Methods of treating immune disorders using pd-1 binding proteins

Patent metadata

Field	Value
Publication number	US-2021069325-A1
Application number	US-202016945706-A
Country	US
Kind code	A1
Filing date	Jul 31, 2020
Priority date	Sep 19, 2016
Publication date	Mar 11, 2021
Grant date	—

Abstract

Provided herein are methods for managing, treating, or preventing immune disorders, such as autoimmune diseases, using proteins that specifically bind to Programmed Death-1 (PD-1) and modulate the expression and/or activity of PD-1.

First claim

1 .- 108 . (canceled)

109 . A method of managing, preventing, or treating an immune disorder in a subject, comprising administering to the subject a therapeutically effective amount of an antibody or antigen-binding fragment thereof that
(A) (a) binds to an epitope of human PD-1 recognized by an antibody comprising a light chain variable region having an amino acid sequence of SEQ ID NO:8 and a heavy chain variable region having an amino acid sequence of SEQ ID NO:13; or
(b) competes for the binding to human PD-1 with an antibody comprising a light chain variable region having an amino acid sequence of SEQ ID NO:8 and a heavy chain variable region having an amino acid sequence of SEQ ID NO:13; or
(B) binds to PD-1, wherein the antibody or antigen-binding fragment thereof comprises:
(a) a light chain variable region (VL) comprising VL complementarity determining region 1 (CDR1), VL CDR2, and VL CDR3 of any one of antibodies PD1AB-1, PD1AB-2, PD1AB-3, PD1AB-4, PD1AB-5, or PD1AB-6 as set forth in Table 1; and/or
(b) a heavy chain variable region (VH) comprising VH complementarity determining region 1 (CDR1), VH CDR2, and VH CDR3 of any one of antibodies PD1AB-1, PD1AB-2, PD1AB-3, PD1AB-4, PD1AB-5, or PD1AB-6 as set forth in Table 2.

110 . The method of claim 109 , wherein
(i) the antibody or antigen-binding fragment thereof comprises:
(a) a light chain variable region (VL) further comprising VL framework 1 (FR1), VL FR2, VL FR3, and VL FR4 of any one of antibodies PD1AB-1, PD1AB-2, PD1AB-3, PD1AB-4, PD1AB-5, or PD1AB-6 as set forth in Table 3; and/or
(b) a heavy chain variable region (VH) further comprising VH framework 1 (FR1), VH FR2, VH FR3, and VH FR4 of any one of antibodies PD1AB-1, PD1AB-2, PD1AB-3, PD1AB-4, PD1AB-5, or PD1AB-6 as set forth in Table 4;
(ii) the VL CDR1, VL CDR2, and VL CDR3 that comprise amino acid sequences of SEQ ID NOS:1, 2, and 3, respectively, and the VH CDR1, VH CDR2, and VH CDR3 comprise amino acid sequences of SEQ ID NOS:4, 5, and 6, respectively; (iii) the VL CDR1, VL CDR2, and VL CDR3 that comprise amino acid sequences of SEQ ID NOS:7, 2, and 3, respectively, and the VH CDR1, VH CDR2, and VH CDR3 comprise amino acid sequences of SEQ ID NOS:4, 5, and 6, respectively; (iv) the antibody or antigen-binding fragment thereof comprises a VL comprising an amino acid sequence of SEQ ID NO:8, SEQ ID NO:9 or SEQ ID NO:10; (v) the antibody or antigen-binding fragment thereof comprises a VH comprising an amino acid sequence of SEQ ID NO:11, SEQ ID NO:12 or SEQ ID NO:13; (vi) the antibody or antigen-binding fragment thereof comprises:
(a) a VL comprising an amino acid sequence of SEQ ID NO:8; and
(b) a VH comprising an amino acid sequence of SEQ ID NO:11;
(vii) the antibody or antigen-binding fragment thereof comprises:
(a) a VL comprising an amino acid sequence of SEQ ID NO:9; and
(b) a VH comprising an amino acid sequence of SEQ ID NO:11;
(viii) the antibody or antigen-binding fragment thereof comprises:
(a) a VL comprising an amino acid sequence of SEQ ID NO:10; and
(b) a VH comprising an amino acid sequence of SEQ ID NO:11;
(ix) the antibody or antigen-binding fragment thereof comprises:
(a) a VL comprising an amino acid sequence of SEQ ID NO:8; and
(b) a VH comprising an amino acid sequence of SEQ ID NO:12;
(x) the antibody or antigen-binding fragment thereof comprises:
(a) a VL comprising an amino acid sequence of SEQ ID NO:9; and
(b) a VH comprising an amino acid sequence of SEQ ID NO:12;
(xi) the antibody or antigen-binding fragment thereof comprises:
(a) a VL comprising an amino acid sequence of SEQ ID NO:10; and
(b) a VH comprising an amino acid sequence of SEQ ID NO:12;
(xii) the antibody or antigen-binding fragment thereof comprises:
(a) a VL comprising an amino acid sequence of SEQ ID NO:8; and
(b) a VH comprising an amino acid sequence of SEQ ID NO:13;
(xiii) the antibody or antigen-binding fragment thereof comprises:
(a) a VL comprising an amino acid sequence of SEQ ID NO:9; and
(b) a VH comprising an amino acid sequence of SEQ ID NO:13; or
(xiv) the antibody or antigen-binding fragment thereof comprises:
(a) a VL comprising an amino acid sequence of SEQ ID NO:10; and
(b) a VH comprising an amino acid sequence of SEQ ID NO:13.

111 . The method of claim 109 , wherein
(i) the antibody or antigen-binding fragment thereof comprises a human IgG1 Fc region or a variant thereof; (ii) the antibody or antigen-binding fragment thereof comprises a human IgG1-K322 Å Fc region; (iii) the antibody or antigen-binding fragment thereof comprises a heavy chain Fc region comprising an amino acid sequence selected from the group consisting of SEQ ID NOS:36-40;
wherein optionally the antibody or antigen-binding fragment thereof further comprises a light chain constant region comprising an amino acid sequence of SEQ ID NO:41; or
(iv) the antibody or antigen-binding fragment thereof comprises:
(a) a light chain constant region comprising an amino acid sequence of SEQ ID NO:41; and
(b) a heavy chain Fc region comprising an amino acid sequence selected from the group consisting of SEQ ID NOS:36-40.

112 . The method of claim 109 , wherein
(i) the antibody or antigen-binding fragment thereof comprises a light chain comprising an amino acid sequence of SEQ ID NO:31; (ii) the antibody or antigen-binding fragment thereof comprises a heavy chain comprising an amino acid sequence of SEQ ID NO:32; (iii) the antibody or antigen-binding fragment thereof comprises:
(a) a light chain comprising an amino acid sequence of SEQ ID NO:31; and
(b) a heavy chain comprising an amino acid sequence of SEQ ID NO:32;
(iv) wherein the antibody or antigen-binding fragment thereof comprises a heavy chain comprising an amino acid sequence of SEQ ID NO:33; (v) the antibody or antigen-binding fragment thereof comprises:
(a) a light chain comprising an amino acid sequence of SEQ ID NO:31; and
(b) a heavy chain comprising an amino acid sequence of SEQ ID NO:33;
(vi) the antibody or antigen-binding fragment thereof comprises a heavy chain comprising an amino acid sequence of SEQ ID NO:34; (vii) the antibody or antigen-binding fragment thereof comprises:
(a) a light chain comprising an amino acid sequence of SEQ ID NO:31; and
(b) a heavy chain comprising an amino acid sequence of SEQ ID NO:34;
(viii) the antibody or antigen-binding fragment thereof comprises a heavy chain comprising an amino acid sequence of SEQ ID NO:35; or (ix) the antibody or antigen-binding fragment thereof comprises:
(a) a light chain comprising an amino acid sequence of SEQ ID NO:31; and
(b) a heavy chain comprising an amino acid sequence of SEQ ID NO:35.

113 . The method of claim 109 , wherein, when bound to PD-1, the antibody or antigen-binding fragment binds to
(i) at least one of residues 100-109 within an amino acid sequence of SEQ ID NO:42;
wherein optionally, when bound to PD-1, the antibody or antigen-binding fragment binds to at least one of residues 100-105 within an amino acid sequence of SEQ ID NO:42; or
(ii) at least one residue selected from the group consisting of N33, T51, S57, L100, N102, G103, R104, D105, H107, and S109 within an amino acid sequence of SEQ ID NO:42;
wherein optionally when bound to PD-1, the antibody or antigen-binding fragment binds to
(a) N33 within an amino acid sequence of SEQ ID NO:42;
(b) T51 within an amino acid sequence of SEQ ID NO:42;
(c) S57 within an amino acid sequence of SEQ ID NO:42;
(d) L100 within an amino acid sequence of SEQ ID NO:42;
(e) N102 within an amino acid sequence of SEQ ID NO:42;
(f) G103 within an amino acid sequence of SEQ ID NO:42;
(g) R104 within an amino acid sequence of SEQ ID NO:42;
(h) D105 within an amino acid sequence of SEQ ID NO:42;
(i) H107 with

Assignees

• Celgene Corp

Inventors

• Chan Henry H
• Hur Eun Mi
• Khattri Roli
• Leung Monica
• Ringheim Garth E
• Schafer Peter H

Classifications

• A61P37/02 Primary

  Immunomodulators · CPC title

• A61K2039/505

  comprising antibodies · CPC title

• C07K2317/24

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

• C07K2317/76

  Antagonist effect on antigen, e.g. neutralization or inhibition of binding · CPC title

• C07K2317/732

  Antibody-dependent cellular cytotoxicity [ADCC] · CPC title