Abstract: The disclosure provides a method for treating a subject afflicted with a tumor comprising administering to the subject a therapeutically effective amount of an anti-PD-1 antibody or antigen-binding portion thereof or an anti-PD-L1 antibody or anti-gen-binding portion thereof, wherein the subject is identified as having a high inflammatory gene signature score and a tumor that has a high tumor mutation burden (TMB) status. In some embodiments, the high inflammatory gene signature score is determined by measuring the expression of a panel of inflammatory genes in a tumor sample obtained from the subject, wherein the inflammatory gene panel comprises CD274 (PD-L1), CD8A, LAG3, and STAT1.
Type:
Application
Filed:
March 27, 2020
Publication date:
June 23, 2022
Applicant:
Bristol-Myers Squibb Company
Inventors:
Ming LEI, Nathan O. SIEMERS, Dimple PANDYA, Han CHANG, Teresa K. SANCHEZ, Christopher T. HARBISON, Peter M. SZABO, Zachary S. BOYD, Xiaozhong QIAN, Samy Abdel SACI, Tina C. YOUNG, Sujaya SRINIVASAN, Megan M. WIND-ROTOLO, Jasmine RIZZO, Donald G. JACKSON, Alice M. WALSH
Abstract: The present disclosure generally relates to modified relaxin polypeptides, such as modified human relaxin 2 polypeptides, comprising a non-naturally encoded amino acid which is linked to a pharmacokinetic enhancer, and therapeutic uses of such polypeptides, such as for the treatment of cardiovascular conditions (such as heart failure) and/or conditions relating to fibrosis.
Type:
Grant
Filed:
March 11, 2021
Date of Patent:
June 21, 2022
Assignee:
BRISTOL-MYERS SQUIBB COMPANY
Inventors:
Gene M. Dubowchik, Olafur S. Gudmundsson, Xiaojun Han, R. Michael Lawrence, Dasa Lipovsek, Cort S. Madsen, Claudio Mapelli, Paul E. Morin, Michael C. Myers
Abstract: The present invention relates to antagonizing the activity of IL-17A, IL-17F and IL-23 using bispecific antibodies that comprise a binding entity that is cross-reactive for IL-17A and IL-17F and a binding entity that binds IL-23p19. The present invention relates to novel bispecific antibody formats and methods of using the same.
Type:
Application
Filed:
January 7, 2022
Publication date:
June 16, 2022
Applicant:
Bristol-Myers Squibb Company
Inventors:
Brenda L. Stevens, Mark W. Rixon, Scott R. Presnell
Abstract: The present disclosure relates to antisense oligonucleotides, which target SNCA mRNA (e.g., at an intron exon junction) in a cell, leading to reduced expression of SNCA protein. Reduction of SNCA protein expression is beneficial for the treatment of certain medical disorders, e.g., a neurological disorder.
Type:
Grant
Filed:
February 2, 2021
Date of Patent:
June 14, 2022
Assignee:
Bristol-Myers Squibb Company
Inventors:
Richard E. Olson, Angela M. Cacace, Jere E. Meredith, Jr., Nino Devidze, James K. Loy, Carl J. Baldick, Annapurna Pendri, Ivar M. McDonald, Peter Hagedorn, Marianne Lerbech Jensen
Abstract: In certain embodiments, the present invention provides novel antibody purification methods and systems using a potentially simple and cost-efficient means. In some embodiments, customized Z-33 derived from Staphylococcus aureus Protein A is used to construct immuno-amphiphile molecules which can assemble into immunofibers in aqueous solution with bioactive epitopes on the surface and have IgG binding ability.
Type:
Grant
Filed:
March 28, 2018
Date of Patent:
June 14, 2022
Assignees:
THE JOHNS HOPKINS UNIVERSITY, BRISTOL-MYERS SQUIBB COMPANY
Inventors:
Honggang Cui, Yi Li, Xuankuo Xu, Lye Lin Lock, Zhengjian Li
Abstract: Disclosed herein are fusion proteins comprising: (a) a first polypeptide comprising Interleukin-2 (IL2); and (b) a second polypeptide, fused in frame to the first polypeptide, wherein the second polypeptide comprises an extracellular domain of Interleukin-2 Receptor alpha (IL2R?), wherein IL2 or IL2R? comprises at least one fewer glycosylation site compared to native IL2 or native IL2R?. Methods of production and methods of therapeutic use of the fusion proteins are also disclosed.
Type:
Grant
Filed:
March 27, 2019
Date of Patent:
June 14, 2022
Assignee:
Bristol-Myers Squibb Company
Inventors:
Mary Struthers, Jonathan Harry Davis, Michael Louis Doyle, Priyanka Apurva Madia
Abstract: The present disclosure provides compounds which are immunomodulators and thus are useful for the amelioration of various diseases, including cancer and infectious diseases.
Type:
Grant
Filed:
December 11, 2019
Date of Patent:
June 14, 2022
Assignee:
Bristol-Myers Squibb Company
Inventors:
Kevin W. Gillman, Jason Goodrich, Kenneth M. Boy, Yunhui Zhang, Claudio Mapelli, Michael A. Poss, Paul Michael Scola, David R. Langley, Nicholas A. Meanwell
Abstract: The disclosure provides for antibodies that bind CD40, including a humanized antibody and a chimeric antibody with different Fc domains. The antibodies bind CD40 and do not exhibit CD40 agonist activity. The antibodies may comprise a modified IgG1 Fc domain, and exhibit minimal activation of immature dendritic cells. Compositions comprising antibodies, methods of use for treatment of diseases involving CD40 activity, and use in the preparation of a medicament for treatment of a disease involving CD40 activity are provided.
Type:
Application
Filed:
December 23, 2021
Publication date:
June 9, 2022
Applicant:
Bristol-Myers Squibb Company
Inventors:
Aaron YAMNIUK, Mary STRUTHERS, Suzanne J. SUCHARD
Abstract: Provided herein are system, apparatus, device, method, and/or computer program product embodiments, and/or combinations and sub-combinations thereof, for classifying a document using CNN and BiLSTM.
Abstract: There are disclosed compounds that modulate or inhibit the enzymatic activity of indoleamine 2,3-dioxygenase (IDO), pharmaceutical compositions containing said compound and methods of treating proliferative disorders, such as cancer, viral infections and/or inflammatory disorders utilizing the compounds of the invention.
Type:
Grant
Filed:
August 25, 2017
Date of Patent:
June 7, 2022
Assignee:
Bristol-Myers Squibb Company
Inventors:
Liping Zhang, Emily Charlotte Cherney, James Aaron Balog, Xiao Zhu
Abstract: The present invention provides isolated monoclonal antibodies, particularly human antibodies, that bind to human Cluster of Differentiation 73 (CD73) with high affinity, and inhibit the activity of CD73, and optionally mediate antibody dependent CD73 internalization. Nucleic acid molecules encoding the antibodies of the invention, expression vectors, host cells and methods for expressing the antibodies of the invention are also provided. Immunoconjugates, bispecific molecules and pharmaceutical compositions comprising the antibodies of the invention are also provided. The invention also provides methods for inhibiting the growth of a tumor cell expressing CD73 using the antibodies of the invention, including methods for treating various cancers.
Type:
Grant
Filed:
August 30, 2018
Date of Patent:
June 7, 2022
Assignee:
BRISTOL-MYERS SQUIBB COMPANY
Inventors:
Nils Lonberg, Alan J. Korman, Bryan C. Barnhart, Aaron P. Yamniuk, Mohan Srinivasan, Karla A. Henning, Ming Lei, Emanuela Sega, Angela Goodenough, Maria N. Jure-Kunkel, Guodong Chen, John S. Sack, Richard Y. Huang, Martin J. Corbett, Joseph E. Myers, Jr., Liang Schweizer, Sandra V. Hatcher, Haichun Huang, Pingping Zhang
Abstract: The disclosure is directed to methods of treating cancer in subjects with a combination of a monoclonal antibody and (R)-N-(4-chlorophenyl)-2-(cis-4-(6-fluoroquinolin-4-yl)cyclohexyl)propanamide, or a salt thereof.
Type:
Grant
Filed:
September 28, 2018
Date of Patent:
June 7, 2022
Assignee:
Bristol-Myers Squibb Company
Inventors:
Paul Andrew Basciano, Justine Kamilah Walker, Penny E. Phillips, Li Zhu, Steven H. Bernstein, James Cassidy, Katy Lynn Simonsen, Alexander Azrilevich, Shivani Srivastava
Abstract: Disclosed are imidazole and thiazole compounds, as well as pharmaceutical compositions and methods of use thereof. One embodiment is a compound having the structure and pharmaceutically acceptable salts, prodrugs and N-oxides thereof (and solvates and hydrates thereof), wherein X, A, Z, R1 and R? are as described herein. In certain embodiments, a compound disclosed herein inhibits TGF-?, and can be used to treat disease by blocking TGF-? signaling.
Type:
Grant
Filed:
March 21, 2019
Date of Patent:
June 7, 2022
Assignees:
Rigel Pharmaceuticals, hic., Bristol-Myers Squibb Company
Inventors:
Todd Kinsella, Marina Gelman, Hui Hong, Ihab S. Darwish, Rajinder Singh, Jiaxin Yu, Robert M. Borzilleri, Upender Velaparthi, Peiying Liu, Chetan Padmakar Dame, Hasibur Rahaman, Jayakumar Sankara Warrier
Abstract: The present invention provides compounds of Formula (I) or a stereoisomer, tautomer, or pharmaceutically acceptable salt or solvate thereof, wherein all the variables are as defined herein. These compounds are selective LPA receptor inhibitors.
Type:
Grant
Filed:
December 18, 2018
Date of Patent:
June 7, 2022
Assignee:
Bristol-Myers Squibb Company
Inventors:
Yan Shi, Peter Tai Wah Cheng, Hao Zhang, Jun Li, Tianan Fang, James R. Corte
Abstract: The disclosure provides for antibodies that bind CD40, including a humanized antibody. The antibodies bind CD40 and do not exhibit CD40 agonist activity. The antibodies may comprise a modified IgG1 Fc domain, and exhibit minimal activation of immature dendritic cells. Compositions comprising antibodies, methods of use for treatment of diseases involving CD40 activity, and use in the preparation of a medicament for treatment of a disease involving CD40 activity are provided.
Type:
Application
Filed:
February 11, 2022
Publication date:
June 2, 2022
Applicant:
Bristol-Myers Squibb Company
Inventors:
Aaron YAMNIUK, Mary STRUTHERS, Stanley R. KRYSTEK, Jr., Akbar NAYEEM, Ginger RAKESTRAW
Abstract: Provided herein are novel 10Fn3 domains which specifically bind to PD-L1, as well as imaging agents based on the same for diagnostics.
Type:
Grant
Filed:
May 31, 2017
Date of Patent:
May 31, 2022
Assignee:
BRISTOL-MYERS SQUIBB COMPANY
Inventors:
Paul E. Morin, David Donnelly, Dasa Lipovsek, Jochem Gokemeijer, Maria Jure-Kunkel, David Fabrizio, Martin C. Wright, Douglas Dischino, Samuel J. Bonacorsi, Jr., Ralph Adam Smith, Virginie Lafont, Daniel Cohen, David K. Leung
Abstract: The present invention provides isolated monoclonal antibodies that specifically bind LAG-3, and have optimized functional properties compared to previously described anti-LAG-3 antibodies, such as antibody 25F7 (US 2011/0150892 A1). These properties include reduced deamidation sites, while still retaining high affinity binding to human LAG-3, and physical (i.e., thermal and chemical) stability. Nucleic acid molecules encoding the antibodies of the invention, expression vectors, host cells and methods for expressing the antibodies of the invention are also provided, as well as immunoconjugates, bispecific molecules and pharmaceutical compositions comprising the antibodies. The present invention also provides methods for detecting LAG-3, as well as methods for treating stimulating immune responses using an anti-LAG-3 antibody of the invention. Combination therapy, in which the antibodies are co-administered with at least one additional immunostimulatory antibody, is also provided.
Abstract: Provided herein are methods for refolding denatured protein (e.g., from inclusion bodies) that do not require the use of a denaturing agent. Exemplary methods use a high pH for solubilizing denatured protein, followed by a decrease in pH for refolding the proteins.
Abstract: There are disclosed compounds that modulate or inhibit the enzymatic activity of indoleamine 2,3-dioxygenase (IDO), pharmaceutical compositions containing said compounds and methods of treating proliferative disorders, such as cancer, viral infections and/or inflammatory disorders utilizing the compounds of the invention.
Type:
Grant
Filed:
August 25, 2017
Date of Patent:
May 24, 2022
Assignee:
Bristol-Myers Squibb Company
Inventors:
Emily Charlotte Cherney, Weifang Shan, Liping Zhang, Susheel Jethanand Nara, Audris Huang, James Aaron Balog
Abstract: The present invention is directed to compounds of the formulae I, II and III as shown below wherein all substituents are defined herein, as well as pharmaceutically acceptable compositions comprising compounds of the invention and methods of using said compositions in the treatment of various disorders.
Type:
Grant
Filed:
November 14, 2019
Date of Patent:
May 24, 2022
Assignee:
Bristol-Myers Squibb Company
Inventors:
Brian E. Fink, Dharmpal S. Dodd, Steven J. Walker, Libing Chen, Yufen Zhao, Zheming Ruan, Lan-Ying Qin, Peter Kinam Park, Muthoni G. Kamau, Lalgudi S. Harikrishnan