Patents by Inventor Thomas H. Graham

Thomas H. Graham has filed for patents to protect the following inventions. This listing includes patent applications that are pending as well as patents that have already been granted by the United States Patent and Trademark Office (USPTO).

  • Publication number: 20240083913
    Abstract: The disclosure provides compounds of Formula (I) or a pharmaceutically acceptable salt thereof, wherein W1, W2, Y, Z, M, L, CY, Cz, R1, R2, R3, R4, R2a, Ry, Rz, and the subscripts m, n, q, and r are as described herein. The compounds or their pharmaceutically acceptable salts can inhibit the G12C mutant of Kirsten rat sarcoma (KRAS) protein and are expected to have utility as therapeutic agents, for example, for treating cancer. The disclosure also provides pharmaceutical compositions which comprise compounds of Formula (I) or pharmaceutically acceptable salts thereof. The disclosure also relates to methods for use of the compounds or their pharmaceutically acceptable salts in the therapy and prophylaxis of cancer and for preparing pharmaceuticals for this purpose.
    Type: Application
    Filed: May 3, 2023
    Publication date: March 14, 2024
    Inventors: Indu Bharathan, Symon Gathiaka, Yongxin Han, Xiaoshen Ma, Ryan D. Otte, David L. Sloman, Thomas H. Graham, Timothy Henderson, Elisabeth Hennessy, Anandan Palani
  • Publication number: 20240076297
    Abstract: The present invention provides compounds of the structural Formula (I), and pharmaceutically acceptable salts thereof, wherein, are as defined herein, pharmaceutical compositions comprising one or more such compounds (alone and in combination with one or more other therapeutically active agents), and methods for their preparation and use, alone and in combination with other therapeutic agents, as antagonists of A2a and/or A2b receptors, and in the treatment of a variety of diseases, conditions, or disorders that are mediated, at least in part, by the adenosine A2a receptor and/or the adenosine A2b receptor.
    Type: Application
    Filed: July 22, 2021
    Publication date: March 7, 2024
    Applicant: Merck Sharp & Dohme LLC
    Inventors: Amjad Ali, Jared N. Cumming, Manuel De Lera Ruiz, Duane DeMong, Thomas H. Graham, Elisabeth T. Hennessy, Joseph M. Kelly, Rongze Kuang, Michael Man-Chu Lo, Umar Faruk Mansoor, Jesus Moreno, Uma Swaminathan, Heping Wu, Yingchun Ye, Younong Yu
  • Publication number: 20240043448
    Abstract: The disclosure provides compounds of Formula (I) or a pharmaceutically acceptable salt thereof, wherein W1, W2, Y, Z, M, L, Cy, Cz, R1, R2, R3, R4, R2a, Ry, Rz, and the subscripts m, n, q, and r are as described herein. The compounds or their pharmaceutically acceptable salts can inhibit the G12C mutant of Kirsten rat sarcoma (KRAS) protein and are expected to have utility as therapeutic agents, for example, for treating cancer. The disclosure also provides pharmaceutical compositions which comprise compounds of Formula (I) or pharmaceutically acceptable salts thereof. The disclosure also relates to methods for use of the compounds or their pharmaceutically acceptable salts in the therapy and prophylaxis of cancer and for preparing pharmaceuticals for this purpose.
    Type: Application
    Filed: May 3, 2023
    Publication date: February 8, 2024
    Inventors: Indu Bharathan, Symon Gathiaka, Yongxin Han, Xiaoshen Ma, Ryan D. Otte, David L. Sloman, Thomas H. Graham, Timothy Henderson, Elisabeth Hennessy, Anandan Palani
  • Publication number: 20230322785
    Abstract: The present invention provides compounds of the structural Formula (I) and pharmaceutically acceptable salts thereof, wherein, are as defined herein, pharmaceutical compositions comprising one or more such compounds (alone and in combination with one or more other therapeutically active agents), and methods for their preparation and use, alone and in combination with other therapeutic agents, as antagonists of A2a and/or A2b receptors, and in the treatment of a variety of diseases, conditions, or disorders that are mediated, at least in part, by the adenosine A2a receptor and/or the adenosine A2b receptor.
    Type: Application
    Filed: July 21, 2022
    Publication date: October 12, 2023
    Applicant: Merck Sharp & Dohme LLC
    Inventors: Amjad Ali, Christopher W. Boyce, Jared N. Cumming, Duane DeMong, Thomas H. Graham, Subrahmanyam Gudipati, Andrew J. Hoover, Xianhai Huang, Rongze Kuang, Jae-Hun Kim, Joseph M. Kelly, Yeon-Hee Lim, Michael Man-Chu Lo, Jesus Moreno, Jing Su, Heping Wu, Dong Xiao, Younong Yu, Xiaohong Zhu
  • Patent number: 11697657
    Abstract: The disclosure provides compounds of Formula (I) or a pharmaceutically acceptable salt thereof, wherein W1, W2, Y, Z, M, L, Cy, Cz, R1, R2, R3, R4, R2a, Ry, Rz and the subscripts m, n, q, and r are as described herein. The compounds or their pharmaceutically acceptable salts can inhibit the G12C mutant of Kirsten rat sarcoma (KRAS) protein and are expected to have utility as therapeutic agents, for example, for treating cancer. The disclosure also provides pharmaceutical compositions which comprise compounds of Formula (I) or pharmaceutically acceptable salts thereof. The disclosure also relates to methods for use of the compounds or their pharmaceutically acceptable salts in the therapy and prophylaxis of cancer and for preparing pharmaceuticals for this purpose.
    Type: Grant
    Filed: October 27, 2020
    Date of Patent: July 11, 2023
    Assignee: Merck Sharp & Dohme LLC
    Inventors: Indu Bharathan, Symon Gathiaka, Yongxin Han, Xiaoshen Ma, Ryan D. Otte, David L. Sloman, Thomas H. Graham, Timothy Henderson, Elisabeth Hennessy, Anandan Palani
  • Publication number: 20230054411
    Abstract: In its many embodiments, the present invention provides certain 7-, 8-, and 10-substituted amino triazolo quinazoline derivatives of Formula (I): or a pharmaceutically acceptable salt thereof, wherein ring A, R1, R2, and R4 are as defined herein, pharmaceutical compositions comprising one or more such compounds (alone and in combination with one or more other therapeutic agents), and methods for their preparation and use, alone and in combination with other therapeutic agents, as antagonists of A2a and/or A2b receptors, and their use in the treatment of a variety of diseases, conditions, or disorders that are mediated, at least in part, by the adenosine A2a receptor and/or the adenosine A2b receptor.
    Type: Application
    Filed: November 26, 2019
    Publication date: February 23, 2023
    Applicant: Merck Sharp & Dohme Corp.
    Inventors: Yonglian Zhang, Amjad Ali, Jared Cumming, Duane DeMong, Qiaolin Deng, Thomas H. Graham, Elisabeth Hennessy, Matthew A. Larsen, Kun Liu, Ping Liu, Umar Faruk Mansoor, Jianping Pan, Christopher W. Plummer, Aaron Sather, Uma Swaminathan, Huijun Wang
  • Publication number: 20220402916
    Abstract: Provided are compounds of Formula (I) or a pharmaceutically acceptable salt thereof, wherein Y, CY, R1, R3, R4, R5, R6, R2a, R2b, RMa, RMb, and the subscripts m, n, and q are as described herein. The compounds or their pharmaceutically acceptable salts can inhibit the G12C mutant of Kirsten rat sarcoma (KRAS) protein and are expected to have utility as therapeutic agents, for example, for treatment of cancer. Also provided are pharmaceutical compositions which comprise compounds of Formula (I) or pharmaceutically acceptable salts thereof. Also provided are methods for use of the compounds or their pharmaceutically acceptable salts in the therapy and prophylaxis of cancer and for preparing pharmaceuticals for this purpose.
    Type: Application
    Filed: September 18, 2020
    Publication date: December 22, 2022
    Inventors: Andrew J. Hoover, Thomas H. Graham, Xiaoshen Ma, Zahid Hussain, Mihir Mandal, Symon Gathiaka, Yongxin Han, David L. Sloman
  • Publication number: 20220220117
    Abstract: In its many embodiments, the present invention provides certain 9-substituted amino triazolo quinazoline compounds of the structural Formula (I): and pharmaceutically acceptable salts thereof, wherein, ring A, R1 and R2 are as defined herein, pharmaceutical compositions comprising one or more such compounds (alone and in combination with one or more other therapeutically active agents), and methods for their preparation and use, alone and in combination with other therapeutic agents, as antagonists of A2a and/or A2b receptors, and in the treatment of a variety of diseases, conditions, or disorders that are mediated, at least in part, by the adenosine A2a receptor and/or the adenosine A2b receptor.
    Type: Application
    Filed: March 31, 2022
    Publication date: July 14, 2022
    Applicant: Merck Sharp & Dohme Corp.
    Inventors: Matthew A. Larsen, Amjad Ali, Jared Cumming, Duane DeMong, Qiaolin Deng, Thomas H. Graham, Elisabeth Hennessy, Andrew J. Hoover, Ping Liu, Kun Liu, Umar Faruk Mansoor, Jianping Pan, Christopher W. Plummer, Aaron Sather, Uma Swaminathan, Huijun Wang, Yonglian Zhang
  • Patent number: 11358711
    Abstract: The present invention relates to Tetracyclic Heterocycle Compounds of Formula and pharmaceutically acceptable salts or prodrug thereof, wherein A, X, R1, R2, R3 and Ware as defined herein. The present invention also relates to compositions comprising at least one Tetracyclic Heterocycle Compound, and methods of using the Tetracyclic Heterocycle Compounds for treating or preventing HIV infection in a subject.
    Type: Grant
    Filed: September 18, 2020
    Date of Patent: June 14, 2022
    Assignee: Merck Sharp & Dohme Corp.
    Inventors: Thomas H. Graham, Tao Yu, Yonglian Zhang, John A. McCauley
  • Patent number: 11312719
    Abstract: In its many embodiments, the present invention provides certain 9-substituted amino triazolo quinazoline compounds of the structural Formula (I): and pharmaceutically acceptable salts thereof, wherein, ring A, R1 and R2 are as defined herein, pharmaceutical compositions comprising one or more such compounds (alone and in combination with one or more other therapeutically active agents), and methods for their preparation and use, alone and in combination with other therapeutic agents, as antagonists of A2a and/or A2b receptors, and in the treatment of a variety of diseases, conditions, or disorders that are mediated, at least in part, by the adenosine A2a receptor and/or the adenosine A2b receptor.
    Type: Grant
    Filed: November 26, 2019
    Date of Patent: April 26, 2022
    Assignee: Merck Sharp & Dohme Corp.
    Inventors: Matthew A. Larsen, Amjad Ali, Jared Cumming, Duane DeMong, Qiaolin Deng, Thomas H. Graham, Elisabeth Hennessy, Andrew J. Hoover, Ping Liu, Kun Liu, Umar Faruk Mansoor, Jianping Pan, Christopher W. Plummer, Aaron Sather, Uma Swaminathan, Huijun Wang, Yonglian Zhang
  • Publication number: 20220040184
    Abstract: In its many embodiments, the present invention provides certain substituted amino triazolopyrimidine and amino triazolopyrazine compounds of Formula (IA) and Formula (IB): and, and pharmaceutically acceptable salts thereof, wherein, R1, n, R2, and R3 are as defined herein, pharmaceutical compositions comprising one or more such compounds (alone and in combination with one or more other therapeutically active agents), and methods for their preparation and use, alone and in combination with other therapeutic agents, as antagonists of A2a and/or A2b receptors, and their use in the treatment of a variety of diseases, conditions, or disorders that are mediated, at least in part, by the adenosine A2a receptor and/or the adenosine A2b receptor.
    Type: Application
    Filed: November 15, 2019
    Publication date: February 10, 2022
    Applicant: Merck Sharp Dohme Corp.
    Inventors: Zachary G. Brill, Amjad Ali, Jared Cumming, Duane DeMong, Qiaolin Deng, Gioconda V. Gallo-Etienne, Thomas H. Graham, Rongze Kuang, Matthew A. Larsen, Yeon-Hee Lim, Kun Liu, Umar Faruk Mansoor, Jesus Moreno, Brandon A. Vara, Huijun Wang, Yonglian Zhang
  • Publication number: 20210395255
    Abstract: In its many embodiments, the present invention provides certain substituted amino triazolopyrimidine and amino triazolopyrazine compounds of Formula (IA) and Formula (IB): or and pharmaceutically acceptable salts thereof, wherein, R1, R2, and R3 are as defined herein, pharmaceutical compositions comprising one or more such compounds (alone and in combination with one or more other therapeutically active agents), and methods for their preparation and use, alone and in combination with other therapeutic agents, as antagonists of A2a and/or A2b receptors, and their use in the treatment of a variety of diseases, conditions, or disorders that are mediated, at least in part, by the adenosine A2a receptor and/or the adenosine A2b receptor.
    Type: Application
    Filed: November 15, 2019
    Publication date: December 23, 2021
    Applicant: Merck Sharp & Dohme Corp.
    Inventors: Zachary G. Brill, Amjad Ali, Jared Cumming, Duane DeMong, Qiaolin Deng, Thomas H. Graham, Rongze Kuang, Yeon-Hee Lim, Christopher W. Plummer, Jenny Lorena Rico Duque, Huijun Wang, Yonglian Zhang, Kake Zhao
  • Patent number: 11161854
    Abstract: The present invention is directed to substituted certain reversed indazolyl-spiro[2.2]pentane-carbonitrile derivatives of Formula (I): and pharmaceutically acceptable salts thereof, wherein R1, R2, R3, X, Y, and Z are as defined herein, which are potent inhibitors of LRRK2 kinase and may be useful in the treatment or prevention of diseases in which the LRRK2 kinase is involved, such as Parkinson's Disease and other diseases and disorders described herein. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which LRRK-2 kinase is involved.
    Type: Grant
    Filed: October 8, 2018
    Date of Patent: November 2, 2021
    Assignee: Merck Sharp & Dohme Corp.
    Inventors: David Annunziato Candito, Thomas H. Graham, John Acton, Ryan Wing-Kun Chau, Joanna L. Chen, J. Michael Ellis, Peter H. Fuller, Anmol Gulati, Hakan Gunaydin, Solomon Kattar, Mitchell Henry Keylor, Blair T. Lapointe, Ping Liu, Weiguo Liu, Joey L. Methot, Santhosh F. Neelamkavil, Vladimir Simov, Ling Tong, Harold B. Wood
  • Patent number: 11104690
    Abstract: The present invention relates to a compound represented by formula I?: and pharmaceutically acceptable salts thereof. The compounds of formula I are inhibitors of diacylglyceride O-acyltransferase 2 (“DGAT2”) and may be useful in the treatment, prevention and suppression of diseases mediated by DGAT2. The compounds of the present invention may be useful in the treatment of hepatic steatosis, diabetes mellitus, obesity, hyperlipidemia, hypercholesterolemia, atherosclerosis, cardiorenal diseases such as chronic kidney diseases and heart failure and related diseases and conditions.
    Type: Grant
    Filed: November 13, 2017
    Date of Patent: August 31, 2021
    Assignee: Merck Sharp & Dohme Corp.
    Inventors: Dong-Ming Shen, Thomas H. Graham, Wensheng Liu, Clare Tudge, Andreas Verras, Jinlong Jiang
  • Publication number: 20210188863
    Abstract: The present invention is directed to substituted certain reversed indazolyl-spiro[2.2]pentane-carbonitrile derivatives of Formula (I): and pharmaceutically acceptable salts thereof, wherein R1, R2, R3, X, Y, and Z are as defined herein, which are potent inhibitors of LRRK2 kinase and may be useful in the treatment or prevention of diseases in which the LRRK2 kinase is involved, such as Parkinson's Disease and other diseases and disorders described herein. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which LRRK-2 kinase is involved.
    Type: Application
    Filed: October 8, 2018
    Publication date: June 24, 2021
    Applicant: Merck Sharp & Dohme Corp.
    Inventors: David Annunziato Candito, Thomas H. Graham, John Acton, Ryan Wing-Kun Chau, Joanna L. Chen, J. Michael Ellis, Peter H. Fuller, Anmol Gulati, Hakan Gunaydin, Solomon Kattar, Mitchell Henry Keylor, Blair T. Lapointe, Ping Liu, Weiguo Liu, Joey L. Methot, Santhosh F. Neelamkavil, Vladimir Simov, Ling Tong, Harold B. Wood
  • Publication number: 20210122764
    Abstract: The disclosure provides compounds of Formula (I) or a pharmaceutically acceptable salt thereof, wherein W1, W2, Y, Z, M, L, Cy, Cz, R1, R2, R3, R4, R2a, Ry, Rz and the subscripts m, n, q, and r are as described herein. The compounds or their pharmaceutically acceptable salts can inhibit the G12C mutant of Kirsten rat sarcoma (KRAS) protein and are expected to have utility as therapeutic agents, for example, for treating cancer. The disclosure also provides pharmaceutical compositions which comprise compounds of Formula (I) or pharmaceutically acceptable salts thereof. The disclosure also relates to methods for use of the compounds or their pharmaceutically acceptable salts in the therapy and prophylaxis of cancer and for preparing pharmaceuticals for this purpose.
    Type: Application
    Filed: October 27, 2020
    Publication date: April 29, 2021
    Inventors: Indu Bharathan, Symon Gathiaka, Yongxin Han, Xiaoshen Ma, Ryan D. Otte, David L. Sloman, Thomas H. Graham, Timothy Henderson, Elizabeth Hennessy, Anandan Palani
  • Publication number: 20210107904
    Abstract: In its many embodiments, the present invention provides certain 9-substituted amino triazolo quinazoline compounds of the structural Formula (I): and pharmaceutically acceptable salts thereof, wherein, ring A, R1 and R2 are as defined herein, pharmaceutical compositions comprising one or more such compounds (alone and in combination with one or more other therapeutically active agents), and methods for their preparation and use, alone and in combination with other therapeutic agents, as antagonists of A2a and/or A2b receptors, and in the treatment of a variety of diseases, conditions, or disorders that are mediated, at least in part, by the adenosine A2a receptor and/or the adenosine A2b receptor.
    Type: Application
    Filed: November 26, 2019
    Publication date: April 15, 2021
    Applicant: Merck Sharp & Dohme Corp.
    Inventors: Matthew A. Larsen, Amjad Ali, Jared Cumming, Duane DeMong, Qiaolin Deng, Thomas H. Graham, Elisabeth Hennessy, Andrew J. Hoover, Ping Liu, Kun Liu, Umar Faruk Mansoor, Jianping Pan, Christopher W. Plummer, Aaron Sather, Uma Swaminathan, Huijun Wang, Yonglian Zhang
  • Patent number: 10947222
    Abstract: The present invention relates to a compound represented by formula I: and pharmaceutically acceptable salts thereof. The compounds of formula I are inhibitors of diacylglyceride O-acyltransferase 2 (“DGAT2”) and may be useful in the treatment, prevention and suppression of diseases mediated by DGAT2. The compounds of the present invention may be useful in the treatment of hepatic steatosis, diabetes mellitus, obesity, hyperlipidemia, hypercholesterolemia, atherosclerosis, nonalcoholic steatohepatitis (NASH), cardiorenal diseases such as chronic kidney diseases and heart failure and related diseases and conditions.
    Type: Grant
    Filed: November 13, 2017
    Date of Patent: March 16, 2021
    Assignee: Merck Sharp & Dohme Corp.
    Inventors: Dong-Ming Shen, Thomas H. Graham, Jinlong Jiang, Fa-Xiang Ding, Clare Tudge
  • Patent number: 10934312
    Abstract: The present invention relates to Tricyclic Heterocycle Compounds of Formula (I): and pharmaceutically acceptable salts or prodrug thereof, wherein A, X, Y, Z, R1, R7A, R7B and R8 are as defined herein. The present invention also relates to compositions comprising at least one Tricyclic Heterocycle Compound, and methods of using the Tricyclic Heterocycle Compounds for treating or preventing HIV infection in a subject.
    Type: Grant
    Filed: December 1, 2017
    Date of Patent: March 2, 2021
    Assignee: MERCK SHARP & DOHME CORP.
    Inventors: Thomas H. Graham, Tao Yu, Sherman T. Waddell, John A. McCauley
  • Publication number: 20210040096
    Abstract: The present invention relates to Fused Tricyclic Heterocyclic Compounds of Formula (I): and pharmaceutically acceptable salts thereof, wherein R1, R2 and R3 are as defined herein. The present invention also relates to compositions comprising at least one Fused Tricyclic Heterocyclic Compound, and methods of using the Fused Tricyclic Heterocyclic Compounds for treating or preventing HIV infection in a subject.
    Type: Application
    Filed: October 27, 2020
    Publication date: February 11, 2021
    Applicant: Merck Sharp & Dohme Corp.
    Inventors: Tao Yu, Sherman T. Waddell, Thomas H. Graham, Yonglian Zhang, John A. McCauley, Andrew W. Stamford, Jiaqiang Cai, Zhiqi Qi