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Home Gene Therapy Vascular-endothelial-growth-factor-D-VEGF-D-polypeptides

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 Vascular endothelial growth factor-D (VEGF-D) polypeptides

Details
Inventors: Achen, Marc G.; Wilks, Andrew F.; Stacker, Steven A.; Alitalo, Kari;
Assignee: Ludwig Institute for Cancer Research (New York, NY); Helsinki University Licensing Ltd. (Helsinki, FI)
Primary Examiner: Saoud; Christine
Assistant Examiner:
Attorney, Agent or Firm: Evenson, McKeown, Edwards & Lenahan, P.L.L.C.

VEGF-D, a new member of the PDGF family of growth factors, which among other things stimulates endothelial cell proliferation and angiogenesis and increases vascular permeability, as well as nucleotide sequences encoding it, methods for producing it, antibodies and other antagonists to it, transfected or transformed host cells for expressing it, pharmaceutical compositions containing it, and uses thereof in medical and diagnostic applications.

DETAILED DESCRIPTION OF THE INVENTION The invention will now be described in detail by reference to the figures, and to the following non-limiting examples.
EXAMPLE 1 It has been speculated that no further members of the VEGF family will be found, because there are no known orphan receptors in.
the VEGFR family.
Furthermore, we are not aware of any suggestion in the prior art that other such family members would exist.
A computer search of nucleic acid databases was carried out incidentally to another project, using as search topics the amino acid sequences of VEGF, VEGF-B, VEGF-C and PlGF.
Several cDNA sequences were identified by this search.
One of these sequences, GenBank Accession No.
H24828, encoded a polypeptide which was similar in structure to the cysteine-riched C-terminal region of VEGF-C.
This sequence was obtained from the database of expressed sequence tags (dbEST), and for the purposes of this specification is designated XPT.
The XPT cDNA had been isolated from a human cDNA library designated "Soares Breast 3NbHBst", which was constructed using mRNA from an adult human female breast tissue.
As far as can be ascertained this was normal breast tissue.
Sequencing of the XPT DNA was performed pursuant to the Integrated Molecular Analysis of Genome Expression Consortium (IMAGE Consortium), which solicits cDNA libraries from laboratories around the world, arrays the cDNA clones, and provides them to other organizations for sequencing.
The XPT sequence shown in the database was 419 nucleotides long, and encoded an amino acid sequence similar to the C-terminal 100 amino acids of VEGF-C, i.
e.
approximately residues 250 to 350, using the numbering system of Joukov et al (1996).
Similarly cysteine-rich regions are found in other proteins, which are entirely unrelated in function to the VEGF family, for example the secreted silk-like protein sp185 synthesized in the salivary glands of the midge Chironomus tentans.
This protein is encoded by the gene BR3, located in a Balbiani ring, a tissue specific chromosome "puff" found on polytene chromosomes in the midge salivary gland (Dignam and Case: Gene, 1990 88 133-140; Paulsson et al, J



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