Abstract: The present invention relates generally to the use of gene mutations, whose presence or absence are useful for predicting a patient's response to treatment with an anti-proliferative agent, in particular a WEE1 inhibitor. The presence or absence of a mutation to the TP53 gene, can be used to predict response to treatment with a WEE1 inhibitor in a patient presenting with a cancerous condition.
Abstract: Novel compounds of the structural formula (I), and the pharmaceutically acceptable salts thereof, are agonists of G-protein coupled receptor 40 (GPR40) and may be useful in the treatment, prevention and suppression of diseases mediated by the G-protein-coupled receptor 40. The compounds of the present invention may be useful in the treatment of Type 2 diabetes mellitus, and of conditions that are often associated with this disease, including obesity and lipid disorders, such as mixed or diabetic dyslipidemia, hyperlipidemia, hypercholesterolemia, and hypertriglyceridemia.
Type:
Grant
Filed:
August 3, 2015
Date of Patent:
May 26, 2020
Assignee:
Merck Sharp & Dohme Corp.
Inventors:
Harry Chobanian, Duane DeMong, Yan Guo, Barbara Pio, Christopher W. Plummer
Abstract: The invention relates to stable formulations of antibodies against human programmed death receptor PD-1, or antigen binding fragments thereof. In some embodiments the formulations of the invention comprise between 5-200 mg/mL anti-PD-1 antibody, or antigen binding fragment thereof. The invention further provides methods for treating various cancers with stable formulations of the invention. In some embodiments of the methods of the invention, the formulations are administered to a subject by intravenous or subcutaneous administration.
Type:
Application
Filed:
May 1, 2018
Publication date:
May 14, 2020
Applicant:
Merck Sharp & Dohme Corp.
Inventors:
Manoj K. Sharma, Wendy Benjamin, Sarita Mittal, Ashwin Basarkar, Chakravarthy Nachu Narasimhan, Ramesh S. Kashi, Mohammed Shameem, Soumendu Bhattacharya, William P. Forrest, JR., Yogita Krishnamachari
Abstract: The present invention relates to novel Heterocycle-Substituted Tetracyclic Compounds of Formula (I): (I) and pharmaceutically acceptable salts thereof, wherein A, A?, R2 R3 and R5 are as defined herein. The present invention also relates to compositions comprising at least one Heterocycle-Substituted Tetracyclic Compound, and methods of using the Heterocycle-Substituted Tetracyclic Compounds for treating or preventing HCV infection in a patient.
Type:
Grant
Filed:
August 14, 2017
Date of Patent:
May 12, 2020
Assignee:
Merck Sharp & Dohme Corp.
Inventors:
Wensheng Yu, Ling Tong, Joseph A. Kozlowski, Craig A. Coburn, De-Yi Yang, Deyou Sha, Jae-Hun Kim, Michael Dwyer, Kartik M Keertikar, Bin Hu, Bin Zhong, Jinglai Hao, Dahai Wang
Abstract: The present invention is directed to pyrimidine carboxamide compounds of formula I which are useful as therapeutic agents for the treatment of central nervous system disorders associated with phosphodiesterase 2 (PDE2). The present invention also relates to the use of such compounds for treating neurological and psychiatric disorders, such as schizophrenia, psychosis, Parkinson's disease, Parkinson's disease dementia (PDD), or Huntington's disease, and those associated with striatal hypofunction or basal ganglia dysfunction.
Type:
Grant
Filed:
June 20, 2016
Date of Patent:
May 12, 2020
Assignee:
Merck Sharp & Dohme Corp.
Inventors:
Gregori J. Morriello, Lehua Chang, Ashley Forster, Richard Berger, Kausik K. Nanda, William D. Shipe
Abstract: Disclosed herein is a compound of formula (I), or a pharmaceutically acceptable salt thereof: Also disclosed herein are uses of a compound disclosed herein in the potential treatment or prevention of an IDO-associated disease or disorder. Also disclosed herein are compositions comprising a compound disclosed herein. Further disclosed herein are uses of a composition in the potential treatment or prevention of an IDO-associated disease or disorder.
Type:
Grant
Filed:
November 12, 2018
Date of Patent:
May 12, 2020
Assignee:
Merck Sharp & Dohme Corp.
Inventors:
Yongxin Han, Abdelghani Achab, Yongqi Deng, Xavier Fradera, Craig Gibeau, Brett A. Hopkins, Derun Li, Kun Liu, Meredeth A. McGowan, Nunzio Sciammetta, David Sloman, Catherine White, Hongjun Zhang, Hua Zhou
Abstract: The present disclosure provides antibodies and antigen binding fragments thereof including, but not limited to, monoclonal antibodies that specifically bind to human programmed death ligand 2 (PD-L2). The invention further provides nucleic acids encoding the antibodies and antigen binding fragments of the invention and host cells transformed therewith. The antibodies and antigen binding proteins of the invention are useful in methods for the immunohistochemical detection of human PD-L2 expression in tissue samples.
Type:
Grant
Filed:
September 20, 2016
Date of Patent:
May 12, 2020
Assignee:
Merck Sharp & Dohme Corp.
Inventors:
Jennifer H. Yearley, Linda Liang, Michael Eric Bigler, Christopher John Gibson
Abstract: Novel compounds of the structural formula (I), and the pharmaceutically acceptable salts thereof, are inhibitors of Nav1.8 channel activity and may be useful in the treatment, prevention, management, amelioration, control and suppression of diseases mediated by Nav1.8 channel activity. The compounds of the present invention may be useful in the treatment, prevention or management of pain disorders, cough disorders, acute itch disorders, and chronic itch disorders.
Type:
Application
Filed:
October 31, 2019
Publication date:
May 7, 2020
Applicant:
Merck Sharp & Dohme Corp.
Inventors:
Ashok Arasappan, Ian M. Bell, Michael J. Breslin, Christopher James Bungard, Christopher S. Burgey, Harry R. Chobanian, Jason M. Cox, Anthony T. Ginnetti, Deodial Guy Guiadeen, Kristen L. G. Jones, Mark E. Layton, Hong Liu, Jian Liu, James J. Perkins, Shawn J. Stachel, Linda M. Suen-Lai, Zhe Wu
Abstract: The present invention is directed to pyrazolopyrimidine compounds of the general structural formula I: which may be useful as therapeutic agents for the treatment of disorders associated with phosphodiesterase 9 (PDE9). The present invention also relates to the use of such compounds for treating cardiovascular and cerebrovascular diseases, such as hypertension, chronic kidney disease and heart failure, and neurological and psychiatric disorders, such as schizophrenia, psychosis or Huntington's disease, and those associated with striatal hypofunction or basal ganglia dysfunction.
Type:
Application
Filed:
October 31, 2019
Publication date:
May 7, 2020
Applicant:
Merck Sharp & Dohme Corp.
Inventors:
Ashok ARASAPPAN, Jason M. COX, John S. DEBENHAM, Zhuyan GUO, Jiafang HE, Zahid HUSSAIN, Zhong LAI, Derun LI, Dongfang MENG, Subharekha RAGHAVAN, Sriram TYAGARAJAN
Abstract: The present invention relates to anti-CD27 antibodies, as well as use of these antibodies in the treatment of diseases such as cancer and infectious disease.
Inventors:
Amy M. Beebe, Jason Ka Jen Cheung, Veronica Juan, Laurence Fayadat-Dilman, Svetlana Sadekova, Jerelyn Wong, Hans van Eenennaam, Andrea van Elsas, Lars Guelen, Thierry Olivier Fischmann, Winifred W. Prosise
Abstract: Disclosed are compounds of Formula A, or a salt thereof: Formula (A), wherein: Het, Q and R1A to R4A are defined herein, which compounds have properties for blocking Nav 1.7 ion channels found in peripheral and sympathetic neurons. Also described are pharmaceutical formulations comprising the compounds of Formula A or their salts, and methods of treating cough, itch, acute pain and neuropathic pain disorders using the same.
Type:
Application
Filed:
November 13, 2017
Publication date:
April 30, 2020
Applicant:
Merck Sharp & Dohme Corp.
Inventors:
Thomas J. Greshock, James Mulhearn, Anthony J. Roecker, Tianying Jian, Gang Zhou, Liangqin Guo, Walter Won, Ting Zhang, Rajan Anand, John E. Stelmach, Deping Wang, Ronald M. Kim, Mark E. Layton, Christopher S. Burgey, Philippe G. Nantermet
Abstract: The present invention relates to purified antibody and antigen-binding fragment compositions that lack sulfated tyrosine on one or more tyrosine residues in the immunoglobulin chains. Purification methods for removing sulfated tyrosine variants from antibody and antigen-binding fragment compositions are also provided.
Abstract: The present invention relates to Spirocyclic Pyridotriazine Derivatives of Formula (I) and pharmaceutically acceptable salts thereof, wherein A, B, X, Y, R1, R2 and R10 are as defined herein. The present invention also relates to compositions comprising at least one Spirocyclic Pyridotriazine Derivative, and methods of using the Spirocyclic Pyridotriazine Derivatives for treating or preventing HIV infection in a subject.
Type:
Grant
Filed:
November 11, 2016
Date of Patent:
April 21, 2020
Assignee:
Merck Sharp & Dohme Corp.
Inventors:
Thomas H. Graham, Tao Yu, Sherman T. Waddell, John A. McCauley, Andrew Stamford, Wengsheng Liu, Jay A. Grobler, Libo Xu
Abstract: A proof of provenance system receives database logs from an existing system that does not natively provide data provenance verification. The system produces a local representation of the database (or a portion thereof). The system periodically or in response to another triggering event flattens the local representation of the database to generate an aggregated slice, which is stored in an aggregated slice store. A reduced representation of the aggregated slice (e.g., a hash or checksum) is determined and appended to a distributed ledger, such as a blockchain. The provenance of data from the existing system can then be verified by redetermining the reduced representation and comparing it to the version appended to the distributed ledger.
Abstract: The present invention relates to method for treating cancer comprising administering an antagonist of PD-1, e.g., anti-PD-1 antibody or antigen binding fragment thereof, and an anti-CTLA4 antibody or antigen binding fragment thereof, wherein the CTLA4 antibody or antigen binding fragment thereof is given at a fixed dose. Also provided are compositions and kits comprising a dosage of an anti-PD-1 antibody and a dosage of an anti-CTLA4 antibody, and uses thereof.
Type:
Application
Filed:
March 28, 2018
Publication date:
April 16, 2020
Applicant:
Merck Sharp & Dohme Corp.
Inventors:
Blanca Homet Moreno, Nageatte Ibrahim, Scot W. Ebbinghaus, Lokesh Jain, Scott Diede
Abstract: Therapies comprising administering at least one cyclic dinucleotide compound that activates the Stimulator of Interferon Genes (STING) pathway, and the use of such therapies in the treatment of cell-proliferation disorders such as cancer, are disclosed herein.
Type:
Application
Filed:
December 15, 2017
Publication date:
April 16, 2020
Applicant:
Merck Sharp & Dohme Corp.
Inventors:
Saso Cemerski, Jared N. Cumming, Lauren M. Flateland, Johnny E. Kopinja, Yanhong Ma, Samanthi A. Perera, Benjamin Wesley Trotter, Archie Ngai-Chiu Tse
Abstract: The present invention relates to anti-TIGIT antibodies, as well as use of these antibodies in the treatment of diseases such as cancer and infectious disease.
Type:
Grant
Filed:
November 20, 2017
Date of Patent:
April 14, 2020
Assignee:
Merck Sharp & Dohme Corp.
Inventors:
Sybil M. G. Williams, Drake LaFace, Laurence Fayadat-Dilman, Gopalan Raghunathan, Linda Liang, Wolfgang Seghezzi
Abstract: This invention provides an improved processes for the preparation of verubecestat (Compound of Formula (I)), a potent inhibitor of BACE-1 and BACE-2.
Type:
Grant
Filed:
February 10, 2017
Date of Patent:
April 14, 2020
Assignee:
Merck Sharp & Dohme Corp.
Inventors:
William J. Morris, David Thaisrivongs, Thomas W. Lyons