JP2014516993A - 長時間作用型glp−1/グルカゴン受容体アゴニスト - Google Patents
長時間作用型glp−1/グルカゴン受容体アゴニスト Download PDFInfo
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Abstract
【選択図】図13
Description
本願は、2011年6月2日出願の米国特許仮出願第61/492,448号および2012年4月16日出願の米国特許仮出願第61/624,589号の優先権を主張する。これらの出願は、参照により本明細書中で援用される。
Claims (39)
- 組成物であって、
オキシントモジュリンと、
ポリエチレングリコールポリマー(PEGポリマー)と、
9−フルオレニルメトキシカルボニル(Fmoc)または2−スルホ−9−フルオレニルメトキシカルボニル(FMS)とを含んでなる組成物。 - 前記PEGポリマーが、前記オキシントモジュリンのアミノ末端またはリシン残基に、FmocまたはFMSを介して結合されることを特徴とする請求項1に記載の組成物。
- 前記オキシントモジュリンが、配列番号1で記述されるアミノ酸配列からなることを特徴とする請求項1に記載の組成物。
- 前記PEGポリマーが、スルフヒドリル部分を有するPEGポリマーであることを特徴とする請求項1に記載の組成物。
- 前記PEGポリマーが、PEG30、PEG40またはPEG60であることを特徴とする請求項1に記載の組成物。
- 請求項1に記載の組成物および薬学的に許容可能な担体を含む薬学的組成物。
- オキシントモジュリンの生物学的半減期を延長するための方法であって、
オキシントモジュリンと、ポリエチレングリコールポリマー(PEGポリマー)と、9−フルオレニルメトキシカルボニル(Fmoc)または2−スルホ−9−フルオレニルメトキシカルボニル(FMS)とを、約1:1:0.5〜約1:1:3.5のモル比で結合させるステップを含む方法。 - 前期オキシントモジュリンが、配列番号1のアミノ酸配列からなることを特徴とする請求項7に記載の方法。
- 前記PEGポリマーが、前記オキシントモジュリンのアミノ末端またはリシン残基に、FmocまたはFMSを介して結合されることを特徴とする請求項7に記載の方法。
- 前記PEGポリマーが、スルフヒドリル部分を有するPEGポリマーであることを特徴とする請求項7に記載の方法。
- 前記PEGポリマーが、PEG30、PEG40またはPEG60であることを特徴とする請求項7に記載の方法。
- 対象のグルコース耐容性、血糖制御またはその両方を誘導する方法であって、
有効量の請求項1に記載の組成物および薬学的に許容可能な担体を、前記対象に対して投与するステップを含む方法。 - 前記オキシントモジュリンが、配列番号1のアミノ酸配列からなることを特徴とする請求項12に記載の方法。
- 前記PEGポリマーが、前記オキシントモジュリンのアミノ末端またはリシン残基に、FmocまたはFMSを介して結合されることを特徴とする請求項12に記載の方法。
- 前記PEGポリマーが、スルフヒドリル部分を有するPEGポリマーであることを特徴とする請求項12に記載の方法。
- 前記PEGポリマーが、PEG30、PEG40またはPEG60であることを特徴とする請求項12に記載の方法。
- オキシントモジュリンの曲線下面積(AUC)の改善方法であって、
ポリエチレングリコールポリマー(PEGポリマー)を、前記オキシントモジュリンのアミノ末端に、9−フルオレニルメトキシカルボニル(Fmoc)または2−スルホ−9−フルオレニルメトキシカルボニル(FMS)を介して結合させるステップを含む方法。 - 前記オキシントモジュリンが、配列番号1のアミノ酸配列からなることを特徴とする請求項17に記載の方法。
- 前記PEGポリマーが、前記オキシントモジュリンのアミノ末端またはリシン残基に、FmocまたはFMSを介して結合されることを特徴とする請求項17に記載の方法。
- 前記PEGポリマーが、スルフヒドリル部分を有するPEGポリマーであることを特徴とする請求項17に記載の方法。
- 前記PEGポリマーが、PEG30、PEG40またはPEG60であることを特徴とする請求項17に記載の方法。
- オキシントモジュリンの投薬回数を減らすための方法であって、
ポリエチレングリコールポリマー(PEGポリマー)を、前記オキシントモジュリンのアミノ末端に、9−フルオレニルメトキシカルボニル(Fmoc)または2−スルホ−9−フルオレニルメトキシカルボニル(FMS)を介して結合させるステップを含む方法。 - 前記オキシントモジュリンが、配列番号1のアミノ酸配列からなることを特徴とする請求項22に記載の方法。
- 前記PEGポリマーが、前記オキシントモジュリンのアミノ末端またはリシン残基に、FmocまたはFMSを介して結合されることを特徴とする請求項22に記載の方法。
- 前記PEGポリマーが、スルフヒドリル部分を有するPEGポリマーであることを特徴とする請求項22に記載の方法。
- 前記PEGポリマーが、PEG30、PEG40またはPEG60であることを特徴とする請求項22に記載の方法。
- 対象における食物摂取を低減するための、体重を低減するための、またはその両方のための方法であって、
フレキシブルリンカーを介してポリエチレングリコールポリマー(PEGポリマー)に結合されたオキシントモジュリンを、前記対象に対して投与するステップを含み、
前記フレキシブルリンカーが、9−フルオレニルメトキシカルボニル(Fmoc)または2−スルホ−9−フルオレニルメトキシカルボニル(FMS)である方法。 - 前記オキシントモジュリンが、配列番号1のアミノ酸配列からなることを特徴とする請求項27に記載の方法。
- 前記PEGポリマーが、前記オキシントモジュリンのアミノ末端またはリシン残基に、FmocまたはFMSを介して結合されることを特徴とする請求項27に記載の方法。
- 前記PEGポリマーが、スルフヒドリル部分を有するPEGポリマーであることを特徴とする請求項27に記載の方法。
- 前記PEGポリマーが、PEG30、PEG40またはPEG60であることを特徴とする請求項27に記載の方法。
- 対象におけるインスリン感受性を増大させる方法であって、
ポリエチレングリコールポリマー(PEGポリマー)に結合されたオキシントモジュリンを含む有効量の組成物を、前記対象に対して投与するステップを含む方法。 - 前記PEGポリマーが、PEG30、PEG40またはPEG60であることを特徴とする請求項32に記載の方法。
- 前記オキシントモジュリンが、前記ポリエチレングリコールポリマー(PEGポリマー)に、リンカーを介して結合されることを特徴とする請求項32に記載の方法。
- 前記リンカーが、開裂可能なフレキシブルリンカーであることを特徴とする請求項33に記載の方法。
- 前記リンカーが、非開裂可能リンカーであることを特徴とする請求項33に記載の方法。
- 前記フレキシブルリンカーが、9−フルオレニルメトキシカルボニル(Fmoc)または2−スルホ−9−フルオレニルメトキシカルボニル(FMS)であることを特徴とする請求項35に記載の方法。
- 前記リンカーが、N−(ε−マレイミドカプロイルオキシ)スクシンイミドエステル(EMCS)であることを特徴とする請求項36に記載の方法。
- 前記組成物の投与により、前記対象におけるインスリン感受性の急速な増大を生じさせるようにしたことを特徴とする請求項32に記載の方法。
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