Alpha4beta7 integrin binding proteins and methods of use

Abstract

Provided herein are [alpha] 4 [beta] 7 binding proteins (e.g., antibodies that bind [alpha] 4 [beta] 7) and methods of use.

Description

Cross-reference to related applications

[0001] This application claims the benefit and priority of U.S. Provisional Application No. 63 / 519,483, filed August 14, 2023, the entire contents of which are incorporated herein by reference. sequence list

[0002] This application contains a sequence list that has been filed electronically in XML format and is hereby incorporated by reference in its entirety. The XML copy created on August 11, 2024 is named 220703-010301_PCT_SL.xml and has a size of 1,927,096 bytes. Background Technology

[0003] Integrins are transmembrane receptors for cell adhesion, acting as extracellular matrix (ECM)-cytoskeleton junctions and transducers of biochemical and mechanochemical signals between the cell and its 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 the treatment of various diseases, including cancer and inflammatory diseases (e.g., inflammatory bowel disease). However, given the important roles of integrins in biological processes, current integrin therapies are accompanied by serious side effects and / or require multiple and frequent doses to maintain therapeutic efficacy. Therefore, there is a need for improved α4β7 integrin therapies. Summary of the Invention

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

[0005] In some embodiments, VH comprises a sequence having at least 80% sequence identity with any one of the amino acid sequences of SEQ ID NO: 1911-1914 and 1925-1927; and VL comprises a sequence having at least 80% sequence identity with any one of the amino acid sequences of SEQ ID NO: 2017-2020 and 2031-2033.

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

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

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

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

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

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

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

[0013] In some embodiments, an α4β7-binding protein is described herein comprising: a) a heavy chain variable region (VH), the heavy chain variable region comprising (i) a CDR1 having an amino acid sequence according to any one of SEQ ID NO: 7-26, 32-58, 60-80, and 84-106; (ii) a CDR2 having an amino acid sequence according to any one of SEQ ID NO: 113-132, 138-164, 166-186, and 190-212; and (iii) a CDR3 having an amino acid sequence according to any one of SEQ ID NO: 219-238, 244-270, 272-292, and 296-318; and b) a light chain variable region (VL), the light chain variable region comprising (i) a CDR1 having an amino acid sequence according to any one of SEQ ID NO: 7-26, 32-58, 60-80, and 84-106; and (iii) a CDR3 having an amino acid sequence according to any one of SEQ ID NO: 7-26, 32-58, 60-80, and 84-106; and (iv) a light chain variable region comprising (i) a CDR1 having an amino acid sequence according to any one of SEQ ID NO: 7-26, 32-58, 60-80, and 84-106; and (viii) a CDR3 ... (ii) CDR1 having an amino acid sequence according to any one of SEQ ID NO: 431-450, 456-482, 484-504, and 508-530; and (iii) CDR3 having an amino acid sequence according to any one of SEQ ID NO: 537-556, 562-588, 590-610, and 614-636.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

[0104] In some embodiments, VH comprises a sequence having at least 80% sequence identity with the amino acid sequence of any one of SEQ ID NO: 1915-1934, 1940-1966, 1968-1988, and 1992-2014; and VL comprises a sequence having at least 80% sequence identity with the amino acid sequence of any one of SEQ ID NO: 2021-2040, 2046-2072, 2074-2094, and 2098-2120.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

[0196] In some embodiments, this document describes an α4β7 binding protein comprising: a) a heavy chain variable region (VH) comprising an amino acid sequence according to any one of SEQ ID NO: 1909, 1910, 1935-1939, 1967; and b) a light chain variable region (VL) comprising an amino acid sequence according to any one of SEQ ID NO: 2015, 2016, 2041-2045, 2073.

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

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

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

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

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

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

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

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

[0205] In some embodiments, this document describes an α4β7 binding protein comprising: a) a heavy chain variable region (VH) comprising (i) CDR1 having an amino acid sequence according to any one of SEQ ID NO: 1-106, (ii) CDR2 having an amino acid sequence according to any one of SEQ ID NO: 107-212, and (iii) CDR3 having an amino acid sequence according to any one of SEQ ID NO: 213-318; b) a light chain variable region (VL) comprising (i) CDR1 having an amino acid sequence according to any one of SEQ ID NO: 319-424, (ii) CDR2 having an amino acid sequence according to any one of SEQ ID NO: 425-530, and (iii) CDR3 having an amino acid sequence according to any one of SEQ ID NO: 531-636; and c) The modified Fc comprises amino acid modifications M252Y, S254T and T256E (YTE) and / or L234A / G237A (LAGA).

[0206] In some embodiments, this document describes an α4β7 binding protein comprising: a) a heavy chain variable region (VH) comprising (i) CDR1 having an amino acid sequence according to any one of SEQ ID NO: 1-106, (ii) CDR2 having an amino acid sequence according to any one of SEQ ID NO: 107-212, and (iii) CDR3 having an amino acid sequence according to any one of SEQ ID NO: 213-318; b) a light chain variable region (VL) comprising (i) CDR1 having an amino acid sequence according to any one of SEQ ID NO: 319-424, (ii) CDR2 having an amino acid sequence according to any one of SEQ ID NO: 425-530, and (iii) CDR3 having an amino acid sequence according to any one of SEQ ID NO: 531-636; and c) The modified Fc, compared to the α4β7 binding protein without the modified Fc, prolongs the half-life of the α4β7 binding protein.

[0207] In some embodiments, this document describes an α4β7 binding protein that specifically binds to the epitope of α4β7 and comprises an Fc domain containing amino acid modifications of M252Y, S254T, and T256E (YTE) and / or L234A / G237A (LAGA).

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

[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] This disclosure relates to compositions comprising the α4β7-binding protein described herein and a pharmaceutically acceptable carrier. This document also provides injectable liquid compositions comprising the α4β7-binding protein described herein and a pharmaceutically acceptable carrier.

[0214] This disclosure relates to nucleic acids encoding the α4β7-binding protein described herein. In some embodiments, this document provides recombinant host cells containing nucleic acids encoding the α4β7-binding protein described herein.

[0215] This disclosure relates to a method of treating inflammatory bowel disease in a patient in need, the method comprising administering an effective amount of the α4β7-binding protein described herein subcutaneously or intravenously 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] This disclosure relates to a method of treating an inflammatory disease in a patient in need, the method comprising administering an effective amount of the α4β7-binding protein described herein subcutaneously or intravenously 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. Attached Figure Description

[0217] Figure 1Binding curves of anti-α4β7 comparative antibody, control anti-α4 antibody, and exemplary antibodies (antibody 1 and antibody 2) as concentration increase were plotted after incubation with the RPMI-8866 cell line expressing only α4β7 integrin, as determined by flow cytometry analysis. The x-axis depicts antibody concentration in nanomolar (nM), while the y-axis depicts cell binding as mean fluorescence intensity (MFI).

[0218] Figure 2 Binding curves of the anti-α4β7 comparative antibody, control anti-α4 antibody, and exemplary antibodies (antibody 1 and antibody 2) as concentration increased after incubation with Ramos cell lines expressing only α4, as determined by flow cytometry analysis, were plotted. The x-axis depicts antibody concentration in nanomolar (nM), while the y-axis depicts cell binding expressed as mean fluorescence intensity (MFI).

[0219] Figure 3 The percentage of adhesion inhibition was plotted on MAdCAM-1-coated plates after mixing with HuT-78 cells expressing α4β7-integrin and α4β1-integrin, comparing the percentage of adhesion inhibition with increasing concentration of the antibody and exemplary antibodies (antibody 1 and antibody 2). The x-axis plots the antibody concentration in nanomolar (nM), while the y-axis plots the percentage of adhesion inhibition.

[0220] Figure 4 The percentage of adhesion inhibition was plotted on VCAM-1-coated plates after mixing with HuT-78 cells expressing α4β7-integrin and α4β1-integrin, comparing the percentage of adhesion inhibition with increasing concentration of antibodies, control anti-α4 antibodies, and exemplary antibodies (antibody 1 and antibody 2). The x-axis plots antibody concentration in nanomolar (nM), while the y-axis plots the percentage of adhesion inhibition. Detailed Implementation

[0221] To facilitate understanding of this disclosure, a number of terms and phrases are defined below.

[0222] As used herein, unless otherwise stated, the term "antibody" should be understood to mean an intact antibody (e.g., an intact monoclonal antibody), or a fragment thereof (such as the Fc fragment of an antibody (e.g., the Fc fragment of a monoclonal antibody)), or an antigen-binding fragment of an antibody (e.g., the antigen-binding fragment of a monoclonal antibody), including modified, engineered, or chemically conjugated intact antibodies, antigen-binding fragments, or Fc fragments. Typically, antibodies are polyproteins containing four polypeptide chains. Two polypeptide chains are called immunoglobulin heavy chains (H chains), and two 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 a variable region (VL) and a constant region (CL). The heavy chain consists of a variable region (VH) and at least three constant regions (CH1, CH2, and CH3). The variable region determines the binding specificity of the antibody. Each variable region contains three hypervariable regions (called complementarity-determining regions (CDRs)) flanked by four relatively conserved regions (called frame regions (FRs)). The ranges of FRs and CDRs have been defined (Kabat, E.A. et al. (1991) Sequences of Proteins of Immunological Interest, 5th ed., US 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 (called CDR1, CDR2, and CDR3) contribute to antibody binding specificity. Naturally occurring antibodies have been used as starting materials for engineered antibodies, such as chimeric and humanized antibodies. Examples of antibody-based antigen-binding fragments include Fab, Fab', (Fab')2, Fv, single-chain antibodies (e.g., scFv), microantibodies, and biantibodies. Examples of modified or engineered antibodies include chimeric antibodies, humanized antibodies, and multispecific antibodies (e.g., bispecific antibodies). Examples of chemically conjugated antibodies are antibodies conjugated with a toxic moiety.

[0223] The terms "variable domain" and "variable region" are used interchangeably and refer to portions of an antibody or immunoglobulin domain that exhibit variability in their sequence and are involved in determining the specificity and binding affinity of a particular antibody. This variability is not uniformly distributed throughout the variable domain of an antibody; it is concentrated in subdomains of each heavy and light chain variable region. 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) and provide a scaffold for the six CDRs in three-dimensional space to form an antigen-binding surface.

[0224] As used herein, the “Fc polypeptide” of a dimer Fc refers to one of two polypeptides that form the Fc domain of the dimer, namely a polypeptide containing the C-terminal constant region of the immunoglobulin heavy chain, which is capable of stable self-association. For example, the Fc polypeptide of a dimer IgG Fc contains the IgG CH2 and IgG CH3 constant domain sequences. Fc can belong to the categories IgA, IgD, IgE, IgG, and IgM. These categories are also designated as α, δ, ε, γ, and µ, respectively. Several of these can be further subdivided into subtypes (isotypes), such as 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 naturally occurring human FcR. Typically, an FcR is an FcR (γ receptor) that binds to IgG antibodies and includes receptors of the FcγRI, FcγRII, and FcγRIII subclasses (including allelic variants and alternative spliced ​​forms of these receptors). FcγRII receptors include FcγRIIA (“activating receptor”) and FcγRIIB (“inhibiting receptor”), which have similar amino acid sequences and are distinguished primarily by their cytoplasmic domains. Other isotypes of immunoglobulins may also bind to certain FcRs (see, for example, Janeway et al., Immuno Biology: the immune system in health and disease, (Elsevier Science Ltd., New York) (4th ed., 1999)). The activating receptor FcγRIIA contains an activating motif (ITAM) based on the tyrosine residue of the immune receptor in its cytoplasmic domain. The repressive receptor FcγRIIB contains an repressive motif (ITIM) based on the tyrosine residue of the immune receptor in its cytoplasmic domain (see Daëron, Annu. Rev. Immunol. [Annals of Immunology] 15:203-234 (1997)). FcRs are reviewed in Ravetch and Kinet, Annu. Rev. Immunol. [Annals of Immunology] 9:457-92 (1991); Capel et al., Immunomethods [Immunomethods] 4:25-34 (1994); and de Haas et al., J. Lab. Clin. Med. [Journal of Laboratory and Clinical Medicine] 126:330-41 (1995). The term “FcR” in this article encompasses other FcRs, including those to be identified in the future. The term also includes neonatal receptor FcRn, which is responsible for transferring maternal IgG to the fetus (Guyer et al., J. Immunol. [Journal of Immunology] 117:587 (1976); and Kim et al., J. Immunol. [Journal of Immunology] 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 requiring diagnosis, treatment, or therapy, particularly a human. “Mammalian” for therapeutic purposes means any animal classified as a mammal, including humans, livestock, and farm animals, as well as laboratory animals, zoo animals, racing animals, or pet animals, such as dogs, horses, cats, cattle, sheep, goats, pigs, mice, rats, rabbits, guinea pigs, monkeys, etc. In some embodiments, the mammal is a human. These terms do not require medical supervision.

[0227] As used herein, the term "effective amount" means an amount of compound (e.g., the compound disclosed herein) sufficient to achieve a beneficial or desired result. An effective amount may be administered in one or more doses, applications, or dosages and is not intended to be limited to a particular formulation or route of administration. As used herein, the term "treatment" includes any effect that improves a condition, disease, symptom, etc., or alleviates its symptoms, for example, by relieving, reducing, moderating, reducing, or eliminating.

[0228] As used herein, the term "pharmaceutical composition" refers to a combination of an active pharmaceutical agent and an inert or active carrier, making the composition particularly suitable for in vivo or in vitro diagnostic or therapeutic uses.

[0229] As used herein, the term "pharmaceutically acceptable carrier" refers to any standard drug carrier, such as phosphate-buffered saline solutions, water, emulsions (e.g., oil / water or water / oil emulsions), and various types of wetting agents. These compositions may also include stabilizers and preservatives. For examples of carriers, stabilizers, and adjuvants, see, for example, Martin, Remington's Pharmaceutical Sciences, 15th edition, Mack Publ. Co., Easton, Pennsylvania (1975).

[0230] Unless the context is inappropriate, as used herein, the term "a / species (a and an)" means "one / species or more / species" and includes the plural.

[0231] As used herein, unless the context explicitly indicates otherwise, all numerical values ​​or ranges of values ​​include integers that fall within or encompass such ranges, and fractions of values ​​or integers that fall within or encompass such ranges. Thus, for example, references to a range of 90%–100% include 91%, 92%, 93%, 94%, 95%, 95%, 96%, 97%, etc., and 91.1%, 91.2%, 91.3%, 91.4%, 91.5%, etc., 92.1%, 92.2%, 92.3%, 92.4%, 92.5%, etc., and so on. In another example, the range of 1-5,000 times includes 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, and so on.

[0232] As used herein, “about” a value means a range that includes the value and that range is from 10% below the value to 10% above the value. “About” a range means from 10% below the lower limit of the range to 10% above the upper limit of the range.

[0233] "Identity percentage (%)" refers to the degree to which two sequences (nucleotides or amino acids) have identical residues at the same positions in the alignment. For example, "the amino acid sequence is X% identical to SEQ ID NO: Y" means that the amino acid sequence is % identical to SEQ ID NO: Y, and states that X% of the residues in the amino acid sequence are identical to the residues in the sequence disclosed in SEQ ID NO: Y. Typically, such calculations are performed using computer programs. Exemplary programs for comparing and aligning sequence pairs include ALIGN (Myers and Miller, 1988), FASTA (Pearson and Lipman, 1988; Pearson, 1990), and vacancy BLAST (Altschul et al., 1997), BLASTP, BLASTN, or GCG (Devereux et al., 1984).

[0234] Throughout this specification, where compositions are described as having, including, or comprising specific components, or where processes and methods are described as having, including, or comprising specific steps, the existence of compositions of this disclosure that are substantially composed of or constituted by the listed components is also contemplated, as are processes and methods of this disclosure that are substantially composed of or constituted by the listed processing steps.

[0235] Generally, unless otherwise specified, specified percentages of compositions are by weight. Additionally, if a variable is not defined, its previously defined meaning shall prevail. α4β7 integrin-binding protein

[0236] This document provides an α4β7 integrin-binding protein. In some embodiments, the α4β7 integrin-binding protein is an antibody. In some embodiments, the α4β7 integrin-binding protein comprises a modified Fc that prolongs the half-life of the α4β7-binding protein compared to an α4β7-binding protein without said modified Fc.

[0237] In some embodiments, this document further describes an α4β7 integrin-binding protein, wherein the α4β7-binding protein specifically binds to the epitope of α4β7 and comprises an Fc domain containing amino acid modifications of M252Y, S254T, and T256E (YTE) and / or L234A / G237A (LAGA).

[0238] The amino acid sequences of exemplary CDRs of α4β7 integrin-binding proteins are provided in Table 1.

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

[0240] In some embodiments, the α4β7 integrin-binding protein includes a light chain variable region, which includes 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 NO: 1-106, (b) a CDR2 having an amino acid sequence according to any one of SEQ ID NO: 107-212, and (c) a CDR3 having an amino acid sequence according to any one of SEQ ID NO: 213-318. 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 NO: 319-424, (b) a CDR2 having an amino acid sequence according to any one of SEQ ID NO: 425-530, and (c) a CDR3 having an amino acid sequence according to any one of SEQ ID NO: 531-536.

[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 NO: 637-742, (b) CDR2 having an amino acid sequence according to any one of SEQ ID NO: 743-848, and (c) CDR3 having an amino acid sequence according to any one of SEQ ID NO: 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 NO: 955-1060, (b) CDR2 having an amino acid sequence according to any one of SEQ ID NO: 1061-1166, and (c) CDR3 having an amino acid sequence according to any one of SEQ ID NO: 1167-1272.

[0243] In some embodiments, the α4β7 integrin-binding protein includes a heavy chain. In some embodiments, the α4β7 integrin-binding protein includes a heavy chain variable region, the heavy chain variable region comprising (a) CDR1 having an amino acid sequence according to any one of SEQ ID NO: 1273-1378, (b) CDR2 having an amino acid sequence according to any one of SEQ ID NO: 1378-1484, and (c) CDR3 having an amino acid sequence according to any one of SEQ ID NO: 1485-1590. In some embodiments, the α4β7 integrin-binding protein includes a light chain variable region, the light chain variable region comprising (a) CDR1 having an amino acid sequence according to any one of SEQ ID NO: 1591-1696, (b) CDR2 having an amino acid sequence according to any one of GIS, YIS, FIS, and PIS, and (c) CDR3 having an amino acid sequence according to any one of SEQ ID NO: 1803-1908.

[0244] The amino acid sequences of exemplary heavy chain variable regions (VH) and light chain variable regions (VL) of α4β7 integrin-binding proteins are provided in Table 2. Table 2. Sequences of the heavy chain variable region (VH) and light chain variable region (VL) of the α4β7 integrin-binding protein.

[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%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity with the amino acid sequences listed in Table 2.

[0246] In some embodiments, the α4β7 integrin-binding protein comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the heavy chain variable region comprises 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%) of the heavy chain variable region (VH) of the α4β7 integrin-binding protein disclosed in Table 2, and the light chain variable region comprises 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%) of the light chain variable region (VL) of the same α4β7 integrin-binding protein disclosed in Table 2. Fc modification

[0247] This article describes α4β7 integrin-binding proteins containing modified Fc regions. Unless otherwise stated herein, the amino acid residues in the Fc or constant regions are numbered according to the EU numbering system, also known as the EU index, as described in Kabat et al., Sequences of Proteins of Immunological Interest, 5th Edition, Public Health Service, National Institutes of Health, Bethesda, MD, 1991.

[0248] In some embodiments, the α4β7 integrin-binding protein comprises a modified Fc, said modified Fc containing one or more modifications. In some embodiments, the one or more modifications are located in the Fc from IgG1 (e.g., human IgG1 (hIgG1)). In some embodiments, the one or more modifications are located in the Fc from IgG4 (e.g., human IgG4 (hIgG4)). In some embodiments, the one or more modifications are located in the Fc from IgG2. In some embodiments, the one or more modifications promote selective binding to the Fc-γ receptor.

[0249] The amino acid sequences of exemplary Fc sequences are provided in Table 3. Table 3. Fc sequences

[0250] In some embodiments, the α4β7 integrin-binding protein comprises Fc, wherein the Fc has an amino acid sequence having a terminal lysine compared to any one of SEQ ID NO: 2121, 2123, 2126-2152, 2162-2164, 2166-2222, 2226-2232. In some embodiments, the α4β7 integrin-binding protein comprises Fc, wherein the Fc has an amino acid sequence lacking a terminal lysine compared to any one of SEQ ID NO: 2122, 2124, 2125, 2153-2161, 2165, 2223-2225.

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

[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 comprises a specific combination 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] In some embodiments, the modified Fc comprises a specific combination of amino acid substitutions selected from the group consisting of: M428L / N434S (LS); M252Y / S254T / T256E (YTE); T250Q / M428L; T307A / E380A / N434A; T256D / T307Q (DQ); T256D / T307W (DW); M252Y / T256D (YD); T307Q / Q311V / A378V (QVV); T256D / H285D / T307R / Q311V / A378V (DDRVV); L309D / Q311H / N434S (DHS); S228P / L235E (S PLE); L234A / L235A (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 / DH S; LAGA / DHS; LALAGA / DHS; LALAPG / DHS; SP / YTE; SPLE / YTE; SP / LS; SPLE / LS; SP / DHS; SPLE / DHS; ALAPG / LA; N297A / N434A; D265A / N434A; LALA / N434A; LAGA / N434A; LALAGA / N434A; LALAPG / N434A; N297A / N434W; D265A / N434W; LALA / N434W; LAGA / N434 W;LALAGA / N434W;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;N297A / YD;D265A / YD;LALA / YD;LAGA / YD;LALAGA / YD;LALAPG / YD;N297A / QVV;D265A / QVV;LALA / QVV;LAGA / QVV,LALAGA / QVV;LALAPG / QVV;N297A / DDRVV; 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 comprises a specific combination of amino acid substitutions selected from the group consisting of M428L / N434S (LS) and M252Y / S254T / T256E (YTE). In some embodiments, the modified Fc comprises the modification M428L / N434S(LS) (e.g., SEQ ID NO: 2139, SEQ ID NO: 2156, SEQ ID NO: 2163). In some embodiments, the modified Fc comprises the modification M252Y / S254T / T256E(YTE) (e.g., SEQ ID NO: 2132, SEQ ID NO: 2153, SEQ ID NO: 2162).

[0255] In some embodiments, the α4β7 integrin-binding protein described herein includes modifications that enhance its ability to mediate effector function. Such modifications are known in the art and include defucosylation or engineering of Fc affinity for activating receptors (primarily FCGR3a, for antibody-dependent cytotoxicity (ADCC)) and for C1q (for complement-dependent cytotoxicity (CDC)).

[0256] In some respects, the antibodies presented herein comprise an Fc domain (e.g., IgG1) with a reduced fucose content at position Asn 297 (EU number) compared to the naturally occurring Fc domain. Such Fc domains are known to have improved ADCC. In some respects, such antibodies do not contain any fucose at position Asn 297.

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

[0258] In some embodiments, Fc comprises an amino acid sequence having at least 80% sequence identity with the amino acid sequence of any one of SEQ ID NO: 2124-2232. In some embodiments, Fc comprises an amino acid sequence having at least 85% sequence identity with the amino acid sequence of any one of SEQ ID NO: 2124-2232. In some embodiments, Fc comprises an amino acid sequence having at least 90% sequence identity with the amino acid sequence of any one of SEQ ID NO: 2124-2232. In some embodiments, Fc comprises an amino acid sequence having at least 95% sequence identity with the amino acid sequence of any one of SEQ ID NO: 2124-2232. In some embodiments, Fc comprises an amino acid sequence having at least 96% sequence identity with the amino acid sequence of any one of SEQ ID NO: 2124-2232. In some embodiments, Fc comprises an amino acid sequence having at least 97% sequence identity with the amino acid sequence of any one of SEQ ID NO: 2124-2232. In some embodiments, Fc comprises an amino acid sequence having at least 98% sequence identity with the amino acid sequence of any one of SEQ ID NO: 2124-2232. In some embodiments, Fc comprises an amino acid sequence having at least 99% sequence identity with the amino acid sequence of any one of SEQ ID NO: 2124-2232. In some embodiments, Fc comprises an amino acid sequence of any one of SEQ ID NO: 2124-2232.

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

[0260] In some embodiments, the α4β7 integrin-binding protein described herein includes one or more alterations that improve or reduce C1q binding and / or CDC.

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

[0262] In some embodiments, the Fc region contains one or more amino acid substitutions, wherein the one or more substitutions result in a reduction of one or more of ADCC activity, ADCP activity, or CDC activity compared to an Fc without said one or more substitutions.

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

[0264] In some embodiments, the α4β7 integrin-binding protein described herein has an extended half-life (i.e., serum half-life). In some embodiments, the α4β7 integrin-binding protein described herein has a half-life of at least about 14, 28, 42, 56, 70, 84, 96, or more than 96 weeks. In some embodiments, the α4β7 integrin-binding protein described herein has a half-life in the following ranges: about 14 days to about 96 days, about 14 days to about 84 days, about 14 days to about 70 days, about 14 days to about 56 days, about 14 days to about 42 days, about 14 days to about 28 days, about 28 days to about 96 days, about 28 days to about 84 days, about 28 days to about 70 days, about 28 days to about 56 days, about 28 days to about 42 days, about 42 days to about 96 days, about 42 days to about 84 days, about 42 days to about 70 days, about 42 days to about 56 days, about 56 days to about 96 days, about 56 days to about 84 days, about 56 days to about 70 days, about 70 days to about 96 days, about 70 days to about 84 days, or about 84 days to about 96 days. In some embodiments, the α4β7 integrin-binding protein described herein includes a half-life in the range of about 42 days to about 56 days. In some embodiments, the α4β7 integrin-binding protein described herein has a half-life of at least about 50 days. Methods for measuring the 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 the comparative antibody. In some embodiments, the comparative antibody comprises the same complementarity-determining region and variable region but different Fc regions. 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 the comparative antibody. In some embodiments, the half-life of the α4β7 integrin-binding protein described herein is at least 2, at least 3, at least 4, at least 5, at least 6, at least 7, at least 8, at least 9, or at least 10 times longer than that of the comparative antibody. Treatment

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

[0267] In some embodiments, this document further describes a method of treating inflammatory bowel disease in a patient in need, the method comprising administering, subcutaneously or intravenously, an effective amount of α4β7 integrin-binding protein to the patient, the α4β7 integrin-binding protein comprising: a) a heavy chain variable region (VH), the heavy chain variable region comprising (i) a CDR1 having an amino acid sequence according to any one of SEQ ID NO: 7-26, 32-58, 60-80, and 84-106; (ii) a CDR2 having an amino acid sequence according to any one of SEQ ID NO: 113-132, 138-164, 166-186, and 190-212; and (iii) a CDR3 having an amino acid sequence according to any one of SEQ ID NO: 219-238, 244-270, 272-292, and 296-318; and b) a light chain variable region (VL), the light chain variable region comprising (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 7-26, 32-58, 60-80, and 84-106; and (iii) a CDR3 having an amino acid sequence according to any one of SEQ ID NO: 7-26, 32-58, 60-80, and 84-106; and (iv) a light chain variable region (VL), the light chain variable region comprising (i) a CDR1 having an amino acid sequence according to any one of SEQ ID NO: 7-26, 32-58, 60-80, and 84-106; and (iv) a CDR2 having an amino acid sequence according to any one of SEQ ID NO: 7-26, 32-58, 60-80, and 84-106; and (viii) a CDR3 CDR1 having an amino acid sequence according to any one of SEQ ID NO: 325-344, 350-376, 378-398 and 402-424; (ii) CDR2 having an amino acid sequence according to any one of SEQ ID NO: 431-450, 456-482, 484-504 and 508-530; and (iii) CDR3 having an amino acid sequence according to any one of SEQ ID NO: 537-556, 562-588, 590-610 and 614-636.

[0268] In some embodiments, this document further describes a method of treating inflammatory bowel disease in a patient in need, the method comprising administering, subcutaneously or intravenously, an effective amount of α4β7 integrin-binding protein to the patient, the α4β7 integrin-binding protein comprising: a) a heavy chain variable region (VH) comprising an amino acid sequence according to any one of SEQ ID NO: 1909, 1910, 1935-1939, 1967; and b) a light chain variable region (VL) comprising an amino acid sequence according to any one of SEQ ID NO: 2015, 2016, 2041-2045, 2073.

[0269] In some embodiments, this document further describes a method of treating inflammatory bowel disease in a patient in need, the method comprising administering, subcutaneously or intravenously, an effective amount of the α4β7 integrin-binding protein as described above to the patient, the α4β7 integrin-binding protein comprising: a) a heavy chain variable region (VH), the heavy chain variable region comprising (i) a CDR1 having an amino acid sequence according to any one of SEQ ID NO: 1-106, (ii) a CDR2 having an amino acid sequence according to any one of SEQ ID NO: 107-212, and (iii) a CDR3 having an amino acid sequence according to any one of SEQ ID NO: 213-318; b) a light chain variable region (VL), the light chain variable region comprising (i) a CDR1 having an amino acid sequence according to any one of SEQ ID NO: 319-424, (ii) a CDR2 having an amino acid sequence according to any one of SEQ ID NO: 425-530, and (iii) a CDR3 having an amino acid sequence according to any one of SEQ ID NO: 107-212 ... CDR3 of any of the amino acid sequences 531-636; and c) modified Fc, wherein the modified Fc comprises amino acid modifications M252Y, S254T and T256E (YTE) and / or L234A / G237A (LAGA).

[0270] In some embodiments, this document further describes a method for treating inflammatory bowel disease in patients in need, the method comprising administering, subcutaneously or intravenously, an effective amount of α4β7 integrin-binding protein to the patient, the α4β7 integrin-binding protein comprising a modified Fc that prolongs the half-life of the α4β7 binding protein compared to α4β7 binding protein without the modified Fc.

[0271] In some embodiments, this document further describes a method for treating inflammatory bowel disease in patients in need, the method comprising administering an effective amount of α4β7 integrin-binding protein subcutaneously or intravenously to the patient, wherein the α4β7-binding protein specifically binds to the epitope of α4β7 and comprises an Fc domain containing amino acid modifications of 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, α4β7 integrin-binding protein is administered intravenously, intratumorally, intramuscularly, subcutaneously, intralesionally, intraenterically, intracolonally, intrarectally, intra-intrapouchically, or intraperitoneally. In some embodiments, α4β7 integrin-binding protein is administered via a parenteral route, such as intravenously, intramuscularly, subcutaneously, intra-arterially, or intraperitoneally. In some embodiments, α4β7 integrin-binding protein is administered intravenously or subcutaneously. In some embodiments, α4β7 integrin-binding protein is administered intravenously. In some embodiments, α4β7 integrin-binding protein is administered subcutaneously.

[0274] The administration of α4β7 integrin-binding protein can be carried out at different intervals and at different doses. Pharmaceutical Composition

[0275] This disclosure is further characterized by a pharmaceutical composition containing a therapeutically effective amount of the α4β7 integrin-binding protein described herein. The composition can be formulated for use in a variety of drug delivery systems. One or more physiologically acceptable excipients or carriers may also be included in the composition for use in appropriate formulations. Suitable formulations for use in this disclosure can be found in Remington's Pharmaceutical Sciences, Mack Publishing Company, Philadelphia, PA, 17th edition, 1985. For a brief overview of drug delivery methods, see, for example, Langer (Science 249:1527-1533, 1990).

[0276] In some embodiments, the pharmaceutical composition may contain formulation materials for altering, maintaining, or preserving, for example, the composition's pH, osmotic pressure, viscosity, transparency, color, isotonicity, odor, sterility, stability, dissolution or release rate, absorption, or permeation. In such embodiments, suitable formulation materials include, but are not limited to, amino acids (such as glycine, glutamine, asparagine, arginine, or lysine); antimicrobial agents; antioxidants (such as ascorbic acid, sodium sulfite, or sodium bisulfite); buffers (such as borates, bicarbonates, Tris-HCl, citrates, phosphates, or other organic acids); fillers (such as mannitol or glycine); chelating agents (such as ethylenediaminetetraacetic acid (EDTA)); complexing agents (such as caffeine, polyvinylpyrrolidone, β-cyclodextrin, or hydroxypropyl-β-cyclodextrin); fillers; monosaccharides; disaccharides; and other carbohydrates (such as glucose, mannose, or dextrin); proteins (serum albumin, gelatin, or immunoglobulins); colorants, flavorings, and diluents; emulsifiers; hydrophilic polymers (such as polyvinylpyrrolidone); low molecular weight peptides; salt-forming antiions (such as sodium); and preservatives (such as benzene). Ingredients include: zafyl chloride, benzoic acid, salicylic acid, thimerosal, phenethyl alcohol, methylparaben, propylparaben, chlorhexidine, sorbic acid, or hydrogen peroxide; solvents (such as glycerol, propylene glycol, or polyethylene glycol); sugar alcohols (such as mannitol or sorbitol); suspending agents; surfactants or wetting agents (such as pluronics, PEG, dehydrated sorbitol esters, polysorbate esters (such as polysorbate 20, polysorbate esters), triton, tromethamine, lecithin, cholesterol, tyloxapal); stability enhancers (such as sucrose or sorbitol); tension enhancers (such as alkali metal halides (preferably sodium chloride or potassium chloride), mannitol, sorbitol); delivery media; diluents; excipients and / or adjuvants (see Remington's Pharmaceutical). Sciences [Remington Pharmaceutical Sciences], 18th edition (Mack Publishing Company, 1990).

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

[0278] In some embodiments, the pharmaceutical composition may contain nanoparticles (e.g., polymer nanoparticles), liposomes, or micelles.

[0279] In some embodiments, the pharmaceutical composition may contain a sustained-release or controlled-release formulation. Techniques for formulating sustained-release or controlled-release formulations, such as liposome carriers, bio-erosive microparticles or porous beads, and reservoir-type injections, are also known to those skilled in the art. Sustained-release formulations may include, for example, porous polymer microparticles or a semi-permeable polymer matrix in the form of a molded article (e.g., a membrane or microcapsule). Sustained-release matrices may include polyesters, hydrogels, polylactide, copolymers of L-glutamic acid and L-glutamic acid-γ-ethyl ester, poly(2-hydroxyethyl-methacrylate), ethylene vinyl acetate, or poly-D(-)-3-hydroxybutyric acid. Sustained-release compositions may also include liposomes prepared by any of several methods known in the art.

[0280] Pharmaceutical compositions containing the α4β7 integrin-binding protein disclosed herein may be provided in dose units and may be prepared by any suitable method. The pharmaceutical composition shall be formulated to be compatible with its 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 using methods known in the pharmaceutical field. See, for example, Remington's Pharmaceutical Sciences, 18th edition (Mack Publishing Company, 1990). Components suitable for parenteral administration include sterile diluents such as water for injection, saline solutions, fixed oils, polyethylene glycol, glycerol, 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 acetates, citrates, or phosphates; and agents for tonication such as sodium chloride or dextran. In some embodiments, formulations for parenteral administration do not contain citrates.

[0282] For intravenous or subcutaneous administration, suitable carriers include physiological saline, antibacterial aqueous solution, Cremophor EL™ (BASF, Pasipony, NJ), or phosphate-buffered saline (PBS). The carrier should be stable under manufacturing and storage conditions and should be resistant to microorganisms. The carrier can be a solvent or dispersion medium containing, for example, water, ethanol, polyols (e.g., glycerol, propylene glycol, and liquid polyethylene glycol), and suitable mixtures thereof.

[0283] Intravenous or subcutaneous drug delivery formulations may be contained in syringes, pens, or pouches. In some embodiments, the pouch is connected to a channel containing tubing and / or a needle. In some embodiments, the formulation is a lyophilized formulation or a liquid formulation. In some embodiments, the formulation is an injectable liquid formulation. Various devices can be used to deliver liquid formulations via the subcutaneous administration route, including on-body infusion devices, autoinjector devices, pre-filled syringes, and syringes. Typically, administration time depends on volume and device and can range from seconds to minutes.

[0284] These compositions can be sterilized using conventional sterilization techniques or by aseptic filtration. The resulting aqueous solution can be packaged for use as is or lyophilized, with the lyophilized formulation combined with a sterile aqueous carrier prior to application.

[0285] Polyols (which act as tonicators and can stabilize α4β7 integrin-binding proteins) may also be included in the formulation. The amount of polyol added to the formulation may vary depending on the desired isotonicity of the formulation. In some embodiments, aqueous formulations are isotonic. The amount of polyol added may also vary depending on the molecular weight of the polyol. For example, a lower amount of a monosaccharide (e.g., mannitol) may be added compared to a disaccharide (e.g., trehalose). In some embodiments, the polyol used as a tonicator in the formulation is mannitol.

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

[0287] In embodiments, the protein product disclosed herein is formulated as a liquid preparation. In some embodiments, the liquid preparation is prepared in combination with a sugar at a stabilization level. In some embodiments, the liquid preparation is prepared in an aqueous carrier. In some embodiments, the amount of stabilizer added is not greater than an amount that would result in a viscosity that is undesirable or inappropriate for intravenous administration. In some embodiments, the sugar is a disaccharide, such as sucrose. In some embodiments, the liquid preparation may also include one or more of a buffer, a surfactant, and a preservative.

[0288] In some embodiments, the pH of the liquid formulation is set by adding 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 in this article are pharmaceutically acceptable (safe and non-toxic for human use) and suitable for the preparation of liquid formulations. Illustrative carriers include sterile water for injection (SWFI), bacteriostatic water for injection (BWFI), pH buffers (e.g., phosphate-buffered saline), sterile saline solutions, Ringer's solution, or dextran solution.

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

[0291] α4β7 integrin-binding proteins can be lyophilized to produce lyophilized formulations comprising proteins and lyophilization protectants. The lyophilization protectant may be a sugar, such as a disaccharide. In some embodiments, the lyophilization protectant is sucrose or maltose. The lyophilized formulation may also include one or more of buffers, surfactants, fillers, and / or preservatives.

[0292] The amount of sucrose or maltose used to stabilize lyophilized pharmaceutical products can be at least a protein-to-sucrose or maltose weight ratio of 1:2. In some embodiments, the protein-to-sucrose or maltose weight ratio is 1:2 to 1:5. In some embodiments, the pH of the formulation prior to lyophilization is set by adding 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, α4β7 integrin-binding protein is administered at a uniform dose. Alternatively, the patient's dose may be adjusted based on the patient's approximate weight or surface area. Other factors for determining an appropriate dose may include the disease or condition to be treated or prevented, the severity of the disease, the route of administration, and the patient's age, sex, and medical condition. Further refinement of the estimates required to determine an appropriate therapeutic dose is routinely performed by those skilled in the art, particularly based on the dosage information and assays disclosed herein. The dose may also be determined using known assays for determining the dosage used, in conjunction with appropriate dose-response data. The dose for an individual patient may be adjusted as the disease progresses. Blood levels of the target construct or complex in the patient may be measured to see if dose adjustments are needed to achieve or maintain an effective concentration. Pharmacogenomics can be used to determine which targetable constructs and / or complexes and 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). Preparation method

[0294] The aforementioned α4β7 integrin-binding protein can be prepared using recombinant DNA techniques well known to those skilled in the art. For example, one or more separate polynucleotides encoding the α4β7 integrin-binding protein can be linked with other suitable nucleotide sequences, including, for example, constant region coding sequences and expression control sequences, to produce a conventional gene expression construct (i.e., an expression vector) encoding the desired α4β7 integrin-binding protein. The generation of the defined gene construct is within the scope of conventional techniques in this art.

[0295] Nucleic acids encoding the desired α4β7 integrin-binding protein can be introduced (ligated) into expression vectors, which can then be introduced into host cells using conventional transfection or transformation techniques. Exemplary host cells include Escherichia coli (E. coli) cells that do not normally produce IgG proteins, Chinese hamster ovary (CHO) cells, human embryonic kidney 293 (HEK 293) cells, HeLa cells, young hamster kidney (BHK) cells, monkey kidney cells (COS) cells, human hepatocellular carcinoma cells (e.g., Hep G2), and myeloma cells. Transformed host cells can be grown under conditions that allow 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, if a gene is to be expressed in *Escherichia coli*, it is first cloned into an expression vector by positioning the engineered gene downstream of a suitable bacterial promoter (e.g., Trp or Tac) and a prokaryotic signaling sequence. The expressed protein can be secreted. The expressed protein can accumulate in refractive bodies or inclusion bodies, which can be harvested after disrupting cells by Freund's crusher or sonication. The refractive bodies are then dissolved, and the protein can be refolded and / or cleaved using methods known in the art.

[0297] If the engineered gene is to be expressed in a eukaryotic host cell (e.g., CHO cells), it is first inserted into an expression vector containing a suitable eukaryotic promoter, secretion signal, poly-A sequence, and stop codon. Optionally, the vector or gene construct may contain enhancers and introns. In embodiments involving fusion proteins comprising α4β7 integrin-binding protein or a portion thereof, the expression vector optionally contains a sequence encoding all or part of a constant region, thereby enabling the expression of all or part of the heavy or light chain. The gene construct can be introduced into eukaryotic host cells using conventional techniques.

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

[0299] Following transfection, single clones can be isolated using methods known in the art, such as limiting dilution, ELISA, FACS, microscopy, or Clonepix, for cell bank generation. Clones can be cultured under conditions suitable for bioreactor scale-up and for maintaining 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 exchange chromatography, and mixed-mode chromatography. Specific embodiments

[0301] The following describes specific, non-limiting embodiments, each of which is considered to be within the scope of this disclosure. Example 1. An α4β7 binding protein, the α4β7 binding protein comprising: a) a heavy chain variable region (VH), the heavy chain variable region 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), the light chain variable region 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) a CDR1 having an amino acid sequence according to SEQ ID NO: 4, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 110, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 216; and a light chain variable region (VL), comprising (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 322, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 428, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 534; c) a heavy chain variable region (VH), the heavy chain variable region 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), the light chain variable region 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) Heavy chain variable region (VH), the heavy chain variable region 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 light chain variable region (VL), the light chain variable region 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), the heavy chain variable region 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), the light chain variable region 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 the amino acid sequence according to SEQ ID NO: 82, (ii) CDR2 having the amino acid sequence according to SEQ ID NO: 188, and (iii) CDR3 having the amino acid sequence according to SEQ ID NO: 294; and a light chain variable region (VL), comprising (i) CDR1 having the amino acid sequence according to SEQ ID NO: 400, (ii) CDR2 having the amino acid sequence according to SEQ ID NO: 506, and (iii) CDR3 having the amino acid sequence according to SEQ ID NO: 612; or g) A heavy chain variable region (VH), comprising (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 83, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 189, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 295; and a light chain variable region (VL), comprising (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 401, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 507, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 613. Example 2. The α4β7 binding protein as described in Example 1, wherein the VH comprises a sequence having at least 80% sequence identity with any one of the amino acid sequences of SEQ ID NO: 1911-1914 and 1925-1927; and the VL comprises a sequence having at least 80% sequence identity with any one of the amino acid sequences of SEQ ID NO: 2017-2020 and 2031-2033. Example 3. The α4β7 binding protein as described in Example 2, wherein the VH comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1911, and the VL comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2017. Example 4. The α4β7 binding protein as described in Example 2, wherein the VH comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1912, and the VL comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2018. Example 5. The α4β7 binding protein as described in Example 2, wherein the VH comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1913, and the VL comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2019. Example 6. The α4β7 binding protein as described in Example 2, wherein the VH comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1914, and the VL comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2020. Example 7. The α4β7 binding protein as described in Example 2, wherein 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. Example 8. The α4β7 binding protein as described in Example 2, wherein 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. Example 9. The α4β7 binding protein as described in Example 2, wherein 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. Example 10. An α4β7 binding protein, said α4β7 binding protein comprising: a) a heavy chain variable region (VH), the heavy chain variable region comprising (i) CDR1 having an amino acid sequence according to any one of SEQ ID NO: 7-26, 32-58, 60-80, and 84-106; (ii) CDR2 having an amino acid sequence according to any one of SEQ ID NO: 113-132, 138-164, 166-186, and 190-212; and (iii) CDR3 having an amino acid sequence according to any one of SEQ ID NO: 219-238, 244-270, 272-292, and 296-318; and b) A light chain variable region (VL) comprising (i) a CDR1 having an amino acid sequence according to any one of SEQ ID NO: 325-344, 350-376, 378-398 and 402-424; (ii) a CDR2 having an amino acid sequence according to any one of SEQ ID NO: 431-450, 456-482, 484-504 and 508-530; and (iii) a CDR3 having an amino acid sequence according to any one of SEQ ID NO: 537-556, 562-588, 590-610 and 614-636. Example 11. The α4β7 binding protein as described in Example 10, wherein the VH comprises (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 comprises (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. Example 12. The α4β7 binding protein as described in Example 10, wherein the VH comprises (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 comprises (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. Example 13. The α4β7 binding protein as described in Example 10, wherein the VH comprises (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 comprises (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. Example 14. The α4β7 binding protein as described in Example 10, wherein the VH comprises (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 comprises (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. Example 15. The α4β7 binding protein as described in Example 10, wherein the VH comprises (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 comprises (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. Example 16. The α4β7 binding protein as described in Example 10, wherein the VH comprises (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 comprises (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. Example 17. The α4β7 binding protein as described in Example 10, wherein the VH comprises (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 comprises (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. Example 18. The α4β7 binding protein as described in Example 10, wherein 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. Example 19. The α4β7 binding protein as described in Example 10, wherein 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. Example 20. The α4β7 binding protein as described in Example 10, wherein 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. Example 21. The α4β7 binding protein as described in Example 10, wherein 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. Example 22. The α4β7 binding protein as described in Example 10, wherein 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. Example 23. The α4β7 binding protein as described in Example 10, wherein 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. Example 24. The α4β7 binding protein as described in Example 10, wherein the VH comprises (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 comprises (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. Example 25. The α4β7 binding protein as described in Example 10, wherein the VH comprises (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 comprises (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. Example 26. The α4β7 binding protein as described in Example 10, wherein the VH comprises (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 comprises (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. Example 27. The α4β7 binding protein as described in Example 10, wherein the VH comprises (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 comprises (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. Example 28. The α4β7 binding protein as described in Example 10, wherein the VH comprises (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 comprises (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. Example 29. The α4β7 binding protein as described in Example 10, wherein the VH comprises (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 comprises (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. Example 30. The α4β7 binding protein as described in Example 10, wherein the VH comprises (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 comprises (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. Example 31. The α4β7 binding protein as described in Example 10, wherein the VH comprises (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 comprises (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. Example 32. The α4β7 binding protein as described in Example 10, wherein the VH comprises (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 comprises (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. Example 33. The α4β7 binding protein as described in Example 10, wherein the VH comprises (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 comprises (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. Example 34. The α4β7 binding protein as described in Example 10, wherein the VH comprises (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 comprises (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. Example 35. The α4β7 binding protein as described in Example 10, wherein the VH comprises (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 comprises (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. Example 36. The α4β7 binding protein as described in Example 10, wherein the VH comprises (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 comprises (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. Example 37. The α4β7 binding protein as described in Example 10, wherein the VH comprises (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 comprises (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. Example 38. The α4β7 binding protein as described in Example 10, wherein the VH comprises (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 comprises (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. Example 39. The α4β7 binding protein as described in Example 10, wherein the VH comprises (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 comprises (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. Example 40. The α4β7 binding protein as described in Example 10, wherein the VH comprises (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 comprises (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. Example 41. The α4β7 binding protein as described in Example 10, wherein the VH comprises (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 comprises (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. Example 42. The α4β7 binding protein as described in Example 10, wherein the VH comprises (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 comprises (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. Example 43. The α4β7 binding protein as described in Example 10, wherein the VH comprises (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 comprises (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. Example 44. The α4β7 binding protein as described in Example 10, wherein the VH comprises (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 comprises (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. Example 45. The α4β7 binding protein as described in Example 10, wherein the VH comprises (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 comprises (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. Example 46. The α4β7 binding protein as described in Example 10, wherein the VH comprises (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 comprises (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. Example 47. The α4β7 binding protein as described in Example 10, wherein the VH comprises (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 comprises (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. Example 48. The α4β7 binding protein as described in Example 10, wherein the VH comprises (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 comprises (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. Example 49. The α4β7 binding protein as described in Example 10, wherein the VH comprises (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 comprises (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. Example 50. The α4β7 binding protein as described in Example 10, wherein the VH comprises (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 comprises (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. Example 51. The α4β7 binding protein as described in Example 10, wherein the VH comprises (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 comprises (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. Example 52. The α4β7 binding protein as described in Example 10, wherein the VH comprises (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 comprises (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. Example 53. The α4β7 binding protein as described in Example 10, wherein the VH comprises (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 comprises (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. Example 54. The α4β7 binding protein as described in Example 10, wherein the VH comprises (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 comprises (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. Example 55. The α4β7 binding protein as described in Example 10, wherein the VH comprises (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 comprises (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. Example 56. The α4β7 binding protein as described in Example 10, wherein the VH comprises (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 comprises (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. Example 57. The α4β7 binding protein as described in Example 10, wherein the VH comprises (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 comprises (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. Example 58. The α4β7 binding protein as described in Example 10, wherein the VH comprises (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 comprises (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. Example 59. The α4β7 binding protein as described in Example 10, wherein the VH comprises (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 comprises (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. Example 60. The α4β7 binding protein as described in Example 10, wherein the VH comprises (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 comprises (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. Example 61. The α4β7 binding protein as described in Example 10, wherein the VH comprises (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 comprises (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. Example 62. The α4β7 binding protein as described in Example 10, wherein the VH comprises (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 comprises (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. Example 63. The α4β7 binding protein as described in Example 10, wherein the VH comprises (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 comprises (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. Example 64. The α4β7 binding protein as described in Example 10, wherein the VH comprises (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 comprises (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. Example 65. The α4β7 binding protein as described in Example 10, wherein the VH comprises (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 comprises (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. The α4β7 binding protein as described in Example 10, wherein the VH comprises (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 comprises (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. Example 66. The α4β7 binding protein as described in Example 10, wherein the VH comprises (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 comprises (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. Example 67. The α4β7 binding protein as described in Example 10, wherein the VH comprises (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 comprises (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. Example 68. The α4β7 binding protein as described in Example 10, wherein the VH comprises (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 comprises (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. Example 69. The α4β7 binding protein as described in Example 10, wherein the VH comprises (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 comprises (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. Example 70. The α4β7 binding protein as described in Example 10, wherein the VH comprises (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 comprises (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. Example 71. The α4β7 binding protein as described in Example 10, wherein the VH comprises (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 comprises (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. Example 72. The α4β7 binding protein as described in Example 10, wherein the VH comprises (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 comprises (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. Example 73. The α4β7 binding protein as described in Example 10, wherein the VH comprises (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 comprises (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. Example 74. The α4β7 binding protein as described in Example 10, wherein the VH comprises (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 comprises (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. Example 75. The α4β7 binding protein as described in Example 10, wherein the VH comprises (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 comprises (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. Example 76. The α4β7 binding protein as described in Example 10, wherein the VH comprises (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 comprises (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. Example 77. The α4β7 binding protein as described in Example 10, wherein the VH comprises (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 comprises (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. Example 78. The α4β7 binding protein as described in Example 10, wherein the VH comprises (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 comprises (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. Example 79. The α4β7 binding protein as described in Example 10, wherein the VH comprises (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 comprises (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. Example 80. The α4β7 binding protein as described in Example 10, wherein the VH comprises (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 comprises (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. Example 81. The α4β7 binding protein as described in Example 10, wherein the VH comprises (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 comprises (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. Example 82. The α4β7 binding protein as described in Example 10, wherein the VH comprises (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 comprises (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. Example 83. The α4β7 binding protein as described in Example 10, wherein the VH comprises (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 comprises (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. Example 84. The α4β7 binding protein as described in Example 10, wherein the VH comprises (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 comprises (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. Example 85. The α4β7 binding protein as described in Example 10, wherein the VH comprises (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 comprises (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. Example 86. The α4β7 binding protein as described in Example 10, wherein the VH comprises (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 comprises (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. Example 87. The α4β7 binding protein as described in Example 10, wherein the VH comprises (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 comprises (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. Example 88. The α4β7 binding protein as described in Example 10, wherein the VH comprises (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 comprises (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. Example 89. The α4β7 binding protein as described in Example 10, wherein the VH comprises (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 comprises (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. Example 90. The α4β7 binding protein as described in Example 10, wherein the VH comprises (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 comprises (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. Example 91. The α4β7 binding protein as described in Example 10, wherein the VH comprises (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 comprises (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. Example 92. The α4β7 binding protein as described in Example 10, wherein the VH comprises (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 comprises (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. Example 93. The α4β7 binding protein as described in Example 10, wherein the VH comprises (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 comprises (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. Example 94. The α4β7 binding protein as described in Example 10, wherein the VH comprises (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 comprises (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. Example 95. The α4β7 binding protein as described in Example 10, wherein the VH comprises (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 comprises (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. Example 96. The α4β7 binding protein as described in Example 10, wherein the VH comprises (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 comprises (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. Example 97. The α4β7 binding protein as described in Example 10, wherein the VH comprises (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 comprises (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. Example 98. The α4β7 binding protein as described in Example 10, wherein the VH comprises (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 comprises (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. Example 99. The α4β7 binding protein as described in Example 10, wherein the VH comprises (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 comprises (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. Example 100. The α4β7 binding protein as described in Example 10, wherein the VH comprises (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 comprises (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. Example 101. The α4β7 binding protein as described in any one of Examples 10-100, wherein the VH comprises a sequence having at least 80% sequence identity with the amino acid sequence of any one of SEQ ID NO: 1915-1934, 1940-1966, 1968-1988, and 1992-2014; and the VL comprises a sequence having at least 80% sequence identity with the amino acid sequence of any one of SEQ ID NO: 2021-2040, 2046-2072, 2074-2094, and 2098-2120. Example 102. The α4β7 binding protein as described in Example 101, wherein the VH comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 127, and the VL comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 134. Example 103. The α4β7 binding protein as described in Example 101, wherein 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. Example 104. The α4β7 binding protein as described in Example 101, wherein 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. Example 105. The α4β7 binding protein as described in Example 101, wherein 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. Example 106. The α4β7 binding protein as described in Example 101, wherein 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. Example 107. The α4β7 binding protein as described in Example 101, wherein 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. Example 108. The α4β7 binding protein as described in Example 101, wherein 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. Example 109. The α4β7 binding protein as described in Example 101, wherein 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. Example 110. The α4β7 binding protein as described in Example 101, wherein 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. Example 111. The α4β7 binding protein as described in Example 101, wherein 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. Example 112. The α4β7 binding protein as described in Example 101, wherein 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. Example 113. The α4β7 binding protein as described in Example 101, wherein 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. Example 114. The α4β7 binding protein as described in Example 101, wherein 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. Example 115. The α4β7 binding protein as described in Example 101, wherein 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. Example 116. The α4β7 binding protein as described in Example 101, wherein 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. Example 117. The α4β7 binding protein as described in Example 101, wherein 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. Example 118. The α4β7 binding protein as described in Example 101, wherein 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. Example 119. The α4β7 binding protein as described in Example 101, wherein 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. Example 120. The α4β7 binding protein as described in Example 101, wherein 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. Example 121. The α4β7 binding protein as described in Example 101, wherein 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. Example 122. The α4β7 binding protein as described in Example 101, wherein 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. Example 123. The α4β7 binding protein as described in Example 101, wherein 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. Example 124. The α4β7 binding protein as described in Example 101, wherein 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. Example 125. The α4β7 binding protein as described in Example 101, wherein 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. Example 126. The α4β7 binding protein as described in Example 101, wherein 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. Example 127. The α4β7 binding protein as described in Example 101, wherein 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. Example 128. The α4β7 binding protein as described in Example 101, wherein 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. Example 129. The α4β7 binding protein as described in Example 101, wherein 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. Example 130. The α4β7 binding protein as described in Example 101, wherein 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. Example 131. The α4β7 binding protein as described in Example 101, wherein 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. Example 132. The α4β7 binding protein as described in Example 101, wherein 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. Example 133. The α4β7 binding protein as described in Example 101, wherein 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. Example 134. The α4β7 binding protein as described in Example 101, wherein 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. Example 135. The α4β7 binding protein as described in Example 101, wherein 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. Example 136. The α4β7 binding protein as described in Example 101, wherein 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. Example 137. The α4β7 binding protein as described in Example 101, wherein 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. Example 138. The α4β7 binding protein as described in Example 101, wherein 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. Example 139. The α4β7 binding protein as described in Example 101, wherein 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. Example 140. The α4β7 binding protein as described in Example 101, wherein 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. Example 141. The α4β7 binding protein as described in Example 101, wherein 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. Example 142. The α4β7 binding protein as described in Example 101, wherein 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. Example 143. The α4β7 binding protein as described in Example 101, wherein 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. Example 144. The α4β7 binding protein as described in Example 101, wherein 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. Example 145. The α4β7 binding protein as described in Example 101, wherein 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. Example 146. The α4β7 binding protein as described in Example 101, wherein 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. Example 147. The α4β7 binding protein as described in Example 101, wherein 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. Example 148. The α4β7 binding protein as described in Example 101, wherein 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. Example 149. The α4β7 binding protein as described in Example 101, wherein 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. Example 150. The α4β7 binding protein as described in Example 101, wherein 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. Example 151. The α4β7 binding protein as described in Example 101, wherein 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. Example 152. The α4β7 binding protein as described in Example 101, wherein 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. Example 153. The α4β7 binding protein as described in Example 101, wherein 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. Example 154. The α4β7 binding protein as described in Example 101, wherein 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. Example 155. The α4β7 binding protein as described in Example 101, wherein 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. Example 156. The α4β7 binding protein as described in Example 101, wherein 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. Example 157. The α4β7 binding protein as described in Example 101, wherein 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. Example 158. The α4β7 binding protein as described in Example 101, wherein 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. Example 159. The α4β7 binding protein as described in Example 101, wherein 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. Example 160. The α4β7 binding protein as described in Example 101, wherein 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. Example 161. The α4β7 binding protein as described in Example 101, wherein 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. Example 162. The α4β7 binding protein as described in Example 101, wherein 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. Example 163. The α4β7 binding protein as described in Example 101, wherein 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. Example 164. The α4β7 binding protein as described in Example 101, wherein 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. Example 165. The α4β7 binding protein as described in Example 101, wherein 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. Example 166. The α4β7 binding protein as described in Example 101, wherein 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. Example 167. The α4β7 binding protein as described in Example 101, wherein 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. Example 168. The α4β7 binding protein as described in Example 101, wherein 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. Example 169. The α4β7 binding protein as described in Example 101, wherein 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. Example 170. The α4β7 binding protein as described in Example 101, wherein 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. Example 171. The α4β7 binding protein as described in Example 101, wherein 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. Example 172. The α4β7 binding protein as described in Example 101, wherein 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. Example 173. The α4β7 binding protein as described in Example 101, wherein 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. Example 174. The α4β7 binding protein as described in Example 101, wherein 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. Example 175. The α4β7 binding protein as described in Example 101, wherein 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. Example 176. The α4β7 binding protein as described in Example 101, wherein 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. Example 177. The α4β7 binding protein as described in Example 101, wherein 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. Example 178. The α4β7 binding protein as described in Example 101, wherein 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. Example 179. The α4β7 binding protein as described in Example 101, wherein 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. Example 180. The α4β7 binding protein as described in Example 101, wherein 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. Example 181. The α4β7 binding protein as described in Example 101, wherein 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. Example 182. The α4β7 binding protein as described in Example 101, wherein 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. Example 183. The α4β7 binding protein as described in Example 101, wherein 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. Example 184. The α4β7 binding protein as described in Example 101, wherein 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. Example 185. The α4β7 binding protein as described in Example 101, wherein 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. Example 186. The α4β7 binding protein as described in Example 101, wherein 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. Example 187. The α4β7 binding protein as described in Example 101, wherein 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. Example 188. The α4β7 binding protein as described in Example 101, wherein 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. Example 189. The α4β7 binding protein as described in Example 101, wherein 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. Example 190. The α4β7 binding protein as described in Example 101, wherein 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. Example 191. The α4β7 binding protein as described in Example 101, wherein the VH comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2013, and the VL comprises a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2119. Example 192. The α4β7 binding protein as described in Example 101, wherein 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. Example 193. An α4β7 binding protein, said α4β7 binding protein comprising: a) A heavy chain variable region (VH) comprising an amino acid sequence according to any one of SEQ ID NO: 1909, 1910, 1935-1939, 1967; and b) A light chain variable region (VL) comprising an amino acid sequence according to any one of SEQ ID NO: 2015, 2016, 2041-2045, 2073. Example 194. The α4β7 binding protein as described in Example 193, wherein the VH comprises the amino acid sequence according to SEQ ID NO: 1909; and the VL comprises the amino acid sequence according to SEQ ID NO: 2015. Example 195. The α4β7 binding protein as described in Example 193, wherein the VH comprises the amino acid sequence according to SEQ ID NO: 1910; and the VL comprises the amino acid sequence according to SEQ ID NO: 2016. Example 196. The α4β7 binding protein as described in Example 193, wherein the VH comprises the amino acid sequence according to SEQ ID NO: 1935; and the VL comprises the amino acid sequence according to SEQ ID NO: 2041. Example 197. The α4β7 binding protein as described in Example 193, wherein the VH comprises the amino acid sequence according to SEQ ID NO: 1936; and the VL comprises the amino acid sequence according to SEQ ID NO: 2042. Example 198. The α4β7 binding protein as described in Example 193, wherein the VH comprises the amino acid sequence according to SEQ ID NO: 1937; and the VL comprises the amino acid sequence according to SEQ ID NO: 2043. Example 199. The α4β7 binding protein as described in Example 193, wherein the VH comprises the amino acid sequence according to SEQ ID NO: 1938; and the VL comprises the amino acid sequence according to SEQ ID NO: 2044. Example 200. The α4β7 binding protein as described in Example 193, wherein the VH comprises the amino acid sequence according to SEQ ID NO: 1939; and the VL comprises the amino acid sequence according to SEQ ID NO: 2045. Example 201. The α4β7 binding protein as described in Example 193, wherein the VH comprises the amino acid sequence according to SEQ ID NO: 1967; and the VL comprises the amino acid sequence according to SEQ ID NO: 2073. Example 202. An α4β7 binding protein, said α4β7 binding protein comprising: c) Heavy chain variable region (VH), the heavy chain variable region comprising (i) CDR1 having an amino acid sequence according to any one of SEQ ID NO: 1-106, (ii) CDR2 having an amino acid sequence according to any one of SEQ ID NO: 107-212, and (iii) CDR3 having an amino acid sequence according to any one of SEQ ID NO: 213-318; d) A light chain variable region (VL) comprising (i) a CDR1 having an amino acid sequence according to any one of SEQ ID NO: 319-424, (ii) a CDR2 having an amino acid sequence according to any one of SEQ ID NO: 425-530, and (iii) a CDR3 having an amino acid sequence according to any one of SEQ ID NO: 531-636; and e) Modified Fc, wherein the modified Fc comprises amino acid modifications M252Y, S254T and T256E (YTE) and / or L234A / G237A (LAGA). Example 203. An α4β7 binding protein, said α4β7 binding protein comprising: a) Heavy chain variable region (VH), the heavy chain variable region comprising (i) CDR1 having an amino acid sequence according to any one of SEQ ID NO: 1-106, (ii) CDR2 having an amino acid sequence according to any one of SEQ ID NO: 107-212, and (iii) CDR3 having an amino acid sequence according to any one of SEQ ID NO: 213-318; b) A light chain variable region (VL) comprising (i) a CDR1 having an amino acid sequence according to any one of SEQ ID NO: 319-424, (ii) a CDR2 having an amino acid sequence according to any one of SEQ ID NO: 425-530, and (iii) a CDR3 having an amino acid sequence according to any one of SEQ ID NO: 531-636; and c) The modified Fc, compared with the α4β7 binding protein without the modified Fc, prolongs the half-life of the α4β7 binding protein. Example 204. An α4β7 binding protein, wherein the α4β7 binding protein specifically binds to the epitope of α4β7 and comprises an Fc domain containing amino acid modifications of M252Y, S254T and T256E (YTE) and / or L234A / G237A (LAGA). Example 205. The α4β7 binding protein as described in any one of Examples 202-204, wherein the Fc is the Fc domain of IgG1, IgG2 or IgG4 immunoglobulin. Example 206. The α4β7 binding protein as described in Example 205, wherein the Fc is an IgG1 immunoglobulin domain. Example 207. The α4β7 binding protein as described in Example 205, wherein the Fc is an IgG2 immunoglobulin domain. Example 208. The α4β7 binding protein as described in Example 205, wherein the Fc is the IgG4 immunoglobulin domain. Example 209. A method for treating inflammatory bowel disease in patients in need, the method comprising administering an effective amount of α4β7 binding protein, as described in any one of Examples 1-208, subcutaneously or intravenously to the patient. Example 210. The method as described in Example 209, wherein the inflammatory bowel disease is Crohn's disease or ulcerative colitis. Example 211. The method as described in Example 210, wherein the inflammatory bowel disease is ulcerative colitis. Example 212. The method as described in Example 210, wherein the inflammatory bowel disease is Crohn's disease. Example 213. The method as described in any one of Examples 209-212, wherein the α4β7 binding protein is administered subcutaneously. Example 214. The method as described in any one of Examples 209-212, wherein the α4β7 binding protein is administered intravenously. Example 215. A method for treating an inflammatory disease in a patient in need, the method comprising administering an effective amount of α4β7 binding protein, as described in any one of Examples 1-208, subcutaneously or intravenously to the patient. Example 216. The method as described in Example 215, wherein the inflammatory disease is psoriasis. Example 217. The method as described in Example 215, wherein the inflammatory disease is psoriatic arthritis. Example 218. The method as described in Example 215, wherein the inflammatory disease is hidradenitis suppurativa. Example 219. The method as described in any one of Examples 215-218, wherein the α4β7 binding protein is administered subcutaneously. Example 220. The method as described in any one of Examples 215-218, wherein the α4β7 binding protein is administered intravenously. Example 221. An isolated nucleic acid encoding the α4β7 binding protein as described in any one of Examples 1-208. Example 222. A recombinant host cell comprising the isolated nucleic acid as described in Example 221. Example

[0302] The present disclosure, which is now generally described, will be more readily understood by referring to the following examples, which are included only for the purpose of illustrating certain aspects and embodiments of the disclosure and are not intended to limit the disclosure. Example 1. Computer simulation of affinity maturation and propensity removal of comparative antibodies against α4β7 integrin

[0303] Residue scanning analysis was performed on the comparative antibody against α4β7 integrin, which was humanized from the parent antibody ACT-1. The three-dimensional structure (PDB code 3V4P) of the complex of ACT-1 and its target antigen (human integrin α4β7 integrin) was loaded into MOE software.

[0304] Prior to analysis, the antibody structure was optimized using MOE's automated structure preparation workflow. Structural issues (such as missing atoms or geometric outliers) were corrected, and any other unnecessary crystallographic molecules were removed to prepare an 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. Restricted 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 examined, and the residues involved were recorded for further analysis.

[0305] All residues in the CDR region were systematically scanned using the MOE residue scanning tool. Each residue was mutated one by one to all 19 native amino acids except cysteine, and the effects on binding affinity, stability, and other protein properties were predicted using scoring functions in the MOE. Based on the results, we identified key residues in the CDR region that could be mutated without negatively impacting the binding affinity, stability, or developability of the comparative antibodies. 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 Δaffinity is a measure of the predicted change in affinity compared to a comparison antibody. The absolute value of the number corresponds to the predicted magnitude of improvement. Improvements in affinity are represented by negative values. The value is a dimensionless prediction. Δstability is a measure of the predicted change in stability compared to a comparison antibody. The absolute value of the number corresponds to the magnitude of the predicted improvement. Improvements in stability are represented by negative values. The value is a dimensionless prediction. Example 2. Rehumanization of comparative antibodies against α4β7 integrin

[0306] Parental mouse anti-human α4β7 ACT-1 mouse antibody (the parental monoclonal antibody of the comparative antibody) was humanized using a complementarity-determining region (CDR) transplantation approach. Parental mouse heavy and light chain sequences were modeled onto the human antibody framework. A set of human heavy and light chains was selected for humanization. The goal was to design these heavy and light chain pairs that improved the biophysical properties of the parental antibody while preserving α4β7 integrin binding. These humanized molecules were designed to improve exploitability characteristics during bioprocess scale-up. Example 3. Determination of antibody affinity for α4β7 integrin

[0307] Binding kinetics and affinity constants were determined at 25°C in HBS-P+ running buffer (containing 1 mM Mn2+, 1 mM Ca2+, and 1 mM Mg2+) using an SPR system equipped with a CM5 chip functionalized with useful anti-human Fc antibodies. After stabilization in the running buffer for a period of time, antibodies previously diluted to 1–1.5 μg / mL were captured on the chip 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 and injected at a flow rate of 30 μL / min for 180 seconds, followed by a dissociation phase using only running buffer at a flow rate of 30 μL / min for 1200 seconds. Samples were injected onto freshly captured mAbs in a multi-cycle manner, and the capture surface was regenerated by injecting 10 mM glycine (pH 1.5). Data were processed and analyzed using SPR analysis software, where sensor maps were fitted to a 1:1 binding model to determine the apparent association (ka) and dissociation rate constant (kd). Their ratio provides the apparent equilibrium dissociation constant or affinity constant (KD = kd / ka). The results are summarized in Table 5. Table 5 Example 4. Binding to α4β7 integrin or α4β1 integrin on cells.

[0308] Binding to antibodies against either α4β7 or α4β1 integrin expressed on the cells was determined using FACS and two cell lines. The first cell line was RPMI-8866, which is known to express only α4β7 integrin. The second cell line was Ramos, which is known to express only α4β1. Briefly, cells were cultured and harvested according to the standard vendor's 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 a 1:1000 dilution of Alexa Fluor 488-conjugated goat anti-human IgG secondary antibody. Cells were incubated at 4°C in the dark for 1 hour. Cells were then washed, and the MFI of cells in each well was recorded by flow cytometry via FACS. Subsequent data were analyzed using a GraphPad Prism. The EC50 value was determined as the antibody concentration required to reach 50% of the maximum platform MFI. Anti-α4β7 integrin comparison antibodies, as well as antibodies 1 and 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 [the table / information]. Figure 1 and Figure 2 middle. Table 6 NB – No binding was observed within the tested concentration range. Example 5. Inhibition of cell adhesion via MAdCAM-1 and α4β7 integrin or VCAM-1 and α4β1 integrin

[0309] Integrins mediate cell adhesion by binding to various cell adhesion molecules. Specifically, α4β7 integrin mediates adhesion by binding to MAdCAM-1, while α4β7 integrin mediates adhesion by binding to VCAM-1. To determine the ability of antibodies to block cell adhesion mediated by 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 α4β7 and α4β1). Briefly, plates were pre-prepared by coating wells with MAdCAM-1 diluted to 0.4 µg / mL in PBS or VCAM-1 diluted to 0.5 µg / mL in PBS. The plates were incubated overnight at 4°C. The next day, cells were harvested according to the standard supplier's instructions. Cells were stained with calcein AM at a ratio of 1 µL of 1 mM calcein AM / 1 mL of 1 × 10⁻⁶ mol / L styraxylene. 6Cells were incubated at 37°C for 30 min. Cells were then washed and resuspended in assay medium consisting of DMEM, 0.1% BSA, 10 mM HEPES, and 0.5 mM MnCl2 to achieve a cell density of 800,000 cells / mL. The purified antibody was mixed with cells at a 1:1 volume ratio, gently centrifuged at 10 x g for 1 min, and incubated at 37°C for 30 min. The antibody was 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. Fluorescence values ​​of individual wells were read using a plate reader with excitation at 485 nm and emission at 520 nm. Wells were then gently washed twice with wash buffer, and the plate was analyzed again in the same manner. Subsequent data were analyzed using a GraphPad Prism. The IC50 value was determined as the antibody concentration required to inhibit 50% of the observed maximum cell adhesion. Comparative studies showed that the antibody and its variants specifically inhibited MAdCAM-1-mediated cell adhesion, but not VCAM-1-mediated cell 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 [the table / information]. Figure 3 and Figure 4 middle. Table 7 NT – Untested. No inhibition was observed in NI – within the tested concentration range. equivalent

[0310] This disclosure may be implemented in other specific forms without departing from its spirit or essential characteristics. Therefore, the foregoing embodiments should be considered illustrative in all respects and not as limiting of the disclosure herein. Consequently, the scope of this disclosure is indicated by the appended claims rather than the foregoing description, and all variations falling within the meaning and scope of equivalents of the claims are intended to be included within said scope.

Claims

1. An α4β7-binding protein, said α4β7-binding protein comprising: (a) a heavy chain variable region (VH) comprising (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; as well as (b) a light chain variable region (VL) comprising (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; (a) a heavy chain variable region (VH) comprising (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; as well as (b) a light chain variable region (VL) comprising (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; (a) a heavy chain variable region (VH) comprising (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; as well as (b) a light chain variable region (VL) comprising (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; (a) a heavy chain variable region (VH) comprising (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; as well as (b) a light chain variable region (VL) comprising (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; (a) a heavy chain variable region (VH) comprising (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; as well as (b) a light chain variable region (VL) comprising (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; (a) a heavy chain variable region (VH) comprising (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; as well as (b) A light chain variable region (VL) comprising (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; (a) a heavy chain variable region (VH) comprising (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; as well as (b) a light chain variable region (VL) comprising (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; (a) a heavy chain variable region (VH) comprising (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; as well as (b) a light chain variable region (VL) comprising (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; (a) a heavy chain variable region (VH) comprising (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; as well as (b) A light chain variable region (VL) comprising (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; (a) a heavy chain variable region (VH) comprising (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; as well as (b) A light chain variable region (VL) comprising (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; (a) a heavy chain variable region (VH) comprising (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; as well as (b) A light chain variable region (VL) comprising (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; (a) a heavy chain variable region (VH) comprising (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; as well as (b) a light chain variable region (VL) comprising (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; (a) a heavy chain variable region (VH) comprising (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; as well as (b) a light chain variable region (VL) comprising (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; (a) a heavy chain variable region (VH) comprising (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; as well as (b) a light chain variable region (VL) comprising (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; (a) a heavy chain variable region (VH) comprising (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; as well as (b) A light chain variable region (VL) comprising (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; (a) a heavy chain variable region (VH) comprising (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; as well as (b) A light chain variable region (VL) comprising (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; (a) a heavy chain variable region (VH) comprising (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; as well as (b) a light chain variable region (VL) comprising (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; (a) a heavy chain variable region (VH) comprising (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; as well as (b) a light chain variable region (VL) comprising (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; (a) a heavy chain variable region (VH) comprising (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; as well as (b) a light chain variable region (VL) comprising (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; (a) a heavy chain variable region (VH) comprising (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; as well as (b) A light chain variable region (VL) comprising (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; (a) a heavy chain variable region (VH) comprising (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; as well as (b) a light chain variable region (VL) comprising (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; (a) a heavy chain variable region (VH) comprising (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; as well as (b) a light chain variable region (VL) comprising (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; (a) a heavy chain variable region (VH) comprising (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; as well as (b) A light chain variable region (VL) comprising (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; (a) a heavy chain variable region (VH) comprising (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; as well as (b) A light chain variable region (VL) comprising (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; (a) a heavy chain variable region (VH) comprising (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; as well as (b) A light chain variable region (VL) comprising (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; (a) a heavy chain variable region (VH) comprising (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; as well as (b) A light chain variable region (VL) comprising (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; (a) a heavy chain variable region (VH) comprising (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; as well as (b) a light chain variable region (VL) comprising (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; (a) a heavy chain variable region (VH) comprising (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; as well as (b) A light chain variable region (VL) comprising (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; (a) a heavy chain variable region (VH) comprising (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; as well as (b) A light chain variable region (VL) comprising (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; (a) a heavy chain variable region (VH) comprising (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; as well as (b) a light chain variable region (VL) comprising (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; (a) a heavy chain variable region (VH) comprising (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; as well as (b) A light chain variable region (VL) comprising (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; (a) a heavy chain variable region (VH) comprising (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; as well as (b) a light chain variable region (VL) comprising (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; (a) a heavy chain variable region (VH) comprising (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; as well as (b) a light chain variable region (VL) comprising (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; (a) a heavy chain variable region (VH) comprising (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; as well as (b) A light chain variable region (VL) comprising (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; (a) a heavy chain variable region (VH) comprising (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; as well as (b) A light chain variable region (VL) comprising (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; (a) a heavy chain variable region (VH) comprising (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; as well as (b) A light chain variable region (VL) comprising (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; (a) a heavy chain variable region (VH) comprising (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; as well as (b) a light chain variable region (VL) comprising (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; (a) a heavy chain variable region (VH) comprising (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; as well as (b) A light chain variable region (VL) comprising (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; (a) a heavy chain variable region (VH) comprising (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; as well as (b) A light chain variable region (VL) comprising (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; (a) a heavy chain variable region (VH) comprising (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; as well as (b) A light chain variable region (VL) comprising (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; (a) a heavy chain variable region (VH) comprising (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; as well as (b) A light chain variable region (VL) comprising (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; (a) a heavy chain variable region (VH) comprising (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; as well as (b) a light chain variable region (VL) comprising (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; (a) a heavy chain variable region (VH) comprising (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; as well as (b) a light chain variable region (VL) comprising (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; (a) a heavy chain variable region (VH) comprising (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; as well as (b) A light chain variable region (VL) comprising (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; (a) a heavy chain variable region (VH) comprising (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; as well as (b) A light chain variable region (VL) comprising (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; (a) a heavy chain variable region (VH) comprising (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; as well as (b) A light chain variable region (VL) comprising (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; (a) a heavy chain variable region (VH) comprising (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; as well as (b) a light chain variable region (VL) comprising (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; (a) a heavy chain variable region (VH) comprising (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; as well as (b) A light chain variable region (VL) comprising (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; (a) a heavy chain variable region (VH) comprising (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; as well as (b) A light chain variable region (VL) comprising (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; (a) a heavy chain variable region (VH) comprising (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; as well as (b) A light chain variable region (VL) comprising (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; (a) a heavy chain variable region (VH) comprising (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; as well as (b) a light chain variable region (VL) comprising (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; (a) a heavy chain variable region (VH) comprising (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; as well as (b) a light chain variable region (VL) comprising (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; (a) a heavy chain variable region (VH) comprising (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; as well as (b) A light chain variable region (VL) comprising (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; (a) a heavy chain variable region (VH) comprising (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; as well as (b) A light chain variable region (VL) comprising (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; (a) a heavy chain variable region (VH) comprising (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; as well as (b) A light chain variable region (VL) comprising (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: 59; (a) a heavy chain variable region (VH) comprising (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; as well as (b) a light chain variable region (VL) comprising (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; (a) a heavy chain variable region (VH) comprising (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; as well as (b) A light chain variable region (VL) comprising (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; (a) a heavy chain variable region (VH) comprising (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; as well as (b) A light chain variable region (VL) comprising (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; (a) a heavy chain variable region (VH) comprising (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; as well as (b) A light chain variable region (VL) comprising (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; (a) a heavy chain variable region (VH) comprising (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; as well as (b) A light chain variable region (VL) comprising (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; (a) a heavy chain variable region (VH) comprising (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; as well as (b) A light chain variable region (VL) comprising (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; (a) a heavy chain variable region (VH) comprising (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; as well as (b) A light chain variable region (VL) comprising (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; (a) a heavy chain variable region (VH) comprising (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; as well as (b) A light chain variable region (VL) comprising (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; (a) a heavy chain variable region (VH) comprising (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; as well as (b) a light chain variable region (VL) comprising (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; (a) a heavy chain variable region (VH) comprising (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; as well as (b) A light chain variable region (VL) comprising (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; (a) a heavy chain variable region (VH) comprising (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; as well as (b) A light chain variable region (VL) comprising (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; (a) a heavy chain variable region (VH) comprising (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; as well as (b) A light chain variable region (VL) comprising (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; (a) a heavy chain variable region (VH) comprising (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; as well as (b) A light chain variable region (VL) comprising (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; (a) a heavy chain variable region (VH) comprising (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; as well as (b) A light chain variable region (VL) comprising (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; (a) a heavy chain variable region (VH) comprising (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; as well as (b) A light chain variable region (VL) comprising (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; (a) a heavy chain variable region (VH) comprising (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; as well as (b) A light chain variable region (VL) comprising (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; (a) a heavy chain variable region (VH) comprising (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; as well as (b) A light chain variable region (VL) comprising (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; (a) a heavy chain variable region (VH) comprising (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; as well as (b) a light chain variable region (VL) comprising (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; (a) a heavy chain variable region (VH) comprising (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; as well as (b) A light chain variable region (VL) comprising (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; (a) a heavy chain variable region (VH) comprising (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; as well as (b) A light chain variable region (VL) comprising (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; (a) a heavy chain variable region (VH) comprising (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; as well as (b) a light chain variable region (VL) comprising (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; (a) a heavy chain variable region (VH) comprising (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; as well as (b) a light chain variable region (VL) comprising (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; (a) a heavy chain variable region (VH) comprising (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; as well as (b) a light chain variable region (VL) comprising (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; (a) a heavy chain variable region (VH) comprising (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; as well as (b) A light chain variable region (VL) comprising (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; (a) a heavy chain variable region (VH) comprising (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; as well as (b) A light chain variable region (VL) comprising (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; (a) a heavy chain variable region (VH) comprising (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; as well as (b) A light chain variable region (VL) comprising (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; (a) a heavy chain variable region (VH) comprising (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; as well as (b) a light chain variable region (VL) comprising (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; (a) a heavy chain variable region (VH) comprising (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; as well as (b) A light chain variable region (VL) comprising (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; (a) a heavy chain variable region (VH) comprising (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; as well as (b) a light chain variable region (VL) comprising (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; (a) a heavy chain variable region (VH) comprising (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; as well as (b) A light chain variable region (VL) comprising (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; (a) a heavy chain variable region (VH) comprising (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; as well as (b) a light chain variable region (VL) comprising (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; (a) a heavy chain variable region (VH) comprising (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; as well as (b) A light chain variable region (VL) comprising (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; (a) a heavy chain variable region (VH) comprising (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; as well as (b) A light chain variable region (VL) comprising (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; (a) a heavy chain variable region (VH) comprising (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; as well as (b) a light chain variable region (VL) comprising (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; (a) a heavy chain variable region (VH) comprising (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; as well as (b) a light chain variable region (VL) comprising (i) a CDR1 having the amino acid sequence according to SEQ ID NO: 423; (ii) a CDR2 having the amino acid sequence according to SEQ ID NO: 529; and (iii) a CDR3 having the amino acid sequence according to SEQ ID NO: 635; or (a) a heavy chain variable region (VH) comprising (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; as well as (b) A light chain variable region (VL) comprising (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.

2. An α4β7-binding protein, said α4β7-binding protein comprising: a) a heavy chain variable region (VH), the heavy chain variable region comprising (i) a CDR1 having an amino acid sequence according to any one of SEQ ID NO: 7-26, 32-58, 60-80, and 84-106; (ii) a CDR2 having an amino acid sequence according to any one of SEQ ID NO: 113-132, 138-164, 166-186, and 190-212; and (iii) a CDR3 having an amino acid sequence according to any one of SEQ ID NO: 219-238, 244-270, 272-292, and 296-318; and b) A light chain variable region (VL) comprising (i) a CDR1 having an amino acid sequence according to any one of SEQ ID NO: 325-344, 350-376, 378-398 and 402-424; (ii) a CDR2 having an amino acid sequence according to any one of SEQ ID NO: 431-450, 456-482, 484-504 and 508-530; and (iii) a CDR3 having an amino acid sequence according to any one of SEQ ID NO: 537-556, 562-588, 590-610 and 614-636.

3. The α4β7 binding protein of claim 1 or claim 2, wherein the VH comprises an amino acid sequence having at least 80% sequence identity with any one of SEQ ID NO: 1915-1934, 1940-1966, 1968-1988, and 1992-2014; and the VL comprises an amino acid sequence having at least 80% sequence identity with any one of SEQ ID NO: 2021-2040, 2046-2072, 2074-2094, and 2098-2120.

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

5. An α4β7-binding protein, said α4β7-binding protein comprising: (a) Heavy chain variable region (VH), the heavy chain variable region 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; as well as (b) a light chain variable region (VL) comprising (i) a CDR1 having the amino acid sequence according to SEQ ID NO: 321, (ii) a CDR2 having the amino acid sequence according to SEQ ID NO: 427, and (iii) a CDR3 having the amino acid sequence according to SEQ ID NO: 533; or (a) Heavy chain variable region (VH), the heavy chain variable region 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; as well as (b) a light chain variable region (VL) comprising (i) a CDR1 having the amino acid sequence according to SEQ ID NO: 322, (ii) a CDR2 having the amino acid sequence according to SEQ ID NO: 428, and (iii) a CDR3 having the amino acid sequence according to SEQ ID NO: 534; or (a) Heavy chain variable region (VH), the heavy chain variable region 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; as well as (b) A light chain variable region (VL) comprising (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 323, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 429, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO: 535; (a) Heavy chain variable region (VH), the heavy chain variable region 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; as well as (b) a light chain variable region (VL) comprising (i) a CDR1 having the amino acid sequence according to SEQ ID NO: 324, (ii) a CDR2 having the amino acid sequence according to SEQ ID NO: 430, and (iii) a CDR3 having the amino acid sequence according to SEQ ID NO: 536; or (a) Heavy chain variable region (VH), the heavy chain variable region 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; as well as (b) a light chain variable region (VL) comprising (i) a CDR1 having the amino acid sequence according to SEQ ID NO: 399, (ii) a CDR2 having the amino acid sequence according to SEQ ID NO: 505, and (iii) a CDR3 having the amino acid sequence according to SEQ ID NO: 611; or (a) Heavy chain variable region (VH), the heavy chain variable region 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; as well as (b) a light chain variable region (VL) comprising (i) a CDR1 having the amino acid sequence according to SEQ ID NO: 400, (ii) a CDR2 having the amino acid sequence according to SEQ ID NO: 506, and (iii) a CDR3 having the amino acid sequence according to SEQ ID NO: 612; or (a) Heavy chain variable region (VH), the heavy chain variable region 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; as well as (b) A light chain variable region (VL) comprising (i) a CDR1 having an amino acid sequence according to SEQ ID NO: 401, (ii) a CDR2 having an amino acid sequence according to SEQ ID NO: 507, and (iii) a CDR3 having an amino acid sequence according to SEQ ID NO:

613.

6. The α4β7 binding protein of claim 5, wherein the VH comprises a sequence having at least 80% sequence identity with any one of the amino acid sequences of SEQ ID NO: 1911-1914 and 1925-1927; and the VL comprises a sequence having at least 80% sequence identity with any one of the amino acid sequences of SEQ ID NO: 2017-2020 and 2031-2033.

7. The α4β7 binding protein of claim 5 or claim 6, wherein the VH comprises A sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1911, and the VL comprising 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 contains a sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1925, and the VL contains 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.

8. An α4β7-binding protein, said α4β7-binding protein comprising: a) A heavy chain variable region (VH) comprising an amino acid sequence according to any one of SEQ ID NO: 1909, 1910, 1935-1939, 1967; and b) A light chain variable region (VL) comprising an amino acid sequence according to any one of SEQ ID NO: 2015, 2016, 2041-2045, 2073.

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

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

11. An α4β7-binding protein, said α4β7-binding protein comprising: c) Heavy chain variable region (VH), the heavy chain variable region comprising (i) CDR1 having an amino acid sequence according to any one of SEQ ID NO: 1-106, (ii) CDR2 having an amino acid sequence according to any one of SEQ ID NO: 107-212, and (iii) CDR3 having an amino acid sequence according to any one of SEQ ID NO: 213-318; d) A light chain variable region (VL) comprising (i) a CDR1 having an amino acid sequence according to any one of SEQ ID NO: 319-424, (ii) a CDR2 having an amino acid sequence according to any one of SEQ ID NO: 425-530, and (iii) a CDR3 having an amino acid sequence according to any one of SEQ ID NO: 531-636; and e) The modified Fc, compared with the α4β7 binding protein without the modified Fc, prolongs the half-life of the α4β7 binding protein.

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

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

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

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

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

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

18. The method of any one of claims 15-17, wherein the α4β7 binding protein is administered subcutaneously.

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

20. An isolated nucleic acid encoding the α4β7 binding protein as described in any one of claims 1-14.

21. A recombinant host cell comprising the isolated nucleic acid as described in claim 20.

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

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