ILPTO update: PTE Eligibility of Proteins

In a recent decision, the ILPTO Deputy Chief Examiner held that different glycosylation is insufficient to confer PTE eligibility if a protein with the same amino acid sequence was previously approved. The decision is inconsistent with previous ILPTO case law and we expect further clarification of the ILPTO position in the coming months.

The ILPTO rejected a PTE petition for the drug Nexviazyme (avalglucosidase alpha) on the grounds that its registration is not the first regulatory approval permitting the use of the API citing the previously registered drug Myozime (alglucosidase alfa). These APIs contain the same amino acid sequence of the enzyme but avalglucosidase alpha also has covalently attached glycan moieties. The Deputy Chief Examiner held that although the different glycosylation led to superior pharmacokinetic and pharmacodynamic properties, avalglucosidase alpha cannot be regarded as a new active substance because it has the same amino acid sequence and the same activity as the previously approved enzyme replacement therapy. The Examiner also held that the registration of Nexviazyme as a new drug product is insufficient by itself to confer PTE eligibility if the active substance had been previously approved.

The ILPTO decision with respect to avalglucosidase alpha appears overly strict and inconsistent with previous ILPTO case law in connection with PTE eligibility of novel recombinant proteins. For instance, in the Kovaltry (Factor VIII) decision, it was held that for a protein to be classified as a new active substance for PTE eligibility, it does not necessarily need to have an amino acid sequence which is different from that of a previously approved protein. It was also held in the Kovaltry decision that post translational modifications in glycosylation may suffice if they result in significant differences in activity, pharmacokinetics, immunogenicity or adverse events profile. The decision of the ILPTO Deputy Chief Examiner was appealed to the Deputy Commissioner and we expect that the ILPTO position with respect to PTE eligibility of proteins will be clarified in the near future.

This update article is provided for general information only and is not in lieu of legal advice. Please contact us directly for any required advice on specific matters.