# US 10,865,233 B2 · NKG2D-fc for immunotherapy

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- Number: US 10,865,233 B2
- Document ID: US10865233B2
- Status: Granted
- Kind: B2
- Application number: 13/140,469
- Filed: 2009-12-18
- Published: 2011-12-22
- Granted: 2020-12-15
- Earliest claimed: 2008-12-18
- Assignees: Dana-Farber Cancer Institute, Inc.
- Applicants: Glenn Dranoff; Matthew Vanneman; Gordon Freeman
- Inventors: Glenn Dranoff; Matthew Vanneman; Gordon Freeman
- Web page: https://patentgrep.com/patent/US10865233B2

## CPC

- C07K 14/70596: {Molecules with a "CD"-designation not provided for elsewhere}
- A61K 38/177: {Receptors; Cell surface antigens; Cell surface determinants}
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61P 35/00: Antineoplastic agents
- A61P 35/02: specific for leukemia
- A61P 37/04: Immunostimulants
- C07K 14/7056: {Lectin superfamily, e.g. CD23, CD72}
- C07K 2319/30: Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto
- 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)
- 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

## Abstract

Methods for cancer immunotherapy are provided. The methods involve the use of a chimeric molecule (e.g., fusion protein) comprising an NKG2D portion and an Fc portion, which binds one or more NKG2D ligands. The methods disclosed herein are useful for the treatment of cancer that is associated with abnormal expression of one or more NKG2D ligands.

## Claims

### Claim 1

A method for treating cancer comprising:
administering to a subject having an NKG2D ligand expressing cancer a composition containing a chimeric NKG2D-Fc polypeptide and a pharmaceutically acceptable carrier, in an amount effective to treat the cancer, wherein the chimeric NKG2D-Fc polypeptide binds an NKG2D ligand, wherein the chimeric NKG2D-Fc polypeptide comprises an NKG2D extracellular domain, and wherein the chimeric NKG2D-Fc polypeptide does not include a variable domain of an antibody, a CH1 domain of an antibody, or a light chain of an antibody.

### Claim 2 (depends on 1)

The method of claim 1, wherein the chimeric NKG2D-Fc polypeptide comprises a linking molecule which is not a contiguous portion of either NKG2D or Fc and which covalently joins an amino acid of NKG2D to an amino acid of Fc.

### Claim 3 (depends on 2)

The method of claim 2, wherein the linking molecule is a peptide linker.

### Claim 4 (depends on 3)

The method of claim 3, wherein the peptide linker is an IEGR (SEQ ID NO: 1) linker.

### Claim 5 (depends on 1)

The method of claim 1, wherein the chimeric NKG2D-Fc polypeptide is a recombinant fusion protein.

### Claim 6 (depends on 5)

The method of claim 5, wherein the NKG2D ligand expressing cancer is melanoma, lung cancer, plasma cell cancer, leukemia, lymphoma, ovarian cancer, colon cancer, pancreatic cancer or prostate cancer.

### Claim 7 (depends on 5)

The method of claim 5, further comprising treating the subject with an additional cancer therapy that is not the chimeric NKG2D-Fc polypeptide, wherein the additional cancer therapy is an immunotherapy, a radiation therapy or a chemotherapy.

### Claim 8 (depends on 7)

The method of claim 7, wherein the additional cancer therapy is a chemotherapy that damages DNA.

### Claim 9 (depends on 4)

The method of claim 4, wherein the chimeric NKG2D-Fc polypeptide comprises an NKG2D extracellular domain.

### Claim 10 (depends on 4)

The method of claim 4, wherein the chimeric NKG2D-Fc polypeptide is a recombinant fusion protein.

### Claim 11 (depends on 1)

The method of claim 1, wherein the chimeric NKG2D-Fc polypeptide comprises an activating Fc domain.

### Claim 12 (depends on 11)

The method of claim 11, wherein the activating Fc domain is an activating Fc domain of an IgG.

### Claim 13 (depends on 12)

The method of claim 12, wherein the IgG is IgG1.

### Claim 14 (depends on 1)

The method of claim 1, wherein the chimeric NKG2D-Fc polypeptide further comprises a signal sequence.