SAP FC fusion proteins and methods of use
View Patent ↗The present invention relates to SAP-Fc fusion proteins comprising one or more amino acid substitution, for example, C226S and/or C229S. In some aspects, the fusion protein comprises a structure represented by the following formula, from N-terminus to C-terminus, SAP-Fc1-L1-Fc2, wherein Fc1 is a first Fc domain sequence comprising hinge-CH2-CH3, L1 is a linker, and Fc2 is a second Fc domain sequence comprising hinge-CH2-CH3. The present invention also relates to methods of treating amyloid related diseases by administering said SAP-Fc fusion proteins to a subject in need thereof.
1. A fusion protein comprising a structure represented by the following formula, from N-terminus to C-terminus, SAP-Fc1-L1-Fc2, wherein Fc1 is a first Fc domain sequence comprising hinge-CH2-CH3, L1 is a linker, and Fc2 is a second Fc domain sequence comprising hinge-CH2-CH3, wherein SAP is a human serum amyloid P (SAP) component protein, wherein Fc1 and Fc2 each comprise amino acid substitutions C226S and C229S, according to EU numbering, wherein the fusion protein comprises the amino acid sequence set forth in SEQ ID NO: 1 with or without the C-terminal lysine, or SEQ ID NO: 23 with or without the C-terminal lysine.
2. A fusion protein comprising a structure represented by the following formula, from N-terminus to C-terminus, SAP-Fc1-L1-Fc2, wherein Fc1 is a first Fc domain sequence comprising hinge-CH2-CH3, L1 is a linker, and Fc2 is a second Fc domain sequence comprising hinge-CH2-CH3, wherein SAP is a human serum amyloid P (SAP) component protein, wherein Fc1 and Fc2 each comprise amino acid substitutions C226S and C229S, according to EU numbering, wherein the human SAP comprises the amino acid sequence set forth in SEQ ID NO: 20.
3. The fusion protein of claim 2 , wherein Fc1 and Fc2 each comprise the amino acid sequence set forth in SEQ ID NO: 18.
4. The fusion protein of claim 2 , wherein the Fc1 or Fc2 comprises a mutation that reduces FcRn binding.
5. The fusion protein of claim 1 , wherein the fusion protein forms a pentamer or a decamer.
6. The fusion protein of claim 1 , wherein the fusion protein has reduced aggregation compared to a fusion protein lacking the amino acid substitutions.
7. A pharmaceutical composition comprising the fusion protein of claim 1 , and a pharmaceutically acceptable carrier.
8. The fusion protein of claim 1 , wherein the fusion protein is produced by a method comprising culturing a host cell comprising nucleic acid encoding the fusion protein under conditions to express the fusion protein.
9. The fusion protein of claim 2 , wherein L1 comprises the amino acid sequence set forth in SEQ ID NO: 19.
10. The fusion protein of claim 3 , wherein L1 comprises the amino acid sequence set forth in SEQ ID NO:19.
11. The fusion protein of claim 2 , wherein the fusion protein forms a pentamer or a decamer.
12. The fusion protein of claim 2 , wherein the Fc1 and Fc2 are human Fc domains.
13. The fusion protein of claim 12 , wherein the Fc1 and Fc2 are human IgG1 Fc domains.
14. The fusion protein of claim 2 , wherein the fusion protein has reduced aggregation compared to a fusion protein lacking the amino acid substitutions.
15. A pharmaceutical composition comprising the fusion protein of claim 2 , and a pharmaceutically acceptable carrier.
16. The fusion protein of claim 2 , wherein the fusion protein is produced by a method comprising culturing a host cell comprising nucleic acid encoding the fusion protein under conditions to express the fusion protein.
17. The fusion protein of claim 1 , wherein the fusion protein comprises the amino acid sequence set forth in SEQ ID NO: 1 with or without the C-terminal lysine.
18. The fusion protein of claim 1 , wherein the fusion protein comprises the amino acid sequence set forth in SEQ ID NO: 23 with or without the C-terminal lysine.
19. The fusion protein of claim 2 , wherein the Fc1 and Fc2 each comprise
the amino acid sequence set forth in SEQ ID NO: 21.