HSPC-sparing treatments for RB-positive abnormal cellular proliferation

Patent metadata

Field	Value
Publication number	US-11654148-B2
Application number	US-202117181638-A
Country	US
Kind code	B2
Filing date	Feb 22, 2021
Priority date	Mar 15, 2013
Publication date	May 23, 2023
Grant date	May 23, 2023

Abstract

This invention is in the area of improved compounds for and methods of treating selected RB-positive cancers and other Rb-positive abnormal cellular proliferative disorders while minimizing the deleterious effects on healthy cells, for example healthy Hematopoietic Stem Cells and Progenitor Cells (HSPCs), associated with current treatment modalities. In one aspect, improved treatment of select RB-positive cancers is disclosed using specific compounds disclosed herein. In certain embodiments, the compounds described herein act as highly selective and, in certain embodiments, short, transiently-acting cyclin-dependent kinase 4/6 (CDK 4/6) inhibitors when administered to subjects.

First claim

We claim:

1. A method for treating retinoblastoma (Rb)-positive non-small cell lung cancer in a human comprising orally administering to the human an effective amount of a selective CDK4/6 inhibitor compound of structure

or a pharmaceutically acceptable salt thereof, wherein the compound is administered to the human at least once a day for 24 or more continuous days.

2. The method of claim 1 , wherein the compound is administered to the human at least once a day for 28 or more continuous days.

3. The method of claim 1 , wherein the compound is administered to the human at least once a day for 35 or more continuous days.

4. The method of claim 1 , wherein the compound is administered to the human twice a day.

5. The method of claim 2 , wherein the compound is administered to the human twice a day.

6. The method of claim 3 , wherein the compound is administered to the human twice a day.

7. The method of claim 1 , further comprising administering to the human at least one additional chemotherapeutic agent.

8. A method for treating progesterone-receptor positive breast cancer in a human comprising orally administering to the human an effective amount of a selective CDK4/6 inhibitor compound of structure

or a pharmaceutically acceptable salt thereof, wherein the compound is administered to the human twice a day for 24 or more continuous days.

9. The method of claim 8 , wherein the compound is administered to the human twice a day for 28 or more continuous days.

10. The method of claim 8 , wherein the compound is administered to the human twice a day for 35 or more continuous days.

11. The method of claim 8 , further comprising administering to the human at least one additional chemotherapeutic agent.

12. The method of claim 11 , wherein the additional chemotherapeutic agent is tamoxifen.

13. The method of claim 11 , wherein the additional chemotherapeutic agent is letrozole.

14. The method of claim 11 , wherein the additional chemotherapeutic agent is anastrozole.

15. The method of claim 11 , wherein the additional chemotherapeutic agent is toremifene.

16. The method of claim 11 , wherein the additional chemotherapeutic agent is goserelin.

Assignees

• G1 Therapeutics Inc

Inventors

• Strum Jay Copeland
• Bisi John Emerson
• Roberts Patrick Joseph
• Tavares Francis X

Classifications

• A61K31/7048

  having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin {, digitoxin or digoxin} · CPC title

• A61P35/04

  specific for metastasis · CPC title

• A61K45/06

  Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca · CPC title

• A61K31/527 Primary

  spiro-condensed · CPC title

• A61K31/555

  containing heavy metals, e.g. hemin, hematin, melarsoprol · CPC title