Engineered CD200R antibodies and uses thereof

Abstract

In some aspects, provided herein are antibodies or antigen-binding fragments that bind to the glycoprotein receptor CD200R present on the surface of a cell. In some cases, the antibodies or antigen binding fragments provided herein agonize the CD200R signaling pathway that inhibits inflammatory and immune responses. In other aspects, provided herein are compositions, methods of use, methods of preparation, polynucleotides, vectors, host cells, and kits related to antibodies or antigen-binding fragments that bind to CD200R.

Description

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS

[0002] This application claims the benefit of U.S. Provisional Application No. 63 / 328,015 filed on April 6, 2022 and U.S. Provisional Application No. 63 / 348,532 filed on June 3, 2022 under 35 U.S.C. §119(e), which are hereby incorporated by reference in their entirety for all purposes.

[0003] Sequence Listing

[0004] This application contains a sequence listing, which is electronically submitted in .XML file format and is hereby incorporated by reference in its entirety. The .XML copy was created on March 31, 2023, is named 210196-209003_PCT.xml, and is 112,069 bytes in size. Summary of the invention

[0005] In some aspects, disclosed herein is an antibody or antigen-binding fragment thereof that specifically binds to CD200R, the antibody or antigen-binding fragment thereof comprising a heavy chain comprising at least one heavy chain complementarity determining region (CDR) as shown in any one of SEQ ID NO: 3, 4, 41, 5, 11, 12, 13, 19, 20, 21, 27, 28, 29, 35, 36, 37, 69, 70 or 91 having 0 to 3 amino acid modifications.

[0006] In some aspects, disclosed herein is an antibody or antigen-binding fragment thereof that specifically binds to CD200R, the antibody or antigen-binding fragment thereof comprising a heavy chain and a light chain, wherein the heavy chain comprises a heavy chain variable region comprising a heavy chain complementary determining region 1 (CDRH1), CDRH2 and CDRH3, and wherein CDRH1, CDRH2 and CDRH3 comprise: (a) the sequences shown in SEQ ID NOs: 3, 41 and 70, respectively, each having 0 to 3 amino acid modifications, such as 0, 1, 2 or 3 modifications; (b) the sequences shown in SEQ ID NOs: 3, 41 and 69, respectively, each having 0 to 3 amino acid modifications, such as 0, 1, 2 or 3 modifications; (c) the sequences shown in SEQ ID NOs: 3, 4 and 5, respectively, each having 0 to 3 amino acid modifications, such as 0, 1, 2 or 3 modifications; (d) the sequences shown in SEQ ID NOs: 3, 4 and 5, respectively, each having 0 to 3 amino acid modifications, such as 0, 1, 2 or 3 modifications; NO:3, 41 and 5, each having 0 to 3 amino acid modifications, such as 0, 1, 2 or 3 modifications; (e) the sequences shown in SEQ ID NO:11, 12 and 13, each having 0 to 3 amino acid modifications, such as 0, 1, 2 or 3 modifications; (f) the sequences shown in SEQ ID NO:19, 20 and 21, each having 0 to 3 amino acid modifications, such as 0, 1, 2 or 3 modifications; (g) the sequences shown in SEQ ID NO:27, 28 and 29, each having 0 to 3 amino acid modifications, such as 0, 1, 2 or 3 modifications; or (h) the sequences shown in SEQ ID NO:35, 36 and 37, each having 0 to 3 amino acid modifications, such as 0, 1, 2 or 3 modifications.

[0007] In some aspects, disclosed herein is an antibody or antigen-binding fragment thereof that specifically binds to CD200R, the antibody or antigen-binding fragment thereof comprising a light chain comprising at least one light chain complementary determining region (CDR) as shown in any one of SEQ ID NO: 6, 7, 8, 14, 15, 16, 22, 23, 24, 30, 31, 32, 38, 39, 40, 67, 68, or 87 to 91 having 0 to 3 amino acid modifications.

[0008] In some aspects, disclosed herein is an antibody or antigen-binding fragment thereof, comprising a heavy chain and a light chain, wherein the light chain comprises a light chain variable region comprising a light chain complementary determining region 1 (CDRL1), CDRL2 and CDRL3, and wherein CDRL1, CDRL2 and CDRL3 comprise: (a) the sequences shown in SEQ ID NOs: 6, 7 and 8, respectively, each having 0 to 3 amino acid modifications, such as 0, 1, 2 or 3 modifications; (b) the sequences shown in SEQ ID NOs: 14, 15 and 16, respectively, each having 0 to 3 amino acid modifications, such as 0, 1, 2 or 3 modifications; (c) the sequences shown in SEQ ID NOs: 22, 23 and 24, respectively, each having 0 to 3 amino acid modifications, such as 0, 1, 2 or 3 modifications; (d) the sequences shown in SEQ ID NOs: 30, 31 and 32, respectively, each having 0 to 3 amino acid modifications, such as 0, 1, 2 or 3 modifications; (e) the sequences shown in SEQ ID NOs: 31, 32 and 33, respectively, each having 0 to 3 amino acid modifications, such as 0, 1, 2 or 3 modifications; (f) the sequences shown in SEQ ID NOs: 6, 67 and 8, respectively, each having 0 to 3 amino acid modifications, such as 0, 1, 2 or 3 modifications; or (g) the sequences shown in SEQ ID NOs: 6, 68 and 8, respectively, each having 0 to 3 amino acid modifications, such as 0, 1, 2 or 3 modifications.

[0009] In some aspects, disclosed herein is an antibody or antigen-binding fragment thereof that specifically binds to CD200R, the antibody or antigen-binding fragment thereof comprising: (a) a heavy chain comprising at least one heavy chain CDR as shown in any one of SEQ ID NO: 3, 4, 41, 5, 69 or 70 with 0 to 3 amino acid modifications, and a light chain comprising at least one light chain CDR as shown in any one of SEQ ID NO: 6, 7 or 8 with 0 to 3 amino acid modifications; (b) a heavy chain comprising at least one heavy chain CDR as shown in any one of SEQ ID NO: 3, 4, 41, 5, 69 or 70 with 0 to 3 amino acid modifications, and a light chain comprising at least one light chain CDR as shown in any one of SEQ ID NO: 6, 67 or 8 with 0 to 3 amino acid modifications; (c) a heavy chain comprising at least one heavy chain CDR as shown in any one of SEQ ID NO: 3, 4, 41, 5, 69 or 70 with 0 to 3 amino acid modifications, and a light chain comprising at least one light chain CDR as shown in any one of SEQ ID NO: 6, 67 or 8 with 0 to 3 amino acid modifications. NO:6, 68 or 8; (d) comprising at least one heavy chain CDR as shown in any one of SEQ ID NO:3, 41 or 70 with 0 to 3 amino acid modifications, and comprising at least one light chain CDR as shown in any one of SEQ ID NO:6, 67 or 8 with 0 to 3 amino acid modifications; (e) comprising at least one heavy chain CDR as shown in any one of SEQ ID NO:3, 41 or 69 with 0 to 3 amino acid modifications, and comprising at least one light chain CDR as shown in any one of SEQ ID NO:6, 67 or 8 with 0 to 3 amino acid modifications; (f) comprising at least one heavy chain CDR as shown in any one of SEQ ID NO:11, 12 or 13 with 0 to 3 amino acid modifications, and comprising at least one light chain CDR as shown in any one of SEQ ID NO:11, 12 or 13 with 0 to 3 amino acid modifications NO: 14, 15 or 16 as shown in any one of the light chain CDR; (g) comprising at least one heavy chain CDR as shown in any one of SEQ ID NO: 19, 20 or 21 with 0 to 3 amino acid modifications, and comprising at least one light chain CDR as shown in any one of SEQ ID NO: 22, 23 or 24 with 0 to 3 amino acid modifications; (h) comprising at least one heavy chain CDR as shown in any one of SEQ ID NO: 27, 28 or 29 with 0 to 3 amino acid modifications, and comprising at least one light chain CDR as shown in any one of SEQ ID NO: 30, 31 or 32 with 0 to 3 amino acid modifications;or (i) a heavy chain comprising at least one heavy chain CDR as shown in any one of SEQ ID NOs: 35, 36 or 37 with 0 to 3 amino acid modifications, and a light chain comprising at least one light chain CDR as shown in any one of SEQ ID NOs: 38, 39 or 40 with 0 to 3 amino acid modifications. ;

[0010] In some aspects, disclosed herein is an antibody or antigen-binding fragment thereof, comprising a heavy chain and a light chain, wherein: (1) the heavy chain comprises a heavy chain variable region, the heavy chain variable region comprising a heavy chain complementary determining region 1 (CDRH1), CDRH2 and CDRH3, wherein CDRH1, CDRH2 and CDRH3 respectively comprise the sequences shown in SEQ ID NOs: 3, 41 and 70, each having 0 to 3 amino acid modifications, such as 0, 1, 2 or 3 modifications; and the light chain comprises a light chain variable region, the light chain variable region comprising a light chain complementary determining region 1 (CDRL1), CDRL2 and CDRL3, wherein CDRL1, CDRL2 and CDRL3 respectively comprise the sequences shown in SEQ ID NOs: 3, 41 and 70, each having 0 to 3 amino acid modifications, such as 0, 1, 2 or 3 modifications. NO:6, 67 and 8; (2) the heavy chain comprises a heavy chain variable region, the heavy chain variable region comprises a heavy chain complementary determining region 1 (CDRH1), CDRH2 and CDRH3, wherein CDRH1, CDRH2 and CDRH3 respectively comprise the sequences as shown in SEQ ID NO:3, 41 and 5, each having 0 to 3 amino acid modifications, such as 0, 1, 2 or 3 modifications; and the light chain comprises a light chain variable region, the light chain variable region comprises a light chain complementary determining region 1 (CDRL1), CDRL2 and CDRL3, wherein CDRL1, CDRL2 and CDRL3 respectively comprise the sequences as shown in SEQ ID NO:3, 41 and 5, each having 0 to 3 amino acid modifications, such as 0, 1, 2 or 3 modifications. NO:6, 67 and 8; (3) the heavy chain comprises a heavy chain variable region, the heavy chain variable region comprises a heavy chain complementary determining region 1 (CDRH1), CDRH2 and CDRH3, wherein CDRH1, CDRH2 and CDRH3 respectively comprise the sequences as shown in SEQ ID NO:3, 4 and 5, each having 0 to 3 amino acid modifications, such as 0, 1, 2 or 3 modifications; and the light chain comprises a light chain variable region, the light chain variable region comprises a light chain complementary determining region 1 (CDRL1), CDRL2 and CDRL3, wherein CDRL1, CDRL2 and CDRL3 respectively comprise the sequences as shown in SEQ ID NO:3, 4 and 5, each having 0 to 3 amino acid modifications, such as 0, 1, 2 or 3 modifications. NO:6, 7 and 8; (4) the heavy chain comprises a heavy chain variable region, the heavy chain variable region comprises heavy chain CDRH1, CDRH2 and CDRH3, and wherein CDRH1, CDRH2 and CDRH3 respectively comprise the sequences shown in SEQ ID NO:3, 41 and 5, each having 0 to 3 amino acid modifications, such as 0, 1, 2 or 3 modifications;and the light chain comprises a light chain variable region, the light chain variable region comprises CDRL1, CDRL2 and CDRL3, and wherein CDRL1, CDRL2 and CDRL3 respectively comprise the sequences shown in SEQ ID NOs: 6, 7 and 8, each having 0 to 3 amino acid modifications, such as 0, 1, 2 or 3 modifications; (5) the heavy chain comprises a heavy chain variable region, the heavy chain variable region comprises CDRH1, CDRH2 and CDRH3, and wherein CDRH1, CDRH2 and CDRH3 respectively comprise the sequences shown in SEQ ID NOs: 11, 12 and 13, each having 0 to 3 amino acid modifications, such as 0, 1, 2 or 3 modifications; and the light chain comprises a light chain variable region, the light chain variable region comprises CDRL1, CDRL2 and CDRL3, and wherein CDRL1, CDRL2 and CDRL3 respectively comprise the sequences shown in SEQ ID NOs: 11, 12 and 13, each having 0 to 3 amino acid modifications, such as 0, 1, 2 or 3 modifications. NO:14, 15 and 16; (6) the heavy chain comprises a heavy chain variable region, the heavy chain variable region comprises CDRH1, CDRH2 and CDRH3, and wherein CDRH1, CDRH2 and CDRH3 respectively comprise the sequences shown in SEQ ID NO:19, 20 and 21, each having 0 to 3 amino acid modifications, such as 0, 1, 2 or 3 modifications; and the light chain comprises a light chain variable region, the light chain variable region comprises CDRL1, CDRL2 and CDRL3, and wherein CDRL1, CDRL2 and CDRL3 respectively comprise the sequences shown in SEQ ID NO:22, 23 and 24, each having 0 to 3 amino acid modifications, such as 0, 1, 2 or 3 modifications; (7) the heavy chain comprises a heavy chain variable region, the heavy chain variable region comprises CDRH1, CDRH2 and CDRH3, and wherein CDRH1, CDRH2 and CDRH3 respectively comprise the sequences shown in SEQ ID NO:22, 23 and 24, each having 0 to 3 amino acid modifications, such as 0, 1, 2 or 3 modifications. The invention relates to a polypeptide comprising a light chain variable region comprising a light chain variable region comprising CDRL1, CDRL2 and CDRL3, wherein CDRL1, CDRL2 and CDRL3 respectively comprise the sequences shown in SEQ ID NOs: 30, 31 and 32, each of which has 0 to 3 amino acid modifications, such as 0, 1, 2 or 3 modifications; (8) the invention relates to a polypeptide comprising a light chain variable region comprising a light chain variable region comprising CDRH1, CDRH2 and CDRH3, wherein CDRH1, CDRH2 and CDRH3 respectively comprise the sequences shown in SEQ ID NOs: 35, 36 and 37, each of which has 0 to 3 amino acid modifications, such as 0, 1, 2 or 3 modifications;and the light chain comprises a light chain variable region, the light chain variable region comprises CDRL1, CDRL2 and CDRL3, wherein CDRL1, CDRL2 and CDRL3 respectively comprise the sequences shown in SEQ ID NOs: 38, 39 and 40, each having 0 to 3 amino acid modifications, such as 0, 1, 2 or 3 modifications; (9) the heavy chain comprises a heavy chain variable region, the heavy chain variable region comprises a heavy chain complementary determining region 1 (CDRH1), CDRH2 and CDRH3, wherein CDRH1, CDRH2 and CDRH3 respectively comprise the sequences shown in SEQ ID NOs: 3, 4 and 5, each having 0 to 3 amino acid modifications, such as 0, 1, 2 or 3 modifications; and the light chain comprises a light chain variable region, the light chain variable region comprises a light chain complementary determining region 1 (CDRL1), CDRL2 and CDRL3, wherein CDRL1, CDRL2 and CDRL3 respectively comprise the sequences shown in SEQ ID NOs: 3, 4 and 5, each having 0 to 3 amino acid modifications, such as 0, 1, 2 or 3 modifications. NO:6, 67 and 8; or (10) the heavy chain comprises a heavy chain variable region, the heavy chain variable region comprises a heavy chain complementary determining region 1 (CDRH1), CDRH2 and CDRH3, wherein CDRH1, CDRH2 and CDRH3 respectively comprise the sequences shown in SEQ ID NO:3, 4 and 5, each having 0 to 3 amino acid modifications, such as 0, 1, 2 or 3 modifications; and the light chain comprises a light chain variable region, the light chain variable region comprises a light chain complementary determining region 1 (CDRL1), CDRL2 and CDRL3, wherein CDRL1, CDRL2 and CDRL3 respectively comprise the sequences shown in SEQ ID NO:6, 68 and 8, each having 0 to 3 amino acid modifications, such as 0, 1, 2 or 3 modifications. ;

[0011] In some aspects, disclosed herein is an antibody or antigen-binding fragment thereof, comprising a heavy chain and a light chain, wherein: the heavy chain comprises a heavy chain variable region comprising a heavy chain complementary determining region 1 (CDRH1), CDRH2, and CDRH3, wherein CDRH1, CDRH2, and CDRH3 comprise a sequence as shown in SEQ ID NOs: 3, 41, and 69, respectively, each having 0 to 3 amino acid modifications, such as 0, 1, 2, or 3 modifications; and the light chain comprises a light chain variable region comprising a light chain complementary determining region 1 (CDRL1), CDRL2, and CDRL3, wherein CDRL1, CDRL2, and CDRL3 comprise a sequence as shown in SEQ ID NOs: 6, 90, and 8, respectively, each having 0 to 3 amino acid modifications, such as 0, 1, 2, or 3 modifications. In some embodiments, X at position 1 of SEQ ID NO: 69 is M. In some embodiments, X at position 1 of SEQ ID NO: 69 is G. In some embodiments, X at position 7 of SEQ ID NO:90 is D.

[0012] Disclosed herein is an antibody or antigen-binding fragment thereof, wherein the antibody or antigen-binding fragment thereof comprises a heavy chain variable region (HCVR) and a light chain variable region (LCVR), wherein: (a) the HCVR comprises a heavy chain complementary determining region 1 (CDRH1), CDRH2 and CDRH3, and wherein CDRH1, CDRH2 and CDRH3 comprise the sequences shown in SEQ ID NOs: 3, 41 and 70, respectively, each having 0 to 3 amino acid modifications, such as 0, 1, 2 or 3 modifications; and (b) the LCVR comprises a light chain complementary determining region 1 (CDRL1), CDRL2 and CDRL3, and wherein CDRL1, CDRL2 and CDRL3 comprise the sequences shown in SEQ ID NOs: 6, 67 and 8, respectively, each having 0 to 3 amino acid modifications, such as 0, 1, 2 or 3 modifications. In some embodiments, the HCVR comprises an amino acid sequence having at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence set forth in SEQ ID NO: 72, and the LCVR comprises an amino acid sequence having at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence set forth in SEQ ID NO: 65. In some embodiments, the HCVR comprises the amino acid sequence set forth in SEQ ID NO: 72, with 0 to 10 amino acid modifications, such as 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid modifications, and the LCVR comprises the amino acid sequence set forth in SEQ ID NO: 65, with 0 to 10 amino acid modifications, such as 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid modifications.

[0013] Disclosed herein is an antibody or antigen-binding fragment thereof, wherein the antibody or antigen-binding fragment thereof comprises a heavy chain variable region (HCVR) and a light chain variable region (LCVR), wherein: (a) the HCVR comprises a heavy chain complementary determining region 1 (CDRH1), CDRH2 and CDRH3, and wherein CDRH1, CDRH2 and CDRH3 comprise the sequences shown in SEQ ID NOs: 3, 41 and 5, respectively, each having 0 to 3 amino acid modifications, such as 0, 1, 2 or 3 modifications; and (b) the LCVR comprises a light chain complementary determining region 1 (CDRL1), CDRL2 and CDRL3, and wherein CDRL1, CDRL2 and CDRL3 comprise the sequences shown in SEQ ID NOs: 6, 67 and 8, respectively, each having 0 to 3 amino acid modifications, such as 0, 1, 2 or 3 modifications. In some embodiments, the HCVR comprises an amino acid sequence having at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence set forth in SEQ ID NO: 71, and the LCVR comprises an amino acid sequence having at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence set forth in SEQ ID NO: 65. In some embodiments, the HCVR comprises the amino acid sequence set forth in SEQ ID NO: 71, with 0 to 10 amino acid modifications, such as 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid modifications, and the LCVR comprises the amino acid sequence set forth in SEQ ID NO: 65, with 0 to 10 amino acid modifications, such as 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid modifications.

[0014] In some aspects, disclosed herein is an antibody or antigen-binding fragment thereof, comprising a heavy chain and a light chain, wherein: (a) the heavy chain comprises a heavy chain variable region comprising (i) a heavy chain complementary determining region 1 (CDRH1) comprising a sequence as set forth in SEQ ID NO: 92, (ii) a CDRH2 comprising a sequence as set forth in SEQ ID NO: 41, and (iii) a CDRH3 comprising a sequence as set forth in SEQ ID NO: 69; and (b) the light chain comprises a light chain variable region comprising (i) a light chain complementary determining region 1 (CDRL1) comprising a sequence as set forth in SEQ ID NO: 6, (ii) a CDRL2 comprising a sequence selected from the group consisting of SEQ ID NOs: 87 to 90, and (iii) a CDRL3 comprising a sequence as set forth in SEQ ID NO: 91. In some embodiments, X at position 1 of SEQ ID NO: 69 is M. In some embodiments, X at position 1 of SEQ ID NO: 69 is G. In some embodiments, X at position 8 of SEQ ID NO: 91 is W. In some embodiments, X at position 8 of SEQ ID NO:91 is F. In some embodiments, X at position 3 of SEQ ID NO:92 is W. In some embodiments, X at position 3 of SEQ ID NO:92 is F. In some embodiments, X at position 1 of SEQ ID NO:87, 88, or 89 is G. In some embodiments, X at position 1 of SEQ ID NO:87, 88, or 89 is L. In some embodiments, X at position 2 of SEQ ID NO:87 or 90 is A. In some embodiments, X at position 2 of SEQ ID NO:87 or 90 is G. In some embodiments, X at position 3 of SEQ ID NO:87 or 88 is S. In some embodiments, X at position 3 of SEQ ID NO:87 or 88 is V. In some embodiments, X at position 7 of SEQ ID NO:87, 88, 89, or 90 is D. In some embodiments, X at position 7 of SEQ ID NO:87, 88, 89, or 90 is S. In some embodiments, X at position 7 of SEQ ID NO:87, 88, 89 or 90 is T. In some embodiments, the HCVR comprises an amino acid sequence having at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence set forth in SEQ ID NO:72, and the LCVR comprises an amino acid sequence having at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence set forth in SEQ ID NO:65.In some embodiments, the HCVR comprises an amino acid sequence as set forth in SEQ ID NO:72, with 0 to 10 amino acid modifications, and the LCVR comprises an amino acid sequence as set forth in SEQ ID NO:65, with 0 to 10 amino acid modifications. In some embodiments, the HCVR comprises an amino acid sequence having at least 90%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to an amino acid sequence as set forth in SEQ ID NO:71, and the LCVR comprises an amino acid sequence having at least 90%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to an amino acid sequence as set forth in SEQ ID NO:65. In some embodiments, the HCVR comprises an amino acid sequence as set forth in SEQ ID NO:71, with 0 to 10 amino acid modifications, and the LCVR comprises an amino acid sequence as set forth in SEQ ID NO:65, with 0 to 10 amino acid modifications. In some embodiments, the HCVR comprises an amino acid sequence having at least 90%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to the amino acid sequence set forth in SEQ ID NO: 45, and the LCVR comprises an amino acid sequence having at least 90%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to the amino acid sequence set forth in SEQ ID NO: 65. In some embodiments, the HCVR comprises the amino acid sequence set forth in SEQ ID NO: 45, having 0 to 10 amino acid modifications, and the LCVR comprises the amino acid sequence set forth in SEQ ID NO: 65, having 0 to 10 amino acid modifications. In some embodiments, the HCVR comprises an amino acid sequence having at least 90%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to the amino acid sequence set forth in SEQ ID NO: 93, and the LCVR comprises an amino acid sequence having at least 90%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to the amino acid sequence set forth in SEQ ID NO: 94. In some embodiments, the HCVR comprises an amino acid sequence set forth in SEQ ID NO: 93, having 0 to 10 amino acid modifications, such as 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 modifications, and the LCVR comprises an amino acid sequence set forth in SEQ ID NO: 94, having 0 to 10 amino acid modifications, such as 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 modifications. In some embodiments, X at position 1 of SEQ ID NO:93 is D. In some embodiments, X at position 1 of SEQ ID NO:93 is E.In some embodiments, X at position 33 of SEQ ID NO:93 is W. In some embodiments, X at position 33 of SEQ ID NO:93 is F. In some embodiments, X at position 99 of SEQ ID NO:93 is M. In some embodiments, X at position 99 of SEQ ID NO:93 is G. In some embodiments, X at position 50 of SEQ ID NO:94 is G. In some embodiments, X at position 50 of SEQ ID NO:94 is L. In some embodiments, X at position 51 of SEQ ID NO:94 is A. In some embodiments, X at position 51 of SEQ ID NO:94 is G. In some embodiments, X at position 52 of SEQ ID NO:94 is S. In some embodiments, X at position 52 of SEQ ID NO:94 is V. In some embodiments, X at position 56 of SEQ ID NO:94 is D. In some embodiments, X at position 56 of SEQ ID NO:94 is S. In some embodiments, X at position 56 of SEQ ID NO:94 is T. In some embodiments, X at position 96 of SEQ ID NO:94 is W. In some embodiments, X at position 96 of SEQ ID NO:94 is F. In some embodiments, the LCVR is linked to a light chain constant region comprising an amino acid sequence having at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence shown in SEQ ID NO:62. In some embodiments, the light chain variable region is linked to a light chain constant region comprising an amino acid sequence as shown in SEQ ID NO:62 with 0 to 10 amino acid modifications. In some embodiments, the light chain variable region is linked to a light chain constant region comprising an amino acid sequence having at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence shown in SEQ ID NO:64. In some embodiments, the light chain variable region is linked to a light chain constant region comprising an amino acid sequence as shown in SEQ ID NO: 64 with 0 to 10 amino acid modifications. In some embodiments, the HCVR is linked to a heavy chain constant region comprising an amino acid sequence having at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence as shown in SEQ ID NO: 61. In some embodiments, the HCVR is linked to a heavy chain constant region comprising an amino acid sequence as shown in SEQ ID NO: 61 with 0 to 10 amino acid modifications.In some embodiments, the HCVR is linked to a heavy chain constant region comprising an amino acid sequence having at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence as shown in SEQ ID NO: 63. In some embodiments, the HCVR is linked to a heavy chain constant region comprising an amino acid sequence as shown in SEQ ID NO: 63 with 0 to 10 amino acid modifications. In some embodiments, the HCVR is linked to a heavy chain constant region comprising an amino acid sequence having at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence as shown in SEQ ID NO: 75. In some embodiments, the HCVR is linked to a heavy chain constant region comprising an amino acid sequence as shown in SEQ ID NO: 75 with 0 to 10 amino acid modifications. In some embodiments, the HCVR is linked to a heavy chain constant region comprising an amino acid sequence having at least 90%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to the amino acid sequence as set forth in SEQ ID NO: 76. In some embodiments, the HCVR is linked to a heavy chain constant region comprising the amino acid sequence as set forth in SEQ ID NO: 76 with 0 to 10 amino acid modifications. In some embodiments, the HCVR is linked to a heavy chain constant region, wherein the heavy chain constant region comprises an Fc region comprising one or more of the following amino acids: alanine (A) at position 234, alanine (A) at position 235, aspartic acid (D) at position 236, aspartic acid (D) at position 237, aspartic acid (D) at position 238, alanine (A) at position 265, glutamic acid (E) at position 267, glycine (G) at position 271, arginine (R) at position 330, alanine (A) at position 332, or alanine (A) at position 297 (numbering according to the EU index). In some embodiments, the Fc region comprises aspartic acid (D) at position 238 (EU index). In some embodiments, the HCVR is linked to a heavy chain constant region comprising an amino acid sequence having at least 90%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to the amino acid sequence shown in SEQ ID NO: 77. In some embodiments, the HCVR is linked to a heavy chain constant region comprising an amino acid sequence as set forth in SEQ ID NO: 77 with 0 to 10 amino acid modifications. In some embodiments, X at position 121 of SEQ ID NO: 77 is D. In some embodiments, X at position 121 of SEQ ID NO: 77 is P. In some embodiments, X at position 329 of SEQ ID NO: 77 is G.In some embodiments, X at position 329 of SEQ ID NO:77 is absent. In some embodiments, X at position 330 of SEQ ID NO:77 is K. In some embodiments, X at position 330 of SEQ ID NO:77 is absent. In some embodiments, the HCVR is linked to a heavy chain constant region comprising an amino acid sequence having at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity with the amino acid sequence as shown in SEQ ID NO:78. In some embodiments, the HCVR is linked to a heavy chain constant region comprising an amino acid sequence as shown in SEQ ID NO:78 with 0 to 10 amino acid modifications. In some embodiments, X at position 108 of SEQ ID NO:78 is S. In some embodiments, X at position 108 of SEQ ID NO:78 is P. In some embodiments, X at position 326 of SEQ ID NO:78 is G. In some embodiments, X at position 326 of SEQ ID NO:78 is absent. In some embodiments, X at position 327 of SEQ ID NO: 78 is K. In some embodiments, X at position 327 of SEQ ID NO: 78 is absent.

[0015] In some aspects, disclosed herein is an antibody or antigen-binding fragment thereof, comprising a heavy chain and a light chain, wherein: the heavy chain comprises a heavy chain variable region comprising a heavy chain complementary determining region 1 (CDRH1), CDRH2 and CDRH3, wherein CDRH1, CDRH2 and CDRH3 comprise the sequences shown in SEQ ID NOs: 3, 41 and 69, respectively, each having 0 to 3 amino acid modifications; and the light chain comprises a light chain variable region comprising a light chain complementary determining region 1 (CDRL1), CDRL2 and CDRL3, wherein CDRL1, CDRL2 and CDRL3 comprise the sequences shown in SEQ ID NOs: 6, 90 and 8, respectively, each having 0 to 3 amino acid modifications. In some embodiments, X at position 1 of SEQ ID NO: 69 is M. In some embodiments, X at position 1 of SEQ ID NO: 69 is G. In some embodiments, X at position 7 of SEQ ID NO: 90 is D. In some embodiments, X at position 7 of SEQ ID NO: 90 is S. In some embodiments, X at position 7 of SEQ ID NO:90 is T. In some embodiments, the HCVR comprises an amino acid sequence having at least 90%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to the amino acid sequence set forth in SEQ ID NO:72, and the LCVR comprises an amino acid sequence having at least 90%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to the amino acid sequence set forth in SEQ ID NO:65. In some embodiments, the HCVR comprises the amino acid sequence set forth in SEQ ID NO:72, with 0 to 10 amino acid modifications, and the LCVR comprises the amino acid sequence set forth in SEQ ID NO:65, with 0 to 10 amino acid modifications. In some embodiments, the HCVR comprises an amino acid sequence having at least 90%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to the amino acid sequence set forth in SEQ ID NO: 71, and the LCVR comprises an amino acid sequence having at least 90%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to the amino acid sequence set forth in SEQ ID NO: 65. In some embodiments, the HCVR comprises the amino acid sequence set forth in SEQ ID NO: 71, having 0 to 10 amino acid modifications, and the LCVR comprises the amino acid sequence set forth in SEQ ID NO: 65, having 0 to 10 amino acid modifications.In some embodiments, the HCVR comprises an amino acid sequence having at least 90%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to the amino acid sequence set forth in SEQ ID NO: 45, and the LCVR comprises an amino acid sequence having at least 90%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to the amino acid sequence set forth in SEQ ID NO: 65. In some embodiments, the HCVR comprises the amino acid sequence set forth in SEQ ID NO: 45, having 0 to 10 amino acid modifications, and the LCVR comprises the amino acid sequence set forth in SEQ ID NO: 65, having 0 to 10 amino acid modifications. In some embodiments, the HCVR comprises an amino acid sequence having at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence set forth in SEQ ID NO: 93, and the LCVR comprises an amino acid sequence having at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence set forth in SEQ ID NO: 94. In some embodiments, the HCVR comprises an amino acid sequence set forth in SEQ ID NO: 93, having 0 to 10 amino acid modifications, such as 0, 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 modifications, and the LCVR comprises an amino acid sequence set forth in SEQ ID NO: 94, having 0 to 10 amino acid modifications, such as 0, 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 modifications. In some embodiments, X at position 1 of SEQ ID NO:93 is D. In some embodiments, X at position 1 of SEQ ID NO:93 is E. In some embodiments, X at position 33 of SEQ ID NO:93 is W. In some embodiments, X at position 33 of SEQ ID NO:93 is F. In some embodiments, X at position 99 of SEQ ID NO:93 is M. In some embodiments, X at position 99 of SEQ ID NO:93 is G. In some embodiments, X at position 50 of SEQ ID NO:94 is G. In some embodiments, X at position 50 of SEQ ID NO:94 is L. In some embodiments, X at position 51 of SEQ ID NO:94 is A. In some embodiments, X at position 51 of SEQ ID NO:94 is G. In some embodiments, X at position 52 of SEQ ID NO:94 is S. In some embodiments, X at position 52 of SEQ ID NO:94 is V. In some embodiments, X at position 56 of SEQ ID NO:94 is D.In some embodiments, X at position 56 of SEQ ID NO:94 is S. In some embodiments, X at position 56 of SEQ ID NO:94 is T. In some embodiments, X at position 96 of SEQ ID NO:94 is W. In some embodiments, X at position 96 of SEQ ID NO:94 is F. In some embodiments, the LCVR is linked to a light chain constant region comprising an amino acid sequence having at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence shown in SEQ ID NO:62. In some embodiments, the light chain variable region is linked to a light chain constant region comprising an amino acid sequence shown in SEQ ID NO:62 with 0 to 10 amino acid modifications. In some embodiments, the light chain variable region is linked to a light chain constant region, which comprises an amino acid sequence having at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity with the amino acid sequence as shown in SEQ ID NO: 64. In some embodiments, the light chain variable region is linked to a light chain constant region, which comprises an amino acid sequence as shown in SEQ ID NO: 64 with 0 to 10 amino acid modifications. In some embodiments, the HCVR is linked to a heavy chain constant region, which comprises an amino acid sequence having at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity with the amino acid sequence as shown in SEQ ID NO: 61. In some embodiments, the HCVR is linked to a heavy chain constant region, which comprises an amino acid sequence as shown in SEQ ID NO: 61 with 0 to 10 amino acid modifications. In some embodiments, the HCVR is linked to a heavy chain constant region comprising an amino acid sequence having at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence as shown in SEQ ID NO: 63. In some embodiments, the HCVR is linked to a heavy chain constant region comprising an amino acid sequence as shown in SEQ ID NO: 63 with 0 to 10 amino acid modifications. In some embodiments, the HCVR is linked to a heavy chain constant region comprising an amino acid sequence having at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence as shown in SEQ ID NO: 75. In some embodiments, the HCVR is linked to a heavy chain constant region comprising an amino acid sequence as shown in SEQ ID NO: 75 with 0 to 10 amino acid modifications.In some embodiments, the HCVR is linked to a heavy chain constant region comprising an amino acid sequence having at least 90%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to the amino acid sequence as set forth in SEQ ID NO: 76. In some embodiments, the HCVR is linked to a heavy chain constant region comprising the amino acid sequence as set forth in SEQ ID NO: 76 with 0 to 10 amino acid modifications. In some embodiments, the HCVR is linked to a heavy chain constant region, wherein the heavy chain constant region comprises an Fc region comprising one or more of the following amino acids: alanine (A) at position 234, alanine (A) at position 235, aspartic acid (D) at position 236, aspartic acid (D) at position 237, aspartic acid (D) at position 238, alanine (A) at position 265, glutamic acid (E) at position 267, glycine (G) at position 271, arginine (R) at position 330, alanine (A) at position 332, or alanine (A) at position 297 (numbering according to the EU index). In some embodiments, the Fc region comprises aspartic acid (D) at position 238 (EU index). In some embodiments, the HCVR is linked to a heavy chain constant region comprising an amino acid sequence having at least 90%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to the amino acid sequence shown in SEQ ID NO: 77. In some embodiments, the HCVR is linked to a heavy chain constant region comprising an amino acid sequence as set forth in SEQ ID NO: 77 having 0 to 10 amino acid modifications. In some embodiments, X at position 121 of SEQ ID NO: 77 is D. In some embodiments, X at position 121 of SEQ ID NO: 77 is P. In some embodiments, X at position 329 of SEQ ID NO: 77 is G. In some embodiments, X at position 329 of SEQ ID NO: 77 is absent. In some embodiments, X at position 330 of SEQ ID NO: 77 is K. In some embodiments, X at position 330 of SEQ ID NO: 77 is absent. In some embodiments, the HCVR is linked to a heavy chain constant region comprising an amino acid sequence having at least 90%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to an amino acid sequence as set forth in SEQ ID NO: 78. In some embodiments, the HCVR is linked to a heavy chain constant region comprising an amino acid sequence as set forth in SEQ ID NO: 78 with 0 to 10 amino acid modifications. In some embodiments, X at position 108 of SEQ ID NO: 78 is S.In some embodiments, X at position 108 of SEQ ID NO:78 is P. In some embodiments, X at position 326 of SEQ ID NO:78 is G. In some embodiments, X at position 326 of SEQ ID NO:78 is absent. In some embodiments, X at position 327 of SEQ ID NO:78 is K. In some embodiments, X at position 327 of SEQ ID NO:78 is absent.

[0016] In some cases, the antibody or antigen-binding fragment thereof comprises a heavy chain variable region comprising an amino acid sequence having at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence shown in SEQ ID NO:1, 9, 17, 25, 33, 42, 43, 44, 45, 46, 47, 71, 72 or 93.

[0017] In some cases, the antibody or antigen-binding fragment thereof comprises a heavy chain variable region comprising the amino acid sequence shown in SEQ ID NO: 1, 9, 17, 25, 33, 42, 43, 44, 45, 46, 47, 71, 72 or 93 having 0 to 3 amino acid modifications.

[0018] In some cases, the antibody or antigen-binding fragment thereof comprises a light chain variable region comprising an amino acid sequence having at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence shown in SEQ ID NO:2, 10, 18, 26, 34, 48, 49, 50, 51, 52, 65, 66 or 94.

[0019] In some cases, the antibody or antigen-binding fragment thereof comprises a light chain variable region comprising the amino acid sequence shown in SEQ ID NO: 2, 10, 18, 26, 34, 48, 49, 50, 51, 52, 65, 66 or 94 having 0 to 3 amino acid modifications.

[0020] In some cases, the antibody or antigen-binding fragment thereof comprises a heavy chain variable region and a light chain variable region, wherein: (a) the heavy chain variable region comprises an amino acid sequence that has at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence as shown in SEQ ID NO:72, and the light chain variable region comprises an amino acid sequence that has at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence as shown in SEQ ID NO:65; (b) the heavy chain variable region comprises an amino acid sequence that has at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence as shown in SEQ ID NO:71, and the light chain variable region comprises an amino acid sequence that has at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence as shown in SEQ ID NO: NO:65 has at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity; (c) the heavy chain variable region comprises an amino acid sequence that has at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence as shown in SEQ ID NO:1, and the light chain variable region comprises an amino acid sequence that has at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence as shown in SEQ ID NO:2; (d) the heavy chain variable region comprises an amino acid sequence that has at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence as shown in SEQ ID NO:9, and the light chain variable region comprises an amino acid sequence that has at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence as shown in SEQ ID NO:1 NO:10; (e) the heavy chain variable region comprises an amino acid sequence that has at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence as shown in SEQ ID NO:17, and the light chain variable region comprises an amino acid sequence that has at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence as shown in SEQ ID NO:18; (f) the heavy chain variable region comprises an amino acid sequence that has at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence as shown in SEQ ID NO:25, and the light chain variable region comprises an amino acid sequence that has at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence as shown in SEQ ID NO:26. An amino acid sequence having at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity with the amino acid sequence set forth in NO:26;(g) the heavy chain variable region comprises an amino acid sequence that has at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence as shown in SEQ ID NO:33, and the light chain variable region comprises an amino acid sequence that has at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence as shown in SEQ ID NO:34; (h) the heavy chain variable region comprises an amino acid sequence that has at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence as shown in SEQ ID NO:1, 42, 43, 44, 45, 46, 47, 71, 72 or 93, and the light chain variable region comprises an amino acid sequence that has at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence as shown in SEQ ID NO: NO:2, 48, 49, 50, 51, 52, 65, 66 or 94 has at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence shown in SEQ ID NO:2, 48, 49, 50, 51, 52, 65, 66 or 94; or (i) the heavy chain variable region comprises an amino acid sequence having at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence shown in SEQ ID NO:42, 43, 44, 45, 46, 47, 71, 72 or 93, and the light chain variable region comprises an amino acid sequence having at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence shown in SEQ ID NO:48, 49, 50, 51, 52, 65, 66 or 94.;

[0021] In some cases, the antibody or antigen-binding fragment thereof comprises a heavy chain variable region and a light chain variable region, wherein: (a) the heavy chain variable region comprises the amino acid sequence as shown in SEQ ID NO:72, having 0 to 10 amino acid modifications, such as 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid modifications, and the light chain variable region comprises the amino acid sequence as shown in SEQ ID NO:65, having 0 to 10 amino acid modifications, such as 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid modifications; (b) the heavy chain variable region comprises the amino acid sequence as shown in SEQ ID NO:71, having 0 to 10 amino acid modifications, such as 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid modifications, and the light chain variable region comprises the amino acid sequence as shown in SEQ ID NO:65, having 0 to 10 amino acid modifications, such as 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid modifications; NO:65, having 0 to 10 amino acid modifications, such as 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid modifications; (c) the heavy chain variable region comprises the amino acid sequence as shown in SEQ ID NO:1, having 0 to 10 amino acid modifications, such as 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid modifications, and the light chain variable region comprises the amino acid sequence as shown in SEQ ID NO:2, having 0 to 10 amino acid modifications, such as 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid modifications; (d) the heavy chain variable region comprises the amino acid sequence as shown in SEQ ID NO:9, having 0 to 10 amino acid modifications, such as 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid modifications, and the light chain variable region comprises the amino acid sequence as shown in SEQ ID NO: NO:10, having 0 to 10 amino acid modifications, such as 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid modifications; (e) the heavy chain variable region comprises the amino acid sequence as shown in SEQ ID NO:17, having 0 to 10 amino acid modifications, such as 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid modifications, and the light chain variable region comprises the amino acid sequence as shown in SEQ ID NO:18, having 0 to 10 amino acid modifications, such as 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid modifications;(f) the heavy chain variable region comprises the amino acid sequence as shown in SEQ ID NO: 25, having 0 to 10 amino acid modifications, such as 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid modifications, and the light chain variable region comprises the amino acid sequence as shown in SEQ ID NO: 26, having 0 to 10 amino acid modifications, such as 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid modifications; (g) the heavy chain variable region comprises the amino acid sequence as shown in SEQ ID NO: 33, having 0 to 10 amino acid modifications, such as 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid modifications, and the light chain variable region comprises the amino acid sequence as shown in SEQ ID NO: NO:34, having 0 to 10 amino acid modifications, such as 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid modifications; (h) the heavy chain variable region comprises the amino acid sequence as shown in any one of SEQ ID NO:1, 42, 43, 44, 45, 46, 47, 71, 72 or 93, having 0 to 10 amino acid modifications, such as 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid modifications, and the light chain variable region comprises the amino acid sequence as shown in SEQ ID NO:2, 48, 49, 50, 51, 52, 65, 66 or 94, having 0 to 10 amino acid modifications, such as 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid modifications; or (i) the heavy chain variable region comprises the amino acid sequence as shown in SEQ ID NO: NO:42, 43, 44, 45, 46, 47, 71, 72 or 93, with 0 to 10 amino acid modifications, such as 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid modifications, and the light chain variable region comprises an amino acid sequence as shown in SEQ ID NO:48, 49, 50, 51, 52, 65, 66 or 94, with 0 to 10 amino acid modifications, such as 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid modifications.;

[0022] In some aspects, disclosed herein is an antibody or antigen-binding fragment thereof that specifically binds to CD200R, wherein the antibody or antigen-binding fragment thereof comprises a heavy chain comprising a heavy chain variable region, and wherein the heavy chain variable region comprises an amino acid sequence having at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence shown in SEQ ID NO: 1, 9, 17, 25, 33, 42, 43, 44, 45, 46, 47, 71, 72 or 93.

[0023] In some aspects, disclosed herein is an antibody or antigen-binding fragment thereof that specifically binds to CD200R, wherein the antibody or antigen-binding fragment thereof comprises a heavy chain variable region, and wherein the heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO: 1, 9, 17, 25, 33, 42, 43, 44, 45, 46, 47, 71, 72 or 93, having 0 to 10 amino acid modifications, such as 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid modifications.

[0024] In some aspects, disclosed herein is an antibody or antigen-binding fragment thereof that specifically binds to CD200R, wherein the antibody or antigen-binding fragment thereof comprises a light chain comprising a light chain variable region, and wherein the light chain variable region comprises an amino acid sequence having at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence shown in SEQ ID NO: 2, 10, 18, 26, 34, 48, 49, 50, 51, 52, 65, 66 or 94.

[0025] In some aspects, disclosed herein is an antibody or antigen-binding fragment thereof that specifically binds to CD200R, wherein the antibody or antigen-binding fragment thereof comprises a light chain comprising a light chain variable region, and wherein the light chain variable region comprises the amino acid sequence shown in SEQ ID NO: 2, 10, 18, 26, 34, 48, 49, 50, 51, 52, 65, 66 or 94, having 0 to 10 amino acid modifications, such as 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid modifications.

[0026] In some cases, disclosed herein is an antibody or antigen-binding fragment thereof that specifically binds to CD200R, the antibody or antigen-binding fragment thereof comprising a heavy chain and a light chain, wherein the heavy chain comprises a heavy chain variable region, and the light chain comprises a light chain variable region, wherein: (a) the heavy chain variable region comprises an amino acid sequence that has at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence as shown in SEQ ID NO:72, and the light chain variable region comprises an amino acid sequence that has at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence as shown in SEQ ID NO:65; (b) the heavy chain variable region comprises an amino acid sequence that has at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence as shown in SEQ ID NO:71, and the light chain variable region comprises an amino acid sequence that has at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence as shown in SEQ ID NO: NO:65 has at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity; (c) the heavy chain variable region comprises an amino acid sequence that has at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence as shown in SEQ ID NO:1, and the light chain variable region comprises an amino acid sequence that has at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence as shown in SEQ ID NO:2; (d) the heavy chain variable region comprises an amino acid sequence that has at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence as shown in SEQ ID NO:9, and the light chain variable region comprises an amino acid sequence that has at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence as shown in SEQ ID NO:1 NO:10; (e) the heavy chain variable region comprises an amino acid sequence that has at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence as shown in SEQ ID NO:17, and the light chain variable region comprises an amino acid sequence that has at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence as shown in SEQ ID NO:18; (f) the heavy chain variable region comprises an amino acid sequence that has at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence as shown in SEQ ID NO:25, and the light chain variable region comprises an amino acid sequence that has at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence as shown in SEQ ID NO:26. An amino acid sequence having at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity with the amino acid sequence set forth in NO:26;(g) the heavy chain variable region comprises an amino acid sequence that has at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence as shown in SEQ ID NO:33, and the light chain variable region comprises an amino acid sequence that has at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence as shown in SEQ ID NO:34; (h) the heavy chain variable region comprises an amino acid sequence that has at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence as shown in SEQ ID NO:1, 42, 43, 44, 45, 46, 47, 71, 72 or 93, and the light chain variable region comprises an amino acid sequence that has at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence as shown in SEQ ID NO: NO:2, 48, 49, 50, 51, 52, 65, 66 or 94 has at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence shown in SEQ ID NO:2, 48, 49, 50, 51, 52, 65, 66 or 94; or (i) the heavy chain variable region comprises an amino acid sequence having at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence shown in SEQ ID NO:42, 43, 44, 45, 46, 47, 71, 72 or 93, and the light chain variable region comprises an amino acid sequence having at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence shown in SEQ ID NO:48, 49, 50, 51, 52, 65, 66 or 94.;

[0027] In some aspects, disclosed herein is an antibody or antigen-binding fragment thereof that specifically binds to CD200R, the antibody or antigen-binding fragment thereof comprising a heavy chain and a light chain, wherein the heavy chain comprises a heavy chain variable region and the light chain comprises a light chain variable region, wherein: (a) the heavy chain variable region comprises the amino acid sequence as shown in SEQ ID NO: 72, having 0 to 10 amino acid modifications, such as 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid modifications, and the light chain variable region comprises the amino acid sequence as shown in SEQ ID NO: 65, having 0 to 10 amino acid modifications, such as 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid modifications; (b) the heavy chain variable region comprises the amino acid sequence as shown in SEQ ID NO: NO:71, having 0 to 10 amino acid modifications, such as 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid modifications, and the light chain variable region comprises the amino acid sequence as shown in SEQ ID NO:65, having 0 to 10 amino acid modifications, such as 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid modifications; (c) the heavy chain variable region comprises the amino acid sequence as shown in SEQ ID NO:1, having 0 to 10 amino acid modifications, such as 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid modifications, and the light chain variable region comprises the amino acid sequence as shown in SEQ ID NO:2, having 0 to 10 amino acid modifications, such as 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid modifications; (d) the heavy chain variable region comprises the amino acid sequence as shown in SEQ ID NO: NO:9, having 0 to 10 amino acid modifications, such as 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid modifications, and the light chain variable region comprises the amino acid sequence as shown in SEQ ID NO:10, having 0 to 10 amino acid modifications, such as 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid modifications; (e) the heavy chain variable region comprises the amino acid sequence as shown in SEQ ID NO:17, having 0 to 10 amino acid modifications, such as 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid modifications, and the light chain variable region comprises the amino acid sequence as shown in SEQ ID NO:18, having 0 to 10 amino acid modifications, such as 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid modifications;(f) the heavy chain variable region comprises the amino acid sequence as shown in SEQ ID NO: 25, having 0 to 10 amino acid modifications, such as 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid modifications, and the light chain variable region comprises the amino acid sequence as shown in SEQ ID NO: 26, having 0 to 10 amino acid modifications, such as 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid modifications; (g) the heavy chain variable region comprises the amino acid sequence as shown in SEQ ID NO: 33, having 0 to 10 amino acid modifications, such as 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid modifications, and the light chain variable region comprises the amino acid sequence as shown in SEQ ID NO: NO:34, having 0 to 10 amino acid modifications, such as 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid modifications; (h) the heavy chain variable region comprises the amino acid sequence as shown in any one of SEQ ID NO:1, 42, 43, 44, 45, 46, 47, 71, 72 or 93, having 0 to 10 amino acid modifications, such as 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid modifications, and the light chain variable region comprises the amino acid sequence as shown in SEQ ID NO:2, 48, 49, 50, 51, 52, 65, 66 or 94, having 0 to 10 amino acid modifications, such as 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid modifications; or (i) the heavy chain variable region comprises the amino acid sequence as shown in SEQ ID NO: NO:42, 43, 44, 45, 46, 47, 71, 72 or 93, with 0 to 10 amino acid modifications, such as 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid modifications, and the light chain variable region comprises an amino acid sequence as shown in SEQ ID NO:48, 49, 50, 51, 52, 65, 66 or 94, with 0 to 10 amino acid modifications, such as 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid modifications.;

[0028] Disclosed herein is an antibody or antigen-binding fragment thereof, comprising a heavy chain variable region (HCVR) and a light chain variable region (LCVR), wherein: (a) the HCVR comprises a heavy chain complementary determining region 1 (CDRH1), CDRH2 and CDRH3, and wherein CDRH1, CDRH2 and CDRH3 comprise the sequences shown in SEQ ID NOs: 3, 41 and 70, respectively, each having 0 to 3 amino acid modifications, such as 0, 1, 2 or 3 modifications; and (b) the LCVR comprises a light chain complementary determining region 1 (CDRL1), CDRL2 and CDRL3, and wherein CDRL1, CDRL2 and CDRL3 comprise the sequences shown in SEQ ID NOs: 6, 67 and 8, respectively, each having 0 to 3 amino acid modifications, such as 0, 1, 2 or 3 modifications. In some embodiments, the HCVR comprises a heavy chain complementary determining region 1 (CDRH1), CDRH2, and CDRH3, and wherein CDRH1, CDRH2, and CDRH3 comprise the sequences shown in SEQ ID NOs: 3, 41, and 70, respectively, each with 0 to 2 amino acid modifications. In some embodiments, the HCVR comprises a heavy chain complementary determining region 1 (CDRH1), CDRH2, and CDRH3, and wherein CDRH1, CDRH2, and CDRH3 comprise the sequences shown in SEQ ID NOs: 3, 41, and 70, respectively, each with 0 to 1 amino acid modifications. In some embodiments, the HCVR comprises a heavy chain complementary determining region 1 (CDRH1), CDRH2, and CDRH3, and wherein CDRH1, CDRH2, and CDRH3 comprise the sequences shown in SEQ ID NOs: 3, 41, and 70, respectively. In some embodiments, the LCVR comprises a light chain complementary determining region 1 (CDRL1), CDRL2, and CDRL3, and wherein CDRL1, CDRL2, and CDRL3 comprise a sequence as set forth in SEQ ID NOs: 6, 67, and 8, respectively, each with 0 to 2 amino acid modifications. In some embodiments, the LCVR comprises a light chain complementary determining region 1 (CDRL1), CDRL2, and CDRL3, and wherein CDRL1, CDRL2, and CDRL3 comprise a sequence as set forth in SEQ ID NOs: 6, 67, and 8, respectively, each with 0 to 1 amino acid modifications. In some embodiments, the LCVR comprises a light chain complementary determining region 1 (CDRL1), CDRL2, and CDRL3, and wherein CDRL1, CDRL2, and CDRL3 comprise a sequence as set forth in SEQ ID NOs: 6, 67, and 8, respectively.In some embodiments, the antibody or antigen-binding fragment thereof comprises a HCVR and a LCVR, the HCVR comprising a heavy chain complementary determining region 1 (CDRH1), CDRH2, and CDRH3, and wherein CDRH1, CDRH2, and CDRH3 comprise the sequences set forth in SEQ ID NOs: 3, 41, and 70, respectively, and the LCVR comprises a light chain complementary determining region 1 (CDRL1), CDRL2, and CDRL3, and wherein CDRL1, CDRL2, and CDRL3 comprise the sequences set forth in SEQ ID NOs: 6, 67, and 8, respectively. In some embodiments, the HCVR comprises an amino acid sequence having at least 90%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to the amino acid sequence set forth in SEQ ID NO: 72. In some embodiments, the HCVR comprises an amino acid sequence having at least 95% sequence identity to the amino acid sequence set forth in SEQ ID NO: 72. In some embodiments, the HCVR comprises an amino acid sequence having at least 97% sequence identity to the amino acid sequence set forth in SEQ ID NO: 72. In some embodiments, the HCVR comprises an amino acid sequence having at least 98% sequence identity to the amino acid sequence set forth in SEQ ID NO:72. In some embodiments, the HCVR comprises an amino acid sequence having at least 99% sequence identity to the amino acid sequence set forth in SEQ ID NO:72. In some embodiments, the HCVR comprises an amino acid sequence having 100% sequence identity to the amino acid sequence set forth in SEQ ID NO:72. In some embodiments, the LCVR comprises an amino acid sequence having at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence set forth in SEQ ID NO:65. In some embodiments, the LCVR comprises an amino acid sequence having at least 95% sequence identity to the amino acid sequence set forth in SEQ ID NO:65. In some embodiments, the LCVR comprises an amino acid sequence having at least 97% sequence identity to the amino acid sequence set forth in SEQ ID NO:65. In some embodiments, the LCVR comprises an amino acid sequence having at least 98% sequence identity to the amino acid sequence set forth in SEQ ID NO:65. In some embodiments, the LCVR comprises an amino acid sequence having at least 99% sequence identity to the amino acid sequence set forth in SEQ ID NO: 65. In some embodiments, the LCVR comprises an amino acid sequence having 100% sequence identity to the amino acid sequence set forth in SEQ ID NO: 65.In some embodiments, the HCVR comprises an amino acid sequence as set forth in SEQ ID NO: 72, with 0 to 10 amino acid modifications, such as 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid modifications. In some embodiments, the HCVR comprises an amino acid sequence as set forth in SEQ ID NO: 72, with 0 to 9 amino acid modifications. In some embodiments, the HCVR comprises an amino acid sequence as set forth in SEQ ID NO: 72, with 0 to 8 amino acid modifications. In some embodiments, the HCVR comprises an amino acid sequence as set forth in SEQ ID NO: 72, with 0 to 7 amino acid modifications. In some embodiments, the HCVR comprises an amino acid sequence as set forth in SEQ ID NO: 72, with 0 to 6 amino acid modifications. In some embodiments, the HCVR comprises an amino acid sequence as set forth in SEQ ID NO: 72, with 0 to 5 amino acid modifications. In some embodiments, the HCVR comprises an amino acid sequence as set forth in SEQ ID NO: 72, with 0 to 4 amino acid modifications. In some embodiments, the HCVR comprises an amino acid sequence as set forth in SEQ ID NO: 72, with 0 to 3 amino acid modifications. In some embodiments, the HCVR comprises the amino acid sequence as set forth in SEQ ID NO:72, with 0 to 2 amino acid modifications. In some embodiments, the HCVR comprises the amino acid sequence as set forth in SEQ ID NO:72, with 0 to 1 amino acid modification. In some embodiments, the HCVR comprises the amino acid sequence as set forth in SEQ ID NO:72. In some embodiments, the LCVR comprises the amino acid sequence as set forth in SEQ ID NO:65, with 0 to 10 amino acid modifications, such as 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid modifications. In some embodiments, the LCVR comprises the amino acid sequence as set forth in SEQ ID NO:65, with 0 to 9 amino acid modifications. In some embodiments, the LCVR comprises the amino acid sequence as set forth in SEQ ID NO:65, with 0 to 8 amino acid modifications. In some embodiments, the LCVR comprises the amino acid sequence as set forth in SEQ ID NO:65, with 0 to 7 amino acid modifications. In some embodiments, the LCVR comprises the amino acid sequence as set forth in SEQ ID NO:65, with 0 to 6 amino acid modifications. In some embodiments, the LCVR comprises the amino acid sequence as set forth in SEQ ID NO: 65, with 0 to 5 amino acid modifications. In some embodiments, the LCVR comprises the amino acid sequence as set forth in SEQ ID NO: 65, with 0 to 4 amino acid modifications. In some embodiments, the LCVR comprises the amino acid sequence as set forth in SEQ ID NO: 65, with 0 to 3 amino acid modifications.In some embodiments, the LCVR comprises the amino acid sequence as set forth in SEQ ID NO:65, with 0 to 2 amino acid modifications. In some embodiments, the LCVR comprises the amino acid sequence as set forth in SEQ ID NO:65, with 0 to 1 amino acid modifications. In some embodiments, the LCVR comprises the amino acid sequence as set forth in SEQ ID NO:65.

[0029] Disclosed herein is an antibody or antigen-binding fragment thereof, comprising a heavy chain variable region (HCVR) and a light chain variable region (LCVR), wherein: (a) the HCVR comprises a heavy chain complementary determining region 1 (CDRH1), CDRH2 and CDRH3, and wherein CDRH1, CDRH2 and CDRH3 comprise the sequences shown in SEQ ID NOs: 3, 41 and 5, respectively, each having 0 to 3 amino acid modifications, such as 0, 1, 2 or 3 modifications; and (b) the LCVR comprises a light chain complementary determining region 1 (CDRL1), CDRL2 and CDRL3, and wherein CDRL1, CDRL2 and CDRL3 comprise the sequences shown in SEQ ID NOs: 6, 67 and 8, respectively, each having 0 to 3 amino acid modifications, such as 0, 1, 2 or 3 modifications. In some embodiments, the HCVR comprises a heavy chain complementary determining region 1 (CDRH1), CDRH2, and CDRH3, and wherein CDRH1, CDRH2, and CDRH3 comprise the sequences shown in SEQ ID NOs: 3, 41, and 5, respectively, each with 0 to 2 amino acid modifications. In some embodiments, the HCVR comprises a heavy chain complementary determining region 1 (CDRH1), CDRH2, and CDRH3, and wherein CDRH1, CDRH2, and CDRH3 comprise the sequences shown in SEQ ID NOs: 3, 41, and 5, respectively, each with 0 to 1 amino acid modifications. In some embodiments, the HCVR comprises a heavy chain complementary determining region 1 (CDRH1), CDRH2, and CDRH3, and wherein CDRH1, CDRH2, and CDRH3 comprise the sequences shown in SEQ ID NOs: 3, 41, and 5, respectively. In some embodiments, the LCVR comprises a light chain complementary determining region 1 (CDRL1), CDRL2, and CDRL3, and wherein CDRL1, CDRL2, and CDRL3 comprise a sequence as set forth in SEQ ID NOs: 6, 67, and 8, respectively, each with 0 to 2 amino acid modifications. In some embodiments, the LCVR comprises a light chain complementary determining region 1 (CDRL1), CDRL2, and CDRL3, and wherein CDRL1, CDRL2, and CDRL3 comprise a sequence as set forth in SEQ ID NOs: 6, 67, and 8, respectively, each with 0 to 1 amino acid modifications. In some embodiments, the LCVR comprises a light chain complementary determining region 1 (CDRL1), CDRL2, and CDRL3, and wherein CDRL1, CDRL2, and CDRL3 comprise a sequence as set forth in SEQ ID NOs: 6, 67, and 8, respectively.In some embodiments, the antibody or antigen-binding fragment thereof comprises a HCVR comprising a heavy chain complementary determining region 1 (CDRH1), CDRH2, and CDRH3, and wherein CDRH1, CDRH2, and CDRH3 comprise the sequences set forth in SEQ ID NOs: 3, 41, and 5, respectively, and a LCVR comprising a light chain complementary determining region 1 (CDRL1), CDRL2, and CDRL3, and wherein CDRL1, CDRL2, and CDRL3 comprise the sequences set forth in SEQ ID NOs: 6, 67, and 8, respectively. In some embodiments, the HCVR comprises an amino acid sequence having at least 90%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to the amino acid sequence set forth in SEQ ID NO: 71. In some embodiments, the HCVR comprises an amino acid sequence having at least 95% sequence identity to the amino acid sequence set forth in SEQ ID NO: 71. In some embodiments, the HCVR comprises an amino acid sequence having at least 97% sequence identity to the amino acid sequence set forth in SEQ ID NO: 71. In some embodiments, the HCVR comprises an amino acid sequence having at least 98% sequence identity to the amino acid sequence set forth in SEQ ID NO:71. In some embodiments, the HCVR comprises an amino acid sequence having at least 99% sequence identity to the amino acid sequence set forth in SEQ ID NO:71. In some embodiments, the HCVR comprises an amino acid sequence having 100% sequence identity to the amino acid sequence set forth in SEQ ID NO:71. In some embodiments, the LCVR comprises an amino acid sequence having at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence set forth in SEQ ID NO:65. In some embodiments, the LCVR comprises an amino acid sequence having at least 95% sequence identity to the amino acid sequence set forth in SEQ ID NO:65. In some embodiments, the LCVR comprises an amino acid sequence having at least 97% sequence identity to the amino acid sequence set forth in SEQ ID NO:65. In some embodiments, the LCVR comprises an amino acid sequence having at least 98% sequence identity to the amino acid sequence set forth in SEQ ID NO:65. In some embodiments, the LCVR comprises an amino acid sequence having at least 99% sequence identity to the amino acid sequence set forth in SEQ ID NO: 65. In some embodiments, the LCVR comprises an amino acid sequence having 100% sequence identity to the amino acid sequence set forth in SEQ ID NO: 65.In some embodiments, the HCVR comprises an amino acid sequence as set forth in SEQ ID NO: 71, with 0 to 10 amino acid modifications, such as 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid modifications. In some embodiments, the HCVR comprises an amino acid sequence as set forth in SEQ ID NO: 71, with 0 to 9 amino acid modifications. In some embodiments, the HCVR comprises an amino acid sequence as set forth in SEQ ID NO: 71, with 0 to 8 amino acid modifications. In some embodiments, the HCVR comprises an amino acid sequence as set forth in SEQ ID NO: 71, with 0 to 7 amino acid modifications. In some embodiments, the HCVR comprises an amino acid sequence as set forth in SEQ ID NO: 71, with 0 to 6 amino acid modifications. In some embodiments, the HCVR comprises an amino acid sequence as set forth in SEQ ID NO: 71, with 0 to 5 amino acid modifications. In some embodiments, the HCVR comprises an amino acid sequence as set forth in SEQ ID NO: 71, with 0 to 4 amino acid modifications. In some embodiments, the HCVR comprises an amino acid sequence as set forth in SEQ ID NO: 71, with 0 to 3 amino acid modifications. In some embodiments, the HCVR comprises the amino acid sequence as set forth in SEQ ID NO:71, with 0 to 2 amino acid modifications. In some embodiments, the HCVR comprises the amino acid sequence as set forth in SEQ ID NO:71, with 0 to 1 amino acid modification. In some embodiments, the HCVR comprises the amino acid sequence as set forth in SEQ ID NO:71. In some embodiments, the LCVR comprises the amino acid sequence as set forth in SEQ ID NO:65, with 0 to 10 amino acid modifications, such as 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid modifications. In some embodiments, the LCVR comprises the amino acid sequence as set forth in SEQ ID NO:65, with 0 to 9 amino acid modifications. In some embodiments, the LCVR comprises the amino acid sequence as set forth in SEQ ID NO:65, with 0 to 8 amino acid modifications. In some embodiments, the LCVR comprises the amino acid sequence as set forth in SEQ ID NO:65, with 0 to 7 amino acid modifications. In some embodiments, the LCVR comprises the amino acid sequence as set forth in SEQ ID NO:65, with 0 to 6 amino acid modifications. In some embodiments, the LCVR comprises the amino acid sequence as set forth in SEQ ID NO: 65, with 0 to 5 amino acid modifications. In some embodiments, the LCVR comprises the amino acid sequence as set forth in SEQ ID NO: 65, with 0 to 4 amino acid modifications. In some embodiments, the LCVR comprises the amino acid sequence as set forth in SEQ ID NO: 65, with 0 to 3 amino acid modifications.In some embodiments, the LCVR comprises the amino acid sequence as set forth in SEQ ID NO:65, with 0 to 2 amino acid modifications. In some embodiments, the LCVR comprises the amino acid sequence as set forth in SEQ ID NO:65, with 0 to 1 amino acid modifications. In some embodiments, the LCVR comprises the amino acid sequence as set forth in SEQ ID NO:65.

[0030] Disclosed herein is an antibody or antigen-binding fragment thereof, comprising (a) a heavy chain comprising a heavy chain variable region (HCVR), wherein the HCVR comprises 1 to 3 heavy chain CDRs as shown in any one of SEQ ID NOs: 3, 4, 41, 5, 69 or 70 with 0 to 3 amino acid modifications; and (b) a light chain comprising a light chain variable region (LCVR), wherein the LCVR comprises 1 to 3 light chain CDRs as shown in any one of SEQ ID NOs: 6, 67 or 8 with 0 to 3 amino acid modifications.

[0031] Disclosed herein is an antibody or antigen-binding fragment thereof, comprising (a) a heavy chain comprising a heavy chain variable region (HCVR), wherein the HCVR comprises 1 to 3 heavy chain CDRs as shown in any one of SEQ ID NOs: 3, 4, 41, 5, 69 or 70 with 0 to 3 amino acid modifications; and (b) a light chain comprising a light chain variable region (LCVR), wherein the LCVR comprises 1 to 3 light chain CDRs as shown in any one of SEQ ID NOs: 6, 7 or 8 with 0 to 3 amino acid modifications.

[0032] Disclosed herein is an antibody or antigen-binding fragment thereof, comprising (a) a heavy chain comprising a heavy chain variable region (HCVR), wherein the HCVR comprises 1 to 3 heavy chain CDRs as shown in any one of SEQ ID NOs: 3, 4, 41, 5, 69 or 70 with 0 to 3 amino acid modifications; and (b) a light chain comprising a light chain variable region (LCVR), wherein the LCVR comprises 1 to 3 light chain CDRs as shown in any one of SEQ ID NOs: 6, 68 or 8 with 0 to 3 amino acid modifications.

[0033] Disclosed herein is an antibody or antigen-binding fragment thereof, comprising (a) a heavy chain comprising a heavy chain variable region (HCVR), wherein the HCVR comprises a heavy chain complementary determining region 1 (CDRH1), CDRH2, and CDRH3, and wherein CDRH1, CDRH2, and CDRH3 comprise the sequences shown in SEQ ID NOs: 3, 4, and 5, respectively, with 0 to 3 amino acid modifications; and (b) a light chain comprising a light chain variable region (LCVR), wherein the LCVR comprises a light chain complementary determining region 1 (CDRL1), CDRL2, and CDRL3, and wherein CDRL1, CDRL2, and CDRL3 comprise the sequences shown in SEQ ID NOs: 6, 7, and 8, respectively, with 0 to 3 amino acid modifications. In some embodiments, the HCVR comprises an amino acid sequence having at least 90%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to the amino acid sequence shown in SEQ ID NO: 1. In some embodiments, the HCVR comprises an amino acid sequence having at least 95% sequence identity to the amino acid sequence set forth in SEQ ID NO: 1. In some embodiments, the HCVR comprises an amino acid sequence having at least 97% sequence identity to the amino acid sequence set forth in SEQ ID NO: 1. In some embodiments, the HCVR comprises an amino acid sequence having at least 98% sequence identity to the amino acid sequence set forth in SEQ ID NO: 1. In some embodiments, the HCVR comprises an amino acid sequence having at least 99% sequence identity to the amino acid sequence set forth in SEQ ID NO: 1. In some embodiments, the HCVR comprises an amino acid sequence having 100% sequence identity to the amino acid sequence set forth in SEQ ID NO: 1. In some embodiments, the LCVR comprises an amino acid sequence having at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence set forth in SEQ ID NO: 2. In some embodiments, the LCVR comprises an amino acid sequence having at least 95% sequence identity to the amino acid sequence set forth in SEQ ID NO: 2. In some embodiments, the LCVR comprises an amino acid sequence having at least 97% sequence identity to the amino acid sequence set forth in SEQ ID NO: 2. In some embodiments, the LCVR comprises an amino acid sequence having at least 98% sequence identity to the amino acid sequence set forth in SEQ ID NO: 2. In some embodiments, the LCVR comprises an amino acid sequence having at least 99% sequence identity to the amino acid sequence set forth in SEQ ID NO: 2. In some embodiments, the LCVR comprises an amino acid sequence having 100% sequence identity to the amino acid sequence set forth in SEQ ID NO: 2.In some embodiments, the HCVR comprises the amino acid sequence as set forth in SEQ ID NO: 1, with 0 to 10 amino acid modifications, such as 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid modifications. In some embodiments, the HCVR comprises the amino acid sequence as set forth in SEQ ID NO: 1, with 0 to 9 amino acid modifications. In some embodiments, the HCVR comprises the amino acid sequence as set forth in SEQ ID NO: 1, with 0 to 8 amino acid modifications. In some embodiments, the HCVR comprises the amino acid sequence as set forth in SEQ ID NO: 1, with 0 to 7 amino acid modifications. In some embodiments, the HCVR comprises the amino acid sequence as set forth in SEQ ID NO: 1, with 0 to 6 amino acid modifications. In some embodiments, the HCVR comprises the amino acid sequence as set forth in SEQ ID NO: 1, with 0 to 5 amino acid modifications. In some embodiments, the HCVR comprises the amino acid sequence as set forth in SEQ ID NO: 1, with 0 to 4 amino acid modifications. In some embodiments, the HCVR comprises the amino acid sequence as set forth in SEQ ID NO: 1, with 0 to 3 amino acid modifications. In some embodiments, the HCVR comprises the amino acid sequence as set forth in SEQ ID NO: 1, with 0 to 2 amino acid modifications. In some embodiments, the HCVR comprises the amino acid sequence as set forth in SEQ ID NO: 1, with 0 to 1 amino acid modification. In some embodiments, the HCVR comprises the amino acid sequence as set forth in SEQ ID NO: 1. In some embodiments, the LCVR comprises the amino acid sequence as set forth in SEQ ID NO: 2, with 0 to 10 amino acid modifications, such as 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid modifications. In some embodiments, the LCVR comprises the amino acid sequence as set forth in SEQ ID NO: 2, with 0 to 9 amino acid modifications. In some embodiments, the LCVR comprises the amino acid sequence as set forth in SEQ ID NO: 2, with 0 to 8 amino acid modifications. In some embodiments, the LCVR comprises the amino acid sequence as set forth in SEQ ID NO: 2, with 0 to 7 amino acid modifications. In some embodiments, the LCVR comprises the amino acid sequence as set forth in SEQ ID NO: 2, with 0 to 6 amino acid modifications. In some embodiments, the LCVR comprises the amino acid sequence as set forth in SEQ ID NO: 2, with 0 to 5 amino acid modifications. In some embodiments, the LCVR comprises the amino acid sequence as set forth in SEQ ID NO: 2, with 0 to 4 amino acid modifications. In some embodiments, the LCVR comprises the amino acid sequence as set forth in SEQ ID NO: 2, with 0 to 3 amino acid modifications.In some embodiments, the LCVR comprises the amino acid sequence as set forth in SEQ ID NO: 2, with 0 to 2 amino acid modifications. In some embodiments, the LCVR comprises the amino acid sequence as set forth in SEQ ID NO: 2, with 0 to 1 amino acid modifications. In some embodiments, the LCVR comprises the amino acid sequence as set forth in SEQ ID NO: 2.

[0034] Disclosed herein is an antibody or antigen-binding fragment thereof, comprising (a) a heavy chain comprising a heavy chain variable region (HCVR), wherein the HCVR comprises a heavy chain complementary determining region 1 (CDRH1), CDRH2, and CDRH3, and wherein CDRH1, CDRH2, and CDRH3 comprise a sequence as shown in SEQ ID NO: 11, 12, or 13, respectively, with 0 to 3 amino acid modifications; and (b) a light chain comprising a light chain variable region (LCVR), wherein the LCVR comprises a light chain complementary determining region 1 (CDRL1), CDRL2, and CDRL3, and wherein CDRL1, CDRL2, and CDRL3 comprise a sequence as shown in SEQ ID NO: 14, 15, or 16, respectively, with 0 to 3 amino acid modifications. In some embodiments, the HCVR comprises an amino acid sequence having at least 90%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to the amino acid sequence as shown in SEQ ID NO: 9. In some embodiments, the HCVR comprises an amino acid sequence having at least 95% sequence identity to the amino acid sequence set forth in SEQ ID NO:9. In some embodiments, the HCVR comprises an amino acid sequence having at least 97% sequence identity to the amino acid sequence set forth in SEQ ID NO:9. In some embodiments, the HCVR comprises an amino acid sequence having at least 98% sequence identity to the amino acid sequence set forth in SEQ ID NO:9. In some embodiments, the HCVR comprises an amino acid sequence having at least 99% sequence identity to the amino acid sequence set forth in SEQ ID NO:9. In some embodiments, the HCVR comprises an amino acid sequence having 100% sequence identity to the amino acid sequence set forth in SEQ ID NO:9. In some embodiments, the LCVR comprises an amino acid sequence having at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence set forth in SEQ ID NO:10. In some embodiments, the LCVR comprises an amino acid sequence having at least 95% sequence identity to the amino acid sequence set forth in SEQ ID NO:10. In some embodiments, the LCVR comprises an amino acid sequence having at least 97% sequence identity to the amino acid sequence set forth in SEQ ID NO: 10. In some embodiments, the LCVR comprises an amino acid sequence having at least 98% sequence identity to the amino acid sequence set forth in SEQ ID NO: 10. In some embodiments, the LCVR comprises an amino acid sequence having at least 99% sequence identity to the amino acid sequence set forth in SEQ ID NO: 10. In some embodiments, the LCVR comprises an amino acid sequence having 100% sequence identity to the amino acid sequence set forth in SEQ ID NO: 10.In some embodiments, the HCVR comprises an amino acid sequence as set forth in SEQ ID NO: 9, with 0 to 10 amino acid modifications, such as 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid modifications. In some embodiments, the HCVR comprises an amino acid sequence as set forth in SEQ ID NO: 9, with 0 to 9 amino acid modifications. In some embodiments, the HCVR comprises an amino acid sequence as set forth in SEQ ID NO: 9, with 0 to 8 amino acid modifications. In some embodiments, the HCVR comprises an amino acid sequence as set forth in SEQ ID NO: 9, with 0 to 7 amino acid modifications. In some embodiments, the HCVR comprises an amino acid sequence as set forth in SEQ ID NO: 9, with 0 to 6 amino acid modifications. In some embodiments, the HCVR comprises an amino acid sequence as set forth in SEQ ID NO: 9, with 0 to 5 amino acid modifications. In some embodiments, the HCVR comprises an amino acid sequence as set forth in SEQ ID NO: 9, with 0 to 4 amino acid modifications. In some embodiments, the HCVR comprises an amino acid sequence as set forth in SEQ ID NO: 9, with 0 to 3 amino acid modifications. In some embodiments, the HCVR comprises the amino acid sequence as set forth in SEQ ID NO:9, with 0 to 2 amino acid modifications. In some embodiments, the HCVR comprises the amino acid sequence as set forth in SEQ ID NO:9, with 0 to 1 amino acid modification. In some embodiments, the HCVR comprises the amino acid sequence as set forth in SEQ ID NO:9. In some embodiments, the LCVR comprises the amino acid sequence as set forth in SEQ ID NO:10, with 0 to 10 amino acid modifications, such as 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid modifications. In some embodiments, the LCVR comprises the amino acid sequence as set forth in SEQ ID NO:10, with 0 to 9 amino acid modifications. In some embodiments, the LCVR comprises the amino acid sequence as set forth in SEQ ID NO:10, with 0 to 8 amino acid modifications. In some embodiments, the LCVR comprises the amino acid sequence as set forth in SEQ ID NO:10, with 0 to 7 amino acid modifications. In some embodiments, the LCVR comprises the amino acid sequence as set forth in SEQ ID NO:10, with 0 to 6 amino acid modifications. In some embodiments, the LCVR comprises the amino acid sequence as set forth in SEQ ID NO: 10, with 0 to 5 amino acid modifications. In some embodiments, the LCVR comprises the amino acid sequence as set forth in SEQ ID NO: 10, with 0 to 4 amino acid modifications. In some embodiments, the LCVR comprises the amino acid sequence as set forth in SEQ ID NO: 10, with 0 to 3 amino acid modifications.In some embodiments, the LCVR comprises the amino acid sequence as set forth in SEQ ID NO: 10, with 0 to 2 amino acid modifications. In some embodiments, the LCVR comprises the amino acid sequence as set forth in SEQ ID NO: 10, with 0 to 1 amino acid modifications. In some embodiments, the LCVR comprises the amino acid sequence as set forth in SEQ ID NO: 10.

[0035] Disclosed herein is an antibody or antigen-binding fragment thereof, comprising (a) a heavy chain comprising a heavy chain variable region (HCVR), wherein the HCVR comprises a heavy chain complementary determining region 1 (CDRH1), CDRH2, and CDRH3, and wherein CDRH1, CDRH2, and CDRH3 comprise a sequence as shown in SEQ ID NO: 19, 20, or 21, respectively, with 0 to 3 amino acid modifications; and (b) a light chain comprising a light chain variable region (LCVR), wherein the LCVR comprises a light chain complementary determining region 1 (CDRL1), CDRL2, and CDRL3, and wherein CDRL1, CDRL2, and CDRL3 comprise a sequence as shown in SEQ ID NO: 22, 23, or 24, respectively, with 0 to 3 amino acid modifications. In some embodiments, the HCVR comprises an amino acid sequence having at least 90%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to the amino acid sequence as shown in SEQ ID NO: 17. In some embodiments, the HCVR comprises an amino acid sequence having at least 95% sequence identity to the amino acid sequence set forth in SEQ ID NO: 17. In some embodiments, the HCVR comprises an amino acid sequence having at least 97% sequence identity to the amino acid sequence set forth in SEQ ID NO: 17. In some embodiments, the HCVR comprises an amino acid sequence having at least 98% sequence identity to the amino acid sequence set forth in SEQ ID NO: 17. In some embodiments, the HCVR comprises an amino acid sequence having at least 99% sequence identity to the amino acid sequence set forth in SEQ ID NO: 17. In some embodiments, the HCVR comprises an amino acid sequence having 100% sequence identity to the amino acid sequence set forth in SEQ ID NO: 17. In some embodiments, the LCVR comprises an amino acid sequence having at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence set forth in SEQ ID NO: 18. In some embodiments, the LCVR comprises an amino acid sequence having at least 95% sequence identity to the amino acid sequence set forth in SEQ ID NO: 18. In some embodiments, the LCVR comprises an amino acid sequence having at least 97% sequence identity to the amino acid sequence set forth in SEQ ID NO: 18. In some embodiments, the LCVR comprises an amino acid sequence having at least 98% sequence identity to the amino acid sequence set forth in SEQ ID NO: 18. In some embodiments, the LCVR comprises an amino acid sequence having at least 99% sequence identity to the amino acid sequence set forth in SEQ ID NO: 18. In some embodiments, the LCVR comprises an amino acid sequence having 100% sequence identity to the amino acid sequence set forth in SEQ ID NO: 18.In some embodiments, the HCVR comprises an amino acid sequence as set forth in SEQ ID NO: 17, with 0 to 10 amino acid modifications, such as 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid modifications. In some embodiments, the HCVR comprises an amino acid sequence as set forth in SEQ ID NO: 17, with 0 to 9 amino acid modifications. In some embodiments, the HCVR comprises an amino acid sequence as set forth in SEQ ID NO: 17, with 0 to 8 amino acid modifications. In some embodiments, the HCVR comprises an amino acid sequence as set forth in SEQ ID NO: 17, with 0 to 7 amino acid modifications. In some embodiments, the HCVR comprises an amino acid sequence as set forth in SEQ ID NO: 17, with 0 to 6 amino acid modifications. In some embodiments, the HCVR comprises an amino acid sequence as set forth in SEQ ID NO: 17, with 0 to 5 amino acid modifications. In some embodiments, the HCVR comprises an amino acid sequence as set forth in SEQ ID NO: 17, with 0 to 4 amino acid modifications. In some embodiments, the HCVR comprises an amino acid sequence as set forth in SEQ ID NO: 17, with 0 to 3 amino acid modifications. In some embodiments, the HCVR comprises the amino acid sequence as set forth in SEQ ID NO: 17, with 0 to 2 amino acid modifications. In some embodiments, the HCVR comprises the amino acid sequence as set forth in SEQ ID NO: 17, with 0 to 1 amino acid modification. In some embodiments, the HCVR comprises the amino acid sequence as set forth in SEQ ID NO: 17. In some embodiments, the LCVR comprises the amino acid sequence as set forth in SEQ ID NO: 18, with 0 to 10 amino acid modifications, such as 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid modifications. In some embodiments, the LCVR comprises the amino acid sequence as set forth in SEQ ID NO: 18, with 0 to 9 amino acid modifications. In some embodiments, the LCVR comprises the amino acid sequence as set forth in SEQ ID NO: 18, with 0 to 8 amino acid modifications. In some embodiments, the LCVR comprises the amino acid sequence as set forth in SEQ ID NO: 18, with 0 to 7 amino acid modifications. In some embodiments, the LCVR comprises the amino acid sequence as set forth in SEQ ID NO: 18, with 0 to 6 amino acid modifications. In some embodiments, the LCVR comprises the amino acid sequence as set forth in SEQ ID NO: 18, with 0 to 5 amino acid modifications. In some embodiments, the LCVR comprises the amino acid sequence as set forth in SEQ ID NO: 18, with 0 to 4 amino acid modifications. In some embodiments, the LCVR comprises the amino acid sequence as set forth in SEQ ID NO: 18, with 0 to 3 amino acid modifications.In some embodiments, the LCVR comprises the amino acid sequence as set forth in SEQ ID NO: 18, with 0 to 2 amino acid modifications. In some embodiments, the LCVR comprises the amino acid sequence as set forth in SEQ ID NO: 18, with 0 to 1 amino acid modifications. In some embodiments, the LCVR comprises the amino acid sequence as set forth in SEQ ID NO: 18.

[0036] Disclosed herein is an antibody or antigen-binding fragment thereof, comprising (a) a heavy chain comprising a heavy chain variable region (HCVR), wherein the HCVR comprises a heavy chain complementary determining region 1 (CDRH1), CDRH2, and CDRH3, and wherein CDRH1, CDRH2, and CDRH3 comprise a sequence as shown in SEQ ID NO: 27, 28, or 29, respectively, with 0 to 3 amino acid modifications; and (b) a light chain comprising a light chain variable region (LCVR), wherein the LCVR comprises a light chain complementary determining region 1 (CDRL1), CDRL2, and CDRL3, and wherein CDRL1, CDRL2, and CDRL3 comprise a sequence as shown in SEQ ID NO: 30, 31, or 32, respectively, with 0 to 3 amino acid modifications. In some embodiments, the HCVR comprises an amino acid sequence having at least 90%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to the amino acid sequence as shown in SEQ ID NO: 25. In some embodiments, the HCVR comprises an amino acid sequence having at least 95% sequence identity to the amino acid sequence set forth in SEQ ID NO:25. In some embodiments, the HCVR comprises an amino acid sequence having at least 97% sequence identity to the amino acid sequence set forth in SEQ ID NO:25. In some embodiments, the HCVR comprises an amino acid sequence having at least 98% sequence identity to the amino acid sequence set forth in SEQ ID NO:25. In some embodiments, the HCVR comprises an amino acid sequence having at least 99% sequence identity to the amino acid sequence set forth in SEQ ID NO:25. In some embodiments, the HCVR comprises an amino acid sequence having 100% sequence identity to the amino acid sequence set forth in SEQ ID NO:25. In some embodiments, the LCVR comprises an amino acid sequence having at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence set forth in SEQ ID NO:26. In some embodiments, the LCVR comprises an amino acid sequence having at least 95% sequence identity to the amino acid sequence set forth in SEQ ID NO:26. In some embodiments, the LCVR comprises an amino acid sequence having at least 97% sequence identity to the amino acid sequence set forth in SEQ ID NO: 26. In some embodiments, the LCVR comprises an amino acid sequence having at least 98% sequence identity to the amino acid sequence set forth in SEQ ID NO: 26. In some embodiments, the LCVR comprises an amino acid sequence having at least 99% sequence identity to the amino acid sequence set forth in SEQ ID NO: 26. In some embodiments, the LCVR comprises an amino acid sequence having 100% sequence identity to the amino acid sequence set forth in SEQ ID NO: 26.In some embodiments, the HCVR comprises an amino acid sequence as set forth in SEQ ID NO: 25, with 0 to 10 amino acid modifications, such as 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid modifications. In some embodiments, the HCVR comprises an amino acid sequence as set forth in SEQ ID NO: 25, with 0 to 9 amino acid modifications. In some embodiments, the HCVR comprises an amino acid sequence as set forth in SEQ ID NO: 25, with 0 to 8 amino acid modifications. In some embodiments, the HCVR comprises an amino acid sequence as set forth in SEQ ID NO: 25, with 0 to 7 amino acid modifications. In some embodiments, the HCVR comprises an amino acid sequence as set forth in SEQ ID NO: 25, with 0 to 6 amino acid modifications. In some embodiments, the HCVR comprises an amino acid sequence as set forth in SEQ ID NO: 25, with 0 to 5 amino acid modifications. In some embodiments, the HCVR comprises an amino acid sequence as set forth in SEQ ID NO: 25, with 0 to 4 amino acid modifications. In some embodiments, the HCVR comprises an amino acid sequence as set forth in SEQ ID NO: 25, with 0 to 3 amino acid modifications. In some embodiments, the HCVR comprises the amino acid sequence as set forth in SEQ ID NO:25, with 0 to 2 amino acid modifications. In some embodiments, the HCVR comprises the amino acid sequence as set forth in SEQ ID NO:25, with 0 to 1 amino acid modification. In some embodiments, the HCVR comprises the amino acid sequence as set forth in SEQ ID NO:25. In some embodiments, the LCVR comprises the amino acid sequence as set forth in SEQ ID NO:26, with 0 to 10 amino acid modifications, such as 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid modifications. In some embodiments, the LCVR comprises the amino acid sequence as set forth in SEQ ID NO:26, with 0 to 9 amino acid modifications. In some embodiments, the LCVR comprises the amino acid sequence as set forth in SEQ ID NO:26, with 0 to 8 amino acid modifications. In some embodiments, the LCVR comprises the amino acid sequence as set forth in SEQ ID NO:26, with 0 to 7 amino acid modifications. In some embodiments, the LCVR comprises the amino acid sequence as set forth in SEQ ID NO:26, with 0 to 6 amino acid modifications. In some embodiments, the LCVR comprises the amino acid sequence as set forth in SEQ ID NO: 26, with 0 to 5 amino acid modifications. In some embodiments, the LCVR comprises the amino acid sequence as set forth in SEQ ID NO: 26, with 0 to 4 amino acid modifications. In some embodiments, the LCVR comprises the amino acid sequence as set forth in SEQ ID NO: 26, with 0 to 3 amino acid modifications.In some embodiments, the LCVR comprises the amino acid sequence as set forth in SEQ ID NO: 26, with 0 to 2 amino acid modifications. In some embodiments, the LCVR comprises the amino acid sequence as set forth in SEQ ID NO: 26, with 0 to 1 amino acid modifications. In some embodiments, the LCVR comprises the amino acid sequence as set forth in SEQ ID NO: 26.

[0037] Disclosed herein is an antibody or antigen-binding fragment thereof, comprising (a) a heavy chain comprising a heavy chain variable region (HCVR), wherein the HCVR comprises a heavy chain complementary determining region 1 (CDRH1), CDRH2, and CDRH3, and wherein CDRH1, CDRH2, and CDRH3 comprise a sequence as shown in SEQ ID NO: 35, 36, or 37, respectively, with 0 to 3 amino acid modifications; and (b) a light chain comprising a light chain variable region (LCVR), wherein the LCVR comprises a light chain complementary determining region 1 (CDRL1), CDRL2, and CDRL3, and wherein CDRL1, CDRL2, and CDRL3 comprise a sequence as shown in SEQ ID NO: 38, 39, or 40, respectively, with 0 to 3 amino acid modifications. In some embodiments, the HCVR comprises an amino acid sequence having at least 90%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to the amino acid sequence as shown in SEQ ID NO: 33. In some embodiments, the HCVR comprises an amino acid sequence having at least 95% sequence identity to the amino acid sequence set forth in SEQ ID NO:33. In some embodiments, the HCVR comprises an amino acid sequence having at least 97% sequence identity to the amino acid sequence set forth in SEQ ID NO:33. In some embodiments, the HCVR comprises an amino acid sequence having at least 98% sequence identity to the amino acid sequence set forth in SEQ ID NO:33. In some embodiments, the HCVR comprises an amino acid sequence having at least 99% sequence identity to the amino acid sequence set forth in SEQ ID NO:33. In some embodiments, the HCVR comprises an amino acid sequence having 100% sequence identity to the amino acid sequence set forth in SEQ ID NO:33. In some embodiments, the LCVR comprises an amino acid sequence having at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence set forth in SEQ ID NO:34. In some embodiments, the LCVR comprises an amino acid sequence having at least 95% sequence identity to the amino acid sequence set forth in SEQ ID NO:34. In some embodiments, the LCVR comprises an amino acid sequence having at least 97% sequence identity to the amino acid sequence set forth in SEQ ID NO: 34. In some embodiments, the LCVR comprises an amino acid sequence having at least 98% sequence identity to the amino acid sequence set forth in SEQ ID NO: 34. In some embodiments, the LCVR comprises an amino acid sequence having at least 99% sequence identity to the amino acid sequence set forth in SEQ ID NO: 34. In some embodiments, the LCVR comprises an amino acid sequence having 100% sequence identity to the amino acid sequence set forth in SEQ ID NO: 34.In some embodiments, the HCVR comprises an amino acid sequence as set forth in SEQ ID NO: 33, with 0 to 10 amino acid modifications, such as 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid modifications. In some embodiments, the HCVR comprises an amino acid sequence as set forth in SEQ ID NO: 33, with 0 to 9 amino acid modifications. In some embodiments, the HCVR comprises an amino acid sequence as set forth in SEQ ID NO: 33, with 0 to 8 amino acid modifications. In some embodiments, the HCVR comprises an amino acid sequence as set forth in SEQ ID NO: 33, with 0 to 7 amino acid modifications. In some embodiments, the HCVR comprises an amino acid sequence as set forth in SEQ ID NO: 33, with 0 to 6 amino acid modifications. In some embodiments, the HCVR comprises an amino acid sequence as set forth in SEQ ID NO: 33, with 0 to 5 amino acid modifications. In some embodiments, the HCVR comprises an amino acid sequence as set forth in SEQ ID NO: 33, with 0 to 4 amino acid modifications. In some embodiments, the HCVR comprises an amino acid sequence as set forth in SEQ ID NO: 33, with 0 to 3 amino acid modifications. In some embodiments, the HCVR comprises the amino acid sequence as set forth in SEQ ID NO:33, with 0 to 2 amino acid modifications. In some embodiments, the HCVR comprises the amino acid sequence as set forth in SEQ ID NO:33, with 0 to 1 amino acid modification. In some embodiments, the HCVR comprises the amino acid sequence as set forth in SEQ ID NO:33. In some embodiments, the LCVR comprises the amino acid sequence as set forth in SEQ ID NO:34, with 0 to 10 amino acid modifications, such as 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid modifications. In some embodiments, the LCVR comprises the amino acid sequence as set forth in SEQ ID NO:34, with 0 to 9 amino acid modifications. In some embodiments, the LCVR comprises the amino acid sequence as set forth in SEQ ID NO:34, with 0 to 8 amino acid modifications. In some embodiments, the LCVR comprises the amino acid sequence as set forth in SEQ ID NO:34, with 0 to 7 amino acid modifications. In some embodiments, the LCVR comprises the amino acid sequence as set forth in SEQ ID NO:34, with 0 to 6 amino acid modifications. In some embodiments, the LCVR comprises the amino acid sequence as set forth in SEQ ID NO: 34, with 0 to 5 amino acid modifications. In some embodiments, the LCVR comprises the amino acid sequence as set forth in SEQ ID NO: 34, with 0 to 4 amino acid modifications. In some embodiments, the LCVR comprises the amino acid sequence as set forth in SEQ ID NO: 34, with 0 to 3 amino acid modifications.In some embodiments, the LCVR comprises the amino acid sequence as set forth in SEQ ID NO:34, with 0 to 2 amino acid modifications. In some embodiments, the LCVR comprises the amino acid sequence as set forth in SEQ ID NO:34, with 0 to 1 amino acid modifications. In some embodiments, the LCVR comprises the amino acid sequence as set forth in SEQ ID NO:34.

[0038] In some embodiments, the LCVR is linked to a light chain constant region comprising an amino acid sequence having at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence set forth in SEQ ID NO: 62. In some embodiments, the LCVR is linked to a light chain constant region comprising an amino acid sequence having at least 95% sequence identity to the amino acid sequence set forth in SEQ ID NO: 62. In some embodiments, the LCVR is linked to a light chain constant region comprising an amino acid sequence having at least 97% sequence identity to the amino acid sequence set forth in SEQ ID NO: 62. In some embodiments, the LCVR is linked to a light chain constant region comprising an amino acid sequence having at least 98% sequence identity to the amino acid sequence set forth in SEQ ID NO: 62. In some embodiments, the LCVR is linked to a light chain constant region comprising an amino acid sequence having at least 99% sequence identity to the amino acid sequence set forth in SEQ ID NO: 62. In some embodiments, the LCVR is linked to a light chain constant region comprising an amino acid sequence having 100% sequence identity to the amino acid sequence set forth in SEQ ID NO:62.

[0039] In some embodiments, the light chain variable region is connected to a light chain constant region, and the light chain constant region comprises an amino acid sequence as shown in SEQ ID NO: 62, with 0 to 10 amino acid modifications, such as 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid modifications. In some embodiments, the light chain variable region is connected to a light chain constant region, and the light chain constant region comprises an amino acid sequence as shown in SEQ ID NO: 62 with 0 to 9 amino acid modifications. In some embodiments, the light chain variable region is connected to a light chain constant region, and the light chain constant region comprises an amino acid sequence as shown in SEQ ID NO: 62 with 0 to 8 amino acid modifications. In some embodiments, the light chain variable region is connected to a light chain constant region, and the light chain constant region comprises an amino acid sequence as shown in SEQ ID NO: 62 with 0 to 7 amino acid modifications. In some embodiments, the light chain variable region is connected to a light chain constant region, and the light chain constant region comprises an amino acid sequence as shown in SEQ ID NO: 62 with 0 to 6 amino acid modifications. In some embodiments, the light chain variable region is linked to a light chain constant region, which comprises an amino acid sequence as shown in SEQ ID NO: 62 with 0 to 5 amino acid modifications. In some embodiments, the light chain variable region is linked to a light chain constant region, which comprises an amino acid sequence as shown in SEQ ID NO: 62 with 0 to 4 amino acid modifications. In some embodiments, the light chain variable region is linked to a light chain constant region, which comprises an amino acid sequence as shown in SEQ ID NO: 62 with 0 to 3 amino acid modifications. In some embodiments, the light chain variable region is linked to a light chain constant region, which comprises an amino acid sequence as shown in SEQ ID NO: 62 with 0 to 2 amino acid modifications. In some embodiments, the light chain variable region is linked to a light chain constant region, which comprises an amino acid sequence as shown in SEQ ID NO: 62 with 0 to 1 amino acid modifications. In some embodiments, the light chain variable region is linked to a light chain constant region, which comprises an amino acid sequence as shown in SEQ ID NO: 62.

[0040] In some embodiments, the light chain variable region is linked to a light chain constant region, which comprises an amino acid sequence having at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity with the amino acid sequence shown in SEQ ID NO: 64. In some embodiments, the light chain variable region is linked to a light chain constant region, which comprises an amino acid sequence having at least 95% sequence identity with the amino acid sequence shown in SEQ ID NO: 64. In some embodiments, the light chain variable region is linked to a light chain constant region, which comprises an amino acid sequence having at least 97% sequence identity with the amino acid sequence shown in SEQ ID NO: 64. In some embodiments, the light chain variable region is linked to a light chain constant region, which comprises an amino acid sequence having at least 98% sequence identity with the amino acid sequence shown in SEQ ID NO: 64. In some embodiments, the light chain variable region is linked to a light chain constant region, which comprises an amino acid sequence having at least 99% sequence identity with the amino acid sequence shown in SEQ ID NO: 64. In some embodiments, the light chain variable region is linked to a light chain constant region comprising an amino acid sequence having 100% sequence identity to the amino acid sequence shown as SEQ ID NO:64.

[0041] In some embodiments, the light chain variable region is connected to a light chain constant region, and the light chain constant region comprises an amino acid sequence as shown in SEQ ID NO: 64, with 0 to 10 amino acid modifications, such as 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid modifications. In some embodiments, the light chain variable region is connected to a light chain constant region, and the light chain constant region comprises an amino acid sequence as shown in SEQ ID NO: 64 with 0 to 9 amino acid modifications. In some embodiments, the light chain variable region is connected to a light chain constant region, and the light chain constant region comprises an amino acid sequence as shown in SEQ ID NO: 64 with 0 to 8 amino acid modifications. In some embodiments, the light chain variable region is connected to a light chain constant region, and the light chain constant region comprises an amino acid sequence as shown in SEQ ID NO: 64 with 0 to 7 amino acid modifications. In some embodiments, the light chain variable region is connected to a light chain constant region, and the light chain constant region comprises an amino acid sequence as shown in SEQ ID NO: 64 with 0 to 6 amino acid modifications. In some embodiments, the light chain variable region is linked to a light chain constant region, which comprises an amino acid sequence as shown in SEQ ID NO: 64 with 0 to 5 amino acid modifications. In some embodiments, the light chain variable region is linked to a light chain constant region, which comprises an amino acid sequence as shown in SEQ ID NO: 64 with 0 to 4 amino acid modifications. In some embodiments, the light chain variable region is linked to a light chain constant region, which comprises an amino acid sequence as shown in SEQ ID NO: 64 with 0 to 3 amino acid modifications. In some embodiments, the light chain variable region is linked to a light chain constant region, which comprises an amino acid sequence as shown in SEQ ID NO: 64 with 0 to 2 amino acid modifications. In some embodiments, the light chain variable region is linked to a light chain constant region, which comprises an amino acid sequence as shown in SEQ ID NO: 64 with 0 to 1 amino acid modifications. In some embodiments, the light chain variable region is linked to a light chain constant region, which comprises an amino acid sequence as shown in SEQ ID NO: 64.

[0042] In some embodiments, the heavy chain constant region comprises an amino acid sequence having at least 90% sequence identity with the amino acid sequence as shown in SEQ ID NO: 61. In some embodiments, the heavy chain constant region comprises an amino acid sequence having at least 95% sequence identity with the amino acid sequence as shown in SEQ ID NO: 61. In some embodiments, the heavy chain constant region comprises an amino acid sequence having at least 97% sequence identity with the amino acid sequence as shown in SEQ ID NO: 61. In some embodiments, the heavy chain constant region comprises an amino acid sequence having at least 98% sequence identity with the amino acid sequence as shown in SEQ ID NO: 61. In some embodiments, the heavy chain constant region comprises an amino acid sequence having at least 99% sequence identity with the amino acid sequence as shown in SEQ ID NO: 61. In some embodiments, the heavy chain constant region comprises an amino acid sequence having 100% sequence identity with the amino acid sequence as shown in SEQ ID NO: 61. In some embodiments, the HCVR is linked to a heavy chain constant region comprising an amino acid sequence as shown in SEQ ID NO: 61, with 0 to 10 amino acid modifications, such as 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid modifications. In some embodiments, the heavy chain constant region comprises an amino acid sequence as shown in SEQ ID NO: 61 with 0 to 9 amino acid modifications. In some embodiments, the heavy chain constant region comprises an amino acid sequence as shown in SEQ ID NO: 61 with 0 to 8 amino acid modifications. In some embodiments, the heavy chain constant region comprises an amino acid sequence as shown in SEQ ID NO: 61 with 0 to 7 amino acid modifications. In some embodiments, the heavy chain constant region comprises an amino acid sequence as shown in SEQ ID NO: 61 with 0 to 6 amino acid modifications. In some embodiments, the heavy chain constant region comprises an amino acid sequence as shown in SEQ ID NO: 61 with 0 to 5 amino acid modifications. In some embodiments, the heavy chain constant region comprises an amino acid sequence as shown in SEQ ID NO: 61 with 0 to 4 amino acid modifications. In some embodiments, the heavy chain constant region comprises an amino acid sequence as shown in SEQ ID NO: 61 with 0 to 3 amino acid modifications. In some embodiments, the heavy chain constant region comprises an amino acid sequence as shown in SEQ ID NO: 61 with 0 to 2 amino acid modifications. In some embodiments, the heavy chain constant region comprises an amino acid sequence as shown in SEQ ID NO: 61 with 0 to 1 amino acid modification. In some embodiments, the heavy chain constant region comprises an amino acid sequence as shown in SEQ ID NO: 61.

[0043] In some embodiments, the HCVR is linked to a heavy chain constant region comprising an amino acid sequence having at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence set forth in SEQ ID NO: 63. In some embodiments, the HCVR is linked to a heavy chain constant region comprising an amino acid sequence having at least 95% sequence identity to the amino acid sequence set forth in SEQ ID NO: 63. In some embodiments, the HCVR is linked to a heavy chain constant region comprising an amino acid sequence having at least 97% sequence identity to the amino acid sequence set forth in SEQ ID NO: 63. In some embodiments, the HCVR is linked to a heavy chain constant region comprising an amino acid sequence having at least 98% sequence identity to the amino acid sequence set forth in SEQ ID NO: 63. In some embodiments, the HCVR is linked to a heavy chain constant region comprising an amino acid sequence having at least 99% sequence identity to the amino acid sequence set forth in SEQ ID NO: 63. In some embodiments, the HCVR is linked to a heavy chain constant region comprising an amino acid sequence having 100% sequence identity with the amino acid sequence as shown in SEQ ID NO: 63. In some embodiments, the HCVR is linked to a heavy chain constant region comprising an amino acid sequence as shown in SEQ ID NO: 63, with 0 to 10 amino acid modifications, such as 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid modifications. In some embodiments, the HCVR is linked to a heavy chain constant region comprising an amino acid sequence as shown in SEQ ID NO: 63 with 0 to 9 amino acid modifications. In some embodiments, the HCVR is linked to a heavy chain constant region comprising an amino acid sequence as shown in SEQ ID NO: 63 with 0 to 8 amino acid modifications. In some embodiments, the HCVR is linked to a heavy chain constant region comprising an amino acid sequence as shown in SEQ ID NO: 63 with 0 to 7 amino acid modifications. In some embodiments, the HCVR is linked to a heavy chain constant region comprising an amino acid sequence as shown in SEQ ID NO: 63 with 0 to 6 amino acid modifications. In some embodiments, the HCVR is linked to a heavy chain constant region comprising an amino acid sequence as shown in SEQ ID NO: 63 with 0 to 5 amino acid modifications. In some embodiments, the HCVR is linked to a heavy chain constant region comprising an amino acid sequence as shown in SEQ ID NO: 63 with 0 to 4 amino acid modifications. In some embodiments, the HCVR is linked to a heavy chain constant region comprising an amino acid sequence as shown in SEQ ID NO: 63 with 0 to 3 amino acid modifications.In some embodiments, the HCVR is linked to a heavy chain constant region comprising an amino acid sequence as shown in SEQ ID NO: 63 with 0 to 2 amino acid modifications. In some embodiments, the HCVR is linked to a heavy chain constant region comprising an amino acid sequence as shown in SEQ ID NO: 63 with 0 to 1 amino acid modifications. In some embodiments, the HCVR is linked to a heavy chain constant region comprising an amino acid sequence as shown in SEQ ID NO: 63.

[0044] In some embodiments, the HCVR is linked to a heavy chain constant region comprising an amino acid sequence having at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence set forth in SEQ ID NO: 75. In some embodiments, the HCVR is linked to a heavy chain constant region comprising an amino acid sequence having at least 95% sequence identity to the amino acid sequence set forth in SEQ ID NO: 75. In some embodiments, the HCVR is linked to a heavy chain constant region comprising an amino acid sequence having at least 97% sequence identity to the amino acid sequence set forth in SEQ ID NO: 75. In some embodiments, the HCVR is linked to a heavy chain constant region comprising an amino acid sequence having at least 98% sequence identity to the amino acid sequence set forth in SEQ ID NO: 75. In some embodiments, the HCVR is linked to a heavy chain constant region comprising an amino acid sequence having at least 99% sequence identity to the amino acid sequence set forth in SEQ ID NO: 75. In some embodiments, the HCVR is linked to a heavy chain constant region comprising an amino acid sequence having 100% sequence identity to the amino acid sequence as shown in SEQ ID NO: 75. In some embodiments, the heavy chain constant region comprises an amino acid sequence as shown in SEQ ID NO: 75, with 0 to 10 amino acid modifications, such as 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid modifications. In some embodiments, the heavy chain constant region comprises an amino acid sequence as shown in SEQ ID NO: 75 with 0 to 9 amino acid modifications. In some embodiments, the heavy chain constant region comprises an amino acid sequence as shown in SEQ ID NO: 75 with 0 to 8 amino acid modifications. In some embodiments, the heavy chain constant region comprises an amino acid sequence as shown in SEQ ID NO: 75 with 0 to 7 amino acid modifications. In some embodiments, the heavy chain constant region comprises an amino acid sequence as shown in SEQ ID NO: 75 with 0 to 6 amino acid modifications. In some embodiments, the heavy chain constant region comprises an amino acid sequence as shown in SEQ ID NO: 75 with 0 to 5 amino acid modifications. In some embodiments, the heavy chain constant region comprises an amino acid sequence as shown in SEQ ID NO: 75 with 0 to 4 amino acid modifications. In some embodiments, the heavy chain constant region comprises an amino acid sequence as shown in SEQ ID NO: 75 with 0 to 3 amino acid modifications. In some embodiments, the heavy chain constant region comprises an amino acid sequence as shown in SEQ ID NO: 75 with 0 to 2 amino acid modifications. In some embodiments, the heavy chain constant region comprises an amino acid sequence as shown in SEQ ID NO: 75 with 0 to 1 amino acid modification.In some embodiments, the heavy chain constant region comprises the amino acid sequence shown in SEQ ID NO:75.

[0045] In some embodiments, the HCVR is linked to a heavy chain constant region comprising an amino acid sequence having at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence set forth in SEQ ID NO: 76. In some embodiments, the HCVR is linked to a heavy chain constant region comprising an amino acid sequence having at least 95% sequence identity to the amino acid sequence set forth in SEQ ID NO: 76. In some embodiments, the HCVR is linked to a heavy chain constant region comprising an amino acid sequence having at least 97% sequence identity to the amino acid sequence set forth in SEQ ID NO: 76. In some embodiments, the HCVR is linked to a heavy chain constant region comprising an amino acid sequence having at least 98% sequence identity to the amino acid sequence set forth in SEQ ID NO: 76. In some embodiments, the HCVR is linked to a heavy chain constant region comprising an amino acid sequence having at least 99% sequence identity to the amino acid sequence set forth in SEQ ID NO: 76. In some embodiments, the HCVR is linked to a heavy chain constant region comprising an amino acid sequence having 100% sequence identity with the amino acid sequence as shown in SEQ ID NO: 76. In some embodiments, the HCVR is linked to a heavy chain constant region comprising an amino acid sequence as shown in SEQ ID NO: 76, with 0 to 10 amino acid modifications, such as 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid modifications. In some embodiments, the HCVR is linked to a heavy chain constant region comprising an amino acid sequence as shown in SEQ ID NO: 76 with 0 to 9 amino acid modifications. In some embodiments, the HCVR is linked to a heavy chain constant region comprising an amino acid sequence as shown in SEQ ID NO: 76 with 0 to 8 amino acid modifications. In some embodiments, the HCVR is linked to a heavy chain constant region comprising an amino acid sequence as shown in SEQ ID NO: 76 with 0 to 7 amino acid modifications. In some embodiments, the HCVR is linked to a heavy chain constant region comprising an amino acid sequence as set forth in SEQ ID NO: 76 with 0 to 6 amino acid modifications. In some embodiments, the HCVR is linked to a heavy chain constant region comprising an amino acid sequence as set forth in SEQ ID NO: 76 with 0 to 5 amino acid modifications. In some embodiments, the HCVR is linked to a heavy chain constant region comprising an amino acid sequence as set forth in SEQ ID NO: 76 with 0 to 4 amino acid modifications. In some embodiments, the HCVR is linked to a heavy chain constant region comprising an amino acid sequence as set forth in SEQ ID NO: 76 with 0 to 3 amino acid modifications.In some embodiments, the HCVR is linked to a heavy chain constant region comprising an amino acid sequence as shown in SEQ ID NO: 76 with 0 to 2 amino acid modifications. In some embodiments, the HCVR is linked to a heavy chain constant region comprising an amino acid sequence as shown in SEQ ID NO: 76 with 0 to 1 amino acid modifications. In some embodiments, the HCVR is linked to a heavy chain constant region comprising an amino acid sequence as shown in SEQ ID NO: 76.

[0046] In some embodiments, the HCVR is linked to a heavy chain constant region, wherein the heavy chain constant region comprises an Fc region comprising one or more of the following amino acids: alanine at position 234 (A), alanine at position 235 (A), aspartic acid at position 236 (D), aspartic acid at position 237 (D), aspartic acid at position 238 (D), alanine at position 265 (A), glutamic acid at position 267 (E), glycine at position 271 (G), arginine at position 330 (R), alanine at position 332 (A), or alanine at position 297 (A) (numbering according to the EU index). In some embodiments, the Fc region comprises an aspartic acid (D) at position 238 (EU index).

[0047] In some embodiments, the HCVR is linked to a heavy chain constant region comprising an amino acid sequence having at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence set forth in SEQ ID NO: 77. In some embodiments, the HCVR is linked to a heavy chain constant region comprising an amino acid sequence having at least 95% sequence identity to the amino acid sequence set forth in SEQ ID NO: 77. In some embodiments, the HCVR is linked to a heavy chain constant region comprising an amino acid sequence having at least 97% sequence identity to the amino acid sequence set forth in SEQ ID NO: 77. In some embodiments, the HCVR is linked to a heavy chain constant region comprising an amino acid sequence having at least 98% sequence identity to the amino acid sequence set forth in SEQ ID NO: 77. In some embodiments, the HCVR is linked to a heavy chain constant region comprising an amino acid sequence having at least 99% sequence identity to the amino acid sequence set forth in SEQ ID NO: 77. In some embodiments, the HCVR is linked to a heavy chain constant region comprising an amino acid sequence having 100% sequence identity with the amino acid sequence as shown in SEQ ID NO: 77. In some embodiments, the HCVR is linked to a heavy chain constant region comprising an amino acid sequence as shown in SEQ ID NO: 77, with 0 to 10 amino acid modifications, such as 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid modifications. In some embodiments, the HCVR is linked to a heavy chain constant region comprising an amino acid sequence as shown in SEQ ID NO: 77 with 0 to 9 amino acid modifications. In some embodiments, the HCVR is linked to a heavy chain constant region comprising an amino acid sequence as shown in SEQ ID NO: 77 with 0 to 8 amino acid modifications. In some embodiments, the HCVR is linked to a heavy chain constant region comprising an amino acid sequence as shown in SEQ ID NO: 77 with 0 to 7 amino acid modifications. In some embodiments, the HCVR is linked to a heavy chain constant region comprising an amino acid sequence as set forth in SEQ ID NO: 77 with 0 to 6 amino acid modifications. In some embodiments, the HCVR is linked to a heavy chain constant region comprising an amino acid sequence as set forth in SEQ ID NO: 77 with 0 to 5 amino acid modifications. In some embodiments, the HCVR is linked to a heavy chain constant region comprising an amino acid sequence as set forth in SEQ ID NO: 77 with 0 to 4 amino acid modifications. In some embodiments, the HCVR is linked to a heavy chain constant region comprising an amino acid sequence as set forth in SEQ ID NO: 77 with 0 to 3 amino acid modifications.In some embodiments, the HCVR is linked to a heavy chain constant region comprising an amino acid sequence as set forth in SEQ ID NO: 77 with 0 to 2 amino acid modifications. In some embodiments, the HCVR is linked to a heavy chain constant region comprising an amino acid sequence as set forth in SEQ ID NO: 77 with 0 to 1 amino acid modifications. In some embodiments, the HCVR is linked to a heavy chain constant region comprising an amino acid sequence as set forth in SEQ ID NO: 77. In some embodiments, X at position 121 of SEQ ID NO: 77 is D. In some embodiments, X at position 121 of SEQ ID NO: 77 is P. In some embodiments, X at position 329 of SEQ ID NO: 77 is G. In some embodiments, X at position 329 of SEQ ID NO: 77 is absent. In some embodiments, X at position 330 of SEQ ID NO: 77 is K. In some embodiments, X at position 330 of SEQ ID NO: 77 is absent.

[0048] In some embodiments, the HCVR is linked to a heavy chain constant region comprising an amino acid sequence having at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence set forth in SEQ ID NO: 78. In some embodiments, the HCVR is linked to a heavy chain constant region comprising an amino acid sequence having at least 95% sequence identity to the amino acid sequence set forth in SEQ ID NO: 78. In some embodiments, the HCVR is linked to a heavy chain constant region comprising an amino acid sequence having at least 97% sequence identity to the amino acid sequence set forth in SEQ ID NO: 78. In some embodiments, the HCVR is linked to a heavy chain constant region comprising an amino acid sequence having at least 98% sequence identity to the amino acid sequence set forth in SEQ ID NO: 78. In some embodiments, the HCVR is linked to a heavy chain constant region comprising an amino acid sequence having at least 99% sequence identity to the amino acid sequence set forth in SEQ ID NO: 78. In some embodiments, the HCVR is linked to a heavy chain constant region comprising an amino acid sequence having 100% sequence identity with the amino acid sequence as shown in SEQ ID NO: 78. In some embodiments, the HCVR is linked to a heavy chain constant region comprising an amino acid sequence as shown in SEQ ID NO: 78, having 0 to 10 amino acid modifications, such as 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid modifications. In some embodiments, the HCVR is linked to a heavy chain constant region comprising an amino acid sequence as shown in SEQ ID NO: 78 with 0 to 9 amino acid modifications. In some embodiments, the HCVR is linked to a heavy chain constant region comprising an amino acid sequence as shown in SEQ ID NO: 78 with 0 to 8 amino acid modifications. In some embodiments, the HCVR is linked to a heavy chain constant region comprising an amino acid sequence as shown in SEQ ID NO: 78 with 0 to 7 amino acid modifications. In some embodiments, the HCVR is linked to a heavy chain constant region comprising an amino acid sequence as set forth in SEQ ID NO: 78 with 0 to 6 amino acid modifications. In some embodiments, the HCVR is linked to a heavy chain constant region comprising an amino acid sequence as set forth in SEQ ID NO: 78 with 0 to 5 amino acid modifications. In some embodiments, the HCVR is linked to a heavy chain constant region comprising an amino acid sequence as set forth in SEQ ID NO: 78 with 0 to 4 amino acid modifications. In some embodiments, the HCVR is linked to a heavy chain constant region comprising an amino acid sequence as set forth in SEQ ID NO: 78 with 0 to 3 amino acid modifications.In some embodiments, the HCVR is linked to a heavy chain constant region comprising an amino acid sequence as set forth in SEQ ID NO: 78 with 0 to 2 amino acid modifications. In some embodiments, the HCVR is linked to a heavy chain constant region comprising an amino acid sequence as set forth in SEQ ID NO: 78 with 0 to 1 amino acid modifications. In some embodiments, the HCVR is linked to a heavy chain constant region comprising an amino acid sequence as set forth in SEQ ID NO: 78. In some embodiments, X at position 108 of SEQ ID NO: 78 is S. In some embodiments, X at position 108 of SEQ ID NO: 78 is P. In some embodiments, X at position 326 of SEQ ID NO: 78 is G. In some embodiments, X at position 326 of SEQ ID NO: 78 is absent. In some embodiments, X at position 327 of SEQ ID NO: 78 is K. In some embodiments, X at position 327 of SEQ ID NO: 78 is absent.

[0049] In some cases, the antibody or antigen-binding fragment thereof binds to a region at or near the C-terminus of the extracellular portion of CD200R.

[0050] In some cases, the antibody or antigen-binding fragment thereof binds to a region up to 50 amino acids, 45 amino acids, 40 amino acids, 35 amino acids, 30 amino acids, 25 amino acids, 20 amino acids, or 15 amino acids from the C-terminus of the extracellular portion of CD200R.

[0051] In some cases, the antibody or antigen-binding fragment thereof binds to a region that is about 50 amino acids, 45 amino acids, 40 amino acids, 35 amino acids, 30 amino acids, 25 amino acids, 20 amino acids, 18 amino acids, 16 amino acids, 15 amino acids, 14 amino acids, 13 amino acids, 12 amino acids, 10 amino acids, 8 amino acids, 6 amino acids, or 5 amino acids from the C-terminus of the extracellular portion of CD200R.

[0052] In some cases, when the antibody or antigen-binding fragment thereof binds to a CD200R molecule on a cell membrane, the antibody or antigen-binding fragment thereof binds to a CD200R molecule at a distance no greater than 100 μm from the cell membrane. area.

[0053] In some cases, when the antibody or antigen-binding fragment thereof binds to a CD200R molecule on a cell membrane, the antibody or antigen-binding fragment thereof binds to a cell membrane approximately 100 μm from the cell membrane. area.

[0054] In some cases, the antibody or antigen-binding fragment thereof binds to a region near the N-terminus of CD200R.

[0055] In some cases, the antibody or antigen-binding fragment thereof binds to a residue of CD200R selected from T213, E230, and S194.

[0056] In some cases, the antibody or antigen-binding fragment thereof binds to a residue of CD200R selected from T213 and E230.

[0057] In some cases, the antibody or antigen-binding fragment thereof does not bind to cynomolgus monkey CD200RLa, or binds to it with a K greater than 2 μM. D Binding to cynomolgus monkey CD200RLa as determined by surface plasmon resonance (SPR) at 37°C.

[0058] In some aspects, disclosed herein is an antibody or antigen-binding fragment thereof that specifically binds to human CD200R or cynomolgus monkey CD200R, wherein the antibody or antigen-binding fragment thereof does not bind to cynomolgus monkey CD200RLa, or binds to cynomolgus monkey CD200RLa with a K of greater than 2 μM. D Binding to cynomolgus monkey CD200RLa as determined by surface plasmon resonance (SPR) at 37°C.

[0059] In some aspects, disclosed herein is an antibody or antigen-binding fragment thereof that specifically binds to CD200R, wherein the antibody or antigen-binding fragment thereof binds to a region at or near the C-terminus of the extracellular portion of CD200R.

[0060] In some cases, the antibody or antigen-binding fragment thereof binds to a residue of CD200R selected from T213 and E230.

[0061] In some cases, the antibody or antigen-binding fragment thereof binds to residues T213 and E230 of CD200R.

[0062] In some cases, the antibody or antigen-binding fragment thereof is an IgG, IgM, IgE, IgA, or IgD molecule, or is derived from one of these.

[0063] In some cases, the antibody or antigen-binding fragment thereof is an IgG1, IgG2, IgG3, or IgG4 molecule, or is derived from one of these.

[0064] In some cases, the antibody is a monoclonal antibody.

[0065] In some cases, the antibody is a human antibody or a humanized antibody.

[0066] In some cases, the antibody is a chimeric antibody.

[0067] In some cases, the antigen-binding fragment thereof is selected from the group consisting of scFv, sc(Fv)2, dsFv, Fab, Fab', (Fab')2, and diabodies.

[0068] In some cases, the antibody or antigen-binding fragment thereof comprises an Fc region.

[0069] In some cases, the Fc region comprises modifications.

[0070] In some cases, the antibody or antigen-binding fragment thereof has increased binding to FcγR2B compared to a parent molecule lacking the Fc region modification.

[0071] In some cases, the antibody or antigen-binding fragment thereof has increased binding to FcγR2B / FcγR2A compared to a parent molecule lacking the Fc region modification.

[0072] In some cases, the Fc region comprises one or more of the following amino acids: alanine at position 234 (A), alanine at position 235 (A), aspartic acid at position 236 (D), aspartic acid at position 237 (D), aspartic acid at position 238 (D), alanine at position 265 (A), glutamic acid at position 267 (E), glycine at position 271 (G), arginine at position 330 (R), alanine at position 332 (A), or alanine at position 297 (A) (all numbering is according to the EU index).

[0073] In some cases, the heavy or light chain also includes a constant region.

[0074] In some cases, the heavy and light chains are connected by a flexible linker to form a single chain antibody.

[0075] In some cases, the antibody or antigen-binding fragment thereof agonizes CD200R expressed on the surface of an immune cell.

[0076] In some cases, when binding to CD200R of an immune cell, the antibody or antigen-binding fragment thereof reduces activation of the immune cell relative to an equivalent immune cell not bound by the antibody or antigen-binding fragment thereof.

[0077] In some cases, when binding to CD200R of an immune cell, the antibody or antigen-binding fragment thereof reduces proliferation of the immune cell relative to an equivalent immune cell not bound by the antibody or antigen-binding fragment thereof.

[0078] In some cases, the reduction in activation or proliferation of immune cells is measured by an assay described in Example 5, Example 16, or Example 17.

[0079] In some cases, the reduction in cell proliferation or activation is measured in vitro or in vivo.

[0080] In some cases, the reduction in cell proliferation or activation is at least about 10%, 15%, 20%, 25%, 30%, 40%, or 50%.

[0081] In some cases, the reduction in cell proliferation or activation is about 10% to 50%, 10% to 40%, 10% to 30%, 10% to 20%, 10% to 15%, 20% to 50%, 20% to 40%, or 20% to 30%.

[0082] In some cases, when binding to CD200R of an immune cell, the antibody or antigen-binding fragment thereof reduces the expression of inflammatory genes in the immune cell relative to an equivalent immune cell not bound by the antibody or antigen-binding fragment thereof.

[0083] In some cases, binding of the antibody or antigen-binding fragment thereof to CD200R expressed on the surface of an immune cell reduces NFκB signaling of the immune cell relative to an equivalent immune cell not bound by the antibody or antigen-binding fragment thereof.

[0084] In some cases, reduction of NFκB signaling of immune cells is measured by the assay described in Example 5.

[0085] In some cases, the reduction in NFKB signaling of an immune cell is at least about 10%, 15%, 20%, 25%, 30%, or 40%.

[0086] In some instances, the reduction in NFKB signaling of an immune cell is about 10% to 40%, 10% to 30%, 10% to 20%, 20% to 40%, or 30% to 40%.

[0087] In some cases, the average maximum inhibition percentage of NFκB signaling in immune cells induced by the antibody or antigen-binding fragment thereof is at least 20%, 30%, 40%, 50% or 60% higher than that of a control antibody, the control antibody comprising: (a) a control heavy chain comprising CDRH1, CDRH2, and CDRH3 comprising the amino acid sequences shown in SEQ ID NOs:55-57, respectively; and (b) a control light chain comprising CDRL1, CDRL2, and CDRL3 comprising the amino acid sequences shown in SEQ ID NOs:58-60, respectively.

[0088] In some cases, the average maximum inhibition percentage of NFκB signaling in immune cells induced by the antibody or antigen-binding fragment thereof is at least 20%, 30%, 40%, 50% or 60% higher than that of a control antibody, the control antibody comprising: a control heavy chain variable region comprising the amino acid sequence shown in SEQ ID NO:53 and a control light chain variable region comprising the amino acid sequence shown in SEQ ID NO:54.

[0089] In some cases, the immune cell is a T cell or a monocyte.

[0090] In some instances, the antibody or antigen-binding fragment thereof inhibits activation of basophils.

[0091] In some instances, the antibody or antigen-binding fragment thereof inhibits activation of basophils induced by FcεRI.

[0092] In some instances, the antibody or antigen-binding fragment thereof inhibits activation of basophils induced by binding of IgE to basophils.

[0093] In some instances, the antibody or antigen-binding fragment thereof inhibits basophil activation by at least 40% or at least 50%.

[0094] In some instances, the antibody or antigen-binding fragment thereof inhibits activation of basophils by about 10% to about 90%, about 20% to about 70%, about 30% to about 60%, or about 40% to about 60%.

[0095] In some cases, the antibody or antigen-binding fragment thereof inhibits the activation of basophils by about 10%, 20%, 30%, 40%, 45%, 50%, 55%, 60%, 70%, 80% or 90%. In some cases, the inhibition of basophil activation is measured in the assay described in Example 10.

[0096] In some cases, the antibody or antigen-binding fragment thereof does not inhibit binding of CD200 to CD200R.

[0097] In some cases, the antibody or antigen-binding fragment thereof has a K of less than 10 nM. D Binding to human CD200R as determined by surface plasmon resonance (SPR) at 37°C.

[0098] In some cases, the antibody or antigen-binding fragment thereof has a K of less than 5 nM. D Binding to human CD200R as determined by surface plasmon resonance (SPR) at 37°C.

[0099] In some cases, the antibody or antigen-binding fragment thereof has a K of less than 2 nM. DBinding to human CD200R as determined by surface plasmon resonance (SPR) at 37°C.

[0100] In some cases, the antibody or antigen-binding fragment thereof has a K of less than 1 nM. D Binding to human CD200R as determined by surface plasmon resonance (SPR) at 37°C.

[0101] In some cases, the antibody or antigen-binding fragment thereof has a K of less than 0.5 nM. D Binding to human CD200R as determined by surface plasmon resonance (SPR) at 37°C.

[0102] In some cases, the antibody or antigen-binding fragment thereof has a K of less than 100 nM. D Binding to cynomolgus CD200R as determined by surface plasmon resonance (SPR) at 37°C.

[0103] In some cases, the antibody or antigen-binding fragment thereof has a K of less than 1 nM. D Binding to cynomolgus CD200R as determined by surface plasmon resonance (SPR) at 37°C.

[0104] In some cases, the antibody or antigen-binding fragment thereof has a K of less than 0.1 nM. D Binding to cynomolgus CD200R as determined by surface plasmon resonance (SPR) at 37°C.

[0105] In some cases, the antibody or antigen-binding fragment thereof has a K of less than 0.01 nM. D Binding to cynomolgus CD200R as determined by surface plasmon resonance (SPR) at 37°C.

[0106] In some cases, when the antibody or antigen-binding fragment thereof binds to CD200R on the surface of an immune cell, the antibody or antigen-binding fragment thereof does not induce significant cytokine release.

[0107] In some cases, the antibody or antigen-binding fragment thereof comprises a domain that binds to an Fc receptor.

[0108] In some cases, Fc receptors are expressed on the surface of immune cells.

[0109] In some cases, the immune cell is an antigen presenting cell.

[0110] In some cases, the antigen presenting cell is a dendritic cell, a macrophage, a monocyte, or a neutrophil.

[0111] In some cases, binding of the antibody or antigen-binding fragment thereof to an Fc receptor expressed on the surface of the immune cell and to CD200R on the surface of a second immune cell results in the cell surface of the immune cell and the cell surface of the second immune cell being altered. or Within.

[0112] In some cases, binding of the antibody or antigen-binding fragment thereof to an Fc receptor expressed on the surface of the immune cell and to CD200R on the surface of a second immune cell results in the cell surface of the immune cell and the cell surface of the second immune cell being altered. or Within.

[0113] In some instances, the Fc receptor is FcγRIIB.

[0114] In some cases, the antibodies or antigen-binding fragments thereof are bispecific or multispecific.

[0115] In some aspects, disclosed herein is an isolated nucleic acid comprising one or more nucleotide sequences encoding a polypeptide capable of forming an antibody or antigen-binding fragment thereof disclosed herein.

[0116] In some aspects, disclosed herein is a vector comprising one or more nucleotide sequences encoding a polypeptide capable of forming an antibody or antigen-binding fragment thereof disclosed herein.

[0117] In some aspects, disclosed herein is a host cell comprising one or more nucleic acid molecules encoding the amino acid sequences of heavy and light chains, which upon expression are capable of forming an antibody or antigen-binding fragment thereof disclosed herein.

[0118] In some aspects, disclosed herein is a method comprising culturing a host cell disclosed herein under conditions whereby an antibody or antigen-binding fragment thereof is produced.

[0119] In some aspects, disclosed herein is a method comprising:

[0120] (a) providing a host cell, the host cell comprising one or more nucleic acid molecules encoding the amino acid sequences of the heavy chain and the light chain, the one or more nucleic acid molecules being capable of forming the antibodies or antigen-binding fragments thereof disclosed herein when expressed;

[0121] (b) culturing a host cell that expresses the encoded amino acid sequence; and

[0122] (c) isolating the antibody or antigen-binding fragment thereof.

[0123] In some aspects, disclosed herein is an immunoconjugate comprising an antibody or antigen-binding fragment thereof disclosed herein conjugated to an agent.

[0124] In some aspects, disclosed herein is a pharmaceutical composition comprising a therapeutically effective amount of an antibody or antigen-binding fragment thereof disclosed herein or an immunoconjugate disclosed herein and at least one pharmaceutically acceptable excipient.

[0125] In some aspects, disclosed herein are antibodies or antigen-binding fragments thereof disclosed herein or immunoconjugates disclosed herein or pharmaceutical compositions disclosed herein for use in therapy.

[0126] In some aspects, disclosed herein is a kit comprising an antibody or antigen-binding fragment thereof disclosed herein, an immunoconjugate disclosed herein, or a pharmaceutical composition disclosed herein in a container.

[0127] In some cases, the kit further comprises informational material containing instructions for use of an antibody or antigen-binding fragment thereof disclosed herein, an immunoconjugate disclosed herein, or a pharmaceutical composition disclosed herein.

[0128] In some aspects, disclosed herein is a method of treating a disease or condition in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of an antibody or antigen-binding fragment thereof disclosed herein or an immunoconjugate disclosed herein, or administering to the subject a pharmaceutical composition disclosed herein.

[0129] In some instances, the disease or disorder comprises a disease or disorder associated with CD200R.

[0130] In some cases, the disease or disorder comprises an autoimmune disease or disorder or an inflammatory disease or disorder.

[0131] In some instances, the disease or condition comprises acute disseminated encephalomyelitis (ADEM), Addison's disease, allergic reaction, alopecia areata, amyotrophic lateral sclerosis, ankylosing spondylitis, antiphospholipid syndrome, asthma, autoimmune hemolytic anemia, autoimmune hepatitis, autoimmune pancreatitis, autoimmune polyendocrine disease syndrome, Behcet's disease, bullous pemphigoid, cerebral malaria, chronic inflammatory demyelinating polyneuritis, celiac disease, Crohn's disease, Cushing's syndrome, dermatitis herpetiformis, dermatomyositis, type 1 diabetes, eosinophilic granulomatosis with polyangiitis, gallbladder disease, graft-versus-host disease, Graves' disease, Guillain-Barré syndrome, Hashimoto's thyroiditis, suppuration hidradenitis, inflammatory bowel disease (IBD), inflammatory fibrosis, irritable bowel syndrome, juvenile arthritis, Kawasaki disease, leukemia, Lyme arthritis, lymphoma, lymphoproliferative disorders, meningoencephalitis, multiple sclerosis, myasthenia gravis, myeloma, neuromyelitis optica, pelvic inflammatory disease, pemphigus, peritonitis, pilonidal disease, polymyositis, primary biliary cholangitis, primary sclerosing cholangitis, psoriasis, psoriatic arthritis, rheumatoid arthritis, sarcoidosis, Sjögren's syndrome, systemic lupus erythematosus, Takayasu's arteritis, temporal arteritis, transplant rejection, transverse myelitis, ulcerative colitis, uveitis, vasculitis, vitiligo, and Vogt-Koyanagi-Harada disease.

[0132] In some cases, the disease or disorder comprises an autoimmune skin disease or disorder.

[0133] In some instances, the autoimmune skin disease or disorder comprises Behcet's disease, dermatitis herpetiformis, dermatomyositis, epidermolysis bullosa, lichen planus, linear IgA disease, cutaneous lupus, morphea / scleroderma, ocular cicatricial pemphigoid, pemphigoid, bullous pemphigoid, pemphigus, psoriasis, scleroderma, or vasculitis.

[0134] In some cases, the subject is a human subject.

[0135] In some aspects, disclosed herein is a method of downregulating an immune response in a subject, the method comprising administering to the subject an antibody or antigen-binding fragment thereof or immunoconjugate disclosed herein, or administering to the subject a pharmaceutical composition disclosed herein.

[0136] In some aspects, disclosed herein is a method of inhibiting an immune cell expressing CD200R, the method comprising contacting the immune cell with an antibody or antigen-binding fragment thereof disclosed herein or an immunoconjugate disclosed herein.

[0137] In some cases, the immune cell comprises a T cell, a B cell, or a macrophage.

[0138] In some cases, the immune cells include antigen-specific T cells.

[0139] In some cases, the subject is a human subject.

[0140] Incorporated by Reference

[0141] All publications, patents, and patent applications mentioned in this specification are herein incorporated by reference to the same extent as if each individual publication, patent, or patent application was specifically and individually indicated to be incorporated by reference. BRIEF DESCRIPTION OF THE DRAWINGS

[0142] The novel features of the present disclosure are particularly set forth in the appended claims. A better understanding of the features and advantages of the present disclosure will be obtained by referring to the following detailed description of exemplary embodiments that illustrate the principles of the present disclosure and the accompanying drawings, in which:

[0143] Figure 1A-1B Surface plasmon resonance (SPR) curves demonstrating the binding of CD200R to CD200 are shown. CD200R was injected into non-competitive clones ( Figure 1A ) and competitive cloning ( Figure 1B ) and was captured by the immobilized anti-CD200R antibody. Figure 1A ), CD200R captured by the non-competitive CD200R antibody can bind to its natural ligand CD200, thus showing an increase in the SPR signal in the graph, while for the competitive clone (in Figure 1B ), CD200R captured by the competitive CD200R antibody cannot bind to its natural ligand CD200, so there is no significant change in the SPR signal in the figure.

[0144] Figure 2 The epitope map of clone 21.3.1 as defined by surface mutagenesis is shown. Surface residues with mutations that reduce antibody binding by >90% relative to the wild-type receptor are indicated by residue numbers (E230 and T213), while surface residues with mutations that have no effect on antibody binding are shaded but not indicated by residue numbers. The epitope was found to be close to the C-terminus of CD200R, very close to the possible location of the cell membrane. As shown in the figure, the orientation of the receptor relative to the cell membrane is predicted by positioning the C-terminus of the extracellular part near the membrane and positioning the N-terminus at the far end of the membrane.

[0145] Figure 3 Shown is an alignment of exemplary humanized VH and VL variants with the murine parental clone 21.3.1 variable domain sequence.

[0146] Figure 4A-4DPredicted immunogenicity based on HLA-DR binding scores is shown for the murine parental variable domain and exemplary humanized variable domains of clone 21.3.1.

[0147] Figure 5A-5D Inhibition of FcεRI-induced basophil activation was demonstrated. Figure 5A is a schematic overview of the experiment. Figure 5B Shown are images of basophils from a single donor 30 minutes after IgE stimulation. Figure 5C-5D A graph showing quantification of basophil activation expressed as CD63+ cell counts ( Figure 5B The light gray objects in the image) divided by the total cell count ( Figure 5B phase objects in the image). Figure 5C Results from a single donor are plotted in Figure 2 . Figure 5D The normalized AUC is summarized in .

[0148] Figure 6A-6C Gene pathways regulated by CD200R signaling are exemplified. Fig. 6A Results of RNA sequencing are shown, which demonstrate the agonistic effects of exemplary CD200R agonistic antibodies according to some embodiments of the present disclosure, wherein 2080 differentially expressed genes were identified when THP-1 cells stimulated in the presence of CD200R agonistic antibodies were compared to isotype controls (899 genes upregulated, 1181 genes downregulated). Figure 6B Shown is a gene set enrichment analysis that revealed that key inflammatory pathways associated with chronic inflammatory conditions were downregulated by CD200R agonism with CD200R agonistic antibodies. Figure 6C CD200R1 was shown to be upregulated in skin biopsies from patients with atopic dermatitis.

[0149] Figure 7 Shown are binding curves of CD200R antibodies or relevant isotype controls to Jurkat T cells expressing human CD200R as assessed by flow cytometry.

[0150] Figure 8 Shown is the output of an enzyme fragment complementation assay reporting DOK2 recruitment to the CD200R cytoplasmic tail in the Jurkat T cell line. DETAILED DESCRIPTION

[0151] In some aspects, disclosed herein are methods, compositions, kits, vectors, polynucleotides, and host cells related to antibodies that recognize the immune cell receptor CD200R. In some embodiments, the antibody or antigen-binding fragment thereof is an agonist antibody. In some embodiments, the agonist antibody specifically binds to CD200R. In some embodiments, the agonist antibody specifically binds to human CD200R.

[0152] In some embodiments, the agonist anti-CD200R antibodies disclosed herein enhance or activate the CD200R signaling pathway. In some embodiments, the anti-CD200R antibodies downregulate immune responses. In some embodiments, the anti-CD200R antibodies downregulate inflammation. In some embodiments, the anti-CD200R antibodies downregulate NF-κB signaling. In some embodiments, the anti-CD200R antibodies reduce immune cell proliferation relative to equivalent immune cells not bound by the anti-CD200R antibodies.

[0153] Without wishing to be bound by a particular theory, the anti-CD200R antibodies disclosed herein enhance the CD200R signaling pathway by enhancing activation of CD200R or signaling pathways induced by activated CD200R, such as interaction of Dok2 with membrane distal tyrosine residues located within the phosphotyrosine binding (PTB) domain recognition motif (NPxY), phosphorylation of tyrosine residues of CD200R, and / or recruitment of SHIP and RasGAP. In some cases, the anti-CD200R antibody binds to CD200R on the surface of an immune cell. In some cases, the anti-CD200R antibody binds to another surface protein expressed on the surface of another immune cell. In some cases, the anti-CD200R antibody can bring the surfaces of two immune cells into close proximity. In some embodiments, such close proximity is In some cases, the close proximity of two immune cells reduces the bulk phosphatase at or near the immune synapse between the two immune cells. In some embodiments, the bulk phosphatase contributes to the dephosphorylation of CD200R. In some embodiments, the reduced bulk phosphatase leads to more CD200R phosphorylation, which in turn enhances the CD200R signaling pathway. In some embodiments, the immune cell is a T cell. In some cases, the immune cell is a monocyte.

[0154] In some embodiments, the anti-CD200R antibody recognizes the extracellular region of human CD200R. In some embodiments, the antibody recognizes the extracellular region of cynomolgus CD200R. In some embodiments, the anti-CD200R antibody does not compete with the natural ligand of CD200R. In some cases, the antibody binds to a region near the C-terminus of CD200R or the C-terminus of the extracellular portion of CD200R. In some cases, the anti-CD200R antibody binds to a region close to a possible position of the cell membrane. In some cases, the antibody binds to a region close to the N-terminus of domain 2. When expressed on the surface of the cell membrane, CD200R may have an extracellular portion, a transmembrane portion, and an intracellular portion. When expressed on the surface of the cell membrane, CD200R may have two IgSF domains in its extracellular portion, domain 1 and domain 2, for example, as described in Wright et al. J Immunol 2003; 171: 3034-3046, which is incorporated herein by reference in its entirety. Domain 1 is the N-terminal domain in the extracellular portion of CD200R and domain 2 is the C-terminal domain in the extracellular portion of CD200R. CD200R domain 2 is the domain that is closer to the membrane.

[0155] In other cases, the anti-CD200R antibody binds to an area further from the cell membrane. In some embodiments, the anti-CD200R binds to the T213 residue of CD200R. In some embodiments, the anti-CD200R binds to the E230 residue of CD200R. In some embodiments, the anti-CD200R binds to the T213 residue and the E230 residue of CD200R. In some embodiments, the anti-CD200R binds to the S194 residue of CD200R.

[0156] In some embodiments, the disclosed CD200R agonistic antibodies are more effective than currently existing antibodies (e.g., I-4P described in Example 5) in promoting CD200R inhibitory signaling to immune cells and / or the immune system, downregulating immune cell responses. In some cases, the anti-CD200R antibodies disclosed herein are more effective than currently existing antibodies (e.g., I-4P) in enhancing CD200R inhibition of the NF-κB pathway. The anti-CD200R antibodies disclosed herein are particularly useful for treating immune-mediated and / or CD200R-related disorders, or diseases resulting from abnormal immune pathology or having a cancerous origin.

[0157] In some embodiments, the antibody is a human antibody. In some embodiments, the CD200R antibody disclosed herein is a humanized antibody. In some embodiments, the CD200R agonist antibody is a monoclonal antibody. In some embodiments, the CD200R antibody is a chimeric antibody. In some embodiments, the CD200R antibody is produced in mice. In some embodiments, the CD200R antibody comprises one or more modifications in its Fc region. In some embodiments, the CD200R antibody comprises one or more modifications in its heavy chain. In some embodiments, the CD200R antibody comprises one or more modifications in its light chain.

[0158] In some embodiments, the CD200R antibody is an IgG molecule or is derived from an IgG molecule. In some embodiments, the CD200R antibody is an IgM molecule or is derived from an IgM molecule. In some embodiments, the CD200R antibody is an IgE molecule or is derived from an IgE molecule. In some embodiments, the CD200R antibody is an IgA molecule or is derived from an IgA molecule. In some embodiments, the CD200R antibody is an IgD molecule or is derived from an IgD molecule.

[0159] In some aspects, disclosed herein are compositions, systems, pharmaceutical compositions, therapeutic methods, kits, and manufacturing methods involving CD200R antibodies.

[0160] It should be understood that one, some or all of the properties of the various embodiments described herein may be applied to any aspect, unless the content clearly specifies otherwise. In addition, the various embodiments may be combined to form other embodiments of the present disclosure. These and other aspects of the present disclosure will be apparent to those skilled in the art. These and other embodiments of the present disclosure are further described by the specific embodiments below.

[0161] definition

[0162] As used herein, the terms "agonist", "agonistic", "agonism" and other grammatical equivalents refer to or relate to an agent that is capable of binding to a receptor or any other protein target and activating or enhancing the activity of a receptor or protein target or helping to initiate activation of a receptor or protein target. In some cases, an agonist can promote the receptor or other protein target to which it binds to induce a biological response, such as signal transduction or other changes in cell activity. As used herein, a CD200R agonistic antibody (or antibody fragment) refers to an antibody (or antibody fragment) that binds to CD200R expressed on the surface of an immune cell and enhances its inhibitory signal to immune cells (including but not limited to T cells, macrophages and / or B lymphocytes).

[0163] Throughout this disclosure, wherever aspects are described herein with the language “comprising,” other similar aspects are provided that are described as “consisting of” and / or “consisting essentially of. All definitions described herein, whether specifically mentioned or not, should be understood to refer to definitions used throughout the specification and the appended claims.

[0164] Throughout the specification and the appended claims, the singular forms "a", "an", and "the" include plural referents unless the context clearly dictates otherwise. For example, the term "a cell" includes a plurality of cells, including mixtures thereof.

[0165] In the present disclosure, one, some or all properties of the various embodiments described herein may be applied to any aspect, unless the content clearly specifies otherwise. In addition, the various embodiments may be combined to form other embodiments of the present disclosure. These aspects and other aspects of the present disclosure will be apparent to those skilled in the art. These embodiments and other embodiments of the present disclosure are further described by the specific embodiments herein.

[0166] Throughout the specification and the appended claims, unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which the present disclosure relates. For example, "The Concise Dictionary of Biomedicine and Molecular Biology", Juo, Pei-Show, 2nd edition, 2002, CRC Press; "The Dictionary of Cell and Molecular Biology", 3rd edition, 1999, Academic Press; and "Oxford Dictionary of Biochemistry and Molecular Biology", revised edition, 2000, Oxford University Press provide a general dictionary of many of the terms used in the present disclosure for one of ordinary skill in the art.

[0167] Amino acids may be referred to herein by either their commonly known three letter symbols or by the single letter symbols recommended by the IUPAC-IUB Biochemical Nomenclature Commission. Likewise, nucleotides may be referred to by their commonly accepted single letter codes.

[0168] Unless otherwise indicated, the numbering of amino acids in the variable domains, CDRs, and framework regions (FRs) of antibodies follows the Kabat definition as described in Kabat et al., "Sequences of Proteins of Immunological Interest", 5th Edition, Public Health Service, National Institutes of Health, Bethesda, MD. (1991).

[0169] The term "about" or "approximately" means within an acceptable error range for a particular value as determined by one of ordinary skill in the art, which will depend in part on how the value is measured or determined, i.e., the limitations of the measurement system. For example, according to the practice in the art, "about" may mean within 1 or more than 1 standard deviation. Alternatively, "about" may mean a range of up to 20%, up to 10%, up to 5%, or up to 1% of a given value. Alternatively, particularly with respect to biological systems or processes, the term may mean within an order of magnitude of a value, preferably within 5 times and more preferably within 2 times. When describing a particular value in the present application and claims, unless otherwise stated, it should be assumed that the term "about" means within an acceptable error range for a particular value.

[0170] The terms "polypeptide," "oligopeptide," "peptide," and "protein" are used interchangeably herein to refer to polymers of amino acids of any length. The polymer may be linear or branched, it may contain modified amino acids, and it may be interrupted by non-amino acids. The term also encompasses naturally modified amino acid polymers or amino acid polymers modified by intervention; for example, disulfide bond formation, glycosylation, lipidation, acetylation, phosphorylation, or any other manipulation or modification, such as conjugation with a tag component. Also included in the definition are, for example, polypeptides containing one or more amino acid analogs (including, for example, non-natural amino acids, etc.), as well as other modifications known in the art. It should be understood that because the polypeptides described herein are antibody-based, the polypeptides may exist as single chains or associated chains.

[0171] The term "amino acid" refers to natural amino acids, unnatural amino acids, and synthetic amino acids, including but not limited to D optical isomers or L optical isomers, and amino acid analogs and peptidomimetics. Standard single-letter codes or three-letter codes are used to represent amino acids.

[0172] When applied to proteins, a "variant" is a protein having sequence homology with a native biologically active protein that retains at least a portion of the therapeutic activity and / or biological activity of the biologically active protein. For example, a variant protein may have at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99% amino acid sequence identity, or any range between at least 70% and 99%, compared to a reference biologically active protein. As used herein, the term "biologically active protein portion" includes proteins that have been intentionally modified, such as, for example, by site-directed mutagenesis, synthesis of an encoding gene, insertion, or accidentally by mutation.

[0173] In the context of polypeptides, a "linear sequence" or "sequence" is the order of amino acids in a polypeptide in the amino to carboxyl terminal direction, wherein residues adjacent to each other in the sequence are contiguous in the primary structure of the polypeptide. A "partial sequence" is the linear sequence of a portion of a polypeptide, known to contain additional residues in one or both directions.

[0174] "Polynucleotide" or "nucleic acid" used interchangeably herein refers to a polymer of nucleotides of any length, and includes DNA and RNA. The nucleotides can be deoxyribonucleotides, ribonucleotides, modified nucleotides or bases, and / or their analogs, or any substrate that can be incorporated into a polymer by DNA or RNA polymerase. The polynucleotide may contain modified nucleotides, such as methylated nucleotides and their analogs. If present, the nucleotide structure may be modified before or after polymer assembly. The nucleotide sequence may be interrupted by non-nucleotide components. The polynucleotide may be further modified after polymerization, such as by conjugation with a tag component. Other types of modifications include, for example, "caps", substitution of one or more naturally occurring nucleotides with analogs, internucleotide modifications (such as, for example, those with uncharged bonds (e.g., methylphosphonates, phosphotriesters, phosphoramidates, carbamates, etc.) and with charged bonds (e.g., phosphorothioates, phosphorodithioates, etc.); those containing side groups, such as, for example, proteins (e.g., nucleases, toxins, antibodies, signal peptides, ply-L-lysine, etc.); those with intercalators (e.g., acridine, psoralen, etc.); those containing chelators (e.g., metals, radioactive metals, boron, oxidative metals, etc.); those containing alkylating agents; those with modified bonds (e.g., alpha anomeric nucleic acids, etc.), as well as unmodified forms of polynucleotides. In addition, any hydroxyl groups typically present in the sugar may be substituted, for example, with phosphonate groups, phosphate groups, protected by standard protecting groups, or activated to enable additional attachment to additional nucleotides, or may be conjugated to a solid support. The 5' terminal OH and 3' terminal OH can be phosphorylated or partially replaced by amines or organic end-capping groups of 1 to 20 carbon atoms. Other hydroxyls can also be derived as standard protecting groups. Polynucleotides can also contain similar forms of ribose or deoxyribose that are well known in the art, including, for example, 2'-O-methyl-, 2'-O-allyl, 2'-fluoro- or 2'-azido-ribose, carbocyclic sugar analogs, α-anomeric sugars, epimeric sugars (such as arabinose, xylose or lyxose), pyranose, furanose, sedoheptulose, acyclic analogs and abasic nucleoside analogs (such as methyl nucleosides). One or more phosphodiester bonds can be replaced by alternative linking groups. These alternative linking groups include, but are not limited to, phosphates that are replaced by P(O)S ("thio"), P(S)S ("dithio"), (O)NR 2 ("amidation"), P(O)R, P(O)OR', CO or CH 2("methylal") alternative embodiments, wherein each R or R' is independently H or a substituted or unsubstituted alkyl (1 to 20 carbon atoms), aryl, alkenyl, cycloalkyl, cycloalkenyl or aralkyl group optionally containing an ether (-O-) bond. Not all bonds in a polynucleotide need to be the same. The foregoing description applies to all polynucleotides referred to herein, including RNA and DNA.

[0175] The "variable region" of an antibody refers to the variable region of the antibody light chain or the variable region of the antibody heavy chain, alone or in combination. The variable regions of the heavy and light chains are each composed of four framework regions (FRs) connected by three complementary determining regions (CDRs) (also called hypervariable regions). The CDRs in each chain are held together in close proximity by the FRs and, together with the CDRs from the other chain, contribute to the formation of the antigen binding site of the antibody. There are at least two techniques for determining CDRs: (1) methods based on cross-species sequence variability (i.e., Kabat et al., Sequences of Proteins of Immunological Interest (5th ed., 1991, National Institutes of Health, Bethesda, Maryland)); and (2) methods based on crystallographic studies of antigen-antibody complexes (Al-lazikani et al. (1997) J. Molec. Biol. 273:927-948). As used herein, CDRs may refer to CDRs defined by either method or by a combination of both methods.

[0176] The "constant region" of an antibody refers to the constant region of the antibody light chain or the constant region of the antibody heavy chain, alone or in combination.

[0177] "Host cell" includes a single cell or cell culture that can be or has been a recipient of a vector comprising an exogenous polynucleotide. Host cells include progeny of a single host cell, and the progeny may not necessarily be completely identical (in morphology or genomic DNA complement) to the original parent cell due to natural, accidental or deliberate mutation. Host cells include cells transfected in vivo with a polynucleotide of the present disclosure.

[0178] The term "Fc region" is used to define the C-terminal region of an immunoglobulin heavy chain. An "Fc region" may be a native sequence Fc region or a variant Fc region. Although the boundaries of the Fc region of an immunoglobulin heavy chain may be different, the human IgG heavy chain Fc region is generally defined as extending from the amino acid residue at position Cys226 or from Pro230 to its carboxyl terminus. The numbering of the residues in the Fc region is the numbering of the EU index as in Kabat. (Kabat et al., Sequences of Proteins of Immunological Interest, 5th Edition Public Health Service, National Institutes of Health, Bethesda, Md., 1991.) The Fc region of an immunoglobulin generally comprises two constant domains, CH2 and CH3.

[0179] A "functional Fc region" has at least one "effector function" of a native sequence Fc region. Exemplary "effector functions" include C1q binding; complement dependent cytotoxicity (CDC); Fc receptor binding; antibody-dependent cell-mediated cytotoxicity (ADCC); phagocytosis; downregulation of cell surface receptors (e.g., B cell receptor; BCR), etc. Such effector functions generally require an Fc region in combination with a binding domain (e.g., an antibody variable domain), and can be assessed using various assays known in the art for evaluating such antibody effector functions.

[0180] A "native sequence Fc region" comprises an amino acid sequence identical to the amino acid sequence of a naturally occurring Fc region. A "variant Fc region" comprises an amino acid sequence that differs from the amino acid sequence of a native sequence Fc region due to at least one amino acid modification but retains at least one effector function of the native sequence Fc region. Preferably, the variant Fc region has at least one amino acid substitution compared to the native sequence Fc region or the Fc region of a parent polypeptide, for example, about 1 to about 10 amino acid substitutions in the native sequence Fc region or the Fc region of a parent polypeptide, and preferably about 1 to about 5 amino acid substitutions. The variant Fc region herein will preferably have at least about 80% sequence identity with the native sequence Fc region and / or the Fc region of a parent polypeptide, and most preferably at least about 90% sequence identity therewith, more preferably at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99% sequence identity therewith, and sequence identity therewith between the ranges.

[0181] An "individual" or "subject" is a mammal, more preferably a human. Mammals also include, but are not limited to, farm animals, sports animals, pets, primates, horses, dogs, cats, mice, and rats.

[0182] As used herein, "vector" means a construct capable of delivering and preferably expressing one or more genes or sequences of interest in a host cell. Examples of vectors include, but are not limited to, viral vectors, naked DNA or RNA expression vectors, plasmids, cosmids or phage vectors, DNA or RNA expression vectors associated with cationic condensing agents, DNA or RNA expression vectors encapsulated in liposomes, and certain eukaryotic cells such as production cells.

[0183] The term "effective amount" or "therapeutically effective amount" refers to the amount of the medicament sufficient to achieve a beneficial or desired result. The therapeutically effective amount may vary according to one or more of the following: the subject and the condition being treated, the subject's weight and age, the severity of the condition, the mode of administration, etc., which can be easily determined by a person of ordinary skill in the art. The term "effective amount" is also applicable to the dosage for providing an image for detection by an appropriate imaging method. The specific dosage may vary according to one or more of the following: the specific medicament selected, the dosing regimen to be followed, whether the medicament is administered in combination with other compounds, the time schedule for administration, the tissue to be imaged, and the physical delivery system carrying the medicament. The active agent of the effective amount can be administered in a single dose or multiple doses. The therapeutically effective amount of the antibody ranges from about 0.001 mg / kg body weight to about 25 mg / kg body weight, preferably from about 0.01 mg / kg body weight to about 25 mg / kg body weight, from about 0.1 mg / kg body weight to about 20 mg / kg body weight, or from about 1 mg / kg to about 10 mg / kg. As determined by one of ordinary skill in the art, the dosage may be adjusted as necessary to suit the observed therapeutic effect and / or to most effectively cure, prevent, control symptoms, etc. The treating physician or person skilled in the art selects the appropriate dosage based on the clinical indication. The component may be described herein as having at least an effective amount, or at least an amount effective to produce a desired result, such as a result associated with a particular goal or purpose, such as any result described herein. The desired therapeutic results herein may include, but are not limited to, treating, alleviating or curing a condition, cancer, immune-related disease, CD200R-related condition, and / or any symptom from an immune-related pathology, etc. as described in this specification and / or the appended claims.

[0184] As used herein, "pharmaceutically acceptable carrier" or "pharmaceutically acceptable excipient" includes any material that, when combined with an active ingredient, allows the ingredient to remain biologically active and does not react with the subject's immune system. Examples include, but are not limited to, any of the standard pharmaceutical carriers, such as phosphate-buffered saline solutions, water, emulsions such as oil / water emulsions, and various types of wetting agents. Preferred diluents for aerosol or parenteral administration are phosphate-buffered saline or normal saline (0.9%). Compositions containing such carriers are formulated by well-known conventional methods (see, e.g., Remington's Pharmaceutical Sciences, 18th edition, A. Gennaro, ed., Mack Publishing Co., Easton, PA, 1990; and Remington, The Science and Practice of Pharmacy 20th edition, Mack Publishing, 2000).

[0185] Throughout the specification and the appended claims, unless otherwise indicated, the methods and systems disclosed herein as described herein can adopt the conventional techniques and descriptions of molecular biology (including recombinant technology), cell biology, biochemistry, microarray and sequencing technology, and these techniques and descriptions are within the skill range of those skilled in the art. Such conventional techniques include polymer array synthesis, hybridization and connection of oligonucleotides, sequencing of oligonucleotides and hybridization detection using labels. The specific embodiments of suitable technology can be referred to the embodiments of this paper. However, of course, equivalent conventional procedures can also be used.Such routine techniques and descriptions can be found in standard laboratory manuals, such as Green et al., eds., Genome Analysis: A Laboratory Manual Series (Volumes I-IV) (1999); Weiner et al., eds., Genetic Variation: A Laboratory Manual (2007); Dieffenbach, Dveksler, eds., PCR Primer: A Laboratory Manual (2003); Bowtell and Sambrook, DNA Microarrays: A Molecular Cloning Manual (2003); Mount, Bioinformatics: Sequence and Genome Analysis (2004); Sambrook and Russell, Condensed Protocols from Molecular Cloning: A Laboratory Manual (2006); and Sambrook and Green, Molecular Cloning: A Laboratory Manual, 4th edition (2012) (all from Cold Spring Harbor Laboratory Press); Stryer, L., Biochemistry (4th edition) WH Freeman, New York (1995); Gait, "Oligonucleotide Synthesis: A Practical Approach" IRL Press, London (1984); Nelson and Cox, Lehninger, Principles of Biochemistry, 6th Edition, WH Freeman Pub., New York (2012); RI Freshney, Culture of Animal Cells: A Manual of Basic Technique and Specialized Applications, 6th Edition, Wiley-Blackwell (2010); and Berg et al., Biochemistry, 5th Edition, WH Freeman Pub., New York (2002), all of which are incorporated herein by reference in their entirety for all purposes. Before describing the compositions, research tools and systems and methods of the present invention, it should be understood that this disclosure is not limited to the particular systems and methods, compositions, objects and uses described, as they may, of course, vary.It is also to be understood that the terminology used herein is for the purpose of describing particular aspects only, and is not intended to limit the scope of the present disclosure, which will be limited only by the appended claims.

[0186] As used herein, the term "anti-CD200R antibody" or molecule refers to both antibodies and binding fragments thereof that are capable of binding to CD200R.

[0187] In the present disclosure, "antibody" refers to an immunoglobulin molecule that can specifically bind to a target (such as a carbohydrate, polynucleotide, lipid, polypeptide, etc.) through at least one antigen recognition site located in the variable region of the immunoglobulin molecule. As used herein, the term includes immunoglobulin molecules that specifically bind to an antigen and contain an FcR binding site, which may or may not be functional. As used in the present disclosure, the term covers not only complete polyclonal antibodies or monoclonal antibodies, but also fragments thereof (such as Fab, Fab', F(ab')2, diabodies), Fv fragments, and single-chain (ScFv) mutants, which contain antigen recognition sites or antigen binding sites and have the ability to bind to antigens. Antigen-binding antibodies or immunoglobulin fragments are well known in the art; such fragments may have functional or non-functional Fc receptor binding sites. Furthermore, as used herein, the term is not limited to intact polyclonal or monoclonal antibodies, multispecific antibodies (such as bispecific or multispecific antibodies produced from at least two intact antibodies), chimeric antibodies, humanized antibodies, single chain antibodies, chimeric antibodies, synthetic antibodies, recombinant antibodies, hybrid antibodies, mutated antibodies, grafted antibodies, human antibodies and any other modified immunoglobulin molecules that contain an antigen binding site, so long as these antibodies exhibit the desired biological activity.

[0188] There are five major classes of immunoglobulins: IgA, IgD, IgE, IgG and IgM, and several of these immunoglobulins can be further divided into subclasses (isotypes), such as IgG1, IgG2, IgG3, IgG4, IgA1 and IgA2. The heavy chain constant domains corresponding to the immunoglobulins of different classes are referred to as α, δ, ε, γ and μ, respectively. The subunit structure and three-dimensional configuration of the immunoglobulins of different classes are well known. Unless otherwise specified by the contextual limitations, the antibodies of the present disclosure may be from one of these antibody classes or subclasses. The heavy chain constant domains corresponding to the antibodies of different classes are generally represented by the corresponding lowercase Greek letters α, δ, ε, γ and μ, respectively. The light chain of the antibody from any vertebrate species can be designated as one of two distinctly different types (referred to as kappa (κ) and lambda (λ)) based on the amino acid sequence of its constant domain.

[0189] Throughout the specification and the appended claims, "Fc receptor" and "FcR" describe a receptor that binds to the Fc region of an antibody. FcRs are reviewed in the following literature: Ravetch and Kinet, 1991, Ann. Rev. Immunol., 9:457-92; Capel et al., 1994, Immunomethods, 4:25-34; and de Haas et al., 1995, J. Lab. Clin. Med., 126:330-41. "FcR" also includes the neonatal receptor FcRn, which is responsible for the transfer of maternal IgG to the fetus (Guyer et al., 1976, J. Immunol., 117:587; and Kim et al., 1994, J. Immunol., 24:249).

[0190] When used in this article, "monoclonal antibody" refers to an antibody obtained from a substantially homogeneous antibody population. Generally, the individual antibodies constituting the population are identical, except for possible naturally occurring mutations that may be present in trace amounts. Monoclonal antibodies are highly specific, directed against a single antigenic site. In addition, in contrast to polyclonal antibody preparations that typically include different antibodies directed against different determinants (epitopes), each monoclonal antibody is directed against a single determinant on an antigen. The modifier "monoclonal" indicates the characteristics of an antibody obtained from a substantially homogeneous antibody population, and should not be interpreted as requiring antibodies to be produced by any particular method. For example, the monoclonal antibodies used according to the present disclosure can be prepared by the hybridoma method first described by Kohler and Milstein, 1975, Nature 256:495, or can be prepared by recombinant DNA methods (such as described in U.S. Patent No. 4,816,567). Monoclonal antibodies can also be isolated from phage libraries produced using, for example, McCafferty et al., 1990, Nature, 348:552-554.

[0191] When used herein, "human antibody" means an antibody having an amino acid sequence corresponding to the amino acid sequence of an antibody produced by a human, and / or has been prepared using any technique known in the art or disclosed herein for preparing human antibodies. This definition of human antibodies includes antibodies comprising at least one human heavy chain polypeptide or at least one human light chain polypeptide. One such example is an antibody comprising a murine light chain and a human heavy chain polypeptide. Human antibodies can be produced using various techniques known in the art. In some cases, human antibodies are selected from a phage library, wherein the phage library expresses human antibodies (Vaughan et al., 1996, Nature Biotechnology, 14: 309-314; Sheets et al., 1998, PNAS, (USA) 95: 6157-6162; Hoogenboom and Winter, 1991, J. Mol. Biol., 227: 381; Marks et al., 1991, J. Mol. Biol., 222: 581). Human antibodies can also be prepared by introducing human immunoglobulin loci into transgenic animals (e.g., mice in which endogenous immunoglobulin genes have been partially or completely inactivated). This method is described in U.S. Patents Nos. 5,545,807, 5,545,806, 5,569,825, 5,625,126, 5,633,425, and 5,661,016. Alternatively, human antibodies can be prepared by immortalizing human B lymphocytes that produce antibodies against target antigens (such B lymphocytes can be recovered from individuals or can have been immunized in vitro). See, e.g., Cole et al., Monoclonal Antibodies and Cancer Therapy, Alan R. Liss, p. 77 (1985); Boerner et al., 1991, J. Immunol., 147 (1): 86-95; and U.S. Patent No. 5,750,373.

[0192] As used herein, "humanized" antibodies refer to forms of non-human (e.g., murine) antibodies that are specific chimeric immunoglobulins, immunoglobulin chains, or fragments thereof (such as Fv, Fab, Fab', F(ab')2, or other antigen-binding subsequences of antibodies) containing minimal sequences derived from non-human immunoglobulins. In most cases, humanized antibodies are human immunoglobulins (receptor antibodies) in which residues from the complementary determining regions (CDRs) of the receptor are replaced with residues from non-human species (donor antibodies) such as mice, rats, or rabbits with the desired specificity, affinity, and biological activity of the CDRs. In some cases, the Fv framework region (FR) residues of human immunoglobulins are replaced with corresponding non-human residues. In addition, humanized antibodies may include residues that are neither present in the receptor antibody nor in the imported CDR or framework sequences, but the inclusion of the residues is to further improve and optimize antibody performance. In general, humanized antibodies will comprise substantially all of at least one, usually two variable domains, wherein all or substantially all of the CDR regions correspond to the CDR regions of non-human immunoglobulins, and all or substantially all of the framework (FR) regions are framework regions of human immunoglobulin consensus sequences. Humanized antibodies will also optimally comprise at least a portion of an immunoglobulin constant region or domain (Fc) (typically a constant region of a human immunoglobulin). The antibody may have an Fc region modified as described in WO 99 / 58572. Other forms of humanized antibodies have one or more (one, two, three, four, five, six) CDRs that are changed relative to the original antibody, which are also referred to as "derived from" one or more CDRs from the original antibody.

[0193] As used herein, the term "chimeric antibody" may refer to an antibody in which the variable region sequence is derived from one species and the constant region sequence is derived from another species, such as an antibody in which the variable region sequence is derived from a mouse antibody and the constant region sequence is derived from a human antibody. In some embodiments, the antibodies provided herein are monoclonal antibodies.

[0194] As used herein, "antibody-dependent cell-mediated cytotoxicity" and "ADCC" refer to cell-mediated reactions in which nonspecific cytotoxic cells (e.g., natural killer (NK) cells, neutrophils, and macrophages) expressing Fc receptors (FcRs) recognize the antibody bound on target cells and subsequently cause the lysis of target cells. The ADCC activity of the molecule of interest can be assessed using an in vitro ADCC assay, such as described in U.S. Patent Nos. 5,500,362 or 5,821,337. Effector cells that can be used for such assays include peripheral blood mononuclear cells (PBMC) and NK cells. Alternatively or in addition, the ADCC activity of the molecule of interest can be assessed in vivo (e.g., in an animal model (such as Clynes et al., 1998, PNAS (USA), 95: Animal models disclosed in 652-656)).

[0195] "Complement dependent cytotoxicity" and "CDC" refer to the lysis of a target in the presence of complement. The complement activation pathway is initiated by the binding of the first component of the complement system (C1q) to a molecule (e.g., an antibody) complexed with a cognate antigen. To assess complement activation, a CDC assay may be performed, e.g., as described in Gazzano-Santoro et al., J. Immunol. Methods, 202: 163 (1996).

[0196] An antibody that "specifically binds" to an epitope is a term well known in the art, and methods for determining such specific binding are also well known in the art. If a molecule reacts or associates with a specific cell, protein, or substance more frequently, more rapidly, for a longer duration, and / or with greater affinity than it does with alternative cells, proteins, or substances, then the molecule is said to exhibit "specific binding." If an antibody binds to a target with greater affinity, avidity, more readily, and / or for a longer duration than it binds to other substances, then the antibody "specifically binds" or "preferentially binds" to the target. For example, an antibody that specifically or preferentially binds to CD200R is an antibody that binds to the epitope with greater affinity, avidity, more readily, and / or for a longer duration than it binds to other epitopes. As a further example, an antibody (or other moiety) that specifically or preferentially binds to a first target may or may not specifically or preferentially bind to a second target. Therefore, "specific binding" or "preferential binding" does not necessarily require (although it may include) exclusive binding. Typically, but not necessarily, reference to binding means preferential binding.

[0197] When applied to proteins, a "fragment" is a truncated form of a native biologically active protein that may or may not retain at least a portion of the therapeutic activity and / or biological activity. In this article, the terms "antibody fragment molecules of the present disclosure," "antibody fragments," and "antigen-binding fragments thereof" are used interchangeably herein.

[0198] Sequence identity

[0199] Sequence identity with respect to anti-CD200R antibodies or any other amino acid sequence identified herein is defined as the percentage of amino acid residues in the query sequence that are identical to the amino acid residues of a second reference polypeptide sequence or a portion thereof, after aligning the sequences and introducing gaps (if necessary) to obtain the maximum percentage of sequence identity and not considering any conservative substitutions as part of the sequence identity. Alignment for determining percentage of amino acid sequence identity can be achieved in various ways within the skill in the art, for example, using publicly available computer software such as BLAST, BLAST-2, ALIGN or Megalign (DNASTAR) software. One skilled in the art can determine appropriate parameters for measuring alignment, including any algorithm necessary to achieve maximum alignment over the full length of the sequences being compared. Percent identity can be measured over the length of the entire defined polypeptide sequence, or can be measured over a shorter length, for example, over the length of a fragment taken from a larger defined polypeptide sequence, for example, a fragment of at least 15, at least 20, at least 30, at least 40, at least 50, at least 70 or at least 150 consecutive residues. Such length is only exemplary, and it should be understood that any fragment length supported by the sequence shown in this article, table, accompanying drawing or sequence table can be used to describe the length of measurable identity percentage.In some embodiments, percentage identity is determined relative to the total length of the reference sequence (such as sequence provided herein).For example, the sequence comparison between two amino acid sequences of the present disclosure (or its shorter length) can be carried out by the computer program Blastp (protein-protein BLAST) provided online by the National Center for Biotechnology Information (NCBI).The amino acid sequence identity percentage of a given amino acid sequence A and a given amino acid sequence B (alternatively, it can be expressed as a given amino acid sequence A with a certain % amino acid sequence identity with a given amino acid sequence B) is calculated by the following formula:

[0200]

[0201] wherein X is the number of amino acid residues scored as identical matches by the sequence alignment program BLAST in that program's alignment of A and B, and wherein Y is the total number of amino acid residues in the shorter of A or B.

[0202] Two polynucleotide sequences or polypeptide sequences are considered "identical" if the sequence of nucleotides or amino acids in the two sequences is the same when aligned for maximum correspondence as described below. Comparisons between two sequences are typically performed by comparing the sequences over a comparison window to identify and compare local regions of sequence similarity.

[0203] CD200 and CD200R

[0204] In some aspects, provided herein are compositions and methods involving antibodies or antibody fragments that bind and agonize CD200R, a receptor that can be present on the surface of immune cells, including T cells, natural killer cells, B cells, monocytes, myeloid cells, macrophages, microglia, and dendritic cells. CD200:CD200R plays a key role in limiting immune cell proliferation, immune responses, and inflammation.

[0205] Without wishing to be bound by a particular theory, activation of the CD200R signaling pathway results in inhibition of immune cell activation and proliferation. Antibodies that enhance CD200R signaling have the potential to downregulate inflammation and immune responses in infections, arthritis, cancer, autoimmune diseases, transplant rejection, or other diseases or conditions associated with CD200R. CD200 is a member of the immunoglobulin superfamily (IgSF) and a transmembrane type 1a glycoprotein, and can be highly expressed in a variety of cell types, such as dendritic cells, macrophages, B lymphocytes, neuronal cells, and endothelial cells, as well as in some T lymphocytes. CD200 involves inhibitory signaling, which prevents or reduces the expression of genes involved in inflammatory responses. CD200 can work in synergy with its natural receptor CD200R to activate immunosuppressive signaling cascades.

[0206] Without wishing to be bound by a particular theory, in some cases, CD200R does not contain any immunoreceptor tyrosine-based inhibitory motifs (ITIMs), which are commonly found in a large number of inhibitory receptors and can mediate their inhibitory effects through the recruitment of protein tyrosine phosphatases (such as Src homology 2 domain-containing phosphatase (SHP) 1, SH2, or inositol phosphatases (SHIP)) after phosphorylation. In contrast, in some cases, the molecular signaling mechanism of CD200R after activation involves direct interaction of adaptor proteins downstream of tyrosine kinase (Dok2) with CD200R membrane distal tyrosine residues located within the phosphotyrosine binding (PTB) domain recognition motif (NPxY). This interaction can lead to the binding and recruitment of RAS p21 protein activator (RasGAP), a protein containing an SH2 domain. The formation of the Dok2-RasGAP complex can inhibit Ras activation, thereby inhibiting other downstream inflammatory signals by inhibiting major mitogen-activated protein kinases, including phosphoinositide 3-kinase (PI3K) and extracellular signal-regulated kinase (Erk). In some cases, the interaction between CD200 and CD200R induces phosphorylation of tyrosine residues, thereby initiating a signal transduction cascade that recruits SHIP and RasGAP. Dok2 can be regulated by Dok1 through Crk-like (CrkL)-RasGAP inhibition; both Dok2 and Dok1 can be recruited during the CD200-CD200R interaction, which can lead to the recruitment of inositol phosphatases containing RasGAP and SH2. In some cases, Dok1 activation is initiated by binding to one of the three phosphotyrosine residues on the cytoplasmic amino acid chain of CD200R. This Dok1-phosphotyrosine binding can then inhibit the effect of Dok2 on Ras by activating CrkL.

[0207] In some aspects, provided herein are antibodies, compositions, nucleic acids, vectors, host cells, kits, uses thereof, and methods for their preparation that circumvent some of the aforementioned and other problems known in the art associated with existing anti-CD200R antibodies. In some embodiments, provided herein are CD200R agonist antibodies that enhance CD200R signaling by binding to CD200R on immune cells without competing with CD200.

[0208] Antibody sequences

[0209] In the present disclosure, compositions, therapeutic agents, kits, vectors, nucleic acid sequences, manufacture, culture and / or methods for producing CD200R agonistic antibodies or antigen-binding fragments or functional fragments thereof are provided herein, which enhance the biological effects of CD200R activation, for example, inhibiting the activity or proliferation of immune cells expressing CD200R molecules bound by antibodies, or promoting the downregulation of immune cell responses and inflammatory responses expressing CD200R. In some cases, CD200R agonistic antibodies promote downstream signaling of CD200R triggered by CD200 binding. In some cases, CD200R agonistic antibodies enhance the interaction between CD200 and CD200R. In some cases, CD200R agonistic antibodies promote downstream signaling of CD200R without increasing or enhancing the interaction between CD200 and CD200R. In some cases, CD200R agonistic antibodies activate or enhance CD200R signaling in the absence of CD200 binding to CD200R.

[0210] In some embodiments, the antibodies or antigen-binding fragments (eg, isolated antibodies) provided herein specifically bind to CD200R and enhance the CD200R signaling pathway of cells expressing CD200R on their surface.

[0211] In some embodiments, the antibodies or antigen-binding fragments (e.g., isolated antibodies) provided herein are CD200R antibodies comprising heavy chains. In some embodiments, the antibodies or antigen-binding fragments provided herein are CD200R antibodies comprising light chains. In some embodiments, the antibodies or antigen-binding fragments provided herein are CD200R antibodies comprising Fc regions.

[0212] In some embodiments, the heavy chain further comprises at least one heavy chain complementarity determining region (CDR). In some embodiments, the heavy chain CDR comprises a sequence as shown in any one of SEQ ID NO: 3, 4, 41, 5, 11, 12, 13, 19, 20, 21, 27, 28, 29, 35, 36, 36, 69, 70, or 92 with 0 to 3 amino acid modifications. In some embodiments, the heavy chain CDR comprises a sequence as shown in any one of SEQ ID NO: 3, 4, 41, 5, 11, 12, 13, 19, 20, 21, 27, 28, 29, 35, 36, 36, 69, 70, or 92 with 0 to 2 amino acid modifications. In some embodiments, the heavy chain CDR comprises a sequence as shown in any one of SEQ ID NOs: 3, 4, 41, 5, 11, 12, 13, 19, 20, 21, 27, 28, 29, 35, 36, 36, 69, 70, or 92 with 0 to 1 amino acid modifications.

[0213] In some embodiments, the heavy chain comprises a heavy chain variable region. In some cases, the heavy chain variable region comprises a heavy chain complementary determining region 1 (CDRH1), CDRH2 and CDRH3. In some cases, CDRH1, CDRH2 and CDRH3 respectively comprise the sequences shown in SEQ ID NO: 3, 41 and 70, each with 0 to 3 amino acid modifications, such as 0, 1, 2 or 3 modifications. In some cases, CDRH1, CDRH2 and CDRH3 respectively comprise the sequences shown in SEQ ID NO: 3, 41 and 5, each with 0 to 3 amino acid modifications, such as 0, 1, 2 or 3 modifications. In some cases, CDRH1, CDRH2 and CDRH3 respectively comprise the sequences shown in SEQ ID NO: 3, 4 and 5, each with 0 to 3 amino acid modifications, such as 0, 1, 2 or 3 modifications. In some cases, CDRH1, CDRH2 and CDRH3 comprise the sequences shown in SEQ ID NOs: 3, 41 and 5, respectively, each with 0 to 3 amino acid modifications, such as 0, 1, 2 or 3 modifications. In some cases, CDRH1, CDRH2 and CDRH3 comprise the sequences shown in SEQ ID NOs: 11, 12 and 13, respectively, each with 0 to 3 amino acid modifications, such as 0, 1, 2 or 3 modifications. In some cases, CDRH1, CDRH2 and CDRH3 comprise the sequences shown in SEQ ID NOs: 19, 20 and 21, respectively, each with 0 to 3 amino acid modifications, such as 0, 1, 2 or 3 modifications. In some cases, CDRH1, CDRH2 and CDRH3 comprise the sequences shown in SEQ ID NOs: 27, 28 and 29, respectively, each with 0 to 3 amino acid modifications, such as 0, 1, 2 or 3 modifications. In some cases, CDRH1, CDRH2, and CDRH3 comprise the sequences shown in SEQ ID NOs: 35, 36, and 37, respectively, each having 0 to 3 amino acid modifications, such as 0, 1, 2, or 3 modifications.

[0214] In some embodiments, the light chain further comprises at least one light chain complementary determining region (CDR). In some embodiments, the light chain CDR comprises a sequence as shown in any one of SEQ ID NO: 6, 7, 8, 14, 15, 16, 22, 23, 24, 30, 31, 32, 38, 39, 40, 67, 68 or 87 to 91 with 0 to 3 amino acid modifications. In some embodiments, the light chain CDR comprises a sequence as shown in any one of SEQ ID NO: 6, 7, 8, 14, 15, 16, 22, 23, 24, 30, 31, 32, 38, 39, 40, 67, 68 or 87 to 91 with 0 to 2 amino acid modifications. In some embodiments, the light chain CDR comprises a sequence as shown in any one of SEQ ID NOs: 6, 7, 8, 14, 15, 16, 22, 23, 24, 30, 31, 32, 38, 39, 40, 67, 68, or 87 to 91 with 0 to 1 amino acid modifications.

[0215] In some embodiments, the heavy chain comprises a light chain variable region. In some cases, the light chain variable region comprises a light chain complementary determining region 1 (CDRL1), CDRL2 and CDRL3. In some cases, CDRL1, CDRL2 and CDRL3 respectively comprise the sequences shown in SEQ ID NO: 6, 7 and 8, each with 0 to 3 amino acid modifications, such as 0, 1, 2 or 3 modifications. In some cases, CDRL1, CDRL2 and CDRL3 respectively comprise the sequences shown in SEQ ID NO: 6, 67 and 8, each with 0 to 3 amino acid modifications, such as 0, 1, 2 or 3 modifications. In some cases, CDRL1, CDRL2 and CDRL3 respectively comprise the sequences shown in SEQ ID NO: 6, 68 and 8, each with 0 to 3 amino acid modifications, such as 0, 1, 2 or 3 modifications. In some cases, CDRL1, CDRL2, and CDRL3 comprise the sequences shown in SEQ ID NOs: 14, 15, and 16, respectively, each with 0 to 3 amino acid modifications, such as 0, 1, 2, or 3 modifications. In some cases, CDRL1, CDRL2, and CDRL3 comprise the sequences shown in SEQ ID NOs: 22, 23, and 24, respectively, each with 0 to 3 amino acid modifications, such as 0, 1, 2, or 3 modifications. In some cases, CDRL1, CDRL2, and CDRL3 comprise the sequences shown in SEQ ID NOs: 30, 31, and 32, respectively, each with 0 to 3 amino acid modifications, such as 0, 1, 2, or 3 modifications. In some cases, CDRL1, CDRL2, and CDRL3 comprise the sequences shown in SEQ ID NOs: 38, 39, and 40, respectively, each with 0 to 3 amino acid modifications, such as 0, 1, 2, or 3 modifications. In some cases, CDRL1, CDRL2, and CDRL3 comprise the sequences shown in SEQ ID NOs: 6, 7, and 8, respectively, each with 0 to 2 amino acid modifications. In some cases, CDRL1, CDRL2, and CDRL3 comprise the sequences shown in SEQ ID NOs: 6, 67, and 8, respectively, each with 0 to 2 amino acid modifications. In some cases, CDRL1, CDRL2, and CDRL3 comprise the sequences shown in SEQ ID NOs: 6, 68, and 8, respectively, each with 0 to 2 amino acid modifications. In some cases, CDRL1, CDRL2, and CDRL3 comprise the sequences shown in SEQ ID NOs: 14, 15, and 16, respectively, each with 0 to 2 amino acid modifications. In some cases, CDRL1, CDRL2, and CDRL3 comprise the sequences shown in SEQ ID NOs: 22, 23, and 24, respectively, each with 0 to 2 amino acid modifications.In some cases, CDRL1, CDRL2, and CDRL3 comprise the sequences shown in SEQ ID NOs: 30, 31, and 32, respectively, each with 0 to 2 amino acid modifications. In some cases, CDRL1, CDRL2, and CDRL3 comprise the sequences shown in SEQ ID NOs: 38, 39, and 40, respectively, each with 0 to 2 amino acid modifications. In some cases, CDRL1, CDRL2, and CDRL3 comprise the sequences shown in SEQ ID NOs: 14, 15, and 16, respectively, each with 0 to 2 amino acid modifications. In some cases, CDRL1, CDRL2, and CDRL3 comprise the sequences shown in SEQ ID NOs: 22, 23, and 24, respectively, each with 0 to 1 amino acid modifications. In some cases, CDRL1, CDRL2, and CDRL3 comprise the sequences shown in SEQ ID NOs: 30, 31, and 32, respectively, each with 0 to 1 amino acid modifications. In some cases, CDRL1, CDRL2, and CDRL3 comprise the sequences set forth in SEQ ID NOs: 38, 39, and 40, respectively, each having 0 to 1 amino acid modifications.

[0216] In some embodiments, the antibodies provided herein (or antigen-binding fragments, hereinafter referred to as "antibodies", to refer to full-length antibodies or antigen-binding fragments of antibodies provided herein) comprise: a heavy chain comprising at least one heavy chain CDR as shown in any one of SEQ ID NOs: 3, 4, 41, 5, 69, or 70 with 0 to 3 amino acid modifications, and a light chain comprising at least one light chain CDR as shown in any one of SEQ ID NOs: 6, 7, or 8 with 0 to 3 amino acid modifications. In some cases, the antibodies provided herein comprise: a heavy chain comprising at least one heavy chain CDR as shown in any one of SEQ ID NOs: 3, 4, 41, 5, 69, or 70 with 0 to 3 amino acid modifications, and a light chain comprising at least one light chain CDR as shown in any one of SEQ ID NOs: 6, 67, or 8 with 0 to 3 amino acid modifications. In some cases, the antibodies provided herein comprise: a heavy chain comprising at least one heavy chain CDR as set forth in any one of SEQ ID NOs: 3, 4, 41, 5, 69, or 70 having 0 to 3 amino acid modifications, and a light chain comprising at least one light chain CDR as set forth in any one of SEQ ID NOs: 6, 68, or 8 having 0 to 3 amino acid modifications. In some cases, the antibodies provided herein comprise: a heavy chain comprising at least one heavy chain CDR as set forth in any one of SEQ ID NOs: 3, 41, or 70 having 0 to 3 amino acid modifications, and a light chain comprising at least one light chain CDR as set forth in any one of SEQ ID NOs: 6, 67, or 8 having 0 to 3 amino acid modifications. In some cases, the antibodies provided herein comprise: a heavy chain comprising at least one heavy chain CDR as set forth in any one of SEQ ID NOs: 3, 41, or 69 having 0 to 3 amino acid modifications, and a light chain comprising at least one light chain CDR as set forth in any one of SEQ ID NOs: 6, 67, or 8 having 0 to 3 amino acid modifications. In some cases, the antibodies provided herein comprise: a heavy chain comprising at least one heavy chain CDR as set forth in any one of SEQ ID NOs: 11, 12, or 13 having 0 to 3 amino acid modifications, and a light chain comprising at least one light chain CDR as set forth in any one of SEQ ID NOs: 14, 15, or 16 having 0 to 3 amino acid modifications. In some cases, the antibodies provided herein comprise: a heavy chain comprising at least one heavy chain CDR as set forth in any one of SEQ ID NOs: 19, 20, or 21 having 0 to 3 amino acid modifications, and a light chain comprising at least one light chain CDR as set forth in any one of SEQ ID NOs: 22, 23, or 24 having 0 to 3 amino acid modifications.In some cases, the antibodies provided herein comprise: a heavy chain comprising at least one heavy chain CDR as set forth in any one of SEQ ID NOs: 27, 28, or 29 having 0 to 3 amino acid modifications, and a light chain comprising at least one light chain CDR as set forth in any one of SEQ ID NOs: 30, 31, or 32 having 0 to 3 amino acid modifications. In some cases, the antibodies provided herein comprise: a heavy chain comprising at least one heavy chain CDR as set forth in any one of SEQ ID NOs: 35, 36, or 37 having 0 to 3 amino acid modifications, and a light chain comprising at least one light chain CDR as set forth in any one of SEQ ID NOs: 38, 39, or 40 having 0 to 3 amino acid modifications.

[0217] In some cases, the antibodies provided herein comprise: a heavy chain comprising at least one heavy chain CDR as set forth in any one of SEQ ID NOs: 3, 4, 41, 5, 69, or 70 having 0 to 2 amino acid modifications, and a light chain comprising at least one light chain CDR as set forth in any one of SEQ ID NOs: 6, 7, or 8 having 0 to 2 amino acid modifications. In some cases, the antibodies provided herein comprise: a heavy chain comprising at least one heavy chain CDR as set forth in any one of SEQ ID NOs: 3, 4, 41, 5, 69, or 70 having 0 to 2 amino acid modifications, and a light chain comprising at least one light chain CDR as set forth in any one of SEQ ID NOs: 6, 67, or 8 having 0 to 2 amino acid modifications. In some cases, the antibodies provided herein comprise: a heavy chain comprising at least one heavy chain CDR as set forth in any one of SEQ ID NOs: 3, 4, 41, 5, 69, or 70 having 0 to 2 amino acid modifications, and a light chain comprising at least one light chain CDR as set forth in any one of SEQ ID NOs: 6, 68, or 8 having 0 to 2 amino acid modifications. In some cases, the antibodies provided herein comprise: a heavy chain comprising at least one heavy chain CDR as set forth in any one of SEQ ID NOs: 11, 12, or 13 having 0 to 2 amino acid modifications, and a light chain comprising at least one light chain CDR as set forth in any one of SEQ ID NOs: 14, 15, or 16 having 0 to 2 amino acid modifications. In some cases, the antibodies provided herein comprise: a heavy chain comprising at least one heavy chain CDR as set forth in any one of SEQ ID NOs: 19, 20, or 21 having 0 to 2 amino acid modifications, and a light chain comprising at least one light chain CDR as set forth in any one of SEQ ID NOs: 22, 23, or 24 having 0 to 2 amino acid modifications. In some cases, the antibodies provided herein comprise: a heavy chain comprising at least one heavy chain CDR as set forth in any one of SEQ ID NOs: 27, 28, or 29 having 0 to 2 amino acid modifications, and a light chain comprising at least one light chain CDR as set forth in any one of SEQ ID NOs: 30, 31, or 32 having 0 to 2 amino acid modifications. In some cases, the antibodies provided herein comprise: a heavy chain comprising at least one heavy chain CDR as set forth in any one of SEQ ID NOs: 35, 36, or 37 having 0 to 2 amino acid modifications, and a light chain comprising at least one light chain CDR as set forth in any one of SEQ ID NOs: 38, 39, or 40 having 0 to 2 amino acid modifications.

[0218] In some cases, the antibodies provided herein comprise: a heavy chain comprising at least one heavy chain CDR as set forth in any one of SEQ ID NOs: 3, 4, 41, 5, 69, or 70 having 0 to 2 amino acid modifications, and a light chain comprising at least one light chain CDR as set forth in any one of SEQ ID NOs: 6, 7, or 8 having 0 to 1 amino acid modifications. In some cases, the antibodies provided herein comprise: a heavy chain comprising at least one heavy chain CDR as set forth in any one of SEQ ID NOs: 3, 4, 41, 5, 69, or 70 having 0 to 2 amino acid modifications, and a light chain comprising at least one light chain CDR as set forth in any one of SEQ ID NOs: 6, 67, or 8 having 0 to 1 amino acid modifications. In some cases, the antibodies provided herein comprise: a heavy chain comprising at least one heavy chain CDR as set forth in any one of SEQ ID NOs: 3, 4, 41, 5, 69, or 70 having 0 to 2 amino acid modifications, and a light chain comprising at least one light chain CDR as set forth in any one of SEQ ID NOs: 6, 68, or 8 having 0 to 1 amino acid modifications. In some cases, the antibodies provided herein comprise: a heavy chain comprising at least one heavy chain CDR as set forth in any one of SEQ ID NOs: 11, 12, or 13 having 0 to 1 amino acid modifications, and a light chain comprising at least one light chain CDR as set forth in any one of SEQ ID NOs: 14, 15, or 16 having 0 to 1 amino acid modifications. In some cases, the antibodies provided herein comprise: a heavy chain comprising at least one heavy chain CDR as set forth in any one of SEQ ID NOs: 19, 20, or 21 having 0 to 1 amino acid modifications, and a light chain comprising at least one light chain CDR as set forth in any one of SEQ ID NOs: 22, 23, or 24 having 0 to 1 amino acid modifications. In some cases, the antibodies provided herein comprise: a heavy chain comprising at least one heavy chain CDR as set forth in any one of SEQ ID NOs: 27, 28, or 29 having 0 to 1 amino acid modifications, and a light chain comprising at least one light chain CDR as set forth in any one of SEQ ID NOs: 30, 31, or 32 having 0 to 1 amino acid modifications. In some cases, the antibodies provided herein comprise: a heavy chain comprising at least one heavy chain CDR as set forth in any one of SEQ ID NOs: 35, 36, or 37 having 0 to 1 amino acid modifications, and a light chain comprising at least one light chain CDR as set forth in any one of SEQ ID NOs: 38, 39, or 40 having 0 to 1 amino acid modifications.

[0219] In some embodiments, the antibodies provided herein comprise a heavy chain and a light chain, the heavy chain comprising a heavy chain variable region further comprising a heavy chain complementary determining region 1 (CDRH1), CDRH2 and CDRH3, the light chain comprising a light chain variable region comprising a light chain complementary determining region 1 (CDRL1), CDRL2 and CDRL3, wherein CDRL1, CDRL2 and CDRL3. In some cases, CDRH1, CDRH2 and CDRH3 comprise the sequences shown in SEQ ID NOs: 3, 4 and 5, respectively, each having 0 to 3 amino acid modifications, such as 0, 1, 2 or 3 modifications, and CDRL1, CDRL2 and CDRL3 comprise the sequences shown in SEQ ID NOs: 6, 7 and 8, respectively, each having 0 to 3 amino acid modifications, such as 0, 1, 2 or 3 modifications. In some cases, CDRH1, CDRH2, and CDRH3 comprise the sequences set forth in SEQ ID NOs: 3, 4, and 5, respectively, each with 0 to 3 amino acid modifications, such as 0, 1, 2, or 3 modifications, and CDRL1, CDRL2, and CDRL3 comprise the sequences set forth in SEQ ID NOs: 6, 67, and 8, respectively, each with 0 to 3 amino acid modifications, such as 0, 1, 2, or 3 modifications. In some cases, CDRH1, CDRH2, and CDRH3 comprise the sequences set forth in SEQ ID NOs: 3, 41, 69, respectively, each with 0 to 3 amino acid modifications, such as 0, 1, 2, or 3 modifications, and CDRL1, CDRL2, and CDRL3 comprise the sequences set forth in SEQ ID NOs: 6, 67, and 8, respectively, each with 0 to 3 amino acid modifications, such as 0, 1, 2, or 3 modifications. In some cases, CDRH1, CDRH2, and CDRH3 comprise the sequences shown in SEQ ID NOs: 3, 41, 70, respectively, each with 0 to 3 amino acid modifications, such as 0, 1, 2, or 3 modifications, and CDRL1, CDRL2, and CDRL3 comprise the sequences shown in SEQ ID NOs: 6, 67, and 8, respectively, each with 0 to 3 amino acid modifications, such as 0, 1, 2, or 3 modifications. In some cases, CDRH1, CDRH2, and CDRH3 comprise the sequences shown in SEQ ID NOs: 3, 4, and 5, respectively, each with 0 to 3 amino acid modifications, such as 0, 1, 2, or 3 modifications, and CDRL1, CDRL2, and CDRL3 comprise the sequences shown in SEQ ID NOs: 6, 68, and 8, respectively, each with 0 to 3 amino acid modifications, such as 0, 1, 2, or 3 modifications.In some cases, CDRH1, CDRH2, and CDRH3 comprise the sequences set forth in SEQ ID NOs: 3, 41, and 5, respectively, each having 0 to 3 amino acid modifications, such as 0, 1, 2, or 3 modifications, and CDRL1, CDRL2, and CDRL3 comprise the sequences set forth in SEQ ID NOs: 6, 7, and 8, respectively, each having 0 to 3 amino acid modifications, such as 0, 1, 2, or 3 modifications. In some cases, CDRH1, CDRH2, and CDRH3 comprise the sequences set forth in SEQ ID NOs: 3, 41, and 5, respectively, each having 0 to 3 amino acid modifications, such as 0, 1, 2, or 3 modifications, and CDRL1, CDRL2, and CDRL3 comprise the sequences set forth in SEQ ID NOs: 6, 67, and 8, respectively, each having 0 to 3 amino acid modifications, such as 0, 1, 2, or 3 modifications. In some cases, CDRH1, CDRH2, and CDRH3 comprise the sequences set forth in SEQ ID NOs: 3, 41, and 5, respectively, each with 0 to 3 amino acid modifications, such as 0, 1, 2, or 3 modifications, and CDRL1, CDRL2, and CDRL3 comprise the sequences set forth in SEQ ID NOs: 6, 68, and 8, respectively, each with 0 to 3 amino acid modifications, such as 0, 1, 2, or 3 modifications. In some cases, CDRH1, CDRH2, and CDRH3 comprise the sequences set forth in SEQ ID NOs: 11, 12, and 13, respectively, each with 0 to 3 amino acid modifications, such as 0, 1, 2, or 3 modifications, and CDRL1, CDRL2, and CDRL3 comprise the sequences set forth in SEQ ID NOs: 14, 15, and 16, respectively, each with 0 to 3 amino acid modifications, such as 0, 1, 2, or 3 modifications. In some cases, CDRH1, CDRH2, and CDRH3 comprise the sequences set forth in SEQ ID NOs: 19, 20, and 21, respectively, each with 0 to 3 amino acid modifications, such as 0, 1, 2, or 3 modifications, and CDRL1, CDRL2, and CDRL3 comprise the sequences set forth in SEQ ID NOs: 22, 23, and 24, respectively, each with 0 to 3 amino acid modifications, such as 0, 1, 2, or 3 modifications. In some cases, CDRH1, CDRH2, and CDRH3 comprise the sequences set forth in SEQ ID NOs: 27, 28, and 29, respectively, each with 0 to 3 amino acid modifications, such as 0, 1, 2, or 3 modifications, and CDRL1, CDRL2, and CDRL3 comprise the sequences set forth in SEQ ID NOs: 30, 31, and 32, respectively, each with 0 to 3 amino acid modifications, such as 0, 1, 2, or 3 modifications.In some cases, CDRH1, CDRH2, and CDRH3 comprise the sequences shown in SEQ ID NOs:35, 36, and 37, respectively, each having 0 to 3 amino acid modifications, such as 0, 1, 2, or 3 modifications, and CDRL1, CDRL2, and CDRL3 comprise the sequences shown in SEQ ID NOs:38, 39, and 40, respectively, each having 0 to 3 amino acid modifications, such as 0, 1, 2, or 3 modifications.

[0220] In some cases, CDRH1, CDRH2, and CDRH3 comprise the sequences set forth in SEQ ID NOs: 3, 4, and 5, respectively, each with 0 to 2 amino acid modifications and CDRL1, CDRL2, and CDRL3 comprise the sequences set forth in SEQ ID NOs: 6, 7, and 8, respectively, each with 0 to 2 amino acid modifications. In some cases, CDRH1, CDRH2, and CDRH3 comprise the sequences set forth in SEQ ID NOs: 3, 4, and 5, respectively, each with 0 to 2 amino acid modifications and CDRL1, CDRL2, and CDRL3 comprise the sequences set forth in SEQ ID NOs: 6, 67, and 8, respectively, each with 0 to 2 amino acid modifications. In some cases, CDRH1, CDRH2, and CDRH3 comprise the sequences set forth in SEQ ID NOs: 3, 41, 69, respectively, each with 0 to 2 amino acid modifications and CDRL1, CDRL2, and CDRL3 comprise the sequences set forth in SEQ ID NOs: 6, 67, and 8, respectively, each with 0 to 2 amino acid modifications. In some cases, CDRH1, CDRH2, and CDRH3 comprise the sequences set forth in SEQ ID NOs: 3, 41, 70, respectively, each with 0 to 2 amino acid modifications and CDRL1, CDRL2, and CDRL3 comprise the sequences set forth in SEQ ID NOs: 6, 67, and 8, respectively, each with 0 to 2 amino acid modifications. In some cases, CDRH1, CDRH2, and CDRH3 comprise the sequences set forth in SEQ ID NOs: 3, 4, and 5, respectively, each with 0 to 2 amino acid modifications and CDRL1, CDRL2, and CDRL3 comprise the sequences set forth in SEQ ID NOs: 6, 68, and 8, respectively, each with 0 to 2 amino acid modifications. In some cases, CDRH1, CDRH2, and CDRH3 comprise the sequences set forth in SEQ ID NOs: 3, 41, and 5, respectively, each with 0 to 2 amino acid modifications and CDRL1, CDRL2, and CDRL3 comprise the sequences set forth in SEQ ID NOs: 6, 7, and 8, respectively, each with 0 to 2 amino acid modifications. In some cases, CDRH1, CDRH2, and CDRH3 comprise the sequences set forth in SEQ ID NOs: 3, 41, and 5, respectively, each with 0 to 2 amino acid modifications and CDRL1, CDRL2, and CDRL3 comprise the sequences set forth in SEQ ID NOs: 6, 67, and 8, respectively, each with 0 to 2 amino acid modifications. In some cases, CDRH1, CDRH2, and CDRH3 comprise the sequences set forth in SEQ ID NOs: 3, 41, and 5, respectively, each with 0 to 2 amino acid modifications and CDRL1, CDRL2, and CDRL3 comprise the sequences set forth in SEQ ID NOs: 6, 68, and 8, respectively, each with 0 to 2 amino acid modifications.In some cases, CDRH1, CDRH2, and CDRH3 comprise the sequences set forth in SEQ ID NOs: 11, 12, and 13, respectively, each with 0 to 2 amino acid modifications and CDRL1, CDRL2, and CDRL3 comprise the sequences set forth in SEQ ID NOs: 14, 15, and 16, respectively, each with 0 to 2 amino acid modifications. In some cases, CDRH1, CDRH2, and CDRH3 comprise the sequences set forth in SEQ ID NOs: 19, 20, and 21, respectively, each with 0 to 2 amino acid modifications and CDRL1, CDRL2, and CDRL3 comprise the sequences set forth in SEQ ID NOs: 22, 23, and 24, respectively, each with 0 to 2 amino acid modifications. In some cases, CDRH1, CDRH2, and CDRH3 comprise the sequences set forth in SEQ ID NOs: 27, 28, and 29, respectively, each with 0 to 2 amino acid modifications and CDRL1, CDRL2, and CDRL3 comprise the sequences set forth in SEQ ID NOs: 30, 31, and 32, respectively, each with 0 to 2 amino acid modifications. In some cases, CDRH1, CDRH2, and CDRH3 comprise the sequences set forth in SEQ ID NOs:35, 36, and 37, respectively, each having 0 to 2 amino acid modifications and CDRL1, CDRL2, and CDRL3 comprise the sequences set forth in SEQ ID NOs:38, 39, and 40, respectively, each having 0 to 2 amino acid modifications.

[0221] In some cases, CDRH1, CDRH2, and CDRH3 comprise the sequences set forth in SEQ ID NOs: 3, 4, and 5, respectively, each with 0 to 1 amino acid modifications and CDRL1, CDRL2, and CDRL3 comprise the sequences set forth in SEQ ID NOs: 6, 7, and 8, respectively, each with 0 to 1 amino acid modifications. In some cases, CDRH1, CDRH2, and CDRH3 comprise the sequences set forth in SEQ ID NOs: 3, 4, and 5, respectively, each with 0 to 1 amino acid modifications and CDRL1, CDRL2, and CDRL3 comprise the sequences set forth in SEQ ID NOs: 6, 67, and 8, respectively, each with 0 to 1 amino acid modifications. In some cases, CDRH1, CDRH2, and CDRH3 comprise the sequences set forth in SEQ ID NOs: 3, 41, 69, respectively, each with 0 to 1 amino acid modifications and CDRL1, CDRL2, and CDRL3 comprise the sequences set forth in SEQ ID NOs: 6, 67, and 8, respectively, each with 0 to 1 amino acid modifications. In some cases, CDRH1, CDRH2, and CDRH3 comprise the sequences set forth in SEQ ID NOs: 3, 41, 70, respectively, each with 0 to 1 amino acid modification and CDRL1, CDRL2, and CDRL3 comprise the sequences set forth in SEQ ID NOs: 6, 67, and 8, respectively, each with 0 to 1 amino acid modification. In some cases, CDRH1, CDRH2, and CDRH3 comprise the sequences set forth in SEQ ID NOs: 3, 4, and 5, respectively, each with 0 to 1 amino acid modification and CDRL1, CDRL2, and CDRL3 comprise the sequences set forth in SEQ ID NOs: 6, 68, and 8, respectively, each with 0 to 1 amino acid modification. In some cases, CDRH1, CDRH2, and CDRH3 comprise the sequences set forth in SEQ ID NOs: 3, 41, and 5, respectively, each with 0 to 1 amino acid modification and CDRL1, CDRL2, and CDRL3 comprise the sequences set forth in SEQ ID NOs: 6, 7, and 8, respectively, each with 0 to 1 amino acid modification. In some cases, CDRH1, CDRH2, and CDRH3 comprise the sequences set forth in SEQ ID NOs: 3, 41, and 5, respectively, each having 0 to 1 amino acid modifications and CDRL1, CDRL2, and CDRL3 comprise the sequences set forth in SEQ ID NOs: 6, 67, and 8, respectively, each having 0 to 1 amino acid modifications. In some cases, CDRH1, CDRH2, and CDRH3 comprise the sequences set forth in SEQ ID NOs: 3, 41, and 5, respectively, each having 0 to 1 amino acid modifications and CDRL1, CDRL2, and CDRL3 comprise the sequences set forth in SEQ ID NOs: 6, 68, and 8, respectively, each having 0 to 1 amino acid modifications.In some cases, CDRH1, CDRH2, and CDRH3 comprise the sequences set forth in SEQ ID NOs: 11, 12, and 13, respectively, each with 0 to 1 amino acid modifications and CDRL1, CDRL2, and CDRL3 comprise the sequences set forth in SEQ ID NOs: 14, 15, and 16, respectively, each with 0 to 1 amino acid modifications. In some cases, CDRH1, CDRH2, and CDRH3 comprise the sequences set forth in SEQ ID NOs: 19, 20, and 21, respectively, each with 0 to 1 amino acid modifications and CDRL1, CDRL2, and CDRL3 comprise the sequences set forth in SEQ ID NOs: 22, 23, and 24, respectively, each with 0 to 1 amino acid modifications. In some cases, CDRH1, CDRH2, and CDRH3 comprise the sequences set forth in SEQ ID NOs: 27, 28, and 29, respectively, each with 0 to 1 amino acid modifications and CDRL1, CDRL2, and CDRL3 comprise the sequences set forth in SEQ ID NOs: 30, 31, and 32, respectively, each with 0 to 1 amino acid modifications. In some cases, CDRH1, CDRH2, and CDRH3 comprise the sequences set forth in SEQ ID NOs:35, 36, and 37, respectively, each having 0 to 1 amino acid modifications and CDRL1, CDRL2, and CDRL3 comprise the sequences set forth in SEQ ID NOs:38, 39, and 40, respectively, each having 0 to 1 amino acid modifications.

[0222] In some embodiments, the antibodies provided herein comprise a heavy chain variable region comprising an amino acid sequence having at least 90% sequence identity to the amino acid sequence shown as SEQ ID NO: 1, 9, 17, 25, 33, 42, 43, 44, 45, 46, 47, 71, 72, or 93. In some embodiments, the antibodies provided herein comprise a heavy chain variable region comprising an amino acid sequence having at least 95% sequence identity to the amino acid sequence shown as SEQ ID NO: 1, 9, 17, 25, 33, 42, 43, 44, 45, 46, 47, 71, 72, or 93. In some embodiments, the antibodies provided herein comprise a heavy chain variable region comprising an amino acid sequence having at least 96% sequence identity to the amino acid sequence shown as SEQ ID NO: 1, 9, 17, 25, 33, 42, 43, 44, 45, 46, 47, 71, 72, or 93. In some embodiments, the antibodies provided herein comprise a heavy chain variable region comprising an amino acid sequence having at least 97% sequence identity to the amino acid sequence shown as SEQ ID NO: 1, 9, 17, 25, 33, 42, 43, 44, 45, 46, 47, 71, 72, or 93. In some embodiments, the antibodies provided herein comprise a heavy chain variable region comprising an amino acid sequence having at least 98% sequence identity to the amino acid sequence shown as SEQ ID NO: 1, 9, 17, 25, 33, 42, 43, 44, 45, 46, 47, 71, 72, or 93. In some embodiments, the antibodies provided herein comprise a heavy chain variable region comprising an amino acid sequence having at least 99% sequence identity to the amino acid sequence shown as SEQ ID NO: 1, 9, 17, 25, 33, 42, 43, 44, 45, 46, 47, 71, 72, or 93. In some embodiments, the antibodies provided herein comprise a heavy chain variable region comprising an amino acid sequence having 100% sequence identity to the amino acid sequence shown in SEQ ID NO: 1, 9, 17, 25, 33, 42, 43, 44, 45, 46, 47, 71, 72 or 93.

[0223] In some embodiments, the antibodies provided herein comprise a heavy chain variable region comprising an amino acid sequence as shown in SEQ ID NO: 1, 9, 17, 25, 33, 42, 43, 44, 45, 46, 47, 71, 72, or 93 with 0 to 3 amino acid modifications. In some embodiments, the antibodies provided herein comprise a heavy chain variable region comprising an amino acid sequence as shown in SEQ ID NO: 1, 9, 17, 25, 33, 42, 43, 44, 45, 46, 47, 71, 72, or 93 with 0 to 2 amino acid modifications. In some embodiments, the antibodies provided herein comprise a heavy chain variable region comprising an amino acid sequence as shown in SEQ ID NO: 1, 9, 17, 25, 33, 42, 43, 44, 45, 46, 47, 71, 72, or 93 with 0 to 2 amino acid modifications. In some embodiments, the antibodies provided herein comprise a heavy chain variable region comprising an amino acid sequence as shown in SEQ ID NO: 1, 9, 17, 25, 33, 42, 43, 44, 45, 46, 47, 71, 72 or 93 with 0 to 1 amino acid modification. In some embodiments, the antibodies provided herein comprise a heavy chain variable region comprising an amino acid sequence as shown in SEQ ID NO: 1, 9, 17, 25, 33, 42, 43, 44, 45, 46, 47, 71, 72 or 93.

[0224] In some embodiments, the antibodies provided herein comprise a light chain variable region comprising an amino acid sequence having at least 90% sequence identity to the amino acid sequence shown as SEQ ID NO: 2, 10, 18, 26, 34, 48, 49, 50, 51, 52, 65, 66, or 94. In some embodiments, the antibodies provided herein comprise a light chain variable region comprising an amino acid sequence having at least 95% sequence identity to the amino acid sequence shown as SEQ ID NO: 2, 10, 18, 26, 34, 48, 49, 50, 51, 52, 65, 66, or 94. In some embodiments, the antibodies provided herein comprise a light chain variable region comprising an amino acid sequence having at least 96% sequence identity to the amino acid sequence shown as SEQ ID NO: 2, 10, 18, 26, 34, 48, 49, 50, 51, 52, 65, 66, or 94. In some embodiments, the antibodies provided herein comprise a light chain variable region comprising an amino acid sequence having at least 97% sequence identity to the amino acid sequence shown as SEQ ID NO: 2, 10, 18, 26, 34, 48, 49, 50, 51, 52, 65, 66, or 94. In some embodiments, the antibodies provided herein comprise a light chain variable region comprising an amino acid sequence having at least 98% sequence identity to the amino acid sequence shown as SEQ ID NO: 2, 10, 18, 26, 34, 48, 49, 50, 51, 52, 65, 66, or 94. In some embodiments, the antibodies provided herein comprise a light chain variable region comprising an amino acid sequence having at least 99% sequence identity to the amino acid sequence shown as SEQ ID NO: 2, 10, 18, 26, 34, 48, 49, 50, 51, 52, 65, 66, or 94. In some embodiments, the antibodies provided herein comprise a light chain variable region comprising an amino acid sequence having 100% sequence identity to the amino acid sequence shown in SEQ ID NO: 2, 10, 18, 26, 34, 48, 49, 50, 51, 52, 65, 66 or 94.

[0225] In some embodiments, the antibodies provided herein comprise a light chain variable region comprising an amino acid sequence as shown in SEQ ID NO: 2, 10, 18, 26, 34, 48, 49, 50, 51, 52, 65, 66, or 94 with 0 to 3 amino acid modifications. In some embodiments, the antibodies provided herein comprise a light chain variable region comprising an amino acid sequence as shown in SEQ ID NO: 2, 10, 18, 26, 34, 48, 49, 50, 51, 52, 65, 66, or 94 with 0 to 2 amino acid modifications. In some embodiments, the antibodies provided herein comprise a light chain variable region comprising an amino acid sequence as shown in SEQ ID NO: 2, 10, 18, 26, 34, 48, 49, 50, 51, 52, 65, 66, or 94 with 0 to 1 amino acid modification. In some embodiments, the antibodies provided herein comprise a light chain variable region comprising the amino acid sequence shown in SEQ ID NO: 2, 10, 18, 26, 34, 48, 49, 50, 51, 52, 65, 66 or 94.

[0226] In some embodiments, the antibodies provided herein comprise a heavy chain variable region comprising an amino acid sequence having at least 90% sequence identity with the amino acid sequence shown in SEQ ID NO: 1, and a light chain variable region comprising an amino acid sequence having at least 90% sequence identity with the amino acid sequence shown in SEQ ID NO: 2. In some cases, the antibodies provided herein comprise a heavy chain variable region comprising an amino acid sequence having at least 95% sequence identity with the amino acid sequence shown in SEQ ID NO: 1, and a light chain variable region comprising an amino acid sequence having at least 95% sequence identity with the amino acid sequence shown in SEQ ID NO: 2. In some cases, the antibodies provided herein comprise a heavy chain variable region comprising an amino acid sequence having at least 96% sequence identity with the amino acid sequence shown in SEQ ID NO: 1, and a light chain variable region comprising an amino acid sequence having at least 96% sequence identity with the amino acid sequence shown in SEQ ID NO: 2. In some cases, the antibodies provided herein comprise a heavy chain variable region comprising an amino acid sequence having at least 97% sequence identity to the amino acid sequence set forth in SEQ ID NO: 1, and a light chain variable region comprising an amino acid sequence having at least 97% sequence identity to the amino acid sequence set forth in SEQ ID NO: 2. In some cases, the antibodies provided herein comprise a heavy chain variable region comprising an amino acid sequence having at least 98% sequence identity to the amino acid sequence set forth in SEQ ID NO: 1, and a light chain variable region comprising an amino acid sequence having at least 98% sequence identity to the amino acid sequence set forth in SEQ ID NO: 2. In some cases, the antibodies provided herein comprise a heavy chain variable region comprising an amino acid sequence having at least 99% sequence identity to the amino acid sequence set forth in SEQ ID NO: 1, and a light chain variable region comprising an amino acid sequence having at least 99% sequence identity to the amino acid sequence set forth in SEQ ID NO: 2. In some cases, the antibodies provided herein comprise a heavy chain variable region comprising an amino acid sequence having 100% sequence identity to the amino acid sequence shown in SEQ ID NO:1, and a light chain variable region comprising an amino acid sequence having 100% sequence identity to the amino acid sequence shown in SEQ ID NO:2.

[0227] In some embodiments, the antibodies provided herein comprise a heavy chain variable region comprising an amino acid sequence having at least 90% sequence identity to the amino acid sequence set forth in SEQ ID NO: 9, and a light chain variable region comprising an amino acid sequence having at least 90% sequence identity to the amino acid sequence set forth in SEQ ID NO: 10. In some cases, the antibodies provided herein comprise a heavy chain variable region comprising an amino acid sequence having at least 95% sequence identity to the amino acid sequence set forth in SEQ ID NO: 9, and a light chain variable region comprising an amino acid sequence having at least 95% sequence identity to the amino acid sequence set forth in SEQ ID NO: 10. In some cases, the antibodies provided herein comprise a heavy chain variable region comprising an amino acid sequence having at least 96% sequence identity to the amino acid sequence set forth in SEQ ID NO: 9, and a light chain variable region comprising an amino acid sequence having at least 96% sequence identity to the amino acid sequence set forth in SEQ ID NO: 10. In some cases, the antibodies provided herein comprise a heavy chain variable region comprising an amino acid sequence having at least 97% sequence identity to the amino acid sequence set forth in SEQ ID NO: 9, and a light chain variable region comprising an amino acid sequence having at least 97% sequence identity to the amino acid sequence set forth in SEQ ID NO: 10. In some cases, the antibodies provided herein comprise a heavy chain variable region comprising an amino acid sequence having at least 98% sequence identity to the amino acid sequence set forth in SEQ ID NO: 9, and a light chain variable region comprising an amino acid sequence having at least 98% sequence identity to the amino acid sequence set forth in SEQ ID NO: 10. In some cases, the antibodies provided herein comprise a heavy chain variable region comprising an amino acid sequence having at least 99% sequence identity to the amino acid sequence set forth in SEQ ID NO: 9, and a light chain variable region comprising an amino acid sequence having at least 99% sequence identity to the amino acid sequence set forth in SEQ ID NO: 10. In some cases, the antibodies provided herein comprise a heavy chain variable region comprising an amino acid sequence having 100% sequence identity to the amino acid sequence shown in SEQ ID NO:9 and a light chain variable region comprising an amino acid sequence having 100% sequence identity to the amino acid sequence shown in SEQ ID NO:10.

[0228] In some embodiments, the antibodies provided herein comprise a heavy chain variable region comprising an amino acid sequence having at least 90% sequence identity to the amino acid sequence set forth in SEQ ID NO: 17, and a light chain variable region comprising an amino acid sequence having at least 90% sequence identity to the amino acid sequence set forth in SEQ ID NO: 18. In some cases, the antibodies provided herein comprise a heavy chain variable region comprising an amino acid sequence having at least 95% sequence identity to the amino acid sequence set forth in SEQ ID NO: 17, and a light chain variable region comprising an amino acid sequence having at least 95% sequence identity to the amino acid sequence set forth in SEQ ID NO: 18. In some cases, the antibodies provided herein comprise a heavy chain variable region comprising an amino acid sequence having at least 96% sequence identity to the amino acid sequence set forth in SEQ ID NO: 17, and a light chain variable region comprising an amino acid sequence having at least 96% sequence identity to the amino acid sequence set forth in SEQ ID NO: 18. In some cases, the antibodies provided herein comprise a heavy chain variable region comprising an amino acid sequence having at least 97% sequence identity to the amino acid sequence set forth in SEQ ID NO: 17, and a light chain variable region comprising an amino acid sequence having at least 97% sequence identity to the amino acid sequence set forth in SEQ ID NO: 18. In some cases, the antibodies provided herein comprise a heavy chain variable region comprising an amino acid sequence having at least 98% sequence identity to the amino acid sequence set forth in SEQ ID NO: 17, and a light chain variable region comprising an amino acid sequence having at least 98% sequence identity to the amino acid sequence set forth in SEQ ID NO: 18. In some cases, the antibodies provided herein comprise a heavy chain variable region comprising an amino acid sequence having at least 99% sequence identity to the amino acid sequence set forth in SEQ ID NO: 17, and a light chain variable region comprising an amino acid sequence having at least 99% sequence identity to the amino acid sequence set forth in SEQ ID NO: 18. In some cases, the antibodies provided herein comprise a heavy chain variable region comprising an amino acid sequence having 100% sequence identity to the amino acid sequence set forth in SEQ ID NO:17, and a light chain variable region comprising an amino acid sequence having 100% sequence identity to the amino acid sequence set forth in SEQ ID NO:18.

[0229] In some embodiments, the antibodies provided herein comprise a heavy chain variable region comprising an amino acid sequence having at least 90% sequence identity to the amino acid sequence set forth in SEQ ID NO: 25, and a light chain variable region comprising an amino acid sequence having at least 90% sequence identity to the amino acid sequence set forth in SEQ ID NO: 26. In some cases, the antibodies provided herein comprise a heavy chain variable region comprising an amino acid sequence having at least 95% sequence identity to the amino acid sequence set forth in SEQ ID NO: 25, and a light chain variable region comprising an amino acid sequence having at least 95% sequence identity to the amino acid sequence set forth in SEQ ID NO: 26. In some cases, the antibodies provided herein comprise a heavy chain variable region comprising an amino acid sequence having at least 96% sequence identity to the amino acid sequence set forth in SEQ ID NO: 25, and a light chain variable region comprising an amino acid sequence having at least 96% sequence identity to the amino acid sequence set forth in SEQ ID NO: 26. In some cases, the antibodies provided herein comprise a heavy chain variable region comprising an amino acid sequence having at least 97% sequence identity to the amino acid sequence set forth in SEQ ID NO: 25, and a light chain variable region comprising an amino acid sequence having at least 97% sequence identity to the amino acid sequence set forth in SEQ ID NO: 26. In some cases, the antibodies provided herein comprise a heavy chain variable region comprising an amino acid sequence having at least 98% sequence identity to the amino acid sequence set forth in SEQ ID NO: 25, and a light chain variable region comprising an amino acid sequence having at least 98% sequence identity to the amino acid sequence set forth in SEQ ID NO: 26. In some cases, the antibodies provided herein comprise a heavy chain variable region comprising an amino acid sequence having at least 99% sequence identity to the amino acid sequence set forth in SEQ ID NO: 25, and a light chain variable region comprising an amino acid sequence having at least 99% sequence identity to the amino acid sequence set forth in SEQ ID NO: 26. In some cases, the antibodies provided herein comprise a heavy chain variable region comprising an amino acid sequence having 100% sequence identity to the amino acid sequence shown in SEQ ID NO:25, and a light chain variable region comprising an amino acid sequence having 100% sequence identity to the amino acid sequence shown in SEQ ID NO:26.

[0230] In some embodiments, the antibodies provided herein comprise a heavy chain variable region comprising an amino acid sequence having at least 90% sequence identity to the amino acid sequence set forth in SEQ ID NO: 33, and a light chain variable region comprising an amino acid sequence having at least 90% sequence identity to the amino acid sequence set forth in SEQ ID NO: 34. In some cases, the antibodies provided herein comprise a heavy chain variable region comprising an amino acid sequence having at least 95% sequence identity to the amino acid sequence set forth in SEQ ID NO: 33, and a light chain variable region comprising an amino acid sequence having at least 95% sequence identity to the amino acid sequence set forth in SEQ ID NO: 34. In some cases, the antibodies provided herein comprise a heavy chain variable region comprising an amino acid sequence having at least 96% sequence identity to the amino acid sequence set forth in SEQ ID NO: 33, and a light chain variable region comprising an amino acid sequence having at least 96% sequence identity to the amino acid sequence set forth in SEQ ID NO: 34. In some cases, the antibodies provided herein comprise a heavy chain variable region comprising an amino acid sequence having at least 97% sequence identity to the amino acid sequence set forth in SEQ ID NO: 33, and a light chain variable region comprising an amino acid sequence having at least 97% sequence identity to the amino acid sequence set forth in SEQ ID NO: 34. In some cases, the antibodies provided herein comprise a heavy chain variable region comprising an amino acid sequence having at least 98% sequence identity to the amino acid sequence set forth in SEQ ID NO: 33, and a light chain variable region comprising an amino acid sequence having at least 98% sequence identity to the amino acid sequence set forth in SEQ ID NO: 34. In some cases, the antibodies provided herein comprise a heavy chain variable region comprising an amino acid sequence having at least 99% sequence identity to the amino acid sequence set forth in SEQ ID NO: 33, and a light chain variable region comprising an amino acid sequence having at least 99% sequence identity to the amino acid sequence set forth in SEQ ID NO: 34. In some cases, the antibodies provided herein comprise a heavy chain variable region comprising an amino acid sequence having 100% sequence identity to the amino acid sequence shown in SEQ ID NO:33, and a light chain variable region comprising an amino acid sequence having 100% sequence identity to the amino acid sequence shown in SEQ ID NO:34.

[0231] In some embodiments, the antibodies provided herein comprise a heavy chain variable region comprising an amino acid sequence having at least 90% sequence identity to an amino acid sequence as shown in any one of SEQ ID NOs: 1, 42, 43, 44, 45, 46, 47, 71, 72, or 93, and a light chain variable region comprising an amino acid sequence having at least 90% sequence identity to an amino acid sequence as shown in any one of SEQ ID NOs: 2, 48, 49, 50, 51, 52, 65, 66, or 94. In some cases, the antibodies provided herein comprise a heavy chain variable region comprising an amino acid sequence having at least 95% sequence identity to the amino acid sequence shown in any one of SEQ ID NOs: 1, 42, 43, 44, 45, 46, 47, 71, 72, or 93, and a light chain variable region comprising an amino acid sequence having at least 95% sequence identity to the amino acid sequence shown in any one of SEQ ID NOs: 2, 48, 49, 50, 51, 52, 65, 66, or 94. In some cases, the antibodies provided herein comprise a heavy chain variable region comprising an amino acid sequence having at least 96% sequence identity to the amino acid sequence shown in any one of SEQ ID NOs: 1, 42, 43, 44, 45, 46, 47, 71, 72, or 93, and a light chain variable region comprising an amino acid sequence having at least 96% sequence identity to the amino acid sequence shown in any one of SEQ ID NOs: 2, 48, 49, 50, 51, 52, 65, 66, or 94. In some cases, the antibodies provided herein comprise a heavy chain variable region comprising an amino acid sequence having at least 97% sequence identity to the amino acid sequence shown in any one of SEQ ID NOs: 1, 42, 43, 44, 45, 46, 47, 71, 72, or 93, and a light chain variable region comprising an amino acid sequence having at least 97% sequence identity to the amino acid sequence shown in any one of SEQ ID NOs: 2, 48, 49, 50, 51, 52, 65, 66, or 94. In some cases, the antibodies provided herein comprise a heavy chain variable region comprising an amino acid sequence having at least 98% sequence identity to the amino acid sequence shown in any one of SEQ ID NOs: 1, 42, 43, 44, 45, 46, 47, 71, 72, or 93, and a light chain variable region comprising an amino acid sequence having at least 98% sequence identity to the amino acid sequence shown in any one of SEQ ID NOs: 2, 48, 49, 50, 51, 52, 65, 66, or 94.In some cases, the antibodies provided herein comprise a heavy chain variable region comprising an amino acid sequence having at least 99% sequence identity to the amino acid sequence shown in any one of SEQ ID NOs: 1, 42, 43, 44, 45, 46, 47, 71, 72, or 93, and a light chain variable region comprising an amino acid sequence having at least 99% sequence identity to the amino acid sequence shown in any one of SEQ ID NOs: 2, 48, 49, 50, 51, 52, 65, 66, or 94. In some cases, the antibodies provided herein comprise a heavy chain variable region comprising an amino acid sequence having 100% sequence identity to the amino acid sequence shown in any one of SEQ ID NOs: 1, 42, 43, 44, 45, 46, 47, 71, 72, or 93, and a light chain variable region comprising an amino acid sequence having 100% sequence identity to the amino acid sequence shown in any one of SEQ ID NOs: 2, 48, 49, 50, 51, 52, 65, 66, or 94.

[0232] In some cases, the antibodies provided herein comprise a heavy chain variable region comprising an amino acid sequence having at least 90% sequence identity to the amino acid sequence set forth in any one of SEQ ID NOs: 42, 43, 44, 45, 46, 47, 71, 72, or 93, and a light chain variable region comprising an amino acid sequence having at least 90% sequence identity to the amino acid sequence set forth in any one of SEQ ID NOs: 48, 49, 50, 51, 52, 65, 66, or 94. In some cases, the antibodies provided herein comprise a heavy chain variable region comprising an amino acid sequence having at least 95% sequence identity to the amino acid sequence set forth in any one of SEQ ID NOs: 42, 43, 44, 45, 46, 47, 71, 72, or 93, and a light chain variable region comprising an amino acid sequence having at least 95% sequence identity to the amino acid sequence set forth in any one of SEQ ID NOs: 48, 49, 50, 51, 52, 65, 66, or 94. In some cases, the antibodies provided herein comprise a heavy chain variable region comprising an amino acid sequence having at least 96% sequence identity to the amino acid sequence set forth in any one of SEQ ID NOs: 42, 43, 44, 45, 46, 47, 71, 72, or 93, and a light chain variable region comprising an amino acid sequence having at least 96% sequence identity to the amino acid sequence set forth in any one of SEQ ID NOs: 48, 49, 50, 51, 52, 65, 66, or 94. In some cases, the antibodies provided herein comprise a heavy chain variable region comprising an amino acid sequence having at least 97% sequence identity to the amino acid sequence set forth in any one of SEQ ID NOs: 42, 43, 44, 45, 46, 47, 71, 72, or 93, and a light chain variable region comprising an amino acid sequence having at least 97% sequence identity to the amino acid sequence set forth in any one of SEQ ID NOs: 48, 49, 50, 51, 52, 65, 66, or 94. In some cases, the antibodies provided herein comprise a heavy chain variable region comprising an amino acid sequence having at least 98% sequence identity to the amino acid sequence shown in any one of SEQ ID NOs:42, 43, 44, 45, 46, 47, 71, 72, or 93, and a light chain variable region comprising an amino acid sequence having at least 98% sequence identity to the amino acid sequence shown in any one of SEQ ID NOs:48, 49, 50, 51, 52, 65, 66, or 94.In some cases, the antibodies provided herein comprise a heavy chain variable region comprising an amino acid sequence having at least 99% sequence identity to the amino acid sequence shown in any one of SEQ ID NOs:42, 43, 44, 45, 46, 47, 71, 72, or 93, and a light chain variable region comprising an amino acid sequence having 100% sequence identity to the amino acid sequence shown in SEQ ID NOs:48, 49, 50, 51, 52, 65, 66, or 94.

[0233] In some cases, the antibodies provided herein comprise a heavy chain variable region comprising an amino acid sequence having at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence set forth in SEQ ID NO: 1, and a light chain variable region comprising an amino acid sequence having at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence set forth in SEQ ID NO: 2. In some cases, the antibodies provided herein comprise a heavy chain variable region comprising an amino acid sequence having at least 95% sequence identity to the amino acid sequence set forth in SEQ ID NO: 1, and a light chain variable region comprising an amino acid sequence having at least 95% sequence identity to the amino acid sequence set forth in SEQ ID NO: 2. In some cases, the antibodies provided herein comprise a heavy chain variable region comprising an amino acid sequence having at least 97% sequence identity to the amino acid sequence set forth in SEQ ID NO: 1, and a light chain variable region comprising an amino acid sequence having at least 97% sequence identity to the amino acid sequence set forth in SEQ ID NO: 2. In some cases, the antibodies provided herein comprise a heavy chain variable region comprising an amino acid sequence having at least 99% sequence identity to the amino acid sequence set forth in SEQ ID NO: 1, and a light chain variable region comprising an amino acid sequence having at least 99% sequence identity to the amino acid sequence set forth in SEQ ID NO: 2. In some cases, the antibodies provided herein comprise a heavy chain variable region comprising an amino acid sequence having 100% sequence identity to the amino acid sequence set forth in SEQ ID NO: 1, and a light chain variable region comprising an amino acid sequence having 100% sequence identity to the amino acid sequence set forth in SEQ ID NO: 2. In some cases, the antibodies provided herein comprise a heavy chain variable region comprising an amino acid sequence having less than or equal to 10, 9, 8, 7, 6, 5, 4, 3, 2, 1 or 0 total substitutions, deletions and / or insertions in the amino acid sequence set forth in SEQ ID NO:1, and a light chain variable region comprising an amino acid sequence having less than or equal to 10, 9, 8, 7, 6, 5, 4, 3, 2, 1 or 0 total substitutions, deletions and / or insertions in the amino acid sequence set forth in SEQ ID NO:2.In some cases, the antibodies provided herein comprise a heavy chain variable region comprising an amino acid sequence having less than or equal to 10 total substitutions, deletions and / or insertions in the amino acid sequence set forth in SEQ ID NO: 1, and a light chain variable region comprising an amino acid sequence having less than or equal to 10 total substitutions, deletions and / or insertions in the amino acid sequence set forth in SEQ ID NO: 2. In some cases, the antibodies provided herein comprise a heavy chain variable region comprising an amino acid sequence having less than or equal to 7 total substitutions, deletions and / or insertions in the amino acid sequence set forth in SEQ ID NO: 1, and a light chain variable region comprising an amino acid sequence having less than or equal to 7 total substitutions, deletions and / or insertions in the amino acid sequence set forth in SEQ ID NO: 2. In some cases, the antibodies provided herein comprise a heavy chain variable region comprising an amino acid sequence having less than or equal to 5 total substitutions, deletions and / or insertions in the amino acid sequence set forth in SEQ ID NO: 1, and a light chain variable region comprising an amino acid sequence having less than or equal to 5 total substitutions, deletions and / or insertions in the amino acid sequence set forth in SEQ ID NO: 2. In some cases, the antibodies provided herein comprise a heavy chain variable region comprising an amino acid sequence having less than or equal to 3 total substitutions, deletions and / or insertions in the amino acid sequence set forth in SEQ ID NO: 1, and a light chain variable region comprising an amino acid sequence having less than or equal to 3 total substitutions, deletions and / or insertions in the amino acid sequence set forth in SEQ ID NO: 2. In some cases, the antibodies provided herein comprise a heavy chain variable region comprising an amino acid sequence having less than or equal to 2 total substitutions, deletions and / or insertions in the amino acid sequence set forth in SEQ ID NO: 1, and a light chain variable region comprising an amino acid sequence having less than or equal to 2 total substitutions, deletions and / or insertions in the amino acid sequence set forth in SEQ ID NO: 2. In some cases, the antibodies provided herein comprise a heavy chain variable region comprising an amino acid sequence having less than or equal to 1 total substitution, deletion and / or insertion in the amino acid sequence set forth in SEQ ID NO: 1, and a light chain variable region comprising an amino acid sequence having less than or equal to 1 total substitution, deletion and / or insertion in the amino acid sequence set forth in SEQ ID NO: 2.

[0234] In some cases, the antibodies provided herein comprise a heavy chain variable region comprising an amino acid sequence having at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence set forth in SEQ ID NO: 1, and a light chain variable region comprising an amino acid sequence having at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence set forth in SEQ ID NO: 48. In some cases, the antibodies provided herein comprise a heavy chain variable region comprising an amino acid sequence having at least 95% sequence identity to the amino acid sequence set forth in SEQ ID NO: 1, and a light chain variable region comprising an amino acid sequence having at least 95% sequence identity to the amino acid sequence set forth in SEQ ID NO: 48. In some cases, the antibodies provided herein comprise a heavy chain variable region comprising an amino acid sequence having at least 97% sequence identity to the amino acid sequence set forth in SEQ ID NO: 1, and a light chain variable region comprising an amino acid sequence having at least 97% sequence identity to the amino acid sequence set forth in SEQ ID NO: 48. In some cases, the antibodies provided herein comprise a heavy chain variable region comprising an amino acid sequence having at least 99% sequence identity to the amino acid sequence set forth in SEQ ID NO: 1, and a light chain variable region comprising an amino acid sequence having at least 99% sequence identity to the amino acid sequence set forth in SEQ ID NO: 48. In some cases, the antibodies provided herein comprise a heavy chain variable region comprising an amino acid sequence having 100% sequence identity to the amino acid sequence set forth in SEQ ID NO: 1, and a light chain variable region comprising an amino acid sequence having 100% sequence identity to the amino acid sequence set forth in SEQ ID NO: 48. In some cases, the antibodies provided herein comprise a heavy chain variable region comprising an amino acid sequence having less than or equal to 10, 9, 8, 7, 6, 5, 4, 3, 2, 1 or 0 total substitutions, deletions and / or insertions in the amino acid sequence set forth in SEQ ID NO: 1, and a light chain variable region comprising an amino acid sequence having less than or equal to 10, 9, 8, 7, 6, 5, 4, 3, 2, 1 or 0 total substitutions, deletions and / or insertions in the amino acid sequence set forth in SEQ ID NO: 48.In some cases, the antibodies provided herein comprise a heavy chain variable region comprising an amino acid sequence having less than or equal to 10 total substitutions, deletions and / or insertions in the amino acid sequence set forth in SEQ ID NO: 1, and a light chain variable region comprising an amino acid sequence having less than or equal to 10 total substitutions, deletions and / or insertions in the amino acid sequence set forth in SEQ ID NO: 48. In some cases, the antibodies provided herein comprise a heavy chain variable region comprising an amino acid sequence having less than or equal to 7 total substitutions, deletions and / or insertions in the amino acid sequence set forth in SEQ ID NO: 1, and a light chain variable region comprising an amino acid sequence having less than or equal to 7 total substitutions, deletions and / or insertions in the amino acid sequence set forth in SEQ ID NO: 48. In some cases, the antibodies provided herein comprise a heavy chain variable region comprising an amino acid sequence having less than or equal to 5 total substitutions, deletions and / or insertions in the amino acid sequence set forth in SEQ ID NO: 1, and a light chain variable region comprising an amino acid sequence having less than or equal to 5 total substitutions, deletions and / or insertions in the amino acid sequence set forth in SEQ ID NO: 48. In some cases, the antibodies provided herein comprise a heavy chain variable region comprising an amino acid sequence having less than or equal to 3 total substitutions, deletions and / or insertions in the amino acid sequence set forth in SEQ ID NO: 1, and a light chain variable region comprising an amino acid sequence having less than or equal to 3 total substitutions, deletions and / or insertions in the amino acid sequence set forth in SEQ ID NO: 48. In some cases, the antibodies provided herein comprise a heavy chain variable region comprising an amino acid sequence having less than or equal to 2 total substitutions, deletions and / or insertions in the amino acid sequence set forth in SEQ ID NO: 1, and a light chain variable region comprising an amino acid sequence having less than or equal to 2 total substitutions, deletions and / or insertions in the amino acid sequence set forth in SEQ ID NO: 48. In some cases, the antibodies provided herein comprise a heavy chain variable region comprising an amino acid sequence having less than or equal to 1 total substitution, deletion and / or insertion in the amino acid sequence set forth in SEQ ID NO: 1, and a light chain variable region comprising an amino acid sequence having less than or equal to 1 total substitution, deletion and / or insertion in the amino acid sequence set forth in SEQ ID NO: 48.

[0235] In some cases, the antibodies provided herein comprise a heavy chain variable region comprising an amino acid sequence having at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence set forth in SEQ ID NO: 1, and a light chain variable region comprising an amino acid sequence having at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence set forth in SEQ ID NO: 49. In some cases, the antibodies provided herein comprise a heavy chain variable region comprising an amino acid sequence having at least 95% sequence identity to the amino acid sequence set forth in SEQ ID NO: 1, and a light chain variable region comprising an amino acid sequence having at least 95% sequence identity to the amino acid sequence set forth in SEQ ID NO: 49. In some cases, the antibodies provided herein comprise a heavy chain variable region comprising an amino acid sequence having at least 97% sequence identity to the amino acid sequence set forth in SEQ ID NO: 1, and a light chain variable region comprising an amino acid sequence having at least 97% sequence identity to the amino acid sequence set forth in SEQ ID NO: 49. In some cases, the antibodies provided herein comprise a heavy chain variable region comprising an amino acid sequence having at least 99% sequence identity to the amino acid sequence set forth in SEQ ID NO: 1, and a light chain variable region comprising an amino acid sequence having at least 99% sequence identity to the amino acid sequence set forth in SEQ ID NO: 49. In some cases, the antibodies provided herein comprise a heavy chain variable region comprising an amino acid sequence having 100% sequence identity to the amino acid sequence set forth in SEQ ID NO: 1, and a light chain variable region comprising an amino acid sequence having 100% sequence identity to the amino acid sequence set forth in SEQ ID NO: 49. In some cases, the antibodies provided herein comprise a heavy chain variable region comprising an amino acid sequence having less than or equal to 10, 9, 8, 7, 6, 5, 4, 3, 2, 1 or 0 total substitutions, deletions and / or insertions in the amino acid sequence set forth in SEQ ID NO: 1, and a light chain variable region comprising an amino acid sequence having less than or equal to 10, 9, 8, 7, 6, 5, 4, 3, 2, 1 or 0 total substitutions, deletions and / or insertions in the amino acid sequence set forth in SEQ ID NO: 49.In some cases, the antibodies provided herein comprise a heavy chain variable region comprising an amino acid sequence having less than or equal to 10 total substitutions, deletions and / or insertions in the amino acid sequence set forth in SEQ ID NO: 1, and a light chain variable region comprising an amino acid sequence having less than or equal to 10 total substitutions, deletions and / or insertions in the amino acid sequence set forth in SEQ ID NO: 49. In some cases, the antibodies provided herein comprise a heavy chain variable region comprising an amino acid sequence having less than or equal to 7 total substitutions, deletions and / or insertions in the amino acid sequence set forth in SEQ ID NO: 1, and a light chain variable region comprising an amino acid sequence having less than or equal to 7 total substitutions, deletions and / or insertions in the amino acid sequence set forth in SEQ ID NO: 49. In some cases, the antibodies provided herein comprise a heavy chain variable region comprising an amino acid sequence having less than or equal to 5 total substitutions, deletions and / or insertions in the amino acid sequence set forth in SEQ ID NO: 1, and a light chain variable region comprising an amino acid sequence having less than or equal to 5 total substitutions, deletions and / or insertions in the amino acid sequence set forth in SEQ ID NO: 49. In some cases, the antibodies provided herein comprise a heavy chain variable region comprising an amino acid sequence having less than or equal to 3 total substitutions, deletions and / or insertions in the amino acid sequence set forth in SEQ ID NO: 1, and a light chain variable region comprising an amino acid sequence having less than or equal to 3 total substitutions, deletions and / or insertions in the amino acid sequence set forth in SEQ ID NO: 49. In some cases, the antibodies provided herein comprise a heavy chain variable region comprising an amino acid sequence having less than or equal to 2 total substitutions, deletions and / or insertions in the amino acid sequence set forth in SEQ ID NO: 1, and a light chain variable region comprising an amino acid sequence having less than or equal to 2 total substitutions, deletions and / or insertions in the amino acid sequence set forth in SEQ ID NO: 49. In some cases, the antibodies provided herein comprise a heavy chain variable region comprising an amino acid sequence having less than or equal to 1 total substitution, deletion and / or insertion in the amino acid sequence set forth in SEQ ID NO: 1, and a light chain variable region comprising an amino acid sequence having less than or equal to 1 total substitution, deletion and / or insertion in the amino acid sequence set forth in SEQ ID NO: 49.

[0236] In some cases, the antibodies provided herein comprise a heavy chain variable region comprising an amino acid sequence having at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence set forth in SEQ ID NO: 1, and a light chain variable region comprising an amino acid sequence having at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence set forth in SEQ ID NO: 50. In some cases, the antibodies provided herein comprise a heavy chain variable region comprising an amino acid sequence having at least 95% sequence identity to the amino acid sequence set forth in SEQ ID NO: 1, and a light chain variable region comprising an amino acid sequence having at least 95% sequence identity to the amino acid sequence set forth in SEQ ID NO: 50. In some cases, the antibodies provided herein comprise a heavy chain variable region comprising an amino acid sequence having at least 97% sequence identity to the amino acid sequence set forth in SEQ ID NO: 1, and a light chain variable region comprising an amino acid sequence having at least 97% sequence identity to the amino acid sequence set forth in SEQ ID NO: 50. In some cases, the antibodies provided herein comprise a heavy chain variable region comprising an amino acid sequence having at least 99% sequence identity to the amino acid sequence set forth in SEQ ID NO: 1, and a light chain variable region comprising an amino acid sequence having at least 99% sequence identity to the amino acid sequence set forth in SEQ ID NO: 50. In some cases, the antibodies provided herein comprise a heavy chain variable region comprising an amino acid sequence having 100% sequence identity to the amino acid sequence set forth in SEQ ID NO: 1, and a light chain variable region comprising an amino acid sequence having 100% sequence identity to the amino acid sequence set forth in SEQ ID NO: 50. In some cases, the antibodies provided herein comprise a heavy chain variable region comprising an amino acid sequence having less than or equal to 10, 9, 8, 7, 6, 5, 4, 3, 2, 1 or 0 total substitutions, deletions and / or insertions in the amino acid sequence as shown in SEQ ID NO: 1, and a light chain variable region comprising an amino acid sequence having less than or equal to 10, 9, 8, 7, 6, 5, 4, 3, 2, 1 or 0 total substitutions, deletions and / or insertions in the amino acid sequence as shown in SEQ ID NO: 50.In some cases, the antibodies provided herein comprise a heavy chain variable region comprising an amino acid sequence having less than or equal to 10 total substitutions, deletions and / or insertions in the amino acid sequence set forth in SEQ ID NO: 1, and a light chain variable region comprising an amino acid sequence having less than or equal to 10 total substitutions, deletions and / or insertions in the amino acid sequence set forth in SEQ ID NO: 50. In some cases, the antibodies provided herein comprise a heavy chain variable region comprising an amino acid sequence having less than or equal to 7 total substitutions, deletions and / or insertions in the amino acid sequence set forth in SEQ ID NO: 1, and a light chain variable region comprising an amino acid sequence having less than or equal to 7 total substitutions, deletions and / or insertions in the amino acid sequence set forth in SEQ ID NO: 50. In some cases, the antibodies provided herein comprise a heavy chain variable region comprising an amino acid sequence having less than or equal to 5 total substitutions, deletions and / or insertions in the amino acid sequence set forth in SEQ ID NO: 1, and a light chain variable region comprising an amino acid sequence having less than or equal to 5 total substitutions, deletions and / or insertions in the amino acid sequence set forth in SEQ ID NO: 50. In some cases, the antibodies provided herein comprise a heavy chain variable region comprising an amino acid sequence having less than or equal to 3 total substitutions, deletions and / or insertions in the amino acid sequence set forth in SEQ ID NO: 1, and a light chain variable region comprising an amino acid sequence having less than or equal to 3 total substitutions, deletions and / or insertions in the amino acid sequence set forth in SEQ ID NO: 50. In some cases, the antibodies provided herein comprise a heavy chain variable region comprising an amino acid sequence having less than or equal to 2 total substitutions, deletions and / or insertions in the amino acid sequence set forth in SEQ ID NO: 1, and a light chain variable region comprising an amino acid sequence having less than or equal to 2 total substitutions, deletions and / or insertions in the amino acid sequence set forth in SEQ ID NO: 50. In some cases, the antibodies provided herein comprise a heavy chain variable region comprising an amino acid sequence having less than or equal to 1 total substitution, deletion and / or insertion in the amino acid sequence set forth in SEQ ID NO: 1, and a light chain variable region comprising an amino acid sequence having less than or equal to 1 total substitution, deletion and / or insertion in the amino acid sequence set forth in SEQ ID NO: 50.

[0237] In some cases, the antibodies provided herein comprise a heavy chain variable region comprising an amino acid sequence having at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence set forth in SEQ ID NO: 1, and a light chain variable region comprising an amino acid sequence having at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence set forth in SEQ ID NO: 51. In some cases, the antibodies provided herein comprise a heavy chain variable region comprising an amino acid sequence having at least 95% sequence identity to the amino acid sequence set forth in SEQ ID NO: 1, and a light chain variable region comprising an amino acid sequence having at least 95% sequence identity to the amino acid sequence set forth in SEQ ID NO: 51. In some cases, the antibodies provided herein comprise a heavy chain variable region comprising an amino acid sequence having at least 97% sequence identity to the amino acid sequence set forth in SEQ ID NO: 1, and a light chain variable region comprising an amino acid sequence having at least 97% sequence identity to the amino acid sequence set forth in SEQ ID NO: 51. In some cases, the antibodies provided herein comprise a heavy chain variable region comprising an amino acid sequence having at least 99% sequence identity to the amino acid sequence set forth in SEQ ID NO: 1, and a light chain variable region comprising an amino acid sequence having at least 99% sequence identity to the amino acid sequence set forth in SEQ ID NO: 51. In some cases, the antibodies provided herein comprise a heavy chain variable region comprising an amino acid sequence having 100% sequence identity to the amino acid sequence set forth in SEQ ID NO: 1, and a light chain variable region comprising an amino acid sequence having 100% sequence identity to the amino acid sequence set forth in SEQ ID NO: 51. In some cases, the antibodies provided herein comprise a heavy chain variable region comprising an amino acid sequence having less than or equal to 10, 9, 8, 7, 6, 5, 4, 3, 2, 1 or 0 total substitutions, deletions and / or insertions in the amino acid sequence as shown in SEQ ID NO: 1, and a light chain variable region comprising an amino acid sequence having less than or equal to 10, 9, 8, 7, 6, 5, 4, 3, 2, 1 or 0 total substitutions, deletions and / or insertions in the amino acid sequence as shown in SEQ ID NO:51.In some cases, the antibodies provided herein comprise a heavy chain variable region comprising an amino acid sequence having less than or equal to 10 total substitutions, deletions and / or insertions in the amino acid sequence set forth in SEQ ID NO: 1, and a light chain variable region comprising an amino acid sequence having less than or equal to 10 total substitutions, deletions and / or insertions in the amino acid sequence set forth in SEQ ID NO: 51. In some cases, the antibodies provided herein comprise a heavy chain variable region comprising an amino acid sequence having less than or equal to 7 total substitutions, deletions and / or insertions in the amino acid sequence set forth in SEQ ID NO: 1, and a light chain variable region comprising an amino acid sequence having less than or equal to 7 total substitutions, deletions and / or insertions in the amino acid sequence set forth in SEQ ID NO: 51. In some cases, the antibodies provided herein comprise a heavy chain variable region comprising an amino acid sequence having less than or equal to 5 total substitutions, deletions and / or insertions in the amino acid sequence set forth in SEQ ID NO: 1, and a light chain variable region comprising an amino acid sequence having less than or equal to 5 total substitutions, deletions and / or insertions in the amino acid sequence set forth in SEQ ID NO: 51. In some cases, the antibodies provided herein comprise a heavy chain variable region comprising an amino acid sequence having less than or equal to 3 total substitutions, deletions and / or insertions in the amino acid sequence set forth in SEQ ID NO: 1, and a light chain variable region comprising an amino acid sequence having less than or equal to 3 total substitutions, deletions and / or insertions in the amino acid sequence set forth in SEQ ID NO: 51. In some cases, the antibodies provided herein comprise a heavy chain variable region comprising an amino acid sequence having less than or equal to 2 total substitutions, deletions and / or insertions in the amino acid sequence set forth in SEQ ID NO: 1, and a light chain variable region comprising an amino acid sequence having less than or equal to 2 total substitutions, deletions and / or insertions in the amino acid sequence set forth in SEQ ID NO: 51. In some cases, the antibodies provided herein comprise a heavy chain variable region comprising an amino acid sequence having less than or equal to 1 total substitution, deletion and / or insertion in the amino acid sequence set forth in SEQ ID NO: 1, and a light chain variable region comprising an amino acid sequence having less than or equal to 1 total substitution, deletion and / or insertion in the amino acid sequence set forth in SEQ ID NO: 51.

[0238] In some cases, the antibodies provided herein comprise a heavy chain variable region comprising an amino acid sequence having at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence set forth in SEQ ID NO: 1, and a light chain variable region comprising an amino acid sequence having at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence set forth in SEQ ID NO: 52. In some cases, the antibodies provided herein comprise a heavy chain variable region comprising an amino acid sequence having at least 95% sequence identity to the amino acid sequence set forth in SEQ ID NO: 1, and a light chain variable region comprising an amino acid sequence having at least 95% sequence identity to the amino acid sequence set forth in SEQ ID NO: 52. In some cases, the antibodies provided herein comprise a heavy chain variable region comprising an amino acid sequence having at least 97% sequence identity to the amino acid sequence set forth in SEQ ID NO: 1, and a light chain variable region comprising an amino acid sequence having at least 97% sequence identity to the amino acid sequence set forth in SEQ ID NO: 52. In some cases, the antibodies provided herein comprise a heavy chain variable region comprising an amino acid sequence having at least 99% sequence identity to the amino acid sequence set forth in SEQ ID NO: 1, and a light chain variable region comprising an amino acid sequence having at least 99% sequence identity to the amino acid sequence set forth in SEQ ID NO: 52. In some cases, the antibodies provided herein comprise a heavy chain variable region comprising an amino acid sequence having 100% sequence identity to the amino acid sequence set forth in SEQ ID NO: 1, and a light chain variable region comprising an amino acid sequence having 100% sequence identity to the amino acid sequence set forth in SEQ ID NO: 52. In some cases, the antibodies provided herein comprise a heavy chain variable region comprising an amino acid sequence having less than or equal to 10, 9, 8, 7, 6, 5, 4, 3, 2, 1 or 0 total substitutions, deletions and / or insertions in the amino acid sequence as shown in SEQ ID NO: 1, and a light chain variable region comprising an amino acid sequence having less than or equal to 10, 9, 8, 7, 6, 5, 4, 3, 2, 1 or 0 total substitutions, deletions and / or insertions in the amino acid sequence as shown in SEQ ID NO: 52.In some cases, the antibodies provided herein comprise a heavy chain variable region comprising an amino acid sequence having less than or equal to 10 total substitutions, deletions and / or insertions in the amino acid sequence set forth in SEQ ID NO: 1, and a light chain variable region comprising an amino acid sequence having less than or equal to 10 total substitutions, deletions and / or insertions in the amino acid sequence set forth in SEQ ID NO: 52. In some cases, the antibodies provided herein comprise a heavy chain variable region comprising an amino acid sequence having less than or equal to 7 total substitutions, deletions and / or insertions in the amino acid sequence set forth in SEQ ID NO: 1, and a light chain variable region comprising an amino acid sequence having less than or equal to 7 total substitutions, deletions and / or insertions in the amino acid sequence set forth in SEQ ID NO: 52. In some cases, the antibodies provided herein comprise a heavy chain variable region comprising an amino acid sequence having less than or equal to 5 total substitutions, deletions and / or insertions in the amino acid sequence set forth in SEQ ID NO: 1, and a light chain variable region comprising an amino acid sequence having less than or equal to 5 total substitutions, deletions and / or insertions in the amino acid sequence set forth in SEQ ID NO: 52. In some cases, the antibodies provided herein comprise a heavy chain variable region comprising an amino acid sequence having less than or equal to 3 total substitutions, deletions and / or insertions in the amino acid sequence set forth in SEQ ID NO: 1, and a light chain variable region comprising an amino acid sequence having less than or equal to 3 total substitutions, deletions and / or insertions in the amino acid sequence set forth in SEQ ID NO: 52. In some cases, the antibodies provided herein comprise a heavy chain variable region comprising an amino acid sequence having less than or equal to 2 total substitutions, deletions and / or insertions in the amino acid sequence set forth in SEQ ID NO: 1, and a light chain variable region comprising an amino acid sequence having less than or equal to 2 total substitutions, deletions and / or insertions in the amino acid sequence set forth in SEQ ID NO: 52. In some cases, the antibodies provided herein comprise a heavy chain variable region comprising an amino acid sequence having less than or equal to 1 total substitution, deletion and / or insertion in the amino acid sequence set forth in SEQ ID NO: 1, and a light chain variable region comprising an amino acid sequence having less than or equal to 1 total substitution, deletion and / or insertion in the amino acid sequence set forth in SEQ ID NO: 52.

[0239] In some cases, the antibodies provided herein comprise a heavy chain variable region comprising an amino acid sequence having at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence set forth in SEQ ID NO: 1, and a light chain variable region comprising an amino acid sequence having at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence set forth in SEQ ID NO: 65. In some cases, the antibodies provided herein comprise a heavy chain variable region comprising an amino acid sequence having at least 95% sequence identity to the amino acid sequence set forth in SEQ ID NO: 1, and a light chain variable region comprising an amino acid sequence having at least 95% sequence identity to the amino acid sequence set forth in SEQ ID NO: 65. In some cases, the antibodies provided herein comprise a heavy chain variable region comprising an amino acid sequence having at least 97% sequence identity to the amino acid sequence set forth in SEQ ID NO: 1, and a light chain variable region comprising an amino acid sequence having at least 97% sequence identity to the amino acid sequence set forth in SEQ ID NO: 65. In some cases, the antibodies provided herein comprise a heavy chain variable region comprising an amino acid sequence having at least 99% sequence identity to the amino acid sequence set forth in SEQ ID NO: 1, and a light chain variable region comprising an amino acid sequence having at least 99% sequence identity to the amino acid sequence set forth in SEQ ID NO: 65. In some cases, the antibodies provided herein comprise a heavy chain variable region comprising an amino acid sequence having 100% sequence identity to the amino acid sequence set forth in SEQ ID NO: 1, and a light chain variable region comprising an amino acid sequence having 100% sequence identity to the amino acid sequence set forth in SEQ ID NO: 65. In some cases, the antibodies provided herein comprise a heavy chain variable region comprising an amino acid sequence having less than or equal to 10, 9, 8, 7, 6, 5, 4, 3, 2, 1 or 0 total substitutions, deletions and / or insertions in the amino acid sequence set forth in SEQ ID NO: 1, and a light chain variable region comprising an amino acid sequence having less than or equal to 10, 9, 8, 7, 6, 5, 4, 3, 2, 1 or 0 total substitutions, deletions and / or insertions in the amino acid sequence set forth in SEQ ID NO: 65.In some cases, the antibodies provided herein comprise a heavy chain variable region comprising an amino acid sequence having less than or equal to 10 total substitutions, deletions and / or insertions in the amino acid sequence set forth in SEQ ID NO: 1, and a light chain variable region comprising an amino acid sequence having less than or equal to 10 total substitutions, deletions and / or insertions in the amino acid sequence set forth in SEQ ID NO: 65. In some cases, the antibodies provided herein comprise a heavy chain variable region comprising an amino acid sequence having less than or equal to 7 total substitutions, deletions and / or insertions in the amino acid sequence set forth in SEQ ID NO: 1, and a light chain variable region comprising an amino acid sequence having less than or equal to 7 total substitutions, deletions and / or insertions in the amino acid sequence set forth in SEQ ID NO: 65. In some cases, the antibodies provided herein comprise a heavy chain variable region comprising an amino acid sequence having less than or equal to 5 total substitutions, deletions and / or insertions in the amino acid sequence set forth in SEQ ID NO: 1, and a light chain variable region comprising an amino acid sequence having less than or equal to 5 total substitutions, deletions and / or insertions in the amino acid sequence set forth in SEQ ID NO: 65. In some cases, the antibodies provided herein comprise a heavy chain variable region comprising an amino acid sequence having less than or equal to 3 total substitutions, deletions and / or insertions in the amino acid sequence set forth in SEQ ID NO: 1, and a light chain variable region comprising an amino acid sequence having less than or equal to 3 total substitutions, deletions and / or insertions in the amino acid sequence set forth in SEQ ID NO: 65. In some cases, the antibodies provided herein comprise a heavy chain variable region comprising an amino acid sequence having less than or equal to 2 total substitutions, deletions and / or insertions in the amino acid sequence set forth in SEQ ID NO: 1, and a light chain variable region comprising an amino acid sequence having less than or equal to 2 total substitutions, deletions and / or insertions in the amino acid sequence set forth in SEQ ID NO: 65. In some cases, the antibodies provided herein comprise a heavy chain variable region comprising an amino acid sequence having less than or equal to 1 total substitution, deletion and / or insertion in the amino acid sequence set forth in SEQ ID NO: 1, and a light chain variable region comprising an amino acid sequence having less than or equal to 1 total substitution, deletion and / or insertion in the amino acid sequence set forth in SEQ ID NO: 65.

[0240] In some cases, the antibodies provided herein comprise a heavy chain variable region comprising an amino acid sequence having at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence set forth in SEQ ID NO: 1, and a light chain variable region comprising an amino acid sequence having at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence set forth in SEQ ID NO: 66. In some cases, the antibodies provided herein comprise a heavy chain variable region comprising an amino acid sequence having at least 95% sequence identity to the amino acid sequence set forth in SEQ ID NO: 1, and a light chain variable region comprising an amino acid sequence having at least 95% sequence identity to the amino acid sequence set forth in SEQ ID NO: 66. In some cases, the antibodies provided herein comprise a heavy chain variable region comprising an amino acid sequence having at least 97% sequence identity to the amino acid sequence set forth in SEQ ID NO: 1, and a light chain variable region comprising an amino acid sequence having at least 97% sequence identity to the amino acid sequence set forth in SEQ ID NO: 66. In some cases, the antibodies provided herein comprise a heavy chain variable region comprising an amino acid sequence having at least 99% sequence identity to the amino acid sequence set forth in SEQ ID NO: 1, and a light chain variable region comprising an amino acid sequence having at least 99% sequence identity to the amino acid sequence set forth in SEQ ID NO: 66. In some cases, the antibodies provided herein comprise a heavy chain variable region comprising an amino acid sequence having 100% sequence identity to the amino acid sequence set forth in SEQ ID NO: 1, and a light chain variable region comprising an amino acid sequence having 100% sequence identity to the amino acid sequence set forth in SEQ ID NO: 66. In some cases, the antibodies provided herein comprise a heavy chain variable region comprising an amino acid sequence having less than or equal to 10, 9, 8, 7, 6, 5, 4, 3, 2, 1 or 0 total substitutions, deletions and / or insertions in the amino acid sequence set forth in SEQ ID NO: 1, and a light chain variable region comprising an amino acid sequence having less than or equal to 10, 9, 8, 7, 6, 5, 4, 3, 2, 1 or 0 total substitutions, deletions and / or insertions in the amino acid sequence set forth in SEQ ID NO: 66.In some cases, the antibodies provided herein comprise a heavy chain variable region comprising an amino acid sequence having less than or equal to 10 total substitutions, deletions and / or insertions in the amino acid sequence set forth in SEQ ID NO: 1, and a light chain variable region comprising an amino acid sequence having less than or equal to 10 total substitutions, deletions and / or insertions in the amino acid sequence set forth in SEQ ID NO: 66. In some cases, the antibodies provided herein comprise a heavy chain variable region comprising an amino acid sequence having less than or equal to 7 total substitutions, deletions and / or insertions in the amino acid sequence set forth in SEQ ID NO: 1, and a light chain variable region comprising an amino acid sequence having less than or equal to 7 total substitutions, deletions and / or insertions in the amino acid sequence set forth in SEQ ID NO: 66. In some cases, the antibodies provided herein comprise a heavy chain variable region comprising an amino acid sequence having less than or equal to 5 total substitutions, deletions and / or insertions in the amino acid sequence set forth in SEQ ID NO: 1, and a light chain variable region comprising an amino acid sequence having less than or equal to 5 total substitutions, deletions and / or insertions in the amino acid sequence set forth in SEQ ID NO: 66. In some cases, the antibodies provided herein comprise a heavy chain variable region comprising an amino acid sequence having less than or equal to 3 total substitutions, deletions and / or insertions in the amino acid sequence set forth in SEQ ID NO: 1, and a light chain variable region comprising an amino acid sequence having less than or equal to 3 total substitutions, deletions and / or insertions in the amino acid sequence set forth in SEQ ID NO: 66. In some cases, the antibodies provided herein comprise a heavy chain variable region comprising an amino acid sequence having less than or equal to 2 total substitutions, deletions and / or insertions in the amino acid sequence set forth in SEQ ID NO: 1, and a light chain variable region comprising an amino acid sequence having less than or equal to 2 total substitutions, deletions and / or insertions in the amino acid sequence set forth in SEQ ID NO: 66. In some cases, the antibodies provided herein comprise a heavy chain variable region comprising an amino acid sequence having less than or equal to 1 total substitution, deletion and / or insertion in the amino acid sequence set forth in SEQ ID NO: 1, and a light chain variable region comprising an amino acid sequence having less than or equal to 1 total substitution, deletion and / or insertion in the amino acid sequence set forth in SEQ ID NO: 66.

[0241] In some cases, the antibodies provided herein comprise a heavy chain variable region comprising an amino acid sequence having at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence set forth in SEQ ID NO: 42, and a light chain variable region comprising an amino acid sequence having at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence set forth in SEQ ID NO: 2. In some cases, the antibodies provided herein comprise a heavy chain variable region comprising an amino acid sequence having at least 95% sequence identity to the amino acid sequence set forth in SEQ ID NO: 42, and a light chain variable region comprising an amino acid sequence having at least 95% sequence identity to the amino acid sequence set forth in SEQ ID NO: 2. In some cases, the antibodies provided herein comprise a heavy chain variable region comprising an amino acid sequence having at least 97% sequence identity to the amino acid sequence set forth in SEQ ID NO: 42, and a light chain variable region comprising an amino acid sequence having at least 97% sequence identity to the amino acid sequence set forth in SEQ ID NO: 2. In some cases, the antibodies provided herein comprise a heavy chain variable region comprising an amino acid sequence having at least 99% sequence identity to the amino acid sequence set forth in SEQ ID NO: 42, and a light chain variable region comprising an amino acid sequence having at least 99% sequence identity to the amino acid sequence set forth in SEQ ID NO: 2. In some cases, the antibodies provided herein comprise a heavy chain variable region comprising an amino acid sequence having 100% sequence identity to the amino acid sequence set forth in SEQ ID NO: 42, and a light chain variable region comprising an amino acid sequence having 100% sequence identity to the amino acid sequence set forth in SEQ ID NO: 2. In some cases, the antibodies provided herein comprise a heavy chain variable region comprising an amino acid sequence having less than or equal to 10, 9, 8, 7, 6, 5, 4, 3, 2, 1 or 0 total substitutions, deletions and / or insertions in the amino acid sequence as shown in SEQ ID NO:42, and a light chain variable region comprising an amino acid sequence having less than or equal to 10, 9, 8, 7, 6, 5, 4, 3, 2, 1 or 0 total substitutions, deletions and / or insertions in the amino acid sequence as shown in SEQ ID NO:2.In some cases, the antibodies provided herein comprise a heavy chain variable region comprising an amino acid sequence having less than or equal to 10 total substitutions, deletions and / or insertions in the amino acid sequence set forth in SEQ ID NO: 42, and a light chain variable region comprising an amino acid sequence having less than or equal to 10 total substitutions, deletions and / or insertions in the amino acid sequence set forth in SEQ ID NO: 2. In some cases, the antibodies provided herein comprise a heavy chain variable region comprising an amino acid sequence having less than or equal to 7 total substitutions, deletions and / or insertions in the amino acid sequence set forth in SEQ ID NO: 42, and a light chain variable region comprising an amino acid sequence having less than or equal to 7 total substitutions, deletions and / or insertions in the amino acid sequence set forth in SEQ ID NO: 2. In some cases, the antibodies provided herein comprise a heavy chain variable region comprising an amino acid sequence having less than or equal to 5 total substitutions, deletions and / or insertions in the amino acid sequence set forth in SEQ ID NO: 42, and a light chain variable region comprising an amino acid sequence having less than or equal to 5 total substitutions, deletions and / or insertions in the amino acid sequence set forth in SEQ ID NO: 2. In some cases, the antibodies provided herein comprise a heavy chain variable region comprising an amino acid sequence having less than or equal to 3 total substitutions, deletions and / or insertions in the amino acid sequence set forth in SEQ ID NO: 42, and a light chain variable region comprising an amino acid sequence having less than or equal to 3 total substitutions, deletions and / or insertions in the amino acid sequence set forth in SEQ ID NO: 2. In some cases, the antibodies provided herein comprise a heavy chain variable region comprising an amino acid sequence having less than or equal to 2 total substitutions, deletions and / or insertions in the amino acid sequence set forth in SEQ ID NO: 42, and a light chain variable region comprising an amino acid sequence having less than or equal to 2 total substitutions, deletions and / or insertions in the amino acid sequence set forth in SEQ ID NO: 2. In some cases, the antibodies provided herein comprise a heavy chain variable region comprising an amino acid sequence having less than or equal to 1 total substitution, deletion and / or insertion in the amino acid sequence set forth in SEQ ID NO: 42, and a light chain variable region comprising an amino acid sequence having less than or equal to 1 total substitution, deletion and / or insertion in the amino acid sequence set forth in SEQ ID NO: 2.

[0242] In some cases, the antibodies provided herein comprise a heavy chain variable region comprising an amino acid sequence having at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence set forth in SEQ ID NO: 42, and a light chain variable region comprising an amino acid sequence having at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence set forth in SEQ ID NO: 48. In some cases, the antibodies provided herein comprise a heavy chain variable region comprising an amino acid sequence having at least 95% sequence identity to the amino acid sequence set forth in SEQ ID NO: 42, and a light chain variable region comprising an amino acid sequence having at least 95% sequence identity to the amino acid sequence set forth in SEQ ID NO: 48. In some cases, the antibodies provided herein comprise a heavy chain variable region comprising an amino acid sequence having at least 97% sequence identity to the amino acid sequence set forth in SEQ ID NO: 42, and a light chain variable region comprising an amino acid sequence having at least 97% sequence identity to the amino acid sequence set forth in SEQ ID NO: 48. In some cases, the antibodies provided herein comprise a heavy chain variable region comprising an amino acid sequence having at least 99% sequence identity to the amino acid sequence set forth in SEQ ID NO: 42, and a light chain variable region comprising an amino acid sequence having at least 99% sequence identity to the amino acid sequence set forth in SEQ ID NO: 48. In some cases, the antibodies provided herein comprise a heavy chain variable region comprising an amino acid sequence having 100% sequence identity to the amino acid sequence set forth in SEQ ID NO: 42, and a light chain variable region comprising an amino acid sequence having 100% sequence identity to the amino acid sequence set forth in SEQ ID NO: 48. In some cases, the antibodies provided herein comprise a heavy chain variable region comprising an amino acid sequence having less than or equal to 10, 9, 8, 7, 6, 5, 4, 3, 2, 1 or 0 total substitutions, deletions and / or insertions in the amino acid sequence as shown in SEQ ID NO:42, and a light chain variable region comprising an amino acid sequence having less ...

Claims

1. An antibody or antigen-binding fragment thereof that specifically binds to CD200R, comprising (a) a heavy chain, wherein the heavy chain comprises a heavy chain variable region (HCVR), wherein the heavy chain variable region comprises at least one heavy chain complementary determining region (CDR) as shown in any one of SEQ ID NO: 3, 4, 41, 5, 11, 12, 13, 19, 20, 21, 27, 28, 29, 35, 36, 37, 69, 70 or 92 with 0 to 3 amino acid modifications; and / or (b) a light chain, wherein the light chain comprises a light chain variable region (LCVR), wherein the light chain variable region comprises at least one light chain complementary determining region (CDR) as shown in any one of SEQ ID NO: 6, 7, 8, 14, 15, 16, 22, 23, 24, 30, 31, 32, 38, 39, 40, 67, 68 or 87 to 91 with 0 to 3 amino acid modifications.

2. An antibody or antigen-binding fragment thereof that specifically binds to CD200R, the antibody or antigen-binding fragment thereof comprising a heavy chain and a light chain, wherein the heavy chain comprises a heavy chain variable region comprising a heavy chain complementary determining region 1 (CDRH1), CDRH2 and CDRH3, and wherein CDRH1, CDRH2 and CDRH3 comprise: a) the sequences shown as SEQ ID NOs: 3, 41 and 70, respectively, each having 0 to 3 amino acid modifications, such as 0, 1, 2 or 3 modifications; b) the sequences shown as SEQ ID NOs: 3, 41 and 69, respectively, each having 0 to 3 amino acid modifications, such as 0, 1, 2 or 3 modifications; c) the sequences shown as SEQ ID NOs: 3, 41 and 5, respectively, each having 0 to 3 amino acid modifications, such as 0, 1, 2 or 3 modifications; d) the sequences shown as SEQ ID NOs: 3, 4 and 5, respectively, each having 0 to 3 amino acid modifications, such as 0, 1, 2 or 3 modifications; e) the sequences shown as SEQ ID NOs: 11, 12 and 13, respectively, each having 0 to 3 amino acid modifications, such as 0, 1, 2 or 3 modifications; f) the sequences shown as SEQ ID NOs: 19, 20 and 21, respectively, each having 0 to 3 amino acid modifications, such as 0, 1, 2 or 3 modifications; g) the sequences shown as SEQ ID NOs: 27, 28 and 29, respectively, each having 0 to 3 amino acid modifications, such as 0, 1, 2 or 3 modifications; h) the sequences shown in SEQ ID NOs: 35, 36 and 37, respectively, each having 0 to 3 amino acid modifications, such as 0, 1, 2 or 3 modifications; or i) SEQ ID NO: 92, 41 and 69.

3. An antibody or antigen-binding fragment thereof, comprising a heavy chain and a light chain, wherein the light chain comprises a light chain variable region comprising light chain complementary determining region 1 (CDRL1), CDRL2 and CDRL3, and wherein CDRL1, CDRL2 and CDRL3 comprise: a) the sequences shown as SEQ ID NOs: 6, 67 and 8, respectively, each having 0 to 3 amino acid modifications, such as 0, 1, 2 or 3 modifications; b) the sequences shown as SEQ ID NOs: 6, 7 and 8, respectively, each having 0 to 3 amino acid modifications, such as 0, 1, 2 or 3 modifications; c) the sequences shown as SEQ ID NOs: 14, 15 and 16, respectively, each having 0 to 3 amino acid modifications, such as 0, 1, 2 or 3 modifications; d) the sequences shown as SEQ ID NOs: 22, 23 and 24, respectively, each having 0 to 3 amino acid modifications, such as 0, 1, 2 or 3 modifications; e) the sequences shown as SEQ ID NOs: 30, 31 and 32, respectively, each having 0 to 3 amino acid modifications, such as 0, 1, 2 or 3 modifications; f) the sequences shown in SEQ ID NOs: 38, 39 and 40, respectively, each having 0 to 3 amino acid modifications, such as 0, 1, 2 or 3 modifications; or g) the sequences shown as SEQ ID NOs: 6, 68 and 8, respectively, each having 0 to 3 amino acid modifications, such as 0, 1, 2 or 3 modifications.

4. An antibody or antigen-binding fragment thereof that specifically binds to CD200R, the antibody or antigen-binding fragment thereof comprising: a) a heavy chain comprising a heavy chain variable region (HCVR) and a light chain comprising a light chain variable region (LCVR), wherein the HCVR comprises at least one heavy chain CDR as shown in any one of SEQ ID NOs: 3, 4, 41, 5, 69 or 70 having 0 to 3 amino acid modifications, wherein the LCVR comprises at least one light chain CDR as shown in any one of SEQ ID NOs: 6, 67 or 8 having 0 to 3 amino acid modifications; b) a heavy chain comprising a heavy chain variable region (HCVR) and a light chain comprising a light chain variable region (LCVR), wherein the HCVR comprises at least one heavy chain CDR as shown in any one of SEQ ID NOs: 3, 4, 41, 5, 69 or 70 having 0 to 3 amino acid modifications, wherein the LCVR comprises at least one light chain CDR as shown in any one of SEQ ID NOs: 6, 7 or 8 having 0 to 3 amino acid modifications; c) a heavy chain comprising a heavy chain variable region (HCVR) and a light chain comprising a light chain variable region (LCVR), wherein the HCVR comprises at least one heavy chain CDR as shown in any one of SEQ ID NOs: 3, 4, 41, 5, 69 or 70 having 0 to 3 amino acid modifications, wherein the LCVR comprises at least one light chain CDR as shown in any one of SEQ ID NOs: 6, 68 or 8 having 0 to 3 amino acid modifications; d) a heavy chain comprising a heavy chain variable region (HCVR) and a light chain comprising a light chain variable region (LCVR), wherein the HCVR comprises at least one heavy chain CDR as shown in any one of SEQ ID NOs: 3, 41 or 70 having 0 to 3 amino acid modifications, wherein the LCVR comprises at least one light chain CDR as shown in any one of SEQ ID NOs: 6, 67 or 8 having 0 to 3 amino acid modifications; e) a heavy chain comprising a heavy chain variable region (HCVR) and a light chain comprising a light chain variable region (LCVR), wherein the HCVR comprises at least one heavy chain CDR as shown in any one of SEQ ID NOs: 3, 41 or 69 having 0 to 3 amino acid modifications, wherein the LCVR comprises at least one light chain CDR as shown in any one of SEQ ID NOs: 6, 67 or 8 having 0 to 3 amino acid modifications; f) a heavy chain comprising a heavy chain variable region (HCVR) and a light chain comprising a light chain variable region (LCVR), wherein the HCVR comprises at least one heavy chain CDR as shown in any one of SEQ ID NOs: 11, 12 or 13 having 0 to 3 amino acid modifications, wherein the LCVR comprises at least one light chain CDR as shown in any one of SEQ ID NOs: 14, 15 or 16 having 0 to 3 amino acid modifications; g) a heavy chain comprising a heavy chain variable region (HCVR) and a light chain comprising a light chain variable region (LCVR), wherein the HCVR comprises at least one heavy chain CDR as shown in any one of SEQ ID NOs: 19, 20 or 21 having 0 to 3 amino acid modifications, wherein the LCVR comprises at least one light chain CDR as shown in any one of SEQ ID NOs: 22, 23 or 24 having 0 to 3 amino acid modifications; h) a heavy chain comprising a heavy chain variable region (HCVR) and a light chain comprising a light chain variable region (LCVR), wherein the HCVR comprises at least one heavy chain CDR as shown in any one of SEQ ID NOs: 27, 28 or 29 having 0 to 3 amino acid modifications, wherein the LCVR comprises at least one light chain CDR as shown in any one of SEQ ID NOs: 30, 31 or 32 having 0 to 3 amino acid modifications; or i) a heavy chain comprising a heavy chain variable region (HCVR) and a light chain comprising a light chain variable region (LCVR), wherein the HCVR comprises at least one heavy chain CDR as shown in any one of SEQ ID NOs: 35, 36 or 37 having 0 to 3 amino acid modifications, and wherein the LCVR comprises at least one light chain CDR as shown in any one of SEQ ID NOs: 38, 39 or 40 having 0 to 3 amino acid modifications.

5. An antibody or antigen-binding fragment thereof, comprising a heavy chain and a light chain, wherein: a) the heavy chain comprises a heavy chain variable region (HCVR), comprising a heavy chain complementary determining region 1 (CDRH1), CDRH2 and CDRH3, wherein CDRH1, CDRH2 and CDRH3 comprise the sequences shown in SEQ ID NOs: 3, 41 and 70, respectively, each having 0 to 3 amino acid modifications, such as 0, 1, 2 or 3 modifications; and the light chain comprises a light chain variable region (LCVR), comprising a light chain complementary determining region 1 (CDRL1), CDRL2 and CDRL3, wherein CDRL1, CDRL2 and CDRL3 comprise the sequences shown in SEQ ID NOs: 6, 67 and 8, respectively, each having 0 to 3 amino acid modifications, such as 0, 1, 2 or 3 modifications; b) the heavy chain comprises a heavy chain variable region (HCVR), comprising a heavy chain complementary determining region 1 (CDRH1), CDRH2 and CDRH3, wherein CDRH1, CDRH2 and CDRH3 comprise the sequences shown in SEQ ID NOs: 3, 41 and 5, respectively, each having 0 to 3 amino acid modifications, such as 0, 1, 2 or 3 modifications; and the light chain comprises a light chain variable region (LCVR), comprising a light chain complementary determining region 1 (CDRL1), CDRL2 and CDRL3, wherein CDRL1, CDRL2 and CDRL3 comprise the sequences shown in SEQ ID NOs: 6, 67 and 8, respectively, each having 0 to 3 amino acid modifications, such as 0, 1, 2 or 3 modifications; c) the heavy chain comprises a heavy chain variable region (HCVR), comprising a heavy chain complementary determining region 1 (CDRH1), CDRH2 and CDRH3, wherein CDRH1, CDRH2 and CDRH3 comprise the sequences shown in SEQ ID NOs: 3, 4 and 5, respectively, each having 0 to 3 amino acid modifications, such as 0, 1, 2 or 3 modifications; and the light chain comprises a light chain variable region (LCVR), comprising a light chain complementary determining region 1 (CDRL1), CDRL2 and CDRL3, wherein CDRL1, CDRL2 and CDRL3 comprise the sequences shown in SEQ ID NOs: 6, 7 and 8, respectively, each having 0 to 3 amino acid modifications, such as 0, 1, 2 or 3 modifications; d) the heavy chain comprises a heavy chain variable region (HCVR), comprising heavy chain CDRH1, CDRH2 and CDRH3, and wherein CDRH1, CDRH2 and CDRH3 comprise the sequences shown in SEQ ID NOs: 3, 41 and 5, respectively, each having 0 to 3 amino acid modifications, such as 0, 1, 2 or 3 modifications; and the light chain comprises a light chain variable region (LCVR), comprising CDRL1, CDRL2 and CDRL3, and wherein CDRL1, CDRL2 and CDRL3 comprise the sequences shown in SEQ ID NOs: 6, 7 and 8, respectively, each having 0 to 3 amino acid modifications, such as 0, 1, 2 or 3 modifications; e) the heavy chain comprises a heavy chain variable region (HCVR), the heavy chain variable region comprises CDRH1, CDRH2 and CDRH3, and wherein CDRH1, CDRH2 and CDRH3 comprise the sequences shown in SEQ ID NOs: 11, 12 and 13, respectively, each having 0 to 3 amino acid modifications, such as 0, 1, 2 or 3 modifications; and the light chain comprises a light chain variable region (LCVR), the light chain variable region comprises CDRL1, CDRL2 and CDRL3, and wherein CDRL1, CDRL2 and CDRL3 comprise the sequences shown in SEQ ID NOs: 14, 15 and 16, respectively, each having 0 to 3 amino acid modifications, such as 0, 1, 2 or 3 modifications; f) the heavy chain comprises a heavy chain variable region (HCVR), comprising CDRH1, CDRH2 and CDRH3, and wherein CDRH1, CDRH2 and CDRH3 comprise the sequences shown in SEQ ID NOs: 19, 20 and 21, respectively, each having 0 to 3 amino acid modifications, such as 0, 1, 2 or 3 modifications; and the light chain comprises a light chain variable region (LCVR), comprising CDRL1, CDRL2 and CDRL3, and wherein CDRL1, CDRL2 and CDRL3 comprise the sequences shown in SEQ ID NOs: 22, 23 and 24, respectively, each having 0 to 3 amino acid modifications, such as 0, 1, 2 or 3 modifications; g) the heavy chain comprises a heavy chain variable region (HCVR), comprising CDRH1, CDRH2 and CDRH3, and wherein CDRH1, CDRH2 and CDRH3 comprise the sequences shown in SEQ ID NOs: 27, 28 and 29, respectively, each having 0 to 3 amino acid modifications, such as 0, 1, 2 or 3 modifications; and the light chain comprises a light chain variable region (LCVR), comprising CDRL1, CDRL2 and CDRL3, and wherein CDRL1, CDRL2 and CDRL3 comprise the sequences shown in SEQ ID NOs: 30, 31 and 32, respectively, each having 0 to 3 amino acid modifications, such as 0, 1, 2 or 3 modifications; h) the heavy chain comprises a heavy chain variable region (HCVR), comprising CDRH1, CDRH2 and CDRH3, and wherein CDRH1, CDRH2 and CDRH3 comprise the sequences shown in SEQ ID NOs: 35, 36 and 37, respectively, each having 0 to 3 amino acid modifications, such as 0, 1, 2 or 3 modifications; and the light chain comprises a light chain variable region (LCVR), comprising CDRL1, CDRL2 and CDRL3, and wherein CDRL1, CDRL2 and CDRL3 comprise the sequences shown in SEQ ID NOs: 38, 39 and 40, respectively, each having 0 to 3 amino acid modifications, such as 0, 1, 2 or 3 modifications; i) the heavy chain comprises a heavy chain variable region (HCVR), comprising a heavy chain complementary determining region 1 (CDRH1), CDRH2 and CDRH3, wherein CDRH1, CDRH2 and CDRH3 comprise the sequences shown in SEQ ID NOs: 3, 4 and 5, respectively, each having 0 to 3 amino acid modifications, such as 0, 1, 2 or 3 modifications; and the light chain comprises a light chain variable region (LCVR), comprising a light chain complementary determining region 1 (CDRL1), CDRL2 and CDRL3, wherein CDRL1, CDRL2 and CDRL3 comprise the sequences shown in SEQ ID NOs: 6, 67 and 8, respectively, each having 0 to 3 amino acid modifications, such as 0, 1, 2 or 3 modifications; j) the heavy chain comprises a heavy chain variable region (HCVR), comprising a heavy chain complementary determining region 1 (CDRH1), CDRH2 and CDRH3, wherein CDRH1, CDRH2 and CDRH3 comprise the sequences shown in SEQ ID NOs: 3, 41 and 69, respectively, each having 0 to 3 amino acid modifications, such as 0, 1, 2 or 3 modifications; and the light chain comprises a light chain variable region (LCVR), comprising a light chain complementary determining region 1 (CDRL1), CDRL2 and CDRL3, wherein CDRL1, CDRL2 and CDRL3 comprise the sequences shown in SEQ ID NOs: 6, 67 and 8, respectively, each having 0 to 3 amino acid modifications, such as 0, 1, 2 or 3 modifications; k) the heavy chain comprises a heavy chain variable region (HCVR), comprising a heavy chain complementary determining region 1 (CDRH1), CDRH2 and CDRH3, wherein CDRH1, CDRH2 and CDRH3 comprise the sequences shown in SEQ ID NOs: 3, 41 and 70, respectively, each having 0 to 3 amino acid modifications, such as 0, 1, 2 or 3 modifications; and the light chain comprises a light chain variable region (LCVR), comprising a light chain complementary determining region 1 (CDRL1), CDRL2 and CDRL3, wherein CDRL1, CDRL2 and CDRL3 comprise the sequences shown in SEQ ID NOs: 6, 67 and 8, respectively, each having 0 to 3 amino acid modifications, such as 0, 1, 2 or 3 modifications; or l) the heavy chain comprises a heavy chain variable region (HCVR), comprising a heavy chain complementary determining region 1 (CDRH1), CDRH2 and CDRH3, wherein CDRH1, CDRH2 and CDRH3 respectively comprise the sequences shown in SEQ ID NOs:3, 4 and 5, each having 0 to 3 amino acid modifications, such as 0, 1, 2 or 3 modifications; and the light chain comprises a light chain variable region (LCVR), comprising a light chain complementary determining region 1 (CDRL1), CDRL2 and CDRL3, wherein CDRL1, CDRL2 and CDRL3 respectively comprise the sequences shown in SEQ ID NOs:6, 68 and 8, each having 0 to 3 amino acid modifications, such as 0, 1, 2 or 3 modifications.

6. The antibody or antigen-binding fragment thereof of any of the preceding claims, wherein the HCVR comprises an amino acid sequence having at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence shown in SEQ ID NO: 1, 9, 17, 25, 33, 42, 43, 44, 45, 46, 47, 71, 72 or 93.

7. The antibody or antigen-binding fragment thereof according to any of the preceding claims, wherein the HCVR comprises the amino acid sequence as shown in SEQ ID NO: 1, 9, 17, 25, 33, 42, 43, 44, 45, 46, 47, 71, 72 or 93, having 0 to 10 amino acid modifications, such as 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid modifications.

8. The antibody or antigen-binding fragment thereof of any of the preceding claims, wherein the LCVR comprises an amino acid sequence having at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence shown in SEQ ID NO: 2, 10, 18, 26, 34, 48, 49, 50, 51, 52, 65, 66 or 94.

9. The antibody or antigen-binding fragment thereof according to any of the preceding claims, wherein the LCVR comprises the amino acid sequence as shown in SEQ ID NO: 2, 10, 18, 26, 34, 48, 49, 50, 51, 52, 65, 66 or 94, having 0 to 10 amino acid modifications, such as 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid modifications.

10. The antibody or antigen-binding fragment thereof according to any one of the preceding claims, wherein: a) the HCVR comprises an amino acid sequence that has at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence set forth in SEQ ID NO:72, and the LCVR comprises an amino acid sequence that has at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence set forth in SEQ ID NO:65; b) the HCVR comprises an amino acid sequence that has at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence set forth in SEQ ID NO:71, and the LCVR comprises an amino acid sequence that has at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence set forth in SEQ ID NO:65; c) the HCVR comprises an amino acid sequence that has at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence set forth in SEQ ID NO: 1, and the LCVR comprises an amino acid sequence that has at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence set forth in SEQ ID NO: 2; d) the HCVR comprises an amino acid sequence that has at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence set forth in SEQ ID NO:9, and the LCVR comprises an amino acid sequence that has at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence set forth in SEQ ID NO:10; e) the HCVR comprises an amino acid sequence that has at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence set forth in SEQ ID NO: 17, and the LCVR comprises an amino acid sequence that has at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence set forth in SEQ ID NO: 18; f) the HCVR comprises an amino acid sequence that has at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence set forth in SEQ ID NO:25, and the LCVR comprises an amino acid sequence that has at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence set forth in SEQ ID NO:26; g) the HCVR comprises an amino acid sequence that has at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence set forth in SEQ ID NO:33, and the LCVR comprises an amino acid sequence that has at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence set forth in SEQ ID NO:34; h) the HCVR comprises an amino acid sequence that has at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence set forth in any one of SEQ ID NOs: 1, 42, 43, 44, 45, 46, 47, 71, 72 or 93, and the LCVR comprises an amino acid sequence that has at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence set forth in any one of SEQ ID NOs: 2, 48, 49, 50, 51, 52, 65, 66 or 94; or i) the HCVR comprises an amino acid sequence that has at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence set forth in SEQ ID NO:42, 43, 44, 45, 46, 47, 71, 72 or 93, and the LCVR comprises an amino acid sequence that has at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence set forth in SEQ ID NO:48, 49, 50, 51, 52, 65, 66 or 94.

11. The antibody or antigen-binding fragment thereof according to any one of the preceding claims, wherein: a) the HCVR comprises the amino acid sequence as set forth in SEQ ID NO:72, having 0 to 10 amino acid modifications, such as 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid modifications, and the LCVR comprises the amino acid sequence as set forth in SEQ ID NO:65, having 0 to 10 amino acid modifications, such as 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid modifications; b) the HCVR comprises the amino acid sequence as set forth in SEQ ID NO:71, having 0 to 3 amino acid modifications, and the LCVR comprises the amino acid sequence as set forth in SEQ ID NO:65, having 0 to 3 amino acid modifications; c) the HCVR comprises the amino acid sequence as set forth in SEQ ID NO: 1, having 0 to 10 amino acid modifications, such as 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid modifications, and the LCVR comprises the amino acid sequence as set forth in SEQ ID NO: 2, having 0 to 10 amino acid modifications, such as 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid modifications; d) the HCVR comprises the amino acid sequence as set forth in SEQ ID NO:9, having 0 to 10 amino acid modifications, such as 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid modifications, and the LCVR comprises the amino acid sequence as set forth in SEQ ID NO:10, having 0 to 10 amino acid modifications, such as 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid modifications; e) the HCVR comprises the amino acid sequence as set forth in SEQ ID NO: 17, having 0 to 10 amino acid modifications, such as 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid modifications, and the LCVR comprises the amino acid sequence as set forth in SEQ ID NO: 18, having 0 to 10 amino acid modifications, such as 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid modifications; f) the HCVR comprises the amino acid sequence as set forth in SEQ ID NO:25, having 0 to 10 amino acid modifications, such as 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid modifications, and the LCVR comprises the amino acid sequence as set forth in SEQ ID NO:26, having 0 to 10 amino acid modifications, such as 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid modifications; g) the HCVR comprises the amino acid sequence as set forth in SEQ ID NO:33, having 0 to 3 amino acid modifications, and the LCVR comprises the amino acid sequence as set forth in SEQ ID NO:34, having 0 to 3 amino acid modifications; h) the HCVR comprises an amino acid sequence as shown in any one of SEQ ID NO: 1, 42, 43, 44, 45, 46, 47, 71, 72 or 93, having 0 to 10 amino acid modifications, such as 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid modifications, and the LCVR comprises an amino acid sequence as shown in SEQ ID NO: 2, 48, 49, 50, 51, 52, 65, 66 or 94, having 0 to 10 amino acid modifications, such as 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid modifications; or i) the HCVR comprises an amino acid sequence as shown in any one of SEQ ID NOs: 42, 43, 44, 45, 46, 47, 71, 72 or 93, having 0 to 10 amino acid modifications, such as 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid modifications, and the LCVR comprises an amino acid sequence as shown in SEQ ID NOs: 48, 49, 50, 51, 52, 65, 66 or 94, having 0 to 10 amino acid modifications, such as 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid modifications.

12. An antibody or antigen-binding fragment thereof that specifically binds to CD200R, wherein the antibody or antigen-binding fragment thereof comprises a heavy chain comprising a heavy chain variable region (HCVR), and wherein the HCVR comprises an amino acid sequence having at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence shown in SEQ ID NO: 1, 9, 17, 25, 33, 42, 43, 44, 45, 46, 47, 71, 72 or 93.

13. An antibody or antigen-binding fragment thereof that specifically binds to CD200R, wherein the antibody or antigen-binding fragment thereof comprises a heavy chain variable region (HCVR), and wherein the HCVR comprises the amino acid sequence shown in SEQ ID NO: 1, 9, 17, 25, 33, 42, 43, 44, 45, 46, 47, 71, 72 or 93, having 0 to 10 amino acid modifications, such as 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid modifications.

14. An antibody or antigen-binding fragment thereof that specifically binds to CD200R, wherein the antibody or antigen-binding fragment thereof comprises a light chain comprising a light chain variable region (LCVR), and wherein the LCVR comprises an amino acid sequence having at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence shown in SEQ ID NO: 2, 10, 18, 26, 34, 48, 49, 50, 51, 52, 65, 66 or 94.

15. An antibody or antigen-binding fragment thereof that specifically binds to CD200R, wherein the antibody or antigen-binding fragment thereof comprises a light chain comprising a light chain variable region (LCVR), and wherein the LCVR comprises the amino acid sequence shown in SEQ ID NO: 2, 10, 18, 26, 34, 48, 49, 50, 51, 52, 65, 66 or 94, having 0 to 10 amino acid modifications, such as 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid modifications.

16. An antibody or antigen-binding fragment thereof that specifically binds to CD200R, the antibody or antigen-binding fragment thereof comprising a heavy chain and a light chain, wherein the heavy chain comprises a heavy chain variable region (HCVR), and the light chain comprises a light chain variable region (LCVR), wherein: a) the HCVR comprises an amino acid sequence that has at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence set forth in SEQ ID NO:72, and the LCVR comprises an amino acid sequence that has at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence set forth in SEQ ID NO:65; b) the HCVR comprises an amino acid sequence that has at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence set forth in SEQ ID NO:71, and the LCVR comprises an amino acid sequence that has at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence set forth in SEQ ID NO:65; c) the HCVR comprises an amino acid sequence that has at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence set forth in SEQ ID NO: 1, and the LCVR comprises an amino acid sequence that has at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence set forth in SEQ ID NO: 2; d) the HCVR comprises an amino acid sequence that has at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence set forth in SEQ ID NO:9, and the LCVR comprises an amino acid sequence that has at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence set forth in SEQ ID NO:10; e) the HCVR comprises an amino acid sequence that has at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence set forth in SEQ ID NO: 17, and the LCVR comprises an amino acid sequence that has at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence set forth in SEQ ID NO: 18; f) the HCVR comprises an amino acid sequence that has at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence set forth in SEQ ID NO:25, and the LCVR comprises an amino acid sequence that has at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence set forth in SEQ ID NO:26; g) the HCVR comprises an amino acid sequence that has at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence set forth in SEQ ID NO:33, and the LCVR comprises an amino acid sequence that has at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence set forth in SEQ ID NO:34; h) the HCVR comprises an amino acid sequence that has at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence set forth in any one of SEQ ID NOs: 1, 42, 43, 44, 45, 46, 47, 71, 72 or 93, and the LCVR comprises an amino acid sequence that has at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence set forth in any one of SEQ ID NOs: 2, 48, 49, 50, 51, 52, 65, 66 or 94; or i) the HCVR comprises an amino acid sequence that has at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence set forth in SEQ ID NO:42, 43, 44, 45, 46, 47, 71, 72 or 93, and the LCVR comprises an amino acid sequence that has at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence set forth in SEQ ID NO:48, 49, 50, 51, 52, 65, 66 or 94.

17. An antibody or antigen-binding fragment thereof that specifically binds to CD200R, the antibody or antigen-binding fragment thereof comprising a heavy chain and a light chain, wherein the heavy chain comprises a heavy chain variable region and the light chain comprises a light chain variable region, wherein: a) the heavy chain variable region comprises the amino acid sequence as shown in SEQ ID NO: 72, having 0 to 10 amino acid modifications, such as 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid modifications, and the light chain variable region comprises the amino acid sequence as shown in SEQ ID NO: 65, having 0 to 10 amino acid modifications, such as 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid modifications; b) the heavy chain variable region comprises the amino acid sequence as shown in SEQ ID NO:71, having 0 to 10 amino acid modifications, such as 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid modifications, and the light chain variable region comprises the amino acid sequence as shown in SEQ ID NO:65, having 0 to 10 amino acid modifications, such as 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid modifications; c) the heavy chain variable region comprises the amino acid sequence as shown in SEQ ID NO: 1, with 0 to 10 amino acid modifications, such as 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid modifications, and the light chain variable region comprises the amino acid sequence as shown in SEQ ID NO: 2, with 0 to 10 amino acid modifications, such as 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid modifications; d) the heavy chain variable region comprises the amino acid sequence as shown in SEQ ID NO:9, having 0 to 10 amino acid modifications, such as 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid modifications, and the light chain variable region comprises the amino acid sequence as shown in SEQ ID NO:10, having 0 to 10 amino acid modifications, such as 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid modifications; e) the heavy chain variable region comprises the amino acid sequence as shown in SEQ ID NO: 17, having 0 to 10 amino acid modifications, such as 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid modifications, and the light chain variable region comprises the amino acid sequence as shown in SEQ ID NO: 18, having 0 to 10 amino acid modifications, such as 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid modifications; f) the heavy chain variable region comprises the amino acid sequence as shown in SEQ ID NO: 25, having 0 to 10 amino acid modifications, such as 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid modifications, and the light chain variable region comprises the amino acid sequence as shown in SEQ ID NO: 26, having 0 to 10 amino acid modifications, such as 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid modifications; g) the heavy chain variable region comprises the amino acid sequence as shown in SEQ ID NO: 33, having 0 to 10 amino acid modifications, such as 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid modifications, and the light chain variable region comprises the amino acid sequence as shown in SEQ ID NO: 34, having 0 to 10 amino acid modifications, such as 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid modifications; h) the heavy chain variable region comprises the amino acid sequence shown in any one of SEQ ID NO: 1, 42, 43, 44, 45, 46, 47, 71, 72 or 93, having 0 to 10 amino acid modifications, such as 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid modifications, and the light chain variable region comprises the amino acid sequence shown in SEQ ID NO: 2, 48, 49, 50, 51, 52, 65, 66 or 94, having 0 to 10 amino acid modifications, such as 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid modifications; or i) the heavy chain variable region comprises an amino acid sequence as shown in any one of SEQ ID NO:42, 43, 44, 45, 46, 47, 71, 72 or 93, having 0 to 10 amino acid modifications, such as 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid modifications, and the light chain variable region comprises an amino acid sequence as shown in SEQ ID NO:48, 49, 50, 51, 52, 65, 66 or 94, having 0 to 10 amino acid modifications, such as 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid modifications.

18. An antibody or antigen-binding fragment thereof, wherein the antibody or antigen-binding fragment thereof comprises a heavy chain variable region (HCVR) and a light chain variable region (LCVR), wherein: a) the HCVR comprises a heavy chain complementary determining region 1 (CDRH1), CDRH2 and CDRH3, and wherein CDRH1, CDRH2 and CDRH3 respectively comprise the sequences shown in SEQ ID NOs: 3, 41 and 70 each having 0 to 3 amino acid modifications, such as 0, 1, 2 or 3 modifications; and b) the LCVR comprises a light chain complementary determining region 1 (CDRL1), CDRL2 and CDRL3, and wherein CDRL1, CDRL2 and CDRL3 comprise the sequences shown in SEQ ID NOs: 6, 67 and 8, respectively, each having 0 to 3 amino acid modifications, such as 0, 1, 2 or 3 modifications.

19. The antibody or antigen-binding fragment thereof according to claim 18, wherein: a) the HCVR comprises an amino acid sequence that has at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence set forth in SEQ ID NO:72, and the LCVR comprises an amino acid sequence that has at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence set forth in SEQ ID NO:65; or b) the HCVR comprises the amino acid sequence as shown in SEQ ID NO:72, having 0 to 10 amino acid modifications, such as 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid modifications, and the LCVR comprises the amino acid sequence as shown in SEQ ID NO:65, having 0 to 10 amino acid modifications, such as 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid modifications.

20. An antibody or antigen-binding fragment thereof, wherein the antibody or antigen-binding fragment thereof comprises a heavy chain variable region (HCVR) and a light chain variable region (LCVR), wherein: a) the HCVR comprises a heavy chain complementary determining region 1 (CDRH1), CDRH2 and CDRH3, and wherein CDRH1, CDRH2 and CDRH3 comprise the sequences shown in SEQ ID NOs: 3, 41 and 5, respectively, each having 0 to 3 amino acid modifications, such as 0, 1, 2 or 3 modifications; and b) the LCVR comprises a light chain complementary determining region 1 (CDRL1), CDRL2 and CDRL3, and wherein CDRL1, CDRL2 and CDRL3 comprise the sequences shown in SEQ ID NOs: 6, 67 and 8, respectively, each having 0 to 3 amino acid modifications, such as 0, 1, 2 or 3 modifications.

21. The antibody or antigen-binding fragment thereof according to claim 20, wherein: a) the HCVR comprises an amino acid sequence that has at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence set forth in SEQ ID NO:71, and the LCVR comprises an amino acid sequence that has at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence set forth in SEQ ID NO:65; or b) the HCVR comprises the amino acid sequence as shown in SEQ ID NO:71, having 0 to 10 amino acid modifications, such as 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid modifications, and the LCVR comprises the amino acid sequence as shown in SEQ ID NO:65, having 0 to 10 amino acid modifications, such as 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid modifications.

22. An antibody or antigen-binding fragment thereof that specifically binds to CD200R, the antibody or antigen-binding fragment thereof comprising a heavy chain and a light chain, wherein the heavy chain comprises a heavy chain variable region (HCVR), wherein the light chain comprises a light chain variable region (LCVR), wherein: (a) the HCVR comprises an amino acid sequence that has at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence set forth in SEQ ID NO:72, and the LCVR comprises an amino acid sequence that has at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence set forth in SEQ ID NO:65, wherein the HCVR comprises a heavy chain complementary determining region 1 (CDRH1), CDRH2, and CDRH3, and wherein CDRH1, CDRH2, and CDRH3 comprise the sequences set forth in SEQ ID NOs:3, 41, and 70, respectively; and the LCVR comprises a light chain complementary determining region 1 (CDRL1), CDRL2, and CDRL3, and wherein CDRL1, CDRL2, and CDRL3 comprise the sequences set forth in SEQ ID NOs:6, 67, and 8, respectively; (b) the HCVR comprises the amino acid sequence of SEQ ID NO:72, having 0 to 10 amino acid modifications, such as 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid modifications, and the LCVR comprises the amino acid sequence of SEQ ID NO:65, having 0 to 10 amino acid modifications, such as 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid modifications, wherein the HCVR comprises a heavy chain complementary determining region 1 (CDRH1), CDRH2 and CDRH3, and wherein CDRH1, CDRH2 and CDRH3 comprise the sequences of SEQ ID NOs:3, 41 and 70, respectively; and the LCVR comprises a light chain complementary determining region 1 (CDRL1), CDRL2 and CDRL3, and wherein CDRL1, CDRL2 and CDRL3 comprise the sequences of SEQ ID NOs:6, 67 and 8, respectively; (c) the HCVR comprises an amino acid sequence that has at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence set forth in SEQ ID NO:71, and the LCVR comprises an amino acid sequence that has at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence set forth in SEQ ID NO:65, wherein the HCVR comprises a heavy chain complementary determining region 1 (CDRH1), CDRH2, and CDRH3, and wherein CDRH1, CDRH2, and CDRH3 comprise the sequences set forth in SEQ ID NOs:3, 41, and 5, respectively; and the LCVR comprises a light chain complementary determining region 1 (CDRL1), CDRL2, and CDRL3, and wherein CDRL1, CDRL2, and CDRL3 comprise the sequences set forth in SEQ ID NOs:6, 67, and 8, respectively; (d) the HCVR comprises the amino acid sequence of SEQ ID NO:71, having 0 to 10 amino acid modifications, such as 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid modifications, and the LCVR comprises the amino acid sequence of SEQ ID NO:65, having 0 to 10 amino acid modifications, such as 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid modifications, wherein the HCVR comprises a heavy chain complementary determining region 1 (CDRH1), CDRH2 and CDRH3, and wherein CDRH1, CDRH2 and CDRH3 comprise the sequences of SEQ ID NOs:3, 41 and 5, respectively; and the LCVR comprises a light chain complementary determining region 1 (CDRL1), CDRL2 and CDRL3, and wherein CDRL1, CDRL2 and CDRL3 comprise the sequences of SEQ ID NOs:6, 67 and 8, respectively; (e) the HCVR comprises an amino acid sequence that has at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence set forth in SEQ ID NO:93, and the LCVR comprises an amino acid sequence that has at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence set forth in SEQ ID NO:94, wherein the HCVR comprises a heavy chain complementary determining region 1 (CDRH1), CDRH2, and CDRH3, and wherein CDRH1, CDRH2, and CDRH3 comprise the sequences set forth in SEQ ID NOs:92, 41, and 69, respectively; and the LCVR comprises a light chain complementary determining region 1 (CDRL1), CDRL2, and CDRL3, and wherein CDRL1, CDRL2, and CDRL3 comprise the sequences set forth in SEQ ID NOs:6, 87, and 91, respectively; or (f) the HCVR comprises the amino acid sequence of SEQ ID NO:93, having 0 to 10 amino acid modifications, such as 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid modifications, and the LCVR comprises the amino acid sequence of SEQ ID NO:94, having 0 to 10 amino acid modifications, such as 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid modifications, wherein the HCVR comprises a heavy chain complementary determining region 1 (CDRH1), CDRH2 and CDRH3, and wherein CDRH1, CDRH2 and CDRH3 comprise the sequences of SEQ ID NOs:92, 41 and 69, respectively; and the LCVR comprises a light chain complementary determining region 1 (CDRL1), CDRL2 and CDRL3, and wherein CDRL1, CDRL2 and CDRL3 comprise the sequences of SEQ ID NOs:6, 87 and 91, respectively.

23. An antibody or antigen-binding fragment thereof that specifically binds to CD200R, the antibody or antigen-binding fragment thereof comprising (a) a heavy chain, wherein the heavy chain comprises a heavy chain variable region (HCVR) of SEQ ID NO: 72, and (b) a light chain, wherein the light chain comprises a light chain variable region (LCVR) of SEQ ID NO:

65.

24. An antibody or antigen-binding fragment thereof that specifically binds to CD200R, the antibody or antigen-binding fragment thereof comprising (a) a heavy chain, wherein the heavy chain comprises a heavy chain variable region (HCVR) of SEQ ID NO: 71, and (b) a light chain, wherein the light chain comprises a light chain variable region (LCVR) of SEQ ID NO:

65.

25. An antibody or antigen-binding fragment thereof that specifically binds to CD200R, the antibody or antigen-binding fragment thereof comprising (a) a heavy chain, wherein the heavy chain comprises a heavy chain variable region (HCVR) of SEQ ID NO: 93, and (b) a light chain, wherein the light chain comprises a light chain variable region (LCVR) of SEQ ID NO:

94.

26. The antibody or antigen-binding fragment thereof of claim 22(e), 22(f) or 25, wherein: (a) X at position 1 of SEQ ID NO:93 is D; (b) X at position 1 of SEQ ID NO:93 is E; (c) X at position 33 of SEQ ID NO:93 is W; (d) X at position 33 of SEQ ID NO:93 is F; (e) X at position 99 of SEQ ID NO:93 is M; (f) X at position 99 of SEQ ID NO:93 is G; (g) X at position 50 of SEQ ID NO:94 is G; (h) X at position 50 of SEQ ID NO:94 is L; (i) X at position 51 of SEQ ID NO:94 is A; (j) X at position 51 of SEQ ID NO:94 is G; (k) X at position 52 of SEQ ID NO:94 is S; (l) X at position 52 of SEQ ID NO:94 is V; (m) X at position 56 of SEQ ID NO:94 is D; (n) X at position 56 of SEQ ID NO:94 is S; (o) X at position 56 of SEQ ID NO:94 is T; (p) X at position 96 of SEQ ID NO:94 is W; (q) X at position 96 of SEQ ID NO:94 is F; or (r) Any combination of (a) to (q).

27. The antibody or antigen-binding fragment thereof according to claim 22(e) or 22(f), wherein: (a) X at position 1 of SEQ ID NO:69 is M; (b) X at position 1 of SEQ ID NO:69 is G; (c) X at position 8 of SEQ ID NO:91 is W; (d) X at position 8 of SEQ ID NO:91 is F; (e) X at position 3 of SEQ ID NO:92 is W; (f) X at position 3 of SEQ ID NO:92 is F; (g) X at position 1 of SEQ ID NO:87 is G; (h) X at position 1 of SEQ ID NO:87 is L; (i) X at position 2 of SEQ ID NO:87 is A; (j) X at position 2 of SEQ ID NO:87 is G; (k) X at position 3 of SEQ ID NO:87 is S; (l) X at position 3 of SEQ ID NO:87 is V; (m) X at position 7 of SEQ ID NO:87 is D; (n) X at position 7 of SEQ ID NO:87 is S; (o) X at position 7 of SEQ ID NO:87 is T; or (p) Any combination of (a) to (o).

28. The antibody or antigen-binding fragment thereof according to any one of the preceding claims, wherein the heavy chain or the light chain further comprises a constant region.

29. The antibody or antigen-binding fragment thereof according to any one of the preceding claims, wherein the heavy chain and the light chain are connected by a flexible linker to form a single chain antibody.

30. The antibody or antigen-binding fragment thereof of any one of claims 1 to 29, wherein the LCVR is linked to a light chain constant region comprising an amino acid sequence having at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence shown in SEQ ID NO:

62.

31. An antibody or antigen-binding fragment thereof according to any one of claims 1 to 29, wherein the light chain variable region is connected to a light chain constant region, and the light chain constant region comprises the amino acid sequence shown in SEQ ID NO: 62, with 0 to 10 amino acid modifications, such as 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid modifications.

32. An antibody or antigen-binding fragment thereof according to any one of claims 1 to 29, wherein the light chain variable region is connected to a light chain constant region, and the light chain constant region comprises an amino acid sequence having at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity with the amino acid sequence shown in SEQ ID NO:

64.

33. An antibody or antigen-binding fragment thereof according to any one of claims 1 to 29, wherein the light chain variable region is connected to a light chain constant region, and the light chain constant region comprises the amino acid sequence shown in SEQ ID NO: 64, with 0 to 10 amino acid modifications, such as 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid modifications.

34. The antibody or antigen-binding fragment thereof of any one of claims 1 to 33, wherein the HCVR is linked to a heavy chain constant region comprising an amino acid sequence having at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence shown in SEQ ID NO: 61, 63, 75 and 76.

35. The antibody or antigen-binding fragment thereof of any one of claims 1 to 33, wherein the HCVR is linked to a heavy chain constant region comprising an amino acid sequence having at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence shown in SEQ ID NO: 61, 75 and 76.

36. The antibody or antigen-binding fragment thereof according to any one of claims 1 to 33, wherein the HCVR is linked to a heavy chain constant region comprising the amino acid sequence shown in SEQ ID NO: 61, 63, 75 and 76, with 0 to 10 amino acid modifications, such as 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid modifications.

37. The antibody or antigen-binding fragment thereof according to any one of claims 1 to 33, wherein the HCVR is linked to a heavy chain constant region comprising the amino acid sequence shown in SEQ ID NO: 61, 75 and 76, with 0 to 10 amino acid modifications, such as 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid modifications.

38. An antibody or an antigen-binding fragment thereof that specifically binds to CD200R, the antibody or the antigen-binding fragment thereof comprising (a) a heavy chain of SEQ ID NO: 82 and (b) a light chain of SEQ ID NO:

86.

39. An antibody or an antigen-binding fragment thereof that specifically binds to CD200R, the antibody or the antigen-binding fragment thereof comprising (a) a heavy chain of SEQ ID NO: 83 and (b) a light chain of SEQ ID NO:

86.

40. An antibody or an antigen-binding fragment thereof that specifically binds to CD200R, the antibody or the antigen-binding fragment thereof comprising (a) a heavy chain of SEQ ID NO: 84 and (b) a light chain of SEQ ID NO:

86.

41. An antibody or an antigen-binding fragment thereof that specifically binds to CD200R, the antibody or the antigen-binding fragment thereof comprising (a) a heavy chain of SEQ ID NO: 85 and (b) a light chain of SEQ ID NO:

86.

42. An antibody or an antigen-binding fragment thereof that specifically binds to CD200R, the antibody or the antigen-binding fragment thereof comprising (a) a heavy chain of SEQ ID NO: 95 and (b) a light chain of SEQ ID NO:

98.

43. The antibody or antigen-binding fragment thereof according to claim 42, wherein: (a) X at position 1 of SEQ ID NO:95 is D; (b) X at position 1 of SEQ ID NO:95 is E; (c) X at position 33 of SEQ ID NO:95 is W; (d) X at position 33 of SEQ ID NO:95 is F; (e) X at position 99 of SEQ ID NO:95 is M; (f) X at position 99 of SEQ ID NO:95 is G; (g) X at position 235 of SEQ ID NO:95 is D; (h) X at position 235 of SEQ ID NO:95 is P; (i) X at position 443 of SEQ ID NO:95 is G; (j) X at positions 443 and 444 of SEQ ID NO:95 is absent; (k) X at position 444 of SEQ ID NO:95 is K; (l) X at position 444 of SEQ ID NO:95 is absent; or (m) Any combination of (a) to (l).

44. An antibody or an antigen-binding fragment thereof that specifically binds to CD200R, the antibody or the antigen-binding fragment thereof comprising (a) a heavy chain of SEQ ID NO: 96 and (b) a light chain of SEQ ID NO:

98.

45. The antibody or antigen-binding fragment thereof according to claim 44, wherein: (a) X at position 1 of SEQ ID NO:96 is D; (b) X at position 1 of SEQ ID NO:96 is E; (c) X at position 33 of SEQ ID NO:96 is W; (d) X at position 33 of SEQ ID NO:96 is F; (e) X at position 99 of SEQ ID NO:96 is M; (f) X at position 99 of SEQ ID NO:96 is G; (g) X at position 222 of SEQ ID NO:96 is S; (h) X at position 222 of SEQ ID NO:96 is P; (i) X at position 440 of SEQ ID NO:96 is G; (j) X at positions 440 and 441 of SEQ ID NO:96 is absent; (k) X at position 441 of SEQ ID NO:96 is K; (l) the X at position 441 of SEQ ID NO:96 is absent; or (m) Any combination of (a) to (l).

46. ​​An antibody or an antigen-binding fragment thereof that specifically binds to CD200R, the antibody or the antigen-binding fragment thereof comprising (a) the heavy chain of SEQ ID NO: 97 and (b) the light chain of SEQ ID NO:

98.

47. The antibody or antigen-binding fragment thereof according to claim 46, wherein: (a) X at position 1 of SEQ ID NO:97 is D; (b) X at position 1 of SEQ ID NO:97 is E; (c) X at position 33 of SEQ ID NO:97 is W; (d) X at position 33 of SEQ ID NO:97 is F; (e) X at position 99 of SEQ ID NO:97 is M; (f) X at position 99 of SEQ ID NO:97 is G; (g) X at position 437 of SEQ ID NO:97 is G; (h) X at positions 437 and 438 of SEQ ID NO:97 is absent; (i) X at position 438 of SEQ ID NO:97 is K; (j) X at position 438 of SEQ ID NO:97 is absent; or (k) Any combination of (a) to (j).

48. The antibody or antigen-binding fragment thereof according to any one of claims 42 to 47, wherein: (a) X at position 50 of SEQ ID NO:98 is G; (b) X at position 50 of SEQ ID NO:98 is L; (c) X at position 51 of SEQ ID NO:98 is A; (d) X at position 51 of SEQ ID NO:98 is G; (e) X at position 52 of SEQ ID NO:98 is S; (f) X at position 52 of SEQ ID NO:98 is V; (g) X at position 56 of SEQ ID NO:98 is D; (h) X at position 56 of SEQ ID NO:98 is S; (i) X at position 56 of SEQ ID NO:98 is T; (j) X at position 96 of SEQ ID NO:98 is W; (k) X at position 96 of SEQ ID NO:98 is F; or (l) Any combination of (a) to (k).

49. The antibody or antigen-binding fragment thereof of any preceding claim, wherein the HCVR is linked to a heavy chain constant region, wherein the heavy chain constant region comprises an Fc region comprising one or more of the following amino acids: alanine at position 234 (A), alanine at position 235 (A), aspartic acid at position 236 (D), aspartic acid at position 237 (D), aspartic acid at position 238 (D), alanine at position 265 (A), glutamic acid at position 267 (E), glycine at position 271 (G), arginine at position 330 (R), alanine at position 332 (A), or alanine at position 297 (A) (numbering according to the EU index).

50. The antibody or antigen-binding fragment thereof of claim 49, wherein the Fc region comprises aspartic acid (D) at position 238 (EU index).

51. The antibody or antigen-binding fragment thereof of any one of claims 1 to 33, wherein the HCVR is linked to a heavy chain constant region comprising an amino acid sequence having at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence shown in SEQ ID NO:

77.

52. The antibody or antigen-binding fragment thereof of any one of claims 1 to 33, wherein the HCVR is linked to a heavy chain constant region comprising the amino acid sequence as shown in SEQ ID NO: 77, having 0 to 10 amino acid modifications, such as 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid modifications.

53. The antibody or antigen-binding fragment thereof according to any one of claims 51 to 52, wherein X at position 121 of SEQ ID NO:77 is D.

54. The antibody or antigen-binding fragment thereof according to any one of claims 51 to 52, wherein X at position 121 of SEQ ID NO:77 is P.

55. The antibody or antigen-binding fragment thereof according to any one of claims 51 to 54, wherein X at position 329 of SEQ ID NO:77 is G.

56. The antibody or antigen-binding fragment thereof according to any one of claims 51 to 54, wherein the X at position 329 of SEQ ID NO: 77 is absent.

57. The antibody or antigen-binding fragment thereof according to any one of claims 51 to 55, wherein X at position 330 of SEQ ID NO:77 is K.

58. The antibody or antigen-binding fragment thereof according to any one of claims 51 to 56, wherein the X at position 330 of SEQ ID NO: 77 is absent.

59. The antibody or antigen-binding fragment thereof of any one of claims 1 to 33, wherein the HCVR is linked to a heavy chain constant region comprising an amino acid sequence having at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence shown in SEQ ID NO:

78.

60. An antibody or antigen-binding fragment thereof according to any one of claims 1 to 33, wherein the heavy chain variable region is connected to a heavy chain constant region, and the heavy chain constant region comprises the amino acid sequence shown in SEQ ID NO: 78, with 0 to 10 amino acid modifications, such as 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid modifications.

61. The antibody or antigen-binding fragment thereof according to any one of claims 59 to 60, wherein X at position 108 of SEQ ID NO:78 is S.

62. The antibody or antigen-binding fragment thereof according to any one of claims 59 to 60, wherein X at position 108 of SEQ ID NO:78 is P.

63. The antibody or antigen-binding fragment thereof according to any one of claims 59 to 62, wherein X at position 326 of SEQ ID NO:78 is G.

64. The antibody or antigen-binding fragment thereof according to any one of claims 59 to 62, wherein the X at position 326 of SEQ ID NO: 78 is absent.

65. The antibody or antigen-binding fragment thereof according to any one of claims 59 to 63, wherein X at position 327 of SEQ ID NO:78 is K.

66. The antibody or antigen-binding fragment thereof according to any one of claims 59 to 64, wherein the X at position 327 of SEQ ID NO: 78 is absent.

67. The antibody or antigen binding fragment thereof according to any one of claims 1 to 33, wherein the antibody or antigen binding fragment thereof is an IgG, IgM, IgE, IgA or IgD molecule, or is derived from one of these.

68. The antibody or antigen-binding fragment thereof according to any one of claims 1 to 33, wherein the antibody or antigen-binding fragment thereof is an IgG1, IgG2, IgG3 or IgG4 molecule, or is derived from one of these.

69. The antigen binding fragment of any one of claims 1 to 68, wherein the antigen binding fragment is selected from the group consisting of: scFv, sc(Fv)2, dsFv, Fab, Fab', (Fab')2, and diabodies.

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

71. The antibody or antigen-binding fragment thereof of claim 70, wherein the Fc region comprises a modification.

72. The antibody or antigen binding fragment thereof of claim 71, wherein the antibody or antigen binding fragment thereof has increased binding to FcγR2B compared to a parent molecule lacking the Fc region modification.

73. The antibody or antigen binding fragment thereof of claim 71, wherein the antibody or antigen binding fragment thereof has increased binding to FcγR2B / FcγR2A compared to the parent molecule lacking the Fc region modification.

74. The antibody or antigen-binding fragment thereof of any one of claims 70 to 73, wherein the Fc region comprises one or more of the following amino acids: an alanine (A) at position 234, an alanine (A) at position 235, an aspartic acid (D) at position 236, an aspartic acid (D) at position 237, an aspartic acid (D) at position 238, an alanine (A) at position 265, a glutamic acid (E) at position 267, a glycine (G) at position 271, an arginine (R) at position 330, an alanine (A) at position 332, or an alanine (A) at position 297, all numbering according to the EU index.

75. The antibody or antigen-binding fragment thereof according to any one of claims 1 to 33, wherein the antibody is an IgG1 antibody.

76. The antibody or antigen-binding fragment thereof of claim 75, wherein the IgG1 antibody comprises one or more modifications at positions 234, 235, 236, 238, 239, 243, 250, 252, 254, 256, 257, 292, 297, 311, 322, 326, 329, 330, 332, 333, 396, 428, 433, and 434 (EU index).

77. The antibody or antigen-binding fragment thereof of claim 75, wherein the IgG1 antibody comprises one or more modifications selected from the group consisting of L234A, L235A, L235V, G236A, P238D, S239D, F243L, T250Q, M252Y, S254T, T256E, P257I, R292P, N297D, Q311, K322A, K326W, P329A, P329G, A330L, I332E, E333A, E333S, P396L, M428L, H433K, and N434F (EU index).

78. The antibody or antigen-binding fragment thereof of claim 75, wherein the IgG1 antibody comprises one or more modifications selected from the group consisting of: (a) S239D, A330L and I332E (EU Index); (b) L234A and L235A (EU Index); (c) T250Q and M428L (EU index); (d) M252Y, S254T, T256E, H433K and N434F (EU Index); (e) E333A (EU Index); (f) P257I and Q311 (EU index); (g) K326W and E333S (EU Index); (h) S239D, I332E and G236A (EU Index); (i) K322A (EU Index); and (j) P238D (EU Index).

79. The antibody or antigen-binding fragment thereof of claim 75, wherein the IgG1 antibody comprises a P238D substitution.

80. The antibody or antigen-binding fragment thereof according to any one of claims 1 to 33, wherein the antibody is an IgG2 antibody.

81. The antibody or antigen-binding fragment thereof of claim 80, wherein the IgG2 antibody is derived from a mouse IgG2 antibody.

82. The antibody or antigen-binding fragment thereof of claim 81, wherein the mouse IgG2 antibody comprises one or more modifications selected from the group consisting of L235E, E318A, K320A and K322A (EU index).

83. The antibody or antigen-binding fragment thereof of any one of claims 1 to 33, wherein the antibody is an IgG3 antibody.

84. The antibody or antigen-binding fragment thereof of any one of claims 1 to 33, wherein the antibody is an IgG4 antibody.

85. The antibody or antigen-binding fragment thereof of claim 84, wherein the IgG4 antibody comprises one or more modifications at positions 228, 234, 235, 327, 329, 330 and 331 (EU index).

86. The antibody or antigen-binding fragment thereof of claim 84, wherein the IgG4 antibody comprises one or more modifications selected from the group consisting of S228P, L234F, L235E, A327G, P329G, A330S and P331S (EU index).

87. The antibody or antigen-binding fragment thereof of claim 84, wherein the IgG4 antibody comprises a S228P substitution (EU index).

88. The antibody or antigen-binding fragment thereof according to any one of claims 1 to 87, wherein the antibody or antigen-binding fragment thereof binds to a region at or near the C-terminus of the extracellular portion of CD200R.

89. The antibody or antigen-binding fragment thereof according to any one of claims 1 to 88, wherein the antibody or antigen-binding fragment thereof binds to a region that is at most 50 amino acids, 45 amino acids, 40 amino acids, 35 amino acids, 30 amino acids, 25 amino acids, 20 amino acids or 15 amino acids from the C-terminus of the extracellular portion of CD200R.

90. The antibody or antigen binding fragment thereof according to any one of claims 1 to 89, wherein the antibody or antigen binding fragment thereof binds to a region that is about 50 amino acids, 45 amino acids, 40 amino acids, 35 amino acids, 30 amino acids, 25 amino acids, 20 amino acids, 18 amino acids, 16 amino acids, 15 amino acids, 14 amino acids, 13 amino acids, 12 amino acids, 10 amino acids, 8 amino acids, 6 amino acids or 5 amino acids from the C-terminus of the extracellular portion of CD200R.

91. The antibody or antigen binding fragment thereof according to any one of claims 1 to 90, wherein when the antibody or antigen binding fragment thereof binds to a CD200R molecule on a cell membrane, the antibody or antigen binding fragment thereof binds to a CD200R molecule at a distance of at most 100 μm from the cell membrane. or area.

92. The antibody or antigen-binding fragment thereof according to any one of claims 1 to 87, wherein the antibody or antigen-binding fragment thereof binds to a region near the N-terminus of CD200R.

93. The antibody or antigen-binding fragment thereof according to any one of the preceding claims, wherein the antibody or antigen-binding fragment thereof binds to a residue selected from T213, E230 and S194 of CD200R.

94. The antibody or antigen-binding fragment thereof according to any one of the preceding claims, wherein the antibody or antigen-binding fragment thereof binds to a residue selected from T213 and E230 of CD200R.

95. The antibody or antigen-binding fragment thereof according to any one of the preceding claims, wherein the antibody or antigen-binding fragment thereof does not bind to cynomolgus monkey CD200RLa, or binds to cynomolgus monkey CD200RLa with a K greater than 2 μM. D Binding to cynomolgus monkey CD200RLa as determined by surface plasmon resonance (SPR) at 37°C.

96. An antibody or antigen-binding fragment thereof that specifically binds to human CD200R or cynomolgus monkey CD200R, wherein the antibody or antigen-binding fragment thereof does not bind to cynomolgus monkey CD200RLa, or binds to cynomolgus monkey CD200RLa with a K of greater than 2 μM. D Binding to cynomolgus monkey CD200RLa as determined by surface plasmon resonance (SPR) at 37°C.

97. The antibody or antigen-binding fragment thereof of claim 96, wherein the antibody or antigen-binding fragment thereof binds to a residue selected from T213 and E230 of CD200R.

98. The antibody or antigen-binding fragment thereof of claim 94 or 97, wherein the antibody or antigen-binding fragment thereof binds to residues T213 and E230 of CD200R.

99. An antibody according to any of the preceding claims, wherein the antibody is: (a) a monoclonal antibody; (b) a human antibody or a humanized antibody; and / or (c) a chimeric antibody.

100. The antibody or antigen-binding fragment thereof according to any one of the preceding claims, wherein the antibody or antigen-binding fragment thereof agonizes CD200R expressed on the surface of an immune cell.

101. The antibody or antigen binding fragment thereof according to any of the preceding claims, wherein when bound to CD200R of an immune cell, the antibody or antigen binding fragment thereof reduces activation of the immune cell relative to an equivalent immune cell not bound by the antibody or antigen binding fragment thereof.

102. The antibody or antigen binding fragment thereof of any of the preceding claims, wherein when bound to CD200R of an immune cell, the antibody or antigen binding fragment thereof reduces proliferation of the immune cell relative to an equivalent immune cell not bound by the antibody or antigen binding fragment thereof.

103. The antibody or antigen-binding fragment thereof of claim 101 or 102, wherein the reduction in activation or proliferation of the immune cells is measured by the assay described in Example 5, Example 16 or Example 17.

104. The antibody or antigen-binding fragment thereof of claim 102, wherein the reduction in cell proliferation or activation is measured in vitro or in vivo.

105. The antibody or antigen-binding fragment thereof of any one of claims 102 to 104, wherein the reduction in cell proliferation or activation is at least about 10%, 15%, 20%, 25%, 30%, 40% or 50%.

106. The antibody or antigen-binding fragment thereof of any one of claims 102 to 104, wherein the reduction in cell proliferation or activation is about 10% to 50%, 10% to 40%, 10% to 30%, 10% to 20%, 10% to 15%, 20% to 50%, 20% to 40% or 20% to 30%.

107. The antibody or antigen binding fragment thereof of any of the preceding claims, wherein when bound to CD200R of an immune cell, the antibody or antigen binding fragment thereof reduces the expression of inflammatory genes in the immune cell relative to an equivalent immune cell not bound by the antibody or antigen binding fragment thereof.

108. The antibody or antigen binding fragment thereof according to any preceding claim, wherein binding of the antibody or antigen binding fragment thereof to CD200R expressed on the surface of an immune cell reduces NFκB signaling of the immune cell relative to an equivalent immune cell not bound by the antibody or antigen binding fragment thereof.

109. The antibody or antigen-binding fragment thereof of claim 108, wherein the reduction in NFKB signaling of the immune cells is measured by the assay described in Example 5.

110. The antibody or antigen binding fragment thereof of claim 108 or 109, wherein the reduction in NFKB signaling of the immune cell is at least about 10%, 15%, 20%, 25%, 30% or 40%.

111. The antibody or antigen-binding fragment thereof of claim 108 or 109, wherein the reduction in NFκB signaling of the immune cells is about 10% to 40%, 10% to 30%, 10% to 20%, 20% to 40%, or 30% to 40%.

112. The antibody or antigen-binding fragment thereof of claim 108 or 109, wherein the average maximum inhibition percentage of NFκB signaling of the immune cells induced by the antibody or antigen-binding fragment thereof is at least 20%, 30%, 40%, 50% or 60% higher than that of a control antibody, wherein the control antibody comprises: (a) a control heavy chain comprising CDRH1, CDRH2 and CDRH3 comprising the amino acid sequences shown in SEQ ID NOs: 55-57, respectively, and a control light chain comprising CDRL1, CDRL2 and CDRL3 comprising the amino acid sequences shown in SEQ ID NOs: 58-60, respectively; (b) a control heavy chain variable region comprising the amino acid sequence shown in SEQ ID NO:53, and a control light chain variable region comprising the amino acid sequence shown in SEQ ID NO:54; or (c) a control heavy chain sequence comprising the amino acid sequence shown in SEQ ID NO:73, and a control light chain sequence comprising the amino acid sequence shown in SEQ ID NO:

74.

113. The antibody or antigen-binding fragment thereof according to any one of claims 100 to 112, wherein the immune cell is a T cell or a monocyte.

114. An antibody or antigen-binding fragment thereof according to any preceding claim, wherein the antibody or antigen-binding fragment thereof inhibits activation of basophils.

115. The antibody or antigen-binding fragment thereof according to claim 114, wherein the antibody or antigen-binding fragment thereof inhibits activation of basophils induced by FcεRI.

116. The antibody or antigen-binding fragment thereof according to claim 114, wherein the antibody or antigen-binding fragment thereof inhibits activation of basophils induced by binding of IgE to the basophils.

117. The antibody or antigen-binding fragment thereof according to any one of claims 114 to 116, wherein the antibody or antigen-binding fragment thereof inhibits activation of basophils by at least 40% or at least 50%.

118. The antibody or antigen-binding fragment thereof of any one of claims 114 to 116, wherein the antibody or antigen-binding fragment thereof inhibits activation of basophils by about 10% to about 90%, about 20% to about 70%, about 30% to about 60%, or about 40% to about 60%.

119. The antibody or antigen-binding fragment thereof of any one of claims 114 to 116, wherein the antibody or antigen-binding fragment thereof inhibits activation of basophils by about 10%, 20%, 30%, 40%, 45%, 50%, 55%, 60%, 70%, 80% or 90%.

120. The antibody or antigen-binding fragment thereof of any one of claims 114 to 119, wherein the inhibition of basophil activation is measured in the assay described in Example 18.

121. The antibody or antigen-binding fragment thereof according to any one of the preceding claims, wherein the antibody or antigen-binding fragment thereof does not inhibit the binding of CD200 to CD200R.

122. The antibody or antigen-binding fragment thereof of any one of the preceding claims, wherein: (a) the antibody or antigen-binding fragment thereof has a K of less than 10 nM D Binding to human CD200R as determined by surface plasmon resonance (SPR) at 37°C; (b) the antibody or antigen-binding fragment thereof has a K of less than 5 nM D Binding to human CD200R as determined by surface plasmon resonance (SPR) at 37°C; (c) the antibody or antigen-binding fragment thereof has a K of less than 2 nM D Binding to human CD200R as determined by surface plasmon resonance (SPR) at 37°C; (d) the antibody or antigen-binding fragment thereof has a K of less than 1 nM D Binding to human CD200R as determined by surface plasmon resonance (SPR) at 37°C; (e) the antibody or antigen-binding fragment thereof has a K of less than 0.5 nM D Binding to human CD200R as determined by surface plasmon resonance (SPR) at 37°C; (f) the antibody or antigen-binding fragment thereof has a K of less than 100 nM D Binding to cynomolgus monkey CD200R as measured by surface plasmon resonance (SPR) at 37°C; (g) the antibody or antigen-binding fragment thereof has a K of less than 1 nM D Binding to cynomolgus monkey CD200R as measured by surface plasmon resonance (SPR) at 37°C; (h) the antibody or antigen-binding fragment thereof has a K of less than 0.1 nM D Binding to cynomolgus monkey CD200R as measured by surface plasmon resonance (SPR) at 37°C; or (i) The antibody or antigen-binding fragment thereof has a K of less than 0.01 nM D Binding to cynomolgus CD200R as determined by surface plasmon resonance (SPR) at 37°C.

123. The antibody or antigen binding fragment thereof according to any of the preceding claims, wherein the antibody or antigen binding fragment thereof does not induce significant cytokine release when the antibody or antigen binding fragment thereof binds to CD200R on the surface of an immune cell.

124. An antibody or antigen-binding fragment thereof according to any preceding claim, wherein the antibody or antigen-binding fragment thereof comprises a domain that binds to an Fc receptor.

125. The antibody or antigen-binding fragment thereof of claim 124, wherein the Fc receptor is expressed on the surface of an immune cell.

126. The antibody or antigen-binding fragment thereof of claim 125, wherein the immune cell is an antigen-presenting cell.

127. The antibody or antigen-binding fragment thereof of claim 126, wherein the antigen-presenting cell is a dendritic cell, a macrophage, a monocyte or a neutrophil.

128. The antibody or antigen binding fragment thereof according to any one of claims 125 to 127, wherein the binding of the antibody or antigen binding fragment thereof to the Fc receptor expressed on the surface of the immune cell and to CD200R on the surface of a second immune cell results in the cell surface of the immune cell and the cell surface of the second immune cell being expressed on the surface of the second immune cell. or Within.

129. The antibody or antigen-binding fragment thereof according to any one of claims 125 to 127, wherein the binding of the antibody or antigen-binding fragment thereof to the Fc receptor expressed on the surface of the immune cell and to CD200R on the surface of a second immune cell results in the cell surface of the immune cell and the cell surface of the second immune cell being covalently linked. or Within.

130. The antibody or antigen binding fragment thereof according to any one of claims 124 to 129, wherein the Fc receptor is FcγRIIB.

131. The antibody or antigen-binding fragment thereof according to any of the preceding claims, wherein the antibody or antigen-binding fragment thereof is bispecific or multispecific.

132. An isolated nucleic acid comprising one or more nucleotide sequences encoding a polypeptide capable of forming an antibody or antigen-binding fragment thereof according to any one of claims 1 to 131.

133. A vector comprising one or more nucleotide sequences encoding a polypeptide capable of forming an antibody or antigen-binding fragment thereof according to any one of claims 1 to 131.

134. A host cell comprising one or more nucleic acid molecules encoding the amino acid sequences of heavy and light chains, which when expressed are capable of forming an antibody or antigen-binding fragment thereof according to any one of claims 1 to 131.

135. A method comprising culturing the host cell of claim 134 under conditions whereby the antibody or antigen-binding fragment thereof is produced.

136. A method comprising: (a) providing a host cell, the host cell comprising one or more nucleic acid molecules encoding the amino acid sequences of the heavy chain and the light chain, wherein the one or more nucleic acid molecules are capable of forming the antibody or antigen-binding fragment thereof according to any one of claims 1 to 131 when expressed; (b) culturing the host cell expressing the encoded amino acid sequence; and (c) isolating the antibody or antigen-binding fragment thereof.

137. An immunoconjugate comprising the antibody or antigen-binding fragment thereof according to any one of claims 1 to 131 conjugated to an agent.

138. A pharmaceutical composition comprising a therapeutically effective amount of the antibody or antigen-binding fragment thereof according to any one of claims 1 to 131 or the immunoconjugate according to claim 137 and at least one pharmaceutically acceptable excipient.

139. An antibody or antigen-binding fragment thereof according to any one of claims 1 to 131 or an immunoconjugate according to claim 137 or a pharmaceutical composition according to claim 138 for use in therapy.

140. A kit comprising, in a container, the antibody or antigen-binding fragment thereof according to any one of claims 1 to 131, the immunoconjugate according to claim 137, or the pharmaceutical composition according to claim 138.

141. The kit of claim 140, further comprising informational material containing instructions for use of the antibody or antigen-binding fragment thereof according to any one of claims 1 to 131, the immunoconjugate according to claim 137, or the pharmaceutical composition according to claim 138.

142. A method for treating, preventing, alleviating or reducing the severity of a disease or condition in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of an antibody or antigen-binding fragment thereof according to any one of claims 1 to 131 or an immunoconjugate according to claim 137, or administering to the subject a pharmaceutical composition according to claim 138.

143. A method of treating, preventing, ameliorating or lessening the severity of a disease or condition in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of an antibody or antigen-binding fragment comprising a heavy chain variable region (HCVR) and a light chain variable region (LCVR), wherein: (a) the HCVR comprises a heavy chain complementary determining region 1 (CDRH1), CDRH2 and CDRH3, wherein CDRH1, CDRH2 and CDRH3 comprise the sequences of SEQ ID NOs: 3, 41 and 70, respectively, each having 0 to 3 amino acid modifications, such as 0, 1, 2 or 3 modifications; and the LCVR comprises a light chain complementary determining region 1 (CDRL1), CDRL2 and CDRL3, wherein CDRL1, CDRL2 and CDRL3 comprise the sequences of SEQ ID NOs: 6, 67 and 8, respectively, each having 0 to 3 amino acid modifications, such as 0, 1, 2 or 3 modifications; (b) the HCVR comprises a heavy chain complementary determining region 1 (CDRH1), CDRH2 and CDRH3, and wherein CDRH1, CDRH2 and CDRH3 comprise the sequences shown in SEQ ID NOs: 3, 41 and 5, respectively, each having 0 to 3 amino acid modifications, such as 0, 1, 2 or 3 modifications; and the LCVR comprises a light chain complementary determining region 1 (CDRL1), CDRL2 and CDRL3, and wherein CDRL1, CDRL2 and CDRL3 comprise the sequences shown in SEQ ID NOs: 6, 67 and 8, respectively, each having 0 to 3 amino acid modifications, such as 0, 1, 2 or 3 modifications; (c) the HCVR comprises a heavy chain complementary determining region 1 (CDRH1), CDRH2 and CDRH3, wherein CDRH1, CDRH2 and CDRH3 comprise the sequences set forth in SEQ ID NOs:92, 41 and 69, respectively; and the LCVR comprises a light chain complementary determining region 1 (CDRL1), CDRL2 and CDRL3, wherein CDRL1, CDRL2 and CDRL3 comprise the sequences set forth in SEQ ID NOs:6, 87 and 91, respectively; (d) the HCVR comprises an amino acid sequence that has at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence set forth in SEQ ID NO:72, and the LCVR comprises an amino acid sequence that has at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence set forth in SEQ ID NO:65; (e) the HCVR comprises the amino acid sequence as set forth in SEQ ID NO:72, having 0 to 10 amino acid modifications, such as 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid modifications, and the LCVR comprises the amino acid sequence as set forth in SEQ ID NO:65, having 0 to 10 amino acid modifications, such as 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid modifications; (f) the HCVR comprises an amino acid sequence that has at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence set forth in SEQ ID NO:71, and the LCVR comprises an amino acid sequence that has at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence set forth in SEQ ID NO:65; (g) the HCVR comprises the amino acid sequence as set forth in SEQ ID NO:71, having 0 to 10 amino acid modifications, such as 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid modifications, and the LCVR comprises the amino acid sequence as set forth in SEQ ID NO:65, having 0 to 10 amino acid modifications, such as 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid modifications; (h) the HCVR comprises an amino acid sequence that has at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence set forth in SEQ ID NO:93, and the LCVR comprises an amino acid sequence that has at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence set forth in SEQ ID NO:94; (i) the HCVR comprises the amino acid sequence as set forth in SEQ ID NO:93, having 0 to 10 amino acid modifications, such as 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid modifications, and the LCVR comprises the amino acid sequence as set forth in SEQ ID NO:94, having 0 to 10 amino acid modifications, such as 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid modifications; (j) the antibody or antigen-binding fragment thereof comprises: a heavy chain comprising an amino acid sequence having at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence shown in SEQ ID NO:82, and a light chain comprising an amino acid sequence having at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence shown in SEQ ID NO:86; (k) the antibody or antigen-binding fragment thereof comprises: a heavy chain comprising the amino acid sequence as shown in SEQ ID NO: 82, having 0 to 10 amino acid modifications, such as 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid modifications, and a light chain comprising the amino acid sequence as shown in SEQ ID NO: 86, having 0 to 10 amino acid modifications, such as 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid modifications; (l) the antibody or antigen-binding fragment thereof comprises: a heavy chain comprising an amino acid sequence having at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence shown in SEQ ID NO:83, and a light chain comprising an amino acid sequence having at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence shown in SEQ ID NO:86; (m) the antibody or antigen-binding fragment thereof comprises: a heavy chain comprising the amino acid sequence as shown in SEQ ID NO: 83, having 0 to 10 amino acid modifications, such as 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid modifications, and a light chain comprising the amino acid sequence as shown in SEQ ID NO: 86, having 0 to 10 amino acid modifications, such as 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid modifications; (n) the antibody or antigen-binding fragment thereof comprises: a heavy chain comprising an amino acid sequence having at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence shown in SEQ ID NO:84, and a light chain comprising an amino acid sequence having at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence shown in SEQ ID NO:86; (o) the antibody or antigen-binding fragment thereof comprises: a heavy chain comprising the amino acid sequence as shown in SEQ ID NO:84, having 0 to 10 amino acid modifications, such as 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid modifications, and a light chain comprising the amino acid sequence as shown in SEQ ID NO:86, having 0 to 10 amino acid modifications, such as 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid modifications; (p) the antibody or antigen-binding fragment thereof comprises: a heavy chain comprising an amino acid sequence having at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence shown in SEQ ID NO:85, and a light chain comprising an amino acid sequence having at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence shown in SEQ ID NO:86; (q) the antibody or antigen-binding fragment thereof comprises: a heavy chain comprising the amino acid sequence as shown in SEQ ID NO:85, having 0 to 10 amino acid modifications, such as 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid modifications, and a light chain comprising the amino acid sequence as shown in SEQ ID NO:86, having 0 to 10 amino acid modifications, such as 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid modifications; (r) the antibody or antigen-binding fragment thereof comprises: a heavy chain comprising an amino acid sequence having at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence as shown in SEQ ID NO:95, and a light chain comprising an amino acid sequence having at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence as shown in SEQ ID NO:98; (s) the antibody or antigen-binding fragment thereof comprises: a heavy chain comprising the amino acid sequence as shown in SEQ ID NO:95, having 0 to 10 amino acid modifications, such as 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid modifications, and a light chain comprising the amino acid sequence as shown in SEQ ID NO:98, having 0 to 10 amino acid modifications, such as 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid modifications; (t) the antibody or antigen-binding fragment thereof comprises: a heavy chain comprising an amino acid sequence having at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence shown in SEQ ID NO:96, and a light chain comprising an amino acid sequence having at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence shown in SEQ ID NO:98; (u) the antibody or antigen-binding fragment thereof comprises: a heavy chain comprising the amino acid sequence as shown in SEQ ID NO:96, having 0 to 10 amino acid modifications, such as 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid modifications, and a light chain comprising the amino acid sequence as shown in SEQ ID NO:98, having 0 to 10 amino acid modifications, such as 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid modifications; (v) the antibody or antigen-binding fragment thereof comprises: a heavy chain comprising an amino acid sequence having at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence shown in SEQ ID NO:97, and a light chain comprising an amino acid sequence having at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence shown in SEQ ID NO:98; or (w) the antibody or antigen-binding fragment thereof comprises: a heavy chain comprising the amino acid sequence as shown in SEQ ID NO:97, having 0 to 10 amino acid modifications, such as 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid modifications, and a light chain comprising the amino acid sequence as shown in SEQ ID NO:98, having 0 to 10 amino acid modifications, such as 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid modifications.

144. An antibody or antigen-binding fragment thereof that specifically binds to CD200R, the antibody or antigen-binding fragment thereof comprising (a) a heavy chain, wherein the heavy chain comprises a heavy chain variable region (HCVR) of SEQ ID NO: 72, and (b) a light chain, wherein the light chain comprises a light chain variable region (LCVR) of SEQ ID NO: 65, the antibody or antigen-binding fragment thereof being for use in treating a disease or condition.

145. An antibody or antigen-binding fragment thereof that specifically binds to CD200R, the antibody or antigen-binding fragment thereof comprising (a) a heavy chain, wherein the heavy chain comprises a heavy chain variable region (HCVR) of SEQ ID NO:71, and (b) a light chain, wherein the light chain comprises a light chain variable region (LCVR) of SEQ ID NO:65, the antibody or antigen-binding fragment thereof being for use in treating a disease or condition.

146. An antibody or antigen-binding fragment thereof that specifically binds to CD200R, the antibody or antigen-binding fragment thereof comprising (a) a heavy chain, wherein the heavy chain comprises a heavy chain variable region (HCVR) of SEQ ID NO: 93, and (b) a light chain, wherein the light chain comprises a light chain variable region (LCVR) of SEQ ID NO: 94, the antibody or antigen-binding fragment thereof being for use in treating a disease or condition.

147. An antibody or antigen-binding fragment thereof that specifically binds to CD200R, the antibody or antigen-binding fragment thereof comprising (a) a heavy chain of SEQ ID NO: 82 and (b) a light chain of SEQ ID NO: 86, the antibody or antigen-binding fragment thereof being used for use in treating a disease or condition.

148. An antibody or antigen-binding fragment thereof that specifically binds to CD200R, the antibody or antigen-binding fragment thereof comprising (a) a heavy chain of SEQ ID NO: 83 and (b) a light chain of SEQ ID NO: 86, the antibody or antigen-binding fragment thereof being used for use in treating a disease or condition.

149. An antibody or antigen-binding fragment thereof that specifically binds to CD200R, the antibody or antigen-binding fragment thereof comprising (a) a heavy chain of SEQ ID NO: 84 and (b) a light chain of SEQ ID NO: 86, the antibody or antigen-binding fragment thereof being used for use in treating a disease or condition.

150. An antibody or antigen-binding fragment thereof that specifically binds to CD200R, the antibody or antigen-binding fragment thereof comprising (a) a heavy chain of SEQ ID NO: 85 and (b) a light chain of SEQ ID NO: 86, the antibody or antigen-binding fragment thereof being used for use in treating a disease or condition.

151. An antibody or antigen-binding fragment thereof that specifically binds to CD200R, the antibody or antigen-binding fragment thereof comprising (a) a heavy chain of SEQ ID NO: 95 and (b) a light chain of SEQ ID NO: 98, the antibody or antigen-binding fragment thereof being used for use in treating a disease or condition.

152. An antibody or antigen-binding fragment thereof that specifically binds to CD200R, the antibody or antigen-binding fragment thereof comprising (a) a heavy chain of SEQ ID NO: 96 and (b) a light chain of SEQ ID NO: 98, the antibody or antigen-binding fragment thereof being used for use in treating a disease or condition.

153. An antibody or antigen-binding fragment thereof that specifically binds to CD200R, the antibody or antigen-binding fragment thereof comprising (a) a heavy chain of SEQ ID NO: 97 and (b) a light chain of SEQ ID NO: 98, the antibody or antigen-binding fragment thereof being used for use in treating a disease or condition.

154. The method of claim 142 or 143, wherein administering the antibody or antigen-binding fragment thereof comprises parenteral, intravenous, oral, subcutaneous, intraarterial, intracranial, intrathecal, intraperitoneal, intratumoral, topical, intranasal, or intramuscular administration.

155. The method of claim 142 or 143, wherein administering the antibody or antigen-binding fragment thereof comprises intravenous, subcutaneous, or intramuscular administration.

156. The antibody or antigen-binding fragment thereof of any one of claims 144 to 153, wherein the antibody or antigen-binding fragment thereof is administered via parenteral, intravenous, oral, subcutaneous, intraarterial, intracranial, intrathecal, intraperitoneal, intratumoral, topical, intranasal or intramuscular administration.

157. The antibody or antigen-binding fragment thereof according to any one of claims 144 to 153, wherein the antibody or antigen-binding fragment thereof is administered via intravenous, subcutaneous or intramuscular administration.

158. The method of any one of claims 142, 143, 154 and 155 or the antibody or antigen-binding fragment thereof of any one of claims 144 to 153, wherein the disease or disorder comprises a disease or disorder associated with CD200R activity or function.

159. The method of any one of claims 142, 143, 154 and 155 or the antibody or antigen-binding fragment thereof of any one of claims 144 to 153, wherein the disease or disorder comprises an autoimmune disease or disorder or an inflammatory disease or disorder.

160. The method or antibody or antigen-binding fragment thereof of claim 159, wherein the inflammatory disease or disorder is selected from the group consisting of a rheumatic disease or disorder, a gastrointestinal disease or disorder, a pulmonary disease or disorder, a hematological disease or disorder, a renal disease or disorder, and a skin disorder.

161. The method or antibody or antigen-binding fragment thereof of claim 160, wherein the inflammatory disease or condition is a rheumatic disease or condition selected from the group consisting of rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), lupus nephritis (LN), osteoarthritis (OA), Sjögren's syndrome, systemic sclerosis (SSc), ankylosing spondylitis (AS), dermatomyositis, psoriatic arthritis (PsA), ANCA vasculitis, IgG4-related disease, non-radiographic axial spondyloarthritis (nr-AxSpA), polymyositis, Takayasu arteritis, cutaneous lupus erythematosus (CLE) types: chronic CLE (including discoid), subacute CLE, acute CLE, seropositive or seronegative RA, juvenile idiopathic arthritis (JIA), primary OA or secondary OA, cervical and lumbar OA, hip OA, knee OA, and erosive OA.

162. The method or antibody or antigen-binding fragment thereof of claim 160, wherein the inflammatory disease or condition is a rheumatic disease or condition selected from rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), lupus nephritis (LN) and osteoarthritis (OA).

163. The method or antibody or antigen-binding fragment thereof of any one of claims 160 to 162, wherein the inflammatory disease or condition is a rheumatic disease or condition, and the rheumatic disease or condition is rheumatoid arthritis (RA).

164. The method or antibody or antigen-binding fragment thereof of claim 163, further comprising co-administering one or more additional therapeutic agents selected from the group consisting of disease-modifying antirheumatic drugs (DMARDs) such as hydroxychloroquine, sulfasalazine, methotrexate, and leflunomide; TNF inhibitors (e.g., etanercept, adalimumab, infliximab, golimumab, certolizumab pegol), T-cell co-stimulation inhibitors (e.g., abatacept), IL-6 receptor inhibitors (e.g., tocilizumab, salizumab), anti-CD20 antibodies (e.g., rituximab); and JAK inhibitors (e.g., tofacitinib, baricitinib, upadacitinib); NSAID , such as ibuprofen, naproxen, and diclofenac; COX-2 inhibitors, such as celecoxib and etoricoxib; steroids and corticosteroids, such as prednisolone and cortisone; and biologics known to be used to treat and / or prevent such conditions, including, for example, etanercept (e.g., ENBREL), infliximab (e.g., REMICADE), adalimumab (e.g., HUMIRA), anakinra (e.g., KINARET), abatacept (ORENCIA), rituximab (e.g., RITUXAN), certolizumab pegol (e.g., CIMZIA), golimumab (e.g., SIMPONI), and tocilizumab (e.g., ACTEMRA).

165. The method or antibody or antigen-binding fragment thereof of claim 163 or 164, further comprising co-administering two additional therapeutic agents, such as (a) methotrexate and leflunomide; (b) methotrexate and sulfasalazine; (c) methotrexate and cyclosporine; or (d) methotrexate and hydroxychloroquine.

166. The method or antibody or antigen-binding fragment thereof of claim 163 or 164, further comprising co-administering three additional therapeutic agents, such as (a) hydroxychloroquine, sulfasalazine, and methotrexate; or (b) hydroxychloroquine, sulfasalazine, and leflunomide.

167. The method or antibody or antigen-binding fragment thereof of any one of claims 160 to 162, wherein the inflammatory disease or condition is a rheumatic disease or condition, and the rheumatic disease or condition is systemic lupus erythematosus (SLE).

168. The method or antibody or antigen-binding fragment thereof of claim 167, further comprising co-administering one or more additional therapeutic agents selected from the group consisting of hydroxychloroquine, steroids and corticosteroids (e.g., prednisone, methylprednisolone), belimumab, azathioprine, methotrexate, cyclophosphamide, mycophenolate mofetil and mycophenolate mofetil, cyclosporine, leflunomide, voriconazole, abatacept, anirumab, rituximab, NSAIDS such as naproxen sodium and ibuprofen, antimalarials such as hydroxychloroquine, calcineurin inhibitors, and tacrolimus.

169. The method or antibody or antigen-binding fragment thereof of any one of claims 160 to 162, wherein the inflammatory disease or condition is a rheumatic disease or condition, and the rheumatic disease or condition is lupus nephritis (LN).

170. The method or antibody or antigen-binding fragment thereof of claim 169, further comprising co-administering one or more additional therapeutic agents selected from the group consisting of azathioprine, belimumab, cyclophosphamide, cyclosporine, mycophenolic acid analogs, mizoribine, mycophenolate sodium, prednisone, rituximab, tacrolimus, and voriconazole.

171. The method or antibody or antigen-binding fragment thereof of claim 169, further comprising co-administering two additional therapeutic agents, such as (a) prednisone and mycophenolic acid analogs; (b) prednisone and mycophenolate sodium; (c) prednisone and cyclophosphamide; (d) prednisone and tacrolimus; (e) prednisone and cyclosporine; (f) prednisone and rituximab; (g) prednisone and azathioprine; (h) prednisone and cyclosporine; or (i) prednisone and mizoribine.

172. The method or antibody or antigen-binding fragment thereof of claim 169, further comprising co-administering three additional therapeutic agents, such as (a) prednisone, belimumab, and a mycophenolic acid analog; or (b) prednisone, belimumab, and cyclophosphamide.

173. The method or antibody or antigen binding fragment thereof of any one of claims 160 to 162, wherein the inflammatory disease or condition is a rheumatic disease or condition, and the rheumatic disease or condition is osteoarthritis.

174. The method or antibody or antigen-binding fragment thereof of claim 167, further comprising co-administering one or more additional therapeutic agents selected from the group consisting of nonsteroidal anti-inflammatory drugs (NSAIDs), topical capsaicin, intra-articular glucocorticoid injections, acetaminophen, duloxetine, tramadol, and injectable corticosteroids such as methylprednisolone acetate, triamcinolone acetonide acetate, betamethasone acetate and betamethasone sodium phosphate, triamcinolone acetonide hexane, and dexamethasone.

175. The method or antibody or antigen-binding fragment thereof of claim 160, wherein the inflammatory disease or condition is a gastrointestinal disease or condition selected from the group consisting of ulcerative colitis (UC), Crohn's disease (CD), eosinophilic gastroenteropathy (EGID), microscopic colitis, ulcerative proctitis, proctosigmoiditis, left-sided colitis, extensive colitis, pancolitis, ileocolitis, ileitis, gastroduodenal CD, jejunoileitis, and Crohn's (granulomatous) colitis.

176. The method or antibody or antigen-binding fragment thereof of claim 160 or 175, wherein the inflammatory disease or condition is a gastrointestinal disease or condition selected from ulcerative colitis (UC) and Crohn's disease (CD).

177. The method or antibody or antigen-binding fragment thereof of claim 176, further comprising co-administering one or more additional therapeutic agents selected from the group consisting of infliximab, adalimumab, golimumab, vedolizumab, tofacitinib, ustekinumab, natalizumab, aminosalicylic acid, azo-bonded 5-ASA, sulfasalazine, balsalazide, olsalazine, corticosteroids such as budesonide, hydrocortisone, methylprednisolone and prednisone; immunosuppressants or immunomodulators such as azathioprine and 6-mercaptopurine, cyclosporine and methotrexate.

178. The method or antibody or antigen-binding fragment thereof of claim 160, wherein the inflammatory disease or condition is a pulmonary disease or condition selected from the group consisting of idiopathic pulmonary fibrosis (IPF), interstitial lung disease (ILD), acute respiratory distress syndrome (ARDS), asthma, bronchiolitis obliterans, chronic obstructive pulmonary disease (COPD), connective tissue disease-associated interstitial lung disease (CTD-ILD), collagen vascular disease, pulmonary alveolar proteinosis, hypersensitivity pneumonitis (HP), non-cystic fibrosis bronchiectasis (non-CFB), cystic fibrosis, bronchiectasis, primary ciliary dyskinesia, pneumonitis pulmonary hypertension (PAH), lymphangioleiomyomatosis, nonspecific interstitial pneumonia, cryptogenic organizing pneumonia, acute interstitial pneumonia, familial interstitial lung disease, and bleomycin-induced pulmonary fibrosis.

179. The method or antibody or antigen-binding fragment thereof of claim 178, wherein the inflammatory disease or disorder is a pulmonary disease or disorder selected from idiopathic pulmonary fibrosis (IPF) and interstitial lung disease (ILD).

180. The method or antibody or antigen-binding fragment thereof of claim 178 or 179, further comprising co-administering one or more additional therapeutic agents selected from the group consisting of nintedanib, pirfenidone, corticosteroids such as prednisone, other rheumatic drugs including mycophenolate mofetil (e.g., ), azathioprine (e.g. ), leflunomide (e.g., ), rituximab (e.g., ), cyclophosphamide (e.g., ), tacrolimus (e.g., ), drugs that reduce gastric acid such as H-2-receptor antagonists or proton pump inhibitors such as lansoprazole (e.g., 24HR), omeprazole (e.g., Prilosec OTC), and pantoprazole (e.g., ).

181. The method or antibody or antigen-binding fragment thereof of claim 160, wherein the inflammatory disease or disorder is a hematological disease or disorder selected from the group consisting of non-alcoholic steatohepatitis (NASH), primary sclerosing cholangitis (PSC), primary biliary cirrhosis (PBC), autoimmune hepatitis, alcoholic steatohepatitis (ASH), alcoholic hepatitis, chronic intrahepatic or extrahepatic cholestasis, obstructive or chronic inflammatory diseases of the liver, liver fibrosis, cirrhosis, liver steatosis, liver ischemia, chemotherapy-associated steatohepatitis (CASH), lipid and lipoprotein diseases, type II diabetes, type I diabetes, non-alcoholic fatty liver disease (NAFLD) and Barrett's esophagus.

182. The method or antibody or antigen-binding fragment thereof of claim 160, wherein the inflammatory disease or disorder is a hematological disease or disorder selected from non-alcoholic steatohepatitis (NASH) and non-alcoholic fatty liver disease (NAFLD).

183. The method or antibody or antigen-binding fragment thereof of claim 160, wherein the inflammatory disease or disorder is a kidney disease or disorder selected from the group consisting of diabetic kidney disease (DKD) (diabetic nephropathy), chronic kidney disease (CKD), kidney disease, renal fibrosis, renal insufficiency, acute kidney injury, tubular dysfunction, 2,8-dihydroxyadenine nephropathy, renal transplant rejection, renal protection against drugs that induce Fanconi syndrome, hereditary fructose intolerance, metabolic syndrome, obesity, hyperlipidemia, hypertriglyceridemia, hypertension, steatosis, cardiometabolic syndrome, insulin resistance, cardiovascular disease, heart failure, type 1 diabetes, type 2 diabetes, and hyperuricemia.

184. The method or antibody or antigen-binding fragment thereof of claim 160, wherein the inflammatory disease or disorder is a kidney disease or disorder selected from diabetic kidney disease (DKD) (diabetic nephropathy) and chronic kidney disease (CKD).

185. according to any one of the methods or antibodies or antigen-binding fragments thereof of claims 181 to 184, the method further comprising co-administering one or more additional therapeutic agents selected from the group consisting of metformin, sodium-glucose co-transporter-2 inhibitors (SGLT2i), drug therapy for glycemic control, DPP-4 inhibitors, insulin, sulfonylureas, TZDs (thiazolidinediones), alpha-glucosidase inhibitors, SGLT2 inhibitors (e.g., empagliflozin, canagliflozin, dapagliflozin), glucagon-like peptide-1 receptor agonists (GLP-1RA) (e.g., For example, lixisenatide, liraglutide, semaglutide, exenatide, albiglutide, dulaglutide), DPP-4 inhibitors (e.g., saxagliptin, alogliptin, sitagliptin, linagliptin), one or more agents for treating high blood pressure (such as angiotensin converting enzyme (ACE) inhibitors and angiotensin 2 receptor blockers (ARBs)), agents to support weight loss or for controlling blood sugar, cholesterol-lowering drugs (e.g., statins), finerenone, and agents for treating diabetes, such as alpha-glucosidase inhibitors (e.g., acarbose, miglitol, voglibose).

186. The method or antibody or antigen-binding fragment thereof of claim 160, wherein the inflammatory disease or condition is a skin condition selected from atopic dermatitis (AD), contact dermatitis, dyshidrotic eczema, seborrheic dermatitis, neurodermatitis, nummular eczema, stasis dermatitis, hand eczema, vitiligo, alopecia areata, acne, psoriasis, dermatomyositis, scleroderma, and morphea.

187. The method or antibody or antigen-binding fragment thereof of claim 160, wherein the inflammatory disease or disorder is the skin disorder of atopic dermatitis.

188. The method or antibody or antigen-binding fragment thereof of claim 186 or 187, further comprising co-administering one or more additional therapeutic agents selected from the group consisting of topical corticosteroids (TCS) (e.g., desonide, hydrocortisone, fluocinolone, triamcinolone, betamethasone dipropionate), topical calcineurin inhibitors (TCI) (e.g., tacrolimus, pimecrolimus), topical antimicrobials and preservatives, cyclosporine, methotrexate, mycophenolate mofetil, interferon gamma, phosphodiesterase 4 (PDE4) inhibitors such as crisaborole, JAK inhibitors (e.g., ruxolitinib, upadacitinib, abrocitinib), systemic glucocorticoids (e.g., prednisone), dupilumab, and anti-IL-13 antibodies (e.g., trorocitumab).

189. The method or antibody or antigen-binding fragment thereof of claim 186 or 187, wherein the disease or condition comprises a skin disease or condition and the method further comprises administering to the subject one or more additional therapeutic agents selected from antihistamines, corticosteroids, calcineurin inhibitors, antibiotics, and phototherapy.

190. The method or antibody or antigen-binding fragment thereof of claim 189, wherein the antihistamine is selected from the group consisting of diphenhydramine, cetirizine, desloratadine, fexofenadine, levocetirizine, and loratadine.

191. The method or antibody or antigen-binding fragment thereof of claim 189, wherein the corticosteroid is selected from the group consisting of cortisone, hydrocortisone and prednisone.

192. The method or antibody or antigen-binding fragment thereof of claim 189 or 191, wherein the corticosteroid is administered as a cream, ointment or orally.

193. The method or antibody or antigen-binding fragment thereof of claim 189, wherein the calcineurin inhibitor is selected from the group consisting of Astagraf XL, Cequa, cyclosporine, cyclosporine ophthalmic, Elidel, Envarsus XR, Gengraf, Hecoria, Lupkynis, Neoral, Pimecrolimus, Prograf, Protopic, Restasis, Sandimin, Tacrolimus, Tacrolimus ointment, Verkazia, and Vorbisporin.

194. The method or antibody or antigen-binding fragment thereof of claim 189, wherein the antibiotic is selected from the group consisting of vancomycin, ceftaroline, daptomycin, doxycycline, linezolid, telavancin, tigecycline, and trimethoprim-sulfamethoxazole.

195. The method or antibody or antigen-binding fragment thereof of any one of claims 142 to 159, wherein the disease or disorder comprises an autoimmune skin disease or disorder.

196. The method or antibody or antigen-binding fragment thereof of claim 195, wherein the autoimmune skin disease or disorder comprises Behcet's disease, dermatitis herpetiformis, dermatomyositis, epidermolysis bullosa, lichen planus, linear IgA disease, cutaneous lupus, morphea / scleroderma, ocular cicatricial pemphigoid, pemphigoid, bullous pemphigoid, pemphigus, psoriasis, scleroderma, or vasculitis.

197. The method of any one of claims 142 to 196, further comprising administering to the subject 1, 2, 3, 4 or more additional therapeutic agents.

198. The method of claim 197, wherein the one or more additional therapeutic agents are selected from the group consisting of 5-HT 1a receptor partial agonists and antagonists, 5-HT 2a receptor partial agonists and antagonists, 5-HT 2b receptor antagonists, 5-HT 6 receptor antagonists, 5-HT 7 receptor antagonists, Abl tyrosine kinase inhibitors, ACE inhibitors, acid mammalian chitinase inhibitors, actin antagonists, acetaldehyde dehydrogenase inhibitors, acetyl CoA carboxylase (ACC) inhibitors, ACC-1 inhibitors, ACC-2 inhibitors, 2-acylglycerol 0-acyltransferase 2 (DGAT2) inhibitors, ACTH receptor agonists, activin receptor antagonists, adenosine homocysteinease-1 inhibitors, adenosine receptor antagonists and agonists, adenosine deaminase inhibitors, adenylate cyclase-related protein 1 inhibitors, lipotrophin inhibitors, adiponectin receptor agonists, ADP ribosyl cyclase-1 inhibitors, ADP ribosyl cyclase-1 modulators, ADP ribosylation factor 6 inhibitors, adrenocorticotropic hormone ligands, adrenomedullin ligands, adrenergic receptor antagonists and agonists, energy balance-related protein stimulators, polyprotein Glucosyltransferase-2 inhibitors, AIMP multisynthase complex protein 1 stimulators, AKT1 gene inhibitors, AKT protein kinase inhibitors, albumin antagonists, albumin modulators, aldehyde dehydrogenase 2 stimulators, aldosterone antagonists, aldosterone synthase inhibitors, Alk-5 protein kinase inhibitors, α2 adrenergic receptor agonists, α2 adrenergic receptor modulators, α1 antitrypsin stimulators, α-fetoprotein modulators, Alstrom syndrome protein 1 (ALMS1) / PKCα protein interaction inhibitors, 1-aminocyclopropane carboxyl synthase inhibitors, pullulan receptor agonists, AMP-activated protein kinase (AMPK), AMP-activated protein kinase inhibitors, activators or stimulators, AMP-activated protein kinase α2 stimulators, androgen receptor agonists and antagonists, angiopoietin-related protein-3 inhibitors, angiotensin II receptor antagonists, angiotensin II AT-1 receptor antagonists, angiotensin IIAT-2 receptor agonists, angiotensinogen ligand inhibitors, annexin A1 modulators, antibiotics, antifungal agents, anti-IL6 antibodies, anti-TNF steroid conjugates, activator protein 1 (AP1) transcription factor inhibitors, AP1 transcription factor regulators, apelin receptor agonists, APOA1 gene stimulators, apolipoprotein A antagonists, apolipoprotein B regulators, apolipoprotein L1 regulators, apoptosis regulator Bcl w inhibitors, aryl hydrocarbon receptor (AHR) agonists and modulators, AHR agonists plus autoantigens, ASK1 inhibitors, ATPase inhibitors, ATP binding cassette transporter C2 inhibitors, ATP citrate lyase inhibitors, autophagy protein regulators and stimulators, autotoxin inhibitors, Axl tyrosine kinase receptor inhibitors, BAFF / APRIL inhibitors,Basic glycoprotein inhibitors, B and T lymphocyte attenuation stimulators, Bax protein stimulators, Bcl-2 protein inhibitors, Bcl-xLBcl-2-related death promoter inhibitors, Bcl-xL Bcl-2-related death promoter modulators, Bcr protein inhibitors, benzodiazepine receptor agonists, beta adrenergic receptor antagonists, BET inhibitors, beta2 adrenergic receptor agonists, beta amyloid antagonists, beta-catenin inhibitors, beta-catenin modulators, beta-catenin stimulators, beta-galactosidase inhibitors, beta-lactamase modulators, 17beta-hydroxysteroid dehydrogenase 13 inhibitors, bifunctional aminoacyl tRNA synthetase inhibitors, B-lymphocyte antigen CD19 inhibitors, B-lymphocyte antigen CD20 inhibitors, B-lymphocyte antigen CD20 modulators, B-lymphocyte adhesion molecule inhibitors, B-lymphocyte B-lymphocyte stimulating ligand inhibitors, B-lymphocyte stimulating ligand modulators, bioactive lipids, bone morphogenetic protein-7 ligand, bone morphogenetic protein-7 ligand modulators, bradykinin receptor modulators, BRAF gene inhibitors, branched-chain amino acid aminotransferase 1 inhibitors, bromodomain domain-containing protein (BRD) inhibitors, BRD1, BRD2 and BRD4 inhibitors, BTK inhibitors, B7 homologous inhibitors, cadherin-11 antagonists, Cak tyrosine kinase receptor inhibitors, calcineurin inhibitors, calcium channel inhibitors, Ca2+ release-activated Ca2+ channel 1 inhibitors, calcitonin agonists, calpain-IX inhibitors, calpain-I inhibitors preparations, calpain-II inhibitors, calreticulin inhibitors, caveolin-1 stimulators, cannabinoid CB1 receptor antagonists and inverse agonists, cannabinoid CB2 receptor agonists, cannabinoid receptor antagonists and agonists, cannabinoid CB1 receptor inverse agonists, carbohydrate metabolism modulators, carbonic anhydrase inhibitors, casein kinase-Iδ and / orε inhibitors, CASP9 gene stimulators, caspase inhibitors, caspase-3 stimulators, catalase stimulators, cathepsin inhibitors, cathepsin K inhibitors, cathepsin S inhibitors, caveolin-1 inhibitors, CCK receptor antagonists, CCAAT enhancer binding protein β modulators, CC Motif ligand 26 (CCL26) gene inhibitors, chemokine receptor antagonists, CC motif chemokine receptor (CCR) 1 antagonists, CCR2 antagonists, CCR3 antagonists and modulators, CCR4 antagonists, CCR5 antagonists, CCR6 antagonists, CCR7 modulators, CCR9 chemokine antagonists, CCR3 gene modulators, CD3 modulators or antagonists, CD4 agonists or antagonists, CD7 inhibitors, CD11b agonists, CD29 modulators, CD39 agonists, CD40 ligand receptor modulators or antagonists, CD47 antagonists, CD52 antagonists, CD73 agonists and antagonists, CD79b modulators,CD80 modulators or antagonists, CD86 modulators or antagonists, CD95 antagonists, CD126 antagonists, CD223 modulators, CDGSH iron-sulfur domain protein modulators, CDw123 antagonists, cell adhesion molecule inhibitors, cell surface glycoprotein CD200R agonists, cell surface glycoprotein MUC18 inhibitors, chemokine CXC ligand inhibitors, chaperone protein inhibitors and modulators, chitinase inhibitors, chitotriosidase 1 inhibitors, chloride channel stimulators, cholera enterotoxin subunit B inhibitors, choline kinase inhibitors, CHST15 gene inhibitors, chymotrypsin inhibitors, tight junction protein 1 inhibitors, clusterin stimulators, CNR1 inhibitors, collagen I antagonists, collagen VII antagonists, collagen gene inhibitors, collagenase inhibitors, collagen modulators, complement C1q subcomponent inhibitors, complement C1s subcomponent inhibitors, complement C3 inhibitors, complement C5 factor inhibitors, complement C5a receptor antagonists, complement cascade inhibition agonists, complement factor stimulators, complement factor B inhibitors, complement factor D inhibitors, connective tissue growth factor ligand inhibitors, corticosteroid hormone receptor agonists, COT protein kinase inhibitors, CREB binding protein inhibitors, C-reactive protein (CRP) inhibitors, cerebrospinal fluid (CSF)-1 agonists and antagonists, C-type lectin domain protein 4C inhibitors, CTGF gene inhibitors, CX3CR1 antagonists and modulators, CXCR2 antagonists, CXCR3 antagonists, CXCR4 antagonists and modulators, CXCR5 antagonists and modulators, CXC5 ligand inhibitors, CXC6 chemokine ligand inhibitors, CXC10 ligand inhibitors, CXC11 ligand modulators, cyclin-dependent kinase (CDK) 1, 2, 5, 7 and / or 9 inhibitors, cyclooxygenase (COX) inhibitors, COX-1 inhibitors, COX-2 inhibitors and modulators, cysteine ​​palmitoyltransferase porcupine inhibitors, cytochrome P450 7A1 inhibitors, cytochrome P45011B2 inhibitors, cytochrome P450 2E1 inhibitors (CYP2E1), cytochrome P450 reductase inhibitors, cytokine receptor agonists and antagonists, cytosolic phospholipase A2 (cPLA2) inhibitors, cytotoxic T lymphocyte protein-4 (CTLA4) modulators and stimulators, deoxyribonuclease (DNase) modulators, DNase γ stimulators, DNase I stimulators, DGAT2 gene inhibitors, DHFR inhibitors, diacylglycerol O acyltransferase (DGAT) 1 inhibitors, DGAT2 inhibitors, diamine acetyltransferase inhibitors, dihydroceramide δ4 desaturase inhibitors, dihydroorotate dehydrogenase inhibitors, dipeptidyl peptidase (DPP) I inhibitors, DPP IV inhibitors, DNA binding protein Ikaros inhibitors, DNA methyltransferase inhibitors, DNA polymerase inhibitors, dopamine D2 receptor partial agonists, dopamine D3 receptor partial agonists,Dopamine D4 receptor partial agonists, dopamine D2 receptor agonists, DYRK-1α protein kinase inhibitors, ectonucleotide pyrophosphatase-PDE-2 inhibitors, EGFR tyrosine kinase receptor inhibitors, EGR1 gene inhibitors, elongation factor 2 inhibitors, endoglin inhibitors, endosialin inhibitors, endosialin modulators, endostatin modulators, endothelin ET-A receptor antagonists, endothelin ET-B receptor antagonists, endothelial nitric oxide synthase stimulators, enolase 1 inhibitors, enteropeptidase inhibitors, eotaxin 2 ligand inhibitors, eotaxin ligand inhibitors, EP4 prostanoid receptor antagonists or agonists, EP4 prostanoid receptor antagonists, epidermal growth factor (EGF) receptor antagonists, EGF modulators, epoxide hydrolase inhibitors, erythropoietin receptor antagonists or agonists, exportin 1 inhibitors, extracellular matrix protein modulators, F1F0 ATP synthase modulators, facilitative glucose transporter-1 modulators, factor IIa antagonists, factor XIIa antagonists, farnesoid X receptor (FXR) agonists and modulators, fatty acid synthase inhibitors, fecal microbiota transplantation (FMT), fibroblast activation protein (FAP) inhibitors, fibroblast growth factor (FGF) receptor agonists and antagonists, FGF-2 ligand inhibitors, FGF1 receptor agonists and antagonists, FGF2 receptor antagonists, FGF3 receptor antagonists, FGF19 gene stimulators, FGF-15 ligands or modulators, FGF-19 ligands or modulators, FGF-21 ligands or modulators, FK506 binding protein inhibitors, FK506 binding protein -10 inhibitor, FK506 binding protein-12 modulator, Flt3 tyrosine kinase inhibitor, focal adhesion kinase inhibitor, folate antagonist or agonist, folate receptor beta antagonist, FP prostanoid receptor antagonist, Fractalkine ligand inhibitor, free fatty acid receptor 1, 2 and / or 3 agonist, free fatty acid receptor 2 antagonist, Frizzled-5 receptor agonist, Frizzled-8 receptor agonist, Fyn tyrosine kinase inhibitor, G protein-coupled bile acid receptor 1 agonist, G protein-coupled receptor 15 antagonist, G protein beta subunit inhibitor, G protein-coupled receptor (GPCR) 35, 44, 84, 119, 120 modulator, GPCR 44, 87 antagonists, GABA A receptor modulators, GABA A receptor α-2 subunit modulators, GABA A receptor α-3 subunit modulators, galanin GAL2 receptor agonists, galectin-3 inhibitors, gastric inhibitory polypeptide receptor (GIP-R) agonists and modulators, GATA 3 transcription factor inhibitors, GDNF family receptor α-like agonists, GHR gene inhibitors, glucagon-like peptide (GLP) 1 agonists, GLP 2 agonists, GLP 1 receptor modulators, glucocorticoid agonists or antagonists,Glucocorticoid-induced leucine zipper stimulators, glucokinase stimulators, glucose 6-phosphate 1 dehydrogenase inhibitors, glutaminyl peptide cyclotransferase inhibitors, glutaredoxin 1 modulators, glutathione-dependent PGD synthase inhibitors, glycoprotein Ib (GPIb) antagonists, GM-CSF receptor antagonists or modulators, GMP synthase inhibitors, GNRH receptor modulators, GP IIb IIIa antagonist, GPCR modulator, GPR40 agonist, GPR84 antagonist, GroEL protein 2 inhibitor, GroEL protein 2 inhibitor, growth hormone ligand, growth hormone receptor agonist, somatomedin α ligand inhibitor, guanylate cyclase receptor agonist, guanylate cyclase stimulator, heat shock protein inhibitor, H+K+ ATPase inhibitor, hedgehog (Hh) regulator, Hh protein inhibitor, heme oxygenase 1 regulator, hepatitis B structural protein inhibitor, hepatitis C virus NS3 protease inhibitor, hepatitis C virus protein NS5A inhibitor, hepatocyte nuclear factor 4α Regulators (HNF4A), hepatocyte growth factor regulators and antagonists, hypoxia-inducible factor (HIF) prolyl hydroxylase inhibitors, HIF prolyl hydroxylase-2 inhibitors, high mobility group protein B1 inhibitors, histamine H1 receptor antagonists, histamine H4 receptor agonists, histamine H4 receptor antagonists, histamine H4 receptor modulators, histone deacetylase (HDAC) inhibitors, HDAC-1 inhibitors, HDAC-2 inhibitors, HDAC-3 inhibitors, HDAC-6 inhibitors, H+K+ ATPase inhibitors, HIV-1gp120 protein inhibitors, HLA antigen modulators, HLA Class II antigen DQ-2α modulators, HLA class II antigen DR-1β inhibitors, HLA class II antigen inhibitors, HLA class II antigen modulators, HMG CoA reductase inhibitors, homeodomain interacting kinase 2 (HIPK2) inhibitors, hormone-sensitive lipase stimulators, HSD17B3 gene modulators, HSD17B13 gene inhibitors, Hsp 70 family inhibitors and stimulators, Hsp 90 inhibitors, hyaluronidase stimulators, hydrolase inhibitors, hypoxia inducible factor (HIF) regulators, HIF-1 inhibitors, HIF-1α regulators and stimulators, HIF-2α inhibitors, ICAM1 gene inhibitors, ICE inhibitors, interferon β (IFNB) gene stimulators, insulin-like growth factor 1 (IGF1) gene inhibitors, IgG receptor FcRn large subunit p51 antagonists, IgG receptor FcRn large subunit p51 regulators, I-κB kinase inhibitors, I-κB kinase β inhibitors, IK potassium channel inhibitors, interleukin (IL) -1 antagonists, IL-2 agonists or antagonists, IL-3 antagonists, IL-4 agonists or antagonists, IL-5 antagonists, IL-6 agonists or antagonists, IL-7 receptor antagonists, IL-8 antagonists,10 antagonists or agonists, IL-11 agonists, IL-12 antagonists, IL-13 antagonists, IL-15 antagonists, IL-17, IL17A and IL17B agonists or antagonists, IL-18 antagonists, IL-21 antagonists, IL-22 agonists or antagonists, IL-23 antagonists, IL-1β ligand modulators, IL-23A inhibitors, IL-31 receptor modulators and antagonists, IL-36 inhibitors, IL-6 neutralizing human antibodies, IL-1 receptor adjuvants Protein inhibitors, IL-18 receptor accessory protein antagonists, IL-2 receptor α subunit inhibitors, IL-2 receptor α subunit stimulators, interleukin ligands, IL-1α ligand inhibitors, IL-1 ligand inhibitors, IL-1β ligand inhibitors and modulators, IL-1β ligands, interleukin ligand inhibitors, IL-2 ligands, IL-4 ligands, IL-4 ligand inhibitors, IL-6 ligand inhibitors, IL-8 ligand inhibitors, IL-10 ligands, IL-13 ligand inhibitors, IL 17 ligand inhibitors, IL 17A ligand inhibitors and modulators, IL-17F ligand inhibitors, IL 18 ligand inhibitors, interleukin-22 ligands, IL-29 ligands, IL-33 ligand inhibitors, IL-1-like receptor inhibitors, ileal bile acid sodium cotransporter inhibitors, immunoglobulin (Ig) agonists or antagonists, IgE antagonists and modulators, immunoglobulin Fc receptor modulators, IgG agonists, IgG1 agonists and antagonists, IgG2 antagonists and modulators, immunoglobulin gamma Fc receptor antagonists, immunoglobulin gamma Fc receptor II modulators, immunoglobulin gamma Fc receptor IIB antagonists, immunoglobulin kappa modulators, immunoglobulin-like domain receptor 2 antagonists, IgM antagonists, inducible nitric oxide synthase inhibitors (iNOS inhibitors), inducible T cell co-stimulator inhibitors, inosine monophosphate dehydrogenase inhibitors, insulin ligands, insulin ligand agonists, insulin receptor agonists, insulin receptor substrate-1 inhibitors, insulin sensitizers, integrin antagonists and modulators, integrin α-1 / β-1 antagonists, integrin α-4 / β-1 antagonists, integrin α-V / β-1 antagonists, integrin α-V / β-3 antagonists, integrin α-V / β-6 antagonists, integrin α-V / β-8 modulators, integrin α-4 / β-7 antagonists, integrin α-9 antagonists, interferon (IFN) α ligands, IFNα ligand inhibitors and modulators, IFNω ligand inhibitors, IFNβ ligands, IFNβ ligand inhibitors, IFNγ ligands, IFNγ receptor 1 agonists, IFNγ receptor antagonists, IFN Type I receptor antagonists, interleukin-1 receptor associated kinase 4 (IRAK4) inhibitors, IRE1 protein kinase inhibitors, Itk tyrosine kinase inhibitors, Janus kinase (JAK) inhibitors and modulators, JAK3 gene inhibitors,JAK1 inhibitors, JAK2 inhibitors, JAK3 inhibitors, Jun N-terminal kinase inhibitors, Jun N-terminal kinase-1 inhibitors, kallikrein inhibitors, kallikrein 2 inhibitors, kallikrein 7 inhibitors, KCNA voltage-gated potassium channel 3 inhibitors, KCNA voltage-gated potassium channel 3 modulators, KCNN potassium channel 4 inhibitors, KCNN4 gene inhibitors, Kelch-like ECH-related protein 1 modulators, hexokinases (KHK) inhibitors, Kit tyrosine kinase inhibitors, Klothoβ stimulators, lactoferrin stimulators, LanC-like protein 2 stimulators, LanC-like protein 2 modulators, Lck tyrosine kinase inhibitors, LDHA gene inhibitors, LDL receptor-associated protein 1 stimulators, LDL receptor-associated protein 6 inhibitors, LDL receptor-associated protein 6 stimulators, lectin mannose binding protein inhibitors, leukocyte elastase inhibitors, leukocyte Ig-like Receptor A4 modulators, leukocyte proteinase 3 inhibitors, leukotriene receptor antagonists, leukotriene A4 hydrolase inhibitors, leukotriene BLT receptor antagonists, leukotriene D4 antagonists, 5-lipoxygenase activating protein inhibitors, 5-lipoxygenase inhibitors, lipoxygenase modulators, lipoprotein lipase inhibitors, LITAF gene inhibitors, liver X receptor agonists and antagonists, liver X receptor alpha inverse agonists, liver X receptor beta inverse agonists, LPL gene stimulators, lymphocyte function antigen-3 receptor antagonists, Lyn tyrosine kinase inhibitors, Lyn tyrosine kinase stimulators, lysophosphatidic acid-1 receptor antagonists, lysyl oxidase homolog (LOXL) 2 inhibitors, LXR inverse agonists, macrophage drug conjugates (MDC), macrophage inflammatory protein (MIP) 2α inhibitors, MIP 2β inhibitors, MIP 3α ligand inhibitors, macrophage mannose receptor 1 modulators, macrophage migration inhibitory factor inhibitors, MAdCAM inhibitors, MAdCAM modulators, MALT protein 1 inhibitors, mannan-binding lectin serine protease 2 inhibitors, MAP kinase inhibitors, MAP kinase kinase 4 inhibitors, MAP kinase modulators, MAP3K2 gene inhibitors, MAPKAPK2 inhibitors, MAPKAPK5 inhibitors, matrix extracellular phosphoglycoprotein modulators, matrix metalloproteinase inhibitors, MCH receptor 1 antagonists, MCL1 gene inhibitors, M EK protein kinase inhibitors, MEK-1 protein kinase inhibitors, MEK-2 protein kinase inhibitors, MEKK-5 protein kinase inhibitors, melanin concentrating hormone (MCH-1) antagonists, melanocortin agonists, melanocortin MC1 receptor agonists, melanocortin MC3 receptor agonists, melanocortin receptor agonists, membrane copper amine oxidase inhibitors, metalloproteinase-1 inhibitors, metalloproteinase-2 inhibitors, metalloproteinase-9 inhibitors, metalloproteinase-9 stimulators, methylprednisolone, methionine aminopeptidase-2 inhibitors, methyl CpG binding protein 2 modulators,Microbiome targeted therapeutics, microRNA-132 (miR-132) antagonists, microRNA-21 (miR-21) inhibitors, midkine ligand inhibitors, mineralocorticoid receptor antagonists and modulators, mitochondrial uncouplers, mitochondrial 10kDa heat shock protein stimulators, mitochondrial pyruvate carrier 2 inhibitors, mitochondrial pyruvate carrier 2 inhibitors, mixed lineage kinase 3 inhibitors, MKL myocardin-like protein inhibitors, MNK protein kinase inhibitors, monocarboxylate transporter inhibitors, monocyte macrophage differentiation inhibitors, motile sperm domain protein 2 inhibitors, MST-1 protein kinase inhibitors, mTOR complex 1 inhibitors, mTOR complex 2 inhibitors, mTOR inhibitors, myelin basic protein stimulators, myeloperoxidase inhibitors, myosin 2 inhibitors, N-formyl peptide receptor antagonists, NACHT LRR PYD domain protein 3 (NLRP3) inhibitors, NADADP ribosyltransferase stimulators, NAD-dependent deacetylase longevity protein stimulators, NAD-dependent deacetylase longevity protein-1 stimulators, NADPH oxidase inhibitors, NADPH oxidase 1 inhibitors, NADPH oxidase 4 inhibitors, NAMPT gene inhibitors, natriuretic peptide receptor C agonists, neuregulin-4 ligands, neuropilin 2 modulators, neutral endopeptidase inhibitors, NFκB inhibitor stimulators, NFAT gene inhibitors, NFE2L2 gene inhibitors, NFE2L2 gene stimulators, nicotinic acetylcholine receptor antagonists, nicotinic acid receptor 1 agonists, nicotinamide phosphoribosyltransferase inhibitors, NK cell receptor modulators, NK1 receptor antagonists, NKG2 AB activated NK receptor antagonists, NKG2 D activated NK receptor antagonist, NLR family member X1 stimulator, NLRP3 inhibitor, NMDA receptor ε2 subunit inhibitor, NOD2 gene modulator, non-receptor tyrosine kinase TYK2 antagonist, NOX4 gene inhibitor, NUAK SNF1-like protein kinase 1 inhibitors, erythroid 2-related factor 2 stimulators, nuclear factor kappa (NFK) B inhibitors and modulators, nuclear factor kappa B p105 inhibitors, nuclear hormone receptor modulators, nuclear pore complex protein modulators, nuclear receptor modulators, nuclease stimulators, nucleoside reverse transcriptase inhibitors, nucleosome assembly protein 1-like-4 inhibitors, oncostatin M receptor modulators, oncostatin M receptor subunit beta inhibitors, opioid receptor antagonists, opioid growth factor receptor agonists, opioid receptor delta, kappa and mu antagonists, opioid receptor sigma antagonist 1, orphan nuclear receptor antagonists, osteoclast differentiation factor antagonists, osteoclast differentiation factor ligand inhibitors, oxidoreductase inhibitors, OX40 ligand inhibitors, OX-40 receptor antagonists and modulators, oxyntomodulin ligands, PGE1 agonists, P-glycoprotein inhibitors, P-selectin glycoprotein ligand-1, 14-3-3 protein η inhibitors, P2X3 purinergic receptor antagonists,P2X7 purinergic receptor agonists and modulators, P2Y6 purinergic receptor modulators, P2Y13 purinergic receptor stimulators, p38 MAP kinase alpha inhibitors, p38 MAP kinase inhibitors, p53 tumor suppressor protein stimulators, PACAP type I receptor agonists, Pan cathepsin inhibitors, parathyroid hormone ligand inhibitors, PARP modulators, PDE 1 inhibitors, PDE 3 inhibitors, PDE 4 inhibitors, PDE 4b inhibitors, PDE 5 inhibitors, PDGF-B ligand inhibitors, PDGF receptor agonists, PDGF receptor α antagonists, PDGF receptor β antagonists and modulators, pegylated long-acting glucagon-like peptide-1 / glucagon receptor (GLP-1R / GCGR) dual receptor agonists, Pellino homolog 1 inhibitors, peptidyl-prolyl cis-trans isomerase A inhibitors, peptidyl-prolyl cis-trans isomerase D inhibitors, PERK gene inhibitors, PGI2 agonists, PGD2 antagonists, phenylalanine hydroxylase stimulators, phosphatidylinositol 3-kinase subunit 3 inhibitors, phosphoinositide receptor agonists agents, phosphoinositide 3-kinase inhibitors, phosphoinositide 3-kinase alpha, delta and gamma inhibitors, phospholipase A2 inhibitors, phospholipase C inhibitors, phosphodiesterase inhibitors, phosphorylase inhibitors, plasma retinol binding protein inhibitors, plasminogen activator inhibitor 1 inhibitors, plasmin stimulators, platelet activating factor receptor antagonists, plexin domain-containing protein stimulators, PNPLA3 gene inhibitors and modulators, potassium channel inhibitors PPAR agonists, PPAR alpha / delta agonists, PPAR delta agonists, PPAR gamma agonists and modulators, PRKAA2 gene stimulators, procedures PDL1 modulators, programmed cell death protein 1 modulators, programmed cell death protein 1 stimulators, proprotein convertase PC9 inhibitors, prostaglandin (PGI2) agonists, prostaglandin D synthase stimulators, prostaglandin receptor antagonists, protease-activated receptor-2 antagonists, proteasome beta-8 subunit modulators, proteasome inhibitors, protein arginine deiminase inhibitors, protein arginine deiminase IV inhibitors, protein C activators, protein cerebellum protein modulators, protein fimH inhibitors, protein kinase Cθ inhibitors, protein kinase inhibitors and modulators, protein White kinase Cθ inhibitors, protein MB21D1 inhibitors and modulators, protein NOV homologous modulators, P-selectin glycoprotein ligand-1 inhibitors, protein tyrosine kinase inhibitors, protein tyrosine phosphatase β inhibitors, protein tyrosine phosphatase 1B inhibitors, protein tyrosine phosphatase 2C inhibitors, protein tyrosine phosphatase 1E inhibitors, P-selectin glycoprotein ligand-1 stimulators, PTGS2 gene inhibitors, PurH purine biosynthesis protein inhibitors, QSK serine threonine protein kinase inhibitors, Ras gene inhibitors, reactive oxygen species regulator inhibitors, relaxin receptor modulators,Relaxin receptor 2 modulators, renin inhibitors, resistin ligand inhibitors, resistin / CAP1 (adenylate cyclase-associated protein 1) interaction inhibitors, retinoic acid receptor agonists, retinoic acid receptor gamma antagonists and inverse agonists, retinoid receptor agonists, retinoid X receptor agonists and modulators, retinoid Z receptor gamma agonists and antagonists, Ret tyrosine kinase receptor inhibitors, Rev protein modulators, Rho-associated protein kinase inhibitors, Rho-associated protein kinase 1 inhibitors, Rho-associated protein kinase 2 inhibitors, Rhomboid family member 2 inhibitors, ribonuclease P inhibitors, RIP-1 kinase inhibitors, RIP-2 kinase inhibitors, RNA polymerase inhibitors, Sepra se inhibitors, serine threonine protein kinase TBK1 inhibitors, serine threonine protein kinase TBK1 modulators, serine threonine SNF1-like kinase 2 inhibitors, SERPINH1 gene inhibitors, serum amyloid A modulators, serum amyloid P stimulators, signal transduction factor CD24 modulators, signal transduction inhibitors, SLC22A12 inhibitors, SMAD inhibitors, SMAD-3 inhibitors, smoothened receptor antagonists, S-nitrosoglutathione reductase (GSNOR) inhibitors, sodium channel inhibitors, sodium glucose transporter-1 inhibitors, sodium glucose transporter-2 inhibitors, solute carrier family inhibitors, somatostatin receptor agonists, sphingolipid delta 4 desaturase DES1 inhibitors preparations, sphingosine kinase 1 inhibitors, sphingosine kinase 2 inhibitors, sphingosine phosphate 1 phosphatase modulators, sphingosine phosphate 1 phosphatase stimulators, sphingosine-1-phosphate receptor-1 agonists, sphingosine-1-phosphate receptor-5 agonists, sphingosine-1-phosphate receptor-1 antagonists, sphingosine-1-phosphate receptor-1 modulators, sphingosine-1-phosphate receptor-3 modulators, sphingosine-1-phosphate receptor-4 modulators, sphingosine-1-phosphate receptor-5 modulators, Src tyrosine kinase inhibitors, SREBP transcription factor inhibitors, SREBP transcription factor 1 inhibitors, SREBP transcription factor 2 inhibitors, STAT inhibitors, STAT3 gene inhibitors, STAT-1 inhibitors and modulators, S TAT-3 inhibitors and modulators, STAT-5 inhibitors, STAT-6 inhibitors, stearoyl CoA desaturase-1 inhibitors, stem cell antigen-1 inhibitors, interferon gene stimulator protein inhibitors, STK25 inhibitors, stress-induced secretory protein 1 stimulators, superoxide dismutase modulators, superoxide dismutase stimulators, cytokine signaling inhibitor-1 stimulators, cytokine signaling inhibitor-3 stimulators, SYK inhibitors, syndecan-1 inhibitors, TACE inhibitors, TAK1 binding protein modulators, talin modulators, taste receptor type 2 agonists, T-box transcription factor TBX21 modulators, T cell differentiation antigen CD6 inhibitors, T cell receptor modulators,T cell receptor antagonists, T cell surface glycoprotein CD1a inhibitors, T cell surface glycoprotein CD8 inhibitors, T cell surface glycoprotein CD28 inhibitors, T cell surface glycoprotein CD8 regulators, T cell surface glycoprotein CD28 stimulators, T cell transcription factor NFAT regulators, Tec tyrosine kinase inhibitors, telomerase stimulators, tenascin regulators, TERT gene regulators, TGF-β activated kinase-1 inhibitors, TGF-β activation regulators, TGF-β agonists, TGF-β ligand inhibitors, TGF-β1 ligand inhibitors, TGF-β3 ligand inhibitors, TGF-β1 gene inhibitors, TGF-β1 ligand regulators, TGF-β receptor antagonists, TGF-β Type II receptor antagonists, TGFB1 gene inhibitors, thromboxane reductase inhibitors, thromboxane stimulators, thromboxane A2 antagonists, thromboxane A2 receptor antagonists, thromboxane synthesis inhibitors, thymic stromal lymphopoietin ligand inhibitors, thymic stromal lymphopoietin ligand modulators, thymic stromal lymphopoietin receptor modulators, thymosin agonists, thyroid hormone receptor agonists, thyroid hormone receptor β agonists, tissue transglutaminase inhibitors, Toll-like receptor (TLR)-2 antagonists, TLR-3 antagonists, TLR-4 antagonists, TLR-7 antagonists and modulators, TLR-8 antagonists, TLR-9 antagonists and agonists, TLR modulators, TNFα ligand agonists agonists and antagonists, TNF ligand agonists and antagonists, TNF binders, TNF gene inhibitors, TNFSF11 gene inhibitors, topoisomerase II inhibitors, TPL-2 inhibitors, transaminase stimulators, transcription factor regulators, transcription factor p65 inhibitors, transcription factor RelB inhibitors, transferrin regulators, transforming growth factor beta (TGF-β), transforming growth factor beta activated kinase 1 (TAK1), transglutaminase inhibitors, transthyretin regulators, TrkA receptor antagonists, Trk tyrosine kinase receptor inhibitors, TRP cation channel A1 inhibitors, TRP cation channel C5 inhibitors, TRP cation channel C6 inhibitors, tryptophan 5-hydroxylase-1 inhibitors, Tryptophanase inhibitors, Tubulin binding agents, Tumor necrosis factor ligand inhibitors, Tumor necrosis factor ligand 13 inhibitors, Tumor necrosis factor 15 ligand inhibitors, Tumor necrosis factor 14 ligand modulators, Tumor necrosis factor 13C receptor antagonists, Tumor necrosis factor 14 ligand inhibitors, Tyk2 tyrosine kinase inhibitors, Type I IL-1 receptor antagonists, Type I TNF receptor antagonists, Type II TNF receptor antagonists, Type II TNF receptor modulators, Tyrosine kinase receptor inhibitors, Tyrosine kinase receptor modulators, Ubiquitin ligase modulators and stimulators, Ubiquitin thioesterase-30 inhibitors, Uncoupling protein modulators, Unspecified cell adhesion molecule inhibitors, Unspecified GPCR agonists, Unspecified GPCR modulators,Unspecified growth factor receptor antagonists, urate anion exchanger 1 inhibitors, vanilloid VR1 agonists, vanilloid VR1 antagonists, vasopressin V1a receptor antagonists, VDR agonists, VEGF receptor antagonists, VEGF receptor modulators, VEGF-1 receptor antagonists, VEGF-2 receptor antagonists, VEGF-3 receptor antagonists, VEGF-2 receptor modulators, VEGF-B ligand inhibitors, vimentin inhibitors, VIP 1 receptor agonists, VIP 2 receptor agonists, vitamin D3 receptor agonists, vitamin D3 receptor modulators, vitamin K-dependent protein C stimulators, WNT modulators, Wnt ligand inhibitors, Wnt 5A ligand inhibitors, xanthine oxidase inhibitors, X-linked inhibitor of apoptosis protein inhibitors, XPO1 gene modulators, YAP / TAZ modulators, YSK-4 protein kinase inhibitors, Zap70 tyrosine kinase inhibitors, zinc finger binding protein Aiolos inhibitors, and zonulin inhibitors.

199. The method or antibody or antigen-binding fragment thereof of any one of claims 142 to 198, wherein the subject is a human subject.

200. A method of downregulating an immune response in a subject, the method comprising administering to the subject an antibody or antigen-binding fragment thereof according to any one of claims 1 to 131 or an immunoconjugate according to claim 137, or administering to the subject a pharmaceutical composition according to claim 138.

201. A method of inhibiting an immune cell expressing CD200R, the method comprising contacting the immune cell with the antibody or antigen-binding fragment thereof according to any one of claims 1 to 131 or the immunoconjugate according to claim 137.

202. The method of claim 201, wherein the immune cells comprise T cells, B cells or macrophages.

203. The method of claim 201, wherein the immune cells comprise antigen-specific T cells.

204. The method of any one of claims 201 to 203, wherein: (a) the HCVR comprises a heavy chain complementary determining region 1 (CDRH1), CDRH2 and CDRH3, and wherein CDRH1, CDRH2 and CDRH3 comprise the sequences shown in SEQ ID NOs: 3, 41 and 70, respectively, each having 0 to 3 amino acid modifications, such as 0, 1, 2 or 3 modifications; and the LCVR comprises a light chain complementary determining region 1 (CDRL1), CDRL2 and CDRL3, and wherein CDRL1, CDRL2 and CDRL3 comprise the sequences shown in SEQ ID NOs: 6, 67 and 8, respectively, each having 0 to 3 amino acid modifications, such as 0, 1, 2 or 3 modifications; (b) the HCVR comprises a heavy chain complementary determining region 1 (CDRH1), CDRH2 and CDRH3, and wherein CDRH1, CDRH2 and CDRH3 comprise the sequences shown in SEQ ID NOs: 3, 41 and 5, respectively, each having 0 to 3 amino acid modifications, such as 0, 1, 2 or 3 modifications; and the LCVR comprises a light chain complementary determining region 1 (CDRL1), CDRL2 and CDRL3, and wherein CDRL1, CDRL2 and CDRL3 comprise the sequences shown in SEQ ID NOs: 6, 67 and 8, respectively, each having 0 to 3 amino acid modifications, such as 0, 1, 2 or 3 modifications; (c) the HCVR comprises an amino acid sequence that has at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence set forth in SEQ ID NO:72, and the LCVR comprises an amino acid sequence that has at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence set forth in SEQ ID NO:65; (d) the HCVR comprises the amino acid sequence as set forth in SEQ ID NO:72, having 0 to 10 amino acid modifications, such as 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid modifications, and the LCVR comprises the amino acid sequence as set forth in SEQ ID NO:65, having 0 to 10 amino acid modifications, such as 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid modifications; (e) the HCVR comprises an amino acid sequence that has at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence set forth in SEQ ID NO:71, and the LCVR comprises an amino acid sequence that has at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence set forth in SEQ ID NO:65; (f) the HCVR comprises the amino acid sequence as set forth in SEQ ID NO:71, having 0 to 10 amino acid modifications, such as 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid modifications, and the LCVR comprises the amino acid sequence as set forth in SEQ ID NO:65, having 0 to 10 amino acid modifications, such as 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid modifications; (g) the HCVR comprises an amino acid sequence that has at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence set forth in SEQ ID NO:93, and the LCVR comprises an amino acid sequence that has at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence set forth in SEQ ID NO:94; (h) the HCVR comprises the amino acid sequence as set forth in SEQ ID NO:93, having 0 to 10 amino acid modifications, such as 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid modifications, and the LCVR comprises the amino acid sequence as set forth in SEQ ID NO:94, having 0 to 10 amino acid modifications, such as 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid modifications; (i) the antibody or antigen-binding fragment thereof comprises: a heavy chain comprising an amino acid sequence having at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence shown in SEQ ID NO:82, and a light chain comprising an amino acid sequence having at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence shown in SEQ ID NO:86; (j) the antibody or antigen-binding fragment thereof comprises: a heavy chain comprising the amino acid sequence as shown in SEQ ID NO: 82, having 0 to 10 amino acid modifications, such as 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid modifications, and a light chain comprising the amino acid sequence as shown in SEQ ID NO: 86, having 0 to 10 amino acid modifications, such as 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid modifications; (k) the antibody or antigen-binding fragment thereof comprises: a heavy chain comprising an amino acid sequence having at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence shown in SEQ ID NO:83, and a light chain comprising an amino acid sequence having at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence shown in SEQ ID NO:86; (l) the antibody or antigen-binding fragment thereof comprises: a heavy chain comprising the amino acid sequence as shown in SEQ ID NO:83, having 0 to 10 amino acid modifications, such as 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid modifications, and a light chain comprising the amino acid sequence as shown in SEQ ID NO:86, having 0 to 10 amino acid modifications, such as 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid modifications; (m) the antibody or antigen-binding fragment thereof comprises: a heavy chain comprising an amino acid sequence having at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence shown in SEQ ID NO:84, and a light chain comprising an amino acid sequence having at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence shown in SEQ ID NO:86; (n) the antibody or antigen-binding fragment thereof comprises: a heavy chain comprising the amino acid sequence as shown in SEQ ID NO:84, having 0 to 10 amino acid modifications, such as 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid modifications, and a light chain comprising the amino acid sequence as shown in SEQ ID NO:86, having 0 to 10 amino acid modifications, such as 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid modifications; (o) the antibody or antigen-binding fragment thereof comprises: a heavy chain comprising an amino acid sequence having at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence shown in SEQ ID NO:85, and a light chain comprising an amino acid sequence having at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence shown in SEQ ID NO:86; (p) the antibody or antigen-binding fragment thereof comprises: a heavy chain comprising the amino acid sequence as shown in SEQ ID NO:85, having 0 to 10 amino acid modifications, such as 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid modifications, and a light chain comprising the amino acid sequence as shown in SEQ ID NO:86, having 0 to 10 amino acid modifications, such as 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid modifications; (q) the antibody or antigen-binding fragment thereof comprises: a heavy chain comprising an amino acid sequence having at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence shown in SEQ ID NO:95, and a light chain comprising an amino acid sequence having at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence shown in SEQ ID NO:98; (r) the antibody or antigen-binding fragment thereof comprises: a heavy chain comprising the amino acid sequence as shown in SEQ ID NO:95, having 0 to 10 amino acid modifications, such as 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid modifications, and a light chain comprising the amino acid sequence as shown in SEQ ID NO:98, having 0 to 10 amino acid modifications, such as 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid modifications; (s) the antibody or antigen-binding fragment thereof comprises: a heavy chain comprising an amino acid sequence having at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence as shown in SEQ ID NO:96, and a light chain comprising an amino acid sequence having at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence as shown in SEQ ID NO:98; (t) the antibody or antigen-binding fragment thereof comprises: a heavy chain comprising the amino acid sequence as shown in SEQ ID NO:96, having 0 to 10 amino acid modifications, such as 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid modifications, and a light chain comprising the amino acid sequence as shown in SEQ ID NO:98, having 0 to 10 amino acid modifications, such as 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid modifications; (u) the antibody or antigen-binding fragment thereof comprises: a heavy chain comprising an amino acid sequence having at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence shown in SEQ ID NO:97, and a light chain comprising an amino acid sequence having at least 90%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence shown in SEQ ID NO:98; or (v) the antibody or antigen-binding fragment thereof comprises: a heavy chain comprising the amino acid sequence as shown in SEQ ID NO:97, having 0 to 10 amino acid modifications, such as 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid modifications, and a light chain comprising the amino acid sequence as shown in SEQ ID NO:98, having 0 to 10 amino acid modifications, such as 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid modifications.

205. The method of any one of claims 201 to 204, wherein the subject is a human subject.

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