Serum albumin-binding fibronectin type III domains

• US 10,442,851 B2
• Filed: 03/19/2015
• Issued: 10/15/2019
• Est. Priority Date: 03/20/2014
• Status: Active Grant

• Current Assignee: Bristol-Myers Squibb Company
• Original Assignee: Bristol-Myers Squibb Company
• Inventors: Mitchell, Tracy S., Gosselin, Michael L., Lipovsek, Dasa, Parker, Rex, Camphausen, Ray, Davis, Jonathan, Fabrizio, David
• Primary Examiner(s): Haddad, Maher M
• Application Number:
  US15/127,166
• Publication Number:
  US 20170174748A1
• Time in Patent Office: 1,671 Days
• Field of Search: None
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: A61K 47/64 Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent peptidic linkers A61K47/65
• CPC Class Codes: C07K 14/78 Connective tissue peptides, e.g. collagen, elastin, laminin, fibronectin, vitronectin or cold insoluble globulin [CIG]
• CPC Class Codes: C07K 2319/00 Fusion polypeptide
• CPC Class Codes: C07K 2319/70 containing domain for protein-protein interaction

Abstract

The present invention relates to polypeptides which include tenth fibronectin type III domains (¹⁰Fn3) that binds to serum albumin, with south pole loop substitutions. The invention further relates to fusion molecules comprising a serum albumin-binding ¹⁰Fn3 joined to a heterologous protein for use in diagnostic and therapeutic applications.

Claims

1. A polypeptide comprising a fibronectin type III tenth domain (¹⁰Fn3) wherein the amino acid sequence of the CD loop of the wild-type ¹⁰Fn3 domain set forth in SEQ ID NO:

1 is replaced by an amino acid sequence selected from the group consisting of SEQ ID NOs;

101-125, and wherein the polypeptide binds to human serum albumin, and to one or more of rhesus serum albumin, cynomolgus serum albumin, mouse serum albumin, and rat serum albumin.

2. The polypeptide of claim 1, wherein the polypeptide is a fusion polypeptide comprising a heterologous protein.

3. The fusion polypeptide of claim 2, wherein the heterologous protein is a therapeutic moiety.

4. The fusion polypeptide of claim 2, wherein the heterologous protein is a polypeptide comprising a ¹⁰Fn3 domain.

5. The fusion polypeptide of claim 4, wherein the ¹⁰Fn3 domain of the heterologous protein binds to a target protein other than serum albumin.

11. A composition comprising the polypeptide of claim 1 and a carrier.

6. A polypeptide comprising an amino acid sequence selected from the group consisting of SEQ ID NOs:

23-30, 32-40, 42-56, 58-66, 68-82, 84-92, 94-100, 184-191, 193-201, 203-209, 235-242, 243-252 and 254-260, wherein the polypeptide binds to human serum albumin, and to one or more of rhesus serum albumin, cynomolgus serum albumin, mouse serum albumin, and rat serum albumin.

7. The polypeptide of claim 6, wherein the polypeptide is a fusion polypeptide comprising a heterologous protein.

8. The fusion polypeptide of claim 7, wherein the heterologous protein is a therapeutic moiety.

9. The fusion polypeptide of claim 7, wherein the heterologous protein is a polypeptide comprising a ¹⁰Fn3 domain.

10. The fusion polypeptide of claim 8, wherein the ¹⁰Fn3 domain of the heterologous protein binds to a target protein other than serum albumin.

12. A composition comprising the polypeptide of claim 6 and a carrier.