Napp N Sandoz, Ratiopharma- Oxycodone patents Valid in UK

Broadly, the two patents in suit are for a 12-hour controlled release form of oxycodone. The claims alleged to be infringed by the Cimex product are for barrier-type controlled release forms. The barrier-type form specifically described is made by the use of extrusion spheronisation, one of a number of well-known way of making small spherical particles. The description also includes matrix-type forms .


Generic’s tablets of oxycodone contained small particles made up of a number of layers (supplied to the generic companies by Cimex). The core of these particles is made from sugar crystals. There is then an inner layer of made up of oxycodone hydrochloride (83% wt), hydroxypropylmethyl cellulose (HPMC, about 8% wt) and talc/macrogol (about 9% wt). A further polymer layer contains ethyl cellulose, hydroxypropylcellulose and propylene glycol. The polymer layer controls the release of the oxycodone hydrochloride in the inner layer. A further outermost layer contains about 96% wt oxycodone hydrochloride and about 4% wt HPMC. About 20% of the total weight of oxycodone hydrochloride is in the outermost layer.

In the generics’s product 20% of the oxycodone is on the outside of the particles and 80% is within. The 20% will be released more or less immediately whereas the 80% will be slow-released through the polymer layer. By contrast the key difference from what is specifically described in the patents is that in the latter all the oxycodone is inside a polymer layer and will be control-released.

Infringement:
Ratiopharm and Sandoz- did not admit that the Cimex tablets comprised "spheroids" or a "spheronising agent". They pleaded that the term "spheroids" denoted spherical granules manufactured by spheronisation and that none of the excipients constituted a "spheronising agent". The inner and outer layers contain HPMC, about 8 wt% and 4 wt% respectively. They say that the water-soluble HPMC serves as a binder and is not a spheronising agent
Court- interpreted "spheroid" was not limited to the process by which the product was made and also stated that water soluble polymer such as HPMC was suitable for four out of the five spheronisation processes known at the priority date for producing spheroids for a controlled release formulation: (1) fluidised-bed granulation; (2) rotor granulation; (3) extended wet granulation; and (4) non-pareil beads (the Cimex process).Hence the generic process infringed the claims.
Ratiopharm and Sandoz- argued that the claims do not extend to a form of dosage in which some of the oxycodone is on the outside of the coating. This question arises because the Cimex product has an external layer on its spheroids consisting of about 20% of the drug, which is released immediately, the remaining 80% being within the coating which controls its release.
Court - concluded that there is nothing in the claim language that excludes a tablet which has all the characteristics it sets out, but with the additional feature of an external application of oxycodone. There is also nothing in the teaching in the patent to suggest that such a tablet was intended to be excluded. Nor is there any commercial or technical reason for thinking that the patentee would have wanted to exclude an otherwise infringing article with such an additional feature.

Further with respect to claimed dissolution profiles, the issue between the parties was - does the claim call for the whole of the test procedure in the USP, including the acceptance test, to be carried out so that the claim only covers that which passes the acceptance test, or is it sufficient if an individual dosage form passes the test? The point matters because only a modest (7%, nonetheless significant) proportion of the Cimex tablets have dissolution rates within integer 1(d). If the true construction of this feature requires compliance with the USP acceptance requirements there is no infringement, even though a proportion of the tablets, as individual tablets, do comply with the rates set out in the claim.
Court concluded that the claim is for a dosage form. It is a dosage form which must past the test. On the r/S construction one would have to test at least 6 tablets and possibly up to 24 tablets. And one could then decide whether the batch of tablets from which these were taken satisfy the criteria. Hence the generic falls within the scope of the claims.
Invalidity:
Sandoz and ratiopharm said the patents were invalid in respect of added matter under Article 123 of the European Patent Convention ("(2) A European patent application or a European patent may not be amended in such a way that it contains subject-matter which extends beyond the content of the application as filed") and under the Patents Act 1977 ("Since our provisions mean the same as Art 123(2) there is no point in referring to them"). The argument of invalidity was that parts of the specification and/or claims of 730 had not been disclosed clearly and unambiguously in Napp's PCT application and/or that they did not provide a technical contribution.
However court concluded "A feature which has not been disclosed in the application as filed but which has been added to the application during examination and which, without providing a technical contribution to the subject-matter of the claimed invention, merely limits the protection conferred by the patent as granted by excluding protection for part of the subject-matter of the claimed invention as covered by the application as filed, is not to be considered as subject-matter which extends beyond the content of the application as filed within the meaning of Article 123(2) EPC. The ground for opposition under Article 100(c) EPC therefore does not prejudice the maintenance of a European patent which includes such a feature"

UK appeal court also addressed the opposite verdict reached by german courts earlier and stated that “We are not persuaded by either of these decisions, even though we give great respect to the decisions of the German courts”