, 166-186, and 190-212; and (iii) CDR3 having an amino acid sequence following any one of SEQ ID NOs: 219-238, 244-270, 272-292, and 296-318; and b) (i) SEQ ID NO: 3 The Specified Method further describes a method comprising subcutaneously or intravenously administering to the patient an effective amount of an α4β7 integrin-binding protein comprising a light chain variable region (VL) including (ii) CDR1 having an amino acid sequence according to any one of 25-344, 350-376, 378-398, and 402-424, CDR2 having an amino acid sequence according to any one of SEQ ID NOs: 431-450, 456-482, 484-504, and 508-530, and (iii) CDR3 having an amino acid sequence according to any one of 537-556, 562-588, 590-610, and 614-636.

[0268] In a particular embodiment, the present invention further describes a method for treating inflammatory bowel disease in a patient requiring treatment for inflammatory bowel disease, comprising the steps of subcutaneously or intravenously administering to the patient an effective amount of α4β7 integrin-binding protein comprising a) a heavy chain variable region (VH) containing an amino acid sequence according to any one of SEQ ID NOs. 1909, 1910, 1935-1939, 1967, and b) a light chain variable region (VL) containing an amino acid sequence according to any one of SEQ ID NOs. 2015, 2016, 2041-2045, 2073.

[0269] In a particular embodiment, a method for treating inflammatory bowel disease in a patient requiring treatment for inflammatory bowel disease, comprising: a) a heavy chain variable region (VH) comprising (i) a CDR1 having an amino acid sequence according to any one of SEQ ID NOs: 1 to 106, (ii) a CDR2 having an amino acid sequence according to any one of SEQ ID NOs: 107 to 212, and (iii) a CDR3 having an amino acid sequence according to any one of SEQ ID NOs: 213 to 318; b) a CDR1 having an amino acid sequence according to any one of SEQ ID NOs: 319 to 424. The method further describes subcutaneously or intravenously administering to the patient an effective amount of the α4β7 integrin-binding protein comprising (ii) a CDR2 having an amino acid sequence according to any one of sequence numbers 425 to 530, (iii) a light chain variable region (VL) having an amino acid sequence according to any one of sequence numbers 531 to 636, and (c) a modified Fc having amino acid modifications M252Y, S254T, and T256E (YTE) and / or L234A / G237A (LAGA).

[0270] In certain embodiments, the present invention further describes a method for treating inflammatory bowel disease in a patient requiring treatment for inflammatory bowel disease, comprising the step of subcutaneously or intravenously administering to the patient an effective amount of α4β7 integrin-binding protein containing a modified Fc that extends the half-life of the α4β7-binding protein compared to an α4β7-binding protein without a modified Fc.

[0271] In certain embodiments, the present invention further describes a method for treating inflammatory bowel disease in a patient requiring treatment for inflammatory bowel disease, comprising the steps of subcutaneously or intravenously administering an effective amount of α4β7 integrin-binding protein to the patient, wherein the α4β7-binding protein specifically binds to an α4β7 epitope and comprises an Fc domain including amino acid modifications M252Y, S254T, and T256E(YTE) and / or L234A / G237A(LAGA).

[0272] In some embodiments, inflammatory bowel disease is Crohn's disease or ulcerative colitis. In some embodiments, inflammatory bowel disease is ulcerative colitis. In some embodiments, inflammatory bowel disease is Crohn's disease.

[0273] In some embodiments, the administration of α4β7 integrin-binding protein is intravenous, intratumoral, intramuscular, subcutaneous, intrafocal, intraintestinal, intracolonic, intrarectal, intrasacral, or intraperitoneal. In some embodiments, the administration of α4β7 integrin-binding protein is via parenteral routes such as intravenous, intramuscular, subcutaneous, intraarterial, or intraperitoneal administration. In some embodiments, the administration of α4β7 integrin-binding protein is intravenous or subcutaneous. In some embodiments, the administration of α4β7 integrin-binding protein is intravenous. In some embodiments, the administration of α4β7 integrin-binding protein is subcutaneous.

[0274] α4β7 integrin-binding protein can be administered at various intervals and in various doses.

[0275] Pharmaceutical composition This disclosure also features pharmaceutical compositions comprising a therapeutically effective amount of the α4β7 integrin-binding protein described herein. The compositions can be formulated for use in various drug delivery systems. One or more physiologically acceptable excipients or carriers may also be included in the composition for appropriate formulation. Suitable formulations for use in this disclosure are found in Remington's Pharmaceutical Sciences, Mack Publishing Company, Philadelphia, Pa., 17th ed., 1985. For a review of drug delivery methods, see, for example, Langer (Science 249:1527-1533, 1990).

[0276] In some embodiments, the pharmaceutical composition may include, for example, formulation materials for modifying, maintaining, or preserving the composition's pH, volumetric osmolality, viscosity, clarity, color, isotonicity, odor, sterility, stability, rate of dissolution or release, or adsorption or penetration.In such embodiments, suitable formulation materials include amino acids (such as glycine, glutamine, asparagine, arginine, or lysine); antibacterial agents; antioxidants (such as ascorbic acid, sodium sulfite, or sodium hydrogen-sulfite); buffers (such as boric acid, bicarbonate, Tris-HCl, citric acid, phosphoric acid, or other organic acid buffers); bulking agents (such as mannitol or glycine); chelating agents (such as ethylenediaminetetraacetic acid (EDTA)); complexing agents (such as caffeine, polyvinylpyrrolidone, beta-cyclodextrin, or hydroxypropyl-beta-cyclodextrin); fillers; monosaccharides; dissaccharides; and other carbohydrates (such as glucose, mannose, or dextrin); proteins (such as serum albumin, gelatin, or immunoglobulin); colorants, flavoring agents, and diluents; emulsifiers; hydrophilic polymers (such as polyvinylpyrrolidone); low molecular weight polypeptides; salt-forming counterions (such as sodium); and preservatives. This includes, but is not limited to, agents (such as benzalkonium chloride, benzoic acid, salicylic acid, thimerosal, phenethyl alcohol, methylparaben, propylparaben, chlorhexidine, sorbic acid, or hydrogen peroxide); solvents (such as glycerin, propylene glycol, or polyethylene glycol); sugar alcohols (such as mannitol or sorbitol); suspending agents; surfactants or wetting agents (such as Pluronic®, PEG, sorbitan esters, polysorbates, e.g., polysorbate 20, polysorbate, Triton, tromethamine, lecithin, cholesterol, trixapol (tyloxapal)); stability enhancers (such as sucrose or sorbitol); tonicity enhancers (such as alkali metal halides, preferably sodium chloride or potassium chloride, mannitol, sorbitol, etc.); delivery vehicles; diluents; additives, and / or pharmaceutical aids (see Remington's Pharmaceutical Sciences, 18th ed. (Mack Publishing Company, 1990)).

[0277] In some embodiments, the pharmaceutical composition does not contain citrate.

[0278] In some embodiments, the pharmaceutical composition may include nanoparticles, such as polymer nanoparticles, liposomes, or micelles.

[0279] In some embodiments, the pharmaceutical composition may include sustained-release or controlled-release formulations. Techniques for formulating sustained-release or controlled-release means such as liposome carriers, bio-erodible microparticles, or porous beads and depot injections are also known to those skilled in the art. Sustained-release preparations may include, for example, molded articles (e.g., films) or porous polymer microparticles or semipermeable polymer matrices in the form of microcapsules. Sustained-release matrices may include polyesters, hydrogels, polylactides, copolymers of L-glutamic acid and gamma-ethyl-L-glutamate, poly(2-hydroxyethyl-methacrylate), ethylene vinyl acetate, or poly-D(-)-3-hydroxybutyrate. The sustained-release composition may also include liposomes, which can be prepared by any of several methods known in the art.

[0280] Pharmaceutical compositions comprising the α4β7 integrin-binding protein disclosed herein can be provided in dosage unit form and can be prepared by any preferred method. The pharmaceutical compositions should be formulated to suit the intended route of administration. Examples of routes of administration are intravenous (IV), intradermal, inhalation, transdermal, topical, transmucosal, intrathecal, and rectal administration. In some embodiments, the α4β7 integrin-binding protein disclosed herein is administered intravenously or subcutaneously. In some embodiments, the α4β7 integrin-binding protein disclosed herein is administered intravenously. In some embodiments, the α4β7 integrin-binding protein disclosed herein is administered subcutaneously.

[0281] Useful formulations can be prepared by methods known in the field of pharmacy. See, for example, Remington's Pharmaceutical Sciences, 18th ed. (Mack Publishing Company, 1990). Suitable formulation components for parenteral administration include sterile diluents (such as water for injection, saline solution, fixative oil, polyethylene glycol, glycerin, propylene glycol, or other synthetic solvents); antimicrobial agents (such as benzyl alcohol or methylparaben); antioxidants (such as ascorbic acid or sodium bisulfite); chelating agents (such as EDTA); buffers (such as acetic acid, citrate, or phosphoric acid); and agents for adjusting tonicity (such as sodium chloride or dextrose). In some embodiments, formulations for parenteral administration do not contain citrates.

[0282] Suitable carriers for intravenous or subcutaneous administration include physiological saline, bacteriostatic water, Cremophor EL® (BASF, Parsippany, NJ), or phosphate-buffered saline (PBS). The carrier must be stable under manufacturing and storage conditions and must be resistant to microorganisms. The carrier may be a solvent or dispersion medium comprising, for example, water, ethanol, polyols (e.g., glycerol, propylene glycol, and liquid polyethylene glycol), or suitable mixtures thereof.

[0283] Intravenous or subcutaneous drug delivery formulations may be contained in syringes, pens, or bags. In some embodiments, the bag is connected to a channel including a tube and / or needle. In some embodiments, the formulation is a lyophilized formulation or a liquid formulation. In some embodiments, the formulation is an injectable liquid formulation. Liquid formulations can be delivered via subcutaneous administration routes using a variety of devices, including on-body injection devices, auto-injector devices, pre-filled syringes, and syringes. Generally, administration time depends on the volume and device and can range from a few seconds to a few minutes.

[0284] These compositions can be sterilized by conventional sterilization techniques or by filter sterilization. The resulting aqueous solutions can be packaged for immediate use, or they can be freeze-dried, and the freeze-dried preparations can be combined with a sterile aqueous carrier before administration.

[0285] A polyol that acts as an isotonic agent and can stabilize the α4β7 integrin-binding protein can also be included in the formulation. The amount of polyol added to the formulation can vary depending on the desired isotonicity of the formulation. In some embodiments, the aqueous formulation is isotonic. The amount of polyol added can also be varied depending on the molecular weight of the polyol. For example, a small amount of monosaccharide (e.g., mannitol) can be added compared to a dissaccharide (e.g., trehalose). In some embodiments, mannitol is the polyol used in the formulation as a tonicity agent.

[0286] Surfactants or surfactants may also be added to the formulation. Exemplary surfactants include nonionic surfactants (such as polysorbates (e.g., polysorbate 20, 80, etc.) or poloxamers (e.g., poloxamer 188), etc.). The amount of surfactant added is such that it reduces aggregation of the formulated antibody and / or minimizes particle formation in the formulation and / or reduces adsorption. In some embodiments, the formulation may contain a surfactant that is a polysorbate. In some embodiments, the formulation may contain the surfactant polysorbate 80 or Tween® 80. Tween® 80 is a term used to describe polyoxyethylene (20) sorbitan monooleate (see Fiedler, Lexikon der Hifsstoffe, Editio Cantor Verlag Aulendorf, 4th ed., 1996).

[0287] In several embodiments, the protein products of this disclosure are formulated as liquid formulations. In some embodiments, the liquid formulations are prepared in combination with a stabilizing level of sugar. In some embodiments, the liquid formulations are prepared in an aqueous carrier. In some embodiments, the stabilizer is added in an amount less than what would result in a viscosity undesirable or unsuitable for intravenous administration. In some embodiments, the sugar is a dicacaryl (e.g., sucrose). In some embodiments, the liquid formulations may also include one or more of buffers, surfactants, and preservatives.

[0288] In some embodiments, the pH of the liquid formulation is set by the addition of a pharmaceutically acceptable acid and / or base. In some embodiments, the pharmaceutically acceptable acid is hydrochloric acid. In some embodiments, the base is sodium hydroxide.

[0289] The aqueous carriers of interest as described herein are pharmaceutically acceptable (safe and non-toxic for administration to humans) and useful for the preparation of liquid formulations. Examples of carriers include sterile water for injection (SWFI), bacteriostatic water for injection (BWFI), pH buffer solutions (e.g., phosphate-buffered saline), sterile saline solution, Ringer's solution, or dextrose solution.

[0290] Preservatives may be added to the formulations herein as needed to reduce bacterial activity. The addition of preservatives can facilitate, for example, the production of multi-use (multiple-dose) formulations.

[0291] α4β7 integrin-binding proteins can be freeze-dried to produce a freeze-dried formulation containing the protein and a freeze-drying protectant. The freeze-drying protectant may be a sugar (e.g., a disaccharide). In some embodiments, the freeze-drying protectant is sucrose or maltose. The freeze-drying formulation may also contain one or more buffers, surfactants, fillers, and / or preservatives.

[0292] The amount of sucrose or maltose useful for stabilizing lyophilized pharmaceuticals may be at least a 1:2 weight ratio of protein to sucrose or maltose. In some embodiments, the weight ratio of protein to sucrose or maltose is 1:2 to 1:5. In some embodiments, the pH of the formulation before lyophilization is set by the addition of a pharmaceutically acceptable acid and / or base. In some embodiments, the pharmaceutically acceptable acid is hydrochloric acid. In some embodiments, the pharmaceutically acceptable base is sodium hydroxide.

[0293] In some embodiments, the α4β7 integrin-binding protein is administered in a uniform dose. Alternatively, the patient's dose may be adjusted to match the patient's approximate body weight or surface area. Other factors determining the appropriate dosage may include the disease or condition to be treated or prevented, the severity of the disease, the route of administration, as well as the patient's age, sex, and medical condition. Those skilled in the art will routinely further refine the calculations necessary to determine the appropriate dosage for treatment, taking into account the dosage information and assays disclosed herein in particular. The dosage can also be determined using known assays for dosage determination in conjunction with appropriate dose-response data. Individual patient dosages can be adjusted while monitoring disease progression. Blood levels of the targetable construct or complex in the patient can be measured to determine whether the dosage needs to be adjusted to achieve or maintain an effective concentration. Pharmacogenic genomics can be used to determine which targetable constructs and / or complexes, as well as their dosages, are most likely to be effective for a given individual (Schmitz et al., Clinica Chimica Acta 308:43-53, 2001; Steimer et al., Clinica Chimica Acta 308:33-41, 2001).

[0294] Preparation method The above-described α4β7 integrin-binding proteins can be prepared using recombinant DNA techniques well known to those skilled in the art. For example, one or more isolated polynucleotides encoding an α4β7 integrin-binding protein can be ligated with other suitable nucleotide sequences (including, for example, constant region coding sequences and expression regulatory sequences) to produce a conventional gene expression construct (i.e., an expression vector) encoding the desired α4β7 integrin-binding protein. The production of the defined gene construct is within the realm of routine art in this field.

[0295] A nucleic acid encoding a desired α4β7 integrin-binding protein can be incorporated (ligated) into an expression vector, which can then be introduced into host cells by conventional transfection or transformation techniques. Exemplary host cells include Escherichia coli cells, Chinese hamster ovary (CHO) cells, human fetal kidney 293 (HEK293) cells, HeLa cells, baby hamster kidney (BHK) cells, monkey kidney cells (COS), human hepatocellular carcinoma cells (e.g., Hep G2), and other myeloma cells that do not produce IgG proteins. Transformed host cells can be grown under conditions that enable the host cells to express the gene encoding the α4β7 integrin-binding protein.

[0296] Specific expression and purification conditions will vary depending on the expression system used. For example, when expressing a gene in E. coli, the gene is first cloned into an expression vector by placing the engineered gene downstream of a suitable bacterial promoter (e.g., Trp or Tac) and a prokaryotic signal sequence. The expressed protein may be secreted. The expressed protein may accumulate in refractile bodies or inclusion bodies and can be recovered after cell disruption by French press or sonication. The refractile bodies can then be solubilized, and the protein can be refolded and / or cleaved by methods known in the art.

[0297] When expressing a manipulated gene in a eukaryotic host cell (e.g., a CHO cell), the gene is first inserted into an expression vector containing a suitable eukaryotic promoter, a secretory signal, a poly(A) sequence, and a stop codon. Optionally, the vector or gene construct may include enhancers and introns. In embodiments involving a fusion protein containing an α4β7 integrin-binding protein or a portion thereof, the expression vector optionally includes sequences encoding all or part of a constant region capable of expressing all or part of the heavy or light chain. The gene construct can be introduced into a eukaryotic host cell using conventional techniques.

[0298] In some embodiments, an N-terminal signal sequence is included in the protein construct to express an α4β7 integrin-binding protein. Exemplary N-terminal signal sequences include signal sequences derived from interleukin-2, CD-5, IgG kappa light chain, trypsinogen, serum albumin, and prolactin.

[0299] After transfection, single clones for cell bank generation can be isolated using limiting dilution, ELISA, FACS, microscopy, or other methods known in the field, such as Clonepix. The clones can then be cultured under conditions suitable for bioreactor scale-up and maintained for α4β7 integrin-binding protein expression.

[0300] α4β7 integrin-binding proteins can be isolated and purified using methods known in the art (including centrifugation, deep filtration, cell lysis, homogenization, freeze-thaw cycles, affinity purification, gel filtration, ion exchange chromatography, hydrophobic interaction ion exchange chromatography, and mixed-mode chromatography).

[0301] Specific Embodiments Non-limiting specific embodiments are described below, each of which is deemed to fall within the scope of this disclosure. Embodiment 1. The following: a) A heavy chain variable region (VH) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 3, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 109, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 215, and a light chain variable region (VL) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 321, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 427, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 533, b) A heavy chain variable region (VH) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 4, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 110, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 216, and a light chain variable region (VL) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 322, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 428, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 534, c) A heavy chain variable region (VH) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 5, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 111, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 217, and a light chain variable region (VL) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 323, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 429, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 535, d) A heavy chain variable region (VH) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 6, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 112, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 218, and a light chain variable region (VL) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 324, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 430, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 536, e) A heavy chain variable region (VH) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 81, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 187, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 293, and a light chain variable region (VL) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 399, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 505, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 611, f) A heavy chain variable region (VH) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 82, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 188, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 294, and a light chain variable region (VL) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 400, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 506, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 612, or g) A heavy chain variable region (VH) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 83, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 189, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 295, and a light chain variable region (VL) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 401, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 507, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 613. An α4β7 binding protein containing this protein. Embodiment 2. The α4β7 binding protein according to Embodiment 1, wherein VH contains a sequence having at least 80% sequence identity with any one of the amino acid sequences among sequence numbers 1911-1914 and 1925-1927, and VL contains a sequence having at least 80% sequence identity with any one of the amino acid sequences among sequence numbers 2017-2020 and 2031-2033. Embodiment 3. The α4β7 binding protein according to Embodiment 2, wherein VH contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1911, and VL contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2017. Embodiment 4. The α4β7 binding protein according to Embodiment 2, wherein VH contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1912, and VL contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2018. Embodiment 5. The α4β7 binding protein according to Embodiment 2, wherein VH contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1913, and VL contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2019. Embodiment 6. The α4β7 binding protein according to Embodiment 2, wherein VH contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1914, and VL contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2020. Embodiment 7. The α4β7 binding protein according to Embodiment 2, wherein VH contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1925, and VL contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2031. Embodiment 8. The α4β7 binding protein according to Embodiment 2, wherein VH contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1926, and VL contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2032. Embodiment 9. The α4β7 binding protein according to Embodiment 2, wherein VH contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1927, and VL contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2033. Embodiment 10. The following: a) A heavy chain variable region (VH) comprising (i) CDR1 having an amino acid sequence following any one of SEQ ID NOs: 7-26, 32-58, 60-80, and 84-106; (ii) CDR2 having an amino acid sequence following any one of SEQ ID NOs: 113-132, 138-164, 166-186, and 190-212; and (iii) CDR3 having an amino acid sequence following any one of SEQ ID NOs: 219-238, 244-270, 272-292, and 296-318; b) Light chain variable region (VL) comprising (i) CDR1 having an amino acid sequence following any one of SEQ ID NOs: 325-344, 350-376, 378-398, and 402-424; (ii) CDR2 having an amino acid sequence following any one of SEQ ID NOs: 431-450, 456-482, 484-504, and 508-530; and (iii) CDR3 having an amino acid sequence following any one of SEQ ID NOs: 537-556, 562-588, 590-610, and 614-636. An α4β7 binding protein containing this protein. Embodiment 11. The α4β7 binding protein according to Embodiment 10, wherein VH comprises (i) CDR1 having an amino acid sequence according to SEQ ID NO: 7, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 113, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 219, and VL comprises (i) CDR1 having an amino acid sequence according to SEQ ID NO: 325, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 431, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 537. Embodiment 12. The α4β7 binding protein according to Embodiment 10, wherein VH comprises (i) CDR1 having an amino acid sequence according to SEQ ID NO: 8, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 114, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 220, and VL comprises (i) CDR1 having an amino acid sequence according to SEQ ID NO: 326, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 432, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 538. Embodiment 13. The α4β7 binding protein according to Embodiment 10, wherein VH comprises (i) CDR1 having an amino acid sequence according to SEQ ID NO: 9, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 115, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 221, and VL comprises (i) CDR1 having an amino acid sequence according to SEQ ID NO: 327, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 433, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 539. Embodiment 14. The α4β7 binding protein according to Embodiment 10, wherein VH comprises (i) CDR1 having an amino acid sequence according to SEQ ID NO: 10, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 116, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 222, and VL comprises (i) CDR1 having an amino acid sequence according to SEQ ID NO: 328, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 434, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 540. Embodiment 15. The α4β7 binding protein according to Embodiment 10, wherein VH comprises (i) CDR1 having an amino acid sequence according to SEQ ID NO: 11, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 117, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 223, and VL comprises (i) CDR1 having an amino acid sequence according to SEQ ID NO: 329, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 435, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 541. Embodiment 16. The α4β7 binding protein according to Embodiment 10, wherein VH comprises (i) CDR1 having an amino acid sequence according to SEQ ID NO: 12, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 118, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 224, and VL comprises (i) CDR1 having an amino acid sequence according to SEQ ID NO: 330, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 436, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 542. Embodiment 17. The α4β7 binding protein according to Embodiment 10, wherein VH comprises (i) CDR1 having an amino acid sequence according to SEQ ID NO: 13, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 119, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 225, and VL comprises (i) CDR1 having an amino acid sequence according to SEQ ID NO: 331, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 437, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 543. Embodiment 18. The α4β7 binding protein according to Embodiment 10, wherein VH comprises (i) CDR1 having an amino acid sequence according to SEQ ID NO: 14, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 120, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 226, and VL comprises (i) CDR1 having an amino acid sequence according to SEQ ID NO: 332, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 438, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 544. Embodiment 19. The α4β7 binding protein according to Embodiment 10, wherein VH comprises (i) CDR1 having an amino acid sequence according to SEQ ID NO: 15, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 121, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 227, and VL comprises (i) CDR1 having an amino acid sequence according to SEQ ID NO: 333, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 439, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 545. Embodiment 20. The α4β7 binding protein according to Embodiment 10, wherein VH comprises (i) CDR1 having an amino acid sequence according to SEQ ID NO: 16, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 122, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 228, and VL comprises (i) CDR1 having an amino acid sequence according to SEQ ID NO: 334, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 440, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 546. Embodiment 21. The α4β7 binding protein according to Embodiment 10, wherein VH comprises (i) CDR1 having an amino acid sequence according to SEQ ID NO: 17, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 123, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 229, and VL comprises (i) CDR1 having an amino acid sequence according to SEQ ID NO: 335, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 441, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 547. Embodiment 22. The α4β7 binding protein according to Embodiment 10, wherein VH comprises (i) CDR1 having an amino acid sequence according to SEQ ID NO: 18, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 124, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 230, and VL comprises (i) CDR1 having an amino acid sequence according to SEQ ID NO: 336, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 442, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 548. Embodiment 23. The α4β7 binding protein according to Embodiment 10, wherein VH comprises (i) CDR1 having an amino acid sequence according to SEQ ID NO: 19, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 125, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 231, and VL comprises (i) CDR1 having an amino acid sequence according to SEQ ID NO: 337, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 443, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 549. Embodiment 24. The α4β7 binding protein according to Embodiment 10, wherein VH comprises (i) CDR1 having an amino acid sequence according to SEQ ID NO: 20, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 126, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 232, and VL comprises (i) CDR1 having an amino acid sequence according to SEQ ID NO: 338, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 444, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 550. Embodiment 25. The α4β7 binding protein according to Embodiment 10, wherein VH comprises (i) CDR1 having an amino acid sequence according to SEQ ID NO: 21, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 127, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 233, and VL comprises (i) CDR1 having an amino acid sequence according to SEQ ID NO: 339, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 445, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 551. Embodiment 26. The α4β7 binding protein according to Embodiment 10, wherein VH comprises (i) CDR1 having an amino acid sequence according to SEQ ID NO: 22, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 128, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 234, and VL comprises (i) CDR1 having an amino acid sequence according to SEQ ID NO: 340, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 446, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 552. Embodiment 27. The α4β7 binding protein according to Embodiment 10, wherein VH comprises (i) CDR1 having an amino acid sequence according to SEQ ID NO: 23, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 129, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 235, and VL comprises (i) CDR1 having an amino acid sequence according to SEQ ID NO: 341, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 447, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 553. Embodiment 28. The α4β7 binding protein according to Embodiment 10, wherein VH comprises (i) CDR1 having an amino acid sequence according to SEQ ID NO: 24, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 130, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 236, and VL comprises (i) CDR1 having an amino acid sequence according to SEQ ID NO: 342, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 448, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 554. Embodiment 29. The α4β7 binding protein according to Embodiment 10, wherein VH comprises (i) CDR1 having an amino acid sequence according to SEQ ID NO: 25, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 131, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 237, and VL comprises (i) CDR1 having an amino acid sequence according to SEQ ID NO: 343, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 449, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 555. Embodiment 30. The α4β7 binding protein according to Embodiment 10, wherein VH comprises (i) CDR1 having an amino acid sequence according to SEQ ID NO: 26, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 132, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 238, and VL comprises (i) CDR1 having an amino acid sequence according to SEQ ID NO: 344, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 450, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 556. Embodiment 31. The α4β7 binding protein according to Embodiment 10, wherein VH comprises (i) CDR1 having an amino acid sequence according to SEQ ID NO: 32, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 138, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 244, and VL comprises (i) CDR1 having an amino acid sequence according to SEQ ID NO: 350, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 456, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 562. Embodiment 32. The α4β7 binding protein according to Embodiment 10, wherein VH comprises (i) CDR1 having an amino acid sequence according to SEQ ID NO: 33, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 139, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 245, and VL comprises (i) CDR1 having an amino acid sequence according to SEQ ID NO: 351, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 457, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 563. Embodiment 33. The α4β7 binding protein according to Embodiment 10, wherein VH comprises (i) CDR1 having an amino acid sequence according to SEQ ID NO: 34, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 140, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 246, and VL comprises (i) CDR1 having an amino acid sequence according to SEQ ID NO: 352, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 458, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 564. Embodiment 34. The α4β7 binding protein according to Embodiment 10, wherein VH comprises (i) CDR1 having an amino acid sequence according to SEQ ID NO: 35, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 141, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 247, and VL comprises (i) CDR1 having an amino acid sequence according to SEQ ID NO: 353, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 459, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 565. Embodiment 35. The α4β7 binding protein according to Embodiment 10, wherein VH comprises (i) CDR1 having an amino acid sequence according to SEQ ID NO: 36, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 142, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 248, and VL comprises (i) CDR1 having an amino acid sequence according to SEQ ID NO: 354, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 460, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 566. Embodiment 36. The α4β7 binding protein according to Embodiment 10, wherein VH comprises (i) CDR1 having an amino acid sequence according to SEQ ID NO: 37, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 143, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 249, and VL comprises (i) CDR1 having an amino acid sequence according to SEQ ID NO: 355, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 461, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 567. Embodiment 37. The α4β7 binding protein according to Embodiment 10, wherein VH comprises (i) CDR1 having an amino acid sequence according to SEQ ID NO: 38, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 144, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 250, and VL comprises (i) CDR1 having an amino acid sequence according to SEQ ID NO: 356, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 462, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 568. Embodiment 38. The α4β7 binding protein according to Embodiment 10, wherein VH comprises (i) CDR1 having an amino acid sequence according to SEQ ID NO: 39, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 145, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 251, and VL comprises (i) CDR1 having an amino acid sequence according to SEQ ID NO: 357, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 463, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 569. Embodiment 39. The α4β7 binding protein according to Embodiment 10, wherein VH comprises (i) CDR1 having an amino acid sequence according to SEQ ID NO: 40, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 146, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 252, and VL comprises (i) CDR1 having an amino acid sequence according to SEQ ID NO: 358, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 464, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 570. Embodiment 40. The α4β7 binding protein according to Embodiment 10, wherein VH comprises (i) CDR1 having an amino acid sequence according to SEQ ID NO: 41, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 147, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 253, and VL comprises (i) CDR1 having an amino acid sequence according to SEQ ID NO: 359, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 465, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 571. Embodiment 41. The α4β7 binding protein according to Embodiment 10, wherein VH comprises (i) CDR1 having an amino acid sequence according to SEQ ID NO: 42, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 148, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 254, and VL comprises (i) CDR1 having an amino acid sequence according to SEQ ID NO: 360, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 466, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 572. Embodiment 42. The α4β7 binding protein according to Embodiment 10, wherein VH comprises (i) CDR1 having an amino acid sequence according to SEQ ID NO: 43, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 149, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 255, and VL comprises (i) CDR1 having an amino acid sequence according to SEQ ID NO: 361, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 467, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 573. Embodiment 43. The α4β7 binding protein according to Embodiment 10, wherein VH comprises (i) CDR1 having an amino acid sequence according to SEQ ID NO: 44, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 150, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 256, and VL comprises (i) CDR1 having an amino acid sequence according to SEQ ID NO: 362, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 468, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 574. Embodiment 44. The α4β7 binding protein according to Embodiment 10, wherein VH comprises (i) CDR1 having an amino acid sequence according to SEQ ID NO: 45, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 151, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 257, and VL comprises (i) CDR1 having an amino acid sequence according to SEQ ID NO: 363, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 469, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 575. Embodiment 45. The α4β7 binding protein according to Embodiment 10, wherein VH comprises (i) CDR1 having an amino acid sequence according to SEQ ID NO: 46, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 152, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 258, and VL comprises (i) CDR1 having an amino acid sequence according to SEQ ID NO: 364, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 470, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 576. Embodiment 46. The α4β7 binding protein according to Embodiment 10, wherein VH comprises (i) CDR1 having an amino acid sequence according to SEQ ID NO: 47, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 153, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 259, and VL comprises (i) CDR1 having an amino acid sequence according to SEQ ID NO: 365, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 471, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 577. Embodiment 47. The α4β7 binding protein according to Embodiment 10, wherein VH comprises (i) CDR1 having an amino acid sequence according to SEQ ID NO: 48, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 154, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 260, and VL comprises (i) CDR1 having an amino acid sequence according to SEQ ID NO: 366, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 472, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 578. Embodiment 48. The α4β7 binding protein according to Embodiment 10, wherein VH comprises (i) CDR1 having an amino acid sequence according to SEQ ID NO: 49, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 155, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 261, and VL comprises (i) CDR1 having an amino acid sequence according to SEQ ID NO: 367, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 473, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 579. Embodiment 49. The α4β7 binding protein according to Embodiment 10, wherein VH comprises (i) CDR1 having an amino acid sequence according to SEQ ID NO: 50, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 156, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 262, and VL comprises (i) CDR1 having an amino acid sequence according to SEQ ID NO: 368, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 474, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 580. Embodiment 50. The α4β7 binding protein according to Embodiment 10, wherein the VH comprises (i) CDR1 having an amino acid sequence according to SEQ ID NO: 51, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 157, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 263, and the VL comprises (i) CDR1 having an amino acid sequence according to SEQ ID NO: 369, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 475, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 581. Embodiment 51. The α4β7 binding protein according to Embodiment 10, wherein VH comprises (i) CDR1 having an amino acid sequence according to SEQ ID NO: 52, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 158, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 264, and VL comprises (i) CDR1 having an amino acid sequence according to SEQ ID NO: 370, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 476, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 582. Embodiment 52. The α4β7 binding protein according to Embodiment 10, wherein VH comprises (i) CDR1 having an amino acid sequence according to SEQ ID NO: 53, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 159, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 265, and VL comprises (i) CDR1 having an amino acid sequence according to SEQ ID NO: 371, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 477, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 583. Embodiment 53. The α4β7 binding protein according to Embodiment 10, wherein VH comprises (i) CDR1 having an amino acid sequence according to SEQ ID NO: 54, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 160, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 266, and VL comprises (i) CDR1 having an amino acid sequence according to SEQ ID NO: 372, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 478, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 584. Embodiment 54. The α4β7 binding protein according to Embodiment 10, wherein VH comprises (i) CDR1 having an amino acid sequence according to SEQ ID NO: 55, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 161, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 267, and VL comprises (i) CDR1 having an amino acid sequence according to SEQ ID NO: 373, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 479, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 585. Embodiment 55. The α4β7 binding protein according to Embodiment 10, wherein VH comprises (i) CDR1 having an amino acid sequence according to SEQ ID NO: 56, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 162, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 268, and VL comprises (i) CDR1 having an amino acid sequence according to SEQ ID NO: 374, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 480, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 586. Embodiment 56. The α4β7 binding protein according to Embodiment 10, wherein VH comprises (i) CDR1 having an amino acid sequence according to SEQ ID NO: 57, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 163, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 269, and VL comprises (i) CDR1 having an amino acid sequence according to SEQ ID NO: 375, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 481, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 587. Embodiment 57. The α4β7 binding protein according to Embodiment 10, wherein the VH comprises (i) CDR1 having an amino acid sequence according to SEQ ID NO: 58, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 164, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 270, and the VL comprises (i) CDR1 having an amino acid sequence according to SEQ ID NO: 376, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 482, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 588. Embodiment 58. The α4β7 binding protein according to Embodiment 10, wherein VH comprises (i) CDR1 having an amino acid sequence according to SEQ ID NO: 60, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 166, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 272, and VL comprises (i) CDR1 having an amino acid sequence according to SEQ ID NO: 378, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 484, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 590. Embodiment 59. The α4β7 binding protein according to Embodiment 10, wherein VH comprises (i) CDR1 having an amino acid sequence according to SEQ ID NO: 61, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 167, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 273, and VL comprises (i) CDR1 having an amino acid sequence according to SEQ ID NO: 379, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 485, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 591. Embodiment 60. The α4β7 binding protein according to Embodiment 10, wherein VH comprises (i) CDR1 having an amino acid sequence according to SEQ ID NO: 62, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 168, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 274, and VL comprises (i) CDR1 having an amino acid sequence according to SEQ ID NO: 380, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 486, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 592. Embodiment 61. The α4β7 binding protein according to Embodiment 10, wherein VH comprises (i) CDR1 having an amino acid sequence according to SEQ ID NO: 63, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 169, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 275, and VL comprises (i) CDR1 having an amino acid sequence according to SEQ ID NO: 381, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 487, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 593. Embodiment 62. The α4β7 binding protein according to Embodiment 10, wherein VH comprises (i) CDR1 having an amino acid sequence according to SEQ ID NO: 64, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 170, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 276, and VL comprises (i) CDR1 having an amino acid sequence according to SEQ ID NO: 382, ​​(ii) CDR2 having an amino acid sequence according to SEQ ID NO: 488, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 594. Embodiment 63. The α4β7 binding protein according to Embodiment 10, wherein VH comprises (i) CDR1 having an amino acid sequence according to SEQ ID NO: 65, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 171, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 277, and VL comprises (i) CDR1 having an amino acid sequence according to SEQ ID NO: 383, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 489, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 595. Embodiment 64. The α4β7 binding protein according to Embodiment 10, wherein VH comprises (i) CDR1 having an amino acid sequence according to SEQ ID NO: 66, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 172, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 278, and VL comprises (i) CDR1 having an amino acid sequence according to SEQ ID NO: 384, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 490, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 596. Embodiment 65. The α4β7 binding protein according to Embodiment 10, wherein VH comprises (i) CDR1 having an amino acid sequence according to SEQ ID NO: 67, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 173, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 279, and VL comprises (i) CDR1 having an amino acid sequence according to SEQ ID NO: 385, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 491, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 597. The α4β7 binding protein according to Embodiment 10, wherein the VH comprises (i) CDR1 having an amino acid sequence according to SEQ ID NO: 68, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 174, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 280, and the VL comprises (i) CDR1 having an amino acid sequence according to SEQ ID NO: 386, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 492, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 598. Embodiment 66. The α4β7 binding protein according to Embodiment 10, wherein VH comprises (i) CDR1 having an amino acid sequence according to SEQ ID NO: 69, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 175, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 281, and VL comprises (i) CDR1 having an amino acid sequence according to SEQ ID NO: 387, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 493, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 599. Embodiment 67. The α4β7 binding protein according to Embodiment 10, wherein VH comprises (i) CDR1 having an amino acid sequence according to SEQ ID NO: 70, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 176, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 282, and VL comprises (i) CDR1 having an amino acid sequence according to SEQ ID NO: 388, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 494, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 600. Embodiment 68. The α4β7 binding protein according to Embodiment 10, wherein VH comprises (i) CDR1 having an amino acid sequence according to SEQ ID NO: 71, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 177, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 283, and VL comprises (i) CDR1 having an amino acid sequence according to SEQ ID NO: 389, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 495, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 601. Embodiment 69. The α4β7 binding protein according to Embodiment 10, wherein VH comprises (i) CDR1 having an amino acid sequence according to SEQ ID NO: 72, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 178, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 284, and VL comprises (i) CDR1 having an amino acid sequence according to SEQ ID NO: 390, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 496, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 602. Embodiment 70. The α4β7 binding protein according to Embodiment 10, wherein VH comprises (i) CDR1 having an amino acid sequence according to SEQ ID NO: 73, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 179, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 285, and VL comprises (i) CDR1 having an amino acid sequence according to SEQ ID NO: 391, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 497, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 603. Embodiment 71. The α4β7 binding protein according to Embodiment 10, wherein VH comprises (i) CDR1 having an amino acid sequence according to SEQ ID NO: 74, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 180, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 286, and VL comprises (i) CDR1 having an amino acid sequence according to SEQ ID NO: 392, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 498, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 604. Embodiment 72. The α4β7 binding protein according to Embodiment 10, wherein VH comprises (i) CDR1 having an amino acid sequence according to SEQ ID NO: 75, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 181, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 287, and VL comprises (i) CDR1 having an amino acid sequence according to SEQ ID NO: 393, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 499, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 605. Embodiment 73. The α4β7 binding protein according to Embodiment 10, wherein VH comprises (i) CDR1 having an amino acid sequence according to SEQ ID NO: 76, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 182, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 288, and VL comprises (i) CDR1 having an amino acid sequence according to SEQ ID NO: 394, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 500, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 606. Embodiment 74. The α4β7 binding protein according to Embodiment 10, wherein VH comprises (i) CDR1 having an amino acid sequence according to SEQ ID NO: 77, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 183, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 289, and VL comprises (i) CDR1 having an amino acid sequence according to SEQ ID NO: 395, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 501, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 607. Embodiment 75. The α4β7 binding protein according to Embodiment 10, wherein VH comprises (i) CDR1 having an amino acid sequence according to SEQ ID NO: 78, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 184, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 290, and VL comprises (i) CDR1 having an amino acid sequence according to SEQ ID NO: 396, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 502, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 608. Embodiment 76. The α4β7 binding protein according to Embodiment 10, wherein VH comprises (i) CDR1 having an amino acid sequence according to SEQ ID NO: 79, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 185, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 291, and VL comprises (i) CDR1 having an amino acid sequence according to SEQ ID NO: 397, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 503, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 609. Embodiment 77. The α4β7 binding protein according to Embodiment 10, wherein VH comprises (i) CDR1 having an amino acid sequence according to SEQ ID NO: 80, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 186, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 292, and VL comprises (i) CDR1 having an amino acid sequence according to SEQ ID NO: 398, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 504, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 610. Embodiment 78. The α4β7 binding protein according to Embodiment 10, wherein VH comprises (i) CDR1 having an amino acid sequence according to SEQ ID NO: 84, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 190, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 296, and VL comprises (i) CDR1 having an amino acid sequence according to SEQ ID NO: 402, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 508, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 614. Embodiment 79. The α4β7 binding protein according to Embodiment 10, wherein VH comprises (i) CDR1 having an amino acid sequence according to SEQ ID NO: 85, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 191, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 297, and VL comprises (i) CDR1 having an amino acid sequence according to SEQ ID NO: 403, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 509, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 615. Embodiment 80. The α4β7 binding protein according to Embodiment 10, wherein VH comprises (i) CDR1 having an amino acid sequence according to SEQ ID NO: 86, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 192, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 298, and VL comprises (i) CDR1 having an amino acid sequence according to SEQ ID NO: 404, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 510, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 616. Embodiment 81. The α4β7 binding protein according to Embodiment 10, wherein VH comprises (i) CDR1 having an amino acid sequence according to SEQ ID NO: 87, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 193, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 299, and VL comprises (i) CDR1 having an amino acid sequence according to SEQ ID NO: 405, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 511, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 617. Embodiment 82. The α4β7 binding protein according to Embodiment 10, wherein VH comprises (i) CDR1 having an amino acid sequence according to SEQ ID NO: 88, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 194, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 300, and VL comprises (i) CDR1 having an amino acid sequence according to SEQ ID NO: 406, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 512, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 618. Embodiment 83. The α4β7 binding protein according to Embodiment 10, wherein VH comprises (i) CDR1 having an amino acid sequence according to SEQ ID NO: 89, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 195, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 301, and VL comprises (i) CDR1 having an amino acid sequence according to SEQ ID NO: 407, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 513, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 619. Embodiment 84. The α4β7 binding protein according to Embodiment 10, wherein VH comprises (i) CDR1 having an amino acid sequence according to SEQ ID NO: 90, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 196, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 302, and VL comprises (i) CDR1 having an amino acid sequence according to SEQ ID NO: 408, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 514, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 620. Embodiment 85. The α4β7 binding protein according to Embodiment 10, wherein VH comprises (i) CDR1 having an amino acid sequence according to SEQ ID NO: 91, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 197, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 303, and VL comprises (i) CDR1 having an amino acid sequence according to SEQ ID NO: 409, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 515, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 621. Embodiment 86. The α4β7 binding protein according to Embodiment 10, wherein VH comprises (i) CDR1 having an amino acid sequence according to SEQ ID NO: 92, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 198, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 304, and VL comprises (i) CDR1 having an amino acid sequence according to SEQ ID NO: 410, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 516, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 622. Embodiment 87. The α4β7 binding protein according to Embodiment 10, wherein VH comprises (i) CDR1 having an amino acid sequence according to SEQ ID NO: 93, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 199, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 305, and VL comprises (i) CDR1 having an amino acid sequence according to SEQ ID NO: 411, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 517, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 623. Embodiment 88. The α4β7 binding protein according to Embodiment 10, wherein VH comprises (i) CDR1 having an amino acid sequence according to SEQ ID NO: 94, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 200, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 306, and VL comprises (i) CDR1 having an amino acid sequence according to SEQ ID NO: 412, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 518, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 624. Embodiment 89. The α4β7 binding protein according to Embodiment 10, wherein VH comprises (i) CDR1 having an amino acid sequence according to SEQ ID NO: 95, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 201, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 307, and VL comprises (i) CDR1 having an amino acid sequence according to SEQ ID NO: 413, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 519, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 625. Embodiment 90. The α4β7 binding protein according to Embodiment 10, wherein VH comprises (i) CDR1 having an amino acid sequence according to SEQ ID NO: 96, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 202, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 308, and VL comprises (i) CDR1 having an amino acid sequence according to SEQ ID NO: 414, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 520, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 626. Embodiment 91. The α4β7 binding protein according to Embodiment 10, wherein VH comprises (i) CDR1 having an amino acid sequence according to SEQ ID NO: 97, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 203, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 309, and VL comprises (i) CDR1 having an amino acid sequence according to SEQ ID NO: 415, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 521, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 627. Embodiment 92. The α4β7 binding protein according to Embodiment 10, wherein VH comprises (i) CDR1 having an amino acid sequence according to SEQ ID NO: 98, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 204, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 310, and VL comprises (i) CDR1 having an amino acid sequence according to SEQ ID NO: 416, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 522, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 628. Embodiment 93. The α4β7 binding protein according to Embodiment 10, wherein VH comprises (i) CDR1 having an amino acid sequence according to SEQ ID NO: 99, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 205, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 311, and VL comprises (i) CDR1 having an amino acid sequence according to SEQ ID NO: 417, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 523, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 629. Embodiment 94. The α4β7 binding protein according to Embodiment 10, wherein VH comprises (i) CDR1 having an amino acid sequence according to SEQ ID NO: 100, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 206, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 312, and VL comprises (i) CDR1 having an amino acid sequence according to SEQ ID NO: 418, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 524, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 630. Embodiment 95. The α4β7 binding protein according to Embodiment 10, wherein VH comprises (i) CDR1 having an amino acid sequence according to SEQ ID NO: 101, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 207, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 313, and VL comprises (i) CDR1 having an amino acid sequence according to SEQ ID NO: 419, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 525, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 631. Embodiment 96. The α4β7 binding protein according to Embodiment 10, wherein the VH comprises (i) CDR1 having an amino acid sequence according to SEQ ID NO: 102, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 208, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 314, and the VL comprises (i) CDR1 having an amino acid sequence according to SEQ ID NO: 420, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 526, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 632. Embodiment 97. The α4β7 binding protein according to Embodiment 10, wherein VH comprises (i) CDR1 having an amino acid sequence according to SEQ ID NO: 103, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 209, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 315, and VL comprises (i) CDR1 having an amino acid sequence according to SEQ ID NO: 421, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 527, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 633. Embodiment 98. The α4β7 binding protein according to Embodiment 10, wherein VH comprises (i) CDR1 having an amino acid sequence according to SEQ ID NO: 104, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 210, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 316, and VL comprises (i) CDR1 having an amino acid sequence according to SEQ ID NO: 422, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 528, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 634. Embodiment 99. The α4β7 binding protein according to Embodiment 10, wherein VH comprises (i) CDR1 having an amino acid sequence according to SEQ ID NO: 105, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 211, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 317, and VL comprises (i) CDR1 having an amino acid sequence according to SEQ ID NO: 423, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 529, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 635. Embodiment 100. The α4β7 binding protein according to Embodiment 10, wherein the VH comprises (i) CDR1 having an amino acid sequence according to SEQ ID NO: 106, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 212, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 318, and the VL comprises (i) CDR1 having an amino acid sequence according to SEQ ID NO: 424, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 530, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 636. Embodiment 101. An α4β7 binding protein according to any one of Embodiments 10 to 100, wherein VH contains a sequence having at least 80% sequence identity with respect to any one of the amino acid sequences among SEQ ID NOs. 1915-1934, 1940-1966, 1968-1988, and 1992-2014, and VL contains a sequence having at least 80% sequence identity with respect to any one of the amino acid sequences among SEQ ID NOs. 2021-2040, 2046-2072, 2074-2094, and 2098-2120. Embodiment 102. The α4β7 binding protein according to Embodiment 101, wherein VH contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 127, and VL contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 134. Embodiment 103. The α4β7 binding protein according to Embodiment 101, wherein VH contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1915, and VL contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2021. Embodiment 104. The α4β7 binding protein according to Embodiment 101, wherein VH contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1916, and VL contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2022. Embodiment 105. The α4β7 binding protein according to Embodiment 101, wherein VH contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1917, and VL contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2023. Embodiment 106. The α4β7 binding protein according to Embodiment 101, wherein VH contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1918, and VL contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2024. Embodiment 107. The α4β7 binding protein according to Embodiment 101, wherein VH contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1919, and VL contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2025. Embodiment 108. The α4β7 binding protein according to Embodiment 101, wherein VH contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1920, and VL contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2026. Embodiment 109. The α4β7 binding protein according to Embodiment 101, wherein VH contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1921, and VL contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2027. Embodiment 110. The α4β7 binding protein according to Embodiment 101, wherein VH contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1922, and VL contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2028. Embodiment 111. The α4β7 binding protein according to Embodiment 101, wherein VH contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1923, and VL contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2029. Embodiment 112. The α4β7 binding protein according to Embodiment 101, wherein VH contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1924, and VL contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2030. Embodiment 113. The α4β7 binding protein according to Embodiment 101, wherein VH contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1925, and VL contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2031. Embodiment 114. The α4β7 binding protein according to Embodiment 101, wherein VH contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1926, and VL contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2032. Embodiment 115. The α4β7 binding protein according to Embodiment 101, wherein VH contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1927, and VL contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2033. Embodiment 116. The α4β7 binding protein according to Embodiment 101, wherein VH contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1928, and VL contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2034. Embodiment 117. The α4β7 binding protein according to Embodiment 101, wherein VH contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1929, and VL contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2035. Embodiment 118. The α4β7 binding protein according to Embodiment 101, wherein VH contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1930, and VL contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2036. Embodiment 119. The α4β7 binding protein according to Embodiment 101, wherein VH contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1931, and VL contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2037. Embodiment 120. The α4β7 binding protein according to Embodiment 101, wherein VH contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1932, and VL contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2038. Embodiment 121. The α4β7 binding protein according to Embodiment 101, wherein VH contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1933, and VL contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2039. Embodiment 122. The α4β7 binding protein according to Embodiment 101, wherein VH contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1934, and VL contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2040. Embodiment 123. The α4β7 binding protein according to Embodiment 101, wherein VH contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1940, and VL contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2046. Embodiment 124. The α4β7 binding protein according to Embodiment 101, wherein VH contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1941, and VL contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2047. Embodiment 125. The α4β7 binding protein according to Embodiment 101, wherein VH contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1942, and VL contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2048. Embodiment 126. The α4β7 binding protein according to Embodiment 101, wherein VH contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1943, and VL contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2049. Embodiment 127. The α4β7 binding protein according to Embodiment 101, wherein VH contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1944, and VL contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2050. Embodiment 128. The α4β7 binding protein according to Embodiment 101, wherein VH contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1945, and VL contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2051. Embodiment 129. The α4β7 binding protein according to Embodiment 101, wherein VH contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1946, and VL contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2052. Embodiment 130. The α4β7 binding protein according to Embodiment 101, wherein VH contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1947, and VL contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2053. Embodiment 131. The α4β7 binding protein according to Embodiment 101, wherein VH contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1948, and VL contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2054. Embodiment 132. The α4β7 binding protein according to Embodiment 101, wherein VH contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1949, and VL contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2055. Embodiment 133. The α4β7 binding protein according to Embodiment 101, wherein VH contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1950, and VL contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2056. Embodiment 134. The α4β7 binding protein according to Embodiment 101, wherein VH contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1951, and VL contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2057. Embodiment 135. The α4β7 binding protein according to Embodiment 101, wherein VH contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1952, and VL contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2058. Embodiment 136. The α4β7 binding protein according to Embodiment 101, wherein VH contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1953, and VL contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2059. Embodiment 137. The α4β7 binding protein according to Embodiment 101, wherein VH contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1954, and VL contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2060. Embodiment 138. The α4β7 binding protein according to Embodiment 101, wherein VH contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1955, and VL contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2061. Embodiment 139. The α4β7 binding protein according to Embodiment 101, wherein VH contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1956, and VL contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2062. Embodiment 140. The α4β7 binding protein according to Embodiment 101, wherein VH contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1957, and VL contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2063. Embodiment 141. The α4β7 binding protein according to Embodiment 101, wherein VH contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1958, and VL contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2064. Embodiment 142. The α4β7 binding protein according to Embodiment 101, wherein VH contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1959, and VL contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2065. Embodiment 143. The α4β7 binding protein according to Embodiment 101, wherein VH contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1960, and VL contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2066. Embodiment 144. The α4β7 binding protein according to Embodiment 101, wherein VH contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1961, and VL contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2067. Embodiment 145. The α4β7 binding protein according to Embodiment 101, wherein VH contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1962, and VL contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2068. Embodiment 146. The α4β7 binding protein according to Embodiment 101, wherein VH contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1963, and VL contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2069. Embodiment 147. The α4β7 binding protein according to Embodiment 101, wherein VH contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1964, and VL contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2070. Embodiment 148. The α4β7 binding protein according to Embodiment 101, wherein VH contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1965, and VL contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2071. Embodiment 149. The α4β7 binding protein according to Embodiment 101, wherein VH contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1966, and VL contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2072. Embodiment 150. The α4β7 binding protein according to Embodiment 101, wherein VH contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1968, and VL contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2074. Embodiment 151. The α4β7 binding protein according to Embodiment 101, wherein VH contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1969, and VL contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2075. Embodiment 152. The α4β7 binding protein according to Embodiment 101, wherein VH contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1970, and VL contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2076. Embodiment 153. The α4β7 binding protein according to Embodiment 101, wherein VH contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1971, and VL contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2077. Embodiment 154. The α4β7 binding protein according to Embodiment 101, wherein VH contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1972, and VL contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2078. Embodiment 155. The α4β7 binding protein according to Embodiment 101, wherein VH contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1973, and VL contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2079. Embodiment 156. The α4β7-binding protein according to Embodiment 101, wherein VH contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1974, and VL contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2080. Embodiment 157. The α4β7-binding protein according to Embodiment 101, wherein VH contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1975, and VL contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2081. Embodiment 158. The α4β7 binding protein according to Embodiment 101, wherein VH contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1976, and VL contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2082. Embodiment 159. The α4β7 binding protein according to Embodiment 101, wherein VH contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1977, and VL contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2083. Embodiment 160. The α4β7 binding protein according to Embodiment 101, wherein VH contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1978, and VL contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2084. Embodiment 161. The α4β7 binding protein according to Embodiment 101, wherein VH contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1979, and VL contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2085. Embodiment 162. The α4β7 binding protein according to Embodiment 101, wherein VH contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1980, and VL contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2086. Embodiment 163. The α4β7 binding protein according to Embodiment 101, wherein VH contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1981, and VL contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2087. Embodiment 164. The α4β7 binding protein according to Embodiment 101, wherein VH contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1982, and VL contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2088. Embodiment 165. The α4β7 binding protein according to Embodiment 101, wherein VH contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1983, and VL contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2089. Embodiment 166. The α4β7 binding protein according to Embodiment 101, wherein VH contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1984, and VL contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2090. Embodiment 167. The α4β7 binding protein according to Embodiment 101, wherein VH contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1985, and VL contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2091. Embodiment 168. The α4β7 binding protein according to Embodiment 101, wherein VH contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1986, and VL contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2092. Embodiment 169. The α4β7 binding protein according to Embodiment 101, wherein VH contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1987, and VL contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2093. Embodiment 170. The α4β7 binding protein according to Embodiment 101, wherein VH contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1992, and VL contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2098. Embodiment 171. The α4β7 binding protein according to Embodiment 101, wherein VH contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1993, and VL contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2099. Embodiment 172. The α4β7 binding protein according to Embodiment 101, wherein VH contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1994, and VL contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2100. Embodiment 173. The α4β7 binding protein according to Embodiment 101, wherein VH contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1995, and VL contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2101. Embodiment 174. The α4β7 binding protein according to Embodiment 101, wherein VH contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1996, and VL contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2102. Embodiment 175. The α4β7 binding protein according to Embodiment 101, wherein VH contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1997, and VL contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2103. Embodiment 176. The α4β7 binding protein according to Embodiment 101, wherein VH contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1998, and VL contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2104. Embodiment 177. The α4β7 binding protein according to Embodiment 101, wherein VH contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1999, and VL contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2105. Embodiment 178. The α4β7 binding protein according to Embodiment 101, wherein VH contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2000, and VL contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2106. Embodiment 179. The α4β7 binding protein according to Embodiment 101, wherein VH contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2001, and VL contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2107. Embodiment 180. The α4β7 binding protein according to Embodiment 101, wherein VH contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2002, and VL contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2108. Embodiment 181. The α4β7 binding protein according to Embodiment 101, wherein VH contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2003, and VL contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2109. Embodiment 182. The α4β7 binding protein according to Embodiment 101, wherein VH contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2004, and VL contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2110. Embodiment 183. The α4β7 binding protein according to Embodiment 101, wherein VH contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2005, and VL contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2111. Embodiment 184. The α4β7 binding protein according to Embodiment 101, wherein VH contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2006, and VL contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2112. Embodiment 185. The α4β7 binding protein according to Embodiment 101, wherein VH contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2007, and VL contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2113. Embodiment 186. The α4β7 binding protein according to Embodiment 101, wherein VH contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2008, and VL contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2114. Embodiment 187. The α4β7 binding protein according to Embodiment 101, wherein VH contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2009, and VL contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2115. Embodiment 188. The α4β7 binding protein according to Embodiment 101, wherein VH contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2010, and VL contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2116. Embodiment 189. The α4β7 binding protein according to Embodiment 101, wherein VH contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2011, and VL contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2117. Embodiment 190. The α4β7 binding protein according to Embodiment 101, wherein VH contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2012, and VL contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2118. Embodiment 191. The α4β7 binding protein according to Embodiment 101, wherein VH contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2013, and VL contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2119. Embodiment 192. The α4β7 binding protein according to Embodiment 101, wherein VH contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2014, and VL contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2120. Embodiment 193. Hereafter: a) A heavy chain variable region (VH) containing an amino acid sequence that follows one of sequence numbers 1909, 1910, 1935-1939, and 1967, and b) A light chain variable region (VL) containing an amino acid sequence that follows one of the following sequence numbers: 2015, 2016, 2041-2045, or 2073. An α4β7 binding protein containing this protein. Embodiment 194. The α4β7 binding protein according to Embodiment 193, wherein VH comprises an amino acid sequence according to SEQ ID NO: 1909, and VL comprises an amino acid sequence according to SEQ ID NO: 2015. Embodiment 195. The α4β7 binding protein according to Embodiment 193, wherein VH comprises an amino acid sequence according to SEQ ID NO: 1910, and VL comprises an amino acid sequence according to SEQ ID NO: 2016. Embodiment 196. The α4β7 binding protein according to Embodiment 193, wherein VH comprises an amino acid sequence according to SEQ ID NO: 1935, and VL comprises an amino acid sequence according to SEQ ID NO: 2041. Embodiment 197. The α4β7 binding protein according to Embodiment 193, wherein VH comprises an amino acid sequence according to SEQ ID NO: 1936, and VL comprises an amino acid sequence according to SEQ ID NO: 2042. Embodiment 198. The α4β7 binding protein according to Embodiment 193, wherein VH comprises an amino acid sequence according to SEQ ID NO: 1937, and VL comprises an amino acid sequence according to SEQ ID NO: 2043. Embodiment 199. The α4β7 binding protein according to Embodiment 193, wherein VH comprises an amino acid sequence according to SEQ ID NO: 1938, and VL comprises an amino acid sequence according to SEQ ID NO: 2044. Embodiment 200. The α4β7 binding protein according to Embodiment 193, wherein VH comprises an amino acid sequence according to SEQ ID NO: 1939 and VL comprises an amino acid sequence according to SEQ ID NO: 2045. Embodiment 201. The α4β7 binding protein according to Embodiment 193, wherein VH comprises an amino acid sequence according to SEQ ID NO: 1967, and VL comprises an amino acid sequence according to SEQ ID NO: 2073. Embodiment 202. Hereinafter: c) A heavy chain variable region (VH) comprising (i) CDR1 having an amino acid sequence according to any one of SEQ ID NOs: 1 to 106, (ii) CDR2 having an amino acid sequence according to any one of SEQ ID NOs: 107 to 212, and (iii) CDR3 having an amino acid sequence according to any one of SEQ ID NOs: 213 to 318. d) A light chain variable region (VL) comprising (i) CDR1 having an amino acid sequence according to any one of SEQ ID NOs. 319 to 424, (ii) CDR2 having an amino acid sequence according to any one of SEQ ID NOs. 425 to 530, and (iii) CDR3 having an amino acid sequence according to any one of SEQ ID NOs. 531 to 636, e) Modified Fc including amino acid modifications M252Y, S254T, and T256E(YTE) and / or L234A / G237A(LAGA) An α4β7 binding protein containing this protein. Embodiment 203. The following: a) A heavy chain variable region (VH) comprising (i) CDR1 having an amino acid sequence according to any one of SEQ ID NOs: 1 to 106, (ii) CDR2 having an amino acid sequence according to any one of SEQ ID NOs: 107 to 212, and (iii) CDR3 having an amino acid sequence according to any one of SEQ ID NOs: 213 to 318. b) A light chain variable region (VL) comprising (i) CDR1 having an amino acid sequence according to any one of SEQ ID NOs. 319 to 424, (ii) CDR2 having an amino acid sequence according to any one of SEQ ID NOs. 425 to 530, and (iii) CDR3 having an amino acid sequence according to any one of SEQ ID NOs. 531 to 636, c) A modified Fc that extends the half-life of the α4β7-binding protein compared to an α4β7-binding protein that does not contain the modified Fc. An α4β7 binding protein containing this protein. Embodiment 204. An α4β7-binding protein that specifically binds to the α4β7 epitope and comprises an Fc domain including amino acid modifications M252Y, S254T, and T256E (YTE) and / or L234A / G237A (LAGA). Embodiment 205. The α4β7 binding protein according to any one of Embodiments 202 to 204, wherein the Fc is an IgG1 immunoglobulin Fc domain, an IgG2 immunoglobulin Fc domain, or an IgG4 immunoglobulin Fc domain. Embodiment 206. The α4β7 binding protein according to Embodiment 205, wherein the Fc is an IgG1 immunoglobulin domain. Embodiment 207. The α4β7 binding protein according to Embodiment 205, wherein the Fc is an IgG2 immunoglobulin domain. Embodiment 208. The α4β7 binding protein according to Embodiment 205, wherein the Fc is an IgG4 immunoglobulin domain. Embodiment 209. A method for treating inflammatory bowel disease in a patient requiring treatment for inflammatory bowel disease, comprising the step of subcutaneously or intravenously administering an effective amount of α4β7 binding protein described in any one of Embodiments 1 to 208 to the patient. Embodiment 210. The method according to Embodiment 209, wherein the inflammatory bowel disease is Crohn's disease or ulcerative colitis. Embodiment 211. The method according to Embodiment 210, wherein the inflammatory bowel disease is ulcerative colitis. Embodiment 212. The method according to Embodiment 210, wherein the inflammatory bowel disease is Crohn's disease. Embodiment 213. The method according to any one of Embodiments 209 to 212, wherein the administration of the α4β7 binding protein is subcutaneous. Embodiment 214. The method according to any one of Embodiments 209 to 212, wherein the administration of the α4β7 binding protein is intravenous. Embodiment 215. A method for treating an inflammatory disease in a patient requiring treatment for an inflammatory disease, comprising the step of subcutaneously or intravenously administering an effective amount of the α4β7 binding protein described in any one of Embodiments 1 to 208 to the patient. Embodiment 216. The method according to Embodiment 215, wherein the inflammatory disease is psoriasis. Embodiment 217. The method according to Embodiment 215, wherein the inflammatory disease is psoriatic arthritis. Embodiment 218. The method according to Embodiment 215, wherein the inflammatory disease is hidradenitis suppurativa. Embodiment 219. The method according to any one of Embodiments 215 to 218, wherein the administration of the α4β7 binding protein is subcutaneous. Embodiment 220. The method according to any one of Embodiments 215 to 218, wherein the administration of the α4β7 binding protein is intravenous. Embodiment 221. An isolated nucleic acid encoding an α4β7 binding protein as described in any one of Embodiments 1 to 208. Embodiment 222. Recombinant host cells containing the isolated nucleic acid described in Embodiment 221. [Examples]

[0302] Examples The disclosure described herein in general terms will be more readily understood by referring to the following examples. These examples are included solely for illustrative purposes of certain aspects and embodiments of the disclosure and are not intended to limit the disclosure.

[0303] Example 1. In Silico affinity maturation and liability removal of an anti-α4β7 integrin comparator antibody. Residual scanning analysis was performed on a humanized anti-α4β7 integrin control antibody derived from the parent antibody ACT-1. The three-dimensional structure of ACT-1, complexed with the target antigen, human integrin α4β7 integrin (PDB code 3V4P), was loaded into MOE software.

[0304] Prior to analysis, the antibody structure was optimized using MOE's automated structure preparation workflow. Structural problems such as missing atoms or geometric outliers were corrected, and any other non-essential crystallographic molecules were removed to prepare the antibody model for residue scanning analysis. Hydrogen atoms were added to the model using the Protonate 3D module in MOE while maintaining physiological pH conditions. Constrained minimization was then performed to complete the preparation. Six complementarity-determining regions (CDRs) were identified using the MOE antibody module. Each CDR region was thoroughly tested, and the residues involved were noted for further analysis.

[0305] A systematic scan of all residues in the CDR region was performed using MOE's residue scanning tool. Each residue was mutated one by one with all 19 other native amino acids except cysteine, and the effects on binding affinity, stability, and other protein properties were predicted using MOE's scoring function. Based on the results, the inventors identified key residues in the CDR region that could be mutated without negatively affecting the binding affinity, stability, or development potential of the comparison antibody. The combinations of mutations identified within each CDR were then evaluated in a similar manner. The results are summarized in Table 4. Table 4. Affinity and stability of α4β7 antibodies [Table 4-1] [Table 4-2] [Table 4-3] Δ affinity is a measure of the predicted change in affinity from the control antibody. The absolute value of the number corresponds to the magnitude of the predicted improvement. An improvement in affinity is indicated by a negative value. The value is a unitless prediction. ΔStability is a measure of the predicted change in stability from the control antibody. The absolute value of the number corresponds to the magnitude of the predicted improvement. A negative value indicates an improvement in stability. The value is a unitless prediction.

[0306] Example 2. Re-humanization of an anti-α4β7 integrin comparator antibody. We humanized the parental mouse anti-human α4β7 ACT-1 mouse antibody (the parental monoclonal antibody of the comparator antibody) using a complementarity-determining region (CDR) grafting approach. The parental mouse heavy and light chain sequences were modeled on a human antibody framework. A pair of human heavy and light chains was selected for humanization. The objective was to design these heavy and light chain pairs to improve the biophysical properties of the parental antibody while retaining the α4β7 integrin binding. These humanized molecules were designed to improve the development feasibility profile during scale-up in bioprocesses.

[0307] Example 3. Determination of antibody affinity for α4β7 integrin Using an SPR system equipped with a CM5 tip functionalized with anti-human Fc antibody, the binding kinetic rate and affinity constant were determined at 25°C in HBS-P+ running buffer supplemented with 1 mM Mn2+, 1 mM Ca2+, and 1 mM Mg2+. After a stabilization period in the running buffer, pre-diluted antibodies at 1–1.5 μg / mL were captured on the tip at a flow rate of 10 μL / min for 30 seconds. Subsequently, recombinant human α4β7 integrin was prepared at concentrations of 1.563 nM, 3.125 nM, 6.25 nM, 12.5 nM, 25 nM, 50 nM, and 100 nM, injected at a flow rate of 30 μL / min for 180 seconds, and then the dissociation phase was performed in running buffer only at a flow rate of 30 μL / min for 1200 seconds. The sample was injected onto newly captured mAbs using a multi-cycle method by regenerating the capture surface by injecting 10 mM glycine (pH 1.5). The data was processed and analyzed using SPR analysis software, and the sensorgram was fitted to a 1:1 binding model to determine the apparent association (ka) and dissociation rate constant (kd). From their ratio, the apparent equilibrium dissociation constant or affinity constant (KD = kd / ka) was obtained. The results are summarized in Table 5. Table 5 [Table 5]

[0308] Example 4. Binding to α4β7 integrin or α4β1 integrin on cells. Antibody binding to α4β7 integrin or α4β1 integrin expressed on cells was determined using FACS and two cell lines. The first cell line was RPMI-8866, known to express only α4β7 integrin. The second cell line was Ramos, known to express only α4β1. Briefly, cells were cultured and harvested according to standard distributor instructions. Cells were stained with purified antibodies at concentrations of 0 nM, 0.0064 nM, 0.032 nM, 0.16 nM, 0.8 nM, 4 nM, 20 nM, and 100 nM and incubated at 4°C for 1 hour. Cells were then stained with Alexa Fluor 488-conjugated goat anti-human IgG secondary antibody at a 1:1000 dilution. Cells were incubated at 4°C for 1 hour and protected from light. Cells were then washed, and the MFI of cells in each well was recorded using a flow cytometer by FACS. The subsequent data were analyzed using GraphPad Prism. The EC50 value was determined as the antibody concentration required to achieve 50% of the maximum plateau MFI. The anti-α4β7 integrin control antibody, as well as antibody 1 and antibody 2, showed specific binding to RPMI-8866 but not to Ramos cells. On the other hand, the tested anti-α4 antibody bound to both cell lines. The results are summarized in Table 6 and shown in Figures 1 and 2. Table 6 [Table 6] NB - No binding was observed within the tested concentration range.

[0309] Example 5. Inhibition of cell adhesion via MAdCAM-1 and α4β7 integrin or VCAM-1 and α4β1 integrin Integrins mediate cell adhesion by binding to different cell adhesion molecules. Specifically, α4β7 integrin mediates adhesion via the binding of MAdCAM-1, while α4β7 integrin mediates adhesion via the binding of VCAM-1. To determine the ability of antibodies to block cell adhesion mediated by either α4β7 integrin:MAdCAM-1 interaction or α4β1 integrin:VCAM-1, cell adhesion assays were performed using HuT-78 cells, which have been shown to express both α4β7 and α4β1. Briefly, plates were pre-prepared by coating the wells with either MAdCAM-1 diluted to 0.4 μg / mL in PBS or VCAM-1 diluted to 0.5 μg / mL in PBS. Plates were incubated overnight at 4°C. The following day, cells were harvested according to standard vendor instructions. 1 × 10⁶ cells per 1 mL 6 Cells were stained with calcein AM using a ratio of 1 μL of 1 mM calcein AM per cell. Cells were incubated at 37°C for 30 minutes. Subsequently, the cells were washed and resuspended at a density of 800,000 cells / mL in assay medium consisting of DMEM, 0.1% BSA, 10 mM HEPES, and 0.5 mM MnCl2. Purified antibodies were mixed with cells in a 1:1 volume ratio, gently centrifuged at 10 × g for 1 minute, and incubated at 37°C for 30 minutes. Antibodies were used at final concentrations of 0 nM, 0.0125 nM, 0.025 nM, 0.05 nM, 0.1 nM, 0.2 nM, 0.4 nM, and 2 nM. Individual well fluorescence values ​​were read using a plate reader at 485 nm excitation and 520 nm emission. The wells were then gently washed twice with wash buffer, and the plates were analyzed again in the same manner. The subsequent data were analyzed using GraphPad Prism. The IC50 value was determined as the antibody concentration required to inhibit 50% of the observed maximum cell adhesion. The control antibody and variant antibody showed specific inhibition of MAdCAM-1-mediated cell adhesion, but not of VCAM-1-mediated adhesion. On the other hand, the tested anti-α4 antibody was able to inhibit VCAM-1-mediated cell adhesion. The results are summarized in Table 7 and shown in Figures 3 and 4. Table 7 [Table 7] NT - Not tested. No inhibition was observed within the NI-tested concentration range.

[0310] Equal parts This disclosure can be embodied in other specific forms without departing from its intent or essential features. Therefore, the embodiments described above should be considered in all respects as illustrative rather than limiting the disclosure set forth herein. Accordingly, the scope of this disclosure is indicated by the appended claims rather than by the foregoing description, and all modifications within the same meaning and scope as the claims are intended to be included in the present invention.

Claims

1. below: (a) a heavy chain variable region (VH) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 7, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 113, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 219, and (b) A light chain variable region (VL) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 325, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 431, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO:

537. (a) a heavy chain variable region (VH) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 8, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 114, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 220, and (b) A light chain variable region (VL) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 326, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 432, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO:

538. (a) a heavy chain variable region (VH) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 9, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 115, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 221, and (b) A light chain variable region (VL) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 327, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 433, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO:

539. (a) A heavy chain variable region (VH) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 10, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 116, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 222, and (b) A light chain variable region (VL) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 328, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 434, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO:

540. (a) a heavy chain variable region (VH) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 11, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 117, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 223, and (b) A light chain variable region (VL) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 329, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 435, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO:

541. (a) a heavy chain variable region (VH) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 12, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 118, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 224, and (b) A light chain variable region (VL) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 330, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 436, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO:

542. (a) a heavy chain variable region (VH) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 13, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 119, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 225, and (b) A light chain variable region (VL) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 331, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 437, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO:

543. (a) a heavy chain variable region (VH) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 14, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 120, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 226, and (b) A light chain variable region (VL) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 332, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 438, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO:

544. (a) a heavy chain variable region (VH) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 15, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 121, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 227, and (b) A light chain variable region (VL) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 333, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 439, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO:

545. (a) a heavy chain variable region (VH) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 16, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 122, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 228, and (b) A light chain variable region (VL) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 334, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 440, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO:

546. (a) a heavy chain variable region (VH) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 17, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 123, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 229, and (b) A light chain variable region (VL) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 335, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 441, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO:

547. (a) a heavy chain variable region (VH) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 18, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 124, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 230, and (b) A light chain variable region (VL) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 336, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 442, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO:

548. (a) a heavy chain variable region (VH) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 19, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 125, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 231, and (b) A light chain variable region (VL) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 337, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 443, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO:

549. (a) a heavy chain variable region (VH) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 20, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 126, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 232, and (b) A light chain variable region (VL) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 338, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 444, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO:

550. (a) a heavy chain variable region (VH) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 21, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 127, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 233, and (b) A light chain variable region (VL) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 339, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 445, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO:

551. (a) a heavy chain variable region (VH) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 22, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 128, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 234, and (b) A light chain variable region (VL) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 340, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 446, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO:

552. (a) a heavy chain variable region (VH) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 23, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 129, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 235, and (b) A light chain variable region (VL) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 341, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 447, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO:

553. (a) a heavy chain variable region (VH) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 24, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 130, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 236, and (b) A light chain variable region (VL) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 342, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 448, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO:

554. (a) a heavy chain variable region (VH) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 25, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 131, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 237, and (b) A light chain variable region (VL) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 343, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 449, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO:

555. (a) a heavy chain variable region (VH) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 26, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 132, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 238, and (b) A light chain variable region (VL) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 344, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 450, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO:

556. (a) a heavy chain variable region (VH) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 32, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 138, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 244, and (b) A light chain variable region (VL) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 350, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 456, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO:

562. (a) A heavy chain variable region (VH) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 33, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 139, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 245, and (b) A light chain variable region (VL) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 351, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 457, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO:

563. (a) a heavy chain variable region (VH) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 34, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 140, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 246, and (b) A light chain variable region (VL) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 352, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 458, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO:

564. (a) a heavy chain variable region (VH) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 35, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 141, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 247, and (b) A light chain variable region (VL) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 353, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 459, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO:

565. (a) A heavy chain variable region (VH) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 36, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 142, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 248, and (b) A light chain variable region (VL) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 354, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 460, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO:

566. (a) a heavy chain variable region (VH) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 37, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 143, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 249, and (b) A light chain variable region (VL) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 355, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 461, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO:

567. (a) a heavy chain variable region (VH) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 38, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 144, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 250, and (b) A light chain variable region (VL) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 356, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 462, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO:

568. (a) a heavy chain variable region (VH) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 39, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 145, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 251, and (b) A light chain variable region (VL) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 357, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 463, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO:

569. (a) A heavy chain variable region (VH) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 40, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 146, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 252, and (b) A light chain variable region (VL) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 358, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 464, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO:

570. (a) a heavy chain variable region (VH) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 41, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 147, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 253, and (b) A light chain variable region (VL) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 359, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 465, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO:

571. (a) a heavy chain variable region (VH) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 42, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 148, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 254, and (b) A light chain variable region (VL) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 360, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 466, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO:

572. (a) a heavy chain variable region (VH) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 43, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 149, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 255, and (b) A light chain variable region (VL) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 361, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 467, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO:

573. (a) a heavy chain variable region (VH) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 44, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 150, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 256, and (b) A light chain variable region (VL) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 362, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 468, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO:

574. (a) A heavy chain variable region (VH) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 45, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 151, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 257, and (b) A light chain variable region (VL) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 363, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 469, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO:

575. (a) a heavy chain variable region (VH) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 46, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 152, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 258, and (b) A light chain variable region (VL) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 364, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 470, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO:

576. (a) a heavy chain variable region (VH) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 47, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 153, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 259, and (b) A light chain variable region (VL) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 365, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 471, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO:

577. (a) a heavy chain variable region (VH) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 48, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 154, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 260, and (b) A light chain variable region (VL) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 366, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 472, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO:

578. (a) a heavy chain variable region (VH) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 49, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 155, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 261, and (b) A light chain variable region (VL) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 367, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 473, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO:

579. (a) A heavy chain variable region (VH) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 50, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 156, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 262, and (b) A light chain variable region (VL) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 368, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 474, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO:

580. (a) A heavy chain variable region (VH) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 51, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 157, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 263, and (b) A light chain variable region (VL) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 369, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 475, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO:

581. (a) A heavy chain variable region (VH) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 52, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 158, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 264, and (b) A light chain variable region (VL) comprising (i) CDR1 having an amino acid sequence according to sequence number 370, (ii) CDR2 having an amino acid sequence according to sequence number 476, and (iii) CDR3 having an amino acid sequence according to sequence number 582. (a) a heavy chain variable region (VH) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 53, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 159, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 265, and (b) A light chain variable region (VL) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 371, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 477, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO:

583. (a) a heavy chain variable region (VH) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 54, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 160, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 266, and (b) A light chain variable region (VL) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 372, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 478, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO:

584. (a) a heavy chain variable region (VH) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 55, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 161, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 267, and (b) A light chain variable region (VL) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 373, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 479, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO:

585. (a) a heavy chain variable region (VH) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 56, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 162, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 268, and (b) A light chain variable region (VL) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 374, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 480, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO:

586. (a) a heavy chain variable region (VH) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 57, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 163, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 269, and (b) A light chain variable region (VL) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 375, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 481, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO:

587. (a) a heavy chain variable region (VH) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 58, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 164, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 270, and (b) A light chain variable region (VL) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 376, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 482, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO:

588. (a) a heavy chain variable region (VH) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 60, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 166, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 272, and (b) A light chain variable region (VL) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 378, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 484, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO:

590. (a) a heavy chain variable region (VH) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 61, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 167, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 273, and (b) A light chain variable region (VL) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 379, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 485, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO:

591. (a) A heavy chain variable region (VH) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 62, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 168, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 274, and (b) A light chain variable region (VL) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 380, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 486, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO:

592. (a) a heavy chain variable region (VH) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 63, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 169, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 275, and (b) A light chain variable region (VL) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 381, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 487, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO:

593. (a) a heavy chain variable region (VH) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 64, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 170, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 276, and (b) A light chain variable region (VL) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 382, ​​(ii) CDR2 having an amino acid sequence according to SEQ ID NO: 488, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO:

594. (a) a heavy chain variable region (VH) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 65, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 171, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 277, and (b) A light chain variable region (VL) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 383, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 489, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO:

595. (a) a heavy chain variable region (VH) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 66, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 172, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 278, and (b) A light chain variable region (VL) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 384, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 490, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO:

596. (a) a heavy chain variable region (VH) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 67, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 173, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 279, and (b) A light chain variable region (VL) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 385, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 491, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO:

59. (a) a heavy chain variable region (VH) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 68, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 174, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 280, and (b) A light chain variable region (VL) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 386, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 492, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO:

598. (a) A heavy chain variable region (VH) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 69, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 175, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 281, and (b) A light chain variable region (VL) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 387, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 493, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO:

599. (a) a heavy chain variable region (VH) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 70, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 176, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 282, and (b) A light chain variable region (VL) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 388, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 494, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO:

600. (a) a heavy chain variable region (VH) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 71, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 177, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 283, and (b) A light chain variable region (VL) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 389, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 495, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO:

601. (a) a heavy chain variable region (VH) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 72, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 178, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 284, and (b) A light chain variable region (VL) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 390, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 496, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO:

602. (a) A heavy chain variable region (VH) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 73, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 179, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 285, and (b) A light chain variable region (VL) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 391, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 497, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO:

603. (a) a heavy chain variable region (VH) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 74, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 180, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 286, and (b) A light chain variable region (VL) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 392, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 498, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO:

604. (a) a heavy chain variable region (VH) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 75, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 181, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 287, and (b) A light chain variable region (VL) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 393, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 499, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO:

605. (a) A heavy chain variable region (VH) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 76, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 182, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 288, and (b) A light chain variable region (VL) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 394, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 500, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO:

606. (a) a heavy chain variable region (VH) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 77, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 183, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 289, and (b) A light chain variable region (VL) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 395, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 501, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO:

607. (a) a heavy chain variable region (VH) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 78, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 184, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 290, and (b) A light chain variable region (VL) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 396, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 502, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO:

608. (a) A heavy chain variable region (VH) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 79, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 185, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 291, and (b) A light chain variable region (VL) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 397, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 503, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO:

609. (a) A heavy chain variable region (VH) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 80, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 186, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 292, and (b) A light chain variable region (VL) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 398, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 504, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO:

610. (a) a heavy chain variable region (VH) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 84, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 190, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 296, and (b) A light chain variable region (VL) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 402, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 508, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO:

614. (a) a heavy chain variable region (VH) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 85, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 191, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 297, and (b) A light chain variable region (VL) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 403, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 509, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO:

615. (a) a heavy chain variable region (VH) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 86, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 192, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 298, and (b) A light chain variable region (VL) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 404, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 510, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO:

616. (a) a heavy chain variable region (VH) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 87, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 193, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 299, and (b) A light chain variable region (VL) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 405, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 511, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO:

617. (a) a heavy chain variable region (VH) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 88, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 194, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 300, and (b) A light chain variable region (VL) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 406, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 512, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO:

618. (a) a heavy chain variable region (VH) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 89, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 195, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 301, and (b) A light chain variable region (VL) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 407, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 513, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO:

619. (a) A heavy chain variable region (VH) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 90, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 196, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 302, and (b) A light chain variable region (VL) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 408, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 514, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO:

620. (a) a heavy chain variable region (VH) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 91, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 197, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 303, and (b) A light chain variable region (VL) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 409, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 515, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO:

621. (a) a heavy chain variable region (VH) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 92, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 198, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 304, and (b) A light chain variable region (VL) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 410, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 516, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO:

622. (a) a heavy chain variable region (VH) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 93, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 199, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 305, and (b) A light chain variable region (VL) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 411, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 517, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO:

623. (a) a heavy chain variable region (VH) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 94, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 200, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 306, and (b) A light chain variable region (VL) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 412, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 518, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO:

624. (a) a heavy chain variable region (VH) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 95, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 201, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 307, and (b) A light chain variable region (VL) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 413, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 519, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO:

625. (a) a heavy chain variable region (VH) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 96, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 202, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 308, and (b) A light chain variable region (VL) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 414, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 520, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO:

626. (a) a heavy chain variable region (VH) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 97, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 203, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 309, and (b) A light chain variable region (VL) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 415, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 521, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO:

627. (a) a heavy chain variable region (VH) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 98, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 204, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 310, and (b) A light chain variable region (VL) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 416, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 522, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO:

628. (a) a heavy chain variable region (VH) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 99, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 205, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 311, and (b) A light chain variable region (VL) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 417, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 523, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO:

629. (a) a heavy chain variable region (VH) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 100, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 206, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 312, and (b) A light chain variable region (VL) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 418, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 524, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO:

630. (a) A heavy chain variable region (VH) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 101, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 207, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 313, and (b) A light chain variable region (VL) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 419, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 525, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO:

631. (a) a heavy chain variable region (VH) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 102, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 218, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 314, and (b) A light chain variable region (VL) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 420, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 526, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO:

632. (a) A heavy chain variable region (VH) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 103, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 209, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 315, and (b) A light chain variable region (VL) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 421, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 527, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO:

633. (a) A heavy chain variable region (VH) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 104, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 210, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 316, and (b) A light chain variable region (VL) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 422, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 528, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO:

634. (a) a heavy chain variable region (VH) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 105, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 211, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 317, and (b) A light chain variable region (VL) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 423, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 529, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 635, or (a) a heavy chain variable region (VH) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 106, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 212, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 318, and (b) A light chain variable region (VL) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 424, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 530, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO:

636. An α4β7 binding protein containing this protein.

2. below: a) A heavy chain variable region (VH) comprising (i) CDR1 having an amino acid sequence following any one of SEQ ID NOs: 7-26, 32-58, 60-80, and 84-106; (ii) CDR2 having an amino acid sequence following any one of SEQ ID NOs: 113-132, 138-164, 166-186, and 190-212; and (iii) CDR3 having an amino acid sequence following any one of SEQ ID NOs: 219-238, 244-270, 272-292, and 296-318; and b) Light chain variable region (VL) comprising (i) CDR1 having an amino acid sequence following any one of SEQ ID NOs: 325-344, 350-376, 378-398, and 402-424; (ii) CDR2 having an amino acid sequence following any one of SEQ ID NOs: 431-450, 456-482, 484-504, and 508-530; and (iii) CDR3 having an amino acid sequence following any one of SEQ ID NOs: 537-556, 562-588, 590-610, and 614-636. An α4β7 binding protein containing this protein.

3. The α4β7 binding protein according to claim 1 or claim 2, wherein the VH comprises a sequence having at least 80% sequence identity with respect to any one of the amino acid sequences among sequence numbers 1915-1934, 1940-1966, 1968-1988, and 1992-2014, and the VL comprises a sequence having at least 80% sequence identity with respect to any one of the amino acid sequences among sequence numbers 2021-2040, 2046-2072, 2074-2094, and 2098-2120.

4. The VH comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1915, and the VL comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2021. The VH comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1916, and the VL comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2022. The VH comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1917, and the VL comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2023. The VH comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1918, and the VL comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2024. The VH comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1919, and the VL comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2025. The VH comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1920, and the VL comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2026. The VH comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1921, and the VL comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2027. The VH comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1922, and the VL comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2028. The VH comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1923, and the VL comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2029. The VH comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1924, and the VL comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2030. The VH comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1925, and the VL comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2031. The VH comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1926, and the VL comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2032. The VH comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1927, and the VL comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2033. The VH comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1928, and the VL comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2034. The VH comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1929, and the VL comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2035. The VH comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1930, and the VL comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2036. The VH comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1931, and the VL comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2037. The VH comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1932, and the VL comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2038. The VH comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1933, and the VL comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2039. The VH comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1934, and the VL comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2040. The VH comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1940, and the VL comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2046. The VH comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1941, and the VL comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2047. The VH comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1942, and the VL comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2048. The VH comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1943, and the VL comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2049. The VH comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1944, and the VL comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2050. The VH comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1945, and the VL comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2051. The VH comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1946, and the VL comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2052. The VH comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1947, and the VL comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2053. The VH comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1948, and the VL comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2054. The VH comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1949, and the VL comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2055. The VH comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1950, and the VL comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2056. The VH comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1951, and the VL comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2057. The VH comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1952, and the VL comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2058. The VH comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1953, and the VL comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2059. The VH comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1954, and the VL comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2060. The VH comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1955, and the VL comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2061. The VH comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1956, and the VL comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2062. The VH comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1957, and the VL comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2063. The VH comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1958, and the VL comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2064. The VH comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1959, and the VL comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2065. The VH comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1960, and the VL comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2066. The VH comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1961, and the VL comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2067. The VH comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1962, and the VL comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2068. The VH comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1963, and the VL comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2069. The VH comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1964, and the VL comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2070. The VH comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1965, and the VL comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2071. The VH comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1966, and the VL comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2072. The VH comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1968, and the VL comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2074. The VH comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1969, and the VL comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2075. The VH comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1970, and the VL comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2076. The VH comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1971, and the VL comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2077. The VH comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1972, and the VL comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2078. The VH comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1973, and the VL comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2079. The VH comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1974, and the VL comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2080. The VH comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1975, and the VL comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2081. The VH comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1976, and the VL comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2082. The VH comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1977, and the VL comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2083. The VH comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1978, and the VL comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2084. The VH comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1979, and the VL comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2085. The VH comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1980, and the VL comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2086. The VH comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1981, and the VL comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2087. The VH comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1982, and the VL comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2088. The VH comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1983, and the VL comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2089. The VH comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1984, and the VL comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2090. The VH comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1985, and the VL comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2091. The VH comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1986, and the VL comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2092. The VH comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1987, and the VL comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2093. The VH comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1992, and the VL comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2098. The VH comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1993, and the VL comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2099. The VH comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1994, and the VL comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2100. The VH comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1995, and the VL comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2101. The VH comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1996, and the VL comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2102. The VH comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1997, and the VL comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2103. The VH comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1998, and the VL comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2104. The VH comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1999, and the VL comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2105. The VH comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2000, and the VL comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2106. The VH comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2001, and the VL comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2107. The VH comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2002, and the VL comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2108. The VH comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2003, and the VL comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2109. The VH comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2004, and the VL comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2110. The VH comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2005, and the VL comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2111. The VH comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2006, and the VL comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2112. The VH comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2007, and the VL comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2113. The VH comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2008, and the VL comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2114. The VH comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2009, and the VL comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2115. The VH comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2010, and the VL comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2116. The VH comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2011, and the VL comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2117. The VH comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2012, and the VL comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2118. The VH contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2013, and the VL contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2119, or The VH comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2014, and the VL comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2120. The α4β7 binding protein according to any one of claims 1 to 3.

5. below: (a) a heavy chain variable region (VH) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 3, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 109, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 215, and (b) A light chain variable region (VL) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 321, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 427, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 533, or (a) a heavy chain variable region (VH) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 4, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 110, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 216, and (b) A light chain variable region (VL) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 322, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 428, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 534, or (a) a heavy chain variable region (VH) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 5, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 111, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 217, and (b) A light chain variable region (VL) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 323, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 429, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 535, or (a) a heavy chain variable region (VH) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 6, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 112, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 218, and (b) A light chain variable region (VL) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 324, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 430, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 536, or (a) a heavy chain variable region (VH) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 81, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 187, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 293, and (b) A light chain variable region (VL) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 399, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 505, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 611, or (a) a heavy chain variable region (VH) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 82, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 188, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 294, and (b) A light chain variable region (VL) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 400, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 506, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 612, or (a) a heavy chain variable region (VH) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 83, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 189, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO: 295, and (b) A light chain variable region (VL) comprising (i) CDR1 having an amino acid sequence according to SEQ ID NO: 401, (ii) CDR2 having an amino acid sequence according to SEQ ID NO: 507, and (iii) CDR3 having an amino acid sequence according to SEQ ID NO:

613. An α4β7 binding protein containing this protein.

6. The α4β7 binding protein according to claim 5, wherein VH contains a sequence having at least 80% sequence identity with any one of the amino acid sequences among sequence numbers 1911-1914 and 1925-1927, and VL contains a sequence having at least 80% sequence identity with any one of the amino acid sequences among sequence numbers 2017-2020 and 2031-2033.

7. The VH contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1911, and the VL contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2017, or The VH contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1912, and the VL contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2018, or The VH contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1913, and the VL contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2019, or The VH contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1914, and the VL contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2020, or The VH includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1925, and the VL includes a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2031, or The VH contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1926, and the VL contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2032, or The VH contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1927, and the VL contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2033. The α4β7 binding protein according to claim 5 or claim 6.

8. below: a) A heavy chain variable region (VH) containing an amino acid sequence that follows any one of sequence numbers 1909, 1910, 1935-1939, and 1967, and b) A light chain variable region (VL) containing an amino acid sequence that follows any one of sequence numbers 2015, 2016, 2041-2045, or 2073. An α4β7 binding protein containing this protein.

9. The VH comprises an amino acid sequence according to SEQ ID NO: 1909, and the VL comprises an amino acid sequence according to SEQ ID NO: 2015. The VH comprises an amino acid sequence according to SEQ ID NO: 1910, and the VL comprises an amino acid sequence according to SEQ ID NO: 2016. The VH comprises an amino acid sequence according to SEQ ID NO: 1935, and the VL comprises an amino acid sequence according to SEQ ID NO: 2041. The VH comprises an amino acid sequence according to SEQ ID NO: 1936, and the VL comprises an amino acid sequence according to SEQ ID NO: 2042. The VH comprises an amino acid sequence according to SEQ ID NO: 1937, and the VL comprises an amino acid sequence according to SEQ ID NO: 2043. The VH comprises an amino acid sequence according to SEQ ID NO: 1938, and the VL comprises an amino acid sequence according to SEQ ID NO: 2044. The VH comprises an amino acid sequence according to SEQ ID NO: 1939, and the VL comprises an amino acid sequence according to SEQ ID NO: 2045, or The VH comprises an amino acid sequence according to SEQ ID NO: 1967, and the VL comprises an amino acid sequence according to SEQ ID NO: 2073. The α4β7 binding protein according to claim 8.

10. An α4β7-binding protein according to any one of claims 1 to 9, comprising a modified Fc, wherein the modified Fc extends the half-life of the α4β7-binding protein compared to an α4β7-binding protein without the modified Fc.

11. α4β7 binding proteins, and the following: c) A heavy chain variable region (VH) comprising (i) CDR1 having an amino acid sequence according to any one of SEQ ID NOs: 1 to 106, (ii) CDR2 having an amino acid sequence according to any one of SEQ ID NOs: 107 to 212, and (iii) CDR3 having an amino acid sequence according to any one of SEQ ID NOs: 213 to 318. d) A light chain variable region (VL) comprising (i) CDR1 having an amino acid sequence according to any one of SEQ ID NOs: 319 to 424, (ii) CDR2 having an amino acid sequence according to any one of SEQ ID NOs: 425 to 530, and (iii) CDR3 having an amino acid sequence according to any one of SEQ ID NOs: 531 to 636, and e) A modified Fc which extends the half-life of the α4β7-binding protein compared to an α4β7-binding protein that does not contain the modified Fc. An α4β7 binding protein containing this protein.

12. The α4β7 binding protein according to claim 10 or claim 11, wherein the modified Fc comprises amino acid modified M252Y, S254T, and T256E (YTE) and / or L234A / G237A (LAGA).

13. The α4β7 binding protein according to any one of claims 10 to 12, wherein the Fc is an IgG1 immunoglobulin Fc domain, an IgG2 immunoglobulin Fc domain, or an IgG4 immunoglobulin Fc domain.

14. The α4β7-binding protein according to claim 12 or claim 13, wherein the α4β7-binding protein specifically binds to the α4β7 epitope, and the α4β7-binding protein is an antibody.

15. A method for treating an inflammatory disease in a patient requiring treatment for an inflammatory disease, comprising the step of subcutaneously or intravenously administering an effective amount of the α4β7 binding protein described in any one of claims 1 to 14 to the patient.

16. The method according to claim 15, wherein the inflammatory disease is inflammatory bowel disease.

17. The method according to claim 15, wherein the inflammatory bowel disease is Crohn's disease or ulcerative colitis.

18. The method according to any one of claims 15 to 17, wherein the administration of the α4β7 binding protein is subcutaneous.

19. The method according to any one of claims 15 to 17, wherein the administration of the α4β7 binding protein is intravenous.

20. An isolated nucleic acid encoding an α4β7 binding protein according to any one of claims 1 to 14.

21. Recombinant host cells comprising isolated nucleic acids as described in claim 20.

22. A pharmaceutical composition comprising an effective amount of the α4β7 binding protein described in any one of claims 1 to 14 and a pharmaceutically acceptable carrier.