Current State of Data Protection and Exclusivity in Russia

The BRIC Wall Blog is pleased to present the following guest post by Ivan Burkov, Ph.D.

It has been 3.5 years since Russia joined the World Trade Organization (WTO) and implemented the right of data exclusivity for innovative pharmaceutical products. In this short period of time, the definition of data exclusivity has changed and precedent setting litigation has ensued. In this post, I attempt to delineate the most important events to date regarding data exclusivity in Russia and evaluate its protective potential.

Background

Article 39.3 of the Agreement on Trade-Related Aspects of Intellectual Property Rights (TRIPS) specifies that the members of the WTO shall take the necessary steps to ensure the protection of undisclosed proprietary data submitted to obtain the registration of a pharmaceutical product, the origination of which involved considerable effort.

Upon accession to the WTO, Russia documented its agreement to ensure the protection of undisclosed information and test data in paragraph 2 of the Protocol of Accession of the Russian Federation to the WTO. The right of data exclusivity became effective on August 22, 2012, the official date of Russian Federation accession to the WTO. The concept was later introduced into the article 18 of Federal law № 61-FZ “On the Turnover of Medicines”, a central law for pharmaceutical industry in Russia. According to this new law, data exclusivity was defined as follows:

Receipt, disclosure and use for commercial purposes and for the purposes of medicine state registration of the information of the results of preclinical and clinical studies provided by an applicant for the registration of the medicine is not permitted without the applicant’s consent during 6 years from the date of the medicine state registration.

Concept evolution 

The original definition of data exclusivity did not specify the type of protected medicine (whether the medicine had to be an original/first-ever registered medicine or something else) or how the term was to be split between registration (data) exclusivity and market exclusivity. Since implementation of data exclusivity in 2012, the concept has been actively discussed by the industry players, law firms and other interested parties, and most stakeholders agree that data exclusivity protection alters Russian market attractiveness in the eyes of innovative medicines producers. However, no specific court cases had been instituted and it was not known whether any company had successfully used the right of data exclusivity to protect its product(s) from generic competition (as information regarding extrajudicial dispute resolution procedures was not publically available).

On December 22, 2014, the Russian president signed Federal law № 429-FZ, which introduced certain amendments to the Federal law № 61-FZ “On Circulation of Medicines”. One of the amendments (the effective date of which is January 1, 2016) affects data exclusivity. As a result, beginning January 1, 2016, data exclusivity will be defined as follows:

It is not permitted to use for the commercial purposes the results of pre-clinical trials of medicinal products and clinical trials of medicines, provided by the applicant for state registration of the medicine without his consent for the period of six years from the date of state registration of the reference medicine in the Russian Federation.

Compared to the original definition, the new definition limits the opportunities in which pre-clinical and clinical trial data are eligible for protection. Specifically, their use is prohibited for commercial purposes only. Additionally, data exclusivity is now granted to reference medicines, where a reference medicine is defined as:

 …a medicine which previously has never been registered in Russia, whose quality, efficacy and safety have been confirmed by the results of pre-clinical and clinical trials and which is used for the assessment of bioequivalence or therapeutic equivalence, quality, efficacy and safety of a generic (biosimilar) medicine.

The amendments also specify a division of the six year term between registration* (what is often referred to as “data” exclusivity in other jurisdictions) and market exclusivity: four (registration exclusivity) plus two (market exclusivity) years for generic drugs and three (registration exclusivity) plus three (market exclusivity) years for biosimilars.

* Registration exclusivity is determined from the date of registration of a reference medicine and prohibits a generic/biosimilar applicant from using the protected data of the originator for the purpose of seeking a state registration.

Russian company fights off Novartis in data exclusivity dispute

Early in 2015, Russia saw its very first court case involving data exclusivity. Specifically, Novartis Pharma AG (Novartis) claimed that local company Biointegrator LLC (Biointegrator) violated the prohibition against using Novartis’ preclinical and clinical data during state registration of its product “Nescler”, a generic version of Novartis’ fingolimod (sold under the brand name Gilenya®). Gilenya® is approved for the treatment of relapsing-remitting forms of multiple sclerosis in adults. In the suit, Novartis asked the court to cancel Biointegrator’s state registration.

Instead of focusing on the data exclusivity issue itself, the semantic vector of the case shifted towards determining the actual timing of the submission of the generic dossier. Biointegrator argued that cancellation of the registration was not appropriate because the application for state registration of “Nescler” had been submitted by another company (on April 2, 2012) prior to the date of implementation of data exclusivity provisions (August 22, 2012). Subsequent to these events, ownership rights were transferred from the other company to Biointegrator pursuant to a commercial agreement. In view of these facts, the court of first instance agreed with Biointegrator and rejected Novartis’ request for cancellation.

Undeterred, Novartis appealed. The appeal court held that an application for registration of a generic product submitted by another company did not exempt Biointegrator from liability since the generic company’s abbreviated clinical development (bioequivalence studies) relied on Novartis’ protected data and was initiated after the implementation of the data exclusivity provisions. As a result, the court agreed with Novartis’ arguments and canceled the marketing authorization of the generic product.

Unhappy with the appeal court’s decision, Biointegrator appealed to the court on intellectual rights (Intellectual Rights Court), which ruled for Biointegrator and restored the decision of the first instance court, allowing the generic product to return to the market. The arguments of the Intellectual Rights Court in holding for Biointegrator were as follows.

First, both parties agreed that Biointegrator was liable to follow the corresponding provisions of the Federal law, since the state registration application for “Nescler” was submitted after the date when the provisions for data exclusivity concept became effective. Nonetheless, the panel of judges did not agree with the appeal court that Biointegrator had used Novartis’ protected data, holding that the decision was made in violation of substantive norms. Specifically, the Intellectual Rights Court held that the appeal court incorrectly concluded that the right of data exclusivity covered any information relating to the preclinical and clinical trials of the original medicine. More specifically, according to the Intellectual Rights Court, the Federal law “On Circulation of Medicines” provides for a fast-track registration procedure for generic medicines. It requires that information on the clinical trials of an original medicine be published in specialized sources (namely, scientific journals, etc.) and that documented results of a generic’s bioequivalence/therapeutic equivalence studies be provided. Moreover, the court stated that the “…systematic interpretation of the provisions on data exclusivity suggests that the specified prohibition does not apply to publically available information, including scientific publications, and legislator recognizes the use of such information legitimate”.

The Intellectual Rights Court determined that the effectiveness of the generic product in the treatment of multiple sclerosis was based on information contained in previously published articles describing the results of clinical trials involving Gilenya® (specifically, the articles entitled “A Placebo-Controlled Trial of Oral Fingolimod in Relapsing Multiple Sclerosis” and “Oral Fingolimod or Intramuscular Interferon for Relapsing Multiple Sclerosis”). At the same time, the definition of data exclusivity under the Federal law “On Circulation of Medicines” prohibited the use of the “results of pre-clinical trials of medicinal products and clinical trials of medicines, provided by the applicant for state registration of the medicine. Unfortunately, Novartis was unable to prove that Biointegrator used undisclosed data from Gilenya®’s registration dossier, which led to the unfavorable decision by the Intellectual Rights Court.

Impact on the industry 

Data exclusivity and intellectual property protection in general are essential for the pharmaceutical industry, where extremely large sums of money are invested in developing highly risky health care solutions. At the same time, maintaining the transparency of clinical trial data is of great significance and is expected by patients, healthcare providers, companies and health authorities around the world. For example, the European Medicines Agency (EMA) bases its scientific opinions on the results of clinical trials carried out and submitted by pharmaceutical companies. Since January 1, 2015, the EMA has been proactive publishing clinical reports submitted as part of marketing-authorization applications for human medicines.

The Novartis case demonstrates that Russian authorities treat the right of data exclusivity only in connection with undisclosed, non-public information of the results of preclinical and clinical trials of an original medicine. Thus far, a very limited number of original medicines have undergone their first-ever clinical development in Russia. Rather, in most of the cases, information on the clinical trials for a medicine is already publically available from a number of sources at the time the originator seeks local registration in Russia. Therefore, the Novartis case may open the way for generic companies to bypass the legal right of originators to protect its data.

Although the Novartis case has its own unique set of facts and stare decisis is not officially practiced in Russia, innovative companies should take note of this case and its implications as an additional risk for their original products in the Russian market. At the end of the day and in the long term, the lack of intellectual property protection in Russia may affect generic producers themselves, as the attractiveness of a market which does not guarantee sufficient protection for innovators will decrease.

This post was edited by Lisa Mueller.

This article is intended to provide general information about the subject matter. Professional legal advice should be sought about specific circumstances. The opinions expressed herein are those of the author. Comments or questions on this article can be addressed to the author (vanyaburkov@gmail.com) or Lisa Mueller (llmueller@michaelbest.com).

Merck’s Ezetrol and Patent Term Extension in Israel

Patent Term Extension in Israel 

Under Israeli Patents Act (Patents Act), a petition for patent term extension (PTE) must be submitted no later than 90 days from the date of regulatory approval of a drug. However, patent term extension is available only for a “basic” patent. A basic patent is a patent that protects a pharmaceutical compound (API), a process for making the API, use of an API or a pharmaceutical product containing an API, a process for making a pharmaceutical compound containing the API or a medical device that requires regulatory approval in Israel. As a result of such a broad definition, a number of patents may cover a product for which PTE is sought. As a result, each of these patents may qualify as a “basic” patent. While a patentee can select which basic patent to extend, only one basic patent can be extended for each product.

The Israeli Patent Office will extend the term of protection of a basic patent if the following conditions are met:

  1. A PTE petition is filed in good faith;
  2. The API, the process of its manufacture, its use, the pharmaceutical composition containing the API, or the medical device are claimed in the basic patent and the basic patent is in force;
  3. The pharmaceutical composition is registered according to the Pharmacists’ Ordinance;
  4. The registration is “the first regulatory approval permitting use of the compound in Israel for pharmaceutical purposes”;
  5. If a pharmaceutical composition is registered in the U.S., a PTE in Israel will only be available if a “patent of reference” was also extended in the U.S. A “patent of reference” is any patent that protects the pharmaceutical product or medical device claimed in a “basic” Israeli Patent, regardless of whether or not it corresponds to the basic Israeli Patent; and
  6. If a pharmaceutical composition is registered in any of the countries listed in Part B of the Addendum (namely, Italy, Britain, Germany, Spain and France), a PTE in Israel will only be available if a “patent of reference” has been extended in at least one of these countries.

The PTE period is calculated according to the following guidelines:

  1. The period of extension will not exceed five years;
  2. The overall period of the patent and 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 (namely, U.S., Italy, UK, Germany, Spain and France);
  3. The period of extension will be equal to the shortest period of extension granted to a “reference” patent in any of the recognized countries; and
  4. Regardless, a PTE will expire no later than the first expiry date of a PTE of any “reference” patent in any of the recognized countries.

In Israel, the main principle is that a PTE will be granted for a period equal to the shortest duration of a PTE granted in any recognized countries. In addition, the extension period cannot exceed five years and the overall patent and extension period cannot exceed 14 years from the date of the earliest regulatory approval in any of the recognized countries.

Israeli Patent No. 110956 

Israeli Patent No. 110956 (‘956 patent) covers Merck’s drug Ezetrol ((3R,4S)-1-(4-fluorophenyl)-3-[(3S)-3-(4-fluorophenyl)-3-hydroxypropyl]-4-(4-hydroxyphenyl)azetidin-2-one), a cholesterol lowering drug. In many parts of the world, Ezetrol is marketed as Zetia.

The ‘956 patent was initially extended for a period of 1,014 days pursuant to Amendment No. 3 of the Patents Act. Under Amendment No. 3 the Israeli PTE was not linked to the shortest PTE or SPC in reference countries but to the PTE or SPC elected by the patentee. Amendment No. 7 introduced for the first time the mechanism which calls for linkage to the shortest PTE/SPC in reference countries. According to Amendment No. 7, the duration of the Israeli PTE order was linked to the shortest PTE/SPC period (meaning the number of days of extension) and to the expiration date of any PTE/SPC in a Recognized Country. The Association of Generic Manufacturers (Association) petitioned to shorten the PTE period according to Amendment No. 7 of the Patents Act. Specifically, the Association argued that according to the transitional provisions, Amendment No. 7 applied retrospectively in connection with PTE orders entered before this amendment came into force.

The Commissioner granted the Association’s petition. Specifically, the Commissioner linked the PTE period of the‘956 patent to the period of the U.S. PTE and shortened the PTE period to 496 days (which was the U.S. PTE period) instead of 1,014 days (the original PTE period). The “reference” U.S. PTE was granted approximately one year after the grant of the Israeli PTE.

Merck challenged the constitutionality of the transitional provisions applying Amendment No. 7 retrospectively. The District Court rejected Merck’s arguments. Nonetheless, the court granted Merck’s alternative basis for the appeal. Based on the legislative history and the language of the statute, Merck distinguished between linkage to the PTE period (number of days) and linkage to the expiry date of the reference PTE/SPC. Specifically, Merck argued:

  1. With respect to the linkage to the PTE period, only a reference PTE/SPC already granted at the date of grant of the Israel PTE will be eligible to shorten the PTE period; and
  2. With respect to the linkage to the expiration date, any reference PTE/SPC will count, regardless of whether it is granted before or after the grant of the IL PTE.

The court agreed this interpretation. As a result, the U.S. PTE order (granted after the Israeli PTE) was no longer relevant and the Israeli PTE was extended by additional 9 months (based on linkage to the German PTE).

The court’s decision that the period of the Israel PTE could only be linked to the period of a reference PTE/SPC granted until the grant date of the Israeli PTE could have important consequences.

Please continue to watch the BRIC Wall Blog for updates on PTE in Israeli.

This post was written by Lisa Mueller and Liad Whatsein of Liad Whatstein & Co.

Biologics and Biosimilars Bits and Bytes – December 10, 2015

Amgen files for first European Approval of a Biosimilar to Humira®

On December 4, 2015, Amgen Inc. (Amgen) announced the filing of a Marketing Authorization Application (MAA) with the European Medicines Agency (EMA) for ABP 501, a biosimilar version of AbbVie Inc.’s (AbbVie) Humira® (adalimumab). According to Amgen, its MAA submission included analytical, clinical and pharmacokinetic data. Amgen conducted Phase 3 comparative efficacy and safety studies in both moderate-to-severe plaque psoriasis and moderate-to-severe rheumatoid arthritis patients. Amgen indicated that its Phase 3 studies met their primary endpoints showing clinical equivalence to Humira®. The safety and immunogenicity of ABP 501 was also comparable to Humira®. Additionally, data to support the transition of Humira® patients to ABP 501 was also included in the filing.

This MAA filing follows Amgen’s November 25, 2015 filing of a 351(k) application with the U.S. Food and Drug Administration (FDA) for ABP 501.

Coherus Files Two New IPR Petitions against AbbVie’s Patents Covering Humira®

On December 7, 2015, Coherus Biosciences Inc. (Coherus) filed two new IPR petitions, IPR2016-00188 and IPR2016-00189, against AbbVie’s U.S. Patent Nos. 9,017,680 and 9,073,987 covering Humira®. These filings come almost a month after the November 9th filing by Coherus of IPR petition, IPR2016-00172, against another AbbVie patent covering Humira®, U.S. Patent No. 8,889,135. Coherus’ three IPR petitions can be found here: 1. IPR201600188 2. IPR201600189 3. IPR201600172. This brings the total number of IPR petitions filed against AbbVie patents covering Humira® to five. Earlier this year, on June 26, 2015 Amgen filed IPR petitions, IPR2015-01514 and IPR2015-01517 against two other AbbVie patents, U.S. Patent Nos. 8,916,157 and 8,916,158.

Infliximab Biosimilar Approved in Korea

On December 4, 2015, Samsung Bioepis Co., Ltd., (Samsung Bioepis) announced that Korea’s Ministry of Food and Drug Safety (MFDS) approved Renflexis®, a biosimilar version of Remicade® (infliximab), also known as SB2. Renflexis® was approved for the treatment of rheumatoid arthritis, ankylosing spondylitis, Crohn’s disease, pediatric Crohn’s disease, ulcerative colitis, pediatric ulcerative colitis, psoriatic arthritis and plaque psoriasis. This is the second biosimilar approved in Korea for Samsung Bioepsis, a joint venture between Biogen and Samsung Biologics. The first approval was in September 2015 for Brenzys®, a biosimilar version of Enbrel® (etanercept), also known as SB4.

In February 2013, Samsung Bioepis and Merck & Co. (Merck) announced a development and commercialization agreement under which Merck would commercialize multiple pre-specified and undisclosed biosimilar products in certain partnered territories. Under terms of the agreement, Samsung Bioepis was responsible for preclinical and clinical development, process development and manufacturing, clinical trials and regulatory registration. Merck was responsible for commercialization. As a result, Merck will commercialize Renflexis® in South Korea and plans to launch in the first half of 2016.

This post was written by Lisa Mueller.