JP5586896B2 - 最終分化を誘導する方法 - Google Patents
最終分化を誘導する方法 Download PDFInfo
- Publication number
- JP5586896B2 JP5586896B2 JP2009188710A JP2009188710A JP5586896B2 JP 5586896 B2 JP5586896 B2 JP 5586896B2 JP 2009188710 A JP2009188710 A JP 2009188710A JP 2009188710 A JP2009188710 A JP 2009188710A JP 5586896 B2 JP5586896 B2 JP 5586896B2
- Authority
- JP
- Japan
- Prior art keywords
- group
- saha
- pharmaceutically acceptable
- pharmaceutical composition
- hdac
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
Links
- 0 CC(N=*[C@](CC(*Cc1ccccc1)=O)C(Nc1cccc2c1nccc2)=*)=O Chemical compound CC(N=*[C@](CC(*Cc1ccccc1)=O)C(Nc1cccc2c1nccc2)=*)=O 0.000 description 5
Images
Classifications
-
- 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
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/4841—Filling excipients; Inactive ingredients
- A61K9/4866—Organic macromolecular compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/13—Amines
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/16—Amides, e.g. hydroxamic acids
- A61K31/164—Amides, e.g. hydroxamic acids of a carboxylic acid with an aminoalcohol, e.g. ceramides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/16—Amides, e.g. hydroxamic acids
- A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
- A61K38/12—Cyclic peptides, e.g. bacitracins; Polymyxins; Gramicidins S, C; Tyrocidins A, B or C
-
- 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
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
- A61K47/38—Cellulose; Derivatives thereof
-
- 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
-
- 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
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/04—Antipruritics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/06—Antipsoriatics
-
- 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
-
- 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
-
- 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
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
- A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
- A61P21/02—Muscle relaxants, e.g. for tetanus or cramps
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- 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]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
- A61P31/18—Antivirals for RNA viruses for HIV
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/04—Antineoplastic agents specific for metastasis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C259/00—Compounds containing carboxyl groups, an oxygen atom of a carboxyl group being replaced by a nitrogen atom, this nitrogen atom being further bound to an oxygen atom and not being part of nitro or nitroso groups
- C07C259/04—Compounds containing carboxyl groups, an oxygen atom of a carboxyl group being replaced by a nitrogen atom, this nitrogen atom being further bound to an oxygen atom and not being part of nitro or nitroso groups without replacement of the other oxygen atom of the carboxyl group, e.g. hydroxamic acids
-
- 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
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1629—Organic macromolecular compounds
- A61K9/1652—Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin
Description
本発明は、2002年3月4日に出願された合衆国仮出願第60/361,759号の利益を主張する。この仮出願の全体の教示は、本明細書に参考として援用される。
本発明は、国立癌研究所によって授与される認可番号1R21 CA 096228−01の下、全部または一部が政府の支持でなされた。政府は、本発明において特定の権利を有し得る。
本発明は、新生物細胞の最終分化、細胞増殖停止および/またはアポトーシスを選択的に誘導すること、および/またはヒストンデアセチラーゼ(HDAC)インヒビターを含む薬学的組成物のHDAC阻害投与の方法を提供する。この薬学的組成物の経口処方物は、高いバイオアベイラビリティーのような好ましい薬物動態学プロフィールを有し、そして驚くべきことに、延長された時間の期間に亘り、活性化合物の高い血中レベルを生じる。
本出願を通じて、種々の刊行物が括弧内のアラビア数字によって参照される。これら刊行物の完全な引用が、特許請求の範囲のすぐ前にある明細書の末端に見出され得る。これら刊行物のそれら全部の開示は、本発明が関係する当該技術分野の状態をより詳細に記載するために、本出願中に参考として本明細書によって援用される。
本発明は、投与の後少なくとも2時間の期間に亘り、被験体においてインビボでヒストンデアセチラーゼを阻害し得る平均血漿濃度のヒストンデアセチラーゼ(HDAC)インヒビターを生成する方法を提供し、これは、上記被験体に、HDACインヒビターまたは薬学的に受容可能なその塩またはその水和物、および薬学的に受容可能なキャリアまたは希釈剤を含む薬学的組成物の有効量を投与する工程を包含する。
以下の構造によって表されるピロキサミド:
本発明は、投与後の少なくとも2時間の期間にわたって、被験体においてインビボでヒストンデアセチラーゼを阻害し得る平均血漿濃度のヒストンデアセチラーゼ(HDAC)を生成する方法を提供し、この方法は、この被験体に、HDACインヒビターまたはその薬学的に受容可能な塩もしくは水和物、および薬学的に受容可能なキャリアまたは希釈剤を含む有効量の薬学的組成物を投与する工程を包含する。
ヒストンデアセチラーゼ(HDAC)は、この用語が本明細書中で使用される場合、ヌクレオソームコアヒストンのアミノ末端テイル中のリジン残基からのアセチル基の除去を触媒する酵素である。それ自体、HDACは、ヒストンアセチルトランスフェラーゼ(HAT)と共に、ヒストンのアセチル化状態を調節する。ヒストンアセチル化は、HDACの遺伝子発現およびインヒビターに影響を与える(例えば、ヒドロキサム酸ベースのハイブリッド極性化合物であるスベロイルアニリドヒドロキサム酸(suberoylanilide hydroxamic acid)(SAHA)は、形質転換した細胞の増殖停止、分化および/またはアポトーシスをインビトロで誘導し、そして腫瘍増殖をインビボで阻害する)。HDACは、構造的相同性に基づいて3つのクラスに分割され得る。クラスI HDAC(HDAC1、2、3および8)は、酵母RPD3タンパク質に対する類似性を保有し、核に位置し、そして転写共リプレッサーと関連して複合体中に見出される。クラスII HDAC(HDAC4、5、6、7および9)は、酵母HDA1タンパク質と類似であり、核および細胞質の両方の細胞内局在を有する。クラスIおよびクラスIIの両方のHDACは、ヒドロキサム酸ベースのHDACインヒビター(例えば、SAHA)によって阻害される。クラスIII HDACは、酵母SIR2タンパク質に関連するNAD依存性酵素の構造的に遠いクラスを形成し、そしてヒドロキサム酸ベースのHDACインヒビターによって阻害されない。
(A.ヒドロキサム誘導体)
例えば、スベロイルアニリドヒドロキサム酸(SAHA)(Richonら、Proc.Natl.Acad.Sci.USA 95,3003−3007(1998));m−カルボキシ桂皮酸ビスヒドロキサミド(CBHA)(Richonら、前出);ピロキサミド;トリコスタチン(trichostatin)アナログ(例えば、トリコスタチンA(TSA)およびトリコスタチンC(Kogheら、1998.Biochem.Pharmacol.56:1359−1364));サリチルヒドロキサム酸(SBHA)(Andrewsら、International J.Parasitology 30,761−768(2000));スベロイルビスヒドロキサム酸(SBHA)(米国特許第5,608,108号);アゼライック(azelaic)ビスヒドロキサム酸(ABHA)(Andrewsら、前出);アゼライック−1−ヒドロキサメート−9−アニリド(AAHA)(Qiuら、Mol.Biol.Cell 11,2069−2083(2000));6−(3−クロロフェニルウレイド)カプロニックヒドロキサム酸(3C1−UCHA);オキサムフラチン[(2E)−5−[3−[(フェニルスルホニル)アミノールフェニル]−ペンタ−2−エン−4−イノヒドロキサム酸](oxamflatin[(2E)−5−[3−[(phenylsufonyl)aminol phenyl]−pent−2−en−4−ynohydroxamic acid])(Kimら、Oncogene,18:2461−2470(1999));A−161906,Scriptaid(Suら、2000 Cancer Research,60:3137−3142);PXD−101(Prolifix);LAQ−824;CHAP;MW2796(Andrewsら、前出);MW2996(Andrewsら、前出);または米国特許第5,369,108号、同第5,932,616号、同第5,700,811号、同第6,087,367号および同第6,511,990号に開示されるようなヒドロキサム酸のいずれか。
例えば、トラポキシン(trapoxin)A(TPX)−環状テトラペプチド(シクロ−(L−フェニルアラニル−L−フェニルアラニル−D−ピペコリニル−L−2−アミノ−8−オキソ−9,10−エポキシデカノイル))(Kijimaら、J Biol.Chem268,22429−22435(1993));FR901228(FK 228,デプシペプチド)(Nakajimaら、Ex.Cell Res.241,126−133(1998));FR225497環状テトラペプチド(H.Moriら、PCT出願WO00/08048(2000年2月17日));アピシジン(apicidin)環状テトラペプチド[シクロ(N−O−メチル−L−トリプトファニル−L−イソロイシニル−D−ピペコリニル−L−2−アミノ−8−オキソデカノイル)](Darkin−Rattrayら、Proc.Natl.Acad.Sci.USA 93,13143−13147(1996));アピシジンIa、アピシジンIb、アピシジンIc、アピシジンIIaおよびアピシジンIIb(P.Dulskiら、PCT出願WO97/11366);CHAP、HC−毒素環状テトラペプチド(Boschら、Plant Cell 7,1941−1950(1995));WF27082環状テトラペプチド(PCT出願WO98/48825);およびクラミドシン(chlamydocin)(Boschら、前出)。
例えば、酪酸ナトリウム(Cousensら、J.Biol.Chem254,1716−1723(1979));イソバレレート(McBainら、Biochem.Pharm.53:1357−1368(1997));バレレート(McBainら、前出);4−フェニルブチレート(4−PBA)(LeaおよびTulsyan,Anticancer Research,15,879−873(1995));フェニルブチレート(PB)(Wangら、Cancer Research,59,2766−2799(1999));プロピオネート(McBainら、前出);ブチルアミド(LeaおよびTulsyan、前出);イソブチルアミド(LeaおよびTulsyan、前出);フェニルアセテート(LeaおよびTulsyan、前出);3−ブロモプロピオネート(LeaおよびTulsyan、前出);トリブチリン(Guanら、Cancer Research,60,749−755(2000));バルプロ酸およびバルプロエート。
例えば、CI−994;MS−27−275[N−(2−アミノフェニル)−4−[N−(ピリジン−3−イルメトキシカルボニル)アミノメチル]ベンズアミド](Saitoら、Proc.Natl.Acad.Sci.USA 96,4592−4597(1999));およびMS−27−275の3’−アミノ誘導体(Saitoら、前出)。
例えば、トリフルオロメチルケトン(Freyら、Bioorganic&Med.Chem.Lett.(2002),12,3443−3447;米国特許第6,511,990号)およびα−ケトアミド(例えば、N−メチル−α−ケトアミド)。
例えば、デプデシン(depudecin)(Kwonら、1998.PNAS 95:3356−3361)。
従って、1実施形態において、本発明は、式1の構造:
式31の構造によって表される化合物:
本発明の化合物、その誘導体、フラグメント、アナログ、ホモログ、薬学的に受容可能な塩または水和物は、経口投与するのに適切な薬学的組成物に薬学的に受容可能なキャリアまたは賦形剤と共に組み込まれ得る。このような組成物は、代表的に、治療有効量の上記の化合物のいずれか、および薬学的に受容可能なキャリアを含む。好ましくは、有効量とは、適切な新生物細胞の末端分化を選択的に誘導するのに有効であり、かつ患者に毒性を引き起こす量よりも小さい量である。
I.他の顕著な神経学的徴候(例えば、アルツハイマー病;アルツハイマー型の老人性痴呆症;およびピック病(脳葉萎縮))の非存在下での進行性痴呆によって特徴付けられる障害。
SAHAは、以下に概説される方法、または米国特許第5,369,108号(この内容は、その全体が参考として援用される)に記載される方法もしくは任意の他の方法に従って、合成され得る。
(工程1−スベルアニリン酸(suberanilic acid)の合成)
粗SAHAを、メタノール/水から再結晶化した。メカニカルスターラー、熱電対、凝縮器および不活性雰囲気のための入口を備えた50Lフラスコに、結晶化させる粗SAHA(2,525.7g)、続いて、2,625mlの脱イオン水および15,755mlのメタノールを入れた。この物質を加熱還流させて、溶液を得た。次いで、5,250mlの脱イオン水をこの反応混合物に添加した。熱を遮断し、そしてこの混合物を、冷却させた。フラスコを安全に操作し得るようにこの混合物を十分に冷却した(28℃)とき、フラスコを熱マントルから除き、そして冷却浴として使用するためにタブに配置した。氷/水をタブに添加して、この混合物を−5℃に冷却した。この混合物を2時間その温度未満に維持した。この生成物を濾過によって単離し、そしてフィルターケーキを、1.5Lの冷メタノール/水(2:1)で洗浄した。漏斗をカバーし、そして生成物を1.75時間、減圧下で部分的に乾燥させた。生成物を漏斗から取り出し、そして6個のガラストレーに配置した。トレーを減圧オーブンに配置し、そして生成物を、減圧供給源としてNashポンプを使用し、そしてアルゴンブリードを使用して、60℃で64.75時間乾燥させた。トレーを秤量のために取り出し、次いで、オーブンに戻し、そしてさらに4時間60℃で乾燥して、一定の重量を得た。第2の乾燥期間の間、減圧供給源は、オイルポンプであり、アルゴンブリードを使用しなかった。この物質を、二重4−ミルポリエチレンバッグに包装し、そしてプラスチック外側容器内に配置した。サンプリング後の最終重量は、2,540.9g(92.5%)であった。
(背景):ハイブリッド極性細胞性分化剤での処置は、ヒト固形腫瘍由来細胞株および移植片の増殖を阻害した。この効果は、一部、ヒストンデアセチラーゼの阻害によって媒介される。SAHAは、実験室および前臨床研究における腫瘍細胞増殖停止、分化およびアポトーシスを誘導する能力を有することが示された強力なヒストンデアセチラーゼインヒビターである。
別の実験において、表4に示されるように、固形腫瘍を有する25人の患者は、アームAに登録され、ホジキンリンパ腫または非ホジキンリンパ腫を有する13人の患者は、アームBに登録され、そして急性白血病を有する1人の患者および骨髄形成異常を有する1人の患者は、アームCに登録された。
コホートIIで処置された11人の患者のうち、1人の患者が、最初の処置サイクルの間、グレード3の下痢およびグレード3の脱水のDLTを経験した。9人の患者が、コホートIIIに入力された。2人の患者は、迅速な疾患の進行に起因して、初期に研究を停止したので、28日毒性評価について評価不可能であった。7人の残りの患者のうち、5人が、最初の処置サイクルの間、DLTを経験した:下痢/脱水(n=1)、疲労/脱水(n=1)、食欲不振(n=1)、脱水(n=1)および食欲不振/脱水(n=1)。これらの5人の患者は、研究薬物を持続した後約1週間で回復した。これらの患者は、後に、400mgQDに減少した用量であり、これは十分に耐えられるようであった。コホートIIIにおける全ての患者について400mgのBIDで中央日は、21日であった。これらの知見に基づいて、400mg q12時間投薬スケジュールは、最大寛容用量を超えていると判断した。プロトコル訂正後、1日1回の600mgの投薬でコホートIVで自然増加(accrual)を続けた。コホートIVに登録された7人の患者のうち、2人が、迅速な疾患の進行に起因して、初期に研究を停止したので、28日毒性評価について評価不可能であった。3人の患者は、最初の処置サイクルの間、DLTを経験した:食欲不振/脱水/疲労(n=1)、および下痢/脱水(n=2)。従って、600mgの用量は、最大の許容用量を超えていると判断し、1日当たり1回400mgの用量は、毎日1回の経口投与について最大の許容用量として規定された。連続的に投与される200mgのBIDおよび300mgのBIDで、1日2回の投薬スケジュールのさらなる用量レベルを評価するために、プロトコルを訂正した。
表5は、静脈内でSAHAを受容する患者についての投薬スケジュールを示す。患者は、コホートIで開始し、300mg/m2のSAHAを、1週間週に5日の連続した日で、合計1500mg/m2の用量を受容する。次いで、患者は、処置が、疾患の進行、腫瘍後退、受容不可能な副作用または他の処置を受けた患者に起因して終了しない限り、2週間の間、観察され、そしてコホートIIに続けられ、次いで、コホートを通じて進めた。
Claims (12)
- 連続的に経口投与される請求項1に記載の薬学的組成物。
- 癌が肺癌である請求項1又は2に記載の薬学的組成物。
- 癌が骨髄腫である請求項1又は2に記載の薬学的組成物。
- 癌がホジキンリンパ腫である請求項1又は2に記載の薬学的組成物。
- 癌が膀胱黒色腫である請求項1又は2に記載の薬学的組成物。
- 癌が腎臓癌腫である請求項1又は2に記載の薬学的組成物。
- 癌が乳房癌腫である請求項1又は2に記載の薬学的組成物。
- 癌が前立腺癌腫である請求項1又は2に記載の薬学的組成物。
- 癌が卵巣癌腫である請求項1又は2に記載の薬学的組成物。
- 癌が結腸直腸癌腫である請求項1又は2に記載の薬学的組成物。
- 組成物がSAHAを含む請求項1又は2に記載の薬学的組成物。
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US36175902P | 2002-03-04 | 2002-03-04 | |
US60/361,759 | 2002-03-04 |
Related Parent Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2003574115A Division JP4732693B2 (ja) | 2002-03-04 | 2003-03-04 | 最終分化を誘導する方法 |
Publications (3)
Publication Number | Publication Date |
---|---|
JP2010001302A JP2010001302A (ja) | 2010-01-07 |
JP2010001302A5 JP2010001302A5 (ja) | 2010-02-18 |
JP5586896B2 true JP5586896B2 (ja) | 2014-09-10 |
Family
ID=27805074
Family Applications (4)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2003574115A Expired - Lifetime JP4732693B2 (ja) | 2002-03-04 | 2003-03-04 | 最終分化を誘導する方法 |
JP2009188712A Expired - Lifetime JP5675071B2 (ja) | 2002-03-04 | 2009-08-17 | 最終分化を誘導する方法 |
JP2009188710A Expired - Lifetime JP5586896B2 (ja) | 2002-03-04 | 2009-08-17 | 最終分化を誘導する方法 |
JP2014146512A Pending JP2014237669A (ja) | 2002-03-04 | 2014-07-17 | 最終分化を誘導する方法 |
Family Applications Before (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2003574115A Expired - Lifetime JP4732693B2 (ja) | 2002-03-04 | 2003-03-04 | 最終分化を誘導する方法 |
JP2009188712A Expired - Lifetime JP5675071B2 (ja) | 2002-03-04 | 2009-08-17 | 最終分化を誘導する方法 |
Family Applications After (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2014146512A Pending JP2014237669A (ja) | 2002-03-04 | 2014-07-17 | 最終分化を誘導する方法 |
Country Status (18)
Country | Link |
---|---|
US (7) | US20040072735A1 (ja) |
EP (4) | EP2082737B1 (ja) |
JP (4) | JP4732693B2 (ja) |
KR (2) | KR100868813B1 (ja) |
CN (3) | CN103393630A (ja) |
AU (1) | AU2003213684C1 (ja) |
BR (1) | BR0308250A (ja) |
CA (3) | CA2671976C (ja) |
ES (1) | ES2532607T3 (ja) |
HK (1) | HK1072362A1 (ja) |
IL (3) | IL163909A0 (ja) |
MX (1) | MXPA04008577A (ja) |
NO (2) | NO329984B1 (ja) |
NZ (3) | NZ567758A (ja) |
PL (1) | PL372239A1 (ja) |
RU (3) | RU2394022C2 (ja) |
WO (1) | WO2003075839A2 (ja) |
ZA (2) | ZA200407942B (ja) |
Families Citing this family (99)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6777217B1 (en) | 1996-03-26 | 2004-08-17 | President And Fellows Of Harvard College | Histone deacetylases, and uses related thereto |
US20030129724A1 (en) | 2000-03-03 | 2003-07-10 | Grozinger Christina M. | Class II human histone deacetylases, and uses related thereto |
US7244853B2 (en) | 2001-05-09 | 2007-07-17 | President And Fellows Of Harvard College | Dioxanes and uses thereof |
AU2002340253C1 (en) * | 2001-10-16 | 2011-03-31 | Sloan-Kettering Institute For Cancer Research | Treatment of neurodegenerative diseases and cancer of the brain |
EP1482962A4 (en) * | 2002-02-15 | 2009-12-23 | Sloan Kettering Inst Cancer | METHOD OF TREATING THIOREDOXIN-MEDIATED DISEASES (TRX) |
US20060276547A1 (en) * | 2002-03-04 | 2006-12-07 | Bacopoulos Nicholas G | Methods of treating cancer with HDAC inhibitors |
US20040132825A1 (en) * | 2002-03-04 | 2004-07-08 | Bacopoulos Nicholas G. | Methods of treating cancer with HDAC inhibitors |
US20070060614A1 (en) * | 2002-03-04 | 2007-03-15 | Bacopoulos Nicholas G | Methods of treating cancer with hdac inhibitors |
EP2082737B1 (en) * | 2002-03-04 | 2014-12-31 | Merck HDAC Research, LLC | Methods of inducing terminal differentiation |
US7456219B2 (en) | 2002-03-04 | 2008-11-25 | Merck Hdac Research, Llc | Polymorphs of suberoylanilide hydroxamic acid |
US7148257B2 (en) | 2002-03-04 | 2006-12-12 | Merck Hdac Research, Llc | Methods of treating mesothelioma with suberoylanilide hydroxamic acid |
TWI319387B (en) | 2002-04-05 | 2010-01-11 | Astrazeneca Ab | Benzamide derivatives |
WO2003088954A1 (en) * | 2002-04-15 | 2003-10-30 | Sloan-Kettering Institute For Cancer Research | Combination therapy for the treatment of cancer |
TW559390U (en) * | 2002-08-27 | 2003-10-21 | Molex Inc | Electrical connector |
FR2847817B1 (fr) * | 2002-11-28 | 2006-11-10 | Centre Nat Rech Scient | Utilisation d'un inhibiteur d'histone deacetylase pour le traitement des dystrophies musculaires |
KR20050122210A (ko) * | 2003-03-17 | 2005-12-28 | 다케다 샌디에고, 인코포레이티드 | 히스톤 탈아세틸화 효소 억제제 |
CN1839121A (zh) * | 2003-04-01 | 2006-09-27 | 斯隆-凯特林癌症研究所 | 异羟肟酸化合物及其使用方法 |
PL1651612T3 (pl) | 2003-07-22 | 2012-09-28 | Astex Therapeutics Ltd | Związki 3,4-pochodne 1h-pirazolu i ich zastosowanie jako kinazy zależne od cyklin (cdk) i modulatory kinazy syntazy glikogenu-3 (gsk-3) |
KR20050022216A (ko) * | 2003-08-25 | 2005-03-07 | 윤덕구 | 동결건조 즉석소면 및 그 제조방법 |
ATE462426T1 (de) * | 2003-08-26 | 2010-04-15 | Merck Hdac Res Llc | Verwendung von saha zur behandlung von mesotheliom |
US20050137234A1 (en) * | 2003-12-19 | 2005-06-23 | Syrrx, Inc. | Histone deacetylase inhibitors |
WO2005065681A1 (en) * | 2003-12-19 | 2005-07-21 | Takeda San Diego, Inc. | N- hydroxy-3-(3-(1h-imidazol-2-yl)-phenyl)-acrylamide derivatives and related compounds as histone deacetylase (hdac) inhibitors for the treatment of cancer |
MX2007001550A (es) * | 2004-08-09 | 2007-04-10 | Astellas Pharma Inc | Compuestos de hidroxiamida que tienen actividad como inhibidores de histona desacetilasa (hdac). |
CN101115495B (zh) * | 2004-12-14 | 2011-06-22 | 生物如恩克斯株式会社 | 通过runx2乙酰化作用增强bmp的骨形成活性的方法 |
US7642275B2 (en) * | 2004-12-16 | 2010-01-05 | Takeda San Diego, Inc. | Histone deacetylase inhibitors |
AU2006207321B2 (en) * | 2005-01-21 | 2012-09-06 | Astex Therapeutics Limited | Pharmaceutical compounds |
US8404718B2 (en) | 2005-01-21 | 2013-03-26 | Astex Therapeutics Limited | Combinations of pyrazole kinase inhibitors |
AR054425A1 (es) | 2005-01-21 | 2007-06-27 | Astex Therapeutics Ltd | Sales de adicion de piperidin 4-il- amida de acido 4-(2,6-dicloro-benzoilamino) 1h-pirazol-3-carboxilico. |
AU2006207322A1 (en) * | 2005-01-21 | 2006-07-27 | Astex Therapeutics Limited | Combinations of pyrazole kinase inhibitors and further antitumor agents |
EP1845973B1 (en) * | 2005-01-21 | 2015-08-12 | Astex Therapeutics Limited | Pharmaceutical compounds |
WO2006082428A2 (en) | 2005-02-03 | 2006-08-10 | Topotarget Uk Limited | Combination therapies using hdac inhibitors |
EP2491926B1 (en) | 2005-03-22 | 2018-05-09 | President and Fellows of Harvard College | Treatment of protein degradation disorders |
WO2006113606A2 (en) * | 2005-04-18 | 2006-10-26 | Johns Hopkins University | Histone deacetylase inhibitors |
EP1715334A1 (fr) * | 2005-04-22 | 2006-10-25 | Adamant Technologies SA | Procédé utilisant un capteur électrochimique et électrodes formant ce capteur |
US20090215800A1 (en) * | 2005-05-05 | 2009-08-27 | Chroma Therapeutics Ltd | Enzyme and Receptor Modulation |
US7642253B2 (en) * | 2005-05-11 | 2010-01-05 | Takeda San Diego, Inc. | Histone deacetylase inhibitors |
PT1901729E (pt) * | 2005-05-13 | 2012-04-30 | Topotarget Uk Ltd | Formulações farmacêuticas de inibidores de hdac |
TWI415603B (zh) * | 2005-05-20 | 2013-11-21 | Merck Sharp & Dohme | 1,8-辛二醯基苯胺羥胺酸(suberoylanilide hydroxamic acid)之調配物及其製配方法 |
EP2229941A1 (en) * | 2005-05-20 | 2010-09-22 | Merck Sharp & Dohme Corp. | Formulations of suberoylanilide hydroxamic acid and methods for producing same |
JP2009501236A (ja) * | 2005-07-14 | 2009-01-15 | タケダ サン ディエゴ インコーポレイテッド | ヒストンデアセチラーゼ阻害剤 |
CA2621560A1 (en) * | 2005-09-07 | 2007-03-15 | Braincells, Inc. | Modulation of neurogenesis by hdac inhibition |
GB0518720D0 (en) * | 2005-09-14 | 2005-10-19 | Hamlet Pharma Ab | Therapeutic combination |
WO2007117272A2 (en) * | 2005-09-30 | 2007-10-18 | The Henry M. Jackson Foundation For The Advancement Of Military Medicine | Methods for treatment of hemorrhagic shock and related disorders |
CA2626679C (en) * | 2005-11-04 | 2011-08-16 | Merck & Co., Inc. | Methods of treating cancers with saha, carboplatin, and paclitaxel and other combination therapies |
WO2007056244A2 (en) * | 2005-11-04 | 2007-05-18 | Merck & Co., Inc. | Methods of using saha and erlotinib for treating cancer |
EP1947936A4 (en) * | 2005-11-04 | 2010-02-10 | Merck & Co Inc | METHOD FOR THE USE OF SAHA AND BORTEZOMIB FOR THE TREATMENT OF CANCER |
AU2006313517B2 (en) | 2005-11-10 | 2013-06-27 | Topotarget Uk Limited | Histone deacetylase (HDAC) inhibitors (PXD101) for the treatment of cancer alone or in combination with chemotherapeutic agent |
CA2630216A1 (en) * | 2005-11-18 | 2007-05-31 | Gloucester Pharmaceuticals, Inc. | Metabolite derivatives of the hdac inhibitor fk228 |
EP1960384A4 (en) * | 2005-12-05 | 2010-03-24 | Astrazeneca Ab | NOVEL PROCESS FOR THE PRODUCTION OF NON-SALINE ESOMEPRAZOLE |
US20070207950A1 (en) * | 2005-12-21 | 2007-09-06 | Duke University | Methods and compositions for regulating HDAC6 activity |
JP2009525955A (ja) * | 2006-01-13 | 2009-07-16 | タケダ サン ディエゴ インコーポレイテッド | ヒストンデアセチラーゼ阻害剤 |
CN101400362B (zh) | 2006-02-14 | 2016-10-12 | 哈佛大学校长及研究员协会 | 双官能组蛋白去乙酰化酶抑制剂 |
MX2008010462A (es) | 2006-02-14 | 2009-04-17 | Harvard College | Inhibidores de histona desacetilasa. |
US20100137239A1 (en) * | 2006-04-24 | 2010-06-03 | Gloucester Pharmaceuticals | Gemcitabine combination therapy |
CA2654540C (en) * | 2006-05-03 | 2017-01-17 | President And Fellows Of Harvard College | Histone deacetylase and tubulin deacetylase inhibitors |
WO2007129062A1 (en) * | 2006-05-08 | 2007-11-15 | Astex Therapeutics Limited | Pharmaceutical combinations of diazole derivatives for cancer treatment |
EP2018366A4 (en) * | 2006-05-16 | 2010-08-04 | Univ Mcgill | HYBRID MOLECULES HAVING MIXED PROPERTIES OF VITAMIN D RECEPTOR AGONISM AND HISTONE DEACETYLASE INHIBITOR |
US8957027B2 (en) * | 2006-06-08 | 2015-02-17 | Celgene Corporation | Deacetylase inhibitor therapy |
CA2663569A1 (en) * | 2006-09-28 | 2008-04-03 | Merck & Co., Inc. | Pharmaceutical compositions of hdac inhibitors and chelatable metal compounds, and metal-hdac inhibitor chelate complexes |
CA2668070A1 (en) * | 2006-10-30 | 2008-05-08 | Chroma Therapeutics Ltd. | Hydroxamates as inhibitors of histone deacetylase |
EP2086323A4 (en) * | 2006-11-03 | 2010-01-06 | Univ Maryland | METHOD OF USE OF SAHA AND BORTEZOMIB FOR THE TREATMENT OF MULTIPLE MYELOMA |
WO2008083288A2 (en) * | 2006-12-29 | 2008-07-10 | Gloucester Pharmaceuticals | Purifiction of romidepsin |
EP2815761A1 (en) * | 2006-12-29 | 2014-12-24 | Celgene Corporation | Romidepsin-based treatments for cancer |
EP2124916A1 (en) * | 2007-02-27 | 2009-12-02 | Government of the United States of America, as represented by the Secretary, Department of Health and Human Services | Use of histone deacetylase inhibitors for the treatment of central nervous system metastases |
CA2700173C (en) * | 2007-09-25 | 2016-10-11 | Topotarget Uk Limited | Methods of synthesis of certain hydroxamic acid compounds |
RS52343B (en) * | 2007-12-20 | 2012-12-31 | Pharma Mar S.A. | ANTITUMOR UNITS |
PT2262493E (pt) * | 2008-03-07 | 2015-06-02 | Topotarget As | Métodos de tratamento empregando infusão contínua prolongada de belinostat |
RU2515611C2 (ru) | 2008-07-23 | 2014-05-20 | Президент Энд Феллоуз Оф Гарвард Колледж | Ингибиторы деацетилазы и их применение |
NZ592686A (en) | 2008-10-15 | 2012-12-21 | Generics Uk Ltd | Process for the preparation of vorinostat from aniline, hydroxylamine and suberic acid starting materials |
CN102282126A (zh) | 2008-11-26 | 2011-12-14 | 基因里克斯(英国)有限公司 | 多晶型物 |
GB0900555D0 (en) * | 2009-01-14 | 2009-02-11 | Topotarget As | New methods |
EP2236503B1 (en) | 2009-04-03 | 2014-02-26 | NatureWise Biotech & Medicals Corporation | Cinamic compounds and derivatives therefrom for the inhibition of histone deacetylase |
US7994357B2 (en) * | 2009-04-03 | 2011-08-09 | Naturewise Biotech & Medicals Corporation | Cinamic compounds and derivatives therefrom for the inhibition of histone deacetylase |
EP2277387B1 (en) | 2009-07-22 | 2016-10-19 | NatureWise Biotech & Medicals Corporation | New use of histone deacetylase inhibitors in changing mrjp3 protein in royal jelly |
WO2011019393A2 (en) | 2009-08-11 | 2011-02-17 | President And Fellows Of Harvard College | Class- and isoform-specific hdac inhibitors and uses thereof |
JP2013508458A (ja) | 2009-10-26 | 2013-03-07 | ラモット・アット・テル−アヴィヴ・ユニヴァーシティ・リミテッド | Ftsとhdac阻害剤との組合せを用いたがん治療 |
WO2011084623A1 (en) | 2009-12-16 | 2011-07-14 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Method of sensitizing cancer cells to the cytotoxic effects of death receptor ligands in cancer treatment |
US20110195400A1 (en) * | 2010-02-10 | 2011-08-11 | Selinfreund Richard H | Systems and methods for diagnosing cancer |
WO2011127467A1 (en) * | 2010-04-09 | 2011-10-13 | Companion Diagnostics, Inc. | Devices, systems, and methods for biomarker stabilization |
MX2012012695A (es) | 2010-05-05 | 2013-02-26 | Teva Womens Health Inc | Metodos para reducir sintomas en sujetos utilizando formas de dosificacion individuales con velocidades de liberacion que disminuyen gradualmente. |
ES2755909T3 (es) | 2010-07-12 | 2020-04-24 | Celgene Corp | Formas sólidas de la romidepsina y sus usos |
US8859502B2 (en) | 2010-09-13 | 2014-10-14 | Celgene Corporation | Therapy for MLL-rearranged leukemia |
DK2624832T3 (en) * | 2010-10-08 | 2018-01-08 | Vib Vzw | HDAC INHIBITORS FOR TREATMENT OF CHARCOT-MARIE-TOOTHS DISEASE |
US20120164674A1 (en) * | 2010-10-28 | 2012-06-28 | Selinfreund Richard H | Devices and washes for biomarker stabilization |
EP3750544A3 (en) | 2011-11-30 | 2021-03-24 | Emory University | Jak inhibitors for use in the prevention or treatment of viral infection |
CN102793693A (zh) * | 2012-09-07 | 2012-11-28 | 天津医科大学 | 伏立诺他在制备治疗自身免疫及炎症性疾病药物方面的应用 |
AU2013202506B2 (en) | 2012-09-07 | 2015-06-18 | Celgene Corporation | Resistance biomarkers for hdac inhibitors |
AU2013202507B9 (en) | 2012-11-14 | 2015-08-13 | Celgene Corporation | Inhibition of drug resistant cancer cells |
EP2968565A2 (en) | 2013-03-14 | 2016-01-20 | Genentech, Inc. | Methods of treating cancer and preventing cancer drug resistance |
NZ630311A (en) | 2013-12-27 | 2016-03-31 | Celgene Corp | Romidepsin formulations and uses thereof |
CN103819364B (zh) * | 2014-01-24 | 2015-12-02 | 中南大学 | N-烃酰基环内酰胺衍生物的一锅合成方法 |
CN107405321A (zh) | 2015-01-23 | 2017-11-28 | 坦普尔大学 | 短链脂肪酸在癌症预防中的应用 |
WO2016164392A1 (en) | 2015-04-06 | 2016-10-13 | The Johns Hopkins University | A h3t3a mutant protein efficiently reduces h3t3p and causes increased cell death of rapidly dividing cells |
CN105055386A (zh) * | 2015-08-12 | 2015-11-18 | 天津医科大学总医院 | 伏立诺他用于制备免疫调节药物的应用 |
CN106187818B (zh) * | 2016-06-27 | 2017-12-08 | 刘美新 | 一种制备抗癌药物伏立诺他的方法 |
US11065217B2 (en) | 2017-01-27 | 2021-07-20 | Temple University—Of the Commonwealth System of Higher Education | Use of short chain fatty acids for the treatment and prevention of diseases and disorders |
CN110891982B (zh) | 2017-04-17 | 2023-12-22 | 芝加哥大学 | 向肠道递送短链脂肪酸以用于人体保健和疾病治疗的聚合物材料 |
US11453661B2 (en) | 2019-09-27 | 2022-09-27 | Takeda Pharmaceutical Company Limited | Heterocyclic compound |
US11583521B2 (en) * | 2020-07-01 | 2023-02-21 | Jubilant Pharma Holdings Inc. | Long-acting injection dosage form of beta 3 adrenoreceptor agonists |
Family Cites Families (66)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CA622801A (en) | 1961-06-27 | L. Clark Robert | Substituted benzimidazolones | |
FR901228A (fr) | 1943-01-16 | 1945-07-20 | Deutsche Edelstahlwerke Ag | Système d'aimant à entrefer annulaire |
DE2460689C3 (de) * | 1974-12-20 | 1980-06-26 | Klinge Pharma Gmbh & Co, 8000 Muenchen | 13-disubstituierte Propanol-(2)-Derivate, Verfahren zu ihrer Herstellung und ihre Verwendung als Arzneimittel |
US4522811A (en) | 1982-07-08 | 1985-06-11 | Syntex (U.S.A.) Inc. | Serial injection of muramyldipeptides and liposomes enhances the anti-infective activity of muramyldipeptides |
JPS61176523A (ja) * | 1985-01-30 | 1986-08-08 | Teruhiko Beppu | 制癌剤 |
JPS61251649A (ja) * | 1985-04-05 | 1986-11-08 | Mitsubishi Petrochem Co Ltd | ジカルボン酸ジアニリドの製造法 |
US5055608A (en) | 1988-11-14 | 1991-10-08 | Sloan-Kettering Institute For Cancer Research | Novel potent inducers of thermal differentiation and method of use thereof |
US5175191A (en) | 1988-11-14 | 1992-12-29 | Sloan-Kettering Institute For Cancer Research | Potent inducers of terminal differentiation and methods of use thereof |
US5608108A (en) | 1988-11-14 | 1997-03-04 | Sloan-Kettering Institute For Cancer Research | Potent inducers of terminal differentiation and method of use thereof |
US5369108A (en) | 1991-10-04 | 1994-11-29 | Sloan-Kettering Institute For Cancer Research | Potent inducers of terminal differentiation and methods of use thereof |
US5700811A (en) | 1991-10-04 | 1997-12-23 | Sloan-Kettering Institute For Cancer Research | Potent inducers of terminal differentiation and method of use thereof |
USRE38506E1 (en) * | 1991-10-04 | 2004-04-20 | Sloan-Kettering Institute For Cancer Research | Potent inducers of terminal differentiation and methods of use thereof |
US5635532A (en) * | 1991-10-21 | 1997-06-03 | The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services | Compositions and methods for therapy and prevention of pathologies including cancer, AIDS and anemia |
HU217629B (hu) | 1991-12-12 | 2000-03-28 | Novartis Ag. | Eljárás fluvasztatint tartalmazó stabilizált gyógyszerkészítmények előállítására |
CA2231251A1 (en) | 1995-09-20 | 1997-03-27 | Merck & Co., Inc. | Histone deacetylase as target for antiprotozoal agents |
US6239178B1 (en) * | 1996-05-17 | 2001-05-29 | George Dimelow Alexander Lord | Method of treating mammals |
US6030961A (en) | 1997-03-11 | 2000-02-29 | Bar-Ilan Research & Development Co., Ltd. | Oxyalkylene phosphate compounds and uses thereof |
US6043389A (en) * | 1997-03-11 | 2000-03-28 | Mor Research Applications, Ltd. | Hydroxy and ether-containing oxyalkylene esters and uses thereof |
US6124495A (en) | 1997-03-11 | 2000-09-26 | Beacon Laboratories, Inc. | Unsaturated oxyalkylene esters and uses thereof |
JPH10262694A (ja) | 1997-03-28 | 1998-10-06 | Sumitomo Forestry Co Ltd | B細胞性リンパ腫の骨髄転移検査法 |
US6387673B1 (en) | 1997-05-01 | 2002-05-14 | The Salk Institute For Biological Studies | Compounds useful for the modulation of processes mediated by nuclear hormone receptors, methods for the identification and use of such compounds |
US6231880B1 (en) * | 1997-05-30 | 2001-05-15 | Susan P. Perrine | Compositions and administration of compositions for the treatment of blood disorders |
AUPO721997A0 (en) | 1997-06-06 | 1997-07-03 | Queensland Institute Of Medical Research, The | Anticancer compounds |
US6262116B1 (en) * | 1998-01-23 | 2001-07-17 | Sloan-Kettering Institute For Cancer Research | Transcription therapy for cancers |
DK1051187T3 (da) | 1998-01-30 | 2004-03-08 | Univ New York | Behandling af follikulære lymfomer ved anvendelse af inhibitorer af lymfotoxin(LT)-syntesevejen |
AUPP505798A0 (en) | 1998-08-04 | 1998-08-27 | Fujisawa Pharmaceutical Co., Ltd. | Novel compound fr225497 substance |
NZ510504A (en) * | 1998-09-25 | 2003-09-26 | Warner Lambert Co | Chemotherapy of cancer with acetyldinaline in combination with gemcitabine, capecitabine or cisplatin |
CZ20011342A3 (cs) | 1998-10-13 | 2001-09-12 | Fujisawa Pharmaceutical Co., Ltd. | Cyklické tetrapeptidy |
AU6718200A (en) | 1999-05-03 | 2000-12-12 | Methylgene, Inc. | Inhibition of histone deacetylase |
US6450992B1 (en) | 1999-07-02 | 2002-09-17 | Smith & Nephew, Inc. | Cannula interface |
JP2001081031A (ja) | 1999-08-30 | 2001-03-27 | Schering Ag | 溶解性および経口吸収性を改善したベンズアミド誘導体含有製剤 |
PL200861B1 (pl) * | 1999-09-08 | 2009-02-27 | Sloan Kettering Inst Cancer | Pochodna kwasu suberynowego, jej zastosowanie i kompozycja farmaceutyczna |
US6673564B2 (en) | 1999-10-18 | 2004-01-06 | Millennium Pharmaceuticals, Inc. | Methods for using 22045, a human cyclic nucleotide phosphodiesterase |
KR20020070285A (ko) | 1999-11-23 | 2002-09-05 | 메틸진, 인크. | 히스톤 디아세틸라제의 억제제 |
AU2001248701A1 (en) | 2000-03-24 | 2001-10-03 | Methylgene, Inc. | Inhibitors of histone deacetylase |
AU2001285042A1 (en) | 2000-08-18 | 2002-03-04 | The Governement Of The United States Of America, Represented By The Secretary, Department Of Health And Human Services | Methods of treating cutaneous and peripheral t-cell lymphoma by a histone deacetylase inhibitor |
PE20020354A1 (es) | 2000-09-01 | 2002-06-12 | Novartis Ag | Compuestos de hidroxamato como inhibidores de histona-desacetilasa (hda) |
AU2001287157A1 (en) * | 2000-09-12 | 2002-03-26 | Virginia Commonwealth University | Promotion of adoptosis in cancer cells by co-administration of cyclin dependent kinase inhibitors and cellular differentiation agents |
GB0023983D0 (en) | 2000-09-29 | 2000-11-15 | Prolifix Ltd | Therapeutic compounds |
AU9013101A (en) | 2000-09-29 | 2002-04-22 | Prolifix Ltd | Carbamic acid compounds comprising a sulfonamide linkage as hdac inhibitors |
AU2002243231A1 (en) * | 2000-11-21 | 2002-07-24 | Wake Forest University | Method of treating autoimmune diseases |
AR035659A1 (es) | 2000-12-07 | 2004-06-23 | Hoffmann La Roche | Hidroxiamidas de acido (1-oxo-1,2,3,4-tetrahidro-naftalen-2-il)-alcanoico, proceso para la manufactura de estos compuestos, composiciones farmaceuticas que contienen dichos compuestos y los usos de los mismos |
US6533803B2 (en) * | 2000-12-22 | 2003-03-18 | Advanced Medical Applications, Inc. | Wound treatment method and device with combination of ultrasound and laser energy |
WO2002060430A1 (en) * | 2001-02-01 | 2002-08-08 | Cornell Research Foundation, Inc. | Use of retinoids plus histone deacetylase inhibitors to inhibit the growth of solid tumors |
US7314953B2 (en) * | 2001-03-27 | 2008-01-01 | Errant Gene Therapeutics, Llc | Treatment of lung cells with histone deacetylase inhibitors |
US6495719B2 (en) * | 2001-03-27 | 2002-12-17 | Circagen Pharmaceutical | Histone deacetylase inhibitors |
US6905669B2 (en) * | 2001-04-24 | 2005-06-14 | Supergen, Inc. | Compositions and methods for reestablishing gene transcription through inhibition of DNA methylation and histone deacetylase |
CA2450129A1 (en) * | 2001-06-14 | 2002-12-27 | Donald G. Jackson | Novel human histone deacetylases |
ITMI20011733A1 (it) | 2001-08-07 | 2003-02-07 | Italfarmaco Spa | Derivati dell'acido idrossamico inibitori degli enzimi istone deacetilasi, quali nuovi farmaci antiinfiammatori inibenti la sintesi di citoc |
AU2002340253C1 (en) * | 2001-10-16 | 2011-03-31 | Sloan-Kettering Institute For Cancer Research | Treatment of neurodegenerative diseases and cancer of the brain |
US20040132643A1 (en) * | 2002-01-09 | 2004-07-08 | Fojo Antonio Tito | Histone deacelylase inhibitors in diagnosis and treatment of thyroid neoplasms |
EP1482962A4 (en) * | 2002-02-15 | 2009-12-23 | Sloan Kettering Inst Cancer | METHOD OF TREATING THIOREDOXIN-MEDIATED DISEASES (TRX) |
US20060276547A1 (en) * | 2002-03-04 | 2006-12-07 | Bacopoulos Nicholas G | Methods of treating cancer with HDAC inhibitors |
EP2082737B1 (en) | 2002-03-04 | 2014-12-31 | Merck HDAC Research, LLC | Methods of inducing terminal differentiation |
US20040132825A1 (en) * | 2002-03-04 | 2004-07-08 | Bacopoulos Nicholas G. | Methods of treating cancer with HDAC inhibitors |
US20070060614A1 (en) * | 2002-03-04 | 2007-03-15 | Bacopoulos Nicholas G | Methods of treating cancer with hdac inhibitors |
US7456219B2 (en) * | 2002-03-04 | 2008-11-25 | Merck Hdac Research, Llc | Polymorphs of suberoylanilide hydroxamic acid |
US7148257B2 (en) * | 2002-03-04 | 2006-12-12 | Merck Hdac Research, Llc | Methods of treating mesothelioma with suberoylanilide hydroxamic acid |
WO2003088954A1 (en) * | 2002-04-15 | 2003-10-30 | Sloan-Kettering Institute For Cancer Research | Combination therapy for the treatment of cancer |
CN1839121A (zh) * | 2003-04-01 | 2006-09-27 | 斯隆-凯特林癌症研究所 | 异羟肟酸化合物及其使用方法 |
ATE462426T1 (de) * | 2003-08-26 | 2010-04-15 | Merck Hdac Res Llc | Verwendung von saha zur behandlung von mesotheliom |
CN102349927A (zh) * | 2003-08-29 | 2012-02-15 | Hdac默克研究有限责任公司 | 联合治疗癌症的方法 |
US20090227674A1 (en) | 2005-08-18 | 2009-09-10 | Richon Victoria M | Combination methods fo saha and targretin for treating cancer |
CA2626679C (en) | 2005-11-04 | 2011-08-16 | Merck & Co., Inc. | Methods of treating cancers with saha, carboplatin, and paclitaxel and other combination therapies |
WO2007056244A2 (en) * | 2005-11-04 | 2007-05-18 | Merck & Co., Inc. | Methods of using saha and erlotinib for treating cancer |
EP1947936A4 (en) * | 2005-11-04 | 2010-02-10 | Merck & Co Inc | METHOD FOR THE USE OF SAHA AND BORTEZOMIB FOR THE TREATMENT OF CANCER |
-
2003
- 2003-03-04 EP EP20090005103 patent/EP2082737B1/en not_active Expired - Lifetime
- 2003-03-04 MX MXPA04008577A patent/MXPA04008577A/es active IP Right Grant
- 2003-03-04 CA CA2671976A patent/CA2671976C/en not_active Expired - Lifetime
- 2003-03-04 EP EP03711372A patent/EP1487426B1/en not_active Revoked
- 2003-03-04 NZ NZ567758A patent/NZ567758A/en not_active IP Right Cessation
- 2003-03-04 KR KR1020077003262A patent/KR100868813B1/ko active IP Right Grant
- 2003-03-04 RU RU2007112879A patent/RU2394022C2/ru active
- 2003-03-04 US US10/379,149 patent/US20040072735A1/en not_active Abandoned
- 2003-03-04 PL PL37223903A patent/PL372239A1/xx unknown
- 2003-03-04 ES ES09005103.8T patent/ES2532607T3/es not_active Expired - Lifetime
- 2003-03-04 JP JP2003574115A patent/JP4732693B2/ja not_active Expired - Lifetime
- 2003-03-04 CN CN2013102683183A patent/CN103393630A/zh active Pending
- 2003-03-04 CA CA 2478094 patent/CA2478094C/en not_active Expired - Lifetime
- 2003-03-04 WO PCT/US2003/006451 patent/WO2003075839A2/en active IP Right Grant
- 2003-03-04 NZ NZ55018503A patent/NZ550185A/xx not_active IP Right Cessation
- 2003-03-04 CA CA 2632078 patent/CA2632078C/en not_active Expired - Lifetime
- 2003-03-04 EP EP20100183586 patent/EP2322160A1/en not_active Withdrawn
- 2003-03-04 CN CNA038095890A patent/CN1720034A/zh active Pending
- 2003-03-04 IL IL16390903A patent/IL163909A0/xx unknown
- 2003-03-04 BR BR0308250A patent/BR0308250A/pt not_active Application Discontinuation
- 2003-03-04 AU AU2003213684A patent/AU2003213684C1/en active Active
- 2003-03-04 RU RU2004133675A patent/RU2320331C2/ru active Protection Beyond IP Right Term
- 2003-03-04 EP EP20100184834 patent/EP2266552A3/en not_active Withdrawn
- 2003-03-04 NZ NZ535578A patent/NZ535578A/en not_active IP Right Cessation
- 2003-03-04 KR KR1020087010088A patent/KR100892016B1/ko active IP Right Grant
- 2003-03-04 CN CN2008100838935A patent/CN101259120B/zh not_active Expired - Lifetime
- 2003-07-09 US US10/616,649 patent/US7399787B2/en active Active
- 2003-09-16 US US10/665,079 patent/US20040127523A1/en not_active Abandoned
-
2004
- 2004-03-01 ZA ZA200407942A patent/ZA200407942B/xx unknown
- 2004-09-05 IL IL16390904A patent/IL163909A/en not_active IP Right Cessation
- 2004-09-28 NO NO20044112A patent/NO329984B1/no not_active IP Right Cessation
-
2005
- 2005-05-25 HK HK05104380A patent/HK1072362A1/xx not_active IP Right Cessation
-
2006
- 2006-02-23 ZA ZA200601757A patent/ZA200601757B/en unknown
-
2007
- 2007-09-11 US US11/853,700 patent/US7732490B2/en active Active
- 2007-11-09 US US11/983,469 patent/US20080114069A1/en not_active Abandoned
-
2009
- 2009-03-12 IL IL197582A patent/IL197582A/en active IP Right Grant
- 2009-07-20 NO NO20092714A patent/NO332749B1/no not_active IP Right Cessation
- 2009-08-17 JP JP2009188712A patent/JP5675071B2/ja not_active Expired - Lifetime
- 2009-08-17 JP JP2009188710A patent/JP5586896B2/ja not_active Expired - Lifetime
-
2010
- 2010-03-09 RU RU2010108448/15A patent/RU2530648C2/ru active
- 2010-04-23 US US12/799,368 patent/US8067472B2/en not_active Expired - Fee Related
-
2011
- 2011-10-19 US US13/276,710 patent/US20120041067A1/en not_active Abandoned
-
2014
- 2014-07-17 JP JP2014146512A patent/JP2014237669A/ja active Pending
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP5586896B2 (ja) | 最終分化を誘導する方法 | |
JP4338734B2 (ja) | Hdac阻害剤による癌処置法 | |
US7148257B2 (en) | Methods of treating mesothelioma with suberoylanilide hydroxamic acid | |
US7456219B2 (en) | Polymorphs of suberoylanilide hydroxamic acid | |
JP2007509171A (ja) | Hdac阻害剤による癌治療法 | |
AU2007203525C1 (en) | Methods of Inducing Terminal Differentiation | |
Richon et al. | Methods of treating Hodgkin's and non-Hodgkin's lymphoma | |
KR20050020760A (ko) | 말단 분화의 유도 방법 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20091214 |
|
A711 | Notification of change in applicant |
Free format text: JAPANESE INTERMEDIATE CODE: A711 Effective date: 20111116 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A821 Effective date: 20111116 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20120410 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20120705 |
|
A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20120710 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20121009 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20130306 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20130604 |
|
A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20130607 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20130704 |
|
A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20130709 |
|
A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20131126 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20140326 |
|
A911 | Transfer to examiner for re-examination before appeal (zenchi) |
Free format text: JAPANESE INTERMEDIATE CODE: A911 Effective date: 20140515 |
|
TRDD | Decision of grant or rejection written | ||
A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20140624 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20140723 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 5586896 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
EXPY | Cancellation because of completion of term |