Variable regions for NKp46 binding proteins

Patent metadata

Field	Value
Publication number	US-11001629-B2
Application number	US-201616066688-A
Country	US
Kind code	B2
Filing date	Dec 20, 2016
Priority date	Dec 28, 2015
Publication date	May 11, 2021
Grant date	May 11, 2021

Abstract

NKp-46-binding immunoglobulin variable regions, and proteins such as antibodies and multispecific proteins that comprise the variable regions are provided. The proteins can bind and specifically redirect NK cells to lyse a target cell of interest. The proteins have utility in the treatment of disease, notably cancer or infectious disease.

First claim

The invention claimed is:

1. A protein or polypeptide comprising an antigen binding domain that binds a human NKp46 polypeptide, wherein the domain comprises a heavy chain variable region (VH) and a light chain variable region (VL) combination selected from the group consisting of:
(a) a VH comprising an amino acid sequence of SEQ ID NOS: 199 or 200 (NKp46-1 H1 or H3 variable domain), and a VL comprising an amino acid sequence of the amino acid sequence of SEQ ID NO: 201 (NKp46-1 L1 variable domain);
(b) a VH comprising an amino acid sequence of SEQ ID NOS: 202, 203 or 204 (NKp46-2 H1, H2 or H3 variable domain), and a VL comprising an amino acid sequence of SEQ ID NO: 205 (NKp46-2 L1 variable domain);
(c) a VH comprising an amino acid sequence of SEQ ID NOS: 206, 207 or 208 (NKp46-3 H1, H3 or H4 variable domain), and a VL comprising an amino acid sequence of SEQ ID NO: 209 (NKp46-3 L1 variable domain);
(d) a VH comprising an amino acid sequence of SEQ ID NOS: 210, 211 or 212 (NKp46-4 H1 variable domain), and a VL comprising an amino acid sequence of SEQ ID NO: 213 (NKp46-4 L2 variable domain);
(e) a VH comprising an amino acid sequence of SEQ ID NO: 215 (NKp46-9 H2 variable domain), and a VL comprising an amino acid sequence of SEQ ID NOS: 217 or 218 (NKp46-9 L1 or L2 variable domain); or
(f) a VH comprising an amino acid sequence of SEQ ID NO: 216 (NKp46-9 H3 variable domain), and a VL comprising an amino acid sequence of SEQ ID NOS: 217 or 218 (NKp46-9 L1 or L2 variable domain).

2. The protein or polypeptide of claim 1 , wherein the protein is an antibody.

3. The protein or polypeptide of claim 1 , wherein the VH and the VL are placed on a single polypeptide chain and fused to one another via a peptide linker.

4. The protein or polypeptide of claim 1 , wherein the VH is positioned on a first polypeptide chain within the protein and the VL is positioned on a second polypeptide chain within the protein.

5. The protein or polypeptide of claim 2 , wherein the protein is a full length IgG antibody, or a fragment thereof that retains binding to the NKp46 polypeptides.

6. The protein or polypeptide claim 1 , wherein the protein binds a Macaca fascicularis (cynomolgus) NKp46 polypeptide.

Assignees

• Innate Pharma

Inventors

• Gauthier Laurent
• Anceriz Nadia
• Morel Ariane
• Rossi Benjamin

Classifications

• A61P37/06

  Immunosuppressants, e.g. drugs for graft rejection · CPC title

• C07K16/2887

  against CD20 · CPC title

• A61P29/00

  Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] · CPC title

• C07K2317/92

  Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value · CPC title

• C07K2317/34

  Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues · CPC title