Antigen-binding proteins comprising recombinant protein scaffolds

Patent metadata

Field	Value
Publication number	US-10583166-B2
Application number	US-201715587441-A
Country	US
Kind code	B2
Filing date	May 5, 2017
Priority date	Mar 31, 2009
Publication date	Mar 10, 2020
Grant date	Mar 10, 2020

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 a glucocorticoid-induced tumor necrosis factor receptor ligand (GITRL) or a portion thereof and a 4D5 antibody-derived fragment single chain Fv region (4D5-scFv), wherein the multifunctional antigen-binding protein comprises the amino acid sequence of SEQ ID NO: 11.

2. The multifunctional antigen-binding protein of claim 1 , wherein the GITRL is linked to the 4D5-scFv and is also capable of binding to a protein other than that bound by the 4D5-scFv.

3. The multifunctional antigen-binding protein of claim 1 , wherein the GITRL comprises the amino acid sequence of SEQ ID NO: 4.

4. The multifunctional antigen-binding protein of claim 1 , further 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.

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

12. A method of treating a disease associated with Her2/neu expression in a subject comprising, administering a therapeutic amount of the multifunctional antigen-binding protein of claim 1 to the subject.

13. A method of detecting a Her2/neu receptor in a subject comprising, administering the multifunctional antigen-binding protein of claim 1 to the subject and detecting binding of the multifunctional antigen-binding protein to Her2/neu receptor.

14. 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 the multifunctional antigen-binding protein to the sample.

Assignees

• Univ Pennsylvania

Inventors

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

Classifications

• A61P35/00

  Antineoplastic agents · CPC title

• C07K16/2896

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

• G01N33/53

  Immunoassay; Biospecific binding assay; Materials therefor · CPC title

• A61K49/00

  Preparations for testing in vivo · CPC title

• C07K14/70596

  Molecules with a "CD"-designation not provided for elsewhere · CPC title