Pilra antibodies and methods of use thereof

Patent metadata

Field	Value
Publication number	US-2024425587-A1
Application number	US-202218686156-A
Country	US
Kind code	A1
Filing date	Aug 24, 2022
Priority date	Aug 25, 2021
Publication date	Dec 26, 2024
Grant date	—

Abstract

The present disclosure provides antibodies and antigen-binding fragments thereof that specifically bind to human PILRA and compositions comprising such antibodies or antigen-binding fragments thereof. In a particular aspect, the antibodies or antigen-binding fragments thereof that specifically bind to human PILRA block binding of PILRA to ligand, block binding of soluble PILRA to T cells, and/or decrease cell surface PILRA. In further aspects, the antibodies or antigen-binding fragments can be used to treat diseases or conditions associated with myeloid cell dysfunction.

First claim

What is claimed:

1 . An isolated antibody or antigen-binding fragment thereof that specifically binds to human PILRA and to cynomolgus PILRA, wherein the antibody or antigen-binding fragment thereof (a) does not bind to human PILRB and (b) blocks binding of soluble human PILRA to T-cells.

2 . The antibody or antigen-binding fragment thereof of claim 1 , wherein the antibody or antigen-binding fragment downregulates cell surface human PILRA.

3 . The antibody or antigen-binding fragment thereof of claim 1 or 2 , wherein the antibody or antigen-binding fragment does not block binding of human PILRA to one or more of its ligands.

4 . The antibody or antigen-binding fragment of any one of claims 1-3 , wherein the antibody or antigen-binding comprises the heavy chain variable region (VH) complementarity determining region (CDR) 1, VH CDR2, VH CDR3 and light chain variable region (VL) CDR1, CDR2, and CDR3 sequences of:
(a) SEQ ID NOs: 244-249, respectively; (b) SEQ ID NOs: 308-311, 38, and 313, respectively; or (c) SEQ ID NOs: 314-319, respectively.

5 . The antibody or antigen-binding fragment of any one of claims 1-3 , wherein the antibody or antigen-binding comprises a heavy chain variable region and a light chain variable region comprising the amino acid sequences of:
(a) SEQ ID NOs: 268 and 269, respectively; (b) SEQ ID NOs: 344 and 345, respectively; or (c) SEQ ID NOs: 346 and 347, respectively.

6 . The antibody or antigen-binding fragment thereof of claim 1 or 2 , wherein the antibody or antigen-binding fragment blocks binding of human PILRA to one or more of its ligands.

7 . The antibody or antigen-binding fragment of any one of claims 1, 2, and 6 , wherein the antibody or antigen-binding comprises the heavy chain variable region (VH) complementarity determining region (CDR) 1, VH CDR2, VH CDR3 and light chain variable region (VL) CDR1, CDR2, and CDR3 sequences of:
(a) SEQ ID NOs: 22-27, respectively; (b) SEQ ID NOs: 28-31, 26, and 33, respectively; (c) SEQ ID NOs: 34-39, respectively; (d) SEQ ID NOs: 40, 23, 36, and 43-45, respectively; (e) SEQ ID NOs: 46, 23, 48, 49, 38, and 51, respectively; (f) SEQ ID NOs: 52-55, 38, and 57, respectively; or (g) SEQ ID NOs: 58, 5, and 60-63, respectively.

8 . The antibody or antigen-binding fragment of any one of claims 1, 2, 6, and 7 , wherein the antibody or antigen-binding comprises a heavy chain variable region and a light chain variable region comprising the amino acid sequences of:
(a) SEQ ID NOs: 100 and 101, respectively; (b) SEQ ID NOs: 102 and 103, respectively; (c) SEQ ID NOs: 104 and 105, respectively; (d) SEQ ID NOs: 106 and 107, respectively; (e) SEQ ID NOs: 108 and 109, respectively; (f) SEQ ID NOs: 108 and 727, respectively; (g) SEQ ID NOs: 110 and 111, respectively; or (h) SEQ ID NOs: 112 and 113, respectively.

9 . An isolated antibody or antigen-binding fragment thereof that specifically binds to human PILRA, wherein the antibody or antigen-binding fragment thereof (a) does not bind to cynomolgus PILRA, and (b) blocks binding of soluble human PILRA to T-cells.

10 . The antibody or antigen-binding fragment of claim 9 , wherein the antibody or antigen-binding comprises the heavy chain variable region (VH) complementarity determining region (CDR) 1, VH CDR2, VH CDR3 and light chain variable region (VL) CDR1, CDR2, and CDR3 sequences of:
(a) SEQ ID NOs: 404-409, respectively; (b) SEQ ID NOs: 308 and 411-415, respectively; (c) SEQ ID NOs: 416-421, respectively; (d) SEQ ID NOs: 422-424, 407, 408, and 427, respectively; (e) SEQ ID NOs: 428-433, respectively; or (f) SEQ ID NOs: 452-455, 432, and 457, respectively.

11 . The antibody or antigen-binding fragment of claim 9 or 10 , wherein the antibody or antigen-binding comprises a heavy chain variable region and a light chain variable region comprising the amino acid sequences of:
(a) SEQ ID NOs: 458 and 459, respectively; (b) SEQ ID NOs: 460 and 461, respectively; (c) SEQ ID NOs: 462 and 463, respectively; (d) SEQ ID NOs: 464 and 465, respectively; (e) SEQ ID NOs: 466 and 467, respectively; or (f) SEQ ID NOs: 474 and 475, respectively.

12 . The antibody or antigen-binding fragment thereof of claim 9 , wherein the antibody or antigen-binding fragment does not block binding of human PILRA to one or more of its ligands.

13 . The antibody or antigen-binding fragment thereof of claim 9 , wherein the antibody or antigen-binding fragment blocks binding of human PILRA to one or more of its ligands.

14 . The antibody or antigen-binding fragment of any one of claims 9-11 , wherein the antibody or antigen-binding comprises the heavy chain variable region (VH) complementarity determining region (CDR) 1, VH CDR2, VH CDR3 and light chain variable region (VL) CDR1, CDR2, and CDR3 sequences of:
(a) SEQ ID NOs: 4-9, respectively; (b) SEQ ID NOs: 10-13, 8, and 15, respectively; (c) SEQ ID NOs: 16-21, respectively; (d) SEQ ID NOs: 52, 619, 620, 621, 408, and 623, respectively; or (e) SEQ ID NOs: 58, 804, 805, 673, 674, 675, respectively.

15 . The antibody or antigen-binding fragment of any one of claims 9, 13, or 14 , wherein the antibody or antigen-binding comprises a heavy chain variable region and a light chain variable region comprising the amino acid sequences of:
(a) SEQ ID NOs: 94 and 95, respectively; (b) SEQ ID NOs: 96 and 97, respectively; (c) SEQ ID NOs: 98 and 99, respectively; (d) SEQ ID NOs: 624 and 625, respectively; or (e) SEQ ID NOs: 710 and 728, respectively.

16 . The antibody or antigen-binding fragment thereof of any one of claims 9, 12, and 13 , wherein the antibody or antigen-binding fragment does not bind to human PILRB.

17 . The antibody or antigen-binding fragment thereof of any one of claims 9, 12, 13, and 16 , wherein the antibody or antigen-binding fragment thereof downregulates cell surface human PILRA.

18 . An isolated antibody or antigen-binding fragment thereof that specifically binds to human PILRA, to cynomolgus PILRA, and to human PILRB, and wherein the antibody or antigen-binding fragment blocks binding of soluble human PILRA to T-cells.

19 . The antibody or antigen-binding fragment thereof of claim 18 , wherein the antibody or antigen-binding fragment agonizes human PILRB.

20 . The antibody or antigen-binding fragment thereof of claim 18 or 19 , wherein the antibody or antigen-binding fragment downregulates cell surface human PILRA.

21 . The antibody or antigen-binding fragment of claim 18 , wherein the antibody or antigen-binding comprises the heavy chain variable region (VH) complementarity determining region (CDR) 1, VH CDR2, VH CDR3 and light chain variable region (VL) CDR1, CDR2, and CDR3 sequences of:
(a) SEQ ID NOs: 64-67, 8, and 69, respectively; (b) SEQ ID NOs: 58 and 71-75, respectively; (c) SEQ ID NOs: 76-79, 26, and 81, respectively; (d) SEQ ID NOs: 82-87, respectively; (e) SEQ ID NOs: 434-439, respectively; or (f) SEQ ID NOs: 440-445, respectively.

22 . The antibody or antigen-binding fragment of claim 18 or 21 , wherein the antibody or antigen-binding comprises a heavy chain variable region and a light chain variable region comprising the amino acid sequences of:
(a) SEQ ID NOs: 114 and 115, respectively; (b) SEQ ID NOs: 116 and 117, respectively; (c) SEQ ID NOs: 118 and 119, respectively; (d) SEQ ID NOs: 120 and 121, respectively; (e) SEQ ID NOs: 468 and 469, respectively; or (f) SEQ ID NOs: 470 and 471, respectively

Assignees

• Alector Llc

Inventors

• Nalle Samuel
• Liang Spencer
• Leung Ling
• Wang Yong
• Yee Angie Grace

Classifications

• A61K2039/505

  comprising antibodies · CPC title

• C07K2317/92

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

• C07K2317/626

  Diabody or triabody · CPC title

• C07K2317/622

  Single chain antibody (scFv) · CPC title

• C07K2317/569

  Single domain, e.g. dAb, sdAb, VHH, VNAR or nanobody® · CPC title