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 one or more disease states that could benefit from inhibition of plasma kallikrein, including hereditary angioedema, uveitis, posterior uveitis, wet age related macular edema, diabetic macular edema, diabetic retinopathy and retinal vein occlusion. The compounds are selective inhibitors of plasma kallikrein.
Type:
Application
Filed:
November 18, 2021
Publication date:
January 25, 2024
Applicant:
Merck Sharp & Dohme LLC
Inventors:
Jianming Bao, Natalija Cernaka, Alan C. Cheng, Ying-Duo Gao, Salman Jabri, Jovan Alexander Lopez, Rohan Merchant, Anthony Ken Ogawa, Skylar K. Osler, Christopher J. Sinz, Phillip Patrick Sharp, Haiqun Tang, Maoqun Tian, Dong Xiao, Song Yang
Abstract: The present invention relates to methods for treating cancer in a patient comprising administering a PD-1 antagonist, e.g., an anti-PD-1 antibody or antigen binding fragment thereof (e.g. pembrolizumab), in specific amounts to the patient about every six weeks. In some embodiments, the amount of anti-PD-1 antibody or antigen binding fragment thereof is about 400 mg. In certain embodiments, the PD-1 antagonist is pembrolizumab, or an antigen binding fragment thereof. Also provided are compositions and kits comprising a dosage of an anti-PD-1 antibody, or antigen-binding fragment thereof, and uses thereof for treating cancer.
Abstract: An aseptic manifold dispensing assembly that comprises a connector for connecting to a source, a dispensing manifold in fluid communication with the connector that includes a plurality of outputs, and a filling manifold. The filling manifold comprises an inlet for connecting to at least one of the plurality of outputs of the dispensing manifold, a plurality of peristaltic pumps connected in parallel downstream the inlet, and a container downstream the plurality of peristaltic pumps, a scale, and a controller operatively connected to the scale and the filling manifold.
Type:
Application
Filed:
December 9, 2021
Publication date:
January 25, 2024
Applicant:
Merck Sharp & Dohme LLC
Inventors:
David J. Ostermayer, Marcus Skaflen, Edmond C. Menegaux, Robert Boulanger, Kelsey M. FitzGerald, Annette Krysiewicz, Paul M. Breza, Bogdan Tehlewicz, Abhay C. Kirpekar
Abstract: Described herein are compounds of Formula I or a pharmaceutically acceptable salt thereof. 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:
May 17, 2023
Publication date:
January 25, 2024
Applicant:
Merck Sharp & Dohme LLC
Inventors:
Joanna L. Chen, Yi-Heng Chen, Erin F. DiMauro, Min Liu, Joey L. Methot, Andrew J. Musacchio, Anandan Palani, Barbara Pio, Lorena Rico Duque, Phieng Siliphaivanh, Brandon A. Vara
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 influenza. The compounds are cap-dependent endonuclease inhibitors.
Type:
Application
Filed:
July 22, 2021
Publication date:
January 18, 2024
Applicants:
Merck Sharp & Dohme LLC, COCRYSTAL PHARMA, INC.
Inventors:
Yonglian Zhang, John A. McCauley, Michael Man-Chu Lo, Liangqin Guo, Kake Zhao, Frank Bennett, Ronald M. Kim, Reynalda Keh DeJesus, Valerie W. Shurtleff, Manuel de Lera Ruiz, Michael Plotkin, Hua Su, James Fells, Brendan M. Crowley, Harry R. Chobanian, Mark W. Embrey, Gregori J. Morriello
Abstract: 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 lysosomal storage diseases, neurodegenerative disease, cystic disease, cancer, or a diseases or disorders associated with elevated levels of glucosylceramide (GlcCer), glucosylsphingosine (GlcSph) and/or other glucosylceramide-based glycosphingolipids (GSLs).
Type:
Application
Filed:
September 15, 2021
Publication date:
January 18, 2024
Applicant:
Merck Sharp & Dohme LLC
Inventors:
Melissa C. Ford, Mark E. Fraley, Kristen L.G. Jones, H. Marie Loughran, James J. Mulhearn, Anthony J. Roecker, Kathy M. Schirripa, Ling Tong
Abstract: 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:
Grant
Filed:
July 14, 2022
Date of Patent:
January 16, 2024
Assignee:
Merck Sharp & Dohme LLC
Inventors:
Tinh Nguyen-DeMary, William James Ciolino
Abstract: The invention encompasses a process for densifying co-precipitated material comprised of an active pharmaceutical ingredient and at least one stabilizing excipient using thin film evaporation, and the densified co-precipitates made thereby. Bulk density and flowability of co-precipitates can be increased by processing the co-precipitated material using thin film evaporation.
Type:
Application
Filed:
July 7, 2023
Publication date:
January 11, 2024
Applicant:
Merck Sharp & Dohme LLC
Inventors:
Derek S. Frank, Haichen Nie, Luke Ryan Schenck, Jasmine M. Rowe
Abstract: The disclosure provides a novel process and synthetic intermediates for making belzutifan, a HIF-2a inhibitor, useful for the treatment of certain VHL-related indications and cancer.
Type:
Application
Filed:
July 3, 2023
Publication date:
January 11, 2024
Applicant:
Merck Sharp & Dohme LLC
Inventors:
Daniel A. DiRocco, Jackson Kenai Blender Cahn, Wai Ling Cheung-Lee, Stephanie W. Chun, J. Caleb Hethcox, Heather Claire Johnson, Jungchul Kim, Joshua N. Kolev, Birgit Kosjek, Diane Le, Scott D. McCann, John McIntosh, Jonathan P. McMullen, Jeffrey C. Moore, William Morris, Juan Esteban Velasquez Velez, Matthew S. Winston, Victoria Zhang, Yong-Li Zhong
Abstract: The present invention relates to methods for treating cancer comprising administering an antagonist of PD-1, e.g., anti-PD-1 antibody or antigen binding fragment thereof, and an anti-CTLA4 antibody or antigen binding fragment thereof, wherein the CTLA4 antibody or antigen binding fragment thereof is given at a fixed dose. Also provided are compositions and kits comprising a dosage of an anti-PD-1 antibody and a dosage of an anti-CTLA4 antibody, and uses thereof.
Type:
Application
Filed:
December 12, 2022
Publication date:
January 11, 2024
Applicant:
Merck Sharp & Dohme LLC
Inventors:
Blanca Homet Moreno, Nageatte Ibrahim, Scot W. Ebbinghaus, Lokesh Jain, Scott Diede
Abstract: A Saccharomyces cerevisiae antibody display system that simultaneously secrets and displays antibody fragments from a very large size synthetic nave human antibody library for therapeutic antibody lead discovery and engineering is described. A bait anchor complexed with a monovalent antibody fragment is tethered on the surface of the S. cerevisiae host cell, wherein the fragment can be assayed for antigen binding, while the full bivalent antibody is simultaneously secreted from the host cell. Methods of using the system for identifying antibodies from the library that bind specifically to an antigen of interest are also provided. Polypeptides, polynucleotides and host cells used for making the antibody display system are also provided along with methods of use thereof.
Abstract: A voltage-gated sodium channel expression system is described. The system comprises providing a polycistronic RNA message that encodes a polyprotein comprising a voltage-gated sodium channel alpha protein (Nav?) subunit and one or more voltage-gated sodium channel beta protein (Nav?) subunits, each of said subunits being separated by a 2A self-cleaving peptide. During translation, the polyprotein is cleaved into individual subunit proteins which can assemble into a voltage-gated sodium channel. Host cells and lipoparticles comprising the sodium channel expression system are also provided.
Abstract: A system and a method are disclosed for disconnecting clips. A clip separation tool includes two arms, the arms having jaws to receive connected clips at a distal end of the arms and handle portions on a proximal end for a user to engage the tool with his hand. A pivot mechanism is coupled to the arms, where, responsive to a force applied to the handle portions, the arms rotate relative to each other around the pivot mechanism such that the distal ends of the arms pivot away from one another and the proximal ends of the arms pivot towards one another. A spring biases the arms to rotate to an equilibrium position that is attained automatically under spring loading once the proximal ends of the arms are relieved of loading. The clip separation tool disconnects connected clips as the force causes the arms to rotate around the pivot mechanism.
Abstract: Apparatus and method for collecting a dried pharmaceutical product from a product reservoir of a pharmaceutical drying device, such as a thin film evaporator, while the product reservoir remains under continuous vacuum pressure.
Type:
Application
Filed:
December 2, 2021
Publication date:
January 4, 2024
Applicant:
MERCK SHARP & DOHME LLC
Inventors:
John H. Roosa, Frank D. Gianotti, III, Robert C. O'Connor, Luke Ryan Schenck, Matthew Yuhas, Jr.
Abstract: Arginase 1 binders that inhibit activity of hArg1, which comprise humanized anti-human Arginase 1 (hArg1) antibodies and antigen-binding fragments thereof obtained from mouse monoclonal antibodies comprising mouse VH and VL, are described. These Arginase 1 binders present an alternative mechanism for inhibiting hArg1 activity and highlight the ability to utilize binders as probes in the discovery and development of peptide and small molecule inhibitors for enzymes in general.
Type:
Application
Filed:
November 22, 2021
Publication date:
January 4, 2024
Applicant:
MERCK SHARP & DOHME LLC
Inventors:
Marc Andre Bailly, Kalyan Chakravarthy, Ghassan Najib Fayad, Laurence Fayadat-Dilman, Veronica Juan, Esther Kofman, Masahisa Handa, Jennifer E. O'Neil, Rachel Lynn Palte, Giovanna Scapin, Shahriar Shane Taremi
Abstract: Arginase 1 binders that inhibit the activity of human Arginase 1 (hArg1) and comprise human antibodies and antigen-binding fragments thereof comprising human VH and VL are described. These Arginase 1 binders present an alternative mechanism for inhibiting hArg1 activity and highlight the ability to utilize binders as probes in the discovery and development of peptide and small molecule inhibitors for enzymes in general.
Type:
Application
Filed:
November 22, 2021
Publication date:
January 4, 2024
Applicant:
MERCK SHARP & DOHME LLC
Inventors:
Marc Andre Bailly, Kalyan Chakravarthy, Ghassan Najib Fayad, Laurence Fayadat-Dilman, Esther Kofman, Masahisa Handa, Jennifer E. O'Neil, Rachel Lynn Palte, Giovanna Scapin, Shahriar Shane Taremi
Abstract: Antibodies and antigen-binding fragments thereof that bind the human voltage-gated sodium channel Nav1.7? protein subunit (Nav1.7 binders) are described. In particular embodiments, the Nav1.7 binders comprise a heavy-chain immunoglobulin single variable domain (ISVD or VHH).
Inventors:
Pravien Damitha Abeywickrema, Erik Depla, Bruno Dombrecht, Daniel M. Gorman, Andrea K. Houghton, Robert A. Kastelein, Richard L. Kraus, John Majercak, Kalyan Pande, Sujata Sharma
Abstract: A compact containment system comprises a mixing apparatus, a drying apparatus and a discharge apparatus. The mixing apparatus, which may be used to produce a slurry or solution mixture of solvent and dry powder during drug processing, comprises a dual compartment isolator for safely removing the dry powder from a dry powder container, a mixing vessel, and a negative cascading pressure controller. The drying apparatus comprises a drying unit, such as a thin film evaporator.
Type:
Application
Filed:
December 2, 2021
Publication date:
January 4, 2024
Applicant:
MERCK SHARP & DOHME LLC
Inventors:
John H. Roosa, Alan S. D'Alessandro, Frank D. Gianotti, III, Robert C. O'Connor, Luke Ryan Schenck, Timothy Stanoch, Matthew Yuhas, JR.
Abstract: The present invention is directed to 3-heteroaryl pyrrolidine and piperidine compounds which are agonists of orexin receptors. The present invention is also directed to uses of the compounds described herein in the potential treatment or prevention of neurological and psychiatric disorders and diseases in which orexin receptors are involved. The present invention is also directed to compositions comprising these compounds. The present invention is also directed to uses of these compositions in the potential prevention or treatment of such diseases in which orexin receptors are involved.
Type:
Application
Filed:
December 1, 2021
Publication date:
January 4, 2024
Applicant:
Merck Sharp & Dohme LLC
Inventors:
Stephane L. Bogen, Ping Chen, Dane James Claussen, Xianhai Huang, Michael T. Rudd, Shawn P. Walsh, Lan Wei, Dexi Yang