# US 10,117,874 B2 · Combination of PI3K-inhibitors

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- Number: US 10,117,874 B2
- Document ID: US10117874B2
- Status: Granted
- Kind: B2
- Application number: 15/101,638
- Filed: 2014-11-28
- Published: 2016-10-20
- Granted: 2018-11-06
- Earliest claimed: 2013-12-03
- Assignees: Bayer Pharma Aktiengesellschaft
- Applicants: Bayer Pharma Aktiengesellschaft
- Inventors: Ningshu Liu
- Web page: https://patentgrep.com/patent/US10117874B2

## CPC

- A61K 31/5377: not condensed and containing further heterocyclic rings, e.g. timolol
- A61K 31/519: ortho- or peri-condensed with heterocyclic rings
- A61K 33/14: Alkali metal chlorides; Alkaline earth metal chlorides
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61K 51/02: characterised by the carrier {, i.e. characterised by the agent or material covalently linked or complexing the radioactive nucleus}
- A61P 35/00: Antineoplastic agents
- A61P 35/04: specific for metastasis
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- A61K 51/00: Preparations containing radioactive substances for use in therapy or testing in vivo
- A61K 51/04: Organic compounds
- 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 invention relates to combinations of at least two components, component A and component B, component A being an inhibitor of PI3K kinase, and component B being radium 223, particularly a pharmaceutically acceptable salt of radium-223. Another aspect of the present invention relates to the use of such combinations as described herein for the preparation of a medicament for the treatment or prophylaxis of a disease, particularly for the treatment of breast and prostate cancer as well as their bone metatases.

## Claims

### Claim 1

A pharmaceutical combination comprising:
component A, which is 2-amino-N-[7-methoxy-8-(3-morpholin-4-ylpropoxy)-2,3-dihydroimidazo[1,2-c]quinazolin-5-yl]pyrimidine-5-carboxamide,
or a physiologically acceptable salt, solvate, hydrate or stereoisomer thereof; and
component B, which is radium-223 dichloride.

### Claim 2 (depends on 1)

The pharmaceutical combination according to claim 1, wherein component A is
2-amino-N-[7-methoxy-8-(3-morpholin-4-ylpropoxy)-2,3-dihydroimidazo[1,2-c]quinazolin-5-yl]pyrimidine-5-carboxamide,
or a physiologically acceptable salt thereof.

### Claim 3 (depends on 1)

The pharmaceutical combination according to claim 1, wherein component A is
2-amino-N-[7-methoxy-8-(3-morpholin-4-ylpropoxy)-2,3-dihydroimidazo[1,2-c]quinazolin-5-yl]pyrimidine-5-carboxamide dihydrochloride.

### Claim 4 (depends on 1)

The pharmaceutical combination according to claim 1, wherein component A is
2-amino-N-[7-methoxy-8-(3-morpholin-4-ylpropoxy)-2,3-dihydroimidazo[1,2-c]quinazolin-5-yl]pyrimidine-5-carboxamide.

### Claim 5 (depends on 1)

A method for treatment of hepatocyte carcinoma, lung cancer, non-small cell lung carcinoma, colorectal cancer, melanoma, pancreatic cancer, prostate cancer, breast cancer or metastases thereof, comprising administering to a patient in need thereof a therapeutically effective amount of the pharmaceutical combination according to claim 1.

### Claim 6 (depends on 1)

A kit comprising the pharmaceutical combination according to claim 1, and optionally one or more further pharmaceutical agents C,
wherein optionally both or either of components A and B are in the form of a pharmaceutical formulation which is ready for use to be administered simultaneously, concurrently, separately or sequentially.

### Claim 7 (depends on 1)

A pharmaceutical composition comprising the pharmaceutical combination according to claim 1 and a pharmaceutically acceptable ingredient.

### Claim 8 (depends on 1)

A method for treatment of multiple myeloma, lung cancer, breast cancer, prostate cancer, or metastases thereof, comprising administering to a patient in need thereof a therapeutically effective amount of the pharmaceutical combination according to claim 1.

### Claim 9 (depends on 5)

The method according to claim 5, wherein the metastases are bone metastases.

### Claim 10 (depends on 8)

The method of claim 8, wherein the prostate cancer is castration-resistant prostate cancer (CRPC).

### Claim 11 (depends on 5)

The method of claim 5, wherein the pharmaceutical combination comprises
2-amino-N-[7-methoxy-8-(3-morpholin-4-ylpropoxy)-2,3-dihydroimidazo[1,2-c]quinazolin-5-yl]pyrimidine-5-carboxamide
or a physiologically acceptable salt thereof.

### Claim 12 (depends on 6)

The kit of claim 6, wherein the pharmaceutical combination comprises
2-amino-N-[7-methoxy-8-(3-morpholin-4-ylpropoxy)-2,3-dihydroimidazo[1,2-c]quinazolin-5-yl]pyrimidine-5-carboxamide
or a physiologically acceptable salt thereof.

### Claim 13 (depends on 7)

The pharmaceutical composition of claim 7, wherein the pharmaceutical combination comprises
2-amino-N-[7-methoxy-8-(3-morpholin-4-ylpropoxy)-2,3-dihydroimidazo[1,2-c]quinazolin-5-yl]pyrimidine-5-carboxamide
or a physiologically acceptable salt thereof.

### Claim 14 (depends on 8)

The method of claim 8, wherein the pharmaceutical combination comprises
2-amino-N-[7-methoxy-8-(3-morpholin-4-ylpropoxy)-2,3-dihydroimidazo[1,2-c]quinazolin-5-yl]pyrimidine-5-carboxamide
or a physiologically acceptable salt thereof.