Pregabalin – Australia

On Feb 15, 2017,  Judge Nicholas J of Australian Federal Court has delivered decision in Apotex Pty Ltd v Warner-Lambert Company LLC (No 3) [2017] FCA 94 for the drug Lyrica ® (Pregabalin). The Australian Federal Court held that applying for Pharmaceutical Benefits Scheme (PBS) listing does not exploit a patent and it is not an infringement.

In October 2016, the Federal Court upheld the validity of all the claims of Patent No. 714980 (set to expire on Jul 16, 2017) in a challenge brought by Apotex Pty Ltd. The claims are directed to methods of treating pain using compounds including pregabalin.  The present judgement considers, amongst other matters, the form of injunctive relief to which Pfizer is entitled. Pfizer submitted that applying for PBS listing constitutes an infringement of the patent and sought an injunction to prevent Apotex from doing so before the expiry of the patent.

In this case, Apotex proposed to take steps during the patent term to apply for PBS listing for its generic pregabalin products, so that it was in a position to commence offering them for sale at subsidised prices under the PBS scheme once the patent expired.

Justice Nicholas characterized an application for PBS listing as a ‘mere preparatory step’ which may enable a generic supplier to exploit the invention after the expiry of the patent, without amounting to an ‘offer’ to sell or dispose of its products. Justice Nicholas also indicated that other preparatory steps taken by a generic supplier in anticipation of launch would not infringe a patent. Justice Nicholas accepted that an offer for sale during the patent term could amount to an act of exploitation even though the products would not be supplied until after patent expiry, and also noted that the word ‘offer’ should be construed broadly such that it could encompass an expression of a willingness to sell.

Hydrocodone – USA

On Feb 22, 2017, District court of Delaware decided in favor of Reco/Pernix on Zohydro (Hydrocodone ER capsule) patents and found that Actavis' proposed generic products infringe claims of U.S. Patent   No. · 9, 13 2, 096 ("the '096 patent") and U.S. Patent No. 6,902,742 ("the '742 patent").

Zohydro® ER extended-release capsules contain hydrocodone bitartrate and are indicated "for the management of pain severe enough to require daily, around-the-clock, longterm opioid treatment and for which alternative treatment options are inadequate." Recro licenses the '742 and '096 patents to Pernix Therapeutics Holdings, Inc. ("Pernix") and Pernix markets and sells Zohydro® ER capsules in the United States.

Patented claims require a permeable or semi-permeable coating selected from the group consisting of an ammonio methacrylate copolymer, a methacrylic acid copolymer and a mixture thereof.  Actavis uses Ethyl cellulose in its formulation. Actavis maintains that Recro dedicated ethylcellulose to the public because cellulosic polymers were disclosed in the specification, but not claimed. Disclosure dedication occurs when the patentee "discloses but declines to claim subject matter”.

The court however found that a person skilled in the art would not have been able to clearly identify that ethylcellulose was disclosed and not claimed, given the generality of the phrase "cellulosic polymers". The court finds, therefore, that ethylcellulose was not dedicated to the public.

Ethylcellulose provides same function by same way to have same result in comparison to claimed polymer. The specification of the '096 patent explicitly states that the functions of the placebo bead coating are to "provide a physical barrier essentially separating or sequestering the gelling agent from the other components of the composition" and to "control (i.e. delay or otherwise limit) the ingress of water into the second bead population, thus restraining the gelling action of the gelling agent."

In sum, the court finds infringement of all of the asserted claims of the '096 and '742 patents.

Palonosetron – USA

On Feb 14, 2017, A New Jersey federal judge found that Dr. Reddy’s Laboratories Inc.’s palonosetron product infringed patents on Helsinn Healthcare SA’s anti-nausea drug (Aloxi) and rejected Dr. Reddy’s contention that two of those patents are invalid.

DRL submitted NDA No. 203050 to the FDA pursuant to the Hatch-Waxman Act, 21 U.S.C. § 505(b)(2), seeking approval to market its own palonosetron product. The patents covered by DRL’s Paragraph IV certifications include U.S. Patent Nos. 7,947,724 (“the ’724 patent”); 8,729,094 (“the ’094 patent”); and 9,066,980 (“the ’980 patent”). Helsinn contends that DRL’s Accused Product infringes thirteen claims in the Asserted Patents. DRL has raised the defense of non-infringement for three of those claims and argues that the other ten are invalid.

Infringement

DRL’s Accused Product contains sodium acetate trihydrate and it asserted that it idoes not fall under the definition of chelating agent. Claim construction construed the term “chelating agent” to mean a “multidentate ligand that can form a ring structure by reacting with a metal ion. The court based on a review of all of the evidence presented at trial, and as reflected in the findings of fact above, concluded that Helsinn proved by a preponderance of the evidence that the acetate present in DRL’s product is a multidentate ligand that can form a ring structure by reacting with a metal ion. Accordingly, the Accused Product contains a “chelating agent”.

Invalidation

DRL raised Enablement and Written Description grounds for invalidity. On enablement court said that weighing the relevant Wands factors, we conclude that the totality of this evidence does not support a finding that undue experimentation would be necessary to practice the asserted claims. On Written Description ground court said that we have considered the arguments and evidence presented by DRL and the countervailing arguments and evidence by Helsinn, and find that Helsinn’s evidence is more persuasive on the matter of written description.

Therefore we conclude that DRL has failed to meet its burden of demonstrating, by clear and convincing evidence, that the asserted claims are invalid for lack of enablement or lack of written description.

Saxagliptin - USA

On Feb 2, 2017, Judge Gregory Sleet of the U.S. District Court for the District of Delaware issued a decision in favor of AstraZeneca on a compound patent for saxagliptin expiring in Jul 2023..

AstraZeneca is involved in patent infringement litigation against several ANDA filers that are seeking FDA approval to market generic versions of Onglyza (saxagliptin hydrochloride). The key patent protecting Onglyza is U.S. Patent No. RE44,186 (set to expire July 31, 2023).

Judge Gregory Sleet presided over a trial in September 2016 involving most of the ANDA filers (Amneal, Aurobindo, Mylan, and Teva). At trial, the ANDA filers conceded that the RE’186 patent covers their proposed generic tablets, but they asserted that the patent is invalid due to obviousness over lead compound Vildagliptin. 

Judge Sleet determined that, even if vildagliptin were selected as a lead compound, the ANDA filers failed to prove by “clear and convincing” evidence that modifying vildagliptin to yield saxagliptin would have been obvious. He explained, for example, that the ANDA filers failed to show a motivation to move the hydroxadamantyl group of vildagliptin with any reasonable expectation of success based on the limited structural information on moving from N-linkage to C-linkage, the existence of sufficiently potent compounds, and the inconsistency with an established solution to the stability problem.

Parallel IPR petitions have been filed for this RE'186 patent by few ANDA filers. Patent Office held a hearing in the IPR proceedings on Jan 25, 2017 and is expected to issue its decision on the validity of the RE’186 patent by May 2, 2017.

Dasatinib - EU

On Feb 1, 2017, the EPO’s Technical Board of Appeal announced that it rejected BMS’s appeal and revoked the EP1169038 patent.

European Patent EP'038 (set to expire in April 2020, with SPC until November 2021) covers dasatinib as a compound per se. Actavis, Apotex, Mylan, and an anonymous party initiated opposition proceedings in the European Patent Office (EPO) seeking the revocation of the ’038 patent. In January 2016, the EPO’s Opposition Division issued a decision revoking the ’038 patent.

Bristol-Myers Squibb (BMS) appealed. BMS asserted that the Opposition Division misapplied the legal requirements to prove insufficiency of disclosure and lack of inventive step. BMS also asserted that the Opposition Division erred by failing to consider evidence of dasatinib’s benefits published after the filing of the BMS’s patent application.After deliberation, the Technical Board of Appeal announced that it dismissed BMS’s appeal and revoked the ’038 patent due to lack of inventive step.

Dasatinib was granted approval by EMA in Nov. 2006 for the treatment of:

1. Newly diagnosed Philadelphia-chromosome-positive (Ph+) chronic myelogenous leukaemia (CML) in the chronic phase

2. Chronic, accelerated or blast phase CML with resistance or intolerance to prior therapy including imatinib mesilate;

3. Ph+ acute lymphoblastic leukaemia (ALL) and lymphoid blast CML with resistance or intolerance to prior therapy.

Market exclusivity & orphan drug exclusivity expired in Nov. 2016. BMS has submitted to the European Medicines Agency on 17 January 2013 an application for modification of the agreed paediatric investigation plan (PIP) with a deferral and a waiver for CML & ALL indications. The Paediatric Committee has agreed to changes to the paediatric investigation plan. This may result in extension of orphan drug exclusivity till Nov. 2018 (additional 2 years because of PIP). 

BMS owns another patent  EP1610780 (set to expire on March 23, 2024) that covers method of using dasatinib for various cancer including CML. In October 2012, the Opposition Division decided to revoke the ’780 patent due to insufficiency of disclosure. BMS appealed the ’780 patent’s revocation. The Board of Appeal has scheduled a hearing to decide the appeal for Friday, February 3, 2017.

There is another patent EP1711481 (set to expire on February 4, 2025) covers a monohydrate polymorph of dasatinib. The ’481 patent as amended, withstood opposition proceedings initiated by Apotex and an anonymous party.

Tenofovir & Emtricitabine - UK

On Jan 13, 2017, in his decision in “Teva UK Limited and Others v Gilead Sciences Inc” Arnold J has again referred a question to the CJEU concerning the interpretation of Article 3(a) of Regulation 469/2009 (the “SPC Regulation”) namely: what are the criteria for deciding whether a product (active ingredient or combination of active ingredients) is “protected” by a basic patent in force?

Teva, Accord, Lupin and Generics UK ltd commenced invalidity proceedings against one of Gilead’s SPCs. The SPC is for a composition containing tenofovir disoproxil with emtricitabine. Gilead’s combination product is TRUVADA® - an anti-retroviral used in treating HIV.

Gilead’s SPC relies on the marketing authorisation for Truvada and EP 0 915 894 (“the Patent”), claim 27 of which reads as follows:

“A pharmaceutical composition comprising a compound according to any one of claims 1-25 together with a pharmaceutically acceptable carrier and optionally other therapeutic ingredients”.

Claimants argued that the case law is clear enough and no reference to the CJEU was needed and, in any event, emtricitabine is not “specified” in claim 27. Gilead in response argued that its SPC complies with the SPC Regulation as it is enough that its product falls within the scope of one of the basic patent’s claims using the “extent of protection” rules.

Arnold J decided that the infringement test for Art 3(a) had clearly been rejected but also came to the conclusion that “it is not sufficient for the product in question to fall within the scope of protection of the basic patent applying the Extent of Protection Rules. Something more is required”. His conclusion was therefore that “the test to be applied in order to determine whether a product is “protected” by a basic patent within the meaning of Article 3(a) remains unclear”, which necessitated a referral to the CJEU.

Paclitaxel - UK

Abraxis had appealed against the decision dated Aug 26, 2016 of refusal by the UK Intellectual Property Office (UK IPO) to grant an SPC covering Abraxis’ nab-paclitaxel product, Abraxane™. Abraxane is a new formulation of the known medicine, paclitaxel, and includes paclitaxel formulated as albumin bound nanoparticles (referred to by Abraxis as nab-paclitaxel).

Arnold J (High Court of England and Wales) in his decision on Jan 13, 2017 has made a further referral to the CJEU, this time concerning the interpretation of Article 3(d) of Regulation 469/2009 (the “SPC Regulation”), namely: “Is Article 3(d) of the SPC Regulation to be interpreted as permitting the grant of an SPC where the marketing authorisation referred to in Article 3(b) is the first authorisation within the scope of the basic patent to place the product on the market as a medicinal product and where the product is a new formulation of an old active ingredient?”

Arnold J in his analysis considered that it was clear that paclitaxel and not nab-paclitaxel was the active ingredient for the purposes of Art 1(b). However, in relation to Art 3(d), Arnold J did not consider it clear whether new formulations could be awarded an SPC. Abraxis accepted that the facts of Neurim case relate only to the award of SPCs for new therapeutic uses of old active ingredients, but argued that Neurim could also apply to new formulations of old active ingredients. Arnold J therefore stated he would refer the question set out above to the CJEU.

Mometasone furoate - USA

On Jan 30, 2017, Judge Sue Robinson of the U.S. District Court for the District of Delaware issued a decision in favor of Amneal and declared that Merck’s 2018 patent does not cover Amneal’s proposed generic (mometasone furoate) nasal spray.

Nasonex (mometasone furoate) is a corticosteroid that is approved in the form of a 50 mcg metered-dose, manual-pump nasal spray. Various companies have filed ANDAs with Paragraph IV certifications seeking FDA approval to market generic mometasone furoate nasal sprays prior to the expiration of Merck’s U.S. Patent No. 6,127,353 (set to expire on October 3, 2017, with pediatric exclusivity until April 3, 2018). The ’353 patent covers the monohydrate crystalline form of mometasone furoate.

Merck was also involved in patent infringement litigation with Apotex (FTF) and Teva previously. The courts ultimately determined that the ’353 patent does not cover Apotex’s & Teva’s generic nasal spray.

Merck has appealed the decision in Teva's case and most likely would appeal this decision also to the U.S. Court of Appeals for the Federal Circuit.

Glatiramer acetate - USA

On Jan 30, 2017, Judge Gregory M. Sleet of the U.S. District Court for the District of Delaware declared that four of Teva’s 2030 method-of-use patents are invalid due to “obviousness.” Teva continues to pursue patent infringement litigation against the ANDA filers based on a fifth 2030 method-of-use patent, as well as a 2035 manufacturing process patent.

Teva is involved in patent infringement litigation against competitors that have filed ANDAs with Paragraph IV certifications seeking FDA approval for generic versions of Copaxone (glatiramer acetate) 40 mg/mL pre-filled syringes. There are five patents listed in the Orange Book for Copaxone 40 mg/mL: U.S. Patent Nos. 8,232,250; 8,399,413; 8,969,302; 9,155,776; and 9,402,874 (all set to expire on August 19, 2030). Sandoz, Amneal, Dr. Reddy’s, Mylan (in partnership with Natco), and Synthon submitted ANDAs with Paragraph IV certifications challenging the OB patents.

Judge Sleet issued a decision in favor of the ANDA filers. More specifically, Judge Sleet agreed with the ANDA filers that the ’250, ’413, ’302, and ’776 patents are invalid due to obviousness. In an opinion explaining his decision, Judge Sleet was not impressed by Teva’s patents: “The court sees the ’250, ’413, ’302, and ’776 patents as nothing more than ‘life-cycle management’--an attempt to continue to monopolize a multi-billion dollar market for a blockbuster drug.”

Teva may appeal this decision to the U.S. Court of Appeals for the Federal Circuit.

Pregabalin - France

On Dec 02, 2016, the Court of First Instance of Paris rendered a decision in permanent injunction case in Pregabalin (Lyrica), initiated by Warner-Lambert (the patentee) and licensees Pfizer against 9 groups of generic companies (the defendants).

All defendants are on the market with marketing authorizations which comprise the two open indications (epilepsy and generalized anxiety disorders), but do not comprise the still-patented indication (a specific type of pain).

WARNER LAMBERT asserts that the defendant companies would commit infringement by supply of means by knowingly and in bad faith marketing generic Pregabalin as a proprietary medicine protected by patent EP0934061 for pain indication. The majority of the pregabalin products are prescribed for the pain indication (83.8% of the sales in France, according to the patentee).

The defendant companies respond that WARNER LAMBERT cannot collectively criticise them for infringement by supply of means, that it must prove for each defendant, commission of the criticised acts, which it fails to do, that they have complied with all prescriptions on limiting sales of Pregabalin exclusively to those indications for which they have obtained a market authorisation, specifying said specialisms on the instructions for use enclosed with the product and that they have informed municipal and hospital pharmacists and physicians that Pregabalin may not be substituted when used to treat neuropathic pain.

The decision is interesting on many aspects covering skinny label, second medical use claims and contributory infringement.

First, the decision confirms that Swiss type claims, as the ones of the opposed patent (use of pregabalin for the preparation of a pharmaceutical composition to treat pain) are to be considered as process claims, and not product claims and the medicines are not manufactured in France, there can be no direct infringement.

Second, contributory infringement was dismissed for two main reasons: not only the marketing authorizations were limited to the two indications in the public domain, but above all there has been a widely spread information to relevant health professionals about the specificities of the generic pregabalin launched.

Third, the request of the patentee was considered unlawful. The patentee requested to jointly forbid all defendants to sell more than 16.2% of the pregabalin market (representing the market share of the public domain indications in France), as well as to summon defendants to share with him information allowing to understand the origin and the distribution channels of the products.