WO2009084659A1 - 高濃度抗体含有溶液製剤 - Google Patents

高濃度抗体含有溶液製剤 Download PDF

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Publication number
WO2009084659A1
WO2009084659A1 PCT/JP2008/073798 JP2008073798W WO2009084659A1 WO 2009084659 A1 WO2009084659 A1 WO 2009084659A1 JP 2008073798 W JP2008073798 W JP 2008073798W WO 2009084659 A1 WO2009084659 A1 WO 2009084659A1
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Prior art keywords
antibody
solution preparation
arginine
preparation according
solution
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PCT/JP2008/073798
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English (en)
French (fr)
Japanese (ja)
Inventor
Toshiyuki Morichika
Daisuke Kameoka
Yoshimi Imaeda
Terutoshi Maeda
Oliver Boris Stauch
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F Hoffmann La Roche AG
Chugai Pharmaceutical Co Ltd
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F Hoffmann La Roche AG
Chugai Pharmaceutical Co Ltd
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Priority to NZ586378A priority Critical patent/NZ586378A/en
Priority to DK08866971.8T priority patent/DK2238985T4/da
Priority to US12/810,938 priority patent/US8568720B2/en
Priority to KR1020107016322A priority patent/KR101083616B1/ko
Priority to MX2010004399A priority patent/MX2010004399A/es
Priority to RU2010131179/15A priority patent/RU2497544C2/ru
Priority to EP08866971.8A priority patent/EP2238985B2/en
Priority to ES08866971T priority patent/ES2389881T5/es
Priority to PL08866971.8T priority patent/PL2238985T5/pl
Priority to CA2708627A priority patent/CA2708627C/en
Priority to SI200830806T priority patent/SI2238985T2/sl
Priority to JP2009548102A priority patent/JP4937358B2/ja
Priority to UAA201009396A priority patent/UA104134C2/ru
Priority to BRPI0818903A priority patent/BRPI0818903B8/pt
Priority to HRP20120903TT priority patent/HRP20120903T4/hr
Priority to CN200880119066.5A priority patent/CN101883588B/zh
Priority to AU2008344292A priority patent/AU2008344292B2/en
Application filed by F Hoffmann La Roche AG, Chugai Pharmaceutical Co Ltd filed Critical F Hoffmann La Roche AG
Publication of WO2009084659A1 publication Critical patent/WO2009084659A1/ja
Priority to IL206548A priority patent/IL206548A/en
Priority to MA32948A priority patent/MA31934B1/fr
Anticipated expiration legal-status Critical
Priority to US14/017,013 priority patent/US20140005367A1/en
Priority to IL238896A priority patent/IL238896A/en
Priority to US14/963,414 priority patent/US20160090419A1/en
Priority to US16/390,197 priority patent/US11008394B2/en
Priority to US17/242,199 priority patent/US11359026B2/en
Priority to US17/752,978 priority patent/US11584798B2/en
Priority to US18/162,368 priority patent/US11767363B2/en
Priority to US18/335,789 priority patent/US20230340134A1/en
Priority to US18/656,957 priority patent/US20240317869A1/en
Priority to US18/780,956 priority patent/US20240376219A1/en
Priority to US18/792,080 priority patent/US20240392017A1/en
Priority to US19/191,167 priority patent/US20250257144A1/en
Ceased legal-status Critical Current

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/2866—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against receptors for cytokines, lymphokines, interferons
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
    • A61K39/39533—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals
    • A61K39/3955—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals against proteinaceous materials, e.g. enzymes, hormones, lymphokines
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
    • A61K39/39591—Stabilisation, fragmentation
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/16—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing nitrogen, e.g. nitro-, nitroso-, azo-compounds, nitriles, cyanates
    • A61K47/18—Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
    • A61K47/183—Amino acids, e.g. glycine, EDTA or aspartame
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/20—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing sulfur, e.g. dimethyl sulfoxide [DMSO], docusate, sodium lauryl sulfate or aminosulfonic acids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K1/00—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length
    • C07K1/14—Extraction; Separation; Purification
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
    • C07K2317/24—Immunoglobulins specific features characterized by taxonomic origin containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
    • C07K2317/76—Antagonist effect on antigen, e.g. neutralization or inhibition of binding

Definitions

  • the present invention relates to an antibody-containing preparation, and particularly to a stable high concentration antibody-containing solution preparation.
  • a high concentration antibody-containing solution tends to form a solution with high viscosity due to the nature of the protein as a macromolecule and intermolecular interaction. Furthermore, when the protein is stored in a high-concentration solution, deterioration phenomena such as the formation of insoluble and / or soluble aggregates become a problem and must be prevented. In particular, antibody preparations tend to form aggregates during storage in a solution and easily form insoluble aggregates. Further, when the solution preparation is stored for a long period of time, there is a problem that the bioactivity of the antibody molecule is lost due to deamidation of asparagine and other amino acid residues.
  • An object of the present invention is to provide a high-concentration antibody-containing preparation suitable for subcutaneous administration, in which dimer formation and deamidation during long-term storage are suppressed.
  • the present inventors have found that a stable antibody-containing solution preparation with a high concentration can be obtained by adding arginine, which is an amino acid, or a salt thereof as a stabilizer.
  • arginine which is an amino acid, or a salt thereof as a stabilizer.
  • the present invention has been completed.
  • the present invention provides the following.
  • a stable antibody-containing solution preparation characterized by containing arginine and methionine.
  • (4) The solution preparation according to (1) to (3), wherein the concentration of the antibody is 50 mg / ml or more.
  • (11) The solution preparation according to (1) to (10), wherein the pH is 4 to 8.
  • (12) The solution preparation according to (1) to (11), wherein the content of arginine is 50 to 1500 mM.
  • a high-concentration antibody-containing preparation that does not require reconstitution by freeze-drying and does not require re-dissolution. Since the high-concentration antibody-containing preparation of the present invention can be stably stored for a long time in a solution state and can be produced without including a freeze-drying step in the production process, it is not necessary to add sugar or the like as a cryoprotectant. .
  • Example 2 is a typical chromatograph of Example 1.
  • the evaluation result of the gel filtration chromatograph method (SEC) of Example 1 is shown.
  • the evaluation result of the gel filtration chromatograph method (SEC) of Example 1 is shown.
  • 2 is a typical chromatograph of Example 2.
  • the evaluation result of the ion exchange chromatography method (IEC) of Example 2 is shown.
  • the evaluation result of the ion exchange chromatography method (IEC) of Example 2 is shown.
  • the evaluation result of the gel filtration chromatograph method (SEC) of Example 3 is shown.
  • the evaluation result of the ion exchange chromatography method (IEC) of Example 3 is shown.
  • the antibody-containing solution preparation refers to a solution preparation prepared so that it contains an antibody as an active ingredient and can be administered to an animal such as a human, and is preferably manufactured without including a freeze-drying step in the manufacturing process.
  • solution formulation refers to solution formulation.
  • the antibody-containing solution preparation of the present invention is a solution preparation containing a high concentration of antibody, preferably having an antibody concentration of 50 mg / mL or more, more preferably 100 mg / mL or more, and 120 mg / mL or more. Is more preferable, and 150 mg / mL is more preferable.
  • an antibody-containing solution preparation of 120 mg / mL or more, preferably 150 mg / mL or more there has been no practical use of an antibody-containing solution preparation of 120 mg / mL or more, preferably 150 mg / mL or more, and the high-concentration antibody-containing solution preparation can be put into practical use for the first time by the formulation of the present invention. It became.
  • the upper limit of the antibody concentration of the antibody-containing solution preparation of the present invention is generally 300 mg / mL, preferably 250 mg / mL, more preferably 200 mg / mL from the viewpoint of production. Therefore, the antibody concentration of the high concentration antibody solution preparation of the present invention is preferably 50 to 300 mg / mL, more preferably 100 to 300 mg / mL, further preferably 120 to 250 mg / mL, and particularly preferably 150 to 200 mg / mL.
  • the antibody used in the present invention is not particularly limited as long as it binds to a desired antigen, and may be a polyclonal antibody or a monoclonal antibody, but a monoclonal antibody is preferable in that a homogeneous antibody can be stably produced. .
  • the monoclonal antibodies used in the present invention include not only monoclonal antibodies derived from animals such as humans, mice, rats, hamsters, rabbits, sheep, camels, monkeys, but also artificial antibodies such as chimeric antibodies, humanized antibodies, and bispecific antibodies. Modified genetically modified antibodies are also included.
  • the immunoglobulin class of the antibody is not particularly limited, and may be any class such as IgG such as IgG1, IgG2, IgG3, and IgG4, IgA, IgD, IgE, and IgM, and IgG and IgM are preferable.
  • the antibodies of the present invention are not only whole antibodies, but also antibody fragments such as Fv, Fab, F (ab) 2 and the like, and monovalent or bivalent or more obtained by binding antibody variable regions with a linker such as a peptide linker.
  • Low molecular weight antibodies such as single chain Fv (Diabody such as scFv, sc (Fv) 2 and scFv dimer) are also included.
  • a hybridoma producing a monoclonal antibody can be basically produced using a known technique as follows. That is, a desired antigen or a cell expressing the desired antigen is used as a sensitizing antigen and immunized according to a normal immunization method, and the resulting immune cell is fused with a known parent cell by a normal cell fusion method. And can be prepared by screening monoclonal antibody-producing cells (hybridomas) by a normal screening method.
  • the hybridoma can be prepared, for example, according to the method of Milstein et al. (Kohler. G. and Milstein, C., Methods Enzymol. (1981) 73: 3-46). When the immunogenicity of the antigen is low, immunization may be performed by binding to an immunogenic macromolecule such as albumin.
  • a recombinant antibody produced by cloning an antibody gene from a hybridoma, incorporating it into a suitable vector, introducing it into a host, and using a gene recombination technique can be used (for example, Carl, A). K. Borrebaeck, James, W. Larrick, THERAPEUTIC MONOCLONAL ANTIBODIES, Published in the United Kingdom by MACMILLAN PUBLISHERS LTD, 1990).
  • cDNA of the variable region (V region) of the antibody is synthesized from the hybridoma mRNA using reverse transcriptase.
  • DNA encoding the V region of the antibody may be incorporated into an expression vector containing the DNA ⁇ of the antibody C region. It is incorporated into an expression vector so as to be expressed under the control of an expression control region such as an enhancer or promoter.
  • host cells can be transformed with this expression vector to express the antibody.
  • a recombinant antibody that has been artificially modified for the purpose of reducing the heteroantigenicity to humans such as a chimeric antibody or a humanized antibody
  • modified antibodies can be produced using known methods.
  • a chimeric antibody is a mammal other than a human, for example, a mouse antibody heavy chain, light chain variable region and a human antibody heavy chain, light chain constant region, and a DNA encoding the murine antibody variable region.
  • a humanized antibody also called a reshaped human antibody, is a non-human mammal, such as a mouse antibody complementarity-determining region (CDR) grafted to the complementarity-determining region of a human antibody.
  • CDR complementarity-determining region
  • EP 239400 International Patent Application Publication No. (See WO 96/962).
  • a complementarity determining region that forms a favorable antigen binding site is selected. If necessary, the amino acid in the framework region of the variable region of the antibody may be substituted so that the complementarity determining region of the reshaped human antibody forms an appropriate antigen-binding site (Sato, K.et al., Cancer Res. (1993) 53, 851-856).
  • a method for obtaining a human antibody is also known.
  • human lymphocytes are sensitized with a desired antigen or cells expressing the desired antigen in vitro, and the sensitized lymphocytes are fused with human myeloma cells, such as U266, to have a desired human antibody having an antigen-binding activity.
  • a desired human antibody can be obtained by immunizing a transgenic animal having all repertoires of human antibody genes with an antigen (International Patent Application Publication Nos. WO 93/12227, WO 92/03918, WO 94 / 02602, WO 94/25585, WO 96/34096,) WO 96/33735).
  • variable region of a human antibody is expressed as a single chain antibody (scFv) on the surface of the phage by the phage display method, and a phage that binds to the antigen can be selected.
  • scFv single chain antibody
  • the DNA sequence encoding the variable region of the human antibody that binds to the antigen can be determined. If the DNA sequence of scFv that binds to the antigen is clarified, a suitable expression vector containing the sequence can be prepared and a human antibody can be obtained.
  • an antibody gene When an antibody gene is once isolated and introduced into an appropriate host to produce an antibody, a combination of an appropriate host and an expression vector can be used.
  • animal cells When eukaryotic cells are used as hosts, animal cells, plant cells, and fungal cells can be used.
  • Animal cells include (1) mammalian cells such as CHO, COS, myeloma, BHK (baby hamster kidney ,), HeLa, Vero, (2) amphibian cells, such as Xenopus oocytes, or (3) insect cells.
  • mammalian cells such as CHO, COS, myeloma, BHK (baby hamster kidney ,), HeLa, Vero
  • amphibian cells such as Xenopus oocytes
  • insect cells For example, sf9, sf21, Tn5, etc. are known.
  • Nicotiana for example, Nicotiana tabacum
  • these may be cultured in callus.
  • Known fungal cells include yeasts such as the genus Saccharomyces, such as Saccharomyces cerevisiae, and filamentous fungi such as the genus Aspergillus, such as Aspergillus niger. When prokaryotic cells are used, there are production systems using bacterial cells.
  • Known bacterial cells include E. coli (E.Ecoli) and Bacillus subtilis.
  • An antibody can be obtained by introducing a desired antibody gene into these cells by transformation, and culturing the transformed cells in vitro.
  • the antibody of the present invention may be an antibody fragment thereof, a low molecular weight antibody, or an antibody modification product.
  • Fab, F (ab ′) 2, Fv, or a mono-chain or bivalent or more single chain Fv (scFv, Fv of H chain and L chain linked by an appropriate linker) sc (Fv) 2 etc.) Huston, J. S. et al., Proc. Natl. Acad. Sci. USA (1988) 85, 5879-5883.
  • the antibody is treated with an enzyme such as papain or pepsin to generate antibody fragments, or a gene encoding these antibody fragments is constructed and introduced into an expression vector, and then an appropriate host cell.
  • an enzyme such as papain or pepsin to generate antibody fragments, or a gene encoding these antibody fragments is constructed and introduced into an expression vector, and then an appropriate host cell.
  • an antibody conjugated with various molecules such as polyethylene glycol (PEG) can also be used.
  • PEG polyethylene glycol
  • the “antibody” of the present invention includes these modified antibodies. In order to obtain such a modified antibody, it can be obtained by chemically modifying the obtained antibody. These methods are already established in this field.
  • Examples of the antibody contained in the preparation of the present invention include anti-tissue factor antibody, anti-IL-6 receptor antibody, anti-IL-6 antibody, HM1.24 antigen monoclonal antibody, anti-parathyroid hormone related peptide antibody (anti-PTHrP antibody), Anti-ganglioside GM3 antibody, anti-TPO receptor agonist antibody, coagulation factor VIII substitute antibody, anti-CD3 antibody, anti-CD20 antibody, anti-GPIIb / IIIa antibody, anti-TNF antibody, anti-CD25 antibody, anti-EGFR antibody, Examples include, but are not limited to, anti-Her2 / neu antibody, anti-RSV antibody, anti-CD33 antibody, anti-CD52 antibody, anti-IgE antibody, anti-CD11a antibody, anti-VEGF antibody, anti-VLA4 antibody, and anti-AXL antibody.
  • Reshaped humanized antibodies include humanized anti-interleukin 6 (IL-6) receptor antibody (hPM-1 or MRA) (see International Patent Application Publication No. WO92-19759), humanized anti-HM1.24 antigen monoclonal antibody (See International Patent Application Publication Number WO 98-14580), Humanized Anti-parathyroid Hormone Related Peptide Antibody (Anti-PTHrP Antibody) (See International Patent Application Publication Number WO 98-13388), Humanized Anti-Tissue Factor Antibody (International Patent Application) Publication number WO99-51743), anti-glypican-3 humanized IgG1 ⁇ antibody (see International Patent Application No. PCT / JP05 / 013103) and the like are preferred antibodies for use in the present invention. Particularly preferred as a humanized antibody for use in the present invention is a humanized anti-IL-6 receptor antibody.
  • anti-ganglioside GM3 recombinant human IgM antibody As the human IgM antibody, anti-ganglioside GM3 recombinant human IgM antibody (see International Patent Application Publication No. WO05-05636) is preferable.
  • an anti-TPO receptor agonist Diabody see International Patent Application Publication No. WO02-33072
  • an anti-CD47 agonist Diabody see International Patent Application Publication No. WO01-66737
  • the like are preferable.
  • the present inventors examined the effects of various additives by a thermal acceleration test and a light acceleration test in order to evaluate the stability of a high-concentration antibody-containing sample during storage.
  • a solution in which a high-concentration antibody is dissolved in a buffer solution containing the amino acid arginine has a lower dimer production amount than a solution without arginine added, and therefore suppresses dimer production. It has been found that arginine is effective as a stabilizer.
  • the first aspect of the present invention is characterized by adding arginine to a solution, thereby inhibiting dimerization or deamidation of antibody molecules in an antibody-containing solution formulation.
  • the aspect as a stable antibody-containing solution formulation is characterized by containing an antibody and arginine in a buffer solution.
  • the antibody-containing solution preparation of the present invention further exhibits a synergistic effect due to the combined use of arginine and methionine by containing methionine.
  • the second aspect of the present invention is characterized by adding arginine and methionine to the solution, and particularly relates to suppressing antibody dimer formation in an antibody-containing solution preparation.
  • the aspect as a stable antibody containing solution formulation is characterized by containing an antibody, arginine, and methionine in a buffer solution.
  • arginine used in the present invention either a single product, a derivative thereof, or a salt thereof may be used, and L-arginine or a salt thereof is particularly desirable.
  • methionine used in the present invention either a single product, a derivative thereof, or a salt thereof may be used, and L-methionine or a salt thereof is particularly desirable.
  • the amount of arginine is preferably 50 to 1500 mM, more preferably 100 to 1000 mM, and 200 to 700 mM. More preferably.
  • the total concentration of arginine and methionine is 50 to 1200 mM, for example, the amount of arginine is 40 to 1000 mM and the amount of methionine is 10 to 200 mM.
  • the amount of arginine is 50 to 700 mM and the amount of methionine is 10 to 100 mM, the amount of arginine is 100 to 300 mM, and the amount of methionine is 10 to 50 mM. Is more preferable.
  • the buffer solution is prepared using a buffering agent that is a substance for maintaining the pH of the solution.
  • the pH of the solution is preferably 4 to 8, more preferably 5.0 to 7.5, and more preferably 5.5 to 7.2. More preferably, it is more preferably 6.0 to 6.5.
  • the buffering agent that can be used in the present invention can adjust the pH within this range and is pharmaceutically acceptable.
  • buffers are known to those skilled in the art of solution formulation and include, for example, inorganic salts such as phosphate (sodium or potassium), sodium bicarbonate; citrate (sodium or potassium), sodium acetate, succinate Organic acid salts such as sodium acid; or acids such as phosphoric acid, carbonic acid, citric acid, succinic acid, malic acid, gluconic acid can be used.
  • Tris and Good buffers such as MES, MOPS, and HEPES, histidine (for example, histidine hydrochloride), glycine, and the like may be used.
  • the buffer is preferably a histidine buffer or a glycine buffer, and particularly preferably a histidine buffer.
  • concentration of the buffer is generally 1 to 500 mM, preferably 5 to 100 mM, and more preferably 10 to 20 mM.
  • the buffer preferably contains 5-25 mM histidine, more preferably 10-20 mM histidine.
  • the “stable” high concentration antibody-containing solution formulation of the present invention has a refrigeration temperature (2-8 ° C.) for at least 12 months, preferably 2 years, more preferably 3 years; or at room temperature (22-28 ° C.) at least 3 No significant changes are observed for months, preferably 6 months, more preferably 1 year.
  • the total amount of dimer and degradation products after storage at 5 ° C. for 2 years is 5.0% or less, preferably 2% or less, more preferably 1.5% or less, or after storage at 25 ° C. for 6 months.
  • the total amount of dimer and decomposed product is 5.0% or less, preferably 2% or less, more preferably 1.5% or less.
  • the preparation of the present invention can further contain a surfactant.
  • Surfactants include nonionic surfactants such as sorbitan fatty acid esters such as sorbitan monocaprylate, sorbitan monolaurate, and sorbitan monopalmitate; glycerin such as glycerin monocaprylate, glycerin monomylate, and glycerin monostearate.
  • nonionic surfactants such as sorbitan fatty acid esters such as sorbitan monocaprylate, sorbitan monolaurate, and sorbitan monopalmitate
  • glycerin such as glycerin monocaprylate, glycerin monomylate, and glycerin monostearate.
  • Fatty acid ester Fatty acid ester; polyglycerin fatty acid ester such as decaglyceryl monostearate, decaglyceryl distearate, decaglyceryl monolinoleate; polyoxyethylene sorbitan monolaurate, polyoxyethylene sorbitan monooleate, polyoxyethylene sorbitan monostearate Polyoxyethylene sorbitan monopalmitate, polyoxyethylene sorbitan trioleate, polyoxyethylene sorbitan tristearate, etc.
  • polyglycerin fatty acid ester such as decaglyceryl monostearate, decaglyceryl distearate, decaglyceryl monolinoleate
  • polyoxyethylene sorbitan monolaurate polyoxyethylene sorbitan monooleate
  • polyoxyethylene sorbitan monostearate Polyoxyethylene sorbitan monopalmitate, polyoxyethylene sorbitan trioleate, polyoxyethylene sorbitan tristearate, etc.
  • polyoxyethylene sorbitan fatty acid ester such as polyoxyethylene sorbite tetrastearate and polyoxyethylene sorbite tetraoleate
  • polyoxyethylene glycerin fatty acid ester such as polyoxyethylene glyceryl monostearate
  • polyethylene glycol distea Polyethylene glycol fatty acid esters such as rate
  • polyoxyethylene alkyl ethers such as polyoxyethylene lauryl ether
  • polyoxyethylene Polyoxyethylene alkyl phenyl ethers such as nonylphenyl ether
  • polyoxyethylene hydrogenated castor oil such as polyoxyethylene castor oil, polyoxyethylene hydrogenated castor oil (polyoxyethylene hydrogen castor oil); polyoxyethylene sorbite bee
  • Preferred surfactants are polyoxyethylene sorbitan fatty acid esters and polyoxyethylene polyoxypropylene alkyl ethers, particularly preferred are polysorbates 20, 21, 40, 60, 65, 80, 81, 85 and pluronic surfactants. And most preferred are polysorbates 20, 80 and Pluronic F-68 (poloxamer 188).
  • the amount of the surfactant added to the antibody preparation of the present invention is generally 0.0001 to 10% (w / v), preferably 0.001 to 5%, more preferably 0.005 to 3%.
  • the formulation of the present invention preferably comprises the following components: A) Anti-IL-6 receptor antibody B) Arginine and / or methionine, and additional amino acids as optional additional components (eg tryptophan) It consists essentially of C) a buffer and D) a surfactant.
  • “Substantially composed” means a suspending agent, a solubilizing agent, an isotonic agent, a preservative, an adsorption inhibitor, a diluent, an excipient, a pH adjuster, which are optional additives described later. This means that it contains no components other than those added to normal preparations such as soothing agents, sulfur-containing reducing agents, and antioxidants.
  • arginine and / or methionine, and further additional amino acid as an optional additional component means that the type of amino acid as an additive that can be contained in the preparation is (b-1) arginine (B-2) arginine and methionine; (b-3) methionine, which means that further amino acids may be included.
  • a preferred example is tryptophan.
  • tryptophan either a single product, a derivative thereof or a salt thereof may be used, and L-tryptophan or a salt thereof is particularly desirable.
  • a suspending agent a solubilizer, an isotonic agent, a preservative, an adsorption inhibitor, a diluent, an excipient, a pH adjuster, a soothing agent, a sulfur-containing reduction agent.
  • An agent, an antioxidant and the like can be added as appropriate.
  • suspending agent examples include methyl cellulose, polysorbate 80, hydroxyethyl cellulose, gum arabic, tragacanth powder, sodium carboxymethyl cellulose, polyoxyethylene sorbitan monolaurate and the like.
  • solution auxiliary examples include polyoxyethylene hydrogenated castor oil, polysorbate 80, nicotinic acid amide, polyoxyethylene sorbitan monolaurate, Magrogol, castor oil fatty acid ethyl ester, and the like.
  • isotonic agents examples include sodium chloride, potassium chloride, calcium chloride and the like.
  • preservative examples include methyl paraoxybenzoate, ethyl paraoxybenzoate, sorbic acid, phenol, cresol, chlorocresol and the like.
  • adsorption inhibitor examples include human serum albumin, lecithin, dextran, ethylene oxide / propylene oxide copolymer, hydroxypropyl cellulose, methyl cellulose, polyoxyethylene hydrogenated castor oil, polyethylene glycol and the like.
  • sulfur-containing reducing agent examples include N-acetylcysteine, N-acetylhomocysteine, thioctic acid, thiodiglycol, thioethanolamine, thioglycerol, thiosorbitol, thioglycolic acid and salts thereof, sodium thiosulfate, glutathione, carbon Examples thereof include those having a sulfhydryl group such as thioalkanoic acid having 1 to 7 atoms.
  • antioxidants examples include erythorbic acid, dibutylhydroxytoluene, butylhydroxyanisole, ⁇ -tocopherol, tocopherol acetate, L-ascorbic acid and its salt, L-ascorbyl palmitate, L-ascorbic acid stearate, sodium bisulfite, Chelating agents such as sodium sulfite, triamyl gallate, propyl gallate or disodium ethylenediaminetetraacetate (EDTA), sodium pyrophosphate, sodium metaphosphate and the like can be mentioned.
  • EDTA disodium ethylenediaminetetraacetate
  • the antibody-containing solution preparation of the present invention is usually administered by a parenteral administration route such as injection (subcutaneous injection, intravenous injection, intramuscular injection, etc.), transdermal, transmucosal, nasal, transpulmonary, etc. Is also possible.
  • parenteral administration route such as injection (subcutaneous injection, intravenous injection, intramuscular injection, etc.), transdermal, transmucosal, nasal, transpulmonary, etc. Is also possible.
  • the dosage per antibody is large (about 100 to 200 mg-), but the amount of injection solution is limited. Therefore, the preparation of the present invention is particularly suitable for subcutaneous injection.
  • the osmotic pressure ratio of the antibody-containing solution preparation of the present invention is about 0.5 to 4, more preferably about 0.7 to 2, and still more preferably about 1.
  • the antibody-containing solution preparation of the present invention has a viscosity of about 2 to 15 mPa ⁇ s, more preferably about 4 to 10 mPa ⁇ s.
  • the viscosity of the present invention is measured by a rotational viscometer method using a cone plate viscometer (15th revision, Japanese Pharmacopoeia, General Test Method 2.53 Viscosity Measurement Method).
  • a method for suppressing deamidation of an antibody-containing solution preparation which comprises adding arginine or a salt thereof to a solution.
  • a method for suppressing antibody dimer formation in an antibody-containing solution preparation which comprises adding arginine and methionine to the solution.
  • the antibody is preferably an anti-interleukin-6 receptor antibody which is a humanized antibody or a human antibody.
  • Antibody sample Anti-IL-6 receptor humanized antibody utilizes the human elongation factor I ⁇ promoter described in Example 10 of International Patent Application Publication No. WO92 / 197559, and Reference Example 2 of JP-A-8-99902.
  • a humanized antibody prepared according to the method described in 1. above. In the table of Examples, it may be described as MRA.
  • sample Nos. A1 to A9 were prepared.
  • the prescription of each evaluation sample is as follows.
  • each sample was subjected to a thermal acceleration test (40 ° C-3 months and 25 ° C-6 months storage). Then, the purity of the antibody before and after thermal acceleration was evaluated by gel filtration chromatography (SEC). The analysis conditions are as follows. [Gel filtration chromatography] Use the sample as the measurement solution.
  • FIG. 1 A typical chromatograph is shown in FIG. 1
  • sample Nos. A10 to A15 and sample Nos. A16 to A18 having different addition amounts of arginine and methionine were prepared.
  • the prescription of each evaluation sample is as follows.
  • each sample was subjected to a thermal acceleration test (40 ° C-3 months and 25 ° C-6 months storage). Then, the purity of the antibody before and after thermal acceleration was evaluated by ion exchange chromatography (IEC).
  • IEC ion exchange chromatography
  • the analysis conditions are as follows. [Ion exchange chromatography] Purified water is added to the sample, and a solution containing about 1 mg of anti-IL-6 receptor humanized antibody in 1 mL is prepared as the measurement solution for each sample.
  • MRA-Pre is the sum of peaks eluted with a shorter retention time than the main component, and contains multiple degradation products centered on deamidated anti-IL-6 receptor humanized antibodies. A small amount of this Pre peak generated means that deamidation of this antibody is suppressed.
  • MRA Pre is the sum of all peaks that appear before MRA Main.
  • the evaluation results of the ion exchange chromatography method (IEC) according to this example are shown in Table 2, FIG. 5, and FIG.
  • the samples with arginine added (Sample Nos. A11 to A15) were accelerated by 40 ° C for 3 months and 25 ° C for 6 months, and the pre peak amount was not added to the sample without arginine (Sample No. A10).
  • the inhibitory effect of pre-peak generation by arginine was confirmed. It was also confirmed that the Pre peak amount decreased in proportion to the amount of arginine added.
  • the pre-peak amount due to acceleration for 40 ° C-3 months and 25 ° C-6 months is the same as the sample without arginine (sample No. A10) Thus, no effect of methionine addition was observed.
  • sample Nos. A19 to A27 were prepared.
  • the prescription of each evaluation sample is as follows.
  • each sample was subjected to a light acceleration test (total illumination of 1.2 million lux and total near-ultraviolet irradiation energy of 200 W ⁇ h / m 2 ). And the purity of the antibody before and behind light acceleration was evaluated by the same gel filtration chromatography method (SEC) and ion exchange chromatography method (IEC) as in Examples 1 and 2.
  • SEC gel filtration chromatography method
  • IEC ion exchange chromatography method
  • the sample with arginine (Sample No. A20 to A24) has a lower pre-peak amount due to light acceleration than the sample without arginine (Sample No. A19), and suppresses the production of Pre peak by arginine. I was able to confirm. It was also confirmed that the amount of pre-peak decreased in proportion to the amount of arginine added.
  • the sample with methionine added to arginine 100 ⁇ ⁇ mM
  • the dimer amount by photoacceleration is almost the same as the total stabilizer concentration, and the sample with an arginine concentration of 150 mM ( It was lower than Sample No.

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US12/810,938 US8568720B2 (en) 2007-12-27 2008-12-26 High concentration antibody-containing liquid formulation
SI200830806T SI2238985T2 (sl) 2007-12-27 2008-12-26 Tekoča formulacija z visoko koncentracijo protitelesa
MX2010004399A MX2010004399A (es) 2007-12-27 2008-12-26 Formulacion liquida que contiene anticuerpos en una alta concentracion.
RU2010131179/15A RU2497544C2 (ru) 2007-12-27 2008-12-26 Жидкая композиция, содержащая антитело высокой концентрации
EP08866971.8A EP2238985B2 (en) 2007-12-27 2008-12-26 High concentration antibody-containing liquid formulation
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NZ586378A NZ586378A (en) 2007-12-27 2008-12-26 Solution preparation containing antibody at high concentration
DK08866971.8T DK2238985T4 (da) 2007-12-27 2008-12-26 Højkoncentreret antistofholdig væskeformulering
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BRPI0818903A BRPI0818903B8 (pt) 2007-12-27 2008-12-26 formulação líquida contendo anticorpo de concentração elevada e métodos para inibir a desamidação e dimerização de moléculas de um anticorpo em uma formulação líquida contendo o anticorpo
HRP20120903TT HRP20120903T4 (hr) 2007-12-27 2008-12-26 Tekuća formulacija koja sadrži visoku koncentraciju protutijela
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MA32948A MA31934B1 (fr) 2007-12-27 2010-06-25 Formulation liquide contenant un anticorps a forte concentration
US14/017,013 US20140005367A1 (en) 2007-12-26 2013-09-03 High concentration antibody-containing liquid formulation
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Cited By (53)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2011084750A1 (en) * 2009-12-21 2011-07-14 Genentech, Inc. Antibody formulation
JP2012072170A (ja) * 2007-12-27 2012-04-12 Chugai Pharmaceut Co Ltd 高濃度抗体含有溶液製剤
WO2013012022A1 (ja) 2011-07-19 2013-01-24 中外製薬株式会社 アルギニンアミドまたはその類似化合物を含む安定なタンパク質含有製剤
WO2013031237A1 (en) 2011-09-01 2013-03-07 Chugai Seiyaku Kabushiki Kaisha Method for preparing a composition comprising highly concentrated antibodies by ultrafiltration
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US8840884B2 (en) 2002-02-14 2014-09-23 Chugai Seiyaku Kabushiki Kaisha Antibody-containing solution pharmaceuticals
JP2015527402A (ja) * 2012-09-07 2015-09-17 コヒラス・バイオサイエンシズ・インコーポレイテッド 安定水性アダリムマブ製剤
AU2013202276B2 (en) * 2009-12-21 2016-03-24 Genentech, Inc. Antibody formulation
JPWO2014010586A1 (ja) * 2012-07-10 2016-06-23 武田薬品工業株式会社 注射用製剤
WO2017057644A1 (ja) * 2015-09-30 2017-04-06 持田製薬株式会社 高濃度抗体含有液体製剤
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WO2017188356A1 (ja) * 2016-04-28 2017-11-02 中外製薬株式会社 抗体含有製剤
WO2018060210A1 (en) 2016-09-27 2018-04-05 Ares Trading S.A. Liquid pharmaceutical composition
WO2018078162A1 (en) 2016-10-31 2018-05-03 Ares Trading S.A. Liquid pharmaceutical composition
WO2018179138A1 (ja) * 2017-03-29 2018-10-04 持田製薬株式会社 抗体含有液体製剤
US10168326B2 (en) 2013-07-04 2019-01-01 F. Hoffmann-La Roche Inc. Interference-suppressed immunoassay to detect anti-drug antibodies in serum samples
US10450381B2 (en) 2010-11-17 2019-10-22 Chugai Seiyaku Kabushiki Kaisha Methods of treatment that include the administration of bispecific antibodies
US10501769B2 (en) 2009-10-26 2019-12-10 Hoffmann-La Roche Inc. Method for the production of a glycosylated immunoglobulin
WO2020056008A1 (en) 2018-09-12 2020-03-19 Silverback Therapeutics, Inc. Compositions for the treatment of disease with immune stimulatory conjugates
JP2020114819A (ja) * 2014-05-16 2020-07-30 グラクソスミスクライン、インテレクチュアル、プロパティー、マネジメント、リミテッドＧｌａｘｏｓｍｉｔｈｋｌｉｎｅ Ｉｎｔｅｌｌｅｃｔｕａｌ Ｐｒｏｐｅｒｔｙ Ｍａｎａｇｅｍｅｎｔ Ｌｉｍｉｔｅｄ 抗体処方物
US10759870B2 (en) 2017-09-29 2020-09-01 Chugai Seiyaku Kabushiki Kaisha Multispecific antigen-binding molecules having blood coagulation factor VIII (FVIII) cofactor function-substituting activity and pharmaceutical formulations containing such a molecule as an active ingredient
WO2020185750A1 (en) * 2019-03-11 2020-09-17 Biogen Ma Inc. Pharmaceutical compositions containing anti-lingo-1 antibodies
WO2020257407A1 (en) 2019-06-19 2020-12-24 Silverback Therapeutics, Inc. Anti-mesothelin antibodies and immunoconjugates thereof
US10934344B2 (en) 2006-03-31 2021-03-02 Chugai Seiyaku Kabushiki Kaisha Methods of modifying antibodies for purification of bispecific antibodies
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US11046784B2 (en) 2006-03-31 2021-06-29 Chugai Seiyaku Kabushiki Kaisha Methods for controlling blood pharmacokinetics of antibodies
US11071782B2 (en) 2016-04-20 2021-07-27 Coherus Biosciences, Inc. Method of filling a container with no headspace
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US11179473B2 (en) 2020-02-21 2021-11-23 Silverback Therapeutics, Inc. Nectin-4 antibody conjugates and uses thereof
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US11229702B1 (en) 2015-10-28 2022-01-25 Coherus Biosciences, Inc. High concentration formulations of adalimumab
US11248053B2 (en) 2007-09-26 2022-02-15 Chugai Seiyaku Kabushiki Kaisha Method of modifying isoelectric point of antibody via amino acid substitution in CDR
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US11541126B1 (en) 2020-07-01 2023-01-03 Silverback Therapeutics, Inc. Anti-ASGR1 antibody TLR8 agonist comprising conjugates and uses thereof
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US11801300B2 (en) 2014-12-22 2023-10-31 Novartis Ag Pharmaceutical products and stable liquid compositions of IL-17 antibodies
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JO3672B1 (ar) 2008-12-15 2020-08-27 Regeneron Pharma أجسام مضادة بشرية عالية التفاعل الكيماوي بالنسبة لإنزيم سبتيليسين كنفرتيز بروبروتين / كيكسين نوع 9 (pcsk9).
US9345661B2 (en) 2009-07-31 2016-05-24 Genentech, Inc. Subcutaneous anti-HER2 antibody formulations and uses thereof
AR078161A1 (es) 2009-09-11 2011-10-19 Hoffmann La Roche Formulaciones farmaceuticas muy concentradas de un anticuerpo anti cd20. uso de la formulacion. metodo de tratamiento.
JO3417B1 (ar) 2010-01-08 2019-10-20 Regeneron Pharma الصيغ المستقرة التي تحتوي على الأجسام المضادة لمضاد مستقبل( interleukin-6 (il-6r
BR112013008366B1 (pt) * 2010-10-06 2022-02-08 Regeneron Pharmaceuticals, Inc Formulações farmacêuticas líquidas estáveis contendo anticorpos anti-receptor de interleucina-4 humana alfa, e recipiente contendo as referidas formulações
PL3395836T3 (pl) 2011-01-28 2021-12-13 Sanofi Biotechnology Ludzkie przeciwciała przeciwko pcsk9 do zastosowania w sposobach leczenia konkretnych grup osobników
EP2508525A1 (en) 2011-04-05 2012-10-10 Bayer Pharma Aktiengesellschaft Substituted 2,3-dihydroimidazo[1,2-c]quinazoline salts
CA2832560A1 (en) * 2011-04-07 2012-10-18 Glaxosmithkline Llc Formulations with reduced viscosity
UY34105A (es) * 2011-06-03 2012-07-31 Lg Life Sciences Ltd Formulación líquida estable de etanercept
AR087305A1 (es) 2011-07-28 2014-03-12 Regeneron Pharma Formulaciones estabilizadas que contienen anticuerpos anti-pcsk9, metodo de preparacion y kit
SG10201604104PA (en) 2011-10-25 2016-07-28 Prothena Therapeutics Ltd Antibody formulations and methods
AU2012328524B2 (en) 2011-10-28 2017-05-18 Excelse Bio, Inc. Protein formulations containing amino acids
WO2013164837A1 (en) 2012-03-07 2013-11-07 Cadila Healthcare Limited Pharmaceutical formulations of tnf-alpha antibodies
US9969794B2 (en) 2012-05-10 2018-05-15 Visterra, Inc. HA binding agents
NZ701915A (en) 2012-05-18 2016-11-25 Genentech Inc High-concentration monoclonal antibody formulations
US8883979B2 (en) 2012-08-31 2014-11-11 Bayer Healthcare Llc Anti-prolactin receptor antibody formulations
EP2904014A4 (en) 2012-10-04 2016-09-28 Novelmed Therapeutics Inc FOR ALTERNATIVE PATHS, SPECIFIC ANTIBODIES FOR THE TREATMENT OF HEMOLYTIC DISEASES
US20150239970A1 (en) * 2012-10-25 2015-08-27 Medimmune, Llc Stable, Low Viscosity Antibody Formulation
UA117466C2 (uk) 2012-12-13 2018-08-10 Мерк Шарп Енд Доме Корп. СТАБІЛЬНИЙ СКЛАД У ВИГЛЯДІ РОЗЧИНУ АНТИТІЛА ДО IL-23p19
IL312865B2 (en) 2013-09-11 2025-06-01 Eagle Biologics Inc Liquid protein formulations containing viscosity-lowering agents
MX2016006226A (es) 2013-11-12 2016-09-07 Sanofi Biotechnology Regimenes de dosificacion para uso con inhibidores de pcsk9.
US11357857B2 (en) 2014-06-20 2022-06-14 Comera Life Sciences, Inc. Excipient compounds for protein processing
US10478498B2 (en) 2014-06-20 2019-11-19 Reform Biologics, Llc Excipient compounds for biopolymer formulations
WO2015196091A1 (en) 2014-06-20 2015-12-23 Reform Biologics, Llc Viscosity-reducing excipient compounds for protein formulations
JP7072384B2 (ja) * 2014-09-15 2022-05-20 ジェネンテック， インコーポレイテッド 抗体製剤
EP3200804A4 (en) 2014-10-01 2018-04-18 Eagle Biologics, Inc. Polysaccharide and nucleic acid formulations containing viscosity-lowering agents
TWI738632B (zh) 2014-11-07 2021-09-11 瑞士商諾華公司 穩定的含有高濃度抗vegf抗體之蛋白質溶液調配物
EP3224341B1 (en) 2014-11-25 2021-05-19 Corning Incorporated Cell culture media extending materials and methods
JP2018500380A (ja) * 2014-12-31 2018-01-11 ノベルメド セラピューティクス，インコーポレーテッド アグリコシル化治療用抗体の製剤
PL3257524T3 (pl) * 2015-02-11 2021-03-08 Gmax Biopharm Llc Stabilny preparat farmaceutyczny w postaci roztworu białka fuzyjnego przeciwciała przeciwko glp-1r
AR103726A1 (es) 2015-02-27 2017-05-31 Merck Sharp & Dohme Cristales de anticuerpos monoclonales anti-pd-1 humanos
JP2018523684A (ja) 2015-08-18 2018-08-23 リジェネロン・ファーマシューティカルズ・インコーポレイテッドＲｅｇｅｎｅｒｏｎ Ｐｈａｒｍａｃｅｕｔｉｃａｌｓ， Ｉｎｃ． リポタンパク質アフェレーシスを受けている高脂血症の患者を治療するための抗ｐｃｓｋ９阻害抗体
US11484591B2 (en) 2016-02-22 2022-11-01 Ohio State Innovation Foundation Chemoprevention using controlled-release formulations of anti-interleukin 6 agents, synthetic vitamin A analogues or metabolites, and estradiol metabolites
CN109195629A (zh) * 2016-02-24 2019-01-11 威特拉公司 流行性感冒抗体分子制剂
GB201603280D0 (en) 2016-02-24 2016-04-13 Ferring Bv Stable liquid gonadotropin formulation
TWI826351B (zh) * 2016-05-31 2023-12-21 大陸商鴻運華寧（杭州）生物醫藥有限公司 Ｒ抗體,其藥物組合物及其應用
MX2019000177A (es) 2016-07-05 2019-06-20 Sanofi Sa Formulaciones de anticuerpos.
CR20190291A (es) 2016-12-23 2019-11-05 Serum Institute Of India Pvt Ltd Métodos mejorados para estimular la productividad de anticuerpos en el cultivo de células de mamiferos y reducir la agregación durante los procesos de formulación post-tratamiento (downstream) y formulaciones de anticuerpos estables obtenidas a partir de los mismos
KR20200012823A (ko) 2017-02-01 2020-02-05 예일 유니버시티 이뇨제 내성의 치료
US11608357B2 (en) 2018-08-28 2023-03-21 Arecor Limited Stabilized antibody protein solutions
GB201703063D0 (en) 2017-02-24 2017-04-12 Arecor Ltd Stabilized antibody protein solutions
TWI761453B (zh) 2017-03-01 2022-04-21 英商梅迪繆思有限公司 抗rsv單株抗體配製物
EP3372242A1 (en) 2017-03-06 2018-09-12 Ares Trading S.A. Liquid pharmaceutical composition
EP3372241A1 (en) 2017-03-06 2018-09-12 Ares Trading S.A. Liquid pharmaceutical composition
WO2018170405A1 (en) 2017-03-17 2018-09-20 Ohio State Innovation Foundation Nanoparticles for delivery of chemopreventive agents
WO2018181876A1 (ja) 2017-03-31 2018-10-04 Ｍｅｉｊｉ Ｓｅｉｋａファルマ株式会社 水性製剤及び注射器入り水性製剤、並びに、抗体タンパク脱凝集剤及び抗体タンパク脱凝集方法
JOP20190260A1 (ar) 2017-05-02 2019-10-31 Merck Sharp & Dohme صيغ ثابتة لأجسام مضادة لمستقبل الموت المبرمج 1 (pd-1) وطرق استخدامها
CA3063324A1 (en) 2017-05-16 2018-11-22 Bhami's Research Laboratory, Pvt. Ltd. High concentration protein formulations with reduced viscosity
KR20200044066A (ko) * 2017-08-22 2020-04-28 바이오젠 엠에이 인코포레이티드 항-알파(v)베타(6) 항체를 함유하는 약제학적 조성물 및 투약 요법
IL272773B2 (en) * 2017-08-22 2024-06-01 Biogen Ma Inc Pharmaceutical preparations containing anti-amyloid cell antibodies
JP7536640B2 (ja) 2017-11-17 2024-08-20 アムジエン・インコーポレーテツド ＶＥＧＦＲ－Ｆｃ融合タンパク質製剤
CA3087699A1 (en) 2018-01-05 2019-07-11 Corvidia Therapeutics, Inc. Methods for treating il-6 mediated inflammation without immunosuppression
US11103552B2 (en) 2018-05-10 2021-08-31 Regeneron Pharmaceuticals, Inc. High concentration VEGF receptor fusion protein containing formulations
EP3823594B1 (en) 2018-07-19 2025-02-05 Ichnos Sciences S.A. Liquid antibody formulation
JP2022527972A (ja) 2019-04-02 2022-06-07 アンスティチュ ナショナル ドゥ ラ サンテ エ ドゥ ラ ルシェルシュ メディカル 前悪性病変を有する患者において癌を予測及び予防する方法
US12024553B2 (en) * 2019-04-30 2024-07-02 Medimmune Limited Dosage regimens for and compositions including anti-RSV antibodies
KR102169901B1 (ko) * 2019-05-17 2020-10-26 연세대학교 산학협력단 Dna 메틸화를 이용한 면역 항암 요법의 치료 반응에 관한 정보 제공 방법 및 이를 이용한 키트
CN112618482A (zh) * 2019-09-24 2021-04-09 江苏恒瑞医药股份有限公司 新型蛋白制剂
EP4110290A4 (en) * 2020-02-24 2024-06-05 Medimmune, LLC ANTI-ENDOTHELIAL LIPASE ANTIBODY FORMULATIONS
KR20220156534A (ko) 2020-03-20 2022-11-25 에자이 알앤드디 매니지먼트 가부시키가이샤 고농도 항-Aβ 프로토피브릴 항체 제형물 및 이의 사용 방법
JP2023518814A (ja) 2020-03-23 2023-05-08 ジェネンテック， インコーポレイテッド Ｃｏｖｉｄ－１９肺炎における、ｉｌ－６アンタゴニストに対する応答を予測するためのバイオマーカー
JP2023518815A (ja) 2020-03-23 2023-05-08 ジェネンテック， インコーポレイテッド Ｉｌ６アンタゴニストによるｃｏｖｉｄ－１９肺炎を含む肺炎の治療方法
JP2023518812A (ja) 2020-03-23 2023-05-08 ジェネンテック， インコーポレイテッド Ｃｏｖｉｄ１９肺炎を治療するための、トシリズマブとレムデシビルとの組み合わせ
KR20220028972A (ko) * 2020-08-31 2022-03-08 (주)셀트리온 안정한 약제학적 제제
CN116685351A (zh) 2020-09-17 2023-09-01 基因泰克公司 Empacta的结果：一项用于评估托珠单抗在患有covid-19肺炎的住院患者中的功效和安全性的随机、双盲、安慰剂对照、多中心研究
WO2022098750A1 (en) * 2020-11-03 2022-05-12 La Jolla Institute For Immunology Hla class ii-restricted tcrs against the kras g12>v activating mutation
US20220332822A1 (en) * 2021-04-16 2022-10-20 Tiziana Life Sciences Plc Subcutaneous administration of antibodies for the treatment of disease
AU2023367497A1 (en) * 2022-10-26 2025-05-15 Nihon Medi-Physics Co., Ltd. Radioactive pharmaceutical composition
US20240245779A1 (en) 2023-01-25 2024-07-25 Regeneron Pharmaceuticals, Inc. Methods of modeling liquid protein composition stability
CN120752144A (zh) 2023-03-30 2025-10-03 三菱化学株式会社 喷墨记录方法

Citations (28)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0239400A2 (en) 1986-03-27 1987-09-30 Medical Research Council Recombinant antibodies and methods for their production
JPH0159878B2 (https=) 1982-05-21 1989-12-20 Yunibaashitei Obu Karifuorunia
WO1992001047A1 (en) 1990-07-10 1992-01-23 Cambridge Antibody Technology Limited Methods for producing members of specific binding pairs
WO1992003918A1 (en) 1990-08-29 1992-03-19 Genpharm International, Inc. Transgenic non-human animals capable of producing heterologous antibodies
WO1992019759A1 (fr) 1991-04-25 1992-11-12 Chugai Seiyaku Kabushiki Kaisha Anticorps humains reconstitues diriges contre un recepteur de l'interleukine 6 humaine
WO1992020791A1 (en) 1990-07-10 1992-11-26 Cambridge Antibody Technology Limited Methods for producing members of specific binding pairs
WO1993006213A1 (en) 1991-09-23 1993-04-01 Medical Research Council Production of chimeric antibodies - a combinatorial approach
WO1993011236A1 (en) 1991-12-02 1993-06-10 Medical Research Council Production of anti-self antibodies from antibody segment repertoires and displayed on phage
WO1993012227A1 (en) 1991-12-17 1993-06-24 Genpharm International, Inc. Transgenic non-human animals capable of producing heterologous antibodies
WO1993019172A1 (en) 1992-03-24 1993-09-30 Cambridge Antibody Technology Limited Methods for producing members of specific binding pairs
WO1994002602A1 (en) 1992-07-24 1994-02-03 Cell Genesys, Inc. Generation of xenogeneic antibodies
WO1994025585A1 (en) 1993-04-26 1994-11-10 Genpharm International, Inc. Transgenic non-human animals capable of producing heterologous antibodies
WO1995001438A1 (en) 1993-06-30 1995-01-12 Medical Research Council Sbp members with a chemical moiety covalently bound within the binding site; production and selection thereof
WO1995015388A1 (en) 1993-12-03 1995-06-08 Medical Research Council Recombinant binding proteins and peptides
WO1996002576A1 (en) 1994-07-13 1996-02-01 Chugai Seiyaku Kabushiki Kaisha Reconstituted human antibody against human interleukin-8
JPH0899902A (ja) 1994-09-30 1996-04-16 Chugai Pharmaceut Co Ltd Ｉｌ−６レセプター抗体を有効成分とする未熟型骨髄腫細胞治療剤
WO1996033735A1 (en) 1995-04-27 1996-10-31 Abgenix, Inc. Human antibodies derived from immunized xenomice
WO1996034096A1 (en) 1995-04-28 1996-10-31 Abgenix, Inc. Human antibodies derived from immunized xenomice
WO1998013388A1 (en) 1996-09-26 1998-04-02 Chugai Seiyaku Kabushiki Kaisha Antibody against human parathormone related peptides
WO1998014580A1 (en) 1996-10-04 1998-04-09 Chugai Seiyaku Kabushiki Kaisha Reconstituted human anti-hm1.24 antibody
WO1999051743A1 (en) 1998-04-03 1999-10-14 Chugai Seiyaku Kabushiki Kaisha Humanized antibody against human tissue factor (tf) and process for constructing humanized antibody
WO2001066737A1 (en) 2000-03-10 2001-09-13 Chugai Seiyaku Kabushiki Kaisha Polypeptide inducing apoptosis
WO2002013860A1 (en) * 2000-08-11 2002-02-21 Chugai Seiyaku Kabushiki Kaisha Stabilized antibody-containing preparations
WO2002033072A1 (fr) 2000-10-20 2002-04-25 Chugai Seiyaku Kabushiki Kaisha Anticorps degrade, agoniste de tpo
WO2005005636A1 (ja) 2003-07-15 2005-01-20 Chugai Seiyaku Kabushiki Kaisha 形質転換細胞によるIｇMの産生とその定量方法
JP2005527503A (ja) * 2002-02-27 2005-09-15 イミユネツクス・コーポレイシヨン ポリペプチド製剤
JP2007511566A (ja) * 2003-11-18 2007-05-10 ツェットエルベー ベーリング アクチエンゲゼルシャフト 安定性を高めた免疫グロブリン配合物
JP2007204498A (ja) * 1999-03-01 2007-08-16 Chugai Pharmaceut Co Ltd 長期安定化製剤

Family Cites Families (98)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS55106216A (en) 1979-02-09 1980-08-14 Hitachi Chem Co Ltd Preparation of amino resin
JPS63453A (ja) 1986-06-20 1988-01-05 Tohoku Metal Ind Ltd 耐酸化性永久磁石材料とその製造方法
US6428979B1 (en) 1988-01-22 2002-08-06 Tadamitsu Kishimoto Receptor protein for human B cell stimulatory factor-2
US5670373A (en) 1988-01-22 1997-09-23 Kishimoto; Tadamitsu Antibody to human interleukin-6 receptor
US5171840A (en) 1988-01-22 1992-12-15 Tadamitsu Kishimoto Receptor protein for human B cell stimulatory factor-2
US5158761A (en) * 1989-04-05 1992-10-27 Toko Yakuhin Kogyo Kabushiki Kaisha Spray gel base and spray gel preparation using thereof
US5888510A (en) 1993-07-21 1999-03-30 Chugai Seiyaku Kabushiki Kaisha Chronic rheumatoid arthritis therapy containing IL-6 antagonist as effective component
US8017121B2 (en) 1994-06-30 2011-09-13 Chugai Seiyaku Kabushika Kaisha Chronic rheumatoid arthritis therapy containing IL-6 antagonist as effective component
CN1306963C (zh) 1994-10-21 2007-03-28 岸本忠三 用于治疗il－6产生所致疾病的药物组合物
EP0800829B2 (en) 1994-12-29 2012-07-25 Chugai Seiyaku Kabushiki Kaisha Use of a pm-1 antibody or of a mh 166 antibody for enhancing the anti-tumor effect of cisplatin or carboplatin
ES2264135T3 (es) 1995-02-13 2006-12-16 Chugai Seiyaku Kabushiki Kaisha Inhibidor de la descomposicion de proteinas musculares que contienen anticuerpos frente al receptor de il-6.
DK0923941T3 (da) 1996-06-27 2006-09-18 Chugai Pharmaceutical Co Ltd Midler mod myelom der skal anvendes sammen med nitrogensennepantitumormidler
AU736282B2 (en) 1997-03-21 2001-07-26 Chugai Seiyaku Kabushiki Kaisha A preventive or therapeutic agent for sensitized T cell- mediated diseases comprising IL-6 antagonist as an active ingredient
US6991790B1 (en) 1997-06-13 2006-01-31 Genentech, Inc. Antibody formulation
US20020187150A1 (en) 1997-08-15 2002-12-12 Chugai Seiyaku Kabushiki Kaisha Preventive and/or therapeutic agent for systemic lupus erythematosus comprising anti-IL-6 receptor antibody as an active ingredient
DK1074268T3 (da) 1998-03-17 2008-04-28 Chugai Pharmaceutical Co Ltd IL-6-receptorantagonistantistofholdige forebyggende eller terapeutiske midler mod inflammatoriske tarmsygdomme
US6537782B1 (en) 1998-06-01 2003-03-25 Chugai Seiyaku Kabushiki Kaisha Media for culturing animal cells and process for producing protein by using the same
US6406909B1 (en) 1998-07-10 2002-06-18 Chugai Seiyaku Kabushiki Kaisha Serum-free medium for culturing animal cells
ATE350060T1 (de) 1998-08-24 2007-01-15 Chugai Pharmaceutical Co Ltd Mittel zur vorbeugung oder behandlung von pankreatitis die anti-il-6 receptor antikörper als aktive komponente enthalten
JP2000247903A (ja) * 1999-03-01 2000-09-12 Chugai Pharmaceut Co Ltd 長期安定化製剤
US6914128B1 (en) * 1999-03-25 2005-07-05 Abbott Gmbh & Co. Kg Human antibodies that bind human IL-12 and methods for producing
DE60031999T2 (de) 1999-10-04 2007-06-06 Novartis Vaccines and Diagnostics, Inc., Emeryville Stabilisierte flüssige polypeptid-haltige pharmazeutische zusammensetzungen
AU2001236005A1 (en) 2000-02-29 2001-09-12 Chugai Seiyaku Kabushiki Kaisha Preparations stabilized over long time
AU2001278716A1 (en) 2000-08-10 2002-02-25 Chugai Seiyaku Kabushiki Kaisha Method of inhibiting antibody-containing solution from coagulating or becoming turbid
EP1930024A3 (en) 2000-09-01 2008-08-06 Chugai Seiyaku Kabushiki Kaisha G-CSF solution formulations having long-term stability
US8703126B2 (en) 2000-10-12 2014-04-22 Genentech, Inc. Reduced-viscosity concentrated protein formulations
AU2002213441B2 (en) * 2000-10-12 2006-10-26 Genentech, Inc. Reduced-viscosity concentrated protein formulations
DE60133029T2 (de) 2000-10-25 2009-03-12 Chugai Seiyaku K.K. Mittel zur prävention oder behandlung von psoriasis mit einem il-6-antagonist als wirkstoff
WO2002036165A1 (fr) 2000-10-27 2002-05-10 Chugai Seiyaku Kabushiki Kaisha Agent à base d'antagoniste d'il-6, faisant baisser le niveau des mmp-3 dans le sang
WO2002036164A1 (en) 2000-10-27 2002-05-10 Chugai Seiyaku Kabushiki Kaisha Blooe vegf level-lowering agent containing il-6 antagonist as the active ingredient
EP3088412B1 (en) 2001-03-09 2021-05-05 Chugai Seiyaku Kabushiki Kaisha Protein purification method
UA80091C2 (en) 2001-04-02 2007-08-27 Chugai Pharmaceutical Co Ltd Remedies for infant chronic arthritis-relating diseases and still's disease which contain an interleukin-6 (il-6) antagonist
CA2454587C (en) * 2001-07-25 2012-11-13 Protein Design Labs, Inc. Stable lyophilized pharmaceutical formulation of igg antibodies
JP5290489B2 (ja) 2001-11-08 2013-09-18 アッヴィ・バイオセラピューティクス・インコーポレイテッド Ｉｇｇ抗体の安定な液体医薬製剤
BRPI0214168B8 (pt) * 2001-11-14 2021-05-25 Centocor Inc anticorpos anti-il-6, moléculas de ácido nucleico codificando os mesmos, vetores compreendendo as referidas moléculas, composições e formulações compreendendo os referidos anticorpos, bem como métodos de produção dos mesmos
US20030138416A1 (en) * 2001-12-03 2003-07-24 Jesper Lau Use of glucokinase activator in combination with a glucagon antagonist for treating type 2 diabetes
AU2003211990A1 (en) 2002-02-14 2003-09-04 Chugai Seiyaku Kabushiki Kaisha Antibody-containing solution pharmaceuticals
JP3822137B2 (ja) 2002-05-20 2006-09-13 中外製薬株式会社 動物細胞培養用培地の添加剤およびそれを用いたタンパク質の製造方法
AU2003259995B2 (en) 2002-08-28 2009-07-02 Immunex Corporation Compositions and methods for treating cardiovascular disease
ES2558303T3 (es) 2002-09-11 2016-02-03 Chugai Seiyaku Kabushiki Kaisha Método de purificación de proteínas
DE10255508A1 (de) 2002-11-27 2004-06-17 Forschungszentrum Jülich GmbH Verfahren zur Kultivierung von Zellen zur Produktion von Substanzen
AU2003293543A1 (en) 2002-12-13 2004-07-09 Abgenix, Inc. System and method for stabilizing antibodies with histidine
AU2004212843B2 (en) 2003-02-24 2009-06-25 Chugai Seiyaku Kabushiki Kaisha Remedy for spinal injury containing interleukin-6 antagonist
US20050158303A1 (en) 2003-04-04 2005-07-21 Genentech, Inc. Methods of treating IgE-mediated disorders comprising the administration of high concentration anti-IgE antibody formulations
CN1798575A (zh) 2003-04-04 2006-07-05 健泰科生物技术公司 高浓度抗体和蛋白制剂
GB2401040A (en) 2003-04-28 2004-11-03 Chugai Pharmaceutical Co Ltd Method for treating interleukin-6 related diseases
KR101193708B1 (ko) 2003-10-17 2012-10-22 추가이 세이야쿠 가부시키가이샤 중피종 치료제
DE10355251A1 (de) 2003-11-26 2005-06-23 Merck Patent Gmbh Pharmazeutische Zubereitung enthaltend einen Antikörper gegen den EGF-Rezeptor
US8617550B2 (en) 2003-12-19 2013-12-31 Chugai Seiyaku Kabushiki Kaisha Treatment of vasculitis with IL-6 antagonist
AR048210A1 (es) 2003-12-19 2006-04-12 Chugai Pharmaceutical Co Ltd Un agente preventivo para la vasculitis.
WO2005063291A1 (ja) * 2003-12-25 2005-07-14 Kirin Beer Kabushiki Kaisha 抗体を含有する安定な水性医薬製剤
RU2390353C2 (ru) 2004-02-12 2010-05-27 Мерк Патент Гмбх Высококонцентрированные жидкие композиции анти-egfr антител
WO2005089503A2 (en) * 2004-03-19 2005-09-29 Progenics Pharmaceuticals, Inc. Cd4-igg2 formulations
AR048335A1 (es) 2004-03-24 2006-04-19 Chugai Pharmaceutical Co Ltd Agentes terapeuticos para trastornos del oido interno que contienen un antagonista de il- 6 como un ingrediente activo
US8398980B2 (en) 2004-03-24 2013-03-19 Chugai Seiyaku Kabushiki Kaisha Subtypes of humanized antibody against interleuken-6 receptor
PT1778723E (pt) * 2004-08-17 2013-01-25 Regeneron Pharma Formulações de antagonista de il-1
JO3000B1 (ar) 2004-10-20 2016-09-05 Genentech Inc مركبات أجسام مضادة .
JP4818936B2 (ja) 2005-01-05 2011-11-16 中外製薬株式会社 細胞の培養方法およびその利用
BRPI0606867A2 (pt) 2005-01-28 2009-07-21 Wyeth Corp formulação lìquida; forma de dosagem unitária farmacêutica; kit; recipiente; método para aumentar a estabilidade de um polipeptìdeo de ligação a antìgeno numa formulação; método para preparar uma forma de dosagem unitária farmacêutica; formulação estável; formulação; e produto terapêutico
EP1871806A2 (en) * 2005-03-08 2008-01-02 Pharmacia & Upjohn Company LLC ANTI-MAdCAM ANTIBODY COMPOSITIONS
WO2007019232A2 (en) 2005-08-03 2007-02-15 Immunogen, Inc. Immunoconjugate formulations
RU2446826C2 (ru) 2005-10-14 2012-04-10 Фукуока Юниверсити Агенты для подавления повреждения трансплантированных островков после трансплантации островков
AR058135A1 (es) 2005-10-21 2008-01-23 Chugai Pharmaceutical Co Ltd Agentes para el tratamiento de cardiopatias
AR057582A1 (es) 2005-11-15 2007-12-05 Nat Hospital Organization Agentes para suprimir la induccion de linfocitos t citotoxicos
TW200803894A (en) 2005-11-25 2008-01-16 Univ Keio Prostate cancer therapeutic agents
US9084777B2 (en) 2005-12-28 2015-07-21 Chugai Seiyaku Kabushiki Kaisha Stabilized antibody-containing formulations
CA2637917C (en) 2006-01-27 2015-11-24 Keio University Therapeutic agents for diseases involving choroidal neovascularization
CA2638811A1 (en) * 2006-02-03 2007-08-16 Medimmune, Llc Protein formulations
WO2007101661A1 (en) 2006-03-09 2007-09-13 F.Hoffmann-La Roche Ag Anti-drug antibody assay
TW200806317A (en) 2006-03-20 2008-02-01 Wyeth Corp Methods for reducing protein aggregation
EP2025346B1 (en) 2006-04-07 2016-08-10 Osaka University Muscle regeneration promoter
MX2008013508A (es) * 2006-04-21 2008-10-31 Novartis Ag Composiciones farmaceuticas de anticuerpos antagonistas anti-cd40.
WO2008016134A1 (fr) 2006-08-04 2008-02-07 Norihiro Nishimoto PROCÉDÉ POUR PRÉDIRE LE PRONOSTIC DES PATIENTS ATTEINTS DE POLYARTHRITE rhumatoïde
JP2010095445A (ja) 2006-12-27 2010-04-30 Tokyo Medical & Dental Univ Ｉｌ−６アンタゴニストを有効成分とする炎症性筋疾患治療剤
CA2674608A1 (en) 2007-01-09 2008-07-17 Wyeth Anti-il-13 antibody formulations and uses thereof
WO2008090901A1 (ja) 2007-01-23 2008-07-31 Shinshu University 慢性拒絶反応抑制剤
EP2174667B1 (en) 2007-07-26 2017-01-04 Osaka University Agent for treatment of ophthalmia containing interleukin-6 receptor inhibitor as active ingredient
EP2206775B1 (en) 2007-09-26 2016-06-29 Chugai Seiyaku Kabushiki Kaisha Anti-il-6 receptor antibody
CA2701155C (en) 2007-10-02 2016-11-22 Chugai Seiyaku Kabushiki Kaisha Therapeutic agents for graft-versus-host disease comprising interleukin 6 receptor inhibitor as active ingredient
JP2009092508A (ja) 2007-10-09 2009-04-30 Norihiro Nishimoto リウマチ治療剤の効果の予測方法
ES2407603T3 (es) 2007-12-15 2013-06-13 F. Hoffmann-La Roche Ag Ensayo de distinción
PE20091174A1 (es) * 2007-12-27 2009-08-03 Chugai Pharmaceutical Co Ltd Formulacion liquida con contenido de alta concentracion de anticuerpo
TWI528973B (zh) 2008-06-05 2016-04-11 Chugai Pharmaceutical Co Ltd Nerve infiltration inhibitor
TWI440469B (zh) 2008-09-26 2014-06-11 Chugai Pharmaceutical Co Ltd Improved antibody molecules
AU2010278067B2 (en) 2009-07-31 2016-10-27 Shin Maeda Cancer metastasis inhibitor
WO2011051231A1 (en) 2009-10-26 2011-05-05 F. Hoffmann-La Roche Ag Method for the production of a glycosylated immunoglobulin
AR080428A1 (es) 2010-01-20 2012-04-11 Chugai Pharmaceutical Co Ltd Formulaciones liquidas estabilizadas contentivas de anticuerpos
WO2011128096A1 (en) 2010-04-16 2011-10-20 Roche Diagnostics Gmbh Polymorphism markers for predicting response to interleukin-6 receptor-inhibiting monoclonal antibody drug treatment
JP6051049B2 (ja) 2010-05-28 2016-12-21 中外製薬株式会社 抗腫瘍ｔ細胞応答増強剤
WO2011149046A1 (ja) 2010-05-28 2011-12-01 独立行政法人国立がん研究センター 膵癌治療剤
CA2801107A1 (en) 2010-06-07 2011-12-15 F. Hoffman-La Roche Ag Gene expression markers for predicting response to interleukin-6 receptor-inhibiting monoclonal antibody drug treatment
TWI603738B (zh) 2010-11-08 2017-11-01 建南德克公司 皮下投予抗－ｉｌ－６受體抗體
KR101993488B1 (ko) 2011-09-01 2019-06-26 추가이 세이야쿠 가부시키가이샤 한외여과에 의해 고도로 농축된 항체를 포함하는 조성물의 제조 방법
CN105378480B (zh) 2013-07-04 2018-06-12 豪夫迈·罗氏有限公司 检测血清样品中抗药物抗体的干扰抑制性免疫测定
US10349940B2 (en) 2015-08-24 2019-07-16 Ethicon Llc Surgical stapler buttress applicator with state indicator
US10961314B2 (en) 2016-09-27 2021-03-30 Fresenius Kabi Deutschland Gmbh Liquid pharmaceutical composition comprising an anti-IL-6 receptor antibody
CN110062620B (zh) 2016-10-31 2023-12-05 德国费森尤斯卡比有限公司 液体药物组合物
BR112020010761A2 (pt) 2017-11-30 2020-11-24 Bio-Thera Solutions, Ltd. formulação líquida de anticorpo humanizado para o tratamento de doenças relacionadas à il-6

Patent Citations (28)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH0159878B2 (https=) 1982-05-21 1989-12-20 Yunibaashitei Obu Karifuorunia
EP0239400A2 (en) 1986-03-27 1987-09-30 Medical Research Council Recombinant antibodies and methods for their production
WO1992001047A1 (en) 1990-07-10 1992-01-23 Cambridge Antibody Technology Limited Methods for producing members of specific binding pairs
WO1992020791A1 (en) 1990-07-10 1992-11-26 Cambridge Antibody Technology Limited Methods for producing members of specific binding pairs
WO1992003918A1 (en) 1990-08-29 1992-03-19 Genpharm International, Inc. Transgenic non-human animals capable of producing heterologous antibodies
WO1992019759A1 (fr) 1991-04-25 1992-11-12 Chugai Seiyaku Kabushiki Kaisha Anticorps humains reconstitues diriges contre un recepteur de l'interleukine 6 humaine
WO1993006213A1 (en) 1991-09-23 1993-04-01 Medical Research Council Production of chimeric antibodies - a combinatorial approach
WO1993011236A1 (en) 1991-12-02 1993-06-10 Medical Research Council Production of anti-self antibodies from antibody segment repertoires and displayed on phage
WO1993012227A1 (en) 1991-12-17 1993-06-24 Genpharm International, Inc. Transgenic non-human animals capable of producing heterologous antibodies
WO1993019172A1 (en) 1992-03-24 1993-09-30 Cambridge Antibody Technology Limited Methods for producing members of specific binding pairs
WO1994002602A1 (en) 1992-07-24 1994-02-03 Cell Genesys, Inc. Generation of xenogeneic antibodies
WO1994025585A1 (en) 1993-04-26 1994-11-10 Genpharm International, Inc. Transgenic non-human animals capable of producing heterologous antibodies
WO1995001438A1 (en) 1993-06-30 1995-01-12 Medical Research Council Sbp members with a chemical moiety covalently bound within the binding site; production and selection thereof
WO1995015388A1 (en) 1993-12-03 1995-06-08 Medical Research Council Recombinant binding proteins and peptides
WO1996002576A1 (en) 1994-07-13 1996-02-01 Chugai Seiyaku Kabushiki Kaisha Reconstituted human antibody against human interleukin-8
JPH0899902A (ja) 1994-09-30 1996-04-16 Chugai Pharmaceut Co Ltd Ｉｌ−６レセプター抗体を有効成分とする未熟型骨髄腫細胞治療剤
WO1996033735A1 (en) 1995-04-27 1996-10-31 Abgenix, Inc. Human antibodies derived from immunized xenomice
WO1996034096A1 (en) 1995-04-28 1996-10-31 Abgenix, Inc. Human antibodies derived from immunized xenomice
WO1998013388A1 (en) 1996-09-26 1998-04-02 Chugai Seiyaku Kabushiki Kaisha Antibody against human parathormone related peptides
WO1998014580A1 (en) 1996-10-04 1998-04-09 Chugai Seiyaku Kabushiki Kaisha Reconstituted human anti-hm1.24 antibody
WO1999051743A1 (en) 1998-04-03 1999-10-14 Chugai Seiyaku Kabushiki Kaisha Humanized antibody against human tissue factor (tf) and process for constructing humanized antibody
JP2007204498A (ja) * 1999-03-01 2007-08-16 Chugai Pharmaceut Co Ltd 長期安定化製剤
WO2001066737A1 (en) 2000-03-10 2001-09-13 Chugai Seiyaku Kabushiki Kaisha Polypeptide inducing apoptosis
WO2002013860A1 (en) * 2000-08-11 2002-02-21 Chugai Seiyaku Kabushiki Kaisha Stabilized antibody-containing preparations
WO2002033072A1 (fr) 2000-10-20 2002-04-25 Chugai Seiyaku Kabushiki Kaisha Anticorps degrade, agoniste de tpo
JP2005527503A (ja) * 2002-02-27 2005-09-15 イミユネツクス・コーポレイシヨン ポリペプチド製剤
WO2005005636A1 (ja) 2003-07-15 2005-01-20 Chugai Seiyaku Kabushiki Kaisha 形質転換細胞によるIｇMの産生とその定量方法
JP2007511566A (ja) * 2003-11-18 2007-05-10 ツェットエルベー ベーリング アクチエンゲゼルシャフト 安定性を高めた免疫グロブリン配合物

Non-Patent Citations (9)

* Cited by examiner, † Cited by third party
Title
BETTER, M.; HORWITZ, A. H., METHODS ENZYMOL., vol. 178, 1989, pages 476 - 496
BIRD, R. E.; WALKER, B. W., TRENDS BIOTECHNOL., vol. 9, 1991, pages 132 - 137
CO, M. S. ET AL., T. IMMUNOL., vol. 152, 1994, pages 2968 - 2976
HUSTON, J. S. ET AL., PROC. NATL. ACAD. SCI. U.S.A., vol. 85, 1988, pages 5879 - 5883
KOHLER. G.; MILSTEIN, C., METHODS ENZYMOL., vol. 73, 1981, pages 3 - 46
LAMOYI, E., METHODS ENZYMOL, vol. 121, 1986, pages 652 - 663
PLUCKTHUN, A.; SKERRA, A., METHODS ENZYMOL., vol. 178, 1989, pages 497 - 515
ROUSSEAUX, J. ET AL., METHODS ENZYMOL., vol. 121, 1986, pages 663 - 669
SATO, K. ET AL., CANCER RES., vol. 53, 1993, pages 851 - 856

Cited By (134)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9051384B2 (en) 2002-02-14 2015-06-09 Chugai Seiyaku Kabushiki Kaisha Antibody-containing solution formulations
US8840884B2 (en) 2002-02-14 2014-09-23 Chugai Seiyaku Kabushiki Kaisha Antibody-containing solution pharmaceuticals
US11168344B2 (en) 2005-03-31 2021-11-09 Chugai Seiyaku Kabushiki Kaisha Methods for producing polypeptides by regulating polypeptide association
US10934344B2 (en) 2006-03-31 2021-03-02 Chugai Seiyaku Kabushiki Kaisha Methods of modifying antibodies for purification of bispecific antibodies
US12473375B2 (en) 2006-03-31 2025-11-18 Chugai Seiyaku Kabushiki Kaisha Methods for controlling blood pharmacokinetics of antibodies
US11046784B2 (en) 2006-03-31 2021-06-29 Chugai Seiyaku Kabushiki Kaisha Methods for controlling blood pharmacokinetics of antibodies
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US11248053B2 (en) 2007-09-26 2022-02-15 Chugai Seiyaku Kabushiki Kaisha Method of modifying isoelectric point of antibody via amino acid substitution in CDR
US12122840B2 (en) 2007-09-26 2024-10-22 Chugai Seiyaku Kabushiki Kaisha Method of modifying isoelectric point of antibody via amino acid substitution in CDR
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US11359026B2 (en) 2007-12-27 2022-06-14 Chugai Seiyaku Kabushiki Kaisha High concentration antibody-containing liquid formulation
US11584798B2 (en) 2007-12-27 2023-02-21 Hoffmann-La Roche Inc. High concentration antibody-containing liquid formulation
JP2012072170A (ja) * 2007-12-27 2012-04-12 Chugai Pharmaceut Co Ltd 高濃度抗体含有溶液製剤
US11767363B2 (en) 2007-12-27 2023-09-26 Chugai Seiyaku Kabushiki Kaisha High concentration antibody-containing liquid formulation
US8568720B2 (en) 2007-12-27 2013-10-29 Chugai Seiyaku Kabushiki Kaisha High concentration antibody-containing liquid formulation
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US11021728B2 (en) 2009-10-26 2021-06-01 Hoffmann-La Roche Inc. Method for the production of a glycosylated immunoglobulin
US10501769B2 (en) 2009-10-26 2019-12-10 Hoffmann-La Roche Inc. Method for the production of a glycosylated immunoglobulin
US11377678B2 (en) 2009-10-26 2022-07-05 Hoffman-La Roche Inc. Method for the production of a glycosylated immunoglobulin
US11136610B2 (en) 2009-10-26 2021-10-05 Hoffmann-La Roche Inc. Method for the production of a glycosylated immunoglobulin
AU2010339770B2 (en) * 2009-12-21 2015-02-12 Genentech, Inc. Antibody formulation
AU2013202276B2 (en) * 2009-12-21 2016-03-24 Genentech, Inc. Antibody formulation
JP2018035170A (ja) * 2009-12-21 2018-03-08 ジェネンテック， インコーポレイテッド 抗体製剤
JP2013515071A (ja) * 2009-12-21 2013-05-02 ジェネンテック， インコーポレイテッド 抗体製剤
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US9226961B2 (en) 2009-12-21 2016-01-05 Genentech, Inc. Antibody formulation
EP3616719A1 (en) * 2009-12-21 2020-03-04 F. Hoffmann-La Roche AG Antibody formulation
JP2015232001A (ja) * 2009-12-21 2015-12-24 ジェネンテック， インコーポレイテッド 抗体製剤
WO2011084750A1 (en) * 2009-12-21 2011-07-14 Genentech, Inc. Antibody formulation
JP2021050215A (ja) * 2010-11-08 2021-04-01 ジェネンテック， インコーポレイテッド 皮下投与される抗ｉｌ−６受容体抗体
US11667720B1 (en) 2010-11-08 2023-06-06 Hoffmann-La Roche Inc. Subcutaneously administered anti-IL-6 receptor antibody
JP2023036669A (ja) * 2010-11-08 2023-03-14 ジェネンテック， インコーポレイテッド 皮下投与される抗ｉｌ－６受容体抗体
US11622969B2 (en) 2010-11-08 2023-04-11 Hoffmann-La Roche Inc. Subcutaneously administered anti-IL-6 receptor antibody
US10450381B2 (en) 2010-11-17 2019-10-22 Chugai Seiyaku Kabushiki Kaisha Methods of treatment that include the administration of bispecific antibodies
JP2014516924A (ja) * 2011-04-07 2014-07-17 グラクソスミスクライン・リミテッド・ライアビリティ・カンパニー 粘度が低減された処方物
WO2013012022A1 (ja) 2011-07-19 2013-01-24 中外製薬株式会社 アルギニンアミドまたはその類似化合物を含む安定なタンパク質含有製剤
US9574005B2 (en) 2011-07-19 2017-02-21 Chugai Seiyaku Kabushiki Kaisha Stable Protein-containing preparation containing argininamide or analogous compound thereof
US10898572B2 (en) 2011-07-19 2021-01-26 Chugai Seiyaku Kabushiki Kaisha Stable protein-containing preparation containing argininamide or analogous compound thereof
WO2013031237A1 (en) 2011-09-01 2013-03-07 Chugai Seiyaku Kabushiki Kaisha Method for preparing a composition comprising highly concentrated antibodies by ultrafiltration
EP3235557A1 (en) 2011-09-01 2017-10-25 Chugai Seiyaku Kabushiki Kaisha Method for preparing a composition comprising highly concentrated antibodies by ultrafiltration
JPWO2014010586A1 (ja) * 2012-07-10 2016-06-23 武田薬品工業株式会社 注射用製剤
US10786566B2 (en) 2012-09-07 2020-09-29 Coherus Biosciences, Inc. Stable aqueous formulations of adalimumab
US10159732B2 (en) 2012-09-07 2018-12-25 Coherus Biosciences, Inc. Stable aqueous formulations of adalimumab
US10716853B2 (en) 2012-09-07 2020-07-21 Coherus Biosciences, Inc. Stable aqueous formulations of adalimumab
US10722579B2 (en) 2012-09-07 2020-07-28 Coherus Biosciences, Inc. Stable aqueous formulations of adalimumab
US10207000B2 (en) 2012-09-07 2019-02-19 Coherus Biosciences, Inc. Stable aqueous formulations of adalimumab
US10286071B2 (en) 2012-09-07 2019-05-14 Coherus Biosciences, Inc. Syringe containing stable aqueous formulations of adalimumab
US10286072B2 (en) 2012-09-07 2019-05-14 Coherus Biosciences, Inc. Methods of manufacturing stable aqueous formulations of adalimumab
US10772959B2 (en) 2012-09-07 2020-09-15 Coherus Biosciences, Inc. Stable aqueous formulations of adalimumab
US10772960B2 (en) 2012-09-07 2020-09-15 Coherus Biosciences, Inc. Stable aqueous formulations of adalimumab
US10716852B2 (en) 2012-09-07 2020-07-21 Coherus Biosciences, Inc. Stable aqueous formulations of adalimumab
US10780163B2 (en) 2012-09-07 2020-09-22 Coherus Biosciences, Inc. Stable aqueous formulations of adalimumab
US10195275B2 (en) 2012-09-07 2019-02-05 Coherus Biosciences, Inc. Stable aqueous formulations of adalimumab
US10799585B2 (en) 2012-09-07 2020-10-13 Coherus Biosciences, Inc. Stable aqueous formulations of adalimumab
JP2015527402A (ja) * 2012-09-07 2015-09-17 コヒラス・バイオサイエンシズ・インコーポレイテッド 安定水性アダリムマブ製剤
US10688183B2 (en) 2012-09-07 2020-06-23 Coherus Biosciences, Inc. Stable aqueous formulations of adalimumab
US10716854B2 (en) 2012-09-07 2020-07-21 Coherus Biosciences, Inc. Stable aqueous formulations of adalimumab
US10159733B2 (en) 2012-09-07 2018-12-25 Coherus Biosciences, Inc. Stable aqueous formulations of adalimumab
US10155039B2 (en) 2012-09-07 2018-12-18 Coherus Biosciences, Inc. Stable aqueous formulations of adalimumab
US10168326B2 (en) 2013-07-04 2019-01-01 F. Hoffmann-La Roche Inc. Interference-suppressed immunoassay to detect anti-drug antibodies in serum samples
US10761091B2 (en) 2013-07-04 2020-09-01 Hoffmann-La Roche, Inc. Interference-suppressed immunoassay to detect anti-drug antibodies in serum samples
US11124576B2 (en) 2013-09-27 2021-09-21 Chungai Seiyaku Kabushiki Kaisha Method for producing polypeptide heteromultimer
JP7277681B2 (ja) 2014-05-16 2023-05-19 グラクソスミスクライン、インテレクチュアル、プロパティー、マネジメント、リミテッド 抗体処方物
JP2020114819A (ja) * 2014-05-16 2020-07-30 グラクソスミスクライン、インテレクチュアル、プロパティー、マネジメント、リミテッドＧｌａｘｏｓｍｉｔｈｋｌｉｎｅ Ｉｎｔｅｌｌｅｃｔｕａｌ Ｐｒｏｐｅｒｔｙ Ｍａｎａｇｅｍｅｎｔ Ｌｉｍｉｔｅｄ 抗体処方物
US11214623B2 (en) 2014-09-26 2022-01-04 Chugai Seiyaku Kabushiki Kaisha Antibody capable of neutralizing substance having activity alternative to function of coagulation factor VIII (FVIII)
US11150254B2 (en) 2014-09-26 2021-10-19 Chugai Seiyaku Kabushiki Kaisha Method for measuring reactivity of FVIII
US12599664B2 (en) 2014-12-22 2026-04-14 Novartis Ag Pharmaceutical products and stable liquid compositions of IL-17 antibodies
US12485173B2 (en) 2014-12-22 2025-12-02 Novartis Ag Pharmaceutical products and stable liquid compositions of IL-17 antibodies
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US11801300B2 (en) 2014-12-22 2023-10-31 Novartis Ag Pharmaceutical products and stable liquid compositions of IL-17 antibodies
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US12296008B2 (en) 2014-12-22 2025-05-13 Novartis Ag Pharmaceutical products and stable liquid compositions of IL-17 antibodies
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US12359001B2 (en) 2015-04-01 2025-07-15 Chugai Seiyaku Kabushiki Kaisha Method for producing polypeptide hetero-oligomer
WO2017057644A1 (ja) * 2015-09-30 2017-04-06 持田製薬株式会社 高濃度抗体含有液体製剤
US11229702B1 (en) 2015-10-28 2022-01-25 Coherus Biosciences, Inc. High concentration formulations of adalimumab
JP2021127348A (ja) * 2015-12-18 2021-09-02 アステラス製薬株式会社 抗ヒトｔｓｌｐ受容体抗体含有医薬組成物
US10994011B2 (en) 2015-12-18 2021-05-04 Astellas Pharma Inc. Pharmaceutical composition comprising anti-human TSLP receptor antibody
US12447210B2 (en) 2015-12-18 2025-10-21 Upstream Bio, Inc. Pharmaceutical composition comprising anti-human TSLP receptor antibody
EP4506016A3 (en) * 2015-12-18 2025-06-04 Upstream Bio, Inc. Pharmaceutical composition containing anti-human tslp receptor antibody
JPWO2017104778A1 (ja) * 2015-12-18 2018-10-04 アステラス製薬株式会社 抗ヒトｔｓｌｐ受容体抗体含有医薬組成物
CN108430507B (zh) * 2015-12-18 2022-08-02 安斯泰来制药株式会社 含有抗人tslp受体抗体的药物组合物
JP7208302B2 (ja) 2015-12-18 2023-01-18 アップストリーム バイオ インコーポレイテッド 抗ヒトｔｓｌｐ受容体抗体含有医薬組成物
CN108430507A (zh) * 2015-12-18 2018-08-21 安斯泰来制药株式会社 含有抗人tslp受体抗体的药物组合物
WO2017104778A1 (ja) * 2015-12-18 2017-06-22 アステラス製薬株式会社 抗ヒトｔｓｌｐ受容体抗体含有医薬組成物
US12168697B2 (en) 2015-12-25 2024-12-17 Chugai Seiyaku Kabushiki Kaisha Bispecific antibodies which bind blood coagulation factor VIII and have enhanced activity, and methods of use thereof for treating bleeding and associated conditions
US11649262B2 (en) 2015-12-28 2023-05-16 Chugai Seiyaku Kabushiki Kaisha Method for promoting efficiency of purification of Fc region-containing polypeptide
US11071782B2 (en) 2016-04-20 2021-07-27 Coherus Biosciences, Inc. Method of filling a container with no headspace
US11576971B2 (en) 2016-04-20 2023-02-14 Coherus Biosciences, Inc. Method of filling a container with no headspace
JP2023145766A (ja) * 2016-04-28 2023-10-11 中外製薬株式会社 抗体含有製剤
JP2022037069A (ja) * 2016-04-28 2022-03-08 中外製薬株式会社 抗体含有製剤
US12460014B2 (en) 2016-04-28 2025-11-04 Chugai Seiyaku Kabushiki Kaisha Antibody-containing preparation
JP7320943B2 (ja) 2016-04-28 2023-08-04 中外製薬株式会社 抗体含有製剤
JPWO2017188356A1 (ja) * 2016-04-28 2019-03-07 中外製薬株式会社 抗体含有製剤
WO2017188356A1 (ja) * 2016-04-28 2017-11-02 中外製薬株式会社 抗体含有製剤
JP7544932B2 (ja) 2016-04-28 2024-09-03 中外製薬株式会社 抗体含有製剤
US12545743B2 (en) 2016-07-29 2026-02-10 Chugai Seiyaku Kabushiki Kaisha Bispecific antibody exhibiting increased alternative FVIII-cofactor-function activity
US11352438B2 (en) 2016-09-06 2022-06-07 Chugai Seiyaku Kabushiki Kaisha Methods of using a bispecific antibody that recognizes coagulation factor IX and/or activated coagulation factor IX and coagulation factor X and/or activated coagulation factor X
JP2024178197A (ja) * 2016-09-27 2024-12-24 フレゼニウス カービ ドイチュラント ゲーエムベーハー 液体医薬組成物
WO2018060210A1 (en) 2016-09-27 2018-04-05 Ares Trading S.A. Liquid pharmaceutical composition
EP3964197A1 (en) 2016-10-31 2022-03-09 Fresenius Kabi Deutschland GmbH Liquid pharmaceutical composition
WO2018078162A1 (en) 2016-10-31 2018-05-03 Ares Trading S.A. Liquid pharmaceutical composition
JPWO2018179138A1 (ja) * 2017-03-29 2020-02-06 持田製薬株式会社 抗体含有液体製剤
WO2018179138A1 (ja) * 2017-03-29 2018-10-04 持田製薬株式会社 抗体含有液体製剤
US12600798B2 (en) 2017-03-31 2026-04-14 Public University Corporation Nara Medical University Medicinal composition usable for preventing and/or treating blood coagulation factor IX abnormality, comprising multispecific antigen binding molecule replacing function of blood coagulation factor VIII
US11845798B2 (en) 2017-05-02 2023-12-19 Merck Sharp & Dohme Llc Formulations of anti-LAG3 antibodies and co-formulations of anti-LAG3 antibodies and anti-PD-1 antibodies
US10759870B2 (en) 2017-09-29 2020-09-01 Chugai Seiyaku Kabushiki Kaisha Multispecific antigen-binding molecules having blood coagulation factor VIII (FVIII) cofactor function-substituting activity and pharmaceutical formulations containing such a molecule as an active ingredient
US12522668B2 (en) 2017-09-29 2026-01-13 Chugai Seiyaku Kabushiki Kaisha Multispecific antigen-binding molecules having blood coagulation factor VIII (FVIII) cofactor function-substituting activity and pharmaceutical formulations containing such a molecule as an active ingredient
US12421322B2 (en) 2017-11-01 2025-09-23 Chugai Seiyaku Kabushiki Kaisha Antibody variant and isoform with lowered biological activity
WO2020056008A1 (en) 2018-09-12 2020-03-19 Silverback Therapeutics, Inc. Compositions for the treatment of disease with immune stimulatory conjugates
US12565526B2 (en) 2018-10-18 2026-03-03 Merck Sharpe & Dohme LLC Formulations of anti-RSV antibodies and methods of use thereof
US12576159B2 (en) 2018-10-31 2026-03-17 Merck Sharp & Dohme Llc Anti-human PD-1 antibody crystals and methods of use thereof
US12319735B2 (en) 2018-11-07 2025-06-03 Merck Sharp & Dohme Llc Co-formulations of anti-LAG3 antibodies and anti-PD-1 antibodies
WO2020185750A1 (en) * 2019-03-11 2020-09-17 Biogen Ma Inc. Pharmaceutical compositions containing anti-lingo-1 antibodies
JP2022524814A (ja) * 2019-03-11 2022-05-10 バイオジェン・エムエイ・インコーポレイテッド 抗ｌｉｎｇｏ－１抗体を含む医薬組成物
CN113661179A (zh) * 2019-03-11 2021-11-16 比奥根Ma公司 含有抗lingo-1抗体的药物组合物
WO2020257407A1 (en) 2019-06-19 2020-12-24 Silverback Therapeutics, Inc. Anti-mesothelin antibodies and immunoconjugates thereof
US12364768B2 (en) 2020-02-21 2025-07-22 Araris Biotech Ag Nectin-4 antibody conjugates and uses thereof
US11179473B2 (en) 2020-02-21 2021-11-23 Silverback Therapeutics, Inc. Nectin-4 antibody conjugates and uses thereof
JP2023532326A (ja) * 2020-06-29 2023-07-27 ハナル バイオファーマ カンパニーリミテッド 抗ｆｃｒｎ抗体のための製剤
US11541126B1 (en) 2020-07-01 2023-01-03 Silverback Therapeutics, Inc. Anti-ASGR1 antibody TLR8 agonist comprising conjugates and uses thereof
JP7558320B2 (ja) 2022-03-02 2024-09-30 ノヴォ・ノルディスク・ヘルス・ケア・アーゲー Ｆｖｉｉｉ模倣二重特異性抗体を週１回投与する方法
JP7558321B2 (ja) 2022-03-02 2024-09-30 ノヴォ・ノルディスク・ヘルス・ケア・アーゲー Ｆｖｉｉｉ模倣二重特異性抗体を２週ごとに投与する方法
JP7558322B2 (ja) 2022-03-02 2024-09-30 ノヴォ・ノルディスク・ヘルス・ケア・アーゲー Ｆｖｉｉｉ模倣二重特異性抗体を月１回投与する方法
JP2023135622A (ja) * 2022-03-02 2023-09-28 ノヴォ・ノルディスク・ヘルス・ケア・アーゲー Ｆｖｉｉｉ模倣二重特異性抗体を月１回投与する方法
JP2023129759A (ja) * 2022-03-02 2023-09-19 ノヴォ・ノルディスク・ヘルス・ケア・アーゲー Ｆｖｉｉｉ模倣二重特異性抗体を２週ごとに投与する方法
JP2023129758A (ja) * 2022-03-02 2023-09-19 ノヴォ・ノルディスク・ヘルス・ケア・アーゲー Ｆｖｉｉｉ模倣二重特異性抗体を週１回投与する方法
US12150991B2 (en) 2022-11-07 2024-11-26 Upstream Bio, Inc. Pharmaceutical compositions comprising anti-human TSLP receptor antibodies and methods of using the same
JP7739537B2 (ja) 2023-06-23 2025-09-16 ノヴォ・ノルディスク・ヘルス・ケア・アーゲー Ｆｖｉｉｉ模倣二重特異性抗体を２ヶ月に１回投与する方法
JP2025003418A (ja) * 2023-06-23 2025-01-09 ノヴォ・ノルディスク・ヘルス・ケア・アーゲー Ｆｖｉｉｉ模倣二重特異性抗体を２ヶ月に１回投与する方法

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