WO2005025512A3 - Cobalamin conjugates for anti-tumor therapy - Google Patents

Cobalamin conjugates for anti-tumor therapy Download PDF

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Publication number
WO2005025512A3
WO2005025512A3 PCT/US2004/029879 US2004029879W WO2005025512A3 WO 2005025512 A3 WO2005025512 A3 WO 2005025512A3 US 2004029879 W US2004029879 W US 2004029879W WO 2005025512 A3 WO2005025512 A3 WO 2005025512A3
Authority
WO
WIPO (PCT)
Prior art keywords
conjugate
drug
cobalamin
cleavable linker
cell
Prior art date
Application number
PCT/US2004/029879
Other languages
French (fr)
Other versions
WO2005025512A2 (en
Inventor
Ned M Weinshenker
Frederick G West
Barbara A Araneo
Weiping Li
Original Assignee
Manticore Pharmaceuticals Inc
Ned M Weinshenker
Frederick G West
Barbara A Araneo
Weiping Li
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 Manticore Pharmaceuticals Inc, Ned M Weinshenker, Frederick G West, Barbara A Araneo, Weiping Li filed Critical Manticore Pharmaceuticals Inc
Priority to CA2538748A priority Critical patent/CA2538748C/en
Priority to AU2004272105A priority patent/AU2004272105B2/en
Priority to JP2006526379A priority patent/JP2007505144A/en
Priority to EP04783919A priority patent/EP1672978A4/en
Publication of WO2005025512A2 publication Critical patent/WO2005025512A2/en
Publication of WO2005025512A3 publication Critical patent/WO2005025512A3/en

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Classifications

    • 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
    • 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
    • A61K47/55—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 also a pharmacologically or therapeutically active agent, i.e. the entire conjugate being a codrug, i.e. a dimer, oligomer or polymer of pharmacologically or therapeutically active compounds
    • A61K47/551—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 also a pharmacologically or therapeutically active agent, i.e. the entire conjugate being a codrug, i.e. a dimer, oligomer or polymer of pharmacologically or therapeutically active compounds one of the codrug's components being a vitamin, e.g. niacinamide, vitamin B3, cobalamin, vitamin B12, folate, vitamin A or retinoic acid
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents

Abstract

The present invention provides a cobalamin-drug conjugate suitable for the treatment of tumor related diseases. Cobalamin is indirectly covalently bound to an antitumor drug via a cleavable linker and one or more optional spacers. Cobalanin is covalently bound to a first spacer or the cleavable linker via the 5'-OH of the cobalamin ribose ring. The drug is bound to a second spacer of the cleavable linker via an existing or added functional group on the drug. After administration, the conjugate forms a complex with transcobalamin (any of its isoforms). The complex then binds to a receptor on a cell membrane and is taken up into the cell. Once in the cell, an intracellular enzyme cleaves the conjugate thereby releasing the drug. Depending upon the structure of the conjugate, a particular class or type of intracellular enzyme affects the cleavage. Due to the high demand for cobalamin in growing cells, tumor cells typically take up a higher percentage of the conjugate than do normal non-growing cells. The conjugate of the invention advantageously provides a reduced systemic toxicity and enhanced efficacy as compared to a corresponding free drug.
PCT/US2004/029879 2003-09-10 2004-09-10 Cobalamin conjugates for anti-tumor therapy WO2005025512A2 (en)

Priority Applications (4)

Application Number Priority Date Filing Date Title
CA2538748A CA2538748C (en) 2003-09-10 2004-09-10 Cobalamin conjugates for anti-tumor therapy
AU2004272105A AU2004272105B2 (en) 2003-09-10 2004-09-10 Cobalamin conjugates for anti-tumor therapy
JP2006526379A JP2007505144A (en) 2003-09-10 2004-09-10 Cobalamin conjugates for antitumor therapy
EP04783919A EP1672978A4 (en) 2003-09-10 2004-09-10 Cobalamin conjugates for anti-tumor therapy

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US10/659,501 US7232805B2 (en) 2003-09-10 2003-09-10 Cobalamin conjugates for anti-tumor therapy
US10/659,501 2003-09-10

Publications (2)

Publication Number Publication Date
WO2005025512A2 WO2005025512A2 (en) 2005-03-24
WO2005025512A3 true WO2005025512A3 (en) 2005-07-28

Family

ID=34226964

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2004/029879 WO2005025512A2 (en) 2003-09-10 2004-09-10 Cobalamin conjugates for anti-tumor therapy

Country Status (7)

Country Link
US (1) US7232805B2 (en)
EP (1) EP1672978A4 (en)
JP (1) JP2007505144A (en)
KR (1) KR20070019942A (en)
AU (1) AU2004272105B2 (en)
CA (1) CA2538748C (en)
WO (1) WO2005025512A2 (en)

Families Citing this family (22)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20040047917A1 (en) * 2002-09-06 2004-03-11 Stephen Wilson Drug delivery and targeting with vitamin B12 conjugates
US20100113328A1 (en) * 2003-05-29 2010-05-06 The Scripps Research Institute Targeted delivery to legumain-expressing cells
EP1909846B1 (en) * 2005-08-05 2018-12-26 Syntarga B.V. Triazole-containing releasable linkers, conjugates comprising the same and processes for their preparation
EP1976861A2 (en) * 2005-11-29 2008-10-08 The Scripps Research Institute Inhibiting tumour cell invasion, metastasis and angiogenesis through targetting legumain
WO2007087631A2 (en) * 2006-01-26 2007-08-02 Bebaas, Inc. Cobalamin compositions for the treatment of cancer
TW200745163A (en) 2006-02-17 2007-12-16 Syntonix Pharmaceuticals Inc Peptides that block the binding of IgG to FcRn
WO2008115805A2 (en) * 2007-03-19 2008-09-25 Inflabloc Pharmaceuticals, Inc. Cobalamin taxane bioconjugates
EA201070231A1 (en) * 2007-08-09 2010-10-29 Синтоникс Фармасьютикалз, Инк. IMMUNOMODULATING PEPTIDES
HUE047200T2 (en) 2007-08-17 2020-04-28 Purdue Research Foundation Psma binding ligand-linker conjugates and methods for using
CA2731503A1 (en) * 2008-07-21 2010-01-28 Osiris Therapeutics, Inc. Taxane compounds for treating eye disease
US20100048488A1 (en) * 2008-08-01 2010-02-25 Syntonix Pharmaceuticals, Inc. Immunomodulatory peptides
EP3608330B1 (en) 2008-12-16 2022-11-09 Genzyme Corporation Synthetic intermediates for preparing oligosaccharide-protein conjugates
WO2010088287A1 (en) * 2009-01-27 2010-08-05 Gebhard John R Cobalamin taxane bioconjugates for treating eye disease
US9951324B2 (en) 2010-02-25 2018-04-24 Purdue Research Foundation PSMA binding ligand-linker conjugates and methods for using
CN102199180B (en) * 2011-04-12 2014-07-09 连云港杰瑞药业有限公司 Preparation method of capectabine
US20150335761A1 (en) * 2012-02-16 2015-11-26 Raymond Firestone Compositions and methods for contraception
JP6892218B2 (en) 2012-11-15 2021-06-23 エンドサイト・インコーポレイテッドＥｎｄｏｃｙｔｅ， Ｉｎｃ． How to treat diseases caused by drug delivery conjugates and PSMA-expressing cells
US20140187501A1 (en) * 2012-12-28 2014-07-03 Blend Therapeutics, Inc. Targeted Conjugates Encapsulated in Particles and Formulations Thereof
PE20160678A1 (en) 2013-10-18 2016-08-06 Deutsches Krebsforsch MARKED MEMBRANE-SPECIFIC PROSTATIC ANTIGEN INHIBITORS (PSMA), THEIR USE AS IMAGING AGENTS AND PHARMACEUTICAL AGENTS FOR THE TREATMENT OF PROSTATE CANCER
US10188759B2 (en) 2015-01-07 2019-01-29 Endocyte, Inc. Conjugates for imaging
CN108371709A (en) * 2018-03-29 2018-08-07 苟春虎 Lycium ruthenicum tumor recovering gene enzyme
US11155821B2 (en) 2018-07-31 2021-10-26 The Regents Of The University Of Colorado, A Body Corporate Compositions and methods for tagging ribonucleic acids

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6315978B1 (en) * 1996-08-27 2001-11-13 University Of Utah, Research Foundation Bioconjugates and delivery of bioactive agents

Family Cites Families (31)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3130189A (en) 1959-04-06 1964-04-21 Merck & Co Inc Hydroxocobalamin-glutathione
CH385873A (en) 1959-04-06 1964-12-31 Merck & Co Inc Process for the preparation of amino acid hydroxo-cobalamin
NZ217821A (en) 1985-10-10 1989-07-27 Biotech Australia Pty Ltd Oral delivery system; complex of active agent and vitamin b12 or analogue thereof
US5807832A (en) 1987-06-09 1998-09-15 Biotech Australia Pty Limited Oral delivery of biologically active substances bound to vitamin B12
US5405839A (en) 1989-02-28 1995-04-11 Teijin Limited Vitamin B12 derivative, preparation process thereof, and use thereof
ES2128348T3 (en) * 1990-10-17 1999-05-16 Amgen Inc OBTAINING COMPOSITIONS FOR THE TREATMENT OF ALTERATIONS OF CELL PROLIFERATION.
US6214345B1 (en) 1993-05-14 2001-04-10 Bristol-Myers Squibb Co. Lysosomal enzyme-cleavable antitumor drug conjugates
JPH08510260A (en) 1993-05-20 1996-10-29 バイオテック・オーストラリア・プロプライエタリー・リミテッド LHRH antagonist
US5449720A (en) 1993-05-24 1995-09-12 Biotech Australia Pty Limited Amplification of the VB12 uptake system using polymers
US5548064A (en) 1993-05-24 1996-08-20 Biotech Australia Pty Limited Vitamin B12 conjugates with EPO, analogues thereof and pharmaceutical compositions
US5739287A (en) 1994-04-08 1998-04-14 University Of Washington Biotinylated cobalamins
US5840880A (en) 1994-04-08 1998-11-24 Receptagen Corporation Receptor modulating agents
KR100361075B1 (en) 1994-04-08 2003-04-10 리셉타겐 코포레이션 Receptor Modulators and Associated Methods
US5869465A (en) 1994-04-08 1999-02-09 Receptagen Corporation Methods of receptor modulation and uses therefor
US5574018A (en) * 1994-07-29 1996-11-12 Amgen Inc. Conjugates of vitamin B12 and proteins
AU739028B2 (en) 1996-09-27 2001-10-04 Bristol-Myers Squibb Company Hydrolyzable prodrugs for delivery of anticancer drugs to metastatic cells
US20020155999A1 (en) 1998-04-30 2002-10-24 Han In Suk Method of using a porphyrin-like molecule conjugated with an anti-cancer drug for the treatment of cancer
AUPP405098A0 (en) 1998-06-12 1998-07-02 Access Pharmaceuticals Australia Pty Limited Novel methods of preparation of vitamin b12 derivatives suitable for conjugation to pharmaceuticals
FR2787029A1 (en) 1998-12-09 2000-06-16 Biovector Therapeutics USE IN A PHARMACEUTICAL COMPOSITION FOR NASAL ADMINISTRATION OF VITAMIN B12 FOR THE DELIVERY OF ACTIVE AGENTS TO THE CENTRAL NERVOUS SYSTEM
GB9906808D0 (en) 1999-03-24 1999-05-19 Kilgowan Limited Formulation for treatment of pain
WO2000062808A2 (en) 1999-04-16 2000-10-26 Mayo Foundation For Medical Education And Research Cobalamin conjugates useful as antitumor agents
EP1239887A1 (en) 1999-10-15 2002-09-18 Mayo Foundation For Medical Education And Research Cobalamin conjugates useful as imaging and therapeutic agents
EP1231942A1 (en) * 1999-10-15 2002-08-21 Mayo Foundation For Medical Education And Research Cobalamin conjugates useful as imaging agents and as antitumor agents
US6797521B2 (en) 1999-10-26 2004-09-28 University Of Utah Research Foundation Fluorescent cobalamins and uses thereof
JP5350570B2 (en) 1999-10-26 2013-11-27 ユニバーシティ・オブ・ユタ・リサーチ・ファウンデイション Fluorescent cobalamin and uses thereof
AU2001272935A1 (en) 2000-05-31 2001-12-11 Mayo Foundation For Medical Education And Research Cobalamin compounds useful as antibiotic agents and as imaging agents
WO2001092283A2 (en) 2000-05-31 2001-12-06 Mayo Foundation For Medical Education And Research Cobalamin compounds useful as cardiovascular agents and as imaging agents
AU2002243438A1 (en) 2000-10-25 2002-07-24 Mayo Foundation For Medical Education And Research Transcobalamin binding conjugates useful for treating abnormal cellular proliferation
WO2002074171A1 (en) 2001-03-16 2002-09-26 University Of Utah Research Foundation Fluorescent cobalamins and uses thereof
WO2003025139A2 (en) 2001-09-17 2003-03-27 Mayo Foundation For Medical Education And Research Cobalamin mediated delivery of nucleic acids, analogs and derivatives thereof
EP1435973A4 (en) * 2001-09-28 2007-05-02 Mayo Foundation Coadministration of transport protein with conjugated cobalamin to deliver agents

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6315978B1 (en) * 1996-08-27 2001-11-13 University Of Utah, Research Foundation Bioconjugates and delivery of bioactive agents

Also Published As

Publication number Publication date
EP1672978A4 (en) 2006-12-20
US7232805B2 (en) 2007-06-19
AU2004272105B2 (en) 2011-03-10
US20050054607A1 (en) 2005-03-10
AU2004272105A1 (en) 2005-03-24
EP1672978A2 (en) 2006-06-28
KR20070019942A (en) 2007-02-16
CA2538748C (en) 2011-12-06
WO2005025512A2 (en) 2005-03-24
JP2007505144A (en) 2007-03-08
CA2538748A1 (en) 2005-03-24

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