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    OFF-TARGET PREDICTION METHOD FOR ANTIGEN-RECOGNITION MOLECULES BINDING TO MHC-PEPTIDE TARGETS
    1.
    发明申请
    OFF-TARGET PREDICTION METHOD FOR ANTIGEN-RECOGNITION MOLECULES BINDING TO MHC-PEPTIDE TARGETS 有权

    公开(公告)号：US20250014675A1

    公开(公告)日：2025-01-09

    申请号：US18749036

    申请日：2024-06-20

    Applicant: Regeneron Pharmaceuticals, Inc.

    Inventor： Ankur Dhanik ,  Kunal Kundu ,  Wen-yi Lee ,  David Suh ,  Gang Chen ,  Robert Salzler ,  Robert Babb

    IPC: G16B15/30 ,  C12N15/10 ,  G01N33/564

    Abstract: Computational systems and methods for predicting amino acid position(s) within a target peptide presented in a complex with a major histocompatibility complex (MHC) molecule (MHC-target peptide complex), the amino acid position(s) being involved in interacting with an antigen-recognition molecule that recognizes said MHC-target peptide complex, are presented herein. Computational systems and methods for estimating a number of off-target peptide(s) for an antigen-recognition molecule that recognizes a target peptide presented in a complex with a major histocompatibility complex (MHC) molecule (MHC-target peptide complex) is presented herein. Computational systems and methods for ranking potential target peptides to mitigate off-target toxicity are presented herein. Such computational systems and methods can streamline development of effective, well tolerated antigen-recognition molecules to treat diseases.

    Optimized Anti-CD3 Bispecific Antibodies and Uses Thereof
    4.
    发明申请
    Optimized Anti-CD3 Bispecific Antibodies and Uses Thereof 有权

    公开(公告)号：US20210253701A1

    公开(公告)日：2021-08-19

    申请号：US17207462

    申请日：2021-03-19

    Applicant: Regeneron Pharmaceuticals, Inc.

    Inventor： Eric Smith ,  Lauric Haber ,  Robert Babb ,  Gang Chen ,  Douglas MacDonald

    IPC: C07K16/28 ,  C07K16/30 ,  A61P35/00 ,  C07K16/40 ,  C07K16/46

    Abstract: The present invention provides antibodies that bind to CD3 with weak or no detectable binding affinity and methods of using the same. According to certain embodiments, the antibodies of the invention bind human CD3 with low affinity and induce human T cell proliferation and hence induce T cell-mediated killing of tumor cells with high efficacy. According to certain embodiments, the present invention provides bispecific antigen-binding molecules comprising a first antigen-binding domain that specifically binds human CD3 with weak or no detectable binding affinity in an in vitro assay, and a second antigen-binding molecule that specifically binds human tumor-associated antigen. In certain embodiments, the bispecific antigen-binding molecules of the present invention are capable of inhibiting the growth of tumors expressing target antigen, such as PSMA. The antibodies and bispecific antigen-binding molecules of the invention are useful for the treatment of diseases and disorders in which an upregulated or induced targeted immune response is desired and/or therapeutically beneficial. For example, the antibodies of the invention are useful for the treatment of various cancers or other diseases where immunotherapy, i.e. effector cell immunomodulation is warranted.

    Isolating Cells Expressing Secreted Proteins
    5.
    发明申请
    Isolating Cells Expressing Secreted Proteins 审中-公开

    公开(公告)号：US20190376981A1

    公开(公告)日：2019-12-12

    申请号：US16352154

    申请日：2019-03-13

    Applicant: Regeneron Pharmaceuticals, Inc.

    Inventor： James P. Fandl ,  Gang Chen ,  Neil Stahl ,  George D. Yancopoulos

    IPC: G01N33/68 ,  G01N33/566 ,  C12N15/65 ,  G01N33/569

    Abstract: A method of detecting and isolating cells that produce a secreted protein of interest (POI), for example, an antibody, comprising: a) providing a eukaryotic cell comprising (i) a nucleic acid encoding the POI, and (ii) a nucleic acid encoding a cell surface capture molecule, which comprises a membrane anchor and is capable of binding the POI; (b) culturing the cell under conditions in which the POI and cell surface capture molecule are expressed, and a POI-cell surface capture molecule complex is formed intracellularly and displayed on the cell surface; c) detecting the surface-displayed POI by contacting the cells with a detection molecule, which binds the POI; and d) isolating cells based on the detection molecule.

    Production cell line enhancers
    7.
    发明授权
    Production cell line enhancers 有权

    公开(公告)号：US10351622B2

    公开(公告)日：2019-07-16

    申请号：US15624982

    申请日：2017-06-16

    Applicant: Regeneron Pharmaceuticals, Inc.

    Inventor： Gang Chen ,  Darya Burakov ,  Dipali Deshpande

    IPC: C07K16/22 ,  C12N15/85 ,  C07K14/47 ,  C12N15/79 ,  C07K16/00 ,  C12N9/24 ,  C12N15/09 ,  C12N15/63

    Abstract: The present invention relates to discovery of the ectopic expression of EDEM2 in a production cell to improve the yield of a useful multi-subunit protein. Thus, the present invention provides for production cell lines, such as the canonical mammalian biopharmaceutical production cell, the CHO cell, containing recombinant polynucleotides encoding EDEM2. Also disclosed is a production cell containing both an EDEM2-encoding polynucleotide as well an XBP1-encoding polynucleotide. Improved titers of antibodies produced by these cell lines are disclosed, as well as the improved cell densities attained by these cells in culture.

    Optimized Anti-CD3 Bispecific Antibodies and Uses Thereof
    8.
    发明申请
    Optimized Anti-CD3 Bispecific Antibodies and Uses Thereof 审中-公开

    公开(公告)号：US20180355038A1

    公开(公告)日：2018-12-13

    申请号：US15780504

    申请日：2016-09-23

    Applicant: Regeneron Pharmaceuticals, Inc.

    Inventor： Eric Smith ,  Lauric Haber ,  Robert Babb ,  Gang Chen ,  Douglas MacDonald

    IPC: C07K16/28 ,  C07K16/46 ,  C07K16/30 ,  C07K16/40 ,  A61P35/00

    CPC classification number: C07K16/2809 ,  A61K2039/505 ,  A61P35/00 ,  C07K16/2863 ,  C07K16/3069 ,  C07K16/40 ,  C07K16/468 ,  C07K2317/31 ,  C07K2317/55 ,  C07K2317/92

    Abstract: The present invention provides antibodies that bind to CD3 with weak or no detectable binding affinity and methods of using the same. According to certain embodiments, the antibodies of the invention bind human CD3 with low affinity and induce human T cell proliferation and hence induce T cell-mediated killing of tumor cells with high efficacy. According to certain embodiments, the present invention provides bispecific antigen-binding molecules comprising a first antigen-binding domain that specifically binds human CD3 with weak or no detectable binding affinity in an in vitro assay, and a second antigen-binding molecule that specifically binds human tumor-associated antigen. In certain embodiments, the bispecific antigen-binding molecules of the present invention are capable of inhibiting the growth of tumors expressing target antigen, such as PSMA. The antibodies and bispecific antigen-binding molecules of the invention are useful for the treatment of diseases and disorders in which an upregulated or induced targeted immune response is desired and/or therapeutically beneficial. For example, the antibodies of the invention are useful for the treatment of various cancers or other diseases where immunotherapy, i.e. effector cell immunomodulation is warranted.

    Fucosylation-deficient cells
    10.
    发明授权
    Fucosylation-deficient cells 有权
    岩藻糖基化缺陷型细胞

    公开(公告)号：US09206455B2

    公开(公告)日：2015-12-08

    申请号：US13779952

    申请日：2013-02-28

    Applicant: Regeneron Pharmaceuticals, Inc.

    Inventor： Gang Chen ,  Darya Burakov ,  James P. Fandl

    IPC: C12N9/02 ,  C12N15/00 ,  C12N1/20 ,  C07H21/04 ,  C12P21/00 ,  C07K16/00 ,  C07K16/28 ,  C12N9/04

    CPC classification number: C12P21/005 ,  C07K16/00 ,  C07K16/2863 ,  C07K16/2866 ,  C07K2317/14 ,  C07K2317/41 ,  C12N9/0006 ,  C12N15/00 ,  C12Y101/01271 ,  Y02P20/52

    Abstract: An isolated nucleic acid encoding an FX protein having a serine at position 79, a lysine at position 90, a leucine at position 136, an arginine at position 211, a serine at position 289, and a combination thereof is provided. Cells having a gene encoding a modified FX protein are provided, wherein the cells exhibit a reduced ability to fucosylate a glycoprotein at a first temperature, but exhibit the ability to fucosylate the glycoprotein at a second temperature. Methods and compositions for making glycoproteins with reduced fucosylation are provided.

    Abstract translation: 提供了编码FX蛋白的分离核酸，其在79位具有丝氨酸，在90位具有赖氨酸，136位的亮氨酸，211位的精氨酸，289位的丝氨酸及其组合。 提供具有编码经修饰的FX蛋白的基因的细胞，其中细胞在第一温度下表现出降低糖蛋白岩藻糖化能力，但在第二温度下表现出对糖蛋白的岩藻糖化能力。 提供了用于制备具有降低的岩藻糖基化的糖蛋白的方法和组合物。

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