Serum albumin binding molecules

Patent metadata

Field	Value
Publication number	US-9540424-B2
Application number	US-201414552823-A
Country	US
Kind code	B2
Filing date	Nov 25, 2014
Priority date	May 3, 2010
Publication date	Jan 10, 2017
Grant date	Jan 10, 2017

Abstract

The present invention relates to an antibody-like protein based on the tenth fibronectin type III domain ( 10 Fn3) that binds to serum albumin. The invention further relates to fusion molecules comprising a serum albumin-binding 10 Fn3 joined to a heterologous protein for use in diagnostic and therapeutic applications.

First claim

We claim:

1. A nucleic acid encoding a polypeptide comprising a fibronectin type III tenth ( 10 Fn3) domain, wherein the 10 Fn3 domain binds to domain 1 or 2 of human serum albumin with a K D of 1 μM or less, and wherein the 10 Fn3 domain comprises a modified amino acid sequence in one or more of the BC, DE and FG loops relative to the wild-type human 10 Fn3 domain (SEQ ID NO: 1), and wherein the polypeptide comprises an amino acid sequence at least 75% identical to an amino acid sequence selected from SEQ ID NOs: 4, 8, 12, 16, 20, and 24-44.

2. A vector comprising a nucleic acid of claim 1 .

3. The vector of claim 2 , wherein the vector is an expression vector.

4. A host cell comprising the vector of claim 2 .

5. The host cell of claim 4 , wherein the cell is a bacterial cell.

6. The host cell of claim 4 , wherein the cell is a mammalian cell.

7. The nucleic acid of claim 1 , which encodes a polypeptide comprising an amino acid sequence at least 80% identical to an amino acid sequence selected from the group consisting of: SEQ ID NOs: 4, 8, 12, 16, 20, and 24-44.

8. The nucleic acid of claim 7 , which encodes a polypeptide comprising an amino acid sequence at least 85% identical to an amino acid sequence selected from the group consisting of: SEQ ID NOs: 4, 8, 12, 16, 20, and 24-44.

9. The nucleic acid of claim 8 , which encodes a polypeptide comprising an amino acid sequence at least 90% identical to an amino acid sequence selected from the group consisting of: SEQ ID NOs: 4, 8, 12, 16, 20, and 24-44.

10. The nucleic acid of claim 9 , which encodes a polypeptide comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 4, 8, 12, 16, 20, and 24-44.

11. The nucleic acid of claim 1 , which encodes a polypeptide comprising an amino acid sequence at least 75% identical to the amino acid sequence of SEQ ID NO: 4.

12. The nucleic acid of claim 7 , which encodes a polypeptide comprising an amino acid sequence at least 80% identical to the amino acid sequence of SEQ ID NO: 4.

13. The nucleic acid of claim 8 , which encodes a polypeptide comprising an amino acid sequence at least 85% identical to the amino acid sequence of SEQ ID NO: 4.

14. The nucleic acid of claim 9 , which encodes a polypeptide comprising an amino acid sequence at least 90% identical to the amino acid sequence of SEQ ID NO: 4.

15. The nucleic acid of claim 10 , which encodes a polypeptide comprising the amino acid sequence of SEQ ID NO: 4.

16. A nucleic acid encoding a fusion polypeptide comprising a fibronectin type III tenth ( 10 Fn3) domain and a heterologous protein, wherein the 10 Fn3 domain binds to human serum albumin with a K D of 1 μM or less and comprises an amino acid sequence at least 75% identical to an amino acid sequence selected from the group consisting of SEQ ID NOs: 4, 8, 12, 16, 20, and 24-44.

17. The nucleic acid of claim 16 , wherein the nucleic acid comprises a sequence selected from the group consisting of SEQ ID NOs: 176-214 and 401-405.

18. The nucleic acid of claim 16 , wherein the 10 Fn3 domain comprises an amino acid sequence at least 85% identical to an amino acid sequence selected from the group consisting of SEQ ID NOs: 4, 8, 12, 16, 20, and 24-44.

19. The nucleic acid of claim 18 , wherein the 10 Fn3 domain comprises an amino acid sequence selected from SEQ ID NOs: 4, 8, 12, 16, 20, and 24-44.

Assignees

• Bristol Myers Squibb Co

Inventors

• Gosselin Michael L
• Fabrizio David
• Swain Joanna F
• Mitchell Tracy
• Camphausen Ray
• Cload Sharon T
• Furfine Eric
• Morin Paul E
• Mukerjee Ranjan
• Taylor Simeon I

Classifications

• A61P3/06

  Antihyperlipidemics · CPC title

• A61P9/00

  Drugs for disorders of the cardiovascular system · CPC title

• A61P3/10

  for hyperglycaemia, e.g. antidiabetics · CPC title

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P3/08

  for glucose homeostasis (pancreatic hormones A61P5/48) · CPC title