Often, a pharmaceutical does not earn revenue for a company until well into the patent term; sometimes this may be 15 years or more into the term. This delay, coupled with the cost of drug development recently estimated to be on average US$2.6 billion, it is not surprising that pharmaceutical companies seek to extend patent protection for as long as possible to maintain their market exclusivity.

For example, these companies may seek to use “follow-on” patents, which protect new developments or improvements of the original active pharmaceutical ingredient (API), new formulations, derivatives, enantiomeric forms, crystalline forms, purified forms, combinations of APIs, delivery systems, methods of use and methods of production.

While follow-on patenting is sometimes portrayed as an abuse of the patent system by pharmaceutical companies, recent reports found that follow-on patents are not solely held by originator companies and that generic companies also typically file these types of patents.1

Some countries, such as India, prohibit some or all patents on new uses of known substances, enantiomers of known racemic chemical compounds, as well as pure forms of known substances. However, many major industrial jurisdictions, e.g., US, Europe and many other jurisdictions, such as Australia, do allow “follow on” patents, provided that they meet the normal patentability requirements of novelty, inventive step, and industrial applicability.

Despite meeting these requirements, recent studies suggest that follow-on patents are much more likely to attract patent challenges in the US and Europe and additionally indicate that challenges to patent validity have higher success rates in cases involving follow-on patents.2,3,4 Of course, this may be a result of challenges by generic or biosimilar companies looking to enter the market shortly after the original compound (or API) patent expires.

Understanding recent court decisions relating to follow-on patents will assist both innovator and generic companies to secure strong, robust patents to effectively protect their developments in the pharmaceutical area.

Enantiomers of a drug

Claiming a single enantiomer or a specific optical purity of an enantiomer provides protection for the drug itself and all uses thereof.

Claiming a single enantiomer of a drug

Sanofi’s AU 597784 claimed the d-enantiomer of clopidogrel along with salts thereof. In litigation, the Court held that the prior art disclosure of the racemic compound and to each of the enantiomers anticipated the claims to (d)-clopidogrel but did not anticipate the claims to salts of (d)-clopidogrel, as the only disclosures of salts were in relation to that of the racemate. However, the Court took the view that techniques for obtaining enantiomers from a racemate, including the use of diastereomeric salts were straightforward and that the claims were obvious. [Apotex Pty Ltd v Sanofi-Aventis (2009) 82 IPR 416]

The decision in Australia is in contrast to the US decision in which the patent was held to be valid and infringed. The US court was persuaded as to non-obviousness by the unpredictable/unusual properties and the therapeutic advantages of the enantiomer as well as the prior art “teaching away” from the claimed salt. [Sanofi-Synthelabo v. Apotex, Inc. 550 F.3d 1075 (Fed. Cir. 2008)]

Claiming enantiomeric (optical) purity of a drug

AztraZeneca’s AU 676337 claimed “optically pure” salts of (-)-omeprazole. Although “optically pure” was not defined in the specification, in litigation the Judge construed the term to define ≥ 98% enantiomeric excess (e.e.) based on the examples which demonstrated “optically pure” salts having ≥ 98% e.e.

The Court held the claims to be novel since the prior art did not show any “optically pure” (-)-omeprazole or its methods of measurement. The court also held the claims to be non-obvious since there was no convincing evidence led to show that there was a reason to resolve the enantiomers of omeprazole or that such resolution was routine. The court was persuaded that at the filing date of the application, it was expected to be difficult to resolve the enantiomers. [Ranbaxy Laboratories Limited v AstraZeneca AB [2013] FCA 368 (23 April 2013)]

In contrast, in Europe the patent was revoked by the EPO for lack of inventiveness.

Lesson

  • Prior disclosures of a racemic mixture or single enantiomers of a drug may not anticipate claims to salt forms of a racemic mixture or single enantiomers of a drug. However, you may need to show that you have done something more than resolving individual enantiomers in a routine manner or that the enantiomer provides an advantage.
  • Prior disclosures of an enantiomer of a drug may not anticipate claims to a defined optical purity of the enantiomer.
  • Foreseeable and/or actual difficulties associated with obtaining a single enantiomer may be sufficient to support the inventive step.

Claiming crystalline forms of a drug

Claiming a crystalline form of a compound can provide protection for the drug itself and all uses thereof. AU 2002334413 claimed aripiprazole having a specified crystalline structure (identified as ‘Crystals B’) and further characterised by specific physical properties. The Full Court upheld the claims as valid, despite a prior teaching which, if carried out in a particular manner, could result in the claimed product. The Court found that as there are many ways in which the prior art teaching could be carried out that would not result in the claimed product, there was no anticipation. [Bristol-Myers Squibb Company v Apotex Pty Ltd [2015] FCAFC 2]

Lesson

  • If following the instructions in the prior art will not inevitably lead to the particular crystalline form (e.g., if in some cases it will lead to that form and in some cases it will not). The prior publication is not anticipatory. This form of argument can be a strong argument in prosecution and litigation to refute an allegation of inherent anticipation.

Claiming compositions having specific purities of a drug

Claiming a pharmaceutical composition by the level of purity of the drug provides protection for the drug itself and all uses thereof. An example of this is EP1308455 claiming compositions of trastuzumab (Herceptin) with low levels of acidic variants. However, in litigation before the UK courts, the patent was held invalid for anticipation by one of Genentech’s own earlier disclosures teaching a formulation allegedly inherently satisfying the claim or a process which inevitably produced the claimed compositions. In an interesting development, the European Patent Office has recently held that the EP patent is valid over the same prior art used to invalidate the UK patent.

Lesson

  • Be careful of prior disclosures of purification of your drug that may inherently produce the composition you are producing, particularly where your disclosure enables someone to reproduce the process and test the end product.
  • If you have to modify your manufacturing processes to make the final drug composition, you may have a new patent position covering this composition.
  • Some jurisdictions (e.g., Europe) may still require you to show an advantage of this composition over other compositions.

Claiming treatment of patient subpopulations

Often drugs are approved to treat subsets of patients suffering from a condition. This can present an opportunity to obtain further patent protection even if the broader indication has been previously disclosed.

As discussed in our earlier article, Genentech attempted to claim methods of treating patients suffering from rheumatoid arthritis who were non-responsive to TNFα inhibitors using rituximab. The use of rituximab to treat rheumatoid arthritis was previously known.

In an opposition and subsequent appeal in Europe, the patent was revoked for obviousness, with the board providing the following guidance as to what is expected to show non-obviousness of such claims:

  • Evidence that the patient sub-population is not an arbitrary selection (i.e., they represent a population that can be distinguished from the larger population, they have a distinct physiological or clinical situation and there is a functional link between the characteristics of the sub-population and the treatment claimed)
  • Evidence (i.e., data) showing that the treatment works surprisingly well in the claimed sub-population or at least a good reason as to why the skilled person would not have applied the known method of treatment to the sub-population.

Follow-on patents protect new developments or improvements of the subject matter of the basic patent and are part of the business model for both originator and generic companies. Careful consideration of the risks and vulnerabilities of follow-on patents in all stages of a company’s patent strategy is therefore crucial to ensuring strong and robust follow-on patents.

  1. Christie, A. et al (2013) Patents associated with High-Cost Drugs in Australia. PLoS ONE, 8(4): e60812. doi:10.1371/journal.pone.0060812.
  2. Hemphill CS, Sampat BN (2011) When Do Generics Challenge Drug Patents? Journal of Empirical Legal Studies, 8(4): 613–649.
  3. Hemphill S, Sampat BN (2012) Evergreening, Patent Challenges, and Effective Market Life in Pharmaceuticals. Journal of Health Economics 31(2): 327–339
  4. European Commission (2009) Pharmaceutical Sector Inquiry: Final Report.