Method for reducing the immune response to a biologically active protein
View Patent ↗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 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, 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.
2. The method of claim 1 , in which the ABD domain is arranged to enhance its binding with human serum albumin.
3. The method according to claim 2 in which the ABD domain 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.
4. The method according to claim 2 in which the ABD domain 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.
5. The method according to claim 2 in which the ABD domain 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.
6. The method according to claim 1 , wherein the molecule has a binding affinity for the serum albumin of less than or equal to 10 −8 M.
7. The method according to claim 6 , wherein the molecule has a binding affinity for the serum albumin of less than or equal to 10 −9 M.
8. The method of claim 1 , wherein the mammal is a human being.
9. The method according to claim 1 , wherein the mammal is a non-human mammal.
10. The method according to claim 1 , wherein the immune response is a humoral immune response.
11. 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.
12. The method according to claim 11 , wherein the biological activity of the biologically active protein comprises an ability to block the activity of the target molecule.
13. The method according to claim 11 , wherein the target molecule is present on the surface of a cell.
14. The method according to claim 13 , wherein the cell is a cancerous or precancerous cell.
15. The method according to claim 14 , wherein the target molecule present on the surface of the cell is selected from HER2, CD4, CD20, CD22, CD74, CEA and EpCAM.
16. The method according to claim 11 , wherein the target molecule is selected from hormone receptors and cytokine receptors.
17. The method according to claim 1 , wherein the biologically active protein is selected from antibodies, staphylococcal protein A, fibronectin, lipocalin, transferrin, and lectin.
18. The method according to claim 17 , wherein the biologically active protein is staphylococcal protein A.
19. The method according to claim 18 , wherein the biologically active protein comprises the B domain of staphylococcal protein A.