Richard Doble European Patent Attorney MIEEE

Angiotech Pharmaceuticals Inc v Conor Medsystems Inc

House of Lords gives the green light to speculative patent applications provided they pass a “threshold test of disclosing enough to make the invention plausible” Clarification of “obvious to try”

Summary and Introduction

Under existing UK case law, namely Johns-Manville Corporation's Patent [1967] RPC 479 per Diplock LJ, a development is treated as obvious if “the person versed in the art would assess the likelihood of success as sufficient to warrant actual trial.” This concept of “obvious to try” leaves open the question: what qualifies as “success” in the pharmaceutical context:-

i) any therapeutic effect whatsoever,
ii) the therapeutic effect asserted in the patent or
iii) the actual therepeutic effect obtained by a commercial product?

The greater the therapeutic effect required to count as “success,” the less likely that “actual trial” would be “warranted” and the less likely that any given development would be considered obvious. The House of Lords has now held that the therapeutic effect asserted in the patent is the relevant degree of success, “provided that the specification passes the threshold test of disclosing enough to make the invention plausible” - per Hoffmann LJ.

The Patent

The patent at issue, EP0706376, concerned a variety of anti-angiogenic compositions and polymers for treating cancer and included a disclosure of stents coated with anti-angiogenic compositions for the prevention of “recurrent stenosis” (blocking of the lumen of a body passageway such as an artery following angioplasty). Several such “anti-angiogenic” compounds were disclosed including Methotrexate (subsequently shown not to be anti-angiogenic by the CAM assay presented in the
patent and found not to work in a stent) and Heparin (found to be anti-angiogenic by the CAM assay but not to work in a stent). No example or other experimental evidence was presented in the patent to show that any of the disclosed stents did in fact prevent recurrent stenosis but Example 2, headed “Analysis of Various Agents for Anti-angiogenic Activity”, described the results of testing various anti-angiogenics by a CAM assay. It gave prominence to taxol:

“In summary, this study demonstrated that 48 hours after taxol application to the CAM, angiogenesis was inhibited.
The blood vessel inhibition formed an avascular zone which was represented by three transitional phases of
taxol's effect. The central, most affected area of the avascular zone contained disrupted capillaries with extravasated red blood cells; this indicated that intercellular junctions between endothelial cells were absent. The cells of the endoderm and ectoderm maintained their intercellular junctions and therefore these germ layers remained intact; however, they were slightly thickened. As the normal vascular area was approached, the blood vessels retained their junctional complexes and
therefore also remained intact. At the periphery of the taxol-treated zone, further blood vessel growth was inhibited which was evident by the typical redirecting or ‘elbowing’ effect of the blood vessels...Taxol-treated avascular zones also revealed an abundance of cells arrested in mitosis in all three germ layers of the CAM; this was unique to taxol since no previous study has illustrated such an event. By being arrested in mitosis, endothelial cells could not undergo their normal metabolic functions involved in angiogenesis. In comparison, the avascular zone formed by suramin and cortisone acetate
do not produce mitotically arrested cells in the CAM; they only prevented further blood vessel growth into the treated area. Therefore, even though agents are anti-angiogenic, there are many points in which the angiogenesis process may be targeted. We also observed the effects of taxol over the 48 hour duration and noticed that inhibition of angiogenesis occurs as early as 9 hours after application. ... Also, we observed the revascularization process into the avascular zone previously observed. It has been found that the avascular zone formed by heparin and angiostatic steroids became revascularized 60 hours after application. In our study, taxol-treated avascular zones did not revascularize for at least 7 days after application implying a more potent longterm effect.” - as quoted at para [0021] of the H of L judgment.


The patent was extensively amended to focus on taxol and the claims at issue were claim 1 and
(especially) dependent claim 12:
1. A stent for expanding the lumen of a body passageway, comprising a generally tubular structure
coated with a composition comprising an anti-angiogenic factor and a polymeric carrier, the factor
being anti-angiogenic by the CAM assay, and wherein said anti-angiogenic factor is taxol, or an
analogue or derivative thereof.
……
[11. A stent according to any of claims 1 to 5 for treating narrowing of a body passageway.]
12. A stent according to claim 11 for treating or preventing recurrent stenosis.”
Taxol-coated stents had since been shown to be effective and enjoyed considerable commercial
success.
In 1993, at about the same time as the priority date of the patent, a group of Dutch scientists of
high repute in the field published a two-part article entitled Pharmacological Approaches to
the Prevention of Restenosis Following Angioplasty: The Search for the Holy Grail? (Drugs
46(1) 18-52; 46(2) 249-262). This article (referred to in the proceedings as the “Holy Grail”
article) concluded:
“Whether there is a feasible monotherapy, whether we have to focus on a drug combination,
or whether we are searching for the ‘Holy Grail’ remain to be answered.”
The corresponding Dutch patent was upheld by the national court.
Decisions of the Patents Court and Court of Appeal
The Patents Court held that the patent was invalid for obviousness over three citations, which
disclosed the following:
i) Wolff - disclosed a stent coated with an anti-angiogenic drug in biopolymer carrier - but did not
disclose taxol as the anti-angiogenic drug;
ii) Kopia - disclosed techniques for site-specific delivery of various drugs, including delivery of
taxol for treatment of post-angioplasty restenosis. Stents were not disclosed, nor was the concept of
elution of the drug from a polymer.
iii) Katsuda - disclosed in vitro work which showed that taxol prevented mitogenic proliferation
(growth by cell division) of smooth muscle cells.
The general concept of elution of a drug from a polymer on a stent was considered to be part of the
common general knowledge.
The Court of Appeal, following the Patents Court, held that the patent was obvious over Wolff, as
well as Kopia/Katsuda, noting (para [0060]) that “both Wolff and the patent in suit have wide
ranging and overlapping disclosures” and that “Just adding another, self-evident candidate to a list
of things which might be investigated was not enough to make an invention.” A significant
consideration in their reasoning was the premise that no advantage of taxol over other antiangiogenic
drugs had been demonstrated in the patent - so, they reasoned, the aim of the screening
programme would be to find drugs with some usefulness in inhibiting restenosis, a much less
ambitious aim than screening for drugs with the outstanding restenosis-preventing ability which
taxol turned out to possess.
Decision of the House of Lords
The House of Lords implicitly approved the Court of Appeal’s decision in Johns-Manville
Corporation's Patent [1967] RPC 479 which concerned use of a flocculating agent in a process for
making asbestos cement given that it was previously disclosed for use in the mining and paper
industries. That patent was revoked, and Diplock LJ considered that a development should be
treated as obvious if 'the person versed in the art would assess the likelihood of success as
sufficient to warrant actual trial.'
In the present case the House of Lords unanimously rejected the premise of the Court of Appeal
below that no advantage of taxol over other anti-angiogenic drugs had been demonstrated in the
patent and considered that the CAM assay of Example 2 (supra) did in fact make plausible the
teaching in the patent that taxol prevented restenosis. Furthermore in the leading judgment
Hoffmann L J stated:
28. The question was whether that [the ability of taxol to prevent restenosis]
was obvious and not whether it was obvious that taxol
(among many other products) might have this effect. It is hard
to see how the notion that something is worth trying or
might have some effect can be described as an invention in respect of
which anyone would be entitled to a monopoly. It is therefore perhaps
not surprising that the test for obviousness which Pumfrey J
[in the Patents Court, below] devised for such an “invention” was
whether it was obvious to try it without any expectation of success.
This oxymoronic concept has, so far as I know, no precedent in the law of patents (emphasis added).
In paragraph 37 he continued:
“But there is in my opinion no reason as a matter of principle why, if a specification passes the
threshold test of disclosing enough to make the invention plausible, the question of obviousness
should be subject to a different test according to the amount of evidence which the patentee presents
to justify a conclusion that his patent will work” (emphasis added).
Because neither Wolff nor Kopia identified taxol as “particularly suitable” for preventing
restenosis , he held that the patent was non-obvious over this prior art (para 41 of the judgment).
He held that the patent was non-obvious over Katsuda for other reasons.
The judgment of Lord Walker is particularly interesting on the issue of “obvious to try” because he
notes a problem highlighted by a former eminent patents judge, namely that the more pressing a
technical problem, the harder it is to show that a solution is non-obvious and patentable because
researchers will consider even a small likelihood of success “sufficient to warrant actual trial”:
“47. Johns-Manville was decided over forty years ago, and was
concerned with a fairly low-tech process. During the last forty years the
volume of high-tech research has increased enormously, especially in
the fields of pharmaceuticals and biotechnology. The resources
committed to research are enormous, because the potential rewards in
world-wide markets are so great. Competition is fierce. In this climate
“obvious to try” has tended to take on a life of its own as an important
weapon in the armoury of those challenging the validity of a patent.
48. The process has been vividly described in observations made out
of court by Sir Hugh Laddie, Patents – what’s invention got to do with
it? (Chapter 6 in Intellectual Property in the New Millenium, p.93):
‘When patents and patent applications succumb to
invalidity attacks, obviousness is the most common cause.
This inevitably generates friction between the community
of patentees and applicants on the one hand and patent
offices and national courts on the other. A company
which has spent millions of dollars on research and has
produced a valuable new drug will be understandably
irritated when, say, a court declares the patent invalid for
obviousness, thereby opening up the market to competitors
who are free to copy. That irritation is likely to be
particularly acute when the raison d’être of the patent
system is said to be the economic encouragement of
research and development.
The problems can be approached by considering first the
concept of ‘obvious to try’. The classic statement of this
principle is set out in the judgment of the Court of Appeal
in Johns-Manville Corporation's Patent. It was said that a
development should be treated as obvious if ‘the person
versed in the art would assess the likelihood of success as
sufficient to warrant actual trial’. Statements to similar
effect have been made by the EPO.
On its face, this produces an unworkable or irrational test.
If the reward for finding a solution to a problem and
securing a monopoly for that solution is very high, then it
may well be worthwhile for large players to examine all
potential avenues to see if one gives the right result, even
though the prospects of any one of them succeeding are
much less than 50/50. What makes something worth
trying is the outcome of a simple risk to reward
calculation. Yet, if the reward is very large, the avenues
worth trying will be expanded accordingly. So, the more
commercially attractive the solution and the more pressing
the public clamour for it, the harder it will be to avoid an
obviousness attack. In those circumstances a solution
which is quite low down a list of alternatives, all of which
are more or less worth trying, will fail for obviousness; a
consequence which is consistent with the decision in
Brugger v Medic-Aid.’ “
[Note: Brugger v Medic-Aid was a decision of the Patents Court which followed Johns-Manville
and concerned a patent for nebulisers. The relevant passage is as follows:
“First a route may still be an obvious one to try even if it is not possible to be
sure that taking it will produce success, or sufficient success to make it
commercially worthwhile. The latter point is inherent in Johns-Manville
Corporation's Patent…... Secondly, if a particular route is an obvious one to
take or try, it is not rendered any less obvious from a technical point of view merely
because there are a number, and perhaps a large number, of other obvious routes as well.” ]
“Sir Hugh goes on to suggest that as technology advances rapidly, this is
a serious and growing problem.”
……
50. This background helps to explain the question which the judge
asked himself (at the end of para 61 of his judgment), including the
reference to testing a product “without any expectation of success”
(which Lord Hoffmann refers to as an “oxymoronic concept”). The
judge sought to answer the question (para 62) by assessing the
contribution to the art made by the specification, and decided (para 64)
that the only real contribution was a proposal for testing (and no more).
In this way arguments that would normally be regarded as relevant to
insufficiency crept into a challenge on the ground of obviousness.”
At this point it should be interjected that the lower courts’ implied answer to Hugh Laddie’s legal
problem was to judge the effectiveness of the result of the screening: -
if, as presented in the patent, the result is better than might be expected, then the drug or other
means for producing the result is a valid selection invention and is in principle patentable, but not
otherwise. However the lower courts considered that the advantage of the selection must be proved
in the patent and in this context the length of the description (37 pages of description and 34 pages
of drawings) together with the relative paucity of information about restenosis and stents, and the
variety of drugs besides taxol presented in the patent, must have coloured their thinking.
Lord Walker’s judgment continued:
51. Your Lordships all concur, as I do, in Lord Hoffmann’s view that
the judge and the Court of Appeal took too narrow a view of the
specification of the patent in suit, probably because they attached
insufficient weight to the CAM assay. What that assay demonstrated
fell far short of what might have been demonstrated (and was in due
course demonstrated) by clinical trials in treating restenosis after
angioplasty. ….”
He concluded:
“53. The European Patent Office focuses on the need for an invention
to solve a particular technical problem: see for instance AGREVO, Case-
T0939/92, paras 2.4 to 2.4.2. So far as the focus was on stents, there
was a particular technical problem, clearly highlighted in the “Holy
Grail” paper published in 1993. The specification, fairly construed, did
put forward a taxol-eluting stent as the answer to this problem. But that
teaching had to be disentangled from so much extraneous matter that it
nearly got lost.”
Practical Consequences
This is clearly an encouraging decision for patentees, particularly in the pharmaceutical field where
therapeutic effects are often difficult or impossible to predict.
Provided that the specification discloses enough information to make an invention (eg a drug or
medical apparatus) plausible, then if the result promised by the invention is obtained in practice,
and the result is unexpected in the sense that it is better than the outcome expected from screening
that invention and other candidates, then it ought not to be considered “obvious to try.”
Therefore when filing a new patent application, any test results lending plausibility to a potential
“selection invention” should be included even if they do not relate directly to the therapeutic effect.
Any expected therapeutic effect should be asserted in the application as filed even if not fully
backed up by experimental evidence.
Undue length in a patent application should be avoided.

ⓒ Richard Doble September 2008