Therapeutic nuclease compositions and methods

Abstract

Hybrid nuclease molecules and methods for treating an immune-related disease or disorder in a mammal, and a pharmaceutical composition for treating an immune-related disease in a mammal.

1 . A hybrid nuclease molecule comprising a first nuclease domain and an Fc domain, wherein the first nuclease domain is operatively coupled to the Fc domain. 
     
     
         2 . The hybrid nuclease molecule of  claim 1 , wherein the hybrid nuclease molecule is a polypeptide, wherein the amino acid sequence of the first nuclease domain comprises a human, wild-type RNase amino acid sequence as set forth in SEQ ID NO:149, wherein the amino acid sequence of the Fc domain comprises a human, wild-type IgG1 Fc domain amino acid sequence as set forth in SEQ ID NO:145. 
     
     
         3 . The hybrid nuclease molecule of  claim 1 , wherein the hybrid nuclease molecule is a polypeptide consisting of SEQ ID NO:163. 
     
     
         4 . A pharmaceutical composition comprising at least one hybrid nuclease molecule and/or at least one dimeric polypeptide according  claim 1 , and a pharmaceutically acceptable excipient. 
     
     
         5 . A nucleic acid molecule encoding the hybrid nuclease molecule according to  claim 1 . 
     
     
         6 . A recombinant expression vector comprising a nucleic acid molecule according to  claim 5 . 
     
     
         7 . A host cell transformed with the recombinant expression vector according to  claim 6 . 
     
     
         8 . A method of making the hybrid nuclease molecule of  claim 1 , comprising: providing a host cell comprising a nucleic acid sequence that encodes the hybrid nuclease molecule; and maintaining the host cell under conditions in which the hybrid nuclease molecule is expressed. 
     
     
         9 . A method for treating or preventing a condition associated with an abnormal immune response, comprising administering to a patient in need thereof an effective amount of an isolated hybrid nuclease molecule of  claim 1 . 
     
     
         10 . The method of  claim 9 , wherein the condition is an autoimmune disease. 
     
     
         11 . The method of  claim 10 , wherein the autoimmune disease is selected from the group consisting of insulin-dependent diabetes mellitus, multiple sclerosis, experimental autoimmune encephalomyelitis, rheumatoid arthritis, experimental autoimmune arthritis, myasthenia gravis, thyroiditis, an experimental form of uveoretinitis, Hashimoto's thyroiditis, primary myxoedema, thyrotoxicosis, pernicious anaemia, autoimmune atrophic gastritis, Addison's disease, premature menopause, male infertility, juvenile diabetes, Goodpasture's syndrome, pemphigus vulgaris, pemphigoid, sympathetic ophthalmia, phacogenic uveitis, autoimmune haemolytic anaemia, idiopathic leucopenia, primary biliary cirrhosis, active chronic hepatitis Hbs-ve, cryptogenic cirrhosis, ulcerative colitis, Sjogren's syndrome, scleroderma, Wegener's granulomatosis, polymyositis, dermatomyositis, discoid LE, systemic lupus erythematosus (SLE), and connective tissue disease. 
     
     
         12 . The method of  claim 11 , wherein the autoimmune disease is SLE.