Divergent patent pathways

The preamble of the Patent Cooperation Treaty (PCT) states the desire of the contracting states “to simplify and render more economical the obtaining of protection for inventions where protection is sought in several countries”.

This is done by filing one application that covers all contracting states. PCT filings therefore confer an enormous simplification for worldwide patent prosecution—in particular, requiring the filing of only a single initial application and allowing cost decisions to be postponed significantly. Many smaller biotechnology companies, often struggling with funding, have taken advantage of this system, which allows limited resources to be allocated more effectively.

From our experience, the key jurisdictions where patents are eventually pursued are nearly always multiple contracting states of the European Patent Convention (EPC) and the US, ie, prosecution before the European Patent Office (EPO) and the US Patent and Trademark Office (USPTO).

However, it has appeared that the standards applied by the competent US courts and the EPO’s boards of appeal regarding patentable subject matter in life sciences have diverged to such an extent that the strategy of filing a single PCT application for regional or national phase entry in both these jurisdictions may no longer be the best option. We provide some examples.

One decision that caused major concerns for those engaged in the patenting of diagnostic tools was Mayo v Prometheus, decided by the US Supreme Court in March 2012. In its decision, the court embarked on assessing patentability of claims protecting a method of optimising therapeutic efficacy for the treatment of an immune-mediated gastrointestinal disorder.

The method comprised the steps of administering a drug to a subject and determining the amount of a metabolite in the blood. The claim stated that an amount of that metabolite below a certain threshold value “indicates a need” to increase the dose of the drug in subsequent administrations (since the treatment was ineffective).

On the other hand, the claim stated that if the amount of the metabolite was increased in the blood beyond a certain level, then this “indicates a need” to reduce the amount of the drug in subsequent administrations (since the drug would generate toxic side-effects).

The court found that the claimed method did not require any action other than determining the correlation between drug administration dosages and metabolite levels in the blood. However, the mere determination of this correlation and/or the determination of the threshold of inefficacy versus harmfulness was found insufficient to impart patentability to the claim, because it merely reflected the discovery of a law of nature independent of human interaction.

The decision highlights the court’s view that merely determining a correlation or measuring a parameter, absent further human intervention, is insufficient to transform unpatentable laws of nature into patent-eligible applications of those laws.

Additionally, the court noted that the remaining steps claimed in the method, even if considered as limitations, would nevertheless be insufficient to impart patentability as they were routine steps known in the art.

It follows that diagnostically valuable findings may not be patentable in the US unless the diagnostic process comprises steps in addition to the step of diagnosis itself. That is, patentable claims will likely require steps actively applying the “laws of nature”, which steps or combinations of steps must additionally be uncommon and/or not merely routine applications of the “laws of nature”.

A different approach

The EPO has a fundamentally different approach to assessing the patentability of diagnostic methods. By virtue of law (previously article 52(4) EPC, now article 53(c) EPC), diagnostic methods practised on the human or animal body are excluded from patentability. Ten years ago, the office’s Enlarged Board of Appeal clarified in its opinion G1/04 that diagnostic methods are excluded from patentability only if they comprise all of the following steps:

Diagnostic methods may therefore be patent-eligible before the EPO if they are practised in vitro using a patient sample, such as a body fluid or tissue sample. Moreover, diagnosis-related methods of data collection or data processing that provide “intermediate findings of diagnostic relevance” may also be amenable to patentability, even if they are practised on the living human or animal body, provided that they do not also claim the making of an actual diagnosis, and provided that they do not fall under the statutory exclusion of surgical methods.

“In contrast to US practice, the EPO does not consider in its patentability assessment that diagnostic methods rely on laws of nature, provided that the claimed methods contain technical features.”

When drafting new applications, methods of data collection should, if possible, already be described and claimed independently from diagnostic methods building on such data collection, since recasting an originally disclosed diagnostic method into a mere data collection method may not be possible during prosecution for lack of support.

Naturally, omitting the actual diagnosis from the claimed method may be a suitable approach for inventions related to imaging or measuring clinical parameters, whereas it might not be feasible in cases where the inventive contribution lies precisely in the correlation of a specific marker with a specific disease or clinical picture.

In contrast to US practice, the EPO does not consider in its patentability assessment that diagnostic methods rely on laws of nature, provided that the claimed methods contain technical features. Whether the claimed combination of features, as long as it satisfies the requirements established in G1/04, is patentable, is then normally a question of novelty, sufficiency of disclosure, and inventive step.

Besides claims directed to in vitro diagnostic methods or data collection and/or processing methods, the EPO also allows purpose-limited product claims directed to a substance or composition for use in a diagnostic method practised on the human or animal body, including the use in any specific diagnostic method, ie, so-called “second diagnostic use claims”.

After Myriad

In June 2013, the US Supreme Court handed down the Myriad decision, which reversed the established practice of the USPTO of granting patents on isolated genomic DNA sequences. The inventors of the underlying patents had found that certain mutations in the coding regions of the BRCA1 and BRCA2 genes were correlated with the likelihood of developing breast or ovarian cancer.

The court found that isolated genomic DNA is indistinguishable from that found in the human body. Thus, the court held that genomic DNA is a product of nature and, therefore, implicitly excluded from patentability according to title 35 of the US Code §101.

The characterisation of the claimed nucleic acid as ‘isolated’, ie, severed from the remainder of the genome, did not help Myriad’s case because the claims focused on the genetic information encoded by the respective genes and did not recite changes to the chemical composition or structure resulting from the isolation of the genes from the genome.

In contrast, cDNA corresponding to the BRCA genes but lacking their non-coding sequences was considered patentable subject-matter because this cDNA does not occur in nature.

In a subsequent decision issued in December 2014, the US Court of Appeals for the Federal Circuit again dealt with different patents of the BRCA gene patent family. The claims at issue related to single-stranded primers hybridising to genomic sequences of the BRCA1 gene and to methods for screening the germline of a human subject for an alteration in the BRCA1 gene.

The federal circuit held that primers did not constitute patentable subject matter for essentially the same reasons that the Supreme Court set forth for genomic DNA in the Myriad case. The patentee, Myriad, argued inter alia that primers were single-stranded DNA molecules and therefore did not occur in nature. Further, their function in a DNA amplification process was argued to be distinct from the protein encoding function of genomic DNA.

But the federal circuit was not convinced by these arguments. The court found that preparing primers amounted to nothing else than severing—albeit short and single-stranded—DNA sequences from their natural surroundings. Therefore, the situation was in essence identical to that previously addressed by the Supreme Court. With regard to the allegedly different function, the federal circuit did not discern any difference between naturally occurring DNA and primers because the function of the primers was identical to that of the natural DNA, ie, to hybridise to their respective complementary strands.

Additional method claims were considered by the federal circuit comprising the steps of comparing wild-type BRCA1 sequences with the sequences of a patient, in particular, to detect mutations. The comparison included either a hybridisation step or a DNA amplification step. The mutations were not specified in the claims, nor was any link to a specific disease recited. These claims were also not regarded as patent-eligible. The court held that the mere comparison, without any further action, relates only to an abstract idea, constituting another implicit exclusion from patent eligibility derivable from 35 USC §101. As the remaining features were considered routine measures, there was no further inventive concept to take the claim into patent eligibility.

Routine features

A further decision that came to essentially the same result as the Supreme Court in Myriad was issued by the US District Court for the District of Delaware in October 2014, called Genetic Technologies v Bristol-Myers Squibb. One of the patents in the case related to a method for detecting alleles of a genetic locus and haplotypes by amplifying genomic DNA with a primer pair spanning a non-coding sequence in genetic linkage with the allele to be detected.

The correlations underlying the patent were characterised by the court as constituting natural phenomena. The remainder of the features were deemed routine, rendering the claims not patent-eligible.

At the EPO, a board of appeal was confronted with very similar arguments from parties that opposed a patent of the Myriad family. Namely, it was alleged that the claimed probes occur in nature and are therefore merely non-patentable discoveries. The board, however, held that the probes had been identified by means of a technical process and so constituted isolated elements of the human body that are patentable in accordance with rule 23e(2) EPC (now rule 29(2) EPC).

In contrast to the position taken by the US courts, it was irrelevant that the sequence of the claimed probes was identical to a part of the naturally occurring sequence of the human BRCA1 gene.

The allowance of patents claiming isolated nucleic acid sequences that occur in nature is standard practice at the EPO and there is no indication available that this practice may change.

It is worth mentioning, though, that the scope of protection conferred by granted European patents claiming isolated nucleic acids has to be determined by the national courts of those EPC contracting states that are also EU member states, in consideration of the case law of the Court of Justice of the European Union (CJEU) on the interpretation of the EU’s Biotech Directive (Directive 98/44/EG).

In its judgment, C‑428/08 – Monsanto v Cefetra, the CJEU dealt with the protection conferred by a product claim of the Dutch part of a European patent directed to a specific isolated DNA sequence and in effect concluded that the claim does not protect a material containing the claimed DNA sequence if the DNA does not perform its function (as disclosed in the patent) at the time of the alleged infringement.

So, while the EPO does allow product claims directed to isolated nucleic acids, the protection actually conferred by such claims seems to be reduced at least in some EU member states to a purpose-limited product protection.

At the EPO, other restrictions to patentability exist in important areas of the life sciences that do not have a counterpart in the USPTO. A prime example is the exclusion from patentability of human embryonic stem cells that we have dealt with previously. In the Brüstle case, the competent Technical Board of Appeal has now confirmed that human embryonic stem cells are not patentable under the EPC. In contrast, there is no exception to patentability for embryonic stem cells according to US patent law and practice.

Similarly, in the field of plant biology, the EPO seems more restrictive in awarding patents than the USPTO. For example, plant varieties are excluded from patentability by law in the EPO, whereas no such restrictions exist in the USPTO. Likewise, when interpreting the scope of exclusion applicable to essentially biological processes for the production of plants, the Enlarged Board of Appeal has taken a rather strict stance, in contrast to the common practice of the USPTO. On the bright side, however, the Enlarged Board of Appeal has now confirmed that plants and plant materials (excluding plant varieties) are indeed patent-eligible, even if they can be produced only by essentially biological processes.

In summary, there are important differences between the EPO and the USPTO in the assessment of patentable subject matter in life sciences. These differences apply, inter alia, to the patentability of nucleic acid sequences, therapeutic and diagnostic methods, human embryonic stem cells and plant breeding methods.

Inventors from Europe may need to think twice in the future before prosecuting patent applications relating, for example, to diagnostically relevant single nucleotide polymorphisms or to novel technical enzymes at the USPTO.

On the other hand, the restrictive position of the EPO with respect to patenting in the field of human embryonic stem cells may deter US inventors from seeking patent protection in Europe. Depending on the technology involved, filing national or regional applications may therefore be a useful and cost-effective alternative to PCT filings.

Joachim Wachenfeld is an attorney at  Vossius & Partner. He can be contacted at: wachenfeld@vossiusandpartner.com

Oswin Ridderbusch is an attorney at Vossius & Partner. He can be contacted at: o.ridderbusch@vossiusandpartner.com