JP2009536173A - グルタドン - Google Patents
グルタドン Download PDFInfo
- Publication number
- JP2009536173A JP2009536173A JP2009508253A JP2009508253A JP2009536173A JP 2009536173 A JP2009536173 A JP 2009536173A JP 2009508253 A JP2009508253 A JP 2009508253A JP 2009508253 A JP2009508253 A JP 2009508253A JP 2009536173 A JP2009536173 A JP 2009536173A
- Authority
- JP
- Japan
- Prior art keywords
- combination preparation
- pharmaceutical combination
- cancer
- glutaminase
- don
- 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.)
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- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
- A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid
- A61K31/198—Alpha-amino acids, e.g. alanine or edetic acid [EDTA]
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- A—HUMAN NECESSITIES
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Abstract
Description
第二の作用物質b)DONは、1受容体に対して、作用物質a)と組み合わせて、50〜300mg/m2(体表受容体当たりのミリグラム)、有利に70〜250mg/m2、更に有利に75〜220mg/m2、更に有利に80〜200mg/m2、更に有利に90〜185mg/m2、更に有利に100〜170mg/m2、更に有利に110〜160mg/m2、更に有利に120〜150mg/m2、最も有利に130〜140mg/m2の投与量で含有されている。上記値は、1投与単位中に含有される量に相応する。
実施例1:
第I/IIa相臨床試験(GlutaDON(R))において、合計で58名の進行癌患者を、上記の双方の作用物質の組合せ物を用いて治療した。ここで、患者にPEG−PGA 120I.U./m2を1週間に2回静脈内に投与した(注射時間15分間)。これに引き続き、PEG−PGA投与後に、この場合それぞれ2〜4時間後に、DONを、DON 5〜185mg/m2の濃度で静脈内に投与した。注射時間は同様に15分間であった。
GlutaDON(R)試験において、58名の患者を、1週間に2回、PEG−PGA 120I.U./m2を用いて治療した。6週間の期間にわたり、グルタミン含有量が出発値との比で、各患者においてどのような挙動を示すか試験した。全体として、グルタミン含有量は全期間にわたって出発値の10%未満(その上更に、大部分は5%未満)のままであった。従って、使用した濃度(120I.U./m2、1週間に2回)における使用したグルタミナーゼ(PEG−PGA)は、本発明により使用するのに好適である。
Claims (18)
- 癌治療のための製薬学的組合せ調剤において、組合せ調剤が作用物質
a)グルタミナーゼ、及び
b)6−ジアゾ−5−オキソ−L−ノルロイシン(DON)
を含み、ここで、作用物質b)は受容体に対して50〜300mg/m2の投与量で含有されていることを特徴とする製薬学的組合せ調剤。 - 作用物質a)がグルタミナーゼ−アスパラギナーゼである、請求項1記載の製薬学的組合せ調剤。
- 作用物質a)がシュードモナス7Aのグルタミナーゼ−アスパラギナーゼである、請求項1又は2記載の製薬学的組合せ調剤。
- 作用物質a)が変性されており、かつ/又は作用物質a)に1種以上の保護物質が付与されている、請求項1から3までのいずれか1項記載の製薬学的組合せ調剤。
- 作用物質a)が受容体に対して20I.U./m2〜400I.U./m2(体表受容体当たりの国際単位)の濃度で組合せ調剤中に含有されている、請求項1から4までのいずれか1項記載の製薬学的組合せ調剤。
- 作用物質a)を1週間に3回から4週間おきに1回投与することが予定されている、請求項1から5までのいずれか1項記載の製薬学的組合せ調剤。
- 作用物質b)DONが70〜250mg/m2(体表受容体当たりのミリグラム)の濃度で含有されている、請求項1から6までのいずれか1項記載の製薬学的組合せ調剤。
- 作用物質b)を1週間に4回から2週間おきに1回投与することが予定されている、請求項1から7までのいずれか1項記載の製薬学的組合せ調剤。
- 作用物質a)及びb)が一緒の投与単位内に存在している、請求項1から8までのいずれか1項記載の製薬学的組合せ調剤。
- 作用物質a)及びb)が2つの別個の投与単位
作用物質a)を含むA)、及び
作用物質b)を含むB)
内に存在している、請求項1から8までのいずれか1項記載の製薬学的組合せ調剤。 - 少なくとも1つの投与単位が注射可能な形で存在している、請求項1から10までのいずれか1項記載の製薬学的組合せ調剤。
- 少なくとも1つの投与単位を静脈内投与することが予定されている、請求項1から11までのいずれか1項記載の製薬学的組合せ調剤。
- 少なくとも1つの投与単位を経口投与することが予定されている、請求項1から12までのいずれか1項記載の製薬学的組合せ調剤。
- 癌の治療のための製薬学的組合せ調剤を製造するための、a)グルタミナーゼ及びb)6−ジアゾ−5−オキソ−L−ノルロイシン(DON)の使用。
- 6−ジアゾ−5−オキソ−L−ノルロイシンを50〜300mg/m2の投与量で使用する、請求項14記載の使用。
- 製造された製薬学的組合せ調剤が2つの別個の投与単位
作用物質a)を含むA)、及び
作用物質b)を含むB)
を含む、請求項14又は15記載の使用。 - 受容体において提供されるグルタミン含有量が低いレベルに、有利に出発値の30質量%未満に、更に有利に出発値の10%未満に低下されている場合に、投与単位A)の後に投与単位B)を投与することが予定されている、請求項16記載の使用。
- 治療すべき癌が、肺癌、大腸癌、腎臓癌、卵巣癌、乳癌及び前立腺癌から選択されている、請求項14から17までのいずれか1項記載の使用。
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PCT/EP2007/004168 WO2007128588A2 (de) | 2006-05-10 | 2007-05-10 | Glutadon |
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EP (1) | EP2015743B1 (ja) |
JP (1) | JP2009536173A (ja) |
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WO2014043633A1 (en) | 2012-09-17 | 2014-03-20 | Agios Pharmaceuticals, Inc. | Use of e-cadherin and vimentin for selection of treatment responsive patients |
US20160022708A1 (en) * | 2013-03-14 | 2016-01-28 | St. Jude Children's Research Hospital | Methods and compositions for the treatment of glutamine-addicted cancers |
ES2833576T3 (es) | 2014-01-06 | 2021-06-15 | Rhizen Pharmaceuticals S A | Inhibidores de glutaminasa novedosos |
CA2994256A1 (en) * | 2015-07-31 | 2017-02-09 | The Johns Hopkins University | Methods and compositions for treating metabolic reprogramming disorders |
HRP20231163T1 (hr) | 2015-07-31 | 2024-03-15 | The Johns Hopkins University | Prolijekovi glutaminskih analoga |
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2007
- 2007-05-10 AU AU2007247321A patent/AU2007247321B2/en not_active Ceased
- 2007-05-10 EP EP07725088.4A patent/EP2015743B1/de not_active Not-in-force
- 2007-05-10 US US12/300,209 patent/US8465736B2/en not_active Expired - Fee Related
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- 2007-05-10 JP JP2009508253A patent/JP2009536173A/ja active Pending
- 2007-05-10 CA CA002651691A patent/CA2651691A1/en not_active Abandoned
Non-Patent Citations (3)
Title |
---|
JPN5009008716; McGregor,W.G. et al.: 'Glutaminase enhances therapeutic effectiveness of glutamine antimetabolites against human and murine' Proc. Ame. Assoc. Cancer Res. Vol.30, 198903, P.578 * |
JPN5009008717; UNGER,C.: 'Phase I dose escalating study of PEG-PGA and DON (GlutaDON): Anew amino acid depleting anti cancer d' J. Clin. Oncol. Vol.22,No.14S, 20040715, P.3175 * |
JPN5009008718; Unger,C. et al.: 'Phase I dose escalating study of PEG-PGA and DON: Anew amino acid depleting anti cancer drug approac' J. Clin. Oncol. Vol.23, No.16S, 20050601, P.3130 * |
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AU2007247321A1 (en) | 2007-11-15 |
CA2651691A1 (en) | 2007-11-15 |
AU2007247321B2 (en) | 2013-06-20 |
WO2007128588A3 (de) | 2008-06-05 |
US20090169537A1 (en) | 2009-07-02 |
US8465736B2 (en) | 2013-06-18 |
WO2007128588A2 (de) | 2007-11-15 |
EP2015743B1 (de) | 2016-08-17 |
EP2015743A2 (de) | 2009-01-21 |
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