Patents Assigned to Merck Sharp and Dohme Corp.
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Publication number: 20220380854Abstract: The invention relates to (i) an angiogenesis gene signature and (ii) a monocytic myeloid-derived suppressor cell (mMDSC) gene signature that are each predictive of patient response to treatment with a PD-1 antagonist, wherein the angiogenesis signature comprises five or more genes. More specifically, a lower angiogenesis score is associated with favorable response to a PD-1 antagonist in a patient with cancer. Similarly, a lower mMDSC score is associated with favorable response to a PD-1 antagonist in a patient with cancer. Also provided are methods of treating a cancer patient with a PD-1 antagonist that were identified as either (i) positive for the angiogenesis gene signature biomarker of the invention or (ii) positive for the mMDSC gene signature biomarker of the invention.Type: ApplicationFiled: October 29, 2020Publication date: December 1, 2022Applicant: Merck Sharp & Dohme Corp.Inventors: Mark D. Ayers, Razvan Cristescu, Andrey Loboda, Jared K. Lunceford, Hua Ma, Terrill K. McClanahan, Michael Nebozhyn, Chunsheng Zhang
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Publication number: 20220380469Abstract: The present invention relates to methods for treating metastatic triple negative breast cancer in a human patient which has been identified as having a PD-L1 enriched tumor comprising administering, as monotherapy, an anti-PD-1 antibody or antigen binding fragment thereof (e.g., pembrolizumab) in specific amounts to the patient about every three or six weeks, wherein the PD-L1 enriched tumor is a tumor identified as having a CPS score of ?10.Type: ApplicationFiled: September 23, 2020Publication date: December 1, 2022Applicant: Merck Sharp & Dohme Corp.Inventors: Gursel Aktan, Roger Delemere Dansey, Vassiliki Karantza, Zifang Guo, Jaime A. Mejia, Shu-Chih Su, Jing Zhao, Xuan Zhou
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Publication number: 20220363656Abstract: Novel compounds of the structural formula (I), and the pharmaceutically acceptable salts thereof, are antagonists of leukotriene B4 receptor 1 (BLT1) and may be useful in the treatment, prevention and suppression of diseases mediated by the leukotriene B4 receptor 1 (BLT1). The compounds of the present invention may be useful in the treatment of Type 2 diabetes mellitus, insulin resistance, hyperglycemia, dyslipidemia, lipid disorders, obesity, hypertension, Nonalcoholic fatty liver disease/nonalcoholic steatohepatitis, metabolic syndrome, atherosclerosis, and cancer.Type: ApplicationFiled: June 10, 2021Publication date: November 17, 2022Applicant: Merck Sharp & Dohme Corp.Inventors: Yongxin Han, Jongwon Lim, Satyanarayana Tummanapalli, Phieng Siliphaivanh, Kerrie Spencer
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Publication number: 20220363707Abstract: The present invention provides a compound of Formula (I) and the pharmaceutically acceptable salts, esters, and prodrugs thereof, which are PRMT5 inhibitors. Also provided are methods of making compounds of Formula I, pharmaceutical compositions comprising compounds of Formula I, and methods of using these compounds to treat cancer, sickle cell, and hereditary persistence of foetal hemoglobin (HPFH) mutations.Type: ApplicationFiled: August 5, 2019Publication date: November 17, 2022Applicants: Merck Sharp & Dohme Corp., MSD International GmbHInventors: Michelle Machacek, David Witter, Craig Gibeau, Chunhui Huang, Shuhei Kawamura, David L. Sloman, Phieng Siliphaivanh, Ryan Quiroz, Murray Wan, Sebastian Schneider, Charles S. Yeung, Michael H. Reutershan, Timothy J. Henderson, Jean-Laurent Paparin, Houcine Rahali, Jonathan M. E. Hughes, Sulagna Sanyal, Yingchun Ye, David A. Candito, Patrick S. Fier, Steven M. Silverman
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Publication number: 20220362277Abstract: This invention relates to novel implant drug delivery systems for long-acting delivery of antiviral drugs. These compositions are useful for the treatment or prevention of human immunodeficiency virus (HIV) infection.Type: ApplicationFiled: August 11, 2020Publication date: November 17, 2022Applicant: Merck Sharp & Dohme Corp.Inventors: Seth P. Forster, Stephanie Elizabeth Barrett, Ryan S. Teller, Morgan B. Giles, Athanas Koynov
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Publication number: 20220356182Abstract: The present invention relates to compounds of formula (I) that are useful as hepatitis C virus (HCV) NS5A inhibitors, the synthesis of such compounds, and the use of such compounds for inhibiting HCV NS5A activity, for treating or preventing HCV infections and for inhibiting HCV viral replication and/or viral production in a cell-based system.Type: ApplicationFiled: May 19, 2021Publication date: November 10, 2022Applicant: Merck Sharp & Dohme Corp.Inventors: Craig A. Coburn, Steven W. Ludmerer, Kun Liu, Hao Wu, Richard Soll, Bin Zhong, Jian Zhu
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Publication number: 20220340660Abstract: Novel methods for selecting a patient with a cancer for treatment with a TIGIT antagonist are disclosed. The methods employ various biomarkers, including CD45, CD3?, CD11b, Foxp3, IFN-?, Cxcl11, Cxcl10, TNF-?, IL-23, MHC class II, CD80, CD86, and CD40.Type: ApplicationFiled: October 1, 2019Publication date: October 27, 2022Applicant: Merck Sharp & Dohme Corp.Inventors: Sybil M.G. Williams, Jin-Hwan Han, Drake Maurice LaFace, Elaine Pinheiro, Wolfgang Seghezzi
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Patent number: 11479542Abstract: The disclosed subject matter provides certain polymorphic forms of Compound (I) as well as pharmaceutical compositions comprising Compound (I) or such polymorphic forms, and methods of using or making such compounds and pharmaceutical compositions. It has now been discovered that Compound (I) can exist in multiple crystalline forms (polymorphs). One particular crystalline form, Form II, has been found to be more thermodynamically stable and, thus, likely more suitable for bulk preparation and handling than other polymorphic forms. Efficient and economic methods have been developed to prepare Compound (I) and Form II in high purity on a large scale. In animal studies, Form II has demonstrated safety and efficacy in treating depressive disorders and, when micronized, improved absorption compared to non-micronized Form II.Type: GrantFiled: May 27, 2020Date of Patent: October 25, 2022Assignees: CERECOR, INC., MERCK SHARP & DOHME CORP.Inventors: Reza Mazhari, Djelila Mezaache, Blake M. Paterson, James Vornov, Rachel M. Garner, Todd Nelson
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Publication number: 20220331350Abstract: The present invention is directed to methods for inhibition of HIV reverse transcriptase, treatment of infection by HIV, prophylaxis of infection by HIV, and the treatment, prophylaxis and/or delay in the onset or progression of AIDS or ARC by administering a compound of structural Formula I or a pharmaceutically acceptable salt or co-crystal thereof, wherein X is —F or —Cl, less frequently than once daily.Type: ApplicationFiled: April 8, 2022Publication date: October 20, 2022Applicant: Merck Sharp & Dohme Corp.Inventors: Daria Hazuda, Michael D. Miller, Jay A. Grobler, Deborah Anne Nicoll-Griffith
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Publication number: 20220331321Abstract: Methods of treating malaria comprising administration of compounds of Formula (I?) or a pharmaceutically acceptable salt thereof, to a subject in need thereof, wherein the variables are as defined herein. It also provides uses of the compounds of Formula (I), as defined herein, for inhibiting plasmepsin X, plasmepsin IX or plasmepsin X and IX activity, for treating a Plasmodium infection, and for treating malaria. Also provided are methods of treatment further comprising administration of one or more additional anti-malarial compounds.Type: ApplicationFiled: July 21, 2020Publication date: October 20, 2022Applicants: Merck Sharp & Dohme Corp., The Walter and Eliza Hall Institute of Medical Research, MSD R & D (China) Co. LTD.Inventors: John A. McCauley, Alan F. Cowman, Manuel de Lera Ruiz, Paola Favuzza, Zhuyan Guo, Bin Hu, Michael J. Kelly, III, Zhiyu Lei, David B. Olsen, Brad Sleebs, Jennifer K. Thompson, Tony Triglia, Dongmei Zhan, Cailing Zhang, Lianyun Zhao
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Publication number: 20220334040Abstract: Embodiments of the present invention provide an apparatus and method for determining whether a dosage unit of a pharmaceutical dmg disintegrates in an immersion fluid of a disintegration tester within a prescribed time limit and to record and transmit to human-accessible output devices the times required. In one implementation, the apparatus comprises a computer system, a motion sensor, a capture device, a fastener for attaching the capture device and motion sensor to the reciprocating arm of the disintegration tester, and one or more data communications interfaces to carry commands and data between the computer system, the motion sensor and the capture device.Type: ApplicationFiled: September 29, 2020Publication date: October 20, 2022Applicant: Merck Sharp & Dohme Corp.Inventors: Grace Chen, Joanna C. Everitt, Sydney Floryanzia, Janakiraman Gopinath, Prashant I. Shah
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Publication number: 20220324979Abstract: The present disclosure describes combination therapies comprising an antagonist of Programmed Death 1 receptor (PD-1) and a VEGFR inhibitor, and the use of the combination therapies for the treatment of cancer, and in particular for treating cancers that express PD-L1.Type: ApplicationFiled: April 20, 2022Publication date: October 13, 2022Applicants: PFIZER INC., MERCK SHARP & DOHME CORP.Inventors: Jean-Francois Andre MARTINI, Jamal Christo Tarazi, Rodolfo Fleury Perini, David J. Mauro
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Publication number: 20220306619Abstract: The present invention is directed to pro drugs of 2-methyl-N-((5-methyl-1,3,4-thiadiazol-2-yl)methyl)-6-(((1S,2S)-2-(5-methylpyridin-2-yl)cyclopropyl)methoxy)pyrimidin-4-amine which are useful as therapeutic agents for the treatment of central nervous system disorders associated with phosphodiesterase 10 (PDE10). The present invention also relates to the use of such compounds for treating neurological and psychiatric disorders, such as schizophrenia, psychosis or Huntington's disease, and those associated with striatal hypofunction or basal ganglia dysfunction.Type: ApplicationFiled: March 15, 2022Publication date: September 29, 2022Applicant: Merck Sharp & Dohme Corp.Inventors: Sachin Mittal, Jason W. Skudlarek, Izzat T. Raheem
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Publication number: 20220305035Abstract: Disclosed are compounds of Formula A, or a salt thereof: Wherein “A1”, R1, R2, R3, R6, and R7 are as 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 and neuropathic pain disorders using the same.Type: ApplicationFiled: June 8, 2020Publication date: September 29, 2022Applicant: Merck Sharp & Dohme Corp.Inventors: Anthony J. Roecker, Mark E. Layton, Deping Wang, Xiu Wang, Xuanjia Peng
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Publication number: 20220296695Abstract: The invention is related to multivalent immunogenic compositions comprising more than one S. pneumoniae polysaccharide protein conjugates, wherein each of the conjugates comprises a polysaccharide from an S. pneumoniae serotype conjugated to a carrier protein, wherein the serotypes of S. pneumoniae are as defined herein. In some embodiments, at least one of the polysaccharide protein conjugates is formed by a conjugation reaction comprising an aprotic solvent. In further embodiments, each of the polysaccharide protein conjugates is formed by a conjugation reaction comprising an aprotic solvent. Also provided are methods for inducing a protective immune response in a human patient comprising administering the multivalent immunogenic compositions of the invention to the patient. The multivalent immunogenic compositions are useful for providing protection against S. pneumoniae infection and/or pneumococcal diseases caused by S. pneumoniae.Type: ApplicationFiled: December 17, 2019Publication date: September 22, 2022Applicant: Merck Sharp & Dohme Corp.Inventors: Chitrananda Abeygunawardana, Yadong Adam Cui, Romulo Ferrero, Jian He, Luwy Musey, Tanaz Petigara, Julie M. Skinner
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Publication number: 20220280636Abstract: The disclosure relates to HSV glycoprotein E antigenic peptide constructs and HSV protein vaccines, as well as methods of using the vaccines and compositions comprising the vaccines. The present invention directed to immunogenic polypeptides of use for a vaccine against Herpes Simplex Vims (HSV). The polypeptides are glycoprotein E peptides that are mutated to reduce their binding to antibody Fc domain.Type: ApplicationFiled: July 14, 2020Publication date: September 8, 2022Applicant: Merck Sharp & Dohme Corp.Inventors: Arthur Fridman, Jennifer Dawn Galli, Dai Wang, Lan Zhang
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Publication number: 20220281886Abstract: The present invention relates to Compounds of Formula I: I and pharmaceutically acceptable salts or prodrug thereof. The present invention also relates to compositions comprising at least one compound of Formula I, and methods of using the compounds of Formula I for treatment or prophylaxis of cardiometabolic diseases including high blood pressure, heart failure, kidney disease, and diabetes in a subject.Type: ApplicationFiled: May 18, 2020Publication date: September 8, 2022Applicant: Merck Sharp Dohme Corp.Inventors: Frank Bennett, Jason E. Imbriglio, Angela D. Kerekes, Tanweer Khan, Claire Lankin, Derun Li, Zhicai Wu, Yusheng Xiong, Hyewon Youm, Yang Yu, Feng Ye, Anthappan Tony Kurissery, Venukrishnan Komanduri
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Publication number: 20220273770Abstract: Glucose-responsive insulin conjugates that contain one or more trisaccharides are provided. Such insulin conjugates may display a pharmacokinetic (PK) and/or pharmacodynamic (PD) profile that is responsive to the systemic concentrations of a saccharide such as glucose or alpha-methylmannose, even when administered to a subject in need thereof in the absence of an exogenous multivalent saccharide-binding molecule.Type: ApplicationFiled: July 23, 2020Publication date: September 1, 2022Applicant: Merck Sharp & Dohme Corp.Inventors: Danqing Feng, Erin N. Guidry, Pei Huo, Andrew J. Kassick, Ahmet Kekec, Songnian Lin, Christopher R. Moyes, Dmitri A. Pissarnitski, Lin Yan, Yuping Zhu
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Publication number: 20220273669Abstract: The present invention relates to Compounds of Formula I: I and pharmaceutically acceptable salts or prodrug thereof. The present invention also relates to compositions comprising at least one compound of Formula I, and methods of using the compounds of Formula I for treatment of cardiometabolic diseases including high blood pressure, heart failure, kidney disease, and diabetes in a subject.Type: ApplicationFiled: May 18, 2020Publication date: September 1, 2022Applicant: Merck Sharp Dohme Corp.Inventors: Qingmei Hong, Jason E. Imbriglio, Angela D. Kerekes, Tanweer Khan, Claire Lankin, Derun Li, Rui Liang, Pengcheng Patrick Shao, Zhicai Wu, Yusheng Xiong, Feng Ye, Hyewon Youm, Yang Yu, Anthappan Tony Kurissery, Venukrishnan Komanduri
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Patent number: 11426730Abstract: A well plate assembly with an interior channel system in the well plate lid provides a more efficient and uniform distribution of fluid into a receptacle positioned below the well plate lid. The channel system in the lid allows air, or other fluid, to pass through with the use of a pump to each of a plurality of channels in the receptacle. Inlet and outlet valves in the lid prevent a gasket positioned between the lid and the receptacle from releasing contact with the receptacle due to high pressure experienced during the injection of fluid into the assembly. Specifically, pressure under a specified tolerance passes through the inlet valves, and if the pressure within the channel system exceeds the limit of the outlet valve, the outlet valve opens and allows air to escape the lid safely without disturbing the fluid flow into the channels below.Type: GrantFiled: February 24, 2020Date of Patent: August 30, 2022Assignee: Merck Sharp & Dohme Corp.Inventors: Tinh Nguyen-DeMary, William James Ciolino