Abstract: Compositions, combinations and methods comprising a CDK4/6 inhibitor of Formula D with a selective estrogen receptor downregulator of Formula A, B or C that are advantageous for the treatment of abnormal cellular proliferation, including a cancer or a tumor.
Type:
Grant
Filed:
July 2, 2019
Date of Patent:
June 21, 2022
Assignee:
G1 Therapeutics, Inc.
Inventors:
Jay C. Strum, Gregory R. Thatcher, Rui Xiong, Jiong Zhao, Debra A. Tonetti
Abstract: A G1T38 human oral dosage regime that provides a (mean AUC(0-24),ss (h*ng/mL))/(dose (mg)) ratio of less than 5 and/or a (mean AUC(0-24),ss (h*ng/mL))/(Absolute Neutrophil Count (cells/mm3)) ratio on day 22 of dosing of not greater than 1.25.
Abstract: A method for increasing the progression free survival or overall survival of a patient with cancer comprising: determining if the cancer has a surrounding microenvironment that is favorable to immune modulation; determining if the chemotherapy regimen induces immunogenic cell death, and if both are yes, administering an effective amount of a CDK 4/6 inhibitor selected from Compounds I, II, III, IV, or V, or a pharmaceutically acceptable salt thereof, wherein the CDK4/6 inhibitor is administered prior to the administration of the chemotherapy or optionally prior to and concurrently with chemotherapy; and, wherein the increase in progression free survival or overall survival is in comparison to the progression free survival or overall survival based on administration of the chemotherapy alone, either based on literature or otherwise publicly available evidence, a comparative during preclinical or clinical trials, or other means accepted by persons skilled in the field.
Type:
Application
Filed:
December 17, 2021
Publication date:
June 9, 2022
Applicant:
G1 Therapeutics Inc.
Inventors:
Patrick Joseph Roberts, Anne Lai, Jessica Sorrentino
Abstract: An advantageous isolated morphic form of trilaciclib which is 2?-((5-(4-methylpiperazin-1-yl)pyridin-2-yl)amino)-7?,8?-dihydro-6?H-spiro[cyclohexane-1,9?-pyrazino[1?,2?:1, 5]pyrrolo[2,3 -d]pyrimidin]-6?-one, for example in the form of a di-hydrochloride salt or a dihydrochloride, dihydrate.
Type:
Application
Filed:
April 21, 2021
Publication date:
December 16, 2021
Applicant:
G1 Therapeutics, Inc.
Inventors:
Stephen Schneider, Alexander Smith, Hannah S. White, Jay Copeland Strum, Jaroslaw Mazurek
Abstract: 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.
Type:
Application
Filed:
April 5, 2021
Publication date:
September 30, 2021
Applicant:
G1 Therapeutics, Inc.
Inventors:
Jay Copeland Strum, John Emerson Bisi, Patrick Joseph Roberts, Francis Xavier Tavares
Abstract: The present invention provides methods and compositions for treating cancers with a combination of eribulin and a selective CDK4/6 inhibitor, wherein the selective CDK4/6 inhibitor reduces eribulin's effects on myelosuppression and/or myeloablation without reducing the efficacy of eribulin therapy.
Type:
Application
Filed:
May 7, 2021
Publication date:
September 2, 2021
Applicant:
G1 Therapeutics, Inc.
Inventors:
Jessica A. Sorrentino, Patrick Joseph Roberts, Jay Copeland Strum
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.
Type:
Application
Filed:
February 22, 2021
Publication date:
July 15, 2021
Applicant:
G1 Therapeutics, Inc.
Inventors:
Jay Copeland Strum, John Emerson Bisi, Patrick Joseph Roberts, Francis X. Tavares
Abstract: 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.
Type:
Grant
Filed:
May 28, 2020
Date of Patent:
June 22, 2021
Assignee:
G1 Therapeutics, Inc.
Inventors:
Jay Copeland Strum, John Emerson Bisi, Patrick Joseph Roberts, Francis Xavier Tavares
Abstract: This invention provides a process for preparing 1,4-diazaspiro[5.5]undecan-3-one and analogues thereof that are useful in the preparation of pharmaceutical compound, including for the treatment of disorders involving abnormal cellular proliferation. Chemical intermediates in the process are also provided.
Type:
Application
Filed:
February 24, 2021
Publication date:
June 17, 2021
Applicant:
G1 Therapeutics, Inc.
Inventors:
Stephen E. Schneider, Hannah White, Thomas Fessard, Sagar Beldar
Abstract: This invention is a benzothiophene estrogen receptor modulator or its pharmaceutically acceptable salt, N-oxide, isotopic derivative, or prodrug thereof or a pharmaceutically acceptable composition thereof to treat an estrogen-related medical disorder. The invention also includes a combination thereof with another active agent such as a CDK inhibitor, including a CDK4/6 inhibitor, to treat a disorder mediated by the estrogen receptor, as described in more detail herein.
Abstract: This invention is in the area of synthesizing pyrimidine-based compounds useful in the treatment of disorders involving abnormal cellular proliferation, including but not limited to tumors and cancers.
Type:
Application
Filed:
December 14, 2020
Publication date:
April 29, 2021
Applicant:
G1 Therapeutics, Inc.
Inventors:
Alexander Smith, Hannah S. White, Francis Xavier Tavares, Sergiy Krasutsky, Jian-Xie Chen, Roberta L. Dorrow, Hua Zhong
Abstract: An advantageous isolated morphic form of trilaciclib which is 2?-((5-(4-methylpiperazin-1-yl)pyridin-2-yl)amino)-7?,8?-dihydro-6?H-spiro[cyclohexane-1,9?-pyrazino[1?,2?:1,5]pyrrolo[2,3-d]pyrimidin]-6?-one, for example in the form of a di-hydrochloride salt or a dihydrochloride, dihydrate.
Type:
Grant
Filed:
November 13, 2020
Date of Patent:
April 27, 2021
Assignee:
G1 Therapeutics, Inc.
Inventors:
Stephen Schneider, Alexander Smith, Hannah S. White, Jay Copeland Strum, Jaroslaw Mazurek
Abstract: This invention is a benzothiophene estrogen receptor modulator or its pharmaceutically acceptable salt or a pharmaceutically acceptable composition thereof to treat an estrogen-related medical disorder.
Abstract: 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.
Type:
Grant
Filed:
August 24, 2018
Date of Patent:
April 6, 2021
Assignee:
G1 Therapeutics, Inc.
Inventors:
Jay Copeland Strum, John Emerson Bisi, Patrick Joseph Roberts, Francis Xavier Tavares
Abstract: This invention is in the area of improved compounds and methods for transiently protecting healthy cells, and in particular hematopoietic stem and progenitor cells (HSPC), from the damage associated with ionizing radiation (IR) exposure using selective radioprotectants.
Type:
Application
Filed:
November 23, 2020
Publication date:
March 18, 2021
Applicant:
G1 Therapeutics, Inc.
Inventors:
Jay Copeland Strum, John Emerson Bisi, Patrick Joseph Roberts, Francis Xavier Tavares
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.
Type:
Grant
Filed:
November 1, 2018
Date of Patent:
February 23, 2021
Assignee:
G1 Therapeutics, Inc.
Inventors:
Jay Copeland Strum, John Emerson Bisi, Patrick Joseph Roberts, Francis Xavier Tavares
Abstract: This invention is in the area of pyrimidine-based compounds for the treatment of disorders involving abnormal cellular proliferation, including but not limited to tumors and cancers.
Abstract: Methods and compositions are described to treat a cancer having a specific oncogenic driving mutation by administering a CDK4/6 inhibitor in combination with an additional kinase inhibitor, wherein the specific combination provides advantageous or synergistic inhibitory activity, delays acquired resistance to the additional kinase inhibitor, and/or extends the efficacy of the kinase inhibitor.
Type:
Application
Filed:
October 9, 2020
Publication date:
February 4, 2021
Applicant:
G1 Therapeutics, Inc.
Inventors:
Jay Copeland Strum, Daniel M. Freed, Jessica A. Sorrentino, John E. Bisi, Andrew Beelen, Patrick Joseph Roberts
Abstract: A G1T38 human oral dosage regime that provides a (mean AUC(0-24),ss (h*ng/mL))/(dose (mg)) ratio of less than 5 and/or a (mean AUC(0-24),ss (h*ng/mL))/(Absolute Neutrophil Count (cells/mm3)) ratio on day 22 of dosing of not greater than 1.25.