CA2261630C - Anti-tnf antibodies and methotrexate in the treatment of autoimmune disease - Google Patents

Anti-tnf antibodies and methotrexate in the treatment of autoimmune disease Download PDF

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Publication number
CA2261630C
CA2261630C CA2261630A CA2261630A CA2261630C CA 2261630 C CA2261630 C CA 2261630C CA 2261630 A CA2261630 A CA 2261630A CA 2261630 A CA2261630 A CA 2261630A CA 2261630 C CA2261630 C CA 2261630C
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alpha
necrosis factor
tumor necrosis
human tumor
antibody
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CA2261630A1 (en
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Marc Feldmann
Ravinder Nath Maini
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KENNEDY TRUST FOR RHEUMATOLOGY RESEARCH
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Kennedy Institute of Rheumotology
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Priority to CA2791778A priority Critical patent/CA2791778A1/en
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/177—Receptors; Cell surface antigens; Cell surface determinants
    • A61K38/1793—Receptors; Cell surface antigens; Cell surface determinants for cytokines; for lymphokines; for interferons
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
    • A61K39/39533—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals
    • A61K39/39541—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals against normal tissues, cells
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
    • A61K39/39533—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals
    • A61K39/3955—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals against proteinaceous materials, e.g. enzymes, hormones, lymphokines
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/24—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against cytokines, lymphokines or interferons
    • C07K16/241—Tumor Necrosis Factors
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/545—Medicinal preparations containing antigens or antibodies characterised by the dose, timing or administration schedule
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
    • C07K2317/24—Immunoglobulins specific features characterized by taxonomic origin containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
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  • Animal Behavior & Ethology (AREA)
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  • Immunology (AREA)
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  • Microbiology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Biomedical Technology (AREA)
  • Biophysics (AREA)
  • Molecular Biology (AREA)
  • Genetics & Genomics (AREA)
  • Rheumatology (AREA)
  • Endocrinology (AREA)
  • Cell Biology (AREA)
  • Zoology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Biochemistry (AREA)
  • Transplantation (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Pain & Pain Management (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Peptides Or Proteins (AREA)
  • Pyrane Compounds (AREA)
  • Steroid Compounds (AREA)

Abstract

Methods for treating and/or preventing a TNF-mediated disease in an individual are disclosed. Also disclosed is a composition comprising methotrexate and an anti-tumor necrosis factor antibody. TNF-mediated diseases include rheumatoid arthritis, Crohn's disease, and acute and chronic immune diseases associated with transplantation.

Description

ANTI-TNF ANTIBODIES AND METHOTREXATE

Claims (42)

CLAIMS:
1. Use of an anti-human tumor necrosis factor-.alpha. monoclonal antibody or a human tumor necrosis factor-.alpha. binding Fab fragment thereof for the manufacture of a medicament for performing adjunctive therapy with a medicament comprising methotrexate on an individual suffering from rheumatoid arthritis whose active disease is incompletely controlled despite already receiving methotrexate, to reduce or eliminate signs and symptoms associated with the rheumatoid arthritis, wherein the anti-human tumor necrosis factor-.alpha.
antibody or human tumor necrosis factor-a binding Fab fragment (a) binds to an epitope on human tumor necrosis factor-.alpha., and (b) inhibits binding of human tumor necrosis factor-.alpha. to human tumor necrosis factor-.alpha. cell surface receptors.
2. Use of an anti-human tumor necrosis factor-.alpha. monoclonal antibody or a human tumor necrosis factor-.alpha. binding Fab fragment thereof for the manufacture of a medicament for performing adjunctive therapy with a medicament comprising methotrexate on an individual suffering from rheumatoid arthritis who still has active disease despite prior therapy with methotrexate and who is already being treated with methotrexate, to reduce or eliminate signs and symptoms associated with the rheumatoid arthritis, wherein the anti-human tumor necrosis factor-.alpha. antibody or human tumor necrosis factor-.alpha. binding Fab fragment inhibits binding of human tumor necrosis factor-.alpha. to human tumor necrosis factor-a cell surface receptors.
3. The use of claim 1 or 2, wherein the anti-tumor necrosis factor-.alpha. antibody is a chimeric antibody.
4. The use of claim 3, wherein the chimeric antibody binds to the epitope of human tumor necrosis factor-.alpha. recognized by a cA2 antibody.
5. The use of any one of claims 1 to 4, wherein the antibody is infliximab.
6. The use of any one of claims 1 to 5, wherein the anti-human tumor necrosis factor-.alpha. antibody-containing medicament is formulated for administration via infusion.
7. The use of any one of claims 1 to 6, wherein the anti-human tumor necrosis factor-.alpha. antibody or a human tumor necrosis factor-.alpha. binding Fab fragment-containing medicament is formulated for administration at an interval of one day to thirty weeks.
8. The use according to any one of claims 1 to 7, wherein the methotrexate-containing medicament is formulated for administration in the form of a series of low doses separated by intervals of days or weeks.
9. The use according to any one of claims 1 to 8, wherein the anti-human tumor necrosis factor-a antibody or human tumor necrosis factor-.alpha. binding Fab fragment-containing medicament is formulated for administration multiple times, spaced at an interval of weeks.
10. The use of any one of claims 1 to 9, wherein (a) the anti-human tumor necrosis factor-.alpha. antibody or human tumor necrosis factor-.alpha. binding Fab fragment-containing medicament is formulated for administration multiple times, spaced at an interval of weeks, and (b) the methotrexate-containing medicament is formulated for administration at intervals of weeks.
11. The use of any one of claims 1 to 10, wherein the methotrexate-containing medicament contains 10 milligrams of methotrexate.
12. The use of any one of claims 1 to 10, wherein (a) the methotrexate-containing medicament contains 7.5mg of methotrexate and is formulated for administration weekly beginning at week 0, and (b) the anti-TNF.alpha. antibody is infliximab and the anti-human tumor necrosis factor-.alpha.
antibody or human tumor necrosis factor-.alpha. binding Fab fragment-containing medicament is formulated for administration by infusion at weeks 0, 2, 6, 10 and 14.
13. The use according to any one of claims 1 to 12, wherein the anti-tumor necrosis factor .alpha. antibody is a chimeric monoclonal antibody, and the anti-human tumor necrosis factor-.alpha. antibody or human tumor necrosis factor-.alpha. binding Fab fragment-containing medicament is formulated for administration as multiple infusions.
14. The use according to any one of claims 1 to 11, wherein (a) the anti- tumor necrosis factor a antibody is infliximab, (b) the anti-human tumor necrosis factor-.alpha. antibody or human tumor necrosis factor-.alpha. binding Fab fragment-containing medicament is formulated for administration in combination with the methotrexate-containing medicament as a single infusion of anti-TNF antibody, and (c) the methotrexate-containing medicament contains 10 milligrams of methotrexate.
15. The use according to any one of claims 1 to 11, wherein (a) the anti- tumor necrosis factor a antibody is infliximab, (b) the anti-human tumor necrosis factor-.alpha.
antibody or human tumor necrosis factor-.alpha. binding Fab fragment-containing medicament is formulated for administration as a repeated infusion, and (c) the methotrexate-containing medicament contains 10 milligrams of methotrexate.
16. The use according to any one of claims 1 to 15, wherein the anti-human tumor necrosis factor-.alpha. antibody or human tumor necrosis factor-.alpha. binding Fab fragment is infliximab.
17. A pharmaceutical composition comprising an anti-human tumor necrosis factor-.alpha. monoclonal antibody or a human tumor necrosis factor-.alpha. binding Fab fragment thereof, in admixture with a pharmaceutically acceptable diluent or carrier, for use in performing adjunctive therapy with a medicament comprising methotrexate on an individual suffering from rheumatoid arthritis whose active disease is incompletely controlled despite already receiving methotrexate, to reduce or eliminate signs and symptoms associated with the rheumatoid arthritis, wherein the anti-human tumor necrosis factor-.alpha. antibody or human tumor necrosis factor-.alpha. binding Fab fragment (a) binds to an epitope on human tumor necrosis factor-.alpha., and (b) inhibits binding of human tumor necrosis factor-.alpha. to human tumor necrosis factor-.alpha. cell surface receptors.
18. A pharmaceutical composition comprising an anti-human tumor necrosis factor-.alpha. monoclonal antibody or a human tumor necrosis factor-.alpha. binding Fab fragment thereof, in admixture with a pharmaceutically acceptable diluent or carrier, for use in performing adjunctive therapy with a medicament comprising methotrexate on an individual suffering from rheumatoid arthritis who still has active disease despite prior therapy with methotrexate and who is already being treated with methotrexate, to reduce or eliminate signs and symptoms associated with the rheumatoid arthritis, wherein the anti-human tumor necrosis factor-.alpha. antibody or human tumor necrosis factor-.alpha. binding Fab fragment inhibits binding of human tumor necrosis factor-.alpha. to human tumor necrosis factor-.alpha. cell surface receptors.
19. The pharmaceutical composition of claim 16 or 17, wherein the anti-tumor necrosis factor-.alpha. antibody is a chimeric antibody.
20. The pharmaceutical composition of claim 19, wherein the chimeric antibody binds to the epitope of human tumor necrosis factor-.alpha. recognized by a cA2 antibody.
21. The pharmaceutical composition of any one of claims 17 to 20, wherein the antibody is infliximab.
22. The pharmaceutical composition of any one of claims 17 to 21, wherein the anti-human tumor necrosis factor-.alpha.
antibody or human tumor necrosis factor-.alpha. binding Fab fragment-containing medicament is formulated for administration via infusion.
23. The pharmaceutical composition of any one of claims 17 to 22, wherein the anti-human tumor necrosis factor-.alpha.
antibody or human tumor necrosis factor-.alpha. binding Fab fragment-containing medicament is formulated for administration at an interval of one day to thirty weeks.
24. The pharmaceutical composition of any one of claims 17 to 23, wherein the methotrexate-containing medicament is formulated for administration in the form of a series of low doses separated by intervals of days or weeks.
25. The pharmaceutical composition of any one of claims 17 to 24, wherein the anti-human tumor necrosis factor-.alpha.
antibody or human tumor necrosis factor-.alpha. binding Fab fragment-containing medicament is formulated for administration multiple times, spaced at an interval of weeks.
26. The pharmaceutical composition of any one of claims 17 to 25, wherein (a) the anti-human tumor necrosis factor-.alpha.
antibody or human tumor necrosis factor-.alpha. binding Fab fragment-containing medicament is formulated for administration multiple times, spaced at an interval of weeks and (b) the methotrexate-containing medicament is formulated for administration at intervals of weeks.
27. The pharmaceutical composition of any one of claims 17 to 26, wherein the methotrexate-containing medicament contains 10 milligrams of methotrexate.
28. The pharmaceutical composition of any one of claims 17 to 26, wherein (a) the methotrexate-containing medicament contains 7.5 mg of methotrexate and is formulated for administration weekly beginning at week 0, and (b) the anti-human tumor necrosis factor-.alpha. antibody is infliximab and the anti-human tumor necrosis factor-.alpha. antibody or human tumor necrosis factor-.alpha. binding Fab fragment-containing medicament is formulated for administration by infusion at weeks 0, 2, 6, 10 and 14.
29. The pharmaceutical composition of any one of claims 17 to 28, wherein the anti- tumor necrosis factor .alpha. antibody is a chimeric monoclonal antibody, and the anti-human tumor necrosis factor-.alpha. antibody or human tumor necrosis factor-.alpha.
binding Fab fragment-containing medicament is formulated for administration as multiple infusions.
30. The pharmaceutical composition of any one of claims 17 to 27, wherein (a) the anti- tumor necrosis factor a antibody is infliximab, (b) the anti-human tumor necrosis factor-.alpha.
antibody or human tumor necrosis factor-.alpha. binding Fab fragment-containing medicament is formulated for administration in combination with the methotrexate-containing medicament as a single infusion, and (c) the methotrexate-containing medicament contains 10 milligrams of methotrexate.
31. The pharmaceutical composition of any one of claims 17 to 27, wherein (a) the anti- tumor necrosis factor .alpha. antibody is infliximab, (b) the anti-human tumor necrosis factor-.alpha.
antibody or human tumor necrosis factor-.alpha. binding Fab fragment-containing medicament is formulated for administration as a repeated infusion, and (c) the methotrexate-containing medicament contains 10 milligrams of methotrexate.
32. The pharmaceutical composition of any one of claims 17 to 28, wherein the anti-human tumor necrosis factor-.alpha.
antibody or human tumor necrosis factor-.alpha. binding Fab fragment-containing medicament is formulated for administration as a dosage form containing from about 0.1 milligram to about 500 milligrams of the anti anti-human tumor necrosis factor-.alpha. antibody or human tumor necrosis factor-.alpha. binding Fab fragment.
33. The pharmaceutical composition of any one of claims 17 to 28, wherein the anti-human tumor necrosis factor-.alpha.
antibody is infliximab and the anti-human tumor necrosis factor-.alpha. antibody or human tumor necrosis factor-.alpha. binding Fab fragment-containing medicament is formulated for administration as a dosage form containing from about 0.1 milligram to about 500 milligrams of infliximab.
34. The pharmaceutical composition of any one of claims 17 to 33, wherein the anti-human tumor necrosis factor-.alpha.
antibody or human tumor necrosis factor-.alpha. binding Fab fragment is infliximab.
35. The pharmaceutical composition of any one of claims 17 to 20, wherein the antibody is a humanized antibody.
36. The use of any one of claims 1 to 4, wherein the antibody is a humanized antibody.
37. The use of any one of claims 1 to 4, wherein the antibody is a recombinant antibody.
38. The pharmaceutical composition of any one of claims 17 to 20, wherein the antibody is a recombinant antibody.
39. Use of an anti-human tumor necrosis factor-.alpha. monoclonal antibody for the manufacture of a medicament for performing adjunctive therapy with methotrexate for the reduction in signs and symptoms, inhibition of the progression of structural damage, or improving physical function in an adult patient with moderately to severely active rheumatoid arthritis whose active disease is incompletely controlled despite already receiving methotrexate, wherein the anti-human tumor necrosis factor-.alpha. antibody (a) binds to an epitope on human tumor necrosis factor-.alpha., and (b) inhibits binding of human tumor necrosis factor-.alpha. to human tumor necrosis factor-.alpha. cell surface receptors.
40. Use of an anti-human tumor necrosis factor-.alpha. monoclonal antibody for the manufacture of a medicament for performing adjunctive therapy with methotrexate for the reduction in signs and symptoms, inhibition of the progression of structural damage, or improving physical function in an adult patient with moderately to severely active rheumatoid arthritis who still has active disease despite prior therapy with methotrexate and who is already being treated with methotrexate, wherein the anti-human tumor necrosis factor-.alpha.
antibody inhibits binding of human tumor necrosis factor-.alpha. to human tumor necrosis factor-.alpha. cell surface receptors.
41. A pharmaceutical composition comprising an anti-human tumor necrosis factor-.alpha. monoclonal antibody, in admixture with a pharmaceutically acceptable diluent or carrier, for use in performing adjunctive therapy with methotrexate for the reduction in signs and symptoms, inhibition of the progression of structural damage, or improving physical function in an adult patient with moderately to severely active rheumatoid arthritis whose active disease is incompletely controlled despite already receiving methotrexate, wherein the anti-human tumor necrosis factor-.alpha.
antibody (a) binds to an epitope on human tumor necrosis factor-.alpha., and (b) inhibits binding of human tumor necrosis factor-.alpha. to human tumor necrosis factor-.alpha. cell surface receptors.
42. A pharmaceutical composition comprising an anti-human tumor necrosis factor-.alpha. monoclonal antibody, in admixture with a pharmaceutically acceptable diluent or carrier, for use in performing adjunctive therapy with methotrexate for the reduction in signs and symptoms, inhibition of the progression of structural damage, or improving physical function in an adult patient with moderately to severely active rheumatoid arthritis who still has active disease despite prior therapy with methotrexate and who is already being treated with methotrexate, wherein the anti-human tumor necrosis factor-.alpha. antibody inhibits binding of human tumor necrosis factor-.alpha. to human tumor necrosis factor-.alpha. cell surface receptors.
CA2261630A 1996-08-01 1997-08-01 Anti-tnf antibodies and methotrexate in the treatment of autoimmune disease Expired - Lifetime CA2261630C (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CA2791778A CA2791778A1 (en) 1996-08-01 1997-08-01 Anti-tnf antibodies and methotrexate in the treatment of autoimmune disease

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US08/690,775 1996-08-01
US08/690,775 US6270766B1 (en) 1992-10-08 1996-08-01 Anti-TNF antibodies and methotrexate in the treatment of arthritis and crohn's disease
PCT/GB1997/002058 WO1998005357A1 (en) 1996-08-01 1997-08-01 Anti-tnf antibodies and methotrexate in the treatment of autoimmune disease

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CA2791778A Division CA2791778A1 (en) 1996-08-01 1997-08-01 Anti-tnf antibodies and methotrexate in the treatment of autoimmune disease

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CA2261630A1 CA2261630A1 (en) 1998-02-12
CA2261630C true CA2261630C (en) 2012-12-04

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CA2261630A Expired - Lifetime CA2261630C (en) 1996-08-01 1997-08-01 Anti-tnf antibodies and methotrexate in the treatment of autoimmune disease

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US (10) US6270766B1 (en)
EP (3) EP1593393B1 (en)
AT (2) ATE535255T1 (en)
AU (1) AU719015B2 (en)
CA (2) CA2791778A1 (en)
DE (1) DE69734317T2 (en)
DK (3) DK0914157T3 (en)
ES (3) ES2247635T3 (en)
LU (4) LU92004I2 (en)
PT (2) PT1593393E (en)
WO (1) WO1998005357A1 (en)

Cited By (1)

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Publication number Priority date Publication date Assignee Title
US9399061B2 (en) 2006-04-10 2016-07-26 Abbvie Biotechnology Ltd Methods for determining efficacy of TNF-α inhibitors for treatment of rheumatoid arthritis

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US20030225254A1 (en) * 1989-08-07 2003-12-04 Rathjen Deborah Ann Tumour necrosis factor binding ligands
US6277969B1 (en) * 1991-03-18 2001-08-21 New York University Anti-TNF antibodies and peptides of human tumor necrosis factor
US6764681B2 (en) * 1991-10-07 2004-07-20 Biogen, Inc. Method of prophylaxis or treatment of antigen presenting cell driven skin conditions using inhibitors of the CD2/LFA-3 interaction
US6270766B1 (en) 1992-10-08 2001-08-07 The Kennedy Institute Of Rheumatology Anti-TNF antibodies and methotrexate in the treatment of arthritis and crohn's disease
US6770279B1 (en) * 1992-10-08 2004-08-03 The Kennedy Institute Of Rheumatology TNFα antagonists and cyclosporin in therapy of rheumatoid arthritis
US7070783B1 (en) 1995-05-09 2006-07-04 The Mathilda And Terence Kennedy Institute Of Rheumatology Small molecular weight TNF receptor multimeric molecule
US6090382A (en) 1996-02-09 2000-07-18 Basf Aktiengesellschaft Human antibodies that bind human TNFα
ATE239041T1 (en) * 1996-02-09 2003-05-15 Basf Ag HUMAN ANTIBODIES THAT BIND TO HUMAN TNFALPHA
TW555765B (en) 1996-07-09 2003-10-01 Amgen Inc Low molecular weight soluble tumor necrosis factor type-I and type-II proteins
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