Patents Assigned to Merck Sharp & Dohme LLC
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Publication number: 20240226439Abstract: A method of controlling a temperature of a biopharmaceutical product during blow-fill sealing, includes developing a model based on heat transfer mechanisms that incorporates the effects of the blow-fill sealing on the biopharmaceutical product, providing a parison to a blow-fill sealing machine for accepting the biopharmaceutical product during the blow-fill sealing, predicting a temperature of at least one the biopharmaceutical product, the parison, and a component of the blow-fill sealing machine at a stage in the blow-fill sealing, and adjusting a parameter of the blow-fill sealing machine to reduce damage to the biopharmaceutical product.Type: ApplicationFiled: October 11, 2023Publication date: July 11, 2024Applicant: Merck Sharp & Dohme LLCInventors: Carl Chew, Matthew H. Flamm, Jeremy A. Haddock, Rikhabh Jain, Atul Karande, Brit L. Rudeen
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N-heteroaryl indazole derivatives as LRRK2 inhibitors, pharmaceutical compositions, and uses thereof
Patent number: 12030872Abstract: The present invention is directed to substituted certain N-heteroaryl indazole 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 diseases, such as Parkinson's disease, in which LRRK-2 kinase is involved.Type: GrantFiled: October 25, 2019Date of Patent: July 9, 2024Assignee: Merck Sharp & Dohme LLCInventors: Vladimir Simov, William P. Kaplan, John J. Acton, III, Michael J. Ardolino, Joanna L Chen, Peter H. Fuller, Hakan Gunaydin, Derun Li, Ping Liu, Kaitlyn Marie Logan, Joey Methot, Gregori J. Morriello, Santhosh F. Neelamkavil, Luis Torres, Xin Yan, Hua Zhou -
Publication number: 20240218009Abstract: Novel forms of 2-amino-9-[(2R,5R,7R,8S,10R,12aR, 14R,15S,15aR,16R)-14-(6-amino-9H-purin-9-yl)-15,16-difluoro-2,10-dihydroxy-2,10-disulfidooctahydro-12H-5,8-methanofuro[3,2-1][1,3,6,9,11,2,10]pentaoxadiphospha-cyclotetradecin-7-yl]-1,9-dihydro-6H-purin-6-one, which include adducts of 2-amino-9-[(2R,5R,7R,8S,10R,12aR, 14R,15S,15aR,16R)-14-(6-amino-9H-purin-9-yl)-15,16-difluoro-2,10-dihydroxy-2,10-disulfidooctahydro-12H-5,8-methanofuro[3,2-1][1,3,6,9,11,2,10]pentaoxadiphospha-cyclotetradecin-7-yl]-1,9-dihydro-6H-purin-6-one and L-histidine, may be useful as inductors of type I interferon production, specifically as STING active agents.Type: ApplicationFiled: April 18, 2022Publication date: July 4, 2024Applicant: Merck Sharp & Dohme LLCInventors: Stephanus Axnanda, Andrew Patrick Jude Brunskill, Erin N. Guidry, Eric A. Kemp, Courtney K. Maguire, Mikhail Reibarkh, Matthew S. Winston
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Publication number: 20240208958Abstract: The present invention relates to the oxazolidinone compound of Formula (I): and pharmaceutically acceptable salts thereof. The present invention also relates to compositions containing the compound of Formula (I). The invention also provides methods for inhibiting growth of mycobacterial cells as well as a method of treating mycobacterial infections by Mycobacterium tuberculosis by administering a therapeutically effective amount of Formula (I) and/or a pharmaceutically acceptable salt thereof, or a composition comprising such compound and/or salt.Type: ApplicationFiled: March 20, 2021Publication date: June 27, 2024Applicant: Merck Sharp & Dohme LLCInventors: Brendan M. CROWLEY, Philippe NANTERMET, David B. OLSEN, Takao SUZUKI, Lihu YANG, Lanying YOU
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Publication number: 20240208987Abstract: The present disclosure is directed to linker-payloads, and salts (including pharmaceutically acceptable salts), solvates, or stereoisomers thereof, comprising a structure of formula I: The disclosure is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds, intermediates thereof, and compositions in the prevention or treatment of cancers and/or tumors.Type: ApplicationFiled: October 23, 2023Publication date: June 27, 2024Applicant: Merck Sharp & Dohme LLCInventors: Vlad Bacauanu, Manoj B. Charati, Sijie Chen, Rebecca Elizabeth Johnson, Simon B. Lang, Christian L. Morales, Ryan Quiroz, W. Michael Seganish, Nancy Zepeda
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Publication number: 20240208986Abstract: Described herein are compounds of Formula I: (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: ApplicationFiled: April 21, 2022Publication date: June 27, 2024Applicant: Merck Sharp & Dohme LLCInventors: Joanna L. Chen, Erin F. DiMauro, Kevin D. Dykstra, Xavier Fradera, Peter H. Fuller, Charles A. Lesburg, Min Lu, Joey L. Methot, Matthew J. Mitcheltree, Jing Su
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Publication number: 20240208994Abstract: 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 degeneration, diabetic macular edema, diabetic retinopathy and retinal vein occlusion. The compounds are selective inhibitors of plasma kallikrein.Type: ApplicationFiled: April 18, 2022Publication date: June 27, 2024Applicant: Merck Sharp & Dohme LLCInventors: Alan C. Cheng, Ying-Duo Gao, Song Yang, Mihir Mandal, Jiafang He, Jovan Alexander Lopez, Maoqun Tian
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Publication number: 20240207425Abstract: The present disclosure is directed to linker-payloads, and pharmaceutically acceptable salts, solvates, or stereoisomer thereof, comprising a structure of formula I: The disclosure is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds, intermediates thereof, and compositions in the prevention or treatment of cancers and/or tumors.Type: ApplicationFiled: December 12, 2023Publication date: June 27, 2024Applicant: Merck Sharp & Dohme LLCInventors: Manoj B. Charati, John A. Flygare, Rebecca Elizabeth Johnson, Simon B. Lang, W. Michael Seganish
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Patent number: 12016914Abstract: 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. 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: GrantFiled: March 23, 2023Date of Patent: June 25, 2024Assignee: Merck Sharp & Dohme LLCInventors: Chitrananda Abeygunawardana, Yadong Adam Cui, Romulo Ferrero, Jian He, Luwy Musey, Tanaz Petigara, Julie M. Skinner
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Patent number: 12016330Abstract: Container system and method for freezing (and subsequently thawing) a liquid such as a drug substance, such that all containers in a set have a uniform width, hence uniform freeze-path length, in the widthwise direction and perpendicular to major walls of the containers, irrespective of the particular length, height, and volumetric capacity of the various containers in the set. This leads to uniform freezing performance and thereby reduces cryoconcentration. The system also eliminates or reduces ice-bridging, and the potential for containers rupturing during freezing and thawing operations.Type: GrantFiled: December 8, 2021Date of Patent: June 25, 2024Assignee: Merck Sharp & Dohme LLCInventors: Jeffrey Charles Johnson, Anthony Flammino, Mark Anton Petrich, Scott McFeaters, John H. Roosa, Jr., Robert Ian Alpern, Joseph W. Locurcio, Matthew H. Flamm
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Publication number: 20240199680Abstract: The present invention relates to efficient processes useful in the preparation of fluorinated cyclic dinucleosides, such as [P(R)]-2?-deoxy-2?-fluoro-5?-O—[(R)-hydroxymercaptophosphinyl]-P-thio-?-D-arabino-adenylyl-(3??5?)-3?-deoxy-3?-fluoroguanosine cyclic nucleotide, which is also known as (2R,5R,7R,8S,10R,12aR,14R,15S,15aR,16R)-7-(2-amino-6-oxo-1,6-dihydro-9H-purin-9-yl)-14-(6-amino-9H-purin-9-yl)-15,16-difluoro-2, 10-bis(sulfanyl)octahydro-2H,10H, 12H-2?5,10?5-5,8-methanofuro[3,2-1][1, 3,6,9,11,2,10]pentaoxadiphosphacyclotetradecine-2,10-dione. The present invention also encompasses intermediates useful in the disclosed synthetic processes and the methods of their preparation.Type: ApplicationFiled: March 28, 2022Publication date: June 20, 2024Applicant: Merck Sharp & Dohme LLCInventors: Chihui An, Patrick S. Fier, Kaori Hiraga, Zhijian Liu, Nicholas M. Marshall, John McIntosh, Steven P. Miller, Jeffrey C. Moore, Grant S. Murphy, Jennifer V. Obligacion, Weilan Pan, Feng Peng, Nastaran Salehi Marzijarani, Matthew S. Winston
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Publication number: 20240200099Abstract: Rotavirus vectors encoding in their genome a heterologous gene, and nucleic acid constructs encoding such rotavirus vectors. The rotavirus vector genome may include a rotavirus non-structural protein, a 2A peptide downstream of the rotavirus non-structural protein, and a heterologous protein downstream of the 2A peptide. The heterologous gene may be, for example, a SARS-CoV-2 spike protein or a fragment thereof, or an RSV F protein or a fragment thereof.Type: ApplicationFiled: April 11, 2022Publication date: June 20, 2024Applicant: Merck Sharp & Dohme LLCInventors: Dai Wang, Jiajie Wei
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Publication number: 20240190892Abstract: 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 degeneration, diabetic macular edema, diabetic retinopathy and retinal vein occlusion. The compounds are selective inhibitors of plasma kallikrein.Type: ApplicationFiled: March 16, 2022Publication date: June 13, 2024Applicant: Merck Sharp & Dohme LLCInventors: Natalija Cernaka, Anthony K. Ogawa, Alan C. Cheng, Jianming Bao, Phillip Patrick Sharp, Jovan Alexander Lopez, Dong Xiao, Haiqun Tang
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Patent number: 12005072Abstract: The instant invention relates to a method for reducing the risk for development of anti-viral treatment resistance due to an HIV mutation in a human subject infected with HIV, comprising administering EFdA in combination with one or more anti-viral agents.Type: GrantFiled: July 12, 2019Date of Patent: June 11, 2024Assignee: Merck Sharp & Dohme LLCInventors: Daria Jean Hazuda, Ming-Tain Lai
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Patent number: 12009060Abstract: A BGC prediction system identifies candidate biosynthetic gene clusters (BGCs) within genomes using machine-learned models, such as a shallow neural network and recurrent neural network (RNN). A set of domains within a genome sequence are identified, each domain corresponds to a set of domain identifiers. A shallow neural network block is applied to each set of domain identifiers to produce a set of vectors. An RNN block is applied to the set of vectors to produce a BGC class score for each domain. The RNN block was trained using an identified set of positive vectors, which represents known BGCs, and a synthesized set of negative vectors, which is unlikely to represent BGCs. Candidate BGCs are selected by averaging BGC class scores across genes within a domain and comparing the average BGC class scores to a threshold. The candidate BGCs are provided for display on a user interface.Type: GrantFiled: March 22, 2019Date of Patent: June 11, 2024Assignees: Merck Sharp & Dohme LLC, MSD Czech Republic s.r.o.Inventors: Geoffrey D. Hannigan, David Prihoda, Jindrich Soukup, Christopher Harron Woelk, Danny A. Bitton
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Publication number: 20240182511Abstract: Novel forms of 2-amino-9-[(2R,5R,7R,8S,10R,12aR,14R,15S,15aR,16R)-14-(6-amino-9H-purin-9)-yl)-15,16-difluoro-2,10-dihydroxy-2,10-disulfidooctahydro-12H-5.8-methanofuro[3,2-1][1,3,6,9,11,2,10]pentaoxa-diphosphacyclotetradecin-7-yl]-1,9-dihydro-6H-purin-6-one, which include crystalline salts and hydrates of 2-amino-9)-[(2R,5R,7R,8,S,10R,12aR,14R,15S,15aR,16R)-14-(6-amino-9H-purin-9-yl)-15,16-difluoro-2,10-dihydroxy-2,10-disulfido-octahydro-12H-5,8-methanofuro[3,2-1][1,3,6,9,11,2,10]pentaoxa-diphosphacyclotetradecin-7-yl]-1,9-dihydro-6H-purin-6-one, may be useful as inductors of type I interferon production, specifically as STING active agents.Type: ApplicationFiled: April 4, 2022Publication date: June 6, 2024Applicant: Merck Sharp & Dohme LLCInventors: Stephanus Axnanda, Zachary E. Dance, David J. Lamberto, Zhijian Liu, Feng Peng, Marc Poirier, Matthew S. Winston
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Publication number: 20240182573Abstract: The present invention relates to stable formulations of antibodies against T cell immunoreceptor with Ig and ITIM domains (TIGIT), optionally further containing an anti-human programmed death receptor 1 (PD-1) antibody or antigen binding fragment thereof. Also provided are methods of treating various cancers and chronic infections with the formulations of the invention.Type: ApplicationFiled: January 25, 2024Publication date: June 6, 2024Applicant: Merck Sharp & Dohme LLCInventors: Arnab De, Chakravarthy Nachu Narasimhan
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Patent number: 12002202Abstract: Methods and systems are described for image segmentation. A machine learning model is applied to a set of images to generate results. The results may be obtained as a probability map for each image in the set of images. The model may be trained by accessing a set of labeled images, each image associated with a label indicating a location of a feature within a respective image. An initial set of parameters is accessed. An encoder is initialized with the initial set of parameters. The encoder is applied to the set of labeled images to generate a prediction of a feature location within each image. The initial set of parameters are updated based on the predictions and the label associated with the labeled images. The updated set of parameters and an additional set of parameters generated using a set of unlabeled images are aggregated.Type: GrantFiled: August 9, 2021Date of Patent: June 4, 2024Assignee: Merck Sharp & Dohme LLCInventors: Dani Kiyasseh, Antong Chen, Albert Joseph Swiston, Jr., Ronghua Chen
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Publication number: 20240174679Abstract: The present invention is directed to certain (hetero)aroyl 4-aminopyrazole derivatives of Formula (I) and pharmaceutically acceptable salts thereof, wherein A, R1, R2, and R3 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: ApplicationFiled: March 14, 2022Publication date: May 30, 2024Applicant: Merck Sharp & Dohme LLCInventors: Kaleen Konrad Childers, J. Michael Ellis, Peter J. Fuller, Hakan Gunaydin, Jack D. Scott, Haiqun Tang, Charles S. Yeung
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Patent number: 11995593Abstract: An adaptive risk management application retrieves data corresponding to an asset. The asset is a computing device or software application of an enterprise system. The adaptive risk management application identifies a set of vulnerabilities of the asset. The adaptive risk management application determines, for each identified vulnerability, a likelihood of a threat actor successfully exploiting the vulnerability. The adaptive risk management application determines, based on the likelihoods, a risk score for the asset. The adaptive risk management application sends the risk score for display.Type: GrantFiled: November 19, 2019Date of Patent: May 28, 2024Assignee: Merck Sharp & Dohme LLCInventors: Mark Joseph Risoldi, Sethuraman Balasubramanian
