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1. 发明授权

US06586203B1 ARF-P19, a novel regulator of the mammalian cell cycle 有权
公开(公告)号：US06586203B1
公开(公告)日：2003-07-01
申请号：US09129855
申请日：1998-08-06
申请人： Charles J. Sherr , Dawn Quelle , Martine F. Roussel , Frederique Zindy
发明人： Charles J. Sherr , Dawn Quelle , Martine F. Roussel , Frederique Zindy
IPC分类号： C12P2106
CPC分类号： C07K14/4703 , A01K2217/05 , A01K2217/075 , A61K38/00 , A61K48/00 , C07K14/4738 , C07K2319/00
摘要： The INK4A (MTS1, CDKN2) gene encodes a specific inhibitor (InK4a-p16) of the cyclin D-dependent kinases CDK4 and CDK6. InK4a-p16 can block these kinase from phosphorylating the retinoblastoma protein (pRb), preventing exit from the G1 phase of the cell cycle. Deletions and mutations involving the gene encoding InK4a-p16, INK4A, occur frequently in cancer cells, implying that INK4a-p16, like pRb, suppresses tumor formulation. However, a completely unrelated protein (ARF-p19) arises in major part from an alternative reading frame of the mouse INK4A gene. Expression of an ARF-p19 cDNA (SEQ ID NO:1) in rodent fibroblasts induces both G1 and G2 phase arrest. Economical reutilization of protein coding sequences in this manner is without precedent in mammalian genomes, and the unitary inheritance of INK4a-p16 and ARF-p19 may reflect a dual requirement for both proteins in cell cycle control.

2. 发明授权

US06407062B1 ARF-P19, a novel regulator of the mammalian cell cycle 有权
标题翻译： ARF-P19是哺乳动物细胞周期的新型调节剂
公开(公告)号：US06407062B1
公开(公告)日：2002-06-18
申请号：US09480718
申请日：2000-01-07
申请人： Charles J. Sherr , Dawn Quelle , Martine F. Roussel , Frederique Zindy , Jason D. Weber
发明人： Charles J. Sherr , Dawn Quelle , Martine F. Roussel , Frederique Zindy , Jason D. Weber
IPC分类号： C07K1400
CPC分类号： C07K14/4738 , A01K2217/05 , A01K2217/075 , A61K38/00 , A61K48/00 , C07K14/4703 , C07K2319/00
摘要： The INK4A (MTS1, CDKN2) gene encodes a specific inhibitor (InK4a-p16) of the cyclin D-dependent kinases CDK4 and CDK6. InK4a-p16 can block these kinase from phosphorylating the retinoblastoma protein (pRb), preventing exit from the G1 phase of the cell cycle. Deletions and mutations involving the gene encoding InK4a-p16, INK4A, occur frequently in cancer cells, implying that INK4a-p16, like pRb, suppresses tumor formulation. However, a completely unrelated protein (ARF-p19) arises in major part from an alternative reading frame of the mouse INK4A gene. Expression of an ARF-p19 cDNA (SEQ ID NO:1) in rodent fibroblasts induces both G1 and G2 phase arrest. Economical reutilization of protein coding sequences in this manner is without precedent in mammalian genomes, and the unitary inheritance of INK4a-p16 and ARF-p19 may reflect a dual requirement for both proteins in cell cycle control.
摘要翻译： INK4A（MTS1，CDKN2）基因编码细胞周期蛋白D-依赖性激酶CDK4和CDK6的特异性抑制剂（InK4a-p16）。 InK4a-p16可以阻断这些激酶磷酸化视网膜母细胞瘤蛋白（pRb），从而阻止细胞周期的G1期退出。涉及编码InK4a-p16，INK4A的基因的缺失和突变频繁发生在癌细胞中，意味着像pRb一样的INK4a-p16抑制了肿瘤的制备。然而，完全不相关的蛋白质（ARF-p19）主要来自小鼠INK4A基因的替代阅读框架。 ARF-p19 cDNA（SEQ ID NO：1）在啮齿动物成纤维细胞中的表达诱导G1期和G2期停滞。蛋白质编码序列的经济再利用在哺乳动物基因组中是没有先例的，INK4a-p16和ARF-p19的单位遗传可能反映了细胞周期控制中两种蛋白质的双重要求。

3. 发明授权

US6046032A ARF-P19, a novel regulator of the mammalian cell cycle 失效
公开(公告)号：US6046032A
公开(公告)日：2000-04-04
申请号：US129855
申请日：1998-08-06
申请人： Charles J. Sherr , Dawn Quelle , Martine F. Roussel , Frederique Zindy
发明人： Charles J. Sherr , Dawn Quelle , Martine F. Roussel , Frederique Zindy
摘要： The INK4A (MTS1, CDKN2) gene encodes a specific inhibitor (InK4a-p16) of the cyclin D-dependent kinases CDK4 and CDK6. InK4a-p16 can block these kinase from phosphorylating the retinoblastoma protein (pRb), preventing exit from the G1 phase of the cell cycle. Deletions and mutations involving the gene encoding InK4a-p16, INK4A, occur frequently in cancer cells, implying that INK4a-p16, like pRb, suppresses tumor formulation. However, a completely unrelated protein (ARF-p19) arises in major part from an alternative reading frame of the mouse INK4A gene. Expression of an ARF-p19 cDNA (SEQ ID NO:1) in rodent fibroblasts induces both G1 and G2 phase arrest. Economical reutilization of protein coding sequences in this manner is without precedent in mammalian genomes, and the unitary inheritance of INK4a-p16 and ARF-p19 may reflect a dual requirement for both proteins in cell cycle control.

4. 发明授权

US06589505B1 Cells that lack p19ink4d and p27kip1 activity and methods of use thereof 有权
标题翻译：缺乏p19ink4d和p27kip1活性的细胞及其使用方法
公开(公告)号：US06589505B1
公开(公告)日：2003-07-08
申请号：US09483597
申请日：2000-01-14
申请人： Martine F. Roussel , Richard Smeyne , Frederique Zindy , Justine Cunningham , Neil Segil , Ping Chen
发明人： Martine F. Roussel , Richard Smeyne , Frederique Zindy , Justine Cunningham , Neil Segil , Ping Chen
IPC分类号： A61K4900
CPC分类号： C12N15/8509 , A01K67/0276 , A01K2217/075 , A01K2227/105 , A01K2267/03 , A01K2267/0356 , A61K49/0008 , C07K14/4738 , C12N2830/008 , C12N2840/203
摘要： Non-human animals that have been manipulated so as not to express a functional p19INK4d and p27KIP1 proteins are described. One particular non-human animal exemplified is a p19INK4d-double null, p27KIP1-double null mouse. Such knockout mice exhibit bradykinesia, proprioceptive abnormalities, seizure-like activity, and generally die 14-24 days after birth. In addition, mammalian cells having the p19INK4d-double null, p27KIP1-double null genotype are characterized. Methods of making and using the non-human knockout animals and cells are disclosed.
摘要翻译：描述了已经被操纵以便不表达功能性p19INK4d和p27KIP1蛋白质的非人类动物。一个特别的非人类动物是p19INK4d-双null，p27KIP1-双无效小鼠。这种敲除小鼠表现出运动迟缓，本体感觉异常，癫痫样活动，并且通常在出生后14-24天死亡。此外，具有p19INK4d-双null，p27KIP1-双无效基因型的哺乳动物细胞被表征。公开了制备和使用非人敲除动物和细胞的方法。

5. 发明授权

US06245965B1 Knockout mice and cells that lack p19INK4d and p27KIP1 activity and methods of use thereof 有权
标题翻译：敲除小鼠和缺乏p19INK4d和p27KIP1活性的细胞及其使用方法
公开(公告)号：US06245965B1
公开(公告)日：2001-06-12
申请号：US09240906
申请日：1999-01-29
申请人： Martine F. Roussel , Richard Smeyne , Frederique Zindy , Justine Cunningham
发明人： Martine F. Roussel , Richard Smeyne , Frederique Zindy , Justine Cunningham
IPC分类号： G01N3300
CPC分类号： C12N15/8509 , A01K67/0276 , A01K2217/075 , A01K2227/105 , A01K2267/0331 , A01K2267/0356 , C07K14/4738 , C12N2840/203
摘要： Non-human animals that have been manipulated so as not to express a functional p19INK4d and p27KIP1 proteins are described. One particulat non-human animal exemplified is a p19INK4d-double null, p27KIP1-double null mouse. Such knockout mice exhibit bradykinesia, proprioceptive abnormalties, seizure-like activity, and generally die 14-24 days after birth. In addition, mammalian cells having the p19INK4d-double null, p27KIP1-double null genotype are characterized. Methods of making and using the non-human knockout animals and cells are disclosed.
摘要翻译：描述了已经被操纵以便不表达功能性p19INK4d和p27KIP1蛋白质的非人类动物。一个特别的非人类动物是p19INK4d-双null，p27KIP1-双无效小鼠。这种敲除小鼠表现出运动迟缓，本体感觉异常，癫痫样活动，并且一般在出生后14-24天死亡。此外，具有p19INK4d-双null，p27KIP1-双无效基因型的哺乳动物细胞被表征。公开了制备和使用非人敲除动物和细胞的方法。

6. 发明授权

US6103887A Nucleotide sequence encoding human cyclin A 失效
标题翻译：编码人细胞周期蛋白A的核苷酸序列
公开(公告)号：US6103887A
公开(公告)日：2000-08-15
申请号：US210889
申请日：1998-12-15
申请人： Christian Brechot , Jian Wang , Xavier Chenivesse , Berthold Henglein , Frederique Zindy
发明人： Christian Brechot , Jian Wang , Xavier Chenivesse , Berthold Henglein , Frederique Zindy
IPC分类号： A61K38/00 , C07K14/47 , C07K16/18 , C12N15/113 , C12N15/12 , C07H21/04 , C12N15/11 , C12N15/63
CPC分类号： C12N15/113 , C07K14/4738 , C07K16/18 , A61K38/00 , C12N2310/3513
摘要： The invention is directed generally to a DNA sequence coding for human cyclin A and in particular to antibodies, or antisera including such antibodies, which bind to human cyclin A as encoded by the sequence of SEQ ID NO: 1 and which are useful in detecting cellular proliferation. The antibodies of the invention can be polyclonal or monoclonal, and are preferably generated by injection of purified human cyclin A into an animal host. The invention is particularly advantageous because it has been discovered that the gene encoding for human cyclin A is a site for integration of the hepatitis B virus associated with hepatocellular carcinoma, and by detecting human cyclin A through the use of the antibodies of the invention, one can detect and diagnose cell proliferation. Through the use of the present invention, cell proliferation and tumorigenesis can thus be detected at early stages, and such conditions can then be treated or inhibited by the use of anti-sense human cyclin A DNA.
摘要翻译：本发明一般涉及编码人类细胞周期蛋白A的DNA序列，特别是编码抗体或包含此类抗体的抗血清，其结合如SEQ ID NO：1的序列编码的人细胞周期蛋白A并且可用于检测细胞增殖。本发明的抗体可以是多克隆的或单克隆的，并且优选通过将纯化的人细胞周期蛋白A注射到动物宿主中来产生。本发明是特别有利的，因为已经发现编码人细胞周期蛋白A的基因是与肝细胞癌相关的乙型肝炎病毒整合的位点，并且通过使用本发明的抗体检测人细胞周期蛋白A 可以检测和诊断细胞增殖。通过使用本发明，因此可以在早期阶段检测细胞增殖和肿瘤发生，然后可以通过使用反义人细胞周期蛋白A DNA来治疗或抑制这些病症。

7. 发明授权

US5849508A Process for the detection of cell proliferation by detecting human cyclin A 失效
标题翻译：通过检测人细胞周期蛋白A检测细胞增殖的过程
公开(公告)号：US5849508A
公开(公告)日：1998-12-15
申请号：US460895
申请日：1995-06-05
申请人： Christian Brechot , Jian Wang , Xavier Chenivesse , Berthold Henglein , Frederique Zindy
发明人： Christian Brechot , Jian Wang , Xavier Chenivesse , Berthold Henglein , Frederique Zindy
IPC分类号： A61K38/00 , C07K14/47 , C07K16/18 , C12N15/113 , C12N15/12 , G01N33/574 , G01N33/53 , G01N33/567
CPC分类号： C12N15/113 , C07K14/4738 , C07K16/18 , A61K38/00 , C12N2310/3513
摘要： The invention is directed generally to a DNA sequence coding for human cyclin A and in particular to antibodies, or antisera including such antibodies, which bind to human cyclin A as encoded by the sequence of SEQ ID NO: 1 and which are useful in detecting cellular proliferation. The antibodies of the invention can be polyclonal or monoclonal, and are preferably generated by injection of purified human cyclin A into an animal host. The invention is particularly advantageous because it has been discovered that the gene encoding for human cyclin A is a site for integration of the hepatitis B virus associated with hepatocellular carcinoma, and by detecting human cyclin A through the use of the antibodies of the invention, one can detect and diagnose cell proliferation. Through the use of the present invention, cell proliferation and tumorigenesis can thus be detected at early stages, and such conditions can then be treated or inhibited by the use of anti-sense human cyclin A DNA.
摘要翻译：本发明一般涉及编码人类细胞周期蛋白A的DNA序列，特别是编码抗体或包含此类抗体的抗血清，其结合如SEQ ID NO：1的序列编码的人细胞周期蛋白A，并且其可用于检测细胞增殖。本发明的抗体可以是多克隆的或单克隆的，并且优选通过将纯化的人细胞周期蛋白A注射到动物宿主中来产生。本发明是特别有利的，因为已经发现编码人细胞周期蛋白A的基因是与肝细胞癌相关的乙型肝炎病毒整合的位点，并且通过使用本发明的抗体检测人细胞周期蛋白A 可以检测和诊断细胞增殖。通过使用本发明，因此可以在早期阶段检测细胞增殖和肿瘤发生，然后可以通过使用反义人细胞周期蛋白A DNA来治疗或抑制这些病症。

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