Patent ID: 11969462
Assignee: TRANSGENE
Field: Pharmaceuticals (Chemistry)
Classification: CPC A  C | IPC A  C

Claim 0:
1. A process for preparing a recombinant poxvirus comprising a heterologous nucleic acid sequence encoding a neopeptide fusion comprising 2 to 15 neopeptides, said process comprising:
(a) identifying a plurality of selected neopeptides, wherein the identification step comprises the following sub-steps i) to v):
i) extracting nucleic acids from a tumor sample and a non-tumor sample;
ii) sequencing corresponding regions from the extracted nucleic acids from the tumor sample and the non-tumor sample;
iii) comparing the nucleic acid sequences obtained from the tumor and non-tumor samples to identify a plurality of tumor specific mutations;
iv) determining the tumor specific mutations that are expressed at the mRNA expression and/or protein translation level in the tumor sample to identify one or more neoantigens, wherein the one or more neoantigens comprise a plurality of potential neopeptides; and
v) identifying and selecting from the plurality of potential neopeptides those that are not present in the proteome of the non-tumor sample to obtain the plurality of selected neopeptides;

(b) generating amino acid sequences for a plurality of potential neopeptide fusions, wherein each potential neopeptide fusion comprises the amino acid sequences of 2 to 15 of the selected neopeptides, optionally comprising intervening linker sequences of 2 to 15 amino acids between one or more of the selected neopeptide sequences, wherein at least 60% of the selected neopeptides in each potential neopeptide fusion comprise a missense or a frameshift mutation;
(c) determining the degree of hydrophobicity of each of said potential neopeptide fusions and selecting a neopeptide fusion that has a negative hydrophobicity score and/or a hydropathy score equal or below 0.1;
(d) generating a nucleic acid fusion sequence for said selected neopeptide fusion; and
(e) generating a recombinant poxvirus by inserting a nucleic acid molecule comprising said nucleic acid fusion sequence into the genome of a parental recombinant poxvirusi wherein the poxvirus is a vaccinia virus.