US2023382985A1PendingUtilityA1

C3-binding agents and methods of use thereof

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Assignee: NGM BIOPHARMACEUTICALS INCPriority: Apr 3, 2018Filed: Aug 10, 2023Published: Nov 30, 2023
Est. expiryApr 3, 2038(~11.7 yrs left)· nominal 20-yr term from priority
Inventors:Dana Yen Mei DueyZhonghao LiuJie TangYan WangYiyuan YinWenwu ZhaiJared Martin Higbee
C07K 16/18C07K 2317/24C07K 2317/31C07K 2317/92C07K 2317/622C07K 2317/624C07K 2317/76C07K 2317/565A61P 27/02C07K 2317/33C07K 2317/94A61K 2039/505
76
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Claims

Abstract

The present disclosure provides binding agents, such as antibodies (including single chain variable fragments), that specifically bind complement component C3, including human C3, compositions comprising same, and methods of their use. The disclosure also provides related polynucleotides and vectors encoding the binding agents and cells comprising same.

Claims

exact text as granted — not AI-modified
What is claimed: 
     
         1 . A binding agent that specifically binds human complement component C3 (C3), which comprises:
 (a) a heavy chain CDR1 comprising GYTFTDFYMD (SEQ ID NO:7); a heavy chain CDR2 comprising YIYPHNGGTTYNQNFTG (SEQ ID NO:8), YIYPHNGGTTYNQQFTG (SEQ ID NO:13), YIYPHNAGTTYNQQFTG (SEQ ID NO:14), YIYPHNTGTTYNQQFTG (SEQ ID NO:15), YIYPHEGGTTYNQQFTG (SEQ ID NO:16), or YIYPHQGGTTYNQQFTG (SEQ ID NO:17), and a heavy chain CDR3 comprising RGGFDFDY (SEQ ID NO:9); and/or   (b) a light chain CDR1 comprising KASENVDTYVS (SEQ ID NO:10); a light chain CDR2 comprising GASNRYT (SEQ ID NO:11); and a light chain CDR3 comprising GQSHSYPLT (SEQ ID NO:12).   
     
     
         2 . The binding agent of  claim 1 , which comprises:
 (a) a heavy chain CDR1 comprising GYTFTDFYMD (SEQ ID NO:7); a heavy chain CDR2 comprising YIYPHNGGTTYNQNFTG (SEQ ID NO:8), and a heavy chain CDR3 comprising RGGFDFDY (SEQ ID NO:9); and/or   (b) a light chain CDR1 comprising KASENVDTYVS (SEQ ID NO:10); a light chain CDR2 comprising GASNRYT (SEQ ID NO:11); and a light chain CDR3 comprising GQSHSYPLT (SEQ ID NO:12).   
     
     
         3 . The binding agent of  claim 1 , which comprises:
 (a) a heavy chain CDR1 comprising GYTFTDFYMD (SEQ ID NO:7); a heavy chain CDR2 comprising YIYPHNGGTTYNQQFTG (SEQ ID NO:13), and a heavy chain CDR3 comprising RGGFDFDY (SEQ ID NO:9); and/or   (b) a light chain CDR1 comprising KASENVDTYVS (SEQ ID NO:10); a light chain CDR2 comprising GASNRYT (SEQ ID NO:11); and a light chain CDR3 comprising GQSHSYPLT (SEQ ID NO:12).   
     
     
         4 . The binding agent of  claim 1 , which comprises:
 (a) a heavy chain CDR1 comprising GYTFTDFYMD (SEQ ID NO:7); a heavy chain CDR2 comprising YIYPHNAGTTYNQQFTG (SEQ ID NO:14), and a heavy chain CDR3 comprising RGGFDFDY (SEQ ID NO:9); and/or   (b) a light chain CDR1 comprising KASENVDTYVS (SEQ ID NO:10); a light chain CDR2 comprising GASNRYT (SEQ ID NO:11); and a light chain CDR3 comprising GQSHSYPLT (SEQ ID NO:12).   
     
     
         5 . The binding agent of  claim 1 , which comprises:
 (a) a heavy chain CDR1 comprising GYTFTDFYMD (SEQ ID NO:7); a heavy chain CDR2 comprising YIYPHNTGTTYNQQFTG (SEQ ID NO:15), and a heavy chain CDR3 comprising RGGFDFDY (SEQ ID NO:9); and/or   (b) a light chain CDR1 comprising KASENVDTYVS (SEQ ID NO:10); a light chain CDR2 comprising GASNRYT (SEQ ID NO:11); and a light chain CDR3 comprising GQSHSYPLT (SEQ ID NO:12).   
     
     
         6 . The binding agent of  claim 1 , which comprises:
 (a) a heavy chain variable region having at least 90% sequence identity to SEQ ID NO:18, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, or SEQ ID NO:24 and/or   (b) a light chain variable region having at least 90% sequence identity to SEQ ID NO:19 or SEQ ID NO:25.   
     
     
         7 . The binding agent of  claim 6 , which comprises a heavy chain variable region having at least 95% sequence identity to SEQ ID NO:18 and a light chain variable region having at least 95% sequence identity to SEQ ID NO:19. 
     
     
         8 . The binding agent of  claim 6 , which comprises a heavy chain variable region having at least 95% sequence identity to SEQ ID NO:20 and a light chain variable region having at least 95% sequence identity to SEQ ID NO:25. 
     
     
         9 . The binding agent of  claim 6 , which comprises a heavy chain variable region having at least 95% sequence identity to SEQ ID NO:21 and a light chain variable region having at least 95% sequence identity to SEQ ID NO:25. 
     
     
         10 . The binding agent of  claim 6 , which comprises a heavy chain variable region having at least 95% sequence identity to SEQ ID NO:22 and a light chain variable region having at least 95% sequence identity to SEQ ID NO:25. 
     
     
         11 . The binding agent of  claim 6 , which comprises a heavy chain variable region having at least 95% sequence identity to SEQ ID NO:23 and a light chain variable region having at least 95% sequence identity to SEQ ID NO:25. 
     
     
         12 . The binding agent of  claim 6 , which comprises a heavy chain variable region having at least 95% sequence identity to SEQ ID NO:24 and a light chain variable region having at least 95% sequence identity to SEQ ID NO:25. 
     
     
         13 . The binding agent of  claim 6 , which comprises a heavy chain variable region comprising SEQ ID NO:18 and a light chain variable region comprising SEQ ID NO:19. 
     
     
         14 . The binding agent of  claim 6 , which comprises a heavy chain variable region comprising SEQ ID NO:20 and a light chain variable region comprising SEQ ID NO:25. 
     
     
         15 . The binding agent of  claim 6 , which comprises a heavy chain variable region comprising SEQ ID NO:21 and a light chain variable region comprising SEQ ID NO:25. 
     
     
         16 . The binding agent of  claim 6 , which comprises a heavy chain variable region comprising SEQ ID NO:22 and a light chain variable region comprising SEQ ID NO:25. 
     
     
         17 . The binding agent of  claim 6 , which comprises a heavy chain variable region comprising SEQ ID NO:23 and a light chain variable region comprising SEQ ID NO:25. 
     
     
         18 . The binding agent of  claim 6 , which comprises a heavy chain variable region comprising SEQ ID NO:24 and a light chain variable region comprising SEQ ID NO:25. 
     
     
         19 . The binding agent of  claim 1 , which comprises a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region comprises heavy chain CDRs 1, 2, and 3 of an amino acid sequence set forth in SEQ ID NO:18, and the light chain variable region comprises light chain CDRs 1, 2, and 3 of an amino acid sequence set forth in SEQ ID NO:19. 
     
     
         20 . The binding agent of  claim 19 , wherein heavy chain CDR1 comprises GYTFTDFYMD (SEQ ID NO:7), heavy chain CDR2 comprises YIYPHNGGTTYNQNFTG (SEQ ID NO:8), heavy chain CDR3 comprises RGGFDFDY (SEQ ID NO:9), light chain CDR1 comprises KASENVDTYVS (SEQ ID NO:10), light chain CDR2 comprises GASNRYT (SEQ ID NO:11), and light chain CDR3 comprises GQSHSYPLT (SEQ ID NO:12). 
     
     
         21 . The binding agent of  claim 1 , which comprises a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region comprises heavy chain CDRs 1, 2, and 3 of an amino acid sequence set forth in SEQ ID NO:20, and the light chain variable region comprises light chain CDRs 1, 2, and 3 of an amino acid sequence set forth in SEQ ID NO:25. 
     
     
         22 . The binding agent of  claim 21 , which comprises a heavy chain variable region and a light chain variable region, wherein heavy chain CDR1 comprises GYTFTDFYMD (SEQ ID NO:7), heavy chain CDR2 comprises YIYPHNGGTTYNQQFTG (SEQ ID NO:13), heavy chain CDR3 comprises RGGFDFDY (SEQ ID NO:9), light chain CDR1 comprises KASENVDTYVS (SEQ ID NO:10), light chain CDR2 comprises GASNRYT (SEQ ID NO:11), and light chain CDR3 comprises GQSHSYPLT (SEQ ID NO:12). 
     
     
         23 . The binding agent of  claim 1 , which comprises a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region comprises heavy chain CDRs 1, 2, and 3 of an amino acid sequence set forth in SEQ ID NO:21, and the light chain variable region comprises light chain CDRs 1, 2, and 3 of an amino acid sequence set forth in SEQ ID NO:25. 
     
     
         24 . The binding agent of  claim 23 , wherein heavy chain CDR1 comprises GYTFTDFYMD (SEQ ID NO:7), heavy chain CDR2 comprises YIYPHNAGTTYNQQFTG (SEQ ID NO:14), heavy chain CDR3 comprises RGGFDFDY (SEQ ID NO:9), light chain CDR1 comprises KASENVDTYVS (SEQ ID NO:10), light chain CDR2 comprises GASNRYT (SEQ ID NO:11), and light chain CDR3 comprises GQSHSYPLT (SEQ ID NO:12). 
     
     
         25 . The binding agent of  claim 1 , which comprises a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region comprises heavy chain CDRs 1, 2, and 3 of an amino acid sequence set forth in SEQ ID NO:22, and the light chain variable region comprises light chain CDRs 1, 2, and 3 of an amino acid sequence set forth in SEQ ID NO:25. 
     
     
         26 . The binding agent of  claim 25 , wherein heavy chain CDR1 comprises GYTFTDFYMD (SEQ ID NO:7), heavy chain CDR2 comprises YIYPHNTGTTYNQQFTG (SEQ ID NO:15), heavy chain CDR3 comprises RGGFDFDY (SEQ ID NO:9), light chain CDR1 comprises KASENVDTYVS (SEQ ID NO:10), light chain CDR2 comprises GASNRYT (SEQ ID NO:11), and light chain CDR3 comprises GQSHSYPLT (SEQ ID NO:12). 
     
     
         27 . The binding agent of  claim 1 , which comprises a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region comprises heavy chain CDRs 1, 2, and 3 of an amino acid sequence set forth in SEQ ID NO:23, and the light chain variable region comprises light chain CDRs 1, 2, and 3 of an amino acid sequence set forth in SEQ ID NO:25. 
     
     
         28 . The binding agent of  claim 27 , wherein heavy chain CDR1 comprises GYTFTDFYMD (SEQ ID NO:7), heavy chain CDR2 comprises YIYPHEGGTTYNQQFTG (SEQ ID NO:16), heavy chain CDR3 comprises RGGFDFDY (SEQ ID NO:9), light chain CDR1 comprises KASENVDTYVS (SEQ ID NO:10), light chain CDR2 comprises GASNRYT (SEQ ID NO:11), and light chain CDR3 comprises GQSHSYPLT (SEQ ID NO:12). 
     
     
         29 . The binding agent of  claim 1 , which comprises a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region comprises heavy chain CDRs 1, 2, and 3 of an amino acid sequence set forth in SEQ ID NO:24, and the light chain variable region comprises light chain CDRs 1, 2, and 3 of an amino acid sequence set forth in SEQ ID NO:25. 
     
     
         30 . The binding agent of  claim 29 , wherein heavy chain CDR1 comprises GYTFTDFYMD (SEQ ID NO:7), heavy chain CDR2 comprises YIYPHQGGTTYNQQFTG (SEQ ID NO:17), heavy chain CDR3 comprises RGGFDFDY (SEQ ID NO:9), light chain CDR1 comprises KASENVDTYVS (SEQ ID NO:10), light chain CDR2 comprises GASNRYT (SEQ ID NO:11), and light chain CDR3 comprises GQSHSYPLT (SEQ ID NO:12). 
     
     
         31 . A binding agent that specifically binds human C3, which comprises a CDR1, CDR2, and CDR3 from a heavy chain variable region having the amino acid sequence of SEQ ID NO:18 and a CDR1, CDR2, and CDR3 from a light chain variable region having the amino acid sequence of SEQ ID NO:19. 
     
     
         32 . A binding agent that specifically binds human C3, which comprises a CDR1, CDR2, and CDR3 from a heavy chain variable region having the amino acid sequence of SEQ ID NO:20 and a CDR1, CDR2, and CDR3 from a light chain variable region having the amino acid sequence of SEQ ID NO:25. 
     
     
         33 . A binding agent that specifically binds human C3, which comprises a CDR1, CDR2, and CDR3 from a heavy chain variable region having the amino acid sequence of SEQ ID NO:21 and a CDR1, CDR2, and CDR3 from a light chain variable region having the amino acid sequence of SEQ ID NO:25. 
     
     
         34 . A binding agent that specifically binds human C3, which comprises a CDR1, CDR2, and CDR3 from a heavy chain variable region having the amino acid sequence of SEQ ID NO:22 and a CDR1, CDR2, and CDR3 from a light chain variable region having the amino acid sequence of SEQ ID NO:25. 
     
     
         35 . A binding agent that specifically binds human C3, which comprises a CDR1, CDR2, and CDR3 from a heavy chain variable region having the amino acid sequence of SEQ ID NO:23 and a CDR1, CDR2, and CDR3 from a light chain variable region having the amino acid sequence of SEQ ID NO:25. 
     
     
         36 . A binding agent that specifically binds human C3, which comprises a CDR1, CDR2, and CDR3 from a heavy chain variable region having the amino acid sequence of SEQ ID NO:24 and a CDR1, CDR2, and CDR3 from a light chain variable region having the amino acid sequence of SEQ ID NO:25. 
     
     
         37 . A binding agent that specifically binds human C3, which comprises a heavy chain comprising the amino acid sequence of SEQ ID NO:28 and a light chain comprising the amino acid sequence of SEQ ID NO:29. 
     
     
         38 . A binding agent that specifically binds human complement component C3 (C3), which comprises a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region comprises heavy chain CDRs 1, 2, and 3 of an amino acid sequence set forth in SEQ ID NO:91, and the light chain variable region comprises light chain CDRs 1, 2, and 3 of an amino acid sequence set forth in SEQ ID NO:92. 
     
     
         39 . The binding agent of  claim 38 , wherein heavy chain CDR1 comprises GYSFTGYNMN (SEQ ID NO:38), heavy chain CDR2 comprises NINPYYGSTNYNQKFKG (SEQ ID NO:39), heavy chain CDR3 comprises GYYGGNYPFAY (SEQ ID NO:40), light chain CDR1 comprises RASENIYSYLA (SEQ ID NO:41), light chain CDR2 comprises NAKTLAE (SEQ ID NO:42), and light chain CDR3 comprises QHYYGTPYT (SEQ ID NO:43). 
     
     
         40 . A binding agent that specifically binds human complement component C3 (C3), which comprises a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region comprises heavy chain CDRs 1, 2, and 3 of an amino acid sequence set forth in SEQ ID NO:93, and the light chain variable region comprises light chain CDRs 1, 2, and 3 of an amino acid sequence set forth in SEQ ID NO:94. 
     
     
         41 . The binding agent of  claim 40 , wherein heavy chain CDR1 comprises GYSFTGYNMN (SEQ ID NO:38), heavy chain CDR2 comprises NINPYYDSTSYNQKFKG (SEQ ID NO:44), heavy chain CDR3 comprises ENYDFVGFAY (SEQ ID NO:45), light chain CDR1 comprises RASSSVSYMH (SEQ ID NO:46), light chain CDR2 comprises VTSNLAS (SEQ ID NO:47), and light chain CDR3 comprises QQWSTNPLT (SEQ ID NO:48). 
     
     
         42 . A binding agent that specifically binds human complement component C3 (C3), which comprises a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region comprises heavy chain CDRs 1, 2, and 3 of an amino acid sequence set forth in SEQ ID NO:95, and the light chain variable region comprises light chain CDRs 1, 2, and 3 of an amino acid sequence set forth in SEQ ID NO:96. 
     
     
         43 . The binding agent of  claim 42 , wherein heavy chain CDR1 comprises GYSFTGYNMH (SEQ ID NO:49), heavy chain CDR2 comprises NINPYYGTTNSNQKFED (SEQ ID NO:50), heavy chain CDR3 comprises GIYYYGTGYPYFDF (SEQ ID NO:51), light chain CDR1 comprises RASQDINNYLN (SEQ ID NO:52), light chain CDR2 comprises YTSRLHS (SEQ ID NO:53), and light chain CDR3 comprises QQGITLPWT (SEQ ID NO:54). 
     
     
         44 . A binding agent that specifically binds human complement component C3 (C3), which comprises a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region comprises heavy chain CDRs 1, 2, and 3 of an amino acid sequence set forth in SEQ ID NO:97, and the light chain variable region comprises light chain CDRs 1, 2, and 3 of an amino acid sequence set forth in SEQ ID NO:98. 
     
     
         45 . The binding agent of  claim 44 , wherein heavy chain CDR1 comprises GYTFTDYWIN (SEQ ID NO:55), heavy chain CDR2 comprises NIYPGSTSANYNEKFKS (SEQ ID NO:56), heavy chain CDR3 comprises YGYDSWFAY (SEQ ID NO:57), light chain CDR1 comprises KSTKSLLNSDGFTYLD (SEQ ID NO:58), light chain CDR2 comprises LVSNRFS (SEQ ID NO:59), and light chain CDR3 comprises FQSNYLPLT (SEQ ID NO:60). 
     
     
         46 . A binding agent that specifically binds human complement component C3 (C3), which comprises a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region comprises heavy chain CDRs 1, 2, and 3 of an amino acid sequence set forth in SEQ ID NO:99, and the light chain variable region comprises light chain CDRs 1, 2, and 3 of an amino acid sequence set forth in SEQ ID NO:100. 
     
     
         47 . The binding agent of  claim 46 , wherein heavy chain CDR1 comprises GYAFNSCWMN (SEQ ID NO:61), heavy chain CDR2 comprises RIYPGDGDTNYNGKFKG (SEQ ID NO:62), heavy chain CDR3 comprises EGRNYGYEDY (SEQ ID NO:63), light chain CDR1 comprises KASQSVDYDGDSYMN (SEQ ID NO:64), light chain CDR2 comprises AASDLES (SEQ ID NO:65), and light chain CDR3 comprises QQANEDPRT (SEQ ID NO:66). 
     
     
         48 . A binding agent that specifically binds human complement component C3 (C3), which comprises a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region comprises heavy chain CDRs 1, 2, and 3 of an amino acid sequence set forth in SEQ ID NO:101, and the light chain variable region comprises light chain CDRs 1, 2, and 3 of an amino acid sequence set forth in SEQ ID NO:102. 
     
     
         49 . The binding agent of  claim 48 , wherein heavy chain CDR1 comprises GFTFSNYAMS (SEQ ID NO:67), heavy chain CDR2 comprises QTISSGGRYTYYPDSVKG (SEQ ID NO:68), heavy chain CDR3 comprises RYYGNSYWYFDV (SEQ ID NO:69), light chain CDR1 comprises KSSQSLLNSGNQKHYLT (SEQ ID NO:70), light chain CDR2 comprises GASTRGS (SEQ ID NO:71), and light chain CDR3 comprises QNDHSYPYT (SEQ ID NO:72). 
     
     
         50 . A binding agent that specifically binds human complement component C3 (C3), which comprises a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region comprises heavy chain CDRs 1, 2, and 3 of an amino acid sequence set forth in SEQ ID NO:103, and the light chain variable region comprises light chain CDRs 1, 2, and 3 of an amino acid sequence set forth in SEQ ID NO:104. 
     
     
         51 . The binding agent of  claim 50 , wherein heavy chain CDR1 comprises GFTFSSYTMS (SEQ ID NO:73), heavy chain CDR2 comprises YISSGGGTTYYPDTVKG (SEQ ID NO:74), heavy chain CDR3 comprises RYYRGSSLWYFDV (SEQ ID NO:75), light chain CDR1 comprises KSSQSLFNSGSQKNFLT (SEQ ID NO:76), light chain CDR2 comprises WASTRES (SEQ ID NO:77), and light chain CDR3 comprises QNDYSYPLT (SEQ ID NO:78). 
     
     
         52 . A binding agent that specifically binds human complement component C3 (C3), which comprises a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region comprises heavy chain CDRs 1, 2, and 3 of an amino acid sequence set forth in SEQ ID NO:105, and the light chain variable region comprises light chain CDRs 1, 2, and 3 of an amino acid sequence set forth in SEQ ID NO:106. 
     
     
         53 . The binding agent of  claim 52 , wherein heavy chain CDR1 comprises GYSITSGYSLH (SEQ ID NO:79), heavy chain CDR2 comprises YIHYSGSTNYNPSLKS (SEQ ID NO:80), heavy chain CDR3 comprises AWDYLDY (SEQ ID NO:81), light chain CDR1 comprises RASENIYSQLA (SEQ ID NO:82), light chain CDR2 comprises DAKTLAE (SEQ ID NO:83), and light chain CDR3 comprises HHHFGILYT (SEQ ID NO; 84). 
     
     
         54 . A binding agent that specifically binds human complement component C3 (C3), which comprises a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region comprises heavy chain CDRs 1, 2, and 3 of an amino acid sequence set forth in SEQ ID NO:107, and the light chain variable region comprises light chain CDRs 1, 2, and 3 of an amino acid sequence set forth in SEQ ID NO:108. 
     
     
         55 . The binding agent of  claim 54 , wherein heavy chain CDR1 comprises GYSITSGYYWN (SEQ ID NO:85), heavy chain CDR2 comprises YIRYDGSNNYNPSLKN (SEQ ID NO:86), heavy chain CDR3 comprises HYGYDGGAFDF (SEQ ID NO:87), light chain CDR1 comprises RTSENIYNYLV (SEQ ID NO:88), light chain CDR2 comprises NAKTLEE (SEQ ID NO:89), and light chain CDR3 comprises QHHYGTPFT (SEQ ID NO:90). 
     
     
         56 . The binding agent of any one of  claims 1 - 55 , which is an antibody. 
     
     
         57 . The binding agent of any one of  claims 1 - 56 , which is a monoclonal antibody. 
     
     
         58 . The binding agent of any one of  claims 1 - 57 , which is a chimeric, humanized, or human antibody. 
     
     
         59 . The binding agent of any one of  claims 1 - 58 , which is a bispecific antibody or a multispecific antibody. 
     
     
         60 . The binding agent of any one of  claims 56 - 59 , which is an antibody fragment comprising at least one antigen-binding site. 
     
     
         61 . The binding agent of  claim 56 , which is a Fab, Fab′, F(ab′) 2 , Fv, scFv, (scFv) 2 , single chain antibody, dual variable region antibody, diabody, nanobody, or single variable region antibody. 
     
     
         62 . The binding agent of  claim 56 , which is a disulfide-linked scFv (dsscFv) comprising a heavy chain variable region and a light chain variable region. 
     
     
         63 . The binding agent of  claim 62 , wherein the heavy chain variable region comprises an amino acid sequence set forth in SEQ ID NO:110 or SEQ ID NO:111, and the light chain variable region comprises an amino acid sequence set forth in SEQ ID NO:112. 
     
     
         64 . The binding agent of  claim 62 , wherein the dsscFv comprises an amino acid sequence of SEQ ID NO:113, SEQ ID NO: 114, SEQ ID NO:119, or SEQ ID NO:229. 
     
     
         65 . The binding agent of any one of  claims 60 - 64 , wherein the binding agent is attached to a half-life extending moiety. 
     
     
         66 . The binding agent of any one of  claims 56 - 59 , which is an IgG1 antibody. 
     
     
         67 . The binding agent of any one of  claims 56 - 59 , which is an IgG2 antibody. 
     
     
         68 . The binding agent of any one of  claims 56 - 59 , which is an IgG4 antibody. 
     
     
         69 . A binding agent that specifically binds human complement component C3 (C3; SEQ ID NO:1), wherein the binding agent comprises a scaffold protein and a heavy chain CDR1, CDR2, and CDR3 and light chain CDR1, CDR2, and CDR3 from:
 (i) a heavy chain variable region comprising SEQ ID NO:18 and a light chain variable region comprising SEQ ID NO:19;   (ii) a heavy chain variable region comprising SEQ ID NO:20 and a light chain variable region comprising SEQ ID NO:25;   (iii) a heavy chain variable region comprising SEQ ID NO:21 and a light chain variable region comprising SEQ ID NO:25; or   (iv) a heavy chain variable region comprising SEQ ID NO:22 and a light chain variable region comprising SEQ ID NO:25.   
     
     
         70 . The binding agent of any one of  claims 1 - 69 , which does not bind C3b at a detectable level. 
     
     
         71 . The binding agent of any one of  claims 1 - 69 , which binds C3 with an affinity that is at least 50-fold greater than the agent's affinity to C3b. 
     
     
         72 . The binding agent of any one of  claims 1 - 69 , which binds C3 with an affinity that is at least 100-fold greater than the agent's affinity to C3b. 
     
     
         73 . The binding agent of any one of  claims 1 - 69 , which is an antagonist of C3. 
     
     
         74 . The binding agent of any one of  claims 1 - 73 , which inhibits C3 activity. 
     
     
         75 . The binding agent of any one of  claims 1 - 74 , which inhibits complement activation. 
     
     
         76 . The binding agent of any one of  claims 1 - 75 , which inhibits activation of the classical complement pathway. 
     
     
         77 . The binding agent of any one of  claims 1 - 75 , which inhibits activation of the alternative complement pathway. 
     
     
         78 . The binding agent of any one of  claims 1 - 75 , which inhibits activation of the classical complement pathway and the alternative complement pathway. 
     
     
         79 . A binding agent that specifically binds human complement component C3 (C3; SEQ ID NO:1), which has at least one or more of the following properties:
 (a) binds to cyno C3 (e.g., SEQ ID NO:32);   (b) inhibits C3 cleavage,   (c) inhibits C3 cleavage and C3a release,   (d) inhibits activation of the alternative complement pathway (e.g., as assessed by hemolytic assays),   (e) inhibits activation of the classical complement pathway (e.g., as assessed by hemolytic assays),   (f) inhibits activation of the alternative complement pathway and classical complement pathway (e.g., as assessed by hemolytic assays),   (g) does not detectably bind to Factor Bb,   (h) does not detectably bind to C3d,   (i) does not detectably bind to C3a,   (j) does not detectably bind to C3b,   (k) does not detectably bind to iC3b,   (l) does not detectably bind to Factor Bb and C3d,   (m) does not detectably bind to Factor Bb, C3d, and C3a,   (n) does not detectably bind to Factor Bb, C3d, C3a, C3b, and iC3b,   (o) binds to human C3 with a greater affinity than compstatin, and   (p) has a half-life of about 4-5 days in human vitreous humor.   
     
     
         80 . The binding agent of  claim 79 , which comprises:
 (a) a heavy chain CDR1 comprising SEQ ID NO:7, a heavy chain CDR2 comprising SEQ ID NO:8, a heavy chain CDR3 comprising SEQ ID NO:9, a light chain CDR1 comprising SEQ ID NO:10, a light chain CDR2 comprising SEQ ID NO:11, and a light chain CDR3 comprising SEQ ID NO:12;   (b) a heavy chain CDR1 comprising SEQ ID NO:7, a heavy chain CDR2 comprising SEQ ID NO:13, a heavy chain CDR3 comprising SEQ ID NO:9, a light chain CDR1 comprising SEQ ID NO:10, a light chain CDR2 comprising SEQ ID NO:11, and a light chain CDR3 comprising SEQ ID NO:12;   (c) a heavy chain CDR1 comprising SEQ ID NO:7, a heavy chain CDR2 comprising SEQ ID NO:14, a heavy chain CDR3 comprising SEQ ID NO:9, a light chain CDR1 comprising SEQ ID NO:10, a light chain CDR2 comprising SEQ ID NO:11, and a light chain CDR3 comprising SEQ ID NO:12;   (d) a heavy chain CDR1 comprising SEQ ID NO:7, a heavy chain CDR2 comprising SEQ ID NO:15, a heavy chain CDR3 comprising SEQ ID NO:9, a light chain CDR1 comprising SEQ ID NO:10, a light chain CDR2 comprising SEQ ID NO:11, and a light chain CDR3 comprising SEQ ID NO:12;   (e) a heavy chain CDR1 comprising SEQ ID NO:7, a heavy chain CDR2 comprising SEQ ID NO:16, a heavy chain CDR3 comprising SEQ ID NO:9, a light chain CDR1 comprising SEQ ID NO:10, a light chain CDR2 comprising SEQ ID NO:11, and a light chain CDR3 comprising SEQ ID NO:12; or   (f) a heavy chain CDR1 comprising SEQ ID NO:7, a heavy chain CDR2 comprising SEQ ID NO:17, a heavy chain CDR3 comprising SEQ ID NO:9, a light chain CDR1 comprising SEQ ID NO:10, a light chain CDR2 comprising SEQ ID NO:11, and a light chain CDR3 comprising SEQ ID NO:12.   
     
     
         81 . The binding agent of  claim 79 , which comprises a heavy chain CDR1 comprising SEQ ID NO:7, a heavy chain CDR2 comprising SEQ ID NO: 14, a heavy chain CDR3 comprising SEQ ID NO:9, a light chain CDR1 comprising SEQ ID NO:10, a light chain CDR2 comprising SEQ ID NO:11, and a light chain CDR3 comprising SEQ ID NO:12. 
     
     
         82 . The binding agent of  claim 79 , which comprises:
 (a) a heavy chain variable region comprising SEQ ID NO:20 and a light chain variable region comprising SEQ ID NO:25;   (b) a heavy chain variable region comprising SEQ ID NO:21 and a light chain variable region comprising SEQ ID NO:25;   (c) a heavy chain variable region comprising SEQ ID NO:22 and a light chain variable region comprising SEQ ID NO:25;   (d) a heavy chain variable region comprising SEQ ID NO:23 and a light chain variable region comprising SEQ ID NO:25; or   (e) a heavy chain variable region comprising SEQ ID NO:24 and a light chain variable region comprising SEQ ID NO:25.   
     
     
         83 . The binding agent of  claim 79 , which comprises a heavy chain variable region comprising SEQ ID NO:21 and a light chain variable region comprising SEQ ID NO:25. 
     
     
         84 . The binding agent of any one of  claims 79 - 83 , which is an antibody. 
     
     
         85 . The binding agent of any one of  claims 79 - 84 , which is a monoclonal antibody. 
     
     
         86 . The binding agent of any one of  claims 79 - 85 , which is a chimeric, humanized, or human antibody. 
     
     
         87 . The binding agent of any one of  claims 79 - 86 , which is a bispecific antibody or a multispecific antibody. 
     
     
         88 . The binding agent of any one of  claims 79 - 87 , which is an antibody fragment comprising at least one antigen-binding site. 
     
     
         89 . The binding agent of  claim 84 , which is a Fab, Fab′, F(ab′)2, Fv, scFv, (scFv)2, single chain antibody, dual variable region antibody, diabody, nanobody, or single variable region antibody. 
     
     
         90 . The binding agent of  claim 84 , which is a disulfide-linked scFv (dsscFv). 
     
     
         91 . The binding agent of  claim 89  or  90 , wherein the binding agent is attached to a half-life extending moiety. 
     
     
         92 . The binding agent of any one of  claims 84 - 87 , which is an IgG1 antibody. 
     
     
         93 . The binding agent of any one of  claims 84 - 87 , which is an IgG2 antibody. 
     
     
         94 . The binding agent of any one of  claims 84 - 87 , which is an IgG4 antibody. 
     
     
         95 . A monoclonal antibody that specifically binds human complement component C3 (C3; SEQ ID NO:1), which comprises a heavy chain comprising the amino acid sequence of SEQ ID NO:28 and a light chain comprising the amino acid sequence of SEQ ID NO:29. 
     
     
         96 . An antibody that competes with the binding agent of any one of  claims 1 - 94  for binding to human C3. 
     
     
         97 . A pharmaceutical composition that comprises the binding agent of any one of  claims 1 - 94  and a pharmaceutically acceptable carrier. 
     
     
         98 . A pharmaceutical composition that comprises the monoclonal antibody of  claim 95  and a pharmaceutically acceptable carrier. 
     
     
         99 . An isolated polynucleotide or polynucleotides encoding the binding agent of any one of  claims 1 - 94 . 
     
     
         100 . An isolated polynucleotide or polynucleotides encoding the monoclonal antibody of  claim 95 . 
     
     
         101 . A vector or vectors comprising the polynucleotide or polynucleotides of  claim 99  or  claim 100 . 
     
     
         102 . An isolated cell comprising the polynucleotide or polynucleotides of  claim 99  or  claim 100 . 
     
     
         103 . An isolated cell comprising the vector or vectors of  claim 101 . 
     
     
         104 . An isolated cell producing the binding agent of any one of  claims 1 - 94  or the antibody of  claim 95 . 
     
     
         105 . A hybridoma that produces the monoclonal antibody of  claim 95 . 
     
     
         106 . A method of treating an eye disorder in a subject, the method comprising administering to the subject a therapeutically effective amount of the binding agent of any one of  claims 1 - 94  or the monoclonal antibody of  claim 95 . 
     
     
         107 . The method of  claim 106 , wherein the eye disorder is selected from the group consisting of: macular degeneration, diabetic retinopathy, retinopathy of prematurity, macular dystrophy, retinal dystrophy, uveitis, keratitis, scleritis, retinitis pigmentosa, choroidal neovascularization, retinal neovascularization, and ocular inflammation. 
     
     
         108 . A method of treating age-related macular degeneration (AMD) in a subject, the method comprising administering to the subject a therapeutically effective amount of the binding agent of any one of  claims 1 - 94  or the monoclonal antibody of  claim 95 . 
     
     
         109 . The method of  claim 108 , wherein the AMD is dry AMD. 
     
     
         110 . The method of  claim 108 , wherein the AMD is geographic atrophy. 
     
     
         111 . A method of inhibiting or suppressing drusen formation in an eye of a subject, the method comprising administering to an eye of the subject a therapeutically effective amount of the binding agent of any one of  claims 1 - 94  or the monoclonal antibody of  claim 95 . 
     
     
         112 . A method of inhibiting or suppressing retinal pigment epithelium atrophy in an eye of a subject, the method comprising administering to an eye of the subject a therapeutically effective amount of the binding agent of any one of  claims 1 - 94  or the monoclonal antibody of  claim 95 . 
     
     
         113 . A method of inhibiting complement activation in an eye of a subject, the method comprising administering to an eye of the subject a therapeutically effective amount of the binding agent of any one of  claims 1 - 94  or the monoclonal antibody of  claim 95 . 
     
     
         114 . The method of any one of  claims 106 - 113 , wherein the binding agent or antibody is administered to an eye of the subject by ocular injection, intraocular injection, or intravitreal injection. 
     
     
         115 . The method of any one of  claims 106 - 113 , wherein the binding agent or antibody is administered to an eye of the subject by intravitreal injection. 
     
     
         116 . The method of any one of  claims 106 - 113 , wherein the binding agent or antibody is administered as part of a combination therapy. 
     
     
         117 . The method of  claim 116 , wherein the combination therapy comprises photodynamic therapy. 
     
     
         118 . The method of  claim 116 , wherein the combination therapy comprises at least one additional therapeutic agent. 
     
     
         119 . The method of  claim 118 , wherein the additional therapeutic agent is selected from the group consisting of: a VEGF inhibitor, a complement inhibitor, a PDGF inhibitor, and a steroid. 
     
     
         120 . The method of  claim 118 , wherein the additional therapeutic agent is a VEGF inhibitor. 
     
     
         121 . The method of  claim 120 , wherein the VEGF inhibitor is selected from the group consisting of: pegaptanib, ranibizumab, bevacizumab, aflibercept, and OPT-302. 
     
     
         122 . The method of any one of  claims 106 - 121 , wherein the subject is a human. 
     
     
         123 . Use of the binding agent of any one of  claims 1 - 94  in the manufacture of a medicament for treatment of an eye disorder. 
     
     
         124 . The use of  claim 123 , wherein the eye disorder is selected from the group consisting of: macular degeneration, diabetic retinopathy, retinopathy of prematurity, macular dystrophy, retinal dystrophy, uveitis, keratitis, scleritis, retinitis pigmentosa, choroidal neovascularization, retinal neovascularization, and ocular inflammation. 
     
     
         125 . The use of  claim 123 , wherein the eye disorder is aged-related macular degeneration (AMD). 
     
     
         126 . The use of  claim 125 , wherein the AMD is dry AMD. 
     
     
         127 . The use of  claim 125 , wherein the AMD is geographic atrophy. 
     
     
         128 . Use of the monoclonal antibody of  claim 95  in the manufacture of a medicament for treatment of an eye disorder. 
     
     
         129 . The use of  claim 128 , wherein the eye disorder is selected from the group consisting of: macular degeneration, diabetic retinopathy, retinopathy of prematurity, macular dystrophy, retinal dystrophy, uveitis, keratitis, scleritis, retinitis pigmentosa, choroidal neovascularization, retinal neovascularization, and ocular inflammation. 
     
     
         130 . The use of  claim 128 , wherein the eye disorder is aged-related macular degeneration (AMD). 
     
     
         131 . The use of  claim 130 , wherein the AMD is dry AMD. 
     
     
         132 . The use of  claim 130 , wherein the AMD is geographic atrophy. 
     
     
         133 . A method of making the binding agent of any one of  claims 1 - 94  or the antibody of  claim 95 , comprising: (a) culturing the cell of any one of  claim 102 - 104 , and (b) isolating the binding agent or antibody. 
     
     
         134 . The method of  claim 133 , further comprising formulating the binding agent or antibody as a pharmaceutical composition.

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