Therapeutic DLL4 binding proteins

1. A binding protein comprising an antigen binding domain, said binding protein being capable of binding human DLL4, said antigen binding domain comprising six CDRs: CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR-L3, wherein:

CDR-H1 is selected from the group consisting of:

residues 31-37 of SEQ ID NO:1;

SEQ ID NO:117;

SEQ ID NO:121;

SEQ ID NO:125;

SEQ ID NO:129;

SEQ ID NO:133;

SEQ ID NO:137;

SEQ ID NO:141;

SEQ ID NO:145;

SEQ ID NO:149;

SEQ ID NO:153;

SEQ ID NO:157;

SEQ ID NO:161;

SEQ ID NO:165;

SEQ ID NO:169;

SEQ ID NO:173;

SEQ ID NO:177;

SEQ ID NO:181;

SEQ ID NO:185;

SEQ ID NO:189;

SEQ ID NO:193;

SEQ ID NO:197;

SEQ ID NO:201;

SEQ ID NO:205;

SEQ ID NO:209;

SEQ ID NO:213;

residues 31-37 of SEQ ID NO:334;

residues 31-37 of SEQ ID NO:336;

residues 31-37 of SEQ ID NO:338;

residues 31-37 of SEQ ID NO:340;

residues 31-37 of SEQ ID NO:342;

residues 31-37 of SEQ ID NO:344;

residues 31-37 of SEQ ID NO:346;

residues 31-37 of SEQ ID NO:348;

residues 31-37 of SEQ ID NO:350;

residues 31-37 of SEQ ID NO:352;

residues 31-37 of SEQ ID NO:354;

residues 31-37 of SEQ ID NO:356;

residues 31-37 of SEQ ID NO:358; and

residues 31-37 of SEQ ID NO:360;

CDR-H2, selected from the group consisting of:

residues 52-67 of SEQ ID NO:1;

SEQ ID NO:118;

SEQ ID NO:122;

SEQ ID NO:126;

SEQ ID NO:130;

SEQ ID NO:134;

SEQ ID NO:138;

SEQ ID NO:142;

SEQ ID NO:146;

SEQ ID NO:150;

SEQ ID NO:154;

SEQ ID NO:158;

SEQ ID NO:162;

SEQ ID NO:166;

SEQ ID NO:170;

SEQ ID NO:174;

SEQ ID NO:178;

SEQ ID NO:182;

SEQ ID NO:186;

SEQ ID NO:190;

SEQ ID NO:194;

SEQ ID NO:198;

SEQ ID NO:202;

SEQ ID NO:206;

SEQ ID NO:210;

SEQ ID NO:214;

residues 52-67 of SEQ ID NO:334;

residues 52-67 of SEQ ID NO:336;

residues 52-67 of SEQ ID NO:338;

residues 52-67 of SEQ ID NO:340;

residues 52-67 of SEQ ID NO:342;

residues 52-67 of SEQ ID NO:344;

residues 52-67 of SEQ ID NO:346;

residues 52-67 of SEQ ID NO:348;

residues 52-67 of SEQ ID NO:350;

residues 52-67 of SEQ ID NO:352;

residues 52-67 of SEQ ID NO:354;

residues 52-67 of SEQ ID NO:356;

residues 52-67 of SEQ ID NO:358; and

residues 52-67 of SEQ ID NO:360;

CDR-H3 is selected from the group consisting of:

residues 100-110 of SEQ ID NO:1;

SEQ ID NO:119;

SEQ ID NO:123;

SEQ ID NO:127;

SEQ ID NO:131;

SEQ ID NO:135;

SEQ ID NO:139;

SEQ ID NO:143;

SEQ ID NO:147;

SEQ ID NO:151;

SEQ ID NO:155;

SEQ ID NO:159;

SEQ ID NO:163;

SEQ ID NO:167;

SEQ ID NO:171;

SEQ ID NO:175;

SEQ ID NO:179;

SEQ ID NO:183;

SEQ ID NO:187;

SEQ ID NO:191;

SEQ ID NO:195;

SEQ ID NO:199;

SEQ ID NO:203;

SEQ ID NO:207;

SEQ ID NO:211;

SEQ ID NO:215;

residues 100-110 of SEQ ID NO:334;

residues 100-110 of SEQ ID NO:336;

residues 100-110 of SEQ ID NO:338;

residues 100-110 of SEQ ID NO:340;

residues 100-110 of SEQ ID NO:342;

residues 100-110 of SEQ ID NO:344;

residues 100-110 of SEQ ID NO:346;

residues 100-110 of SEQ ID NO:348;

residues 100-110 of SEQ ID NO:350;

residues 100-110 of SEQ ID NO:352;

residues 100-110 of SEQ ID NO:354;

residues 100-110 of SEQ ID NO:356;

residues 100-110 of SEQ ID NO:358; and

residues 100-110 of SEQ ID NO:360;

CDR-L1 is selected from the group consisting of:

residues 23-33 of SEQ ID NO:111;

SEQ ID NO:217;

SEQ ID NO:221;

SEQ ID NO:225;

SEQ ID NO:229;

SEQ ID NO:233;

SEQ ID NO:237;

SEQ ID NO:241;

SEQ ID NO:245;

SEQ ID NO:249;

SEQ ID NO:253;

SEQ ID NO:257;

SEQ ID NO:261;

SEQ ID NO:265;

SEQ ID NO:269;

SEQ ID NO:273;

SEQ ID NO:277;

SEQ ID NO:281;

SEQ ID NO:285;

SEQ ID NO:289;

SEQ ID NO:293;

SEQ ID NO:297;

SEQ ID NO:301;

SEQ ID NO:305;

SEQ ID NO:309;

SEQ ID NO:313;

residues 23-33 of SEQ ID NO:335;

residues 23-33 of SEQ ID NO:337;

residues 23-33 of SEQ ID NO:339;

residues 23-33 of SEQ ID NO:341;

residues 23-33 of SEQ ID NO:343;

residues 24-34 of SEQ ID NO:345;

residues 23-33 of SEQ ID NO:347;

residues 24-34 of SEQ ID NO:349;

residues 24-34 of SEQ ID NO:351;

residues 24-34 of SEQ ID NO:353;

residues 24-34 of SEQ ID NO:355;

residues 23-33 of SEQ ID NO:357;

residues 23-33 of SEQ ID NO:359; and

residues 23-33 of SEQ ID NO:361;

CDR-L2 is selected from the group consisting of:

residues 49-55 of SEQ ID NO:111;

SEQ ID NO:230;

SEQ ID NO:234;

SEQ ID NO:238;

SEQ ID NO:242;

SEQ ID NO:246;

SEQ ID NO:250;

SEQ ID NO:254;

SEQ ID NO:258;

SEQ ID NO:262;

SEQ ID NO:266;

SEQ ID NO:270;

SEQ ID NO:218;

SEQ ID NO:222;

SEQ ID NO:226;

SEQ ID NO:274;

SEQ ID NO:278;

SEQ ID NO:302;

SEQ ID NO:294;

SEQ ID NO:282;

SEQ ID NO:290;

SEQ ID NO:298;

SEQ ID NO:286;

SEQ ID NO:306;

SEQ ID NO:310;

SEQ ID NO:314;

residues 49-55 of SEQ ID NO:335;

residues 49-55 of SEQ ID NO:337;

residues 49-55 of SEQ ID NO:339;

residues 49-55 of SEQ ID NO:341;

residues 49-55 of SEQ ID NO:343;

residues 50-56 of SEQ ID NO:345;

residues 49-55 of SEQ ID NO:347;

residues 50-56 of SEQ ID NO:349;

residues 50-56 of SEQ ID NO:351;

residues 50-56 of SEQ ID NO:353;

residues 50-56 of SEQ ID NO:355;

residues 49-55 of SEQ ID NO:357;

residues 49-55 of SEQ ID NO:359; and

residues 49-55 of SEQ ID NO:361;

and

CDR-L3 is selected from the group consisting of:

residues 88-96 of SEQ ID NO:111;

SEQ ID NO:231;

SEQ ID NO:235;

SEQ ID NO:239;

SEQ ID NO:243;

SEQ ID NO:247;

SEQ ID NO:251;

SEQ ID NO:255;

SEQ ID NO:259;

SEQ ID NO:263;

SEQ ID NO:267;

SEQ ID NO:271;

SEQ ID NO:219;

SEQ ID NO:223;

SEQ ID NO:227;

SEQ ID NO:275;

SEQ ID NO:279;

SEQ ID NO:303;

SEQ ID NO:295;

SEQ ID NO:283;

SEQ ID NO:291;

SEQ ID NO:299;

SEQ ID NO:287;

SEQ ID NO:307;

SEQ ID NO:311;

SEQ ID NO:315;

residues 88-96 of SEQ ID NO:335;

residues 88-96 of SEQ ID NO:337;

residues 88-96 of SEQ ID NO:339;

residues 88-96 of SEQ ID NO:341;

residues 88-96 of SEQ ID NO:343;

residues 89-97 of SEQ ID NO:345;

residues 88-96 of SEQ ID NO:347;

residues 89-97 of SEQ ID NO:349;

residues 89-97 of SEQ ID NO:351;

residues 89-97 of SEQ ID NO:353;

residues 89-97 of SEQ ID NO:355;

residues 88-96 of SEQ ID NO:357;

residues 88-96 of SEQ ID NO:359; and

residues 88-96 of SEQ ID NO:361.

2. The binding protein according to claim 1 , wherein at least one said CDR comprises an amino acid sequence selected from the group consisting of:

residues 31-37 of SEQ ID NO:1 (CDR-H1); residues 52-67 of SEQ ID NO:1 (CDR-H2); residues 100-110 of SEQ ID NO:1 (CDR-H3);

residues 23-33 of SEQ ID NO:111 (CDR-L1); residues 49-55 of SEQ ID NO:111 (CDR-L2); residues 88-96 of SEQ ID NO:111 (CDR-L3);

SEQ ID NO:117 (CDR-H1); SEQ ID NO:118 (CDR-H2); SEQ ID NO:119 (CDR-H3);

SEQ ID NO:121 (CDR-H1); SEQ ID NO:122 (CDR-H2); SEQ ID NO:123 (CDR-H3);

SEQ ID NO:125 (CDR-H1); SEQ ID NO:126 (CDR-H2); SEQ ID NO:127 (CDR-H3);

SEQ ID NO:129 (CDR-H1); SEQ ID NO:130 (CDR-H2); SEQ ID NO:131 (CDR-H3);

SEQ ID NO:133 (CDR-H1); SEQ ID NO:134 (CDR-H2); SEQ ID NO:135 (CDR-H3);

SEQ ID NO:137 (CDR-H1); SEQ ID NO:138 (CDR-H2); SEQ ID NO:139 (CDR-H3);

SEQ ID NO:141 (CDR-H1); SEQ ID NO:142 (CDR-H2); SEQ ID NO:143 (CDR-H3);

SEQ ID NO:145 (CDR-H1); SEQ ID NO:146 (CDR-H2); SEQ ID NO:147 (CDR-H3);

SEQ ID NO:149 (CDR-H1); SEQ ID NO:150 (CDR-H2); SEQ ID NO:151 (CDR-H3); SEQ ID NO:153 (CDR-H1); SEQ ID NO:154 (CDR-H2); SEQ ID NO:155 (CDR-H3); SEQ ID NO:157 (CDR-H1); SEQ ID NO:158 (CDR-H2); SEQ ID NO:159 (CDR-H3); SEQ ID NO:161 (CDR-H1); SEQ ID NO:162 (CDR-H2); SEQ ID NO:163 (CDR-H3); SEQ ID NO:165 (CDR-H1); SEQ ID NO:166 (CDR-H2); SEQ ID NO:167 (CDR-H3); SEQ ID NO:169 (CDR-H1); SEQ ID NO:170 (CDR-H2); SEQ ID NO:171 (CDR-H3); SEQ ID NO:173 (CDR-H1); SEQ ID NO:174 (CDR-H2); SEQ ID NO:175 (CDR-H3); SEQ ID NO:177 (CDR-H1); SEQ ID NO:178 (CDR-H2); SEQ ID NO:179 (CDR-H3); SEQ ID NO:181 (CDR-H1); SEQ ID NO:182 (CDR-H2); SEQ ID NO:183 (CDR-H3); SEQ ID NO:185 (CDR-H1); SEQ ID NO:186 (CDR-H2); SEQ ID NO:187 (CDR-H3); SEQ ID NO:189 (CDR-H1); SEQ ID NO:190 (CDR-H2); SEQ ID NO:191 (CDR-H3); SEQ ID NO:193 (CDR-H1); SEQ ID NO:194 (CDR-H2); SEQ ID NO:195 (CDR-H3);

SEQ ID NO:197 (CDR-H1); SEQ ID NO:198 (CDR-H2); SEQ ID NO:199 (CDR-H3); SEQ ID NO:201 (CDR-H1); SEQ ID NO:202 (CDR-H2); SEQ ID NO:203 (CDR-H3);

SEQ ID NO:205 (CDR-H1); SEQ ID NO:206 (CDR-H2); SEQ ID NO:207 (CDR-H3); SEQ ID NO:209 (CDR-H1); SEQ ID NO:210 (CDR-H2); SEQ ID NO:211 (CDR-H3); SEQ ID NO:213 (CDR-H1); SEQ ID NO:214 (CDR-H2); SEQ ID NO:215 (CDR-H3); SEQ ID NO:217 (CDR-L1); SEQ ID NO:218 (CDR-L2); SEQ ID NO:219 (CDR-L3); SEQ ID NO:221 (CDR-L1); SEQ ID NO:222 (CDR-L2); SEQ ID NO:223 (CDR-L3); SEQ ID NO:225 (CDR-L1); SEQ ID NO:226 (CDR-L2); SEQ ID NO:227 (CDR-L3); SEQ ID NO:229 (CDR-L1); SEQ ID NO:230 (CDR-L2); SEQ ID NO:231 (CDR-L3); SEQ ID NO:233 (CDR-L1); SEQ ID NO:234 (CDR-L2); SEQ ID NO:235 (CDR-L3); SEQ ID NO:237 (CDR-L1); SEQ ID NO:238 (CDR-L2); SEQ ID NO:239 (CDR-L3); SEQ ID NO:241 (CDR-L1); SEQ ID NO:242 (CDR-L2); SEQ ID NO:243 (CDR-L3); SEQ ID NO:245 (CDR-L1); SEQ ID NO:246 (CDR-L2); SEQ ID NO:247 (CDR-L3); SEQ ID NO:249 (CDR-L1); SEQ ID NO:250 (CDR-L2); SEQ ID NO:251 (CDR-L3); SEQ ID NO:253 (CDR-L1); SEQ ID NO:254 (CDR-L2); SEQ ID NO:255 (CDR-L3); SEQ ID NO:257 (CDR-L1); SEQ ID NO:258 (CDR-L2); SEQ ID NO:259 (CDR-L3); SEQ ID NO:261 (CDR-L1); SEQ ID NO:262 (CDR-L2); SEQ ID NO:263 (CDR-L3); SEQ ID NO:265 (CDR-L1); SEQ ID NO:266 (CDR-L2); SEQ ID NO:267 (CDR-L3); SEQ ID NO:269 (CDR-L1); SEQ ID NO:270 (CDR-L2); SEQ ID NO:271 (CDR-L3); SEQ ID NO:273 (CDR-L1); SEQ ID NO:274 (CDR-L2); SEQ ID NO:275 (CDR-L3); SEQ ID NO:277 (CDR-L1); SEQ ID NO:278 (CDR-L2); SEQ ID NO:279 (CDR-L3); SEQ ID NO:281 (CDR-L1); SEQ ID NO:282 (CDR-L2); SEQ ID NO:283 (CDR-L3); SEQ ID NO:285 (CDR-L1); SEQ ID NO:286 (CDR-L2); SEQ ID NO:287 (CDR-L3); SEQ ID NO:289 (CDR-L1); SEQ ID NO:290 (CDR-L2); SEQ ID NO:291 (CDR-L3); SEQ ID NO:293 (CDR-L1); SEQ ID NO:294 (CDR-L2); SEQ ID NO:295 (CDR-L3); SEQ ID NO:297 (CDR-L1); SEQ ID NO:298 (CDR-L2); SEQ ID NO:299 (CDR-L3); SEQ ID NO:301 (CDR-L1); SEQ ID NO:302 (CDR-L2); SEQ ID NO:303 (CDR-L3); SEQ ID NO:305 (CDR-L1); SEQ ID NO:306 (CDR-L2); SEQ ID NO:307 (CDR-L3); SEQ ID NO:309 (CDR-L1); SEQ ID NO:310 (CDR-L2); SEQ ID NO:311 (CDR-L3); SEQ ID NO:313 (CDR-L1); SEQ ID NO:314 (CDR-L2); SEQ ID NO:315 (CDR-L3);

residues 31-37 of SEQ ID NO:334 (CDR-H1); residues 52-67 of SEQ ID NO:334 (CDR-H2); residues 100-110 of SEQ ID NO:334 (CDR-H3);

residues 23-33 of SEQ ID NO:335 (CDR-L1); residues 49-55 of SEQ ID NO:335 (CDR-L2); residues 88-96 of SEQ ID NO:335 (CDR-L3);

residues 31-37 of SEQ ID NO:336 (CDR-H1); residues 52-67 of SEQ ID NO:336 (CDR-H2); residues 100-110 of SEQ ID NO:336 (CDR-H3);

residues 23-33 of SEQ ID NO:337 (CDR-L1); residues 49-55 of SEQ ID NO:337 (CDR-L2); residues 88-96 of SEQ ID NO:337 (CDR-L3);

residues 31-37 of SEQ ID NO:338 (CDR-H1); residues 52-67 of SEQ ID NO:338 (CDR-H2); residues 100-110 of SEQ ID NO:338 (CDR-H3);

residues 23-33 of SEQ ID NO:339 (CDR-L1); residues 49-55 of SEQ ID NO:339 (CDR-L2); residues 88-96 of SEQ ID NO:339 (CDR-L3);

residues 31-37 of SEQ ID NO:340 (CDR-H1); residues 52-67 of SEQ ID NO:340 (CDR-H2); residues 100-110 of SEQ ID NO:340 (CDR-H3);

residues 23-33 of SEQ ID NO:341 (CDR-L1); residues 49-55 of SEQ ID NO:341 (CDR-L2); residues 88-96 of SEQ ID NO:341 (CDR-L3);

residues 31-37 of SEQ ID NO:342 (CDR-H1); residues 52-67 of SEQ ID NO:342 (CDR-H2); residues 100-110 of SEQ ID NO:342 (CDR-H3);

residues 23-33 of SEQ ID NO:343 (CDR-L1); residues 49-55 of SEQ ID NO:343 (CDR-L2); residues 88-96 of SEQ ID NO:343 (CDR-L3);

residues 31-37 of SEQ ID NO:344 (CDR-H1); residues 52-67 of SEQ ID NO:344 (CDR-H2); residues 100-110 of SEQ ID NO:344 (CDR-H3);

residues 24-34 of SEQ ID NO:345 (CDR-L1); residues 50-56 of SEQ ID NO:345 (CDR-L2); residues 89-97 of SEQ ID NO:345 (CDR-L3);

residues 31-37 of SEQ ID NO:346 (CDR-H1); residues 52-67 of SEQ ID NO:346 (CDR-H2); residues 100-110 of SEQ ID NO:346 (CDR-H3);

residues 23-33 of SEQ ID NO:347 (CDR-L1); residues 49-55 of SEQ ID NO:347 (CDR-L2); residues 88-96 of SEQ ID NO:347 (CDR-L3);

residues 31-37 of SEQ ID NO:348 (CDR-H1); residues 52-67 of SEQ ID NO:348 (CDR-H2); residues 100-110 of SEQ ID NO:348 (CDR-H3);

residues 24-34 of SEQ ID NO:349 (CDR-L1); residues 50-56 of SEQ ID NO:349 (CDR-L2); residues 89-97 of SEQ ID NO:349 (CDR-L3);

residues 31-37 of SEQ ID NO:350 (CDR-H1); residues 52-67 of SEQ ID NO:350 (CDR-H2); residues 100-110 of SEQ ID NO:350 (CDR-H3);

residues 24-34 of SEQ ID NO:351 (CDR-L1); residues 50-56 of SEQ ID NO:351 (CDR-L2); residues 89-97 of SEQ ID NO:351 (CDR-L3);

residues 31-37 of SEQ ID NO:352 (CDR-H1); residues 52-67 of SEQ ID NO:352 (CDR-H2); residues 100-110 of SEQ ID NO:352 (CDR-H3);

residues 24-34 of SEQ ID NO:353 (CDR-L1); residues 50-56 of SEQ ID NO:353 (CDR-L2); residues 89-97 of SEQ ID NO:353 (CDR-L3);

residues 31-37 of SEQ ID NO:354 (CDR-H1); residues 52-67 of SEQ ID NO:354 (CDR-H2); residues 100-110 of SEQ ID NO:354 (CDR-H3);

residues 24-34 of SEQ ID NO:355 (CDR-L1); residues 50-56 of SEQ ID NO:355 (CDR-L2); residues 89-97 of SEQ ID NO:355 (CDR-L3);

residues 31-37 of SEQ ID NO:356 (CDR-H1); residues 52-67 of SEQ ID NO:356 (CDR-H2); residues 100-110 of SEQ ID NO:356 (CDR-H3);

residues 23-33 of SEQ ID NO:357 (CDR-L1); residues 49-55 of SEQ ID NO:357 (CDR-L2); residues 88-96 of SEQ ID NO:357 (CDR-L3);

residues 31-37 of SEQ ID NO:358 (CDR-H1); residues 52-67 of SEQ ID NO:358 (CDR-H2); residues 100-110 of SEQ ID NO:358 (CDR-H3);

residues 23-33 of SEQ ID NO:359 (CDR-L1); residues 49-55 of SEQ ID NO:359 (CDR-L2); residues 88-96 of SEQ ID NO:359 (CDR-L3);

residues 31-37 of SEQ ID NO:360 (CDR-H1); residues 52-67 of SEQ ID NO:360 (CDR-H2); residues 100-110 of SEQ ID NO:360 (CDR-H3);

residues 23-33 of SEQ ID NO:361 (CDR-L1); residues 49-55 of SEQ ID NO:361 (CDR-L2); residues 88-96 of SEQ ID NO:361 (CDR-L3).

3. The binding protein according to claim 1 or claim 2 , wherein said binding protein comprises at least 3 CDRs selected from the group of variable domain CDR sets consisting of:

VH E9 CDR Set

CDR-H1: residues 31-37 of SEQ ID NO:1

CDR-H2: residues 52-67 of SEQ ID NO:1

CDR-H3 residues 100-110 of SEQ ID NO:1

VL E9 CDR Set

CDR-L1: residues 23-33 of SEQ ID NO:111

CDR-L2: residues 49-55 of SEQ ID NO:111

CDR-L3: residues 88-96 of SEQ ID NO:111

VH E9.4 CDR Set

CDR-H1: SEQ ID NO:117

CDR-H2: SEQ ID NO:118

CDR-H3: SEQ ID NO:119

VL E9.4 CDR Set

CDR-L1: SEQ ID NO:229

CDR-L2: SEQ ID NO:230

CDR-L3: SEQ ID NO:231

VH E9.11 CDR Set

CDR-H1: SEQ ID NO:121

CDR-H2: SEQ ID NO:122

CDR-H3: SEQ ID NO:123

VL E9.11 CDR Set

CDR-L1: SEQ ID NO:233

CDR-L2: SEQ ID NO:234

CDR-L3: SEQ ID NO:235

VH E9.14 CDR Set

CDR-H1: SEQ ID NO:125

CDR-H2: SEQ ID NO:126

CDR-H3: SEQ ID NO:127

VL E9.14 CDR Set

CDR-L1: SEQ ID NO:237

CDR-L2: SEQ ID NO:238

CDR-L3: SEQ ID NO:239

VH E9.17 CDR Set

CDR-H1: SEQ ID NO:129

CDR-H2: SEQ ID NO:130

CDR-H3: SEQ ID NO:131

VL E9.17 CDR Set

CDR-L1: SEQ ID NO:241

CDR-L2: SEQ ID NO:242

CDR-L3: SEQ ID NO:243

VH E9.18 CDR Set

CDR-H1: SEQ ID NO:133

CDR-H2: SEQ ID NO:134

CDR-H3: SEQ ID NO:135

VL E9.18 CDR Set

CDR-L1: SEQ ID NO:245

CDR-L2: SEQ ID NO:246

CDR-L3: SEQ ID NO:247

VH E9.19 CDR Set

CDR-H1: SEQ ID NO:137

CDR-H2: SEQ ID NO:138

CDR-H3: SEQ ID NO:139

VL E9.19 CDR Set

CDR-L1: SEQ ID NO:249

CDR-L2: SEQ ID NO:250

CDR-L3: SEQ ID NO:251

VH E9.22 CDR Set

CDR-H1: SEQ ID NO:141

CDR-H2: SEQ ID NO:142

CDR-H3: SEQ ID NO:143

VL E9.22 CDR Set

CDR-L1: SEQ ID NO:253

CDR-L2: SEQ ID NO:254

CDR-L3: SEQ ID NO:255

VH E9.48 CDR Set

CDR-H1: SEQ ID NO:145

CDR-H2: SEQ ID NO:146

CDR-H3: SEQ ID NO:147

VL E9.48 CDR Set

CDR-L1: SEQ ID NO:257

CDR-L2: SEQ ID NO:258

CDR-L3: SEQ ID NO:259

VH E9.65 CDR Set

CDR-H1: SEQ ID NO:149

CDR-H2: SEQ ID NO:150

CDR-H3: SEQ ID NO:151

VL E9.65 CDR Set

CDR-L1: SEQ ID NO:261

CDR-L2: SEQ ID NO:262

CDR-L3: SEQ ID NO:263

VH E9.66 CDR Set

CDR-H1: SEQ ID NO:153

CDR-H2: SEQ ID NO:154

CDR-H3: SEQ ID NO:155

VL E9.66 CDR Set

CDR-L1: SEQ ID NO:265

CDR-L2: SEQ ID NO:266

CDR-L3: SEQ ID NO:267

VH E9.71 CDR Set

CDR-H1: SEQ ID NO:157

CDR-H2: SEQ ID NO:158

CDR-H3: SEQ ID NO:159

VL E9.71 CDR Set

CDR-L1: SEQ ID NO:269

CDR-L2: SEQ ID NO:270

CDR-L3: SEQ ID NO:271

VH E9.13 CDR Set

CDR-H1: SEQ ID NO:161

CDR-H2: SEQ ID NO:162

CDR-H3: SEQ ID NO:163

VL E9.13 CDR Set

CDR-L1: SEQ ID NO:217

CDR-L2: SEQ ID NO:218

CDR-L3: SEQ ID NO:219

VH E9.16 CDR Set

CDR-H1: SEQ ID NO:165

CDR-H2: SEQ ID NO:166

CDR-H3: SEQ ID NO:167

VL E9.16 CDR Set

CDR-L1: SEQ ID NO:221

CDR-L2: SEQ ID NO:222

CDR-L3: SEQ ID NO:223

VH E9.38 CDR Set

CDR-H1: SEQ ID NO:169

CDR-H2: SEQ ID NO:170

CDR-H3: SEQ ID NO:171

VL E9.38 CDR Set

CDR-L1: SEQ ID NO:225

CDR-L2: SEQ ID NO:226

CDR-L3: SEQ ID NO:227

VH E9.2B CDR Set

CDR-H1: SEQ ID NO:173

CDR-H2: SEQ ID NO:174

CDR-H3: SEQ ID NO:175

VL E9.2B CDR Set

CDR-L1: SEQ ID NO:273

CDR-L2: SEQ ID NO:274

CDR-L3: SEQ ID NO:275

VH E9.1F CDR Set

CDR-H1: SEQ ID NO:177

CDR-H2: SEQ ID NO:178

CDR-H3: SEQ ID NO:179

VL E9.1F CDR Set

CDR-L1: SEQ ID NO:277

CDR-L2: SEQ ID NO:278

CDR-L3: SEQ ID NO:279

VH E9.10H CDR Set

CDR-H1: SEQ ID NO:181

CDR-H2: SEQ ID NO:182

CDR-H3: SEQ ID NO:183

VL E9.10H CDR Set

CDR-L1: SEQ ID NO:301

CDR-L2: SEQ ID NO:302

CDR-L3: SEQ ID NO:303

VH E9.5E CDR Set

CDR-H1: SEQ ID NO:185

CDR-H2: SEQ ID NO:186

CDR-H3: SEQ ID NO:187

VL E9.5E CDR Set

CDR-L1: SEQ ID NO:293

CDR-L2: SEQ ID NO:294

CDR-L3: SEQ ID NO:295

VH E9.10C CDR Set

CDR-H1: SEQ ID NO:189

CDR-H2: SEQ ID NO:190

CDR-H3: SEQ ID NO:191

VL E9.10C CDR Set

CDR-L1: SEQ ID NO:281

CDR-L2: SEQ ID NO:282

CDR-L3: SEQ ID NO:283

VH E9.7E CDR Set

CDR-H1: SEQ ID NO:193

CDR-H2: SEQ ID NO:194

CDR-H3: SEQ ID NO:195

VL E9.7E CDR Set

CDR-L1: SEQ ID NO:289

CDR-L2: SEQ ID NO:290

CDR-L3: SEQ ID NO:291

VH E9.12B CDR Set

CDR-H1: SEQ ID NO:197

CDR-H2: SEQ ID NO:198

CDR-H3: SEQ ID NO:199

VL E9.12B CDR Set

CDR-L1: SEQ ID NO:297

CDR-L2: SEQ ID NO:298

CDR-L3: SEQ ID NO:299

VH E9.10E CDR Set

CDR-H1: SEQ ID NO:201

CDR-H2: SEQ ID NO:202

CDR-H3: SEQ ID NO:203

VL E9.10E CDR Set

CDR-L1: SEQ ID NO:285

CDR-L2: SEQ ID NO:286

CDR-L3: SEQ ID NO:287

VH E9.6A CDR Set

CDR-H1: SEQ ID NO:205

CDR-H2: SEQ ID NO:206

CDR-H3: SEQ ID NO:207

VL E9.6A CDR Set

CDR-L1: SEQ ID NO:305

CDR-L2: SEQ ID NO:306

CDR-L3: SEQ ID NO:307

VH E9.7A CDR Set

CDR-H1: SEQ ID NO:209

CDR-H2: SEQ ID NO:210

CDR-H3: SEQ ID NO:211

VL E9.7A CDR Set

CDR-L1: SEQ ID NO:309

CDR-L2: SEQ ID NO:310

CDR-L3: SEQ ID NO:311

VH E9.8H CDR Set

CDR-H1: SEQ ID NO:213

CDR-H2: SEQ ID NO:214

CDR-H3: SEQ ID NO:215

VL E9.8H CDR Set

CDR-L1: SEQ ID NO:313

CDR-L2: SEQ ID NO:314

CDR-L3: SEQ ID NO:315

VH E9.1 CDR Set

CDR-H1: residues 31-37 of SEQ ID NO:334

CDR-H2: residues 52-67 of SEQ ID NO:334

CDR-H3: residues 100-110 of SEQ ID NO:334

VL E9.1 CDR Set

CDR-L1: residues 23-33 of SEQ ID NO:335

CDR-L2: residues 49-55 of SEQ ID NO:335

CDR-L3: residues 88-96 of SEQ ID NO:335

VH E9-SE1 CDR Set

CDR-H1: residues 31-37 of SEQ ID NO:336

CDR-H2: residues 52-67 of SEQ ID NO:336

CDR-H3: residues 100-110 of SEQ ID NO:336

VL E9-SE1 CDR Set

CDR-L1: residues 23-33 of SEQ ID NO:337

CDR-L2: residues 49-55 of SEQ ID NO:337

CDR-L3: residues 88-96 of SEQ ID NO:337

VH E9-SE2 CDR Set

CDR-H1: residues 31-37 of SEQ ID NO:338

CDR-H2: residues 52-67 of SEQ ID NO:338

CDR-H3: residues 100-110 of SEQ ID NO:338

VL E9-SE2 CDR Set

CDR-L1: residues 23-33 of SEQ ID NO:339

CDR-L2: residues 49-55 of SEQ ID NO:339

CDR-L3: residues 88-96 of SEQ ID NO:339

VH E9-SE3 CDR Set

CDR-H1: residues 31-37 of SEQ ID NO:340

CDR-H2: residues 52-67 of SEQ ID NO:340

CDR-H3: residues 100-110 of SEQ ID NO:340

VL E9-SE3 CDR Set

CDR-L1: residues 23-33 of SEQ ID NO:341

CDR-L2: residues 49-55 of SEQ ID NO:341

CDR-L3: residues 88-96 of SEQ ID NO:341

VH E9-SE4 CDR Set

CDR-H1: residues 31-37 of SEQ ID NO:342

CDR-H2: residues 52-67 of SEQ ID NO:342

CDR-H3: residues 100-110 of SEQ ID NO:342

VL E9-SE4 CDR Set

CDR-L1: residues 23-33 of SEQ ID NO:343

CDR-L2: residues 49-55 of SEQ ID NO:343

CDR-L3: residues 88-96 of SEQ ID NO:343

VH E9-SE5 CDR Set

CDR-H1: residues 31-37 of SEQ ID NO:344

CDR-H2: residues 52-67 of SEQ ID NO:344

CDR-H3: residues 100-110 of SEQ ID NO:344

VL E9-SE5 CDR Set

CDR-L1: residues 24-34 of SEQ ID NO:345

CDR-L2: residues 50-56 of SEQ ID NO:345

CDR-L3: residues 89-97 of SEQ ID NO:345

VH E9-SE6 CDR Set

CDR-H1: residues 31-37 of SEQ ID NO:346

CDR-H2: residues 52-67 of SEQ ID NO:346

CDR-H3: residues 100-110 of SEQ ID NO:346

VL E9-SE6 CDR Set

CDR-L1: residues 23-33 of SEQ ID NO:347

CDR-L2: residues 49-55 of SEQ ID NO:347

CDR-L3: residues 88-96 of SEQ ID NO:347

VH E9-SE7 CDR Set

CDR-H1: residues 31-37 of SEQ ID NO:348

CDR-H2: residues 52-67 of SEQ ID NO:348

CDR-H3: residues 100-110 of SEQ ID NO:348

VL E9-SE7 CDR Set

CDR-L1: residues 24-34 of SEQ ID NO:349

CDR-L2: residues 50-56 of SEQ ID NO:349

CDR-L3: residues 89-97 of SEQ ID NO:349

VH E9-SE8 CDR Set

CDR-H1: residues 31-37 of SEQ ID NO:350

CDR-H2: residues 52-67 of SEQ ID NO:350

CDR-H3: residues 100-110 of SEQ ID NO:350

VL E9-SE8 CDR Set

CDR-L1: residues 24-34 of SEQ ID NO:351

CDR-L2: residues 50-56 of SEQ ID NO:351

CDR-L3: residues 89-97 of SEQ ID NO:351

VH E9-FR1 CDR Set

CDR-H1: residues 31-37 of SEQ ID NO:352

CDR-H2: residues 52-67 of SEQ ID NO:352

CDR-H3: residues 100-110 of SEQ ID NO:352

VL E9-FR1 CDR Set

CDR-L1: residues 24-34 of SEQ ID NO:353

CDR-L2: residues 50-56 of SEQ ID NO:353

CDR-L3: residues 89-97 of SEQ ID NO:353

VH E9-FR2 CDR Set

CDR-H1: residues 31-37 of SEQ ID NO:354

CDR-H2: residues 52-67 of SEQ ID NO:354

CDR-H3: residues 100-110 of SEQ ID NO:354

VL E9-FR2 CDR Set

CDR-L1: residues 24-34 of SEQ ID NO:355

CDR-L2: residues 50-56 of SEQ ID NO:355

CDR-L3: residues 89-97 of SEQ ID NO:355

VH E9.71 CDR Set

CDR-H1: residues 31-37 of SEQ ID NO:356

CDR-H2: residues 52-67 of SEQ ID NO:356

CDR-H3: residues 100-110 of SEQ ID NO:356

VL E9.71 CDR Set

CDR-L1: residues 23-33 of SEQ ID NO:357

CDR-L2: residues 49-55 of SEQ ID NO:357

CDR-L3: residues 88-96 of SEQ ID NO:357

VH E9.71(M) CDR Set

CDR-H1: residues 31-37 of SEQ ID NO:358

CDR-H2: residues 52-67 of SEQ ID NO:358

CDR-H3: residues 100-110 of SEQ ID NO:358

VL E9.71(M) CDR Set

CDR-L1: residues 23-33 of SEQ ID NO:359

CDR-L2: residues 49-55 of SEQ ID NO:359

CDR-L3: residues 88-96 of SEQ ID NO:359

VH E9.71(L) CDR Set

CDR-H1: residues 31-37 of SEQ ID NO:360

CDR-H2: residues 52-67 of SEQ ID NO:360

CDR-H3: residues 100-110 of SEQ ID NO:360

VL E9.71(L) CDR Set

CDR-L1: residues 23-33 of SEQ ID NO:361

CDR-L2: residues 49-55 of SEQ ID NO:361

CDR-L3: residues 88-96 of SEQ ID NO:361.

4. The binding protein according to claim 3 , comprising at least two variable domain CDR sets.

5. The binding protein according to claim 4 , wherein said at least two variable domain CDR sets are selected from a group consisting of:

VH E9 CDR Set and VL E9 CDR Set,

VH E9.4 CDR Set and VL E9.4 CDR Set,

VH E9.11 CDR Set and VL E9.11 CDR Set,

VH E9.14 CDR Set and VL E9.14 CDR Set,

VH E9.17 CDR Set and VL E9.17 CDR Set,

VH E9.18 CDR Set and VL E9.18 CDR Set,

VH E9.19 CDR Set and VL E9.19 CDR Set,

VH E9.22 CDR Set and VL E9.22 CDR Set,

VH E9.48 CDR Set and VL E9.48 CDR Set,

VH E9.65 CDR Set and VL E9.65 CDR Set,

VH E9.66 CDR Set and VL E9.66 CDR Set,

VH E9.71 CDR Set and VL E9.71 CDR Set,

VH E9.13 CDR Set and VL E9.13 CDR Set,

VH E9.16 CDR Set and VL E9.16 CDR Set,

VH E9.38 CDR Set and VL E9.38 CDR Set,

VH E9.2B CDR Set and VL E9.2B CDR Set,

VH E9.1F CDR Set and VL E9.1F CDR Set,

VH E9.10H CDR Set and VL E9.10H CDR Set,

VH E9.5E CDR Set and VL E9.5E CDR Set,

VH E9.10C CDR Set and VL E9.10C CDR Set,

VH E9.7E CDR Set and VL E9.7E CDR Set,

VH E9.12B CDR Set and VL E9.12B CDR Set,

VH E9.10E CDR Set and VL E9.10E CDR Set,

VH E9.6A CDR Set and VL E9.6A CDR Set,

VH E9.7A CDR Set and VL E9.7A CDR Set,

VH E9.8H CDR Set and VL E9.8H CDR Set,

VH E9-SE1 CDR Set and VL E9-SE1 CDR Set,

VH E9-SE2 CDR Set and VL E9-SE2 CDR Set,

VH E9-SE3 CDR Set and VL E9-SE3 CDR Set,

VH E9-SE4 CDR Set and VL E9-SE4 CDR Set,

VH E9-SE5 CDR Set and VL E9-SE5 CDR Set,

VH E9-SE6 CDR Set and VL E9-SE6 CDR Set,

VH E9-SE7 CDR Set and VL E9-SE7 CDR Set,

VH E9-SE8 CDR Set and VL E9-SE8 CDR Set,

VH E9-FR1 CDR Set and VL E9-FR1 CDR Set,

VH E9-FR2 CDR Set and VL E9-FR2 CDR Set,

VH E9.71 CDR Set and VL E9.71 CDR Set,

VH E9.71(M) CDR Set and VL E9.71(M) CDR Set, and

VH E9.71(L) CDR Set and VL E9.71(L) CDR Set.

6. The binding protein according to any one of claims 1 - 2 , further comprising a human acceptor framework.

7. The binding protein according to claim 6 , wherein said human acceptor framework comprises an amino acid sequence selected from the group consisting of:

SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19 SEQ ID NO: 20, SEQ ID NO: 21, SEQ ID NO: 22, SEQ ID NO: 35, SEQ ID NO: 36, SEQ ID NO: 37, SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40, SEQ ID NO: 41, SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 45, SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48, SEQ ID NO: 49, SEQ ID NO: 50, SEQ ID NO: 51, SEQ ID NO: 52, SEQ ID NO: 53, SEQ ID NO: 54, SEQ ID NO: 55, SEQ ID NO: 56, SEQ ID NO: 57, SEQ ID NO: 58, SEQ ID NO: 59, SEQ ID NO: 60, SEQ ID NO: 61, SEQ ID NO: 62,

SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25, SEQ ID NO: 26, SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 29, SEQ ID NO: 30, SEQ ID NO: 31, SEQ ID NO: 32, SEQ ID NO: 33, SEQ ID NO: 34, SEQ ID NO: 63, SEQ ID NO: 64, SEQ ID NO: 65, SEQ ID NO: 66, SEQ ID NO: 67, SEQ ID NO: 68, SEQ ID NO: 69, SEQ ID NO: 70, SEQ ID NO: 71, SEQ ID NO: 72, SEQ ID NO: 73, SEQ ID NO: 74, SEQ ID NO: 75, SEQ ID NO: 76, SEQ ID NO: 77, SEQ ID NO: 78, SEQ ID NO: 79, SEQ ID NO: 80, SEQ ID NO: 81, SEQ ID NO: 82, SEQ ID NO: 83, SEQ ID NO: 84, SEQ ID NO: 85, SEQ ID NO: 86, SEQ ID NO: 87, SEQ ID NO: 88, SEQ ID NO: 89, SEQ ID NO: 90, SEQ ID NO: 91, SEQ ID NO: 92, SEQ ID NO: 93, SEQ ID NO: 94, SEQ ID NO: 95, SEQ ID NO: 96, SEQ ID NO: 97, and SEQ ID NO: 98.

8. The binding protein according to claim 7 , wherein said human acceptor framework comprises at least one framework region amino acid substitution at a key residue, said key residue selected from the group consisting of:

a residue adjacent to a CDR;

a glycosylation site residue;

a rare residue;

a residue capable of interacting with human DLL4

a canonical residue;

a contact residue between heavy chain variable region and light chain variable region;

a residue within a Vernier zone; and

a residue in a region that overlaps between a Chothia-defined variable heavy chain CDR1 and a Kabat-defined first heavy chain framework.

9. The binding protein according to claim 8 , wherein said key residue is selected from the group consisting of: 2H, 4H, 24H, 26H, 27H, 29H, 34H, 35H, 37H, 39H, 44H, 45H, 47H, 48H, 49H, 50H, 51H, 58H, 59H, 60H, 63H, 67H, 69H, 71H, 73H, 76H, 78H, 91H, 93H, 94H, 2L, 4L, 25L, 29L, 27bL, 33L, 34L, 36L, 38L, 43L, 44L, 46L, 47L, 48L, 49L, 55L, 58L, 62L, 64L, 71L, 87L, 89L, 90L, 91L, 94L, and 95L.

10. The binding protein according to claim 1 , wherein said binding protein comprises at least one variable domain having amino acid sequence selected from the group consisting of:

SEQ ID NOS:1, 111, 116, 228, 120, 232, 124, 236, 128, 240, 132, 244, 136, 248, 140, 252, 144, 256, 148, 260, 152, 264, 156, 268, 160, 216, 164, 220, 168, 224, 172, 272, 176, 276, 180, 300, 184, 292, 188, 280, 192, 288, 196, 296, 200, 284, 204, 304, 208, 308, 212, 312, 334, 335, 336, 337, 338, 339, 340, 341, 342, 343, 344, 345, 346, 347, 348, 349, 350, 351, 352, 353, 354, 355, 356, 357, 358, 359, 360, and 361.

11. The binding protein according to claim 10 , wherein said binding protein comprises two variable domains, wherein said two variable domains have amino acid sequences selected from the group consisting of: SEQ ID NOS:1 and 111, SEQ ID NOS:116 and 228, SEQ ID NOS:120 and 232, SEQ ID NOS:124 and 236, SEQ ID NOS:128 and 240, SEQ ID NOS:132 and 244, SEQ ID NOS:136 and 248, SEQ ID NOS:140 and 252, SEQ ID NOS:144 and 256, SEQ ID NOS:148 and 260, SEQ ID NOS:152 and 264, SEQ ID NOS:156 and 268, SEQ ID NOS: 160 and 216, SEQ ID NOS: 164 and 220, SEQ ID NOS:168 and 224, SEQ ID NOS:172 and 272, SEQ ID NOS:176 and 276, SEQ ID NOS:180 and 300, SEQ ID NOS:184 and 292, SEQ ID NOS:188 and 280, SEQ ID NOS:192 and 288, SEQ ID NOS:196 and 296, SEQ ID NOS:200 and 284, SEQ ID NOS:204 and 304, SEQ ID NOS:208 and 308, SEQ ID NOS:212 and 312, SEQ ID NOS:334 and 335, SEQ ID NOS:336 and 337, SEQ ID NOS:338 and 339, SEQ ID NOS:340 and 341, SEQ ID NOS:342 and 343, SEQ ID NOS:344 and 345, SEQ ID NOS:346 and 347, SEQ ID NOS:348 and 349, SEQ ID NOS:350 and 351, SEQ ID NOS:352 and 353, SEQ ID NOS:354 and 355, SEQ ID NOS:356 and 357, SEQ ID NOS:358 and 359, SEQ ID NOS:360 and 361.

12. The binding protein according to claim 9 , wherein said binding protein comprises at least one variable domain having an amino acid sequence selected from the group consisting of: SEQ ID NOS:1, 111, 116, 228, 120, 232, 124, 236, 128, 240, 132, 244, 136, 248, 140, 252, 144, 256, 148, 260, 152, 264, 156, 268, 160, 216, 164, 220, 168, 224, 172, 272, 176, 276, 180, 300, 184, 292, 188, 280, 192, 288, 196, 296, 200, 284, 204, 304, 208, 308, 212, 312, 334, 335, 336, 337, 338, 339, 340, 341, 342, 343, 344, 345, 346, 347, 348, 349, 350, 351, 352, 353, 354, 355, 356, 357, 358, 359, 360, and 361.

13. The binding protein according to claim 12 , further comprising a heavy chain immunoglobulin constant domain selected from the group consisting of: a human IgM constant domain; a human IgG1 constant domain; a human IgG2 constant domain; a human IgG3 constant domain; a human IgG4 constant domain; a human IgE constant domain and a human IgA constant domain.

14. The binding protein according to claim 13 wherein said heavy chain immunoglobulin constant domain is a human IgG1 constant domain, said human IgG1 constant domain comprising amino acid sequence selected from the group consisting of SEQ ID NO:2 and SEQ ID NO:3.

15. The binding protein according to claim 1 , further comprising a light chain immunoglobulin constant domain, wherein said light chain immunoglobulin constant domain is a human Ig kappa constant domain comprising amino acid sequence SEQ ID NO:4.

16. The binding protein according to claim 1 , further comprising a light chain immunoglobulin constant domain, wherein said light chain immunoglobulin constant region domain is a human Ig lambda constant domain comprising amino acid sequence SEQ ID NO:5.

17. The binding protein according to claim 1 wherein said binding protein is selected from the group consisting of: an immunoglobulin molecule, an scFv, a monoclonal antibody, a human antibody, a chimeric antibody, a humanized antibody, a single domain antibody, a Fab fragment, a Fab′ fragment, an F(ab′) 2 , an Fv, a disulfide linked Fv, a single domain antibody, a diabody, a multispecific antibody, a bispecific antibody, and a dual specific antibody.

18. The binding protein according to claim 17 wherein said binding protein is a human antibody.

19. A binding protein capable of binding human DLL-4, said binding protein comprising:

an Ig constant heavy region having an amino acid sequence selected from the group consisting of SEQ ID NO:2 and SEQ ID NO:3;

an Ig constant light region having an amino acid sequence selected from the group consisting of SEQ ID NO:4 and SEQ ID NO:5;

an Ig variable heavy region having an amino acid sequence selected from the group consisting:

SEQ ID NOS:1, 116, 120, 124, 128, 132, 136, 140, 144, 148, 152, 156, 160, 164, 168, 172, 176, 180, 184, 188, 192, 196, 200, 204, 208, 212, 334, 336, 338, 340, 342, 344, 346, 348, 350, 352, 354, 356, 358, and 360; and

an Ig variable light region having an amino acid sequence selected from the group consisting:

SEQ ID NOS:111, 228, 232, 236, 240, 244, 248, 252, 256, 260, 264, 268, 216, 220, 224, 272, 276, 300, 292, 280, 288, 296, 284, 304, 308, 312, 335, 337, 339, 341, 343, 345, 347, 349, 351, 353, 355, 357, 359, and 361.

20. The binding protein according to claim 19 , wherein the Ig constant light region is SEQ ID NO:5.

21. The binding protein according to any one of claims 1 - 2 , 10 - 11 , 13 , 14 , and 15 - 20 , wherein the binding protein is capable of blocking DLL4 interaction with a Notch protein selected from the group consisting of Notch-1, Notch-2, Notch-3, Notch-4, and combinations thereof.

22. The binding protein according to claim 21 , wherein the binding protein is capable of blocking DLL4 interaction with Notch-1 and Notch-4.

23. The binding protein according to any one of claims 1 - 2 , 10 - 11 , 13 , 14 , and 15 - 20 , wherein the binding protein is capable of modulating a biological function of DLL4.

24. The binding protein according to any one of claims 1 - 2 , 10 - 11 , 13 , 14 , and 15 - 20 , wherein said binding protein is capable of neutralizing a DLL4.

25. The neutralizing binding protein according to claim 24 wherein said DLL4 is selected from the group consisting of: human DLL4, mouse DLL4, cynomolgus DLL4, and rat DLL4.

26. The binding protein according to claim 24 wherein said binding protein is capable of reducing normal angiogenesis.

27. The neutralizing binding protein according to claim 24 , wherein said neutralizing binding protein has a dissociation constant (K D ) selected from the group consisting of: at most about 10 −7 M; at most about 10 −8 M; at most about 10 −9 M; at most about 10 −10 M; at most about 10 −11 M; at most about 10 −12 M; and at most 10 −13 M.

28. The neutralizing binding protein according to claim 24 , wherein said neutralizing binding protein has an on rate selected from the group consisting of: at least about 10 2 M −1 s −1 ; at least about 10 3 M −1 s −1 ; at least about 10 4 M −1 s −1 ; at least about 10 5 M −1 s −1 ; and at least about 10 6 M −1 s −1 .

29. The neutralizing binding protein according to claim 24 , wherein said neutralizing binding protein has an off rate selected from the group consisting of: at most about 10 −3 s −1 ; at most about 10 −4 s −1 ; at most about 10 −5 s −1 ; and at most about 10 6 s −1 .

30. A labeled binding protein comprising a binding protein of claim 17 , wherein said binding protein is conjugated to a detectable label.

31. An antibody construct comprising a binding protein described in claim 1 and further comprising a linker polypeptide or an immunoglobulin constant domain.

32. The antibody construct according to claim 31 , selected from the group consisting of:

an immunoglobulin molecules,

a monoclonal antibody,

a chimeric antibody,

a CDR-grafted antibody,

a humanized antibody,

a Fab,

a Fab′,

a F(ab′) 2 ,

a Fv,

a disulfide linked Fv,

a scFv,

a single domain antibody,

a diabody,

a multispecific antibody,

a dual specific antibody, and

a bispecific antibody.

33. The antibody construct according to claim 31 , wherein said antibody construct comprises a heavy chain immunoglobulin constant domain selected from the group consisting of:

a human IgM constant domain,

a human IgG1 constant domain,

a human IgG2 constant domain,

a human IgG3 constant domain,

a human IgG4 constant domain,

a human IgE constant domain,

a human IgA constant domain,

and an IgG constant domain variant with one or more mutations altering binding strength to Fc neonatal receptor, Fc gamma receptors, or C1q.

34. An antibody conjugate comprising an antibody construct as described in claim 31 , wherein said antibody construct is conjugated to a therapeutic or cytotoxic agent.

35. The antibody conjugate of claim 34 , wherein said therapeutic or cytotoxic agent is selected from the group consisting of: an anti-metabolite, an alkylating agent, an antibiotic, a growth factor, a cytokine, an anti-angiogenic agent, an anti-mitotic agent, an anthracycline, toxin, and an apoptotic agent.

36. A pharmaceutical composition comprising the binding protein of claim 1 , and a pharmaceutically acceptable carrier.

37. The pharmaceutical composition of claim 36 further comprising at least one additional therapeutic agent for treating a disorder in which DLL4 activity is detrimental.

38. The pharmaceutical composition of claim 37 , wherein said additional agent is selected from the group consisting of: angiogenesis inhibitors; kinase inhibitors; co-stimulation molecule blockers; adhesion molecule blockers; anti-cytokine antibody or functional fragment thereof; methotrexate; corticosteroids; cyclosporine; rapamycin; FK506; and non-steroidal anti-inflammatory agents.

39. A binding protein capable of binding human DLL4, wherein said binding protein comprises an antibody or an antigen binding fragment thereof, said antibody or antigen binding fragment comprising:

a variable heavy chain domain comprising the amino acid sequence of SEQ ID NO: 156, and

a variable light chain domain comprising the amino acid sequence of SEQ ID NO 268.

40. The binding protein of claim 39 , further comprising a heavy chain immunoglobulin constant domain comprising an amino acid sequence selected from the group consisting of SEQ ID NO:2 and SEQ ID NO:3, and

a light chain immunoglobulin constant domain comprising an amino acid sequence selected from the group consisting of SEQ ID NO 4 and SEQ ID NO: 5.

41. A binding protein capable of binding human DLL4, wherein said binding protein comprises an antibody or an antigen binding fragment thereof, said antibody or antigen binding fragment comprising:

a variable heavy chain domain comprising the amino acid sequence of SEQ ID NO: 360, and

a variable light chain domain comprising the amino acid sequence of SEQ ID NO 361.

42. The binding protein of claim 41 , further comprising a heavy chain immunoglobulin constant domain comprising an amino acid sequence selected from the group consisting of SEQ ID NO:2 and SEQ ID NO:3, and

a light chain immunoglobulin constant domain comprising an amino acid sequence selected from the group consisting of SEQ ID NO 4 and SEQ ID NO: 5.

43. A binding protein capable of binding human DLL4, wherein said binding protein comprises an antibody or an antigen binding fragment thereof, said antibody or antigen binding fragment comprising:

a variable heavy chain domain comprising the amino acid sequence of SEQ ID NO: 156, and

a variable light chain domain comprising the amino acid sequence of SEQ ID NO 359.

44. The binding protein of claim 43 , further comprising a heavy chain immunoglobulin constant domain comprising an amino acid sequence selected from the group consisting of SEQ ID NO:2 and SEQ ID NO:3, and

a light chain immunoglobulin constant domain comprising an amino acid sequence selected from the group consisting of SEQ ID NO 4 and SEQ ID NO: 5.