Method for reducing the immune response to a biologically active protein

Abstract

A new use of a molecule comprising at least one moiety which is a biologically active protein and at least one moiety capable of binding to a serum albumin of a mammal is provided, for preparation of a medicament which elicits no or a reduced immune response upon administration to the mammal, as compared to the immune response elicited upon administration to the mammal of the biologically active protein per se. Also provided is a method of reducing or eliminating the immune response elicited upon administration of a biologically active protein to a human or non-human mammal, which comprises coupling the polypeptide to at least one moiety capable of binding to a serum albumin of the mammal.

1 . A method of reducing the immune response elicited upon administration of a biologically active protein to a mammal, comprising
 coupling a biologically active protein to at least one moiety capable of binding to a serum albumin of a mammal to form a molecule which has a binding affinity for the serum albumin such that the K D  of the interaction is less than or equal to 10 −7  M,   wherein the moiety capable of binding to a serum albumin of a mammal is the 46 amino acid ABD domain of streptococcal protein G or an albumin binding derivative thereof having from 40 to 53 amino acid residues, and   wherein said molecule elicits a reduced immune response upon administration to said mammal as compared to the immune response elicited upon administration to the mammal of the biologically active protein that is not coupled to the moiety capable of binding to a serum albumin of a mammal.   
     
     
         2 . The method according to  claim 1 , wherein the molecule has a binding affinity for serum albumin of less than or equal to 10 −9  M. 
     
     
         3 . The method according to  claim 2 , wherein the molecule has a binding affinity for serum albumin of less than or equal to 10 −12  M. 
     
     
         4 . The method of  claim 1 , wherein the mammal is a human being. 
     
     
         5 . The method according to  claim 1 , wherein the mammal is a non-human mammal. 
     
     
         6 . The method according to  claim 1 , wherein the immune response is a humoral immune response. 
     
     
         7 . The method according to  claim 1 , wherein the biological activity of the biologically active protein comprises an ability to interact with a target molecule other than a serum albumin. 
     
     
         8 . The method according to  claim 7 , wherein the biological activity of the biologically active protein comprises an ability to block the activity of the target molecule. 
     
     
         9 . The method according to  claim 7 , wherein the target molecule is present on the surface of a cell. 
     
     
         10 . The method according to  claim 9 , wherein the cell is a cancerous or precancerous cell. 
     
     
         11 . The method according to  claim 10 , wherein the target molecule present on the surface of the cell is selected from HER2, CD4, CD20, CD22, CD74, CEA and EpCAM. 
     
     
         12 . The method according to  claim 7 , wherein the target molecule is an enzyme. 
     
     
         13 . The method according to  claim 7 , wherein the target molecule is selected from hormone receptors and cytokine receptors. 
     
     
         14 . The method according to  claim 1 , wherein the biologically active protein is selected from antibodies, staphylococcal protein A, fibronectin, lipocalin, transferrin, and lectin. 
     
     
         15 . The method according to  claim 1 , wherein the biological activity of the biologically active protein comprises an enzymatic activity. 
     
     
         16 . The method according to  claim 1 , wherein the biological activity of the biologically active protein comprises a hormone activity. 
     
     
         17 . The method according to  claim 1 , wherein the biologically active protein is selected from growth hormone, ciliary neurotrophic factor, granulocyte-macrophage colony stimulating factor, insulin, interferon β, factor VIII, erythropoietin, GL1P and thrombopoietin. 
     
     
         18 . A molecule comprising at least one moiety which is a biologically active protein and at least one moiety capable of binding to a serum albumin of a mammal, wherein the molecule elicits a reduced immune response upon administration to the mammal, as compared to the immune response elicited upon administration to the mammal of the biologically active protein that is not coupled to at least one moiety capable of binding to a serum albumin of the mammal,
 wherein said moiety capable of binding to a serum albumin of a mammal is the 46 amino acid ABD domain of streptococcal protein G or an albumin binding derivative thereof having from 40 to 53 amino acid residues, and   wherein said molecule has a binding affinity for the serum albumin such that the K D  of the interaction is less than or equal to 10 −7  M.   
     
     
         19 . The molecule according to  claim 18 , which has a binding affinity for serum albumin of less than or equal to 10 −9  M. 
     
     
         20 . The molecule according to  claim 19 , which has a binding affinity for serum albumin of less than or equal to 10 −12  M.