公开(公告)号：US09980962B2

公开(公告)日：2018-05-29

申请号：US15647688

申请日：2017-07-12

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

发明人： 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分类号： A61K31/537 ,  A61K31/496 ,  A61K31/495 ,  A61K31/5377 ,  A61K31/404 ,  A61K31/4375 ,  A61K31/428 ,  A61K45/06 ,  A61K9/00

CPC分类号： 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

摘要： 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：US09926280B2

公开(公告)日：2018-03-27

申请号：US14928775

申请日：2015-10-30

申请人： Buck Institute for Research on Aging

发明人： Varghese John ,  Dale E. Bredesen

IPC分类号： C07D233/88 ,  C07D233/76 ,  C07D233/70 ,  A61K31/4439 ,  A61K31/4168 ,  A61K31/4166 ,  C07D401/10 ,  C07D401/04 ,  A61K45/06 ,  A61K31/46 ,  A61K31/506 ,  C07D403/10

CPC分类号： C07D233/76 ,  A61K31/4166 ,  A61K31/4168 ,  A61K31/4439 ,  A61K31/46 ,  A61K31/506 ,  A61K45/06 ,  C07D233/70 ,  C07D233/88 ,  C07D401/04 ,  C07D401/10 ,  C07D403/10 ,  A61K2300/00

摘要： In certain embodiments hydantoin compounds are provided herein that are effective to inhibit BACE activity against APP. Without being bound to a particular theory, it is believed the activity of the hydantoins identified herein appears to be associated with binding to BACE and/or to APP particularly when these moieties form a BACE/APP complex. Accordingly, it is believed the compounds described herein represent a new class of compounds designated herein as APP-Binding-BACE Inhibitors (ABBIs) and provide a new mechanism to modulate APP processing. The hydantoins described herein appear to show improved brain permeability and functional BACE inhibition.

公开(公告)号：US09884065B2

公开(公告)日：2018-02-06

申请号：US15077630

申请日：2016-03-22

申请人： Buck Institute for Research on Aging

发明人： Judith Campisi ,  Remi-Martin Laberge ,  Francis Rodier ,  Marco Demaria

IPC分类号： A61P35/04 ,  A61K31/56 ,  A61K31/573 ,  G01N33/50 ,  A61K31/352 ,  A61K45/06

CPC分类号： A61K31/573 ,  A01K67/0275 ,  A01K2217/052 ,  A01K2217/30 ,  A01K2227/105 ,  A01K2267/0331 ,  A01K2267/0393 ,  A61K31/352 ,  A61K31/4545 ,  A61K31/522 ,  A61K38/085 ,  A61K38/28 ,  A61K39/21 ,  A61K45/06 ,  A61N5/10 ,  A61N2005/1089 ,  G01N33/5011 ,  G01N33/502 ,  G01N33/5023 ,  G01N33/5044 ,  G01N2500/10

摘要： Methods are provided herein for enhancing the effectiveness of medical therapies by administering agents that suppress a biological damage response that is inducible by the medical therapy administered to a subject. In certain embodiments, a method is provided for administering an anti-senescent cell agent that suppresses a biological response comprising cellular senescence that is induced by the medical therapy.

公开(公告)号：US09855266B2

公开(公告)日：2018-01-02

申请号：US15467129

申请日：2017-03-23

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

发明人： 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分类号： A61K31/417 ,  A61K31/496 ,  A61K47/36 ,  A61K31/4178

CPC分类号： 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

摘要： 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：US09245290B2

公开(公告)日：2016-01-26

申请号：US13968338

申请日：2013-08-15

申请人： Buck Institute for Research on Aging ,  The Regents of the University of California

发明人： Lisa M. Ellerby ,  Jonathan A. Ellman ,  Melissa J. Leyva

IPC分类号： C07D405/12 ,  G06Q30/06 ,  C07D249/04

CPC分类号： G06Q30/0627 ,  C07D249/04 ,  C07D405/12

摘要： This invention provides novel caspase inhibitors useful for prophylaxis or treatment of a number of pathologies, including, for example, Huntington's disease. In certain embodiments the inhibitors include inhibitors of casepase-3 and/or casepase-6.

公开(公告)号：US09040259B2

公开(公告)日：2015-05-26

申请号：US13046304

申请日：2011-03-11

申请人： Matthew Alan Gregory ,  Sabine Gaisser ,  Hrvoje Petkovic ,  Steven Moss

发明人： Matthew Alan Gregory ,  Sabine Gaisser ,  Hrvoje Petkovic ,  Steven Moss

IPC分类号： C12P19/62 ,  C12P17/18 ,  C07D471/18 ,  C07D487/18 ,  C07D493/18 ,  C07K14/36 ,  C12N15/52 ,  C12N15/70 ,  C12N15/76 ,  C12N1/20

CPC分类号： C07D498/18 ,  C07D405/12 ,  C07D471/18 ,  C07D487/18 ,  C07D493/18 ,  C07K14/36 ,  C12N15/52 ,  C12N15/70 ,  C12N15/76 ,  C12P17/188

摘要： The present invention relates to production of polyketides and other natural products and to libraries of compounds and individual novel compounds. One important area is the isolation and potential use of novel FKBP-ligand analogs and host cells that produce these compounds. The invention is particularly concerned with methods for the efficient transformation of strains that produce FKBP analogs and recombinant cells in which cloned genes or gene cassettes are expressed to generate novel compounds such as polyketide (especially rapamycin) FKBP-ligand analogs, and to processes for their preparation, and to means employed therein (e.g. nucleic acids, vectors, gene cassettes and genetically modified strains).

摘要翻译： 本发明涉及聚酮化合物和其它天然产物的生产以及化合物和单个新化合物的文库。 一个重要的领域是产生这些化合物的新型FKBP-配体类似物和宿主细胞的分离和潜在用途。 本发明特别涉及用于产生FKBP类似物和重组细胞的菌株的有效转化的方法，其中克隆的基因或基因盒被表达以产生新的化合物，例如聚酮化合物（特别是雷帕霉素）FKBP-配体类似物， 制备和其中使用的手段（例如核酸，载体，基因盒和遗传修饰的菌株）。

公开(公告)号：US20130344603A1

公开(公告)日：2013-12-26

申请号：US13880969

申请日：2011-10-20

申请人： Victoria V. Lunyak

发明人： Victoria V. Lunyak

IPC分类号： C12N5/074

CPC分类号： C12N5/0607 ,  C12N5/0667 ,  C12N5/0696 ,  C12N2310/531 ,  C12N2501/65 ,  C12N2510/00 ,  C12N2310/13 ,  C12N2330/10

摘要： In certain embodiments methods are provided for inducing and/or restoring and/or maintaining a non-senescent phenotype, or aspects thereof (e.g., proliferative capacity and/or pluripotency) in a mammalian cell. The methods typically involve reducing the level or activity of SINE/Alu retrotransposon transcripts in the cell in an amount sufficient to induce or restore proliferative capacity and/or pluripotency to said mammalian cell.

摘要翻译： 在某些实施方案中，提供了用于在哺乳动物细胞中诱导和/或恢复和/或维持非衰老表型或其方面（例如，增殖能力和/或多能性）的方法。 所述方法通常包括以足以诱导或恢复所述哺乳动物细胞的增殖能力和/或多能性的量降低细胞中SINE / Alu反转录转录物转录物的水平或活性。

公开(公告)号：US20130065254A1

公开(公告)日：2013-03-14

申请号：US13593265

申请日：2012-08-23

申请人： VICTORIA V. LUNYAK

发明人： VICTORIA V. LUNYAK

IPC分类号： C07K16/18 ,  G01N33/566 ,  G01N21/64 ,  G01N21/76 ,  C12M1/34 ,  G01N27/26 ,  G01N27/72 ,  C12P21/00 ,  C12P21/08 ,  C12N9/96 ,  G01N21/78

CPC分类号： C07K16/18 ,  C07K16/44 ,  C07K2317/34 ,  G01N33/6875 ,  G01N2440/12 ,  G01N2500/00 ,  G01N2800/52 ,  G01N2800/7042

摘要： This invention pertains to markers of cellular senescence. In particular methylation of histone H1 (or isoforms thereof) at residue 172 and/or at residue 180 is a marker of cellular senescence. Antibodies specific to histone H1 (or isoforms thereof) methylated at residue 172 and/or at residue 180 are provided.

摘要翻译： 本发明涉及细胞衰老的标志物。 特别地，在残基172和/或残基180处的组蛋白H1（或其同种型）的甲基化是细胞衰老的标志物。 提供了在残基172和/或残基180处甲基化的组蛋白H1（或其同种型）特异的抗体。

公开(公告)号：US20120244567A1

公开(公告)日：2012-09-27

申请号：US13392487

申请日：2010-09-03

申请人： Xianmin Zeng

发明人： Xianmin Zeng

IPC分类号： C12N5/0735 ,  C12N5/071 ,  C12Q1/32 ,  C12Q1/48 ,  C12N5/0797 ,  C12Q1/18

CPC分类号： C12N5/0606 ,  C12N2501/115 ,  C12N2502/13 ,  C12N2503/02 ,  C12N2533/90 ,  G01N33/5014 ,  G01N33/5073

摘要： Methods of culturing embryonic stem cells in a format suitable for high-throughput screening (HTS) are provided. In addition compounds that show differential cytotoxic/protective activity on embryonic stem cells (ESCs) and neurological stem cells (NSCs) are provided.

摘要翻译： 提供了以适合高通量筛选（HTS）的方式培养胚胎干细胞的方法。 此外，还提供了对胚胎干细胞（ESC）和神经干细胞（NSCs）显示出差异细胞毒性/保护活性的化合物。

公开(公告)号：US20120129834A1

公开(公告)日：2012-05-24

申请号：US13234891

申请日：2011-09-16

申请人： ROBERT HUGHES ,  LISA ELLERBY

发明人： ROBERT HUGHES ,  LISA ELLERBY

IPC分类号： A61K31/4535 ,  A61K31/451 ,  A61P25/00 ,  A61K31/4545 ,  A61P25/28 ,  A61K31/553 ,  A61P25/14

CPC分类号： A61K31/553 ,  A61K31/451 ,  A61K31/4535

摘要： Methods are provided for the treatment and/or prophylaxis of Huntington's disease. In various embodiments the methods involve administration of one or more serotonin receptor antagonists. In certain embodiments the serotonin receptor antagonists include, but are not limited to loxapine, and/or a loxapine analogue, and/or cyproheptadine, and/or a cyproheptadine analogue (e.g., pizotifen).

摘要翻译： 提供了用于治疗和/或预防亨廷顿氏病的方法。 在各种实施方案中，所述方法包括施用一种或多种5-羟色胺受体拮抗剂。 在某些实施方案中，5-羟色胺受体拮抗剂包括但不限于洛沙平和/或洛沙平类似物和/或赛庚啶和/或赛庚啶类似物（例如匹司他芬）。