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    USE OF MULLERIAN INHIBITING SUBSTANCE (MIS) PROTEINS FOR CONTRACEPTION AND OVARIAN RESERVE PRESERVATION
    2.
    发明申请
    USE OF MULLERIAN INHIBITING SUBSTANCE (MIS) PROTEINS FOR CONTRACEPTION AND OVARIAN RESERVE PRESERVATION 审中-公开

    公开(公告)号：US20200376082A1

    公开(公告)日：2020-12-03

    申请号：US16988248

    申请日：2020-08-07

    Applicant: THE GENERAL HOSPITAL CORPORATION

    Inventor： Patricia K. DONAHOE ,  David PEPIN

    IPC: A61K38/22 ,  A61K38/17 ,  A61K9/00 ,  C12N7/00

    Abstract: One aspect of the invention provides a method of contraception by administering to a female subject a composition comprising Mullerian inhibiting substance (MIS). The MIS can be produced endogenously in the subject by a vector, where the vector comprises a polynucletide encoding a recombinant MIS protein. In some embodiments, the contraception is permanent and only requires administration of the composition once. Another aspect of the invention relates to a method of preserving an ovarian reserve, the method comprising administering to a female subject a composition comprising MIS or an inducible vector that comprises a polynucleotide encoding a recombinant MIS protein.

    N-METHYL PYRAZOLOANTHRONE FOR TREATMENT OF CANCER
    4.
    发明申请
    N-METHYL PYRAZOLOANTHRONE FOR TREATMENT OF CANCER 审中-公开
    N-甲基吡唑啉酮治疗癌症

    公开(公告)号：US20160250190A1

    公开(公告)日：2016-09-01

    申请号：US15029402

    申请日：2014-10-17

    Applicant: THE GENERAL HOSPITAL CORPORATION

    Inventor： David PEPIN ,  Patricia K. DONAHOE

    IPC: A61K31/4184 ,  A61K33/24 ,  A61K31/704 ,  A61K45/06

    CPC classification number: A61K31/4184 ,  A61K31/416 ,  A61K31/704 ,  A61K33/24 ,  A61K45/06 ,  A61K2300/00

    Abstract: The present invention relates to a N1-methyl-pyrazoloanthrone, e.g., a N1-methyl 1,9-pyrazoloanthrone or functional derivatives or analogues thereof to inhibit at least one kinase of the CK1 family (e.g., CSNK1A1, CSNK1B, CSNK1G1, CSNK1G2, CSNK1G3, CSNK1D, CSNK1E) and/or ARK5/NUAK1 in a cell. Another aspect relates to administration of N1-methyl-pyrazoloanthrone, e.g., a N1-methyl 1,9-pyrazoloanthrone or a functional derivative thereof in a method to treat cancer, e.g., a cancer with increased expression and/or a genetic alteration in at least one member of the CK1 family and/or ARK5/NUAK. Another aspect of the present invention relates to methods to decrease the dose of a chemotherapeutic agent by administering the chemotherapeutic agent in combination with a N1-methyl-pyrazoloanthrone, e.g., a N1-methyl 1,9-pyrazoloanthrone or a functional derivative or analogue thereof.

    Abstract translation: 本发明涉及一种N1-甲基 - 吡唑烷酮，例如N1-甲基-1,9-吡唑并丹酮或其功能衍生物或其类似物以抑制CK1家族的至少一种激酶（例如，CSNK1A1，CSNK1B，CSNK1G1，CSNK1G2， CSNK1G3，CSNK1D，CSNK1E）和/或ARK5 / NUAK1。 另一方面涉及在治疗癌症的方法中施用N1-甲基吡唑并丹酮，例如，N1-甲基-1,9-吡唑烷酮或其功能衍生物，例如，具有增加的表达和/或遗传改变的癌症 CK1系列和/或ARK5 / NUAK中的至少一名成员。 本发明的另一方面涉及通过将化学治疗剂与N1-甲基吡唑烷酮（例如，N1-甲基-1,9-吡唑并丹酮或其功能衍生物或类似物）组合施用来降低化学治疗剂的剂量的方法 。

    USE OF MULLERIAN INHIBITING SUBSTANCE (MIS) PROTEINS FOR CONTRACEPTION AND OVARIAN RESERVE PRESERVATION
    9.
    发明申请
    USE OF MULLERIAN INHIBITING SUBSTANCE (MIS) PROTEINS FOR CONTRACEPTION AND OVARIAN RESERVE PRESERVATION 审中-公开
    使用MULLERIAN抑制物质（MIS）蛋白质进行收缩和OVARIAN RESERVE保存

    公开(公告)号：US20160310574A1

    公开(公告)日：2016-10-27

    申请号：US15103568

    申请日：2014-12-11

    Applicant: THE GENERAL HOSPITAL CORPORATION

    Inventor： Patricia K. DONAHOE ,  David PEPIN

    IPC: A61K38/22 ,  A61K9/00 ,  C12N7/00

    CPC classification number: A61K38/22 ,  A61K9/0019 ,  A61K38/17 ,  C12N7/00 ,  C12N2750/14142 ,  C12N2750/14171

    Abstract: One aspect of the invention provides a method of contraception by administering to a female subject a composition comprising Mullerian inhibiting substance (MIS). The MIS can be produced endogenously in the subject by a vector, where the vector for comprises a polynucletide encoding a recombinant MIS protein. In some embodiments, the contraception is permanent and only requires administration of the composition once. Another aspect of the invention relates to a method of preserving an ovarian reserve, the method comprising administering to a female subject a composition comprising MIS or an inducible vector that comprises a polynucleotide encoding a recombinant MIS protein.

    Abstract translation: 本发明的一个方面提供了一种通过向女性受试者施用包含穆勒抑制物质（MIS）的组合物来避孕的方法。 MIS可以通过载体在受试者内部产生，其中载体包含编码重组MIS蛋白的多核苷酸。 在一些实施方案中，避孕是永久性的，并且仅需要施用组合物一次。 本发明的另一方面涉及一种保存卵巢储备的方法，所述方法包括向雌性受试者施用包含MIS或包含编码重组MIS蛋白的多核苷酸的可诱导载体的组合物。

    MODIFIED MULLERIAN INHIBITING SUBSTANCE (MIS) PROTEINS AND USES THEREOF FOR THE TREATMENT OF DISEASES
    10.
    发明申请
    MODIFIED MULLERIAN INHIBITING SUBSTANCE (MIS) PROTEINS AND USES THEREOF FOR THE TREATMENT OF DISEASES 审中-公开
    改良的MOLERIAN抑制物质（MIS）蛋白及其用于治疗疾病的用途

    公开(公告)号：US20160039898A1

    公开(公告)日：2016-02-11

    申请号：US14773936

    申请日：2014-03-12

    Applicant: THE GENERAL HOSPITAL CORPORATION ,  MASSACHUSETTS EYE AND EAR INFIRMARY

    Inventor： Patricia K. DONAHOE ,  Demetrios VAVVAS ,  David PEPIN ,  Mien Van HOANG

    IPC: C07K14/575

    CPC classification number: C07K14/575 ,  A61K31/416 ,  A61K38/00 ,  A61K45/06 ,  C07K14/765 ,  C07K2319/43 ,  C07K2319/50 ,  Y02A50/473 ,  A61K2300/00

    Abstract: The present invention relates to modified recombinant human MIS protein which has improved cleavage and increased bioactivity and increased potency as compared to wild-type human MIS protein. Other aspects of the invention relate to methods to prevent and treat cancers, such as cancers that express the MIS receptor type II (MISRII) by administering to a subject a composition comprising a recombinant human MIS protein. Another aspect of the present invention relates to methods to lower plasma androgen levels in a subject, and/or for the treatment of a subject with a disease characterized by excess androgen. Another aspect provides pharmaceutical compositions and kits and methods for use comprising a recombinant human MIS protein. Another aspect of the present invention relates to methods to decrease the dose of a chemotherapeutic agent by administering the chemotherapeutic agent with the recombinant MIS protein that lowers the effective dose of the chemotherapeutic agent.

    Abstract translation: 本发明涉及与野生型人MIS蛋白相比具有改进的切割和增加的生物活性和增加的效力的修饰的重组人MIS蛋白。 本发明的其它方面涉及通过向受试者施用包含重组人MIS蛋白的组合物来预防和治疗癌症，例如表达MIS受体II型（MISRII）的癌症的方法。 本发明的另一方面涉及降低受试者血浆雄激素水平和/或治疗以过量雄激素为特征的疾病的受试者的方法。 另一方面提供了包含重组人MIS蛋白的药物组合物和用于使用的试剂盒和方法。 本发明的另一方面涉及通过使化学治疗剂与降低化学治疗剂的有效剂量的重组MIS蛋白质来降低化学治疗剂的剂量的方法。

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