Oncolytic non-human adenoviruses and uses thereof
AssigneeAcademisch Ziekenhuis Leiden (H.O.D.N. Lumc)
InventorsRob Cornelis HOEBEN, Selas BOTS, Vera KEMP
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Abstract
Novel nucleic acid sequences, vectors and adenoviral genomes are provided herein. Corresponding novel adenoviruses and genotypes and compositions are also provided. The novel nucleic acid sequences, vectors, genomes, adenoviruses, genotypes and compositions are useful in therapy. The novel nucleic acid sequences, vectors, genomes, adenoviruses, genotypes and compositions are particularly useful in treating or preventing cancer.
Claims32
An isolated nucleic acid sequence encoding a hexon polypeptide comprising an amino acid sequence having at least 95% identity to:
- amino acid residues 139 to 455 of SEQ ID NO:
- 23;
- amino acid residues 139 to 452 of SEQ ID NO:
- 57;
- or amino acid residues 139 to 453 of SEQ ID NO:
- 93.
An isolated nucleic acid sequence encoding a fiber polypeptide comprising an amino acid sequence having at least 95% identity to at least one of:
- amino acid residues 128 to 322 of SEQ ID NO:
- 22;
- amino acid residues 75 to 127 of SEQ ID NO:
- 22;
- amino acid residues 1 to 74 of SEQ ID NO:
- 22;
- amino acid residues 128 to 321 of SEQ ID NO:
- 56;
- amino acid residues 75 to 127 of SEQ ID NO:
- 56;
- amino acid residues 1 to 74 of SEQ ID NO:
- 56;
- amino acid residues 127 to 320 of SEQ ID NO:
- 92;
- amino acid residues 74 to 126 of SEQ ID NO:
- 92;
- or amino acid residues 1 to 73 of SEQ ID NO:
- 92.
An isolated nucleic acid sequence encoding a penton base polypeptide comprising an amino acid sequence having at least 95% identity to SEQ ID NO:
- 26, 60 or 96.
The isolated nucleic acid sequence of any preceding claim, wherein the sequence is selected from the group consisting of:
- (a) a nucleic acid sequence of SEQ ID NO:
- 1 and its complement;
- (b) a nucleic acid sequence of SEQ ID NO:
- 36 and its complement;
- and
- (c) a nucleic acid sequence of SEQ ID NO:
- 71 and its complement.
A vector comprising a nucleic acid sequence according to any preceding claim.
An isolated non-human primate adenovirus having a capsid comprising a capsid polypeptide of at least one of:
- (a) a hexon polypeptide comprising an amino acid sequence having at least 95% identity to:
- amino acid residues 139 to 455 of SEQ ID NO:
- 23;
- amino acid residues 139 to 452 of SEQ ID NO:
- 57;
- or amino acid residues 139 to 453 of SEQ ID NO:
- 93;
- (b) a hexon polypeptide comprising the amino acid sequence of amino acid residues 139 to 455 of SEQ ID NO:
- 23;
- amino acid residues 139 to 452 of SEQ ID NO:
- 57;
- or amino acid residues 139 to 453 of SEQ ID NO:
- 93;
- (c) a hexon polypeptide comprising the amino acid sequence of SEQ ID NO:
- 23, 57, or 93;
- (d) a fiber polypeptide comprising an amino acid sequence having at least 95% identity to at least one of:
- amino acid residues 128 to 322 of SEQ ID NO:
- 22;
- amino acid residues 75 to 127 of SEQ ID NO:
- 22;
- amino acid residues 1 to 74 of SEQ ID NO:
- 22;
- amino acid residues 128 to 321 of SEQ ID NO:
- 56;
- amino acid residues 75 to 127 of SEQ ID NO:
- 56;
- amino acid residues 1 to 74 of SEQ ID NO:
- 56;
- amino acid residues 127 to 320 of SEQ ID NO:
- 92;
- amino acid residues 74 to 126 of SEQ ID NO:
- 92;
- or amino acid residues 1 to 73 of SEQ ID NO:
- 92;
- (e) a fiber polypeptide comprising the amino acid sequence of at least one of:
- amino acid residues 128 to 322 of SEQ ID NO:
- 22;
- amino acid residues 75 to 127 of SEQ ID NO:
- 22;
- amino acid residues 1 to 74 of SEQ ID NO:
- 22;
- amino acid residues 128 to 321 of SEQ ID NO:
- 56;
- amino acid residues 75 to 127 of SEQ ID NO:
- 56;
- amino acid residues 1 to 74 of SEQ ID NO:
- 56;
- amino acid residues 127 to 320 of SEQ ID NO:
- 92;
- amino acid residues 74 to 126 of SEQ ID NO:
- 92;
- or amino acid residues 1 to 73 of SEQ ID NO:
- 92;
- (f) a fiber polypeptide comprising the amino acid sequence of SEQ ID NO:
- 22, 56 or 92;
- (g) a penton base polypeptide comprising an amino acid sequence having at least 95% identity to SEQ ID NO:
- 26, 60 or 96;
- or
- (h) a penton base polypeptide comprising the amino acid sequence of SEQ ID NO:
- 26, 60 or 96.
A pharmaceutical composition comprising an adenovirus, genome, isolated nucleic acid sequence, vector or protein of any preceding claim, and a pharmaceutically acceptable excipient, adjuvant, diluent and/or carrier.
Dependencies are inferred from the claim text.