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公开(公告)号：US20200338094A1
公开(公告)日：2020-10-29
申请号：US16893012
申请日：2020-06-04
IPC分类号： A61K31/635 , A61K31/496 , A61K31/675 , A61K9/00 , A61K9/12 , A61K8/00
摘要： A library of heterocyclic compounds has been screened to identify particular compounds that have high inhibitory capacity for the Bcl family of regulatory proteins. Compounds identified as Bcl antagonists have been further screened to select pharmaceutical agents with both high potency and high specificity for eliminating senescent cells in comparison with replicative or quiescent cells of the same tissue type. Particular structures are identified in this disclosure that eliminate senescent cells with an EC50 in the nanomole range and a specificity around or above 100-fold. In accordance with this invention, heterocyclic compounds provided in this disclosure can be formulated for the treatment of a range of age-related conditions caused or mediated by senescent cells. Such conditions are exemplified by ophthalmic conditions, pulmonary conditions, and osteoarthritis.
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公开(公告)号：US10328073B2
公开(公告)日：2019-06-25
申请号：US16054667
申请日：2018-08-03
申请人： Unity Biotechnology, Inc. , Buck Institute for Research on Aging , Mayo Foundation for Medical Education and Research
发明人： Remi-Martin Laberge , Judith Campisi , Marco Demaria , Nathaniel David , Alain Philippe Vasserot , James L. Kirkland , Tamar Tchkonia , Yi Zhu , Darren J. Baker , Bennett G. Childs , Jan M. A. van Deursen
IPC分类号： A61K31/496 , A61P27/02 , A61P11/00 , A61P9/10 , A61K31/428 , A61K31/495 , A61K31/5377 , A61K31/404 , A61K31/4375 , A61K45/06 , A61K31/4178 , A61K31/728 , C12N5/00 , A61K47/36 , A61K9/00
摘要： Methods are provided herein for selectively killing senescent cells and for treating senescence-associated diseases and disorders by administering a senolytic agent. Senescence-associated diseases and disorders treatable by the methods using the senolytic agents described herein include cardiovascular diseases and disorders associated with or caused by arteriosclerosis, such as atherosclerosis; idiopathic pulmonary fibrosis; chronic obstructive pulmonary disease; osteoarthritis; senescence-associated ophthalmic diseases and disorders; and senescence-associated dermatological diseases and disorders.
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3.发明授权公开(公告)号：US10328058B2
公开(公告)日：2019-06-25
申请号：US15792593
申请日：2017-10-24
申请人： Mayo Foundation for Medical Education and Research , Unity Biotechnology, Inc. , Buck Institute for Research on Aging
发明人： Darren J. Baker , Marco Demaria , Albert Davalos , Bennett G. Childs , Jan M. A. van Deursen , James L. Kirkland , Tamar Tchkonia , Yi Zhu , Nathaniel David , Remi-Martin Laberge , Judith Campisi
IPC分类号： A61P9/10 , A61K31/496 , A61K31/4178 , A61K31/404 , A61K31/428 , A61K31/4375 , A61K31/5377 , A61K9/00 , A61K31/4164 , A61K45/06 , A61K47/36 , C12N5/00
摘要： Foamy macrophages with senescence markers accumulate in the subendothelial space at the onset of atherosclerosis where they drive pathology by increasing expression of key atherogenic and inflammatory cytokines and chemokines. In advanced lesions, senescent cells promote features of plaque instability, including elastic fiber degradation and fibrous cap thinning, by heightening metalloprotease production. This invention provides methods and materials for treating arthritis by removing senescent cells in or around atherosclerotic plaques, thereby stabilizing the plaques, inhibiting rupture of the plaques and pathological sequelae that manifest as coronary artery disease.
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公开(公告)号：US10258618B2
公开(公告)日：2019-04-16
申请号：US15955542
申请日：2018-04-17
申请人： Buck Institute for Research on Aging , Unity Biotechnology, Inc. , Mayo Foundation for Medical Education and Research
发明人： Remi-Martin Laberge , Judith Campisi , Marco Demaria , Nathaniel David , Darren J. Baker , James L. Kirkland , Tamar Tchkonia , Yi Zhu , Jan M. A. van Deursen
IPC分类号： A61K9/00 , A61K31/496 , A61K31/5377 , A61P11/00 , A61K31/428 , A61K31/495 , A61K31/404 , A61K31/4375 , A61K45/06 , A61K31/4178 , A61K31/728 , C12N5/00 , A61K47/36
摘要： Methods are provided herein for selectively killing senescent cells and for treating senescence-associated diseases and disorders by administering a senolytic agent. Senescence-associated diseases and disorders treatable by the methods using the senolytic agents described herein include cardiovascular diseases and disorders associated with or caused by arteriosclerosis, such as atherosclerosis; idiopathic pulmonary fibrosis; chronic obstructive pulmonary disease; osteoarthritis; senescence-associated ophthalmic diseases and disorders; and senescence-associated dermatological diseases and disorders.
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公开(公告)号：US20180256568A1
公开(公告)日：2018-09-13
申请号：US15950965
申请日：2018-04-11
申请人： Buck Institute for Research on Aging , Unity Biotechnology, Inc. , Mayo Foundation for Medical Education and Research , The Johns Hopkins University
发明人： Remi-Martin Laberge , Judith Campisi , Albert Davalos , Marco Demaria , Nathaniel David , Alain Philippe Vasserot , Darren J. Baker , Bennett G. Childs , James L. Kirkland , Tamar Tchkonia , Jan M.A. van Deursen , Jennifer Elisseeff , Chaekyu Kim , Okhee Jeon , Allyson K. Palmer , Yi Zhu
IPC分类号： A61K31/496 , A61K31/4375 , A61K31/5377 , A61K31/428 , A61K31/404 , A61K45/06
CPC分类号： A61K31/496 , A61K9/0048 , A61K9/0073 , A61K31/404 , A61K31/4178 , A61K31/428 , A61K31/4375 , A61K31/495 , A61K31/5377 , A61K31/728 , A61K45/06 , A61K47/36 , A61P9/10 , A61P11/00 , A61P27/02 , C12N5/0081 , C12N2501/999 , C12N2503/02 , C12Q1/485
摘要： Methods are provided herein for selectively killing senescent cells and for treating senescence-associated diseases and disorders by administering a senolytic agent. Senescence-associated diseases and disorders treatable by the methods using the senolytic agents described herein include cardiovascular diseases and disorders associated with or caused by arteriosclerosis, such as atherosclerosis; idiopathic pulmonary fibrosis; chronic obstructive pulmonary disease; osteoarthritis; senescence-associated ophthalmic diseases and disorders; and senescence-associated dermatological diseases and disorders.
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公开(公告)号：US09980962B2
公开(公告)日：2018-05-29
申请号：US15647688
申请日：2017-07-12
申请人： Buck Institute for Research on Aging , Unity Biotechnology, Inc. , Mayo Foundation for Medical Education and Research
发明人： Remi-Martin Laberge , Judith Campisi , Marco Demaria , Nathaniel David , Darren J. Baker , James L. Kirkland , Tamar Tchkonia , Jan M. A. van Deursen , Yi Zhu
IPC分类号： A61K31/537 , A61K31/496 , A61K31/495 , A61K31/5377 , A61K31/404 , A61K31/4375 , A61K31/428 , A61K45/06 , A61K9/00
CPC分类号： A61K31/496 , A61K9/0048 , A61K9/0073 , A61K31/404 , A61K31/4178 , A61K31/428 , A61K31/4375 , A61K31/495 , A61K31/5377 , A61K31/728 , A61K45/06 , A61K47/36 , C12N5/0081 , C12N2501/999 , C12N2503/02
摘要： Methods are provided herein for selectively killing senescent cells and for treating senescence-associated diseases and disorders by administering a senolytic agent. Senescence-associated diseases and disorders treatable by the methods using the senolytic agents described herein include cardiovascular diseases and disorders associated with or caused by arteriosclerosis, such as atherosclerosis; idiopathic pulmonary fibrosis; chronic obstructive pulmonary disease; osteoarthritis; senescence-associated ophthalmic diseases and disorders; and senescence-associated dermatological diseases and disorders.
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公开(公告)号：US09855266B2
公开(公告)日：2018-01-02
申请号：US15467129
申请日：2017-03-23
申请人： Buck Institute for Research on Aging , Unity Biotechnology, Inc. , Mayo Foundation for Medical Education and Research , The Johns Hopkins University
发明人： Remi-Martin Laberge , Judith Campisi , Albert Davalos , Marco Demaria , Nathaniel David , Alain Philippe Vasserot , James L. Kirkland , Tamar Tchkonia , Jennifer Elisseeff , Chaekyu Kim , Okhee Jeon , Yi Zhu
IPC分类号： A61K31/417 , A61K31/496 , A61K47/36 , A61K31/4178
CPC分类号： A61K31/496 , A61K9/0048 , A61K9/0073 , A61K31/404 , A61K31/4178 , A61K31/428 , A61K31/4375 , A61K31/495 , A61K31/5377 , A61K31/728 , A61K45/06 , A61K47/36 , C12N5/0081 , C12N2501/999 , C12N2503/02
摘要： Methods are provided herein for selectively killing senescent cells and for treating senescence-associated diseases and disorders by administering a senolytic agent. Senescence-associated diseases and disorders treatable by the methods using the senolytic agents described herein include cardiovascular diseases and disorders associated with or caused by arteriosclerosis, such as atherosclerosis; idiopathic pulmonary fibrosis; chronic obstructive pulmonary disease; osteoarthritis; senescence-associated ophthalmic diseases and disorders; and senescence-associated dermatological diseases and disorders.
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公开(公告)号：US20170348307A1
公开(公告)日：2017-12-07
申请号：US15647688
申请日：2017-07-12
申请人： Buck Institute for Research on Aging , Unity Biotechnology, Inc. , Mayo Foundation for Medical Education and Research , The Johns Hopkins University
发明人： Remi-Martin Laberge , Judith Campisi , Albert Davalos , Marco Demaria , Nathaniel David , Alain Philippe Vasserot , Darren J. Baker , Bennett G. Childs , James L. Kirkland , Tamar Tchkonia , Jan M.A. van Deursen , Jennifer Elisseeff , Chaekyu Kim , Okhee Jeon , Allyson K. Palmer
IPC分类号： A61K31/496 , A61K31/5377 , A61K31/495 , A61K31/4375 , A61K31/428 , A61K45/06 , A61K31/404
CPC分类号： A61K31/496 , A61K9/0048 , A61K9/0073 , A61K31/404 , A61K31/4178 , A61K31/428 , A61K31/4375 , A61K31/495 , A61K31/5377 , A61K31/728 , A61K45/06 , A61K47/36 , C12N5/0081 , C12N2501/999 , C12N2503/02
摘要： Methods are provided herein for selectively killing senescent cells and for treating senescence-associated diseases and disorders by administering a senolytic agent. Senescence-associated diseases and disorders treatable by the methods using the senolytic agents described herein include cardiovascular diseases and disorders associated with or caused by arteriosclerosis, such as atherosclerosis; idiopathic pulmonary fibrosis; chronic obstructive pulmonary disease; osteoarthritis; senescence-associated ophthalmic diseases and disorders; and senescence-associated dermatological diseases and disorders.
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公开(公告)号：US11963957B2
公开(公告)日：2024-04-23
申请号：US17114376
申请日：2020-12-07
申请人： Buck Institute for Research on Aging , Unity Biotechnology, Inc. , Mayo Foundation for Medical Education and Research
发明人： Remi-Martin Laberge , Judith Campisi , Albert Davalos , Marco Demaria , Nathaniel David , Jan M. A. van Deursen , Darren J. Baker , Bennett G. Childs
IPC分类号： A61P9/10 , A61K9/00 , A61K31/404 , A61K31/4178 , A61K31/428 , A61K31/4375 , A61K31/495 , A61K31/496 , A61K31/5377 , A61K31/728 , A61K45/06 , A61K47/36 , A61K47/68 , A61P11/00 , A61P25/28 , A61P27/02 , C12N5/00 , C12N15/113 , C12Q1/48
CPC分类号： A61K31/496 , A61K9/0048 , A61K9/0073 , A61K31/404 , A61K31/4178 , A61K31/428 , A61K31/4375 , A61K31/495 , A61K31/5377 , A61K31/728 , A61K45/06 , A61K47/36 , A61K47/6807 , A61P9/10 , A61P11/00 , A61P25/28 , A61P27/02 , C12N5/0081 , C12N15/113 , C12N2320/30 , C12N2501/999 , C12N2503/02 , C12Q1/485
摘要： Methods are provided herein for selectively killing senescent cells and for treating senescence-associated diseases and disorders by administering a senolytic agent. Senescence-associated diseases and disorders treatable by the methods using the senolytic agents described herein include cardiovascular diseases and disorders associated with or caused by arteriosclerosis, such as atherosclerosis; idiopathic pulmonary fibrosis; chronic obstructive pulmonary disease; osteoarthritis; senescence-associated ophthalmic diseases and disorders; and senescence-associated dermatological diseases and disorders.
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公开(公告)号：US11351167B2
公开(公告)日：2022-06-07
申请号：US16584638
申请日：2019-09-26
申请人： Buck Institute for Research on Aging , Mayo Foundation for Medical Education and Research , Unity Biotechnology, Inc.
发明人： Remi-Martin Laberge , Judith Campisi , Marco Demaria , Nathaniel David , James L. Kirkland , Tamar Tchkonia , Yi Zhu , Darren J. Baker , Jan M. A. van Deursen
IPC分类号： A61K31/496 , A61P11/00 , A61P9/10 , A61P27/02 , A61K31/428 , A61K31/495 , A61K31/5377 , C12N15/113 , A61P25/28 , A61K47/68 , A61K31/404 , A61K31/4375 , A61K45/06 , A61K31/4178 , A61K31/728 , C12N5/00 , A61K47/36 , A61K9/00 , C12Q1/48
摘要： Methods are provided herein for selectively killing senescent cells and for treating senescence-associated diseases and disorders by administering a senolytic agent. Senescence-associated diseases and disorders treatable by the methods using the senolytic agents described herein include cardiovascular diseases and disorders associated with or caused by arteriosclerosis, such as atherosclerosis; idiopathic pulmonary fibrosis; chronic obstructive pulmonary disease; osteoarthritis; senescence-associated ophthalmic diseases and disorders; and senescence-associated dermatological diseases and disorders.
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