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1. 发明申请

US20180195107A1 SRM Assay to Indicate Cancer Therapy 审中-公开
公开(公告)号：US20180195107A1
公开(公告)日：2018-07-12
申请号：US15837888
申请日：2017-12-11
申请人： EXPRESSION PATHOLOGY, INC.
发明人： David B. KRIZMAN , Todd HEMBROUGH , Sheeno THYPARAMBIL , Wei-Li LIAO
IPC分类号： C12Q1/37 , G01N33/574 , C12N9/10 , C12N9/12 , C07K16/40 , G01N33/68
CPC分类号： C12Q1/37 , C07K16/40 , C07K2317/34 , C12N9/1007 , C12N9/12 , C12Y201/01045 , C12Y207/10001 , G01N33/57484 , G01N33/6848 , G01N2560/00 , G01N2800/52 , G01N2800/56 , G01N2800/7028
摘要： The current disclosure provides for specific peptides, and derived ionization characteristics of the peptides, from the ALK, Ros, Ron, Ret, TS, and/or FGFR1 proteins that are particularly advantageous for quantifying the ALK, Ros, Ron, Ret, TS, and/or FGFR1 proteins directly in biological samples that have been fixed in formalin by the methods of Selected Reaction Monitoring (SRM) mass spectrometry, or as Multiple Reaction Monitoring (MRM) mass spectrometry. Such biological samples are chemically preserved and fixed wherein the biological sample is selected from tissues and cells treated with formaldehyde containing agents/fixatives including formalin-fixed tissue/cells, formalin-fixed/paraffin embedded (FFPE) tissue/cells, FFPE tissue blocks and cells from those blocks, and tissue culture cells that have been formalin fixed and or paraffin embedded. A protein sample is prepared from the biological sample using the Liquid Tissue™ reagents and protocol and the ALK, Ros, Ron, Ret, TS, and/or FGFR1 proteins are quantitated in the Liquid Tissue™ sample by the method of SRM/MRM mass spectrometry, by quantitating in the protein sample at least one or more of the peptides described. These peptides can be quantitated if they reside in a modified or an unmodified form. An example of a modified form of an ALK, Ros, Ron, Ret, TS, and/or FGFR1 fragment peptide is phosphorylation of a tyrosine, threonine, serine, and/or other amino acid residues within the peptide sequence.

2. 发明授权

US09611503B2 Escherichia coli cell line with thyA knockout and folA knockout 有权
公开(公告)号：US09611503B2
公开(公告)日：2017-04-04
申请号：US13996539
申请日：2012-02-09
申请人： Nattida Suwanakitti , Sastra Chaotheing , Yongyuth Yuthavong , Sumalee Kamchonwongpaisan
发明人： Nattida Suwanakitti , Sastra Chaotheing , Yongyuth Yuthavong , Sumalee Kamchonwongpaisan
IPC分类号： A61K38/00 , C12Q1/26 , C12N9/06 , C12N9/10 , C12N15/70
CPC分类号： C12Q1/26 , C12N9/003 , C12N9/1007 , C12N15/70 , C12Y201/01045
摘要： The objective of this invention is to create a double thyA folA knockout Escherichia coli (E. coli) strain for antifolate screening against DHFR of malaria and other parasites. This strain is used together with a plasmid expressing DHFR-TS from the desired pathogenic organism, which constitutes an anti-DHFR assay against the pathogenic organism of interest. The benefit of this invention is that there is no interference from either host DHFR or trimethoprim, a bacterial DHFR inhibitor. This tool is easy to use and maintain. It provides quick and reliable results as compared with conventional anti-malarial and anti-parasitic assays. This invention should facilitate discovery of new anti-DHFR compounds against malaria and other parasitic diseases.

3. 发明授权

US08524876B2 RNAi molecule targeting thymidylate synthase and application thereof 有权
标题翻译：靶向胸苷酸合酶的RNAi分子及其应用
公开(公告)号：US08524876B2
公开(公告)日：2013-09-03
申请号：US13258591
申请日：2010-03-29
申请人： Hiromi Wada , Cheng Long Huang
发明人： Hiromi Wada , Cheng Long Huang
IPC分类号： C07H21/04
CPC分类号： A61K31/7088 , A61K31/4412 , A61K31/513 , A61K31/53 , A61K45/06 , C12N15/1137 , C12N2310/14 , C12N2320/31 , C12Y201/01045 , A61K2300/00
摘要： This invention provides a novel RNAi molecule that can significantly potentiate antitumor effects of a 5-FU antitumor agent. The RNAi molecule comprises the nucleotide sequence shown in SEQ ID NO: 2. The invention also provides an antitumor agent comprising such RNAi molecule and a 5-FU antitumor agent.
摘要翻译：本发明提供了可显着增强5-FU抗肿瘤剂抗肿瘤作用的新型RNAi分子。 RNAi分子包含SEQ ID NO：2所示的核苷酸序列。本发明还提供包含这种RNAi分子和5-FU抗肿瘤剂的抗肿瘤剂。

4. 发明授权

US6087489A Antisense oligonucleotide modulation of human thymidylate synthase expression 失效
标题翻译：人胸苷酸合酶表达的反义寡核苷酸调节
公开(公告)号：US6087489A
公开(公告)日：2000-07-11
申请号：US89195
申请日：1998-06-02
申请人： Nicholas M. Dean
发明人： Nicholas M. Dean
IPC分类号： A61K38/00 , A61K45/06 , C12N15/113 , C07H21/04 , C12Q1/68
CPC分类号： C12N15/1137 , A61K45/06 , C12Y201/01045 , A61K38/00 , C12N2310/315 , C12N2310/321 , C12N2310/334 , C12N2310/341 , C12N2310/346
摘要： Compounds, compositions and methods are provided for modulating the expression of human thymidylate synthase. The compositions comprise antisense oligonucleotides targeted to nucleic acids encoding thymidylate synthase. Methods of using these oligonucleotides for modulation of thymidylate synthase expression and for treatment of diseases such as cancers believed to be responsive to modulation of thymidylate synthase expression are provided.
摘要翻译：提供化合物，组合物和方法用于调节人胸苷酸合酶的表达。组合物包含靶向编码胸苷酸合酶的核酸的反义寡核苷酸。提供了使用这些寡核苷酸调节胸苷酸合酶表达和治疗被认为对胸苷酸合酶表达的调节有反应的疾病的疾病的方法。

5. 发明申请

US20110150850A1 REDUCED COLONIZATION OF MICROBES AT THE MUCOSA 审中-公开
标题翻译：微生物在MUCOSA的降低的结合
公开(公告)号：US20110150850A1
公开(公告)日：2011-06-23
申请号：US12737929
申请日：2009-09-29
申请人： Lothar Steidler
发明人： Lothar Steidler
IPC分类号： A61K35/74 , C12N1/00 , C12N1/20 , C12N1/16 , C12N1/14 , C12N1/21 , C12N1/15 , C12N1/19 , A61K35/66 , A61P43/00
CPC分类号： C12N1/36 , A61K47/6901 , A61K2039/523 , A61K2039/542 , A61K2039/55594 , C12N9/1007 , C12P21/02 , C12Y201/01045
摘要： The invention is in the field of use of engineered microbes for the delivery and administration of therapeutic peptides or proteins to humans or animals suffering from a disease, or the use of engineered microbes for the delivery of antigens such as for vaccination purposes. More in particular, the invention relates to a recombinant microbe that has reduced capacity of colonizing the mucosa in comparison to its wild type ancestor, in particular when residing in the alimentary tract as part of a treatment or vaccination of a human or animal. In particular, the recombinant microbe contains an inactive thymidylate synthase gene that causes the reduced capability for the microbe to colonize in the alimentary tract. The invention also covers the use of said recombinant microbes comprising nucleic acids or vectors for expressing heterologous or homologous proteins; and also for delivery, especially therapeutic delivery, of the said proteins to animals or humans.
摘要翻译：本发明涉及使用工程微生物来递送和给予患有疾病的人或动物的治疗性肽或蛋白质，或者使用工程微生物来递送抗原，例如用于疫苗接种目的。更具体地，本发明涉及与其野生型祖先相比具有降低的粘膜能力的重组微生物，特别是当作为人或动物的治疗或疫苗接种的一部分驻留在消化道中时。特别地，重组微生物含有无活性的胸苷酸合酶基因，其导致微生物在消化道中定居的能力降低。本发明还涵盖了包含核酸或载体用于表达异源或同源蛋白质的所述重组微生物的用途; 并且还用于将所述蛋白质递送，特别是治疗性递送给动物或人。

6. 发明申请

US20110003879A1 Antisense oligonucleotides targeted to the coding region of thymidylate synthase and uses thereof 审中-公开
标题翻译：靶向胸苷酸合酶编码区的反义寡核苷酸及其用途
公开(公告)号：US20110003879A1
公开(公告)日：2011-01-06
申请号：US11908389
申请日：2006-03-13
申请人： Mark D. Vincent , D. James Koropatnick
发明人： Mark D. Vincent , D. James Koropatnick
IPC分类号： A61K31/7088 , C07H21/04 , A61P35/00
CPC分类号： C12N15/111 , C12N15/1137 , C12N2310/11 , C12N2310/315 , C12N2310/321 , C12N2310/341 , C12N2310/346 , C12N2320/31 , C12Y201/01045 , C12N2310/3521 , C12N2310/3525
摘要： Antisense oligonucleotides directed to the coding region of a mammalian thymidylate synthase mRNA that are capable of inhibiting the proliferation of cancer cells without decreasing the level of thymidylate synthase mRNA in the cells are provided. The antisense oligonucleotides are also capable of inducing apoptosis in the cancer cells. The antisense oligonucleotides can be used to inhibit the proliferation of cancer cells and to induce apoptosis in cancer cells. Methods of treating cancer, and in particular breast cancer, with the antisense oligonucleotides, alone or in combination with other therapeutics, are also provided.
摘要翻译：提供了针对能够抑制癌细胞增殖但不降低细胞中胸苷酸合酶mRNA水平的哺乳动物胸苷酸合酶mRNA编码区的反义寡核苷酸。反义寡核苷酸也能够诱导癌细胞凋亡。反义寡核苷酸可用于抑制癌细胞的增殖并诱导癌细胞凋亡。还提供了用反义寡核苷酸单独或与其它治疗剂组合治疗癌症，特别是乳腺癌的方法。

7. 发明申请

US20100135973A1 Microorganism Strain CRC2631 of Salmonella typhimurium and its Use as a Cancer Therapeutic 有权
标题翻译：鼠伤寒沙门氏菌的微生物菌株CRC2631及其作为癌症治疗用途
公开(公告)号：US20100135973A1
公开(公告)日：2010-06-03
申请号：US12472254
申请日：2009-05-26
申请人： Abraham Eisenstark , Robert A. Kazmierczak
发明人： Abraham Eisenstark , Robert A. Kazmierczak
IPC分类号： A61K45/00 , C12N1/20 , A61P35/00
CPC分类号： C12N9/1007 , C12Y201/01045
摘要： The present invention provides a biologically pure isolate of the genus Salmonella having a disruption of at least one gene selected from the group consisting of aroA, rfaH, and thyA, as well as a method of treating cancer including the step of administering such a Salmonella to a subject in need thereof.
摘要翻译：本发明提供具有破坏至少一种选自aroA，rfaH和thyA的基因的沙门氏菌属的生物纯纯分离物，以及治疗癌症的方法，包括给予这种沙门氏菌的步骤有需要的科目。

8. 发明申请

US20060089322A1 Antisense oligonucleotides for identifying drug targets and enhancing cancer therapies 审中-公开
标题翻译：用于鉴定药物靶标和增强癌症治疗的反义寡核苷酸
公开(公告)号：US20060089322A1
公开(公告)日：2006-04-27
申请号：US10513255
申请日：2003-05-01
申请人： Mark Vincent , Donald Koropatnick , Randall Berg
发明人： Mark Vincent , Donald Koropatnick , Randall Berg
IPC分类号： A61K48/00 , A61K31/7072 , A61K31/513 , C12Q1/68 , C07H21/04
CPC分类号： C12N15/1137 , A61K38/00 , C12N2310/315 , C12N2310/321 , C12N2310/341 , C12N2310/346 , C12Y102/01002 , C12Y201/01045 , C12N2310/3525
摘要： The present invention provides antisense oligonucleotides useful for identifying drug targets for cancer therapies and for enhancing current cancer therapies. The oligonucleotides of the invention are complementary to thymidylate synthase mRNA and affect expression of at least one other gene. For the enhancement of cancer therapies, such antisense oligonucleotides can be used in conjunction with standard chemotherapeutic agents in order to target thymidylate synthase, as well as other appropriate targets. The antisense oligonucleotides and the methods of the invention constitute improved antisense therapies with application to a variety of cancers.
摘要翻译：本发明提供了用于鉴定癌症疗法的药物靶标和用于增强目前的癌症疗法的反义寡核苷酸。本发明的寡核苷酸与胸苷酸合酶mRNA互补并影响至少一种其他基因的表达。为了增强癌症疗法，这种反义寡核苷酸可以与标准化学治疗剂结合使用，以靶向胸苷酸合酶以及其他合适的靶标。反义寡核苷酸和本发明的方法构成了应用于多种癌症的改进的反义治疗。

9. 发明授权

US06416987B1 Mutants of thymidylate synthase and uses thereof 失效
标题翻译：胸苷酸合酶的突变体及其用途
公开(公告)号：US06416987B1
公开(公告)日：2002-07-09
申请号：US09367007
申请日：1999-08-04
申请人： Xinyue Liu-Chen , Youzhi Tong , Joseph R. Bertino , Debabrata Banerjee
发明人： Xinyue Liu-Chen , Youzhi Tong , Joseph R. Bertino , Debabrata Banerjee
IPC分类号： C12N912
CPC分类号： C12N9/1007 , A61K38/00 , C12Y201/01045
摘要： The present invention provides a mutated human TS, said mutated synthase differing from wild type TS at amino acid residue 49, amino acid residue 52, amino acid residue 108, amino acid residue 221 or amino acid residue 225. Also provided is cDNA mutated human TSs and novel vectors and host cells and methods of using the mutated human TSs.
摘要翻译：本发明提供了突变的人TS，所述突变的合酶在氨基酸残基49，氨基酸残基52，氨基酸残基108，氨基酸残基221或氨基酸残基225处不同于野生型TS。还提供了cDNA突变人TS 和新型载体和宿主细胞以及使用突变的人类TSs的方法。

10. 发明授权

US09359605B2 Method of treating cancer by inhibition of DNA repair proteins 有权
标题翻译：通过抑制DNA修复蛋白治疗癌症的方法
公开(公告)号：US09359605B2
公开(公告)日：2016-06-07
申请号：US14004416
申请日：2012-03-12
申请人： Mark Vincent , Peter J. Ferguson , Mateusz Rytelewski
发明人： Mark Vincent , Peter J. Ferguson , Mateusz Rytelewski
IPC分类号： A61K48/00 , C07H21/02 , C07H21/04 , C12N15/113 , A61K31/7088 , A61K31/7105 , A61K31/7115
CPC分类号： C12N15/1135 , A61K31/198 , A61K31/282 , A61K31/502 , A61K31/513 , A61K31/7088 , A61K31/7105 , A61K31/7115 , A61K31/713 , A61K33/24 , C12N15/113 , C12N15/1137 , C12N2310/11 , C12N2310/14 , C12N2310/315 , C12N2310/321 , C12N2310/322 , C12N2310/341 , C12N2310/346 , C12N2320/31 , C12Y201/01045 , C12N2310/3521 , C12N2310/3525 , A61K2300/00
摘要： Methods of treating cancer using antisense oligonucleotides directed against DNA double-strand break repair proteins such as BRCA2 or RAD51 are provided. The antisense oligonucleotides can be used alone, in tandem or in combination with other cancer therapies, in particular with therapies that lead to DNA damage, inhibition of DNA repair or inhibition of DNA synthesis, such as radiation, platinum drugs, alkylating agents, PARP inhibitors, or inhibitors of thymidylate synthase.
摘要翻译：提供了使用针对DNA双链断裂修复蛋白（例如BRCA2或RAD51）的反义寡核苷酸治疗癌症的方法。反义寡核苷酸可以单独使用或与其他癌症治疗组合使用，特别是与导致DNA损伤，DNA修复抑制或DNA合成抑制的疗法，如放射线剂，铂药物，烷化剂，PARP抑制剂，或胸苷酸合酶抑制剂。

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