Irides: Weekly patent litigation update

The Irides Weekly Update is our round-up of patent litigation news highlights from around the world. Taking its name from the plural of “iris” - a nod to the ability of Irides to see what’s happening around the world.

Our latest edition - 4 August 2023 - is below:

UK

UK Court finds patent invalid for lack of plausibility across the scope of the claims

On 24 July 2023, Meade J handed down his decision in the dispute between Teva and Grünenthal concerning EP (UK) 1 457 208 (the “Patent”) which relates to a formulation of testosterone undecanoate (“TU”) with castor oil and benzyl benzoate for treating hypogonadism. The Judge dismissed the obviousness attack, but found the Patent to be insufficient for lack of plausibility and therefore invalid.

The relevant product claims in issue concerned a TU formulation in a vehicle comprising 25-45% castor oil and an unspecified amount of benzyl benzoate (Claim 1), and a claim dependent on Claim 1 comprising 55-65% benzyl benzoate (Claim 4) (the “Product Claims”). The presence of an oil and co-solvents in the vehicle is essential for achieving a “depot effect”, i.e. a slow release of the drug into the body which meant that patients could have longer intervals between injections whilst keeping their testosterone levels in the normal range. The relevant method claims in issue claimed a method of administrating the TU formulation using 2 loading doses at 6-weekly intervals followed by a maintenance phase of injections in intervals of at least 9 weeks (Claim 7), or the same loading doses following by injections at 10 or 12 weekly intervals (Claim 16) (the “Method Claims”).

Grünenthal markets a formulation of TU covered by the Patent under the brand name Nebido®.

Obviousness over the prior art

Teva pleaded obviousness over a piece of prior art referred to as “von Eckardstein”, read in light of two papers referenced therein (“Nieschlag” and “Behre”), all of which related to a series of clinical studies for a TU in castor oil formulation for treating male hypogonadism. It was proven at trial that the TU formulation in the prior art was the same as Nebido.

The first issue concerned the Product Claims, and whether the disclosure in von Eckardstein of the TU preparation being “1000mg TU dissolved in 4 ml castor oil” was a complete disclosure, or whether it included an unspecified co-solvent and if a co-solvent were included, the identity of the co-solvent and the amount.    Teva’s case was that the skilled person would know that castor oil was far too viscous to be injected into people on its own and therefore a co-solvent was necessarily included in the formulation.   Teva argued, based on the commercially available formulations at the priority date, that benzyl benzoate was the most obvious partner for castor oil and from then on, routine tests would reveal the ideal ratio of castor oil to benzyl benzoate in order to yield an optimal viscosity for the formulation whilst ensuring the TU remained dissolved. It argued that the skilled person would reverse-engineer a formulation which had a similar overall profile to a dose response curve in the cited prior art.

Meade J accepted that upon testing the solubility of TU in castor oil the skilled team would quickly discover there must be a co-solvent present and that benzyl benzoate is one option the skilled formulator would try. However, he considered that Teva’s argument that the skilled person would seek to reverse-engineer the prior art was driven by impermissible hindsight.

The second issue concerned the Method Claims, and whether it would be obvious for the skilled team to alter the dosing regimen disclosed in the prior art to arrive at the Patent. Teva’s case was that the skilled team would understand the prior art to disclose 4 loading doses, which achieved supraphysiological levels of serum testosterone after the 3rd and 4th injections. Therefore it would be obvious to reduce the number of loading doses down to two.  The Judge again rejected this argument as being tainted with hindsight; the skilled team would not know that two loading doses were better than four, and there were other posology options the skilled team would try.

Insufficiency

Considering insufficiency, the Judge applied the three-step test from Fibrogen which, at least until the Supreme Court determines otherwise, represents the approach to determining the sufficiency of claims to a class of compounds:

1. What falls within the scope of the claimed class?;
2. What does it mean to say that the invention works?;
3. Is it possible to make a reasonable prediction that the invention will work with substantially everything falling within the scope of the claim?

There was no dispute on question 1. On question 2, Meade J referred to the specification to find that the invention must provide physiological levels of testosterone for a prolonged period of time (and achieving the claimed dosing intervals for the Method Claims).

The real dispute turned on question 3. The Judge accepted Teva’s submission that the claims (as interpreted by the teaching of the specification) allowed for substantial variation in parameters such as the amount of TU injected, and the percentages of castor oil, benzyl benzoate and other excipients in the vehicle, and found that variations in these parameters would have knock-on effects on solubility, viscosity, partition coefficient and ultimately on the depot effect. All the claims in issue were therefore insufficient for lack of plausibility.

Finally, Meade J considered the decision of the German Federal Patent Court which had revoked the German designation of the Patent for obviousness (lack of plausibility was not in issue) earlier in the year. The Judge concluded that Teva’s obviousness attack and the evidence adduced in the German proceedings was quite different to the UK case, therefore he was able to reach a different conclusion.

BRAZIL

Federal Court of Appeals clarified that divisional applications may be filed during the appeal process

On 25 July 2023, the Federal Court of Appeals clarified the timeframe within which an applicant may file a divisional application. Under Article 26 of the Brazilian Patent Statute, a divisional application can be filed until the “end of the examination”. Previously, the Brazilian Patent and Trademark Office (BRPTO) interpreted the “end of the examination” to mean a first instance decision; appeals were considered to be re-examination and so divisional applications could not be filed during the appeal stage.

The Federal Court of Appeals ruled that the Brazilian Patent Statute does not impose a limitation on the meaning of the “end of the examination” and in imposing a limitation, the BRPTO had exceeded its normative powers under the BRPTO Ordinance #30/2013. Accordingly, applicants can file divisional patent applications during the appeal stage even if there has been a negative decision at first instance.

DENMARK

Consultation open for comments on future reimbursement status of opioids

Denmark’s Reimbursement Committee (which advises the Danish Medicines Agency on matters regarding reimbursement) has presented a proposal that would change the reimbursement status of opioids in the future. The proposal is based on the Reimbursement Committee’s view that opioids should not be the first choice for treatment and that their use should be limited to selected patients who do not respond to non-medical treatment or non-opioid pain relief.

The proposal is that rather than certain opioids retaining a general reimbursement status (whereby all citizens receive reimbursement), those opioids should be subject to conditional reimbursement (whereby reimbursement is only granted in certain cases e.g., the treatment of specific diseases in certain patient groups).

Affected companies may submit comments on the proposal by email to medicintilskudsnaevnet@dkma.dk by 21 September 2023.

UK

Court of Appeal dismisses generics’ appeal regarding obviousness of patent for use of mirabegron for treatment of overactive bladder

On 25 July 2023, the Court of Appeal handed down its decision concerning the validity of Astellas’ European Patent (UK) 1 559 427 B1 (the “Patent”) to mirabegron for use in the treatment of overactive bladder (“OAB”).

Mirabegron is a β3-adrenoceptor (“β3-AR“) agonist (i.e. a substance that binds to and activates certain receptors on cells) which results in relaxation of the bladder smooth muscle, expanding the bladder’s capacity and relieving patient symptoms.

First Instance

At first instance, the claimants, Teva and Sandoz, challenged that the validity of Astellas’ patent did not contest their infringement of the patent. The main issue at trial was whether the Patent was valid over a single piece of prior art which disclosed a series of compounds, according to a Markush formula. The compounds were described as being therapeutic agents for diabetes mellitus and as having anti-obesity and anti-hyperlipemia actions due to selective stimulation of β3-AR (i.e. agonism). The prior art disclosed six example compounds, including mirabegron. Numerical data was provided in relation to one of the other example compounds for testing in a hyperglycaemic mouse model. The treatment of OAB was not discussed in the prior art, neither was there any numerical data demonstrating the selectivity of the compounds for β3-AR.

The Patent was held to be valid over the prior art by the first instance judge because it was not obvious to try mirabegron as a treatment for OAB with a reasonable expectation of success. This was due, in part, to the skilled team’s lack of confidence in β3-AR agonism as a potential therapy for OAB and the lack of disclosure on this in the prior art.

Appeal

On appeal, Teva and Sandoz contended that the first instance judge had erred in the application of the law on obviousness; in particular, in his assessment as to whether the Patent solved the problem to which it was addressed. On the basis that the Patent only provides data from rat models for OAB (i.e. no human clinical trial data or data from human tissue assays was provided), the appellants argued that the first instance reasoning depended on two uncertainties that the Patent had failed to solve: (1) the uncertainty regarding β3-AR agonism for treating OAB without human clinical trial data; and (2) the uncertainty as to whether mirabegron was a human β3-AR selective agonist or a sufficiently potent agonist.

The Court of Appeal did not accept these arguments for two reasons. First, it was not the case that the first instance judge had held the Patent to be inventive because it overcame the technical problem of side effects associated with cross-reactive β3-AR agonists; indeed, at first instance, the patentee had accepted that the Patent does not disclose mirabegron’s selectivity for β3-AR. Instead, the judge had found that, having read the prior art in light of the common general knowledge, it was not obvious to try mirabegron as a treatment for OAB with a reasonable expectation of success.

Second, the Court of Appeal held that the question of obviousness does not depend on the amount of evidence presented in the specification. Provided that the Patent makes it plausible that mirabegron is efficacious for the treatment of OAB (which the appellants accepted), then obviousness should be assessed in the normal way, i.e. whether the prior art read together with the common general knowledge made it obvious to try mirabegron as a treatment for OAB with a reasonable expectation of success. The Court of Appeal considered that the first instance judge had done so and thus saw no reason to interfere with his judgment, thereby dismissing the appeal.

UPC

New Technical Judges Appointed

Following the decision of the Administrative Committee dated 2 June 2023, 21 new technically qualified judges have been appointed at the UPC.  The judges will have all taken their oath by 5 September 2023.  More information can be found here.