	US 12,441,796 B2
	Antibody constructs for CDH19 and CD3
Shouhua Xiao, Foster City, CA (US); Zheng Pan, Fremont, CA (US); Dineli Wickramasinghe, San Francisco, CA (US); M. Shawn Jeffries, Indianapolis, IN (US); Chadwick Terence King, North Vancouver (CA); Brian Mingtung Chan, Port Coquitlam (CA); Peter Kufer, Munich (DE); Ralf Lutterbüse, Munich (DE); Tobias Raum, Munich (DE); Patrick Hoffmann, Munich (DE); Doris Rau, Munich (DE); Roman Kischel, Munich (DE); Bryan Lemon, Mountain View, CA (US); and Holger Wesche, San Francisco, CA (US)
Assigned to AMGEN INC., Thousand Oaks, CA (US); and AMGEN RESEARCH (MUNICH) GMBH, Munich (DE)
Filed by AMGEN INC., Thousand Oaks, CA (US); and AMGEN RESEARCH (MUNICH) GMBH, Munich (DE)
Filed on Sep. 19, 2022, as Appl. No. 17/933,277.
Application 17/933,277 is a division of application No. 16/040,927, filed on Jul. 20, 2018, granted, now 11,498,964.
Application 16/040,927 is a division of application No. 14/761,839, granted, now 10,059,766, previously published as PCT/EP2014/051550, filed on Jan. 27, 2014.
Claims priority of provisional application 61/785,147, filed on Mar. 14, 2013.
Claims priority of provisional application 61/756,991, filed on Jan. 25, 2013.
Prior Publication US 2024/0010724 A1, Jan. 11, 2024
Int. Cl. C07K 16/28 (2006.01); A61K 47/60 (2017.01); C07K 16/30 (2006.01); C07K 16/46 (2006.01); A61K 39/00 (2006.01)

CPC C07K 16/2809 (2013.01) [A61K 47/60 (2017.08); C07K 16/28 (2013.01); C07K 16/2896 (2013.01); C07K 16/3053 (2013.01); C07K 16/468 (2013.01); A61K 2039/505 (2013.01); C07K 2317/21 (2013.01); C07K 2317/31 (2013.01); C07K 2317/33 (2013.01); C07K 2317/565 (2013.01); C07K 2317/569 (2013.01); C07K 2317/622 (2013.01); C07K 2317/626 (2013.01); C07K 2317/73 (2013.01); C07K 2317/77 (2013.01); C07K 2317/92 (2013.01); C07K 2319/00 (2013.01)]

17 Claims

1. An antibody construct or an oligomer thereof comprising a first binding domain which binds to human cadherin-19 (CDH19) on the surface of a target cell and a second binding domain which binds to human CD3 epsilon on the surface of a T cell, wherein the first binding domain comprises a VH region comprising CDR-H1, CDR-H2 and CDR-H3 and a VL region comprising CDR-L1, CDR-L2 and CDR-L3 selected from the group consisting of:

(a) CDR-H1 as set forth in SEQ ID NO: 4, CDR-H2 as set forth in SEQ ID NO: 5, CDR-H3 as set forth in SEQ ID NO: 6, CDR-L1 as set forth in SEQ ID NO: 172, CDR-L2 as set forth in SEQ ID NO: 173 and CDR-L3 as set forth in SEQ ID NO: 174;

(b) CDR-H1 as set forth in SEQ ID NO: 10, CDR-H2 as set forth in SEQ ID NO: 11, CDR-H3 as set forth in SEQ ID NO: 12, CDR-L1 as set forth in SEQ ID NO: 178, CDR-L2 as set forth in SEQ ID NO: 179 and CDR-L3 as set forth in SEQ ID NO: 180;

(c) CDR-H1 as set forth in SEQ ID NO: 28, CDR-H2 as set forth in SEQ ID NO: 29, CDR-H3 as set forth in SEQ ID NO: 30, CDR-L1 as set forth in SEQ ID NO: 196, CDR-L2 as set forth in SEQ ID NO: 197 and CDR-L3 as set forth in SEQ ID NO: 198;

(d) CDR-H1 as set forth in SEQ ID NO: 34, CDR-H2 as set forth in SEQ ID NO: 35, CDR-H3 as set forth in SEQ ID NO: 36, CDR-L1 as set forth in SEQ ID NO: 202, CDR-L2 as set forth in SEQ ID NO: 203 and CDR-L3 as set forth in SEQ ID NO: 204;

(e) CDR-H1 as set forth in SEQ ID NO: 46, CDR-H2 as set forth in SEQ ID NO: 47, CDR-H3 as set forth in SEQ ID NO: 48, CDR-L1 as set forth in SEQ ID NO: 214, CDR-L2 as set forth in SEQ ID NO: 215 and CDR-L3 as set forth in SEQ ID NO: 216;

(f) CDR-H1 as set forth in SEQ ID NO: 58, CDR-H2 as set forth in SEQ ID NO: 59, CDR-H3 as set forth in SEQ ID NO: 60, CDR-L1 as set forth in SEQ ID NO: 226, CDR-L2 as set forth in SEQ ID NO: 227 and CDR-L3 as set forth in SEQ ID NO: 228;

(g) CDR-H1 as set forth in SEQ ID NO: 64, CDR-H2 as set forth in SEQ ID NO: 65, CDR-H3 as set forth in SEQ ID NO: 66, CDR-L1 as set forth in SEQ ID NO: 232, CDR-L2 as set forth in SEQ ID NO: 233 and CDR-L3 as set forth in SEQ ID NO: 234;

(h) CDR-H1 as set forth in SEQ ID NO: 70, CDR-H2 as set forth in SEQ ID NO: 71, CDR-H3 as set forth in SEQ ID NO: 72, CDR-L1 as set forth in SEQ ID NO: 238, CDR-L2 as set forth in SEQ ID NO: 239 and CDR-L3 as set forth in SEQ ID NO: 240;

(i) CDR-H1 as set forth in SEQ ID NO: 160, CDR-H2 as set forth in SEQ ID NO: 161, CDR-H3 as set forth in SEQ ID NO: 162, CDR-L1 as set forth in SEQ ID NO: 328, CDR-L2 as set forth in SEQ ID NO: 329 and CDR-L3 as set forth in SEQ ID NO: 330;

(j) CDR-H1 as set forth in SEQ ID NO: 46, CDR-H2 as set forth in SEQ ID NO: 47, CDR-H3 as set forth in SEQ ID NO: 48, CDR-L1 as set forth in SEQ ID NO: 924, CDR-L2 as set forth in SEQ ID NO: 215 and CDR-L3 as set forth in SEQ ID NO: 216;

(k) CDR-H1 as set forth in SEQ ID NO: 46, CDR-H2 as set forth in SEQ ID NO: 47, CDR-H3 as set forth in SEQ ID NO: 902, CDR-L1 as set forth in SEQ ID NO: 924, CDR-L2 as set forth in SEQ ID NO: 215 and CDR-L3 as set forth in SEQ ID NO: 216;

(l) CDR-H1 as set forth in SEQ ID NO: 46, CDR-H2 as set forth in SEQ ID NO: 47, CDR-H3 as set forth in SEQ ID NO: 903, CDR-L1 as set forth in SEQ ID NO: 924, CDR-L2 as set forth in SEQ ID NO: 215 and CDR-L3 as set forth in SEQ ID NO: 216;

(m) CDR-H1 as set forth in SEQ ID NO: 46, CDR-H2 as set forth in SEQ ID NO: 47, CDR-H3 as set forth in SEQ ID NO: 48, CDR-L1 as set forth in SEQ ID NO: 925, CDR-L2 as set forth in SEQ ID NO: 215 and CDR-L3 as set forth in SEQ ID NO: 216;

(n) CDR-H1 as set forth in SEQ ID NO: 70, CDR-H2 as set forth in SEQ ID NO: 907, CDR-H3 as set forth in SEQ ID NO: 72, CDR-L1 as set forth in SEQ ID NO: 238, CDR-L2 as set forth in SEQ ID NO: 239 and CDR-L3 as set forth in SEQ ID NO: 240;

(o) CDR-H1 as set forth in SEQ ID NO: 70, CDR-H2 as set forth in SEQ ID NO: 907, CDR-H3 as set forth in SEQ ID NO: 908, CDR-L1 as set forth in SEQ ID NO: 238, CDR-L2 as set forth in SEQ ID NO: 239 and CDR-L3 as set forth in SEQ ID NO: 240;

(p) CDR-H1 as set forth in SEQ ID NO: 28, CDR-H2 as set forth in SEQ ID NO: 901, CDR-H3 as set forth in SEQ ID NO: 30, CDR-L1 as set forth in SEQ ID NO: 922, CDR-L2 as set forth in SEQ ID NO: 197 and CDR-L3 as set forth in SEQ ID NO: 923;

(q) CDR-H1 as set forth in SEQ ID NO: 58, CDR-H2 as set forth in SEQ ID NO: 905, CDR-H3 as set forth in SEQ ID NO: 906, CDR-L1 as set forth in SEQ ID NO: 226, CDR-L2 as set forth in SEQ ID NO: 227 and CDR-L3 as set forth in SEQ ID NO: 228;

(r) CDR-H1 as set forth in SEQ ID NO: 58, CDR-H2 as set forth in SEQ ID NO: 905, CDR-H3 as set forth in SEQ ID NO: 60, CDR-L1 as set forth in SEQ ID NO: 226, CDR-L2 as set forth in SEQ ID NO: 227 and CDR-L3 as set forth in SEQ ID NO: 228;

(s) CDR-H1 as set forth in SEQ ID NO: 160, CDR-H2 as set forth in SEQ ID NO: 161, CDR-H3 as set forth in SEQ ID NO: 162, CDR-L1 as set forth in SEQ ID NO: 939, CDR-L2 as set forth in SEQ ID NO: 329 and CDR-L3 as set forth in SEQ ID NO: 330;

(t) CDR-H1 as set forth in SEQ ID NO: 160, CDR-H2 as set forth in SEQ ID NO: 921, CDR-H3 as set forth in SEQ ID NO: 162, CDR-L1 as set forth in SEQ ID NO: 939, CDR-L2 as set forth in SEQ ID NO: 329 and CDR-L3 as set forth in SEQ ID NO: 940;

(u) CDR-H1 as set forth in SEQ ID NO: 160, CDR-H2 as set forth in SEQ ID NO: 161, CDR-H3 as set forth in SEQ ID NO: 162, CDR-L1 as set forth in SEQ ID NO: 941, CDR-L2 as set forth in SEQ ID NO: 329 and CDR-L3 as set forth in SEQ ID NO: 330;

(v) CDR-H1 as set forth in SEQ ID NO: 28, CDR-H2 as set forth in SEQ ID NO: 29, CDR-H3 as set forth in SEQ ID NO: 30, CDR-L1 as set forth in SEQ ID NO: 196, CDR-L2 as set forth in SEQ ID NO: 197 and CDR-L3 as set forth in SEQ ID NO: 923;

(w) CDR-H1 as set forth in SEQ ID NO: 28, CDR-H2 as set forth in SEQ ID NO: 29, CDR-H3 as set forth in SEQ ID NO: 30, CDR-L1 as set forth in SEQ ID NO: 922, CDR-L2 as set forth in SEQ ID NO: 197 and CDR-L3 as set forth in SEQ ID NO: 923;

(x) CDR-H1 as set forth in SEQ ID NO: 28, CDR-H2 as set forth in SEQ ID NO: 901, CDR-H3 as set forth in SEQ ID NO: 30, CDR-L1 as set forth in SEQ ID NO: 922, CDR-L2 as set forth in SEQ ID NO: 197 and CDR-L3 as set forth in SEQ ID NO: 923;

(y) CDR-H1 as set forth in SEQ ID NO: 28, CDR-H2 as set forth in SEQ ID NO: 29, CDR-H3 as set forth in SEQ ID NO: 30, CDR-L1 as set forth in SEQ ID NO: 939, CDR-L2 as set forth in SEQ ID NO: 329 and CDR-L3 as set forth in SEQ ID NO: 330;

(z) CDR-H1 as set forth in SEQ ID NO: 970, CDR-H2 as set forth in SEQ ID NO: 971, CDR-H3 as set forth in SEQ ID NO: 972, CDR-L1 as set forth in SEQ ID NO: 973, CDR-L2 as set forth in SEQ ID NO: 974 and CDR-L3 as set forth in SEQ ID NO: 975;

(aa) CDR-H1 as set forth in SEQ ID NO: 1061, CDR-H2 as set forth in SEQ ID NO: 1062, CDR-H3 as set forth in SEQ ID NO: 1063, CDR-L1 as set forth in SEQ ID NO: 1064, CDR-L2 as set forth in SEQ ID NO: 1065 and CDR-L3 as set forth in SEQ ID NO: 1066;

(ab) CDR-H1 as set forth in SEQ ID NO: 1139, CDR-H2 as set forth in SEQ ID NO: 1140, CDR-H3 as set forth in SEQ ID NO: 1141, CDR-L1 as set forth in SEQ ID NO: 1142, CDR-L2 as set forth in SEQ ID NO: 1143 and CDR-L3 as set forth in SEQ ID NO: 1144;

(ac) CDR-H1 as set forth in SEQ ID NO: 1152, CDR-H2 as set forth in SEQ ID NO: 1153, CDR-H3 as set forth in SEQ ID NO: 1154, CDR-L1 as set forth in SEQ ID NO: 1155, CDR-L2 as set forth in SEQ ID NO: 1156 and CDR-L3 as set forth in SEQ ID NO: 1157;

(ad) CDR-H1 as set forth in SEQ ID NO: 1178, CDR-H2 as set forth in SEQ ID NO: 1179, CDR-H3 as set forth in SEQ ID NO: 1180, CDR-L1 as set forth in SEQ ID NO: 1181, CDR-L2 as set forth in SEQ ID NO: 1182 and CDR-L3 as set forth in SEQ ID NO: 1183;

(ae) CDR-H1 as set forth in SEQ ID NO: 1191, CDR-H2 as set forth in SEQ ID NO: 1192, CDR-H3 as set forth in SEQ ID NO: 1193, CDR-L1 as set forth in SEQ ID NO: 1194, CDR-L2 as set forth in SEQ ID NO: 1195 and CDR-L3 as set forth in SEQ ID NO: 1196;

(af) CDR-H1 as set forth in SEQ ID NO: 1204, CDR-H2 as set forth in SEQ ID NO: 1205, CDR-H3 as set forth in SEQ ID NO: 1206, CDR-L1 as set forth in SEQ ID NO: 1207, CDR-L2 as set forth in SEQ ID NO: 1208 and CDR-L3 as set forth in SEQ ID NO: 1209;

(ag) CDR-H1 as set forth in SEQ ID NO: 1217, CDR-H2 as set forth in SEQ ID NO: 1218, CDR-H3 as set forth in SEQ ID NO: 1219, CDR-L1 as set forth in SEQ ID NO: 1220, CDR-L2 as set forth in SEQ ID NO: 1221 and CDR-L3 as set forth in SEQ ID NO: 1222;

(ah) CDR-H1 as set forth in SEQ ID NO: 1230, CDR-H2 as set forth in SEQ ID NO: 1231, CDR-H3 as set forth in SEQ ID NO: 1232, CDR-L1 as set forth in SEQ ID NO: 1233, CDR-L2 as set forth in SEQ ID NO: 1234 and CDR-L3 as set forth in SEQ ID NO: 1235;

(ai) CDR-H1 as set forth in SEQ ID NO: 1308, CDR-H2 as set forth in SEQ ID NO: 1309, CDR-H3 as set forth in SEQ ID NO: 1310, CDR-L1 as set forth in SEQ ID NO: 1311, CDR-L2 as set forth in SEQ ID NO: 1312 and CDR-L3 as set forth in SEQ ID NO: 1313;

(aj) CDR-H1 as set forth in SEQ ID NO: 1321, CDR-H2 as set forth in SEQ ID NO: 1322, CDR-H3 as set forth in SEQ ID NO: 1323, CDR-L1 as set forth in SEQ ID NO: 1324, CDR-L2 as set forth in SEQ ID NO: 1325 and CDR-L3 as set forth in SEQ ID NO: 1326;

(ak) CDR-H1 as set forth in SEQ ID NO: 1373, CDR-H2 as set forth in SEQ ID NO: 1374, CDR-H3 as set forth in SEQ ID NO: 1375, CDR-L1 as set forth in SEQ ID NO: 1376, CDR-L2 as set forth in SEQ ID NO: 1377 and CDR-L3 as set forth in SEQ ID NO: 1378;

(al) CDR-H1 as set forth in SEQ ID NO: 1386, CDR-H2 as set forth in SEQ ID NO: 1387, CDR-H3 as set forth in SEQ ID NO: 1388, CDR-L1 as set forth in SEQ ID NO: 1389, CDR-L2 as set forth in SEQ ID NO: 1390 and CDR-L3 as set forth in SEQ ID NO: 1391;

(am) CDR-H1 as set forth in SEQ ID NO: 1399, CDR-H2 as set forth in SEQ ID NO: 1400, CDR-H3 as set forth in SEQ ID NO: 1401, CDR-L1 as set forth in SEQ ID NO: 1402, CDR-L2 as set forth in SEQ ID NO: 1403 and CDR-L3 as set forth in SEQ ID NO: 1404;

(an) CDR-H1 as set forth in SEQ ID NO: 1412, CDR-H2 as set forth in SEQ ID NO: 1413, CDR-H3 as set forth in SEQ ID NO: 1414, CDR-L1 as set forth in SEQ ID NO: 1415, CDR-L2 as set forth in SEQ ID NO: 1416 and CDR-L3 as set forth in SEQ ID NO: 1417;

(ao) CDR-H1 as set forth in SEQ ID NO: 1777, CDR-H2 as set forth in SEQ ID NO: 1778, CDR-H3 as set forth in SEQ ID NO: 1779, CDR-L1 as set forth in SEQ ID NO: 1780, CDR-L2 as set forth in SEQ ID NO: 1781 and CDR-L3 as set forth in SEQ ID NO: 1782;

(ap) CDR-H1 as set forth in SEQ ID NO: 1790, CDR-H2 as set forth in SEQ ID NO: 1791, CDR-H3 as set forth in SEQ ID NO: 1792, CDR-L1 as set forth in SEQ ID NO: 1793, CDR-L2 as set forth in SEQ ID NO: 1794 and CDR-L3 as set forth in SEQ ID NO: 1795;

(aq) CDR-H1 as set forth in SEQ ID NO: 1803, CDR-H2 as set forth in SEQ ID NO: 1804, CDR-H3 as set forth in SEQ ID NO: 1805, CDR-L1 as set forth in SEQ ID NO: 1806, CDR-L2 as set forth in SEQ ID NO: 1807 and CDR-L3 as set forth in SEQ ID NO: 1808;

(ar) CDR-H1 as set forth in SEQ ID NO: 1816, CDR-H2 as set forth in SEQ ID NO: 1817, CDR-H3 as set forth in SEQ ID NO: 1818, CDR-L1 as set forth in SEQ ID NO: 1819, CDR-L2 as set forth in SEQ ID NO: 1820 and CDR-L3 as set forth in SEQ ID NO: 1821;

(as) CDR-H1 as set forth in SEQ ID NO: 1829, CDR-H2 as set forth in SEQ ID NO: 1830, CDR-H3 as set forth in SEQ ID NO: 1831, CDR-L1 as set forth in SEQ ID NO: 1832, CDR-L2 as set forth in SEQ ID NO: 1833 and CDR-L3 as set forth in SEQ ID NO: 1834;

(at) CDR-H1 as set forth in SEQ ID NO: 1842, CDR-H2 as set forth in SEQ ID NO: 1843, CDR-H3 as set forth in SEQ ID NO: 1844, CDR-L1 as set forth in SEQ ID NO: 1845, CDR-L2 as set forth in SEQ ID NO: 1846 and CDR-L3 as set forth in SEQ ID NO: 1847;

(au) CDR-H1 as set forth in SEQ ID NO: 1855, CDR-H2 as set forth in SEQ ID NO: 1856, CDR-H3 as set forth in SEQ ID NO: 1857, CDR-L1 as set forth in SEQ ID NO: 1858, CDR-L2 as set forth in SEQ ID NO: 1859 and CDR-L3 as set forth in SEQ ID NO: 1860;

(av) CDR-H1 as set forth in SEQ ID NO: 1868, CDR-H2 as set forth in SEQ ID NO: 1869, CDR-H3 as set forth in SEQ ID NO: 1870, CDR-L1 as set forth in SEQ ID NO: 1871, CDR-L2 as set forth in SEQ ID NO: 1872 and CDR-L3 as set forth in SEQ ID NO: 1873;

(aw) CDR-H1 as set forth in SEQ ID NO: 1881, CDR-H2 as set forth in SEQ ID NO: 1882, CDR-H3 as set forth in SEQ ID NO: 1883, CDR-L1 as set forth in SEQ ID NO: 1884, CDR-L2 as set forth in SEQ ID NO: 1885 and CDR-L3 as set forth in SEQ ID NO: 1886;

(ax) CDR-H1 as set forth in SEQ ID NO: 2063, CDR-H2 as set forth in SEQ ID NO: 2064, CDR-H3 as set forth in SEQ ID NO: 2065, CDR-L1 as set forth in SEQ ID NO: 2066, CDR-L2 as set forth in SEQ ID NO: 2067 and CDR-L3 as set forth in SEQ ID NO: 2068;

(ay) CDR-H1 as set forth in SEQ ID NO: 2076, CDR-H2 as set forth in SEQ ID NO: 2077, CDR-H3 as set forth in SEQ ID NO: 2078, CDR-L1 as set forth in SEQ ID NO: 2079, CDR-L2 as set forth in SEQ ID NO: 2080 and CDR-L3 as set forth in SEQ ID NO: 2081;

(az) CDR-H1 as set forth in SEQ ID NO: 2089, CDR-H2 as set forth in SEQ ID NO: 2090, CDR-H3 as set forth in SEQ ID NO: 2091, CDR-L1 as set forth in SEQ ID NO: 2092, CDR-L2 as set forth in SEQ ID NO: 2093 and CDR-L3 as set forth in SEQ ID NO: 2094;

(aaa) CDR-H1 as set forth in SEQ ID NO: 2102, CDR-H2 as set forth in SEQ ID NO: 2103, CDR-H3 as set forth in SEQ ID NO: 2104, CDR-L1 as set forth in SEQ ID NO: 2105, CDR-L2 as set forth in SEQ ID NO: 2106 and CDR-L3 as set forth in SEQ ID NO: 2107;

(aab) CDR-H1 as set forth in SEQ ID NO: 2115, CDR-H2 as set forth in SEQ ID NO: 2116, CDR-H3 as set forth in SEQ ID NO: 2117, CDR-L1 as set forth in SEQ ID NO: 2118, CDR-L2 as set forth in SEQ ID NO: 2119 and CDR-L3 as set forth in SEQ ID NO: 2120;

(aac) CDR-H1 as set forth in SEQ ID NO: 2128, CDR-H2 as set forth in SEQ ID NO: 2129, CDR-H3 as set forth in SEQ ID NO: 2130, CDR-L1 as set forth in SEQ ID NO: 2131, CDR-L2 as set forth in SEQ ID NO: 2132 and CDR-L3 as set forth in SEQ ID NO: 2133;

(aad) CDR-H1 as set forth in SEQ ID NO: 2141, CDR-H2 as set forth in SEQ ID NO: 2142, CDR-H3 as set forth in SEQ ID NO: 2143, CDR-L1 as set forth in SEQ ID NO: 2144, CDR-L2 as set forth in SEQ ID NO: 2145 and CDR-L3 as set forth in SEQ ID NO: 2146;

(aae) CDR-H1 as set forth in SEQ ID NO: 2154, CDR-H2 as set forth in SEQ ID NO: 2155, CDR-H3 as set forth in SEQ ID NO: 2156, CDR-L1 as set forth in SEQ ID NO: 2157, CDR-L2 as set forth in SEQ ID NO: 2158 and CDR-L3 as set forth in SEQ ID NO: 2159;

(aaf) CDR-H1 as set forth in SEQ ID NO: 2180, CDR-H2 as set forth in SEQ ID NO: 2181, CDR-H3 as set forth in SEQ ID NO: 2182, CDR-L1 as set forth in SEQ ID NO: 2183, CDR-L2 as set forth in SEQ ID NO: 2184 and CDR-L3 as set forth in SEQ ID NO: 2185;

(aag) CDR-H1 as set forth in SEQ ID NO: 2193, CDR-H2 as set forth in SEQ ID NO: 2194, CDR-H3 as set forth in SEQ ID NO: 2195, CDR-L1 as set forth in SEQ ID NO: 2196, CDR-L2 as set forth in SEQ ID NO: 2197 and CDR-L3 as set forth in SEQ ID NO: 2198; and

(aah) CDR-H1 as set forth in SEQ ID NO: 2206, CDR-H2 as set forth in SEQ ID NO: 2207, CDR-H3 as set forth in SEQ ID NO: 2208, CDR-L1 as set forth in SEQ ID NO: 2209, CDR-L2 as set forth in SEQ ID NO: 2210 and CDR-L3 as set forth in SEQ ID NO: 2211.