SIRP-Alpha BINDING PROTEINS AND METHODS OF USE THEREOF

Patent metadata

Field	Value
Publication number	US-2020102387-A1
Application number	US-201916582813-A
Country	US
Kind code	A1
Filing date	Sep 25, 2019
Priority date	Sep 27, 2018
Publication date	Apr 2, 2020
Grant date	—

Abstract

Provided herein are compositions, methods and uses involving antibodies that specifically bind to signal regulatory protein-α (SIRPα) and modulate the activity of SIRPα.

First claim

1 - 205 . (canceled)

206 . An antibody or antigen-binding fragment thereof that
(i) binds to an epitope of human SIRPα recognized by an antibody comprising a light chain variable region (VL) having an amino acid sequence of SEQ ID NO:67 and a heavy chain variable region (VH) having an amino acid sequence of SEQ ID NO:80; (ii) competes for the binding to human SIRPα with an antibody comprising a VL having an amino acid sequence of SEQ ID NO:67 and a VH having an amino acid sequence of SEQ ID NO:80; or (iii) binds to human SIRPα, wherein the antibody or antigen-binding fragment thereof comprises:
(a) a VL comprising VL complementarity determining region 1 (CDR1), VL CDR2, and VL CDR3 of any one of antibodies SIRPAB-11, SIRPAB-12, SIRPAB-1, SIRPAB-2, SIRPAB-3, SIRPAB-4, SIRPAB-5, SIRPAB-6, SIRPAB-7, SIRPAB-8, SIRPAB-9, SIRPAB-10, or SIRPAB-13 as set forth in Table 1; and/or
(b) VH complementarity determining region 1 (CDR1), VH CDR2, and VH CDR3 of any one of antibodies SIRPAB-11, SIRPAB-12, SIRPAB-1, SIRPAB-2, SIRPAB-3, SIRPAB-4, SIRPAB-5, SIRPAB-6, SIRPAB-7, SIRPAB-8, SIRPAB-9, SIRPAB-10, or SIRPAB-13 as set forth in Table 2;
wherein optionally
(1) the VL further comprising VL framework 1 (FR1), VL FR2, VL FR3, and VL FR4 of any one of antibodies SIRPAB-11, SIRPAB-12, SIRPAB-1, SIRPAB-2, SIRPAB-3, SIRPAB-4, SIRPAB-5, SIRPAB-6, SIRPAB-7, SIRPAB-8, SIRPAB-9, SIRPAB-10, or SIRPAB-13 as set forth in Table 3; and/or
(2) the VH further comprising VH framework 1 (FR1), VH FR2, VH FR3, and VH FR4 of any one of antibodies SIRPAB-11, SIRPAB-12, SIRPAB-1, SIRPAB-2, SIRPAB-3, SIRPAB-4, SIRPAB-5, SIRPAB-6, SIRPAB-7, SIRPAB-8, SIRPAB-9, SIRPAB-10, or SIRPAB-13 as set forth in Table 4.

207 . The antibody or antigen-binding fragment thereof of claim 206 (iii),
(i) wherein the VL CDR1, VL CDR2, and VL CDR3 comprise amino acid sequences of SEQ ID NOS:62, 63, and 65, respectively, and the VH CDR1, VH CDR2, and VH CDR3 comprise amino acid sequences of SEQ ID NOS:78, 69, and 57, respectively; or
(ii) wherein the VL CDR1, VL CDR2, and VL CDR3 comprise amino acid sequences of SEQ ID NOS:62, 63, and 65, respectively, and the VH CDR1, VH CDR2, and VH CDR3 comprise amino acid sequences of SEQ ID NOS:82, 83, and 57, respectively.

208 . The antibody or antigen-binding fragment thereof of claim 206 , wherein the antibody or antigen-binding fragment thereof comprises
(i) a VL comprising an amino acid sequence of SEQ ID NO:18; (ii) a VL comprising an amino acid sequence of SEQ ID NO:46; (iii) a VL comprising an amino acid sequence of SEQ ID NO:67; (iv) a VH comprising an amino acid sequence of SEQ ID NO:9; (v) a VH comprising an amino acid sequence of SEQ ID NO:22; (vi) a VH comprising an amino acid sequence of SEQ ID NO:27; (vii) a VH comprising an amino acid sequence of SEQ ID NO:32; (viii) a VH comprising an amino acid sequence of SEQ ID NO:36; (ix) a VH comprising an amino acid sequence of SEQ ID NO:42; (x) a VH comprising an amino acid sequence of SEQ ID NO:50; (xi) a VH comprising an amino acid sequence of SEQ ID NO:60; (xii) a VH comprising an amino acid sequence of SEQ ID NO:71; (xiii) a VH comprising an amino acid sequence of SEQ ID NO:76; (xiv) a VH comprising an amino acid sequence of SEQ ID NO:80; (xv) a VH comprising an amino acid sequence of SEQ ID NO:85; (xvi) a VH comprising an amino acid sequence of SEQ ID NO:90; (xvii) (a) a VL comprising an amino acid sequence of SEQ ID NO: 18; and
(b) a VH comprising an amino acid sequence of SEQ ID NO:9;
(xviii) (a) a VL comprising an amino acid sequence of SEQ ID NO: 18; and
(b) a VH comprising an amino acid sequence of SEQ ID NO:22;
(xix) (a) a VL comprising an amino acid sequence of SEQ ID NO: 18; and
(b) a VH comprising an amino acid sequence of SEQ ID NO:27;
(xx) (a) a VL comprising an amino acid sequence of SEQ ID NO: 18; and
(b) a VH comprising an amino acid sequence of SEQ ID NO:32;
(xxi) (a) a VL comprising an amino acid sequence of SEQ ID NO: 18; and
(b) a VH comprising an amino acid sequence of SEQ ID NO:36;
(xxii) (a) a VL comprising an amino acid sequence of SEQ ID NO:46; and
(b) a VH comprising an amino acid sequence of SEQ ID NO:42;
(xxiii) (a) a VL comprising an amino acid sequence of SEQ ID NO:46; and
(b) a VH comprising an amino acid sequence of SEQ ID NO:50;
(xxiv) (a) a VL comprising an amino acid sequence of SEQ ID NO:67; and
(b) a VH comprising an amino acid sequence of SEQ ID NO:60; or
(xxv) (a) a VL comprising an amino acid sequence of SEQ ID NO:67; and
(b) a VH comprising an amino acid sequence of SEQ ID NO:71;
(xxvi) (a) a VL comprising an amino acid sequence of SEQ ID NO:67; and
(b) a VH comprising an amino acid sequence of SEQ ID NO:76;
(xxvii) (a) a VL comprising an amino acid sequence of SEQ ID NO:67; and
(b) a VH comprising an amino acid sequence of SEQ ID NO:80;
(xxviii)(a) a VL comprising an amino acid sequence of SEQ ID NO:67; and
(b) a VH comprising an amino acid sequence of SEQ ID NO:85;
(xxix) (a) a VL comprising an amino acid sequence of SEQ ID NO:67; and
(b) a VH comprising an amino acid sequence of SEQ ID NO:90; or
(xxx) (a) a VL comprising an amino acid sequence selected from the group consisting of SEQ ID NOS:18, 46, and 67; and
(b) a VH comprising an amino acid sequence selected from the group consisting of SEQ ID NOS:9, 22, 27, 32, 36, 42, 50, 60, 71, 76, 80, 85, and 90.

209 . The antibody or antigen-binding fragment thereof of claim 206 , wherein the antibody or antigen-binding fragment thereof comprises
(i) a human IgG1 Fc region or a mutant thereof; (ii) a human IgG1-K322A Fc region; (iii) a human IgG1-AAS Fc region; (iv) a human IgG4 Fc region or a mutant thereof; (v) a human IgG4P Fc region; (vi) a human IgG4PE Fc region; (vii) a heavy chain Fc region comprising an amino acid sequence selected from the group consisting of SEQ ID NOS:144 and 155-159; (viii) a light chain constant region comprising an amino acid sequence of SEQ ID NO:211; (ix) (a) a light chain constant region comprising an amino acid sequence of SEQ ID NO:211; and
(b) a heavy chain Fc region comprising an amino acid sequence selected from the group consisting of SEQ ID NOS: 144 and 155-159;
(x) a light chain comprising an amino acid sequence of SEQ ID NO:143; (xi) a light chain comprising an amino acid sequence of SEQ ID NO:200; (xii) a light chain comprising an amino acid sequence of SEQ ID NO:202; (xiii) a light chain comprising an amino acid sequence of SEQ ID NO:208; (xiv) a light chain comprising an amino acid sequence of SEQ ID NO:209; (xv) a light chain comprising an amino acid sequence of SEQ ID NO:210; (xvi) a heavy chain comprising an amino acid sequence of SEQ ID NO: 142; (xvii) a heavy chain comprising an amino acid sequence of SEQ ID NO: 119; (xviii) a heavy chain comprising an amino acid sequence of SEQ ID NO:204; (xix) a heavy chain comprising an amino acid sequence of SEQ ID NO:205; (xx) a heavy chain comprising an amino acid sequence of SEQ ID NO:98; (xxi) a heavy chain comprising an amino acid sequence of SEQ ID NO: 120; (xxii) a heavy chain comprising an amino acid sequence of SEQ ID NO: 112; (xxiii) a heavy chain comprising an amino acid sequence of SEQ ID NO: 106; (xxiv) a heavy chain comprising an amino acid sequence of SEQ ID NO: 118; (xxv) a heavy chain comprising an amino acid sequence of SEQ ID NO: 111; (xxvi) a heavy chain comprising an amino acid sequence of SEQ ID NO:212; (xxvii) a heavy chain comprising an amino acid sequence of SEQ ID NO:213; (xxviii) a heavy chain comprising an amino acid sequence of SEQ ID NO:214; (xxix) a heavy chain comprising an amino acid sequence of SEQ ID NO:215; (xxx) a heavy chain comprising an amino acid sequence of SEQ ID NO:216; (xxxi) a heavy chain comprising an amino acid

Assignees

• Celgene Corp

Inventors

• Abbasian Mahan
• Chan Henry H
• Escoubet Laure
• Fenalti Gustavo
• Hariharan Kandasamy
• Leung Monica Wai Ling
• Mavrommatis Konstantinos
• Mikolon David P
• Raymon Heather K
• Santos Carlo Steven
• Sun Jeonghoon
• Trout Christina Valerie

Classifications

• C07K2317/76

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

• C07K2317/734

  Complement-dependent cytotoxicity [CDC] · CPC title

• C07K16/2887

  against CD20 · CPC title

• A61K2039/507

  Comprising a combination of two or more separate antibodies · CPC title

• C07K2317/21

  from primates, e.g. man · CPC title