The Cialis Dosing Appeal - Actavis Group PTC EHF and Others v ICOS Corporation and another
In The Cialis Litigation - Actavis Group PTC EHF and Others v Icos Corp and Another 4 Oct 2016, I discussed Mr Justice Birss's judgment in Actavis and others v Eli Lilly and Co [2016] EWHC 1955 (Pat) (10 Aug 2016) in which he dismissed a claim for the revocation of European patent (UK) No 1,173,181 "Compositions comprising phosphodiesterase inhibitors for the treatment of sexual dysfunction" and held that the patent had been infringed, His judgment was reversed by the Court of Appeal (Lord Justices Lewison, Kitchin and Floyd) in Actavis Group PTC EHF and another v Teva UK Ltd and others [2017] EWCA Civ 1671, 159 BMLR 108, (2018) 159 BMLR 108, [2018] RPC 7 (1 Nov 2017) on the ground that the claims relied upon had been obvious. The patentee and its exclusive licensee in the UK appealed to the Supreme Court against the judgment of the Court of Appeal.
The Patent
The patent in suit relates to the use of tadalafil (better known as Cialis), to treat erectile dysfunction or "ED". The drug and its properties were already known as was a rival product called sildenafil or Viagra. Also known from European patent (UK) No 0 839 040 Use of cgmp-phosphodiesterase inhibitors to treat impotence was the idea of using tadalafil and another compound for treating ED. It taught that doses of those compounds will range from 0,5 to 800 milligrams a day for the average patient. That patent is referred to as "Daugan" in the litigation after its inventor, Alain Claude-Marie Daugan. However, Daugan did not purport to set out an appropriate dosage regime as an oral treatment of ED. The patented invention, on the other hand, discloses a pharmaceutical dosage form for human pharmaceutical use of about 1 to about 5mg of tadalafil in a unit dosage form suitable for oral administration for the treatment of sexual dysfunction, including ED up to a maximum total dose of 5mg per day.
Commercial Importance
That dosage regime was potentially of considerable value to the manufacturers of Cialis for it meant that Cialis could safely be taken every day and not when it was needed as was the case with Viagra,
The Issues
Lord Hodge, who delivered the judgment of the Supreme Court on behalf of all the justices, said at paragraph [2] of his judgment that the principal issues in the appeal were the application of the obviousness test to a dosage patent and whether an appeal court was entitled to reverse the decision of the trial judge in the circumstances of the case.
The Judgment
The Supreme Court dismissed the appeal and found that the Court of Appeal had been right to reverse the judgment of Mr Justice Birss. Lord Hodge summarized the Court's judgment in a video and press summary. Videos of counsels' arguments on the morning and afternoon of 19 Nov 2018 and the morning of 20 Nov 2018 can be accessed through the Supreme Court's website.
The Judgment at First Instance
Lord Hodge described Mr Justice Birss's reasoning in paragraph [35] of his judgment:
"In his careful assessment of their evidence Birss J held, at paras 287 et seq, that it would have been “entirely obvious” for a skilled team given Daugan to set out to take tadalafil forward into a routine pre-clinical and clinical trial programme as an oral treatment for ED at the priority date. The Phase I studies would produce results which would lead the skilled team to design and undertake the Phase IIa “go no-go” study of a single 50mg dose of tadalafil in a relatively small group of patients. They would embark on that study with a reasonable expectation that the drug would be safe, tolerable and effective at that dose. Turning to the Phase IIb studies, Birss J concluded that the first dose ranging study would be of on demand dosing using 25, 50 and 100mg of the drug. He did not accept Mr Muirhead’s suggestion that a 5mg dose would be included in this first study. The skilled team’s expectations would be that they would hope that the study would show a dose response relationship. But the results would not be what the team expected because they would show no difference in efficacy between the three doses, demonstrating an apparent therapeutic plateau."
In the next four paragraphs, his lordship traced the steps by which the trial judge arrived at his conclusion that claim 7 of the patent in suit involved an inventive step.
The Court of Appeal
The Court of Appeal set aside Mr Justice Birss's judgment for the following reason which appears at para [152] of Lord Justice Kitchin's judgment:
“The judge has lost sight of the fact that, on his own findings, the claimed invention lies at the end of the familiar path through the routine pre-clinical and clinical trials’ process. The skilled but non-inventive team would embark on that process with a reasonable expectation of success and in the course of it they would carry out Phase IIb dose ranging studies with the aim of finding out, among other things, the dose response relationship. It is very likely that in so doing they would test a dose of 5mg tadalafil per day and, if they did so, they would find that it is safe and efficacious. At that point they would have arrived at the claimed invention. In my judgment claims 7 and 10 are therefore invalid.”
The patent in suit relates to the use of tadalafil (better known as Cialis), to treat erectile dysfunction or "ED". The drug and its properties were already known as was a rival product called sildenafil or Viagra. Also known from European patent (UK) No 0 839 040 Use of cgmp-phosphodiesterase inhibitors to treat impotence was the idea of using tadalafil and another compound for treating ED. It taught that doses of those compounds will range from 0,5 to 800 milligrams a day for the average patient. That patent is referred to as "Daugan" in the litigation after its inventor, Alain Claude-Marie Daugan. However, Daugan did not purport to set out an appropriate dosage regime as an oral treatment of ED. The patented invention, on the other hand, discloses a pharmaceutical dosage form for human pharmaceutical use of about 1 to about 5mg of tadalafil in a unit dosage form suitable for oral administration for the treatment of sexual dysfunction, including ED up to a maximum total dose of 5mg per day.
Commercial Importance
That dosage regime was potentially of considerable value to the manufacturers of Cialis for it meant that Cialis could safely be taken every day and not when it was needed as was the case with Viagra,
The Issues
Lord Hodge, who delivered the judgment of the Supreme Court on behalf of all the justices, said at paragraph [2] of his judgment that the principal issues in the appeal were the application of the obviousness test to a dosage patent and whether an appeal court was entitled to reverse the decision of the trial judge in the circumstances of the case.
The Judgment
The Supreme Court dismissed the appeal and found that the Court of Appeal had been right to reverse the judgment of Mr Justice Birss. Lord Hodge summarized the Court's judgment in a video and press summary. Videos of counsels' arguments on the morning and afternoon of 19 Nov 2018 and the morning of 20 Nov 2018 can be accessed through the Supreme Court's website.
The Judgment at First Instance
Lord Hodge described Mr Justice Birss's reasoning in paragraph [35] of his judgment:
"In his careful assessment of their evidence Birss J held, at paras 287 et seq, that it would have been “entirely obvious” for a skilled team given Daugan to set out to take tadalafil forward into a routine pre-clinical and clinical trial programme as an oral treatment for ED at the priority date. The Phase I studies would produce results which would lead the skilled team to design and undertake the Phase IIa “go no-go” study of a single 50mg dose of tadalafil in a relatively small group of patients. They would embark on that study with a reasonable expectation that the drug would be safe, tolerable and effective at that dose. Turning to the Phase IIb studies, Birss J concluded that the first dose ranging study would be of on demand dosing using 25, 50 and 100mg of the drug. He did not accept Mr Muirhead’s suggestion that a 5mg dose would be included in this first study. The skilled team’s expectations would be that they would hope that the study would show a dose response relationship. But the results would not be what the team expected because they would show no difference in efficacy between the three doses, demonstrating an apparent therapeutic plateau."
In the next four paragraphs, his lordship traced the steps by which the trial judge arrived at his conclusion that claim 7 of the patent in suit involved an inventive step.
The Court of Appeal
The Court of Appeal set aside Mr Justice Birss's judgment for the following reason which appears at para [152] of Lord Justice Kitchin's judgment:
“The judge has lost sight of the fact that, on his own findings, the claimed invention lies at the end of the familiar path through the routine pre-clinical and clinical trials’ process. The skilled but non-inventive team would embark on that process with a reasonable expectation of success and in the course of it they would carry out Phase IIb dose ranging studies with the aim of finding out, among other things, the dose response relationship. It is very likely that in so doing they would test a dose of 5mg tadalafil per day and, if they did so, they would find that it is safe and efficacious. At that point they would have arrived at the claimed invention. In my judgment claims 7 and 10 are therefore invalid.”
Obviousness
Lord Hodge started from first principles at paragraph [53] referring to the Statute of Monopolies 1623 and citing the judgment of Lord Mansfield in Liardet and another v Johnson and another [1780] EngR 75; (1780) 1 Y & CCC 527; 62 E.R 1000 (5 July 1780):
“The condition of giving encouragement is this: that you must specify upon record your invention in such a way as shall teach an artist, when your term is out, to make it - and to make it as well by your directions: for then at the end of the term, the public shall have benefit of it. The inventor has the benefit during the term, and the public have the benefit after …”
He considered the conditions for patentability, and, in particular, the need for an inventive step. He listed the Windsurfing/Pozzoli questions and referred to the European Patent Office's Problem and Solution Approach in its examination guidelines (see the EPO’s Guidelines for Examination in the EPO (November 2017) (Part G - Chapter VII) para 5). At paragraph [62] of his judgment, Lord Hodge stressed:
"While both approaches focus on the inventive concept put forward in the claims, neither approach should be applied in a mechanistic way. Both are glosses on the text of section 3 of the 1977 Act and article 56 of the EPC and neither require a literalist approach to the wording of the claim in identifying the inventive concept."
That was consistent with the decision of Mr Justice Kitchin as he then was in Generics (UK) Ltd and others v H Lundbeck A/S [2007] RPC 32, [2007] RPC 729, [2007] EWHC 1040 (Pat) which had been endorsed by the House of Lords in Conor Medsystems Inc v Angiotech Pharmaceuticals Inc [2008] RPC 28, [2008] UKHL 49:
“The question of obviousness must be considered on the facts of each case. The court must consider the weight to be attached to any particular factor in the light of all the relevant circumstances. These may include such matters as the motive to find a solution to the problem the patent addresses, the number and extent of the possible avenues of research, the effort involved in pursuing them and the expectation of success.”
Lord Hodge started from first principles at paragraph [53] referring to the Statute of Monopolies 1623 and citing the judgment of Lord Mansfield in Liardet and another v Johnson and another [1780] EngR 75; (1780) 1 Y & CCC 527; 62 E.R 1000 (5 July 1780):
“The condition of giving encouragement is this: that you must specify upon record your invention in such a way as shall teach an artist, when your term is out, to make it - and to make it as well by your directions: for then at the end of the term, the public shall have benefit of it. The inventor has the benefit during the term, and the public have the benefit after …”
He considered the conditions for patentability, and, in particular, the need for an inventive step. He listed the Windsurfing/Pozzoli questions and referred to the European Patent Office's Problem and Solution Approach in its examination guidelines (see the EPO’s Guidelines for Examination in the EPO (November 2017) (Part G - Chapter VII) para 5). At paragraph [62] of his judgment, Lord Hodge stressed:
"While both approaches focus on the inventive concept put forward in the claims, neither approach should be applied in a mechanistic way. Both are glosses on the text of section 3 of the 1977 Act and article 56 of the EPC and neither require a literalist approach to the wording of the claim in identifying the inventive concept."
That was consistent with the decision of Mr Justice Kitchin as he then was in Generics (UK) Ltd and others v H Lundbeck A/S [2007] RPC 32, [2007] RPC 729, [2007] EWHC 1040 (Pat) which had been endorsed by the House of Lords in Conor Medsystems Inc v Angiotech Pharmaceuticals Inc [2008] RPC 28, [2008] UKHL 49:
“The question of obviousness must be considered on the facts of each case. The court must consider the weight to be attached to any particular factor in the light of all the relevant circumstances. These may include such matters as the motive to find a solution to the problem the patent addresses, the number and extent of the possible avenues of research, the effort involved in pursuing them and the expectation of success.”
The Appropriate Test
Between paragraphs [64] and [74] Lord Hodge listed 10 factors that he considered relevant to this case. The last of those factors was the nature of the invention. His lordship noted that the Court was concerned with a dosage patent with a Swiss-style claim and a post diplomatic conference claim.
Dosage Patents
Dosage patents had been allowed in England and by the European Patent Office. However, Lord Justice Jacob stressed in Actavis UK Ltd v Merck & Co Inc, [2009] 1 WLR 1186, [2009] 1 All ER 196, [2008] EWCA Civ 444, [2009] Bus LR 573, [2008] RPC 26 ,that such patents would be rare:
“So holding is far from saying that in general just specifying a new dosage regime in a Swiss-form claim can give rise to a valid patent. On the contrary nearly always such dosage regimes will be obvious - it is standard practice to investigate appropriate dosage regimes. Only in an unusual case such as the present (where, see below, treatment for the condition with the substance had ceased to be worth investigating with any dosage regime) could specifying a dosage regime as part of the therapeutic use confer validity on an otherwise invalid claim.”
Mr Justice Birss's Reasoning
Lord Hodge respected the trial judge's finding that there was no defined standard of minimal efficacy in relation to ED and that this would require the skilled team to make a value judgment. However, he also noted that Mr Justice Birss had also found that it was common general knowledge that regulators were often interested in and could require evidence of the minimum effective dose and that the skilled team would be familiar with multiple dose-ranging studies as necessary as a generality. In Lord Hodge's view, the inventiveness of the dosage regime fell to be assessed in that context. It can be inferred that the Supreme Court did not consider the need to make a value judgment to be the sort of "unusual case" that Lord Justice Jacob had in mind in the Actavis case.
Lord Hodge respected the trial judge's finding that there was no defined standard of minimal efficacy in relation to ED and that this would require the skilled team to make a value judgment. However, he also noted that Mr Justice Birss had also found that it was common general knowledge that regulators were often interested in and could require evidence of the minimum effective dose and that the skilled team would be familiar with multiple dose-ranging studies as necessary as a generality. In Lord Hodge's view, the inventiveness of the dosage regime fell to be assessed in that context. It can be inferred that the Supreme Court did not consider the need to make a value judgment to be the sort of "unusual case" that Lord Justice Jacob had in mind in the Actavis case.
Whether the Court of Appeal was entitled to reverse Mr Justice Birss's Judgment
Lord Hodge considered the circumstances in which an appellate court could reverse a judgment of a lower tribunal. His lordship reminded himself of Lord Hoffmann's observation in Biogen Inc v Medeva Plc (1997) 38 BMLR 149, [1997] RPC 1, [1996] UKHL 18 that it would be wrong to interfere with the judge’s assessment if no question of principle is involved. In Lord Hodge's view a "question of principle" went further than an error of law. It could include a failure to apply a legal standard to an assessment of facts. There was evidence before Mr Justice Birss that a skilled team would have ascertained the optimum dosing regime in performing the Daugan patent. The judge had been wrong not to take account of it.
Conclusion
Conclusion
The Supreme Court's conclusion is summarized in paragraph [105] of Lord Hodge's judgment:
"The balance or symmetry in patent law and the pre-established or at least readily foreseeable target of the skilled team’s tests hold the key to the resolution of this dispute. The Daugan patent is ex hypothesi valid and it is not in dispute that it discloses an invention - that is the use of tadalafil in the treatment of ED - in a manner which enables the skilled person to perform it as section 14 (3) of the 1977 Act requires. The task which the notional skilled team would undertake was that of implementing Daugan. The target of the skilled team would be to ascertain the appropriate dose, which would usually be the lowest effective dose. The skilled team would know of that target from the outset of its research. The pre-clinical and clinical tests involved familiar and routine procedures and normally progressed to the discovery of the dose-response relationship in Phase IIb. In this case the trial judge’s findings of what would have been the sequence of the tests, which did not depend upon hindsight, included the finding, which the evidence clearly justified, that the team, having found a therapeutic plateau, would be very likely to test lower doses and so come upon the dosage regime which is the subject matter of the patent. For the reasons which I have given above, I am satisfied that the Court of Appeal was entitled to interfere with the trial judge’s assessment of obviousness and to hold that the 181 patent was invalid for lacking an inventive step."
"The balance or symmetry in patent law and the pre-established or at least readily foreseeable target of the skilled team’s tests hold the key to the resolution of this dispute. The Daugan patent is ex hypothesi valid and it is not in dispute that it discloses an invention - that is the use of tadalafil in the treatment of ED - in a manner which enables the skilled person to perform it as section 14 (3) of the 1977 Act requires. The task which the notional skilled team would undertake was that of implementing Daugan. The target of the skilled team would be to ascertain the appropriate dose, which would usually be the lowest effective dose. The skilled team would know of that target from the outset of its research. The pre-clinical and clinical tests involved familiar and routine procedures and normally progressed to the discovery of the dose-response relationship in Phase IIb. In this case the trial judge’s findings of what would have been the sequence of the tests, which did not depend upon hindsight, included the finding, which the evidence clearly justified, that the team, having found a therapeutic plateau, would be very likely to test lower doses and so come upon the dosage regime which is the subject matter of the patent. For the reasons which I have given above, I am satisfied that the Court of Appeal was entitled to interfere with the trial judge’s assessment of obviousness and to hold that the 181 patent was invalid for lacking an inventive step."
Contact
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Anyone wishing to discuss this case or patents, in general, should call me on 020 7404 5252 during office hours or send me a message through my contact form,
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