Teva v Leo - A novel test for inventive step?

07 November 2014

In Teva v Leo Birss J. chose not to follow the test in Pozzoli v BDMO when holding the claims of two patents relating to a combination formulation for treating psoriasis invalid as lacking inventive step. The case also raises some interesting questions regarding the impact of patent rights and regulatory issues on the skilled addressee.

Introduction

In Teva v Leo Mr Justice Birss was asked to decide whether two patents (one a divisional of the other) relating to a combined formulation for treatment of psoriasis were valid and infringed. In reaching his judgment that both the patents were invalid for lack of inventive step, Birss J. modified the test set out in Pozzoli v BDMO in response to the unusual way in which the obviousness case was pleaded by Teva.

The judgment therefore gives rise to the following questions of general interest:

  1. How did Birss J. depart from the test in Pozzoli?
  2. Is a judge entitled to assess obviousness without referring to the test in Pozzoli?
  3. Would Birss J.'s decision been different if he had followed the test in Pozzoli?

There are also some further points of interest in the case which do not relate directly to the decision not to use Pozzoli, namely:

  1. What should be assessed in "obvious to try" cases?
  2. What impact do current patent rights and regulatory issues have on (real-life) clinicians in the pharmaceutical industry, and how does this differ from the position of the skilled addressee?
  3. Can something be common general knowledge and yet not referred to in any publicly available document?
  4. What is the level of evidence required to prove "inventive selection"?

We discuss Birss J.'s findings in relation to these aspects of the case below, and comment on them at the end of the article, after first setting out the technical and factual background to the case.

The patents in issue related to a combined formulation for treatment of psoriasis (one is a divisional of the other). In his judgment Birss J. held that the inventive concept of all the claims was "a non-aqueous ointment formulation for dermal use to treat psoriasis comprising calcipotriol [a vitamin D analogue], betamethasone [a corticosteroid] and polyoxypropylene-15-stearyl ether [also known as "Arlamol E"] as a solvent" (paragraph 56).

He was able to do this because Teva had argued that this specific result was obvious, and Birss J. had decided that this formulation would fall within all of the claims of both patents which were asserted as being independently valid. He also held that the skilled addressee was a team comprising a skilled clinician and a skilled formulator.

Teva argued that the claims of Leo's patents were obvious on the following basis:

  • The skilled addressee would be a team comprising at least a skilled clinician and a skilled formulator. The skilled clinician's common general knowledge would lead the skilled person to think of the combination of betamethasone with calcipotriol. The skilled clinician would have liaised with the skilled formulator to produce the ointment.
  • When the skilled formulator was presented with a prior art citation (a US patent, "Turi"), it would have been obvious to use the non-aqueous solvent described in it (Arlamol B - which in Turi is described as appropriate for use with betamethasone ) as a solvent to combine betamethasone with calcipotriol (paragraph 59).

This unusual way of stating the case on obviousness led to Birss J. departing from the traditional way of assessing obviousness under the test set out in Pozzoli v BDMO.

Birss J.'s approach to obviousness - how did he depart from the test in Pozzoli?

In Pozzoli the Court of Appeal set out the following test for assessing obviousness:

"(1) (a) Identify the notional "person skilled in the art"
(b) Identify the relevant common general knowledge of that person;

(2) Identify the inventive concept of the claim in question or if that cannot readily be done, construe it;

(3) Identify what, if any, differences exist between the matter cited as forming part of the "state of the art" and the inventive concept of the claim or the claim as construed;

(4) Viewed without any knowledge of the alleged invention as claimed, do those differences constitute steps which would have been obvious to the person skilled in the art or do they require any degree of invention?"

Birss J. sets out the test at paragraph 50 of the judgment, and the next four headings in the judgment ("Skilled person and the common general knowledge"; "Inventive concept"; "Identify differences"; and "Is the invention obvious?") track the four parts of the test.

Birss J. complies with the first two steps - identify the skilled person and common general knowledge; and identify the inventive concept.

However, when it comes to considering the third step ("Identify differences") Birss J. does not identify the differences between the cited prior art (Turi) and the claimed invention. This is because "Turi on its own does not lead a skilled person to the invention in this case" (paragraph 59). As Birss J. states at paragraphs 57 to 59 of the judgment:

"Most obviousness attacks involve a primary documentary reference. The differences between the primary reference and the invention can be identified (Pozzoli) ...

Some attacks are based on common general knowledge alone, in which case all the elements of the invention are said to derive from common general knowledge alone...

... TEVA's case is unusual in that it starts from common general knowledge and then involves adding information from a document (Turi) which is not part of the common general knowledge and which TEVA do not submit would be found on a literature search. TEVA rely on the principle that any document forming part of the state of the art must be placed before the skilled person. Turi on its own does not lead a skilled person to the invention in this case. Although LEO contend that the argument fails on the facts, they did not object to the argument in principle. I will return to this below. At this stage it means that there is no point in identifying the differences between the invention and a primary reference."

The vast majority of the rest of the judgment (paragraphs 60 to 98) deals (in one guise or another) with the question of whether it would have been obvious for the skilled team to arrive at the invention given the common general knowledge and Turi.

By his own admission, he has departed from Pozzoli at stage 3 - he has not identified "the differences between the invention and a primary reference".

Was Birss J. bound to follow Pozzoli in any event?

There are two reasons why not following Pozzoli may matter. First, it would matter if there was some obligation to follow the test in Pozzoli as a matter of law. Second, it might matter if departing from Pozzoli affects the outcome of the case.

The answer to the first point is that it is clear there is no obligation on a court assessing the obviousness of a claim to use the test in Pozzoli - the statutory wording of s.3 of the Patents Act 1977 does not contain or refer to the test, and the Court of Appeal in Smith & Nephew v Convatec (at paragraph 36) has recently confirm that while "it is often convenient, [it is] by no means essential, to consider an allegation of obviousness using the structured approach explained by this court in Pozzoli v BDMO SA".

The answer to the second question is a little more complicated. In the present case Birss J. didn't use the test because the skilled addressee was a team, and it was his opinion that the common general knowledge of the clinician got him so far, and then Turi was useful only to the formulator to get him to the invention.

It is true that Turi is of no use to the clinician - its disclosure relates to the use of Arlamol E as a solvent, which is only of interest to the formulator. However, it is not clear why, even if Turi was given to the clinician, he would not simply pass it on to the formulator. It is not even clear that it needs to be obvious for him to give it to the formulator in order for the claimed invention as a whole to be obvious.

In Schlumberger Holdings Limited v Electromagnetic Geoservices AS the Court of Appeal stated at paragraph 42 that "what the combined skills (and mind-sets) of real research teams in the art is what matters when one is constructing the notional research team to whom the invention must be obvious if the Patent is to be found invalid on this ground." (emphasis added).

It therefore seems that in most cases the skilled addressee to whom the patent is addressed will have the combined knowledge of the skilled clinician and the skilled formulator together. This will not, however, be the case if (as in Schlumberger) it is inventive for one of the members of the team to go and talk to another. In that case, while the team will be the skilled addressees for the purposes of determining sufficiency, it will not be the skilled addressee for the purposes of determining inventiveness).

It is true, as Birss J. says at paragraph 100 that "an inevitable element of this approach is that it does not matter what the skilled clinicians might have thought of Turi. It is not a document addressed to them". But it is not clear that this matters, and despite the way in which Teva put its case, it is not clear that it was necessary to depart from the test set out in Pozzoli here.

Would Birss J.'s decision been different if he had followed the test in Pozzoli?

Birss J.'s analysis only held the invention to be obvious because of a specific finding relating to the common general knowledge of the clinician - in particular, his (lack of) knowledge regarding pH stability profiles of corticosteroids and vitamin D analogues.

A pH stability profile of a molecule is its ability to exist in a stable form at different pHs. Calcipotriol requires an alkaline pH. In contrast, betamethasone is formulated at an acidic pH to optimise stability.

Birss J. held that the fact of pH stability profiles, and that calcipotriol and betamethasone have different pH stability profiles was common general knowledge to the formulator, but that the clinician did not know of this problem.

This was an important finding, because part of the formulator's common general knowledge was also that there were ways of combining compounds with different pH stability profiles (namely, to use a non-aqueous solvent, which then allowed the disclosure in Turi to be of use).

However, if the clinician had known of pH stability issues, but not how to solve the issue, then on Birss J.'s analysis it is unlikely that he ever would have asked the formulator to try to mix the two together (a little bit of knowledge would have been a dangerous thing).

In contrast, using Pozzoli and the combination of knowledge suggested in Schlumberger, it is clear that, provided that one of them knows it, their knowledge is taken to be combined. Further support for this approach can be found in the statement of the Court of Appeal in Medimmune v Novartis at paragraph 79 that: "There was very little dispute between the parties as to the scope of the common general knowledge of the skilled addressee, that is to say the skilled team to which I have referred."

So on the facts, the same decision would have been reached, but it is clear that this will not always be the case.

What should be assessed in "obvious to try" cases?

At paragraph 53 of his judgment Birss J. discusses Leo's "obvious to try" approach and the concept of "expectation of success". At the end of that paragraph he states that in cases where it is appropriate to ask whether something was obvious to try in determining whether a claim was obvious one must go on to assess the "expectation of success".

In that regard he said: "It is wrong to ask whether something might achieve a particular desired effect. It is correct to ask whether it was obvious that it would achieve that effect".

The judgment discusses (1) "The disclosure of Turi" at paragraphs 74 to 77, (2) "What would the skilled formulator do having read Turi?" at paragraphs 78 to 92 and (3) "Next steps" at paragraphs 93 to 98 (concluding that "both patents are obvious").

However, it is not clear why points (2) or (3) are relevant to the question set - namely "whether it was obvious that [using Arlamol E] would achieve [a stable combination of betamethasone and calcipotriol]".

The question of whether something is obvious is surely a question of whether, before doing anything else it is obvious what will happen. Once the race is run, it is obvious who has won - the question is whether it is obvious who will win before-hand.

Birss J. decided that it would be obvious for the skilled formulator to try Arlamol E, stating that "Based on what the skilled formulator knew about it at the time there was a sufficient prospect of a positive result in the tests with this compound to make it worth testing. It was obvious to do so" (paragraph 92).

Therefore in so answering the question of whether Arlamol E was "obvious to try", Birss J. seems to be answering the very question ("whether something might achieve a particular desired effect") which he has previously stated it is "wrong to ask". In reaching that conclusion he also makes some interesting findings regarding the nature of the skilled team.

What impact do current patent rights and regulatory issues have on (real-life) clinicians in the pharmaceutical industry, and how does this differ from the position of the skilled addressee?

One fact which Leo sought to argue in favour of non-obviousness was that there was no publication by clinicians suggesting that it would be a good thing to have a single combination treatment for psoriasis consisting of calcipotriol combined with betamethasone (regardless of what solvent was used).

Birss J. rejected that argument, stating that there was "some force in TEVA's argument" that "calcipotriol was for all that time a patented product protected by LEO's patent rights" (although he was not sure that Teva's argument was a "complete answer to the point" (all from paragraph 66). The lack of evidence that real-life clinicians had not published or discussed the idea of combining two products was not held to establish that the claimed idea was not obvious.

It should be noted that although there was no evidence of discussions to create a single treatment comprising calcipotriol and betamethasone, Birss J. held (i) that it was common practice of clinicians at the priority date to prescribe calcipotriol and betamethasone to the same patient, and (ii) that the skilled clinician would know that a single combination product was likely to increase patient compliance with the medication, which was a good thing.

This is not the first time that a pre-existing patent right has influenced a judge's finding on what industry players would do. In Glenmark Generics (t/a Mylan) v The Wellcome Foundation Ltd Arnold J. accepted (at paragraph 143) Glenmark's submission that "atovaquone [one of the two drugs combined to form Malarone, the subject-matter of the claims] was itself the subject of patent protection, and therefore no one other than Wellcome [the patentee] could have developed the combination" in order to overcome an argument by Wellcome that commercial success was an indicator that the patented combination was inventive.

A further argument which Leo sought to run was that the skilled formulator, even if given Turi, would not actually try to use Arlamol E as the solvent for the calcipotriol/betamethasone mix because of regulatory considerations. In particular, it sought to argue that "because the skilled formulator would know that the compound has not been used widely in pharmaceutical formulations before, the skilled formulator would be discouraged from using it since that would add potential cost, time and uncertainty to the process." (paragraph 81).

Birss J. rejected these arguments, stating as a matter of principle that while "regulatory process relating to an invention in the pharmaceutical field, are capable of playing a role in the thinking of the notional skilled person as a matter of principle... given that they are commercial rather than directly technical in nature, these factors are unlikely to outweigh technical consideration in any but the strongest cases" (paragraph 82).

In the present case, the skilled formulator, reading Turi, would find out that Arlamol E was listed in the FDA's Inactive Ingredient Guide, which means it has been approved for use by the regulator.

Again, although Birss J. does not refer to Arnold J.'s judgment in Glenmark, similar comments appear there - at paragraph 135 of his judgment Arnold J. states that "the development of anti-malarials was not a field in which the mindset of the skilled person had become conditioned by commercial considerations to exclude certain kinds of technical solutions from consideration".

The position adopted by Birss J. and Arnold J. seems a little odd. Real-life clinicians and formulators are held to not investigate combinations because one of the constitute compounds is patented, but the skilled addressee is not held back by limited regulatory approval or those self-same patents.

This is difficult to square with the statement in Schlumberger that what matters is "the combined skills (and mind-sets) of real research teams in the art... when one is constructing the notional research team to whom the invention must be obvious" (emphasis added).

Surely, if real research teams did not come up with (or even suggest in the literature) the particular invention, especially when there is no assertion that there was something inventive in putting together that particular research team, then that is a good argument that the invention is in fact inventive.

This is particularly the case when one considers that, in contradistinction to the skilled team, the real research team will almost certainly have inventive people within it (the pharmaceutical industry would not exist were it not for innovation).

A similar argument could be made regarding the impact of pre-existing patents. Given that the pharmaceutical industry at large knows that combination patents are likely to be used to provide some extended (although limited) monopoly protection to the original patentee, it is at least arguable that other pharmaceutical companies would be interested in patenting, or at least publishing papers which disclose, such combinations.

Either of these would result in an improvement from the perspective of a non-patentee - in the first case, they obtain the monopoly right, in the second, at least the market for combination products is competitive.

An argument why generic companies do not patent combinations might be that, in fact, the cost of invalidating a patent for a combination product is significantly less than the cost of developing and patenting a combination product. On this basis, generic companies might prefer to allow the original patentee to develop a combination product and patent it, and then apply to invalidate it, ambushing the patentee, and obtaining a first mover advantage against the rest of the industry.

However, this reasoning is less persuasive when applied to making an enabling disclosure - little effort is required to publish an article suggesting the benefit of combining two (or three) pre-existing compounds.

Can something be common general knowledge and yet not referred to in any publicly available document?

The (perhaps rather surprising) answer to this question is that it can be. Birss J. held (at paragraph 101) that "common general knowledge alone would lead the skilled person to think of the combination, would motivate the skilled person to combine the two active agents in a non-aqueous ointment formulation and would motivate the skilled person to draw up a list of solvents to test for use in the ointment" despite the fact that "There was no express reference to the idea of a fixed combination of a corticosteroid and calcipotriol in any of the prior art literature" (paragraph 66).

What is the level of evidence required to prove "inventive selection"?

Birss J. suggests that rather substantial evidence is required. In this case the inventive selection would have been the selection of Arlamol E as the solvent to use in combining betamethasone with calcipotriol. The evidence was that the skilled formulator would "carry out compatibility tests on a number of possible solvents. The number would be about 10 to 20." (paragraph 72).

Leo put to Teva's expert, and he accepted, that propylene glycol (a common non-aqueous solvent) did not work.

Teva had also filed a patent (albeit much later than Leo's patent - Teva's patent was filed on 29 August 2007, compared to LEO's 808 patent, which was filed on 27 January 2000) "addressed to the very same problem of the incompatible pH stability of corticosteroids and vitamin D analogues (such as calcipotriol) in a topical formulation [which] claims the use of certain other compounds as solvents such as triglycerides and polysorbate" (paragraph 89).

However, Leo had not presented evidence about whether these or other solvents which the skilled addressee would have tested would or (preferably for Leo) would not have worked. Therefore, although "such an argument in this case might have been supported by the TEVA patent application... there is not sufficient evidence here to draw such an inference" (paragraph 94).

It would therefore seem that if a patentee wants to run an "inventive selection" argument in situations like these, they would be well placed to have evidence as to what a skilled addressee would normally try, and whether they would work or not.

Comment

It is clear that a judge is not restricted to following the test in Pozzoli in determining whether a claimed invention is obvious.

In the present case, Birss J. set out the test, used part of it, and then decided the case on a different basis (namely by assessing whether it was obvious to try using Arlamol E as the solvent for a combination of calcipotriol and betamethasone). However, while using that test he seemed to apply a different criterion from that which he said was appropriate.

An interesting question is whether the apparent mis-application of these tests is a ground of appeal - as Birss J. is not required to use any particular test, is he (and are judges generally) entitled to use any test to determine the statutory question - was the invention "not obvious"?

As is clear from the counterfactual example set out above, this is not a purely academic question - slightly different fact scenarios can result in different tests producing different results.

The common definition of common general knowledge is that it must be "known to all, not just to some". It is therefore perhaps a slightly surprising outcome of this case that something can be part of the common general knowledge of the skilled team and yet not be written down anywhere.

The case also raises some interesting questions about how the skilled team differs from real-life teams. Both the finding that it was common general knowledge to combine calcipotriol with betamethasone and the finding that it was obvious to try Arlamol E as a solvent were contrary to evidence regarding the actual behaviour of real-life teams. Without these findings, the claims would have been inventive.


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