Hospira UK Generics (UK) Ltd trading as Mylan v Novartis AG
| Jurisdiction | England & Wales |
| Judge | Lord Justice Floyd,Lord Justice Tomlinson,Lord Justice Patten |
| Judgment Date | 19 December 2013 |
| Neutral Citation | [2013] EWCA Civ 1663 |
| Date | 19 December 2013 |
| Court | Court of Appeal (Civil Division) |
| Docket Number | Case No: A3/2013/1065 |
[2013] EWCA Civ 1663
IN THE COURT OF APPEAL (CIVIL DIVISION)
ON APPEAL FROM THE HIGH COURT OF JUSTICE
CHANCERY DIVISION
Mr Justice Arnold
HC 11 C 04491; HC12 C02558
Royal Courts of Justice
Strand, London, WC2A 2LL
Lord Justice Patten
Lord Justice Tomlinson
and
Lord Justice Floyd
Case No: A3/2013/1065
Justin Turner QC and Miles Copeland (instructed by Bristows LLP) for the Appellant
Michael Tappin QC (instructed by Bird & Bird LLP) and Thomas Mitcheson (instructed by Taylor Wessing LLP) for the Respondents
Hearing date: 11 December 2013
This appeal raises a short point about the entitlement of a patented invention to priority. The patent in suit, European Patent (UK) 296 689, belongs to Novartis AG, and relates to the use of a particular member of the bisphosphonate class of drugs for the treatment of, amongst other things, osteoporosis. The drug in question is called zoledronic acid although it may exist in hydrated forms referred to as zoledronate. I will use the term zoledronate in this judgment to cover all forms. Claim 7 (which is dependent on claim 5) claims the use of a zoledronate medicine for the treatment of osteoporosis where the medicine is adapted for intravenous administration in a unit dosage form which comprises from about 2 up to about 10mg of zoledronate, wherein the period between administrations is about once a year. The claim is in the so-called "Swiss" form, but nothing turns on that.
Claim 7 claims priority from, amongst other documents, United States Patent Application No 267689, referred to in this case as "PD2" because it is the second of two priority documents identified in the patent in suit. The issue, in essence, is whether PD2 discloses the subject matter of claim 7 of the patent.
The issue arose in the context of separate proceedings brought first by Hospira UK Limited and then by Generics (U.K.) Limited (trading as Mylan) for revocation of the patent. Both companies wish to market products falling within claim 7. After a trial, Arnold J decided that the patent in suit and another related patent were wholly invalid. His judgment is to be found at [2013] EWHC 516 (Pat). For present purposes it is enough to record that, as a consequence of the loss of priority, claim 7 was invalid. Novartis appeals only in relation to the judge's finding that claim 7 of the patent in suit was not entitled to priority. It is agreed that claim 7 will be invalid if it is not entitled to priority, because of an intervening publication which would, in consequence, become available for an attack on validity. Equally, it is agreed that if claim 7 is entitled to priority then on the judge's findings claim 7 will be valid. As claim 7 covers Novartis' commercial product ACLASTA, the issue is of some commercial importance to the parties.
The disclosure of PD2
PD2 starts with a statement that the invention relates to bisphosphonates, in particular to the pharmaceutical use of bisphosphonates in the treatment of conditions of abnormally increased bone turnover, such as osteoporosis. After some introduction about bisphosphonates, and discussion of prior art proposals, the specification continues at page 2:
"Surprisingly we have now found that bisphosphonates, in particular recent more potent bisphosphonates, can be used for prolonged inhibition of bone resorption in conditions of abnormally increased bone turnover by intermittent administration, wherein the periods between bisphosphonate administrations are longer than was previously considered appropriate to achieve satisfactory treatment. In particular and contrary to expectation we have found that satisfactory treatment results can be obtained even when the dosing intervals greatly exceed the natural bone remodelling cycle."
PD2 is therefore concerned with dosing interval. For a dosing interval to exceed the natural bone remodelling cycle, it would be longer than three months. The expression "conditions of abnormally increased bone turnover" is explained at page 3 as including postmenopausal osteoporosis, male osteoporosis and drug induced osteoporosis as well as a multitude of other conditions. "Intermittent administration" tells the reader nothing at this stage about the precise mode of administration, or the dosage size. A later passage bridging pages 3 and 4 gives more information as to the dosing interval: "In accordance with the present invention the bisphosphonate dosing interval is at least about 6 months, e.g. once every 180 days, or less frequently, conveniently once a year, or any interval in between, e.g. once every 7, 8, 9, 10, or 11 months. Dosing intervals of greater than once per year may be used, e.g. about once every 18 months or about once every 2 years, or even less frequently, e.g. a frequency of up to about once every 3 years or less often."
The skilled person would have recognised these increased dosing intervals as being of importance. As at June 2000, there were two bisphosphonates which had been approved for the treatment of osteoporosis, etidronate and alendronate. Etidronate was taken orally for 14 days at the beginning of a 90 day dosing cycle, for the remainder of which the patient took daily oral calcium carbonate. Alendronate was taken as 10 mg orally, daily. Alendronate had poor gastro-intestinal tolerance. In order to address this problem, patients were required to take the drug before breakfast with a full glass of water and then remain upright for 30 minutes, preferably being physically active during this time. These recommendations had a negative effect on patient compliance, especially given the prevalence of osteoporosis in older patients for whom such directions were more difficult to follow.
PD2 turns to mode of administration in the following passage on page 7:
"The pharmaceutical compositions may be, for example, compositions for enteral, such as oral, rectal, aerosol inhalation or nasal administration, compositions for parenteral, such as intravenous or subcutaneous administration, or compositions for transdermal administration (e.g. passive or iontophoretic).
Preferably, the pharmaceutical compositions are adapted to oral or parenteral (especially intravenous, intra-arterial or transdermal) administration. Intra-arterial and oral, first and foremost intra-arterial, is considered to be of particular importance. Preferably the bisphosphonate active ingredient is in the form of a parenteral, most preferably an intra-arterial form."
Although there was some evidence that the skilled person might think "intra-arterial" as a mode of administration to be a mistake, there is no doubt that intravenous administration is being put forward as one preferred mode of administration. PD2 explains at page that the particular mode of administration and the dosage may be selected by the physician, taking account of the individual patient's age, size, life style and other characteristics.
As to dosage size, it is explained, also on page 8, that the dosage may depend on various factors, including the effectiveness and duration of action of the active ingredient and, importantly for present purposes, the mode of administration as well as the individual condition: i.e. the ailment that is being treated. PD2 states:
"Normally the dosage is such that a single dose of the bisphosphonate active ingredient from 0.005–20 mg/kg, especially 0.01–10 mg/kg, is administered …"
As these doses are expressed in mg/kg, the amounts given could result in very large unit doses. The document then says that "the dose mentioned above" is typically administered intermittently with a period of at least 6 months between doses, but it may be longer, e.g. once per year, once per 18 months or once every 2 years, or even longer, or any period in between.
PD2 also explains on page 8 that "the actual unit dose", which I have called the dosage size, will depend upon the potency of the bisphosphonate and the dosing interval among other things. Specifically in relation to "more potent, recent bisphosphonates such as zoledronic acid", PD2 says: "a unit dose of from about 1 up to about 10 mg may be used. For example … from about 1 to about 5 mg may be used for dosing once every 6 months; whereas a dose of from about 2 up to about 10 mg may be used for once a year dosing".
I refer to this, simply for convenience, as "the 2–10 mg once a year passage". It occurs immediately after a reference to single dose unit forms for infusion solution doses containing 0.5 to 500 mg of active ingredient, which would be suitable for, but not be limited to, intravenous infusion. The passage also contains a reminder that the unit dose used will depend upon potency of the active ingredient and dosing interval "amongst other things". The "other things" clearly include those discussed earlier, including method of administration and condition.
PD2 contains five Examples. Example 5 is relevant. It describes a Phase 2 12 month clinical trial of zoledronate for the treatment of post-menopausal osteoporosis. Either zoledronate or placebo was administered intravenously. The dosage sizes and intervals in the non-placebo study arms included 4 mg every 12 months (i.e. once). Other regimens included 0.25, 0.5 and 1 mg every 3 months and 2 mg every 6 months. Total annual dosages therefore ranged from 1 to 4 mg per year. Patients were evaluated every three months over the year. All treatment arms demonstrated "a percent change from baseline in BMD significantly (p<0.001) greater than placebo and not dissimilar one from another."
The document states at page 16:
"Suppression of biochemical markers of bone formation and bone resorption confirmed and supported the BMD results, demonstrating...
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