Tenofovir Disoproxil Fumarate and Emtricitabine (Truvada) - Denmark

Basic Information:
Product: Tenofovir Disoproxil Fumarate and Emtricitabine (Truvada)

Dosage: 300 + 200 mg Tablet; Oral

Innovator: Gilead

Marketing Authorization: EU/1/04/305/001

Generic Filer: Accord Health Care

Patent of Concern: EP0915894

EP’894 Expiry: July 25, 2017 (Patent Expiry) and February 24, 2020 (SPC Expiry)

Points to Ponder: Article 3(a), Basic Patent, Preliminary Injunction & SPC

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Determination of the Danish Maritime and Commercial High Court (October 26, 2017):

Rejected Gilead's motion for preliminary injunction against Accord Healthcare Limited based on Gilead's Danish SPC for the combination of Tenofovir Disoproxil Fumarate and Emtricitabine.

Accord had defended motion for preliminary injunction based on arguing non-infringement and validity.

Invalidity Arguments:

• Claim 27 of the Patent that concerns the potential combination of Tenofovir with another compound which claims an optional combination of Tenofovir with "Other therapeutic ingredients"
• Claims 27 of EP0915894 is :“27. A pharmaceutical composition comprising a compound according to any one of claims 1-25 (N.B.Tenofovir Disoproxil is claimed in claim 25) together with a pharmaceutical carrier and optionally other Therapeutic ingredients.”
• Accord’s Argument:  The SPC's combination of Tenofovir Disoproxil Fumarate and Emtricitabine was not protected by the basic patent.
• The Court Determination:  The SPC had been granted in contrary to Article 3(a) of the SPC Regulation.
• Gilead’s Argument: The skilled person would understand the words "other therapeutic ingredients" in claim 27 as referring to Emtricitabine. Hence, according to Gilead, the combination of Tenofovir Disoproxil Fumarate and Emtricitabine was covered by the basic patent. 
• Accord’s Arguments: The case law from the CJEU dating from after the grant of the SPC makes it clear that a "product" according to the SPC Regulation has to be specified in the claims, either by reference to the compound's name, its chemical structure or by a functional definition, provided that the functional definition necessarily and specifically relates to the compound in question. The words "other therapeutic ingredients" in claim 27 did not specify Emtricitabine, neither by name/chemical structure nor by a functional definition, as the words "other therapeutic ingredients" say nothing about the specific function or nature of such "other therapeutic ingredients".  
• The Court's Determination: The Court agreed with Accord's invalidity arguments stating that Accord, on this basis, had "proved that the certificate-in-suit is invalid". Hence, the motion was rejected.

Infringement Arguments:

• The Court found that, had the SPC been valid, Accord's combination product was covered by the SPC. Accord had argued non-infringement referring to the fact that the SPC was granted for Tenofovir Disoproxil in its Fumarate Salt form in combination with Emtricitabine, whereas Accord's product contained Tenofovir Disoproxil in its Free Base Form. The Court concluded that Gilead's marketing authorisation on which the SPC had been granted, which did not specify the Fumarate Salt form of Tenofovir, covered Tenofovir in all its forms, and, accordingly, so did the SPC.

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Determination of the Eastern High Court in Denmark (March 7, 2018):

Overturned the decision of the Danish Maritime and Commercial High Court and granted the preliminary injunction against Accord. The Eastern High Court is the court of appeal in Denmark. The has Eastern High Court granted a preliminary injunction against Accord Healthcare Limited on the basis of Gilead's Danish SPC for TRUVADA®, overturning the first instance decision of the Maritime and Commercial High Court.

Invalidity Arguments: 

• The Eastern High Court did not accept that Accord had proven that Gilead's SPC was invalid.
• The Eastern High Court’s Determination: Stated, referring to the Protocol on the Interpretation of Article 69 EPC and the Eli Lilly decision that the claims of the basic patent - including in relation to the question of which active ingredients are covered by the claims - should be interpreted in the light of the common general knowledge of the skilled person.
• The Eastern High Court referred to a declaration and oral testimony of Gilead's expert and found that the skilled person at the priority date of the basic patent (July 1996) would have understood "other therapeutic ingredients" as compounds contributing to antiviral activity, including in particular for the treatment of HIV, and therefore that the skilled person would think of a combination of Tenofovir Disoproxil with another NRTI, a NNRTI or a protease inhibitor. The Eastern High Court concluded that the term "other therapeutic ingredients" in claim 27 only concerned a limited number of compounds. 
• Consequently, the Eastern High Court found that it could not be rejected with the sufficient degree of certainty that claim 27 implicitly, but necessarily and specifically also related to Emtricitabine.
• The Eastern High Court also gave weight to the existing doubt as to the interpretation of Article 3(a), in particular in view of the pending referral to the CJEU (C-121/17).

Infringement Arguments: 

• Found that the SPC was infringed even though the title of the SPC mentioned a specific salt of the active ingredient Tenofovir Disoproxil, and Accord's product was not sold as such a salt. 
• The Eastern High Court concluded that Gilead had rendered it probable that the Fumaric Acid Salt and the free base of Tenofovir Disoproxil should be considered the same active ingredient within the meaning of the SPC Regulation. Consequently, Gilead's SPC was infringed by a combination product containing the Free Base of Tenofovir Disoproxil, even though the title of the SPC mentioned Tenofovir Disoproxil as a Fumaric Acid Salt.

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To understand chronology and events of the case, see below mentioned image of The Danish Legal System’s Hierarchy.