公开(公告)号：US10655144B2

公开(公告)日：2020-05-19

申请号：US15870172

申请日：2018-01-12

申请人： Buck Institute for Research on Aging

发明人： Marco Demaria ,  Francis Rodier ,  Remi-Martin Laberge ,  Judith Campisi

IPC分类号： C12N15/85 ,  A01K67/027 ,  A61K49/00

摘要： This disclosure provides non-human animal models for age-related disorders and age-sensitive traits, particularly those caused by senescence-inducing stimuli, wherein the models comprise transgenes selectively expressed by senescent cells. The disclosure further provides methods for identifying therapeutic agents effective for treating or preventing age-related disorders and age-sensitive traits using the animal models, therapeutic agents identified using such methods, pharmaceutical compositions comprising the identified therapeutic agents, and methods of treating or preventing age-related disorders and age-sensitive traits.

公开(公告)号：US09901081B2

公开(公告)日：2018-02-27

申请号：US15080991

申请日：2016-03-25

申请人： Buck Institute for Research on Aging ,  Erasmus University Medical Center Rotterdam ,  James Mitchell ,  Wendy Toussaint

发明人： Judith Campisi ,  Marco Demaria ,  Francis Rodier ,  Remi-Martin Laberge ,  James Mitchell ,  Jan H. J. Hoeijmakers ,  Wendy Toussaint

IPC分类号： A01K67/027 ,  A61K49/00 ,  C12N15/85 ,  C12N9/50 ,  G01N33/50

CPC分类号： A01K67/0275 ,  A01K2217/206 ,  A01K2227/105 ,  A01K2267/0331 ,  A01K2267/0393 ,  A61K49/0008 ,  C07K2319/60 ,  C07K2319/61 ,  C07K2319/70 ,  C12N9/1211 ,  C12N9/50 ,  C12N9/6475 ,  C12N9/90 ,  C12N15/8509 ,  C12N2015/8572 ,  G01N33/5011 ,  G01N33/5088

摘要： This invention provides a transgenic mouse with a p16INK4a promoter sequence that controls expression of a protein such that it is expressed preferentially in senescent cells. The protein either directly induces apoptosis, or converts a prodrug to a cytotoxic compound. In addition, the mouse is injected with syngeneic tumor cells, or has second transgene that causes tumors to form. Removing senescent cells from the mouse may result in the formation of fewer tumors.

公开(公告)号：US20140335074A1

公开(公告)日：2014-11-13

申请号：US14365040

申请日：2012-12-13

申请人： Buck Institute for Research on Aging

发明人： Judith Campisi ,  Marco Demaria

IPC分类号： A61K31/522 ,  A61K31/4545 ,  G01N33/50 ,  A61K39/21 ,  A61K38/28 ,  A61K38/08 ,  A61N5/10 ,  A61K45/06

CPC分类号： A61K31/573 ,  A01K67/0275 ,  A01K2217/052 ,  A01K2217/30 ,  A01K2227/105 ,  A01K2267/0331 ,  A01K2267/0393 ,  A61K31/352 ,  A61K31/4545 ,  A61K31/522 ,  A61K38/085 ,  A61K38/28 ,  A61K39/21 ,  A61K45/06 ,  A61N5/10 ,  A61N2005/1089 ,  G01N33/5011 ,  G01N33/502 ,  G01N33/5023 ,  G01N33/5044 ,  G01N2500/10

摘要： Methods are provided herein for enhancing the effectiveness of medical therapies by administering agents that suppress a biological damage response that is inducible by the medical therapy administered to a subject. In certain embodiments, a method is provided for administering an anti-senescent cell agent that suppresses a biological response comprising cellular senescence that is induced by the medical therapy.

摘要翻译： 本文提供了通过施用抑制由施用于受试者的药物治疗可诱导的生物损伤反应的施用试剂来提高药物疗法的有效性的方法。 在某些实施方案中，提供了一种施用抑制由药物治疗诱导的包含细胞衰老的生物反应的抗衰老细胞剂的方法。

公开(公告)号：US09901080B2

公开(公告)日：2018-02-27

申请号：US15067543

申请日：2016-03-11

申请人： Buck Institute for Research on Aging ,  Erasmus University Medical Center Rotterdam ,  James Mitchell ,  Wendy Toussaint

发明人： Judith Campisi ,  Marco Demaria ,  Remi-Martin Laberge ,  Francis Rodier ,  James Mitchell ,  Jan H. J. Hoeijmakers ,  Wendy Toussaint

IPC分类号： A01K67/027 ,  A61K49/00 ,  C12N15/85

CPC分类号： A01K67/0275 ,  A01K2217/052 ,  A01K2227/105 ,  A01K2267/0393 ,  A61K49/0008 ,  C12N15/8509 ,  C12N2015/859 ,  C12N2830/008

摘要： This invention provides a transgenic mouse for studying the role of senescent cells on an age-related disorder or an age-sensitive trait. The transgene contains a p16 promoter sequence that controls expression of an enzyme so as to cause the enzyme to be expressed in senescent cells in the mouse. The enzyme converts a prodrug to a cytotoxic agent, so that treating the mouse with the prodrug results in the prodrug selectively killing the senescent cells. As a result, progression of an age-related disorder or an age-sensitive trait is delayed. Included is the 3MR mouse model, which also expresses bioluminescent and fluorescent markers under control of the p16 promoter so that senescent cells in the mice can be visualized.

公开(公告)号：US20170119789A1

公开(公告)日：2017-05-04

申请号：US15077630

申请日：2016-03-22

申请人： Buck Institute for Research on Aging

发明人： Judith Campisi ,  Marco Demaria

IPC分类号： A61K31/573 ,  A61K45/06 ,  G01N33/50 ,  A61K31/352

CPC分类号： A61K31/573 ,  A01K67/0275 ,  A01K2217/052 ,  A01K2217/30 ,  A01K2227/105 ,  A01K2267/0331 ,  A01K2267/0393 ,  A61K31/352 ,  A61K31/4545 ,  A61K31/522 ,  A61K38/085 ,  A61K38/28 ,  A61K39/21 ,  A61K45/06 ,  A61N5/10 ,  A61N2005/1089 ,  G01N33/5011 ,  G01N33/502 ,  G01N33/5023 ,  G01N33/5044 ,  G01N2500/10

摘要： Methods are provided herein for enhancing the effectiveness of medical therapies by administering agents that suppress a biological damage response that is inducible by the medical therapy administered to a subject. In certain embodiments, a method is provided for administering an anti-senescent cell agent that suppresses a biological response comprising cellular senescence that is induced by the medical therapy.