JP2001513777A - アルツハイマー病の処置または予防のために効果的な薬物をスクリーニングするためのトランスジェニック動物および細胞株 - Google Patents
アルツハイマー病の処置または予防のために効果的な薬物をスクリーニングするためのトランスジェニック動物および細胞株Info
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Abstract
Description
Claims (1)
- 【特許請求の範囲】 1.配列番号1のDNA分子もしくはこれに少なくとも40%相同であるDNA分子、ま たはそれらのフラグメントを含むDNA構築物であって、ここで、該DNA分子が異種 性の神経特異的プロモーターの制御下にある、DNA構築物。 2.ベクター内に含まれる、請求項1に記載のDNA構築物。 3.ビリオンにより含まれる、請求項1に記載のDNA構築物。 4.前記DNA分子が配列番号1を有する、請求項1に記載のDNA構築物。 5.請求項1に記載のDNA構築物で形質転換された、宿主細胞。 6.ニューロン細胞である、請求項5に記載の宿主細胞株。 7.トランスジェニック非ヒト動物であって、その生殖細胞および体細胞の全て が、配列番号1のDNA分子またはこれに少なくとも40%相同なDNA分子を含む、ト ランスジェニック非ヒト動物。 8.それぞれの生殖細胞および体細胞に含まれる前記DNA分子が配列番号1を有 する、請求項7に記載のトランスジェニック非ヒト動物。 9.前記DNA分子によりコードされるタンパク質が、前記動物の脳において過剰 発現される、請求項7に記載のトランスジェニック非ヒト動物。 10.アルツハイマー病、神経外胚葉腫瘍、悪性星状細胞腫および膠芽腫の処置 または予防のために潜在的に有用である候補薬物をスクリーニングするためのイ ンビトロ方法であって、以下の工程を包含する、方法: (a)候補薬物と請求項5に記載の宿主細胞株とを接触させる工程;および (b)該候補薬物と接触させなかったコントロール細胞株と比較して、該候補 薬物による、以下のうち少なくとも1つを検出する工程: (i)DNA構築物によりコードされるタンパク質発現の抑制もしくは防止; (ii)該DNA構築物によりコードされるタンパク質分解の増加;または (iii)神経突起の出芽、神経細胞死、ニューロンの変性、神経原線維変化 もしくは該宿主における不規則的な腫脹した神経突起および軸索のうち少なくと も1つの頻度の減少。 11.前記タンパク質が配列番号2を有する、請求項10に記載の方法。 12.前記タンパク質が前記宿主細胞により過剰発現される、請求項10に記載 の方法。 13.前記細胞がニューロン細胞である、請求項10に記載の方法。 14.アルツハイマー病、神経外胚葉腫瘍、悪性星状細胞腫および膠芽腫の処置 または予防のための潜在的に有用である候補薬物をスクリーニングするためのイ ンビボ方法であって、以下の工程を包含する、方法: (a)候補薬物を請求項7に記載のトランスジェニック動物に投与する工程、 および (b)該候補薬物を受けなかったコントロール動物と比較して、該候補薬物に よる、以下のうち少なくとも1つを検出する工程: (i)該動物により含まれるDNA構築物によりコードされるタンパク質発現 の抑制もしくは防止; (ii)該動物により含まれる該DNA構築物によりコードされるタンパク質分 解の増加;または (iii)神経突起の出芽、神経細胞死、ニューロンの変性、神経原線維変化 もしくは宿主における不規則的な腫脹した神経突起および軸索のうち少なくとも 1つの頻度の減少。 15.前記動物により含まれる前記DNA構築物が配列番号1を有する、請求項1 4に記載の方法。 16.前記動物により含まれる前記DNA構築物によりコードされる前記タンパク 質が、該動物の脳において過剰発現される、請求項14に記載の方法。 17.配列番号1のヌクレオチド150〜1139に対応するNTP mRNA配列に相補的で ある、アンチセンスオリゴヌクレオチド。 18.15〜40マーである、請求項17に記載のアンチセンスオリゴヌクレオチド 。 19.前記アンチセンスオリゴヌクレオチドが、配列番号9〜11からなる群から 選択される、請求項17に記載のアンチセンスオリゴヌクレオチド。 20.デオキシリボ核酸である、請求項17に記載のアンチセンスオリゴヌクレ オチド。 21.デオキシリボ核酸ホスホロチオエートである、請求項17に記載のアンチ センスオリゴヌクレオチド。 22.デオキシリボ核酸またはデオキシリボ核酸ホスホロチオエートの誘導体で ある、請求項17に記載のアンチセンスオリゴヌクレオチド。 23.請求項17に記載のアンチセンスオリゴヌクレオチドおよび薬学的に受容 可能なキャリアを含む、薬学的組成物。 24.配列番号1のヌクレオチド150〜1139に対応するNTP mRNA配列に対して相 補的である標的配列を含む、リボザイム。 25.請求項24に記載のリボザイムおよび薬学的に受容可能なキャリアを含む 、薬学的組成物。 26.AD7c-NTPコード核酸の一領域と三重鎖領域を形成し、そして配列3'X5'-L- 5'X3'を有するオリゴデオキシヌクレオチドであって、ここでXは配列番号1の ヌクレオチド150〜1139に対応するAD7c-NTP核酸配列を含み、そしてここでLは オリゴヌクレオチドリンカーまたは結合を表す、オリゴデオキシヌクレオチド。 27.請求項26に記載のオリゴデオキシヌクレオチドおよび薬学的に受容可能 なキャリアを含む、薬学的組成物。 28.AD7c-NTPコード核酸の一領域と三重鎖領域を形成し、そして配列5'X3'-L- 3'X5'配列を有するオリゴデオキシヌクレオチドであって、ここでXは配列番号 1のヌクレオチド150〜1139に対応するAD7c-NTP核酸配列を含み、そしてここで Lはオリゴヌクレオチドのリンカーまたは結合を表す、オリゴデオキシヌクレオ チド。 29.請求項28に記載のオリゴデオキシヌクレオチドおよび薬学的に受容可能 なキャリアを含む、薬学的組成物。 30.リボヌクレオチド外部ガイド核酸分子が、3'NCCAヌクレオチド配列に融合 した配列番号1のヌクレオチド150〜1139に対応する10マーのヌクレオチド配列 を含み、ここでNがプリンである、リボヌクレオチド外部ガイド核酸分子。 31.配列番号12〜14のいずれか1つからなる群から選択される、請求項30に 記載のリボヌクレオチド外部ガイド核酸分子。 32.請求項30に記載のリボヌクレオチドおよび薬学的に受容可能なキャリア を含む、薬学的組成物。 33.ニューロンの変性のアルツハイマー型の痴呆を処置または予防するため; または神経外胚葉腫瘍、悪性星状細胞腫もしくは膠芽腫を処置および予防するた めの方法であって、それを必要とする動物に請求項17、24、26、28、ま たは30のいずれか1項に記載のアンチセンスオリゴヌクレオチド、リボザイム 、三重らせん形成オリゴヌクレオチドまたはリボヌクレオチド外部ガイド配列を 投与する工程を包含する、方法。 34.前記アンチセンスオリゴヌクレオチド、リボザイム、三重らせん形成オリ ゴヌクレオチドまたはリボヌクレオチド外部ガイド配列が、前記動物に薬学的に 受容可能なキャリアの一部として投与される、請求項32に記載の方法。
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JP2016529914A (ja) * | 2013-09-13 | 2016-09-29 | エフ.ホフマン−ラ ロシュ アーゲーF. Hoffmann−La Roche Aktiengesellschaft | ポリA−キャリヤーにより誘導される高分子量PCR生成物の生成を避けるためのオリゴ−dT分子の適用 |
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US6271360B1 (en) * | 1999-08-27 | 2001-08-07 | Valigen (Us), Inc. | Single-stranded oligodeoxynucleotide mutational vectors |
CA2446480A1 (en) * | 2001-05-04 | 2002-11-14 | Nymox Corporation | Method of preventing cell death using antibodies to neural thread proteins |
ATE350396T1 (de) * | 2001-05-25 | 2007-01-15 | Nymox Corp | Von neurofilamentproteinen abgeleitete peptide und deren medizinische verwendung |
US6770797B2 (en) * | 2001-06-01 | 2004-08-03 | Rhode Island Hospital | Non-Transgenic nonhuman model for Alzheimer's Disease using a AD7c-NTP nucleic acid |
EP1847550A3 (en) * | 2001-07-19 | 2008-01-09 | Nymox Corporation | Peptides effective in the treatment of tumors and other conditions requiring the removal or destruction of cells |
DE60217507T2 (de) * | 2001-07-19 | 2007-11-15 | Nymox Corp., Saint-Laurent | Peptide für die behandlung von tumoren und anderen zuständen, die das entfernen oder zerstören von zellen erfordern |
DE10154399A1 (de) * | 2001-11-06 | 2003-05-15 | Basf Lynx Bioscience Ag | Verfahren zur Identifizierung von Wirksubstanzen für die Modulation der pip92-vermittelten Apoptose |
EP1714979A3 (en) * | 2001-11-16 | 2007-04-25 | Nymox Corporation | Peptides effective in the treatment of tumors and other conditions requiring the removal or destruction of cells |
US7317077B2 (en) | 2001-11-16 | 2008-01-08 | Nymox Pharmaceutical Corporation | Peptides effective in the treatment of tumors and other conditions requiring the removal or destruction of cells |
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US7544771B2 (en) | 2005-02-23 | 2009-06-09 | Nymox Corporation | Protein and its use in diagnosing Alzheimer's disease |
US7768422B2 (en) * | 2006-09-06 | 2010-08-03 | Carmen Jr Lawrence R | Method of restoring a remote wireless control device to a known state |
WO2009154770A2 (en) | 2008-06-18 | 2009-12-23 | The Texas A & M University System | Mesenchymal stem cells, compositions, and methods for treatment of cardiac tissue damage |
US11628202B2 (en) | 2015-07-24 | 2023-04-18 | Nymox Corporation | Methods of reducing the need for surgery in patients suffering from benign prostatic hyperplasia |
US10183058B2 (en) | 2016-06-17 | 2019-01-22 | Nymox Corporation | Method of preventing or reducing the progression of prostate cancer |
US10172910B2 (en) | 2016-07-28 | 2019-01-08 | Nymox Corporation | Method of preventing or reducing the incidence of acute urinary retention |
US10532081B2 (en) | 2016-09-07 | 2020-01-14 | Nymox Corporation | Method of ameliorating or preventing the worsening or the progression of symptoms of BPH |
US10335453B2 (en) | 2017-03-01 | 2019-07-02 | Nymox Corporation | Compositions and methods for improving sexual function |
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US4873191A (en) * | 1981-06-12 | 1989-10-10 | Ohio University | Genetic transformation of zygotes |
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ES2094733T3 (es) * | 1988-12-21 | 1997-02-01 | Gen Hospital Corp | Deteccion de enfermedades o disfunciones neurologicas. |
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ATE147098T1 (de) | 1990-10-12 | 1997-01-15 | Max Planck Gesellschaft | Abgeänderte ribozyme |
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