# US 7,410,767 B1 · HLA-E binding

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- Number: US 7,410,767 B1
- Document ID: US7410767B1
- Status: Granted
- Kind: B1
- Application number: 09/555,555
- Filed: 1998-12-04
- Granted: 2008-08-12
- Earliest claimed: 1997-12-04
- Assignees: Isis Innovation Limited
- Inventors: Veronique M. Braud; David S. J. Allan; Graham S. Ogg; Christopher A. O'Callaghan; Andrew J. McMichael
- Web page: https://patentgrep.com/patent/US7410767B1

## CPC

- C07K 16/2896: {against molecules with a "CD"-designation, not provided for elsewhere}
- A61P 15/00: Drugs for genital or sexual disorders (for disorders of sex hormones A61P5/24); Contraceptives
- A61P 15/08: for gonadal disorders or for enhancing fertility, e.g. inducers of ovulation or of spermatogenesis
- A61P 31/00: Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P 31/12: Antivirals
- A61P 31/18: for HIV
- A61P 31/22: for herpes viruses
- A61P 35/00: Antineoplastic agents
- A61P 35/02: specific for leukemia
- A61P 37/00: Drugs for immunological or allergic disorders
- A61P 37/02: Immunomodulators
- A61P 37/04: Immunostimulants
- A61P 37/06: Immunosuppressants, e.g. drugs for graft rejection
- C07K 16/2851: {against the lectin superfamily, e.g. CD23, CD72}
- G01N 33/56977: {HLA or MHC typing}
- C07K 2317/76: Antagonist effect on antigen, e.g. neutralization or inhibition of binding
- G01N 2333/70539: MHC-molecules, e.g. HLA-molecules
- G01N 2333/7056: Selectin superfamily, e.g. LAM-1, GlyCAM, ELAM-1, PADGEM
- 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)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q)

## Abstract

The invention relates to a method of testing a compound for biological activity, which method comprises providing cells expressing one of the CD94/NKG2 family of receptors, contacting the cells with recombinant HLA-E under binding conditions in the presence of the test compound, and determining whether the presence of the compound affects the binding of HLA-E to the cells. The HLA-E property of binding to CD94/NKG2 receptors on NK cells and a subset of CD8+ T cells is useful for targeting CD94/NKG2+ cells for a variety of purposes such as identification, isolation, killing or inactivation.

## Claims

### Claim 1

A method of testing a compound for biological activity, which method comprises:
(i) providing cells expressing a CD94/NKG2 receptor, wherein the NKG2 member is selected from the group consisting of NKG2A, NKG2B, NKG2C, NKG2E, and NKG2F at the cell surface;
(ii) contacting the cells with HLA-E in the presence of the test compound; and
(iii) determining whether the presence of the compound affects the binding of HLA-E to the cells.

### Claim 2 (depends on 1)

The method according to claim 1, wherein the CD94/NKG2 receptor is an inhibitory NK cell receptor.

### Claim 3 (depends on 1)

The method according to claim 1, wherein the CD94/NKG2 receptor is a stimulatory NK cell receptor.

### Claim 4 (depends on 1)

The method according to claim 1, wherein the NKG2 member is NKG2A.

### Claim 5 (depends on 1)

The method according to claim 1, wherein the NKG2 member is NKG2C.

### Claim 6 (depends on 1)

The method according to claim 1, wherein the NKG2 member is NKG2B.

### Claim 7 (depends on 1)

The method according to claim 1, wherein the NKG2 member is NKG2E.

### Claim 8 (depends on 1)

The method according to claim 1, wherein the NKG2 member is NKG2F.

### Claim 9 (depends on 1)

The method of claim 1, wherein the test compound is an antibody.

### Claim 10

A method of identifying a compound affecting the binding of HLA-E to CD94/NKG2 receptors, which method comprises:
(i) providing cells expressing a CD94/NKG2 receptor at the cell surface, wherein the NKG2 member is selected from a group consisting of NKG2A, NKG2B, NKG2C, NKG2E, and NKG2F;
(ii) contacting the cells with HLA-E in the presence of a test compound; and
(iii) determining whether the presence of the compound affects the binding of HLA-E to the cells.

### Claim 11 (depends on 10)

The method of claim 10, further comprising using the identified compounds in therapeutic applications, wherein the identified compounds are antibodies.

### Claim 12 (depends on 10)

The method of claim 10, wherein the CD94/NKG2 receptor is an inhibitory NK cell receptor.

### Claim 13 (depends on 10)

The method of claim 10, wherein the CD94/NKG2 receptor is a stimulatory NK cell receptor.

### Claim 14 (depends on 10)

The method of claim 10, wherein the NKG2 member is NKG2A.

### Claim 15 (depends on 10)

The method of claim 10, wherein the NKG2 member is NKG2C.

### Claim 16 (depends on 10)

The method of claim 10, wherein the test compound is an antibody.

### Claim 17

A method for screening and producing an identified compound which affects the binding of HLA-E to CD94/NKG2 receptors, which method comprises:
(i) selecting a test compound for screening;
(ii) providing cells expressing a CD94/NKG2 receptor at the cell surface, wherein the NKG2 member is selected from a group consisting of NKG2A, NKG2B, NKG2C, NKG2E, and NKG2F;
(iii) contacting the cells with HLA-E in the presence of the test compound;
(iv) determining whether the presence of the test compound affects the binding of HLA-E to the cells thereby providing an identified compound; and
(v) producing the identified compound which affects the binding of HLA-E to the cells.

### Claim 18 (depends on 17)

The method of claim 17, wherein the CD94/NKG2 receptor is an inhibitory NK cell receptor.

### Claim 19 (depends on 17)

The method of claim 17, wherein the CD94/NKG2 receptor is a stimulatory NK cell receptor.

### Claim 20 (depends on 17)

The method of claim 17, wherein the NKG2 member is NKG2A.

### Claim 21 (depends on 17)

The method of claim 17, wherein the NKG2 member is NKG2C.

### Claim 22 (depends on 17)

The method of claim 17, wherein the test compound is an antibody.
