Bifunctional therapeutic antibody targeting the complement cascade

Abstract

The present disclosure relates to, inter alia, compounds (e.g., antibodies or antigen binding fragments thereof, or conjugates thereof) that bind to complement protein 2 (C2), and the use of the compounds in methods for treating or ameliorating one or more symptoms of a disease or disorder associated with the complement pathway.

Description

BPX-05925BIFUNCTIONAL THERAPEUTIC ANTIBODY TARGETING THE COMPLEMENT CASCADERELATED APPLICATIONS

[0001] This application claims the benefit of priority to U.S. Provisional Application No. 63 / 715,147, filed November 1, 2024, the entire contents of which are incorporated by reference.BACKGROUND

[0002] The complement system is a critical component of human host defense with a number of biological effects. A properly functioning complement system is required for protection against infection and for maintaining tissue homeostasis. However, the complement system may also cause damage when the complement system is activated improperly or is not properly regulated.

[0003] The development of effective therapies to treat complement mediated diseases and conditions is complicated by the pathway’s highly diverse and interconnected architecture, making it difficult to identify promising points of therapeutic intervention and to predict clinical study outcomes. Therefore, there is a need for alternate treatments for complement-mediated diseases and conditions which are effective, economical, and decrease patient treatment burden.SUMMARY

[0004] In some aspects, the disclosure provides an antibody, or antigen binding fragment thereof, that specifically binds complement component 2 (C2), wherein the antibody or antigen binding fragment comprises a light chain variable region (VL) and a heavy chain variable region (VH), wherein: the VL comprises a VL complementarity determining region (CDR) 1 (CDRL1) set forth in SEQ ID NO: 1 (XsTFTDIDDDMN), a VL CDR 2 (CDRL2) set forth in SEQ ID NO: 2 (EGNTLRP), and a VL CDR 3 (CDRL3) set forth in SEQ ID NO: 3 (X9QSDNLPFT); and the VH comprises a VH CDR 1 (CDRH1) set forth in SEQ ID NO: 4 (GYTFTDYNMH), a VH CDR 2 (CDRH2) set forth in SEQ ID NO: 5 (YVYPX5IGGTG), and a VH CDR 3 (CDRH3) set forth in SEQ ID NO: 6 (RGYX10GIFDY), wherein X8is I or R; X9is L or Q; X5is Y or S; and X10 is D or E, and wherein at least one of X9 is Q, X5 is S, and X10 is E.

[0005] In some embodiments, the antibody or antigen binding fragment comprises1FH13167949.1BPX-05925(i) the CDRL1 set forth in SEQ ID NO: 8 (RTFTDIDDDMN), the CDRL3 set forth in SEQ ID NO: 9 (LQSDNLPFT), the CDRH2 set forth in SEQ ID NO: 11 (YVYPYIGGTG), and the CDRH3 set forth in SEQ ID NO: 14 (RGYEGIFDY);(ii) the CDRL1 set forth in SEQ ID NO: 8, the CDRL3 set forth in SEQ ID NO: 9, the CDRH2 set forth in SEQ ID NO: 12 (YVYPSIGGTG), and the CDRH3 set forth in SEQ ID NO: 13 (RGYDGIFDY);(hi) the CDRL1 set forth in SEQ ID NO: 8, the CDRL3 set forth in SEQ ID NO: 9, the CDRH2 set forth in SEQ ID NO: 12, and the CDRH3 set forth in SEQ ID NO: 14;(iv) the CDRL1 set forth in SEQ ID NO: 8, the CDRL3 set forth in SEQ ID NO: 10 (QQSDNLPFT), the CDRH2 set forth in SEQ ID NO: 12, and the CDRH3 set forth in SEQ ID NO: 14;(v) the CDRL1 set forth in SEQ ID NO: 7 (ITFTDIDDDMN), the CDRL3 set forth in SEQ ID NO: 9, the CDRH2 set forth in SEQ ID NO: 12, and the CDRH3 set forth in SEQ ID NO: 14;(vi) the CDRL1 set forth in SEQ ID NO: 7, the CDRL3 set forth in SEQ ID NO: 9, the CDRH2 set forth in SEQ ID NO: 11, and the CDRH3 set forth in SEQ ID NO: 14;(vn) the CDRL1 set forth in SEQ ID NO: 7, the CDRL3 set forth in SEQ ID NO: 9, the CDRH2 set forth in SEQ ID NO: 12, and the CDRH3 set forth in SEQ ID NO: 13;(viii) the CDRL1 set forth in SEQ ID NO: 7, the CDRL3 set forth in SEQ ID NO:10, the CDRH2 set forth in SEQ ID NO: 12, and the CDRH3 set forth in SEQ ID NO: 14; or(ix) the CDRL1 set forth in SEQ ID NO: 7, the CDRL3 set forth in SEQ ID NO: 10, the CDRH2 set forth in SEQ ID NO: 12, and the CDRH3 set forth in SEQ ID NO: 13.

[0006] In some aspects, the disclosure provides an antibody, or antigen binding fragment thereof, that specifically binds complement component 2 (C2), wherein the antibody or antigen binding fragment comprises a light chain variable region (VL) and a heavy chain variable region (VH), wherein: the VL comprises a VL complementarity determining region (CDR) 1 (CDRL1) set forth in SEQ ID NO: 184 (X1TX2TDIDDDMN), a VL CDR 2 (CDRL2) set forth in SEQ ID NO: 2 (EGNTLRP), and a VL CDR 3 (CDRL3) set forth in SEQ ID NO: 185 (X3QSDX4LPFT); and the VH comprises a VH CDR 1 (CDRH1) set forth in SEQ ID NO: 4 (GYTFTDYNMH), a VH CDR 2 (CDRH2) set forth in SEQ ID NO: 5 (YVYPX5IGGTG), and a2FH13167949.1BPX-05925VH CDR 3 (CDRH3) set forth in SEQ ID NO: 186 (RGX6X7GIFDY), wherein Xi is I or R; X2is F or H; X3 is L or Q; X4 is N or H; X5 is Y or S; Xs is Y or H; X7 is D or E, and wherein at least one of X3 is Q, X5 is S, and X7 is E.

[0007] In some embodiments, the antibody or antigen binding fragment comprises(1) the CDRL1 set forth in SEQ ID NO: 8 (RTFTDIDDDMN), the CDRL3 set forth in SEQ ID NO: 190 (QQSDHLPFT), the CDRH2 set forth in SEQ ID NO: 12 (YVYPSIGGTG), and the CDRH3 set forth in SEQ ID NO: 14 (RGYEGIFDY);(ii) the CDRL1 set forth in SEQ ID NO: 188 (RTHTDIDDDMN), the CDRL3 set forth in SEQ ID NO: 190, the CDRH2 set forth in SEQ ID NO: 12, and the CDRH3 set forth in SEQ ID NO: 14;(hi) the CDRL1 set forth in SEQ ID NO: 8, the CDRL3 set forth in SEQ ID NO: 190, the CDRH2 set forth in SEQ ID NO: 12, and the CDRH3 set forth in SEQ ID NO: 191 (RGHEGIFDY);(iv) the CDRL1 set forth in SEQ ID NO: 8, the CDRL3 set forth in SEQ ID NO: 189 (LQSDHLPFT), the CDRH2 set forth in SEQ ID NO: 12, and the CDRH3 set forth in SEQ ID NO: 14;(v) the CDRL1 set forth in SEQ ID NO: 8, the CDRL3 set forth in SEQ ID NO: 9 (LQSDNLPFT), the CDRH2 set forth in SEQ ID NO: 12, and the CDRH3 set forth in SEQ ID NO: 14;(vi) the CDRL1 set forth in SEQ ID NO: 8, the CDRL3 set forth in SEQ ID NO: 9, the CDRH2 set forth in SEQ ID NO: 12, and the CDRH3 set forth in SEQ ID NO: 191 ;(vn) the CDRL1 set forth in SEQ ID NO: 8, the CDRL3 set forth in SEQ ID NO: 189, the CDRH2 set forth in SEQ ID NO: 12, and the CDRH3 set forth in SEQ ID NO: 191; or(viii) the CDRL1 set forth in SEQ ID NO: 188, the CDRL3 set forth in SEQ ID NO: 189, the CDRH2 set forth in SEQ ID NO: 12, and the CDRH3 set forth in SEQ ID NO: 14.

[0008] In some embodiments, the VL comprises at least one VL framework region (FR) selected from SEQ ID NOs: 15 (ETTVTQSPSSLSX11SVGX12RVTIX13C), 16 (WYQQKPGKX14PKLLIS), 17 (GVPSRFSXi8SGYGTDFTFTISSMQPEDXi9ATYYC), 18 (FGQGTKLEIK), and 187 (GVPSRFSXI5SGXI6GTDFTFTISSMQPEDXI7ATYYC), wherein Xu is M or A; X12 is D or E; X13 is T or R; X14 is P or A; X15 is S or G; Xi6 is Y or H; X17 is V or F; Xis is S or G; and X19 is V or F.3FH13167949.1BPX-05925

[0009] In some embodiments, the VL comprises at least one VL FR selected from SEQ ID Nos: 15-18.

[0010] In some embodiments, the VL comprises a FR1 region selected from SEQ ID NOs: 23, 24, 25, 26, and 27, a FR2 region selected from SEQ ID NOs: 28 and 29, a FR3 region selected from SEQ ID NOs: 30, 31, 32, 192, and 193, and a FR4 region set forth in SEQ ID NO: 18.

[0011] In some embodiments, the VL comprises a FR1 region selected from SEQ ID Nos: 23, 24, 25, 26, and 27, a FR2 region selected from SEQ ID Nos: 28 and 29, a FR3 region selected from SEQ ID Nos: 30, 31, and 32, and a FR4 region set forth in SEQ ID NO: 18.

[0012] In some embodiments, the VL comprises a FR1 region set forth in SEQ ID NO: 23, a FR2 region set forth in SEQ ID NO: 28, a FR3 region set forth in SEQ ID NO: 30, and a FR4 region set forth in SEQ ID NO: 18.

[0013] In some embodiments, the VL comprises a FR1 region set forth in SEQ ID NO: 23, a FR2 region set forth in SEQ ID NO: 28, a FR3 region set forth in SEQ ID NO: 192, and a FR4 region set forth in SEQ ID NO: 18.

[0014] In some embodiments, the VL comprises a FR1 region set forth in SEQ ID NO: 24, a FR2 region set forth in SEQ ID NO: 28, a FR3 region set forth in SEQ ID NO: 30, and a FR4 region set forth in SEQ ID NO: 18.

[0015] In some embodiments, the VL comprises a FR1 region set forth in SEQ ID NO: 24, a FR2 region set forth in SEQ ID NO: 28, a FR3 region set forth in SEQ ID NO: 192, and a FR4 region set forth in SEQ ID NO: 18.

[0016] In some embodiments, the VL comprises a FR1 region set forth in SEQ ID NO: 24, a FR2 region set forth in SEQ ID NO: 29, a FR3 region set forth in SEQ ID NO: 31, and a FR4 region set forth in SEQ ID NO: 18.

[0017] In some embodiments, the VL comprises a FR1 region set forth in SEQ ID NO: 24, a FR2 region set forth in SEQ ID NO: 29, a FR3 region set forth in SEQ ID NO: 32, and a FR4 region set forth in SEQ ID NO: 18.

[0018] In some embodiments, the VL comprises a FR1 region set forth in SEQ ID NO: 24, a FR2 region set forth in SEQ ID NO: 29, a FR3 region set forth in SEQ ID NO: 193, and a FR4 region set forth in SEQ ID NO: 18.

[0019] In some embodiments, the VH comprises at least one VH FR selected from SEQ ID Nos: 19-22.4FH13167949.1BPX-05925

[0020] In some embodiments, the VH comprises a FR1 region selected from SEQ ID Nos: 33 and 34, a FR2 region set forth in SEQ ID NO: 20, a FR3 region set forth in SEQ ID NO: 21, and a FR4 region set forth in SEQ ID NO: 22.

[0021] In some embodiments, the VH comprises a FR1 region set forth in SEQ ID NO: 33, a FR2 region set forth in SEQ ID NO: 20, a FR3 region set forth in SEQ ID NO: 21, and a FR4 region set forth in SEQ ID NO: 22.

[0022] In some embodiments, the VH comprises a FR1 region set forth in SEQ ID NO: 34, a FR2 region set forth in SEQ ID NO: 20, a FR3 region set forth in SEQ ID NO: 21, and a FR4 region set forth in SEQ ID NO: 22.

[0023] In some embodiments, the VH and the VL comprise amino acid sequences having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequences selected from:(a) SEQ ID NOs: 36 and 50, respectively;(b) SEQ ID NOs: 37 and 50, respectively;(c) SEQ ID NOs: 38 and 50, respectively;(d) SEQ ID NOs: 38 and 51, respectively;(e) SEQ ID NOs: 38 and 52, respectively;(f) SEQ ID NOs: 36 and 40, respectively;(g) SEQ ID NOs: 36 and 41, respectively;(h) SEQ ID NOs: 36 and 42, respectively;(i) SEQ ID NOs: 36 and 43, respectively;(j) SEQ ID NOs: 36 and 44, respectively;(k) SEQ ID NOs: 37 and 40, respectively;(l) SEQ ID NOs: 38 and 40, respectively;(m) SEQ ID NOs: 38 and 41, respectively;(n) SEQ ID NOs: 38 and 45, respectively;(o) SEQ ID NOs: 38 and 46, respectively;(p) SEQ ID NOs: 38 and 47, respectively;(q) SEQ ID NOs: 38 and 48, respectively;(r) SEQ ID NOs: 37 and 46, respectively; and(s) SEQ ID NOs: 37 and 48, respectively.5FH13167949.1BPX-05925

[0024] In some embodiments, the VH and the VL comprise amino acid sequences having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequences selected from:(a) SEQ ID NOs: 36 and 50, respectively;(b) SEQ ID NOs: 37 and 50, respectively;(c) SEQ ID NOs: 38 and 50, respectively;(d) SEQ ID NOs: 38 and 51, respectively;(e) SEQ ID NOs: 38 and 52, respectively;(f) SEQ ID NOs: 36 and 40, respectively;(g) SEQ ID NOs: 36 and 41, respectively;(h) SEQ ID NOs: 36 and 42, respectively;(i) SEQ ID NOs: 36 and 43, respectively;(j) SEQ ID NOs: 36 and 44, respectively;(k) SEQ ID NOs: 37 and 40, respectively;(l) SEQ ID NOs: 38 and 40, respectively;(m) SEQ ID NOs: 38 and 41, respectively;(n) SEQ ID NOs: 38 and 45, respectively;(o) SEQ ID NOs: 38 and 46, respectively;(p) SEQ ID NOs: 38 and 47, respectively;(q) SEQ ID NOs: 38 and 48, respectively;(r) SEQ ID NOs: 37 and 46, respectively;(s) SEQ ID NOs: 37 and 48, respectively;(t) SEQ ID NOs: 38 and 195, respectively;(u) SEQ ID NOs: 38 and 196, respectively;(v) SEQ ID NOs: 38 and 197, respectively;(w) SEQ ID NOs: 194 and 41, respectively;(x) SEQ ID NOs: 194 and 195, respectively;(y) SEQ ID NOs: 38 and 198, respectively;(z) SEQ ID NOs: 38 and 199, respectively;(aa) SEQ ID NOs: 194 and 197, respectively;(bb) SEQ ID NOs: 38 and 200, respectively;6FH13167949.1BPX-05925(cc) SEQ ID NOs: 38 and 201, respectively;(dd) SEQ ID NOs: 194 and 200, respectively;(ee) SEQ ID NOs: 38 and 202, respectively;(ff) SEQ ID NOs: 38 and 203, respectively; and(gg) SEQ ID NOs: 194 and 202, respectively.

[0025] In some embodiments, the VH and the VL comprise the amino acid sequences selected from:(a) SEQ ID NOs: 36 and 50, respectively;(b) SEQ ID NOs: 37 and 50, respectively;(c) SEQ ID NOs: 38 and 50, respectively;(d) SEQ ID NOs: 38 and 51, respectively;(e) SEQ ID NOs: 38 and 52, respectively;(f) SEQ ID NOs: 36 and 40, respectively;(g) SEQ ID NOs: 36 and 41, respectively;(h) SEQ ID NOs: 36 and 42, respectively;(i) SEQ ID NOs: 36 and 43, respectively;(j) SEQ ID NOs: 36 and 44, respectively;(k) SEQ ID NOs: 37 and 40, respectively;(l) SEQ ID NOs: 38 and 40, respectively;(m) SEQ ID NOs: 38 and 41, respectively;(n) SEQ ID NOs: 38 and 45, respectively;(o) SEQ ID NOs: 38 and 46, respectively;(p) SEQ ID NOs: 38 and 47, respectively;(q) SEQ ID NOs: 38 and 48, respectively;(r) SEQ ID NOs: 37 and 46, respectively; and(s) SEQ ID NOs: 37 and 48, respectively.

[0026] In some embodiments, the VH and the VL comprise the amino acid sequences selected from:(a) SEQ ID NOs: 36 and 50, respectively;(b) SEQ ID NOs: 37 and 50, respectively;(c) SEQ ID NOs: 38 and 50, respectively;7FH13167949.1BPX-05925(d) SEQ ID NOs: 38 and 51, respectively;(e) SEQ ID NOs: 38 and 52, respectively;(f) SEQ ID NOs: 36 and 40, respectively;(g) SEQ ID NOs: 36 and 41, respectively;(h) SEQ ID NOs: 36 and 42, respectively;(i) SEQ ID NOs: 36 and 43, respectively;(j) SEQ ID NOs: 36 and 44, respectively;(k) SEQ ID NOs: 37 and 40, respectively;(l) SEQ ID NOs: 38 and 40, respectively;(m) SEQ ID NOs: 38 and 41, respectively;(n) SEQ ID NOs: 38 and 45, respectively;(o) SEQ ID NOs: 38 and 46, respectively;(p) SEQ ID NOs: 38 and 47, respectively;(q) SEQ ID NOs: 38 and 48, respectively;(r) SEQ ID NOs: 37 and 46, respectively;(s) SEQ ID NOs: 37 and 48, respectively;(t) SEQ ID NOs: 38 and 195, respectively;(u) SEQ ID NOs: 38 and 196, respectively;(v) SEQ ID NOs: 38 and 197, respectively;(w) SEQ ID NOs: 194 and 41, respectively;(x) SEQ ID NOs: 194 and 195, respectively;(y) SEQ ID NOs: 38 and 198, respectively;(z) SEQ ID NOs: 38 and 199, respectively;(aa) SEQ ID NOs: 194 and 197, respectively;(bb) SEQ ID NOs: 38 and 200, respectively;(cc) SEQ ID NOs: 38 and 201, respectively;(dd) SEQ ID NOs: 194 and 200, respectively;(ee) SEQ ID NOs: 38 and 202, respectively;(ff) SEQ ID NOs: 38 and 203, respectively; and(gg) SEQ ID NOs: 194 and 202, respectively.8FH13167949.1BPX-05925

[0027] In some aspects, the disclosure provides an antibody, or antigen binding fragment thereof, that specifically binds complement component 2 (C2), wherein the antibody or antigen binding fragment comprises:(i) a VL comprising:(a) a CDRL1 set forth in SEQ ID NO: 184 (XITX2TDIDDDMN), wherein Xi is I or R; X2is F or H;(b) a CDRL2 set forth in SEQ ID NO: 2 (EGNTLRP);(c) a CDRL3 set forth in SEQ ID NO: 185 (X3QSDX4LPFT), wherein X3is L or Q; X4 is N or H;(d) a VL FR1 comprising an amino acid sequence having at least 95% identity to SEQ ID NO: 15 (ETTVTQSPSSLSXHSVGXI2RVTIXI3C), wherein Xu is M or A; Xi2is D or E; Xi3is T or R;(e) a VL FR2 comprising an amino acid sequence having at least 95% identity to SEQ ID NO: 16 (WYQQKPGKX14PKLLIS), wherein Xi4is P or A;(f) a VL FR3 comprising an amino acid sequence having at least 95% identity to SEQ ID NO: 187 (GVPSRFSXI5SGXI6GTDFTFTISSMQPEDXI7ATYYC), wherein X15 is S or G; Xi6 is Y or H; X17 is V or F;(g) a VL FR4 comprising an amino acid sequence having at least 95% identity to SEQ ID NO: 18 (FGQGTKLEIK); and(ii) a VH comprising:(A) a CDRH1 set forth in SEQ ID NO: 4 (GYTFTDYNMH);(B) a CDRH2 set forth in SEQ ID NO: 5 (YVYPX5IGGTG), wherein X5is Y or S;(C) a CDRH3 set forth in SEQ ID NO: 186 (RGX6X7GIFDY), wherein Xe is Y or H; X7 is D or E;(D) a VH FR1 comprising an amino acid sequence having at least 95% identity to SEQ ID NO: 19 (X20VQLVQSGAEVKKPGASVKISCKAS), wherein X20is E or Q;(E) a VH FR2 comprising an amino acid sequence having at least 95% identity to SEQ ID NO: 20 (WVRQAPGQGLEWIG);(F) a VH FR3 comprising an amino acid sequence having at least 95% identity to SEQ ID NO: 21 (YNQKFKNRATLTVDTSTSTAYMELSSLRSEDTAVYYCTR); and9FH13167949.1BPX-05925(G) a VH FR4 comprising an amino acid sequence having at least 95% identity to SEQ ID NO: 22 (WGQGTTLTVSS).

[0028] In some aspects, the disclosure provides an antibody, or antigen binding fragment thereof, that specifically binds complement component 2 (C2), wherein the antibody or antigen binding fragment comprises:(i) a VL comprising:(a) a CDRL1 set forth in SEQ ID NO: 1 (XsTFTDIDDDMN), wherein X8is I or R;(b) a CDRL2 set forth in SEQ ID NO: 2 (EGNTLRP);(c) a CDRL3 set forth in SEQ ID NO: 3 (X9QSDNLPFT), wherein X9is L or Q;(d) a VL FR1 comprising an amino acid sequence having at least 95% identity to SEQ ID NO: 15 (ETTVTQSPSSLSX11SVGX12RVTIX13C), wherein Xu is M or A; X12 is D or E; X13 is T or R;(e) a VL FR2 comprising an amino acid sequence having at least 95% identity to SEQ ID NO: 16 (WYQQKPGKX14PKLLIS), wherein Xi4is P or A;(f) a VL FR3 comprising an amino acid sequence having at least 95% identity to SEQ ID NO: 17 (GVPSRFSXI XSGYGTDFTFTISSMQPEDXI 9ATYYC), wherein Xis is S or G; X19 is V or F; and(g) a VL FR4 comprising an amino acid sequence having at least 95% identity to SEQ ID NO: 18 (FGQGTKLEIK); and(ii) a VH comprising:(A) a CDRH1 set forth in SEQ ID NO: 4 (GYTFTDYNMH);(B) a CDRH2 set forth in SEQ ID NO: 5 (YVYPX5IGGTG), wherein X5is Y or S;(C) a CDRH3 set forth in SEQ ID NO: 6 (RGYX10GIFDY), wherein X10 is D or E;(D) a VH FR1 comprising an amino acid sequence having at least 95% identity to SEQ ID NO: 19 (X20VQLVQSGAEVKKPGASVKISCKAS), wherein X20 is E or Q;10FH13167949.1BPX-05925(E) a VH FR2 comprising an amino acid sequence having at least 95% identity to SEQ ID NO: 20 (WVRQAPGQGLEWIG);(F) a VH FR3 comprising an amino acid sequence having at least 95% identity to SEQ ID NO: 21( YNQKFKNRATLTVDTSTS TAYMELS SLRSEDT AVYYCTR) ; and(G) a VH FR4 comprising an amino acid sequence having at least 95% identity to SEQ ID NO: 22 (WGQGTTLTVSS).

[0029] In some embodiments,(i) the VL comprises:(a) the CDRL1 set forth in SEQ ID NO: 7 (ITFTDIDDDMN);(c) the CDRL3 set forth in SEQ ID NO: 9 (LQSDNLPFT);(d) the VL FR1 set forth in SEQ ID NO: 23 (ETTVTQSPS SLSMS VGDRVTITC) ;(e) the VL FR2 set forth in SEQ ID NO: 28 (WYQQKPGKPPKLLIS);(f) the VL FR3 set forth in SEQ ID NO: 30(GVPSRF S S SGYGTDFTFTIS SMQPED VATYYC) ; and(g) the VL FR4 set forth in SEQ ID NO: 18; and(ii) the VH comprises:(B) the CDRH2 set forth in SEQ ID NO: 11 (YVYPYIGGTG);(C) the CDRH3 set forth in SEQ ID NO: 13 (RGYDGIFDY);(D) the VH FR1 set forth in SEQ ID NO: 33 (EVQLVQSGAEVKKPGASVKISCKAS);(E) the VH FR2 set forth in SEQ ID NO: 20;(F) the VH FR3 set forth in SEQ ID NO: 21 ; and(G) the VH FR4 set forth in SEQ ID NO: 22.

[0030] In some embodiments:(i) the VL comprises:(a) the CDRL1 set forth in SEQ ID NO: 7;(c) the CDRL3 set forth in SEQ ID NO: 9;(d) the VL FR1 set forth in SEQ ID NO: 23;(e) the VL FR2 set forth in SEQ ID NO: 28;11FH13167949.1BPX-05925(f) the VL FR3 set forth in SEQ ID NO: 30; and(g) the VL FR4 set forth in SEQ ID NO: 18; and(ii) the VH comprises:(B) the CDRH2 set forth in SEQ ID NO: 11 ;(C) the CDRH3 set forth in SEQ ID NO: 13;(D) the VH FR1 set forth in SEQ ID NO: 34(QVQLVQSGAEVKKPGASVKISCKAS);(E) the VH FR2 set forth in SEQ ID NO: 20;(F) the VH FR3 set forth in SEQ ID NO: 21 ; and(G) the VH FR4 set forth in SEQ ID NO: 22.

[0031] In some embodiments:(i) the VL comprises:(a) the CDRL1 set forth in SEQ ID NO: 7;(c) the CDRL3 set forth in SEQ ID NO: 9;(d) the VL FR1 set forth in SEQ ID NO: 24(ETTVTQSPS SLS AS VGDRVTITC) ;(e) the VL FR2 set forth in SEQ ID NO: 29 (WYQQKPGKAPKLLIS);(f) the VL FR3 set forth in SEQ ID NO: 31(GVPSRFSSSGYGTDFTFTISSMQPEDFATYYC); and(g) the VL FR4 set forth in SEQ ID NO: 18; and(ii) the VH comprises:(B) the CDRH2 set forth in SEQ ID NO: 11 ;(C) the CDRH3 set forth in SEQ ID NO: 13;(D) the VH FR1 set forth in SEQ ID NO: 33;(E) the VH FR2 set forth in SEQ ID NO: 20;(F) the VH FR3 set forth in SEQ ID NO: 21 ; and(G) the VH FR4 set forth in SEQ ID NO: 22.

[0032] In some embodiments:(i) the VL comprises:(a) the CDRL1 set forth in SEQ ID NO: 8 (RTFTDIDDDMN);(c) the CDRL3 set forth in SEQ ID NO: 9;12FH13167949.1BPX-05925(d) the VL FR1 set forth in SEQ ID NO: 24;(e) the VL FR2 set forth in SEQ ID NO: 29;(f) the VL FR3 set forth in SEQ ID NO: 32 (GVPSRFSGSGYGTDFTFTISSMQPEDFATYYC); and(g) the VL FR4 set forth in SEQ ID NO: 18; and(ii) the VH comprises:(B) the CDRH2 set forth in SEQ ID NO: 11 ;(C) the CDRH3 set forth in SEQ ID NO: 13;(D) the VH FR1 set forth in SEQ ID NO: 33;(E) the VH FR2 set forth in SEQ ID NO: 20;(F) the VH FR3 set forth in SEQ ID NO: 21 ; and(G) the VH FR4 set forth in SEQ ID NO: 22.

[0033] In some embodiments:(i) the VL comprises:(a) the CDRL1 set forth in SEQ ID NO: 8;(c) the CDRL3 set forth in SEQ ID NO: 9;(d) the VL FR1 set forth in SEQ ID NO: 23;(e) the VL FR2 set forth in SEQ ID NO: 28;(f) the VL FR3 set forth in SEQ ID NO: 30; and(g) the VL FR4 set forth in SEQ ID NO: 18; and(ii) the VH comprises:(B) the CDRH2 set forth in SEQ ID NO: 11 ;(C) the CDRH3 set forth in SEQ ID NO: 13;(D) the VH FR1 set forth in SEQ ID NO: 33;(E) the VH FR2 set forth in SEQ ID NO: 20;(F) the VH FR3 set forth in SEQ ID NO: 21 ; and(G) the VH FR4 set forth in SEQ ID NO: 22.

[0034] In some embodiments:(i) the VL comprises:(a) the CDRL1 set forth in SEQ ID NO: 8;(c) the CDRL3 set forth in SEQ ID NO: 9;13FH13167949.1BPX-05925(d) the VL FR1 set forth in SEQ ID NO: 24;(e) the VL FR2 set forth in SEQ ID NO: 29;(f) the VL FR3 set forth in SEQ ID NO: 32; and(g) the VL FR4 set forth in SEQ ID NO: 18; and(ii) the VH comprises:(B) the CDRH2 set forth in SEQ ID NO: 11 ;(C) the CDRH3 set forth in SEQ ID NO: 14;(D) the VH FR1 set forth in SEQ ID NO: 33;(E) the VH FR2 set forth in SEQ ID NO: 20;(F) the VH FR3 set forth in SEQ ID NO: 21 ; and(G) the VH FR4 set forth in SEQ ID NO: 22.

[0035] In some embodiments:(i) the VL comprises:(a) the CDRL1 set forth in SEQ ID NO: 8;(c) the CDRL3 set forth in SEQ ID NO: 9;(d) the VL FR1 set forth in SEQ ID NO: 24;(e) the VL FR2 set forth in SEQ ID NO: 29;(f) the VL FR3 set forth in SEQ ID NO: 32; and(g) the VL FR4 set forth in SEQ ID NO: 18; and(ii) the VH comprises:(B) the CDRH2 set forth in SEQ ID NO: 12;(C) the CDRH3 set forth in SEQ ID NO: 13;(D) the VH FR1 set forth in SEQ ID NO: 33;(E) the VH FR2 set forth in SEQ ID NO: 20;(F) the VH FR3 set forth in SEQ ID NO: 21 ; and(G) the VH FR4 set forth in SEQ ID NO: 22.

[0036] In some embodiments:(i) the VL comprises:(a) the CDRL1 set forth in SEQ ID NO: 8;(c) the CDRL3 set forth in SEQ ID NO: 9;(d) the VL FR1 set forth in SEQ ID NO: 24;14FH13167949.1BPX-05925(e) the VL FR2 set forth in SEQ ID NO: 29;(f) the VL FR3 set forth in SEQ ID NO: 32; and(g) the VL FR4 set forth in SEQ ID NO: 18; and(ii) the VH comprises:(B) the CDRH2 set forth in SEQ ID NO: 12;(C) the CDRH3 set forth in SEQ ID NO: 14;(D) the VH FR1 set forth in SEQ ID NO: 33;(E) the VH FR2 set forth in SEQ ID NO: 20;(F) the VH FR3 set forth in SEQ ID NO: 21 ; and(G) the VH FR4 set forth in SEQ ID NO: 22.

[0037] In some embodiments:(i) the VL comprises:(a) the CDRL1 set forth in SEQ ID NO: 8;(c) the CDRL3 set forth in SEQ ID NO: 10;(d) the VL FR1 set forth in SEQ ID NO: 24;(e) the VL FR2 set forth in SEQ ID NO: 29;(f) the VL FR3 set forth in SEQ ID NO: 32; and(g) the VL FR4 set forth in SEQ ID NO: 18; and(ii) the VH comprises:(B) the CDRH2 set forth in SEQ ID NO: 12;(C) the CDRH3 set forth in SEQ ID NO: 14;(D) the VH FR1 set forth in SEQ ID NO: 33;(E) the VH FR2 set forth in SEQ ID NO: 20;(F) the VH FR3 set forth in SEQ ID NO: 21 ; and(G) the VH FR4 set forth in SEQ ID NO: 22.

[0038] In some embodiments:(i) the VL comprises:(a) the CDRL1 set forth in SEQ ID NO: 7;(c) the CDRL3 set forth in SEQ ID NO: 9;(d) the VL FR1 set forth in SEQ ID NO: 24;(e) the VL FR2 set forth in SEQ ID NO: 29;15FH13167949.1BPX-05925(f) the VL FR3 set forth in SEQ ID NO: 32; and(g) the VL FR4 set forth in SEQ ID NO: 18; and(ii) the VH comprises:(B) the CDRH2 set forth in SEQ ID NO: 12;(C) the CDRH3 set forth in SEQ ID NO: 14;(D) the VH FR1 set forth in SEQ ID NO: 33;(E) the VH FR2 set forth in SEQ ID NO: 20;(F) the VH FR3 set forth in SEQ ID NO: 21 ; and(G) the VH FR4 set forth in SEQ ID NO: 22.

[0039] In some embodiments:(i) the VL comprises:(a) the CDRL1 set forth in SEQ ID NO: 7;(c) the CDRL3 set forth in SEQ ID NO: 9;(d) the VL FR1 set forth in SEQ ID NO: 23;(e) the VL FR2 set forth in SEQ ID NO: 28;(f) the VL FR3 set forth in SEQ ID NO: 30; and(g) the VL FR4 set forth in SEQ ID NO: 18; and(ii) the VH comprises:(B) the CDRH2 set forth in SEQ ID NO: 11 ;(C) the CDRH3 set forth in SEQ ID NO: 14;(D) the VH FR1 set forth in SEQ ID NO: 33;(E) the VH FR2 set forth in SEQ ID NO: 20;(F) the VH FR3 set forth in SEQ ID NO: 21 ; and(G) the VH FR4 set forth in SEQ ID NO: 22.

[0040] In some embodiments:(i) the VL comprises:(a) the CDRL1 set forth in SEQ ID NO: 8;(c) the CDRL3 set forth in SEQ ID NO: 9;(d) the VL FR1 set forth in SEQ ID NO: 23;(e) the VL FR2 set forth in SEQ ID NO: 28;(f) the VL FR3 set forth in SEQ ID NO: 30; and16FH13167949.1BPX-05925(g) the VL FR4 set forth in SEQ ID NO: 18; and(ii) the VH comprises:(B) the CDRH2 set forth in SEQ ID NO: 11 ;(C) the CDRH3 set forth in SEQ ID NO: 14;(D) the VH FR1 set forth in SEQ ID NO: 33;(E) the VH FR2 set forth in SEQ ID NO: 20;(F) the VH FR3 set forth in SEQ ID NO: 21 ; and(G) the VH FR4 set forth in SEQ ID NO: 22.

[0041] In some embodiments:(i) the VL comprises:(a) the CDRL1 set forth in SEQ ID NO: 7;(c) the CDRL3 set forth in SEQ ID NO: 9;(d) the VL FR1 set forth in SEQ ID NO: 25;(e) the VL FR2 set forth in SEQ ID NO: 28;(f) the VL FR3 set forth in SEQ ID NO: 30; and(g) the VL FR4 set forth in SEQ ID NO: 18; and(ii) the VH comprises:(B) the CDRH2 set forth in SEQ ID NO: 11 ;(C) the CDRH3 set forth in SEQ ID NO: 14;(D) the VH FR1 set forth in SEQ ID NO: 33;(E) the VH FR2 set forth in SEQ ID NO: 20;(F) the VH FR3 set forth in SEQ ID NO: 21 ; and(G) the VH FR4 set forth in SEQ ID NO: 22.

[0042] In some embodiments:(i) the VL comprises:(a) the CDRL1 set forth in SEQ ID NO: 7;(c) the CDRL3 set forth in SEQ ID NO: 9;(d) the VL FR1 set forth in SEQ ID NO: 26;(e) the VL FR2 set forth in SEQ ID NO: 28;(f) the VL FR3 set forth in SEQ ID NO: 30; and(g) the VL FR4 set forth in SEQ ID NO: 18; and17FH13167949.1BPX-05925(ii) the VH comprises:(B) the CDRH2 set forth in SEQ ID NO: 11 ;(C) the CDRH3 set forth in SEQ ID NO: 14;(D) the VH FR1 set forth in SEQ ID NO: 33;(E) the VH FR2 set forth in SEQ ID NO: 20;(F) the VH FR3 set forth in SEQ ID NO: 21 ; and(G) the VH FR4 set forth in SEQ ID NO: 22.

[0043] In some embodiments:(i) the VL comprises:(a) the CDRL1 set forth in SEQ ID NO: 7;(c) the CDRL3 set forth in SEQ ID NO: 9;(d) the VL FR1 set forth in SEQ ID NO: 27;(e) the VL FR2 set forth in SEQ ID NO: 28;(f) the VL FR3 set forth in SEQ ID NO: 30; and(g) the VL FR4 set forth in SEQ ID NO: 18; and(ii) the VH comprises:(B) the CDRH2 set forth in SEQ ID NO: 11 ;(C) the CDRH3 set forth in SEQ ID NO: 14;(D) the VH FR1 set forth in SEQ ID NO: 33;(E) the VH FR2 set forth in SEQ ID NO: 20;(F) the VH FR3 set forth in SEQ ID NO: 21 ; and(G) the VH FR4 set forth in SEQ ID NO: 22.

[0044] In some embodiments:(i) the VL comprises:(a) the CDRL1 set forth in SEQ ID NO: 7;(c) the CDRL3 set forth in SEQ ID NO: 9;(d) the VL FR1 set forth in SEQ ID NO: 23;(e) the VL FR2 set forth in SEQ ID NO: 28;(f) the VL FR3 set forth in SEQ ID NO: 30; and(g) the VL FR4 set forth in SEQ ID NO: 18; and(ii) the VH comprises:18FH13167949.1BPX-05925(B) the CDRH2 set forth in SEQ ID NO: 12;(C) the CDRH3 set forth in SEQ ID NO: 13;(D) the VH FR1 set forth in SEQ ID NO: 33;(E) the VH FR2 set forth in SEQ ID NO: 20;(F) the VH FR3 set forth in SEQ ID NO: 21 ; and(G) the VH FR4 set forth in SEQ ID NO: 22.

[0045] In some embodiments:(i) the VL comprises:(a) the CDRL1 set forth in SEQ ID NO: 7;(c) the CDRL3 set forth in SEQ ID NO: 9;(d) the VL FR1 set forth in SEQ ID NO: 23;(e) the VL FR2 set forth in SEQ ID NO: 28;(f) the VL FR3 set forth in SEQ ID NO: 30; and(g) the VL FR4 set forth in SEQ ID NO: 18; and(ii) the VH comprises:(B) the CDRH2 set forth in SEQ ID NO: 12;(C) the CDRH3 set forth in SEQ ID NO: 14;(D) the VH FR1 set forth in SEQ ID NO: 33;(E) the VH FR2 set forth in SEQ ID NO: 20;(F) the VH FR3 set forth in SEQ ID NO: 21 ; and(G) the VH FR4 set forth in SEQ ID NO: 22.

[0046] In some embodiments:(i) the VL comprises:(a) the CDRL1 set forth in SEQ ID NO: 8;(c) the CDRL3 set forth in SEQ ID NO: 9;(d) the VL FR1 set forth in SEQ ID NO: 23;(e) the VL FR2 set forth in SEQ ID NO: 28;(f) the VL FR3 set forth in SEQ ID NO: 30; and(g) the VL FR4 set forth in SEQ ID NO: 18; and(ii) the VH comprises:(B) the CDRH2 set forth in SEQ ID NO: 12;19FH13167949.1BPX-05925(C) the CDRH3 set forth in SEQ ID NO: 14;(D) the VH FR1 set forth in SEQ ID NO: 33;(E) the VH FR2 set forth in SEQ ID NO: 20;(F) the VH FR3 set forth in SEQ ID NO: 21 ; and(G) the VH FR4 set forth in SEQ ID NO: 22.

[0047] In some embodiments:(i) the VL comprises:(a) the CDRL1 set forth in SEQ ID NO: 8;(c) the CDRL3 set forth in SEQ ID NO: 9;(d) the VL FR1 set forth in SEQ ID NO: 24;(e) the VL FR2 set forth in SEQ ID NO: 28;(f) the VL FR3 set forth in SEQ ID NO: 30; and(g) the VL FR4 set forth in SEQ ID NO: 18; and(ii) the VH comprises:(B) the CDRH2 set forth in SEQ ID NO: 12;(C) the CDRH3 set forth in SEQ ID NO: 14;(D) the VH FR1 set forth in SEQ ID NO: 33;(E) the VH FR2 set forth in SEQ ID NO: 20;(F) the VH FR3 set forth in SEQ ID NO: 21 ; and(G) the VH FR4 set forth in SEQ ID NO: 22.

[0048] In some embodiments:(i) the VL comprises:(a) the CDRL1 set forth in SEQ ID NO: 7;(c) the CDRL3 set forth in SEQ ID NO: 9;(d) the VL FR1 set forth in SEQ ID NO: 24;(e) the VL FR2 set forth in SEQ ID NO: 28;(f) the VL FR3 set forth in SEQ ID NO: 30; and(g) the VL FR4 set forth in SEQ ID NO: 18; and(ii) the VH comprises:(B) the CDRH2 set forth in SEQ ID NO: 12;(C) the CDRH3 set forth in SEQ ID NO: 14;20FH13167949.1BPX-05925(D) the VH FR1 set forth in SEQ ID NO: 33;(E) the VH FR2 set forth in SEQ ID NO: 20;(F) the VH FR3 set forth in SEQ ID NO: 21 ; and(G) the VH FR4 set forth in SEQ ID NO: 22.

[0049] In some embodiments:(i) the VL comprises:(a) the CDRL1 set forth in SEQ ID NO: 8;(c) the CDRL3 set forth in SEQ ID NO: 10;(d) the VL FR1 set forth in SEQ ID NO: 24;(e) the VL FR2 set forth in SEQ ID NO: 28;(f) the VL FR3 set forth in SEQ ID NO: 30; and(g) the VL FR4 set forth in SEQ ID NO: 18; and(ii) the VH comprises:(B) the CDRH2 set forth in SEQ ID NO: 12;(C) the CDRH3 set forth in SEQ ID NO: 14;(D) the VH FR1 set forth in SEQ ID NO: 33;(E) the VH FR2 set forth in SEQ ID NO: 20;(F) the VH FR3 set forth in SEQ ID NO: 21 ; and(G) the VH FR4 set forth in SEQ ID NO: 22.

[0050] In some embodiments:(i) the VL comprises:(a) the CDRL1 set forth in SEQ ID NO: 7;(c) the CDRL3 set forth in SEQ ID NO: 10;(d) the VL FR1 set forth in SEQ ID NO: 24;(e) the VL FR2 set forth in SEQ ID NO: 28;(f) the VL FR3 set forth in SEQ ID NO: 30; and(g) the VL FR4 set forth in SEQ ID NO: 18; and(ii) the VH comprises:(B) the CDRH2 set forth in SEQ ID NO: 12;(C) the CDRH3 set forth in SEQ ID NO: 14;(D) the VH FR1 set forth in SEQ ID NO: 33;21FH13167949.1BPX-05925(E) the VH FR2 set forth in SEQ ID NO: 20;(F) the VH FR3 set forth in SEQ ID NO: 21 ; and(G) the VH FR4 set forth in SEQ ID NO: 22.

[0051] In some embodiments:(i) the VL comprises:(a) the CDRL1 set forth in SEQ ID NO: 7;(c) the CDRL3 set forth in SEQ ID NO: 9;(d) the VL FR1 set forth in SEQ ID NO: 24;(e) the VL FR2 set forth in SEQ ID NO: 28;(f) the VL FR3 set forth in SEQ ID NO: 30; and(g) the VL FR4 set forth in SEQ ID NO: 18; and(ii) the VH comprises:(B) the CDRH2 set forth in SEQ ID NO: 11 ;(C) the CDRH3 set forth in SEQ ID NO: 13;(D) the VH FR1 set forth in SEQ ID NO: 33;(E) the VH FR2 set forth in SEQ ID NO: 20;(F) the VH FR3 set forth in SEQ ID NO: 21 ; and(G) the VH FR4 set forth in SEQ ID NO: 22.

[0052] In some embodiments:(i) the VL comprises:(a) the CDRL1 set forth in SEQ ID NO: 7;(c) the CDRL3 set forth in SEQ ID NO: 9;(d) the VL FR1 set forth in SEQ ID NO: 24;(e) the VL FR2 set forth in SEQ ID NO: 28;(f) the VL FR3 set forth in SEQ ID NO: 30; and(g) the VL FR4 set forth in SEQ ID NO: 18; and(ii) the VH comprises:(B) the CDRH2 set forth in SEQ ID NO: 12;(C) the CDRH3 set forth in SEQ ID NO: 13;(D) the VH FR1 set forth in SEQ ID NO: 33;(E) the VH FR2 set forth in SEQ ID NO: 20;22FH13167949.1BPX-05925(F) the VH FR3 set forth in SEQ ID NO: 21 ; and(G) the VH FR4 set forth in SEQ ID NO: 22.

[0053] In some embodiments:(i) the VL comprises:(a) the CDRL1 set forth in SEQ ID NO: 7;(c) the CDRL3 set forth in SEQ ID NO: 10;(d) the VL FR1 set forth in SEQ ID NO: 24;(e) the VL FR2 set forth in SEQ ID NO: 28;(f) the VL FR3 set forth in SEQ ID NO: 30; and(g) the VL FR4 set forth in SEQ ID NO: 18; and(ii) the VH comprises:(B) the CDRH2 set forth in SEQ ID NO: 12;(C) the CDRH3 set forth in SEQ ID NO: 13;(D) the VH FR1 set forth in SEQ ID NO: 33;(E) the VH FR2 set forth in SEQ ID NO: 20;(F) the VH FR3 set forth in SEQ ID NO: 21 ; and(G) the VH FR4 set forth in SEQ ID NO: 22.

[0054] In some embodiments:(i) the VL comprises:(a) the CDRL1 set forth in SEQ ID NO: 8;(c) the CDRL3 set forth in SEQ ID NO: 190;(d) the VL FR1 set forth in SEQ ID NO: 24;(e) the VL FR2 set forth in SEQ ID NO: 28;(f) the VL FR3 set forth in SEQ ID NO: 192; and(g) the VL FR4 set forth in SEQ ID NO: 18; and(ii) the VH comprises:(B) the CDRH2 set forth in SEQ ID NO: 12;(C) the CDRH3 set forth in SEQ ID NO: 14;(D) the VH FR1 set forth in SEQ ID NO: 33;(E) the VH FR2 set forth in SEQ ID NO: 20;(F) the VH FR3 set forth in SEQ ID NO: 21 ; and23FH13167949.1BPX-05925(G) the VH FR4 set forth in SEQ ID NO: 22.

[0055] In some embodiments:(i) the VL comprises:(a) the CDRL1 set forth in SEQ ID NO: 188;(c) the CDRL3 set forth in SEQ ID NO: 190;(d) the VL FR1 set forth in SEQ ID NO: 24;(e) the VL FR2 set forth in SEQ ID NO: 28;(f) the VL FR3 set forth in SEQ ID NO: 192; and(g) the VL FR4 set forth in SEQ ID NO: 18; and(ii) the VH comprises:(B) the CDRH2 set forth in SEQ ID NO: 12;(C) the CDRH3 set forth in SEQ ID NO: 14;(D) the VH FR1 set forth in SEQ ID NO: 33;(E) the VH FR2 set forth in SEQ ID NO: 20;(F) the VH FR3 set forth in SEQ ID NO: 21 ; and(G) the VH FR4 set forth in SEQ ID NO: 22.

[0056] In some embodiments:(i) the VL comprises:(a) the CDRL1 set forth in SEQ ID NO: 8;(c) the CDRL3 set forth in SEQ ID NO: 190;(d) the VL FR1 set forth in SEQ ID NO: 24;(e) the VL FR2 set forth in SEQ ID NO: 28;(f) the VL FR3 set forth in SEQ ID NO: 192; and(g) the VL FR4 set forth in SEQ ID NO: 18; and(ii) the VH comprises:(B) the CDRH2 set forth in SEQ ID NO: 12;(C) the CDRH3 set forth in SEQ ID NO: 191;(D) the VH FR1 set forth in SEQ ID NO: 33;(E) the VH FR2 set forth in SEQ ID NO: 20;(F) the VH FR3 set forth in SEQ ID NO: 21 ; and(G) the VH FR4 set forth in SEQ ID NO: 22.24FH13167949.1BPX-05925

[0057] In some embodiments the VH and the VL comprise amino acid sequences having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequences selected from:(a) SEQ ID NOs: 35 and 40, respectively;(b) SEQ ID NOs: 35 and 49, respectively;(c) SEQ ID NOs: 35 and 50, respectively;(d) SEQ ID NOs: 35 and 41, respectively;(e) SEQ ID NOs: 35 and 46, respectively;(f) SEQ ID NOs: 36 and 50, respectively;(g) SEQ ID NOs: 36 and 40, respectively;(h) SEQ ID NOs: 36 and 41, respectively;(i) SEQ ID NOs: 36 and 42, respectively;(j) SEQ ID NOs: 36 and 43, respectively;(k) SEQ ID NOs: 36 and 44, respectively;(l) SEQ ID NOs: 37 and 50, respectively;(m) SEQ ID NOs: 37 and 40, respectively;(n) SEQ ID NOs: 37 and 46, respectively;(o) SEQ ID NOs: 37 and 48, respectively;(p) SEQ ID NOs: 38 and 50, respectively;(q) SEQ ID NOs: 38 and 51, respectively;(r) SEQ ID NOs: 38 and 52, respectively;(s) SEQ ID NOs: 38 and 40, respectively;(t) SEQ ID NOs: 38 and 41, respectively;(u) SEQ ID NOs: 38 and 45, respectively;(v) SEQ ID NOs: 38 and 46, respectively;(w) SEQ ID NOs: 38 and 47, respectively;(x) SEQ ID NOs: 38 and 48, respectively;(y) SEQ ID NOs: 39 and 40, respectively;(z) SEQ ID NOs: 38 and 195, respectively;(aa) SEQ ID NOs: 38 and 196, respectively;(bb) SEQ ID NOs: 38 and 197, respectively;25FH13167949.1BPX-05925(cc) SEQ ID NOs: 194 and 41, respectively;(dd) SEQ ID NOs: 194 and 195, respectively;(ee) SEQ ID NOs: 38 and 198, respectively;(ff) SEQ ID NOs: 38 and 199, respectively;(gg) SEQ ID NOs: 194 and 197, respectively;(hh) SEQ ID NOs: 38 and 200, respectively;(ii) SEQ ID NOs: 38 and 201, respectively;(jj) SEQ ID NOs: 194 and 200, respectively;(kk) SEQ ID NOs: 38 and 202, respectively;(11) SEQ ID NOs: 38 and 203, respectively; and(mm) SEQ ID NOs: 194 and 202, respectively.

[0058] In some embodiments the VH and the VL comprise amino acid sequences having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequences selected from:(a) SEQ ID NOs: 35 and 40, respectively;(b) SEQ ID NOs: 35 and 49, respectively;(c) SEQ ID NOs: 35 and 50, respectively;(d) SEQ ID NOs: 35 and 41, respectively;(e) SEQ ID NOs: 35 and 46, respectively;(f) SEQ ID NOs: 36 and 50, respectively;(g) SEQ ID NOs: 36 and 40, respectively;(h) SEQ ID NOs: 36 and 41, respectively;(i) SEQ ID NOs: 36 and 42, respectively;(j) SEQ ID NOs: 36 and 43, respectively;(k) SEQ ID NOs: 36 and 44, respectively;(l) SEQ ID NOs: 37 and 50, respectively;(m) SEQ ID NOs: 37 and 40, respectively;(n) SEQ ID NOs: 37 and 46, respectively;(o) SEQ ID NOs: 37 and 48, respectively;(p) SEQ ID NOs: 38 and 50, respectively;(q) SEQ ID NOs: 38 and 51, respectively;26FH13167949.1BPX-05925(r) SEQ ID NOs: 38 and 52, respectively;(s) SEQ ID NOs: 38 and 40, respectively;(t) SEQ ID NOs: 38 and 41, respectively;(u) SEQ ID NOs: 38 and 45, respectively;(v) SEQ ID NOs: 38 and 46, respectively;(w) SEQ ID NOs: 38 and 47, respectively;(x) SEQ ID NOs: 38 and 48, respectively; and(y) SEQ ID NOs: 39 and 40, respectively.

[0059] In some embodiments the VH and the VL comprise the amino acid sequences selected from:(a) SEQ ID NOs: 35 and 40, respectively;(b) SEQ ID NOs: 35 and 49, respectively;(c) SEQ ID NOs: 35 and 50, respectively;(d) SEQ ID NOs: 35 and 41, respectively;(e) SEQ ID NOs: 35 and 46, respectively;(f) SEQ ID NOs: 36 and 50, respectively;(g) SEQ ID NOs: 36 and 40, respectively;(h) SEQ ID NOs: 36 and 41, respectively;(i) SEQ ID NOs: 36 and 42, respectively;(j) SEQ ID NOs: 36 and 43, respectively;(k) SEQ ID NOs: 36 and 44, respectively;(l) SEQ ID NOs: 37 and 50, respectively;(m) SEQ ID NOs: 37 and 40, respectively;(n) SEQ ID NOs: 37 and 46, respectively;(o) SEQ ID NOs: 37 and 48, respectively;(p) SEQ ID NOs: 38 and 50, respectively;(q) SEQ ID NOs: 38 and 51, respectively;(r) SEQ ID NOs: 38 and 52, respectively;(s) SEQ ID NOs: 38 and 40, respectively;(t) SEQ ID NOs: 38 and 41, respectively;(u) SEQ ID NOs: 38 and 45, respectively;27FH13167949.1BPX-05925(v) SEQ ID NOs: 38 and 46, respectively;(w) SEQ ID NOs: 38 and 47, respectively;(x) SEQ ID NOs: 38 and 48, respectively;(y) SEQ ID NOs: 39 and 40, respectively(z) SEQ ID NOs: 38 and 195, respectively;(aa) SEQ ID NOs: 38 and 196, respectively;(bb) SEQ ID NOs: 38 and 197, respectively;(cc) SEQ ID NOs: 194 and 41, respectively;(dd) SEQ ID NOs: 194 and 195, respectively;(ee) SEQ ID NOs: 38 and 198, respectively;(ff) SEQ ID NOs: 38 and 199, respectively;(gg) SEQ ID NOs: 194 and 197, respectively;(hh) SEQ ID NOs: 38 and 200, respectively;(ii) SEQ ID NOs: 38 and 201, respectively;(jj) SEQ ID NOs: 194 and 200, respectively;(kk) SEQ ID NOs: 38 and 202, respectively;(11) SEQ ID NOs: 38 and 203, respectively; and(mm) SEQ ID NOs: 194 and 202, respectively.

[0060] In some embodiments the VH and the VL comprise the amino acid sequences selected from:(a) SEQ ID NOs: 35 and 40, respectively;(b) SEQ ID NOs: 35 and 49, respectively;(c) SEQ ID NOs: 35 and 50, respectively;(d) SEQ ID NOs: 35 and 41, respectively;(e) SEQ ID NOs: 35 and 46, respectively;(f) SEQ ID NOs: 36 and 50, respectively;(g) SEQ ID NOs: 36 and 40, respectively;(h) SEQ ID NOs: 36 and 41, respectively;(i) SEQ ID NOs: 36 and 42, respectively;(j) SEQ ID NOs: 36 and 43, respectively;(k) SEQ ID NOs: 36 and 44, respectively;28FH13167949.1BPX-05925(l) SEQ ID NOs: 37 and 50, respectively;(m) SEQ ID NOs: 37 and 40, respectively;(n) SEQ ID NOs: 37 and 46, respectively;(o) SEQ ID NOs: 37 and 48, respectively;(p) SEQ ID NOs: 38 and 50, respectively;(q) SEQ ID NOs: 38 and 51, respectively;(r) SEQ ID NOs: 38 and 52, respectively;(s) SEQ ID NOs: 38 and 40, respectively;(t) SEQ ID NOs: 38 and 41, respectively;(u) SEQ ID NOs: 38 and 45, respectively;(v) SEQ ID NOs: 38 and 46, respectively;(w) SEQ ID NOs: 38 and 47, respectively;(x) SEQ ID NOs: 38 and 48, respectively; and(y) SEQ ID NOs: 39 and 40, respectively.

[0061] In some embodiments, the antibody or antigen binding fragment described herein comprises a heavy chain constant region. In some embodiments, the heavy chain constant region is an IgG constant region. In some embodiments, the IgG constant region is a wild-type IgG constant region. In some embodiments, the IgG constant region comprises at least one mutation relative to a wild-type IgG constant region. In some embodiments, the IgG constant region is an IgGl, IgG2, IgG3, or IgG4 constant region. In some embodiments, the IgG constant region is an IgGl constant region. In some embodiments, the IgGl constant region is a wild-type human IgGl constant region. In some embodiments, the IgGl constant region comprises at least one amino acid substitution relative to a wild-type human IgGl constant region. In some embodiments, the IgGl constant region comprises at least one amino acid substitution selected from: L234A, L235A, L235E, H268Q, V309L, A330S, P331S, and any combination thereof, relative to a wild-type human IgGl constant region, according to EU numbering. In some embodiments, the IgGl constant region comprises at least one amino acid substitution selected from: M252Y, S264T, T256E, M428L, N434S, and any combination thereof, relative to a wild-type human IgGl constant region, according to EU numbering. In some embodiments, the IgGl constant region comprises an N297A, N297Q or N297G amino acid substitution relative to a wild-type human IgGl constant region, according to EU numbering. In some embodiments, the IgGl constant region comprises an amino acid sequence29FH13167949.1BPX-05925 having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to an amino acid sequence selected from SEQ ID Nos: 171-176. In some embodiments, the IgG2 constant region is a wild-type human IgG2 constant region. In some embodiments, the IgG2 constant region comprises at least one amino acid substitution selected from: H268Q, V309L, A330S, P331S, V234A, G237A, P238S, H268A, and any combination thereof, relative to a wild-type human IgG2 constant region, according to EU numbering. In some embodiments, the IgG2 constant region comprises an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to the amino acid sequence of SEQ ID NO: 177. In some embodiments, the IgG3 constant region is a wild-type human IgG3 constant region. In some embodiments, the IgG3 constant region comprises an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to the amino acid sequence of SEQ ID NO: 178. In some embodiments, the IgG4 constant region is a wild-type human IgG4 constant region. In some embodiments, the IgG4 constant region comprises an F234A and / or an L235A amino acid substitution relative to a wild-type human IgG4 constant region, according to EU numbering. In some embodiments, the IgG4 constant region comprises an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to the ammo acid sequence of SEQ ID NO: 179.

[0062] In some embodiments, the antibody or antigen binding fragment described herein comprises a light chain constant region. In some embodiments, the light chain constant region is a kappa light chain or a lambda light chain. In some embodiments, the kappa light chain comprises an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to the amino acid sequence of SEQ ID NO: 180. In some embodiments, the lambda light chain comprises an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to the amino acid sequence of SEQ ID NO: 181.

[0063] In some embodiments, the antibody or antigen binding fragment described herein comprises a heavy chain sequence and a light chain sequence comprising amino acid sequences having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequences selected from:(a) SEQ ID NOs: 53 and 58, respectively;(b) SEQ ID NOs: 53 and 70, respectively;(c) SEQ ID NOs: 53 and 67, respectively;30FH13167949.1BPX-05925(d) SEQ ID NOs: 53 and 66, respectively;(e) SEQ ID NOs: 53 and 63, respectively;(f) SEQ ID NOs: 54 and 58, respectively;(g) SEQ ID NOs: 54 and 66, respectively;(h) SEQ ID NOs: 54 and 59, respectively;(i) SEQ ID NOs: 54 and 60, respectively;(j) SEQ ID NOs: 54 and 61, respectively;(k) SEQ ID NOs: 54 and 67, respectively;(l) SEQ ID NOs: 55 and 58, respectively;(m) SEQ ID NOs: 55 and 63, respectively;(n) SEQ ID NOs: 55 and 65, respectively;(o) SEQ ID NOs: 55 and 67, respectively;(p) SEQ ID NOs: 56 and 67, respectively;(q) SEQ ID NOs: 56 and 68, respectively;(r) SEQ ID NOs: 56 and 69, respectively;(s) SEQ ID NOs: 56 and 58, respectively;(t) SEQ ID NOs: 56 and 66, respectively;(u) SEQ ID NOs: 56 and 62, respectively;(v) SEQ ID NOs: 56 and 63, respectively;(w) SEQ ID NOs: 56 and 64, respectively;(x) SEQ ID NOs: 56 and 65, respectively;(y) SEQ ID NOs: 57 and 58, respectively;(z) SEQ ID NOs: 56 and 205, respectively;(aa) SEQ ID NOs: 56 and 206, respectively;(bb) SEQ ID NOs: 56 and 207, respectively;(cc) SEQ ID NOs: 204 and 66, respectively;(dd) SEQ ID NOs: 204 and 205, respectively;(ee) SEQ ID NOs: 56 and 208, respectively;(ff) SEQ ID NOs: 56 and 209, respectively;(gg) SEQ ID NOs: 204 and 207, respectively;(hh) SEQ ID NOs: 56 and 210, respectively;31FH13167949.1BPX-05925(ii) SEQ ID NOs: 56 and 211, respectively;(jj) SEQ ID NOs: 204 and 210, respectively;(kk) SEQ ID NOs: 56 and 212, respectively;(11) SEQ ID NOs: 56 and 213, respectively; and(mm) SEQ ID NOs: 204 and 212, respectively.

[0064] In some embodiments, the antibody or antigen binding fragment described herein comprises a heavy chain sequence and a light chain sequence comprising amino acid sequences having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequences selected from:(a) SEQ ID NOs: 53 and 58, respectively;(b) SEQ ID NOs: 53 and 70, respectively;(c) SEQ ID NOs: 53 and 67, respectively;(d) SEQ ID NOs: 53 and 66, respectively;(e) SEQ ID NOs: 53 and 63, respectively;(f) SEQ ID NOs: 54 and 58, respectively;(g) SEQ ID NOs: 54 and 66, respectively;(h) SEQ ID NOs: 54 and 59, respectively;(i) SEQ ID NOs: 54 and 60, respectively;(j) SEQ ID NOs: 54 and 61, respectively;(k) SEQ ID NOs: 54 and 67, respectively;(l) SEQ ID NOs: 55 and 58, respectively;(m) SEQ ID NOs: 55 and 63, respectively;(n) SEQ ID NOs: 55 and 65, respectively;(o) SEQ ID NOs: 55 and 67, respectively;(p) SEQ ID NOs: 56 and 67, respectively;(q) SEQ ID NOs: 56 and 68, respectively;(r) SEQ ID NOs: 56 and 69, respectively;(s) SEQ ID NOs: 56 and 58, respectively;(t) SEQ ID NOs: 56 and 66, respectively;(u) SEQ ID NOs: 56 and 62, respectively;(v) SEQ ID NOs: 56 and 63, respectively;32FH13167949.1BPX-05925(w) SEQ ID NOs: 56 and 64, respectively;(x) SEQ ID NOs: 56 and 65, respectively; and(y) SEQ ID NOs: 57 and 58, respectively.

[0065] In some embodiments, the antibody or antigen binding fragment described herein comprises a heavy chain sequence and a light chain sequence comprising the amino acid sequences selected from:(a) SEQ ID NOs: 53 and 58, respectively;(b) SEQ ID NOs: 53 and 70, respectively;(c) SEQ ID NOs: 53 and 67, respectively;(d) SEQ ID NOs: 53 and 66, respectively;(e) SEQ ID NOs: 53 and 63, respectively;(f) SEQ ID NOs: 54 and 58, respectively;(g) SEQ ID NOs: 54 and 66, respectively;(h) SEQ ID NOs: 54 and 59, respectively;(i) SEQ ID NOs: 54 and 60, respectively;(j) SEQ ID NOs: 54 and 61, respectively;(k) SEQ ID NOs: 54 and 67, respectively;(l) SEQ ID NOs: 55 and 58, respectively;(m) SEQ ID NOs: 55 and 63, respectively;(n) SEQ ID NOs: 55 and 65, respectively;(o) SEQ ID NOs: 55 and 67, respectively;(p) SEQ ID NOs: 56 and 67, respectively;(q) SEQ ID NOs: 56 and 68, respectively;(r) SEQ ID NOs: 56 and 69, respectively;(s) SEQ ID NOs: 56 and 58, respectively;(t) SEQ ID NOs: 56 and 66, respectively;(u) SEQ ID NOs: 56 and 62, respectively;(v) SEQ ID NOs: 56 and 63, respectively;(w) SEQ ID NOs: 56 and 64, respectively;(x) SEQ ID NOs: 56 and 65, respectively;(y) SEQ ID NOs: 57 and 58, respectively33FH13167949.1BPX-05925(z) SEQ ID NOs: 56 and 205, respectively;(aa) SEQ ID NOs: 56 and 206, respectively;(bb) SEQ ID NOs: 56 and 207, respectively;(cc) SEQ ID NOs: 204 and 66, respectively;(dd) SEQ ID NOs: 204 and 205, respectively;(ee) SEQ ID NOs: 56 and 208, respectively;(ff) SEQ ID NOs: 56 and 209, respectively;(gg) SEQ ID NOs: 204 and 207, respectively;(hh) SEQ ID NOs: 56 and 210, respectively;(ii) SEQ ID NOs: 56 and 211, respectively;(jj) SEQ ID NOs: 204 and 210, respectively;(kk) SEQ ID NOs: 56 and 212, respectively;(11) SEQ ID NOs: 56 and 213, respectively; and(mm) SEQ ID NOs: 204 and 212, respectively.

[0066] In some embodiments, the antibody or antigen binding fragment described herein comprises a heavy chain sequence and a light chain sequence comprising the amino acid sequences selected from:(a) SEQ ID NOs: 53 and 58, respectively;(b) SEQ ID NOs: 53 and 70, respectively;(c) SEQ ID NOs: 53 and 67, respectively;(d) SEQ ID NOs: 53 and 66, respectively;(e) SEQ ID NOs: 53 and 63, respectively;(f) SEQ ID NOs: 54 and 58, respectively;(g) SEQ ID NOs: 54 and 66, respectively;(h) SEQ ID NOs: 54 and 59, respectively;(i) SEQ ID NOs: 54 and 60, respectively;(j) SEQ ID NOs: 54 and 61, respectively;(k) SEQ ID NOs: 54 and 67, respectively;(l) SEQ ID NOs: 55 and 58, respectively;(m) SEQ ID NOs: 55 and 63, respectively;(n) SEQ ID NOs: 55 and 65, respectively;34FH13167949.1BPX-05925(o) SEQ ID NOs: 55 and 67, respectively;(p) SEQ ID NOs: 56 and 67, respectively;(q) SEQ ID NOs: 56 and 68, respectively;(r) SEQ ID NOs: 56 and 69, respectively;(s) SEQ ID NOs: 56 and 58, respectively;(t) SEQ ID NOs: 56 and 66, respectively;(u) SEQ ID NOs: 56 and 62, respectively;(v) SEQ ID NOs: 56 and 63, respectively;(w) SEQ ID NOs: 56 and 64, respectively;(x) SEQ ID NOs: 56 and 65, respectively; and(y) SEQ ID NOs: 57 and 58, respectively.

[0067] In some aspects, the disclosure provides a conjugate comprising (i) an antibody or antigen binding fragment described herein, and (ii) at least one regulator of complement activation (RCA) polypeptide.

[0068] In further aspects, the disclosure provides a conjugate comprising (i) an antibody, or antigen binding fragment thereof, that specifically binds C2, and (ii) at least one RCA polypeptide.

[0069] In other aspects, the disclosure provides a conjugate comprising (i) a means for binding C2, and (ii) at least one RCA polypeptide.

[0070] In some embodiments, the RCA polypeptide of the conjugate comprises an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to an amino acid sequence selected from SEQ ID Nos: 89-104. In some embodiments, the RCA polypeptide comprises an amino acid sequence selected from SEQ ID Nos: 89-104.

[0071] In some embodiments, the antibody or antigen binding fragment, or the means for binding C2, is conjugated to the at least one RCA polypeptide via a linker. In some embodiments, the linker is a peptide linker. In some embodiments, the peptide linker is a GlySer linker. In some embodiments, the GlySer linker is a (GxSy)zlinker, wherein x is 3-6, y is 0 or 1, and z is 1-5. In some embodiments, the GlySer linker is a (GGGGS), (GGGGS)(GGGGS) or (GGGGS)(GGGGS)(GGGGS) linker. In some embodiments, the GlySer linker is a (GGGGS)n(PGGGS)xlinker, wherein P is proline, a (GGGPS)n(GGGGS)xlinker, wherein P is proline, a (GGGGA)n(GGGGS)xlinker, where A is alanine, or a (GGGGQ)n(GGGGS)xlinker, wherein Q is glutamine, where for each linker n is 1-3, and x is 0 or 1, optionally wherein n is 1 or35FH13167949.1BPX-059252. In some embodiments, the peptide linker comprises an amino acid sequence selected from SEQ ID Nos: 105-168.

[0072] In some embodiments, the conjugate comprises two or more RCA polypeptide. In some embodiments, the two or more RCA polypeptides are the same. In some embodiments, the two or more RCA polypeptides are different. In some embodiments, the two or more RCA polypeptides are linked to each other via a linker. In some embodiments, the linker is a peptide In some embodiments, the peptide linker is a GlySer linker. In some embodiments, the GlySer linker is a (GxSy)z linker, wherein x is 3-6, y is 0 or 1, and z is 1-5. In some embodiments, the GlySer linker is a (GGGGS), (GGGGSj(GGGGS) or (GGGGS)(GGGGS)(GGGGS) linker. In some embodiments, the GlySer linker is a (GGGGS)n(PGGGS)xlinker, wherein P is proline, a (GGGPS)n(GGGGS)xlinker, wherein P is proline, a (GGGGA)n(GGGGS)xlinker, where A is alanine, or a (GGGGQ)n(GGGGS)xlinker, wherein Q is glutamine, where for each linker n is 1-3, and x is 0 or 1, optionally wherein n is 1 or 2. In some embodiments, the peptide linker comprises an amino acid sequence selected from SEQ ID Nos: 105-168. In some embodiments, the two or more RCA polypeptides independently comprise SEQ ID Nos: 89 and 93.

[0073] In some embodiments, the at least one RCA polypeptide is conjugated to a heavy chain of the antibody or the means for binding C2.

[0074] In some embodiments, the at least one RCA polypeptide is conjugated to a light chain of the antibody or the means for binding C2.

[0075] In some aspects, the disclosure provides a conjugate comprising the formula of: ANTIBOD Y-(LINKER1 xi -RCA1 )n-LINKER2X2-RCA2, wherein “ANTIBODY” is an antibody or antigen binding fragment described herein; wherein “LINKER1” and “LINKER2” are each independently a peptide linker; wherein “RCA1” and “RCA2” are each independently an RCA polypeptide; and wherein "n" is 0-5, XI is independently 0 or 1 and X2 is 0 or 1.

[0076] In some embodiments, RCA1 and RCA2 are each independently selected from SEQ ID Nos: 89-104. In some embodiments, RCA1 and RCA2 are each independently selected from SEQ ID Nos: 89, 93, or 97, and “n” is 1 and XI and X2 are each 1 or wherein RCA2 is SEQ ID Nos: 89, 93, or 97, and “n” is 0 and X2 is 1. In some embodiments, LINKER1 and LINKER2 are each a GlySer linker. In some embodiments, LINKER1 and LINKER2 are each independently a (GxSy)z linker, wherein x is 3-6, y is 0 or 1, and z is 1-5. In some embodiments, LINKER1 and36FH13167949.1BPX-05925LINKER2 are each independently a (GGGGS), (GGGGS)(GGGGS) or(GGGGS) (GGGGS) (GGGGS) linker. In some embodiments, LINKER! and LINKER2 are each independently a (GGGGS)n(PGGGS)xlinker, wherein P is proline, a (GGGGS)n(PGGGS)xlinker where P is proline, a (GGGPS)n(GGGGS)xlinker, wherein P is proline, a (GGGGA)n(GGGGS)xlinker, where A is alanine, or a (GGGGQ)n(GGGGS)xlinker, wherein Q is glutamine, where for each linker n is 1-3, and x is 0 or 1, optionally wherein n is 1 or 2. In some embodiments, LINKER1 and LINKER2 are each independently selected from SEQ ID Nos: 105-168.

[0077] In some aspects, the disclosure provides a conjugate comprising a heavy chain comprising an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to an amino acid sequence selected from SEQ ID Nos: 71-88 and a light chain comprising an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to an amino acid sequence selected from SEQ ID Nos: 58-70.

[0078] In other aspects, the disclosure provides a conjugate comprising a heavy chain comprising an amino acid sequence selected from SEQ ID Nos: 71-88, and a light chain comprising an amino acid sequence selected from SEQ ID Nos: 58-70.

[0079] In further aspects, the disclosure provides a conjugate comprising a heavy chain and a light chain comprising amino acid sequences having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequences selected from:(a) SEQ ID NOs: 71 and 67, respectively;(b) SEQ ID NOs: 71 and 58, respectively;(c) SEQ ID NOs: 72 and 58, respectively;(d) SEQ ID NOs: 72 and 67, respectively;(e) SEQ ID NOs: 72 and 66, respectively;(f) SEQ ID NOs: 73 and 68, respectively;(g) SEQ ID NOs: 73 and 62, respectively;(h) SEQ ID NOs: 73 and 64, respectively;(i) SEQ ID NOs: 73 and 63, respectively;(j) SEQ ID NOs: 73 and 65, respectively;(k) SEQ ID NOs: 73 and 66, respectively;(l) SEQ ID NOs: 74 and 58, respectively;(m) SEQ ID NOs: 75 and 58, respectively;37FH13167949.1BPX-05925(n) SEQ ID NOs: 76 and 58, respectively;(o) SEQ ID NOs: 76 and 63, respectively;(p) SEQ ID NOs: 77 and 58, respectively;(q) SEQ ID NOs: 77 and 63, respectively;(r) SEQ ID NOs: 78 and 58, respectively;(s) SEQ ID NOs: 78 and 63, respectively;(t) SEQ ID NOs: 79 and 63, respectively;(u) SEQ ID NOs: 79 and 65, respectively;(v) SEQ ID NOs: 80 and 63, respectively;(w) SEQ ID NOs: 80 and 65, respectively;(x) SEQ ID NOs: 81 and 63, respectively;(y) SEQ ID NOs: 81 and 65, respectively;(z) SEQ ID NOs: 82 and 63, respectively;(aa) SEQ ID NOs: 83 and 63, respectively;(bb) SEQ ID NOs: 83 and 66, respectively;(cc) SEQ ID NOs: 84 and 63, respectively;(dd) SEQ ID NOs: 85 and 58, respectively;(ee) SEQ ID NOs: 86 and 63, respectively;(ff) SEQ ID NOs: 86 and 66, respectively;(gg) SEQ ID NOs: 86 and 65, respectively;(hh) SEQ ID NOs: 87 and 58, respectively;(ii) SEQ ID NOs: 88 and 63, respectively;(jj) SEQ ID NOs: 88 and 66, respectively; and(kk) SEQ ID NOs: 88 and 65, respectively.

[0080] In yet further aspects, the disclosure provides a conjugate comprising a heavy chain and a light chain comprising the amino acid sequences selected from:(a) SEQ ID NOs: 71 and 67, respectively;(b) SEQ ID NOs: 71 and 58, respectively;(c) SEQ ID NOs: 72 and 58, respectively;(d) SEQ ID NOs: 72 and 67, respectively;(e) SEQ ID NOs: 72 and 66, respectively;38FH13167949.1BPX-05925(f) SEQ ID NOs: 73 and 68, respectively;(g) SEQ ID NOs: 73 and 62, respectively;(h) SEQ ID NOs: 73 and 64, respectively;(i) SEQ ID NOs: 73 and 63, respectively;(j) SEQ ID NOs: 73 and 65, respectively;(k) SEQ ID NOs: 73 and 66, respectively;(l) SEQ ID NOs: 74 and 58, respectively;(m) SEQ ID NOs: 75 and 58, respectively;(n) SEQ ID NOs: 76 and 58, respectively;(o) SEQ ID NOs: 76 and 63, respectively;(p) SEQ ID NOs: 77 and 58, respectively;(q) SEQ ID NOs: 77 and 63, respectively;(r) SEQ ID NOs: 78 and 58, respectively;(s) SEQ ID NOs: 78 and 63, respectively;(t) SEQ ID NOs: 79 and 63, respectively;(u) SEQ ID NOs: 79 and 65, respectively;(v) SEQ ID NOs: 80 and 63, respectively;(w) SEQ ID NOs: 80 and 65, respectively;(x) SEQ ID NOs: 81 and 63, respectively;(y) SEQ ID NOs: 81 and 65, respectively;(z) SEQ ID NOs: 82 and 63, respectively;(aa) SEQ ID NOs: 83 and 63, respectively;(bb) SEQ ID NOs: 83 and 66, respectively;(cc) SEQ ID NOs: 84 and 63, respectively;(dd) SEQ ID NOs: 85 and 58, respectively;(ee) SEQ ID NOs: 86 and 63, respectively;(ff) SEQ ID NOs: 86 and 66, respectively;(gg) SEQ ID NOs: 86 and 65, respectively;(hh) SEQ ID NOs: 87 and 58, respectively;(ii) SEQ ID NOs: 88 and 63, respectively;(jj) SEQ ID NOs: 88 and 66, respectively; and39FH13167949.1BPX-05925(kk) SEQ ID NOs: 88 and 65, respectively.

[0081] In some aspects, the disclosure provides a composition comprising an antibody or antigen binding fragment disclosed herein. In other aspects, the disclosure provides a composition comprising a conjugate described herein. In some embodiments, the composition comprises a pharmaceutically acceptable carrier.

[0082] In some aspects, the disclosure provides a nucleic acid comprising a nucleotide sequence encoding the VL, the VH, the heavy chain, the light chain, or any combination thereof, of an antibody or antigen binding fragment described herein. In other aspects, the disclosure provides a nucleic acid comprising a nucleotide sequence encoding a conjugate described herein. In further aspects, the disclosure provides an expression vector comprising a nucleic acid described herein. In some aspects, the disclosure provides a cell comprising an expression vector described herein. In other aspects, the disclosure provides a method for producing an antibody or antigen binding fragment or a conjugate described herein, the method comprising maintaining a cell described herein under conditions permitting expression of the antibody or antigen binding fragment, or the conjugate.

[0083] In some aspects, the disclosure provides a method for treating a complement- associated disease or disorder in a subject, comprising administering to the subject an antibody or antigen binding fragment, a conjugate, or a composition described herein. In some embodiments, the complement-associated disease or disorder is selected from amyotrophic lateral sclerosis (ALS), antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis, atypical hemolytic uremic syndrome (aHUS), aHUS after kidney transplant, autoimmune encephalitis, bullous pemphigoid, C3 glomerulopathy (C3G), C3 glomerulonephritis (C3GN), C3G relapse after kidney transplant, cold agglutinin disease (CAD), CD59 deficiency, CD59-mediated hemolytic anemia with or without immune-mediated polyneuropathy, CHAPLE syndrome (CD 55 deficiency), chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), complement Factor I deficiency, diabetic nephropathy, cryoglobulinemia, dense deposit disease, diabetic lumbosacral plexopathy, age-related macular degeneration (AMD), glaucoma, dry AMD, wet AMD, diabetic retinopathy, inherited retinal disease, retinal detachment, familial amyloid polyneuropathy, fibrillary glomerulonephritis, focal segmental glomerulosclerosis (FSGS), geographic atrophy, Goodpasture’s syndrome, Guillain-Barre syndrome, hematopoietic stem cell transplant-associated-thrombotic microangiopathy (HSCT-TMA), hidradenitis suppurativa, Huntington's disease, IgA nephropathy40FH13167949.1BPX-05925(IgAN), IGAN relapse after kidney transplant antibody mediated rejection (i.e., kidney transplant) post-transplant rejection (solid organ antibody mediated rejection), immune complex membranoproliferative glomerulonephritis (IC-MPGN), immune-mediated necrotizing myopathy, immunoglobulin A-associated vasculitis (IgAV), immunoglobulin A-associated vasculitis (IgAV) nephritis, immune thrombocytopenia (ITP), immune thrombocytopenic purpura, lupus nephritis, lupus nephritis flares with high urinary Ba or sCb5 -9, multiple sclerosis, multifocal motor neuropathy (MMN), myasthenia gravis, neuromyelitis optica spectrum disorder (NMOSD), paroxysmal nocturnal hemoglobinuria (PNH), post-infectious glomerulonephritis, primary membranous nephropathy (PMN), rhabdomyolysis-induced acute kidney injury (RIAKI), sickle cell disease, Sjogren's syndrome, tauopathy, thrombotic microangiopathy (TMA), systemic lupus erythematosus, thrombotic thrombocytopenic purpura (TTP), warm autoimmune hemolytic anemia (WAHA), acute spinal cord injuries, anti-MAG (myelin-associated glycoprotein) peripheral polyneuropathy (IgM neuropathy), pyoderma gangrenosum, dermatomyositis, hypocomplementemic urticarial vasculitis syndrome (HUVS), auto-immune chronic spontaneous urticaria (aiCUS), Kawasaki disease, Takayasu's arteritis, antiphospholipid therapy - thrombosis prevention (antiphospholipid syndrome), catastrophic antiphospholipid syndrome (CAPS), preeclampsia, HELLP syndrome, and autoimmune hepatitis (AIH). In some embodiments, the complement-associated disease or disorder is selected from cold agglutinin disease (CAD), atypical hemolytic uremic syndrome (aHUS), IgA nephropathy (IgAN), lupus nephritis (LN). In some embodiments, the complement-associated disease or disorder is selected from acute spinal cord injuries, CIDP, NMOSD, GBS, MMN, and IgM neuropathy. In some embodiments, the complement-associated disease or disorder is selected from delayed graft function (i.e., kidney transplant), Goodpasture's Syndrome, and C3G. In some embodiments, the complement-associated disease or disorder is selected from hidradenitis suppurativa, bullous pemphigoid, IgA Vasculitis, pyoderma gangrenosum, and dermatomyositis. In some embodiments, the complement-associated disease or disorder is selected from myasthenia gravis, Behcet's disease, IgG4-related disease, HSCT-TMA, IMNM, HUVS, aiCSU, Kawasaki disease, and Takayasu's arteritis. In some embodiments, the complement-associated disease or disorder is selected from antiphospholipid syndrome, CAD, CAPS, wAIHA, WAHA, post-transplant rejection (solid organ antibody mediated rejection), and antibody mediated rejection (i.e., kidney transplant). In some embodiments, the complement-associated disease or disorder is selected from dermatomyositis or MMN. In some41FH13167949.1BPX-05925 embodiments, the complement-associated disease or disorder is selected from bullous pemphigoid or HUVS.

[0084] In some aspects, the disclosure provides a kit comprising a container comprising an antibody or antigen binding fragment or a conjugate described herein, and an optional pharmaceutically acceptable carrier, and a package insert comprising instructions for administration of the antibody or antigen binding fragment, or the conjugate, to a subject in need thereof. In some embodiments, the subject has a complement-associated disease or disorder.

[0085] In some aspects, the disclosure provides the use of an antibody or antigen binding fragment, a conjugate, or a composition described herein, for the manufacture of a medicament for treating a complement-associated disease or disorder in a subject.

[0086] In some embodiments of the kit or use, wherein the complement-associated disease or disorder is selected from amyotrophic lateral sclerosis (ALS), antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis, atypical hemolytic uremic syndrome (aHUS), aHUS after kidney transplant, autoimmune encephalitis, bullous pemphigoid, C3 glomerulopathy (C3G), C3 glomerulonephritis (C3GN), C3G relapse after kidney transplant, cold agglutinin disease (CAD), CD59 deficiency, CD59-mediated hemolytic anemia with or without immune-mediated polyneuropathy, CHAPLE syndrome (CD55 deficiency), chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), complement Factor I deficiency, diabetic nephropathy, cryoglobulinemia, dense deposit disease, diabetic lumbosacral plexopathy, age-related macular degeneration (AMD), glaucoma, dry AMD, wet AMD, diabetic retinopathy, inherited retinal disease, retinal detachment, familial amyloid polyneuropathy, fibrillary glomerulonephritis, focal segmental glomerulosclerosis (FSGS), geographic atrophy, Goodpasture’s syndrome, Guillain- Barre syndrome, hematopoietic stem cell transplant-associated-thrombotic microangiopathy (HSCT-TMA), hidradenitis suppurativa, Huntington's disease, IgA nephropathy (IgAN), IGAN relapse after kidney transplant antibody mediated rejection (i.e., kidney transplant) post-transplant rejection (solid organ antibody mediated rejection), immune complex membranoproliferative glomerulonephritis (IC-MPGN), immune-mediated necrotizing myopathy, immunoglobulin A- associated vasculitis (IgAV), immunoglobulin A-associated vasculitis (IgAV) nephritis, immune thrombocytopenia (ITP), immune thrombocytopenic purpura, lupus nephritis, lupus nephritis flares with high urinary Ba or sCb5 -9, multiple sclerosis, multifocal motor neuropathy (MMN), myasthenia gravis, neuromyelitis optica spectrum disorder (NMOSD), paroxysmal nocturnal42FH13167949.1BPX-05925 hemoglobinuria (PNH), post-infectious glomerulonephritis, primary membranous nephropathy (PMN), rhabdomyolysis-induced acute kidney injury (RIAKI), sickle cell disease, Sjogren's syndrome, tauopathy, thrombotic microangiopathy (TMA), systemic lupus erythematosus, thrombotic thrombocytopenic purpura (TTP), warm autoimmune hemolytic anemia (WAHA), acute spinal cord injuries, anti-MAG (myelin-associated glycoprotein) peripheral polyneuropathy (IgM neuropathy), pyoderma gangrenosum, dermatomyositis, hypocomplementemic urticarial vasculitis syndrome (HUVS), auto-immune chronic spontaneous urticaria (aiCUS), Kawasaki disease, Takayasu's arteritis, antiphospholipid therapy - thrombosis prevention (antiphospholipid syndrome), catastrophic antiphospholipid syndrome (CAPS), pre-eclampsia, HELLP syndrome, and autoimmune hepatitis (AIH). In some embodiments, the complement-associated disease or disorder is selected from cold agglutinin disease (CAD), atypical hemolytic uremic syndrome (aHUS), IgA nephropathy (IgAN), lupus nephritis (LN). In some embodiments, the complement-associated disease or disorder is selected from acute spinal cord injuries, CIDP, NMOSD, GBS, MMN, and IgM neuropathy. In some embodiments, the complement-associated disease or disorder is selected from delayed graft function (i.e., kidney transplant), Goodpasture's Syndrome, and C3G. In some embodiments, the complement-associated disease or disorder is selected from hidradenitis suppurativa, bullous pemphigoid, IgA Vasculitis, pyoderma gangrenosum, and dermatomyositis. In some embodiments, the complement-associated disease or disorder is selected from myasthenia gravis, Behcet's disease, IgG4-related disease, HSCT-TMA, IMNM, HUVS, aiCSU, Kawasaki disease, and Takayasu's arteritis. In some embodiments, the complement-associated disease or disorder is selected from antiphospholipid syndrome, CAD, CAPS, wAIHA, WAHA, posttransplant rejection (solid organ antibody mediated rejection), and antibody mediated rejection (i.e., kidney transplant). In some embodiments, the complement-associated disease or disorder is selected from dermatomyositis or MMN. In some embodiments, the complement-associated disease or disorder is selected from bullous pemphigoid or HUVS.DETAILED DESCRIPTION

[0087] The present disclosure is based, at least in part, on the discovery of antibodies that bind C2, and conjugates of said antibodies with polypeptides of the regulator of complement activation (RCA) family.43FH13167949.1BPX-05925

[0088] Complement activation triggers a proteolytic cascade leading to the production of cleavage products with various biological functions. Complement can be activated by three different pathways, the classical, lecithin, and alternative pathways, each of which depend on different triggers for pathway initiation. All three complement activation pathways converge downstream, produce the same set of effector molecules and result in the generation of the C3 and C5 convertases. These convertases cleave C3 into the anaphylatoxin C3a and the opsin C3b and C5 into the anaphylatoxin C5a and C5b. The anaphylatoxins recruit and activate immune cells while the opsins promote phagocytic update of pathogens. C5b is responsible for initiating the formation of the membrane attack complex. The complement system can be activated by three initial pathways.

[0089] The classical pathway (CP) is typically activated when antibodies bind to an antigen, as well as in an antibody-independent manner by other substances (like C-reactive protein, serum amyloid P component, and pentraxin 3) when bound to the cell surface. On activation, Clq triggers the serine proteases Clr and Cis, which lead to the cleavage of C4 to C4b. This cleavage reaction exposes a specific binding site on C4b for C2. Cis then cleaves C2 to produce the C3 convertase (C4b2a). The C3 convertase is responsible for the cleavage of C3 into anaphylatoxin C3a and C3b, resulting in the ultimate formation of the C5 convertase (C4b2a3b). The C5 convertase catalyzes the last enzymatic step in the complement cascade, cleaving C5 into the anaphylatoxin C5a and C5b. C5b initiates the formation of the terminal C5b-9 membrane attack complex which, when inserted into a cell membrane, leads to cellular lysis.

[0090] The lectin pathway (LP) is initiated by mannose binding lectin (MBL), ficolins 1-3, and collectins, all of which recognize conserved structural patterns on microbes and damaged host cells. These molecules serve the same function as Clq in the CP and activate the MBL-associated serine proteases (MASPs). MASP-1 and MASP-2, which are involved in further activation of the complement pathway. Subsequent steps in the LP activation are virtually identical to CP activation.

[0091] The alternative pathway (AP) is activated differently than the CP and LP. While the AP can be activated specifically in response to lipopolysaccharides (LPS) and structures on the surface of host and foreign cells, the AP is constitutively active at low levels due to a process referred to as “tickover” of C3. This tickover produces a conformationally altered form of C3 referred to as C3(H2O). C3(H2O) can then bind Factor B, which can be cleaved into C3a and C3b by the constitutively active serine protease Factor D. C3b remains bound to C3(H2O) to form44FH13167949.1BPX-05925C3(H2O)Bb, which is capable of cleaving C3 into C3a and C3b. The produced C3b binds factor B, which is cleaved by factor D as above to form the second AP C3 convertase C3bBb, which is responsible for the amplification effects of the AP (regardless of which complement pathway is initiated). Properdin, the only positive regulator of complement activation, binds to C3bBb and stabilizes this complex (C3bBbP), which then cleaves C3 and binds to C3b to form the C5 convertase (C3b)2BbP that cleaves C5 in the same manner as the CP / LP C5 convertase. A major function of the alternative pathway is to amplify classical and lectin pathway activation from the C3 stage.

[0092] The terminal pathway proceeds in the same way irrespective of the initial pathway activation by assembly of the C5b6 complex and subsequent binding of C7 to form an amphiphilic complex that can insert into a lipid membrane. When C5b-7 is formed on a cell surface, one C8 and multiple C9 molecules are recruited leading to the formation of the membrane attack complex (MAC), which creates a physical pore that penetrates the membrane and leads to transmembrane leakage and subsequent cell or bacterial lysis.

[0093] While complement activation is necessary for the proper function of the immune system, overactivation and or inappropriate activation of the complement system has the potential to initiate immune and inflammatory diseases in the host. Dysregulation of the complement system has been shown to be a major contributing factor to a wide range of diseases, including asthma, glaucoma, vasculitis, hemolytic-uremic syndrome, and many others. While certain therapeutic options exist for the treatment of complement mediated disorders, the art is in need of new inhibitors of complement activation, particularly such inhibitors capable of inhibiting complement activation through multiple mechanisms, e.g., through one or more of the three pathways discussed above.

[0094] Certain terms are defined below. Additional definitions are set forth throughout the specification. The publications and other reference materials referenced herein are hereby incorporated by reference.

[0095] In this application, unless otherwise clear from context, (i) the terms “a” and “an” are used herein to refer to one or to more than one (i.e., to at least one) of the grammatical object of the article; (ii) the term “or” may be understood to mean “and / or”; (iii) the terms “comprising” and “including” may be understood to encompass itemized components or steps whether presented by45FH13167949.1BPX-05925 themselves or together with one or more additional components or steps; and (iv) where ranges are provided, endpoints are included unless explicitly excluded.

[0096] As used herein, “about” will be understood by persons of ordinary skill and will vary to some extent depending on the context in which it is used. If there are uses of the term which are unclear to persons of ordinary skill given the context in which it is used, "about" will mean up to plus or minus 10% of the particular value.

[0097] As used herein, the term “amino acid” refers to naturally occurring and synthetic amino acids, as well as amino acid analogs and amino acid mimetics that function in a manner similar to the naturally occurring amino acids. Naturally occurring amino acids are those encoded by the genetic code, as well as those amino acids that are later modified, e.g., hydroxyproline, y- carboxyglutamate, and O-phospho serine. Amino acid analogs refers to compounds that have the same basic chemical structure as a naturally occurring amino acid, i.e., a carbon that is bound to a hydrogen, a carboxyl group, an amino group, and an R group, e.g., homoserine, norleucine, methionine sulfoxide, methionine methyl sulfonium. Such analogs have modified R groups (e.g., norleucine) or modified peptide backbones, but retain the same basic chemical structure as a naturally occurring amino acid. Amino acid mimetics refers to chemical compounds that have a structure that is different from the general chemical structure of an amino acid, but that function in a manner similar to a naturally occurring amino acid.

[0098] Amino acids can be referred to herein by either their commonly known three letter symbols or by the one-letter symbols recommended by the IUPAC-IUB Biochemical Nomenclature Commission. Nucleotides, likewise, can be referred to by their commonly accepted single-letter codes.

[0099] As used herein, an “amino acid substitution” refers to the replacement of at least one existing amino acid residue in a predetermined amino acid sequence (an amino acid sequence of a starting polypeptide) with a second, different "replacement" amino acid residue. An “amino acid insertion” refers to the incorporation of at least one additional amino acid into a predetermined amino acid sequence. While the insertion will usually consist of the insertion of one or two amino acid residues, larger “peptide insertions,” can also be made, e.g, insertion of about three to about five or even up to about ten, fifteen, or twenty amino acid residues. The inserted residue(s) may be naturally occurring or non- naturally occurring as disclosed above. An "amino acid deletion" refers to the removal of at least one amino acid residue from a predetermined amino acid sequence.46FH13167949.1BPX-05925

[0100] As used herein, the term “antibody” refers to a whole antibody comprising two light chain polypeptides and two heavy chain polypeptides. Whole antibodies include different antibody isotypes including IgM, IgG, IgA, IgD, and IgE antibodies. The term “antibody” includes a polyclonal antibody, a monoclonal antibody, a chimerized or chimeric antibody, a humanized antibody, a primatized antibody, a deimmunized antibody, and a fully human antibody. The antibody can be a purified or a recombinant antibody.

[0101] As used herein, the terms “antibody fragment,” “antigen-binding fragment,” “antigen binding portion” or similar terms refer to a fragment of an antibody that retains the ability to bind to a target antigen (e.g., C2) and inhibit at least one activity of the target antigen. Such fragments include, e.g, a single chain antibody, a single chain Fv fragment (scFv), an Fd fragment, a Fab fragment, a Fab' fragment, or an F(ab')2 fragment. An scFv fragment is a single polypeptide chain that includes both the heavy and light chain variable regions of the antibody from which the scFv is derived. In addition, intrabodies, minibodies, triabodies, and diabodies are also included in the definition of antibody and are compatible for use in the methods described herein. See, e.g, Todorovska et al., (2001) J. Immunol. Methods 248(l):47-66; Hudson and Kortt, (1999) J. Immunol. Methods 231(1): 177-189; Poljak, (1994) Structure 2(12): 1121-1123; Rondon and Marasco, (1997) Annu. Rev. Microbiol. 51:257-283, the disclosures of each of which are incorporated herein by reference in their entirety. In some embodiments, the antibody fragment is a single light chain, a single heavy chain, and an Fc domain of a CH2 and a CH3 domain.

[0102] As used herein, the term “antibody fragment” also includes, e.g, single domain antibodies such as camelized single domain antibodies. See, e.g, Muyldermans et al., (2001) Trends Biochem. Sci. 26:230-235; Nuttall et al., (2000) Curr. Pharm. Biotech. 1:253-263; Reichmann et al., (1999) J. Immunol. Meth. 231:25-38; PCT application publication nos. WO 94 / 04678 and WO 94 / 25591; and U.S. patent no. 6,005,079, all of which are incorporated herein by reference in their entireties. In some embodiments, the disclosure provides single domain antibodies comprising two VH domains with modifications such that single domain antibodies are formed.

[0103] In some embodiment, an antigen-binding fragment includes the variable region of a heavy chain polypeptide and the variable region of a light chain polypeptide. In some embodiments, an antigen-binding fragment described herein comprises the CDRs of the light chain and heavy chain polypeptide of an antibody.47FH13167949.1BPX-05925

[0104] It will also be understood by one of ordinary skill in the art that the antibodies suitable for use in the methods disclosed herein may be altered such that they vary in sequence from the naturally occurring or native sequences from which they were derived, while retaining the desirable activity of the native sequences. For example, nucleotide or amino acid substitutions leading to conservative substitutions or changes at “non-essential” amino acid residues may be made. Mutations may be introduced by standard techniques, such as site-directed mutagenesis and PCR-mediated mutagenesis.

[0105] The antibodies suitable for use in the methods disclosed herein may comprise conservative amino acid substitutions at one or more amino acid residues, e.g., at essential or non- essential amino acid residues. A “conservative amino acid substitution” is one in which the amino acid residue is replaced with an amino acid residue having a similar side chain. Families of amino acid residues having similar side chains have been defined in the art, including basic side chains (e.g., lysine, arginine, histidine), acidic side chains (e.g., aspartic acid, glutamic acid), uncharged polar side chains (e.g., glycine, asparagine, glutamine, serine, threonine, tyrosine, cysteine), nonpolar side chains (e.g., alanine, valine, leucine, isoleucine, proline, phenylalanine, methionine, tryptophan), beta-branched side chains (e.g., threonine, valine, isoleucine) and aromatic side chains (e.g., tyrosine, phenylalanine, tryptophan, histidine). Thus, a nonessential amino acid residue in a binding polypeptide is preferably replaced with another amino acid residue from the same side chain family. In certain embodiments, a string of amino acids can be replaced with a structurally similar string that differs in order and / or composition of side chain family members. Alternatively, in certain embodiments, mutations may be introduced randomly along all or part of a coding sequence, such as by saturation mutagenesis, and the resultant mutants can be incorporated into binding polypeptides provided herein and screened for their ability to bind to the desired target.

[0106] As used herein, a subject “in need of prevention,” “in need of treatment,” or “in need thereof,” refers to one, who by the judgment of an appropriate medical practitioner (e.g., a doctor, a nurse, or a nurse practitioner in the case of humans; a veterinarian in the case of non-human mammals), would reasonably benefit from a given treatment (such as treatment with a composition comprising an anti-C2 antibody or an anti-C2 antibody conjugate described herein).

[0107] As used herein, the term “isolated antibody” is intended to refer to an antibody which is substantially free of other antibodies having different antigenic specificities (e.g., an isolated antibody that specifically binds to human C2 is substantially free of antibodies that specifically bind48FH13167949.1BPX-05925 antigens other than C2). An isolated antibody that specifically binds to an epitope may, however, have cross-reactivity to other C2 proteins from different species. However, the antibody continues to display specific binding to human C2 in a specific binding assay as described herein. In addition, an isolated antibody is typically substantially free of other cellular material and / or chemicals. In some embodiments, a combination of “isolated” antibodies having different C2 specificities is combined in a well-defined composition.

[0108] As used herein, the term “isolated nucleic acid molecule” refers to nucleic acids encoding antibodies, antibody portions (e.g., VH, VL, CDR3) that bind to C2, and / or an anti-C2 antibody conjugate described herein, and is intended to refer to a nucleic acid molecule in which the nucleotide sequences encoding the antibody, antibody portion, and / or antibody conjugate are free of other nucleotide sequences encoding antibodies, antibody portions, or antibody conjugates that bind antigens other than C2, which other sequences may naturally flank the nucleic acid in human genomic DNA.

[0109] As used herein, “isotype” refers to the antibody class (e.g., IgM or IgGl) that is encoded by heavy chain constant region genes. In some embodiments, an antibody of the disclosure is of the IgGl isotype. In some embodiments, an antibody of the disclosure is of the IgGl isotype and comprises a mutation. In some embodiments, an antibody of the disclosure is of the IgG2 isotype. In some embodiments, an antibody of the disclosure is of the IgG3 isotype. In some embodiments, an antibody of the disclosure is of the IgG4 isotype. In some embodiments, an antibody of the disclosure is of the IgG4 isotype and comprises a mutation.

[0110] As used herein the term “KD” or “KD” refers to the equilibrium dissociation constant of a binding reaction between an antibody and an antigen. The value of KD is a numeric representation of the ratio of the antibody off-rate constant (kd) to the antibody on-rate constant (ka). The value of KD is inversely related to the binding affinity of an antibody to an antigen. The smaller the KD value the greater the affinity of the antibody for its antigen. Affinity is the strength of binding of a single molecule to its ligand and is typically measured and reported by the equilibrium dissociation constant (KD), which is used to evaluate and rank order strengths of bimolecular interactions.

[0111] As used herein, the term “kd” or “kd” (alternatively “koff ’ or “koff”) is intended to refer to the off-rate constant for the dissociation of an antibody from an antibody / antigen complex.49FH13167949.1BPX-05925The value of kd is a numeric representation of the fraction of complexes that decay or dissociate per second, and is expressed in units sec'1.

[0112] As used herein, the term “ka” or “ka” (alternatively “kon” Or “kon”) is intended to refer to the on-rate constant for the association of an antibody with an antigen. The value of ka is a numeric representation of the number of antibody / antigen complexes formed per second in a 1 molar (IM) solution of antibody and antigen, and is expressed in units M^sec'1.

[0113] As used herein, the terms “linked,” “fused”, or “fusion”, are used interchangeably. These terms refer to the joining together of two more elements or components or domains, by whatever means including chemical conjugation or recombinant means. Methods of chemical conjugation (e.g., using heterobifunctional crosslinking agents) are known in the art.

[0114] As used herein, the term “monoclonal antibody” refers to an antibody which displays a single binding specificity and affinity for a particular epitope.

[0115] As used herein, the term “nucleic acid” refers to deoxyribonucleotides or ribonucleotides and polymers thereof in either single- or double- stranded form. Unless specifically limited, the term encompasses nucleic acids containing known analogues of natural nucleotides that have similar binding properties as the reference nucleic acid and are metabolized in a manner similar to naturally occurring nucleotides. Unless otherwise indicated, a particular nucleic acid sequence also implicitly encompasses conservatively modified variants thereof (e.g., degenerate codon substitutions) and complementary sequences and as well as the sequence explicitly indicated. Specifically, degenerate codon substitutions can be achieved by generating sequences in which the third position of one or more selected (or all) codons is substituted with mixed-base and / or deoxyinosine residues (Batzer et al., Nucleic Acid Res. 19:5081, 1991; Ohtsuka et al., Biol. Chem. 260:2605-2608, 1985; and Cassol et al, 1992; Rossolini et al, Mol. Cell. Probes 8:91-98, 1994). For arginine and leucine, modifications at the second base can also be conservative. The term nucleic acid is used interchangeably with gene, cDNA, and mRNA encoded by a gene.

[0116] Polynucleotides used herein can be composed of any polyribonucleotide or poly deoxyribonucleotide, which can be unmodified RNA or DNA or modified RNA or DNA. For example, polynucleotides can be composed of single- and double-stranded DNA, DNA that is a mixture of single- and double- stranded regions, single- and double- stranded RNA, and RNA that is mixture of single- and double- stranded regions, hybrid molecules comprising DNA and RNA that can be single- stranded or, more typically, double-stranded or a mixture of single- and double-50FH13167949.1BPX-05925 stranded regions. In addition, the polynucleotide can be composed of triple-stranded regions comprising RNA or DNA or both RNA and DNA. A polynucleotide can also contain one or more modified bases or DNA or RNA backbones modified for stability or for other reasons. “Modified” bases include, for example, tritylated bases and unusual bases such as inosine. A variety of modifications can be made to DNA and RNA; thus, “polynucleotide” embraces chemically, enzymatically, or metabolically modified forms.

[0117] The term “percent identity,” in the context of two or more nucleic acid or polypeptide sequences, refer to two or more sequences or subsequences that have a specified percentage of nucleotides or amino acid residues that are the same, when compared and aligned for maximum correspondence, as measured using one of the sequence comparison algorithms described below (e.g., BLASTP and BLASTN or other algorithms available to persons of skill) or by visual inspection. Depending on the application, the “percent identity” can exist over a region of the sequence being compared, e.g., over a functional domain, or, alternatively, exist over the full length of the two sequences to be compared. For sequence comparison, typically one sequence acts as a reference sequence to which test sequences are compared. When using a sequence comparison algorithm, test and reference sequences are input into a computer, subsequence coordinates are designated, if necessary, and sequence algorithm program parameters are designated. The sequence comparison algorithm then calculates the percent sequence identity for the test sequence(s) relative to the reference sequence, based on the designated program parameters.

[0118] Optimal alignment of sequences for comparison can be conducted, e.g., by the local homology algorithm of Smith & Waterman, Adv. Appl. Math. 2:482 (1981), by the homology alignment algorithm of Needleman & Wunsch, J. Mol. Biol. 48:443 (1970), by the search for similarity method of Pearson & Lipman, Proc. Nat’l. Acad. Sci. USA 85:2444 (1988), by computerized implementations of these algorithms (GAP, BESTFIT, FASTA, and TFASTA in the Wisconsin Genetics Software Package, Genetics Computer Group, 575 Science Dr., Madison, Wis.), or by visual inspection (see generally Ausubel et al., infra). One example of an algorithm that is suitable for determining percent sequence identity and sequence similarity is the BLAST algorithm, which is described in Altschul et al., J. Mol. Biol. 215:403-410 (1990). Software for performing BLAST analyses is publicly available through the National Center for Biotechnology Information website.51FH13167949.1BPX-05925

[0119] As generally used herein, “pharmaceutically acceptable” refers to those compounds, materials, compositions, and / or dosage forms which are, within the scope of sound medical judgment, suitable for use in contact with the tissues, organs, and / or bodily fluids of human beings and animals without excessive toxicity, irritation, allergic response, or other problems or complications commensurate with a reasonable benefit / risk ratio.

[0120] As used herein, a “pharmaceutically acceptable carrier” refers to, and includes any and all solvents, dispersion media, coatings, antibacterial and antifungal agents, isotonic and absorption delaying agents, and the like that are physiologically compatible. The compositions can include a pharmaceutically acceptable salt, e.g., an acid addition salt or a base addition salt (see, e.g., Berge et al. (1977) J P harm Sci 66: 1-19).

[0121] As used herein, the term “purified” or “isolated” as applied to any of the proteins (antibodies or fragments) described herein refers to a polypeptide that has been separated or purified from components (e.g., proteins or other naturally-occurring biological or organic molecules) which naturally accompany it, e.g., other proteins, lipids, and nucleic acid in a prokaryote expressing the proteins. Typically, a polypeptide is purified when it constitutes at least 60 (e.g., at least 65, 70, 75, 80, 85, 90, 92, 95, 97, or 99) %, by weight, of the total protein in a sample.

[0122] As used herein, the term “subject” includes any human or non-human animal. For example, the methods and compositions provided herein can be used to treat a subject with a complement-associated disorder. The term “non-human animal” includes all vertebrates, e.g., mammals and non-mammals, such as non-human primates, sheep, dog, cow, chickens, amphibians, reptiles, etc. In some embodiments, the subject is a human over 18 years of age. In certain embodiments, the subject is a human over 12 years of age. In certain embodiments, the subject is a human under 12 years of age.

[0123] For nucleic acids, the term “substantial homology” indicates that two nucleic acids, or designated sequences thereof, when optimally aligned and compared, are identical, with appropriate nucleotide insertions or deletions, in at least about 80% of the nucleotides, usually at least about 90% to 95%, and more preferably at least about 98% to 99.5% of the nucleotides. Alternatively, substantial homology exists when the segments will hybridize under selective hybridization conditions, to the complement of the strand.

[0124] As used herein, the terms “therapeutically effective amount” or “therapeutically effective dose,” or similar terms used herein are intended to mean an amount of an agent (e.g., an52FH13167949.1BPX-05925 anti-C2 antibody or an antigen-binding fragment thereof, or conjugate thereof) that will elicit the desired biological or medical response (e.g., an improvement in one or more symptoms of a complement-associated disorder or condition).

[0125] As used herein, the term “regulator of complement activation (RCA) polypeptide” refers to a protein or peptide that regulates complement activation. RCA polypeptides comprise multiple repeating complement control protein (CCP) domains (also known as Sushi domains or short consensus repeats). CCP domains are composed of about 60-70 amino acids with four invariant cysteines forming disulfide bonds. CCP domains, either alone or in combination with one another, are capable of exerting the complement regulatory function of the RCA polypeptides. RCA polypeptides include decay-accelerating factor (DAF; CD55), membrane cofactor protein (MCP; CD46), complement receptor 1 (CR1; CD35), C4b binding protein (C4BP), and factor H (FH).RCA polypeptides act through a variety of mechanisms, including decay-accelerating activity (DAA; the irreversible dissociation of C3 convertases by the RCA protein) and cofactor activity (CFA; inactivation of the non-catalytic subunit (C3b / C4b) of C3 convertases by the serine protease factor I due to its recruitment onto the C3b / C4b-RCA protein complex).

[0126] The terms “treat,” “treating,” and “treatment,” as used herein, refer to therapeutic measures described herein. The methods of “treatment” employ administration to a subject, in need of such treatment, a C2 -monoclonal antibody, or fragment thereof, or a conjugate of the foregoing, of the present disclosure, for example, a subject suffering from a disorder caused by aberrant complement activation (i.e., aberrant activation of the classical, lecithin, and / or alternative pathway) to cure, delay, reduce the severity of, or ameliorate one or more symptoms of the disorder or recurring disorder, or in order to prolong the survival of a subject beyond that expected in the absence of such treatment.

[0127] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure pertains. Preferred methods and materials are described below, although methods and materials similar or equivalent to those described herein can also be used in the practice or testing of the presently disclosed methods and compositions. All publications, patent applications, patents, and other references mentioned herein are incorporated by reference in their entirety.Anti-C2 Antibodies and Antigen-Binding Fragments Thereof53FH13167949.1BPX-05925

[0128] In some aspects, the present disclosure provides antibodies, antigen binding fragments thereof, and antibody-conjugates that specifically bind to complement 2 (C2). In some aspects, the disclosure provides anti-C2 antibodies, antigen binding fragments thereof, and antibody-conjugates that are useful for treating a disease associated with the complement pathway. In some aspects, the disclosure provides anti-C2 antibodies, antigen binding fragments thereof, and antibody-conjugates that are useful for treating a disease associated with the alternative complement pathway, the classical complement pathway and / or the lecithin complement pathway.

[0129] C2 is a multidomain serine protease that provides catalytic activity to the C3 and C5 convertases of classical and lectin pathways of complement. Like C4, C2 is cleaved by Cis into two fragments, the larger of which (C2a) forms part of the C3-convertase of the classical and lecithin pathways, C4b2a. Thus C2, like C4, plays a critical role in generating the biologic activities of C3 and the terminal components C5 through C9. C2 deficiency is a relatively common complement deficiency with disease associations of increased susceptibility for infections with encapsulated bacteria, development of SLE or SLE-like disease, and slightly increased risk for atherosclerosis, among others.

[0130] In some embodiments, the anti-C2 antibody, or antigen binding fragment thereof, inhibits or prevents the binding of complement C4b to bind to C2. In some embodiments, the anti- C2 antibody, or antigen binding fragment thereof, does not bind human Factor B. In some embodiments, the anti-C2 antibody, or antigen binding fragment thereof, inhibits or prevents the binding of complement C4b to bind to C2 and does not bind human Factor B.

[0131] In some embodiments, the anti-C2 antibody, or antigen binding fragment thereof, comprises a binding affinity against C2 of from about 0.01 nM to about 50 nM (e.g., from about 0.1 nM to about 40 nM, from about 0.1 nM to about 30 nM, from about 0.1 nM to about 20 nM, from about 0.1 nM to about 10 nM, from about 0.1 nM to about 5 nM, from about 0.1 nM to about 2 nM, from about 0.1 nM to about 1 nM, from about 0.5 nM to about 1 nM, from about 0.1 nM to about 5 nM, or from about 1 nM to about 5 nM.

[0132] In some embodiments, the anti-C2 antibody, or antigen binding fragment thereof, or anti-C2 antibody-conjugate is useful for ameliorating hemolysis associated by activation of the complement system (e.g., the complement classical pathway (CP) or the complement lecithin pathway (LP)). In some embodiments, the anti-C2 antibody, or antigen binding fragment thereof, or anti-C2 antibody-conjugate comprises an IC50 for reducing CP hemolysis of about 0.1 nM to about54FH13167949.1BPX-0592535 nM (e.g., about 0.1 nM, about 0.2 nM, about 0.3 nM, about 0.4 nM, about 0.5 nM, about 0.6 nM, about 0.7 nM, about 0.8 nM, about 0.9 nM, about 1 nM, about 1.1 nM, about 1.2 nM, about 1.3 nM, about 1.4 nM, about 1.5 nM, about 1.6 nM, about 1.7 nM, about 1.8 nM, about 1.9 nM, about 2 nM, about 2.1 nM, about 2.2 nM, about 2.3 nM, about 2.4 nM, about 2.5 nM, about 2.6 nM, about 2.7 nM, about 2.8 nM, about 2.9 nM, about 3 nM, about 4 nM, about 5 nM, about 6 nM, about 7 nM, about 8 nM, about 9 nM, about 10 nM, about 15 nM, about 20 nM, about 25 nM, about 30 nM, or about 35 nM).

[0133] In some embodiments, the anti-C2 antibody, or antigen binding fragment thereof, or anti-C2 antibody-conjugate is useful for inhibiting formation of the membrane attack complex (MAC) resulting from activation of the complement system. In some embodiments, the anti-C2 antibody, or antigen binding fragment thereof, or anti-C2 antibody-conjugate comprises an IC50 for reducing CP, LP, or AP mediated formation of the MAC of about 0.1 nM to about 50 nM (e.g., 0.1 nM, about 0.5 nM, about 0.6 nM, about 0.7 nM, about 0.8 nM, about 0.9 nM, about 1 nM, about 1.1 nM, about 1.2 nM, about 1.3 nM, about 1.4 nM, about 1.5 nM, about 1.6 nM, about 1.7 nM, about 1.8 nM, about 1.9 nM, about 2 nM, about 2.1 nM, about 2.2 nM, about 2.3 nM, about 2.4 nM, about 2.5 nM, about 2.6 nM, about 2.7 nM, about 2.8 nM, about 2.9 nM, about 3 nM, about 3.1 nM, about 3.2 nM, about 3.3 nM, about 3.4 nM, about 3.5 nM, about 3.6 nM, about 3.7 nM, about 3.8 nM, about 3.9 nM, about 4 nM, about 4.1 nM, about 4.2 nM, about 4.3 nM, about 4.4 nM, about 4.5 nM, about 4.6 nM, about 4.7 nM, about 4.8 nM, about 4.9 nM, about 5 nM, about 5.1 nM, about 5.2 nM, about 5.3 nM, about 5.4 nM, about 5.5 nM, about 5.6 nM, about 5.7 nM, about 5.8 nM, about 5.9 nM, about 6 nM, about 6.1 nM, about 6.2 nM, about 6.3 nM, about 6.4 nM, about 6.5 nM, about 6.6 nM, about 6.7 nM, about 6.8 nM, about 6.9 nM, about 7 nM, about 7.1 nM, about 7.2 nM, about 7.3 nM, about 7.4 nM, about 7.5 nM, about 7.6 nM, about 7.7 nM, about 7.8 nM, about 7.9 nM, about 8 nM, about 8.1 nM, about 8.2 nM, about 8.3 nM, about 8.4 nM, about 8.5 nM, about 8.6 nM, about 8.7 nM, about 8.8 nM, about 8.9 nM, about 9 nM, about 9.1 nM, about 9.2 nM, about 9.3 nM, about 9.4 nM, about 9.5 nM, about 9.6 nM, about 9.7 nM, about 9.8 nM, about 9.9 nM, about 10 nM, about 11 nM, about 12 nM, about 13 nM, about 14 nM, about 15 nM, about 16 nM, about 17 nM, about 18 nM, about 19 nM, about 20 nM, about 21 nM, about 22 nM, about 23 nM, about 24 nM, about 25 nM, about 26 nM, about 27 nM, about 28 nM, about 29 nM, about 30 nM, about 31 nM, about 32 nM, about 33 nM, about 34 nM, about 35 nM, about 36 nM, about 37 nM, about 38 nM,55FH13167949.1BPX-05925 about 39 nM, about 40 nM, about 41 nM, about 42 nM, about 43 nM, about 44 nM, about 45 nM, about 46 nM, about 47 nM, about 48 nM, about 49 nM, or about 50 nM).

[0134] In some embodiments, the anti-C2 antibody or antigen binding fragment thereof comprises a fragment crystallizable region (Fc region). In some embodiments, the anti-C2 antibody or antigen binding fragment thereof comprises an Fc region associated to one antigen binding fragment (Fab) region (i.e., one Fab arm). In some embodiments, the anti-C2 antibody or antigen binding fragment comprises an Fc region associated to two Fab regions (i.e., two Fab arms).Variable Regions

[0135] In some embodiments, the anti-C2 antibody or antigen binding fragment comprises a light chain variable region (VL) and a heavy chain variable region (VH). In some embodiments, the VL comprises a VL complementarity determining region (CDR) 1 (CDRL1), a CDR 2 (CDRL2), and a CDR 3 (CDRL3), and the VH comprises a VH CDR 1 (CDRH1), a VH CDR 2 (CDRH2), and a VH CDR 3 (CDRH3).

[0136] The positions of the CDRs and framework regions of the antibody or antigen binding fragment thereof can be determined using various well known definitions in the art, including Kabat, Chothia, Contact, international ImMunoGeneTics database (IMGT) (on the worldwide web at http: / / www.imgt.org), AbM, and Aho (Honneger’s numbering scheme). The most commonly used method of defining CDRs is Kabat, which is based on sequence variability (Kabat, et al. Sequences of Proteins of Immunological Interest, Fifth Edition, NTH Publication No. 91-3242 (1991); Kabat and Wu Ann N Y Acad Sci 190:3, 82-93 (1971)). Chothia defines CDRs based on the location of the structural loops (Al-Lazikani et al. J. Mol. Biol., 273, 927-948 (1997); Chothia & Lesk, J. Mol. Biol., 196: 901-917 (1987); Chothia et al., Nature, 342:877-883 (1989); Chothia et al., J. Mol. Biol., 227:799-817 (1992)). Contact defines CDRs based on an analysis of complex structures available in the Protein Databank (MacCallum et al. J. Mol. Biol., 262: 732-745 (1996); Abhinandan and Martin Mol. Immunol., 45(14), 3832-9 (2008)). The IMGT system (http: / / www.imgt.org) defined CDRs are based on the IMGT numbering for all immunoglobulin and T cell receptor V-regions of all species (Lefranc et al. Nucleic Acids Res., 27(1), 209-12 (1991); Ruiz et al. Nucleic Acids Res., 28(1), 219-21 (2000); Lefranc Nucleic Acids Res., 29(1), 207-9 (2001); Lefranc et al. Dev. Comp. Immunol., 29(3), 185-203 (2005)). Aho defines CDRs based on structural alignment of an antibody’s three dimensional features (Honegger56FH13167949.1BPX-05925 et al. J. Mol. Biol., 309, 657-70 (2001)). AbM definitions are used by Oxford Molecular’s AbM antibody modelling software and the defined CDRs represent a compromise between the Kabat and Chothia numbering schemes (Protein Engineering, Design, and Selection, Whitelee, and Rees, Vol 13(12), pages 819-824 (2000), and references cited therein; Martin et al. PNAS. USA, 86: 9268-72 (1989); Martin et al. Meth. Enzymol., 203: 121-153 (1991); Pedersen et al. Immunomethods, 1: 126-136 (1992)).

[0137] In some embodiments, VH and VL sequences identified as described herein were compared to known human germline sequences from human VH genes and human VL genes (IMGT® the international ImMunoGeneTics information system® www.imgt.org) to determine CDR sequences.

[0138] In some aspects, the present disclosure provides an anti-C2 antibody, or antigen binding fragment thereof, comprising the CDRs set forth in the VH and / or VL sequences set forth in Table 4, Table 5, or Table 11, wherein the CDRs are determined by Kabat.

[0139] In some aspects, the present disclosure provides an anti-C2 antibody, or antigen binding fragment thereof, comprising the CDRs set forth in the VH and / or VL sequences set forth in Table 4, Table 5, or Table 11, wherein the CDRs are determined by Chothia.

[0140] In some aspects, the present disclosure provides an anti-C2 antibody, or antigen binding fragment thereof, comprising the CDRs set forth in the VH and / or VL sequences set forth in Table 4, Table 5, or Table 11, wherein the CDRs are determined by IMGT.

[0141] In some aspects, the present disclosure provides an anti-C2 antibody, or antigen binding fragment thereof, comprising the CDRs set forth in the VH and / or VL sequences set forth in Table 4, Table 5, or Table 11, wherein the CDRs are determined by Contact.

[0142] In some aspects, the present disclosure provides an anti-C2 antibody, or antigen binding fragment thereof, comprising the CDRs set forth in the VH and / or VL sequences set forth in Table 4, Table 5, or Table 11, wherein the CDRs are determined by AbM (Martin).

[0143] In some aspects, the present disclosure provides an anti-C2 antibody, or antigen binding fragment thereof, comprising the CDRs set forth in the VH and / or VL sequences set forth in Table 4, Table 5, or Table 11, wherein the CDRs are determined by AHo.

[0144] In a preferred aspect, the present disclosure provides an anti-C2 antibody, or antigen binding fragment thereof, comprising the CDRs set forth in the VH and / or VL sequences set forth in Table 4, Table 5, or Table 11, wherein the CDRs are determined by AbM.57FH13167949.1BPX-05925

[0145] In some embodiments, anti-C2 antibodies, or antigen binding fragments thereof, disclosed herein comprise a VL comprising CDRL1, CDRL2, and CDRL3, and a VH comprising CDRH1, CDRH2, and CDRH3, wherein: a. the CDRL1 comprises, consists essentially of, or consists of amino acids residues 24-34, 30-36, 27-32, or 24-34 of SEQ ID NOS: 40-52 or 58-70, preferably SEQ ID NOS: 40-41, 45-48, 50-52, 58, or 62-69; b. the CDRL2 comprises, consists essentially of, or consists of amino acids residues 50-56, 46-55, or 50-51 of SEQ ID NOS: 40-52 or 58-70, preferably SEQ ID NOS: 40-41, 45-48, 50-52, 58, or 62-69; c. the CDRL3 comprises, consists essentially of, or consists of amino acids residues 89-97 or 89-96 of SEQ ID NOS: 40-52 or 58-70, preferably SEQ ID NOS: 40-41, 45-48, 50-52, 58, or 62-69; d. the CDRH1 comprises, consists essentially of, or consists of amino acids residues 26-32, 31-35, 30-35, 26-33, or 25-35 of SEQ ID NOS: 35-39 or 53-57; e. the CDRH2 comprises, consists essentially of, or consists of amino acids residues 52-57, 50-66, 47-59, 51-58, or 50-59 of SEQ ID NOS: 35-39 or 53-57; and f. the CDRH3 comprises, consists essentially of, or consists of amino acids residues 99-107, 97-106, or 97-107 of SEQ ID NOS: 35-39 or 53-57.

[0146] In some embodiments, anti-C2 antibodies, or antigen binding fragments thereof, disclosed herein comprise a VL comprising CDRL1, CDRL2, and CDRL3, and a VH comprising CDRH1, CDRH2, and CDRH3, wherein the CDRL1, CDRL2, and CDRL3 comprise, consist essentially of, or consist of the amino acid sequence set forth in Table 2 or Table 3 and wherein the CDRH1, CDRH2, and CDRH3 comprise, consist essentially of, or consist of the amino acid sequence set forth in Table 1.Table 1. CDRH determinations58FH13167949.1BPX-05925Table 2. CDRL determinations59FH13167949.1BPX-05925Table 3. CDRL determinations

[0147] In some embodiments, the anti-C2 antibody, or antigen binding fragment thereof, comprises a VL comprising CDRL1 as set forth in SEQ ID NO: 184 (X1TX2TDIDDDMN), a CDRL2 set forth in SEQ ID NO: 2 (EGNTLRP), and a CDRL3 set forth in SEQ ID NO: 185 (X3QSDX4LPFT); and the VH comprises a CDRH1 set forth in SEQ ID NO: 4 (GYTFTDYNMH), a CDRH2 set forth in SEQ ID NO: 5 (YVYPX5IGGTG), and a CDRH3 set forth in SEQ ID NO: 186 (RGX6X7GIFDY), wherein Xi is I or R; X2is F or H; X3is L or Q; X4 is N or H; X5is Y or S; Xs is Y or H; X7 is D or E, and wherein at least one of X3 is Q, X5 is S, and X7 is E.60FH13167949.1BPX-05925

[0148] In some embodiments, the anti-C2 antibody, or antigen binding fragment thereof, comprises a VL comprising CDRL1 as set forth in SEQ ID NO: 1 (XsTFTDIDDDMN), a CDRL2 set forth in SEQ ID NO: 2 (EGNTLRP), and a CDRL3 set forth in SEQ ID NO: 3 (X9QSDNLPFT); and the VH comprises a CDRH1 set forth in SEQ ID NO: 4 (GYTFTDYNMH), a CDRH2 set forth in SEQ ID NO: 5 (YVYPX5IGGTG), and a CDRH3 set forth in SEQ ID NO: 6 (RGYX10GIFDY), wherein Xs is I or R; X9 is L or Q; X5 is Y or S; and X10 is D or E, and wherein at least one of X9 is Q, X5 is S, and X10 is E.

[0149] In some embodiments, the anti-C2 antibody, or antigen binding fragment thereof, comprises a VL comprising CDRL1 as set forth in SEQ ID NO: 8 (RTFTDIDDDMN), CDRL2 as set forth in SEQ ID NO: 2, CDRL3 as set forth in SEQ ID NO: 190 (QQSDHLPFT), and a VH comprising CDRH1 as set forth in SEQ ID NO: 4, CDRH2 as set forth in SEQ ID NO: 12 (YVYPSIGGTG), and CDRH3 as set forth in SEQ ID NO: 14 (RGYEGIFDY).

[0150] In some embodiments, the anti-C2 antibody, or antigen binding fragment thereof, comprises a VL comprising CDRL1 as set forth in SEQ ID NO: 188 (RTHTDIDDDMN), CDRL2 as set forth in SEQ ID NO: 2, CDRL3 as set forth in SEQ ID NO: 190, and a VH comprising CDRH1 as set forth in SEQ ID NO: 4, CDRH2 as set forth in SEQ ID NO: 12, and CDRH3 as set forth in SEQ ID NO: 14.

[0151] In some embodiments, the anti-C2 antibody, or antigen binding fragment thereof, comprises a VL comprising CDRL1 as set forth in SEQ ID NO: 8, CDRL2 as set forth in SEQ ID NO: 2, CDRL3 as set forth in SEQ ID NO: 190, and a VH comprising CDRH1 as set forth in SEQ ID NO: 4, CDRH2 as set forth in SEQ ID NO: 12, and CDRH3 as set forth in SEQ ID NO: 191 (RGHEGIFDY).

[0152] In some embodiments, the anti-C2 antibody, or antigen binding fragment thereof, comprises a VL comprising CDRL1 as set forth in SEQ ID NO: 8, CDRL2 as set forth in SEQ ID NO: 2, CDRL3 as set forth in SEQ ID NO: 189 (LQSDHLPFT), and a VH comprising CDRH1 as set forth in SEQ ID NO: 4, CDRH2 as set forth in SEQ ID NO: 12, and CDRH3 as set forth in SEQ ID NO: 14.

[0153] In some embodiments, the anti-C2 antibody, or antigen binding fragment thereof, comprises a VL comprising CDRL1 as set forth in SEQ ID NO: 8, CDRL2 as set forth in SEQ ID NO: 2, CDRL3 as set forth in SEQ ID NO: 9, and a VH comprising CDRH1 as set forth in SEQ ID NO: 4, CDRH2 as set forth in SEQ ID NO: 12, and CDRH3 as set forth in SEQ ID NO: 14.61FH13167949.1BPX-05925

[0154] In some embodiments, the anti-C2 antibody, or antigen binding fragment thereof, comprises a VL comprising CDRL1 as set forth in SEQ ID NO: 8, CDRL2 as set forth in SEQ ID NO: 2, CDRL3 as set forth in SEQ ID NO: 9, and a VH comprising CDRH1 as set forth in SEQ ID NO: 4, CDRH2 as set forth in SEQ ID NO: 12, and CDRH3 as set forth in SEQ ID NO: 191.

[0155] In some embodiments, the anti-C2 antibody, or antigen binding fragment thereof, comprises a VL comprising CDRL1 as set forth in SEQ ID NO: 8, CDRL2 as set forth in SEQ ID NO: 2, CDRL3 as set forth in SEQ ID NO: 189, and a VH comprising CDRH1 as set forth in SEQ ID NO: 4, CDRH2 as set forth in SEQ ID NO: 12, and CDRH3 as set forth in SEQ ID NO: 191.

[0156] In some embodiments, the anti-C2 antibody, or antigen binding fragment thereof, comprises a VL comprising CDRL1 as set forth in SEQ ID NO: 188, CDRL2 as set forth in SEQ ID NO: 2, CDRL3 as set forth in SEQ ID NO: 189, and a VH comprising CDRH1 as set forth in SEQ ID NO: 4, CDRH2 as set forth in SEQ ID NO: 12, and CDRH3 as set forth in SEQ ID NO: 14.

[0157] In some embodiments, the anti-C2 antibody, or antigen binding fragment thereof, comprises the CDRL1 is set forth in SEQ ID NO: 1 (XsTFTDIDDDMN), the CDRL3 is set forth in SEQ ID NO: 3 (X9QSDNLPFT), the CDRH2 is set forth in SEQ ID NO: 5 (YVYPX5IGGTG), and the CDRH3 is set forth in SEQ ID NO: 6 (RGYX10GIFDY), wherein X8is I or R; X9is L or Q; X5is Y or S; and X10 is D or E, and wherein at least one of X9is Q, X5 is S, and X10 is E.

[0158] In some embodiments, the anti-C2 antibody, or antigen binding fragment thereof, comprises a VL comprising CDRL1 as set forth in SEQ ID NO: 8, CDRL2 as set forth in SEQ ID NO: 2, CDRL3 as set forth in SEQ ID NO: 9 (LQSDNLPFT), and a VH comprising CDRH1 as set forth in SEQ ID NO: 4, CDRH2 as set forth in SEQ ID NO: 11 (YVYPYIGGTG), and CDRH3 as set forth in SEQ ID NO: 14 (RGYEGIFDY).

[0159] In some embodiments, the anti-C2 antibody, or antigen binding fragment thereof, comprises a VL comprising CDRL1 as set forth in SEQ ID NO: 8, CDRL2 as set forth in SEQ ID NO: 2, CDRL3 as set forth in SEQ ID NO: 9, and a VH comprising CDRH1 as set forth in SEQ ID NO: 4, CDRH2 as set forth in SEQ ID NO: 12, and CDRH3 as set forth in SEQ ID NO: 13 (RGYDGIFDY).

[0160] In some embodiments, the anti-C2 antibody, or antigen binding fragment thereof, comprises a VL comprising CDRL1 as set forth in SEQ ID NO: 8, CDRL2 as set forth in SEQ ID NO: 2, CDRL3 as set forth in SEQ ID NO: 9, and a VH comprising CDRH1 as set forth in SEQ ID NO: 4, CDRH2 as set forth in SEQ ID NO: 12, and CDRH3 as set forth in SEQ ID NO: 14.62FH13167949.1BPX-05925

[0161] In some embodiments, the anti-C2 antibody, or antigen binding fragment thereof, comprises a VL comprising CDRL1 as set forth in SEQ ID NO: 8, CDRL2 as set forth in SEQ ID NO: 2, CDRL3 as set forth in SEQ ID NO: 10 (QQSDNLPFT), and a VH comprising CDRH1 as set forth in SEQ ID NO: 4, CDRH2 as set forth in SEQ ID NO: 12, and CDRH3 as set forth in SEQ ID NO: 14.

[0162] In some embodiments, the anti-C2 antibody, or antigen binding fragment thereof, comprises a VL comprising CDRL1 as set forth in SEQ ID NO: 7 (ITFTDIDDDMN), CDRL2 as set forth in SEQ ID NO: 2, CDRL3 as set forth in SEQ ID NO: 9, and a VH comprising CDRH1 as set forth in SEQ ID NO: 4, CDRH2 as set forth in SEQ ID NO: 12, and CDRH3 as set forth in SEQ ID NO: 14.

[0163] In some embodiments, the anti-C2 antibody, or antigen binding fragment thereof, comprises a VL comprising CDRL1 as set forth in SEQ ID NO: 7, CDRL2 as set forth in SEQ ID NO: 2, CDRL3 as set forth in SEQ ID NO: 9, and a VH comprising CDRH1 as set forth in SEQ ID NO: 4, CDRH2 as set forth in SEQ ID NO: 11, and CDRH3 as set forth in SEQ ID NO: 14.

[0164] In some embodiments, the anti-C2 antibody, or antigen binding fragment thereof, comprises a VL comprising CDRL1 as set forth in SEQ ID NO: 7, CDRL2 as set forth in SEQ ID NO: 2, CDRL3 as set forth in SEQ ID NO: 9, and a VH comprising CDRH1 as set forth in SEQ ID NO: 4, CDRH2 as set forth in SEQ ID NO: 12, and CDRH3 as set forth in SEQ ID NO: 13.

[0165] In some embodiments, the anti-C2 antibody, or antigen binding fragment thereof, comprises a VL comprising CDRL1 as set forth in SEQ ID NO: 7, CDRL2 as set forth in SEQ ID NO: 2, CDRL3 as set forth in SEQ ID NO: 10, and a VH comprising CDRH1 as set forth in SEQ ID NO: 4, CDRH2 as set forth in SEQ ID NO: 12, and CDRH3 as set forth in SEQ ID NO: 14.

[0166] In some embodiments, the anti-C2 antibody, or antigen binding fragment thereof, comprises a VL comprising CDRL1 as set forth in SEQ ID NO: 7, CDRL2 as set forth in SEQ ID NO: 2, CDRL3 as set forth in SEQ ID NO: 10, and a VH comprising CDRH1 as set forth in SEQ ID NO: 4, CDRH2 as set forth in SEQ ID NO: 12, and CDRH3 as set forth in SEQ ID NO: 13.

[0167] In some embodiments, the antibody, or antigen binding fragment thereof, comprises a VL comprising at least one framework region (VL FR) and a VH comprising at least one framework region (VH FR).

[0168] In some embodiments, the at least on VL FR is selected from SEQ ID Nos: 15, 16, 17, 18, and 187.63FH13167949.1BPX-05925

[0169] In some embodiments, the at least one VL FR is selected from SEQ ID Nos: 15-18. In some embodiments, the VL comprises a FR1 region selected from SEQ ID Nos: 23, 24, 25, 26, and 27, a FR2 region selected from SEQ ID Nos: 28 and 29, a FR3 region selected from SEQ ID Nos: 30, 31, and 32, and a FR4 region set forth in SEQ ID NO: 18.

[0170] In some embodiments, the VL comprises a FR1 region selected from SEQ ID Nos: 23, 24, 25, 26, and 27, a FR2 region selected from SEQ ID Nos: 28 and 29, a FR3 region selected from SEQ ID Nos: 30, 31, 32, 192, and 193 and a FR4 region set forth in SEQ ID NO: 18.

[0171] In some embodiments, the VL comprises a FR1 region set forth in SEQ ID NO: 23, a FR2 region set forth in SEQ ID NO: 28, a FR3 region set forth in SEQ ID NO: 30, and a FR4 region set forth in SEQ ID NO: 18.

[0172] In some embodiments, the VL comprises a FR1 region set forth in SEQ ID NO: 23, a FR2 region set forth in SEQ ID NO: 28, a FR3 region set forth in SEQ ID NO: 192, and a FR4 region set forth in SEQ ID NO: 18.

[0173] In some embodiments, the VL comprises a FR1 region set forth in SEQ ID NO: 24, a FR2 region set forth in SEQ ID NO: 28, a FR3 region set forth in SEQ ID NO: 30, and a FR4 region set forth in SEQ ID NO: 18.

[0174] In some embodiments, the VL comprises a FR1 region set forth in SEQ ID NO: 24, a FR2 region set forth in SEQ ID NO: 28, a FR3 region set forth in SEQ ID NO: 192, and a FR4 region set forth in SEQ ID NO: 18.

[0175] In some embodiments, the VL comprises a FR1 region set forth in SEQ ID NO: 24, a FR2 region set forth in SEQ ID NO: 29, a FR3 region set forth in SEQ ID NO: 31, and a FR4 region set forth in SEQ ID NO: 18.

[0176] In some embodiments, the VL comprises a FR1 region set forth in SEQ ID NO: 24, a FR2 region set forth in SEQ ID NO: 29, a FR3 region set forth in SEQ ID NO: 32, and a FR4 region set forth in SEQ ID NO: 18.

[0177] In some embodiments, the VL comprises a FR1 region set forth in SEQ ID NO: 24, a FR2 region set forth in SEQ ID NO: 29, a FR3 region set forth in SEQ ID NO: 193, and a FR4 region set forth in SEQ ID NO: 18.

[0178] In some embodiments, the at least one VH FR is selected from SEQ ID Nos: 19-22. In some embodiments, the VH comprises a FR1 region selected from SEQ ID Nos: 33 and 34, a64FH13167949.1BPX-05925FR2 region set forth in SEQ ID NO: 20, a FR3 region set forth in SEQ ID NO: 21, and a FR4 region set forth in SEQ ID NO: 22.

[0179] In some embodiments, the VH comprises a FR1 region set forth in SEQ ID NO: 33, a FR2 region set forth in SEQ ID NO: 20, a FR3 region set forth in SEQ ID NO: 21, and a FR4 region set forth in SEQ ID NO: 22.

[0180] In some embodiments, the VH comprises a FR1 region set forth in SEQ ID NO: 34, a FR2 region set forth in SEQ ID NO: 20, a FR3 region set forth in SEQ ID NO: 21, and a FR4 region set forth in SEQ ID NO: 22.

[0181] In some embodiments, the VL comprises one to four framework regions (VL FR1- FR4) and the VH comprises one to four framework regions (VH FR1-FR4).

[0182] In some embodiments, the VH and the VL comprise amino acid sequences having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequences selected from: (a) SEQ ID NOs: 36 and 50, respectively, (b) SEQ ID NOs: 37 and 50, respectively, (c) SEQ ID NOs: 38 and 50, respectively, (d) SEQ ID NOs: 38 and 51, respectively, (e) SEQ ID NOs: 38 and 52, respectively, (f) SEQ ID NOs: 36 and 40, respectively, (g) SEQ ID NOs: 36 and 41, respectively, (h) SEQ ID NOs: 36 and 42, respectively, (i) SEQ ID NOs: 36 and 43, respectively, (j) SEQ ID NOs: 36 and 44, respectively, (k) SEQ ID NOs: 37 and 40, respectively, (1) SEQ ID NOs: 38 and 40, respectively, (m) SEQ ID NOs: 38 and 41, respectively, (n) SEQ ID NOs: 38 and 45, respectively, (o) SEQ ID NOs: 38 and 46, respectively, (p) SEQ ID NOs: 38 and 47, respectively, (q) SEQ ID NOs: 38 and 48, respectively, (r) SEQ ID NOs: 37 and 46, respectively, and (s) SEQ ID NOs: 37 and 48, respectively.

[0183] In some embodiments, the VH and the VL comprise amino acid sequences having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequences selected from: (a) SEQ ID NOs: 35 and 40, respectively, (b) SEQ ID NOs: 35 and 49, respectively, (c) SEQ ID NOs: 35 and 50, respectively, (d) SEQ ID NOs: 35 and 41, respectively, (e) SEQ ID NOs: 35 and 46, respectively, (f) SEQ ID NOs: 36 and 50, respectively, (g) SEQ ID NOs: 36 and 40, respectively, (h) SEQ ID NOs: 36 and 41, respectively, (i) SEQ ID NOs: 36 and 42, respectively, (j) SEQ ID NOs: 36 and 43, respectively, (k) SEQ ID NOs: 36 and 44, respectively, (1) SEQ ID NOs: 37 and 50, respectively, (m) SEQ ID NOs: 37 and 40, respectively, (n) SEQ ID NOs: 37 and 46, respectively, (o) SEQ ID NOs: 37 and 48, respectively, (p) SEQ ID NOs: 38 and 50, respectively, (q) SEQ ID NOs: 38 and 51, respectively, (r) SEQ ID NOs: 38 and65FH13167949.1BPX-0592552, respectively, (s) SEQ ID NOs: 38 and 40, respectively, (t) SEQ ID NOs: 38 and 41, respectively, (u) SEQ ID NOs: 38 and 45, respectively, (v) SEQ ID NOs: 38 and 46, respectively, (w) SEQ ID NOs: 38 and 47, respectively, (x) SEQ ID NOs: 38 and 48, respectively, and (y) SEQ ID NOs: 39 and 40, respectively.

[0184] In some embodiments, the VH and the VL comprise amino acid sequences having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequences selected from: (a) SEQ ID NOs: 36 and 50, respectively, (b) SEQ ID NOs: 37 and 50, respectively, (c) SEQ ID NOs: 38 and 50, respectively, (d) SEQ ID NOs: 38 and 51, respectively, (e) SEQ ID NOs: 38 and 52, respectively, (f) SEQ ID NOs: 36 and 40, respectively, (g) SEQ ID NOs: 36 and 41, respectively, (h) SEQ ID NOs: 36 and 42, respectively, (i) SEQ ID NOs: 36 and 43, respectively, (j) SEQ ID NOs: 36 and 44, respectively, (k) SEQ ID NOs: 37 and 40, respectively, (1) SEQ ID NOs: 38 and 40, respectively, (m) SEQ ID NOs: 38 and 41, respectively, (n) SEQ ID NOs: 38 and 45, respectively, (o) SEQ ID NOs: 38 and 46, respectively, (p) SEQ ID NOs: 38 and 47, respectively, (q) SEQ ID NOs: 38 and 48, respectively, (r) SEQ ID NOs: 37 and 46, respectively, (s) SEQ ID NOs: 37 and 48, respectively, (t) SEQ ID NOs: 38 and 195, respectively, (u) SEQ ID NOs: 38 and 196, respectively, (v) SEQ ID NOs: 38 and 197, respectively, (w) SEQ ID NOs: 194 and 41, respectively, (x) SEQ ID NOs: 194 and 195, respectively, (y) SEQ ID NOs: 38 and 198, respectively, (z) SEQ ID NOs: 38 and 199, respectively, (aa) SEQ ID NOs: 194 and 197, respectively, (bb) SEQ ID NOs: 38 and 200, respectively, (cc) SEQ ID NOs: 38 and 201, respectively, (dd) SEQ ID NOs: 194 and 200, respectively, (ee) SEQ ID NOs: 38 and 202, respectively, (ff) SEQ ID NOs: 38 and 203, respectively, and (gg) SEQ ID NOs: 194 and 202, respectively.

[0185] In some embodiments, the VH and the VL comprise amino acid sequences having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequences selected from: (a) SEQ ID NOs: 35 and 40, respectively, (b) SEQ ID NOs: 35 and 49, respectively, (c) SEQ ID NOs: 35 and 50, respectively, (d) SEQ ID NOs: 35 and 41, respectively, (e) SEQ ID NOs: 35 and 46, respectively, (f) SEQ ID NOs: 36 and 50, respectively, (g) SEQ ID NOs: 36 and 40, respectively, (h) SEQ ID NOs: 36 and 41, respectively, (i) SEQ ID NOs: 36 and 42, respectively, (j) SEQ ID NOs: 36 and 43, respectively, (k) SEQ ID NOs: 36 and 44, respectively, (1) SEQ ID NOs: 37 and 50, respectively, (m) SEQ ID NOs: 37 and 40, respectively, (n) SEQ ID NOs: 37 and 46, respectively, (o) SEQ ID NOs: 37 and 48, respectively, (p) SEQ ID66FH13167949.1BPX-05925NOs: 38 and 50, respectively, (q) SEQ ID NOs: 38 and 51, respectively, (r) SEQ ID NOs: 38 and 52, respectively, (s) SEQ ID NOs: 38 and 40, respectively, (t) SEQ ID NOs: 38 and 41, respectively, (u) SEQ ID NOs: 38 and 45, respectively, (v) SEQ ID NOs: 38 and 46, respectively, (w) SEQ ID NOs: 38 and 47, respectively, (x) SEQ ID NOs: 38 and 48, respectively, (y) SEQ ID NOs: 39 and 40, respectively, (z) SEQ ID NOs: 38 and 195, respectively, (aa) SEQ ID NOs: 38 and 196, respectively, (bb) SEQ ID NOs: 38 and 197, respectively, (cc) SEQ ID NOs: 194 and 41, respectively, (dd) SEQ ID NOs: 194 and 195, respectively, (ee) SEQ ID NOs: 38 and 198, respectively, (ff) SEQ ID NOs: 38 and 199, respectively, (gg) SEQ ID NOs: 194 and 197, respectively, (hh) SEQ ID NOs: 38 and 200, respectively, (ii) SEQ ID NOs: 38 and 201, respectively, (jj) SEQ ID NOs: 194 and 200, respectively, (kk) SEQ ID NOs: 38 and 202, respectively, (11) SEQ ID NOs: 38 and 203, respectively, and (mm) SEQ ID NOs: 194 and 202, respectively.

[0186] In some embodiments, the VH and the VL comprise the amino acid sequences selected from: (a) SEQ ID NOs: 36 and 50, respectively, (b) SEQ ID NOs: 37 and 50, respectively, (c) SEQ ID NOs: 38 and 50, respectively, (d) SEQ ID NOs: 38 and 51, respectively, (e) SEQ ID NOs: 38 and 52, respectively, (f) SEQ ID NOs: 36 and 40, respectively, (g) SEQ ID NOs: 36 and 41, respectively, (h) SEQ ID NOs: 36 and 42, respectively, (i) SEQ ID NOs: 36 and 43, respectively, (j) SEQ ID NOs: 36 and 44, respectively, (k) SEQ ID NOs: 37 and 40, respectively, (1) SEQ ID NOs: 38 and 40, respectively, (m) SEQ ID NOs: 38 and 41, respectively, (n) SEQ ID NOs: 38 and 45, respectively, (o) SEQ ID NOs: 38 and 46, respectively, (p) SEQ ID NOs: 38 and 47, respectively, (q) SEQ ID NOs: 38 and 48, respectively, (r) SEQ ID NOs: 37 and 46, respectively, and (s) SEQ ID NOs: 37 and 48, respectively.

[0187] In some embodiments, the VH and the VL comprise the amino acid sequences selected from: (a) SEQ ID NOs: 35 and 40, respectively, (b) SEQ ID NOs: 35 and 49, respectively, (c) SEQ ID NOs: 35 and 50, respectively, (d) SEQ ID NOs: 35 and 41, respectively, (e) SEQ ID NOs: 35 and 46, respectively, (f) SEQ ID NOs: 36 and 50, respectively, (g) SEQ ID NOs: 36 and 40, respectively, (h) SEQ ID NOs: 36 and 41, respectively, (i) SEQ ID NOs: 36 and 42, respectively, (j) SEQ ID NOs: 36 and 43, respectively, (k) SEQ ID NOs: 36 and 44, respectively, (1) SEQ ID NOs: 37 and 50, respectively, (m) SEQ ID NOs: 37 and 40, respectively, (n) SEQ ID NOs: 37 and 46, respectively, (o) SEQ ID NOs: 37 and 48, respectively, (p) SEQ ID NOs: 38 and 50, respectively, (q) SEQ ID NOs: 38 and 51, respectively, (r) SEQ ID NOs: 38 and 52, respectively,67FH13167949.1BPX-05925(s) SEQ ID NOs: 38 and 40, respectively, (t) SEQ ID NOs: 38 and 41, respectively, (u) SEQ ID NOs: 38 and 45, respectively, (v) SEQ ID NOs: 38 and 46, respectively, (w) SEQ ID NOs: 38 and 47, respectively, (x) SEQ ID NOs: 38 and 48, respectively, and (y) SEQ ID NOs: 39 and 40, respectively.

[0188] In some embodiments, the VH and the VL comprise the amino acid sequences selected from: (a) SEQ ID NOs: 36 and 50, respectively, (b) SEQ ID NOs: 37 and 50, respectively, (c) SEQ ID NOs: 38 and 50, respectively, (d) SEQ ID NOs: 38 and 51, respectively, (e) SEQ ID NOs: 38 and 52, respectively, (f) SEQ ID NOs: 36 and 40, respectively, (g) SEQ ID NOs: 36 and 41, respectively, (h) SEQ ID NOs: 36 and 42, respectively, (i) SEQ ID NOs: 36 and 43, respectively, (j) SEQ ID NOs: 36 and 44, respectively, (k) SEQ ID NOs: 37 and 40, respectively, (1) SEQ ID NOs: 38 and 40, respectively, (m) SEQ ID NOs: 38 and 41, respectively, (n) SEQ ID NOs: 38 and 45, respectively, (o) SEQ ID NOs: 38 and 46, respectively, (p) SEQ ID NOs: 38 and 47, respectively, (q) SEQ ID NOs: 38 and 48, respectively, (r) SEQ ID NOs: 37 and 46, respectively, (s) SEQ ID NOs: 37 and 48, respectively, (t) SEQ ID NOs: 38 and 195, respectively, (u) SEQ ID NOs: 38 and 196, respectively, (v) SEQ ID NOs: 38 and 197, respectively, (w) SEQ ID NOs: 194 and 41, respectively, (x) SEQ ID NOs: 194 and 195, respectively, (y) SEQ ID NOs: 38 and 198, respectively, (z) SEQ ID NOs: 38 and 199, respectively, (aa) SEQ ID NOs: 194 and 197, respectively, (bb) SEQ ID NOs: 38 and 200, respectively, (cc) SEQ ID NOs: 38 and 201, respectively, (dd) SEQ ID NOs: 194 and 200, respectively, (ee) SEQ ID NOs: 38 and 202, respectively, (ff) SEQ ID NOs: 38 and 203, respectively, and (gg) SEQ ID NOs: 194 and 202, respectively.

[0189] In some embodiments, the VH and the VL comprise the amino acid sequences selected from: (a) SEQ ID NOs: 35 and 40, respectively, (b) SEQ ID NOs: 35 and 49, respectively, (c) SEQ ID NOs: 35 and 50, respectively, (d) SEQ ID NOs: 35 and 41, respectively, (e) SEQ ID NOs: 35 and 46, respectively, (f) SEQ ID NOs: 36 and 50, respectively, (g) SEQ ID NOs: 36 and 40, respectively, (h) SEQ ID NOs: 36 and 41, respectively, (i) SEQ ID NOs: 36 and 42, respectively, (j) SEQ ID NOs: 36 and 43, respectively, (k) SEQ ID NOs: 36 and 44, respectively, (1) SEQ ID NOs: 37 and 50, respectively, (m) SEQ ID NOs: 37 and 40, respectively, (n) SEQ ID NOs: 37 and 46, respectively, (o) SEQ ID NOs: 37 and 48, respectively, (p) SEQ ID NOs: 38 and 50, respectively, (q) SEQ ID NOs: 38 and 51, respectively, (r) SEQ ID NOs: 38 and 52, respectively, (s) SEQ ID NOs: 38 and 40, respectively, (t) SEQ ID NOs: 38 and 41, respectively, (u) SEQ ID68FH13167949.1BPX-05925NOs: 38 and 45, respectively, (v) SEQ ID NOs: 38 and 46, respectively, (w) SEQ ID NOs: 38 and 47, respectively, (x) SEQ ID NOs: 38 and 48, respectively, (y) SEQ ID NOs: 39 and 40, respectively, (z) SEQ ID NOs: 38 and 195, respectively, (aa) SEQ ID NOs: 38 and 196, respectively, (bb) SEQ ID NOs: 38 and 197, respectively, (cc) SEQ ID NOs: 194 and 41, respectively, (dd) SEQ ID NOs: 194 and 195, respectively, (ee) SEQ ID NOs: 38 and 198, respectively, (ff) SEQ ID NOs: 38 and 199, respectively, (gg) SEQ ID NOs: 194 and 197, respectively, (hh) SEQ ID NOs: 38 and 200, respectively, (ii) SEQ ID NOs: 38 and 201, respectively, (jj) SEQ ID NOs: 194 and 200, respectively, (kk) SEQ ID NOs: 38 and 202, respectively, (11) SEQ ID NOs: 38 and 203, respectively, and (mm) SEQ ID NOs: 194 and 202, respectively.

[0190] In some embodiments, the VH and VL comprise amino acid sequences having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequences set forth in SEQ ID NOs: 35 and 40 respectively. In some embodiments, the VH and VL comprise the amino acid sequences set forth in SEQ ID NOs: 35 and 40 respectively.

[0191] In some embodiments, the VH and VL comprise amino acid sequences having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequences set forth in SEQ ID NOs: 35 and 49 respectively. In some embodiments, the VH and VL comprise the amino acid sequences set forth in SEQ ID NOs: 35 and 49 respectively.

[0192] In some embodiments, the VH and VL comprise amino acid sequences having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequences set forth in SEQ ID NOs: 35 and 50 respectively. In some embodiments, the VH and VL comprise the amino acid sequences set forth in SEQ ID NOs: 35 and 50 respectively.

[0193] In some embodiments, the VH and VL comprise amino acid sequences having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequences set forth in SEQ ID NOs: 35 and 41 respectively. In some embodiments, the VH and VL comprise the amino acid sequences set forth in SEQ ID NOs: 35 and 41 respectively.

[0194] In some embodiments, the VH and VL comprise amino acid sequences having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequences set forth in SEQ ID NOs: 35 and 46 respectively. In some embodiments, the VH and VL comprise the amino acid sequences set forth in SEQ ID NOs: 35 and 46 respectively.69FH13167949.1BPX-05925

[0195] In some embodiments, the VH and VL comprise amino acid sequences having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequences set forth in SEQ ID NOs: 39 and 40 respectively. In some embodiments, the VH and VL comprise the amino acid sequences set forth in SEQ ID NOs: 39 and 40 respectively.

[0196] In some embodiments, the VH and a VL comprise amino acid sequences having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequences set forth in SEQ ID NOs: 36 and 50, respectively. In some embodiments, the VH and a VL comprise the amino acid sequences set forth in SEQ ID NOs: 36 and 50, respectively.

[0197] In some embodiments, the VH and a VL comprise amino acid sequences having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequences set forth in SEQ ID NOs: 37 and 50, respectively. In some embodiments, the VH and a VL comprise the amino acid sequences set forth in SEQ ID NOs: 37 and 50, respectively.

[0198] In some embodiments, the VH and a VL comprise amino acid sequences having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequences set forth in SEQ ID NOs: 38 and 50, respectively. In some embodiments, the VH and a VL comprise the amino acid sequences set forth in SEQ ID NOs: 38 and 50, respectively.

[0199] In some embodiments, the VH and a VL comprise amino acid sequences having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequences set forth in SEQ ID NOs: 38 and 51, respectively. In some embodiments, the VH and a VL comprise the amino acid sequences set forth in SEQ ID NOs: 38 and 51, respectively.

[0200] In some embodiments, the VH and a VL comprise amino acid sequences having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequences set forth in SEQ ID NOs: 38 and 52, respectively. In some embodiments, the VH and a VL comprise the amino acid sequences set forth in SEQ ID NOs: 38 and 52, respectively.

[0201] In some embodiments, the VH and a VL comprise amino acid sequences having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequences set forth in SEQ ID NOs: 36 and 40, respectively. In some embodiments, the VH and a VL comprise the amino acid sequences set forth in SEQ ID NOs: 36 and 40, respectively.

[0202] In some embodiments, the VH and a VL comprise amino acid sequences having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid70FH13167949.1BPX-05925 sequences set forth in SEQ ID NOs: 36 and 41, respectively. In some embodiments, the VH and a VL comprise the amino acid sequences set forth in SEQ ID NOs: 36 and 41, respectively.

[0203] In some embodiments, the VH and a VL comprise amino acid sequences having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequences set forth in SEQ ID NOs: 36 and 42, respectively. In some embodiments, the VH and a VL comprise the amino acid sequences set forth in SEQ ID NOs: 36 and 42, respectively.

[0204] In some embodiments, the VH and a VL comprise amino acid sequences having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequences set forth in SEQ ID NOs: 36 and 43, respectively. In some embodiments, the VH and a VL comprise the amino acid sequences set forth in SEQ ID NOs: 36 and 43, respectively.

[0205] In some embodiments, the VH and a VL comprise amino acid sequences having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequences set forth in SEQ ID NOs: 36 and 44, respectively. In some embodiments, the VH and a VL comprise the amino acid sequences set forth in SEQ ID NOs: 36 and 44, respectively.

[0206] In some embodiments, the VH and a VL comprise amino acid sequences having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequences set forth in SEQ ID NOs: 37 and 40, respectively. In some embodiments, the VH and a VL comprise the amino acid sequences set forth in SEQ ID NOs: 37 and 40, respectively.

[0207] In some embodiments, the VH and a VL comprise amino acid sequences having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequences set forth in SEQ ID NOs: 38 and 40, respectively. In some embodiments, the VH and a VL comprise the amino acid sequences set forth in SEQ ID NOs: 38 and 40, respectively.

[0208] In some embodiments, the VH and a VL comprise amino acid sequences having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequences set forth in SEQ ID NOs: 38 and 41 respectively. In some embodiments, the VH and a VL comprise the amino acid sequences set forth in SEQ ID NOs: 38 and 41, respectively.

[0209] In some embodiments, the VH and a VL comprise amino acid sequences having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequences set forth in SEQ ID NOs: 38 and 45 respectively. In some embodiments, the VH and a VL comprise the amino acid sequences set forth in SEQ ID NOs: 38 and 45, respectively.71FH13167949.1BPX-05925

[0210] In some embodiments, the VH and a VL comprise amino acid sequences having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequences set forth in SEQ ID NOs: 38 and 46 respectively. In some embodiments, the VH and a VL comprise the amino acid sequences set forth in SEQ ID NOs: 38 and 46, respectively.

[0211] In some embodiments, the VH and a VL comprise amino acid sequences having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequences set forth in SEQ ID NOs: 38 and 47 respectively. In some embodiments, the VH and a VL comprise the amino acid sequences set forth in SEQ ID NOs: 38 and 47, respectively.

[0212] In some embodiments, the VH and a VL comprise amino acid sequences having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequences set forth in SEQ ID NOs: 38 and 48 respectively. In some embodiments, the VH and a VL comprise the amino acid sequences set forth in SEQ ID NOs: 38 and 48, respectively.

[0213] In some embodiments, the VH and a VL comprise amino acid sequences having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequences set forth in SEQ ID NOs: 37 and 46 respectively. In some embodiments, the VH and a VL comprise the amino acid sequences set forth in SEQ ID NOs: 37 and 46, respectively.

[0214] In some embodiments, the VH and a VL comprise amino acid sequences having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequences set forth in SEQ ID NOs: 37 and 48 respectively. In some embodiments, the VH and a VL comprise the amino acid sequences set forth in SEQ ID NOs: 37 and 48, respectively.

[0215] In some embodiments, the VH and a VL comprise amino acid sequences having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequences set forth in SEQ ID NOs: 38 and 195 respectively. In some embodiments, the VH and a VL comprise the amino acid sequences set forth in SEQ ID NOs: 38 and 195, respectively.

[0216] In some embodiments, the VH and a VL comprise amino acid sequences having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequences set forth in SEQ ID NOs: 38 and 196 respectively. In some embodiments, the VH and a VL comprise the amino acid sequences set forth in SEQ ID NOs: 38 and 196, respectively.

[0217] In some embodiments, the VH and a VL comprise amino acid sequences having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid72FH13167949.1BPX-05925 sequences set forth in SEQ ID NOs: 38 and 197 respectively. In some embodiments, the VH and a VL comprise the amino acid sequences set forth in SEQ ID NOs: 38 and 197, respectively.

[0218] In some embodiments, the VH and a VL comprise amino acid sequences having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequences set forth in SEQ ID NOs: 194 and 41 respectively. In some embodiments, the VH and a VL comprise the amino acid sequences set forth in SEQ ID NOs: 194 and 41, respectively.

[0219] In some embodiments, the VH and a VL comprise amino acid sequences having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequences set forth in SEQ ID NOs: 194 and 195 respectively. In some embodiments, the VH and a VL comprise the amino acid sequences set forth in SEQ ID NOs: 194 and 195, respectively.

[0220] In some embodiments, the VH and a VL comprise amino acid sequences having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequences set forth in SEQ ID NOs: 38 and 198 respectively. In some embodiments, the VH and a VL comprise the amino acid sequences set forth in SEQ ID NOs: 38 and 198, respectively.

[0221] In some embodiments, the VH and a VL comprise amino acid sequences having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequences set forth in SEQ ID NOs: 38 and 199 respectively. In some embodiments, the VH and a VL comprise the amino acid sequences set forth in SEQ ID NOs: 38 and 199, respectively.

[0222] In some embodiments, the VH and a VL comprise amino acid sequences having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequences set forth in SEQ ID NOs: 194 and 197 respectively. In some embodiments, the VH and a VL comprise the amino acid sequences set forth in SEQ ID NOs: 194 and 197, respectively.

[0223] In some embodiments, the VH and a VL comprise amino acid sequences having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequences set forth in SEQ ID NOs: 38 and 200 respectively. In some embodiments, the VH and a VL comprise the amino acid sequences set forth in SEQ ID NOs: 38 and 200, respectively.

[0224] In some embodiments, the VH and a VL comprise amino acid sequences having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequences set forth in SEQ ID NOs: 38 and 201 respectively. In some embodiments, the VH and a VL comprise the amino acid sequences set forth in SEQ ID NOs: 38 and 201, respectively.73FH13167949.1BPX-05925

[0225] In some embodiments, the VH and a VL comprise amino acid sequences having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequences set forth in SEQ ID NOs: 194 and 200 respectively. In some embodiments, the VH and a VL comprise the amino acid sequences set forth in SEQ ID NOs: 194 and 200, respectively.

[0226] In some embodiments, the VH and a VL comprise amino acid sequences having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequences set forth in SEQ ID NOs: 38 and 202 respectively. In some embodiments, the VH and a VL comprise the amino acid sequences set forth in SEQ ID NOs: 38 and 202, respectively.

[0227] In some embodiments, the VH and a VL comprise amino acid sequences having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequences set forth in SEQ ID NOs: 38 and 203 respectively. In some embodiments, the VH and a VL comprise the amino acid sequences set forth in SEQ ID NOs: 38 and 203, respectively.

[0228] In some embodiments, the VH and a VL comprise amino acid sequences having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequences set forth in SEQ ID NOs: 194 and 202 respectively. In some embodiments, the VH and a VL comprise the amino acid sequences set forth in SEQ ID NOs: 194 and 202, respectively.

[0229] In certain aspects, the disclosure provides an anti-C2 antibody or antigen binding fragment thereof comprising a VL comprising a CDRL1 set forth in SEQ ID NO: 184 (X1TX2TDIDDDMN), wherein Xi is I or R; X2is F or H, a CDRL2 set forth in SEQ ID NO: 2 (EGNTLRP), a CDRL3 set forth in SEQ ID NO: 185 (X3QSDX4LPFT), wherein X3is L or Q; X4is N or H, a VL FR1 comprising an amino acid sequence having at least 95% identity to SEQ ID NO: 15 (ETTVTQSPSSLSX11SVGX12RVTIX13C), wherein Xu is M or A; X12 is D or E; X13 is T or R, a VL FR2 comprising an amino acid sequence having at least 95% identity to SEQ ID NO: 16 (WYQQKPGKX14PKLLIS), wherein X14 is P or A, a VL FR3 comprising an amino acid sequence having at least 95% identity to SEQ ID NO: 187 (GVPSRFSX15SGX16GTDFTFTISSMQPEDX17ATYYC), wherein X15 is S or G; Xi6is Y or H; X17 is V or F, a VL FR4 comprising an amino acid sequence having at least 95% identity to SEQ ID NO: 18 (FGQGTKLEIK), and a VH comprising a CDRH1 set forth in SEQ ID NO: 4 (GYTFTDYNMH), a CDRH2 set forth in SEQ ID NO: 5 (YVYPX5IGGTG), wherein X5is Y or S, a CDRH3 set forth in SEQ ID NO: 186 (RGX6X7GIFDY), wherein X6is Y or H, X7is D or E, a VH FR1 comprising an amino acid sequence having at least 95% identity to SEQ ID NO: 1974FH13167949.1BPX-05925(X20VQLVQSGAEVKKPGASVKISCKAS), wherein X20is E or Q, a VH FR2 comprising an amino acid sequence having at least 95% identity to SEQ ID NO: 20 (WVRQAPGQGLEWIG), a VH FR3 comprising an amino acid sequence having at least 95% identity to SEQ ID NO: 21 (YNQKFKNRATLTVDTSTSTAYMELSSLRSEDTAVYYCTR), and a VH FR4 comprising an amino acid sequence having at least 95% identity to SEQ ID NO: 22 (WGQGTTLTVSS).

[0230] In certain aspects, the disclosure provides an anti-C2 antibody or antigen binding fragment thereof comprising a VL comprising a CDRL1 set forth in SEQ ID NO: 1 (XsTFTDIDDDMN), wherein X8is I or R, a CDRL2 set forth in SEQ ID NO: 2 (EGNTLRP), a CDRL3 set forth in SEQ ID NO: 3 (X9QSDNLPFT), wherein X9 is L or Q, a VL FR1 comprising an amino acid sequence having at least 95% identity to SEQ ID NO: 15 (ETTVTQSPSSLSXnSVGXi2RVTIXi3C), wherein Xu is M or A; Xi2is D or E; X13 is T or R, a VL FR2 comprising an amino acid sequence having at least 95% identity to SEQ ID NO: 16 (WYQQKPGKX14PKLLIS), wherein X14 is P or A, a VL FR3 comprising an amino acid sequence having at least 95% identity to SEQ ID NO: 17 (GVPSRFSX18SGYGTDFTFTISSMQPEDX19ATYYC), wherein Xi8is S or G; X19 is V or F, and a VL FR4 comprising an amino acid sequence having at least 95% identity to SEQ ID NO: 18 (FGQGTKLEIK), and a VH comprising a CDRH1 set forth in SEQ ID NO: 4 (GYTFTDYNMH), a CDRH2 set forth in SEQ ID NO: 5 (YVYPX5IGGTG), wherein X5is Y or S, a CDRH3 set forth in SEQ ID NO: 6 (RGYX10GIFDY), wherein X10 is D or E, a VH FR1 comprising an amino acid sequence having at least 95% identity to SEQ ID NO: 19 (X20VQLVQSGAEVKKPGASVKISCKAS), wherein X20is E or Q, a VH FR2 comprising an amino acid sequence having at least 95% identity to SEQ ID NO: 20 (WVRQAPGQGLEWIG), a VH FR3 comprising an amino acid sequence having at least 95% identity to SEQ ID NO: 21 (YNQKFKNRATLTVDTSTSTAYMELSSLRSEDTAVYYCTR), and a VH FR4 comprising an amino acid sequence having at least 95% identity to SEQ ID NO: 22 (WGQGTTLTVSS).

[0231] In certain aspects, the disclosure provides an anti-C2 antibody or antigen binding fragment thereof comprising a VL comprising the CDRL1 set forth in SEQ ID NO: 1 (XsTFTDIDDDMN), wherein X8is I or R, the CDRL3 set forth in SEQ ID NO: 3 (X9QSDNLPFT), wherein X9 is L or Q, and the VL FR3 comprising an amino acid sequence having at least 95% identity to SEQ ID NO: 17 (GVPSRFSXI8SGYGTDFTFHSSMQPEDXI9ATYYC), wherein Xi8is75FH13167949.1BPX-05925S or G; X19 is V or F, and a VH comprising the CDRH3 set forth in SEQ ID NO: 6 (RGYX10GIFDY), wherein X10 is D or E.

[0232] In some embodiments, the anti-C2 antibody or antigen binding fragment comprises a VL comprising a CDRL1 set forth in SEQ ID NO: 7 (ITFTDIDDDMN), a CDRL2 set forth in SEQ ID NO: 2, a CDRL3 set forth in SEQ ID NO: 9 (LQSDNLPFT), a VL FR1 set forth in SEQ ID NO: 23 (ETTVTQSPSSLSMSVGDRVTITC), a VL FR2 set forth in SEQ ID NO: 28 (WYQQKPGKPPKLLIS), a VL FR3 set forth in SEQ ID NO: 30 (GVPSRFSSSGYGTDFTFTISSMQPEDVATYYC), and a VL FR4 set forth in SEQ ID NO: 18, and a VH comprising a CDRH1 set forth in SEQ ID NO: 4, a CDRH2 set forth in SEQ ID NO: 11 (YVYPYIGGTG), a CDRH3 set forth in SEQ ID NO: 13 (RGYDGIFDY), a VH FR1 set forth in SEQ ID NO: 33 (EVQLVQSGAEVKKPGASVKISCKAS), a VH FR2 set forth in SEQ ID NO: 20, a VH FIG set forth in SEQ ID NO: 21, and a VH FR4 set forth in SEQ ID NO: 22.

[0233] In some embodiments, the anti-C2 antibody or antigen binding fragment comprises a VL comprising a CDRL1 set forth in SEQ ID NO: 7, a CDRL2 set forth in SEQ ID NO: 2, a CDRL3 set forth in SEQ ID NO: 9, a VL FR1 set forth in SEQ ID NO: 23, a VL FR2 set forth in SEQ ID NO: 28, a VL FI set forth in SEQ ID NO: 30, and a VL FR4 set forth in SEQ ID NO: 18, and a VH comprising a CDRH1 set forth in SEQ ID NO: 4, a CDRH2 set forth in SEQ ID NO: 11, a CDRH3 set forth in SEQ ID NO: 13, a VH FR1 set forth in SEQ ID NO: 34 (QVQLVQSGAEVKKPGASVKISCKAS), a VHFR2 set forth in SEQ ID NO: 20, a VH FIG set forth in SEQ ID NO: 21, and a VH FR4 set forth in SEQ ID NO: 22.

[0234] In some embodiments, the anti-C2 antibody or antigen binding fragment comprises a VL comprising a CDRL1 set forth in SEQ ID NO: 7, a CDRL2 set forth in SEQ ID NO: 2, a CDRL3 set forth in SEQ ID NO: 9, a VL FR1 set forth in SEQ ID NO: 24 (ETTVTQSPSSLSASVGDRVTITC), a VL FIG set forth in SEQ ID NO: 29 (WYQQKPGKAPKLLIS), a VL FR3 set forth in SEQ ID NO: 31 (GVPSRFSSSGYGTDFTFTISSMQPEDFATYYC), and a VL FR4 set forth in SEQ ID NO: 18, and a VH comprising a CDRH1 set forth in SEQ ID NO: 4, a CDRH2 set forth in SEQ ID NO: 11, a CDRH3 set forth in SEQ ID NO: 13, a VH FR1 set forth in SEQ ID NO: 33, a VH FIG set forth in SEQ ID NO: 20, a VH FR3 set forth in SEQ ID NO: 21, and a VH FR4 set forth in SEQ ID NO: 22.76FH13167949.1BPX-05925

[0235] In some embodiments, the anti-C2 antibody or antigen binding fragment comprises a VL comprising a CDRL1 set forth in SEQ ID NO: 8 (RTFTDIDDDMN), a CDRL2 set forth in SEQ ID NO: 2, a CDRL3 set forth in SEQ ID NO: 9, a VL FR1 set forth in SEQ ID NO: 24, a VL FR2 set forth in SEQ ID NO: 29, a VL FR3 set forth in SEQ ID NO: 32 (GVPSRFSGSGYGTDFTFTISSMQPEDFATYYC), and a VL FR4 set forth in SEQ ID NO: 18, and a VH comprising a CDRH1 set forth in SEQ ID NO: 4, a CDRH2 set forth in SEQ ID NO: 11, a CDRH3 set forth in SEQ ID NO: 13, a VH FR1 set forth in SEQ ID NO: 33, a VH FR2 set forth in SEQ ID NO: 20, a VH FR3 set forth in SEQ ID NO: 21, and a VH FR4 set forth in SEQ ID NO: 22.

[0236] In some embodiments, the anti-C2 antibody or antigen binding fragment comprises a VL comprising a CDRL1 set forth in SEQ ID NO: 8, a CDRL2 set forth in SEQ ID NO: 2, a CDRL3 set forth in SEQ ID NO: 9, a VL FR1 set forth in SEQ ID NO: 23, a VL FR2 set forth in SEQ ID NO: 28, a VL FIG set forth in SEQ ID NO: 30, and a VL FR4 set forth in SEQ ID NO: 18, and a VH comprising a CDRH1 set forth in SEQ ID NO: 4, a CDRH2 set forth in SEQ ID NO: 11, a CDRH3 set forth in SEQ ID NO: 13, a VH FR1 set forth in SEQ ID NO: 33, a VH FR2 set forth in SEQ ID NO: 20, a VH FR3 set forth in SEQ ID NO: 21, and a VH FR4 set forth in SEQ ID NO: 22.

[0237] In some embodiments, the anti-C2 antibody or antigen binding fragment comprises a VL comprising a CDRL1 set forth in SEQ ID NO: 8, a CDRL2 set forth in SEQ ID NO: 2, a CDRL3 set forth in SEQ ID NO: 9, a VL FR1 set forth in SEQ ID NO: 24, a VL FR2 set forth in SEQ ID NO: 29, a VL FIG set forth in SEQ ID NO: 32, and a VL FR4 set forth in SEQ ID NO: 18, and a VH comprising a CDRH1 set forth in SEQ ID NO: 4, a CDRH2 set forth in SEQ ID NO: 11, a CDRH3 set forth in SEQ ID NO: 14, a VH FR1 set forth in SEQ ID NO: 33, a VH FIG set forth in SEQ ID NO: 20, a VH FR3 set forth in SEQ ID NO: 21, and a VH FR4 set forth in SEQ ID NO: 22.

[0238] In some embodiments, the anti-C2 antibody or antigen binding fragment comprises a VL comprising a CDRL1 set forth in SEQ ID NO: 8, a CDRL2 set forth in SEQ ID NO: 2, a CDRL3 set forth in SEQ ID NO: 9, a VL FR1 set forth in SEQ ID NO: 24, a VL FIG set forth in SEQ ID NO: 29, a VL FIG set forth in SEQ ID NO: 32, and a VL FR4 set forth in SEQ ID NO: 18, and a VH comprising a CDRH1 set forth in SEQ ID NO: 4, a CDRH2 set forth in SEQ ID NO: 12, a CDRH3 set forth in SEQ ID NO: 13, a VH FR1 set forth in SEQ ID NO: 33, a VH FIG set forth77FH13167949.1BPX-05925 in SEQ ID NO: 20, a VH FR3 set forth in SEQ ID NO: 21, and a VH FR4 set forth in SEQ ID NO: 22.

[0239] In some embodiments, the anti-C2 antibody or antigen binding fragment comprises a VL comprising a CDRL1 set forth in SEQ ID NO: 8, a CDRL2 set forth in SEQ ID NO: 2, a CDRL3 set forth in SEQ ID NO: 9, a VL FR1 set forth in SEQ ID NO: 24, a VL FR2 set forth in SEQ ID NO: 29, a VL FR3 set forth in SEQ ID NO: 32, and a VL FR4 set forth in SEQ ID NO: 18, and a VH comprising a CDRH1 set forth in SEQ ID NO: 4, a CDRH2 set forth in SEQ ID NO: 12, a CDRH3 set forth in SEQ ID NO: 14, a VH FR1 set forth in SEQ ID NO: 33, a VH FR2 set forth in SEQ ID NO: 20, a VH FR3 set forth in SEQ ID NO: 21, and a VH FR4 set forth in SEQ ID NO: 22.

[0240] In some embodiments, the anti-C2 antibody or antigen binding fragment comprises a VL comprising a CDRL1 set forth in SEQ ID NO: 8, a CDRL2 set forth in SEQ ID NO: 2, a CDRL3 set forth in SEQ ID NO: 10, a VL FR1 set forth in SEQ ID NO: 24, a VL FR2 set forth in SEQ ID NO: 29, a VL FR3 set forth in SEQ ID NO: 32, and a VL FR4 set forth in SEQ ID NO: 18, and a VH comprising a CDRH1 set forth in SEQ ID NO: 4, a CDRH2 set forth in SEQ ID NO: 12, a CDRH3 set forth in SEQ ID NO: 14, a VH FR1 set forth in SEQ ID NO: 33, a VH FR2 set forth in SEQ ID NO: 20, a VH FR3 set forth in SEQ ID NO: 21, and a VH FR4 set forth in SEQ ID NO: 22.

[0241] In some embodiments, the anti-C2 antibody or antigen binding fragment comprises a VL comprising a the CDRL1 set forth in SEQ ID NO: 7, a CDRL2 set forth in SEQ ID NO: 2, a CDRL3 set forth in SEQ ID NO: 9, a VL FR1 set forth in SEQ ID NO: 24, a VL FR2 set forth in SEQ ID NO: 29, a VL FR3 set forth in SEQ ID NO: 32, and a VL FR4 set forth in SEQ ID NO: 18, and a VH comprising a CDRH1 set forth in SEQ ID NO: 4, a CDRH2 set forth in SEQ ID NO: 12, a CDRH3 set forth in SEQ ID NO: 14, a VH FR1 set forth in SEQ ID NO: 33, a VH FR2 set forth in SEQ ID NO: 20, a VH FR3 set forth in SEQ ID NO: 21, and VH FR4 set forth in SEQ ID NO: 22.

[0242] In some embodiments, the anti-C2 antibody or antigen binding fragment comprises a VL comprising a CDRL1 set forth in SEQ ID NO: 7, a CDRL2 set forth in SEQ ID NO: 2, a CDRL3 set forth in SEQ ID NO: 9, a VL FR1 set forth in SEQ ID NO: 23, a VL FR2 set forth in SEQ ID NO: 28, a VL FI set forth in SEQ ID NO: 30, and a VL FR4 set forth in SEQ ID NO: 18, and a VH comprising a CDRH1 set forth in SEQ ID NO: 4, a CDRH2 set forth in SEQ ID NO: 11,78FH13167949.1BPX-05925 a CDRH3 set forth in SEQ ID NO: 14, a VH FR1 set forth in SEQ ID NO: 33, a VH FR2 set forth in SEQ ID NO: 20, a VH FR3 set forth in SEQ ID NO: 21, and a VH FR4 set forth in SEQ ID NO: 22.

[0243] In some embodiments, the anti-C2 antibody or antigen binding fragment comprises a VL comprising a the CDRL1 set forth in SEQ ID NO: 8, a CDRL2 set forth in SEQ ID NO: 2, a CDRL3 set forth in SEQ ID NO: 9, a VL FR1 set forth in SEQ ID NO: 23, a VL FR2 set forth in SEQ ID NO: 28, a VL FIG set forth in SEQ ID NO: 30, and a VL FR4 set forth in SEQ ID NO: 18, and a VH comprising a CDRH1 set forth in SEQ ID NO: 4, a CDRH2 set forth in SEQ ID NO: 11, a CDRH3 set forth in SEQ ID NO: 14, a VH FR1 set forth in SEQ ID NO: 33, a VH FR2 set forth in SEQ ID NO: 20, a VH FR3 set forth in SEQ ID NO: 21, and a VH FR4 set forth in SEQ ID NO: 22.

[0244] In some embodiments, the anti-C2 antibody or antigen binding fragment comprises a VL comprising a CDRL1 set forth in SEQ ID NO: 7, a CDRL2 set forth in SEQ ID NO: 2, a CDRL3 set forth in SEQ ID NO: 9, a VL FR1 set forth in SEQ ID NO: 25, a VL FR2 set forth in SEQ ID NO: 28, a VL FI set forth in SEQ ID NO: 30, and a VL FR4 set forth in SEQ ID NO: 18, and a VH comprising a CDRH1 set forth in SEQ ID NO: 4, a CDRH2 set forth in SEQ ID NO: 11, a CDRH3 set forth in SEQ ID NO: 14, a VH FR1 set forth in SEQ ID NO: 33, a VH FIG set forth in SEQ ID NO: 20, a VH FR3 set forth in SEQ ID NO: 21, and a VH FR4 set forth in SEQ ID NO: 22.

[0245] In some embodiments, the anti-C2 antibody or antigen binding fragment comprises a VL comprising a CDRL1 set forth in SEQ ID NO: 7, a CDRL2 set forth in SEQ ID NO: 2, a CDRL3 set forth in SEQ ID NO: 9, a VL FR1 set forth in SEQ ID NO: 26, a the VL FIG set forth in SEQ ID NO: 28, a VL FIG set forth in SEQ ID NO: 30, and a VL FR4 set forth in SEQ ID NO: 18, and a VH comprising a CDRH1 set forth in SEQ ID NO: 4, a CDRH2 set forth in SEQ ID NO: 11, a CDRH3 set forth in SEQ ID NO: 14, a VH FR1 set forth in SEQ ID NO: 33, a VH FIG set forth in SEQ ID NO: 20, a VH FIG set forth in SEQ ID NO: 21, and a VH FR4 set forth in SEQ ID NO: 22.

[0246] In some embodiments, the anti-C2 antibody or antigen binding fragment comprises a VL comprising a CDRL1 set forth in SEQ ID NO: 7, a CDRL2 set forth in SEQ ID NO: 2, a CDRL3 set forth in SEQ ID NO: 9, a VL FR1 set forth in SEQ ID NO: 27, a VL FIG set forth in SEQ ID NO: 28, a VL FIG set forth in SEQ ID NO: 30, and a VL FR4 set forth in SEQ ID NO: 18,79FH13167949.1BPX-05925 and a VH comprising a CDRH1 set forth in SEQ ID NO: 4, a CDRH2 set forth in SEQ ID NO: 11, a CDRH3 set forth in SEQ ID NO: 14, a VH FR1 set forth in SEQ ID NO: 33, a VH FR2 set forth in SEQ ID NO: 20, a VH FR3 set forth in SEQ ID NO: 21, and a VH FR4 set forth in SEQ ID NO: 22.

[0247] In some embodiments, the anti-C2 antibody or antigen binding fragment comprises a VL comprising a CDRL1 set forth in SEQ ID NO: 7, a CDRL2 set forth in SEQ ID NO: 2, a CDRL3 set forth in SEQ ID NO: 9, a VL FR1 set forth in SEQ ID NO: 23, a VL FR2 set forth in SEQ ID NO: 28, a VL FIG set forth in SEQ ID NO: 30, and a VL FR4 set forth in SEQ ID NO: 18, and a VH comprising a CDRH1 set forth in SEQ ID NO: 4, a CDRH2 set forth in SEQ ID NO: 12, a CDRH3 set forth in SEQ ID NO: 13, a VH FR1 set forth in SEQ ID NO: 33, a VH FR2 set forth in SEQ ID NO: 20, a VH FR3 set forth in SEQ ID NO: 21, and a VH FR4 set forth in SEQ ID NO: 22.

[0248] In some embodiments, the anti-C2 antibody or antigen binding fragment comprises a VL comprising a the CDRL1 set forth in SEQ ID NO: 7, a CDRL2 set forth in SEQ ID NO: 2, a CDRL3 set forth in SEQ ID NO: 9, a VL FR1 set forth in SEQ ID NO: 23, a VL FR2 set forth in SEQ ID NO: 28, a VL FI set forth in SEQ ID NO: 30, and a VL FR4 set forth in SEQ ID NO: 18, and a VH comprising a CDRH1 set forth in SEQ ID NO: 4, a CDRH2 set forth in SEQ ID NO: 12, a CDRH3 set forth in SEQ ID NO: 14, a VH FR1 set forth in SEQ ID NO: 33, a VH FIG set forth in SEQ ID NO: 20, a VH FR3 set forth in SEQ ID NO: 21, and a VH FR4 set forth in SEQ ID NO: 22.

[0249] In some embodiments, the anti-C2 antibody or antigen binding fragment comprises a VL comprising a CDRL1 set forth in SEQ ID NO: 8, a CDRL2 set forth in SEQ ID NO: 2, a CDRL3 set forth in SEQ ID NO: 9, a VL FR1 set forth in SEQ ID NO: 23, a VL FIG set forth in SEQ ID NO: 28, a VL FIG set forth in SEQ ID NO: 30, and a VL FR4 set forth in SEQ ID NO: 18, and a VH comprising a CDRH1 set forth in SEQ ID NO: 4, a the CDRH2 set forth in SEQ ID NO: 12, a CDRH3 set forth in SEQ ID NO: 14, a VH FR1 set forth in SEQ ID NO: 33, a VH FIG set forth in SEQ ID NO: 20, a VH FIG set forth in SEQ ID NO: 21, and a VH FR4 set forth in SEQ ID NO: 22.

[0250] In some embodiments, the anti-C2 antibody or antigen binding fragment comprises a VL comprising a the CDRL1 set forth in SEQ ID NO: 8 a CDRL2 set forth in SEQ ID NO: 2, a CDRL3 set forth in SEQ ID NO: 9, a VL FR1 set forth in SEQ ID NO: 24, a VL FIG set forth in80FH13167949.1BPX-05925SEQ ID NO: 28, a VL FR3 set forth in SEQ ID NO: 30, and a VL FR4 set forth in SEQ ID NO: 18, and a VH comprising a CDRH1 set forth in SEQ ID NO: 4, a CDRH2 set forth in SEQ ID NO: 12, a CDRH3 set forth in SEQ ID NO: 14, a VH FR1 set forth in SEQ ID NO: 33, a VH FR2 set forth in SEQ ID NO: 20, a VH FR3 set forth in SEQ ID NO: 21, and a VH FR4 set forth in SEQ ID NO: 22.

[0251] In some embodiments, the anti-C2 antibody or antigen binding fragment comprises a VL comprising a CDRL1 set forth in SEQ ID NO: 7, a CDRL2 set forth in SEQ ID NO: 2, a CDRL3 set forth in SEQ ID NO: 9, a the VL FR1 set forth in SEQ ID NO: 24, a the VL FR2 set forth in SEQ ID NO: 28, a VL FIG set forth in SEQ ID NO: 30, and a VL FR4 set forth in SEQ ID NO: 18, and a VH comprising a CDRH1 set forth in SEQ ID NO: 4, a CDRH2 set forth in SEQ ID NO: 12, CDRH3 set forth in SEQ ID NO: 14, a VH FR1 set forth in SEQ ID NO: 33, a VH FR2 set forth in SEQ ID NO: 20, a VH FI set forth in SEQ ID NO: 21, and a VH FR4 set forth in SEQ ID NO: 22.

[0252] In some embodiments, the anti-C2 antibody or antigen binding fragment comprises a VL comprising a CDRL1 set forth in SEQ ID NO: 8, a CDRL2 set forth in SEQ ID NO: 2, a CDRL3 set forth in SEQ ID NO: 10, a VL FR1 set forth in SEQ ID NO: 24, a VL FIG set forth in SEQ ID NO: 28, a VL FIG set forth in SEQ ID NO: 30, and a VL FR4 set forth in SEQ ID NO: 18, and a VH comprising a CDRH1 set forth in SEQ ID NO: 4, a CDRH2 set forth in SEQ ID NO: 12, a CDRH3 set forth in SEQ ID NO: 14, a VH FR1 set forth in SEQ ID NO: 33, a VH FIG set forth in SEQ ID NO: 20, a VH FR3 set forth in SEQ ID NO: 21, and a VH FR4 set forth in SEQ ID NO: 22.

[0253] In some embodiments, the anti-C2 antibody or antigen binding fragment comprises a VL comprising a CDRL1 set forth in SEQ ID NO: 7, a CDRL2 set forth in SEQ ID NO: 2, a CDRL3 set forth in SEQ ID NO: 10, a VL FR1 set forth in SEQ ID NO: 24, a VL FIG set forth in SEQ ID NO: 28, a VL FIG set forth in SEQ ID NO: 30, and a VL FR4 set forth in SEQ ID NO: 18, and a VH comprising a CDRH1 set forth in SEQ ID NO: 4, a CDRH2 set forth in SEQ ID NO: 12, a CDRH3 set forth in SEQ ID NO: 14, a VH FR1 set forth in SEQ ID NO: 33, a VH FIG set forth in SEQ ID NO: 20, a VH FR3 set forth in SEQ ID NO: 21, and a VH FR4 set forth in SEQ ID NO: 22.

[0254] In some embodiments, the anti-C2 antibody or antigen binding fragment comprises a VL comprising a CDRL1 set forth in SEQ ID NO: 7, a CDRL2 set forth in SEQ ID NO: 2, a81FH13167949.1BPX-05925CDRL3 set forth in SEQ ID NO: 9, a VL FR1 set forth in SEQ ID NO: 24, a VL FR2 set forth in SEQ ID NO: 28, a VL FR3 set forth in SEQ ID NO: 30, and a VL FR4 set forth in SEQ ID NO: 18, and a VH comprising a CDRH1 set forth in SEQ ID NO: 4, a CDRH2 set forth in SEQ ID NO: 11, a CDRH3 set forth in SEQ ID NO: 13, a VH FR1 set forth in SEQ ID NO: 33, a VH FR2 set forth in SEQ ID NO: 20, a VH FR3 set forth in SEQ ID NO: 21, and a VH FR4 set forth in SEQ ID NO: 22.

[0255] In some embodiments, the anti-C2 antibody or antigen binding fragment comprises a VL comprising a CDRL1 set forth in SEQ ID NO: 7, a CDRL2 set forth in SEQ ID NO: 2, a CDRL3 set forth in SEQ ID NO: 9, a VL FR1 set forth in SEQ ID NO: 24, a VL FR2 set forth in SEQ ID NO: 28, a VL FIG set forth in SEQ ID NO: 30, and a VL FR4 set forth in SEQ ID NO: 18, and a VH comprising a CDRH1 set forth in SEQ ID NO: 4, a CDRH2 set forth in SEQ ID NO: 12, a CDRH3 set forth in SEQ ID NO: 13, a VH FR1 set forth in SEQ ID NO: 33, a VH FR2 set forth in SEQ ID NO: 20, a VH FR3 set forth in SEQ ID NO: 21, and a VH FR4 set forth in SEQ ID NO: 22.

[0256] In some embodiments, the anti-C2 antibody or antigen binding fragment comprises a VL comprising a CDRL1 set forth in SEQ ID NO: 7, a CDRL2 set forth in SEQ ID NO: 2, a CDRL3 set forth in SEQ ID NO: 10, a VL FR1 set forth in SEQ ID NO: 24, a VL FR2 set forth in SEQ ID NO: 28, a VL FI set forth in SEQ ID NO: 30, and a VL FR4 set forth in SEQ ID NO: 18, and a VH comprising a CDRH1 set forth in SEQ ID NO: 4, a CDRH2 set forth in SEQ ID NO: 12, a CDRH3 set forth in SEQ ID NO: 13, a VH FR1 set forth in SEQ ID NO: 33, a VH FIG set forth in SEQ ID NO: 20, a VH FR3 set forth in SEQ ID NO: 21, and a VH FR4 set forth in SEQ ID NO: 22.

[0257] In some embodiments, the anti-C2 antibody or antigen binding fragment comprises a VL comprising a CDRL1 set forth in SEQ ID NO: 8, a CDRL2 set forth in SEQ ID NO: 2, a CDRL3 set forth in SEQ ID NO: 190, a VL FR1 set forth in SEQ ID NO: 24, a VL FIG set forth in SEQ ID NO: 28, a VL FIG set forth in SEQ ID NO: 192, and a VL FR4 set forth in SEQ ID NO: 18, and a VH comprising a CDRH1 set forth in SEQ ID NO: 4, a CDRH2 set forth in SEQ ID NO: 12, a CDRH3 set forth in SEQ ID NO: 14, a VH FR1 set forth in SEQ ID NO: 33, a VH FIG set forth in SEQ ID NO: 20, a VH FIG set forth in SEQ ID NO: 21, and a VH FR4 set forth in SEQ ID NO: 22.82FH13167949.1BPX-05925

[0258] In some embodiments, the anti-C2 antibody or antigen binding fragment comprises a VL comprising a CDRL1 set forth in SEQ ID NO: 188, a CDRL2 set forth in SEQ ID NO: 2, a CDRL3 set forth in SEQ ID NO: 190, a VL FR1 set forth in SEQ ID NO: 24, a VL FR2 set forth in SEQ ID NO: 28, a VL FR3 set forth in SEQ ID NO: 192, and a VL FR4 set forth in SEQ ID NO: 18, and a VH comprising a CDRH1 set forth in SEQ ID NO: 4, a CDRH2 set forth in SEQ ID NO: 12, a CDRH3 set forth in SEQ ID NO: 14, a VH FR1 set forth in SEQ ID NO: 33, a VH FR2 set forth in SEQ ID NO: 20, a VH FIG set forth in SEQ ID NO: 21, and a VH FR4 set forth in SEQ ID NO: 22.

[0259] In some embodiments, the anti-C2 antibody or antigen binding fragment comprises a VL comprising a CDRL1 set forth in SEQ ID NO: 8, a CDRL2 set forth in SEQ ID NO: 2, a CDRL3 set forth in SEQ ID NO: 190, a VL FR1 set forth in SEQ ID NO: 24, a VL FR2 set forth in SEQ ID NO: 28, a VL FI set forth in SEQ ID NO: 192, and a VL FR4 set forth in SEQ ID NO: 18, and a VH comprising a CDRH1 set forth in SEQ ID NO: 4, a CDRH2 set forth in SEQ ID NO: 12, a CDRH3 set forth in SEQ ID NO: 191, a VH FR1 set forth in SEQ ID NO: 33, a VH FIG set forth in SEQ ID NO: 20, a VH FIG set forth in SEQ ID NO: 21, and a VH FR4 set forth in SEQ ID NO: 22.

[0260] In some embodiments, the light chain variable region comprises a leader sequence. In some embodiments, the leader sequence has a sequence set forth in SEQ ID NO: 169. In some embodiments, the leader sequence has a sequence set forth in SEQ ID NO: 170.

[0261] In some embodiments, the heavy chain variable region comprises a leader sequence. In some embodiments, the leader sequence has a sequence set forth in SEQ ID NO: 169. In some embodiments, the leader sequence has a sequence set forth in SEQ ID NO: 170. In some embodiments, when the heavy chain variable region comprises a leader sequence, the leader sequence is the same as the leader sequence of the light chain variable region.

[0262] In some embodiments, the anti-C2 antibody or antigen binding fragment thereof comprises a histidine at amino acid position L26, amino acid position L67, amino acid position L93, and / or amino acid position H97 (numbering according to Kabat). In some embodiments, the anti-C2 antibody or antigen binding fragment thereof comprises a histidine at amino acid position L26, amino acid position L67, amino acid position L93, amino acid position H97, or any combination thereof (numbering according to Kabat).83FH13167949.1BPX-05925Heavy chain and Light chain constant region

[0263] In some embodiments, the antibody, or antigen binding fragment thereof, comprises a heavy chain constant region. In some embodiments, the heavy chain constant region is an IgG constant region. In some embodiments, the IgG constant region is a wild-type IgG constant region. In some embodiments, the IgG constant region comprises at least one mutation relative to a wildtype IgG constant region. In some embodiments, the IgG constant region is an IgGl, IgG2, IgG3, or IgG4 constant region. In some embodiments, the IgG constant region is an IgGl constant region. In some embodiments, the IgGl constant region is a wild-type IgGl constant region. In some embodiments, the IgGl constant region is a wild-type human IgGl constant region. In some embodiments, the IgGl constant region comprises L234A and L235A amino acid substitutions relative to a wild-type human IgGl constant region, according to EU numbering. In some embodiments, the IgG constant region is an IgGl constant region comprising M428L and N434S amino acid substitutions relative to a wild-type human IgGl constant region, according to EU numbering. In some embodiments, the IgG constant region is an IgGl constant region comprising L234A and L235A amino acid substitutions and M428L and N434S amino acid substitutions relative to a wild-type IgGl . In some embodiments, the IgG constant region is an IgG4 constant region. In some embodiments, the IgG4 constant region is a wild-type IgG4 constant region. In some embodiments, the IgGl constant region comprises at least one amino acid substitution selected from: L234A, L235A, L235E, H268Q, V309L, A330S, P331S, and any combination thereof, relative to a wild-type human IgGl constant region, according to EU numbering. In some embodiments, the IgGl constant region comprises at least one amino acid substitution selected from: M252Y, S264T, T256E, M428L, N434S, and any combination thereof, relative to a wild-type human IgGl constant region, according to EU numbering. In some embodiments, the IgGl constant region comprises an N297A, N297Q or N297G amino acid substitution relative to a wild-type human IgGl constant region, according to EU numbering.

[0264] In some embodiments, the IgGl constant region comprises an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to an amino acid sequence selected from SEQ ID Nos: 171-176.

[0265] In some embodiments, the IgGl constant region comprises an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to the84FH13167949.1BPX-05925 amino acid sequence of SEQ ID NO: 171. In some embodiments, the IgGl constant region comprises the amino acid sequence of SEQ ID NO: 171.

[0266] In some embodiments, the IgGl constant region comprises an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to the amino acid sequence of SEQ ID NO: 172. In some embodiments, the IgGl constant region comprises the amino acid sequence of SEQ ID NO: 172.

[0267] In some embodiments, the IgGl constant region comprises an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to the amino acid sequence of SEQ ID NO: 173. In some embodiments, the IgGl constant region comprises the amino acid sequence of SEQ ID NO: 173.

[0268] In some embodiments, the IgGl constant region comprises an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to the amino acid sequence of SEQ ID NO: 174. In some embodiments, the IgGl constant region comprises the amino acid sequence of SEQ ID NO: 174.

[0269] In some embodiments, the IgGl constant region comprises an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to the amino acid sequence of SEQ ID NO: 175. In some embodiments, the IgGl constant region comprises the amino acid sequence of SEQ ID NO: 175.

[0270] In some embodiments, the IgGl constant region comprises an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to the amino acid sequence of SEQ ID NO: 176. In some embodiments, the IgGl constant region comprises the amino acid sequence of SEQ ID NO: 176.

[0271] In some embodiments, the IgG2 constant region is a wild-type human IgG2 constant region. In some embodiments, the IgG2 constant region comprises at least one amino acid substitution selected from: H268Q, V309L, A330S, P331S, V234A, G237A, P238S, H268A, and any combination thereof, relative to a wild-type human IgG2 constant region, according to EU numbering.

[0272] In some embodiments, the IgG2 constant region comprises an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to the amino acid sequence of SEQ ID NO: 177. In some embodiments, the IgG2 constant region comprises the amino acid sequence of SEQ ID NO: 177.85FH13167949.1BPX-05925

[0273] In some embodiments, the IgG3 constant region is a wild-type human IgG3 constant region. In some embodiments, the IgG3 constant region comprises an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to the amino acid sequence of SEQ ID NO: 178. In some embodiments, the IgG3 constant region comprises the amino acid sequence of SEQ ID NO: 178.

[0274] In some embodiments, the IgG4 constant region is a wild-type human IgG4 constant region. In some embodiments, the IgG4 constant region comprises an F234A and / or an L235A amino acid substitution relative to a wild-type human IgG4 constant region, according to EU numbering. In some embodiments, the IgG4 constant region comprises an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to the amino acid sequence of SEQ ID NO: 179. In some embodiments, the IgG4 constant region comprises the amino acid sequence of SEQ ID NO: 179.

[0275] In some embodiments, the anti-C2 antibody, or antigen binding fragment thereof, comprises any one of the VH sequences herein described and any one of the IgG constant regions as set forth in SEQ ID NOs: 171-179.

[0276] In some embodiments, the anti-C2 antibody, or antigen binding fragment thereof, comprises any one of the VH sequences herein described and the IgG constant region is set forth in any one of SEQ ID NOs: 171-175 as shown in Table 11. In some embodiments, the heavy chain constant region is set forth in SEQ ID NO: 171, wherein X21 is K or R (allotype), X22 is L or A, X23 is L or A, X24 is M or Y, X25 is S or T, X26 is T or E, X27 is E or D (allotype), X28 is M or L (allotype), X29 is M or L, X30 is N or S, X31 is A or G (allotype), X32 is G or E (seq of isoform 2), X33 is K or L (seq of isoform 2). In some embodiments, the heavy chain constant region is set forth in SEQ ID NO: 172, wherein X21 is K or R (allotype), X27 is E or D (allotype), X28 is M or L (allotype), X31 is A or G (allotype), X32 is G or E (seq of isoform 2), X33 is K or L (seq of isoform 2). In some embodiments, the heavy chain constant region is set forth in SEQ ID NO: 173 wherein X21 is K or R (allotype), X27 is E or D (allotype), X28 is M or L (allotype), X31 is A or G (allotype), X32 is G or E (seq of isoform 2), X33 is K or L (seq of isoform 2). In some embodiments, the heavy chain constant region is set forth in SEQ ID NO: 174 where X21 is K or R (allotype), X27 is E or D (allotype), X28 is M or L (allotype), X31 is A or G (allotype), X32 is G or E (seq of isoform 2), X33 is K or L (seq of isoform 2). In some embodiments, the heavy chain constant region is set forth in86FH13167949.1BPX-05925SEQ ID NO: 175 where X21 is K or R (allotype), X27 is E or D (allotype), X28 is M or L (allotype), X31 is A or G (allotype), X32 is G or E (seq of isoform 2), X33 is K or L (seq of isoform 2).

[0277] In some embodiments, the anti-C2 antibody, or antigen binding fragment thereof, comprises any one of the VH sequences herein described and the IgG constant region is set forth in SEQ ID NO: 176 as shown in Table 11.

[0278] In some embodiments, the antibody, or antigen binding fragment thereof, comprises a light chain constant region. In some embodiments, the light chain constant region is a kappa light chain. In some embodiments, the light chain constant region is a lambda light chain.

[0279] In some embodiments, the kappa light chain comprises an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to the amino acid sequence of SEQ ID NO: 180. In some embodiments, the light chain constant region is set forth in SEQ ID NO: 180.

[0280] In some embodiments, the lambda light chain comprises an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to the amino acid sequence of SEQ ID NO: 181. In some embodiments, the light chain constant region is set forth in SEQ ID NO: 181.

[0281] In some embodiments, the anti-C2 antibody, or antigen binding fragment thereof, comprises any one of the VL sequences herein described and the light chain constant region as set forth in SEQ ID NO: 180. In some embodiments, the anti-C2 antibody, or antigen binding fragment thereof, comprises any one of the VL sequences herein described and the light chain constant region as set forth in SEQ ID NO: 181.

[0282] In some embodiments, the anti-C2 antibody, or antigen binding fragment thereof, comprises any one of the VH sequences herein described, the IgG constant region is set forth in SEQ ID NO: 176, any one of the VL sequences herein described, and the light chain constant region as set forth in SEQ ID NO: 180, each as shown in Table 11.

[0283] In some embodiments, the anti-C2 antibody, or antigen binding fragment thereof, comprises a heavy chain (HC) comprising an amino acid sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 53.

[0284] In some embodiments, the anti-C2 antibody, or antigen binding fragment thereof, comprises a heavy chain (HC) comprising an amino acid sequence at least 80%, 81%, 82%, 83%,87FH13167949.1BPX-0592584%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 54.

[0285] In some embodiments, the anti-C2 antibody, or antigen binding fragment thereof, comprises a heavy chain (HC) comprising an amino acid sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 55.

[0286] In some embodiments, the anti-C2 antibody, or antigen binding fragment thereof, comprises a heavy chain (HC) comprising an amino acid sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 56.

[0287] In some embodiments, the anti-C2 antibody, or antigen binding fragment thereof, comprises a heavy chain (HC) comprising an amino acid sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 57.

[0288] In some embodiments, the anti-C2 antibody, or antigen binding fragment thereof, comprises a heavy chain (HC) comprising an amino acid sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 204.

[0289] In some embodiments, the anti-C2 antibody, or antigen binding fragment thereof, comprises a light chain (LC) comprising an amino acid sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 58.

[0290] In some embodiments, the anti-C2 antibody, or antigen binding fragment thereof, comprises a light chain (LC) comprising an amino acid sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 59.

[0291] In some embodiments, the anti-C2 antibody, or antigen binding fragment thereof, comprises a light chain (LC) comprising an amino acid sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 60.88FH13167949.1BPX-05925

[0292] In some embodiments, the anti-C2 antibody, or antigen binding fragment thereof, comprises a light chain (LC) comprising an amino acid sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 61.

[0293] In some embodiments, the anti-C2 antibody, or antigen binding fragment thereof, comprises a light chain (LC) comprising an amino acid sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 62.

[0294] In some embodiments, the anti-C2 antibody, or antigen binding fragment thereof, comprises a light chain (LC) comprising an amino acid sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 63.

[0295] In some embodiments, the anti-C2 antibody, or antigen binding fragment thereof, comprises a light chain (LC) comprising an amino acid sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 64.

[0296] In some embodiments, the anti-C2 antibody, or antigen binding fragment thereof, comprises a light chain (LC) comprising an amino acid sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 65.

[0297] In some embodiments, the anti-C2 antibody, or antigen binding fragment thereof, comprises a light chain (LC) comprising an amino acid sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 66.

[0298] In some embodiments, the anti-C2 antibody, or antigen binding fragment thereof, comprises a light chain (LC) comprising an amino acid sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 67.

[0299] In some embodiments, the anti-C2 antibody, or antigen binding fragment thereof, comprises a light chain (LC) comprising an amino acid sequence at least 80%, 81%, 82%, 83%,89FH13167949.1BPX-0592584%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 68.

[0300] In some embodiments, the anti-C2 antibody, or antigen binding fragment thereof, comprises a light chain (LC) comprising an amino acid sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 69.

[0301] In some embodiments, the anti-C2 antibody, or antigen binding fragment thereof, comprises a light chain (LC) comprising an amino acid sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 70.

[0302] In some embodiments, the anti-C2 antibody, or antigen binding fragment thereof, comprises a light chain (LC) comprising an amino acid sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 205.

[0303] In some embodiments, the anti-C2 antibody, or antigen binding fragment thereof, comprises a light chain (LC) comprising an amino acid sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 206.

[0304] In some embodiments, the anti-C2 antibody, or antigen binding fragment thereof, comprises a light chain (LC) comprising an amino acid sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 207.

[0305] In some embodiments, the anti-C2 antibody, or antigen binding fragment thereof, comprises a light chain (LC) comprising an amino acid sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 208.

[0306] In some embodiments, the anti-C2 antibody, or antigen binding fragment thereof, comprises a light chain (LC) comprising an amino acid sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 209.90FH13167949.1BPX-05925

[0307] In some embodiments, the anti-C2 antibody, or antigen binding fragment thereof, comprises a light chain (LC) comprising an amino acid sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 210.

[0308] In some embodiments, the anti-C2 antibody, or antigen binding fragment thereof, comprises a light chain (LC) comprising an amino acid sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 211.

[0309] In some embodiments, the anti-C2 antibody, or antigen binding fragment thereof, comprises a light chain (LC) comprising an amino acid sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 212.

[0310] In some embodiments, the anti-C2 antibody, or antigen binding fragment thereof, comprises a light chain (LC) comprising an amino acid sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 213.

[0311] In some embodiments, the antibody, or antigen binding fragment thereof, comprises a heavy chain sequence and a light chain sequence comprising amino acid sequences having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequences selected from: SEQ ID NOs: 53 and 58, respectively; SEQ ID NOs: 53 and 70, respectively; SEQ ID NOs: 53 and 67, respectively; SEQ ID NOs: 53 and 66, respectively; SEQ ID NOs: 53 and 63, respectively; SEQ ID NOs: 54 and 58, respectively; SEQ ID NOs: 54 and 66, respectively; SEQ ID NOs: 54 and 59, respectively; SEQ ID NOs: 54 and 60, respectively; SEQ ID NOs: 54 and 61, respectively; SEQ ID NOs: 54 and 67, respectively; SEQ ID NOs: 55 and 58, respectively; SEQ ID NOs: 55 and 63, respectively; SEQ ID NOs: 55 and 65, respectively; SEQ ID NOs: 55 and 67, respectively; SEQ ID NOs: 56 and 67, respectively; SEQ ID NOs: 56 and 68, respectively; SEQ ID NOs: 56 and 69, respectively; SEQ ID NOs: 56 and 58, respectively; SEQ ID NOs: 56 and 66, respectively; SEQ ID NOs: 56 and 62, respectively; SEQ ID NOs: 56 and 63, respectively; SEQ ID NOs: 56 and 64, respectively; SEQ ID NOs: 56 and 65, respectively; and SEQ ID NOs: 57 and 58, respectively.91FH13167949.1BPX-05925

[0312] In some embodiments, the antibody, or antigen binding fragment thereof, comprises a heavy chain sequence and a light chain sequence comprising amino acid sequences having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequences selected from: SEQ ID NOs: 53 and 58, respectively; SEQ ID NOs: 53 and 70, respectively; SEQ ID NOs: 53 and 67, respectively; SEQ ID NOs: 53 and 66, respectively; SEQ ID NOs: 53 and 63, respectively; SEQ ID NOs: 54 and 58, respectively; SEQ ID NOs: 54 and 66, respectively; SEQ ID NOs: 54 and 59, respectively; SEQ ID NOs: 54 and 60, respectively; SEQ ID NOs: 54 and 61, respectively; SEQ ID NOs: 54 and 67, respectively; SEQ ID NOs: 55 and 58, respectively; SEQ ID NOs: 55 and 63, respectively; SEQ ID NOs: 55 and 65, respectively; SEQ ID NOs: 55 and 67, respectively; SEQ ID NOs: 56 and 67, respectively; SEQ ID NOs: 56 and 68, respectively; SEQ ID NOs: 56 and 69, respectively; SEQ ID NOs: 56 and 58, respectively; SEQ ID NOs: 56 and 66, respectively; SEQ ID NOs: 56 and 62, respectively; SEQ ID NOs: 56 and 63, respectively; SEQ ID NOs: 56 and 64, respectively; SEQ ID NOs: 56 and 65, respectively; SEQ ID NOs: 57 and 58, respectively; SEQ ID NOs: 56 and 205, respectively; SEQ ID NOs: 56 and 206, respectively; SEQ ID NOs: 56 and 207, respectively; SEQ ID NOs: 204 and 66, respectively; SEQ ID NOs: 204 and 205, respectively; SEQ ID NOs: 56 and 208, respectively; SEQ ID NOs: 56 and 209, respectively; SEQ ID NOs: 204 and 207, respectively; SEQ ID NOs: 56 and 210, respectively; SEQ ID NOs: 56 and 211, respectively; SEQ ID NOs: 204 and 210, respectively; SEQ ID NOs: 56 and 212, respectively; SEQ ID NOs: 56 and 213, respectively; and SEQ ID NOs: 204 and 212, respectively.

[0313] In some embodiments, the antibody, or antigen binding fragment thereof, comprises an HC and an LC wherein the HC comprises SEQ ID NO: 53 and the LC comprises SEQ ID NO: 58. In some embodiments, the antibody, or antigen binding fragment thereof, comprises a HC and a LC wherein the HC comprises SEQ ID NO: 53 and the LC comprises SEQ ID NO: 70. In some embodiments, the antibody, or antigen binding fragment thereof, comprises a HC and a LC wherein the HC comprises SEQ ID NO: 53 and the LC comprises SEQ ID NO: 67. In some embodiments, the antibody, or antigen binding fragment thereof, comprises a HC and a LC wherein the HC comprises SEQ ID NO: 53 and the LC comprises SEQ ID NO: 66. In some embodiments, the antibody, or antigen binding fragment thereof, comprises a HC and a LC wherein the HC comprises SEQ ID NO: 53 and the LC comprises SEQ ID NO: 63. In some embodiments, the antibody, or antigen binding fragment thereof, comprises a HC and a LC wherein the HC comprises SEQ ID NO: 54 and the LC comprises SEQ ID NO: 58. In some embodiments, the antibody, or antigen92FH13167949.1BPX-05925 binding fragment thereof, comprises a HC and a LC wherein the HC comprises SEQ ID NO: 54 and the LC comprises SEQ ID NO: 66. In some embodiments, the antibody, or antigen binding fragment thereof, comprises a HC and a LC wherein the HC comprises SEQ ID NO: 54 and the LC comprises SEQ ID NO: 59. In some embodiments, the antibody, or antigen binding fragment thereof, comprises a HC and a LC wherein the HC comprises SEQ ID NO: 54 and the LC comprises SEQ ID NO: 60. In some embodiments, the antibody, or antigen binding fragment thereof, comprises a HC and a LC wherein the HC comprises SEQ ID NO: 54 and the LC comprises SEQ ID NO: 61. In some embodiments, the antibody, or antigen binding fragment thereof, comprises a HC and a LC wherein the HC comprises SEQ ID NO: 54 and the LC comprises SEQ ID NO: 67. In some embodiments, the antibody, or antigen binding fragment thereof, comprises a HC and a LC wherein the HC comprises SEQ ID NO: 55 and the LC comprises SEQ ID NO: 58. In some embodiments, the antibody, or antigen binding fragment thereof, comprises a HC and a LC wherein the HC comprises SEQ ID NO: 55 and the LC comprises SEQ ID NO: 63. In some embodiments, the antibody, or antigen binding fragment thereof, comprises a HC and a LC wherein the HC comprises SEQ ID NO: 55 and the LC comprises SEQ ID NO: 65. In some embodiments, the antibody, or antigen binding fragment thereof, comprises a HC and a LC wherein the HC comprises SEQ ID NO: 55 and the LC comprises SEQ ID NO: 67. In some embodiments, the antibody, or antigen binding fragment thereof, comprises a HC and a LC wherein the HC comprises SEQ ID NO: 56 and the LC comprises SEQ ID NO: 67. In some embodiments, the antibody, or antigen binding fragment thereof, comprises a HC and a LC wherein the HC comprises SEQ ID NO: 56 and the LC comprises SEQ ID NO: 68. In some embodiments, the antibody, or antigen binding fragment thereof, comprises a HC and a LC wherein the HC comprises SEQ ID NO: 56 and the LC comprises SEQ ID NO: 69. In some embodiments, the antibody, or antigen binding fragment thereof, comprises a HC and a LC wherein the HC comprises SEQ ID NO: 56 and the LC comprises SEQ ID NO: 58. In some embodiments, the antibody, or antigen binding fragment thereof, comprises a HC and a LC wherein the HC comprises SEQ ID NO: 56 and the LC comprises SEQ ID NO: 66. In some embodiments, the antibody, or antigen binding fragment thereof, comprises a HC and a LC wherein the HC comprises SEQ ID NO: 56 and the LC comprises SEQ ID NO: 62. In some embodiments, the antibody, or antigen binding fragment thereof, comprises a HC and a LC wherein the HC comprises SEQ ID NO: 56 and the LC comprises SEQ ID NO: 63. In some embodiments, the antibody, or antigen binding fragment thereof, comprises a HC and a LC wherein93FH13167949.1BPX-05925 the HC comprises SEQ ID NO: 56 and the LC comprises SEQ ID NO: 64. In some embodiments, the antibody, or antigen binding fragment thereof, comprises a HC and a LC wherein the HC comprises SEQ ID NO: 56 and the LC comprises SEQ ID NO: 65. In some embodiments, the antibody, or antigen binding fragment thereof, comprises a HC and a LC wherein the HC comprises SEQ ID NO: 57 and the LC comprises SEQ ID NO: 58. In some embodiments, the antibody, or antigen binding fragment thereof, comprises a HC and a LC wherein the HC comprises SEQ ID NO: 56 and the LC comprises SEQ ID NO: 205. In some embodiments, the antibody, or antigen binding fragment thereof, comprises a HC and a LC wherein the HC comprises SEQ ID NO: 56 and the LC comprises SEQ ID NO: 206. In some embodiments, the antibody, or antigen binding fragment thereof, comprises a HC and a LC wherein the HC comprises SEQ ID NO: 56 and the LC comprises SEQ ID NO: 207. In some embodiments, the antibody, or antigen binding fragment thereof, comprises a HC and a LC wherein the HC comprises SEQ ID NO: 204 and the LC comprises SEQ ID NO: 66. In some embodiments, the antibody, or antigen binding fragment thereof, comprises a HC and a LC wherein the HC comprises SEQ ID NO: 204 and the LC comprises SEQ ID NO: 205. In some embodiments, the antibody, or antigen binding fragment thereof, comprises a HC and a LC wherein the HC comprises SEQ ID NO: 56 and the LC comprises SEQ ID NO: 208. In some embodiments, the antibody, or antigen binding fragment thereof, comprises a HC and a LC wherein the HC comprises SEQ ID NO: 56 and the LC comprises SEQ ID NO: 209. In some embodiments, the antibody, or antigen binding fragment thereof, comprises a HC and a LC wherein the HC comprises SEQ ID NO: 204 and the LC comprises SEQ ID NO: 207. In some embodiments, the antibody, or antigen binding fragment thereof, comprises a HC and a LC wherein the HC comprises SEQ ID NO: 56 and the LC comprises SEQ ID NO: 210. In some embodiments, the antibody, or antigen binding fragment thereof, comprises a HC and a LC wherein the HC comprises SEQ ID NO: 56 and the LC comprises SEQ ID NO: 211. In some embodiments, the antibody, or antigen binding fragment thereof, comprises a HC and a LC wherein the HC comprises SEQ ID NO: 204 and the LC comprises SEQ ID NO: 210. In some embodiments, the antibody, or antigen binding fragment thereof, comprises a HC and a LC wherein the HC comprises SEQ ID NO: 56 and the LC comprises SEQ ID NO: 212. In some embodiments, the antibody, or antigen binding fragment thereof, comprises a HC and a LC wherein the HC comprises SEQ ID NO: 56 and the LC comprises SEQ ID NO: 213. In some embodiments, the antibody, or antigen94FH13167949.1BPX-05925 binding fragment thereof, comprises a HC and a LC wherein the HC comprises SEQ ID NO: 204 and the LC comprises SEQ ID NO: 212.Exemplary anti-C2 antibodies

[0314] In some embodiments, an anti-C2 antibody or antigen binding fragment described herein comprises the VH CDR1-CDR3 and VL CDR1-CDR3 as set forth in Table 4. In some embodiments, an anti-C2 antibody or antigen binding fragment described herein comprises the VH and the VL as set forth in Table 4. In some embodiments, means for binding C2 are provided in Table 4.Table 4: Anti-C2 Antibody and Antigen Binding Fragment Sequences95FH13167949.1BPX-05925

[0315] In some embodiments, an antibody of Table 4 comprises a histidine at one or more amino acid positions including position L26, L67, L93, and H97 (numbering according to Kabat).Table 5: Anti-C2 Antibody and Antigen Binding Fragment Sequences

[0316] In some embodiments, an anti-C2 antibody or antigen binding fragment described herein comprises the VH CDR1-CDR3 and VL CDR1-CDR3 as set forth in Table 5. In some embodiments, an anti-C2 antibody or antigen binding fragment described herein comprises the VH and the VL as set forth in Table 5. In some embodiments, means for binding C2 are provided in Table 5.

[0317] In some embodiments, an antibody of Table 5 comprises a histidine at one or more amino acid positions including position L26, L67, L93, and H97 (numbering according to Kabat).Methods for producing the anti-C2 antibodies and antigen binding fragments thereof

[0318] The antibodies or antigen-binding fragments thereof described herein can be produced using a variety of techniques known in the art of molecular biology and protein chemistry. For example, a nucleic acid encoding one or both of the heavy and light chain polypeptides of an antibody can be inserted into an expression vector that contains transcriptional and translational regulatory sequences, which include, e.g., promoter sequences, ribosomal binding sites, transcriptional start and stop sequences, translational start and stop sequences, transcription96FH13167949.1BPX-05925 terminator signals, polyadenylation signals, and enhancer or activator sequences. The regulatory sequences include a promoter and transcriptional start and stop sequences. In addition, the expression vector can include more than one replication system such that it can be maintained in two different organisms, for example in mammalian or insect cells for expression and in a prokaryotic host for cloning and amplification.

[0319] Several possible vector systems are available for the expression of cloned heavy chain and light chain polypeptides from nucleic acids in mammalian cells. One class of vectors relies upon the integration of the desired gene sequences into the host cell genome. Cells which have stably integrated DNA can be selected by simultaneously introducing drug resistance genes such as E. coli gpt (Mulligan and Berg (1981) Proc Natl Acad Sci USA 78:2072) or Tn5 neo (Southern and Berg (1982) MolAppl Genetl:327). The selectable marker gene can be either linked to the DNA gene sequences to be expressed, or introduced into the same cell by co-transfection (Wigler et al. (1979) Cell 16:77). A second class of vectors utilizes DNA elements which confer autonomously replicating capabilities to an extrachromosomal plasmid. These vectors can be derived from animal viruses, such as bovine papillomavirus (Sarver et al. (1982) Proc Natl Acad Sci USA, 79:7147), cytomegalovirus, polyoma virus (Deans et al. (1984) Proc Natl Acad Sci USA 81 : 1292), or SV40 virus (Lusky and Botchan (1981) Nature 293:79).

[0320] The expression vectors can be introduced into cells in a manner suitable for subsequent expression of the nucleic acid. The method of introduction is largely dictated by the targeted cell type, discussed below. Exemplary methods include CaPCE precipitation, liposome fusion, cationic liposomes, electroporation, viral infection, dextran-mediated transfection, polybrene-mediated transfection, protoplast fusion, and direct micro injection. Appropriate host cells for the expression of antibodies or antigen-binding fragments thereof include yeast, bacteria, insect, plant, and mammalian cells. Of particular interest are bacteria such as E. coli, fungi such as Saccharomyces cerevisiae and Pichia pastoris, insect cells such as SF9, mammalian cell lines (e.g., human cell lines), as well as primary cell lines.

[0321] Following expression, the antibodies and fragments thereof can be isolated. An antibody or fragment thereof can be isolated or purified in a variety of ways known to those skilled in the art depending on what other components are present in the sample. Standard purification methods include electrophoretic, molecular, immunological, and chromatographic techniques, including ion exchange, hydrophobic, affinity, and reverse-phase HPLC chromatography. For97FH13167949.1BPX-05925 example, an antibody can be purified using a standard anti-antibody column (e.g., a protein-A or protein-G column). Ultrafiltration and diafiltration techniques, in conjunction with protein concentration, are also useful. See, e.g., Scopes (1994) "Protein Purification, 3rd edition," Springer- Verlag, New York City, New York. The degree of purification necessary will vary depending on the desired use. In some instances, no purification of the expressed antibody or fragments thereof will be necessary. Methods for determining the yield or purity of a purified antibody or fragment thereof are known in the art and include, e.g, Bradford assay, UV spectroscopy, Biuret protein assay, Lowry protein assay, amido black protein assay, high pressure liquid chromatography (HPLC), mass spectrometry (MS), and gel electrophoretic methods (e.g., using a protein stain such as Coomassie Blue or colloidal silver stain).Anti-C2 Conjugates

[0322] In some aspects, the disclosure provides an anti-C2 conjugate comprising means for binding C2 and at least one regulator of complement activation (RCA) polypeptide. In some embodiments, means for binding C2 are provided in Table 4. In some embodiments, means for binding C2 are provided in Table 5. In some aspects, the disclosure provides an anti-C2 conjugate comprising an antibody, or antigen binding fragment thereof, that specifically binds C2, and at least one regulator of complement activation (RCA) polypeptide. In some embodiments, the antibody or antigen binding fragment thereof is an anti-C2 antibody or antigen binding fragment described herein.

[0323] In some embodiments, the anti-C2 conjugate an antibody, or antigen binding fragment thereof comprising a fragment crystallizable region (Fc region). In some embodiments, the anti-C2 antibody or antigen binding fragment comprises an Fc region associated to one antigen binding fragment (Fab) region (i.e., one Fab arm). In some embodiments, the anti-C2 antibody or antigen binding fragment comprises an Fc region associated to two Fab regions (i.e., two Fab arms).

[0324] In some embodiments, the anti-C2 conjugate comprises 1 to 5 RCA polypeptides. In some embodiments, the antibody or antigen binding fragment or the means for binding C2 is conjugated to the at least one RCA polypeptide via a linker. In some embodiments, the anti-C2 conjugate comprises two or more RCA polypeptides. In some embodiments, the anti-C2 conjugate comprises 2 RCA polypeptides. In some embodiments, the two or two or more RCA polypeptides98FH13167949.1BPX-05925 are the same. In some embodiments, the two or two or more RCA polypeptides are different. In some embodiments, the two or more RCA polypeptides are linked to each other via a linker.

[0325] In some embodiments, where the two or more RCA polypeptides are linked to each other via a linker, the linker is a peptide linker. In some embodiments, the peptide linker is a GlySer linker. In some embodiments, the GlySer linker is a (GxSy)zlinker, wherein x is 3-6, y is 0 or 1, and z is 1-5. In some embodiments, the GlySer linker is a (GGGGS) (SEQ ID NO: 108), (GGGGS)(GGGGS) (SEQ ID NO: 115) or (GGGGS)(GGGGS)(GGGGS) (SEQ ID NO: 122) linker. In some embodiments, the GlySer linker is a (GGGGS)n(PGGGS)xlinker, wherein P is proline, a (GGGPS)n(GGGGS)xlinker, wherein P is proline, a (GGGGA)n(GGGGS)xlinker, where A is alanine, or a (GGGGQ)n(GGGGS)xlinker, wherein Q is glutamine, where for each linker n is 1-3, and x is 0 or 1, optionally wherein n is 1 or 2.

[0326] In some embodiments, the anti-C2 conjugate comprises (i) an anti-C2 antibody or antigen binding fragment thereof comprising three HC CDRs and three LC CDRs, and (ii) one or more RCA polypeptides (e.g., 1-5). In some embodiments, the anti-C2 conjugate comprises (i) an anti-C2 antibody or antigen binding fragment thereof comprising a CDRH1, a CDRH2, a CDRH3, a variable heavy chain sequence, a constant heavy chain sequence, a CDRL1, a CDRL2, a CDRL3, a variable light chain sequence, a constant light chain sequence, and (ii) one or more (e.g., 1-5) RCA polypeptides. In some embodiments, the anti-C2 conjugate comprises an anti-C2 antibody or antigen binding fragment thereof comprising a CDRH1, a CDRH2, a CDRH3, a CDRL1, a CDRL2, and a CDRL3 as provided in Table 11.

[0327] In some embodiments, the anti-C2 conjugate comprises an anti-C2 antibody comprising a VH provided in Table 4, Table 5, or Table 11. In some embodiments, the anti-C2 conjugate comprises an anti-C2 antibody comprising a VL as provided in Table 4, Table 5, or Table 11. In some embodiments, the anti-C2 conjugate comprises an anti-C2 antibody comprising a VH and a VL as provided in Table 4, Table 5, or Table 11.

[0328] In some embodiments, the anti-C2 conjugate comprises an anti-C2 antibody comprising a HC (i.e., variable and constant regions) as provided in Table 11. In some embodiments, the anti-C2 conjugate comprises an anti-C2 antibody comprising a LC (i.e., variable and constant regions) as provided in Table 11. In some embodiments, the anti-C2 conjugate comprises an anti-C2 antibody comprising a HC and a LC as provided in Table 11.99FH13167949.1BPX-05925

[0329] In some embodiments, the anti-C2 conjugate comprises a formula of: ANTIBODY- (LINKERlxi-RCAl)n-LINKER2X2-RCA2, where "n" is 0-5, XI is independently 0 or 1 and X2 is 0 or 1. In some embodiments “ANTIBODY” is an anti-C2 antibody or antigen binding fragment thereof. In some embodiments, “ANTIBODY” is an anti-C2 antibody or antigen binding fragment thereof described herein. In some embodiments, “RCA1” and “RCA2” are each independently a polypeptide of the RCA family. In some embodiments, “LINKER1” and “LINKER” are each independently a linker (e.g., a peptide linker). In some embodiments, RCA1 and RCA2 are each independently selected from SEQ ID NOs: 89-104.

[0330] In some embodiments, RCA1 and RCA2 are each independently selected from SEQ ID NOs: 89, 93, or 97, and “n” is 1 and XI and X2 are each 1 or wherein RCA2 is SEQ ID NOs: 89, 93, or 97, and “n” is 0 and X2 is 1.

[0331] In some embodiments, the anti-C2 conjugate comprises a formula of: ANTIBODY- (LINKER1-RCA1)-RCA2. In some embodiments, the anti-C2 conjugate comprises a formula of: ANTIBODY-(LINKER1-RCA1)-(LINKER1-RCA1)-RCA2. In some embodiments, the anti-C2 conjugate comprises a formula of: ANTIBOD Y-(LINKER1-RCA1 )-(LINKERl-RCAl )- (LINKER1-RCA1)-RCA2. In some embodiments, the anti-C2 conjugate comprises a formula of: ANTIBOD Y-(LINKER1 -RCA1 )-(LINKERl -RCA1 )-(LINKERl -RCA1 )-(LINKERl -RCA1 )- RCA2. In some embodiments, the anti-C2 conjugate comprises a formula of: ANTIBODY- (LINKER1 -RCA1 )-(LINKERl -RCA1 )-(LINKERl -RCA1 )-(LINKERl -RCA1 )-(LINKERl - RCA1)-RCA2. In some embodiments, the anti-C2 conjugate comprises a formula of: ANTIBODY- RCA2.

[0332] In some embodiments, the anti-C2 conjugate comprises a formula of: ANTIBODY- (LINKER1-RCA1)-LINKER2-RCA2. In some embodiments, the anti-C2 conjugate comprises a formula of: ANTIBODY-(LINKER1-RCA1)-(LINKER1-RCA1)-LINKER2-RCA2. In some embodiments, the anti-C2 conjugate comprises a formula of: ANTIBODY-(LINKERl-RCAl)- (LINKER1-RCA1)-(LINKER1-RCA1)-LINKER2-RCA2. In some embodiments, the anti-C2 conjugate comprises a formula of: ANTIBOD Y-(LINKER1-RCA1 )-(LINKERl-RCAl )- (LINKER1-RCA1)-(LINKER1-RCA1)-LINKER2-RCA2. In some embodiments, the anti-C2 conjugate comprises a formula of: ANTIBOD Y-(LINKER1-RCA1)-(LINKER1-RCA1)- (LINKER1 -RCA1 )-(LINKERl -RCA1 )-(LINKERl -RCA1 )-LINKER2-RCA2.100FH13167949.1BPX-05925

[0333] In some embodiments, the anti-C2 conjugate comprises a formula of: ANTIBODY- (RCA1)-LINKER2-RCA2. In some embodiments, the anti-C2 conjugate comprises a formula of: ANTIBODY-(RCA1)-(RCA1)-LINKER2-RCA2. In some embodiments, the anti-C2 conjugate comprises a formula of: ANTIBODY-(RCA1)-(RCA1)-(RCA1)-LINKER2-RCA2. In some embodiments, the anti-C2 conjugate comprises a formula of: ANTIBODY-(RCA1)-(RCA1)- (RCA1)-(RCA1)-LINKER2-RCA2. In some embodiments, the anti-C2 conjugate comprises a formula of: ANHBODY-(RCA1)-(RCA1)-(RCA1)-(RCA1)-(RCA1)-LINKER2-RCA2.

[0334] In some embodiments, the anti-C2 conjugate comprises an anti-C2 antibody comprising an HC conjugated to an RCA polypeptide by a linker, and an LC. In some embodiments, the anti-C2 conjugate comprises an anti-C2 antibody comprising an LC conjugated to an RCA polypeptide by a linker, and an HC. In some embodiments, the anti-C2 conjugate comprises an anti-C2 antibody comprising i) an HC, a linker, and an RCA polypeptide, and ii) an LC. In some embodiments, the anti-C2 conjugate comprises an anti-C2 antibody comprising i) from the N-terminus to the C-terminus, an HC, a linker, and an RCA polypeptide, and ii) an LC. In some embodiments, the anti-C2 conjugate comprises an anti-C2 antibody comprising i) an HC, a first linker, a first RCA, a second linker, and a second RCA, and ii) an LC. In some embodiments, the anti-C2 conjugate comprises an anti-C2 antibody comprising i) from the N-terminus to the C- terminus, an HC, a first linker, a first RCA, a second linker, and a second RCA, and ii) an LC. In some embodiments, the anti-C2 conjugate comprises an anti-C2 antibody comprising i) an HC, a first linker, a first RCA, a second linker, a second RCA, a third linker, and a third RCA, and ii) an LC. In some embodiments, the anti-C2 conjugate comprises an anti-C2 antibody comprising i) from the N-terminus to the C-terminus, an HC, a first linker, a first RCA, a second linker, a second RCA, a third linker, and a third RCA, and ii) an LC. In some embodiments, the anti-C2 conjugate comprises an anti-C2 antibody comprising i) an HC, a first linker, a first RCA, a second linker, a second RCA, a third linker, a third RCA, a fourth linker, and a fourth RCA, and ii) an LC. In some embodiments, the anti-C2 conjugate comprises an anti-C2 antibody comprising i) from the N- terminus to the C-terminus, an HC, a first linker, a first RCA, a second linker, a second RCA, a third linker, a third RCA, a fourth linker, and a fourth RCA, and ii) an LC. In some embodiments, the anti-C2 conjugate comprises an anti-C2 antibody comprising i) an HC, a first linker, a first RCA, a second linker, a second RCA, a third linker, a third RCA, a fourth linker, a fourth RCA, a fifth linker, and a fifth RCA, and ii) an LC. In some embodiments, the anti-C2 conjugate comprises101FH13167949.1BPX-05925 an anti-C2 antibody comprising i) from the N-terminus to the C-terminus, an HC, a first linker, a first RCA, a second linker, a second RCA, a third linker, a third RCA, a fourth linker, a fourth RCA, a fifth linker, and a fifth RCA, and ii) an LC.

[0335] In some embodiments, the anti-C2 conjugate comprises an anti-C2 antibody comprising i) an HC and ii) an LC, a linker, and an RCA. In some embodiments, the anti-C2 conjugate comprises an anti-C2 antibody comprising i) an HC, and ii) from the N-terminus to the C- terminus, an LC, a linker, and an RCA. In some embodiments, the anti-C2 conjugate comprises an anti-C2 antibody comprising i) an LC, a first linker, a first RCA, a second linker, and a second RCA, and ii) an HC. In some embodiments, the anti-C2 conjugate comprises an anti-C2 antibody comprising i) from the N-terminus to the C-terminus, an LC, a first linker, a first RCA, a second linker, and a second RCA, and ii) an HC. In some embodiments, the anti-C2 conjugate comprises an anti-C2 antibody comprising i) an LC, a first linker, a first RCA, a second linker, a second RCA, a third linker, and a third RCA, and ii) an HC. In some embodiments, the anti-C2 conjugate comprises an anti-C2 antibody comprising i) from the N-terminus to the C-terminus, an LC, a first linker, a first RCA, a second linker, a second RCA, a third linker, and a third RCA, and ii) an HC. In some embodiments, the anti-C2 conjugate comprises an anti-C2 antibody comprising i) an LC, a first linker, a first RCA, a second linker, a second RCA, a third linker, a third RCA, a fourth linker, and a fourth RCA, and ii) an HC. In some embodiments, the anti-C2 conjugate comprises an anti- C2 antibody comprising i) from the N-terminus to the C-terminus, an LC, a first linker, a first RCA, a second linker, a second RCA, a third linker, a third RCA, a fourth linker, and a fourth RCA, and ii) an HC. In some embodiments, the anti-C2 conjugate comprises an anti-C2 antibody comprising i) an LC, a first linker, a first RCA, a second linker, a second RCA, a third linker, a third RCA, a fourth linker, a fourth RCA, a fifth linker, and a fifth RCA, and ii) an HC. In some embodiments, the anti-C2 conjugate comprises an anti-C2 antibody comprising i) from the N-terminus to the C- terminus, an LC, a first linker, a first RCA, a second linker, a second RCA, a third linker, a third RCA, a fourth linker, a fourth RCA, a fifth linker, and a fifth RCA, and ii) an HC.RCA polypeptide

[0336] To prevent unchecked activation of the complement cascade and damage to host cells or tissues, specific proteins have evolved as regulators of complement. Both transmembrane and soluble forms of these regulators exist, acting at all levels of the complement cascade. These102FH13167949.1BPX-05925 proteins are members of a group of genetically, structurally, and functionally related proteins called the regulators of complement activation (RCA). As its name implies, the function of this proteins is to provide homeostasis by tightly controlling the complement system.

[0337] RCA polypeptides, in particular Factor H (FH), C4b binding protein (C4BP), membrane cofactor protein (MCP), complement receptor 1 (CR1) and decay accelerating factor (DAF), regulate complement activities through several mechanisms. RCA proteins may act as a cofactor co-factor activity) for Factor I (FI) to degrade C4b-containing complexes or C3b- containing complexes, including the C3 convertases (C4bC2a, C3bBb) and C5 convertase (C4bC2aC3b, C3bBbC3b) of the classical / lectin pathway and the alternative pathway of complement activation. In addition, RCA polypeptides may act by accelerating decay of the C3 and / or C5 convertases by binding to specific convertase proteins. The regions of the RCA polypeptide responsible for these actions are referred to as complement-control-protein (CCP) domains and consists of about 60-70 amino acid residues.

[0338] The conjugates described herein comprise at least one RCA polypeptide. In some embodiments, the at least one RCA polypeptide is conjugated to the heavy chain of the antibody. In some embodiments, the at least one RCA polypeptide is conjugated to the light chain of the antibody. In some embodiments, the at least one RCA polypeptide is conjugated to the N-terminus of the heavy chain. In some embodiments, the at least one RCA polypeptide is conjugated to the C- terminus of the heavy chain. In some embodiments, the at least one RCA polypeptide is conjugated to the N-terminus of the light chain. In some embodiments, the at least one RCA polypeptide is conjugated to the C-terminus of the light chain. In some embodiments, an anti-C2 conjugates comprises an RCA polypeptide conjugated to the heavy chain and an RCA polypeptide conjugated to the light chain, wherein the RCA polypeptides are the same or different.

[0339] In some embodiments, the at least one RCA polypeptide is selected from FH1-4, FH1-5, FH19-20, DAF1-4, DAF2-4, MCP1-4, MCP2-4, MCP3-4, C4BP1-3, C4BP1-4, CR1.1-3, CR1.8-10, CR1.15-17, and any combination thereof.

[0340] In some embodiments, the RCA polypeptide comprises an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to an amino acid sequence selected from SEQ ID NOs: 89-104. In some embodiments, the RCA polypeptide comprises an amino acid sequence selected from SEQ ID NOs: 89-104.103FH13167949.1BPX-05925

[0341] In some embodiments, the anti-C2 conjugate comprises a factor H (FH) polypeptide, or portion thereof. FH is a large (155 kilodaltons), soluble glycoprotein that circulates in human plasma at typical concentrations of 200-300 micrograms per milliliter. Its principal function is to regulate the alternative pathway and the amplification loop of the complement system. Factor H is composed of 20 individual CCP domains. The complement regulatory activities of FH are mediated by the N-terminal CCP1-4 domains, which harbor a C3b-binding site. Factor H acts by preventing the assembly of the C3bBb alternative pathway C3 convertase enzyme through binding to C3b, facilitating the decay of the C3 convertase if already formed by displacing bound Bb from C3b, or cleaving bound C3b in conjunction with FI into the inactive form iC3b. Interaction of FH with C3b also allows for regulation of the C5 convertases.

[0342] In some embodiments, the anti-C2 conjugate comprises an FH1-4 polypeptide. In some embodiments, the anti-C2 conjugate comprises an FH1-4 polypeptide comprising an amino acid sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 89. In some embodiments, the anti-C2 conjugate comprises an FH1-4 polypeptide comprising the amino acid sequence of SEQ ID NO: 89.

[0343] In some embodiments, the anti-C2 conjugate comprises an FH1-5 polypeptide. In some embodiments, the anti-C2 conjugate comprises an FH1-5 polypeptide comprising an amino acid sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 90. In some embodiments, the anti-C2 conjugate comprises an FH1-5 polypeptide comprising the amino acid sequence of SEQ ID NO: 90.

[0344] In some embodiments, the anti-C2 conjugate comprises an FH19-20 polypeptide comprising an amino acid sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the ammo acid sequence of SEQ ID NO: 91. In some embodiments, the anti-C2 conjugate comprises an FH19-20 polypeptide comprising the amino acid sequence of SEQ ID NO: 91.

[0345] In some embodiments, the anti-C2 conjugate comprises a DAF polypeptide. DAF (CD55) is a 70,000 MW membrane protein that protects cells from activation of autologous complement on their surfaces. The functional sites of DAF are contained within CCPs 1 -4. DAF104FH13167949.1BPX-05925 acts to accelerate the decay of the classical / lecithin and alternative C3 and C5 convertases. DAF is capable of regulating the classical, lectin, and alternative complement pathways.

[0346] In some embodiments, the anti-C2 conjugate comprises an DAF1-4 polypeptide comprising an amino acid sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the ammo acid sequence of SEQ ID NO: 92. In some embodiments, the anti-C2 conjugate comprises an DAF1-4 polypeptide comprising the amino acid sequence of SEQ ID NO: 92.

[0347] In some embodiments, the anti-C2 conjugate comprises a DAF2-4 polypeptide. In some embodiments, the anti-C2 conjugate comprises a DAF2-4 polypeptide comprising an amino acid sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 93. In some embodiments, the anti-C2 conjugate comprises a DAF2-4 polypeptide comprising the amino acid sequence of SEQ ID NO: 93.

[0348] In some embodiments, the anti-C2 conjugate comprises a MCP polypeptide. MCP (CD46) is a type-I membrane glycoprotein that binds C3b and C4b deposited on host cells. The functional sites of MCP are contained within CCPs 1-4. MCP then serves as a cofactor for their proteolytic cleavage by FI, a process that irreversibly prevents convertase formation. Genetic loss of MCP has been associated with the development of atypical hemolytic-uremic syndrome (aHUS).

[0349] In some embodiments, the anti-C2 conjugate comprises an MCP 1-4 polypeptide comprising an amino acid sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the ammo acid sequence of SEQ ID NO: 94. In some embodiments, the anti-C2 conjugate comprises an MCP1-4 polypeptide comprising the amino acid sequence of SEQ ID NO: 94.

[0350] In some embodiments, the anti-C2 conjugate comprises an MCP2-4 polypeptide. In some embodiments, the anti-C2 conjugate comprises an MCP2-4 polypeptide comprising an amino acid sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 95. In some embodiments, the anti-C2 conjugate comprises an MCP2-4 polypeptide comprising the amino acid sequence of SEQ ID NO: 95.

[0351] In some embodiments, the anti-C2 conjugate comprises an MCP3-4 polypeptide. In some embodiments, the anti-C2 conjugate comprises an MCP3-4 polypeptide comprising an amino105FH13167949.1BPX-05925 acid sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 96. In some embodiments, the anti-C2 conjugate comprises an MCP3-4 polypeptide comprising the amino acid sequence of SEQ ID NO: 96.

[0352] In some embodiments, the anti-C2 conjugate comprises a C4BP polypeptide. C4BP, a 570 kDa glycoprotein, is a major fluid phase inhibitor of the classical and lectin pathways of the complement system. It consists of seven identical 70 kDa a-chains and a 45 kDa P-chain that are linked at their carboxy-terminal ends by short amphipathic helices further stabilized by disulfide bonds. The a- chains and P-chain contain eight and three CCP domains. Complement inhibition is achieved by binding to and restricting the role of activated complement component C4b. C4BP has been shown to inhibit the formation of C3 and C5 convertases, accelerate the decay of the convertases, and act as a co-factor for Factor I which cleaves and thereby inactivates fluid phase and cell-bound C4b. The co-factor activity of the protein has been linked to regions within CCP1-4.

[0353] In some embodiments, the anti-C2 conjugate comprises an C4BP1-3 polypeptide comprising an amino acid sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the ammo acid sequence of SEQ ID NO: 97. In some embodiments, the anti-C2 conjugate comprises an C4BP1-3 polypeptide comprising the amino acid sequence of SEQ ID NO: 97.

[0354] In some embodiments, the anti-C2 conjugate comprises a C4BP1-4 polypeptide. In some embodiments, the anti-C2 conjugate comprises a C4BP1-4 polypeptide comprising an amino acid sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 98. In some embodiments, the anti-C2 conjugate comprises a C4BP1-4 polypeptide comprising the amino acid sequence of SEQ ID NO: 98.

[0355] In some embodiments, the anti-C2 conjugate comprises a CR1 polypeptide. CR1 (CD35) is a membrane-bound protein having an extracellular domain of 1930 residues, a 25-residue transmembrane domain and a 43 amino acid C terminal cytoplasmic region. The extracellular domain of the most common form of CR1 is composed of a series of 30 CCPs. The sequence homology between CCPs ranges between 60 and 99 percent. The CCPs are distributed in four long homologous repeats (LHRs A, B, C, and D). CR1 also exists, at low levels, in a soluble form (sCRl) resulting from proteolytic cleavage in terminal secretory vesicles or in the cell membrane.106FH13167949.1BPX-05925CR1 competitively displaces the Factor Bb and C2a catalytic fragments from the C3 convertases (C4bC2a, C3bBb) and C5 convertases (C4bC2aC3b, C3bBbC3b) formed during complement activation. CR1 also acts as a co-factor for FI, a serum protease that can cleave CR1 -bound C3b and C4b into the inactive forms iC3b and iC4b / C4c, to further inhibit complement activation. CCPs 1-3 are required for C4b binding and decay-accelerating activity, while CCPs 8-10 and 15-17 are required for C3b and C4b binding and cofactor activity. Therefore, CR1 is capable of regulating the classical, lectin, and alternative complement pathways.

[0356] In some embodiments, the anti-C2 conjugate comprises an CR1.1-3 polypeptide comprising an amino acid sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the ammo acid sequence of SEQ ID NO: 99. In some embodiments, the anti-C2 conjugate comprises an CR1.1-3 polypeptide comprising the amino acid sequence of SEQ ID NO: 99.

[0357] In some embodiments, the anti-C2 conjugate comprises a CR1.8-10 polypeptide. In some embodiments, the anti-C2 conjugate comprises an CR1.8-10 polypeptide comprising an amino acid sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 100. In some embodiments, the anti-C2 conjugate comprises an CR1.8-10 polypeptide comprising the amino acid sequence of SEQ ID NO: 100.

[0358] In some embodiments, the anti-C2 conjugate comprises a CR1.8-10.N19S.N88S (CR1.8-10.N509S.N578S) polypeptide. In some embodiments, the anti-C2 conjugate comprises a CR1.8-10.N19S.N88S (CR1.8-10.N509S.N578S) polypeptide comprising an amino acid sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 101. In some embodiments, the anti-C2 conjugate comprises a CR1.8-10.N19S.N88S (CR1.8-10.N509S.N578S) polypeptide comprising the amino acid sequence of SEQ ID NO: 101.

[0359] In some embodiments, the anti-C2 conjugate comprises a CR1.8-11 polypeptide. In some embodiments, the anti-C2 conjugate comprises a CR1.8-11 polypeptide comprising an amino acid sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 102. In some embodiments, the anti-C2 conjugate comprises a CR1.8-11 polypeptide comprising the amino acid sequence of SEQ ID NO: 102.107FH13167949.1BPX-05925

[0360] In some embodiments, the anti-C2 conjugate comprises a CR1.8-11 N19S.N88S.N212S polypeptide. In some embodiments, the anti-C2 conjugate comprises a CR1.8- 11 N19S.N88S.N212S polypeptide comprising an amino acid sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 103. In some embodiments, the anti-C2 conjugate comprises a CR1.8-11 N19S.N88S.N212S polypeptide comprising the amino acid sequence of SEQ ID NO: 103.

[0361] In some embodiments, the anti-C2 conjugate comprises a CR1.15-17 polypeptide. In some embodiments, the anti-C2 conjugate comprises an CR1.15-17 polypeptide comprising an amino acid sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 104. In some embodiments, the anti-C2 conjugate comprises an CR1.15-17 polypeptide comprising the amino acid sequence of SEQ ID NO: 104.

[0362] In some embodiments, the two or more RCA polypeptides independently comprise SEQ ID NOs: 89 and 93. In some embodiments, the single RCA peptide comprises SEQ ID NO: 93. In some embodiments, the single RCA peptide comprises SEQ ID NO: 98.

[0363] In some embodiments, the anti-C2 conjugate comprises 1 to 5 (e.g., 1, 2, 3, 4, or 5) RCA polypeptide(s). In some embodiments, the anti-C2 conjugate comprises any combination of the RCA polypeptides provided in SEQ ID NOs: 89-104. In some embodiments, when the anti-C2 is conjugated to multiple RCA polypeptides the RCA polypeptides are linked directly to each other (e.g., without the use of an intermediate linker). In some embodiments, when the anti-C2 conjugate is conjugated to multiple RCA polypeptides the RCA polypeptides are conjugated to each other via a linker (e.g., a linker as provided in SEQ ID NOs: 105-168). In some embodiments, the at least one RCA polypeptide is conjugated directly to the HC or the LC of the anti-C2 antibody, or antigen binding fragment thereof, (e.g., without the use of an intermediate linker). In some embodiments, the at least one RCA polypeptide is conjugated to the HC of the anti-C2 antibody, or antigen binding fragment thereof, via a linker (e.g., a linker as provided in SEQ ID NOs: 105-168). In some embodiments, the at least one RCA polypeptide is conjugated to the LC of the anti-C2 antibody, or antigen binding fragment thereof, via a linker (e.g., a linker as provided in SEQ ID NOs: 105-168).Linker108FH13167949.1BPX-05925

[0364] In some embodiments, the anti-C2 conjugates comprise one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10) linkers to conjugate an HC to an RCA polypeptide, an LC to an RCA polypeptide, and / or multiple RCA polypeptides to each other. In some embodiments, the linker is a peptide linker. In some embodiments, the linker is a GlySer linker. In some embodiments, the GlySer linker is a (GxSy)zlinker, wherein x is 3-6, y is 0 or 1, and z is 1-5. In some embodiments, the GlySer linker is (GGGGS) (SEQ ID NO: 108), (GGGGS)(GGGGS) (SEQ ID NO: 115) or (GGGGS)(GGGGS)(GGGGS) (SEQ ID NO: 122). In some embodiments, the linker is a (GGGGS)n(PGGGS)xlinker, wherein P is proline, n is 1-3, and x is 0 or 1, optionally wherein n is 1 or 2. In some embodiments, the linker is a (GGGGA)n(GGGGS)xlinker, wherein A is alanine, n is 1-3, and x is 0 or 1, optionally wherein n is 1 or 2. In some embodiments, the r linker is a (GGGGQ)n(GGGGS)xlinker, wherein Q is glutamine, n is 1-3, and x is 0 or 1, optionally wherein n is 1 or 2. In some embodiments, the r linker is a (GGGPS)n(GGGGS)xlinker, wherein P is proline, n is 1-3, and x is 0 or 1, optionally wherein n is 1 or 2. In some embodiments, the linker is set forth in SEQ ID NOs: 105-168.Exemplary anti-C2 conjugates

[0365] In some embodiments, the at least one RCA polypeptide is conjugated to the heavy chain of the antibody. In some embodiments, the at least one RCA polypeptide is conjugated to the light chain of the antibody.

[0366] In some embodiments, the RCA polypeptide may be selected from: 1) a single RCA polypeptide of SEQ ID NOS: 89-104; 2) a single RCA polypeptide of SEQ ID NOS: 89-104 conjugated to the heavy chain or light chain directly; or 3) a single RCA polypeptide of SEQ ID NOS: 89-104 conjugated to the heavy chain or light chain via a linker sequence, such as a linker sequence of SEQ ID NOS: 105-168. In some embodiments, the RCA may be selected from: 1) a first and a second RCA polypeptide of SEQ ID NOS: 89-104, wherein the first and second RCA polypeptide may be the same or different; 2) a first and a second RCA polypeptide of SEQ ID NOS: 89-104, wherein the first and second RCA polypeptide may be the same or different, the first RCA polypeptide is directly conjugated to the heavy chain or light chain, and the second RCA polypeptide conjugated to the first RCA polypeptide directly; 3) a first and a second RCA polypeptide of SEQ ID NOS: 89-104, wherein the first and second RCA polypeptide may be the same or different, the first RCA polypeptide is directly conjugated to the heavy chain or light chain,109FH13167949.1BPX-05925 and the second RCA polypeptide conjugated to the first RCA polypeptide via a linker sequence, such as a linker sequence of SEQ ID NOS: 105-168; 4) a first and a second RCA polypeptide of SEQ ID NOS: 89-104, wherein the first and second RCA polypeptide may be the same or different, the first RCA polypeptide is conjugated to the heavy chain or light chain via a linker sequence, such as a linker sequence of SEQ ID NOS: 105-168, and the second RCA polypeptide conjugated to the first RCA polypeptide directly; or 5) a first and a second RCA polypeptide of SEQ ID NOS: 89- 104, wherein the first and second RCA polypeptide may be the same or different, the first RCA polypeptide is conjugated to the heavy chain or light chain via a linker sequence, such as a linker sequence of SEQ ID NOS: 105-168, and the second RCA polypeptide conjugated to the first RCA polypeptide via a linker sequence, such as a linker sequence of SEQ ID NOS: 105-168.

[0367] In some embodiments, the anti-C2 conjugate comprises an anti-C2 antibody comprising a heavy chain comprising an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequences selected from SEQ ID NOs: 53-57.

[0368] In some embodiments, the anti-C2 conjugate comprises an anti-C2 antibody comprising the amino acid sequence of SEQ ID NOs: 53-57.

[0369] In some embodiments, the anti-C2 conjugate comprises an anti-C2 antibody comprising a light chain comprising an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequences selected from SEQ ID NOs: 58-70.

[0370] In some embodiments, the anti-C2 conjugate comprises an anti-C2 antibody comprising the amino acid sequence of SEQ ID NOs: 58-70.

[0371] In some embodiments, the anti-C2 conjugate comprises a heavy chain and a light chain comprising amino acid sequences having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequences selected from SEQ ID NOs: 71 and 58, respectively, SEQ ID Nos: 74 and 58, respectively, SEQ ID NOs: 75 and 58, respectively, SEQ ID NOs: 72 and 58, respectively, SEQ ID NOs: 72 and 66, respectively, SEQ ID NOs: 73 and 62, respectively, SEQ ID NOs: 73 and 64, respectively, SEQ ID NOs: 76 and 58, respectively, SEQ ID NOs: 77 and 58, respectively, SEQ ID NOs: 78 and 58, respectively, SEQ ID NOs: 76 and 63, respectively, SEQ ID NOs: 77 and 63, respectively, SEQ ID NOs: 78 and 63, respectively, SEQ ID NOs: 79 and 63, respectively, SEQ ID NOs: 80 and 63, respectively, SEQ ID NOs: 81 and 63,110FH13167949.1BPX-05925 respectively, SEQ ID NOs: 79 and 65, respectively, SEQ ID NOs: 80 and 65, respectively, SEQ ID NOs: 81 and 65, respectively, SEQ ID NOs: 82 and 63, respectively, SEQ ID NOs: 83 and 63, respectively, SEQ ID NOs: 84 and 63, SEQ ID NOs: 73 and 63, SEQ ID NOs: 73 and 65, SEQ ID NOs: 73, and 66, SEQ ID NOs: 83 and 66, SEQ ID NOs: 88 and 65, SEQ ID NOs: 86 and 65, SEQ ID NOs: 85 and 58, SEQ ID NOs: 86 and 63, SEQ ID NOs: 86 and 66, SEQ ID NOs: 87 and 58, SEQ ID NOs: 88 and 63, and SEQ ID NOs: 88 and 68, respectively.

[0372] In some embodiments, the anti-C2 conjugate comprises a heavy chain and a light chain comprising the amino acid sequences selected from SEQ ID NOs: 71 and 58, respectively, SEQ ID NOs: 74 and 58, respectively, SEQ ID NOs: 75 and 58, respectively, SEQ ID NOs: 72 and 58, respectively, SEQ ID NOs: 72 and 66, respectively, SEQ ID NOs: 73 and 62, respectively, SEQ ID NOs: 73 and 64, respectively, SEQ ID NOs: 76 and 58, respectively, SEQ ID NOs: 77 and 58, respectively, SEQ ID NOs: 78 and 58, respectively, SEQ ID NOs: 76 and 63, respectively, SEQ ID NOs: 77 and 63, respectively, SEQ ID NOs: 78 and 63, respectively, SEQ ID NOs: 79 and 63, respectively, SEQ ID NOs: 80 and 63, respectively, SEQ ID NOs: 81 and 63, respectively, SEQ ID NOs: 79 and 65, respectively, SEQ ID NOs: 80 and 65, respectively, SEQ ID NOs: 81 and 65, respectively, SEQ ID NOs: 82 and 63, respectively, SEQ ID NOs: 83 and 63, respectively, SEQ ID NOs: 84 and 63, SEQ ID NOs: 73 and 63, SEQ ID NOs: 73 and 65, SEQ ID NOs: 73, and 66, SEQ ID NOs: 83 and 66, SEQ ID NOs: 88 and 65, SEQ ID NOs: 86 and 65, SEQ ID NOs: 85 and 58, SEQ ID NOs: 86 and 63, SEQ ID NOs: 86 and 66, SEQ ID NOs: 87 and 58, SEQ ID NOs: 88 and 63, and SEQ ID NOs: 88 and 66, respectively.

[0373] In some embodiments, the anti-C2 conjugate comprises a heavy chain and a light chain comprising amino acid sequences having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequences selected from SEQ ID NOs: 71 and 67, respectively, SEQ ID NOs: 72 and 67, respectively, and SEQ ID NOs: 73 and 68, respectively.

[0374] In some embodiments, the anti-C2 conjugate comprises a heavy chain and a light chain comprising the amino acid sequences selected from SEQ ID NOs: 71 and 67, respectively, SEQ ID NOs: 72 and 67, respectively, and SEQ ID NOs: 73 and 68, respectively.

[0375] In some embodiments, herein provided is a conjugate comprising a heavy chain comprising an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to an amino acid sequence selected from SEQ ID NOs: 71-72, 74-78, 85, or111FH13167949.1BPX-0592587, and a light chain comprising an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence of SEQ ID NO: 58.

[0376] In some embodiments, herein provided is a conjugate comprising a heavy chain comprising an amino acid sequence selected from SEQ ID NOs: 71-72, 74-78, 85, or 87, and a light chain comprising the amino acid sequence of SEQ ID NO: 58.

[0377] In some embodiments, herein provided is a conjugate comprising a heavy chain comprising an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to an amino acid sequence selected from SEQ ID NOs: 73, 76-84, 86 or 88, and a light chain comprising an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence of SEQ ID NO: 63.

[0378] In some embodiments, herein provided is a conjugate comprising a heavy chain comprising an amino acid sequence selected from SEQ ID NOs: 73, 76-84, 86, or 88, and a light chain comprising the amino acid sequence of SEQ ID NO: 63.

[0379] In some embodiments, herein provided is a conjugate comprising a heavy chain comprising an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to an amino acid sequence selected from SEQ ID NOs: 73, 86 or 88, and a light chain comprising an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence of SEQ ID NO: 65.

[0380] In some embodiments, herein provided is a conjugate comprising a heavy chain comprising an amino acid sequence selected from SEQ ID NOs: 73, 86 or 88, and a light chain comprising the amino acid sequence of SEQ ID NO: 65.

[0381] In some embodiments, herein provided is a conjugate comprising a heavy chain comprising an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to an amino acid sequence selected from SEQ ID NOs: 72, 73, 83, 86 or 88, and a light chain comprising an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence of SEQ ID NO: 66.

[0382] In some embodiments, herein provided is a conjugate comprising a heavy chain comprising an amino acid sequence selected from SEQ ID NOs: 72, 73, 83, 86 or 88, and a light chain comprising the amino acid sequence of SEQ ID NO: 66.

[0383] In some embodiments, herein provided is a conjugate comprising a heavy chain comprising an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%,112FH13167949.1BPX-0592598%, or 99% identity to an amino acid sequence selected from SEQ ID NOs: 71-72, and a light chain comprising an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence of SEQ ID NO: 67.

[0384] In some embodiments, herein provided is a conjugate comprising a heavy chain comprising an amino acid sequence selected from SEQ ID NOs: 71-72, and a light chain comprising the amino acid sequence of SEQ ID NO: 67.

[0385] In some embodiments, herein provided is a conjugate comprising a heavy chain comprising an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence of SEQ ID NO: 73, and a light chain comprising an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence of SEQ ID NO: 64.

[0386] In some embodiments, herein provided is a conjugate comprising a heavy chain comprising the amino acid sequence of SEQ ID NO: 73, and a light chain comprising the amino acid sequence of SEQ ID NO: 64.Methods of producing anti-C2 conjugates

[0387] The anti-C2 conjugates herein described can be produced using a variety of techniques known in the art of molecular biology and protein chemistry. In some embodiments, the anti-C2 conjugates are produced using substantially similar methods as described herein for producing anti-C2 antibodies. In some embodiments, the anti-C2 conjugates described herein may be made in transformed host cells using recombinant DNA techniques. To do so, a recombinant DNA molecule coding for the anti-C2 conjugate is prepared. Methods of preparing such DNA molecules are well known in the art. For instance, sequences coding for the C2 binding peptide conjugate could be excised from DNA using suitable restriction enzymes.

[0388] Alternatively, the DNA molecule could be synthesized using chemical synthesis techniques, such as the phosphoramidate method. Also, a combination of these techniques could be used.

[0389] The methods of making anti-C2 conjugates also include a vector capable of expressing the anti-C2 conjugates in an appropriate host. The vector comprises the DNA molecule that codes for the anti-C2 conjugate operatively linked to appropriate expression control sequences. Methods of affecting this operative linking, either before or after the DNA molecule is inserted into113FH13167949.1BPX-05925 the vector, are well known. Expression control sequences include promoters, activators, enhancers, operators, ribosomal nuclease domains, start signals, stop signals, cap signals, polyadenylation signals, and other signals involved with the control of transcription or translation.

[0390] The resulting vector having the DNA molecule thereon is used to transform an appropriate host. This transformation may be performed using methods well known in the art.

[0391] Any of a large number of available and well-known host cells may be suitable for use in the methods disclosed herein. The selection of a particular host is dependent upon a number of factors recognized by the art. These include, for example, compatibility with the chosen expression vector, toxicity of the peptides encoded by the DNA molecule, rate of transformation, ease of recovery of the peptides, expression characteristics, bio-safety and costs. A balance of these factors must be struck with the understanding that not all hosts may be equally effective for the expression of a particular DNA sequence. Within these general guidelines, useful microbial hosts include bacteria (such as E. coli sp.), yeast (such as Saccharomyces sp.) and other fungi, insects, plants, mammalian (including human) cells in culture, or other hosts known in the art.

[0392] Next, the transformed host is cultured and purified. Host cells may be cultured under conventional fermentation conditions so that the desired compounds are expressed. Such fermentation conditions are well known in the art. Finally, the peptides are purified from culture by methods well known in the art.

[0393] The compounds may also be made by synthetic methods. For example, solid phase synthesis techniques may be used. Suitable techniques are well known in the art, and include those described in Merrifield (1973), Chem. Polypeptides, pp. 335-61 (Katsoyannis and Panayotis eds.); Merrifield (1963), J. Am. Chem. Soc. 85: 2149; Davis et al. (1985), Biochem. Inti. 10: 394-414; Stewart and Young (1969), Solid Phase Peptide Synthesis; U.S. Pat. No. 3,941,763; Finn et al. (1976), The Proteins (3rd ed.) 2: 105-253; and Erickson et al. (1976), The Proteins (3rd ed.) 2: 257- 527. In some embodiments, solid phase synthesis is a technique for making anti-C2 conjugates. Compounds that contain derivatized peptides or which contain non-peptide groups may be synthesized by well-known organic chemistry techniques.

[0394] In some embodiments, the anti-C2 conjugates may be generated via solid-phase peptide synthesis. In some embodiments, an automated synthesizer or manual solid-phase peptide synthesis techniques are used to synthesize the anti-C2 conjugates. In certain embodiments, solution peptide synthesis may be used to synthesize the anti-C2 conjugates.114FH13167949.1BPX-05925

[0395] In some embodiments, the domains of the anti-C2 conjugate are synthesized as separate units or domains. In some embodiments, the domains of the anti-C2 conjugates are synthesized as a single unit.

[0396] For example, in some embodiments, an anti-C2 conjugate comprising an anti-C2 linked with or without a linker domain to a molecular adjuvant may be synthesized in two separate units, using automated solid-phase peptide synthesis for the anti-C2 and DNA synthesis for the molecular adjuvant (e.g., CpG antigen). The two components may then be coupled in solution via Cu(I)-catalyzed click chemistry. Other methods generally known in the art for solid phase peptide synthesis techniques could be employed to synthesize the anti-C2 component. Other synthetic techniques generally known in the art could be used to synthesize the adjuvant molecule (For example, DNA synthesis variations generally known in the art for the CpG domain and other DNA adjuvants, otherwise varying with the nature of the molecular antigen). Bioconjugation strategies generally known in the art (for example, (amide / NHS ester, sulfhydryl / maleimide, azide / DBCO, and others) could be employed to link the two components of the anti-C2 conjugate.

[0397] In some embodiments, an anti-C2 conjugate comprising an anti-C2 linked with or without a linker domain to an antigen (e.g., a peptide antigen) may be synthesized as a single unit.

[0398] Other methods of molecule expression / synthesis are generally known in the art to one of ordinary skill.

[0399] The nucleic acid molecules described above can be contained within a vector that is capable of directing their expression in, for example, a cell that has been transduced with the vector. Accordingly, expression vectors containing a nucleic acid molecule encoding an anti-C2 conjugate and cells transfected with these vectors are among the certain embodiments.

[0400] Vectors suitable for use include T7-based vectors for use in bacteria (see, for example, Rosenberg et al., Gene 56: 125, 1987), the pMSXND expression vector for use in mammalian cells (Lee and Nathans, J. Biol. Chem. 263:3521, 1988), and baculovirus-derived vectors (for example the expression vector pBacPAKS from Clontech, Palo Alto, Calif.) for use in insect cells. The nucleic acid inserts, which encode the polypeptide of interest in such vectors, can be operably linked to a promoter, which is selected based on, for example, the cell type in which expression is sought. For example, a T7 promoter can be used in bacteria, a polyhedrin promoter can be used in insect cells, and a cytomegalovirus or metallothionein promoter can be used in mammalian cells. Also, in the case of higher eukaryotes, tissue-specific and cell type- specific115FH13167949.1BPX-05925 promoters are widely available. These promoters are so named for their ability to direct expression of a nucleic acid molecule in a given tissue or cell type within the body. Skilled artisans are well aware of numerous promoters and other regulatory elements which can be used to direct expression of nucleic acids.

[0401] In addition to sequences that facilitate transcription of the inserted nucleic acid molecule, vectors can contain origins of replication, and other genes that encode a selectable marker. For example, the neomycin-resistance (neor) gene imparts G418 resistance to cells in which it is expressed, and thus permits phenotypic selection of the transfected cells. Those of skill in the art can readily determine whether a given regulatory element or selectable marker is suitable for use in a particular experimental context.

[0402] Viral vectors that are suitable for use include, for example, retroviral, adenoviral, and adeno-associated vectors, herpes virus, simian virus 40 (SV40), and bovine papilloma virus vectors (see, for example, Gluzman (Ed.), Eukaryotic Viral Vectors, CSH Laboratory Press, Cold Spring Harbor, N.Y.).

[0403] Prokaryotic or eukaryotic cells that contain and express a nucleic acid molecule that encode an anti-C2 conjugate are also suitable for use. A cell is a transfected cell, i.e., a cell into which a nucleic acid molecule, for example a nucleic acid molecule encoding a an anti-C2 conjugate, has been introduced by means of recombinant DNA techniques. The progeny of such a cell are also considered suitable for use in the methods disclosed herein.

[0404] The precise components of the expression system are not critical. For example, an anti-C2 conjugate can be produced in a prokaryotic host, such as the bacterium E. coli, or in a eukaryotic host, such as an insect cell (e.g., an Sf21 cell), or mammalian cells (e.g., CHO cells, COS cells, NIH 3T3 cells, or HeLa cells). These cells are available from many sources, including the American Type Culture Collection (Manassas, Va.). In selecting an expression system, it matters only that the components are compatible with one another. Artisans or ordinary skill are able to make such a determination. Furthermore, if guidance is required in selecting an expression system, skilled artisans may consult Ausubel et al. (Current Protocols in Molecular Biology, John Wiley and Sons, New York, N.Y., 1993) and Pouwels et al. (Cloning Vectors: A Laboratory Manual, 1985 Suppl. 1987).116FH13167949.1BPX-05925

[0405] The expressed an anti-C2 conjugates can be purified from the expression system using routine biochemical procedures, and can be used, e.g., as therapeutic agents, as described herein.Methods of Use

[0406] In some aspects, this disclosure provides methods for treating a complement- associated disease or disorder comprising administering to a subject any of the herein provided anti- C2 antibodies, antigen binding fragments thereof, or any of the herein provided anti-C2 conjugates. In some aspects, the present disclosure provides methods for treating a complement-associated disease or disorder comprising administering to a subject a composition comprising an anti-C2 antibody or antigen binding fragment herein disclosed. In some aspects, the present disclosure provides methods for treating a complement-associated disease or disorder comprising administering to a subject a composition comprising the anti-C2 antibody-conjugate herein disclosed. In some embodiments, the composition comprises a pharmaceutically acceptable carrier. In some embodiments, the composition comprises a pharmaceutically acceptable carrier and the composition further comprises a therapeutically effective amount of an anti-C2 antibody, antigen binding fragments thereof, or an anti-C2 antibody-conjugate as described herein. In some embodiments, the complement-associated disease or disorder is a complement-mediated disease or condition described herein. In some embodiments, the complement-associated disease or disorder is amyotrophic lateral sclerosis (ALS), antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis, atypical hemolytic uremic syndrome (aHUS), aHUS after kidney transplant, autoimmune encephalitis, bullous pemphigoid, C3 glomerulopathy (C3G), C3 glomerulonephritis (C3GN), C3G relapse after kidney transplant, cold agglutinin disease (CAD), CD59 deficiency, CD59-mediated hemolytic anemia with or without immune-mediated polyneuropathy, CHAPLE syndrome (CD55 deficiency), chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), complement Factor I deficiency, diabetic nephropathy, cryoglobulinemia, dense deposit disease, diabetic lumbosacral plexopathy, age-related macular degeneration (AMD), glaucoma, dry AMD, wet AMD, diabetic retinopathy, inherited retinal disease, retinal detachment, familial amyloid polyneuropathy, fibrillary glomerulonephritis, focal segmental glomerulosclerosis (FSGS), geographic atrophy, Goodpasture’s syndrome, Guillain-Barre syndrome, hematopoietic stem cell transplant-associated-thrombotic microangiopathy (HSCT-TMA), hidradenitis suppurativa,117FH13167949.1BPX-05925Huntington's disease, IgA nephropathy (IgAN), IGAN relapse after kidney transplant antibody mediated rejection (i.e., kidney transplant) post-transplant rejection (solid organ antibody mediated rejection), immune complex membranoproliferative glomerulonephritis (IC-MPGN), immune- mediated necrotizing myopathy, immunoglobulin A-associated vasculitis (IgAV), immunoglobulin A-associated vasculitis (IgAV) nephritis, immune thrombocytopenia (ITP), immune thrombocytopenic purpura, lupus nephritis, lupus nephritis flares with high urinary Ba or sCb5 -9, multiple sclerosis, multifocal motor neuropathy (MMN), myasthenia gravis, neuromyelitis optica spectrum disorder (NMOSD), paroxysmal nocturnal hemoglobinuria (PNH), post-infectious glomerulonephritis, primary membranous nephropathy (PMN), rhabdomyolysis-induced acute kidney injury (RIAKI), sickle cell disease, Sjogren's syndrome, tauopathy, thrombotic microangiopathy (TMA), systemic lupus erythematosus, thrombotic thrombocytopenic purpura (TTP), warm autoimmune hemolytic anemia (WAHA), acute spinal cord injuries, anti-MAG (myelin-associated glycoprotein) peripheral polyneuropathy (IgM neuropathy), pyoderma gangrenosum, dermatomyositis, hypocomplementemic urticarial vasculitis syndrome (HUVS), auto-immune chronic spontaneous urticaria (aiCUS), Kawasaki disease, Takayasu's arteritis, antiphospholipid therapy - thrombosis prevention (antiphospholipid syndrome), catastrophic antiphospholipid syndrome (CAPS), pre-eclampsia, HELLP syndrome, and autoimmune hepatitis (AH).

[0407] In some embodiments, the complement-associated disease or disorder is selected from acute spinal cord injuries, CIDP, NMOSD, GBS, MMN, and IgM neuropathy. In some embodiments, the complement-associated disease or disorder is selected from delayed graft function (i.e., kidney transplant), Goodpasture's Syndrome, and C3G. In some embodiments, the complement-associated disease or disorder is selected from hidradenitis suppurativa, bullous pemphigoid, IgA Vasculitis, pyoderma gangrenosum, and dermatomyositis. In some embodiments, the complement-associated disease or disorder is selected from myasthenia gravis, Behcet's disease, IgG4-related disease, HSCT-TMA, IMNM, HUVS, aiCSU, Kawasaki disease, and Takayasu's arteritis. In some embodiments, the complement-associated disease or disorder is selected from antiphospholipid syndrome, CAD, CAPS, wAIHA, WAHA, post-transplant rejection (solid organ antibody mediated rejection), and antibody mediated rejection (i.e., kidney transplant). In some embodiments, the complement-associated disease or disorder is selected from dermatomyositis or118FH13167949.1BPX-05925MMN. In some embodiments, the complement-associated disease or disorder is selected from bullous pemphigoid or HUVS.

[0408] The above-described anti-C2antibodies, antigen binding fragments thereof, or anti- C2 antibody-conjugates are useful in, inter alia, methods for treating or preventing a variety of complement related diseases or disorders in a subject. The anti-C2 antibodies or anti-C2 conjugates can be administered to a subject, e.g., a human subject, using a variety of methods that depend, in part, on the route of administration. The route can be, e.g., intravenous injection or infusion (IV), subcutaneous injection (SC), intraperitoneal (IP) injection, intramuscular injection (IM), or intrathecal injection (IT). The injection / infusion can be in a bolus or a continuous infusion. In certain embodiments, the route of administration is intravenous injection or infusion (IV), which can be administered in a bolus or a continuous infusion. In certain embodiments, the route of administration is subcutaneous injection (SC).

[0409] Administration can be achieved by, e.g., local infusion, injection, or by means of an implant. The composition can be delivered to the subject by way of an implantable device based on, e.g., diffusive, erodible, or convective systems, e.g., osmotic pumps, biodegradable implants, electro diffusion systems, electroosmosis systems, vapor pressure pumps, electrolytic pumps, effervescent pumps, piezoelectric pumps, erosion-based systems, or electromechanical systems.

[0410] In some embodiments, an anti-C2 antibody, antigen-binding fragment thereof, or an anti-C2 antibody-peptide conjugate is therapeutically delivered to a subject by way of local administration.

[0411] As described above, a composition comprising an anti-C2 antibody, or antigen binding fragment thereof, or an anti-C2 antibody-conjugated described herein (e.g., anti-C2 compositions) can be used to treat a variety of complement-associated diseases or disorders such as but not limited to: amyotrophic lateral sclerosis (ALS), antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis, atypical hemolytic uremic syndrome (aHUS), aHUS after kidney transplant, autoimmune encephalitis, bullous pemphigoid, C3 glomerulopathy (C3G), C3 glomerulonephritis (C3GN), C3G relapse after kidney transplant, cold agglutinin disease (CAD), CD59 deficiency, CD59-mediated hemolytic anemia with or without immune-mediated polyneuropathy, CHAPLE syndrome (CD55 deficiency), chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), complement Factor I deficiency, diabetic nephropathy, cryoglobulinemia, dense deposit disease, diabetic lumbosacral plexopathy, age-related macular119FH13167949.1BPX-05925 degeneration (AMD), glaucoma, dry AMD, wet AMD, diabetic retinopathy, inherited retinal disease, retinal detachment, familial amyloid polyneuropathy, fibrillary glomerulonephritis, focal segmental glomerulosclerosis (FSGS), geographic atrophy, Goodpasture’s syndrome, Guillain- Barre syndrome, hematopoietic stem cell transplant-associated-thrombotic microangiopathy (HSCT-TMA), hidradenitis suppurativa, Huntington's disease, IgA nephropathy (IgAN), IGAN relapse after kidney transplant antibody mediated rejection (i.e., kidney transplant) post-transplant rejection (solid organ antibody mediated rejection), immune complex membranoproliferative glomerulonephritis (IC-MPGN), immune-mediated necrotizing myopathy, immunoglobulin A- associated vasculitis (IgAV), immunoglobulin A-associated vasculitis (IgAV) nephritis, immune thrombocytopenia (ITP), immune thrombocytopenic purpura, lupus nephritis, lupus nephritis flares with high urinary Ba or sCb5 -9, multiple sclerosis, multifocal motor neuropathy (MMN), myasthenia gravis, neuromyelitis optica spectrum disorder (NMOSD), paroxysmal nocturnal hemoglobinuria (PNH), post-infectious glomerulonephritis, primary membranous nephropathy (PMN), rhabdomyolysis-induced acute kidney injury (RIAKI), sickle cell disease, Sjogren's syndrome, tauopathy, thrombotic microangiopathy (TMA), systemic lupus erythematosus, thrombotic thrombocytopenic purpura (TTP), warm autoimmune hemolytic anemia (WAHA), acute spinal cord injuries, anti-MAG (myelin-associated glycoprotein) peripheral polyneuropathy (IgM neuropathy), pyoderma gangrenosum, dermatomyositis, hypocomplementemic urticarial vasculitis syndrome (HUVS), auto-immune chronic spontaneous urticaria (aiCUS), Kawasaki disease, Takayasu's arteritis, antiphospholipid therapy - thrombosis prevention (antiphospholipid syndrome), catastrophic antiphospholipid syndrome (CAPS), pre-eclampsia, HELLP syndrome, and autoimmune hepatitis (AIH).

[0412] In certain embodiments, the complement-associated disease or disorder is selected from CAD, aHUS, IgAN, and lupus nephritis (LN).

[0413] In certain embodiments, the anti-C2 compositions described herein are used to treat a subject suffering from a complement-associated neurological disease or disorder. In certain embodiments, such complement-associated neurological disease or disorder is selected from the group consisting of acute spinal cord injuries, CIDP, NMOSD, GBS, MMN, and IgM neuropathy. In certain embodiments, such complement-associated neurological disease or disorder is selected from the group consisting of acute spinal cord injuries, GBS, and MMN.120FH13167949.1BPX-05925

[0414] In certain embodiments, the anti-C2 compositions described herein are used to treat a subject suffering from a complement-associated nephrology disease or disorder. In certain embodiments, complement-associated nephrology disease or disorder is selected from the group consisting of delayed graft function (i.e., kidney transplant), Goodpasture's Syndrome, and C3G.

[0415] In certain embodiments, the anti-C2 compositions described herein are used to treat a subject suffering from a complement-associated dermatological disease or disorder. In certain embodiments, complement-associated dermatological disease or disorder is selected from the group consisting of hidradenitis suppurativa, bullous pemphigoid, IgA Vasculitis, pyoderma gangrenosum, and dermatomyositis. In certain embodiments, complement-associated dermatological disease or disorder is bullous pemphigoid or dermatomyositis.

[0416] In certain embodiments, the anti-C2 compositions described herein are used to treat a subject suffering from a complement-associated immunological disease or disorder. In certain embodiments, complement-associated immunological disease or disorder is selected from the group consisting of myasthenia gravis, Behcet's disease, IgG4-related disease, HSCT-TMA, IMNM, HUVS, aiCSU, Kawasaki disease, and Takayasu's arteritis. In certain embodiments, complement- associated immunological disease or disorder is selected from the group consisting of IgG4-related disease, HSCT-TMA, IMNM, and HUVS.

[0417] In certain embodiments, the anti-C2 compositions described herein are used to treat a subject suffering from a complement-associated hematological disease or disorder. In certain embodiments, complement-associated hematological disease or disorder is selected from the group consisting of antiphospholipid syndrome, CAD, CAPS, wAIHA, WAHA, post-transplant rejection (solid organ antibody mediated rejection), and antibody mediated rejection (i.e., kidney transplant) In certain embodiments, the anti-C2 compositions described herein are used to treat a subject suffering from complement-associated obstetrics / gynecological disease or disorder. In certain embodiments, complement-associated obstetrics / gynecological disease or disorder is selected from the group consisting of pre-eclampsia and HELLP Syndrome. In certain embodiments, complement- associated obstetrics / gynecological disease or disorder is HELLP Syndrome.

[0418] In certain embodiments, a composition comprising an anti-C2 antibody, or antigen binding fragments thereof, as described herein is used to treat a subject suffering from dermatomyositis or MMN. In certain embodiment, such a composition may further comprise a pharmaceutically acceptable carrier.121FH13167949.1BPX-05925

[0419] In certain embodiments, a composition comprising an anti-C2 antibody conjugate as described herein is used to treat a subject suffering from bullous pemphigoid or HUVS. In certain embodiment, such a composition may further comprise a pharmaceutically acceptable carrier.

[0420] In some embodiments, the anti-C2 antibodies, fragments thereof, or the anti-C2 conjugates, reduce the formation of the MAC by at least 5%, at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 35%, at least 40%, at least 45%, at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 100%, at least 105%, at least 110%, at least 115%, at least 120%, at least 125%, at least 130%, at least 135%, at least 140%, at least 145%, or at least 150%.

[0421] In some embodiments, the present disclosure provides a nucleic acid comprising a nucleotide encoding the VL, the VH, the heavy chain, the light chain, or any combination thereof, of the antibody or antigen binding fragment. In some embodiments, the nucleic acid comprises a nucleotide sequence encoding the conjugate of any herein disclosed.

[0422] In some embodiments, the present disclosure provides an expression vector. In some embodiments, the present disclosure provides a cell comprising the expression vector as herein disclosed.Kits

[0423] In some embodiments, the disclosure provides a kit comprising an anti-C2 antibody, or antigen binding fragment thereof, described herein. In some embodiments, the disclosure provides a kit comprising an anti-C2 antibody conjugate as described herein. In some embodiments, a kit includes an anti-C2 antibody, or antigen binding fragment thereof, and / or an anti-C2 antibodyconjugates as disclosed herein, and instructions for use. The kits may comprise, in a suitable container, an anti-C2 antibody, or antigen binding fragment thereof, one or more controls, and various buffers, reagents, enzymes and other standard ingredients well known in the art.

[0424] The container can include at least one vial, well, test tube, flask, bottle, syringe, or other container means, into which an anti-C2 antibody, or antigen binding fragment thereof, or an anti-C2 antibody-conjugate may be placed, and in some instances, suitably aliquoted. Where an additional component is provided, the kit can contain additional containers into which this component may be placed. The kits can also include a means for containing an anti-C2 antibody, or antigen binding fragment thereof, or an anti-C2 antibody-conjugate, and any other reagent122FH13167949.1BPX-05925 containers in close confinement for commercial sale. Such containers may include injection or blow-molded plastic containers into which the desired vials are retained. Containers and / or kits can include labeling with instructions for use and / or warnings.

[0425] In some embodiments, a kit comprises a container comprising an anti-C2 antibody, or antigen binding fragment thereof, or an anti-C2 antibody-conjugate and a pharmaceutically acceptable carrier, or a pharmaceutical composition comprising the anti-C2 antibody, or antigen binding fragment thereof, or an anti-C2 antibody-conjugate, and instructions for treating a complement-mediated disease or condition described herein in a subject in need thereof. In some embodiments, a kit comprises a container comprising an anti-C2 antibody, or antigen binding fragment thereof, or an anti-C2 antibody-conjugate, and a pharmaceutically acceptable carrier, or a pharmaceutical composition comprising the anti-C2 antibody, or antigen binding fragment thereof, or an anti-C2 antibody-conjugate, and a package insert comprising instructions for administering the anti-C2 antibody, or antigen binding fragment thereof, or an anti-C2 antibody-conjugate, to a subject in need thereof, alone or in combination with another agent, for treating or delaying progression of a complement-associated disease or condition as described herein in the subject.EXEMPLARY EMBODIMENTS

[0426] Exemplary Embodiment 1. An antibody, or antigen binding fragment thereof, that specifically binds complement component C2 (C2), wherein the antibody or antigen binding fragment comprises a light chain variable region (VL) and a heavy chain variable region (VH), wherein the VL comprises a VL complementarity determining region (CDR) 1 (CDRL1) set forth in SEQ ID NO: 1 (XsTFTDIDDDMN), a VL CDR2 (CDRL2) set forth in SEQ ID NO: 2 (EGNTLRP), and a VL CDR 3 (CDRL3) set forth in SEQ ID NO: 3 (X9QSDNLPFT), and the VH comprises a VH CDR 1 (CDRH1) set forth in SEQ ID NO: 4 (GYTFTDYNMH), a VH CDR 2 (CDRH2) set forth in SEQ ID NO: 5 (YVYPX5IGGTG), and a VH CDR 3 (CDRH3) set forth in SEQ ID NO: 6 (RGYX10GIFDY), wherein X8is I or R; X9is L or Q; X5is Y or S; and X10 is D or E, and wherein at least one of X9 is Q, X5 is S, and X10 is E.

[0427] Exemplary Embodiment 2. The antibody or antigen binding fragment of Exemplary Embodiment 1, wherein (i) the CDRL1 is set forth in SEQ ID NO: 8 (RTFTDIDDDMN), the CDRL3 is set forth in SEQ ID NO: 9 (LQSDNLPFT), the CDRH2 is set forth in SEQ ID NO: 11 (YVYPYIGGTG), and the CDRH3 is set forth in SEQ ID NO: 14 (RGYEGIFDY); (11) the CDRL1123FH13167949.1BPX-05925 is set forth in SEQ ID NO: 8, the CDRL3 is set forth in SEQ ID NO: 9, the CDRH2 is set forth in SEQ ID NO: 12 (YVYPSIGGTG), and the CDRH3 is set forth in SEQ ID NO: 13 (RGYDGIFDY); (hi) the CDRL1 is set forth in SEQ ID NO: 8, the CDRL3 is set forth in SEQ ID NO: 9, the CDRH2 is set forth in SEQ ID NO: 12, and the CDRH3 is set forth in SEQ ID NO: 14; (iv) the CDRL1 is set forth in SEQ ID NO: 8, the CDRL3 is set forth in SEQ ID NO: 10 (QQSDNLPFT), the CDRH2 is set forth in SEQ ID NO: 12, and the CDRH3 is set forth in SEQ ID NO: 14; (v) the CDRL1 is set forth in SEQ ID NO: 7 (ITFTDIDDDMN), the CDRL3 is set forth in SEQ ID NO: 9, the CDRH2 is set forth in SEQ ID NO: 12, and the CDRH3 is set forth in SEQ ID NO: 14; (vi) the CDRL1 is set forth in SEQ ID NO: 7, the CDRL3 is set forth in SEQ ID NO: 9, the CDRH2 is set forth in SEQ ID NO: 11, and the CDRH3 is set forth in SEQ ID NO: 14; (vh) the CDRL1 is set forth in SEQ ID NO: 7, the CDRL3 is set forth in SEQ ID NO: 9, the CDRH2 is set forth in SEQ ID NO: 12, and the CDRH3 is set forth in SEQ ID NO: 13; (vm) the CDRL1 is set forth in SEQ ID NO: 7, the CDRL3 is set forth in SEQ ID NO: 10, the CDRH2 is set forth in SEQ ID NO: 12, and the CDRH3 is set forth in SEQ ID NO: 14; or (ix) the CDRL1 is set forth in SEQ ID NO: 7, the CDRL3 is set forth in SEQ ID NO: 10, the CDRH2 is set forth in SEQ ID NO: 12, and the CDRH3 is set forth in SEQ ID NO: 13.

[0428] Exemplary Embodiment 3. The antibody or antigen binding fragment of Exemplary Embodiments 1 or 2, wherein the VL comprises at least one VL framework region (FR) selected from SEQ ID Nos: 15-18.

[0429] Exemplary Embodiment 4. The antibody or antigen binding fragment of any one of Exemplary Embodiments 1-3, wherein the VL comprises a FR1 region selected from SEQ ID NOs: 23, 24, 25, 26, and 27, a FR2 region selected from SEQ ID NOs: 28 and 29, a FR3 region selected from SEQ ID NOs: 30, 31, and 32, and a FR4 region set forth in SEQ ID NO: 18.

[0430] Exemplary Embodiment 5. The antibody or antigen binding fragment of any one of Exemplary Embodiments 1-4, wherein the VL comprises a FR1 region set forth in SEQ ID NO: 23, a FR2 region set forth in SEQ ID NO: 28, a FR3 region set forth in SEQ ID NO: 30, and a FR4 region set forth in SEQ ID NO: 18.

[0431] Exemplary Embodiment 6. The antibody or antigen binding fragment of any one of Exemplary Embodiments 1-4, wherein the VL comprises a FR1 region set forth in SEQ ID NO: 24, a FR2 region set forth in SEQ ID NO: 28, a FR3 region set forth in SEQ ID NO: 30, and a FR4 region set forth in SEQ ID NO: 18.124FH13167949.1BPX-05925

[0432] Exemplary Embodiment 7. The antibody or antigen binding fragment of any one of Exemplary Embodiments 1-4, wherein the VL comprises a FR1 region set forth in SEQ ID NO: 24, a FR2 region set forth in SEQ ID NO: 29, a FR3 region set forth in SEQ ID NO: 31, and a FR4 region set forth in SEQ ID NO: 18.

[0433] Exemplary Embodiment 8. The antibody or antigen binding fragment of any one of Exemplary Embodiments 1-4, wherein the VL comprises a FR1 region set forth in SEQ ID NO: 24, a FR2 region set forth in SEQ ID NO: 29, a FR3 region set forth in SEQ ID NO: 32, and a FR4 region set forth in SEQ ID NO: 18.

[0434] Exemplary Embodiment 9. The antibody or antigen binding fragment of any one of Exemplary Embodiments 1-8, wherein the VH comprises at least one VH FR selected from SEQ ID NOs: 19-22.

[0435] Exemplary Embodiment 10. The antibody or antigen binding fragment of any one of Exemplary Embodiments 1-9, wherein the VH comprises a FR1 region selected from SEQ ID NOs: 33 and 34, a FR2 region set forth in SEQ ID NO: 20, a FR3 region set forth in SEQ ID NO: 21, and a FR4 region set forth in SEQ ID NO: 22.

[0436] Exemplary Embodiment 11. The antibody or antigen binding fragment of any one of Exemplary Embodiments 1-7 and 9-10, wherein the VH comprises a FR1 region set forth in SEQ ID NO: 33, a FR2 region set forth in SEQ ID NO: 20, a FR3 region set forth in SEQ ID NO: 21, and a FR4 region set forth in SEQ ID NO: 22.

[0437] Exemplary Embodiment 12. The antibody or antigen binding fragment of any one of Exemplary Embodiments 1-4 and 9-10, wherein the VH comprises a FR1 region set forth in SEQ ID NO: 34, a FR2 region set forth in SEQ ID NO: 20, a FR3 region set forth in SEQ ID NO: 21, and a FR4 region set forth in SEQ ID NO: 22.

[0438] Exemplary Embodiment 13. The antibody or antigen binding fragment of any one of Exemplary Embodiments 1-12, wherein the VH and the VL comprise amino acid sequences having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequences selected from (a) SEQ ID NOs: 36 and 50, respectively; (b) SEQ ID NOs: 37 and 50, respectively; (c) SEQ ID NOs: 38 and 50, respectively; (d) SEQ ID NOs: 38 and 51, respectively;(e) SEQ ID NOs: 38 and 52, respectively; (f) SEQ ID NOs: 36 and 40, respectively; (g) SEQ ID NOs: 36 and 41, respectively; (h) SEQ ID NOs: 36 and 42, respectively; (i) SEQ ID NOs: 36 and 43, respectively; (j) SEQ ID NOs: 36 and 44, respectively; (k) SEQ ID NOs: 37 and 40,125FH13167949.1BPX-05925 respectively; (1) SEQ ID NOs: 38 and 40, respectively; (m) SEQ ID NOs: 38 and 41, respectively; (n) SEQ ID NOs: 38 and 45, respectively; (o) SEQ ID NOs: 38 and 46, respectively; (p) SEQ ID NOs: 38 and 47, respectively; (q) SEQ ID NOs: 38 and 48, respectively; (r) SEQ ID NOs: 37 and 46, respectively; and (s) SEQ ID NOs: 37 and 48, respectively.

[0439] Exemplary Embodiment 14. The antibody or antigen binding fragment of any one of Exemplary Embodiments 1-12, wherein the VH and the VL comprise the amino acid sequences selected from (a) SEQ ID NOs: 36 and 50, respectively; (b) SEQ ID NOs: 37 and 50, respectively; (c) SEQ ID NOs: 38 and 50, respectively; (d) SEQ ID NOs: 38 and 51, respectively; (e) SEQ ID NOs: 38 and 52, respectively; (f) SEQ ID NOs: 36 and 40, respectively; (g) SEQ ID NOs: 36 and 41, respectively; (h) SEQ ID NOs: 36 and 42, respectively; (i) SEQ ID NOs: 36 and 43, respectively; (j) SEQ ID NOs: 36 and 44, respectively; (k) SEQ ID NOs: 37 and 40, respectively; (1) SEQ ID NOs: 38 and 40, respectively; (m) SEQ ID NOs: 38 and 41, respectively; (n) SEQ ID NOs: 38 and 45, respectively; (o) SEQ ID NOs: 38 and 46, respectively; (p) SEQ ID NOs: 38 and 47, respectively; (q) SEQ ID NOs: 38 and 48, respectively; (r) SEQ ID NOs: 37 and 46, respectively; and (s) SEQ ID NOs: 37 and 48, respectively.

[0440] Exemplary Embodiment 15. An antibody, or antigen binding fragment thereof, that specifically binds complement component 2 (C2), wherein the antibody or antigen binding fragment comprises (i) a VL comprising (a) a CDRL1 set forth in SEQ ID NO: 1 (XsTFTDIDDDMN), wherein Xi is I or R; (b) a CDRL2 set forth in SEQ ID NO: 2 (EGNTLRP); (c) a CDRL3 set forth in SEQ ID NO: 3 (X9QSDNLPFT), wherein X9 is L or Q; (d) a VL FR1 comprising an amino acid sequence having at least 95% identity to SEQ ID NO: 15 (ETTVTQSPSSLSX11SVGX12RVTIX13C), wherein Xu is M or A; X12 is D or E; X13 is T or R; (e) a VL FR2 comprising an amino acid sequence having at least 95% identity to SEQ ID NO: 16 (WYQQKPGKXigPKLLIS), wherein Xi6 is P or A; (f) a VL FR3 comprising an amino acid sequence having at least 95% identity to SEQ ID NO: 17 (GVPSRFSXI8SG¥GTDFTFTISSMQPEDXI9ATYYC), wherein Xi8is S or G; X19 is V or F; and (g) a VL FR4 comprising an amino acid sequence having at least 95% identity to SEQ ID NO: 18 (FGQGTKLEIK); and (11) a VH comprising (A) a CDRH1 set forth in SEQ ID NO: 4 (GYTFTDYNMH); (B) a CDRH2 set forth in SEQ ID NO: 5 (YVYPX5IGGTG), wherein X5is Y or S; (C) a CDRH3 set forth in SEQ ID NO: 6 (RGYX10GIFDY), wherein X10 is D or E; (D) a VH FR1 comprising an amino acid sequence having at least 95% identity to SEQ ID NO: 19126FH13167949.1BPX-05925(X20VQLVQSGAEVKKPGASVKISCKAS), wherein X20is E or Q; (E) a VH FR2 comprising an amino acid sequence having at least 95% identity to SEQ ID NO: 20 (WVRQAPGQGLEWIG); (F) a VH FR3 comprising an amino acid sequence having at least 95% identity to SEQ ID NO: 21 (YNQKFKNRATLTVDTSTSTAYMELSSLRSEDTAVYYCTR); and (G) a VH FR4 comprising an amino acid sequence having at least 95% identity to SEQ ID NO: 22 (WGQGTTLTVSS).

[0441] Exemplary Embodiment 16. The antibody or antigen binding fragment of Exemplary Embodiment 15, wherein (a) the CDRL1 set forth in SEQ ID NO: 7 (ITFTDIDDDMN); (c) the CDRL3 set forth in SEQ ID NO: 9 (LQSDNLPFT); (d) the VL FR1 set forth in SEQ ID NO: 23 (ETTVTQSPSSLSMSVGDRVTITC); (e) the VL FR2 set forth in SEQ ID NO: 28 (WYQQKPGKPPKLLIS); (f) the VL FR3 set forth in SEQ ID NO: 30 (GVPSRFSSSGYGTDFTFTISSMQPEDVATYYC); and (g) the VL FR4 set forth in SEQ ID NO: 18; and (h) the VH comprises (B) the CDRH2 set forth in SEQ ID NO: 11 (YVYPYIGGTG); (C) the CDRH3 set forth in SEQ ID NO: 13 (RGYDGIFDY); (D) the VH FR1 set forth in SEQ ID NO: 33 (EVQLVQSGAEVKKPGASVKISCKAS); (E) the VH FR2 set forth in SEQ ID NO: 20; (F) the VH FR3 set forth in SEQ ID NO: 21; and (G) the VH FR4 set forth in SEQ ID NO: 22.

[0442] Exemplary Embodiment 17. The antibody or antigen binding fragment of Exemplary Embodiment 15, wherein (i) the VL comprises (a) the CDRL1 set forth in SEQ ID NO: 7; (c) the CDRL3 set forth in SEQ ID NO: 9; (d) the VL FR1 set forth in SEQ ID NO: 23; (e) the VL FR2 set forth in SEQ ID NO: 28; (f) the VL FR3 set forth in SEQ ID NO: 30; and (g) the VL FR4 set forth in SEQ ID NO: 18; and (ii) the VH comprises (B) the CDRH2 set forth in SEQ ID NO: 11 ; (C) the CDRH3 set forth in SEQ ID NO: 13; (D) the VH FR1 set forth in SEQ ID NO: 34 (QVQLVQSGAEVKKPGASVKISCKAS); (E) the VH FR2 set forth in SEQ ID NO: 20; (F) the VH FR3 set forth in SEQ ID NO: 21; and (G) the VH FR4 set forth in SEQ ID NO: 22.

[0443] Exemplary Embodiment 18. The antibody or antigen binding fragment of Exemplary Embodiment 15, wherein (i) the VL comprises (a) the CDRL1 set forth in SEQ ID NO: 7; (c) the CDRL3 set forth in SEQ ID NO: 9; (d) the VL FR1 set forth in SEQ ID NO: 24 (ETTVTQSPSSLSASVGDRVTITC); (e) the VL FR2 set forth in SEQ ID NO: 29 (WYQQKPGKAPKLLIS); (f) the VL FR3 set forth in SEQ ID NO: 31 (GVPSRFSSSGYGTDFTFTISSMQPEDFATYYC); and (g) the VL FR4 set forth in SEQ ID NO: 18; and (ii) the VH comprises (B) the CDRH2 set forth in SEQ ID NO: 11; (C) the CDRH3 set forth in SEQ ID NO: 13; (D) the VH FR1 set forth in SEQ ID NO: 33; (E) the VH FR2 set forth in SEQ127FH13167949.1BPX-05925ID NO: 20; (F) the VH FR3 set forth in SEQ ID NO: 21; and (G) the VH FR4 set forth in SEQ ID NO: 22.

[0444] Exemplary Embodiment 19. The antibody or antigen binding fragment of Exemplary Embodiment 15, wherein (i) the VL comprises (a) the CDRL1 set forth in SEQ ID NO: 8 (RTFTDIDDDMN); (c) the CDRL3 set forth in SEQ ID NO: 9; (d) the VL FR1 set forth in SEQ ID NO: 24; (e) the VL FR2 set forth in SEQ ID NO: 29; (f) the VL FR3 set forth in SEQ ID NO: 32 (GVPSRFSGSGYGTDFTFTISSMQPEDFATYYC); and (g) the VL FR4 set forth in SEQ ID NO: 18; and (ii) the VH comprises (B) the CDRH2 set forth in SEQ ID NO: 11; (C) the CDRH3 set forth in SEQ ID NO: 13; (D) the VH FR1 set forth in SEQ ID NO: 33; (E) the VH FR2 set forth in SEQ ID NO: 20; (F) the VH FR3 set forth in SEQ ID NO: 21; and (G) the VH FR4 set forth in SEQ ID NO: 22.

[0445] Exemplary Embodiment 20. The antibody or antigen binding fragment of ExemplaryEmbodiment 15, wherein (i) the VL comprises (a) the CDRL1 set forth in SEQ ID NO: 8; (c) the CDRL3 set forth in SEQ ID NO: 9; (d) the VL FR1 set forth in SEQ ID NO: 23; (e) the VL FR2 set forth in SEQ ID NO: 28; (f) the VL FR3 set forth in SEQ ID NO: 30; and (g) the VL FR4 set forth in SEQ ID NO: 18; and (ii) the VH comprises (B) the CDRH2 set forth in SEQ ID NO: 11 ; (C) the CDRH3 set forth in SEQ ID NO: 13; (D) the VH FR1 set forth in SEQ ID NO: 33; (E) the VH FR2 set forth in SEQ ID NO: 20; (F) the VH FR3 set forth in SEQ ID NO: 21; and (G) the VH FR4 set forth in SEQ ID NO: 22.

[0446] Exemplary Embodiment 21. The antibody or antigen binding fragment of ExemplaryEmbodiment 15, wherein (i) the VL comprises (a) the CDRL1 set forth in SEQ ID NO: 8; (c) the CDRL3 set forth in SEQ ID NO: 9; (d) the VL FR1 set forth in SEQ ID NO: 24; (e) the VL FR2 set forth in SEQ ID NO: 29; (f) the VL FR3 set forth in SEQ ID NO: 32; and (g) the VL FR4 set forth in SEQ ID NO: 18; and (ii) the VH comprises (B) the CDRH2 set forth in SEQ ID NO: 11 ; (C) the CDRH3 set forth in SEQ ID NO: 14; (D) the VH FR1 set forth in SEQ ID NO: 33; (E) the VH FR2 set forth in SEQ ID NO: 20; (F) the VH FR3 set forth in SEQ ID NO: 21; and (G) the VH FR4 set forth in SEQ ID NO: 22.

[0447] Exemplary Embodiment 22. The antibody or antigen binding fragment of ExemplaryEmbodiment 15, wherein (i) the VL comprises (a) the CDRL1 set forth in SEQ ID NO: 8; (c) the CDRL3 set forth in SEQ ID NO: 9; (d) the VL FR1 set forth in SEQ ID NO: 24; (e) the VL FR2 set forth in SEQ ID NO: 29; (f) the VL FR3 set forth in SEQ ID NO: 32; and (g) the VL FR4 set forth128FH13167949.1BPX-05925 in SEQ ID NO: 18; and (ii) the VH comprises (B) the CDRH2 set forth in SEQ ID NO: 12; (C) the CDRH3 set forth in SEQ ID NO: 13; (D) the VH FR1 set forth in SEQ ID NO: 33; (E) the VH FR2 set forth in SEQ ID NO: 20; (F) the VH FR3 set forth in SEQ ID NO: 21; and (G) the VH FR4 set forth in SEQ ID NO: 22.

[0448] Exemplary Embodiment 23. The antibody or antigen binding fragment of Exemplary Embodiment 15, wherein (i) the VL comprises (a) the CDRL1 set forth in SEQ ID NO: 8; (c) the CDRL3 set forth in SEQ ID NO: 9; (d) the VL FR1 set forth in SEQ ID NO: 24; (e) the VL FR2 set forth in SEQ ID NO: 29; (f) the VL FR3 set forth in SEQ ID NO: 32; and (g) the VL FR4 set forth in SEQ ID NO: 18; and (ii) the VH comprises (B) the CDRH2 set forth in SEQ ID NO: 12; (C) the CDRH3 set forth in SEQ ID NO: 14; (D) the VH FR1 set forth in SEQ ID NO: 33; (E) the VH FR2 set forth in SEQ ID NO: 20; (F) the VH FR3 set forth in SEQ ID NO: 21; and (G) the VH FR4 set forth in SEQ ID NO: 22.

[0449] Exemplary Embodiment 24. The antibody or antigen binding fragment of Exemplary Embodiment 15, wherein (i) the VL comprises (a) the CDRL1 set forth in SEQ ID NO: 8; (c) the CDRL3 set forth in SEQ ID NO: 10; (d) the VL FR1 set forth in SEQ ID NO: 24; (e) the VL FR2 set forth in SEQ ID NO: 29; (f) the VL FR3 set forth in SEQ ID NO: 32; and (g) the VL FR4 set forth in SEQ ID NO: 18; and (ii) the VH comprises (B) the CDRH2 set forth in SEQ ID NO: 12; (C) the CDRH3 set forth in SEQ ID NO: 14; (D) the VH FR1 set forth in SEQ ID NO: 33; (E) the VH FR2 set forth in SEQ ID NO: 20; (F) the VH FR3 set forth in SEQ ID NO: 21; and (G) the VH FR4 set forth in SEQ ID NO: 22.

[0450] Exemplary Embodiment 25. The antibody or antigen binding fragment of Exemplary Embodiment 15, wherein (i) the VL comprises (a) the CDRL1 set forth in SEQ ID NO: 7; (c) the CDRL3 set forth in SEQ ID NO: 9; (d) the VL FR1 set forth in SEQ ID NO: 24; (e) the VL FR2 set forth in SEQ ID NO: 29; (f) the VL FR3 set forth in SEQ ID NO: 32; and (g) the VL FR4 set forth in SEQ ID NO: 18; and (ii) the VH comprises (B) the CDRH2 set forth in SEQ ID NO: 12; (C) the CDRH3 set forth in SEQ ID NO: 14; (D) the VH FR1 set forth in SEQ ID NO: 33; (E) the VH FR2 set forth in SEQ ID NO: 20; (F) the VH FR3 set forth in SEQ ID NO: 21; and (G) the VH FR4 set forth in SEQ ID NO: 22.

[0451] Exemplary Embodiment 26. The antibody or antigen binding fragment of Exemplary Embodiment 15, wherein (i) the VL comprises (a) the CDRL1 set forth in SEQ ID NO: 7; (c) the CDRL3 set forth in SEQ ID NO: 9; (d) the VL FR1 set forth in SEQ ID NO: 23; (e) the VL FR2 set129FH13167949.1BPX-05925 forth in SEQ ID NO: 28; (f) the VL FR3 set forth in SEQ ID NO: 30; and (g) the VL FR4 set forth in SEQ ID NO: 18; and (ii) the VH comprises (B) the CDRH2 set forth in SEQ ID NO: 11 ; (C) the CDRH3 set forth in SEQ ID NO: 14; (D) the VH FR1 set forth in SEQ ID NO: 33; (E) the VH FR2 set forth in SEQ ID NO: 20; (F) the VH FR3 set forth in SEQ ID NO: 21; and (G) the VH FR4 set forth in SEQ ID NO: 22.

[0452] Exemplary Embodiment 27. The antibody or antigen binding fragment of Exemplary Embodiment 15, wherein (i) the VL comprises (a) the CDRL1 set forth in SEQ ID NO: 8; (c) the CDRL3 set forth in SEQ ID NO: 9; (d) the VL FR1 set forth in SEQ ID NO: 23; (e) the VL FR2 set forth in SEQ ID NO: 28; (f) the VL FR3 set forth in SEQ ID NO: 30; and (g) the VL FR4 set forth in SEQ ID NO: 18; and (ii) the VH comprises (B) the CDRH2 set forth in SEQ ID NO: 11 ; (C) the CDRH3 set forth in SEQ ID NO: 14; (D) the VH FR1 set forth in SEQ ID NO: 33; (E) the VH FR2 set forth in SEQ ID NO: 20; (F) the VH FR3 set forth in SEQ ID NO: 21; and (G) the VH FR4 set forth in SEQ ID NO: 22.

[0453] Exemplary Embodiment 28. The antibody or antigen binding fragment of Exemplary Embodiment 15, wherein (i) the VL comprises (a) the CDRL1 set forth in SEQ ID NO: 7; (c) the CDRL3 set forth in SEQ ID NO: 9; (d) the VL FR1 set forth in SEQ ID NO: 25; (e) the VL FR2 set forth in SEQ ID NO: 28; (f) the VL FR3 set forth in SEQ ID NO: 30; and (g) the VL FR4 set forth in SEQ ID NO: 18; and (ii) the VH comprises (B) the CDRH2 set forth in SEQ ID NO: 11 ; (C) the CDRH3 set forth in SEQ ID NO: 14; (D) the VH FR1 set forth in SEQ ID NO: 33; (E) the VH FR2 set forth in SEQ ID NO: 20; (F) the VH FR3 set forth in SEQ ID NO: 21; and (G) the VH FR4 set forth in SEQ ID NO: 22.

[0454] Exemplary Embodiment 29. The antibody or antigen binding fragment of Exemplary Embodiment 15, wherein (i) the VL comprises (a) the CDRL1 set forth in SEQ ID NO: 7; (c) the CDRL3 set forth in SEQ ID NO: 9; (d) the VL FR1 set forth in SEQ ID NO: 26; (e) the VL FR2 set forth in SEQ ID NO: 28; (f) the VL FR3 set forth in SEQ ID NO: 30; and (g) the VL FR4 set forth in SEQ ID NO: 18; and (ii) the VH comprises (B) the CDRH2 set forth in SEQ ID NO: 11 ; (C) the CDRH3 set forth in SEQ ID NO: 14; (D) the VH FR1 set forth in SEQ ID NO: 33; (E) the VH FR2 set forth in SEQ ID NO: 20; (F) the VH FR3 set forth in SEQ ID NO: 21; and (G) the VH FR4 set forth in SEQ ID NO: 22.

[0455] Exemplary Embodiment 30. The antibody or antigen binding fragment of Exemplary Embodiment 15, wherein (i) the VL comprises (a) the CDRL1 set forth in SEQ ID NO: 7; (c) the130FH13167949.1BPX-05925CDRL3 set forth in SEQ ID NO: 9; (d) the VL FR1 set forth in SEQ ID NO: 27; (e) the VL FR2 set forth in SEQ ID NO: 28; (f) the VL FR3 set forth in SEQ ID NO: 30; and (g) the VL FR4 set forth in SEQ ID NO: 18; and (ii) the VH comprises (B) the CDRH2 set forth in SEQ ID NO: 11 ; (C) the CDRH3 set forth in SEQ ID NO: 14; (D) the VH FR1 set forth in SEQ ID NO: 33; (E) the VH FR2 set forth in SEQ ID NO: 20; (F) the VH FR3 set forth in SEQ ID NO: 21; and (G) the VH FR4 set forth in SEQ ID NO: 22.

[0456] Exemplary Embodiment 31. The antibody or antigen binding fragment of Exemplary Embodiment 15, wherein (i) the VL comprises (a) the CDRL1 set forth in SEQ ID NO: 7; (c) the CDRL3 set forth in SEQ ID NO: 9; (d) the VL FR1 set forth in SEQ ID NO: 23; (e) the VL FR2 set forth in SEQ ID NO: 28; (f) the VL FR3 set forth in SEQ ID NO: 30; and (g) the VL FR4 set forth in SEQ ID NO: 18; and (ii) the VH comprises (B) the CDRH2 set forth in SEQ ID NO: 12; (C) the CDRH3 set forth in SEQ ID NO: 13; (D) the VH FR1 set forth in SEQ ID NO: 33; (E) the VH FR2 set forth in SEQ ID NO: 20; (F) the VH FR3 set forth in SEQ ID NO: 21; and (G) the VH FR4 set forth in SEQ ID NO: 22.

[0457] Exemplary Embodiment 32. The antibody or antigen binding fragment of Exemplary Embodiment 15, wherein (i) the VL comprises (a) the CDRL1 set forth in SEQ ID NO: 7; (c) the CDRL3 set forth in SEQ ID NO: 9; (d) the VL FR1 set forth in SEQ ID NO: 23; (e) the VL FR2 set forth in SEQ ID NO: 28; (f) the VL FR3 set forth in SEQ ID NO: 30; and (g) the VL FR4 set forth in SEQ ID NO: 18; and (ii) the VH comprises (B) the CDRH2 set forth in SEQ ID NO: 12; (C) the CDRH3 set forth in SEQ ID NO: 14; (D) the VH FR1 set forth in SEQ ID NO: 33; (E) the VH FR2 set forth in SEQ ID NO: 20; (F) the VH FR3 set forth in SEQ ID NO: 21; and (G) the VH FR4 set forth in SEQ ID NO: 22.

[0458] Exemplary Embodiment 33. The antibody or antigen binding fragment of Exemplary Embodiment 15, wherein (i) the VL comprises (a) the CDRL1 set forth in SEQ ID NO: 8; (c) the CDRL3 set forth in SEQ ID NO: 9; (d) the VL FR1 set forth in SEQ ID NO: 23; (e) the VL FR2 set forth in SEQ ID NO: 28; (f) the VL FR3 set forth in SEQ ID NO: 30; and (g) the VL FR4 set forth in SEQ ID NO: 18; and (ii) the VH comprises (B) the CDRH2 set forth in SEQ ID NO: 12; (C) the CDRH3 set forth in SEQ ID NO: 14; (D) the VH FR1 set forth in SEQ ID NO: 33; (E) the VH FR2 set forth in SEQ ID NO: 20; (F) the VH FR3 set forth in SEQ ID NO: 21; and (G) the VH FR4 set forth in SEQ ID NO: 22.131FH13167949.1BPX-05925

[0459] Exemplary Embodiment 34. The antibody or antigen binding fragment of Exemplary Embodiment 15, wherein (i) the VL comprises (a) the CDRL1 set forth in SEQ ID NO: 8; (c) the CDRL3 set forth in SEQ ID NO: 9; (d) the VL FR1 set forth in SEQ ID NO: 24; (e) the VL FR2 set forth in SEQ ID NO: 28; (f) the VL FR3 set forth in SEQ ID NO: 30; and (g) the VL FR4 set forth in SEQ ID NO: 18; and (ii) the VH comprises (B) the CDRH2 set forth in SEQ ID NO: 12; (C) the CDRH3 set forth in SEQ ID NO: 14; (D) the VH FR1 set forth in SEQ ID NO: 33; (E) the VH FR2 set forth in SEQ ID NO: 20; (F) the VH FR3 set forth in SEQ ID NO: 21; and (G) the VH FR4 set forth in SEQ ID NO: 22.

[0460] Exemplary Embodiment 35. The antibody or antigen binding fragment of Exemplary Embodiment 15, wherein (i) the VL comprises (a) the CDRL1 set forth in SEQ ID NO: 7; (c) the CDRL3 set forth in SEQ ID NO: 9; (d) the VL FR1 set forth in SEQ ID NO: 24; (e) the VL FR2 set forth in SEQ ID NO: 28; (f) the VL FR3 set forth in SEQ ID NO: 30; and (g) the VL FR4 set forth in SEQ ID NO: 18; and (ii) the VH comprises (B) the CDRH2 set forth in SEQ ID NO: 12; (C) the CDRH3 set forth in SEQ ID NO: 14; (D) the VH FR1 set forth in SEQ ID NO: 33; (E) the VH FR2 set forth in SEQ ID NO: 20; (F) the VH FR3 set forth in SEQ ID NO: 21; and (G) the VH FR4 set forth in SEQ ID NO: 22.

[0461] Exemplary Embodiment 36. The antibody or antigen binding fragment of Exemplary Embodiment 15, wherein (i) the VL comprises (a) the CDRL1 set forth in SEQ ID NO: 8; (c) the CDRL3 set forth in SEQ ID NO: 10; (d) the VL FR1 set forth in SEQ ID NO: 24; (e) the VL FR2 set forth in SEQ ID NO: 28; (f) the VL FR3 set forth in SEQ ID NO: 30; and (g) the VL FR4 set forth in SEQ ID NO: 18; and (ii) the VH comprises (B) the CDRH2 set forth in SEQ ID NO: 12; (C) the CDRH3 set forth in SEQ ID NO: 14; (D) the VH FR1 set forth in SEQ ID NO: 33; (E) the VH FR2 set forth in SEQ ID NO: 20; (F) the VH FR3 set forth in SEQ ID NO: 21; and (G) the VH FR4 set forth in SEQ ID NO: 22.

[0462] Exemplary Embodiment 37. The antibody or antigen binding fragment of Exemplary Embodiment 15, wherein (i) the VL comprises (a) the CDRL1 set forth in SEQ ID NO: 7; (c) the CDRL3 set forth in SEQ ID NO: 10; (d) the VL FR1 set forth in SEQ ID NO: 24; (e) the VL FR2 set forth in SEQ ID NO: 28; (f) the VL FR3 set forth in SEQ ID NO: 30; and (g) the VL FR4 set forth in SEQ ID NO: 18; and (ii) the VH comprises (B) the CDRH2 set forth in SEQ ID NO: 12; (C) the CDRH3 set forth in SEQ ID NO: 14; (D) the VH FR1 set forth in SEQ ID NO: 33; (E) the132FH13167949.1BPX-05925VH FR2 set forth in SEQ ID NO: 20; (F) the VH FR3 set forth in SEQ ID NO: 21; and (G) the VH FR4 set forth in SEQ ID NO: 22.

[0463] Exemplary Embodiment 38. The antibody or antigen binding fragment of Exemplary Embodiment 15, wherein (i) the VL comprises (a) the CDRL1 set forth in SEQ ID NO: 7; (c) the CDRL3 set forth in SEQ ID NO: 9; (d) the VL FR1 set forth in SEQ ID NO: 24; (e) the VL FR2 set forth in SEQ ID NO: 28; (f) the VL FR3 set forth in SEQ ID NO: 30; and (g) the VL FR4 set forth in SEQ ID NO: 18; and (ii) the VH comprises (B) the CDRH2 set forth in SEQ ID NO: 11 ; (C) the CDRH3 set forth in SEQ ID NO: 13; (D) the VH FR1 set forth in SEQ ID NO: 33; (E) the VH FR2 set forth in SEQ ID NO: 20; (F) the VH FR3 set forth in SEQ ID NO: 21; and (G) the VH FR4 set forth in SEQ ID NO: 22.

[0464] Exemplary Embodiment 39. The antibody or antigen binding fragment of Exemplary Embodiment 15, wherein (i) the VL comprises (a) the CDRL1 set forth in SEQ ID NO: 7; (c) the CDRL3 set forth in SEQ ID NO: 9; (d) the VL FR1 set forth in SEQ ID NO: 24; (e) the VL FR2 set forth in SEQ ID NO: 28; (f) the VL FR3 set forth in SEQ ID NO: 30; and (g) the VL FR4 set forth in SEQ ID NO: 18; and (ii) the VH comprises (B) the CDRH2 set forth in SEQ ID NO: 12; (C) the CDRH3 set forth in SEQ ID NO: 13; (D) the VH FR1 set forth in SEQ ID NO: 33; (E) the VH FR2 set forth in SEQ ID NO: 20; (F) the VH FR3 set forth in SEQ ID NO: 21; and (G) the VH FR4 set forth in SEQ ID NO: 22.

[0465] Exemplary Embodiment 40. The antibody or antigen binding fragment of Exemplary Embodiment 15, wherein (i) the VL comprises (a) the CDRL1 set forth in SEQ ID NO: 7; (c) the CDRL3 set forth in SEQ ID NO: 10; (d) the VL FR1 set forth in SEQ ID NO: 24; (e) the VL FR2 set forth in SEQ ID NO: 28; (f) the VL FR3 set forth in SEQ ID NO: 30; and (g) the VL FR4 set forth in SEQ ID NO: 18; and (ii) the VH comprises (B) the CDRH2 set forth in SEQ ID NO: 12; (C) the CDRH3 set forth in SEQ ID NO: 13; (D) the VH FR1 set forth in SEQ ID NO: 33; (E) the VH FR2 set forth in SEQ ID NO: 20; (F) the VH FR3 set forth in SEQ ID NO: 21; and (G) the VH FR4 set forth in SEQ ID NO: 22.

[0466] Exemplary Embodiment 41. The antibody or antigen binding fragment of Exemplary Embodiment 15, wherein the VH and the VL comprise amino acid sequences having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequences selected from (a) SEQ ID NOs: 35 and 40, respectively; (b) SEQ ID NOs: 35 and 49, respectively; (c) SEQ ID NOs: 35 and 50, respectively; (d) SEQ ID NOs: 35 and 41, respectively; (e) SEQ ID NOs: 35133FH13167949.1BPX-05925 and 46, respectively; (f) SEQ ID NOs: 36 and 50, respectively; (g) SEQ ID NOs: 36 and 40, respectively; (h) SEQ ID NOs: 36 and 41, respectively; (i) SEQ ID NOs: 36 and 42, respectively; (j) SEQ ID NOs: 36 and 43, respectively; (k) SEQ ID NOs: 36 and 44, respectively; (1) SEQ ID NOs: 37 and 50, respectively; (m) SEQ ID NOs: 37 and 40, respectively; (n) SEQ ID NOs: 37 and 46, respectively; (o) SEQ ID NOs: 37 and 48, respectively; (p) SEQ ID NOs: 38 and 50, respectively; (q) SEQ ID NOs: 38 and 51, respectively; (r) SEQ ID NOs: 38 and 52, respectively; (s) SEQ ID NOs: 38 and 40, respectively; (t) SEQ ID NOs: 38 and 41, respectively; (u) SEQ ID NOs: 38 and 45, respectively; (v) SEQ ID NOs: 38 and 46, respectively; (w) SEQ ID NOs: 38 and 47, respectively; (x) SEQ ID NOs: 38 and 48, respectively; and (y) SEQ ID NOs: 39 and 40, respectively.

[0467] Exemplary Embodiment 42. The antibody or antigen binding fragment of claim 15, wherein the VH and the VL comprise the amino acid sequences selected from (a) SEQ ID NOs: 35 and 40, respectively; (b) SEQ ID NOs: 35 and 49, respectively; (c) SEQ ID NOs: 35 and 50, respectively; (d) SEQ ID NOs: 35 and 41, respectively; (e) SEQ ID NOs: 35 and 46, respectively;(f) SEQ ID NOs: 36 and 50, respectively; (g) SEQ ID NOs: 36 and 40, respectively; (h) SEQ ID NOs: 36 and 41, respectively; (i) SEQ ID NOs: 36 and 42, respectively; (j) SEQ ID NOs: 36 and 43, respectively; (k) SEQ ID NOs: 36 and 44, respectively; (1) SEQ ID NOs: 37 and 50, respectively; (m) SEQ ID NOs: 37 and 40, respectively; (n) SEQ ID NOs: 37 and 46, respectively; (o) SEQ ID NOs: 37 and 48, respectively; (p) SEQ ID NOs: 38 and 50, respectively; (q) SEQ ID NOs: 38 and 51, respectively; (r) SEQ ID NOs: 38 and 52, respectively; (s) SEQ ID NOs: 38 and 40, respectively; (t) SEQ ID NOs: 38 and 41, respectively; (u) SEQ ID NOs: 38 and 45, respectively; (v) SEQ ID NOs: 38 and 46, respectively; (w) SEQ ID NOs: 38 and 47, respectively; (x) SEQ ID NOs: 38 and 48, respectively; and (y) SEQ ID NOs: 39 and 40, respectively.

[0468] Exemplary Embodiment 43. The antibody or antigen binding fragment of any one of Exemplary Embodiments 1-42, comprising a heavy chain constant region.

[0469] Exemplary Embodiment 44. The antibody or antigen binding fragment of Exemplary Embodiment 43, wherein the heavy chain constant region is an IgG constant region.

[0470] Exemplary Embodiment 45. The antibody or antigen binding fragment of Exemplary Embodiment 44, wherein the IgG constant region is a wild-type IgG constant region.134FH13167949.1BPX-05925

[0471] Exemplary Embodiment 46. The antibody or antigen binding fragment of Exemplary Embodiment 44, wherein the IgG constant region comprises at least one mutation relative to a wildtype IgG constant region.

[0472] Exemplary Embodiment 47. The antibody or antigen binding fragment of any one of Exemplary Embodiments 44-46, wherein the IgG constant region is an IgGl, IgG2, IgG3, or IgG4 constant region.

[0473] Exemplary Embodiment 48. The antibody or antigen binding fragment of Exemplary Embodiment 47, wherein the IgG constant region is an IgGl constant region.

[0474] Exemplary Embodiment 49. The antibody or antigen binding fragment of Exemplary Embodiment 47, wherein the IgGl constant region is a wild-type human IgGl constant region.

[0475] Exemplary Embodiment 50. The antibody or antigen binding fragment of Exemplary Embodiment 47, wherein the IgGl constant region comprises at least one amino acid substitution relative to a wild-t...

Claims

BPX-05925CLAIMS1. An antibody, or antigen binding fragment thereof, that specifically binds complement component 2 (C2), wherein the antibody or antigen binding fragment comprises a light chain variable region (VL) and a heavy chain variable region (VH), wherein: the VL comprises a VL complementarity determining region (CDR) 1 (CDRL1) set forth in SEQ ID NO: 184 (XITX2TDIDDDMN), a VL CDR 2 (CDRL2) set forth in SEQ ID NO: 2 (EGNTLRP), and a VL CDR 3 (CDRL3) set forth in SEQ ID NO: 185 (X3QSDX4LPFT); and the VH comprises a VH CDR 1 (CDRH1) set forth in SEQ ID NO: 4 (GYTFTDYNMH), a VH CDR 2 (CDRH2) set forth in SEQ ID NO: 5 (YVYPX5IGGTG), and a VH CDR 3 (CDRH3) set forth in SEQ ID NO: 186 (RGX6X7GIFDY), wherein Xi is I or R; X2is F or H; X3 is L or Q; X4 is N or H; X5 is Y or S; Xs is Y or H; X7 is D or E, and wherein at least one of X3 is Q, X5 is S, and X7 is E.

2. The antibody or antigen binding fragment of claim 1, wherein:(1) the CDRL1 is set forth in SEQ ID NO: 8 (RTFTDIDDDMN), the CDRL3 is set forth in SEQ ID NO: 190 (QQSDHLPFT), the CDRH2 is set forth in SEQ ID NO: 12 (YVYPSIGGTG), and the CDRH3 is set forth in SEQ ID NO: 14 (RGYEGIFDY);(ii) the CDRL1 is set forth in SEQ ID NO: 188 (RTHTDIDDDMN), the CDRL3 is set forth in SEQ ID NO: 190, the CDRH2 is set forth in SEQ ID NO: 12, and the CDRH3 is set forth in SEQ ID NO: 14;(hi) the CDRL1 is set forth in SEQ ID NO: 8, the CDRL3 is set forth in SEQ ID NO: 190, the CDRH2 is set forth in SEQ ID NO: 12, and the CDRH3 is set forth in SEQ ID NO: 191 (RGHEGIFDY);(iv) the CDRL1 is set forth in SEQ ID NO: 8, the CDRL3 is set forth in SEQ ID NO: 189 (LQSDHLPFT), the CDRH2 is set forth in SEQ ID NO: 12, and the CDRH3 is set forth in SEQ ID NO: 14;(v) the CDRL1 is set forth in SEQ ID NO: 8, the CDRL3 is set forth in SEQ ID NO: 9 (LQSDNLPFT), the CDRH2 is set forth in SEQ ID NO: 12, and the CDRH3 is set forth in SEQ ID NO: 14;(vi) the CDRL1 is set forth in SEQ ID NO: 8, the CDRL3 is set forth in SEQ ID NO: 9, the CDRH2 is set forth in SEQ ID NO: 12, and the CDRH3 is set forth in SEQ ID NO: 191;186FH13167949.1BPX-05925(vn) the CDRL1 is set forth in SEQ ID NO: 8, the CDRL3 is set forth in SEQ ID NO: 189, the CDRH2 is set forth in SEQ ID NO: 12, and the CDRH3 is set forth in SEQ ID NO: 191; or(viii) the CDRL1 is set forth in SEQ ID NO: 188, the CDRL3 is set forth in SEQ ID NO: 189, the CDRH2 is set forth in SEQ ID NO: 12, and the CDRH3 is set forth in SEQ ID NO: 14.

3. The antibody or antigen binding fragment of claim 1, wherein: the CDRL1 is set forth in SEQ ID NO: 1 (XsTFTDIDDDMN), the CDRL3 is set forth in SEQ ID NO: 3 (X9QSDNLPFT), the CDRH2 is set forth in SEQ ID NO: 5 (YVYPX5IGGTG), and the CDRH3 is set forth in SEQ ID NO: 6 (RGYX10GIFDY), wherein X8is I or R; X9is L or Q; X5is Y or S; and X10 is D or E, and wherein at least one of X9is Q, X5 is S, and X10 is E.

4. The antibody or antigen binding fragment of claim 3, wherein:(1) the CDRL1 is set forth in SEQ ID NO: 8, the CDRL3 is set forth in SEQ ID NO: 9, the CDRH2 is set forth in SEQ ID NO: 11 (YVYPYIGGTG), and the CDRH3 is set forth in SEQ ID NO: 14;(ii) the CDRL1 is set forth in SEQ ID NO: 8, the CDRL3 is set forth in SEQ ID NO: 9, the CDRH2 is set forth in SEQ ID NO: 12, and the CDRH3 is set forth in SEQ ID NO: 13 (RGYDGIFDY);(iii) the CDRL1 is set forth in SEQ ID NO: 8, the CDRL3 is set forth in SEQ ID NO: 9, the CDRH2 is set forth in SEQ ID NO: 12, and the CDRH3 is set forth in SEQ ID NO: 14;(iv) the CDRL1 is set forth in SEQ ID NO: 8, the CDRL3 is set forth in SEQ ID NO: 10 (QQSDNLPFT), the CDRH2 is set forth in SEQ ID NO: 12, and the CDRH3 is set forth in SEQ ID NO: 14;(v) the CDRL1 is set forth in SEQ ID NO: 7 (ITFTDIDDDMN), the CDRL3 is set forth in SEQ ID NO: 9, the CDRH2 is set forth in SEQ ID NO: 12, and the CDRH3 is set forth in SEQ ID NO: 14;(vi) the CDRL1 is set forth in SEQ ID NO: 7, the CDRL3 is set forth in SEQ ID NO: 9, the CDRH2 is set forth in SEQ ID NO: 11, and the CDRH3 is set forth in SEQ ID NO: 14;(vii) the CDRL1 is set forth in SEQ ID NO: 7, the CDRL3 is set forth in SEQ ID NO: 9, the CDRH2 is set forth in SEQ ID NO: 12, and the CDRH3 is set forth in SEQ ID NO: 13;(viii) the CDRL1 is set forth in SEQ ID NO: 7, the CDRL3 is set forth in SEQ ID NO: 10, the CDRH2 is set forth in SEQ ID NO: 12, and the CDRH3 is set forth in SEQ ID NO: 14; or187FH13167949.1BPX-05925(ix) the CDRL1 is set forth in SEQ ID NO: 7, the CDRL3 is set forth in SEQ ID NO: 10, the CDRH2 is set forth in SEQ ID NO: 12, and the CDRH3 is set forth in SEQ ID NO: 13.

5. The antibody or antigen binding fragment of any one of claims 1-4, wherein the VL comprises at least one VL framework region (FR) selected from SEQ ID NOs: 15 (ETTVTQSPSSLSX11SVGX12RVTIX13C), 16 (WYQQKPGKX14PKLLIS), 17 (GVPSRFSX18SGYGTDFTFTISSMQPEDX19ATYYC), 18 (FGQGTKLEIK), and 187 (GVPSRFSX15SGX16GTDFTFTISSMQPEDX17ATYYC), wherein Xu is M or A; X12 is D or E; X13 is T or R; X14 is P or A; X15 is S or G; Xi6 is Y or H; X17 is V or F; Xis is S or G; and X19 is V or F.

6. The antibody or antigen binding fragment of any one of claims 1-5, wherein the VL comprises a FR1 region selected from SEQ ID NOs: 23, 24, 25, 26, and 27, a FR2 region selected from SEQ ID NOs: 28 and 29, a FR3 region selected from SEQ ID NOs: 30, 31, 32, 192, and 193, and a FR4 region set forth in SEQ ID NO: 18.

7. The antibody or antigen binding fragment of any one of claims 1-6, wherein the VL comprises a FR1 region set forth in SEQ ID NO: 23, a FR2 region set forth in SEQ ID NO: 28, a FR3 region set forth in SEQ ID NO: 30, and a FR4 region set forth in SEQ ID NO: 18.

8. The antibody or antigen binding fragment of any one of claims 1-6, wherein the VL comprises a FR1 region set forth in SEQ ID NO: 23, a FR2 region set forth in SEQ ID NO: 28, a FR3 region set forth in SEQ ID NO: 192, and a FR4 region set forth in SEQ ID NO: 18.

9. The antibody or antigen binding fragment of any one of claims 1-6, wherein the VL comprises a FR1 region set forth in SEQ ID NO: 24, a FR2 region set forth in SEQ ID NO: 28, a FR3 region set forth in SEQ ID NO: 30, and a FR4 region set forth in SEQ ID NO: 18.

10. The antibody or antigen binding fragment of any one of claims 1-6, wherein the VL comprises a FR1 region set forth in SEQ ID NO: 24, a FR2 region set forth in SEQ ID NO: 28, a FR3 region set forth in SEQ ID NO: 192, and a FR4 region set forth in SEQ ID NO: 18.188FH13167949.1BPX-0592511. The antibody or antigen binding fragment of any one of claims 1-6, wherein the VL comprises a FR1 region set forth in SEQ ID NO: 24, a FR2 region set forth in SEQ ID NO: 29, a FR3 region set forth in SEQ ID NO: 31, and a FR4 region set forth in SEQ ID NO: 18.

12. The antibody or antigen binding fragment of any one of claims 1-6, wherein the VL comprises a FR1 region set forth in SEQ ID NO: 24, a FR2 region set forth in SEQ ID NO: 29, a FR3 region set forth in SEQ ID NO: 32, and a FR4 region set forth in SEQ ID NO: 18.

13. The antibody or antigen binding fragment of any one of claims 1-6, wherein the VL comprises a FR1 region set forth in SEQ ID NO: 24, a FR2 region set forth in SEQ ID NO: 29, a FR3 region set forth in SEQ ID NO: 193, and a FR4 region set forth in SEQ ID NO: 18.

14. The antibody or antigen binding fragment of any one of claims 1-13, wherein the VH comprises at least one VH FR selected from SEQ ID NOs: 19-22.

15. The antibody or antigen binding fragment of any one of claims 1-14, wherein the VH comprises a FR1 region selected from SEQ ID NOs: 33 and 34, a FR2 region set forth in SEQ ID NO: 20, a FR3 region set forth in SEQ ID NO: 21, and a FR4 region set forth in SEQ ID NO: 22.

16. The antibody or antigen binding fragment of any one of claims 1-11 and 14-15, wherein the VH comprises a FR1 region set forth in SEQ ID NO: 33, a FR2 region set forth in SEQ ID NO: 20, a FR3 region set forth in SEQ ID NO: 21, and a FR4 region set forth in SEQ ID NO: 22.

17. The antibody or antigen binding fragment of any one of claims 1-15, wherein the VH comprises a FR1 region set forth in SEQ ID NO: 33, a FR2 region set forth in SEQ ID NO: 20, a FR3 region set forth in SEQ ID NO: 21, and a FR4 region set forth in SEQ ID NO: 22.

18. The antibody or antigen binding fragment of any one of claims 1-6 and 14-15, wherein the VH comprises a FR1 region set forth in SEQ ID NO: 34, a FR2 region set forth in SEQ ID NO: 20, a FR3 region set forth in SEQ ID NO: 21, and a FR4 region set forth in SEQ ID NO: 22.189FH13167949.1BPX-0592519. The antibody or antigen binding fragment of any one of claims 1-18, wherein the VH and the VL comprise amino acid sequences having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequences selected from:(a) SEQ ID NOs: 36 and 50, respectively;(b) SEQ ID NOs: 37 and 50, respectively;(c) SEQ ID NOs: 38 and 50, respectively;(d) SEQ ID NOs: 38 and 51, respectively;(e) SEQ ID NOs: 38 and 52, respectively;(f) SEQ ID NOs: 36 and 40, respectively;(g) SEQ ID NOs: 36 and 41, respectively;(h) SEQ ID NOs: 36 and 42, respectively;(i) SEQ ID NOs: 36 and 43, respectively;(j) SEQ ID NOs: 36 and 44, respectively;(k) SEQ ID NOs: 37 and 40, respectively;(l) SEQ ID NOs: 38 and 40, respectively;(m) SEQ ID NOs: 38 and 41, respectively;(n) SEQ ID NOs: 38 and 45, respectively;(o) SEQ ID NOs: 38 and 46, respectively;(p) SEQ ID NOs: 38 and 47, respectively;(q) SEQ ID NOs: 38 and 48, respectively;(r) SEQ ID NOs: 37 and 46, respectively;(s) SEQ ID NOs: 37 and 48, respectively;(t) SEQ ID NOs: 38 and 195, respectively;(u) SEQ ID NOs: 38 and 196, respectively;(v) SEQ ID NOs: 38 and 197, respectively;(w) SEQ ID NOs: 194 and 41, respectively;(x) SEQ ID NOs: 194 and 195, respectively;(y) SEQ ID NOs: 38 and 198, respectively;(z) SEQ ID NOs: 38 and 199, respectively;(aa) SEQ ID NOs: 194 and 197, respectively;(bb) SEQ ID NOs: 38 and 200, respectively;(cc) SEQ ID NOs: 38 and 201, respectively;190FH13167949.1BPX-05925(dd) SEQ ID NOs: 194 and 200, respectively;(ee) SEQ ID NOs: 38 and 202, respectively;(ff) SEQ ID NOs: 38 and 203, respectively; and(gg) SEQ ID NOs: 194 and 202, respectively.

20. The antibody or antigen binding fragment of any one of claims 1-18, wherein the VH and the VL comprise the amino acid sequences selected from:(a) SEQ ID NOs: 36 and 50, respectively;(b) SEQ ID NOs: 37 and 50, respectively;(c) SEQ ID NOs: 38 and 50, respectively;(d) SEQ ID NOs: 38 and 51, respectively;(e) SEQ ID NOs: 38 and 52, respectively;(f) SEQ ID NOs: 36 and 40, respectively;(g) SEQ ID NOs: 36 and 41, respectively;(h) SEQ ID NOs: 36 and 42, respectively;(i) SEQ ID NOs: 36 and 43, respectively;(j) SEQ ID NOs: 36 and 44, respectively;(k) SEQ ID NOs: 37 and 40, respectively;(l) SEQ ID NOs: 38 and 40, respectively;(m) SEQ ID NOs: 38 and 41, respectively;(n) SEQ ID NOs: 38 and 45, respectively;(o) SEQ ID NOs: 38 and 46, respectively;(p) SEQ ID NOs: 38 and 47, respectively;(q) SEQ ID NOs: 38 and 48, respectively;(r) SEQ ID NOs: 37 and 46, respectively;(s) SEQ ID NOs: 37 and 48, respectively;(t) SEQ ID NOs: 38 and 195, respectively;(u) SEQ ID NOs: 38 and 196, respectively;(v) SEQ ID NOs: 38 and 197, respectively;(w) SEQ ID NOs: 194 and 41, respectively;(x) SEQ ID NOs: 194 and 195, respectively;(y) SEQ ID NOs: 38 and 198, respectively;191FH13167949.1BPX-05925(z) SEQ ID NOs: 38 and 199, respectively;(aa) SEQ ID NOs: 194 and 197, respectively;(bb) SEQ ID NOs: 38 and 200, respectively;(cc) SEQ ID NOs: 38 and 201, respectively;(dd) SEQ ID NOs: 194 and 200, respectively;(ee) SEQ ID NOs: 38 and 202, respectively;(ff) SEQ ID NOs: 38 and 203, respectively; and(gg) SEQ ID NOs: 194 and 202, respectively.

21. An antibody, or antigen binding fragment thereof, that specifically binds complement component 2 (C2), wherein the antibody or antigen binding fragment comprises:(i) a VL comprising:(a) a CDRL1 set forth in SEQ ID NO: 184 (XITX2TDIDDDMN), wherein Xi is I or R; X2is F or H;(b) a CDRL2 set forth in SEQ ID NO: 2 (EGNTLRP);(c) a CDRL3 set forth in SEQ ID NO: 185 (X3QSDX4LPFT), wherein X3is L or Q; X4is N or H;(d) a VL FR1 comprising an amino acid sequence having at least 95% identity to SEQ ID NO: 15 (ETTVTQSPSSLSXHSVGXI2RVTIXI3C), wherein Xu is M or A; Xi2is D or E; Xi3is T or R;(e) a VL FR2 comprising an amino acid sequence having at least 95% identity to SEQ ID NO: 16 (WYQQKPGKX14PKLLIS), wherein Xi4is P or A;(f) a VL FR3 comprising an amino acid sequence having at least 95% identity to SEQ ID NO: 187 (GVPSRFSX15SGX16GTDFTFTISSMQPEDX17ATYYC), wherein Xi5is S or G; Xi6is Y or H; X17 is V or F;(g) a VL FR4 comprising an amino acid sequence having at least 95% identity to SEQ ID NO: 18 (FGQGTKLEIK); and(ii) a VH comprising:(A) a CDRH1 set forth in SEQ ID NO: 4 (GYTFTDYNMH);(B) a CDRH2 set forth in SEQ ID NO: 5 (YVYPX5IGGTG), wherein X5is Y or S;(C) a CDRH3 set forth in SEQ ID NO: 186 (RGX6X7GIFDY), wherein Xg is Y or H; X7 is D or E;192FH13167949.1BPX-05925(D) a VH FR1 comprising an amino acid sequence having at least 95% identity to SEQ ID NO: 19 (X20VQLVQSGAEVKKPGASVKISCKAS), wherein X20 is E or Q;(E) a VH FR2 comprising an amino acid sequence having at least 95% identity to SEQ ID NO: 20 (WVRQAPGQGLEWIG);(F) a VH FR3 comprising an amino acid sequence having at least 95% identity to SEQ ID NO: 21 (YNQKFKNRATLTVDTSTSTAYMELSSLRSEDTAVYYCTR); and(G) a VH FR4 comprising an amino acid sequence having at least 95% identity to SEQ ID NO: 22 (WGQGTTLTVSS).

22. The antibody or antigen binding fragment of claim 21, wherein:(i) the VL comprises:(a) the CDRL1 set forth in SEQ ID NO: 1 (X8TFTDIDDDMN), wherein X8is I or R;(c) the CDRL3 set forth in SEQ ID NO: 3 (X9QSDNLPFT), wherein X9is L or Q; and(f) the VL FR3 comprising an amino acid sequence having at least 95% identity to SEQ ID NO: 17 (GVPSRFSXI8SGYGTDFTFTISSMQPEDXI9ATYYC), wherein Xi8is S or G; Xi9is V or F; and(ii) the VH comprises:(C) the CDRH3 set forth in SEQ ID NO: 6 (RGYX10GIFDY), wherein X10 is D or E.

23. The antibody or antigen binding fragment of claim 21, wherein:(i) the VL comprises:(a) the CDRL1 set forth in SEQ ID NO: 7;(c) the CDRL3 set forth in SEQ ID NO: 9;(d) the VL FR1 set forth in SEQ ID NO: 23 (ETTVTQSPSSLSMSVGDRVTITC);(e) the VL FR2 set forth in SEQ ID NO: 28 (WYQQKPGKPPKLLIS);(f) the VL FR3 set forth in SEQ ID NO: 30(GVPSRF S S SGYGTDFTFTIS SMQPED VATYYC) ; and(g) the VL FR4 set forth in SEQ ID NO: 18; and(ii) the VH comprises:(B) the CDRH2 set forth in SEQ ID NO: 11 ;(C) the CDRH3 set forth in SEQ ID NO: 13;193FH13167949.1BPX-05925(D) the VH FR1 set forth in SEQ ID NO: 33 (EVQLVQSGAEVKKPGASVKISCKAS);(E) the VH FR2 set forth in SEQ ID NO: 20;(F) the VH FR3 set forth in SEQ ID NO: 21 ; and(G) the VH FR4 set forth in SEQ ID NO: 22.

24. The antibody or antigen binding fragment of claim 21, wherein:(i) the VL comprises:(a) the CDRL1 set forth in SEQ ID NO: 7;(c) the CDRL3 set forth in SEQ ID NO: 9;(d) the VL FR1 set forth in SEQ ID NO: 23;(e) the VL FR2 set forth in SEQ ID NO: 28;(f) the VL FR3 set forth in SEQ ID NO: 30; and(g) the VL FR4 set forth in SEQ ID NO: 18; and(ii) the VH comprises:(B) the CDRH2 set forth in SEQ ID NO: 11 ;(C) the CDRH3 set forth in SEQ ID NO: 13;(D) the VH FR1 set forth in SEQ ID NO: 34 (QVQLVQSGAEVKKPGASVKISCKAS);(E) the VH FR2 set forth in SEQ ID NO: 20;(F) the VH FR3 set forth in SEQ ID NO: 21 ; and(G) the VH FR4 set forth in SEQ ID NO: 22.

25. The antibody or antigen binding fragment of claim 21, wherein:(i) the VL comprises:(a) the CDRL1 set forth in SEQ ID NO: 7;(c) the CDRL3 set forth in SEQ ID NO: 9;(d) the VL FR1 set forth in SEQ ID NO: 24 (ETTVTQSPSSLSASVGDRVTITC);(e) the VL FR2 set forth in SEQ ID NO: 29 (WYQQKPGKAPKLLIS);(f) the VL FR3 set forth in SEQ ID NO: 31 (GVPSRFSSSGYGTDFTFTISSMQPEDFATYYC); and(g) the VL FR4 set forth in SEQ ID NO: 18; and194FH13167949.1BPX-05925(ii) the VH comprises:(B) the CDRH2 set forth in SEQ ID NO: 11 ;(C) the CDRH3 set forth in SEQ ID NO: 13;(D) the VH FR1 set forth in SEQ ID NO: 33;(E) the VH FR2 set forth in SEQ ID NO: 20;(F) the VH FR3 set forth in SEQ ID NO: 21 ; and(G) the VH FR4 set forth in SEQ ID NO: 22.

26. The antibody or antigen binding fragment of claim 21, wherein:(i) the VL comprises:(a) the CDRL1 set forth in SEQ ID NO: 8;(c) the CDRL3 set forth in SEQ ID NO: 9;(d) the VL FR1 set forth in SEQ ID NO: 24;(e) the VL FR2 set forth in SEQ ID NO: 29;(f) the VL FR3 set forth in SEQ ID NO: 32(GVPSRFSGSGYGTDFTFTISSMQPEDFATYYC); and(g) the VL FR4 set forth in SEQ ID NO: 18; and(ii) the VH comprises:(B) the CDRH2 set forth in SEQ ID NO: 11 ;(C) the CDRH3 set forth in SEQ ID NO: 13;(D) the VH FR1 set forth in SEQ ID NO: 33;(E) the VH FR2 set forth in SEQ ID NO: 20;(F) the VH FR3 set forth in SEQ ID NO: 21 ; and(G) the VH FR4 set forth in SEQ ID NO: 22.

27. The antibody or antigen binding fragment of claim 21, wherein:(i) the VL comprises:(a) the CDRL1 set forth in SEQ ID NO: 8;(c) the CDRL3 set forth in SEQ ID NO: 9;(d) the VL FR1 set forth in SEQ ID NO: 23;(e) the VL FR2 set forth in SEQ ID NO: 28;(f) the VL FR3 set forth in SEQ ID NO: 30; and195FH13167949.1BPX-05925(g) the VL FR4 set forth in SEQ ID NO: 18; and(ii) the VH comprises:(B) the CDRH2 set forth in SEQ ID NO: 11 ;(C) the CDRH3 set forth in SEQ ID NO: 13;(D) the VH FR1 set forth in SEQ ID NO: 33;(E) the VH FR2 set forth in SEQ ID NO: 20;(F) the VH FR3 set forth in SEQ ID NO: 21 ; and(G) the VH FR4 set forth in SEQ ID NO: 22.

28. The antibody or antigen binding fragment of claim 21, wherein:(i) the VL comprises:(a) the CDRL1 set forth in SEQ ID NO: 8;(c) the CDRL3 set forth in SEQ ID NO: 9;(d) the VL FR1 set forth in SEQ ID NO: 24;(e) the VL FR2 set forth in SEQ ID NO: 29;(f) the VL FR3 set forth in SEQ ID NO: 32; and(g) the VL FR4 set forth in SEQ ID NO: 18; and(ii) the VH comprises:(B) the CDRH2 set forth in SEQ ID NO: 11 ;(C) the CDRH3 set forth in SEQ ID NO: 14;(D) the VH FR1 set forth in SEQ ID NO: 33;(E) the VH FR2 set forth in SEQ ID NO: 20;(F) the VH FR3 set forth in SEQ ID NO: 21 ; and(G) the VH FR4 set forth in SEQ ID NO: 22.

29. The antibody or antigen binding fragment of claim 21, wherein:(i) the VL comprises:(a) the CDRL1 set forth in SEQ ID NO: 8;(c) the CDRL3 set forth in SEQ ID NO: 9;(d) the VL FR1 set forth in SEQ ID NO: 24;(e) the VL FR2 set forth in SEQ ID NO: 29;(f) the VL FR3 set forth in SEQ ID NO: 32; and196FH13167949.1BPX-05925(g) the VL FR4 set forth in SEQ ID NO: 18; and(ii) the VH comprises:(B) the CDRH2 set forth in SEQ ID NO: 12;(C) the CDRH3 set forth in SEQ ID NO: 13;(D) the VH FR1 set forth in SEQ ID NO: 33;(E) the VH FR2 set forth in SEQ ID NO: 20;(F) the VH FR3 set forth in SEQ ID NO: 21 ; and(G) the VH FR4 set forth in SEQ ID NO: 22.

30. The antibody or antigen binding fragment of claim 21, wherein:(i) the VL comprises:(a) the CDRL1 set forth in SEQ ID NO: 8;(c) the CDRL3 set forth in SEQ ID NO: 9;(d) the VL FR1 set forth in SEQ ID NO: 24;(e) the VL FR2 set forth in SEQ ID NO: 29;(f) the VL FR3 set forth in SEQ ID NO: 32; and(g) the VL FR4 set forth in SEQ ID NO: 18; and(ii) the VH comprises:(B) the CDRH2 set forth in SEQ ID NO: 12;(C) the CDRH3 set forth in SEQ ID NO: 14;(D) the VH FR1 set forth in SEQ ID NO: 33;(E) the VH FR2 set forth in SEQ ID NO: 20;(F) the VH FR3 set forth in SEQ ID NO: 21 ; and(G) the VH FR4 set forth in SEQ ID NO: 22.

31. The antibody or antigen binding fragment of claim 21 , wherein:(i) the VL comprises:(a) the CDRL1 set forth in SEQ ID NO: 8;(c) the CDRL3 set forth in SEQ ID NO: 10;(d) the VL FR1 set forth in SEQ ID NO: 24;(e) the VL FR2 set forth in SEQ ID NO: 29;(f) the VL FR3 set forth in SEQ ID NO: 32; and197FH13167949.1BPX-05925(g) the VL FR4 set forth in SEQ ID NO: 18; and(ii) the VH comprises:(B) the CDRH2 set forth in SEQ ID NO: 12;(C) the CDRH3 set forth in SEQ ID NO: 14;(D) the VH FR1 set forth in SEQ ID NO: 33;(E) the VH FR2 set forth in SEQ ID NO: 20;(F) the VH FR3 set forth in SEQ ID NO: 21 ; and(G) the VH FR4 set forth in SEQ ID NO: 22.

32. The antibody or antigen binding fragment of claim 21, wherein:(i) the VL comprises:(a) the CDRL1 set forth in SEQ ID NO: 7;(c) the CDRL3 set forth in SEQ ID NO: 9;(d) the VL FR1 set forth in SEQ ID NO: 24;(e) the VL FR2 set forth in SEQ ID NO: 29;(f) the VL FR3 set forth in SEQ ID NO: 32; and(g) the VL FR4 set forth in SEQ ID NO: 18; and(ii) the VH comprises:(B) the CDRH2 set forth in SEQ ID NO: 12;(C) the CDRH3 set forth in SEQ ID NO: 14;(D) the VH FR1 set forth in SEQ ID NO: 33;(E) the VH FR2 set forth in SEQ ID NO: 20;(F) the VH FR3 set forth in SEQ ID NO: 21 ; and(G) the VH FR4 set forth in SEQ ID NO: 22.

33. The antibody or antigen binding fragment of claim 21, wherein:(i) the VL comprises:(a) the CDRL1 set forth in SEQ ID NO: 7;(c) the CDRL3 set forth in SEQ ID NO: 9;(d) the VL FR1 set forth in SEQ ID NO: 23;(e) the VL FR2 set forth in SEQ ID NO: 28;(f) the VL FR3 set forth in SEQ ID NO: 30; and198FH13167949.1BPX-05925(g) the VL FR4 set forth in SEQ ID NO: 18; and(ii) the VH comprises:(B) the CDRH2 set forth in SEQ ID NO: 11 ;(C) the CDRH3 set forth in SEQ ID NO: 14;(D) the VH FR1 set forth in SEQ ID NO: 33;(E) the VH FR2 set forth in SEQ ID NO: 20;(F) the VH FR3 set forth in SEQ ID NO: 21 ; and(G) the VH FR4 set forth in SEQ ID NO: 22.

34. The antibody or antigen binding fragment of claim 21, wherein:(i) the VL comprises:(a) the CDRL1 set forth in SEQ ID NO: 8;(c) the CDRL3 set forth in SEQ ID NO: 9;(d) the VL FR1 set forth in SEQ ID NO: 23;(e) the VL FR2 set forth in SEQ ID NO: 28;(f) the VL FR3 set forth in SEQ ID NO: 30; and(g) the VL FR4 set forth in SEQ ID NO: 18; and(ii) the VH comprises:(B) the CDRH2 set forth in SEQ ID NO: 11 ;(C) the CDRH3 set forth in SEQ ID NO: 14;(D) the VH FR1 set forth in SEQ ID NO: 33;(E) the VH FR2 set forth in SEQ ID NO: 20;(F) the VH FR3 set forth in SEQ ID NO: 21 ; and(G) the VH FR4 set forth in SEQ ID NO: 22.

35. The antibody or antigen binding fragment of claim 21, wherein:(i) the VL comprises:(a) the CDRL1 set forth in SEQ ID NO: 7;(c) the CDRL3 set forth in SEQ ID NO: 9;(d) the VL FR1 set forth in SEQ ID NO: 25 (ETTVTQSPSSLSMSVGDRVTIRC);(e) the VL FR2 set forth in SEQ ID NO: 28;(f) the VL FR3 set forth in SEQ ID NO: 30; and199FH13167949.1BPX-05925(g) the VL FR4 set forth in SEQ ID NO: 18; and(ii) the VH comprises:(B) the CDRH2 set forth in SEQ ID NO: 11 ;(C) the CDRH3 set forth in SEQ ID NO: 14;(D) the VH FR1 set forth in SEQ ID NO: 33;(E) the VH FR2 set forth in SEQ ID NO: 20;(F) the VH FR3 set forth in SEQ ID NO: 21 ; and(G) the VH FR4 set forth in SEQ ID NO: 22.

36. The antibody or antigen binding fragment of claim 21, wherein:(i) the VL comprises:(a) the CDRL1 set forth in SEQ ID NO: 7;(c) the CDRL3 set forth in SEQ ID NO: 9;(d) the VL FR1 set forth in SEQ ID NO: 26 (ETTVTQSPSSLSMSVGERVTITC);(e) the VL FR2 set forth in SEQ ID NO: 28;(f) the VL FR3 set forth in SEQ ID NO: 30; and(g) the VL FR4 set forth in SEQ ID NO: 18; and(ii) the VH comprises:(B) the CDRH2 set forth in SEQ ID NO: 11 ;(C) the CDRH3 set forth in SEQ ID NO: 14;(D) the VH FR1 set forth in SEQ ID NO: 33;(E) the VH FR2 set forth in SEQ ID NO: 20;(F) the VH FR3 set forth in SEQ ID NO: 21 ; and(G) the VH FR4 set forth in SEQ ID NO: 22.

37. The antibody or antigen binding fragment of claim 21, wherein:(i) the VL comprises:(a) the CDRL1 set forth in SEQ ID NO: 7;(c) the CDRL3 set forth in SEQ ID NO: 9;(d) the VL FR1 set forth in SEQ ID NO: 27 (ETTVTQSPSSLSMSVGERVTIRC);(e) the VL FR2 set forth in SEQ ID NO: 28;(f) the VL FR3 set forth in SEQ ID NO: 30; and200FH13167949.1BPX-05925(g) the VL FR4 set forth in SEQ ID NO: 18; and(ii) the VH comprises:(B) the CDRH2 set forth in SEQ ID NO: 11 ;(C) the CDRH3 set forth in SEQ ID NO: 14;(D) the VH FR1 set forth in SEQ ID NO: 33;(E) the VH FR2 set forth in SEQ ID NO: 20;(F) the VH FR3 set forth in SEQ ID NO: 21 ; and(G) the VH FR4 set forth in SEQ ID NO: 22.

38. The antibody or antigen binding fragment of claim 21, wherein:(i) the VL comprises:(a) the CDRL1 set forth in SEQ ID NO: 7;(c) the CDRL3 set forth in SEQ ID NO: 9;(d) the VL FR1 set forth in SEQ ID NO: 23;(e) the VL FR2 set forth in SEQ ID NO: 28;(f) the VL FR3 set forth in SEQ ID NO: 30; and(g) the VL FR4 set forth in SEQ ID NO: 18; and(ii) the VH comprises:(B) the CDRH2 set forth in SEQ ID NO: 12;(C) the CDRH3 set forth in SEQ ID NO: 13;(D) the VH FR1 set forth in SEQ ID NO: 33;(E) the VH FR2 set forth in SEQ ID NO: 20;(F) the VH FR3 set forth in SEQ ID NO: 21 ; and(G) the VH FR4 set forth in SEQ ID NO: 22.

39. The antibody or antigen binding fragment of claim 21, wherein:(i) the VL comprises:(a) the CDRL1 set forth in SEQ ID NO: 7;(c) the CDRL3 set forth in SEQ ID NO: 9;(d) the VL FR1 set forth in SEQ ID NO: 23;(e) the VL FR2 set forth in SEQ ID NO: 28;(f) the VL FR3 set forth in SEQ ID NO: 30; and201FH13167949.1BPX-05925(g) the VL FR4 set forth in SEQ ID NO: 18; and(ii) the VH comprises:(B) the CDRH2 set forth in SEQ ID NO: 12;(C) the CDRH3 set forth in SEQ ID NO: 14;(D) the VH FR1 set forth in SEQ ID NO: 33;(E) the VH FR2 set forth in SEQ ID NO: 20;(F) the VH FR3 set forth in SEQ ID NO: 21 ; and(G) the VH FR4 set forth in SEQ ID NO: 22.

40. The antibody or antigen binding fragment of claim 21, wherein:(i) the VL comprises:(a) the CDRL1 set forth in SEQ ID NO: 8;(c) the CDRL3 set forth in SEQ ID NO: 9;(d) the VL FR1 set forth in SEQ ID NO: 23;(e) the VL FR2 set forth in SEQ ID NO: 28;(f) the VL FR3 set forth in SEQ ID NO: 30; and(g) the VL FR4 set forth in SEQ ID NO: 18; and(ii) the VH comprises:(B) the CDRH2 set forth in SEQ ID NO: 12;(C) the CDRH3 set forth in SEQ ID NO: 14;(D) the VH FR1 set forth in SEQ ID NO: 33;(E) the VH FR2 set forth in SEQ ID NO: 20;(F) the VH FR3 set forth in SEQ ID NO: 21 ; and(G) the VH FR4 set forth in SEQ ID NO: 22.

41. The antibody or antigen binding fragment of claim 21, wherein:(i) the VL comprises:(a) the CDRL1 set forth in SEQ ID NO: 8;(c) the CDRL3 set forth in SEQ ID NO: 9;(d) the VL FR1 set forth in SEQ ID NO: 24;(e) the VL FR2 set forth in SEQ ID NO: 28;(f) the VL FR3 set forth in SEQ ID NO: 30; and202FH13167949.1BPX-05925(g) the VL FR4 set forth in SEQ ID NO: 18; and(ii) the VH comprises:(B) the CDRH2 set forth in SEQ ID NO: 12;(C) the CDRH3 set forth in SEQ ID NO: 14;(D) the VH FR1 set forth in SEQ ID NO: 33;(E) the VH FR2 set forth in SEQ ID NO: 20;(F) the VH FR3 set forth in SEQ ID NO: 21 ; and(G) the VH FR4 set forth in SEQ ID NO: 22.

42. The antibody or antigen binding fragment of claim 21, wherein:(i) the VL comprises:(a) the CDRL1 set forth in SEQ ID NO: 7;(c) the CDRL3 set forth in SEQ ID NO: 9;(d) the VL FR1 set forth in SEQ ID NO: 24;(e) the VL FR2 set forth in SEQ ID NO: 28;(f) the VL FR3 set forth in SEQ ID NO: 30; and(g) the VL FR4 set forth in SEQ ID NO: 18; and(ii) the VH comprises:(B) the CDRH2 set forth in SEQ ID NO: 12;(C) the CDRH3 set forth in SEQ ID NO: 14;(D) the VH FR1 set forth in SEQ ID NO: 33;(E) the VH FR2 set forth in SEQ ID NO: 20;(F) the VH FR3 set forth in SEQ ID NO: 21 ; and(G) the VH FR4 set forth in SEQ ID NO: 22.

43. The antibody or antigen binding fragment of claim 21, wherein:(i) the VL comprises:(a) the CDRL1 set forth in SEQ ID NO: 8;(c) the CDRL3 set forth in SEQ ID NO: 10;(d) the VL FR1 set forth in SEQ ID NO: 24;(e) the VL FR2 set forth in SEQ ID NO: 28;(f) the VL FR3 set forth in SEQ ID NO: 30; and203FH13167949.1BPX-05925(g) the VL FR4 set forth in SEQ ID NO: 18; and(ii) the VH comprises:(B) the CDRH2 set forth in SEQ ID NO: 12;(C) the CDRH3 set forth in SEQ ID NO: 14;(D) the VH FR1 set forth in SEQ ID NO: 33;(E) the VH FR2 set forth in SEQ ID NO: 20;(F) the VH FR3 set forth in SEQ ID NO: 21 ; and(G) the VH FR4 set forth in SEQ ID NO: 22.

44. The antibody or antigen binding fragment of claim 21, wherein:(i) the VL comprises:(a) the CDRL1 set forth in SEQ ID NO: 7;(c) the CDRL3 set forth in SEQ ID NO: 10;(d) the VL FR1 set forth in SEQ ID NO: 24;(e) the VL FR2 set forth in SEQ ID NO: 28;(f) the VL FR3 set forth in SEQ ID NO: 30; and(g) the VL FR4 set forth in SEQ ID NO: 18; and(ii) the VH comprises:(B) the CDRH2 set forth in SEQ ID NO: 12;(C) the CDRH3 set forth in SEQ ID NO: 14;(D) the VH FR1 set forth in SEQ ID NO: 33;(E) the VH FR2 set forth in SEQ ID NO: 20;(F) the VH FR3 set forth in SEQ ID NO: 21 ; and(G) the VH FR4 set forth in SEQ ID NO: 22.

45. The antibody or antigen binding fragment of claim 21, wherein:(i) the VL comprises:(a) the CDRL1 set forth in SEQ ID NO: 7;(c) the CDRL3 set forth in SEQ ID NO: 9;(d) the VL FR1 set forth in SEQ ID NO: 24;(e) the VL FR2 set forth in SEQ ID NO: 28;(f) the VL FR3 set forth in SEQ ID NO: 30; and204FH13167949.1BPX-05925(g) the VL FR4 set forth in SEQ ID NO: 18; and(ii) the VH comprises:(B) the CDRH2 set forth in SEQ ID NO: 11 ;(C) the CDRH3 set forth in SEQ ID NO: 13;(D) the VH FR1 set forth in SEQ ID NO: 33;(E) the VH FR2 set forth in SEQ ID NO: 20;(F) the VH FR3 set forth in SEQ ID NO: 21 ; and(G) the VH FR4 set forth in SEQ ID NO: 22.

46. The antibody or antigen binding fragment of claim 21, wherein:(i) the VL comprises:(a) the CDRL1 set forth in SEQ ID NO: 7;(c) the CDRL3 set forth in SEQ ID NO: 9;(d) the VL FR1 set forth in SEQ ID NO: 24;(e) the VL FR2 set forth in SEQ ID NO: 28;(f) the VL FR3 set forth in SEQ ID NO: 30; and(g) the VL FR4 set forth in SEQ ID NO: 18; and(ii) the VH comprises:(B) the CDRH2 set forth in SEQ ID NO: 12;(C) the CDRH3 set forth in SEQ ID NO: 13;(D) the VH FR1 set forth in SEQ ID NO: 33;(E) the VH FR2 set forth in SEQ ID NO: 20;(F) the VH FR3 set forth in SEQ ID NO: 21 ; and(G) the VH FR4 set forth in SEQ ID NO: 22.

47. The antibody or antigen binding fragment of claim 21, wherein:(i) the VL comprises:(a) the CDRL1 set forth in SEQ ID NO: 7;(c) the CDRL3 set forth in SEQ ID NO: 10;(d) the VL FR1 set forth in SEQ ID NO: 24;(e) the VL FR2 set forth in SEQ ID NO: 28;(f) the VL FR3 set forth in SEQ ID NO: 30; and205FH13167949.1BPX-05925(g) the VL FR4 set forth in SEQ ID NO: 18; and(ii) the VH comprises:(B) the CDRH2 set forth in SEQ ID NO: 12;(C) the CDRH3 set forth in SEQ ID NO: 13;(D) the VH FR1 set forth in SEQ ID NO: 33;(E) the VH FR2 set forth in SEQ ID NO: 20;(F) the VH FR3 set forth in SEQ ID NO: 21 ; and(G) the VH FR4 set forth in SEQ ID NO: 22.

48. The antibody or antigen binding fragment of claim 21, wherein:(i) the VL comprises:(a) the CDRL1 set forth in SEQ ID NO: 8;(c) the CDRL3 set forth in SEQ ID NO: 190;(d) the VL FR1 set forth in SEQ ID NO: 24;(e) the VL FR2 set forth in SEQ ID NO: 28;(f) the VL FR3 set forth in SEQ ID NO: 192(GVPSRF S S SGHGTDFTFTIS SMQPED VATYYC) ; and(g) the VL FR4 set forth in SEQ ID NO: 18; and(ii) the VH comprises:(B) the CDRH2 set forth in SEQ ID NO: 12;(C) the CDRH3 set forth in SEQ ID NO: 14;(D) the VH FR1 set forth in SEQ ID NO: 33;(E) the VH FR2 set forth in SEQ ID NO: 20;(F) the VH FR3 set forth in SEQ ID NO: 21 ; and(G) the VH FR4 set forth in SEQ ID NO: 22.

49. The antibody or antigen binding fragment of claim 21, wherein:(i) the VL comprises:(a) the CDRL1 set forth in SEQ ID NO: 188;(c) the CDRL3 set forth in SEQ ID NO: 190;(d) the VL FR1 set forth in SEQ ID NO: 24;(e) the VL FR2 set forth in SEQ ID NO: 28;206FH13167949.1BPX-05925(f) the VL FR3 set forth in SEQ ID NO: 192; and(g) the VL FR4 set forth in SEQ ID NO: 18; and(ii) the VH comprises:(B) the CDRH2 set forth in SEQ ID NO: 12;(C) the CDRH3 set forth in SEQ ID NO: 14;(D) the VH FR1 set forth in SEQ ID NO: 33;(E) the VH FR2 set forth in SEQ ID NO: 20;(F) the VH FR3 set forth in SEQ ID NO: 21 ; and(G) the VH FR4 set forth in SEQ ID NO: 22.

50. The antibody or antigen binding fragment of claim 21, wherein:(i) the VL comprises:(a) the CDRL1 set forth in SEQ ID NO: 8;(c) the CDRL3 set forth in SEQ ID NO: 190;(d) the VL FR1 set forth in SEQ ID NO: 24;(e) the VL FR2 set forth in SEQ ID NO: 28;(f) the VL FR3 set forth in SEQ ID NO: 192; and(g) the VL FR4 set forth in SEQ ID NO: 18; and(ii) the VH comprises:(B) the CDRH2 set forth in SEQ ID NO: 12;(C) the CDRH3 set forth in SEQ ID NO: 191;(D) the VH FR1 set forth in SEQ ID NO: 33;(E) the VH FR2 set forth in SEQ ID NO: 20;(F) the VH FR3 set forth in SEQ ID NO: 21 ; and(G) the VH FR4 set forth in SEQ ID NO: 22.

51. The antibody or antigen binding fragment of claim 21, wherein the VH and the VL comprise amino acid sequences having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequences selected from:(a) SEQ ID NOs: 35 and 40, respectively;(b) SEQ ID NOs: 35 and 49, respectively;207FH13167949.1BPX-05925(c) SEQ ID NOs: 35 and 50, respectively;(d) SEQ ID NOs: 35 and 41, respectively;(e) SEQ ID NOs: 35 and 46, respectively;(f) SEQ ID NOs: 36 and 50, respectively;(g) SEQ ID NOs: 36 and 40, respectively;(h) SEQ ID NOs: 36 and 41, respectively;(i) SEQ ID NOs: 36 and 42, respectively;(j) SEQ ID NOs: 36 and 43, respectively;(k) SEQ ID NOs: 36 and 44, respectively;(l) SEQ ID NOs: 37 and 50, respectively;(m) SEQ ID NOs: 37 and 40, respectively;(n) SEQ ID NOs: 37 and 46, respectively;(o) SEQ ID NOs: 37 and 48, respectively;(p) SEQ ID NOs: 38 and 50, respectively;(q) SEQ ID NOs: 38 and 51, respectively;(r) SEQ ID NOs: 38 and 52, respectively;(s) SEQ ID NOs: 38 and 40, respectively;(t) SEQ ID NOs: 38 and 41, respectively;(u) SEQ ID NOs: 38 and 45, respectively;(v) SEQ ID NOs: 38 and 46, respectively;(w) SEQ ID NOs: 38 and 47, respectively;(x) SEQ ID NOs: 38 and 48, respectively;(y) SEQ ID NOs: 39 and 40, respectively;(z) SEQ ID NOs: 38 and 195, respectively;(aa) SEQ ID NOs: 38 and 196, respectively;(bb) SEQ ID NOs: 38 and 197, respectively;(cc) SEQ ID NOs: 194 and 41, respectively;(dd) SEQ ID NOs: 194 and 195, respectively;(ee) SEQ ID NOs: 38 and 198, respectively;(ff) SEQ ID NOs: 38 and 199, respectively;(gg) SEQ ID NOs: 194 and 197, respectively;(hh) SEQ ID NOs: 38 and 200, respectively;208FH13167949.1BPX-05925(ii) SEQ ID NOs: 38 and 201, respectively;(jj) SEQ ID NOs: 194 and 200, respectively;(kk) SEQ ID NOs: 38 and 202, respectively;(11) SEQ ID NOs: 38 and 203, respectively; and(mm) SEQ ID NOs: 194 and 202, respectively.

52. The antibody or antigen binding fragment of claim 21, wherein the VH and the VL comprise the amino acid sequences selected from:(a) SEQ ID NOs: 35 and 40, respectively;(b) SEQ ID NOs: 35 and 49, respectively;(c) SEQ ID NOs: 35 and 50, respectively;(d) SEQ ID NOs: 35 and 41, respectively;(e) SEQ ID NOs: 35 and 46, respectively;(f) SEQ ID NOs: 36 and 50, respectively;(g) SEQ ID NOs: 36 and 40, respectively;(h) SEQ ID NOs: 36 and 41, respectively;(i) SEQ ID NOs: 36 and 42, respectively;(j) SEQ ID NOs: 36 and 43, respectively;(k) SEQ ID NOs: 36 and 44, respectively;(l) SEQ ID NOs: 37 and 50, respectively;(m) SEQ ID NOs: 37 and 40, respectively;(n) SEQ ID NOs: 37 and 46, respectively;(o) SEQ ID NOs: 37 and 48, respectively;(p) SEQ ID NOs: 38 and 50, respectively;(q) SEQ ID NOs: 38 and 51, respectively;(r) SEQ ID NOs: 38 and 52, respectively;(s) SEQ ID NOs: 38 and 40, respectively;(t) SEQ ID NOs: 38 and 41, respectively;(u) SEQ ID NOs: 38 and 45, respectively;(v) SEQ ID NOs: 38 and 46, respectively;(w) SEQ ID NOs: 38 and 47, respectively;(x) SEQ ID NOs: 38 and 48, respectively;209FH13167949.1BPX-05925(y) SEQ ID NOs: 39 and 40, respectively(z) SEQ ID NOs: 38 and 195, respectively;(aa) SEQ ID NOs: 38 and 196, respectively;(bb) SEQ ID NOs: 38 and 197, respectively;(cc) SEQ ID NOs: 194 and 41, respectively;(dd) SEQ ID NOs: 194 and 195, respectively;(ee) SEQ ID NOs: 38 and 198, respectively;(ff) SEQ ID NOs: 38 and 199, respectively;(gg) SEQ ID NOs: 194 and 197, respectively;(hh) SEQ ID NOs: 38 and 200, respectively;(ii) SEQ ID NOs: 38 and 201, respectively;(jj) SEQ ID NOs: 194 and 200, respectively;(kk) SEQ ID NOs: 38 and 202, respectively;(11) SEQ ID NOs: 38 and 203, respectively; and(mm) SEQ ID NOs: 194 and 202, respectively.

53. The antibody or antigen binding fragment of any one of claims 1-52, comprising a heavy chain constant region.

54. The antibody or antigen binding fragment of claim 53, wherein the heavy chain constant region is an IgG constant region.

55. The antibody or antigen binding fragment of claim 54, wherein the IgG constant region is a wild-type IgG constant region.

56. The antibody or antigen binding fragment of claim 54, wherein the IgG constant region comprises at least one mutation relative to a wild-type IgG constant region.

57. The antibody or antigen binding fragment of any one of claims 54-56, wherein the IgG constant region is an IgGl, IgG2, IgG3, or IgG4 constant region.210FH13167949.1BPX-0592558. The antibody or antigen binding fragment of claim 57, wherein the IgG constant region is an IgGl constant region.

59. The antibody or antigen binding fragment of claim 57, wherein the IgGl constant region is a wild-type human IgGl constant region.

60. The antibody or antigen binding fragment of claim 57, wherein the IgGl constant region comprises at least one amino acid substitution relative to a wild-type human IgGl constant region.

61. The antibody or antigen binding fragment of claim 58, wherein the IgGl constant region comprises at least one amino acid substitution selected from: L234A, L235A, L235E, H268Q, V309L, A330S, P331S, and any combination thereof, relative to a wild-type human IgGl constant region, according to EU numbering.

62. The antibody or antigen binding fragment of claim 58 or 61, wherein the IgGl constant region comprises at least one amino acid substitution selected from: M252Y, S264T, T256E, M428L, N434S, and any combination thereof, relative to a wild-type human IgGl constant region, according to EU numbering.

63. The antibody or antigen binding fragment of any one of claims 58 and 61-62, wherein the IgGl constant region comprises an N297A, N297Q or N297G amino acid substitution relative to a wild-type human IgGl constant region, according to EU numbering.

64. The antibody or antigen binding fragment of claim 58, wherein the IgGl constant region comprises an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to an amino acid sequence selected from SEQ ID NOs: 171-176.

65. The antibody or antigen binding fragment of claim 57, wherein the IgG2 constant region is a wild-type human IgG2 constant region.

66. The antibody or antigen binding fragment of claim 57, wherein the IgG2 constant region comprises at least one amino acid substitution selected from: H268Q, V309L, A330S, P331S,211FH13167949.1BPX-05925V234A, G237A, P238S, H268A, and any combination thereof, relative to a wild-type human IgG2 constant region, according to EU numbering.

67. The antibody or antigen binding fragment of any one of claims 57 and 65, wherein the IgG2 constant region comprises an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to the amino acid sequence of SEQ ID NO: 177.

68. The antibody or antigen binding fragment of claim 57, wherein the IgG3 constant region is a wild-type human IgG3 constant region.

69. The antibody or antigen binding fragment of any one of claims 57 and 68, wherein the IgG3 constant region comprises an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to the amino acid sequence of SEQ ID NO: 178.

70. The antibody or antigen binding fragment of claim 57, wherein the IgG4 constant region is a wild-type human IgG4 constant region.

71. The antibody or antigen binding fragment of claim 57, wherein the IgG4 constant region comprises an F234A and / or an L235A amino acid substitution relative to a wild-type human IgG4 constant region, according to EU numbering.

72. The antibody or antigen binding fragment of any one of claims 57 and 70, wherein the IgG4 constant region comprises an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to the amino acid sequence of SEQ ID NO: 179.

73. The antibody or antigen binding fragment of any one of claims 1-72, comprising a light chain constant region.

74. The antibody or antigen binding fragment of claim 73, wherein the light chain constant region is a kappa light chain or a lambda light chain.212FH13167949.1BPX-0592575. The antibody or antigen binding fragment of claim 74, wherein the kappa light chain comprises an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to the amino acid sequence of SEQ ID NO: 180.

76. The antibody or antigen binding fragment of claim 74, wherein the lambda light chain comprises an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to the amino acid sequence of SEQ ID NO: 181.

77. The antibody or antigen binding fragment of any one of claims 1-76, comprising a heavy chain sequence and a light chain sequence comprising amino acid sequences having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequences selected from:(a) SEQ ID NOs: 53 and 58, respectively;(b) SEQ ID NOs: 53 and 70, respectively;(c) SEQ ID NOs: 53 and 67, respectively;(d) SEQ ID NOs: 53 and 66, respectively;(e) SEQ ID NOs: 53 and 63, respectively;(f) SEQ ID NOs: 54 and 58, respectively;(g) SEQ ID NOs: 54 and 66, respectively;(h) SEQ ID NOs: 54 and 59, respectively;(i) SEQ ID NOs: 54 and 60, respectively;(j) SEQ ID NOs: 54 and 61, respectively;(k) SEQ ID NOs: 54 and 67, respectively;(l) SEQ ID NOs: 55 and 58, respectively;(m) SEQ ID NOs: 55 and 63, respectively;(n) SEQ ID NOs: 55 and 65, respectively;(o) SEQ ID NOs: 55 and 67, respectively;(p) SEQ ID NOs: 56 and 67, respectively;(q) SEQ ID NOs: 56 and 68, respectively;(r) SEQ ID NOs: 56 and 69, respectively;(s) SEQ ID NOs: 56 and 58, respectively;(t) SEQ ID NOs: 56 and 66, respectively;213FH13167949.1BPX-05925(u) SEQ ID NOs: 56 and 62, respectively;(v) SEQ ID NOs: 56 and 63, respectively;(w) SEQ ID NOs: 56 and 64, respectively;(x) SEQ ID NOs: 56 and 65, respectively;(y) SEQ ID NOs: 57 and 58, respectively;(z) SEQ ID NOs: 56 and 205, respectively;(aa) SEQ ID NOs: 56 and 206, respectively;(bb) SEQ ID NOs: 56 and 207, respectively;(cc) SEQ ID NOs: 204 and 66, respectively;(dd) SEQ ID NOs: 204 and 205, respectively;(ee) SEQ ID NOs: 56 and 208, respectively;(ff) SEQ ID NOs: 56 and 209, respectively;(gg) SEQ ID NOs: 204 and 207, respectively;(hh) SEQ ID NOs: 56 and 210, respectively;(ii) SEQ ID NOs: 56 and 211, respectively;(jj) SEQ ID NOs: 204 and 210, respectively;(kk) SEQ ID NOs: 56 and 212, respectively;(11) SEQ ID NOs: 56 and 213, respectively; and(mm) SEQ ID NOs: 204 and 212, respectively.

78. The antibody or antigen binding fragment of any one of claims 1-76, comprising a heavy chain sequence and a light chain sequence comprising the amino acid sequences selected from:(a) SEQ ID NOs: 53 and 58, respectively;(b) SEQ ID NOs: 53 and 70, respectively;(c) SEQ ID NOs: 53 and 67, respectively;(d) SEQ ID NOs: 53 and 66, respectively;(e) SEQ ID NOs: 53 and 63, respectively;(f) SEQ ID NOs: 54 and 58, respectively;(g) SEQ ID NOs: 54 and 66, respectively;(h) SEQ ID NOs: 54 and 59, respectively;(i) SEQ ID NOs: 54 and 60, respectively;(j) SEQ ID NOs: 54 and 61, respectively;214FH13167949.1BPX-05925(k) SEQ ID NOs: 54 and 67, respectively;(l) SEQ ID NOs: 55 and 58, respectively;(m) SEQ ID NOs: 55 and 63, respectively;(n) SEQ ID NOs: 55 and 65, respectively;(o) SEQ ID NOs: 55 and 67, respectively;(p) SEQ ID NOs: 56 and 67, respectively;(q) SEQ ID NOs: 56 and 68, respectively;(r) SEQ ID NOs: 56 and 69, respectively;(s) SEQ ID NOs: 56 and 58, respectively;(t) SEQ ID NOs: 56 and 66, respectively;(u) SEQ ID NOs: 56 and 62, respectively;(v) SEQ ID NOs: 56 and 63, respectively;(w) SEQ ID NOs: 56 and 64, respectively;(x) SEQ ID NOs: 56 and 65, respectively;(y) SEQ ID NOs: 57 and 58, respectively(z) SEQ ID NOs: 56 and 205, respectively;(aa) SEQ ID NOs: 56 and 206, respectively;(bb) SEQ ID NOs: 56 and 207, respectively;(cc) SEQ ID NOs: 204 and 66, respectively;(dd) SEQ ID NOs: 204 and 205, respectively;(ee) SEQ ID NOs: 56 and 208, respectively;(ff) SEQ ID NOs: 56 and 209, respectively;(gg) SEQ ID NOs: 204 and 207, respectively;(hh) SEQ ID NOs: 56 and 210, respectively;(ii) SEQ ID NOs: 56 and 211, respectively;(jj) SEQ ID NOs: 204 and 210, respectively;(kk) SEQ ID NOs: 56 and 212, respectively;(11) SEQ ID NOs: 56 and 213, respectively; and(mm) SEQ ID NOs: 204 and 212, respectively.

79. A conjugate comprising (i) the antibody or antigen binding fragment of any one of claims 1-78, and (ii) at least one regulator of complement activation (RCA) polypeptide.215FH13167949.1BPX-0592580. A conjugate comprising (i) an antibody, or antigen binding fragment thereof, that specifically binds C2, and (ii) at least one RCA polypeptide.

81. A conjugate comprising (i) a means for binding C2, and (ii) at least one RCA polypeptide.

82. The conjugate of any one of claims 79-81, wherein the RCA polypeptide comprises an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to an amino acid sequence selected from SEQ ID NOs: 89-104.

83. The conjugate of any one of claims 79-81, wherein the RCA polypeptide comprises an amino acid sequence selected from SEQ ID NOs: 89-104.

84. The conjugate of any one of claims 79-83, wherein the antibody or antigen binding fragment, or the means for binding C2, is conjugated to the at least one RCA polypeptide via a linker.

85. The conjugate of claim 84, wherein the linker is a peptide linker.

86. The conjugate of claim 85, wherein the peptide linker is a GlySer linker.

87. The conjugate of claim 86, wherein the GlySer linker is a (GxSy)zlinker, wherein x is 3-6, y is 0 or 1, and z is 1-5.

88. The conjugate of claim 87, wherein the GlySer linker is a (GGGGS), (GGGGS)(GGGGS) or (GGGGS)(GGGGS)(GGGGS) linker.

89. The conjugate of claim 86, wherein the GlySer linker is a (GGGGS)n(PGGGS)xlinker, wherein P is proline, a (GGGPS)n(GGGGS)xlinker, wherein P is proline, a (GGGGA)n(GGGGS)xlinker, wherein A is alanine, or a (GGGGQ)n(GGGGS)xlinker, wherein Q is glutamine, where for each linker n is 1-3, and x is 0 or 1, optionally wherein n is 1 or 2.216FH13167949.1BPX-0592590. The conjugate of claim 85, wherein the peptide linker comprises an amino acid sequence selected from SEQ ID NOs: 105-168.

91. The conjugate of any one of claims 79-90, comprising two or more RCA polypeptides.

92. The conjugate of claim 91, wherein the two or more RCA polypeptides are the same.

93. The conjugate of claim 91, wherein the two or more RCA polypeptides are different.

94. The conjugate of claim 91, wherein the two or more RCA polypeptides are linked to each other via a linker.

95. The conjugate of claim 94, wherein the linker is a peptide linker.

96. The conjugate of claim 95, wherein the peptide linker is a GlySer linker.

97. The conjugate of claim 96, wherein the GlySer linker is a (GxSy)zlinker, wherein x is 3-6, y is 0 or 1, and z is 1-5.

98. The conjugate of claim 97, wherein the GlySer linker is a (GGGGS), (GGGGSj(GGGGS) or (GGGGS)(GGGGS)(GGGGS) linker.

99. The conjugate of claim 95, wherein the GlySer linker is a (GGGGS)n(PGGGS)xlinker, wherein P is proline, a (GGGPS)n(GGGGS)xlinker, wherein P is proline, a (GGGGA)n(GGGGS)xlinker, wherein A is alanine, or a (GGGGQ)n(GGGGS)xlinker, wherein Q is glutamine, where for each linker n is 1-3, and x is 0 or 1, optionally wherein n is 1 or 2.

100. The conjugate of any one of claims 91-99, wherein the peptide linker comprises an amino acid sequence selected from SEQ ID NOs: 105-168.

101. The conjugate of any one of claims 91-100, wherein the two or more RCA polypeptides independently comprise SEQ ID NOs: 89 and 93.217FH13167949.1BPX-05925102. The conjugate of any one of claims 79-101, wherein the at least one RCA polypeptide is conjugated to a heavy chain of the antibody or the means for binding C2.

103. The conjugate of any one of claims 79-101, wherein the at least one RCA polypeptide is conjugated to a light chain of the antibody or the means for binding C2.

104. A conjugate comprising the formula of: ANTIBODY-(LINKERlxi-RCAl)n-LINKER2x2- RCA2, wherein “ANTIBODY” is the antibody or antigen binding fragment of any one of claims 1 - 76, or an antibody or antigen binding fragment thereof that specifically binds C2; wherein “LINKER1” and “LINKER2” are each independently a peptide linker; wherein “RCA1” and “RCA2” are each independently an RCA polypeptide; and wherein "n" is 0-5, XI is independently 0 or 1 and X2 is 0 or 1.

105. The conjugate of claim 104, wherein RCA1 and RCA2 are each independently selected from SEQ ID NOs: 89-104.

106. The conjugate of claim 104, wherein RCA1 and RCA2 are each independently selected from SEQ ID NOs: 89, 93, or 97, and “n” is 1 and XI and X2 are each 1 or wherein RCA2 is SEQ ID NOs: 89, 93, or 97, and “n” is 0 and X2 is 1.

107. The conjugate of any one of claims 104-106, wherein LINKER1 and LINKER2 are each a GlySer linker.

108. The conjugate of any one of claims 104-106, wherein LINKER1 and LINKER2 are each independently a (GxSy)zlinker, wherein x is 3-6, y is 0 or 1, and z is 1-5.

109. The conjugate of claim 108, wherein LINKER1 and LINKER2 are each independently a (GGGGS), (GGGGSj(GGGGS) or (GGGGS)(GGGGS)(GGGGS) linker.218FH13167949.1BPX-05925110. The conjugate of any one of claims 104-106, wherein LINKER! and LINKER2 are each independently a (GGGGS)n(PGGGS)xlinker, wherein P is proline, a (GGGGS)n(PGGGS)xlinker where P is proline, a (GGGPS)n(GGGGS)xlinker, wherein P is proline, a (GGGGA)n(GGGGS)xlinker, wherein A is alanine, or a (GGGGQ)n(GGGGS)xlinker, wherein Q is glutamine, where for each linker n is 1-3, and x is 0 or 1, optionally wherein n is 1 or 2.

111. The conjugate of any one of claims 104-106, wherein LINKER1 and LINKER2 are each independently selected from SEQ ID NOs: 105-168.

112. A conjugate comprising a heavy chain comprising an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to an amino acid sequence selected from SEQ ID NOs: 71-88 and a light chain comprising an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to an amino acid sequence selected from SEQ ID NOs: 58-70.

113. A conjugate comprising a heavy chain comprising an amino acid sequence selected from SEQ ID NOs: 71-88, and a light chain comprising an amino acid sequence selected from SEQ ID NOs: 58-70.

114. A conjugate comprising a heavy chain and a light chain comprising amino acid sequences having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequences selected from:(a) SEQ ID NOs: 71 and 67, respectively;(b) SEQ ID NOs: 71 and 58, respectively;(c) SEQ ID NOs: 72 and 58, respectively;(d) SEQ ID NOs: 72 and 67, respectively;(e) SEQ ID NOs: 72 and 66, respectively;(f) SEQ ID NOs: 73 and 68, respectively;(g) SEQ ID NOs: 73 and 62, respectively;(h) SEQ ID NOs: 73 and 64, respectively;(i) SEQ ID NOs: 73 and 63, respectively;(j) SEQ ID NOs: 73 and 65, respectively;219FH13167949.1BPX-05925(k) SEQ ID NOs: 73 and 66, respectively;(l) SEQ ID NOs: 74 and 58, respectively;(m) SEQ ID NOs: 75 and 58, respectively;(n) SEQ ID NOs: 76 and 58, respectively;(o) SEQ ID NOs: 76 and 63, respectively;(p) SEQ ID NOs: 77 and 58, respectively;(q) SEQ ID NOs: 77 and 63, respectively;(r) SEQ ID NOs: 78 and 58, respectively;(s) SEQ ID NOs: 78 and 63, respectively;(t) SEQ ID NOs: 79 and 63, respectively;(u) SEQ ID NOs: 79 and 65, respectively;(v) SEQ ID NOs: 80 and 63, respectively;(w) SEQ ID NOs: 80 and 65, respectively;(x) SEQ ID NOs: 81 and 63, respectively;(y) SEQ ID NOs: 81 and 65, respectively;(z) SEQ ID NOs: 82 and 63, respectively;(aa) SEQ ID NOs: 83 and 63, respectively;(bb) SEQ ID NOs: 83 and 66, respectively;(cc) SEQ ID NOs: 84 and 63, respectively;(dd) SEQ ID NOs: 85 and 58, respectively;(ee) SEQ ID NOs: 86 and 63, respectively;(ff) SEQ ID NOs: 86 and 66, respectively;(gg) SEQ ID NOs: 86 and 65, respectively;(hh) SEQ ID NOs: 87 and 58, respectively;(ii) SEQ ID NOs: 88 and 63, respectively;(jj) SEQ ID NOs: 88 and 66, respectively; and(kk) SEQ ID NOs: 88 and 65, respectively.

115. A conjugate comprising a heavy chain and a light chain comprising the amino acid sequences selected from:(a) SEQ ID NOs: 71 and 67, respectively;(b) SEQ ID NOs: 71 and 58, respectively;220FH13167949.1BPX-05925(c) SEQ ID NOs: 72 and 58, respectively;(d) SEQ ID NOs: 72 and 67, respectively;(e) SEQ ID NOs: 72 and 66, respectively;(f) SEQ ID NOs: 73 and 68, respectively;(g) SEQ ID NOs: 73 and 62, respectively;(h) SEQ ID NOs: 73 and 64, respectively;(i) SEQ ID NOs: 73 and 63, respectively;(j) SEQ ID NOs: 73 and 65, respectively;(k) SEQ ID NOs: 73 and 66, respectively;(l) SEQ ID NOs: 74 and 58, respectively;(m) SEQ ID NOs: 75 and 58, respectively;(n) SEQ ID NOs: 76 and 58, respectively;(o) SEQ ID NOs: 76 and 63, respectively;(p) SEQ ID NOs: 77 and 58, respectively;(q) SEQ ID NOs: 77 and 63, respectively;(r) SEQ ID NOs: 78 and 58, respectively;(s) SEQ ID NOs: 78 and 63, respectively;(t) SEQ ID NOs: 79 and 63, respectively;(u) SEQ ID NOs: 79 and 65, respectively;(v) SEQ ID NOs: 80 and 63, respectively;(w) SEQ ID NOs: 80 and 65, respectively;(x) SEQ ID NOs: 81 and 63, respectively;(y) SEQ ID NOs: 81 and 65, respectively;(z) SEQ ID NOs: 82 and 63, respectively;(aa) SEQ ID NOs: 83 and 63, respectively;(bb) SEQ ID NOs: 83 and 66, respectively;(cc) SEQ ID NOs: 84 and 63, respectively;(dd) SEQ ID NOs: 85 and 58, respectively;(ee) SEQ ID NOs: 86 and 63, respectively;(ff) SEQ ID NOs: 86 and 66, respectively;(gg) SEQ ID NOs: 86 and 65, respectively;(hh) SEQ ID NOs: 87 and 58, respectively;221FH13167949.1BPX-05925(ii) SEQ ID NOs: 88 and 63, respectively;(jj) SEQ ID NOs: 88 and 66, respectively; and(kk) SEQ ID NOs: 88 and 65, respectively.

116. A composition comprising the antibody or antigen binding fragment of any one of claims 1- 78.

117. A composition comprising the conjugate of any one of claims 79-115.

118. The composition of claim 116 or 117, comprising a pharmaceutically acceptable carrier.

119. A nucleic acid comprising a nucleotide sequence encoding the VL, the VH, the heavy chain, the light chain, or any combination thereof, of the antibody or antigen binding fragment of any one of claims 1-78.

120. A nucleic acid comprising a nucleotide sequence encoding the conjugate of any one of claims 79-115.

121. An expression vector comprising the nucleic acid of claim 119 or 120.

122. A cell comprising the expression vector of claim 121.

123. A method for producing the antibody or antigen binding fragment of any one of claims 1-78 or the conjugate of any one of claims 79-115, the method comprising maintaining the cell of claim 122 under conditions permitting expression of the antibody or antigen binding fragment, or the conjugate.

124. A method for treating a complement-associated disease or disorder in a subject, comprising administering to the subject the antibody or antigen binding fragment of any one of claims 1-78, the conjugate of any one of claims 79-115, or the composition of any one of claims 116-118.222FH13167949.1BPX-05925125. The method of claim 124, wherein the complement-associated disease or disorder is selected from amyotrophic lateral sclerosis (ALS), antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis, atypical hemolytic uremic syndrome (aHUS), aHUS after kidney transplant, autoimmune encephalitis, bullous pemphigoid, C3 glomerulopathy (C3G), C3 glomerulonephritis (C3GN), C3G relapse after kidney transplant, cold agglutinin disease (CAD), CD59 deficiency, CD59-mediated hemolytic anemia with or without immune-mediated polyneuropathy, CHAPLE syndrome (CD55 deficiency), chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), complement Factor I deficiency, diabetic nephropathy, cryoglobulinemia, dense deposit disease, diabetic lumbosacral plexopathy, age-related macular degeneration (AMD), glaucoma, dry AMD, wet AMD, diabetic retinopathy, inherited retinal disease, retinal detachment, familial amyloid polyneuropathy, fibrillary glomerulonephritis, focal segmental glomerulosclerosis (FSGS), geographic atrophy, Goodpasture’s syndrome, Guillain-Barre syndrome, hematopoietic stem cell transplant-associated-thrombotic microangiopathy (HSCT-TMA), hidradenitis suppurativa, Huntington's disease, IgA nephropathy (IgAN), IGAN relapse after kidney transplant antibody mediated rejection (i.e., kidney transplant) post-transplant rejection (solid organ antibody mediated rejection), immune complex membranoproliferative glomerulonephritis (IC-MPGN), immune- mediated necrotizing myopathy, immunoglobulin A-associated vasculitis (IgAV), immunoglobulin A-associated vasculitis (IgAV) nephritis, immune thrombocytopenia (ITP), immune thrombocytopenic purpura, lupus nephritis, lupus nephritis flares with high urinary Ba or sCb5 -9, multiple sclerosis, multifocal motor neuropathy (MMN), myasthenia gravis, neuromyelitis optica spectrum disorder (NMOSD), paroxysmal nocturnal hemoglobinuria (PNH), post-infectious glomerulonephritis, primary membranous nephropathy (PMN), rhabdomyolysis-induced acute kidney injury (RIAKI), sickle cell disease, Sjogren's syndrome, tauopathy, thrombotic microangiopathy (TMA), systemic lupus erythematosus, thrombotic thrombocytopenic purpura (TTP), warm autoimmune hemolytic anemia (WAHA), acute spinal cord injuries, anti-MAG (myelin-associated glycoprotein) peripheral polyneuropathy (IgM neuropathy), pyoderma gangrenosum, dermatomyositis, hypocomplementemic urticarial vasculitis syndrome (HUVS), auto-immune chronic spontaneous urticaria (aiCUS), Kawasaki disease, Takayasu's arteritis, antiphospholipid therapy - thrombosis prevention (antiphospholipid syndrome), catastrophic antiphospholipid syndrome (CAPS), pre-eclampsia, HELLP syndrome, and autoimmune hepatitis (AIH).223FH13167949.1BPX-05925126. The method of claim 124, wherein the complement-associated disease or disorder is selected from cold agglutinin disease (CAD), atypical hemolytic uremic syndrome (aHUS), IgA nephropathy (IgAN), and lupus nephritis (LN).

127. The method of claim 124, wherein the complement-associated disease or disorder is selected from acute spinal cord injuries, CIDP, NMOSD, GBS, MMN, and IgM neuropathy.

128. The method of claim 124, wherein the complement-associated disease or disorder is selected from delayed graft function (i.e., kidney transplant), Goodpasture's Syndrome, and C3G.

129. The method of claim 124, wherein the complement-associated disease or disorder is selected from hidradenitis suppurativa, bullous pemphigoid, IgA Vasculitis, pyoderma gangrenosum, and dermatomyositis.

130. The method of claim 124, wherein the complement-associated disease or disorder is selected from myasthenia gravis, Behcet's disease, IgG4-related disease, HSCT-TMA, IMNM, HUVS, aiCSU, Kawasaki disease, and Takayasu's arteritis.

131. The method of claim 124, wherein the complement-associated disease or disorder is selected from antiphospholipid syndrome, CAD, CAPS, wAIHA, WAHA, post-transplant rejection (solid organ antibody mediated rejection), and antibody mediated rejection (i.e., kidney transplant).

132. The method of claim 124, wherein the complement-associated disease or disorder is selected from dermatomyositis or MMN.

133. The method of claim 124, wherein the complement-associated disease or disorder is selected from bullous pemphigoid or HUVS.

134. A kit comprising a container comprising the antibody or antigen binding fragment of any one of claims 1-78, or the conjugate of any one of claims 79-115, and an optional pharmaceutically acceptable carrier, and a package insert comprising instructions for administration of the antibody or antigen binding fragment, or the conjugate, to a subject in need thereof.224FH13167949.1BPX-05925135. The kit of claim 134, wherein the subject has a complement-associated disease or disorder.

136. The use of the antibody or antigen binding fragment of any one of claims 1-78, the conjugate of any one of claims 79-115, or the composition of any one of claims 116-118, for the manufacture of a medicament for treating a complement-associated disease or disorder in a subject.

137. The kit of claim 134 or 135 or the use of claim 136, wherein the complement-associated disease or disorder is selected from amyotrophic lateral sclerosis (ALS), antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis, atypical hemolytic uremic syndrome (aHUS), aHUS after kidney transplant, autoimmune encephalitis, bullous pemphigoid, C3 glomerulopathy (C3G),C3 glomerulonephritis (C3GN), C3G relapse after kidney transplant, cold agglutinin disease (CAD), CD59 deficiency, CD59-mediated hemolytic anemia with or without immune-mediated polyneuropathy, CHAPLE syndrome (CD55 deficiency), chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), complement Factor I deficiency, diabetic nephropathy, cryoglobulinemia, dense deposit disease, diabetic lumbosacral plexopathy, age-related macular degeneration (AMD), glaucoma, dry AMD, wet AMD, diabetic retinopathy, inherited retinal disease, retinal detachment, familial amyloid polyneuropathy, fibrillary glomerulonephritis, focal segmental glomerulosclerosis (FSGS), geographic atrophy, Goodpasture’s syndrome, Guillain- Barre syndrome, hematopoietic stem cell transplant-associated-thrombotic microangiopathy (HSCT-TMA), hidradenitis suppurativa, Huntington's disease, IgA nephropathy (IgAN), IGAN relapse after kidney transplant antibody mediated rejection (i.e., kidney transplant) post-transplant rejection (solid organ antibody mediated rejection), immune complex membranoproliferative glomerulonephritis (IC-MPGN), immune-mediated necrotizing myopathy, immunoglobulin A- associated vasculitis (IgAV), immunoglobulin A-associated vasculitis (IgAV) nephritis, immune thrombocytopenia (ITP), immune thrombocytopenic purpura, lupus nephritis, lupus nephritis flares with high urinary Ba or sCb5 -9, multiple sclerosis, multifocal motor neuropathy (MMN), myasthenia gravis, neuromyelitis optica spectrum disorder (NMOSD), paroxysmal nocturnal hemoglobinuria (PNH), post-infectious glomerulonephritis, primary membranous nephropathy (PMN), rhabdomyolysis-induced acute kidney injury (RIAKI), sickle cell disease, Sjogren's syndrome, tauopathy, thrombotic microangiopathy (TMA), systemic lupus erythematosus, thrombotic thrombocytopenic purpura (TTP), warm autoimmune hemolytic anemia (WAHA), acute 225FH13167949.1BPX-05925 spinal cord injuries, anti-MAG (myelin-associated glycoprotein) peripheral polyneuropathy (IgM neuropathy), pyoderma gangrenosum, dermatomyositis, hypocomplementemic urticarial vasculitis syndrome (HUVS), auto-immune chronic spontaneous urticaria (aiCUS), Kawasaki disease, Takayasu's arteritis, antiphospholipid therapy - thrombosis prevention (antiphospholipid syndrome), catastrophic antiphospholipid syndrome (CAPS), pre-eclampsia, HELLP syndrome, and autoimmune hepatitis (AIH).

138. The kit of claim 134 or 135 or the use of claim 136, wherein the complement-associated disease or disorder is selected from cold agglutinin disease (CAD), atypical hemolytic uremic syndrome (aHUS), IgA nephropathy (IgAN), and lupus nephritis (LN).

139. The kit of claim 134 or 135 or the use of claim 136, wherein the complement-associated disease or disorder is selected from acute spinal cord injuries, CIDP, NMOSD, GBS, MMN, and IgM neuropathy.

140. The kit of claim 134 or 135 or the use of claim 136, wherein the complement-associated disease or disorder is selected from delayed graft function (i.e., kidney transplant), Goodpasture's Syndrome, and C3G.

141. The kit of claim 134 or 135 or the use of claim 136, wherein the complement-associated disease or disorder is selected from hidradenitis suppurativa, bullous pemphigoid, IgA Vasculitis, pyoderma gangrenosum, and dermatomyositis.

142. The kit of claim 134 or 135 or the use of claim 136, wherein the complement-associated disease or disorder is selected from myasthenia gravis, Behcet's disease, IgG4-related disease, HSCT-TMA, IMNM, HUVS, aiCSU, Kawasaki disease, and Takayasu's arteritis.

143. The kit of claim 134 or 135 or the use of claim 136, wherein the complement-associated disease or disorder is selected from antiphospholipid syndrome, CAD, CAPS, wAIHA, WAHA, post-transplant rejection (solid organ antibody mediated rejection), and antibody mediated rejection (i.e., kidney transplant).226FH13167949.1BPX-05925144. The kit of claim 134 or 135 or the use of claim 136, wherein the complement-associated disease or disorder is selected from dermatomyositis or MMN.

145. The kit of claim 134 or 135 or the use of claim 136, wherein the complement-associated disease or disorder is selected from bullous pemphigoid or HUVS.227FH13167949.1