EP2658579A4 - In vivo polynucleotide delivery conjugates having enzyme sensitive linkages - Google Patents

In vivo polynucleotide delivery conjugates having enzyme sensitive linkages

Info

Publication number
EP2658579A4
EP2658579A4 EP11853858.6A EP11853858A EP2658579A4 EP 2658579 A4 EP2658579 A4 EP 2658579A4 EP 11853858 A EP11853858 A EP 11853858A EP 2658579 A4 EP2658579 A4 EP 2658579A4
Authority
EP
European Patent Office
Prior art keywords
polynucleotide delivery
delivery conjugates
enzyme sensitive
sensitive linkages
vivo polynucleotide
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.)
Withdrawn
Application number
EP11853858.6A
Other languages
German (de)
French (fr)
Other versions
EP2658579A2 (en
Inventor
David B Rozema
David L Lewis
Darren H Wakefield
Eric A Kitas
Philipp Hadwiger
Jon A Wolff
Ingo Roehl
Peter Mohr
Torsten Hoffmann
Kerstin Jahn-Hofmann
Hans Martin Mueller
Guenther Ott
Andrei V Blokhin
Jeffrey C Carlson
Jonathan D Benson
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.)
Arrowhead Pharmaceuticals Inc
Original Assignee
Arrowhead Research Corp
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
Priority claimed from US13/336,028 external-priority patent/US8426554B2/en
Application filed by Arrowhead Research Corp filed Critical Arrowhead Research Corp
Publication of EP2658579A2 publication Critical patent/EP2658579A2/en
Publication of EP2658579A4 publication Critical patent/EP2658579A4/en
Withdrawn legal-status Critical Current

Links

Classifications

    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K5/00Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/04Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
    • C07K5/06Dipeptides
    • C07K5/06008Dipeptides with the first amino acid being neutral
    • C07K5/06017Dipeptides with the first amino acid being neutral and aliphatic
    • C07K5/06034Dipeptides with the first amino acid being neutral and aliphatic the side chain containing 2 to 4 carbon atoms
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07CACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C233/00Carboxylic acid amides
    • C07C233/01Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
    • C07C233/02Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having nitrogen atoms of carboxamide groups bound to hydrogen atoms or to carbon atoms of unsubstituted hydrocarbon radicals
    • C07C233/04Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having nitrogen atoms of carboxamide groups bound to hydrogen atoms or to carbon atoms of unsubstituted hydrocarbon radicals with carbon atoms of carboxamide groups bound to acyclic carbon atoms of an acyclic saturated carbon skeleton
    • C07C233/05Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having nitrogen atoms of carboxamide groups bound to hydrogen atoms or to carbon atoms of unsubstituted hydrocarbon radicals with carbon atoms of carboxamide groups bound to acyclic carbon atoms of an acyclic saturated carbon skeleton having the nitrogen atoms of the carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50Medicinal 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
    • A61K47/51Medicinal 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
    • A61K47/56Medicinal 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
    • A61K47/58Medicinal 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
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50Medicinal 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
    • A61K47/51Medicinal 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
    • A61K47/56Medicinal 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
    • A61K47/59Medicinal 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 otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes
    • A61K47/60Medicinal 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 otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K48/00Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/16Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07CACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C69/00Esters of carboxylic acids; Esters of carbonic or haloformic acids
    • C07C69/96Esters of carbonic or haloformic acids
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K5/00Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/04Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
    • C07K5/06Dipeptides
    • C07K5/06008Dipeptides with the first amino acid being neutral
    • C07K5/06078Dipeptides with the first amino acid being neutral and aromatic or cycloaliphatic
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K5/00Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/04Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
    • C07K5/06Dipeptides
    • C07K5/06104Dipeptides with the first amino acid being acidic
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K5/00Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/04Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
    • C07K5/06Dipeptides
    • C07K5/06104Dipeptides with the first amino acid being acidic
    • C07K5/06113Asp- or Asn-amino acid
    • CCHEMISTRY; METALLURGY
    • C08ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08GMACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
    • C08G63/00Macromolecular compounds obtained by reactions forming a carboxylic ester link in the main chain of the macromolecule
    • C08G63/91Polymers modified by chemical after-treatment
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09Recombinant DNA-technology
    • C12N15/87Introduction of foreign genetic material using processes not otherwise provided for, e.g. co-transformation
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09Recombinant DNA-technology
    • C12N15/11DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
    • C12N15/111General methods applicable to biologically active non-coding nucleic acids
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00Structure or type of the nucleic acid
    • C12N2310/10Type of nucleic acid
    • C12N2310/14Type of nucleic acid interfering N.A.
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00Structure or type of the nucleic acid
    • C12N2310/30Chemical structure
    • C12N2310/35Nature of the modification
    • C12N2310/351Conjugate
    • C12N2310/3513Protein; Peptide
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2320/00Applications; Uses
    • C12N2320/30Special therapeutic applications
    • C12N2320/32Special delivery means, e.g. tissue-specific
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2800/00Nucleic acids vectors
    • C12N2800/95Protection of vectors from inactivation by agents such as antibodies or enzymes, e.g. using polymers
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2810/00Vectors comprising a targeting moiety
    • C12N2810/10Vectors comprising a non-peptidic targeting moiety

Landscapes

  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Engineering & Computer Science (AREA)
  • Molecular Biology (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Biochemistry (AREA)
  • Biophysics (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Epidemiology (AREA)
  • Biotechnology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Biomedical Technology (AREA)
  • Wood Science & Technology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Engineering & Computer Science (AREA)
  • Zoology (AREA)
  • Plant Pathology (AREA)
  • Microbiology (AREA)
  • Physics & Mathematics (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Polymers & Plastics (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicinal Preparation (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Peptides Or Proteins (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
EP11853858.6A 2010-12-29 2011-12-28 In vivo polynucleotide delivery conjugates having enzyme sensitive linkages Withdrawn EP2658579A4 (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US201061427936P 2010-12-29 2010-12-29
US13/336,028 US8426554B2 (en) 2010-12-29 2011-12-23 In vivo polynucleotide delivery conjugates having enzyme sensitive linkages
PCT/US2011/067588 WO2012092373A2 (en) 2010-12-29 2011-12-28 In vivo polynucleotide delivery conjugates having enzyme sensitive linkages

Publications (2)

Publication Number Publication Date
EP2658579A2 EP2658579A2 (en) 2013-11-06
EP2658579A4 true EP2658579A4 (en) 2015-07-22

Family

ID=46383848

Family Applications (1)

Application Number Title Priority Date Filing Date
EP11853858.6A Withdrawn EP2658579A4 (en) 2010-12-29 2011-12-28 In vivo polynucleotide delivery conjugates having enzyme sensitive linkages

Country Status (15)

Country Link
EP (1) EP2658579A4 (en)
JP (1) JP5941926B2 (en)
KR (1) KR20130136494A (en)
CN (1) CN103491982B (en)
AU (1) AU2011352204B2 (en)
BR (1) BR112013014115A2 (en)
CA (1) CA2816041C (en)
CL (2) CL2013001876A1 (en)
MX (2) MX347298B (en)
NZ (1) NZ611656A (en)
PE (1) PE20140198A1 (en)
RU (1) RU2619453C2 (en)
SG (1) SG189942A1 (en)
WO (1) WO2012092373A2 (en)
ZA (1) ZA201302896B (en)

Families Citing this family (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR20150083920A (en) 2012-11-15 2015-07-20 로슈 이노베이션 센터 코펜하겐 에이/에스 Anti apob antisense conjugate compounds
WO2015021092A1 (en) * 2013-08-07 2015-02-12 Arrowhead Research Corporation Polyconjugates for delivery of rnai triggers to tumor cells in vivo
JOP20210043A1 (en) 2015-10-01 2017-06-16 Arrowhead Pharmaceuticals Inc Compositions and Methods for Inhibiting Gene Expression of LPA
MA45328A (en) * 2016-04-01 2019-02-06 Avidity Biosciences Llc NUCLEIC ACID-POLYPEPTIDE COMPOSITIONS AND USES THEREOF
PL3630742T3 (en) 2017-05-24 2024-04-08 Ramot At Tel-Aviv University Ltd. Chemiluminescent probes for imaging/detection of proteases
AU2018378812A1 (en) 2017-12-06 2020-07-09 Avidity Biosciences, Inc. Compositions and methods of treating muscle atrophy and myotonic dystrophy
JP2023501020A (en) * 2018-12-28 2023-01-18 サーナオミクス インコーポレイテッド Targeted delivery of therapeutic molecules
CA3172111A1 (en) 2020-03-19 2021-09-23 Barbora MALECOVA Compositions and methods of treating facioscapulohumeral muscular dystrophy
EP4285937A1 (en) * 2021-01-28 2023-12-06 Nanjing Chempion Biotechnology Co., Ltd. Conjugate and use thereof
KR20240024104A (en) * 2021-06-24 2024-02-23 가부시키가이샤 토호쿠 테크노 아치 fluorescent probe
US20230038188A1 (en) * 2021-07-27 2023-02-09 Andong National University Industry-Academic coorperation Foundation Pharmaceutical composition and health functional food for preventing, ameliorating or treating thrombosis containing extract of vespa velutina nigrithorax as active ingredient
CN113621003B (en) * 2021-09-10 2023-02-03 国科温州研究院(温州生物材料与工程研究所) Method for preparing organic molecule covalent modification functionalized nucleic acid material and application thereof
AU2022345098A1 (en) 2021-09-16 2024-04-04 Avidity Biosciences, Inc. Compositions and methods of treating facioscapulohumeral muscular dystrophy

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Publication number Priority date Publication date Assignee Title
US6180095B1 (en) * 1997-12-17 2001-01-30 Enzon, Inc. Polymeric prodrugs of amino- and hydroxyl-containing bioactive agents
WO2002083180A1 (en) * 2001-03-23 2002-10-24 Syntarga B.V. Elongated and multiple spacers in activatible prodrugs
US20030166601A1 (en) * 1999-12-30 2003-09-04 Woodle Martin C. Novel colloid synthetic vectors for gene therapy
US20070104719A1 (en) * 2000-02-24 2007-05-10 Genentech, Inc. Caspase Activated Prodrugs Therapy
US20080293800A1 (en) * 2005-11-10 2008-11-27 Medarex, Inc. Cytotoxic Compounds and Conjugates
WO2009141240A1 (en) * 2008-05-20 2009-11-26 Sigma-Tau Industrie Farmaceutiche Riunite S.P.A. Novel dual targeting antitumoural conjugates
WO2012083185A2 (en) * 2010-12-17 2012-06-21 Arrowhead Research Corporations Peptide-based in vivo sirna delivery system

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US6214345B1 (en) * 1993-05-14 2001-04-10 Bristol-Myers Squibb Co. Lysosomal enzyme-cleavable antitumor drug conjugates
US7091186B2 (en) * 2001-09-24 2006-08-15 Seattle Genetics, Inc. p-Amidobenzylethers in drug delivery agents
US7541330B2 (en) * 2004-06-15 2009-06-02 Kosan Biosciences Incorporated Conjugates with reduced adverse systemic effects
RU2430740C2 (en) * 2006-08-18 2011-10-10 Ф.Хоффманн-Ля Рош Аг Polyconjugates for polynucleotide introduction in vivo
JP5274461B2 (en) * 2006-08-18 2013-08-28 アローヘッド リサーチ コーポレイション Polyconjugates for in vivo delivery of polynucleotides
CA2916671C (en) * 2007-01-17 2018-01-09 Immunomedics, Inc. Polymeric carriers of therapeutic agents and recognition moieties for antibody-based targeting of disease sites

Patent Citations (7)

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Publication number Priority date Publication date Assignee Title
US6180095B1 (en) * 1997-12-17 2001-01-30 Enzon, Inc. Polymeric prodrugs of amino- and hydroxyl-containing bioactive agents
US20030166601A1 (en) * 1999-12-30 2003-09-04 Woodle Martin C. Novel colloid synthetic vectors for gene therapy
US20070104719A1 (en) * 2000-02-24 2007-05-10 Genentech, Inc. Caspase Activated Prodrugs Therapy
WO2002083180A1 (en) * 2001-03-23 2002-10-24 Syntarga B.V. Elongated and multiple spacers in activatible prodrugs
US20080293800A1 (en) * 2005-11-10 2008-11-27 Medarex, Inc. Cytotoxic Compounds and Conjugates
WO2009141240A1 (en) * 2008-05-20 2009-11-26 Sigma-Tau Industrie Farmaceutiche Riunite S.P.A. Novel dual targeting antitumoural conjugates
WO2012083185A2 (en) * 2010-12-17 2012-06-21 Arrowhead Research Corporations Peptide-based in vivo sirna delivery system

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Title
DUBOWCHIK G M ET AL: "Cathepsin B-labile dipeptide linkers for lysosomal release of doxorubicin from internalizing immunoconjugates: Model studies of enzymatic drug release and antigen-specific in vitro anticancer activity", BIOCONJUGATE CHEMISTRY, ACS, WASHINGTON, DC, US, vol. 13, no. 4, 1 January 2002 (2002-01-01), pages 855 - 869, XP002978657, ISSN: 1043-1802, DOI: 10.1021/BC025536J *

Also Published As

Publication number Publication date
MX2013007316A (en) 2013-07-29
RU2013117286A (en) 2015-03-10
EP2658579A2 (en) 2013-11-06
NZ611656A (en) 2014-10-31
CL2013001876A1 (en) 2014-04-11
JP2014505685A (en) 2014-03-06
CA2816041A1 (en) 2012-07-05
AU2011352204A1 (en) 2013-05-02
MX347298B (en) 2017-04-21
MX341118B (en) 2016-08-09
JP5941926B2 (en) 2016-06-29
RU2619453C2 (en) 2017-05-16
CN103491982A (en) 2014-01-01
CN103491982B (en) 2017-09-12
WO2012092373A3 (en) 2013-10-24
ZA201302896B (en) 2014-07-25
SG189942A1 (en) 2013-06-28
WO2012092373A2 (en) 2012-07-05
KR20130136494A (en) 2013-12-12
AU2011352204B2 (en) 2015-05-21
PE20140198A1 (en) 2014-02-21
BR112013014115A2 (en) 2019-09-24
CA2816041C (en) 2019-01-08
CL2015003580A1 (en) 2016-07-15

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