Abstract: The present invention relates to biaryl monobactam compounds of Formula I: and pharmaceutically acceptable salts thereof, wherein X, Y, Z, A1, Q, M, W, RX and Rz are as defined herein. The present invention also relates to compositions which comprise a biaryl monobactam compound of the invention or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier. The invention further relates to methods for treating a bacterial infection comprising administering to the patient a therapeutically effective amount of a compound of the invention, either alone or in combination with a therapeutically effective amount of a second beta-lactam antibiotic.
Type:
Application
Filed:
December 12, 2016
Publication date:
November 29, 2018
Applicant:
Merck Sharp & Dohme Corp.
Inventors:
Haifeng Tang, Weiguo Liu, Fa-Xiang Ding, Wanying Sun, Yi Zang, Weidong Pan, Anthony Ogawa, Linda Brockunier, Xianhai Huang, Hongwu Wang, Rudrajit Mal, Tesfaye Biftu, Min Park, Yan Guo, Jinlong Jiang, Helen Y. Chen, Christopher W. Plummer
Abstract: The present invention provides a compound of Formula (I) and pharmaceutical compositions comprising one or more said compounds, and methods for using said compounds for treating or preventing thromboses, embolisms, hypercoagulability or fibrotic changes. The compounds are selective Factor XIa inhibitors or dual inhibitors of Factor XIa and plasma Kallikrein.
Type:
Application
Filed:
October 24, 2016
Publication date:
November 29, 2018
Applicant:
MERCK SHARP & DOHME CORP.
Inventors:
Jiayi Xu, Amjad Ali, Wei Zhou, Ying-Duo Gao, Scott D. Edmondson, Eric Mertz, Santhosh F. Neelamkavil, Weiguo Liu, Wanying Sun, Dong-Ming Shen, Bart Harper, Cheng Zhu, Thomas Bara, Yeon-Hee Lim, Meng Yang
Abstract: The present invention provides dengue virus vaccines and immunogenic compositions for administration to human subjects. The vaccine compositions of the present invention comprise recombinantly produced monomeric and/or dimeric forms of truncated dengue virus envelope glycoprotein that, when formulated together with an adjuvant and a pharmaceutically acceptable carrier, induce balanced tetravalent immune responses. In preferred embodiments of the compositions described herein, the DEN4 protein component is a dimeric form of DEN4. The compositions are designed to be acceptable for use in the general population, including immunosuppressed, immunocompromised, and immunosenescent individuals. Also provided herein are methods of inducing a protective immune response in a human patient population by administering the compositions described herein to the patients.
Type:
Grant
Filed:
September 22, 2015
Date of Patent:
November 27, 2018
Assignee:
Merck Sharp & Dohme Corp.
Inventors:
Beth-Ann Griswold Coller, Vidya B. Pai, Jr., D. Elliot Parks, Michele Yelmene, Andrew J. Bett, Timothy Martyak
Abstract: The present invention is directed to compounds of Formula I pharmaceutical compositions comprising the same, and their use in the inhibition of HIV protease, the inhibition of HIV replication, the prophylaxis of infection by HIV, the treatment of infection by HIV, and the prophylaxis, treatment, and delay in the onset or progression of AIDS.
Inventors:
Peter D. Williams, John A. McCauley, Christopher J. Bungard, David Jonathan Bennett, Sherman T. Waddell, Gregori J. Morriello, Lehua Chang, Michael P. Dwyer, M. Katharine Holloway, Alejandro Crespo, Xin-Jie Chu, Catherine Wiscount, H. Marie Loughran, Jesse J. Manikowski, Jurgen Schulz, Kartik M. Keertikar, Bin Hu, Bin Zhong, Tao Ji
Abstract: The present invention is directed to compounds of generic formula I: or pharmaceutically acceptable salts thereof that are believed to be useful as an A2A-receptor antagonist.
Type:
Grant
Filed:
February 1, 2016
Date of Patent:
November 27, 2018
Assignee:
Merck Sharp & Dohme Corp.
Inventors:
Amjad Ali, Rongze Kuang, Yeon-Hee Lim, Michael Man-Chu Lo, Pauline C. Ting, Purakkattle Biju, Manuel de Lera Ruiz, Sylvia J. Degrado, Alexander L. Tung, Timothy J. Henderson, Liwu Hong, Jae-Hun Kim, Dong Won-Shik Kim, Joe Lee, Jie Wu, Heping Wu, Yushi Xiao, Tao Yu, Gang Zhou, Xiaohong Zhu, Kevin D. McCormick, Jayaram R. Tagat, Dong Xiao, Tanweer Khan, Jianhua Cao, Michael Berlin, Yonglian Zhang
Abstract: Therapeutic combinations of immunoconjugates that bind to FOLR1 (e.g., IMGN853) with anti-PD-1 antibodies or antigen-binding fragments thereof (e.g., pembrolizumab) are provided. Methods of administering the combinations to treat cancers, e.g., ovarian, peritoneal, or fallopian tube cancers, with greater clinical efficacy and/or decreased toxicity are also provided.
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 5, 2015
Date of Patent:
November 20, 2018
Assignee:
Merck Sharp & Dohme Corp.
Inventors:
Harry Chobanian, Duane DeMong, Christopher W. Plummer, Minghai Fang, Bin Hu
Abstract: The present invention is directed to a process for preparing Substituted Indole Compounds of Formula (I): wherein R1, R2, R3 and R4 are as defined herein. These indole compounds are useful as synthetic intermediates for making inhibitors of HCV NS5A.
Type:
Grant
Filed:
November 5, 2015
Date of Patent:
November 20, 2018
Assignee:
Merck Sharp & Dohme Corp.
Inventors:
Daniel A. DiRocco, Ian Davies, Feng Peng, Mark McLaughlin, Louis-Charles Campeau, Yingju Xu
Abstract: Intelligent cold storage system for storing pharmaceutical product containers, such as vials, ampules, syringes, bottles, medication tubes, blister packs and cartons, at the point of dispensing. Embodiments of the invention use product identification technology, such as radio-frequency identification (RFID) tags and barcode readers, to uniquely identify containers as they are added to or removed from the cold storage compartment, and automatically retrieve from a local or remote database a variety of details associated with the containers and their contents, such as manufacturing data, expiration dates, time out of refrigeration, inventory levels, safety information, usage statistics, known contraindications and warnings, etc. If the details indicate that there is a problem with a particular pharmaceutical (e.g.
Abstract: The present invention provides Bruton's Tyrosine Kinase (Btk) inhibitor compounds according to Formula (I), or pharmaceutically acceptable salts or stereoisomers thereof, or to pharmaceutical compositions comprising these compounds and to their use in therapy. In particular, the present invention relates to the use of Btk inhibitor compounds of Formula (I) in the treatment of Btk mediated disorders.
Type:
Grant
Filed:
December 17, 2015
Date of Patent:
November 20, 2018
Assignee:
MERCK SHARP & DOHME CORP.
Inventors:
Jian Liu, Joseph A. Kozlowski, Abdul-Basit Alhassan, Rajan Anand, Sobhana Babu Boga, Deodial Guy Guiadeen, Wensheng Yu, Younong Yu, Shilan Liu, Hao Wu, Chundao Yang
Abstract: In its many embodiments, the present invention provides substituted cyanopyridine containing compounds of the Formula (I): and acceptable salts thereof, wherein R1, R2, R3, R4, R5, X, Y, Q, and the moiety are as defined herein. The novel compounds of the invention, and pharmaceutically acceptable compositions comprising a compound thereof, are useful as Liver X-? receptor (LXR?) agonists, and may be useful for treating or preventing pathologies related thereto. Such pathologies include, but are not limited to, inflammatory diseases and diseases characterized by defects in cholesterol and lipid metabolism, such as Alzheimer's disease.
Type:
Application
Filed:
November 7, 2016
Publication date:
November 15, 2018
Applicant:
Merck Sharp & Dohme Corp.
Inventors:
Michael T. Rudd, Edward J. Brnardic, Yuntae Kim, Robert S. Meissner, Vanessa L. Rada, Shawn J. Stachel, Celina V. Zerbinatti
Abstract: A gene expression platform, which is a combination of a set of genes that are correlated with response to a PD-1 antagonist in multiple tumor types and a normalization gene set, is disclosed. A method and system of using the gene expression platform to derive gene signature biomarkers of anti-tumor response to a PD-1 antagonist and to test patient samples for predictive gene signature biomarkers are also disclosed.
Type:
Application
Filed:
December 8, 2015
Publication date:
November 15, 2018
Applicant:
Merck Sharp & Dohme Corp.
Inventors:
Mark D. Ayers, Andrey Loboda, Jared K. Lunceford, Terrill K. McClanahan, Erin E. Murphy, Michael Nebozhyn
Abstract: Disclosed are compounds of Formula A and Formula A-1, or a salt thereof, and pharmaceutical formulations (pharmaceutical compositions) comprising those compounds, or a salt thereof; wherein “R1”, “RA-1”, “R2”, “R3”, and “Het” are defined herein above, which compounds are believed suitable for use in selectively antagonizing the A2a receptors, for example, those found in high density in the basal ganglia. Such compounds and pharmaceutical formulations are believed to be useful in treatment or management of neurodegenerative diseases, for example, Parkinson's disease, or movement disorders arising from use of certain medications used in the treatment or management of Parkinson's disease.
Type:
Application
Filed:
November 13, 2015
Publication date:
November 15, 2018
Applicant:
Merck Sharp & Dohme Corp.
Inventors:
Rongze KUANG, Pauline Ting, Amjad Ali, Heping Wu, Michael Berlin, Andrew Stamford, Hongwu Wang, Gang Zhou, David Kim, Qiaolin Deng, Yeon-Hee Lim, Younong Yu
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 R16 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:
Application
Filed:
November 11, 2016
Publication date:
November 15, 2018
Applicant:
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: The present invention relates to Amido-Substituted Pyridotriazine Derivatives of Formula (I): (I) and pharmaceutically acceptable salts thereof, wherein B, X, Y, R, R1, R2 and R10 are as defined herein. The present invention also relates to compositions comprising at least one Amido-Substituted Pyridotriazine Derivative, and methods of using the Amido-Substituted Pyridotriazine Derivatives for treating or preventing HIV infection in a subject.
Type:
Application
Filed:
November 11, 2016
Publication date:
November 15, 2018
Applicant:
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: An injector for delivering liquid can include a body having a proximal end, a distal end, a longitudinal axis, and a track follower adjacent to the proximal end. A plunger can be disposed at least partially within the body and movable with respect to the body along the longitudinal axis. An actuator can be positioned at the proximal end of the body and operably connected to the plunger. The actuator can include a track having a first portion and a second portion. The first portion can limit travel of the actuator along the longitudinal axis to deliver a first predetermined amount of the liquid. The second portion can limit travel of the actuator along the longitudinal axis to deliver a second predetermined amount of the liquid. The actuator can be positionable to selectively control displacement of the plunger pursuant to the first portion or the second portion of the track.
Abstract: Provided herein is a method for the synthesis of cephalosporin antibiotic compounds comprising a palladium-catalyzed coupling reaction. Provided herein are methods for the synthesis of cephalosporin compounds of formula (I) employing a palladium-catalyzed alkylation reaction, as well as compositions related to the same. In an aspect, provided herein is a method for preparing a compound of formula (II), or a salt thereof, comprising the step of admixing, e.g., reacting, a compound of formula (III), or a salt thereof, with a nucleophile (Nuc) in the presence of reagents comprising: (a) a palladium source; and (b) a palladium-binding ligand, to form a compound of formula (II), or a salt thereof.
Type:
Grant
Filed:
August 14, 2015
Date of Patent:
November 13, 2018
Assignee:
Merck Sharp & Dohme Corp.
Inventors:
David Waller, Gregory Gazda, Zachary Minden, Lisa Barton, Clifton Leigh
Abstract: The present invention provides a compound of Formula (I) and pharmaceutical compositions comprising one or more said compounds, and methods for using said compounds for treating or preventing thromboses, embolisms, hypercoagulability or fibrotic changes. The compounds are selective Factor XIa inhibitors or dual inhibitors of Factor XIa and plasma kallikrein.
Type:
Grant
Filed:
January 15, 2016
Date of Patent:
November 13, 2018
Assignee:
Merck Sharp & Dohme Corp.
Inventors:
Eric Mertz, Weiguo Liu, Scott D. Edmondson, Amjad Ali, Ying-Duo Gao, Santhosh F. Neelamkavil, Sung-Sau So, Remond Moningka, Wanying Sun, Alan Hruza, Linda L. Brockunier
Abstract: A method for crystallizing insulin or insulin analogs under alkaline conditions in the presence of zinc, purifying the crystals by filtering through a filter, and drying the crystals captured on the filter to produce crystalline insulin or insulin analog compositions is described. Method has been exemplified with insulin lispro.
Type:
Grant
Filed:
August 21, 2015
Date of Patent:
November 13, 2018
Assignee:
Merck Sharp & Dohme Corp.
Inventors:
Douglas S. Watson, Allison C. Ortigosa, Mark C. Sleevi, Kathryn M. Story
Abstract: Disclosed is a pharmaceutical formulation comprising an insulin or insulin analog molecule covalently attached to at least one branched linker having a first arm and second arm, wherein the first arm is linked to a first ligand that includes a first saccharide and the second arm is linked to a second ligand that includes a second saccharide and wherein the first saccharide is fucose. The formulation is suitable for subcutaneous administration and provides a basal pharmacodynamic profile for the insulin oligosaccharide conjugate.
Type:
Application
Filed:
April 30, 2018
Publication date:
November 8, 2018
Applicant:
MERCK SHARP & DOHME CORP.
Inventors:
Shuai Shi, Valentyn Antochshuk, Joseph Rizzo, Niels C. Kaarsholm