WO2003068259A1 - Antibody-containing solution pharmaceuticals - Google Patents
Antibody-containing solution pharmaceuticals Download PDFInfo
- Publication number
- WO2003068259A1 WO2003068259A1 PCT/JP2003/001562 JP0301562W WO03068259A1 WO 2003068259 A1 WO2003068259 A1 WO 2003068259A1 JP 0301562 W JP0301562 W JP 0301562W WO 03068259 A1 WO03068259 A1 WO 03068259A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- antibody
- solution
- solution preparation
- preparation according
- insoluble
- Prior art date
Links
Classifications
-
- 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
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/34—Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/44—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material not provided for elsewhere, e.g. haptens, metals, DNA, RNA, amino acids
-
- 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
- A61K39/39591—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
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
-
- 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
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/12—Carboxylic acids; Salts or anhydrides thereof
-
- 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
- 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
-
- 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
- A61K9/08—Solutions
-
- 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
- A61P37/04—Immunostimulants
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/30—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
- C07K16/3061—Blood cells
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/40—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against enzymes
-
- 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
Definitions
- the present invention relates to a stable antibody-containing solution formulation.
- anti-HM1.24 antibody has a therapeutic effect on myeloma cells (Japanese Patent Publication No. 1 1-0 9 2 3 9 9), and has studied the formulation of this antibody. .
- Anti-HM1.24 antibody is an unstable protein. Physical and chemical changes such as aggregation and aggregation due to filtration stress, concentration stress, heat stress, and light stress for virus removal and sterilization performed in the purification process. It is easy to produce.
- antibody-producing cells are cultured in Balta, and the antibody-containing solution obtained by purification is stored frozen and thawed at the formulation stage.
- antibody aggregates and insoluble fine particles are generated, and the antibody is decomposed during long-term storage, resulting in degradation products, resulting in a decrease in the residual ratio of the antibody. Met.
- proteins such as human serum albumin or purified gelatin and polymers, or polyols, amino acids and surfactants are used. Stabilizing effects have been found by adding low molecular weights.
- a biological polymer such as a protein as a stabilizer has a problem that a very complicated process is required for removing contaminants such as viruses and prions.
- the object of the present invention is to suppress the formation of insoluble foreign matter and insoluble fine particles due to physical stress such as freezing and thawing in the process of producing an antibody-containing solution preparation and antibody aggregation during long-term storage. It is intended to provide an antibody-containing solution preparation that is stable for long-term storage and suppresses the formation of insoluble foreign matter and fine particles caused by metal ions (Fe ions) mixed in the body.
- metal ions Fe ions
- the present inventors have been able to remarkably suppress the formation of insoluble foreign matter during the addition of iron by using an organic acid, and by adding a surface active agent.
- the present invention was completed by discovering that generation of insoluble foreign matter and insoluble ⁇ raw fine particles at the stage of freezing and thawing can be remarkably suppressed.
- the present invention provides the following.
- An antibody-containing solution preparation containing an organic acid and a surfactant as a stabilizer.
- An anti-HM1.24 antibody-containing solution formulation comprising 10-5 OmM acetic acid and 0.01-1 OmgZmL polysorbate 80 as a stabilizer.
- a method for suppressing the formation of insoluble foreign matter and insoluble fine particles caused by metal ions in an antibody-containing solution preparation comprising adding an organic acid to the solution.
- a method for suppressing the formation of insoluble foreign matter and insoluble fine particles during shaking and freezing and thawing of an antibody-containing solution which comprises adding a surfactant to the solution.
- the antibody-containing solution preparation refers to a solution preparation prepared so as to contain an antibody as an active ingredient and can be administered to an animal such as a human, and is preferably produced without a freeze-drying step in the production process.
- Solution formulation a solution preparation prepared so as to contain an antibody as an active ingredient and can be administered to an animal such as a human, and is preferably produced without a freeze-drying step in the production process.
- the antibody-containing solution may be a solution containing any antibody, regardless of whether it is a biologically derived antibody or a recombinant antibody.
- an antibody obtained by culturing is used.
- mammalian cell culture media such as CHO cells, or those that have been subjected to certain treatments such as partial purification (Parc solution), or solutions prepared so that they can be administered to animals such as the above-mentioned humans It is a formulation.
- the insoluble fine particles are fine insoluble foreign matters having a size of 10 m or more as defined in the Japanese Pharmacopoeia, General Test Methods, Insoluble Fine Particle Test Methods for Injections. Insoluble fine particles are measured using a microscope, a filter for collecting insoluble fine particles, and a membrane filter for measurement, but can be measured simply by using a light shielding or automatic fine particle measuring apparatus.
- insoluble foreign matter means that the solution described in the European Pharmacopoeia, 3rd edition, 2.9.20 is applied mutatis mutandis, and the solution preparation contained in the container is about 3 under a black light source directly under a white light source. It is an insoluble 1 "foreign matter that is easily detected when observing with the naked eye at a brightness level of 0 0 0 lux (2 0 0 0 to 3 7 5 0 noretas).
- the aggregates and degradation products refer to the aggregates and degradation products of antibody molecules that are active ingredients of the preparation, respectively, and the contents can be determined by, for example, an area percentage method using gel filtration chromatography described later. .
- the antibody used in the solution preparation of the present invention is not particularly limited as long as it binds to a desired antigen, and mouse antibody, rat antibody, rabbit antibody, Hedge antibody, chimeric antibody, humanized antibody, human antibody, etc. are appropriately used. be able to.
- the antibody may be a polyclonal antibody or a monoclonal antibody, but a monoclonal antibody is preferable in that it can stably produce a homogeneous antibody.
- Polyclonal antibodies and monoclonal antibodies can be prepared by methods well known to those skilled in the art.
- a hybridoma producing a monoclonal antibody can be basically produced using a known technique as follows. That is, a desired antigen or a cell that expresses a desired antigen is used as a sensitizing antigen, and this is immunized according to a normal immunization method. The resulting immune cell is combined with a known parent cell by a normal cell fusion method. It can be prepared by fusing and screening monoclonal antibody-producing cells (hybridomas) by conventional screening methods. Hypridoma can be prepared according to, for example, 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, it may be immunized by binding to an immunogenic macromolecule such as alpmin.
- an immunogenic macromolecule such as alpmin.
- an antibody gene is cloned from a hybridoma, incorporated into an appropriate vector, introduced into a host, and produced using genetic recombination technology.
- Recombinant antibodies can be used (see, eg, Carl, AK Borrebaeck, James, W. Larrick, THERAPEUTIC MONOCLONAL ANTIBODIES, Published in the United Kingdom by MACMILLAN PUBLISHERS LTD, 1990).
- cDNA for the variable region (V region) of the antibody is synthesized from the mRNA of the hyperidoma using reverse transcriptase.
- DNA encoding the V region of the desired antibody is obtained, it is ligated with DNA encoding the desired antibody constant region (C region) and incorporated into an expression vector.
- DNA encoding an antibody V region may be incorporated into an expression vector containing antibody C region DNA. It is incorporated into an expression vector so that it is 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 artificially modified for the purpose of reducing the heterologous antigenicity to humans for example, a chimeric antibody, a humanized antibody, or the like can be used.
- modified antibodies can be produced using known methods.
- a chimeric antibody is an antibody consisting of a mammalian antibody other than human, for example, the heavy chain of a mouse antibody, the variable region of a light chain, the heavy chain of a human antibody, and the constant region of a light chain, and encodes the variable region of a mouse antibody.
- This DNA can be obtained by ligating the DNA to be encoded with DNA encoding the constant region of a human antibody, incorporating it into an expression vector, introducing it into a host, and producing it.
- Humanized antibodies are also called reshaped human antibodies, and non-human mammals, such as the complementarity determining regions (CDRs) of mouse antibodies, are transplanted into the complementarity determining regions of human antibodies.
- CDRs complementarity determining regions
- the general genetic recombination technique is also known. Specifically, several DNA sequences designed to link mouse antibody CDRs and human antibody framework regions (FR) with overlapping portions at the ends are prepared. It is synthesized by PCR from the above oligonucleotides. The obtained DNA is obtained by linking with the DNA encoding the constant region of the human antibody, then incorporating it into an expression vector, introducing it into a host and producing it (European Patent Application Publication No. EP 239400, International Patent Application Publication) No. WO 96/02576).
- the FR is selected such that the complementarity determining region forms a good antigen binding site. 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 in vitro with a desired antigen or a cell that expresses the desired antigen, and the sensitized lymphocytes are fused with human myeloma cells such as U266, and the desired human antibody having an antigen-binding activity.
- Can also be obtained see Japanese Patent Publication 1-59878.
- 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 can be expressed as a single-chain antibody (scFv) on the surface of the phage by the phage display method, and the 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, an appropriate expression vector can be prepared from the sequence 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 African megal oocytes, or (3) insects Cells such as sf9, sf21, and Tn5 are known.
- plant cells cells derived from the genus Nicotiana, for example, Nicotiana tabacum, are known and can be cultured in callus.
- fungal cells examples include yeast, for example, the genus Saccharomyces, For example, Saccharomyces serevisiae, filamentous fungi, such as the genus Aspergillus, such as Aspergillus niger, are known.
- yeast for example, the genus Saccharomyces
- filamentous fungi such as the genus Aspergillus, such as Aspergillus niger
- prokaryotic cells there are production systems that use bacterial cells.
- Known bacterial cells include E. coli 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.
- Examples of the antibody contained in the stabilized preparation of the present invention include anti-IL-16 receptor antibody, anti-HM1.24 antigen monoclonal antibody, anti-parathyroid hormone related peptide antibody (anti-PTHr P antibody) and the like. It is not limited to this.
- Examples of the reshaped humanized antibody include a humanized anti-IL-16 receptor antibody (hPM-1) (see International Patent Application Publication No. WO 92-19759), a humanized anti-HM1.24 antigen monoclonal antibody (International patent application publication number WO 98-14580), human type anti-parathyroid hormone related peptide antibody (anti-PTHr P antibody) (see international patent application publication number WO 98-13388), etc. It is mentioned as a preferable antibody to be used.
- the immunoglobulin class of the antibody contained in the solution preparation of the present invention is not limited. Ig G such as II g G 1, I g G 2, I g G 3, and I g G 4 is preferred, and I g G 1 Is more preferable.
- the formation of insoluble foreign matter and insoluble fine particles due to metal ions (Fe ions) mixed during the production process can be remarkably suppressed by adding an organic acid.
- organic acid acetic acid and citrate are preferable, and acetic acid is more preferable. A mixture of these can also be used.
- the organic acid can be added by dissolving the antibody and other components in an organic acid buffer.
- a solution formulation is prepared by dissolving antibodies and other components in an aqueous buffer known in the field of solution formulations such as acetate buffer and / or taenoate buffer (preferably sodium citrate buffer). .
- the concentration of the buffer is generally 1 to 500 mM, preferably 5 to 100 mM, and more preferably 10 to 5 OmM.
- the antibody-containing solution preparation of the present invention is obtained by adding an organic acid to room temperature (25 ° C). Under storage, when iron ions were contained, the formation of insoluble foreign matter could be remarkably suppressed as compared with the antibody-containing solution preparation added with an inorganic acid.
- surface active agents include nonionic surfactants such as sorbitan fatty acid esters such as sorbitan monocaprylate, sorbitan monolaurate, and sorbitan monopalmitate; glycerin monocaprylate, glycerin monomilitate, glycerin mono Glycerin fatty acid esters such as stearate; polyglycerin fatty acid esters such as decaglyceryl monostearate, decaglyceryl distearate, decaglyceryl monolinoleate; polyoxyethylene sorbitan monolaurate, polyoxyethylene sorbitan monooleate, polyoxyethylate Polyoxyethylene sorbitan trioleate, polyoxyethylene sorbitan fatty acid ester such as polyoxyethylene sorbitan tristearate;
- nonionic surfactants such as sorbitan fatty acid esters such as sorbitan monocaprylate, sorbitan monolaurate, and sorbitan monopalmitate;
- surfactants can be added to the preparation of the present invention in combination.
- Preferred surfactants for use in the solution formulations of the present invention are polyoxyethylene sorbitan fatty acid esters such as polysorbate 20, 40, 60 or 80, with polysorbates 20 and 80 being particularly preferred.
- polyoxyethylene polyoxypropylene dalicol represented by poloxamer such as Pull Knick F-68 (registered trademark)
- Poloxamer 188 is particularly preferred.
- the amount of surfactant added depends on the type of surfactant used, but in the case of polysorbate 20 or poloxamer 188, it is generally 0.001 to: LO Omg / mL (0.0001 to 10%). Yes, preferably 0.005 to 50 mg / mL (0.0005 to 5%), and more preferably 0.01 to 10 mgZmL (0.001 to 1%). More preferably, the number of insoluble fine particles of 25 ⁇ m or more is suppressed to 3 or less even after a single freeze-thaw at 200 ° C / min x 30 min and once at 80 ° C and 25 ° C. Possible is 0.025 to 0.25 mg / mL (0.0025 to 0.025%).
- polysorbate 80 0.001 to: 10 Omg / mL (0.0001 to 10%), preferably 0.005 to 50 mg / mL (0.0005 to 5%), more preferably 0.01 to 10 mg / mL (0.001 to 1%). More preferably, the insoluble fine particles of 25 ⁇ or more can be suppressed to 0 even after repeating the shaking 200 times / min ⁇ 60 minutes and freeze-thawing at 20 ° C. and 5 ° C. three times. The formation of foreign matter is not observed, and is 0.025 to lmg / mL (0.0025 to 0.1%).
- the antibody-containing solution preparation of the present invention is preferably substantially free of proteins such as human serum alpmin and purified gelatin as a stabilizer.
- Sodium chloride can be further added to the antibody-containing solution preparation of the present invention.
- the amount of sodium chloride added is 10 to 30 O mM, preferably 20 to 20 O mM.
- the pH of the antibody-containing solution preparation of the present invention is preferably pH 4 to 8, more preferably pH 5 to 7.5.
- pH differs depending on the antibody contained, and is not limited thereto.
- the antibody when the antibody is an anti-HM1.24 antibody, it suppresses the formation of aggregates after heat stress, keeps the residual rate high, and also suppresses the generation of charged heteromolecules (deamides, etc.). Is most preferably ⁇ ⁇ 5.5 to 6.5.
- the preferred pH for each antibody can be determined by a method according to the examples described later.
- saccharides such as mannose and sorbitol
- non-reducing disaccharides such as sucrose and trehalose
- non-reducing oligosaccharides such as raffinose and other non-reducing trisaccharides
- saccharides such as polyethylene glycol, dextrane, mannitol, sorbitol, inositol, glucose, fructose, ratatose, xylose, mannose, manoletose, sucrose, toreno, rosin, and raffinose are further added as isotonic agents. Can be used.
- the antibody-containing solution preparation of the present invention further contains a diluent, a solubilizing agent, an excipient, a pH adjusting agent, a soothing agent, a buffering agent, a sulfur-containing reducing agent, an antioxidant and the like as desired.
- sulfur-containing reducing agents include ⁇ -acetyl cysteine, ⁇ -acetyl cysteine, thioctic acid, thiodidalol, thioethanolamine, thioglycerol, thiosorbitol, thioglycolic acid and its salts, sodium thiosulfate, and glutathione.
- Anti-oxidant agents include erythorbic acid, dibutinoreoxy droxytonolene, petitnoreoxy doxyaniso / re, one-tocopherol, tocopherol acetate, L-ascorbic acid and its salts, L-ascorbyl palmitate, L-ascorbic acid stearate. Rate, sodium bisulfite, sulfurous acid Chelating agents such as sodium oxalate, triamyl gallate, propyl gallate or disodium ethylenediaminetetraacetate (EDTA), sodium pyrophosphate, sodium metaphosphate.
- EDTA disodium ethylenediaminetetraacetate
- inorganic salts such as sodium chloride, potassium chloride, calcium chloride, sodium phosphate, potassium phosphate, and sodium hydrogen carbonate; organic salts such as sodium citrate, potassium citrate, and sodium acetate are usually added. Ingredients may be included.
- the antibody-containing solution preparation of the present invention is usually administered by parenteral administration route, for example, injection (subcutaneous injection, intravenous injection, intramuscular injection, intraperitoneal injection, etc.), transdermal, transmucosal, nasal, entangled lung, etc.
- parenteral administration route for example, injection (subcutaneous injection, intravenous injection, intramuscular injection, intraperitoneal injection, etc.), transdermal, transmucosal, nasal, entangled lung, etc.
- parenteral administration route for example, injection (subcutaneous injection, intravenous injection, intramuscular injection, intraperitoneal injection, etc.), transdermal, transmucosal, nasal, entangled lung, etc.
- parenteral administration route for example, injection (subcutaneous injection, intravenous injection, intramuscular injection, intraperitoneal injection, etc.), transdermal, transmucosal, nasal, entangled lung, etc.
- oral administration is also possible.
- the antibody-containing solution preparation of the present invention is usually supplied in a container with a predetermined volume shape such as a sealed, sterilized plastic or glass vial, ampoule or syringe, and a container with a large volume shape such as a bottle. Can do. From the viewpoint of convenience of use, a prefilled syringe is preferable.
- the amount of the antibody contained in the preparation of the present invention can be determined according to the type of disease to be treated, the severity of the disease, the age of the patient, etc., but generally 0.1 to 200 mg Zml, preferably It is preferably 1 to 12 O mg / m 1.
- the antibody-containing solution preparation of the present invention remarkably suppresses the generation of insoluble foreign matters when iron is added by adding an organic acid, particularly acetic acid or quenic acid, to the antibody solution, as shown in the examples described later. It was done. Therefore, by adding an organic acid, it is possible to suppress the formation of insoluble foreign matter and fine particles caused by metal ions (Fe ions) mixed during the production process. Furthermore, the antibody-containing solution preparation of the present invention was able to significantly suppress the formation of insoluble foreign matter and insoluble fine particles due to freezing and thawing by adding a surfactant.
- an organic acid particularly acetic acid or quenic acid
- Antibody sample An antibody prepared according to the method described in Reference Example 2 of International Patent Application Publication No. WO 98-35698 as a humanized anti-HM1.24 antigen monoclonal antibody (hereinafter referred to as anti-HM1.24 antibody) was used.
- the anti-HM1.24 antibody used in this example is an Ig G 1 class antibody.
- the residual rate (%) relative to the initial product was used as an index. Aggregates and degradation products are shown as percentages.
- Isolates charged heteromolecules caused by degradation such as antibody deamidation.
- the increase or decrease of the main peak was used as an indicator of stability.
- Mobile phase Use the following liquid A and liquid B, and perform a dual-liquid mixture.
- Solution A 25 mM MES buffer with pH 6.1 (0.05% sodium azide)
- Solution B 250 mM sodium chloride at pH 6.1 ⁇ 25 mM MES buffer (0.05% sodium azide)
- the peak area of the chromatogram obtained by HPLC was measured by the automatic integration method, and the ratio (%) of the main peak was determined by the area percentage method.
- Measuring method JP's general test method ⁇ Insoluble particle test method for injections ⁇ Light shielding type automatic particle measurement device
- Measuring equipment Light shielding type automatic particle measuring equipment (HIAC) (4) Insoluble foreign matter test
- insoluble foreign matter test method the formation of insoluble foreign matter when iron (FeCl 3 ) is added to anti-HM1.24 antibody preparations that differ only in the buffer components (phosphate, acetic acid, citrate) under the black background visually confirmed.
- the sample was stored at room temperature (about 25 ° C).
- Table 1 shows the prescriptions to be studied, and Table 2 shows the results.
- Evaluation sample 2mL filling / 5mL trial (Samplel3 ⁇ Sample22)
- Evaluation sample 10mL filling / 20mL trial (Sample23 ⁇ Sample28)
- Evaluation sample 10mL filling / 20mL trial (Sample 39 ⁇ Sample 42)
- Evaluation method Insoluble foreign matter test using EP method (under black background)
- Table 7 shows the prescriptions to be studied
- Table 8 shows the results.
- Evaluation sample lmL filling / 5mL trial (Sample 43 to Sample 47)
- Table 9 shows the prescriptions to be studied
- Table 10 shows the results.
- Evaluation sample lmL filled / 5mL vial (Sample 48 to Sample 54) Evaluation method: Thermal severe test
- Table 11 shows the study recipe
- Table 12 shows the results.
- Polysorbate80 (%) 0.05 0.05 0.05 Acetate buffer (mM) 10 10 10 10 pH 6.0 6.0 6.0
- Evaluation sample lmL filling / 5mL trial (Sample 59,62,63)
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Immunology (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Engineering & Computer Science (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biophysics (AREA)
- Genetics & Genomics (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Cell Biology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Mycology (AREA)
- Microbiology (AREA)
- Hematology (AREA)
- Dermatology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Inorganic Chemistry (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Medicinal Preparation (AREA)
- Peptides Or Proteins (AREA)
Description
Claims
Priority Applications (6)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US10/504,025 US20050118163A1 (en) | 2002-02-14 | 2003-02-14 | Antibody-containing solution pharmaceuticals |
EP20030705165 EP1475100B1 (en) | 2002-02-14 | 2003-02-14 | Use of acetic acid for suppressing Fe ion induced problems in formulations of anti-HM1.24 or anti-IL6R antibodies |
ES03705165.3T ES2536709T3 (es) | 2002-02-14 | 2003-02-14 | Utilización de ácido acético para eliminar los problemas inducidos por el ión Fe en las formulaciones de anticuerpos anti-HM1.24 o anti-IL6R |
JP2003567439A JP4364645B2 (ja) | 2002-02-14 | 2003-02-14 | 抗体含有溶液製剤 |
AU2003211990A AU2003211990A1 (en) | 2002-02-14 | 2003-02-14 | Antibody-containing solution pharmaceuticals |
US12/184,551 US8921527B2 (en) | 2002-02-14 | 2008-08-01 | Antibody-containing solution formulations |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2002036244 | 2002-02-14 | ||
JP2002-36244 | 2002-02-14 |
Related Child Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US10504025 A-371-Of-International | 2003-02-14 | ||
US12/184,551 Division US8921527B2 (en) | 2002-02-14 | 2008-08-01 | Antibody-containing solution formulations |
Publications (1)
Publication Number | Publication Date |
---|---|
WO2003068259A1 true WO2003068259A1 (en) | 2003-08-21 |
Family
ID=27678080
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/JP2003/001563 WO2003068260A1 (en) | 2002-02-14 | 2003-02-14 | Antibody-containing solution pharmaceuticals |
PCT/JP2003/001562 WO2003068259A1 (en) | 2002-02-14 | 2003-02-14 | Antibody-containing solution pharmaceuticals |
Family Applications Before (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/JP2003/001563 WO2003068260A1 (en) | 2002-02-14 | 2003-02-14 | Antibody-containing solution pharmaceuticals |
Country Status (25)
Country | Link |
---|---|
US (4) | US20050118163A1 (ja) |
EP (5) | EP3192528A1 (ja) |
JP (4) | JP4364645B2 (ja) |
KR (3) | KR101080021B1 (ja) |
CN (3) | CN101066450A (ja) |
AT (1) | ATE485835T1 (ja) |
AU (3) | AU2003211991B2 (ja) |
BR (1) | BRPI0307702B8 (ja) |
CA (1) | CA2474943C (ja) |
CO (1) | CO5611163A2 (ja) |
CY (2) | CY1111073T1 (ja) |
DE (1) | DE60334678D1 (ja) |
DK (1) | DK1475101T3 (ja) |
ES (2) | ES2353496T3 (ja) |
HR (1) | HRP20040710B1 (ja) |
IL (1) | IL163354A (ja) |
MX (1) | MXPA04007924A (ja) |
NO (1) | NO333553B1 (ja) |
NZ (1) | NZ534542A (ja) |
PL (1) | PL213311B1 (ja) |
PT (1) | PT1475101E (ja) |
RU (1) | RU2335299C2 (ja) |
SI (1) | SI1475101T1 (ja) |
WO (2) | WO2003068260A1 (ja) |
ZA (1) | ZA200406230B (ja) |
Cited By (20)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
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 |
WO2007074880A1 (ja) * | 2005-12-28 | 2007-07-05 | Chugai Seiyaku Kabushiki Kaisha | 抗体含有安定化製剤 |
EP1592440A4 (en) * | 2003-02-10 | 2007-07-11 | Elan Pharm Inc | IMMUNOGLOBULIN PREPARATION AND METHOD OF PRODUCING THE SAME |
JP2008540684A (ja) * | 2005-05-19 | 2008-11-20 | アムジェン インコーポレイテッド | 抗体の安定性を増加させるための組成物および方法 |
WO2010106812A1 (en) * | 2009-03-19 | 2010-09-23 | Chugai Seiyaku Kabushiki Kaisha | Pharmaceutical formulation containing improved antibody molecules |
US8562991B2 (en) | 2008-09-26 | 2013-10-22 | Chugai Seiyaku Kabushiki Kaisha | Antibody molecules that bind to IL-6 receptor |
US8568720B2 (en) | 2007-12-27 | 2013-10-29 | Chugai Seiyaku Kabushiki Kaisha | High concentration antibody-containing liquid formulation |
US8840884B2 (en) | 2002-02-14 | 2014-09-23 | Chugai Seiyaku Kabushiki Kaisha | Antibody-containing solution pharmaceuticals |
EP1698640B1 (en) | 2003-10-01 | 2015-12-30 | Kyowa Hakko Kirin Co., Ltd. | Method of stabilizing antibody and stabilized solution-type antibody preparation |
US9592297B2 (en) | 2012-08-31 | 2017-03-14 | Bayer Healthcare Llc | Antibody and protein formulations |
JP2017071631A (ja) * | 2010-09-17 | 2017-04-13 | バクスアルタ ゲーエムベーハー | 弱酸性〜中性のpHにおける、ヒスチジンを有する水性製剤を介した免疫グロブリンの安定化 |
US9795674B2 (en) | 2010-02-26 | 2017-10-24 | Novo Nordisk A/S | Stable antibody containing compositions |
CN108025033A (zh) * | 2015-09-11 | 2018-05-11 | 陶氏环球技术有限责任公司 | 包含蛋白质和聚烷氧基脂肪族化合物的组合物 |
US10022319B2 (en) | 2010-01-20 | 2018-07-17 | Chugai Seiyaku Kabushiki Kaisha | Stabilized antibody-containing liquid formulations |
USRE47150E1 (en) | 2010-03-01 | 2018-12-04 | Bayer Healthcare Llc | Optimized monoclonal antibodies against tissue factor pathway inhibitor (TFPI) |
US10744201B2 (en) | 2003-04-28 | 2020-08-18 | Chugai Seiyaku Kabushiki Kaisha | Method for treating rheumatoid arthritis with a human IL-6 receptor antibody and methotrexate |
US10774148B2 (en) | 2015-02-27 | 2020-09-15 | Chugai Seiyaku Kabushiki Kaisha | Composition for treating IL-6-related diseases |
US10835602B2 (en) | 2010-05-28 | 2020-11-17 | Novo Nordisk A/S | Stable multi-dose compositions comprising an antibody and a preservative |
US11021728B2 (en) | 2009-10-26 | 2021-06-01 | Hoffmann-La Roche Inc. | Method for the production of a glycosylated immunoglobulin |
US11851486B2 (en) | 2017-05-02 | 2023-12-26 | National Center Of Neurology And Psychiatry | Method for predicting and evaluating therapeutic effect in diseases related to IL-6 and neutrophils |
Families Citing this family (100)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
ES2312184T3 (es) | 1997-03-21 | 2009-02-16 | Chugai Seiyaku Kabushiki Kaisha | Agentes preventivos terapeuticos para el tratamiento de esclerosis multiple, que contienen anticuerpos anti-receptores de il-6 antagonistas. |
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 |
US8658773B2 (en) | 2011-05-02 | 2014-02-25 | Immunomedics, Inc. | Ultrafiltration concentration of allotype selected antibodies for small-volume administration |
US20160279239A1 (en) | 2011-05-02 | 2016-09-29 | Immunomedics, Inc. | Subcutaneous administration of anti-cd74 antibody for systemic lupus erythematosus and autoimmune disease |
US20040033228A1 (en) | 2002-08-16 | 2004-02-19 | Hans-Juergen Krause | Formulation of human antibodies for treating TNF-alpha associated disorders |
AU2003262087B2 (en) | 2002-09-11 | 2010-11-11 | Chugai Seiyaku Kabushiki Kaisha | Protein purification method |
AU2003271175A1 (en) * | 2002-10-11 | 2004-05-04 | Masahiro Abe | Cell death-inducing agent |
MY150740A (en) * | 2002-10-24 | 2014-02-28 | Abbvie Biotechnology Ltd | Low dose methods for treating disorders in which tnf? activity is detrimental |
JP4607010B2 (ja) * | 2003-02-28 | 2011-01-05 | 中外製薬株式会社 | タンパク質含有安定化製剤 |
TW200530269A (en) * | 2003-12-12 | 2005-09-16 | Chugai Pharmaceutical Co Ltd | Anti-Mpl antibodies |
EP1710255A4 (en) * | 2003-12-12 | 2008-09-24 | Chugai Pharmaceutical Co Ltd | MODIFIED ANTIBODIES RECOGNIZING A TRIMER OR LARGER RECEPTOR |
JPWO2005056602A1 (ja) * | 2003-12-12 | 2008-03-06 | 中外製薬株式会社 | アゴニスト活性を有する改変抗体のスクリーニング方法 |
CA2548929A1 (en) * | 2003-12-12 | 2005-06-23 | Chugai Seiyaku Kabushiki Kaisha | Cell death inducing agent |
US8398980B2 (en) * | 2004-03-24 | 2013-03-19 | Chugai Seiyaku Kabushiki Kaisha | Subtypes of humanized antibody against interleuken-6 receptor |
WO2005100560A1 (ja) * | 2004-04-09 | 2005-10-27 | Chugai Seiyaku Kabushiki Kaisha | 細胞死誘導剤 |
JP2006045162A (ja) * | 2004-08-06 | 2006-02-16 | Takeda Chem Ind Ltd | 注射用ペプチド含有組成物 |
JO3000B1 (ar) | 2004-10-20 | 2016-09-05 | Genentech Inc | مركبات أجسام مضادة . |
US20160355591A1 (en) | 2011-05-02 | 2016-12-08 | Immunomedics, Inc. | Subcutaneous anti-hla-dr monoclonal antibody for treatment of hematologic malignancies |
US20090238820A1 (en) * | 2005-03-08 | 2009-09-24 | Allan Corey M | ANTI-MAdCAM ANTIBODY COMPOSITIONS |
WO2006106903A1 (ja) | 2005-03-31 | 2006-10-12 | Chugai Seiyaku Kabushiki Kaisha | sc(Fv)2構造異性体 |
EP1927367A4 (en) * | 2005-05-18 | 2009-08-12 | Univ Tokushima | NOVEL PHARMACEUTICAL AGENT BASED ON AN ANTI-HLA ANTIBODY |
AU2006256041B2 (en) * | 2005-06-10 | 2012-03-29 | Chugai Seiyaku Kabushiki Kaisha | Stabilizer for protein preparation comprising meglumine and use thereof |
US9241994B2 (en) | 2005-06-10 | 2016-01-26 | Chugai Seiyaku Kabushiki Kaisha | Pharmaceutical compositions containing sc(Fv)2 |
EP3673919A1 (en) * | 2005-06-14 | 2020-07-01 | Amgen Inc. | Self-buffering protein formulations |
AU2006259536A1 (en) * | 2005-06-15 | 2006-12-28 | Schering Corporation | Anti-IGF1R antibody formulations |
BRPI0615745A2 (pt) * | 2005-09-12 | 2011-05-24 | Novimmune Sa | formulação de anticorpo anti-cd3 |
CA2634547C (en) | 2005-12-20 | 2016-10-11 | Bristol-Myers Squibb Company | Stable ctla4 formulation for subcutaneous administration |
US9309316B2 (en) | 2005-12-20 | 2016-04-12 | Bristol-Myers Squibb Company | Stable subcutaneous protein formulations and uses thereof |
CA2642270A1 (en) * | 2006-02-15 | 2007-08-23 | Imclone Systems Incorporated | Antibody formulation |
US8080248B2 (en) | 2006-06-02 | 2011-12-20 | Regeneron Pharmaceuticals, Inc. | Method of treating rheumatoid arthritis with an IL-6R antibody |
MX2008014804A (es) | 2006-06-02 | 2009-01-27 | Regeneron Pharma | Anticuerpos de afinidad elevada a receptor de il-6 humano. |
CA2657385A1 (en) * | 2006-07-13 | 2008-01-17 | Naoki Kimura | Cell death inducer |
CL2008000719A1 (es) * | 2007-03-12 | 2008-09-05 | Univ Tokushima Chugai Seiyaku | Agente terapeutico para cancer resistente a agentes quimioterapeuticos que comprende un anticuerpo que reconoce hla de clase i como ingrediente activo; composicion farmaceutica que comprende dicho anticuerpo; y metodo para tratar cancer resistente a |
CA2681743A1 (en) * | 2007-03-22 | 2008-09-25 | Imclone Llc | Stable antibody formulations |
US8168760B2 (en) | 2007-03-29 | 2012-05-01 | Abbott Laboratories | Crystalline anti-human IL-12 antibodies |
EP2036577A1 (de) * | 2007-09-14 | 2009-03-18 | mivenion GmbH | Diagnostische Stoffe für die optische bildgebende Untersuchung auf der Basis von nanopartikulären Formulierungen |
RU2550271C2 (ru) * | 2007-09-14 | 2015-05-10 | Санофи Пастер Байолоджикс Ко. | Иммуногенная композиция для лечения или профилактики clostridium difficile, способ ее получения и способ индукции иммунного ответа к c. difficile |
NZ602498A (en) * | 2007-11-30 | 2014-08-29 | Abbvie Inc | Protein formulations and methods of making same |
US8883146B2 (en) | 2007-11-30 | 2014-11-11 | Abbvie Inc. | Protein formulations and methods of making same |
KR101676887B1 (ko) * | 2008-11-20 | 2016-11-16 | 제넨테크, 인크. | 치료 단백질 제형 |
NZ592644A (en) * | 2008-11-28 | 2013-09-27 | Abbott Lab | Stable antibody compositions and methods for stabilizing same |
FR2944448B1 (fr) * | 2008-12-23 | 2012-01-13 | Adocia | Composition pharmaceutique stable comprenant au moins un anticorps monodonal et au moins un polysacharide amphiphile comprenant des substituants derives d'alcools hydrofobes ou d'amines hydrophobes. |
CN102300584A (zh) | 2008-12-31 | 2011-12-28 | 雷文斯治疗公司 | 可注射的肉毒杆菌毒素制剂 |
NZ595694A (en) * | 2009-05-04 | 2013-09-27 | Abbvie Biotechnology Ltd | Stable high protein concentration formulations of human anti-tnf-alpha-antibodies |
MX366344B (es) | 2009-06-25 | 2019-07-05 | Revance Therapeutics Inc | Formulaciones de toxina botulinica libres de albumina. |
NZ713967A (en) | 2009-07-28 | 2017-01-27 | Shire Human Genetic Therapies | Compositions and methods for treating gaucher disease |
US9345661B2 (en) | 2009-07-31 | 2016-05-24 | Genentech, Inc. | Subcutaneous anti-HER2 antibody formulations and uses thereof |
US8221753B2 (en) | 2009-09-30 | 2012-07-17 | Tracon Pharmaceuticals, Inc. | Endoglin antibodies |
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. |
SG10201408505SA (en) * | 2009-12-22 | 2015-02-27 | Celldex Therapeutics Inc | Vaccine compositions |
FR2958646B1 (fr) * | 2010-04-07 | 2012-05-18 | Adocia | Polysaccharides comportant des groupes fonctionnels carboxyles substitues par un derive d'acide hydrophobe. |
JO3417B1 (ar) | 2010-01-08 | 2019-10-20 | Regeneron Pharma | الصيغ المستقرة التي تحتوي على الأجسام المضادة لمضاد مستقبل( interleukin-6 (il-6r |
NZ602685A (en) * | 2010-03-01 | 2014-10-31 | Cytodyn Inc | Concentrated protein formulations and uses thereof |
CN103108658B (zh) * | 2010-07-02 | 2015-08-19 | 米迪缪尼有限公司 | 抗体制剂 |
CN102375056A (zh) * | 2010-08-27 | 2012-03-14 | 烟台赛尔斯生物技术有限公司 | 固定生物大分子的稳定剂及其制备方法和应用 |
CN103476793A (zh) | 2010-11-08 | 2013-12-25 | 基因技术公司 | 皮下施用的抗-il-6受体抗体 |
TWI603739B (zh) | 2010-11-11 | 2017-11-01 | 艾伯維生物技術有限責任公司 | 具有增進高濃度之抗-TNFα抗體之液體調配物 |
CN103930124B (zh) | 2011-07-01 | 2021-05-11 | 生物基因Ma公司 | 无精氨酸的tnfr:fc-融合多肽组合物及使用方法 |
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 |
TWI589299B (zh) | 2011-10-11 | 2017-07-01 | 再生元醫藥公司 | 用於治療類風濕性關節炎之組成物及其使用方法 |
SG11201401360XA (en) | 2011-10-25 | 2014-05-29 | Onclave Therapeutics Ltd | Antibody formulations and methods |
EP3431104A1 (en) * | 2012-03-26 | 2019-01-23 | Sanofi | Stable igg4 binding agent formulations |
US9592289B2 (en) | 2012-03-26 | 2017-03-14 | Sanofi | Stable IgG4 based binding agent formulations |
CN104271600B (zh) | 2012-05-14 | 2018-09-14 | 诺和诺德股份有限公司 | 稳定化的蛋白溶液 |
SG10201709555SA (en) | 2012-05-18 | 2017-12-28 | Genentech Inc | High-concentration monoclonal antibody formulations |
AR092325A1 (es) | 2012-05-31 | 2015-04-15 | Regeneron Pharma | Formulaciones estabilizadas que contienen anticuerpos anti-dll4 y kit |
CN104685359B (zh) * | 2012-07-31 | 2017-09-05 | 积水医疗株式会社 | 胶乳凝集抑制免疫测定 |
US8613919B1 (en) | 2012-08-31 | 2013-12-24 | Bayer Healthcare, Llc | High concentration antibody and protein formulations |
UA115789C2 (uk) * | 2012-09-05 | 2017-12-26 | Трейкон Фармасутікалз, Інк. | Композиція антитіла до cd105 та її застосування |
BR112015032960B1 (pt) | 2013-07-04 | 2021-01-05 | F. Hoffmann-La Roche Ag | imunoensaio suprimido por interferência para detectar anticorpos anti-fármaco em amostras de soro |
US9017678B1 (en) | 2014-07-15 | 2015-04-28 | Kymab Limited | Method of treating rheumatoid arthritis using antibody to IL6R |
EP2960252A1 (en) * | 2014-06-26 | 2015-12-30 | Institut Pasteur | Phospholipase for treatment of immunosuppression |
US9926375B2 (en) | 2014-11-12 | 2018-03-27 | Tracon Pharmaceuticals, Inc. | Anti-endoglin antibodies and uses thereof |
US10155820B2 (en) | 2014-11-12 | 2018-12-18 | Tracon Pharmaceuticals, Inc. | Anti-endoglin antibodies and uses thereof |
CN107206080B (zh) | 2015-01-28 | 2022-07-08 | 辉瑞公司 | 稳定的水性抗血管内皮细胞生长因子(vegf)抗体制剂 |
WO2016123521A2 (en) | 2015-01-30 | 2016-08-04 | Momenta Pharmaceuticals, Inc. | Fcrn antibodies and methods of use thereof |
EP3053572A1 (en) * | 2015-02-06 | 2016-08-10 | Ares Trading S.A. | Liquid pharmaceutical composition |
EP3347403B1 (en) | 2015-09-11 | 2020-03-25 | Dow Global Technologies LLC | Polyalkoxy fatty compound |
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 |
RU2019112680A (ru) | 2016-09-27 | 2020-10-29 | Фрезениус Каби Дойчланд Гмбх | Жидкая фармацевтическая композиция |
JP6884858B2 (ja) | 2016-10-21 | 2021-06-09 | アムジエン・インコーポレーテツド | 医薬製剤及びその製造方法 |
BR112019006853B1 (pt) | 2016-10-31 | 2021-08-24 | Fresenius Kabi Deutschland Gmbh | Composição farmacêutica líquida, seu método de fabricação, seu uso, kit e dispositivo de liberação de fármaco que a compreendem e método de fabricação do dito dispositivo |
US11033496B2 (en) | 2017-03-17 | 2021-06-15 | The Regents Of The University Of Michigan | Nanoparticles for delivery of chemopreventive agents |
JPWO2018179138A1 (ja) * | 2017-03-29 | 2020-02-06 | 持田製薬株式会社 | 抗体含有液体製剤 |
WO2018187074A1 (en) | 2017-04-03 | 2018-10-11 | Immunomedics, Inc. | Subcutaneous administration of antibody-drug conjugates for cancer therapy |
BR112020005335A2 (pt) * | 2017-09-19 | 2020-09-24 | Regeneron Pharmaceuticals, Inc. | métodos para reduzir a formação de partículas e composições formadas pelos mesmos |
CN107966567B (zh) * | 2017-11-21 | 2018-12-18 | 浙江夸克生物科技有限公司 | 一种触珠蛋白测定试剂盒 |
JP7420720B2 (ja) | 2017-12-13 | 2024-01-23 | モメンタ ファーマシューティカルズ インコーポレイテッド | FcRn抗体およびその使用方法 |
WO2019126133A1 (en) * | 2017-12-20 | 2019-06-27 | Alexion Pharmaceuticals, Inc. | Liquid formulations of anti-cd200 antibodies |
WO2019126536A1 (en) | 2017-12-20 | 2019-06-27 | Alexion Pharmaceuticals Inc. | Humanized anti-cd200 antibodies and uses thereof |
WO2020023310A1 (en) * | 2018-07-20 | 2020-01-30 | Williams Eva | Compositions of fcrn antibodies and methods of use thereof |
US11498969B2 (en) | 2019-01-31 | 2022-11-15 | Sanofi Biotechnology | Compositions and methods for treating juvenile idiopathic arthritis |
CR20210435A (es) | 2019-02-18 | 2021-09-20 | Lilly Co Eli | Formulación de anticuerpos terapéuticos |
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 |
JP2023517611A (ja) * | 2020-03-10 | 2023-04-26 | ティジアーナ ライフ サイエンシズ パブリック リミティド カンパニー | Il-6/il-6r抗体の組成物及びその使用方法 |
US20240025991A1 (en) | 2020-03-23 | 2024-01-25 | Genentech, Inc. | Method for treating pneumonia, including covid-19 pneumonia, with an il6 antagonist |
WO2021194861A1 (en) | 2020-03-23 | 2021-09-30 | Genentech, Inc. | Biomarkers for predicting response to il-6 antagonist in covid-19 pneumonia |
WO2021194860A1 (en) | 2020-03-23 | 2021-09-30 | Genentech, Inc. | Tocilizumab and remdesivir combination therapy for covid-19 pneumonia |
KR20220028972A (ko) * | 2020-08-31 | 2022-03-08 | (주)셀트리온 | 안정한 약제학적 제제 |
WO2022060412A1 (en) | 2020-09-17 | 2022-03-24 | Genentech, Inc. | Results of empacta: a randomized, double-blind, placebo-controlled, multicenter study to evaluate the efficacy and safety of tocilizumab in hospitalized patients with covid-19 pneumonia |
Citations (25)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0233400A2 (en) | 1985-11-25 | 1987-08-26 | Shell Oil Company | Butene-1/propylene copolymer blends |
JPH0159878B2 (ja) | 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 (en) | 1991-04-25 | 1992-11-12 | Chugai Seiyaku Kabushiki Kaisha | Reconstituted human antibody against human interleukin 6 receptor |
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 (fr) | 1994-07-13 | 1996-02-01 | Chugai Seiyaku Kabushiki Kaisha | Anticorps humain reconstitue contre l'interleukine-8 humaine |
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 |
WO1997004801A1 (en) * | 1995-07-27 | 1997-02-13 | Genentech, Inc. | Stabile isotonic lyophilized protein formulation |
WO1997045140A1 (en) * | 1996-05-24 | 1997-12-04 | Glaxo Group Limited | Concentrated antibody preparation |
WO1998014580A1 (fr) | 1996-10-04 | 1998-04-09 | Chugai Seiyaku Kabushiki Kaisha | Anticorps anti-hm1.24 humain reconstitue |
WO1998022136A2 (de) | 1996-11-19 | 1998-05-28 | Roche Diagnostics Gmbh | Stabile lyophilisierte pharmazeutische zubereitungen von mono- oder polyklonalen antikörpern |
WO1998035698A1 (fr) | 1997-02-12 | 1998-08-20 | Chugai Seiyaku Kabushiki Kaisha | Remedes contre les tumeurs lymphocitaires |
WO1998056418A1 (en) | 1997-06-13 | 1998-12-17 | Genentech, Inc. | Stabilized antibody formulation |
JPH1192399A (ja) | 1997-09-24 | 1999-04-06 | Chugai Pharmaceut Co Ltd | 骨髄腫治療剤 |
WO2000066160A1 (fr) * | 1999-04-28 | 2000-11-09 | Yamanouchi Pharmaceutical Co., Ltd. | Composition medicamenteuse parenterale a fragment d'anticorps monoclonal humanise et procede de stabilisation |
Family Cites Families (93)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4186192A (en) | 1978-12-18 | 1980-01-29 | Cutter Laboratories, Inc. | Stabilized immune serum globulin |
US4396608A (en) | 1981-08-24 | 1983-08-02 | Cutter Laboratories | Intravenously injectable immune serum globulin |
US4482483A (en) | 1983-04-06 | 1984-11-13 | Armour Pharmceutical Company | Composition of intravenous immune globulin |
JPH0825901B2 (ja) | 1984-01-05 | 1996-03-13 | 株式会社ミドリ十字 | IgG単量体 |
JPH0677019B2 (ja) | 1984-01-17 | 1994-09-28 | 株式会社ヤトロン | 酵素標識抗体の安定化法 |
JPH0825902B2 (ja) | 1985-02-21 | 1996-03-13 | 株式会社ミドリ十字 | γ−グロブリンの加熱処理方法 |
GB8607679D0 (en) | 1986-03-27 | 1986-04-30 | Winter G P | Recombinant dna product |
JPS6388197A (ja) * | 1986-09-30 | 1988-04-19 | Tosoh Corp | モノクロナル抗体の安定化方法 |
JP2547556B2 (ja) | 1987-02-06 | 1996-10-23 | 株式会社 ミドリ十字 | r−グロブリンの液状製剤 |
CA1341152C (en) | 1988-01-22 | 2000-12-12 | Tadamitsu Kishimoto | Receptor protein for human b cell stimulatory factor-2 |
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 |
US5945098A (en) | 1990-02-01 | 1999-08-31 | Baxter International Inc. | Stable intravenously-administrable immune globulin preparation |
JP3145696B2 (ja) | 1990-10-05 | 2001-03-12 | 日本ケミカルリサーチ株式会社 | 分泌型免疫グロブリンa製剤の製造法 |
US6165467A (en) | 1991-07-20 | 2000-12-26 | Yoshihide Hagiwara | Stabilized human monoclonal antibody preparation |
JP2966592B2 (ja) * | 1991-07-20 | 1999-10-25 | 萩原 義秀 | 安定化されたヒトモノクローナル抗体製剤 |
GB9122820D0 (en) | 1991-10-28 | 1991-12-11 | Wellcome Found | Stabilised antibodies |
US5777085A (en) | 1991-12-20 | 1998-07-07 | Protein Design Labs, Inc. | Humanized antibodies reactive with GPIIB/IIIA |
CH684164A5 (de) | 1992-01-10 | 1994-07-29 | Rotkreuzstiftung Zentrallab | Intravenös anwendbare Immunglobulinlösung. |
IT1254359B (it) | 1992-05-11 | 1995-09-14 | Serono Cesare Ist Ricerca | Composizioni farmaceutiche contenenti il-6 |
US5354580A (en) * | 1993-06-08 | 1994-10-11 | Cvd Incorporated | Triangular deposition chamber for a vapor deposition system |
US5888510A (en) | 1993-07-21 | 1999-03-30 | Chugai Seiyaku Kabushiki Kaisha | Chronic rheumatoid arthritis therapy containing IL-6 antagonist as effective component |
FR2708467B1 (fr) | 1993-07-30 | 1995-10-20 | Pasteur Merieux Serums Vacc | Préparations d'immunoglobulines stabilisées et procédé pour leur préparation. |
US8017121B2 (en) | 1994-06-30 | 2011-09-13 | Chugai Seiyaku Kabushika Kaisha | Chronic rheumatoid arthritis therapy containing IL-6 antagonist as effective component |
JP3630453B2 (ja) | 1994-09-30 | 2005-03-16 | 中外製薬株式会社 | 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 |
RU2147443C1 (ru) | 1994-10-07 | 2000-04-20 | Чугаи Сейяку Кабусики Кайся | Лечебные средства против хронического ревматоидного артрита, содержащие антагонист il-6 в качестве эффективного компонента |
EP0791359A4 (en) | 1994-10-21 | 2002-09-11 | Chugai Pharmaceutical Co Ltd | MEDICINE AGAINST IL-6 PRODUCTION IN DISEASES |
KR100252743B1 (ko) | 1994-12-29 | 2000-09-01 | 나가야마 오사무 | Il-6 안타고니스트를 함유하는 항종양제의 작용증강제 |
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. |
US5656730A (en) * | 1995-04-07 | 1997-08-12 | Enzon, Inc. | Stabilized monomeric protein compositions |
US6267958B1 (en) * | 1995-07-27 | 2001-07-31 | Genentech, Inc. | Protein formulation |
US6685940B2 (en) | 1995-07-27 | 2004-02-03 | Genentech, Inc. | Protein formulation |
EP0923941B1 (en) | 1996-06-27 | 2006-05-17 | Chugai Seiyaku Kabushiki Kaisha | Remedies for myeloma to be used together with nitrogen mustard antitumor agents |
US6903194B1 (en) | 1996-09-26 | 2005-06-07 | Chungai Seiyaku Kabushiki Kaisha | Antibody against human parathormone related peptides |
AT412600B (de) | 1996-10-29 | 2005-04-25 | Bernhard Dipl Ing Rzepa | Schaltungsanordnung zur hysteresebehafteten schwellwertdetektion des spitzenwertes eines periodischen eingangssignales |
TW541179B (en) | 1997-03-19 | 2003-07-11 | Green Cross Corp | Process for preparing immunoglobulin preparation |
GB9705810D0 (en) * | 1997-03-20 | 1997-05-07 | Common Services Agency | Intravenous immune globulin |
ES2312184T3 (es) | 1997-03-21 | 2009-02-16 | Chugai Seiyaku Kabushiki Kaisha | Agentes preventivos terapeuticos para el tratamiento de esclerosis multiple, que contienen anticuerpos anti-receptores de il-6 antagonistas. |
US6171586B1 (en) * | 1997-06-13 | 2001-01-09 | 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 |
US6159471A (en) * | 1997-10-23 | 2000-12-12 | Yoshitomi Pharmaceutical Industries, Ltd. | Room temperature storable immunoglobulin preparation for intravenous injection |
CN100374159C (zh) | 1998-03-17 | 2008-03-12 | 中外制药株式会社 | 一种包含il-6拮抗剂活性成分的炎性肠道疾病的预防或治疗剂 |
AU757910B2 (en) * | 1998-04-02 | 2003-03-13 | Genentech Inc. | Treatment of cardiac hypertrophy |
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 |
WO2000000219A1 (fr) | 1998-06-26 | 2000-01-06 | Chugai Seiyaku Kabushiki Kaisha | Remedes contre des crises d'hypercalcemie |
US6406909B1 (en) | 1998-07-10 | 2002-06-18 | Chugai Seiyaku Kabushiki Kaisha | Serum-free medium for culturing animal cells |
ES2276525T3 (es) | 1998-08-24 | 2007-06-16 | Chugai Seiyaku Kabushiki Kaisha | Preventivos o remedios para la pancreatitis que contienen anticuerpos anti-receptor il-6 como ingrediente activo. |
JP2003516111A (ja) | 1999-02-22 | 2003-05-13 | バリアジェニックス インコーポレーテッド | 疾病の治療法の決定において有用性を有する遺伝子配列変異 |
US20020165178A1 (en) * | 2000-06-28 | 2002-11-07 | Christian Schetter | Immunostimulatory nucleic acids for the treatment of anemia, thrombocytopenia, and neutropenia |
FR2811869B1 (fr) | 2000-07-21 | 2002-12-13 | Salomon Sa | Dispositif de serrage pour article chaussant |
JP4812228B2 (ja) | 2000-08-10 | 2011-11-09 | 中外製薬株式会社 | 抗体含有溶液の凝集物生成または白濁抑制方法 |
JP5485489B2 (ja) | 2000-08-11 | 2014-05-07 | 中外製薬株式会社 | 抗体含有安定化製剤 |
CN1259973C (zh) | 2000-10-25 | 2006-06-21 | 中外制药株式会社 | 含有il-6拮抗剂作为有效成分的牛皮癣的预防或治疗剂 |
AU2000279625A1 (en) | 2000-10-27 | 2002-05-15 | Chugai Seiyaku Kabushiki Kaisha | Blood mmp-3 level-lowering agent containing il-6 antgonist as the active ingredient |
US7332289B2 (en) | 2001-03-09 | 2008-02-19 | Chugai Seiyaku Kabushiki Kaisha | Method of purifying protein |
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 |
EP3192528A1 (en) | 2002-02-14 | 2017-07-19 | Chugai Seiyaku Kabushiki Kaisha | Formulation of anti-il6r antibody-containing solutions comprising a sugar as a stabilizer |
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 |
AU2003265361A1 (en) * | 2002-08-28 | 2004-03-19 | Pharmacia Corporation | Stable ph optimized formulation of a modified antibody |
AU2003262087B2 (en) | 2002-09-11 | 2010-11-11 | Chugai Seiyaku Kabushiki Kaisha | Protein purification method |
CN100340294C (zh) | 2003-02-24 | 2007-10-03 | 中外制药株式会社 | 含有白介素6拮抗剂的脊髓损伤治疗剂 |
GB2401040A (en) | 2003-04-28 | 2004-11-03 | Chugai Pharmaceutical Co Ltd | Method for treating interleukin-6 related diseases |
NZ546557A (en) | 2003-10-17 | 2010-01-29 | Chugai Pharmaceutical Co Ltd | Therapeutic agent for mesothelioma comprising interleukin-6 |
US8617550B2 (en) | 2003-12-19 | 2013-12-31 | Chugai Seiyaku Kabushiki Kaisha | Treatment of vasculitis with IL-6 antagonist |
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 |
KR20130101161A (ko) | 2005-01-05 | 2013-09-12 | 추가이 세이야쿠 가부시키가이샤 | 세포의 배양 방법 및 그 이용 |
AU2006259536A1 (en) * | 2005-06-15 | 2006-12-28 | Schering Corporation | Anti-IGF1R antibody formulations |
WO2007043641A1 (ja) | 2005-10-14 | 2007-04-19 | Fukuoka University | 膵島移植における移植膵島障害抑制剤 |
BRPI0617664B8 (pt) | 2005-10-21 | 2021-05-25 | Chugai Pharmaceutical Co Ltd | uso de um anticorpo que reconhece a il-6 para a produção de uma composição farmacêutica para tratar o enfarte do miocárdio ou suprimir a remodelagem ventricular esquerda depois do enfarte do miocárdio |
AR057582A1 (es) | 2005-11-15 | 2007-12-05 | Nat Hospital Organization | Agentes para suprimir la induccion de linfocitos t citotoxicos |
AR057941A1 (es) | 2005-11-25 | 2007-12-26 | Univ Keio | Agentes terapeuticos para el cancer de prostata |
US9084777B2 (en) | 2005-12-28 | 2015-07-21 | Chugai Seiyaku Kabushiki Kaisha | Stabilized antibody-containing formulations |
EP3135298B1 (en) | 2006-01-27 | 2018-06-06 | Keio University | Therapeutic agents for diseases involving choroidal neovascularization |
CN101495146B (zh) | 2006-04-07 | 2012-10-17 | 国立大学法人大阪大学 | 肌肉再生促进剂 |
WO2008016134A1 (fr) | 2006-08-04 | 2008-02-07 | Norihiro Nishimoto | PROCÉDÉ POUR PRÉDIRE LE PRONOSTIC DES PATIENTS ATTEINTS DE POLYARTHRITE rhumatoïde |
TW200831528A (en) | 2006-11-30 | 2008-08-01 | Astrazeneca Ab | Compounds |
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 |
TWI438208B (zh) | 2007-01-23 | 2014-05-21 | Chugai Pharmaceutical Co Ltd | 抑制慢性排斥反應之藥劑 |
JP5424330B2 (ja) | 2007-07-26 | 2014-02-26 | 国立大学法人大阪大学 | インターロイキン6受容体阻害剤を有効成分とする眼炎症疾患治療剤 |
CL2008002885A1 (es) | 2007-09-26 | 2010-07-02 | Chugai Pharmaceutical Co Ltd | Anticuerpo anti-receptor de interleucina-6 (il-6); y composicion farmaceutica que lo comprende |
KR101601986B1 (ko) | 2007-10-02 | 2016-03-17 | 추가이 세이야쿠 가부시키가이샤 | 인터류킨 6 수용체 저해제를 유효 성분으로 하는 이식편대숙주병 치료제 |
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 |
US8227195B2 (en) | 2007-12-15 | 2012-07-24 | Hoffman-La Roche Inc. | Distinguishing assay |
PE20091174A1 (es) | 2007-12-27 | 2009-08-03 | Chugai Pharmaceutical Co Ltd | Formulacion liquida con contenido de alta concentracion de anticuerpo |
KR101665729B1 (ko) | 2008-06-05 | 2016-10-12 | 국립연구개발법인 고쿠리츠간켄큐센터 | 신경침윤 억제제 |
MY161541A (en) | 2009-07-31 | 2017-04-28 | Shin Maeda | Cancer metastasis inhibitor |
DK2493922T3 (en) | 2009-10-26 | 2017-04-24 | Hoffmann La Roche | Process for preparing a glycosylated immunoglobulin |
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 |
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 |
DK2578231T3 (da) | 2010-05-28 | 2022-12-12 | Chugai Pharmaceutical Co Ltd | Antitumor-t-celle-reaktionsforstærker |
EP2576824A2 (en) | 2010-06-07 | 2013-04-10 | Roche Diagnostics GmbH | Gene expression markers for predicting response to interleukin-6 receptor-inhibiting monoclonal antibody drug treatment |
CN103476793A (zh) | 2010-11-08 | 2013-12-25 | 基因技术公司 | 皮下施用的抗-il-6受体抗体 |
-
2003
- 2003-02-14 EP EP17155264.9A patent/EP3192528A1/en not_active Withdrawn
- 2003-02-14 SI SI200331916T patent/SI1475101T1/sl unknown
- 2003-02-14 MX MXPA04007924A patent/MXPA04007924A/es active IP Right Grant
- 2003-02-14 JP JP2003567439A patent/JP4364645B2/ja not_active Expired - Lifetime
- 2003-02-14 EP EP03705166A patent/EP1475101B1/en not_active Expired - Lifetime
- 2003-02-14 KR KR1020107005331A patent/KR101080021B1/ko active Protection Beyond IP Right Term
- 2003-02-14 JP JP2003567440A patent/JP3792698B2/ja not_active Expired - Lifetime
- 2003-02-14 CA CA2474943A patent/CA2474943C/en not_active Expired - Lifetime
- 2003-02-14 EP EP19157205.6A patent/EP3578168A1/en active Pending
- 2003-02-14 US US10/504,025 patent/US20050118163A1/en not_active Abandoned
- 2003-02-14 ES ES03705166T patent/ES2353496T3/es not_active Expired - Lifetime
- 2003-02-14 AT AT03705166T patent/ATE485835T1/de active
- 2003-02-14 NZ NZ534542A patent/NZ534542A/en not_active IP Right Cessation
- 2003-02-14 BR BRPI0307702A patent/BRPI0307702B8/pt not_active IP Right Cessation
- 2003-02-14 CN CNA2007101051496A patent/CN101066450A/zh active Pending
- 2003-02-14 WO PCT/JP2003/001563 patent/WO2003068260A1/ja active Application Filing
- 2003-02-14 AU AU2003211991A patent/AU2003211991B2/en not_active Expired
- 2003-02-14 EP EP20030705165 patent/EP1475100B1/en not_active Expired - Lifetime
- 2003-02-14 RU RU2004127446/15A patent/RU2335299C2/ru active Protection Beyond IP Right Term
- 2003-02-14 KR KR10-2004-7012494A patent/KR20040085185A/ko not_active Application Discontinuation
- 2003-02-14 CN CNA038050528A patent/CN1638798A/zh active Pending
- 2003-02-14 PT PT03705166T patent/PT1475101E/pt unknown
- 2003-02-14 KR KR1020117017489A patent/KR20110091822A/ko not_active Application Discontinuation
- 2003-02-14 PL PL372097A patent/PL213311B1/pl unknown
- 2003-02-14 EP EP10010404.1A patent/EP2311489A3/en not_active Ceased
- 2003-02-14 DE DE60334678T patent/DE60334678D1/de not_active Expired - Lifetime
- 2003-02-14 CN CN200910253760.2A patent/CN101721362B/zh not_active Expired - Lifetime
- 2003-02-14 US US10/503,720 patent/US8840884B2/en not_active Expired - Lifetime
- 2003-02-14 ES ES03705165.3T patent/ES2536709T3/es not_active Expired - Lifetime
- 2003-02-14 AU AU2003211990A patent/AU2003211990A1/en not_active Abandoned
- 2003-02-14 WO PCT/JP2003/001562 patent/WO2003068259A1/ja active Application Filing
- 2003-02-14 DK DK03705166.1T patent/DK1475101T3/da active
-
2004
- 2004-04-14 JP JP2004119277A patent/JP4601989B2/ja not_active Expired - Lifetime
- 2004-08-04 HR HR20040710 patent/HRP20040710B1/xx not_active IP Right Cessation
- 2004-08-04 IL IL163354A patent/IL163354A/en active IP Right Grant
- 2004-08-04 ZA ZA200406230A patent/ZA200406230B/en unknown
- 2004-08-12 NO NO20043353A patent/NO333553B1/no not_active IP Right Cessation
- 2004-09-10 CO CO04090189A patent/CO5611163A2/es not_active Application Discontinuation
-
2008
- 2008-08-01 US US12/184,551 patent/US8921527B2/en active Active
- 2008-11-11 AU AU2008243208A patent/AU2008243208B2/en not_active Expired
-
2009
- 2009-01-07 US US12/349,986 patent/US9051384B2/en not_active Expired - Lifetime
-
2010
- 2010-05-17 JP JP2010113308A patent/JP5280401B2/ja not_active Expired - Lifetime
-
2011
- 2011-01-04 CY CY20111100012T patent/CY1111073T1/el unknown
- 2011-03-22 CY CY2011003C patent/CY2011003I2/el unknown
Patent Citations (30)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH0159878B2 (ja) | 1982-05-21 | 1989-12-20 | Yunibaashitei Obu Karifuorunia | |
EP0233400A2 (en) | 1985-11-25 | 1987-08-26 | Shell Oil Company | Butene-1/propylene copolymer blends |
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 |
EP0628639A1 (en) * | 1991-04-25 | 1994-12-14 | Chugai Seiyaku Kabushiki Kaisha | Reconstituted human antibody against human interleukin 6 receptor |
WO1992019759A1 (en) | 1991-04-25 | 1992-11-12 | Chugai Seiyaku Kabushiki Kaisha | Reconstituted human antibody against human interleukin 6 receptor |
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 (fr) | 1994-07-13 | 1996-02-01 | Chugai Seiyaku Kabushiki Kaisha | Anticorps humain reconstitue contre l'interleukine-8 humaine |
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 |
WO1997004801A1 (en) * | 1995-07-27 | 1997-02-13 | Genentech, Inc. | Stabile isotonic lyophilized protein formulation |
WO1997045140A1 (en) * | 1996-05-24 | 1997-12-04 | Glaxo Group Limited | Concentrated antibody preparation |
US6252055B1 (en) | 1996-05-24 | 2001-06-26 | Glaxo Wellcome Inc. | Concentrated antibody preparation |
EP0960936A1 (en) * | 1996-10-04 | 1999-12-01 | Chugai Seiyaku Kabushiki Kaisha | Reconstituted human anti-hm1.24 antibody |
WO1998014580A1 (fr) | 1996-10-04 | 1998-04-09 | Chugai Seiyaku Kabushiki Kaisha | Anticorps anti-hm1.24 humain reconstitue |
WO1998022136A2 (de) | 1996-11-19 | 1998-05-28 | Roche Diagnostics Gmbh | Stabile lyophilisierte pharmazeutische zubereitungen von mono- oder polyklonalen antikörpern |
JP2001503781A (ja) | 1996-11-19 | 2001-03-21 | ロシュ ダイアグノスティクス ゲゼルシャフト ミット ベシュレンクテル ハフツング | モノクローナル抗体又はポリクローナル抗体の安定な凍結乾燥された医薬製剤 |
WO1998035698A1 (fr) | 1997-02-12 | 1998-08-20 | Chugai Seiyaku Kabushiki Kaisha | Remedes contre les tumeurs lymphocitaires |
WO1998056418A1 (en) | 1997-06-13 | 1998-12-17 | Genentech, Inc. | Stabilized antibody formulation |
JPH1192399A (ja) | 1997-09-24 | 1999-04-06 | Chugai Pharmaceut Co Ltd | 骨髄腫治療剤 |
WO2000066160A1 (fr) * | 1999-04-28 | 2000-11-09 | Yamanouchi Pharmaceutical Co., Ltd. | Composition medicamenteuse parenterale a fragment d'anticorps monoclonal humanise et procede de stabilisation |
EP1174148A1 (en) | 1999-04-28 | 2002-01-23 | Yamanouchi Pharmaceutical Co. Ltd. | Parenteral medicinal composition containing humanized monoclonal antibody fragment and method for stabilizing the same |
Non-Patent Citations (3)
Title |
---|
CARL, A. K. BORREBAECK; JAMES, W. LARRICK: "THERAPEUTIC MONOCLONAL ANTIBODIES", 1990, YACMILLAN PUBLISHERS LTD |
KOHLER, G.; MILSTEIN, C., METHODS ENZYMOL., vol. 73, 1981, pages 3 - 46 |
SATO, K. ET AL., CANCER RES., vol. 53, 1993, pages 851 - 856 |
Cited By (40)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US8840884B2 (en) | 2002-02-14 | 2014-09-23 | Chugai Seiyaku Kabushiki Kaisha | Antibody-containing solution pharmaceuticals |
US9051384B2 (en) | 2002-02-14 | 2015-06-09 | Chugai Seiyaku Kabushiki Kaisha | Antibody-containing solution formulations |
US8349321B2 (en) | 2003-02-10 | 2013-01-08 | Elan Pharmaceuticals, Inc. | Immunoglobulin formulation and method of preparation thereof |
EP1592440A4 (en) * | 2003-02-10 | 2007-07-11 | Elan Pharm Inc | IMMUNOGLOBULIN PREPARATION AND METHOD OF PRODUCING THE SAME |
US8815236B2 (en) | 2003-02-10 | 2014-08-26 | Biogen Idec Ma Inc. | Method for treating multiple sclerosis and crohn's disease |
US8900577B2 (en) | 2003-02-10 | 2014-12-02 | Biogen Idec Ma Inc. | Immunoglobulin formulation and method of preparation thereof |
US10744201B2 (en) | 2003-04-28 | 2020-08-18 | Chugai Seiyaku Kabushiki Kaisha | Method for treating rheumatoid arthritis with a human IL-6 receptor antibody and methotrexate |
EP1698640B1 (en) | 2003-10-01 | 2015-12-30 | Kyowa Hakko Kirin Co., Ltd. | Method of stabilizing antibody and stabilized solution-type antibody preparation |
US10172790B2 (en) | 2003-10-01 | 2019-01-08 | Kyowa Hakko Kirin Co., Ltd | Method of stabilizing antibody and stabilized solution-type antibody preparation |
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 |
JP2008540684A (ja) * | 2005-05-19 | 2008-11-20 | アムジェン インコーポレイテッド | 抗体の安定性を増加させるための組成物および方法 |
JP5231810B2 (ja) * | 2005-12-28 | 2013-07-10 | 中外製薬株式会社 | 抗体含有安定化製剤 |
WO2007074880A1 (ja) * | 2005-12-28 | 2007-07-05 | Chugai Seiyaku Kabushiki Kaisha | 抗体含有安定化製剤 |
US11008394B2 (en) | 2007-12-27 | 2021-05-18 | Chugai Seiyaku Kabushiki Kaisha | High concentration antibody-containing liquid formulation |
US11767363B2 (en) | 2007-12-27 | 2023-09-26 | 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 |
US8568720B2 (en) | 2007-12-27 | 2013-10-29 | Chugai Seiyaku Kabushiki Kaisha | High concentration antibody-containing liquid formulation |
US11359026B2 (en) | 2007-12-27 | 2022-06-14 | Chugai Seiyaku Kabushiki Kaisha | High concentration antibody-containing liquid formulation |
US8562991B2 (en) | 2008-09-26 | 2013-10-22 | Chugai Seiyaku Kabushiki Kaisha | Antibody molecules that bind to IL-6 receptor |
US10662245B2 (en) | 2008-09-26 | 2020-05-26 | Chugai Seiyaku Kabushiki Kaisha | Methods of reducing IL-6 activity for disease treatment |
WO2010106812A1 (en) * | 2009-03-19 | 2010-09-23 | Chugai Seiyaku Kabushiki Kaisha | Pharmaceutical formulation containing improved antibody molecules |
JP2011173918A (ja) * | 2009-03-19 | 2011-09-08 | Chugai Pharmaceut Co Ltd | 改良された抗体分子を含有する製剤 |
JP2012504106A (ja) * | 2009-03-19 | 2012-02-16 | 中外製薬株式会社 | 改良された抗体分子を含有する製剤 |
US11021728B2 (en) | 2009-10-26 | 2021-06-01 | Hoffmann-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 |
US11377678B2 (en) | 2009-10-26 | 2022-07-05 | Hoffman-La Roche Inc. | Method for the production of a glycosylated immunoglobulin |
US10022319B2 (en) | 2010-01-20 | 2018-07-17 | Chugai Seiyaku Kabushiki Kaisha | Stabilized antibody-containing liquid formulations |
US11612562B2 (en) | 2010-01-20 | 2023-03-28 | Chugai Seiyaku Kabushiki Kaisha | Solution preparation containing stabilized antibody |
US10709782B2 (en) | 2010-02-26 | 2020-07-14 | Novo Nordisk A/S | Stable antibody containing compositions |
US9795674B2 (en) | 2010-02-26 | 2017-10-24 | Novo Nordisk A/S | Stable antibody containing compositions |
USRE47150E1 (en) | 2010-03-01 | 2018-12-04 | Bayer Healthcare Llc | Optimized monoclonal antibodies against tissue factor pathway inhibitor (TFPI) |
US10835602B2 (en) | 2010-05-28 | 2020-11-17 | Novo Nordisk A/S | Stable multi-dose compositions comprising an antibody and a preservative |
US9855331B2 (en) | 2010-09-17 | 2018-01-02 | Baxalta Incorporated | Stabilization of immunoglobulins through aqueous formulation with histidine at weak acidic to neutral pH |
JP2017071631A (ja) * | 2010-09-17 | 2017-04-13 | バクスアルタ ゲーエムベーハー | 弱酸性〜中性のpHにおける、ヒスチジンを有する水性製剤を介した免疫グロブリンの安定化 |
US9849181B2 (en) | 2012-08-31 | 2017-12-26 | Bayer Healthcare Llc | High concentration antibody and protein formulations |
US9592297B2 (en) | 2012-08-31 | 2017-03-14 | Bayer Healthcare Llc | Antibody and protein formulations |
US10774148B2 (en) | 2015-02-27 | 2020-09-15 | Chugai Seiyaku Kabushiki Kaisha | Composition for treating IL-6-related diseases |
CN108025033A (zh) * | 2015-09-11 | 2018-05-11 | 陶氏环球技术有限责任公司 | 包含蛋白质和聚烷氧基脂肪族化合物的组合物 |
CN108025033B (zh) * | 2015-09-11 | 2022-02-22 | 陶氏环球技术有限责任公司 | 包含蛋白质和聚烷氧基脂肪族化合物的组合物 |
US11851486B2 (en) | 2017-05-02 | 2023-12-26 | National Center Of Neurology And Psychiatry | Method for predicting and evaluating therapeutic effect in diseases related to IL-6 and neutrophils |
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
WO2003068259A1 (en) | Antibody-containing solution pharmaceuticals | |
JP6567024B2 (ja) | 高濃度抗体含有溶液製剤 | |
JP5231810B2 (ja) | 抗体含有安定化製剤 | |
JP4607010B2 (ja) | タンパク質含有安定化製剤 | |
WO2019225568A1 (ja) | ガラス容器に封入された凍結乾燥製剤 | |
WO2003018056A1 (fr) | Preparations stabilisees contenant un anticorps | |
JP2010241718A (ja) | 安定な抗体の水溶液製剤 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
AK | Designated states |
Kind code of ref document: A1 Designated state(s): AE AG AL AM AT AU AZ BA BB BG BR BY BZ CA CH CN CO CR CU CZ DE DK DM DZ EC EE ES FI GB GD GE GH GM HR HU ID IL IN IS JP KE KG KP KR KZ LC LK LR LS LT LU LV MA MD MG MK MN MW MX MZ NO NZ OM PH PL PT RO RU SC SD SE SG SK SL TJ TM TN TR TT TZ UA UG US UZ VC VN YU ZA ZM ZW |
|
AL | Designated countries for regional patents |
Kind code of ref document: A1 Designated state(s): GH GM KE LS MW MZ SD SL SZ TZ UG ZM ZW AM AZ BY KG KZ MD RU TJ TM AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HU IE IT LU MC NL PT SE SI SK TR BF BJ CF CG CI CM GA GN GQ GW ML MR NE SN TD TG |
|
DFPE | Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101) | ||
121 | Ep: the epo has been informed by wipo that ep was designated in this application | ||
WWE | Wipo information: entry into national phase |
Ref document number: 2003567439 Country of ref document: JP |
|
WWE | Wipo information: entry into national phase |
Ref document number: 10504025 Country of ref document: US |
|
WWE | Wipo information: entry into national phase |
Ref document number: 2003705165 Country of ref document: EP |
|
WWP | Wipo information: published in national office |
Ref document number: 2003705165 Country of ref document: EP |