Anti-pd1 antibodies and their use as therapeutics and diagnostics

Patent metadata

Field	Value
Publication number	US-2018251551-A1
Application number	US-201815978695-A
Country	US
Kind code	A1
Filing date	May 14, 2018
Priority date	Sep 13, 2013
Publication date	Sep 6, 2018
Grant date	—

Abstract

Provided are antibodies that specifically bind to Programmed Death-1 (PD1, Pdcd-1, or CD279) and inhibit PD1-mediated cellular signaling and activities in immune cells, antibodies binding to a set of amino acid residues required for its ligand binding, and uses of these antibodies to treat or diagnose cancer, infectious diseases or other pathological disorders modulated by PD1-mediated functions.

First claim

What is claims is:

1 . A monoclonal antibody which binds human PD-1, comprising,
a PD-1 binding domain, and an IgG4 Fc region comprising an amino acid mutation at position 228 and at least one additional amino acid mutation; wherein the at least one additional mutation causes the antibody to exhibit reduced binding to at least one Fcγ receptor relative to Fc binding of a reference IgG4 antibody having a mutation at position 228 and no other Fc region mutation; and wherein the numbering of the residues in the IgG4 Fc region is that of the EU numbering system.

2 . The antibody of claim 1 , wherein the mutation at position 228 is S228P.

3 . The antibody of claim 1 , wherein the IgG4 region comprises amino acid mutations at positions 228, 234, and 235

4 . The antibody of claim 3 , wherein the mutation at position 234 is F234V.

5 . The antibody of claim 3 , wherein the mutation at position 235 is L235A.

6 . The antibody of claim 1 , wherein the IgG4 Fc region comprises amino acid mutations of S228P, F234V, and L235A.

7 . The antibody of claim 1 , wherein the at least one Fcγ receptor is selected from FcγRI, FcγRIIA, FcγRIIB, and FcγRIIIA.

8 . The antibody of claim 1 , wherein the antibody exhibits reduced effector function relative to the reference IgG4 antibody.

9 . The antibody of claim 8 , wherein the reduced effector function is antibody-dependent cell-mediated cytotoxicity (ADCC).

10 . The antibody of claim 1 , wherein the antibody exhibits anti-tumor activity.

11 . The antibody of claim 1 , wherein the antibody suppresses PD-1 mediated signal transduction.

Assignees

• Beigene Ltd

Inventors

• Li Kang
• Zhang Tong
• Song Jing
• Xu Lanlan
• Liu Qi
• Peng Hao

Classifications

• A61P35/00

  Antineoplastic agents · CPC title

• C07K2317/92

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

• C07K2317/567

  Framework region [FR] · CPC title

• C07K2317/55

  Fab or Fab' · CPC title

• C07K2317/70

  characterized by effect upon binding to a cell or to an antigen · CPC title