公开(公告)号：US07566777B2

公开(公告)日：2009-07-28

申请号：US10617561

申请日：2003-07-11

申请人： Frederick M. Enright ,  Jesse M. Jaynes ,  William Hansel ,  Kenneth L. Koonce ,  Samuel M. McCann ,  Wen H. Yu ,  Patricia A. Melrose ,  Lane D. Foil ,  Philip H. Elzer

发明人： Frederick M. Enright ,  Jesse M. Jaynes ,  William Hansel ,  Kenneth L. Koonce ,  Samuel M. McCann ,  Wen H. Yu ,  Patricia A. Melrose ,  Lane D. Foil ,  Philip H. Elzer

IPC分类号： C07H21/04 ,  C07H21/02 ,  C12P21/06 ,  C12P21/04 ,  C12N15/09

CPC分类号： C12N15/8257 ,  A61K38/00 ,  C07K7/23 ,  C07K14/43563 ,  C07K14/575 ,  C07K14/59 ,  C07K19/00 ,  C07K2319/00

摘要： Amphipathic lytic peptides are ideally suited to use in a ligand/cytotoxin combination to specifically inhibit cells that are driven by or are dependent upon a specific ligand interaction; for example, to induce sterility or long-term contraception, or to attack tumor cells, or to selectively lyse virally-infected cells, or to attack lymphocytes responsible for autoimmune diseases. The peptides act directly on cell membranes, and need not be internalized. Administering a combination of gonadotropin-releasing hormone (GnRH) (or a GnRH agonist) and a membrane-active lytic peptide produces long-term contraception or sterilization in animals in vivo. Administering in vivo a combination of a ligand and a membrane-active lytic peptide kills cells with a receptor for the ligand. The compounds are relatively small, and are not antigenic. Lysis of gonadotropes has been observed to be very rapid (on the order of ten minutes.) Lysis of tumor cells is rapid. The two components—the ligand and the lytic peptide—may optionally be administered as a fusion peptide, or they may be administered separately, with the ligand administered slightly before the lytic peptide, to activate cells with receptors for the ligand, and thereby make those cells susceptible to lysis by the lytic peptide. The compounds may be used in gene therapy to treat malignant or non-malignant tumors, and other diseases caused by clones or populations of “normal” host cells bearing specific receptors (such as lymphocytes), because genes encoding a lytic peptide or encoding a lytic peptide/peptide hormone fusion may readily be inserted into hematopoietic stem cells or myeloid precursor cells.

摘要翻译： 两亲性溶解肽理想地适用于配体/细胞毒素组合以特异性抑制由特定配体相互作用驱动或依赖于特定配体相互作用的细胞; 例如，诱导不育或长期避孕，或攻击肿瘤细胞，或选择性裂解病毒感染的细胞，或攻击负责自身免疫性疾病的淋巴细胞。 肽直接作用于细胞膜上，不需要内化。 管理促性腺激素释放激素（GnRH）（或GnRH激动剂）和膜活性溶解肽的组合在体内产生长期的动物避孕或灭菌。 在体内施用配体和膜活性裂解肽的组合将细胞与配体的受体杀死。 化合物相对较小，不具抗原性。 已经观察到促性腺激素的裂解非常快（十分钟左右）。肿瘤细胞裂解很快。 两种组分 - 配体和溶解肽 - 可以任选地作为融合肽施用，或者它们可以分开施用，配体在裂解肽之前略微施用，以激活配体受体的细胞，从而使得 易溶于裂解肽的细胞。 这些化合物可以用于治疗恶性或非恶性肿瘤的基因治疗，以及由具有特异性受体（如淋巴细胞）的“正常”宿主细胞的克隆或群体引起的其它疾病，因为编码溶解肽或编码溶酶体的基因 肽/肽激素融合可容易地插入到造血干细胞或骨髓前体细胞中。

公开(公告)号：US08258100B2

公开(公告)日：2012-09-04

申请号：US12488353

申请日：2009-06-19

申请人： Frederick M. Enright ,  Jesse M. Jaynes ,  William Hansel ,  Kenneth L. Koonce ,  Samuel M. McCann ,  Wen H. Yu ,  Patricia A. Melrose ,  Lane D. Foil ,  Philip H. Elzer

发明人： Frederick M. Enright ,  Jesse M. Jaynes ,  William Hansel ,  Kenneth L. Koonce ,  Samuel M. McCann ,  Wen H. Yu ,  Patricia A. Melrose ,  Lane D. Foil ,  Philip H. Elzer

IPC分类号： A61K38/00 ,  A61K38/25

CPC分类号： C12N15/8257 ,  A61K38/00 ,  C07K7/23 ,  C07K14/43563 ,  C07K14/575 ,  C07K14/59 ,  C07K19/00 ,  C07K2319/00

摘要： Amphipathic lytic peptides are ideally suited to use in a ligand/cytotoxin combination to specifically inhibit cells that are driven by or are dependent upon a specific ligand interaction; for example, to induce sterility or long-term contraception, or to attack tumor cells, or to selectively lyse virally-infected cells, or to attack lymphocytes responsible for autoimmune diseases. The peptides act directly on cell membranes, and need not be internalized. Administering a combination of gonadotropin-releasing hormone (GnRH) (or a GnRH agonist) and a membrane-active lytic peptide produces long-term contraception or sterilization in animals in vivo. Administering in vivo a combination of a ligand and a membrane-active lytic peptide kills cells with a receptor for the ligand. The compounds are relatively small, and are not antigenic. Lysis of gonadotropes has been observed to be very rapid (on the order of ten minutes.) Lysis of tumor cells is rapid. The two components—the ligand and the lytic peptide—may optionally be administered as a fusion peptide, or they may be administered separately, with the ligand administered slightly before the lytic peptide, to activate cells with receptors for the ligand, and thereby make those cells susceptible to lysis by the lytic peptide. The compounds may be used in gene therapy to treat malignant or non-malignant tumors, and other diseases caused by clones or populations of “normal” host cells bearing specific receptors (such as lymphocytes), because genes encoding a lytic peptide or encoding a lytic peptide/peptide hormone fusion may readily be inserted into hematopoietic stem cells or myeloid precursor cells.

摘要翻译： 两亲性溶解肽理想地适用于配体/细胞毒素组合以特异性抑制由特定配体相互作用驱动或依赖于特定配体相互作用的细胞; 例如，诱导不育或长期避孕，或攻击肿瘤细胞，或选择性裂解病毒感染的细胞，或攻击负责自身免疫性疾病的淋巴细胞。 肽直接作用于细胞膜上，不需要内化。 管理促性腺激素释放激素（GnRH）（或GnRH激动剂）和膜活性溶解肽的组合在体内产生长期的动物避孕或灭菌。 在体内施用配体和膜活性裂解肽的组合将细胞与配体的受体杀死。 化合物相对较小，不具抗原性。 已经观察到促性腺激素的裂解非常快（十分钟左右）。肿瘤细胞裂解很快。 两种组分 - 配体和溶解肽 - 可以任选地作为融合肽施用，或者它们可以分开施用，配体在裂解肽之前略微施用，以激活配体受体的细胞，从而使得 易溶于裂解肽的细胞。 这些化合物可以用于治疗恶性或非恶性肿瘤的基因治疗，以及由具有特异性受体（如淋巴细胞）的“正常”宿主细胞的克隆或群体引起的其它疾病，因为编码溶解肽或编码溶酶体的基因 肽/肽激素融合可容易地插入到造血干细胞或骨髓前体细胞中。

公开(公告)号：US20100016227A1

公开(公告)日：2010-01-21

申请号：US12488353

申请日：2009-06-19

申请人： FREDERICK M. ENRIGHT ,  JESSE M. JAYNES ,  WILLIAM HANSEL ,  KENNETH L. KOONCE ,  SAMUEL M. MCCANN ,  WEN H. YU ,  PATRICIA A. MELROSE ,  LANE D. FOIL ,  PHILIP H. ELZER

发明人： FREDERICK M. ENRIGHT ,  JESSE M. JAYNES ,  WILLIAM HANSEL ,  KENNETH L. KOONCE ,  SAMUEL M. MCCANN ,  WEN H. YU ,  PATRICIA A. MELROSE ,  LANE D. FOIL ,  PHILIP H. ELZER

IPC分类号： A61K38/22 ,  A61P35/04

CPC分类号： C12N15/8257 ,  A61K38/00 ,  C07K7/23 ,  C07K14/43563 ,  C07K14/575 ,  C07K14/59 ,  C07K19/00 ,  C07K2319/00

摘要： Amphipathic lytic peptides are ideally suited to use in a ligand/cytotoxin combination to specifically inhibit cells that are driven by or are dependent upon a specific ligand interaction; for example, to induce sterility or long-term contraception, or to attack tumor cells, or to selectively lyse virally-infected cells, or to attack lymphocytes responsible for autoimmune diseases. The peptides act directly on cell membranes, and need not be internalized. Administering a combination of gonadotropin-releasing hormone (GnRH) (or a GnRH agonist) and a membrane-active lytic peptide produces long-term contraception or sterilization in animals in vivo. Administering in vivo a combination of a ligand and a membrane-active lytic peptide kills cells with a receptor for the ligand. The compounds are relatively small, and are not antigenic. Lysis of gonadotropes has been observed to be very rapid (on the order of ten minutes.) Lysis of tumor cells is rapid. The two components—the ligand and the lytic peptide—may optionally be administered as a fusion peptide, or they may be administered separately, with the ligand administered slightly before the lytic peptide, to activate cells with receptors for the ligand, and thereby make those cells susceptible to lysis by the lytic peptide. The compounds may be used in gene therapy to treat malignant or non-malignant tumors, and other diseases caused by clones or populations of “normal” host cells bearing specific receptors (such as lymphocytes), because genes encoding a lytic peptide or encoding a lytic peptide/peptide hormone fusion may readily be inserted into hematopoietic stem cells or myeloid precursor cells.

摘要翻译： 两亲性溶解肽理想地适用于配体/细胞毒素组合以特异性抑制由特定配体相互作用驱动或依赖于特定配体相互作用的细胞; 例如，诱导不育或长期避孕，或攻击肿瘤细胞，或选择性裂解病毒感染的细胞，或攻击负责自身免疫性疾病的淋巴细胞。 肽直接作用于细胞膜上，不需要内化。 管理促性腺激素释放激素（GnRH）（或GnRH激动剂）和膜活性溶解肽的组合在体内产生长期的动物避孕或灭菌。 在体内施用配体和膜活性裂解肽的组合将细胞与配体的受体杀死。 化合物相对较小，不具抗原性。 已经观察到促性腺激素的裂解非常快（十分钟左右）。肿瘤细胞裂解很快。 两种组分 - 配体和溶解肽 - 可以任选地作为融合肽施用，或者它们可以分开施用，配体在裂解肽之前略微施用，以激活配体受体的细胞，从而使得 易溶于裂解肽的细胞。 这些化合物可以用于治疗恶性或非恶性肿瘤的基因治疗，以及由具有特异性受体（如淋巴细胞）的“正常”宿主细胞的克隆或群体引起的其它疾病，因为编码溶解肽或编码溶酶体的基因 肽/肽激素融合可容易地插入到造血干细胞或骨髓前体细胞中。

公开(公告)号：US06680058B1

公开(公告)日：2004-01-20

申请号：US09486143

申请日：2000-02-22

申请人： Frederick M. Enright ,  Jesse M. Jaynes ,  William Hansel ,  Patricia A. Melrose ,  Philip H. Elzer

发明人： Frederick M. Enright ,  Jesse M. Jaynes ,  William Hansel ,  Patricia A. Melrose ,  Philip H. Elzer

IPC分类号： A61K3824

CPC分类号： C07K19/00 ,  A61K38/24 ,  C07K7/23 ,  C07K14/43563 ,  C07K14/575 ,  C07K14/59 ,  C07K2319/00 ,  Y10S514/841 ,  Y10S514/843 ,  A61K2300/00

摘要： Amphipathic lytic peptides are ideally suited to use in a ligand/cytotoxin combination to induce sterility or long-term contraception in mammals. The peptides act directly on cell membranes, and need not be internalized. Administering a combination of gonadotropin-releasing hormone (GnRH) (or a GnRH agonist) and a membrane-active lytic peptide produces long-term contraception or sterilization in mammals in vivo. The compounds are relatively small, and are not antigenic. Lysis of gonadotropes has been observed to be very rapid (on the order of ten minutes.) The two components—the ligand and the lytic peptide—may optionally be administered as a fusion peptide, or they may be administered separately, with the ligand administered slightly before the lytic peptide, to activate cells with receptors for the ligand, and thereby make those cells susceptible to lysis by the lytic peptide.

摘要翻译： 两亲性裂解肽理想地适用于配体/细胞毒素组合以诱导哺乳动物的不育或长期避孕。 肽直接作用于细胞膜上，不需要内化。 管理促性腺激素释放激素（GnRH）（或GnRH激动剂）和膜活性溶解肽的组合在哺乳动物体内产生长期避孕或灭菌。 化合物相对较小，不具抗原性。 已经观察到促性腺激素的裂解非常快（十分钟左右）。配体和裂解肽的两个组分可以任选地作为融合肽施用，或者它们可以单独给药，配体给予 在溶解肽之前稍微激活具有配体受体的细胞，从而使这些细胞易溶解裂解肽。

公开(公告)号：US06635740B1

公开(公告)日：2003-10-21

申请号：US09381879

申请日：1999-09-24

申请人： Frederick M. Enright ,  Jesse M. Jaynes ,  William Hansel ,  Kenneth L. Koonce ,  Samuel M. McCann ,  Wen H. Yu ,  Patricia A. Melrose ,  Lane D. Foil ,  Philip H. Elzer

发明人： Frederick M. Enright ,  Jesse M. Jaynes ,  William Hansel ,  Kenneth L. Koonce ,  Samuel M. McCann ,  Wen H. Yu ,  Patricia A. Melrose ,  Lane D. Foil ,  Philip H. Elzer

IPC分类号： C07K1400

CPC分类号： C12N15/8257 ,  A61K38/00 ,  C07K7/23 ,  C07K14/43563 ,  C07K14/575 ,  C07K14/59 ,  C07K19/00 ,  C07K2319/00

摘要： Amphipathic lytic peptides are ideally suited to use in a ligand/cytotoxin combination to specifically inhibit cells that are driven by or are dependent upon a specific ligand interaction; for example, to induce sterility or long-term contraception, or to attack tumor cells, or to selectively lyse virally-infected cells, or to attack lymphocytes responsible for autoimmune diseases. The peptides act directly on cell membranes, and need not be internalized. Administering a combination of gonadotropin-releasing hormone (GnRH) (or a GnRH agonist) and a membrane-active lytic peptide produces long-term contraception or sterilization in animals in vivo. Administering in vivo a combination of a ligand and a membrane-active lytic peptide kills cells with a receptor for the ligand. The compounds are relatively small, and are not antigenic. Lysis of gonadotropes has been observed to be very rapid (on the order of ten minutes.) Lysis of tumor cells is rapid. The two components—the ligand and the lytic peptide—may optionally be administered as a fusion peptide, or they may be administered separately, with the ligand administered slightly before the lytic peptide, to activate cells with receptors for the ligand, and thereby make those cells susceptible to lysis by the lytic peptide. The compounds may be used in gene therapy to treat malignant or non-malignant tumors, and other diseases caused by clones or populations of “normal” host cells bearing specific receptors (such as lymphocytes), because genes encoding a lytic peptide or encoding a lytic peptide/peptide hormone fusion may readily be inserted into hematopoietic stem cells or myeloid precursor cells.

摘要翻译： 两亲性溶解肽理想地适用于配体/细胞毒素组合以特异性抑制由特定配体相互作用驱动或依赖于特定配体相互作用的细胞; 例如，诱导不育或长期避孕，或攻击肿瘤细胞，或选择性裂解病毒感染的细胞，或攻击负责自身免疫性疾病的淋巴细胞。 肽直接作用于细胞膜上，不需要内化。 管理促性腺激素释放激素（GnRH）（或GnRH激动剂）和膜活性溶解肽的组合在体内产生长期的动物避孕或灭菌。 在体内施用配体和膜活性裂解肽的组合将细胞与配体的受体杀死。 化合物相对较小，不具抗原性。 已经观察到促性腺激素的裂解非常快（十分钟左右）。肿瘤细胞裂解很快。 两种组分 - 配体和溶解肽 - 可以任选地作为融合肽施用，或者它们可以分开施用，配体在裂解肽之前略微施用，以激活具有配体受体的细胞，从而使得 易溶于裂解肽的细胞。 这些化合物可以用于治疗恶性或非恶性肿瘤的基因治疗，以及由具有特异性受体（如淋巴细胞）的“正常”宿主细胞的克隆或群体引起的其它疾病，因为编码溶解肽或编码溶酶体的基因 肽/肽激素融合可容易地插入到造血干细胞或骨髓前体细胞中。