Abstract: The present invention is directed to compounds of the formula (I), 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:
October 9, 2018
Date of Patent:
May 30, 2023
Assignee:
BRISTOL-MYERS SQUIBB COMPANY
Inventors:
Brian E. Fink, Dharmpal S. Dodd, Yufen Zhao, Lan-Ying Qin, Zheming Ruan, Lalgudi S. Harikrishnan, Muthoni G. Kamau
Abstract: In accordance with the present invention, CHO cells expressing a recombinant polypeptide of interest are grown in media where the amino acids, vitamins, phosphate, lipids and/or antioxidant optimization is utilized to manipulate and/or control the protein quality attributes of the polypeptides. Polypeptides expressed in accordance with the present invention may be advantageously used in the preparation of pharmaceutical compositions.
Abstract: The invention relates to an improved process for synthesizing 6-(cyclopropaneamido)-4-((2-methoxy-3-(1-methyl-1H-1,2,4-triazol-3-yl)phenyl)amino)-N-(methyl-d3)pyridazine-3-carboxamide of the formula: Compound I is currently in clinical trials for the treatment of auto-immune and auto-inflammatory diseases such as psoriasis.
Type:
Grant
Filed:
December 22, 2020
Date of Patent:
May 16, 2023
Assignee:
Bristol-Myers Squibb Company
Inventors:
Bahar Inankur, Sergei Kolotuchin, Maxime C. D. Soumeillant, Daniel S. Treitler
Abstract: The present invention provides compounds of formula (I), formula (II) or formula (III), wherein all of the variables are as defined herein. These compounds are inhibitors of indoleamine 2,3-dioxygenase (IDO), which may be used as medicaments for the treatment of proliferative disorders, such as cancer, viral infections and/or autoimmune diseases.
Type:
Grant
Filed:
October 8, 2018
Date of Patent:
May 16, 2023
Assignee:
Bristol-Myers Squibb Company
Inventors:
James Aaron Balog, Emily Charlotte Cherney, Weifang Shan, David K. Williams, Liping Zhang
Abstract: Provided herein are methods for treating a patient having NASH who has been determined to have a particular threshold level of serum Pro-C3 (e.g., greater than 10 ng/ML) by administering to the patient a modified Fibroblast growth factor 21 (FGF-21) in an amount and with a frequency sufficient to treat NASH. Also provided are methods for monitoring responsiveness of a patient having NASH to treatment with a modified FGF-21, the method comprising: determining the serum Pro-C3 level in a blood sample from the patient obtained during or after treatment, wherein: a decreased serum Pro-C3 level in the blood sample from the patient obtained during or after treatment, as compared to the serum Pro-C3 level in a blood sample from the patient obtained prior to treatment with the modified FGF-21, indicates that the patient is responsive to treatment with the modified FGF-21.
Type:
Grant
Filed:
September 6, 2018
Date of Patent:
May 9, 2023
Assignee:
BRISTOL-MYERS SQUIBB COMPANY
Inventors:
Edgar Davidson Charles, III, Rose C. Christian, Yi Luo
Abstract: The present invention provides compounds of Formula (I): or stereoisomers, tautomers, or pharmaceutically acceptable salts or solvates thereof, wherein all the variables are as defined herein. These compounds are antagonists to ?v-containing integrins. This invention also relates to pharmaceutical compositions comprising these compounds and methods of treating a disease, disorder, or condition associated with dysregulation of ?v-containing integrins, such as pathological fibrosis, transplant rejection, cancer, osteoporosis, and inflammatory disorders, by using the compounds and pharmaceutical compositions.
Type:
Grant
Filed:
March 25, 2021
Date of Patent:
May 2, 2023
Assignee:
Bristol-Myers Squibb Company
Inventors:
Pratik Devasthale, Fang Moore, Guohua Zhao, Susan Nicole Pieniazek, Kumaravel Selvakumar, Suresh Dhanusu, Manoranjan Panda, Lawrence R. Marcin
Abstract: Compounds according to formula I are useful as agonists of Toll-like receptor 7 (TLR7). (I) Such compounds can be used in cancer treatment, especially in combination with an anti-cancer immunotherapy agent, or as a vaccine adjuvant.
Type:
Application
Filed:
January 26, 2021
Publication date:
April 20, 2023
Applicant:
BRISTOL-MYERS SQUIBB COMPANY
Inventors:
Yam B. POUDEL, Matthew COX, Liqi HE, Daniel O'MALLEY, Ashvinikumar V. GAVAI, Sanjeev GANGWAR, Matthias BROEKEMA, Prasanna SIVAPRAKASAM, Christine M. TARBY, Murugaiah ANDAPPAN MURUGAIAH SUBBAIAH,Murugaiah
Abstract: Provided are methods for clinical treatment of malignant tumors (e.g., advanced solid tumors) using a combination of an anti-LAG-3 antibody, an anti-PD-1 antibody, and an immunotherapeutic agent.
Type:
Application
Filed:
August 10, 2022
Publication date:
April 13, 2023
Applicant:
Bristol-Myers Squibb Company
Inventors:
Alan J. KORMAN, Nils LONBERG, Mark J. SELBY, Jeffrey JACKSON
Abstract: A prodrugged antibody has a blocking moiety attached to a Cys on its heavy or light chain via a linker having a cleavable moiety. The blocking moiety inhibits binding of the antibody to its antigen. Cleavage of the cleavable moiety releases the blocking moiety and restores ability of the antibody to bind to its antigen.
Type:
Grant
Filed:
August 14, 2018
Date of Patent:
April 11, 2023
Assignee:
Bristol-Myers Squibb Company
Inventors:
Stanley R. Krystek, Jr., Yong Zhang, Gregory D. Vite, Arvind Rajpal, Chetana Rao-Naik, Paul E. Morin, Mohan Srinivasan, Zheng Lin, Virginie Lafont, Alla Pritsker
Abstract: Disclosed are compounds of Formula (I): or a salt thereof, wherein: X is CR4 or N; R1, R2, R3, R4, and A are defined herein. Also disclosed are methods of using such compounds as inhibitors of Bruton's tyrosine kinase (Btk), 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:
December 3, 2020
Date of Patent:
April 11, 2023
Assignee:
Bristol-Myers Squibb Company
Inventors:
Qingjie Liu, Scott Hunter Watterson, John E. Macor, Khehyong Ngu, Saleem Ahmad
Abstract: The invention is a method of preventing the generation of pink color during antibody manufacturing by either preventing the reduction of antibodies during manufacturing and harvest or inhibiting the conversion of cyanocobalamin (CN-Cbl) to hydroxocobalamin (HO-Cbl) during manufacturing and harvest. Replacement of white light in the cell culture media preparation and storage areas with red light inhibits the conversion of CN-Cbl to HO-Cbl. Addition of peroxides to the clarified bulk at harvest inhibits reduction of the antibody disulfide bonds.
Type:
Application
Filed:
May 8, 2018
Publication date:
April 6, 2023
Applicant:
BRISTOL-MYERS SQUIBB COMPANY
Inventors:
Cheng DU, Ameya Umesh BORWANKAR, Joon Chong YEE, Zhijun TAN
Abstract: The disclosure relates to compounds of formula I which are useful as kinase modulators including RIPK 1 modulation. The disclosure also provides methods of making and using the compounds for example in treatments related to necrosis or inflammation as well as other indications.
Type:
Grant
Filed:
January 24, 2019
Date of Patent:
April 4, 2023
Assignee:
Bristol-Myers Squibb Company
Inventors:
Scott Hunter Watterson, Murugaiah Andappan Murugaiah Subbaiah, Carolyn Diane Dzierba, Hua Gong, Jason M. Guernon, Junqing Guo, Amy C. Hart, Guanglin Luo, John E. Macor, William J. Pitts, Jianliang Shi, Brian Lee Venables, Carolyn A. Weigelt, Yong-Jin Wu, Zhizhen Barbara Zheng, Sing-Yuen Sit, Jie Chen
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:
Application
Filed:
April 20, 2022
Publication date:
March 30, 2023
Applicant:
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: Disclosed is crystalline Form B of 6-(cyclopropanecarboxamido)-4-((2-methoxy-3-(1-methy-1H-1,2,4-triazol-3-yl)phenyl) amino)-N-methyl-d3)pyridazine-3-carboxamide. Form B is the HCl salt of a neat crystalline form. Characterization data for Form B are disclosed.
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:
Grant
Filed:
December 23, 2021
Date of Patent:
March 28, 2023
Assignee:
Bristol-Myers Squibb Company
Inventors:
Aaron Yamniuk, Mary Struthers, Suzanne J. Suchard
Abstract: This provides pharmaceutical compositions that comprise a combination of an anti-cancer agent which is an first antibody and a second antibody. In some embodiments, the first antibody is an anti-Programmed Death-1 (PD-1) antibody. In certain embodiments, the composition is a fixed dose formulation. In certain embodiments, the composition is administered as a flat-dose. The disclosure also provides a kit for treating a subject afflicted with a disease, the kit comprising a dosage of any composition disclosed herein and instructions for using the composition in any of the disclosed methods for treating a disease.
Abstract: The present invention relates to novel phosphorous (V) (P(V)) reagents, methods for preparing thereof, and methods for preparing organophosphorous (V) compounds by using the novel reagents.
Type:
Grant
Filed:
April 12, 2019
Date of Patent:
March 28, 2023
Assignees:
Bristol-Myers Squibb Company, The Scripps Research Institute
Inventors:
Michael Anthony Schmidt, Bin Zheng, Kyle Knouse, Justine deGruyter, Martin D. Eastgate, Phil Baran, William R. Ewing, Richard E. Olson, Ivar M. McDonald
Abstract: The present disclosure provides fusion proteins comprising an IL-10 polypeptide and a second polypeptide, e.g., an Fc polypeptide. Certain aspects of the present disclosure are directed to methods of treating a subject comprising administering the IL-10 fusion protein. In certain aspects, the subject is afflicted with a cancer.
Type:
Application
Filed:
February 5, 2021
Publication date:
March 23, 2023
Applicant:
BRISTOL-MYERS SQUIBB COMPANY
Inventors:
Shodeinde COKER, Robert F. GRAZIANO, Murali GURURAJAN, Kanstantsin V. KATLINSKI, James K. LOY, Paul E. MORIN, Brian A. POIRSON, Vanessa M. SPIRES, Zheng YANG
Abstract: The present invention relates to the use of online biomass capacitance monitoring in cultures as a way to control the growth of cells through the use of a temperature control loop. In certain embodiments, a biomass capacitance probe is used to measure the cell density, and a predetermined growth curve is used to adjust the temperature in the culture.
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 arc 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.