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WO1996017931A1 - Facteur de croissance vasculaire humain proche de la proteine de fixation du facteur de croissance insulinoide - Google Patents

Facteur de croissance vasculaire humain proche de la proteine de fixation du facteur de croissance insulinoide Download PDF

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Publication number
WO1996017931A1
WO1996017931A1 PCT/US1994/014388 US9414388W WO9617931A1 WO 1996017931 A1 WO1996017931 A1 WO 1996017931A1 US 9414388 W US9414388 W US 9414388W WO 9617931 A1 WO9617931 A1 WO 9617931A1
Authority
WO
WIPO (PCT)
Prior art keywords
vigf
polypeptide
polynucleotide
dna
cells
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/US1994/014388
Other languages
English (en)
Inventor
Gregg A. Hastings
Craig A. Rosen
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.)
Human Genome Sciences Inc
Original Assignee
Human Genome Sciences Inc
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 to JP8517560A priority Critical patent/JPH10510518A/ja
Priority to AU14014/95A priority patent/AU710568B2/en
Priority to PCT/US1994/014388 priority patent/WO1996017931A1/fr
Priority to US08/849,107 priority patent/US5994302A/en
Priority to NZ278504A priority patent/NZ278504A/en
Priority to EP95905378A priority patent/EP0796325A4/fr
Application filed by Human Genome Sciences Inc filed Critical Human Genome Sciences Inc
Publication of WO1996017931A1 publication Critical patent/WO1996017931A1/fr
Anticipated expiration legal-status Critical
Priority to US09/037,460 priority patent/US20020034738A1/en
Priority to US10/951,866 priority patent/US20050069981A1/en
Priority to US11/848,047 priority patent/US20080057510A1/en
Priority to US12/544,413 priority patent/US20090311263A1/en
Ceased legal-status Critical Current

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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
    • C07K14/475—Growth factors; Growth regulators
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/06—Antihyperlipidemics
    • 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
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • 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
    • C12N2799/00—Uses of viruses
    • C12N2799/02—Uses of viruses as vector
    • C12N2799/021—Uses of viruses as vector for the expression of a heterologous nucleic acid
    • C12N2799/026—Uses of viruses as vector for the expression of a heterologous nucleic acid where the vector is derived from a baculovirus

Definitions

  • Figure 4 shows a gel which displays the results of a Northern Blot analysis performed on VIGF.
  • Figure 5 shows a gel which displays the results of a cell-type analysis of VIGF gene expression in the various tissues displayed.
  • Lane 1 is umbilical " vein endothelial cells
  • Lane 2 is aortic smooth muscle cells
  • Lane 3 is dermal foreskin fibroblast cells.
  • Figure 5A shows the results after a two hour exposure
  • Figure 5B shows the results after a thirty-six hour exposure.
  • polynucleotide encoding a polypeptide encompasses a polynucleotide which includes only coding sequence for the polypeptide as well as a polynucleotide which includes additional coding and/or non-coding sequence.
  • the present invention further relates to variants of the hereinabove described polynucleotides which encode for fragments, analogs and derivatives of the polypeptide having the deduced amino acid sequence of Figure 1 or the polypeptide encoded by the cDNA of the deposited clone.
  • the variant of the polynucleotide may be a naturally occurring allelic variant of the polynucleotide or a non-naturally occurring variant of the polynucleotide.
  • the polynucleotide may have a coding sequence which is a naturally occurring allelic variant of the coding sequence shown in Figure 1 or of the coding sequence of the deposited clone.
  • an allelic variant is an alternate form of a polynucleotide sequence which may have a substitution, deletion or addition of one or more nucleotides, which does not ⁇ ubstantially alter the function of the encoded polypeptide.
  • polynucleotides which hybridize to the hereinabove described polynucleotides in a preferred embodiment encode polypeptides which retain ⁇ ub ⁇ tantially the same biological function or activity as the mature polypeptide encoded by the cDNA of Figure 1 or the deposited cDNA.
  • the fragment, derivative or analog of the polypeptide of Figure 1 or that encoded by the depo ⁇ ited cDNA may be (i) one in which one or more of the amino acid residues are substituted with a conserved or non-conserved amino acid residue (preferably a conserved amino acid residue) and such substituted amino acid residue may or may not be one encoded by the genetic code, or (ii) one in which one or more of the amino acid residues includes a ⁇ ub ⁇ tituent group, or (iii) one in which the mature polypeptide is fused with another compound, such a ⁇ a compound to increa ⁇ e the half-life of the polypeptide (for example, polyethylene glycol), or (iv) one in which the additional amino acids are fu ⁇ ed to the mature polypeptide, such as a leader or secretory sequence or a sequence which is employed for purification of the mature polypeptide or a proprotein sequence.
  • Such fragments, derivative ⁇ and analog ⁇ are deemed to be within the ⁇
  • u ⁇ eful expre ⁇ ion vector ⁇ for bacterial u ⁇ e can compri ⁇ e a ⁇ electable marker and bacterial origin of replication derived from commercially available pla ⁇ mid ⁇ comprising genetic elements of the well known cloning vector pBR322 (ATCC 37017).
  • cloning vector pBR322 ATCC 37017
  • Such commercial vectors include, for example, pKK223-3 (Pharmacia Fine Chemicals, Uppsala, Sweden) and GEM1 (Promega Biotec, Madison, Wl, USA). These pBR322 "backbone" sections are combined with an appropriate promoter and the structural sequence to be expressed.
  • labeled VIGF can be photoaffinity linked with cell membrane or extract preparations that expres ⁇ the receptor molecule.
  • Cross-linked material is resolved by PAGE and exposed to X- ray film.
  • the labeled complex containing the VIGF-receptor can be excised, resolved into peptide fragments, and subjected to protein microsequencing.
  • the amino acid sequence obtained from microsequencing would be used to design a set of degenerate oligonucleotide probes to screen a cDNA library to identify the gene encoding the putative receptor.
  • VIGF receptor a mammalian cell or membrane preparation expres ⁇ ing the VIGF receptor would be incubated with labeled VIGF in the pre ⁇ ence of the compound. The ability of the compound to enhance or block thi ⁇ interaction could then be mea ⁇ ured. ALternatively, VIGF, labelled IGF and a potential compound could be incubated under condition ⁇ where VIGF would naturally bind to IGF. The extent of thi ⁇ interaction could be mea ⁇ ured to determine if the compound i ⁇ an effective antagoni ⁇ t or agonist.
  • VIGF antagonist ⁇ include small molecules which bind to the active site, the receptor binding site, IGF or other growth factor binding site of the polypeptide thereby blocking the normal biological activity of VIGF.
  • small molecules include but are not limited to small peptides or peptide-like molecules.
  • cells from a patient may be engineered with a polynucleotide (DNA or RNA) encoding a polypeptide ex vivo, with the engineered cells then being provided to a patient to be treated with the polypeptide.
  • a polynucleotide DNA or RNA
  • cell ⁇ may be engineered by procedures known in the art by use of a retroviral particle containing RNA encoding a polypeptide of the present invention.
  • cells may be engineered in vivo for expression of a polypeptide in vivo by, for example, procedures known in the art.
  • a producer cell for producing a retroviral particle containing RNA encoding the polypeptide of the present invention may be administered to a patient for engineering cells in vivo and expression of the polypeptide in vivo.
  • the expression vehicle for engineering cells may be other than a retrovirus, for example, an adenoviru ⁇ which may be used to engineer cells in vivo after combination with a suitable delivery vehicle.
  • ⁇ equence ⁇ can be mapped to chromosomes by preparing PCR primers (preferably 15-25 bp) from the cDNA. Computer analy ⁇ i ⁇ of the 3' untran ⁇ lated region i ⁇ u ⁇ ed to rapidly select primers that do not span more than one exon in the genomic DNA, thus complicating the amplification process. These primer ⁇ are then u ⁇ ed for PCR ⁇ creening of ⁇ omatic cell hybrid ⁇ containing individual human chromo ⁇ ome ⁇ . Only those hybrids containing the human gene corresponding to the primer will yield an amplified fragment. PCR mapping of somatic cell hybrids is a rapid procedure for assigning a particular DNA to a particular chromosome.
  • Ligase refers ⁇ to the proce ⁇ of forming pho ⁇ phodie ⁇ ter bond ⁇ between two double ⁇ tranded nucleic acid fragments (Maniati ⁇ , T., et al., Id., p. 146). Unless otherwise provided, ligation may be accomplished using known buffers and conditions with 10 units of T4 DNA ligase ("ligase”) per 0.5 ⁇ g of approximately equimolar amounts of the DNA fragments to be ligated.
  • ligase T4 DNA ligase
  • pQE-9 encodes antibiotic resistance (Amp r ), a bacterial origin of replication (ori), an IPTG-regulatable promoter operator (P/0), a ribosome binding site (RBS), a 6-His tag and restriction enzyme ⁇ ite ⁇ .
  • the VIGF PCR product and pQE-9 were then digested with Hind III and Xba I and ligated together with T4 DNA ligase.
  • the de ⁇ ired recombinant ⁇ would contain the VIGF coding ⁇ equence in ⁇ erted down ⁇ tream from the pQE-9 encoded histidine tag and the ribosome binding ⁇ ite.
  • the ligation mixture wa ⁇ then u ⁇ ed to tran ⁇ for E.
  • the plate is rocked back and forth to mix the newly added solution.
  • the plate is then incubated for 5 hours at 27°C.
  • the transfection solution is removed from the plate and 1 ml of Grace's insect medium supplemented with 10% fetal calf serum is added.
  • the plate is put back into an incubator and cultivation continued at 27°C for four days.

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • General Chemical & Material Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Animal Behavior & Ethology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Hematology (AREA)
  • Molecular Biology (AREA)
  • Obesity (AREA)
  • Toxicology (AREA)
  • Zoology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Biochemistry (AREA)
  • Biophysics (AREA)
  • Genetics & Genomics (AREA)
  • Diabetes (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)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)

Abstract

L'invention concerne un polypeptide du facteur de croissance humain vasculaire proche de la protéine de fixation du facteur de croissance insulinoïde (VIGF), et un ADN (ARN) codant pour ce polypeptide, ainsi qu'un mode opératoire de production de ce polypeptide par des techniques de recombinaison. Sont également décrits des procédés pour utiliser ce polypeptide en vue de favoriser la cicatrisation ou la régénération tissulaire, et de stimuler la fixation des implants et l'angiogénèse. L'invention concerne également des antagonistes de ces polypeptides et leur utilisation comme agent thérapeutique pour traiter l'athérosclérose, les tumeurs et la formation de cicatrices atrophiques. L'invention concerne d'autre part des dosages diagnostiques pour identifier des mutations dans des séquences d'acide nucléique de VIGF et des modifications de la concentration du polypeptide de VIGF.
PCT/US1994/014388 1994-12-09 1994-12-09 Facteur de croissance vasculaire humain proche de la proteine de fixation du facteur de croissance insulinoide Ceased WO1996017931A1 (fr)

Priority Applications (10)

Application Number Priority Date Filing Date Title
AU14014/95A AU710568B2 (en) 1994-12-09 1994-12-09 Human vascular IBP-like growth factor
PCT/US1994/014388 WO1996017931A1 (fr) 1994-12-09 1994-12-09 Facteur de croissance vasculaire humain proche de la proteine de fixation du facteur de croissance insulinoide
US08/849,107 US5994302A (en) 1994-12-09 1994-12-09 Human vascular IBP-like growth factor
NZ278504A NZ278504A (en) 1994-12-09 1994-12-09 Human vascular ibp-like growth factor polypeptide (vigf)
EP95905378A EP0796325A4 (fr) 1994-12-09 1994-12-09 Facteur de croissance vasculaire humain proche de la proteine de fixation du facteur de croissance insulinoide
JP8517560A JPH10510518A (ja) 1994-12-09 1994-12-09 ヒト血管ｉｂｐ様成長因子
US09/037,460 US20020034738A1 (en) 1994-12-09 1998-03-10 Human vascular ibp-like growth factor
US10/951,866 US20050069981A1 (en) 1994-12-09 2004-09-29 Human vascular IBP-like growth factor
US11/848,047 US20080057510A1 (en) 1994-12-09 2007-08-30 Human Vascular IBP-Like Growth Factor
US12/544,413 US20090311263A1 (en) 1994-12-09 2009-08-20 Human vascular ibp-like growth factor

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
PCT/US1994/014388 WO1996017931A1 (fr) 1994-12-09 1994-12-09 Facteur de croissance vasculaire humain proche de la proteine de fixation du facteur de croissance insulinoide

Related Child Applications (1)

Application Number Title Priority Date Filing Date
US08/464,339 Continuation-In-Part US5747280A (en) 1994-12-09 1995-06-05 Human vascular IBP-like growth factor

Publications (1)

Publication Number Publication Date
WO1996017931A1 true WO1996017931A1 (fr) 1996-06-13

Family

ID=22243393

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US1994/014388 Ceased WO1996017931A1 (fr) 1994-12-09 1994-12-09 Facteur de croissance vasculaire humain proche de la proteine de fixation du facteur de croissance insulinoide

Country Status (5)

Country Link
EP (1) EP0796325A4 (fr)
JP (1) JPH10510518A (fr)
AU (1) AU710568B2 (fr)
NZ (1) NZ278504A (fr)
WO (1) WO1996017931A1 (fr)

Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1999045028A1 (fr) * 1998-03-05 1999-09-10 Institut Pasteur De Lille Anticorps monoclonaux specifiques de la proteine esm-1, et utilisation de ces anticorps pour la detection de la proteine esm-1
FR2816214A1 (fr) * 2000-11-09 2002-05-10 Pasteur Institut Utilisation d'un compose antagoniste de la proteine esm-1 pour la fabrication d'un medicament pour la prevention et/ou le traitement d'un cancer
US6670328B1 (en) * 1997-06-24 2003-12-30 Institut Pasteur De Lille Proteins and peptides derived from protein ESM-1 and their uses in the treatment and diagnosis of diseases linked to leukocyte migration
EP1042674A4 (fr) * 1997-10-24 2005-03-23 Human Genome Sciences Inc 148 proteines humaines secretees
US7473564B2 (en) 2000-11-09 2009-01-06 Institut Pasteur De Lille Kit and method for detecting the ESM-1 protein
EP2042597A1 (fr) 2000-06-23 2009-04-01 Genentech, Inc. Compositions et procédés pour le traitement et le diagnostic des troubles impliquant une angiogénèse
EP2075253A1 (fr) 2000-06-23 2009-07-01 Genentech, Inc. Méthodes et composés pour la diagnose et le traitement de troubles associés à l'angiogenèse

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2642656B1 (fr) * 1989-02-09 1991-11-15 Salomon Sa Fixation de securite pour ski destinee a maintenir l'avant d'une chaussure montee sur le ski
JPH06503711A (ja) * 1990-08-28 1994-04-28 カイロン　コーポレイション 新規インシュリン様成長因子結合タンパク質（ｉｇｆｂｐ―４）
EP0546110B1 (fr) * 1990-08-28 2001-11-14 Chiron Corporation Nouvelle proteine de liaison de facteur de croissance analogue a l'insuline igfbp-5
DE69233155T2 (de) * 1991-01-08 2004-06-03 Chiron Corp. (N.D.Ges.D. Staates Delaware), Emeryville Insulinartigen wachstumsfaktor bindendes protein

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
ATHEROSCLEROSIS, Volume 93, issued 1992, M. KHORSANDI et al., "Effects of Hypophysectomy on Vascular Insulin-like Growth Factor-I Gene Expression After Balloon Denudation in Rats", pages 115-122. *
JOURNAL OF CELL BIOLOGY, Volume 114, Number 6, issued September 1991, D.M. BRADHAM et al., "Connective Tissue Growth Factor: a Cysteine-rich Mitogen Secreted by Human Vascular Endothelial Cells is Related to the SRC-induced Immediate Early Gene Product CEF-10", pages 1285-1294. *
See also references of EP0796325A4 *

Cited By (14)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6670328B1 (en) * 1997-06-24 2003-12-30 Institut Pasteur De Lille Proteins and peptides derived from protein ESM-1 and their uses in the treatment and diagnosis of diseases linked to leukocyte migration
EP1042674A4 (fr) * 1997-10-24 2005-03-23 Human Genome Sciences Inc 148 proteines humaines secretees
FR2775691A1 (fr) * 1998-03-05 1999-09-10 Pasteur Institut Anticorps monoclonaux specifiques de la proteine esm-1, et utilisation de ces anticorps pour la detection de la proteine esm-1
WO1999045028A1 (fr) * 1998-03-05 1999-09-10 Institut Pasteur De Lille Anticorps monoclonaux specifiques de la proteine esm-1, et utilisation de ces anticorps pour la detection de la proteine esm-1
EP2077276A1 (fr) 2000-06-23 2009-07-08 Genentech, Inc. Compositions et procédés pour le traitement et le diagnostic des troubles impliquant une angiogenèse
EP2792747A1 (fr) 2000-06-23 2014-10-22 Genentech, Inc. Compositions et procédés pour le traitement et le diagnostic des troubles impliquant une angiogenèse
EP2275549A1 (fr) 2000-06-23 2011-01-19 Genentech, Inc. Compositions et procédés pour le traitement et le diagnostic des troubles impliquant une angiogénèse
EP2168980A1 (fr) 2000-06-23 2010-03-31 Genentech, Inc. Compositions et procédés pour le traitement et le diagnostic des troubles impliquant une angiogenèse
EP2042597A1 (fr) 2000-06-23 2009-04-01 Genentech, Inc. Compositions et procédés pour le traitement et le diagnostic des troubles impliquant une angiogénèse
EP2075253A1 (fr) 2000-06-23 2009-07-01 Genentech, Inc. Méthodes et composés pour la diagnose et le traitement de troubles associés à l'angiogenèse
WO2002038178A1 (fr) * 2000-11-09 2002-05-16 Institut Pasteur De Lille Utilisation d'un compose antagoniste de la proteine esm-1 pour la fabrication d'un medicament pour le traitement d'un cancer
US7473564B2 (en) 2000-11-09 2009-01-06 Institut Pasteur De Lille Kit and method for detecting the ESM-1 protein
US7306797B2 (en) 2000-11-09 2007-12-11 Institut Pasteur De Lille Use of a compound antagonist of ESM-1 protein for producing a medicine for treating cancer
FR2816214A1 (fr) * 2000-11-09 2002-05-10 Pasteur Institut Utilisation d'un compose antagoniste de la proteine esm-1 pour la fabrication d'un medicament pour la prevention et/ou le traitement d'un cancer

Also Published As

Publication number Publication date
EP0796325A4 (fr) 1999-11-03
AU1401495A (en) 1996-06-26
EP0796325A1 (fr) 1997-09-24
NZ278504A (en) 1999-10-28
AU710568B2 (en) 1999-09-23
JPH10510518A (ja) 1998-10-13

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