Abstract: A method for culturing eukaryotic cells for improved cell culture performance is provided. The method generally comprises propagating or maintaining eukaryotic cells in a defined cell culture medium; wherein the defined cell culture medium is supplemented with asparagine in an amount from about 2.6 mM to about 43.2 mM during early fed-batch cell culture and from about 2.6 mM to about 21.6 mM during late fed-batch cell culture; and maintaining said cells in said asparagine supplemented cell culture medium for at least a portion of the early fed-batch cell culture and at least a portion of the late fed-batch cell culture; wherein the performance of the cell culture is improved by the asparagine supplementation, as compared to a similar method with a lower amount of asparagine supplementation in the early and/or late fed-batch cell culture.
Type:
Grant
Filed:
August 27, 2021
Date of Patent:
December 10, 2024
Assignee:
Regeneron Pharmaceuticals, Inc.
Inventors:
Sandra Bennun-Serrano, Shawn M. Lawrence, Amy S. Johnson
Abstract: The present invention provides nucleic acid molecules that encode antibodies or antigen-binding fragments thereof, which specifically bind human interleukin-4 receptor (IL-4R). Also provided are expression vectors comprising nucleic acid molecule that encode anti-IL-4R antibodies, host cells comprising the expression vectors, and methods of producing anti-IL-4R antibodies or antigen-binding fragments thereof comprising growing the host cells under conditions permitting production of the antibody or fragment, and recovering the antibody or fragment so produced.
Type:
Grant
Filed:
October 6, 2020
Date of Patent:
December 10, 2024
Assignee:
REGENERON PHARMACEUTICALS, INC.
Inventors:
Joel H. Martin, Tammy T. Huang, Jeanette L. Fairhurst, Nicholas J. Papadopoulos, George D. Yancopoulos
Abstract: Methods of treating patients having varicose veins, methods of identifying subjects having an increased risk of developing varicose veins, and methods of diagnosing varicose veins in a human subject, comprising detecting the presence of Piezo Type Mechanosensitive Ion Channel Component 1 (PIEZO1) predicted loss-of-function variant nucleic acid molecules and polypeptides in a biological sample from the patient or subject, are provided herein.
Abstract: Genetically modified non-human animals and methods and compositions for making and using the same are provided, wherein the genetic modification comprises a humanization of an endogenous signal-regulatory protein gene, in particular a humanization of a SIRP? gene. Genetically modified mice are described, including mice that express a human or humanized SIRP? protein from an endogenous SIRP? locus.
Type:
Grant
Filed:
April 27, 2021
Date of Patent:
December 10, 2024
Assignee:
Regeneron Pharmaceuticals, Inc.
Inventors:
Andrew J. Murphy, O. Gavin Thurston, Bindu Varghese, Cagan Gurer
Abstract: The present disclosure relates to molecules capable of binding to both CD20 and PD1, as well as nucleic acids encoding such molecules, pharmaceutical compositions comprising such molecules, and methods of use thereof. In certain aspects, disclosed are CD20-PD1 binding molecules comprising at least one CD20 targeting moiety and at least one PD1 agonist moiety, where in certain aspects the PD1 agonist moiety is a PDL1 or PDL2 ectodomain or a PD1 binding portion thereof.
Type:
Application
Filed:
May 10, 2024
Publication date:
December 5, 2024
Applicant:
Regeneron Pharmaceuticals, Inc.
Inventors:
Yang SHEN, Bei WANG, Naga Suhasini AVVARU, Chia-Yang LIN, Andrew J. MURPHY
Abstract: Non-human animals, and methods and compositions for making and using the same, are provided, wherein the non-human animals comprise a humanization of a Lymphocyte activation gene 3 (Lag3). The non-human animals may be described, in some embodiments, as having a genetic modification to an endogenous Lag3 locus so that the non-human animals express a Lag3 polypeptide that includes a human portion and an endogenous portion (e.g., a non-human portion).
Type:
Application
Filed:
August 13, 2024
Publication date:
December 5, 2024
Applicant:
Regeneron Pharmaceuticals, Inc.
Inventors:
Alexander O. Mujica, Elena Burova, Andrew J. Murphy
Abstract: Improved capillary zone electrophoresis (CZE), affinity capillary electrophoresis (ACE), and partially filled-ACE (PF-ACE) systems and methods for the detection and quantification of specific molecular entities in a mixture thereof are provided. During manufacturing, heterodimeric bispecific antibodies are often produced along with homodimer species, which can confound quantification of the bispecific antibody. Disclosed are capillary electrophoretic systems and methods of detecting a specific homodimer in the mixture of bispecific heterodimer and homodimers. A ligand capable of binding one of the subunits of the bispecific antibody is contacted with the mixture to form a complex having a reduced electrophoretic mobility, thereby enabling detection of the unbound homodimer.
Abstract: A method for characterizing or quantifying one or more proteins in visible and/or sub-visible particles formed in a sample by detecting the at least one visible or sub-visible particle in the sample, isolating and capturing the at least one visible or sub-visible particle to identify a presence of a protein, and using a mass spectrometer to characterize the protein.
Abstract: A bispecific antibody format providing ease of isolation is provided, comprising immunoglobulin heavy chain variable domains that are differentially modified in the CH3 domain, wherein the differential modifications are non-immunogenic or substantially non-immunogenic with respect to the CH3 modifications, and at least one of the modifications results in a differential affinity for the bispecific antibody for an affinity reagent such as Protein A, and the bispecific antibody is isolable from a disrupted cell, from medium, or from a mixture of antibodies based on its affinity for Protein A.
Type:
Grant
Filed:
October 7, 2021
Date of Patent:
December 3, 2024
Assignee:
Regeneron Pharmaceuticals, Inc.
Inventors:
Samuel Davis, Eric Smith, Douglas MacDonald, Kara Louise Olson
Abstract: The present disclosure provides methods of identifying unreliable biological samples that may be mislabeled or contaminated, by determining the heteroplasmy and homoplasmy of mitochondrial DNA present in the biological samples.
Abstract: A method of purification and/or separation of glycopeptides and quantitation of same. The method includes contacting a sample comprising glycopeptides to a hydrophilic enrichment substrate under conditions that permit the glycopeptides to bind to the hydrophilic enrichment substrate. The glycopeptides are eluted from the hydrophilic enrichment substrate with an ammonium formate and acetonitrile (ACN) in water solution to create an enriched glycopeptide sample, which may be subjected to analysis to identify specific glycopeptides.
Abstract: The present disclosure provides methods of treating subjects having uveitis, and methods of identifying subjects having an increased risk of developing uveitis.
Type:
Grant
Filed:
October 13, 2022
Date of Patent:
December 3, 2024
Assignee:
Regeneron Pharmaceuticals, Inc.
Inventors:
Sahar Gelfman, Ann Ligocki, Giovanni Coppola, Aris Baras, Arden Moscati, Eli A. Stahl, Carmelo Romano, Santiago Mendez Huergo, Jonathan Weyne, Tave Van Zyl
Abstract: Methods for improving engraftment of donor cells in a subject thereof are provided. Such methods can comprise providing donor cells that have been modified to express a first isoform of a target protein (e.g., interleukin-2 receptor subunit gamma (IL2RG)) that is functionally indistinguishable but immunologically distinguishable from a second isoform of the target protein, administering the donor cells to the subject, and then selectively inhibiting host cells in the subject based on their expression of the second isoform of the target protein, thereby improving engraftment of donor cells in the subject. Also provided are combinations for administration to a subject in need thereof, wherein the combination comprises (1) a population of donor cells modified to express a first isoform of a target protein (e.g., IL2RG) and (2) an antagonist (e.g.
Type:
Application
Filed:
August 9, 2024
Publication date:
November 28, 2024
Applicant:
Regeneron Pharmaceuticals, Inc.
Inventors:
Michael Moore, Casandra Panea, Matthew Sleeman, Andrew J. Murphy, George D. Yancopoulos, Liang Zhang, Annabel Romero Hernández
Abstract: Non-human animals, methods and compositions for making and using the same, are provided, wherein said non-human animals comprise a humanization of a Cluster of Differentiation 274 (CD274) gene. Such non-human animals may be described, in some embodiments, as having a genetic modification to an endogenous CD274 gene so that said non-human animals express a Programmed cell death ligand 1 (PD-L1) polypeptide that includes a human portion and an endogenous portion (e.g., a non-human portion).
Type:
Application
Filed:
August 15, 2024
Publication date:
November 28, 2024
Applicant:
Regeneron Pharmaceuticals, Inc.
Inventors:
Elena Burova, Yajun Tang, Ka-Man Venus Lai, Andrew J. Murphy
Abstract: The present invention provides monoclonal antibodies, or antigen-binding fragments thereof, that bind to Ebola virus glycoproteins, pharmaceutical compositions comprising the antibodies and methods of use. The antibodies of the invention are useful for inhibiting or neutralizing Ebola virus activity, thus providing a means of treating or preventing Ebola virus infection in humans. In some embodiments, the invention provides for use of one or more antibodies that bind to the Ebola virus for preventing viral attachment and/or entry into host cells. The antibodies of the invention may be used prophylactically or therapeutically and may be used alone or in combination with one or more other anti-viral agents or vaccines.
Type:
Grant
Filed:
November 9, 2022
Date of Patent:
November 26, 2024
Assignee:
Regeneron Pharmaceuticals, Inc.
Inventors:
Christos Kyratsous, William Olson, Peter Mason, Neil Stahl
Abstract: The invention relates to a chromatography system and method for assessing amount and/or purity of a multimeric protein in a sample, wherein the chromatography system comprises two different affinity chromatography matrices connected via a switch valve.
Type:
Grant
Filed:
August 16, 2019
Date of Patent:
November 26, 2024
Assignee:
REGENERON PHARMACEUTICALS, INC.
Inventors:
Michael Perrone, Audrey Rodriguez, Andrew Tustian, Hanne Bak
Abstract: B-cell maturation antigen (BCMA) is expressed on malignant plasma cells. The present invention provides BCMA-specific chimeric antigen receptors and cells expressing such chimeric antigen receptors. In certain embodiments, engineered cells expressing the chimeric antigen receptors of the present invention are capable of inhibiting the growth of tumors expressing BCMA. The engineered cells of the invention are useful for the treatment of diseases and disorders in which an upregulated or induced BCMA-targeted immune response is desired and/or therapeutically beneficial. For example, engineered cells expressing the BCMA-specific chimeric antigen receptors of the invention are useful for the treatment of various cancers, including multiple myeloma.
Type:
Grant
Filed:
July 18, 2019
Date of Patent:
November 26, 2024
Assignee:
Regeneron Pharmaceuticals, Inc.
Inventors:
David DiLillo, Frank Delfino, Kevin Bray, Thomas Craig Meagher, Jessica Kirshner, Olga Sineshchekova
Abstract: The present disclosure generally pertains to methods of identifying and quantitating host cell proteins (HCPs) in therapeutic protein development. In particular, the present invention generally pertains to methods of liquid chromatography-tandem mass spectrometry (LC-MS/MS) for unbiased identification and sensitive quantitation of HCPs in therapeutic protein development.
Abstract: The present disclosure generally provides for a method of assembling a medical device, comprising forming a first assembly comprising a main body, a needle mechanism, a sterile connector operatively connected with a portion of the needle mechanism and configured to receive a cartridge. The needle mechanism and the sterile connector form a fluid path assembly which attaches with the main body forming the first assembly. The method further includes forming a second assembly comprising a base end and a translation mechanism, the translation mechanism is configured to engage the cartridge, and combining the first assembly and the second assembly.