Claims for Patent: 9,409,986

Summary for Patent: 9,409,986

Title:	IL-1 binding proteins
Abstract:	Proteins that bind IL-1.alpha. and IL-1.beta. are described along with their use in compositions and methods for treating, preventing, and diagnosing IL-1-related disorders and for detecting IL-1.alpha. and IL-1.beta. in cells, tissues, samples, and compositions.
Inventor(s):	Wu; Chengbin (Shanghai, CN), Ambrosi; Dominic J. (Shrewsbury, MA), Hsieh; Chung-ming (Newton, MA), Ghayur; Tariq (Holliston, MA)
Assignee:	AbbVie Inc. (North Chicago, IL)
Application Number:	14/133,380
Patent Claims:	1. A method for reducing human IL-1 activity in a human subject in need thereof, comprising administering to the human subject a binding protein, wherein the binding protein comprises an antigen binding domain, said binding protein capable of binding human IL-1.beta., said antigen binding domain comprising six CDRs: CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR-L3, as defined below: CDR-H1: X.sub.1-Y-D-M-S (SEQ ID NO:190), wherein; X.sub.1 is, K or R; CDR-H2: Y-X.sub.2-S-X.sub.4-G-G-X.sub.7-G-T-Y-Y-P-D-X.sub.14-X.sub.15-K-G (SEQ ID NO:191), wherein; X.sub.2 is I or V; X.sub.4 is S or H; X.sub.7 is G or A; X.sub.14 is T or S; and X.sub.15 is V or A; CDR-H3: G-G-V-X.sub.4-K-G-X.sub.7-F-D-X.sub.10 (SEQ ID NO:192), wherein; X.sub.4 is T or Y; X.sub.7 is Y or C; and X.sub.10 is V, E, L, M, Q, or Y; CDR-L1: R-A-S-G-N-I-X.sub.7-X.sub.8-X.sub.9-L-X.sub.11 (SEQ ID NO:193), wherein; X.sub.7 is H, Y, or W; X.sub.8 is N, G, T, Q, E, H, D, or K; X.sub.9 is Y or W; and X.sub.11 is T, A, or N; CDR-L2: X.sub.1-A-K-X.sub.4-L-X.sub.6-X.sub.7 (SEQ ID NO:194), wherein; X.sub.1 is N, Q, or D; X.sub.4 is T, N, I, E, or S; X.sub.6 is A, M, or E; and X.sub.7 is D, E, S, or A; and CDR-L3: Q-X.sub.2-F-W-X.sub.5-X.sub.6-P-X.sub.8-X.sub.9 (SEQ ID NO:195), wherein; X.sub.2 is H or Q; X.sub.5 is S, N, T, K, R, or M; X.sub.6 is I or L; X.sub.8 is Y or A; and X.sub.9 is T, I, and N; except that CDR-H2 cannot be Y-I-S-S-G-G-G-G-T-Y-Y-P-D-T-V-K-G (SEQ ID NO:18); CDR-H3 cannot be G-G-V-T-K-G-Y-F-D-V (SEQ ID NO:19); CDR-L1 cannot be R-A-S-G-N-I-H-N-Y-L-T (SEQ ID NO:20); CDR-L2 cannot be N-A-K-T-L-A-D (SEQ ID NO:21); and CDR-L3 cannot be Q-H-F-W-S-I-P-Y-T (SEQ ID NO:22), such that the human IL-1 activity in the human subject suffering from a disorder in which IL-1 activity is detrimental is reduced. 2. The method according to claim 1, wherein administering to the subject is by at least one route selected from the group consisting of: parenteral, subcutaneous, intramuscular, intravenous, intra-articular, intrabronchial, intraabdominal, intracapsular, intracartilaginous, intracavitary, intracelial, intracerebellar, intracerebroventricular, intracolic, intracervical, intragastric, intrahepatic, intramyocardial, intraosteal, intrapelvic, intrapericardiac, intraperitoneal, intrapleural, intraprostatic, intrapulmonary, intrarectal, intrarenal, intraretinal, intraspinal, intrasynovial, intrathoracic, intrauterine, intravesical, bolus, vaginal, rectal, buccal, sublingual, intranasal, and transdermal. 3. The method according to claim 1, further comprising administering at least one additional agent. 4. The method according to claim 3, wherein the at least one additional agent is a therapeutic agent. 5. The method according to claim 4, wherein the therapeutic agent comprises at least one selected from the group consisting of: an inhaled steroid; a beta-agonist; a short-acting beta-agonist; a long-acting beta-agonist; an antagonist of a leukotriene; an antagonist of a leukotriene receptor; ADVAIR.TM.; an IgE inhibitor; an anti-IgE antibody; XOLAIR.TM.; a phosphodiesterase inhibitor; a PDE4 inhibitor; a xanthine; an anticholinergic drug; a mast cell-stabilizing agent; Cromolyn; an IL-4 inhibitor; an IL-5 inhibitor; an eotaxin/CCR3 inhibitor; an antagonist of histamine; an antagonist of histamine receptors including H1, H2, H3, and H4; an antagonists of prostaglandin D; an antagonist of prostaglandin D receptors DP1 and CRTH2; a TNF antagonist; a soluble fragment of a TNF receptor; ENBREL.RTM.; a TNF enzyme antagonist; a TNF converting enzyme (TACE) inhibitor; a muscarinic receptor antagonist; a TGF-beta antagonist; an interferon gamma; a perfenidone; a chemotherapeutic agent, a methotrexate; a leflunomide; a sirolimus (rapamycin) or an analog thereof; CCI-779; a COX2 inhibitor; a cPLA2 inhibitor; a NSAID; an immunomodulator; a p38 inhibitor; a TPL-2 inhibitor; a MK-2 inhibitor; a NFkB inhibitor; budenoside; an epidermal growth factor; a corticosteroid; cyclosporine; sulfasalazine; an aminosalicylate; 6-mercaptopurine; azathioprine; metronidazole; a lipoxygenase inhibitor; mesalamine; olsalazine; balsalazide; an antioxidants; a thromboxane inhibitor; a IL-1 receptor antagonist; an anti-IL-1.beta. antibody; an anti-IL-6 antibody; a growth factor; an elastase inhibitor; a pyridinyl-imidazole compound; an antibody or agonist of TNF, LT, IL-1, IL-2, IL-3, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-11, IL-12, IL-14, IL-15, IL-16, IL-17, IL-18, IL-19, IL-20, IL-21, IL-22, IL-23, IL-24, IL-25, IL-26, IL-27, IL-28, IL-29, IL-30, IL-31, IL-32, IL-33, EMAP-II, GM-CSF, FGF, or PDGF; an antibody of CD2, CD3, CD4, CD8, CD25, CD28, CD30, CD40, CD45, CD69, CD90 or their ligands; FK506; rapamycin; mycophenolate mofetil; ibuprofen; prednisolone; a phosphodiesterase inhibitor; an adensosine agonist; an antithrombotic agent; a complement inhibitor; an adrenergic agent; an IRAK inhibitor; a NIK inhibitor; an IKK inhibitor; a p38 inhibitor; a MAP kinase inhibitors; an IL-1.beta. converting enzyme inhibitor; a TNF-.alpha. converting enzyme inhibitor; a T-cell signaling inhibitor; a metalloproteinase inhibitor; a 6-mercaptopurine; an angiotensin converting enzyme inhibitor; a soluble cytokine receptor; a soluble p55 TNF receptor; a soluble p75 TNF receptor; sIL-1RI; sIL-1RII; sIL-6R; an anti-inflammatory cytokine; IL-4; IL-10; IL-11; and TGF-.beta.. 6. The method according to claim 4, wherein the therapeutic agent comprises at least one selected from the group consisting of: methotrexate; 6-MP; azathioprine sulphasalazine; mesalazine; olsalazine chloroquinine/hydroxychloroquine; pencillamine; aurothiomalate; azathioprine; colchicine; a corticosteroid; a beta-2 adrenoreceptor agonists; a xanthine; cromoglycate; nedocromil; ketotifen; ipratropium and oxitropium; cyclosporin; FK506; rapamycin; mycophenolate mofetil; leflunomide; a NSAID; a corticosteroid; a phosphodiesterase inhibitor; an adensosine agonist; an antithrombotic agent; a complement inhibitor; an adrenergic agent; an agent which interferes with IKK; p38 inhibitor; MAP kinase inhibitors; an IL-1.beta. converting enzyme inhibitor; a TNF-.alpha. converting enzyme (TACE) inhibitor; a T-cell signaling inhibitor; metalloproteinase inhibitors; sulfasalazine; azathioprine; a 6-mercaptopurine; an angiotensin converting enzyme inhibitor; a soluble cytokine receptor or derivative thereof; an antiinflammatory cytokine; celecoxib; folic acid; hydroxychloroquine sulfate; etanercept; infliximab; naproxen; valdecoxib; sulfasalazine; methylprednisolone; meloxicam; methylprednisolone acetate; gold sodium thiomalate; aspirin; triamcinolone acetonide; propoxyphene napsylate/apap; folate; nabumetone; diclofenac; piroxicam; etodolac; diclofenac sodium; oxaprozin; oxycodone hcl; hydrocodone bitartrate/apap; diclofenac sodium/misoprostol; fentanyl; anakinra; human recombinant; tramadol hcl; salsalate; sulindac; cyanocobalamin/fa/pyridoxine; acetaminophen; alendronate sodium; prednisolone; morphine sulfate; lidocaine hydrochloride; indomethacin; glucosamine sulf/chondroitin; amitriptyline HCl; sulfadiazine; oxycodone HCl/acetaminophen; olopatadine HCl; misoprostol; naproxen sodium; omeprazole; cyclophosphamide; rituximab; IL-1 TRAP; MRA; CTLA4-IG; IL-18 BP; anti-IL-18; anti-IL15; BIRB-796; SCIO-469; VX-702; AMG-548; VX-740; Roflumilast; IC-485; CDC-801; and Mesopram. 7. The method according to claim 1, comprising CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR-L3 wherein the CDR-H1 is an amino acid selected from the group consisting of residues 31-35 of SEQ ID NO:60; residues 31-35 of SEQ ID NO:61; residues 31-35 of SEQ ID NO:114; and residues 31-35 of SEQ ID NO:117; wherein the CDR-H2 is an amino acid selected from the group consisting of residues 50-66 of SEQ ID NO:60; residues 50-66 of SEQ ID NO:71; residues 50-66 of SEQ ID NO:105; residues 50-66 of SEQ ID NO:113; residues 50-66 of SEQ ID NO:123; residues 50-66 of SEQ ID NO:131; and residues 50-66 of SEQ ID NO:133; wherein the CDR-H3 is an amino acid selected from the group consisting of residues 99-108 of SEQ ID NO:60 (CDR-H3); residues 99-108 of SEQ ID NO:61 (CDR-H3); residues 99-108 of SEQ ID NO:64 (CDR-H3); residues 99-108 of SEQ ID NO:78 (CDR-H3); residues 99-108 of SEQ ID NO:87 (CDR-H3); residues 99-108 of SEQ ID NO:92 (CDR-H3); residues 99-108 of SEQ ID NO:104 (CDR-H3); and residues 99-108 of SEQ ID NO:140 (CDR-H3); wherein the CDR-L1 is an amino acid selected from the group consisting of residues 24-34 of SEQ ID NO:59 (CDR-L1); residues 24-34 of SEQ ID NO:149 (CDR-L1); residues 24-34 of SEQ ID NO:150 (CDR-L1); residues 24-34 of SEQ ID NO:151 (CDR-L1); residues 24-34 of SEQ ID NO:153 (CDR-L1); residues 24-34 of SEQ ID NO:156 (CDR-L1); residues 24-34 of SEQ ID NO:159 (CDR-L1); residues 24-34 of SEQ ID NO:164 (CDR-L1); residues 24-34 of SEQ ID NO:167 (CDR-L1); residues 24-34 of SEQ ID NO:174 (CDR-L1); residues 24-34 of SEQ ID NO:179 (CDR-L1); and residues 24-34 of SEQ ID NO:188 (CDR-L1); wherein the CDR-L2 is an amino acid selected from the group consisting of residues 50-56 of SEQ ID NO:59 (CDR-L2); residues 50-56 of SEQ ID NO:149 (CDR-L2); residues 50-56 of SEQ ID NO:151 (CDR-L2); residues 50-56 of SEQ ID NO:156 (CDR-L2); residues 50-56 of SEQ ID NO:167 (CDR-L2); residues 50-56 of SEQ ID NO:169 (CDR-L2); residues 50-56 of SEQ ID NO:171 (CDR-L2); residues 50-56 of SEQ ID NO:175 (CDR-L2); residues 50-56 of SEQ ID NO:176 (CDR-L2); residues 50-56 of SEQ ID NO:178 (CDR-L2); residues 50-56 of SEQ ID NO:180 (CDR-L2); residues 50-56 of SEQ ID NO:181 (CDR-L2); residues 50-56 of SEQ ID NO:185 (CDR-L2); and residues 50-56 of SEQ ID NO:187 (CDR-L2); or wherein the CDR-L3 is an amino acid selected from the group consisting of residues 89-97 of SEQ ID NO:59 (CDR-L3); residues 89-97 of SEQ ID NO:149 (CDR-L3); residues 89-97 of SEQ ID NO:150 (CDR-L3); residues 89-97 of SEQ ID NO:151 (CDR-L3); residues 89-97 of SEQ ID NO:155 (CDR-L3); residues 89-97 of SEQ ID NO:160 (CDR-L3); residues 89-97 of SEQ ID NO:167 (CDR-L3); residues 89-97 of SEQ ID NO:176 (CDR-L3); residues 89-97 of SEQ ID NO:181 (CDR-L3); residues 89-97 of SEQ ID NO:182 (CDR-L3); residues 89-97 of SEQ ID NO:183 (CDR-L3); and residues 89-97 of SEQ ID NO:188 (CDR-L3). 8. The method according to claim 1, wherein at least three CDRs are from a set of CDRs selected from the group of CDR sets consisting of: TABLE-US-00022 CDR Set SEQ ID NO. 1 residues 31-35 of SEQ ID NO: 60 (CDR-H1); residues 50-66 of SEQ ID NO: 60 (CDR-H2); residues 99-108 of SEQ ID NO: 60 (CDR-H3); 2 residues 31-35 of SEQ ID NO: 61 (CDR-H1); residues 50-66 of SEQ ID NO: 61 (CDR-H2); residues 99-108 of SEQ ID NO: 61 (CDR-H3); 3 residues 31-35 of SEQ ID NO: 63 (CDR-H1); residues 50-66 of SEQ ID NO: 63 (CDR-H2); residues 99-108 of SEQ ID NO: 63 (CDR-H3); 4 residues 31-35 of SEQ ID NO: 64 (CDR-H1); residues 50-66 of SEQ ID NO: 64 (CDR-H2); residues 99-108 of SEQ ID NO: 64 (CDR-H3); 5 residues 31-35 of SEQ ID NO: 65 (CDR-H1); residues 50-66 of SEQ ID NO: 65 (CDR-H2); residues 99-108 of SEQ ID NO: 65 (CDR-H3); 6 residues 31-35 of SEQ ID NO: 71 (CDR-H1); residues 50-66 of SEQ ID NO: 71 (CDR-H2); residues 99-108 of SEQ ID NO: 71 (CDR-H3); 7 residues 31-35 of SEQ ID NO: 73 (CDR-H1); residues 50-66 of SEQ ID NO: 73 (CDR-H2); residues 99-108 of SEQ ID NO: 73 (CDR-H3); 8 residues 31-35 of SEQ ID NO: 78 (CDR-H1); residues 50-66 of SEQ ID NO: 78 (CDR-H2); residues 99-108 of SEQ ID NO: 78 (CDR-H3); 9 residues 31-35 of SEQ ID NO: 81 (CDR-H1); residues 50-66 of SEQ ID NO: 81 (CDR-H2); residues 99-108 of SEQ ID NO: 81 (CDR-H3); 10 residues 31-35 of SEQ ID NO: 87 (CDR-H1); residues 50-66 of SEQ ID NO: 87 (CDR-H2); residues 99-108 of SEQ ID NO: 87 (CDR-H3); 11 residues 31-35 of SEQ ID NO: 92 (CDR-H1); residues 50-66 of SEQ ID NO: 92 (CDR-H2); residues 99-108 of SEQ ID NO: 92 (CDR-H3); 12 residues 31-35 of SEQ ID NO: 93 (CDR-H1); residues 50-66 of SEQ ID NO: 93 (CDR-H2); residues 99-108 of SEQ ID NO: 93 (CDR-H3); 13 residues 31-35 of SEQ ID NO: 95 (CDR-H1); residues 50-66 of SEQ ID NO: 95 (CDR-H2); residues 99-108 of SEQ ID NO: 95 (CDR-H3); 14 residues 31-35 of SEQ ID NO: 104 (CDR-H1); residues 50-66 of SEQ ID NO: 104 (CDR-H2); residues 99-108 of SEQ ID NO: 104 (CDR-H3); 15 residues 31-35 of SEQ ID NO: 105 (CDR-H1); residues 50-66 of SEQ ID NO: 105 (CDR-H2); residues 99-108 of SEQ ID NO: 105 (CDR-H3); 16 residues 31-35 of SEQ ID NO: 113 (CDR-H1); residues 50-66 of SEQ ID NO: 113 (CDR-H2); residues 99-108 of SEQ ID NO: 113 (CDR-H3); 17 residues 31-35 of SEQ ID NO: 114 (CDR-H1); residues 50-66 of SEQ ID NO: 114 (CDR-H2); residues 99-108 of SEQ ID NO: 114 (CDR-H3); 18 residues 31-35 of SEQ ID NO: 115 (CDR-H1); residues 50-66 of SEQ ID NO: 115 (CDR-H2); residues 99-108 of SEQ ID NO: 115 (CDR-H3); 19 residues 31-35 of SEQ ID NO: 117 (CDR-H1); residues 50-66 of SEQ ID NO: 117 (CDR-H2); residues 99-108 of SEQ ID NO: 117 (CDR-H3); 20 residues 31-35 of SEQ ID NO: 121 (CDR-H1); residues 50-66 of SEQ ID NO: 121 (CDR-H2); residues 99-108 of SEQ ID NO: 121 (CDR-H3); 21 residues 31-35 of SEQ ID NO: 131 (CDR-H1); residues 50-66 of SEQ ID NO: 131 (CDR-H2); residues 99-108 of SEQ ID NO: 131 (CDR-H3); 22 residues 31-35 of SEQ ID NO: 133 (CDR-H1); residues 50-66 of SEQ ID NO: 133 (CDR-H2); residues 99-108 of SEQ ID NO: 133 (CDR-H3); 23 residues 31-35 of SEQ ID NO: 140 (CDR-H1); residues 50-66 of SEQ ID NO: 140 (CDR-H2); residues 99-108 of SEQ ID NO: 140 (CDR-H3); 24 residues 24-34 of SEQ ID NO: 149 (CDR-L1); residues 50-56 of SEQ ID NO: 149 (CDR-L2); residues 89-97 of SEQ ID NO: 149 (CDR-L3); 25 residues 24-34 of SEQ ID NO: 150 (CDR-L1); residues 50-56 of SEQ ID NO: 150 (CDR-L2); residues 89-97 of SEQ ID NO: 150 (CDR-L3); 26 residues 24-34 of SEQ ID NO: 151 (CDR-L1); residues 50-56 of SEQ ID NO: 151 (CDR-L2); residues 89-97 of SEQ ID NO: 151 (CDR-L3); 27 residues 24-34 of SEQ ID NO: 153 (CDR-L1); residues 50-56 of SEQ ID NO: 153 (CDR-L2); residues 89-97 of SEQ ID NO: 153 (CDR-L3); 28 residues 24-34 of SEQ ID NO: 155 (CDR-L1); residues 50-56 of SEQ ID NO: 155 (CDR-L2); residues 89-97 of SEQ ID NO: 155 (CDR-L3); 29 residues 24-34 of SEQ ID NO: 156 (CDR-L1); residues 50-56 of SEQ ID NO: 156 (CDR-L2); residues 89-97 of SEQ ID NO: 156 (CDR-L3); 30 residues 24-34 of SEQ ID NO: 157 (CDR-L1); residues 50-56 of SEQ ID NO: 157 (CDR-L2); residues 89-97 of SEQ ID NO: 157 (CDR-L3); 31 residues 24-34 of SEQ ID NO: 159 (CDR-L1); residues 50-56 of SEQ ID NO: 159 (CDR-L2); residues 89-97 of SEQ ID NO: 159 (CDR-L3); 32 residues 24-34 of SEQ ID NO: 160 (CDR-L1); residues 50-56 of SEQ ID NO: 160 (CDR-L2); residues 89-97 of SEQ ID NO: 160 (CDR-L3); 33 residues 24-34 of SEQ ID NO: 162 (CDR-L1); residues 50-56 of SEQ ID NO: 162 (CDR-L2); residues 89-97 of SEQ ID NO: 162 (CDR-L3); 34 residues 24-34 of SEQ ID NO: 164 (CDR-L1); residues 50-56 of SEQ ID NO: 164 (CDR-L2); residues 89-97 of SEQ ID NO: 164 (CDR-L3); 35 residues 24-34 of SEQ ID NO: 165 (CDR-L1); residues 50-56 of SEQ ID NO: 165 (CDR-L2); residues 89-97 of SEQ ID NO: 165 (CDR-L3); 36 residues 24-34 of SEQ ID NO: 166 (CDR-L1); residues 50-56 of SEQ ID NO: 166 (CDR-L2); residues 89-97 of SEQ ID NO: 166 (CDR-L3); 37 residues 24-34 of SEQ ID NO: 167 (CDR-L1); residues 50-56 of SEQ ID NO: 167 (CDR-L2); residues 89-97 of SEQ ID NO: 167 (CDR-L3); 38 residues 24-34 of SEQ ID NO: 169 (CDR-L1); residues 50-56 of SEQ ID NO: 169 (CDR-L2); residues 89-97 of SEQ ID NO: 169 (CDR-L3); 39 residues 24-34 of SEQ ID NO: 171 (CDR-L1); residues 50-56 of SEQ ID NO: 171 (CDR-L2); residues 89-97 of SEQ ID NO: 171 (CDR-L3); 40 residues 24-34 of SEQ ID NO: 172 (CDR-L1); residues 50-56 of SEQ ID NO: 172 (CDR-L2); residues 89-97 of SEQ ID NO: 172 (CDR-L3); 41 residues 24-34 of SEQ ID NO: 174 (CDR-L1); residues 50-56 of SEQ ID NO: 174 (CDR-L2); residues 89-97 of SEQ ID NO: 174 (CDR-L3); 42 residues 24-34 of SEQ ID NO: 175 (CDR-L1); residues 50-56 of SEQ ID NO: 175 (CDR-L2); residues 89-97 of SEQ ID NO: 175 (CDR-L3); 43 residues 24-34 of SEQ ID NO: 176 (CDR-L1); residues 50-56 of SEQ ID NO: 176 (CDR-L2); residues 89-97 of SEQ ID NO: 176 (CDR-L3); 44 residues 24-34 of SEQ ID NO: 177 (CDR-L1); residues 50-56 of SEQ ID NO: 177 (CDR-L2); residues 89-97 of SEQ ID NO: 177 (CDR-L3); 45 residues 24-34 of SEQ ID NO: 178 (CDR-L1); residues 50-56 of SEQ ID NO: 178 (CDR-L2); residues 89-97 of SEQ ID NO: 178 (CDR-L3); 46 residues 24-34 of SEQ ID NO: 179 (CDR-L1); residues 50-56 of SEQ ID NO: 179 (CDR-L2); residues 89-97 of SEQ ID NO: 179 (CDR-L3); 47 residues 24-34 of SEQ ID NO: 180 (CDR-L1); residues 50-56 of SEQ ID NO: 180 (CDR-L2); residues 89-97 of SEQ ID NO: 180 (CDR-L3); 48 residues 24-34 of SEQ ID NO: 181 (CDR-L1); residues 50-56 of SEQ ID NO: 181 (CDR-L2); residues 89-97 of SEQ ID NO: 181 (CDR-L3); 49 residues 24-34 of SEQ ID NO: 182 (CDR-L1); residues 50-56 of SEQ ID NO: 182 (CDR-L2); residues 89-97 of SEQ ID NO: 182 (CDR-L3); 50 residues 24-34 of SEQ ID NO: 183 (CDR-L1); residues 50-56 of SEQ ID NO: 183 (CDR-L2); residues 89-97 of SEQ ID NO: 183 (CDR-L3); 51 residues 24-34 of SEQ ID NO: 184 (CDR-L1); residues 50-56 of SEQ ID NO: 184 (CDR-L2); residues 89-97 of SEQ ID NO: 184 (CDR-L3); 52 residues 24-34 of SEQ ID NO: 185 (CDR-L1); residues 50-56 of SEQ ID NO: 185 (CDR-L2); residues 89-97 of SEQ ID NO: 185 (CDR-L3); 53 residues 24-34 of SEQ ID NO: 187 (CDR-L1); residues 50-56 of SEQ ID NO: 187 (CDR-L2); residues 89-97 of SEQ ID NO: 187 (CDR-L3); 54 residues 24-34 of SEQ ID NO: 188 (CDR-L1); residues 50-56 of SEQ ID NO: 188 (CDR-L2); residues 89-97 of SEQ ID NO: 188 (CDR-L3); 55 residues 24-34 of SEQ ID NO: 189 (CDR-L1); residues 50-56 of SEQ ID NO: 189 (CDR-L2); residues 89-97 of SEQ ID NO: 189 (CDR-L3). 56 residues 24-34 of SEQ ID NO: 59 (CDR-L1); residues 50-56 of SEQ ID NO: 59 (CDR-L2); residues 89-97 of SEQ ID NO: 59 (CDR-L3). 9. The method according to claim 8, comprising CDRs from two CDR sets, wherein said two CDR sets comprise a VH CDR Set selected from the group consisting of CDR Sets 1-23, and a VL CDR Set selected from the group consisting of CDR Sets 24-56. 10. The method according to claim 9, further comprising a human acceptor framework. 11. The method according to claim 10, wherein said human acceptor framework comprises an amino acid sequence selected from the group consisting of SEQ ID NOS: 7-10, 13-16, 25, 240-316, and 317-381. 12. The method according to claim 10, wherein said human acceptor framework comprises at least one framework region amino acid substitution, wherein the amino acid sequence of the framework is at least 65% identical to the sequence of said human acceptor framework and comprises at least 70 amino acid residues identical to said human acceptor framework. 13. The method according to claim 10, 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 IL-1.beta.; a residue capable of interacting with a CDR; 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. 14. The method according to claim 13, wherein the key residue by Kabat numbering 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. 15. The method according to claim 10, wherein the binding protein comprises a consensus human variable domain. 16. The method 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 59-122 and 124-211. 17. The method according to claim 16, wherein said binding protein comprises two variable domains. 18. The method according to claim 17, wherein said two variable domains comprise amino acid sequences selected from the group consisting of: TABLE-US-00023 SEQ ID NO: 60 and SEQ ID NO: 149 SEQ ID NO: 198 and SEQ ID NO: 199 SEQ ID NO: 69 and SEQ ID NO: 173 SEQ ID NO: 202 and SEQ ID NO: 203 SEQ ID NO: 67 and SEQ ID NO: 151 SEQ ID NO: 206 and SEQ ID NO: 207 SEQ ID NO: 88 and SEQ ID NO: 159 SEQ ID NO: 210 and SEQ ID NO: 211 SEQ ID NO: 96 and SEQ ID NO: 155 SEQ ID NO: 103 and SEQ ID NO: 59 SEQ ID NO: 90 and SEQ ID NO: 182 SEQ ID NO: 104 and SEQ ID NO: 59 SEQ ID NO: 90 and SEQ ID NO: 167 SEQ ID NO: 105 and SEQ ID NO: 59 SEQ ID NO: 90 and SEQ ID NO: 164 SEQ ID NO: 106 and SEQ ID NO: 59 SEQ ID NO: 73 and SEQ ID NO: 174 SEQ ID NO: 107 and SEQ ID NO: 59 SEQ ID NO: 86 and SEQ ID NO: 159 SEQ ID NO: 108 and SEQ ID NO: 59 SEQ ID NO: 90 and SEQ ID NO: 169 SEQ ID NO: 109 and SEQ ID NO: 59 SEQ ID NO: 91 and SEQ ID NO: 165 SEQ ID NO: 110 and SEQ ID NO: 59 SEQ ID NO: 76 and SEQ ID NO: 175 SEQ ID NO: 111 and SEQ ID NO: 59 SEQ ID NO: 99 and SEQ ID NO: 189 SEQ ID NO: 112 and SEQ ID NO: 59 SEQ ID NO: 100 and SEQ ID NO: 168 SEQ ID NO: 113 and SEQ ID NO: 59 SEQ ID NO: 71 and SEQ ID NO: 170 SEQ ID NO: 114 and SEQ ID NO: 59 SEQ ID NO: 84 and SEQ ID NO: 188 SEQ ID NO: 115 and SEQ ID NO: 59 SEQ ID NO: 78 and SEQ ID NO: 179 SEQ ID NO: 116 and SEQ ID NO: 59 SEQ ID NO: 93 and SEQ ID NO: 176 SEQ ID NO: 117 and SEQ ID NO: 59 SEQ ID NO: 87 and SEQ ID NO: 154 SEQ ID NO: 118 and SEQ ID NO: 59 SEQ ID NO: 85 and SEQ ID NO: 162 SEQ ID NO: 119 and SEQ ID NO: 59 SEQ ID NO: 89 and SEQ ID NO: 170 SEQ ID NO: 120 and SEQ ID NO: 59 SEQ ID NO: 75 and SEQ ID NO: 181 SEQ ID NO: 121 and SEQ ID NO: 59 SEQ ID NO: 92 and SEQ ID NO: 184 SEQ ID NO: 122 and SEQ ID NO: 59 SEQ ID NO: 200 and SEQ ID NO: 201 SEQ ID NO: 204 and SEQ ID NO: 205 SEQ ID NO: 124 and SEQ ID NO: 59 SEQ ID NO: 208 and SEQ ID NO: 209 SEQ ID NO: 125 and SEQ ID NO: 59 SEQ ID NO: 63 and SEQ ID NO: 150 SEQ ID NO: 126 and SEQ ID NO: 59 SEQ ID NO: 97 and SEQ ID NO: 187 SEQ ID NO: 127 and SEQ ID NO: 59 SEQ ID NO: 90 and SEQ ID NO: 156 SEQ ID NO: 128 and SEQ ID NO: 59 SEQ ID NO: 92 and SEQ ID NO: 153 SEQ ID NO: 129 and SEQ ID NO: 59 SEQ ID NO: 94 and SEQ ID NO: 166 SEQ ID NO: 130 and SEQ ID NO: 59 SEQ ID NO: 82 and SEQ ID NO: 159 SEQ ID NO: 131 and SEQ ID NO: 59 SEQ ID NO: 101 and SEQ ID NO: 158 SEQ ID NO: 132 and SEQ ID NO: 59 SEQ ID NO: 96 and SEQ ID NO: 157 SEQ ID NO: 133 and SEQ ID NO: 59 SEQ ID NO: 70 and SEQ ID NO: 161 SEQ ID NO: 134 and SEQ ID NO: 59 SEQ ID NO: 83 and SEQ ID NO: 158 SEQ ID NO: 135 and SEQ ID NO: 59 SEQ ID NO: 102 and SEQ ID NO: 185 SEQ ID NO: 136 and SEQ ID NO: 59 SEQ ID NO: 98 and SEQ ID NO: 160 SEQ ID NO: 137 and SEQ ID NO: 59 SEQ ID NO: 74 and SEQ ID NO: 186 SEQ ID NO: 138 and SEQ ID NO: 59 SEQ ID NO: 95 and SEQ ID NO: 157 SEQ ID NO: 139 and SEQ ID NO: 59 SEQ ID NO: 72 and SEQ ID NO: 178 SEQ ID NO: 140 and SEQ ID NO: 59 SEQ ID NO: 96 and SEQ ID NO: 163 SEQ ID NO: 141 and SEQ ID NO: 59 SEQ ID NO: 77 and SEQ ID NO: 183 SEQ ID NO: 142 and SEQ ID NO: 59 SEQ ID NO: 90 and SEQ ID NO: 171 SEQ ID NO: 143 and SEQ ID NO: 59 SEQ ID NO: 79 and SEQ ID NO: 180 SEQ ID NO: 144 and SEQ ID NO: 59 SEQ ID NO: 381 and SEQ ID NO: 152 SEQ ID NO: 145 and SEQ ID NO: 59 SEQ ID NO: 81 and SEQ ID NO: 177 SEQ ID NO: 146 and SEQ ID NO: 59 SEQ ID NO: 80 and SEQ ID NO: 172 SEQ ID NO: 147 and SEQ ID NO: 59 SEQ ID NO: 196 and SEQ ID NO: 197 SEQ ID NO: 148 and SEQ ID NO: 59. 19. The method according to claim 9, wherein said two CDR sets comprise CDR Set 5 and CDR Set 56. 20. The method according to claim 16, wherein said at least one variable domain comprises the amino acid sequences of SEQ ID NO:204 and SEQ ID NO:205.

Details for Patent 9,409,986

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
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