Engineered CD200R antibodies and uses thereof

Abstract

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

Description

[Background technology]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims the benefit under 35 U.S.C. §119(e) of U.S. Provisional Application No. 63 / 328,015, filed April 6, 2022, and U.S. Provisional Application No. 63 / 348,532, filed June 3, 2022, which are hereby incorporated by reference in their entireties for all purposes.

[0002] Sequence Listing This application contains a Sequence Listing that has been submitted electronically in XML file format, which is incorporated by reference in its entirety. The XML copy created on Mar. 31, 2023 is named 210196-209003_PCT.xml and is 112,069 bytes in size. Summary of the Invention

[0003] Disclosed herein, in some aspects, is an antibody or antigen-binding fragment thereof that specifically binds to CD200R, comprising a heavy chain comprising at least one heavy chain complementarity determining region (CDR) set forth in any of SEQ ID NOs: 3, 4, 41, 5, 11, 12, 13, 19, 20, 21, 27, 28, 29, 35, 36, 37, 69, 70, or 91, having 0-3 amino acid modifications.

[0004] Disclosed herein, in some aspects, is an antibody or antigen-binding fragment thereof that specifically binds to CD200R, comprising a heavy chain and a light chain, wherein the heavy chain comprises a heavy chain variable region comprising heavy chain complementarity determining region 1 (CDRH1), CDRH2, and CDRH3, and wherein CDRH1, CDRH2, and CDRH3 are selected from the group consisting of (a) SEQ ID NOs: 3, 41, and 70, each having 0-3 amino acid modifications, such as 0, 1, 2, or 3 modifications each; (b) SEQ ID NOs: 3, 41, and 69, each having 0-3 amino acid modifications, such as 0, 1, 2, or 3 modifications each; (c) SEQ ID NOs: 3, 4, and 5, each having 0-3 amino acid modifications, such as 0, 1, 2, or 3 modifications each; and (d) SEQ ID NOs: 3, 4, and 5, each having 0-3 amino acid modifications, such as 0, 1, 2, or 3 modifications each. (e) SEQ ID NOs: 11, 12, and 13, respectively, having 0 to 3 amino acid modifications, such as 0, 1, 2 or 3 modifications each; (f) SEQ ID NOs: 19, 20, and 21, respectively, having 0 to 3 amino acid modifications, such as 0, 1, 2 or 3 modifications each; (g) SEQ ID NOs: 27, 28, and 29, respectively, having 0 to 3 amino acid modifications, such as 0, 1, 2 or 3 modifications each; or (h) SEQ ID NOs: 35, 36, and 37, respectively, having 0 to 3 amino acid modifications, such as 0, 1, 2 or 3 modifications each.

[0005] Disclosed herein, in some embodiments, is an antibody or antigen-binding fragment thereof that specifically binds to CD200R, comprising a light chain comprising at least one light chain complementarity determining region (CDR) set forth in any of SEQ ID NOs: 6, 7, 8, 14, 15, 16, 22, 23, 24, 30, 31, 32, 38, 39, 40, 67, 68, or 87-91, having 0-3 amino acid modifications.

[0006] Disclosed herein, in some aspects, 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 light chain complementarity determining region 1 (CDRL1), CDRL2, and CDRL3, and wherein CDRL1, CDRL2, and CDRL3 are selected from the group consisting of (a) SEQ ID NOs: 6, 7, and 8, each having 0-3 amino acid modifications, such as 0, 1, 2, or 3 modifications each; (b) SEQ ID NOs: 14, 15, and 16, each having 0-3 amino acid modifications, such as 0, 1, 2, or 3 modifications each; (c) SEQ ID NOs: 22, 23, and 24, each having 0-3 amino acid modifications, such as 0, 1, 2, or 3 modifications each; (d) SEQ ID NOs: 0, 1 ... an antibody or antigen-binding fragment thereof comprising the sequence of SEQ ID NOs: 30, 31, and 32, each having 0 to 3 amino acid modifications, such as 0, 1, 2 or 3 modifications; (e) SEQ ID NOs: 38, 39, and 40, each having 0 to 3 amino acid modifications, such as 0, 1, 2 or 3 modifications, respectively; (f) SEQ ID NOs: 6, 67, and 8, each having 0 to 3 amino acid modifications, such as 0, 1, 2 or 3 modifications, respectively; or (g) SEQ ID NOs: 6, 68, and 8, each having 0 to 3 amino acid modifications, such as 0, 1, 2 or 3 modifications, respectively.

[0007] Disclosed herein, in some embodiments, is an antibody or antigen-binding fragment thereof that specifically binds to CD200R, comprising: (a) a heavy chain comprising at least one heavy chain CDR set forth in any of SEQ ID NOs: 3, 4, 41, 5, 69, or 70, and having 0-3 amino acid modifications; and (b) a light chain comprising at least one light chain CDR set forth in any of SEQ ID NOs: 3, 4, 41, 5, 69, or 70, and having 0-3 amino acid modifications; (c) a heavy chain comprising at least one heavy chain CDR set forth in any of SEQ ID NOs: 3, 4, 41, 5, 69, or 70 and at least one light chain CDR set forth in any of SEQ ID NOs: 6, 68, or 8 and having 0 to 3 amino acid modifications; (d) a light chain comprising at least one heavy chain CDR set forth in any of SEQ ID NOs: 3, 41, or 5, 69, or 70 and having 0 to 3 amino acid modifications; 70, and at least one light chain CDR of SEQ ID NO: 6, 67, or 8 having 0 to 3 amino acid modifications; (e) a heavy chain comprising at least one heavy chain CDR of SEQ ID NO: 3, 41, or 69, and at least one light chain CDR of SEQ ID NO: 6, 67, or 8 having 0 to 3 amino acid modifications; (f) a light chain comprising at least one heavy chain CDR of SEQ ID NO: 6, 67, or 8 having 0 to 3 amino acid modifications; (g) a heavy chain comprising at least one heavy chain CDR set forth in any of SEQ ID NOs: 11, 12, or 13, and at least one light chain CDR set forth in any of SEQ ID NOs: 14, 15, or 16, having 0 to 3 amino acid modifications; (g) a light chain comprising at least one heavy chain CDR set forth in any of SEQ ID NOs: 19, 20, or 21, having 0 to 3 amino acid modifications, and at least one light chain CDR set forth in any of SEQ ID NOs: 22, 23, or 24, having 0 to 3 amino acid modifications;(h) an antibody or antigen-binding fragment thereof comprising a heavy chain comprising at least one heavy chain CDR set forth in any of SEQ ID NOs: 27, 28, or 29 and having 0 to 3 amino acid modifications, and a light chain comprising at least one light chain CDR set forth in any of SEQ ID NOs: 30, 31, or 32 and having 0 to 3 amino acid modifications; or (i) a heavy chain comprising at least one heavy chain CDR set forth in any of SEQ ID NOs: 35, 36, or 37 and having 0 to 3 amino acid modifications, and a light chain comprising at least one light chain CDR set forth in any of SEQ ID NOs: 38, 39, or 40 and having 0 to 3 amino acid modifications.

[0008] Disclosed herein, in some aspects, 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 comprising heavy chain complementarity determining region 1 (CDRH1), CDRH2, and CDRH3, wherein CDRH1, CDRH2, and CDRH3 comprise the sequences set forth in SEQ ID NOs: 3, 41, and 70, respectively, each having 0-3 amino acid modifications, such as 0, 1, 2, or 3 modifications; and (2) the light chain comprises a light chain variable region comprising light chain complementarity determining region 1 (CDRL1), CDRL2, and CDRL3, wherein CDRL1, CDRL2, and CDRH3 each have 0, 1, 2, or 3 modifications. (2) the heavy chain comprises a heavy chain variable region comprising a heavy chain complementarity determining region 1 (CDRH1), CDRH2, and CDRH3, and CDRH1, CDRH2, and CDRH3 comprise the sequences set forth in SEQ ID NOs: 3, 41, and 5, respectively, with 0-3 amino acid modifications, such as 0, 1, 2, or 3 modifications, each; or (3) the heavy chain comprises a heavy chain variable region comprising a light chain complementarity determining region 1 (CDRL1), CDRL2, and CDRH3, and CDRH1, CDRH2, and CDRH3 comprise the sequences set forth in SEQ ID NOs: 3, 41, and 5, respectively, with 0-3 amino acid modifications, such as 0, 1, 2, or 3 modifications, each; (3) the heavy chain comprises a heavy chain variable region comprising a heavy chain complementarity determining region 1 (CDRH1), a CDRH2, and a CDRH3, and wherein CDRH1, CDRH2, and CDRH3 comprise the sequences set forth in SEQ ID NOs: 6, 67, and 8, respectively, with 0-3 amino acid modifications, such as 0, 1, 2, or 3 modifications each; or (4) the light chain comprises a light chain complementarity determining region 1 (CDRL1), a light chain complementarity determining region 2 (CDRH2), a light chain complementarity determining region 3 (CDRH3), a light chain complementarity determining region 4 (CDRH4), a light chain complementarity determining region 5 (CDRH5), a light chain complementarity determining region 6 (CDRH6), a light chain complementarity determining region 7 (CDRH7), a light chain complementarity determining region 8 (CDRH8), a light chain complementarity determining region 9 (CDRH9), a light chain complementarity determining region 10 (CDRH10), a light chain complementarity determining region 11 (CDRH11), a light chain complementarity determining region 12 (CDRH12), a light chain complementarity determining region 13 (CDRH13), a light chain complementarity determining region 14 (CDRH14), a light chain complementarity determining region 15 (CDRH15), a light chain complementarity determining region 16 (CDRH16), a light chain complementarity determining region 17 (CDRH17), a light chain complementarity determining region 18 (CDRH18), a light chain complementarity determining region 19 (CDRH19), a light chain complementarity determining region 20 (CDRH19), a light chain complementarity determining region 21 (CDRH19), a light chain complementarity determining region 22 (CDRH19), a light chain complementarity determining region 23 (CDRH19), a light chain complementarity determining region 24 (CDRH19), a light chain complementarity determining region 25 (CDRH19), a light chain complementarity determining region 26 (CDRH19), a light (4) the heavy chain comprises a heavy chain variable region comprising CDRH1, CDRH2, and CDRH3, wherein CDRH1, CDRH2, and CDRH3 comprise the sequences set forth in SEQ ID NOs: 6, 7, and 8, respectively, with 0 to 3 amino acid modifications, such as 0, 1, 2, or 3 modifications each; or (5) the heavy chain comprises a heavy chain variable region comprising CDRH1, CDRH2, and CDRH3, wherein CDRH1, CDRH2, and CDRH3 comprise the sequences set forth in SEQ ID NOs: 3, 41, and 5, respectively, with 0 to 3 amino acid modifications, such as 0, 1, 2, or 3 modifications each;and CDRL3, wherein CDRL1, CDRH2, and CDRH3 comprise the sequences set forth in SEQ ID NOs: 6, 7, and 8, respectively, with 0-3 amino acid modifications, such as 0, 1, 2, or 3 modifications each; or (5) the heavy chain comprises a heavy chain variable region comprising CDRH1, CDRH2, and CDRH3, wherein CDRH1, CDRH2, and CDRH3 comprise the sequences set forth in SEQ ID NOs: 11, 12, and 13, respectively, with 0-3 amino acid modifications, such as 0, 1, 2, or 3 modifications each; and the light chain comprises a and wherein CDRL1, CDRH2, and CDRH3 each comprise the sequences set forth in SEQ ID NOs: 14, 15, and 16, respectively, with 0-3 amino acid modifications, such as 0, 1, 2, or 3 modifications, or (6) the heavy chain comprises a heavy chain variable region comprising CDRH1, CDRH2, and CDRH3, and wherein CDRH1, CDRH2, and CDRH3 each comprise the sequences set forth in SEQ ID NOs: 19, 20, and 21, respectively, with 0-3 amino acid modifications, such as 0, 1, 2, or 3 modifications, and the light chain comprises CDRL1, CDRL2, and CDRL3 (6) the heavy chain comprises a heavy chain variable region comprising CDRH1, CDRH2, and CDRH3, each of which comprises the sequences set forth in SEQ ID NOs: 22, 23, and 24, and wherein CDRH1, CDRH2, and CDRH3 each of which comprises the sequences set forth in SEQ ID NOs: 27, 28, and 29 ... (8) the heavy chain comprises a heavy chain variable region comprising CDRH1, CDRH2, and CDRH3, and CDRH1, CDRH2, and CDRH3 comprise sequences set forth in SEQ ID NOs: 30, 31, and 32, respectively, with 0-3 amino acid modifications, such as 0, 1, 2, or 3 modifications each; or (9) the heavy chain comprises a heavy chain variable region comprising CDRH1, CDRH2, and CDRH3, and CDRH1, CDRH2, and CDRH3 comprise sequences set forth in SEQ ID NOs: 35, 36, and 37, respectively, with 0-3 amino acid modifications, such as 0, 1, 2, or 3 modifications each; and the light chain comprises a light chain variable region comprising CDRL1, CDRL2, and CDRL3,(9) the heavy chain comprises a heavy chain variable region comprising a heavy chain complementarity determining region 1 (CDRH1), CDRH2, and CDRH3, and wherein CDRH1, CDRH2, and CDRH3 comprise sequences set forth in SEQ ID NOs: 3, 4, and 5, respectively, having 0-3 amino acid modifications, such as 0, 1, 2, or 3 modifications, each; and the light chain comprises a light chain variable region comprising a light chain complementarity determining region 1 (CDRL1), CDRL2, and CDRL3, and wherein CDRL1, CDRL2, and CDRL3 comprise 0-3 amino acid modifications, such as 0, 1, 2, or 3 modifications, each. or (10) the heavy chain comprises a heavy chain variable region comprising heavy chain complementarity determining region 1 (CDRH1), CDRH2, and CDRH3, wherein CDRH1, CDRH2, and CDRH3 comprise the sequences set forth 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 comprising light chain complementarity determining region 1 (CDRL1), CDRL2, and CDRL3, wherein CDRL1, CDRL2, and CDRL3 comprise the sequences set forth in SEQ ID NOs: 6, 68, and 8, each having 0 to 3 amino acid modifications, such as 0, 1, 2, or 3 modifications,

[0009] Disclosed herein, in some aspects, 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 heavy chain complementarity determining region 1 (CDRH1), CDRH2, and CDRH3, wherein CDRH1, CDRH2, and CDRH3 comprise the sequences set forth in SEQ ID NOs: 3, 41, and 69, respectively, with 0-3 amino acid modifications, such as 0, 1, 2, or 3 modifications each, and the light chain comprises a light chain variable region comprising light chain complementarity determining region 1 (CDRL1), CDRL2, and CDRL3, wherein CDRL1, CDRL2, and CDRL3 comprise the sequences set forth in SEQ ID NOs: 6, 90, and 8, respectively, with 0-3 amino acid modifications, such as 0, 1, 2, or 3 modifications each. In some embodiments, X at position 1 of SEQ ID NO: 69 is M. 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.

[0010] 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), and (a) the HCVR comprises heavy chain complementarity determining region 1 (CDRH1), CDRH2, and CDRH3, wherein CDRH1, CDRH2, and CDRH3 each have 0-3 amino acid modifications, such as 0, 1, 2, or 3 modifications, and comprises the sequences set forth in SEQ ID NOs: 3, 41, and 70, respectively; and (b) the LCVR comprises light chain complementarity determining region 1 (CDRL1), CDRL2, and CDRL3, wherein CDRL1, CDRL2, and CDRL3 each have 0-3 amino acid modifications, such as 0, 1, 2, or 3 modifications, 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 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 set forth in SEQ ID NO: 72 with 0-10 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 set forth in SEQ ID NO: 65 with 0-10 amino acid modifications, such as 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid modifications.

[0011] 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), and (a) the HCVR comprises heavy chain complementarity determining region 1 (CDRH1), CDRH2, and CDRH3, wherein CDRH1, CDRH2, and CDRH3 each have 0-3 amino acid modifications, such as 0, 1, 2, or 3 modifications, and comprises the sequences set forth in SEQ ID NOs: 3, 41, and 5, and (b) the LCVR comprises light chain complementarity determining region 1 (CDRL1), CDRL2, and CDRL3, wherein CDRL1, CDRL2, and CDRL3 each have 0-3 amino acid modifications, such as 0, 1, 2, or 3 modifications, and comprises the sequences set forth in SEQ ID NOs: 6, 67, and 8. 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 an amino acid sequence set forth in SEQ ID NO: 71 with 0-10 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 set forth in SEQ ID NO: 65 with 0-10 amino acid modifications, such as 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid modifications.

[0012] Disclosed herein, in some aspects, 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 complementarity determining region 1 (CDRH1) comprising the sequence set forth in SEQ ID NO: 92, (ii) a CDRH2 comprising the sequence set forth in SEQ ID NO: 41, and (iii) a CDRH3 comprising the sequence set forth in SEQ ID NO: 69, and (b) the light chain comprises a light chain variable region comprising (i) a light chain complementarity determining region 1 (CDRL1) comprising the sequence set forth in SEQ ID NO: 6, (ii) a CDRL2 comprising a sequence selected from SEQ ID NOs: 87-90, and (iii) a CDRL3 comprising the sequence 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, the X at position 3 of SEQ ID NO:92 is F. In some embodiments, the X at position 1 of SEQ ID NO:87, 88, or 89 is G. In some embodiments, the X at position 1 of SEQ ID NO:87, 88, or 89 is L. In some embodiments, the X at position 2 of SEQ ID NO:87 or 90 is A. In some embodiments, the X at position 2 of SEQ ID NO:87 or 90 is G. In some embodiments, the X at position 3 of SEQ ID NO:87 or 88 is S. In some embodiments, the X at position 3 of SEQ ID NO:87 or 88 is V. In some embodiments, the X at position 7 of SEQ ID NO:87, 88, 89, or 90 is D. In some embodiments, the X at position 7 of SEQ ID NO:87, 88, 89, or 90 is S. In some embodiments, the 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 set forth in SEQ ID NO: 72 with 0-10 amino acid modifications, and the LCVR comprises an amino acid sequence set forth in SEQ ID NO: 65 with 0-10 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 an amino acid sequence set forth in SEQ ID NO: 71 with 0-10 amino acid modifications, and the LCVR comprises an amino acid sequence set forth in SEQ ID NO: 65 with 0-10 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 an amino acid sequence set forth in SEQ ID NO: 45 with 0-10 amino acid modifications and the LCVR comprises an amino acid sequence set forth in SEQ ID NO: 65 with 0-10 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 with 0-10 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 with 0-10 amino acid modifications, such as 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 modifications.In some embodiments, the X at position 1 of SEQ ID NO:93 is D. In some embodiments, the X at position 1 of SEQ ID NO:93 is E. In some embodiments, the X at position 33 of SEQ ID NO:93 is W. In some embodiments, the X at position 33 of SEQ ID NO:93 is F. In some embodiments, the X at position 99 of SEQ ID NO:93 is M. In some embodiments, the X at position 99 of SEQ ID NO:93 is G. In some embodiments, the X at position 50 of SEQ ID NO:94 is G. In some embodiments, the X at position 50 of SEQ ID NO:94 is L. In some embodiments, the X at position 51 of SEQ ID NO:94 is A. In some embodiments, the X at position 51 of SEQ ID NO:94 is G. In some embodiments, the X at position 52 of SEQ ID NO:94 is S. In some embodiments, the X at position 52 of SEQ ID NO:94 is V. In some embodiments, the X at position 56 of SEQ ID NO:94 is D. In some embodiments, the X at position 56 of SEQ ID NO:94 is S. In some embodiments, the X at position 56 of SEQ ID NO:94 is T. In some embodiments, the X at position 96 of SEQ ID NO:94 is W. In some embodiments, the 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 set forth 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 set forth in SEQ ID NO:62 with 0-10 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 set forth 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 set forth in SEQ ID NO:64 with 0-10 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 set forth in SEQ ID NO:61.In some embodiments, the HCVR is linked to a heavy chain constant region comprising an amino acid sequence set forth in SEQ ID NO: 61 with 0-10 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 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 set forth in SEQ ID NO: 63 with 0-10 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 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 set forth in SEQ ID NO: 75 with 0-10 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 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 set forth in SEQ ID NO: 76 with 0-10 amino acid modifications. In some embodiments, the HCVR is linked to a heavy chain constant region, which 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 an 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 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 set forth in SEQ ID NO: 77 with 0-10 amino acid modifications. In some embodiments, the X at position 121 of SEQ ID NO: 77 is D. In some embodiments, the X at position 121 of SEQ ID NO: 77 is P. In some embodiments, the X at position 329 of SEQ ID NO: 77 is G. In some embodiments, the X at position 329 of SEQ ID NO: 77 is absent. In some embodiments, the X at position 330 of SEQ ID NO: 77 is K. In some embodiments, the 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 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 set forth in SEQ ID NO: 78 with 0-10 amino acid modifications. In some embodiments, the X at position 108 of SEQ ID NO: 78 is S. In some embodiments, the X at position 108 of SEQ ID NO:78 is P. In some embodiments, the X at position 326 of SEQ ID NO:78 is G. In some embodiments, the X at position 326 of SEQ ID NO:78 is absent. In some embodiments, the X at position 327 of SEQ ID NO:78 is K. In some embodiments, the X at position 327 of SEQ ID NO:78 is absent.

[0013] Disclosed herein, in some aspects, 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 heavy chain complementarity determining region 1 (CDRH1), CDRH2, and CDRH3, wherein CDRH1, CDRH2, and CDRH3 comprise the sequences set forth in SEQ ID NOs: 3, 41, and 69, respectively, each having 0-3 amino acid modifications, and the light chain comprises a light chain variable region comprising light chain complementarity determining region 1 (CDRL1), CDRL2, and CDRL3, wherein CDRL1, CDRL2, and CDRL3 comprise the sequences set forth in SEQ ID NOs: 6, 90, and 8, respectively, each having 0-3 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 an amino acid sequence set forth in SEQ ID NO: 72 with 0-10 amino acid modifications and the LCVR comprises an amino acid sequence set forth in SEQ ID NO: 65 with 0-10 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 an amino acid sequence set forth in SEQ ID NO: 71 with 0-10 amino acid modifications and the LCVR comprises an amino acid sequence set forth in SEQ ID NO: 65 with 0-10 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 an amino acid sequence set forth in SEQ ID NO: 45 with 0-10 amino acid modifications and the LCVR comprises an amino acid sequence set forth in SEQ ID NO: 65 with 0-10 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 with 0-10 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 with 0-10 amino acid modifications, such as 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 modifications. In some embodiments, the X at position 1 of SEQ ID NO: 93 is D. In some embodiments, the X at position 1 of SEQ ID NO: 93 is E. In some embodiments, the X at position 33 of SEQ ID NO:93 is W. In some embodiments, the X at position 33 of SEQ ID NO:93 is F. In some embodiments, the X at position 99 of SEQ ID NO:93 is M. In some embodiments, the X at position 99 of SEQ ID NO:93 is G. In some embodiments, the X at position 50 of SEQ ID NO:94 is G. In some embodiments, the X at position 50 of SEQ ID NO:94 is L. In some embodiments, the X at position 51 of SEQ ID NO:94 is A. In some embodiments, the X at position 51 of SEQ ID NO:94 is G. In some embodiments, the X at position 52 of SEQ ID NO:94 is S. In some embodiments, the X at position 52 of SEQ ID NO:94 is V.In some embodiments, the X at position 56 of SEQ ID NO:94 is D. In some embodiments, the X at position 56 of SEQ ID NO:94 is S. In some embodiments, the X at position 56 of SEQ ID NO:94 is T. In some embodiments, the X at position 96 of SEQ ID NO:94 is W. In some embodiments, the 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 set forth 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 set forth in SEQ ID NO:62 with 0-10 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 set forth 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 set forth in SEQ ID NO: 64 with 0-10 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 set forth in SEQ ID NO: 61. In some embodiments, the HCVR is linked to a heavy chain constant region comprising an amino acid sequence set forth in SEQ ID NO: 61 with 0-10 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 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 set forth in SEQ ID NO: 63 with 0-10 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 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 set forth in SEQ ID NO: 75 with 0-10 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 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 set forth in SEQ ID NO: 76 with 0-10 amino acid modifications. In some embodiments, the HCVR is linked to a heavy chain constant region, which 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 an 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 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 set forth in SEQ ID NO: 77 with 0-10 amino acid modifications. In some embodiments, the X at position 121 of SEQ ID NO: 77 is D. In some embodiments, the X at position 121 of SEQ ID NO: 77 is P. In some embodiments, the X at position 329 of SEQ ID NO: 77 is G. In some embodiments, the X at position 329 of SEQ ID NO: 77 is absent. In some embodiments, the X at position 330 of SEQ ID NO: 77 is K. In some embodiments, the 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 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 set forth in SEQ ID NO: 78 with 0-10 amino acid modifications. In some embodiments, the X at position 108 of SEQ ID NO: 78 is S. In some embodiments, the X at position 108 of SEQ ID NO: 78 is P. In some embodiments, the X at position 326 of SEQ ID NO: 78 is G. In some embodiments, the X at position 326 of SEQ ID NO: 78 is absent. In some embodiments, the X at position 327 of SEQ ID NO: 78 is K. In some embodiments, the X at position 327 of SEQ ID NO: 78 is absent.

[0014] 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 set forth in SEQ ID NO: 1, 9, 17, 25, 33, 42, 43, 44, 45, 46, 47, 71, 72, or 93.

[0015] In some cases, the antibody or antigen-binding fragment thereof comprises a heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 1, 9, 17, 25, 33, 42, 43, 44, 45, 46, 47, 71, 72, or 93, with 0-3 amino acid modifications.

[0016] 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 set forth in SEQ ID NO: 2, 10, 18, 26, 34, 48, 49, 50, 51, 52, 65, 66, or 94.

[0017] In some cases, the antibody or antigen-binding fragment thereof comprises a light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 2, 10, 18, 26, 34, 48, 49, 50, 51, 52, 65, 66, or 94, with 0-3 amino acid modifications.

[0018] 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 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 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 set forth in SEQ ID NO: 65; or (b) 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 set forth in SEQ ID NO: 71. or (c) a 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 set forth in SEQ ID NO: 1 and a 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 set forth in SEQ ID NO: 65; or (d) a 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 set forth in SEQ ID NO: 1 and a 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 set forth in SEQ ID NO: 2. (d) 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 set forth in SEQ ID NO:9 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 set forth in SEQ ID NO:10; or (e) 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 set forth in SEQ ID NO:11. (f) a 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 set forth in SEQ ID NO: 17, 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 set forth in SEQ ID NO: 18; or (f) a 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 set forth in SEQ ID NO: 25,(g) 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 set forth in SEQ ID NO: 33 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 set forth in SEQ ID NO: 34; or (h) 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 set forth in any one of SEQ ID NOs: 1, 42, 43, 44, 45, 46, 47, 71, 72, or 93. 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 set forth in any one of SEQ ID NOs: 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 set forth in SEQ ID NOs: 48, 49, 50, 51, 52, 65, 66, or 94. ,

[0019] 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 set forth in SEQ ID NO: 72 with 0-10 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 set forth in SEQ ID NO: 65 with 0-10 amino acid modifications, such as 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid modifications; or (b) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 65 with 0-10 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 set forth in SEQ ID NO: 65 and has 0 to 10 amino acid modifications, such as 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid modifications; or (c) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 1 and has 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 set forth in SEQ ID NO: 65 and has 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 set forth in SEQ ID NO: 9 and has 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 set forth in SEQ ID NO: 10 and has 0 to 10 amino acid modifications, such as 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid modifications; or (e) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 10 and has 0 to 10 amino acid modifications, such as 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid modifications. (f) a heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 25 and has 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 set forth in SEQ ID NO: 18 and has 0 to 10 amino acid modifications, such as 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid modifications; oror 10 amino acid modifications; (g) the heavy chain variable region comprises the amino acid sequence of 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 of 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; or (h) the heavy chain variable region comprises the amino acid sequence of any one of SEQ ID NOs: 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 set forth in SEQ ID NO: 2, 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; or (i) the heavy chain variable region comprises the amino acid sequence set forth in any one of SEQ ID 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 the amino acid sequence set forth 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.

[0020] Disclosed herein, in some aspects, are antibodies or antigen-binding fragments thereof that specifically bind to CD200R, wherein the antibodies or antigen-binding fragments thereof comprise a heavy chain comprising a heavy chain variable region, 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 set forth in SEQ ID NO: 1, 9, 17, 25, 33, 42, 43, 44, 45, 46, 47, 71, 72, or 93.

[0021] Disclosed herein, in some aspects, are antibodies or antigen-binding fragments thereof that specifically bind to CD200R, wherein the antibodies or antigen-binding fragments thereof comprise a heavy chain variable region, wherein the heavy chain variable region comprises the amino acid sequence set forth 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.

[0022] Disclosed herein, in some aspects, are antibodies or antigen-binding fragments thereof that specifically bind to CD200R, wherein the antibodies or antigen-binding fragments thereof comprise a light chain comprising a light chain variable region, 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 set forth in SEQ ID NO: 2, 10, 18, 26, 34, 48, 49, 50, 51, 52, 65, 66, or 94.

[0023] Disclosed herein, in some aspects, are antibodies or antigen-binding fragments thereof that specifically bind to CD200R, wherein the antibodies or antigen-binding fragments thereof comprise a light chain comprising a light chain variable region, wherein the light chain variable region comprises the amino acid sequence set forth 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.

[0024] Disclosed herein, in some aspects, is an antibody or antigen-binding fragment thereof that specifically binds to CD200R, 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, and wherein (a) 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 set forth in SEQ ID NO: 72 and the light chain variable region 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 100% sequence identity to the amino acid sequence set forth in SEQ ID NO: 71; (b) 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 set forth in SEQ ID NO: 71 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 set forth in SEQ ID NO: 65; or (c) the heavy chain variable region comprises an amino acid sequence having at least 90%, 95%, or (d) a 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 set forth in SEQ ID NO:9 and a 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 set forth in SEQ ID NO:10; (e) 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 set forth in SEQ ID NO: 17 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 set forth in SEQ ID NO: 18; or (f) the heavy chain variable region comprises(g) a 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 set forth in SEQ ID NO:25, 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 set forth in SEQ ID NO:26; or (g) a 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 set forth in SEQ ID NO:33. (h) a 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 set forth in SEQ ID NO: 34; or (i) a heavy chain variable region comprises an amino acid sequence having at least 90% 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. , 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence set forth 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 set forth in SEQ ID NO: 42, 43, 44, 45, 46, 47, 71, 72 or 9 3, 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 set forth in SEQ ID NO: 48, 49, 50, 51, 52, 65, 66, or 94, or an antibody or antigen-binding fragment thereof.

[0025] Disclosed herein, in some aspects, is an antibody or antigen-binding fragment thereof that specifically binds to CD200R, 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 set forth in SEQ ID NO: 72 having 0-10 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 set forth in SEQ ID NO: 65 having 0-10 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 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 light chain variable region comprises the amino acid sequence 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; or (c) the heavy chain variable region comprises the amino acid sequence 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. (d) a heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 9 and has 0-10 amino acid modifications, such as 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid modifications, and a light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 10 and has 0-10 amino acid modifications, such as 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid modifications. or (e) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 17 and has 0-10 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 set forth in SEQ ID NO: 18 and has 0-10 amino acid modifications, such as 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid modifications; or (f) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 25 and has 0-10 amino acid modifications, such as 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid modifications;(g) a heavy chain variable region comprises the amino acid sequence of 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 a light chain variable region comprises the amino acid sequence of 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; or (h) an amino acid sequence of any one of SEQ ID NOs: 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. or (i) an antibody or antigen-binding fragment thereof, comprising: (i) a heavy chain variable region comprising an amino acid sequence set forth in any one of SEQ ID NOs: 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 a light chain variable region comprising an amino acid sequence set forth 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.

[0026] 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 heavy chain complementarity determining region 1 (CDRH1), CDRH2, and CDRH3, and wherein CDRH1, CDRH2, and CDRH3 each have 0-3 amino acid modifications, such as 0, 1, 2, or 3 modifications, and comprises the sequences set forth in SEQ ID NOs: 3, 41, and 70, respectively; and (b) the LCVR comprises light chain complementarity determining region 1 (CDRL1), CDRL2, and CDRL3, and wherein CDRL1, CDRL2, and CDRL3 each have 0-3 amino acid modifications, such as 0, 1, 2, or 3 modifications, respectively. In some embodiments, the HCVR comprises heavy chain complementarity determining region 1 (CDRH1), CDRH2, and CDRH3, wherein CDRH1, CDRH2, and CDRH3 comprise the sequences set forth in SEQ ID NOs: 3, 41, and 70, respectively, each with 0-2 amino acid modifications. In some embodiments, the HCVR comprises heavy chain complementarity determining region 1 (CDRH1), CDRH2, and CDRH3, wherein CDRH1, CDRH2, and CDRH3 comprise the sequences set forth in SEQ ID NOs: 3, 41, and 70, respectively, each with 0-1 amino acid modifications. In some embodiments, the HCVR comprises heavy chain complementarity determining region 1 (CDRH1), CDRH2, and CDRH3, wherein CDRH1, CDRH2, and CDRH3 comprise the sequences set forth in SEQ ID NOs: 3, 41, and 70, respectively. In some embodiments, the LCVR comprises light chain complementarity determining region 1 (CDRL1), CDRL2, and CDRL3, where CDRL1, CDRL2, and CDRL3 comprise the sequences set forth in SEQ ID NOs: 6, 67, and 8, respectively, with 0-2 amino acid modifications each. In some embodiments, the LCVR comprises light chain complementarity determining region 1 (CDRL1), CDRL2, and CDRL3, where CDRL1, CDRL2, and CDRL3 comprise the sequences set forth in SEQ ID NOs: 6, 67, and 8, respectively, with 0-1 amino acid modifications each.In some embodiments, the LCVR comprises light chain complementarity determining region 1 (CDRL1), CDRL2, and CDRL3, where CDRL1, CDRL2, and CDRL3 comprise the sequences set forth in SEQ ID NOs: 6, 67, and 8, respectively. In some embodiments, the antibody or antigen-binding fragment thereof comprises an HCVR comprising heavy chain complementarity determining region 1 (CDRH1), CDRH2, and CDRH3, where CDRH1, CDRH2, and CDRH3 comprise the sequences set forth in SEQ ID NOs: 3, 41, and 70, respectively, and an LCVR comprising light chain complementarity determining region 1 (CDRL1), CDRL2, and CDRL3, where 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 set forth in SEQ ID NO: 72 with 0-10 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 set forth in SEQ ID NO: 72 with 0-9 amino acid modifications. In some embodiments, the HCVR comprises an amino acid sequence set forth in SEQ ID NO: 72 with 0-8 amino acid modifications. In some embodiments, the HCVR comprises an amino acid sequence set forth in SEQ ID NO: 72 with 0-7 amino acid modifications. In some embodiments, the HCVR comprises an amino acid sequence set forth in SEQ ID NO: 72 with 0-6 amino acid modifications. In some embodiments, the HCVR comprises an amino acid sequence set forth in SEQ ID NO: 72 with 0-5 amino acid modifications. In some embodiments, the HCVR comprises an amino acid sequence set forth in SEQ ID NO: 72 with 0-4 amino acid modifications. In some embodiments, the HCVR comprises an amino acid sequence set forth in SEQ ID NO: 72 with 0-3 amino acid modifications. In some embodiments, the HCVR comprises an amino acid sequence set forth in SEQ ID NO: 72 with 0-2 amino acid modifications. In some embodiments, the HCVR comprises an amino acid sequence set forth in SEQ ID NO: 72 with 0-1 amino acid modifications. In some embodiments, the HCVR comprises an amino acid sequence set forth in SEQ ID NO: 72. In some embodiments, the LCVR comprises an amino acid sequence set forth in SEQ ID NO: 65 with 0-10 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 an amino acid sequence set forth in SEQ ID NO: 65 with 0-9 amino acid modifications.In some embodiments, the LCVR comprises an amino acid sequence set forth in SEQ ID NO: 65 with 0 to 8 amino acid modifications. In some embodiments, the LCVR comprises an amino acid sequence set forth in SEQ ID NO: 65 with 0 to 7 amino acid modifications. In some embodiments, the LCVR comprises an amino acid sequence set forth in SEQ ID NO: 65 with 0 to 6 amino acid modifications. In some embodiments, the LCVR comprises an amino acid sequence set forth in SEQ ID NO: 65 with 0 to 5 amino acid modifications. In some embodiments, the LCVR comprises an amino acid sequence set forth in SEQ ID NO: 65 with 0 to 4 amino acid modifications. In some embodiments, the LCVR comprises an amino acid sequence set forth in SEQ ID NO: 65 with 0 to 3 amino acid modifications. In some embodiments, the LCVR comprises an amino acid sequence set forth in SEQ ID NO: 65 with 0 to 2 amino acid modifications. In some embodiments, the LCVR comprises an amino acid sequence set forth in SEQ ID NO: 65 with 0 to 1 amino acid modification. In some embodiments, the LCVR comprises an amino acid sequence set forth in SEQ ID NO: 65.

[0027] 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 heavy chain complementarity determining region 1 (CDRH1), CDRH2, and CDRH3, wherein CDRH1, CDRH2, and CDRH3 each have 0-3 amino acid modifications, such as 0, 1, 2, or 3 modifications, and comprises the sequences set forth in SEQ ID NOs: 3, 41, and 5, and (b) the LCVR comprises light chain complementarity determining region 1 (CDRL1), CDRL2, and CDRL3, wherein CDRL1, CDRL2, and CDRL3 each have 0-3 amino acid modifications, such as 0, 1, 2, or 3 modifications, and comprises the sequences set forth in SEQ ID NOs: 6, 67, and 8, In some embodiments, the HCVR comprises heavy chain complementarity determining region 1 (CDRH1), CDRH2, and CDRH3, wherein CDRH1, CDRH2, and CDRH3 comprise the sequences set forth in SEQ ID NOs: 3, 41, and 5, respectively, each with 0-2 amino acid modifications. In some embodiments, the HCVR comprises heavy chain complementarity determining region 1 (CDRH1), CDRH2, and CDRH3, wherein CDRH1, CDRH2, and CDRH3 comprise the sequences set forth in SEQ ID NOs: 3, 41, and 5, respectively, each with 0-1 amino acid modifications. In some embodiments, the HCVR comprises heavy chain complementarity determining region 1 (CDRH1), CDRH2, and CDRH3, wherein CDRH1, CDRH2, and CDRH3 comprise the sequences set forth in SEQ ID NOs: 3, 41, and 5, respectively. In some embodiments, the LCVR comprises light chain complementarity determining region 1 (CDRL1), CDRL2, and CDRL3, where CDRL1, CDRL2, and CDRL3 comprise the sequences set forth in SEQ ID NOs: 6, 67, and 8, respectively, with 0-2 amino acid modifications each. In some embodiments, the LCVR comprises light chain complementarity determining region 1 (CDRL1), CDRL2, and CDRL3, where CDRL1, CDRL2, and CDRL3 comprise the sequences set forth in SEQ ID NOs: 6, 67, and 8, respectively, with 0-1 amino acid modifications each.In some embodiments, the LCVR comprises light chain complementarity determining region 1 (CDRL1), CDRL2, and CDRL3, where CDRL1, CDRL2, and CDRL3 comprise the sequences set forth in SEQ ID NOs: 6, 67, and 8, respectively. In some embodiments, the antibody or antigen-binding fragment thereof comprises an HCVR comprising heavy chain complementarity determining region 1 (CDRH1), CDRH2, and CDRH3, where CDRH1, CDRH2, and CDRH3 comprise the sequences set forth in SEQ ID NOs: 3, 41, and 5, respectively, and an LCVR comprising light chain complementarity determining region 1 (CDRL1), CDRL2, and CDRL3, where 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 set forth in SEQ ID NO: 71 with 0-10 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 set forth in SEQ ID NO: 71 with 0-9 amino acid modifications. In some embodiments, the HCVR comprises an amino acid sequence set forth in SEQ ID NO: 71 with 0-8 amino acid modifications. In some embodiments, the HCVR comprises an amino acid sequence set forth in SEQ ID NO: 71 with 0-7 amino acid modifications. In some embodiments, the HCVR comprises an amino acid sequence set forth in SEQ ID NO: 71 with 0-6 amino acid modifications. In some embodiments, the HCVR comprises an amino acid sequence set forth in SEQ ID NO: 71 with 0-5 amino acid modifications. In some embodiments, the HCVR comprises an amino acid sequence set forth in SEQ ID NO: 71 with 0-4 amino acid modifications. In some embodiments, the HCVR comprises an amino acid sequence set forth in SEQ ID NO: 71 with 0-3 amino acid modifications. In some embodiments, the HCVR comprises an amino acid sequence set forth in SEQ ID NO: 71 with 0-2 amino acid modifications. In some embodiments, the HCVR comprises an amino acid sequence set forth in SEQ ID NO: 71 with 0-1 amino acid modifications. In some embodiments, the HCVR comprises an amino acid sequence set forth in SEQ ID NO: 71. In some embodiments, the LCVR comprises an amino acid sequence set forth in SEQ ID NO: 65 with 0-10 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 an amino acid sequence set forth in SEQ ID NO: 65 with 0-9 amino acid modifications.In some embodiments, the LCVR comprises an amino acid sequence set forth in SEQ ID NO: 65 with 0 to 8 amino acid modifications. In some embodiments, the LCVR comprises an amino acid sequence set forth in SEQ ID NO: 65 with 0 to 7 amino acid modifications. In some embodiments, the LCVR comprises an amino acid sequence set forth in SEQ ID NO: 65 with 0 to 6 amino acid modifications. In some embodiments, the LCVR comprises an amino acid sequence set forth in SEQ ID NO: 65 with 0 to 5 amino acid modifications. In some embodiments, the LCVR comprises an amino acid sequence set forth in SEQ ID NO: 65 with 0 to 4 amino acid modifications. In some embodiments, the LCVR comprises an amino acid sequence set forth in SEQ ID NO: 65 with 0 to 3 amino acid modifications. In some embodiments, the LCVR comprises an amino acid sequence set forth in SEQ ID NO: 65 with 0 to 2 amino acid modifications. In some embodiments, the LCVR comprises an amino acid sequence set forth in SEQ ID NO: 65 with 0 to 1 amino acid modification. In some embodiments, the LCVR comprises an amino acid sequence set forth in SEQ ID NO: 65.

[0028] 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 one to three heavy chain CDRs set forth in any 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 one to three light chain CDRs set forth in any of SEQ ID NOs: 6, 67, or 8, with 0 to 3 amino acid modifications.

[0029] 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 one to three heavy chain CDRs set forth in any 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 one to three light chain CDRs set forth in any of SEQ ID NOs: 6, 7, or 8, with 0 to 3 amino acid modifications.

[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 one to three heavy chain CDRs set forth in any of SEQ ID NOs: 3, 4, 41, 5, 69, or 70, with 0-3 amino acid modifications; and (b) a light chain comprising a light chain variable region (LCVR), wherein the LCVR comprises one to three light chain CDRs set forth in any of SEQ ID NOs: 6, 68, or 8, with 0-3 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 heavy chain complementarity determining region 1 (CDRH1), CDRH2, and CDRH3, wherein CDRH1, CDRH2, and CDRH3 each comprise a sequence set forth in SEQ ID NO: 3, 4, 5, with 0-3 amino acid modifications; and (b) a light chain comprising a light chain variable region (LCVR), wherein the LCVR comprises light chain complementarity determining region 1 (CDRL1), CDRL2, and CDRL3, wherein CDRL1, CDRL2, and CDRL3 each comprise a sequence set forth in SEQ ID NO: 6, 7, 8, with 0-3 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 set forth 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 an amino acid sequence set forth in SEQ ID NO:1 with 0-10 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 set forth in SEQ ID NO:1 with 0-9 amino acid modifications. In some embodiments, the HCVR comprises an amino acid sequence set forth in SEQ ID NO:1 with 0-8 amino acid modifications. In some embodiments, the HCVR comprises an amino acid sequence set forth in SEQ ID NO:1 with 0-7 amino acid modifications. In some embodiments, the HCVR comprises an amino acid sequence set forth in SEQ ID NO:1 with 0-6 amino acid modifications. In some embodiments, the HCVR comprises an amino acid sequence set forth in SEQ ID NO:1 with 0-5 amino acid modifications. In some embodiments, the HCVR comprises an amino acid sequence set forth in SEQ ID NO: 1 with 0-4 amino acid modifications. In some embodiments, the HCVR comprises an amino acid sequence set forth in SEQ ID NO: 1 with 0-3 amino acid modifications. In some embodiments, the HCVR comprises an amino acid sequence set forth in SEQ ID NO: 1 with 0-2 amino acid modifications. In some embodiments, the HCVR comprises an amino acid sequence set forth in SEQ ID NO: 1 with 0-1 amino acid modifications. In some embodiments, the HCVR comprises an amino acid sequence set forth in SEQ ID NO: 1. In some embodiments, the LCVR comprises an amino acid sequence set forth in SEQ ID NO: 2 with 0-10 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 an amino acid sequence set forth in SEQ ID NO: 2 with 0-9 amino acid modifications. In some embodiments, the LCVR comprises an amino acid sequence set forth in SEQ ID NO: 2 with 0-8 amino acid modifications.In some embodiments, the LCVR comprises the amino acid sequence set forth in SEQ ID NO: 2 with 0 to 7 amino acid modifications. In some embodiments, the LCVR comprises the amino acid sequence set forth in SEQ ID NO: 2 with 0 to 6 amino acid modifications. In some embodiments, the LCVR comprises the amino acid sequence set forth in SEQ ID NO: 2 with 0 to 5 amino acid modifications. In some embodiments, the LCVR comprises the amino acid sequence set forth in SEQ ID NO: 2 with 0 to 4 amino acid modifications. In some embodiments, the LCVR comprises the amino acid sequence set forth in SEQ ID NO: 2 with 0 to 3 amino acid modifications. In some embodiments, the LCVR comprises the amino acid sequence set forth in SEQ ID NO: 2 with 0 to 2 amino acid modifications. In some embodiments, the LCVR comprises the amino acid sequence set forth in SEQ ID NO: 2 with 0 to 1 amino acid modifications. In some embodiments, the LCVR comprises the amino acid sequence set forth in SEQ ID NO: 2.

[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 heavy chain complementarity determining region 1 (CDRH1), CDRH2, and CDRH3, wherein CDRH1, CDRH2, and CDRH3 each comprise a sequence set forth in SEQ ID NO: 11, 12, or 13, with 0-3 amino acid modifications; and (b) a light chain comprising a light chain variable region (LCVR), wherein the LCVR comprises light chain complementarity determining region 1 (CDRL1), CDRL2, and CDRL3, wherein CDRL1, CDRL2, and CDRL3 each comprise a sequence set forth in SEQ ID NO: 14, 15, or 16, with 0-3 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 set forth 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 set forth in SEQ ID NO: 9 with 0-10 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 set forth in SEQ ID NO: 9 with 0-9 amino acid modifications. In some embodiments, the HCVR comprises an amino acid sequence set forth in SEQ ID NO: 9 with 0-8 amino acid modifications. In some embodiments, the HCVR comprises an amino acid sequence set forth in SEQ ID NO: 9 with 0-7 amino acid modifications. In some embodiments, the HCVR comprises an amino acid sequence set forth in SEQ ID NO: 9 with 0-6 amino acid modifications. In some embodiments, the HCVR comprises an amino acid sequence set forth in SEQ ID NO: 9 with 0-5 amino acid modifications. In some embodiments, the HCVR comprises an amino acid sequence set forth in SEQ ID NO: 9 with 0-4 amino acid modifications. In some embodiments, the HCVR comprises an amino acid sequence set forth in SEQ ID NO: 9 with 0-3 amino acid modifications. In some embodiments, the HCVR comprises an amino acid sequence set forth in SEQ ID NO: 9 with 0-2 amino acid modifications. In some embodiments, the HCVR comprises an amino acid sequence set forth in SEQ ID NO: 9 with 0-1 amino acid modifications. In some embodiments, the HCVR comprises an amino acid sequence set forth in SEQ ID NO: 9. In some embodiments, the LCVR comprises an amino acid sequence set forth in SEQ ID NO: 10 with 0-10 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 an amino acid sequence set forth in SEQ ID NO: 10 with 0-9 amino acid modifications. In some embodiments, the LCVR comprises an amino acid sequence set forth in SEQ ID NO: 10 with 0-8 amino acid modifications.In some embodiments, the LCVR comprises the amino acid sequence set forth in SEQ ID NO: 10 with 0 to 7 amino acid modifications. In some embodiments, the LCVR comprises the amino acid sequence set forth in SEQ ID NO: 10 with 0 to 6 amino acid modifications. In some embodiments, the LCVR comprises the amino acid sequence set forth in SEQ ID NO: 10 with 0 to 5 amino acid modifications. In some embodiments, the LCVR comprises the amino acid sequence set forth in SEQ ID NO: 10 with 0 to 4 amino acid modifications. In some embodiments, the LCVR comprises the amino acid sequence set forth in SEQ ID NO: 10 with 0 to 3 amino acid modifications. In some embodiments, the LCVR comprises the amino acid sequence set forth in SEQ ID NO: 10 with 0 to 2 amino acid modifications. In some embodiments, the LCVR comprises the amino acid sequence set forth in SEQ ID NO: 10 with 0 to 1 amino acid modifications. In some embodiments, the LCVR comprises the amino acid sequence set forth in SEQ ID NO: 10.

[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 heavy chain complementarity determining region 1 (CDRH1), CDRH2, and CDRH3, wherein CDRH1, CDRH2, and CDRH3 each comprise the sequence set forth in SEQ ID NO: 19, 20, or 21, with 0-3 amino acid modifications; and (b) a light chain comprising a light chain variable region (LCVR), wherein the LCVR comprises light chain complementarity determining region 1 (CDRL1), CDRL2, and CDRL3, wherein CDRL1, CDRL2, and CDRL3 each comprise the sequence set forth in SEQ ID NO: 22, 23, or 24, with 0-3 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 set forth 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 set forth in SEQ ID NO: 17 with 0-10 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 set forth in SEQ ID NO: 17 with 0-9 amino acid modifications. In some embodiments, the HCVR comprises an amino acid sequence set forth in SEQ ID NO: 17 with 0-8 amino acid modifications. In some embodiments, the HCVR comprises an amino acid sequence set forth in SEQ ID NO: 17 with 0-7 amino acid modifications. In some embodiments, the HCVR comprises an amino acid sequence set forth in SEQ ID NO: 17 with 0-6 amino acid modifications. In some embodiments, the HCVR comprises an amino acid sequence set forth in SEQ ID NO: 17 with 0-5 amino acid modifications. In some embodiments, the HCVR comprises an amino acid sequence set forth in SEQ ID NO: 17 with 0-4 amino acid modifications. In some embodiments, the HCVR comprises an amino acid sequence set forth in SEQ ID NO: 17 with 0-3 amino acid modifications. In some embodiments, the HCVR comprises an amino acid sequence set forth in SEQ ID NO: 17 with 0-2 amino acid modifications. In some embodiments, the HCVR comprises an amino acid sequence set forth in SEQ ID NO: 17 with 0-1 amino acid modifications. In some embodiments, the HCVR comprises an amino acid sequence set forth in SEQ ID NO: 17. In some embodiments, the LCVR comprises an amino acid sequence set forth in SEQ ID NO: 18 with 0-10 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 an amino acid sequence set forth in SEQ ID NO: 18 with 0-9 amino acid modifications.In some embodiments, the LCVR comprises an amino acid sequence set forth in SEQ ID NO: 18 with 0 to 8 amino acid modifications. In some embodiments, the LCVR comprises an amino acid sequence set forth in SEQ ID NO: 18 with 0 to 7 amino acid modifications. In some embodiments, the LCVR comprises an amino acid sequence set forth in SEQ ID NO: 18 with 0 to 6 amino acid modifications. In some embodiments, the LCVR comprises an amino acid sequence set forth in SEQ ID NO: 18 with 0 to 5 amino acid modifications. In some embodiments, the LCVR comprises an amino acid sequence set forth in SEQ ID NO: 18 with 0 to 4 amino acid modifications. In some embodiments, the LCVR comprises an amino acid sequence set forth in SEQ ID NO: 18 with 0 to 3 amino acid modifications. In some embodiments, the LCVR comprises an amino acid sequence set forth in SEQ ID NO: 18 with 0 to 2 amino acid modifications. In some embodiments, the LCVR comprises an amino acid sequence set forth in SEQ ID NO: 18 with 0 to 1 amino acid modifications. In some embodiments, the LCVR comprises an amino acid sequence set forth in SEQ ID NO: 18.

[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 heavy chain complementarity determining region 1 (CDRH1), CDRH2, and CDRH3, wherein CDRH1, CDRH2, and CDRH3 each comprise the sequence set forth in SEQ ID NO: 27, 28, or 29, with 0-3 amino acid modifications; and (b) a light chain comprising a light chain variable region (LCVR), wherein the LCVR comprises light chain complementarity determining region 1 (CDRL1), CDRL2, and CDRL3, wherein CDRL1, CDRL2, and CDRL3 each comprise the sequence set forth in SEQ ID NO: 30, 31, or 32, with 0-3 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 set forth 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 set forth in SEQ ID NO: 25 with 0-10 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 set forth in SEQ ID NO: 25 with 0-9 amino acid modifications. In some embodiments, the HCVR comprises an amino acid sequence set forth in SEQ ID NO: 25 with 0-8 amino acid modifications. In some embodiments, the HCVR comprises an amino acid sequence set forth in SEQ ID NO: 25 with 0-7 amino acid modifications. In some embodiments, the HCVR comprises an amino acid sequence set forth in SEQ ID NO: 25 with 0-6 amino acid modifications. In some embodiments, the HCVR comprises an amino acid sequence set forth in SEQ ID NO: 25 with 0-5 amino acid modifications. In some embodiments, the HCVR comprises an amino acid sequence set forth in SEQ ID NO: 25 with 0-4 amino acid modifications. In some embodiments, the HCVR comprises an amino acid sequence set forth in SEQ ID NO: 25 with 0-3 amino acid modifications. In some embodiments, the HCVR comprises an amino acid sequence set forth in SEQ ID NO: 25 with 0-2 amino acid modifications. In some embodiments, the HCVR comprises an amino acid sequence set forth in SEQ ID NO: 25 with 0-1 amino acid modifications. In some embodiments, the HCVR comprises an amino acid sequence set forth in SEQ ID NO: 25. In some embodiments, the LCVR comprises an amino acid sequence set forth in SEQ ID NO: 26 with 0-10 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 an amino acid sequence set forth in SEQ ID NO: 26 with 0-9 amino acid modifications.In some embodiments, the LCVR comprises an amino acid sequence set forth in SEQ ID NO: 26 with 0 to 8 amino acid modifications. In some embodiments, the LCVR comprises an amino acid sequence set forth in SEQ ID NO: 26 with 0 to 7 amino acid modifications. In some embodiments, the LCVR comprises an amino acid sequence set forth in SEQ ID NO: 26 with 0 to 6 amino acid modifications. In some embodiments, the LCVR comprises an amino acid sequence set forth in SEQ ID NO: 26 with 0 to 5 amino acid modifications. In some embodiments, the LCVR comprises an amino acid sequence set forth in SEQ ID NO: 26 with 0 to 4 amino acid modifications. In some embodiments, the LCVR comprises an amino acid sequence set forth in SEQ ID NO: 26 with 0 to 3 amino acid modifications. In some embodiments, the LCVR comprises an amino acid sequence set forth in SEQ ID NO: 26 with 0 to 2 amino acid modifications. In some embodiments, the LCVR comprises an amino acid sequence set forth in SEQ ID NO: 26 with 0 to 1 amino acid modification. In some embodiments, the LCVR comprises an amino acid sequence set forth in SEQ ID NO: 26.

[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 heavy chain complementarity determining region 1 (CDRH1), CDRH2, and CDRH3, wherein CDRH1, CDRH2, and CDRH3 each comprise a sequence set forth in SEQ ID NO: 35, 36, or 37, with 0-3 amino acid modifications; and (b) a light chain comprising a light chain variable region (LCVR), wherein the LCVR comprises light chain complementarity determining region 1 (CDRL1), CDRL2, and CDRL3, wherein CDRL1, CDRL2, and CDRL3 each comprise a sequence set forth in SEQ ID NO: 38, 39, or 40, with 0-3 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 set forth 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 set forth in SEQ ID NO: 33 with 0-10 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 set forth in SEQ ID NO: 33 with 0-9 amino acid modifications. In some embodiments, the HCVR comprises an amino acid sequence set forth in SEQ ID NO: 33 with 0-8 amino acid modifications. In some embodiments, the HCVR comprises an amino acid sequence set forth in SEQ ID NO: 33 with 0-7 amino acid modifications. In some embodiments, the HCVR comprises an amino acid sequence set forth in SEQ ID NO: 33 with 0-6 amino acid modifications. In some embodiments, the HCVR comprises an amino acid sequence set forth in SEQ ID NO: 33 with 0-5 amino acid modifications. In some embodiments, the HCVR comprises an amino acid sequence set forth in SEQ ID NO: 33 with 0-4 amino acid modifications. In some embodiments, the HCVR comprises an amino acid sequence set forth in SEQ ID NO: 33 with 0-3 amino acid modifications. In some embodiments, the HCVR comprises an amino acid sequence set forth in SEQ ID NO: 33 with 0-2 amino acid modifications. In some embodiments, the HCVR comprises an amino acid sequence set forth in SEQ ID NO: 33 with 0-1 amino acid modifications. In some embodiments, the HCVR comprises an amino acid sequence set forth in SEQ ID NO: 33. In some embodiments, the LCVR comprises an amino acid sequence set forth in SEQ ID NO: 34 with 0-10 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 an amino acid sequence set forth in SEQ ID NO: 34 with 0-9 amino acid modifications.In some embodiments, the LCVR comprises an amino acid sequence set forth in SEQ ID NO: 34 with 0 to 8 amino acid modifications. In some embodiments, the LCVR comprises an amino acid sequence set forth in SEQ ID NO: 34 with 0 to 7 amino acid modifications. In some embodiments, the LCVR comprises an amino acid sequence set forth in SEQ ID NO: 34 with 0 to 6 amino acid modifications. In some embodiments, the LCVR comprises an amino acid sequence set forth in SEQ ID NO: 34 with 0 to 5 amino acid modifications. In some embodiments, the LCVR comprises an amino acid sequence set forth in SEQ ID NO: 34 with 0 to 4 amino acid modifications. In some embodiments, the LCVR comprises an amino acid sequence set forth in SEQ ID NO: 34 with 0 to 3 amino acid modifications. In some embodiments, the LCVR comprises an amino acid sequence set forth in SEQ ID NO: 34 with 0 to 2 amino acid modifications. In some embodiments, the LCVR comprises an amino acid sequence set forth in SEQ ID NO: 34 with 0 to 1 amino acid modification. In some embodiments, the LCVR comprises an amino acid sequence set forth in SEQ ID NO: 34.

[0036] 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.

[0037] In some embodiments, the light chain variable region is linked to a light chain constant region comprising the amino acid sequence set forth in SEQ ID NO: 62 with 0-10 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 linked to a light chain constant region comprising the amino acid sequence set forth in SEQ ID NO: 62 with 0-9 amino acid modifications. In some embodiments, the light chain variable region is linked to a light chain constant region comprising the amino acid sequence set forth in SEQ ID NO: 62 with 0-8 amino acid modifications. In some embodiments, the light chain variable region is linked to a light chain constant region comprising the amino acid sequence set forth in SEQ ID NO: 62 with 0-7 amino acid modifications. In some embodiments, the light chain variable region is linked to a light chain constant region comprising the amino acid sequence set forth in SEQ ID NO: 62 with 0-6 amino acid modifications. In some embodiments, the light chain variable region is linked to a light chain constant region comprising the amino acid sequence set forth in SEQ ID NO: 62 with 0-5 amino acid modifications. In some embodiments, the light chain variable region is linked to a light chain constant region comprising the amino acid sequence set forth in SEQ ID NO: 62 with 0-4 amino acid modifications. In some embodiments, the light chain variable region is linked to a light chain constant region comprising the amino acid sequence set forth in SEQ ID NO: 62 with 0-3 amino acid modifications. In some embodiments, the light chain variable region is linked to a light chain constant region comprising the amino acid sequence set forth in SEQ ID NO: 62 with 0-2 amino acid modifications. In some embodiments, the light chain variable region is linked to a light chain constant region comprising the amino acid sequence set forth in SEQ ID NO: 62 with 0-1 amino acid modifications. In some embodiments, the light chain variable region is linked to a light chain constant region comprising the amino acid sequence set forth in SEQ ID NO: 62.

[0038] 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 set forth 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 at least 95% sequence identity to the amino acid sequence set forth 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 at least 97% sequence identity to the amino acid sequence set forth 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 at least 98% sequence identity to the amino acid sequence set forth 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 at least 99% sequence identity to the amino acid sequence set forth 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 set forth in SEQ ID NO:64.

[0039] In some embodiments, the light chain variable region is linked to a light chain constant region comprising the amino acid sequence set forth in SEQ ID NO: 64 with 0-10 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 linked to a light chain constant region comprising the amino acid sequence set forth in SEQ ID NO: 64 with 0-9 amino acid modifications. In some embodiments, the light chain variable region is linked to a light chain constant region comprising the amino acid sequence set forth in SEQ ID NO: 64 with 0-8 amino acid modifications. In some embodiments, the light chain variable region is linked to a light chain constant region comprising the amino acid sequence set forth in SEQ ID NO: 64 with 0-7 amino acid modifications. In some embodiments, the light chain variable region is linked to a light chain constant region comprising the amino acid sequence set forth in SEQ ID NO: 64 with 0-6 amino acid modifications. In some embodiments, the light chain variable region is linked to a light chain constant region comprising the amino acid sequence set forth in SEQ ID NO: 64 with 0-5 amino acid modifications. In some embodiments, the light chain variable region is linked to a light chain constant region comprising the amino acid sequence set forth in SEQ ID NO: 64 with 0-4 amino acid modifications. In some embodiments, the light chain variable region is linked to a light chain constant region comprising the amino acid sequence set forth in SEQ ID NO: 64 with 0-3 amino acid modifications. In some embodiments, the light chain variable region is linked to a light chain constant region comprising the amino acid sequence set forth in SEQ ID NO: 64 with 0-2 amino acid modifications. In some embodiments, the light chain variable region is linked to a light chain constant region comprising the amino acid sequence set forth in SEQ ID NO: 64 with 0-1 amino acid modifications. In some embodiments, the light chain variable region is linked to a light chain constant region comprising the amino acid sequence set forth in SEQ ID NO: 64.

[0040] In some embodiments, the heavy chain constant region comprises an amino acid sequence having at least 90% sequence identity to the amino acid sequence set forth in SEQ ID NO:61. In some embodiments, the heavy chain constant region comprises an amino acid sequence having at least 95% sequence identity to the amino acid sequence set forth in SEQ ID NO:61. In some embodiments, the heavy chain constant region comprises an amino acid sequence having at least 97% sequence identity to the amino acid sequence set forth in SEQ ID NO:61. In some embodiments, the heavy chain constant region comprises an amino acid sequence having at least 98% sequence identity to the amino acid sequence set forth in SEQ ID NO:61. In some embodiments, the heavy chain constant region comprises an amino acid sequence having at least 99% sequence identity to the amino acid sequence set forth in SEQ ID NO:61. In some embodiments, the heavy chain constant region comprises an amino acid sequence having 100% sequence identity to the amino acid sequence set forth in SEQ ID NO:61. In some embodiments, the HCVR is linked to a heavy chain constant region comprising an amino acid sequence set forth in SEQ ID NO:61 with 0-10 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 the amino acid sequence set forth in SEQ ID NO: 61 with 0 to 9 amino acid modifications. In some embodiments, the heavy chain constant region comprises the amino acid sequence set forth in SEQ ID NO: 61 with 0 to 8 amino acid modifications. In some embodiments, the heavy chain constant region comprises the amino acid sequence set forth in SEQ ID NO: 61 with 0 to 7 amino acid modifications. In some embodiments, the heavy chain constant region comprises the amino acid sequence set forth in SEQ ID NO: 61 with 0 to 6 amino acid modifications. In some embodiments, the heavy chain constant region comprises the amino acid sequence set forth in SEQ ID NO: 61 with 0 to 5 amino acid modifications. In some embodiments, the heavy chain constant region comprises the amino acid sequence set forth in SEQ ID NO: 61 with 0 to 4 amino acid modifications. In some embodiments, the heavy chain constant region comprises the amino acid sequence set forth in SEQ ID NO: 61 with 0 to 3 amino acid modifications. In some embodiments, the heavy chain constant region comprises the amino acid sequence set forth in SEQ ID NO: 61 with 0 to 2 amino acid modifications.In some embodiments, the heavy chain constant region comprises the amino acid sequence set forth in SEQ ID NO: 61 with 0 to 1 amino acid modifications. In some embodiments, the heavy chain constant region comprises the amino acid sequence set forth in SEQ ID NO: 61.

[0041] 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 light chain constant region comprising an amino acid sequence having 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 set forth in SEQ ID NO: 63 with 0-10 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 set forth in SEQ ID NO: 63 with 0-9 amino acid modifications. In some embodiments, the HCVR is linked to a heavy chain constant region comprising an amino acid sequence set forth in SEQ ID NO: 63 with 0-8 amino acid modifications. In some embodiments, the HCVR is linked to a heavy chain constant region comprising an amino acid sequence set forth in SEQ ID NO: 63 with 0-7 amino acid modifications. In some embodiments, the HCVR is linked to a heavy chain constant region comprising an amino acid sequence set forth in SEQ ID NO: 63 with 0-6 amino acid modifications. In some embodiments, the HCVR is linked to a heavy chain constant region comprising an amino acid sequence set forth in SEQ ID NO: 63 with 0-5 amino acid modifications.In some embodiments, the HCVR is linked to a heavy chain constant region comprising the amino acid sequence set forth in SEQ ID NO: 63 with 0-4 amino acid modifications. In some embodiments, the HCVR is linked to a heavy chain constant region comprising the amino acid sequence set forth in SEQ ID NO: 63 with 0-3 amino acid modifications. In some embodiments, the HCVR is linked to a heavy chain constant region comprising the amino acid sequence set forth in SEQ ID NO: 63 with 0-2 amino acid modifications. In some embodiments, the HCVR is linked to a heavy chain constant region comprising the amino acid sequence set forth in SEQ ID NO: 63 with 0-1 amino acid modifications. In some embodiments, the HCVR is linked to a heavy chain constant region comprising the amino acid sequence set forth in SEQ ID NO: 63.

[0042] 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 light chain constant region comprising an amino acid sequence having 100% sequence identity to the amino acid sequence set forth in SEQ ID NO: 75. In some embodiments, the heavy chain constant region comprises the amino acid sequence set forth 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 the amino acid sequence set forth in SEQ ID NO: 75 with 0 to 9 amino acid modifications. In some embodiments, the heavy chain constant region comprises the amino acid sequence set forth in SEQ ID NO: 75 with 0 to 8 amino acid modifications. In some embodiments, the heavy chain constant region comprises the amino acid sequence set forth in SEQ ID NO: 75 with 0 to 7 amino acid modifications. In some embodiments, the heavy chain constant region comprises the amino acid sequence set forth in SEQ ID NO: 75 with 0 to 6 amino acid modifications. In some embodiments, the heavy chain constant region comprises the amino acid sequence set forth in SEQ ID NO: 75 with 0 to 5 amino acid modifications. In some embodiments, the heavy chain constant region comprises the amino acid sequence set forth in SEQ ID NO: 75 with 0 to 4 amino acid modifications. In some embodiments, the heavy chain constant region comprises the amino acid sequence set forth in SEQ ID NO: 75 with 0 to 3 amino acid modifications.In some embodiments, the heavy chain constant region comprises the amino acid sequence set forth in SEQ ID NO: 75 with 0 to 2 amino acid modifications. In some embodiments, the heavy chain constant region comprises the amino acid sequence set forth in SEQ ID NO: 75 with 0 to 1 amino acid modifications. In some embodiments, the heavy chain constant region comprises the amino acid sequence set forth in SEQ ID NO: 75.

[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: 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 light chain constant region comprising an amino acid sequence having 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 set forth in SEQ ID NO: 76 with 0-10 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 set forth in SEQ ID NO: 76 with 0-9 amino acid modifications. In some embodiments, the HCVR is linked to a heavy chain constant region comprising an amino acid sequence set forth in SEQ ID NO: 76 with 0-8 amino acid modifications. In some embodiments, the HCVR is linked to a heavy chain constant region comprising an amino acid sequence set forth in SEQ ID NO: 76 with 0-7 amino acid modifications. In some embodiments, the HCVR is linked to a heavy chain constant region comprising an amino acid sequence set forth in SEQ ID NO: 76 with 0-6 amino acid modifications. In some embodiments, the HCVR is linked to a heavy chain constant region comprising an amino acid sequence set forth in SEQ ID NO: 76 with 0-5 amino acid modifications.In some embodiments, the HCVR is linked to a heavy chain constant region comprising the amino acid sequence set forth in SEQ ID NO: 76 with 0-4 amino acid modifications. In some embodiments, the HCVR is linked to a heavy chain constant region comprising the amino acid sequence set forth in SEQ ID NO: 76 with 0-3 amino acid modifications. In some embodiments, the HCVR is linked to a heavy chain constant region comprising the amino acid sequence set forth in SEQ ID NO: 76 with 0-2 amino acid modifications. In some embodiments, the HCVR is linked to a heavy chain constant region comprising the amino acid sequence set forth in SEQ ID NO: 76 with 0-1 amino acid modifications. In some embodiments, the HCVR is linked to a heavy chain constant region comprising the amino acid sequence set forth in SEQ ID NO: 76.

[0044] In some embodiments, the HCVR is linked to a heavy chain constant region, which 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 an aspartic acid (D) at position 238 (EU index).

[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: 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 light chain constant region comprising an amino acid sequence having 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 set forth in SEQ ID NO: 77 with 0-10 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 set forth in SEQ ID NO: 77 with 0-9 amino acid modifications. In some embodiments, the HCVR is linked to a heavy chain constant region comprising an amino acid sequence set forth in SEQ ID NO: 77 with 0-8 amino acid modifications. In some embodiments, the HCVR is linked to a heavy chain constant region comprising an amino acid sequence set forth in SEQ ID NO: 77 with 0-7 amino acid modifications. In some embodiments, the HCVR is linked to a heavy chain constant region comprising an amino acid sequence set forth in SEQ ID NO: 77 with 0-6 amino acid modifications. In some embodiments, the HCVR is linked to a heavy chain constant region comprising an amino acid sequence set forth in SEQ ID NO: 77 with 0-5 amino acid modifications.In some embodiments, the HCVR is linked to a heavy chain constant region comprising an amino acid sequence set forth in SEQ ID NO: 77 with 0-4 amino acid modifications. In some embodiments, the HCVR is linked to a heavy chain constant region comprising an amino acid sequence set forth in SEQ ID NO: 77 with 0-3 amino acid modifications. In some embodiments, the HCVR is linked to a heavy chain constant region comprising an amino acid sequence set forth in SEQ ID NO: 77 with 0-2 amino acid modifications. In some embodiments, the HCVR is linked to a heavy chain constant region comprising an amino acid sequence set forth in SEQ ID NO: 77 with 0-1 amino acid modifications. In some embodiments, the HCVR is linked to a heavy chain constant region comprising an amino acid sequence set forth in SEQ ID NO: 77. In some embodiments, the X at position 121 of SEQ ID NO: 77 is D. In some embodiments, the X at position 121 of SEQ ID NO: 77 is P. In some embodiments, the X at position 329 of SEQ ID NO: 77 is G. In some embodiments, the X at position 329 of SEQ ID NO: 77 is absent. In some embodiments, the X at position 330 of SEQ ID NO: 77 is K. In some embodiments, the X at position 330 of SEQ ID NO:77 is absent.

[0046] 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 light chain constant region comprising an amino acid sequence having 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 set forth in SEQ ID NO: 78 with 0-10 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 set forth in SEQ ID NO: 78 with 0-9 amino acid modifications. In some embodiments, the HCVR is linked to a heavy chain constant region comprising an amino acid sequence set forth in SEQ ID NO: 78 with 0-8 amino acid modifications. In some embodiments, the HCVR is linked to a heavy chain constant region comprising an amino acid sequence set forth in SEQ ID NO: 78 with 0-7 amino acid modifications. In some embodiments, the HCVR is linked to a heavy chain constant region comprising an amino acid sequence set forth in SEQ ID NO: 78 with 0-6 amino acid modifications. In some embodiments, the HCVR is linked to a heavy chain constant region comprising an amino acid sequence set forth in SEQ ID NO: 78 with 0-5 amino acid modifications.In some embodiments, the HCVR is linked to a heavy chain constant region comprising the amino acid sequence set forth in SEQ ID NO: 78 with 0-4 amino acid modifications. In some embodiments, the HCVR is linked to a heavy chain constant region comprising the amino acid sequence set forth in SEQ ID NO: 78 with 0-3 amino acid modifications. In some embodiments, the HCVR is linked to a heavy chain constant region comprising the amino acid sequence set forth in SEQ ID NO: 78 with 0-2 amino acid modifications. In some embodiments, the HCVR is linked to a heavy chain constant region comprising the amino acid sequence set forth in SEQ ID NO: 78 with 0-1 amino acid modifications. In some embodiments, the HCVR is linked to a heavy chain constant region comprising the amino acid sequence set forth in SEQ ID NO: 78. In some embodiments, the X at position 108 of SEQ ID NO: 78 is S. In some embodiments, the X at position 108 of SEQ ID NO: 78 is P. In some embodiments, the X at position 326 of SEQ ID NO: 78 is G. In some embodiments, the X at position 326 of SEQ ID NO: 78 is absent. In some embodiments, the X at position 327 of SEQ ID NO: 78 is K. In some embodiments, the X at position 327 of SEQ ID NO:78 is absent.

[0047] 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.

[0048] In some cases, the antibody or antigen-binding fragment thereof binds to a region of 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.

[0049] In some cases, the antibody or antigen-binding fragment thereof binds to a region of 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.

[0050] In some cases, the antibody or antigen-binding fragment thereof binds to a region up to 100 Å, 90 Å, 80 Å, 70 Å, 60 Å, 50 Å, 40 Å, 30 Å, 20 Å, or 10 Å from the cell membrane when the antibody or antigen-binding fragment thereof binds to a CD200R molecule on the cell membrane.

[0051] In some cases, the antibody or antigen-binding fragment thereof binds to a region about 100 Å, 90 Å, 80 Å, 70 Å, 60 Å, 50 Å, 40 Å, 30 Å, 20 Å, or 10 Å from the cell membrane when the antibody or antigen-binding fragment thereof binds to a CD200R molecule on the cell membrane.

[0052] In some cases, the antibody or antigen-binding fragment thereof binds to a region proximal to the N-terminus of CD200R.

[0053] In some cases, the antibody or antigen-binding fragment thereof binds to a residue of CD200R selected from T213, E230, and S194.

[0054] In some cases, the antibody or antigen-binding fragment thereof binds to a residue of CD200R selected from T213 and E230.

[0055] In some cases, the antibody or antigen-binding fragment thereof does not bind to cynomolgus monkey CD200RLa or has a K of greater than 2 μM as determined by surface plasmon resonance (SPR) at 37° C. D It binds to cynomolgus monkey CD200RLa.

[0056] Disclosed herein, in some embodiments, is an antibody or antigen-binding fragment thereof that specifically binds to human CD200R or cynomolgus CD200R, wherein the antibody or antigen-binding fragment thereof does not bind to cynomolgus CD200RLa or has a K of greater than 2 μM as determined by surface plasmon resonance (SPR) at 37° C. D The antibody or antigen-binding fragment thereof binds to cynomolgus monkey CD200RLa.

[0057] Disclosed herein, in some aspects, are antibodies or antigen-binding fragments thereof that specifically bind to CD200R, where the antibody or antigen-binding fragment thereof binds to a region at or near the C-terminus of the extracellular portion of CD200R.

[0058] In some cases, the antibody or antigen-binding fragment thereof binds to a residue of CD200R selected from T213 and E230.

[0059] In some cases, the antibody or antigen-binding fragment thereof binds to residues T213 and E230 of CD200R.

[0060] In some cases, the antibody or antigen-binding fragment thereof is or is derived from an IgG, IgM, IgE, IgA, or IgD molecule.

[0061] In some cases, the antibody or antigen-binding fragment thereof is or is derived from an IgG1, IgG2, IgG3, or IgG4 molecule.

[0062] In some cases, the antibody is a monoclonal antibody.

[0063] In some cases, the antibody is a human or humanized antibody.

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

[0065] In some cases, the antigen-binding fragment is selected from the group consisting of an scFv, an sc(Fv)2, a dsFv, a Fab, a Fab', a (Fab')2, and a diabody.

[0066] In some cases, the antibody or antigen-binding fragment thereof comprises an Fc region.

[0067] In some cases, the Fc region comprises a modification.

[0068] In some cases, the antibody or antigen-binding fragment thereof has increased binding to FcγR2B compared to the parent molecule lacking the Fc region modification.

[0069] In some cases, the antibody or antigen-binding fragment thereof has an increased ratio of binding to FcγR2B / FcγR2A compared to the parent molecule lacking the Fc region modification.

[0070] In some cases, the Fc region comprises 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, and alanine (A) at position 297, all numbering according to the EU index.

[0071] In some cases, the heavy or light chain further comprises a constant region.

[0072] In some cases, the heavy and light chains are joined by a flexible linker to form a single chain antibody.

[0073] In some cases, the antibody or antigen-binding fragment thereof agonizes CD200R expressed on the surface of an immune cell.

[0074] In some cases, when binding to CD200R on an immune cell, the antibody or antigen-binding fragment thereof reduces activation of the immune cell relative to a comparable immune cell to which the antibody or antigen-binding fragment thereof is not bound.

[0075] In some cases, when bound to CD200R on an immune cell, the antibody or antigen-binding fragment thereof reduces proliferation of the immune cell relative to a comparable immune cell to which the antibody or antigen-binding fragment thereof is not bound.

[0076] In some cases, the reduction in immune cell activation or proliferation is measured by an assay described in Examples 5, 16, or 17.

[0077] In some cases, the decrease in cell proliferation or activation is measured in vitro or in vivo.

[0078] In some cases, the decrease in cell proliferation or activation is at least about 10%, 15%, 20%, 25%, 30%, 40%, or 50%.

[0079] In some cases, the decrease 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%.

[0080] In some cases, when binding to CD200R on an immune cell, the antibody or antigen-binding fragment thereof reduces expression of inflammatory genes in the immune cell relative to a comparable immune cell to which the antibody or antigen-binding fragment thereof is not bound.

[0081] 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 in the immune cell relative to a comparable immune cell to which the antibody, or antigen-binding fragment thereof, is not bound.

[0082] In some cases, the decrease in NFκB signaling in an immune cell is measured by the assay described in Example 5.

[0083] In some cases, the reduction in NFκB signaling in immune cells is at least about 10%, 15%, 20%, 25%, 30%, or 40%.

[0084] In some cases, the reduction in NFκB signaling in immune cells is about 10% to 40%, 10% to 30%, 10% to 20%, 20% to 40%, or 30% to 40%.

[0085] In some cases, the average maximum percentage inhibition of immune cell NFκB signaling induced by the antibody or antigen-binding fragment thereof is at least 20%, 30%, 40%, 50%, or 60% greater than a control antibody comprising (a) a control heavy chain comprising CDRH1, CDRH2, and CDRH3 comprising the amino acid sequences set forth in SEQ ID NOs: 55-57, respectively, and (b) a control light chain comprising CDRL1, CDRL2, and CDRL3 comprising the amino acid sequences set forth in SEQ ID NOs: 58-60, respectively.

[0086] In some cases, the average maximum percentage inhibition of NFκB signaling in immune cells induced by the antibody or antigen-binding fragment thereof is at least 20%, 30%, 40%, 50%, or 60% greater than a control antibody comprising a control heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO:53 and a control light chain variable region comprising the amino acid sequence set forth in SEQ ID NO:54.

[0087] In some cases, the immune cell is a T cell or a monocyte.

[0088] In some cases, the antibody or antigen-binding fragment thereof inhibits activation of basophils.

[0089] In some cases, the antibody or antigen-binding fragment thereof inhibits FcεRI-induced basophil activation.

[0090] In some cases, the antibody or antigen-binding fragment thereof inhibits basophil activation induced by binding of IgE to basophils.

[0091] In some cases, the antibody or antigen-binding fragment thereof inhibits basophil activation by at least 40% or at least 50%.

[0092] In some cases, the antibody or antigen-binding fragment thereof inhibits basophil activation by about 10% to about 90%, about 20% to about 70%, about 30% to about 60%, or about 40% to about 60%.

[0093] In some cases, the antibody or antigen-binding fragment thereof inhibits basophil activation by about 10%, 20%, 30%, 40%, 45%, 50%, 55%, 60%, 70%, 80%, or 90%. In some cases, inhibition of basophil activation is measured in an assay described in Example 10.

[0094] In some cases, the antibody or antigen-binding fragment thereof does not inhibit binding of CD200 to CD200R.

[0095] In some cases, the antibody or antigen-binding fragment thereof has a K of less than 10 nM as determined by surface plasmon resonance (SPR) at 37°C. D It binds to human CD200R.

[0096] In some cases, the antibody or antigen-binding fragment thereof has a K of less than 5 nM as determined by surface plasmon resonance (SPR) at 37°C. D It binds to human CD200R.

[0097] In some cases, the antibody or antigen-binding fragment thereof has a K of less than 2 nM as determined by surface plasmon resonance (SPR) at 37°C. D It binds to human CD200R.

[0098] In some cases, the antibody or antigen-binding fragment thereof has a K of less than 1 nM as determined by surface plasmon resonance (SPR) at 37°C. D It binds to human CD200R.

[0099] In some cases, the antibody or antigen-binding fragment thereof has a K of less than 0.5 nM as determined by surface plasmon resonance (SPR) at 37°C. D It binds to human CD200R.

[0100] In some cases, the antibody or antigen-binding fragment thereof has a K of less than 100 nM as determined by surface plasmon resonance (SPR) at 37°C. D It binds to cynomolgus monkey CD200R.

[0101] In some cases, the antibody or antigen-binding fragment thereof has a K of less than 1 nM as determined by surface plasmon resonance (SPR) at 37°C. D It binds to cynomolgus monkey CD200R.

[0102] In some cases, the antibody or antigen-binding fragment thereof has a K of less than 0.1 nM as determined by surface plasmon resonance (SPR) at 37°C. D It binds to cynomolgus monkey CD200R.

[0103] In some cases, the antibody or antigen-binding fragment thereof has a K of less than 0.01 nM as determined by surface plasmon resonance (SPR) at 37°C. D It binds to cynomolgus monkey CD200R.

[0104] In some cases, when an 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.

[0105] In some cases, the antibody or antigen-binding fragment thereof comprises a domain that binds to an Fc receptor.

[0106] In some cases, the Fc receptor is expressed on the surface of an immune cell.

[0107] In some cases, the immune cell is an antigen-presenting cell.

[0108] In some cases, the antigen-presenting cell is a dendritic cell, a macrophage, a monocyte, or a neutrophil.

[0109] In some cases, binding of the antibody or antigen-binding fragment thereof to an Fc receptor expressed on the surface of an immune cell and binding to CD200R on the surface of a second immune cell brings the cell surface of the immune cell and the cell surface of the second immune cell within 250 Å, 200 Å, 150 Å, or 100 Å.

[0110] In some cases, binding of the antibody or antigen-binding fragment thereof to an Fc receptor expressed on the surface of an immune cell and binding to CD200R on the surface of a second immune cell brings the cell surface of the immune cell and the cell surface of the second immune cell within 250 Å, 200 Å, 150 Å, or 100 Å.

[0111] In some cases, the Fc receptor is FcγRIIB.

[0112] In some cases, the antibody or antigen-binding fragment thereof is bispecific or multispecific.

[0113] Disclosed herein, in some aspects, 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.

[0114] Disclosed herein, in some aspects, are vectors that include one or more nucleotide sequences encoding a polypeptide capable of forming an antibody or antigen-binding fragment thereof disclosed herein.

[0115] Disclosed herein, in some aspects, are host cells that contain one or more nucleic acid molecules encoding heavy and light chain amino acid sequences that, when expressed, can form an antibody or antigen-binding fragment thereof disclosed herein.

[0116] Disclosed herein, in some aspects, are methods that include culturing a host cell disclosed herein under conditions for the production of an antibody or antigen-binding fragment thereof.

[0117] Disclosed herein, in some aspects, is a method for producing a medicament for use in a method for treating a medicament for which:

[0118] (a) providing a host cell containing one or more nucleic acid molecules encoding heavy and light chain amino acid sequences that, when expressed, are capable of forming an antibody or antigen-binding fragment thereof disclosed herein;

[0119] (b) culturing a host cell that expresses the encoded amino acid sequence; and

[0120] (c) isolating the antibody or antigen-binding fragment thereof.

[0121] Disclosed herein, in some aspects, is an immunoconjugate comprising an antibody or antigen-binding fragment thereof disclosed herein conjugated to an agent.

[0122] Disclosed herein, in some aspects, 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 pharma- ceutically acceptable excipient.

[0123] Disclosed herein, in some aspects, is an antibody or antigen-binding fragment thereof disclosed herein, or an immunoconjugate disclosed herein, or a pharmaceutical composition disclosed herein, for use in therapy.

[0124] Disclosed herein, in some aspects, is a kit comprising, in a container, an antibody or antigen-binding fragment thereof disclosed herein, an immunoconjugate disclosed herein, or a pharmaceutical composition disclosed herein.

[0125] In some cases, the kit further comprises informational material containing instructions for use of the antibody or antigen-binding fragment thereof disclosed herein, the immunoconjugate disclosed herein, or the pharmaceutical composition disclosed herein.

[0126] Disclosed herein, in some aspects, is a method of treating a disease or condition in a subject in need thereof, 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 a pharmaceutical composition disclosed herein.

[0127] In some cases, the disease or condition comprises a CD200R-associated disease or condition.

[0128] In some cases, the disease or condition comprises an autoimmune disease or condition, or an inflammatory disease or condition.

[0129] In some cases, the disease or condition is acute disseminated encephalomyelitis (ADEM), Addison's disease, allergies, alopecia areata, amyotrophic lateral sclerosis, ankylosing spondylitis, antiphospholipid syndrome, asthma, autoimmune hemolytic anemia, autoimmune hepatitis, autoimmune pancreatitis, autoimmune polyendocrine syndrome, Behcet's disease, bullous pemphigoid, cerebral malaria, chronic inflammatory demyelinating polyneuropathy, 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, hidradenitis suppurativa, inflammatory bowel disease, inflammatory bowel disease, inflammatory bowel syndrome, inflammatory bowel disease ... 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 cyst disease, polymyositis, primary cholangitis, primary sclerosing cholangitis, psoriasis, psoriatic arthritis, rheumatoid arthritis, sarcoidosis, Sjogren's syndrome, systemic lupus erythematosus, Takayasu's arteritis, temporal arteritis, transplant rejection, transverse myelitis, ulcerative colitis, uveitis, vasculitis, vitiligo, and Vogt-Koyanagi-Harada disease.

[0130] In some cases, the disease or condition comprises an autoimmune skin disease.

[0131] In some cases, the autoimmune skin disease or condition includes 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.

[0132] In some cases, the subject is a human subject.

[0133] Disclosed herein, in some aspects, is a method of downregulating an immune response in a subject, comprising administering to the subject an antibody or antigen-binding fragment thereof, or an immunoconjugate disclosed herein, or administering to the subject a pharmaceutical composition disclosed herein.

[0134] Disclosed herein, in some aspects, is a method of inhibiting an immune cell that expresses CD200R, comprising contacting the immune cell with an antibody or antigen-binding fragment thereof disclosed herein, or an immunoconjugate disclosed herein.

[0135] In some cases, the immune cell comprises a T cell, a B cell, or a macrophage.

[0136] In some cases, the immune cells include antigen-specific T cells.

[0137] In some cases, the subject is a human subject.

[0138] Incorporation by Reference 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]

[0139] The novel features of the present disclosure are set forth with particularity in the appended claims. A better understanding of the features and advantages of the present disclosure will be obtained by reference to the following detailed description that sets forth illustrative embodiments, in which the principles of the disclosure are utilized, and the accompanying drawings.

[0140] [Figure 1A] Shown are surface plasmon resonance (SPR) curves showing binding of CD200 by CD200R injected over and captured by immobilized anti-CD200R antibodies for a non-competing clone (FIG. 1A) and a competing clone (FIG. 1B), respectively. In the case of the non-competing clone (illustrated in FIG. 1A), CD200R captured by the non-competing CD200R antibody is able to bind to its natural ligand CD200, and therefore shows an increase in the SPR signal on the graph, whereas in the case of the competing clone (illustrated in FIG. 1B), CD200R captured by the competing CD200R antibody is unable to bind to its natural ligand CD200, and therefore there is no significant change in the SPR signal on the graph. [Figure 1B] Shown are surface plasmon resonance (SPR) curves showing binding of CD200 by CD200R injected over and captured by immobilized anti-CD200R antibodies for a non-competing clone (FIG. 1A) and a competing clone (FIG. 1B), respectively. In the case of the non-competing clone (illustrated in FIG. 1A), CD200R captured by the non-competing CD200R antibody is able to bind to its natural ligand CD200, and therefore shows an increase in the SPR signal on the graph, whereas in the case of the competing clone (illustrated in FIG. 1B), CD200R captured by the competing CD200R antibody is unable to bind to its natural ligand CD200, and therefore there is no significant change in the SPR signal on the graph.

[0141] [Diagram 2]Figure 1 shows the epitope map of clone 21.3.1 defined by surface mutagenesis. Mutated surface residues that reduced antibody binding to the wild type receptor by more than 90% are indicated by residue numbers (E230 and T213), while mutated surface residues that did not affect antibody binding are shaded but not indicated by residue numbers. The epitope was found to be near the C-terminus of CD200R, very close to the likely location of the cell membrane. As shown, the orientation of the receptor with respect to the cell membrane is predicted by placing the C-terminus of the extracellular portion proximal to the membrane and the N-terminus distal to the membrane.

[0142] [Diagram 3] 1 shows the alignment of exemplary humanized VH and VL variants to the murine parental clone 21.3.1 variable domain sequences.

[0143] [Figure 4A] 1 shows predicted immunogenicity based on HLA-DR binding scores for the mouse parent variable domain and exemplary humanized variable domains of clone 21.3.1. [Figure 4B] 1 shows predicted immunogenicity based on HLA-DR binding scores for the mouse parent variable domain and exemplary humanized variable domains of clone 21.3.1. [Figure 4C] 1 shows predicted immunogenicity based on HLA-DR binding scores for the mouse parent variable domain and exemplary humanized variable domains of clone 21.3.1. [Figure 4D] 1 shows predicted immunogenicity based on HLA-DR binding scores for the mouse parent variable domain and exemplary humanized variable domains of clone 21.3.1.

[0144] [Figure 5A]Inhibition of FcεRI-induced basophil activation. Figure 5A is a schematic of the experiment. Figure 5B shows images of basophils from an individual donor 30 min after IgE stimulation. Figures 5C-5D show plots quantifying basophil activation, expressed as the count of CD63+ cells (light grey objects in Figure 5B) divided by the total cell count (phase object in Figure 5B). Results for individual donors are plotted in Figure 5C. Normalized AUCs are summarized in Figure 5D. [Figure 5B] Inhibition of FcεRI-induced basophil activation. Figure 5A is a schematic of the experiment. Figure 5B shows images of basophils from an individual donor 30 min after IgE stimulation. Figures 5C-5D show plots quantifying basophil activation, expressed as the count of CD63+ cells (light grey objects in Figure 5B) divided by the total cell count (phase object in Figure 5B). Results for individual donors are plotted in Figure 5C. Normalized AUCs are summarized in Figure 5D. [Figure 5C] Inhibition of FcεRI-induced basophil activation. Figure 5A is a schematic of the experiment. Figure 5B shows images of basophils from an individual donor 30 min after IgE stimulation. Figures 5C-5D show plots quantifying basophil activation, expressed as the count of CD63+ cells (light grey objects in Figure 5B) divided by the total cell count (phase object in Figure 5B). Results for individual donors are plotted in Figure 5C. Normalized AUCs are summarized in Figure 5D. [Figure 5D] Inhibition of FcεRI-induced basophil activation. Figure 5A is a schematic of the experiment. Figure 5B shows images of basophils from an individual donor 30 min after IgE stimulation. Figures 5C-5D show plots quantifying basophil activation, expressed as the count of CD63+ cells (light grey objects in Figure 5B) divided by the total cell count (phase object in Figure 5B). Results for individual donors are plotted in Figure 5C. Normalized AUCs are summarized in Figure 5D.

[0145] [Figure 6A]Illustrating gene pathways regulated by CD200R signaling. Figure 6A shows results from RNA sequencing that confirmed the agonistic effect of an exemplary CD200R agonistic antibody according to some embodiments of the present disclosure, identifying 2080 differentially expressed genes (899 upregulated and 1181 downregulated) when comparing stimulated THP-1 cells in the presence of CD200R agonistic antibody versus isotype control. Figure 6B shows gene set enrichment analysis that revealed that CD200R agonism by CD200R agonistic antibody downregulated key inflammatory pathways associated with chronic inflammatory conditions. Figure 6C shows that CD200R1 is upregulated in skin biopsies from atopic dermatitis patients. [Figure 6B] Illustrating gene pathways regulated by CD200R signaling. Figure 6A shows results from RNA sequencing that confirmed the agonistic effect of an exemplary CD200R agonistic antibody according to some embodiments of the present disclosure, identifying 2080 differentially expressed genes (899 upregulated and 1181 downregulated) when comparing stimulated THP-1 cells in the presence of CD200R agonistic antibody versus isotype control. Figure 6B shows gene set enrichment analysis that revealed that CD200R agonism by CD200R agonistic antibody downregulated key inflammatory pathways associated with chronic inflammatory conditions. Figure 6C shows that CD200R1 is upregulated in skin biopsies from atopic dermatitis patients. [Figure 6C]Illustrating gene pathways regulated by CD200R signaling. Figure 6A shows results from RNA sequencing that confirmed the agonistic effect of an exemplary CD200R agonistic antibody according to some embodiments of the present disclosure, identifying 2080 differentially expressed genes (899 upregulated and 1181 downregulated) when comparing stimulated THP-1 cells in the presence of CD200R agonistic antibody versus isotype control. Figure 6B shows gene set enrichment analysis that revealed that CD200R agonism by CD200R agonistic antibody downregulated key inflammatory pathways associated with chronic inflammatory conditions. Figure 6C shows that CD200R1 is upregulated in skin biopsies from atopic dermatitis patients.

[0146] [Figure 7] Binding curves of CD200R antibodies or relevant isotype controls to human CD200R-expressing Jurkat T cells as assessed by flow cytometry.

[0147] [Figure 8] FIG. 1 shows the output of an enzyme fragment complementation assay reporting DOK2 recruitment to the cytoplasmic tail of CD200R in a Jurkat T cell line. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0148] Disclosed herein, in some aspects, are methods, compositions, kits, vectors, polynucleotides, and host cells relating to antibodies that recognize the immune cell receptor CD200R. In some embodiments, the antibodies or antigen-binding fragments thereof are agonistic antibodies. In some embodiments, the agonistic antibodies specifically bind to CD200R. In some embodiments, the agonistic antibodies specifically bind to human CD200R.

[0149] In some embodiments, agonistic anti-CD200R antibodies disclosed herein enhance or activate the CD200R signaling pathway. In some embodiments, anti-CD200R antibodies downregulate immune responses. In some embodiments, anti-CD200R antibodies downregulate inflammation. In some embodiments, anti-CD200R antibodies downregulate NF-κB signaling. In some embodiments, anti-CD200R antibodies reduce immune cell proliferation relative to comparable immune cells not bound by the anti-CD200R antibody.

[0150] 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 a signaling pathway induced by activated CD200R, for example, the interaction of Dok2 with a membrane-distal tyrosine residue located within a 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 proximity is 250 Å, 200 Å, 150 Å, or 100 Å. In some cases, the proximity of two immune cells reduces bulky phosphatase at or near the immune synapse between the two immune cells. In some embodiments, bulky phosphatase contributes to dephosphorylation of CD200R. In some embodiments, reduction of bulky phosphatase leads to more phosphorylation of CD200R, 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.

[0151] 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 monkey CD200R. In some embodiments, the anti-CD200R antibody does not compete with the natural ligand of CD200R. In some cases, the antibody binds to the C-terminus of CD200R or to a region near the C-terminus of the extracellular portion of CD200R. In some cases, the anti-CD200R antibody binds to a region near the likely location of the cell membrane. In some cases, the antibody binds to a region near the N-terminus of domain 2. When expressed on the surface of a cell membrane, CD200R can have an extracellular portion, a transmembrane portion, and an intracellular portion. When expressed on the surface, CD200R can have two IgSF domains, domain 1 and domain 2, in its extracellular portion, as described, for example, 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 more membrane proximal domain.

[0152] In other cases, the anti-CD200R antibody binds to a region more distal to the cell membrane. In some embodiments, the anti-CD200R binds to residue T213 of CD200R. In some embodiments, the anti-CD200R binds to residue E230 of CD200R. In some embodiments, the anti-CD200R binds to residues T213 and E230 of CD200R. In some embodiments, the anti-CD200R binds to residue S194 of CD200R.

[0153] In some embodiments, the disclosed CD200R agonist antibodies are more effective than existing antibodies (e.g., I-4P described in Example 5) at promoting CD200R inhibitory signaling to immune cells and / or the immune system, down-regulating immune cell responses. In some cases, the anti-CD200R antibodies disclosed herein enhance the inhibition of CD200R of the NF-κB pathway more effectively than currently existing antibodies (e.g., I-4P). The anti-CD200R antibodies disclosed herein may be particularly useful in the treatment of immune-mediated and / or CD200R-associated disorders, or diseases caused by aberrant immune pathology or having a cancerous origin.

[0154] In some embodiments, the antibody is a human antibody. In some embodiments, the CD200R antibody disclosed herein comprises 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 generated in a mouse. 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.

[0155] 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.

[0156] In some aspects, disclosed herein are compositions, systems, pharmaceutical compositions, methods of treatment, kits, and methods of manufacture related to CD200R antibodies.

[0157] It should be understood that one, some, or all of the characteristics of the various embodiments described herein may be applied to any aspect, unless the content clearly indicates otherwise. Furthermore, 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 in the following detailed description.

[0158] definition

[0159] As used herein, the terms "agonist", "agonistic", "agonize" and other grammatical synonyms refer to or relate to an agent that can bind to a receptor or any other protein target and activate or enhance the activity of the receptor or protein target or help initiate its activation. 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 change in cellular activity. As used herein, a CD200R agonist 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.

[0160] In the present disclosure, whenever an embodiment is described herein with the word "comprising," other similar embodiments are also provided that are described with the terms "consisting of" and / or "consisting essentially of." All definitions set forth herein should be construed to refer to the definitions used throughout the specification and appended claims, whether or not specifically referenced.

[0161] Throughout this specification and the appended claims, the singular forms "a," "an," and "the" include plural references unless the context clearly dictates otherwise. For example, the term "a cell" includes a plurality of cells, including mixtures thereof.

[0162] In the present disclosure, one, some, or all of the characteristics of the various embodiments described herein may be applied to any aspect, unless the content clearly indicates otherwise. Furthermore, 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 detailed description herein.

[0163] Throughout this specification and the appended claims, unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by those of ordinary skill in the art to which this disclosure pertains. For example, the Concise Dictionary of Biomedicine and Molecular Biology, Juo, Pei-Show, 2nd ed., 2002, CRC Press, The Dictionary of Cell and Molecular Biology, 3rd ed., 1999, Academic Press, and the Oxford Dictionary Of Biochemistry And Molecular Biology, Revised, 2000, Oxford University Press provide those of ordinary skill in the art with a general dictionary of many of the terms used in this disclosure.

[0164] Amino acids may be referred to herein by either their commonly known three letter symbols or the one-letter symbols recommended by the IUPAC-IUB Biochemical Nomenclature Commission. Nucleotides may likewise be referred to by their commonly accepted one-letter codes.

[0165] The numbering of amino acids in antibody variable domains, CDRs and framework regions (FRs) is according to the definition of Kabat as set forth in Kabat et al. Sequences of Proteins of Immunological Interest, 5th Ed. Public Health Service, National Institutes of Health, Bethesda, MD. (1991), unless otherwise indicated.

[0166] The term "about" or "approximately" means within an acceptable error range of a particular value as determined by one of ordinary skill in the art, which depends in part on how the value is measured or determined, i.e., the limitations of the measurement system. For example, "about" can mean within one standard deviation or more than one standard deviation, as is customary in the art. Alternatively, "about" can mean within 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 can mean within an order of magnitude, preferably within 5-fold of a value, and more preferably within 2-fold of a value. When a particular value is described in the present application and claims, unless otherwise indicated, the term "about" should be assumed to mean within an acceptable error range of the particular value.

[0167] The terms "polypeptide", "oligopeptide", "peptide" and "protein" are used interchangeably herein to refer to polymers of amino acids of any length. The polymers may be linear or branched, may comprise modified amino acids, and may be interrupted by non-amino acids. The term also encompasses amino acid polymers that are modified, either naturally or by intervention, such as disulfide bond formation, glycosylation, lipidation, acetylation, phosphorylation, or any other manipulation or modification, such as conjugation with a labeling component. Also included within the definition are, for example, polypeptides containing one or more analogs of an amino acid (including, for example, unnatural amino acids, etc.), as well as other modifications known in the art. Because the polypeptides described herein are based on antibodies, it is understood that the polypeptides can occur as single chains or associated chains.

[0168] The term "amino acid" refers to natural, unnatural, and synthetic amino acids, including, but not limited to, both the D or L optical isomers, and amino acid analogs and peptidomimetics. Amino acids are designated using standard one-letter or three-letter codes.

[0169] A "variant" as applied to a protein is a protein having sequence homology with a naturally occurring biologically active protein that retains at least a portion of the therapeutic and / or biological activity of the biologically active protein. For example, a variant protein may share at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% amino acid sequence identity, or any range between at least 70%-99%, as compared to the reference biologically active protein. As used herein, the term "biologically active protein portion" includes proteins that have been accidentally modified, for example, by site-directed mutagenesis, synthesis, insertion, or mutation of the encoding gene.

[0170] In the context of a polypeptide, a "linear sequence" or "sequence" is the order of amino acids in a polypeptide from the amino to carboxyl terminal direction in which adjacent residues in the sequence are contiguous in the primary structure of the polypeptide. A "subsequence" is a linear sequence of a portion of a polypeptide that is known to contain additional residues in one or both directions.

[0171] "Polynucleotide" or "nucleic acid," as used interchangeably herein, refers to a polymer of nucleotides of any length, including 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. Polynucleotides can contain modified nucleotides, such as methylated nucleotides and their analogs. If present, modifications to the nucleotide structure can be imparted before or after assembly of the polymer. The sequence of nucleotides can be interrupted by non-nucleotide components. A polynucleotide can be further modified after polymerization, such as by conjugation with a labeling component. Other types of modifications include, for example, "caps", substitution of one or more of the naturally occurring nucleotides with analogs, internucleotide modifications such as those with uncharged bonds (e.g., methylphosphonates, phosphotriesters, phosphoamidates, carbamates, etc.) and those with charged bonds (e.g., phosphorothioates, phosphorodithioates, etc.), those containing pendant moieties such as proteins (e.g., nucleases, toxins, antibodies, signal peptides, ply-L-lysine lysine, etc.), those containing intercalators (e.g., acridine, psoralen, etc.), those containing chelators (e.g., metals, radioactive metals, boron, metal oxides, etc.), those containing alkylators, those with modified bonds (e.g., alpha anomeric nucleic acids, etc.), and unmodified forms of polynucleotides. Additionally, any hydroxyl groups normally present in the sugar may be replaced by, for example, phosphonate groups, phosphate groups, protected by standard protecting groups, or activated to prepare additional bonds to additional nucleotides, or conjugated to a solid support. The 5' and 3' terminal OH may be phosphorylated or substituted with amines or organic capping group moieties of 1 to 20 carbon atoms. Other hydroxyls may also be derivatized to standard protecting groups.Polynucleotides may also contain analogous forms of ribose or deoxyribose sugars commonly known in the art, including, for example, 2'-O-methyl-, 2'-O-allyl, 2'-fluoro- or 2'-azido-ribose, carbocyclic sugar analogs, a-anomeric sugars, epimeric sugars such as arabinose, xylose or lyxo sugars, pyranose sugars, furanose sugars, sedoheptuloses, acyclic analogs, and non-basic nucleoside analogs such as methyl riboside. One or more phosphodiester linkages may be replaced by alternative linking groups. These alternative linking groups include phosphate, P(O)S ("thioate"), P(S)S ("dithioate"), (O)NR. 2 ("amidate"), P(O)R, P(O)OR', CO or CH 2 ("formacetal"), where each R or R' is independently H or substituted or unsubstituted alkyl (1-20C) (optionally containing an ether (-O-) linkage), aryl, alkenyl, cycloalkyl, cycloalkenyl, or araldyl. Not all linkages in a polynucleotide need be identical. The above description applies to all polynucleotides referred to herein, including RNA and DNA.

[0172] The "variable region" of an antibody refers to the variable region of an antibody light chain or the variable region of an antibody heavy chain, either alone or in combination. The heavy and light chain variable regions each consist of four framework regions (FRs) linked by three complementarity determining regions (CDRs), also known as hypervariable regions. The CDRs of each chain are held together in close proximity by the FRs and, together with the CDRs of 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) an approach based on interspecies sequence variability (i.e., Kabatetal. Sequences of Proteins of Immunological Interest, (5th ed., 1991, National Institutes of Health, Bethesda MD)); and (2) an approach 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 approach or a combination of both approaches.

[0173] A "constant region" of an antibody refers to the constant region of the antibody light chain or the constant region of the antibody heavy chain, either alone or in combination.

[0174] A "host cell" includes an individual cell or cell culture that can be or has been the recipient of a vector containing an exogenous polynucleotide. A host cell includes the 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. A host cell includes cells transfected in vivo with a polynucleotide of the disclosure.

[0175] 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 vary, the human IgG heavy chain Fc region is usually defined to stretch from an amino acid residue at position Cys226, or from an amino acid residue at position Pro230, to the carboxyl-terminus thereof. The numbering of residues in the Fc region is that of the EU index as in Kabat. (Kabat et al., Sequences of Proteins of Immunological Interest, 5th Ed. Public Health Service, National Institutes of Health, Bethesda, Md., 1991.) The Fc region of an immunoglobulin generally comprises two constant domains, CH2 and CH3.

[0176] 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, down-regulation of cell surface receptors (e.g., B cell receptor, BCR), and the like. Such effector functions generally require an Fc region in combination with a binding domain (e.g., an antibody variable domain) and may be assessed using a variety of assays known in the art for assessing such antibody effector functions.

[0177] A "native sequence Fc region" comprises an amino acid sequence identical to the amino acid sequence of an Fc region found in nature. A "variant Fc region" comprises an amino acid sequence that differs from that of a native sequence Fc region by virtue of at least one amino acid modification, but still retains at least one effector function of the native sequence Fc region. Preferably, the variant Fc region has at least one amino acid substitution, e.g., about 1 to about 10 amino acid substitutions in the native sequence Fc region or the Fc region of the parent polypeptide, preferably about 1 to about 5 amino acid substitutions in the native sequence Fc region or the Fc region of the parent polypeptide. The variant Fc region herein preferably has at least 80% sequence identity with the native sequence Fc region and / or the Fc region of the parent polypeptide, 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 identities within said ranges.

[0178] An "individual" or "subject" is a mammal, more preferably a human. Mammals also include, but are not limited to, farm animals, sport animals, pets, primates, horses, dogs, cats, mice and rats.

[0179] As used herein, "vector" refers to a construct that can deliver and preferably express 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 producer cells.

[0180] The term "effective amount" or "therapeutically effective amount" refers to an amount of an agent sufficient to produce a beneficial or desired result. The therapeutically effective amount may vary depending on one or more of the subject and disease state being treated, the weight and age of the subject, the severity of the disease state, the mode of administration, etc., which can be readily determined by one of ordinary skill in the art. The term "effective amount" also applies to a dose that provides an image for detection by an appropriate imaging method. The specific dose may vary depending on one or more of the particular agent selected, the dosing regimen to be followed, whether it is administered in combination with other compounds, the timing of administration, the tissue to be imaged, and the physical delivery system in which it is carried. An effective amount of an active agent may be administered in a single dose or multiple doses. The therapeutically effective amount of an antibody ranges from about 0.001 to about 25 mg / kg body weight, preferably from about 0.01 to about 25 mg / kg body weight, from about 0.1 to about 20 mg / kg body weight, or from about 1 to about 10 mg / kg body weight. Dosages may be adjusted as necessary to suit the observed effects of treatment and / or to be most effective in providing a cure, prevention, control of symptoms, etc., as determined by one of skill in the art. Appropriate doses are selected based on clinical indications by the treating physician or by the artisan. Ingredients may be described herein as having at least an effective amount, or at least an effective amount, to produce a desired result, such as any of those described herein, associated with a particular goal or objective. A desired therapeutic result herein may include, but is not limited to, treating, alleviating, or curing any symptoms from a disorder, cancer, immune-related disease, CD200R-associated disorder, and / or immune-related pathology, etc., as described herein and / or in the appended claims.

[0181] As used herein, "pharmaceutical acceptable carrier" or "pharmaceutical acceptable excipient" includes any material that, when combined with an active ingredient, allows the ingredient to retain biological activity and is non-reactive with the subject's immune system. Examples include, but are not limited to, any of the standard pharmaceutical carriers, such as phosphate buffered saline, water, emulsions such as oil / water emulsions, and various types of wetting agents. A preferred diluent for aerosol or parenteral administration is phosphate buffered saline or normal (0.9%) saline. Compositions containing such carriers are formulated by well-known conventional methods (see, for example, Remington's Pharmaceutical Sciences, 18th edition, A. Gennaro, ed., Mack Publishing Co., Easton, PA, 1990, and Remington, The Science and Practice of Pharmacy 20th Ed. Mack Publishing, 2000).

[0182] Throughout this specification and the appended claims, the methods and systems of the present disclosure as described herein may use conventional techniques and explanations of molecular biology (including recombinant techniques), cell biology, biochemistry, microarray and sequencing techniques that are within the skill of the art, unless otherwise indicated. Such conventional techniques include polymer array synthesis, hybridization and ligation of oligonucleotides, sequencing of oligonucleotides, and detection of hybridization using labels. Specific illustrations of suitable techniques can be obtained by reference to the examples herein. However, equivalent conventional procedures can of course also be used.Such prior art techniques and descriptions can be found in Green, et al., Eds., Genome Analysis: A Laboratory Manual Series (Vols. 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 Ed.) WH Freeman, NY (1995); Gait, “Oligonucleotide Synthesis: A Practical Approach” IRL Press, London (1984); Nelson and Cox, Lehninger, Principles of Biochemistry, 6. th Ed.,WHFreeman Pub.,New York(2012);RIFreshney,Culture of Animal Cells:A Manual of Basic Technique and Specialized Applications,6 th Ed., Wiley-Blackwell (2010); and Berg et al., Biochemistry, 5 thThe above-mentioned methods and methods can be found in standard laboratory manuals such as Ed., WH Freeman Pub., New York (2002), all of which are incorporated herein by reference in their entirety for all purposes. Before the compositions, research tools, and systems and methods of the present invention are described, it should be understood that the present disclosure is not limited to the specific systems and methods, compositions, targets, and uses described, which can of course vary. It should also be understood that the terms used herein are for the purpose of describing specific embodiments only, and are not intended to limit the scope of the present disclosure, which is limited only by the appended claims.

[0183] As used herein, the term "anti-CD200R antibody" or molecule refers to both antibodies and binding fragments thereof capable of binding to CD200R.

[0184] In the present disclosure, "antibody" refers to an immunoglobulin molecule that can specifically bind to a target, such as a carbohydrate, polynucleotide, lipid, or polypeptide, 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 that may or may not be functional. As used in the present disclosure, the term encompasses intact polyclonal or monoclonal antibodies, as well as fragments thereof (e.g., Fab, Fab', F(ab')2, diabody), Fv fragments, and single chain (ScFv) variants that contain an antigen recognition or binding site and have the ability to bind to an antigen. Antigen-binding antibodies or immunoglobulin fragments are well known in the art, and such fragments may have a functional or non-functional Fc receptor binding site. Furthermore, as used herein, the term is not limited to intact polyclonal or monoclonal antibodies, multispecific antibodies such as bispecific or multispecific antibodies generated from at least two intact antibodies, chimeric antibodies, humanized antibodies, single chain, chimeric, synthetic, recombinant, hybrid, mutated, grafted antibodies, human antibodies, and any other modified immunoglobulin molecule that contains an antigen binding site, so long as the antibody exhibits the desired biological activity.

[0185] There are five major classes of immunoglobulins: IgA, IgD, IgE, IgG, and IgM, some of which can be further divided into subclasses (isotypes), e.g., IgG1, IgG2, IgG3, IgG4, IgA1, and IgA2. The heavy chain constant domains corresponding to the different classes of immunoglobulins are called alpha, delta, epsilon, gamma, and mu, respectively. The subunit structures and three-dimensional configurations of the different classes of immunoglobulins are well known. Unless otherwise indicated by contextual constraints, the antibodies of the present disclosure may be derived from one of these classes or subclasses of antibodies. The heavy chain constant domains corresponding to the different classes of antibodies are typically designated by the corresponding lowercase Greek letters α, δ, ε, γ, and μ, respectively. The light chains of antibodies from any vertebrate species can be assigned to one of two clearly distinct types, called kappa (κ) and lambda (λ), based on the amino acid sequences of their constant domains.

[0186] Throughout this 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 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).

[0187] As used herein, a "monoclonal antibody" refers to an antibody obtained from a population of substantially homogeneous antibodies. Generally, the individual antibodies comprising the population are identical except for possible minor naturally occurring mutations. Monoclonal antibodies are highly specific, being directed against a single antigenic site. Furthermore, in contrast to polyclonal antibody preparations, which typically include different antibodies directed against different determinants (epitopes), each monoclonal antibody is directed against a single determinant on the antigen. The modifier "monoclonal" indicates the character of the antibody as being obtained from a substantially homogeneous antibody population and is not to be construed as requiring production of the antibody by any particular method. For example, monoclonal antibodies used in accordance with the present disclosure may be produced by the hybridoma method first described by Kohler and Milstein, 1975, Nature, 256:495, or may be produced by recombinant DNA as described in U.S. Pat. No. 4,816,567. The monoclonal antibodies can also be isolated from phage libraries generated using the techniques described in McCafferty et al., 1990, Nature 348:552-554, for example.

[0188] Whenever used herein, "human antibody" means an antibody having an amino acid sequence that corresponds to that of an antibody produced by a human and / or that has been made using any of the techniques for making human antibodies known in the art or of the present disclosure. This definition of a human antibody includes antibodies that comprise at least one human heavy chain polypeptide or at least one human light chain polypeptide. One such example is an antibody that comprises a mouse light chain and a human heavy chain polypeptide. Human antibodies can be produced using a variety of techniques known in the art. In some cases, human antibodies are selected from phage libraries that express 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 made by introducing human immunoglobulin loci into transgenic animals, e.g., mice in which the endogenous immunoglobulin genes have been partially or completely inactivated. This approach is described in U.S. Patent 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 directed against a target antigen (such B lymphocytes can be harvested from an individual or immunized in vitro). See, for example, 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.

[0189] 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 (e.g., Fv, Fab, Fab', F(ab')2, or other antigen-binding subsequences of antibodies) that contain minimal sequence derived from non-human immunoglobulin. In most cases, humanized antibodies are human immunoglobulins (recipient antibody) in which residues from a complementarity determining region (CDR) of the recipient are replaced by residues from a CDR of a non-human species (donor antibody) such as mouse, rat, or rabbit having the desired specificity, affinity, and capacity. In some instances, Fv framework region (FR) residues of the human immunoglobulin are replaced by corresponding non-human residues. Furthermore, humanized antibodies may comprise residues that are found neither in the recipient antibody, nor in the imported CDR or framework sequences, but are included to further refine and optimize antibody performance. Generally, a humanized antibody comprises substantially all of at least one, typically two, variable domains, with all or substantially all of the CDR regions corresponding to those of a non-human immunoglobulin and all or substantially all of the FR regions being those of a human immunoglobulin consensus sequence. The humanized antibody also optimally comprises at least a portion of an immunoglobulin constant region or domain (Fc), typically that 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 CDRs (1, 2, 3, 4, 5, 6) that are altered with respect to the original antibody, also referred to as one or more CDRs "derived from" one or more CDRs from the original antibody.

[0190] As used herein, the term "chimeric antibody" can refer to an antibody in which the variable region sequences are derived from one species and the constant region sequences are derived from another species, such as an antibody in which the variable region sequences are derived from a murine antibody and the constant region sequences are derived from a human antibody. In some embodiments, the antibodies provided herein are monoclonal antibodies.

[0191] As used herein, "antibody-dependent cellular cytotoxicity" and "ADCC" refer to a cell-mediated reaction in which non-specific cytotoxic cells expressing Fc receptors (FcR) (e.g., natural killer (NK) cells, neutrophils, and macrophages) recognize bound antibody on a target cell and subsequently cause lysis of the target cell. ADCC activity of a molecule of interest can be assessed using an in vitro ADCC assay, such as that described in U.S. Pat. No. 5,500,362 or U.S. Pat. No. 5,821,337. Effector cells useful for such assays include peripheral blood mononuclear cells (PBMC) and NK cells. Alternatively, or additionally, ADCC activity of a molecule of interest can be assessed in vivo, e.g., in an animal model such as that disclosed in Clynes et al., 1998, PNAS (USA), 95:652-656.

[0192] "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 can be performed, e.g., as described in Gazzano-Santoro et al., J. Immunol. Methods 202:163 (1996).

[0193] The term "specifically binds" to an epitope is well understood in the art, and methods for determining such specific binding are also well known in the art. A molecule is said to exhibit "specific binding" if it reacts or associates more frequently, more rapidly, with a longer duration, and / or with greater affinity with a particular cell, protein, or substance than with alternative cells, proteins, or substances. An antibody "specifically binds" or "preferentially binds" to a target if it binds with higher affinity, avidity, more readily, and / or for a longer duration than it binds to other substances. For example, an antibody that specifically or preferentially binds to CD200R is an antibody that binds to this epitope with higher 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. Thus, "specific binding" or "preferential binding" does not necessarily require (but can include) exclusive binding. Generally, but not necessarily, reference to binding implies preferential binding.

[0194] A "fragment," as applied to a protein, is a truncated form of a native biologically active protein that may or may not retain at least a portion of its therapeutic and / or biological activity. As used herein, the terms "antibody fragment molecule of the disclosure," "antibody fragment," and "antigen-binding fragment thereof" are used interchangeably herein.

[0195] Sequence identity

[0196] Sequence identity with respect to an anti-CD200R antibody sequence or any other amino acid sequence identified herein is defined as the percentage of amino acid residues in a query sequence that are identical to the amino acid residues of a second reference polypeptide sequence or portion thereof, after aligning the sequences and introducing gaps, if necessary, to achieve the maximum sequence identity percentage, without considering any conservative substitutions as part of the sequence identity. Alignment for purposes of determining percent amino acid sequence identity can be achieved in a variety of ways that are within the skill of the art, for example, using publicly available computer software such as BLAST, BLAST-2, ALIGN, or Megalign (DNASTAR) software. Those skilled in the art can determine appropriate parameters for measuring alignment, including any algorithms necessary to achieve maximum alignment over the full length of the sequences being compared. Percent identity can be measured over the entire length of the defined polypeptide sequence, or over a shorter length, for example, over the length of a fragment obtained from the 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. It is understood that such lengths are merely exemplary and any fragment length supported by the sequences shown herein in tables, figures or sequence listings may be used to describe the length for which percent identity can be measured. In some embodiments, percent identity is determined with respect to the full length of the reference sequence referred to, such as the sequences provided herein. For example, sequence comparison between two amino acid sequences (or shorter lengths thereof) of the present disclosure may be performed by the computer program Blastp (protein-protein BLAST), provided online by the Nation Center for Biotechnology Information (NCBI).The percentage amino acid sequence identity of a given amino acid sequence A to a given amino acid sequence B (which can alternatively be stated as a given amino acid sequence A having a certain % amino acid sequence identity to a given amino acid sequence B) is calculated by the following formula:

number

[0197] CD200 and CD200R

[0198] In some aspects, provided herein are compositions and methods relating to antibodies or antigen-binding fragments thereof that bind to 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 an important role in limiting immune cell proliferation, immune responses, and inflammation.

[0199] Without wishing to be bound by a particular theory, activation of the CD200R signaling pathway may result in inhibition of immune cell activation and proliferation. Antibodies that enhance CD200R signaling have the potential to down-regulate 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 1a glycoprotein that can be highly expressed in various cell types, such as dendritic cells, macrophages, B lymphocytes, neural cells, and endothelial cells, as well as some T lymphocytes. CD200 is involved in inhibitory signaling that inhibits or reduces the expression of genes involved in inflammatory responses. CD200 may function in concert with its natural receptor CD200R to activate immune suppressive signaling cascades.

[0200] Without wishing to be bound by any particular theory, in some cases, CD200R does not contain immunoreceptor tyrosine-based inhibitory motifs (ITIMs), which are typically present in many inhibitory receptors and can mediate their inhibitory role via recruitment of protein tyrosine phosphatases such as Src homology 2 domain-containing phosphatase (SHP)1, SH2, or inositol phosphatase (SHIP) upon phosphorylation. Instead, in some cases, the molecular signaling mechanism of CD200R following activation involves direct interaction of adaptor proteins downstream of tyrosine kinase (Dok2) with CD200R membrane-distal tyrosine residues located within a phosphotyrosine-binding (PTB) domain recognition motif (NPxY). This interaction can result in the binding and recruitment of the SH2 domain-containing protein, p21 activator of RAS (RasGAP). Formation of the Dok2-RasGAP complex can inhibit Ras activation and other downstream inflammatory signals through inhibition of key 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, initiating a signaling cascade that recruits SHIP and RasGAP. Dok2 can be regulated by Dok1 through Crk Like (CrkL)-RasGAP repression, and both Dok2 and Dok1 can be recruited during CD200-CD200R interaction, leading to the recruitment of RasGAP and SH2-containing inositol phosphatases.In some cases, Dok1 activation is initiated via binding to one of three phosphotyrosine residues located on the cytoplasmic amino acid chain of CD200R. This Dok1-phosphotyrosine binding can then suppress the effect of Dok2 on Ras via activation of CrkL.

[0201] In some aspects, provided herein are antibodies, compositions, nucleic acids, vectors, host cells, kits, uses thereof, and methods of making thereof that can avoid 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. Antibody sequence

[0202] In this disclosure, compositions, therapeutic agents, kits, vectors, nucleic acid sequences, manufacturing, culture, and / or methods are provided herein for producing CD200R agonist antibodies, or antigen-binding or functional fragments thereof, that enhance the biological effects of CD200R activation, e.g., inhibiting the activity or proliferation of immune cells expressing the CD200R molecule to which the antibody binds, or promoting inflammatory responses and downregulation of CD200R-expressing immune cell responses. In some cases, CD200R agonist antibodies enhance downstream signaling of CD200R triggered by CD200 binding. In some cases, CD200R agonist antibodies enhance the interaction between CD200 and CD200R. In some cases, CD200R agonist antibodies enhance downstream signaling of CD200R without increasing or enhancing the interaction between CD200 and CD200R. In some cases, a CD200R agonistic antibody activates or enhances CD200R signaling in the absence of CD200 binding to CD200R.

[0203] In some embodiments, the antibodies or antigen-binding fragments (e.g., isolated antibodies) provided herein specifically bind to CD200R and enhance the CD200R signaling pathway in cells having CD200R expressed on their surface.

[0204] In some embodiments, the antibodies or antigen-binding fragments (e.g., isolated antibodies) provided herein are CD200R antibodies that comprise a heavy chain. In some embodiments, the antibodies or antigen-binding fragments provided herein are CD200R antibodies that comprise a light chain. In some embodiments, the antibodies or antigen-binding fragments provided herein are CD200R antibodies that comprise an Fc region.

[0205] 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 set forth in any 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 0-3 amino acid modifications. In some embodiments, the heavy chain CDR comprises a sequence set forth in any 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 0-2 amino acid modifications. In some embodiments, the heavy chain CDRs comprise a sequence set forth in any 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 0-1 amino acid modifications.

[0206] In some embodiments, the heavy chain comprises a heavy chain variable region. In some cases, the heavy chain variable region comprises a heavy chain complementarity determining region 1 (CDRH1), CDRH2, and CDRH3. In some cases, CDRH1, CDRH2, and CDRH3 comprise the sequences set forth in SEQ ID NOs: 3, 41, and 70, respectively, each with 0-3 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 0-3 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 0-3 amino acid modifications, such as 0, 1, 2, or 3 modifications. In some cases, CDRH1, CDRH2, and CDRH3 comprise sequences set forth in SEQ ID NOs: 3, 41, and 5, respectively, with 0-3 amino acid modifications, such as 0, 1, 2, or 3 modifications each. In some cases, CDRH1, CDRH2, and CDRH3 comprise sequences set forth in SEQ ID NOs: 11, 12, and 13, respectively, with 0-3 amino acid modifications, such as 0, 1, 2, or 3 modifications each. In some cases, CDRH1, CDRH2, and CDRH3 comprise sequences set forth in SEQ ID NOs: 19, 20, and 21, respectively, with 0-3 amino acid modifications, such as 0, 1, 2, or 3 modifications each. In some cases, CDRH1, CDRH2, and CDRH3 comprise sequences set forth in SEQ ID NOs: 27, 28, and 29, respectively, with 0-3 amino acid modifications, such as 0, 1, 2, or 3 modifications each. In some cases, CDRH1, CDRH2, and CDRH3 comprise the sequences set forth in SEQ ID NOs: 35, 36, and 37, respectively, with 0-3 amino acid modifications, such as 0, 1, 2, or 3 modifications each.

[0207] In some embodiments, the light chain further comprises at least one light chain complementarity determining region (CDR). In some embodiments, the light chain CDR comprises a sequence set forth in any of SEQ ID NOs: 6, 7, 8, 14, 15, 16, 22, 23, 24, 30, 31, 32, 38, 39, 40, 67, 68, or 87-91 with 0-3 amino acid modifications. In some embodiments, the light chain CDR comprises a sequence set forth in any of SEQ ID NOs: 6, 7, 8, 14, 15, 16, 22, 23, 24, 30, 31, 32, 38, 39, 40, 67, 68, or 87-91 with 0-2 amino acid modifications. In some embodiments, the light chain CDR comprises a sequence set forth in any of SEQ ID NOs: 6, 7, 8, 14, 15, 16, 22, 23, 24, 30, 31, 32, 38, 39, 40, 67, 68, or 87-91 with 0-1 amino acid modifications.

[0208] In some embodiments, the heavy chain comprises a light chain variable region. In some cases, the light chain variable region comprises a light chain complementarity determining region 1 (CDRL1), CDRL2, and CDRL3. In some cases, CDRL1, CDRL2, and CDRL3 comprise the sequences set forth in SEQ ID NOs: 6, 7, and 8, respectively, with 0-3 amino acid modifications, such as 0, 1, 2, or 3 modifications each. In some cases, CDRL1, CDRL2, and CDRL3 comprise the sequences set forth in SEQ ID NOs: 6, 67, and 8, respectively, with 0-3 amino acid modifications, such as 0, 1, 2, or 3 modifications each. In some cases, CDRL1, CDRL2, and CDRL3 comprise the sequences set forth in SEQ ID NOs: 6, 68, and 8, respectively, with 0-3 amino acid modifications, such as 0, 1, 2, or 3 modifications each. In some cases, CDRL1, CDRL2, and CDRL3 comprise sequences set forth in SEQ ID NOs: 14, 15, and 16, respectively, with 0-3 amino acid modifications, such as 0, 1, 2, or 3 modifications each. In some cases, CDRL1, CDRL2, and CDRL3 comprise sequences set forth in SEQ ID NOs: 22, 23, and 24, respectively, with 0-3 amino acid modifications, such as 0, 1, 2, or 3 modifications each. In some cases, CDRL1, CDRL2, and CDRL3 comprise sequences set forth in SEQ ID NOs: 30, 31, and 32, respectively, with 0-3 amino acid modifications, such as 0, 1, 2, or 3 modifications each. In some cases, CDRL1, CDRL2, and CDRL3 comprise sequences set forth in SEQ ID NOs: 38, 39, and 40, respectively, with 0-3 amino acid modifications, such as 0, 1, 2, or 3 modifications each. In some cases, CDRL1, CDRL2, and CDRL3 comprise the sequences set forth in SEQ ID NOs: 6, 7, and 8, respectively, each with 0-2 amino acid modifications. In some cases, CDRL1, CDRL2, and CDRL3 comprise the sequences set forth in SEQ ID NOs: 6, 67, and 8, respectively, each with 0-2 amino acid modifications. In some cases, CDRL1, CDRL2, and CDRL3 comprise the sequences set forth in SEQ ID NOs: 6, 68, and 8, respectively, each with 0-2 amino acid modifications.In some cases, CDRL1, CDRL2, and CDRL3 comprise sequences set forth in SEQ ID NOs: 14, 15, and 16, respectively, each with 0-2 amino acid modifications. In some cases, CDRL1, CDRL2, and CDRL3 comprise sequences set forth in SEQ ID NOs: 22, 23, and 24, respectively, each with 0-2 amino acid modifications. In some cases, CDRL1, CDRL2, and CDRL3 comprise sequences set forth in SEQ ID NOs: 30, 31, and 32, respectively, each with 0-2 amino acid modifications. In some cases, CDRL1, CDRL2, and CDRL3 comprise sequences set forth in SEQ ID NOs: 38, 39, and 40, respectively, each with 0-2 amino acid modifications. In some cases, CDRL1, CDRL2, and CDRL3 comprise sequences set forth in SEQ ID NOs: 14, 15, and 16, respectively, each with 0-2 amino acid modifications. In some cases, CDRL1, CDRL2, and CDRL3 comprise the sequences set forth in SEQ ID NOs: 22, 23, and 24, respectively, each with 0-1 amino acid modifications. In some cases, CDRL1, CDRL2, and CDRL3 comprise the sequences set forth in SEQ ID NOs: 30, 31, and 32, respectively, each with 0-1 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 with 0-1 amino acid modifications.

[0209] In some embodiments, an antibody (or antigen-binding fragment, hereinafter referred to as "antibody" to refer to a full-length antibody or antigen-binding fragment of an antibody provided herein) provided herein comprises a heavy chain comprising at least one heavy chain CDR set forth in any of SEQ ID NO: 3, 4, 41, 5, 69, or 70, with 0-3 amino acid modifications, and a light chain comprising at least one light chain CDR set forth in any of SEQ ID NO: 6, 7, or 8, with 0-3 amino acid modifications. In some cases, an antibody provided herein comprises a heavy chain comprising at least one heavy chain CDR set forth in any of SEQ ID NO: 3, 4, 41, 5, 69, or 70, with 0-3 amino acid modifications, and a light chain comprising at least one light chain CDR set forth in any of SEQ ID NO: 6, 67, or 8, with 0-3 amino acid modifications. In some cases, an antibody provided herein comprises a heavy chain comprising at least one heavy chain CDR set forth in any of SEQ ID NOs: 3, 4, 41, 5, 69, or 70 with 0-3 amino acid modifications, and a light chain comprising at least one light chain CDR set forth in any of SEQ ID NOs: 6, 68, or 8 with 0-3 amino acid modifications. In some cases, an antibody provided herein comprises a heavy chain comprising at least one heavy chain CDR set forth in any of SEQ ID NOs: 3, 41, or 70 with 0-3 amino acid modifications, and a light chain comprising at least one light chain CDR set forth in any of SEQ ID NOs: 6, 67, or 8 with 0-3 amino acid modifications. In some cases, an antibody provided herein comprises a heavy chain comprising at least one heavy chain CDR set forth in any of SEQ ID NOs: 3, 41, or 69 with 0-3 amino acid modifications, and a light chain comprising at least one light chain CDR set forth in any of SEQ ID NOs: 6, 67, or 8 with 0-3 amino acid modifications. In some cases, an antibody provided herein comprises a heavy chain comprising at least one heavy chain CDR set forth in any of SEQ ID NOs: 11, 12, or 13 with 0-3 amino acid modifications, and a light chain comprising at least one light chain CDR set forth in any of SEQ ID NOs: 14, 15, or 16 with 0-3 amino acid modifications.In some cases, the antibodies provided herein comprise a heavy chain comprising at least one heavy chain CDR set forth in any of SEQ ID NOs: 19, 20, or 21 with 0-3 amino acid modifications, and a light chain comprising at least one light chain CDR set forth in any of SEQ ID NOs: 22, 23, or 24 with 0-3 amino acid modifications. In some cases, the antibodies provided herein comprise a heavy chain comprising at least one heavy chain CDR set forth in any of SEQ ID NOs: 27, 28, or 29 with 0-3 amino acid modifications, and a light chain comprising at least one light chain CDR set forth in any of SEQ ID NOs: 30, 31, or 32 with 0-3 amino acid modifications. In some cases, the antibodies provided herein comprise a heavy chain comprising at least one heavy chain CDR set forth in any of SEQ ID NOs: 35, 36, or 37 with 0-3 amino acid modifications, and a light chain comprising at least one light chain CDR set forth in any of SEQ ID NOs: 38, 39, or 40 with 0-3 amino acid modifications.

[0210] In some cases, an antibody provided herein comprises a heavy chain comprising at least one heavy chain CDR set forth in any of SEQ ID NO: 3, 4, 41, 5, 69, or 70 with 0-2 amino acid modifications, and a light chain comprising at least one light chain CDR set forth in any of SEQ ID NO: 6, 7, or 8 with 0-2 amino acid modifications. In some cases, an antibody provided herein comprises a heavy chain comprising at least one heavy chain CDR set forth in any of SEQ ID NO: 3, 4, 41, 5, 69, or 70 with 0-2 amino acid modifications, and a light chain comprising at least one light chain CDR set forth in any of SEQ ID NO: 6, 67, or 8 with 0-2 amino acid modifications. In some cases, an antibody provided herein comprises a heavy chain comprising at least one heavy chain CDR set forth in any of SEQ ID NOs: 3, 4, 41, 5, 69, or 70 with 0-2 amino acid modifications, and a light chain comprising at least one light chain CDR set forth in any of SEQ ID NOs: 6, 68, or 8 with 0-2 amino acid modifications. In some cases, an antibody provided herein comprises a heavy chain comprising at least one heavy chain CDR set forth in any of SEQ ID NOs: 11, 12, or 13 with 0-2 amino acid modifications, and a light chain comprising at least one light chain CDR set forth in any of SEQ ID NOs: 14, 15, or 16 with 0-2 amino acid modifications. In some cases, an antibody provided herein comprises a heavy chain comprising at least one heavy chain CDR set forth in any of SEQ ID NOs: 19, 20, or 21 with 0-2 amino acid modifications, and a light chain comprising at least one light chain CDR set forth in any of SEQ ID NOs: 22, 23, or 24 with 0-2 amino acid modifications. In some cases, an antibody provided herein comprises a heavy chain comprising at least one heavy chain CDR set forth in any of SEQ ID NOs: 27, 28, or 29 with 0-2 amino acid modifications, and a light chain comprising at least one light chain CDR set forth in any of SEQ ID NOs: 30, 31, or 32 with 0-2 amino acid modifications.In some cases, an antibody provided herein comprises a heavy chain comprising at least one heavy chain CDR set forth in any of SEQ ID NOs: 35, 36, or 37 with 0-2 amino acid modifications, and a light chain comprising at least one light chain CDR set forth in any of SEQ ID NOs: 38, 39, or 40 with 0-2 amino acid modifications.

[0211] In some cases, an antibody provided herein comprises a heavy chain comprising at least one heavy chain CDR set forth in any of SEQ ID NOs: 3, 4, 41, 5, 69, or 70 with 0-2 amino acid modifications, and a light chain comprising at least one light chain CDR set forth in any of SEQ ID NOs: 6, 7, or 8 with 0-1 amino acid modifications. In some cases, an antibody provided herein comprises a heavy chain comprising at least one heavy chain CDR set forth in any of SEQ ID NOs: 3, 4, 41, 5, 69, or 70 with 0-2 amino acid modifications, and a light chain comprising at least one light chain CDR set forth in any of SEQ ID NOs: 6, 67, or 8 with 0-1 amino acid modifications. In some cases, an antibody provided herein comprises a heavy chain comprising at least one heavy chain CDR set forth in any of SEQ ID NOs: 3, 4, 41, 5, 69, or 70 with 0-2 amino acid modifications, and a light chain comprising at least one light chain CDR set forth in any of SEQ ID NOs: 6, 68, or 8 with 0-1 amino acid modifications. In some cases, an antibody provided herein comprises a heavy chain comprising at least one heavy chain CDR set forth in any of SEQ ID NOs: 11, 12, or 13 with 0-1 amino acid modifications, and a light chain comprising at least one light chain CDR set forth in any of SEQ ID NOs: 14, 15, or 16 with 0-1 amino acid modifications. In some cases, an antibody provided herein comprises a heavy chain comprising at least one heavy chain CDR set forth in any of SEQ ID NOs: 19, 20, or 21 with 0-1 amino acid modifications, and a light chain comprising at least one light chain CDR set forth in any of SEQ ID NOs: 22, 23, or 24 with 0-1 amino acid modifications. In some cases, an antibody provided herein comprises a heavy chain comprising at least one heavy chain CDR set forth in any of SEQ ID NOs: 27, 28, or 29 with 0-1 amino acid modifications, and a light chain comprising at least one light chain CDR set forth in any of SEQ ID NOs: 30, 31, or 32 with 0-1 amino acid modifications.In some cases, an antibody provided herein comprises a heavy chain comprising at least one heavy chain CDR set forth in any of SEQ ID NOs: 35, 36, or 37 with 0-1 amino acid modifications, and a light chain comprising at least one light chain CDR set forth in any of SEQ ID NOs: 38, 39, or 40 with 0-1 amino acid modifications.

[0212] In some embodiments, the antibodies provided herein comprise a heavy chain comprising a heavy chain variable region further comprising heavy chain complementarity determining region 1 (CDRH1), CDRH2, and CDRH3, and a light chain comprising a light chain variable region comprising light chain complementarity determining region 1 (CDRL1), CDRL2, and CDRL3, the light chain variable region comprising CDRL1, CDRL2, and CDRL3. In some cases, CDRH1, CDRH2, and CDRH3 comprise the sequences set forth in SEQ ID NOs: 3, 4, and 5, respectively, with 0-3 amino acid modifications, such as 0, 1, 2, or 3 modifications each, and CDRL1, CDRL2, and CDRL3 comprise the sequences set forth in SEQ ID NOs: 6, 7, and 8, respectively, with 0-3 amino acid modifications, such as 0, 1, 2, or 3 modifications each. In some cases, CDRH1, CDRH2, and CDRH3 comprise the sequences set forth in SEQ ID NOs: 3, 4, and 5, respectively, with 0-3 amino acid modifications, such as 0, 1, 2, or 3 modifications each, and CDRL1, CDRL2, and CDRL3 comprise the sequences set forth in SEQ ID NOs: 6, 67, and 8, respectively, with 0-3 amino acid modifications, such as 0, 1, 2, or 3 modifications each. In some cases, CDRH1, CDRH2, and CDRH3 comprise the sequences set forth in SEQ ID NOs: 3, 41, and 69, respectively, with 0-3 amino acid modifications, such as 0, 1, 2, or 3 modifications each, and CDRL1, CDRL2, and CDRL3 comprise the sequences set forth in SEQ ID NOs: 6, 67, and 8, respectively, with 0-3 amino acid modifications, such as 0, 1, 2, or 3 modifications each. In some cases, CDRH1, CDRH2, and CDRH3 comprise the sequences set forth in SEQ ID NOs: 3, 41, 70, respectively, with 0-3 amino acid modifications, such as 0, 1, 2, or 3 modifications each, and CDRL1, CDRL2, and CDRL3 comprise the sequences set forth in SEQ ID NOs: 6, 67, and 8, respectively, with 0-3 amino acid modifications, such as 0, 1, 2, or 3 modifications each.In some cases, CDRH1, CDRH2, and CDRH3 comprise the sequences set forth in SEQ ID NOs: 3, 4, and 5, respectively, with 0-3 amino acid modifications, such as 0, 1, 2, or 3 modifications each, and CDRL1, CDRL2, and CDRL3 comprise the sequences set forth in SEQ ID NOs: 6, 68, and 8, respectively, with 0-3 amino acid modifications, such as 0, 1, 2, or 3 modifications each. In some cases, CDRH1, CDRH2, and CDRH3 comprise the sequences set forth in SEQ ID NOs: 3, 41, and 5, respectively, with 0-3 amino acid modifications, such as 0, 1, 2, or 3 modifications each, and CDRL1, CDRL2, and CDRL3 comprise the sequences set forth in SEQ ID NOs: 6, 7, and 8, respectively, with 0-3 amino acid modifications, such as 0, 1, 2, or 3 modifications each. In some cases, CDRH1, CDRH2, and CDRH3 comprise the sequences set forth in SEQ ID NOs: 3, 41, and 5, respectively, with 0-3 amino acid modifications, such as 0, 1, 2, or 3 modifications each, and CDRL1, CDRL2, and CDRL3 comprise the sequences set forth in SEQ ID NOs: 6, 67, and 8, respectively, with 0-3 amino acid modifications, such as 0, 1, 2, or 3 modifications each. In some cases, CDRH1, CDRH2, and CDRH3 comprise the sequences set forth in SEQ ID NOs: 3, 41, and 5, respectively, with 0-3 amino acid modifications, such as 0, 1, 2, or 3 modifications each, and CDRL1, CDRL2, and CDRL3 comprise the sequences set forth in SEQ ID NOs: 6, 68, and 8, respectively, with 0-3 amino acid modifications, such as 0, 1, 2, or 3 modifications each. In some cases, CDRH1, CDRH2, and CDRH3 comprise the sequences set forth in SEQ ID NOs: 11, 12, and 13, respectively, with 0-3 amino acid modifications, such as 0, 1, 2, or 3 modifications each, and CDRL1, CDRL2, and CDRL3 comprise the sequences set forth in SEQ ID NOs: 14, 15, and 16, respectively, with 0-3 amino acid modifications, such as 0, 1, 2, or 3 modifications each.In some cases, CDRH1, CDRH2, and CDRH3 comprise sequences set forth in SEQ ID NOs: 19, 20, and 21, respectively, with 0-3 amino acid modifications, such as 0, 1, 2, or 3 modifications each, and CDRL1, CDRL2, and CDRL3 comprise sequences set forth in SEQ ID NOs: 22, 23, and 24, respectively, with 0-3 amino acid modifications, such as 0, 1, 2, or 3 modifications each. In some cases, CDRH1, CDRH2, and CDRH3 comprise sequences set forth in SEQ ID NOs: 27, 28, and 29, respectively, with 0-3 amino acid modifications, such as 0, 1, 2, or 3 modifications each, and CDRL1, CDRL2, and CDRL3 comprise sequences set forth in SEQ ID NOs: 30, 31, and 32, respectively, with 0-3 amino acid modifications, such as 0, 1, 2, or 3 modifications each. In some cases, CDRH1, CDRH2, and CDRH3 comprise the sequences set forth in SEQ ID NOs: 35, 36, and 37, respectively, with 0-3 amino acid modifications, such as 0, 1, 2, or 3 modifications each, and CDRL1, CDRL2, and CDRL3 comprise the sequences set forth in SEQ ID NOs: 38, 39, and 40, respectively, with 0-3 amino acid modifications, such as 0, 1, 2, or 3 modifications each.

[0213] In some cases, CDRH1, CDRH2, and CDRH3 comprise sequences set forth in SEQ ID NOs: 3, 4, and 5, respectively, with 0-2 amino acid modifications, and CDRL1, CDRL2, and CDRL3 comprise sequences set forth in SEQ ID NOs: 6, 7, and 8, respectively, with 0-2 amino acid modifications. In some cases, CDRH1, CDRH2, and CDRH3 comprise sequences set forth in SEQ ID NOs: 3, 4, and 5, respectively, with 0-2 amino acid modifications, and CDRL1, CDRL2, and CDRL3 comprise sequences set forth in SEQ ID NOs: 6, 67, and 8, respectively, with 0-2 amino acid modifications. In some cases, CDRH1, CDRH2, and CDRH3 comprise sequences set forth in SEQ ID NOs: 3, 41, and 69, respectively, with 0-2 amino acid modifications, and CDRL1, CDRL2, and CDRL3 comprise sequences set forth in SEQ ID NOs: 6, 67, and 8, respectively, with 0-2 amino acid modifications. In some cases, CDRH1, CDRH2, and CDRH3 comprise sequences set forth in SEQ ID NOs: 3, 41, and 70, respectively, with 0-2 amino acid modifications, and CDRL1, CDRL2, and CDRL3 comprise sequences set forth in SEQ ID NOs: 6, 67, and 8, respectively, with 0-2 amino acid modifications. In some cases, CDRH1, CDRH2, and CDRH3 comprise sequences set forth in SEQ ID NOs: 3, 4, and 5, respectively, with 0-2 amino acid modifications, and CDRL1, CDRL2, and CDRL3 comprise sequences set forth in SEQ ID NOs: 6, 68, and 8, respectively, with 0-2 amino acid modifications. In some cases, CDRH1, CDRH2, and CDRH3 comprise sequences set forth in SEQ ID NOs: 3, 41, and 5, respectively, with 0-2 amino acid modifications, and CDRL1, CDRL2, and CDRL3 comprise sequences set forth in SEQ ID NOs: 6, 7, and 8, respectively, with 0-2 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 0-2 amino acid modifications, and CDRL1, CDRL2, and CDRL3 comprise the sequences set forth in SEQ ID NOs: 6, 67, and 8, respectively, each with 0-2 amino acid modifications.In some cases, CDRH1, CDRH2, and CDRH3 comprise sequences set forth in SEQ ID NOs: 3, 41, and 5, respectively, each with 0-2 amino acid modifications, and CDRL1, CDRL2, and CDRL3 comprise sequences set forth in SEQ ID NOs: 6, 68, and 8, respectively, each with 0-2 amino acid modifications. In some cases, CDRH1, CDRH2, and CDRH3 comprise sequences set forth in SEQ ID NOs: 11, 12, and 13, respectively, each with 0-2 amino acid modifications, and CDRL1, CDRL2, and CDRL3 comprise sequences set forth in SEQ ID NOs: 14, 15, and 16, respectively, each with 0-2 amino acid modifications. In some cases, CDRH1, CDRH2, and CDRH3 comprise sequences set forth in SEQ ID NOs: 19, 20, and 21, respectively, each with 0-2 amino acid modifications, and CDRL1, CDRL2, and CDRL3 comprise sequences set forth in SEQ ID NOs: 22, 23, and 24, respectively, each with 0-2 amino acid modifications. In some cases, CDRH1, CDRH2, and CDRH3 comprise sequences set forth in SEQ ID NOs: 27, 28, and 29, respectively, each with 0-2 amino acid modifications, and CDRL1, CDRL2, and CDRL3 comprise sequences set forth in SEQ ID NOs: 30, 31, and 32, respectively, each with 0-2 amino acid modifications. In some cases, CDRH1, CDRH2, and CDRH3 comprise sequences set forth in SEQ ID NOs: 35, 36, and 37, respectively, each with 0-2 amino acid modifications, and CDRL1, CDRL2, and CDRL3 comprise sequences set forth in SEQ ID NOs: 38, 39, and 40, respectively, each with 0-2 amino acid modifications.

[0214] In some cases, CDRH1, CDRH2, and CDRH3 comprise sequences set forth in SEQ ID NOs: 3, 4, and 5, respectively, with 0-1 amino acid modifications, and CDRL1, CDRL2, and CDRL3 comprise sequences set forth in SEQ ID NOs: 6, 7, and 8, respectively, with 0-1 amino acid modifications. In some cases, CDRH1, CDRH2, and CDRH3 comprise sequences set forth in SEQ ID NOs: 3, 4, and 5, respectively, with 0-1 amino acid modifications, and CDRL1, CDRL2, and CDRL3 comprise sequences set forth in SEQ ID NOs: 6, 67, and 8, respectively, with 0-1 amino acid modifications. In some cases, CDRH1, CDRH2, and CDRH3 comprise sequences set forth in SEQ ID NOs: 3, 41, and 69, respectively, with 0-1 amino acid modifications, and CDRL1, CDRL2, and CDRL3 comprise sequences set forth in SEQ ID NOs: 6, 67, and 8, respectively, with 0-1 amino acid modifications. In some cases, CDRH1, CDRH2, and CDRH3 comprise sequences set forth in SEQ ID NOs: 3, 41, and 70, respectively, with 0-1 amino acid modifications, and CDRL1, CDRL2, and CDRL3 comprise sequences set forth in SEQ ID NOs: 6, 67, and 8, respectively, with 0-1 amino acid modifications. In some cases, CDRH1, CDRH2, and CDRH3 comprise sequences set forth in SEQ ID NOs: 3, 4, and 5, respectively, with 0-1 amino acid modifications, and CDRL1, CDRL2, and CDRL3 comprise sequences set forth in SEQ ID NOs: 6, 68, and 8, respectively, with 0-1 amino acid modifications. In some cases, CDRH1, CDRH2, and CDRH3 comprise sequences set forth in SEQ ID NOs: 3, 41, and 5, respectively, with 0-1 amino acid modifications, and CDRL1, CDRL2, and CDRL3 comprise sequences set forth in SEQ ID NOs: 6, 7, and 8, respectively, with 0-1 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 with 0-1 amino acid modifications, and CDRL1, CDRL2, and CDRL3 comprise the sequences set forth in SEQ ID NOs: 6, 67, and 8, respectively, each with 0-1 amino acid modifications.In some cases, CDRH1, CDRH2, and CDRH3 comprise sequences set forth in SEQ ID NOs: 3, 41, and 5, respectively, each with 0-1 amino acid modifications, and CDRL1, CDRL2, and CDRL3 comprise sequences set forth in SEQ ID NOs: 6, 68, and 8, respectively, each with 0-1 amino acid modifications. In some cases, CDRH1, CDRH2, and CDRH3 comprise sequences set forth in SEQ ID NOs: 11, 12, and 13, respectively, each with 0-1 amino acid modifications, and CDRL1, CDRL2, and CDRL3 comprise sequences set forth in SEQ ID NOs: 14, 15, and 16, respectively, each with 0-1 amino acid modifications. In some cases, CDRH1, CDRH2, and CDRH3 comprise sequences set forth in SEQ ID NOs: 19, 20, and 21, respectively, each with 0-1 amino acid modifications, and CDRL1, CDRL2, and CDRL3 comprise sequences set forth in SEQ ID NOs: 22, 23, and 24, respectively, each with 0-1 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 0-1 amino acid modifications, and CDRL1, CDRL2, and CDRL3 comprise the sequences set forth in SEQ ID NOs: 30, 31, and 32, respectively, each with 0-1 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 with 0-1 amino acid modifications, and CDRL1, CDRL2, and CDRL3 comprise the sequences set forth in SEQ ID NOs: 38, 39, and 40, respectively, each with 0-1 amino acid modifications.

[0215] 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: 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 set forth in 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 set forth in 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 set forth in 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 set forth in 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 set forth in 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 set forth in SEQ ID NO: 1, 9, 17, 25, 33, 42, 43, 44, 45, 46, 47, 71, 72, or 93.

[0216] In some embodiments, the antibodies provided herein comprise a heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 1, 9, 17, 25, 33, 42, 43, 44, 45, 46, 47, 71, 72, or 93 with 0-3 amino acid modifications. In some embodiments, the antibodies provided herein comprise a heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 1, 9, 17, 25, 33, 42, 43, 44, 45, 46, 47, 71, 72, or 93 with 0-2 amino acid modifications. In some embodiments, the antibodies provided herein comprise a heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 1, 9, 17, 25, 33, 42, 43, 44, 45, 46, 47, 71, 72, or 93 with 0-2 amino acid modifications. In some embodiments, the antibodies provided herein comprise a heavy chain variable region comprising the amino acid sequence set forth 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 modifications. In some embodiments, the antibodies provided herein comprise a heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 1, 9, 17, 25, 33, 42, 43, 44, 45, 46, 47, 71, 72, or 93.

[0217] 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 set forth in 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 set forth in 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 set forth in 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 set forth in 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 set forth in 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 set forth in 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 set forth in SEQ ID NO: 2, 10, 18, 26, 34, 48, 49, 50, 51, 52, 65, 66, or 94.

[0218] In some embodiments, the antibodies provided herein comprise a light chain variable region comprising the amino acid sequence set forth 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 the amino acid sequence set forth 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 the amino acid sequence set forth in SEQ ID NO: 2, 10, 18, 26, 34, 48, 49, 50, 51, 52, 65, 66, or 94 with 0 to 1 amino acid modifications. In some embodiments, the antibodies provided herein comprise a light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 2, 10, 18, 26, 34, 48, 49, 50, 51, 52, 65, 66, or 94.

[0219] 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:1, 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: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 96% 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 96% 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 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 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.

[0220] 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 set forth 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 set forth in SEQ ID NO: 10.

[0221] 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, an antibody provided herein comprises 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.

[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 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, an antibody provided herein comprises 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:25, 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:26.

[0223] 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 set forth 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 set forth in SEQ ID NO: 34.

[0224] 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 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 the amino acid sequence set forth in 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 set forth 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 set forth in SEQ ID NOs: 2, 48, 49, 50, 51, 52, 65, 66, or 94. In some cases, an antibody provided herein comprises 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: 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 set forth in SEQ ID NOs: 2, 48, 49, 50, 51, 52, 65, 66, or 94. In some cases, an antibody provided herein comprises 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: 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 set forth in 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 set forth 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 set forth in 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 set forth 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 set forth in SEQ ID NOs: 2, 48, 49, 50, 51, 52, 65, 66, or 94. In some cases, an antibody provided herein comprises a heavy chain variable region comprising an amino acid sequence having 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 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, 48, 49, 50, 51, 52, 65, 66, or 94.

[0225] 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 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 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 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 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 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 98% sequence identity to the amino acid sequence set forth in SEQ ID NOs: 48, 49, 50, 51, 52, 65, 66, or 94.In some cases, an antibody provided herein comprises a heavy chain variable region comprising an amino acid sequence having at least 99% 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 100% sequence identity to the amino acid sequence set forth in SEQ ID NO: 48, 49, 50, 51, 52, 65, 66, or 94.

[0226] 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 a total of no more than 10, 9, 8, 7, 6, 5, 4, 3, 2, 1, or 0 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 a total of no more than 10, 9, 8, 7, 6, 5, 4, 3, 2, 1, or 0 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 a total of no more than 10 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 a total of no more than 10 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 a total of no more than 7 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 a total of no more than 7 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 a total of no more than 5 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 a total of no more than 5 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 a total of no more than three 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 a total of no more than three 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 a total of no more than two 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 a total of no more than two 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 a total of no more than one 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 a total of no more than one substitution, deletion, and / or insertion in the amino acid sequence set forth in SEQ ID NO: 2.

[0227] 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 a total of no more than 10, 9, 8, 7, 6, 5, 4, 3, 2, 1, or 0 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 a total of no more than 10, 9, 8, 7, 6, 5, 4, 3, 2, 1, or 0 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 a total of no more than 10 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 a total of no more than 10 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 a total of no more than 7 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 a total of no more than 7 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 a total of no more than 5 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 a total of no more than 5 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 a total of no more than three 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 a total of no more than three 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 a total of no more than two 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 a total of no more than two 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 a total of no more than one 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 a total of no more than one substitution, deletion, and / or insertion in the amino acid sequence set forth in SEQ ID NO: 48.

[0228] 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 no more than 10, 9, 8, 7, 6, 5, 4, 3, 2, 1, or 0 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 no more than 10, 9, 8, 7, 6, 5, 4, 3, 2, 1, or 0 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 a total of no more than 10 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 a total of no more than 10 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 a total of no more than 7 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 a total of no more than 7 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 a total of no more than 5 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 a total of no more than 5 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 a total of no more than three 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 a total of no more than three 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 a total of no more than two 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 a total of no more than two 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 a total of no more than one 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 a total of no more than one substitution, deletion, and / or insertion in the amino acid sequence set forth in SEQ ID NO: 49.

[0229] 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 a total of no more than 10, 9, 8, 7, 6, 5, 4, 3, 2, 1, or 0 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 a total of no more than 10, 9, 8, 7, 6, 5, 4, 3, 2, 1, or 0 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 a total of no more than 10 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 a total of no more than 10 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 a total of no more than 7 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 a total of no more than 7 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 a total of no more than 5 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 a total of no more than 5 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 a total of no more than three 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 a total of no more than three 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 a total of no more than two 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 a total of no more than two 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 a total of no more than one 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 a total of no more than one substitution, deletion, and / or insertion in the amino acid sequence set forth in SEQ ID NO: 50.

[0230] 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 a total of no more than 10, 9, 8, 7, 6, 5, 4, 3, 2, 1, or 0 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 a total of no more than 10, 9, 8, 7, 6, 5, 4, 3, 2, 1, or 0 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 a total of no more than 10 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 a total of no more than 10 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 a total of no more than 7 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 a total of no more than 7 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 a total of no more than 5 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 a total of no more than 5 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 a total of no more than three 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 a total of no more than three 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 a total of no more than two 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 a total of no more than two 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 a total of no more than one 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 a total of no more than one substitution, deletion, and / or insertion in the amino acid sequence set forth in SEQ ID NO: 51.

[0231] 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 a total of no more than 10, 9, 8, 7, 6, 5, 4, 3, 2, 1, or 0 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 a total of no more than 10, 9, 8, 7, 6, 5, 4, 3, 2, 1, or 0 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 a total of no more than 10 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 a total of no more than 10 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 a total of no more than 7 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 a total of no more than 7 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 a total of no more than 5 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 a total of no more than 5 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 a total of no more than three 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 a total of no more than three 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 a total of no more than two 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 a total of no more than two 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 a total of no more than one 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 a total of no more than one substitution, deletion, and / or insertion in the amino acid sequence set forth in SEQ ID NO: 52.

[0232] 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 a total of no more than 10, 9, 8, 7, 6, 5, 4, 3, 2, 1, or 0 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 a total of no more than 10, 9, 8, 7, 6, 5, 4, 3, 2, 1, or 0 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 a total of no more than 10 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 a total of no more than 10 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 a total of no more than 7 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 a total of no more than 7 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 a total of no more than 5 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 a total of no more than 5 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 a total of no more than three 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 a total of no more than three 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 a total of no more than two 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 a total of no more than two 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 a total of no more than one 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 a total of no more than one substitution, deletion, and / or insertion in the amino acid sequence set forth in SEQ ID NO: 65.

[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: 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 a total of no more than 10, 9, 8, 7, 6, 5, 4, 3, 2, 1, or 0 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 a total of no more than 10, 9, 8, 7, 6, 5, 4, 3, 2, 1, or 0 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 a total of no more than 10 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 a total of no more than 10 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 a total of no more than 7 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 a total of no more than 7 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 a total of no more than 5 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 a total of no more than 5 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 a total of no more than three 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 a total of no more than three 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 a total of no more than two 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 a total of no more than two 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 a total of no more than one 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 a total of no more than one substitution, deletion, and / or insertion in the amino acid sequence set forth in SEQ ID NO: 66.

[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: 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 a total of no more than 10, 9, 8, 7, 6, 5, 4, 3, 2, 1, or 0 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 a total of no more than 10, 9, 8, 7, 6, 5, 4, 3, 2, 1, or 0 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 a total of no more than 10 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 a total of no more than 10 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 a total of no more than 7 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 a total of no more than 7 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 a total of no more than 5 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 a total of no more than 5 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 a total of no more than three 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 a total of no more than three 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 a total of no more than two 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 a total of no more than two 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 a total of no more than one 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 a total of no more than one substitution, deletion, and / or insertion in the amino acid sequence set forth in SEQ ID NO: 2.

[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: 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 a total of no more than 10, 9, 8, 7, 6, 5, 4, 3, 2, 1, or 0 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 a total of no more than 10, 9, 8, 7, 6, 5, 4, 3, 2, 1, or 0 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 a total of no more than 10 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 a total of no more than 10 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 a total of no more than 7 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 a total of no more than 7 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 a total of no more than 5 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 a total of no more than 5 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 a total of no more than three 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 a total of no more than three substitutions, deletions, and / or insertions in the amino acid sequence set forth in SEQ ID NO: 48. In s...

Claims

1. An antibody or an antigen-binding fragment thereof, wherein the antibody or antigen-binding fragment comprises a heavy chain and a light chain, the heavy chain comprises a heavy chain variable region (HCVR), and the light chain comprises a light chain variable region (LCVR), a) The HCVR comprises a heavy chain complementarity determination region 1 (CDRH1), CDRH2, and CDRH3, wherein CDRH1, CDRH2, and CDRH3 each contain the sequences described in Sequence ID Nos. 3, 41, and 70, respectively. b) An antibody or antigen-binding fragment thereof, wherein the LCVR comprises a light chain complementarity determining region 1 (CDRL1), CDRL2, and CDRL3, and CDRL1, CDRL2, and CDRL3 each contain the sequences described in SEQ ID NOs: 6, 67, and 8, respectively.

2. a) The HCVR contains an amino acid sequence having at least 90%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity with the amino acid sequence described in SEQ ID NO: 72, and the LCVR contains an amino acid sequence having at least 90%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity with the amino acid sequence described in SEQ ID NO: 65, or b) The antibody or antigen-binding fragment according to claim 1, wherein the HCVR comprises the amino acid sequence described 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 described 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.

3. An antibody or antigen-binding fragment according to Claim 1, comprising: (a) a heavy chain including the heavy chain variable region (HCVR) of SEQ ID NO: 72; and (b) a light chain including the light chain variable region (LCVR) of SEQ ID NO:

65.

4. (a) The heavy chain or light chain further includes a steady region, (b) The heavy chain and light chain are linked by a flexible linker to form a single-chain antibody, (c) (i) The LCVR is linked to a light chain constant region containing an amino acid sequence having at least 90%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity with the amino acid sequence described in SEQ ID NO: 62, or (ii) The LCVR is linked to a light chain constant region containing the amino acid sequence described in Sequence ID No. 62, which has 0 to 10 amino acid modifications, such as 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid modifications. (d) (i) The HCVR is linked to a heavy chain constant region containing an amino acid sequence having at least 90%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity with the amino acid sequence described in SEQ ID NO: 76, or (ii) The HCVR is linked to a heavy chain constant region containing the amino acid sequence described in SEQ ID NO: 76, which has 0 to 10 amino acid modifications, such as 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid modifications, or (e) The antibody or its antigen-binding fragment comprises the heavy chain of SEQ ID NO: 83 and the light chain of SEQ ID NO: 86, The antibody or antigen-binding fragment thereof according to claim 1.

5. (a) The HCVR is linked to a heavy chain constant region, and the heavy chain constant region includes an Fc region containing 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), and optionally the Fc region contains aspartic acid (D) (EU index) at position 238, (b) The HCVR is linked to a heavy chain constant region containing an amino acid sequence having at least 90%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity with the amino acid sequence described in SEQ ID NO: 77, or the HCVR is linked to a heavy chain constant region containing an amino acid sequence described 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, and optionally the X at position 121 of SEQ ID NO: 77 is D or P, the X at position 329 of SEQ ID NO: 77 is G or absent, or the X at position 330 of SEQ ID NO: 77 is K or absent. (c) The HCVR is linked to a heavy chain constant region containing an amino acid sequence having at least 90%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity with the amino acid sequence described in SEQ ID NO: 78, or the heavy chain variable region is linked to a heavy chain constant region containing the amino acid sequence described 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, and optionally, the X at position 108 of SEQ ID NO: 78 is S or P, the X at position 326 of SEQ ID NO: 78 is G or absent, or the X at position 327 of SEQ ID NO: 78 is K or absent. (d) The antibody or its antigen-binding fragment is an IgG, IgM, IgE, IgA, or IgD molecule, or is derived from one of these. (e) The antibody or its antigen-binding fragment is an IgG1, IgG2, IgG3, or IgG4 molecule, or is derived from one of these. (f) Whether the antibody is an IgG1 antibody, (g) The antigen-binding fragment is selected from the group consisting of scFv, sc(Fv)2, dsFv, Fab, Fab', (Fab')2, and diabody. The antibody or antigen-binding fragment thereof according to claim 1.

6. (a) The antibody is an IgG1 antibody, and optionally, (1) The IgG1 antibody contains 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), (2) The IgG1 antibody contains one or more modifications selected from 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), (3) The IgG1 antibody is (i) S239D, A330L, and I332E (EU index), (ii) L234A and L235A (EU index), (iii) T250Q and M428L (EU index), (iv) M252Y, S254T, T256E, H433K, and N434F (EU index), (v) E333A (EU Index), (vi) P257I and Q311 (EU index), (vii) K326W and E333S (EU index), (viiii) S239D, I332E, and G236A (EU index), (ix) K322A (EU index), and (x) P238D (EU Index) It includes one or more qualifications selected from, or (4) The IgG1 antibody contains a P238D substitution, (b) The antibody is an IgG2 antibody, and optionally, the IgG2 antibody is derived from a mouse IgG2 antibody, and optionally, the mouse IgG2 antibody includes one or more modifications selected from L235E, E318A, K320A, and K322A (EU index), (c) Whether the antibody is an IgG3 antibody, (d) The antibody is an IgG4 antibody, and is optionally selected (1) The IgG4 antibody contains one or more modifications at positions 228, 234, 235, 327, 329, 330, and 331 (EU index), (2) The IgG4 antibody contains one or more modifications selected from S228P, L234F, L235E, A327G, P329G, A330S, and P331S (EU index), or (3) The IgG4 antibody contains S228P substitution (EU index), The antibody or antigen-binding fragment thereof according to claim 1.

7. (a) The antibody or its antigen-binding fragment binds to the C-terminus or a region adjacent thereto of the extracellular portion of CD200R. The antibody or its antigen-binding fragment binds to a region of 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. The antibody or its antigen-binding fragment binds to a region of approximately 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, and / or When the antibody or its antigen-binding fragment binds to a CD200R molecule on the cell membrane, the antibody or its antigen-binding fragment binds to a region of up to 100 Å, 90 Å, 80 Å, 70 Å, 60 Å, 50 Å, 40 Å, 30 Å, 20 Å, or 10 Å from the cell membrane, (b) The antibody or its antigen-binding fragment binds to a region adjacent to the N-terminus of CD200R, (c) The antibody or its antigen-binding fragment binds to a residue of CD200R selected from T213, E230, and S194, (d) The antibody or its antigen-binding fragment binds to a residue of CD200R selected from T213 and E230, (e) The antibody or its antigen-binding fragment does not bind to cynomolgus monkey CD200RLa, or binds to cynomolgus monkey CD200RLa with a KD of greater than 2 μM as determined by surface plasmon resonance (SPR) at 37°C, and optionally the antibody or its antigen-binding fragment binds to residues T213 and E230 of CD200R, or (f) The antibody or its antigen-binding fragment specifically binds to human CD200R or cynomolgus monkey CD200R, and the antibody or its antigen-binding fragment either does not bind to cynomolgus monkey CD200RLa or binds to cynomolgus monkey CD200RLa with a KD of greater than 2 μM as determined by surface plasmon resonance (SPR) at 37°C, and optionally the antibody or its antigen-binding fragment binds to a residue of CD200R selected from T213 and E230, and optionally the antibody or its antigen-binding fragment binds to residues T213 and E230 of CD200R. The antibody or antigen-binding fragment thereof according to claim 1.

8. (a) The antibody is (i) a monoclonal antibody, (ii) a human or humanized antibody, and / or (iii) a chimeric antibody, (b) The antibody or its antigen-binding fragment agonizes CD200R expressed on the surface of immune cells. (c) When binding to the CD200R of an immune cell, the antibody or its antigen-binding fragment reduces the activation of the immune cell compared to an equivalent immune cell to which the antibody or its antigen-binding fragment is not bound, and / or (d) When binding to the CD200R of an immune cell, the antibody or its antigen-binding fragment reduces the proliferation of the immune cell compared to an equivalent immune cell to which the antibody or its antigen-binding fragment is not bound. The antibody or antigen-binding fragment thereof according to claim 1.

9. (a) The decrease in the activation or proliferation of the immune cells is measured by the assay described in Example 5, 16, or 17. (b) The aforementioned decrease in cell proliferation or activation is measured in vitro or in vivo, and / or (c) The reduction in cell proliferation or activation is at least about 10%, 15%, 20%, 25%, 30%, 40%, or 50%, or 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%. The antibody or antigen-binding fragment thereof according to claim 8.

10. (a) When bound to the CD200R of an immune cell, the antibody or its antigen-binding fragment reduces the expression of inflammatory genes in the immune cell compared to equivalent immune cells to which the antibody or its antigen-binding fragment is not bound. (b) The binding of the antibody or its antigen-binding fragment to the CD200R expressed on the surface of the immune cells reduces the NFκB signaling of the immune cells compared to equivalent immune cells that do not have the antibody or its antigen-binding fragment bound to them, and optionally, the reduction in the NFκB signaling of the immune cells is measured by the assay described in Example 5. (1) The reduction in NFκB signaling of the immune cells is at least about 10%, 15%, 20%, 25%, 30%, or 40%. (2) The reduction in NFκB signaling of the immune cells is approximately 10% to 40%, 10% to 30%, 10% to 20%, 20% to 40%, or 30% to 40%, or (3) The mean maximum inhibition percentage of NFκB signaling in immune cells induced by the antibody or its antigen-binding fragment is at least 20%, 30%, 40%, 50%, or 60% greater than that of the control antibody, (i) A control heavy chain containing CDRH1, CDRH2, and CDRH3, each containing the amino acid sequence described in SEQ ID NOs. 55 to 57, and a control light chain containing CDRL1, CDRL2, and CDRL3, each containing the amino acid sequence described in SEQ ID NOs. 58 to 60, (ii) A control heavy chain variable region containing the amino acid sequence described in SEQ ID NO: 53, and a control light chain variable region containing the amino acid sequence described in SEQ ID NO: 54, or (iii) A control heavy chain sequence containing the amino acid sequence described in SEQ ID NO: 73, and a control light chain sequence containing the amino acid sequence described in SEQ ID NO:

74. including, (c) The immune cells are T cells or monocytes. (d) The antibody or its antigen-binding fragment inhibits the activation of basophils, and optionally, the antibody or its antigen-binding fragment inhibits the activation of basophils induced by FcεRI or inhibits the activation of basophils induced by the binding of IgE to basophils. (e) The antibody or its antigen-binding fragment activates basophils (1) inhibiting by at least 40% or at least 50%, (2) inhibiting by approximately 10% to 90%, 20% to 70%, 30% to 60%, or 40% to 60%, or (3) inhibiting by approximately 10%, 20%, 30%, 40%, 45%, 50%, 55%, 60%, 70%, 80%, or 90%, and / or (f) The inhibition of basophil activation is measured in the assay described in Example 18. The antibody or antigen-binding fragment thereof according to claim 9.

11. (a) The antibody or its antigen-binding fragment does not inhibit the binding of CD200 to CD200R, (b) (i) The antibody or its antigen-binding fragment binds to human CD200R at a KD of less than 10 nM as determined by surface plasmon resonance (SPR) at 37°C, (ii) The antibody or its antigen-binding fragment binds to human CD200R at a KD of less than 5 nM as determined by surface plasmon resonance (SPR) at 37°C, (iii) The antibody or its antigen-binding fragment binds to human CD200R with a KD of less than 2 nM as determined by surface plasmon resonance (SPR) at 37°C, (iv) The antibody or its antigen-binding fragment binds to human CD200R with a KD of less than 1 nM as determined by surface plasmon resonance (SPR) at 37°C, (v) The antibody or its antigen-binding fragment binds to human CD200R at a KD of less than 0.5 nM as determined by surface plasmon resonance (SPR) at 37°C, (vi) The antibody or its antigen-binding fragment binds to cynomolgus monkey CD200R with a KD of less than 100 nM as determined by surface plasmon resonance (SPR) at 37°C, (vii) The antibody or its antigen-binding fragment binds to cynomolgus monkey CD200R with a KD of less than 1 nM as determined by surface plasmon resonance (SPR) at 37°C, (viiii) The antibody or its antigen-binding fragment binds to cynomolgus monkey CD200R with a KD of less than 0.1 nM as determined by surface plasmon resonance (SPR) at 37°C, or (ix) The antibody or its antigen-binding fragment binds to cynomolgus monkey CD200R with a KD of less than 0.01 nM as determined by surface plasmon resonance (SPR) at 37°C. (c) When the antibody or its antigen-binding fragment binds to the CD200R on the surface of an immune cell, the antibody or its antigen-binding fragment does not induce significant cytokine release. (d) The antibody or its antigen-binding fragment comprises a domain that binds to an Fc receptor, optionally the Fc receptor is expressed on the surface of an immune cell, optionally the immune cell is an antigen-presenting cell, optionally the antigen-presenting cell is a dendritic cell, macrophage, monocyte, or neutrophil, optionally the binding of the antibody or its antigen-binding fragment to the Fc receptor expressed on the surface of the immune cell and to CD200R on the surface of a second immune cell is within 250 Å, 200 Å, 150 Å, or 100 Å of the cell surface of the immune cell and the cell surface of the second immune cell, and / or the Fc receptor is FcγRIIB, and / or (e) The antibody or its antigen-binding fragment is bispecific or multispecific, The antibody or antigen-binding fragment thereof according to claim 1.

12. 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 11.

13. 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 11.

14. A host cell comprising one or more nucleic acid molecules encoding heavy chain and light chain amino acid sequences, which, when expressed, can form an antibody or antigen-binding fragment thereof according to any one of claims 1 to 11.

15. (a) To provide a host cell comprising one or more nucleic acid molecules encoding heavy chain and light chain amino acid sequences that, when expressed, can form an antibody or antigen-binding fragment thereof according to any one of claims 1 to 11, (b) Culturing the host cells that express the encoded amino acid sequence, (c) A method comprising isolating the antibody or the antigen-binding fragment thereof.

16. An immunoconjugate comprising an antibody according to any one of claims 1 to 11 or an antigen-binding fragment thereof, conjugated with a drug.

17. A pharmaceutical composition comprising a therapeutically effective amount of the antibody or antigen-binding fragment thereof described in any one of claims 1 to 11.

18. A pharmaceutical composition comprising a therapeutically effective amount of the immunoconjugate described in claim 16 and at least one pharmaceutically acceptable excipient.

19. A composition for therapeutic use, comprising an antibody or antigen-binding fragment thereof as described in any one of claims 1 to 11.

20. A kit comprising in a container an antibody or an antigen-binding fragment thereof according to any one of claims 1 to 11.

21. A kit comprising an immunoconjugate according to claim 16 in a container.

22. A kit comprising the pharmaceutical composition described in Claim 17 in a container.

23. A composition for treating, preventing, alleviating, or reducing the severity of a disease or condition in a subject requiring such treatment, prevention, alleviation, or reduction of its severity, comprising an antibody or antigen-binding fragment containing a heavy chain variable region (HCVR) and a light chain variable region (LCVR), (a) The HCVR includes heavy chain complementarity determination regions 1 (CDRH1), CDRH2, and CDRH3, where CDRH1, CDRH2, and CDRH3 each contain the sequences described in SEQ ID NOs: 3, 41, and 70, respectively, and the LCVR includes light chain complementarity determination regions 1 (CDRL1), CDRL2, and CDRL3, where CDRL1, CDRL2, and CDRL3 each contain the sequences described in SEQ ID NOs: 6, 67, and 8, respectively. (b) The HCVR includes an amino acid sequence having at least 90%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity with the amino acid sequence described in SEQ ID NO: 72, and the LCVR includes an amino acid sequence having at least 90%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity with the amino acid sequence described in SEQ ID NO: 65, or (c) The HCVR includes the amino acid sequence described 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 includes the amino acid sequence described 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. composition.

24. A composition for use in the treatment of a disease or condition, comprising an antibody or antigen-binding fragment thereof according to any one of claims 1 to 11, which specifically binds to CD200R, wherein the antibody or antigen-binding fragment thereof (a) A heavy chain containing the heavy chain variable region (HCVR) of SEQ ID NO: 72 and a light chain containing the light chain variable region (LCVR) of SEQ ID NO: 65, or (b) Heavy chain of SEQ ID NO: 83 and light chain of SEQ ID NO: 86 A composition containing the following:

25. Administering the aforementioned composition (i) Parenteral, intravenous, oral, subcutaneous, intra-arterial, intracranial, intrathecal, intraperitoneal, intratumoral, local, intranasal, or intramuscular administration, (ii) Intravenous, subcutaneous, or intramuscular administration The composition according to claim 23, comprising:

26. The aforementioned disease or condition (a) including diseases or conditions related to the activity or function of CD200R, or (b) Including autoimmune diseases or conditions or inflammatory diseases or conditions, wherein the inflammatory disease or condition is optionally selected from rheumatic diseases or conditions, gastrointestinal diseases or conditions, lung diseases or conditions, liver diseases or conditions, kidney diseases or conditions, and skin conditions, and optionally selected from rheumatic diseases or conditions, (i) A rheumatic disease or condition selected from 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, axial spondyloarthritis not meeting radiographic criteria (nr-AxSpA), polymyositis, Takayasu's arteritis, cutaneous lupus erythematosus (CLE) type: chronic CLE (including discoid), subacute CLE, acute CLE, seroporacosomatic or seroporacosomatic RA, juvenile idiopathic arthritis (JIA), primary or secondary OA, cervical and lumbar OA, hip OA, knee OA, and erosive OA, or (ii) A rheumatic disease or condition selected from rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), lupus nephritis (LN), and osteoarthritis (OA), The composition according to claim 23.

27. The composition according to claim 26, wherein the inflammatory disease or condition is a rheumatic disease or condition, which is rheumatoid arthritis (RA) or systemic lupus erythematosus (SLE).

28. The composition according to claim 27, wherein the inflammatory disease or condition is atopic dermatitis (AD).

29. The composition according to claim 23, wherein the subject is a human subject.

30. The composition according to claim 24, wherein the subject is a human subject.

31. A composition for downregulating the immune response in a target, comprising an antibody or an antigen-binding fragment thereof as described in any one of claims 1 to 11.

32. A composition for downregulating the immune response in a subject, comprising the immune conjugate described in claim 16.

33. The pharmaceutical composition according to claim 17 for downregulating the immune response in a subject.

34. A composition for use in a method for suppressing immune cells expressing CD200R, comprising an antibody or antigen-binding fragment thereof according to any one of claims 1 to 11, wherein the method comprises contacting the immune cells with the antibody or antigen-binding fragment thereof, wherein the immune cells include T cells, B cells, macrophages, or antigen-specific T cells, and / or the subject is a human subject. composition.

35. A composition for use in a method for suppressing immune cells expressing CD200R, comprising the immune conjugate described in claim 16, wherein the method comprises contacting the immune cells with the immune conjugate, optionally comprising T cells, B cells, or macrophages, or antigen-specific T cells, and / or the subject is a human subject. composition.

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