Update on IL PTE practice on biological drugs and PTE filing deadlines

Liad Whatstein of Liad Whatstein & Co has kindly provided the following updates on patent term extensions on biological drugs and filing deadlines in Israel.

Israeli PTO clarifies rules on Patent Term Extensions for Biological Drugs 

In a recent precedential decision, the IL PTO held for the first time that biological products which contain an earlier approved protein may be eligible for PTE if it can be shown that structural differences between the proteins such as differences in glycosylation have an impact on the activity or pharmacokinetic profile of the protein. If sufficient evidentiary basis is provided with the PTE petition, this important decision will make it possible to obtain PTE orders for biological drugs which contain as the active ingredient proteins that carry the same INN (international nonproprietary name) as in previously approved drugs. 

The decision involved a petition filed by Bayer to extend the term of a patent claiming the production method of the drug KOVALTRY, a recombinant human coagulation Factor VIII. Under Israeli law, patent term extension can only be granted when the regulatory approval “is the first regulatory approval permitting the use of the compound in Israel for pharmaceutical purposes”. The examiner cited against the PTE petition several earlier registrations of Factor VIII products and, in particular, an earlier Bayer Factor VIII product, KOGENATE. The examiner’s position was that earlier registrations of products containing Factor VIII preclude the eligibility for PTE of later products containing Factor VIII, irrespective of differences in the properties or methods of manufacture of the protein. 

On appeal, the Commissioner upheld the rejection of the PTE petition for KOVALTRY but adopted a significantly more flexible approach. The Commissioner recognized that an approach whereby any earlier registration of a protein of the same name precludes eligibility for PTE for later products does not take into account potential differences between biological products. The Commissioner therefore set a two-step test to determine eligibility for PTE for biological products. First, a biological drug that has been approved as a biosimilar will not be eligible to PTE. Second, if the drug was approved as a new drug, it will be necessary to evaluate whether the protein is structurally different from similar proteins which have been previously approved and whether such structural differences have an impact on activity. Structural differences can among others be in the amino acid sequences, the three-dimensional conformation or glycosylation. Functional differences can among others relate to pharmacokinetic parameters of the drug such as bioavailability or half-life or to different immunogenic effects. 

In the present matter, the drug was approved as a new biological drug. The patentee demonstrated that it manufactured the drug using a recombinant process which is different from the recombinant process used to manufacture the earlier Factor VIII drug. The patentee also showed that the later Factor VIII product differs from the previous product in the level of highly branched sialylated glycans and the level of α-gal-linked glycans. The Commissioner recognized that even minor structural differences can result in functional differences which will support a PTE. However, the patentee failed to produce evidence to establish that the structural differences are translated into a different pharmacokinetic profile or to any benefit to patients. Therefore, even under the Commissioner’s flexible approach, the PTE petition was denied but the principles determined in the decision are very significant for future reference by patentees (Decision dated April 16, 2018 in Petition to extend IL 124123 in the name of Bayer Healthcare LLC). 

New rules for determining the 90-day deadline for filing a PTE petition under Israeli law 

Under Israeli law, a petition for Patent Term Extension must be submitted within 90 days from “the date of registration of the pharmaceutical preparation” in the Israeli Drug Register. The deadline is non-extendable. Late filing will result in the loss of eligibility for PTE. 

Under the PTO traditional practice, the PTO has counted the deadline as of the date of registration which appears on the Marketing Approval. In a new decision, the Commissioner of Patents held that the 90-day deadline is to be counted from the date of delivery of the marketing approval by the Ministry of Health to the owner of the registration and not from the date of registration. The date of delivery may be a few days after the date of registration. Furthermore, if the registrant proves that the marketing approval did not reach it on the delivery date, the 90-day deadline will start upon the date of actual notice that a marketing approval was issued (Decision dated April 16, 2018 in Petition to extend IL 124123 in the name of Bayer Healthcare LLC). 

This new decision should also be seen as another favorable development following the 2016 PTO change in practice with regard to the determination of the date of the earliest Marketing Approval in the Recognized Countries for the calculation of the 14 years cap for the PTE duration. The PTO aligned its position with the CJEU ruling in case C 471/14 Seattle Genetics which held that the calculation of the duration of supplementary protection should be based on the EMA MA notification date rather than the EMA MA grant date. In late 2017, after discussions at the Knesset Law Committee in which Liad Whatstein & Co. took part and despite protest by the Israeli generic industry, new Regulation 2(c)(3) of the PTE Regulations endorsed the 2016 PTO change in practice. 

Thanks Liad!

Update on IL PTE practice: Notification date of MA to be used in calculating PTE duration

Liad Whatstein of Liad Whatstein & Co. brings news of a recent decision of the Israeli Patent Office regarding the calculation of the duration of Israeli patent term extensions (PTEs).  Liad represented Novartis in the IL PTE petition for secukinumab (Cosentyx®).  He writes:

The Israel PTO recently accepted that for the purpose of calculating the duration of IL PTEs the EMA MA notification date shall be taken into account. This development changes the practice of the IL PTO and comes only a few months after the IL Patents Commissioner held that the EMA MA grant date should be used.

The Israeli PTE system is unique and is based on a series of linkages to the expiry dates and extension periods of the US PTE and SPCs granted in any of the EU-5 countries (United Kingdom, Italy, France, Spain and Germany). In addition, the Israeli PTE must end no later than 14 years from the earliest date in which a regulatory approval was obtained in either the Unites States or the EU-5 countries.

In the matter of IL PTE petition for Apixaban (Eliquis®) published on September 16th, 2015, the IL Patents Commissioner held that for the purpose of calculating the duration of IL PTEs the EMA MA grant date rather than the EMA MA notification date will be used. As a consequence, the PTE for Apixaban (Eliquis®) will expire in Israel two days earlier than would have been the case if the EMA MA notification date started the 14 year count. The IL Commissioner justified his decision by referring to the lack of uniformity between different European Patent Offices on this issue (i.e., whether the EMA grant date or the EMA notification date should be used to calculate the duration of SPCs under Article 13 of Regulation No 469/2009). However, the IL Commissioner was not apprised of the opinion of the ECJ advocate general (AG) in Seattle Genetics which was published prior to the decision in the Apixaban case. If the IL Commissioner had been apprised of the opinion of the AG, the Commissioner would have likely reached a different result.

In any event, after the CJEU published its binding decision in Seattle Genetics (case C-471/14) on October 6th, 2015, it was only a matter of time until the IL PTO would be called to reevaluate its position. In the matter of IL PTE petition for secukinumab (Cosentyx®), the IL PTO examiner initially calculated the IL PTE period based on the EMA grant date which was 4 days earlier than the notification date. The patentee argued that once the CJEU issued a final decision, which is applicable in all of the EU-5 Countries (among others), holding that the calculation of the duration of supplementary protection should be based on the EMA MA notification date – the IL PTO is bound to follow the CJEU determination. The IL PTO reevaluated its position and decided to follow the CJEU ruling, effectively canceling the IL Commissioner’ decision in the matter of IL PTE petition for Apixaban (Eliquis®).

Many thanks to Liad for sharing the news with us!

Merck's Gardasil extension request in Israel

Our friend and reader Michael Factor has just drawn my attention to a piece which he has posted on his IP Factor weblog, "A Request for a Patent Term Extension for IL 117459 “DNA ENCODING HUMAN PAPILLOMAVIRUS TYPE 18″ to Merck".  It's all about Gardasil, which has a lovely website of its own just here.

You can check Michael's post out for yourself here.

Gardasil: Israel draws closer to EU practice on combination products

Liad Whatstein (now practising as Liad Whatstein & Co) has just sent The SPC Blog the following report on an decision recently handed down by the Israeli Patent Office in connection with a patent term extension (PTE) for combination products. In essence the Israeli Patents Commissioner held that a patent claiming a single active ingredient was eligible for a PTE in connection with a combination product that comprised additional active ingredients. This decision, adds Liad, brings Israeli law in closer conformity with EU law in connection with SPCs for combination products. Writes Liad:

Gardasil is a quadrivalent vaccine comprising the proteins HPV18 L1, HPV16 L1, HPV11 L1 and HPV6 L1. Each of the four proteins in the vaccine protects against a separate strain of the Human Papilloma Virus (HPV). Merck's Israeli patent covers the HPV18 L1 protein and a composition comprising the protein. It does not specifically claim the other proteins included in Gardasil.

Under sections 64D(1) and 64A of the Israeli Patents Act, in order to be eligible for extension, the patent must claim the "material" ("the active ingredient in the medicinal product"). The Israeli PTO initially rejected Merck's PTE petition on the ground that the Israeli patent did not claim all the active ingredients in the product (i.e. there was no "match" between the scope of the patent and the "material").

The office's approach was in line with the approach taken in the past by several Patent Offices in Europe but was rejected by the Court of Justice of the European Union (CJEU) in Medeva and subsequently in Queensland & CSL which also related to Gardasil. It was also opposed to the traditional approach taken by the USPTO.

Merck appealed to Patents Commissioner. On 11 January 2015 the Commissioner overruled the decision and granted the PTE petition. In reaching his decision, the Commissioner noted that each protein in Gardasil was produced in separate fermentation and was a standalone API. Accordingly, the fact that HPV 18 L1 was combined with three other active ingredients in the product did not undermine the eligibility for patent term extension for the patent claiming a single protein.

Significantly, the Commissioner essentially adopted the patentee's approach solely based on analysis of the relevant statutory provisions and related Israeli case law, and completely disregarded the CJEU Medeva ruling. Nevertheless, the Commissioner's decision is an important precedent that brings Israeli law in closer conformity with EU law in connection with SPCs for combination products.

Generally, the Israeli Office is attentive to the legal situation and judicial developments in major jurisdictions. One exception is with respect to the peculiar and rather restrictive PTE system under Israeli law (for a short overview of these peculiarities see earlier SPC Blog post here). The Office has traditionally taken a restrictive approach in interpreting the PTE provisions, often resulting in denial of PTE eligibility. It is yet to be seen whether the recent decision may be a first step in the direction of more balanced decisions on patent term extensions.

Liad represented the patentee in the proceedings.

Israel's Commissioner acts on "wrongfully given bureaucratic decision" on Bazedoxifene

Michael Factor (of the IP Factor weblog) has drawn our attention to a recent blogpost of his own, here, on in Ruling Concerning Patent term extension to IL 120701 to Wyeth, 3 November 2014.  This is a somewhat strange tale involving Israel's recently amended patent law. In short, Wyeth filed a request to correct an error in the patent extension order for Bazedoxifene. The Commissioner for Patents did not allow the amendment but cancelled the patent term extension altogether as a "wrongfully given bureaucratic decision". Having established that it was null and void, he ordered that the patent term extension application be subjected to accelerated re-examination under the amended law.

Michael's post contains all the details.

Ezetimibe in Israel: a recent ruling on retroactive effect

There's a recent blogpost on Michael Factor's IP Factor weblog, "Israel Patent Office Shortens Patent term Extension for Ezetimibe", which provides a detailed analysis of Re 110956 Association of Israel Industrialists v Schering and Mercke, decided by Asa Kling on 18 September 2014. This ruling deals with, among other things, the retroactive effect of Israeli legislation on patent term.

Patent term extension in Israel: a recent ruling

It's always good to keep an eye on other weblogs, since they do feature patent term extension news from time to time. One such blog is Michael Factor's IP Factor blog, which has just posted a piece, "Israel Patent Number 94634, Extending and Shortening Patent Term Extensions", here, on The Association of Israeli Pharmacists v Sir Roy Calne and Wyeth, Ruling Asa Kling 13, July 2014.

The post is quite long and a bit complex, so we thank Michael for getting this case online while packing for his holiday.  That's enthusiasm for you!

Israel's Amendment No. 11 now imminent

From Liad Whatstein (Shlomo Cohen & Co) comes news of Amendment No. 11 of the Israeli Patents Act which, Liad tells us, is expected to be enacted shortly --as soon as next week, unless there is an unexpected delay.  The Amendment introduces several important revisions in the Israeli Patent Term Extension (PTE) system. Here's the firm's overview, from which the following is extracted for your interest:

The unique Israeli PTE system is based on “external” linkages to PTEs or SPCs granted in 21 “Recognized Countries” (US, EU-15 (Austria, Belgium, Denmark, Finland, France, Germany, Greece, Ireland, Italy, Luxembourg, the Netherlands, Portugal, Spain, Sweden and the United Kingdom), Australia, Iceland, Japan, Norway, and Switzerland). 

Eligibility to PTE and the calculation of the PTE period is based on multiple linkages: 

* The extension will be equal to the shortest extension granted to a Reference Patent in any of the Recognized Countries; 

* The PTE will expire no later than the first expiry date of a PTE of a Reference Patent in any of the Recognized Countries; 

* The extension must end no later than 14 years from the earliest date in which a regulatory approval was obtained in any of the Recognized Countries. 

* PTE in Israel will only be available if PTE/SPC was granted in the US and in at least one EU-15 country;

The result of these multiple linkages is that in most cases the de-facto extension period does not exceed two to three years. 

Amendment No. 11 of the Patents Act is the result of a bilateral agreement between Israel and the US. It has recently been approved by the Knesset (Israeli Parliament) Judiciary Committee and will be enacted shortly. 

Amendment No. 11 reduces the number of Recognized Countries to include only the US and the top five European markets (UK, France, Germany, Spain and Italy). It remains to be seen whether this reduction in the number of Recognized Countries will meaningfully extend in average Israeli PTEs.

Unfortunately, Amendment No. 11 also includes several provisions which further curtail the scope of PTE protection under Israeli law:

* An Israeli PTE will automatically expire when a Reference Patent is revoked or a PTE/SPC of a Reference Patent is revoked or withdrawn in any of the Recognized Countries; 

* If the basic term of the patent is about to expire and US/EU PTEs/SPCs have not yet been granted (i.e. no eligibility for PTE under the linkage mechanism), interim PTE orders will no longer be available; 

* Extensions of the deadline for filing the PTE petition (90 days after the date of regulatory approval in Israel) will not be granted; 

* Only one extension will be allowed during prosecution of the PTE petition; 

* A PTE petition must now be filed within 90 days of regulatory approval in Israel also if the patent application is still pending (previously, the deadline to file a PTE petition was extended until 90 days after patent grant); applicants will have a 90 days grace period from the date of the Amendment to file PTE petitions for pending patent applications. 

The pdf can also be downloaded here.

Thanks so much, Liad!

Re-revision of patent term extension in Israel

"Revision to the Israel Patent Law Revision Regarding Patent Term Extensions Revised Again" is a short blogpost by Michael Factor (the IP Factor) which you can read here. The blogpost is in English but the proposed amendment to the Israel Patent Law is in Hebrew only, here.

Circadin patent extended in Israel despite opposition

Neurim's conduct was found, on the facts,
not to be a "baa" to patent extension

"Unipharm Challenges Validity of Patent Term Extension for Neurim’s Circadin in Israel" is the title of this blogpost by Israeli patent attorney Michael Factor on his eponymous blog The IP Factor ("Opinionated Intellectual Property News Blog with an Israel Slant").

To cut a long story short (the full tale is there for all to read on Michael's weblog), Unipharm opposed the patent term extension of Neurim's Circadin patent and Commissioner King was required to consider three issues:

• Whether an extension could lawfully be granted on account of Neurim's inequitable behaviour 
• Whether the patent in question was to be considered the “basic patent” under Section 64a of Israel's Patent Law 
• Whether Circadin was the first drug containing the active ingredient as required by 64d of the Israel Law

The Commissioner rejected the opposition and extended the patent till 22 April 2017.  A large part of the IP Factor report deals with inequitable conduct, in particular the allegation that, in its ex parte application for patent extension, the company had behaved improperly and withheld or suppressed relevant information.  The Commissioner confirmed that an applicant was required to behave in an equitable manner, but did not consider that any breach by Neurim of that requirement was sufficient to prevent the extension.

Patent term extension: to err is human

Hot off the press is this commentary by Israeli patent practitioner Michael Factor (Factor Patent Attorneys) on this week's Israeli decision in Patent Term Extension for 154325 submitted by Reinhold Cohen Patent Attorneys and Gilat Bareket Lawyers on behalf of Centocor Ortho Biotech Inc., before Jaqueline Bracha, Deputy Commissioner, 22 March 2012. Its contents will make uncomfortable reading for many a patent practitioner in private practice.

 As Michael -- not a man to pull his punches -- comments:

"From the affidavits submitted by employees of the agents for applicant ... it is clear that despite the firm being organized and having procedures in place to cover patent term extensions, there was human error. The deadline was missed and this was discovered seven months later.

Whether this is or is not fairly described as ‘unintentional’ or as the agent for applicant exhibiting ‘due care’, such circumstances cannot fairly be described as ‘circumstances over which the applicant and his representative had no control and which could not be prevented‘ unless one rules that human error is unavoidable. There was no earthquake or natural disaster to blame, there was no war, nor was there a postal strike. A paralegal and her supervisor both messed up. It happens ...".

Following the decision of the Deputy Commissioner in favour of the patent proprietor, Michael suspects that generic companies Teva or Unipharm might be considering an appeal.

Israel refuses escitalopram SPC

In April the SPC Blog published news of the invalidity of Lundbeck's escitalopram patent and SPC in the Netherlands (see also IPKat post here). Now, via Jeffrey Boone (Covidien), comes information of the fate of escitalopram in Israel, thanks to a newsletter article by the Reinhold Cohn Group. According to that firm,

"... The Israeli Patent office recently refused H. Lundbeck's application to extend the term of its Israeli patent, covering its blockbuster drug Cipralex® whose active pharmaceutical ingredient is the single (S)-enantiomer (escitalopram) of the racemate Citalopram. The refusal was based on the Israeli Registrar's conclusion that the first registration of a drug containing escitalopram by the Israeli Ministry of Health was the previous registration of the racemate (Citalopram, marketed as Cipramil®)".

The newsletter article then goes on to analyse the Patent Office decision which, it concludes, was erroneous.