序号 专利名 申请号 申请日 公开(公告)号 公开(公告)日 发明人
1 改善心脏功能的基于细胞和基因的方法 CN201280034527.5 2012-05-29 CN103946230B 2017-02-08 M·雷尼尔; M·拉弗拉梅; C·默里; F·S·科尔特; S·伦迪; S·D·豪施卡; J·S·张伯伦; G·奥多姆
提供了用于改善哺乳动物的心脏功能、心肌收缩和舒张的组合物和方法。将用一个或多个表达载体转染的心肌细胞移植至哺乳动物心肌,所述表达载体包含有效地连接于启动子的核糖核苷酸还原酶亚基R1编码核酸序列和核糖核苷酸还原酶亚基R2编码核酸序列。还提供了用于通过移植过表达R1和R2的供体细胞而向心肌递送dATP的组合物和方法。由此原位产生dATP并通过在供体细胞和宿主心肌细胞之间形成的缝隙连接而递送。或者,将具有R1和R2编码构建体的病毒载体直接给哺乳动物施用。心脏功能的改善还可通过施用包含编码L48Q-Q、61Q或L57Q cTnC变体的核酸序列的载体来实现。
2 改善心脏功能的基于细胞和基因的方法 CN201280034527.5 2012-05-29 CN103946230A 2014-07-23 M·雷尼尔; M·拉弗拉梅; C·默里; F·S·科尔特; S·伦迪; S·D·豪施卡; J·S·张伯伦
发明提供了用于改善哺乳动物的心脏功能、心肌收缩和舒张的组合物和方法。将用一个或多个表达载体转染的心肌细胞移植至哺乳动物心肌,所述表达载体包含有效地连接于启动子的核糖核苷酸还原酶亚基R1编码核酸序列和核糖核苷酸还原酶亚基R2编码核酸序列。还提供了用于通过移植过表达R1和R2的供体细胞而向心肌递送dATP的组合物和方法。由此原位产生dATP并通过在供体细胞和宿主心肌细胞之间形成的缝隙连接而递送。或者,将具有R1和R2编码构建体的病毒载体直接给哺乳动物施用。心脏功能的改善还可通过施用包含编码L48Q-Q、61Q或L57Q cTnC变体的核酸序列的载体来实现。
3 CELL AND GENE BASED METHODS TO IMPROVE CARDIAC FUNCTION US14122226 2012-05-29 US20160186139A1 2016-06-30 Michael Regnier; Michael Laflamme; Charles Murry; F. Steven Korte; Scott Lundy; Stephen Denison Hauschka; Jeffrey S. Chamberlain
Compositions and methods for improving cardiac function, myocardial contractility and relaxation in a mammal are provided. Cardiomyocytes transfected with one or more expression vectors comprising a ribonucleotide reductase subunit R1-encoding nucleic acid sequence and a ribonucleotide reductase subunit R2-encoding nucleic acid sequence operably linked to a promoter are grafted to a mammalian myocardium. Also provided are compositions and methods for delivering dATP to a myocardium through grafting of donor cells overexpressing R1 and R2. dATP is thereby produced in situ and delivered through gap junctions established between donor cells and host cardiomyocytes. Alternatively, viral vector(s) having the R1 and R2-encoding construct(s) are administered to the mammal directly. Improvement of cardiac function can also be effected by administration of vectors comprising a nucleic acid sequence encoding a L48Q, 61 Q, or L57Q cTnC variant.
4 nrdG US09040213 1998-03-17 US06287804B1 2001-09-11 Michael Terence Black
The invention provides nrdG polypeptides and polynucleotides encoding nrdG polypeptides and methods for producing such polypeptides by recombinant techniques. Also provided are methods for utilizing nrdG polypeptides to screen for antibacterial compounds.
5 Cell and gene based methods to improve cardiac function US14122226 2012-05-29 US09868937B2 2018-01-16 Michael Regnier; Michael Laflamme; Charles Murry; F. Steven Korte; Scott Lundy; Stephen Denison Hauschka; Jeffrey S. Chamberlain; Guy Odom
Compositions and methods for improving cardiac function, myocardial contractility and relaxation in a mammal are provided. Cardiomyocytes transfected with one or more expression vectors comprising a ribonucleotide reductase subunit R1-encoding nucleic acid sequence and a ribonucleotide reductase subunit R2-encoding nucleic acid sequence operably linked to a promoter are grafted to a mammalian myocardium. Also provided are compositions and methods for delivering dATP to a myocardium through grafting of donor cells overexpressing R1 and R2. dATP is thereby produced in situ and delivered through gap junctions established between donor cells and host cardiomyocytes. Alternatively, viral vector(s) having the R1 and R2-encoding construct(s) are administered to the mammal directly. Improvement of cardiac function can also be effected by administration of vectors comprising a nucleic acid sequence encoding a L48Q, 61 Q, or L57Q cTnC variant.
6 nrdG US09884519 2001-06-19 US20020098544A1 2002-07-25 Michael Terence Black
The invention provides nrdG polypeptides and polynucleotides encoding nrdG polypeptides and methods for producing such polypeptides by recombinant techniques. Also provided are methods for utilizing nrdG polypeptides to screen for antibacterial compounds.
7 CELL AND GENE BASED METHODS TO IMPROVE CARDIAC FUNCTION EP12790042 2012-05-29 EP2714709A4 2015-05-13 REGNIER MICHAEL; LAFLAMME MICHAEL; MURRY CHARLES; KORTE F STEVEN; LUNDY SCOTT; HAUSCHKA STEPHEN DENISON; CHAMBERLAIN JEFFREY S
Compositions and methods for improving cardiac function, myocardial contractility and relaxation in a mammal are provided. Cardiomyocytes transfected with one or more expression vectors comprising a ribonucleotide reductase subunit R1-encoding nucleic acid sequence and a ribonucleotide reductase subunit R2-encoding nucleic acid sequence operably linked to a promoter are grafted to a mammalian myocardium. Also provided are compositions and methods for delivering dATP to a myocardium through grafting of donor cells overexpressing R1 and R2. dATP is thereby produced in situ and delivered through gap junctions established between donor cells and host cardiomyocytes. Alternatively, viral vector(s) having the R1 and R2-encoding construct(s) are administered to the mammal directly. Improvement of cardiac function can also be effected by administration of vectors comprising a nucleic acid sequence encoding a L48Q, 61 Q, or L57Q cTnC variant.
8 Cardiac function improvement methods based on cell and gene JP2014512189 2012-05-29 JP2014517694A 2014-07-24 レグニアー、マイケル; ラフラム、マイケル; マリー、チャールズ; コート、エフ.、スティーヴン; ランディー、スコット; ハウシュカ、ステファン、デニソン; チャンバーレイン、ジェフリー、エス.
哺乳動物における心臓機能、心筋収縮性及び弛緩を改善するための組成物及び方法を提供する。 プロモーターと操作可能に連結された、リボヌクレオチドレダクターゼサブユニットR1をコードする核酸配列及びリボヌクレオチドレダクターゼサブユニットR2をコードする核酸配列を含む1以上の発現ベクターでトランスフェクトされた心筋細胞を、哺乳動物心筋に移植する。 あるいは、R1及びR2をコードする構築物(1以上)を有するウイルウスベクター(1以上)を哺乳動物に直接投与する。 R1及びR2サブユニットの過剰発現は、RR複合体の形成をもたらし、続いて、dATPが産生される。 心臓機能の改善は、L48Q置換、I61Q置換又はL57Q置換されたcTnC変異体をコードする核酸配列を含むベクターの投与によっても達成され得る。 また、R1及びR2を過剰発現するドナー細胞の移植を介した、心筋にdATPをデリバリーするための組成物及び方法も提供する。 それにより、dATPはin situで産生され、ドナー細胞と宿主心筋細胞との間に確立されたギャップジャンクションを介してデリバリーされる。
【選択図】図1
9 NrdD JP2000554407 1999-06-09 JP2002517993A 2002-06-25 エドウィナ・アイ・ワイルディング; クリストファー・エム・トレイニ; マイケル・ティ・ブラック
(57)【要約】 本発明はnrdDポリペプチドおよびnrdDポリペプチドをコードするポリヌクレオチドならびに組換え技法によりかかるポリペプチドを産生する方法を提供する。 さらに、nrdDポリペプチドを用いて抗菌性化合物をスクリーニングする方法も提供する。
10 細胞及び遺伝子に基づく心臓機能改善方法 JP2014512189 2012-05-29 JP6162104B2 2017-07-12 レグニアー、マイケル; ラフラム、マイケル; マリー、チャールズ; コート、エフ.、スティーヴン; ランディー、スコット; ハウシュカ、ステファン、デニソン; チャンバーレイン、ジェフリー、エス.; オドム、ガイ
11 nrdG JP2000536387 1999-03-15 JP2002506826A 2002-03-05 マイケル・ティ・ブラック
(57)【要約】 本発明はnrdGポリペプチドおよびnrdGポリペプチドをコードするポリヌクレオチド、ならびに組換え法によるかかるポリペプチドの製造方法を提供する。 また、抗菌化合物をスクリーニングするためにnrdGポリペプチドを利用する方法を提供する。
12 COMPOSITIONS FOR USE IN CELL AND GENE BASED METHODS TO IMPROVE CARDIAC FUNCTION EP12790042.1 2012-05-29 EP2714709B1 2018-04-18 REGNIER, Michael; LAFLAMME, Michael; MURRY, Charles; KORTE, F., Steven; LUNDY, Scott; HAUSCHKA, Stephen, Denison; CHAMBERLAIN, Jeffrey, S.; ODOM, Guy
Compositions and methods for improving cardiac function, myocardial contractility and relaxation in a mammal are provided. Cardiomyocytes transfected with one or more expression vectors comprising a ribonucleotide reductase subunit R1-encoding nucleic acid sequence and a ribonucleotide reductase subunit R2-encoding nucleic acid sequence operably linked to a promoter are grafted to a mammalian myocardium. Also provided are compositions and methods for delivering dATP to a myocardium through grafting of donor cells overexpressing R1 and R2. dATP is thereby produced in situ and delivered through gap junctions established between donor cells and host cardiomyocytes. Alternatively, viral vector(s) having the R1 and R2-encoding construct(s) are administered to the mammal directly. Improvement of cardiac function can also be effected by administration of vectors comprising a nucleic acid sequence encoding a L48Q, 61 Q, or L57Q cTnC variant.
13 CELL AND GENE BASED METHODS TO IMPROVE CARDIAC FUNCTION EP12790042.1 2012-05-29 EP2714709A2 2014-04-09 REGNIER, Michael; LAFLAMME, Michael; MURRY, Charles; KORTE, F., Steven; LUNDY, Scott; HAUSCHKA, Stephen, Denison; CHAMBERLAIN, Jeffrey, S.
Compositions and methods for improving cardiac function, myocardial contractility and relaxation in a mammal are provided. Cardiomyocytes transfected with one or more expression vectors comprising a ribonucleotide reductase subunit R1-encoding nucleic acid sequence and a ribonucleotide reductase subunit R2-encoding nucleic acid sequence operably linked to a promoter are grafted to a mammalian myocardium. Also provided are compositions and methods for delivering dATP to a myocardium through grafting of donor cells overexpressing R1 and R2. dATP is thereby produced in situ and delivered through gap junctions established between donor cells and host cardiomyocytes. Alternatively, viral vector(s) having the R1 and R2-encoding construct(s) are administered to the mammal directly. Improvement of cardiac function can also be effected by administration of vectors comprising a nucleic acid sequence encoding a L48Q, 61 Q, or L57Q cTnC variant.
14 NrdD EP99957023.7 1999-06-09 EP1087792A1 2001-04-04 WILDING, Edwina, I.; BLACK, Michael, T.; TRAINI, Christopher, M.
The invention provides nrdD polypeptides and polynucleotides encoding nrdD polypeptides and methods for producing such polypeptides by recombinant techniques. Also provided are methods for utilizing nrdD polypeptides to screen for antibacterial compounds.
15 nrdG EP99912551.1 1999-03-15 EP1064007A1 2001-01-03 BLACK, Michael, T.
The invention provides nrdG polypeptides and polynucleotides encoding nrdG polypeptides and methods for producing such polypeptides by recombinant techniques. Also provided are methods for utilizing nrdG polypeptides to screen for antibacterial compounds.
16 세포 및 유전자에 기반한 심장 기능을 개선하는 방법 KR1020137034630 2012-05-29 KR1020140035967A 2014-03-24 레그니어미셸; 라플레임미셸; 머리찰스; 코르테에프.스티븐; 룬디스코트; 호쉬카스테펜데니슨; 챔버레인제프리에스.; 오돔,가이
[0464] 포유 동물 중에서의 심장 기능, 심근 수축 및 이완을 개선하는 조성물 및 방법이 제공된다. 프로모터에 작동가능하게 연결된 리보뉴클레오타이드 리덕타제 서브 유닛 R1-인코딩 핵산 서열 및 리보뉴클레오타이드 리덕타제 서브 유닛 R2-인코딩 핵산 서열을 포함하는 1 이상의 발현 벡터로 감염시킨 심근 세포를 포유 동물의 심근에 이식한다. 또는 R1 및 R2-인코딩 컨스트럭트를 가지는 바이러스 벡터를 포유 동물에 직접적으로 투여한다. R1 및 R2 서브 유닛의 과발현은 RR 복합체의 형성과 그에 따른 dATP 생성을 일으킨다. 또한, L48Q-치환된, I61Q-치환된, 또는 L57Q-치환된 cTnC 변이체를 인코딩하는 핵산 서열을 포함하는 벡터를 투여하는 것에 의하여, 심장 기능의 개선이 수행될 수 있다. 또한, R1 및 R2를 과발현하는 기증자 세포를 이식하는 것을 통하여 심근에 dATP를 전달하는 조성물 및 방법이 제공된다. 그에 따라 dATP가 인 시투 생산되고, 기증자 세포 및 숙주 심근 세포간에 형성된 갭 결합을 통하여 전달된다.
17 CELL AND GENE BASED METHODS TO IMPROVE CARDIAC FUNCTION PCT/US2012039897 2012-05-29 WO2012162705A3 2013-02-28 REGNIER MICHAEL; LAFLAMME MICHAEL; MURRY CHARLES; KORTE F STEVEN; LUNDY SCOTT; HAUSCHKA STEPHEN DENISON; CHAMBERLAIN JEFFREY S
Compositions and methods for improving cardiac function, myocardial contractility and relaxation in a mammal are provided. Cardiomyocytes transfected with one or more expression vectors comprising a ribonucleotide reductase subunit Rl-encoding nucleic acid sequence and a ribonucleotide reductase subunit R2-encoding nucleic acid sequence operably linked to a promoter are grafted to a mammalian myocardium. Also provided are compositions and methods for delivering dATP to a myocardium through grafting of donor cells overexpressing R1 and R2. dATP is thereby produced in situ and delivered through gap junctions established between donor cells and host cardiomyocytes. Alternatively, viral vector(s) having the Rl and R2-encoding construct(s) are administered to the mammal directly. Improvement of cardiac function can also be effected by administration of vectors comprising a nucleic acid sequence encoding a L48Q, 61 Q, or L57Q cTnC variant.
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