Combination treatment for acute myeloid leukemia (AML)

Patent metadata

Field	Value
Publication number	US-9956243-B2
Application number	US-201414560086-A
Country	US
Kind code	B2
Filing date	Dec 4, 2014
Priority date	Dec 5, 2013
Publication date	May 1, 2018
Grant date	May 1, 2018

Abstract

The present invention relates to a pharmaceutical product comprising a) as a first component an inhibitor of the MDM2-p53 interaction such as, for example:

and b) as a second component cytarabine; as a combined preparation for the sequential or simultaneous use in the treatment of cancer.

First claim

What is claimed:

1. A pharmaceutical product, comprising a) as a first component an inhibitor of the MDM2-p53 interaction; and b) as a second component cytarabine, wherein the inhibitor of the MDM2-p53 interaction is a compound of formula (I):

wherein n is from 3 to 70; or a compound of formula (A):

2. The pharmaceutical product according to claim 1 , wherein n is from 30 to 60.

3. A method for treating acute myeloid leukemia, said method comprising: administering to a patient in need thereof the product of claim 2 .

4. The pharmaceutical product according to claim 1 , wherein a is from 40 to 50.

5. A method for treating acute myeloid leukemia, said method comprising: administering to a patient in need thereof the product of claim 4 .

6. The pharmaceutical product according to claim 1 , wherein n is 41, 42, 43, 44, 46, 47, 48 or 49.

7. A method for treating acute myeloid leukemia, said method comprising: administering to a patient in need thereof the product of claim 6 .

8. The pharmaceutical product according to claim 1 , wherein the inhibitor of the MDM2-p53 interaction is 4-{[(2R,3S,4R,5S)-3-(3-chloro-2-fluoro-phenyl)-4-(4-chloro-2-fluoro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carbonyl]-amino}-3-methoxy-benzoic acid 1-mPEG-carbonyloxy-ethyl ester (mPEG, average MW, ˜2000); or wherein the inhibitor of the MDM2-p53 interaction is 4-{[(2R,3S,4R,5S)-3-(3-chloro-2-fluoro-phenyl)-4-(4-chloro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carbonyl]-amino}-3-methoxy-benzoic acid 1-mPEG-carbonyloxy-ethyl ester (mPEG, average MW, ˜2200); or combinations thereof.

9. A method for treating acute myeloid leukemia, said method comprising: administering to a patient in need thereof the product of claim 8 .

10. The pharmaceutical product according to claim 1 , wherein the inhibitor of the MDM2-p53 interaction is the compound of formula (A)

11. A method for treating acute myeloid leukemia, said method comprising: administering to a patient in need thereof the product of claim 1 .

12. A pharmaceutical product, comprising, a) as a first component a compound of formula (I):

wherein n is from 3 to 70; and b) as a second component the compound cytarabine, wherein the dose of the compound of formula (I) corresponds to a dose of compound (A):

within the range from about 200 to about 1600 mg/day.

13. The pharmaceutical product according to claim 12 , wherein the compound of formula (I) is the compound 4-{[(2R,3S,4R,5S)-3-(3-chloro-2-fluoro-phenyl)-4-(4-chloro-2-fluoro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carbonyl]-amino}-3-methoxy-benzoic acid 1-mPEG-carbonyloxy-ethyl ester (mPEG, average MW, ˜2000); or 4-{[(2R,3S,4R,5S)-3-(3-chloro-2-fluoro-phenyl)-4-(4-chloro-2-fluoro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carbonyl]-amino}-3-methoxy-benzoic acid 1-mPEG-carbonyloxy-ethyl ester (mPEG, average MW, ˜2200); or combinations thereof.

Assignees

• Hoffmann La Roche

Inventors

• Higgins Brian
• Nichols Gwen
• Packman Kathryn E

Classifications

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61P35/02

  specific for leukemia · CPC title

• A61K31/40 Primary

  having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil · CPC title

• A61K9/0019 Primary

  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) · CPC title