公开(公告)号：US07131482B2

公开(公告)日：2006-11-07

申请号：US10693351

申请日：2003-10-24

申请人： Mark Vincent ,  Sylvain Tremblay

发明人： Mark Vincent ,  Sylvain Tremblay

IPC分类号： B22D37/00

CPC分类号： B22D41/003 ,  B22C9/082 ,  B22D7/12 ,  B22D11/103 ,  B22D11/119 ,  B22D35/04 ,  B22D41/50 ,  C22B21/0084

摘要： A distributor device for use in aluminium casting includes a rigid, substantially bowl-shaped receptacle (2) of a refractory material having a base member (4) and a peripheral wall (6) that extends upwards from the base. The receptacle has an inlet opening (8) towards the upper end thereof and a pair of outlet openings (14) towards the base thereof. The device is constructed and arranged such that, in use, molten aluminium poured into the distributor device through the inlet opening (8) is redirected by the distributor device and flows outwards into the mould through the outlet openings (14).

公开(公告)号：US20060193367A1

公开(公告)日：2006-08-31

申请号：US10549947

申请日：2004-03-18

申请人： Mark Vincent

发明人： Mark Vincent

IPC分类号： H05B3/48

CPC分类号： F27D99/0006 ,  B22D11/117 ,  B22D11/119 ,  B22D41/01 ,  F27B17/00 ,  F27D3/14 ,  F27D11/00 ,  F27D21/0014

摘要： A continuous casting installation includes a furnace (2) for heating metal to a first liquid metal temperature, a degassing unit (4), a filter (6), a heating unit (8) and a casting machine (10). The casting machine (10) includes a pair of casting rollers and a nozzle arranged to deliver liquid metal into a nip between the casting rollers, such that the metal solidifies as it passes through the nip. The heating unit (8) is located between the furnace and the casting machine, and is thermostatically controlled to heat the liquid metal to a second liquid metal temperature.

摘要翻译： 连续铸造设备包括用于将金属加热到第一液态金属温度的炉（2），脱气单元（4），过滤器（6），加热单元（8）和浇铸机（10）。 铸造机（10）包括一对铸辊和喷嘴，其布置成将液态金属输送到铸辊之间的辊隙中，使得金属在其通过辊隙时固化。 加热单元（8）位于炉和铸造机之间，并被恒温控制以将液态金属加热至第二液态金属温度。

公开(公告)号：US20060135450A1

公开(公告)日：2006-06-22

申请号：US10510899

申请日：2003-04-08

申请人： D Koropatnick ,  Mark Vincent

发明人： D Koropatnick ,  Mark Vincent

IPC分类号： A61K48/00

CPC分类号： C12N15/1137 ,  A61K38/00 ,  C12N2310/315

摘要： Effective combinations of antisense oligonucleotides directed against thymidylate synthase mRNA are provided for use in cancer therapies. Combinations of antisense oligonucleotides have enhanced activity compared to the activity of the individual antisense oligonucleotides when used alone. The combinations may be used in conjunction with one or more chemotherapeutic agents to enhance the effects of the chemotherapeutic(s). Such antisense oligonucleotide combinations constitute improved antisense therapies with application to a variety of cancers or proliferative disorders, including drug resistant cancers.

摘要翻译： 提供针对胸苷酸合酶mRNA的反义寡核苷酸的有效组合用于癌症治疗。 当单独使用时，反义寡核苷酸的组合与单个反义寡核苷酸的活性相比具有增强的活性。 这些组合可以与一种或多种化学治疗剂结合使用以增强化学治疗剂的作用。 这样的反义寡核苷酸组合构成了可应用于多种癌症或增殖性疾病（包括耐药性癌症）的改进的反义治疗。

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。

公开(公告)号：US20050272683A1

公开(公告)日：2005-12-08

申请号：US11171435

申请日：2005-07-01

申请人： Donald Koropatnick ,  Mark Vincent ,  Nicholas Dean

发明人： Donald Koropatnick ,  Mark Vincent ,  Nicholas Dean

IPC分类号： C12N15/09 ,  A61K31/7088 ,  A61K38/00 ,  A61K48/00 ,  A61P35/00 ,  A61P43/00 ,  C12N9/10 ,  C12N15/113 ,  A61K31/522 ,  C07H21/02

CPC分类号： C12N15/1137 ,  A61K38/00 ,  C12N2310/111

摘要： Antisene oligonucleotides targeted to sequences in thymidylate synthase (TS) mRNA. In particular the invention relates to antisense oligonucleotides targeted to sequences in the 3′ end of TS mRNA, which are both cytostatic on their own when administered to human tumour cell lines, and which also enhance the toxicity of anticancer drugs such as Tomudex. The invention also relates to antisense oligonucleotides targeted to sequences at or near the translation start site at the 5′ end of TS mRNA which induce TS gene transcription and enhance cell growth. The invention further relates to a combination product comprising an antisense oligonucleotide in combination with an anticancer agent such as Tomudex (N-(5[N-3,4-dihydro-2-methyl-4-oxoquinazolin-6-ylmethyl)-N-methylamino]-2-thenoyl)-L-glutamic acid) or the Zeneca development compound ZD 9331 ((S)-2-(2-fluoro-4-[N-(4-hydroxy-2,7-dimethylquinazolin-6-ylmethyl)-N-(prop-2-ynyl)amino] benzamido-4-(1H-1,2,3,4-tetrazol-5-yl) butyric acid), and to the use of such a combination product in the treatment of cancer.

摘要翻译： 靶向胸苷酸合酶（TS）mRNA序列的反义寡核苷酸。 特别地，本发明涉及靶向TS mRNA的3'端的序列的反义寡核苷酸，当被给予人肿瘤细胞系时它们本身都是细胞抑制的，并且还增强抗肿瘤药物如Tomudex的毒性。 本发明还涉及针对诱导TS基因转录并增强细胞生长的TS mRNA的5'末端的翻译起始位点处或附近的序列的反义寡核苷酸。 本发明还涉及包含反义寡核苷酸与抗癌剂如Tomudex（N-（5-N，3,4-二氢-2-甲基-4-氧代喹唑啉-6-基甲基）-N- 甲基氨基] -2-噻吩甲酰基）-L-谷氨酸）或Zeneca显影化合物ZD 9331（（S）-2-（2-氟-4- [N-（4-羟基-2,7-二甲基喹唑啉-6-基） 吡啶-2-基甲基）-N-（丙-2-炔基）氨基]苯甲酰氨基-4-（1H-1,2,3,4-四唑-5-基）丁酸），以及这种组合产物在 治疗癌症。