|On April 16, 2019, the Israeli Patent Office (IL PTO) held that an antibody targeting the same antigen as an antibody previously approved for patent term extension (PTE) was eligible for its own PTE provided that primary structural differences existed between the antibodies. In the event of post-translational differences (such as glycosylation), the IL PTO stated that it would be necessary for the patentee to show significant differences in activity.
The decision involved ocrelizumab (Ocrevus®), a humanized anti-CD20 monoclonal antibody marketed by Genentech, Inc. (Genentech) for the treatment of multiple sclerosis. Genentech filed a petition with the IL PTO to extend the term of the patent claiming the antibody. Under Israeli law, a PTE can only be granted when the regulatory approval is “the first regulatory approval permitting the use of the compound in Israel for pharmaceutical purposes”. In rejecting the application for PTE, the Examiner cited the earlier registration of the chimeric anti-CD20 monoclonal antibody rituximab (MabThera – marketed by Roche) used for the treatment of leukemia. Specifically, the Examiner argued: (i) ocrelizumab was the humanized form of rituximab; and (ii) both antibodies targeted the same CD20 antigen, bound to overlapping epitopes and were structurally similar. Thus, in the Examiner’s opinion, the antibodies were the same “compound”. Accordingly, the later approved ocreolizumab was not eligible for PTE.
On appeal, the Commissioner reversed. Specifically, the Commissioner adopted a three-stage test for evaluating the eligibility of a later approved antibody for PTE. This three-stage test involved evaluating the pathway, structure and function of the antibody in question. The first stage involved determining whether the product was approved as a New Active Substance (NAS). A product not approved as a NAS was not eligible for PTE; however, the opposite was also not true, namely, not every “new” product was eligible for PTE.
The second stage involved evaluating the structural differences between the products. The Commissioner held that antibodies which differed in their primary structure (e.g., such as in their amino acid sequence, particularly, in their CDR structure), were considered to be different active substances. With respect to ocrelizumab, one of the CDR loops which interacted with CD20 differed substantially from the rituximab counterpart in terms of its residue sequence and conformation. Thus, according to the Commissioner, ocrelizumab should be regarded as a new compound and thus eligible for PTE.
If, and only if, the structural differences between the antibodies are not significant (e.g., such as, if the differences involve post translational modifications such as glycosylation), is it be necessary to evaluate the third stage, namely, whether the differences have a substantial impact on activity (e.g., function) of the compound. Interestingly, the Commissioner did not elaborate on which functional differences would be sufficient to justify PTE eligibility and when or whether differences in pharmacokinetic parameters (such as bioavailability, half-life or in immunogenic effects) would suffice. It is expected that this aspect will be clarified in future decisions relating to PTE involving petitions currently in the pipeline.
Please continue to watch BRICS & Beyond for further updates on PTE in Israel.
This post was written by Lisa Mueller and Liad Whatstein of Liad Whatstein & Co.