WO2003032913A3 - Methods and compositions for targeting proteins across the blood brain barrier - Google Patents

Methods and compositions for targeting proteins across the blood brain barrier Download PDF

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Publication number
WO2003032913A3
WO2003032913A3 PCT/US2002/032996 US0232996W WO03032913A3 WO 2003032913 A3 WO2003032913 A3 WO 2003032913A3 US 0232996 W US0232996 W US 0232996W WO 03032913 A3 WO03032913 A3 WO 03032913A3
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WO
WIPO (PCT)
Prior art keywords
compositions
methods
brain
igf
brain barrier
Prior art date
Application number
PCT/US2002/032996
Other languages
French (fr)
Other versions
WO2003032913A2 (en
WO2003032913A9 (en
Inventor
Jonathan H Lebowitz
Original Assignee
Symbiontics Inc
Jonathan H Lebowitz
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 US10/136,639 external-priority patent/US20030072761A1/en
Priority claimed from US10/136,841 external-priority patent/US7396811B2/en
Application filed by Symbiontics Inc, Jonathan H Lebowitz filed Critical Symbiontics Inc
Priority to AU2002347910A priority Critical patent/AU2002347910A1/en
Publication of WO2003032913A2 publication Critical patent/WO2003032913A2/en
Publication of WO2003032913A9 publication Critical patent/WO2003032913A9/en
Publication of WO2003032913A3 publication Critical patent/WO2003032913A3/en

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    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
    • C12N15/62—DNA sequences coding for fusion proteins
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/22—Hormones
    • A61K38/30—Insulin-like growth factors, i.e. somatomedins, e.g. IGF-1, IGF-2
    • 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
    • A61K47/64—Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent
    • A61K47/642—Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent the peptide or protein in the drug conjugate being a cytokine, e.g. IL2, chemokine, growth factors or interferons being the inactive part of the conjugate
    • 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
    • A61K47/64—Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent
    • A61K47/6425—Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent the peptide or protein in the drug conjugate being a receptor, e.g. CD4, a cell surface antigen, i.e. not a peptide ligand targeting the antigen, or a cell surface determinant, i.e. a part of the surface of a cell
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00—Drugs for disorders of the urinary system
    • A61P13/12—Drugs for disorders of the urinary system of the kidneys
    • 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
    • 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
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/575—Hormones
    • C07K14/65—Insulin-like growth factors, i.e. somatomedins, e.g. IGF-1, IGF-2
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C07K2319/01—Fusion polypeptide containing a localisation/targetting motif
    • C07K2319/02—Fusion polypeptide containing a localisation/targetting motif containing a signal sequence
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C07K2319/01—Fusion polypeptide containing a localisation/targetting motif
    • C07K2319/06—Fusion polypeptide containing a localisation/targetting motif containing a lysosomal/endosomal localisation signal
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C07K2319/20—Fusion polypeptide containing a tag with affinity for a non-protein ligand
    • C07K2319/21—Fusion polypeptide containing a tag with affinity for a non-protein ligand containing a His-tag
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C07K2319/50—Fusion polypeptide containing protease site
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C07K2319/61—Fusion polypeptide containing an enzyme fusion for detection (lacZ, luciferase)
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C07K2319/70—Fusion polypeptide containing domain for protein-protein interaction
    • C07K2319/74—Fusion polypeptide containing domain for protein-protein interaction containing a fusion for binding to a cell surface receptor
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C07K2319/70—Fusion polypeptide containing domain for protein-protein interaction
    • C07K2319/74—Fusion polypeptide containing domain for protein-protein interaction containing a fusion for binding to a cell surface receptor
    • C07K2319/75—Fusion polypeptide containing domain for protein-protein interaction containing a fusion for binding to a cell surface receptor containing a fusion for activation of a cell surface receptor, e.g. thrombopoeitin, NPY and other peptide hormones

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Chemical & Material Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • Medicinal Chemistry (AREA)
  • Molecular Biology (AREA)
  • Veterinary Medicine (AREA)
  • Animal Behavior & Ethology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Public Health (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Genetics & Genomics (AREA)
  • Zoology (AREA)
  • Biomedical Technology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Epidemiology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Urology & Nephrology (AREA)
  • Biophysics (AREA)
  • Immunology (AREA)
  • Wood Science & Technology (AREA)
  • Diabetes (AREA)
  • Endocrinology (AREA)
  • General Engineering & Computer Science (AREA)
  • Biotechnology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Biochemistry (AREA)
  • Vascular Medicine (AREA)
  • Neurosurgery (AREA)
  • Physics & Mathematics (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Toxicology (AREA)
  • Plant Pathology (AREA)
  • Microbiology (AREA)
  • Neurology (AREA)
  • Cardiology (AREA)

Abstract

Disclosed are methods and compositions for targeting therapeutic proteins to the brain. Methods and compositions of the invention involve associating an IGF moiety with a therapeutic protein in order to target the therapeutic protein to the brain. Soluble fusion proteins that include an IGF targeting moiety are transported to neural tissue in the brain from blood. Methods and compositions of the invention include therapeutic applications for treating lysosomal storage diseases. The invention also provides nucleic acids and cells for expressing IGF fusion proteins.
PCT/US2002/032996 2001-10-16 2002-10-16 Methods and compositions for targeting proteins across the blood brain barrier WO2003032913A2 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU2002347910A AU2002347910A1 (en) 2001-10-16 2002-10-16 Methods and compositions for targeting proteins across the blood brain barrier

Applications Claiming Priority (12)

Application Number Priority Date Filing Date Title
US32965001P 2001-10-16 2001-10-16
US60/329,650 2001-10-16
US10/136,639 2002-04-30
US10/136,639 US20030072761A1 (en) 2001-10-16 2002-04-30 Methods and compositions for targeting proteins across the blood brain barrier
US10/136,841 US7396811B2 (en) 2001-04-30 2002-04-30 Subcellular targeting of therapeutic proteins
US10/136,841 2002-04-30
US38445202P 2002-05-29 2002-05-29
US60/384,452 2002-05-29
US38601902P 2002-06-05 2002-06-05
US60/386,019 2002-06-05
US40881602P 2002-09-06 2002-09-06
US60/408,816 2002-09-06

Publications (3)

Publication Number Publication Date
WO2003032913A2 WO2003032913A2 (en) 2003-04-24
WO2003032913A9 WO2003032913A9 (en) 2004-04-29
WO2003032913A3 true WO2003032913A3 (en) 2004-08-12

Family

ID=27558195

Family Applications (2)

Application Number Title Priority Date Filing Date
PCT/US2002/032996 WO2003032913A2 (en) 2001-10-16 2002-10-16 Methods and compositions for targeting proteins across the blood brain barrier
PCT/US2002/032968 WO2003032727A1 (en) 2001-10-16 2002-10-16 Methods and compositions for targeting underglycosylated proteins across the blood brain barrier

Family Applications After (1)

Application Number Title Priority Date Filing Date
PCT/US2002/032968 WO2003032727A1 (en) 2001-10-16 2002-10-16 Methods and compositions for targeting underglycosylated proteins across the blood brain barrier

Country Status (6)

Country Link
EP (1) EP1446007A4 (en)
JP (2) JP2005506340A (en)
AU (3) AU2002347910A1 (en)
CA (1) CA2463473A1 (en)
IL (1) IL161352A0 (en)
WO (2) WO2003032913A2 (en)

Families Citing this family (28)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7560424B2 (en) 2001-04-30 2009-07-14 Zystor Therapeutics, Inc. Targeted therapeutic proteins
US7396811B2 (en) 2001-04-30 2008-07-08 Zystor Therapeutics, Inc. Subcellular targeting of therapeutic proteins
US7629309B2 (en) 2002-05-29 2009-12-08 Zystor Therapeutics, Inc. Targeted therapeutic proteins
US20030072761A1 (en) 2001-10-16 2003-04-17 Lebowitz Jonathan Methods and compositions for targeting proteins across the blood brain barrier
CA2463473A1 (en) * 2001-10-16 2003-04-24 Symbiontics Inc. Targeted therapeutic proteins
AU2003237314B2 (en) * 2002-05-29 2010-03-04 Biomarin Pharmaceutical Inc. Targeted therapeutic proteins
AU2005212435B2 (en) * 2004-02-10 2010-09-09 Biomarin Pharmaceutical Inc. Acid alpha-glucosidase and fragments thereof
CA3184105A1 (en) 2007-07-27 2009-02-05 Armagen Inc. Methods and compositions for increasing alpha-l-iduronidase activity in the cns
SI2234600T1 (en) * 2007-12-21 2014-12-31 F. Hoffmann-La Roche Ag Antibody formulation
AU2009244148B2 (en) 2008-05-07 2014-10-09 Biomarin Pharmaceutical Inc. Lysosomal targeting peptides and uses thereof
WO2010148253A2 (en) 2009-06-17 2010-12-23 Zystor Therapeutics, Inc. Formulations for lysosomal enzymes
RU2012154576A (en) 2010-06-25 2014-07-27 Шир Хьюман Дженетик Терапис, Инк. METHODS AND COMPOSITIONS FOR DELIVERY TO CNS HEPARAN-N-SULFATASE
RU2660348C2 (en) 2010-06-25 2018-07-05 Шир Хьюман Дженетик Терапис, Инк. Methods and compositions for cns delivery of iduronate-2-sulfatase
EP3103469B1 (en) 2010-06-25 2020-12-09 Shire Human Genetic Therapies, Inc. Cns delivery of therapeutic agents
KR20130043166A (en) * 2010-06-25 2013-04-29 샤이어 휴먼 지네틱 테라피즈 인크. Treatment of sanfilippo syndrome type b
PL2585104T3 (en) 2010-06-25 2020-01-31 Shire Human Genetic Therapies, Inc. Methods and compositions for cns delivery of arylsulfatase a
PT2588130T (en) * 2010-06-25 2016-11-25 Shire Human Genetic Therapies Cns delivery of therapeutic agents
CA2857567A1 (en) * 2011-12-01 2013-06-06 Angiochem Inc. Targeted lysosomal enzyme compounds
US20140377244A1 (en) 2011-12-23 2014-12-25 Shire Human Genetic Therapies, Inc. Stable formulations for cns delivery of arylsulfatase a
EP2885318A4 (en) 2012-08-14 2016-03-30 Angiochem Inc Peptide-dendrimer conjugates and uses thereof
DK2925776T3 (en) 2012-11-27 2018-09-03 Biomarin Pharm Inc TARGETED THERAPEUTIC LYSOSOMAL ENZYMUS FUSION PROTEINS AND APPLICATIONS THEREOF
CA2902289A1 (en) * 2013-03-15 2014-09-18 Glaxosmithkline Intellectual Property (No.2) Limited Low concentration antibody formulations
SG11201608025QA (en) 2014-04-01 2016-10-28 Swedish Orphan Biovitrum Ab Publ Modified sulfamidase and production thereof
JP6823055B2 (en) 2015-06-15 2021-01-27 アンジオケム インコーポレーテッド How to treat soft meningeal carcinomatosis
RU2751235C2 (en) 2016-02-24 2021-07-12 Байомарин Фармасьютикал Инк. Therapeutic targeted fusion proteins based on lysosomal enzymes, relevant compositions and their applications
EP3788064A1 (en) * 2018-04-30 2021-03-10 Amicus Therapeutics, Inc. Gene therapy constructs and methods of use
MX2021004188A (en) 2018-10-10 2021-09-08 Amicus Therapeutics Inc Disulfide bond stabilized polypeptide compositions and methods of use.
JP7458404B2 (en) 2018-12-20 2024-03-29 アーマジェン・インコーポレイテッド Purification of iduronic acid-2-sulfatase immunoglobulin fusion protein

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4801575A (en) * 1986-07-30 1989-01-31 The Regents Of The University Of California Chimeric peptides for neuropeptide delivery through the blood-brain barrier

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US5672683A (en) * 1989-09-07 1997-09-30 Alkermes, Inc. Transferrin neuropharmaceutical agent fusion protein
WO1991004014A1 (en) * 1989-09-21 1991-04-04 Synergen, Inc. Method for transporting compositions across the blood brain barrier
US6472140B1 (en) * 1997-09-05 2002-10-29 The General Hospital Corporation α-2- macroglobulin therapies and drug screening methods for Alzheimer's disease.
US7396811B2 (en) * 2001-04-30 2008-07-08 Zystor Therapeutics, Inc. Subcellular targeting of therapeutic proteins
CA2463473A1 (en) * 2001-10-16 2003-04-24 Symbiontics Inc. Targeted therapeutic proteins
AU2003237314B2 (en) * 2002-05-29 2010-03-04 Biomarin Pharmaceutical Inc. Targeted therapeutic proteins

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4801575A (en) * 1986-07-30 1989-01-31 The Regents Of The University Of California Chimeric peptides for neuropeptide delivery through the blood-brain barrier

Also Published As

Publication number Publication date
JP2005506340A (en) 2005-03-03
WO2003032913A2 (en) 2003-04-24
AU2010214643A1 (en) 2010-09-16
AU2002362930A2 (en) 2003-04-28
WO2003032727A1 (en) 2003-04-24
EP1446007A4 (en) 2005-12-07
WO2003032913A9 (en) 2004-04-29
AU2002347910A1 (en) 2003-04-28
EP1446007A1 (en) 2004-08-18
CA2463473A1 (en) 2003-04-24
IL161352A0 (en) 2004-09-27
JP2009203241A (en) 2009-09-10

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