Anti-ror1 chimeric antigen receptors

Patent metadata

Field	Value
Publication number	US-2018147271-A1
Application number	US-201615575220-A
Country	US
Kind code	A1
Filing date	May 17, 2016
Priority date	May 18, 2015
Publication date	May 31, 2018
Grant date	—

Abstract

The invention provides improved compositions for adoptive cell therapies for cancers that express ROR1.

First claim

1 . A chimeric antigen receptor (CAR) comprising: an extracellular domain that comprises:
a) an anti-receptor tyrosine kinase-like orphan receptor 1 (ROR1) antibody or antigen binding fragment thereof that binds one or more epitopes of a human ROR1 polypeptide, wherein the anti-ROR1 antibody or antigen binding fragment thereof comprises a variable light chain sequence comprising CDRL1-CDRL3 sequences set forth in SEQ ID NOs: 1-3, 9-11, 17-19, 25-27, 33-35, 41-43, 49-51, 57-59, 65-67, 73-75, 81-83, 89-91, 97-99, 105-107, 113-115, 121-123, 129-131, 137-139, 145-147, 153-155, 161-163, 169-171, 177-179, 185-187, 193-195, 201-203, 209-211, 217-219, 225-227, 233-235, 241-243, 249-251, 257-259, 265-267, 273-275, 281-283, 289-291, 297-299, 305-307, 313-315, 321-323, 329-331, 337-339, 345-347, or 353-355, and a variable heavy chain sequence comprising CDRH1-CDRH3 sequences set forth in SEQ ID NOs: 4-6, 12-14, 20-22, 28-30, 36-38, 44-46, 52-54, 60-62, 68-70, 76-78, 84-86, 92-94, 100-102, 108-110, 116-118, 124-126, 132-134, 140-142, 148-150, 156-158, 164-166, 172-174, 180-182, 188-190, 196-198, 204-206, 212-214, 220-222, 228-230, 236-238, 244-246, 252-254, 260-262, 268-270, 276-278, 284-286, 292-294, 300-302, 308-310, 316-318, 324-326, 332-334, 340-342, 348-350, or 356-358; b) a transmembrane domain; c) one or more intracellular co-stimulatory signaling domains; and d) a primary signaling domain.

2 . The CAR of claim 1 , wherein the anti-ROR1 antibody or antigen binding fragment that binds the human ROR1 polypeptide is selected from the group consisting of: a Camel Ig, Ig NAR, Fab fragments, Fab′ fragments, F(ab)′2 fragments, F(ab)′3 fragments, Fv, single chain Fv antibody (“scFv”), bis-scFv, (scFv)2, minibody, diabody, triabody, tetrabody, disulfide stabilized Fv protein (“dsFv”), and single-domain antibody (sdAb, Nanobody).

3 . The CAR of claim 2 , wherein the anti-ROR1 antibody or antigen binding fragment that binds the human ROR1 polypeptide is an scFv.

4 . The CAR of any one of claims 1 to 3 , wherein the anti-ROR1 antibody or antigen binding fragment thereof comprises one or more light chain CDRs as set forth in any one of SEQ ID NOs: 1-3 and/or one or more heavy chain CDRs as set forth in any one of SEQ ID NOs: 4-6.

5 . The CAR of any one of claims 1 to 3 , wherein the anti-ROR1 antibody or antigen binding fragment thereof comprises one or more light chain CDRs as set forth in any one of SEQ ID NOs: 9-11 and/or one or more heavy chain CDRs as set forth in any one of SEQ ID NOs: 12-14.

6 . The CAR of any one of claims 1 to 3 , wherein the anti-ROR1 antibody or antigen binding fragment thereof comprises one or more light chain CDRs as set forth in any one of SEQ ID NOs: 17-19 and/or one or more heavy chain CDRs as set forth in any one of SEQ ID NOs: 20-22.

7 . The CAR of any one of claims 1 to 3 , wherein the anti-ROR1 antibody or antigen binding fragment thereof comprises one or more light chain CDRs as set forth in any one of SEQ ID NOs: 25-27 and/or one or more heavy chain CDRs as set forth in any one of SEQ ID NOs: 28-30.

8 . The CAR of any one of claims 1 to 3 , wherein the anti-ROR1 antibody or antigen binding fragment thereof comprises one or more light chain CDRs as set forth in any one of SEQ ID NOs: 33-35 and/or one or more heavy chain CDRs as set forth in any one of SEQ ID NOs: 36-38.

9 . The CAR of any one of claims 1 to 3 , wherein the anti-ROR1 antibody or antigen binding fragment thereof comprises one or more light chain CDRs as set forth in any one of SEQ ID NOs: 41-43 and/or one or more heavy chain CDRs as set forth in any one of SEQ ID NOs: 44-46.

10 . The CAR of any one of claims 1 to 3 , wherein the anti-ROR1 antibody or antigen binding fragment thereof comprises one or more light chain CDRs as set forth in any one of SEQ ID NOs: 49-51 and/or one or more heavy chain CDRs as set forth in any one of SEQ ID NOs:
52-54.

11 . The CAR of any one of claims 1 to 3 , wherein the anti-ROR1 antibody or antigen binding fragment thereof comprises one or more light chain CDRs as set forth in any one of SEQ ID NOs: 57-59 and/or one or more heavy chain CDRs as set forth in any one of SEQ ID NOs: 60-62.

12 . The CAR of any one of claims 1 to 3 , wherein the anti-ROR1 antibody or antigen binding fragment thereof comprises one or more light chain CDRs as set forth in any one of SEQ ID NOs: 65-67 and/or one or more heavy chain CDRs as set forth in any one of SEQ ID NOs: 68-70.

13 . The CAR of any one of claims 1 to 3 , wherein the anti-ROR1 antibody or antigen binding fragment thereof comprises one or more light chain CDRs as set forth in any one of SEQ ID NOs: 73-75 and/or one or more heavy chain CDRs as set forth in any one of SEQ ID NOs: 76-78.

14 . The CAR of any one of claims 1 to 3 , wherein the anti-ROR1 antibody or antigen binding fragment thereof comprises one or more light chain CDRs as set forth in any one of SEQ ID NOs: 81-83 and/or one or more heavy chain CDRs as set forth in any one of SEQ ID NOs: 84-86.

15 . The CAR of any one of claims 1 to 3 , wherein the anti-ROR1 antibody or antigen binding fragment thereof comprises one or more light chain CDRs as set forth in any one of SEQ ID NOs: 89-91 and/or one or more heavy chain CDRs as set forth in any one of SEQ ID NOs: 92-94.

16 . The CAR of any one of claims 1 to 3 , wherein the anti-ROR1 antibody or antigen binding fragment thereof comprises one or more light chain CDRs as set forth in any one of SEQ ID NOs: 97-99 and/or one or more heavy chain CDRs as set forth in any one of SEQ ID NOs: 100-102.

17 . The CAR of any one of claims 1 to 3 , wherein the anti-ROR1 antibody or antigen binding fragment thereof comprises one or more light chain CDRs as set forth in any one of SEQ ID NOs: 105-107 and/or one or more heavy chain CDRs as set forth in any one of SEQ ID NOs: 108-110.

18 . The CAR of any one of claims 1 to 3 , wherein the anti-ROR1 antibody or antigen binding fragment thereof comprises one or more light chain CDRs as set forth in any one of SEQ ID NOs: 113-115 and/or one or more heavy chain CDRs as set forth in any one of SEQ ID NOs: 116-118.

19 . The CAR of any one of claims 1 to 3 , wherein the anti-ROR1 antibody or antigen binding fragment thereof comprises one or more light chain CDRs as set forth in any one of SEQ ID NOs: 121-123 and/or one or more heavy chain CDRs as set forth in any one of SEQ ID NOs: 124-126.

20 . The CAR of any one of claims 1 to 3 , wherein the anti-ROR1 antibody or antigen binding fragment thereof comprises one or more light chain CDRs as set forth in any one of SEQ ID NOs: 129-131 and/or one or more heavy chain CDRs as set forth in any one of SEQ ID NOs: 132-134.

21 . The CAR of any one of claims 1 to 3 , wherein the anti-ROR1 antibody or antigen binding fragment thereof comprises one or more light chain CDRs as set forth in any one of SEQ ID NOs: 137-139 and/or one or more heavy chain CDRs as set forth in any one of SEQ ID NOs: 140-142.

22 . The CAR of any one of claims 1 to 3 , wherein the anti-ROR1 antibody or antigen binding fragment thereof comprises one or more light chain CDRs as set forth in any one of SEQ ID NOs: 145-147 and/or one or more heavy chain CDRs as set forth in any one of SEQ ID NOs: 148-150.

23 . The CAR of any one of claims 1 to 3 , wherein the anti-ROR1 antibody or antigen binding fragment thereof comprises one or more light chain CDRs as set forth in any one of SEQ ID NOs: 153-155 and/or

Assignees

• Bluebird Bio Inc
• Five Prime Therapeutics Inc
• Eureka Therapeutics Inc

Inventors

• Morgan Richard
• Sikorski Robert
• Wong Brian
• Masteller Emma
• Borges Luis
• Liu Cheng
• Xu Yiyang

Classifications

• C07K2317/73

  Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation · CPC title

• C07K16/2803

  against the immunoglobulin superfamily · CPC title

• C07K16/30

  from tumour cells · CPC title

• A61K2039/505

  comprising antibodies · CPC title

• C07K2317/622

  Single chain antibody (scFv) · CPC title