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：US20190382371A1

公开(公告)日：2019-12-19

申请号：US16446360

申请日：2019-06-19

Applicant: Unity Biotechnology, Inc.

Inventor： Anne-Marie Beausoleil ,  Ryan Hudson

IPC: C07D401/10 ,  C07D403/10 ,  C07D401/14 ,  A61P35/00 ,  A61P27/00 ,  A61P9/10

Abstract: The aryl sulfonamide compounds of this invention have powerful and cell-type specific Bcl inhibitory activity. Selected compounds in this class promote apoptosis in senescent cells, and are being developed for treating senescent-related conditions. Selected compounds in this class promote apoptosis in cancer cells, and can be developed as chemotherapeutic agents.

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：US20190248837A1

公开(公告)日：2019-08-15

申请号：US16393651

申请日：2019-04-24

Applicant: UNITY BIOTECHNOLOGY, INC.

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

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

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：US20190136215A1

公开(公告)日：2019-05-09

申请号：US16029244

申请日：2018-07-06

Applicant: Unity Biotechnology, Inc. ,  Kythera Biopharmaceuticals, Inc.

Inventor： Serge Lichtsteiner ,  Nathaniel David

IPC: C12N9/50 ,  C12N15/85 ,  A61K38/48

CPC classification number: C12N9/50 ,  A61K38/4873 ,  C12N15/85 ,  C12N2740/10043 ,  C12N2740/15043 ,  C12Y304/22

Abstract: Polypeptides, viruses, methods and compositions provided herein are useful for the selective elimination of senescent cells. Method aspects include methods for inducing apoptosis in a senescent cell comprising administering to the cell a polynucleotide, virus, host cell, or pharmaceutical composition described herein. Other methods include expressing a pro-apoptotic gene in a senescent cell comprising administering to the cell the polynucleotide, virus, or pharmaceutical composition as described herein.

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.

公开(公告)号：US20180215791A1

公开(公告)日：2018-08-02

申请号：US15937255

申请日：2018-03-27

Applicant: Unity Biotechnology, Inc.

Inventor： Shayne Squires

IPC: C07K14/00 ,  G01N33/574 ,  A61K47/64 ,  A61K47/68 ,  A61K35/12 ,  A61K38/10 ,  A61K38/16 ,  G01N33/50 ,  C12N15/86 ,  C12N15/10 ,  C07K16/28 ,  A61K51/10 ,  A61K51/08 ,  A61K49/00 ,  A61K39/00

Abstract: Disclosed are agents (e.g., peptides, polypeptides, proteins, small molecules, antibodies, and antibody fragments that target senescent cells) and methods of their use for imaging senescent cells in vivo and for treating or preventing cancer, age-related disease, tobacco-related disease, or other diseases and disorders related to or caused by cellular senescence in a mammal. The methods include administering one or more of the agents of the invention to a mammal, e.g., a human. The agents, which specifically bind to senescent cells, can be labeled with a radioactive label or a therapeutic label, e.g., a cytotoxic agent.

公开(公告)号：US20180193359A1

公开(公告)日：2018-07-12

申请号：US15915989

申请日：2018-03-08

Applicant: Unity Biotechnology, Inc.

Inventor： Nathaniel David

IPC: A61K31/575 ,  A61K31/166 ,  A61K9/00 ,  A61K31/11 ,  A61K31/4178 ,  A61K31/138 ,  A61K31/05 ,  A61K31/496 ,  A61K31/433 ,  A61K31/427 ,  A61K31/426 ,  A61K31/4741 ,  A61K31/352 ,  A61K31/4709 ,  A61K31/541 ,  A61K31/167 ,  A61K31/365 ,  A61K31/4025 ,  A61K31/122

CPC classification number: A61K31/575 ,  A61K9/0019 ,  A61K31/05 ,  A61K31/11 ,  A61K31/122 ,  A61K31/138 ,  A61K31/166 ,  A61K31/167 ,  A61K31/352 ,  A61K31/365 ,  A61K31/4025 ,  A61K31/4178 ,  A61K31/426 ,  A61K31/427 ,  A61K31/433 ,  A61K31/4709 ,  A61K31/4741 ,  A61K31/496 ,  A61K31/541

Abstract: Disclosed herein are compounds that are effective for treatment of various disease states associated with senescence. The disclosed compounds can be used to eliminate senescent cells for disease treatment. The dosing of the compounds includes both single administration and regimens of cycling dosages.