Abstract: A method or system for training a convolutional neural network (CNN) for medical imaging analysis. The system pre-trains the CNN's encoder using a dataset of unlabeled 3D medical images. Each 3D image includes an annotated slice delineating a boundary of a lesion and multiple non-annotated 2D slices above and below the annotated slice. The system then fine-tunes the pre-trained encoder using an annotated 2D image dataset. The annotated 2D image dataset includes multiple 2D slices of lesions, each including an annotation that delineates a boundary of a corresponding lesion.
Abstract: The present invention provides a compound of Formula (I) and the pharmaceutically acceptable salts, esters, and prodrugs thereof, which are PRMT5 inhibitors. Also provided are methods of making compounds of Formula I, pharmaceutical compositions comprising compounds of Formula I, and methods of using these compounds to treat cancer, sickle cell, and hereditary persistence of foetal hemoglobin (HPFH) mutations.
Type:
Grant
Filed:
August 5, 2019
Date of Patent:
December 24, 2024
Assignees:
Merck Sharp & Dohme LLC, MSD International GmbH
Inventors:
Michelle Machacek, David Witter, Craig Gibeau, Chunhui Huang, Shuhei Kawamura, David L. Sloman, Phieng Siliphaivanh, Ryan Quiroz, Murray Wan, Sebastian Schneider, Charles S. Yeung, Michael H. Reutershan, Timothy J. Henderson, Jean-Laurent Paparin, Houcine Rahali, Jonathan M. E. Hughes, Sulagna Sanyal, Yingchun Ye, David A. Candito, Patrick S. Fier, Steven M. Silverman
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:
April 8, 2022
Date of Patent:
December 24, 2024
Assignee:
Merck Sharp & Dohme LLC
Inventors:
Daria Hazuda, Michael D. Miller, Jay A. Grobler, Deborah Anne Nicoll-Griffith
Abstract: In some examples, an injector includes a base, a housing movable relative to the base, a needle unit disposed within the base, the needle unit comprising at least one piercing needle configured to pierce a pierceable membrane of a drug product container, and at least one microneedle disposed on an opposite side of the at least one piercing needle, and a driving mechanism configured and arranged to drive at least one of the drug product container and the needle unit toward another of the drug product container and the needle unit.
Type:
Application
Filed:
November 1, 2022
Publication date:
December 19, 2024
Applicant:
Merck Sharp & Dohme LLC
Inventors:
Daniel A. Bonanno, John B. Cline, Eduardo Cristofolli, Cassie Megna, Wail A. Rasheed, Ophelia L. Wells
Abstract: The present disclosure provides methods for the acute treatment of migraine with or without aura, comprising the administration of ubrogepant. In particular, the present disclosure provides methods for the acute treatment of migraine in patients having hepatic impairment; in patients with renal impairment; and in patients concurrently taking CYP3A4 modulators or BCRP and/or P-gp only inhibitors.
Type:
Grant
Filed:
May 13, 2024
Date of Patent:
December 17, 2024
Assignee:
Merck Sharp & Dohme LLC
Inventors:
Mary Ann Johnson, Leonardo Resende Allain, W. Mark Eickhoff, Craig B. Ikeda, Chad D. Brown, Francis J. Flanagan, Jr., Rebecca Nofsinger, Melanie J. Marota, Lisa Lupton, Paresh B. Patel, Hanmi Xi, Wei Xu
Abstract: The present disclosure provides, among other things, a vaccine composition that includes a squalene nanoemulsion (SNE) adjuvant and 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:
June 6, 2024
Publication date:
December 12, 2024
Applicant:
Merck Sharp & Dohme LLC
Inventors:
Patrick L. Ahl, William J. Smith, Randal J. Soukup, Nicole Lea Sullivan, John Gaspar, Julie M. Skinner
Abstract: The present disclosure is directed to benzoxazinone derivatives of Formula I and their use for selectively killing HIV infected GAG-POL expressing cells without concomitant cytotoxicity to HIV naive 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:
Application
Filed:
October 10, 2022
Publication date:
December 12, 2024
Applicant:
Merck Sharp & Dohme LLC
Inventors:
Abdellatif El Marrouni, Antonella Converso, Ashley Forster
Abstract: The present invention provides a number of process improvements related to the conjugation of capsular polysaccharides from Streptococcus pneumoniae to a carrier protein. These process are serotype specific and include acid hydrolysis, addition of sodium chloride to the reductive amination reaction, and addition of sucrose to dissolve polysaccharides. Polysaccharide-protein conjugates prepared using the processes of the invention can be included in multivalent pneumococcal conjugate vaccines.
Type:
Grant
Filed:
June 9, 2022
Date of Patent:
December 10, 2024
Assignee:
Merck Sharp & Dohme LLC
Inventors:
Patrick McHugh, Michael Albert Winters, Janelle Konietzko
Abstract: The present invention relates to purified antibody and antigen-binding fragment compositions that lack sulfated tyrosine on one or more tyrosine residues in the immunoglobulin chains. Purification methods for removing sulfated tyrosine variants from antibody and antigen-binding fragment compositions are also provided.
Abstract: The invention is related to the preparation of protected piperidine carboxylates suitable for use as intermediates that lead, via a series of additional process steps, including a sulfation of a hydroxy urea compound, to the preparation of the beta lactamase inhibitor (2S,5R)-7-oxo-N-piperidin-4-yl-6-(sulfoxy)-1,6-diazabicyclo[3.2.1]octane-2-carboxamide.
Inventors:
John Y. L. Chung, Tetsuji Itoh, Jungchul Kim, Jacob Henry Waldman, Debra J. Wallace, Andrew Wood, Feng Xu, Andrew Gibson, Jeremy Peter Scott
Abstract: The present invention is directed to certain 2-aminoquinzaoline derivatives of Formula (I): Formula (I) and pharmaceutically acceptable salts thereof, wherein 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:
Application
Filed:
September 26, 2022
Publication date:
December 5, 2024
Applicant:
Merck Sharp & Dohme LLC
Inventors:
Peter H. Fuller, Anmol Gulati, Solomon D. Kattar, Mitchell H. Keylor, Kaila A. Margrey, Luis Torres, Xin Yan
Abstract: Compounds of formula I, that modulate DCAF15 and induce RBM139 protein degradation, pharmaceutical compositions containing these compounds, and methods of using these compounds for treating diseases associated with RBM39 protein activity and DCAF15 modulation are described herein.
Type:
Application
Filed:
October 7, 2022
Publication date:
December 5, 2024
Applicant:
Merck Sharp & Dohme LLC
Inventors:
John P. Caldwell, Ping Lan, Hongwu Wang, Paul Wehn
Abstract: Novel compounds of the structural formula (I), and pharmaceutically acceptable salts, hydrates and solvates thereof, are inhibitors of NLRP3 and may be useful in the treatment, prevention, management, amelioration, control and suppression of diseases mediated by NLPR3. The compounds of structural formula I may be useful in the treatment, prevention or management of diseases, disorders and conditions mediated by NLRP3 such as, but not limited to, gout, pseudogout, CAPS, NASH fibrosis, heart failure, idiopathic pericarditis, atopic dermatitis, inflammatory bowel disease, Alzheimer's Disease, Parkinson's Disease and traumatic brain injury.
Type:
Application
Filed:
May 30, 2024
Publication date:
December 5, 2024
Applicant:
Merck Sharp & Dohme LLC
Inventors:
Zachary G. Brill, Chen Cheng, Donna A.A.W. Hayes, Kyle S. McClymont, Rohan Rajiv Merchant, Maoqun Tian
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. 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 diseases caused by S. pneumoniae. The compositions of the invention are also useful as part of treatment regimes that provide complementary protection for patients that have been vaccinated with a multivalent vaccine indicated for the prevention of pneumococcal disease.
Type:
Application
Filed:
August 22, 2024
Publication date:
December 5, 2024
Applicant:
Merck Sharp & Dohme LLC
Inventors:
William J. Smith, Patrick McHugh, Michael Albert Winters, Julie M. Skinner, Jian He, Luwy Musey, Chitrananda Abeygunawardana, Yadong Adam Cui, Michael J. Kosinski
Abstract: The present invention provides methods of treatment for recurrent cancer(s) through combination therapy with an agent that inhibits programmed death-1 protein (PD-1) signaling and an agent that inhibits poly [ADP-ribose] polymerase (PARP) signaling.
Type:
Grant
Filed:
May 9, 2018
Date of Patent:
December 3, 2024
Assignees:
TESARO, Inc., MERCK SHARP & DOHME B.V.
Inventors:
Dmitri Bobilev, Bruce Dezube, Peng Sun, Andrew R. Ferguson
Abstract: Disclosed herein is a compound of formula (I), or a pharmaceutically acceptable salt thereof: Also disclosed herein are uses of the compounds 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 the compositions in the potential treatment or prevention of an IDO-associated disease or disorder.
Abstract: The invention relates to novel compounds and formulations. Further, the invention relates to novel compounds and formulations useful in pneumococcal and pneumococcal conjugate vaccines. More specifically, the invention relates to compositions comprising pneumococcal conjugates and one or more compounds of Formula I, Ia, II, IIa, III, IIIa, IV, or IVa, or a pharmaceutically acceptable salt thereof, prepared as stable nanoemulsions (herein referred to as “SNE adjuvant compositions” or “SNEs”).
Type:
Application
Filed:
May 16, 2024
Publication date:
November 28, 2024
Applicant:
Merck Sharp & Dohme LLC
Inventors:
Patrick L. Ahl, Peter J. Manley, Izzat T. Raheem, W. Michael Seganish, William J. Smith
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:
Grant
Filed:
October 11, 2019
Date of Patent:
November 26, 2024
Assignee:
Merck Sharp & Dohme LLC
Inventors:
Dane Clausen, Ping Chen, Xavier Fradera, Liangqin Guo, Yongxin Han, Shuwen He, Jongwon Lim, Theodore A. Martinot, Alexander Pasternak, Li Xiao, Wensheng Yu
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. 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. The compositions of the invention are also useful as part of treatment regimes that provide complementary protection for patients that have been vaccinated with a multivalent vaccine indicated for the prevention of pneumococcal disease.
Type:
Application
Filed:
August 2, 2024
Publication date:
November 21, 2024
Applicant:
Merck Sharp & Dohme LLC
Inventors:
Chitrananda Abeygunawardana, Yadong Adam Cui, Romulo Ferrero, Jian He, Luwy Musey, Tanaz Petigara, Julie M. Skinner
Abstract: A method is described for producing a pneumococcal capsular polysaccharide protein conjugate in which one or more activated pneumococcal polysaccharides of particular pneumococcal serotypes and carrier protein are separately lyophilized in the form of lyospheres of carrier protein and lyospheres of the one or more polysaccharides. A predetermined amount of carrier protein lyospheres and activated polysaccharide lyospheres are mixed together and the mixture reconstituted in an organic solvent to produce polysaccharide carrier protein conjugates. A plurality of conjugates, each comprising polysaccharides of a particular serotype, may be used to produce multivalent pneumococcal immunogenic compositions having a combination of conjugates for use in vaccines.
Type:
Grant
Filed:
April 25, 2019
Date of Patent:
November 19, 2024
Assignee:
Merck Sharp & Dohme LLC
Inventors:
Patrick Leonard Ahl, Akhilesh Bhambhani, Christopher Jon Farrell, Patrick McHugh, Morrisa C. Jones, Daniel D. Roth, Jessica R. Sinacola, Justin Stanbro, Matthew P. Watson, Emily Wen, Michael A. Winters