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 - 108 . (canceled) 
     
     
         109 . A method of reducing or eliminating the immune response elicited upon administration of a biologically active protein to a mammal, comprising coupling said biologically active protein to at least one moiety capable of binding to a serum albumin of a mammal, 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 about 40 to 53 amino acid residues, 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, and wherein said molecule is capable of reducing or eliminating the immune response elicited upon administration of said biologically active protein to said mammal. 
     
     
         110 . The method of  claim 109 , in which the ABD domain or derivative thereof is arranged to enhance its binding with human serum albumin. 
     
     
         111 . The method according to  claim 110 , in which the ABD domain or derivative thereof is capable of interacting at least one of, and preferably all of, residues Phe-228, Ala-229, Ala-322, Val-325, Phe-326, and Met-329 from human serum albumin so as to enhance binding of the molecule to albumin. 
     
     
         112 . The method according to  claim 111 , in which the ABD domain or derivative thereof includes an amino acid residue which forms an interaction with the methionine residue at position 329 of human serum albumin so as to enhance binding of the molecule to albumin. 
     
     
         113 . The method according to  claim 110 , in which the ABD domain or derivative thereof includes an amino acid residue which forms an interaction with helix 7 in the human serum albumin domain IIB so as to enhance binding of the molecule to albumin. 
     
     
         114 . The method according to  claim 110 , in which the ABD domain or derivative thereof includes an amino acid residue which forms an interaction with residues in human serum albumin domain IIA so as to enhance binding of the molecule to albumin. 
     
     
         115 . The method according to  claim 110 , in which the ABD domain or derivative thereof includes an amino acid residue which forms an interaction with residues between helices 2 and 3 of human serum albumin so as to enhance binding of the molecule to albumin. 
     
     
         116 . The method according to  claim 109 , wherein the molecule has a binding affinity for serum albumin of less than or equal to 10 −8  M. 
     
     
         117 . The method according to  claim 116 , wherein the molecule has a binding affinity for serum albumin of less than or equal to 10 −9  M. 
     
     
         118 . The method according to  claim 117 , wherein the molecule has a binding affinity for serum albumin of less than or equal to 10 −10  M. 
     
     
         119 . The method according to  claim 118 , wherein the molecule has a binding affinity for serum albumin of less than or equal to 10 −11  M. 
     
     
         120 . The method according to  claim 119 , wherein the molecule has a binding affinity for serum albumin of less than or equal to 10 −12  M. 
     
     
         121 . The method according to  claim 120 , wherein the molecule has a binding affinity for serum albumin of less than or equal to 10 −13  M. 
     
     
         122 . The method according to  claim 121 , wherein the molecule has a binding affinity for serum albumin of less than or equal to 10 −14  M. 
     
     
         123 . The method of  claim 109 , wherein the mammal is a human being. 
     
     
         124 . The method according to  claim 109 , wherein the mammal is a non-human mammal. 
     
     
         125 . The method according to  claim 109 , wherein the immune response is a humoral immune response. 
     
     
         126 . The method according to  claim 109 , wherein the biological activity of the biologically active protein comprises an ability to interact with a target molecule other than a serum albumin. 
     
     
         127 . The method according to  claim 126 , wherein the biological activity of the biologically active protein comprises an ability to block the activity of the target molecule. 
     
     
         128 . The method according to  claim 126 , wherein the target molecule is present on the surface of a cell. 
     
     
         129 . The method according to  claim 128 , wherein the cell is a cancerous or precancerous cell. 
     
     
         130 . The method according to  claim 129 , wherein the target molecule present on the surface of the cell is selected from HER2, CD4, CD20, CD22, CD74, CEA and EpCAM. 
     
     
         131 . The method according to  claim 126 , wherein the target molecule is an enzyme. 
     
     
         132 . The method according to  claim 126 , wherein the target molecule is selected from hormone receptors and cytokine receptors. 
     
     
         133 . The method according to  claim 126 , wherein the target molecule is a toxin. 
     
     
         134 . The method according to  claim 133 , in which the toxin is a snake toxin. 
     
     
         135 . The method according to  claim 109 , wherein the biologically active protein is selected from antibodies, staphylococcal protein A, fibronectin, lipocalin, transferrin, and lectin. 
     
     
         136 . The method according to  claim 135 , wherein the biologically active protein is staphylococcal protein A. 
     
     
         137 . The method according to  claim 136 , wherein the biologically active protein comprises the B domain of staphylococcal protein A. 
     
     
         138 . The method according to  claim 109 , wherein the biological activity of the biologically active protein comprises an enzymatic activity. 
     
     
         139 . The method according to  claim 109 , wherein the biological activity of the biologically active protein comprises a hormone activity. 
     
     
         140 . The method according to  claim 109 , wherein the biological activity of the biologically active protein comprises a pharmaceutical activity. 
     
     
         141 . The method according to  claim 109 , 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.