Abstract: Methods of culturing cells capable of producing desired proteins to obtain the proteins by use of a medium from which biological components are excluded as much as possible are provided. Specifically, a culture method characterized by culturing while maintaining a specific amino acid in a culture solution at a high concentration, and a cell culture fed-batch medium for use in the method are provided.
Abstract: The present invention relates to anti-HLA-DQ2.5 antibodies and its use for the treatment of celiac disease. The present invention provides anti-HLA-DQ2.5 antibodies that have been modified. The anti-HLA-DQ2.5 antibodies of the invention have binding activity to complexes formed by HLA-DQ2.5 and a gluten peptide, but have substantially no binding activity to complexes formed by HLA-DQ2.5 and an irrelevant peptide. Furthermore, the antibodies of the invention are shown to have inhibitory effects on T cell activation by gluten peptides.
Abstract: The present inventors have successfully prepared an antigen-binding molecule comprising an antibody variable region that has binding activity against a molecule expressed on the surface of a T cell and a molecule expressed on the surface of any other immunocyte, but does not bind to these molecules at the same time. The present invention allows the preparation of an antigen-binding molecule capable of circumventing adverse reactions that may be caused by the cross-linking of T cells to other immunocytes, and provides an antigen-binding molecule suitable as a drug.
Type:
Grant
Filed:
December 5, 2019
Date of Patent:
August 29, 2023
Assignee:
Chugai Seiyaku Kabushiki Kaisha
Inventors:
Tomoyuki Igawa, Shojiro Kadono, Naoka Hironiwa, Mika Sakurai
Abstract: In one aspect, disclosed herein is a method for evaluating the immunogenicity of a test substance in a short period of time by using, as an indicator of the immunogenicity of the test substance, the proportion of IL-2-secreting cells in a T cell population (preferably a CD4+ T cell population) at a time point during the early stage of IL-2 secretion after stimulation of the T cell population with the test substance (preferably 24 hours to 72 hours after the stimulation with the test substance).
Abstract: The present inventors found that peptide compounds/amide compounds in which the protecting groups of interest are removed and/or which are removed from resins for solid-phase synthesis can be produced without main chain damage by contacting starting peptide compounds/amide compounds with silylating agents.
Abstract: The present invention demonstrated that the modification of the Fc region of an antigen-binding molecule into an Fc region that does not form in a neutral pH range a heterotetramer complex containing two molecules of FcRn and an active Fc? receptor improved the pharmacokinetics of the antigen-binding molecule and reduced the immune response to the antigen-binding molecule. The present invention also revealed methods for producing antigen-binding molecules having the properties described above, and successfully demonstrated that pharmaceutical compositions containing as an active ingredient such an antigen-binding molecule or an antigen-binding molecule produced by a production method of the present invention have excellent features over conventional antigen-binding molecules in that when administered, they exhibit improved pharmacokinetics and reduced in vivo immune response.
Abstract: In one non-limiting embodiment, the present disclosure relates to lyophilized formulations containing an IL-31 antagonist (for example, an anti-IL-31RA antibody) as an active ingredient, the lyophilized formulations further containing arginine and/or a salt thereof and sucrose and/or trehalose. In another non-limiting embodiment, the present disclosure relates to solution formulations containing an IL-31 antagonist as an active ingredient, the solution formulations further containing arginine and/or a salt thereof.
Abstract: The present invention demonstrated that the modification of the Fc region of an antigen-binding molecule into an Fc region that does not form in a neutral pH range a heterotetramer complex containing two molecules of FcRn and an active Fc? receptor improved the pharmacokinetics of the antigen-binding molecule and reduced the immune response to the antigen-binding molecule. The present invention also revealed methods for producing antigen-binding molecules having the properties described above, and successfully demonstrated that pharmaceutical compositions containing as an active ingredient such an antigen-binding molecule or an antigen-binding molecule produced by a production method of the present invention have excellent features over conventional antigen-binding molecules in that when administered, they exhibit improved pharmacokinetics and reduced in vivo immune response.
Abstract: The present invention provides a filling nozzle obtained by using a resin selected from a cycloolefin polymer and a cycloolefin copolymer, or a filling nozzle including a tubular passage for supplying a pharmaceutical solution, and a filling port disposed at a lower end of the tubular passage, in which the tubular passage and the filling port have a circular peripheral cross-section, and an inner diameter of the passage of the filling port is larger than an inner diameter of the tubular passage disposed on an upstream side.
Abstract: The present invention provides efficient methods based on alteration of the protein A-binding ability, for producing or purifying multispecific antibodies having the activity of binding to two or more types of antigens to high purity through a protein A-based purification step alone. The methods of the present invention for producing or purifying multispecific antibodies which feature altering amino acid residues of antibody heavy chain constant region and/or variable region. Multispecific antibodies with an altered protein A-binding ability, which exhibit plasma retention comparable or longer than that of human IgG1, can be efficiently prepared in high purity by introducing amino acid alterations of the present invention into antibodies.
Type:
Application
Filed:
March 31, 2023
Publication date:
July 20, 2023
Applicant:
Chugai Seiyaku Kabushiki Kaisha
Inventors:
Tomoyuki Igawa, Zenjiro Sampei, Tetsuya Wakabayashi, Eriko Ito
Abstract: An objective of the present invention is to provide methods for facilitating antigen-binding molecule-mediated antigen uptake into cells, methods for facilitating the reduction of antigen concentration in plasma, methods for increasing the number of antigens to which a single antigen-binding molecule can bind, methods for improving pharmacokinetics of antigen-binding molecules, antigen-binding molecules improved for facilitated antigen uptake into cells, antigen-binding molecules capable of facilitating the reduction of antigen concentration in plasma, antigen-binding molecules capable of repeatedly binding to antigens, antigen-binding molecules with improved pharmacokinetics, pharmaceutical compositions comprising such an antigen-binding molecule, and methods for producing those described above.
Abstract: In one non-limiting embodiment, the present disclosure is an antibody-containing formulation comprising an anti-IL-6 receptor antibody as an active ingredient, and contains histidine-aspartate buffer or histidine-glutamate buffer, Poloxamer 188, and arginine, and has a pH of 5.5 to 6.6. In one non-limiting embodiment, the present disclosure is a method of stabilizing an antibody-containing solution, a method of suppressing antibody association (e.g., dimerization), and a method of suppressing the generation of insoluble particles, wherein L-aspartic acid or L-glutamic acid, and optionally, Poloxamer 188 are added.
Abstract: Various bispecific antibodies that specifically bind to both blood coagulation factor IX/activated blood coagulation factor IX and blood coagulation factor X and functionally substitute for the cofactor function of blood coagulation factor VIII, that is, the function to promote activation of blood coagulation factor X by activated blood coagulation factor IX, were produced. From these antibodies, multispecific antigen-binding molecules having a high activity of functionally substituting for blood coagulation factor VIII were successfully discovered.
Abstract: The present invention provides, in order to prepare matured hepatocytes analogous in various points to primary hepatocytes, a method for preparing hepatocytes or cells that can be differentiated into hepatocytes from pluripotent stem cells, comprising the steps of: (1) culturing the pluripotent stem cells in a medium containing an activator of an activin receptor-like kinase-4,7; (2) culturing the cells obtained in the step (1) in a medium containing a bone morphogenetic factor and a fibroblast growth factor; (3) culturing the cells obtained in the step (2) in a medium containing an activator of a hepatocyte growth factor receptor and an activator of an oncostatin M receptor; and (4) culturing the cells obtained in the step (3) to obtain hepatocytes or cells that can be differentiated into hepatocytes, wherein in at least one of the steps (2), (3) and (4), cells are cultured on a high-density collagen gel membrane.
Type:
Grant
Filed:
October 9, 2018
Date of Patent:
July 4, 2023
Assignees:
TOKYO INSTITUTE OF TECHNOLOGY, KANTO KAGAKU KABUSHIKI KAISHA, CHUGAI SEIYAKU KABUSHIKI KAISHA
Abstract: Postoperative adhesion formation at an invasion site and migration of neutrophils to the site of surgical invasion are suppressed by administering an anti-IL-6 receptor antibody and/or a neutrophil-neutralizing antibody.
Type:
Grant
Filed:
October 19, 2018
Date of Patent:
July 4, 2023
Assignees:
Hyogo College of Medicine, Chugai Seiyaku Kabushiki Kaisha
Abstract: Provided are a cancer therapeutic drug comprising a compound which inhibits GPX4 as an active ingredient, the cancer therapeutic drug treating cancer containing a cancer cell having a suppressed function of a SWI/SNF complex factor detected; and a method for predicting sensitivity of a cancer cell to a GPX4 inhibitor, the method comprising the step of predicting a cancer cell having a suppressed function of a SWI/SNF complex factor detected in the cancer cell, as having sensitivity to the GPX4 inhibitor.
Abstract: The present invention relates to granzyme B variants with increased protease activities and/or increased resistance against inhibitors; polynucleotides encoding the granzyme B variants; cells expressing the granzyme B variants; pharmaceutical compositions containing cells expressing the granzyme B variants; and pharmaceutical compositions containing the granzyme B variants. In some embodiments, the pharmaceutical compositions may be used in combination with cells expressing chimera receptors and/or antigen-binding molecules.
Abstract: The present inventors successfully obtained anti-NR10 antibodies having an effective neutralizing activity against NR10. The anti-NR10 antibodies provided by the present invention are useful as, for example, pharmaceuticals for treating or preventing inflammatory diseases.