CA2538748A1 - Cobalamin conjugates for anti-tumor therapy - Google Patents
Cobalamin conjugates for anti-tumor therapy Download PDFInfo
- Publication number
- CA2538748A1 CA2538748A1 CA002538748A CA2538748A CA2538748A1 CA 2538748 A1 CA2538748 A1 CA 2538748A1 CA 002538748 A CA002538748 A CA 002538748A CA 2538748 A CA2538748 A CA 2538748A CA 2538748 A1 CA2538748 A1 CA 2538748A1
- Authority
- CA
- Canada
- Prior art keywords
- cobalamin
- conjugate
- tumor drug
- spa
- drug
- 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.)
- Granted
Links
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
- 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
- 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
- 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.
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.
Claims (21)
1. An anti-tumor drug and cobalamin conjugate comprising:
a. cobalamin, or a derivative or analogue thereof;
b. a linker covalently bound to the 5'-OH moiety of cobalamin or cobalamin derivative;
c. an anti-tumor drug covalently bound to the linker thereby forming the conjugate, wherein the drug is cleavable from the linker and/or the linker is cleavable from the drug by an intracellular enzyme; the conjugate is adapted for transport across a cellular membrane after complexation with transcobalamin; the conjugate is cleavable by an intracellular enzyme; and the conjugate optionally possesses one or more protecting groups.
a. cobalamin, or a derivative or analogue thereof;
b. a linker covalently bound to the 5'-OH moiety of cobalamin or cobalamin derivative;
c. an anti-tumor drug covalently bound to the linker thereby forming the conjugate, wherein the drug is cleavable from the linker and/or the linker is cleavable from the drug by an intracellular enzyme; the conjugate is adapted for transport across a cellular membrane after complexation with transcobalamin; the conjugate is cleavable by an intracellular enzyme; and the conjugate optionally possesses one or more protecting groups.
2. The anti-tumor drug and cobalamin conjugate of claim 1, wherein cobalamin is selected from the group consisting of vitamin B12, cyanocobalamin, aquocobalamin, hydroxycobalamin, methylcobalamin, adenosylcobalamin, cyanocobalamin carbanalide, desdimethyl cobalamin, monoethylamide cobalamin, methylamide cobalamin, coenzyme B12, 5'-deoxyadenosylcobalamin, cobamamide derivatives, chlorocobalamin, sulfitocobalamin, nitrocobalamin, thiocyanatocobalamin, benzimidazole derivatives such as 5,6-dichlorobenzimidazole, 5-hydroxybenzimidazole, trimethylbenzimidazole, as well as adenosylcyanocobalamin ((Ade)GN-Cbl), cobalamin lactone, cobalamin lactam and the anilide, ethylamide, monocarboxylic, dicarboxylic and tricarboxylic acid derivatives of VB12, proprionamide derivatives of VB12, 5-o-methylbenzylcobalmin, and analogues thereof wherein the cobalt is replaced by another metal.
3. The anti-tumor drug and cobalamin conjugate of claim 1, wherein the anti-tumor drug is selected from the group consisting of doxorubicin and paclitaxel.
4. The anti-tumor drug and cobalamin conjugate of claim 1, wherein the linker is cleavable by way of an intracellular enzyme. selected from the group of enzyme classes consisting of cathepsin, endo enzyme, glycosidase, metalloprotease, ribozyme, protease, esterase, and amidase.
5. The anti-tumor drug and cobalamin conjugate of claim 1, wherein the conjugate possesses reduced systemic toxicity as compared to the corresponding free anti-tumor drug.
6. A method of treating a tumor related disorder or disease comprising the step of administering to a subject in need thereof a therapeutically effective amount of a conjugate according to claim 1.
7. An anti-tumor drug and cobalamin conjugate of the formula I:
VB-(SPa)n-CL-(SPb)m-DG
Formula I
wherein, a. CL is a linker that is cleavable from the VB, SPa, SPb and/or DG by way of an intracellular enzyme;
b. VB is cobalamin, or a derivative or analogue thereof, covalently bound to CL or SPa, if present, via the 5'-OH group of the ribose ring of VB;
c. SPa and SPb are optional spacers independently selected at each occurrence from the group consisting of a covalent bond, divalent functional group, or non-peptide residue, wherein SPa and SPb can be located on either side of CL; and d. DG is an anti-tumor drug possessing one or more functional groups by way which it is covalently bound to a spacer or CL;
e. wherein n and m are independently selected at each occurrence from 0, 1, or 2; and the conjugate optionally possesses one or more protecting groups.
VB-(SPa)n-CL-(SPb)m-DG
Formula I
wherein, a. CL is a linker that is cleavable from the VB, SPa, SPb and/or DG by way of an intracellular enzyme;
b. VB is cobalamin, or a derivative or analogue thereof, covalently bound to CL or SPa, if present, via the 5'-OH group of the ribose ring of VB;
c. SPa and SPb are optional spacers independently selected at each occurrence from the group consisting of a covalent bond, divalent functional group, or non-peptide residue, wherein SPa and SPb can be located on either side of CL; and d. DG is an anti-tumor drug possessing one or more functional groups by way which it is covalently bound to a spacer or CL;
e. wherein n and m are independently selected at each occurrence from 0, 1, or 2; and the conjugate optionally possesses one or more protecting groups.
8. The anti-tumor drug and cobalamin conjugate of claim 7, wherein the divalent functional group is selected from the group consisting of -NHNH-, -NH-, -O-, -S-, -SS-, -CH2-, -NHCO-, -CONH-, -CONHNHCO-, N N-, -N=CH-, -NHCH2-, -NHN=CH-, -NHNHCH2-, -SCH2-, -CH2S-, -NHCRNH- (R is =O, =S or NH), -COO-, and -OCO-.
9. The anti-tumor drug and cobalamin conjugate of claim 7, wherein cobalamin is selected from the group consisting of vitamin B12, cyanocobalamin, aquocobalamin, hydroxycobalamin, methylcobalamin, adenosylcobalamin, cyanocobalamin carbanalide, desdimethyl cobalamin, monoethylamide cobalamin, methylamide cobalamin, coenzyme B12, 5'-deoxyadenosylcobalamin, cobamamide derivatives, chlorocobalamin, sulfitocobalamin, nitrocobalamin, thiocyanatocobalamin, benzimidazole derivatives such as 5,6-dichlorobenzimidazole, 5-hydroxybenzimidazole, trimethylbenzimidazole, as well as adenosylcyanocobalamin ((Ade)CN-Cb1), cobalamin lactone, cobalamin lactam and the anilide, ethylamide, monocarboxylic, dicarboxylic and tricarboxylic acid derivatives of VB12, proprionamide derivatives of VB12, 5-o-methylbenzylcobalmin, and analogues thereof wherein the cobalt is replaced by another metal.
10. The anti-tumor drug and cobalamin conjugate of claim 7, wherein n and m are independently selected from 1, 2 or 3.
11. The anti-tumor drug and cobalamin conjugate of claim 7, wherein the non-peptide residue is selected from the group consisting of -NH-C6H4-CH2-O- and -NH(CH2)5C(=O)-.
12. The anti-tumor drug and cobalamin conjugate of claim 7, wherein the anti-tumor drug is selected from the group consisting of doxorubicin and paclitaxel.
13. The anti-tumor drug and cobalamin conjugate of claim 7 having the one of the following formulas:
a. VB-(SPa)p-CL-DG (Formula II);
b. VB-CL-(SPb)q-DG (Formula III);
c. VB-CL-DG (Formula IV);
d. VB-CL-(SPa)p-(SPb)q-DG (Formula V);
e. VB-(SPa)p-(SPb)q-CL-DG (Formula VI);
f. VB-(SPa)2(SPa)1-CL-(SPb)1(SPb)2-DG (Formula VII);
g. wherein p and q are independently selected from 1, 2 and 3.
a. VB-(SPa)p-CL-DG (Formula II);
b. VB-CL-(SPb)q-DG (Formula III);
c. VB-CL-DG (Formula IV);
d. VB-CL-(SPa)p-(SPb)q-DG (Formula V);
e. VB-(SPa)p-(SPb)q-CL-DG (Formula VI);
f. VB-(SPa)2(SPa)1-CL-(SPb)1(SPb)2-DG (Formula VII);
g. wherein p and q are independently selected from 1, 2 and 3.
14. The anti-tumor drug and cobalamin conjugate of claim 13, wherein:
a. (SPa)1 and (SPb)1 are each independently selected at each occurrence from a divalent functional group and a covalent bond; and b. (SPa)2 and (SPb)2 are each independently selected at each occurrence from a non-peptide residue.
a. (SPa)1 and (SPb)1 are each independently selected at each occurrence from a divalent functional group and a covalent bond; and b. (SPa)2 and (SPb)2 are each independently selected at each occurrence from a non-peptide residue.
15. The anti-tumor drug and cobalamin conjugate of claim 14, wherein:
a. (SPa)2 and (SPb)2 are each a divalent carbonyl; and b. (SPa)1 and (SPb)1 are each an -NH-, -S- and/or -O- containing non-peptide residue.
a. (SPa)2 and (SPb)2 are each a divalent carbonyl; and b. (SPa)1 and (SPb)1 are each an -NH-, -S- and/or -O- containing non-peptide residue.
16. The anti-tumor drug and cobalamin conjugate of claim 7, wherein the linker is cleavable by way of an intracellular enzyme selected from the group of enzyme classes consisting of cathepsin, endo enzyme, glycosidase, metalloprotease, ribozyme, protease, esterase, and amidase.
17. The anti-tumor drug and cobalamin conjugate of claim 7, wherein the conjugate possesses reduced systemic toxicity as compared to the corresponding free anti-tumor drug.
18. The anti-tumor drug and cobalamin conjugate of claim 17, wherein the conjugate possesses improved efficacy on a molar basis than the corresponding free anti-tumor drug.
19. The anti-tumor drug and cobalamin conjugate of claim 7, wherein the one or more functional groups are selected from the group consisting of a primary or secondary amine, hydroxyl, sulfhydryl, carboxyl, hydrazide, nitrile, aldehyde, and ketone.
20. The anti-tumor drug and cobalamin conjugate of claim 7, wherein the one or more functional groups comprises a derivatizable site on DG.
21. A method of treating a tumor related disorder or disease comprising the step of administering to a subject in need thereof a therapeutically effective amount of a conjugate according to claim 7.
Applications Claiming Priority (3)
| 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 | ||
| PCT/US2004/029879 WO2005025512A2 (en) | 2003-09-10 | 2004-09-10 | Cobalamin conjugates for anti-tumor therapy |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2538748A1 true CA2538748A1 (en) | 2005-03-24 |
| CA2538748C CA2538748C (en) | 2011-12-06 |
Family
ID=34226964
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2538748A Expired - Fee Related CA2538748C (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)
| 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 |
| CA2617907A1 (en) * | 2005-08-05 | 2007-02-15 | Syntarga B.V. | Triazole-containing releasable linkers and conjugates comprising the same |
| EP1976861A2 (en) * | 2005-11-29 | 2008-10-08 | The Scripps Research Institute | Inhibiting tumour cell invasion, metastasis and angiogenesis through targetting legumain |
| US20070225250A1 (en) * | 2006-01-26 | 2007-09-27 | 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 |
| US20080233135A1 (en) * | 2007-03-19 | 2008-09-25 | Gebhard John R | Cobalamin taxane bioconjugates |
| EA201070231A1 (en) * | 2007-08-09 | 2010-10-29 | Синтоникс Фармасьютикалз, Инк. | IMMUNOMODULATING PEPTIDES |
| PT2187965T (en) | 2007-08-17 | 2020-01-17 | Purdue Research Foundation | Psma binding ligand-linker conjugates and methods for using |
| WO2010011662A1 (en) * | 2008-07-21 | 2010-01-28 | Inflabloc Pharmaceuticals, Inc. | Taxane compounds for treating eye disease |
| WO2010014909A1 (en) * | 2008-08-01 | 2010-02-04 | Syntonix Pharmaceuticals, Inc. | Immunomodulatory peptides |
| DK3608330T3 (en) | 2008-12-16 | 2023-02-06 | Genzyme Corp | SYNTHETIC INTERMEDIATES FOR THE PREPARATION OF OLIGOSACCHARIDE-PROTEIN CONJUGATES |
| US20120053144A1 (en) * | 2009-01-27 | 2012-03-01 | Osiris Therapeutics, Inc. | 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 |
| JP6118914B2 (en) * | 2012-12-28 | 2017-04-19 | ターベダ セラピューティクス インコーポレイテッドＴａｒｖｅｄａ Ｔｈｅｒａｐｅｕｔｉｃｓ，Ｉｎｃ． | Controlled release solid polymer nanoparticles |
| EP3415489A1 (en) | 2013-10-18 | 2018-12-19 | Deutsches Krebsforschungszentrum | Labeled inhibitors of prostate specific membrane antigen (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 |
Family Cites Families (32)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CH385873A (en) | 1959-04-06 | 1964-12-31 | Merck & Co Inc | Process for the preparation of amino acid hydroxo-cobalamin |
| US3130189A (en) * | 1959-04-06 | 1964-04-21 | Merck & Co Inc | Hydroxocobalamin-glutathione |
| 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 |
| SG52537A1 (en) * | 1990-10-17 | 1998-09-28 | Amgen Inc | Methods and compositions for the treatment of cell proliferation disorders |
| US6214345B1 (en) * | 1993-05-14 | 2001-04-10 | Bristol-Myers Squibb Co. | Lysosomal enzyme-cleavable antitumor drug conjugates |
| SG50426A1 (en) * | 1993-05-20 | 1998-07-20 | Biotech Australia Pty Ltd | Lhrh antagonists |
| 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 |
| CA2187346C (en) * | 1994-04-08 | 2010-06-29 | A. Charles Morgan, Jr. | Receptor modulating agents and methods relating thereto |
| US5840880A (en) * | 1994-04-08 | 1998-11-24 | Receptagen Corporation | Receptor modulating agents |
| US5869465A (en) * | 1994-04-08 | 1999-02-09 | Receptagen Corporation | Methods of receptor modulation and uses therefor |
| US5739287A (en) * | 1994-04-08 | 1998-04-14 | University Of Washington | Biotinylated cobalamins |
| US5574018A (en) * | 1994-07-29 | 1996-11-12 | Amgen Inc. | Conjugates of vitamin B12 and proteins |
| WO1998008859A1 (en) * | 1996-08-27 | 1998-03-05 | University Of Utah Research Foundation | Bioconjugates and delivery of bioactive agents |
| WO1998013059A1 (en) | 1996-09-27 | 1998-04-02 | 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 |
| JP2002542207A (en) | 1999-04-16 | 2002-12-10 | メイオウ・フアウンデーシヨン・フオー・メデイカル・エジユケイシヨン・アンド・リサーチ | Cobalamin conjugates useful as antitumor agents |
| WO2001028595A1 (en) | 1999-10-15 | 2001-04-26 | Mayo Foundation For Medical Education And Research | Cobalamin conjugates useful as imaging and therapeutic agents |
| JP2003512338A (en) * | 1999-10-15 | 2003-04-02 | メイオウ・フアウンデーシヨン・フオー・メデイカル・エジユケイシヨン・アンド・リサーチ | Cobalamin conjugates useful as contrast agents and antitumor agents |
| US6797521B2 (en) * | 1999-10-26 | 2004-09-28 | University Of Utah Research Foundation | Fluorescent cobalamins and uses thereof |
| CA2387503C (en) | 1999-10-26 | 2010-02-09 | University Of Utah Research Foundation | Fluorescent cobalamins 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 |
| AU6972901A (en) * | 2000-05-31 | 2001-12-11 | Mayo Foundation | Cobalamin compounds useful as cardiovascular agents and as imaging agents |
| EP1334114A2 (en) * | 2000-10-25 | 2003-08-13 | Mayo Foundation For Medical Education And Research | Transcobalamin binding conjugates useful for treating abnormal cellular proliferation |
| CA2441146C (en) | 2001-03-16 | 2011-08-09 | University Of Utah Research Foundation | Fluorescent cobalamins and uses thereof |
| AU2002362312A1 (en) | 2001-09-17 | 2003-04-01 | Mayo Foundation For Medical Education And Research | Cobalamin mediated delivery of nucleic acids, analogs and derivatives thereof |
| CA2461705A1 (en) * | 2001-09-28 | 2003-04-03 | Mayo Foundation For Medical Education And Research | Coadministration of transport protein with conjugated cobalamin to deliver agents |
-
2003
- 2003-09-10 US US10/659,501 patent/US7232805B2/en not_active Expired - Fee Related
-
2004
- 2004-09-10 EP EP04783919A patent/EP1672978A4/en not_active Withdrawn
- 2004-09-10 KR KR1020067004844A patent/KR20070019942A/en not_active Application Discontinuation
- 2004-09-10 AU AU2004272105A patent/AU2004272105B2/en not_active Ceased
- 2004-09-10 WO PCT/US2004/029879 patent/WO2005025512A2/en active Search and Examination
- 2004-09-10 JP JP2006526379A patent/JP2007505144A/en active Pending
- 2004-09-10 CA CA2538748A patent/CA2538748C/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| EP1672978A2 (en) | 2006-06-28 |
| US20050054607A1 (en) | 2005-03-10 |
| WO2005025512A3 (en) | 2005-07-28 |
| AU2004272105A1 (en) | 2005-03-24 |
| WO2005025512A2 (en) | 2005-03-24 |
| EP1672978A4 (en) | 2006-12-20 |
| AU2004272105B2 (en) | 2011-03-10 |
| JP2007505144A (en) | 2007-03-08 |
| CA2538748C (en) | 2011-12-06 |
| KR20070019942A (en) | 2007-02-16 |
| US7232805B2 (en) | 2007-06-19 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CA2538748A1 (en) | Cobalamin conjugates for anti-tumor therapy | |
| Chytil et al. | HPMA copolymer–drug conjugates with controlled tumor‐specific drug release | |
| Reddy et al. | Novel approaches to deliver gemcitabine to cancers | |
| Deshmukh et al. | A series of α-amino acid ester prodrugs of camptothecin: In vitro hydrolysis and A549 human lung carcinoma cell cytotoxicity | |
| WO2001062300A3 (en) | Caspase activated prodrugs therapy | |
| CA2264592A1 (en) | Bioconjugates and delivery of bioactive agents | |
| NZ291368A (en) | A compound comprising a marker or a therapeutic agent linked to a ligand containing amino acids wherein the marker or agent is cleaved from the ligand to permit entry into the cell of the marker or agent, medicaments for treating tumours; diagnostic devices | |
| US20120015900A1 (en) | Cobalamin Taxane Bioconjugates | |
| Zou et al. | Effectiveness of water soluble poly (L-glutamic acid)-camptothecin conjugate against resistant human lung cancer xenografted in nude mice | |
| Jain et al. | Advances in oral delivery of anti-cancer prodrugs | |
| Tietze et al. | Highly selective compounds for the antibody-directed enzyme prodrug therapy of cancer | |
| Manickam et al. | Design, synthesis and anticancer activity of 2-amidomethoxy-1, 4-naphthoquinones and its conjugates with Biotin/polyamine | |
| Adiyala et al. | Development of pyrrolo [2, 1-c][1, 4] benzodiazepine β-glucoside prodrugs for selective therapy of cancer | |
| Vasey et al. | 929 Clinical phase I trial of PK1 (HPMA co-polymer doxorubicin) | |
| US20220288007A1 (en) | Platinum Complex Anti-Neoplastic Agents Comprising a Cannabinoid Ligand | |
| WO2000062808A8 (en) | Cobalamin conjugates useful as antitumor agents | |
| Soyez et al. | Macromolecular derivatives of N, N-di-(2-chloroethyl)-4-phenylene diamine mustard. 2. In vitro cytotoxicity and in vivo anticancer efficacy | |
| US20030195161A1 (en) | Composition comprising camptothecin or a camptothecin derivative and a topoisomerase II inhibitor for the treatment of cancer | |
| US20120053144A1 (en) | Cobalamin Taxane Bioconjugates For Treating Eye Disease | |
| Bhumkar et al. | STUDIES OF PRODRUG APPROACH IN ANTICANCER DRUGS | |
| Schnell et al. | 930 A clinical phase I study of an anti-CD25-deglycosylated ricin A-chain immunotoxin (RFT5-SMPT-DGA) in patients with refractory Hodgkin's disease | |
| Hynes et al. | Effects of 5, 8-dideazaisopteroylglutamate (IAHQ) on L1210 leukemia in mice when given alone and in combination with methotrexate, probenecid, or verapamil | |
| O’Dwyer et al. | 928 Phase I trial of the topoisomerase I inhibitor GG211 as a 72-hour infusion | |
| Eckardt et al. | 927 A phase I and bioavailability study of oral topotecan | |
| US20100016256A1 (en) | Taxane Compounds for Treating Eye Disease |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| MKLA | Lapsed |
Effective date: 20140910 |