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1. 发明授权

US06063586A Diagnostic protocol 失效
标题翻译：诊断协议
公开(公告)号：US06063586A
公开(公告)日：2000-05-16
申请号：US18796
申请日：1998-02-04
申请人： Jennifer Rubin Grandis
发明人： Jennifer Rubin Grandis
IPC分类号： A61P35/00 , G01N33/567 , G01N33/574 , A61K39/395 , G01N33/53
CPC分类号： G01N33/5743 , G01N33/57492 , G01N2333/71
摘要： A cancer prognostic having particular utility in the prognosis of head and neck squamous cell cancer, in which the expression levels of either or both of Transforming Growth Factor Alpha (TGF-.alpha.) or Epidermal Growth Factor Receptor (EGFR) are assayed directly from a sample of tumor tissue. The expression level once quantitated is normalized as to standard, and the standardized expression level is compared to the prognostic threshold of about 83% of standard for TGF-.alpha. or of about 23% of standard for EGFR, or the corresponding upper threshold of the "low" tertile regardless of how calculated. Virtually all if not all patients demonstrating this low expression level survive at least five years after initial diagnosis, assuming completion of treatment with standard surgical tumor excision and radiation protocols for squamous cell head and neck cancer. Whether an individual patient's expression levels of TGF-.alpha. and EGFR fall inside or outside of this category signifies whether the patient is in a good or poor prognostic category, respectively, which in turn guides appropriate choice of therapy.
摘要翻译：在头颈部鳞状细胞癌的预后中具有特殊用途的癌症预后，其中直接从样品中检测转化生长因子α（TGF-α）或表皮生长因子受体（EGFR）中的任一者或两者的表达水平的肿瘤组织。定量表达水平与标准化相一致，标准化表达水平与TGF-α标准的约83％或EGFR标准的约23％的预后阈值相比较，或相应的“ 低“三分位数，无论如何计算。几乎所有如果不是全部，即使不是全部，表明这种低表达水平的患者在初步诊断后至少五年内存活，假设用标准手术肿瘤切除术和鳞状细胞头颈部癌症的辐射方案完成治疗。个体患者的TGF-α和EGFR表达水平是否落在此类别之内或之外，都意味着患者是否处于良好或不良预后类别，从而指导适当的治疗选择。

2. 发明授权

US09334496B2 Antisense EGFRAS guanidinium peptide nucleic acid (GPNA) oligonucleotides as antitumor agents 有权
标题翻译：反义EGFRAS胍基核酸（GPNA）寡核苷酸作为抗肿瘤剂
公开(公告)号：US09334496B2
公开(公告)日：2016-05-10
申请号：US13107344
申请日：2011-05-13
申请人： Jennifer Rubin Grandis , Sufi Mary Thomas , Danith H. Ly
发明人： Jennifer Rubin Grandis , Sufi Mary Thomas , Danith H. Ly
IPC分类号： C12N15/11 , C12N15/113
CPC分类号： C12N15/111 , C12N15/1138 , C12N2310/11 , C12N2310/3181 , C12N2320/51
摘要： A class of antisense agents having a distributed guanidinium peptide nucleic acids (GPNA) backbone which has excellent uptake into mammalian cells, can bind to the target DNA or RNA in a highly sequence specific manner and can resist nucleases and proteases both outside and inside the cell(s) of interest. In one embodiment, either systemic or intratumoral administration of antisense Epidermal Growth Factor Receptor (“EGFR”) GPNA oligonucleotides is believed to downmodulate EGFR levels, thus in turn to reduce head and neck squamous cell carcinoma tumor growth, which has been confirmed to date both in vitro and in vivo.
摘要翻译：具有对哺乳动物细胞摄取优异的分布的胍基肽核酸（GPNA）骨架的一类反义剂可以高度序列特异性的方式结合目标DNA或RNA，并可以抵抗细胞内外的核酸酶和蛋白酶（s）的兴趣。在一个实施方案中，全身或肿瘤内施用反义表皮生长因子受体（“EGFR”）GPNA寡核苷酸被认为下调EGFR水平，因此反过来降低头颈部鳞状细胞癌肿瘤生长，迄今为止已证实体外和体内。

3. 发明授权

US09370551B2 Compositions and methods of treating head and neck cancer 有权
标题翻译：治疗头颈癌的组合物和方法
公开(公告)号：US09370551B2
公开(公告)日：2016-06-21
申请号：US13557988
申请日：2012-07-25
申请人： Le Cong , Ann Marie Egloff , Levi A. Garraway , Jennifer Rubin Grandis , Eric S. Lander , Nicholas Stransky , Aaron D. Tward , Feng Zhang
发明人： Le Cong , Ann Marie Egloff , Levi A. Garraway , Jennifer Rubin Grandis , Eric S. Lander , Nicholas Stransky , Aaron D. Tward , Feng Zhang
IPC分类号： C12N15/85 , A61K38/16 , A61K38/46 , A61K45/06 , C07K14/47 , C12N9/22 , C12N15/90 , A61K48/00
CPC分类号： A61K38/164 , A61K38/465 , A61K45/06 , A61K48/005 , C07K14/4703 , C07K14/4705 , C07K2319/00 , C07K2319/70 , C07K2319/71 , C07K2319/80 , C12N9/22 , C12N15/907 , C12N2710/20011 , C12N2800/22 , C12N2999/007
摘要： The present invention provides methods related to the treatment of head and neck squamous cell carcinoma (HNSCC) and its associated premalignant lesions. In particular, the invention features methods which may specifically target HNSCC-associated genes and alter gene expression to treat or alleviate a symptom of HNSCC, or its related premalignant lesions. These methods may involve decreasing the function of an HNSCC-associated gene with aberrant gain-of-function; or increasing the function of an HNSCC-associated gene with aberrant loss-of-function.
摘要翻译：本发明提供了与头颈鳞状细胞癌（HNSCC）及其相关的恶化前病变相关的方法。特别地，本发明的特征在于可以特异性靶向HNSCC相关基因并改变基因表达以治疗或缓解HNSCC或其相关的恶化前病变的症状的方法。这些方法可能涉及降低具有异常增殖功能的HNSCC相关基因的功能; 或增加具有异常功能丧失的HNSCC相关基因的功能。

4. 发明授权

US07960360B2 Antisense guanidinium peptide nucleic acid (GPNA) oligonucleotides as antitumor agents 有权
标题翻译：反义胍胍核酸（GPNA）寡核苷酸作为抗肿瘤剂
公开(公告)号：US07960360B2
公开(公告)日：2011-06-14
申请号：US11939018
申请日：2007-11-13
申请人： Jennifer Rubin Grandis , Sufi Mary Thomas , Danith H. Ly
发明人： Jennifer Rubin Grandis , Sufi Mary Thomas , Danith H. Ly
IPC分类号： A01N43/04 , A61K31/70
CPC分类号： C12N15/111 , C12N15/1138 , C12N2310/11 , C12N2310/3181 , C12N2320/51
摘要： A class of antisense agents having a distributed guanidinium peptide nucleic acids (GPNA) backbone which has excellent uptake into mammalian cells, can bind to the target DNA or RNA in a highly sequence specific manner and can resist nucleases and proteases both outside and inside the cell(s) of interest. In one embodiment, either systemic or intratumoral administration of antisense Epidermal Growth Factor Receptor (“EGFR”) GPNA oligonucleotides is believed to downmodulate EGFR levels, thus in turn to reduce head and neck squamous cell carcinoma tumor growth, which has been confirmed to date both in vitro and in vivo.
摘要翻译：具有对哺乳动物细胞摄取优异的分布的胍基肽核酸（GPNA）骨架的一类反义剂可以高度序列特异性的方式结合目标DNA或RNA，并可以抵抗细胞内外的核酸酶和蛋白酶（s）的兴趣。在一个实施方案中，全身或肿瘤内施用反义表皮生长因子受体（“EGFR”）GPNA寡核苷酸被认为下调EGFR水平，因此反过来降低头颈部鳞状细胞癌肿瘤生长，迄今为止已证实体外和体内。

5. 发明申请

US20080234181A1 ANTISENSE GUANIDINIUM PEPTIDE NUCLEIC ACID (GPNA) OLIGONUCLEOTIDES AS ANTITUMOR AGENTS 有权
标题翻译：抗菌肽类核酸（GPNA）作为抗菌剂的寡核苷酸
公开(公告)号：US20080234181A1
公开(公告)日：2008-09-25
申请号：US11939018
申请日：2007-11-13
申请人： Jennifer Rubin GRANDIS , Sufi Mary THOMAS , Danith H. LY
发明人： Jennifer Rubin GRANDIS , Sufi Mary THOMAS , Danith H. LY
IPC分类号： A61K38/00 , C07K14/00 , A61P43/00
CPC分类号： C12N15/111 , C12N15/1138 , C12N2310/11 , C12N2310/3181 , C12N2320/51
摘要： A class of antisense agents having a distributed guanidinium peptide nucleic acids (GPNA) backbone which has excellent uptake into mammalian cells, can bind to the target DNA or RNA in a highly sequence specific manner and can resist nucleases and proteases both outside and inside the cell(s) of interest. In one embodiment, either systemic or intratumoral administration of antisense Epidermal Growth Factor Receptor (“EGFR”) GPNA oligonucleotides is believed to downmodulate EGFR levels, thus in turn to reduce head and neck squamous cell carcinoma tumor growth, which has been confirmed to date both in vitro and in vivo.
摘要翻译：具有对哺乳动物细胞摄取优异的分布的胍基肽核酸（GPNA）骨架的一类反义剂可以高度序列特异性的方式结合目标DNA或RNA，并可以抵抗细胞内外的核酸酶和蛋白酶（s）的兴趣。在一个实施方案中，全身或肿瘤内施用反义表皮生长因子受体（“EGFR”）GPNA寡核苷酸被认为下调EGFR水平，因此反过来降低头颈部鳞状细胞癌肿瘤生长，迄今为止已证实体外和体内。

6. 发明申请

US20130171124A1 Compositions And Methods Of Treating Head And Neck Cancer 有权
标题翻译：治疗头颈癌的组合和方法
公开(公告)号：US20130171124A1
公开(公告)日：2013-07-04
申请号：US13557988
申请日：2012-07-25
申请人： Le Cong , Ann Marie Egloff , Levi A. Garraway , Jennifer Rubin Grandis , Eric S. Lander , Nicholas Stransky , Aaron D. Tward , Feng Zhang
发明人： Le Cong , Ann Marie Egloff , Levi A. Garraway , Jennifer Rubin Grandis , Eric S. Lander , Nicholas Stransky , Aaron D. Tward , Feng Zhang
IPC分类号： A61K38/16 , A61K45/06 , A61K38/46
CPC分类号： A61K38/164 , A61K38/465 , A61K45/06 , A61K48/005 , C07K14/4703 , C07K14/4705 , C07K2319/00 , C07K2319/70 , C07K2319/71 , C07K2319/80 , C12N9/22 , C12N15/907 , C12N2710/20011 , C12N2800/22 , C12N2999/007
摘要： The present invention provides methods related to the treatment of head and neck squamous cell carcinoma (HNSCC) and its associated premalignant lesions. In particular, the invention features methods which may specifically target HNSCC-associated genes and alter gene expression to treat or alleviate a symptom of HNSCC, or its related premalignant lesions. These methods may involve decreasing the function of an HNSCC-associated gene with aberrant gain-of-function; or increasing the function of an HNSCC-associated gene with aberrant loss-of-function.
摘要翻译：本发明提供了与头颈鳞状细胞癌（HNSCC）及其相关的恶化前病变相关的方法。特别地，本发明的特征在于可以特异性靶向HNSCC相关基因并改变基因表达以治疗或缓解HNSCC或其相关的恶化前病变的症状的方法。这些方法可能涉及降低具有异常增殖功能的HNSCC相关基因的功能; 或增加具有异常功能丧失的HNSCC相关基因的功能。

7. 发明申请

US20110306562A1 Antisense EGFRAS Guanidinium Peptide Nucleic Acid (GPNA) Oligonucleotides as Antitumor Agents 有权
标题翻译：反义EGFRAS Guanidinium肽核酸（GPNA）寡核苷酸作为抗肿瘤剂
公开(公告)号：US20110306562A1
公开(公告)日：2011-12-15
申请号：US13107344
申请日：2011-05-13
申请人： Jennifer Rubin Grandis , Sufi Mary Thomas , Danith H. Ly
发明人： Jennifer Rubin Grandis , Sufi Mary Thomas , Danith H. Ly
IPC分类号： A61K38/02 , A61P35/00 , C07K2/00
CPC分类号： C12N15/111 , C12N15/1138 , C12N2310/11 , C12N2310/3181 , C12N2320/51
摘要： A class of antisense agents having a distributed guanidinium peptide nucleic acids (GPNA) backbone which has excellent uptake into mammalian cells, can bind to the target DNA or RNA in a highly sequence specific manner and can resist nucleases and proteases both outside and inside the cell(s) of interest. In one embodiment, either systemic or intratumoral administration of antisense Epidermal Growth Factor Receptor (“EGFR”) GPNA oligonucleotides is believed to downmodulate EGFR levels, thus in turn to reduce head and neck squamous cell carcinoma tumor growth, which has been confirmed to date both in vitro and in vivo.
摘要翻译：具有对哺乳动物细胞摄取优异的分布的胍基肽核酸（GPNA）骨架的一类反义剂可以高度序列特异性的方式结合目标DNA或RNA，并可以抵抗细胞内外的核酸酶和蛋白酶（s）的兴趣。在一个实施方案中，全身或肿瘤内施用反义表皮生长因子受体（“EGFR”）GPNA寡核苷酸被认为下调EGFR水平，因此反过来降低头颈部鳞状细胞癌肿瘤生长，迄今为止已证实体外和体内。

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