# US 11,078,275 B2 · Compound that specifically binds to KIR3DL2 for use in the treatment of peripheral T cell lymphoma

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- Number: US 11,078,275 B2
- Document ID: US11078275B2
- Status: Granted
- Kind: B2
- Application number: 16/240,906
- Filed: 2019-01-07
- Published: 2019-05-02
- Granted: 2021-08-03
- Earliest claimed: 2013-02-20
- Assignees: Innate Pharma
- Applicants: Innate Pharma
- Inventors: Cecile Bonnafous; Helene Sicard; Renaud Buffet
- Web page: https://patentgrep.com/patent/US11078275B2

## CPC

- C07K 16/2803: {against the immunoglobulin superfamily}
- A61P 35/00: Antineoplastic agents
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C07K 16/3023: {Lung}
- C07K 16/3061: {Blood cells}
- G01N 33/57505: of the blood, e.g. leukaemia
- A61K 2039/505: {comprising antibodies}
- C07K 2317/33: Crossreactivity, e.g. for species or epitope, or lack of said crossreactivity
- C07K 2317/34: Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues
- C07K 2317/732: Antibody-dependent cellular cytotoxicity [ADCC]
- G01N 2333/705: Assays involving receptors, cell surface antigens or cell surface determinants
- G01N 2333/70503: Immunoglobulin superfamily, e.g. VCAMs, PECAM, LFA-3
- 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)
- 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)

## Abstract

The present invention relates to methods for the treatment, prevention and diagnosis of peripheral T cell lymphoma using compounds that specifically bind KIR3DL2. The invention also relates to use of antibodies that specifically bind KIR3DL2 in diagnostic and theranostic assays in the detection and treatment of peripheral T cell lymphoma.

## Claims

### Claim 1

A method of treating an enteropathy-associated T cell lymphoma (EATL), comprising administering to an individual suffering from said EATL a therapeutically active amount of an antibody that binds a KIR3DL2 polypeptide comprising the amino acid sequence of SEQ ID NO: 1 and that further: i) directs ADCC toward a KIR3DL2-expressing cell, or ii) delivers a cytotoxic agent to a KIR3DL2-expressing cell.

### Claim 2 (depends on 1)

The method of claim 1, wherein the treatment comprises:
a) determining the KIR3DL2 polypeptide status of malignant cells within the individual having an EATL, and
b) upon a determination that the individual has KIR3DL2 polypeptide expressed on the surface of malignant cells, administering to the individual said antibody that binds a KIR3DL2 polypeptide comprising the amino acid sequence of SEQ ID NO: 1 and that further: i) directs ADCC toward the KIR3DL2-expressing malignant cells and/or ii) delivers a cytotoxic agent to the KIR3DL2-expressing malignant cells.

### Claim 3 (depends on 1)

The method of claim 1, wherein the anti-KIR3DL2 antibody directs ADCC toward a KIR3DL2-expressing cell.

### Claim 4 (depends on 3)

The method of claim 3, wherein the antibody comprises an amino acid modification that enhances binding to a human Fcγ receptor.

### Claim 5 (depends on 3)

The method of claim 3, wherein the anti-KIR3DL2 antibody binds human KIR3DL2 but does not bind to human KIR3DL1.

### Claim 6 (depends on 1)

The method of claim 1, wherein the antibody is linked to a cytotoxic agent.

### Claim 7 (depends on 1)

The method of claim 1, wherein the anti-KIR3DL2 antibody binds human KIR3DL2 but does not bind to human KIR3DL1.

### Claim 8 (depends on 1)

The method of claim 1, wherein the KIR3DL2 antibody comprises an antibody variable region comprising:
a) a heavy chain variable region comprising a heavy chain CDR1 (hCDR1) comprising SEQ ID NO: 9, a heavy chain CDR2 (hCDR2) comprising SEQ ID NO: 10 or 11, a heavy chain CDR3 (hCDR3) comprising SEQ ID NO: 12 and a variable region light chain comprising a light chain CDR1 (LCDR1) comprising SEQ ID NO: 13, a light chain CDR2 (LCDR2) comprising SEQ ID NO: 14, and a light chain CDR3 (LCDR3) comprising SEQ ID NO:15;
b) a heavy chain variable region comprising a heavy chain CDR1 (hCDR1) comprising SEQ ID NO: 18, 19 or 20, a heavy chain CDR2 (hCDR2) comprising SEQ ID NO: 21 or 22, a heavy chain CDR3 (hCDR3) comprising SEQ ID NO: 23 and a variable region light chain comprising a light chain CDR1 (LCDR1) comprising SEQ ID NO: 24, a light chain CDR2 (LCDR2) comprising SEQ ID NO: 25, and a light chain CDR3 (LCDR3) comprising SEQ ID NO:26;
c) a heavy chain variable region comprising a heavy chain CDR1 (hCDR1) comprising SEQ ID NO: 37, a heavy chain CDR2 (hCDR2) comprising SEQ ID NO: 38, a heavy chain CDR3 (hCDR3) comprising SEQ ID NO: 39 and a variable region light chain comprising a light chain CDR1 (LCDR1) comprising SEQ ID NO: 40, a light chain CDR2 (LCDR2) comprising SEQ ID NO: 41, and a light chain CDR3 (LCDR3) comprising SEQ ID NO: 42; or
d) a heavy chain variable region comprising a heavy chain CDR1 (hCDR1) comprising SEQ ID NO: 34, a heavy chain CDR2 (hCDR2) comprising SEQ ID NO: 35, a heavy chain CDR3 (hCDR3) comprising SEQ ID NO: 36 and a variable region light chain comprising a light chain CDR1 (LCDR1) comprising SEQ ID NO: 40, a light chain CDR2 (LCDR2) comprising SEQ ID NO: 41, and a light chain CDR3 (LCDR3) comprising SEQ ID NO: 42.

### Claim 9 (depends on 8)

The method of claim 8, wherein the KIR3DL2 antibody comprises an antibody variable region comprising a heavy chain variable region comprising a heavy chain CDR1 (hCDR1) comprising SEQ ID NO: 9, a heavy chain CDR2 (hCDR2) comprising SEQ ID NO: 10 or 11, a heavy chain CDR3 (hCDR3) comprising SEQ ID NO: 12 and a variable region light chain comprising a light chain CDR1 (LCDR1) comprising SEQ ID NO: 13, a light chain CDR2 (LCDR2) comprising SEQ ID NO: 14, and a light chain CDR3 (LCDR3) comprising SEQ ID NO: 15.

### Claim 10 (depends on 8)

The method of claim 8, wherein the KIR3DL2 antibody comprises an antibody variable region comprising a heavy chain variable region comprising a heavy chain CDR1 (hCDR1) comprising SEQ ID NO: 18, 19 or 20, a heavy chain CDR2 (hCDR2) comprising SEQ ID NO: 21 or 22, a heavy chain CDR3 (hCDR3) comprising SEQ ID NO: 23 and a variable region light chain comprising a light chain CDR1 (LCDR1) comprising SEQ ID NO: 24, a light chain CDR2 (LCDR2) comprising SEQ ID NO: 25, and a light chain CDR3 (LCDR3) comprising SEQ ID NO: 26.

### Claim 11 (depends on 8)

The method of claim 8, wherein the KIR3DL2 antibody comprises an antibody variable region comprising a heavy chain variable region comprising a heavy chain CDR1 (hCDR1) comprising SEQ ID NO: 37, a heavy chain CDR2 (hCDR2) comprising SEQ ID NO: 38, a heavy chain CDR3 (hCDR3) comprising SEQ ID NO: 39 and a variable region light chain comprising a light chain CDR1 (LCDR1) comprising SEQ ID NO: 40, a light chain CDR2 (LCDR2) comprising SEQ ID NO: 41, and a light chain CDR3 (LCDR3) comprising SEQ ID NO: 42.

### Claim 12 (depends on 8)

The method of claim 8, wherein the KIR3DL2 antibody comprises an antibody variable region comprising a heavy chain variable region comprising a heavy chain CDR1 (hCDR1) comprising SEQ ID NO: 34, a heavy chain CDR2 (hCDR2) comprising SEQ ID NO: 35, a heavy chain CDR3 (hCDR3) comprising SEQ ID NO: 36 and a variable region light chain comprising a light chain CDR1 (LCDR1) comprising SEQ ID NO: 40, a light chain CDR2 (LCDR2) comprising SEQ ID NO: 41, and a light chain CDR3 (LCDR3) comprising SEQ ID NO:42.