# US 12,599,650 B2 · Inhibition of SIRP-gamma for cancer treatment

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- Number: US 12,599,650 B2
- Document ID: US12599650B2
- Status: Granted
- Kind: B2
- Application number: 17/618,922
- Filed: 2020-06-23
- Published: 2022-09-29
- Granted: 2026-04-14
- Earliest claimed: 2019-06-24
- Assignees: Amgen Inc.
- Applicants: Amgen Inc.
- Inventors: Ruozhen Hu; Paolo Manzanillo; Wenjun Ouyang
- Web page: https://patentgrep.com/patent/US12599650B2

## CPC

- A61K 38/1774: {Immunoglobulin superfamily (e.g. CD2, CD4, CD8, ICAM molecules, B7 molecules, Fc-receptors, MHC-molecules)}
- A61K 38/177: {Receptors; Cell surface antigens; Cell surface determinants}
- A61K 47/02: Inorganic compounds
- A61P 35/00: Antineoplastic agents
- C07K 16/2803: {against the immunoglobulin superfamily}
- C07K 2317/76: Antagonist effect on antigen, e.g. neutralization or inhibition of binding
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00)

## Abstract

Provided herein are methods of treating a subject with a tumor or cancer. In exemplary embodiments, the method comprises increasing an immune response against the tumor or cancer in the subject or increasing effector activity or reducing suppressive activity of T-cells in the subject. In exemplary embodiments, the method comprises administering to the subject a SIRPγ binder, e.g., SIRPγ inhibitor, in an amount effective to treat the tumor or cancer in the subject.

## Claims

### Claim 1

A method of treating a subject with a tumor or cancer, the method comprising administering to the subject an anti-signal regulatory protein gamma (SIRPγ) antibody comprising a means for binding SIRPγ at the interface between Immunoglobulin (Ig) Domain 1 (D1) and Ig Domain 2 (D2) of SIRPγ, in an amount effective to treat the tumor or cancer in the subject.

### Claim 2 (depends on 1)

The method of claim 1, wherein the anti-SIRPγ antibody is a SIRPγ inhibitor.

### Claim 3 (depends on 2)

The method of claim 2, wherein the anti-SIRPγ antibody reduces a binding interaction between SIRPγ and a SIRPγ binding partner.

### Claim 4 (depends on 3)

The method of claim 3, wherein the SIRPγ binding partner is CD47.

### Claim 5 (depends on 1)

The method of claim 1, wherein the anti-SIRPγ antibody is OX117 or an antigen-binding fragment thereof.

### Claim 6 (depends on 1)

The method of claim 1, wherein the anti-SIRPγ antibody forms hydrogen bonds with one or more of amino acid residues Q8, E10, G109, K11, L12, and D149 of SIRPγ (SEQ ID NO: 3).

### Claim 7 (depends on 1)

The method of claim 1, wherein the anti-SIRPγ antibody simultaneously binds to two SIRPγ molecules or promotes SIRPγ dimerization.

### Claim 8 (depends on 1)

The method of claim 1, wherein the anti-SIRPγ antibody binds to an epitope which does not overlap with the CD47 binding site of SIRPγ.

### Claim 9 (depends on 1)

The method of claim 1, wherein the anti-SIRPγ antibody forms hydrogen bonds with one or more of amino acid residues Q8, E10, G109, K11, L12, and D149 at the interface between Immunoglobulin (Ig) Domain 1 (D1) and Ig Domain 2 (D2) of SIRPγ (SEQ ID NO: 3).