Targeted heterodimeric Fc fusion proteins containing IL-15 IL-15alpha and antigen binding domains

Patent metadata

Field	Value
Publication number	US-12139525-B2
Application number	US-202117366565-A
Country	US
Kind code	B2
Filing date	Jul 2, 2021
Priority date	Jun 30, 2017
Publication date	Nov 12, 2024
Grant date	Nov 12, 2024

Abstract

The present invention is directed to a novel targeted heterodimeric Fc fusion proteins comprising an IL-15/IL-15Rα Fc fusion protein and an antigen binding domain Fc fusion proteins. In some instances, the antigen binding domain binds to CD8, NKG2A, or NKG2D.

First claim

What is claimed is:

1. An anti-CD8 binding domain, said anti-CD8 binding domain comprising:
a) a variable heavy chain domain having the amino acid sequence of SEQ ID NO: 877 or SEQ ID NO: 881; and
b) a variable light chain domain having the amino acid sequence of SEQ ID NO: 917.

2. The anti-CD8 binding domain of claim 1 , wherein said anti-CD8 binding domain comprises a variable heavy chain domain having the amino acid sequence of SEQ ID NO: 877 and a variable light chain domain having the amino acid sequence of SEQ ID NO: 917.

3. The anti-CD8 binding domain of claim 1 , wherein said anti-CD8 binding domain comprises a variable heavy chain domain having the amino acid sequence of SEQ ID NO: 881 and a variable light chain domain having the amino acid sequence of SEQ ID NO: 917.

4. The anti-CD8 binding domain of claim 1 , wherein said anti-CD8 binding domain further comprises a scFv linker that covalently attaches said variable heavy chain domain and variable light chain domain to form an scFv domain.

5. The anti-CD8 binding domain of claim 1 , wherein said anti-CD8 binding domain further comprises an Fc domain selected from the group consisting of a human IgG1, IgG2 and IgG4 Fc domain.

6. The anti-CD8 binding domain of claim 5 , wherein said Fc domain is a variant human Fc domain selected from the group consisting of a variant human IgG1 Fc domain, a variant human IgG2 Fc domain, and a variant human IgG4 Fc domain.

7. A fragment antigen binding (Fab) domain comprising the anti-CD8 binding domain of claim 1 .

8. An antibody comprising the anti-CD8 binding domain of claim 1 .

9. A nucleic acid composition comprising:
a) a first nucleic acid encoding a variable heavy chain domain having the amino acid sequence of SEQ ID NO: 877 or SEQ ID NO: 881, and
b) a second nucleic acid encoding a variable light chain domain having the amino acid sequence of SEQ ID NO: 917.

10. An expression vector composition comprising:
a) a first expression vector comprising said first nucleic acid of claim 9 ; and
b) a second expression vector comprising said second nucleic acid of claim 9 .

11. A host cell comprising said expression vector composition of claim 10 .

12. A method of making an anti-CD8 binding domain, the method comprising culturing the host cell of claim 11 under conditions wherein said anti-CD8 binding domain is expressed, and recovering said anti-CD8 binding domain.

13. A method of treating cancer in a patient in need thereof comprising administering a therapeutically effective amount of the anti-CD8 binding domain of claim 1 to said patient.

Assignees

• Xencor Inc

Inventors

• Bernett Matthew J
• Desjarlais John
• Varma Rajat
• Schubbert Suzanne
• Diaz Juan

Classifications

• C12N15/63

  Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression · CPC title

• A61K38/2086

  IL-13 to IL-16 · CPC title

• A61K38/1774

  Immunoglobulin superfamily (e.g. CD2, CD4, CD8, ICAM molecules, B7 molecules, Fc-receptors, MHC-molecules) · CPC title

• A61K39/395

  Antibodies (agglutinins A61K38/36 {; as drug carriers A61K47/50}); Immunoglobulins; Immune serum, e.g. antilymphocytic serum · CPC title

• C12N15/62

  DNA sequences coding for fusion proteins · CPC title