IL-1 binding proteins

Patent metadata

Field	Value
Publication number	US-9409986-B2
Application number	US-201314133380-A
Country	US
Kind code	B2
Filing date	Dec 18, 2013
Priority date	May 14, 2010
Publication date	Aug 9, 2016
Grant date	Aug 9, 2016

Abstract

Proteins that bind IL-1α and IL-1β are described along with their use in compositions and methods for treating, preventing, and diagnosing IL-1-related disorders and for detecting IL-1α and IL-1β in cells, tissues, samples, and compositions.

First claim

What is claimed is:

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-1β, 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 1 -Y-D-M-S (SEQ ID NO:190), wherein;
X 1 is, K or R;

CDR-H2: Y-X 2 -S-X 4 -G-G-X 7 -G-T-Y-Y-P-D-X 14 -X 15 -K-G (SEQ ID NO:191), wherein;
X 2 is I or V;
X 4 is S or H;
X 7 is G or A;
X 14 is T or S; and
X 15 is V or A;

CDR-H3: G-G-V-X 4 -K-G-X 7 -F-D-X 10 (SEQ ID NO:192), wherein;
X 4 is T or Y;
X 7 is Y or C; and
X 10 is V, E, L, M, Q, or Y;

CDR-L1: R-A-S-G-N-I-X 7 -X 8 -X 9 -L-X 11 (SEQ ID NO:193), wherein;
X 7 is H, Y, or W;
X 8 is N, G, T, Q, E, H, D, or K;
X 9 is Y or W; and
X 11 is T, A, or N;

CDR-L2: X 1 -A-K-X 4 -L-X 6 -X 7 (SEQ ID NO:194), wherein;
X 1 is N, Q, or D;
X 4 is T, N, I, E, or S;
X 6 is A, M, or E; and
X 7 is D, E, S, or A;

and
CDR-L3: Q-X 2 -F-W-X 5 -X 6 -P-X 8 -X 9 (SEQ ID NO:195), wherein;
X 2 is H or Q;
X 5 is S, N, T, K, R, or M;
X 6 is I or L;
X 8 is Y or A; and
X 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™; an IgE inhibitor; an anti-IgE antibody; XOLAIR™; 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®; 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-1β 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-1β converting enzyme inhibitor; a TNF-α 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-β.

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-1β converting enzyme inhibitor; a TNF-α 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:1

Assignees

• Abbvie Inc
• Abbvie Inc

Inventors

• Wu Chengbin
• Ambrosi Dominic J
• Hsieh Chung-Ming
• Ghayur Tariq

Classifications

• A61P9/14

  Vasoprotectives; Antihaemorrhoidals; Drugs for varicose therapy; Capillary stabilisers · CPC title

• A61P3/10

  for hyperglycaemia, e.g. antidiabetics · CPC title

• A61P7/08

  Plasma substitutes; Perfusion solutions; Dialytics or haemodialytics; Drugs for electrolytic or acid-base disorders, e.g. hypovolemic shock (artificial tears A61P27/04) · CPC title

• A61P9/06

  Antiarrhythmics · CPC title

• A61P9/12

  Antihypertensives · CPC title