Abstract: The disclosure provides anti-myostatin antibodies and methods of making and using the same. Nucleic acids encoding the anti-myostatin antibodies and host cells comprising the nucleic acids are also provided. The anti-myostatin antibodies have uses that include treating a muscle wasting disease, reducing body fat accumulation, and increasing mass and strength of muscle tissue. The disclosure also provides polypeptides containing a variant Fc region and methods of making and using the same. Nucleic acids encoding the polypeptides and host cells comprising the nucleic acids are also provided. The polypeptides have uses that include suppressing the activation of immune cells; treating an immunological inflammatory disease, autoimmune disease, or viral infection; and increasing muscle mass and strength or reducing body fat accumulation.
Abstract: Herein is reported a method for the production of an immunoglobulin comprising the following steps: a) providing a eukaryotic cell comprising a nucleic acid encoding the immunoglobulin, b) cultivating the eukaryotic cell in a cultivation medium wherein the amount of glucose available in the cultivation medium per time unit is kept constant and limited to less than 80% of the amount that could maximally be utilized by the cells in the cultivation medium per time unit, and c) recovering the immunoglobulin from the culture.
Abstract: The present application concerns methods for treating an IL-6-mediated disorder such as rheumatoid arthritis (RA), juvenile idiopathic arthritis (JIA), systemic JIA (sJIA), polyarticular course JIA (pcJIA), systemic sclerosis, or giant cell arteritis (GCA), with subcutaneously administered antibody that binds interleukin-6 receptor (anti-IL-6R antibody). In particular, it relates to identification of a fixed dose of anti-IL-6R antibody, e.g. tocilizumab, which is safe and effective for subcutaneous administration in patients with IL-6-mediated disorders. In addition, formulations and devices useful for subcutaneous administration of an anti-IL-6R antibody are disclosed.
Abstract: An improved solubility of a pharmaceutical composition or formulation containing a large amount of 9-ethyl-6,6-dimethyl-8-(4-morpholin-4-yl-piperidin-1-yl)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile or a salt thereof can be achieved by forming granules of the compound or salt thereof and allowing the granules to be present together with a disintegrating agent.
Abstract: The invention provides anti-myostatin antibodies and methods of using the same. In some embodiments, an isolated anti-myostatin antibody of the present invention binds to mature myostatin, and uptake of the antibody into cells is enhanced when complexed with the antigen. The invention also provides isolated nucleic acids encoding an anti-myostatin antibody of the present invention. The invention also provides host cells comprising a nucleic acid of the present invention. The invention also provides a method of producing an antibody comprising culturing a host cell of the present invention so that the antibody is produced. Anti-myostatin antibodies of the present invention may be for use as a medicament. Anti-myostatin antibodies of the present invention may be for use in treating a muscle wasting disease. Anti-myostatin antibodies of the present invention may be for use in increasing mass of muscle tissue.
Abstract: In the course of the present invention, it was discovered that one could regulate association between polypeptides by modifying amino acid residues that form the interface during the association to amino acids carrying the same type of charge. In this context, the present invention enables efficient formation of heterologous molecules. For example, the present invention can be suitably applied to the preparation of bispecific antibodies.
Abstract: Various bispecific antibodies that specifically bind to both blood coagulation factor DC/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 disclosure provides multispecific antigen-binding molecules that comprise a first antigen-binding moiety and a second antigen-binding moiety, each of which is capable of binding to CD3 and CD137, but does not bind to CD3 and CD137 at the same time; and a third antigen-binding moiety that is capable of binding to DLL3, preferably human DLL3, which induce T-cell dependent cytotoxity more efficiently whilst circumventing adverse toxicity concerns or side effects that other multispecific antigen-binding molecules may have. The present invention provides multispecific antigen-binding molecules and pharmaceutical compositions that can treat various cancers, especially those associated with DLL3, by comprising the antigen-binding molecule as an active ingredient.
Type:
Application
Filed:
February 14, 2022
Publication date:
August 11, 2022
Applicant:
Chugai Seiyaku Kabushiki Kaisha
Inventors:
Sotaro Naoi, Shu Feng, Tomoyuki Igawa, Shu Wen Samantha Ho
Abstract: The present inventors succeeded in improving the antibody constant region to have increased stability under acid conditions, reduced heterogeneity originated from disulfide bonds in the hinge region, reduced heterogeneity originated from the H chain C terminus, and increased stability at high concentrations as well as in discovering novel constant region sequences having reduced Fc? receptor-binding, while minimizing the generation of novel T-cell epitope peptides. As a result, the present inventors successfully discovered antibody constant regions with improved physicochemical properties (stability and homogeneity), immunogenicity, safety, and pharmacokinetics.
Abstract: The present inventors have successfully prepared an antibody Fc region dimer that has binding activity against each of an antigen and Fc?R, but does not bind to the antigen and the Fc?R at the same time, and a polypeptide comprising the Fc region dimer. The present invention enables the preparation of a multispecific binding polypeptide capable of avoiding an adverse reaction that may be caused by its binding to an antigen and Fc?R at the same time. Thus, the present invention provides a polypeptide suitable as a drug.
Abstract: A multiple antigen-binding molecule fusion molecule containing a multiple antigen-binding molecule (?) having an immune cell antigen-binding region and a cancer antigen-binding region, a cancer tissue-specific protease-cleavable linker (?), and a masking molecule (?) containing a polypeptide having the amino acid sequence QDGNE (SEQ ID NO: 15), in which the multiple antigen-binding molecule (?) and the masking molecule (?) are linked via the cancer tissue-specific protease-cleavable linker (?).
Abstract: The present invention provides hyaluronic acid derivatives into which a certain cationic group and a certain hydrophobic group are introduced, the hyaluronic acid derivatives including one or more repeating units represented by the formula (Ia) and one or more repeating units represented by the formula (Ib).
Abstract: Provided are suppressors of reduction of the blood-brain barrier (BBB) function, suppressors of the disruption of the tight junctions of the blood-brain barrier, suppressors of infiltration of leucocytes into the CNS, suppressors of permeation of IgGs in a patient's blood into the CNS, and therapeutic agents for neuromyelitis optica spectrum disorder, neuro-Behcet disease, neurosarcoidosis, central nervous system lupus (neuropsychiatric lupus), autoimmune encephalitis, or Vogt-Koyanagi-Harada disease which suppress reduction of blood-brain barrier function and/or restore reduced function of the blood-brain barrier, which contain an antibody containing a heavy chain variable region containing CDR1 having the sequence of SEQ ID NO: 1, CDR2 having the sequence of SEQ ID NO: 2, and CDR3 having the sequence of SEQ ID NO: 3, and a light chain variable region containing CDR1 having the sequence of SEQ ID NO: 4, CDR2 having the sequence of SEQ ID NO: 5, and CDR3 having the sequence of SEQ ID NO: 6.
Abstract: The present inventors produced a variety of bispecific antibodies that specifically bind to both F. IX/F. IXa and F. X, and functionally substitute for F. VIIIa, i.e., have a cofactor function to promote F. X activation via F. IXa. Among these antibodies, the antibody A44/B26 reduced coagulation time by 50 seconds or more as compared to that observed when the antibody was not added. The present inventors produced a commonly shared L chain antibody from this antibody using L chains of A44, and showed that A44L can be used as commonly shared L chains, although the activity of the resulting antibody is reduced compared to the original antibody (A44HL-B26HL). Further, with appropriate CDR shuffling, the present inventors successfully produced highly active multispecific antibodies that functionally substitute for coagulation factor VIII.
Abstract: The present invention provides a method for determining the efficacy of a GPC3-targeting therapeutic agent for a liver cancer patient and a GPC3-targeting therapeutic agent or a preparation which is to be administered to a patient for whom it has been determined that the GPC3-targeting therapeutic agent is effective. The present invention provides, for example, a method for determining that a GPC3-targeting therapeutic agent is effective when the expression level of GPC3 per tumor cell is a predetermined value, and a GPC3-targeting therapeutic agent or a preparation which is to be administered to a patient for whom it has been determined that the GPC3-targeting therapeutic agent is effective.
Abstract: Herein is reported a method for the production of an immunoglobulin comprising the following steps: a) providing a eukaryotic cell comprising a nucleic acid encoding the immunoglobulin, b) cultivating the eukaryotic cell in a cultivation medium wherein the amount of glucose available in the cultivation medium per time unit is kept constant and limited to less than 80% of the amount that could maximally be utilized by the cells in the cultivation medium per time unit, and c) recovering the immunoglobulin from the culture.
Abstract: Therapeutic agents and treatment methods for urologic cancers, particularly urologic cancers with reduced lysine (K)-specific demethylase 6A (KDM6A) function, the agents and methods being characterized by suppressing both IL-6 activity and CCR2/CCL2 activity, are provided.
Type:
Application
Filed:
April 16, 2020
Publication date:
June 30, 2022
Applicants:
HIROSHIMA UNIVERSITY, TOKYO WOMEN'S MEDICAL UNIVERSITY, CHUGAI SEIYAKU KABUSHIKI KAISHA
Abstract: The present inventors discovered that antibodies having weaker antigen-binding activity at the early endosomal pH in comparison with that at the pH of plasma are capable of binding to multiple antigen molecules with a single antibody molecule, have long half-lives in plasma, and have improved durations of time in which they can bind to antigen.
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: Disclosed is a library consisting essentially of a plurality of antigen-binding molecules differing in sequence from each other, wherein an antigen-binding domain in each of the antigen-binding molecules comprises at least one amino acid residue that changes the antigen-binding activity of the antigen-binding molecule depending on ion concentration conditions. Also disclosed are a composition comprising a plurality of polynucleotide molecules each encoding the antigen-binding molecules, a composition comprising a plurality of vectors each comprising the polynucleotide molecules, a method for selecting the antigen-binding molecules, a method for isolating the polynucleotide molecules, a method for producing the antigen-binding molecules, and a pharmaceutical composition comprising any of the antigen-binding molecules.