# US 10,766,968 B2 · Methods and compositions relating to anti-CHI3L1 antibody reagents to treat cancer

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- Number: US 10,766,968 B2
- Document ID: US10766968B2
- Status: Granted
- Kind: B2
- Application number: 16/124,575
- Filed: 2018-09-07
- Published: 2019-02-28
- Granted: 2020-09-08
- Earliest claimed: 2017-08-23
- Assignees: Brown University
- Applicants: Brown University
- Inventors: Jack A. Elias; Chun Geun Lee; Chuan Hua He; Bing Ma; Suchitra Kamle; Chang-Min Lee
- Web page: https://patentgrep.com/patent/US10766968B2

## CPC

- A61P 35/00: Antineoplastic agents
- C07K 16/40: against enzymes
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61P 11/06: Antiasthmatics
- A61P 35/04: specific for metastasis
- C07K 16/2803: {against the immunoglobulin superfamily}
- C07K 16/2818: {against CD28 or CD152}
- C07K 16/2839: {against the integrin superfamily}
- A61K 2039/505: {comprising antibodies}
- A61K 2039/507: {Comprising a combination of two or more separate antibodies}
- A61K 2300/00: Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
- C07K 2317/34: Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues
- C07K 2317/73: Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
- C07K 2317/76: Antagonist effect on antigen, e.g. neutralization or inhibition of binding
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00)
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)

## Abstract

It is demonstrated herein that inhibitors of immune checkpoints and CHI3L1 are synergistic. Accordingly, described herein are methods and compositions relating to combinatorial therapies for cancer, e.g., comprising an inhibitor of CHI3L1; and an inhibitor of an immune checkpoint protein. In some embodiments, the CHI3L1 inhibitor can be an antibody or antibody reagent as described herein.

## Claims

### Claim 1

A method of treating cancer in a subject in need thereof, the method comprising administering:
a) an antibody, antibody reagent, or antigen-binding fragment thereof, that specifically binds to PD-1; and
b) an inhibitor of CHI3L1, wherein the inhibitor of CHI3L1 is an immunoglobulin antibody that comprises light chain CDRs having the amino acid sequences of SEQ ID NOs: 4-6 and heavy chain CDRs having the amino acid sequences of SEQ ID NOs: 1-3,
wherein the cancer expresses PD-L1 and CHI3L1.

### Claim 2 (depends on 1)

The method of claim 1, wherein the inhibitor of CHI3L1 binds a CHI3L1 polypeptide at an epitope selected from SEQ ID NO: 13.

### Claim 3 (depends on 1)

The method of claim 1, wherein the cancer is a primary cancer or a metastatic cancer.

### Claim 4 (depends on 1)

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

### Claim 5 (depends on 1)

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.

### Claim 6 (depends on 1)

The method of claim 1, wherein the antibody, antibody reagent, or antigen-binding fragment thereof, that specifically binds to PD-1 is selected from the group consisting of:
pembrolizumab; nivolumab and pidilizumab.

### Claim 7 (depends on 1)

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

### Claim 8 (depends on 7)

The method of claim 7, wherein the CHI3L1 is circulating CHI3L1.