Anti-hrs antibodies and combinaton therapies for treating cancers

Patent metadata

Field	Value
Publication number	US-2018282402-A1
Application number	US-201715828170-A
Country	US
Kind code	A1
Filing date	Nov 30, 2017
Priority date	Nov 30, 2016
Publication date	Oct 4, 2018
Grant date	—

Abstract

Provided are antibodies that specifically bind to human histidyl-tRNA synthetase and related therapeutic compositions and methods for treating cancer, including as standalone therapies or in combination with cancer immunotherapies, for example, immune checkpoint modulators such as PD-1 inhibitors.

First claim

1 . A therapeutic composition, comprising at least one antibody or antigen-binding fragment there that specifically binds to a human histidyl-tRNA synthetase (HRS) polypeptide (an anti-HRS antibody) and comprises a heavy chain variable region (V H ) sequence that comprises complementary determining region V H CDR1, V H CDR2, and V H CDR3 sequences, and a light chain variable region (V L ) sequence that comprises complementary determining region V L CDR1, V L CDR2, and V L CDR3 sequences, wherein:
the V H CDR1, V H CDR2, and V H CDR3 sequences comprise the consensus sequences of SEQ ID NOs:396, 397, and 398 (as defined in Table A3), respectively, and the V L CDR1, V L CDR2, and V L CDR3 sequences comprise the consensus sequences SEQ ID NOs: 399, 400, and 401 (as defined in Table A3), respectively, including variants thereof; the V H CDR1, V H CDR2, and V H CDR3 sequences comprise the consensus sequences of SEQ ID NOs: 402, 403, and 404 (as defined in Table A3), respectively, and the V L CDR1, V L CDR2, and V L CDR3 sequences comprise the consensus sequences of SEQ ID NOs: 405, 406, and 407 (as defined in Table A3), respectively, including variants thereof; the V H CDR1, V H CDR2, and V H CDR3 sequences comprise the consensus sequences of SEQ ID NOs: 408, 409, and 410 (as defined in Table A3), respectively, and the V L CDR1, V L CDR2, and V L CDR3 sequences comprise the consensus sequences of SEQ ID NOs: 411, 412, and 413 (as defined in Table A3), respectively, including variants thereof; the V H CDR1, V H CDR2, and V H CDR3 sequences comprise SEQ ID NOs: 12, 13, and 14, respectively, and the V L CDR1, V L CDR2, and V L CDR3 sequences comprise SEQ ID NOs: 15, 16, and 17, respectively, including variants thereof with 1, 2, 3, 4, or 5 alterations in the CDR(s) and which specifically bind to the human HRS polypeptide; the V H CDR1, V H CDR2, and V H CDR3 sequences comprise SEQ ID NOs: 18, 19, and 20, respectively, and the V L CDR1, V L CDR2, and V L CDR3 sequences comprise SEQ ID NOS: 21, 22, and 23, respectively, including variants thereof with 1, 2, 3, 4, or 5 alterations in the CDR(s) and which specifically bind to the human HRS polypeptide; the V H CDR1, V H CDR2, and V H CDR3 sequences comprise SEQ ID NOs: 24, 25, and 26, respectively, and the V L CDR1, V L CDR2, and V L CDR3 sequences comprise SEQ ID NOs: 27, 28, and 29, respectively, including variants thereof with 1, 2, 3, 4, or 5 alterations in the CDR(s) and which specifically bind to the human HRS polypeptide; the V H CDR1, V H CDR2, and V H CDR3 sequences comprise SEQ ID NOs: 36, 37, and 38, respectively, and the V L CDR1, V L CDR2, and V L CDR3 sequences comprise SEQ ID NOs: 39, 40, and 41, respectively, including variants thereof; the V H CDR1, V H CDR2, and V H CDR3 sequences comprise SEQ ID NOs: 42, 43, and 44, respectively, and the V L CDR1, V L CDR2, and V L CDR3 sequences comprise SEQ ID NOs: 45, 46, and 47, respectively, including variants thereof; the V H CDR1, V H CDR2, and V H CDR3 sequences comprise SEQ ID NOs: 48, 49, and 50, respectively, and the V L CDR1, V L CDR2, and V L CDR3 sequences comprise SEQ ID NOs: 51, 52, and 53, respectively, including variants thereof; the V H CDR1, V H CDR2, and V H CDR3 sequences comprise SEQ ID NOs: 54, 55, and 56, respectively, and the V L CDR1, V L CDR2, and V L CDR3 sequences comprise SEQ ID NOs: 57, 58, and 59, respectively, including variants thereof; the V H CDR1, V H CDR2, and V H CDR3 sequences comprise SEQ ID NOs: 60, 61, and 62, respectively, and the V L CDR1, V L CDR2, and V L CDR3 sequences comprise SEQ ID NOS: 63, 64, and 65, respectively, including variants thereof; the V H CDR1, V H CDR2, and V H CDR3 sequences comprise SEQ ID NOs: 66, 67, and 68, respectively, and the V L CDR1, V L CDR2, and V L CDR3 sequences comprise SEQ ID NOs: 69, 70, and 71, respectively, including variants thereof; the V H CDR1, V H CDR2, and V H CDR3 sequences comprise SEQ ID NOs: 72, 73, and 74, respectively, and the V L CDR1, V L CDR2, and V L CDR3 sequences comprise SEQ ID NOs: 75, 76, and 77, respectively, including variants thereof; the V H CDR1, V H CDR2, and V H CDR3 sequences comprise SEQ ID NOs: 78, 79, and 80, respectively, and the V L CDR1, V L CDR2, and V L CDR3 sequences comprise SEQ ID NOS: 81, 82, and 83, respectively, including variants thereof; the V H CDR1, V H CDR2, and V H CDR3 sequences comprise SEQ ID NOs: 84, 85, and 86, respectively, and the V L CDR1, V L CDR2, and V L CDR3 sequences comprise SEQ ID NOs: 87, 88, and 89, respectively, including variants thereof; the V H CDR1, V H CDR2, and V H CDR3 sequences comprise SEQ ID NOs: 90, 91, and 92, respectively, and the V L CDR1, V L CDR2, and V L CDR3 sequences comprise SEQ ID NOs: 93, 94, and 95, respectively, including variants thereof; the V H CDR1, V H CDR2, and V H CDR3 sequences comprise SEQ ID NOs: 96, 97, and 98, respectively, and the V L CDR1, V L CDR2, and V L CDR3 sequences comprise SEQ ID NOs: 99, 100, and 101, respectively, including variants thereof; the V H CDR1, V H CDR2, and V H CDR3 sequences comprise SEQ ID NOs: 102, 103, and 104, respectively, and the V L CDR1, V L CDR2, and V L CDR3 sequences comprise SEQ ID NOS: 105, 106, and 107, respectively, including variants thereof; the V H CDR1, V H CDR2, and V H CDR3 sequences comprise SEQ ID NOs: 108, 109, and 110, respectively, and the V L CDR1, V L CDR2, and V L CDR3 sequences comprise SEQ ID NOs: 111, 112, and 113, respectively, including variants thereof; the V H CDR1, V H CDR2, and V H CDR3 sequences comprise SEQ ID NOs: 114, 115, and 116, respectively, and the V L CDR1, V L CDR2, and V L CDR3 sequences comprise SEQ ID NOs: 117, 118, and 119, respectively, including variants thereof; the V H CDR1, V H CDR2, and V H CDR3 sequences comprise SEQ ID NOs: 120, 121, and 122, respectively, and the V L CDR1, V L CDR2, and V L CDR3 sequences comprise SEQ ID NOs: 123, 124, and 125, respectively, including variants thereof; the V H CDR1, V H CDR2, and V H CDR3 sequences comprise SEQ ID NOs: 126, 127, and 128, respectively, and the V L CDR1, V L CDR2, and V L CDR3 sequences comprise SEQ ID NOs: 129, 130, and 131, respectively, including variants thereof; the V H CDR1, V H CDR2, and V H CDR3 sequences comprise SEQ ID NOs: 132, 133, and 134, respectively, and the V L CDR1, V L CDR2, and V L CDR3 sequences comprise SEQ ID NOs: 135, 136, and 137, respectively, including variants thereof; the V H CDR1, V H CDR2, and V H CDR3 sequences comprise SEQ ID NOs: 138, 139, and 140, respectively, and the V L CDR1, V L CDR2, and V L CDR3 sequences comprise SEQ ID NOs: 141, 142, and 143, respectively, including variants thereof; the V H CDR1, V H CDR2, and V H CDR3 sequences comprise SEQ ID NOs: 144, 145, and 146, respectively, and the V L CDR1, V L CDR2, and V L CDR3 sequences comprise SEQ ID NOs: 147, 148, and 149, respectively, including variants thereof; the V H CDR1, V H CDR2, and V H CDR3 sequences comprise SEQ ID NOs: 150, 151, and 152, respectively, and the V L CDR1, V L CDR2, and V L CDR3 sequences comprise SEQ ID NOs: 153, 154, and 155, respectively, including variants thereof; the V H CDR1, V H CDR2, and V H CDR3 sequences comprise SEQ ID NOs: 156, 157, and 158, respectively, and the V L CDR1, V L CDR2, and V L CDR3 sequences comprise SEQ ID NOS: 159, 160, and 161, respectively, including variants thereof; the V H CDR1, V H CDR2, and V H CDR3 sequences comprise SEQ ID NOs: 162, 163, and 164, respectively, and the V L CDR1, V L CDR2, and V L CDR3 sequences comprise SEQ ID NOs: 165, 166, and 167, respectively, including variants thereof; the V H CDR1, V H CDR2, and V H CDR3 sequences comprise SEQ ID NOs: 168, 169, and 170, respectively, and the V L CDR1, V L CDR2, and V L CDR3 sequences comprise SEQ ID NOs: 171, 172, and 173, respectively, including variants thereof; the V H CDR1, V H CDR2, and V H CDR3 sequences comprise SEQ ID NOs: 174, 175, and 176, respectively, and the V L

Assignees

• Atyr Pharma Inc

Inventors

• Adams Ryan Andrew
• Burman Luke
• Chong Yeeting
• King David
• Mendlein John D
• Greene Leslie Nangle
• Ogilvie Kathleen
• Rauch Kaitlyn

Classifications

• C07K2317/76

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

• C07K16/18 Primary

  against material from animals or humans · CPC title

• A61K39/39541

  against normal tissues, cells · CPC title

• A61P35/04 Primary

  specific for metastasis · CPC title

• C07K16/2827

  against B7 molecules, e.g. CD80, CD86 · CPC title