JP2005520561A - Prdm11の変更された発現に関連する癌における新規組成物および方法 - Google Patents
Prdm11の変更された発現に関連する癌における新規組成物および方法 Download PDFInfo
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Abstract
Description
本出願は、米国特許出願第10/034,650号(2001年11月20日出願)同第09/747,377号(2000年12月22日出願)、および同第09/798,586号(2001年3月2日出願)という出願の継続出願であり、これら全ての出願は、本明細書中に参考として特に援用される。
本発明は、癌(特に乳癌を含む癌腫)の診断および処置における使用のための新規配列、ならびにスクリーニング方法における新規組成物の使用に関する。
癌遺伝子は、癌を生じさせ得る遺伝子である。発癌は、広範な種々の機構(細胞の、癌遺伝子を含むウイルスによる感染、宿主ゲノムにおける癌原遺伝子の活性化、および癌原遺伝子および腫瘍抑制遺伝子の変異を含む)によって、起こり得る。
上で概略を述べた目的に従い、本発明は、癌腫(特に乳癌)を調節する組成物のスクリーニングの方法を提供する。本明細書中で、細胞(好ましくは乳癌)の増殖を阻害する方法もまた、提供される。癌腫を処置する方法(診断を含む)もまた、本明細書中で提供される。
本発明は、癌腫(特にリンパ腫、乳癌または前立腺癌)に関連する多くの配列に関連する。クローン的に組み込まれたプロウイルス(clonally−integrated provirus)と癌原遺伝子との間の比較的緊密な連結は、「プロウイルスタギング(provirus tagging)」を形成し、ここで、挿入変異メカニズム(insertion mutation mechanism)により作用する遅性トランスフォーミングレトロウイルスが、癌原遺伝子を単離するために使用される。いくつかのモデルにおいて、非感染動物は、低い癌比率を有し、そして感染動物は、高い癌比率を有する。関係するレトロウイルスの多くは、形質導入された宿主癌原遺伝子または病原性トランス作用性(trans−acting)ウイルス遺伝子を持たないため、癌発生率は、宿主癌原遺伝子に影響を及ぼすプロウイルスの組み込みの直接的な結果であることは、公知である。プロウイルスの組み込みはランダムであるため、極少数の組み込み体(integrant)が、選択的増殖有利性を提供する宿主癌原細胞を「活性化」する。この稀な出来事は、腫瘍のクローン化学量論において新しいプロウイルスを生じる。
CA配列は、CA配列(本明細書中で概略を示される)に対する実質的な核酸および/またはアミノ酸の配列相同性により、最初に同定される。このような相同性は、核酸またはアミノ酸の配列全体に基づき得、大概、相同性プログラムまたはハイブリダイゼーション条件のどちらかを使用して、以下で概略を示したように、決定される。
mRNAを、当該分野において公知の標準的手順によって乳癌サンプルから調製した。遺伝子発現を5’ヌクレアーゼ(TaqMan)化学を用いるABI 7900HTSequence Detection Systemによる定量的PCRによって測定した。この化学は、2つのPCRプライマー間をアニールする二重標識(レポーターおよびクエンチャー)蛍光プローブの付加による標準的PCRとは異なる。レポーター染料の蛍光は、隣接しているクエンチャーによってクエンチされる。サーマルサイクルの間、Taq DNAポリメラーゼの5’ヌクレアーゼ活性は、アニールされたプローブを切断し、レポーターおよびクエンチャー染料を遊離させる。蛍光の増強が認められ、蛍光がバックグラウンドを超えて増強するサイクル回数は、対数線形様式において開始テンプレート濃度に関連する。
Claims (19)
- 表1に概説された配列からなる群から選択されたヌクレオチド配列を含む、組換え核酸。
- 請求項1に記載の組換え核酸を含む、宿主細胞。
- 請求項2に記載の組換え核酸を含む、発現ベクター。
- 請求項3に記載の発現ベクターを含む、宿主細胞。
- 表1に概説された配列からなる群から選択された配列を含む、核酸配列によりコードされたアミノ酸配列を含む、組換えタンパク質。
- 薬剤候補をスクリーニングする方法であって、該方法は、以下:
a)表1に概説された配列またはそのフラグメントからなる群より選択された核酸配列を含む、癌関連性(CA)遺伝子を発現する細胞を提供する工程;
b)薬剤候補を該細胞に添加する工程;および
c)該CA遺伝子の発現における該薬剤候補の効果を決定する工程、
を包含する、方法。 - 前記決定する工程は、前記薬剤候補の非存在下における発現レベルと、該薬剤候補の存在下における発現レベルの比較を包含する、請求項6に記載の方法。
- CAタンパク質(CAP)に結合し得る生物活性因子をスクリーニングする方法であって、該CAPは、表1に概説された配列からなる群より選択された核酸配列を含む核酸によりコードされ、該方法は、以下:
a)該CAPおよび候補生物活性因子を合わせる工程;および
b)該候補因子と該CAPとの結合を決定する工程、
を包含する、方法。 - CAタンパク質(CAP)の活性を調節し得る生物活性因子をスクリーニングする方法であって、該CAPは、表1に概説された配列からなる群から選択された核酸配列を含む核酸によりコードされ、該方法は、以下:
a)該CAPおよび候補生物活性因子を合わせる工程;および
b)該CAPの該生物活性における該候補因子の効果を決定する工程、
を包含する、方法。 - 候補癌薬剤の効果を評価する方法であって、該方法は、以下:
a)患者に該薬剤を投与する工程;
b)該患者から細胞サンプルを取り出す工程;および
c)表1に概説された前記配列からなる群より選択された核酸配列を含む、遺伝子の発現または活性の変化を決定する工程、
を包含する、方法。 - 癌腫を診断する方法であって、該方法は、以下:
a)第1の個体の第1の組織型における、表1に概説された配列からなる群より選択された核酸配列を含む、一つ以上の遺伝子の発現を決定する工程;および
b)該遺伝子の発現と該第1の個体に由来する第2の正常な組織型または第2の罹患していない個体に由来する正常な組織型とを比較する工程;
を包含し、
該発現の相違は、該第1の個体は癌腫を有することを表す、方法。 - CAタンパク質(CAP)の活性を阻害する方法であって、該CAPは、表1に概説された前記配列からなる群より選択された核酸配列を含む核酸によりコードされ、阻害因子と該CAPとを結合させる工程を包含する、方法。
- CAタンパク質(CAP)の阻害因子を患者に投与することを包含する、癌腫を処置する方法であって、該CAPは、表1に概説された配列からなる群から選択された核酸配列を含む核酸によってコードされる、方法。
- CAタンパク質(CAP)の効果を中和する方法であって、該CAPは、表1に概説された配列からなる群から選択された核酸配列を含む核酸によりコードされ、中和をもたらすのに十分な量で該CAPタンパク質と該CAPタンパク質に特異的な因子とを接触させる工程を包含する、方法。
- 表1に概説された配列からなる群から選択された核酸配列を含む核酸によりコードされたタンパク質と特異的に結合するポリペプチド。
- 表1に概説された配列からなる群より選択された核酸配列を含む核酸によりコードされたタンパク質と特異的に結合する抗体を含む、請求項15に記載のポリペプチド。
- 表1に概説された配列またはそれらのフラグメントの核酸からなる群より選択された、一つ以上の核酸セグメントを含む、バイオチップ。
- 個体の少なくとも一つのCA遺伝子を配列決定することにより、癌腫または癌腫の性質を診断する方法。
- ハイブリダイゼーションに適した条件下で、個体に由来するゲノムDNAサンプルにCA遺伝子プローブを添加する工程を包含する、CA遺伝子コピー数を決定する方法。
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
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US10/105,637 US20030087252A1 (en) | 2000-12-22 | 2002-03-20 | Novel compositions and methods in cancer associated with altered expression of PRDM11 |
PCT/US2003/008808 WO2003081251A1 (en) | 2002-03-20 | 2003-03-20 | Novel compositions and methods in cancer associated with altered expression of prdm 11 |
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JP2009107166A Division JP2009195242A (ja) | 2002-03-20 | 2009-04-24 | Prdm11の変更された発現に関連する癌における新規組成物および方法 |
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JP2005520561A true JP2005520561A (ja) | 2005-07-14 |
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JP2009107166A Withdrawn JP2009195242A (ja) | 2002-03-20 | 2009-04-24 | Prdm11の変更された発現に関連する癌における新規組成物および方法 |
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US20090215711A1 (en) * | 2004-04-30 | 2009-08-27 | Sagres Discovery, Inc. | Novel compositions and methods in cancer |
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US564802A (en) * | 1896-07-28 | shepard | ||
US4179337A (en) * | 1973-07-20 | 1979-12-18 | Davis Frank F | Non-immunogenic polypeptides |
JPS6023084B2 (ja) * | 1979-07-11 | 1985-06-05 | 味の素株式会社 | 代用血液 |
US4469863A (en) * | 1980-11-12 | 1984-09-04 | Ts O Paul O P | Nonionic nucleic acid alkyl and aryl phosphonates and processes for manufacture and use thereof |
US4640835A (en) * | 1981-10-30 | 1987-02-03 | Nippon Chemiphar Company, Ltd. | Plasminogen activator derivatives |
US4816567A (en) * | 1983-04-08 | 1989-03-28 | Genentech, Inc. | Recombinant immunoglobin preparations |
US4496689A (en) * | 1983-12-27 | 1985-01-29 | Miles Laboratories, Inc. | Covalently attached complex of alpha-1-proteinase inhibitor with a water soluble polymer |
US5430136A (en) * | 1984-10-16 | 1995-07-04 | Chiron Corporation | Oligonucleotides having selectably cleavable and/or abasic sites |
US5235033A (en) * | 1985-03-15 | 1993-08-10 | Anti-Gene Development Group | Alpha-morpholino ribonucleoside derivatives and polymers thereof |
US5034506A (en) * | 1985-03-15 | 1991-07-23 | Anti-Gene Development Group | Uncharged morpholino-based polymers having achiral intersubunit linkages |
EP0206448B1 (en) * | 1985-06-19 | 1990-11-14 | Ajinomoto Co., Inc. | Hemoglobin combined with a poly(alkylene oxide) |
US4791192A (en) * | 1986-06-26 | 1988-12-13 | Takeda Chemical Industries, Ltd. | Chemically modified protein with polyethyleneglycol |
US5124246A (en) * | 1987-10-15 | 1992-06-23 | Chiron Corporation | Nucleic acid multimers and amplified nucleic acid hybridization assays using same |
US5359100A (en) * | 1987-10-15 | 1994-10-25 | Chiron Corporation | Bifunctional blocked phosphoramidites useful in making nucleic acid mutimers |
US5700637A (en) * | 1988-05-03 | 1997-12-23 | Isis Innovation Limited | Apparatus and method for analyzing polynucleotide sequences and method of generating oligonucleotide arrays |
US5216141A (en) * | 1988-06-06 | 1993-06-01 | Benner Steven A | Oligonucleotide analogs containing sulfur linkages |
GB8823869D0 (en) * | 1988-10-12 | 1988-11-16 | Medical Res Council | Production of antibodies |
US5143854A (en) * | 1989-06-07 | 1992-09-01 | Affymax Technologies N.V. | Large scale photolithographic solid phase synthesis of polypeptides and receptor binding screening thereof |
US5386023A (en) * | 1990-07-27 | 1995-01-31 | Isis Pharmaceuticals | Backbone modified oligonucleotide analogs and preparation thereof through reductive coupling |
US5602240A (en) * | 1990-07-27 | 1997-02-11 | Ciba Geigy Ag. | Backbone modified oligonucleotide analogs |
US5661016A (en) * | 1990-08-29 | 1997-08-26 | Genpharm International Inc. | Transgenic non-human animals capable of producing heterologous antibodies of various isotypes |
US5625126A (en) * | 1990-08-29 | 1997-04-29 | Genpharm International, Inc. | Transgenic non-human animals for producing heterologous antibodies |
US5545806A (en) * | 1990-08-29 | 1996-08-13 | Genpharm International, Inc. | Ransgenic non-human animals for producing heterologous antibodies |
US5633425A (en) * | 1990-08-29 | 1997-05-27 | Genpharm International, Inc. | Transgenic non-human animals capable of producing heterologous antibodies |
DK0546073T3 (da) * | 1990-08-29 | 1998-02-02 | Genpharm Int | Frembringelse og anvendelse af transgene, ikke-humane dyr, der er i stand til at danne heterologe antistoffer |
US5644048A (en) * | 1992-01-10 | 1997-07-01 | Isis Pharmaceuticals, Inc. | Process for preparing phosphorothioate oligonucleotides |
US5681697A (en) * | 1993-12-08 | 1997-10-28 | Chiron Corporation | Solution phase nucleic acid sandwich assays having reduced background noise and kits therefor |
US5637684A (en) * | 1994-02-23 | 1997-06-10 | Isis Pharmaceuticals, Inc. | Phosphoramidate and phosphorothioamidate oligomeric compounds |
US5580731A (en) * | 1994-08-25 | 1996-12-03 | Chiron Corporation | N-4 modified pyrimidine deoxynucleotides and oligonucleotide probes synthesized therewith |
US5597909A (en) * | 1994-08-25 | 1997-01-28 | Chiron Corporation | Polynucleotide reagents containing modified deoxyribose moieties, and associated methods of synthesis and use |
US5681702A (en) * | 1994-08-30 | 1997-10-28 | Chiron Corporation | Reduction of nonspecific hybridization by using novel base-pairing schemes |
US6153441A (en) * | 1998-02-17 | 2000-11-28 | Smithkline Beecham Corporation | Methods of screening for agonists and antagonists for human CCR7 receptor and CKβ-9 ligand and interaction thereof |
US7820447B2 (en) * | 2000-12-22 | 2010-10-26 | Sagres Discovery Inc. | Compositions and methods for cancer |
US20030216558A1 (en) * | 2000-12-22 | 2003-11-20 | Morris David W. | Novel compositions and methods for cancer |
WO2003008583A2 (en) * | 2001-03-02 | 2003-01-30 | Sagres Discovery | Novel compositions and methods for cancer |
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JP2009195242A (ja) | 2009-09-03 |
CA2479723A1 (en) | 2003-10-02 |
AU2003218331A1 (en) | 2003-10-08 |
US20030087252A1 (en) | 2003-05-08 |
WO2003081251A1 (en) | 2003-10-02 |
EP1490688A1 (en) | 2004-12-29 |
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