Methods of treating autoimmune disease using a domain antibody directed against cd40l

Abstract

Methods of treating autoimmune diseases, such as primary immune thrombocytopenia (ITP), solid organ transplant rejection, graft-related disease, pemphigus vulgaris, systemic sclerosis, and myasthenia gravis using antibody polypeptides that specifically bind human CD40L are provided. The antibody polypeptides do not activate platelets. The methods may comprise at least one administration cycle comprising one dose of the antibody polypeptide. The dose may be administered intravenously at a dose from about 75 mg to about 1500 mg. The method normalizes platelet counts in the human patient.

1 . A method of treating an immune disease in a patient, comprising administering to the patient a therapeutically effective amount of an antibody polypeptide which comprises: (1) a variable domain wherein the amino acid sequence of the variable domain comprises BMS2h-572-633 (SEQ ID NO: 5) or differs from SEQ ID NO: 5 by up to 5 amino acids; and (2) a human Fc domain, wherein at least one dose of the antibody polypeptide is administered at a dose of about 75 mg to about 1500 mg. 
     
     
         2 . The method of  claim 1 , wherein the variable domain of the antibody polypeptide comprises: (1) a CDR1 region having the amino acid sequence of SEQ ID NO: 2; (2) a CDR2 region having the amino acid sequence of SEQ ID NO: 3; and (1) a CDR3 region having the amino acid sequence of SEQ ID NO: 4. 
     
     
         3 . The method of  claim 1 , wherein the variable domain of the antibody polypeptide comprises an amino acid sequence that is at least 95% identical to SEQ ID NO: 5. 
     
     
         4 . The method of  claim 1 , wherein the antibody polypeptide comprises the amino acid sequence of SEQ ID NO: 6. 
     
     
         5 . The method of  claim 1 , wherein the antibody polypeptide is BMS-986004. 
     
     
         6 . The method of  claim 1 , wherein the immune disease is primary immune thrombocytopenia (ITP). 
     
     
         7 . The method of  claim 1 , wherein the dose is selected from about 75 mg, about 225 mg, about 675 mg, and about 1500 mg. 
     
     
         8 . The method of  claim 1 , wherein the dose is from about 200 mg to about 1200 mg. 
     
     
         9 . The method of  claim 1 , wherein the dose is administered once every 2 weeks. 
     
     
         10 . The method of  claim 1 , wherein the antibody polypeptide is formulated in a pharmaceutical composition for intravenous administration. 
     
     
         11 . The method of  claim 10 , wherein the pharmaceutical composition comprises a pharmaceutically acceptable carrier. 
     
     
         12 . The method of  claim 1 , wherein the antibody polypeptide is administered intravenously. 
     
     
         13 . The method of  claim 1 , wherein at least 2 doses are administered, and the at least 2 doses are different. 
     
     
         14 . The method of  claim 1 , wherein at least 2 doses are administered, and the at least 2 doses are the same. 
     
     
         15 . The method of  claim 1 , wherein at least 7 doses are administered. 
     
     
         16 . The method of  claim 1 , wherein the therapeutically effective amount of the antibody polypeptide normalizes platelet counts in the patient. 
     
     
         17 . The method of  claim 1 , wherein the patient has a peripheral blood platelet count that increases by at least 20,000/mm 3  after treatment. 
     
     
         18 . The method of  claim 1 , wherein the patient has a peripheral blood platelet count of less than 30,000/mm 3  before treatment. 
     
     
         19 . The method of  claim 1 , wherein the patient was splenectomized prior to treatment. 
     
     
         20 . The method of  claim 1 , wherein the method further comprises administering an immunosuppressive/immunomodulatory and/or anti-inflammatory agent to the human patient.