Abstract: The present disclosure relates to methods of treating a cellular proliferative disorder (e.g., cancer) comprising administering: (a) an anti-human PD-1 antibody or antigen binding fragment thereof; and (b) an Immunoconjugate of Formula (I): wherein: Ab is an antibody that binds to Trop-2; and n is an integer from 1 to 10. Also disclosed are therapeutic combinations and kits containing such agents for the treatment of cancers.
Abstract: An ampoule includes a body having a cavity for storing a medicament, a neck coupled to the body and defining a nozzle in communication with the cavity of the body, a removable cap coupled to the nozzle, and an anti-choking miter coupled to the removable cap, the anti-chocking miter being wider than the removable cap.
Type:
Application
Filed:
November 11, 2022
Publication date:
January 2, 2025
Applicant:
Merck Sharp & Dohme LLC
Inventors:
Ramprasad B. Halthore, Atul Karande, Derrick M. Smith
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:
Grant
Filed:
October 25, 2022
Date of Patent:
December 31, 2024
Assignee:
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: An insulin conjugate comprising or consisting of a tetra-valent sugar cluster is described. The tetra-valent sugar cluster is provided by tetra-dentate linker having four arms, wherein each arm of the tetra-dentate linker is independently covalently linked to a ligand comprising or consisting of a saccharide, such as a monosaccharide, disaccharide, trisaccharide, tetrasaccharide, or branched trisaccharide. In particular aspects, the insulin conjugate displays a pharmacokinetic (PK) and/or pharmacodynamic (PD) profile that is responsive to the systemic concentrations of a saccharide such as glucose or alpha-methylmannose.
Type:
Application
Filed:
November 16, 2022
Publication date:
December 26, 2024
Applicant:
Merck Sharp & Dohme LLC
Inventors:
Pei Huo, Songnian Lin, Christopher R. Moyes, Dmitri A. Pissarnitski, Zhiqiang Zhao, David N. Hunter, Yuping Zhu
Abstract: The invention provides compositions of anti-PD-1 antibodies or antigen-binding fragments thereof with less than or equal to about 3.0% oxidation of Met105 in the CDRH3 heavy chain region, and methods of obtaining the purified compositions. The invention also provides compositions comprising anti-PD-1 antibody main species and acidic species thereof, wherein the amount of acidic species is about 1.0-12.0%.
Type:
Application
Filed:
September 6, 2024
Publication date:
December 26, 2024
Applicant:
Merck Sharp & Dohme LLC
Inventors:
Mark A. Brower, Chung-Jr Huang, Brian Wai Kwan, William Nicholas Napoli, Bhumit A. Patel, Nuno J. Dos Santos Pinto, Douglas Dennis Richardson, II, Sen Xu
Abstract: In some examples, a vial-to-syringe converter includes a plunger rod, an adapter including a body having a piercing spike, a receiver and a lumen extending between the spike and the receiver, the body further including at least one laterally-extending flange, and a needle in communication with the receiver and configured to deliver a medicament to a patient's body.
Type:
Application
Filed:
November 1, 2022
Publication date:
December 26, 2024
Applicant:
Merck Sharp & Dohme LLC
Inventors:
Daniel A. Bonanno, Eduardo Cristofolli, Cassie Megna, Wail A. Rasheed, Ophelia L. Wells
Abstract: Described herein are compounds of Formula I; and pharmaceutically acceptable salts thereof, wherein A, X, R1, R2, m, n, and p are as defined herein. The compounds of Formula I, and pharmaceutically acceptable salts thereof, 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 24, 2022
Publication date:
December 26, 2024
Applicant:
Merck Sharp & Dohme LLC
Inventors:
Abdelghani Abe Achab, Jenny Lorena Rico Duque, Xavier Fradera, Joey L. Methot, Phieng Siliphaivanh, Brandon A. Vara, Hongjun Zhang
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: 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: 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: 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: 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