Composition and method for the diagnosis and treatment of diseases associated with neurite degeneration

Abstract

Provided herein are antibodies and methods of using the antibodies to treat and diagnose neurite degenerative diseases and disorders.

1 . An isolated antibody or antibody fragment thereof which binds to Repulsive Guidance Molecule a (“RGMa”), wherein the antibody comprises a domain or region selected from the group consisting of: (a) a variable heavy domain region comprising the amino acid sequence of SEQ ID NO:1, (b) a variable light domain region comprising the amino acid sequence of SEQ ID NO:5, (c) a variable heavy domain region comprising the amino acid sequence of SEQ ID NO:9, (d) a variable light domain region comprising the amino acid sequence of SEQ ID NO:13, (e) a variable heavy domain region comprising the amino acid sequence of SEQ ID NO:17, (f) a variable light domain region comprising the amino acid sequence of SEQ ID NO:21, (g) a variable heavy domain region comprising the amino acid sequence of SEQ ID NO:25, (h) a variable light domain region comprising the amino acid sequence of SEQ ID NO:29, (i) a variable heavy domain region comprising the amino acid sequence of SEQ ID NO:33, (j) a variable light domain region comprising the amino acid sequence of SEQ ID NO:37; (k) a variable heavy domain region comprising the amino acid sequence of SEQ ID NO:41; (l) a variable light domain region comprising the amino acid sequence of SEQ ID NO:45; (m) a variable heavy domain region comprising the amino acid sequence of SEQ ID NO:49; (n) a variable light domain region comprising the amino acid sequence of SEQ ID NO:53, (o) a variable heavy domain region comprising the amino acid sequence of SEQ ID NO:57, (p) a variable light domain region comprising the amino acid sequence of SEQ ID NO:61, (q) a variable heavy domain region comprising the amino acid sequence of SEQ ID NO:152, (r) a variable light domain region comprising the amino acid sequence of SEQ ID NO:95, (s) a variable heavy domain region comprising the amino acid sequence of SEQ ID NO:99, (t) a variable light domain region comprising the amino acid sequence of SEQ ID NO:103, (u) a variable heavy domain region comprising the amino acid sequence of SEQ ID NO:107, (v) a variable light domain region comprising the amino acid sequence of SEQ ID NO:111, (w) a variable heavy domain region comprising the amino acid sequence of SEQ ID NO:115, (x) a variable light domain region comprising the amino acid sequence of SEQ ID NO:119, (y) a variable heavy domain region comprising the amino acid sequence of SEQ ID NO:123, (z) a variable light domain region comprising the amino acid sequence of SEQ ID NO:127, (aa) a variable heavy domain region comprising the amino acid sequence of SEQ ID NO:131, (bb) a variable light domain region comprising the amino acid sequence of SEQ ID NO:135, (cc) a variable light domain region comprising the amino acid sequence of SEQ ID NO:67, (dd) a variable light domain region comprising the amino acid sequence of SEQ ID NO:68, (ee) a variable light domain region comprising the amino acid sequence of SEQ ID NO:69 (ff) a variable light domain region comprising the amino acid sequence of SEQ ID NO:70, (gg) a variable light domain region comprising the amino acid sequence of SEQ ID NO:71, (hh) a variable light domain region comprising the amino acid sequence of SEQ ID NO:72, (ii) a variable light domain region comprising the amino acid sequence of SEQ ID NO:73, (jj) a variable heavy domain comprising the amino acid sequence of SEQ ID NO:1 and a variable light domain region comprising the amino acid sequence of SEQ ID NO:5, (kk) a variable heavy domain comprising the amino acid sequence of SEQ ID NO:9 and a variable light domain region comprising the amino acid sequence of SEQ ID NO:13, (ll) a variable heavy domain comprising the amino acid sequence of SEQ ID NO:17 and a variable light domain region comprising the amino acid sequence of SEQ ID NO:21, (mm) a variable heavy domain comprising the amino acid sequence of SEQ ID NO:25 and a variable light domain region comprising the amino acid sequence of SEQ ID NO:29, (nn) a variable heavy domain comprising the amino acid sequence of SEQ ID NO:33 and a variable light domain region comprising the amino acid sequence of SEQ ID NO:37, (oo) a variably heavy domain comprising the amino acid sequence of SEQ ID NO:41 and a variable light domain region comprising the amino acid sequence of SEQ ID NO:45, (pp) a variable heavy domain comprising the amino acid sequence of SEQ ID NO:49 and a variable light domain region comprising the amino acid sequence of SEQ ID NO:53, (qq) a variable heavy domain comprising the amino acid sequence of SEQ ID NO:57 and a variable light domain region comprising the amino acid sequence of SEQ ID NO:61, (rr) a variable heavy domain region comprising the amino acid sequence of SEQ ID NO:152 and a variable light domain region comprising the amino acid sequence of SEQ ID NO:95, (ss) a variable heavy domain region comprising the amino acid sequence of SEQ ID NO:99 and a variable light domain region comprising the amino acid sequence of SEQ ID NO:103, (tt) a variable heavy domain region comprising the amino acid sequence of SEQ ID NO:107 and a variable light domain region comprising the amino acid sequence of SEQ ID NO:111, (uu) a variable heavy domain region comprising the amino acid sequence of SEQ ID NO:115 and a variable light domain region comprising the amino acid sequence of SEQ ID NO:119, (vv) a variable heavy domain region comprising the amino acid sequence of SEQ ID NO:123 and a variable light domain region comprising the amino acid sequence of SEQ ID NO:127, (ww) a variable heavy domain region comprising the amino acid sequence of SEQ ID NO:131 and a variable light domain region comprising the amino acid sequence of SEQ ID NO:135, (xx) a variable heavy chain comprising a complementarity determining region (CDR)1 comprising the amino acid sequence of SEQ ID NO:2, a CDR2 comprising the amino acid sequence of SEQ ID NO:3, and a CDR3 comprising the amino acid sequence of SEQ ID NO:4, (yy) a variable light chain comprising a CDR1 comprising the amino acid sequence of SEQ ID NO:6, a CDR2 comprising the amino acid sequence of SEQ ID NO:7, and a CDR3 comprising the amino acid sequence of SEQ ID NO:8, (zz) a variable heavy chain comprising a CDR1 comprising the amino acid sequence of SEQ ID NO:10, a CDR2 comprising the amino acid sequence of SEQ ID NO:11, and a CDR3 comprising the amino acid sequence of SEQ ID NO:12, (aaa) a variable light chain comprising a CDR1 comprising the amino acid sequence of SEQ ID NO:14, a CDR2 comprising the amino acid sequence of SEQ ID NO:15, and a CDR3 comprising the amino acid sequence of SEQ ID NO:16, (bbb) a variable heavy chain comprising a CDR1 comprising the amino acid sequence of SEQ ID NO:18, a CDR2 comprising the amino acid sequence of SEQ ID NO:19, and a CDR3 comprising the amino acid sequence of SEQ ID NO:20, (ccc) a variable light chain comprising a CDR1 comprising the amino acid sequence of SEQ ID NO:22, a CDR2 comprising the amino acid sequence of SEQ ID NO:23, and a CDR3 comprising the amino acid sequence of SEQ ID NO:24, (ddd) a variable heavy chain comprising a CDR1 comprising the amino acid sequence of SEQ ID NO:26, a CDR2 comprising the amino acid sequence of SEQ ID NO:27, and a CDR3 comprising the amino acid sequence of SEQ ID NO:28, (eee) a variable light chain comprising a CDR1 comprising the amino acid sequence of SEQ ID NO:30, a CDR2 comprising the amino acid sequence of SEQ ID NO:31, and a CDR3 comprising the amino acid sequence of SEQ ID NO:32, (fff) a variable heavy chain comprising a CDR1 comprising the amino acid sequence of SEQ ID NO:34, a CDR2 comprising the amino acid sequence of SEQ ID NO:35, and a CDR3 comprising the amino acid sequence of SEQ ID NO:36, (ggg) a variable light chain comprising a CDR1 comprising the amino acid sequence of SEQ ID NO:38, a CDR2 comprising the amino acid sequence of SEQ ID NO:39, and a CDR3 comprising the amino acid sequence of SEQ ID NO:40, (hhh) a variable heavy chain comprising a CDR1 comprising the amino acid sequence of SEQ ID NO:42, a CDR2 comprising the amino acid sequence of SEQ ID NO:43, and CDR3 comprising the amino acid sequence of SEQ ID NO:44; (iii) a variable light chain comprising a CDR1 comprising the amino acid sequence of SEQ ID NO:46, a CDR2 comprising the amino acid sequence of SEQ ID NO:47, and a CDR3 comprising the amino acid sequence of SEQ ID NO:48; (jjj) a variable heavy chain comprising a CDR1 comprising the amino acid sequence of SEQ ID NO:50, a CDR2 comprising the amino acid sequence of SEQ ID NO:51, and a CDR3 comprising the amino acid sequence of SEQ ID NO:52 and a variable light chain comprising a CDR1 comprising the amino acid sequence of SEQ ID NO:54, a CDR2 comprising the amino acid sequence of SEQ ID NO:55, and a CDR3 comprising the amino acid sequence of SEQ ID NO:56, (kick) a variable heavy chain comprising a CDR1 comprising the amino acid sequence of SEQ ID NO:58, a CDR2 comprising the amino acid sequence of SEQ ID NO:59, and a CDR3 comprising the amino acid sequence of SEQ ID NO:60, (lll) a variable light chain comprising a
 CDR1 comprising the amino acid sequence of SEQ ID NO:62, a CDR2 comprising the amino acid sequence of SEQ ID NO:63, and a CDR3 comprising the amino acid sequence of SEQ ID NO:64, (mmm) a variable heavy chain comprising a CDR1 comprising the amino acid sequence of SEQ ID NO:92 or 153, a CDR2 comprising the amino acid sequence of SEQ ID NO:93 or 154, and a CDR3 comprising the amino acid sequence of SEQ ID NO:94 or 155, (nnn) a variable light chain comprising a CDR1 comprising the amino acid sequence of SEQ ID NO:96 or 156, a CDR2 comprising the amino acid sequence of SEQ ID NO:97 or 157, and a CDR3 comprising the amino acid sequence of SEQ ID NO:98 or 158, (000) a variable heavy chain comprising a CDR1 comprising the amino acid sequence of SEQ ID NO:100, a CDR2 comprising the amino acid sequence of SEQ ID NO:101, and a CDR3 comprising the amino acid sequence of SEQ ID NO:102, (ppp) a variable light chain comprising a CDR1 comprising the amino acid sequence of SEQ ID NO:104, a CDR2 comprising the amino acid sequence of SEQ ID NO:105, and a CDR3 comprising the amino acid sequence of SEQ ID NO:106, (qqq) a variable heavy chain comprising a CDR1 comprising the amino acid sequence of SEQ ID NO:108, a CDR2 comprising the amino acid sequence of SEQ ID NO:109, and a CDR3 comprising the amino acid sequence of SEQ ID NO:110, (rrr) a variable light chain comprising a CDR1 comprising the amino acid sequence of SEQ ID NO:112, a CDR2 comprising the amino acid sequence of SEQ ID NO:113, and a CDR3 comprising the amino acid sequence of SEQ ID NO:114, (sss) a variable heavy chain comprising a CDR1 comprising the amino acid sequence of SEQ ID NO:116, a CDR2 comprising the amino acid sequence of SEQ ID NO:117, and a CDR3 comprising the amino acid sequence of SEQ ID NO:118, (ttt) a variable light chain comprising a CDR1 comprising the amino acid sequence of SEQ ID NO:120, a CDR2 comprising the amino acid sequence of SEQ ID NO:121, and a CDR3 comprising the amino acid sequence of SEQ ID NO:122, (uuu) a variable heavy chain comprising a CDR1 comprising the amino acid sequence of SEQ ID NO:124, a CDR2 comprising the amino acid sequence of SEQ ID NO:125, and a CDR3 comprising the amino acid sequence of SEQ ID NO:126, (vvv) a variable light chain comprising a CDR1 comprising the amino acid sequence of SEQ ID NO:128, a CDR2 comprising the amino acid sequence of SEQ ID NO:129, and a CDR3 comprising the amino acid sequence of SEQ ID NO:130, (www) a variable heavy chain comprising a CDR1 comprising the amino acid sequence of SEQ ID NO:132, a CDR2 comprising the amino acid sequence of SEQ ID NO:133, and a CDR3 comprising the amino acid sequence of SEQ ID NO:134, (xxx) a variable light chain comprising a CDR1 comprising the amino acid sequence of SEQ ID NO:136, a CDR2 comprising the amino acid sequence of SEQ ID NO:137, and a CDR3 comprising the amino acid sequence of SEQ ID NO:138, (yyy) a variable light chain comprising a CDR1 comprising the amino acid sequence of SEQ ID NO:6, a CDR2 comprising the amino acid sequence of SEQ ID NO:7, and a CDR3 comprising the amino acid sequence of SEQ ID NO:67, (zzz) a variable light chain comprising a CDR1 comprising the amino acid sequence of SEQ ID NO:6, a CDR2 comprising the amino acid sequence of SEQ ID NO:7, and a CDR3 comprising the amino acid sequence of SEQ ID NO:68, (aaaa) a variable light chain comprising a CDR1 comprising the amino acid sequence of SEQ ID NO:6, a CDR2 comprising the amino acid sequence of SEQ ID NO:7, and a CDR3 comprising the amino acid sequence of SEQ ID NO:69, (bbbb) a variable light chain comprising a CDR1 comprising the amino acid sequence of SEQ ID NO:6, a CDR2 comprising the amino acid sequence of SEQ ID NO:7, and a CDR3 comprising the amino acid sequence of SEQ ID NO:70, (cccc) a variable light chain comprising a CDR1 comprising the amino acid sequence of SEQ ID NO:6, a CDR2 comprising the amino acid sequence of SEQ ID NO:7, and a CDR3 comprising the amino acid sequence of SEQ ID NO:71, (dddd) a variable light chain comprising a CDR1 comprising the amino acid sequence of SEQ ID NO:6, a CDR2 comprising the amino acid sequence of SEQ ID NO:7, and a CDR3 comprising the amino acid sequence of SEQ ID NO:72, (eeee) a variable light chain comprising a CDR1 comprising the amino acid sequence of SEQ ID NO:6, a CDR2 comprising the amino acid sequence of SEQ ID NO:7, and a CDR3 comprising the amino acid sequence of SEQ ID NO:73, (ffff) a variable heavy chain comprising a CDR1 comprising the amino acid sequence of SEQ ID NO:2, a CDR2 comprising the amino acid sequence of SEQ ID NO:3, and a CDR3 comprising the amino acid sequence of SEQ ID NO:4 and a variable light chain comprising a CDR1 comprising the amino acid sequence of SEQ ID NO:6, a CDR2 comprising the amino acid sequence of SEQ ID NO:7, and a CDR3 comprising the amino acid sequence of SEQ ID NO:8, (gggg) a variable heavy chain comprising a CDR1 comprising the amino acid sequence of SEQ ID NO:2, a CDR2 comprising the amino acid sequence of SEQ ID NO:3, and a CDR3 
 comprising the amino acid sequence of SEQ ID NO:4 and a variable light chain comprising a CDR1 comprising the amino acid sequence of SEQ ID NO:6, a CDR2 comprising the amino acid sequence of SEQ ID NO:7, and a CDR3 comprising the amino acid sequence of SEQ ID NO:67, (hhhh) a variable heavy chain comprising a CDR1 comprising the amino acid sequence of SEQ ID NO:92 or 153, a CDR2 comprising the amino acid sequence of SEQ ID NO:93 or 154, and a CDR3 comprising the amino acid sequence of SEQ ID NO:94 or 155 and a variable light chain comprising a CDR1 comprising the amino acid sequence of SEQ ID NO:96 or 156, a CDR2 comprising the amino acid sequence of SEQ ID NO:97 or 157, and a CDR3 comprising the amino acid sequence of SEQ ID NO:98 or 158, (iiii) a variable heavy chain comprising a CDR1 comprising the amino acid sequence of SEQ ID NO:100, a CDR2 comprising the amino acid sequence of SEQ ID NO:101, and a CDR3 comprising the amino acid sequence of SEQ ID NO:102 and a variable light chain comprising a CDR1 comprising the amino acid sequence of SEQ ID NO:104, a CDR2 comprising the amino acid sequence of SEQ ID NO:105, and a CDR3 comprising the amino acid sequence of SEQ ID NO:106, (jjjj) a variable heavy chain comprising a CDR1 comprising the amino acid sequence of SEQ ID NO:108, a CDR2 comprising the amino acid sequence of SEQ ID NO:109, and a CDR3 comprising the amino acid sequence of SEQ ID NO:110 and a variable light chain comprising a CDR1 comprising the amino acid sequence of SEQ ID NO:112, a CDR2 comprising the amino acid sequence of SEQ ID NO:113, and a CDR3 comprising the amino acid sequence of SEQ ID NO:114, (kkkk) a variable heavy chain comprising a CDR1 comprising the amino acid sequence of SEQ ID NO:116, a CDR2 comprising the amino acid sequence of SEQ ID NO:117, and a CDR3 comprising the amino acid sequence of SEQ ID NO:118 and a variable light chain comprising a CDR1 comprising the amino acid sequence of SEQ ID NO:120, a CDR2 comprising the amino acid sequence of SEQ ID NO:121, and a CDR3 comprising the amino acid sequence of SEQ ID NO:122, (llll) a variable heavy chain comprising a CDR1 comprising the amino acid sequence of SEQ ID NO:124, a CDR2 comprising the amino acid sequence of SEQ ID NO:125, and a CDR3 comprising the amino acid sequence of SEQ ID NO:126 and a variable light chain comprising a CDR1 comprising the amino acid sequence of SEQ ID NO:128, a CDR2 comprising the amino acid sequence of SEQ ID NO:129, and a CDR3 comprising the amino acid sequence of SEQ ID NO:130, (mmmm) a variable heavy chain comprising a CDR1 comprising the amino acid sequence of SEQ ID NO:132, a CDR2 comprising the amino acid sequence of SEQ ID NO:133, and a CDR3 comprising the amino acid sequence of SEQ ID NO:134 and a variable light chain comprising a CDR1 comprising the amino acid sequence of SEQ ID NO:136, a CDR2 comprising the amino acid sequence of SEQ ID NO:137, and a CDR3 comprising the amino acid sequence of SEQ ID NO:138, (nnnn) a variable heavy chain comprising a CDR1 comprising the amino acid sequence of SEQ ID NO:2, a CDR2 comprising the amino acid sequence of SEQ ID NO:3, and a CDR3 comprising the amino acid sequence of SEQ ID NO:4 and a variable light chain comprising a CDR1 comprising the amino acid sequence of SEQ ID NO:6, a CDR2 comprising the amino acid sequence of SEQ ID NO:7, and a CDR3 comprising the amino acid sequence of SEQ ID NO:68, (0000) a variable heavy chain comprising a CDR 1 comprising the amino acid sequence of SEQ ID NO:2, a CDR2 comprising the amino acid sequence of SEQ ID NO:3, and a CDR3 comprising the amino acid sequence of SEQ ID NO:4, and a variable light chain comprising a CDR1 comprising the amino acid sequence of SEQ ID NO:6, a CDR2 comprising the amino acid sequence of SEQ ID NO:7, and a CDR3 comprising the amino acid sequence of SEQ ID NO:69, (pppp) a variable heavy chain comprising a CDR 1 comprising the amino acid sequence of SEQ ID NO:2, a CDR2 comprising the amino acid sequence of SEQ ID NO:3, and a CDR3 comprising the amino acid sequence of SEQ ID NO:4, and a variable light chain comprising a CDR1 comprising the amino acid sequence of SEQ ID NO:6, a CDR2 comprising the amino acid sequence of SEQ ID NO:7, and a CDR3 comprising the amino acid sequence of SEQ ID NO:70, (qqqq) a variable heavy chain comprising a CDR 1 comprising the amino acid sequence of SEQ ID NO:2, a CDR2 comprising the amino acid sequence of SEQ ID NO:3, and a CDR3 comprising the amino acid sequence of SEQ ID NO:4, and a variable light chain comprising a CDR1 comprising the amino acid sequence of SEQ ID NO:6, a CDR2 comprising the amino acid sequence of SEQ ID NO:7, and a CDR3 comprising the amino acid sequence of SEQ ID NO:71, (rrrr) a variable heavy chain comprising a CDR 1 comprising the amino acid sequence of SEQ ID NO:2, a CDR2 comprising the amino acid sequence of SEQ ID NO:3, and a CDR3 comprising the amino acid sequence of SEQ ID NO:4, and a variable light chain comprising a CDR1 comprising the amino acid sequence of SEQ ID NO:6, a CDR2 comprising the amino acid sequence of SEQ ID NO:7, and a CDR3 comprising the amino acid sequence of SEQ ID NO:72, (ssss) a variable heavy chain comprising a CDR 1 comprising the amino acid sequence of SEQ ID NO:2, a CDR2 comprising the amino acid sequence of SEQ ID NO:3, and a CDR3 comprising the amino acid sequence of SEQ ID NO:4, and a variable light chain comprising a CDR1 comprising the amino acid sequence of SEQ ID NO:6, a CDR2 comprising the amino acid sequence of SEQ ID NO:7, and a CDR3 comprising the amino acid sequence of SEQ ID NO:73, (tttt) a variable heavy chain comprising a CDR 1 comprising the amino acid sequence of SEQ ID NO:10, a CDR2 comprising the amino acid sequence of SEQ ID NO:11, and a CDR3 comprising the amino acid sequence of SEQ ID NO:12, and a variable light chain comprising a CDR1 comprising the amino acid sequence of SEQ ID NO:14, a CDR2 comprising the amino acid sequence of SEQ ID NO:15, and a CDR3 comprising the amino acid sequence of SEQ ID NO:16, (uuuu) a variable heavy chain comprising a CDR 1 comprising the amino acid sequence of SEQ ID NO:18, a CDR2 comprising the amino acid sequence of SEQ ID NO:19, and a CDR3 comprising the amino acid sequence of SEQ ID NO:20, and a variable light chain comprising a CDR1 comprising the amino acid sequence of SEQ ID NO:22, a CDR2 comprising the amino acid sequence of SEQ ID NO:23, and a CDR3 comprising the amino acid sequence of SEQ ID NO:24, (vvvv) a variable heavy chain comprising a CDR 1 comprising the amino acid sequence of SEQ ID NO:26, a CDR2 comprising the amino acid sequence of SEQ ID NO:27, and a CDR3 comprising the amino acid sequence of SEQ ID NO:28, and a variable light chain comprising a CDR1 comprising the amino acid sequence of SEQ ID NO:30, a CDR2 comprising the amino acid sequence of SEQ ID NO:31, and a CDR3 comprising the amino acid sequence of SEQ ID NO:32, (wwww) a variable heavy chain comprising a CDR 1 comprising the amino acid sequence of SEQ ID NO:34, a CDR2 comprising the amino acid sequence of SEQ ID NO:35, and a CDR3 comprising the amino acid sequence of SEQ ID NO:36, and a variable light chain comprising a CDR1 comprising the amino acid sequence of SEQ ID NO:38, a CDR2 comprising the amino acid sequence of SEQ ID NO:39, and a CDR3 comprising the amino acid sequence of SEQ ID NO:40, (xxxx) a variable heavy domain chain comprising a CDR1 comprising the amino acid sequence of SEQ ID NO:42, a CDR2 comprising the amino acid sequence of SEQ ID NO:43, and a CDR comprising the amino acid sequence of SEQ ID NO:44, and a variable light domain chain comprising a CDR1 comprising the amino acid sequence of SEQ ID NO:46, a CDR2 comprising the amino acid sequence of SEQ ID NO:47, and a CDR3 comprising the amino acid sequence of SEQ ID NO:48; (yyyy) a variable heavy chain comprising a CDR 1 comprising the amino acid sequence of SEQ ID NO:50, a CDR2 comprising the amino acid sequence of SEQ ID NO:51, and a CDR3 comprising the amino acid sequence of SEQ ID NO:52, and a variable light chain comprising a CDR1 comprising the amino acid sequence of SEQ ID NO:54, a CDR2 comprising the amino acid sequence of SEQ ID NO:55, and a CDR3 comprising the amino acid sequence of SEQ ID NO:56, (zzzz) a variable heavy chain comprising a CDR 1 comprising the amino acid sequence of SEQ ID NO:58, a CDR2 comprising the amino acid sequence of SEQ ID NO:59, and a CDR3 comprising the amino acid sequence of SEQ ID NO:60, and a variable light chain comprising a CDR1 comprising the amino acid sequence of SEQ ID NO:62, a CDR2 comprising the amino acid sequence of SEQ ID NO:63, and a CDR3 comprising the amino acid sequence of SEQ ID NO:64. 
 
     
     
         2 . The isolated antibody or antibody fragment of  claim 1 , wherein the antibody is selected from the group consisting of a human antibody, an immunoglobulin molecule, a disulfide linked Fv, a monoclonal antibody, an affinity matured, a scFv, a chimeric antibody, a single domain antibody, a CDR-grafted antibody, a diabody, a humanized antibody, a multispecific antibody, a Fab, a dual specific antibody, a DVD, a Fab′, a bispecific antibody, a F(ab′)2, and a Fv. 
     
     
         3 . The isolated antibody or antibody fragment of  claim 3 , wherein the antibody or antibody fragment is human. 
     
     
         4 . The isolated antibody or antibody fragment of  claim 1 , wherein the monoclonal antibody or antibody fragment comprises a heavy chain immunoglobulin constant domain selected from the group consisting of a human IgM constant domain, a human IgG4 constant domain, a human IgG1 constant domain, a human IgE constant domain, a human IgG2 constant domain, a human igG3 constant domain, and a human IgA constant domain. 
     
     
         5 . The isolated antibody or antibody fragment of  claim 4 , wherein the human IgG1 constant domain comprises SEQ ID NO:140. 
     
     
         6 . The isolated antibody or antibody fragment of  claim 4 , wherein the human IgG1 constant domain consists of SEQ ID NO:140. 
     
     
         7 . The isolated antibody or antibody fragment of  claim 1 , wherein the antibody or antibody fragment comprises a variable heavy region comprising a sequence selected from the group consisting of SEQ ID NO:1, SEQ ID NO:9, SEQ ID NO:17, SEQ ID NO:25, SEQ ID NO:33, SEQ ID NO:41, SEQ ID NO:49, SEQ ID NO:57, SEQ ID NO:91, SEQ ID NO:99, SEQ ID NO:107, SEQ ID NO:115, SEQ ID NO:123, and SEQ ID NO:131. 
     
     
         8 . The isolated antibody or antibody fragment of  claim 1 , wherein the antibody or antibody fragment comprises a variable light region comprising a sequence selected from the group consisting of SEQ ID NO:5, SEQ ID NO:13, SEQ ID NO:21, SEQ ID NO:29, SEQ ID NO:37, SEQ ID NO:45, SEQ ID NO:53, SEQ ID NO:61, SEQ ID NO:95, SEQ ID NO:103, SEQ ID NO:111, SEQ ID NO:119, SEQ ID NO:127, and SEQ ID NO:135. 
     
     
         9 . The isolated antibody or antibody fragment of  claim 1 , wherein the antibody or antibody fragment comprises a variable light domain that comprises complementarity-determining region (CDR) residues SEQ ID NO:6, SEQ ID NO:7, and SEQ ID NO:8, or SEQ ID NO:6, SEQ ID NO:7, and SEQ ID NO:67, SEQ ID NO:6, SEQ ID NO:7, and SEQ ID NO:68, or SEQ ID NO:6, SEQ ID NO:7, and SEQ ID NO:69, or SEQ ID NO:6, SEQ ID NO:7, and SEQ ID NO:70, or SEQ ID NO:6, SEQ ID NO:7, and SEQ ID NO:71, or SEQ ID NO:6, SEQ ID NO:7, and SEQ ID NO:72 or SEQ ID NO:6, SEQ ID NO:7, and SEQ ID NO:73, or SEQ ID NO:14, SEQ ID NO:15, and SEQ ID NO:16, or SEQ ID NO:22, SEQ ID NO:23, and SEQ ID NO:24, or SEQ ID NO:30, SEQ ID NO:31, and SEQ ID NO:32, or SEQ ID NO:38, SEQ ID NO:39, and SEQ ID NO:40, or SEQ ID NO:54, SEQ ID NO:55, and SEQ ID NO:56, or SEQ ID NO:62, SEQ ID NO:63, and SEQ ID NO:64, or SEQ ID NO:46, SEQ ID NO:47, and SEQ ID NO:48, SEQ ID NO:96, SEQ ID NO:97, and SEQ ID NO:98, SEQ ID NO:104, SEQ ID NO:105, and SEQ ID NO:106, SEQ ID NO:112, SEQ ID NO:113, and SEQ ID NO:114, SEQ ID NO:120, SEQ ID NO:121, and SEQ ID NO:122, SEQ ID NO:128, SEQ ID NO:129, and SEQ ID NO:130, SEQ ID NO:136, SEQ ID NO:137, and SEQ ID NO:138, and SEQ ID NO: 156, and SEQ ID NO: 157, and SEQ ID NO: 158. 
     
     
         10 . The isolated antibody or antibody fragment of  claim 1 , wherein the antibody or antibody fragment comprises a variable heavy domain that comprises complementarity-determining region (CDR) residues SEQ ID NO:2, SEQ ID NO:3, and SEQ ID NO:4, or SEQ ID NO:10, SEQ ID NO:11, and SEQ ID NO:12, or SEQ ID NO:18, SEQ ID NO:19, and SEQ ID NO:20, or SEQ ID NO:26, SEQ ID NO:27, and SEQ ID NO:28, or SEQ ID NO:34, SEQ ID NO:35, and SEQ ID NO:36, or SEQ ID NO:50, SEQ ID NO:51, and SEQ ID NO:52, or SEQ ID NO:58, SEQ ID NO:59, and SEQ ID NO:60, SEQ ID NO:42, SEQ ID NO:43, and SEQ ID NO:44, SEQ ID NO:92, SEQ ID NO:93, and SEQ ID NO:94, SEQ ID NO:100, SEQ ID NO:101, and SEQ ID NO:102, SEQ ID NO:108, SEQ ID NO:109, and SEQ ID NO:110, SEQ ID NO:116, SEQ ID NO:117, and SEQ ID NO:118, SEQ ID NO:124, SEQ ID NO:125, and SEQ ID NO:126, SEQ ID NO:132, SEQ ID NO:133, and SEQ ID NO:134, and SEQ ID NO: 153, and SEQ ID NO: 154, and SEQ ID NO: 155. 
     
     
         11 . The isolated antibody or antibody fragment of  claim 1 , wherein the antibody or antibody fragment comprises a variable heavy domain that comprises complementarity-determining region (CDR) residues SEQ ID NO:2, SEQ ID NO:3, and SEQ ID NO:4, and a variable light domain that comprises complementarity-determining region (CDR) residues SEQ ID NO:6, SEQ ID NO:7, and SEQ ID NO:8. 
     
     
         12 . The isolated antibody or antibody fragment of  claim 1 , wherein the antibody or antibody fragment comprises a variable heavy domain that comprises complementarity-determining region (CDR) residues SEQ ID NO:10, SEQ ID NO:11, and SEQ ID NO:12, and a variable light domain that comprises complementarity-determining region (CDR) residues SEQ ID NO:14, SEQ ID NO:15, and SEQ ID NO:16. 
     
     
         13 . The isolated antibody or antibody fragment of  claim 1 , wherein the antibody or antibody fragment comprises a variable heavy domain that comprises complementarity-determining region (CDR) residues SEQ ID NO:18, SEQ ID NO:19, and SEQ ID NO:20, and a variable light domain that comprises complementarity-determining region (CDR) residues SEQ ID NO:22, SEQ ID NO:23, and SEQ ID NO:24. 
     
     
         14 . The isolated antibody or antibody fragment of  claim 1 , wherein the antibody or antibody fragment comprises a variable heavy domain that comprises complementarity-determining region (CDR) residues SEQ ID NO:26, SEQ ID NO:27, and SEQ ID NO:28, and a variable light domain that comprises complementarity-determining region (CDR) residues SEQ ID NO:30, SEQ ID NO:31, and SEQ ID NO:32. 
     
     
         15 . The isolated antibody or antibody fragment of  claim 1 , wherein the antibody or antibody fragment comprises a variable heavy domain that comprises complementaritydetermining region (CDR) residues SEQ ID NO:34, SEQ ID NO:35, and SEQ ID NO:36, and a variable light domain that comprises complementarity-determining region (CDR) residues SEQ ID NO:38, SEQ ID NO:39, and SEQ ID NO:40. 
     
     
         16 . The isolated antibody or antibody fragment of  claim 1 , wherein the antibody or antibody fragment comprises a variable heavy domain that comprises complementarity-determining region (CDR) residues SEQ ID NO:50, SEQ ID NO:51, and SEQ ID NO:52, and a variable light domain that comprises complementarity-determining region (CDR) residues SEQ ID NO:54, SEQ ID NO:55, and SEQ ID NO:56. 
     
     
         17 . The isolated antibody or antibody fragment of  claim 1 , wherein the antibody or antibody fragment comprises a variable heavy domain that comprises complementarity-determining region (CDR) residues SEQ ID NO:58, SEQ ID NO:59, and SEQ ID NO:60, and a variable light domain that comprises complementarity-determining region (CDR) residues SEQ ID NO:62, SEQ ID NO:63, and SEQ ID NO:64. 
     
     
         18 . The isolated antibody or antibody fragment of  claim 1 , wherein the antibody or antibody fragment comprises a variable heavy domain that comprises complementarity-determining region (CDR) residues SEQ ID NO:42, SEQ ID NO:43, and SEQ ID NO:44, and a variable light domain that comprises complementarity-determining region (CDR) residues SEQ ID NO:46, SEQ ID NO:47, and SEQ ID NO:48. 
     
     
         19 . The isolated antibody or antibody fragment of  claim 1 , wherein the antibody or antibody fragment comprises a variable heavy domain that comprises complementarity-determining region (CDR) residues SEQ ID NO:92 or 153, SEQ ID NO:93 or 154, and SEQ ID NO:94 or 155, and a variable light domain that comprises complementarity-determining region (CDR) residues SEQ ID NO:96 or 156, SEQ ID NO:97 or 157, and SEQ ID NO:98 or 158. 
     
     
         20 . The isolated antibody or antibody fragment of  claim 1 , wherein the antibody or antibody fragment comprises a variable heavy domain that comprises complementarity-determining region (CDR) residues SEQ ID NO:100, SEQ ID NO:101, and SEQ ID NO:102, and a variable light domain that comprises complementarity-determining region (CDR) residues SEQ ID NO:104, SEQ ID NO:105, and SEQ ID NO:106. 
     
     
         21 .- 47 . (canceled)