WO2001036005A3 - Targeted delivery of therapeutic and diagnostic moieties - Google Patents

Targeted delivery of therapeutic and diagnostic moieties Download PDF

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Publication number
WO2001036005A3
WO2001036005A3 PCT/US2000/031424 US0031424W WO0136005A3 WO 2001036005 A3 WO2001036005 A3 WO 2001036005A3 US 0031424 W US0031424 W US 0031424W WO 0136005 A3 WO0136005 A3 WO 0136005A3
Authority
WO
WIPO (PCT)
Prior art keywords
therapeutic
monoclonal antibodies
target cell
internalized
conjugated
Prior art date
Application number
PCT/US2000/031424
Other languages
French (fr)
Other versions
WO2001036005A2 (en
Inventor
Michael Press
Jinha Park
Original Assignee
Univ Southern California
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 Southern California filed Critical Univ Southern California
Priority to CA002391450A priority Critical patent/CA2391450A1/en
Priority to EP00977241A priority patent/EP1231944A2/en
Priority to AU14908/01A priority patent/AU1490801A/en
Priority to JP2001537995A priority patent/JP2003523178A/en
Publication of WO2001036005A2 publication Critical patent/WO2001036005A2/en
Publication of WO2001036005A3 publication Critical patent/WO2001036005A3/en

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K49/00—Preparations for testing in vivo
    • A61K49/001—Preparation for luminescence or biological staining
    • A61K49/0013—Luminescence
    • A61K49/0017—Fluorescence in vivo
    • A61K49/005—Fluorescence in vivo characterised by the carrier molecule carrying the fluorescent agent
    • A61K49/0058—Antibodies
    • 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
    • A61K47/6849—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 receptor, a cell surface antigen or a cell surface determinant
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K49/00—Preparations for testing in vivo
    • A61K49/06—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations
    • A61K49/08—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by the carrier
    • A61K49/10—Organic compounds
    • A61K49/14—Peptides, e.g. proteins
    • A61K49/16—Antibodies; Immunoglobulins; Fragments thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K51/00—Preparations containing radioactive substances for use in therapy or testing in vivo
    • A61K51/02—Preparations containing radioactive substances for use in therapy or testing in vivo characterised by the carrier, i.e. characterised by the agent or material covalently linked or complexing the radioactive nucleus
    • A61K51/04—Organic compounds
    • A61K51/08—Peptides, e.g. proteins, carriers being peptides, polyamino acids, proteins
    • A61K51/10—Antibodies or immunoglobulins; Fragments thereof, the carrier being an antibody, an immunoglobulin or a fragment thereof, e.g. a camelised human single domain antibody or the Fc fragment of an antibody
    • A61K51/1045—Antibodies or immunoglobulins; Fragments thereof, the carrier being an antibody, an immunoglobulin or a fragment thereof, e.g. a camelised human single domain antibody or the Fc fragment of an antibody against animal or human tumor cells or tumor cell determinants
    • 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
    • A61P25/00—Drugs for disorders of the nervous system
    • 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
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
    • 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
    • C07K16/32—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against translation products of oncogenes
    • 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
    • A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
    • C07K2317/77—Internalization into the cell

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Engineering & Computer Science (AREA)
  • Organic Chemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Immunology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Epidemiology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Cell Biology (AREA)
  • Oncology (AREA)
  • Biomedical Technology (AREA)
  • Neurology (AREA)
  • Optics & Photonics (AREA)
  • Neurosurgery (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Dermatology (AREA)
  • Cardiology (AREA)
  • Vascular Medicine (AREA)
  • Urology & Nephrology (AREA)
  • Physics & Mathematics (AREA)
  • Ophthalmology & Optometry (AREA)
  • Biochemistry (AREA)
  • Biophysics (AREA)
  • Genetics & Genomics (AREA)
  • Molecular Biology (AREA)
  • Radiology & Medical Imaging (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Peptides Or Proteins (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Medicinal Preparation (AREA)

Abstract

Compositions and methods for improving cellular internalization of one or more compounds are disclosed. The invention provides a drug conjugate composition that can be delivered to a target cell, which comprises a carrier compound that has a binding specificity for a receptor molecule and is conjugated to a therapeutic or diagnostic moiety. When this composition is administered to a subject, the carrier compound binds to the receptor and is internalized by the target cell. Furthermore, monoclonal antibodies are disclosed that are internalized into target cells. The monoclonal antibodies of the invention are specific for target cells, particularly for cells expressing the surface antigen p185HER-2. The antibodies of the invention may be conjugated with a molecule for delivery into a target cell. Such molecules may be used for therapeutic treatment, including gene therapy, and for imaging. The invention also provides DNA sequences of the variable regions of particular monoclonal antibodies.
PCT/US2000/031424 1999-11-15 2000-11-15 Targeted delivery of therapeutic and diagnostic moieties WO2001036005A2 (en)

Priority Applications (4)

Application Number Priority Date Filing Date Title
CA002391450A CA2391450A1 (en) 1999-11-15 2000-11-15 Targeted delivery of therapeutic and diagnostic moieties
EP00977241A EP1231944A2 (en) 1999-11-15 2000-11-15 Targeted delivery of therapeutic and diagnostic moieties
AU14908/01A AU1490801A (en) 1999-11-15 2000-11-15 Targeted delivery of therapeutic and diagnostic moieties
JP2001537995A JP2003523178A (en) 1999-11-15 2000-11-15 Targeted delivery of therapeutic or diagnostic ingredients

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US16556399P 1999-11-15 1999-11-15
US60/165,563 1999-11-15

Publications (2)

Publication Number Publication Date
WO2001036005A2 WO2001036005A2 (en) 2001-05-25
WO2001036005A3 true WO2001036005A3 (en) 2002-01-24

Family

ID=22599451

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2000/031424 WO2001036005A2 (en) 1999-11-15 2000-11-15 Targeted delivery of therapeutic and diagnostic moieties

Country Status (5)

Country Link
EP (1) EP1231944A2 (en)
JP (1) JP2003523178A (en)
AU (1) AU1490801A (en)
CA (1) CA2391450A1 (en)
WO (1) WO2001036005A2 (en)

Families Citing this family (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20030049262A1 (en) * 1998-10-02 2003-03-13 Susan Love Methods for identification, diagnosis, and treatment of breast cancer
EP1797431B1 (en) * 2004-10-06 2011-01-26 Wellstat Biologics Corporation Detection of elevated levels of her-2/neu protein on circulating cancer cells and treatment
WO2008093166A2 (en) 2006-05-11 2008-08-07 Ghent University Sialoadhesin-related compositions and methods
KR102283200B1 (en) * 2012-03-14 2021-07-29 리제너론 파마슈티칼스 인코포레이티드 Multispecific antigen-binding molecules and uses thereof
IL313163B2 (en) 2015-07-06 2025-06-01 Regeneron Pharma Multispecific antigen-binding molecules and their uses
EP3448891A1 (en) 2016-04-28 2019-03-06 Regeneron Pharmaceuticals, Inc. Methods of making multispecific antigen-binding molecules
AU2018224094B2 (en) 2017-02-24 2025-04-17 Macrogenics, Inc. Bispecific binding molecules that are capable of binding CD137 and tumor antigens, and uses thereof
JP7348844B2 (en) 2017-06-07 2023-09-21 リジェネロン・ファーマシューティカルズ・インコーポレイテッド Compositions and methods for internalizing enzymes
EP3788075A1 (en) 2018-04-30 2021-03-10 Regeneron Pharmaceuticals, Inc. Antibodies, and bispecific antigen-binding molecules that bind her2 and/or aplp2, conjugates, and uses thereof
KR20250140631A (en) 2018-05-17 2025-09-25 리제너론 파마슈티칼스 인코포레이티드 Anti-cd63 antibodies, conjugates, and uses thereof

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1993017715A1 (en) * 1992-03-05 1993-09-16 Board Of Regents, The University Of Texas System Diagnostic and/or therapeutic agents, targeted to neovascular endothelial cells
WO2001000244A2 (en) * 1999-06-25 2001-01-04 Genentech, Inc. METHODS OF TREATMENT USING ANTI-ErbB ANTIBODY-MAYTANSINOID CONJUGATES
WO2001021192A2 (en) * 1999-09-22 2001-03-29 Corixa Corporation Methods for diagnosis and therapy of hematological and virus-associated malignancies

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1993017715A1 (en) * 1992-03-05 1993-09-16 Board Of Regents, The University Of Texas System Diagnostic and/or therapeutic agents, targeted to neovascular endothelial cells
WO2001000244A2 (en) * 1999-06-25 2001-01-04 Genentech, Inc. METHODS OF TREATMENT USING ANTI-ErbB ANTIBODY-MAYTANSINOID CONJUGATES
WO2001021192A2 (en) * 1999-09-22 2001-03-29 Corixa Corporation Methods for diagnosis and therapy of hematological and virus-associated malignancies

Non-Patent Citations (9)

* Cited by examiner, † Cited by third party
Title
CURR. MED. CHEM. (1996), 3(2), 87-100 *
DATABASE CA [online] CHEMICAL ABSTRACTS SERVICE, COLUMBUS, OHIO, US; MOKOTOFF, MICHAEL ET AL: "Targeting growth factor receptors with bispecific molecules", XP002177495, retrieved from STN Database accession no. 124:333195 *
DE SANTES, KENNETH ET AL: "Radiolabeled antibody targeting of the HER-2/neu oncoprotein", CANCER RES. (1992), 52(7), 1916-23, XP002177517 *
MANDLER, RAYA ET AL: "Immunoconjugates of geldanamycin and anti-HER2 monoclonal antibodies: antiproliferative activity on human breast carcinoma cell lines", J. NATL. CANCER INST. (2000), 92(19), 1573-1581, XP001024069 *
PARDRIDGE, WILLIAM M. ET AL: "Enhanced endocytosis in cultured human breast carcinoma cells and in vivo biodistribution in rats of a humanized monoclonal antibody after cationization of the protein", J. PHARMACOL. EXP. THER. (1998), 286(1), 548-554, XP001024036 *
PARK, J. W. ET AL: "Development of anti-p185HER2 immunoliposomes for cancer therapy", PROC. NATL. ACAD. SCI. U. S. A. (1995), 92(5), 1327-31, XP002177492 *
SCHMIDT, MATHIAS ET AL: "Synergistic Interaction between an Anti-p185HER-2 Pseudomonas Exotoxin Fusion Protein [scFv(FRP5)-ETA] and Ionizing Radiation for Inhibiting Growth of Ovarian Cancer Cells That Overexpress HER-2", GYNECOL. ONCOL. (2001), 80(2), 145-155, XP001024046 *
XING, RUYE ET AL: "Control of breast tumor cell growth using a targeted cysteine protease inhibitor", CANCER RES. (1998), 58(5), 904-909, XP002177494 *
XU, FENGJI ET AL: "Synergistic interaction between anti-p185HER-2 ricin A chain immunotoxins and radionuclide conjugates for inhibiting growth of ovarian and breast cancer cells that overexpress HER-2", CLIN. CANCER RES. (2000), 6(8), 3334-3341, XP001024035 *

Also Published As

Publication number Publication date
AU1490801A (en) 2001-05-30
EP1231944A2 (en) 2002-08-21
CA2391450A1 (en) 2001-05-25
WO2001036005A2 (en) 2001-05-25
JP2003523178A (en) 2003-08-05

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