ANTIBODIES TARGETING CD32b AND METHODS OF USE THEREOF

• US 20170198040A1
• Filed: 12/16/2016
• Published: 07/13/2017
• Est. Priority Date: 12/18/2015
• Status: Abandoned Application

• Current Assignee: Novartis Ag
• Original Assignee: Novartis Ag
• Inventors: BALKE, Nicole, CALZASCIA, Thomas, EWERT, Stefan, HARRIS, Alan, HUET, Heather Adkins, ISNARDI, Isabelle, LU, Haihui, MEYER, Matthew John, WILSON, Nicholas, WU, Fangmin
• Application Number:
  US15/382,251
• Publication Number:
  US 20170198040A1
• Time in Patent Office: Days
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61K 2039/507 Comprising a combination of two or more separate antibodies
• CPC Class Codes: A61K 2039/541 Mucosal route
• CPC Class Codes: A61K 2039/545 characterised by the dose, timing or administration schedule
• CPC Class Codes: A61K 39/395 Antibodies agglutinins A61K38/36 ; as drug carriers A61K47/50; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/02 specific for leukemia
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07K 16/28 against receptors, cell surface antigens or cell surface determinants
• CPC Class Codes: C07K 16/2803 against the immunoglobulin superfamily
• CPC Class Codes: C07K 16/283 against Fc-receptors, e.g. CD16, CD32, CD64 CD23 C07K16/2851
• CPC Class Codes: C07K 16/2887 against CD20
• CPC Class Codes: C07K 2317/31 multispecific
• CPC Class Codes: C07K 2317/33 Crossreactivity, e.g. for species or epitope, or lack of said crossreactivity
• CPC Class Codes: C07K 2317/34 Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues
• CPC Class Codes: C07K 2317/35 Valency
• CPC Class Codes: C07K 2317/41 Glycosylation, sialylation, or fucosylation
• CPC Class Codes: C07K 2317/56 variable (Fv) region, i.e. VH and/or VL
• CPC Class Codes: C07K 2317/565 Complementarity determining region [CDR]
• CPC Class Codes: C07K 2317/71 : Decreased effector function due to an Fc-modification
• CPC Class Codes: C07K 2317/72 : Increased effector function due to an Fc-modification
• CPC Class Codes: C07K 2317/732 : Antibody-dependent cellular cytotoxicity [ADCC]
• CPC Class Codes: C07K 2317/76 : Antagonist effect on antigen, e.g. neutralization or inhibition of binding
• CPC Class Codes: C07K 2317/92 : Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value

Abstract

The present invention relates to isolated antibodies and antigen-binding fragments thereof which selectively bind human CD32b. Also provided herein are compositions comprising the antibodies or antigen-binding fragments thereof, methods of using the antibodies or antigen-binding fragments thereof, and methods of making the antibodies or antigen-binding fragments thereof.

Claims

1. An isolated antibody or antigen-binding fragment thereof, which comprises:

(a) A heavy chain variable region CDR1 comprising an amino acid sequence selected from any one of SEQ ID NOs;

1, 4, 7, 53, 56, 59, 105, 108, 111, 157, 160, 163, 209, 212, 215, 261, 264, 267, 313, 316, 319, 365, 368, 371, 417, 420, 423, 469, 472, 475, 521, 524, 527, 547, 550, 553, 573, 576, 579, 625, 628, and 631;

(b) a heavy chain variable region CDR2 comprising an amino acid sequence selected from any of SEQ ID NOs;

2, 5, 8, 54, 57, 60, 106, 109, 112, 158, 161, 164, 210, 213, 216, 262, 265, 268, 314, 317, 320, 366, 369, 372, 418, 421;

424, 470, 473, 476, 522, 525, 528, 548, 551, 554, 574, 577, 580, 626, 629, and 632;

(c) a heavy chain variable region CDR3 comprising an amino acid sequence selected from any of SEQ ID NOs;

3, 6, 9, 55, 58, 61, 107, 110, 113, 159, 162, 165, 211, 214, 217, 263, 266, 269, 315, 318, 321, 367, 370, 373, 419, 422, 425, 471, 474, 477, 523, 526, 529, 549, 552, 555, 575, 578, 581, 627, 630, and 633;

(d) a light chain variable region CDR1 comprising an amino acid sequence selected from any of SEQ ID NOs;

14, 17, 20, 66, 69, 72, 118, 121, 124, 170, 173, 176, 222, 225, 228, 274, 277, 280, 326, 329, 332, 378, 381, 384, 430, 433, 436, 482, 485, 488, 534, 537, 540, 560, 563, 566, 586, 589, 592, 638, 641, 644;

(e) a light chain variable region CDR2 comprising an amino acid sequence selected from any of SEQ ID NOs;

15, 18, 21, 67, 70, 73, 119, 122, 125, 171, 174, 177, 223, 226, 229, 275, 278, 281, 327, 330, 333, 379, 382, 385, 431, 434, 437, 483, 486, 489, 535, 538, 541, 561, 564, 567, 587, 590, 593, 639, 642, and 645; and

(f) a light chain variable region CDR3 comprising an amino acid sequence selected from any of SEQ ID NOs;

16, 19, 22, 68, 71, 74, 120, 123, 126, 172, 175, 178, 224, 227, 230, 276, 279, 282, 328, 331, 334, 380, 383, 386, 432, 435, 438, 484, 487, 490, 536, 539, 542, 562, 565, 568, 588, 591, 594, 640, 643, and 646;

wherein the antibody selectively binds human CD32b.

2. The antibody or antigen-binding fragment thereof of claim 1, wherein the antibody comprises:

a heavy chain variable region comprising an amino acid sequence selected from any of SEQ ID NOs;

10, 62, 114, 166, 218, 270, 322, 374, 426, 478, 530, 556, 582, and 634; and

a light chain variable region comprising an amino acid sequence selected from any of SEQ ID NOs;

23, 75, 127, 179, 231, 283, 335, 387, 439, 491, 543, 569, 595, and 647.

3. The antibody or antigen-binding fragment thereof of claim 1, wherein the antibody comprises:

a heavy chain comprising an amino acid sequence selected from any of SEQ ID NOs;

12, 64, 116, 168, 220, 272, 324, 376, 428, 480, 584, and 636; and

a light chain comprising an amino acid sequence selected from any of SEQ ID NOs;

25, 77, 129, 181, 233, 285, 337, 389, 441, 493, 597, and 649.

4. The antibody or antigen-binding fragment thereof of claim 1, wherein the antibody comprises:

a heavy chain comprising an amino acid sequence selected from any of SEQ ID NOs;

38, 90, 142, 194, 246, 298, 350, 402, 454, 506, 532, 558, 610, and 662; and

a light chain comprising an amino acid sequence selected from any of SEQ ID NOs;

51, 103, 155, 207, 259, 311, 363, 415, 467, 519, 545, 571, 623, and 675.

5. The antibody or antigen-binding fragment thereof of claim 1, wherein the antibody comprises:

(a) HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs;

1, 2, and 3, respectively, and LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs;

14, 15, and 16, respectively;

(b) HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs;

4, 5, and 6, respectively, and LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs;

17, 18, and 19, respectively;

(c) HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs;

7, 8, and 9, respectively, and LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs;

20, 21, and 22, respectively;

(d) HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs;

53, 54, and 55, respectively, and LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs;

66, 67, and 68 respectively;

(e) HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs;

56, 57, and 58, respectively, and LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs;

69, 70, and 71 respectively;

(f) HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs;

59, 60, and 61, respectively, and LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs;

72, 73, and 74 respectively;

(g) HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs;

105, 106, and 107 respectively, and LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs;

118, 119, 120, respectively;

(h) HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs;

108, 109, and 110 respectively, and LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs;

121, 122, 123, respectively;

(i) HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs;

111, 112, and 113 respectively, and LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs;

124, 125, 126, respectively;

(j) HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs;

157, 158, and 159, respectively, and LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs;

170, 171, 172, respectively;

(k) HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs;

160, 161, and 162, respectively, and LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs;

173, 174, 175, respectively;

(l) HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs;

163, 164, and 165, respectively, and LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs;

176, 177, 178, respectively;

(m) HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs;

209, 210, and 211, respectively, and LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs;

222, 223, and 224, respectively;

(n) HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs;

212, 213, and 214, respectively, and LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs;

225, 226, and 227, respectively;

(o) HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs;

215, 216, and 217 respectively, and LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs;

228, 229, and 230, respectively;

(p) HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs;

261, 262, and 263, respectively, and LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs;

274, 275, and 276, respectively;

(q) HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs;

264, 265, and 266, respectively, and LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs;

277, 278, and 279, respectively;

(r) HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs;

267, 268, and 269, respectively, and LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs;

280, 281, and 282, respectively;

(s) HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs;

313, 314, and 315, respectively, and LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs;

326, 327, and 328, respectively;

(t) HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs;

316, 317, and 318, respectively, and LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs;

329, 330, and 331, respectively;

(u) HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs;

319, 320, and 321, respectively, and LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs;

332, 333, and 334, respectively;

(v) HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs;

365, 366, and 367, respectively, and LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs;

378, 379, and 380, respectively;

(w) HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs;

368, 369, and 370, respectively, and LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs;

381, 382, and 383, respectively;

(x) HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs;

371, 372, and 373, respectively, and LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs;

384, 385, and 386, respectively;

(y) HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs;

417, 418, and 419, respectively, and LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs;

430, 431, and 432, respectively;

(z) HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs;

420, 421, and 422, respectively, and LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs;

433, 434, and 435, respectively;

(aa) HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs;

423, 424, and 425, respectively, and LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs;

436, 437, and 438, respectively;

(bb) HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs;

469, 470, and 471, respectively, and LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs;

482, 483, and 484, respectively;

(cc) HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs;

472, 473, and 474, respectively, and LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs;

485, 486, and 487, respectively;

(dd) HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs;

475, 476, and 477, respectively, and LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs;

488, 489, and 490, respectively;

(ee) HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs;

521, 522, and 523, respectively, and LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs;

534, 535, and 536, respectively;

(ff) HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs;

524, 525, and 526, respectively, and LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs;

537, 538, and 539, respectively;

(gg) HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs;

527, 528, and 529, respectively, and LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs;

540, 541, and 542, respectively;

(hh) HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs;

547, 548, and 549, respectively, and LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs;

560, 561, and 562, respectively;

(ii) HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs;

550, 551, and 552, respectively, and LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs;

563, 564, and 565, respectively;

(jj) HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs;

553, 554, and 555, respectively, and LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs;

566, 567, and 568, respectively;

(kk) HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs;

573, 574, and 575, respectively, and LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs;

586, 587, and 588, respectively;

(ll) HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs;

576, 577, and 578, respectively, and LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs;

589, 590, and 591, respectively;

(mm) HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs;

579, 580, and 581, respectively, and LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs;

592, 593, and 594, respectively;

(nn) HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs;

625, 626, and 627, respectively, and LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs;

638, 639, and 640, respectively;

(oo) HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs;

628, 629, and 630, respectively, and LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs;

641, 642, and 643, respectively;

or

(pp) HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs;

631, 632, and 633, respectively, and LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs;

644, 645, and 646, respectively.

6. The isolated antibody or antigen-binding fragment thereof of claim 1, comprising:

(a) A VH sequence of SEQ ID NO;

10 and a VL sequence of SEQ ID NO;

23;

(b) A VH sequence of SEQ ID NO;

62 and a VL sequence of SEQ ID NO;

75;

(c) A VH sequence of SEQ ID NO;

114 and VL sequence of SEQ ID NO;

127;

(d) A VH sequence of SEQ ID NO;

166 and a VL sequence of SEQ ID NO;

179;

(e) A VH sequence of SEQ ID NO;

218 and a VL sequence of SEQ ID NO;

231;

(f) A VH sequence of SEQ ID NO;

270 and a VL sequence of SEQ ID NO;

283;

(g) A VH sequence of SEQ ID NO;

322 and a VL sequence of SEQ ID NO;

335;

(h) A VH sequence of SEQ ID NO;

374 and VL sequence of SEQ ID NO;

387;

(i) A VH sequence of SEQ ID NO;

426 and a VL sequence of SEQ ID NO;

439;

(j) A VH sequence of SEQ ID NO;

478 and a VL sequence of SEQ ID NO;

491;

(k) A VH sequence of SEQ ID NO;

530 and a VL sequence of SEQ ID NO;

543;

(l) A VH sequence of SEQ ID NO;

556 and a VL sequence of SEQ ID NO;

569;

(m) A VH sequence of SEQ ID NO;

582 and a VL sequence of SEQ ID NO;

595;

or

(n) A VH sequence of SEQ ID NO;

634 and a VL sequence of SEQ ID NO;

647.

7. The isolated antibody or antigen-binding fragment thereof of claim 1, comprising:

(a) A heavy chain sequence of SEQ ID NO;

12; and

a light chain sequence of SEQ ID NO;

25;

(b) A heavy chain sequence of SEQ ID NO;

64; and

a light chain sequence of SEQ ID NO;

77;

(c) A heavy chain sequence of SEQ ID NO;

116; and

a light chain sequence of SEQ ID NO;

129;

(d) A heavy chain sequence of SEQ ID NO;

168; and

a light chain sequence of SEQ ID NO;

181;

(e) A heavy chain sequence of SEQ ID NO;

220; and

a light chain sequence of SEQ ID NO;

233;

(f) A heavy chain sequence of SEQ ID NO;

272; and

a light chain sequence of SEQ ID NO;

285;

(g) A heavy chain sequence of SEQ ID NO;

324; and

a light chain sequence of SEQ ID NO;

337;

(h) A heavy chain sequence of SEQ ID NO;

376; and

a light chain sequence of SEQ ID NO;

389;

(i) A heavy chain sequence of SEQ ID NO;

428; and

a light chain sequence of SEQ ID NO;

441;

(j) A heavy chain sequence of SEQ ID NO;

480; and

a light chain sequence of SEQ ID NO;

493;

(k) A heavy chain sequence of SEQ ID NO;

584; and

a light chain sequence of SEQ ID NO;

597;

or

(l) A heavy chain sequence of SEQ ID NO;

636; and

a light chain sequence of SEQ ID NO;

649.

8. The isolated antibody or antigen-binding fragment thereof of claim 1, comprising:

(a) A heavy chain sequence of SEQ ID NO;

38; and

a light chain sequence of SEQ ID NO;

51;

(b) A heavy chain sequence of SEQ ID NO;

90; and

a light chain sequence of SEQ ID NO;

103;

(c) A heavy chain sequence of SEQ ID NO;

142; and

a light chain sequence of SEQ ID NO;

155;

(d) A heavy chain sequence of SEQ ID NO;

194; and

a light chain sequence of SEQ ID NO;

207;

(e) A heavy chain sequence of SEQ ID NO;

246; and

a light chain sequence of SEQ ID NO;

259;

(f) A heavy chain sequence of SEQ ID NO;

298; and

a light chain sequence of SEQ ID NO;

311;

(g) A heavy chain sequence of SEQ ID NO;

350; and

a light chain sequence of SEQ ID NO;

363;

(h) A heavy chain sequence of SEQ ID NO;

402; and

a light chain sequence of SEQ ID NO;

415;

(i) A heavy chain sequence of SEQ ID NO;

454; and

a light chain sequence of SEQ ID NO;

467;

(j) A heavy chain sequence of SEQ ID NO;

506; and

a light chain sequence of SEQ ID NO;

519;

(k) A heavy chain sequence of SEQ ID NO;

532; and

a light chain sequence of SEQ ID NO;

545;

(l) A heavy chain sequence of SEQ ID NO;

558; and

a light chain sequence of SEQ ID NO;

571;

(m) A heavy chain sequence of SEQ ID NO;

610; and

a light chain sequence of SEQ ID NO;

623;

or

(n) A heavy chain sequence of SEQ ID NO;

662; and

a light chain sequence of SEQ ID NO;

675.

9. The isolated antibody or antigen binding fragment thereof of claim 1, comprising:

(a) a HCDR1 comprising the amino acid sequence selected from SEQ ID NOs;

157, 160, or 163;

(b) a HCDR2 comprising the amino acid sequence selected from SEQ ID NOs;

158, 161, or 164;

(c) a HCDR3 comprising the amino acid sequence selected from SEQ ID NOs;

159, 315, 367, 419, 471, 523, 549, 575, or 627;

(d) a LCDR1 comprising the amino acid sequence selected from SEQ ID NOs;

170, 173, or 176;

(e) a LCDR2 comprising the amino acid sequence selected from SEQ ID NOs;

171, 174, or 177; and

(f) a LCDR3 comprising the amino acid sequence of SEQ ID NO;

172.

10. The isolated antibody or antigen binding fragment thereof of claim 1, comprising:

(a) a HCDR1 comprising the amino acid sequence selected from SEQ ID NOs;

157, 160, or 163;

(b) a HCDR2 comprising the amino acid sequence selected from SEQ ID NOs;

158, 161, or 164;

(c) a HCDR3 comprising the amino acid sequence EQX₁PX₂X₃GX₄GGX₅PX₆EAMDV (SEQ ID NO;

     683), wherein X₁ is D or S, X₂ is E or S, X₃ is Y, F, A, or S;

X₄ is Y or F;

X₅ is F or Y, and X₆ is Y or F;

(d) a LCDR1 comprising the amino acid sequence selected from SEQ ID NOs;

170, 173, or 176;

(e) a LCDR2 comprising the amino acid sequence selected from SEQ ID NOs;

171, 174, or 177; and

(f) a LCDR3 comprising the amino acid sequence of SEQ ID NO;

172.

11. The isolated antibody or antigen-binding fragment thereof of claim 10, comprising:

(a) a HCDR1 comprising the amino acid sequence selected from SEQ ID NO;

157, 160, or 163;

(b) a HCDR2 comprising the amino acid sequence selected from SEQ ID NO;

158, 161, or 164;

(c) a HCDR3 comprising the amino acid sequence of SEQ ID NO;

159, 315, 367, or 419;

(d) a LCDR1 comprising the amino acid sequence selected from SEQ ID NOs;

170, 173, or 176;

(e) a LCDR2 comprising the amino acid sequence selected from SEQ ID NOs;

171, 174, or 177; and

(f) a LCDR3 comprising the amino acid sequence of SEQ ID NO;

172.

12. The isolated antibody or antigen-binding fragment thereof of claim 10, comprising:

(a) a HCDR1 comprising the amino acid sequence selected from SEQ ID NO;

417;

(b) a HCDR2 comprising the amino acid sequence selected from SEQ ID NO;

418;

(c) a HCDR3 comprising the amino acid sequence of SEQ ID NO;

419;

(d) a LCDR1 comprising the amino acid sequence selected from SEQ ID NOs;

430;

(e) a LCDR2 comprising the amino acid sequence selected from SEQ ID NOs;

431; and

(f) a LCDR3 comprising the amino acid sequence of SEQ ID NO;

432.

13. The antibody or antigen-binding fragment thereof of claim 1 comprising:

(a) a HCDR1 comprising the amino acid sequence selected from SEQ ID NO;

417;

(b) a HCDR2 comprising the amino acid sequence selected from SEQ ID NO;

418;

(c) a HCDR3 comprising the amino acid sequence of SEQ ID NO;

419;

(d) a LCDR1 comprising the amino acid sequence selected from SEQ ID NOs;

430;

(e) a LCDR2 comprising the amino acid sequence selected from SEQ ID NOs;

431; and

(f) a LCDR3 comprising the amino acid sequence of SEQ ID NO;

432;

wherein the antibody or antigen-binding fragment thereof is afucosylated.

14. The afucosylated antibody or antigen-binding fragment thereof of claim 13, comprising a variable heavy chain region comprising the amino acid sequence of SEQ ID NO:

426 and a light chain variable region comprising the amino acid sequence of SEQ ID NO;

441.

15. The afucosylated antibody or antigen-binding fragment thereof of claim 13, comprising a heavy chain comprising the amino acid sequence of SEQ ID NO:

428 and a light chain comprising the amino acid sequence of SEQ ID NO;

441.

18. The isolated antibody or antigen-binding fragment thereof of claim 1, wherein the antibody is afucosylated.

19. The isolated antibody or antigen-binding fragment thereof of claim 1, wherein the Fc portion of the antibody is modified to enhance ADCC activity.

20. The isolated antibody or antigen-binding fragment thereof of claim 1, wherein the antibody or antigen-binding fragment thereof selectively binds human CD32b over human CD32a.

21. The isolated antibody or antigen-binding fragment thereof of claim 1, wherein the antibody or antigen-binding fragment thereof is an IgG selected from the group consisting of an IgG1, an IgG2, an IgG3 and an IgG4.

22. The isolated antibody or antigen-binding fragment thereof of claim 1, wherein the isolated antibody or antigen-binding fragment is selected from the group consisting of:

a monoclonal antibody, a chimeric antibody, a single chain antibody, a Fab and a scFv.

23. The isolated antibody or antigen-binding fragment thereof of claim 1, wherein the antibody or antigen-binding fragment thereof is chimeric, humanized or fully human.

24. The isolated antibody or antigen-binding fragment thereof of claim 1, wherein the isolated antibody or antigen-binding fragment inhibits binding of human CD32b to immunoglobulin Fc domains.

25. The isolated antibody or antigen-binding fragment thereof of claim 1, wherein the isolated antibody or antigen-binding fragment thereof is a component of an immunoconjugate.

26. A multivalent antibody, wherein one arm of the antibody comprises the isolated antibody or antigen-binding fragments of claim 1.

27. The multivalent antibody of claim 26, wherein the antibody is a bispecific antibody.

28. A composition comprising the isolated antibody or antigen-binding fragment thereof of claim 1, in combination with one or more additional antibodies that bind a cell surface antigen that is co-expressed with CD32b on a cell.

29. The composition of claim 28, wherein the cell surface antigen and CD32b are co-expressed on B cells.

30. The composition of claim 28, wherein the cell surface antigen is selected from the group consisting of CD20, CD38, CD52, CS1/SLAMF7, CD56, CD138, KiR, CD19, CD40, Thy-1, Ly-6, CD49, Fas, Cd95, APO-1, EGFR, HER2, CXCR4, HLA molecules, GM1, CD22, CD23, CD80, CD74, or DRD.

31. The composition of claim 28, wherein the cell surface antigen is selected from the group consisting of CD20, CD38, CS1/SLAMF7 and CD52.

32. The composition of claim 28, wherein the additional antibody is selected from the group consisting of rituximab, elotuzumab, ofatumumab, obinutumumab, daratumumab, and alemtuzumab.

33. The composition of claim 28 further comprising an additional therapeutic compound.

34. A composition comprising the isolated antibody or antigen-binding fragment thereof of claim 1 in combination with an additional therapeutic compound.

35. The composition of claim 34, wherein the additional therapeutic compound is an immunomodulator.

36. The composition of claim 35, wherein the immunomodulator is IL15 or the immunomodulator is an agonist of a costimulatory molecule selected from OX40, CD2, CD27, CDS, ICAM-1, LFA-1 (CD11a/CD18), ICOS (CD278), 4-1BB (CD137), GITR, CD30, CD40, BAFFR, HVEM, CD7, LIGHT, NKG2C, SLAMF7, NKp80, CD160, B7-H3, CD83 ligand, and STING.

37. The composition of claim 35, wherein the immunomodulator is an inhibitor molecule of a target selected from PD-1, PD-L1, PD-L2, CTLA-4, TIM-3, LAG-3, CEACAM-1, CEACAM-3, CEACAM-5, VISTA, BTLA, TIGIT, LAIR1, CD160, 2B4, TGFR beta, and IDO.

38. The composition of claim 34, wherein the additional therapeutic compound is selected from ofatumumab, ibrutinib, belinostat, romidepsin, brentuximab vedotin, obinutuzumab, pralatrexate, pentostatin, dexamethasone, idelalisib, ixazomib, liposomal doxyrubicin, pomalidomide, panobinostat, elotuzumab, daratumumab, alemtuzumab, thalidomide, and lenalidomide.

39. The composition of claim 33, wherein the additional therapeutic compound is selected from ibrutinib, belinostat, romidepsin, brentuximab vedotin, pralatrexate, pentostatin, dexamethasone, idelalisib, ixazomib, liposomal doxyrubicin, pomalidomide, panobinostat, thalidomide, and lenalidomide

40. A pharmaceutical composition comprising the isolated antibody or antigen-binding fragment thereof of claim 1, or a multivalent antibody comprising the antibody or antigen-binding fragment thereof of claim 1, and a pharmaceutically acceptable carrier.

42. A method of treating a CD32b-related condition in a subject in need thereof comprising administering to the subject a therapeutically effective amount of the antibody or antigen-binding fragment thereof of claim 1, or a multivalent antibody comprising the antibody or antigen-binding fragment thereof of claim 1.

46. The method of claim 42 wherein the CD32b-related condition is selected from B cell malignancies, Hodgkins lymphoma, Non-Hodgkins lymphoma, multiple myeloma, diffuse large B cell lymphoma, acute lymphocytic leukemia, chronic lymphocytic leukemia, small lymphocytic lymphoma, diffuse small cleaved cell lymphoma, MALT lymphoma, mantel cell lymphoma, marginal zone lymphoma, follicular lymphoma, or systemic light chain amyloidosis.

47. A nucleic acid encoding the antibody or antigen-binding fragment thereof of claim 1.

48. A vector comprising the nucleic acid of claim 47.

49. A host cell comprising the nucleic acid of claim 47, or comprising a vector comprising the nucleic acid of claim 47.

50. A method of producing the antibody or antigen-binding fragment thereof of claim 1, the method comprising:

culturing a host cell expressing a nucleic acid encoding the antibody; and

collecting the antibody from the culture.

52. A method of treating a patient who is resistant or refractory to treatment using an antibody that binds to a cell surface antigen that is co-expressed with CD32b on a cell, comprising co-administering the antibody with any one of the isolated anti-CD32b antibodies or an antigen-binding fragment thereof of claim 1, or a multivalent antibody comprising the antibody or antigen-binding fragment thereof of claim 1.

61. The isolated antibody or antigen binding fragment of claim 55 comprising the antibody of claim 1.

16. An isolated antibody or antigen-binding fragment thereof, wherein the antibody or antigen-binding fragment thereof comprises a heavy chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence selected from the group consisting of SEQ ID NOs:

10, 62, 114, 166, 218, 270, 322, 374, 426, 478, 530, 556, 582, and 634; and

a light chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence selected from the group consisting of SEQ ID NOs;

23, 75, 127, 179, 231, 283, 335, 387, 439, 491, 543, 569, 595, and 647;

wherein the antibody specifically binds to human CD32b protein.

17. The isolated antibody or antigen-binding fragment thereof of claim 16, wherein the antibody or antigen-binding fragment thereof comprises a heavy chain comprising an amino acid sequence that is at least 90% identical to the amino acid sequence selected from the group consisting of SEQ ID NOs:

12, 38, 64, 90, 116, 142, 168, 194, 220, 246, 272, 298, 324, 350, 376, 402, 428, 454, 480, 506, 532, 558, 584, 610, 636, and 662; and

a light chain comprising an amino acid sequence that is at least 90% identical to the amino acid sequence selected from the group consisting of SEQ ID NOs;

25, 51, 77, 103, 129, 155, 181, 207, 233, 259, 285, 311, 337, 363, 389, 415, 441, 467, 493, 519, 545, 571, 597, 623, 649, and 675;

wherein the antibody specifically binds to human CD32b protein.

41. (canceled)

43. (canceled)

44. (canceled)

45. (canceled)

51. (canceled)

53. (canceled)

54. (canceled)

55. An isolated antibody or antigen binding fragment thereof that specifically binds to CD32b within the Fc binding domain of CD32b.

56. The isolated antibody or antigen binding fragment of claim 55, wherein the antibody binds within amino acid residues 107-123 (VLRCHSWKDKPLVKVTF (SEQ ID NO:

685)) of CD32b.

57. The isolated antibody or antigen binding fragment of claim 55, wherein the antibody prevents or reduces CD32b binding to the immunoglobulin Fc domain of a second antibody that binds to a tumor antigen co-expressed with CD32b on a B-cell.

58. The isolated antibody or antigen binding fragment of claim 57, wherein the second antibody binds to a tumor antigen selected from the group consisting of CD20, CD38, CD52, CS1/SLAMF7, CD56, CD138, KiR, CD19, CD40, Thy-1, Ly-6, CD49, Fas, Cd95, APO-1, EGFR, HER2, CXCR4, HLA molecules, GM1, CD22, CD23, CD80, CD74, or DRD.

59. The isolated antibody or antigen binding fragment of claim 57, wherein the second antibody binds to a tumor antigen selected from the group consisting of CD20, CD38, CS1/SLAMF7 and CD52.

60. The isolated antibody or antigen binding fragment of claim 57, wherein the second antibody is selected from the group consisting of rituximab, elotuzumab, ofatumumab, obinutumumab, daratumumab, and alemtuzumab.

62. An isolated antibody or antigen binding fragment thereof that specifically binds to CD32b and inhibits or reduces CD32b immunoreceptor tyrosine-based inhibition motif (ITIM) signaling mediated by a second antibody that binds to a tumor antigen co-expressed with CD32b on a B-cell.

63. A method of inhibiting or reducing CD32b ITIM signaling that is induced by administration of a therapeutic antibody that binds to a tumor antigen co-expressed with CD32b on a B-cell comprising administering an isolated antibody or antigen binding fragment thereof that specifically binds to the Fc binding domain of CD32b.

64. The method of claim 63, wherein the isolated antibody or antigen binding fragment thereof does not stimulate ITIM signaling.

65. The method of claim 63, wherein the therapeutic antibody binds to a tumor antigen selected from the group consisting of CD20, CD38, CD52, CS1/SLAMF7, CD56, CD138, KiR, CD19, CD40, Thy-1, Ly-6, CD49, Fas, Cd95, APO-1, EGFR, HER2, CXCR4, HLA molecules, GM1, CD22, CD23, CD80, CD74, or DRD.

66. The method of claim 63, wherein the therapeutic antibody binds to a tumor antigen selected from the group consisting of CD20, CD38, CS1/SLAMF7 and CD52.

67. The method of claim 63, wherein the therapeutic antibody is selected from the group consisting of rituximab, elotuzumab, ofatumumab, obinutumumab, daratumumab, and alemtuzumab.

68. (canceled)