# US 11,304,952 B2 · Combination therapy using a chemokine receptor 2 (CCR2) antagonist and a PD-1/PD-L1 inhibitor

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- Number: US 11,304,952 B2
- Document ID: US11304952B2
- Status: Granted
- Kind: B2
- Application number: 16/139,745
- Filed: 2018-09-24
- Published: 2019-05-09
- Granted: 2022-04-19
- Earliest claimed: 2017-09-25
- Assignees: ChemoCentryx, Inc.
- Applicants: Chemocentryx, Inc.
- Inventors: James J. Campbell; Zhenhua Miao; Thomas J. Schall; Israel Charo; Shijie Li; Christine Marie Janson; Rajinder Singh; Karen Ebsworth
- Web page: https://patentgrep.com/patent/US11304952B2

## CPC

- A61K 31/536: ortho- or peri-condensed with carbocyclic ring systems
- A61K 31/165: having aromatic rings, e.g. colchicine, atenolol, progabide
- A61K 31/357: having two or more oxygen atoms in the same ring, e.g. crown ethers, guanadrel
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61P 35/00: Antineoplastic agents
- 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)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

The present disclosure is drawn to the combination therapy of a Chemokine Receptor 2 (CCR2) antagonist and a PD-1 and/or PD-L1 inhibitor in the treatment of cancer.

## Claims

### Claim 1

A method of treating colorectal cancer in a mammal, said method comprising administering a therapeutically effective amount of a CCR2 chemokine receptor antagonist and a therapeutically effective amount of a PD-1 and/or PD-L1 inhibitor, wherein said CCR2 chemokine receptor antagonist is a compound of Formula (Ia4)
or a pharmaceutically acceptable salt thereof; wherein
the subscripts m and n are each independently 1;
R3 is selected from the group consisting of C1-8 alkyl and C3-8 cycloalkyl;
R4 is selected from the group consisting of H and C1-8 alkyl;
the subscript p is 1 or 2;
each Rx is independently selected from the group consisting of halogen, —Rc, —ORa, —O—X1—ORa, and —X1—ORa, wherein each X1 is a C1-4 alkylene; each Ra is selected from hydrogen, C1-8 alkyl, and C1-8 haloalkyl; each Rc is independently selected from the group consisting of C1-8 alkyl and C1-8 haloalkyl;
the subscript q is 1 or 2;
each Rz is independently selected from the group consisting of halogen, —Ri, —CO2Rg, and tetrazole; wherein each R9 is selected from hydrogen, C1-8 alkyl, and C1-8 haloalkyl; each Ri is independently selected from the group consisting of C1-8 alkyl, and C1-8 haloalkyl.

### Claim 2 (depends on 1)

The method of claim 1, wherein the said CCR2 inhibitor has the formula
or a pharmaceutically acceptable salt thereof.

### Claim 3 (depends on 1)

The method of claim 1, wherein said CCR2 inhibitor has the formula
or a pharmaceutically acceptable salt thereof.

### Claim 4 (depends on 1)

The method of claim 1, wherein said CCR2 inhibitor has the formula
or a pharmaceutically acceptable salt thereof.

### Claim 5 (depends on 1)

The method of claim 1, wherein said PD-1 and/or PD-L1 inhibitor is a PD-1 inhibitor.

### Claim 6 (depends on 5)

The method of claim 5 wherein the PD-1 inhibitor is selected from the group consisting of pembrolizumab, nivolumab, IBI-308, mDX-400, BGB-108, MED-0680, SHR-1210, PF-06801591, PDR-001, GB-226, and STI-1110.

### Claim 7 (depends on 5)

The method of claim 5, wherein the PD-1 inhibitor is selected from the group consisting of Nivolumab, Pembrolizumab, and Pidilizumab.

### Claim 8 (depends on 1)

The method of claim 1, wherein said PD-1 and/or PD-L1 inhibitor is a PD-L1 inhibitor.

### Claim 9 (depends on 8)

The method of claim 8, wherein the PD-L1 inhibitor is selected from the group consisting of durvalumab, atezolizumab, avelumab, BMS-936559, ALN-PDL, TSR-042, KD-033, CA-170, CA-327, STI-1014, and KY-1003.

### Claim 10 (depends on 1)

The method of claim 1, wherein the CCR2 chemokine receptor antagonist and the PD-1 inhibitor and/or the PD-L1 inhibitor are administered concomitantly.

### Claim 11 (depends on 10)

The method of claim 10, wherein the CCR2 chemokine receptor antagonist, and the PD-1 inhibitor and/or the PD-L1 inhibitor are administered in a combination formulation.

### Claim 12 (depends on 1)

The method of claim 1, wherein the CCR2 chemokine receptor antagonist, and the PD-1 inhibitor and/or the PD-L1 inhibitor are administered sequentially.

### Claim 13 (depends on 12)

The method of claim 12, wherein the CCR2 chemokine receptor antagonist is administered prior to administration of the PD-1 inhibitor and/or the PD-L1 inhibitor.

### Claim 14 (depends on 12)

The method of claim 12, wherein the CCR2 chemokine receptor antagonist is administered after the administration of the PD-1 inhibitor and/or the PD-L1 inhibitor.

### Claim 15 (depends on 1)

The method of claim 1, wherein the CCR2 chemokine receptor antagonist is administered orally and the PD-1 inhibitor and/or the PD-L1 inhibitor is administered intravenously.

### Claim 16 (depends on 1)

The method of claim 1, wherein the mammal is a human subject.