G1 Therapeutics, Inc.

Gi Therapeutics, Inc.

The University of North Carolina at Chapel Hill

Harvard College

The Brigham and Women's Hospital, Inc.

Pharmacosmos Holding A/s

Patrick Joseph Roberts

Jay Copeland Strum

John Emerson Bisi

Francis Xavier Tavares

Jessica A Sorrentino

Robert C Gadwood

Hannah S White

Norman E Sharpless

Ricky D Gaston

Kwok-kin Wong

Benjamin D Humphreys

John E Bisi

Kwok-Kin Wong

Soren Johnson

Yan Liu

Anne Y Lai

Derek P DiRocco

This invention is in the area of improved therapeutic combinations for and methods of treating selected retinoblastoma (Rb)-negative cancers and Rb-negative abnormal cellular proliferative disorders using particular topoisomerase inhibitors and specific cyclin-dependent kinase 4/6 (CDK4/6) inhibitors. In one aspect, the improved treatment of select Rb-negative cancers is disclosed using specific compounds disclosed herein in combination with a topoisomerase I inhibitor.

Treatment of Rb-negative tumors using topoisomerase inhibitors in combination with cyclin dependent kinase 4/6 inhibitors

This invention is in the area of improved compounds, compositions and methods of transiently protecting healthy cells, and in particular hematopoietic stem and progenitor cells (HSPC) as well as renal cells, from damage associated with DNA damaging chemotherapeutic agents. In one aspect, improved protection of healthy cells is disclosed using disclosed compounds that act as highly selective and short, transiently-acting cyclin-dependent kinase 4/6 (CDK 4/6) inhibitors when administered to subjects undergoing DNA damaging chemotherapeutic regimens for the treatment of proliferative disorders.

Transient protection of normal cells during chemotherapy

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.

HSPC-sparing treatments for RB-positive abnormal cellular proliferation

The addition of a selective, fast-acting, short half-life CDK 4/6 inhibitor in a very specific dosage regimen to the combination of chemotherapy with a checkpoint inhibitor provides superior results in the treatment of a tumor or cancer. The unexpected discovery is that the short pulsatile specifically-timed administration of a selective, fast-acting, short half-life CDK 4/6 inhibitor during administration of the chemotherapy portion of the triple combination therapy has a profound effect on the immune cells in the cancer microenvironment.

Preservation of immune response during chemotherapy regimens

This invention directed to methods for treating select RB-positive cancers and other Rb-positive abnormal cellular proliferative disorders using CDK4/6 inhibitors in specific dosing and combination or alternation regimes. In one aspect, treatments of select RB-positive cancers are disclosed using specific CDK4/6 inhibitors in combination or alternation with a Bruton's tyrosine kinase (BTK) inhibitor.

Anti-neoplastic combinations and dosing regimens using CDK4/6 inhibitor compounds to treat Rb-positive tumors

This invention is in the area of improved compounds and methods for treating selected cancers and hyperproliferative disorders.

Highly active anti-neoplastic and anti-proliferative agents

HSPC-sparing treatments for Rb-positive abnormal cellular proliferation

Treatment of Rb-negative tumors using topoisomerase with cyclin dependent kinase 4/6 inhibitors

This invention is in the area of tricyclic lactam 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, treatment of select Rb-positive cancers is disclosed using specific compounds disclosed herein. In certain embodiments, the compounds described herein act as selective cyclin-dependent kinase 4/6 (CDK 4/6) inhibitors when administered to subjects.

Tricyclic lactams for use in HSPC-sparing treatments for Rb-positive abnormal cellular proliferation

This invention directed to methods for treating select RB-positive cancers and other Rb-positive abnormal cellular proliferative disorders using CDK4/6 inhibitors in specific dosing and combination or alternation regimes. In one aspect, treatments of select RB-positive cancers are disclosed using specific CDK4/6 inhibitors in combination or alternation with another chemotherapeutic, for example, an additional kinase inhibitor, PD-1 inhibitor, or BCL-2 inhibitor, or combination thereof.

Anti-neoplastic combinations and dosing regimens using CDK4/6 inhibitor compounds to treat RB-positive tumors

Growing community of inventors

Durham, NC, United States of America

Patrick Joseph Roberts