Abstract: Disclosed are antibodies that bind specifically to the receptor TNF superfamily member 15 (TNFSF15), also known as TL1A. Methods of making and using the anti-TL1A antibodies are also described.
Abstract: The disclosure provides a method for treating a subject afflicted with a tumor derived from a small cell lung cancer (SCLC) having a high tumor mutational burden (TMB) status comprising administering to the subject a monotherapy comprising an anti-PD-1 antibody or a combination therapy comprising an anti-PD-1 antibody and an anti-CTLA-4 antibody. The present disclosure also provides a method for identifying a subject suitable for treatment with an anti-PD-1 antibody or a combination therapy comprising an anti-PD-1 antibody and an anti-CTLA-4 antibody comprising measuring a TMB status of a biological sample of the subject. A high TMB status identifies the patient as suitable for treatment with an anti-PD-1 antibody or antigen-binding portion thereof. The TMB status can be determined by sequencing nucleic acids in the tumor and identifying a genomic alteration, e.g., a somatic nonsynonymous mutation, in the sequenced nucleic acids.
Type:
Application
Filed:
October 17, 2022
Publication date:
September 21, 2023
Applicant:
Bristol-Myers Squibb Company
Inventors:
Prabhu Seshaiyer BHAGAVATHEESWARAN, Nicholas Allan John BOTWOOD, Han CHANG, William J. GEESE, Sabine MAIER, Giovanni SELVAGGI, Joseph Daniel SZUSTAKOWSKI
Abstract: The disclosure provides a method for treating a subject afflicted with a tumor, e.g., lung cancer, having a high tumor mutation burden (TMB) status comprising administering to the subject an immunotherapy, e.g., an anti-PD-1 antibody or antigen-binding portion thereof. The present disclosure also provides a method for identifying a subject suitable for an immunotherapy, e.g., a treatment with an anti-PD-1 antibody or antigen-binding portion thereof, comprising measuring a TMB status of a biological sample of the subject. A high TMB status identifies the patient as suitable for treatment with an anti-PD-1 antibody or antigen-binding portion thereof. The TMB status can be determined by sequencing nucleic acids in the tumor and identifying a genomic alteration, e.g., a somatic nonsynonymous mutation, in the sequenced nucleic acids.
Type:
Application
Filed:
December 7, 2022
Publication date:
September 21, 2023
Applicant:
Bristol-Myers Squibb Company
Inventors:
Prabhu Seshaiyer BHAGAVATHEESWARAN, Nicholas Allan John BOTWOOD, Han CHANG, Yali FU, William J. GEESE, George A. GREEN, Diane HEALEY, Sabine MAIER, Faith E. NATHAN, Abderrahim OUKESSOU, Giovanni SELVAGGI, Joseph Daniel SZUSTAKOWSKI
Abstract: The present disclosure discloses methods for purifying antibodies providing an air overlay or headspace to single-use storage bags containing the antibody during purification. In specific embodiments, the application relates to purification of antibodies to human TIGIT (T cell immunoreceptor with Ig and ITIM domains), such as antibody 22G2, which decrease unwanted disulfide bond reduction. The application further provides depth filtration at lower throughput and/or flux, which also minimizes unwanted disulfide bond reduction.
Type:
Grant
Filed:
April 24, 2018
Date of Patent:
September 19, 2023
Assignee:
BRISTOL-MYERS SQUIBB COMPANY
Inventors:
John C. Fann, Brian W. O'Mara, Laura R. Smith
Abstract: The present disclosure provides methods of using a calcium oscillation assay and/or a sequence score calculation to identify a molecule that is safe for administration. The disclosure also includes a method of selecting or identifying a molecule having tolerable in vivo neurotoxicity using a calcium oscillation assay, a sequence score method, an in vivo tolerability assay, or any combination thereof.
Type:
Grant
Filed:
February 4, 2016
Date of Patent:
September 19, 2023
Assignee:
BRISTOL-MYERS SQUIBB COMPANY
Inventors:
Richard E. Olson, Angela M. Cacace, Peter Hagedorn, Anja Mølhart Høg, Niels Fisker Nielsen, Dong LI, Jeffrey M. Brown, Stephen E. Mercer, Marianne Lerbech Jensen
Abstract: This disclosure provides a method for treating a subject afflicted with tumor, which method comprises administering to the subject an antibody or an antigen-binding portion thereof that specifically binds to a Programmed Death-1 (PD-1) receptor and inhibits PD-1 activity. In some embodiments, the tumor is derived from a non-small cell lung cancer (NSCLC). In some embodiments, the tumor expresses Programmed Death Ligand 1. In some embodiments, the subject carries a wild-type STK11 gene.
Type:
Application
Filed:
January 30, 2023
Publication date:
September 7, 2023
Applicant:
Bristol-Myers Squibb Company
Inventors:
Robin EDWARDS, William J. GEESE, Danielle M. GREENAWALT
Abstract: The present invention provide novel immunofiber compositions for protein or peptide purification and simple and cost-efficient methods and systems using these compositions. In some embodiments, the immunofibers comprise a customized Z-33 peptide derived from Staphylococcus aureus Protein A which is used to construct immuno-amphiphile molecules that assemble into immunofibers in aqueous solution with bioactive epitopes on the surface and have peptide or protein binding ability.
Type:
Grant
Filed:
August 17, 2018
Date of Patent:
September 5, 2023
Assignees:
THE JOHNS HOPKINS UNIVERSITY, BRISTOL-MYERS SQUIBB COMPANY
Inventors:
Honggang Cui, Yi Li, Lye Lin Lock, XuanKuo Xu, Zhengjian Li
Abstract: Provided herein are antibodies, or antigen binding portions thereof, that bind to OX40. Also provided are uses of these proteins in therapeutic applications, such as in the treatment of cancer. Further provided are cells that produce the antibodies, polynucleotides encoding the heavy and/or light chain variable region of the antibodies, and vectors comprising the polynucleotides encoding the heavy and/or light chain variable region of the antibodies.
Type:
Application
Filed:
August 11, 2022
Publication date:
August 31, 2023
Applicant:
Bristol-Myers Squibb Company
Inventors:
Zhehong CAI, Indrani CHAKRABORTY, Marie-Michelle Navarro GARCIA, Thomas D. KEMPE, Alan J. KORMAN, Alexander T. KOZHICH, Hadia LEMAR, Mark MAURER, Christina Maria MILBURN, Michael QUIGLEY, Xiang SHAO, Mohan SRINIVASAN, Kent THUDIUM, Susan Chien-Szu WONG, Jochem GOKEMEIJER, Xi-Tao WANG, Han CHANG, Patrick GUIRNALDA
Abstract: Disclosed are compounds of Formula (I) or salts thereof, wherein Ring Het, R1, R2, R3, R4, R5, m, n, and p are defined herein. Also disclosed are methods of using such compounds as inhibitors of signaling through Toll-like receptor 7, or 8, or 9, and pharmaceutical compositions comprising such compounds. These compounds are useful in treating inflammatory and autoimmune diseases.
Type:
Grant
Filed:
March 21, 2022
Date of Patent:
August 29, 2023
Assignee:
Bristol-Myers Squibb Company
Inventors:
Alaric J. Dyckman, Dharmpal S. Dodd, Christopher P. Mussari, Trevor C. Sherwood, John L. Gilmore, Tasir Shamsul Haque, Brian K. Whiteley, David R. Tortolani, Shoshana L. Posy, John E. Macor, Louis J. Lombardo, Ramesh Kumar Sistla, Anupama Kandhi Ramachandra Reddy, Subramanya Hegde, Laxman Pasunoori, Sreekantha Ratna Kumar
Abstract: The invention provides a method of treating a hepatocellular carcinoma with a LAG-3 antagonist alone or in combination with an additional therapeutic agent.
Type:
Application
Filed:
August 27, 2021
Publication date:
August 24, 2023
Applicant:
Bristol-Myers Squibb Company
Inventors:
Shivani SRIVASTAVA, Rebecca A. MOSS, Andrea HORVATH
Abstract: This provides pharmaceutical compositions that comprise (i) an anti-LAG-3 antibody or antigen binding fragment thereof or (ii) an anti-LAG-3 antibody or antigen binding fragment thereof and an anti-PD-1 antibody, anti-PD-L1 antibody, or antigen binding fragment thereof. Also provided are pharmaceutical compositions that comprise a buffering agent, stabilizing or bulking agent, and a surfactant. The disclosure also provides a vial, syringe, intravenous bag, or kit that comprises the compositions, and methods for using the compositions.
Type:
Grant
Filed:
May 30, 2018
Date of Patent:
August 15, 2023
Assignee:
Bristol-Myers Squibb Company
Inventors:
Lori S. Burton, William Ying, Nils Lonberg, Sudhir Chakravarthi, Pedro Smith
Abstract: Disclosed are compounds of Formula (I): or a salt thereof, wherein R1, R2, R4, R6, m, and n are defined herein. Also disclosed are methods of using such compounds to inhibit Helios protein, and pharmaceutical compositions comprising such compounds. These compounds are useful in the treatment of viral infections and proliferative disorders, such as cancer.
Abstract: Disclosed are compounds of Formula (I): or a salt thereof, wherein: R1, R2, R3, R4, R5, and m are defined herein. Also disclosed are methods of using such compounds to inhibit the activity of one or both of diacylglycerol kinase alpha (DGK?) and diacylglycerol kinase zeta (DGK?), and pharmaceutical compositions comprising such compounds. These compounds are useful in the treatment of viral infections and proliferative disorders, such as cancer.
Type:
Grant
Filed:
February 1, 2021
Date of Patent:
August 1, 2023
Assignee:
Bristol-Myers Squibb Company
Inventors:
Upender Velaparthi, Louis S. Chupak, Chetan Padmakar Darne, Min Ding, Robert G. Gentles, Yazhong Huang, Manjunatha Narayana Rao Kamble, Scott W. Martin, Raju Mannoori, Ivar M. McDonald, Richard E. Olson, Hasibur Rahaman, Prasada Rao Jalagam, Saumya Roy, Gopikishan Tonukunuru, Sivasudar Velaiah, Jayakumar Sankara Warrier, Xiaofan Zheng, John S. Tokarski, Bireshwar Dasgupta, Kotha Rathnakar Reddy, Thiruvenkadam Raja
Abstract: Disclosed are compounds of Formula (I): or a stereoisomer, a tautomer, or a salt or solvate thereof, wherein all the variables are as defined herein. These compounds modulate the activity of farnesoid X receptor (FXR), for example, as agonists. Also disclosed are pharmaceutical compositions comprising these compounds and methods of treating a disease, disorder, or condition associated with FXR dysregulation, such as pathological fibrosis, transplant rejection, cancer, osteoporosis, and inflammatory disorders, by using the compounds and pharmaceutical compositions.
Type:
Grant
Filed:
December 7, 2021
Date of Patent:
August 1, 2023
Assignee:
Bristol-Myers Squibb Company
Inventors:
Dean A. Wacker, Susheel Jethanand Nara, Srinivas Cheruku, Kandhasamy Sarkunam, Firoz Ali Jaipuri, Soodamani Thangavel, Srinivas Jogi, Pavan Kalyan Kathi
Abstract: The disclosure relates to compounds of Formulae (I)-(IX), which are formyl peptide 2 (FPR2) receptor agonists and/or formyl peptide 1 (FPR1) receptor agonists. The disclosure also provides compositions and methods of using the compounds, for example, for the treatment of atherosclerosis, heart failure, chronic obstructive pulmonary disease (COPD), and related diseases.
Type:
Grant
Filed:
August 12, 2021
Date of Patent:
July 25, 2023
Assignee:
Bristol-Myers Squibb Company
Inventors:
Pravin Sudhakar Shirude, Vishweshwaraiah Baligar, Balaji Seshadri, Amit Kumar Chattopadhyay, Nicholas R. Wurtz, Ellen K. Kick
Abstract: Disclosed are compounds of Formulas (I), (II), (III), (IV), and (V): and/or a salt thereof, wherein R1 is —OH or —OP(O)(OH)2, and X1, X2, X3, R2, R2a, Ra, Rb, and Rc are defined herein. Also disclosed are methods of using such compounds as selective agonists for G protein-coupled receptor S1P1, and pharmaceutical compositions comprising such compounds. These compounds are useful in treating, preventing, or slowing the progression of diseases or disorders in a variety of therapeutic areas, such as autoimmune diseases and vascular disease.
Type:
Grant
Filed:
May 4, 2021
Date of Patent:
July 18, 2023
Assignee:
Bristol-Myers Squibb Company
Inventors:
Alaric J. Dyckman, T. G. Murali Dhar, Hai-Yun Xiao, John L. Gilmore, Michael G. Yang, Zili Xiao, David Marcoux
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:
April 7, 2021
Date of Patent:
July 11, 2023
Assignee:
Bristol-Myers Squibb Company
Inventors:
Yan Shi, Peter Tai Wah Cheng, Ying Wang, Jun Shi, Shiwei Tao, Jun Li, Lawrence J. Kennedy, Robert F. Kaltenbach, III, Hao Zhang, James R. Corte
Abstract: Protein separation by capillary electrophoresis using a buffer composition comprising hydrophobic detergents that have alkyl chains longer than 12 carbon atoms. The formation of high molecular weight artifacts is suppressed.
Abstract: Methods of treating cancer with antibodies that bind colony stimulating factor 1 receptor (CSF1R) in combination with PD-1/PD-L1 inhibitors are provided.
Type:
Application
Filed:
December 21, 2022
Publication date:
July 6, 2023
Applicants:
Five Prime Therapeutics, Inc., Bristol-Myers Squibb Company
Inventors:
Brian Wong, Julie Hambleton, Robert Sikorski, Emma Masteller, Kevin Hestir, David Bellovin, Katherine E. Lewis