C5 second medical_use_patents_presentation_29_january_2014

© 2014 Innovate Legal Services Limited

Second and further medical use patents:enforcement perspective

Dr Duncan CurleyDirector and Head of Patents, Innovate Legal

C5 Pharma & Biotech Patent Litigation Conference - 29 January 2014


Second and further medical use patents:enforcement perspective

Outline of presentation

1.Proving infringement

2.Regulatory position and skinny labelling

3.Some caselaw

4.Conclusions


Proving infringement

It is necessary for manufacturers of generic medicines to provide detailed instructions on the use and dosage of their products.

….but including a patented indication on a product label may give rise to liability for direct infringement.

Generic manufacturers will usually pick up on patented uses during their freedom to operate searches, so they are generally alert to this issue.


Regulatory position

Directive 2001/83/EC (as amended) – Article 11

For authorisations under Article 10, those parts of the summary of product characteristics (SmPC) of the reference medicinal product referring to indications or dosage forms which were still covered by patent law at the time when a generic medicine was marketed need not be included.

“Skinny labelling” (removing or ‘carving out’ the patented use from the label) is therefore an option.


Regulatory position

2012 Guidance from CMDh (European Co-ordination Group for Mutual Recognition and Decentralised Procedures – Human) – see:http://www.hma.eu/fileadmin/dateien/Human_Medicines/CMD_h_/Questions_Answers/CMDh-279-2012-Rev0-

2012_10.pdf.

‘Usage’ Patents claim novel ‘uses’ (indications, formulations, routes of administration, dosage schedules, patient populations etc.) for known / already patented active substances. To the extent that the ‘usage’ patent satisfies the requirements for a valid patent, it confers an independent full period of patent protection in relation to the claimed invention.


Regulatory position

Guidance from CMDh (ctd).

This can give rise to potential patent infringement in the event that a generic of an innovator product for which the initial patent protection period has expired but which is still protected by a ‘usage’ patent is authorised by a competent authority which would normally require the generic authorisation to conform to that of the innovator with respect to the summary of product characteristics and package leaflet and labelling as appropriate.


Regulatory position

Guidance from CMDh (ctd).

Is it possible not only to delete the patented indication, but also to change/delete further sentences in other sections directly connected to this patented indication, e.g. in posology, contra-indications or warnings?

Answer: The Directive states only the exclusion of information referring to indication and dosage forms. Any other deletion connected to the patented indications or dosage forms must be properly justified and discussed with the member state concerned.

Some care therefore needed when skinny labelling!


Contributory infringement - background

For example, section 60(2) of the UK Patents Act 1977 [simplified for present purposes]:

A person also infringes a patent if he supplies or offers to supply a person…with any of the means relating to an essential element of the invention for putting the invention into effect when he knows, or it is obvious to a reasonable person in the circumstances that those means are suitable for putting, and are intended to put, the invention into effect….



Example: UK supply chain [for hospital products]:

Generic pharmaceutical company supplies wholesaler

wholesaler supplies hospitals

where products are used by doctors to treat patients



Pharmaceutical product labels and “contributory infringement” - caselaw:

“It is sufficient if it is shown that the invention [i.e. the patented use] will be put into effect by some users [e.g. some doctors]”.

“ One would only disregard maverick or unlikely uses of the thing”

- per Jacob, L.J. in Grimme Maschinenfabrik GmbH v Scott (English Court of Appeal decision)



Grimme applied in KCI Licensing Inc. v Smith & Nephew plc (another English Court of Appeal decision):

• The question is what the supplier knows (or ought to know) about the intention of the person who is in a position to put the invention into effect, i.e. the doctor.

• It is enough to prove contributory infringement if the supplier knows (or it is obvious to a reasonable person in the circumstances) that some ultimate users will intend to “use” the product so as to infringe.

• Thus, it is the intention of the ultimate user (i.e. the doctor) that “counts”.


Caselaw

Ribavirin - District Court of Düsseldorf, 2004

The patentee’s claim covered the use of ribavirin for the treatment of HCV infections.1.The use of ribavirin for the manufacture of a pharmaceutical composition for treating a patient having chronic hepatitis C infection to eradicate detectable HCV-RNA

2.by a method comprising administering an effective amount of ribavirin in association with an effective amount of interferon alpha

3.for a time period of 40-50 weeks

4.wherein the patient is one having failed to respond to a previous course of interferon alpha therapy, characterised in that

5.the patient has a viral load of greater than 2 million copies per ml of serum as measured by HCV-RNA quantitative PCR

6.of a HCV genotype type 1 infection.


Caselaw

Ribavirin - District Court of Düsseldorf, 2004

The package insert (SmPC) was presented as proof of direct infringement. This specified ribavirin co-administered with alpha interferon, but the court found that the main use intended was ribavirin monotherapy and furthermore there was no specific reference in the SmPC to the patient group defined in the claim.

Conclusion: no direct infringement, even though the court noted that “…it cannot be excluded that…patients belonging to the special subgroup described in the patent in suit are also treated [with the Defendant’s product]”.


Caselaw

Ribavirin – Schering v Teva, District Court of The Hague, 2010

The Dutch court considered Teva’s SmPC to their ribavirin product, but again in the context of direct infringement.

Teva had skinny labelled and there was no reference to the claimed patient group.

Conclusion: no direct infringement. Teva’s SmPC tracked the use of ribavirin in the prior art. However, the Dutch court observed that the conclusion might have been different if evidence had been provided that Teva’s ribavirin would have been prescribed for the patient sub-group because of information given elsewhere in the SmPC.


Caselaw

Clopidogrel

In 2008, the data exclusivity period for the Sanofi anti-coagulant product Plavix® (containing the API clopidogrel) ended.

Although Sanofi had continuing patent protection for a specific salt form of clopidogrel (the hydrogen sulphate), a number of generics subsequently sought to enter the market with products based on alternative clopidogrel salts.

Sanofi had a further patent which claimed (inter alia) the use of clopidogrel in combination with aspirin (European patent no. 0,881,901).


Caselaw

Clopidogrel

European patent (DE) no. 0,881,901 (Sanofi)

In Germany, Sanofi sued ratiopharm and Hexal in September 2009 for infringement of European patent (DE) no. 0,881,901, based on information in the generic companies’ Patient Information Leaflet (PIL) and SmPC suggesting the combined use of clopidogrel with aspirin.

However, because serious doubts were raised about the validity of the patent at the preliminary injunction hearing, no injunction was granted.


Caselaw

Losartan

4 main indications on the label of the originator product, Cozaar®.

European patent (UK) no. 0,253,310 (Merck). SPC expired on 1 September 2009; extended (after a struggle) to 1 March 2010 by paediatric extension.

Numerous other Merck patents to various uses of losartan ran on past 1 March 2010, including European patent nos. 0,533,840, 0,966,282 and 0,636,027.

Generic competitors launched with a variety of skinny labels, some bearing 1, 2, 3 and 4 indications…no action taken (despite the high value of the product).


Conclusions

Clinical research has advanced and so new medical uses now recognised and explored earlier in product lifecycles.

Second and further medical use patents probably becoming increasingly important in the research-based companies enforcement armoury.

Raises some challenging questions for research-based companies, both in terms of defending validity and of obtaining adequate evidential proof of infringement, but there is developing jurisprudence on contributory infringement and skinny labelling – so watch this space.


Thank you for listening.

Dr Duncan Curley

Innovate Legal

107 Fleet Street

London

EC4A 2AB

Tel: +44(0)20 7936 9056

Fax: +44(0)20 7936 9111

Email: [email protected]

www.innovatelegal.co.uk

C5 second medical_use_patents_presentation_29_january_2014

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