Methods of treating systemic lupus erythematosus using a domain antibody directed against cd28

Abstract

Methods of treating autoimmune diseases, such as systemic lupus erythematosus using domain antibodies that specifically bind human CD28 are provided. The methods may comprise at least one administration cycle comprising one dose of the domain antibody. The method reduces symptoms of systemic lupus erythematosus compared to placebo.

1 . A method of treating an immune disease in a patient, comprising administering to the patient a therapeutically effective amount of an anti-CD28 domain antibody which comprises a variable domain, wherein the variable domain comprises the amino acid sequence of SEQ ID NO: 12 (1h-239-891(D70C)) or differs from SEQ ID NO: 12 by up to 5 amino acids, wherein at least one dose of the anti-CD28 domain antibody is administered at a dose from about 1.25 mg to about 12.5 mg. 
     
     
         2 . The method of  claim 1 , wherein the variable domain of the anti-CD28 domain antibody comprises: (1) a CDR1 region having the amino acid sequence of SEQ ID NO: 1; (2) a CDR2 region having the amino acid sequence of SEQ ID NO: 2; and (3) a CDR3 region having the amino acid sequence of SEQ ID NO: 3. 
     
     
         3 . The method of  claim 1 , wherein the anti-CD28 domain antibody comprises the amino acid sequence of SEQ ID NO: 12. 
     
     
         4 . The method of  claim 1 , wherein the anti-CD28 domain antibody comprises a 40 kDa branched polyethylene glycol. 
     
     
         5 . The method of  claim 1 , wherein the anti-CD28 domain antibody is BMS-931699. 
     
     
         6 . The method of  claim 1 , wherein the immune disease is systemic lupus erythematosus (SLE). 
     
     
         7 . The method of  claim 1 , wherein the dose is selected from about 1.25 mg, about 5 mg, and about 12.5 mg. 
     
     
         8 . The method of  claim 1 , wherein the dose is at least 1.25 mg. 
     
     
         9 . The method of  claim 1 , wherein the dose is at least 5 mg. 
     
     
         10 . The method of  claim 7 , wherein the dose is about 12.5 mg. 
     
     
         11 . The method of  claim 1 , wherein the dose is administered every week. 
     
     
         12 . The method of  claim 1 , wherein the dose is administered every two weeks. 
     
     
         13 . The method of  claim 1 , wherein at least 2 doses are administered. 
     
     
         14 . The method of  claim 13 , wherein the at least 2 doses are the same or different. 
     
     
         15 . The method of  claims 13 , wherein at least 12 doses are administered. 
     
     
         16 . The method of  claims 13 , wherein at least 24 doses are administered. 
     
     
         17 . The method of  claim 1 , wherein the anti-CD28 domain antibody is administered subcutaneously. 
     
     
         18 . The method of  claim 1 , further comprises administering to the patient an immunosuppressive/immunomodulatory and/or anti-inflammatory agent. 
     
     
         19 . The method of  claim 18 , wherein the immunosuppressive/immunomodulatory and/or anti-inflammatory agent is administered before or after the anti-CD28 domain antibody. 
     
     
         20 . The method of  claims 18 , wherein the immunosuppressive/immunomodulatory and/or anti-inflammatory agent is administered concurrently with the anti-CD28 domain antibody.