As I mentioned yesterday, the Minister of Health signed an order this week allowing the state to import generic Kaletra (a combination of lopinavir and ritonavir) to be used, potentially, against COVID-19. I’d like to share two observations about this.
The first is that, despite the increasingly strict isolation measures the state has been putting in place over the past several weeks – people are now supposed to leave their homes only in very limited circumstances – these strictures are being emplaced in a manner that English speakers would says comports with the Rule of Law: the state is following its own legal procedures, to the point that implementation of the latest set of restrictions was delayed by several days until they could be properly published in the Israeli equivalent of the Federal Register.
This approach can be seen in how the Health Minister’s order allowing importation of generic Kaletra came about, and what the order says. The state didn’t say, “We’re the state and we can infringe willy-nilly”, let alone start importing generic product without informing the patentee or its licensed importer. The state followed the patent statute. The order itself invoking the state’s statutory rights was prepared by a team of lawyers from several state offices who worked behind the scenes, and those lawyers are not anonymous, but are well-known to people who work in IP in Israel. And, I as noted yesterday, the order is fairly limited in its scope: it’s for a specific solid-state formulation, and is only to be used in corona virus treatment, not treatment of HIV/AIDS. Moreover, the order was issued because the patentee, Abbvie, can’t keep up with demand. Presumably, if Abbvie could keep up with demand, the state would not exercise its rights to import.
Additionally, the patentee will be entitled to compensation for the infringement. It remains to be seen where that will be set, but no one expects Abbvie to walk away from this with nothing.
It instills a measure of confidence that even in tough times, the state makes an effort to follow its own laws. That’s not a given in many parts of the world.
The second observation is that of the three patents listed in the order, the inclusion of two of them is questionable. IL 173939 and IL 207260 are a parent and divisional, and they claim a solid pharmaceutical form per se and a method of making a solid pharmaceutical form. The independent claim of IL 173939 reads,
1. A solid pharmaceutical dosage form which comprises a solid dispersion of at least one HIV protease inhibitor selected from the group consisting of lopinavir, ritonavir, and a mixture thereof, at least one pharmaceutically acceptable water-soluble polymer having Tgof at least 50ᵒC, wherein said water-soluble polymer constitutes from 50 to 85% by weight of the total weight of the dosage form, and at least one pharmaceutically acceptable non-ionic surfactant having HLB value from 4 to 10.
That claim, and several other claims of the ‘939 patent, are presumably infringed by the importation of generic Kaletra.
The independent claim of 207260 reads,
1. A method of preparing a pharmaceutical solid dosage form, comprising:preparing a homogeneous melt of at least one HIV protease inhibitor selected from the group consisting of lopinavir, ritonavir and a mixture thereof,at least one pharmaceutically acceptable water-soluble polymer having Tg of at least 50ᵒC,andat least one pharmaceutically acceptable non-ionic surfactant having HLB value from 4 to 10, wherein the melt is prepared by melt-extrusion; allowing the melt to solidify to obtain a solid dispersion product; and forming tablets, wherein the tablets further comprise one or more additives selected from the group consisting of flow regulators, disintegrants, bulking agents and lubricants.
If the manufacturer uses an infringing process to make its product, then importation of the drug constitutes infringement, and Abbvie will argue it is entitled to compensation for such infringement. But it’s also possible that this claim is not infringed by the process by which the generic Kaletra is manufactured, in which case the state will argue that Abbvie isn’t entitled to such compensation. The bottom line is that to obtain royalties on the basis of the ‘260 patent for the importation of the generic drug, Abbvie will need to show that the imported material is prepared by the claimed process.
The third patent listed in the order, IL 185930, has two independent claims:
1. Use of a solid dispersion comprising lopinavir and ritonavir; at least one pharmaceutically acceptable water-soluble polymer having Tg of at least 50ᵒC, wherein said water-soluble polymer constitutes from 50 to 85% by weight of the total weight of the dosage form; and at least one pharmaceutically acceptable non-ionic surfactant having HLB value from 4 to 10, in the preparation of a medicament for treating HIV/AIDS in a patient in fasted state.
3. Use of a solid dispersion comprising lopinavir and ritonavir; at least one pharmaceutically acceptable water-soluble polymer having Tg of at least 50ᵒC, wherein said water-soluble polymer constitutes from 50 to 85% by weight of the total weight of the dosage form; and at least one pharmaceutically acceptable non-ionic surfactant having HLB value from 4 to 10, in the preparation of a medicament that is taken without food for treating HIV/AIDS in a patient.
Both of these claims are in “Swiss” format, a format that is used in many countries that prohibit the patenting of methods of treatment of people (often on moral grounds), as a way to get around such prohibitions. The intended use recited at the end of these two claims would presumably be understood by a court in Israel as limiting these claims to methods of preparation of formulations that are intended for use in treating HIV/AIDS. Since the Health Minister’s order is limited to importation for the treatment of corona virus, that importation presumably doesn’t infringe.
Then again, maybe it does: the generic drug that will be imported is made in India, and as all approvals of the drug worldwide at this time are for the treatment of HIV/AIDS, Abbvie will likely argue that the manufacture of the drug product meets all the limitations of these two claims – the drug is being made for treating HIV/AIDS – and that the fact that Israel is importing the drug for an off-label use doesn’t change the fact that the drug was manufactured for the treatment of HIV/AIDS. Abbvie will thus seek additional compensation on this basis.
What I find particularly interesting about the inclusion of the ‘260 patent in the Minister’s order is that a few years ago, the Israel PTO sua sponte stopped accepting Swiss style claims, on the grounds that such claims do not recite a product or process. That reversal of position contradicted decades of precedent in which such claims had been accepted by the ILPTO, and in which such claims had been litigated and not once found to be invalid on the grounds that Swiss claims per se are unacceptable.
It is tempting to think that the fact that one of the lawyers involved in preparing this week’s importation order works in the ILPTO signals a change of heart on the part of the ILPTO, but that’s probably reading too much into it: my understanding is that the lawyers who drafted the order didn’t actually look at the patents, and merely listed those that they were told by the patentee or the patentee’s licensed importer might be infringed by unauthorized parallel importation. If the state and Abbvie are unable to come to terms about the appropriate compensation, and the matter goes to the Compensation and Royalties Committee for adjudication, the question of the permissibility of Swiss claims per se may finally be addressed head-on.