Sustained release fluvastatin formulations – The UK Court of Appeal opinion in Activis UK Limited v Novartis AG [2010] EWCA Civ 82

Posted on February 19, 2010 by Warren Woessner

Post from Paul Cole

Sometimes a decision as to obviousness hinges on a single short point. In Graham v John Deere, the tipping point testimony was during cross-examination of the witness for the patentee, when he said that the allegedly inventive feature made no significant difference to the operation of the device. Once that evidence had been given, the outcome was inevitable, and references to Thomas Jefferson, though decorative, were mere dicta.

The controversy concerning the fluvastatin sustained release patent EP-B-0948320 (UK) falls into the same category. The patent was based on the premise that fluvastatin was so water-soluble that it was difficult to devise a sustained release formulation. Claim 1 as amended read:

A sustained release pharmaceutical composition comprising a water soluble salt of fluvastatin as active ingredient and being selected from the group consisting of matrix formulations, diffusion-controlled membrane coated formulations and combinations thereof, wherein the sustained release formulation releases the active ingredient over more than 3 hours.

The tipping point fact was that fluvastatin was not of such extreme water-solubility as to give rise to the difficulties alleged. After that had been established, the whole basis for patentability collapsed, as explained concisely by Jacob L.J. at the conclusion of his opinion, which also contains an implied warning that although it may be appropriate to rely on an earlier decision for a rule of law, the facts on which that earlier decision was reached are of little relevance:

Once the obstacle put forward in the Patent against being able to make a sustained formulation was shown to be illusory, then a sustained release formulation is obvious. You might get better efficacy or fewer side effects, but you would certainly get better compliance. In Pozzoli terms the only difference between the prior art and the claim is the idea of making a sustained release formulation. For that there was a technical motivation and no difficulty, real or apparent.

The PSA [problem-solution analysis] gives the same answer. What is the objective problem? Why that which the patentee himself stated – to produce a sustained release form of fluvastatin. Was the solution obvious? Yes, any of the standard methods for such formulations would clearly work: there is no reason why they would not.

There is no need and it would be wrong to re-formulate the problem as suggested by Mr. Meade. This is not a case where some prior art unknown to the patentee has turned up. Nor is it right to reformulate the problem as one of looking for better medical effects when that was not the problem as seen by the patentee or to reformulate the solution as having found such effects when the patentee has not promised any.

In the latter respect this case is quite unlike the case, relied upon by Mr. Meade, about a sustained release form of oxycodone recently considered by this court, Napp v Ratiopharm [2009] EWCA Civ 252, [2009] RPC 539. Oxycodone was, until the patent, known as a minor weak opiod generally administered, to the extent that it was administered at all, as a co-drug. The slow-release form transformed it, as the patent said, into a serious alternative to morphine – something that was wholly unexpected. Of course the invention was non-obvious.

The upshot is that I would uphold the decision of the Judge. Unlike him, however, I do not think the case was finely balanced. Once the basis of the Patent was proved illusory there was nothing left to save it.

Jacob L.J.’s opinion contains a lengthy discussion of the respective approaches to inventive step of the UK courts under Windsurfing/Pozzoli and of the EPO approach using PSA which may be valuable to students and has been praised as “a tutorial in the law of obviousness”. Readers may recall John Mortimer’s fictional barrister Rumpole, who knew little law, but was an expert on bloodstains and used his instinct for tipping point facts with devastating effect in the cases for which he was responsible. No magic touchstone is to be found either in the USA under Graham/KSR or in the UK under Windsurfing/Pozzoli because in both jurisdictions after certain mandatory preliminary enquiries the issue has to be decided on a case by case basis according to the evidence and without the distortion introduced by preconceptions in the mind of the decision-maker. The legal background is only a guide as to the appropriate enquiries to be made and what matters is the evidence as to the tipping point facts, of which in the present case there was only one.

Posted in Non-U.S. Practice | Tagged , , , | Leave a comment

END OF AN ERA – “SWISS-FORM” CLAIMS ARE OUT

Posted on February 19, 2010 by Warren Woessner

The Enlarged Board of Appeal of the EPO issued a decision on February 19th (G02/08), that Swiss-form claims will no longer be permitted as a way to claim a “second medical use” of a bioactive agent – “The use of compound x to prepare a medicament to treat condition y”. Rather, the form of “first medical use” claims is to be used: “[Known compound x] for use in [treating condition y].” (First medical use claims are simply: “Use of compound x for treatment of condition y” – in older applications, first medical use claims often appear simply as “Use of compound x in medical therapy,” but this form is often deemed objectionably vague these days.)

The decision is not retroactive, and will apply only to applications having a priority date three months after the Decision is published in the Official Journal of the EPO (which has  not yet occurred). Thanks to Marks & Clerk UK for getting the word out so quickly.

Posted in Non-U.S. Practice | Tagged , , , | Leave a comment

Claims to “New Uses of Old Compounds” – The Noose Tightens

Posted on February 19, 2010 by Warren Woessner

In Perricone v. Medicis, 432 F.3d 1368 (Fed. Cir. 2005), the court reversed the Board, and found that a claim to treating sunburn with certain vitamin esters was patentable in view of art disclosing the same compounds to benefit normal skin. The Board had found the claim invalid as inherently anticipated by the prior art use, but the court found no disclosure in the prior art of applying the compounds to sunburned skin.

In Ex parte Matsubara, Appeal 2009-006581 (Feb. 10, 2010), the Board affirmed the Examiner’s rejection of a claim to a method for improving bone metabolism by (a) selecting a human or animal having a tendency toward a decrease in bone density (e.g., afflicted with osteoporosis), and (b) therapeutically administering to said human or animal certain types of fermented soy milk or “FSM.”  The Examiner rejected the claim as inherently anticipated by a publication that disclosed studying the lipid metabolism in aged, ovariectomized rats after giving them FSM, in view of a publication that established that such rats were an art-recognized model of osteoporosis. Applicants argued that the prior art showed no effect of FSM on osteoporosis and no “selection step” of choosing the rats to evaluate, since the prior art was not concerned with studying osteoporosis.

After quoting sections of Perricone discussing inherency, that the Fed. Cir. panel found inapplicable to the decision that it reached, the Board affirmed the rejection, stating that “the claimed method ‘is inherent and in the public domain if it is the “natural result flowing from” the explicit disclosure of the prior art’…regardless of whether the inherent result is recognized.”  Although I have argued that the use of an old compound for a “different purpose” than disclosed in the art should be sufficient to distinguish the prior art use if a “new use for an old compound” is being claimed, Perricone may deserve a closer reading.

It may well be that the Fed. Cir. reversed in Perricone because no manipulative step of applying the esters to sunburned skin was disclosed in the prior art, not simply because the claimed purpose was not in the prior art. The panel did begin by agreeing: “If [the prior art] discloses the very same methods, then the particular benefits must naturally flow from those methods even if not recognized as benefits at the time of [the art’s] disclosure. Thus [the art] anticipates if its disclosure of ‘topical application’ satisfies the application step in Dr. Perricone’s various asserted claims.” The panel went on to find that the art did not disclose the application step of applying the esters to sunburned skin.

So, given that new uses of old compounds remain statutory subject matter and can be extremely valuable, how do we claim them? I think it is important that the prior art rats given FSM and the rats treated by Matsubara were both models for osteoporosis. At least some Examiners give weight to the value of “selection” or recognition that a specific subpopulation can be helped by administration of an “old drug.” For example, consider a claim to “a method of treating a human male afflicted with prostate cancer comprising administering an effective anti-cancer amount of Lipitor to said human male.” Hopefully, the prior art does contain a publication on the treatment of prostate cancer with a chemotherapeutic agent, e.g., docetaxel, that also incidentally discloses that some of the patients were given Lipitor to lower cholesterol. Then you are left hoping that the inventor’s dosing regimen is different than the standard dosing regiment used to lower cholesterol. The noose tightens.

Posted in Patenting Methods/Processes | Tagged , , , , , , | Leave a comment

Views of the EPO Enlarged Appeal Board in Treatment by surgery/MEDI-PHYSICS G 0001/07

Posted on February 18, 2010 by Warren Woessner

Under what circumstances is injection a prohibited surgical method? Views of the EPO Enlarged Appeal Board in Treatment by surgery/MEDI-PHYSICS G 0001/07 .  Opinion

From Paul Cole

The present proceedings resulted from a referral in decision T 0992/03 relating to EP-A-1066537. That specification was concerned with magnetic resonance methods for imaging the pulmonary and/or cardiac vasculature and evaluating blood flow using dissolved polarised 129Xe. Representative claims presented to the Appeal Board are set out below

1.  A method for MRI imaging the pulmonary and/or cardiac vasculature using dissolved-phase polarized 129Xe, comprising the steps of:

            positioning a patient in an MRI apparatus having a magnetic field associated therewith;

            delivering polarized 129Xe gas to a predetermined region of the patient’s body, the polarized gas having a dissolved imaging phase associated therewith;

            exciting a predetermined region of the patient’s body, having a portion of the dissolved phase polarized gas therein with at least one large flip angle RF excitation pulse; and

            acquiring at least one MR image associated with the dissolved phase polarized gas after said exciting step.

6.  A method according to any of Claims 1 to 5, wherein

          said delivering step includes having the patient inhale the polarized 129Xe gas into the lungs, the 129Xe having a gas phase resonance which is higher than the dissolved-phase resonance, and wherein at least a portion of the 129Xe gas enters into the pulmonary vasculature in a dissolved-phase, and wherein at least a portion of the dissolved-phase 129Xe then enters the blood stream with an associated perfusion rate.

22. Use of 129Xe for the preparation of a hyperpolarized imaging agent for use in methods of treatment or diagnosis involving performance of the method as described in any one of claims 1 to 21.

The Appeal Board held that the claimed subject matter did not fall within the diagnostic method exclusion because the claimed steps were confined to the examination phase and did not include steps considered constitutive for making a diagnosis. However the claimed method covered administration of polarised xenon into the heart by injection, and the method was intended to be used inter alia for providing real-time feedback during surgery. Existing case law of the Appeal Boards had held that introduction of a catheter into the pericardial pace was an excluded method of surgical treatment (T 0035/99; see also T 0182/90 as to methods of injection), but that applying radiation to the body for the purpose of cosmetic removal of hair was not excluded (T 0383/03). Issues arising in the appeal to the Enlarged Board included whether it was possible to exclude the administration step (“pre-delivered contrast agent”) or whether the claim would be allowable if the administration step were defined at a higher level of abstraction (“administering a contrast agent”).

In particular, the Appeal Board considered that clarification of the term “treatment by surgery” was required and referred to the Enlarged Board the following questions:

1. Is a claimed imaging method for a diagnostic purpose (examination phase within the meaning given in G 1/04), which comprises or encompasses a step consisting in a physical intervention practised on the human or animal body (in the present case, an injection of a contrast agent into the heart), to be excluded from patent protection as a “method for treatment of the human or animal body by surgery” pursuant to Article 52(4) EPC if such step does not per se aim at maintaining life and health?

2. If the answer to question 1 is in the affirmative, could the exclusion from patent protection be avoided by amending the wording of the claim so as to omit the step at issue, or disclaim it, or let the claim encompass it without being limited to it?

3. Is a claimed imaging method for a diagnostic purpose (examination phase within the meaning given in G 1/04) to be considered as being a constitutive step of a “treatment of the human or animal body by surgery” pursuant to Article 52(4) EPC if the data obtained by the method immediately allow a surgeon to decide on the course of action to be taken during a surgical intervention?

The above questions were answered in an 80 page opinion of the Enlarged Board handed down on 15 February 2010.

The Enlarged Board reaffirmed the position in G 0001/04 that any therapeutic or surgical feature in a method claim causes that claim to fall under the prohibition, and “surgery” is not to be interpreted as limited to surgical methods pursuing a therapeutic purpose. It could not give an authoritative once and for all definition of “surgery” since the scope of what is regarded as surgery may change over time, and the relevant criterion should be handled on a case by case basis. However, in answer to the first question, a claimed imaging method in which, when carried out, maintaining the life and health of the subject is important and which comprises or encompasses an invasive step representing a substantial physical intervention on the body which requires. professional medical expertise to be carried out and which entails a substantial health risk even when carried out with the required professional care and expertise, is excluded from patentability as a method for treatment of the human or animal body by surgery pursuant to a.53(c) EPC.

In response to the second question, the claim cannot be left to encompass an embodiment which is excluded by a.53(c). Omission of the excluded step should be considered on a case by case basis, but e.g. claims to operation of devices without requiring a surgical step have been held allowable, see T 0245/87, T 0789/96 and T 0329/94, compare T 0082/93. Expressions such as “predelivered” and “preimplanted” have been employed to make clear that the feature pertaining to that step was not part of the claimed invention. However, the remaining requirements of the EPC and in particular a.123(2) and in opposition cases a.123(3) must still be fulfilled.

As regards the third question, a claimed imaging method does not fall within the prohibition merely because during a surgical intervention the data obtained by the use of the method immediately allows a surgeon to decide on the course of action to be taken during the surgical intervention.

It will be appreciated that the function of the Enlarged Board is not in itself to decide the outcome of the appeal, but merely to answer the legal questions put to it by the referring board. The case will now be returned to that board, who will have to decide in the light of the answers given and any amendments filed by the applicants what claims might eventually be allowed.

Comments

The present decision provides useful clarification of the relevant law, but probably does little more than to provide more authoritative support for the general approach already adopted by the EPO. It is believed that the number of applications where the outcome will be materially different as a result of the present decision is likely to be small. However, it will be interesting to see what claims are eventually allowed in this case.

The prohibition under the EPC is to surgical methods rather than surgical apparatus so that in a situation such as the present it may be desirable to present apparatus claims, in this case apparatus for MRI imaging including firstly apparatus for administration of 129Xe to the human body and secondly MRI apparatus configured to supply exciting pulses with a large flip angle and to produce a resultant MRI image. The argument could then be that there would be no motivation to bring together these pieces of apparatus but for the discovery of the new imaging method. For an example of this approach compare the granted claims in EP-B-0436717 (Maddox, Cobe Lab) with the granted claims of the equivalent US-A-5474772, for a more detailed explanation see Fundamentals of Patent Drafting, Paul Cole, CIPA, London, 2006 at pp. 218-222.

The use claim has not been considered by the Enlarged Board, but it would appear in principle to be allowable. The recitation of methods of treatment or diagnosis merely specifying performance of the previously defined method may be too general, however, and it would be expected that the EPO would require further definition characteristic of potential disease states e.g. for the purpose of providing clinically useful images of the left and right pulmonary veins and associated capillaries, the left atrium and left ventricle, the myocardium, the ascending aorta, the coronary arteries, the aortic arch, the descending aorta, the left and right subclavian arteries, and the left and right carotid arteries as recited in the description of the application.

Posted in Non-U.S. Practice | Tagged , , , , | Leave a comment