NKp46 binding proteins

• US 10,519,234 B2
• Filed: 06/23/2015
• Issued: 12/31/2019
• Est. Priority Date: 06/27/2014
• Status: Active Grant

• Current Assignee: Innate Pharma
• Original Assignee: Innate Pharma
• Inventors: Gauthier, Laurent, Anceriz, Nadia, Morel, Ariane, Rossi, Benjamin
• Primary Examiner(s): Huynh, Phuong
• Application Number:
  US15/321,650
• Publication Number:
  US 20170198038A1
• Time in Patent Office: 1,652 Days
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 37/02 Immunomodulators
• CPC Class Codes: C07K 16/2803 against the immunoglobulin superfamily
• CPC Class Codes: C07K 16/2866 against receptors for cytokines, lymphokines, interferons
• CPC Class Codes: C07K 2317/31 multispecific
• CPC Class Codes: C07K 2317/71 Decreased effector function due to an Fc-modification
• CPC Class Codes: C07K 2317/92 Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
• CPC Class Codes: C07K 2319/30 Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto

Abstract

Multispecific proteins that bind and specifically redirect NK cells to lyse a target cell of interest are provided without non-specific activation of NK cells in absence of target cells. The proteins have utility in the treatment of disease, notably cancer or infectious disease.

Claims

1. A recombinant monoclonal antibody or antigen-binding antibody fragment that specifically binds NKp46 comprising:

(a) a heavy chain variable region comprising CDRs 1, 2, and 3 of the heavy chain variable region of SEQ ID NO;

3 and a light chain variable region comprising CDRs 1, 2, and 3 of the light chain variable region of SEQ ID NO;

4;

(b) a heavy chain variable region comprising CDRs 1, 2 and 3 of the heavy chain variable region of SEQ ID NO;

5 and a light chain variable region comprising CDRs 1, 2, and 3 of the light chain variable region of SEQ ID NO;

6;

(c) a heavy chain variable region comprising CDRs 1, 2, and 3 of the heavy chain variable region of SEQ ID NO;

7 and a light chain variable region comprising CDRs 1, 2, and 3 of the light chain variable region of SEQ ID NO;

8;

(d) a heavy chain variable region comprising CDRs 1, 2, and 3 of the heavy chain variable region of SEQ ID NO;

9 and a light chain variable region comprising CDRs 1, 2, and 3 of the light chain variable region of SEQ ID NO;

10;

(e) a heavy chain variable region comprising CDRs 1, 2, and 3 of the heavy chain variable region of SEQ ID NO;

11 and a light chain variable region comprising CDRs 1, 2, and 3 of the light chain variable region of SEQ ID NO;

12;

or

(f) a heavy chain variable region comprising CDRs 1, 2, and 3 of the heavy chain variable region of SEQ ID NO;

13 and a light chain variable region comprising CDRs 1, 2, and 3 of the light chain variable region of SEQ ID NO;

14.

2. A pharmaceutical composition comprising an antibody or antigen-binding antibody fragment according to claim 1, and a pharmaceutically acceptable carrier.

3. The antibody of claim 1, wherein the antibody or antibody fragment comprises a heavy chain variable region comprising CDRs 1, 2, and 3 of the heavy chain variable region of SEQ ID NO:

3 and a light chain variable region comprising CDRs 1, 2, and 3 of the light chain variable region of SEQ ID NO;

4.

4. The antibody of claim 1, wherein the antibody or antibody fragment comprises a heavy chain variable region comprising CDRs 1, 2, and 3 of the heavy chain variable region of SEQ ID NO:

5 and a light chain variable region comprising CDRs 1, 2, and 3 of the light chain variable region of SEQ ID NO;

6.

5. The antibody of claim 1, wherein the antibody or antibody fragment comprises a heavy chain variable region comprising CDRs 1, 2, and 3 of the heavy chain variable region of SEQ ID NO:

7 and a light chain variable region comprising CDRs 1, 2, and 3 of the light chain variable region of SEQ ID NO;

8.

6. The antibody of claim 1, wherein the antibody or antibody fragment comprises a heavy chain variable region comprising CDRs 1, 2, and 3 of the heavy chain variable region of SEQ ID NO:

9 and a light chain variable region comprising CDRs 1, 2, and 3 of the light chain variable region of SEQ ID NO;

10.

7. The antibody of claim 1, wherein the antibody or antibody fragment comprises a heavy chain variable region comprising CDRs 1, 2, and 3 of the heavy chain variable region of SEQ ID NO:

11 and a light chain variable region comprising CDRs 1, 2, and 3 of the light chain variable region of SEQ ID NO;

12.

8. The antibody of claim 1, wherein the antibody or antibody fragment comprises a heavy chain variable region comprising CDRs 1, 2, and 3 of the heavy chain variable region of SEQ ID NO:

13 and a light chain variable region comprising CDRs 1, 2, and 3 of the light chain variable region of SEQ ID NO;

14.

9. The antibody of claim 1, wherein the antibody or antibody fragment is a monospecific antibody.

10. A multispecific protein comprising any one of the antibody fragment of claim 1.

11. A bispecific protein comprising any one of the antibody fragment of claim 1.

12. A recombinant nucleic acid encoding an antibody or antigen-binding antibody fragment that specifically binds NKp46 comprising:

(a) a heavy chain variable region comprising CDRs 1, 2, and 3 of the heavy chain variable region of SEQ ID NO;

3 and a light chain variable region comprising CDRs 1, 2, and 3 of the light chain variable region of SEQ ID NO;

4;

(b) a heavy chain variable region comprising CDRs 1, 2, and 3 of the heavy chain variable region of SEQ ID NO;

5 and a light chain variable region comprising CDRs 1, 2, and 3 of the light chain variable region of SEQ ID NO;

6;

(c) a heavy chain variable region comprising CDRs 1, 2, and 3 of the heavy chain variable region of SEQ ID NO;

7 and a light chain variable region comprising CDRs 1, 2, and 3 of the light chain variable region of SEQ ID NO;

8;

(d) a heavy chain variable region comprising CDRs 1, 2, and 3 of the heavy chain variable region of SEQ ID NO;

9 and a light chain variable region comprising CDRs 1, 2, and 3 of the light chain variable region of SEQ ID NO;

10;

(e) a heavy chain variable region comprising CDRs 1, 2, and 3 of the heavy chain variable region of SEQ ID NO;

11 and a light chain variable region comprising CDRs 1, 2, and 3 of the light chain variable region of SEQ ID NO;

12;

or

(f) a heavy chain variable region comprising CDRs 1, 2, and 3 of the heavy chain variable region of SEQ ID NO;

13 and a light chain variable region comprising CDRs 1, 2, and 3 of the light chain variable region of SEQ ID NO;

14.