JP5861242B2 - クラステリンのペプチドリガンド及びその使用 - Google Patents
クラステリンのペプチドリガンド及びその使用 Download PDFInfo
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- JP5861242B2 JP5861242B2 JP2012505008A JP2012505008A JP5861242B2 JP 5861242 B2 JP5861242 B2 JP 5861242B2 JP 2012505008 A JP2012505008 A JP 2012505008A JP 2012505008 A JP2012505008 A JP 2012505008A JP 5861242 B2 JP5861242 B2 JP 5861242B2
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- C07K7/04—Linear peptides containing only normal peptide links
- C07K7/08—Linear peptides containing only normal peptide links having 12 to 20 amino acids
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- 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
- A61K47/50—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/62—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being a protein, peptide or polyamino acid
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Description
a)配列HPLSKHPYWSQP(配列番号1)、
b)配列NTYWSQLLHFQT(配列番号2)、及び
c)配列SHALPLTWSTAA(配列番号3)、
又はそれと実質的に同一の配列を含むペプチドを対象とする。
a)本明細書ではP3378と呼ばれる配列HPLSKHPYWSQP(配列番号1)、
b)本明細書ではP3375と呼ばれる配列NTYWSQLLHFQT(配列番号2)、及び
c)本明細書ではP3376と呼ばれる配列SHALPLTWSTAA(配列番号3)、
を含むペプチドを対象とする。
本明細書に記載の光学イメージング;
11C、13N、15O、18F、64Cu、62Cu、124I、76Br、82Rb及び68Gaなどの一般的な同位体(臨床的には18Fが最も利用される)でペプチドを標識化する陽電子放出断層撮影(PET);
特異的な適用に依存して99mTc、111In、123I、201Tlなどの放射性トレーサーを使用する単一光子放射型コンピュータ断層撮影法(SPECT)(限定するものではないが、例えば133Xeガスは、肺機能評価のための吸入の診断研究に有用であることが示されている);
ペプチドを、例えばそれに限定されるものではないが炭素で被覆した鉄−コバルトナノ粒子と結合させ、それにより腫瘍検出のためのMRIの感受性を増大する磁気共鳴画像(MRI)(この種類のナノ粒子は、近赤外光を吸収し発熱することもでき、これにより腫瘍のイメージングが可能になるだけでなく、腫瘍細胞を熱で死滅させることもできる。最適な注入用量及び投与方法(静脈内(i.v.)又は腹腔内(i.p))は、一般に実験によって決定される)
を含むいくつかの分子イメージング技術において使用することができる。
a.マウスに、アレクサ680で標識化したP3378ペプチド5ナノモル又はアレクサ680で標識化したP3378Rペプチド5ナノモルのいずれかを、尾静脈を介して静脈内(i.v.)注入した。
b.マウスに、アレクサ680で標識化したP3378ペプチド25ナノモル又はアレクサ680で標識化したP3378Rペプチド25ナノモルのいずれかを、尾静脈を介して静脈内(i.v.)注入した。
c.マウスに、ディライト680で標識化したP3378ペプチド25ナノモル及びディライト800色素で標識化したP3378Rペプチド25ナノモルの混合物を、i.v.(尾静脈)同時注入した。
本願は、その内容全体が参照によって本明細書に組み込まれている2009年4月17日出願の米国特許仮出願第61/202,910号の利益を主張するものである。
本明細書に記載のすべての特許、特許出願及び出版物は、参照によって本明細書に組み込まれている。
Berx G, Raspe E, Christofori G, ThieryJP, Sleeman JP. (2007) Pre-EMTing metastasis? Recapitulation of morphogeneticprocesses in cancer. Clin. Exp. Metastasis. 24: 587.
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Gasteiger E. et al. (2005) Proteinidentification and analysis tools on the ExPASy Server. In: John M. Walker(ed): The Proteomics Protocols Handbook, Humana Press; 571-607.
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Lau SH, Sham JS, Xie D, Tzang CH, TangD, Ma N, Hu L, Wang Y, Wen JM, Xiao G, Zhang WM, Lau GK, Yang M, Guan XY.(2006) Clusterin plays an important role in hepatocellular carcinomametastasis. Oncogene. 25: 1242.
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Mourra N, Couvelard A, Tiret E, OlschwangS, Flejou JF. (2007) Clusterin is highly expressed inpancreatic endocrine tumours but not in solid pseudopapillary tumours. Histopathology.50: 331.
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Claims (13)
- 配列番号1で示したアミノ酸配列からなるペプチド。
- 配列番号1又は配列番号2で示したアミノ酸配列からなるペプチド。
- カーゴ分子に連結している、請求項1又は2に記載のペプチド。
- カーゴ分子が、酵素、イメージング部分、放射性同位体又は細胞傷害性薬剤を含む、請求項3に記載のペプチド。
- カーゴ分子がイメージング部分を含む、請求項3に記載のペプチド。
- イメージング部分が、放射標識、フルオロフォア、近赤外蛍光色素又は磁気ナノ粒子を含む、請求項5に記載のペプチド。
- 請求項1から6のいずれか一項に記載のペプチドを含む、分子イメージング剤、又はクラステリンが上方制御されている病状の検出又は診断剤。
- 腫瘍の分子イメージングのための、請求項7に記載の分子イメージング剤。
- 分子イメージングが、光学イメージング、陽電子放出断層撮影、単一光子放射型コンピュータ断層撮影法、又は磁気共鳴画像である、請求項8に記載の分子イメージング剤。
- 病状が癌である、請求項7に記載の検出又は診断剤。
- カーゴ分子に連結したペプチドを含む腫瘍細胞の検出剤であって、前記ペプチドは請求項1又は2に記載のペプチドである、検出剤。
- 前記カーゴ分子がイメージング部分を有する、請求項11に記載の検出剤。
- カーゴ分子に連結したペプチドを含む腫瘍細胞の上皮間葉移行の検出剤であって、前記ペプチドは請求項1又は2に記載のペプチドである、検出剤。
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US20291009P | 2009-04-17 | 2009-04-17 | |
US61/202,910 | 2009-04-17 | ||
PCT/CA2010/000566 WO2010118521A1 (en) | 2009-04-17 | 2010-04-15 | Peptide ligands for clusterin and uses thereof |
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