WO2005115457A3 - Combined active and passive targeting of biologically active agents - Google Patents

Combined active and passive targeting of biologically active agents Download PDF

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Publication number
WO2005115457A3
WO2005115457A3 PCT/US2005/015681 US2005015681W WO2005115457A3 WO 2005115457 A3 WO2005115457 A3 WO 2005115457A3 US 2005015681 W US2005015681 W US 2005015681W WO 2005115457 A3 WO2005115457 A3 WO 2005115457A3
Authority
WO
WIPO (PCT)
Prior art keywords
drug
targeting
polymer
nucleus
conjugate
Prior art date
Application number
PCT/US2005/015681
Other languages
French (fr)
Other versions
WO2005115457A2 (en
Inventor
Vaikunth Cuchelkar
Pavla Kopechova
C Matthew Peterson
Jindrich Kopecek
Original Assignee
Univ Utah Res Found
Vaikunth Cuchelkar
Pavla Kopechova
C Matthew Peterson
Jindrich Kopecek
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 Univ Utah Res Found, Vaikunth Cuchelkar, Pavla Kopechova, C Matthew Peterson, Jindrich Kopecek filed Critical Univ Utah Res Found
Priority to US11/547,872 priority Critical patent/US20070287680A1/en
Priority to EP05780057A priority patent/EP1765403A4/en
Publication of WO2005115457A2 publication Critical patent/WO2005115457A2/en
Publication of WO2005115457A3 publication Critical patent/WO2005115457A3/en

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K41/00—Medicinal preparations obtained by treating materials with wave energy or particle radiation ; Therapies using these preparations
    • A61K41/0057—Photodynamic therapy with a photosensitizer, i.e. agent able to produce reactive oxygen species upon exposure to light or radiation, e.g. UV or visible light; photocleavage of nucleic acids with an agent
    • A61K41/0071—PDT with porphyrins having exactly 20 ring atoms, i.e. based on the non-expanded tetrapyrrolic ring system, e.g. bacteriochlorin, chlorin-e6, or phthalocyanines
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/54—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound
    • A61K47/554—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound the modifying agent being a steroid plant sterol, glycyrrhetic acid, enoxolone or bile acid
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/56—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule
    • A61K47/58—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. poly[meth]acrylate, polyacrylamide, polystyrene, polyvinylpyrrolidone, polyvinylalcohol or polystyrene sulfonic acid resin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/62—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being a protein, peptide or polyamino acid
    • A61K47/65—Peptidic linkers, binders or spacers, e.g. peptidic enzyme-labile linkers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/68—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
    • A61K47/6835—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site
    • A61K47/6851—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site the antibody targeting a determinant of a tumour cell
    • A61K47/6869—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site the antibody targeting a determinant of a tumour cell the tumour determinant being from a cell of the reproductive system: ovaria, uterus, testes, prostate
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/30—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
    • C07K16/3069—Reproductive system, e.g. ovaria, uterus, testes, prostate
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C07K2319/01—Fusion polypeptide containing a localisation/targetting motif
    • C07K2319/09—Fusion polypeptide containing a localisation/targetting motif containing a nuclear localisation signal

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Epidemiology (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Cell Biology (AREA)
  • Immunology (AREA)
  • Organic Chemistry (AREA)
  • Biochemistry (AREA)
  • Molecular Biology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Reproductive Health (AREA)
  • Botany (AREA)
  • Gynecology & Obstetrics (AREA)
  • Pregnancy & Childbirth (AREA)
  • Biophysics (AREA)
  • Genetics & Genomics (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Medicinal Preparation (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

Disclosed is a conjugate comprising a biologically active agent (drug) linked to a subcellular targeting moiety that targets a drug specifically to the nucleus. Targeting is achieved by attaching a steroid hormone (or an analog) to the drug. The steroid hormone attached to the drug binds its corresponding receptor; the formation of the receptor-ligand complex results in the internalization of the complex into the nucleus, thus resulting in nuclear translocation of the drug. Also disclosed is a conjugate (comprising the complex of the drug and the steroid hormone) bound to a polymer by spacers allowing for concurrent passive targeting to the tumor cell (afforded by attachment to the polymer by the EPR effect) and nuclear targeting of the conjugate (due to the presence of the steroid). Using a suitable degradable spacer allows for the release of free drug in the tumor and enhances nuclear targeting efficacy. The polymer can be further linked to a cellular targeting molecule, where the targeting molecule directs the polymer to specific cells. One may thus be able to effectively target drugs to the nucleus of tumor cells. With little or modifications, several therapeutic agents can be targeted using the invention.
PCT/US2005/015681 2004-05-10 2005-05-05 Combined active and passive targeting of biologically active agents WO2005115457A2 (en)

Priority Applications (2)

Application Number Priority Date Filing Date Title
US11/547,872 US20070287680A1 (en) 2004-05-10 2005-05-05 Combined Active and Passive Targeting of Biologically Active Agents
EP05780057A EP1765403A4 (en) 2004-05-10 2005-05-05 Combined active and passive targeting of biologically active agents

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US56977004P 2004-05-10 2004-05-10
US60/569,770 2004-05-10

Publications (2)

Publication Number Publication Date
WO2005115457A2 WO2005115457A2 (en) 2005-12-08
WO2005115457A3 true WO2005115457A3 (en) 2009-04-09

Family

ID=35451414

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2005/015681 WO2005115457A2 (en) 2004-05-10 2005-05-05 Combined active and passive targeting of biologically active agents

Country Status (2)

Country Link
EP (1) EP1765403A4 (en)
WO (1) WO2005115457A2 (en)

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CA2827029C (en) 2011-02-11 2019-07-02 The Regents Of The University Of Michigan Tripeptide compositions and methods
CN111454302B (en) * 2020-04-30 2022-07-05 大连理工大学 Chlorin e6 ferrocene conjugate with light and sound sensitive activity, preparation method and application

Family Cites Families (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5618528A (en) * 1994-02-28 1997-04-08 Sterling Winthrop Inc. Biologically compatible linear block copolymers of polyalkylene oxide and peptide units
US6210717B1 (en) * 1997-12-12 2001-04-03 Samyang Corporation Biodegradable mixed polymeric micelles for gene delivery
EP1286700A2 (en) * 2000-06-01 2003-03-05 Universite Catholique De Louvain Tumor activated prodrug compounds
WO2002044324A2 (en) * 2000-10-06 2002-06-06 Xenoport, Inc. Bile-acid derived compounds for enhancing oral absorption and systemic bioavailability of drugs
US7060498B1 (en) * 2001-11-28 2006-06-13 Genta Salus Llc Polycationic water soluble copolymer and method for transferring polyanionic macromolecules across biological barriers
SE0200531D0 (en) * 2002-02-22 2002-02-22 Avaris Ab Novel biomolecular complexes, method for their production and use
US7662360B2 (en) * 2002-07-22 2010-02-16 Psimei Pharmaceuticals Plc Conjugates of N-hydroxypropymethacrylamide-methacrylate copolymer with nuclide activation agent and/or anti-cancer compounds

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
PUTNAM ET AL.: "Polymer conjugates with anticancer activity", ADVANCES IN POLYMER SCIENCES, vol. 122, 1995, pages 57 - 123, XP001525573 *
REBUFFAT ET AL.: "Selective enhancement of gene transfer by steroid-mediated gene delivery.", NATURE BIOTECHNOLOGY, vol. 19, December 2001 (2001-12-01), pages 1155 - 1161, XP002444472 *
See also references of EP1765403A4 *

Also Published As

Publication number Publication date
WO2005115457A2 (en) 2005-12-08
EP1765403A4 (en) 2011-03-30
EP1765403A2 (en) 2007-03-28

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