Methods and compositions relating to anti-PD1 antibody reagents

Patent metadata

Field	Value
Publication number	US-12559557-B2
Application number	US-202217870010-A
Country	US
Kind code	B2
Filing date	Jul 21, 2022
Priority date	May 1, 2017
Publication date	Feb 24, 2026
Grant date	Feb 24, 2026

Abstract

Described herein are novel anti-PD1 antibody reagents (e.g., antibodies, antigen-binding fragments thereof, and/or chimeric antigen receptors). Also described herein antibody-drug conjugates or kits comprising the disclosed antibody reagents, as well as methods of treating cancer by administering the disclosed antibody reagents.

First claim

What is claimed herein is:

1 . A nucleic acid sequence encoding an antibody, antibody reagent, antigen-binding fragment thereof, or chimaeric antigen receptor (CAR), that specifically binds an PD1 polypeptide, said antibody reagent, antigen-binding portion thereof, or CAR comprising:
heavy chain complementarity determining regions (CDRs) having the amino acid sequences of SEQ ID NOs: 23-25 and light chain CDRs having the amino acid sequences of SEQ ID NO: 26, DAS and SEQ ID NO: 28; or heavy chain CDRs having the amino acid sequences of SEQ ID NOs: 29-31 and light chain CDRs having the amino acid sequences of SEQ ID NO: 32, DAS and SEQ ID NO: 34; or heavy chain CDRs having the amino acid sequences of SEQ ID NOs: 35-37 and light chain CDRs having the amino acid sequences of SEQ ID NO: 38, DAS and SEQ ID NO: 40; or heavy chain CDRs having the amino acid sequences of SEQ ID NOs: 41-43 and light chain CDRs having the amino acid sequences of SEQ ID NO: 44, DAF and SEQ ID NO:46; or heavy chain CDRs having the amino acid sequences of SEQ ID NOs: 47-49 and light chain CDRs having the amino acid sequences of SEQ ID NO: 50, DAS and SEQ ID NO: 52; or heavy chain CDRs having the amino acid sequences of SEQ ID NOs: 53-55 and light chain CDRs having the amino acid sequences of SEQ ID NO: 56, GAS and SEQ ID NO: 58; or heavy chain CDRs having the amino acid sequences of SEQ ID NOs: 59-61 and light chain CDRs having the amino acid sequences of SEQ ID NO: 62, DAS and SEQ ID NO: 64; or heavy chain CDRs having the amino acid sequences of SEQ ID NOs: 65-67 and light chain CDRs having the amino acid sequences of SEQ ID NO: 68, DAS and SEQ ID NO: 70; or heavy chain CDRs having the amino acid sequences of SEQ ID NOs: 71-73 and light chain CDRs having the amino acid sequences of SEQ ID NO: 74, DAS and SEQ ID NO: 76; or heavy chain CDRs having the amino acid sequences of SEQ ID NOs: 77-79 and light chain CDRs having the amino acid sequences of SEQ ID NO: 80, DAS and SEQ ID NO: 82; or heavy chain CDRs having the amino acid sequences of SEQ ID NOs: 83-85 and light chain CDRs having the amino acid sequences of SEQ ID NO: 86, DAS and SEQ ID NO: 88.

2 . The nucleic acid of claim 1 , wherein the antibody, antibody reagent, antigen-binding portion thereof, or CAR comprises the heavy chain sequence of any of SEQ ID NOs: 1, 3, 5, 7, 9, 11, 13, 15, 17, 19 or 21.

3 . The nucleic acid of claim 1 , wherein the antibody, antibody reagent, antigen-binding portion thereof, or CAR comprises the light chain sequence of any of SEQ ID NOs: 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, or 22.

4 . The nucleic acid of claim 1 , wherein the antibody, antibody reagent, antigen-binding portion thereof, or CAR comprises:
the heavy chain sequence of SEQ ID NO: 1 and the light chain sequence of SEQ ID NO: 2; or the heavy chain sequence of SEQ ID NO: 3 and the light chain sequence of SEQ ID NO: 4; or the heavy chain sequence of SEQ ID NO: 5 and the light chain sequence of SEQ ID NO: 6; or the heavy chain sequence of SEQ ID NO: 7 and the light chain sequence of SEQ ID NO: 8; or the heavy chain sequence of SEQ ID NO: 9 and the light chain sequence of SEQ ID NO: 10; or the heavy chain sequence of SEQ ID NO: 11 and the light chain sequence of SEQ ID NO: 12; or the heavy chain sequence of SEQ ID NO: 13 and the light chain sequence of SEQ ID NO: 14; or the heavy chain sequence of SEQ ID NO: 15 and the light chain sequence of SEQ ID NO: 16; or the heavy chain sequence of SEQ ID NO: 17 and the light chain sequence of SEQ ID NO: 18; or the heavy chain sequence of SEQ ID NO: 19 and the light chain sequence of SEQ ID NO: 20; or the heavy chain sequence of SEQ ID NO: 21 and the light chain sequence of SEQ ID NO: 22.

5 . The nucleic acid of claim 1 , wherein the antibody, antibody reagent, antigen-binding portion thereof, or CAR further comprises a conservative substitution in a sequence not comprised by a CDR.

6 . The nucleic acid of claim 1 , wherein the antibody, antibody reagent, antigen-binding portion thereof, or CAR is fully human or fully humanized.

7 . The nucleic acid of claim 1 , wherein the antibody, antibody reagent, antigen-binding portion thereof, or CAR is fully humanized except for the CDR sequences.

8 . The nucleic acid of claim 1 , wherein the antibody, antibody reagent, antigen-binding portion thereof, or CAR is selected from the group consisting of:
an immunoglobulin molecule, a monoclonal antibody, a chimeric antibody, a CDR-grafted antibody, a humanized antibody, a Fab, a Fab′, a F(ab′)2, a Fv, a disulfide linked Fv, a scFv, a diabody, a multispecific antibody, a dual specific antibody, an anti-idiotypic antibody, and a bispecific antibody.

9 . A cell comprising an antibody, antibody reagent, antigen-binding fragment thereof, or chimaeric antigen receptor (CAR), that specifically binds an PD1 polypeptide, said antibody reagent, antigen-binding portion thereof, or CAR is encoded by a nucleic acid sequence of claim 1 .

10 . A solid support comprising an antibody, antibody reagent, or antigen-binding fragment thereof, that specifically binds an PD1 polypeptide, said antibody reagent, or antigen-binding portion thereof is encoded by a nucleic acid sequence of claim 1 .

11 . The solid support of claim 10 , wherein the antibody, antibody reagent or antigen-binding fragment thereof is detectably labeled.

12 . The solid support of claim 10 , wherein the solid support comprises a particle, a bead, a polymer, or a substrate.

13 . A kit for the detection of PD1 polypeptide in a sample, the kit comprising a solid support of claim 10 .

14 . The nucleic acid sequence of claim 1 , wherein the antibody reagent, antigen-binding portion thereof, or CAR comprises:
heavy chain CDRs having the amino acid sequences of SEQ ID NOs: 23-25 and light chain CDRs having the amino acid sequences of SEQ ID NO: 26, DAS and SEQ ID NO: 28; or heavy chain CDRs having the amino acid sequences of SEQ ID NOs: 29-31 and light chain CDRs having the amino acid sequences of SEQ ID NO: 32, DAS and SEQ ID NO: 34; or heavy chain CDRs having the amino acid sequences of SEQ ID NOs: 35-37 and light chain CDRs having the amino acid sequences of SEQ ID NO: 38, DAS and SEQ ID NO: 40; or heavy chain CDRs having the amino acid sequences of SEQ ID NOs: 41-43 and light chain CDRs having the amino acid sequences of SEQ ID NO: 44, DAF and SEQ ID NO:46; or heavy chain CDRs having the amino acid sequences of SEQ ID NOs: 47-49 and light chain CDRs having the amino acid sequences of SEQ ID NO: 50, DAS and SEQ ID NO: 52; or heavy chain CDRs having the amino acid sequences of SEQ ID NOs: 59-61 and light chain CDRs having the amino acid sequences of SEQ ID NO: 62, DAS and SEQ ID NO: 64; or heavy chain CDRs having the amino acid sequences of SEQ ID NOs: 65-67 and light chain CDRs having the amino acid sequences of SEQ ID NO: 68, DAS and SEQ ID NO: 70; or heavy chain CDRs having the amino acid sequences of SEQ ID NOs: 71-73 and light chain CDRs having the amino acid sequences of SEQ ID NO: 74, DAS and SEQ ID NO: 76; or heavy chain CDRs having the amino acid sequences of SEQ ID NOs: 77-79 and light chain CDRs having the amino acid sequences of SEQ ID NO: 80, DAS and SEQ ID NO: 82; or heavy chain CDRs having the amino acid sequences of SEQ ID NOs: 83-85 and light chain CDRs having the amino acid sequences of SEQ ID NO: 86, DAS and SEQ ID NO: 88.

15 . The nucleic acid sequence of claim 1 , wherein the antibody reagent, antigen-binding portion thereof, or CAR comprises heavy chain CDRs having the amino acid sequences of SEQ ID NOs: 71-73 and light chain CDRs having the ami

Assignees

• Childrens Medical Ct Corp

Inventors

• Alt Frederick W
• Tian Ming
• Cheng Hwei-Ling

Classifications

• A61K35/17

  Lymphocytes; B-cells; T-cells; Natural killer cells; Interferon-activated or cytokine-activated lymphocytes (when activated by a specific antigen A61K39/00) · CPC title

• C07K16/2803

  against the immunoglobulin superfamily · CPC title

• A61K39/001111

  Immunoglobulin superfamily · CPC title

• C07K2317/565

  Complementarity determining region [CDR] · CPC title

• C07K2317/24

  containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered · CPC title