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.

Rivastigmine - UK

On Dec 21, 2016, the court of appeal (UK) in Novartis Ag v Focus Pharmaceuticals UK Ltd upheld the Arnold J’s decision on added matter and obviousness.

In these actions the claimants (“Novartis”) alleged that the defendants (“Focus” and “Actavis” in action HP-2013-000011 and “Teva” in action HP-2013-000012) had infringed European Patent (UK) No. 2,292,219 entitled “Transdermal therapeutic system for the administration of rivastigmine”. The defendants denied infringement and counterclaimed for revocation of the Patent on the grounds of added matter, obviousness and insufficiency. 

Arnold J in his judgment, handed down on 27 April 2015 [2015] EWHC 1068 (Pat), found that the Patent lacked inventive step over a single piece of prior art, US Patent No. 6,335,031 (“US 031”), and was also invalid for added matter.  He rejected the allegation of insufficiency.  He also held that if the Patent had been valid, the defendants would have infringed it. Novartis appealed the order revoking the Patent.

On appeal, Kitchin LJ, delivering the judgement of the Court upheld Arnold J’s decision on added matter and obviousness. T appeal he Court concluded that even if the judge at first instance had erred in failing to consider the teaching of the prior art as a whole and in the light of the common general knowledge, the judge was correct to conclude that it would have been obvious to try to administer the starting dose specified in the Patent in a small-scale clinical trial, because the skilled team would think it had a reasonable prospect of success in light of the food effect and the release profile of a transdermal patch.

Tiotropium - UK

On Dec 16, 2016, the court of appeal (UK) denied the application by Boehringer Ingelheim Pharma GmbH & Co (Boehringer) seeking permission of the Court of Appeal to appeal a decision by Morgan J to revoke Patent (UK) 1 379 220 (the “Patent”) on the grounds that the Patent lacked an inventive step.

CPR 52.3(6) provides for what would seem to be a uniform and mandatory minimum standard for applications for permission to appeal:

“Permission to appeal may be given only where –

(a) the court considers that the appeal would have a real prospect of success; or

(b) there is some other compelling reason why the appeal should be heard.”

Floyd LJ reviewed the relevant authorities and revised the previous standard required for permission to appeal in patent cases. In the present case, the Patent was concerned with a capsule made of a certain moisture content to be used in a dry powder inhaler for delivery of the powdered active ingredient. Boehringer submitted that Morgan J had wrongly interpreted the evidence of the formulation expert and wrongly dismissed the moisture level as arbitrary.

However, Floyd LJ could see no basis for interfering with the judge’s findings of fact and held that the technical complexity of the background of a case was not a factor which trial judges should take into account in favour of granting permission to appeal. 28. He said that “this is a case where the applicant is seeking, illegitimately, to deconstruct the judge’s overall evaluative judgment on the issue of obviousness.  I do not think either ground has a real prospect of success.  I would refuse permission to appeal”.  

Tadalafil - Canada

On Nov 04, 2016, Federal Court of Appeal in Apotex Inc. v Eli Lilly Canada Inc, 2016 dismissed the appeal relating to double patenting & sufficiency of Canadian Patent No. 2,226,784 (784 Patent). The Court of Appeal had previously considered the issue of double patenting of this patent with a different generic company, Mylan.

The double-patenting issue in the tadalafil (CIALIS) cases concerns two of Lilly’s patents. The earlier patent, Canadian Patent No. 2,181,377 (377 Patent), claims tadalafil and the use of tadalafil in the treatment of various disorders, but not treatment of ED specifically. The later patent, '784 claims the use of tadalafil for the treatment of ED. Mylan and Apotex both alleged that the later patent was invalid for obviousness-type double-patenting over the earlier one.

Apotex also argued that in the court below, Gleason J erred in law when she found that the disclosure of the later patent was sufficient. The FCA held that application of the legal test for sufficiency of disclosure to the facts of the case is a question of mixed fact and law, reviewable on the standard of palpable and overriding error. The FCA refused to revisit Gleason J’s preference for the evidence of Lilly’s experts on this issue and dismissed the appeal.

Mesalamine (Lialda) - USA

On Jan 27, 2017, the U.S. District Court for the Middle District of Florida (Tampa) decided that Shire’s 2020 patent would cover Mylan’s proposed generic tablets. As a result of this decision, the court will issue an injunction that blocks FDA from granting effective approval to Mylan’s ANDA.

Shire is involved in patent infringement litigation with several ANDA filers that are seeking FDA approval to market generic versions of Lialda (mesalamine 1.2 g extended-release tablets) prior to expiration of U.S. Patent No. 6,773,720 (set to expire on June 8, 2020).

In April 2012, Mylan notified Shire that it had filed ANDA with a Para IV certification challenging the ’720 patent. Shire sued Mylan for infringement and trial concluded on Sep 29, 2016. Finally Judge Honeywell decided that Shire proved that Mylan’s generic tablets would infringe the ’720 patent. 

Pemetrexed - USA

On Jan 12, 2017, three-judge panel of CAFC affirmed the decision of district court favoring Lilly on Method of use patent, U.S. 7,772,209 (set to expire on May 24, 2022 with PED). The said patent covers methods of administering folic acid and Vitamin B12 followed by administration of pemetrexed disodium (Alimta).

Several generic manufacturers have submitted ANDAs with Paragraph IV certifications challenging the patents on Alimta. Lilly is still asserting the ’209 patent in infringement litigation. In August 2015, a district court issued a decision in favor of Lilly in its lawsuit against Teva and APP (a subsidiary of Fresenius). Teva and Fresenius filed appeals and court held a hearing on September 9, 2016.

In a thorough opinion, the district court found, inter alia, that a skilled artisan would not have been motivated to: (1) use folic acid pretreatment with pemetrexed; (2) use vitamin B12 pretreatment with pemetrexed; or (3) use the claimed doses and schedules of folic acid and vitamin B12 pretreatments with pemetrexed. The court also found that Eli Lilly had established several secondary considerations in favor of nonobviousness. On appeal, Defendants contend that all of those findings were erroneous. Eli Lilly submits that Defendants’ arguments “amount to nothing more than an effort to reargue the facts.”

CAFC agreed with Eli Lilly and said that Defendants’ arguments fail to raise reversible error with respect to at least the findings that a skilled artisan would not have been motivated to use vitamin B12 pretreatment with pemetrexed, let alone the appropriate doses and schedules of such vitamin B12 pretreatment.