WO2006044366A3 - E2-epf5, a novel therapeutic protein and target - Google Patents

E2-epf5, a novel therapeutic protein and target Download PDF

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Publication number
WO2006044366A3
WO2006044366A3 PCT/US2005/036505 US2005036505W WO2006044366A3 WO 2006044366 A3 WO2006044366 A3 WO 2006044366A3 US 2005036505 W US2005036505 W US 2005036505W WO 2006044366 A3 WO2006044366 A3 WO 2006044366A3
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WO
WIPO (PCT)
Prior art keywords
epf5
vegf
target
inhibition
activity
Prior art date
Application number
PCT/US2005/036505
Other languages
French (fr)
Other versions
WO2006044366A2 (en
Inventor
Fred A Asselbergs
Jonathan Hall
Dieter Huesken
Mark Aron Labow
Craig Stephen Mickanin
Peter Schmid
Jan Weiler
Lorenza Wyder
Original Assignee
Novartis Ag
Novartis Pharma Gmbh
Fred A Asselbergs
Jonathan Hall
Dieter Huesken
Mark Aron Labow
Craig Stephen Mickanin
Peter Schmid
Jan Weiler
Lorenza Wyder
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 Novartis Ag, Novartis Pharma Gmbh, Fred A Asselbergs, Jonathan Hall, Dieter Huesken, Mark Aron Labow, Craig Stephen Mickanin, Peter Schmid, Jan Weiler, Lorenza Wyder filed Critical Novartis Ag
Priority to JP2007536798A priority Critical patent/JP2008516953A/en
Priority to EP05810594A priority patent/EP1802343A2/en
Priority to AU2005295863A priority patent/AU2005295863A1/en
Priority to BRPI0518132-1A priority patent/BRPI0518132A/en
Priority to CA002580883A priority patent/CA2580883A1/en
Publication of WO2006044366A2 publication Critical patent/WO2006044366A2/en
Publication of WO2006044366A3 publication Critical patent/WO2006044366A3/en

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    • 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
    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
    • C12N15/113—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing
    • C12N15/1137—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing against enzymes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7088—Compounds having three or more nucleosides or nucleotides
    • A61K31/7105—Natural ribonucleic acids, i.e. containing only riboses attached to adenine, guanine, cytosine or uracil and having 3'-5' phosphodiester links
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
    • 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
    • A61P17/06—Antipsoriatics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00—Drugs for disorders of the senses
    • A61P27/02—Ophthalmic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • 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
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/40—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against enzymes
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    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Y—ENZYMES
    • C12Y603/00—Ligases forming carbon-nitrogen bonds (6.3)
    • C12Y603/02—Acid—amino-acid ligases (peptide synthases)(6.3.2)
    • C12Y603/02019—Ubiquitin-protein ligase (6.3.2.19), i.e. ubiquitin-conjugating enzyme
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
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    • C12N2310/00—Structure or type of the nucleic acid
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    • C12N2310/11—Antisense
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    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/30—Chemical structure
    • C12N2310/32—Chemical structure of the sugar
    • C12N2310/321—2'-O-R Modification
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/30—Chemical structure
    • C12N2310/33—Chemical structure of the base
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    • C12N2310/3341—5-Methylcytosine
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    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/30—Chemical structure
    • C12N2310/34—Spatial arrangement of the modifications
    • C12N2310/341—Gapmers, i.e. of the type ===---===
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    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/30—Chemical structure
    • C12N2310/34—Spatial arrangement of the modifications
    • C12N2310/346—Spatial arrangement of the modifications having a combination of backbone and sugar modifications

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  • Health & Medical Sciences (AREA)
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  • General Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • Medicinal Chemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Molecular Biology (AREA)
  • Biochemistry (AREA)
  • Immunology (AREA)
  • Biomedical Technology (AREA)
  • Microbiology (AREA)
  • Biotechnology (AREA)
  • General Engineering & Computer Science (AREA)
  • Wood Science & Technology (AREA)
  • Zoology (AREA)
  • Biophysics (AREA)
  • Physics & Mathematics (AREA)
  • Urology & Nephrology (AREA)
  • Epidemiology (AREA)
  • Hematology (AREA)
  • Plant Pathology (AREA)
  • Food Science & Technology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Rheumatology (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Cell Biology (AREA)
  • Dermatology (AREA)
  • Virology (AREA)
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Abstract

The present invention relates to novel uses for ubiquitin conjugating enzyme E2-EPF5. In particular, inhibition of E2-EPF5 activity is shown to reduce the production VEGF, as well as other proteins regulated the transcription factor HIF-1, in response to hypoxia. Based on these findings the present invention provides therapeutic methods and pharmaceutical compositions useful for the treatment of diseases related VEGF induced angiogenesis. In addition, E2-EPF5 is provided as target for the development of therapeutics. Accordingly, the invention provides screening methods for identifying candidate compounds that inhibit E2-EPF5 activity and may therefore be used to treat VEGF induced angiogenesis such as tumor related angiogenesis. Finally, the invention also provides methods for the inhibition of VEGF and other HIF-1 regulated proteins.
PCT/US2005/036505 2004-10-14 2005-10-12 E2-epf5, a novel therapeutic protein and target WO2006044366A2 (en)

Priority Applications (5)

Application Number Priority Date Filing Date Title
JP2007536798A JP2008516953A (en) 2004-10-14 2005-10-12 E2-EPF5, novel therapeutic proteins and targets
EP05810594A EP1802343A2 (en) 2004-10-14 2005-10-12 E2-epf5, a novel therapeutic protein and target
AU2005295863A AU2005295863A1 (en) 2004-10-14 2005-10-12 E2-EPF5, a novel therapeutic protein and target
BRPI0518132-1A BRPI0518132A (en) 2004-10-14 2005-10-12 e2-epf5, an unusual protein and therapeutic target
CA002580883A CA2580883A1 (en) 2004-10-14 2005-10-12 E2-epf5, a novel therapeutic protein and target

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US61890704P 2004-10-14 2004-10-14
US60/618,907 2004-10-14

Publications (2)

Publication Number Publication Date
WO2006044366A2 WO2006044366A2 (en) 2006-04-27
WO2006044366A3 true WO2006044366A3 (en) 2007-01-04

Family

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PCT/US2005/036505 WO2006044366A2 (en) 2004-10-14 2005-10-12 E2-epf5, a novel therapeutic protein and target

Country Status (9)

Country Link
EP (1) EP1802343A2 (en)
JP (1) JP2008516953A (en)
KR (1) KR20070083640A (en)
CN (1) CN101039694A (en)
AU (1) AU2005295863A1 (en)
BR (1) BRPI0518132A (en)
CA (1) CA2580883A1 (en)
RU (1) RU2007117771A (en)
WO (1) WO2006044366A2 (en)

Families Citing this family (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR100877824B1 (en) * 2005-11-11 2009-01-12 한국생명공학연구원 E2EPF ubiquitin carrier protein-von Hippel-Lindau interaction and uses of thereof
US9066976B2 (en) 2005-11-11 2015-06-30 Korea Research Institute Of Bioscience And Biotechnology Method for therapeutic angiogenesis
ATE542897T1 (en) * 2006-06-09 2012-02-15 Yakult Honsha Kk GENE INVOLVED IN THE IMMORTALIZATION OF A HUMAN CANCER CELL AND USE THEREOF
ITMI20101030A1 (en) * 2010-06-09 2011-12-10 Sergio Capaccioli USE OF ANTISENSE OLIGONUCLEOTIDS FOR THE TREATMENT OF RETINAL DEGENERATIONS AND NEOPLASES
CN106659909B (en) * 2013-08-21 2022-01-11 德克萨斯州大学系统董事会 Compositions and methods for targeting connexin hemichannels
JP5990308B1 (en) * 2015-08-05 2016-09-14 和英 宮本 Method and device for assisting disease diagnosis, using artificial synthetic pseudo E3 as active ingredient, disease diagnosis kit using the same, and method for supporting selection of anticancer agent using the same
CN111228502A (en) * 2020-03-10 2020-06-05 新疆医科大学第三附属医院 Application of human UBE2S gene and related product

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0654530A2 (en) * 1993-06-21 1995-05-24 Rappaport Family Institute For Research In The Medical Science Ubiquitin carrier enzyme E2-F1, purification, production and use
US20030232436A1 (en) * 2002-06-14 2003-12-18 Isis Pharmaceuticals Inc. Antisense modulation of E2-EPF expression

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0654530A2 (en) * 1993-06-21 1995-05-24 Rappaport Family Institute For Research In The Medical Science Ubiquitin carrier enzyme E2-F1, purification, production and use
US20030232436A1 (en) * 2002-06-14 2003-12-18 Isis Pharmaceuticals Inc. Antisense modulation of E2-EPF expression

Non-Patent Citations (5)

* Cited by examiner, † Cited by third party
Title
FONTANINI G ET AL: "Determination of angiogenesis in human neoplasms: Current prognostic and therapeutic implications", FORUM - TRENDS IN EXPERIMENTAL AND CLINICAL MEDICINE 1998 ITALY, vol. 8, no. 2, 1998, pages 128 - 142, XP009068551, ISSN: 1121-8142 *
HARBERS KLAUS ET AL: "Provirus integration into a gene encoding a ubiquitin-conjugating enzyme results in a placental defect and embryonic lethality", PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, vol. 93, no. 22, 1996, pages 12412 - 12417, XP002387893, ISSN: 0027-8424 *
HAUSER PATRICK ET AL: "High-throughput assay to monitor formation of the E2-ubiquitin thioester intermediate.", METHODS IN ENZYMOLOGY. 2005, vol. 398, 2005, pages 87 - 100, XP009068039, ISSN: 0076-6879 *
LIU ZHI ET AL: "Characterization of a novel keratinocyte ubiquitin carrier protein", JOURNAL OF BIOLOGICAL CHEMISTRY, vol. 271, no. 5, 1996, pages 2817 - 2822, XP002387892, ISSN: 0021-9258 *
WAGNER KLAUS W ET AL: "Overexpression, genomic amplification and therapeutic potential of inhibiting the UbcH10 ubiquitin conjugase in human carcinomas of diverse anatomic origin", ONCOGENE, vol. 23, no. 39, 26 August 2004 (2004-08-26), pages 6621 - 6629, XP002387890, ISSN: 0950-9232 *

Also Published As

Publication number Publication date
EP1802343A2 (en) 2007-07-04
AU2005295863A1 (en) 2006-04-27
BRPI0518132A (en) 2008-10-28
CN101039694A (en) 2007-09-19
CA2580883A1 (en) 2006-04-27
KR20070083640A (en) 2007-08-24
WO2006044366A2 (en) 2006-04-27
JP2008516953A (en) 2008-05-22
RU2007117771A (en) 2008-11-27

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