America-Israel Patent Law

A Good Explanation of the Problem with "Progressive" Views of Big Pharma

James Meigs has a piece in the newest edition of Commentary entitled "Thank God For Big Pharma".  It doesn't say anything that's not already familiar to people involved in the pharmaceutical development process, but it's still a good read.  My only criticism: he doesn't mention Bayh-Dole, but he does discuss what would happen if the private sector were taken out of the drug development process, which is what some politicians seem to be angling for (by depriving drug companies of profits).  As I've said more than once before, I'd rather someone make huge profits and there be new drugs (or in the past year, new coronavirus vaccines) than no one make huge profits and there be no new drugs; and I'm glad there's a generic drug industry to make sure that, in nearly all cases, those drugs eventually become generic, at which point their prices drop precipitously. Together those two things drive new drug development.

Webinar on Israel's Compulsory Licensing of Kaletra and the Role of IP in the Corona Virus Pandemic

The Israel Embassy in Geneva has organized a webinar that will take place on May 7 at 16:00 Israel time (09:00 Eastern time in the US).  The main speaker will be Howard Poliner from the Ministry of Justice, who was one of the lawyers who helped draft the Government Order giving Israel the right to use several Abbvie patents, as discussed previously here, here and here.  Howard will be speaking not only about the GO but about the role of IP in the larger picture of fighting corona virus - including the fact that, without patents, there will fewer tools available with which to fight.  Rumor has it that others from the pharma industry, including a speaker from Abbvie, as well as spokespersons for other countries, will also be speaking. 

The webinar is free, but advanced registration is required. The webinar will also be streamed on Facebook.

Download WebTalk-Israel-Invitation-IP

 

 

Abbvie To Suspend Enforcement of Kaletra Patents (Maybe); Probably Unrelated to Israel

After last week's fanfare (in Israel, anyway) about the Israeli government exercising rights under section 104 of the patent statute to allow importation of a generic of Abbvie's Kaletra tablets, this week reports are surfacing that Abbvie is suspending enforcement of its Kaletra patents worldwide, or possibly waiving its rights altogether, if the reporting in The Financial Times is accurate.  The FT piece seems to imply that Abbvie took this course of action as a result of Israel's action, but that conclusion is questionable.  As one person working for the state of Israel noted, it's clear that Abbvie couldn't meet demand at the present time, so why not allow others to supply the drug?  And given the unimpressive results from tests in China in January, it's likely that Abbvie suspects, or possibly already knows, that the drug will be ineffective against COVID-19.  In which case it's a publicity win for Abbvie. 

It's worth noting that there's nothing on Abbvie's site about this.  While the FT report begins by stating, dramatically, "AbbVie is giving up its patents on a combination drug that is being studied as a coronavirus treatment", the FT story later says "The company gave notice of the change last week, according to a document seen by the Financial Times..."  Inasmuch as that document isn't presented on FT's site, Abbvie evidently only showed it under an agreement of confidentiality. 

Since Kaletra is used to keep HIV/AIDS in check, but not to eradicate the disease, and therefore must be taken regularly by patients, it's difficult to believe that Abbvie would willingly forfeit profits from the drug in those countries where patent protection is still in force.  Perhaps Abbvie has simply indicated it won't enforce its patent against importers who import for purposes of COVID-19 testing.  Time will tell.

A Few More Thoughts On Israel’s Exercising Its Right to Exploit Abbvie’s Patents

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.

Israel Makes First Use of Statutory Provision Allowing Patent Infringement By State

The Israel Patent Statute was enacted in 1967.  Despite being amended several times since then, most recently in 2012, it has always contained two provisions to enable third parties to exploit a patent against the patentee’s wishes. 

One way, set forth in sections 116-128 of the statute, is via compulsory license, which is when a competitor of the patentee tells the Patents Commissioner that the patentee is being unreasonable about licensing terms and that this is hurting the public, and the Commissioner grants the competitor a license to practice the patent.  Until early 1995, this modus operandi was commonly used by local drug manufacturers. Then, in the space of about a month, the Tel-Aviv District Court ruled that the ILPTO shouldn’t have issued compulsory licenses for acyclovir (Zovirax) and fluoxetine (Prozac) and found the licensees to have infringed the patents.  That pretty much ended compulsory licenses in Israel, but for good measure, a few years later, Israel amended the statute to comply with GATT-TRIPs, tightening up the requirements for a compulsory license.  I don’t think any have been granted in the past 25 years.

The second way is when the state itself wishes to exploit the patented invention for the sake of national security or for the maintenance of the supply of essential goods and services.  That’s codified in sections 104-106, and hitherto had never been used.  That changed this week, when the Health Minister signed an order allowing the importation of a drug that combines two anti-retroviral active ingredients, lopinavir and ritonavir.  The drug is sold by Abbvie under the name Kaletra, and is presently approved for use in combination with other retroviral drugs to keep AIDS under control in infected patients. 

There are presently nine patents listed in the FDA Orange Book for Kaletra, although one of them lists the expiration date as January 19, 2020, and so should probably be removed.  These patents claim solid pharmaceutical dosage forms as well as methods of treating AIDS.  The order lists three Israel patents still in force that ostensibly cover the product, namely IL 173939, 185930 and 207260. Inasmuch as the prescribing information says that the drug was first approved by the FDA in 2000, whatever patents there are in Israel that cover the current product are unlikely to have too much more life to them.  (IL 173939 and its child 207260 will expire at the latest in August 2024; 183930 will expire at the latest in February 2026, but for reasons I'll discuss in another post, it's not clear this patent needed to be included in the order.)

There’s some hope that Kaletra will also be useful in treating COVID-19 (novel coronavirus), and a Korean hospital announced in February that it had successfully treated a patient with a combination of lopinavir and ritonavir, so there’s suddenly a demand for the drug, and not only in Israel, where there as of this writing still fewer than 500 reported coronavirus infections (and no deaths).  But Abbvie can’t meet that demand.  So the authorities are exercising their right under sections 104-106 of the statute to import generic Kaletra from countries in which there is no patent protection, most notably India.

The MOH (or rather, the team of lawyers in the Justice Ministry, MOH and ILPTO behind the Order) was careful to couch the order as applying only to importation of a particular version of the drug (containing 200 mg liponavir and 50 mg ritonavir), from a particular manufacturer, and for treating coronavirus only ; the state is not allowing itself to import for treating AIDS.  And per the statute, Abbvie will be entitled to compensation for the importation, though just how much will be determined at a later date, either by agreement between the state and Abbvie, or in the absence of such an agreement by the Compensation and Royalties Committee that is established by the ILPTO on an ad hoc basis.