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WO1999030157A9 - Neuropilines et leur utilisation a des fins de diagnostic et de pronostic du cancer - Google Patents

Neuropilines et leur utilisation a des fins de diagnostic et de pronostic du cancer

Info

Publication number
WO1999030157A9
WO1999030157A9 PCT/US1998/026127 US9826127W WO9930157A9 WO 1999030157 A9 WO1999030157 A9 WO 1999030157A9 US 9826127 W US9826127 W US 9826127W WO 9930157 A9 WO9930157 A9 WO 9930157A9
Authority
WO
WIPO (PCT)
Prior art keywords
vegf
cells
kdr
receptor
tumor
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.)
Ceased
Application number
PCT/US1998/026127
Other languages
English (en)
Other versions
WO1999030157A3 (fr
WO1999030157A2 (fr
Inventor
Michael Klagsbrun
Shay Soker
Hua-Quan Miao
Seiji Takashima
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.)
Boston Childrens Hospital
Original Assignee
Boston Childrens Hospital
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 Boston Childrens Hospital filed Critical Boston Childrens Hospital
Priority to AU18108/99A priority Critical patent/AU1810899A/en
Publication of WO1999030157A2 publication Critical patent/WO1999030157A2/fr
Publication of WO1999030157A3 publication Critical patent/WO1999030157A3/fr
Publication of WO1999030157A9 publication Critical patent/WO1999030157A9/fr
Priority to US09/583,638 priority patent/US6635421B1/en
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • 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
    • C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
    • C07K14/71—Receptors; Cell surface antigens; Cell surface determinants for growth factors; for growth regulators
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • 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
    • A61P35/00—Antineoplastic agents
    • A61P35/04—Antineoplastic agents specific for metastasis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K48/00—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy

Definitions

  • FIGS 2 A and 2B show isolation of VEGF) 65 R cDNA by Expression Cloning. Photomicrographs (dark field illumination) of COS 7 cells binding 125 I-VEGF ⁇ 65 . 12:> I- VEGF 165 was bound to transfected COS 7 cells which were then washed, fixed, and overlayed with photographic emulsion that was developed as described in the example, infra.
  • Figure 6 shows a Northern Blot Analysis of VEGF ⁇ 6 sR NP-l and KDR mRNA in Adult Human Tissues.
  • a pre -made Northern blot membrane containing multiple samples of human mRNA (Clonetech) was probed with j2 P-labeled VEGF ⁇ R/NP-l cDNA (top) as described m Fig 5, and then stripped and reprobed with P-labeled KDR cDNA (bottom)
  • Figures 7A and 7B show a Scatchard Analysis of VEGF ⁇ 6 s binding to
  • VEGF receptors VEGFi 6 R NP-l and NP-2
  • VEGFi 6 R NP-l and NP-2 VEGF 16 5R/NP-I and NP-2 but any neuropilin or VEGFR, where the constituents share at least about 85%o homology with either of the above VEGF] 6 -,R/NP-1 and NP-2 can be used More preferably, such constituent shares at least 90% homology Still more preferably, each constituent shares at least 95% homology
  • isolated means that the polypeptide is removed from its original environment (e.g., the native VEGF molecule).
  • a naturally-occurring polynucleotides or polypeptides present in a living animal is not isolated, but the same polynucleotides or DNA or polypeptides, separated from some or all of the coexisting materials in the natural system, is isolated.
  • Such polynucleotides could be part of a vector and/or such polynucleotides or polypeptides could be part of a composition, and still be isolated in that such vector or composition is not part of its natural environment.
  • any suitable system can be used. The general nature of suitable vectors, expression vectors and constructions therefor will be apparent to those skilled in the art.
  • polypeptides and proteins may be isolated from the fermentation or cell culture and purified using any of a variety of conventional methods including liquid chromatography such as normal or reversed phase, using HPLC, FPLC and the like, affinity chromatography (such as with inorganic ligands or monoclonal antibodies), size exclusion chromatography, immobilized metal chelate chromatography, gel electrophoresis, and the like.
  • VEGF antagonist in solid form, especially as a lyophilized powder.
  • Lyophilized formulations typically contain stabilizing and bulking agents, for example human serum albumin, sucrose, mannitol, and the like. A thorough discussion of pharmaceutically acceptable excipients is available in Remington's Pharmaceutical Sciences (Mack Pub. Co.).
  • cDNA Complementary DNA
  • EcoRl adaptors EcoRl adaptors
  • size-fractionated on a 5- 20% potassium acetate gradient DNA fragments larger than 2kb were ligated to an eukaryotic expression plasmid, pcDNA3 1
  • the plasmid library was transfected into E coli to yield a primary library of approximately 1 x 10 7 individual clones
  • a portion of the transformed bacteria was divided into 240 pools, each representing approximately 3 x 10 3 individual clones DNA prepared from each pool was used to transfect COS-7 cells seeded in 12 well dishes, using the Lipofectin reagent according to the manufacturer's instructions
  • the cells were incubated on ice for 2 h with 123 I-VEGF ⁇ 6 5 (10 ng/ml) in the presence of 1 ⁇ g/ml heparin, washed and fixed with 4% paraformaldehyde in PBS ' "
  • Neuropilin- 1 is an isoform-specific VEGF i 6 5 receptor
  • VEGF1 6 5R Soker et al , J Biol Chem 271, 5761-5767 (1996)
  • NP- 1 human neuropilin- 1
  • NP-1 human neuropilin- 1
  • the evidence that VEGF, 6 ,R is identical to NP-1 and that NP-1 serves as a receptor for VEGF 1 5 is as follows 1) purification of VEGF 16 5R protein from human MDA-MB-231 (231) cells using VEGF affinity, yielded a 130-140 kDa doublet upon SDS-PAGE and silver stain N-terminal
  • VEGF ⁇ 65 R/NP-l and KDR When VEGF ⁇ 65 R/NP-l and KDR are co-expressed, the binding of I25 I- VEGF 165 to KDR is enhanced by about 4-fold compared to cells expressing KDR alone.
  • the enhanced binding can be demonstrated in stable clones co-expressing VEGF 165 R/NP-I and KDR (PAE/KDR/NP-l cells), and also in PAE/KDR cells transfected transiently with VEGF 165 R/NP-I cDNA where clonal selection does not take place.

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Organic Chemistry (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Immunology (AREA)
  • Rheumatology (AREA)
  • Pain & Pain Management (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Cardiology (AREA)
  • Oncology (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Cell Biology (AREA)
  • Toxicology (AREA)
  • Zoology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Biochemistry (AREA)
  • Biophysics (AREA)
  • Genetics & Genomics (AREA)
  • Molecular Biology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Peptides Or Proteins (AREA)
  • Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

L'invention porte sur des récepteurs du facteur de croissance de l'endothélium vasculaire (VEGFR), et des neuropilines telles que les VEGF165R/NP-1 et NP-2 qui sont associées au potentiel métastatique des cellules malignes, et sur leur utilisation pour diagnostiquer ou pronostiquer le cancer. Les neuropilines VEGF165R/NP-1 et NP-2 sont préférées, mais toute neuropiline ou tout VEGFR dont les constituants présentent 85 % d'homologie avec lesdites VEGF165R/NP-1 et NP-2, ou mieux 90 %, ou mieux encore 95 %, peut être utilisé.
PCT/US1998/026127 1997-12-09 1998-12-09 Neuropilines et leur utilisation a des fins de diagnostic et de pronostic du cancer Ceased WO1999030157A2 (fr)

Priority Applications (2)

Application Number Priority Date Filing Date Title
AU18108/99A AU1810899A (en) 1997-12-09 1998-12-09 Neuropilins and use thereof in methods for diagnosis and prognosis of cancer
US09/583,638 US6635421B1 (en) 1997-12-09 2000-05-30 Neuropilins and use thereof in methods for diagnosis and prognosis of cancer

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US6915597P 1997-12-09 1997-12-09
US60/069,155 1997-12-09
US6968797P 1997-12-12 1997-12-12
US60/069,687 1997-12-12

Related Child Applications (1)

Application Number Title Priority Date Filing Date
US09/583,638 Continuation US6635421B1 (en) 1997-12-09 2000-05-30 Neuropilins and use thereof in methods for diagnosis and prognosis of cancer

Publications (3)

Publication Number Publication Date
WO1999030157A2 WO1999030157A2 (fr) 1999-06-17
WO1999030157A3 WO1999030157A3 (fr) 1999-07-22
WO1999030157A9 true WO1999030157A9 (fr) 1999-10-21

Family

ID=26749747

Family Applications (2)

Application Number Title Priority Date Filing Date
PCT/US1998/026103 Ceased WO1999029861A1 (fr) 1997-12-09 1998-12-09 Peptides antagonistes du facteur de croissance de l'endothelium vasculaire
PCT/US1998/026127 Ceased WO1999030157A2 (fr) 1997-12-09 1998-12-09 Neuropilines et leur utilisation a des fins de diagnostic et de pronostic du cancer

Family Applications Before (1)

Application Number Title Priority Date Filing Date
PCT/US1998/026103 Ceased WO1999029861A1 (fr) 1997-12-09 1998-12-09 Peptides antagonistes du facteur de croissance de l'endothelium vasculaire

Country Status (5)

Country Link
EP (1) EP1037994A1 (fr)
JP (2) JP4312955B2 (fr)
AU (2) AU1810899A (fr)
CA (1) CA2313390A1 (fr)
WO (2) WO1999029861A1 (fr)

Families Citing this family (24)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7423125B2 (en) 1995-08-01 2008-09-09 Vegenics Limited Antibodies to VEGF-C
US6635421B1 (en) * 1997-12-09 2003-10-21 Children's Medical Center Corporation Neuropilins and use thereof in methods for diagnosis and prognosis of cancer
US7045133B2 (en) * 2000-01-18 2006-05-16 Ludwig Institute For Cancer Research VEGF-D/VEGF-C/VEGF peptidomimetic inhibitor
DE60131146T2 (de) 2000-02-25 2008-03-06 Ludwig Institute For Cancer Research Material und verfahren die hybridvaskularendothelwachstumfaktoren dns und proteine enthalten und screeningverfahren für modulatoren
US8263739B2 (en) 2000-06-02 2012-09-11 Bracco Suisse Sa Compounds for targeting endothelial cells, compositions containing the same and methods for their use
CA2410887C (fr) 2000-06-02 2012-07-24 Bracco Research Usa Composes pour le ciblage des cellules endotheliales, compositions les contenant et leurs procedes d'utilisation
AU2001285919B2 (en) * 2000-09-05 2007-08-23 Jiangsu Simcere Pharmaceutical R&D Co., Ltd Recombinant endothelial cell growth inhibitors derived from a mammalian plasminogen
GB0029015D0 (en) 2000-11-28 2001-01-10 Univ London Medical device
US7611711B2 (en) 2001-01-17 2009-11-03 Vegenics Limited VEGFR-3 inhibitor materials and methods
US7211240B2 (en) 2002-03-01 2007-05-01 Bracco International B.V. Multivalent constructs for therapeutic and diagnostic applications
WO2004065621A1 (fr) 2002-03-01 2004-08-05 Dyax Corp. Peptides de liaison kdr et vegf/kdr et leur utilisation a des fins diagnostiques et therapeutiques
US7794693B2 (en) 2002-03-01 2010-09-14 Bracco International B.V. Targeting vector-phospholipid conjugates
US7261876B2 (en) 2002-03-01 2007-08-28 Bracco International Bv Multivalent constructs for therapeutic and diagnostic applications
US8623822B2 (en) 2002-03-01 2014-01-07 Bracco Suisse Sa KDR and VEGF/KDR binding peptides and their use in diagnosis and therapy
GB0207644D0 (en) * 2002-04-02 2002-05-15 Ark Therapeutics Ltd Peptides and their use
DK2284180T3 (en) 2003-03-03 2015-12-21 Dyax Corp Uses of peptides that specifically bind to the HGF receptor (cMET)
RU2414924C2 (ru) * 2005-08-12 2011-03-27 Ридженерон Фармасьютикалз, Инк. Способы лечения заболеваний антагонистами vegf
AU2006279462A1 (en) 2005-08-15 2007-02-22 Vegenics Limited Modified VEGF and PDGF with improved angiogenic properties
BRPI0617488A2 (pt) * 2005-10-21 2011-07-26 Bayer Healthcare Llc mÉtodo para a monitoraÇço do estado de uma doenÇa associada a uma via de vegf-165 ativada por ultra-expressço ou por mutaÇço de proteÍna vegf-165 em um paciente, mÉtodo de seleÇço de terapia para um paciente humano com uma doenÇa e mÉtodo de dignàstico para detectar uma doenÇa associada a uma via de vegf-165 ativada por ultra-expressço ou por mutaÇço de proteÍna vegf-165 em um paciente
UA96139C2 (uk) 2005-11-08 2011-10-10 Дженентек, Інк. Антитіло до нейропіліну-1 (nrp1)
EP2524693B1 (fr) * 2010-01-14 2014-05-21 Sanwa Kagaku Kenkyusho Co., Ltd Produit pharmaceutique destiné au traitement prophylactique ou thérapeutique de troubles accompagnés d'une angiogenèse oculaire et/ou d'une perméabilité vasculaire oculaire supérieure à la normale
AU2011274528B2 (en) 2010-07-09 2015-04-23 Genentech, Inc. Anti-neuropilin antibodies and methods of use
JP2021521110A (ja) 2018-04-06 2021-08-26 エータイアー ファーマ， インコーポレイテッド 抗ｎｒｐ２抗体を含む組成物及び方法
AU2020358854A1 (en) 2019-10-03 2022-05-26 Atyr Pharma, Inc. Compositions and methods comprising anti-NRP2 antibodies

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1173991C (zh) * 1992-11-13 2004-11-03 马克斯普朗克科学促进协会 作为血管内皮生长因子受体的f1k-1
US6020473A (en) * 1995-08-25 2000-02-01 Genentech, Inc. Nucleic acids encoding variants of vascular endothelial cell growth factor

Also Published As

Publication number Publication date
EP1037994A1 (fr) 2000-09-27
WO1999030157A3 (fr) 1999-07-22
AU1906099A (en) 1999-06-28
CA2313390A1 (fr) 1999-06-17
JP4312955B2 (ja) 2009-08-12
JP2001526032A (ja) 2001-12-18
WO1999029861A1 (fr) 1999-06-17
AU1810899A (en) 1999-06-28
WO1999030157A2 (fr) 1999-06-17
JP2009148293A (ja) 2009-07-09

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