公开(公告)号：US20090304689A1

公开(公告)日：2009-12-10

申请号：US12364202

申请日：2009-02-02

Applicant: Arthur D. Levinson

Inventor： Arthur D. Levinson

IPC: A61K39/395 ,  G01N33/574 ,  C07K16/00 ,  A61P35/00

CPC classification number: G01N33/574 ,  A61K47/6803 ,  A61K47/6855

Abstract: Methods and compositions for the development of effective cancer therapies using mitotic inhibitors which have limited general toxicity to normal, non-cancerous cells and tissues are provided. The methods and compositions utilize cytotoxic compounds comprised of a cell-binding agent (e.g., antibodies) conjugated to an anti-mitotic compound (e.g., maytansinoids). The invention further provides antibodies which are substantially incapable of inducing antibody-dependent cell-mediated cytotoxicity (ADCC) and/or complement dependent cytotoxicity (CDC), thereby ensuring that the therapeutic effect is mediated primarily by the anti-mitotic component of the cytotoxic compound, rather than by indirect cell killing via ADCC and/or CDC. The antibodies of the invention further are capable of differentiating between polypeptide antigens which are more highly expressed on proliferating cancer cells as compared to proliferating non-cancer cells.

Abstract translation: 提供了使用对正常非癌细胞和组织具有有限的一般毒性的有丝分裂抑制剂来开发有效的癌症疗法的方法和组合物。 所述方法和组合物使用由与抗有丝分裂化合物（例如美登木素生物碱）缀合的细胞结合剂（例如抗体）组成的细胞毒性化合物。 本发明还提供基本上不能诱导抗体依赖性细胞介导的细胞毒性（ADCC）和/或补体依赖性细胞毒性（CDC）的抗体，从而确保治疗效果主要由细胞毒性化合物的抗有丝分裂成分介导 ，而不是通过ADCC和/或CDC的间接细胞杀伤。 与增殖的非癌细胞相比，本发明的抗体还能够区分在增殖性癌细胞上更高度表达的多肽抗原。

公开(公告)号：US06261837B1

公开(公告)日：2001-07-17

申请号：US09105412

申请日：1998-06-26

Applicant: Arthur D. Levinson ,  Diane Pennica ,  William J. Kohr ,  Gordon A. Vehar ,  David V. Goeddel ,  Elizabeth M. Yelverton ,  Christian C. Simonsen

Inventor： Arthur D. Levinson ,  Diane Pennica ,  William J. Kohr ,  Gordon A. Vehar ,  David V. Goeddel ,  Elizabeth M. Yelverton ,  Christian C. Simonsen

IPC: C12N516

CPC classification number: C12N9/0028 ,  C12N9/6459 ,  C12N15/85 ,  C12N2800/108 ,  C12N2830/00 ,  C12N2830/55 ,  C12Y304/21069

Abstract: A method for producing tissue plasminogen activator (t-PA) in eukaryotic host cells is disclosed. Enhanced levels of t-PA production are obtained by co-amplification of the t-PA gene through treatment of cultures transformed with mutant or wild type DHFR with methotrexate.

Abstract translation: 公开了一种在真核宿主细胞中产生组织纤溶酶原激活物（t-PA）的方法。 通过用甲氨蝶呤处理用突变体或野生型DHFR转化的培养物共同扩增t-PA基因，获得增强的t-PA产生水平。

公开(公告)号：US5424198A

公开(公告)日：1995-06-13

申请号：US162354

申请日：1993-12-03

Applicant: Arthur D. Levinson ,  Diane Pennica ,  William J. Kohr ,  Gordon A. Vehar ,  David V. Goeddel ,  Elizabeth M. Yelverton ,  Christian C. Simonsen

Inventor： Arthur D. Levinson ,  Diane Pennica ,  William J. Kohr ,  Gordon A. Vehar ,  David V. Goeddel ,  Elizabeth M. Yelverton ,  Christian C. Simonsen

IPC: C12N9/06 ,  C12N9/72 ,  C12N15/58 ,  C12N15/85 ,  C12P21/02 ,  C12N15/12

CPC classification number: C12N9/0028 ,  C12N15/85 ,  C12N9/6459 ,  C12Y304/21069 ,  C12N2800/108 ,  C12N2830/00 ,  C12N2830/55

Abstract: A method for producing tissue plasminogen activator (t-PA)in eukaroytic host cells is disclosed. Enhanced levels of t-PA production are obtained by co-amplification of the t-PA gene through treatment of cultures transformed with mutant or wild-type DHFR with methotrexate.

Abstract translation: 公开了一种用于在真核细胞宿主细胞中产生组织纤溶酶原激活物（t-PA）的方法。 通过用甲氨蝶呤处理用突变体或野生型DHFR转化的培养物共同扩增t-PA基因，获得增强的t-PA产生水平。

公开(公告)号：US5011795A

公开(公告)日：1991-04-30

申请号：US499201

申请日：1990-03-22

Applicant: Arthur D. Levinson ,  Diane Pennica ,  William J. Kohr ,  Gordon A. Vehar ,  David V. Goeddel ,  Elizabeth M. Yelverton ,  Christian C. Simonsen

Inventor： Arthur D. Levinson ,  Diane Pennica ,  William J. Kohr ,  Gordon A. Vehar ,  David V. Goeddel ,  Elizabeth M. Yelverton ,  Christian C. Simonsen

IPC: C12N9/06 ,  C12N9/72 ,  C12N15/58 ,  C12N15/85

CPC classification number: C12N9/0028 ,  C12N15/85 ,  C12N9/6459 ,  C12Y304/21069 ,  C12N2800/108 ,  C12N2840/20

Abstract: A method for producing tissue plasminogen activator (t-PA) in eukaryotic host cells is disclosed. Enhanced levels of t-PA production are obtained by co-amplification of the t-PA gene through treatment of cultures transformed with mutant or wild type DHFR with methotrexate.

Abstract translation: 公开了一种在真核宿主细胞中产生组织纤溶酶原激活物（t-PA）的方法。 通过用甲氨蝶呤处理用突变体或野生型DHFR转化的培养物共同扩增t-PA基因，获得增强的t-PA产生水平。

公开(公告)号：US4803164A

公开(公告)日：1989-02-07

申请号：US42604

申请日：1987-04-22

Applicant: Ronald A. Hitzeman ,  Arthur D. Levinson ,  Daniel G. Yansura

Inventor： Ronald A. Hitzeman ,  Arthur D. Levinson ,  Daniel G. Yansura

IPC: A61K39/29 ,  C07K14/02 ,  C12N15/81 ,  C12P21/00 ,  C12N15/00 ,  C12P21/02 ,  C12P21/04

CPC classification number: C07K14/005 ,  A61K39/12 ,  A61K39/292 ,  C12N15/81 ,  C12N2730/10122 ,  C12N2730/10134

Abstract: Hepatitis surface antigen is synthesized in recombinant yeast hosts transformed with vectors encoding hepatitis surface antigen, preferably under the control of the yeast PGK promoter and preferably in the absence of DNA encoding the surface antigen precursor. Hepatitis surface antigen is assembled by yeast into antigenic 22 nm particles even though hepatitis surface antigen bacterial transformants were not known to be capable of assembling the surface antigen into 22 nm particles.

Abstract translation: 在用编码肝炎表面抗原的载体转化的重组酵母宿主中合成肝炎表面抗原，优选在酵母PGK启动子的控制下，优选在不存在编码表面抗原前体的DNA的情况下。 尽管肝炎表面抗原细菌转化体不能将表面抗原组装成22纳米的颗粒，但肝炎表面抗原由酵母组装成抗原性22nm的颗粒。

公开(公告)号：USH2181H1

公开(公告)日：2007-02-06

申请号：US07663244

申请日：1991-02-28

Applicant: Arthur D. Levinson ,  Diane Pennica ,  William J. Kohr ,  Gordon A. Vehar ,  David V. Goeddel ,  Elizabeth M. Yelverton ,  Christian C. Simonsen

Inventor： Arthur D. Levinson ,  Diane Pennica ,  William J. Kohr ,  Gordon A. Vehar ,  David V. Goeddel ,  Elizabeth M. Yelverton ,  Christian C. Simonsen

IPC: C12N15/09

Abstract: A method for producing tissue plasminogen activator (t-PA) in eukaryotic host cells is disclosed. Enhanced levels of t-PA production are obtained by co-amplification of the t-PA gene through treatment of cultures transformed with mutant or wild-type DHFR with methotrexate.

公开(公告)号：US5849574A

公开(公告)日：1998-12-15

申请号：US450874

申请日：1995-05-26

Applicant: Arthur D. Levinson ,  Diane Pennica ,  William J. Kohr ,  Gordon A. Vehar ,  David V. Goeddel ,  Elizabeth M. Yelverton ,  Christian C. Simonsen

Inventor： Arthur D. Levinson ,  Diane Pennica ,  William J. Kohr ,  Gordon A. Vehar ,  David V. Goeddel ,  Elizabeth M. Yelverton ,  Christian C. Simonsen

IPC: C12N9/06 ,  C12N9/72 ,  C12N15/58 ,  C12N15/85

CPC classification number: C12N9/0028 ,  C12N15/85 ,  C12N9/6459 ,  C12Y304/21069 ,  C12N2800/108 ,  C12N2830/00 ,  C12N2830/55

Abstract: A method for producing tissue plasminogen activator (t-PA) in eukaryotic host cells is disclosed. Enhanced levels of t-PA production are obtained by co-amplification of the t-PA gene through treatment of cultures transformed with mutant or wild type DHFR with methotrexate.

Abstract translation: 公开了一种在真核宿主细胞中产生组织纤溶酶原激活物（t-PA）的方法。 通过用甲氨蝶呤处理用突变体或野生型DHFR转化的培养物共同扩增t-PA基因，获得增强的t-PA产生水平。

公开(公告)号：US4965199A

公开(公告)日：1990-10-23

申请号：US083758

申请日：1987-08-07

Applicant: Daniel J. Capon ,  Richard M. Lawn ,  Arthur D. Levinson ,  Gordon A. Vehar ,  William I. Wood

Inventor： Daniel J. Capon ,  Richard M. Lawn ,  Arthur D. Levinson ,  Gordon A. Vehar ,  William I. Wood

IPC: A61K38/00 ,  C07K14/755 ,  C12N15/10 ,  C12N15/12 ,  C12N15/62 ,  C12N15/85 ,  C12Q1/68

CPC classification number: C07K14/755 ,  C12N15/1034 ,  C12N15/62 ,  C12N15/85 ,  C12Q1/6832 ,  A61K38/00 ,  C07K2319/00 ,  C07K2319/02 ,  C07K2319/80 ,  C12N2800/108 ,  C12N2830/00 ,  C12N2830/55 ,  C12N2840/105 ,  C12N2840/44 ,  Y10S435/948 ,  Y10S930/10

Abstract: A method for producing factor VIII in recombinant mammalian host cells utilizing an expression vector containing a selectable marker DNA and an amplifiable marker DNA. The initial selection is based upon the selectable marker and subsequent amplification of factor VIII DNA and amplifiable marker DNA is conducted in cells not deficient in the amplifiable marker.

Abstract translation: 使用含有选择性标记DNA和可扩增标记DNA的表达载体在重组哺乳动物宿主细胞中产生VIII因子的方法。 初始选择基于选择标记和因子VIII DNA的随后扩增，并且可扩增标记DNA在不可扩增标记物缺陷的细胞中进行。

公开(公告)号：US4741901A

公开(公告)日：1988-05-03

申请号：US603529

申请日：1984-04-24

Applicant: Arthur D. Levinson ,  Chung-Cheng Liu ,  Daniel G. Yansura

Inventor： Arthur D. Levinson ,  Chung-Cheng Liu ,  Daniel G. Yansura

IPC: A61K39/00 ,  A61K39/29 ,  C07K14/02 ,  A61K39/12 ,  C07K13/00 ,  C12N1/00 ,  C12N5/00 ,  C12N15/00 ,  C12P21/00 ,  C12P21/02 ,  C12P21/04

CPC classification number: C07K14/005 ,  A61K39/12 ,  A61K39/292 ,  A61K2039/55555 ,  A61K39/00 ,  C12N2730/10122 ,  C12N2730/10134 ,  Y10S530/806 ,  Y10S530/826

Abstract: Novel vaccines are provided for immunization against hepatitis B surface antigen wherein the surface antigen is present in 22nm form but contains only mature hepatitis B surface antigen.

Abstract translation: 提供新型疫苗用于免疫乙型肝炎表面抗原，其中表面抗原以22nm形式存在，但仅含有成熟乙型肝炎表面抗原。

公开(公告)号：US5268291A

公开(公告)日：1993-12-07

申请号：US663103

申请日：1991-02-28

Applicant: Arthur D. Levinson ,  Diane Pennica ,  William J. Kohr ,  Gordon A. Vehar ,  David V. Goeddel ,  Christian C. Simonsen

Inventor： Arthur D. Levinson ,  Diane Pennica ,  William J. Kohr ,  Gordon A. Vehar ,  David V. Goeddel ,  Christian C. Simonsen

IPC: C12N9/06 ,  C12N9/72 ,  C12N15/58 ,  C12N15/85 ,  C12N5/10 ,  C12N5/16 ,  C12P21/02

CPC classification number: C12N9/0028 ,  C12N15/85 ,  C12N9/6459 ,  C12Y304/21069 ,  C12N2800/108 ,  C12N2830/00 ,  C12N2830/55

Abstract: A method for producing tissue plasminogen activator (t-PA) in eukaryotic host cells is disclosed. Enhanced levels of t-PA production are obtained by co-amplification of the t-PA gene through treatment of cultures transformed with mutant or wild-type DHFR with methotrexate.

Abstract translation: 公开了一种在真核宿主细胞中产生组织纤溶酶原激活物（t-PA）的方法。 通过用甲氨蝶呤处理用突变体或野生型DHFR转化的培养物共同扩增t-PA基因，获得增强的t-PA产生水平。