Antigen-binding proteins comprising recombinant protein scaffolds

Patent metadata

Field	Value
Publication number	US-9695252-B2
Application number	US-201414243614-A
Country	US
Kind code	B2
Filing date	Apr 2, 2014
Priority date	Mar 31, 2009
Publication date	Jul 4, 2017
Grant date	Jul 4, 2017

Abstract

Disclosed herein are recombinant protein scaffolds and recombinant multifunctional protein scaffolds for use in producing antigen-binding proteins In addition, nucleic acids encoding such recombinant protein scaffolds, recombinant multifunctional protein scaffolds, and antigen-binding proteins are provided Vectors and cells useful for expression of the described proteins are also provided, as are methods of use.

First claim

What is claimed:

1. A multifunctional antigen-binding protein, comprising:
at least one multifunctional recombinant protein scaffold comprising an amino acid sequence selected from the group consisting of SEQ ID NO:2, SEQ ID NO:3, or SEQ ID NO:4,
at least one recombinant protein scaffold comprising the amino acid sequence of SEQ ID NO: 1, and
at least one antigen-specific peptide comprising an amino acid sequence selected from the group consisting of SEQ ID NOs:12-24.

2. The multifunctional antigen-binding protein of claim 1 , wherein said at least one multifunctional recombinant protein scaffold is linked to said antigen-specific peptide and is also capable of binding to a protein other than that bound by said antigen-specific peptide.

3. The multifunctional antigen-binding protein of claim 1 , wherein said at least one recombinant protein scaffold is linked to said antigen-specific peptide, and said at least one multifunctional recombinant protein scaffold is capable of binding to a protein other than that bound by said antigen-specific peptide.

4. The multifunctional antigen-binding protein of claim 1 , comprising a protein domain that promotes solubility.

5. The multifunctional antigen-binding protein of claim 1 , further comprising an epitope tag, a fluorophore, a radio isotope, or an enzyme.

6. The multifunctional antigen-binding protein of claim 5 , wherein said epitope tag is a poly-histidine tag.

7. A polynucleotide encoding the multifunctional antigen-binding protein of claim 1 .

8. A cell that has been genetically engineered to express the polynucleotide of claim 7 .

9. A composition comprising the multifunctional antigen-binding protein claim 1 and a pharmaceutically acceptable carrier.

10. The multifunctional antigen-binding protein of claim 1 , further comprising a linker having one or more glycine residues that connects said at least one multifunctional recombinant protein scaffold, said at least one recombinant protein scaffold, or said at least one antigen-specific peptide to another component of the multifunctional antigen-binding protein.

11. The multifunctional antigen-binding protein of claim 10 , wherein the linker comprises SEQ ID NO:25 or SEQ ID NO:26.

12. A method of treating disease in a subject comprising, administering a therapeutic amount of the multifunctional antigen-binding protein of claim 1 to a subject in need thereof.

13. A method of treating a disease associated with the Her2/neu receptor in a subject, comprising administering to the subject a composition including the multifunctional antigen-binding protein of claim 1 and a pharmaceutically acceptable carrier.

14. A method of detecting an antigen of interest in a subject comprising, administering the multifunctional antigen-binding protein of claim 1 to a subject and detecting binding of said multifunctional antigen-binding protein to said antigen of interest.

15. A method of detecting the Her2/neu receptor, comprising exposing a sample containing the Her2/neu receptor to the multifunctional antigen-binding protein of claim 1 and detecting binding of said multifunctional antigen-binding protein to said sample.

Assignees

• Univ Pennsylvania

Inventors

• Greene Mark I
• Zhang Hongtao
• Song Xiaomin
• Murali Ramachandran
• Tone Masahide

Classifications

• A61P35/00

  Antineoplastic agents · CPC title

• A61K49/00

  Preparations for testing in vivo · CPC title

• A61K38/16 Primary

  Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof {(enzyme inhibitors A61K38/005)} · CPC title

• C07K16/2896

  against molecules with a "CD"-designation, not provided for elsewhere · CPC title

• C07K2319/30

  Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto · CPC title