# US 7,611,702 B2 · TNF-alpha blocker treatment for enterocolitis associated with immunostimulatory therapeutic antibody therapy > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 7,611,702 B2 - Document ID: US7611702B2 - Status: Granted - Kind: B2 - Application number: 11/557,835 - Filed: 2006-11-08 - Published: 2007-10-25 - Granted: 2009-11-03 - Earliest claimed: 2005-11-08 - Assignees: Medarex, Inc. - Inventors: Steven Fischkoff; Israel Lowy; Michael Yellin; James Chung-Yin Yang - Web page: https://patentgrep.com/patent/US7611702B2 ## CPC - A61K 39/39558: {against tumor tissues, cells, antigens} - A61K 39/3955: {against proteinaceous materials, e.g. enzymes, hormones, lymphokines} - A61P 1/04: for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants - A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 - C07K 16/241: {Tumor Necrosis Factors} - C07K 16/2818: {against CD28 or CD152} - A61K 2039/507: {Comprising a combination of two or more separate antibodies} - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS - C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00) ## Abstract The present invention provides methods for treating adverse events related to immunotherapy. More specifically, the present invention provides methods for treating the enterocolitis associated with anti-CTLA-4 antibody immunotherapy. ## Claims ### Claim 1 A method for treating enterocolitis induced by an-anti-CTLA-4 antibody in a patient, comprising administering to the patient an amount of a TNF-α blocking agent effective to treat the enterocolitis, wherein the TNF-α blocking agent is selected from the group consisting of an anti-TNF-α antibody and a TNF receptor fusion protein. ### Claim 2 (depends on 1) The method of claim 1, wherein the anti-CTLA-4 antibody is a human sequence antibody that binds to human CTLA-4. ### Claim 3 (depends on 2) The method of claim 2, wherein the anti-CTLA-4 antibody is 10D1 (ipilimumab). ### Claim 4 (depends on 1) The method of claim 1, wherein the anti-TNF-α antibody is selected from the group consisting of infliximab, certolizumab pegol (CDP870), golimumab and adalimumab. ### Claim 5 (depends on 4) The method of claim 4, wherein the anti-TNF-α antibody is infliximab. ### Claim 6 (depends on 5) The method of claim 5, comprising administering infliximab in a single dose of about 5 mg/kg. ### Claim 7 (depends on 1) The method of claim 1, wherein the TNF-α blocking agent is administered intravenously. ### Claim 8 (depends on 1) The method of claim 1, wherein the anti-CTLA-4 antibody is for the treatment of cancer. ### Claim 9 (depends on 8) The method of claim 8, wherein the cancer is metastatic melanoma or renal cell carcinoma. ### Claim 10 A method for treating enterocolitis induced by an-anti-CTLA-4 antibody in a patient, comprising administering to the patient an amount of a TNF-α blocking agent effective to treat the enterocolitis, wherein the TNF-α blocking agent is selected from the group consisting of an anti-TNF-α antibody and a TNF receptor fusion protein, wherein the enterocolitis induced by an anti-CTLA-4 antibody is refractory to steroid treatment. ### Claim 11 (depends on 10) The method of claim 10, wherein the anti-CTLA-4 antibody is a human sequence antibody that binds to human CTLA-4. ### Claim 12 (depends on 11) The method of claim 11, wherein the anti-CTLA-4 antibody is 10D1 (ipilimumab). ### Claim 13 (depends on 10) The method of claim 10, wherein the anti-TNF-α antibody is selected from the group consisting of infliximab, certolizumab pegol (CDP870), golimunab, and adalimumab. ### Claim 14 (depends on 13) The method of claim 13, wherein the anti-TNF-α antibody is infliximab. ### Claim 15 (depends on 14) The method of claim 14, comprising administering infliximab in a single dose of about 5 mg/kg. ### Claim 16 (depends on 10) The method of claim 10, wherein the TNF-α blocking agent is administered intravenously. ### Claim 17 (depends on 10) The method of claim 10, wherein the anti-CTLA-4 antibody is for the treatment of cancer. ### Claim 18 (depends on 17) The method of claim 17, wherein the cancer is metastatic melanoma or renal cell carcinoma. ### Claim 19 (depends on 1, 10) The method of claim 1 or 10, further comprising administering an effective amount of a gut-decontaminating antibiotic to the patient. ### Claim 20 (depends on 1, 10) The method of claim 1 or 10, wherein the TNF receptor fusion protein is etanercept.