Method for treating an autoimmune disease using a soluble ctla4 molecule and a dmard or nsaid
AssigneeBristol-Myers Squibb Company
InventorsROBERT COHEN, SUZETTE CARR, DAVID HAGERTY, ROBERT JAMES PEACH, JEAN-CLAUDE BECKER
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Abstract
The present invention relates to compositions and methods for treating immune system diseases such as rheumatic disease, by administering to a subject soluble CTLA4 molecules that block endogenous B7 molecules from binding their ligands, alone, or in conjunction with other agents including Disease Modifying Anti-Rheumatic Drugs (DMARDs).
Claims38
A pharmaceutical composition comprising a pharmaceutically acceptable carrier and an effective amount of a first agent and a second agent, wherein
- a) the first agent is CTLA4Ig beginning with methionine at position +1 or with alanine at position −1 and ending with lysine at position +357 as shown in FIG. 24 (SEQ ID NO:
- 19), and
- b) the second agent is selected from a group consisting of immunosuppressive agents, corticosteroids, nonsteroidal
- anti-inflammatory drugs, prednisone, azathioprine, methotrexate, TNF (blockers or antagonists, infliximab, any biological agent targeting an inflammatory cytokine, hydroxychloroquine, sulphasalazopryine, gold salts, etanercept, anakinra, cyclophosphamide, leflunomide, collagen, dnaJ, a molecule that blocks TNF receptors, pegsunercept, a molecule that blocks cytokine function, AMG719, a molecule that blocks LFA-1 function, efalizumab, acetyl salicylic acid, choline magnesium salicylate, diflunisal, magnesium salicylate, salsalate, sodium salicylate, diclofenac, etodolac, fenoprofen, flurbiprofen, indomethacin, ketoprofen, ketorolac, meclofenamate, naproxen, nabumetone, phenylbutazone, piroxicam, sulindac, tolmetin, acetaminophen, ibuprofen, Cox-2 inhibitors, meloxicam, codeine phosphate, propoxyphene napsylate, oxycodone hydrochloride, oxycodone bitartrate and tramadol.
A kit for treating rheumatoid arthritis in a subject in need thereof comprising an effective amount of a first agent and a label and/or instructions, wherein
- a) the first agent is CTLA4Ig beginning with methionine at position +1 or with alanine at position −1 and ending with lysine at position +357 as shown in FIG. 24 (SEQ ID NO:
- 19);
- and
- b) the label and/or instructions indicate that an effective amount of the first agent is administered to a subject having active rheumatoid arthritis with an inadequate response to methotrexate.
A method for treating rheumatoid arthritis in a subject having active rheumatoid arthritis with an inadequate response to a TNF blocking agent comprising administering to the subject an effective amount of CTLA4Ig beginning with methionine at position +1 or with alanine at position −1 and ending with lysine at position +357 as shown in FIG. 24 (SEQ ID NO:
- 19).
A method for treating rheumatoid arthritis in a subject having active rheumatoid arthritis with an inadequate response to a TNF blocking agent, etanercept or infliximab comprising administering to the subject an effective amount of CTLA4Ig beginning with methionine at position +1 or with alanine at position −1 and ending with lysine at position +357 as shown in FIG. 24 (SEQ ID NO:
- 19);
- wherein the effective amount of the CTLA4Ig is 500 mg for a subject weighing less than 60 kg, 750 mg for a subject weighing between 60-100 kg or 1000 mg for a subject weighing more than 100 kg;
- wherein the effective amount of the CTLA4Ig molecule is administered at 2 and 4 weeks after the first infusion, then once a month thereafter;
- and wherein the effective amount of the CTLA4Ig is infused intravenously over 30 minutes.
A method for treating rheumatoid arthritis in a subject having active rheumatoid arthritis with an inadequate response to methotrexate comprising administering to the subject an effective amount of CTLA4Ig beginning with methionine at position +1 or with alanine at position −1 and ending with lysine at position +357 as shown in FIG. 24 (SEQ ID NO:
- 19).
A method for improving physical function in a subject having a rheumatic disease comprising administering an effective amount of a soluble CTLA4 fusion molecule comprising an extracellular domain of a CTLA4 molecule, wherein the extracellular domain of the CTLA4 molecule comprises the amino acids shown in SEQ ID NO:
- 17 beginning with methionine at position +27 or with alanine at position +26 and ending with aspartic acid at position +150.
A method for inducing a major clinical response in a subject having a rheumatic disease comprising administering an effective amount of a soluble CTLA4 fusion molecule comprising an extracellular domain of a CTLA4 molecule, wherein the extracellular domain of the CTLA4 molecule comprises the amino acids shown in SEQ ID NO:
- 17 beginning with methionine at position +27 or with alanine at position +26 and ending with aspartic acid at position +150.
Dependencies are inferred from the claim text.