Integrin alpha7beta1 antibodies and uses thereof

Abstract

The present disclosure provides, inter alia, antibodies or antigen-binding fragments that bind to the calf-1 domain or the calf-2 domain of a7b1 integrin. Anti-a7b1 antibodies of the present disclosure effectively stabilize a7b1 integrin in the extended-closed and extended-open conformations, which enhances binding to laminin.

Description

Cross-reference to related applications

[0001] This application claims the benefit of priority to U.S. Provisional Application No. 63 / 667,476, filed July 3, 2024, and U.S. Provisional Application No. 63 / 566,145, filed March 15, 2024, the contents of which are incorporated herein by reference in their entirety. Background Technology

[0002] Integrin α7β1 is the major laminin receptor in skeletal and cardiac muscle. It acts as a transmembrane link between the basal layer and muscle cell membranes to maintain the functional integrity of muscle cells. Loss of function due to mutations in ITGA7 in humans leads to congenital myopathy and adult-onset cardiomyopathy. Conversely, overexpression of ITGA7 in skeletal muscle improves the development of muscular dystrophy, and overexpression of ITGA7 in cardiomyocytes protects cardiomyocytes from ischemia / reperfusion injury.

[0003] Muscular dystrophy (such as Duchenne muscular dystrophy (DMD)) is a group of inherited degenerative disorders characterized by progressive degeneration of muscles throughout the body and loss of muscle-related function. Existing treatments for muscular dystrophy disorders (including dystrophinosis) focus only on mitigating the effects of the disease and improving quality of life, typically through glucocorticoids, physical therapy, or the use of orthopedic devices. New approaches to treating dystrophinosis (including DMD) are needed. Summary of the Invention

[0004] This disclosure specifically provides the therapeutic use of integrin α7β1 antibodies and such antibodies in the effective treatment of diseases or disorders associated with muscle membrane integrity, such as Duchenne muscular dystrophy (DMD). As described herein, this disclosure is partly based on the identification of integrin α7β1 antibodies that effectively stabilize α7β1 integrin in both extended-closed and extended-open conformations and thus enhance binding to laminin ligands. Therefore, the anti-α7β1 antibodies of this disclosure effectively increase the adhesion of the muscle membrane (myofibroblast membrane) to the extracellular matrix, restore some or all of the muscle damage caused by the lack of functional dystrophin, and ultimately improve motor function, increase muscle strength, and reduce fibrosis in patients with dystrophin-resistant muscle disease.

[0005] In one aspect, this disclosure provides an antibody or antigen-binding fragment thereof that binds to the calf-2 domain of the α7β1 integrin but does not compete with a 20TFT antibody, wherein the antibody stabilizes the extended conformation of the α7β1 integrin.

[0006] In one aspect, this disclosure provides an antibody or antigen-binding fragment thereof that binds to α7β1 integrin and competes with a reference antibody for binding to α7β1, wherein the reference antibody comprises HCDR1 of sequence GFTFSSYT (SEQ ID NO: 2, HCDR1B), HCDR2 of sequence ISIVGNYI (SEQ ID NO: 16, HCDR2B), HCDR3 of sequence ARRKWEHDAFDI (SEQ ID NO: 32, HCDR3B), LCDR1 of sequence SLRSYY (SEQ ID NO: 47, LCDR1B), LCDR2 of sequence GKN (SEQ ID NO: 59, LCDR2B), and LCDR3 of sequence TSRDNSGNHVV (SEQ ID NO: 70, LCDR3B).

[0007] In one aspect, this disclosure provides an antibody or antigen-binding fragment thereof that binds to an α7β1 integrin, wherein the antibody or antigen-binding fragment comprises (a) a functional unit for stabilizing the extended conformation of the α7β1 integrin, and optionally (b) an Fc domain. In some embodiments, the antibody is not a 20TFT antibody.

[0008] In one aspect, the present disclosure provides an antibody or antigen-binding fragment thereof that binds to α7β1, wherein the antibody or antigen-binding fragment thereof binds to a region comprising the amino acid sequence of integrin α7 at positions 856-862, 867-889, 1011-1017, 897-905 or 1002-1010, and wherein the antibody or antigen-binding fragment thereof stabilizes the extended conformation of α7β1 integrin.

[0009] In some embodiments, the antibody or its antigen-binding fragment binds to the region containing amino acid positions 856-862, 867-889, or 1011-1017 of the integrin α7. In some embodiments, the antibody or its antigen-binding fragment binds to the region containing amino acid positions 856-862 of the integrin α7. In some embodiments, the antibody or its antigen-binding fragment binds to the region containing amino acid positions 867-889 of the integrin α7. In some embodiments, the antibody or its antigen-binding fragment binds to the region containing amino acid positions 1011-1017 of the integrin α7.

[0010] In some embodiments, the antibody or its antigen-binding fragment binds to a region containing residues M856, A857, I858, P859, Q860, Q861, and L862 of integrin α7. In some embodiments, the antibody or its antigen-binding fragment binds to a region containing residues V867, V868, R869, G870, E871, R872, A873, M874, Q875, S876, E877, R878, D879, V880, G881, S882, K883, V884, K885, Y886, E887, V888, and T889 of integrin α7. In some embodiments, the antibody or its antigen-binding fragment binds to a region containing residues F1011, D1102, R1103, A1104, A1105, V1106, and L1107 of integrin α7.

[0011] In some embodiments, the antibody or its antigen-binding fragment binds to the region containing amino acid positions 897-905 or 1002-1010 of the integrin α7. In some embodiments, the antibody or its antigen-binding fragment binds to the region containing amino acid positions 897-905 of the integrin α7. In some embodiments, the antibody or its antigen-binding fragment binds to the region containing amino acid positions 1002-1010 of the integrin α7.

[0012] In some embodiments, the antibody or its antigen-binding fragment binds to regions containing integrin α7 at positions L897, R898, T899, L900, G901, S902, A903, F904, and L905. In some embodiments, the antibody or its antigen-binding fragment binds to regions containing integrin α7 at positions V1002, V1003, F1004, S1005, C1006, P1007, L1008, Y1009, and S1100.

[0013] In one aspect, this disclosure provides an antibody or antigen-binding fragment thereof that binds to the calf-1 domain of the α7β1 integrin and stabilizes the extended conformation of the α7β1 integrin.

[0014] In one aspect, this disclosure provides an antibody or antigen-binding fragment that binds to the α7β1 integrin and competes with a reference antibody for binding to the α7β1 antibody, wherein the reference antibody comprises HCDR1 of the sequence GYSFTRYW (SEQ ID NO: 7, HCDR1G), HCDR2 of the sequence IDPSDSET (SEQ ID NO: 22, HCDR2H), HCDR3 of the sequence ARGGYFGEGWYFDV (SEQ ID NO: 38, HCDR3H), LCDR1 of the sequence QSLVHRNGNTY (SEQ ID NO: 51, LCDR1F), LCDR2 of the sequence KVS (SEQ ID NO: 63, LCDR2F), and LCDR3 of the sequence SQSTHVPWT (SEQ ID NO: 75, LCDR3G).

[0015] In one aspect, this disclosure provides an antibody or antigen-binding fragment that binds to the α7β1 integrin and competes with a reference antibody for binding to the α7β1 antibody, wherein the reference antibody comprises HCDR1 of the sequence GFSLTSYG (SEQ ID NO: 9, HCDR1I), HCDR2 of the sequence IWVGGIT (SEQ ID NO: 24, HCDR2J), HCDR3 of the sequence ARDGYYGDFDV (SEQ ID NO: 40, HCDR3J), LCDR1 of the sequence QDINKF (SEQ ID NO: 53, LCDR1H), LCDR2 of the sequence YTS (SEQ ID NO: 65, LCDR2H), and LCDR3 of the sequence LQYDNLRT (SEQ ID NO: 77, LCDR3I).

[0016] In one aspect, this disclosure provides an antibody or antigen-binding fragment that binds to the α7β1 integrin, the antibody or antigen-binding fragment comprising (a) a functional unit for binding to the calf-1 domain of the α7β1 integrin and (b) an Fc domain.

[0017] In one aspect, this disclosure provides an antibody or antigen-binding fragment that binds to the α7β1 integrin, wherein the antibody binds to a region comprising positions 771-778, 793-779, or 803-805 of the α7 integrin, wherein the antibody stabilizes the extended conformation of the α7β1 integrin. In some embodiments, the region comprises amino acids R771, A772, L773, D774, A776, E777, K778, E793, N796, K799, Q803, and / or T805 according to human α7 amino acid numbers.

[0018] In one aspect, this disclosure provides an antibody or antigen-binding fragment that binds to α7β1 integrin, wherein the reference antibody comprises HCDR1 of the sequence GFTFSSYT (SEQ ID NO: 2, HCDR1B), HCDR2 of the sequence ISIVGNYI (SEQ ID NO: 16, HCDR2B), HCDR3 of the sequence ARRKWEHDAFDI (SEQ ID NO: 32, HCDR3B), LCDR1 of the sequence SLRSYY (SEQ ID NO: 47, LCDR1B), LCDR2 of the sequence GKN (SEQ ID NO: 59, LCDR2B), and LCDR3 of the sequence TSRDNSGNHVV (SEQ ID NO: 70, LCDR3B).

[0019] In one aspect, this disclosure provides an antibody or antigen-binding fragment that binds to α7β1 integrin, wherein the reference antibody comprises HCDR1 of the sequence GYTFTGYY (SEQ ID NO: 1, HCDR1A), HCDR2 of the sequence INPNSGGT (SEQ ID NO: 15, HCDR2A), HCDR3 of the sequence AREGANWDYYYYGMDV (SEQ ID NO: 31, HCDR3A), LCDR1 of the sequence SSNIGSKT (SEQ ID NO: 46, LCDR1A), LCDR2 of the sequence SNN (SEQ ID NO: 58, LCDR2A), and LCDR3 of the sequence AAWDDSLNGPV (SEQ ID NO: 69, LCDR3A).

[0020] In one aspect, this disclosure provides an antibody or antigen-binding fragment that binds to α7β1 integrin, wherein the reference antibody comprises HCDR1 of the sequence GFTFSSYS (SEQ ID NO: 3, HCDR1C), HCDR2 of the sequence ISTSSSYI (SEQ ID NO: 17, HCDR2C), HCDR3 of the sequence ARRAWESDAFAI (SEQ ID NO: 33, HCDR3C), LCDR1 of the sequence SLRSYY (SEQ ID NO: 47, LCDR1B), LCDR2 of the sequence GKN (SEQ ID NO: 59, LCDR2B), and LCDR3 of the sequence NSRDSSGNHVV (SEQ ID NO: 71, LCDR3C).

[0021] In one aspect, this disclosure provides an antibody or antigen-binding fragment that binds to α7β1 integrin, wherein the reference antibody comprises HCDR1 of the sequence GFTFSSYA (SEQ ID NO: 4, HCDR1D), HCDR2 of the sequence IDSSGGIA (SEQ ID NO: 18, HCDR2D), HCDR3 of the sequence VRDGY (SEQ ID NO: 34, HCDR3D), LCDR1 of the sequence QSLLDSDDGYTY (SEQ ID NO: 48, LCDR1C), LCDR2 of the sequence TLS (SEQ ID NO: 60, LCDR2C), and LCDR3 of the sequence MQRIEFPLT (SEQ ID NO: 72, LCDR3D).

[0022] In one aspect, this disclosure provides an antibody or antigen-binding fragment that binds to α7β1 integrin, wherein the reference antibody comprises HCDR1 of sequence GFTFSSYA (SEQ ID NO: 4, HCDR1D), HCDR2 of sequence IHYSGGTT (SEQ ID NO: 19, HCDR2E), HCDR3 of sequence VKDGY (SEQ ID NO: 35, HCDR3E), LCDR1 of sequence QSLLDSDDGYTY (SEQ ID NO: 48, LCDR1C), LCDR2 of sequence TLS (SEQ ID NO: 60, LCDR2C), and LCDR3 of sequence MQRIEFPLT (SEQ ID NO: 72, LCDR3D).

[0023] In one aspect, this disclosure provides an antibody or antigen-binding fragment that binds to α7β1 integrin, wherein the reference antibody comprises HCDR1 of the sequence GFTFSRFW (SEQ ID NO: 5, HCDR1E), HCDR2 of the sequence TKQDGSEK (SEQ ID NO: 20, HCDR2F), HCDR3 of the sequence AREGSGAYWAFDI (SEQ ID NO: 36, HCDR3F), LCDR1 of the sequence QSLVHNDGNTY (SEQ ID NO: 49, LCDR1D), LCDR2 of the sequence KIS (SEQ ID NO: 49, LCDR1D), and LCDR3 of the sequence LQATQFPLT (SEQ ID NO: 73, LCDR3E).

[0024] In one aspect, this disclosure provides an antibody or antigen-binding fragment that binds to α7β1 integrin, wherein the reference antibody comprises HCDR1 of sequence GGSISSYY (SEQ ID NO: 6, HCDR1F), HCDR2 of sequence IYTRGST (SEQ ID NO: 21, HCDR2G), HCDR3 of sequence ARVFGGNYRFDAFHI (SEQ ID NO: 37, HCDR3G), LCDR1 of sequence SSNIGAGYD (SEQ ID NO: 50, LCDR1E), LCDR2 of sequence GNN (SEQ ID NO: 62, LCDR2E), and LCDR3 of sequence QSYDSSLSGYV (SEQ ID NO: 74, LCDR3F).

[0025] In one aspect, this disclosure provides an antibody or antigen-binding fragment that binds to α7β1 integrin, wherein the reference antibody comprises HCDR1 of sequence GYSFTRYW (SEQ ID NO: 7, HCDR1G), HCDR2 of sequence IDPSDSET (SEQ ID NO: 22, HCDR2H), HCDR3 of sequence ARGGYFGEGWYFDV (SEQ ID NO: 38, HCDR3H), LCDR1 of sequence QSLVHRNGNTY (SEQ ID NO: 51, LCDR1F), LCDR2 of sequence KVS (SEQ ID NO: 63, LCDR2F), and LCDR3 of sequence SQSTHVPWT (SEQ ID NO: 75, LCDR3G).

[0026] In one aspect, this disclosure provides an antibody or antigen-binding fragment that binds to α7β1 integrin, wherein the reference antibody comprises HCDR1 of the sequence GYTFTSYW (SEQ ID NO: 8, HCDR1H), HCDR2 of the sequence IYPSDSYT (SEQ ID NO: 23, HCDR2I), HCDR3 of the sequence TRRANYVGAMDY (SEQ ID NO: 39, HCDR3I), LCDR1 of the sequence SVSSY (SEQ ID NO: 52, LCDR1G), LCDR2 of the sequence ATS (SEQ ID NO: 64, LCDR2G), and LCDR3 of the sequence QQWSSNPLT (SEQ ID NO: 76, LCDR3H).

[0027] In one aspect, this disclosure provides an antibody or antigen-binding fragment that binds to α7β1 integrin, wherein the reference antibody comprises HCDR1 of the sequence GFSLTSYG (SEQ ID NO: 9, HCDR1I), HCDR2 of the sequence IWVGGIT (SEQ ID NO: 24, HCDR2J), HCDR3 of the sequence ARDGYYGDFDV (SEQ ID NO: 40, HCDR3J), LCDR1 of the sequence QDINKF (SEQ ID NO: 53, LCDR1H), LCDR2 of the sequence YTS (SEQ ID NO: 65, LCDR2H), and LCDR3 of the sequence LQYDNLRT (SEQ ID NO: 77, LCDR3I).

[0028] In one aspect, this disclosure provides an antibody or antigen-binding fragment that binds to α7β1 integrin, wherein the reference antibody comprises HCDR1 of the sequence GFSLTSYG (SEQ ID NO: 9, HCDR1I), HCDR2 of the sequence IWAGGIT (SEQ ID NO: 25, HCDR2K), HCDR3 of the sequence ARDGYYGDFDV (SEQ ID NO: 40, HCDR3J), LCDR1 of the sequence QDINKY (SEQ ID NO: 54, LCDR1I), LCDR2 of the sequence YTS (SEQ ID NO: 65, LCDR2H), and LCDR3 of the sequence LQYDNLRT (SEQ ID NO: 77, LCDR3I).

[0029] In one aspect, this disclosure provides an antibody or antigen-binding fragment that binds to α7β1 integrin, wherein the reference antibody comprises HCDR1 of the sequence GFSLTSYG (SEQ ID NO: 9, HCDR1I), HCDR2 of the sequence IWAGGIT (SEQ ID NO: 25, HCDR2K), HCDR3 of the sequence ARDGYYGHFDV (SEQ ID NO: 41, HCDR3K), LCDR1 of the sequence QDINKY (SEQ ID NO: 54, LCDR1I), LCDR2 of the sequence YTS (SEQ ID NO: 65, LCDR2H), and LCDR3 of the sequence LQYDNLRA (SEQ ID NO: 78, LCDR3J).

[0030] In one aspect, this disclosure provides an antibody or antigen-binding fragment that binds to α7β1 integrin, wherein the reference antibody comprises HCDR1 of the sequence GFTFSSDA (SEQ ID NO: 10, HCDR1J), HCDR2 of the sequence ISIGGSA (SEQ ID NO: 26, HCDR2L), HCDR3 of the sequence ARGGDYDAMDY (SEQ ID NO: 42, HCDR3L), LCDR1 of the sequence QSISDL (SEQ ID NO: 55, LCDR1J), LCDR2 of the sequence YAS (SEQ ID NO: 66, LCDR2I), and LCDR3 of the sequence QNGHNFPFT (SEQ ID NO: 79, LCDR3K).

[0031] In one aspect, this disclosure provides an antibody or antigen-binding fragment that binds to α7β1 integrin, wherein the reference antibody comprises HCDR1 of the sequence GFTFSSSA (SEQ ID NO: 11, HCDR1K), HCDR2 of the sequence ISVGGST (SEQ ID NO: 27, HCDR2M), HCDR3 of the sequence ARGGDYDAMDY (SEQ ID NO: 42, HCDR3L), LCDR1 of the sequence QSISDY (SEQ ID NO: 56, LCDR1K), LCDR2 of the sequence YAS (SEQ ID NO: 66, LCDR2I), and LCDR3 of the sequence QNGHSFPFT (SEQ ID NO: 80, LCDR3L).

[0032] In one aspect, this disclosure provides an antibody or antigen-binding fragment that binds to α7β1 integrin, wherein the reference antibody comprises HCDR1 of the sequence GFTFSSSA (SEQ ID NO: 11, HCDR1K), HCDR2 of the sequence ISVGGST (SEQ ID NO: 27, HCDR2M), HCDR3 of the sequence ARGGDYDAMDY (SEQ ID NO: 42, HCDR3L), LCDR1 of the sequence QSISDY (SEQ ID NO: 56, LCDR1K), LCDR2 of the sequence YSS (SEQ ID NO: 67, LCDR2J), and LCDR3 of the sequence QNGHSFPFT (SEQ ID NO: 80, LCDR3L).

[0033] In one aspect, this disclosure provides an antibody or antigen-binding fragment that binds to α7β1 integrin, wherein the reference antibody comprises HCDR1 of the sequence GFTFSSSA (SEQ ID NO: 11, HCDR1K), HCDR2 of the sequence ISVGGST (SEQ ID NO: 27, HCDR2M), HCDR3 of the sequence ARGGDYDPMDY (SEQ ID NO: 43, HCDR3M), LCDR1 of the sequence QSISDY (SEQ ID NO: 56, LCDR1K), LCDR2 of the sequence YAS (SEQ ID NO: 66, LCDR2I), and LCDR3 of the sequence QNGHSFPFT (SEQ ID NO: 80, LCDR3L).

[0034] In one aspect, this disclosure provides an antibody or antigen-binding fragment that binds to α7β1 integrin, wherein the reference antibody comprises HCDR1 of the sequence GFTFSSDA (SEQ ID NO: 10, HCDR1J), HCDR2 of the sequence ISIGGST (SEQ ID NO: 28, HCDR2N), HCDR3 of the sequence ARGGDYDAMDY (SEQ ID NO: 42, HCDR3L), LCDR1 of the sequence QSISDL (SEQ ID NO: 55, LCDR1J), LCDR2 of the sequence YAS (SEQ ID NO: 66, LCDR2I), and LCDR3 of the sequence QNGHNFPFT (SEQ ID NO: 79, LCDR3K).

[0035] In one aspect, this disclosure provides an antibody or antigen-binding fragment that binds to α7β1 integrin, wherein the reference antibody comprises HCDR1 of the sequence GFTFSSSA (SEQ ID NO: 11, HCDR1K), HCDR2 of the sequence ISVGGSI (SEQ ID NO: 29, HCDR2O), HCDR3 of the sequence ARGGDYDAMDY (SEQ ID NO: 42, HCDR3L), LCDR1 of the sequence QSISDY (SEQ ID NO: 56, LCDR1K), LCDR2 of the sequence YAS (SEQ ID NO: 66, LCDR2I), and LCDR3 of the sequence QNGHSFPFT (SEQ ID NO: 80, LCDR3L).

[0036] In one aspect, this disclosure provides an antibody or antigen-binding fragment that binds to α7β1 integrin, wherein the reference antibody comprises HCDR1 of the sequence GFTFSSDA (SEQ ID NO: 10, HCDR1J), HCDR2 of the sequence ISIGGST (SEQ ID NO: 28, HCDR2N), HCDR3 of the sequence ARGGDYDAMDY (SEQ ID NO: 42, HCDR3L), LCDR1 of the sequence QSISDL (SEQ ID NO: 55, LCDR1J), LCDR2 of the sequence YAS (SEQ ID NO: 66, LCDR2I), and LCDR3 of the sequence QNGHNFPFT (SEQ ID NO: 79, LCDR3K).

[0037] In one aspect, this disclosure provides an antibody or antigen-binding fragment that binds to α7β1 integrin, wherein the reference antibody comprises HCDR1 of the sequence GFTFSNCA (SEQ ID NO: 12, HCDR1L), HCDR2 of the sequence ISIGGST (SEQ ID NO: 28, HCDR2N), HCDR3 of the sequence ARGGDYDAMDY (SEQ ID NO: 42, HCDR3L), LCDR1 of the sequence QSISDL (SEQ ID NO: 55, LCDR1J), LCDR2 of the sequence YAS (SEQ ID NO: 66, LCDR2I), and LCDR3 of the sequence QNGHSFPFT (SEQ ID NO: 80, LCDR3L).

[0038] In one aspect, this disclosure provides an antibody or antigen-binding fragment that binds to α7β1 integrin, wherein the reference antibody comprises HCDR1 of the sequence GFTFSSDA (SEQ ID NO: 10, HCDR1J), HCDR2 of the sequence ISIGGST (SEQ ID NO: 28, HCDR2N), HCDR3 of the sequence TRGGDYDAMDY (SEQ ID NO: 44, HCDR3N), LCDR1 of the sequence QSISDL (SEQ ID NO: 55, LCDR1J), LCDR2 of the sequence YAS (SEQ ID NO: 66, LCDR2I), and LCDR3 of the sequence QNGHNFPFT (SEQ ID NO: 79, LCDR3K).

[0039] In one aspect, this disclosure provides an antibody or antigen-binding fragment that binds to α7β1 integrin, wherein the reference antibody comprises HCDR1 of the sequence GFSLSTSDMG (SEQ ID NO: 13, HCDR1M), HCDR2 of the sequence IYWDDDK (SEQ ID NO: 30, HCDR2P), HCDR3 of the sequence VRGTAVVAFYWYFDV (SEQ ID NO: 45, HCDR3O), LCDR1 of the sequence QDINNY (SEQ ID NO: 57, LCDR1L), LCDR2 of the sequence RAN (SEQ ID NO: 68, LCDR2K), and LCDR3 of the sequence LHYDDFPLT (SEQ ID NO: 81, LCDR3M).

[0040] In one aspect, this disclosure provides an antibody or antigen-binding fragment that binds to α7β1 integrin, wherein the reference antibody comprises HCDR1 of the sequence GFSLSTSDLG (SEQ ID NO: 14, HCDR1N), HCDR2 of the sequence IYWDDDK (SEQ ID NO: 30, HCDR2P), HCDR3 of the sequence VRGTAVVAFYWYFDV (SEQ ID NO: 45, HCDR3O), LCDR1 of the sequence QDINNY (SEQ ID NO: 57, LCDR1L), LCDR2 of the sequence RAN (SEQ ID NO: 68, LCDR2K), and LCDR3 of the sequence LQYDDFPLT (SEQ ID NO: 82, LCDR3N).

[0041] In one aspect, this disclosure provides an antibody or antigen-binding fragment that binds to α7β1 integrin, wherein the antibody comprises HCDR1 of sequence GYSFTRYW (SEQ ID NO: 101), HCDR2 of sequence IDPSDSET (SEQ ID NO: 27), and HCDR3 of sequence ARGGYFGEGWYFDV (SEQ ID NO: 38); and LCDR1 of sequence QSLVHRNGNTY (SEQ ID NO: 105), LCDR2 of sequence KVS (SEQ ID NO: 63), and LCDR3 of sequence SQSTHVPWT (SEQ ID NO: 75).

[0042] In one aspect, this disclosure provides an antibody or antigen-binding fragment that binds to α7β1 integrin, wherein the antibody comprises HCDR1 of sequence GYSFTRYW (SEQ ID NO: 101), HCDR2 of sequence IDPSDSET (SEQ ID NO: 102), and HCDR3 of sequence ARGGYFGREWYYDV (SEQ ID NO: 103); and LCDR1 of sequence QSLVHRNGNTY (SEQ ID NO: 105), LCDR2 of sequence EVS (SEQ ID NO: 106), and LCDR3 of sequence SQSTHVPWT (SEQ ID NO: 75).

[0043] In one aspect, this disclosure provides an antibody or antigen-binding fragment that binds to α7β1 integrin, wherein the antibody comprises HCDR1 of sequence GYSFTRYW (SEQ ID NO: 101), HCDR2 of sequence IDPSDSET (SEQ ID NO: 102), and HCDR3 of sequence ARGGYFGEEWYHDV (SEQ ID NO: 104); and LCDR1 of sequence QSLVHRNGNTY (SEQ ID NO: 105), LCDR2 of sequence EVS (SEQ ID NO: 106), and LCDR3 of sequence AQSTQLPYT (SEQ ID NO: 107).

[0044] In one aspect, this disclosure provides an antibody or antigen-binding fragment that binds to α7β1 integrin, wherein the antibody comprises HCDR1 of SEQ ID NO: 101, HCDR2 of SEQ ID NO: 102, HCDR3 of SEQ ID NO: 188, LCDR1 of SEQ ID NO: 105, LCDR2 of SEQ ID NO: 106, and LCDR3 of SEQ ID NO: 198.

[0045] In one aspect, this disclosure provides an antibody or antigen-binding fragment that binds to α7β1 integrin, wherein the antibody comprises HCDR1 of SEQ ID NO: 101, HCDR2 of SEQ ID NO: 102, HCDR3 of SEQ ID NO: 189, LCDR1 of SEQ ID NO: 105, LCDR2 of SEQ ID NO: 106, and LCDR3 of SEQ ID NO: 75.

[0046] In one aspect, this disclosure provides an antibody or antigen-binding fragment that binds to α7β1 integrin, wherein the antibody comprises HCDR1 of SEQ ID NO: 101, HCDR2 of SEQ ID NO: 102, HCDR3 of SEQ ID NO: 190, LCDR1 of SEQ ID NO: 105, LCDR2 of SEQ ID NO: 106, and LCDR3 of SEQ ID NO: 75.

[0047] In one aspect, this disclosure provides an antibody or antigen-binding fragment that binds to α7β1 integrin, wherein the antibody comprises HCDR1 of SEQ ID NO: 101, HCDR2 of SEQ ID NO: 102, HCDR3 of SEQ ID NO: 191, LCDR1 of SEQ ID NO: 105, LCDR2 of SEQ ID NO: 106, and LCDR3 of SEQ ID NO: 75.

[0048] In one aspect, this disclosure provides an antibody or antigen-binding fragment that binds to α7β1 integrin, wherein the antibody comprises HCDR1 of SEQ ID NO: 101, HCDR2 of SEQ ID NO: 102, HCDR3 of SEQ ID NO: 192, LCDR1 of SEQ ID NO: 105, LCDR2 of SEQ ID NO: 106, and LCDR3 of SEQ ID NO: 75.

[0049] In one aspect, this disclosure provides an antibody or antigen-binding fragment that binds to α7β1 integrin, wherein the antibody comprises HCDR1 of SEQ ID NO: 101, HCDR2 of SEQ ID NO: 102, HCDR3 of SEQ ID NO: 193, LCDR1 of SEQ ID NO: 105, LCDR2 of SEQ ID NO: 106, and LCDR3 of SEQ ID NO: 198.

[0050] In one aspect, this disclosure provides an antibody or antigen-binding fragment that binds to α7β1 integrin, wherein the antibody comprises HCDR1 of SEQ ID NO: 101, HCDR2 of SEQ ID NO: 102, HCDR3 of SEQ ID NO: 194, LCDR1 of SEQ ID NO: 105, LCDR2 of SEQ ID NO: 106, and LCDR3 of SEQ ID NO: 107.

[0051] In one aspect, this disclosure provides an antibody or antigen-binding fragment that binds to α7β1 integrin, wherein the antibody comprises HCDR1 of SEQ ID NO: 101, HCDR2 of SEQ ID NO: 102, HCDR3 of SEQ ID NO: 194, LCDR1 of SEQ ID NO: 105, LCDR2 of SEQ ID NO: 196, and LCDR3 of SEQ ID NO: 107.

[0052] In one aspect, this disclosure provides an antibody or antigen-binding fragment that binds to α7β1 integrin, wherein the antibody comprises HCDR1 of SEQ ID NO: 101, HCDR2 of SEQ ID NO: 102, HCDR3 of SEQ ID NO: 195, LCDR1 of SEQ ID NO: 105, LCDR2 of SEQ ID NO: 63, and LCDR3 of SEQ ID NO: 75.

[0053] In one aspect, this disclosure provides an antibody or antigen-binding fragment that binds to α7β1 integrin, wherein the antibody comprises HCDR1 of SEQ ID NO: 101, HCDR2 of SEQ ID NO: 102, HCDR3 of SEQ ID NO: 104, LCDR1 of SEQ ID NO: 105, LCDR2 of SEQ ID NO: 63, and LCDR3 of SEQ ID NO: 75.

[0054] In one aspect, this disclosure provides an antibody or antigen-binding fragment that binds to α7β1 integrin, wherein the antibody comprises HCDR1 of SEQ ID NO: 101, HCDR2 of SEQ ID NO: 102, HCDR3 of SEQ ID NO: 104, LCDR1 of SEQ ID NO: 105, LCDR2 of SEQ ID NO: 197, and LCDR3 of SEQ ID NO: 75.

[0055] In one aspect, this disclosure provides an antibody or antigen-binding fragment that binds to α7β1 integrin, wherein the antibody comprises HCDR1 of SEQ ID NO: 101, HCDR2 of SEQ ID NO: 102, HCDR3 of SEQ ID NO: 190, LCDR1 of SEQ ID NO: 105, LCDR2 of SEQ ID NO: 106, and LCDR3 of SEQ ID NO: 198.

[0056] In one aspect, this disclosure provides an antibody or antigen-binding fragment that binds to α7β1 integrin, wherein the antibody comprises HCDR1 of SEQ ID NO: 101, HCDR2 of SEQ ID NO: 102, HCDR3 of SEQ ID NO: 189, LCDR1 of SEQ ID NO: 105, LCDR2 of SEQ ID NO: 197, and LCDR3 of SEQ ID NO: 107.

[0057] In one aspect, this disclosure provides an antibody or antigen-binding fragment that binds to α7β1 integrin, wherein the antibody or antigen-binding fragment comprises:

[0058] i) The variable heavy region containing the amino acid sequence of SEQ ID NO: 128 and the light chain variable region containing the amino acid sequence of SEQ ID NO: 129;

[0059] ii) The variable heavy region comprising the amino acid sequence of SEQ ID NO: 130, and the light chain variable region comprising the amino acid sequence of SEQ ID NO: 131;

[0060] iii) The variable heavy region containing the amino acid sequence of SEQ ID NO: 132, and the light chain variable region containing the amino acid sequence of SEQ ID NO: 133;

[0061] iv) The variable heavy region containing the amino acid sequence of SEQ ID NO: 134, and the light chain variable region containing the amino acid sequence of SEQ ID NO: 135;

[0062] v) A variable heavy region comprising the amino acid sequence of SEQ ID NO: 136, and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 137;

[0063] vi) The variable heavy region comprising the amino acid sequence of SEQ ID NO: 138, and the light chain variable region comprising the amino acid sequence of SEQ ID NO: 139; or

[0064] vii) The variable heavy region containing the amino acid sequence of SEQ ID NO: 140, and the light chain variable region containing the amino acid sequence of SEQ ID NO: 141.

[0065] In one aspect, this disclosure provides an antibody or antigen-binding fragment that binds to α7β1 integrin, wherein the antibody or antigen-binding fragment comprises:

[0066] i) a heavy chain containing the amino acid sequence of SEQ ID NO: 118 and a light chain containing the amino acid sequence of SEQ ID NO: 119; a heavy chain containing the amino acid sequence of SEQ ID NO: 120 and a light chain containing the amino acid sequence of SEQ ID NO: 121;

[0067] ii) The variable heavy region comprising the amino acid sequence of SEQ ID NO: 199, and the light chain variable region comprising the amino acid sequence of SEQ ID NO: 200;

[0068] iii) The variable heavy region containing the amino acid sequence of SEQ ID NO: 201, and the light chain variable region containing the amino acid sequence of SEQ ID NO: 202;

[0069] iv) The variable heavy region containing the amino acid sequence of SEQ ID NO: 203, and the light chain variable region containing the amino acid sequence of SEQ ID NO: 204;

[0070] v) A variable heavy region comprising the amino acid sequence of SEQ ID NO: 205, and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 206;

[0071] vi) The variable heavy region containing the amino acid sequence of SEQ ID NO: 207 and the light chain variable region containing the amino acid sequence of SEQ ID NO: 208;

[0072] vii) The variable heavy region containing the amino acid sequence of SEQ ID NO: 209, and the light chain variable region containing the amino acid sequence of SEQ ID NO: 210;

[0073] viii) The variable heavy region containing the amino acid sequence of SEQ ID NO: 211, and the light chain variable region containing the amino acid sequence of SEQ ID NO: 212;

[0074] ix) a variable heavy region comprising the amino acid sequence of SEQ ID NO: 213, and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 214;

[0075] x) The variable heavy region containing the amino acid sequence of SEQ ID NO: 215, and the light chain variable region containing the amino acid sequence of SEQ ID NO: 216;

[0076] xi) The variable heavy region containing the amino acid sequence of SEQ ID NO: 217, and the light chain variable region containing the amino acid sequence of SEQ ID NO: 218;

[0077] xii) The variable heavy region comprising the amino acid sequence of SEQ ID NO: 219, and the light chain variable region comprising the amino acid sequence of SEQ ID NO: 220;

[0078] xiii) The variable heavy region comprising the amino acid sequence of SEQ ID NO: 221, and the light chain variable region comprising the amino acid sequence of SEQ ID NO: 222; or

[0079] xiv) The variable heavy region containing the amino acid sequence of SEQ ID NO: 223 and the light chain variable region containing the amino acid sequence of SEQ ID NO: 224.

[0080] In one aspect, this disclosure provides an antibody or antigen-binding fragment that binds to α7β1 integrin, wherein the antibody or antigen-binding fragment comprises:

[0081] i) The variable heavy region containing the amino acid sequence of SEQ ID NO: 142 and the light chain variable region containing the amino acid sequence of SEQ ID NO: 143;

[0082] ii) The variable heavy region containing the amino acid sequence of SEQ ID NO: 144, and the light chain variable region containing the amino acid sequence of SEQ ID NO: 145;

[0083] iii) The variable heavy region containing the amino acid sequence of SEQ ID NO: 146, and the light chain variable region containing the amino acid sequence of SEQ ID NO: 147;

[0084] iv) The variable heavy region comprising the amino acid sequence of SEQ ID NO: 148, and the light chain variable region comprising the amino acid sequence of SEQ ID NO: 149;

[0085] v) A variable heavy region comprising the amino acid sequence of SEQ ID NO: 150, and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 151;

[0086] vi) The variable heavy region containing the amino acid sequence of SEQ ID NO: 152 and the light chain variable region containing the amino acid sequence of SEQ ID NO: 153;

[0087] vii) The variable heavy region containing the amino acid sequence of SEQ ID NO: 154, and the light chain variable region containing the amino acid sequence of SEQ ID NO: 155;

[0088] viii) The variable heavy region containing the amino acid sequence of SEQ ID NO: 156, and the light chain variable region containing the amino acid sequence of SEQ ID NO: 157;

[0089] ix) a variable heavy region comprising the amino acid sequence of SEQ ID NO: 158, and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 159;

[0090] x) A variable heavy region containing the amino acid sequence of SEQ ID NO: 160, and a light chain variable region containing the amino acid sequence of SEQ ID NO: 161;

[0091] xi) The variable heavy region containing the amino acid sequence of SEQ ID NO: 162, and the light chain variable region containing the amino acid sequence of SEQ ID NO: 163;

[0092] xii) The variable heavy region comprising the amino acid sequence of SEQ ID NO: 164, and the light chain variable region comprising the amino acid sequence of SEQ ID NO: 165;

[0093] xiii) The variable heavy region containing the amino acid sequence of SEQ ID NO: 166 and the light chain variable region containing the amino acid sequence of SEQ ID NO: 167;

[0094] xiv) The variable heavy region containing the amino acid sequence of SEQ ID NO: 170, and the light chain variable region containing the amino acid sequence of SEQ ID NO: 171;

[0095] xv) a variable heavy region containing the amino acid sequence of SEQ ID NO: 172, and a light chain variable region containing the amino acid sequence of SEQ ID NO: 173; or

[0096] xvi) contains a variable heavy region of the amino acid sequence of SEQ ID NO: 186 and a light chain variable region of the amino acid sequence of SEQ ID NO: 187.

[0097] In one aspect, this disclosure provides an antibody or antigen-binding fragment that binds to α7β1 integrin, wherein the antibody or antigen-binding fragment comprises:

[0098] i) The variable heavy region containing the amino acid sequence of SEQ ID NO: 108 and the light chain variable region containing the amino acid sequence of SEQ ID NO: 109;

[0099] ii) The variable heavy region containing the amino acid sequence of SEQ ID NO: 110 and the light chain variable region containing the amino acid sequence of SEQ ID NO: 111.

[0100] In one aspect, this disclosure provides an antibody or antigen-binding fragment that binds to α7β1 integrin, wherein the antibody or antigen-binding fragment comprises:

[0101] i) a heavy chain containing the amino acid sequence of SEQ ID NO: 112, and a light chain containing the amino acid sequence of SEQ ID NO: 113;

[0102] ii) a heavy chain containing the amino acid sequence of SEQ ID NO: 114, and a light chain containing the amino acid sequence of SEQ ID NO: 113;

[0103] iii) A heavy chain containing the amino acid sequence of SEQ ID NO: 115, and a light chain containing the amino acid sequence of SEQ ID NO: 116; or

[0104] iv) The heavy chain containing the amino acid sequence of SEQ ID NO: 117, and the light chain containing the amino acid sequence of SEQ ID NO: 116.

[0105] In some embodiments, the antibody or antigen-binding fragment has an affinity (Kd) for α7β1 integrin or a fragment thereof between about 0.1 nM and 30 nM. In some embodiments, the antibody or antigen-binding fragment has an affinity (Kd) for α7β1 integrin or a fragment thereof between about 0.5 nM and 30 nM. In some embodiments, the α7β1 integrin or a fragment thereof comprises an α7β1 extracellular domain, a B1 extracellular domain, an a7 leg, a calf-1 domain, a calf-2 domain, or both a calf-1 domain and a calf-2 domain. In some embodiments, the α7β1 integrin or a fragment thereof comprises an α7β1 extracellular domain. In some embodiments, the α7β1 integrin or a fragment thereof comprises a B1 extracellular domain. In some embodiments, the α7β1 integrin or a fragment thereof comprises an a7 leg. In some embodiments, the α7β1 integrin or a fragment thereof comprises a calf-1 domain. In some embodiments, the α7β1 integrin or a fragment thereof includes a calf-2 domain. In some embodiments, the α7β1 integrin or a fragment thereof includes both a calf-1 domain and a calf-2 domain.

[0106] In some embodiments, the α7β1 integrin comprises human α7β1 integrin. In some embodiments, the antibody or antigen-binding fragment has an affinity of about 3 nM to 6 nM for the human α7β1 extracellular domain.

[0107] In some embodiments, the antibody or antigen-binding fragment activates the α7β1 integrin with a maximum efficacy (Emax) between 100% and 300% compared to the 20TFT antibody. In some embodiments, the antibody or antigen-binding fragment activates the α7β1 integrin with a maximum efficacy (Emax) between 100% and 300% compared to the TS2 / 16 antibody.

[0108] In some embodiments, the antibody or antigen-binding fragment has an EC50 value between 0.3 nM and 50 nM. In some embodiments, the antibody or antigen-binding fragment has an EC50 value of about 0.3 nM. In some embodiments, the antibody or antigen-binding fragment has an EC50 value between 0.3 nM and 1 nM. In some embodiments, the antibody or antigen-binding fragment has an EC50 value between 0.3 nM and 5 nM. In some embodiments, the antibody or antigen-binding fragment has an EC50 value between 0.3 nM and 10 nM. In some embodiments, the antibody or antigen-binding fragment has an EC50 value between 1 nM and 5 nM. In some embodiments, the antibody or antigen-binding fragment has an EC50 value between 1 nM and 10 nM. In some embodiments, the antibody or antigen-binding fragment has an EC50 value between 5 nM and 10 nM. In some embodiments, the antibody or antigen-binding fragment has an EC50 value between 5 nM and 50 nM. In some implementations, the antibody or antigen-binding fragment has an EC50 value between 10 nM and 50 nM.

[0109] In some embodiments, the antibody or antigen-binding fragment comprises Fab, a single-chain Fv (scFv), a single-domain antibody (sdAb), a VHH, one or more CDRs, a variable heavy chain (VH), a variable light chain (VL), a Fab-like bispecific antibody (bsFab), a single-domain antibody-linked Fab (s-Fab), an antibody, or a combination thereof. In some embodiments, the antibody or antigen-binding fragment comprises Fab. In some embodiments, the antibody or antigen-binding fragment comprises a single-chain Fv (scFv). In some embodiments, the antibody or antigen-binding fragment comprises a single-domain antibody (sdAb). In some embodiments, the antibody or antigen-binding fragment comprises a VHH. In some embodiments, the antibody or antigen-binding fragment comprises one or more CDRs. In some embodiments, the antibody or antigen-binding fragment comprises a variable heavy chain (VH). In some embodiments, the antibody or antigen-binding fragment comprises a variable light chain (VL). In some embodiments, the antibody or antigen-binding fragment comprises a Fab-like bispecific antibody (bsFab). In some embodiments, the antibody or antigen-binding fragment comprises a single-domain antibody-linked Fab (s-Fab). In some implementations, the antibody or antigen-binding fragment contains an antibody.

[0110] In some embodiments, the antibody or antigen-binding fragment is a humanized antibody. In some embodiments, the antibody or antigen-binding fragment is a human antibody. In some embodiments, the antibody or antigen-binding fragment is a chimeric antibody.

[0111] In some embodiments, the antibody or antigen-binding fragment is derived from IgG. In some embodiments, the antibody or antigen-binding fragment is derived from IgG1, IgG2, IgG3, or IgG4. In some embodiments, the antibody or antigen-binding fragment is derived from IgG1. In some embodiments, the antibody or antigen-binding fragment is derived from IgG2. In some embodiments, the antibody or antigen-binding fragment is derived from IgG3. In some embodiments, the antibody or antigen-binding fragment is derived from IgG4.

[0112] In some embodiments, the antibody or antigen-binding fragment includes an Fc region. In some embodiments, the Fc region contains one or more mutations.

[0113] In some embodiments, this disclosure provides a method for treating a subject for a disease or disorder associated with a deficiency of α7β1 integrin. In some embodiments, the method includes administering an antibody or antigen-binding fragment of this disclosure to the subject.

[0114] In some embodiments, the disease or disorder associated with α7β1 integrin deficiency includes cardiomyopathy in obese patients, congestive heart failure, muscular dystrophy, muscle atrophy, and lean muscle loss induced by GLP-1 receptor and GIP / GLP-1 receptor agonism. In some embodiments, the disease or disorder associated with α7β1 integrin deficiency includes cardiomyopathy. In some embodiments, the disease or disorder associated with α7β1 integrin deficiency includes congestive heart failure. In some embodiments, the disease or disorder associated with α7β1 integrin deficiency includes muscular dystrophy. In some embodiments, the disease or disorder associated with α7β1 integrin deficiency includes muscle atrophy. In some embodiments, the disease or disorder associated with α7β1 integrin deficiency includes sarcopenia.

[0115] In some implementations, administration of the antibody or antigen-binding fragment to the subject results in improvement of one or more symptoms of the muscular dystrophy.

[0116] In some embodiments, one or more serum biomarkers that reduce myofibrous damage are administered. In some embodiments, the one or more serum biomarkers comprise creatine kinase, cytotoxic LDH, and / or IL-6. In some embodiments, the serum biomarker comprises creatine kinase. In some embodiments, the serum biomarker comprises cytotoxic LDH. In some embodiments, the serum biomarker comprises IL-6.

[0117] In some embodiments, the application reduces muscle damage, inflammation, fibrosis, necrosis, and / or atrophy. In some embodiments, the application reduces muscle damage. In some embodiments, the application reduces inflammation. In some embodiments, the application reduces fibrosis. In some embodiments, the application reduces necrosis. In some embodiments, the application reduces atrophy.

[0118] In some embodiments, the administration of the antibody or antigen-binding fragment is targeted at muscle cells. In some embodiments, the muscle cells contain a mutation in the dystrophin gene. In some embodiments, the muscle cells lack dystrophin. In some embodiments, the muscle cells contain non-functional dystrophin.

[0119] In some embodiments, the muscular dystrophy includes Duchenne muscular dystrophy, Becker muscular dystrophy, limb-girdle muscular dystrophy, Fukuyama congenital muscular dystrophy (FCMD), or regional muscular dystrophy type 1A (MDC1A). In some embodiments, the muscular dystrophy includes Duchenne muscular dystrophy. In some embodiments, the muscular dystrophy includes Becker muscular dystrophy. In some embodiments, the muscular dystrophy includes limb-girdle muscular dystrophy. In some embodiments, the muscular dystrophy includes Fukuyama congenital muscular dystrophy (FCMD). In some embodiments, the muscular dystrophy includes regional muscular dystrophy type 1A (MDC1A).

[0120] In some embodiments, the muscle atrophy is due to aging, inactivity, denervation, or other underlying conditions, including chronic obstructive pulmonary disease, cancer-related cachexia, diabetes, kidney failure, and heart failure. In some embodiments, the muscle atrophy is due to aging. In some embodiments, the muscle atrophy is due to inactivity. In some embodiments, the muscle atrophy is due to denervation. In some embodiments, the muscle atrophy is due to other underlying conditions.

[0121] In some implementations, the loss of lean muscle mass in obese patients treated with glucagon-like peptide-1 receptor agonists.

[0122] In some implementations, the heart failure is due to hereditary cardiomyopathy. In other implementations, the heart failure is due to ischemic heart disease.

[0123] In some embodiments, this disclosure provides a pharmaceutical composition comprising an antibody or antigen-binding fragment and a pharmaceutically acceptable carrier. In some embodiments, the antibody or antigen-binding fragment is administered parenterally. In some embodiments, the antibody or antigen-binding fragment is administered orally.

[0124] In some embodiments, the antibody or antigen-binding fragment is administered intravenously. In some embodiments, the antibody or antigen-binding fragment is administered intradermally. In some embodiments, the antibody or antigen-binding fragment is administered transdermally. In some embodiments, the antibody or antigen-binding fragment is administered intraocularly. In some embodiments, the antibody or antigen-binding fragment is administered subcutaneously. In some embodiments, the antibody or antigen-binding fragment is administered via a mucosa.

[0125] In some embodiments, this disclosure provides a method for treating cardiomyopathy, congestive heart failure, or other myocardial disorders by administering an antibody or antigen-binding fragment to a subject.

[0126] In one aspect, this disclosure provides in particular a method for treating muscular dystrophy in a subject, the method comprising administering a pharmaceutical composition to the subject in need, the pharmaceutical composition comprising: an antibody functional unit for promoting the extended-open conformation of α7β1 integrin; and one or more physiologically acceptable carriers, excipients, or diluents.

[0127] In one aspect, this disclosure provides in particular a method for treating muscle atrophy in a subject, the method comprising administering a therapeutic agent to the subject in need to increase the expression of α7, wherein the increase in α7 expression leads to improvement in one or more symptoms of muscle atrophy. In some embodiments, the therapeutic agent comprises an antibody or antigen-binding fragment of this disclosure.

[0128] In one aspect, this disclosure provides in particular a method for treating muscle atrophy in a subject, the method comprising administering to the subject in need a pharmaceutical composition comprising an antibody or antigen-binding fragment of this disclosure, wherein the administration results in improvement of one or more symptoms of muscle atrophy.

[0129] In some implementations, after administration of the antibody or its binding fragment, the subject exhibited reduced muscle loss compared to a control.

[0130] In some embodiments, after administration of the antibody or its binding fragment, the subject exhibits a muscle mass change of less than 40% compared to a control. In some embodiments, after administration of the antibody or its binding fragment, the subject exhibits a muscle mass change of less than 35% compared to a control. In some embodiments, after administration of the antibody or its binding fragment, the subject exhibits a muscle mass change of less than 30% compared to a control. In some embodiments, after administration of the antibody or its binding fragment, the subject exhibits a muscle mass change of less than 28% compared to a control. In some embodiments, after administration of the antibody or its binding fragment, the subject exhibits a muscle mass change of less than 27% compared to a control. In some embodiments, after administration of the antibody or its binding fragment, the subject exhibits a muscle mass change of less than 26% compared to a control. In some embodiments, after administration of the antibody or its binding fragment, the subject exhibits a muscle mass change of less than 25% compared to a control. In some embodiments, after administration of the antibody or its binding fragment, the subject exhibits a muscle mass change of less than 24% compared to a control. In some embodiments, after administration of the antibody or its binding fragment, the subject showed a muscle mass change of less than 23% compared to a control. In some embodiments, after administration of the antibody or its binding fragment, the subject showed a muscle mass change of less than 22% compared to a control. In some embodiments, after administration of the antibody or its binding fragment, the subject showed a muscle mass change of less than 21% compared to a control. In some embodiments, after administration of the antibody or its binding fragment, the subject showed a muscle mass change of less than 20% compared to a control. In some embodiments, after administration of the antibody or its binding fragment, the subject showed a muscle mass change of less than 19% compared to a control. In some embodiments, after administration of the antibody or its binding fragment, the subject showed a muscle mass change of less than 18% compared to a control. In some embodiments, after administration of the antibody or its binding fragment, the subject showed a muscle mass change of less than 17% compared to a control. In some embodiments, after administration of the antibody or its binding fragment, the subject showed a muscle mass change of less than 16% compared to a control. In some embodiments, after administration of the antibody or its binding fragment, the subject experienced a muscle mass change of less than 15% compared to a control. In some embodiments, after administration of the antibody or its binding fragment, the subject experienced a muscle mass change of less than 14% compared to a control. In some embodiments, after administration of the antibody or its binding fragment, the subject experienced a muscle mass change of less than 13% compared to a control. In some embodiments, after administration of the antibody or its binding fragment, the subject experienced a muscle mass change of less than 12% compared to a control.In some embodiments, after administration of the antibody or its binding fragment, the subject exhibits a muscle mass change of less than 11% compared to a control. In some embodiments, after administration of the antibody or its binding fragment, the subject exhibits a muscle mass change of less than 10% compared to a control. In some embodiments, after administration of the antibody or its binding fragment, the subject exhibits a muscle mass change of less than 9% compared to a control. In some embodiments, after administration of the antibody or its binding fragment, the subject exhibits a muscle mass change of less than 8% compared to a control. In some embodiments, after administration of the antibody or its binding fragment, the subject exhibits a muscle mass change of less than 7% compared to a control. In some embodiments, after administration of the antibody or its binding fragment, the subject exhibits a muscle mass change of less than 6% compared to a control. In some embodiments, after administration of the antibody or its binding fragment, the subject exhibits a muscle mass change of less than 5% compared to a control. In some embodiments, after administration of the antibody or its binding fragment, the subject exhibits a muscle mass change of less than 4% compared to a control. In some embodiments, after administration of the antibody or its binding fragment, the subject experienced a change in muscle mass of less than 3% compared to a control. In some embodiments, after administration of the antibody or its binding fragment, the subject experienced a change in muscle mass of less than 2% compared to a control. In some embodiments, after administration of the antibody or its binding fragment, the subject experienced a change in muscle mass of less than 1% compared to a control.

[0131] In some implementations, the control is a baseline value prior to the administration of the antibody or its binding fragment.

[0132] In some implementations, the comparison is historical data.

[0133] In some implementations, the control group is a comparable subject who has not been given the antibody or its antigen-binding fragment.

[0134] In one aspect, this disclosure provides in particular a method of treating muscle atrophy in a subject, the method comprising administering a pharmaceutical composition to the subject in need, the pharmaceutical composition comprising (a) an antibody functional unit for stabilizing the extended conformation of α7β1 integrin and (b) one or more physiologically acceptable carriers. In some embodiments, the antibody functional unit for stabilizing the extended conformation of α7β1 integrin comprises an antibody or antigen-binding fragment of this disclosure.

[0135] In one aspect, this disclosure provides a method for treating muscle atrophy in a subject, the method comprising administering a pharmaceutical composition to the subject in need, the pharmaceutical composition comprising (a) an antibody functional unit for increasing α7 expression and (b) one or more physiologically acceptable carriers. In some embodiments, the antibody functional unit for increasing α7 expression comprises an antibody or antigen-binding fragment of this disclosure. Attached Figure Description

[0136] The accompanying drawings are for illustrative purposes only and are not intended to be limiting.

[0137] Figure 1A The α7β1 integrin domain is shown for use in the production of the disclosed antibody. Figures 1B to 1D These are a series of exemplary graphs showing the binding affinity of exemplary anti-α7β1 antibodies to different α7β1 domains, as determined by ELISA assays. In particular, the binding of exemplary antibodies Ab2, Ab8, and RefAb1 to the extracellular domain, leg domain, and calf-1 domain of α7β1 was tested.

[0138] Figure 2 Exemplary competitive ELISA assays showing the binding of Ab2 and RefAb1 to the extracellular domain of human α7β1 are presented.

[0139] Figure 3 These are a series of exemplary graphs illustrating the results of competitive ELISA assays that determine whether an exemplary human anti-α7β1 antibody has an epitope that overlaps with Ab2, Ab8, or RefAb1.

[0140] Figure 4 The results of a competitive ELISA assay that determines whether an exemplary mouse anti-α7β1 antibody has an epitope that overlaps with Ab8 or RefAb1 are shown.

[0141] Figure 5A is an exemplary schematic diagram showing the bent-closed conformation of integrin α7β1, which has a low binding affinity for laminin. Figure 5B is an exemplary schematic diagram showing the extended-closed conformation of integrin α7β1, which has a low binding affinity for laminin, and how the exemplary anti-α7β1 and antibody of this disclosure bind to integrin α7β1 to stabilize this conformation. Figure 5C is an exemplary schematic diagram showing the extended-open conformation of integrin α7β1, which has a high binding affinity for laminin, and how the exemplary anti-α7β1 and antibody of this disclosure bind to integrin α7β1 to stabilize this conformation.

[0142] Figure 6These are exemplary crystal structures of the α7 leg disclosed in this disclosure and epitopes of different antibodies. In particular, Ab8 binds to Calf-1, and Ab2 binds to a region in the Calf-2 domain that is different from the epitope of the RefAb1 (20TFT) antibody.

[0143] Figure 7 These are a series of electron microscope images of exemplary anti-α7β1 antibodies that bind to integrin α7β1, and their cartoon representations.

[0144] Figure 8A It is an exemplary crystal structure of Ab2 heavy chain (orange) and light chain (yellow) complexed with α7 calf-1 (blue). Figure 8B The biomolecular interactions within the Ab2 Fab-α7 calf-1 complex are shown. The calf-1 protein is blue and displayed alongside Ab2 HCDR1 (pink), HCDR2 (orange), HCDR3 (green), and LCDR1 (yellow). Figure 8C The amino acid sequence of the α7 protein is shown, with epitope residues highlighted.

[0145] Figure 9 This is an exemplary diagram depicting a structural model of the α7β1 in the α7 leg, where the epitope of the Ab2 antibody may be located within the sphere. The corresponding amino acid residues are highlighted in SEQ ID NO: 180. Residues highlighted in magenta (MAIPQQL, SEQ ID NO: 181; VVRGERAMQSERDVGSKVKYEVT, SEQ ID NO: 182; FDRAAVL, SEQ ID NO: 183) illustrate one possible epitope, and residues highlighted in red (LRTLGSAFL, SEQ ID NO: 184; VVFSCPLYS, SEQ ID NO: 185) represent another possible epitope. Epitope residues were determined by hydrogen / deuterium exchange mass spectrometry.

[0146] Figure 10 This is an exemplary diagram showing the effect of activation conditions (i.e., conditions that stabilize the open conformation of integrin α7β1) on the cell binding of the exemplary anti-α7β1 antibody of this disclosure to human DMD myoblasts.

[0147] Figure 11 This is an exemplary graph showing the effect of activation conditions on cell binding to anti-α7β1 in an exemplary mouse compared to RefAb1.

[0148] Figure 12 This is an exemplary bar chart showing the levels of creatine kinase (CKM) (a muscle damage indicator) after a short treadmill run in a mouse MDX model, with and without the application of an exemplary anti-α7β1 antibody.

[0149] Figure 13 This is an exemplary graph showing the dose response of CKM and LDH to the application of the exemplary anti-α7β1 antibody Ab8.

[0150] Figure 14 The biological process upregulated by applying an exemplary anti-α7β1 antibody is shown.

[0151] Figure 15 The biological process downregulated by applying an exemplary anti-α7β1 antibody is shown.

[0152] Figure 16A and Figure 16B These are a series of exemplary graphs showing the increase in gene expression caused by the application of an exemplary anti-α7β1 antibody.

[0153] Figure 17 This is an exemplary graph showing the running score and total running distance of B10.mdx mice after administration of an exemplary anti-α7β1 antibody.

[0154] Figure 18 This is an exemplary graph showing the walking distance, resting time, and horizontal beam interruption count of MDX mice administered an exemplary anti-α7β1 antibody.

[0155] Figure 19A This is an exemplary diagram showing specific tetanus in the extensor digitorum longus muscle of MDX mice treated with the exemplary α7β1 antibody and a control. Figure 19B Specific tetanus in the diaphragm of MDX mice treated with exemplary α7β1 antibody and control mice is shown.

[0156] Figure 20 This is an exemplary graph showing the results of tracking the body weight of MDX mice with and without the administration of the exemplary anti-α7β1 antibody.

[0157] Figure 21 This is an exemplary graph showing the muscle fiber size from MDX mice treated with and without the exemplary anti-α7β1 antibody.

[0158] Figure 22A These are a series of exemplary graphs showing the qPCR results of tracking fibrosis markers in MDX mice after administration of an exemplary anti-α7β1 antibody. Figure 22B Exemplary immunohistochemical images of collagen I / III and quantitative areas of positive collagen I / III are provided for mice treated with PBS or Ab8. Lower collagen levels are a marker of less scar tissue and fibrosis, which is a visible difference that can be seen in histological images.

[0159] Figure 23This is an exemplary schematic diagram of a research design for assessing the reduction of muscle atrophy by administering an exemplary anti-α7β1 antibody.

[0160] Figure 24 These are a series of exemplary graphs showing the muscle weight of the gastrocnemius-soleus complex (Gastroc) in C57BL / 6j mice after administration of an exemplary anti-α7β1 antibody in VIM. Disuse atrophy induced by VIM results in a loss of muscle weight in the Gastroc, both in absolute and relative to body weight.

[0161] Figure 25 These are a series of exemplary graphs showing the expression of α7 after administration of an exemplary anti-α7β1 antibody to C57BL / 6j mice in VIM, compared to the free-movement control group.

[0162] definition

[0163] To facilitate a better understanding of the invention, certain terms are defined below. Additional definitions for the following terms and other terms are set forth throughout the specification.

[0164] "Relief" and "improvement" refer to the process of reducing the severity of signs or symptoms of a disorder. Importantly, signs or symptoms can be relieved rather than eliminated. An effective dose of treatment is expected to reduce the severity of signs or symptoms of the disease, and thus alleviate and improve them.

[0165] As used herein, the term "affinity" refers to the characteristic of the binding interaction between the binding moiety (e.g., an integrin α7β1 antibody) and the target (e.g., α7β1), and it indicates the strength of the binding interaction. In some embodiments, the measure of affinity is expressed as the dissociation constant (KD).

[0166] As used herein, the term "antibody" refers to a polypeptide that includes at least one immunoglobulin variable region, such as an amino acid sequence providing an immunoglobulin variable domain or an immunoglobulin variable domain sequence. For example, an antibody may include a heavy (H) chain variable region (abbreviated herein as VH) and a light (L) chain variable region (abbreviated herein as VL). In another example, an antibody includes two heavy (H) chain variable regions and two light (L) chain variable regions. Antibodies typically include three complementarity-determining regions (CDRs) in the light chain of an immunoglobulin and three complementarity-determining regions (CDRs) in the heavy chain of an immunoglobulin. The three CDRs in the light chain of an immunoglobulin are referred to as CDR1, CDR2, and CDR3, respectively, from the N-terminal side. The three CDRs in the heavy chain of an immunoglobulin are also referred to as CDR1, CDR2, and CDR3, respectively, from the N-terminal side. "CDR" may be identified according to the definitions of Kabat and Chothia, the accumulation of both Kabat and Chothia, AbM, contact and / or conformation definitions, or any CDR assay method well known in the art. The term "antibody" encompasses antigen-binding fragments of antibodies (e.g., single-chain antibodies, Fab, F(ab')2, Fd, Fv, and dAb fragments) as well as intact antibodies, such as IgA, IgG, IgE, IgD, and IgM types (and their subtypes) of complete immunoglobulins. The light chain of an immunoglobulin can be κ or λ type.

[0167] As used herein, the term "M38 antibody" refers to a mouse anti-α7β1 antibody that binds to S977, W978, W979, and P980 of the α7 integrin, as described in WO2022240833A1, which is incorporated herein by reference. In this application, "M38" and "RefAb2" are used interchangeably.

[0168] As used herein, the term "20TFT antibody" refers to an anti-α7β1 antibody binding to S977, W978, W979, and P980 of the α7 integrin, as described in WO 2021 / 097338 A1, which is hereby incorporated by reference. The 20TFT antibody is a humanized antibody against M38. In this application, "20TFT" and "RefAb1" are used interchangeably.

[0169] As used herein, the term "EC50" refers to the half-maximum effective concentration. EC50 refers to the concentration of a drug, antibody, or toxin that induces a response between baseline and maximum value after a specified exposure time. More simply, EC50 can be defined as the concentration required to achieve 50% of the desired effect.

[0170] As used herein, the term "Fab" refers to an antibody fragment that contains a portion of a complete antibody, including its antigen-binding region or variable region.

[0171] As used herein, the term "Fc region" refers to the C-terminal region of an immunoglobulin heavy chain that contains at least a portion of the constant region. This term includes native sequence Fc regions and variant Fc regions. In one embodiment, the human IgG heavy chain Fc region extends from Cys226 or Pro230 to the C-terminus of the heavy chain. However, the C-terminal lysine residue (Lys447) of the Fc region may or may not be present. Unless otherwise stated herein, the amino acid residues in the Fc region or constant region 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.

[0172] As used herein, the term “EC50” refers to the concentration required to inhibit half of the maximum biological response to ligand binding and can be determined by cell adhesion assay (CAA) or solid phase assay (SP).

[0173] As used herein, the term "identity" refers to the relationship between the sequences of two or more polypeptide molecules or two or more nucleic acid molecules as known in the art, by comparing the sequences of these molecules. Relationships are determined by doing so. In the art, "identity" also means the degree of sequence correlation between nucleic acid molecules or polypeptides, and in some cases, more than one nucleotide sequence or more than one. It can be determined by matching between amino acid sequence strings. "Identity" also refers to the gap alignment (if any) solved by a particular mathematical model or computer program (i.e., "algorithm") between the smaller sequence of two or more sequences. The percentage of identity matches is measured.

[0174] As used herein, the term “in vitro” refers to events that occur in an artificial environment (e.g., in test tubes or reaction vessels, in cell cultures, etc.) rather than in a multicellular organism.

[0175] As used herein, the term "in vivo" refers to events that occur within a multicellular organism, such as humans and non-human animals. In the context of cell-based systems, the term can be used to refer to events that occur within living cells (as opposed to, for example, in vitro systems).

[0176] "Integrin activator" or "integrin α7β1 activator" refers to a molecule that can bind to integrin α7β1 in a manner that increases one or more activities associated with integrin. For example, but not limited to, an integrin α7β1 activator can increase the binding of integrin α7β1 to laminin. In some embodiments, the integrin α7β1 activator is an anti-α7β1 antibody.

[0177] As used herein, the term "treatment" means any method used to partially or completely reduce, improve, alleviate, suppress, prevent, delay the onset of one or more symptoms characteristic of a particular disease, disorder, and / or condition, or reduce the severity and / or incidence of one or more symptoms characteristic of a particular disease, disorder, and / or condition. Treatment may be administered to subjects who do not show signs of disease and / or only show early signs of disease to reduce the risk of developing a pathology associated with the disease. Detailed Implementation

[0178] This disclosure specifically provides the therapeutic use of integrin α7β1 antibodies and such antibodies in the effective treatment of diseases or disorders associated with loss of dystrophin, such as Duchenne muscular dystrophy (DMD). As described herein, this disclosure is partly based on the identification of integrin α7β1 antibodies that effectively stabilize the extended-closed or extended-open conformation of α7β1 integrin. Therefore, the anti-α7β1 antibodies of this disclosure effectively increase myofiber adhesion to the extracellular matrix, restore some or all of the muscle adhesion lost due to the deficiency of functional dystrophin, and ultimately improve motor function, increase muscle strength, and reduce fibrosis in patients with dystrophin-related diseases.

[0179] Integrin α7β1

[0180] The dystrophin-glycoprotein complex maintains skeletal muscle integrity by associating laminin in the extracellular matrix with the actin cytoskeleton. Several human muscular dystrophys are caused by defects in components of this complex. α7β1 integrin also binds to laminin and connects the extracellular matrix to the cytoskeleton. The α7β1 integrin complex apparently plays a role in the development of skeletal and smooth muscle. α7β1 integrin promotes myoblast adhesion and movement, and it may be important in the recruitment of myogenic precursors during muscle differentiation.

[0181] The dystrophin-associated protein complex (DAPC) and α7β1 integrin maintain the integrity of the myofibrous membrane. Repeated contraction and relaxation of the sarcomere require efficient handling of mechanical stress by the myofibrous membrane. Disruption of DAPC or α7β1 bonds leads to impaired association between the cell membrane and the endocrine disruptor (ECM), resulting in membrane damage due to excessive force loading. Furthermore, loss-of-function (LOF) mutations in dystrophin cause Duchenne muscular dystrophy (DMD), while LOF mutations in ITGA7 (the gene encoding α7β1 integrin) cause congenital muscular dystrophy.

[0182] Structure and conformation of integrin α7β1

[0183] The structure and conformation of integrins are crucial to every aspect of their function, from adhesion to signal transduction. α7β1 integrins can adopt a range of conformations: (Fig. 5A) a bent-closed conformation and an extended-closed conformation, which are inactive and have low affinity for laminins (Fig. 5B), and an extended-open conformation (Fig. 5C), which is active and has high affinity for laminins. The α7 subunit possesses the β-propeller domain, thigh domain, calf-1 domain, and calf-2 domain, as shown in Fig. 5C.

[0184] This disclosure particularly provides antibodies that bind to α7β1 integrin in either an extended-open or extended-closed conformation, enhancing the binding of α7β1 integrin to laminin. In some embodiments, the anti-α7β1 integrin antibody binds to α7β1 integrin in an extended-closed conformation. In some embodiments, the anti-α7β1 integrin antibody binds to α7β1 integrin in an extended-open conformation. In some embodiments, the anti-α7β1 integrin antibody maintains α7β1 integrin in an extended-closed conformation. In some embodiments, the anti-α7β1 integrin antibody maintains α7β1 integrin in an extended-open conformation.

[0185] The extracellular domain of human integrin α7 can exist in either the X1 or X2 isoform.

[0186] In some implementations, the extracellular domain of human integrin α7 has the following amino acid sequence (signal peptide underlined):

[0187] MAGARSRDPWGASGICYLFGSLLVELLFSRAVA

[0188] In some implementations, the extracellular domain of human integrin α7 has the following amino acid sequence:

[0189]

[0190] In some implementations, the extracellular domain of human integrin α7 has the following amino acid sequence:

[0191]

[0192] The human α7 leg has the following amino acid sequence:

[0193] QGCGEDKICQSNLQLVRARFCTRVSDTEFQPLPMDVDGTTALFALSGQPVIGLEMVTNLPSDPAQPQADGDDAHEAQLLVMLPDSLHYSGVRALDPAEKPLCLSNENASHVECELGNPMKRGAQVTFYLILSTSGISIETTELEVELLLATISEQELHPVSARARVFIELPLSIAGMAIPQQLFFSGVVRGERAMQSERDV GSKVKYEVTVSNQGQSLRTLGSAFLNIMWPHEIANGKWLLYPMQVELEGGQGPGQKGLCSPRPNILHLDVDSRDRRRRELEPPEQQEPGERQEPSMSWWPVSSAEKKKNITLDCARGTANCVVFSCPLYSFDRAAVLHVWGRLWNSTFLEEYSAVKSLEVIVRANITVKSSIKNLMLRDASTVIPVMVYLDPMAVVAE (SEQ ID NO: 125, a7 leg)

[0194] The calf-1 domain of human α7 has the following amino acid sequence:

[0195] QSNLQLVRARFCTRVSDTEFQPLPMDVDGTTALFALSGQPVIGLEMVTNLPSDPAQPQADGDDAHEAQLLVMLPDSLHYSGVRALDPAEKPLCLSNENASHVECELGNPMKRGAQVTFYLILSTSGISIETTELEVELLLATISEQELHPVSARARVFIE (SEQ ID NO: 126, calf1)

[0196] The calf-2 domain of human α7 has the following amino acid sequence:

[0197] LPLSIAGMAIPQQLFFSGVVRGERAMQSERDVGSKVKYEVTVSNQGQSLRTLGSAFLNIMWPHEIANGKWLLYPMQVELEGGQGPGQKGLCSPRPNILHLDVDSRDRRRRELEPPEQ QEPGERQEPSMSWWPVSSAEKKKNITLDCARGTANCVVFSCPLYSFDRAAVLHVWGRLWNSTFLEEYSAVKSLEVIVRANITVKSSIKNLMLRDASTVIPVMVYLDPMAVVAE (SEQ ID NO: 127, calf2)

[0198] Integrin a7β1 antibody

[0199] This disclosure particularly provides an antibody or antigen-binding fragment thereof that binds to α7β1 integrin in either an extended-open or extended-closed conformation, thereby maintaining the high affinity of α7β1 integrin for laminin. Furthermore, the anti-α7β1 integrin antibody of this disclosure effectively promotes the adhesion of muscle cells to laminin.

[0200] In some embodiments, the anti-α7β1 integrin antibody activates α7β1 integrin. In some embodiments, the anti-α7β1 integrin antibody stabilizes the active conformation of α7β1 integrin. In some embodiments, the anti-α7β1 integrin antibody increases ITGA7 expression and / or the activity of α7β1 integrin. In some embodiments, the anti-α7β1 integrin antibody increases the activity of α7β1 integrin.

[0201] α7β1 integrin contains, for example, Figure 1A And the multiple domains shown in Figure 5C. In some embodiments, the anti-α7β1 integrin antibody binds to the leg of α7. In some embodiments, the anti-α7β1 integrin antibody binds to the laminin-binding domain. In some embodiments, the anti-α7β1 integrin antibody binds to the calf-1 domain and / or calf-2 domain of the α7β1 integrin. In some embodiments, the anti-α7β1 integrin antibody binds to the calf-1 domain of the α7β1 integrin. In some embodiments, the anti-α7β1 integrin antibody binds to the calf-2 domain of the α7β1 integrin.

[0202] Epitope

[0203] This disclosure is partly based on the identification of novel epitopes of α7 integrin. Anti-α7β1 antibodies binding to the epitopes described herein can effectively stabilize the extended conformation of α7β1 integrin, allowing α7β1 integrin to bind to laminin with high affinity and maintain its active form. Therefore, the agonistic anti-α7β1 integrin antibodies of this disclosure are effective in treating diseases associated with dystrophin, such as Duchenne muscular dystrophy (DMD).

[0204] In some embodiments, the anti-α7β1 integrin antibody binds to the calf-2 domain of the α7β1 integrin. In some embodiments, the anti-α7β1 integrin antibody binds to regions containing positions 856-862, 867-889, 1011-1017, 897-905, or 1002-1010 of integrin α7. In some embodiments, the anti-α7β1 integrin antibody binds to regions containing positions 856-862 of integrin α7. In some embodiments, the anti-α7β1 integrin antibody binds to regions containing positions 867-889 of integrin α7. In some embodiments, the anti-α7β1 integrin antibody binds to regions containing positions 1011-1017 of integrin α7. In some embodiments, the anti-α7β1 integrin antibody binds to regions containing positions 897-905 of integrin α7. In some embodiments, the anti-α7β1 integrin antibody binds to the region containing positions 1002-1010 of integrin α7. In some embodiments, the anti-α7β1 integrin antibody binds to the region containing amino acids M856, A857, I858, P859, Q860, Q861, L862, V867, V868, R869, G870, E871, R872, A873, M874, Q875, S876, E877, R878, D879, V880, G881, S882, K883, V884, K885, and Y886. Epitopes containing amino acids M887, V888, T889, L897, R898, T899, L900, G901, S902, A903, F904, L905, V1002, V1003, F1004, S1005, C1006, P1007, L1008, Y1009, S1010, F1011, D1012, R1013, A1014, A1015, V1016, and / or L1017. In some embodiments, the anti-α7β1 integrin antibody binds to epitopes containing amino acids M856, A857, I858, P859, Q860, Q861, and / or L862. In some embodiments, the anti-α7β1 integrin antibody binds to epitopes comprising amino acids V867, V868, R869, G870, E871, R872, A873, M874, Q875, S876, E877, R878, D879, V880, G881, S882, K883, V884, K885, Y886, E887, V888, and / or T889. In some embodiments, the anti-α7β1 integrin antibody binds to epitopes comprising amino acids L897, R898, T899, L900, G901, S902, A903, F904, and / or L905.In some embodiments, the anti-α7β1 integrin antibody binds to an epitope containing amino acids V1002, V1003, F1004, S1005, C1006, P1007, L1008, Y1009, and S1010. In some embodiments, the anti-α7β1 integrin antibody binds to an epitope containing amino acids F1011, D1012, R1013, A1014, A1015, V1016, and / or L1017.

[0205] In some embodiments, the anti-α7β1 integrin antibody binds to the calf-2 domain of the α7β1 integrin but does not compete with the 20TFT antibody. In some embodiments, the anti-α7β1 integrin antibody binds to the calf-2 domain of the α7β1 integrin but does not bind to epitopes containing amino acids S977, W978, W979, and P980.

[0206] In some embodiments, the anti-α7β1 integrin antibody binds to the calf-1 domain of the α7β1 integrin. In some embodiments, the anti-α7β1 integrin antibody binds to the region containing positions 771-778 or 793-805 of integrin α7. In some embodiments, the anti-α7β1 integrin antibody binds to the region containing positions 771-778 of integrin α7. In some embodiments, the anti-α7β1 integrin antibody binds to the region containing positions 793-805 of integrin α7. In some embodiments, the anti-α7β1 integrin antibody binds to an epitope comprising the amino acids R771, A772, L773, D774, P775, A776, E777, K778, E793, L794, G795, N796, P797, M798, K799, R800, G801, A802, Q803, V804, and / or T805. In some embodiments, the anti-α7β1 integrin antibody binds to an epitope comprising the amino acids R771, A772, L773, D774, A776, E777, K778, E793, N796, K799, Q803, and / or T805. In some implementations, the anti-α7β1 integrin antibody binds to an epitope containing amino acids R771, A772, L773, D774, A776, E777, K778, E793, N796, K799, Q803, and T805.

[0207] Human anti-α7β1 integrin antibody

[0208] In some embodiments, the integrin α7β1 antibody or antigen-binding fragment comprises at least one, two, or three complementarity-determining regions (CDRs) from the heavy chain variable region, which has an amino acid sequence as shown in Table A or a sequence substantially homologous to it (e.g., at least about 85%, 90%, 95%, 99% or more identical to it, and / or has one or more substitutions, such as conserved substitutions). In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises at least one, two, or three CDRs from the light chain variable region, which has an amino acid sequence as shown in Table A or a sequence substantially homologous to it (e.g., at least about 85%, 90%, 95%, 99% or more identical to it, and / or has one or more substitutions, such as conserved substitutions). In one embodiment, the integrin α7β1 antibody or its antigen-binding fragment comprises at least one, two, three, four, five, or six CDRs from the heavy chain variable region and the light chain variable region, the heavy chain variable region and the light chain variable region having amino acid sequences as shown in Table A or sequences substantially homologous to them (e.g., sequences that are at least about 85%, 90%, 95%, 99% or more identical to them, and / or have one or more substitutions, such as conserved substitutions).

[0209] In some embodiments, the antibody or its antigen-binding fragment is an anti-human α7β1 antibody. In some embodiments, the antibody or its antigen-binding fragment comprises a CDR selected from Table A. Unless otherwise stated, the CDR sequences shown in this application are in the IMGT numbering scheme.

[0210] Table A. Exemplary CDRs for Human Anti-α7β1 Antibodies .

[0211]

[0212] In some embodiments, the antibody or its antigen-binding fragment comprises HCDR1 of SEQ ID NO: 1 (HCDR1A), HCDR2 of SEQ ID NO: 15 (HCDR2A), and HCDR3 of SEQ ID NO: 31 (HCDR3A). In some embodiments, the antibody or its antigen-binding fragment comprises LCDR1 of SEQ ID NO: 46 (LCDR1A), LCDR2 of SEQ ID NO: 58 (LCDR2A), and LCDR3 of SEQ ID NO: 69 (LCDR3A). In some embodiments, the antibody or its antigen-binding fragment comprises HCDR1 of SEQ ID NO: 1 (HCDR1A), HCDR2 of SEQ ID NO: 15 (HCDR2A), HCDR3 of SEQ ID NO: 31 (HCDR3A), LCDR1 of SEQ ID NO: 46 (LCDR1A), LCDR2 of SEQ ID NO: 58 (LCDR2A), and LCDR3 of SEQ ID NO: 69 (LCDR3A).

[0213] In some embodiments, the antibody or its antigen-binding fragment competes with a reference antibody, wherein the reference antibody comprises HCDR1 of SEQ ID NO: 1 (HCDR1A), HCDR2 of SEQ ID NO: 15 (HCDR2A), HCDR3 of SEQ ID NO: 31 (HCDR3A), LCDR1 of SEQ ID NO: 46 (LCDR1A), LCDR2 of SEQ ID NO: 58 (LCDR2A), and LCDR3 of SEQ ID NO: 69 (LCDR3A).

[0214] In some embodiments, the antibody or its antigen-binding fragment comprises HCDR1 of SEQ ID NO: HCDR1B, HCDR2 of SEQ ID NO: 16 (HCDR2B), and HCDR3 of SEQ ID NO: 32 (HCDR3B). In some embodiments, the antibody or its antigen-binding fragment comprises LCDR1 of SEQ ID NO: 47 (LCDR1B), LCDR2 of SEQ ID NO: 59 (LCDR2B), and LCDR3 of SEQ ID NO: 70 (LCDR3B). In some embodiments, the antibody or its antigen-binding fragment comprises HCDR1 of SEQ ID NO: HCDR1B, HCDR2 of SEQ ID NO: 16 (HCDR2B), HCDR3 of SEQ ID NO: 32 (HCDR3B), LCDR1 of SEQ ID NO: 47 (LCDR1B), LCDR2 of SEQ ID NO: 59 (LCDR2B), and LCDR3 of SEQ ID NO: 70 (LCDR3B).

[0215] In some embodiments, the antibody or its antigen-binding fragment competes with a reference antibody, wherein the reference antibody comprises HCDR1 of SEQ ID NO: HCDR1B, HCDR2 of SEQ ID NO: 16 (HCDR2B), HCDR3 of SEQ ID NO: 32 (HCDR3B), LCDR1 of SEQ ID NO: 47 (LCDR1B), LCDR2 of SEQ ID NO: 59 (LCDR2B), and LCDR3 of SEQ ID NO: 70 (LCDR3B).

[0216] In some embodiments, the antibody or its antigen-binding fragment comprises HCDR1 of SEQ ID NO: 3 (HCDR1C), HCDR2 of SEQ ID NO: 17 (HCDR2C), and HCDR3 of SEQ ID NO: 33 (HCDR3C). In some embodiments, the antibody or its antigen-binding fragment comprises LCDR1 of SEQ ID NO: 47 (LCDR1B), LCDR2 of SEQ ID NO: 59 (LCDR2B), and LCDR3 of SEQ ID NO: 71 (LCDR3C). In some embodiments, the antibody or its antigen-binding fragment comprises HCDR1 of SEQ ID NO: 3 (HCDR1C), HCDR2 of SEQ ID NO: 17 (HCDR2C), HCDR3 of SEQ ID NO: 33 (HCDR3C), LCDR1 of SEQ ID NO: 47 (LCDR1B), LCDR2 of SEQ ID NO: 59 (LCDR2B), and LCDR3 of SEQ ID NO: 71 (LCDR3C).

[0217] In some embodiments, the antibody or its antigen-binding fragment competes with a reference antibody, wherein the reference antibody comprises HCDR1 of SEQ ID NO: 3 (HCDR1C), HCDR2 of SEQ ID NO: 17 (HCDR2C), HCDR3 of SEQ ID NO: 33 (HCDR3C), LCDR1 of SEQ ID NO: 47 (LCDR1B), LCDR2 of SEQ ID NO: 59 (LCDR2B), and LCDR3 of SEQ ID NO: 71 (LCDR3C).

[0218] In some embodiments, the antibody or its antigen-binding fragment comprises HCDR1 of SEQ ID NO: 4 (HCDR1D), HCDR2 of SEQ ID NO: 18 (HCDR2D), and HCDR3 of SEQ ID NO: 34 (HCDR3D). In some embodiments, the antibody or its antigen-binding fragment comprises LCDR1 of SEQ ID NO: 48 (LCDR1C), LCDR2 of SEQ ID NO: 60 (LCDR2C), and LCDR3 of SEQ ID NO: 72 (LCDR3D). In some embodiments, the antibody or its antigen-binding fragment comprises HCDR1 of SEQ ID NO: 4 (HCDR1D), HCDR2 of SEQ ID NO: 18 (HCDR2D), HCDR3 of SEQ ID NO: 34 (HCDR3D), LCDR1 of SEQ ID NO: 48 (LCDR1C), LCDR2 of SEQ ID NO: 60 (LCDR2C), and LCDR3 of SEQ ID NO: 72 (LCDR3D).

[0219] In some embodiments, the antibody or its antigen-binding fragment competes with a reference antibody, wherein the reference antibody comprises HCDR1 of SEQ ID NO: 4 (HCDR1D), HCDR2 of SEQ ID NO: 18 (HCDR2D), HCDR3 of SEQ ID NO: 34 (HCDR3D), LCDR1 of SEQ ID NO: 48 (LCDR1C), LCDR2 of SEQ ID NO: 60 (LCDR2C), and LCDR3 of SEQ ID NO: 72 (LCDR3D).

[0220] In some embodiments, the antibody or its antigen-binding fragment comprises HCDR1 of SEQ ID NO: 4 (HCDR1D), HCDR2 of SEQ ID NO: 19 (HCDR2E), and HCDR3 of SEQ ID NO: 35 (HCDR3E). In some embodiments, the antibody or its antigen-binding fragment comprises LCDR1 of SEQ ID NO: 48 (LCDR1C), LCDR2 of SEQ ID NO: 60 (LCDR2C), and LCDR3 of SEQ ID NO: 72 (LCDR3D). In some embodiments, the antibody or its antigen-binding fragment comprises HCDR1 of SEQ ID NO: 4 (HCDR1D), HCDR2 of SEQ ID NO: 19 (HCDR2E), HCDR3 of SEQ ID NO: 35 (HCDR3E), LCDR1 of SEQ ID NO: 48 (LCDR1C), LCDR2 of SEQ ID NO: 60 (LCDR2C), and LCDR3 of SEQ ID NO: 72 (LCDR3D).

[0221] In some embodiments, the antibody or its antigen-binding fragment competes with a reference antibody, wherein the reference antibody comprises HCDR1 of SEQ ID NO: 4 (HCDR1D), HCDR2 of SEQ ID NO: 19 (HCDR2E), HCDR3 of SEQ ID NO: 35 (HCDR3E), LCDR1 of SEQ ID NO: 48 (LCDR1C), LCDR2 of SEQ ID NO: 60 (LCDR2C), and LCDR3 of SEQ ID NO: 72 (LCDR3D).

[0222] In some embodiments, the antibody or its antigen-binding fragment comprises HCDR1 of SEQ ID NO: 5 (HCDR1E), HCDR2 of SEQ ID NO: 20 (HCDR2F), and HCDR3 of SEQ ID NO: 36 (HCDR3F). In some embodiments, the antibody or its antigen-binding fragment comprises LCDR1 of SEQ ID NO: 49 (LCDR1D), LCDR2 of SEQ ID NO: 61 (LCDR2D), and LCDR3 of SEQ ID NO: 73 (LCDR3E). In some embodiments, the antibody or its antigen-binding fragment comprises HCDR1 of SEQ ID NO: 5 (HCDR1E), HCDR2 of SEQ ID NO: 20 (HCDR2F), HCDR3 of SEQ ID NO: 36 (HCDR3F), LCDR1 of SEQ ID NO: 49 (LCDR1D), LCDR2 of SEQ ID NO: 61 (LCDR2D), and LCDR3 of SEQ ID NO: 73 (LCDR3E).

[0223] In some embodiments, the antibody or its antigen-binding fragment competes with a reference antibody, wherein the reference antibody comprises HCDR1 of SEQ ID NO: 5 (HCDR1E), HCDR2 of SEQ ID NO: 20 (HCDR2F), HCDR3 of SEQ ID NO: 36 (HCDR3F), LCDR1 of SEQ ID NO: 49 (LCDR1D), LCDR2 of SEQ ID NO: 61 (LCDR2D), and LCDR3 of SEQ ID NO: 73 (LCDR3E).

[0224] In some embodiments, the antibody or its antigen-binding fragment comprises HCDR1 of SEQ ID NO: 6 (HCDR1F), HCDR2 of SEQ ID NO: 21 (HCDR2G), and HCDR3 of SEQ ID NO: 37 (HCDR3G). In some embodiments, the antibody or its antigen-binding fragment comprises LCDR1 of SEQ ID NO: 50 (LCDR1E), LCDR2 of SEQ ID NO: 62 (LCDR2E), and LCDR3 of SEQ ID NO: 74 (LCDR3F). In some embodiments, the antibody or its antigen-binding fragment comprises HCDR1 of SEQ ID NO: 6 (HCDR1F), HCDR2 of SEQ ID NO: 21 (HCDR2G), HCDR3 of SEQ ID NO: 37 (HCDR3G), LCDR1 of SEQ ID NO: 50 (LCDR1E), LCDR2 of SEQ ID NO: 62 (LCDR2E), and LCDR3 of SEQ ID NO: 74 (LCDR3F).

[0225] In some embodiments, the antibody or its antigen-binding fragment competes with a reference antibody, wherein the reference antibody comprises HCDR1 of SEQ ID NO: 6 (HCDR1F), HCDR2 of SEQ ID NO: 21 (HCDR2G), HCDR3 of SEQ ID NO: 37 (HCDR3G), LCDR1 of SEQ ID NO: 50 (LCDR1E), LCDR2 of SEQ ID NO: 62 (LCDR2E), and LCDR3 of SEQ ID NO: 74 (LCDR3F).

[0226] In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a CDR differing from one or more amino acids in the CDRs shown in Table A. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a CDR differing from any of the CDRs shown in Table A by no more than 5 amino acids. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a CDR differing from any of the CDRs shown in Table A by no more than 4 amino acids. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a CDR differing from any of the CDRs shown in Table A by no more than 3 amino acids. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a CDR differing from any of the CDRs shown in Table A by no more than 2 amino acids. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a CDR differing from any of the CDRs shown in Table A by no more than 1 amino acid.

[0227] In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises: HCDR1 containing an amino acid sequence that differs from GYTFTGYY (SEQ ID NO: 1, HCDR1A) by no more than 2 amino acids; HCDR2 containing an amino acid sequence that differs from INPSGGT (SEQ ID NO: 15, HCDR2A) by no more than 1 amino acid; HCDR3 containing an amino acid sequence that differs from AREGANWDYYYYGMDV (SEQ ID NO: 31, HCDR3A) by no more than 4 amino acids; LCDR1 containing an amino acid sequence that differs from SSNIGSKT (SEQ ID NO: 46, LCDR1A) by no more than 2 amino acids; LCDR2 containing an amino acid sequence that differs from SNN (SEQ ID NO: 58, LCDR2A) by no more than 1 amino acid; and LCDR3 containing an amino acid sequence that differs from AAWDDSLNGPV (SEQ ID NO: 69, LCDR3A) by no more than 4 amino acids.

[0228] In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises: HCDR1 containing an amino acid sequence that differs from GFTFSSYT (SEQ ID NO: 2, HCDR1B) by no more than 2 amino acids; HCDR2 containing an amino acid sequence that differs from ISIVGNYI (SEQ ID NO: 16, HCDR2B) by no more than 1 amino acid; HCDR3 containing an amino acid sequence that differs from ARRKWEHDAFDI (SEQ ID NO: 32, HCDR3B) by no more than 4 amino acids; LCDR1 containing an amino acid sequence that differs from SLRSYY (SEQ ID NO: 47, LCDR1B) by no more than 2 amino acids; LCDR2 containing an amino acid sequence that differs from GKN (SEQ ID NO: 59, LCDR2B) by no more than 1 amino acid; and LCDR3 containing an amino acid sequence that differs from TSRDNSGNHVV (SEQ ID NO: 70, LCDR3B) by no more than 4 amino acids.

[0229] In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises: HCDR1 containing an amino acid sequence that differs from GFTFSSYS (SEQ ID NO: 3, HCDR1C) by no more than 2 amino acids; HCDR2 containing an amino acid sequence that differs from ISTSSSYI (SEQ ID NO: 17, HCDR2C) by no more than 1 amino acid; HCDR3 containing an amino acid sequence that differs from ARRAWESDAFAI (SEQ ID NO: 33, HCDR3C) by no more than 4 amino acids; LCDR1 containing an amino acid sequence that differs from SLRSYY (SEQ ID NO: 47, LCDR1B) by no more than 2 amino acids; LCDR2 containing an amino acid sequence that differs from GKN (SEQ ID NO: 59, LCDR2B) by no more than 1 amino acid; and LCDR3 containing an amino acid sequence that differs from NSRDSSGNHVV (SEQ ID NO: 71, LCDR3C) by no more than 4 amino acids.

[0230] In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises: HCDR1 containing an amino acid sequence that differs from GFTFSSYA (SEQ ID NO: 4, HCDR1D) by no more than 2 amino acids; HCDR2 containing an amino acid sequence that differs from IDSSGGIA (SEQ ID NO: 18, HCDR2D) by no more than 1 amino acid; HCDR3 containing an amino acid sequence that differs from VRDGY (SEQ ID NO: 34, HCDR3D) by no more than 4 amino acids; LCDR1 containing an amino acid sequence that differs from QSLLDSDD (SEQ ID NO: 48, LCDR1C) by no more than 2 amino acids; LCDR2 containing an amino acid sequence that differs from TLS (SEQ ID NO: 60, LCDR2C) by no more than 1 amino acid; and LCDR3 containing an amino acid sequence that differs from MQRIEFPLT (SEQ ID NO: 72, LCDR3D) by no more than 4 amino acids.

[0231] In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises: HCDR1 containing an amino acid sequence that differs from GFTFSSYA (SEQ ID NO: 4, HCDR1D) by no more than 2 amino acids; HCDR2 containing an amino acid sequence that differs from IHYSGGTT (SEQ ID NO: 19, HCDR2E) by no more than 1 amino acid; HCDR3 containing an amino acid sequence that differs from VKDGY (SEQ ID NO: 35, HCDR3E) by no more than 4 amino acids; LCDR1 containing an amino acid sequence that differs from QSLLDSDDGYTY (SEQ ID NO: 48, LCDR1C) by no more than 2 amino acids; LCDR2 containing an amino acid sequence that differs from TLS (SEQ ID NO: 60, LCDR2C) by no more than 1 amino acid; and LCDR3 containing an amino acid sequence that differs from MQRIEFPLT (SEQ ID NO: 72, LCDR3D) by no more than 4 amino acids.

[0232] In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises: HCDR1 containing an amino acid sequence that differs from GFTFSRFW (SEQ ID NO: 5, HCDR1E) by no more than 2 amino acids; HCDR2 containing an amino acid sequence that differs from TKQDGSEK (SEQ ID NO: 20, HCDR2F) by no more than 1 amino acid; HCDR3 containing an amino acid sequence that differs from AREGSGAYWAFDI (SEQ ID NO: 36, HCDR3F) by no more than 4 amino acids; LCDR1 containing an amino acid sequence that differs from QSLVHNDGNTY (SEQ ID NO: 49, LCDR1D) by no more than 2 amino acids; LCDR2 containing an amino acid sequence that differs from KIS (SEQ ID NO: 61, LCDR2D) by no more than 1 amino acid; and LCDR3 containing an amino acid sequence that differs from LQATQFPLT (SEQ ID NO: 73, LCDR3E) by no more than 4 amino acids.

[0233] In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises: HCDR1 containing an amino acid sequence that differs from GGSISSYY (SEQ ID NO: 6, HCDR1F) by no more than 2 amino acids; HCDR2 containing an amino acid sequence that differs from IYTRGST (SEQ ID NO: 21, HCDR2G) by no more than 1 amino acid; HCDR3 containing an amino acid sequence that differs from ARVFGGNYRFDAFHI (SEQ ID NO: 37, HCDR3G) by no more than 4 amino acids; LCDR1 containing an amino acid sequence that differs from SSNIGAGYD (SEQ ID NO: 50, LCDR1E) by no more than 2 amino acids; LCDR2 containing an amino acid sequence that differs from GNN (SEQ ID NO: 62, LCDR2E) by no more than 1 amino acid; and LCDR3 containing an amino acid sequence that differs from QSYDSSLSGYV (SEQ ID NO: 74, LCDR3F) by no more than 4 amino acids.

[0234] Table B. Exemplary VH and VL sequences of human anti-α7β1 integrin antibodies .

[0235]

[0236] In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH1) containing at least 80% of the same amino acid sequence as SEQ ID NO: 128. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH1) containing at least 83% of the same amino acid sequence as SEQ ID NO: 128. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH1) containing at least 85% of the same amino acid sequence as SEQ ID NO: 128. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH1) containing at least 87% of the same amino acid sequence as SEQ ID NO: 128. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH1) containing at least 90% of the same amino acid sequence as SEQ ID NO: 128. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH1) containing at least 92% of the same amino acid sequence as SEQ ID NO: 128. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH1) containing at least 93% of the same amino acid sequence as SEQ ID NO: 128. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH1) containing at least 94% of the same amino acid sequence as SEQ ID NO: 128. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH1) containing at least 95% of the same amino acid sequence as SEQ ID NO: 128. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH1) containing at least 97% of the same amino acid sequence as SEQ ID NO: 128. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH1) containing at least 98% of the same amino acid sequence as SEQ ID NO: 128. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH1) containing at least 99% of the same amino acid sequence as SEQ ID NO: 128. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH1) containing the same amino acid sequence as SEQ ID NO: 128.

[0237] In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH2) containing at least 80% of the same amino acid sequence as SEQ ID NO: 130. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH2) containing at least 83% of the same amino acid sequence as SEQ ID NO: 130. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH2) containing at least 85% of the same amino acid sequence as SEQ ID NO: 130. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH2) containing at least 87% of the same amino acid sequence as SEQ ID NO: 130. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH2) containing at least 90% of the same amino acid sequence as SEQ ID NO: 130. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH2) containing at least 92% of the same amino acid sequence as SEQ ID NO: 130. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH2) containing at least 93% of the same amino acid sequence as SEQ ID NO: 130. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH2) containing at least 94% of the same amino acid sequence as SEQ ID NO: 130. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH2) containing at least 95% of the same amino acid sequence as SEQ ID NO: 130. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH2) containing at least 97% of the same amino acid sequence as SEQ ID NO: 130. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH2) containing at least 98% of the same amino acid sequence as SEQ ID NO: 130. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH2) containing at least 99% of the same amino acid sequence as SEQ ID NO: 130. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH2) containing the same amino acid sequence as SEQ ID NO: 130.

[0238] In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH3) containing at least 80% of the same amino acid sequence as SEQ ID NO: 132. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH3) containing at least 83% of the same amino acid sequence as SEQ ID NO: 132. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH3) containing at least 85% of the same amino acid sequence as SEQ ID NO: 132. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH3) containing at least 87% of the same amino acid sequence as SEQ ID NO: 132. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH3) containing at least 90% of the same amino acid sequence as SEQ ID NO: 132. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH3) containing at least 92% of the same amino acid sequence as SEQ ID NO: 132. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH3) containing at least 93% of the same amino acid sequence as SEQ ID NO: 132. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH3) containing at least 94% of the same amino acid sequence as SEQ ID NO: 132. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH3) containing at least 95% of the same amino acid sequence as SEQ ID NO: 132. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH3) containing at least 97% of the same amino acid sequence as SEQ ID NO: 132. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH3) containing at least 98% of the same amino acid sequence as SEQ ID NO: 132. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH3) containing at least 99% of the same amino acid sequence as SEQ ID NO: 132. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH3) containing the same amino acid sequence as SEQ ID NO: 132.

[0239] In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH4) containing at least 80% of the same amino acid sequence as SEQ ID NO: 134. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH4) containing at least 83% of the same amino acid sequence as SEQ ID NO: 134. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH4) containing at least 85% of the same amino acid sequence as SEQ ID NO: 134. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH4) containing at least 87% of the same amino acid sequence as SEQ ID NO: 134. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH4) containing at least 90% of the same amino acid sequence as SEQ ID NO: 134. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH4) containing at least 92% of the same amino acid sequence as SEQ ID NO: 134. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH4) containing at least 93% of the same amino acid sequence as SEQ ID NO: 134. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH4) containing at least 94% of the same amino acid sequence as SEQ ID NO: 134. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH4) containing at least 95% of the same amino acid sequence as SEQ ID NO: 134. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH4) containing at least 97% of the same amino acid sequence as SEQ ID NO: 134. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH4) containing at least 98% of the same amino acid sequence as SEQ ID NO: 134. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH4) containing at least 99% of the same amino acid sequence as SEQ ID NO: 134. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH4) containing the same amino acid sequence as SEQ ID NO: 134.

[0240] In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH5) containing at least 80% of the same amino acid sequence as SEQ ID NO: 136. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH5) containing at least 83% of the same amino acid sequence as SEQ ID NO: 136. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH5) containing at least 85% of the same amino acid sequence as SEQ ID NO: 136. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH5) containing at least 87% of the same amino acid sequence as SEQ ID NO: 136. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH5) containing at least 90% of the same amino acid sequence as SEQ ID NO: 136. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH5) containing at least 92% of the same amino acid sequence as SEQ ID NO: 136. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH5) containing at least 93% of the same amino acid sequence as SEQ ID NO: 136. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH5) containing at least 94% of the same amino acid sequence as SEQ ID NO: 136. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH5) containing at least 95% of the same amino acid sequence as SEQ ID NO: 136. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH5) containing at least 97% of the same amino acid sequence as SEQ ID NO: 136. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH5) containing at least 98% of the same amino acid sequence as SEQ ID NO: 136. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH5) containing at least 99% of the same amino acid sequence as SEQ ID NO: 136. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH5) containing the same amino acid sequence as SEQ ID NO: 136.

[0241] In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH6) containing at least 80% of the same amino acid sequence as SEQ ID NO: 138. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH6) containing at least 83% of the same amino acid sequence as SEQ ID NO: 138. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH6) containing at least 85% of the same amino acid sequence as SEQ ID NO: 138. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH6) containing at least 87% of the same amino acid sequence as SEQ ID NO: 138. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH6) containing at least 90% of the same amino acid sequence as SEQ ID NO: 138. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH6) containing at least 92% of the same amino acid sequence as SEQ ID NO: 138. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH6) containing at least 93% of the same amino acid sequence as SEQ ID NO: 138. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH6) containing at least 94% of the same amino acid sequence as SEQ ID NO: 138. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH6) containing at least 95% of the same amino acid sequence as SEQ ID NO: 138. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH6) containing at least 97% of the same amino acid sequence as SEQ ID NO: 138. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH6) containing at least 98% of the same amino acid sequence as SEQ ID NO: 138. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH6) containing at least 99% of the same amino acid sequence as SEQ ID NO: 138. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH6) containing the same amino acid sequence as SEQ ID NO: 138.

[0242] In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH7) containing at least 80% of the same amino acid sequence as SEQ ID NO: 140. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH7) containing at least 83% of the same amino acid sequence as SEQ ID NO: 140. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH7) containing at least 85% of the same amino acid sequence as SEQ ID NO: 140. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH7) containing at least 87% of the same amino acid sequence as SEQ ID NO: 140. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH7) containing at least 90% of the same amino acid sequence as SEQ ID NO: 140. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH7) containing at least 92% of the same amino acid sequence as SEQ ID NO: 140. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH7) containing at least 93% of the same amino acid sequence as SEQ ID NO: 140. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH7) containing at least 94% of the same amino acid sequence as SEQ ID NO: 140. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH7) containing at least 95% of the same amino acid sequence as SEQ ID NO: 140. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH7) containing at least 97% of the same amino acid sequence as SEQ ID NO: 140. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH7) containing at least 98% of the same amino acid sequence as SEQ ID NO: 140. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH7) containing at least 99% of the same amino acid sequence as SEQ ID NO: 140. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH7) containing the same amino acid sequence as SEQ ID NO: 140.

[0243] In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL1) containing at least 80% of the same amino acid sequence as SEQ ID NO: 129. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL1) containing at least 83% of the same amino acid sequence as SEQ ID NO: 129. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL1) containing at least 85% of the same amino acid sequence as SEQ ID NO: 129. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL1) containing at least 87% of the same amino acid sequence as SEQ ID NO: 129. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL1) containing at least 90% of the same amino acid sequence as SEQ ID NO: 129. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL1) containing at least 92% of the same amino acid sequence as SEQ ID NO: 129. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL1) containing at least 93% of the same amino acid sequence as SEQ ID NO: 129. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL1) containing at least 94% of the same amino acid sequence as SEQ ID NO: 129. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL1) containing at least 95% of the same amino acid sequence as SEQ ID NO: 129. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL1) containing at least 97% of the same amino acid sequence as SEQ ID NO: 129. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL1) containing at least 98% of the same amino acid sequence as SEQ ID NO: 129. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL1) containing at least 99% of the same amino acid sequence as SEQ ID NO: 129. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL1) containing the same amino acid sequence as SEQ ID NO: 129.

[0244] In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL2) containing at least 80% of the same amino acid sequence as SEQ ID NO: 131. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL2) containing at least 83% of the same amino acid sequence as SEQ ID NO: 131. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL2) containing at least 85% of the same amino acid sequence as SEQ ID NO: 131. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL2) containing at least 87% of the same amino acid sequence as SEQ ID NO: 131. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL2) containing at least 90% of the same amino acid sequence as SEQ ID NO: 131. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL2) containing at least 92% of the same amino acid sequence as SEQ ID NO: 131. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL2) containing at least 93% of the same amino acid sequence as SEQ ID NO: 131. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL2) containing at least 94% of the same amino acid sequence as SEQ ID NO: 131. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL2) containing at least 95% of the same amino acid sequence as SEQ ID NO: 131. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL2) containing at least 97% of the same amino acid sequence as SEQ ID NO: 131. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL2) containing at least 98% of the same amino acid sequence as SEQ ID NO: 131. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL2) containing at least 99% of the same amino acid sequence as SEQ ID NO: 131. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL2) containing the same amino acid sequence as SEQ ID NO: 131.

[0245] In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL3) containing at least 80% of the same amino acid sequence as SEQ ID NO: 133. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL3) containing at least 83% of the same amino acid sequence as SEQ ID NO: 133. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL3) containing at least 85% of the same amino acid sequence as SEQ ID NO: 133. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL3) containing at least 87% of the same amino acid sequence as SEQ ID NO: 133. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL3) containing at least 90% of the same amino acid sequence as SEQ ID NO: 133. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL3) containing at least 92% of the same amino acid sequence as SEQ ID NO: 133. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL3) containing at least 93% of the same amino acid sequence as SEQ ID NO: 133. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL3) containing at least 94% of the same amino acid sequence as SEQ ID NO: 133. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL3) containing at least 95% of the same amino acid sequence as SEQ ID NO: 133. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL3) containing at least 97% of the same amino acid sequence as SEQ ID NO: 133. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL3) containing at least 98% of the same amino acid sequence as SEQ ID NO: 133. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL3) containing at least 99% of the same amino acid sequence as SEQ ID NO: 133. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL3) containing the same amino acid sequence as SEQ ID NO: 133.

[0246] In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL4) containing at least 80% of the same amino acid sequence as SEQ ID NO: 135. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL4) containing at least 83% of the same amino acid sequence as SEQ ID NO: 135. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL4) containing at least 85% of the same amino acid sequence as SEQ ID NO: 135. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL4) containing at least 87% of the same amino acid sequence as SEQ ID NO: 135. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL4) containing at least 90% of the same amino acid sequence as SEQ ID NO: 135. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL4) containing at least 92% of the same amino acid sequence as SEQ ID NO: 135. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL4) containing at least 93% of the same amino acid sequence as SEQ ID NO: 135. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL4) containing at least 94% of the same amino acid sequence as SEQ ID NO: 135. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL4) containing at least 95% of the same amino acid sequence as SEQ ID NO: 135. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL4) containing at least 97% of the same amino acid sequence as SEQ ID NO: 135. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL4) containing at least 98% of the same amino acid sequence as SEQ ID NO: 135. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL4) containing at least 99% of the same amino acid sequence as SEQ ID NO: 135. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL4) containing the same amino acid sequence as SEQ ID NO: 135.

[0247] In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL5) containing at least 80% of the same amino acid sequence as SEQ ID NO: 137. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL5) containing at least 83% of the same amino acid sequence as SEQ ID NO: 137. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL5) containing at least 85% of the same amino acid sequence as SEQ ID NO: 137. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL5) containing at least 87% of the same amino acid sequence as SEQ ID NO: 137. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL5) containing at least 90% of the same amino acid sequence as SEQ ID NO: 137. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL5) containing at least 92% of the same amino acid sequence as SEQ ID NO: 137. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL5) containing at least 93% of the same amino acid sequence as SEQ ID NO: 137. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL5) containing at least 94% of the same amino acid sequence as SEQ ID NO: 137. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL5) containing at least 95% of the same amino acid sequence as SEQ ID NO: 137. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL5) containing at least 97% of the same amino acid sequence as SEQ ID NO: 137. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL5) containing at least 98% of the same amino acid sequence as SEQ ID NO: 137. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL5) containing at least 99% of the same amino acid sequence as SEQ ID NO: 137. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL5) containing the same amino acid sequence as SEQ ID NO: 137.

[0248] In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL6) containing at least 80% of the same amino acid sequence as SEQ ID NO: 139. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL6) containing at least 83% of the same amino acid sequence as SEQ ID NO: 139. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL6) containing at least 85% of the same amino acid sequence as SEQ ID NO: 139. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL6) containing at least 87% of the same amino acid sequence as SEQ ID NO: 139. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL6) containing at least 90% of the same amino acid sequence as SEQ ID NO: 139. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL6) containing at least 92% of the same amino acid sequence as SEQ ID NO: 139. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL6) containing at least 93% of the same amino acid sequence as SEQ ID NO: 139. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL6) containing at least 94% of the same amino acid sequence as SEQ ID NO: 139. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL6) containing at least 95% of the same amino acid sequence as SEQ ID NO: 139. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL6) containing at least 97% of the same amino acid sequence as SEQ ID NO: 139. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL6) containing at least 98% of the same amino acid sequence as SEQ ID NO: 139. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL6) containing at least 99% of the same amino acid sequence as SEQ ID NO: 139. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL6) containing the same amino acid sequence as SEQ ID NO: 139.

[0249] In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL7) containing at least 80% of the same amino acid sequence as SEQ ID NO: 141. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL7) containing at least 83% of the same amino acid sequence as SEQ ID NO: 141. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL7) containing at least 85% of the same amino acid sequence as SEQ ID NO: 141. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL7) containing at least 87% of the same amino acid sequence as SEQ ID NO: 141. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL7) containing at least 90% of the same amino acid sequence as SEQ ID NO: 141. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL7) containing at least 92% of the same amino acid sequence as SEQ ID NO: 141. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL7) containing at least 93% of the same amino acid sequence as SEQ ID NO: 141. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL7) containing at least 94% of the same amino acid sequence as SEQ ID NO: 141. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL7) containing at least 95% of the same amino acid sequence as SEQ ID NO: 141. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL7) containing at least 97% of the same amino acid sequence as SEQ ID NO: 141. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL7) containing at least 98% of the same amino acid sequence as SEQ ID NO: 141. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL7) containing at least 99% of the same amino acid sequence as SEQ ID NO: 141. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL7) containing the same amino acid sequence as SEQ ID NO: 141.

[0250] In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a heavy variable region (VH1) containing the amino acid sequence of SEQ ID NO: 128 and a light variable region (VL1) containing the amino acid sequence of SEQ ID NO: 129.

[0251] In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a heavy variable region (VH2) containing the amino acid sequence of SEQ ID NO: 130 and a light variable region containing the amino acid sequence of SEQ ID NO: VL2.

[0252] In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a heavy variable region (VH3) containing the amino acid sequence of SEQ ID NO: 132 and a light variable region (VL3) containing the amino acid sequence of SEQ ID NO: 133.

[0253] In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a heavy variable region (VH4) containing the amino acid sequence of SEQ ID NO: 134 and a light variable region (VL4) containing the amino acid sequence of SEQ ID NO: 135.

[0254] In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a heavy variable region (VH5) containing the amino acid sequence of SEQ ID NO: 136 and a light variable region (VL5) containing the amino acid sequence of SEQ ID NO: 137.

[0255] In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a heavy variable region (VH6) containing the amino acid sequence of SEQ ID NO: 138 and a light variable region (VL6) containing the amino acid sequence of SEQ ID NO: 139.

[0256] In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a heavy variable region (VH7) containing the amino acid sequence of SEQ ID NO: 140 and a light variable region (VL7) containing the amino acid sequence of SEQ ID NO: 141.

[0257] Table H. Exemplary heavy and light chain sequences of human anti-α7β1 integrin antibodies. .

[0258]

[0259] In some embodiments, the integrin α7β1 antibody comprises a heavy chain containing at least 80% of the same amino acid sequence as SEQ ID NO: 118. In some embodiments, the integrin α7β1 antibody comprises a heavy chain containing at least 83% of the same amino acid sequence as SEQ ID NO: 118. In some embodiments, the integrin α7β1 antibody comprises a heavy chain containing at least 85% of the same amino acid sequence as SEQ ID NO: 118. In some embodiments, the integrin α7β1 antibody comprises a heavy chain containing at least 87% of the same amino acid sequence as SEQ ID NO: 118. In some embodiments, the integrin α7β1 antibody comprises a heavy chain containing at least 90% of the same amino acid sequence as SEQ ID NO: 118. In some embodiments, the integrin α7β1 antibody comprises a heavy chain containing at least 92% of the same amino acid sequence as SEQ ID NO: 118. In some embodiments, the integrin α7β1 antibody comprises a heavy chain containing at least 93% of the same amino acid sequence as SEQ ID NO: 118. In some embodiments, the integrin α7β1 antibody comprises a heavy chain containing at least 94% of the same amino acid sequence as SEQ ID NO: 118. In some embodiments, the integrin α7β1 antibody comprises a heavy chain containing at least 95% of the same amino acid sequence as SEQ ID NO: 118. In some embodiments, the integrin α7β1 antibody comprises a heavy chain containing at least 97% of the same amino acid sequence as SEQ ID NO: 118. In some embodiments, the integrin α7β1 antibody comprises a heavy chain containing at least 98% of the same amino acid sequence as SEQ ID NO: 118. In some embodiments, the integrin α7β1 antibody comprises a heavy chain containing at least 99% of the same amino acid sequence as SEQ ID NO: 118. In some embodiments, the integrin α7β1 antibody comprises a heavy chain containing the same amino acid sequence as SEQ ID NO: 118.

[0260] In some embodiments, the integrin α7β1 antibody comprises a heavy chain containing at least 80% of the same amino acid sequence as SEQ ID NO: 120. In some embodiments, the integrin α7β1 antibody comprises a heavy chain containing at least 83% of the same amino acid sequence as SEQ ID NO: 120. In some embodiments, the integrin α7β1 antibody comprises a heavy chain containing at least 85% of the same amino acid sequence as SEQ ID NO: 120. In some embodiments, the integrin α7β1 antibody comprises a heavy chain containing at least 87% of the same amino acid sequence as SEQ ID NO: 120. In some embodiments, the integrin α7β1 antibody comprises a heavy chain containing at least 90% of the same amino acid sequence as SEQ ID NO: 120. In some embodiments, the integrin α7β1 antibody comprises a heavy chain containing at least 92% of the same amino acid sequence as SEQ ID NO: 120. In some embodiments, the integrin α7β1 antibody comprises a heavy chain containing at least 93% of the same amino acid sequence as SEQ ID NO: 120. In some embodiments, the integrin α7β1 antibody comprises a heavy chain containing at least 94% of the same amino acid sequence as SEQ ID NO: 120. In some embodiments, the integrin α7β1 antibody comprises a heavy chain containing at least 95% of the same amino acid sequence as SEQ ID NO: 120. In some embodiments, the integrin α7β1 antibody comprises a heavy chain containing at least 97% of the same amino acid sequence as SEQ ID NO: 120. In some embodiments, the integrin α7β1 antibody comprises a heavy chain containing at least 98% of the same amino acid sequence as SEQ ID NO: 120. In some embodiments, the integrin α7β1 antibody comprises a heavy chain containing at least 99% of the same amino acid sequence as SEQ ID NO: 120. In some embodiments, the integrin α7β1 antibody comprises a heavy chain containing the same amino acid sequence as SEQ ID NO: 120.

[0261] In some embodiments, the integrin α7β1 antibody comprises a light chain containing at least 80% of the same amino acid sequence as SEQ ID NO: 119. In some embodiments, the integrin α7β1 antibody comprises a light chain containing at least 83% of the same amino acid sequence as SEQ ID NO: 119. In some embodiments, the integrin α7β1 antibody comprises a light chain containing at least 85% of the same amino acid sequence as SEQ ID NO: 119. In some embodiments, the integrin α7β1 antibody comprises a light chain containing at least 87% of the same amino acid sequence as SEQ ID NO: 119. In some embodiments, the integrin α7β1 antibody comprises a light chain containing at least 90% of the same amino acid sequence as SEQ ID NO: 119. In some embodiments, the integrin α7β1 antibody comprises a light chain containing at least 92% of the same amino acid sequence as SEQ ID NO: 119. In some embodiments, the integrin α7β1 antibody comprises a light chain containing at least 93% of the same amino acid sequence as SEQ ID NO: 119. In some embodiments, the integrin α7β1 antibody comprises a light chain containing at least 94% of the same amino acid sequence as SEQ ID NO: 119. In some embodiments, the integrin α7β1 antibody comprises a light chain containing at least 95% of the same amino acid sequence as SEQ ID NO: 119. In some embodiments, the integrin α7β1 antibody comprises a light chain containing at least 97% of the same amino acid sequence as SEQ ID NO: 119. In some embodiments, the integrin α7β1 antibody comprises a light chain containing at least 98% of the same amino acid sequence as SEQ ID NO: 119. In some embodiments, the integrin α7β1 antibody comprises a light chain containing at least 99% of the same amino acid sequence as SEQ ID NO: 119. In some embodiments, the integrin α7β1 antibody comprises a light chain containing the same amino acid sequence as SEQ ID NO: 119.

[0262] In some embodiments, the integrin α7β1 antibody comprises a light chain containing at least 80% of the same amino acid sequence as SEQ ID NO: 121. In some embodiments, the integrin α7β1 antibody comprises a light chain containing at least 83% of the same amino acid sequence as SEQ ID NO: 121. In some embodiments, the integrin α7β1 antibody comprises a light chain containing at least 85% of the same amino acid sequence as SEQ ID NO: 121. In some embodiments, the integrin α7β1 antibody comprises a light chain containing at least 87% of the same amino acid sequence as SEQ ID NO: 121. In some embodiments, the integrin α7β1 antibody comprises a light chain containing at least 90% of the same amino acid sequence as SEQ ID NO: 121. In some embodiments, the integrin α7β1 antibody comprises a light chain containing at least 92% of the same amino acid sequence as SEQ ID NO: 121. In some embodiments, the integrin α7β1 antibody comprises a light chain containing at least 93% of the same amino acid sequence as SEQ ID NO: 121. In some embodiments, the integrin α7β1 antibody comprises a light chain containing at least 94% of the same amino acid sequence as SEQ ID NO: 121. In some embodiments, the integrin α7β1 antibody comprises a light chain containing at least 95% of the same amino acid sequence as SEQ ID NO: 121. In some embodiments, the integrin α7β1 antibody comprises a light chain containing at least 97% of the same amino acid sequence as SEQ ID NO: 121. In some embodiments, the integrin α7β1 antibody comprises a light chain containing at least 98% of the same amino acid sequence as SEQ ID NO: 121. In some embodiments, the integrin α7β1 antibody comprises a light chain containing at least 99% of the same amino acid sequence as SEQ ID NO: 121. In some embodiments, the integrin α7β1 antibody comprises a light chain containing the same amino acid sequence as SEQ ID NO: 121.

[0263] In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a heavy chain containing the amino acid sequence of SEQ ID NO: 118 and a light chain containing the amino acid sequence of SEQ ID NO: 119.

[0264] In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a heavy chain containing the amino acid sequence of SEQ ID NO: 120 and a light chain containing the amino acid sequence of SEQ ID NO: 121.

[0265] Anti-mouse α7β1 antibody

[0266] In some embodiments, the antibody or its antigen-binding fragment is an anti-mouse α7β1 antibody. In some embodiments, the antibody or its antigen-binding fragment comprises a CDR selected from Table C.

[0267] Table C. Exemplary CDRs for mouse anti-α7β1 antibodies .

[0268]

[0269]

[0270] In some embodiments, the antibody or its antigen-binding fragment comprises HCDR1 of SEQ ID NO: 7 (HCDR1G), HCDR2 of SEQ ID NO: 22 (HCDR2H), and HCDR3 of SEQ ID NO: 38 (HCDR3H). In some embodiments, the antibody or its antigen-binding fragment comprises LCDR1 of SEQ ID NO: 51 (LCDR1F), LCDR2 of SEQ ID NO: 63 (LCDR2F), and LCDR3 of SEQ ID NO: 75 (LCDR3G).

[0271] In some embodiments, the antibody or its antigen-binding fragment competes with a reference antibody, wherein the reference antibody comprises HCDR1 of SEQ ID NO: 7 (HCDR1G), HCDR2 of SEQ ID NO: 22 (HCDR2H), HCDR3 of SEQ ID NO: 38 (HCDR3H), LCDR1 of SEQ ID NO: 51 (LCDR1F), LCDR2 of SEQ ID NO: 63 (LCDR2F), and LCDR3 of SEQ ID NO: 75 (LCDR3G).

[0272] In some embodiments, the antibody or its antigen-binding fragment comprises HCDR1 of SEQ ID NO: 8 (HCDR1H), HCDR2 of SEQ ID NO: 23 (HCDR2I), and HCDR3 of SEQ ID NO: 39 (HCDR3I). In some embodiments, the antibody or its antigen-binding fragment comprises LCDR1 of SEQ ID NO: 52 (LCDR1G), LCDR2 of SEQ ID NO: 64 (LCDR2G), and LCDR3 of SEQ ID NO: 76 (LCDR3H).

[0273] In some embodiments, the antibody or its antigen-binding fragment competes with a reference antibody, wherein the reference antibody comprises HCDR1 of SEQ ID NO: 8 (HCDR1H), HCDR2 of SEQ ID NO: 23 (HCDR2I), HCDR3 of SEQ ID NO: 39 (HCDR3I), LCDR1 of SEQ ID NO: 52 (LCDR1G), LCDR2 of SEQ ID NO: 64 (LCDR2G), and LCDR3 of SEQ ID NO: 76 (LCDR3H).

[0274] In some embodiments, the antibody or its antigen-binding fragment comprises HCDR1 of SEQ ID NO: 9 (HCDR1I), HCDR2 of SEQ ID NO: 24 (HCDR2J), and HCDR3 of SEQ ID NO: 40 (HCDR3J). In some embodiments, the antibody or its antigen-binding fragment comprises LCDR1 of SEQ ID NO: 53 (LCDR1H), LCDR2 of SEQ ID NO: 65 (LCDR2H), and LCDR3 of SEQ ID NO: 77 (LCDR3I).

[0275] In some embodiments, the antibody or its antigen-binding fragment competes with a reference antibody, wherein the reference antibody comprises HCDR1 of SEQ ID NO: 9 (HCDR1I), HCDR2 of SEQ ID NO: 24 (HCDR2J), HCDR3 of SEQ ID NO: 40 (HCDR3J), LCDR1 of SEQ ID NO: 53 (LCDR1H), LCDR2 of SEQ ID NO: 65 (LCDR2H), and LCDR3 of SEQ ID NO: 77 (LCDR3I).

[0276] In some embodiments, the antibody or its antigen-binding fragment comprises HCDR1 of SEQ ID NO: 9 (HCDR1I), HCDR2 of SEQ ID NO: 25 (HCDR2K), and HCDR3 of SEQ ID NO: 40 (HCDR3J). In some embodiments, the antibody or its antigen-binding fragment comprises LCDR1 of SEQ ID NO: 54 (LCDR1I), LCDR2 of SEQ ID NO: 65 (LCDR2H), and LCDR3 of SEQ ID NO: LCDR3I.

[0277] In some embodiments, the antibody or its antigen-binding fragment competes with a reference antibody, wherein the reference antibody comprises HCDR1 of SEQ ID NO: 9 (HCDR1I), HCDR2 of SEQ ID NO: 25 (HCDR2K), HCDR3 of SEQ ID NO: 40 (HCDR3J), LCDR1 of SEQ ID NO: 54 (LCDR1I), LCDR2 of SEQ ID NO: 65 (LCDR2H), and LCDR3 of SEQ ID NO: 77 (LCDR3I).

[0278] In some embodiments, the antibody or its antigen-binding fragment comprises HCDR1 of SEQ ID NO: 9 (HCDR1I), HCDR2 of SEQ ID NO: 25 (HCDR2K), and HCDR3 of SEQ ID NO: 41 (HCDR3K). In some embodiments, the antibody or its antigen-binding fragment comprises LCDR1 of SEQ ID NO: 54 (LCDR1I), LCDR2 of SEQ ID NO: 65 (LCDR2H), and LCDR3 of SEQ ID NO: 78 (LCDR3J).

[0279] In some embodiments, the antibody or its antigen-binding fragment competes with a reference antibody, wherein the reference antibody comprises HCDR1 of SEQ ID NO: 9 (HCDR1I), HCDR2 of SEQ ID NO: 25 (HCDR2K), HCDR3 of SEQ ID NO: 41 (HCDR3K), LCDR1 of SEQ ID NO: 54 (LCDR1I), LCDR2 of SEQ ID NO: 65 (LCDR2H), and LCDR3 of SEQ ID NO: 78 (LCDR3J).

[0280] In some embodiments, the antibody or its antigen-binding fragment comprises HCDR1 of SEQ ID NO: 10 (HCDR1J), HCDR2 of SEQ ID NO: HCDR2L, and HCDR3 of SEQ ID NO: 42 (HCDR3L). In some embodiments, the antibody or its antigen-binding fragment comprises LCDR1 of SEQ ID NO: 55 (LCDR1J), LCDR2 of SEQ ID NO: 66 (LCDR2I), and LCDR3 of SEQ ID NO: 79 (LCDR3K).

[0281] In some embodiments, the antibody or its antigen-binding fragment competes with a reference antibody, wherein the reference antibody comprises HCDR1 of SEQ ID NO: 10 (HCDR1J), HCDR2 of SEQ ID NO: 26 (HCDR2L), HCDR3 of SEQ ID NO: 42 (HCDR3L), LCDR1 of SEQ ID NO: 55 (LCDR1J), LCDR2 of SEQ ID NO: 66 (LCDR2I), and LCDR3 of SEQ ID NO: 79 (LCDR3K).

[0282] In some embodiments, the antibody or its antigen-binding fragment comprises HCDR1 of SEQ ID NO: 11 (HCDR1K), HCDR2 of SEQ ID NO: 27 (HCDR2M), and HCDR3 of SEQ ID NO: 42 (HCDR3L). In some embodiments, the antibody or its antigen-binding fragment comprises LCDR1 of SEQ ID NO: 56 (LCDR1K), LCDR2 of SEQ ID NO: 66 (LCDR2I), and LCDR3 of SEQ ID NO: 80, LCDR3L.

[0283] In some embodiments, the antibody or its antigen-binding fragment competes with a reference antibody, wherein the reference antibody comprises HCDR1 of SEQ ID NO: 11 (HCDR1K), HCDR2 of SEQ ID NO: 27 (HCDR2M), HCDR3 of SEQ ID NO: 42 (HCDR3L), LCDR1 of SEQ ID NO: 56 (LCDR1K), LCDR2 of SEQ ID NO: 66 (LCDR2I), and LCDR3 of SEQ ID NO: 80 (LCDR3L).

[0284] In some embodiments, the antibody or its antigen-binding fragment comprises HCDR1 of SEQ ID NO: 11 (HCDR1K), HCDR2 of SEQ ID NO: 27 (HCDR2M), and HCDR3 of SEQ ID NO: 42 (HCDR3L). In some embodiments, the antibody or its antigen-binding fragment comprises LCDR1 of SEQ ID NO: 56 (LCDR1K), LCDR2 of SEQ ID NO: 67 (LCDR2J), and LCDR3 of SEQ ID NO: 80 (LCDR3L).

[0285] In some embodiments, the antibody or its antigen-binding fragment competes with a reference antibody, wherein the reference antibody comprises HCDR1 of SEQ ID NO: 11 (HCDR1K), HCDR2 of SEQ ID NO: 27 (HCDR2M), HCDR3 of SEQ ID NO: 42 (HCDR3L), LCDR1 of SEQ ID NO: 56 (LCDR1K), LCDR2 of SEQ ID NO: 67 (LCDR2J), and LCDR3 of SEQ ID NO: 80 (LCDR3L).

[0286] In some embodiments, the antibody or its antigen-binding fragment comprises HCDR1 of SEQ ID NO: 11 (HCDR1K), HCDR2 of SEQ ID NO: 27 (HCDR2M), and HCDR3 of SEQ ID NO: 43 (HCDR3M). In some embodiments, the antibody or its antigen-binding fragment comprises LCDR1 of SEQ ID NO: 56 (LCDR1K), LCDR2 of SEQ ID NO: 66 (LCDR2I), and LCDR3 of SEQ ID NO: 80 (LCDR3L).

[0287] In some embodiments, the antibody or its antigen-binding fragment competes with a reference antibody, wherein the reference antibody comprises HCDR1 of SEQ ID NO: 11 (HCDR1K), HCDR2 of SEQ ID NO: 27 (HCDR2M), HCDR3 of SEQ ID NO: 43 (HCDR3M), LCDR1 of SEQ ID NO: 56 (LCDR1K), LCDR2 of SEQ ID NO: 66 (LCDR2I), and LCDR3 of SEQ ID NO: 80 (LCDR3L).

[0288] In some embodiments, the antibody or its antigen-binding fragment comprises HCDR1 of SEQ ID NO: 10 (HCDR1J), HCDR2 of SEQ ID NO: 28 (HCDR2N), and HCDR3 of SEQ ID NO: 42 (HCDR3L). In some embodiments, the antibody or its antigen-binding fragment comprises LCDR1 of SEQ ID NO: 55 (LCDR1J), LCDR2 of SEQ ID NO: 66 (LCDR2I), and LCDR3 of SEQ ID NO: 79 (LCDR3K).

[0289] In some embodiments, the antibody or its antigen-binding fragment competes with a reference antibody, wherein the reference antibody comprises HCDR1 of SEQ ID NO: 10 (HCDR1J), HCDR2 of SEQ ID NO: 28 (HCDR2N), HCDR3 of SEQ ID NO: 42 (HCDR3L), LCDR1 of SEQ ID NO: 55 (LCDR1J), LCDR2 of SEQ ID NO: 66 (LCDR2I), and LCDR3 of SEQ ID NO: 79 (LCDR3K).

[0290] In some embodiments, the antibody or its antigen-binding fragment comprises HCDR1 of SEQ ID NO: 11 (HCDR1K), HCDR2 of SEQ ID NO: 29 (HCDR2O), and HCDR3 of SEQ ID NO: 42 (HCDR3L). In some embodiments, the antibody or its antigen-binding fragment comprises LCDR1 of SEQ ID NO: 56 (LCDR1K), LCDR2 of SEQ ID NO: 66 (LCDR2I), and LCDR3 of SEQ ID NO: 80 (LCDR3L).

[0291] In some embodiments, the antibody or its antigen-binding fragment competes with a reference antibody, wherein the reference antibody comprises HCDR1 of SEQ ID NO: 11 (HCDR1K), HCDR2 of SEQ ID NO: 29 (HCDR2O), HCDR3 of SEQ ID NO: 42 (HCDR3L), LCDR1 of SEQ ID NO: 56 (LCDR1K), LCDR2 of SEQ ID NO: 66 (LCDR2I), and LCDR3 of SEQ ID NO: 80 (LCDR3L).

[0292] In some embodiments, the antibody or its antigen-binding fragment comprises HCDR1 of SEQ ID NO: 10 (HCDR1J), HCDR2 of SEQ ID NO: 28 (HCDR2N), and HCDR3 of SEQ ID NO: 42 (HCDR3L). In some embodiments, the antibody or its antigen-binding fragment comprises LCDR1 of SEQ ID NO: 55 (LCDR1J), LCDR2 of SEQ ID NO: 66 (LCDR2I), and LCDR3 of SEQ ID NO: 79 (LCDR3K).

[0293] In some embodiments, the antibody or its antigen-binding fragment competes with a reference antibody, wherein the reference antibody comprises HCDR1 of SEQ ID NO: 10 (HCDR1J), HCDR2 of SEQ ID NO: 28 (HCDR2N), HCDR3 of SEQ ID NO: 42 (HCDR3L), LCDR1 of SEQ ID NO: 55 (LCDR1J), LCDR2 of SEQ ID NO: 66 (LCDR2I), and LCDR3 of SEQ ID NO: 79 (LCDR3K).

[0294] In some embodiments, the antibody or its antigen-binding fragment comprises HCDR1 of SEQ ID NO: 12 (HCDR1L), HCDR2 of SEQ ID NO: 28 (HCDR2N), and HCDR3 of SEQ ID NO: 42 (HCDR3L). In some embodiments, the antibody or its antigen-binding fragment comprises LCDR1 of SEQ ID NO: 55 (LCDR1J), LCDR2 of SEQ ID NO: 66 (LCDR2I), and LCDR3 of SEQ ID NO: 80 (LCDR3L).

[0295] In some embodiments, the antibody or its antigen-binding fragment competes with a reference antibody, wherein the reference antibody comprises HCDR1 of SEQ ID NO: 12 (HCDR1L), HCDR2 of SEQ ID NO: 28 (HCDR2N), HCDR3 of SEQ ID NO: 42 (HCDR3L), LCDR1 of SEQ ID NO: 55 (LCDR1J), LCDR2 of SEQ ID NO: 66 (LCDR2I), and LCDR3 of SEQ ID NO: 80 (LCDR3L).

[0296] In some embodiments, the antibody or its antigen-binding fragment comprises HCDR1 of SEQ ID NO: 10 (HCDR1J), HCDR2 of SEQ ID NO: 28 (HCDR2N), and HCDR3 of SEQ ID NO: 44 (HCDR3N). In some embodiments, the antibody or its antigen-binding fragment comprises LCDR1 of SEQ ID NO: 55 (LCDR1J), LCDR2 of SEQ ID NO: 66 (LCDR2I), and LCDR3 of SEQ ID NO: 79 (LCDR3K).

[0297] In some embodiments, the antibody or its antigen-binding fragment competes with a reference antibody, wherein the reference antibody comprises HCDR1 of SEQ ID NO: 10 (HCDR1J), HCDR2 of SEQ ID NO: 28 (HCDR2N), HCDR3 of SEQ ID NO: 44 (HCDR3N), LCDR1 of SEQ ID NO: 55 (LCDR1J), LCDR2 of SEQ ID NO: 66 (LCDR2I), and LCDR3 of SEQ ID NO: 79 (LCDR3K).

[0298] In some embodiments, the antibody or its antigen-binding fragment comprises HCDR1 of SEQ ID NO: 13 (HCDR1M), HCDR2 of SEQ ID NO: 30 (HCDR2P), and HCDR3 of SEQ ID NO: 45 (HCDR3O). In some embodiments, the antibody or its antigen-binding fragment comprises LCDR1 of SEQ ID NO: 57 (LCDR1L), LCDR2 of SEQ ID NO: 68 (LCDR2K), and LCDR3 of SEQ ID NO: 81 (LCDR3M).

[0299] In some embodiments, the antibody or its antigen-binding fragment competes with a reference antibody, wherein the reference antibody comprises HCDR1 of SEQ ID NO: 13 (HCDR1M), HCDR2 of SEQ ID NO: 30 (HCDR2P), HCDR3 of SEQ ID NO: 45 (HCDR3O), LCDR1 of SEQ ID NO: 57 (LCDR1L), LCDR2 of SEQ ID NO: 68 (LCDR2K), and LCDR3 of SEQ ID NO: 81 (LCDR3M).

[0300] In some embodiments, the antibody or its antigen-binding fragment comprises HCDR1 of SEQ ID NO: 14 (HCDR1N), HCDR2 of SEQ ID NO: 30 (HCDR2P), and HCDR3 of SEQ ID NO: 29 (HCDR2O). In some embodiments, the antibody or its antigen-binding fragment comprises LCDR1 of SEQ ID NO: 57 (LCDR1L), LCDR2 of SEQ ID NO: 68 (LCDR2K), and LCDR3 of SEQ ID NO: 82 (LCDR3N).

[0301] In some embodiments, the antibody or its antigen-binding fragment competes with a reference antibody, wherein the reference antibody comprises HCDR1 of SEQ ID NO: 14 (HCDR1N), HCDR2 of SEQ ID NO: 30 (HCDR2P), HCDR3 of SEQ ID NO: 29 (HCDR2O), LCDR1 of SEQ ID NO: 57 (LCDR1L), LCDR2 of SEQ ID NO: 68 (LCDR2K), and LCDR3 of SEQ ID NO: 82 (LCDR3N). In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a CDR differing from one or more amino acids of the CDRs shown in Table C. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a CDR differing from any of the CDRs shown in Table C by no more than 5 amino acids. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a CDR differing from any of the CDRs shown in Table C by no more than 4 amino acids. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a CDR that differs from any of the CDRs shown in Table C by no more than 3 amino acids. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a CDR that differs from any of the CDRs shown in Table C by no more than 2 amino acids. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a CDR that differs from any of the CDRs shown in Table C by no more than 1 amino acid.

[0302] In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises: HCDR1 containing an amino acid sequence no more than 2 amino acids different from GYSFTRYW (SEQ ID NO: 7, HCDR1G); HCDR2 containing an amino acid sequence no more than 2 amino acids different from IDPSDSET (SEQ ID NO: 22, HCDR2H); HCDR3 containing an amino acid sequence no more than 4 amino acids different from ARGGYFGEGWYFDV (SEQ ID NO: 38, HCDR3H); LCDR1 containing an amino acid sequence no more than 2 amino acids different from QSLVHRNGNTY (SEQ ID NO: 51, LCDR1F); LCDR2 containing an amino acid sequence no more than 1 amino acid different from KVS (SEQ ID NO: 63, LCDR2F); and LCDR3 containing an amino acid sequence no more than 4 amino acids different from SQSTHVPWT (SEQ ID NO: 75, LCDR3G).

[0303] In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises: HCDR1 containing an amino acid sequence no more than 2 amino acids different from GYTFTSYW (SEQ ID NO: 8, HCDR1H); HCDR2 containing an amino acid sequence no more than 2 amino acids different from IYPSDSYT (SEQ ID NO: 23, HCDR2I); HCDR3 containing an amino acid sequence no more than 4 amino acids different from TRRANYVGAMDY (SEQ ID NO: 39, HCDR3I); LCDR1 containing an amino acid sequence no more than 2 amino acids different from SVSSY (SEQ ID NO: 52, LCDR1G); LCDR2 containing an amino acid sequence no more than 1 amino acid different from ATS (SEQ ID NO: 64, LCDR2G); and LCDR3 containing an amino acid sequence no more than 4 amino acids different from QQWSSNPLT (SEQ ID NO: 76, LCDR3H).

[0304] In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises: HCDR1 containing an amino acid sequence no more than 2 amino acids different from GFSLTSYG (SEQ ID NO: 9, HCDR1I); HCDR2 containing an amino acid sequence no more than 2 amino acids different from IWVGGIT (SEQ ID NO: 24, HCDR2J); HCDR3 containing an amino acid sequence no more than 4 amino acids different from ARDGYYGDFDV (SEQ ID NO: 40, HCDR3J); LCDR1 containing an amino acid sequence no more than 2 amino acids different from QDINKF (SEQ ID NO: 53, LCDR1H); LCDR2 containing an amino acid sequence no more than 1 amino acid different from YTS (SEQ ID NO: 65, LCDR2H); and LCDR3 containing an amino acid sequence no more than 4 amino acids different from LQYDNLRT (SEQ ID NO: 77, LCDR3I).

[0305] In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises: HCDR1 containing an amino acid sequence that differs from GFSLTSYG (SEQ ID NO: 9, HCDR1I) by no more than 2 amino acids; HCDR2 containing an amino acid sequence that differs from IWAGGIT (SEQ ID NO: 25, HCDR2K) by no more than 2 amino acids; HCDR3 containing an amino acid sequence that differs from ARDGYYGDFDV (SEQ ID NO: 40, HCDR3J) by no more than 4 amino acids; LCDR1 containing an amino acid sequence that differs from QDINKY (SEQ ID NO: 54, LCDR1I) by no more than 2 amino acids; LCDR2 containing an amino acid sequence that differs from YTS (SEQ ID NO: 65, LCDR2H) by no more than 1 amino acid; and LCDR3 containing an amino acid sequence that differs from LQYDNLRT (SEQ ID NO: 77, LCDR3I) by no more than 4 amino acids.

[0306] In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises: HCDR1 containing an amino acid sequence that differs from GFSLTSYG (SEQ ID NO: 9, HCDR1I) by no more than 2 amino acids; HCDR2 containing an amino acid sequence that differs from IWAGGIT (SEQ ID NO: 25, HCDR2K) by no more than 2 amino acids; HCDR3 containing an amino acid sequence that differs from ARDGYYGHFDV (SEQ ID NO: 41, HCDR3K) by no more than 4 amino acids; LCDR1 containing an amino acid sequence that differs from QDINKY (SEQ ID NO: 54, LCDR1I) by no more than 2 amino acids; LCDR2 containing an amino acid sequence that differs from YTS (SEQ ID NO: 65, LCDR2H) by no more than 1 amino acid; and LCDR3 containing an amino acid sequence that differs from LQYDNLRA (SEQ ID NO: 78, LCDR3J) by no more than 4 amino acids.

[0307] In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises: HCDR1 containing an amino acid sequence that differs from GFTFSSDA (SEQ ID NO: 10, HCDR1J) by no more than 2 amino acids; HCDR2 containing an amino acid sequence that differs from ISIGGSA (SEQ ID NO: 26, HCDR2L) by no more than 2 amino acids; HCDR3 containing an amino acid sequence that differs from ARGGDYDAMDY (SEQ ID NO: 42, HCDR3L) by no more than 4 amino acids; LCDR1 containing an amino acid sequence that differs from QSISDL (SEQ ID NO: 55, LCDR1J) by no more than 2 amino acids; LCDR2 containing an amino acid sequence that differs from YAS (SEQ ID NO: 66, LCDR2I) by no more than 1 amino acid; and LCDR3 containing an amino acid sequence that differs from QNGHNFPFT (SEQ ID NO: 79, LCDR3K) by no more than 4 amino acids.

[0308] In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises: HCDR1 containing an amino acid sequence that differs from GFTFSSSA (SEQ ID NO: 11, HCDR1K) by no more than 2 amino acids; HCDR2 containing an amino acid sequence that differs from ISVGGST (SEQ ID NO: 27, HCDR2M) by no more than 2 amino acids; HCDR3 containing an amino acid sequence that differs from ARGGDYDAMDY (SEQ ID NO: 42, HCDR3L) by no more than 4 amino acids; LCDR1 containing an amino acid sequence that differs from QSISDY (SEQ ID NO: 56, LCDR1K) by no more than 2 amino acids; LCDR2 containing an amino acid sequence that differs from YAS (SEQ ID NO: 66, LCDR2I) by no more than 1 amino acid; and LCDR3 containing an amino acid sequence that differs from QNGHSFPFT (SEQ ID NO: 80, LCDR3L) by no more than 4 amino acids.

[0309] In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises: HCDR1 containing an amino acid sequence that differs from GFTFSSSA (SEQ ID NO: 11, HCDR1K) by no more than 2 amino acids; HCDR2 containing an amino acid sequence that differs from ISVGGST (SEQ ID NO: 27, HCDR2M) by no more than 2 amino acids; HCDR3 containing an amino acid sequence that differs from ARGGDYDAMDY (SEQ ID NO: 42, HCDR3L) by no more than 4 amino acids; LCDR1 containing an amino acid sequence that differs from QSISDY (SEQ ID NO: 56, LCDR1K) by no more than 2 amino acids; LCDR2 containing an amino acid sequence that differs from YSS (SEQ ID NO: 67, LCDR2J) by no more than 1 amino acid; and LCDR3 containing an amino acid sequence that differs from QNGHSFPFT (SEQ ID NO: 80, LCDR3L) by no more than 4 amino acids.

[0310] In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises: HCDR1 containing an amino acid sequence that differs from GFTFSSSA (SEQ ID NO: 11, HCDR1K) by no more than 2 amino acids; HCDR2 containing an amino acid sequence that differs from ISVGGST (SEQ ID NO: 27, HCDR2M) by no more than 2 amino acids; HCDR3 containing an amino acid sequence that differs from ARGGDYDPMDY (SEQ ID NO: 43, HCDR3M) by no more than 4 amino acids; LCDR1 containing an amino acid sequence that differs from QSISDY (SEQ ID NO: 56, LCDR1K) by no more than 2 amino acids; LCDR2 containing an amino acid sequence that differs from YAS (SEQ ID NO: 66, LCDR2I) by no more than 1 amino acid; and LCDR3 containing an amino acid sequence that differs from QNGHSFPFT (SEQ ID NO: 80, LCDR3L) by no more than 4 amino acids.

[0311] In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises: HCDR1 containing an amino acid sequence that differs from GFTFSSDA (SEQ ID NO: 10, HCDR1J) by no more than 2 amino acids; HCDR2 containing an amino acid sequence that differs from ISIGGST (SEQ ID NO: 28, HCDR2N) by no more than 2 amino acids; HCDR3 containing an amino acid sequence that differs from ARGGDYDAMDY (SEQ ID NO: 42, HCDR3L) by no more than 4 amino acids; LCDR1 containing an amino acid sequence that differs from QSISDL (SEQ ID NO: 55, LCDR1J) by no more than 2 amino acids; LCDR2 containing an amino acid sequence that differs from YAS (SEQ ID NO: 66, LCDR2I) by no more than 1 amino acid; and LCDR3 containing an amino acid sequence that differs from QNGHNFPFT (SEQ ID NO: 79, LCDR3K) by no more than 4 amino acids.

[0312] In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises: HCDR1 containing an amino acid sequence that differs from GFTFSSSA (SEQ ID NO: 11, HCDR1K) by no more than 2 amino acids; HCDR2 containing an amino acid sequence that differs from ISVGGSI (SEQ ID NO: 29, HCDR2O) by no more than 2 amino acids; HCDR3 containing an amino acid sequence that differs from ARGGDYDAMDY (SEQ ID NO: 42, HCDR3L) by no more than 4 amino acids; LCDR1 containing an amino acid sequence that differs from QSISDY (SEQ ID NO: 56, LCDR1K) by no more than 2 amino acids; LCDR2 containing an amino acid sequence that differs from YAS (SEQ ID NO: 66, LCDR2I) by no more than 1 amino acid; and LCDR3 containing an amino acid sequence that differs from QNGHSFPFT (SEQ ID NO: 80, LCDR3L) by no more than 4 amino acids.

[0313] In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises: HCDR1 containing an amino acid sequence no more than 2 amino acids different from GYSFTRYW (SEQ ID NO: 7, HCDR1G); HCDR2 containing an amino acid sequence no more than 2 amino acids different from IDPSDSET (SEQ ID NO: 22, HCDR2H); HCDR3 containing an amino acid sequence no more than 4 amino acids different from ARGGYFGEGWYFDV (SEQ ID NO: 38, HCDR3H); LCDR1 containing an amino acid sequence no more than 2 amino acids different from QSLVHRNGNTY (SEQ ID NO: 51, LCDR1F); LCDR2 containing an amino acid sequence no more than 1 amino acid different from KVS (SEQ ID NO: 63, LCDR2F); and LCDR3 containing an amino acid sequence no more than 4 amino acids different from SQSTHVPWT (SEQ ID NO: 75, LCDR3G).

[0314] In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises: HCDR1 containing an amino acid sequence that differs from GFTFSSDA (SEQ ID NO: 10, HCDR1J) by no more than 2 amino acids; HCDR2 containing an amino acid sequence that differs from ISIGGST (SEQ ID NO: 28, HCDR2N) by no more than 2 amino acids; HCDR3 containing an amino acid sequence that differs from ARGGDYDAMDY (SEQ ID NO: 42, HCDR3L) by no more than 4 amino acids; LCDR1 containing an amino acid sequence that differs from QSISDL (SEQ ID NO: 55, LCDR1J) by no more than 2 amino acids; LCDR2 containing an amino acid sequence that differs from YAS (SEQ ID NO: 66, LCDR2I) by no more than 1 amino acid; and LCDR3 containing an amino acid sequence that differs from QNGHNFPFT (SEQ ID NO: 79, LCDR3K) by no more than 4 amino acids.

[0315] In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises: HCDR1 containing an amino acid sequence that differs from GFTFSNCA (SEQ ID NO: 12, HCDR1L) by no more than 2 amino acids; HCDR2 containing an amino acid sequence that differs from ISIGGST (SEQ ID NO: 28, HCDR2N) by no more than 2 amino acids; HCDR3 containing an amino acid sequence that differs from ARGGDYDAMDY (SEQ ID NO: 42, HCDR3L) by no more than 4 amino acids; LCDR1 containing an amino acid sequence that differs from QSISDL (SEQ ID NO: 55, LCDR1J) by no more than 2 amino acids; LCDR2 containing an amino acid sequence that differs from YAS (SEQ ID NO: 66, LCDR2I) by no more than 1 amino acid; and LCDR3 containing an amino acid sequence that differs from QNGHSFPFT (SEQ ID NO: 80, LCDR3L) by no more than 4 amino acids.

[0316] In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises: HCDR1 containing an amino acid sequence that differs from GFTFSSDA (SEQ ID NO: 10, HCDR1J) by no more than 2 amino acids; HCDR2 containing an amino acid sequence that differs from ISIGGST (SEQ ID NO: 28, HCDR2N) by no more than 2 amino acids; HCDR3 containing an amino acid sequence that differs from TRGGDYDAMDY (SEQ ID NO: 44, HCDR3N) by no more than 4 amino acids; LCDR1 containing an amino acid sequence that differs from QSISDL (SEQ ID NO: 55, LCDR1J) by no more than 2 amino acids; LCDR2 containing an amino acid sequence that differs from YAS (SEQ ID NO: 66, LCDR2I) by no more than 1 amino acid; and LCDR3 containing an amino acid sequence that differs from QNGHNFPFT (SEQ ID NO: 79, LCDR3K) by no more than 4 amino acids.

[0317] In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises: HCDR1 containing an amino acid sequence that differs from GFSLSTSDMG (SEQ ID NO: 13, HCDR1M) by no more than 2 amino acids; HCDR2 containing an amino acid sequence that differs from IYWDDDK (SEQ ID NO: 30, HCDR2P) by no more than 2 amino acids; HCDR3 containing an amino acid sequence that differs from VRGTAVVAFYWYFDV (SEQ ID NO: 45, HCDR3O) by no more than 4 amino acids; LCDR1 containing an amino acid sequence that differs from QDINNY (SEQ ID NO: 57, LCDR1L) by no more than 2 amino acids; LCDR2 containing an amino acid sequence that differs from RAN (SEQ ID NO: 68, LCDR2K) by no more than 1 amino acid; and LCDR3 containing an amino acid sequence that differs from LHYDDFPLT (SEQ ID NO: 81, LCDR3M) by no more than 4 amino acids.

[0318] In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises: HCDR1 containing an amino acid sequence that differs from GFSLSTSDLG (SEQ ID NO: 14, HCDR1N) by no more than 2 amino acids; HCDR2 containing an amino acid sequence that differs from IYWDDDK (SEQ ID NO: 30, HCDR2P) by no more than 2 amino acids; HCDR3 containing an amino acid sequence that differs from VRGTAVVAFYWYFDV (SEQ ID NO: 45, HCDR3O) by no more than 4 amino acids; LCDR1 containing an amino acid sequence that differs from QDINNY (SEQ ID NO: 57, LCDR1L) by no more than 2 amino acids; LCDR2 containing an amino acid sequence that differs from RAN (SEQ ID NO: 68, LCDR2K) by no more than 1 amino acid; and LCDR3 containing an amino acid sequence that differs from LQYDDFPLT (SEQ ID NO: 82, LCDR3N) by no more than 4 amino acids.

[0319] Table D. Exemplary VH and VL sequences of mouse anti-α7β1 integrin antibodies .

[0320]

[0321]

[0322]

[0323] In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH8) containing at least 80% of the same amino acid sequence as SEQ ID NO: 142. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH8) containing at least 83% of the same amino acid sequence as SEQ ID NO: 142. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH8) containing at least 85% of the same amino acid sequence as SEQ ID NO: 142. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH8) containing at least 87% of the same amino acid sequence as SEQ ID NO: 142. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH8) containing at least 90% of the same amino acid sequence as SEQ ID NO: 142. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH8) containing at least 95% of the same amino acid sequence as SEQ ID NO: 142. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH8) containing at least 98% of the same amino acid sequence as SEQ ID NO: 142. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH8) containing at least 99% of the same amino acid sequence as SEQ ID NO: 142. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH8) containing the same amino acid sequence as SEQ ID NO: 142.

[0324] In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH9) containing at least 80% of the same amino acid sequence as SEQ ID NO: 154. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH9) containing at least 83% of the same amino acid sequence as SEQ ID NO: 154. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH9) containing at least 85% of the same amino acid sequence as SEQ ID NO: 154. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH9) containing at least 87% of the same amino acid sequence as SEQ ID NO: 154. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH9) containing at least 90% of the same amino acid sequence as SEQ ID NO: 154. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH9) containing at least 95% of the same amino acid sequence as SEQ ID NO: 154. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH9) containing at least 98% of the same amino acid sequence as SEQ ID NO: 154. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH9) containing at least 99% of the same amino acid sequence as SEQ ID NO: 154. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH9) containing the same amino acid sequence as SEQ ID NO: 154.

[0325] In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH10) containing at least 80% of the same amino acid sequence as SEQ ID NO:148. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH10) containing at least 83% of the same amino acid sequence as SEQ ID NO:148. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH10) containing at least 85% of the same amino acid sequence as SEQ ID NO:148. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH10) containing at least 87% of the same amino acid sequence as SEQ ID NO:148. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH10) containing at least 90% of the same amino acid sequence as SEQ ID NO:148. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH10) containing at least 95% of the same amino acid sequence as SEQ ID NO: 148. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH10) containing at least 98% of the same amino acid sequence as SEQ ID NO: 148. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH10) containing at least 99% of the same amino acid sequence as SEQ ID NO: 148. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH10) containing the same amino acid sequence as SEQ ID NO: 148.

[0326] In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH11) containing at least 80% of the same amino acid sequence as SEQ ID NO:150. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH11) containing at least 83% of the same amino acid sequence as SEQ ID NO:150. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH11) containing at least 85% of the same amino acid sequence as SEQ ID NO:150. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH11) containing at least 87% of the same amino acid sequence as SEQ ID NO:150. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH11) containing at least 90% of the same amino acid sequence as SEQ ID NO:150. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH11) containing at least 95% of the same amino acid sequence as SEQ ID NO: 150. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH11) containing at least 98% of the same amino acid sequence as SEQ ID NO: 150. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH11) containing at least 99% of the same amino acid sequence as SEQ ID NO: 150. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH11) containing the same amino acid sequence as SEQ ID NO: 150.

[0327] In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH12) containing at least 80% of the same amino acid sequence as SEQ ID NO:152. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH12) containing at least 83% of the same amino acid sequence as SEQ ID NO:152. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH12) containing at least 85% of the same amino acid sequence as SEQ ID NO:152. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH12) containing at least 87% of the same amino acid sequence as SEQ ID NO:152. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH12) containing at least 90% of the same amino acid sequence as SEQ ID NO:152. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH12) containing at least 95% of the same amino acid sequence as SEQ ID NO: 152. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH12) containing at least 98% of the same amino acid sequence as SEQ ID NO: 152. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH12) containing at least 99% of the same amino acid sequence as SEQ ID NO: 152. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH12) containing the same amino acid sequence as SEQ ID NO: 152.

[0328] In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH13) containing at least 80% of the same amino acid sequence as SEQ ID NO:156. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH13) containing at least 83% of the same amino acid sequence as SEQ ID NO:156. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH13) containing at least 85% of the same amino acid sequence as SEQ ID NO:156. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH13) containing at least 87% of the same amino acid sequence as SEQ ID NO:156. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH13) containing at least 90% of the same amino acid sequence as SEQ ID NO:156. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH13) containing at least 95% of the same amino acid sequence as SEQ ID NO: 156. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH13) containing at least 98% of the same amino acid sequence as SEQ ID NO: 156. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH13) containing at least 99% of the same amino acid sequence as SEQ ID NO: 156. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH13) containing the same amino acid sequence as SEQ ID NO: 156.

[0329] In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH14) containing at least 80% of the same amino acid sequence as SEQ ID NO:158. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH14) containing at least 83% of the same amino acid sequence as SEQ ID NO:158. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH14) containing at least 85% of the same amino acid sequence as SEQ ID NO:158. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH14) containing at least 87% of the same amino acid sequence as SEQ ID NO:158. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH14) containing at least 90% of the same amino acid sequence as SEQ ID NO:158. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH14) containing at least 95% of the same amino acid sequence as SEQ ID NO: 158. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH14) containing at least 98% of the same amino acid sequence as SEQ ID NO: 158. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH14) containing at least 99% of the same amino acid sequence as SEQ ID NO: 158. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH14) containing the same amino acid sequence as SEQ ID NO: 158.

[0330] In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH15) containing at least 80% of the same amino acid sequence as SEQ ID NO:160. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH15) containing at least 83% of the same amino acid sequence as SEQ ID NO:160. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH15) containing at least 85% of the same amino acid sequence as SEQ ID NO:160. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH15) containing at least 87% of the same amino acid sequence as SEQ ID NO:160. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH15) containing at least 90% of the same amino acid sequence as SEQ ID NO:160. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH15) containing at least 95% of the same amino acid sequence as SEQ ID NO: 160. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH15) containing at least 98% of the same amino acid sequence as SEQ ID NO: 160. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH15) containing at least 99% of the same amino acid sequence as SEQ ID NO: 160. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH15) containing the same amino acid sequence as SEQ ID NO: 160.

[0331] In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH16) containing at least 80% of the same amino acid sequence as SEQ ID NO:162. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH16) containing at least 83% of the same amino acid sequence as SEQ ID NO:162. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH16) containing at least 85% of the same amino acid sequence as SEQ ID NO:162. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH16) containing at least 87% of the same amino acid sequence as SEQ ID NO:162. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH16) containing at least 90% of the same amino acid sequence as SEQ ID NO:162. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH16) containing at least 95% of the same amino acid sequence as SEQ ID NO: 162. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH16) containing at least 98% of the same amino acid sequence as SEQ ID NO: 162. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH16) containing at least 99% of the same amino acid sequence as SEQ ID NO: 162. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH16) containing the same amino acid sequence as SEQ ID NO: 162.

[0332] In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH17) containing at least 80% of the same amino acid sequence as SEQ ID NO:164. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH17) containing at least 83% of the same amino acid sequence as SEQ ID NO:164. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH17) containing at least 85% of the same amino acid sequence as SEQ ID NO:164. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH17) containing at least 87% of the same amino acid sequence as SEQ ID NO:164. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH17) containing at least 90% of the same amino acid sequence as SEQ ID NO:164. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH17) containing at least 95% of the same amino acid sequence as SEQ ID NO: 164. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH17) containing at least 98% of the same amino acid sequence as SEQ ID NO: 164. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH17) containing at least 99% of the same amino acid sequence as SEQ ID NO: 164. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH17) containing the same amino acid sequence as SEQ ID NO: 164.

[0333] In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH18) containing at least 80% of the same amino acid sequence as SEQ ID NO:166. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH18) containing at least 83% of the same amino acid sequence as SEQ ID NO:166. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH18) containing at least 85% of the same amino acid sequence as SEQ ID NO:166. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH18) containing at least 87% of the same amino acid sequence as SEQ ID NO:166. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH18) containing at least 90% of the same amino acid sequence as SEQ ID NO:166. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH18) containing at least 95% of the same amino acid sequence as SEQ ID NO: 166. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH18) containing at least 98% of the same amino acid sequence as SEQ ID NO: 166. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH18) containing at least 99% of the same amino acid sequence as SEQ ID NO: 166. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH18) containing the same amino acid sequence as SEQ ID NO: 166.

[0334] In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH20) containing at least 80% of the same amino acid sequence as SEQ ID NO:170. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH20) containing at least 83% of the same amino acid sequence as SEQ ID NO:170. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH20) containing at least 85% of the same amino acid sequence as SEQ ID NO:170. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH20) containing at least 87% of the same amino acid sequence as SEQ ID NO:170. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH20) containing at least 90% of the same amino acid sequence as SEQ ID NO:170. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH20) containing at least 95% of the same amino acid sequence as SEQ ID NO: 170. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH20) containing at least 98% of the same amino acid sequence as SEQ ID NO: 170. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH20) containing at least 99% of the same amino acid sequence as SEQ ID NO: 170. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH20) containing the same amino acid sequence as SEQ ID NO: 170.

[0335] In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH21) containing at least 80% of the same amino acid sequence as SEQ ID NO:172. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH21) containing at least 83% of the same amino acid sequence as SEQ ID NO:172. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH21) containing at least 85% of the same amino acid sequence as SEQ ID NO:172. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH21) containing at least 87% of the same amino acid sequence as SEQ ID NO:172. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH21) containing at least 90% of the same amino acid sequence as SEQ ID NO:172. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH21) containing at least 95% of the same amino acid sequence as SEQ ID NO: 172. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH21) containing at least 98% of the same amino acid sequence as SEQ ID NO: 172. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH21) containing at least 99% of the same amino acid sequence as SEQ ID NO: 172. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH21) containing the same amino acid sequence as SEQ ID NO: 172.

[0336] In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH22) containing at least 80% of the same amino acid sequence as SEQ ID NO:144. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH22) containing at least 83% of the same amino acid sequence as SEQ ID NO:144. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH22) containing at least 85% of the same amino acid sequence as SEQ ID NO:144. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH22) containing at least 87% of the same amino acid sequence as SEQ ID NO:144. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH22) containing at least 90% of the same amino acid sequence as SEQ ID NO:144. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH22) containing at least 95% of the same amino acid sequence as SEQ ID NO: 144. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH22) containing at least 98% of the same amino acid sequence as SEQ ID NO: 144. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH22) containing at least 99% of the same amino acid sequence as SEQ ID NO: 144. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH22) containing the same amino acid sequence as SEQ ID NO: 144.

[0337] In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH23) containing at least 80% of the same amino acid sequence as SEQ ID NO:146. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH23) containing at least 83% of the same amino acid sequence as SEQ ID NO:146. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH23) containing at least 85% of the same amino acid sequence as SEQ ID NO:146. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH23) containing at least 87% of the same amino acid sequence as SEQ ID NO:146. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH23) containing at least 90% of the same amino acid sequence as SEQ ID NO:146. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH23) containing at least 95% of the same amino acid sequence as SEQ ID NO: 146. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH23) containing at least 98% of the same amino acid sequence as SEQ ID NO: 146. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH23) containing at least 99% of the same amino acid sequence as SEQ ID NO: 146. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region (VH23) containing the same amino acid sequence as SEQ ID NO: 146.

[0338] In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL8) containing at least 80% of the same amino acid sequence as SEQ ID NO: 143. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL8) containing at least 83% of the same amino acid sequence as SEQ ID NO: 134. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL8) containing at least 85% of the same amino acid sequence as SEQ ID NO: 143. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL8) containing at least 87% of the same amino acid sequence as SEQ ID NO: 143. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL8) containing at least 90% of the same amino acid sequence as SEQ ID NO: 143. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL8) containing at least 95% of the same amino acid sequence as SEQ ID NO: 143. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL8) containing at least 98% of the same amino acid sequence as SEQ ID NO: 143. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL8) containing at least 99% of the same amino acid sequence as SEQ ID NO: 143. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL8) containing the same amino acid sequence as SEQ ID NO: 143.

[0339] In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL9) containing at least 80% of the same amino acid sequence as SEQ ID NO: 155. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL9) containing at least 83% of the same amino acid sequence as SEQ ID NO: 155. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL9) containing at least 85% of the same amino acid sequence as SEQ ID NO: 155. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL9) containing at least 87% of the same amino acid sequence as SEQ ID NO: 155. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL9) containing at least 90% of the same amino acid sequence as SEQ ID NO: 155. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL9) containing at least 95% of the same amino acid sequence as SEQ ID NO: 155. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL9) containing at least 98% of the same amino acid sequence as SEQ ID NO: 155. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL9) containing at least 99% of the same amino acid sequence as SEQ ID NO: 155. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL9) containing the same amino acid sequence as SEQ ID NO: 155.

[0340] In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL10) containing at least 80% of the same amino acid sequence as SEQ ID NO:149. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL10) containing at least 83% of the same amino acid sequence as SEQ ID NO:149. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL10) containing at least 85% of the same amino acid sequence as SEQ ID NO:149. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL10) containing at least 87% of the same amino acid sequence as SEQ ID NO:149. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL10) containing at least 90% of the same amino acid sequence as SEQ ID NO:149. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL10) containing at least 95% of the same amino acid sequence as SEQ ID NO: 149. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL10) containing at least 98% of the same amino acid sequence as SEQ ID NO: 149. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL10) containing at least 99% of the same amino acid sequence as SEQ ID NO: 149. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL10) containing the same amino acid sequence as SEQ ID NO: 149.

[0341] In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL11) containing at least 80% of the same amino acid sequence as SEQ ID NO:151. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL11) containing at least 83% of the same amino acid sequence as SEQ ID NO:151. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL11) containing at least 85% of the same amino acid sequence as SEQ ID NO:151. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL11) containing at least 87% of the same amino acid sequence as SEQ ID NO:151. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL11) containing at least 90% of the same amino acid sequence as SEQ ID NO:151. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL11) containing at least 95% of the same amino acid sequence as SEQ ID NO: 151. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL11) containing at least 98% of the same amino acid sequence as SEQ ID NO: 151. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL11) containing at least 99% of the same amino acid sequence as SEQ ID NO: 151. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL11) containing the same amino acid sequence as SEQ ID NO: 151.

[0342] In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL12) containing at least 80% of the same amino acid sequence as SEQ ID NO:153. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL12) containing at least 83% of the same amino acid sequence as SEQ ID NO:153. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL12) containing at least 85% of the same amino acid sequence as SEQ ID NO:153. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL12) containing at least 87% of the same amino acid sequence as SEQ ID NO:153. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL12) containing at least 90% of the same amino acid sequence as SEQ ID NO:153. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL12) containing at least 95% of the same amino acid sequence as SEQ ID NO: 153. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL12) containing at least 98% of the same amino acid sequence as SEQ ID NO: 153. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL12) containing at least 99% of the same amino acid sequence as SEQ ID NO: 153. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL12) containing the same amino acid sequence as SEQ ID NO: 153.

[0343] In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL13) containing at least 80% of the same amino acid sequence as SEQ ID NO:157. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL13) containing at least 83% of the same amino acid sequence as SEQ ID NO:157. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL13) containing at least 85% of the same amino acid sequence as SEQ ID NO:157. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL13) containing at least 87% of the same amino acid sequence as SEQ ID NO:157. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL13) containing at least 90% of the same amino acid sequence as SEQ ID NO:157. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL13) containing at least 95% of the same amino acid sequence as SEQ ID NO: 157. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL13) containing at least 98% of the same amino acid sequence as SEQ ID NO: 157. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL13) containing at least 99% of the same amino acid sequence as SEQ ID NO: 157. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL13) containing the same amino acid sequence as SEQ ID NO: 157.

[0344] In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL14) containing at least 80% of the same amino acid sequence as SEQ ID NO:159. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL14) containing at least 83% of the same amino acid sequence as SEQ ID NO:159. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL14) containing at least 85% of the same amino acid sequence as SEQ ID NO:159. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL14) containing at least 87% of the same amino acid sequence as SEQ ID NO:159. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL14) containing at least 90% of the same amino acid sequence as SEQ ID NO:159. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL14) containing at least 95% of the same amino acid sequence as SEQ ID NO: 159. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL14) containing at least 98% of the same amino acid sequence as SEQ ID NO: 159. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL14) containing at least 99% of the same amino acid sequence as SEQ ID NO: 159. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL14) containing the same amino acid sequence as SEQ ID NO: 159.

[0345] In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL15) containing at least 80% of the same amino acid sequence as SEQ ID NO:161. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL15) containing at least 83% of the same amino acid sequence as SEQ ID NO:161. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL15) containing at least 85% of the same amino acid sequence as SEQ ID NO:161. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL15) containing at least 87% of the same amino acid sequence as SEQ ID NO:161. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL15) containing at least 90% of the same amino acid sequence as SEQ ID NO:161. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL15) containing at least 95% of the same amino acid sequence as SEQ ID NO: 161. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL15) containing at least 98% of the same amino acid sequence as SEQ ID NO: 161. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL15) containing at least 99% of the same amino acid sequence as SEQ ID NO: 161. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL15) containing the same amino acid sequence as SEQ ID NO: 161.

[0346] In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL16) containing at least 80% of the same amino acid sequence as SEQ ID NO:163. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL16) containing at least 83% of the same amino acid sequence as SEQ ID NO:163. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL16) containing at least 85% of the same amino acid sequence as SEQ ID NO:163. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL16) containing at least 87% of the same amino acid sequence as SEQ ID NO:163. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL16) containing at least 90% of the same amino acid sequence as SEQ ID NO:163. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL16) containing at least 95% of the same amino acid sequence as SEQ ID NO: 163. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL16) containing at least 98% of the same amino acid sequence as SEQ ID NO: 163. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL16) containing at least 99% of the same amino acid sequence as SEQ ID NO: 163. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL16) containing the same amino acid sequence as SEQ ID NO: 163.

[0347] In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL17) containing at least 80% of the same amino acid sequence as SEQ ID NO:165. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL17) containing at least 83% of the same amino acid sequence as SEQ ID NO:165. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL17) containing at least 85% of the same amino acid sequence as SEQ ID NO:165. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL17) containing at least 87% of the same amino acid sequence as SEQ ID NO:165. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL17) containing at least 90% of the same amino acid sequence as SEQ ID NO:165. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL17) containing at least 95% of the same amino acid sequence as SEQ ID NO: 165. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL17) containing at least 98% of the same amino acid sequence as SEQ ID NO: 165. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL17) containing at least 99% of the same amino acid sequence as SEQ ID NO: 165. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL17) containing the same amino acid sequence as SEQ ID NO: 165.

[0348] In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL18) containing at least 80% of the same amino acid sequence as SEQ ID NO:167. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL18) containing at least 83% of the same amino acid sequence as SEQ ID NO:167. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL18) containing at least 85% of the same amino acid sequence as SEQ ID NO:167. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL18) containing at least 87% of the same amino acid sequence as SEQ ID NO:167. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL18) containing at least 90% of the same amino acid sequence as SEQ ID NO:167. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL18) containing at least 95% of the same amino acid sequence as SEQ ID NO: 167. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL18) containing at least 98% of the same amino acid sequence as SEQ ID NO: 167. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL18) containing at least 99% of the same amino acid sequence as SEQ ID NO: 167. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL18) containing the same amino acid sequence as SEQ ID NO: 167.

[0349] In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL18) containing at least 80% of the same amino acid sequence as SEQ ID NO:167. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL18) containing at least 83% of the same amino acid sequence as SEQ ID NO:167. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL18) containing at least 85% of the same amino acid sequence as SEQ ID NO:167. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL18) containing at least 87% of the same amino acid sequence as SEQ ID NO:167. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL18) containing at least 90% of the same amino acid sequence as SEQ ID NO:167. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL18) containing at least 95% of the same amino acid sequence as SEQ ID NO: 167. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL18) containing at least 98% of the same amino acid sequence as SEQ ID NO: 167. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL18) containing at least 99% of the same amino acid sequence as SEQ ID NO: 167. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL18) containing the same amino acid sequence as SEQ ID NO: 167.

[0350] In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL19) containing at least 80% of the same amino acid sequence as SEQ ID NO:169. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL19) containing at least 83% of the same amino acid sequence as SEQ ID NO:169. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL19) containing at least 85% of the same amino acid sequence as SEQ ID NO:169. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL19) containing at least 87% of the same amino acid sequence as SEQ ID NO:169. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL19) containing at least 90% of the same amino acid sequence as SEQ ID NO:169. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL19) containing at least 95% of the same amino acid sequence as SEQ ID NO: 169. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL19) containing at least 98% of the same amino acid sequence as SEQ ID NO: 169. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL19) containing at least 99% of the same amino acid sequence as SEQ ID NO: 169. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL19) containing the same amino acid sequence as SEQ ID NO: 169.

[0351] In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL20) containing at least 80% of the same amino acid sequence as SEQ ID NO:171. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL20) containing at least 83% of the same amino acid sequence as SEQ ID NO:171. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL20) containing at least 85% of the same amino acid sequence as SEQ ID NO:171. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL20) containing at least 87% of the same amino acid sequence as SEQ ID NO:171. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL20) containing at least 90% of the same amino acid sequence as SEQ ID NO:171. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL20) containing at least 95% of the same amino acid sequence as SEQ ID NO: 171. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL20) containing at least 98% of the same amino acid sequence as SEQ ID NO: 171. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL20) containing at least 99% of the same amino acid sequence as SEQ ID NO: 171. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL20) containing the same amino acid sequence as SEQ ID NO: 171.

[0352] In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL21) containing at least 80% of the same amino acid sequence as SEQ ID NO:173. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL21) containing at least 83% of the same amino acid sequence as SEQ ID NO:173. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL21) containing at least 85% of the same amino acid sequence as SEQ ID NO:173. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL21) containing at least 87% of the same amino acid sequence as SEQ ID NO:173. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL21) containing at least 90% of the same amino acid sequence as SEQ ID NO:173. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL21) containing at least 95% of the same amino acid sequence as SEQ ID NO: 173. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL21) containing at least 98% of the same amino acid sequence as SEQ ID NO: 173. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL21) containing at least 99% of the same amino acid sequence as SEQ ID NO: 73. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL21) containing the same amino acid sequence as SEQ ID NO: 173.

[0353] In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL22) containing at least 80% of the same amino acid sequence as SEQ ID NO:145. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL22) containing at least 83% of the same amino acid sequence as SEQ ID NO:145. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL22) containing at least 85% of the same amino acid sequence as SEQ ID NO:145. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL22) containing at least 87% of the same amino acid sequence as SEQ ID NO:145. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL22) containing at least 90% of the same amino acid sequence as SEQ ID NO:145. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL22) containing at least 95% of the same amino acid sequence as SEQ ID NO: 145. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL22) containing at least 98% of the same amino acid sequence as SEQ ID NO: 145. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL22) containing at least 99% of the same amino acid sequence as SEQ ID NO: 145. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL22) containing the same amino acid sequence as SEQ ID NO: 145.

[0354] In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL23) containing at least 80% of the same amino acid sequence as SEQ ID NO:147. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL23) containing at least 83% of the same amino acid sequence as SEQ ID NO:147. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL23) containing at least 85% of the same amino acid sequence as SEQ ID NO:147. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL23) containing at least 87% of the same amino acid sequence as SEQ ID NO:147. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL23) containing at least 90% of the same amino acid sequence as SEQ ID NO:147. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL23) containing at least 95% of the same amino acid sequence as SEQ ID NO: 147. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL23) containing at least 98% of the same amino acid sequence as SEQ ID NO: 147. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL23) containing at least 99% of the same amino acid sequence as SEQ ID NO: 147. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region (VL23) containing the same amino acid sequence as SEQ ID NO: 147.

[0355] In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a heavy variable region (VH8) containing the amino acid sequence of SEQ ID NO: 142 and a light variable region (VL8) containing the amino acid sequence of SEQ ID NO: 143.

[0356] In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a heavy variable region (VH9) containing the amino acid sequence of SEQ ID NO: 154 and a light variable region (VL9) containing the amino acid sequence of SEQ ID NO: 155.

[0357] In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a heavy variable region (VH10) containing the amino acid sequence of SEQ ID NO: 149 and a light variable region (VL10) containing the amino acid sequence of SEQ ID NO: 149.

[0358] In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a heavy variable region (VH11) containing the amino acid sequence of SEQ ID NO: 150 and a light variable region (VL11) containing the amino acid sequence of SEQ ID NO: 151.

[0359] In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a heavy variable region (VH12) containing the amino acid sequence of SEQ ID NO: 152 and a light variable region (VL12) containing the amino acid sequence of SEQ ID NO: 153.

[0360] In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a heavy variable region (VH13) containing the amino acid sequence of SEQ ID NO: 156 and a light variable region (VL13) containing the amino acid sequence of SEQ ID NO: 157.

[0361] In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a heavy variable region (VH14) containing the amino acid sequence of SEQ ID NO: 158 and a light variable region (VL14) containing the amino acid sequence of SEQ ID NO: 159.

[0362] In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a heavy variable region (VH15) containing the amino acid sequence of SEQ ID NO: 160 and a light variable region (VL15) containing the amino acid sequence of SEQ ID NO: 161.

[0363] In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a heavy variable region (VH16) containing the amino acid sequence of SEQ ID NO: 162 and a light variable region (VL16) containing the amino acid sequence of SEQ ID NO: 163.

[0364] In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a heavy variable region (VH17) containing the amino acid sequence of SEQ ID NO: 164 and a light variable region (VL17) containing the amino acid sequence of SEQ ID NO: 165.

[0365] In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a heavy variable region (VH18) containing the amino acid sequence of SEQ ID NO: 166 and a light variable region (VL18) containing the amino acid sequence of SEQ ID NO: 167.

[0366] In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a heavy variable region (VH20) containing the amino acid sequence of SEQ ID NO: 170 and a light variable region (VL20) containing the amino acid sequence of SEQ ID NO: 171.

[0367] In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a heavy variable region (VH21) containing the amino acid sequence of SEQ ID NO: 172 and a light variable region (VL21) containing the amino acid sequence of SEQ ID NO: 173.

[0368] In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a heavy variable region (VH22) containing the amino acid sequence of SEQ ID NO: 144 and a light variable region (VL22) containing the amino acid sequence of SEQ ID NO: 145.

[0369] In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a heavy variable region (VH23) containing the amino acid sequence of SEQ ID NO: 146 and a light variable region (VL23) containing the amino acid sequence of SEQ ID NO: 147.

[0370] Humanized, affinity-optimized anti-α7β1 integrin antibody

[0371] In some embodiments, the integrin α7β1 antibody or antigen-binding fragment comprises at least one, two, or three complementarity-determining regions (CDRs) from the heavy chain variable region, which has an amino acid sequence as shown in Table E or a sequence substantially homologous to it (e.g., at least about 85%, 90%, 95%, 99% or more identical to it, and / or has one or more substitutions, such as conserved substitutions). In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises at least one, two, or three CDRs from the light chain variable region, which has an amino acid sequence as shown in Table E or a sequence substantially homologous to it (e.g., at least about 85%, 90%, 95%, 99% or more identical to it, and / or has one or more substitutions, such as conserved substitutions). In one embodiment, the integrin α7β1 antibody or its antigen-binding fragment comprises at least one, two, three, four, five, or six CDRs from the heavy chain variable region and the light chain variable region, the heavy chain variable region and the light chain variable region having amino acid sequences as shown in Table E or sequences substantially homologous to them (e.g., sequences that are at least about 85%, 90%, 95%, 99% or more identical to them, and / or have one or more substitutions, such as conserved substitutions).

[0372] In some embodiments, the antibody or its antigen-binding fragment is a humanized α7β1 antibody. In some embodiments, the antibody or its antigen-binding fragment comprises a CDR selected from Table E. Unless otherwise stated, the CDR sequences shown in this application are in the IMGT numbering scheme.

[0373] Table E. Exemplary CDRs for Humanized, Affinity-Optimized Anti-α7β1 Antibodies .

[0374]

[0375]

[0376] In some embodiments, the antibody or its antigen-binding fragment comprises HCDR1 of SEQ ID NO: 101, HCDR2 of SEQ ID NO: 27, and HCDR3 of SEQ ID NO: 38. In some embodiments, the antibody or its antigen-binding fragment comprises LCDR1 of SEQ ID NO: 105, LCDR2 of SEQ ID NO: 63, and LCDR3 of SEQ ID NO: 75. In some embodiments, the antibody or its antigen-binding fragment comprises HCDR1 of SEQ ID NO: 101, HCDR2 of SEQ ID NO: 27, HCDR3 of SEQ ID NO: 38, LCDR1 of SEQ ID NO: 105, LCDR2 of SEQ ID NO: 63, and LCDR3 of SEQ ID NO: 75.

[0377] In some embodiments, the antibody or its antigen-binding fragment competes with a reference antibody, wherein the reference antibody comprises HCDR1 of SEQ ID NO: 101, HCDR2 of SEQ ID NO: 27, HCDR3 of SEQ ID NO: 38, LCDR1 of SEQ ID NO: 105, LCDR2 of SEQ ID NO: 63, and LCDR3 of SEQ ID NO: 75.

[0378] In some embodiments, the antibody or its antigen-binding fragment comprises HCDR1 of SEQ ID NO: 101, HCDR2 of SEQ ID NO: 102, and HCDR3 of SEQ ID NO: 103. In some embodiments, the antibody or its antigen-binding fragment comprises LCDR1 of SEQ ID NO: 105, LCDR2 of SEQ ID NO: 106, and LCDR3 of SEQ ID NO: 75. In some embodiments, the antibody or its antigen-binding fragment comprises HCDR1 of SEQ ID NO: 101, HCDR2 of SEQ ID NO: 102, HCDR3 of SEQ ID NO: 103, LCDR1 of SEQ ID NO: 105, LCDR2 of SEQ ID NO: 106, and LCDR3 of SEQ ID NO: 75.

[0379] In some embodiments, the antibody or its antigen-binding fragment competes with a reference antibody, wherein the reference antibody comprises HCDR1 of SEQ ID NO: 101, HCDR2 of SEQ ID NO: 102, HCDR3 of SEQ ID NO: 103, LCDR1 of SEQ ID NO: 105, LCDR2 of SEQ ID NO: 106, and LCDR3 of SEQ ID NO: 75.

[0380] In some embodiments, the antibody or its antigen-binding fragment comprises HCDR1 of SEQ ID NO: 101, HCDR2 of SEQ ID NO: 102, and HCDR3 of SEQ ID NO: 104. In some embodiments, the antibody or its antigen-binding fragment comprises LCDR1 of SEQ ID NO: 105, LCDR2 of SEQ ID NO: 106, and LCDR3 of SEQ ID NO: 107. In some embodiments, the antibody or its antigen-binding fragment comprises HCDR1 of SEQ ID NO: 101, HCDR2 of SEQ ID NO: 102, HCDR3 of SEQ ID NO: 104, LCDR1 of SEQ ID NO: 105, LCDR2 of SEQ ID NO: 106, and LCDR3 of SEQ ID NO: 107.

[0381] In some embodiments, the antibody or its antigen-binding fragment competes with a reference antibody, wherein the reference antibody comprises HCDR1 of SEQ ID NO: 101, HCDR2 of SEQ ID NO: 102, HCDR3 of SEQ ID NO: 104, LCDR1 of SEQ ID NO: 105, LCDR2 of SEQ ID NO: 106, and LCDR3 of SEQ ID NO: 107.

[0382] In some embodiments, the antibody or its antigen-binding fragment comprises HCDR1 of SEQ ID NO: 101, HCDR2 of SEQ ID NO: 102, and HCDR3 of SEQ ID NO: 188. In some embodiments, the antibody or its antigen-binding fragment comprises LCDR1 of SEQ ID NO: 105, LCDR2 of SEQ ID NO: 106, and LCDR3 of SEQ ID NO: 198. In some embodiments, the antibody or its antigen-binding fragment comprises HCDR1 of SEQ ID NO: 101, HCDR2 of SEQ ID NO: 102, HCDR3 of SEQ ID NO: 188, LCDR1 of SEQ ID NO: 105, LCDR2 of SEQ ID NO: 106, and LCDR3 of SEQ ID NO: 198.

[0383] In some embodiments, the antibody or its antigen-binding fragment competes with a reference antibody, wherein the reference antibody comprises HCDR1 of SEQ ID NO: 101, HCDR2 of SEQ ID NO: 102, HCDR3 of SEQ ID NO: 188, LCDR1 of SEQ ID NO: 105, LCDR2 of SEQ ID NO: 106, and LCDR3 of SEQ ID NO: 198.

[0384] In some embodiments, the antibody or its antigen-binding fragment comprises HCDR1 of SEQ ID NO: 101, HCDR2 of SEQ ID NO: 102, and HCDR3 of SEQ ID NO: 189. In some embodiments, the antibody or its antigen-binding fragment comprises LCDR1 of SEQ ID NO: 105, LCDR2 of SEQ ID NO: 106, and LCDR3 of SEQ ID NO: 75. In some embodiments, the antibody or its antigen-binding fragment comprises HCDR1 of SEQ ID NO: 101, HCDR2 of SEQ ID NO: 102, HCDR3 of SEQ ID NO: 189, LCDR1 of SEQ ID NO: 105, LCDR2 of SEQ ID NO: 106, and LCDR3 of SEQ ID NO: 75.

[0385] In some embodiments, the antibody or its antigen-binding fragment competes with a reference antibody, wherein the reference antibody comprises HCDR1 of SEQ ID NO: 101, HCDR2 of SEQ ID NO: 102, HCDR3 of SEQ ID NO: 189, LCDR1 of SEQ ID NO: 105, LCDR2 of SEQ ID NO: 106, and LCDR3 of SEQ ID NO: 75.

[0386] In some embodiments, the antibody or its antigen-binding fragment comprises HCDR1 of SEQ ID NO: 101, HCDR2 of SEQ ID NO: 102, and HCDR3 of SEQ ID NO: 190. In some embodiments, the antibody or its antigen-binding fragment comprises LCDR1 of SEQ ID NO: 105, LCDR2 of SEQ ID NO: 106, and LCDR3 of SEQ ID NO: 75. In some embodiments, the antibody or its antigen-binding fragment comprises HCDR1 of SEQ ID NO: 101, HCDR2 of SEQ ID NO: 102, HCDR3 of SEQ ID NO: 190, LCDR1 of SEQ ID NO: 105, LCDR2 of SEQ ID NO: 106, and LCDR3 of SEQ ID NO: 75.

[0387] In some embodiments, the antibody or its antigen-binding fragment competes with a reference antibody, wherein the reference antibody comprises HCDR1 of SEQ ID NO: 101, HCDR2 of SEQ ID NO: 102, HCDR3 of SEQ ID NO: 190, LCDR1 of SEQ ID NO: 105, LCDR2 of SEQ ID NO: 106, and LCDR3 of SEQ ID NO: 75.

[0388] In some embodiments, the antibody or its antigen-binding fragment comprises HCDR1 of SEQ ID NO: 101, HCDR2 of SEQ ID NO: 102, and HCDR3 of SEQ ID NO: 191. In some embodiments, the antibody or its antigen-binding fragment comprises LCDR1 of SEQ ID NO: 105, LCDR2 of SEQ ID NO: 106, and LCDR3 of SEQ ID NO: 75. In some embodiments, the antibody or its antigen-binding fragment comprises HCDR1 of SEQ ID NO: 101, HCDR2 of SEQ ID NO: 102, HCDR3 of SEQ ID NO: 191, LCDR1 of SEQ ID NO: 105, LCDR2 of SEQ ID NO: 106, and LCDR3 of SEQ ID NO: 75.

[0389] In some embodiments, the antibody or its antigen-binding fragment competes with a reference antibody, wherein the reference antibody comprises HCDR1 of SEQ ID NO: 101, HCDR2 of SEQ ID NO: 102, HCDR3 of SEQ ID NO: 191, LCDR1 of SEQ ID NO: 105, LCDR2 of SEQ ID NO: 106, and LCDR3 of SEQ ID NO: 75.

[0390] In some embodiments, the antibody or its antigen-binding fragment comprises HCDR1 of SEQ ID NO: 101, HCDR2 of SEQ ID NO: 102, and HCDR3 of SEQ ID NO: 192. In some embodiments, the antibody or its antigen-binding fragment comprises LCDR1 of SEQ ID NO: 105, LCDR2 of SEQ ID NO: 106, and LCDR3 of SEQ ID NO: 75. In some embodiments, the antibody or its antigen-binding fragment comprises HCDR1 of SEQ ID NO: 101, HCDR2 of SEQ ID NO: 102, HCDR3 of SEQ ID NO: 192, LCDR1 of SEQ ID NO: 105, LCDR2 of SEQ ID NO: 106, and LCDR3 of SEQ ID NO: 75.

[0391] In some embodiments, the antibody or its antigen-binding fragment competes with a reference antibody, wherein the reference antibody comprises HCDR1 of SEQ ID NO: 101, HCDR2 of SEQ ID NO: 102, HCDR3 of SEQ ID NO: 192, LCDR1 of SEQ ID NO: 105, LCDR2 of SEQ ID NO: 106, and LCDR3 of SEQ ID NO: 75.

[0392] In some embodiments, the antibody or its antigen-binding fragment comprises HCDR1 of SEQ ID NO: 101, HCDR2 of SEQ ID NO: 102, and HCDR3 of SEQ ID NO: 193. In some embodiments, the antibody or its antigen-binding fragment comprises LCDR1 of SEQ ID NO: 105, LCDR2 of SEQ ID NO: 106, and LCDR3 of SEQ ID NO: 198. In some embodiments, the antibody or its antigen-binding fragment comprises HCDR1 of SEQ ID NO: 101, HCDR2 of SEQ ID NO: 102, HCDR3 of SEQ ID NO: 193, LCDR1 of SEQ ID NO: 105, LCDR2 of SEQ ID NO: 106, and LCDR3 of SEQ ID NO: 198.

[0393] In some embodiments, the antibody or its antigen-binding fragment competes with a reference antibody, wherein the reference antibody comprises HCDR1 of SEQ ID NO: 101, HCDR2 of SEQ ID NO: 102, HCDR3 of SEQ ID NO: 193, LCDR1 of SEQ ID NO: 105, LCDR2 of SEQ ID NO: 106, and LCDR3 of SEQ ID NO: 198.

[0394] In some embodiments, the antibody or its antigen-binding fragment comprises HCDR1 of SEQ ID NO: 101, HCDR2 of SEQ ID NO: 102, and HCDR3 of SEQ ID NO: 194. In some embodiments, the antibody or its antigen-binding fragment comprises LCDR1 of SEQ ID NO: 105, LCDR2 of SEQ ID NO: 106, and LCDR3 of SEQ ID NO: 107. In some embodiments, the antibody or its antigen-binding fragment comprises HCDR1 of SEQ ID NO: 101, HCDR2 of SEQ ID NO: 102, HCDR3 of SEQ ID NO: 194, LCDR1 of SEQ ID NO: 105, LCDR2 of SEQ ID NO: 106, and LCDR3 of SEQ ID NO: 107.

[0395] In some embodiments, the antibody or its antigen-binding fragment competes with a reference antibody, wherein the reference antibody comprises HCDR1 of SEQ ID NO: 101, HCDR2 of SEQ ID NO: 102, HCDR3 of SEQ ID NO: 194, LCDR1 of SEQ ID NO: 105, LCDR2 of SEQ ID NO: 106, and LCDR3 of SEQ ID NO: 107.

[0396] In some embodiments, the antibody or its antigen-binding fragment comprises HCDR1 of SEQ ID NO: 101, HCDR2 of SEQ ID NO: 102, and HCDR3 of SEQ ID NO: 194. In some embodiments, the antibody or its antigen-binding fragment comprises LCDR1 of SEQ ID NO: 105, LCDR2 of SEQ ID NO: 196, and LCDR3 of SEQ ID NO: 107. In some embodiments, the antibody or its antigen-binding fragment comprises HCDR1 of SEQ ID NO: 101, HCDR2 of SEQ ID NO: 102, HCDR3 of SEQ ID NO: 194, LCDR1 of SEQ ID NO: 105, LCDR2 of SEQ ID NO: 196, and LCDR3 of SEQ ID NO: 107.

[0397] In some embodiments, the antibody or its antigen-binding fragment competes with a reference antibody, wherein the reference antibody comprises HCDR1 of SEQ ID NO: 101, HCDR2 of SEQ ID NO: 102, HCDR3 of SEQ ID NO: 194, LCDR1 of SEQ ID NO: 105, LCDR2 of SEQ ID NO: 196, and LCDR3 of SEQ ID NO: 107.

[0398] In some embodiments, the antibody or its antigen-binding fragment comprises HCDR1 of SEQ ID NO: 101, HCDR2 of SEQ ID NO: 102, and HCDR3 of SEQ ID NO: 195. In some embodiments, the antibody or its antigen-binding fragment comprises LCDR1 of SEQ ID NO: 105, LCDR2 of SEQ ID NO: 63, and LCDR3 of SEQ ID NO: 75. In some embodiments, the antibody or its antigen-binding fragment comprises HCDR1 of SEQ ID NO: 101, HCDR2 of SEQ ID NO: 102, HCDR3 of SEQ ID NO: 195, LCDR1 of SEQ ID NO: 105, LCDR2 of SEQ ID NO: 63, and LCDR3 of SEQ ID NO: 75.

[0399] In some embodiments, the antibody or its antigen-binding fragment competes with a reference antibody, wherein the reference antibody comprises HCDR1 of SEQ ID NO: 101, HCDR2 of SEQ ID NO: 102, HCDR3 of SEQ ID NO: 195, LCDR1 of SEQ ID NO: 105, LCDR2 of SEQ ID NO: 63, and LCDR3 of SEQ ID NO: 75.

[0400] In some embodiments, the antibody or its antigen-binding fragment comprises HCDR1 of SEQ ID NO: 101, HCDR2 of SEQ ID NO: 102, and HCDR3 of SEQ ID NO: 104. In some embodiments, the antibody or its antigen-binding fragment comprises LCDR1 of SEQ ID NO: 105, LCDR2 of SEQ ID NO: 63, and LCDR3 of SEQ ID NO: 75. In some embodiments, the antibody or its antigen-binding fragment comprises HCDR1 of SEQ ID NO: 101, HCDR2 of SEQ ID NO: 102, HCDR3 of SEQ ID NO: 104, LCDR1 of SEQ ID NO: 105, LCDR2 of SEQ ID NO: 63, and LCDR3 of SEQ ID NO: 75.

[0401] In some embodiments, the antibody or its antigen-binding fragment competes with a reference antibody, wherein the reference antibody comprises HCDR1 of SEQ ID NO: 101, HCDR2 of SEQ ID NO: 102, HCDR3 of SEQ ID NO: 104, LCDR1 of SEQ ID NO: 105, LCDR2 of SEQ ID NO: 63, and LCDR3 of SEQ ID NO: 75.

[0402] In some embodiments, the antibody or its antigen-binding fragment comprises HCDR1 of SEQ ID NO: 101, HCDR2 of SEQ ID NO: 102, and HCDR3 of SEQ ID NO: 104. In some embodiments, the antibody or its antigen-binding fragment comprises LCDR1 of SEQ ID NO: 105, LCDR2 of SEQ ID NO: 197, and LCDR3 of SEQ ID NO: 75. In some embodiments, the antibody or its antigen-binding fragment comprises HCDR1 of SEQ ID NO: 101, HCDR2 of SEQ ID NO: 102, HCDR3 of SEQ ID NO: 104, LCDR1 of SEQ ID NO: 105, LCDR2 of SEQ ID NO: 197, and LCDR3 of SEQ ID NO: 75.

[0403] In some embodiments, the antibody or its antigen-binding fragment competes with a reference antibody, wherein the reference antibody comprises HCDR1 of SEQ ID NO: 101, HCDR2 of SEQ ID NO: 102, HCDR3 of SEQ ID NO: 104, LCDR1 of SEQ ID NO: 105, LCDR2 of SEQ ID NO: 197, and LCDR3 of SEQ ID NO: 75.

[0404] In some embodiments, the antibody or its antigen-binding fragment comprises HCDR1 of SEQ ID NO: 101, HCDR2 of SEQ ID NO: 102, and HCDR3 of SEQ ID NO: 190. In some embodiments, the antibody or its antigen-binding fragment comprises LCDR1 of SEQ ID NO: 105, LCDR2 of SEQ ID NO: 106, and LCDR3 of SEQ ID NO: 198. In some embodiments, the antibody or its antigen-binding fragment comprises HCDR1 of SEQ ID NO: 101, HCDR2 of SEQ ID NO: 102, HCDR3 of SEQ ID NO: 190, LCDR1 of SEQ ID NO: 105, LCDR2 of SEQ ID NO: 106, and LCDR3 of SEQ ID NO: 198.

[0405] In some embodiments, the antibody or its antigen-binding fragment competes with a reference antibody, wherein the reference antibody comprises HCDR1 of SEQ ID NO: 101, HCDR2 of SEQ ID NO: 102, HCDR3 of SEQ ID NO: 190, LCDR1 of SEQ ID NO: 105, LCDR2 of SEQ ID NO: 106, and LCDR3 of SEQ ID NO: 198.

[0406] In some embodiments, the antibody or its antigen-binding fragment comprises HCDR1 of SEQ ID NO: 101, HCDR2 of SEQ ID NO: 102, and HCDR3 of SEQ ID NO: 189. In some embodiments, the antibody or its antigen-binding fragment comprises LCDR1 of SEQ ID NO: 105, LCDR2 of SEQ ID NO: 197, and LCDR3 of SEQ ID NO: 107. In some embodiments, the antibody or its antigen-binding fragment comprises HCDR1 of SEQ ID NO: 101, HCDR2 of SEQ ID NO: 102, HCDR3 of SEQ ID NO: 189, LCDR1 of SEQ ID NO: 105, LCDR2 of SEQ ID NO: 197, and LCDR3 of SEQ ID NO: 107.

[0407] In some embodiments, the antibody or its antigen-binding fragment competes with a reference antibody, wherein the reference antibody comprises HCDR1 of SEQ ID NO: 101, HCDR2 of SEQ ID NO: 102, HCDR3 of SEQ ID NO: 189, LCDR1 of SEQ ID NO: 105, LCDR2 of SEQ ID NO: 197, and LCDR3 of SEQ ID NO: 107.

[0408] In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a CDR differing from one or more amino acids in the CDRs shown in Table E. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a CDR differing from any of the CDRs shown in Table E by no more than 5 amino acids. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a CDR differing from any of the CDRs shown in Table E by no more than 4 amino acids. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a CDR differing from any of the CDRs shown in Table E by no more than 3 amino acids. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a CDR differing from any of the CDRs shown in Table E by no more than 2 amino acids. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a CDR differing from any of the CDRs shown in Table E by no more than 1 amino acid.

[0409] In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises: HCDR1 containing an amino acid sequence that differs from GYSFTRYW (SEQ ID NO: 101) by no more than 2 amino acids; HCDR2 containing an amino acid sequence that differs from IDPSDSET (SEQ ID NO: 102) by no more than 1 amino acid; HCDR3 containing an amino acid sequence that differs from ARGGYFGREWYYDV (SEQ ID NO: 103) by no more than 4 amino acids; LCDR1 containing an amino acid sequence that differs from QSLVHRNGNTY (SEQ ID NO: 105) by no more than 2 amino acids; LCDR2 containing an amino acid sequence that differs from EVS (SEQ ID NO: 106) by no more than 1 amino acid; and LCDR3 containing an amino acid sequence that differs from SQSTHVPWT (SEQ ID NO: 75, LCDR3G) by no more than 4 amino acids.

[0410] In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises: HCDR1 containing an amino acid sequence that differs from GYSFTRYW (SEQ ID NO: 101) by no more than 2 amino acids; HCDR2 containing an amino acid sequence that differs from IDPSDSET (SEQ ID NO: 102) by no more than 1 amino acid; HCDR3 containing an amino acid sequence that differs from ARGGYFGEEWYHDV (SEQ ID NO: 104) by no more than 4 amino acids; LCDR1 containing an amino acid sequence that differs from QSLVHRNGNTY (SEQ ID NO: 105) by no more than 2 amino acids; LCDR2 containing an amino acid sequence that differs from EVS (SEQ ID No: 106) by no more than 1 amino acid; and LCDR3 containing an amino acid sequence that differs from AQSTQLPYT (SEQ ID NO: 107) by no more than 4 amino acids.

[0411] In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises: HCDR1 containing an amino acid sequence that differs from SEQ ID NO: 101 by no more than 2 amino acids; HCDR2 containing an amino acid sequence that differs from SEQ ID NO: 102 by no more than 1 amino acid; HCDR3 containing an amino acid sequence that differs from SEQ ID NO: 188 by no more than 4 amino acids; LCDR1 containing an amino acid sequence that differs from SEQ ID NO: 105 by no more than 2 amino acids; LCDR2 containing an amino acid sequence that differs from SEQ ID NO: 106 by no more than 1 amino acid; and LCDR3 containing an amino acid sequence that differs from SEQ ID NO: 198 by no more than 4 amino acids.

[0412] In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises: HCDR1 containing an amino acid sequence that differs from SEQ ID NO: 101 by no more than 2 amino acids; HCDR2 containing an amino acid sequence that differs from SEQ ID NO: 102 by no more than 1 amino acid; HCDR3 containing an amino acid sequence that differs from SEQ ID NO: 189 by no more than 4 amino acids; LCDR1 containing an amino acid sequence that differs from SEQ ID NO: 105 by no more than 2 amino acids; LCDR2 containing an amino acid sequence that differs from SEQ ID NO: 106 by no more than 1 amino acid; and LCDR3 containing an amino acid sequence that differs from SEQ ID NO: 75 by no more than 4 amino acids.

[0413] In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises: HCDR1 containing an amino acid sequence that differs from SEQ ID NO: 101 by no more than 2 amino acids; HCDR2 containing an amino acid sequence that differs from SEQ ID NO: 102 by no more than 1 amino acid; HCDR3 containing an amino acid sequence that differs from SEQ ID NO: 190 by no more than 4 amino acids; LCDR1 containing an amino acid sequence that differs from SEQ ID NO: 105 by no more than 2 amino acids; LCDR2 containing an amino acid sequence that differs from SEQ ID NO: 106 by no more than 1 amino acid; and LCDR3 containing an amino acid sequence that differs from SEQ ID NO: 75 by no more than 4 amino acids.

[0414] In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises: HCDR1 containing an amino acid sequence that differs from SEQ ID NO: 101 by no more than 2 amino acids; HCDR2 containing an amino acid sequence that differs from SEQ ID NO: 102 by no more than 1 amino acid; HCDR3 containing an amino acid sequence that differs from SEQ ID NO: 191 by no more than 4 amino acids; LCDR1 containing an amino acid sequence that differs from SEQ ID NO: 105 by no more than 2 amino acids; LCDR2 containing an amino acid sequence that differs from SEQ ID NO: 106 by no more than 1 amino acid; and LCDR3 containing an amino acid sequence that differs from SEQ ID NO: 75 by no more than 4 amino acids.

[0415] In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises: HCDR1 containing an amino acid sequence that differs from SEQ ID NO: 101 by no more than 2 amino acids; HCDR2 containing an amino acid sequence that differs from SEQ ID NO: 102 by no more than 1 amino acid; HCDR3 containing an amino acid sequence that differs from SEQ ID NO: 192 by no more than 4 amino acids; LCDR1 containing an amino acid sequence that differs from SEQ ID NO: 105 by no more than 2 amino acids; LCDR2 containing an amino acid sequence that differs from SEQ ID NO: 106 by no more than 1 amino acid; and LCDR3 containing an amino acid sequence that differs from SEQ ID NO: 75 by no more than 4 amino acids.

[0416] In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises: HCDR1 containing an amino acid sequence that differs from SEQ ID NO: 101 by no more than 2 amino acids; HCDR2 containing an amino acid sequence that differs from SEQ ID NO: 102 by no more than 1 amino acid; HCDR3 containing an amino acid sequence that differs from SEQ ID NO: 193 by no more than 4 amino acids; LCDR1 containing an amino acid sequence that differs from SEQ ID NO: 105 by no more than 2 amino acids; LCDR2 containing an amino acid sequence that differs from SEQ ID NO: 106 by no more than 1 amino acid; and LCDR3 containing an amino acid sequence that differs from SEQ ID NO: 198 by no more than 4 amino acids.

[0417] In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises: HCDR1 containing an amino acid sequence that differs from SEQ ID NO: 101 by no more than 2 amino acids; HCDR2 containing an amino acid sequence that differs from SEQ ID NO: 102 by no more than 1 amino acid; HCDR3 containing an amino acid sequence that differs from SEQ ID NO: 194 by no more than 4 amino acids; LCDR1 containing an amino acid sequence that differs from SEQ ID NO: 105 by no more than 2 amino acids; LCDR2 containing an amino acid sequence that differs from SEQ ID NO: 106 by no more than 1 amino acid; and LCDR3 containing an amino acid sequence that differs from SEQ ID NO: 107 by no more than 4 amino acids.

[0418] In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises: HCDR1 containing an amino acid sequence that differs from SEQ ID NO: 101 by no more than 2 amino acids; HCDR2 containing an amino acid sequence that differs from SEQ ID NO: 102 by no more than 1 amino acid; HCDR3 containing an amino acid sequence that differs from SEQ ID NO: 194 by no more than 4 amino acids; LCDR1 containing an amino acid sequence that differs from SEQ ID NO: 105 by no more than 2 amino acids; LCDR2 containing an amino acid sequence that differs from SEQ ID NO: 196 by no more than 1 amino acid; and LCDR3 containing an amino acid sequence that differs from SEQ ID NO: 107 by no more than 4 amino acids.

[0419] In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises: HCDR1 containing an amino acid sequence that differs from SEQ ID NO: 101 by no more than 2 amino acids; HCDR2 containing an amino acid sequence that differs from SEQ ID NO: 102 by no more than 1 amino acid; HCDR3 containing an amino acid sequence that differs from SEQ ID NO: 195 by no more than 4 amino acids; LCDR1 containing an amino acid sequence that differs from SEQ ID NO: 105 by no more than 2 amino acids; LCDR2 containing an amino acid sequence that differs from SEQ ID NO: 63 by no more than 1 amino acid; and LCDR3 containing an amino acid sequence that differs from SEQ ID NO: 75 by no more than 4 amino acids.

[0420] In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises: HCDR1 containing an amino acid sequence that differs from SEQ ID NO: 101 by no more than 2 amino acids; HCDR2 containing an amino acid sequence that differs from SEQ ID NO: 102 by no more than 1 amino acid; HCDR3 containing an amino acid sequence that differs from SEQ ID NO: 104 by no more than 4 amino acids; LCDR1 containing an amino acid sequence that differs from SEQ ID NO: 105 by no more than 2 amino acids; LCDR2 containing an amino acid sequence that differs from SEQ ID NO: 63 by no more than 1 amino acid; and LCDR3 containing an amino acid sequence that differs from SEQ ID NO: 75 by no more than 4 amino acids.

[0421] In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises: HCDR1 containing an amino acid sequence that differs from SEQ ID NO: 101 by no more than 2 amino acids; HCDR2 containing an amino acid sequence that differs from SEQ ID NO: 102 by no more than 1 amino acid; HCDR3 containing an amino acid sequence that differs from SEQ ID NO: 104 by no more than 4 amino acids; LCDR1 containing an amino acid sequence that differs from SEQ ID NO: 105 by no more than 2 amino acids; LCDR2 containing an amino acid sequence that differs from SEQ ID NO: 197 by no more than 1 amino acid; and LCDR3 containing an amino acid sequence that differs from SEQ ID NO: 75 by no more than 4 amino acids.

[0422] In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises: HCDR1 containing an amino acid sequence that differs from SEQ ID NO: 101 by no more than 2 amino acids; HCDR2 containing an amino acid sequence that differs from SEQ ID NO: 102 by no more than 1 amino acid; HCDR3 containing an amino acid sequence that differs from SEQ ID NO: 190 by no more than 4 amino acids; LCDR1 containing an amino acid sequence that differs from SEQ ID NO: 105 by no more than 2 amino acids; LCDR2 containing an amino acid sequence that differs from SEQ ID NO: 106 by no more than 1 amino acid; and LCDR3 containing an amino acid sequence that differs from SEQ ID NO: 198 by no more than 4 amino acids.

[0423] In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises: HCDR1 containing an amino acid sequence that differs from SEQ ID NO: 101 by no more than 2 amino acids; HCDR2 containing an amino acid sequence that differs from SEQ ID NO: 102 by no more than 1 amino acid; HCDR3 containing an amino acid sequence that differs from SEQ ID NO: 189 by no more than 4 amino acids; LCDR1 containing an amino acid sequence that differs from SEQ ID NO: 105 by no more than 2 amino acids; LCDR2 containing an amino acid sequence that differs from SEQ ID NO: 197 by no more than 1 amino acid; and LCDR3 containing an amino acid sequence that differs from SEQ ID NO: 107 by no more than 4 amino acids.

[0424] Table F. Exemplary VH and VL sequences of humanized anti-α7β1 integrin antibodies .

[0425]

[0426]

[0427]

[0428] In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 80% of the same amino acid sequence as SEQ ID NO:186. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 83% of the same amino acid sequence as SEQ ID NO:186. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 85% of the same amino acid sequence as SEQ ID NO:186. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 87% of the same amino acid sequence as SEQ ID NO:186. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 90% of the same amino acid sequence as SEQ ID NO:186. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 92% of the same amino acid sequence as SEQ ID NO:186. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 93% of the same amino acid sequence as SEQ ID NO: 186. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 94% of the same amino acid sequence as SEQ ID NO: 186. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 95% of the same amino acid sequence as SEQ ID NO: 186. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 97% of the same amino acid sequence as SEQ ID NO: 186. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 98% of the same amino acid sequence as SEQ ID NO: 186. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 99% of the same amino acid sequence as SEQ ID NO: 186. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment contains a variable heavy region having the same amino acid sequence as SEQ ID NO: 186.

[0429] In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 80% of the same amino acid sequence as SEQ ID NO: 108. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 83% of the same amino acid sequence as SEQ ID NO: 108. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 85% of the same amino acid sequence as SEQ ID NO: 108. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 87% of the same amino acid sequence as SEQ ID NO: 108. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 90% of the same amino acid sequence as SEQ ID NO: 108. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 92% of the same amino acid sequence as SEQ ID NO: 108. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 93% of the same amino acid sequence as SEQ ID NO: 108. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 94% of the same amino acid sequence as SEQ ID NO: 108. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 95% of the same amino acid sequence as SEQ ID NO: 108. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 97% of the same amino acid sequence as SEQ ID NO: 108. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 98% of the same amino acid sequence as SEQ ID NO: 108. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 99% of the same amino acid sequence as SEQ ID NO: 108. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment contains a variable heavy region having the same amino acid sequence as SEQ ID NO: 108.

[0430] In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 80% of the same amino acid sequence as SEQ ID NO: 110. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 83% of the same amino acid sequence as SEQ ID NO: 110. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 85% of the same amino acid sequence as SEQ ID NO: 110. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 87% of the same amino acid sequence as SEQ ID NO: 110. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 90% of the same amino acid sequence as SEQ ID NO: 110. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 92% of the same amino acid sequence as SEQ ID NO: 110. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 93% of the same amino acid sequence as SEQ ID NO: 110. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 94% of the same amino acid sequence as SEQ ID NO: 110. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 95% of the same amino acid sequence as SEQ ID NO: 110. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 97% of the same amino acid sequence as SEQ ID NO: 110. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 98% of the same amino acid sequence as SEQ ID NO: 110. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 99% of the same amino acid sequence as SEQ ID NO: 110. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment contains a variable heavy region having the same amino acid sequence as SEQ ID NO: 110.

[0431] In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 80% of the same amino acid sequence as SEQ ID NO:199. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 83% of the same amino acid sequence as SEQ ID NO:199. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 85% of the same amino acid sequence as SEQ ID NO:199. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 87% of the same amino acid sequence as SEQ ID NO:199. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 90% of the same amino acid sequence as SEQ ID NO:199. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 92% of the same amino acid sequence as SEQ ID NO:199. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 93% of the same amino acid sequence as SEQ ID NO: 199. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 94% of the same amino acid sequence as SEQ ID NO: 199. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 95% of the same amino acid sequence as SEQ ID NO: 199. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 97% of the same amino acid sequence as SEQ ID NO: 199. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 98% of the same amino acid sequence as SEQ ID NO: 199. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 99% of the same amino acid sequence as SEQ ID NO: 199. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment contains a variable heavy region having the same amino acid sequence as SEQ ID NO: 199.

[0432] In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 80% of the same amino acid sequence as SEQ ID NO:201. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 83% of the same amino acid sequence as SEQ ID NO:201. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 85% of the same amino acid sequence as SEQ ID NO:201. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 87% of the same amino acid sequence as SEQ ID NO:201. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 90% of the same amino acid sequence as SEQ ID NO:201. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 92% of the same amino acid sequence as SEQ ID NO:201. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 93% of the same amino acid sequence as SEQ ID NO: 201. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 94% of the same amino acid sequence as SEQ ID NO: 201. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 95% of the same amino acid sequence as SEQ ID NO: 201. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 97% of the same amino acid sequence as SEQ ID NO: 201. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 98% of the same amino acid sequence as SEQ ID NO: 201. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 99% of the same amino acid sequence as SEQ ID NO: 201. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment contains a variable heavy region having the same amino acid sequence as SEQ ID NO: 201.

[0433] In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 80% of the same amino acid sequence as SEQ ID NO:203. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 83% of the same amino acid sequence as SEQ ID NO:203. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 85% of the same amino acid sequence as SEQ ID NO:203. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 87% of the same amino acid sequence as SEQ ID NO:203. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 90% of the same amino acid sequence as SEQ ID NO:203. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 92% of the same amino acid sequence as SEQ ID NO:203. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 93% of the same amino acid sequence as SEQ ID NO: 203. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 94% of the same amino acid sequence as SEQ ID NO: 203. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 95% of the same amino acid sequence as SEQ ID NO: 203. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 97% of the same amino acid sequence as SEQ ID NO: 203. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 98% of the same amino acid sequence as SEQ ID NO: 203. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 99% of the same amino acid sequence as SEQ ID NO: 203. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment contains a variable heavy region having the same amino acid sequence as SEQ ID NO: 203.

[0434] In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 80% of the same amino acid sequence as SEQ ID NO:205. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 83% of the same amino acid sequence as SEQ ID NO:205. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 85% of the same amino acid sequence as SEQ ID NO:205. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 87% of the same amino acid sequence as SEQ ID NO:205. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 90% of the same amino acid sequence as SEQ ID NO:205. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 92% of the same amino acid sequence as SEQ ID NO:205. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 93% of the same amino acid sequence as SEQ ID NO: 205. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 94% of the same amino acid sequence as SEQ ID NO: 205. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 95% of the same amino acid sequence as SEQ ID NO: 205. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 97% of the same amino acid sequence as SEQ ID NO: 205. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 98% of the same amino acid sequence as SEQ ID NO: 205. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 99% of the same amino acid sequence as SEQ ID NO: 205. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment contains a variable heavy region having the same amino acid sequence as SEQ ID NO: 205.

[0435] In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 80% of the same amino acid sequence as SEQ ID NO:207. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 83% of the same amino acid sequence as SEQ ID NO:207. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 85% of the same amino acid sequence as SEQ ID NO:207. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 87% of the same amino acid sequence as SEQ ID NO:207. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 90% of the same amino acid sequence as SEQ ID NO:207. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 92% of the same amino acid sequence as SEQ ID NO:207. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 93% of the same amino acid sequence as SEQ ID NO: 207. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 94% of the same amino acid sequence as SEQ ID NO: 207. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 95% of the same amino acid sequence as SEQ ID NO: 207. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 97% of the same amino acid sequence as SEQ ID NO: 207. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 98% of the same amino acid sequence as SEQ ID NO: 207. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 99% of the same amino acid sequence as SEQ ID NO: 207. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment contains a variable heavy region having the same amino acid sequence as SEQ ID NO: 207.

[0436] In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 80% of the same amino acid sequence as SEQ ID NO:209. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 83% of the same amino acid sequence as SEQ ID NO:209. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 85% of the same amino acid sequence as SEQ ID NO:209. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 87% of the same amino acid sequence as SEQ ID NO:209. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 90% of the same amino acid sequence as SEQ ID NO:209. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 92% of the same amino acid sequence as SEQ ID NO:209. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 93% of the same amino acid sequence as SEQ ID NO: 9. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 94% of the same amino acid sequence as SEQ ID NO: 209. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 95% of the same amino acid sequence as SEQ ID NO: 209. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 97% of the same amino acid sequence as SEQ ID NO: 209. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 98% of the same amino acid sequence as SEQ ID NO: 209. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 99% of the same amino acid sequence as SEQ ID NO: 209. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment contains a variable heavy region having the same amino acid sequence as SEQ ID NO: 209.

[0437] In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 80% of the same amino acid sequence as SEQ ID NO:211. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 83% of the same amino acid sequence as SEQ ID NO:211. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 85% of the same amino acid sequence as SEQ ID NO:211. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 87% of the same amino acid sequence as SEQ ID NO:211. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 90% of the same amino acid sequence as SEQ ID NO:211. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 92% of the same amino acid sequence as SEQ ID NO:211. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 93% of the same amino acid sequence as SEQ ID NO: 211. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 94% of the same amino acid sequence as SEQ ID NO: 211. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 95% of the same amino acid sequence as SEQ ID NO: 211. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 97% of the same amino acid sequence as SEQ ID NO: 211. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 98% of the same amino acid sequence as SEQ ID NO: 211. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 99% of the same amino acid sequence as SEQ ID NO: 211. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment contains a variable heavy region having the same amino acid sequence as SEQ ID NO: 211.

[0438] In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 80% of the same amino acid sequence as SEQ ID NO:213. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 83% of the same amino acid sequence as SEQ ID NO:213. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 85% of the same amino acid sequence as SEQ ID NO:213. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 87% of the same amino acid sequence as SEQ ID NO:213. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 90% of the same amino acid sequence as SEQ ID NO:213. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 92% of the same amino acid sequence as SEQ ID NO:213. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 93% of the same amino acid sequence as SEQ ID NO: 213. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 94% of the same amino acid sequence as SEQ ID NO: 213. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 95% of the same amino acid sequence as SEQ ID NO: 213. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 97% of the same amino acid sequence as SEQ ID NO: 213. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 98% of the same amino acid sequence as SEQ ID NO: 213. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 99% of the same amino acid sequence as SEQ ID NO: 213. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment contains a variable heavy region having the same amino acid sequence as SEQ ID NO: 213.

[0439] In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 80% of the same amino acid sequence as SEQ ID NO:215. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 83% of the same amino acid sequence as SEQ ID NO:215. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 85% of the same amino acid sequence as SEQ ID NO:215. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 87% of the same amino acid sequence as SEQ ID NO:215. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 90% of the same amino acid sequence as SEQ ID NO:215. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 92% of the same amino acid sequence as SEQ ID NO:215. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 93% of the same amino acid sequence as SEQ ID NO: 215. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 94% of the same amino acid sequence as SEQ ID NO: 215. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 95% of the same amino acid sequence as SEQ ID NO: 215. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 97% of the same amino acid sequence as SEQ ID NO: 215. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 98% of the same amino acid sequence as SEQ ID NO: 215. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 99% of the same amino acid sequence as SEQ ID NO: 215. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment contains a variable heavy region having the same amino acid sequence as SEQ ID NO: 215.

[0440] In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 80% of the same amino acid sequence as SEQ ID NO:217. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 83% of the same amino acid sequence as SEQ ID NO:217. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 85% of the same amino acid sequence as SEQ ID NO:217. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 87% of the same amino acid sequence as SEQ ID NO:217. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 90% of the same amino acid sequence as SEQ ID NO:217. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 92% of the same amino acid sequence as SEQ ID NO:217. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 93% of the same amino acid sequence as SEQ ID NO: 217. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 94% of the same amino acid sequence as SEQ ID NO: 217. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 95% of the same amino acid sequence as SEQ ID NO: 217. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 97% of the same amino acid sequence as SEQ ID NO: 217. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 98% of the same amino acid sequence as SEQ ID NO: 217. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 99% of the same amino acid sequence as SEQ ID NO: 217. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment contains a variable heavy region having the same amino acid sequence as SEQ ID NO: 217.

[0441] In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 80% of the same amino acid sequence as SEQ ID NO:219. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 83% of the same amino acid sequence as SEQ ID NO:219. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 85% of the same amino acid sequence as SEQ ID NO:219. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 87% of the same amino acid sequence as SEQ ID NO:219. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 90% of the same amino acid sequence as SEQ ID NO:219. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 92% of the same amino acid sequence as SEQ ID NO:219. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 93% of the same amino acid sequence as SEQ ID NO: 219. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 94% of the same amino acid sequence as SEQ ID NO: 219. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 95% of the same amino acid sequence as SEQ ID NO: 219. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 97% of the same amino acid sequence as SEQ ID NO: 219. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 98% of the same amino acid sequence as SEQ ID NO: 219. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 99% of the same amino acid sequence as SEQ ID NO: 219. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment contains a variable heavy region having the same amino acid sequence as SEQ ID NO: 219.

[0442] In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 80% of the same amino acid sequence as SEQ ID NO:221. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 83% of the same amino acid sequence as SEQ ID NO:221. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 85% of the same amino acid sequence as SEQ ID NO:221. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 87% of the same amino acid sequence as SEQ ID NO:221. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 90% of the same amino acid sequence as SEQ ID NO:221. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 92% of the same amino acid sequence as SEQ ID NO:221. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 93% of the same amino acid sequence as SEQ ID NO: 221. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 94% of the same amino acid sequence as SEQ ID NO: 221. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 95% of the same amino acid sequence as SEQ ID NO: 221. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 97% of the same amino acid sequence as SEQ ID NO: 221. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 98% of the same amino acid sequence as SEQ ID NO: 221. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 99% of the same amino acid sequence as SEQ ID NO: 221. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment contains a variable heavy region having the same amino acid sequence as SEQ ID NO: 221.

[0443] In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 80% of the same amino acid sequence as SEQ ID NO:223. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 83% of the same amino acid sequence as SEQ ID NO:223. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 85% of the same amino acid sequence as SEQ ID NO:223. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 87% of the same amino acid sequence as SEQ ID NO:223. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 90% of the same amino acid sequence as SEQ ID NO:223. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 92% of the same amino acid sequence as SEQ ID NO:223. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 93% of the same amino acid sequence as SEQ ID NO: 223. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 94% of the same amino acid sequence as SEQ ID NO: 223. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 95% of the same amino acid sequence as SEQ ID NO: 223. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 97% of the same amino acid sequence as SEQ ID NO: 223. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 98% of the same amino acid sequence as SEQ ID NO: 223. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable heavy region containing at least 99% of the same amino acid sequence as SEQ ID NO: 223. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment contains a variable heavy region having the same amino acid sequence as SEQ ID NO: 223.

[0444] In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region containing at least 80% of the same amino acid sequence as SEQ ID NO:187. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region containing at least 83% of the same amino acid sequence as SEQ ID NO:187. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region containing at least 85% of the same amino acid sequence as SEQ ID NO:187. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region containing at least 87% of the same amino acid sequence as SEQ ID NO:187. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region containing at least 90% of the same amino acid sequence as SEQ ID NO:187. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region containing at least 92% of the same amino acid sequence as SEQ ID NO:187. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region containing at least 93% of the same amino acid sequence as SEQ ID NO: 187. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region containing at least 94% of the same amino acid sequence as SEQ ID NO: 187. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region containing at least 95% of the same amino acid sequence as SEQ ID NO: 187. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region containing at least 97% of the same amino acid sequence as SEQ ID NO: 187. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region containing at least 98% of the same amino acid sequence as SEQ ID NO: 187. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region containing at least 99% of the same amino acid sequence as SEQ ID NO: 187. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment contains a variable light region having the same amino acid sequence as SEQ ID NO: 187.

[0445] In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region containing at least 80% of the same amino acid sequence as SEQ ID NO: 109. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region containing at least 83% of the same amino acid sequence as SEQ ID NO: 109. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region containing at least 85% of the same amino acid sequence as SEQ ID NO: 109. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region containing at least 87% of the same amino acid sequence as SEQ ID NO: 109. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region containing at least 90% of the same amino acid sequence as SEQ ID NO: 109. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region containing at least 92% of the same amino acid sequence as SEQ ID NO: 109. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region containing at least 93% of the same amino acid sequence as SEQ ID NO: 109. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region containing at least 94% of the same amino acid sequence as SEQ ID NO: 109. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region containing at least 95% of the same amino acid sequence as SEQ ID NO: 109. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region containing at least 97% of the same amino acid sequence as SEQ ID NO: 109. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region containing at least 98% of the same amino acid sequence as SEQ ID NO: 109. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region containing at least 99% of the same amino acid sequence as SEQ ID NO: 109. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment contains a variable light region having the same amino acid sequence as SEQ ID NO: 109.

[0446] In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region containing at least 80% of the same amino acid sequence as SEQ ID NO: 111. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region containing at least 83% of the same amino acid sequence as SEQ ID NO: 111. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region containing at least 85% of the same amino acid sequence as SEQ ID NO: 111. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region containing at least 87% of the same amino acid sequence as SEQ ID NO: 111. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region containing at least 90% of the same amino acid sequence as SEQ ID NO: 111. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region containing at least 92% of the same amino acid sequence as SEQ ID NO: 111. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region containing at least 93% of the same amino acid sequence as SEQ ID NO: 111. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region containing at least 94% of the same amino acid sequence as SEQ ID NO: 111. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region containing at least 95% of the same amino acid sequence as SEQ ID NO: 111. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region containing at least 97% of the same amino acid sequence as SEQ ID NO: 111. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region containing at least 98% of the same amino acid sequence as SEQ ID NO: 111. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region containing at least 99% of the same amino acid sequence as SEQ ID NO: 111. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment contains a variable light region having the same amino acid sequence as SEQ ID NO: 111.

[0447] In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region containing at least 80% of the same amino acid sequence as SEQ ID NO:200. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region containing at least 83% of the same amino acid sequence as SEQ ID NO:200. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region containing at least 85% of the same amino acid sequence as SEQ ID NO:200. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region containing at least 87% of the same amino acid sequence as SEQ ID NO:200. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region containing at least 90% of the same amino acid sequence as SEQ ID NO:200. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region containing at least 92% of the same amino acid sequence as SEQ ID NO:200. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region containing at least 93% of the same amino acid sequence as SEQ ID NO: 200. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a variable light region containing at least 94% of the same amino acid sequence as SEQ ID NO: 200. In some embodiments, the integrin α7β1 antibody or its antigen-binding fragment comprises a v...

Claims

1. An antibody or antigen-binding fragment that binds to the calf-2 domain of the α7β1 integrin but does not compete with a 20TFT antibody, wherein the antibody stabilizes the extended conformation of the α7β1 integrin.

2. An antibody or antigen-binding fragment that binds to α7β1 integrin and competes with a reference antibody for binding to α7β1 integrin. The reference antibody comprises HCDR1 with sequence GFTFSSYT (SEQ ID NO: 2), HCDR2 with sequence ISIVGNYI (SEQ ID NO: 16), HCDR3 with sequence ARRKWEHDAFDI (SEQ ID NO: 32), LCDR1 with sequence SLRSYY (SEQ ID NO: 47), LCDR2 with sequence GKN (SEQ ID NO: 59), and LCDR3 with sequence TSRDNSGNHVV (SEQ ID NO: 70).

3. An antibody or antigen-binding fragment that binds to α7β1 integrin, said antibody or antigen-binding fragment comprising: (a) A functional unit for stabilizing the extended conformation of the α7β1 integrin; and optionally, (b) Fc structural domain.

4. An antibody or antigen-binding fragment that binds to α7β1 integrin, wherein the antibody binds to a region comprising the amino acid sequence of integrin α7 at positions 856-862, 867-889, 1011-1017, 897-905, or 1002-1010, wherein the antibody stabilizes the extended conformation of α7β1 integrin.

5. An antibody or antigen-binding fragment that binds to the calf-1 domain of the α7β1 integrin, wherein the antibody stabilizes the extended conformation of the α7β1 integrin.

6. An antibody or antigen-binding fragment that binds to α7β1 integrin and competes with a reference antibody for binding to α7β1 integrin, wherein the reference antibody comprises HCDR1 of sequence GYSFTRYW (SEQ ID NO: 7), HCDR2 of sequence IDPSDSET (SEQ ID NO: 22), HCDR3 of sequence ARGGYFGEGWYFDV (SEQ ID NO: 38), LCDR1 of sequence QSLVHRNGNTY (SEQ ID NO: 51), LCDR2 of sequence KVS (SEQ ID NO: 63), and LCDR3 of sequence SQSTHVPWT (SEQ ID NO: 75).

7. An antibody or antigen-binding fragment that binds to α7β1 integrin and competes with a reference antibody for binding to α7β1 integrin. The reference antibody comprises HCDR1 of sequence GFSLTSYG (SEQ ID NO: 9), HCDR2 of sequence IWVGGIT (SEQ ID NO: 24), HCDR3 of sequence ARDGYYGDFDV (SEQ ID NO: 40), LCDR1 of sequence QDINKF (SEQ ID NO: 53), LCDR2 of sequence YTS (SEQ ID NO: 65), and LCDR3 of sequence LQYDNLRT (SEQ ID NO: 77).

8. An antibody or antigen-binding fragment that binds to α7β1 integrin, said antibody or antigen-binding fragment comprising: (a) A functional unit for binding to the calf-1 domain of the α7β1 integrin; and (b) Fc structural domain.

9. An antibody or antigen-binding fragment that binds to α7β1 integrin, wherein the antibody binds to a region comprising the amino acid sequence of integrin α7 at positions 771-778, 793-805, wherein the antibody stabilizes the extended conformation of α7β1 integrin.

10. The antibody or antigen-binding fragment according to claim 9, wherein the region comprises amino acids R771, A772, L773, D774, P775, A776, E777, K778, E793, L794, G795, N796, P797, M798, K799, R800, G801, A802, Q803, V804 and / or T805.

11. An antibody or antigen-binding fragment that binds to α7β1 integrin, wherein the antibody comprises: HCDR1 of sequence GFTFSSYT (SEQ ID NO: 2), HCDR2 of sequence ISIVGNYI (SEQ ID NO: 16), and HCDR3 of sequence ARRKWEHDAFDI (SEQ ID NO: 32); and LCDR1 with sequence SLRSYY (SEQ ID NO: 47), LCDR2 with sequence GKN (SEQ ID NO: 59), and LCDR3 with sequence TSRDNSGNHVV (SEQ ID NO: 70).

12. An antibody or antigen-binding fragment that binds to α7β1 integrin, wherein the antibody comprises: HCDR1 of sequence GYTFTGYY (SEQ ID NO: 1), HCDR2 of sequence INPNSGGT (SEQ ID NO: 15), and HCDR3 of sequence AREGANWDYYYYGMDV (SEQ ID NO: 31); and LCDR1 of sequence SSNIGSKT (SEQ ID NO: 46), LCDR2 of sequence SNN (SEQ ID NO: 58), and LCDR3 of sequence AAWDDSLNGPV (SEQ ID NO: 69).

13. An antibody or antigen-binding fragment that binds to α7β1 integrin, wherein the antibody comprises: HCDR1 of sequence GFTFSSYS (SEQ ID NO: 3), HCDR2 of sequence ISTSSSYI (SEQ ID NO: 17), and HCDR3 of sequence ARRAWESDAFAI (SEQ ID NO: 33); and LCDR1 with sequence SLRSYY (SEQ ID NO: 47), LCDR2 with sequence GKN (SEQ ID NO: 59), and LCDR3 with sequence NSRDSSGNHVV (SEQ ID NO: 71).

14. An antibody or antigen-binding fragment that binds to α7β1 integrin, wherein the antibody comprises: HCDR1 of sequence GFTFSSYA (SEQ ID NO: 4), HCDR2 of sequence ISDSGGIA (SEQ ID NO: 18), and HCDR3 of sequence VRDGY (SEQ ID NO: 34); and LCDR1 of sequence QSLLDSDDGYTY (SEQ ID NO: 48), LCDR2 of sequence TLS (SEQ ID NO: 60), and LCDR3 of sequence MQRIEFPLT (SEQ ID NO: 72).

15. An antibody or antigen-binding fragment that binds to α7β1 integrin, wherein the antibody comprises: HCDR1 of sequence GFTFSSYA (SEQ ID NO: 4), HCDR2 of sequence IHYSGGTT (SEQ ID NO: 19), and HCDR3 of sequence VKDGY (SEQ ID NO: 35); and LCDR1 of sequence QSLLDSDDGYTY (SEQ ID NO: 48), LCDR2 of sequence TLS (SEQ ID NO: 60), and LCDR3 of sequence MQRIEFPLT (SEQ ID NO: 72).

16. An antibody or antigen-binding fragment that binds to α7β1 integrin, wherein the antibody comprises: HCDR1 of sequence GFTFSRFW (SEQ ID NO: 5), HCDR2 of sequence TKQDGSEK (SEQ ID NO: 20), and HCDR3 of sequence AREGSGAYWAFDI (SEQ ID NO: 36); and LCDR1 with sequence QSLVHNDGNTY (SEQ ID NO: 49), LCDR2 with sequence KIS (SEQ ID NO: 61), and LCDR3 with sequence LQATQFPLT (SEQ ID NO: 73).

17. An antibody or antigen-binding fragment that binds to α7β1 integrin, wherein the antibody comprises: HCDR1 of sequence GGSISSYY (SEQ ID NO: 6), HCDR2 of sequence IYTRGST (SEQ ID NO: 21), and HCDR3 of sequence ARVFGGNYRFDAFHI (SEQ ID NO: 37); and LCDR1 of sequence SSNIGAGYD (SEQ ID NO: 50), LCDR2 of sequence GNN (SEQ ID NO: 62), and LCDR3 of sequence QSYDSSLSGYV (SEQ ID NO: 74).

18. An antibody or antigen-binding fragment that binds to α7β1 integrin, wherein the antibody comprises: HCDR1 of sequence GYSFTRYW (SEQ ID NO: 7), HCDR2 of sequence IDPSDSET (SEQ ID NO: 22), and HCDR3 of sequence ARGGYFGEGWYFDV (SEQ ID NO: 38); and LCDR1 with sequence QSLVHRNGNTY (SEQ ID NO: 51), LCDR2 with sequence KVS (SEQ ID NO: 63), and LCDR3 with sequence SQSTHVPWT (SEQ ID NO: 75).

19. An antibody or antigen-binding fragment that binds to α7β1 integrin, wherein the antibody comprises: HCDR1 of sequence GYTFTSYW (SEQ ID NO: 8), HCDR2 of sequence IYPSDSYT (SEQ ID NO: 23), and HCDR3 of sequence TRRANYVGAMDY (SEQ ID NO: 39); and LCDR1 with sequence SVSY (SEQ ID NO: 52), LCDR2 with sequence ATS (SEQ ID NO: 64), and LCDR3 with sequence QQWSSNPLT (SEQ ID NO: 76).

20. An antibody or antigen-binding fragment that binds to α7β1 integrin, wherein the antibody comprises: HCDR1 of sequence GFSLTSYG (SEQ ID NO: 9), HCDR2 of sequence IWVGGIT (SEQ ID NO: 24), and HCDR3 of sequence ARDGYYGDFDV (SEQ ID NO: 40); and LCDR1 with sequence QDINKF (SEQ ID NO: 53), LCDR2 with sequence YTS (SEQ ID NO: 65), and LCDR3 with sequence LQYDNLRT (SEQ ID NO: 77).

21. An antibody or antigen-binding fragment that binds to α7β1 integrin, wherein the antibody comprises: The HCDR1 of sequence GFSLTSYG (SEQ ID NO: 9), the HCDR2 of sequence IWAGGIT (SEQ ID NO: 25), and the ARDGYYGDFDV sequence HCDR3 of (SEQ ID NO: 40); and LCDR1 with sequence QDINKY (SEQ ID NO: 54), LCDR2 with sequence YTS (SEQ ID NO: 65), and LCDR3 with sequence LQYDNLRT (SEQ ID NO: 77).

22. An antibody or antigen-binding fragment that binds to α7β1 integrin, wherein the antibody comprises: HCDR1 of sequence GFSLTSYG (SEQ ID NO: 9), HCDR2 of sequence IWAGGIT (SEQ ID NO: 25), and HCDR3 of sequence ARDGYYGHFDV (SEQ ID NO: 41); and LCDR1 with sequence QDINKY (SEQ ID NO: 54), LCDR2 with sequence YTS (SEQ ID NO: 65), and LCDR3 with sequence LQYDNLRA (SEQ ID NO: 78).

23. An antibody or antigen-binding fragment that binds to α7β1 integrin, wherein the antibody comprises: HCDR1 of sequence GFTFSSDA (SEQ ID NO: 10), HCDR2 of sequence ISIGGSA (SEQ ID NO: 26), and HCDR3 of sequence ARGGDYDAMDY (SEQ ID NO: 178); and LCDR1 with sequence QSISDL (SEQ ID NO: 55), LCDR2 with sequence YAS (SEQ ID NO: 66), and LCDR3 with sequence QNGHNFPFT (SEQ ID NO: 79).

24. An antibody or antigen-binding fragment that binds to α7β1 integrin, wherein the antibody comprises: HCDR1 of sequence GFTFSSSA (SEQ ID NO: 11), HCDR2 of sequence ISVGGST (SEQ ID NO: 27), and HCDR3 of sequence ARGGDYDAMDY (SEQ ID NO: 42); and LCDR1 with sequence QSISDY (SEQ ID NO: 56), LCDR2 with sequence YAS (SEQ ID NO: 66), and LCDR3 with sequence QNGHSFPFT (SEQ ID NO: 80).

25. An antibody or antigen-binding fragment that binds to α7β1 integrin, wherein the antibody comprises: HCDR1 of sequence GFTFSSSA (SEQ ID NO: 11), HCDR2 of sequence ISVGGST (SEQ ID NO: 27), and HCDR3 of sequence ARGGDYDAMDY (SEQ ID NO: 42); and LCDR1 of sequence QSISDY (SEQ ID NO: 56), LCDR2 of sequence YSS (SEQ ID NO: 67), and LCDR3 of sequence QNGHSFPFT (SEQ ID NO: 80).

26. An antibody or antigen-binding fragment that binds to α7β1 integrin, wherein the antibody comprises: HCDR1 of sequence GFTFSSSA (SEQ ID NO: 11), HCDR2 of sequence ISVGGST (SEQ ID NO: 27), and HCDR3 of sequence ARGGDYDPMDY (SEQ ID NO: 43); and LCDR1 with sequence QSISDY (SEQ ID NO: 56), LCDR2 with sequence YAS (SEQ ID NO: 66), and LCDR3 with sequence QNGHSFPFT (SEQ ID NO: 80).

27. An antibody or antigen-binding fragment that binds to α7β1 integrin, wherein the antibody comprises: HCDR1 of sequence GFTFSSDA (SEQ ID NO: 10), HCDR2 of sequence ISIGGST (SEQ ID NO: 28), and HCDR3 of sequence ARGGDYDAMDY (SEQ ID NO: 42); and LCDR1 with sequence QSISDL (SEQ ID NO: 55), LCDR2 with sequence YAS (SEQ ID NO: 66), and LCDR3 with sequence QNGHNFPFT (SEQ ID NO: 79).

28. An antibody or antigen-binding fragment that binds to α7β1 integrin, wherein the antibody comprises: HCDR1 of sequence GFTFSSSA (SEQ ID NO: 11), HCDR2 of sequence ISVGGSI (SEQ ID NO: 29), and HCDR3 of sequence ARGGDYDAMDY (SEQ ID NO: 42); and LCDR1 with sequence QSISDY (SEQ ID NO: 56), LCDR2 with sequence YAS (SEQ ID NO: 66), and LCDR3 with sequence QNGHSFPFT (SEQ ID NO: 80).

29. An antibody or antigen-binding fragment that binds to α7β1 integrin, wherein the antibody comprises: HCDR1 of sequence GFTFSSYS (SEQ ID NO: 3), HCDR2 of sequence ISTSSSYI (SEQ ID NO: 17), and HCDR3 of sequence ARRAWESDAFAI (SEQ ID NO: 33); and LCDR1 of sequence SLRSYY (SEQ ID NO: 47), LCDR2 of sequence GKN (SEQ ID NO: 59), and LCDR3 of sequence NSRDSSGNHVV (SEQ ID NO: 71); or HCDR1 of sequence GFTFSSYA (SEQ ID NO: 4), HCDR2 of sequence IHYSGGTT (SEQ ID NO: 19), and HCDR3 of sequence VKDGY (SEQ ID NO: 35); and LCDR1 of sequence QSLLDSDDGYTY (SEQ ID NO: 48), LCDR2 of sequence TLS (SEQ ID NO: 60), and LCDR3 of sequence MQRIEFPLT (SEQ ID NO: 72).

30. An antibody or antigen-binding fragment that binds to α7β1 integrin, wherein the antibody comprises: HCDR1 of sequence GFTFSNCA (SEQ ID NO: 12), HCDR2 of sequence ISIGGST (SEQ ID NO: 28), and HCDR3 of sequence ARGGDYDAMDY (SEQ ID NO: 42); and LCDR1 with sequence QSISDL (SEQ ID NO: 55), LCDR2 with sequence YAS (SEQ ID NO: 66), and LCDR3 with sequence QNGHSFPFT (SEQ ID NO: 80).

31. An antibody or antigen-binding fragment that binds to α7β1 integrin, wherein the antibody comprises: HCDR1 of sequence GFTFSSDA (SEQ ID NO: 10), HCDR2 of sequence ISIGGST (SEQ ID NO: 28), and HCDR3 of sequence TRGGDYDAMDY (SEQ ID NO: 44); and LCDR1 with sequence QSISDL (SEQ ID NO: 55), LCDR2 with sequence YAS (SEQ ID NO: 66), and LCDR3 with sequence QNGHNFPFT (SEQ ID NO: 79).

32. An antibody or antigen-binding fragment that binds to α7β1 integrin, wherein the antibody comprises: HCDR1 of sequence GFSLSTSDMG (SEQ ID NO: 13), HCDR2 of sequence IYWDDDK (SEQ ID NO: 30), and HCDR3 of sequence VRGTAVVAFYWYFDV (SEQ ID NO: 45); and LCDR1 with sequence QDINNY (SEQ ID NO: 57), LCDR2 with sequence RAN (SEQ ID NO: 68), and LCDR3 with sequence LHYDDFPLT (SEQ ID NO: 81).

33. An antibody or antigen-binding fragment that binds to α7β1 integrin, wherein the antibody comprises: HCDR1 of sequence GFSLSTSDLG (SEQ ID NO: 14), HCDR2 of sequence IYWDDDK (SEQ ID NO: 30), and HCDR3 of sequence VRGTAVVAFYWYFDV (SEQ ID NO: 45); and LCDR1 with sequence QDINNY (SEQ ID NO: 57), LCDR2 with sequence RAN (SEQ ID NO: 68), and LCDR3 with sequence LQYDDFPLT (SEQ ID NO: 82).

34. An antibody or antigen-binding fragment that binds to α7β1 integrin, wherein the antibody or antigen-binding fragment comprises: HCDR1 of sequence GYSFTRYW (SEQ ID NO: 101), HCDR2 of sequence IDPSDSET (SEQ ID NO: 102), and HCDR3 of sequence ARGGYFGREWYYDV (SEQ ID NO: 103); and LCDR1 of sequence QSLVHRNGNTY (SEQ ID NO: 105), LCDR2 of sequence EVS (SEQ ID NO: 106), and LCDR3 of sequence SQSTHVPWT (SEQ ID NO: 75).

35. An antibody or antigen-binding fragment that binds to α7β1 integrin, wherein the antibody or antigen-binding fragment comprises: HCDR1 of sequence GYSFTRYW (SEQ ID NO: 101), HCDR2 of sequence IDPSDSET (SEQ ID NO: 102), and HCDR3 of sequence ARGGYFGEEWYHDV (SEQ ID NO: 104); and LCDR1 of sequence QSLVHRNGNTY (SEQ ID NO: 105), LCDR2 of sequence EVS (SEQ ID NO: 106), and LCDR3 of sequence AQSTQLPYT (SEQ ID NO: 107).

36. An antibody or antigen-binding fragment that binds to α7β1 integrin, wherein the antibody comprises: HCDR1 of SEQ ID NO: 101, HCDR2 of SEQ ID NO: 102, HCDR3 of SEQ ID NO: 188, LCDR1 of SEQ ID NO: 105, LCDR2 of SEQ ID NO: 106, and LCDR3 of SEQ ID NO:

198.

37. An antibody or antigen-binding fragment that binds to α7β1 integrin, wherein the antibody comprises: HCDR1 of SEQ ID NO: 101, HCDR2 of SEQ ID NO: 102, HCDR3 of SEQ ID NO: 189, LCDR1 of SEQ ID NO: 105, LCDR2 of SEQ ID NO: 106, and LCDR3 of SEQ ID NO:

75.

38. An antibody or antigen-binding fragment that binds to α7β1 integrin, wherein the antibody comprises: HCDR1 of SEQ ID NO: 101, HCDR2 of SEQ ID NO: 102, HCDR3 of SEQ ID NO: 190, LCDR1 of SEQ ID NO: 105, LCDR2 of SEQ ID NO: 106, and LCDR3 of SEQ ID NO:

75.

39. An antibody or antigen-binding fragment that binds to α7β1 integrin, wherein the antibody comprises: HCDR1 of SEQ ID NO: 101, HCDR2 of SEQ ID NO: 102, HCDR3 of SEQ ID NO: 191, LCDR1 of SEQ ID NO: 105, LCDR2 of SEQ ID NO: 106, and LCDR3 of SEQ ID NO:

75.

40. An antibody or antigen-binding fragment that binds to α7β1 integrin, wherein the antibody comprises: HCDR1 of SEQ ID NO: 101, HCDR2 of SEQ ID NO: 102, HCDR3 of SEQ ID NO: 192, LCDR1 of SEQ ID NO: 105, LCDR2 of SEQ ID NO: 106, and LCDR3 of SEQ ID NO:

75.

41. An antibody or antigen-binding fragment that binds to α7β1 integrin, wherein the antibody comprises: HCDR1 of SEQ ID NO: 101, HCDR2 of SEQ ID NO: 102, HCDR3 of SEQ ID NO: 193, LCDR1 of SEQ ID NO: 105, LCDR2 of SEQ ID NO: 106, and LCDR3 of SEQ ID NO:

198.

42. An antibody or antigen-binding fragment that binds to α7β1 integrin, wherein the antibody comprises: HCDR1 of SEQ ID NO: 101, HCDR2 of SEQ ID NO: 102, HCDR3 of SEQ ID NO: 194, LCDR1 of SEQ ID NO: 105, LCDR2 of SEQ ID NO: 106, and LCDR3 of SEQ ID NO:

107.

43. An antibody or antigen-binding fragment that binds to α7β1 integrin, wherein the antibody comprises: HCDR1 of SEQ ID NO: 101, HCDR2 of SEQ ID NO: 102, HCDR3 of SEQ ID NO: 194, LCDR1 of SEQ ID NO: 105, LCDR2 of SEQ ID NO: 196, and LCDR3 of SEQ ID NO:

107.

44. An antibody or antigen-binding fragment that binds to α7β1 integrin, wherein the antibody comprises: HCDR1 of SEQ ID NO: 101, HCDR2 of SEQ ID NO: 102, HCDR3 of SEQ ID NO: 195, LCDR1 of SEQ ID NO: 105, LCDR2 of SEQ ID NO: 63, and LCDR3 of SEQ ID NO:

75.

45. An antibody or antigen-binding fragment that binds to α7β1 integrin, wherein the antibody comprises: HCDR1 of SEQ ID NO: 101, HCDR2 of SEQ ID NO: 102, HCDR3 of SEQ ID NO: 104, LCDR1 of SEQ ID NO: 105, LCDR2 of SEQ ID NO: 63, and LCDR3 of SEQ ID NO:

75.

46. ​​An antibody or antigen-binding fragment that binds to α7β1 integrin, wherein the antibody comprises: HCDR1 of SEQ ID NO: 101, HCDR2 of SEQ ID NO: 102, HCDR3 of SEQ ID NO: 104, LCDR1 of SEQ ID NO: 105, LCDR2 of SEQ ID NO: 197, and LCDR3 of SEQ ID NO:

75.

47. An antibody or antigen-binding fragment that binds to α7β1 integrin, wherein the antibody comprises: HCDR1 of SEQ ID NO: 101, HCDR2 of SEQ ID NO: 102, HCDR3 of SEQ ID NO: 190, LCDR1 of SEQ ID NO: 105, LCDR2 of SEQ ID NO: 106, and LCDR3 of SEQ ID NO:

198.

48. An antibody or antigen-binding fragment that binds to α7β1 integrin, wherein the antibody comprises: HCDR1 of SEQ ID NO: 101, HCDR2 of SEQ ID NO: 102, HCDR3 of SEQ ID NO: 189, LCDR1 of SEQ ID NO: 105, LCDR2 of SEQ ID NO: 197, and LCDR3 of SEQ ID NO:

107.

49. An antibody or antigen-binding fragment that binds to α7β1 integrin, wherein the antibody or antigen-binding fragment comprises: i) The variable heavy region containing the amino acid sequence of SEQ ID NO: 128 and the light chain variable region containing the amino acid sequence of SEQ ID NO: 129; ii) The variable heavy region comprising the amino acid sequence of SEQ ID NO: 130, and the light chain variable region comprising the amino acid sequence of SEQ ID NO: 131; iii) The variable heavy region containing the amino acid sequence of SEQ ID NO: 132, and the light chain variable region containing the amino acid sequence of SEQ ID NO: 133; iv) The variable heavy region containing the amino acid sequence of SEQ ID NO: 134, and the light chain variable region containing the amino acid sequence of SEQ ID NO: 135; v) A variable heavy region comprising the amino acid sequence of SEQ ID NO: 136, and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 137; vi) The variable heavy region comprising the amino acid sequence of SEQ ID NO: 138, and the light chain variable region comprising the amino acid sequence of SEQ ID NO: 139; or vii) The variable heavy region containing the amino acid sequence of SEQ ID NO: 140, and the light chain variable region containing the amino acid sequence of SEQ ID NO:

141.

50. An antibody or antigen-binding fragment that binds to α7β1 integrin, wherein the antibody or antigen-binding fragment comprises: The variable heavy region containing the amino acid sequence of SEQ ID NO: 130, and The light chain variable region containing the amino acid sequence of SEQ ID NO:

131.

51. An antibody or antigen-binding fragment that binds to α7β1 integrin, wherein the antibody or antigen-binding fragment comprises: i) a heavy chain containing the amino acid sequence of SEQ ID NO: 118, and a light chain containing the amino acid sequence of SEQ ID NO: 119; or ii) The heavy chain containing the amino acid sequence of SEQ ID NO: 120 and the light chain containing the amino acid sequence of SEQ ID NO:

121.

52. An antibody or antigen-binding fragment that binds to α7β1 integrin, wherein the antibody or antigen-binding fragment comprises: i) The variable heavy region containing the amino acid sequence of SEQ ID NO: 142 and the light chain variable region containing the amino acid sequence of SEQ ID NO: 143; ii) The variable heavy region containing the amino acid sequence of SEQ ID NO: 144, and the light chain variable region containing the amino acid sequence of SEQ ID NO: 145; iii) The variable heavy region containing the amino acid sequence of SEQ ID NO: 146, and the light chain variable region containing the amino acid sequence of SEQ ID NO: 147; iv) The variable heavy region comprising the amino acid sequence of SEQ ID NO: 148, and the light chain variable region comprising the amino acid sequence of SEQ ID NO: 149; v) A variable heavy region comprising the amino acid sequence of SEQ ID NO: 150, and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 151; vi) The variable heavy region containing the amino acid sequence of SEQ ID NO: 152 and the light chain variable region containing the amino acid sequence of SEQ ID NO: 153; vii) The variable heavy region containing the amino acid sequence of SEQ ID NO: 154, and the light chain variable region containing the amino acid sequence of SEQ ID NO: 155; viii) The variable heavy region containing the amino acid sequence of SEQ ID NO: 156, and the light chain variable region containing the amino acid sequence of SEQ ID NO: 157; ix) a variable heavy region comprising the amino acid sequence of SEQ ID NO: 158, and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 159; x) A variable heavy region containing the amino acid sequence of SEQ ID NO: 160, and a light chain variable region containing the amino acid sequence of SEQ ID NO: 161; xi) The variable heavy region containing the amino acid sequence of SEQ ID NO: 162, and the light chain variable region containing the amino acid sequence of SEQ ID NO: 163; xii) The variable heavy region comprising the amino acid sequence of SEQ ID NO: 164, and the light chain variable region comprising the amino acid sequence of SEQ ID NO: 165; xiii) The variable heavy region containing the amino acid sequence of SEQ ID NO: 166 and the light chain variable region containing the amino acid sequence of SEQ ID NO: 167; xiv) The variable heavy region comprising the amino acid sequence of SEQ ID NO: 170, and the light chain variable region comprising the amino acid sequence of SEQ ID NO: 171; or xv) a variable heavy region containing the amino acid sequence of SEQ ID NO: 172, and a light chain variable region containing the amino acid sequence of SEQ ID NO: 173; or xvi) contains a variable heavy region of the amino acid sequence of SEQ ID NO: 186 and a light chain variable region of the amino acid sequence of SEQ ID NO:

187.

53. An antibody or antigen-binding fragment that binds to α7β1 integrin, wherein the antibody or antigen-binding fragment comprises: The variable heavy region containing the amino acid sequence of SEQ ID NO: 142, and The light chain variable region containing the amino acid sequence of SEQ ID NO:

143.

54. An antibody or antigen-binding fragment that binds to α7β1 integrin, wherein the antibody or antigen-binding fragment comprises: i) The variable heavy region containing the amino acid sequence of SEQ ID NO: 108 and the light chain variable region containing the amino acid sequence of SEQ ID NO: 109; ii) The variable heavy region comprising the amino acid sequence of SEQ ID NO: 110, and the light chain variable region comprising the amino acid sequence of SEQ ID NO: 111; iii) The variable heavy region containing the amino acid sequence of SEQ ID NO: 199, and the light chain variable region containing the amino acid sequence of SEQ ID NO: 200; iv) The variable heavy region comprising the amino acid sequence of SEQ ID NO: 201, and the light chain variable region comprising the amino acid sequence of SEQ ID NO: 202; v) The variable heavy region containing the amino acid sequence of SEQ ID NO: 203 and the light chain variable region containing the amino acid sequence of SEQ ID NO: 204; vi) The variable heavy region containing the amino acid sequence of SEQ ID NO: 205, and the light chain variable region containing the amino acid sequence of SEQ ID NO: 206; vii) The variable heavy region containing the amino acid sequence of SEQ ID NO: 207 and the light chain variable region containing the amino acid sequence of SEQ ID NO: 208; viii) The variable heavy region comprising the amino acid sequence of SEQ ID NO: 209, and the light chain variable region comprising the amino acid sequence of SEQ ID NO: 210; ix) The variable heavy region comprising the amino acid sequence of SEQ ID NO: 211, and the light chain variable region comprising the amino acid sequence of SEQ ID NO: 212; x) The variable heavy region containing the amino acid sequence of SEQ ID NO: 213, and the light chain variable region containing the amino acid sequence of SEQ ID NO: 214; xi) The variable heavy region containing the amino acid sequence of SEQ ID NO: 215, and the light chain variable region containing the amino acid sequence of SEQ ID NO: 216; xii) The variable heavy region comprising the amino acid sequence of SEQ ID NO: 217, and the light chain variable region comprising the amino acid sequence of SEQ ID NO: 218; xiii) The variable heavy region containing the amino acid sequence of SEQ ID NO: 219 and the light chain variable region containing the amino acid sequence of SEQ ID NO: 220; xiv) The variable heavy region comprising the amino acid sequence of SEQ ID NO: 221, and the light chain variable region comprising the amino acid sequence of SEQ ID NO: 222; or xv) contains a variable heavy region of the amino acid sequence of SEQ ID NO: 223 and a light chain variable region of the amino acid sequence of SEQ ID NO:

224.

55. An antibody or antigen-binding fragment that binds to α7β1 integrin, wherein the antibody or antigen-binding fragment comprises: i) a heavy chain containing the amino acid sequence of SEQ ID NO: 112, and a light chain containing the amino acid sequence of SEQ ID NO: 113; ii) a heavy chain containing the amino acid sequence of SEQ ID NO: 114, and a light chain containing the amino acid sequence of SEQ ID NO: 113; iii) A heavy chain containing the amino acid sequence of SEQ ID NO: 115, and a light chain containing the amino acid sequence of SEQ ID NO: 116; or iv) The heavy chain containing the amino acid sequence of SEQ ID NO: 117, and the light chain containing the amino acid sequence of SEQ ID NO:

116.

56. The antibody or antigen-binding fragment according to any one of the preceding claims, wherein the antibody or antigen-binding fragment has an affinity (Kd) for α7β1 integrin or a fragment thereof between about 0.1 nM and 300 nM.

57. The antibody or antigen-binding fragment according to claim 56, wherein the α7β1 integrin or a fragment thereof is an α7β1 extracellular domain, a β1 extracellular domain, an α7 leg, a calf-1 domain, a calf-2 domain, or a calf-1 domain and a calf-2 domain.

58. The antibody or antigen-binding fragment according to claim 56, wherein the α7β1 integrin is human α7β1 integrin.

59. The antibody or antigen-binding fragment according to claim 58, wherein the antibody has an affinity of about 3 nM to 6 nM for the human α7β1 extracellular domain.

60. The antibody or antigen-binding fragment thereof according to any one of the preceding claims, wherein the antibody or antigen-binding fragment thereof activates α7β1 integrin with a maximum efficacy or Emax between about 100% and 300% compared to the 20TFT or TS2 / 16 antibody.

61. The antibody or antigen-binding fragment thereof according to any one of the preceding claims, wherein the antibody or antigen-binding fragment thereof has an EC50 value between 0.3 nM and 50 nM.

62. The antibody or antigen-binding fragment thereof according to any one of the preceding claims, wherein the antibody or antigen-binding fragment thereof specifically binds to α7β1 integrin and does not bind to α6β1 integrin or α3β1 integrin.

63. The antibody or antigen-binding fragment thereof according to any one of the preceding claims, wherein the antibody or antigen-binding fragment thereof is Fab, single-chain Fv (scFv), single-domain antibody (sdAb), VHH, variable heavy chain (VH), variable light chain (VL), Fab-like bispecific antibody (bsFab), single-domain antibody linked Fab (s-Fab), or a combination thereof.

64. The antibody or antigen-binding fragment thereof according to any one of the preceding claims, wherein the antibody or antigen-binding fragment thereof is a humanized antibody.

65. The antibody or antigen-binding fragment thereof according to any one of the preceding claims, wherein the antibody or antigen-binding fragment thereof is a human antibody.

66. The antibody or antigen-binding fragment thereof according to any one of the preceding claims, wherein the antibody or antigen-binding fragment thereof is a chimeric antibody.

67. The antibody or antigen-binding fragment thereof according to any one of the preceding claims, wherein the antibody or antigen-binding fragment thereof is IgG.

68. The antibody or antigen-binding fragment thereof according to claim 54, wherein the antibody or antigen-binding fragment thereof is derived from IgG1, IgG2, IgG3 or IgG4.

69. The antibody or antigen-binding fragment thereof according to any one of the preceding claims, wherein the antibody or antigen-binding fragment thereof contains an Fc region.

70. The antibody or antigen-binding fragment thereof according to claim 69, wherein the Fc region contains one or more mutations.

71. A method of treating a subject for a disease or disorder associated with a deficiency of α7β1 integrin, the method comprising administering to the subject an antibody or an antigen-binding fragment thereof according to any one of the preceding claims.

72. The method of claim 71, wherein the disease or disorder associated with α7β1 integrin deficiency is selected from a list including cardiomyopathy, congestive heart failure, and muscular dystrophy.

73. A method of treating a subject with muscular dystrophy, the method comprising administering to a subject in need an antibody or antigen-binding fragment according to any one of claims 1 to 70, wherein the administration results in improvement of one or more symptoms of the muscular dystrophy.

74. The method according to any one of claims 71 to 73, wherein the application is performed on muscle cells, wherein the muscle cells contain a mutation in the dystrophin gene.

75. The method of claim 74, wherein the muscle cells lack dystrophin or contain nonfunctional dystrophin.

76. The method according to any one of claims 73 to 75, wherein the muscular dystrophy is Duchenne muscular dystrophy, Beck muscular dystrophy, limb-girdle muscular dystrophy, Fukuyama type congenital muscular dystrophy (FCMD) or MDC1A type regional protein deficiency congenital muscular dystrophy.

77. The method of claim 76, wherein the muscular dystrophy is Duchenne muscular dystrophy.

78. The method of claim 76, wherein the muscular dystrophy is Becker muscular dystrophy.

79. The method according to any one of claims 73 to 78, wherein the administration reduces one or more serum biomarkers of myofibril damage.

80. The method of claim 79, wherein one or more biomarkers are creatine kinase, cytotoxic LDH, and / or IL-6.

81. The method according to any one of claims 73 to 80, wherein the application reduces muscle damage, inflammation, fibrosis, necrosis and / or atrophy.

82. The method according to any one of claims 73 to 81, wherein the application increases muscle cell adhesion.

83. A method for treating muscle atrophy in a subject, the method comprising administering to a subject in need an antibody or antigen-binding fragment according to any one of claims 1 to 70, wherein the administration results in an increase in α7 expression.

84. A method of treating muscle atrophy in a subject, the method comprising administering to a subject in need an antibody or antigen-binding fragment according to any one of claims 1 to 70, wherein the administration results in improvement of one or more symptoms of said muscle atrophy.

85. The method of claim 84, wherein, after administration of the antibody or its binding fragment, the subject has reduced muscle loss compared to a control.

86. The method of claim 84, wherein after administration of the antibody or its binding fragment, the subject has a muscle weight change of less than 20% compared to a control.

87. The method of claim 85 or 86, wherein the control is a baseline value prior to the administration of the antibody or its binding fragment.

88. The method according to claim 85 or 86, wherein the comparison is historical data.

89. The method of claim 85 or 86, wherein the control is a comparable subject to whom the antibody or its antigen-binding fragment has not been administered.

90. A pharmaceutical composition comprising an antibody or an antigen-binding fragment thereof according to any one of claims 1 to 70, and a pharmaceutically acceptable carrier.

91. The pharmaceutical composition according to claim 90, wherein the composition is for parenteral or oral administration.

92. The pharmaceutical composition of claim 90, wherein the composition is intended for administration via a route selected from intravenous, intradermal, transdermal, intraocular, intranasal, intramuscular, subcutaneous, and transmucosal routes.

93. A method for treating cardiomyopathy, congestive heart failure, or other myocardial disorders by administering an antibody or antigen-binding fragment thereof according to any one of claims 1 to 70 to a subject in need.

94. A method of treating muscular dystrophy in a subject, the method comprising administering a pharmaceutical composition to the subject in need, the pharmaceutical composition comprising: a) Antibody functional units for stabilizing the extended conformation of α7β1 integrin; and b) One or more physiologically acceptable carriers, excipients or diluents.

95. The antibody or antigen-binding fragment thereof according to any one of claims 1 to 70, wherein the antibody or the antigen-binding fragment binds to α7β1 integrin as measured by surface plasmon resonance (SPR) assay as described in Example 4.

96. A method of treating muscle atrophy in a subject, the method comprising administering a pharmaceutical composition to the subject in need, the pharmaceutical composition comprising: a) Antibody functional units for stabilizing the extended conformation of α7β1 integrin; and b) One or more physiologically acceptable carriers, excipients or diluents.

97. A method of treating muscle atrophy in a subject, the method comprising administering a pharmaceutical composition to the subject in need, the pharmaceutical composition comprising: a) Antibody functional units used to increase α7 expression; and b) One or more physiologically acceptable carriers, excipients or diluents.

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