公开(公告)号：US20200338094A1

公开(公告)日：2020-10-29

申请号：US16893012

申请日：2020-06-04

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

Inventor： Nathaniel David ,  Remi-Martin Laberge

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

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：US20200002378A1

公开(公告)日：2020-01-02

申请号：US16538557

申请日：2019-08-12

Applicant: UNITY BIOTECHNOLOGY, INC.

Inventor： Ryan Hudson ,  Anne-Marie Beausoleil ,  F. Anthony Romero ,  Remi-Martin Laberge

IPC: C07K7/06 ,  C07K5/10 ,  C07K5/06 ,  C07D303/32 ,  A61P35/00 ,  C07K5/08

Abstract: The proteasome inhibitors of this invention include peptide-based compounds with a short linear sequence of amino acids. An oxo or thio group is attached to the N-terminal amino acid. A protein-reactive electrophilic group such as an epoxyketone, an aziridinylketone, or a beta-lactone is attached to the C-terminal amino acid. Upon contact with a proteasome complex in a target cell, the electrophilic group reacts with a functional group in or near a binding pocket or active site of the proteasome, forming a covalent bond and thereby inactivating the proteasome. These and other proteasome inhibitors can be screened for binding affinity and an ability to selectively eliminate senescent cells or cancer cells. Compounds that selectively remove senescent cells can be developed for the treatment of conditions such as osteoarthritis, ophthalmic disease, pulmonary disease, and atherosclerosis.

公开(公告)号：US20190269675A1

公开(公告)日：2019-09-05

申请号：US16403389

申请日：2019-05-03

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

Inventor： Shankar J. Chinta ,  Judith Campisi ,  Julie K. Andersen ,  Remi-Martin Laberge ,  Nathaniel David ,  James L. Kirkland ,  Tamar Tchkonia ,  Yi Zhu

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

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：US10328073B2

公开(公告)日：2019-06-25

申请号：US16054667

申请日：2018-08-03

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

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 ,  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

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：US10328058B2

公开(公告)日：2019-06-25

申请号：US15792593

申请日：2017-10-24

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

Inventor： 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: A61P9/10 ,  A61K31/496 ,  A61K31/4178 ,  A61K31/404 ,  A61K31/428 ,  A61K31/4375 ,  A61K31/5377 ,  A61K9/00 ,  A61K31/4164 ,  A61K45/06 ,  A61K47/36 ,  C12N5/00

Abstract: 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.

公开(公告)号：US10258618B2

公开(公告)日：2019-04-16

申请号：US15955542

申请日：2018-04-17

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

Inventor： 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: 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

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：US20180256568A1

公开(公告)日：2018-09-13

申请号：US15950965

申请日：2018-04-11

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 ,  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: 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 ,  A61P9/10 ,  A61P11/00 ,  A61P27/02 ,  C12N5/0081 ,  C12N2501/999 ,  C12N2503/02 ,  C12Q1/485

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：US09980962B2

公开(公告)日：2018-05-29

申请号：US15647688

申请日：2017-07-12

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

Inventor： 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: A61K31/537 ,  A61K31/496 ,  A61K31/495 ,  A61K31/5377 ,  A61K31/404 ,  A61K31/4375 ,  A61K31/428 ,  A61K45/06 ,  A61K9/00

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：US09855266B2

公开(公告)日：2018-01-02

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 Johns Hopkins University

Inventor： 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: A61K31/417 ,  A61K31/496 ,  A61K47/36 ,  A61K31/4178

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：US20170348307A1

公开(公告)日：2017-12-07

申请号：US15647688

申请日：2017-07-12

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 ,  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 ,  A61K31/5377 ,  A61K31/495 ,  A61K31/4375 ,  A61K31/428 ,  A61K45/06 ,  A61K31/404

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.