# US 11,110,096 B2 · Combination therapies

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- Number: US 11,110,096 B2
- Document ID: US11110096B2
- Status: Granted
- Kind: B2
- Application number: 15/587,208
- Filed: 2017-05-04
- Published: 2018-03-01
- Granted: 2021-09-07
- Earliest claimed: 2014-04-16
- Assignees: Infinity Pharmaceuticals, Inc.
- Applicants: Infinity Pharmaceuticals, Inc.
- Inventors: Jeffery L. Kutok; Howard M. Stern
- Web page: https://patentgrep.com/patent/US11110096B2

## CPC

- A61K 31/52: Purines, e.g. adenine
- A61K 31/437: the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
- A61K 31/496: Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
- A61K 31/5377: not condensed and containing further heterocyclic rings, e.g. timolol
- 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

Provided herein are pharmaceutical compositions comprising a phosphatidylinositol 3-kinase inhibitor or a pharmaceutically acceptable form thereof, and a Bcl-2 inhibitor or a pharmaceutically acceptable form thereof. Also provided herein are methods for treating cancer comprising administration the compositions, and uses of the compositions, e.g., for the treatment of cancer.

## Claims

### Claim 1

A method of treating a hematological cancer in a human subject in need thereof, comprising administering to the subject a combination of (S)-3-(1-((9H-purin-6-yl)amino)ethyl)-8-chloro-2-phenylisoquinolin-1(2H)-one (Compound 1), or a pharmaceutically acceptable salt or hydrate thereof, and ABT-199, or a pharmaceutically acceptable salt thereof;
wherein Compound 1, or a pharmaceutically acceptable salt or hydrate thereof, is administered at a dose of about 15 mg to about 75 mg;
wherein ABT-199, or a pharmaceutically acceptable salt thereof, is administered at a dose of about 10 mg to about 400 mg; and
wherein the hematological cancer is selected from the group consisting of chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), CLL/SLL, indolent NHL (iNHL), diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma (MCL), T-cell lymphoma (TCL), peripheral T-cell lymphoma (PTCL), cutaneous T-cell lymphoma (CTCL), follicular lymphoma (FL), and Richter's syndrome.

### Claim 2 (depends on 1)

The method of claim 1, wherein Compound 1 is at an amount sufficient to reach maximum plasma concentration at steady state (Cmaxss) at about 1000 ng/mL to about 5000 ng/mL; and the Bcl-2 inhibitor is administered at an amount to reach Cmaxss at about 0.1 μg/mL to about 1000 μg/mL.

### Claim 3 (depends on 1)

The method of claim 1, wherein Compound 1 is at an amount sufficient to reach an area under the plasma concentration-time curve at steady state (AUCss) at about 5000 ng/mL*hr to about 10000 ng/mL*hr; and the Bcl-2 inhibitor is administered at an amount to reach an AUCss at about 0.1 ng/mL*hr to about 10000 ng/mL*hr.

### Claim 4 (depends on 1)

The method of claim 1, wherein the cancer is a diffuse large B-cell lymphoma (DLBCL).

### Claim 5 (depends on 1)

The method of claim 1, wherein the cancer is an indolent non-Hodgkin's lymphoma (iNHL).

### Claim 6 (depends on 1)

The method of claim 1, wherein the cancer is a follicular lymphoma (FL).

### Claim 7 (depends on 1)

The method of claim 1, wherein the cancer is a mantle cell lymphoma (MCL).

### Claim 8 (depends on 1)

The method of claim 1, wherein the cancer is a T-cell lymphoma.

### Claim 9 (depends on 1)

The method of claim 1, wherein the cancer is chronic lymphocytic leukemia (CLL).

### Claim 10 (depends on 1)

The method of claim 1, wherein the hematological cancer is small lymphocytic lymphoma (SLL).

### Claim 11 (depends on 1)

The method of claim 1, wherein the hematological cancer is CLL, SLL, CLL/SLL, or Richter's syndrome.

### Claim 12 (depends on 1)

The method of claim 1, wherein CLL, SLL, or CLL/SLL is relapsed or refractory CLL, SLL, or CLL/SLL.

### Claim 13 (depends on 1)

The method of claim 1, wherein Compound 1, or a pharmaceutically acceptable salt or hydrate thereof, is administered at a dose of about 25 mg.

### Claim 14 (depends on 1)

The method of claim 1, wherein Compound 1, or a pharmaceutically acceptable salt or hydrate thereof, is administered BID.

### Claim 15 (depends on 13)

The method of claim 13, wherein Compound 1, or a pharmaceutically acceptable salt or hydrate thereof, is administered BID.

### Claim 16 (depends on 1)

The method of claim 1, wherein ABT-199, or a pharmaceutically acceptable salt thereof, is administered at once per day.