Gilead Sciences, Inc. v Mylan S.A.S., Generics (U.K.) Ltd T/A Mylan

JurisdictionIreland
CourtCourt of Appeal (Ireland)
JudgeMs. Justice Costello
Judgment Date02 February 2021
Neutral Citation[2021] IECA 22
Date02 February 2021
Docket NumberCourt of Appeal Record Nos. 2019/536 2019/537

[2021] IECA 22

THE COURT OF APPEAL

Costello J.

Haughton J.

Murray J.

Court of Appeal Record Nos. 2019/536

2019/537

BETWEEN
GILEAD SCIENCES, INC.

AND

GILEAD BIOPHARMACEUTICS IRELAND UC
PLAINTIFFS/APPELLANTS
- AND -
MYLAN S.A.S., GENERICS (U.K.) LIMITED T/A MYLAN

AND

MCDERMOTT LABORATORIES LIMITED T/A GERARD LABORATORIES T/A MYLAN DUBLIN
DEFENDANTS/RESPONDENTS
BETWEEN
GILEAD SCIENCES INC

AND

GILEAD BIOPHARMACEUTICS IRELAND UC
PLAINTIFFS/APPELLANTS
- AND -
TEVA B.V. AND NORTON (WATERFORD) LIMITED T/A TEVA PHARMACEUTICALS IRELAND
DEFENDANTS/RESPONDENTS

Supplementary Protection Certificate – Validity – Revocation – Appellants appealing revocation of Supplementary Protection Certificate – Whether the Supplementary Protection Certificate was protected by the basic patent in force

Facts: The respondents in each of the proceedings, Teva B.V. and Norton (Waterford) Ltd t/a Teva Pharmaceuticals Ireland (Teva) and Mylan S.A.S., Generics (UK) Ltd t/a Mylan and McDermott Laboratories Ltd t/a Gerard Laboratories t/a Mylan Dublin (Mylan) respectively, brought a challenge to the validity of a Supplementary Protection Certificate (SPC) held by the appellants, Gilead Sciences, Inc. and Gilead Biopharmaceuticals Ireland UC (Gilead), since 2 September 2009 in respect of TRUVADA®, a combination of Tenofovir Disoproxil (TD) and Emtricitabine (FTC). The validity of the SPC depended upon whether the TD + FTC combination was protected by Patent Number EP (IE) 0915894 (the patent) within the meaning of Art. 3(a) of Regulation (EC) No. 469/2009 (the SPC Regulation). In his judgment, dated 11 October 2019 ([2019] IEHC 683), McDonald J held that it was not so protected and by order dated 8 November 2019 declared the SPC to be invalid, ordering its revocation. Gilead appealed to the Court of Appeal. Gilead’s case was that the TD + FTC combination was protected by the patent and in particular by Claim 27 which provides: “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.” It said TD is one of claims in claims 1-25 and FTC is another therapeutic ingredient which is required to be combined with TD.

Held by Costello J that in order for a product to be protected by the basic patent in force in accordance with the SPC Regulation, it is necessary that each of the active ingredients either be expressly identified or, implicitly, each are necessarily and specifically identifiable. Costello J held that by reason of the fact that FTC was not expressly claimed in the patent and was not necessarily identifiable, the trial judge was correct to hold that the SPC was not protected by the basic patent in force and accordingly, the SPC was properly revoked.

Costello J held that she would refuse the appeal. As Teva and Mylan had succeeded on the appeal, the Court of Appeal was provisionally of the opinion that they were entitled to their costs of the appeal against Gilead, to be adjudicated in default of agreement.

Appeal dismissed. Costs to respondents.

JUDGMENT of Ms. Justice Costello delivered on the 02 day of February 2021
Introduction
1

This appeal arises from a challenge brought by the respondents in each of the above entitled proceedings (“Teva” and “Mylan” respectively) to the validity of a Supplementary Protection Certificate (“SPC”) held by the appellants (“Gilead”) since 2 September 2009 in respect of TRUVADA ®, a combination of Tenofovir Disoproxil (“TD”) and Emtricitabine (“FTC”). The validity of the SPC depends upon whether the TD + FTC combination is protected by Patent Number EP (IE) 0915894 (“the patent”) within the meaning of Art. 3(a) of Regulation (EC) No. 469/2009 (“the SPC Regulation”). In his judgment, dated 11 October 2019 ([2019] IEHC 683), McDonald J. held that it was not so protected and by order dated 8 November 2019 declared the SPC to be invalid, ordering its revocation.

2

Gilead's case is that the TD + FTC combination is protected by the patent and in particular by Claim 27 which provides:-

“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.”

It says TD is one of claims in claims 1-25 and FTC is another therapeutic ingredient which is required to be combined with TD.

Background
3

The trial judge set out the background in considerable detail and this judgment should be read in conjunction with his judgment. In short, the product TRUVADA is a combination therapy for the treatment of HIV infection. The HIV virus causes AIDS. In the early 1980s and 1990s, there were no effective treatments available to many patients suffering from that disease, who went on to succumb to an early death. HIV is a retrovirus which changes the genome of a host cell that it invades. Once inside the host cell, the virus uses its own reverse transcriptase enzyme to produce DNA which is then incorporated into the host cell genome. The viral enzymes are known as DNA polymerases. A class of compounds called nucleoside analogue reverse transcriptase inhibitors (“NRTIs”) were known to inhibit DNA polymerases. Single agent (monotherapy) NRTIs had no long term clinical benefit for HIV patients. While improving the immune function in patients for a period of time, the virus rapidly develops resistance. During the course of 1993, a small clinical trial of combination therapy of two NRTIs found improved immune responses in patients receiving combination therapy, as compared to those in a group of patients receiving monotherapy. By the first half of 1996, combination therapy was accepted as the “gold standard” of care by HIV clinicians globally. Combination therapies might comprise two NRTIs or two NRTIs and one protease inhibitor (“PI”). It was also possible to combine two NRTIs with one non-nucleoside reverse transcriptase inhibitor (“NNRTI”). Since 1996, the preferred treatment for HIV patients has been to use a combination of two NRTIs plus a third agent from a different drug class, such as a PI or NNRTI.

4

FTC is an NRTI which was first synthesised in 1990 and is in a class of NRTIs that selectively block HIV and Hepatitis B virus replication. In vitro investigations had shown that it was a potent inhibitor of the HIV virus. At the priority date of the patent, 26 July 1996, a very small scale stage 1 study involving 18 patients had been conducted. The compound had been described as a “promising candidate for further evaluation as a therapy for infections with HIV and [Hepatitis B].”

5

As I have noted, the other active ingredient in TRUVADA is TD. It is not an NRTI. It is a nucleotide reverse transcriptase inhibitor. While it is chemically distinct from an NRTI, it targets the same stage of the life cycle of the HIV virus. In argument, it was referred to as an NRTI and, while technically this is inconsistent with the findings of the trial judge, for the purposes of this judgment the shorthand of referring to it as an NRTI is adopted. TD is the subject of Claim 25 of the patent and it is also identified as compound 5(f) in Table 2 of Example 16. TD is part of a family of PMP compounds.

6

Nucleotides are “polar” i.e. they include oxygen atoms that are negatively charged in water at neutral pH. This means that they are not readily able to cross cell membranes. If taken orally, a nucleotide would have difficulty crossing the gastrointestinal membranes to enter the circulatory system of the patient. In addition, polar compounds are unable to cross the blood-brain barrier to give access to the brain. In the context of HIV, it is important to ensure that any anti-HIV compound can gain access to the brain in order to eliminate any virus harbouring in that region. The patent seeks to address the bioavailability problem thus arising from the fact that the nucleotide drug is polar and therefore cannot easily cross cell walls.

The patent
7

The patent is entitled “Nucleotide Analogs”. Paragraph 0001 describes the invention in terms that it “relates to intermediates for phosphonomethoxy nucleotide analogs, in particular intermediates suitable for use in the efficient oral delivery of such analogs.” The inventive concept of the patent is to improve the bioavailability of the compounds by providing “intermediates” in the form of prodrugs which would be suitable for oral deliveries and which would enable the intermediate to pass through the cell wall.

8

Paragraph 0044 describes a wide range of viral infections to which the compounds of the invention may be relevant. HIV is included in the list but it is only one of many, very serious viral infections affecting not only humans but also animals, and infections caused by DNA viruses and RNA viruses and other retroviruses thus identified. Prof. Stanley Roberts, a medicinal chemist, who gave evidence in the High Court on behalf of Teva, said that it would be clear to the medicinal chemist that the patent was claiming wide utility in relation to a large range of common viruses in humans, as well as some viruses in animals. Similar evidence was given by Dr. David Hawkins, on behalf of Teva, and by Dr. Graeme Moyle, on behalf of Mylan. Dr. Moyle emphasised that the viruses listed in para. 0044 were very common and causative of many clinically important diseases in both humans and animals as at the priority date. Dr. Hawkins emphasised that Hepatitis B was “a massive problem with maybe two billion people around the world infected and several hundred million with active infection and in fact 500,000 people a year dying of Hepatitis B”.

9

Prof. William Powderly, who gave evidence on behalf of Gilead, emphasised that the focus of the patent was on HIV. He did not dispute Dr. Hawkin's evidence but said that the scale and nature of HIV as of July 1996 was the greatest known threat in infectious...

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