WO2015190378A1 - 安定なアダリムマブ水性製剤 - Google Patents
安定なアダリムマブ水性製剤 Download PDFInfo
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- WO2015190378A1 WO2015190378A1 PCT/JP2015/066136 JP2015066136W WO2015190378A1 WO 2015190378 A1 WO2015190378 A1 WO 2015190378A1 JP 2015066136 W JP2015066136 W JP 2015066136W WO 2015190378 A1 WO2015190378 A1 WO 2015190378A1
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- pharmaceutical composition
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- adalimumab
- buffer
- histidine
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- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
- A61K39/39591—Stabilisation, fragmentation
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- A—HUMAN NECESSITIES
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- 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
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- 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
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- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/22—Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones
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- A61K9/00—Medicinal preparations characterised by special physical form
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/19—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles lyophilised, i.e. freeze-dried, solutions or dispersions
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
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- A61P17/00—Drugs for dermatological disorders
- A61P17/06—Antipsoriatics
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
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- 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
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
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- A—HUMAN NECESSITIES
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- 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
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- 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
- C07K16/24—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against cytokines, lymphokines or interferons
- C07K16/241—Tumor Necrosis Factors
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- A—HUMAN NECESSITIES
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- 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
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
- C07K2317/21—Immunoglobulins specific features characterized by taxonomic origin from primates, e.g. man
Definitions
- the present invention relates to a pharmaceutical composition containing adalimumab and a method for producing the pharmaceutical composition.
- polypeptide pharmaceuticals are prone to physical changes such as various chemical changes and aggregation during the manufacturing process and storage due to the complex structure of the polypeptide. It is generally known that these changes not only reduce the pharmacological action but also have a great influence on safety such as immunogenicity.
- Non-Patent Document 1 In the preparation of polypeptide pharmaceuticals, a pharmaceutical formulation capable of stably storing a polypeptide used as an active ingredient is required (Nat. Rev. Drug. Discov., 2005, 4 (4), 298- 306 (Non-Patent Document 1)).
- degradation of a polypeptide includes degradation accompanied by chemical modification such as hydrolysis, deamidation, and methionine oxidation (Int. J. Pharm., 1999, 185, 129-188 (Non-patent Document 2)) and aggregation. , Degradation associated with physical association such as cleavage and denaturation (Int. J. Pharm., 2005, 289, 1-30 (non-patent document 3)).
- the method includes selection of dosage form; optimization of solution pH; optimization of the type and concentration of buffers, salts, and stabilizers.
- Adalimumab a polypeptide (antibody) used in the treatment of collagen diseases and autoimmune diseases such as rheumatoid arthritis, as well as many other polypeptides, is physically caused by temperature, humidity, light, etc. It is assumed that the activity and chemical changes occur, resulting in decreased activity.
- aqueous preparations that can be used as liquid preparations are excellent in convenience.
- additives such as stabilizers.
- saccharides, amino acids, water-soluble polymers, nonionic surfactants, buffers and the like are used as the additive.
- WO2013 / 186230 (patented)
- succinate buffer pH 6.25, histidine buffer pH 6.25, and acetic acid and arginine buffer pH 6.5 are used.
- a succinic acid buffer solution, a histidine buffer solution, and a tartrate buffer solution (all are pH 5.2) are used.
- Adalimumab is an active ingredient of a pharmaceutical composition marketed as “Humira (registered trademark)” by Abbott, and is used as a human anti-human TNF ⁇ monoclonal for the treatment of autoimmune diseases such as rheumatoid arthritis, psoriasis, and Crohn's disease. It is an antibody.
- “Humila®” contains about 50 mg / mL of adalimumab, 6.17 mg / mL of NaCl, 12 mg / mL of mannitol and 1 mg / mL of polysorbate 80 in a 14.1 mM phosphate-4.2 mM citrate buffer. An aqueous liquid formulation having a pH of about 5.2. For this reason, adalimumab is generally considered stable at pH 5.2.
- Citric acid blended in injections is known to cause pain (Am J Kidney y Dis., 1993, Oct 22 (4), 553-556 (Non-patent Document 4), Clin Nephrol, 1998, Jan 49 (1), 41-44 (non-patent document 5)).
- “Humila (registered trademark)” is formulated with citric acid and has a relatively low pH of about 5.2, which is considered to cause pain during administration.
- An object of the present invention is to provide a stable and convenient adalimumab aqueous preparation.
- the inventors of the present invention have arrived at the present invention as a result of intensive studies to achieve the above object. That is, the present inventors use an aqueous adalimumab formulation that is superior in stability compared to conventional ones by using a combination of specific buffers among various buffers and making the pH within a specific range. I found out that
- the present invention provides: (1) A pharmaceutical composition which is an aqueous liquid preparation containing adalimumab, a histidine buffer and a phosphate buffer as buffers, and having a pH of 5.5 to 6.1. (2) The pharmaceutical composition according to (1), further comprising at least one additive selected from a buffer, an excipient, and an isotonic agent. (3) The pharmaceutical composition according to (1) or (2), wherein the concentration of histidine is 5 mM to 50 mM. (4) The pharmaceutical composition according to any one of (1) to (3), wherein the concentration of phosphoric acid is 1 mM to 20 mM. (5) A pharmaceutical composition which is a frozen preparation obtained by freezing the pharmaceutical composition according to any one of (1) to (4).
- a pharmaceutical preparation wherein the pharmaceutical composition according to any one of (1) to (4) is stored in a prefilled sterile syringe.
- (7) including at least one of the pharmaceutical composition according to any one of (1) to (5) and the pharmaceutical preparation according to (6), and a specification of the pharmaceutical composition Kit preparation.
- the stability of adalimumab in an aqueous preparation can be improved by taking the constitution of the present invention. This is expected to improve the stability of the pharmaceutical composition containing adalimumab and prevent the decrease of the pharmacological action, and to improve the safety such as the reduction of immunogenicity. In addition, it is expected that pain at the time of injection can be reduced and the burden on the patient can be reduced.
- the present invention aims to stabilize an aqueous preparation containing a polypeptide adalimumab (hereinafter sometimes referred to as “adalimumab aqueous preparation”) by blending a histidine buffer and a phosphate buffer as a buffer. is there.
- the term “pharmaceutical composition” is understood to refer to a preparation (pharmaceutical preparation) containing a peptide prepared so as to be suitable for injection and / or administration to a patient in need of treatment.
- the pharmaceutical composition may contain a buffer, an isotonic agent, an excipient and the like in addition to the buffer solution.
- aqueous preparation is understood to refer to a preparation using water as a solvent
- adalimumab aqueous preparation is understood to refer to a preparation containing at least water and adalimumab.
- additives such as a buffering agent, an isotonic agent, and an excipient may be contained.
- the “aqueous liquid preparation” is understood to refer to a liquid preparation using water as a solvent among the forms of the aqueous preparation, and the “frozen preparation” is formed by freezing the aqueous liquid preparation. It is understood to refer to a formulation.
- the “aqueous liquid preparation” is preferably used as an injection or an infusion, and is preferably stored in a syringe such as a pre-filled sterilized syringe or in an infusion pack.
- the “frozen preparation” is preferably used as an injection or an infusion after thawing.
- the “kit formulation” is understood to refer to a formulation comprising the pharmaceutical composition and specifications of the pharmaceutical composition, and the pharmaceutical composition includes the aqueous liquid formulation and the frozen formulation. Good.
- the pH of the pharmaceutical composition of the present invention is 5.5 to 6.1.
- “Humila (registered trademark)” is a conventional aqueous formulation of adalimumab.
- the “buffer solution” is a solution that maintains the pH of the solution within an allowable range by the action of the acid-base conjugate component.
- the buffer solution include histidine buffer solution, phosphate buffer solution, and acetate buffer. Liquid, succinate buffer, citrate buffer, and organic acid buffer. In the present invention, not only a histidine buffer and a phosphate buffer are used in combination as the buffer, but also other buffers such as an acetate buffer may be used in combination.
- “histidine buffer” means at least two kinds selected from the group consisting of histidine, histidine salts and hydrates of the histidine salts (two histidine salts or two histidine salt hydrates).
- the histidine salt includes histidine hydrochloride and the like.
- the “phosphate buffer solution” means at least two types selected from the group consisting of phosphoric acid, a phosphate, and a hydrate of the phosphate (two types of phosphate or phosphorus A buffer solution prepared from an acid salt hydrate), and examples of the phosphate include sodium phosphate and potassium phosphate.
- the “buffering agent” is a compound having a buffering action for maintaining the pH within an allowable range
- preferable buffering agents include histidine and histidine hydrochloride that can be contained in the histidine buffer and phosphate buffer.
- a histidine, histidine hydrochloride and sodium phosphate Preferably a histidine, histidine hydrochloride and sodium phosphate.
- a preferable isotonic agent in the present invention is at least one isotonic agent selected from the group consisting of sodium chloride, potassium chloride, sodium citrate, sucrose, glucose, mannitol, sorbitol, xylitol, arginine, cysteine, and histidine. Yes, more preferably sodium chloride.
- Preferred excipients in the present invention are sorbitol, mannitol, sucrose, xylitol, trehalose, glucose, lactose, glycerol, maltose, inositol, bovine serum albumin (BSA), dextran, PVA, hydroxypropyl methylcellulose (HPMC), Polyethyleneimine, gelatin, polyvinylpyrrolidone (PVP), hydroxyethyl cellulose (HEC), polyethylene glycol, ethylene glycol, dimethyl sulfoxide (DMSO), dimethylformamide (DMF), proline, sodium L-serine glutamate, potassium glutamate, alanine, lysine hydrochloride Salt, sarcosine, ⁇ -aminobutyric acid, polysorbate 20, polysorbate 80, SDS, poly Xylethylene copolymer, sodium acetate, ammonium sulfate, magnesium sulfate, sodium sulfate
- adalimumab means a protein that is a human anti-human TNF ⁇ monoclonal antibody as an active ingredient of a pharmaceutical composition marketed as “Humila (registered trademark)”, and a protein that is pharmaceutically equivalent thereto.
- “monomer” and “monomer” of adalimumab refer to an active protein of about 148 kDa.
- the “active body” in the present invention refers to a monomer of adalimumab and is understood to refer to a monomer that can be confirmed by size exclusion chromatography (SEC).
- the pharmaceutical composition of the present invention contains adalimumab, water, and histidine and phosphoric acid blended as the buffer solution (and as the buffer agent if necessary).
- the concentration of histidine in the pharmaceutical composition of the present invention is not particularly limited, but the lower limit is preferably 5 mM, more preferably 10 mM, still more preferably 15 mM, particularly preferably 20 mM, and the upper limit is preferably 50 mM. Preferably it is 30 mM, More preferably, it is 25 mM, Most preferably, it is 20 mM.
- the concentration of histidine in the pharmaceutical composition of the present invention is preferably 5 mM to 50 mM, more preferably 10 mM to 30 mM, and even more preferably 15 mM to 25 mM.
- the concentration of phosphoric acid is not particularly limited, but the lower limit is preferably 1 mM, more preferably 3 mM, and even more preferably 5 mM, and the upper limit is preferably 20 mM, more preferably 10 mM, and even more preferably 5 mM. It is.
- the concentration of phosphoric acid in the pharmaceutical composition of the present invention is preferably 1 mM to 20 mM, more preferably 3 mM to 10 mM.
- the pharmaceutical composition of the present invention does not substantially contain glycine.
- “substantially free of glycine” means that the content of glycine in the pharmaceutical composition is 6 mM or less. In the present invention, even if glycine is not contained, the stability of adalimumab in an aqueous preparation is excellent.
- adalimumab aqueous preparation (Preparation of adalimumab aqueous preparation 1) Samples (adalimumab aqueous preparation) containing various buffer solutions were prepared (Table 1). These samples contain adalimumab 50 mg / mL, NaCl 6.16 mg / mL, mannitol 12 mg / mL, polysorbate 80 1 mg / mL, and the buffer shown in Table 1 as an aqueous solution having a pH of 5.2 to 6.0. Prepared. The phosphate buffer solution is prepared from sodium dihydrogen phosphate dihydrate and disodium hydrogen phosphate dodecahydrate, and the histidine buffer solution is prepared from histidine and histidine hydrochloride monohydrate.
- the citrate buffer solution is prepared from citric acid monohydrate and trisodium citrate dihydrate, and the acid components derived from each buffer solution (phosphate, citric acid, histidine) in the combinations shown in Table 1
- the concentration (final concentration) in the aqueous adalimumab formulation was such that the concentration shown in Table 1 was obtained.
- SEC size exclusion chromatography
- IEC ion exchange chromatography
- IEC is a technique for separating biomolecules according to the characteristics of the charge exposed on the protein surface.
- cation exchange chromatography is used in the present invention to deacidify the adalimumab active body (deamidated form). The content (% acidified product (% Acidic)) in each sample was measured and evaluated.
- Formulations F4 to F6 were confirmed to have less acidified amount than Formulations F1 to F3 and to suppress the formation of deamidated products.
- Formulation F1, Formulation F2 and Formulation F3 have 33.5, 34.4 and 32.6 percent acidified form, whereas Formulation F4, Formulation F5 and Formulation F6 have 3% acidified form.
- Formulations F4 to F6 were preparations having excellent stability, as low as 31.1 and 31.0 (FIG. 2).
- adalimumab aqueous preparation 2 (Preparation of adalimumab aqueous preparation 2) Samples (adalimumab aqueous preparation) containing various buffer solutions were prepared (Table 2). These samples contained adalimumab 50 mg / mL, NaCl 6.16 mg / mL, mannitol 12 mg / mL, polysorbate 80 1 mg / mL, and the buffer shown in Table 2 as an aqueous solution having a pH of 5.2 to 5.5. Prepared.
- phosphate buffer and histidine buffer were prepared in the same manner as Preparation 1 of the above-mentioned adalimumab aqueous preparation, and acetate buffer was prepared from acetic acid and sodium acetate trihydrate.
- concentration (final concentration) of the buffer-derived acid components (phosphate, histidine, and acetic acid) in the aqueous adalimumab preparation was adjusted to the concentration shown in Table 2.
- the present invention shows that the stability of adalimumab is improved by using a combination of histidine buffer and phosphate buffer. Furthermore, it is considered that pain can be reduced and the burden on the patient can be reduced by not adding citric acid as an additive and adjusting the pH of the preparation to 5.5 to 6.1. This result makes it possible to provide a stable and convenient adalimumab aqueous preparation.
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Abstract
Description
(1)アダリムマブと、緩衝液としてヒスチジン緩衝液及びリン酸緩衝液とを含み、かつ、pHが5.5~6.1の水性液体製剤である医薬組成物。
(2)更に緩衝剤、賦形剤及び等張化剤のうちから選択される少なくとも一つの添加剤を含んでなる(1)に記載の医薬組成物。
(3)ヒスチジンの濃度が5mM~50mMである(1)又は(2)に記載の医薬組成物。
(4)リン酸の濃度が1mM~20mMである(1)~(3)のうちのいずれか一項に記載の医薬組成物。
(5)(1)~(4)のうちのいずれか一項に記載の医薬組成物が凍結されてなる凍結製剤である医薬組成物。
(6)(1)~(4)のうちのいずれか一項に記載の医薬組成物が予備充填滅菌注射器中に保存されている医薬製剤。
(7)(1)~(5)のうちのいずれか一項に記載の医薬組成物及び(6)に記載の医薬製剤のうちの少なくとも1つと、前記医薬組成物の仕様説明書とを含むキット製剤である。
種々の緩衝液を配合した試料(アダリムマブ水性製剤)をそれぞれ調製した(表1)。これらの試料はアダリムマブ50mg/mL、NaCl 6.16mg/mL、マンニトール12mg/mL、ポリソルベート80 1mg/mL、及び表1に示す緩衝液を含有し、pHが5.2~6.0の水溶液として調製した。また、リン酸緩衝液はリン酸二水素ナトリウム・2水和物及びリン酸水素二ナトリウム・12水和物から調製し、ヒスチジン緩衝液はヒスチジン及びヒスチジン塩酸塩・1水和物から調製し、クエン酸緩衝液はクエン酸・1水和物及びクエン酸三ナトリウム・2水和物から調製し、表1に記載の組み合わせで、各緩衝液由来の酸成分(リン酸、クエン酸、ヒスチジン)のアダリムマブ水性製剤における濃度(終濃度)が表1に示す濃度となるように配合した。
凝集体量の変化率={[各凍結融解サイクル後の試料における凝集体量(%)]/[凍結融解サイクルゼロの試料における凝集体量(%)]}×100
により、凍結融解前(凍結融解サイクルゼロの試料)に対する凝集体量の変化率(%Change in Aggregate)を求め、凍結融解に対する安定性を評価した。その結果、処方F4~F6はいずれも凍結融解による明らかな凝集体の増加は認められず、極めて安定であった(図3)。
種々の緩衝液を配合した試料(アダリムマブ水性製剤)をそれぞれ調製した(表2)。これらの試料はアダリムマブ50mg/mL、NaCl 6.16mg/mL、マンニトール12mg/mL、ポリソルベート80 1mg/mL、及び表2に示す緩衝液を含有し、pHが5.2~5.5の水溶液として調製した。また、リン酸緩衝液及びヒスチジン緩衝液は上記アダリムマブ水性製剤の調製1と同様に調製し、酢酸緩衝液は酢酸及び酢酸ナトリウム・3水和物から調製し、表2に記載の組み合わせで、各緩衝液由来の酸成分(リン酸、ヒスチジン、酢酸)のアダリムマブ水性製剤における濃度(終濃度)が表2に示す濃度となるように配合した。
Claims (7)
- アダリムマブと、緩衝液としてヒスチジン緩衝液及びリン酸緩衝液とを含み、かつ、pHが5.5~6.1である水性液体製剤である医薬組成物。
- 更に緩衝剤、賦形剤及び等張化剤のうちから選択される少なくとも一つの添加剤を含んでなる請求項1に記載の医薬組成物。
- ヒスチジンの濃度が5mM~50mMである請求項1又は2に記載の医薬組成物。
- リン酸の濃度が1mM~20mMである請求項1~3のうちのいずれか一項に記載の医薬組成物。
- 請求項1~4のうちのいずれか一項に記載の医薬組成物が凍結されてなる凍結製剤である医薬組成物。
- 請求項1~4のうちのいずれか一項に記載の医薬組成物が予備充填滅菌注射器中に保存されている医薬製剤。
- 請求項1~5のうちのいずれか一項に記載の医薬組成物及び請求項6に記載の医薬製剤のうちの少なくとも1つと、前記医薬組成物の仕様説明書とを含むキット製剤。
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KR1020167030439A KR20170018810A (ko) | 2014-06-10 | 2015-06-04 | 안정한 아달리무맙 수성 제제 |
JP2016527771A JPWO2015190378A1 (ja) | 2014-06-10 | 2015-06-04 | 安定なアダリムマブ水性製剤 |
EP15807343.7A EP3156071A4 (en) | 2014-06-10 | 2015-06-04 | Stable aqueous adalimumab preparation |
US15/317,538 US20170189528A1 (en) | 2014-06-10 | 2015-06-04 | Stable aqueous adalimumab formulation |
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EP (1) | EP3156071A4 (ja) |
JP (1) | JPWO2015190378A1 (ja) |
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Cited By (5)
Publication number | Priority date | Publication date | Assignee | Title |
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CN107619442A (zh) * | 2016-07-15 | 2018-01-23 | 上海百迈博制药有限公司 | 一种重组抗TNF‑α全人源单克隆抗体制剂 |
WO2018193471A1 (en) * | 2017-04-18 | 2018-10-25 | Dr. Reddy's Laboratories Limited | Stable liquid pharmaceutical composition |
JP2022526490A (ja) * | 2019-05-17 | 2022-05-25 | 通化▲東▼宝葯▲業▼股▲フン▼有限公司 | 安定なセクキヌマブ注射剤及びその製造方法 |
RU2773747C2 (ru) * | 2017-04-18 | 2022-06-09 | Др. Редди'З Лабораториз Лимитед | Устойчивая жидкая фармацевтическая композиция |
JP2022187025A (ja) * | 2016-10-24 | 2022-12-15 | ノビミューン エスアー | インターフェロンガンマ関連の適応症を処置または予防するための方法、組成物および投薬レジメン |
Families Citing this family (2)
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US20220081478A1 (en) * | 2019-01-11 | 2022-03-17 | Samsung Bioepis Co., Ltd. | Pharmaceutical composition comprising antibody, device comprising same, and use thereof |
EP3714902B1 (en) * | 2020-03-13 | 2024-08-28 | LEK Pharmaceuticals d.d. | Stabilization of pharmaceutical compositions comprising polysorbate |
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JP2012510468A (ja) * | 2008-11-28 | 2012-05-10 | アボット・ラボラトリーズ | 安定な抗体組成物およびこれを安定させるための方法 |
JP2012526121A (ja) * | 2009-05-04 | 2012-10-25 | アボツト・バイオテクノロジー・リミテツド | ヒト抗tnfアルファ抗体の安定した高蛋白質濃度製剤 |
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EP2863951A1 (en) | 2012-06-12 | 2015-04-29 | Boehringer Ingelheim International GmbH | Pharmaceutical formulation for a therapeutic antibody |
HUE049282T2 (hu) | 2012-09-07 | 2020-09-28 | Coherus Biosciences Inc | Adalimumab stabil vizes formulációi |
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- 2015-06-04 WO PCT/JP2015/066136 patent/WO2015190378A1/ja active Application Filing
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JP2012510468A (ja) * | 2008-11-28 | 2012-05-10 | アボット・ラボラトリーズ | 安定な抗体組成物およびこれを安定させるための方法 |
JP2012526121A (ja) * | 2009-05-04 | 2012-10-25 | アボツト・バイオテクノロジー・リミテツド | ヒト抗tnfアルファ抗体の安定した高蛋白質濃度製剤 |
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Cited By (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN107619442A (zh) * | 2016-07-15 | 2018-01-23 | 上海百迈博制药有限公司 | 一种重组抗TNF‑α全人源单克隆抗体制剂 |
CN107619442B (zh) * | 2016-07-15 | 2022-09-20 | 泰州迈博太科药业有限公司 | 一种重组抗TNF-α全人源单克隆抗体制剂 |
JP2022187025A (ja) * | 2016-10-24 | 2022-12-15 | ノビミューン エスアー | インターフェロンガンマ関連の適応症を処置または予防するための方法、組成物および投薬レジメン |
WO2018193471A1 (en) * | 2017-04-18 | 2018-10-25 | Dr. Reddy's Laboratories Limited | Stable liquid pharmaceutical composition |
CN110831621A (zh) * | 2017-04-18 | 2020-02-21 | 雷迪博士实验室有限公司 | 稳定的液体药物组合物 |
RU2773747C2 (ru) * | 2017-04-18 | 2022-06-09 | Др. Редди'З Лабораториз Лимитед | Устойчивая жидкая фармацевтическая композиция |
JP2022526490A (ja) * | 2019-05-17 | 2022-05-25 | 通化▲東▼宝葯▲業▼股▲フン▼有限公司 | 安定なセクキヌマブ注射剤及びその製造方法 |
JP7196333B2 (ja) | 2019-05-17 | 2022-12-26 | 通化▲東▼宝葯▲業▼股▲フン▼有限公司 | 安定なセクキヌマブ注射剤及びその製造方法 |
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EP3156071A1 (en) | 2017-04-19 |
KR20170018810A (ko) | 2017-02-20 |
EP3156071A4 (en) | 2018-01-10 |
JPWO2015190378A1 (ja) | 2017-04-20 |
US20170189528A1 (en) | 2017-07-06 |
TW201613640A (en) | 2016-04-16 |
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