Infringement of SPCs by combination products

Philippe de Jong from Altius in Brussels has directed us to a couple of articles written for the EPLAW patent blog (http://www.eplawpatentblog.com/) relating to SPCs and combination products.

The articles are entitled:

SPCs and combination products - Infringement Issues, by Philippe de Jong

SPCs and combination products - Validity Issues, by András Kupecz (Simmons & Simmons)

Philippe also provides three recent decisions concerning losartan and SPCs, two of which are Belgian decisions (and for which he has provided English translations), and the third from the French courts. We'll put them onto the SPC resources page too.

English summaries of the 3 decisions are as follows:

Brussels court of appeal, 23 February 2010, Du Pont et al. / Mylan, losartan SPC, decision in summary proceedings (appeal) (English translation here)

According to the Brussels court of appeal, the scope of protection of the SPC for the active ingredient losartan does not, at first sight ("prima facie"), extend to a generic version of the medicinal product Cozaar Plus® (containing the active ingredients losartan and HCTZ) under Article 4 of the SPC-Regulation. The main reason raised by the court is that, since the combination of losartan and HCTZ was itself protected by an SPC, a medicinal product containing that combination could not infringe the SPC for losartan alone. According to the court, this would appear to run counter with Articles 3(c) and (d) of the SPC-Regulation.


Pres. Brussels commercial court, 12 February 2010, Du Pont et al. / Mylan, losartan SPC, decision in summary proceedings (first instance) (English translation here)

According to the President of the Brussels commercial court, the scope of protection of the SPC for the active ingredient losartan, whose duration had been extended pursuant to Article 36 of the Paediatric Regulation 1901/2006, does not at first sight ("prima facie") extend to a generic version of the medicinal product Cozaar Plus® (containing the active ingredients losartan and HCTZ). The main reason raised by the court is that, since the paediatric extension was applied for and granted only for the losartan-SPC and not for the separately obtained "losartan + HCTZ"-SPC, the combination product Cozaar Plus® could not benefit from the paediatric extension of the losartan-SPC. Consequently, generic versions of Cozaar Plus® could not fall under the scope of protection of the losartan-SPC either.


Pres. Paris district court, 12 February 2010, Du Pont et al. / Mylan, losartan SPC, decision in summary proceedings (first instance)

According to the President of the Paris district court, the basic patent for losartan covers any product comprising losartan, including a product comprising losartan and another product such as a diuretic, like HCTZ. Since pursuant to Article 5 of the SPC-Regulation, an SPC confers the same rights as the basic patent and since pursuant to the Article 4 of the SPC-Regulation the SPC protects any subsequently authorised use of the product as a medicinal product, the combination product losartan+HCTZ falls under the scope of protection for the losartan-SPC. The fact that the paediatric extension was only granted for the losartan SPC and not for SPC for the combination product, was not held to be relevant. According to the court, the extended protection of the basic patent and the subsequent SPC, could only lead to the conclusion that any medicament containing losartan as an active ingredient amounted to an infringement.
As to the prima facie validity of the SPC-extension, the court held, inter alia, that the relevant provisions of the SPC-Regulation and Regulation 1901/2006 do not specify that the MAs need to have been obtained at the time of the filing of the application. The paediatric MAs must have been applied for on the day of the filing of the application, but can be communicated whilst the application is under examination.

More questions to the Court of Justice

A few months ago, we reported on Medeva's appeal against the UK IPO's decision to refuse an SPC application here

The SPC blog has found out that the Court of Appeal for England and Wales will be referring questions to the ECJ on the meaning of Article 3a and 3b of the SPC regulation, in the context of combination products. We haven't seen the questions, yet, but when we do you'll be the first to know.

More on active implantable medical devices..

Thanks to Alice de Pastors for more information on the fate of SPC applications on Yttrium-90 Glass Microsperes (see our post on 15th April here).

Alice tells us that the Dutch SPC 300226 was granted but then lapsed for non payment of annual fees. In other EU countries there were refusals in Belgium, Denmark, Italy, Sweden, and surrender in France.

US Court of Appeals Decides Enantiomer Patent Term Extension Case

We don't usually report on US issues, but Jeffrey S. Boone, Vice President, Intellectual Property, for Covidien (Hazelwood, Missouri, US) has kindly sent us this update on patent term extensions in the US.

"In the United States, the Court of Appeals for the Federal Circuit (CAFC) today (2010 May 10) issued its decision in the case of Ortho-McNeil Pharmaceutical, Inc. v Lupin Pharmaceutical, Inc. The court decided that the previous approval of a racemic mixture does not prevent a patent term extension for a single isomer of the racemic mixture.

US 4,382,892 claims ofloxacin, an antibiotic which is a racemic mixture of equal amounts of two stereoisomers (enantiomers). The patent was granted in 1983 and the US FDA approved the commercial marketing of ofloxacin (FLOXIN®) in 1990. In 1991 a subsequent patent, US 5,053,407, was granted for levofloxacin, one of the enantiomers in ofloxacin. In 1996 the FDA granted marketing approval for levofloxacin, which has been sold under the proprietary name LEVAQUIN®.

The plaintiff submitted an application for a Hatch-Waxman patent term extension for the ‘407 patent, which claims the single enantiomer. With full knowledge that the racemic mixture had been previously granted marketing approval, the FDA decided that the marketing approval of levofloxacin (the single enantiomer), was the “first” permitted commercial marketing or use of the “product”, as defined under 35 USC 156(f)(1). Thus, the FDA decision, which was consistent with several similar prior cases, was essentially that the racemic mixture and the single enantiomer were not the same “product”, as defined by the statute.

In litigation that resulted from the defendant’s filing of an ANDA (an application for a generic version of LEVAQUIN), the defendant, Lupin, argued that an enantiomer is half of its racemate, and thus the enantiomer was a component of the previously approved drug. However, the district court declared on 2009 April 30 that the patent term extension was valid.

Now, the court of appeals has affirmed the district court. The court quoted one of the witnesses who stated “in each and every instance in which it has considered the question, the FDA has described a racemate as a single active ingredient, distinct from its enantiomers, and each enantiomer as a single active ingredient distinct from the other and from the racemate”."

You can read the case here.

High Court upholds IPO's decision on Circadin

In December 2009, we reported that the Intellectual Property Office refused an SPC application for Circadin on the grounds that the application did not comply with Article 3(d) of the SPC Regulation.

The High Court has upheld the IPO's decision. Following a review of the provisions of Regulation 469/2009 and case law of the Court of Justice (Pharmacia, MIT and Yissum), Arnold J. held that "Yissum is fatal to Neurim's case on this appeal". He also considered that the interpretation of Article 3(d) is acte claire.

You can read the decision here.

SPCs on adjuvants??

The SPC blog has found out that a couple of patent offices, Italy and Slovenia, have granted SPCs on vaccine adjuvants (generally vaccine components that modify the immune response to an antigen). We recall from the SPC blog event in January that France had refused such claims, and it wasn't looking too good elsewhere for those seeking this sort of protection.

The medicinal product in question was a combination of antigen + adjuvant, and SPCs were granted to both the adjuvant per se and to the (antigen + adjuvant) as a combination of active substances.

All of this must be considered within the context of the decision in the ECJ Case C-431/04 (MIT) which related to a combination of an active plus a bioerodible matrix that enabled the active to be administered in a therapeutically relevant way. The ECJ decided that:

Article 1(b) of Council Regulation No 1768/92 of 18 June 1992 ...must be interpreted so as not to include in the concept of ‘combination of active ingredients of a medicinal product’ a combination of two substances, only one of which has therapeutic effects of its own for a specific indication.

Does a vaccine adjuvant have a therapeutic effect of its own for a specific indication? A vaccine adjuvant, which itself has some immunological/ physiological effect on a host, might at least be considered to be more of an active substance than a matrix to allow slow release.

Let's throw into the mix (not literally) that some adjuvants for vaccines are being considered as monotherapies in their own right, such as CpG for cancer ...

Moreover, it's an interesting one for patent attorneys and their regulatory teams. Do you argue that an adjuvant is an active, which may be necessary if trying to obtain an SPC on a combination of an old active with new adjuvant, for example. Or do you argue that the adjuvant is a mere excipient to assist in the regulatory process?

If anyone has any other SPC related information on SPCs granted or refused on adjuvants, please do share them with us.

Romania's SPC fees and forms

On 31 March 2010 the Romanian Patent and Trade Mark Office issued Regulation No. 111. This Regulation adds two new points to Article 6 of Regulation No. 146 on Supplementary Protection Certificates for Medicinal and Plant Protection Products from December 28, 2006. According to a news item from Balkan-based IP practice Petosevic:

"The newly added point 6 provides that the official fee for the examination of a request for a 6-month extension of the supplementary protection certificate for medicinal products for pediatric use is EUR 500 (USD 682), the same as for the examination of a request for granting an SPC for other medicinal products.

The newly added point 7 provides that the official fee for the 6-month extension of an SPC for medicinal products for pediatric use, as per the provisions of Council Regulation (EEC) No. 1768/92 with further amendments, is EUR 1,400 (USD 1,913).

On the same date ... the Romanian PTO issued Regulation No. 112, which establishes the standard form to be used for requesting the extension of an SPC for medicinal products for pediatric use.

These two new regulations establish formal rules for practices regarding the SPCs that were not formerly regulated by the PTO".

Genzyme Biosurgery v BIE: English translation

Following on from our post on Thursday 15th April concerning medical devices, attached is an English language version of the Genzyme Biosurgery v BIE decision. Many thanks to Kathryn Nicholls at Mewburn Ellis LLP for this.

Jodosulfuron dispute: hearing this Thursday

In June last year The SPC Blog reported on a German reference for a preliminary ruling from the Bundespatengericht to the Court of Justice of the European Union on the interpretation of Art. 3(1)(b) of Council Regulation 1610/96 regarding the creation of a supplementary protection certificate for plant protection products. This reference is Case C-229/09 Rechtsanwaltssozietät Lovells v Bayer CropScience AG (jodosulfuron) and the single question referred for a ruling is this:

"For the purpose of the application of Article 3(1)(b) of Regulation (EC) No 1610/96 of the European Parliament and of the Council of 23 July 1996 concerning the creation of a supplementary protection certificate for plant protection products, must account be taken exclusively of a marketing authorisation under Article 4 of Directive 91/414/EEC, or can a certificate also be issued pursuant to a marketing authorisation which has been granted on the basis of Article 8(1) of Directive 91/414/EEC?".

The hearing before the Court takes place this Thursday, 22 April at 11.00am.

SPCs, actives and medical devices

Recently, we posted a German Federal Patent Court decision which overruled a decision of the German Patent and Trademark Office, and granted an SPC to an implantable medicinal device (see link - Yttrium-90 Glass Microspheres). In light of questions we have received on this issue the SPC Blog asks whether any of its readers is aware of further decisions on SPCs involving medicinal devices.

By way of background, the issue is as follows.

Article 2 of SPC Regulation EC 469/2009 stipulates that:

"Any product protected by a patent in the territory of a Member State and subject, prior to being placed on the market as a medicinal product, to an administrative authorisation procedure as laid down in Directive 2001/83/EC of the European Parliament and of the Council of 6 November 2001 on the Community code relating to medicinal products for human use or Directive 2001/82/EC of the European Parliament and of the Council of 6 November 2001 on the Community code relating to veterinary medicinal products may, under the terms and conditions provided for in this Regulation, be the subject of a certificate."

[A product according to Article 1 of the SPC regulation is any active ingredient or combination of active ingredients of a medicinal product].

What does the underlined text mean? Does it mean that only a product specifically approved under Directive 2001/83/EC or 2001/82/EC may be subject of an SPC, or does it allow for an SPC to be granted for an active approved under some other EC legislation, and where the active component has undergone the same level of scrutiny as required by in Directive 2001/83/EC or 2001/82/EC.

The latter situation may arise in the medicinal devices Directives 93/42/EC (for Medicinal Devices) and 90/385/EEC (for implantable medicinal devices).

For example, Article 1(3) of Directive 93/42/EC indicates that medical devices containing actives are generally covered by the medicinal device directive and would not be authorised under Directive 2001/83/EC or 2001/82/EC. [The exception is where the device and the medicinal product form a single integral product which is intended exclusively for use in the given combination and which is not reusable, in which case Directives 2001/83/EC or 2001/82/EC apply].

Directive 93/42/EC specifies, in paragraph 7.4 of Annex 1,that:
"Where a device incorporates, as an integral part, a substance which, if used separately, may be considered to be a medicinal product as defined in Article 1 of Directive 65/65/EEC and which is liable to act upon the body with action ancillary to that of the device, the safety, quality and usefulness of the substance must be verified, taking account of the intended purpose of the device, by analogy with the appropriate methods specified in Directive 75/318/EEC [now Directive 2001/83/EC]. Similar language is found in Article 1(3) and paragraph 10 of Annex 1 of Directive 93/385/EEC.

Thus it would appear that an active component of a medicinal product whose approval is governed by the medicinal devices Directives should to be assessed at the same level of rigour as an active agent covered by Directives 2001/83/EC or 2001/82/EC. The need for equally stringent testing of active ingredients approved under different directives makes perfect sense, but does that fact alone open the door to SPC protection for the product?

Arguably it should. It appears to be unfair that SPC protection would only be available to actives that have been approved under Directives 2001/82/EC or 2001/83/EC, and that a new active specifically delivered by a device but approved under the medicinal devices Directive 93/42/EC (for example), could not take advantage of the SPC provisions.

The German Federal Patent Court in the Yttrium-90 Glass Microspheres case considered the level of testing required by the medicinal devices Directives allowed the product to conform to the administrative authorisation requirement of Article 2 of SPC Regulation EC 469/2009.

A similar conclusion was arrived at by the Court of The Hague in 2004 in Genzyme Biosurgery v. BIE (if anyone has an English translation of this decision we'd love to see it).

However, a court might consider that it was not able to interpret Article 2 of the SPC regulation more broadly than approval under Directives 2001/82/EC and 2001/83/EC per se. It might also be argued – at a stretch - that assessment of safety "by analogy" with Directive 2001/83/EC is not necessarily assessment at the same standard as under by Directive 2001/83/EC.

If you have other examples in the device area we would be interested to find out.

You can post any thought as a Comment below.