Abstract: The present invention relates to efficient processes useful in the preparation of fluorinated nucleosides, such as (2S,3R,4S,5R)-5-(2-amino-6-oxo-1,6-dihydro-9H-purin-9-yl)-3-fluoro-4-hydroxy-2-(mercaptomethyl)tetrahydrofuran-3-yl dihydrogen phosphate, also known as 3?-fluoro-thio-guanosine monophosphate or 3?-F-thio-GMP. Such fluorinated nucleosides may be useful as a biologically active compound and or as an intermediate for the synthesis of more complex biologically active compounds. The present invention also encompasses intermediates useful in the disclosed synthetic processes and the methods of their preparation.
Type:
Application
Filed:
May 20, 2021
Publication date:
June 8, 2023
Applicant:
Merck Sharp & Dohme LLC
Inventors:
Travis Armiger, Kevin M. Belyk, Tamas Benkovics, Cheol K. Chung, Yining Ji Chen, Heather Claire Johnson, Artis Klapars, Zhijian Liu, Zhuqing Liu, Jeffrey C. Moore, Andrew J. Neel, Feng Peng, Stephan M. Rummelt, Nastaran Salehi Marzuarani, Benjamin D. Sherry, Zhiguo Jake Song, Ben William Hulme Turnbull, Lu Wang, Feng Xu
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 XI activation inhibitors.
Type:
Application
Filed:
May 7, 2021
Publication date:
June 1, 2023
Applicant:
Merck Sharp & Dohme LLC
Inventors:
Jacqueline D. HICKS, John S. Debenham, Amjad Ali, Ying-Duo Gao, Lan Wei, Dexi Yang, Rongze Kuang, Alan Hruza, Peter Nizner, Daniel A. Tatosian
Abstract: Antibodies that bind the apple 3 domain of human coagulation Factor XI and inhibit activation of FXI by coagulation factor XIIa as well as activation of FIX by FXIa are described.
Type:
Grant
Filed:
May 1, 2020
Date of Patent:
May 30, 2023
Assignees:
Merck Sharp & Dohme LLC, Adimab, LLC
Inventors:
Zhu Chen, Kenneth Ellsworth, James Milligan, Elizabeth Oldham, Dietmar Seiffert, Vaishnavi Ganti, Mohammad Tabrizifard, Bianka Prinz
Abstract: Described herein are compounds of Formula I: or a pharmaceutically acceptable salt thereof, wherein A, R1, R2, R3, W, X, Y, Z, m, n and p are as defined herein. The compounds of Formula I act as RIPK1 inhibitors and can be useful in preventing, treating or acting as a remedial agent for RIPK1-related diseases.
Type:
Application
Filed:
October 25, 2022
Publication date:
May 25, 2023
Applicant:
Merck Sharp & Dohme LLC
Inventors:
Abdelghani Abe Achab, Zachary G. Brill, Jenny Lorena Rico Duque, Xavier Fradera, Joey L. Methot, Phieng Siliphaivanh, Jing Su, Brandon A. Vara, Erin F. DiMauro
Abstract: The present invention relates to monobactam compounds of Formula I: and pharmaceutically acceptable salts thereof. The present invention also relates to compositions which comprise a monobactam compound of structural formula I or a pharmaceutically acceptable salt therof, 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 structural formula I, either alone or in combination with a therapeutically effective amount of a second beta-lactam antibiotic.
Type:
Application
Filed:
November 16, 2022
Publication date:
May 25, 2023
Applicant:
Merck Sharp & Dohme LLC
Inventors:
Helen Y. Chen, Shuzhi Dong, Zhiyong Hu, Jing Su, Tao Yu, Yong Zhang
Abstract: In its many embodiments, the present invention provides certain substituted aryl and heteroaryl ether compounds of the Formula (I): and pharmaceutically acceptable salts thereof, wherein X, R1, R2, R3, L, R4, L1, Q, and R5 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:
Grant
Filed:
October 9, 2017
Date of Patent:
May 23, 2023
Assignee:
Merck Sharp & Dohme LLC
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, Bin Zhu
Abstract: This invention relates to novel implant drug delivery systems for long-acting delivery of antiviral and contraceptive drugs. These compositions are useful for the treatment or prevention of human immunodeficiency virus (HIV) infection and the prevention of pregnancy.
Type:
Application
Filed:
April 30, 2021
Publication date:
May 18, 2023
Applicant:
Merck Sharp & Dohme LLC
Inventors:
Morgan B. Giles, Seth P. Forster, Stephanie Elizabeth Barrett, Athanas Koynov, Ryan S. Teller
Abstract: The present invention provides molecules, such as ISVDs and Nanobodies, that bind to CTLA4 or human serum albumin. 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 27, 2019
Date of Patent:
May 16, 2023
Assignee:
Merck Sharp & Dohme LLC
Inventors:
Juha Punnonen, Maribel Beaumont, Marie-Ange Buyse, Carlo Boutton, Bruno Dombrecht, Bjorn Victor, Robert A. Kastelein
Abstract: The present disclosure is directed to tetrahydroquinazoline derivatives of Formula I and their use for selectively killing HIV infected GAG-POL expressing cells without concomitant cytotoxicity to HIV naïve cells, and for the treatment or prophylaxis of infection by HIV, or for the treatment, prophylaxis or delay in the onset or progression of AIDS or AIDS Related Complex (ARC).
Type:
Grant
Filed:
August 25, 2021
Date of Patent:
May 16, 2023
Assignee:
Merck Sharp & Dohme LLC
Inventors:
Antonella Converso, Abdellatif El Marrouni, Anthony W. Shaw, David N. Hunter, Ashley Forster, Cheng Wang, Yunlong Zhang
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 XI activation inhibitors.
Type:
Application
Filed:
March 26, 2021
Publication date:
May 11, 2023
Applicant:
Merck Sharp & Dohme LLC
Inventors:
Jacqueline D. Hicks, Amjad Ali, John S. Debenham, Anthony Donofrio, Wenlang Fu, Ying-Duo Gao, Alan Hruza, Yeon-Hee Lim, Matthew J. Lombardo, Peter Nizner, Sung-Sau So, Zheng Tan, Daniel A. Tatosian, Dong Xiao, Dexi Yang, Yang Yu
Abstract: Phosphonate linkers and their use for delivering compounds with passive cell permeability into a cell wherein the phosphonate group facilitates cellular retention of the compound are described.
Type:
Application
Filed:
December 2, 2022
Publication date:
May 11, 2023
Applicant:
Merck Sharp & Dohme LLC
Inventors:
Robert M. Garbaccio, Jeffrey C. Kern, James J. Mulhearn, Philip E. Brandish
Abstract: The disclosure relates to stable RSV F proteins and immunogenic compositions containing the same, as well as methods of using the immunogenic compositions and compositions comprising the RSV F proteins.
Type:
Application
Filed:
December 20, 2022
Publication date:
May 11, 2023
Applicant:
Merck Sharp & Dohme LLC
Inventors:
Lan Zhang, Arthur Fridman, Eberhard Durr, Andrew Bett
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/or pneumococcal diseases caused by S. pneumoniae.
Type:
Grant
Filed:
December 17, 2019
Date of Patent:
May 9, 2023
Assignee:
Merck Sharp & Dohme LLC
Inventors:
Chitrananda Abeygunawardana, Yadong Adam Cui, Romulo Ferrero, Jian He, Luwy Musey, Tanaz Petigara, Julie M. Skinner
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:
December 18, 2020
Publication date:
May 4, 2023
Applicant:
MERCK SHARP & DOHME LLC
Inventors:
Abdelghani Abe Achab, Matthew L. Childers, Christian Fischer, Symon Gathiaka, Derun Li, Min Lu, Anandan Palani, Rachel L. Palte, Qinglin Pu, David L. Sloman, Hongjun Zhang
Abstract: Provided are 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. Also provided are uses of the compounds of Formula (I), as defined herein, 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:
Application
Filed:
February 2, 2021
Publication date:
May 4, 2023
Applicants:
Merck Sharp & Dohme LLC, The Walter and Eliza Hall Institute of Medical Research, MSD R&D (China) Co., Ltd.
Inventors:
Manuel de Lera Ruiz, Paola Favuzza, Zhuyan Guo, Bin Hu, Michael J. Kelly, III, Zhiyu Lei, John A. McCauley, David B. Olsen, Brad Sleebs, Tony Triglia, Dongmei Zhan, Lianyun Zhao
Abstract: The present disclosure provides, among other things, a pharmaceutical composition that includes a lipid nanoparticle adjuvant and an anti-human papillomavirus (HPV) comprising HPV virus-like particles (VLPs) of at least one type of human papillomavirus (HPV) selected from the group consisting of HPV types: 6, 11, 16, 18, 26, 31, 33, 35, 39, 45, 51, 52, 53, 55, 56, 58, 59, 66, 68, 73, and 82.
Type:
Grant
Filed:
February 9, 2021
Date of Patent:
May 2, 2023
Assignee:
Merck Sharp & Dohme LLC
Inventors:
Andrew J. Bett, John P. Bilello, Amy S. Espeseth, Tong-Ming Fu, Marian E. Gindy
Abstract: The present invention provides processes for the preparation of sugammadex: (I) In one aspect, there is provided a process for the preparation of sugammadex from 8-per-deoxy-8-bromo-?-cyclodextrin and 3-mercaptopropionic acid. In another aspect, there is provided an alternative process for the preparation of sugammadex from 8-per-deoxy-8-bromo-?-cyclodextrin and disodium 3 -mercaptopropionate. In another aspect, there is provided a process for the preparation of 8-per-deoxy-8-bromo-?-cyclod extrin, which may be used in the production of sugammadex. In one such aspect, there is provided a process for the preparation of 8-per-deoxy-8-bromo-y-cyclodextrin from ?-cyclodextrin and a brominating agent. In another such aspect, there is provided a process for the preparation of 8-per-deoxy-8-bromo-?-cyclodextrin comprising, inter alia, reacting ?-cyclodextrin with an electrophilic brominating agent, a deoxygenating agent, and an acid in the presence of an organic solvent.
Type:
Grant
Filed:
June 3, 2019
Date of Patent:
April 25, 2023
Assignee:
Merck Sharp & Dohme LLC
Inventors:
Jamie M. McCabe Dunn, Nadine Kuhl, Wenyong Chen, Yang Cao, Donald R. Gauthier, Jr., Alan Michael Hyde, Susan L. Zultanski
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:
Grant
Filed:
May 1, 2018
Date of Patent:
April 25, 2023
Assignee:
Merck Sharp & Dohme LLC
Inventors:
Manoj K. Sharma, Wendy Benjamin, Sarita Mittal, Ashwin Basarkar, Chakravarthy Nachu Narasimhan, Ramesh S. Kashi, Mohammed Shameem, Soumendu Bhattacharya, Yogita Krishnamachari
Abstract: The present disclosure provides, among other things, a lipid nanoparticle adjuvant composition. The present disclosure provides pharmaceutical compositions that include a stable lipid nanoparticle adjuvant and human papillomavirus (HPV) virus-like particles (VLPs) of at least one type of human papillomavirus (HPV) selected from the group consisting of HPV types: 6, 11, 16, 18, 26, 31, 33, 35, 39, 45, 51, 52, 53, 55, 56, 58, 59, 66, 68, 73, and 82.
Type:
Application
Filed:
August 17, 2022
Publication date:
April 20, 2023
Applicant:
Merck Sharp & Dohme LLC
Inventors:
Andrew Bett, Izzat T. Raheem, Jason W. Skudlarek, Erica L. Strable
Abstract: The present disclosure provides, among other things, a pharmaceutical composition that includes a lipid nanoparticle adjuvant and an anti-human papillomavirus (HPV) comprising HPV virus-like particles (VLPs) of at least one type of human papillomavirus (HPV) selected from the group consisting of HPV types: 6, 11, 16, 18, 26, 31, 33, 35, 39, 45, 51, 52, 53, 55, 56, 58, 59, 66, 68, 73, and 82.
Type:
Application
Filed:
February 9, 2021
Publication date:
April 20, 2023
Applicant:
Merck Sharp & Dohme LLC
Inventors:
Marian E. Gindy, John P. Bilello, Amy S. Espeseth, Andrew J. Bett, Tong-Ming Fu