Methods and compositions relating to anti-CHI3L1 antibody reagents for the treatment of cancer

Patent metadata

Field	Value
Publication number	US-11667725-B2
Application number	US-202016939265-A
Country	US
Kind code	B2
Filing date	Jul 27, 2020
Priority date	Jan 5, 2017
Publication date	Jun 6, 2023
Grant date	Jun 6, 2023

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. A method of treating cancer in a subject in need thereof, the method comprising administering, to the subject, an immunoglobulin antibody that specifically binds an CHI3L1 polypeptide, said immunoglobulin antibody comprising 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;

wherein the cancer expresses CHI3L1.

2. The method of claim 1 , wherein the immunoglobulin antibody comprises a heavy chain sequence having the amino acid sequence of SEQ ID NO: 36 or a light chain sequence having the amino acid sequence of SEQ ID NO: 38.

3. The method of claim 1 , wherein the immunoglobulin antibody comprises 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.

4. The method of claim 1 , wherein the immunoglobulin antibody comprises 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 SEQ ID NO: 38, wherein the conservative substitution is in a sequence not comprised by a CDR.

5. The method of claim 1 , wherein the immunoglobulin antibody is selected from the group consisting of:
an immunoglobulin antibody which is fully humanized except for the CDR sequences; a monoclonal antibody, a CDR-grafted antibody, and a humanized antibody.

6. The method of claim 1 , wherein the immunoglobulin antibody binds a CHI3L1 polypeptide at an epitope having the amino acid sequences of SEQ ID NO: 13.

7. The method of claim 1 , wherein the immunoglobulin antibody is administered in a pharmaceutical composition comprising the antibody and a pharmaceutically acceptable carrier.

8. The method of claim 1 , wherein the subject is a subject determined to have a level of CHI3L1 that is increased compared to a reference level from healthy subjects.

9. The method of claim 8 , wherein the CHI3L1 is circulating CHI3L1.

10. The method of claim 1 , wherein the subject is a subject determined to have a level of CHI3L1 that is increased compared to the level of CHI3L1 in a prior sample obtained from the subject.

11. The method of claim 10 , wherein the CHI3L1 is circulating CHI3L1.

12. The method of claim 1 , wherein the cancer is primary cancer.

13. The method of claim 1 , wherein the cancer is malignant cancer.

14. The method of claim 1 , wherein the cancer is selected from the group consisting of:
prostate cancer, colon cancer, rectal cancer, ovarian cancer, kidney cancer, breast cancer, glioblastoma, melanoma, malignant melanoma, and lung cancer.

15. The method of claim 1 , wherein the subject is further administered a chemotherapeutic agent.

Assignees

• Univ Brown

Inventors

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

Classifications

• A61P3/04

  Anorexiants; Antiobesity agents · CPC title

• A61P19/02

  for joint disorders, e.g. arthritis, arthrosis · CPC title

• A61P31/04

  Antibacterial agents · CPC title

• A61P35/04

  specific for metastasis · CPC title

• A61K2039/505

  comprising antibodies · CPC title