Methods and compositions relating to anti-Chi3l1 antibody reagents

Patent metadata

Field	Value
Publication number	US-10253111-B2
Application number	US-201816124558-A
Country	US
Kind code	B2
Filing date	Sep 7, 2018
Priority date	Jan 5, 2017
Publication date	Apr 9, 2019
Grant date	Apr 9, 2019

Abstract

Described herein are methods and compositions relating to anti-Chi3L1 antibodies, antibody reagents, and antigen-binding fragments thereof which display superior properties, e.g., high sensitivity, high specificity, high binding affinity, neutralization activity ex vivo and in vivo (e.g., blocks Chi3L1-induced MAPK and AKT signaling). Methods of treatment, e.g., of treating cancer, obesity, and/or asthma by administering the compounds described herein are also provided.

First claim

What is claimed herein is:

1. An antibody, antibody reagent, antigen-binding fragment thereof, or chimaeric antigen receptor (CAR), that specifically binds an CHI3L1 polypeptide, said antibody, antibody reagent, antigen-binding portion thereof, or CAR comprising the complementarity determining regions (CDRs) of:
(a) a light chain CDR1 having the amino acid sequence of SEQ ID NO: 4;
(b) a light chain CDR2 having the amino acid sequence of SEQ ID NO: 5;
(c) a light chain CDR3 having the amino acid sequence of SEQ ID NO: 6;
(d) a heavy chain CDR1 having the amino acid sequence of SEQ ID NO: 1;
(e) a heavy chain CDR2 having the amino acid sequence of SEQ ID NO: 2; and
(f) a heavy chain CDR3 having the amino acid sequence of SEQ ID NO: 3.

2. The antibody, antibody reagent, antigen-binding portion thereof, or CAR of claim 1 , comprising a heavy chain sequence having the amino acid sequence of SEQ ID NO: 36.

3. The antibody, antibody reagent, antigen-binding portion thereof, or CAR of claim 1 , comprising a light chain sequence having the amino acid sequence of SEQ ID NO: 38.

4. The antibody, antibody reagent, antigen-binding portion thereof, or CAR of claim 1 , comprising a heavy chain sequence having the amino acid sequence of SEQ ID NO: 36 and a light chain sequence having the amino acid sequence of SEQ ID NO: 38.

5. The antibody, antibody reagent, antigen-binding portion thereof, or CAR of claim 1 , further comprising a conservative substitution relative to the heavy chain sequence having the amino acid sequence of SEQ ID NO: 36 or the light chain sequence having the amino acid sequence of SED ID NO: 38, wherein the conservative substitution is in a sequence not comprised by a CDR.

6. The antibody, antibody reagent, antigen-binding portion thereof, or CAR of claim 1 , wherein the antibody, antibody reagent, antigen-binding fragment thereof, or CAR is fully humanized except for the CDRsequences.

7. The antibody, antibody reagent, antigen-binding portion thereof, or CAR of claim 1 , wherein the antibody, antibody reagent, antigen-binding fragment thereof, or CAR is selected from the group consisting of:
an immunoglobulin molecule, a monoclonal antibody, a chimeric antibody, a CDR-grafted antibody, a humanized antibody, a Fab, a Fab′, a F(ab′)2, a Fv, a disulfide linked Fv, a scFv, a diabody, a multispecific antibody, a dual specific antibody, an anti-idiotypic antibody, and a bispecific antibody.

8. A nucleic acid sequence encoding the antibody, antibody reagent, antigen-binding fragment thereof, or CAR of claim 1 .

9. The nucleic acid sequence of claim 8 , wherein at least one CDR is encoded by a nucleic acid sequence selected from SEQ ID NOs: 7-12.

10. The nucleic acid sequence of claim 8 , comprising one or more sequences selected from SEQ ID NOs: 37 and 39.

11. An isolated cell comprising the antibody, antibody reagent, antigen-binding fragment thereof, or CAR of claim 1 .

12. A pharmaceutical composition comprising the antibody, antibody reagent, antigen-binding fragment thereof, or CAR of claim 1 , and a pharmaceutically acceptable carrier.

13. The pharmaceutical composition of claim 12 , further comprising a chemotherapeutic agent.

14. The composition of claim 13 , wherein the antibody, antibody reagent, or antigen-binding portion thereof is conjugated to the chemotherapeutic agent.

Assignees

• Univ Brown

Inventors

• Elias Jack A
• Lee Chun Geun
• He Chuan Hua
• Ma Bing
• Kamle Suchitra
• Lee Chang-Min

Classifications

• G01N33/53

  Immunoassay; Biospecific binding assay; Materials therefor · CPC title

• A61P31/04

  Antibacterial agents · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61K2039/505

  comprising antibodies · CPC title

• C07K16/40 Primary

  against enzymes · CPC title