Selective il-6-trans-signalling inhibitor compositions

Abstract

A selective IL-6-trans-signalling inhibitor can be used to treat a variety of IL-6-mediated conditions, including inflammatory diseases and cancer. The inhibitor can safely be administered to humans at a variety of doses.

1 - 16 . (canceled) 
     
     
         17 . A polypeptide dimer comprising two gp130-Fc monomers having at least 90% sequence identity to SEQ ID NO: 1, wherein the polypeptide dimer comprises no greater than 6% of galactose-alpha-1,3-galactose per mole polypeptide. 
     
     
         18 . The polypeptide dimer of  claim 17 , wherein the polypeptide dimer comprises glycans, and wherein a mean of at least 52% of the glycans include one or more sialic acid residues. 
     
     
         19 . The polypeptide dimer of  claim 17  obtainable by expressing a polypeptide having at least 90% sequence identity to SEQ ID NO: 1 in cells, culturing the cells in culture media, and collecting said polypeptide dimers from said cells and/or cell culture media. 
     
     
         20 . The polypeptide dimer of  claim 17  obtainable by expressing a polypeptide having at least 90% sequence identity to SEQ ID NO: 1 in mammalian cells, performing multiple rounds of cell line selection, selecting a cell line producing said polypeptide dimer, culturing the cells in culture media, and collecting said polypeptide dimers from said cells and/or cell culture media. 
     
     
         21 . The polypeptide dimer of  claim 20 , wherein the mammalian cells are Chinese Hamster Ovary (CHO) cells. 
     
     
         22 . A composition comprising the polypeptide dimer of  claim 17 , wherein:
 a. no greater than 5% of the polypeptide dimer is present as an oligomeric aggregate,   b. the composition comprises no greater than 4.0% by weight of polypeptides that are a truncated variation of the polypeptide of SEQ ID NO: 1 with respect to polypeptides of SEQ ID NO: 1 or   c. both.   
     
     
         23 . A composition according to  claim 22 , wherein the composition further comprises a nonionic surfactant. 
     
     
         24 . A composition according to  claim 17 , wherein the composition further comprises a buffering agent and a sugar. 
     
     
         25 . A method for producing a polypeptide dimer according to  claim 17 , comprising expressing a polypeptide having at least 90% sequence identity to SEQ ID NO: 1 in cells, culturing the cells in culture media, and collecting said polypeptide dimers from said cells and/or cell culture media. 
     
     
         26 . The method of  claim 25 , wherein said cells are Chinese Hamster Ovary (CHO) cells. 
     
     
         27 . The method of  claim 25 , comprising expressing a polypeptide having at least 90% sequence identity to SEQ ID NO: 1 in cells, performing multiple rounds of cell line selection, selecting a cell line producing said polypeptide dimer, culturing the cells in culture media, and collecting said polypeptide dimers from said cells and/or cell culture media. 
     
     
         28 . The method of  claim 27 , wherein said cells are mammalian cells. 
     
     
         29 . The method of  claim 27 , wherein said cells are Chinese Hamster Ovary (CHO) cells. 
     
     
         30 . A method for treating an inflammatory disease or an IL-6-mediated condition in a human comprising administering to a human in need thereof the polypeptide dimers according to  claim 17 . 
     
     
         31 . The method according to  claim 30 , wherein the inflammatory disease or IL-6-mediated condition is inflammatory bowel disease. 
     
     
         32 . The method according to  claim 30 , wherein the inflammatory disease or IL-6-mediated condition is rheumatoid arthritis, psoriasis, uveitis or atherosclerosis; or wherein the inflammatory disease or IL-6-mediated condition is colitis not associated with inflammatory bowel disease. 
     
     
         33 . The method according to  claim 32 , wherein the colitis is radiation colitis, diverticular colitis, ischemic colitis, infectious colitis, celiac disease, autoimmune colitis, or colitis resulting from allergies affecting the colon.