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WO2000031238A3 - Methods and reagents for increasing proliferative capacity and preventing replicative senescence - Google Patents

Methods and reagents for increasing proliferative capacity and preventing replicative senescence Download PDF

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Publication number
WO2000031238A3
WO2000031238A3 PCT/US1999/027907 US9927907W WO0031238A3 WO 2000031238 A3 WO2000031238 A3 WO 2000031238A3 US 9927907 W US9927907 W US 9927907W WO 0031238 A3 WO0031238 A3 WO 0031238A3
Authority
WO
WIPO (PCT)
Prior art keywords
reagents
methods
proliferative capacity
replicative senescence
increasing proliferative
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/US1999/027907
Other languages
French (fr)
Other versions
WO2000031238A2 (en
Inventor
Gregory J Hannon
David H Beach
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
GENETICA Inc
Original Assignee
GENETICA Inc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by GENETICA Inc filed Critical GENETICA Inc
Priority to IL14332899A priority Critical patent/IL143328A0/en
Priority to AU21566/00A priority patent/AU2156600A/en
Priority to CA002352486A priority patent/CA2352486A1/en
Priority to EP99965890A priority patent/EP1133552A2/en
Priority to JP2000584049A priority patent/JP2002530436A/en
Publication of WO2000031238A2 publication Critical patent/WO2000031238A2/en
Publication of WO2000031238A3 publication Critical patent/WO2000031238A3/en
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/1703—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
    • A61K38/1709—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
    • C12N9/10—Transferases (2.)
    • C12N9/12—Transferases (2.) transferring phosphorus containing groups, e.g. kinases (2.7)
    • C12N9/1241—Nucleotidyltransferases (2.7.7)

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Organic Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Zoology (AREA)
  • Wood Science & Technology (AREA)
  • Epidemiology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Genetics & Genomics (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Biotechnology (AREA)
  • Biochemistry (AREA)
  • Immunology (AREA)
  • Molecular Biology (AREA)
  • Biomedical Technology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Marine Sciences & Fisheries (AREA)
  • Microbiology (AREA)
  • Dermatology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • General Engineering & Computer Science (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Enzymes And Modification Thereof (AREA)
  • Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
  • Investigating Or Analysing Biological Materials (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)
  • Cosmetics (AREA)

Abstract

The present invention relates to methods and reagents for extending the life-span, e.g. the number of mitotic divisions, of a cell. In general, the subject method relies on the activation of a telomerase activity and inhibition of one or both of an Rb/p16 pathway or a p53 pathway.
PCT/US1999/027907 1998-11-25 1999-11-24 Methods and reagents for increasing proliferative capacity and preventing replicative senescence Ceased WO2000031238A2 (en)

Priority Applications (5)

Application Number Priority Date Filing Date Title
IL14332899A IL143328A0 (en) 1998-11-25 1999-11-24 Methods and reagents for increasing proliferative capacity and preventing replicative senescence
AU21566/00A AU2156600A (en) 1998-11-25 1999-11-24 Methods and reagents for increasing proliferative capacity and preventing replicative senescence
CA002352486A CA2352486A1 (en) 1998-11-25 1999-11-24 Methods and reagents for increasing proliferative capacity and preventing replicative senescence
EP99965890A EP1133552A2 (en) 1998-11-25 1999-11-24 Methods and reagents for increasing proliferative capacity and preventing replicative senescence
JP2000584049A JP2002530436A (en) 1998-11-25 1999-11-24 Method and reagent for enhancing proliferation ability and preventing replication senescence

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US10989198P 1998-11-25 1998-11-25
US60/109.891 1998-11-25
US12054999P 1999-02-17 1999-02-17
US60/120,549 1999-02-17

Publications (2)

Publication Number Publication Date
WO2000031238A2 WO2000031238A2 (en) 2000-06-02
WO2000031238A3 true WO2000031238A3 (en) 2000-11-09

Family

ID=26807479

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US1999/027907 Ceased WO2000031238A2 (en) 1998-11-25 1999-11-24 Methods and reagents for increasing proliferative capacity and preventing replicative senescence

Country Status (6)

Country Link
EP (1) EP1133552A2 (en)
JP (1) JP2002530436A (en)
AU (1) AU2156600A (en)
CA (1) CA2352486A1 (en)
IL (1) IL143328A0 (en)
WO (1) WO2000031238A2 (en)

Families Citing this family (34)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
ES2384160T3 (en) 1999-01-13 2012-07-02 Bayer Healthcare Llc Diphenyl ureas substituted with omega-carboxy aryl as kinase inhibitors p38
US8124630B2 (en) 1999-01-13 2012-02-28 Bayer Healthcare Llc ω-carboxyaryl substituted diphenyl ureas as raf kinase inhibitors
EP1170378A1 (en) * 2000-06-26 2002-01-09 Boehringer Ingelheim International GmbH Method for monitoring the effect of cancer therapies
DE10054974A1 (en) * 2000-11-06 2002-06-06 Epigenomics Ag Diagnosis of diseases associated with Cdk4
AU2002242854A1 (en) 2001-03-21 2002-10-03 Geron Corporation Use of telomerase reverse transcriptase to create homozygous knockout animals
US7262174B2 (en) 2001-05-09 2007-08-28 Geron Corporation Treatment for wounds
WO2003066839A1 (en) * 2002-02-05 2003-08-14 Rappaport Family Institute For Research In The Medical Sciences Lineage committed stem cells selected for telomerase promoter activity
AU2003209116A1 (en) 2002-02-11 2003-09-04 Bayer Pharmaceuticals Corporation Aryl ureas with angiogenesis inhibiting activity
US20060159692A1 (en) * 2003-02-26 2006-07-20 Yoichi Taya Transcriptional factor inducing apoptosis in cancer cell
ES2288694T3 (en) 2003-05-20 2008-01-16 Bayer Pharmaceuticals Corporation DIARIL UREAS FOR DISEASES MEDIATED BY THE RECEIVER OF THE GROWTH FACTOR DERIVED FROM PLATES.
ES2716528T3 (en) 2003-06-23 2019-06-13 Telomerase Activation Sciences Inc Compositions to increase telomerase activity
US9248088B2 (en) 2003-06-25 2016-02-02 Telomerase Activation Sciences, Inc. Compositions and methods for skin conditioning
US8710012B2 (en) 2003-07-14 2014-04-29 Cls Therapeutics Limited Method for treating oncological diseases
US8431123B2 (en) 2003-07-14 2013-04-30 Cls Therapeutics Limited Method for treating systemic bacterial, fungal and protozoan infection
US8388951B2 (en) 2003-07-14 2013-03-05 Cls Therapeutics Limited Method for treating systemic DNA mutation disease
WO2006130034A1 (en) 2005-04-25 2006-12-07 Dmitry Dmitrievich Genkin Method for increasing longevity of a human being and animals
UA84156C2 (en) 2003-07-23 2008-09-25 Байер Фармасьютикалс Корпорейшн Fluoro substituted omega-carboxyaryl diphenyl urea for the treatment and prevention of diseases and conditions
PT1799269T (en) * 2004-09-28 2016-10-04 Quark Pharmaceuticals Inc Oligoribonucleotides and methods of use thereof for treatment of alopecia, acute renal failure and other diseases
JP2006325444A (en) * 2005-05-24 2006-12-07 Toyobo Co Ltd Cell growth medium
CA2628865A1 (en) * 2005-11-07 2007-05-18 The General Hospital Corporation Methods and compositions for modulation of stem cell aging
US8871200B2 (en) 2006-11-28 2014-10-28 Cls Therapeutics Limited Method for treating human diseases associated with an increased deoxyribonucleic acid content in extracellular spaces of tissues and a medicinal preparation for carrying out said method
US8987245B2 (en) 2008-04-02 2015-03-24 Jonathan R. Brestoff Parker Composition and method for affecting obesity and related conditions
US8598150B1 (en) 2008-04-02 2013-12-03 Jonathan R. Brestoff Composition and method for affecting obesity and related conditions
HUE036081T2 (en) 2009-03-09 2018-06-28 Bioatla Llc Mirac Proteins
PL2437606T3 (en) 2009-05-18 2017-07-31 Telomerase Activation Sciences, Inc. Compositions and methods for increasing telomerase activity
LT2536830T (en) 2010-02-16 2019-11-11 Ultimovacs Asa POLYPEPTIDIDES
GB201202228D0 (en) * 2012-02-08 2012-03-28 Queen Mary & Westfield College Reversal of replicative senescence
US10617743B2 (en) 2014-06-19 2020-04-14 Cls Therapeutics Limited Method to improve safety and efficacy of anti-cancer therapy
US11701410B2 (en) 2015-05-22 2023-07-18 Cls Therapeutics Limited Extracellular DNA as a therapeutic target in neurodegeneration
WO2018129563A1 (en) 2017-01-09 2018-07-12 Oisin Biotechnologies Fusogenic lipid nanoparticles and methods for manufacturing and use for therapeutic protein production and for treatment
JP2021510539A (en) 2018-01-16 2021-04-30 シーエルエス セラピューティクス リミテッドＣＬＳ Ｔｈｅｒａｐｅｕｔｉｃｓ Ｌｉｍｉｔｅｄ Treatment of diseases by liver expression of enzymes with deoxyribonuclease (DNase) activity
WO2019166702A1 (en) 2018-02-28 2019-09-06 Hagalife Use of a flash irradiation method to increase longevity and/or to delay the effects of ageing in mammals
WO2019204666A1 (en) 2018-04-18 2019-10-24 Oisin Biotechnologies, Inc. Fusogenic lipid nanoparticles and methods for the manufacture and use thereof for the target cell-specific production of a therapeutic protein and for the treatment of a disease, condition, or disorder associated with a target cell
CN113774020B (en) * 2021-08-24 2023-04-14 河北朋和生物科技有限公司 A method for constructing adipose-derived mesenchymal stem cell bank

Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0537008A1 (en) * 1991-10-11 1993-04-14 E.R. SQUIBB & SONS, INC. Use of biphosphonates for the manufacture of a medicament for blocking neoplastic transformation of cells induced by ras oncogenes
EP0618221A2 (en) * 1993-04-02 1994-10-05 Bristol-Myers Squibb Company Heterocyclic inhibitors of farnesyl protein transferase
WO1996012820A1 (en) * 1994-10-24 1996-05-02 Cold Spring Harbor Laboratory INTERACTIONS BETWEEN Raf PROTO-ONCOGENES AND CDC25 PHOSPHATASES, AND USES RELATED THERETO
US5624936A (en) * 1995-03-29 1997-04-29 Merck & Co., Inc. Inhibitors of farnesyl-protein transferase
US5721236A (en) * 1993-10-15 1998-02-24 Schering Corporation Tricyclic carbamate compounds useful for inhibition of G-protein function and for treatment of proliferative diseases
WO1998037181A2 (en) * 1997-02-20 1998-08-27 Whitehead Institute For Biomedical Research Telomerase catalytic subunit gene and encoded protein
WO1999035243A2 (en) * 1998-01-12 1999-07-15 Cold Spring Harbor Laboratory Extension of cellular lifespan, methods and reagents
WO1999042578A2 (en) * 1998-01-30 1999-08-26 Cold Spring Harbor Laboratory Modulation of cell proliferation, methods and reagents

Patent Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0537008A1 (en) * 1991-10-11 1993-04-14 E.R. SQUIBB & SONS, INC. Use of biphosphonates for the manufacture of a medicament for blocking neoplastic transformation of cells induced by ras oncogenes
EP0618221A2 (en) * 1993-04-02 1994-10-05 Bristol-Myers Squibb Company Heterocyclic inhibitors of farnesyl protein transferase
US5721236A (en) * 1993-10-15 1998-02-24 Schering Corporation Tricyclic carbamate compounds useful for inhibition of G-protein function and for treatment of proliferative diseases
WO1996012820A1 (en) * 1994-10-24 1996-05-02 Cold Spring Harbor Laboratory INTERACTIONS BETWEEN Raf PROTO-ONCOGENES AND CDC25 PHOSPHATASES, AND USES RELATED THERETO
US5624936A (en) * 1995-03-29 1997-04-29 Merck & Co., Inc. Inhibitors of farnesyl-protein transferase
WO1998037181A2 (en) * 1997-02-20 1998-08-27 Whitehead Institute For Biomedical Research Telomerase catalytic subunit gene and encoded protein
WO1999035243A2 (en) * 1998-01-12 1999-07-15 Cold Spring Harbor Laboratory Extension of cellular lifespan, methods and reagents
WO1999042578A2 (en) * 1998-01-30 1999-08-26 Cold Spring Harbor Laboratory Modulation of cell proliferation, methods and reagents

Non-Patent Citations (7)

* Cited by examiner, † Cited by third party
Title
EILEEN M. ROGAN ET AL: "Alterations in p53 and p16INK4a Expression and Telomere Length during spontaneous Immortalization of Li-Fraumeni Syndrome Fibroblasts", MOLECULAR AND CELLULAR BIOLOGY, vol. 15, no. 9, September 1995 (1995-09-01), pages 4745 - 4753, XP002142068 *
G. I. SHAPIRO ET AL: "p16INK14a Participates in a G1 arrest Checkpoint in Response to DNA Damage", MOLECULAR AND CELLULAR BIOLOGY, vol. 18, no. 1, January 1998 (1998-01-01), pages 378 - 387, XP002142070 *
M KUBBUTAT ET AL: "Regulation of p53 stability by mdm2", NATURE,GB,MACMILLAN JOURNALS LTD. LONDON, vol. 387, 15 May 1997 (1997-05-15), pages 299 - 303, XP002075660, ISSN: 0028-0836 *
M. MEYYAPPAN ET AL: "Increased Expression of Cyclin D2 during Multiple States of Growth Arrest in Primary and Established Cells", MOLECULAR AND CELLULAR BIOLOGY, vol. 18, no. 6, June 1998 (1998-06-01), pages 3163 - 3172, XP002142069 *
T. KIYONO ET AL: "both Rb/p16INK4a inactivation and telomerase activity are required to immortalize human epithelial cells", NATURE, vol. 396, 5 November 1998 (1998-11-05), pages 84 - 88, XP002142067 *
VAZIRI H ET AL: "ATM-dependent telomere loss in aging human diploid fibroblasts and DNA damage lead to the post-translational activation of p53 protein involving poly(ADP-ribose) polymerase", EMBO JOURNAL,GB,OXFORD UNIVERSITY PRESS, SURREY, vol. 16, no. 19, 1 October 1997 (1997-10-01), pages 6018 - 6033, XP002118901, ISSN: 0261-4189 *
XU H -J ET AL: "REEXPRESSION OF THE RETINOBLASTOMA PROTEIN IN TUMOR CELLS INDUCES SENESCENCE AND TELOMERASE INHIBITION", ONCOGENE,GB,BASINGSTOKE, HANTS, vol. 15, no. 21, 1 January 1997 (1997-01-01), pages 2589 - 2596, XP002068735, ISSN: 0950-9232 *

Also Published As

Publication number Publication date
JP2002530436A (en) 2002-09-17
CA2352486A1 (en) 2000-06-02
EP1133552A2 (en) 2001-09-19
AU2156600A (en) 2000-06-13
WO2000031238A2 (en) 2000-06-02
IL143328A0 (en) 2002-04-21

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