Abstract: The present invention relates to dosing regimens of an anti-LAG3 antibody useful for the treatment of cancer. In particular, the invention relates to the dosing regimen in a combination therapy which comprises administering an antibody of a Programmed Death 1 protein (PD-1) or Programmed Death Ligand 1 (PD-L1) and an antibody of Lymphocyte-Activation Gene 3 (LAG3). The invention also provides a method for treating cancer in a patient comprising administering to the patient an anti-LAG3 antibody and an anti-PD-1 antibody, wherein the tumor tissue section of the patient is PD-L 1 expression positive, and optionally LAG3 expression positive.
Type:
Application
Filed:
November 4, 2019
Publication date:
November 11, 2021
Applicant:
Merck Sharp & Dohme Corp.
Inventors:
Anson Kunjachan Abraham, Elliot K. Chartash, Kenneth Emancipator, Rosario Garrido, Jane Anne Healy, Jonathan W. Juco, Diane Levitan, Qing Zhao
Abstract: The present invention provides genetic markers on human chromosome 1 that are associated with a beneficial response to CRTH2 receptor antagonists. These CRTH2 receptor antagonist response markers are useful, inter alia, to identify patients who are most likely to benefit from treatment with CRTH2 receptor antagonist compositions and drug products, in methods of treating patients having a disease susceptible to treatment with a CRTH2 receptor antagonist, and in methods for selecting the most appropriate therapy for such patients.
Type:
Application
Filed:
July 16, 2021
Publication date:
November 11, 2021
Applicant:
Merck Sharp & Dohme Corp.
Inventors:
Gregory J. Opiteck, Peggy H. Wong, Joshua McElwee, Devan V. Mehrotra, Steven Greenberg, Zifang Guo
Abstract: The present invention provides molecules, such as ISVDs and Nanobodies, that bind to PD1 and LAG3 and, optionally to 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:
May 17, 2019
Date of Patent:
November 9, 2021
Assignee:
Merck Sharp & Dohme Corp.
Inventors:
Edward Bowman, Maribel Beaumont, Marie-Ange Buyse, Carlo Boutton, Bruno Dombrecht, Robert A. Kastelein, David Vlerick
Abstract: The present invention provides molecules, such as ISVDs and Nanobodies, that bind to PD1 and LAG3 and, optionally to 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:
May 17, 2019
Date of Patent:
November 9, 2021
Assignee:
Merck Sharp & Dohme Corp.
Inventors:
Edward Bowman, Maribel Beaumont, Marie-Ange Buyse, Carlo Boutton, Bruno Dombrecht, Robert A. Kastelein, David Vlerick
Abstract: The present disclosure provides Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) vaccines, recombinant vesicular stomatitis virus (VSV) vectors encoding the SARS-CoV-2 spike (S) protein or an immunogenic variant thereof, recombinant replicable VSV particles having a SARS-CoV-2 S protein or an immunogenic variant thereof on the surface of the particles, and immunogenic recombinant proteins comprising a SARS-CoV-2 S protein or a variant thereof. Immunogenic compositions comprising the SARS-CoV-2 vaccines, the recombinant VSV vectors, the recombinant replicable VSV particles and/or the immunogenic recombinant proteins may be used for inducing an immune response to the SARS-CoV-2, preventing infection by the SARS-CoV-2, vaccinating against the SARS-CoV-2 and/or producing adaptive mutants of the recombinant replicable VSV particles.
Type:
Application
Filed:
February 19, 2021
Publication date:
November 4, 2021
Applicants:
International AIDS Vaccine Initiative Inc., Merck Sharp & Dohme Corp.
Inventors:
Christopher Lee Parks, Maoli Yuan, Mark Feinberg, Amy Espeseth, Andrew J. Bett
Abstract: Interleukin-2 (IL-2) conjugates comprising at least one or more amino acid substitutions that bias binding to the IL-2 receptor ??c dimer over binding the IL-2 receptor ???c trimer and a non-natural amino acid at or near the N-terminus conjugated to a water-soluble polymer are described. The IL-2 conjugates are useful for treatment and prevention of cell proliferation and cancer in a patient.
Type:
Application
Filed:
April 20, 2021
Publication date:
November 4, 2021
Applicant:
Merck Sharp & Dohme Corp.
Inventors:
Cristina Abrahams, Edward Bowman, Xiaofan Li, Songnian Lin, Willy Solis, Ryan Stafford, Aarron Willingham, Alice Yam, Junhao Yang, Gang Yin
Abstract: The present invention relates to a compound represented by formula (I): and pharmaceutically acceptable salts thereof are disclosed as useful for treating or preventing diabetes, hyperlipidemia, obesity, NASH, inflammation related disorders, and related diseases and conditions. The compounds are useful as agonists of the G-protein coupled receptor GPR120. Pharmaceutical compositions and methods of treatment are also included.
Type:
Grant
Filed:
July 22, 2020
Date of Patent:
November 2, 2021
Assignee:
Merck Sharp & Dohme Corp.
Inventors:
Gregory L. Adams, Jason M. Cox, John S. Debenham, Scott Edmondson, Eric J. Gilbert, Yan Guo, Yu Jiang, Hubert Josien, Hyunjin M. Kim, Ping Lan, Shouwu Miao, Christopher W. Plummer, Murali Rajagopalan, Unmesh Shah, Zhongxiang Sun, Quang T. Truong, Feroze Ujjainwalla, Francisco Velazquez, Srikanth Venkatraman, Takao Suzuki, Nengxue Wang
Abstract: A web detection system processes webpage information and performs automated feature extraction of webpages including machine processable information. In an embodiment, the web detection system determines a subset of webpages having a target characteristic by processing markup language. For a webpage of the subset, the web detection system determines that a first image overlaps at least a portion of a second image in the webpage. The web detection system generates an image of the webpage such that the portion of the second image is obscured by the first image. The web detection system determines a graphical feature of the webpage by processing the image, e.g., using optical character recognition. Responsive to determining that the graphical feature corresponds to graphical features of images of a different set of webpages associated with a target entity, the web detection system determines that the webpage is also associated with the target entity.
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 is directed to a pharmaceutical composition comprising the compound suvorexant, or a pharmaceutically acceptable salt thereof, a concentration-enhancing polymer, and optionally a pharmaceutically acceptable surfactant.
Abstract: HSV glycoprotein B-VSV-G1 fusion proteins and variants thereof, HSV glycoprotein C antigenic peptide constructs and variants thereof, HSV immunogenic compositions and protein vaccines including the peptide constructs, and HSV DNA vaccines encoding the amino acid sequence of the peptide constructs, as well as methods of using the vaccines and compositions comprising the vaccines.
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:
Grant
Filed:
October 8, 2018
Date of Patent:
November 2, 2021
Assignee:
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: Disclosed herein are compounds of formula (I) which are inhibitors of an IDO enzyme: 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 16, 2019
Publication date:
October 28, 2021
Applicant:
Merck Sharp & Dohme Corp.
Inventors:
Dane Clausen, Xavier Fradera, Liangqin Guo, Yongxin Han, Shuwen He, Xianhai Huang, Joseph Kozlowski, Guoqing Li, Jongwon Lim, Theodore A. Martinot, Alexander Pasternak, Nunzio Sciammetta, Andreas Verras, Li Xiao, Wensheng Yu, Rui Zhang
Abstract: The present invention provides immunogenic compositions having one or more polysaccharide-protein conjugates in which one or more polysaccharides from Streptococcus pneumoniae bacterial capsules are conjugated to a carrier protein in an aprotic solvent such as dimethylsulfoxide (DMSO). The present invention also provides methods for providing an enhanced immune response to a pneumococcal polysaccharide protein conjugate vaccine comprising administering to a human subject an immunogenic composition comprising polysaccharide-protein conjugates prepared in DMSO conditions.
Type:
Application
Filed:
July 7, 2021
Publication date:
October 28, 2021
Applicant:
Merck Sharp & Dohme Corp.
Inventors:
Jian He, John E. MacNair, William J. Smith, Michael A. Winters, Joseph G. Joyce, Chitrananda Abeygunawardana, Luwy Musey, Hari Pujar, Julie M. Skinner, Patrick McHugh
Abstract: The present invention provides immunogenic compositions having one or more polysaccharide-protein conjugates in which one or more polysaccharides from Streptococcus pneumoniae bacterial capsules are conjugated to a carrier protein in an aprotic solvent such as dimethylsulfoxide (DMSO). The present invention also provides methods for providing an enhanced immune response to a pneumococcal polysaccharide protein conjugate vaccine comprising administering to a human subject an immunogenic composition comprising polysaccharide-protein conjugates prepared in DMSO conditions.
Type:
Application
Filed:
July 7, 2021
Publication date:
October 28, 2021
Applicant:
Merck Sharp & Dohme Corp.
Inventors:
Jian He, John E. MacNair, William J. Smith, Michael A. Winters, Joseph G. Joyce, Chitrananda Abeygunawardana, Luwy Musey, Hari Pujar
Abstract: The present invention provides molecules, such as ISVDs and Nanobodies, that bind to PD1 and LAG3 and, optionally to 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:
May 17, 2019
Date of Patent:
October 26, 2021
Assignee:
Merck Sharp & Dohme Corp.
Inventors:
Edward Bowman, Maribel Beaumont, Marie-Ange Buyse, Carlo Boutton, Bruno Dombrecht, Robert A. Kastelein, David Vlerick
Abstract: The present invention relates to stable formulations comprising antibodies or antigen-binding fragments thereof that bind to respiratory syncytial virus (RSV). Also provided are methods of preventing and/or treating RSV-related diseases with the formulations of the invention.
Type:
Application
Filed:
October 14, 2019
Publication date:
October 21, 2021
Applicant:
Merck Sharp & Dohme Corp.
Inventors:
Venus Hashemi, Arnab De, Chakravarthy Nachu Narasimhan
Abstract: The present invention is directed to pyrazol-4-yl-pyridine compounds which are allosteric modulators of the M4 muscarinic acetylcholine receptor. 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 M4 muscarinic acetylcholine 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 M4 muscarinic acetylcholine receptors are involved.
Inventors:
John J. Acton, III, Jianming Bao, Qiaolin Deng, Melissa Egbertson, Ronald Ferguson, II, Xiaolei Gao, Scott Timothy Harrison, Sandra L. Knowles, Chunsing Li, Michael Man-Chu Lo, Robert D. Mazzola, Jr., Zhaoyang Meng, Meng Na, Michael T. Rudd, Oleg Selyutin, David M. Tellers, Ling Tong, Fengqi Zhang
Abstract: The present disclosure describes combination therapies comprising an antagonist of Programmed Death 1 receptor (PD-1) and a multi-RTK inhibitor, and the use of the combination therapies for the treatment of cancer. The multi-RTK inhibitor may be represented by Formula (I): wherein R1 is C1-6 alkyl or C3-8 cycloalkyl, R2 is a hydrogen atom or C1-6 alkoxy, and R3 is a hydrogen atom or a halogen atom. A tumor therapeutic agent is disclosed that combines a compound or pharmaceutically acceptable salt thereof represented by Formula I and an anti-PD-1 antibody.
Abstract: Disclosed herein is a compound of formula (I), or a pharmaceutically acceptable salt thereof. Also disclosed herein are uses of a compound 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 a composition in the potential treatment or prevention of an 1DO-associated disease or disorder.