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
Abstract: 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:
Application
Filed:
March 5, 2021
Publication date:
June 24, 2021
Applicant:
Merck Sharp & Dohme Corp.
Inventors:
Stephanie Elizabeth Barrett, Marian E. Gindy, Li Li, Seth P. Forster, Ryan S. Teller
Abstract: The present invention is directed carbocyclic nucleoside reverse transcriptase inhibitors compounds of Formula I and their use in the inhibition of HIV reverse transcriptase, 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 and/or ARC.
Abstract: An insulin conjugate comprising or consisting of a tri-valent sugar cluster is described. In particular aspects, the insulin conjugate displays 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 such as Con A.
Type:
Grant
Filed:
March 19, 2018
Date of Patent:
June 22, 2021
Assignee:
Merck Sharp & Dohme Corp.
Inventors:
Danqing Feng, Pei Huo, Ahmet Kekec, Songnian Lin, Christopher R. Moyes, Ravi Nargund, Brenda Pipik, Dmitri A. Pissarnitski, Lin Yan, Yuping Zhu
Abstract: Disclosed herein is a compound of formula (I), or a pharmaceutically acceptable salt thereof (I). Also disclosed herein are uses of the compounds 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 the compositions in the potential treatment or prevention of an IDO-associated disease or disorder.
Type:
Application
Filed:
October 29, 2018
Publication date:
June 17, 2021
Applicant:
Merck Sharp & Dohme Corp.
Inventors:
Yongqi Deng, Abdelghani Achab, Bridget A. Becker, David Jonathan Bennett, Indu Bharathan, Xavier Fradera, Craig Gibeau, Yongxin Han, Derun Li, Kun Liu, Qinglin Pu, Sulagna Sanyal, David Sloman, Wensheng Yu, Hongjun Zhang
Abstract: The present disclosure provides conjugates which comprise an insulin molecule conjugated via a conjugate framework to one or more separate ligands that include a first saccharide, and wherein the conjugate framework also comprises a fatty chain (e.g., a C8-30 fatty chain). In certain embodiments, a conjugate is characterized in that, when the conjugate is administered to a mammal, at least one pharmacokinetic (PK) and/or pharmacodynamic (PD) property of the conjugate is sensitive to serum concentration of a second saccharide. In certain embodiments, a conjugate is also characterized by having a protracted PK profile. Exemplary conjugates and sustained release formulations are provided in addition to methods of use and preparation.
Type:
Application
Filed:
December 13, 2018
Publication date:
June 17, 2021
Applicants:
Merck Sharp & Dohme Corp., SmartCells, Inc.
Inventors:
Lin Yan, Pei Huo, Ahmet Kekec, Yuping Zhu, Dmitri Pissarnitski, Danqing D. Feng, Chris Moyes, Zhiqiang Zhao, David N. Hunter, Songnian Lin, Thomas M. Lancaster, Benjamin Chen
Abstract: 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 diseases caused by S. pneumoniae.
Type:
Application
Filed:
December 4, 2018
Publication date:
June 17, 2021
Applicant:
Merck Sharp & Dohme Corp.
Inventors:
William J. Smith, Patrick McHugh, Michael Albert Winters, Julie M. Skinner, Jian He, Luwy Musey, Chitrananda Abeygunawardana, Yadong Adam Cui, Michael J. Kosinski
Abstract: Disclosed herein is a compound of formula (I), or a pharmaceutically acceptable salt thereof. Also disclosed herein are uses of the compounds 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 the compositions in the potential treatment or prevention of an IDO-associated disease or disorder.
Type:
Grant
Filed:
March 23, 2018
Date of Patent:
June 15, 2021
Assignee:
Merck Sharp & Dohme Corp.
Inventors:
Liangqin Guo, Yongxin Han, Kun Liu, Shuwen He, Joseph Kozlowski, Ravi Nargund, Wensheng Yu, Hongjun Zhang, Qinglin Pu, Derun Li, Abdelghani Achab, Guoqing Li
Abstract: A composition comprising (S)—N-(3-(6-isopropoxypyridin-3-yl)-1H-indazol-5-yl)-1-(2-(4-(4-(1-methyl-1H-1,2,4-triazol-3-yl)phenyl)-3,6-dihydropyridin-1(2H)-yl)-2-oxoethyl)-3-(methylthio)pyrrolidine-3-carboxamide and hypromellose acetate succinate for pharmaceutical preparations, especially capsule preparations.
Abstract: Approaches for the automatic segmentation of magnetic resonance (MR) images. Machine learning models segment images to identify image features in consecutive frames at different levels of resolution. A neural network block is applied to groups of MR images to produce primary feature maps at two or more levels of resolution. The images in a given group of MR images may correspond to a cycle and have a temporal order. A second RNN block is applied to the primary feature maps to produce two or more output tensors at corresponding levels of resolution. A segmentation block is applied to the two or more output tensors to produce a probability map for the MR images. The first neural network block may be a convolutional neural network (CNN) block. The second neural network block may be a convolutional long short-term (LSTM) block.
Type:
Grant
Filed:
May 30, 2019
Date of Patent:
June 8, 2021
Assignees:
Merck Sharp & Dohme Corp., MSD International GmbH
Abstract: The present disclosure relates to compounds of formula (I) that are useful as modulators of ?7 nAChR, compositions comprising such compounds, and the use of such compounds for preventing, treating, or ameliorating disease, particularly disorders of the central nervous system such as cognitive impairments in Alzheimer's disease, Parkinson's disease, and schizophrenia, as well as for L-DOPA induced-dyskinesia and inflammation.
Type:
Grant
Filed:
October 30, 2017
Date of Patent:
June 8, 2021
Assignee:
Merck Sharp & Dohme Corp.
Inventors:
Brendan M. Crowley, Ian M. Bell, Andrew John Harvey, Brian T. Campbell, Thomas J. Greshock, Vanessa L. Rada
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:
Grant
Filed:
October 31, 2019
Date of Patent:
June 8, 2021
Assignee:
Merck Sharp & Dohme Corp.
Inventors:
Ashok Arasappan, Jason M. Cox, John S. Debenham, Zahid Hussain, Derun Li, Dongfang Meng, Subharekha Raghavan
Abstract: Described herein are compounds of Formula (I) or a pharmaceutically acceptable salt thereof. The compounds of Formula (I) act as arginase inhibitors and can be useful in preventing, treating or acting as a remedial agent for arginase-related diseases.
Type:
Application
Filed:
June 14, 2019
Publication date:
June 3, 2021
Applicant:
Merck Sharp & Dohme Corp.
Inventors:
Abdelghani Abe Achab, Jared N. Cumming, Christian Fischer, Symon Gathiaka, Charles A. Lesburg, Derun Li, Min Lu, Matthew J. Mitcheltree, Anandan Palani, Rachel L. Palte, David L. Sloman, Hongjun Zhang
Abstract: Disclosed herein are compounds of formula (I) which are inhibitors of an IDO enzyme (I). Also disclosed herein are uses of the compounds in the potential treatment or prevention of an IDO-associated disease or disorder. Also disclosed herein are compositions comprising these compounds. Further disclosed herein are uses of the compositions in the potential treatment or prevention of an IDO-associated disease or disorder.
Type:
Application
Filed:
August 12, 2019
Publication date:
June 3, 2021
Applicant:
Merck Sharp & Dohme Corp.
Inventors:
Dane Clausen, Xavier Fradera, Yongxin Han, Alexander Pasternak, Li Xiao, Hongjun Zhang
Abstract: The present invention relates to insulin analogues and processes of making such insulin analogues by direct conversion of a free amine to an azide via diazo-transfer with an azotransfer agent.
Type:
Application
Filed:
April 8, 2019
Publication date:
June 3, 2021
Applicant:
Merck Sharp & Dohme Corp.
Inventors:
Sobhana Babu Boga, Ahmet Kekec, Songnian Lin, Craig A. Parish, Weijuan Tang, Lin Yan
Abstract: The present invention is directed to 4?-substituted nucleoside derivatives of Formula I and their use in the inhibition of HIV reverse transcriptase, 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 and/or ARC. The present invention also provides processes for the preparation of 4?-substituted nucleoside derivatives of Formula I and derivatives thereof.
Inventors:
Mark McLaughlin, Edward Cleator, Jongrock Kong, Andrew William Gibson, David R. Lieberman, Alejandro Diequez Vazquez, Stephen Philip Keen, Michael J. Williams, Jeffrey C. Moore, Erika M. Milczek, Feng Peng, Kevin M. Belyk, Zhiguo Jake Song
Abstract: The present invention relates to methods for producing a stable amorphous dispersion of a pharmaceutically active substance having poor water solubility by applying low frequency acoustic energy to a mixture comprising the active substance and at least one polymer and heating the mixture until a stable amorphous dispersion is formed. The methods of the invention are an effective means of converting a crystalline API to a substantially amorphous and stable form, i.e., wherein the crystallinity is less than about 5%. The methods of the invention result in more complete amorphization, increased solubility, drug loading and stability as compared typical amorphization or literature methods.
Type:
Application
Filed:
August 20, 2018
Publication date:
May 27, 2021
Applicant:
Merck Sharp & Dohme Corp.
Inventors:
Dennis H. Leung, Zhiqiang Guo, Christopher W. Boyce
Abstract: Crystals of pembrolizumab and structurally similar anti-PD-1 monoclonal antibodies are provided, as well as methods of producing such crystals, and uses of compositions comprising such antibody crystals, e.g. in treatment of cancers. The present invention satisfies these needs and more by providing pembrolizumab crystals and a method producing pembrolizumab crystals. One embodiment of the method of the invention produces crystals suitable for X-ray diffraction, and the inventors herein used such crystals to solve the three-dimensional structure of pembrolizumab to 2.3 A resolution.
Type:
Grant
Filed:
February 22, 2016
Date of Patent:
May 25, 2021
Assignee:
Merck Sharp & Dohme Corp.
Inventors:
Paul Reichert, Winifred W. Prosise, Giovanna Scapin, Xiaoyu Yang, Ramesh Kashi, Corey Strickland
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 XIIa inhibitors.
Type:
Grant
Filed:
November 13, 2017
Date of Patent:
May 25, 2021
Assignee:
Merck Sharp & Dohme Corp.
Inventors:
Jacqueline D. Hicks, Brian Alexander McKittrick, Brent R. Whitehead, Matthew Lombardo, Xiaoqing Han, Jerry A. Taylor, Hong Dong Chu, Sung-Sau So, Peter Orth, Zhicai Wu
Abstract: A protein crystallization trial is automatically analyzed by capturing images of the protein drops in the trial. A machine-learned model, such as a neural network, is applied to classify the images. The model generates a predicted classification from among a set of possible classifications which includes one or more crystal type classifications and one or more non-crystal type classifications. Users may be notified automatically of newly identified crystals (e.g., drops that are classified as a crystal type). The notification may include a link to a user interface that includes results of the trial.
Type:
Grant
Filed:
February 1, 2019
Date of Patent:
May 18, 2021
Assignee:
Merck Sharp & Dohme Corp.
Inventors:
Soheil Ghafurian, Ilknur Icke, Charles A. Lesburg, Belma Dogdas