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WO2008134069A3 - Anchored ligand agents - Google Patents

Anchored ligand agents Download PDF

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Publication number
WO2008134069A3
WO2008134069A3 PCT/US2008/005528 US2008005528W WO2008134069A3 WO 2008134069 A3 WO2008134069 A3 WO 2008134069A3 US 2008005528 W US2008005528 W US 2008005528W WO 2008134069 A3 WO2008134069 A3 WO 2008134069A3
Authority
WO
WIPO (PCT)
Prior art keywords
ligand
target
target molecule
binding
active site
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/US2008/005528
Other languages
French (fr)
Other versions
WO2008134069A2 (en
Inventor
Weihong Tan
Zehui Cao
Youngmi Kim
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.)
University of Florida
University of Florida Research Foundation Inc
Original Assignee
University of Florida
University of Florida Research Foundation 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 University of Florida, University of Florida Research Foundation Inc filed Critical University of Florida
Publication of WO2008134069A2 publication Critical patent/WO2008134069A2/en
Publication of WO2008134069A3 publication Critical patent/WO2008134069A3/en
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • 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
    • C12N15/115—Aptamers, i.e. nucleic acids binding a target molecule specifically and with high affinity without hybridising therewith ; Nucleic acids binding to non-nucleic acids, e.g. aptamers
    • 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
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/10—Type of nucleic acid
    • C12N2310/16—Aptamers
    • 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
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/30—Chemical structure
    • C12N2310/35—Nature of the modification
    • C12N2310/351—Conjugate
    • 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
    • C12N2320/00—Applications; Uses
    • C12N2320/50—Methods for regulating/modulating their activity

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Genetics & Genomics (AREA)
  • Biomedical Technology (AREA)
  • Chemical & Material Sciences (AREA)
  • Molecular Biology (AREA)
  • Organic Chemistry (AREA)
  • Biotechnology (AREA)
  • General Engineering & Computer Science (AREA)
  • Zoology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Wood Science & Technology (AREA)
  • Microbiology (AREA)
  • Plant Pathology (AREA)
  • Physics & Mathematics (AREA)
  • Biochemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Biophysics (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

The invention provides novel therapeutic agents comprising ligand molecules such as aptamers linked to a molecular anchor (MA). In the absence of a MA, ligands rapidly diffuse into bulk solution after dissociation from a target molecule. With a MA tightly bound to the target molecule, anchored ligand molecules of the invention remain in close proximity to the active site on the target molecule, even after dissociating from the target, permitting rapid re- binding of ligand to its target. Reversibility of binding to the active site can be effectively and rapidly achieved using antidotes based on the complementary DNA sequences. A preferred embodiment in accordance with the invention is a highly efficient anticoagulant agent that demonstrates binding efficiency to thrombin that is increased many fold relative to a corresponding unanchored aptamer-based ligand.
PCT/US2008/005528 2007-04-26 2008-04-28 Anchored ligand agents Ceased WO2008134069A2 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US91424207P 2007-04-26 2007-04-26
US60/914,242 2007-04-26

Publications (2)

Publication Number Publication Date
WO2008134069A2 WO2008134069A2 (en) 2008-11-06
WO2008134069A3 true WO2008134069A3 (en) 2009-02-12

Family

ID=39926277

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2008/005528 Ceased WO2008134069A2 (en) 2007-04-26 2008-04-28 Anchored ligand agents

Country Status (1)

Country Link
WO (1) WO2008134069A2 (en)

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5756291A (en) * 1992-08-21 1998-05-26 Gilead Sciences, Inc. Aptamers specific for biomolecules and methods of making
US20020037506A1 (en) * 2000-04-18 2002-03-28 Yun Lin Aptamer based two-site binding assay
US20030175703A1 (en) * 2000-09-26 2003-09-18 Sullenger Bruce A. RNA aptamers and methods for identifying the same
US20050123936A1 (en) * 2003-01-16 2005-06-09 Ansari Aseem Z. Method, composition, and kit to design, evaluate, and/or test compounds that modulate regulatory factor binding to nucleic acids
WO2007025049A2 (en) * 2005-08-26 2007-03-01 Archemix Corp. Aptamers that bind thrombin with high affinity

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5756291A (en) * 1992-08-21 1998-05-26 Gilead Sciences, Inc. Aptamers specific for biomolecules and methods of making
US20020037506A1 (en) * 2000-04-18 2002-03-28 Yun Lin Aptamer based two-site binding assay
US20030175703A1 (en) * 2000-09-26 2003-09-18 Sullenger Bruce A. RNA aptamers and methods for identifying the same
US20050123936A1 (en) * 2003-01-16 2005-06-09 Ansari Aseem Z. Method, composition, and kit to design, evaluate, and/or test compounds that modulate regulatory factor binding to nucleic acids
WO2007025049A2 (en) * 2005-08-26 2007-03-01 Archemix Corp. Aptamers that bind thrombin with high affinity

Also Published As

Publication number Publication date
WO2008134069A2 (en) 2008-11-06

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