公开(公告)号：US12285427B2

公开(公告)日：2025-04-29

申请号：US18215731

申请日：2023-08-07

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 ,  Bennett G. Childs ,  Jan M. A. Van Deursen ,  Nathaniel David ,  Alain Philippe Vasserot

IPC: A61K31/496 ,  A61K9/00 ,  A61K31/404 ,  A61K31/4178 ,  A61K31/428 ,  A61K31/4375 ,  A61K31/495 ,  A61K31/5377 ,  A61K31/728 ,  A61K45/06 ,  A61K47/36 ,  A61P9/10 ,  A61P11/00 ,  A61P25/16 ,  A61P27/02 ,  C12N5/00 ,  A61P25/28 ,  C12Q1/48

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：US20240115563A1

公开(公告)日：2024-04-11

申请号：US18215731

申请日：2023-08-07

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 ,  Bennett G. Childs ,  Jan M. A. Van Deursen ,  Nathaniel David ,  Alain Philippe Vasserot

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

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 ,  A61P9/10 ,  A61P11/00 ,  A61P25/16 ,  A61P27/02 ,  C12N5/0081 ,  C12N2503/02 ,  C12Q1/485

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：US20210169875A1

公开(公告)日：2021-06-10

申请号：US17114376

申请日：2020-12-07

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

Inventor： Remi-Martin Laberge ,  Judith Campisi ,  Albert Davalos ,  Marco Demaria ,  Nathaniel David ,  Jan M.A. van Deursen ,  Darren J. Baker ,  Bennett G. Childs

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

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：US20200338097A1

公开(公告)日：2020-10-29

申请号：US16899401

申请日：2020-06-11

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

Inventor： Nathaniel David ,  Remi-Martin Laberge

IPC: 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：US10689416B2

公开(公告)日：2020-06-23

申请号：US16393651

申请日：2019-04-24

Applicant: UNITY BIOTECHNOLOGY, INC.

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

IPC: C07K7/06 ,  A61K38/06 ,  A61P27/02 ,  A61P9/10 ,  A61P19/02 ,  A61P35/00 ,  A61K31/496 ,  A61K31/519 ,  A61K38/05 ,  A61K38/07 ,  C07D201/00 ,  C07D303/32 ,  C07K5/06 ,  C07K5/08 ,  C07K5/083 ,  C07K5/10 ,  C07K5/107 ,  A61K38/00

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：US10519197B1

公开(公告)日：2019-12-31

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: A61K38/00 ,  C07K7/06 ,  C07K5/10 ,  C07K5/06 ,  A61P35/00 ,  C07K5/08 ,  C07D303/32

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：US10478432B2

公开(公告)日：2019-11-19

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 ,  A61P27/02 ,  A61K9/00 ,  A61P11/00 ,  A61P9/10 ,  A61K31/428 ,  A61K31/495 ,  A61K31/5377 ,  A61K31/404 ,  A61K31/4375 ,  A61K45/06 ,  A61K31/4178 ,  A61K31/728 ,  C12N5/00 ,  A61K47/36 ,  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：US10413542B2

公开(公告)日：2019-09-17

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

Inventor： Remi-Martin Laberge ,  Nathaniel David ,  Alain Philippe Vasserot ,  Darren J. Baker ,  Bennett G. Childs ,  James L. Kirkland ,  Tamar Tchkonia ,  Jan M. A. van Deursen ,  Yi Zhu

IPC: A61K31/4375 ,  A61P11/00 ,  A61P9/10 ,  A61P19/02 ,  A61K31/496 ,  A61P27/02 ,  A61K31/428 ,  A61K31/495 ,  A61K31/5377 ,  A61K31/404 ,  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：US10213426B2

公开(公告)日：2019-02-26

申请号：US15455684

申请日：2017-03-10

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

Inventor： Remi-Martin Laberge ,  Judith Campisi ,  Albert Davalos ,  Marco Demaria ,  Nathaniel David ,  Yi Zhu ,  James L. Kirkland ,  Tamar Tchkonia

IPC: G01N1/00 ,  C12Q1/00 ,  A61K31/496 ,  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：US20180250296A1

公开(公告)日：2018-09-06

申请号：US15981696

申请日：2018-05-16

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

Inventor： Remi-Martin Laberge ,  James L. Kirkland ,  Tamar Tchkonia ,  Yi Zhu ,  Nathaniel David ,  Alain Philippe Vasserot ,  Darren J. Baker ,  Bennett G. Childs ,  Jan M.A. van Deursen

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

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.