Novel heterodimeric proteins
AssigneeXencor, Inc.
InventorsGregory Moore, Matthew Bernett, Rumana Rashid, John Desjarlais
Life of this patent
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Abstract
The invention provides novel heterodimeric proteins including heterodimeric antibodies.
Claims81
A composition comprising an anti-CD3 variable region having a sequence comprising a vhCDR1 having SEQ ID NO:411, a vhCDR2 having SEQ ID NO:413, a vhCDR3 having SEQ ID NO:416, a vlCDR1 having SEQ ID NO:420, a vlCDR2 having SEQ ID NO:425 and a vlCDR3 having SEQ ID NO:430.
A composition comprising an anti-CD3 variable region having a sequence comprising a vhCDR1 having the sequence T-Y-A-M-Xaa1, wherein Xaa1 is N, S or H (SEQ ID NO:435), a vhCDR2 having the sequence R-I-R-S-K-Xaa1-N-Xaa2-Y-A-T-Xaa3-Y-Y-A-Xaa4-S-V-K-G, wherein Xaa1 is Y or A, Xaa2 is N or S, Xaa3 is Y or A and Xaa4 is D or A (SEQ ID NO:436), a vhCDR3 having the sequence H-G-N-F-G-Xaa1-S-Y-V-S-W-F-Xaa2-Y, wherein Xaa1 is N, D or Q and Xaa2 is A or D (SEQ ID NO:437), a vlCDR1 having the sequence Xaa1-S-S-T-G-A-V-T-Xaa2-Xaa3-Xaa4-Y-A-N, wherein Xaa1 is G, R or K, Xaa2 is T or S, Xaa3 is S or G and Xaa4 is N or H, (SEQ ID NO:438), a vlCDR2 having the sequence Xaa1-T-N-Xaa2-R-A-Xaa3, wherein Xaa1 is G or D, Xaa2 is K or N, and Xaa3 is P or S (SEQ ID NO:439) and a vlCDR3 having the sequence Xaa1-L-W-Y-S-N-Xaa2-W-V, wherein Xaa1 is A or L and Xaa2 is L or H (SEQ ID NO:440).
A nucleic acid composition encoding an anti-CD3 variable region comprising a variable heavy region and a variable light region selected from the group consisting of SEQ ID NOs:
- 5 and 6;
- SEQ ID NOs:
- 9 and 10;
- SEQ ID NOs:
- 13 and 14;
- SEQ ID NOs:
- 17 and 18;
- SEQ ID NOs:
- 21 and 22;
- SEQ ID NOs:
- 25 and 26;
- SEQ ID NOs:
- 29 and 30;
- SEQ ID NOs:
- 33 and 34;
- SEQ ID NOs:
- 37 and 38;
- SEQ ID NOs:
- 41 and 42;
- SEQ ID NOs:
- 45 and 46;
- SEQ ID NOs:
- 49 and 50;
- SEQ ID NOs:
- 53 and 54;
- SEQ ID NOs:
- 57 and 58;
- SEQ ID NOs:
- 61 and 62;
- SEQ ID NOs:
- 65 and 66;
- SEQ ID NOs:
- 69 and 70;
- SEQ ID NOs:
- 73 and 74;
- SEQ ID NOs:
- 77 and 78;
- SEQ ID NOs:
- 81 and 82;
- SEQ ID NOs:
- 85 and 86;
- SEQ ID NOs:
- 89 and 90;
- SEQ ID NOs:
- 93 and 94;
- SEQ ID NOs:
- 97 and 98;
- SEQ ID NOs:
- 101 and 102;
- SEQ ID NOs:
- 105 and 106;
- SEQ ID NOs:
- 109 and 110;
- SEQ ID NOs:
- 113 and 114;
- SEQ ID NOs:
- 117 and 118;
- SEQ ID NOs:
- 121 and 122;
- SEQ ID NOs:
- 125 and 126;
- SEQ ID NOs:
- 129 and 130;
- SEQ ID NOs:
- 133 and 134;
- SEQ ID NOs:
- 137 and 138;
- SEQ ID NOs:
- 141 and 142;
- SEQ ID NOs:
- 145 and 146;
- SEQ ID NOs:
- 149 and 150;
- SEQ ID NOs:
- 153 and 154;
- SEQ ID NOs:
- 157 and 158;
- SEQ ID NOs:
- 161 and 162;
- SEQ ID NOs:
- 165 and 166;
- SEQ ID NOs:
- 169 and 170;
- SEQ ID NOs:
- 173 and 174;
- SEQ ID NOs:
- 177 and 178;
- SEQ ID NOs:
- 181 and 182;
- SEQ ID NOs:
- 185 and 186;
- SEQ ID NOs:
- 189 and 190;
- SEQ ID NOs:
- 193 and 194;
- SEQ ID NOs:
- 197 and 198;
- SEQ ID NOs:
- 201 and 202;
- SEQ ID NOs:
- 205 and 206;
- SEQ ID NOs:
- 209 and 210;
- SEQ ID NOs:
- 213 and 214;
- SEQ ID NOs:
- 217 and 218;
- SEQ ID NOs:
- 221 and 222;
- SEQ ID NOs:
- 225 and 226;
- SEQ ID NOs:
- 229 and 230;
- SEQ ID NOs:
- 233 and 234;
- SEQ ID NOs:
- 237 and 238;
- SEQ ID NOs:
- 241 and 242;
- SEQ ID NOs:
- 245 and 246;
- SEQ ID NOs:
- 249 and 250;
- SEQ ID NOs:
- 253 and 254;
- SEQ ID NOs:
- 257 and 258;
- SEQ ID NOs:
- 261 and 262;
- SEQ ID NOs:
- 265 and 266;
- SEQ ID NOs:
- 269 and 270;
- SEQ ID NOs:
- 273 and 274;
- SEQ ID NOs:
- 277 and 278;
- SEQ ID NOs:
- 281 and 282;
- SEQ ID NOs:
- 285 and 286;
- SEQ ID NOs:
- 289 and 290;
- SEQ ID NOs:
- 293 and 294;
- SEQ ID NOs:
- 297 and 298;
- SEQ ID NOs:
- 301 and 302;
- SEQ ID NOs:
- 305 and 306;
- SEQ ID NOs:
- 309 and 310;
- SEQ ID NOs:
- 313 and 314;
- SEQ ID NOs:
- 317 and 318;
- SEQ ID NOs:
- 321 and 322;
- SEQ ID NOs:
- 325 and 326;
- SEQ ID NOs:
- 329 and 330;
- SEQ ID NOs:
- 333 and 334;
- SEQ ID NOs:
- 337 and 338;
- SEQ ID NOs:
- 341 and 342;
- SEQ ID NOs:
- 345 and 346;
- SEQ ID NOs:
- 349 and 350;
- SEQ ID NOs:
- 353 and 354;
- SEQ ID NOs:
- 357 and 358;
- SEQ ID NOs:
- 361 and 362;
- SEQ ID NOs:
- 365 and 366;
- SEQ ID NOs:
- 369 and 370;
- SEQ ID NOs:
- 373 and 374;
- SEQ ID NOs:
- 377 and 378;
- SEQ ID NOs:
- 381 and 382;
- SEQ ID NOs:
- 385 and 386;
- SEQ ID NOs:
- 389 and 390;
- SEQ ID NOs:
- 393 and 394;
- SEQ ID NOs:
- 397 and 398;
- SEQ ID NOs:
- 401 and 402;
- SEQ ID NOs:
- 405 and 406;
- SEQ ID NOs:
- 409 and 410
A method of making a composition comprising an anti-CD3 variable region comprising culturing a host cell according to claim A18 under conditions wherein said composition is expressed.
A heterodimeric antibody comprising:
- a) a first heavy chain comprising:
- i) a first Fc domain;
- and
- ii) a single chain Fv region (scFv) that binds CD3 comprising aa vhCDR1 having the sequence T-Y-A-M-Xaa1, wherein Xaa1 is N, S or H (SEQ ID NO:435), a vhCDR2 having the sequence R-I-R-S-K-Xaa1-N-Xaa2-Y-A-T-Xaa3-Y-Y-A-Xaa4-S-V-K-G, wherein Xaa1 is Y or A, Xaa2 is N or S, Xaa3 is Y or A and Xaa4 is D or A (SEQ ID NO:436), a vhCDR3 having the sequence H-G-N-F-G-Xaa1-S-Y-V-S-W-F-Xaa2-Y, wherein Xaa1 is N, D or Q and Xaa2 is A or D (SEQ ID NO:437), a vlCDR1 having the sequence Xaa1-S-S-T-G-A-V-T-Xaa2-Xaa3-Xaa4-Y-A-N, wherein Xaa1 is G, R or K, Xaa2 is T or S, Xaa3 is S or G and Xaa4 is N or H, (SEQ ID NO:438), a vlCDR2 having the sequence Xaa1-T-N-Xaa2-R-A-Xaa3, wherein Xaa1 is G or D, Xaa2 is K or N, and Xaa3 is P or S (SEQ ID NO:439) and a vlCDR3 having the sequence Xaa1-L-W-Y-S-N-Xaa2-W-V, wherein Xaa1 is A or L and Xaa2 is L or H (SEQ ID NO:440);
- and
- b) a second heavy chain comprising:
- i) a second Fc domain;
- ii) a first variable heavy chain;
- and
- ii) a first variable light chain;
- wherein said first and second Fc domains are different.
A nucleic acid composition encoding a heterodimeric antibody comprising a variable heavy region and a variable light region selected from the group consisting of SEQ ID NOs:
- 5 and 6;
- SEQ ID NOs:
- 9 and 10;
- SEQ ID NOs:
- 13 and 14;
- SEQ ID NOs:
- 17 and 18;
- SEQ ID NOs:
- 21 and 22;
- SEQ ID NOs:
- 25 and 26;
- SEQ ID NOs:
- 29 and 30;
- SEQ ID NOs:
- 33 and 34;
- SEQ ID NOs:
- 37 and 38;
- SEQ ID NOs:
- 41 and 42;
- SEQ ID NOs:
- 45 and 46;
- SEQ ID NOs:
- 49 and 50;
- SEQ ID NOs:
- 53 and 54;
- SEQ ID NOs:
- 57 and 58;
- SEQ ID NOs:
- 61 and 62;
- SEQ ID NOs:
- 65 and 66;
- SEQ ID NOs:
- 69 and 70;
- SEQ ID NOs:
- 73 and 74;
- SEQ ID NOs:
- 77 and 78;
- SEQ ID NOs:
- 81 and 82;
- SEQ ID NOs:
- 85 and 86;
- SEQ ID NOs:
- 89 and 90;
- SEQ ID NOs:
- 93 and 94;
- SEQ ID NOs:
- 97 and 98;
- SEQ ID NOs:
- 101 and 102;
- SEQ ID NOs:
- 105 and 106;
- SEQ ID NOs:
- 109 and 110;
- SEQ ID NOs:
- 113 and 114;
- SEQ ID NOs:
- 117 and 118;
- SEQ ID NOs:
- 121 and 122;
- SEQ ID NOs:
- 125 and 126;
- SEQ ID NOs:
- 129 and 130;
- SEQ ID NOs:
- 133 and 134;
- SEQ ID NOs:
- 137 and 138;
- SEQ ID NOs:
- 141 and 142;
- SEQ ID NOs:
- 145 and 146;
- SEQ ID NOs:
- 149 and 150;
- SEQ ID NOs:
- 153 and 154;
- SEQ ID NOs:
- 157 and 158;
- SEQ ID NOs:
- 161 and 162;
- SEQ ID NOs:
- 165 and 166;
- SEQ ID NOs:
- 169 and 170;
- SEQ ID NOs:
- 173 and 174;
- SEQ ID NOs:
- 177 and 178;
- SEQ ID NOs:
- 181 and 182;
- SEQ ID NOs:
- 185 and 186;
- SEQ ID NOs:
- 189 and 190;
- SEQ ID NOs:
- 193 and 194;
- SEQ ID NOs:
- 197 and 198;
- SEQ ID NOs:
- 201 and 202;
- SEQ ID NOs:
- 205 and 206;
- SEQ ID NOs:
- 209 and 210;
- SEQ ID NOs:
- 213 and 214;
- SEQ ID NOs:
- 217 and 218;
- SEQ ID NOs:
- 221 and 222;
- SEQ ID NOs:
- 225 and 226;
- SEQ ID NOs:
- 229 and 230;
- SEQ ID NOs:
- 233 and 234;
- SEQ ID NOs:
- 237 and 238;
- SEQ ID NOs:
- 241 and 242;
- SEQ ID NOs:
- 245 and 246;
- SEQ ID NOs:
- 249 and 250;
- SEQ ID NOs:
- 253 and 254;
- SEQ ID NOs:
- 257 and 258;
- SEQ ID NOs:
- 261 and 262;
- SEQ ID NOs:
- 265 and 266;
- SEQ ID NOs:
- 269 and 270;
- SEQ ID NOs:
- 273 and 274;
- SEQ ID NOs:
- 277 and 278;
- SEQ ID NOs:
- 281 and 282;
- SEQ ID NOs:
- 285 and 286;
- SEQ ID NOs:
- 289 and 290;
- SEQ ID NOs:
- 293 and 294;
- SEQ ID NOs:
- 297 and 298;
- SEQ ID NOs:
- 301 and 302;
- SEQ ID NOs:
- 305 and 306;
- SEQ ID NOs:
- 309 and 310;
- SEQ ID NOs:
- 313 and 314;
- SEQ ID NOs:
- 317 and 318;
- SEQ ID NOs:
- 321 and 322;
- SEQ ID NOs:
- 325 and 326;
- SEQ ID NOs:
- 329 and 330;
- SEQ ID NOs:
- 333 and 334;
- SEQ ID NOs:
- 337 and 338;
- SEQ ID NOs:
- 341 and 342;
- SEQ ID NOs:
- 345 and 346;
- SEQ ID NOs:
- 349 and 350;
- SEQ ID NOs:
- 353 and 354;
- SEQ ID NOs:
- 357 and 358;
- SEQ ID NOs:
- 361 and 362;
- SEQ ID NOs:
- 365 and 366;
- SEQ ID NOs:
- 369 and 370;
- SEQ ID NOs:
- 373 and 374;
- SEQ ID NOs:
- 377 and 378;
- SEQ ID NOs:
- 381 and 382;
- SEQ ID NOs:
- 385 and 386;
- SEQ ID NOs:
- 389 and 390;
- SEQ ID NOs:
- 393 and 394;
- SEQ ID NOs:
- 397 and 398;
- SEQ ID NOs:
- 401 and 402;
- SEQ ID NOs:
- 405 and 406;
- SEQ ID NOs:
- 409 and 410
A heterodimeric antibody comprising:
- a) a first heavy chain comprising:
- i) a first Fc domain;
- and
- ii) a single chain Fv region (scFv) that binds a first antigen;
- wherein said scFv comprises a charged scFv linker;
- and
- b) a second heavy chain comprising:
- i) a second Fc domain;
- ii) a first variable heavy chain;
- and
- ii) a first variable light chain.
A heterodimeric antibody comprising:
- a) a first heavy chain comprising:
- i) a first Fc domain;
- and
- ii) a single chain Fv region (scFv) that binds a first antigen;
- and
- b) a second heavy chain comprising:
- i) a second Fc domain;
- ii) a first variable heavy chain;
- and
- ii) a first variable light chain;
- wherein said first and second Fc domains comprise a variant set selected from the variants listed in FIG. 9.
A host cell comprising the nucleic acid composition of 57.
A heterodimeric antibody comprising:
- a) a first heavy chain comprising:
- i) a first Fc domain;
- and
- ii) a single chain Fv region (scFv) that binds a first antigen;
- and
- b) a second heavy chain comprising:
- i) a second Fc domain;
- ii) a first variable heavy chain;
- and
- ii) a first variable light chain;
- wherein one of said first and second Fc domains comprises an Fcγ receptor ablation variant set.
A heterodimeric antibody comprising:
- a) a first heavy chain comprising:
- i) a first Fc domain;
- and
- ii) a single chain Fv region that binds a first antigen;
- and
- b) a second heavy chain comprising:
- i) a second Fc domain;
- ii) a first variable heavy chain;
- and
- iii) a first variable light chain;
- wherein said first and second Fc domains comprise a set of variants as shown in Figures, 9, 32 or 33.
A heterodimeric antibody comprising:
- a) a first heavy chain comprising:
- i) a first Fc domain;
- and
- ii) a first single chain Fv region (scFv) that binds a first antigen;
- wherein said first scFv comprises a first charged scFv linker;
- and
- b) a second heavy chain comprising:
- i) a second Fc domain;
- ii) a second scFv that binds a second antigen.
A heterodimeric antibody according to any of 72 to 76 wherein one of said scFvs binds to CD3.
A method of making a heterodimeric antibody comprising:
- a) providing a first nucleic acid encoding a first heavy chain comprising:
- i) a first heavy chain comprising:
- 1 a first Fc domain;
- and
- 2 a single chain Fv region (scFv) that binds a first antigen;
- wherein said scFv comprises a charged linker;
- and
- b) providing a second nucleic acid encoding a second heavy chain comprising:
- i) a second Fc domain;
- ii) a first variable heavy chain;
- and
- c) providing a third nucleic acid comprising a light chain;
- d) expressing said first, second and third nucleic acids in a host cell to produce a first, second and third amino acid sequence, respectively;
- e) loading said first, second and third amino acid sequences onto an ion exchange column;
- and
- f) collecting the heterodimeric fraction.
Dependencies are inferred from the claim text.