Fc FUSION PROTEINS COMPRISING NOVEL LINKERS OR ARRANGEMENTS

Patent metadata

Field	Value
Publication number	US-2016376346-A1
Application number	US-201615257189-A
Country	US
Kind code	A1
Filing date	Sep 6, 2016
Priority date	Apr 13, 2011
Publication date	Dec 29, 2016
Grant date	—

Abstract

The application provides Fc fusion proteins having novel arrangements. In one embodiment, the application provides Fc fusion proteins comprising a 10 F3 domain. In another embodiment, the application provides Fc fusion proteins comprising linkers derived from the naturally occurring C-terminal tail regions of membrane bound or secretory immunoglobulins.

First claim

1 . A nucleic acid encoding a polypeptide comprising:
(a) a 10 Fn3 domain having an altered amino acid sequence relative to the wild-type sequence, wherein the 10 Fn3 domain binds to a target molecule with a K D of less than 500 nM; (b) an immunoglobulin (Ig) Fc domain; and (c) a hinge sequence.

2 . The nucleic acid of claim 1 , wherein the polypeptide has one of the following arrangements from N-terminus to C-terminus: 10 Fn3 domain-hinge-Fc domain or hinge-Fc domain-linker- 10 Fn3 domain.

3 . The nucleic acid of claim 1 ,wherein the polypeptide is a dimer.

4 . The nucleic acid of claim 1 , wherein the polypeptide further comprises a second 10 Fn3 domain having an altered amino acid sequence relative to the wild-type sequence and wherein the second 10 Fn3 domain binds to a target molecule with a K D of less than 10 μM.

5 . A nucleic acid encoding a polypeptide comprising an immunoglobulin Fc domain and a heterologous polypeptide, wherein the heterologous polypeptide is fused to the N-terminus or the C-terminus of the Fc domain by a polypeptide linker, wherein the polypeptide linker comprises a sequence that is derived from the C-terminal tail region of the heavy chain of a membrane hound or secretory immunoglobulin or that is (a) at least 80% identical to any one of SEQ ID NOs: 51-54, 63-65, or 84, (b) comprises at least 5 contiguous amino acids of any one of SEQ ID NOs: 51-54, 63-65, or 84, (c) comprises at least 10 contiguous amino acids of any one of SEQ ID NOs: 51-54, 63-65, or 84, or (d) comprises any one of SEQ ID NOs: 51-54, 63-65, or 84.

6 . The nucleic acid of claim 5 , wherein the polypeptide linker comprises SEQ ID NO: 84.

7 . The nucleic acid of claim 5 , wherein the heterologous polypeptide is fused to the C-terminus of the Fc domain.

8 . The nucleic acid of claim 5 , wherein the heterologous polypeptide is fused to the N-terminus of the Fc domain.

9 . The nucleic acid of claim 5 , wherein the heterologous polypeptide comprises a 10 Fn3 domain.

10 . The nucleic acid of claim 5 , wherein the immunoglobulin Fc domain comprises a hinge or a portion thereof.

11 . A vector comprising the nucleic acid of claim 1 .

12 . A vector comprising the nucleic acid of claim 5 .

13 . A host cell comprising the vector of claim 11 .

14 . A host cell comprising the vector of claim 12 .

15 . A method of detecting a target molecule in a sample, comprising:
(a) contacting the sample with a polypeptide encoded by the nucleic acid of claim 1 , wherein said contacting is carried out under conditions that allow the polypeptide to form a complex with the target molecule; and (b) detecting the complex.

16 . A method of treating a disease or disorder comprising administering a polypeptide encoded by the nucleic acid of claim 1 to a subject in need thereof.

17 . A method of detecting a target molecule in a sample, comprising:
(a) contacting the sample with the polypeptide of claim 5 , wherein said contacting is carried out under conditions that allow the polypeptide to form a complex with the target molecule; and (b) detecting the complex.

18 . A method of treating a disease or disorder comprising administering the polypeptide of claim 5 to a subject in need thereof.

Assignees

• Bristol Myers Squibb Co

Inventors

• Camphausen Ray
• Saeed-Kothe Amna
• Davis Jonathan
• Mitchell Tracy S

Classifications

• A61K38/00

  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 title

• C07K14/78 Primary

  Connective tissue peptides, e.g. collagen, elastin, laminin, fibronectin, vitronectin or cold insoluble globulin [CIG] · CPC title

• C07K16/40

  against enzymes · CPC title

• C07K7/06

  having 5 to 11 amino acids · CPC title

• C07K7/08

  having 12 to 20 amino acids (gastrins C07K14/595; somatostatins C07K14/655; melanotropins C07K14/68) · CPC title