公开(公告)号：US11351167B2

公开(公告)日：2022-06-07

申请号：US16584638

申请日：2019-09-26

Applicant: Buck Institute for Research on Aging ,  Mayo Foundation for Medical Education and Research ,  Unity Biotechnology, Inc.

Inventor： 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: 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

Abstract: 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.

公开(公告)号：US20220096466A1

公开(公告)日：2022-03-31

申请号：US17548004

申请日：2021-12-10

Applicant: Buck Institute for Research and Aging ,  Unity Biotechnology, Inc.

Inventor： Shankar J. Chinta ,  Judith Campisi ,  Julie K. Andersen ,  Remi-Martin Laberge ,  Nathaniel David

IPC: A61K31/496 ,  A61P9/10 ,  A61K47/36 ,  A61K9/00 ,  A61P11/00 ,  A61P27/02 ,  C12N5/00 ,  A61K31/728 ,  A61K31/4178 ,  A61K45/06 ,  A61K31/4375 ,  A61K31/404 ,  A61K31/5377 ,  A61K31/495 ,  A61K31/428 ,  A61P25/16

Abstract: This invention establishes a new paradigm for treatment of Parkinson's disease (PD) by eliminating senescent cells that reside in or around the site of the disease pathophysiology. Exposure of test subjects to the herbicide paraquat (PQ) increases the risk for developing Parkinson's disease. The data in this disclosure show that PQ induces a senescence arrest and SASP in astrocytes, in culture and in vivo in mice, and senescent cell markers were present in astrocytes in midbrain tissue from PD patients. In a transgenic mouse model, senescent cell ablation protected against PQ-induced PD-like neuropathology. Removal of senescent cells from affected sites using small molecule agents that specifically target senescent cells can help prevent or ameliorate signs and symptoms of the disease.

公开(公告)号：US20190175623A1

公开(公告)日：2019-06-13

申请号：US16181163

申请日：2018-11-05

Applicant: Buck Institute for Research on Aging ,  Unity Biotechnology, Inc.

Inventor： Remi-Martin Laberge ,  Nathaniel David

IPC: A61K31/635 ,  A61K9/00 ,  A61K8/00 ,  A61K31/496 ,  A61K31/675 ,  A61K9/12

Abstract: 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 nanomolar 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.

公开(公告)号：US20180235957A1

公开(公告)日：2018-08-23

申请号：US15956613

申请日：2018-04-18

Applicant: Buck Institute for Research on Aging ,  Mayo Foundation for Medical Education and Research ,  Unity Biotechnology, Inc.

Inventor： 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: A61K31/496 ,  A61K31/4178 ,  A61K9/00 ,  A61K31/728

Abstract: 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.

公开(公告)号：US09993472B2

公开(公告)日：2018-06-12

申请号：US15114762

申请日：2015-01-28

Applicant: Buck Institute for Research on Aging ,  Unity Biotechnology, Inc. ,  Mayo Foundation for Medical Education and Research ,  The Johns Hopkins University

Inventor： Remi-Martin Laberge ,  Judith Campisi ,  Albert Davalos ,  Marco Demaria ,  Nathaniel David ,  Alain Philippe Vasserot ,  James L. Kirkland ,  Tamar Tchkonia ,  Jan M. A. van Deursen ,  Jennifer Elisseeff ,  Chaekyu Kim ,  Okhee Jeon ,  Yi Zhu

IPC: A61K31/496 ,  A61K31/4375 ,  A61K31/5377 ,  A61K31/428 ,  A61K31/404 ,  A61K45/06

CPC classification number: 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

Abstract: 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.

公开(公告)号：US20180110787A1

公开(公告)日：2018-04-26

申请号：US15808417

申请日：2017-11-09

Applicant: Buck Institute for Research on Aging ,  Unity Biotechnology, Inc.

Inventor： Remi-Martin Laberge ,  Nathaniel David

IPC: A61K31/635 ,  A61K9/12 ,  A61K9/00

CPC classification number: A61K31/635 ,  A61K8/00 ,  A61K9/0019 ,  A61K9/0048 ,  A61K9/0073 ,  A61K9/12 ,  A61K31/496 ,  A61K31/675

Abstract: 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.

公开(公告)号：US20170326136A1

公开(公告)日：2017-11-16

申请号：US15481129

申请日：2017-04-06

Applicant: Unity Biotechnology, Inc. ,  Buck Institute for Research on Aging ,  The Johns Hopkins University

Inventor： Nathaniel David ,  Albert Davalos ,  Remi-Martin Laberge ,  Judith Campisi ,  Marco Demaria ,  Alain Vasserot ,  Chaekyu Kim ,  Okhee Jeon ,  Jennifer Elisseeff

IPC: A61K31/496 ,  A61K47/36

CPC classification number: 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

Abstract: This disclosure provides a technology for managing the sensation of pain in a subject in need thereof. Treatment methods according to this invention include administering to the subject a formulation that contains an effective amount of (4-[(4S,5R)-4,5-bis(4-chlorophenyl)-4,5-dihydro-2-[4-methoxy-2-(1-methylethoxy)phenyl]-1H-imidazol-1-yl]carbonyl]-2-piperazinone).

公开(公告)号：US20170266211A1

公开(公告)日：2017-09-21

申请号：US15611589

申请日：2017-06-01

Applicant: Unity Biotechnology, Inc. ,  Buck Institute for Research on Aging

Inventor： Nathaniel David ,  Remi-Martin Laberge

IPC: A61K31/675

CPC classification number: A61K31/675

Abstract: Disclosed herein are compounds that are effective for treatment of various disease states. Dosing includes both single administration and regimens of cycling dosages.

公开(公告)号：US20170209435A1

公开(公告)日：2017-07-27

申请号：US15467129

申请日：2017-03-23

Applicant: Buck Institute for Research on Aging ,  Unity Biotechnology, Inc. ,  Mayo Foundation for Medical Education and Research ,  The John Hopkins University

Inventor： 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: A61K31/496 ,  A61K47/36

CPC classification number: 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

Abstract: 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.

公开(公告)号：US20240245680A1

公开(公告)日：2024-07-25

申请号：US18289554

申请日：2022-05-25

Applicant: Scott KIMURA ,  Unity Biotechnology, Inc.

Inventor： Remi-Martin Laberge ,  Scott Kimura ,  Przemyslaw Sapieha ,  Pamela Tsuruda ,  Pieter Bas-Kwak ,  Nathan Gushwa ,  Tianna Chow

IPC: A61K31/497 ,  A61K31/4152 ,  A61K31/437 ,  A61K45/06 ,  A61P27/02

CPC classification number: A61K31/497 ,  A61K31/4152 ,  A61K31/437 ,  A61K45/06 ,  A61P27/02

Abstract: The invention relates to methods of treating certain retinal vasculopathies such as diabetic macular edema, diabetic retinopathy and dry and neovascular age-related macular degeneration, among others. In some instances, the method includes treating a patient suffering from a retinal vasculopathy by administering an agent to the patient. The agent can be one or more of the agents as described herein.