公开(公告)号：US20240342202A1

公开(公告)日：2024-10-17

申请号：US18628083

申请日：2024-04-05

Applicant: Unity Biotechnology, Inc.

Inventor： Sharon Klier ,  Jamie Dananberg

IPC: A61K31/675 ,  A61K9/00 ,  A61P27/02

CPC classification number: A61K31/675 ,  A61K9/0019 ,  A61K9/0048 ,  A61P27/02

Abstract: The present invention relates to methods of treating certain retinal vasculopathies such as diabetic macular edema, diabetic retinopathy and age-related macular degeneration, among others. The method includes treating a patient suffering from a retinal vasculopathy by administering to the patient a therapeutically effective dose of a compound as disclosed herein.

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：US20240043456A1

公开(公告)日：2024-02-08

申请号：US18032944

申请日：2020-11-10

Applicant: Unity Biotechnology, Inc.

Inventor： Liang Liao ,  Yuxi Ning ,  Jane Li ,  Yue Lu ,  Albert Shi ,  Nathan Guz

IPC: C07F9/6558

CPC classification number: C07F9/65583 ,  C07B2200/13

Abstract: Provided are the crystalline solid meglumine salts of (R)-5-(4-chlorophenyl)-1-isopropyl-2-methyl-4-(3-(4-(4-((4-((1-(phenylthio)-4-(4-((phosphonooxy)methyl)piperidin-1-yl)butan-2-yl)amino)-3- ((trifluoromethyl)sulfonyl)phenyl)sulfonamido)phenyl) piperazin-1-yl)phenyl)-1H-pyrrole-3-carboxylic acid. Pharmaceutical compositions having one or more of the crystalline solid meglumine salt compounds and methods for administering the crystalline solid meglumine salt compounds to a subject are also described. Methods for preparing the crystalline solid meglumine salt compounds are also provided.

公开(公告)号：US11111259B2

公开(公告)日：2021-09-07

申请号：US16063135

申请日：2016-12-16

Applicant: Unity Biotechnology, Inc.

Inventor： Bradley Backes ,  Thomas W. von Geldern ,  Bing Chen

IPC: C07F9/6558 ,  A61P43/00 ,  C07F9/6509

Abstract: Compounds represented by Formula (I) and (II) and salts thereof are described herein. The compounds or salts of Formula (I) and (II) may be used to treat senescence-associated diseases and disorders.

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：US20200317640A1

公开(公告)日：2020-10-08

申请号：US16897905

申请日：2020-06-10

Applicant: Unity Biotechnology, Inc.

Inventor： Anne-Marie Beausoleil ,  Ryan Hudson

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

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：US10745429B2

公开(公告)日：2020-08-18

申请号：US16425276

申请日：2019-05-29

Applicant: Unity Biotechnology, Inc.

Inventor： Anne-Marie Beausoleil ,  Ryan Hudson

IPC: C07F9/653 ,  C07F9/6533 ,  C07F9/6584 ,  A61P35/00 ,  A61P3/10 ,  A61P19/02

Abstract: This disclosure provides compounds with Bcl inhibitory activity based on a new chemical scaffold, as shown in Formula (I). The phospholidine compounds can include a P-phenyl phospholidine moiety which is substituted with an N-aryl or N-heteroaryl group. The P-phenyl phospholidine moiety can be optionally substituted at phosphorus with thio (═S) instead of oxo (═O). A second heteroatom attached to phosphorus can be cyclically linked to the N-substituted nitrogen atom of the phospholidine that is attached to the phosphorus to provide, together with the phosphorus atom through which they are connected, a heterocyclic ring. By incorporating such a cyclic constraint between two phosphorus substituents of the core linking moiety a favorable binding conformation can be promoted in the compounds. Selected compounds promote apoptosis in senescent cells, and can be developed for treating senescent-related conditions, such as osteoarthritis, ophthalmic disease, pulmonary disease, and atherosclerosis. Selected compounds promote apoptosis in cancer cells, and can be developed as chemotherapeutic agents.

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：US10550378B2

公开(公告)日：2020-02-04

申请号：US16436265

申请日：2019-06-10

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

Inventor： Serge Lichtsteiner ,  Nathaniel David

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

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.