公开(公告)号：US07622630B2

公开(公告)日：2009-11-24

申请号：US10570116

申请日：2004-08-27

Applicant: Joerg Heyer ,  Murray Robinson ,  William Rideout, III ,  Ronald Depinho ,  Steven C. Clark ,  Yinghui Zhou ,  Tyler Jacks ,  Ronan C. O'Hagan

Inventor： Joerg Heyer ,  Murray Robinson ,  William Rideout, III ,  Ronald Depinho ,  Steven C. Clark ,  Yinghui Zhou ,  Tyler Jacks ,  Ronan C. O'Hagan

IPC: C12N15/00 ,  A01K67/00 ,  C12N5/06

CPC classification number: A01K67/0276 ,  A01K67/0271 ,  A01K2217/05 ,  A01K2217/075 ,  A01K2227/105 ,  A01K2267/0331 ,  C07K14/82 ,  C12N15/8509 ,  C12N2830/003

Abstract: Chimeric nonhuman mammals useful as inducible spontaneous cancer models are disclosed. The nonhuman mammals are obtained by introducing one or more genetically modified embryonic stem (ES) cells into an early stage embryo, and then implanting the manipulated embryo into a surrogate mother. The ES cells contain a recombinant oncogene, and also may contain a genetic mutation that deletes or inactivates a tumor suppressor gene. Models of different types of cancer are produced by introducing different combinations of genetic mutations into the ES cells that are introduced into the early stage embryo.

Abstract translation: 公开了可用作诱导型自发癌症模型的嵌合非人哺乳动物。 通过将一个或多个经遗传修饰的胚胎干细胞（ES）细胞引入早期胚胎，然后将操作的胚胎植入替代母体中获得非人类哺乳动物。 ES细胞含有重组癌基因，并且还可能含有遗传突变，其删除或灭活肿瘤抑制基因。 不同类型癌症的模型是通过将遗传突变的不同组合引入引入早期胚胎的ES细胞来产生的。

公开(公告)号：US06348191B1

公开(公告)日：2002-02-19

申请号：US07704578

申请日：1991-06-17

Applicant: Steven C. Clark ,  Gordon G. Wong ,  Paul Schendel ,  John McCoy

Inventor： Steven C. Clark ,  Gordon G. Wong ,  Paul Schendel ,  John McCoy

IPC: A61K3820

CPC classification number: C07K14/5412 ,  A61K38/2013 ,  A61K38/204 ,  A61K38/217 ,  A61K39/395 ,  A61K2300/00

Abstract: IL-6 is produced via recombinant DNA techniques. The peptide is useful in the treatment of disorders characterized by deficiencies in hematopoietic cells and in combination with other hematopoietins in cancer therapies.

Abstract translation: 通过重组DNA技术产生IL-6。 该肽可用于治疗以造血细胞缺陷为特征的疾病，并与癌症治疗中的其它造血素组合。

公开(公告)号：US5942221A

公开(公告)日：1999-08-24

申请号：US468694

申请日：1995-06-06

Applicant: Steven C. Clark ,  Randal J. Kaufman ,  Gordon G. Wong

Inventor： Steven C. Clark ,  Randal J. Kaufman ,  Gordon G. Wong

IPC: C12P21/02 ,  A61K38/00 ,  A61K38/17 ,  C07K14/535 ,  C12N15/27 ,  C12N15/70 ,  C12N15/81 ,  C12N15/85 ,  A61K38/19

CPC classification number: C07K14/535 ,  C12N15/70 ,  C12N15/81 ,  C12N15/85 ,  A61K38/00 ,  C12N2830/42 ,  C12N2840/105 ,  Y10S514/885

Abstract: A method for preparing and isolating a transformation vector containing CSF/cDNA is described. The method comprises: preparing RNA from a cell that produces CSF; preparing polyadenylated messenger RNA from said RNA; preparing single stranded cDNA from said messenger RNA; converting the single stranded cDNA to double stranded cDNA; inserting the double stranded cDNA into transformation vectors and transforming bacteria with said vector to form colonies; picking pools of 200 to 500 colonies each and isolating plasmid DNA from each pool; transfecting the plasmid DNA into suitable host cells for expressing CSF protein; culturing the transfected cells and assaying the supernatant for CSF activity; and selecting CSF positive pools and screening the colonies used to make the pool to identify a colony having CSF activity. Also described are a cDNA coding for a protein having CSF activity (i.e. CSF/cDNA), a microorganism or cell line transformed with a recombinant vector containing such CSF/cDNA, and a method for producing CSF protein by expressing said CSF/cDNA by culturing a microorganism or cell line.

Abstract translation: 描述了制备和分离含有CSF / cDNA的转化载体的方法。 该方法包括：从产生CSF的细胞制备RNA; 从所述RNA制备聚腺苷酸化的信使RNA; 从所述信使RNA制备单链cDNA; 将单链cDNA转化为双链cDNA; 将双链cDNA插入转化载体并用所述载体转化细菌以形成菌落; 分别取200至500个菌落的池，每个池中分离出质粒DNA; 将质粒DNA转染到合适的宿主细胞中以表达CSF蛋白; 培养转染的细胞并测定上清液的CSF活性; 并选择CSF阳性池并筛选用于制备池的菌落以鉴定具有CSF活性的菌落。 还描述了编码具有CSF活性的蛋白质（即CSF / cDNA）的cDNA，用含有这种CSF / cDNA的重组载体转化的微生物或细胞系，以及通过培养表达所述CSF / cDNA来产生CSF蛋白的方法 微生物或细胞系。

公开(公告)号：US5648467A

公开(公告)日：1997-07-15

申请号：US403013

申请日：1995-03-13

Applicant: Giorgio Trinchieri ,  Bice Perussia ,  Steven C. Clark ,  Gordon G. Wong ,  Rodney Hewick ,  Michiko Kobayashi ,  Stanley F. Wolf

Inventor： Giorgio Trinchieri ,  Bice Perussia ,  Steven C. Clark ,  Gordon G. Wong ,  Rodney Hewick ,  Michiko Kobayashi ,  Stanley F. Wolf

IPC: A61K38/00 ,  A61K38/22 ,  A61K39/395 ,  A61P31/00 ,  A61P31/04 ,  A61P31/12 ,  A61P31/18 ,  A61P35/00 ,  A61P35/02 ,  A61P37/04 ,  A61P43/00 ,  C07K1/16 ,  C07K1/20 ,  C07K1/22 ,  C07K14/00 ,  C07K14/435 ,  C07K14/52 ,  C07K14/54 ,  C07K16/24 ,  C12N1/21 ,  C12N5/00 ,  C12N5/10 ,  C12N15/00 ,  C12N15/09 ,  C12N15/19 ,  C12N15/26 ,  C12P21/00 ,  C12P21/02 ,  C12R1/19 ,  C12R1/91 ,  G01N33/53 ,  A61K38/20

CPC classification number: C07K14/5434 ,  A61K38/00 ,  Y10S435/803 ,  Y10S514/885

Abstract: A novel homogeneous human cytokine, Natural Killer Stimulatory Factor, having the ability to induce the production of gamma interferon in vitro in human peripheral blood lymphocytes, and a pharmaceutical preparation containing it.

Abstract translation: 具有诱导在人外周血淋巴细胞体外产生γ干扰素的能力的新型均质人细胞因子，天然杀伤刺激因子，以及含有它的药物制剂。

公开(公告)号：US5437863A

公开(公告)日：1995-08-01

申请号：US115680

申请日：1993-09-01

Applicant: David A. Williams ,  Steven C. Clark

Inventor： David A. Williams ,  Steven C. Clark

IPC: A61K38/00 ,  A61K38/18 ,  A61K38/20 ,  A61P1/00 ,  A61P43/00 ,  C07K14/54 ,  C12N9/02 ,  A61K38/19

CPC classification number: C07K14/5431 ,  A61K38/204 ,  C12N9/0036 ,  C12Y108/01008 ,  A61K38/00 ,  Y10S514/867 ,  Y10S514/908

Abstract: A method of restoring damaged or depleted cell populations by treating the patient with cytokines, particularly IL-11 and IL-6.

Abstract translation: 通过用细胞因子特别是IL-11和IL-6治疗患者来恢复损伤或消耗细胞群的方法。

公开(公告)号：US4879227A

公开(公告)日：1989-11-07

申请号：US860377

申请日：1986-05-06

Applicant: Steven C. Clark ,  Gordon G. Wong

Inventor： Steven C. Clark ,  Gordon G. Wong

IPC: A61K38/00 ,  C07K14/53 ,  C12N15/27

CPC classification number: C07K14/53 ,  A61K38/00

Abstract: A process for producing a novel protein, CSF-69, is provided. The protein is capable of stimulating proliferation of monocytic lineage types cells in vitro assays. A novel DNA sequence codes on expression for CSF-69.

Abstract translation: 提供了一种生产新型蛋白质CSF-69的方法。 该蛋白能够在体外测定中刺激单核细胞谱系型细胞的增殖。 一种新的DNA序列编码CSF-69的表达。

公开(公告)号：US4868119A

公开(公告)日：1989-09-19

申请号：US940362

申请日：1986-12-11

Applicant: Steven C. Clark ,  Gordon G. Wong

Inventor： Steven C. Clark ,  Gordon G. Wong

IPC: A61K38/00 ,  C07K14/53 ,  C12N1/21

CPC classification number: C07K14/53 ,  A61K38/00 ,  Y10S930/12

Abstract: A novel family of primate CSF-1-like polypeptides is provided via recombinant techniques.

Abstract translation: 灵长类CSF-1样多肽的新家族通过重组技术提供。

公开(公告)号：US07030223B2

公开(公告)日：2006-04-18

申请号：US10124557

申请日：2002-04-16

Applicant: Katherine Turner ,  Steven C. Clark ,  Kenneth Jacobs ,  Rodney M. Hewick ,  Thomas G. Gesner

Inventor： Katherine Turner ,  Steven C. Clark ,  Kenneth Jacobs ,  Rodney M. Hewick ,  Thomas G. Gesner

IPC: C07K14/475 ,  C07K14/47 ,  C12N15/12 ,  C12P21/02

CPC classification number: C07K14/53 ,  A61K38/00

Abstract: Novel polypeptides of human megakaryocyte stimulating factors (MSFs). Pharmaceutical compositions containing same, and methods for their preparation and use are provided.

公开(公告)号：US5891429A

公开(公告)日：1999-04-06

申请号：US466308

申请日：1995-06-06

Applicant: Steven C. Clark ,  Randal J. Kaufman ,  Gordon G. Wong ,  Elizabeth A. Wang

Inventor： Steven C. Clark ,  Randal J. Kaufman ,  Gordon G. Wong ,  Elizabeth A. Wang

IPC: A61K38/00 ,  C07K14/535 ,  C12N15/27 ,  C12N15/70 ,  C12N15/81 ,  C12N15/85 ,  A61K38/19 ,  C07K1/20

CPC classification number: C12N15/85 ,  C07K14/535 ,  C12N15/70 ,  C12N15/81 ,  A61K38/00 ,  C12N2800/206 ,  C12N2830/00 ,  C12N2830/702 ,  C12N2840/105 ,  C12N2840/44

Abstract: A method for preparing and isolating a transformation vector containing CSF/cDNA is described. The method comprises:preparing RNA from a cell that produces CSF;preparing polyadenylated messenger RNA from said RNA;preparing single stranded cDNA from said messenger RNA;converting the single stranded cDNA to double stranded cDNA;inserting the double stranded cDNA into transformation vectors and transforming bacteria with said vector to form colonies;picking pools of 200 to 500 colonies each and isolating plasmid DNA from each pool;transfecting the plasmid DNA into suitable host cells for expressing CSF protein;culturing the transfected cells and assaying the supernatant for CSF activity; andselecting CSF positive pools and screening the colonies used to make the pool to identify a colony having CSF activity. Also described are a cDNA coding for a protein having CSF activity (i.e. CSF/cDNA), a microorganism or cell line transformed with a recombinant vector containing such CSF/cDNA, and a method for producing CSF protein by expressing said CSF/cDNA by culturing a microorganism or cell line. The invention also provides a method of purifying the CSF proteins and the purified proteins so produced.

Abstract translation: 描述了制备和分离含有CSF / cDNA的转化载体的方法。 该方法包括：从产生CSF的细胞制备RNA; 从所述RNA制备聚腺苷酸化的信使RNA; 从所述信使RNA制备单链cDNA; 将单链cDNA转化为双链cDNA; 将双链cDNA插入转化载体并用所述载体转化细菌以形成菌落; 分别取200至500个菌落的池，每个池中分离出质粒DNA; 将质粒DNA转染到合适的宿主细胞中以表达CSF蛋白; 培养转染的细胞并测定上清液的CSF活性; 并选择CSF阳性池并筛选用于制备池的菌落以鉴定具有CSF活性的菌落。 还描述了编码具有CSF活性的蛋白质（即CSF / cDNA）的cDNA，用含有这种CSF / cDNA的重组载体转化的微生物或细胞系，以及通过培养表达所述CSF / cDNA来产生CSF蛋白的方法 微生物或细胞系。 本发明还提供了纯化CSF蛋白质和如此制备的纯化蛋白质的方法。

公开(公告)号：US5734037A

公开(公告)日：1998-03-31

申请号：US647169

申请日：1996-05-09

Applicant: Yu-Chung Yang ,  Agnes Brennan Ciarletta ,  Susan Teresa Ricciardi ,  Steven C. Clark ,  Robert E. Donahue

Inventor： Yu-Chung Yang ,  Agnes Brennan Ciarletta ,  Susan Teresa Ricciardi ,  Steven C. Clark ,  Robert E. Donahue

IPC: A61K38/00 ,  A61K38/22 ,  A61P7/00 ,  A61P7/06 ,  A61P35/00 ,  A61P43/00 ,  C07K14/00 ,  C07K14/435 ,  C07K14/505 ,  C07K14/52 ,  C07K14/525 ,  C07K14/53 ,  C07K14/535 ,  C07K14/54 ,  C07K14/545 ,  C07K14/55 ,  C07K16/00 ,  C12N1/21 ,  C12N5/10 ,  C12N15/09 ,  C12N15/24 ,  C12P21/02 ,  C12P21/08 ,  C12R1/91

CPC classification number: C07K14/5425 ,  A61K38/00

Abstract: This invention provides a novel human erythropoietic growth factor and processes for producing it by recombinant DNA genetic engineering techniques.

Abstract translation: 本发明提供了一种新的人类红细胞生成因子及其通过重组DNA遗传工程技术生产的方法。