IL-17 binding proteins

• US 8,835,610 B2
• Filed: 03/05/2010
• Issued: 09/16/2014
• Est. Priority Date: 03/05/2009
• Status: Active Grant

• Current Assignee: Abbvie Incorporated
• Original Assignee: Abbvie Incorporated
• Inventors: Hsieh, Chung-Ming, Kutskova, Yuliya, Memmott, John E., Perez, Jennifer M., Zhong, Suju, Tarcsa, Edit, Clabbers, Anca, Hugunin, Margaret
• Primary Examiner(s): Yu, Misook
• Assistant Examiner(s): Moseley, II, Nelson B
• Application Number:
  US12/718,841
• Publication Number:
  US 20100266531A1
• Time in Patent Office: 1,656 Days
• Field of Search: None
• US Class Current: 530/388.23
• 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 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 39/3955 against proteinaceous materials, e.g. enzymes, hormones, lymphokines
• CPC Class Codes: A61P 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• CPC Class Codes: A61P 1/16 for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 11/02 Nasal agents, e.g. decongestants
• CPC Class Codes: A61P 11/06 Antiasthmatics
• CPC Class Codes: A61P 13/00 Drugs for disorders of the urinary system
• CPC Class Codes: A61P 13/12 of the kidneys
• CPC Class Codes: A61P 15/00 Drugs for genital or sexual disorders for disorders of sex hormones A61P5/24; Contraceptives
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 17/02 for treating wounds, ulcers, burns, scars, keloids, or the like
• CPC Class Codes: A61P 17/04 Antipruritics
• CPC Class Codes: A61P 17/06 Antipsoriatics
• CPC Class Codes: A61P 17/14 for baldness or alopecia
• CPC Class Codes: A61P 19/00 Drugs for skeletal disorders
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 19/04 for non-specific disorders of the connective tissue
• CPC Class Codes: A61P 21/02 : Muscle relaxants, e.g. for tetanus or cramps
• CPC Class Codes: A61P 21/04 : for myasthenia gravis
• CPC Class Codes: A61P 25/00 : Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/06 : Antimigraine agents
• CPC Class Codes: A61P 25/14 : for treating abnormal movements, e.g. chorea, dyskinesia
• CPC Class Codes: A61P 25/16 : Anti-Parkinson drugs
• CPC Class Codes: A61P 25/28 : for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: A61P 27/02 : Ophthalmic agents
• CPC Class Codes: A61P 29/00 : Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 3/10 : for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 31/00 : Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 31/04 : Antibacterial agents
• CPC Class Codes: A61P 31/10 : Antimycotics
• CPC Class Codes: A61P 31/12 : Antivirals
• CPC Class Codes: A61P 31/14 : for RNA viruses
• CPC Class Codes: A61P 31/16 : for influenza or rhinoviruses
• CPC Class Codes: A61P 33/06 : Antimalarials
• CPC Class Codes: A61P 35/00 : Antineoplastic agents
• CPC Class Codes: A61P 35/02 : specific for leukemia
• CPC Class Codes: A61P 37/00 : Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 37/06 : Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 37/08 : Antiallergic agents antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14
• CPC Class Codes: A61P 5/14 : of the thyroid hormones, e.g. T3, T4
• CPC Class Codes: A61P 5/18 : of the parathyroid hormones
• CPC Class Codes: A61P 7/00 : Drugs for disorders of the blood or the extracellular fluid
• CPC Class Codes: A61P 7/06 : Antianaemics
• CPC Class Codes: A61P 9/00 : Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/06 : Antiarrhythmics
• CPC Class Codes: A61P 9/10 : for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: C07K 16/241 : Tumor Necrosis Factors
• CPC Class Codes: C07K 16/244 : Interleukins [IL]
• CPC Class Codes: C07K 16/468 : Immunoglobulins having two or more different antigen binding sites, e.g. multifunctional antibodies
• CPC Class Codes: C07K 2317/21 : from primates, e.g. man
• CPC Class Codes: C07K 2317/31 : multispecific
• CPC Class Codes: C07K 2317/50 : characterized by immunoglobulin fragments
• CPC Class Codes: C07K 2317/565 : Complementarity determining region [CDR]
• CPC Class Codes: C07K 2317/64 : comprising a combination of variable region and constant region components
• 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
• CPC Class Codes: Y02A 50/30 : Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

Proteins that bind IL-17 and/or IL-17F are described along with their use in compositions and methods for treating, preventing, and diagnosing IL-17 related diseases and for detecting IL-17 in cells, tissues, samples, and compositions.

Claims

1. An antibody or antigen binding portion thereof comprising an antigen binding domain, wherein the antibody or antigen binding portion thereof binds human IL-17, and the antigen binding domain comprises six CDRs:

CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR-L3, wherein;

CDR-H1 has an amino acid sequence S-Y-G-I-S (residues 31-35 of SEQ ID NO;

46) or a modification of said amino acid sequence by a substitution of at least one amino acid residue, wherein;

the substitution of S at position 1 is selected from the group consisting of G, T, V, and R;

the substitution of G at position 3 is selected from the group consisting of D, V, S, A, C, and I;

the substitution of I at position 4 is selected from the group consisting of F, T, Y, M, and V; and

the substitution of S at position 5 is selected from the group consisting of G, C, N, V, and H;

CDR-H2 has an amino acid sequence G-I-T-P-I-L-G-T-A-N-Y-A-Q-K-F-Q-G (residues 50-66 of SEQ ID NO;

46) or a modification of said amino acid sequence by a substitution of at least one amino acid residue, wherein;

the substitution of I at position 2 is V;

the substitution of P at position 4 is selected from the group consisting of H, N, T, L, I, V, S, and F;

the substitution of I at position 5 is selected from the group consisting of F, I, M, V, S, and L;

the substitution of L at position 6 is F;

the substitution of G at position 7 is selected from the group consisting of M, L, E, and A;

the substitution of T at position 8 is selected from the group consisting of I, S, W, A, F, L, M, V, and H;

the substitution of A at position 9 is selected from the group consisting of T, V, S, E, D, P, I, G, and R;

the substitution of N at position 10 is selected from the group consisting of D, Y, S, T, V, and I; and

the substitution of G at position 17 is D;

CDR-H3 has an amino acid sequence E-P-N-D-F-W-N-G-Y-Y-T-T-H-H-F-D-Y (residues 99-115 of SEQ ID NO;

46) or a modification of said amino acid sequence by substitution of at least one amino acid residue, wherein;

the substitution of E at position 1 is selected from the group consisting of D and V;

the substitution of P at position 2 is selected from the group consisting of S and T;

the substitution of N at position 3 is selected from the group consisting of S, T, and H;

the substitution of D at position 4 is selected from the group consisting of E and A;

the substitution of Y at position 10 is F;

the substitution of T at position 11 is selected from the group consisting of A, S, D, P, N, C, and V;

the substitution of H at position 13 is selected from the group consisting of D, Q, N, and L;

the substitution of H at position 14 is selected from the group consisting of D, Y, and N;

the substitution of F at position 15 is selected from the group consisting of L and Y; and

the substitution of Y at position 17 is selected from the group consisting of S, L, N, F, C, I, H, A, and D;

CDR-L1 has an amino acid sequence R-A-S-Q-N-I-G-S-A-L-H (residues 24-34 of SEQ ID NO;

47) or a modification of said amino acid sequence by substitution of at least one amino acid residue, wherein;

the substitution of R at position 1 is W;

the substitution of A at position 2 is V;

the substitution of N at position 5 is selected from the group consisting of D, E, A, and I;

the substitution of G at position 7 is selected from the group consisting of D and E;

the substitution of S at position 8 is selected from the group consisting of Y, A, E, F, T, and G; and

the substitution of A at position 9 is selected from the group consisting of E, D, S, and G;

CDR-L2 has an amino acid sequence;

Y-A-S-Q-S-I-S (residues 50-56 of SEQ ID NO;

47) or a modification of said amino acid sequence by substitution of at least one amino acid residue, wherein;

the substitution of Q at position 4 is selected from the group consisting of H, Y, E, N, S, and W;

the substitution of S at position 5 is selected from the group consisting of P and C;

the substitution of I at position 6 is selected from the group consisting of V, T, N, A, M, L, G, S, F, P, and Q; and

the substitution of S at position 7 is P; and

CDR-L3 has an amino acid sequence;

H-Q-S-T-S-L-P-H-T (residues 89-97 of SEQ ID NO;

47) or a modification of said amino acid sequence by substitution of at least one amino acid residue, wherein;

the substitution of S at position 3 is selected from the group consisting of T and G;

the substitution of T at position 4 is selected from the group consisting of D, A, Y, S, F, N, I, E, and M;

the substitution of S at position 5 is selected from the group consisting of D, N, G, I, T, F, Y, W, C, E, R, V, L, and M;

the substitution of H at position 8 is selected from the group consisting of Y, Q, F, I, V, D, and N; and

the substitution of T at position 9 is selected from the group consisting of S, A, I, N, and L; and

wherein said substitution of at least one amino acid residue does not inhibit the ability of said antibody or antigen binding portion thereof to bind human IL-17.

2. The antibody or antigen binding portion thereof according to claim 1, wherein the CDRs are selected from the group consisting of:

SYGIS, residues 31-35 of SEQ ID NO;

359 (CDR-H1),

SYGIC, residues 31-35 of SEQ ID NO;

362 (CDR-H1),

SYGIV, residues 31-35 of SEQ ID NO;

363 (CDR-H1),

GYGIS, residues 31-35 of SEQ ID NO;

368 (CDR-H1),

TYGIS, residues 31-35 of SEQ ID NO;

372 (CDR-H1),

GYGTS, residues 31-35 of SEQ ID NO;

383 (CDR-H1),

GYGIG, residues 31-35 of SEQ ID NO;

389 (CDR-H1),

SYGIG, residues 31-35 of SEQ ID NO;

394 (CDR-H1),

SYGFS, residues 31-35 of SEQ ID NO;

405 (CDR-H1),

SYGYN, residues 31-35 of SEQ ID NO;

406 (CDR-H1),

TYGMN, residues 31-35 of SEQ ID NO;

408 (CDR-H1),

SYGFG, residues 31-35 of SEQ ID NO;

409 (CDR-H1),

SYGTS, residues 31-35 of SEQ ID NO;

430 (CDR-H1),

SYCTS, residues 31-35 of SEQ ID NO;

431 (CDR-H1),

SYSTS, residues 31-35 of SEQ ID NO;

432 (CDR-H1),

SYVIS, residues 31-35 of SEQ ID NO;

439 (CDR-H1),

VYGFS, residues 31-35 of SEQ ID NO;

440 (CDR-H1),

TYGFS, residues 31-35 of SEQ ID NO;

441 (CDR-H1),

SYVFS, residues 31-35 of SEQ ID NO;

442 (CDR-H1),

SYGVS, residues 31-35 of SEQ ID NO;

443 (CDR-H1),

SYDFS, residues 31-35 of SEQ ID NO;

445 (CDR-H1),

GYDFS, residues 31-35 of SEQ ID NO;

447 (CDR-H1),

SYIIS, residues 31-35 of SEQ ID NO;

452 (CDR-H1),

SYGYS, residues 31-35 of SEQ ID NO;

453 (CDR-H1),

SYDYS, residues 31-35 of SEQ ID NO;

457 (CDR-H1),

GYVYS, residues 31-35 of SEQ ID NO;

460 (CDR-H1),

RYDFS, residues 31-35 of SEQ ID NO;

464 (CDR-H1),

SYVVS, residues 31-35 of SEQ ID NO;

468 (CDR-H1),

SYGFH, residues 31-35 of SEQ ID NO;

469 (CDR-H1),

GITTFFGITDYAQKFQG, residues 50-66 of SEQ ID NO;

359 (CDR-H2),

GITNFFGWTDYAQKFQG, residues 50-66 of SEQ ID NO;

360 (CDR-H2),

GITNFFGAVDYAQKFQG, residues 50-66 of SEQ ID NO;

361 (CDR-H2),

GITNFFGTTDYAQKFQG, residues 50-66 of SEQ ID NO;

362 (CDR-H2),

GITTFFGATDYAQKFQG, residues 50-66 of SEQ ID NO;

363 (CDR-H2),

GITIFFGTVDYAQKFQG, residues 50-66 of SEQ ID NO;

366 (CDR-H2),

GITHFFGTVDYAQKFQG, residues 50-66 of SEQ ID NO;

367 (CDR-H2),

GITPFFGWADYAQKFQG, residues 50-66 of SEQ ID NO;

368 (CDR-H2),

GITPFFGWTDYAQKFQG, residues 50-66 of SEQ ID NO;

370 (CDR-H2),

GITHFFGSTDYAQKFQG, residues 50-66 of SEQ ID NO;

374 (CDR-H2),

GITLFFGTVDYAQKFQG, residues 50-66 of SEQ ID NO;

378 (CDR-H2),

GITLFFGISDYAQKFQG, residues 50-66 of SEQ ID NO;

380 (CDR-H2),

GITNFFGMEDYAQKFQG, residues 50-66 of SEQ ID NO;

382 (CDR-H2),

GITHFFGAVDYAQKFQG, residues 50-66 of SEQ ID NO;

383 (CDR-H2),

GITNFFGIVDYAQKFQG, residues 50-66 of SEQ ID NO;

387 (CDR-H2),

GITPFFGFADYAQKFQG, residues 50-66 of SEQ ID NO;

389 (CDR-H2),

GVTTFFGFADYAQKFQG, residues 50-66 of SEQ ID NO;

390 (CDR-H2),

GITTFFGVADYAQKFQGR, residues 50-66 of SEQ ID NO;

391 (CDR-H2),

GITHFFGMTDYAQKFQG, residues 50-66 of SEQ ID NO;

392 (CDR-H2),

GITTFFGTTDYAQKFQG, residues 50-66 of SEQ ID NO;

393 (CDR-H2),

GITNFFGVEDYAQKFQG, residues 50-66 of SEQ ID NO;

394 (CDR-H2),

GITHFFGISDYAQKFQG, residues 50-66 of SEQ ID NO;

395 (CDR-H2),

GITNFFGIRDYAQKFQG, residues 50-66 of SEQ ID NO;

396 (CDR-H2),

GITVFFGTADYAQKFQG, residues 50-66 of SEQ ID NO;

397 (CDR-H2),

GITLFFGTTDYAQKFQG, residues 50-66 of SEQ ID NO;

398 (CDR-H2),

GITHFFGMVDYAQKFQG, residues 50-66 of SEQ ID NO;

399 (CDR-H2),

GITNFFGSTDYAQKFQG, residues 50-66 of SEQ ID NO;

401 (CDR-H2),

GITHFFGITDYAQKFQG, residues 50-66 of SEQ ID NO;

403 (CDR-H2),

GITVFFGHVYYAQKFQG, residues 50-66 of SEQ ID NO;

405 (CDR-H2),

GITPFFGTADYAQKFQG, residues 50-66 of SEQ ID NO;

406 (CDR-H2),

GITPFFGLADYAQKFQG, residues 50-66 of SEQ ID NO;

407 (CDR-H2),

GITPFFGIADYAQKFQG, residues 50-66 of SEQ ID NO;

409 (CDR-H2),

GITPILGTANYAQKFQG, residues 50-66 of SEQ ID NO;

410 (CDR-H2),

GITPILGTANYAQKFQD, residues 50-66 of SEQ ID NO;

421 (CDR-H2),

GITFFFGAADYAQKFQG, residues 50-66 of SEQ ID NO;

429 (CDR-H2),

GITHFFGTTDYAQKFQG, residues 50-66 of SEQ ID NO;

430 (CDR-H2),

GITHFFGSADYAQKFQG, residues 50-66 of SEQ ID NO;

431 (CDR-H2),

GITHFFGTADYAQKFQG, residues 50-66 of SEQ ID NO;

432 (CDR-H2),

GITHFFLTTDYAQKFQG, residues 50-66 of SEQ ID NO;

435 (CDR-H2),

GITHMFATTDYAQKFQG, residues 50-66 of SEQ ID NO;

436 (CDR-H2),

GITPFLGATDYAQKFQG, residues 50-66 of SEQ ID NO;

437 (CDR-H2),

GITPFFGFIDYAQKFQG, residues 50-66 of SEQ ID NO;

438 (CDR-H2),

GITPFFGTVDYAQKFQG, residues 50-66 of SEQ ID NO;

439 (CDR-H2),

GITPFLGTVDYAQKFQG, residues 50-66 of SEQ ID NO;

440 (CDR-H2),

GITTFLGTVNYAQKFQG, residues 50-66 of SEQ ID NO;

441 (CDR-H2),

GITPLLGISDYAQKFQG, residues 50-66 of SEQ ID NO;

442 (CDR-H2),

GITTILGTSDYAQKFQG, residues 50-66 of SEQ ID NO;

443 (CDR-H2),

GITPIFGTGDYAQKFQG, residues 50-66 of SEQ ID NO;

444 (CDR-H2),

GITTFFESADYAQKFQG, residues 50-66 of SEQ ID NO;

445 (CDR-H2),

GITTFFGLADYAQKFQG, residues 50-66 of SEQ ID NO;

446 (CDR-H2),

GITPFFGSAYYAQKFQG, residues 50-66 of SEQ ID NO;

447 (CDR-H2),

GITPFFGSTDYAQKFQG, residues 50-66 of SEQ ID NO;

450 (CDR-H2),

GITPFFGIVNYAQKFQG, residues 50-66 of SEQ ID NO;

457 (CDR-H2),

GITTFFGASTYAQKFQG, residues 50-66 of SEQ ID NO;

458 (CDR-H2),

GITSFFGTEDYAQKFQG, residues 50-66 of SEQ ID NO;

459 (CDR-H2),

GITPFLGTAIYAQKFQG, residues 50-66 of SEQ ID NO;

461 (CDR-H2),

GITPILGTENYAQKFQG, residues 50-66 of SEQ ID NO;

462 (CDR-H2),

GITPFLGMSSYAQKFQG, residues 50-66 of SEQ ID NO;

463 (CDR-H2),

GITPFLGTSNYAQKFQG, residues 50-66 of SEQ ID NO;

464 (CDR-H2),

GITPFLGFSNYAQKFQG, residues 50-66 of SEQ ID NO;

465 (CDR-H2),

GITPFLGTADYAQKFQG, residues 50-66 of SEQ ID NO;

466 (CDR-H2),

GITTFLGTVVYAQKFQG, residues 50-66 of SEQ ID NO;

467 (CDR-H2),

GITPFFGTDNYAQKFQG, residues 50-66 of SEQ ID NO;

469 (CDR-H2),

GITPFFGLGTYAQKFQG, residues 50-66 of SEQ ID NO;

470 (CDR-H2),

GITPFFGAANYAQKFQG, residues 50-66 of SEQ ID NO;

471 (CDR-H2),

DPNEFWNGYYATHDFDY, residues 99-115 of SEQ ID NO;

359 (CDR-H3),

DPNEFWNGYYATHDFDI, residues 99-115 of SEQ ID NO;

364 (CDR-H3),

DPNEFWNGYYDTHDFDS, residues 99-115 of SEQ ID NO;

365 (CDR-H3),

DPNEFWNGYYNTHDFDY, residues 99-115 of SEQ ID NO;

366 (CDR-H3),

DPNEFWNGYYDTHDLDY, residues 99-115 of SEQ ID NO;

367 (CDR-H3),

DPNEFWNGYYDTHHFDY, residues 99-115 of SEQ ID NO;

368 (CDR-H3),

VPNEFWNGYYATDYFDN, residues 99-115 of SEQ ID NO;

372 (CDR-H3),

EPNEFWNGYYTTHDFDS, residues 99-115 of SEQ ID NO;

373 (CDR-H3),

VPNEFWNGYYATQDFDY, residues 99-115 of SEQ ID NO;

375 (CDR-H3),

VPNEFWNGYYATDYFDY, residues 99-115 of SEQ ID NO;

376 (CDR-H3),

EPNEFWNGYYSTHDFDY, residues 99-115 of SEQ ID NO;

378 (CDR-H3),

EPNEFWNGYYATHDFDY, residues 99-115 of SEQ ID NO;

379 (CDR-H3),

EPNEFWNGYYTTHDFDA, residues 99-115 of SEQ ID NO;

381 (CDR-H3),

DPHEFWNGYYATHDFDY, residues 99-115 of SEQ ID NO;

384 (CDR-H3),

DPNEFWNGYYSTHDFDS, residues 99-115 of SEQ ID NO;

389 (CDR-H3),

EPNEFWNGYFATNDFDY, residues 99-115 of SEQ ID NO;

402 (CDR-H3),

EPNDFWNGYYDTHDFDS, residues 99-115 of SEQ ID NO;

403 (CDR-H3),

ESSEFWNGYYCTQDFDL, residues 99-115 of SEQ ID NO;

406 (CDR-H3),

ESSEFWNGYYVTNDFDY, residues 99-115 of SEQ ID NO;

409 (CDR-H3),

ESNEFWNGYYPTLDLDS, residues 99-115 of SEQ ID NO;

410 (CDR-H3),

ESNEFWNGYYPTQDYDF, residues 99-115 of SEQ ID NO;

411 (CDR-H3),

ESSAFWNGYYNTNDLDY, residues 99-115 of SEQ ID NO;

412 (CDR-H3),

ESTEFWNGYYNTNDYDN, residues 99-115 of SEQ ID NO;

413 (CDR-H3),

ESNDFWNGYYTTDDFDY, residues 99-115 of SEQ ID NO;

414 (CDR-H3),

ESNDFWNGYYTTDDLDY, residues 99-115 of SEQ ID NO;

415 (CDR-H3),

ESNDFWNGYYTTDDFDC, residues 99-115 of SEQ ID NO;

416 (CDR-H3),

VPNEFWNGYFPTQDFDY, residues 99-115 of SEQ ID NO;

417 (CDR-H3),

ETNEFWNGYFPTQDFDY, residues 99-115 of SEQ ID NO;

418 (CDR-H3),

EPNEFWNGYFPTQDFDY, residues 99-115 of SEQ ID NO;

419 (CDR-H3),

EPNEFWNGYFPTLDFDC, residues 99-115 of SEQ ID NO;

420 (CDR-H3),

EPNDFWNGYYATDNFDY, residues 99-115 of SEQ ID NO;

422 (CDR-H3),

EPNDFWNGYYSTDHFDC, residues 99-115 of SEQ ID NO;

423 (CDR-H3),

VPNDFWNGYFATDYFDD, residues 99-115 of SEQ ID NO;

424 (CDR-H3),

EPNDFWNGYFATDHFDF, residues 99-115 of SEQ ID NO;

425 (CDR-H3),

EPNDFWNGYYDTDHFDY, residues 99-115 of SEQ ID NO;

426 (CDR-H3),

DPNEFWNGYYATHDFDH, residues 99-115 of SEQ ID NO;

427 (CDR-H3),

EPNEFWNGYYSTDHFDY, residues 99-115 of SEQ ID NO;

428 (CDR-H3),

EPNDFWNGYYTTHHFDY, residues 99-115 of SEQ ID NO;

429 (CDR-H3),

RASQIIGSELH, residues 24-34 of SEQ ID NO;

473 (CDR-L1),

RASQDIGSELH, residues 24-34 of SEQ ID NO;

474 (CDR-L1),

RASQNIGSELH, residues 24-34 of SEQ ID NO;

477 (CDR-L1),

RASQNIGSALH, residues 24-34 of SEQ ID NO;

479 (CDR-L1),

RASQDIGSALH, residues 24-34 of SEQ ID NO;

488 (CDR-L1),

RASQDIGAALH, residues 24-34 of SEQ ID NO;

491 (CDR-L1),

RASQNIGSSLH, residues 24-34 of SEQ ID NO;

492 (CDR-L1),

RASQDIGYELH, residues 24-34 of SEQ ID NO;

497 (CDR-L1),

RASQEIGFALH, residues 24-34 of SEQ ID NO;

499 (CDR-L1),

RASQNIGAELH, residues 24-34 of SEQ ID NO;

500 (CDR-L1),

RASQDIGSGLH, residues 24-34 of SEQ ID NO;

505 (CDR-L1),

RASQDIGSDLH, residues 24-34 of SEQ ID NO;

506 (CDR-L1),

RASQDIDSDLH, residues 24-34 of SEQ ID NO;

507 (CDR-L1),

RASQDIGEALH, residues 24-34 of SEQ ID NO;

516 (CDR-L1),

RASQEIGASLH, residues 24-34 of SEQ ID NO;

517 (CDR-L1),

RASQDIGGELH, residues 24-34 of SEQ ID NO;

518 (CDR-L1),

RASQDIETELH, residues 24-34 of SEQ ID NO;

519 (CDR-L1),

RASQNIGSDLH, residues 24-34 of SEQ ID NO;

520 (CDR-L1),

RASQNIGYELH, residues 24-34 of SEQ ID NO;

521 (CDR-L1),

RASQNIGTELH, residues 24-34 of SEQ ID NO;

522 (CDR-L1),

RASQNIGSGLH, residues 24-34 of SEQ ID NO;

530 (CDR-L1),

RASQNIDSELH, residues 24-34 of SEQ ID NO;

533 (CDR-L1),

RASQNIDSDLH, residues 24-34 of SEQ ID NO;

535 (CDR-L1),

RASQNIGEELH, residues 24-34 of SEQ ID NO;

537 (CDR-L1),

RASQAIGSELH, residues 24-34 of SEQ ID NO;

539 (CDR-L1),

YASHSIS, residues 50-56 of SEQ ID NO;

473 (CDR-L2),

YASHSGS, residues 50-56 of SEQ ID NO;

476 (CDR-L2),

YASWSQS, residues 50-56 of SEQ ID NO;

477 (CDR-L2),

YASNSIS, residues 50-56 of SEQ ID NO;

478 (CDR-L2),

YASQSIS, residues 50-56 of SEQ ID NO;

479 (CDR-L2),

YASHSVS, residues 50-56 of SEQ ID NO;

489 (CDR-L2),

YASYSVS, residues 50-56 of SEQ ID NO;

490 (CDR-L2),

YASHSNP, residues 50-56 of SEQ ID NO;

491 (CDR-L2),

YASYPIS, residues 50-56 of SEQ ID NO;

493 (CDR-L2),

YASHSNS, residues 50-56 of SEQ ID NO;

495 (CDR-L2),

YASESMS, residues 50-56 of SEQ ID NO;

496 (CDR-L2),

YASYSSS, residues 50-56 of SEQ ID NO;

498 (CDR-L2),

YASHSTS, residues 50-56 of SEQ ID NO;

502 (CDR-L2),

YASHSMS, residues 50-56 of SEQ ID NO;

504 (CDR-L2),

YASYSTS, residues 50-56 of SEQ ID NO;

509 (CDR-L2),

YASESIS, residues 50-56 of SEQ ID NO;

510 (CDR-L2),

YASHSAS, residues 50-56 of SEQ ID NO;

511 (CDR-L2),

YASESGS, residues 50-56 of SEQ ID NO;

513 (CDR-L2),

YASSSTS, residues 50-56 of SEQ ID NO;

514 (CDR-L2),

YASSSLS, residues 50-56 of SEQ ID NO;

515 (CDR-L2),

YASHCIS, residues 50-56 of SEQ ID NO;

522 (CDR-L2),

YASESVS, residues 50-56 of SEQ ID NO;

524 (CDR-L2),

YASYSIS, residues 50-56 of SEQ ID NO;

530 (CDR-L2),

YASSSIS, residues 50-56 of SEQ ID NO;

532 (CDR-L2),

YASSSPS, residues 50-56 of SEQ ID NO;

537 (CDR-L2),

HQSYDLPHT, residues 89-97 of SEQ ID NO;

473 (CDR-L3),

HQSYDLPYT, residues 89-97 of SEQ ID NO;

474 (CDR-L3),

HQSYWLPNT, residues 89-97 of SEQ ID NO;

475 (CDR-L3),

HQSYNLPIT, residues 89-97 of SEQ ID NO;

476 (CDR-L3),

HQSMSLPHT, residues 89-97 of SEQ ID NO;

478 (CDR-L3),

HQSTSLPHT, residues 89-97 of SEQ ID NO;

479 (CDR-L3),

HQGTSLPHT, residues 89-97 of SEQ ID NO;

486 (CDR-L3),

HQSDILPHT, residues 89-97 of SEQ ID NO;

489 (CDR-L3),

HQSDILPQT, residues 89-97 of SEQ ID NO;

491 (CDR-L3),

HQSDFLPHT, residues 89-97 of SEQ ID NO;

492 (CDR-L3),

HQSDDLPYT, residues 89-97 of SEQ ID NO;

494 (CDR-L3),

HQSSWLPHT, residues 89-97 of SEQ ID NO;

495 (CDR-L3),

HQSS#LPHS, residues 89-97 of SEQ ID NO;

496 (CDR-L3),

HQSSELPHT, residues 89-97 of SEQ ID NO;

497 (CDR-L3),

HQSSCLPHT, residues 89-97 of SEQ ID NO;

498 (CDR-L3),

HQTEELPYT, residues 89-97 of SEQ ID NO;

499 (CDR-L3),

HQTDRLPYS, residues 89-97 of SEQ ID NO;

500 (CDR-L3),

HQTFSLPYT, residues 89-97 of SEQ ID NO;

501 (CDR-L3),

HQTDSLPYT, residues 89-97 of SEQ ID NO;

502 (CDR-L3),

HQTSDLPYT, residues 89-97 of SEQ ID NO;

503 (CDR-L3),

HQTNSLPYT, residues 89-97 of SEQ ID NO;

504 (CDR-L3),

HQTDWLPYT, residues 89-97 of SEQ ID NO;

505 (CDR-L3),

HQTFNLPYT, residues 89-97 of SEQ ID NO;

507 (CDR-L3),

HQTAYLPQT, residues 89-97 of SEQ ID NO;

508 (CDR-L3),

HQTDGLPYT, residues 89-97 of SEQ ID NO;

509 (CDR-L3),

HQTTLLPYT, residues 89-97 of SEQ ID NO;

511 (CDR-L3),

HQGFSLPHT, residues 89-97 of SEQ ID NO;

512 (CDR-L3),

HQSFCLPYT, residues 89-97 of SEQ ID NO;

513 (CDR-L3),

HQSTSLPYT, residues 89-97 of SEQ ID NO;

514 (CDR-L3),

HQSDYLPYT, residues 89-97 of SEQ ID NO;

515 (CDR-L3),

HQSDWLPYT, residues 89-97 of SEQ ID NO;

516 (CDR-L3),

HQSDGLPYT, residues 89-97 of SEQ ID NO;

517 (CDR-L3),

HQSNDLPYT, residues 89-97 of SEQ ID NO;

518 (CDR-L3),

HQTYGLPYT, residues 89-97 of SEQ ID NO;

519 (CDR-L3),

HQSMGLPYT, residues 89-97 of SEQ ID NO;

520 (CDR-L3),

HQSFTLPYT, residues 89-97 of SEQ ID NO;

521 (CDR-L3),

HQSESLPHT, residues 89-97 of SEQ ID NO;

522 (CDR-L3),

HQSDTLPHT, residues 89-97 of SEQ ID NO;

523 (CDR-L3),

HQSTNLPYT, residues 89-97 of SEQ ID NO;

524 (CDR-L3),

HQSSILPHT, residues 89-97 of SEQ ID NO;

525 (CDR-L3),

HQSTWLPYT, residues 89-97 of SEQ ID NO;

526 (CDR-L3),

HQSAFLPYI, residues 89-97 of SEQ ID NO;

527 (CDR-L3),

HQSISLPQT, residues 89-97 of SEQ ID NO;

528 (CDR-L3),

HQSASLPIT, residues 89-97 of SEQ ID NO;

529 (CDR-L3),

HQSAYLPYT, residues 89-97 of SEQ ID NO;

530 (CDR-L3),

HQSAVLPDT, residues 89-97 of SEQ ID NO;

531 (CDR-L3),

HQSSDLPYT, residues 89-97 of SEQ ID NO;

532 (CDR-L3),

HQSFSLPYT, residues 89-97 of SEQ ID NO;

533 (CDR-L3),

HQSAFLPYT, residues 89-97 of SEQ ID NO;

534 (CDR-L3),

HQSYSLPFN, residues 89-97 of SEQ ID NO;

535 (CDR-L3),

HQSYMLPYS, residues 89-97 of SEQ ID NO;

536 (CDR-L3),

HQSFSLPVT, residues 89-97 of SEQ ID NO;

537 (CDR-L3),

HQSISLPYT, residues 89-97 of SEQ ID NO;

538 (CDR-L3),

And

HQSASLPYT, residues 89-97 of SEQ ID NO;

539 (CDR-L3).

3. The antibody or antigen binding portion thereof according to claim 1, wherein the antigen binding domain comprises a heavy chain variable region (VH) comprising an amino acid sequence selected from the group consisting of SEQ ID NO:

46 and SEQ ID NOS;

359-472.

4. The antibody or antigen binding portion thereof according to claim 1, wherein the antigen binding domain comprises a light chain variable region (VL) comprising an amino acid sequence selected from the group consisting of SEQ ID NO:

47, SEQ ID NO;

553, and SEQ ID NOS;

473-539.

5. The antibody or antigen binding portion thereof according to claim 1, further comprising a heavy chain immunoglobulin constant domain comprising 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, or a human IgA constant domain.

6. The antibody or antigen binding portion thereof according to claim 5, wherein the heavy chain immunoglobulin constant domain is the human IgG1 constant domain.

7. The antibody or antigen binding portion thereof according to claim 6, wherein the human IgG1 constant domain comprises the amino acid sequence of SEQ ID NO:

3 or SEQ ID NO;

4.

8. The antibody or antigen binding portion thereof according to claim 1, further comprising a light chain immunoglobulin constant domain comprising a human Ig kappa constant domain or a human Ig lambda constant domain.

9. The antibody or antigen binding portion thereof according to claim 8, wherein the human Ig kappa constant domain comprises the amino acid sequence of SEQ ID NO:

5.

10. The antibody or antigen binding portion thereof according to claim 8, wherein the human Ig lambda constant domain comprises the amino acid sequence of SEQ ID NO:

6.

11. The antibody or antigen binding portion thereof according to claim 1, wherein the antibody or antigen binding portion thereof is an immunoglobulin molecule, an scFv, a monoclonal antibody, a human antibody, a humanized antibody, an affinity matured antibody, a chimeric antibody, a Fab fragment, an Fab′

fragment, an F(ab′

)₂, an Fv, or a disulfide linked Fv.

12. The antibody or antigen binding portion thereof according to claim 11, wherein the antibody or antigen binding portion thereof is a human antibody.

13. The antibody or antigen binding portion thereof according to claim 1, wherein the antibody or antigen binding portion thereof is capable of causing an increase or decrease in the magnitude of a biological function of IL-17, compared to the magnitude of the biological function of IL-17 observed in the absence of the antibody or antigen binding portion thereof.

14. The antibody or antigen binding portion thereof according to claim 1, wherein the antibody or antigen binding portion thereof neutralizes a biological function of IL-17.

15. The antibody or antigen binding portion thereof according to claim 13, wherein the IL-17 is pro-human IL-17, mature-human IL-17, or truncated-human IL-17.

16. The antibody or antigen binding portion thereof according to claim 14, wherein the antibody or antigen binding portion thereof diminishes the ability of IL-17 to bind to its receptor.

17. The antibody or antigen binding portion thereof according to claim 16, wherein the IL-17 is pro-human IL-17, mature-human IL-17, or truncated-human IL-17.

18. The antibody or antigen binding portion thereof according to claim 13, wherein the antibody or antigen binding portion thereof has a dissociation constant (K_D) of at most about 10⁻

7 M.

19. The antibody or antigen binding portion thereof according to claim 13, wherein the antibody or antigen binding portion thereof has an on rate constant (K_on) of at least about 10²M⁻

1s<sup>−

1</sup>.

20. The antibody or antigen binding portion thereof according to claim 13, wherein the antibody or antigen binding portion thereof has an off rate (K_off) of at most about 10⁻

3s<sup>−

1</sup>.

21. The antibody or antigen binding portion thereof according to claim 1, wherein the antibody or antigen binding portion thereof is conjugated to a detectable label.

22. The antibody or antigen binding portion thereof according to claim 21, wherein the detectable label is selected from the group consisting of a radiolabel, an enzyme, a fluorescent label, a luminescent label, a bioluminescent label, a magnetic label, and a biotin.

23. The antibody or antigen binding portion thereof according to claim 1, wherein the antibody or antigen binding portion thereof is conjugated to a therapeutic or cytotoxic agent.

24. The antibody or antigen binding portion thereof according to claim 23, wherein the 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, a toxin, and an apoptotic agent.

25. The antibody or antigen binding portion thereof according to claim 1, wherein the antibody or antigen binding portion thereof is crystallized.

26. The crystallized antibody or antigen binding portion thereof according to claim 25, wherein the crystallized antibody or antigen binding portion thereof is a carrier-free pharmaceutical controlled release crystal.

27. A composition for the release of a crystallized antibody or antigen binding portion thereof that binds IL-17, the composition comprising:

(a) a formulation, wherein the formulation comprises a crystallized antibody or antigen binding portion thereof according to claim 25 and optionally an additional ingredient comprising an agent selected from the group consisting of albumin, sucrose, trehalose, lactitol, gelatin, hydroxypropyl-β

-cyclodextrin, methoxypolyethylene glycol, and polyethylene glycol; and

(b) at least one polymeric carrier.

28. The composition according to claim 27, wherein the polymeric carrier comprises one or more polymers selected from the group consisting of a poly(acrylic acid), a poly(cyanoacrylate), a poly(amino acid), a poly(anhydride), a poly(depsipeptide), a poly(ester), a poly(lactic acid), a poly(lactic-co-glycolic acid) or PLGA, a poly(b-hydroxybutryate), a poly(caprolactone), a poly(dioxanone);

a poly(ethylene glycol), a poly((hydroxypropyl)methacrylamide, a poly[(organo)phosphazene], a poly(ortho ester), a poly(vinyl alcohol), a poly(vinylpyrrolidone), a maleic anhydride-alkyl vinyl ether copolymer, a pluronic polyol, an albumin, an alginate, a cellulose, a cellulose derivative, a collagen, a fibrin, a gelatin, a hyaluronic acid, an oligosaccharide, a glycaminoglycan, a sulfated polysaccharide, and a blend and a copolymer thereof.

29. A pharmaceutical composition comprising the antibody or antigen binding portion thereof according to claim 1, and a pharmaceutically acceptable carrier.

30. The pharmaceutical composition according to claim 29, further comprising at least one additional therapeutic agent for treating a disorder in which IL-17 activity is detrimental.

31. The pharmaceutical composition according to claim 30, wherein the additional agent is selected from the group consisting of an angiogenesis inhibitor, a kinase inhibitor, a co-stimulation molecule blocker, an adhesion molecule blocker, an anti-cytokine antibody or functional binding fragment thereof, methotrexate, a corticosteroid, a cyclosporine, a rapamycin, FK506, and a non-steroidal anti-inflammatory agent.

32. The antibody or antigen binding portion thereof according to claim 1, wherein antigen binding domain comprises six CDRs:

CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR-L3, wherein;

CDR-H1 has an amino acid sequence S-Y-G-I-S (residues 31-35 of SEQ ID NO;

46) or a modification of said amino acid sequence by substitution of at least one amino acid residue, wherein;

the substitution of S at position 1 is selected from the group consisting of G and T;

the substitution of I at position 4 is selected from the group consisting of F, T, and Y; and

the substitution of S at position 5 is selected from the group consisting of G and

N;

CDR-H2 has an amino acid sequence G-I-T-P-I-L-G-T-A-N-Y-A-Q-K-F-Q-G (residues 50-66 of SEQ ID NO;

46) or a modification of said amino acid sequence by substitution of at least one amino acid residue, wherein;

the substitution of P at position 4 is selected from the group consisting of H and N;

the substitution of I at position 5 is F;

the substitution of L at position 6 is F;

the substitution of T at position 8 is selected from the group consisting of I, S, W, A, F, and L;

the substitution of A at position 9 is selected from the group consisting of T and V; and

the substitution of N at position 10 is D;

CDR-H3 has an amino acid sequence;

E-P-N-D-F-W-N-G-Y-Y-T-T-H-H-F-D-Y (residues 99-115 of SEQ ID NO;

46) or a modification of said amino acid sequence by substitution of at least one amino acid residue, wherein;

the substitution of E at position 1 is selected from the group consisting of D and V;

the substitution of P at position 2 is S;

the substitution of N at position 3 is S;

the substitution of D at position 4 is E; and

the substitution of T at position 11 is selected from the group consisting of A, S, D, and C;

CDR-L1 has an amino acid sequence;

R-A-S-Q-N-I-G-S-A-L-H (residues 24-34 of SEQ ID NO;

47) or a modification of said amino acid sequence by substitution of at least one amino acid residue, wherein;

the substitution of N at position 5 is selected from the group consisting of D, E, and A;

the substitution of S at position 8 is A and

the substitution of A at position 9 is selected from the group consisting of E, D, and S;

CDR-L2 has an amino acid sequence;

Y-A-S-Q-S-I-S (residues 50-56 of SEQ ID NO;

47) or a modification of said amino acid sequence by substitution of at least one amino acid residue, wherein;

the substitution of Q at position 4 is selected from the group consisting of H, Y, and N; and

the substitution of I at position 6 is selected from the group consisting of V, T, and A; and

CDR-L3 has an amino acid sequence;

H-Q-S-T-S-L-P-H-T (residues 89-97 of SEQ ID NO;

47) or a modification of said amino acid sequence by substitution of at least one amino acid residue, wherein;

the substitution of S at position 3 is T;

the substitution of T at position 4 is selected from the group consisting of D and A;

the substitution of S at position 5 is selected from the group consisting of G, I, T, Y, and R;

the substitution of H at position 8 is selected from the group consisting of Y and Q; and

the substitution of T at position 9 is S; and

wherein said substitution of at least one amino acid residue does not inhibit the ability of said antibody or antigen binding portion thereof to bind human IL-17.

33. The antibody or antigen binding portion thereof according to claim 32, wherein the CDRs are selected from the group consisting of:

SYGIS, residues 31-35 of SEQ ID NO;

359 (CDR-H1),

GYGIS, residues 31-35 of SEQ ID NO;

368 (CDR-H1),

TYGIS, residues 31-35 of SEQ ID NO;

372 (CDR-H1),

GYGTS, residues 31-35 of SEQ ID NO;

383 (CDR-H1),

GYGIG, residues 31-35 of SEQ ID NO;

389 (CDR-H1),

SYGFS, residues 31-35 of SEQ ID NO;

405 (CDR-H1),

SYGYN, residues 31-35 of SEQ ID NO;

406 (CDR-H1),

GITNFFGWTDYAQKFQG, residues 50-66 of SEQ ID NO;

360 (CDR-H2),

GITPFFGWADYAQKFQG, residues 50-66 of SEQ ID NO;

368 (CDR-H2),

GITHFFGSTDYAQKFQG, residues 50-66 of SEQ ID NO;

374 (CDR-H2),

GITHFFGAVDYAQKFQG, residues 50-66 of SEQ ID NO;

383 (CDR-H2),

GITPFFGFADYAQKFQG, residues 50-66 of SEQ ID NO;

389 (CDR-H2),

GITHFFGITDYAQKFQG, residues 50-66 of SEQ ID NO;

403 (CDR-H2),

GITPFFGTADYAQKFQG, residues 50-66 of SEQ ID NO;

406 (CDR-H2),

GITPFFGLADYAQKFQG, residues 50-66 of SEQ ID NO;

407 (CDR-H2),

GITPILGTANYAQKFQG, residues 50-66 of SEQ ID NO;

410 (CDR-H2),

DPNEFWNGYYATHDFDY, residues 99-115 of SEQ ID NO;

359 (CDR-H3),

DPNEFWNGYYDTHHFDY, residues 99-115 of SEQ ID NO;

368 (CDR-H3),

VPNEFWNGYYATDYFDN, residues 99-115 of SEQ ID NO;

372 (CDR-H3),

EPNEFWNGYYTTHDFDS, residues 99-115 of SEQ ID NO;

373 (CDR-H3),

DPNEFWNGYYSTHDFDS, residues 99-115 of SEQ ID NO;

389 (CDR-H3),

EPNDFWNGYYDTHDFDS, residues 99-115 of SEQ ID NO;

403 (CDR-H3),

ESSEFWNGYYCTQDFDL, residues 99-115 of SEQ ID NO;

406 (CDR-H3),

EPNDFWNGYYTTHHFDY, residues 99-115 of SEQ ID NO;

429 (CDR-H3),

RASQDIGSELH, residues 24-34 of SEQ ID NO;

474 (CDR-L1),

RASQNIGSELH, residues 24-34 of SEQ ID NO;

477 (CDR-L1),

RASQNIGSALH, residues 24-34 of SEQ ID NO;

479 (CDR-L1),

RASQDIGSALH, residues 24-34 of SEQ ID NO;

488 (CDR-L1),

RASQNIGAELH, residues 24-34 of SEQ ID NO;

500 (CDR-L1),

RASQDIGSDLH, residues 24-34 of SEQ ID NO;

506 (CDR-L1),

RASQEIGASLH, residues 24-34 of SEQ ID NO;

517 (CDR-L1),

RASQAIGSELH, residues 24-34 of SEQ ID NO;

539 (CDR-L1),

YASHSIS, residues 50-56 of SEQ ID NO;

473 (CDR-L2),

YASNSIS, residues 50-56 of SEQ ID NO;

478 (CDR-L2),

YASQSIS, residues 50-56 of SEQ ID NO;

479 (CDR-L2),

YASHSVS, residues 50-56 of SEQ ID NO;

489 (CDR-L2),

YASYSVS, residues 50-56 of SEQ ID NO;

490 (CDR-L2),

YASHSTS, residues 50-56 of SEQ ID NO;

502 (CDR-L2),

YASHSAS, residues 50-56 of SEQ ID NO;

511 (CDR-L2),

HQSTSLPHT, residues 89-97 of SEQ ID NO;

479 (CDR-L3),

HQSDILPHT, residues 89-97 of SEQ ID NO;

489 (CDR-L3),

HQTDRLPYS, residues 89-97 of SEQ ID NO;

500 (CDR-L3),

HQTDSLPYT, residues 89-97 of SEQ ID NO;

502 (CDR-L3),

HQTAYLPQT, residues 89-97 of SEQ ID NO;

508 (CDR-L3),

HQSDGLPYT, residues 89-97 of SEQ ID NO;

517 (CDR-L3),

HQSDTLPHT, residues 89-97 of SEQ ID NO;

523 (CDR-L3),

And

HQSASLPYT, residues 89-97 of SEQ ID NO;

539 (CDR-L3).

34. The antibody or antigen binding portion thereof according to claim 32, wherein the antigen binding domain comprises a heavy chain variable region (VH) comprising an amino acid sequence selected from the group consisting of:

SEQ ID NOS;

368, 372, 377, 383, 389, 403, 407, 454, and 455.

35. The antibody or antigen binding portion thereof according to claim 32, wherein the antigen binding domain comprises a light chain variable region (VL) comprising an amino acid sequence selected from the group consisting of:

SEQ ID NOS;

47, 489, 500, 508, 517, 523, 539, and 553.

36. The antibody or antigen binding portion thereof according to claim 32, wherein the antigen binding domain comprises a heavy chain variable region (VH) comprising three CDRs from SEQ ID NO:

368 or the amino acid sequence of SEQ ID NO;

368.

37. The antibody or antigen binding portion thereof according to claim 32, wherein the antigen binding domain comprises a heavy chain variable region (VH) comprising three CDRs from SEQ ID NO:

372 or the amino acid sequence of SEQ ID NO;

372.

38. The antibody or antigen binding portion thereof according to claim 32, wherein the antigen binding domain comprises a heavy chain variable region (VH) comprising three CDRs from SEQ ID NO:

377 or the amino acid sequence of SEQ ID NO;

377.

39. The antibody or antigen binding portion thereof according to claim 32, wherein the antigen binding domain comprises a heavy chain variable region (VH) comprising three CDRs from SEQ ID NO:

383 or the amino acid sequence of SEQ ID NO;

383.

40. The antibody or antigen binding portion thereof according to claim 32, wherein the antigen binding domain comprises a heavy chain variable region (VH) comprising three CDRs from SEQ ID NO:

389 or the amino acid sequence of SEQ ID NO;

389.

41. The antibody or antigen binding portion thereof according to claim 32, wherein the antigen binding domain comprises a heavy chain variable region (VH) comprising three CDRs from SEQ ID NO:

403 or the amino acid sequence of SEQ ID NO;

403.

42. The antibody or antigen binding portion thereof according to claim 32, wherein the antigen binding domain comprises a heavy chain variable region (VH) comprising three CDRs from SEQ ID NO:

407 or the amino acid sequence of SEQ ID NO;

407.

43. The antibody or antigen binding portion thereof according to claim 32, wherein the antigen binding domain comprises a heavy chain variable region (VH) comprising three CDRs from SEQ ID NO:

454 or the amino acid sequence of SEQ ID NO;

454.

44. The antibody or antigen binding portion thereof according to claim 32, wherein the antigen binding domain comprises a heavy chain variable region (VH) comprising three CDRs from SEQ ID NO:

455 or the amino acid sequence of SEQ ID NO;

455.

45. The antibody or antigen binding portion thereof according to claim 32, wherein the antigen binding domain comprises a light chain variable region (VL) comprising three CDRs from SEQ ID NO:

47 or the amino acid sequence of SEQ ID NO;

47.

46. The antibody or antigen binding portion thereof according to claim 32, wherein the antigen binding domain comprises a light chain variable region (VL) comprising three CDRs from SEQ ID NO:

489 or the amino acid sequence of SEQ ID NO;

489.

47. The antibody or antigen binding portion thereof according to claim 32, wherein the antigen binding domain comprises a light chain variable region (VL) comprising three CDRs from SEQ ID NO:

500 or the amino acid sequence of SEQ ID NO;

500.

48. The antibody or antigen binding portion thereof according to claim 32, wherein the antigen binding domain comprises a light chain variable region (VL) comprising three CDRs from SEQ ID NO:

508 or the amino acid sequence of SEQ ID NO;

508.

49. The antibody or antigen binding portion thereof according to claim 32, wherein the antigen binding domain comprises a light chain variable region (VL) comprising three CDRs from SEQ ID NO:

517 or the amino acid sequence of SEQ ID NO;

517.

50. The antibody or antigen binding portion thereof according to claim 32, wherein the antigen binding domain comprises a light chain variable region (VL) comprising three CDRs from SEQ ID NO:

523 or the amino acid sequence of SEQ ID NO;

523.

51. The antibody or antigen binding portion thereof according to claim 32, wherein the antigen binding domain comprises a light chain variable region (VL) comprising three CDRs from SEQ ID NO:

539 or the amino acid sequence of SEQ ID NO;

539.

52. The antibody or antigen binding portion thereof according to claim 32, wherein the antigen binding domain comprises a light chain variable region (VL) comprising three CDRs from SEQ ID NO:

553 or the amino acid sequence of SEQ ID NO;

553.

53. The antibody or antigen binding portion thereof according to claim 32, wherein the antigen binding domain comprises

a heavy chain variable region (VH) comprising three CDRs from SEQ ID NO:

403 or the amino acid sequence of SEQ ID NO;

403; and

a light chain variable region (VL) comprising three CDRs from SEQ ID NO;

523 or the amino acid sequence of SEQ ID NO;

523.

54. The antibody or antigen binding portion thereof according to claim 32, wherein the antigen binding domain comprises

a heavy chain variable region (VH) comprising three CDRs from SEQ ID NO:

383 or the amino acid sequence of SEQ ID NO;

383; and

a light chain variable region (VL) comprising three CDRs from SEQ ID NO;

500 or the amino acid sequence of SEQ ID NO;

500.

55. The antibody or antigen binding portion thereof according to claim 32, wherein the antigen binding domain comprises

a heavy chain variable region (VH) comprising three CDRs from SEQ ID NO:

368 or the amino acid sequence of SEQ ID NO;

368; and

a light chain variable region (VL) comprising three CDRs from SEQ ID NO;

489 or the amino acid sequence of SEQ ID NO;

489.

56. The antibody or antigen binding portion thereof according to claim 32, wherein the antigen binding domain comprises

a heavy chain variable region (VH) comprising three CDRs from SEQ ID NO:

389 or the amino acid sequence of SEQ ID NO;

389; and

a light chain variable region (VL) comprising three CDRs from SEQ ID NO;

553 or the amino acid sequence of SEQ ID NO;

553.

57. The antibody or antigen binding portion thereof according to claim 32, wherein the antigen binding domain comprises

a heavy chain variable region (VH) comprising three CDRs from SEQ ID NO:

372 or the amino acid sequence of SEQ ID NO;

372; and

a light chain variable region (VL) comprising three CDRs from SEQ ID NO;

517 or the amino acid sequence of SEQ ID NO;

517.

58. The antibody or antigen binding portion thereof according to claim 32, wherein the antigen binding domain comprises

a heavy chain variable region (VH) comprising three CDRs from SEQ ID NO:

377 or the amino acid sequence of SEQ ID NO;

377; and

a light chain variable region (VL) comprising three CDRs from SEQ ID NO;

539 or the amino acid sequence of SEQ ID NO;

539.

59. The antibody or antigen binding portion thereof according to claim 32, wherein the antigen binding domain comprises

a heavy chain variable region (VH) comprising three CDRs from SEQ ID NO:

407 or the amino acid sequence of SEQ ID NO;

407; and

a light chain variable region (VL) comprising three CDRs from SEQ ID NO;

508 or the amino acid sequence of SEQ ID NO;

508.

60. The antibody or antigen binding portion thereof according to claim 32, wherein the antigen binding domain comprises

a heavy chain variable region (VH) comprising three CDRs from SEQ ID NO:

455 or the amino acid sequence of SEQ ID NO;

455; and

a light chain variable region (VL) comprising three CDRs from SEQ ID NO;

47 or the amino acid sequence of SEQ ID NO;

47.

61. The antibody or antigen binding portion thereof according to claim 32, wherein the antigen binding domain comprises

a heavy chain variable region (VH) comprising three CDRs from SEQ ID NO:

454 or the amino acid sequence of SEQ ID NO;

454; and

a light chain variable region (VL) comprising three CDRs from SEQ ID NO;

47 or the amino acid sequence of SEQ ID NO;

47.

62. The antibody or antigen binding portion thereof according to claim 32, further comprising a heavy chain immunoglobulin constant domain, wherein the heavy chain immunoglobulin constant domain comprises the amino acid sequence of SEQ ID NO:

3 or SEQ ID NO;

4.

63. The antibody or antigen binding portion thereof according to claim 32, further comprising a human Ig kappa constant domain, wherein the human Ig kappa constant domain comprises the amino acid sequence of SEQ ID NO:

5.

64. The antibody or antigen binding portion thereof according to claim 32, further comprising a human Ig lambda constant domain, wherein the human Ig lambda constant domain comprises the amino acid sequence of SEQ ID NO:

6.