# US 11,439,625 B2 · Combination therapy for proliferative diseases

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- Number: US 11,439,625 B2
- Document ID: US11439625B2
- Status: Granted
- Kind: B2
- Application number: 16/084,832
- Filed: 2017-03-14
- Published: 2019-03-14
- Granted: 2022-09-13
- Earliest claimed: 2016-03-14
- Assignees: Avexxin AS
- Applicants: Avexxin AS
- Inventors: Berit Johansen; Astrid Jullumstrø Feuerherm
- Web page: https://patentgrep.com/patent/US11439625B2

## CPC

- A61K 31/426: 1,3-Thiazoles
- A61K 9/0019: {Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner (non-active ingredients are additionally classified in A61K47/00)}
- A61K 31/4745: condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenantrolines (yohimbine derivatives, vinblastine A61K31/475; ergoline derivatives A61K31/48)
- 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

A combination product comprising: (A) a compound of formula (I) (I) wherein X is O or S, preferably O; R6 is H, C1-6alkyl, —(CH2)pCOOH, —(CH2)pCOOC1-6alkyl, —(CH2)pCONH2, (CH2)pCONHC1-6alkyl, and —(CH2)pCON(C1-6alkyl)2; R11 is H or C1-6 alkyl; each R5 is —OC1-10alkyl, —SC1-10alkyl, —C1-12alkyl, or OAr2; wherein Ar2 is phenyl, optionally substituted with one or more halo; each p is 0 to 3; each z is 1 to 2; or a salt thereof; and (B) a compound of formula (X) (X) where R1 is phenyl wherein said phenyl is substituted by lower alkyl unsubstituted or substituted by cyano; R3 is lower alkyl, such as methyl; and R4 is quinolinyl unsubstituted or substituted by halogen; or a tautomer thereof, or a pharmaceutically acceptable salt, or a hydrate or solvate thereof.

## Claims

### Claim 1

A combination product comprising:
(A) Compound 1 or Compound 2 represented by one of the formulas below:
or a salt thereof; and
(B) BEZ235 represented by the formula below:
or a salt thereof.

### Claim 2

A pharmaceutical composition comprising:
(A) Compound 1 or Compound 2 represented by one of the formulas below:
or a salt thereof;
(B) BEZ235 represented by the formula below:
or a salt thereof; and
a pharmaceutically acceptable diluent or carrier.

### Claim 3 (depends on 1)

A pharmaceutical composition for simultaneous, sequential or separate use comprising a kit comprising a first composition comprising Compound 1 or Compound 2 as defined in claim 1 and a pharmaceutically-acceptable diluent or carrier, and a second composition comprising BEZ235 as defined in claim 1 and a pharmaceutically-acceptable diluent or carrier.

### Claim 4 (depends on 2)

The pharmaceutical composition of claim 2 wherein the pharmaceutical composition is a fixed combination or non-fixed combination.

### Claim 5 (depends on 2)

The pharmaceutical composition of claim 2, comprising (A) Compound 1, (B) BEZ235 or a salt thereof, and a pharmaceutically acceptable diluent or carrier.

### Claim 6 (depends on 2)

The pharmaceutical composition of claim 2, comprising (A) Compound 2, (B) BEZ235 or a salt thereof, and a pharmaceutically acceptable diluent or carrier.

### Claim 7 (depends on 2)

A method of treating cancer in a patient in need thereof comprising administering to said patient an effective amount of a pharmaceutical composition as claimed in claim 2, wherein the cancer is breast carcinoma.

### Claim 8 (depends on 2)

A method of treating cancer in a patient in need thereof comprising administering to said patient an effective amount of Compound 1 or Compound 2 as defined in claim 2 and simultaneously, separately or sequentially administering to said patient BEZ235 or a salt thereof as defined in claim 2, wherein the cancer is breast carcinoma.

### Claim 9 (depends on 2)

A method of treating cancer in a patient in need thereof comprising:
(i) identifying a patient who has received either one of Compound 1 and Compound 2, or BEZ235, as defined in claim 2 respectively;
(ii) administering to said patient an effective amount of either BEZ235, or one of Compound 1 and Compound 2, as defined in claim 2 so that said patient is administered with both Compound 1 and BEZ235, or both Compound 2 and BEZ235,
wherein the cancer is breast carcinoma.