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.

What is claimed is: 
     
         1 . A method of reducing the immune response elicited upon administration of a biologically active protein to a human subject, comprising:
 coupling a biologically active protein to at least one moiety capable of binding to human serum albumin to form a molecule which has a binding affinity for human 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 human serum albumin
 comprises an albumin binding domain of a surface protein from a Gram, bacterium, or a fragment or derivative thereof which at least partially retains the capability of binding albumin; 
 is capable of interacting with at least one of residues Phe-228, Ala-229, Ala-322, Val-325, Phe-326 and Met-329 in human serum albumin; and 
 comprises amino acid residues that
 contribute to the hydrophobic core of the interaction surface between human serum albumin and the moiety or contribute to the surrounding hydrogen bond interactions, and 
 correspond to residues Phe-27, Ala-31, Leu-44 and Ile-48 in the albumin binding GA module of protein PAB from  Finegoldia magna, and    
 
   wherein said molecule elicits a reduced immune response upon administration to said subject as compared to the immune response elicited upon administration to the subject of the biologically active protein that is not coupled to the moiety capable of binding to human serum albumin.   
     
     
         2 . The method according to  claim 1 , wherein the molecule has a binding affinity for human 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 human serum albumin of less than or equal to 10 −12  M. 
     
     
         4 . The method according to  claim 1 , wherein the immune response is a humoral immune response. 
     
     
         5 . 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. 
     
     
         6 . The method according to  claim 5 , wherein the biological activity of the biologically active protein comprises an ability to block the activity of the target molecule. 
     
     
         7 . The method according to  claim 5 , wherein the target molecule is present on the surface of a cell. 
     
     
         8 . The method according to  claim 7 , wherein the cell is a cancerous or precancerous cell. 
     
     
         9 . The method according to  claim 7 , wherein the target molecule present on the surface of the cell is selected from HER2, CD4, CD20, CD22, CD74, CEA and EpCAM. 
     
     
         10 . The method according to  claim 5 , wherein the target molecule is an enzyme. 
     
     
         11 . The method according to  claim 5 , wherein the target molecule is selected from hormone receptors and cytokine receptors. 
     
     
         12 . The method according to  claim 1 , wherein the biologically active protein is selected from antibodies, staphylococcal protein A, fibronectin, lipocalin, transferrin, and lectin. 
     
     
         13 . The method according to  claim 1 , wherein the biological activity of the biologically active protein comprises an enzymatic activity. 
     
     
         14 . The method according to  claim 1 , wherein the biological activity of the biologically active protein comprises a hormone activity. 
     
     
         15 . The method according to  claim 1 , wherein the biological activity of the biologically active protein comprises a pharmaceutical activity. 
     
     
         16 . 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, GLP1 and thrombopoietin.