Abstract: A reusable safety syringe training device is provided. The device comprises a syringe contained within a syringe protective member. The syringe protective member is movable vertically within an outer protective sheath from a first position to a second position and back to the first position. In the first position, the device is in an injection-ready position with the needle exposed and the syringe protective member in a locked vertical position with respect to the outer protective sheath. In the second position, the device is in a post-injection position such that the syringe protective member is no longer vertically locked with respect to the outer protective sheath and has moved vertically upward thereby rendering the needle within the outer protective sheath. The plunger carries a release flange sufficient to engage release latches that otherwise retain the syringe protective member in the first position.
Abstract: In its many embodiments, the present invention provides certain substituted N-aryl and N-heteroaryl piperidine compounds of the Formula (I): and pharmaceutically acceptable salts thereof, wherein R1, R2, R3, L, R4, L1, Q, R5 and R6 are as defined herein. The novel compounds of the invention, and pharmaceutically acceptable compositions comprising a compound thereof, may be 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:
October 9, 2017
Publication date:
February 6, 2020
Applicant:
Merck Sharp & Dohme Corp.
Inventors:
Michael T. Rudd, Zhaoyang Meng, Jenny Wai, David Jonathan Bennett, Edward J. Brnardic, Nigel J. Liverton, Shawn J. Stachel, Yongxin Han, Paul Tempest, Jiuxiang Zhu, Xuewang Xu
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:
Application
Filed:
February 10, 2017
Publication date:
February 6, 2020
Applicant:
Merck Sharp & Dohme Corp.
Inventors:
William J. Morris, David Thaisrivongs, Thomas W. Lyons
Abstract: The present invention provides an efficient process for culturing viruses in the presence of an endonuclease and for producing vaccines, typically from live attenuated viruses, under conditions to reduce the presence of host cell DNA and eliminate the need for a post-harvest DNA digestion step.
Type:
Application
Filed:
March 28, 2018
Publication date:
February 6, 2020
Applicant:
Merck Sharp & Dohme Corp.
Inventors:
Yi Li, Matthew Woodling, Adam Kristopeit
Abstract: A bubble is displayed in a visualization that is based on a number of distinct values pertaining to the concept and on a number of records in the dataset including at least one of the distinct values pertaining to the concept. Furthermore, the dataset includes records from one or more databases organized into a concept hierarchy. The bubble includes, for a level of the concept hierarchy, a plurality of indicators each representing one of the distinct values at the level of the concept hierarchy. An interaction with the bubble visualization is received. Responsive to receiving the interaction, the bubble visualization is updated by adjusting the bubble to include a radial bar graph representative of a relative quantity of each distinct value of the concept represented by the bubble at each indicator of the plurality of indicators.
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:
Grant
Filed:
November 11, 2016
Date of Patent:
February 4, 2020
Assignee:
Merck Sharp & Dohme Corp.
Inventors:
Thomas H. Graham, Tao Yu, Sherman T. Waddell, John A. McCauley, Andrew Stamford, Wensheng Liu, Jay A. Grobler, Libo Xu
Abstract: Phosphate-based linkers with tunable stability for intracellular delivery of drug conjugates are described. The phosphate-based linkers comprise a monophosphate, diphosphate, triphosphate, or tetraphosphate group (phosphate group) and a linker arm comprising a tuning element and optionally a spacer. A payload is covalently linked to the phosphate group at the distal end of the linker arm and the functional group at the proximal end of the linker arm is covalently linked to a cell-specific targeting ligand such as an antibody. These phosphate-based linkers have a differentiated and tunable stability in blood vs. an intracellular environment (e.g. lysosomal compartment).
Type:
Grant
Filed:
March 30, 2015
Date of Patent:
February 4, 2020
Assignees:
Merck Sharp & Dohme Corp., Ambrx, Inc.
Inventors:
Robert M. Garbaccio, Jeffrey Kern, Philip E. Brandish, Sanjiv Shah, Linda Liang, Ying Sun, Jianing Wang, Nick Knudsen, Andrew Beck, Anthony Manibusan, Dennis Gately
Abstract: The present invention is directed to processes for preparing beta 3 agonists of Formula (I) and Formula (II) and their intermediates. The beta 3 agonists are useful in the treatment of certain disorders, including overactive bladder, urinary incontinence, and urinary urgency.
Type:
Application
Filed:
October 1, 2019
Publication date:
January 30, 2020
Applicant:
Merck Sharp & Dohme Corp.
Inventors:
John Y.L. CHUNG, Kevin CAMPOS, Edward CLEATOR, Robert F. DUNN, Andrew GIBSON, R. Scott HOERRNER, Stephen KEEN, Dave LIEBERMAN, Zhuqing LIU, Joseph LYNCH, Kevin M. MALONEY, Feng XU, Nobuyoshi YASUDA, Naoki YOSHIKAWA, Yong-Li ZHONG
Abstract: This disclosure relates to a method for estimating a particle size distribution (PSD) and a morphology for a set of particles. A computer system receives a plurality of chord length distributions (CLDs) of different types for a set of particles. The computer system then estimates a morphology for the set of particles based on the plurality of received CLDs. The computer system also identifies a plurality of descriptors of the plurality of CLDs for the set of particles based on the plurality of received CLDs. The computer system then estimates metrics for the PSD for the set of particles based on the plurality of identified CLD descriptors. Based on the estimated PSD metrics for the set of particles, the computer system generates an estimate of the PSD for the set of particles. Finally, the computer system outputs the estimated morphology and the estimated PSD for the set of particles.
Abstract: The present invention relates to spirocyclic quinolizine derivatives and pharmaceutically acceptable salts or prodrug thereof, compositions comprising at least one spirocyclic quinolizine derivative, and methods of using the spirocyclic quinolizine derivatives for treating or preventing HIV infection in a subject.
Type:
Grant
Filed:
December 12, 2016
Date of Patent:
January 28, 2020
Assignee:
Merck Sharp & Dohme Corp.
Inventors:
Yonglian Zhang, Sherman T. Waddell, Tao Yu, John A. McCauley, Andrew Stamford
Abstract: The present invention relates to a drug delivery device comprising a drug container having at least one bellow. The at least one bellow has a first surface and an opposing second surface. The first surface is comprised of a first Belleville spring and the opposing second surface is comprised of a second Belleville spring, wherein the second Belleville spring has a higher spring rate than the first Belleville spring.
Type:
Grant
Filed:
June 1, 2015
Date of Patent:
January 28, 2020
Assignee:
Merck Sharp & Dohme Corp.
Inventors:
Peter A. Basile, Steven Carl Persak, Mikhail Gotliboym
Abstract: The present invention relates to metallo-?-lactamase inhibitor compounds of Formula I: and pharmaceutically acceptable salts thereof, wherein Z, RA, X1, X2 and R1 are as defined herein. The present invention also relates to compositions which comprise a metallo-?-lactamase inhibitor compound of the invention or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, optionally in combination with a beta lactam antibiotic and/or a beta-lactamase inhibitor. The invention further relates to methods for treating a bacterial infection comprising administering to a patient a therapeutically effective amount of a compound of the invention, in combination with a therapeutically effective amount of one or more ?-lactam antibiotics and optionally in combination with one or more beta-lactamase inhibitor compounds. The compounds of the invention are useful in the methods described herein for overcoming antibiotic resistance.
Type:
Grant
Filed:
January 10, 2019
Date of Patent:
January 28, 2020
Assignee:
Merck Sharp & Dohme Corp.
Inventors:
Frank Bennett, Jinlong Jiang, Alexander Pasternak, Shuzhi Dong, Xin Gu, Jack D. Scott, Haiqun Tang, Zhiqiang Zhao, Yuhua Huang, Dexi Yang, Katherine Young, Li Xiao, Zhibo Zhang, Jianmin Fu
Abstract: The present invention provides multispecific molecules, e.g., comprising more than one ISVD or Nanobody, that bind to PD1 and CTLA4. These molecules have been engineered so as to reduce the incidence of binding by pre-existing antibodies in the bodies of a subject administered such a molecule. Methods for increasing immune response, treating cancer and/or treating an infectious disease with such molecules are provided.
Type:
Grant
Filed:
November 17, 2016
Date of Patent:
January 28, 2020
Assignee:
Merck Sharp & Dohme Corp.
Inventors:
Juha Punnonen, Edward Bowman, Maribel Beaumont, Marie-Ange Buyse, Carlo Boutton, Bruno Dombrecht, Bjorn Victor, David Vlerick, Robert A. Kastelein
Abstract: The instant invention provides compounds of formula (I) which are PI3K-delta inhibitors, and as such are useful for the treatment of PI3K-delta-mediated diseases such as inflammation, asthma, COPD and cancer.
Type:
Grant
Filed:
March 24, 2017
Date of Patent:
January 28, 2020
Assignee:
Merck Sharp & Dohme Corp.
Inventors:
Abdelghani Abe Achab, Matthew P. Christopher, Francesc Xavier Fradera Llinas, Jason D. Katz, Joey L. Methot, Hua Zhou, Shimin Xu, Jianmin Fu, Ning Fu, Yabin Li, Xichao Wang
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:
Grant
Filed:
December 12, 2016
Date of Patent:
January 21, 2020
Assignee:
Merck Sharp & Dohme Corp.
Inventors:
Yongxin Han, Abdelghani Achab, Purakkattle Biju, Yongqi Deng, Xavier Fradera, Liangqin Guo, Shuwen He, Joseph Kozlowski, Ravi Kurukulasuriya, Kun Liu, Meredeth Ann McGowan, Qinglin Pu, Nunzio Sciammetta, Hongjun Zhang, Hua Zhou
Abstract: 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:
Grant
Filed:
February 10, 2017
Date of Patent:
January 21, 2020
Assignee:
Merck Sharp & Dohme Corp.
Inventors:
Daria Hazuda, Michael D. Miller, Jay A. Grobler, Deborah Anne Nicoll-Griffith
Abstract: The present invention provides genetic markers on human chromosome 6 that are associated with a beneficial response to a treatment that targets Clostridium difficile (C. difficile) toxin B (TcdB), e.g. a TcdB antibody. These TcdB treatment response markers are useful, inter alia, to identify patients who are most likely to benefit from treatment with a treatment that 5 targets TcdB in methods of treating patients having a disease susceptible to treatment with a TcdB antibody, and in methods for selecting the most appropriate therapy for such patients. The invention also provides antibodies, drug products, and kits useful with the TcdB Treatment response markers of the invention.
Type:
Application
Filed:
December 7, 2017
Publication date:
January 16, 2020
Applicants:
Merck Sharp & Dohme Corp., Beijing Genomics Institute at Shenzhen
Inventors:
Peter M. Shaw, Devan V. Mehrotra, Rebecca L. Blanchard, Judong Shen, Robin Mogg, Mary Beth Dorr, Junhua Li, Xun Xu
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:
Application
Filed:
December 1, 2017
Publication date:
January 16, 2020
Applicant:
Merck Sharp & Dohme Corp.
Inventors:
Thomas H. Graham, Tao Yu, Sherman T. Waddell, John A. McCauley
Abstract: Disclosed herein is a method for inhibiting expression of a gene of a subject comprising administering (1) a composition comprising R-(L)a-(G)b; wherein R is an oligonucleotide selected from the group consisting of DNA, RNA, siRNA, and microRNA; L is a linker and each occurrence of L is independently selected from Table 3; G is a targeting ligand and each occurrence of G is independently selected from Table 4; each of a and b is independently 0, 1, 2, 3 or 4; and (2) a composition comprising (P)c-(L)d-(G)e; wherein P is a peptide and each occurrence of P is independently selected from Table 2; L is a linker and each occurrence of L is independently selected from Table 3; G is a targeting ligand and each occurrence of G is independently selected from Table 4; d is 0, 1, 2, 3, 4, 5 or 6; and each of c and e is independently 1, 2, 3, 4, 5 or 6. Compositions in (1) and (2) can be co-administered or sequentially administered.
Type:
Grant
Filed:
May 8, 2018
Date of Patent:
January 14, 2020
Assignee:
Merck Sharp & Dohme Corp.
Inventors:
Steven L. Colletti, Thomas J. Tucker, David M. Tellers, Boyoung Kim, Rob Burke, Kathleen B. Calati, Matthew G. Stanton, Rubina G. Parmar, Jeffrey G. Aaronson, Weimin Wang
Abstract: The present invention relates to oxazolidinone Compounds of Formula (I): (I) and pharmaceutically acceptable salts thereof, wherein A, E, and R1 are as defined herein. The present invention also relates to compositions which comprise at least one oxazolidinone compound of the invention. The invention also provides methods for inhibiting growth of mycobacterial cells as well as a method of treating mycobacterial infections by Mycobacterium tuberculosis comprising administering a therapeutically effective amount of an oxazolidinone of the invention and/or a pharmaceutically acceptable salt thereof, or a composition comprising such compound and/or salt.