Patents Assigned to E.R. SQUIBB & SONS, L.L.C.
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Patent number: 12157757Abstract: The present invention provides improved methods of protein purification using CEX chromatography. Such methods generally comprise the steps of: contacting a protein of interest (e.g., an antibody) with a cation exchange resin at a first pH, that is less than the pI of the most acidic isoform of the protein of interest, such that the protein of interest binds to the resin; washing the cation exchange resin at a second pH that is greater than the first pH, but less than the pI of the most acidic isoform of the protein of interest; and eluting the protein of interest from the resin at a third pH that is about equal to or less than the first pH. The methods of the invention are particularly useful for the commercial purification of recombinant therapeutic proteins (e.g., antibodies).Type: GrantFiled: February 24, 2022Date of Patent: December 3, 2024Assignee: E.R. SQUIBB & SONS, L.L.C.Inventors: Alahari Arunakumari, Jue Wang
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Publication number: 20230272079Abstract: The present invention provides isolated monoclonal antibodies, particularly human monoclonal antibodies, that specifically bind to PD-1 with high affinity. 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 detecting PD-1, as well as methods for treating various diseases, including cancer and infectious diseases, using anti-PD-1 antibodies. The present invention further provides methods for using a combination immunotherapy, such as the combination of anti-CTLA-4 and anti-PD-1 antibodies, to treat hyperproliferative disease, such as cancer. The invention also provides methods for altering adverse events related to treatment with such antibodies individually.Type: ApplicationFiled: February 9, 2023Publication date: August 31, 2023Applicants: E.R. SQUIBB & SONS, L.L.C., Ono Pharmaceutical Co., LTD.Inventors: Alan J. KORMAN, Mohan SRINIVASAN, Changyu WANG, Mark J. SELBY, Bingliang CHEN, Josephine M. CARDARELLI, Haichun HUANG
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Publication number: 20230061544Abstract: The present disclosure provides isolated monoclonal antibodies, particularly human monoclonal antibodies that specifically bind to PD-L1 with high affinity. Nucleic acid molecules encoding the antibodies of this disclosure, expression vectors, host cells and methods for expressing the antibodies of this disclosure are also provided. Immunoconjugates, bispecific molecules and pharmaceutical compositions comprising the antibodies of the invention are also provided. The disclosure also provides methods for detecting PD-L1, as well as methods for treating various diseases, including cancer and infectious diseases, using anti-PD-L1 antibodies.Type: ApplicationFiled: June 16, 2022Publication date: March 2, 2023Applicant: E.R. Squibb & Sons, L. L. C.Inventors: Alan J. KORMAN, Mark J. SELBY, Changyu WANG, Mohan SRINIVASAN, David B. PASSMORE, Haichun HUANG, Haibin CHEN
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Publication number: 20220403046Abstract: The present disclosure provides isolated monoclonal antibodies, particularly human monoclonal antibodies that specifically bind to Fucosyl-GM1 with high affinity. Nucleic acid molecules encoding the antibodies of this disclosure, expression vectors, host cells and methods for expressing the antibodies of this disclosure are also provided. Immunoconjugates, bispecific molecules and pharmaceutical compositions comprising the antibodies of this disclosure are also provided. This disclosure also provides methods for detecting Fucosyl-GM1, as well as methods for treating various diseases, including cancer, using anti-Fucosyl-GM1 antibodies.Type: ApplicationFiled: August 5, 2022Publication date: December 22, 2022Applicant: E. R. SQUIBB & SONS, L.L.C.Inventors: Cynthia A. VISTICA, Eric H. HOLMES, Peter BRAMS, Alison WITTE, Josephine M. CARDARELLI
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Patent number: 11530267Abstract: The present disclosure provides isolated monoclonal antibodies that specifically bind to LAG-3 with high affinity, particularly human monoclonal antibodies. Preferably, the antibodies bind human LAG-3. In certain embodiments, the antibodies bind both human and monkey LAG-3 but do not bind mouse LAG-3. The invention provides anti-LAG-3 antibodies that can inhibit the binding of LAG-3 to WIC Class II molecules and that can stimulate antigen-specific T cell responses. 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. This disclosure 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.Type: GrantFiled: December 7, 2021Date of Patent: December 20, 2022Assignee: E.R. Squibb & Sons, L.L.C.Inventors: Kent B. Thudium, Mark J. Selby, Kyra D. Zens, Mark Yamanaka, Alan J. Korman, Heidi N. Leblanc
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Patent number: 11512130Abstract: The present disclosure provides isolated monoclonal antibodies that specifically bind to LAG-3 with high affinity, particularly human monoclonal antibodies. Preferably, the antibodies bind human LAG-3. In certain embodiments, the antibodies bind both human and monkey LAG-3 but do not bind mouse LAG-3. The invention provides anti-LAG-3 antibodies that can inhibit the binding of LAG-3 to MHC Class II molecules and that can stimulate antigen-specific T cell responses. 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. This disclosure 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.Type: GrantFiled: December 7, 2021Date of Patent: November 29, 2022Assignee: E.R. Squibb & Sons, L.L.C.Inventors: Kent B. Thudium, Mark J. Selby, Kyra D. Zens, Mark Yamanaka, Alan J. Korman, Heidi N. Leblanc
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Patent number: 11384363Abstract: The instant invention relates to transgenic non-human animals capable of producing heterologous antibodies, transgenes used to produce such transgenic animals, transgenes capable of functionally rearranging a heterologous D gene in V-D-J recombination, immortalized B-cells capable of producing heterologous antibodies, methods and transgenes for producing heterologous antibodies of multiple isotypes, methods and transgenes for producing heterologous antibodies wherein a variable region sequence comprises somatic mutation as compared to germline rearranged variable region sequences, transgenic nonhuman animals which produce antibodies having a human primary sequence and which bind to human antigens, hybridomas made from B cells of such transgenic animals, and monoclonal antibodies expressed by such hybridomas.Type: GrantFiled: June 2, 2017Date of Patent: July 12, 2022Assignee: E.R. Squibb & Sons, L.L.C.Inventors: Daniel K. Rohrer, Amelia N. Black, Nils Lonberg
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Patent number: 11292814Abstract: The present invention provides improved methods of protein purification using CEX chromatography. Such methods generally comprise the steps of: contacting a protein of interest (e.g., an antibody) with a cation exchange resin at a first pH, that is less than the pI of the most acidic isoform of the protein of interest, such that the protein of interest binds to the resin; washing the cation exchange resin at a second pH that is greater than the first pH, but less than the pI of the most acidic isoform of the protein of interest; and eluting the protein of interest from the resin at a third pH that is about equal to or less than the first pH. The methods of the invention are particularly useful for the commercial purification of recombinant therapeutic proteins (e.g., antibodies).Type: GrantFiled: April 20, 2018Date of Patent: April 5, 2022Assignee: E.R. SQUIBB & SONS, L.L.C.Inventors: Alahari Arunakumari, Jue Wang
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Patent number: 11236163Abstract: The present disclosure provides isolated monoclonal antibodies that specifically bind to LAG-3 with high affinity, particularly human monoclonal antibodies. Preferably, the antibodies bind human LAG-3. In certain embodiments, the antibodies bind both human and monkey LAG-3 but do not bind mouse LAG-3. The invention provides anti-LAG-3 antibodies that can inhibit the binding of LAG-3 to MHC Class II molecules and that can stimulate antigen-specific T cell responses. 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. This disclosure 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.Type: GrantFiled: April 9, 2021Date of Patent: February 1, 2022Assignee: E.R. Squibb & Sons, L.L.C.Inventors: Kent B. Thudium, Mark J. Selby, Kyra D. Zens, Mark Yamanaka, Alan J. Korman, Heidi N. Leblanc
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Patent number: 11236164Abstract: The present disclosure provides isolated monoclonal antibodies that specifically bind to LAG-3 with high affinity, particularly human monoclonal antibodies. Preferably, the antibodies bind human LAG-3. In certain embodiments, the antibodies bind both human and monkey LAG-3 but do not bind mouse LAG-3. The invention provides anti-LAG-3 antibodies that can inhibit the binding of LAG-3 to WIC Class II molecules and that can stimulate antigen-specific T cell responses. 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. This disclosure 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.Type: GrantFiled: April 9, 2021Date of Patent: February 1, 2022Assignee: E.R. Squibb & Sons, L.L.C.Inventors: Kent B. Thudium, Mark J. Selby, Kyra D. Zens, Mark Yamanaka, Alan J. Korman, Heidi N. Leblanc
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Patent number: 11236165Abstract: The present disclosure provides isolated monoclonal antibodies that specifically bind to LAG-3 with high affinity, particularly human monoclonal antibodies. Preferably, the antibodies bind human LAG-3. In certain embodiments, the antibodies bind both human and monkey LAG-3 but do not bind mouse LAG-3. The invention provides anti-LAG-3 antibodies that can inhibit the binding of LAG-3 to WIC Class II molecules and that can stimulate antigen-specific T cell responses. 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. This disclosure 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.Type: GrantFiled: April 9, 2021Date of Patent: February 1, 2022Assignee: E.R. Squibb & Sons, L.L.C.Inventors: Kent B. Thudium, Mark J. Selby, Kyra D. Zens, Mark Yamanaka, Alan J. Korman, Heidi N. Leblanc
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Patent number: 11072664Abstract: The present invention provides isolated human monoclonal antibodies that bind to IFNAR-1 and that are capable of inhibiting the biological activity of Type I interferons. Immunoconjugates, bispecific molecules and pharmaceutical compositions comprising the antibodies of the invention are also provided. The invention also provides methods for inhibiting Type I interferon-mediated disorders using the antibodies of the invention, including methods for treating autoimmune disorders, transplant rejection or Graft Versus Host Disease using the antibodies of the invention.Type: GrantFiled: July 3, 2019Date of Patent: July 27, 2021Assignee: E.R. Squibb & Sons, L.L.C.Inventors: Josephine M. Cardarelli, Alison Witte, Mohan Srinivasan
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Patent number: 11001630Abstract: The present disclosure provides isolated monoclonal antibodies that specifically bind to LAG-3 with high affinity, particularly human monoclonal antibodies. Preferably, the antibodies bind human LAG-3. In certain embodiments, the antibodies bind both human and monkey LAG-3 but do not bind mouse LAG-3. The invention provides anti-LAG-3 antibodies that can inhibit the binding of LAG-3 to WIC Class II molecules and that can stimulate antigen-specific T cell responses. 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. This disclosure 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.Type: GrantFiled: August 21, 2020Date of Patent: May 11, 2021Assignee: E.R. Squibb & Sons, L.L.C.Inventors: Kent B. Thudium, Mark J. Selby, Kyra D. Zens, Mark Yamanaka, Alan J. Korman, Heidi N. LeBlanc
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Patent number: 10988535Abstract: The present disclosure provides isolated monoclonal antibodies that specifically bind to LAG-3 with high affinity, particularly human monoclonal antibodies. Preferably, the antibodies bind human LAG-3. In certain embodiments, the antibodies bind both human and monkey LAG-3 but do not bind mouse LAG-3. The invention provides anti-LAG-3 antibodies that can inhibit the binding of LAG-3 to MHC Class II molecules and that can stimulate antigen-specific T cell responses. 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. This disclosure 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.Type: GrantFiled: May 22, 2019Date of Patent: April 27, 2021Assignee: E.R. Squibb & Sons, L.L.C.Inventors: Kent B. Thudium, Mark J. Selby, Kyra D. Zens, Mark Yamanaka, Alan J. Korman, Heidi N. Leblanc
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Patent number: 10988536Abstract: The present disclosure provides isolated monoclonal antibodies that specifically bind to LAG-3 with high affinity, particularly human monoclonal antibodies. Preferably, the antibodies bind human LAG-3. In certain embodiments, the antibodies bind both human and monkey LAG-3 but do not bind mouse LAG-3. The invention provides anti-LAG-3 antibodies that can inhibit the binding of LAG-3 to MHC Class II molecules and that can stimulate antigen-specific T cell responses. 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. This disclosure 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.Type: GrantFiled: August 21, 2020Date of Patent: April 27, 2021Assignee: E.R. Squibb & Sons, L.L.C.Inventors: Kent B. Thudium, Mark J. Selby, Kyra D. Zens, Mark Yamanaka, Alan J. Korman, Heidi N. Leblanc
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Publication number: 20200231671Abstract: The present disclosure provides isolated monoclonal antibodies that specifically bind to LAG-3 with high affinity, particularly human monoclonal antibodies. Preferably, the antibodies bind human LAG-3. In certain embodiments, the antibodies bind both human and monkey LAG-3 but do not bind mouse LAG-3. The invention provides anti-LAG-3 antibodies that can inhibit the binding of LAG-3 to MHC Class II molecules and that can stimulate antigen-specific T cell responses. 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. This disclosure 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.Type: ApplicationFiled: December 20, 2019Publication date: July 23, 2020Applicant: E.R. Squibb & Sons, L.L.C.Inventors: Kent B. THUDIUM, Mark J. SELBY, Kyra D. ZENS, Mark YAMANAKA, Alan J. KORMAN, Heidi N. LEBLANC
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Publication number: 20200138945Abstract: The present invention provides isolated monoclonal antibodies, particularly human monoclonal antibodies, that specifically bind to PD-1 with high affinity. 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 detecting PD-1, as well as methods for treating various diseases, including cancer and infectious diseases, using anti-PD-1 antibodies. The present invention further provides methods for using a combination immunotherapy, such as the combination of anti-CTLA-4 and anti-PD-1 antibodies, to treat hyperproliferative disease, such as cancer. The invention also provides methods for altering adverse events related to treatment with such antibodies individually.Type: ApplicationFiled: October 11, 2019Publication date: May 7, 2020Applicants: E.R. SQUIBB & SONS, L.L.C., Ono Pharmaceutical Co., LTD.Inventors: Alan J. Korman, Mohan Srinivasan, Changyu Wang, Mark J. Selby, Bingliang Chen, Josephine M. Cardarelli, Haichun Huang
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Publication number: 20200062848Abstract: The present disclosure provides isolated monoclonal antibodies, particularly human monoclonal antibodies that specifically bind to PD-L1 with high affinity. Nucleic acid molecules encoding the antibodies of this disclosure, expression vectors, host cells and methods for expressing the antibodies of this disclosure are also provided. Immunoconjugates, bispecific molecules and pharmaceutical compositions comprising the antibodies of the invention are also provided. The disclosure also provides methods for detecting PD-L1, as well as methods for treating various diseases, including cancer and infectious diseases, using anti-PD-L1 antibodies.Type: ApplicationFiled: June 21, 2019Publication date: February 27, 2020Applicant: E.R. Squibb & Sons, L. L. C.Inventors: Alan J. KORMAN, Mark J. SELBY, Changyu WANG, Mohan SRINIVASAN, David B. PASSMORE, Haichun HUANG, Haibin CHEN
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Patent number: 10501556Abstract: Methods for treating a cocaine-related disorder in an individual include administering to the individual a therapeutic amount of an antibody comprising a human immunoglobulin gamma heavy chain and a murine lambda light chain. In another embodiment, the light chain includes a human kappa light chain at least partially derived from 1B3. Other embodiments are directed toward the antibodies themselves and methods of binding the antibodies.Type: GrantFiled: August 15, 2017Date of Patent: December 10, 2019Assignees: University of Cincinnati, E. R. Squibb & Sons, L.L.C.Inventors: Andrew B. Norman, William J. Ball, Jr., Nils Lonberg, Denise Williams
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Patent number: 10448622Abstract: The present invention relates to a human artificial chromosome which is genetically transmissible to the next generation with high efficiency and the method for using the same. More specifically, the present invention relates to: a human artificial chromosome in which an about 3.5 Mb to about 1 Mb region containing an antibody ? light chain gene derived from human chromosome 22 is bound to a chromosome fragment which is transmissible to a progeny through a germ line of a non-human animal, said chromosome fragment is derived from another human chromosome; a non-human animal carrying the human artificial chromosome and an offspring thereof; a method for producing the non-human animal; a method for producing a human antibody using the nonhuman animal or an offspring thereof; and a human antibody-producing mouse carrying the human artificial chromosome.Type: GrantFiled: October 19, 2016Date of Patent: October 22, 2019Assignees: E. R. Squibb & Sons, L.L.C., Kyowa Hakko Kirin Co., LtdInventors: Yoshimi Kuroiwa, Kazuma Tomizuka, Hitoshi Yoshida, Isao Ishida