Use of VEGF-C to prevent restenosis
AssigneesLicentia Ltd., Seppo Yla-Herttuala, Ludwig Institute of Cancer Research
InventorsKari Alitalo, Seppo Ylä-Herttuala, Mikko O. Hiltunen, Markku M. Jeltsch, Marc G. Achen
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Abstract
The present invention provides materials and methods for preventing stenosis or restenosis of a blood vessel using Vascular Endothelial Growth Factor C (VEGF-C) and/or Vascular Endothelial Growth Factor D (VEGF-D) genes or proteins.
Claims27
A method of treating a mammalian subject to inhibit restenosis of a blood vessel, comprising the step of:
- administering to a mammalian subject in need of treatment to inhibit restenosis of a blood vessel a composition comprising a replication-deficient adenovirus comprising a polynucleotide,
- wherein said composition is administered locally at the site in need of treatment to inhibit restenosis,
- wherein said polynucleotide comprises a nucleotide sequence that encodes a vascular endothelial growth factor C (VEGF-C) polypeptide operatively linked to a promoter to promote expression of the VEGF-C polypeptide in cells of the blood vessel,
- wherein the VEGF-C polypeptide comprises:
- the amino acid sequence of SEQ ID NO:
- 2;
- and
- wherein expression of said VEGF-C polypeptide in said blood vessel cells inhibits restenosis of said blood vessel.
A treatment to inhibit restenosis of a blood vessel in a human, comprising delivering a replication-deficient adenovirus vector to the vessel, said vector comprising a polynucleotide encoding a VEGF-C polypeptide, and further comprising a promoter sequence to promote expression of the VEGF-C polypeptide in cells of the blood vessel, wherein expression of said VEGF-C polypeptide in said blood vessel cells inhibits restenosis of the blood vessel, and
- wherein the VEGF-C polypeptide comprises
- the amino acid sequence of SEQ ID NO:
- 2.
An improvement in a medical device designed to contact a surface of a blood vessel in the course of surgery to treat stenosis of the blood vessel, said improvement comprising integrating into the device a composition effective to prevent restenosis, said composition comprising a replication-deficient adenovirus comprising a VEGF-C polynucleotide operatively linked to a promoter that promotes expression of a VEGF-C polypeptide encoded by the polynucleotide in cells of blood vessels,
- wherein the VEGF-C polypeptide comprises
- the amino acid sequence of SEQ ID NO:
- 2.
A medical device comprising an endovascular stent having an outer surface for contacting a surface of a blood vessel, and a composition on said surface, said composition comprising a replication-deficient adenovirus comprising a VEGF-C polynucleotide operatively linked to a promoter that promotes expression of VEGF-C polypeptide encoded by the polynucleotide in cells of blood vessels,
- wherein the VEGF-C polypeptide comprises
- the amino acid sequence of SEQ ID NO:
- 2.
A medical device comprising a catheter having an outer surface for contacting a surface of a blood vessel, and a composition on said surface, said composition comprising a replication-deficient adenovirus comprising a VEGF-C polynucleotide operatively linked to a promoter that promotes expression of VEGF-C polypeptide encoded by the polynucleotide in cells of blood vessels,
- wherein the VEGF-C polypeptide comprises
- the amino acid sequence of SEQ ID NO:
- 2.
A medical device comprising a balloon catheter having a void for holding a therapeutic agent for delivery to the interior of a blood vessel, and a composition contained in the void, the composition comprising a replication-deficient adenovirus comprising a VEGF-C polynucleotide operatively linked to a promoter that promotes expression of VEGF-C polypeptide encoded by the polynucleotide in cells of blood vessels,
- wherein the VEGF-C polypeptide comprises
- the amino acid sequence of SEQ ID NO:
- 2.
A method of treating a mammalian subject to inhibit restenosis of a blood vessel, comprising:
- identifying a mammalian subject that has been or will be treated for a stenosed blood vessel;
- and
- administering to the mammalian subject at the site of the stenosed blood vessel a composition comprising a replication-deficient adenovirus comprising a polynucleotide, said polynucleotide comprising a nucleotide sequence that encodes a vascular endothelial growth factor C (VEGF-C) polypeptide,
- wherein the VEGF-C polypeptide comprises
- the amino acid sequence of SEQ ID NO:
- 2;
- wherein the polynucleotide includes a promoter sequence operably linked to the encoding sequence to promote expression of the polypeptide in cells of the blood vessel, and
- wherein expression of the VEGF-C polypeptide inhibits restenosis of said blood vessel.
An extravascular collar designed to contact a surface of a blood vessel in the course of surgery to treat stenosis of the blood veseel, the collar comprising an outer wall shaped to surround the outer surface of a blood vessel, wherein the wall encloses a space containing a composition comprising a replication-deficient adenovirus comprising a polynucleotide that comprises a nucleotide sequence encoding a VEGF-C polypeptide;
- wherein the VEGF-C polypeptide comprises
- the amino acid sequence of SEQ ID NO:
- 2;
- wherein the polynucleotide further comprises a promoter to promote expression of the polypeptide in mammalian cells.
Dependencies are inferred from the claim text.