公开(公告)号：US06379925B1

公开(公告)日：2002-04-30

申请号：US09467997

申请日：1999-12-20

Applicant: Jan Kitajewski ,  Hendrik Uyttendaele

Inventor： Jan Kitajewski ,  Hendrik Uyttendaele

IPC: C12P2102

CPC classification number: G01N33/5011 ,  A61K38/00 ,  C07K14/705 ,  C07K16/28 ,  C07K2317/34 ,  G01N33/5008 ,  G01N33/5026 ,  G01N33/5064 ,  G01N33/68 ,  G01N2333/705

Abstract: This invention provides methods of modulating angiogenesis, including promoting or inhibiting angiogenesis, e.g., in connection with treating abnormalities including hemangiomas, hemangiosarcomas, Kaposi's Sarcoma, ischemic disorders, and wounds. These methods involve administration of compounds that are selective agonists or antagonists of Notch4 protein. In addition, this invention provides an isolated nucleic acid molecule encoding a Notch4, an isolated Notch4 protein, vectors comprising an isolated nucleic acid molecule encoding a Notch4 protein, cells comprising such vectors, antibodies directed to Notch4 protein, nucleic acid probes useful for detecting nucleic acids encoding Notch4 protein, and antisense oligonucleotides complementary to any unique sequences of a nucleic acid molecule which encodes Notch4 protein.

Abstract translation: 本发明提供调节血管生成的方法，包括促进或抑制血管生成，例如与治疗异常，包括血管瘤，血管肉瘤，卡波西肉瘤，缺血性疾病和伤口有关。 这些方法涉及施用作为Notch4蛋白质的选择性激动剂或拮抗剂的化合物。 此外，本发明提供了编码Notch4，分离的Notch4蛋白的分离的核酸分子，包含编码Notch4蛋白的分离的核酸分子的载体，包含此类载体的细胞，针对Notch4蛋白的抗体，用于检测核酸的核酸探针 编码Notch4蛋白的酸和与编码Notch4蛋白的核酸分子的任何独特序列互补的反义寡核苷酸。

公开(公告)号：US20160115217A1

公开(公告)日：2016-04-28

申请号：US14844642

申请日：2015-09-03

Applicant: Jan Kitajewski ,  Carrie Shawber

Inventor： Jan Kitajewski ,  Carrie Shawber

IPC: C07K14/705

CPC classification number: C07K14/705 ,  A61K38/00 ,  C07K2319/02 ,  C07K2319/30

Abstract: This invention provides a fusion protein comprising a signal peptide, an extracellular domain of human Notch receptor protein and an Fc portion of an antibody bound thereto. This invention also provides a method for treating a subject having a tumor, a method for inhibiting angiogenesis in a subject, a method for treating a subject having ovarian cancer, and a method for treating a subject having a metabolic disorder, comprising administering to the subject an amount of the above fusion protein effective to treat the subject. This invention further provides uses of the above fusion protein for the preparation of a pharmaceutical composition for the treatment of a subject having a tumor, for inhibiting angiogenesis in a subject, for treating a subject having ovarian cancer, and for treating a subject having a metabolic disorder.

Abstract translation: 本发明提供了包含信号肽，人Notch受体蛋白质的细胞外结构域和与其结合的抗体的Fc部分的融合蛋白质。 本发明还提供了治疗患有肿瘤的受试者的方法，用于抑制受试者血管发生的方法，用于治疗患有卵巢癌的受试者的方法，以及用于治疗具有代谢紊乱的受试者的方法，所述方法包括对所述受试者施用 上述融合蛋白有效治疗受试者的量。 本发明还提供了上述融合蛋白用于制备用于治疗患有肿瘤的受试者，用于抑制受试者的血管生成，用于治疗患有卵巢癌的受试者的药物组合物的用途，以及用于治疗具有代谢 紊乱。

公开(公告)号：US20150329615A1

公开(公告)日：2015-11-19

申请号：US14668525

申请日：2015-03-25

Applicant: Jan Kitajewski ,  Carrie Shawber ,  Yasuhiro Funahashi

Inventor： Jan Kitajewski ,  Carrie Shawber ,  Yasuhiro Funahashi

IPC: C07K14/705

CPC classification number: A61K48/00 ,  A61K9/0019 ,  A61K38/00 ,  C07K14/705 ,  C07K2319/30 ,  C07K2319/32

Abstract: This invention provides a method for treating a subject having a tumor and a method for inhibiting angiogenesis in a subject, both comprising administering to the subject an effective amount of a composition of matter comprising the extracellular domain of a Notch receptor protein operably affixed to a half-life-increasing moiety. This invention also provides a composition of matter comprising the extracellular domain of Notch4 receptor protein operably affixed to a half-life-increasing moiety. This invention further provides an article of manufacture. Finally, this invention provides a replicable vector which encodes a polypeptide comprising the extracellular domain of a Notch receptor protein operably affixed to a half-life-increasing moiety, a host vector system which comprises such replicable vector and a method of producing such polypeptide.

Abstract translation: 本发明提供了治疗患有肿瘤的受试者的方法和用于抑制受试者血管生成的方法，所述方法包括向受试者施用有效量的包含Notch受体蛋白的细胞外结构域的物质组合物， 生命增加部分。 本发明还提供了包含Notch4受体蛋白的细胞外结构域的物质组合物，其可操作地附着于半衰期增加的部分。 本发明还提供了一种制造品。 最后，本发明提供了可复制载体，其编码包含可操作地附着于半衰期增加部分的Notch受体蛋白的细胞外结构域的多肽，包含该可复制载体的宿主载体系统和产生该多肽的方法。

公开(公告)号：US09127085B2

公开(公告)日：2015-09-08

申请号：US12733329

申请日：2008-08-22

Applicant: Jan Kitajewski ,  Carrie Shawber

Inventor： Jan Kitajewski ,  Carrie Shawber

IPC: C07K14/705 ,  A61K38/00

CPC classification number: C07K14/705 ,  A61K38/00 ,  C07K2319/02 ,  C07K2319/30

Abstract: This invention provides a fusion protein comprising a single peptide, an extracellular domain of human Notch receptor protein and an Fc portion of an antibody bound thereto. This invention also provides a method for treating a subject having a tumor, a method for inhibiting angiogenesis in a subject, a method for treating a subject having ovarian cancer, and a method for treating a subject having a metabolic disorder, comprising administering to the subject an amount of the above fusion protein effective to treat the subject. This invention further provides uses of the above fusion protein for the preparation of a pharmaceutical composition for the treatment of a subject having a tumor, for inhibiting angiogenesis in a subject, for treating a subject having ovarian cancer, and for treating a subject having a metabolic disorder.

Abstract translation: 本发明提供了包含单个肽，人类Notch受体蛋白质的细胞外结构域和与之结合的抗体的Fc部分的融合蛋白质。 本发明还提供了治疗患有肿瘤的受试者的方法，用于抑制受试者血管发生的方法，用于治疗患有卵巢癌的受试者的方法，以及用于治疗具有代谢紊乱的受试者的方法，所述方法包括对所述受试者施用 上述融合蛋白有效治疗受试者的量。 本发明还提供了上述融合蛋白用于制备用于治疗患有肿瘤的受试者，用于抑制受试者的血管生成，用于治疗患有卵巢癌的受试者的药物组合物的用途，以及用于治疗具有代谢 紊乱。